some new rearrangements in nitrogen heterocyclic … · cyclopropenones were not formed ......

Some New Rearrangements in Nitrogen

Heterocyclic Chemistry

A Thesis submitted for the degree of Doctor of Philosophy

in the Faculty of Science

of the University of Leicester

by

MICHAEL YELLAND

December 1968 The University of Leicester

r

UMI Number: U622417

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X V %

statement

The work described in this thesis was carried out by the author in the Department of Chemistry of the University of Leicester under the supervision of Professor C. W. Rees, and is not concurrently being submitted for any other degree.

September 1966 - November 1968 Signed

(M. Yelland)

Acknowledgements

The author would like to express his sincere thanks to the following:

To Professor C. W. Rees for his excellent supervision, constant help, and provision of research facilities.

To Imperial Chemical Industries Limited, Dyestuffs Division, for financial support.

To Mr. M. Jones and Miss E. A. Phillpot for mass spectral and PMR measurements, and to all other members of the staff for their help.

To his wife Mary, for all her cheerfulness and patience during the last two years.

SUMMARY

The oxidation of 3-mono- and 3,M— di-substituted 2-pyrazolin-

5-ones was studied to determine whether the pyrazol-3-one

intermediates generated would decompose with loss of nitrogen to give cyclopropenones. Cyclopropenones were not formed however; this parallels the behaviour of 3-indazolones which had been shown not to give benzocyclopropenone. *+,5-Diphenylpyrazol-3-one lost nitrogen and carbon monoxide to give diphenylacetylene, and nitrogen to give 2,3,6,7-tetraphenylpyrazolo-(l,2a)-pyrazol-l,5- dione. The unstable «-carbonyl-azo intermediates from 2-pyrazolin- 5-ones were trapped with tetracyclone to give stable Diels Alder adducts in good yield. When heated these adducts partly undergo a retro-Diels Alder reaction and partly undergo a novel molecular rearrangement, paralleled in the mass spectrometer, to give carbon dioxide and l,7a-diazaindenes. (This is described in Section 1).

Efforts towards the synthesis of 5,6-diphenyl-1,2,3-triazin-4-one are described since its 3-amino derivative should give

diphenylcyclopropenone on oxidation. Amination of 3,4-diphenyl- 2-pyrazolin-5-one caused ring expansion to 5,6-diphenyl-l,2,3,4- tetrahydro-1,2,U-triazin-3-one, which on oxidation gave 5,6-

diphenyl-1,2,4-triazin-3-one. Amination of the latter caused

ring contraction, however, to give 4,5-diphenylimidazolin-2-one

with hydroxylamine-O-sulphonic acid, and 4,5-diphenyl-l,2,3-

triazole with chloramine. (This is described in Section 2).1-Amino-3,4,5,6-tetraphenyl-2-pyridone was prepared as a

possible precursor to hexaphenyl-l,7a-diazaindene (see above).

When oxidised with lead tetra-acetate it underwent an unusual rearrangement to give 3,4,5,5-tetraphenylpyridazine; evidence for

a nitrene intermediate was provided by oxidation of the ^-aminopyridone in dimethyl sulphoxide when the nitrene was trapped as the sulphoximine. Pyrolysis of this gave the same products as the oxidation reaction. The nitrene formed by oxidation of the hydrazine, and by photolysis of the sulphoximine, was trapped with cyclohexene to give the same aziridine.

By contrast, oxidation of N-aminophenanthridone gave 4,5- benzocoumarin and l-amino-2,3-diphenyl-4-quinolone gave a bis- quinolone. (This is described in Section 3),

The preparation of 2,3 -bis-(m-methoxyphenyl)-cyclopropenone

and the attempted oxidative coupling of this and the bis-phenol to

give the phenanthracyclopropenone system are described in the

Appendix.

Mechanisms are proposed for all the new reactions described.

ContentsPage

Abbreviations 1Experimental Techniques 2Section One. Oxidation of substituted 2-pyrazolin-

5-ones.Introduction: «-Carbonyl-azo compounds 5

Methods of Preparation 5Reactions 9Oxidation of I -simino heterocyclic compounds 15

Experimental: Preparation of ester starting materials 19Preparation of substituted 2-pyrazolin-

5-ones 21Oxidation of 3,4-disubstituted 2-pyrazolin-

5-ones 25Oxidation of 4,5-diphenyl-3-pyrcizolidinone 31 Oxidation of substituted 2-pyrazolin-5- ones in the presence of dienes 32Pyrolysis of Tetracyclone/Pyrazolinone

adducts 36Miscellaneous Experiments 40

Discussion 43

Section Two, Amination of pyrazolones and triazinones

Introduction 68

Experimental 72

Discussion 81

Section Three. Oxidation of N.-aminopyridones.

Introduction: Amino-nitrenes 102

Experimental: Preparation of l-amino-3,4,5,6-tetraphenyl-2-pyridone 119

Oxidations of l-amino-3,4,5,6-tetraphenyl-2-pyridone 123

Pyrolysis of N-(3,4,5,6-tetraphenylpyrid-2-on-l-yl)-dimethylsulphoximine 128Photolysis of the sulphoximine 129l-Amino-4,6-diphenyl-2-pyridone 131l-Amino-4,5,6-triphenyl-2-pyridone 1325-Aminophenanthridin-6-one 134l-Amino-2,3-diphenyl-4-quinolone 136l-Amino-6-methyl-3,4,5-tripheny1-2-pyridone 137 Miscellaneous Experiments 139

Discussion 140

Appendix. Preparation and Reactions of bis-(m-methoxy-phenyl)-cyclopropenone 176

References 195

ABBREVIATIONS

Throughout this thesis the following abbreviations have been used:

DMSO: Dimethylsulphoxide

HOS : Hydroxylamine-O-sulphonic acid LTA : Lead tetra-acetate

Tetracyclone (TO): Tetraphenylcyclopentadienone

Many common inorganic reagents such as hydrochloric acid, magnesium sulphate, and sodium sulphate have been represented by their formulae.

In the Experimental section the nomenclature of compounds complies with that recommended by the Chemical Society. In

other sections, shorter, simpler names have often been used e.g. 5,6-diphenyl-3-oxo-dihydro-1,2,4—triazine is abbreviated to 5,6-diphenyl-l,2,4-triazine-3-one.

Experimental Techniques

1. Infra-red (i.r.) spectra were recorded in the range

4000-650 cm. using a Perkin-Elmer 237 grating spectrophotometer and a Unicam SP-200 spectrophotometer. Spectraof solids were taken as Nujol mulls and liquids as thin films,

using polystyrene as reference.

2. Ultra-violet (u.v.) spectra were recorded in the range 200- 450 my using a Unicam SP 800 recording spectrophotometer. Solutions (in 1 cm. cells) were in absolute ethanol unless

stated otherwise.

3. Proton magnetic resonance (PMR) spectra were taken on a Varian A60 instrument. Solvents used were deuterochloroform and hexadeuterodimethylsulphoxide with tetramethylsilane as internal reference.

4. Mass spectra were taken on an A.E.I. MS.9 instrument. Samples were admitted to the instrument using a direct insertion lock.

Spectra were run at 70 e.v., trap current 100 yA, at as low

a temperature as necessary to give a suitable sample pressure.

5. Thin layer chromatography (TLC) was used extensively as a

qualitative guide during reactions, and for assessing

the purity of compounds. Glass plates coated with Silica

Gel G (E. Merck), and Aluminiumoxid G (Type E, pH 7.5)(E. Merck) were used, and ether/petrol mixtures were

generally used as eluants.

6. Column chromatography was carried out using silica-gel MFC (B.D.H.) and alumina pH7-7.5 [prepared by deactivation of basic alumina (Spence type H) with 10% by weight of 20% acetic acid in a ball-mill for 3 hr.]. The compound to bechromatographed was adsorbed onto the support, from a solvent, by evaporation under vacuum in a rotary evaporator. Columns were packed dry, and eluted with mixtures of petrol and ether containing a gradually increasing proportion of ether. Ether was then gradually replaced by methanol. In all experiments only fractions containing significant amounts of material have been recorded.

7. Dry solvents were prepared as follows:

(a) Methylene chloride was dried by refluxing over calcium hydride, distilled, and stored over molecular selves (type

4A).

(b) Methanol and ethanol were dried by refluxing over

magnesium turnings with a few crystals of iodine. The solvents were distilled from their alkoxides when required.

(c) Anhydrous ether was stored over sodium wire, and finally

dried with a small amount of sodium hydride when used as a

solvent for aminations using chloramine.(d) Dimethyl sulphoxide was dried by storage over

molecular sieves (type 4A).

g Petrol used during this work was light petroleum, b.p.40-60°, unless stated otherwise.

9. Lead tetraacetate (LTA) was commercial material (B.D.H. ) and was dried by suction from the acetic acid, and stored over concentrated sulphuric acid in a desiccator.

10. Melting points (m.p.) were taken on«a Kofler Micro Heating Stage, and are corrected.

11. Hydroxylamine-O-sulphonic acid (HOS) was prepared by the

method^OO of G6sl and Meuwsen and stored in a desiccator.

12. Chloramine was prepared in ether solution by the method^^

of Theilacker and Wegner, giving a chloramine concentration of approx. 0.22 M.

SECTION ONE

Oxidation of substituted 2-pyrazolin-5-ones

Introduction

«-Carbonyl-azo compounds

The chemistry of «-carbonyl-azo compounds containing one

carbonyl function (R-N=N-CO-R', R-N=N-COOR') and two carbonyl functions (R-CO-N=N-CO-R', ROOC-N=N-COOR*) adjacent to the azo

group, has recently been reviewed.^ Particular emphasis has been placed on the enhanced reactivity of the azo group in these compounds compared with that in other aliphatic and aromatic azo compounds.

Methods of Preparation«-Carbonyl-azo compounds are generally prepared by oxidation

of the corresponding hydrazine derivatives. Diethyl hydrazine- N,N'-dicarboxylate is oxidised smoothly to the azo derivative using bromine^ or nitric acid.

EtOOC-N-N-COOEt ------- > EtOOC-N=N-COOEtH H

Cyclic «-carbonyl-azo compounds can also be prepared by this

method. The pyridazin-l,4-diones [(2), A=-CH2 -CH2 -, -CH=CH-] have been prepared** by LTA oxidation of the hydrazino species

[(1), A«-CH2-CH2-, -CH=CH-]:

y( I )

UA ^

2

( 3

^ 3 ,

(4 )Trapping these extremely reactive species with butadiene and

anthracene gives the Diels-Alder adducts (3) and (4). Phthalazin-1,4-dione (6) has been generated^ by oxidation of phthalazhydrazide (5) with LTA, and also by oxidation of the alkali-metal salt of the

hydrazide (7) with t-butyl hypochlorite.

I-H LTA t-BuOCI

(7 )

The stable, highly reactive «-carbonyl-azo compound 4-phenyl-

l,2,4-triazolin-3,5-dione (9) has been obtained? as carmine-red

needles from the oxidation of 4-phenylurazole (8) with t-butyl

hypochlorite in acetone at -50 to -78° and, more conveniently, by LTA oxidation.20 The product can be sublimed, and decomposes without melting at 160 - 180°.

Ph— N I LTA

(8 ) (9)Ullman and Bartkus® generated 3-indazolone (11) by LTA oxidation of 3-indazolinone (10), but attempts to isolate it were unsuccess

ful, polymerisation occurring below 0°.

N-H

(lO) (II)

An uncommon generation of the pyrazol-3-one ring system by dehydrohalogenation of 4-chloro-Z-pyrazolin-5-ones has been

a

reported.9 Treatment of the chloropyrazolone (12) with aqueous sodium hydroxide or with triethylamine in ether gave the unstable pyrazol-3-one (13, R,R'= aryl or alkyl).

A0 2) (13 )

Oxidation of 2-pyrazolin-5-ones substituted in the 3 and/or 4 positions (14) with LTA also gave the pyrazol-3-one system.10

A A

0^) (is)Tautomérisation of (14) to the hydrazino form (15) in solution has been shown to occur11 on the basis of spectral data, and this

species is then amenable to oxidation with LTA.l^ Treatment of the dihydro-oxadiazinone (16) with sodium triphenylmethide causes isomerisdtion to the hydrazino form (17). Oxidation of this species

with LTA has been reported!^ to proceed via the oxadiazinone (18).

_ Ph

( l 8 )

Reactions of «-carbonyl-azo compounds.

(a) Thermal stability»The diesters of azodicarboxylic acid are relatively very

stable to heat and, with care, can be distilled. The cyclic «-carbonyl-azo compounds described above, where the azo group is necessarily cis, are however generally much less stable, and decompose rapidly at temperatures well below 0°, Polymerisation catalysed by radicals generated in the decomposition frequently

occurs. Kealy has reported^ the formation of 1,4,6,9-tetraketo- pyridazino-(l,2a)-pyridazine (19) from decomposition of pyridazin-1,4-dione at about -30°.

V-30 Ay+ N,

(19)

10

Phthalazin-l,4-dione decomposes similarly with the

formation of a polymer which, on heating gave the phthalazino- phthalazine (20) in 66% yield.

(20)This compound was also obtained directly by heating solid phthalazin-1,4-dione.

The fate of the pyrazol-3-one systems Cil3), R=CH3 , R’=H;R=Ph, R’*Ph] in the absence of nucleophiles is uncertain. In the presence of lead salts derived from the LTA oxidant, complexes were obtained^ ® which could be freed from lead by treatment with sulphuric acid in ethanol, or CO2 and water. The resulting orange material when heated, evolved gas and decomposed between 127° and 250°. In the presence of hydroxide ions the species (13) decomposed with loss of nitrogen and formed %,G-ungaturated acids in high

yield by the following proposed mechanism:^

coo Ph COO"

II

This mechanism was considered to be a general one where R and R' * alkyl or aryl.

The 3-indazolone (11) decomposed in a similar way in the

presence of water and methanol to give benzoic acid and methyl benzoate.

The diphenyloxadiazinone (18) is extremely unstable at normal temperatures and decomposes rapidly with loss of nitrogen and CO2 to give tolan (14%).

b■> Ph— C^=G-Ph + N% + C O 2

«-Carbonyl-azo intermediates have also been proposed^® in the oxidation of 4,5-diphenyl-3-pyrazolidinone (21), add trans-

5,6-diphenyltetrahydro-l,3,4-oxadiazin-2-one (23). The former

loses nitrogen and carbon monoxide with the formation of trans- stilbene (22) as shown.

P t ^P,h H

(21)

» > = ( + Na + C(3

(22)

12

The latter fragments similarly to carbon dioxide, nitrogen, and trans-stilbene (90%),

Ph HPh

LTA )N ' 1 ^ / I ' ) -{ + Nz - h COgp f i & N > ^ H Ph

H (23)

Another unusual reaction which apparently involves an «-carbonyl-azo intermediate has been reported^** by Ruhkopf.Oxidation of 4-ethyl-4-phenyl-pyrazolidin-3,5-dione (24) with bromine undergoes an interesting "dimérisation" to form the bicyclic compound(25).

P h y N-HE t \

(b) Addition Reactions.The electrophilic, free radical, and substitutive addition

reactions of «-carbonyl-azo compounds have been comprehensively

reviewed^ by Fahr and Lind, and since they are not directly relevant to the present work, are not described again here.

PK

(25)

15

(c) Reaction with Dienes.

The most outstanding feature of «-carbonyl-azo compounds

is their capacity to behave as extremely reactive dienophiles in1,4-cycloaddition reactions.

Ethyl azodicarboxylate was one of the first dienophiles to be used^S in the Diels-Alder reaction with cyclic and acyclic dienes,

and this reaction provides a convenient method for the preparation of substituted dihydropyridazines.

EtO,C

N^COaEtI

The high reactivity of the cyclic «-carbonyl-azo compounds in these

reactions can be attributed in part to the cis-fused nature of the azo group, which removes any retarding steric factors during the cycloaddition.IG Dienophiles containing N=N bonds are also in O

general more highly reactive than their C=C analogues. On the basis of kinetic measurements the l,2,4-triazolin-3,5-dione

intermediate (9) is the most reactive dienophile known.^ The

unstable species phthalazin-1,4-dione (6)-, 3-indazolone (11) and pyrazol-3-ones (13) have also been shown^s^,10 be very reactive

dienophiles, and the resulting adducts have been obtained in good

14

yields. Carpino obtained cyclopentadiene adduct (26) of the

pyrazol-3-one (13, RaR’aPh) in 71% yield, generating the intermediate by dehydrohalogenation of 3,4-diphenyl-4-chloro-2-pyrazolin-5-one with triethylamine in the presence of an excess of cyclopentadiene.^

»hPhPh

(26)S” +PhCOCHCOiEt MH (29)(28)

Proof of the structure of (26) was obtained by catalytic hydrogenation to give the dihydro species (27) which was synthesised unambiguously from ethyl 2-benzoylphenylacetate (29) and 2,3-diazabicyclo-[2,2,l]-heptane (28).

Gillis and Weinkam recently reported^® trapping various substituted pyrazol-3-ones (13), generated by oxidation of the

corresponding 2-pyrazolin-5-ones, with a variety of dienes.From their results, they conclude that the system (13) is less

reactive than (2), (6) and (9) due to the azo-linkage of the pyrazol-3-ones being less electron poor. The degree of substitution of the 2-pyrazolin-5-one ring did not appear to hinder the

15

oxidation, making this reaction eminently suitable for the preparation of substituted pyrazolo-pyridazinones.

The "trapping" of «-carbonyl-azo compounds with tetracyclone

as diene has not been widely reported. The indazolone (10), and other nuclear substituted indazolones, have been reacted with tetracyclone (30) to form crystalline adducts.

Ph+ Ph

(30)

The use of tetracyclone as the diene component in orthodox

Diels-Alder reactions has recently been reviewed.

Oxidation of N-amino heterocyclic compounds.Oxidation of 3-aminobenzotriazin-4-one (31) with LTA has

been shown to generate benzyne (32), benzocyclopropenone (33) and3-indazolone (34). The presence of these highly reactive species

has been demonstrated by "trapping" experiments with tetracyclone. Benzyne was trapped to form tetraphenylnaphthalene (35), and

benzocyclopropenone gave its hydrolysis product benzoic acid.

16

The 3-indazolone, which was considered to be formed by a

different mechanism to that involved in the benzocyclopropenone

formation, gave an adduct ($6) with tetracyclone identical in all

respects with that formed by oxidation of 3—indaz_olinone (37) in

the presence of tetracyclone.

-NHz UA

H,0aC O z H

IT

Oxidation of the triazinone (31) and 3-indazolinone in

methanol both gave methyl benzoate.In order to prove that benzocyclopropenone was in fact

formed as a result of the triazinone oxidation, the 6- and 7-

chloro-3-aminobenzotriazin-4-ones were each oxidised in methanol.

The products obtained from the 6-chloro isomer (38), methyl m-chlorobenzoate (58.5%) and methyl g-chlorobenzoate (11.5%), indicated that 4-chlorobenzocyclopropenone (39) had been formed and ring opened in two ways under attack by methanol to give a mixture of the isomeric esters. Oxidation of 5-chloro-3-indazolinone (40) in methanol gave only methyl m-chlorobenzoate, thus proving that the methyl g-chlorobenzoate was in fact derived from the methanolysis of the chlorobenzocyclopropenone (39), and

that no cyclopropenone was formed by oxidation of the indazolinone ring system.

N-NH, LTA J. M e O H ^

■ U - OCl(X) (Y)

LTAMeOH •> (x) only

Following from the above observations that the unstable

benzocyclopropenones were formed by the oxidation of 3-amino-

la

benzotriazin-4-ones and not by oxidation of 3-indazolinones,

an investigation into the possible synthesis of stable cyclo-

propenones by oxidation of substituted 2-pyrazolin-5-ones has

now been carried out. The nature of the unstable «-carbonyl-azo intermediates (13) has been investigated by trapping experiments with dienes and alcohols, and some unusual reactions of the Diels-Alder adducts have been uncovered.

19Experimental

Preparation of ester starting materials

1. Ethyl 2-benzoylphenylacetate.

Ethyl phenylacetate (65,6 g., 0.4 mole) in dry ether (65 ml.) was added slowly to a stirred suspension of sodamide (16.4 g., 0.42 mole) in dry ether (45 ml.) at -30® and the mixture was stirred for 5 rain. Phenyl benzoate (43.6 g., 0.4 mole) was then added and the mixture was refluxed for 2 hr. The reaction mixture was then poured into a mixture of ice/water (1 1.) and acetic acid (45 ml.). The aqueous layer was washed with ether (2 x 20 ml.) and the combined ether extract was washed with sodium bicarbonate (2 x 40 ml. 2N), then with water, and dried (MgSO^). The ether solution was evaporated to 50 ml. and petrol was added until a cloudy suspension was obtained. Storage at 0® for 48 hr. deposited ethyl 2-benzoylphenylacetate (25 g., 25%). Recrystallisation from ethanol gave colourless needles, m.p. 86 - 87® (lit‘.°| 87 - 88®).

2. Ethyl 2-benzoyl-3-phenylpropionate.Ethyl benzoylacetate (17 g., 0.09 mole) was added dropwise to

a solution of sodium ethoxide (3.1 g., 0.045 mole) in dry ethanol

(20 ml.) at room temperature, and the mixture was refluxed for 3 hr.

Benzyl bromide (7.7 g., 0.045 mole) was added to the refluxing solution,

and heating was continued for a further 2 hr. when the mixture was

neutral to litmus. After cooling to 20®, the precipitated sodium bromide was filtered off and washed with a little ethanol. The

20

filtrate was evaporated leaving a pale yellow oil, which was washed with hydrochloric acid (20 ml., 2N). The acid layer was

washed with a little ether, which was combined with the oil and

dried (MgSOi ). The oil was distilled to give ethyl 2-benzoyl-3- phenylpropionate (5.2 g., 21%), b.p. 220 - 222°/20 ram. (lit.'°^,

2180/12 mm.).

3. Ethyl 2,4-diphenylacetoacetate.Ethyl 2-phenylacetate (24.6 g., 0.25 mole) in dry ether (35 ml.)

was added dropwise to a stirred suspension of isopropylmagnesium bromide (36.9 g., 0.25 mole) in ether (170 ml.) at 0 - 5°. Gas was liberated and a grey magnesium complex precipitated. The mixture was refluxed for 2 hr., cooled, and poured into water (500 ml.) Sulphuric acid (10 ml., 50%) was added slowly to decompose the mixture, the ether layer removed and washed with sodium carbonate solution (40 ml. 2N), then with water, and dried (MgSOi+).Evaporation of the ether and recrystallisation of the product from ethanol gave ethyl 2,4-diphenylacetoacetate (18.5 g., 86%) as colourless needles, m.p. 78 - 79® (lit.'° , 78®).4. Methyl 2-phenylcinnamate.

A mixture of benzaldehyde (60 ml.), phenylacetic acid (50 g.),

acetic anhydride (40 ml.) and triethylamine (40 ml.) was stirred at

185® for 45 min. then poured into conc. hydrochloric acid (80 ml.).The resulting thick white paste was treated with ether (1 1.) and

21

warmed. Extraction with sodium hydroxide solution (3 x 600 ml.,

4N) followed by acidification with acetic acid gave trans-2-phenyl-

cinnamic acid (59 g., 67%), m.p. 162®. A small sample recrystallised

from ethanol had m.p. 171 - 172® ( l i t 172®).The acid (54.8 g.) was refluxed in thionyl chloride (92 ml.) for

35 min. The excess of thionyl chloride was distilled off under vacuum, and the crude acid chloride poured into methanol (400 ml.). After

heating at 50® for 30 min. the solution was cooled in ice, precipitating methyl 2-phenylcinnamate (46.8 g., 81%). Crystallisation from ethanol gave colourless needles, m.p. 75 - 75.5® (lit/*^, 76.5 - 77.5®).

Preparation of substituted 2-pyrazolin-5-ones.

1. 3,4-Diphenyl-2-pyrazolin-5-one

(a) From ethyl 2-benzoylphenylacetate.Hydrazine hydrate (2.0 g ., 99% solution, 0.04 mole) was

added to a solution of ethyl 2-benzoylphenylacetate (5.0 g.,

0.018 mole) in acetic acid (15 ml.) and the mixture was refluxed for 48 hr. Cooling to 0® deposited 3 ,4-diphenyl-2-pyrazolin-5-one. Recrystallisation from 80% aqueous ethanol gave colourless needles (3.45 g., 81%), m.p. 235 - 236® (lit.79 , 234 - 235®).

(b) From 4,5-diphenyl-3-pyrazolidinone.

The method used was that described by Godtfedson and Vangedal.^ Copper sulphate (1.6 g.) in water (10 ml.) was added

22

over 15 min. to a solution of the pyrazolidinone (1.19 g.) in pyridine (10 ml.) at 0®. After 15 rain, water (30 ml.) was added and the

precipitated solid filtered off and recrystallised from benzene.A second recrystallisation gave colourless needles (0.26 g., 22%), m.p. and mixed m.p. 234 - 235®. An i.r. spectrum was identical with that of a specimen prepared as in experiment 1(a) above.2. 3-Phenyl-4-benzyl-2-pyrazolin-5-one.

A mixture of ethyl 2-benzoyl-3-phenylpropionate (2.82 g.,0.01 mole) and hydrazine hydrate (3.0 g., 99% solution, 0.06 mole) was refluxed (115 - 120® bath) for 31 hr. then kept at 100 - 105® (bath) for 12 hr. The resulting viscous liquid was heated under vacuum at 130 - 140®/15 mm. for 3 hr. and the excess volatile matter distilled off. The residual solid was cooled, and dissolved in sodium hydroxide solution (100 ml., 5%). This solution was diluted

with water (50 ml.) and extracted with ether (2 x 30 ml.). The aqueous solution was then acidified with acetic acid (30 ml.,50% solution) and the pale buff precipitate filtered off, washed

with water and dried in a vacuum desiccator.Recrystallisation from ethanol gave 3-phenyl-4-benzyl-2-

pyrazolin-5-one (1.26 g., 51%) as colourless needles, m.p. 184 - 185® (lit.102 184®).

25

3, 3-Benzyl-4-phenyl-2-pyrazolin-5-one.

A solution of ethyl 2,4-diphenylacetoacetate (9.35 g., 0.04 mole)

and hydrazine hydrate (1.8 g., 64% solution, 0.04 mole) in ethanol

(75 ml.) was refluxed for 24 hr., poured into a dish and the solvent was evaporated off on a steam bath. The residue was heated to 155 - 160° in an open necked flask for 10 min., then dissolved in

boiling ethanol (100 ml.). Water (100 ml.) was added to the hot solution; storage at 0° for 16 hr. gave 3-benzyl-4-phenyl-2-pyrazolin- 5-one (5.5 g., 66%). Crystallisation from ethanol gave colourless needles, m.p. 170 - 172° (lit. *, 172°).

4. 3-Phenyl-2-pyrazolin-5-one.

Hydrazine hydrate (12 g., 99% solution, 0.24 mole) was addedslowly to ethyl benzoylacetate (38.4 g., 0.20 mole) with cooling.

After 1 min. a vigorous reaction occurred and the mixture thickened

as a white solid precipitated. Trituration with ethanol gave 3-phenyl-2-pyrazolin-5-one (27.0 g., 84.3%), m.p. 240 - 242°. Crystallisation from pyridine gave colourless needles, m.p. 243 - 244° (lit. , 244°).

5. Preparation of 4,5-diphenyl-3-pyrazolidinone.

A solution of methyl 2-phenylcinnamate (19.7 g.) and hydrazine

hydrate (6.5 ml., 99% solution) in ethanol (60 ml.) was refluxed for 24 hr., then cooled to 20° and water (60 ml.) was added slowly. The

24

heavy oil which was deposited was extracted with ether (3 x 30 ml.),

and the ether solution was dried (MgSO^). Evaporation of the ether left a semi-solid which, on trituration with benzene (30 ml.) gave4,5-diphenyl-3-pyrazolidinone (13.7 g., 60%) as colourless needles, m.p. 142 - 143° (lit.9 , 134 - 139°).

25

Oxidation of 3,4-disubstituted 2-pyrazolin-5-ones.

General Procedure.

In experiments using lead tetra-acetate (LTA) as the oxidising

agent, the substituted 2-pyrazolin-5-one dissolved in dry methylene

chloride (20 ml. per mmole), was added dropwise over 15 min. to a magnetically stirred solution of LTA (1.2 mmole per mmole of 2-pyrazolin- 5-one) in methylene chloride (50 ml. per mmole of LTA), at room temperature. Stirring was continued until the reaction was complete (TLC). Work-up procedure involved filtering off insoluble residues, evaporation of the filtrate onto a suitable chromatographic adsorbent followed by column chromatography.

1. Oxidation of 3,4-diphenyl-2-pyrazolin-5-one.3,4-Diphenyl-2-pyrazolin-5-one (1.9 g., 8.0 mmole) was oxidised

with LTA in methylene chloride as described above. The solution rapidly turned dark brown, and gas was evolved. Chromatography on silica gel eluting with ether/petrol mixtures gave:(i) Diphenylacetylene (18 mg., 1.3%), m.p. and mixed m.p. 57 - 58°

(lit.lO§ 60 - 61°). I.R. identical to that of an authentic sample.

(ii) Colourless crystals (17 mg.), fluorescent in U.V. light, m.p. 260 - 262°. m/e: 414, 307, 281, 206, 178, 165, 127, 105, 77.

(iii) 2,3,6,7-Tetraphenylpyrazolo-(1,2a)-pyrazole-1,5-dione.

(]36 mg., 7.7%). Crystallisation from ethanol gave colourless needles.

26

m.p. 272 - 274° (Found; C, 81.8; H, 4.5; N, 6.3; m/e 440.

C3 0H20N2O requires: C, 81.8; H, 4.5; N, 6.4%; MW 440).

% a x * 1725; 1635; 1610; 1585; 1515; 1465; 1450; 1390; 1370; 765;750; 723; 715; 690 cm."l.

^max * 262 nm (log e 4.39).m/e: 440 (P), 412 (P-28), 385.78 (metastable), 356 (P-84), 220, 204,

178, 105, 77.

(iv) Further elution with up to 100% ether gave a bright yellow fluorescent compound which could not be purified. Its i.r. spectrum was poorly resolved showing a broad carbonyl peak at 1720 cm.Its mass spectrum suggested that it was polymeric.

TLC of the reaction mixture showed that no detectable amount of diphenylcyclopropenone had been formed.2. Oxidation of 3,4-diphenyl-2-pyrazolin-5-one in the presence of

diphenylcyclopropenone.3,4-Diphenyl-2-pyrazolin-5-one (120 mg., 0.5 mmole) was oxidised

with LTA as in the general procedure, in the presence of diphenylcyclopropenone (103 mg., 0.5 mmole). The reaction mixture was filtered

after 2 hr., and the methylene chloride solution extracted with 65% sulphuric acid (4 x 10 ml.). The acid extract was poured into

ice/water, and the mixture was extracted with methylene chloride (3 X 20 ml.),^washed with water (3 x 10 ml.), dried (MgSOi+), and evaporated to dryness, giving diphenylcyclopropenone (0.098 g.,96%), m.p. 116 - 117° (lit.51, 120°).

27

3. Oxidation of 3-phenyl-4-benzyl-2-pyrazolin-5-one and of

3-benzyl-4-phenyl-2-pyrazolin-5-one.

The pyrazolinones were each oxidised with LTA in methylene chloride

as above. TLC (Silica Gel) examination of each reaction mixture revealed complex mixtures of products. No one product of one

reaction was identical to any of the products of the other reaction.

Purification of the products by column chromatography was unsuccessful.4. Oxidation of 3-phenyl-4-benzyl-2-pyrazolin-5-one with nickel

peroxide in benzene.The pyrazolinone (0.25 g., 1.0 mmole) was dissolved in dry benzene

(50 ml.) at the reflux. After cooling to room temperature, nickel peroxide (0.9 g., 10 mmole) was added. After 2 - 3 min. gases

were evolved and stirring was continued for 2 hr. when reaction was complete. Examination of the reaction mixture (TLC) revealed a complex mixture of products of identical Rf to those produced from

the LTA oxidation.5. Oxidation of 3.y^diphenyl-2-pyrazolin-5-one in methanol.

(a) (i) Using 1.2 equiv. of LTA.

The pyrazolinone (0.5 g., 2-ltnmole) in dry methanol

(50 ml.) was added dropwise to a stirred suspension of LTA (1.2 g., 2.7npole) in methanol ( 100 ml.) at room temperature. The mixture

remained pale yellow during the addition, and was stirred overnight

28

at room temperature. The suspension was filtered, and the

filtrate evaporated onto silica-gel. Column chromatography, eluting with ether/petrol (1 :1 0 ) gave methyl 3-methoxy-2 -phenyl-

cinnamate (0.16 g., 29%), m.p. 81 - 82° (after sublimation)(Found: C, 75.9; H, 6.1; m/e 268. CiyHigOg requires: C, 76.2;H, 6.0%; MW 268).V : 1710 (ester C = 0); 1620 (vinyl ether C=C); 1600; 1580; 1500; 1310; 1300; 1212, 1100 (ester C-O-C); 1070; 1045; 768; 743,712,

698 (monosubst. benzene) cm.PMR: T 6 . 6 8 singlet, (3 protons); 6.60 singlet, (3 protons);2.62 - 2 . 8 multiplet, ( 10 aromatic protons).m/e : 268 (P), 237 (P-OCH3 ), 221, 194, 179, 165, 105, 92, 77.(ii) Using 2.4 equiv. of LTA.

The oxidation was repeated using 2.4 g. ( 54mmole) of

LTA. The yield of 3-methoxy ester was increased to 58%.(b) The pyrazolinone (0.5 g., 21 mole) in methylene chloride

(25 ml.) was added over 15 min. to LTA (1.2 g., 27mmole) inmethylene chloride (25 ml.) at room temperature. Methanol (25 ml.)

was immediately added. The colour of the mixture changed from brown to orange and gas was evolved. After stirring overnight,

the mixture was chromatographed (Silica Gel) to give 3-methoxy ester (0.036 g., 7%), m.p. 80 - 81°. Treatment of the 3-methoxy ester with boron tribromide in methylene chloride gave methyl-2-

benzoylphenylacetate quantitatively as colourless crystals, m.p.

72 - 74° dit.'®^, 74°).

29

6. Oxidation of 1,4-diphenyl-2-pyrazolin-5-one in ethanol.

Oxidation of the pyrazolinone (1.0 g., 42mmole) with LTA

(2.4 g., 5*4mmole) in dry ethanol gave, after chromatography onsilica gel, ethyl 3-ethoxy-2-phenylcinnamate (0.45 g., 36%), m.p.

46 - 48° (Found: C, 77.5; H, 6.8; m/e 296. C1 9H2 0O3 requires:C, 77.8; H, 6.8%; MW 296).V : 1710 (ester C=0); 1630 (vinyl ether C*C); 1600; 1580; 1495;

1440; 1320; 1290; 1215, 1095 (C-O-C); 1070; 1045; 1025; 910; 780,755, 695 (monosubst. benzene) cm.

PMR: T 8.6 - 9.15 multiplet; 5.8 - 6.5 multiplet; 2.65 - 2.95 multiplet, m/e: 296, 267, 251, 206, 178.A repeat oxidation on the same scale using 1.08 mole of LTA increased the yield of the 3-ethoxy ester to 70%.7. Reaction of methyl 2-phenylcinnamate with LTA in methanol.

Methyl 2— phenylcinnamate (0.238 g., 1 mmole) in dry methanol(25 ml.) was added slowly to LTA (Ü.6 g., 1.3 mmole) in methanol (25 ml.). The reaction was stirred overnight at room temperature,

evaporated to dryness, and the ether extracted, to give unchanged

starting material (99%).8. Attempted isomeration of 3,4-diphenyl-2-pyrazolin-5-one.

Sodium triphenylmethide was prepared by the method of Renfrow

and Hauser

50

3,4-Diphenyl-2-pyrazolin-5-one (0.944 g., 4 mmole) was

dissolved in benzene (150 ml.) and a solution of sodium triphenylmethide (2.9 g., 12 mmole) in ether (72 ml.) was added quickly with nitrogen passing over the reaction mixture. After refluxing for 1 hr. the colour of the reaction mixture had changed from red to

pale yellow. The mixture was stood under nitrogen at 25° for 48 hr. and 25 ml. Of the solution was poured into water. The ether layer was washed with water (25 ml.) and the combined aqueous extract acidified with HCl. Precipitation of the starting pyrazolinone (80 mg.), m.p. and mixed m.p. 232 - 233°, (lit.^^, 235°) occurred.

The i.r. spectrum was identical with that of the pyrazolinone.

51

Oxidation of 4,5-diphenyl-3-pyrazolidinone.

1. Alone.

4,5-Diphenyl-3-pyrazolidinone (0.476 g., 2 mmole) in

methylene chloride (5 ml.) was added dropwise to LTA (3.0 g.,

6 mmole) in methylene chloride (15 ml.). Immediate evolution of gas occurred. The mixture was stirred at room temperature for

1 hr., glycerol (Idrop) was added and the insoluble residue was filtered off. The filtrate was evaporated to dryness and ether extracted. Evaporation of the ether gave trans-stilbene (0.26 g., 72%), as rhomboids, m.p. and mixed m.p. 125 - 126° (lit!®®, 124°).An i.r. spectrum was identical with that of an authentic specimen.2. In Methanol.

Oxidation of the 3-pyrazolidinone (0.2 g.) with LTA in methanol gave trans-stilbene (67%) after chromatography, with no evidence of ester products being formed as in the case of 3,4-diphenyl-2-

pyrazolin-5-one.

3. In the presence of Tetracyclone,

Oxidation of the 3-pyrazolidinone with LTA in methylene chloride in the presence of an excess of tetracyclone gave, after

chromatography:(i) trans-stilbene (77%), m.p. 124° (lit}^^124°).

(ii) Unreacted tetracyclone (87%), m.p. 219 - 220°.

52

(iii) 7,8-diphenyl-l,2,3,4-tetraphenyl-l,4-carbono-

pyrazolo-[l,2a]-pyridazin-6-one (1%), m.p. and mixed m.p. 226 - 227°. An i.r. spectrum was identical with that of

an authentic specimen prepared by oxidation (LTA) of 3,4-diphenyl-

2-pyrazolin-5-one in the presence of tetracyclone. (See below).

Oxidation of substituted 2-pyrazolin-5-ones in the presence of dienes.

1. Tetracyclone.(a) 3,4-Diphenyl-2-pyrazolin-5-one (1.5 g., 0.63 mmole) in

methylene chloride (150 ml.) was added dropwise to a stirred mixture of LTA (4.0 g., 0.9 mmole) and tetracyclone (3.5 g., 0.91 mmole) in methylene chloride (150 ml.) over 1 hr. at room temperature.

Stirring was continued overnight, the reaction mixture was filtered, anJ the residue washed with methylene chloridè. The filtrate was

evaporated onto silica-gel and chromatographed. Unreacted tetra

cyclone (1.40 g., 40% recovery) was eluted with ether/petrol (1:20).The adduc t(62?lcharacterised as 7,8-diphenyl-l ,2,3,4-tetraphenyl-

1,4-carbono-pyrazolo-[1,2a]-pyridazin-6 -one (I), was eluted with ether/petrol (1:4) and recrystallised from benzene as pale yellow

needles, m.p. 227.5 - 228.5° (Found: C, 85.0; H, 4.9; N, 4.5;

55

m/e 618. C4 4H3 QN2O2 requires: C, 85.4; H, 4.9; N, 4.5%; MW 618).V : 1715, 1605 (C=0); 1590; 1570; 1495; 1340; 1150; 900; 860;

778; 740, 730, 690 (ménosubst. benzene) cm.PMR: T 2.3 - 3.3 broad multiplet, aromatic protons only, m/e: 618 (P), 574 (P-CO2 ), 384 (Tetracyclone), 178 (Tolan).

(b) 7-Benzyl-8-phenyl-l,2,3,4-tetraphenyl-l,4-carbono-pyrazolo-Çl , 2a]-pyridazin-6-one was similarly prepared from 3-phenyl-

4-benzyl-2-pyrazolin-5-one and tetracyclone. The adduct (53%) recrystallised from benzene, gave pale yellow needles, m.p. 174 - 175° (Found: C, 85.3; H, 5.0; N, 4.4; m/e 632. C4 5H3 2N2O2 requires C, 85.4; H, 5.1; N, 4.4%; MW 632).V : 1730, 1625 (C=0); 1590 (C=C); 1500; 1350; 1160; 980; 780; 760; 730, 705, 695 (monosubst. benzene) cm.

PMR: T 8.7 - 8.93 multiplet, (2 protons, CH2 ); 2.65 - 2.95 (30 aromatic protons).

m/e: 632 (P), 588 (P-CO2 ), 384 (Tetracyclone).

(c) 8-Phenyl-1,2,3,4-tetrapheny1-1,4-carbono-pyrazolo-[1,2a]-pyridazin-6-one similarly prepared from 3-phenyl-2-pyrazolin-5-one and

tetracyclone, was recrystallised from benzene/petrol (1 :1 ) to give yellow needles (63%), m.p. 222.5 - 223° (Found: C, 85.3; H, 4.8;

N, 5.2;m/e 542. C3 8H2 6M2O2 requires: C, 84.1; H, 4.8; N, 5.2%

54

MW 542).

V : 1740, 1570 (C=0); 1600 (C=C); 1500; 1440; 1150; 975; 930;745; 700; 690 cm."^.

PMR: T 4.03 singlet,(1 proton); 2.1 - 3.35 broad multiplet,(25 aromatic protons).

m/e: 542 (P); 514 (P-CO), 498 (P-CO2 ), 384 (Tetracyclone).

Alternative synthesis of adduct (I) (See experiment 1(a)).

4-Chloro-3,4-diphenyl-2-pyrazolin-5-one was prepared by the method of Carpino, Terry and Thatte.® 4,5-Diphenyl-3-pyrazolidinone

(2.0 g.) was suspended in nitromethane (15 ml.) and chlorine was bubbled through the mixture. After 1 min. the pyrazolidinone dissolved, the solution became hot, and a solid began to precipitate. After 5 min. this solid dissolved, and in another 2 min. another solid precipitated. The chlorination was stopped at this point

and the mixture transferred to a dish to allow the solvent to evaporate. The residue, a tarry solid, crystallised from nitromethane to give 4-chloro-3,4-diphenyl-2-pyrazolin-5-one (0.5 g., 24%), m.p. 171 - 172° (lit.® , 171.8 - 173.8°). The chloropyrazolone (0.27 g., 1 . 0 mmole) and tetracyclone (0.96 g., 2-5 mmole) were

suspended in dry ether (50 ml.) at 0°. Triethylamine (0.15 ml.,

15 mmole) was added, and the mixture was stirred at 0° for 3 hr.

The insoluble residue was filtered off, washed with ether and then

35

with water giving unchanged tetracyclone (0.42 g.), m.p. 218 - 220°.

The filtrate was evaporated onto silica-gel and chromatographed. Benzene/petrol (1:3) eluted tetracyclone (0.1 g., total recovery = 54%). Benzene/petrol (10:1) eluted 7,8-diphenyl-l,2,3,4-tetraphenyl-l,4-carbono-pyrazolo-[l,2a]-pyridazin-6-one (0.27 g., 44%),

m.p. 226 - 227°, mixed m.p. 225 - 226°. An i.r. spectrum was identical with that of a specimen prepared from 3,4-diphenyl-2- pyrazolin-5-one and tetracyclone as in example (a).

2. Buta-l,3-diene.3,4-Diphenyl-2-pyrazolin-5-one (1.18 g., 5 mmole) in methylene

chloride ( 2 0 ml.) was added dropwise at 0° to a stirred suspensionof LTA (3.5 g., 7.5mmole) in methylene chloride (50 ml.) throughwhich a slow stream of butadiene was bubbling. The mixture wasstirred at 0 ° for 1 hr., then filtered, and the filtrate evaporatedto dryness. The sticky residue was extracted with ether, which onevaporation gave 7,8-diphenyl-pyrazolo-[l,2aJ-pyridazine (0.65 g.,

45%). Recrystallisation of the adduct from benzene/petrol gave9pale yellow needles, m.p. 186 - 187° (lit. , 187 - 189°)

(Found: C, 79.1; H, 5.7; N, 9.8. Calc, for CigHieNaO: C, 79.2;H, 5.6; N, 9.7%).

V : 1670, 1640 (C=0); 1600 (C«C), 1400; 1290; 1260; 1220; 1170;

1080; 990; 980; 925; 785; 770; 740, 700, 655 (monosubst. benzene) cm. PMR: I 6.23 broad peak, (2 methylene protons); 5.61 broad peak.

-1

36

(2 methylene protons); 2.62 multiplet, (10 aromatic protons).X : 210 (loge 4.34), 300 nm (4.00). max. °

Pyrolysis of Tetracyclone/Pyrazolinone adducts.

1, Tetracyclone/3,4-diphenyl-2-pyrazolin-5-one adduct.(a) The adduct (200 mg.) was sublimed at 210°/0.1 mm. for

16 hr. Tolan (3 mg., 4%), m.p. and mixed m.p. 58 - 59°, was collected from the walls of the tube. The remaining sublimate was chromatographed on silica-gel to give;

(i) Tetracyclone (43 mg., 35%), m.p. and mixed m.p. 218 - 220°.

(ii) 2,3,4,5,6,7-Hexaphenyl-[l,7a]-diazaindene (65 mg., 35%) as colourless crystals, m.p. 272.5 - 273.5° (Found:

C, 90.2; H, 5.1; N, 4.9; m/e 574. C43H3 0N2 requires :C, 89.9; H, 5.2; N, 4.9%; MW 574).V : 1610 (C=N); 1575, 1490 (aromatic C=C); 1062;

1020; 773, 753, 700 (monosubst. benzene) cm.

Xmax (dioxan): 258 (log c 4.43), 274 (4.43), 325 nm (3.60) PMR: T 2.5 - 3.1 multiplet, (aromatic protons only),

m/e: 574 (P), 471 (P-CeHgCN).

(b) The adduct (0.1 g.) was stirred in £-dichlorobenzene (2 ml.) at 180° for 2 hr. TLC indicated that decarboxylation of the adduct was occurring. After 28 hr. approximately 40% of the adduct had

37

decomposed to give tetracyclone and the hexaphenyl-diazaindene.There was no evidence (TLC) that a decarbogylated product had been

formed.(c) Decarboxylation of the adduct in 1,2,4-trichlorobenzene

at 220° was complete after 4 hr. The reaction mixture was cooled and poured into ether. The precipitated solid was recrystallised from benzene to give the hexaphenyl-diazaindene (45%), m.p. and

mixed m.p. 272 - 273°.2. Tetracyclone/3-phenyl-4-benzyl-2-pyrazolin-5-one adduct.

The adduct (200 mg.) was sublimed at 230°/0.1 mm. for 16 hr. Chromatography of the sublimate on silica-gel gave:

(i) Tetracyclone (50 mg., 41%), m.p. and mixed m.p.218 - 219°.

(ii) 3-Benzyl-2,4,5,6,7-pentaphenyl-[l-7a]-diazaindene

(50 mg., 27%) as colourless crystals, m.p. 204 - 205° (Found: C, 89.5; H, 5.5; N, 4.7; m/e 588.

C4 4H3 2N2 requires: C, 89.8; H, 5.4; N, 4.8%; MW 588).

% a x ’ 1610 (C=N); 1580 (aromatic C=C); 1525; 1500; 1440; 1075; 1030; 775, 760, 745, 710, 695 (monosubst.

benzene) cm.

m/e: 588 (P), 511 (P - CeHg), 498 (P - C6H5CH2 ).

3, Tetracyclone/3-phenyl~2—pyrazolin-5-one adduct.

The adduct (0.5 g.) was heated at 260° (bath). The solid

38

melted, slowly turned red, and began to bubble as gas was evolved.

The gas was passed through fresh limewater which turned milky after

a few seconds. After 1 hr. the residue was chromatographed on

silica-gel to give:(i) Tetracyclone (120 mg., 34%) m.p. 218 - 220°.(ii) 2,4,5,6,7-Pentaphenyl-[l-7a]-diazaindene (183 mg.,

44%). Recrystallisation from benzene/petrol (1:5) gave colourless powdery needles, m.p. 300 - 301°

(Found: C, 88.9; H, 5.2; N, 5.6; m/e 498. C3 7H26N2

requires: C, 89.1; H, 5.2; N, 5.6%; MW 498).

^max * 1G05 (C=N); 1580 (aromatic C=C); 1535; 1490; 1275; 1080; 1030; 765, 750, 705, 695 (monosubst. benzene) cm.

^max. * 286 (loge 4-47), 324nm. (4*00).PMR: T 3.3 singlet, (1 aromatic proton); 3.1 singlet,

(10 aromatic protons); 2.65 - 2.8 multiplet, (15

aromatic protons).m/e: 498 (P), 394 [P-(H, CgHsCN)], 317, 289, 248,

202, 200, 199, 181, 131, 103 (CsHgCN).

withA repeat experiment^adduct (1.8 g.),also gave pentaphenylbenzene

(105 mg., 7%) after chromatography. The compound, colourless crystals, had m.p. 248 - 249° (lit^09^ 246°) (Found: C, 94.4; H, 5.9; m/e 458.

Calc, for C3 6H2 6 : C, 94.3; H, 5.7%; MW 458).

39

V : 1600, 1575 (aromatic C=C); 1490; 1080; 1035; 907; 780; max ' ' ' '766; 730; 700 cm.“ .

PMR: T 2.4 singlet, (1 aromatic proton); 2.84 - 3.1 multiplet,

(25 aromatic protons).Photolysis of Tetracyclone/3,4-diphenyl-2-pyroazolin-5-one adduct.

Photolysis of the adduct (0.618 g., 1 mmole) in a quartz tube using a 100 watt Hanovia high pressure mercury lamp, using benzene as solvent, for 8 hr. gave after chromatography on silica-gel:

(i) Tetracyclone (12 mg.), m.p. 215 - 217° (lit.‘®*, 220°) after sublimation.

(ii) A yellow solid (300 mg.) containing many compounds which could not be separated. The presence of hexaphenyldiazaindene was indicated by TLC.

40

Miscellaneous Experiments

1. Attempted decarbonylation of Tetracyclone/4,5-diphenylpyrazol-3-one adduct.

The adduct (0.2 g.) was dissolved in benzene and tris-(triphenyl phosphine)-chlororhodium-(I) ^‘♦(0.1 g.) was added. After refluxing

for 16 hr. TLC indicated that no reaction had occurred. Starting material (95%) was recovered from the reaction mixture.

A similar experiment in o-dichlorobenzene at 120° for 6 hr.yielded starting material and a trace of hexaphenyldiazaindene only.

2. The adduct (0.2 g.) was dissolved in ethyl cellosolve (10 ml.)and sodium hydroxide (5 ml., 30% solution) was added. Afterstirring overnight at 100°, dilution of the reaction mixture gave unchanged adduct only.

3. Attempted oxidative degradation of 2,4,5,6,7-pentaphenyl diazaindene(a) KMnOtt

The diaza-indene (50 mg.) was dissolved in refluxing acetone and a solution of potassium permanganate (0.14 g.) in water (5 ml.) was added over 30 min. After refluxing for 4 hr. the

mixture was filtered. Unreacted starting material (80%) was isolated

from the filtrate. No other product could be detected (TLC).

41

(b) Chromic Acid.

Attempted oxidation of the diaza-indene with chromium trioxide

in acetic acid at 55® for 20 hr. gave unchanged starting material

(50%) and an intractable inorganic chromium complex. No degradation

products could be isolated.

4. Bromination of 2,4,5,6,7-pentaphenyldiazaindene.The diazaindene (50 mg.) was dissolved in ethyl cellosolve/acetic

acid (1:1, 20 ml.), and bromine (1 drop) was added. After 16 hr. water (5 ml.) was added and slow crystallisation of 3-bromo-2,4,5,6,7- pentaphenyldiazaindene (48 mg., 84%) occurred. The product, colourless cubes, had m.p. 302 - 303° (Found: C, 77.0; H, 4,5;N, 4.9 ; m/e577(Br60)c3 7H2 gN2Br requires: C, 77.0; H, 4.3; N, 4.9%;MW 577).

\ax ' IGOO (C*N); 1590 C*C); 1475; 1270; 1070; 1025; 770; 750; 710; 700 cm.

PMR: T 3.1 singlet, (10 aromatic protons); 2.72 multiplet, (15

aromatic protons).m/e: 578(Br 8l),576(Br 79),532,498,595,219,178.

5. Photolysis of 2,3,4,5,6,7-hexaphenyl-[l,7a]-diazaindene.

The diazaindene (23 mg.) was photolysed in a pyrex tube using

a 200W Mercury vapour lamp, with benzene as solvent, for 7 days.The resulting brown solution was diluted with petrol giving a dark

42

brown solid. The solvent was evaporated to dryness and the

residue sublimed at 150°/0.1 mm. The sublimate (3 mg.) m.p. 119°

had an identical i.r. spectrum to that of benzoic acid. A mixed m.p. showed no depression.

43

Discussion

As described in the introduction, benzocyclopropenone has

been proposed as an intermediate in the oxidative fragmentation

of 3-amino-l,2,3-benzotriazin-4-ones.l7 This was based on results with substituent-labelled triazinones, where the direction of ring-opening of the benzocyclopropenone has been determined.Thus, 3-amino-6-chlorobenzotriazin-4-one when oxidised in methanol gave a mixture of methyl m- and p-chlorobenzoates. 3-Amino-7- chlorobenzotriazin-4-one when oxidised in methylene chloride,and moist ether was added to the solution, gave a mixture of ra- and £- chlorobenzoic acids. The oxidation was shown not to proceed through an indazolone intermediate, by trapping this highly reactive species

with tetracyclone as it was formed. 3-Indazolinone itself was shown noÿ to give benzocyclopropenone by a similar series of

labelling experiments.In order to determine whether oxidation of the five-membered

2-pyrazolin-5-one system would give stable cyclopropenones by a

stepwise loss of nitrogen from the unstable species (3a)followed

by ring closure of the fragment (4), four aryl-substituted 2-

pyrazolin-5-ones (1) were prepared, and oxidised with LTA.

R v — !i-R' R\ xR' R./-----\ LJA ^

H A( I ) (2 ) (3a) (4 ) (5 )

44

The existence of the hydrazino form (2) of 3- and 4-

substituted 2-pyrazolin-5-ones in solution has been demonstrated

by Katritzky and M a i n e , a n d oxidation of hydrazides with LTA has been shown*** to give the corresponding azo compounds in

high yields.In order to discover whether an unstable cyclopropenone was

formed in these reactions and had ring-opened to give otherproducts, two pyrazolinones were prepared where the 3- and 4-substituents in one (1; R=Ph, R'=PhCH2 -) were the same as the 4- and 3- substituents in the other (1; R=PhCH2 -, R’=Ph), thus any common products in the two reaction mixtures would have arisen through an identical intermediate in both cases, which would be highly indicative that a symmetrical intermediate, presumably the cyclopropenone

(5; R=Ph, R’=PhCH2 “), had been formed at some stage.Before this work was started, Carpino^ generated 4 ,5-diphenyl-

pyrazole-3-one (3) by dehydrohalogenation of 4-chloro-3,4-diphenyl-

2-pyrazolin-5-one with aqueous sodium hydroxide. This highly reactive intermediate was attacked by hydroxide ion with loss of

nitrogen to give a mixture of cis- and trans-cinnamic acid. When the chloropyrazolinone was treated in ether with triethylamine, the

intermediate (3) could be trapped with dienes.

45

fH^^^)==OorEtjN -N i \:O j4 Ph

H (3 )

No information was given about the fate of (3) in the absence of nucleophiles or dienes. In later work,^® Gillis and Weinkham were unable to isolate any identifiable products from its decomposition, and this has also been supported by Kent andAnselme?? and by Carpino.??

In the present comprehensive study of this system, and of the related 4,5-diphenyl-3-pyrazolidinone, more information

concerning the reactions of these unstable «-carbonyl-azo species

has come to light.

Preparation of substituted 2-pyrazolin-4-ones.

3-Phenyl-4-benzyl-2-pyrazolin-5-one (la), 3-benzyl-4-phenyl-

2-pyrazolin-5-one (lb), and 3-phenyl-2-pyrazolin-5-one (Ic) were9,78

all prepared according to literature methods by reacting the appropriate B-ketoester with hydrazine hydrate.

46

R-C0-CH.C02Et + N 2 H 4

(la) R = Ph, R'= PhCH2-

(Ib) R = PhCH2-, R'= Ph(Ic) R = Ph, R ’= H

3,4-Diphenyl-2-pyrazolin-5-one was unknown prior to 1961, when it was synthesised by Grtinanger and Finzi^^ by reacting ethyl-2-benzoyphenylacetate with hydrazine hydrate in refluxing acetic acid for 2 days. Following their method, the pyrazolinone was prepared in 81% yield.

PhPh N2H4 .H2O

PhCOCH.CO^Et a^oH/2 days

This compound was of particular interest to us, as the well

authenticated diphenylcyclopropenone would have been easily detected had it been formed during the oxidation.

An alternative synthesis of this pyrazolinone made use of a

method developed by Godtfedson and Vangedal in which 5-phenyl-

3-pyrazolidinone (6 ) was oxidised to 3-phenyl-2-pyrazolin-5-one (7) with copper sulphate in aqueous pyridine.

47

Phv PhI \_r\ CuSO* , //

aq.pyridineA A(6) (7)

4,5-Diphenyl-3-pyrazolidinone (8 ) when oxidised with this

reagent gave the pyrazolinone (9) in 22% yield.

PhIN ^ h

A(8 ) 9

4;5-Diphenyl-3-pyrazolidinone (8 ) itself was prepared by a variation of Carpino’s method,^®^by refluxing methyl 2-phenyl-

cinnamate with hydrazine hydrate in ethanol.

Oxidation of substituted 2-pyrazolin-5-ones.

Since this work was completed, two papers have appeared describing

the oxidation of 2-pyrazolin-5-ones. According to Gillis and

Weinkham^® the oxidation proceeds without gas evolution, and

gives no identifiable products. The reaction was shown to give

the a-carbonyl-azo intermediate initially, and reactions of this

48

with dienes were carried out. The validity of these results for 3,4-diphenyl-2-pyrazolin-5-one is, however, in doubt as their pyrazolinone had a melting point 40° below the literature value,

to which no reference was made.

Kent and Anselme?? found that oxidation of 3-phenyl-2-pyrazolin-

5-one with mercuric oxide gave, as the only product, a white, highly insoluble solid m.p.>300°, possibly a mercury derivative of the starting material. A mercury derivative of this compound has previously been r e p o r t e d . 1^4

In our hands, when a methylene chloride solution of the3,4-diphenyl-2-pyrazolin-5-one (9) was added to a stirred solution of LTA in methylene chloride gas evolution was observed, and chromatography of the mixture gave four products. Diphenylacetylene (1.3%) was isolated, and had presumably resulted from concerted loss of nitrogen and carbon monoxide from the initially formed oc-carbonyl-azo species (3), since diphenylcyclopropenone was

completely stable under the reaction conditions.

Ph

(9 )

PhLTA

3

Ph-C=C-Ph +Ni +CO

49

This is somewhat analogous to the known fragmentation of

5,6 -diphenyl-l,3 ,^-oxadiazin-2-one (1 0 ) to tolan, nitrogen and carbon dioxide reported by Rosenblum.^^

Ph, _I I > Ik A ------ ^ Ph-CsC-Ph

Ph-ivvN/Ns Ph-^N^ +Ni+COz^ (IC)

Also isolated from our oxidation were colourless crystals, m.p. 262-263°, in insufficient quantity for analytical purification.The mass spectrum, however, gave a molecular weight of 414, and contained large peaks at 206 (diphenylcyclopropenone) and 178 (tolan). The break-down pattern suggested that this compound was either tetraphenylhydroquinone or tetraphenylcatechol. The former has been reported®^ by Eistert and Langbein and has m.p. 311-313°.The latter (11) has recently been obtained^by the dimérisation of diphenylcyclopropenone in the presence of cyclopentadienyl- magnesium bromide or sodium analgam in n-propanol/acetic acid; tetracyclone (13) and tetraphenyl-g-benzoquinone (12) were also

isolated.

50

Ph Ph

The melting point of (11) is given as 252.6-253.7°.

Tetraphenyl-£-benzoquinone (12) and tetraphenyl-o^benzoquinone could arise by dimérisation of the fragment (14) which would result from stepwise loss of nitrogen from (3).

P h PhPh

(3) (14)However, it is difficult to see how the o^quinone could be reduced to the catechol (1 1 ) under such powerful oxidising conditions as those used, unless protonation of the species (14)

occurs before dimérisation, and the catechol (1 1 ) is reasonably stable to oxidation.

The major identified product of the oxidation (7.7%) was

51

characterised as 2,3,6,7-tetraphenylpyrazolo-(l,2a^-pyrazol-1,5-dione (15) on the basis of analytical data and comparison

of spectral properties with those of the known indazolo-(2 ,la)- indazol-6,12-dione (16) reported by Gibson et al.®^ This

latter compound was also formed in small yield by oxidation of 3-aminobenzotriazin-4-one with LTA.^®

N-NHa. LTA ,

y A

V

The mass spectrum of the tetraphenyl derivative showed the initial

loss of a fragment m/e 28 (CO) from the parent ion (m/e 440) with a corresponding metastable peak at 385,78. The rest of the breakdown pattern was similar to that reported for the indazoloindazolone, showing loss of three fragments of m/e 28 (CO and N2 ) with large peaks for diphenylcyclopropenone (206) and diphenylacetylene (178).

The structure of this compound is of similar type to those

obtained by Kealy® from pyridazin-3,6 -dione and phthalazin-l,4-dione and by Ruhkopf^^ by bromination of the ethylphenylpyrazolidindione

52

(see Introduction). The mechanisms by which they are formed are

presumably similar. In the case of (15) this appears to involve

a 1,3-cyclo addition of the fragment (14), formed by loss of

nitrogen from the «^carbonyl-azo species (3), with an intact molecule of (3).

Ph

Ph3) (14)

(15)

The nature of (14) is unknown, though it is shown as a diradical. Whatever the detailed mechanism of the formation of (15) is,

it almost certainly involves a nitrogen-free intermediate like (14), and the occurrence of this intermolecular reaction again

demonstrates the reluctance of (14) to collapse to diphenylcyclopropenone, in spite of the stability of the latter.

1,3,3-Trimethylcyclopropene (18) has recently been isolated^ from photolysis of 3,5,5-trimethylpyrazolenine (17).

CH 3.CH3h"

CH,(17) 04,

(18)

53

Benzocyclopropenes are similarly formed^from the

corresponding indazoles:

Ç H 3

R=CN,COOCH3,OCH3.Therefore, by analogy, the presumed diradical species (14),

and the indazolone analogue may ring close to the cyclopropenones if generated under photolytic conditions.

The main reaction product was similar to that described^® by Gillis and Weinkham, and was a yellow fluorescent solid which

could not be crystallised. Its i.r. spectrum was poorly resolved with a broad carbonyl peak at 1720 cm. The mass spectrum of this compound showed no parent ion, the only significant peak being at m/e 178 (tolan), indicating that this compound is a

polymer.When 3-phenyl-4-benzyl-2-pyrazolin-5-one and 3-benzyl-4-

phenyl-2-pyrazolin-5-one were each oxidised under similar conditions, no evidence was found that the oxidations had gone through the

same intermediates. Complex mixtures, which could not be separated

by chromatography, were obtained from both experiments.

54

When 3 ,M—diphenyl-2-pyrazolin-5-one (9) was oxidised with 1.2 equivalents of LTA in methanol, gas was evolved, and methyl 3-methoxy-2-phenylcinnamate (22, 29%) was isolated. When

2.4 equivalents of LTA were used, the yield of ester increased to 58%. The geometry of this compound is not known with certainty,

but is assumed to be as shown, by comparison with 2 -phenylcinnamic acid, the more stable form of which has the cis-diphenyl configuration,

Ph PhLJA

9 ) 3

Phv f h( Æ i T ^ C O C H j

(22)

Some indication of the instability of (3) was gained by adding methanol immediately after the oxidation of (9) in methylene chloride. The yield of 3-methoxyester fell from 29% to 7%, due presumably to rapid decomposition of the intermediate.

The mechanism proposed for this reaction must accommodate the

use of 2 mole equivalents of LTA per mole of pyrazolinone. Attack

of methanol on the initially formed «-carbonyl-azo species (3)

followed by ring-opening, would give the diazo-compound (24)

stabilised by addition of a second molecule of LTA. This can then be attacked by methanol, eliminating nitrogen and forming the

3-methoxyester (22).

55

OCHjPh\/ /Ph Ph\____/3h

< ^ c (24) (22)

The structure of the ester, previously unknown, was confirmed

by déméthylation with boron tribromide in methylene chloride. The3-hydroxy ester (25) rapidly ketonised to methyl 2-benzoylphenylacetate (26) which was formed quantitatively.

P \ ^ BBr, ^ ___(PhdcH j b opH j OH h opH î O CO^Hj

(25) (26)

When the pyrazolinone was oxidised in ethanol a similar reaction

occurred, and with 2 equivalents of oxidant, ethyl 3-ethoxy-2- phenylcinnamate was formed (70%).

The reaction with methanol was shown not to involve formation of methyl 2-phenylcinnamate as this was inert to the reaction

conditions.

Ph Ph UA)C|I-IjOH Ph\ JFh

56

It is interesting to note that in the oxidation of 3-amino-

benzotriazin-4-one none of the corresponding product, methyl-o-

methoxybenzoate was reported.

Oxidation of 2-pyrazolin-5-ones in the presence of dienes.

The high reactivity of the pyrazolone ring system as a dienophile in cycloaddition reactions has been utilised extensively by Gillis and Weinkham^ ® to prepare adducts of the pyrazolopyridazinone type by generating the pyrazolones oxidatively from pyrazolinones in the presence of a wide variety of dienes. In almost all cases, high yields of adducts were obtained. The butadiene adduct (27) was not prepared by them, but had been reported^ earlier by Carpino who trapped 4,5-diphenylpyrazol-3-one (3), generated by dehydrohalogenation of 4-chloro-3,4-diphenyl-2-pyrazolin-5-one with

triethylamine in ether, with butadiene.

PhPh^ U - A

Ph

(27)

Oxidation of 3,4-diphenyl-2-pyrazolin-5-one with LTA in

methylene chloride in the presence of butadiene gave the adduct

57

(27, 45%) with properties identical to those reported by Carpino.

Previous workers^^*^® in this department had obtained good yields of crystalline adducts when 3-indazolinone or 3-amino-

benzotriazin-4-one were oxidised in the presence of tetracyclone (see Introduction), and it was therefore of interest to determine whether the pyrazol-3-one system could be similarly trapped,

3,4-Diphenyl-2-pyrazolin-5-one (9), 3-phenyl-4-benzyl-2- pyrazolin-5-one (la), and 3-phenyl-2-pyrazolin-5-one (Ic) were each oxidised with LTA in methylene chloride in the presence of an excess of tetracyclone. Good yields of the pale yellow adducts (28) were obtained in each case.

TCPh

(28)

Compound (28, R=R'=Ph) was also synthesised by dehydrohalogenation of 4-chloro-3,4-diphenyl-2-pyrazolin-5-one with triethyl

amine in the presence of tetracyclone.

The mass spectrum of each adduct showed well defined peaks for the parent ion and tetracyclone (m/e 384), but in each case the

58

first major fragment lost from the parent ion had m/e 44, suggesting that carbon dioxide was being lost. In view of the structure (28) this was very intriguing, and it was considered

of interest to see if the same reaction occurred on pyrolysis,

since this sometimes parallels mass spectral fragmentation.When the adduct (28, R=R’=Ph) was sublimed at 210®/0.1 mm., it gave tolan (4%), tetracyclone (35%) and a colourless crystalline compound (35%), highly fluorescent in u.v. light, which from spectral and analytical data was assigned the hexaphenyldiazaindene structure (29). '

Ph

Ph,

Ph

Ph

PhPh

(29)Ph-

+ Ph-CsC-Ph

Tolan and tetracyclone had presumably arisen from a retro-Diels Alder reaction; again tolan is formed in only low yield from the

«-carbonyl-azo intermediate (3).

Phv fh Phv ^

P h - ^

59

The parent ion in the mass spectrum of the diazaindene

coincided exactly with the P-44 peak observed in the mass spectrum

of the adduct. That carbon dioxide was evolved thermally, was

proved by passing the gases from the thermolysis of adduct (28, R=Ph, R*=H) through fresh limewater, which rapidly became milky. Carbon monoxide was also detected by burning the evolved gas. In this example, tetracyclone (34%) was recovered and the pentaphenyldiazaindene (30, 44%) was obtained.

Ph

Ph

Ph

PhPh

Ph(30)

Ph-CO

Ph Ph

(31)In a larger scale experiment, pentaphenylbenzene (31, 7%) was

also isolated; its formation is most reasonably explained by reaction between the tetracyclone and phenylacetylene formed during thermolysis, as shown. In the PMR spectrum of (30) the

proton in the 3-position showed clearly as a singlet at t 3.3.

60

In the unsubstituted diazaindene the proton at position 3 appears

at T 3.62; these values.are in good agreement, when allowance is made for the expected chemical shift down-field for the proton adjacent to a phenyl group. Electron-density calculations by Paudler and Dunham,confirmed by bromination of the diazaindene

(32), have predicted the high reactivity of the proton in the 3- position to electrophilic substitution. Thus bromination of (32) with bromine water gave a monobromo derivative (33), and the peak

in the PMR spectrum due to this proton disappeared.

^ cd>(33)

WCO(32)

Bromination of the diazaindene (30) in ethylcellosolve/acetic

acid gave a crystalline monobromo derivative (34). In the PMR spectrum the peak due to the proton at position 3 had disappeared,

(30)Ph

Ph

(34)

61

Similarly the diazaindene (35, 27%) and tetracyclone (41%)

were obtained when the adduct (28; R=Ph, R'=PhCH2 -) was sublimed.

Ph

Ph(35)

R =Ph R'=OI*Ph

Attempts to decarbonylate the adducts (28) by more gentle heating than above only slowed down the rate at which decarboxylation, the primary process, occurred. Attempted photolysis of the adduct (28, RzR'zPh) gave a small amount of tetracyclone and a complex mixture of other products containing the hexaphenyldiazaindene (29).

The intriguing mechanism by which these diazaindenes are formed is, as yet, uncertain. The loss of carbon dioxide from lactones

and eyelid acid anhydrides in the mass spectrometer is well authenticated®** and many examples are known®® where carbon dioxide is expelled from bridged lactones thermally. No examples have been reported, however, where carbon dioxide is expelled thermally, and in the mass spectrometer, from diketones like (28); here the oxygen atoms are, of course, well separated.

^-Methyl and N-phenylphthalimides (36a and 36b) have been

reported®® to lose carbon dioxide under electron impact.

62

NR NR+'/- N R

36a :R=CHa 36b:R=F>h

p-Phthalimidobiphenyl also loses carbon dioxide in this way,®^ although later work®® suggests that the P-CO2 peaks observed for these compounds arise from thermal isomérisation products.It is likely therefore that during thermolysis or on electron impact, the two carbonyl groups in the adducts interact to form a lactone system which can then lose carbon dioxide. This can be represented thus:

■>

(37)

(38)

R

Ph(39)

63

This mechanism would also explain the partial thermal

decomposition of the adducts into tetracyclone, gaseous products,

and acetylene, where the intermediate (37) can either cleave again to give tetracyclone plus thecC-carbonyl-azo intermediate,

or react intramolecularly and lose carbon dioxide from the unstable 8 -membered ring compound (38), the formation of the

aromatic system (39) being the driving force for this step.That pyrolysis of the indazolone adducts (40) gave the

retro-Diels Alder reaction only^? is quite understandable from the above mechanism, since formation of the intermediate lactone would require loss of the benzenoid stability to give the unknown system (41),

(40) (41)

Loss of carbon dioxide from the indazolone adducts did, however,

occur in the mass spectrometer.The diazaindene structure of the thermolysis products (34)

was fully supported by analytical and spectral data. The infra-

64

red spectra of all these compounds were very simple in contrast

to the complicated spectra of the initiàl adducts. It was noticed that the i.r. spectrum of the hexaphenyldiazaindene (29) was almost superimposable on the i.r. spectrum of acetophenoneazine

(M-2 ) which may indicate the presence of this carbon-nitrogen skeleton in the former compound ,

Ph

l-kC

(29)Ph

(42)

yph

All the diazaindenes prepared,exhibited strong blue fluorescence under u.v. light.

Only two examples of the l,7a^diazaindene system have been reported hitherto. Bower and Ramage®^ prepared the parent compound (44, R=H) and the 2-phenyl derivative by oxidative ring-closure of amine (43, R=H and Ph respectively) with potassium ferricyanide.

#3)HO.C

65

Both compounds fluoresced,and were oxidised readily with

potassium permanganate to the corresponding pyrrole-carboxylicacids (45, R=H and Ph).

The ultra-violet spectrum of the hexaphenyldiazaindenewas almost identical in shape with that recorded for the 2 -phenylderivative, and both compounds had almost identical log e A® max.values. The phenyl groups in the former compound, being twisted out of the plane of the diazaindene ring would not be expected to contribute markedly to the conjugation of the system. In the mass spectrum,the first fragment lost from the hexaphenyldiazaindene had m/e 103 (PhCN) which is also the most abundant ion in the mass spectrum of the related 2,3-diphenylindole (46) reported by

Powers.

Ph^ 5 % ------- > ^471 + ^103 (PhCN)

# 2 6 9 ♦ ^ 1 6 6 +J^I03(PhCN)

(46)

66

The breakdown pattern in the mass spectrum of the pentaphenyl-

diazaindene fully supported the proposed structure.Attempts to degrade these compounds by oxidation with

KMnOi+ or chromic acid were unsuccessful, and photolysis of the hexaphenyl derivative in benzene for 7 days gave benzoic acid as

the only pure product. This may have arisen by hydrolysis of benzonitrile, generated photolytically (see above).

Oxidation of 4,5-diphenyl-3-pyrazolidinone.

When a methylene chloride solution of the trans-pyrazolidinone (8 ) was added to a solution of a three fold excess of LTA in methylene chloride, gas was evolved, and trans-stilbene (48, 72%)

was isolated.

A (48)( 8 ) (47)

An attempt to trap the =-carbonyl-azo intermediate (47) with

methanol or with tetracyclone was unsuccessful; trans-stilbene (67% and 77%) was obtained. Also isolated from the reaction with

67

tetracyclone was the H,5-diphenylpyrazolone/tetracyclone adduct

(1%), indicating that a small amount of the unstable intermediate

(47) rearranged to 3,4-diphenyl-2-pyrazolin-5-one (9) which was

further oxidised and trapped.

Rh HLTA/rC ^ (28)

(47)

The oxidation of the pyrazolidinone (8 ) was later reported by

Gillis and Weinkham»0 and the failure to trap the unstable intermediate (47) with dienes (not tetracyclone) was recorded.

Ph

9

SECTION TWO

Amination of pyrazolinones and triazinones

68

Introduction

As discussed in Section I, oxidation of 2-pyrazolin-5-ones with LTA results in the formation of unstable, highly reactive

«-carbonyl-azo intermediates which can be trapped in high yield with dienes. In the absence of a trap mainly polymers are formed. This is without doubt analogous to the oxidation of 3-indazolone,

which has been shown not to give benzocyclopropenone.As 3-amino-l,2,3-benzotriazin-4-one on oxidation gave

benzocyclopropenone,it is reasonable to suspect that oxidation of the analogous 3-amino-5,6-diphenyl-l,2,3-triazin-4-one (1) would, by a similar mechanism, give the stable diphenylcyclopropenone (2).

-NH,. LTA V.^~2Nx .

(2 )

No methods are available however for the preparation of

uncondensed l,2,3-triazin-4-ones,^l and this compound (1) and the parent 5,6-diphenyl-l,2,3-triazin-4-one are unknown.

69

Indeed only one authentic monocyclic 1,2,3-triazine has been

reported. Chandross and Smolinsky found that l-azido-1,2,3- triphenylcyclopropene (3) decomposed in boiling xylene with the formation of 4,5,6-triphenyl-l,2,3-triazine (4, 45%). Photolysis of (4) in benzene for 12 hr. gave diphenÿiacetylene

(72%) and possibly benzonitrile, clearly demonstrating the

instability of this ring system.

3)

hS) -> P h - C = C “Ph 4- PhCN

(4)

The method uséd for the preparation of 3-aminobenzo-

l,2,3-triazin-4-one, i.e. diazotisation of o-aminobenzoyl- hydrazide (5) is not applicable to the diphenyl derivative.

The 3-amino group in 3-amino-2— phenylcinnamic hydrazide exists in the imino form (6 ) and does not participate in the

final ring closure.

70

NHNH- MONO -NH:

Ph1 —

(6 )

Phr*"CONHNH,

-NH

An attempt to synthesise derivatives of this ring system by

amination of suitably substituted 2-pyrazolin-5-ones is described in this section. It was believed that oxidation of l-amino-2- pyrazolin-5-ones (7) could possibly lead to formation of thel,2,3-triazin-4-one system (9) by ring expansion via the nitrene

(8 ) [see 1-aminooxindole, Section III (Introduction)].

%t^H»(7) 1

-NH

71

N-Amination of the triazinone (9) by standard techniques using chloramine or HOS would then give the desired 3-amino derivative

(10).As no examples of amination of triazinones using these reagents

have been reported, an investigation into the stability of some condensed and uncondensed triazinone rings to these conditions has been carried out.

72

Experimental

1. 5,6-Diphenyl-3-oxo-l,2,3,4-tetrahydro-l,2,4-triazine.

3,4-Diphenyl-2-pyrazolin-5-one (2.36 g., 0.01 mole) was dissolved in a solution of sodium carbonate (8.5 g., 0.08 mole) in water (100 ml.) at 70®C, The solution was cooled to 50® and HOS (4.52 g., 0.04 mole) was added over 5 min. The reaction mixture was stirred at 55® for 10 min. and then at 70® for 15 min. when a

pale yellow solid precipitated. This was filtered off, washed with a little hot dilute sodium carbonate solution, then with water and dried. The crude product was triturated with a little ether and crystallised from ethanol to give 5,6-diphenyl-3-oxo-l,2,3,4- tetrahydro-1,2,4-triazine (0.45 g., 16%), m.p. 190 - 191® (Found:C, 71.7; H, 5.2; N, 16.8;*m/e 251. C1 5H13N 3O requires: C, 71.7;H, 5.2; N, 16.7%; MW 251).

Vmax : 3350, 3290, 3240, 3160 (-NH, -OH); 1710 (triazine C=0);1555; 1270; 900; 750, 700, 640 (monosubst. benzene) cm"'.

^max * (log.e 2.33) attributed to stilbene system,m/e: 251, 222, 208, 194, 178, 165, 148, 120, 105, 104, 103, 77.

2. 5,6-Diphenyl-3-oxo-2,3-dihydro-l,2,4-triazine.The diphenyl-tetrahydro-triazinone (0.28 g., 0.011 mole)

suspended in methylene chloride (40 ml.) was added at 20® to LTA (0.75 g., 0,016 mole) in methylene chloride (40 ml.). The mixture

was stirred for 2 hr. at room temperature, then filtered. The

73

filtrate was evaporated to 10 ml., ether (50 ml.) was added, and

the precipitated lead salts filtered off. The ether solution was

evaporated to dryness and the residue washed with a little ether to give 5,6-diphenyl-3-oxo-2,3-dihydro-l,2,4-triazine (0.20 g., 70%) m.p. 220 - 221® (lit.9?, 224 - 225®) (Found: C, 72.2; H, 4.5; N,16.7; m/e 249. CigHiiNgO requires: C, 72.2; H, 4.4; N, 16.9%;

MW 249). The compound was identical in all respects to a synthesised

specimen and a mixed m.p. was undepressed.

3. Synthesis of 5,6-diphenyl-3-oxo-2,3-dihydro-l,2,4-triazine.This compound was made by the method of Biltz.97 Semicarbazide hydrochloride (7 g.) in water (20 ml.) was added

to a solution of benzil (10 g.) in acetic acid (100 ml.). The mixture was refluxed for 3 hr., poured into water (1 1.) and the precipitated solid recrystallised to give pale yellow needles,(10.4 g., 8 8%), m.p. 221 - 222® (lit.9?, 224 - 225®).

4. 4,5-Diphenyl-^-0X0 -imidazoline.

5,6 -Diphenyl-3-0X0- 2 , -dlhydro-1,2,4-triazine (5g.) was dissolved in a solution of sodium carbonate (13 g.) and sodium hydroxide (5 ml., 2N) in water (200 ml.) at 70®. HOS (11 g., 0.1 mole)

was then added over 5 min. during which the mixture frothed and pale

yellow crystals were deposited. The suspension was stirred at 60® for 15 min. then filtered. The solid was washed with hot dilute

sodium carbonate solution, then with water and recrystallised from

74

ethyl cellosolve to give colourless needles (3.2 g., 6 8%), m.p.310 - 311® (dec.) (lit^lO, 320®). The compound had an i.r. spectrum

identical with that of an authentic specimen of 4,5-diphenyl-2-oxo-imidazoline and a mixed m.p. was undepressed.

c5. Synthesis of 4,5-diphenyl-^2-oxo-imidazoline.

Benzoin (3 g.) and urea (1.7 g.) were dissolved in acetic acid (50 ml.) and the solution was refluxed for 2 hr. On cooling, colourless needles precipitated. The product was filtered off and suspended in boiling water (100 ml.) for 2 min. The product was filtered off, washed with hot water and sucked dry. Trituration with ether gave 4,5-diphenyl-2-oxo-imidazoline (3.0 g., 91%) as colourless needles, m.p. 310 - 311® (lit.^^°, 320®).

6 . Amination of 5,6-diphenyl-3-oxo-2,3-dihydro-1.2.4-triazine with(a) With sodium hydride present. '

The triazine (2.49 g., O.OUmole) was added to a suspension of sodium hydride (0.5 g., 50% emulsion) in ether (100 ml.) at

room temperature. The suspension was refluxed for 2 hr., cooled to 20®, and chloramine (0.76 g.) in ether (70 ml.) was added. The

mixture was stirred at room temperature for 24 hr. and stood for 2 days. Sodium chloride was slowly precipitated. The suspension

was filtered and the residue washed with ether. Chromatography of

the filtrate on silica-gel and elution with ether/petrol (1 :1 0 ) gave;

75

(i) l-(4,5-Diphenyltriazol-l-yl)-diethyl ether (0.92 g.,D28%), a colourless oil, 1123 1.6632. An analytical

sample was obtained by distillation at 1 0 0 °/0 . 1 mm.(Found: C, 72.8; H, 6 .6 ; N, 14.1; m/e 293. CigHigNgO

requires: C, 73.7; H, 6.5; N, 14.3%; MW 293).

' max * 3055 (C-H stretch); 1600 (C=C); 1575 (N=N); 1435; 1370; 1330; 1305; 1280; 1260; 1240; 1160 - 1100 (C-O-C stretch); 1060; 1040; 1000; 940; 850; 780 - 690 (monosubst. benzene) cm.PMR: T 8.76 - 9.0 triplet, (3 methyl protons); 8.18 - 8.28 doublet, (3 methyl protons); 6.32 - 6.7 quartet, (2 methyl protons); 4.17 - 4.4 quartet, (1 protor); 2.4 - 2.85 (10 protons).m/e: 293 (P), 264, 221, 193, 165, 105, 104, 103.

Trituration of the oil with cold dilute sodium hydroxide gave 4,5-diphenyl-l,2,3-triazole quantitatively.

(ii) Ether/petrol (1:1) eluted a white solid (1.0 g.). Recrystallisation from boiling nitromethane gave

4,5-diphenyl-l,2,3-triazole, m.p. and mixed m.p. 138 - 139® ( l i t . 138®). An i.r. spectrum was identical with that

of an authentic specimen.

(b) AloneChloramine (4.1 g.) in ether (380 ml.) was added to a solution

76

of the triazine (10 g.) in methylene chloride (1 1 .) and the

reaction was stirred at room temperature for 24 hr. Cyanuric acid (1.7 g., 100%) precipitated during the course of the

reaction and was filtered off. The filtrate was evaporated to dryness and triturated with petrol leaving a white powder (9.7 g.). Crystallisation from boiling nitromethane gave 4,5-diphenyl-1 ,2,3- triazole (75%), m.p. 136 - 137® (lit.108 138©).

77


1. Attempted preparation of 2-chloro-5,6-diphenyl-3-oxo-

1,2,4-triazine.

5,6 -Diphenyl-3-oxo-1,2,4-triazine (2.49 g.) was dissolved in

hot acetic acid (25 ml.) and the solution was cooled to 25®.

Sodium hypochlorite (3.5 ml., 3 molar) was added. A sticky yellow

tar was deposited, which on trituration with ether gave unchanged

starting material ( 2 g.).

2. 5-Benzyl-4-phenyl-3-oxo-l,2,3,4-tetrahydro-l,2 ,4-triazine.

3-Benzy1-4-phenyl-2-pyrazolin-5-one (2.51 g.) was aminated

with HOS (4.52 g.) in sodium carbonate solution according to the

method used in experiment 1. The crude product (1.3 g.), a

complex mixture, was washed with ether. The residue was dissolved in

hot ethanol/acetic acid (1 :1 ), cooled,filtered, and the filtrate

evaporated to dryness. The residue was recrystallised from

aqueous ethanol to give 5-benzyl-4-phenyl-3-oxo-l,2,3,4-tetrahydro-

1,2,4-triazine (0.4 g., 16%), m.p. 134 - 135® (Found: C, 72.7;

H, 5.7; N, 15.3 ; m/e 265. 0%gH^ 5N 3O requires: C, 72.4; H, 5.7;

N, 15.8%; MW 265).

Vmax * 3330' 3270, 3170 (-NH, -OH); 1730 (triazine C*0); 1600 (C*C);

1500; 1475; 940; 780; 770; 710; 700 cm."^.

m/e: 265, 250, 236, 131, 104, 103, 77.

78

6-Benzyl-5-phenyl-3-oxo-2 ,3-dihydro-l,2,4-triazine.5-Benzyl-4-phenyl-3-oxo-l,2,3,4-tetrahydro-l,2,4-triazine

(0.265 g., 1,0 mmole) was oxidised in methylene chloride (10 ml.)

with LTA (0.6 g., 1.3 mmole). Chromatographic work-up on silica-gel, eluting with ether/petrol (1:10) gave 6-benzvl-5-phenvl-3-2,3-dihvdro-

oxc^l.2.4-triazine (25 mg., 11%). Recrystallisation from ether gave straw-coloured needles, m.p. 146° (Found: C, 71.9; H, 5.1;N, 15.7; m/e 263. C16H 13N3O requires: C, 73.3; H, 4.9; N, 15.7%;MW 263).Vmax : 3280, 3200, 3160, 3100 (-NH, -OH); 1660 (C=0); 1575, 1560 (C=C, N=N); 1510; 1495; 1450; 1440; 1370; 1200; 910; 890; 835;730 ,700, 690 (monosubst. benzene) cm.m/e: 263, 234, 219, 206, 186, 122, 104, 103, 91.

3. 5,6-Diphenyl-3-oxo-2,3,4,5-tetr.ahy dro-1,2,4-triazine.

Zinc dust (0.9 g.) was added to a solution of 5,6-diphenyl- 3-0X0— 2,3-dihydro-l,2,4-triazine (1.5 g.) in a mixture of

ethanol (12 ml.) and acetic acid (12 ml.). The mixture was refluxed

for 2 hr., when the reaction appeared to be complete (TLC), and then poured into water. The precipitated solid was recrystallised

from ethanol/acetic acid (3:1) to give colourless needles (1.1 g., 75%), m.p. 258 - 259° (lit.^^, 275 - 276°).

Oxidation of the tetrahydro-triazine with LTA in methylene chloride for 24 hr. gave only a trace of the dihydro-triazinone. Starting

79

material (85%) was recovered,

4. Benzylidene derivative of 5,6-diphenyl-3-oxo-l,2,3,4-

tetrahydro-l, 2 ,4-triazine.A solution of the triazinone (50 mg.) in ethanol (3 ml.)

and benzaldehyde (0.3 ml.) was refluxed for 2 hr. and stood overnight at 20°. The precipitated colourless crystals were filtered off and washed with ether. The benzylidene derivative (40 mg.,60%) had m.p. 203 - 204° (Found: C, 77.8; H, 5.0; N, 12.4; m/e 339. C2 2H17N3O requires: C, 77.9; H, 5.0; N, 12.4%; MW339).

Vmax : 3170, 3070 (-NH, -OH); 1710 (C=0, triazine ring); 1630 (intense, C=N); 1600; 1580; 1260; 1050; 1025; 750; 710; 680 cm.PMR: T 1.52 singlet, (1 proton, benzylidene-CH); 1.18 singlet,(1 proton-NH); 2.2 multiplet, (5 aromatic protons); 2.5 - 2.7

multiplet, ( 10 aromatic protons).

5. Attempted amination of 3,4-diphenyl-2-pyrazolin-5-one with chloramine.Chloramine (0.75 g.) in ether (67 ml.) was added to a

stirred suspension of the pyrazolinone (2.36 g.) and sodium hydride (0.5 g., 50% emulsion) in ether (100 ml.). The mixture was stirred

at 20° for 30 min., then filtered, and the filtrate evaporated to 30 ml. precipitating unreacted pyrazolinone (0.35 g.). Further evaporation gave 4-chloro-3,4-diphenyl-2-pyrazolin-5-one (1.04 g.,

80

40%) identical in all respects to the product obtained by chlorination of 4,5-diphenyl-3-pyrazolidinone (see Section 1,

Experimental).

Discussion

81

By comparison with 3-aminobenzo-l,2,3-triazin-4-one (1)

which on oxidation has been considered^^ to form the highly unstable benzocyclopropenone (2), 3-amino-5,6-diphenyl-l,2,3-

triazin-4-one (3) should give the stable diphenylcyclopropenone (4) under the same conditions.

( I )

N-N-

-NH;

3)

Ph, Ph

Ph4

This comparison would be particularly interesting in view

of the demonstration, in the previous Section, that the corresponding

five-membered ring systems (the pyrazolinone and the indazolinone)

do behave analogously in that neither decomposes to the cyclo-

propenone,

No synthetic route to monocyclic triazinones is known, and

therefore an attempt has been made to prepare 5,6-diphenyl-l,2,3- triazin-4-one from 3,4-diphenyl-2-pyrazolin-5-one by 1^-amination and

82

subsequent oxidative ring expansion. As a consequence of the results obtained, further work on the amination of triazinones was considered desirable.

Amination of 3,4-diphenyl-2-pyrazolin-5-one.

No reactions of 2-pyrazolin-5-ones with chloramine or HOS appear to have been reported up to now. Indeed, there are only very few examples of N-amination of heterocyclic amides generally, Hoegerle^Z has made a series of N-amino-2-pyridones by amination of the sodium salts of methyl substituted 2-pyridones with chloramine in aqueous solution.

CH:

NHz

Wittman**^ similarly aminated the anions of oxindole (5)

and carbostyril (6 ) with HOS to give the respective ^-amino- derivative s.

^ H O S ^

NHi

83

6

HOS

However, when 3,4-diphenyl-2-pyrazolin-5-one (7) was

aminated with HOS in sodium carbonate solution, the only pure product isolated was the six-membered 5,6 -diphenyl-1,2,3,4-

tetrahydro-l,2,4-triazin-3-one (8 , 16%). The structure of (8 ) was established from analytical and spectral data, and by its ready oxidation with LTA to 5,6-diphenyl-l,2,4-triazin-3-one (9),

(7)

HOS

A(8 )

LTA Ph

P h ^ ^ N ' ^ ' X

(9)

These results strongly suggest that the reaction proceeded by

amination of the ambident species (1 0 ) followed by thermal rearrangement of the resulting C-aminopyrazolinone (11) to give the

triazinone (8 ).

84

Ph Ph,

do)

HOS )

1Phv /Ph Ph. ’ ^

(8)A

This reaction scheme is similar to that suggested by

Paquette for the chloramine amination of phenols.90 • Theilacker and Wegner^l had originally postulated the 0-arylhydroxylamine structures (13) for the products from the reaction of the sodium

salts of 2 ,6-di- and 2,4,6-tri-substituted phenols with chloramine.

o “No

/ V o - nh£!» r " _ / \ ■ONH,

(13)

A re-examination of the reaction products by Paquette confirmed

that the products were in fact derivatives of the l,3-dihydro-2H- azepin-2-one system. Thus, when a cold ethereal solution of

85

chloramine was added to a solution of the sodium salts of the

phenols in the phenols at 120-150°, the azepinones (16) were obtained (30-60%). Kornblum and Lurie had clearly demonstrated^^

the ambident nature of the phenoxide ion by carrying out substitution reactions of substituted phenols both in homogeneous and heterogeneous media. When the reactions were carried out in solution only 0 -alkylation of the phenol was observed, while a mixture of 0-alkyl and C-alkyl derivatives were obtained when the reaction was heterogeneous. Thus Paquette's mechanism postulated C-amination of ambident phenoxide ions (14), followed by thermal rearrangement of the 2-aminocyclohexadienones (15) to give the

observed l,3-dihydro-2H-azepin-2-ones (16).

RR

(15)QH M

: R

16

In a later paperPaquette and Farley determined the course of this reaction when the group R was varied. Where R and R' were

methyl groups, C-amination in each ortho-position was equally

86

favoured. When R was increased in size however,steric factors

influenced the course of the reaction, and the product ratio was

directly related to the steric hindrance at each site.Applying these considerations to the pyrazolinone (7),

amination at Ci+ which is occupied by a bulky phenyl group appears

to be less likely than 0 -amination, a reaction which has been s h o w n t o occur when potassium phenoxide itself is treated with HOS.

(17)

%

0-Phenylhydroxylamine (17) is a reasonably stable liquid and

the structure appears to be well authenticated. No ring enlargement reactions of this compound have, however, been reported.

Initial 0 -amination of the diphenylpyrazolinone anion (18)

followed by rapid rearrangement would formally give the C^-amino derivative (19) which rapidly undergoes rearrangement to the triazinone as before.

(19)

87

The 5,6-diaryl-tetrahydrotriazin-3-one system is unknown; the product obtained by pyrolysis of the semicarbazide of mesityl oxide has been tentatively suggested to have the tetrahydro-1,2,4-

triazin-3-one structure (20).

I-H N-HChUCK

(20)Mixich^G has recently reported the preparation of a novel 7~methylbenzo derivative of this ring system. Treatment of the tetrahydrotriazinone (8 ) with benzaldehyde in refluxing ethanol gave a crystalline benzylidene derivative. A similar anomolous reaction has been reported by Godtfedson and Vangedal®® who prepared a crystalline benzylidene derivative of 5-phenyl-3-

pyrazolidinone (22) and assigned to it the betaine structure (23).

(22)

PhPhCHO ) y

PhCfH

(23)

88

I r PhCHO ^ ^ ^ ^

A

(8 )

P h J l ^ ° ' p h i s ^HCPh A

orP h y ^ ^ -

^ V L

Differentiation between these three possible structures for the

benzylidene derivative of (8 ) from spectral data could not be achieved. A further possible structure could arise by the triazinone (8 ) being in equilibrium with a small amount of

l-amino-4,5-diphenylimidazolin-3-one which can then form a normal benzylidene derivative.

Ph

PhNH:

PhPhCHOPh

N=CHPh

Oxidation of 5,6 -diphenyl-l,2,3,4-tetrahydro-l,2,4-triazine-3-one (8 ) with LTA gave 5,6 -diphenyl-l,2,4-triazin-3-one (9, 70%),

whose structure was confirmed by synthesis from benzil and semi

carbazide hydrochloride by the method of Biltz.^?

89

PhPh PhPhPh

8 )

c=oc=oIPh

NHz+ 9 = 0

NHISIH,

Reduction of the diphenyltriazinone (9) with zinc and acetic

acid gave a tetrahydro derivative (2 1 ) isomeric with thetetrahydro derivative obtained from amination of the pyrazolinone (7)

PhAcOH Ph

(21)(9)The spectral and chemical properties of these two derivatives were markedly different. Oxidation of (21) with LTA was extremely slow, and showed the formation of (9) to only a slight extent after 48 hr.

When 3,4-diphenyl-2-pyrazolin-5-one (7) was aminated with

chloramine in ether with sodium hydride present, the product was the 4-chloropyrazolinone (24) identical to that prepared by chlorination of 4,5-diphenyl-3~pyrazolidinone (see Section 1).

Chloramine is therefore acting as a chlorinating agent in this reaction.

90

Ç k K ,

A

(24)

The amination product of 3-benzyl-4-phenyl-2-pyrazolin-5-one was less easy to purify than in the 3,4-diphenylpyrazolinone case.

The tetrahydrotriazinone (25) when oxidised with LTA gave the previously unknown 5-phenyl-6-benzyl-l,2,4-triazin-3-one (26,

11%).

LTA YH

(25)

P h C U j f ^ N Y ' »

(26)

Amination of 5,6-Diphenyl-l,2,4-triazin-3-one.

This interesting pyrazolinone to triazinone ring expansion

by HOS amination led us to study the stability of the 1,2,4- triazin-3-one ring system itself to amination. 5,6 -Diphenyl-1,2,4-triazin-3-one was dissolved in a mixture of sodium carbonate

and sodium hydroxide in water at 70°. These conditions were necessary for the complete solution of the triazinone. When HOS was added slowly, vigorous frothing occurred, and pale yellow

91

crystals were immediately precipitated. Recrystallisation from ethyl (sellosolve gave 4,5-diphenylimidazolin-2-one (27, 6 8%).

An alternative synthesis from benzoin and urea confirmed the structure of the product.

Ph

Ph

9

HOSH Ph

H Ph(27)

The conversion of 5,6-diphenyl-l,2,4-triazin-3-one to 4,5-diphenylimidazolin-2 -one under reducing conditions has been described by Biltz.97 The reduction occurred in two stages; the first was the conversion of the diphenyltriazinone (9) into the tetrahydrotriazinone (21) with zinc and acetic acid. Treatment of this compound with phosphorus and hydriodic acid gave the diphenylimidazolone (27, 75%) and ammonia.

' ” ' 1^ Y " T rP h '% jY ''H P h '% jY ‘'H

(9 ) (21) (27)

PhP/hi

PhNH,

92

The relatively mild conditions used in the amination suggest

that a different mechanism is involved. Tentative schemes are outlined below.

(i) With initial N-amination:

Ph

Ph

PhPh

(31)

-N:

PhPh

(27)

(28)

NH.OSO. ) Y ^

(29)

Ph

IPhPh

(30)

(ii) With C-amination:

93

Ph Ph

Ph

(9)

Ph

i--N»

hi

Ph A (27)

NKOSO;

Ph

Ph

Ph

In scheme (i), N-amination in the 2-position followed by

rearrangement to the fused diaziridine (30), could lead to formation

of a seven-membered «-carbonyl-azo compound (31) by ring-opening.

Preferential loss of nitrogen from this species would then give the imidazolone (27).

A less likely route is given in scheme (ii) where C-amination

followed by rearrangement would again give the seven-membered «-carbonyl-azo compound (31) which could decompose as before.

94

Attempted N-amination of 5,6-diphenyl-l,2,4-triazin-3-one with

chloramine in ether in the presence of sodium hydride, gave two

products after chromatography. The first was a pale yellow oil

which, from analytical and spectral data, and its rapid quantitative conversion to 4,5-diphenyl-l,2,3-triazole with dilute sodium hydroxide, was characterised as l-(4,5-diphenyltriazol-l-yl)- diethyl ether (32). The second product was an impure white solid, which, after crystallisation from nitromethane was identified as4,5-diphenyl-l,2,3-triazole (33).

CHjCHOCHiCHj A

( 9 ) (32) (33)

The PMR spectrum of the ether (32) confirmed the proposed structure.

The 2-methyl and 2*-methyl groups showed up as a doublet (t 8.18 - 8.28) and a triplet (% 8.76-9.0) respectively. The methylene group was a quartet (t 6.32-6.7) while the methine proton in the

1-position was a quartet (t 4.14-4.4). The aromatic protons of

the two phenyl groups appeared as a broad multiplet (t 2.4-2.85). Benzotriazole (34) cannot be aminated with chloramine, but in ether

95

gives solely the 1-ether (35). 18

N q h AmKCIEther

(34)

r v A,/

C H 3C H O C H 1C H 3

(35)

Comparison of the PMR spectra of the diphenyl and benzo-derivatives showed a striking similarity. Conversion of the ether (35) to benzotriazole with dilute sodium hydroxide is also quantitative.The formation of (35) has been s h o w n t o proceed through the intermediate 1-chlorobenzotriazole (36) which, by a radical mechanism adds to diethyl ether.

H

NH^CI ^ Ether

A A s j /

(36)

(35)

It thus appears that the ether (32) may also be formed from

l-chloro-4,5-diphenyl-l,2,3-triazole. No evidence for the formation

of this chloro- compound has been found in the chloramine amination of 4,5-diphenyl-l,2,3-triazole, therefore it appears to be a

96

transitory intermediate formed during ring contraction of the

triazinone under these conditions. The presence of sodium hydride in the reaction of 5,6-diphenyl-1,2,4-triazin-3-one with chloramine

was found to be unnecessary. Treatment of a solution of the diphenyltriazinone (9) in methylene chloride with an excess of

ethereal chloramine gave, after stirring for 24 hr., 4,5-diphenyl-1,2,3-triazole (33, 75%). Cyanuric acid (100%) precipitated during the course of the reaction and none of the ether (32) could be detected (TLC).

This interesting ring contraction gives a ready synthesis of 4,5-diphenyl-l,2,3-triazole, a compound which is usually prepared by nitrous acid deamination of the 1-amino derivative, itself prepared by oxidation of benzil bis-hydrazone with selenium dioxide.

PhC=N-NHi MONO V

PhC=N NHi P h '^ N P h " ^Ph NH» A

97

Carbon has observed a similar ring contraction in the

benzotriazine series.Treatment of 3-amino-1,2,4-benzotriazine-1-oxide (37) or the 2-oxide (38) with hot aqueous sodium hydroxide

gave benzotriazole and its 1-carboxamide. Pyrolysis of the carboxamide at 160° gave benzotriazole and cyanuric acid.

(37) CONH,(38)

The presence of the^-oxide function on one or other of the two adjacent nitrogen atoms in the triazine ring was necessary for the ring contraction. His mechanism proposed initial attack of hydroxyl ion at the 3-position of the triazine ring to form the species (39) which can be converted to (40) by proton migration. Ring opening, with the formation of the azoxy compound (41), and rearrangement to the diazonium hydroxide followed by ring contraction, would give the benzotriazole 1-carboxamide

98

?

CONH*

Loh

(39)

OH'

% ^ N = C^NH*

?"

(40)

O'I

(41)

/)-■^NH*

Hydrolysis of the 1 -carboxamide would then give the observed benzotriazole.

The substitution of the triazine ring in species (39) above

would be identical to that which would result from attack by chloramine on the diphenyltrazinone (9) followed by rearrangement

of the amino group to the adjacent carbonyl carbon atom, except for the presence of the N-oxide function in (39). Rearrangement

to the diphenyl-l-carboxamide, then followed by hydrolysis of this unstable compound^^ as it is formed, would give the observed

diphenyltriazole and cyanuric acid.

99

(9)

p J L /A

+ HNCO

Base

P h " ^ s ^ "

Ph'v.-HM

P h - ^ >CONH*

/-|\ P h - ^ i ^ ^ N H

S>P h ^ N - C :' NH, p h A y = N

The absence of any transient colour during the reaction may preclude the diazo intermediate above (cf.ref, 99), although

the slowness of the reaction may mean that no appreciable intensity

of colouration occurs. In this case the probable reaction course is via a seven membered ring such as (42) described above, which collapses to diphenyltriazole rather than rearranges and loses nitrogen to form the diphenylimidazolone; the polaBity of the

solvent used may be the deciding factor.

+ HNCO

It is interesting to note that benzo-1,2,3-triazin-4-one (43)

can be aminated in the 3-position with HOS in sodium carbonate

solution and no ring contraction occurs.

100

-NH*

From the results of these aminations of the five-membered2-pyrazolin-5-one and six membered 1,2,4-triazin-3-one system it appears that the extreme lability of the monocyclic systemson amination is mainly due to their unfused nature. Free electron

transfer through the heterocyclic ring can occur without the

involvement of the n-electron system of a fused ring, which will always tend to remain aromatic.

These observations also suggest that the synthesis of3-amino-5,6 -diphenyl-1,2,3-triazin-4-one (3) by amination of

5,6-diphenyl-l,2,3-triazin-4-one runs the risk of similar ring contractions occurring, with the possible formation of 3,4-diphenyl- 2-pyrazolin-5-one (45) after loss of nitrogen from the seven membered «-carbonyl-azo species (44).

101

Base ^Ph

" A "(44)H H

Phv/"-N(

P h ^ V ^A

yH

-N:

Ph.

P h ^ % : ^

■+ "'J\ Î^-NH^

(3)

/H

Ph

P h ' ^ ^H

-H

(45)

SECTION THREE

Oxidation of N^aminopyridones

102

Introduction

Amino-nitrenes

During recent years much interest has been focused on

the chemistry of nitrenes; these are highly reactive, uncharged, univalent electron-deficient nitrogen species containing six electrons in the nitrogen outer valence shell. Several reviews2^*25)2G of general nitrene chemistry have appeared in the literature.This introduction will deal solely with amino or N-nitrenes,R2N-N:.

N-Nitrene intermediates have been postulated in many reactions.The idea that oxidation of unsymmetrically substituted benzylaryl-

hydrazines with mercuric oxide proceeds through an N-nitrene intermediate (2) was first put forward by Busch and Lang^? in 1936.When a series of substituted ^-benzyl-^-phenylhydrazines (1) were oxidised in this way the tetrazenes (3) and/or the aldehyde phenylhydrazones (4) were formed in varying proportions depending

on the conditions used.

ArCHg ArCH% Ar-NH-N=CHArN-Nl

(1)

\ HgO ..J)N-NH2 -------> 'N-N: > (4)

Ar +(2)

ArCH2v ^CH2Ar\-N«N-N

A r ^ Ar

(3)

105

Earlier workers^® had observed that oxidation of 1,1-

dibenzylhydrazine (5) with mercuric oxide in ethanol gave dibenzyl (6 ) as the only organic product, nitrogen being evolved quantitatively. When chloroform was used as the solvent instead of ethanol a good yield of tetrabenzyltetrazene (7) was obtained

with no evidence of dibenzyl formation.

PhCHN-NHo HgO^Ethanol

PhCH,

PhCH^CH^Ph +

(6)

PhCH^ ^ CH^PhN-N=N-N/ XPhCHg ^ CH^Ph

(7)

Repetition of this work by Wieland^S gave only small amounts

of tetrazene, the major product being dibenzyl. Evidence that

this is an intramolecular reaction was provided by Hinman and Hamm|® the oxidation of mono-£-substituted 1 ,1 -dibenzylhydrazines (8 ) with mercuric oxide in 95% ethanol gave only 'mixed' dibenzyls (9) and no symmetrically substituted products.

ArCK

PhdHx(8 ) OQ)

ArCH»CHiPh + Nx

(9)

104

When one of the benzyl groups was replaced by furfuryl the product was the expected 2-(g-phenylethyl)-furan. Evidence for the formation of N-nitrene intermediates such as (10) in

the oxidation of 1 ,1 -dialkyIhydrazines is supported by the

work of McBride and K r u s e w h o obtained spectrophotometric

and chemical evidence for the formation of the N-nitrene (13), stabilised as its conjugate acid (1 2 ), by oxidation of 1 ,1 - dialky Ihydrazines (11) in acid solution.

[0] + +^ N-NH2 -------^ ^ N = N H « — > R 2N-NH

R t / H^O

(11) (12)

When the acid solution was neutralised, tetra-alkyltetrazenes (14) were formed in high yield.

+ oh" "R2N-NH > R2N=N > R2N-N: > R 2N-N=N-NR2

(13) (14)

Overberger and workershave attempted to rationalise the widely differing results obtained by early workers from oxidations

of 1,1-disubstituted hydrazines under different conditions. They

105

proposed the terms "normal" to describe tetrazene formation, and "abnormal" to describe fragmentation of the molecule with

loss of nitrogen and subsequent carbon-carbon bond formation.

When he oxidised 1,1-dibenzylhydrazine with bromine in ethanol

both reactions were observed. Dibenzyl (9%) was formed by the "abnormal" mechanisms, the remainder of the product, tetrazene acid-decomposition products, being formed by the "normal" mechanism. Oxidation of the hydrazine with tert.-butylhypo- chlorite gave tetrazene (15,5%), dibenzyl (12%) and dibenzyl- amine (13%).

PhCHo

PhCH^(5)

:n-nh2Br2 PhCH2

■> ^^^N-NHX <- PhCH2

-HX

t-BuOCl PhQH2

PhCH2(5)

N-NH2

PhCH2^ N - N :

PhCH2(15)

PhCH2CH2Ph + N2 +

PhCH2-N=N-N=N^CH2Ph + (PhCH2)2NH

This is indicative of the common nitrene intermediate (15)

being formed in each reaction, leading to common products. By replacing the two benzyl groups in 1 ,1 -dibenzylhydrazine with

106

a saturated ring Overberger has demonstrated the generality of this fragmentation reaction to systems where, as in the 1 ,1 -

dibenzylhydrazine case, a resonance stabilised ionic or radical intermediate is formed. Thus oxidation of l-amino-2,6-dicyano-2 ,6 -dimethylpiperidine (16) with bromine in ethanol gave a mixture

of cis and trans-1,Z-dicyanocyclopentanes (17) together with the ring opened olefin (18).

NH

H 3 0

CHi (1 7 ) CHa(16)

CN (18) CN

When the cyano groups were removed the oxidation proceeded as with 1 ,1 -dialkylhydrazines, i.e. with tetrazene formation.

HaO

NHi

n - n = n - n

CHa CH>

107

This resonance stabilisation of the intermediate, as nitrogen

is lost, has been suggested^^ as part of the driving force required for nitrogen elimination in preference to tetrazene formation. The oxidation of cis and trans-l-amino-2,6 -diphenyl-

piperidine was found to follow a similar pattern, the radical or ionic intermediate being stabilised by delocalisation over two phenyl rings. Oxidation of the cis-isomer (19) with mercuric oxide gave cis-1,2-diphenylcyclopentane (20, 65%) and 1,5-diphenyl-

1-pentene (21, 25%); whilst oxidation of the trans- isomer (22) gave trans-1,2-diphenylcyclopentane (23, 59%) and cis-1,2-diphenylcyclopentane (20) together with the olefin (21, 14%). Isomérisation

of the trans-l-amino-2 ,6 -diphenylpiperidine to the more stable cis- isomer during oxidation was suggested as the reason for the

non-stereospecificity of the latter reaction.

NHi(19)

■ ^ 0 - > + Ph-CH=CH(CHjj-Ph

(21)

'HNHi(22)

HgO ) P

V Ph(20) (23)

+ (21)

108.

Two mechanisms have been suggested for these rearrangements,

both of which involve the formation of the N-nitrene (24).

One possibility was that the ring expansion of the nitrene to give the seven-membered cyclic azo-compound (25) would be followed by loss of nitrogen to give the products.

P h ^N Ph Ph W Ph

(24)

( (2 0 ) + (2 1 )

+ (23) (25)

An isomer of (25) was synthesised and found to be too long lived at the reaction temperature to be considered as an intermediate. Its decomposition was also completely non-stereospecific. The second mechanism involves a concerted loss of nitrogen from the nitrene with ring contraction.

An attempt to reduce l-nitroso-2 ,6-diphenylpiperidine (26)

with sodium dithionite was observed by Overberger^** not to give

the expected 1 -amino derivative but to cause fragmentation of the

109

molecule with loss of nitrogen to give 1 ,2-diphenylcyclopentane

stereospecifically. These observations have prompted the

proposal of the involvement of a three-centre type mechanism

to explain the stereospecificity of these reactions.

HH -Ph

p/Sn(26) %

A'Ph

NH-

This view ** was strengthened by the isolation of 1,2-diphenyl- cyclobutanes (28) from the oxidation of l-amino-2,5-diphenyl- pyrrolidine (27), The buta-l,4-diyl radical (30) which would be the intermediate formed by decomposition of the cyclic azo-

compound (29) is known to fragment to styrene (31).

Ph-< KPh N=N'(29)

Ph"

— NzPh

Ph Ph (28)

\_pf;-- > Ph-CH=CH,

(30) (31)

n o

An alternative method for the generation of N-nitrenes has been reported by Carpino^^ involving decomposition of

benzenesulphonyl and tosyl derivatives of 1 ,1 -disubstituted

hydrazines with base. l-Toluene-2 ^sulphonamido-2 ,7 -dihydro-3,4,5,6-dibenzazepine (32) decomposed rapidly and gave 9,10-

dihydrophenanthrene (34) in high yield via a postulated N- nitrene intermediate (33),

2-3min.

(34)(32) (33)

Similarly l,l-dibenzyl-2-benzenesulphonhydrazide (35) gave

dibenzyl in complete analogy to the oxidation of the If-amino derivative,

oh"(PhCH2)2.N-NH,S02Ph --------> PhCH2CH2Ph

(35)

This method was also used by Baker, McOmie and Preston^? to prepare benzocyclobutene (37) by decomposition of 1,3-dihydro-2-toluene-p-sulphonamidoisoindole (36) in pyridine.

Ill

N-NHSOJbs Pyridine

(37)

Decomposition of the nitrene (38) was envisaged to proceed through the stabilised diradical (39) which subsequently ring- closed to give the product. This was confirmed by Carpino^^ who obtained the dimeric compound (41) by mercuric oxide oxidation of the N-amino derivative (40).

N-NH, - 1 5 2

CHi(41)

N-N:

(43) (42)

112

0-Xylylene (43) generated by pyrolysis of 0-methylbenzyl-trimethylammonium hydroxide (42) is known^ to dimerise to the

spiro-dimer and also to give benzocyclobutene.

Application of decomposition of ^-tosylamido compounds to the triazole system has provided a new approach to the synthesis of alkynes. Photolysis of a number of lithium salts

of toluene-£-sulphonamido~l,2,3-triazoles has been carried out by Wiley.39 The lithium salt of l-£-toluene-sulphonamido-4,5- diphenyltriazole (44) is reported to lose nitrogen and give tolan (45) in 85% yield, analogous to the oxidation of the1-aminotriazole (46) which gives tolan quantitatively.

(44)+ n;Li SOJbs

N/

LTA

P h— C =C-"Ph (45)

r >

tllHv

#6)

115

Photolysis of the sodium or lithium salt of 1-g-toluene-

sulphonamidobenzotriazole (47) has recently been shown to give benzyne (48) which can be trapped with furan to give the naphthalene endoxide (49) or with tetracyclone to give tetra-

phenylnaphthalene (50).^0

CO hs

NU + \ o j b s (47)

N f LTA

Q 03(49)

This is analogous to the LTA oxidation of 1-aminobenzotriazole (51) which gives benzyne in high yield^^ thus strongly indicating

the initial formation of the N-nitrene (52) in both reactions.Examples of intramolecular reaction of Nnitrenes with

retention of nitrogen are extremely rare, dimérisation to stable

tetrazenes, or fragmentation of the molecule being the preferred

reaction course. The N-nitrene of pyrrolidine (54) has been shown by Lemal^^ to undergo all three reactions depending on the

reaction conditions used. Generation of the nitrene by

thermolysis of sodium N-benzenesulphonamidopyrrolidine (53)

in diglyme at 175® resulted in concerted fragmentation of the

molecule to give nitrogen and ethylene.

A

A-Nd^ 'SO.Ph

-> 2CHpCH» + Ni

(53) (54)Oxidation of 1-aminopyrrolidine (55) with mercuric oxide

in ether however gave the bis-tetramethylenetetrazene (56).

114

HqO

%(56)

No explanation of these apparently anomalous results could be offered although in a later paper** the use of aprotic

solvents was found to favour tetrazene formation. When the N-tosylamido derivative (53) was decomposed in water, gas

evolution was suppressed, and 2,3,4,5-tetrahydropyridazine (57) was formed (56%) by intramolecular ring expansion of the nitrene.****

115

AH » 0

. N- Na+ ^Oa.Ph(53)

%N:'(57)

The same reaction also occurred when pyrrolidine itself was treated with nitrohydroxylamine (introduced as Angeli's salt Na2 0N.N0 2 ) ^ 3 in acid solution.

The oxidation of 1-amino-oxindole (58) with LTA was observed by Baumgarten**^ to give 3-cinnolinol (59) in 78% yield.

The suggested mechanism postulates the generation of the nitrene (60) which is stabilised and can rearrange to the cinnolinol.

(59)

116

Wittman^G later suggested a modified mechanism in which

the nitrene rearranges in a manner similar to the l,l'-aryl-

benzylhydrazine-phenylhydrazone rearrangements described

above.

Mechanism A was considered the more likely by comparison with the mechanism of Hoffman rearrangements. When 1-aminocarbosty ril

(61) was oxidised in a similar way deamination occurred with no ring expansion or fragmentation.

LTA

3-Amino-benzoxazolin-2-one (62) was oxidised by Atkinson

and Rees**® with a view to generating benzyne by fragmentation of the nitrene (63).

117

NHi(62)

+ Na, + CO,

Neither this fragmentation nor the ring expansion occurred however, and tetrazene formation was the predominant reaction.

The N-nitrene (63) derived from 3-amino benzoxazolin-2-one was trapped by dienes to give aziridines in good yields stereospecifically; when conjugated dienes were used 1 ,2 - rather than

1,4-addition of the nitrene was observed.^®

R R I N.

A A A

118

This suggested that the nitrene was generated and trapped in the singlet state which could be highly stabilised by the delocalisation shown.

In this section the generation and reactions of the I^-nitrene derived from l-amino-3,4,5,6 -tetraphenyl-2 -pyridone will be described, and substantial evidence for its existence will be presented. Work done on similar pyridone-type systems will also be described.

119

Experimental

1. Preparation of l-amino-3,4,5,6-tetraphenyl-2-pyridone.

(a) From 3,4,5,6-tetraphenyl-2-pyrone.

3,4,5,6-Tetraphenyl-2-pyrone was prepared by the method of

Putter and Dilthey.^^^A mixture of acetic acid (40 ml.), acetic anhydride (30 ml.)

and hydrogen peroxide (20 ml., 1 0 0 volume) was heated on a steam bath until it began to reflux, and was then added, with rapid stirring, to finely ground tetracyclone (10 g.). The suspension was refluxed for 20-30 min. until the tetracyclone had dissolved to give a pale yellow solution. This was cooled in ice, and

poured into water (1 1 .) precipitating a pale yellow solid. Crystallisation from ethanol gave the pyrone (10.0 g., 64%) as pale yellow crystals, m.p. 164° (lit.^^^, 164-165°).

A solution of the pyrone (5 g.) and hydrazine hydrate (10 ml., 99% solution) in ethanol (100 ml.) was refluxed for 18 hr., cooled, and poured into water (400 ml.). Addition of conc. HCl (20 ml.) precipitated the crude product. Chromatography

on neutral alumina, eluting with ether/petrol mixtures, gave:(i) Colourless crystals (0.30 g.), m.p. 250-252° (rapid

heating) (Found: C, 83.0; H, 5.4; N, 6 .8 ; m/e 414.

C2 9H2 2N2O requires: C, 81.6; H, 5.3; N, 6 .8%; MW 414).

120

Vmax : 3200; 3100; 1665; 1600; 1500; 1160; 1035; 775; 735; 705 cm."^. PMR: T 0.79 broad singlet, (1 proton, NH); 4.72 broad singlet,(1 proton); 2.5-3.05 multiplet, (20 aromatic proton), m/e: 414 (P), 296,267,229, 178, 165, 148, 146, 140, 84, 77.

When exposed to daylight the crystals slowly turned pink, tetra

cyclone being formed on the surface of the crystals. Oxidation of this compound (80 mg.) with LTA in methylene chloride caused

gas evolution. Tetracyclone (8 mg.) was formed, together with a yellow compound, m.p. 75-85° (dec.) (v^~^ : 1690, 1770 cm. ^),which on

gently heating above the melting point gave some tetracyclone (TLC),

(ii) l-Amino-3,4,5,6-tetraphenyl-2-pyridone (1.8 g., 35%). Crystallisation from benzene/petrol (1:1) gave colourless needles, m.p. 187-188° (Found: C, 81.7; H, 5.3; N, 6.7; m/e 414. C2 9H2 2N2Orequires: C, 81.6; H, 5.3; N, 6 .8%; MW 414).

Vmax * 3050 (-NH2 ); 1625 (pyridone C=0); 1595; 1580; 1550;750; 740; 700 cm."^.

Amax : 337 (log e 4.03), 218 nm (4.34).PMR: T 4.46 broad singlet, (2 protons, -NH2 ); 2.77-3.16 multiplet,

(20 aromatic protons), m/e: 414, 397, 296, 192, 178.

(b) From 3,4,5,6-tetraphenyl-2-pyridone.

3,4,5,6-Tetraphenyl-2-pyridone was prepared by the method of

121

Waj on and Arens. *-Benzoylbenzyl cyanide (33 g.), acetic acid (45 ml.) and

conc. sulphuric acid (13.5 ml.) were refluxed together until the evolution of carbon dioxide had ceased (1-1.5 hr.). The resulting

brown mixture was cooled, poured into ice-cold water, and the suspension obtained was neutralised with sodium carbonate solution.

The solid was filtered off and triturated with acetone. Crystallisation from acetic acid gave 3,4,5,6-tetraphenyl-2- pyridone (11 g ., 38%), m.p. 250-270°. A second recrystallisation from methylene chloride/benzene (1 :1 ) gave colourless needles, m.p. 270-272° (lit.^^^, 272-273° uncorrected).

Sodium hydride (0.26 g., 50% emulsion) was added to a

solution of the pyridone (2 . 0 g.) in methylene chloride ( 1 0 0 ml.). The mixture was refluxed for 3 hr., cooled to 20° and chloramine (0.4 g.) in ether (36 ml.) was added. After stirring for 48 hr. at 20-25° the mixture was filtered and the residue washed with

ether. Evaporation of the filtrate to dryness gave a fawn solid. Crystallisation from benzene/petrol gave the N-aminopyridone

(1.05 g., 50%) as colourless needles, m.p. and mixed m.p. 187-188°. Spectral properties were identical with those of the product

prepared by method 1 (a).The benzylidene derivative was prepared by refluxing the

N-aminopyridone (120 mg.) with benzaldehyde (0.4 ml.) in ethanol

122

(6 ml.) with a trace of acetic acid, for 3 hr. Crystallisation of the product from ethanol gave yellow needles (98 mg., 65%),

m.p. 204-205° (Found: C, 86.0; H, 5.3; N, 5.6. C3 6H26N2O requiresC, 86.1; H, 5.2; N, 5.6%).

^max * (pyridone C=0); 1600 (C=N); 1595 (aromatic C=C); 1520;1490; 1450; 1080; 1030; 750; 720; 700 cm"!

^max * (log E 4.47), 353 nm (3.89).

2. Deamination of l-amino-3,4,5,6-tetraphenyl-2-pyridone.

Sodium nitrite (17 mg.) in water (0.2 ml.) was added to a solution of the N-aminopyridone (100 mg.) in acetic acid (3 ml.) and water (0.5 ml.) at 0°. After 1 hr. the precipitated solid was filtered off and recrystallised form methylene chloride/petrol (1:3) to give 3,4,5,6-tetraphenyl-2-pyridone (91 mg., 95%), m.p. and mixed m.p. 271-272°. ,

123

3. Oxidation of l-amino-3,4,5,6-tetraphenyl-2-pyrid6ne.

(a) Alone.LTA (0.2 g., 0.45 mmole) was added over 2 min. to a stirred

solution of l-amino-3,4,5,6-tetraphenyl-2-pyridone (100 mg., 0.24

mmole) in methylene chloride (25 ml.) at 20°. Gas was evolved

and the mixture became pink. Tetracyclone could be detected (TLC) at the beginning of the oxidation but it slowly disappeared. After stirring for 1 hr., when no starting material could be detected (TLC), glycerol (1 drop) was added. The reaction mixture was adsorbed onto neutral alumina and chromatographed. Elution with ether/petrol (1:1) gave 3,4,5,6-tetraphenyl pyridazine (54 mg., 59%). Recrystallisation from ether/petrol (1:2) gave pale yellow needles, m.p. and mixed m.p. 195 - 196° (litJ^^, 196 - 197°) (Found:

C, 87.3; H, 5.2; N, 7.3; m/e 384. Calc, for C2 8 H2 0 N2 • C, 87.5;H, 5.2; N, 7.3%; MW 384). An i.r. spectrum was identical to that of a specimen prepared by the method of Carboni and Lindsay.

Elution with ether gave 3,4,5,6-tetraphenyl-2-pyridone (18 mg., 15%), m.p. and mixed m.p. 270 - 272° (l i t ^ 272 - 273°).

(b) In dimethylsulphoxide.

LTA (1.1 g., 2.4 mmole) was added over 2 min. to a stirred

solution of the I^-aminopyridone (0.9 g., 2.2 mmole) in dry dimethyl

sulphoxide (30 ml.). After 1 hr. the reaction mixture was poured

124

into water ( 2 0 0 ml.) and the brown precipitate was filtered off,

washed with warm water and dried. The solid was ground to a fine powder and extracted with boiling chloroform (100 ml.). The chloroform solution was evaporated to 10 ml. and petrol was added

until the solution was slightly cloudy. Storage at 0° for 12 hr. gave N-(3,4,5,6-tetraphenylpyrid-2-on-l-yl)-dimethylsulphoximine (0.9 g., 84%). Crystallisation from methylene chloride/petrol (1:5) gave colourless needles, m.p. 247 - 248° dec. (Found: C, 75.7;H, 5.3; N, 5.6; S, 6.2; m/e 496. C3 1H26N2SO2 requires: C, 75.9;H, 5.3; N, 5.7; S, 6.5%; MW 496).

v^ax : 1630 (amide C=0); 1580; 1560; 1215; 1175; 1040 - 1025 (doublet, $=0)11% 860; 750; 700 cm.” .

^max ’ (log E 3.98); 223 nm (log e 4.57).PMR: T 6 .‘93 singlet, (6 methyl protons); 2.82 - 3.18 multiplet,

( 2 0 aromatic protons).m/e: 496 (P), 425, 412 (P-DMSO), 398, 382, 356, 278, 265, 178.

(c) In the presence of cyclohexene.l-Amino-3,4,5,6-tetraphenyl-2-pyridone (1.0 g., 24 mmole)

was dissolved in methylene chloride (5 ml.) and cyclohexene (25 ml.) was then added. LTA (1.5 g., 3 mmole) was added over 2 min., and after 1 hr

the mixture was adsorbed directly onto neutral alumina and chromatographed. Ether/petrol mixtures eluted:

125

(i) Tetracyclone (1 mg,), m.p. and mixed m.p. 216 - 218° (lit.'^\ 2 2 0°).

(ii) 3,4,5,6— Tetraphenylpyridazine (193 mg., 28%), m.p. and mixed m.p. 195 - 196° (lit.^S, 196 - 197°).

(iii) 2-(3,4,5,6-tetraphenylpyrid-2-on-l-yl)-7-azabicyclo-[4,l,0]-heptane (0.3 g., 25%). Recrystallisation from ethanol

gave colourless needles, m.p. 219 - 221° (Found: C, 85.1; H, 6.2;N, 5.6; m/e 494. C3 5H30N2O requires: C, 85.0; H, 6.1; N, 5.6%;MW 494).

v^ax • 1630 (amide C=0); 1600; 1580; 1570; 1495; 1230; 1180; 1165; 1080; 1030; 780; 760; 700 cm.’ .

Xmax : 227 (log e 4.33), 342 (4.07).PMR: T 7.34 singlet, (2 protons, aziridine ring); 8.75 multiplet,(8 methylene protons); 3.0 multiplet, (20 aromatic protons), m/e: 494, 399, 398, 178, 77.

(iv) 3,4,5,6-Tetraphenyl-2-pyridone (145 mg., 7%), m.p. and

mixed m.p. 270 - 272°.

(d) In the presence of diphenylsulphoxide.The N-aminopyridone (0.5 g., 13 mmole) and diphenylsulphoxide

(1.0 g., 5 mmole) were dissolved in methylene chloride (20 ml.).

LTA (0.65 g., 1*4 mmole) was added portionwise over 2 min. After

1 hr. the reaction was complete (TLC). The reaction mixture was

adsorbed onto silica gel and chromatographed. Ether/petrol mixtures

126

eluted;

(i) 3,4,5,6— Tetraphenylpyridazine (125 mg.j 34%), m.p.

and mixed m.p. 194° (lit.ll^ 196 - 197°).(ii) Unreacted diphenylsulphoxide (0.8 g.).

(iii) 2,2-Diphenyl-3-(3,4,5,6 -tetraphenyl-pyrid-2-on-l-yl)- oxathiaziridine monohydrate (0.25 g., 33%). Recrystallisation

from ethanol gave colourless plates, m.p. 154°. Solidification occurred at 169 - 170° with remelting at 220 - 221° (Found: C, 77.9;H, 5.1; N, 4.4; S, 5.0. C4 1H32N2 SO3 requires: C, 77.8; H, 5.1;N, 4.4; S, 5.1%).

% a x * 3500 (-0H), 1640 (amide C=0); 1590; 1570; 1525; 1470; 1310;1240; 1180; 1000; 955; 8 6 8 ; 765; 750; 730; 715 - 690 cm."^.

Xmax * ^37 (log e 4.52), 264 (4.3), 275 (4.16), 349 nm (4.03).PMR: T 6.57 singlet, (2 protons, H2O); 2.1 - 3.2 t multiplet,

(30 aromatic protons).m/e: 614 (P), 414 (P-(Ph)2S0 ), 398, 384, 355, 296, 219, 202 (Ph^.SO),

196, 178.

A sample of the sulphoximine was heated at its melting point for 30 sec. Slow solidification occurred. In the i.r. spectrum of the product there was no -OH band (3500 cm. ^) and the rest of the

spectrum was identical to that of the monohydrate. In the PMR spectrum the singlet at 6.57 t due to one molecule of water had

disappeared.

127

(iv) 3,4,5,6-Tetraphenyl-2-pyridone (50 mg.) contaminated

with the sulphoximine.

(e) In the presence of Methylphenylsulphoxide. Methylphenylsulphoxide was prepared by the periodate oxidation

of thioanisole using the method of Johnson and Keiser.*^*

LTA (0.8 g., 1.8 mmole) was added to a solution of the N-aminopyridone (0.7 g., 1.7 mmole) and methylphenylsulphoxide (1.8 g., 13 mmole) in methylene chloride (40 ml.). The reaction was stirred for 1 2 hr. and the crude reaction mixture was adsorbed onto neutral alumina and chromatographed. Ether/petrol (2:3) eluted 3,4,5,6-tetraphenylpyridazine (25 mg.). Ether/petrol (3:1) eluted 2-methyl-2-phenyl-3-(3,4,5,6 -tetraphenyl-pyrid-2-on-l-yl)- oxathiaziridine (0.7 g., 75%). Recrystallisation from ethanol gave colourless plates, m.p. 216 - 222°. The melting point was

unaltered after further recrystallisation. (Found: C, 78.0; H, 5.3; N, 5.1; S,5.8 . C3 6H2 8N2SO2 requires: C, 78.2; H, 5.1; N, 5.1;S, 5.8%).

v^ax * 1645 (pyridone C=0); 1600; 1585; 1570; 1520; 1490; 1305;1220; 1175; 1010; 995; 960; 760; 700 cm.” .

Xmax : 238 (log e 4.35), 259 (4.16), 342 nm (4.06).PMR: T 6,15 singlet, (3 methyl protons); 2.0-3.3 multiplet,(25

aromatic protons).(f) In the presence of diphenylsulphide.

LTA (0.65 g., 1*4 mmole) was added over 2 min. to a stirred

128

solution of the N-aminopyridone (0,5 g., 13 mmole) and diphenyl

sulphide (1 . 0 g., 6 mmole) in methylene chloride (20 ml.). After

stirring for 16 hr. the reaction mixture was chromatographed on

neutral alumina to give:(i) 3,4,5,6—tetraphenylpyridazine (90 mg., 23%); m.p.

and mixed m.p. 194 - 195°.(ii) 3,4,5,6-Tetraphenyl-2-pyridone (230 mg, 42%), m.p.

and mixed m.p. 268 - 270°.Unchanged diphenylsulphide (0.95 g.) was also recovered. No adduct could be isolated.

4. Pyrolysis of N-(3,4,5,6-tetraphenylpyrid-2-on-l-yl)-dimethylsulphoximine.(a) Alone.The sulphoximine (120 mg.) was heated at 270° in an open

glass sublimation tube for 10 min. giving a dark-brown tar.

Dimethyl sulphoxide (4.5 mg.) distilled up the tube and was collected.

Chromatography of the residue on neutral alumina gave:

(i) Tetracyclone (2 mg., 4%), m.p. and mixed m.p. 216 -

218° (after sublimation).(ii) 3 ,4,5,6—Tetraphenylpyridazine (5 mg., 9.5%), m.p. and

mixed m.p. 193 - 195° (after sublimation).(iii) 3,4,5,6-Tetraphenyl-2-pyridone (40 mg., 43%), m.p. and

129

mixed m.p. 270 - 272°.Sublimation of the sulphoximine at 205°/0.1 mm for 18 hr. then 250°/0.1 mm for 4 hr. gave approximately the same yield of the

same products.

(b) In Decalin.The sulphoximine (250 mg.) was heated in dry decalin (10 ml.)

at 194° for 4 hr. giving a deep red solution. The solvent was

distilled off and the residue chromatographed on neutral alumina giving:

(i) Tetracyclone (trace amount only).(ii) 3,4,5,6 -Tetraphenylpyridazine (40 mg., 30%), m.p. and mixed m.p. 195 - 196°.(iii) 3,4,5,6-Tetraphenyl-2-pyridone (63 mg., 27%), m.p.

and mixed m.p. 270 - 272°.

5. Photolysis of the sulphoximine.(a) Alone.

The sulphoximine (0.5 g.) was photolysed in a quartz tube

in a Rayonet Photochemical Reactor for 3 days using methylene chloride, acetonitrile and acetone (1:1:0.1) as solvent. After

this time negligible change had occurred (TLC), the only product

being a small amount of the parent «-pyridone.

130

(b) In the presence of cyclohexene.The sulphoximine (0.5 g.) was dissolved in a mixture of

benzene, methylene chloride, acetone and cyclohexene (1 :1 :0 .1 :2 ,

30 ml.) and photolysed in a quartz tube for 9 hr. in a Rayonet Photochemical Reactor. Chromatography of the resulting mixture

on neutral alumina gave:(i) 2-(3,4,5,6-Tetraphenylpyrid-2-on-l-yl)-7-azabicyclo-[4,l,0]-heptane, (174 mg., 35%), m.p. and mixed m.p. 219 - 220°.

An i.r. spectrum was identical to that of the product obtained in experiment 3(c) above.

(ii) 3,4,5,6-Tetraphenyl-2-pyridone (100 mg., 26%), m.p. and mixed m.p. 270 - 272°.

3,4,5,6-Tetraphenylpyridazine.

The method of preparation was essentially that of Carboni and Lindsay

3,6 -Diphenyl-l,2,4,5-sym-tetrazine (40 mg.), and tolan (330 mg.)

were heated together at 150° for 3 days. Chromatography of the

resulting mixture on silica-gel, eluting with ether/petrol (1 :1 ),

afforded 3 , 5 ,6-tetraphenylpyridazine (15 mg., 21%) as colourless needles, m.p. 195 - 196° (lit. ^ , 196 - 197°).

151

6 , l-Amino-4 j5. -diphenyl-2-pyridone.

4,6-Diphenyl-2-pyrone was prepared by the method of Arndt and Eisert}^5

Ethyl benzoylacetate (40 g.) in conc. sulphuric acid (40 g.) was stirred at room temperature for 6 days. The mixture

was poured onto ice (400 ml.) and methanol was added to clarify the suspension. A deep yellow precipitate remained, which was filtered off and recrystallised from ethanol giving yellow needles (6.0 g., 24%) of 4,6 -diphenyl-2-pyrone, m.p. 137 - 138° (litî^^^138 - 138.5°).

The pyrone (1.0 g.) in ethanol (60 ml.) was treated with hydrazine hydrate (10 ml., 25% solution) and the mixture was refluxed for 8 hr. On pouring into water (150 ml.) containing

a few drops of conc. HCl, a white precipitate formed which was filtered off and recrystallised from benzene/methylene chloride giving l-amino-4,6 -diphenyl-2-pyridone (0.4 g., 35%) as colourless needles, m.p. 164 - 165° (Found: C, 77.8; H, 5.4; N, 10.8.

C17H14N2O requires: C, 77.8; H, 5.4; N, 10.8%).

Vmax * 3300' 3400 doublet (-NH2 ); 1640 (amide C=0); 1595; 1570; 1545; 1505; 1215; 1060; 1020; 860; 810; 780; 760; 695 cm.“ .

^max * 335 (log e 3.95), 275 (4.04), 249 nm (4.3).PMR: T 4.72 broad singlet, (2 protons, -NH2 ); 3.56 doublet,

1 proton,pyridone ring); 3.15 doublet,(1 proton,pyridone ring);

152

2.5 broad singlet, (10 aromatic protons).

Oxidation.

LTA (0.6 g.) was added to a solution of the N-aminopyridone (300 mg.) in methylene chloride (100 ml.). The mixture was

stirred for 1 2 hr. then chromatographed on neutral alumina to give:

(i) 3,5-Diphenylpyridazine (30 mg., 9%) as colourless needles, m.p. 142 - 143° (litl^^ , 147 - 148°) (Found: C, 82.6;H, 5.2; N, 12.0; m/e 232. Calc, for Ci6Hi2N2:C,tt-5-H,5 .2; N, 12.1%;

MW 232).Vmax : 1595 (C*N); 1580 (C=C); 1500; 1410; 1080; 910; 770;745; 695 cm.“ .m/e: 232, 203, 202, 173, 171, 129, 102, 76.

7. 1-Amino-4,5,6-triphenyl-2-pyridone.4,5,6-Triphenyl-2-pyrone was prepared by the method of

Soliman and El-Kholy.^^^Deoxybenzoin (5.6 g.) and ethyl phenylpropiolate (5 g.) were

successively added to a suspension of sodium ethoxide (1.95 g.)

in ether (40 ml.). The mixture was stored at 0° for 2 days, then

poured into water (250 ml.). Recrystallisation of the precipitate

from acetic acid gave the pyrone as pale yellow crystals (4.5 g.,

, m.p. 250 - 250.5° (litl^?, 246°).

155

Hydrazine hydrate (10 ml., 25% solution) was added to a solution of the pyrone (1 g.) in ethyl cellosolve (60 ml.).The solution was stirred at 80 - 90° (bath) for 16 hr., then

the solvent was evaporated off. Crystallisation of the residue

from ethanol gave l-amino-4,5,6 -triphenyl-2-pyridone, (0.4 g.,

36%), as stout colourless needles, m.p. 196.5 - 197° ( l i t , 199°). Deamination of the N-aminopyridone with sodium nitrite in acetic acid at 0° gave the corresponding pyridone (82%), m.p. 278 - 279° (lit.lig 277°).Oxidation.

LTA (0.67 g.) was added to a solution of the N-aminopyridone (0.5 g.) in methylene chloride (50 ml.) and the mixture was stirred for 16 hr. at 25°. Chromatography of the crude product on neutral alumina, eluting with ether/petrol mixtures, gave:

(i) 3,4,5-Triphenylpyridazine (30 mg., 7%) as pale yellowcrystals, m.p. 254 - 255° (Found: C, 86.2; H, 4.9; N, 9.2.

^22^16^2 requires: C, 86.0; H, 4,9; N, 9.1%).Vmax : 1600, 1555 (C=N, C»C); 1500; 1340; 1320; 1080; 1035;755; 710 - 700 cm.’ .

^max.* ^53 (log e 4.34), 280 nm (shoulder, 4.05).

(ii) 4,5,6-Triphenyl-2-pyridone (277 mg., 58%), m.p. and

mixed m.p. 276 - 277° (litV®, 277°).

154

8 . 5-Aminophenanthridin-6-one.

Sodium hydride (0.6 g., 50% emulsion) was added to a suspension

of phenanthridone (1.5 g.) in methylene chloride (50 ml.) and the

mixture was refluxed for 3 hr. Chloramine (0.63 g.) in ether

(60 ml.) was added to the suspension at 2 0 ° and stirring was

continued overnight. The insoluble residue was then filtered off

and washed with methylene chloride. The combined filtrate and

washings were evaporated almost to dryness when crystallisation

occurred rapidly. Recrystallisation of the product (0.45 g., 30%)

from benzene/petrol (2 :1 ) gave 5-aminophenanthridin-6-one as pale

fawn needles, m.p. 175 - 176° (Found: C, 74.3; H, 4.8; N, 13.3;

m/e 210. C 1 3H1 0N 2 O requires: C, 74.3; H, 4.8; N, 13.3%; MW 210).

vâx : 3300, 3195 (-NH%); 1630 (C=0âmide); 1600; 1575; 1350;

1175; 950; 730 cm.

Xâx : 239 (log e 4.53), 260 (4.33), 325 (3.82), 335 nm (3.81).

PMR: T 4*98 singlet, (2 pro tons ,-IIH2 ) ; 1* 6-2* 85 multiplet, (8 aromatic protons),

m/e: 210, 195, 181, 166, 152, 140, 105.

Phenanthridone (0.8 g.) was recovered from the insoluble residue.

Treatment of the N-aminophenanthridone (50 mg.) with sodium

nitrite (17 mg.) in acetic acid (5 ml.) gave phenanthridone (45 mg.,

8 8 %), m.p. and mixed m.p. 290 - 291°(lit}^ 293°).

155

Oxidation with LTA.

(a) Alone.5-Aminophenanthridin-6-one (50 mg.) in methylene chloride

(20 ml.) was added dropwise to a suspension of LTA (0.15 g.) in methylene chloride (20 ml.). After 16 hr. the reaction mixture was chromatographed on silica-gel to give;

(i) 3,4-Benzocoumarin (15 mg., 31%), m.p. and mixed m.p. 92 - 92.5° (lit\°® , 92.5°). An i.r. spectrum was identical with that of an authentic specimen(ii) Phenanthridone (20 mg.), m.p. and mixed m.p. 288 -

290° (lit. ^ , 293°).Fluorenone was found to be stable to these conditions.(b) In dimethylsulphoxide.

An oxidation of the amino compound (250 mg.) in DMSG gave after the usual work up, N-(phenanthridin-6-on-5-yl)-dimethylsulphoximine (244 mg., 73%), as a fawn powder, m.p. 211 - 212°

(dec.) (Found; C, 62.8; H, 4.8; N, 9.4; S, 10.9. C15H14N2SO2requires: C, 62.9; H, 4.9; N, 9.8; S, 11.2%).

% a x * 1555 (amide C=0); 1620; 1320; 1310; 1200; 1070; 1050 (doublet, S=0); 960; 870; 745; 725 cm.“l.

PMR: T 6.62 singlet,(6 methyl protons); 1.75 - 2.7 multiplet, (8

aromatic protons).The sulphoximine (120 mg.) was pyrolysed at 200°/0.1 mm for

136

4 hr. Phenanthridone (40 mg.) was recovered, the residue

being a black polymeric "coke". TLC did not reveal any fluorenone or benzo-[c]-cinnoline, but only traces of phenanthridone.

9. l-Amino-2,3-diphenyl-4-quinolone.2,3-Diphenyl-4-quinolone was prepared by a modification

of the method of Singh and Mazumdar?^^A mixture of desoxybenzoin (10 g.) and anthranilic acid (8 g.)

was stirred at 130 - 150° in an open flask for 3 days. Theresulting brown tar was cooled to 90° and poured into ethanol (200 ml.) precipitating colourless crystals, which were filtered off and washed with a little ethanol. The product (2.6 g., 16%)had m.p. 335 - 337° (lit.^^\ 333°).

Sodium hydride (0.9 g., 20 mmole) was added to a suspension of the quinolone (4.2 g., 15 mmole) in methylene chloride (50 ml.) The mixture was refluxed for 20 hr., then cooled to 20°, and chloramine (2.3 g., 45 mmole) in ether (235 ml.) was added.

After stirring for 20 hr. the mixture was filtered and the

residue washed with methylene chloride. Evaporation of the filtrate to a small volume and addition of petrol precipitated1-amino-2,3-diphenyl-4-quinolone (0.8 g., 18%). Recrystallisation from ethanol/water (2:1) gave cream plates, m.p. 218 - 219°

(Found: C, 80.3; H, 5.2; N, 8.6. C2 1H16N2O requires: C, 80.7;

137

H, 5.1; N, 8.9%).

' max * 3330» 3200 (-NH2 ); 1630 (C=0); 1610; 1600; 1590; 1550;1530; 1440; 1325; 1165; 1140; 1030; 960; 890; 860; 750; 700 cm."^.

Xmax * ^54 (log e 4.41), 342 nm (4.08).PMR: T 5.52 singlet,(2 protons, -NH2 ); 2.75 - 2.95 multiplet,(14 aromatic protons) .Oxidation.

The 1^-aminoquinolone (0.5 g., 16 mmole) was oxidised with LTA (18 mmole) in methylene chloride (40 ml.). Chromatography of the reaction mixture on silica-gel eluting with ether/petrol (1:1) afforded bis-(2,3-diphenylquinolin-4-on-l-yl) (0.3 g.,63%). Recrystallisation from aqueous ethanol gave pale yellow needles, m.p. 158.5 - 159° (Found: C, 85.4; H, 4.7; N, 4.9;

MW (osmometer) 600. C42H2 8N2O2 requires: C, 85.1; H, 4.7; N, 4.7%;MW 592).

V ^ : 1620, 1580 (C=0); 1595; 1570; 1120; 965; 770; 710; 700 cm."^.

Xmax * ^^5 (log e 4.76), 322 nm (3.92). m/e; 296 (P), 278, 267, 147, 146, 145, 138.

Elution with ether gave deaminated starting material (50 mg.), m.p.333 - 334° (lit.^^\ 333°).

10. l-Amino-6-methy1-3,4,5-triphenyl-2-pyridone.

6-Methyl-3,4,5-triphenyl-2-pyridone was prepared by the

138

method of Wajon and A r e n s

A mixture of «-benzoyl benzylcyanide (11 g.), phenylacetone

(6 g.), acetic acid (30 ml.) and conc. sulphuric acid (8 ml.) was

refluxed for 16 hr. until gas evolution ceased. The mixture was cooled and neutralised with saturated sodium carbonate solution

giving a brown solid. Trituration with acetone and recrystallisation from acetic acid/water (2:1) gave fawn crystals (4.1 g., 40%), m.p. 308 - 310° (lit. ^ , 300 - 302°).

Amination of the pyridone (1.0 g.) in methylene chloride (50 ml.) with chloramine (0.15 g.) in ether (13.5 ml.) and the usual work up procedure gave l-amino- 6 methyl-3,4,5-triphenyl-2-pyridone (0.13 g., 12%) as cream needles, m.p. 238 - 240° (dec.) (Found: C, 85.7;

H, 5.9; N, 8.2. C21+H2 0N2O requires: C, 85.7; H, 5.9; N, 8.3%).

Vmax * 3300, 3190 (-NH2 ) 1640 (pyridone C=0); 1600 (NH2 deformation); 1575, 1545-1530; 1490; 1440; 1075; 1010; 760, 700 (monosubst.

benzene ring) cm.: 231 (loge 4.33), 250 (4.16), 331 nm (3.90).

PMR: T 7.98 broad singlet; 7.78 singlet; 4,45 broad peak; 2,7-3.3 OxHation multiplet.

Oxidation of the N_-aminopyridone with LTA in methylene chloride

gave only deaminated material (25%), m.p. 308 - 310°. No other crystalline products could be isolated.

139


1. Reductive cleavage of bis-(2,3-diphenylquinolin-4-on-l-yl).

Zinc dust (0,2 g.) was added to a refluxing solution of the dimer (40 mg.) in acetic acid (5 ml.) and heating was continued

for 1 hr. The suspension was filtered hot and the acid filtrate diluted with water (2 ml.) causing slow precipitation of 2,3- diphenyl-4-quinolone (38 mg., 97%), m.p. and mixed m.p. 333°.

An i.r. spectrum was identical to that of an authentic specimen.

2. Bis-(3,4,5,6-tetraphenylpyridin-2-on-l-yl).LTA (1.0 g.) was added to a solution of 3,4,5,6-tetraphenyl-

2-pyridone (1.0 g.) in methylene chloride (40 ml.). The mixture was stirred at 20 - 25° for 4 hr., adsorbed directly onto neutral alumina and chromatographed. Elution with ether/petrol (2:3) gave the dimer (110 mg., 11%). Recrystallisation from ethanol gave colourless neèdles, m.p. 244 - 245° (Found: C, 87.4; H, 5.1; N, 3.5.

C58H110N2O2 requires: C, 87.4; H, 5.0; N, 3.5%).Vmax : 1660, 1630 (C=0); 1575; 1555; 1480; 1440; 1400; 1360;1330; 1270; 1220; 1190; 1150; 1100; 1050; 965; 790; 760; 750;700 cm.Xmax : 236 (log e 4.54), 255 (4.48), 275 (4.42), 300 nm (4.30).

Reductive cleavage

Treatment of the dimer with zinc dust in refluxing acetic acid for 5 hr. gave, after work up, 3,4,5,6-tetraphenyl-2-pyridone (62%), m.p. and mixed m.p. 272 - 273°.

140

Discussion

As a possible precursor to 2,3,4,5,6 ,7-hexaphenyldiazaindene (see Section 1), l-amino-3,4,5,6-tetraphenyl-2-pyridone was

synthesised.Attempted characterisation of this N-amino compound by

oxidation with LTA, which was expected to deaminate it, gave rise to a novel intramolecular reaction of the N-nitrene. In order to

determine the generality of this reaction, the work was extended to other 1 -amino derivatives of heavily substituted pyridones.

Preparation of l-amino-3,4,5,6-tetraphenyl-2-pyridone.

From 3,4,5,6-tetraphenyl-2-pyrone.

The preparation of l-amino-2-pyridones by the reaction of

hydrazine hydrate with 2-pyrones is well known,^ ^ ^ a l t h o u g h the mechanism has been little studied. The amine may attack the carbonyl carbon atom as in the conversion of esters to amides, or the 6 -carbon atom, which is conjugated with the carbonyl group; both schemes postulate an open-chain i n t e r m e d i a t e . ^^2

In Route A (see below) ring closure involving the weakly

nucleophilic amide nitrogen would be expected to be less favoured;

in Route B the nucleophilicity of both nitrogens is probably more similar.

141

NH.

B

The 4,6-diphenyl and 4,5,6-triphenyl derivatives of (1) have been prepared by Soliman et al., 117^118 j y reacting the

2-pyrones with hydrazine hydrate in ethanol. The tetraphenyl

derivative has not been reported.3,4,5 ,6-Tetraphenyl-2-pyrone (4) was prepared by peracetic

acid oxidation^ll of tetracyclone (3) and was converted tol-amino-3,4,5,6-tetraphenyl-2-pyridone (5) with hydrazine hydrate in ethanol. A minor product of this reaction was tentatively assigned the seven-membered dihydrodiazepinone structure (6 ) on

the basis of analytical and spectral data.

142

PhNaH*

4i» .

(5)

+ Ph

(6)

The formation of this compound ( 6 ) could arise by the cyclisation of the open-chain intermediate involving the primary and not the secondary amino group.

PhPhPhPh

H(6)

Drew and Pearman found^^S that when substituted phthalimides

were heated with an excess of hydrazine hydrate, phthalazin-1,4- diones were formed, whereas with one equivalent of hydrazine the

products were N-aminonaphthalimides (7) which were converted to the phthalazindiones (8 ) at their melting point.

145

N-H N-NHI equiv.

iequiv.

I-H

However, l-amino-3,4,5,6-tetraphenyl-2-pyridone (5) was quite

stable at its melting point, and was not converted into the diazepinone (6 ) on further heating; it is not surprising that

the analogous ring expansion of a 6 - to a 7-membered ring is disfavoured.

From 3,4,5,6-tetraphenyl-2-pyridone.

This compound was first prepared by Wagon and Arens^^^ by simultaneous hydrolysis and decarboxylation of «-benzoylbenzyl cyanide (9) in a hot mixture of acetic and sulphuric acids.

Following their procedure the pyridone (10) was prepared in 38%

yield. Amination of the pyridone with chloramine gave the ^-amino derivative (50%) identical with that (5) prepared above.

144

Ph-CH-CO-PhICN

>• Ph-CH-CO-Ph H2N-C=0

•Ph-CH-CO-PhCOOH

-CO2> Ph-CH2-C0-Ph

Ph Ph CH» 0=C 1 + CH-Ph

> * 0PhH iK)

C=T:O

Ph

A(lO)

NH^IHONG

rVii (5 )

The N-aminopyridone (5) readily formed a benzylidene derivative, and with sodium nitrite in acetic acid was deaminated to give the

parent pyridone (10, 95%).

Oxidation of l-amino-3,^,5,6-tetraphenyl-2-pyridone.

When the N-aminopyridone (5) was oxidised in methylene

chloride with LTA, gas was evolved, and 3,4,5,6-tetraphenylpyrid=

azine (12, 59%) was isolated. Tetracyclone (3) was detected (TLC)

145

during the oxidation, but could not be isolated. Deamination was

a minor reaction, and 3,4,5,6-tetraphenyl-2-pyridone (18%) was formed,

Carbon monoxide was detected by burning the evolved gas.

4- Ph

(3 )

Ph"Ssl-\hIIO)

An authentic specimen of 3 ,M-,5,6-tetraphenylpyridazine (12)

was prepared, essentially by the method of Carboni and Lindsay,

by reacting 3 ,6-diphenyl-l,2,4,5-tetrazine (11) with diphenyl-

acetylene. More drastic conditions than those reported were

required for this reaction.

§IPh

150

Ph(II) (12)In considering mechanisms for this reaction, the work of

Lemal^^ and of Baumgarten^S is very relevant. They observed the

only recorded examples of intramolecular reactions of N-nitrenes,

where nitrogen was retained in the molecule (see Introduction)

In both cases ring expansion from a five-membered to a stable

six-membered ring occurred.

146

H.O

NH:(13) (14)

By direct comparison with the latter example, the formation

of 3-cinnolinol (14) from 1-amino-oxindole (13), the nitrene (15)

generated from l-amino-3,4,5,6-tetraphenyl-2-pyridone might be

expected to ring expand to the seven-membered diazepinone (16).

PhLTA

Ph

45(15)

Ph

(16)

147

Stabilisation of this intermediate by hydrogen atom

transfer, as occurs in the precursor to 3-cinnolinol, is not

possible, and further reaction would therefore be expected, since (16) contains the unstable «-carbonyl-azo system (see Section 1, Introduction).

The main product from the decomposition of the nitrene (15), 3,4,5,6 -tetraphenylpyridazine (12) would arise from preferential extrusion of carbon monoxide from (16). The product which would be formed on loss of nitrogen, tetracyclone (3), is in fact observed, but appears in only trace amounts.Assuming the intermediacy of the seven-membered «-carbonyl- azo structure (16), the formation of the pyridazine (1 2 ) could

result from a Cope rearrangement followed by loss of carbon monoxide; no such mechanism can be written for the formation of tetra

cyclone (3). Here the loss of nitrogen could be concerted, as shown, or stepwise via a ring-opened intermediate.

PhPh

Ph

Ph

Ph

(12)Ph h

— Nz yPh

148

This mechanistic difference, together with the high stability of the aromatic six-membered pyridazine ring, may account for the

unusual extrusion®^ of carbon monoxide rather than nitrogen in

this fragmentation of an «-carbonyl-azo compound.A possible objection to this mechanism was found when the

postulated dihydrodiazepinone (6 ) was oxidised with LTA. Gas evolution was observed, and tetracyclone was formed, but no tetraphenylpyridazine (1 2 ) could be detected in the product.This is somewhat surprising, as this reaction and the oxidation of l-amino-3,4,5,6-tetraphenyl-2-pyridone, would be expected to give the same intermediate (16) if ring expansion occurs in the latter case.

*11) H A(15) (16) (6 )

However, it should be stressed that the structure (6 ) is a

tentative one, at present.

149

A second product isolated from the oxidation of the

postulated dihydrodiazepinone (6 ) was not fully characterised, but showed two carbonyl peaks in its infra-red spectrum. On gently heating above its melting point, the compound decomposed to give some tetracyclone and unidentified products, suggesting

that this compound may be a tetracyclone adduct (17) of the

«-carbonyl-azo intermediate (16) which, by a retro-Diels Alder reaction gives tetracyclone again on heating (see Section 1, Discussion).

?phf3o

(16)

Ph+

Ph

Ph

Ph(17)

None of the adduct (17) was isolated from the oxidation of the

N-aminopyridone in the presence or absence of tetracyclone.

These observations are by no means conclusive; the postulated

dihydrodiazepinone (6 ) may in fact have a different structure, and be an intermediate in the hydrazine/tetraphenyl-2 -pyrone reaction which contains tetracyclone in a ring-opened form. Thus

only slight doubt is cast on the nitrene ring-expansion mechanism

150

described above.

The intramolecular reaction of the ^-nitrene (15) is

apparently the exact opposite of that predicted by the theories of Lemal, Menger and C o a t s , 1^8 who, from the results obtained

from pyrolysis of a number of l,l-disubstituted-2 -benzene- sulphonylhydrazine salts, concluded that rearrangement of the nitrene (18) to the hydrazone (2 0 ) occurred only in protic solvents where a 1,3-dipolar species (19) could be produced.

CHj.CH. CHjQHiN — N: <-----> A=N

CHj.CH» CHi-dHj08) I

CH,.CH=N-NH.CH&CH; <---- A-NH(20) CHj.CH (19)

When the nitrenes were generated in tetraglyme, there

were no hydroxyl groups available to facilitate this proton transfer from carbon to nitrogen as in the intermediate (19) above, and tetrazene formation resulted. In the protic solvent

diethylene glycol, the major products were the aldehyde

hydrazones.When the sodium salt of l,l-diphenyl-2-benzenesulphonyl-

151

hydrazine (2 1 ) was heated in diethylene glycol or in tetraglyme

only diphenylamine (23) was isolated, which led support to their

proposals, since no 1,3-dipolar species such as (19) can be formed.

? _ A T pN-N-SO,Ph > N-N: — » N-N=N-N --- * PhNHPh/ \ / / \ Ph No*’ Ph Ph Ph

(21 ) (22) (23)

The formation of diphenylamine was thought to proceed by loss of nitrogen from the tetraphenyltetrazene (2 2 ), itself formed either by dimérisation of the nitrene, or by attack of the nitrene on unreacted starting material with subsequent loss of

sodium benzenesulphinate, the latter reaction being the more likely. On the basis of these observations, rearrangement of the tetraphenyl-2 -pyridone-N-nitrene intramolecularly would be

unexpected, and tetrazene formation would be expected in the

aprotic solvent methylene chloride used. The mechanism for the oxidative ring expansion of 1-amino-oxindole to 3-cinnolinol has been concluded by Wittman also to disagree with this hypothesis, as rearrangement occurs in high yield in the aprotic solvent

benzene. He suggests that in this case, even if the concentration

of the 1,3-dipolar species were low in the reaction, rearrangement may still occur if the rate of dimérisation or decomposition of

the nitrene was relatively èlow.Although a 1,3-dipolar form of oxindole-N-nitrene can be

formed, no similar form of 3,4,5,6-tetraphenyl-2-pyridone-N-

nitrene can exist.

152

NH

Evidence that the oxidation of l-amino-3,4,5,6 -tetraphenyl-

2-pyridone with LTA did proceed through a nitrene, was supplied by the following series of experiments.

Oxidation of l-amino-3,4,5,6-tetraphenyl-2-pyridone in the presence of cyclohexene.

A few additions of C-nitrenes to olefins to form aziridines

have been r ep o r t e d , a n d have recently been extended to N-nitrenes in these Laboratories.^^»

The ^-amino-pyridone (5) when oxidised with LTA in the presence of cyclohexene, gave the aziridine (24, 25%). A small amount of tetracyclone , 3 , 4 >5,6-tetraphenylpyridazine (28%),and deaminated starting material (7%) were also isolated.

153

Phs%^^Ph

NH»

(5)

LTA

P h ^ N " ' ^l\|:

(15)

P h ^

suggesting that intramolecular rearrangement of the N-nitrene (15) is rapid compared with intermolecular trapping by the olefin. Previous reported^® yields of aziridines prepared in this way have been >40% when no intramolecular rearrangement occurs No aziridine formation occurred when 1-amino-oxindole (13) was oxidised in the presence of olefins.Oxidation of l-amino3,4,5,6-tetraphenyl-2-pyridone in dimethyl-

sulphoxide.

Dimethyl sulphoxide (DMSO) has been shown^®® to be an effective trap for sulphonyl nitrenes generated by thermolysis and photolysis of arylsulphonyl azides (25).

+ -(CH3)2.S=0 + ArS02N=N=N

(25)

hv/A 0 ► (CH3)2S=N-S02Ar + N2

(25)

The products (26) had characteristic infra-red spectra, with a strong peak at ca. 1040 cm. ^ due to the S=0 stretching f r e q u e n c y .

154

Sauer and Mayer similarly used DMSO to trap C-nitrenes generated by pyrolysis of a series of 3-substituted A^-l,4,2-dioxazolin-5- ones (27).131

CHaJ5Cf— > R - C - N = S = 0 DMSO VR

(27) (28)

The structures of the sulphoximines (28) were confirmed by photolysis of the dioxazolinones (27) in dimethyl sulphide and oxidation of the resulting sulphimines (29) with KMnO^ in acetone.

r-î -n 4 - ‘oO CHg O CH.13

(27) (29)

Oxidation of l-amino-3,4,5,6-tetraphenyl-2-pyridone (5)

with LTA in DMSO gave the dimethylsulphoximine (30, 84%), the

structure being confirmed by analytical and spectral data.

155

LTA

, ; r CHj (30)

The infra-red spectrum of (30) had the characteristic S=0_1peak centred at 1030 cm, and the two S-methyl groups appeared

as a singlet (6,93%) in the PMR spectrum. The mass spectrum of (30) showed initial loss of DMSO (m/e 78) from the parent ion, with peaks for the nitrene (m/e 412), and for tetraphenyl-2 - pyridone (m/e 398),

No other products, particularly of intramolecular rearrangement, could be detected in this reaction, thus proving the efficiency of DMSO as an N-nitrene trap.Pyrolysis of the sulphoximine,

At its melting point (247-248°), the dimethylsulphoximine (30) decomposed slowly, and turned red-brown, A larger-scale

pyrolysis of the pure solid, at 270° for 10 min,, resulted in

the formation of DMSO and, after chromatography of the residue,

tetracyclone (3, 4%), 3,4,5,6 -tetraphenylpyridazine (12, 10%),

and 3,4,5,6-tetraphenyl-2-pyridone (10, 43%),

156

NC H a . ^ = 0

/CHj

(30)

(12)

The fact that these three compounds are also formed in the LTA oxidation of l-amino-3,4,5,6-tetraphenyl-2-pyridone (5) strongly supports the intermediacy of the N-nitrene (15) in both these reactions:

Ph

Ph

CH;5=0

(30)

-DMSOLTA-2H

(15)

(12) + (3) + (lO)

Ph

P h ' ^ N ^NHj

(5 )

The proportions of products are different in the two reactions, but this is not too surprising because of the large difference in the reaction conditions: the room temperature oxidation in

157

solution favours the pyridazine (1 2 ) and the high temperature reaction without solvent favours the pyridone (10), In the

latter reaction, there is an ample supply of active hydrogens in the starting material (30), and the pyridone may be formed by a different mechanism here, possibly involving intramolecular

hydrogen transfer.

Photolysis of the sulphoximine.Photolysis of dimethylsulphoximines in the presence of

olefins has recently been shown in this Laboratory^^^ to give aziridines. Photolysis of the dimethylsulphoximine (30) in the presence of cyclohexene gave the aziridine (24, 35%) identical to that prepared previously by oxidation of the N-aminopyridone (5) in the presence of cyclohexene.

PhPh LTA

O

(30) (24)

158

This reaction again strongly indicates a common intermediate, the N-nitrene (15), in both reactions. However, when the dimethylsulphoximine was photolysed alone under the same conditions, but in the absence of cyclohexene, no decomposition occurred

after 48 hr. This can be explained by the establishment of an equilibrium between the sulphoximine (30), and the nitrene and DMSO upon irradiation, with the sulphoximine strongly favoured.In the presence of cyclohexene the small amount of nitrene formed would be steadily removed as the aziridine (24). On the present

results however, an alternative mechanism involving reaction between excited sulphoximine and cyclohexene without the intermediacy of the N-nitrene, cannot be discounted.

l-Amino-4,6-diphenyl-2-pyridone.4,6 -Diphenyl-2-pyrone was prepared (24%) by cyclisation of

ethyl benzoylacetate in conc. sulphuric acid by the method of

Arndt and Eistert.^^^Condensation of the pyrone with hydrazine hydrate in

ethanol gave the N-aminopyridone (31, 35%).Oxidation of the N-aminopyridone with LTA gave the known^^G

3,5-diphenylpyridazine (32, 9%) as the only pure product.

159

LTA

l-Amino-4,5,6-triphenyl-2-pyridone.

4,5,6-Triphenyl-2-pyrone was prepared from deoxybenzoin

and ethyl phenylpropiolate by the method of Soliman and El Kholy.ll? Condensation of the pyrone with hydrazine hydrate gave the ^-aminopyridone (33, 36%).

Oxidation of the N-aminopyridone (33) with LTA gave3,4,5-triphenylpyridazine (34, 7%) characterised by analytical and spectral data, and 4 ,5,6-triphenyl-2-pyridone (35, 58%) identical with the product obtained by nitrous acid deamination of the N-aminopyridone.

PhPh

NH(33)

PhPhLTA

(34)

Ph

+Ph

(35)

160

l-Amino-6-methyl-3,4,5-triphenyl-2-pyridone.

6-Methyl-3,4,5-triphenyl-2-pyridone (36) was prepared

from «-benzoylbenzyl cyanide and phenylacetone by the method

of Wajon and A r e n s . Amination of the pyridone with chlor

amine gave the î^-amino derivative (37, 12%).

Oxidation of the N-aminopyridone (37) with LTA gave deaminated starting material (25%) as the only pure product.

PhPhK.x^tSs_JPhNH:CI

'' LTA

A iniHi(36) (37)

These last three oxidations clearly illustrate the importance of the four phenyl groups in l-amino-3,4,5,6 -tetra-

phenyl-2-pyridone for rearrangement of the nitrene and

extrusion of carbon monoxide to form the pyridazine. Removal of the 3-phenyl group or both the 3- and 5- phenyl groups

results in a much lower yield of pyridazine, i.e. from about 60% to about 10%. In the former case only, there was a large

compensating increase in the yield of deaminated product.When the 6 -phenyl group was replaced by a methyl group, no

I6l

pyridazine formation was detected, and there was only a small

increase in the yield of deaminated product.There appears to be no simple explanation for these results,

and clearly further work, to establish the importance of steric

and electronic effects, is required.

5-Aminophenanthridin-6-one.

The generality of this unusual ^-nitrene intramolecular reaction was investigated further by the oxidation of 5-àmino- phenanthridin-6 -one (38); this differs from l-amino-3,4,5,6 -tetraphenyl-2-pyridone, by replacing the 3,4-and 5,6-phenyl groups by fused benzene rings. By analogy, oxidation of this compound, by a similar mechanism, would be expected to give benzo-[c]-cinnoline (40) by elimination of carbon monoxide from the seven-membered «-carbonyl-azo intermediate (39), or possibly fluorenone (41) by

loss of nitrogen.

(38)(39)

(41)

162

N-Aminophenanthridone (38) was prepared in 30% yield by

amination of phenanthridone with chloramine. Characterisation

of the product was achieved by deamination with nitrous acid to give phenanthridone (8 8%), and by analytical and spectral data.

Oxidation of (38) with LTA in methylene chloride gave 3,4-benzocoumarin (42, 31%) identical to an authentic specimen; phenanthridone (43, 40%) was also formed by deamination.

NH(38)

LTA/ C H P a ' w =

(42) #3)

The unexpected result, where the molecule has lost nitrogen,

which has, in effect then been replaced by an oxygen atom, is difficult to explain mechanistically. That formation of (42)

did not proceed via fluorenone by a Baeyer-Villiger type of

oxidation was confirmed by subjecting fluorenone to the reaction conditions; it was completely inert. Somewhat surprisingly, no benzocinnoline could be detected. Furthermore no tetraphenyl2 -pyrone was detected in the earlier oxidation of the N-amino-

tetraphenyl-2-pyridone. Thus, the two reactions have taken

165

entirely different courses. The explanation for this may lie in

the very much less favourable nature of the Cope rearrangement in

the phenanthridone case than in the previous monocyclic systems. Here, Cope rearrangement in the analogous intermediate (45) would

require loss of aromaticity of both fused rings. Therefore it seems likely that (45) will be more stable than the earlier «-carbonyl- azo intermediates and, being unable to rearrange intramolecularly, it could be attacked by more LTA as shown:

AcO' Pb(OAc),(44) (45)

(42) HjCOC (pb(OAc), AcO""

This mechanism which requires two moles of LTA was supported by using an excess (4 equiv.) of LTA in the oxidation of (38). The

yield of benzocoumarin increased from the previous 31% to 70%

(not in Experimental).To determine the fate of the nitrene (44) in the absence

of LTA the N-dimethylsulphoximine (46) of phenanthridone was

prepared by oxidation of the N-amino derivative in DMSO.

164

DMSO

NH;

LTA

CH. (46)

■>*

The sulphoximine (46) had a characteristic infrared spectrum (Vg_Q 1050 cm. ^) and the PMR spectrum showed the 'six methyl protons as a singlet ( t 6.62).

Pyrolysis of the sulphoximine, which, by analogy with the N-dimethylsulphoximine of the tetraphenyl-2-pyridone described

earlier, would be expected to generate the nitrene (44), gave

phenanthridone as the only pure product. No benzo-[c]-cinnoline

or fluorenone could be detected in the residue.

1-Amino-2,3-diphenyl-4-quinolone.

An investigation into the reactions of heavily substituted

N-nitrenes in the 4-pyridone series was considered of interest.

165

to discover whether extrusion from a ring-expanded intermediate occurred as in the 2 -pyridone series, or whether a more stable ring-

expanded species could be isolated. The best compound for comparison with l-amino-3,4,5,6 -tetraphenyl-2 -pyridone would have been l-amino-2,3,5,6-tetraphenyl-4-pyridone (47).

Ph

NH.

NHzCf,

fllHi(47, (48) m

However, no route to (47) is known at the present time, and it was decided to look initially at the easily synthesised, closely related l-amino-2,3-diphenyl-4-quinolone (49). This was prepared from desoxybenzoin and anthranilic acid,^^® followed by amination of (48) with chloramine.

If the oxidation were analogous to that of 1-amino pyridones, the N-amino-4-quinolone (49) would be expected to ring expand to the benzodiazepinone (50) which, by analogy with the known^^** dibenzo[c^f]-l,2-diazepin-ll-one (51), a compound stable at 180°,

should be isolable.

165

(4 9 ) NH:

h

(51) (50)However, when the N-aminoquinolone (49) was oxidised with

LTA in methylene chloride, bis-(2,3-diphenyl-quinolin-4-on-l-yl) (55, 63%) was formed. A small amount of deaminated starting material was also isolated.

(49) NH

167

A possible route to (55) is shown. Formation of an unstable tetrazene (53) occurs initially by reaction of the nitrene (52) with starting material, and oxidation of the

resulting tetrazane (R-N-N-R). Loss of nitrogen then gives

the stabilised radical (54) which,instead of abstraction of hydrogen either from the solvent or from acetic acid liberated from the LTA, dlmerises preferentially. The yield of product obtained (63%), appears to rule out initial deamination to the4-quinolone followed by oxidative dimérisation of this species, as only a slight excess of oxidant was used. The structure of the dimer (55) was confirmed by cleavage of the N-N bond with zinc and acetic acid.

(55) Zn/AcOH.

The analogous dimeric species (56) from 3,4,5,6-tetraphenyl-

2-pyridone was prepared (11%) by its oxidation with LTA; zinc

and acetic acid again cleaved the N-N bond in this dimer to reform the pyridone (62%).

168

LTAZnjAcOH

Oxidative dimérisation of secondary amines has been achieved previously^in the carbazole case using KMNO4 in acetone.

Oxathiaziridines.Oxidation of carbenes to the corresponding carbonyl compounds

with dimethyl sulphoxide has been reported^ by Oda e^ al. Dichlorocarbene was oxidised to phosgene, and this reaction

was successful with other carbenes prepared by cleavage of tosylhydrazones with base, the corresponding ketone being

obtained.

;CCl2 + CH 3 -S-CH3 II ^0Ph_

^ C = N - N H T s + CH 3 -S-CH3

CH3 g

CO.CI2 + CH3 .S.CH3

NaOMe Ph.C.CH3 (46%) 0

169

The reaction was thought to involve initial attack of the

carbene on the oxygen of DMSO followed by cleavage of the

S-0 bond:+

:CCl2 + CH 3 -S-CH3 ----> CH 3 -S-CH3 -----> COCI 2 + CH 3 SCH 3

" Lc-ci^ci

The possibility was therefore considered that the

sulphoximines observed in the reaction of our ^-nitrenes with

DMSO could be formed by a similar mechanism. Attack by the

nitrene (57) on the electron-rich oxygen atom of the sulphoxide

could be followed by formation of a three-membered ring (58);

breaking of the N-0 bond would then give the sulphoximine (59).

R-N: + S

0 0 (57) (58) (59)

As far as we are aware there have been no reports that an

oxathiaziridine (58) has been isolated in these, or indeed any

other reactions.

As discussed earlier, generation of N-nitrenes in dimethyl

170

sulphoxide gave excellent yields of sulphoximines. Support

for the structure of these compounds has been obtained from

PMR, and infra-red spectroscopy. The i.r. spectra contain intense peaks due to the S-0 stretching frequency in the same region as the corresponding peaks in dimethyl sulphoxide. The stretching frequency of the S-0 bond in many simple alkyl and aryl substituted sulphoxides has been recently examined^and all occur as intense peaks in the region 1016-1037 cm. (solid state or liquid film).

When 3,4,5,6-tetraphenyl-2-pyridone-^-nitrene (15) was generated in the presence of diphenyl sulphoxide (60), a 1 :1 - adduct was formed (33%) which surprisingly contained no significant peaks in this region of its i.r. spectrum. The oxathiaziridine structure (61) is therefore suggested for this adduct. The adduct was found to be a monohydrate (PMR and i.r.), but was converted into the anhydrous form near its melting point. In

neither form was the S-0 stretching frequency observed in the infra-red.

171

Ph PhPh

(60)(15)

(61) (62)The possibility that increased polarisation of the S-0

bond (62) in the adduct causes obliteration of this characteristic peak appears unlikely. Polarisation of this bond in sulphoxides has been found^^^ to cause only a slight shift of the S-0 absorption band to higher wavelength.

The structure of (61) was supported by other spectral data.The appearance of the characteristic carbonyl stretching frequency at 1640 cm. in the i.r. spectrum showed that the pyridone ring

was still intact. The ultra-violet spectrum was also similar to that of the N-dimethylsulphoximine (30) described earlier. The

mass spectrum of (61) showed the initial loss of a fragment m/e 202 (diphenylsulphoxide) from the parent ion (m/e 614), with

peaks for the tetraphenyl-2-pyridone ring (m/e 398), and diphenylsulphoxide (m/e 202). Pyrolysis of (61) at 250° paralleled

the behaviour of the dimethylsulphoximine (30) except that no detectable (TLC) amount of 3,4,5,6-tetraphenyl-2-pyridone was

formed. In this compound (61) there is no source of active

172

hydrogens to react with the generated nitrene, as was suggested to occur in the dimethylsulphoximine pyrolysis. Tetracyclone,

3,4,5,6-tetraphenylpyridazine, and diphenylsulphoxide were detected (TLC) from the pyrolysis of (61) (not in Experimental).

The novel structure of (61) was therefore clearly supported by this evidence. The N-sulphoximine structure for (61) was disproved by the i.r. evidence by comparison with known 1 - sulphoximines and sulphoxides.

When methylphenyl sulphoxide was used to trap the tetraphenyl-2-pyridone-N-nitrene (15), an intermediate situation was observed. A less intense S-0 peak (centred on 1035 cm. ^) in the i.r. spectrum of the adduct was observed, with an intense

peak at 1 0 1 0 cmi ^ which cannot, with certainty, be assigned; no such peaks appear in the i.r. spectrum of either the sulphoxide

or the tetraphenyl-2 -pyridone.No definite conclusion can be drawn, although it appears

that a mixture of both the oxathiaziridine (64) and sulphoximine form (63) may be present, with (64) predominating.

175

Ph+ *

Ph

CH,(63) (64)

Such a mixture is not unreasonable since methylphenylsulphoxide is structurally intermediate between dimethylsulphoxide, which gives complete sulphoximine formation, and diphenyl sulphoxide which gives exclusive oxathiaziridine formation. The two isomers in the mixtures could not be separated by TLC, but may be the reason for the rather wide melting-point range (6°) of the recrystallised adduct.

An attempted unambiguous synthesis of the diphenyl

sulphoxide adduct (62) by trapping the N-nitrene (15) with diphenyl sulphide, with a view to oxidation of the resulting

sulphimine, was unsuccessful; no adduct could be isolated from

this reaction.

No characteristic infra-red absorption of the oxathiaziridine ring can be definitely assigned, although it was noticed that the i.r. spectra of these and other arylalkyl and diaryl sulphoxide

adducts^?)showed a common, strong, broad peak at 1 2 0 0 -

174

-11250 cm. . By comparison with epoxides, which absorb in this

region due to C-O-C stretching, this peak, presumably due to an N-O-S stretching frequency, can be tentatively assigned to

the three-membered ring system. Attempts are at present being made in these Laboratories to convert the oxathiaziridine adducts into the isomeric sulphoximines.

The observation that N-nitrenes reacted readily with dimethyl sulphoxide to give the sulphoximines but with diphenyl sulphoxide to give the oxathiaziridines can be rationalised on steric grounds. The stereochemistry of the sulphur atom in the sulphoximines will be approximately tetrahedral (e.g. 65) and the C-S-C bond angle

will be approximately 109°, or slightly less due to dipolar repulsion between the S=0 and S=N bonds. In the cyclic form (e.g. 6 6 ) the 0-S-N bond angle will necessarily be much smaller and the C-S-C therefore larger.

" \ A ., - - .s —^ 1 r

^ 4 .

(65) (66)

175

Steric repulsion between bulky groups on sulphur will thus be

relieved more in the cyclic form and this form would therefore accommodate the phenyl rings of the diphenyl sulphoxide derivative better. It is also understandable, on this basis, that the methyl phenyl sulphoxide adduct is intermediate between the other two.

APPENDIX

176

PREPARATION AND REACTIONS OF BIS-(nL-METHOXYPHENYL)-CYCLOPROPENONE

The properties and methods of preparation of substituted cyclopropenones have been intensively studied^O 55 during the

past decade. The stability of the strained cyclopropenone ring

was first predicted^® by Roberts, Streitwieser and Regan by applying molecular orbital calculations to the simplest aromatic system, the cyclopropenylium cation (1 ) and later by Manatt and Robertswho obtained large delocalisation energy values for cyclopropenone (2 ) itself

and its derivatives. Application of the HUckel (4n + 2)n-rule where n = 0 , predicted that these systems would show aromatic stability. The stabilising effect of phenyl groups on the cyclo

propenylium cation was demonstrated^® by Breslow who prepared the mixed fluoroborate-hydroxofluoroborate of the 1,2,3-triphenyl

derivative. The isolation of stable cyclopropenones also verified the early predictions of the stability of this ring

system. Four main methods are available for the synthesis of

177

cyclopropenones, three of which^S'Gl involve the intermediate

formation of the cyclopropene ring which is hydrolysed to the

cyclopropenone. The fourth methodinvolves elimination of

two molecules of hydrogen bromide from «,«'-dibromoketones with triethylamine, the formation of the cyclopropene ring being the final stage in the reaction.

Br BrI ' - EtaN

The last method has been used by Breslow to prepare diphenylcyclopropenone from -dibromodibenzylketone in 45% yield, and is the most attractive method yet discovered for its preparation.

Properties of Cyclopropenones.

To account for their stability it has been suggested^*^^on

the basis of spectral and chemical evidence that the dipolar form (3) contributes considerably to the ground state of cyclo

propenones .

R

178

This is reflected in their basisity, which is greater than

that of other «,3-unsaturated ketones. Di-n-propylcyclopropenone is more basic than diphenylcyclopropenone, the substituent effect here being analogous to that of substituted cyclopropenylium

cations. In the case of diphenylcyclopropenone, crystalline salts can be obtained, and this property can be used as a method of purification.52 Concentrated sulphuric acid precipitates the hydrogen sulphate (4) from the crude reaction mixture, and the cyclopropenone can then be regenerated by treatment.with base.

Ph PI

(HSOJ)>H

(4)Alkaline hydrolysis of cyclopropenones with strong alkali is rapid, yielding «,6-unsaturated acids.

R R

O OH

\H COxH

Cyclopropenones decompose when heated, with loss of

carbon monoxide and formation of the corresponding acetylenes.

179

Diphenylcyclopropenone (m.p. 120°) requires a temperature

higher than 160° to convert it mainly into diphenyl-acetylene.

Below this temperature a dimer is formed for which structure (5) has been suggested.5%

•PhPh

Few carbonyl derivatives of cyclopropenones are known, Diphenylcyclopropenone is reported®^ to form a 2,4-dinitrophenylhydrazone but does not give normal derivatives with hydrazine,^ g-toluene- sulphonylhydrazine,! semicarbazide or hydroxylamine, The latter adds across the C=C bond with the formation of 3,4- diphenylisoxazolone (6 ) and desoxybenzoin oxime (7). Diazomethane adds as a 1,3-dipole to the C«C bond to give 3,5-diphenyl-4- pyridazone (8 ).^^

NHaOH + CH;,— CNOH

(8 ) (6) (7 )

180

Diphenylcyclopropenone has been s h o w n t o react readily with

a variety of activated isocyanates, evolving carbon dioxide and

giving iminocyclopropenes (9) in good yield.

R~N=C=0 4-

spectra.The infra-red spectra of all cyclopropenones show

characteristic peaks at 1830 - 1865 and 1590 - 1660 cm. The longer wavelength absorption was originally assigned^® to the stretching of the C=C bond and the shorter wavelength absorption to the C*0 stretching frequency. Wore recent work based on the solvent dependence of the band positions gives the opposite

assignment.®®,®® The appearance of the carbonyl stretching band

at such a long wavelength indicates the considerable contribution

of the dipolar species (3) to the ground state of cyclopropenones.

The ultra-violet spectrum of diphenylcyclopropenone has been reported to be very similar to that of trans-stilbene.

Japanese workers®® have recently discovered a new low-intensity band at 362 my (e=1150) which moves to lower wavelength in

methanol solution. This they suggest,again strongly indicates

181

the presence of the dipole (3).

Fused Cyclopropenones.Very few ring systems containing a fused cyclopropenone

ring have been reported. Cycloheptenocyclopropenone (11) was synthesised^^ by Breslow and co-workers by dehydrobromination

of 2 ,8-dibromocyclo-octanone (1 0 ) with triethylamine under pressure at 90°. Cycloundecenocyclopropenone (12) was prepared similarly, but cyclohexenocyclopropenone could not be prepared by the same method, presumably because of the much greater angle strain.

(CH^ V o

Benzocyclopropenone has never been isolated, but good

evidence exists for its presence as a short-lived, highly reactive intermediate in certain reactions^? (see Section I).

Attempts to prepare phenanthracyclopropenone (14) by »

dehydrobromination of the ketone (13) have been unsuccessful.G?It was hoped that the higher bond order of the 5,6-double bond

would increase the stability of this fused cyclopropenone system.

182

-H-

(13)When moist benzene was used as the solvent 9-phenanthroic

acid or 9-phenanthroic anhydride were the reaction products.In "anhydrous" conditions only the anhydride was formed. When methanol was used as the solvent for the dehydrobromination, methyl 9-phenanthroate was isolated in high yield. The nature of the intermediate in these reactions, on the basis of results from deuterium labelling experiments, was concluded to be the acyl- triethylammonium bromide (16), which resulted from attack of triethylamine on the intermediate cyclopropenone (15), followed by elimination of a second molecule of hydrogen bromide.

+ Br- CONEtj

183

As phenanthracyclopropenone is theoretically of interest due to the fusion of the cyclopropenone and phenanthrene ring systems,

and also as a possible precursor to 9,10-dehydrophenanthrene, another attempt has now been made to synthesise it by phenolic

oxidation of the appropriate diphenol (17), to give corresponding phenanthracyclopropenone (18) or the bis-dienone (19).

H (18)

(17)

H

(19)An attempt to prepare phenanthracyclopropenone by photolysis

of diphenylcyclopropenone alone and in the presence of iodine has been s h o w n t o give tolan only, by decarboxylation.

184

Boekelheide and Phillips have reported^® the use of phenolicoxidation on the dimethoxymetacyclophane (2 0 ) using ferricchloride or chromic acid to give the bis-dienone (2 1 ) directly.

>CHa

C H

C H .

OCH3(2d (21)

The first step in our investigation was the synthesis of bis- (m-methoxyphenyl)-cyclopropenone. This was prepared in 10% yield by dehydrobromination of l,3-dibromo-l,3-bis-(m-methoxyphenyl)-

propan-2-one with triethylamine. Attempts to precipitate the

hydrogen sulphate salt of the cyclopropenone with sulphuric acid

were unsuccessful. The crude reaction product was purified by extraction with cyclohexane and chromatography. The product had

185

a characteristic infra-red spectrum with intense bands at 1848

and 1620 cm. ^ assigned to the C=C bond and the C*0 group of the

cyclopropenone ring. The structure was proved by decarbonylation with tris-(triphenylphosphine)-chlororhodium-(l)G9 to give 3,3 dimethoxytolan (55%). This reagent has been s h o w n t o convert diphenylcyclopropenone into tolan. An authentic specimen of 3,3'-dimethoxytolan was prepared by mercuric oxide oxidation of 3,3’-dimethoxybenzil-bis-hydrazone.

An initial attempt to oxidise the cyclopropenone using ferric chloride in chloroform was unsuccessful, starting material (95%) being recovered.

As a further investigation into the scope of this oxidation reaction, an attempt was made to couple the phenyl rings of 1,3- bis-(m-methoxyphenyl)-propan-2 -one (2 2 ) using chromic acid, to

give the cycloheptanone (23).

(23)

186

Following the procedure of Boekelheide and Phillips^®, no

reaction occurred after 16 hr., and starting material

was recovered quantitatively.

These results suggest that a system such as the metacyclophanes, which appear to be very suitable for transannular interactions due to the close proximity of the phenyl rings, is necessary if oxidative coupling by this method is to be achieved. However, the phenol (24, R=H) has been reported?^ to couple intramolecularly while the monomethyl ether (24, RaCHg) only dimerises under oxidative conditions.

HO-^ y~oet(24)

Thus oxidative coupling of the ketone (22) may thereforebe more successful using conventional methods.

De-méthylation of bis-(m^-methoxyphenyl)-cyclopropenone was effected with boron tribromide in methylene chloride. The crude product, which appeared to be a mixture of the mono-demethylated

and the fully demethylated derivatives was chromatographed on

silica-gel. As silica-gel is recommended^ for the chromatography of cyclopropenones, no difficulty was expected at this stage.

187

However some decomposition of the mixture did occur during

chromatography as only a few milligrams of the bis-(m-hydroxyphenyl)-cyclopropenone (17) was isolated. Due to the small quantity of material available, only a qualitative experiment

was carried out. A solution of the cyclopropenone (17) in methylene chloride was treated with an excess of silver oxide. After stirring for 16 hr., examination of the mixture (TLC) showed that no oxidation of the cyclopropenone had occurred.

188

1. Preparation of bis-(m-methoxyphenyl)-cyclopropenone.

(a) l,3~Bis(in-methoxyphenyl)-propan~2-one.

This compound was prepared by the method of Hyrd andThomas.74

m-Methoxyphenylacetic acid (10.0 g.), acetic anhydride(10 ml.) and polyphosphoric acid (1 small drop) were refluxed at146 - 147° for 1 hr. Anhydrous sodium acetate (0.7 g.) was thenadded and refluxing was continued for a further 1 hr. The mixturewas then fractioned slowly keeping the vapour temperature below120°. After 2 ml.of distillate had been collected, acetic anhydride(2 ml.) was added to the reaction mixture and the distillation wasrepeated to give 2 ml. of distillate; this was repeated once more.The crude mixture was then distilled under vacuum to give 1,3-bis(m-methoxyphenyl)-propan-2-one (3.97 g., 52%) as a pale yellowoil, b.p. 186 - 188°/0.4 mm. (lit.73, 154 - 158°/0.2 mm.).

V : 3000; 1735, 1620, 1600 (C=0,C=C); 1500; 1265, 1160, 1050max. ' '(C-O-C stretch); 780, 700 (m-disubst. benzene) cm. ^PMR: T 6,37 singlet, (4 protons); 6.32 singlet, (6 protons);

2.62 - 3.35 multiplet, (8 aromatic protons).

(b) 2,5-Bis(m-methoxyphenyl)-3,4-diphenylcyclopentadien-l-one.

l,3-Bis(m-methoxyphenyl)-propan-2-one (0.13 g., 0.5 mmole) and

benzil (0.105 g., 0.5 mmole) were dissolved in refluxing ethanol.

189

Potassium hydroxide (0 . 0 2 g., 0.4 mmole) in ethanol (0.5 ml.)

was added and the mixture was refluxed for 15 min., then cooled in ice and filtered. The deep red crystals were washed with

ethanol (2 ml.). Recrystallisation from benzene/ethanol (1:1) gave 2,5-bis(mrmethoxyphenyl-3,4-diphenylcyclopentadien-l-one (0.115 g., 50%) as deep red needles, m.p. 164 - 165° (Found: C, 83.8; H, 5.4. C3 1H2 4O3 requires: C, 83.8; H, 5.4%)

Vmax : 1725 (C=0): 1600, 1590 (C=C); 1250, 1180 (C-O-C stretch); 1055, 1040; 875; 812; 795; 774; 744; 715; 700; 690 cm."^

(c) Bis-(m-methoxyphenyl)-cyclopropenone.

Bromine (3.2 g., 0.02 mole) in acetic acid (30 ml.) was added to a solution of 1,3-bis-(m-methoxyphenyl)-propan-2-one (2.70 g., 0.01 mole) in acetic acid (15 ml.) over 15 min. at room temperature. The solution was stirred for 5 min. then poured into water (100 ml.) depositing a heavy oil. The mixture was extracted with methylene chloride (2 x 20 ml.) and the extract was washed with dilute sodium hydrogen carbonate solution, then with

water, and dried (MgSOi+). This solution of crude dibromoketone

was added dropwise to triethylamine (5 ml.) in methylene chloride

(10 ml.) over 1 hr. The mixture was stirred for 15 min. then

extracted with hydrochloric acid (3 x 20 ml. 3N). The methylene

chloride was evaporated off, and the impure red gummy residue

190

extracted with boiling cyclohexane (3 x 20 ml.). Chromatography

of the extract on silica-gel eluting with ether/petrol (80:20) removed red impurities. Methanol/ether (1:5) eluted bis-(m- methoxyphenyl)-cyclopropenone (0.25 g., 10%), m.p. 89 - 90°.

Recrystallisation from cyclohexane gave colourless needles, m.p.96 - 96.5° (Found: C, 76.4; H, 5.2. C1 7H1 4O3 requires: C, 76.7;H, 5.3%).

Vmax : 1848 (C=C); 1620 (C=0); 1592; 1585; 1350; 1253, 1230,1030 (C-O-C stretch); 905; 860; 850, 775, 683 (m-disubst. benzene)

“1cm.

Xmax • 234 (log e 4.15), 284 (4.26), 302 (4.15), 310 nm (4.09).PMR: T 6.1 singlet) (6 methoxy protons); 2.5 multiplet,(8 aromatic

protons).

2. Decarbonylation of bis-(m -methoxyphenyl)-cyclopropenone.

Tris-(triphenylphosphine)-chlororhodium-(I) (40 mg.) was added to a refluxing solution of the cyclopropenone (20 mg.) in

benzene (5 ml.). The mixture was refluxed for 3 hr. then chromatographed on silica-gel. Ether/petrol (1:50) eluted 3,3'-dimethoxytolan (10 mg., 55%), m.p. and mixed m.p. 58 - 59°,

and with i.r. spectrum identical with that of an authentic specimen.

3. 3,3*-Dimethoxytolan.(a) 3,3*-Dimethoxybenzil.

m-Methoxy benzaldehyde (32 g.) and sodium cyanide (2.5 g.)

191

were dissolved in a mixture of ethanol (32 ml.) and water (25 ml.), and the mixture was refluxed for 1.5 hr. Water ( 1 0 0 ml.) was added, and the mixture was extracted with ether (2 X 50 ml.). The ether was distilled off, and the residual oil added to a solution of copper sulphate crystals (68 g.) in water (20 ml.). Pyridine (65 ml.) was added, and the mixture was stirred for 2 hr. on a steam bath. Cooling the reaction mixture deposited 3,3’-dimethoxybenzil (15.9 g., 50%). Recrystallisation from carbon tetrachloride gave stout yellow needles m.p. 80 - 81° (lit.7G, 83°).

(b) 3,3*-Dimethoxybenzil-bis-hydrazone.3,3’-Dimethoxybenzil (5 g.), hydrazine hydrate (2.7 g.,

99% solution) and n-propanol (12.5 ml.) were refluxed for 30 hr. The solution was poured into water (150 ml.) forming a sticky gum. Warming the mixture to 50° for 0.5 hr. produced a light brown solid, which was filtered off, washed with ether and recrystallised from aqueous methanol to give 3,3*-dimethoxybenzil- bis-hydrazone (1.8 g., 32%), as pale yellow crystals, m.p. 100 -

101° (Found: C, 64.4; H, 6.0; N, 18.8. C1 5H18N11O2 requires:C, 64.4; H, 6.0; N, 18.8%)

Vmax * 3400, 3200 (-NH2 ); 1600 (C=N); 1560 (C=C); 1430; 1335;1260; 1180; 1040 (C-O-C stretch); 860; 820, 785, 700 (m-disubst. benzene)cm.^

192

PMR: T 6,26 singlet, (6 protons); 4.25 broad singlet, (4 protons); 2.68 - 3.3 multiplet, (8 aromatic protons).

(c) 3,3*-Dimethoxytolan.

The bis-hydrazone (0.7 g.) was oxidised in refluxing xylene (2.2 ml.) with mercuric oxide (1.26 g.) for 1.5 hr. The mixture

was cooled, and petrol (20 ml.) was added. A brown polymeric solid was filtered off and discarded. The filtrates were evaporated to a small volume and extracted with HCl (3 x 10 ml.2N). The acid extract was made alkaline with sodium carbonate and ether extracted. This extract was evaporated to dryness giving 3,3*-dimethoxytolan (0.55 g., 78%), m.p. 59 - 60° (after sublimation) (lit.75, 63 - 63.5°) (Found: C, 80.9; H, 5.9.

C1 6H1 4O2 requires: C, 80.7; H, 5.9%).v^ax • 2100 (C=C); 1610, 1595 (aromatic C=C); 1500; 1260,1040 (C-O-C stretch); 965; 860; 800, 745, 687 (m-disubst. benzene)

-1cm.

PMR: T 6.24 singlet, (6 methyl protons); 2.75 - 3.3 multiplet,

(8 aromatic protons).

4. Déméthylation of bis-(m-methoxyphenyl)-cyclopropenone.

Boron tribromide (153 mg.) in methylene chloride (0.3 ml.) was added to a solution of the cyclopropenone (163 mg.) in methylene

195

chloride (15 ml.). After stirring for 4 hr. at room temperature

the reaction was complete (TLC) and a compound with a lower Rf

had been formed. Water (5 ml.) was added to the reaction mixture

and the methylene chloride solution was washed with water (2 x 10 ml.) and dried (Na^SO^). Evaporation of the solution to dryness followed by trituration with methylene chloride gave a

fawn solid (48 mg.). Chromatography of the crude product on silica-gel eluting with ether/petrol (3:2) gave bis-(m-hydroxyphenyl)-cyclopropenone (8 mg.) as colourless crystals, m.p.118 - 119° (Found: m/e 238. C15H1 0O3 requires: MW 238).

Vmax * 3580, 3460 (-0H); 3150 (bonded -OH); 1840 (C=C, cyclopropenone ring); 1595 (cyclopropenone C=0); 1580; 1445; 1420;1365; 1255; 1240; 1035; 785; 720; 690 cm."^ m/e: 238 (P), 210 (P-CO), 195, 178, 165, 152, 119.

5. Attempted intramolecular oxidative coupling of bis-(m- hydroxyphenyl)-cyclopropenone.

The cyclopropenone (1 mg.) was dissolved in methylene chloride (1.5 ml.) and silver oxide (10 mg.) was added. The solution was stirred overnight at 25° and examined by TLC (silica-gel). No new product could be seen^the cyclopropenone appeared unchanged.

Attempted oxidative coupling of 1,3-bis-(m-methoxyphenyl)-propan-2-one.

The method used was based on that reported by Boekelheide and

194

Phillips.G8

The chromium trioxide reagent was prepared by dissolving '

chromium trioxide (2.67 g.) in water (5 ml.) and adding this solution to sulphuric acid (2.13 g., 98%). The total volume of this solution was made up to 10 ml. with water.

This reagent (2 ml.) was added dropwise to a solution of the ketone (1.8 g., 6 . 6 mmole) in acetone (50 ml.) at 25°. Stirring was continued overnight when TLC examination indicated that no reaction had occurred and starting material was recovered quantitatively.

Attempted intramolecular oxidative coupling of bis-(m-niethoxy-

phenyl)-cyclopropenone.The cyclopropenone (lOO mg.) was dissolved in chloroform

(5 ml.) and anhydrous ferric chloride (0.3 g.) was added. The reaction mixture was stirred overnight at room temperature, then poured into water (10 ml.) and HCl (2 ml. 2N) was added.

The chloroform layer was washéd with water (2 x 10 ml.) and

concentrated, giving unreacted starting material (95%).

195

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some new rearrangements in nitrogen heterocyclic … · cyclopropenones were not formed ......

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