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SYNTHESES AND REACTIONS OF 1-SUBSTITUTED
TRICYC LO 13.2,.1.03' 61 OCTANES
Lei Keng Lon( 李景倫)
A thesis submitted in partial fulfilment of the
requirements for the degree of
Master of Philosophy in
The Chinese University of Hong Kong
1980
Thesis Committee:
Dr. T. Y. Luh, Chairman
Dr. T. L. Chan
Dr. C. N. Lam
Prof. C. Eaborn, External Examiner
CONTENTS
Acknowledgements
Abstract
Introduction
Synthetic Plan
Results and Discussion
Experimental
References
1
2
9
12
45
64
ACKNOWLEDGEMENTS
The author wishes to express his gratitude to Dr. T.Y. Luh
for his invaluable advice, guidance and unfailing encouragement
in the research work and the preparation of this thesis.
He is also indebted to Mr. Y.H. Law and C.P. Yuen for
meesaring mass spectra and 13C-nmr spectra, respectively.
Department of Chemistry, Lei Keng Lon
C. U. H. K.,
June, 1980.
1
ABSTRACT
1-Carboethoxytricyclo[3.2.1.0396]octane was synthesized
from 5-allyl-5-carboethoxy-2-cyclopentenone in-two steps
in excellent yield. Seven other 1-substituted tricyclic
compounds were prepared. The pKa of the corresponding
carboxylic acid was determined in methanol-water (50/50,
v/v) and ethanol-water (50/50, w/w). The selectivity of this
bridgehead radical in the halogen abstraction reaction was
examined. The enhanced acidity of the carboxylic acid and
radical selectivity by comparing with those of related
systems are attributed to the increase of strain in this
system. In addition, solvent assistance was found important
in the acetolysis of 1 tr icyclo[3.2.1.03'6 3octylmethyl
tosylate on the basis of activation parameters and product
distribution.
2
INTRODUCTION
The chemistry of strained ring compounds has been one
of the most popular research area in organic chemistry.1,2
In addition to the challenging synthetic problems involved,
many of these systems have exhibited interesting physical
and chemical properties as well. Tricyclo[3.2.1.0 3,6]octane
(1) (as referred to tricyclooctane below) is an interesting
molecule to be studied because its strain energy is about
25 Kcal/mol higher than that of norborane due to the presence
of the cyclobutane moiety in the former case. This molecule
can also be considered as one of the isomers of bisnor-
adamantane with two carbon atoms less than adamantane.
7
76
12 18
5
8365 3
24 4
(1)
It was not until 19b6 that Sauers and his coworkers3
achieved the first successful synthesis of this hydrocarbon
where the cyclobutyl ring was constructed by a novel ring
closure reaction. Their synthetic route is summarized in
Scheme I.
SCHEME I
Wolff-Kishner
reduction
Na/toluene
ii
Subsequently, a number of tricyclooctane derivatives
have been synthesized. For example, in a closely related
sequence, the ester (3) underwent cyclization on treatment
with potassium t-butoxide to afford 4~substituted
derivatives of tricyclooctane.
4Hunsdiecker
reactio
ICO2 N
Br
Later, Monti and his associates reported the synthesis
of tricyclo[3.2.1.0 3'6Joctan-7-one (4 5 and 6-chloro-
tricyclo[3.2.1.0 3'6]octan-7-one (5)6'7 where the key step
leading to the requisite cyclobutane moiety remains the
intramolecular nucleophilic substitution. Compound (5) is
the first known compound with substituent at bridgehead
position of this tricyclic system. The important reactions
leading to the syntheses of (4) and (5) are listed in
Scheme II and III, respectively.
The chemistry of this tricyclooctane has not been fully
explored. However, the study of reactions involving cationic
intermediates at C-2 has revealed a remarkable resistance to
rearrangement.3 Accordingly, the tosylate (6) and (7) were
synthesized and solvolyzed in buffered acetic acid-3
Surprisingly, exo-acetate (8) was the sole product from
either reaction; and (6) solvolyzed with substantial(10 2'8)
anchimeric assistance in the ionization step.3 Sauers
suggested that it could conveniently be rationalized by
SCHEME II
postulation of nonclassical or rapidly equilibration ions
3formation.
6SCHEME III
0 OBr
Zn/Cu1) .Fe2(CO)9
2) .Br2CH000HBr2
Br
0
cl HCr02Cl1) .Na/EtOH 0MsOMs
2).MsC1,
Et3N
0
C
ButOK
C6H6
(5)
On the other hand, the solvolysis of the tosylate (9)
afforded a rearranged product (10.8 This implies that
rearrangement will readily occur when a carbenium ion is
generated at the C-4 position.
NoAcOTS
OTSH
H
(7)(8)(6)
Interestingly, 2-substitoted tricyclooctanes (11) were
readily obtained from the solvolysis of 2-chlorobisnor-
. 9adamantane 12). Strain energy release was proposed for
this reaction.
The bridgehead reactivities of various compounds have
1 0been studied in detail. However, the syntheses of the
tricyclooctane derivatives with substituent at the bridge¬
head 1-positiori have not been reported. In this work, we
investigated the physical organic chemistry of this tricyclo¬
octane from the viewpoint of free radical chemistry and
carbocation chemistry. In the area of free radical chemistry
we examined the selectivity of the 1-tricyclooctyl radical
in the halogen abstraction reactions. We also studied the
acidity of the carboxylic acid (13) to examine the influence
of the skeletal rigidity on acidity in this tricyclic
system.
In the area of carbocation chemistry, we investigated
the tricyclooctylcarbinyl system (14) to assess the impact
of high strain energies on Wagner-Meerwein rearrangements
and the solvent assistance in the solvolysis of neopentyl
system.
Because both (13) and (14) can be prepared from the
same precursors 1-carboethoxytricyclo [3.2.1.0 5,j octane
(15) by hydrolysis and reduction, respectively, the first
aim in our work is to the synthesis of this highly interest¬
ing compound (15)•
9
SYNTHETIC PLAN
All known procedures3-7 for the preparation of tricyclo-
octane nucleus could not readily be applicable to the
synthesis of (15) because suitable precursors could not
easily be obtained. Consequently, a new, convenient scheme
has to be developed.
The construction of the cyclobutyl ring in (15) can be
viewed as a result from an intramolecular, light induced,
[2+2] symmetry allowed cycloaddition11 of 4-allyl-4-carboethoxy-
nvn1nnentene (16)
CO2C2Hsco caH
[2+2J-COZCXHs
hp
(15)16)
To the best of our knowledge, only two examples have
been reported. The photolyses of prostaglahdine derivative
(17) 12 and 4-methyl-5-allylcyclopentane-1,3-dione-3-enol
acetate (20)13 afforded the tricyclooctane derivatives (18)
and (19) and (21) and (22), respectively. These results
stimulate us to investigate if (15)can also be prepared
10
in the same manner.
0OH
0
OH CsH11CsH11
CO2Me
0hv/THF Cs H11
-78oC
HOH CO2Me Mao2c
H(18)(17)
(19)
o
oby/hexane OAc OAc
Ac0
(22)(21)(20)
The synthesis of (16) is not so straightforward.
However, the cyclopenterione derivative (23) would be much
easier to prepare. Indeed, all known instances described
O
Co2C2H5
(23)
11earlier 12,13 involve the cyclopentenone moiety in cyclo-
addition reaction. Nevertheless, two photoadducts (24) and
(25) would be expected in view of different orientation of
the "exciplex,"14 (26) and (27). This drawback should not
be a difficult problem because either (24) or (25) could
be selectively reduced to (15) with ease.
Co2C2H5CO2C2H5
00[2+2]
(24)(26)
0 0
cozc1H5co2c2H5
[2+2]
(25)(27)
12
RESULTS AND DISCUSSION
I.SYNTHESIS
Our first synthetic target was to prepare the cyclopent-
enone synthon (23). 2-Carboethoxycyclopentanone (28) readily
available from the Dieckmann condensation 15 of diethyl
adipate 16 was chosen as the starting material. 2-Carboethoxy-
cyclopentanone (28) was converted to 2-allyl-2-carboethoxy-
cyclopentanone (29) in 90% yield by treatment with base
followed by allyl bromide.17
00
r.t.
1).ButOK/DMP
C02C2H5
2). allyl bromide,
(29)(28)
A number of method is known to transform saturated
ketone derivatives to the corresponding enones.18,19 One
of the important procedures is d-bromination followed by
dehydrobromination reactions.18 However, the reaction
conditions are generally vigorous and the yield varies.
13These methods could not be applied to our system because
the double bond could be brorninated. Indeed, (29) was treated
with two moles of bromine to give the tribromoproduct (30.20
Br
0
BBr
BrCHC13C02C2
2Br2
02CZrir.t.
(29) (30
Various oxidizing agents such as oxygen in the presence
of transition metal catalysts,19a dichlorodicyanoquinone,19b
pyridine N-oxide-acetic anhydride,19c selenium dioxide,19d,19e
periodic acid19f were found to transform saturated carbonyl
compounds to the corresponding enones but yields vary greatly,
and the effective control of regioselectivity is frequently
a problem.
The ultility and versatility of organoselenium compounds
has become apparent.21 Recently, Reich and his coworkers22
reported that oc, -unsa.turated carbonyl compounds (32) could
be conveniently obtained from the oxidation of a(-arylseleno
carbonyl compounds (31).
The organoselenium compounds (31) can easily be synthesized
by treatment of the enolate of (33) with the arylselenenyl
halide (ArSeX).
Consequently, these methods may provide an alternative
procedure to prepare the desired synthon (23) from (29)• On
treatment with lithium diisopropyl amide (LLA) in the
P T
presence of hexamethylphosphoric triamide (hmpt), 5 (29) was
first converted to enolate (34) which reacted with benzene-
selenenyl bromide to give 5-phenylseleno-2-allyl-2-carboethoxy-
cyclopentanone (35).
Oxidation of the selenide (35) with hydrogen peroxide
afforded a mixtrue of 5-allyl-5~carboethoxy-2-cyclopentenone
(23) and 2-allyl-2-carboethoxycyclopentanone (29) in a ratio
one to one.
The recovered saturated ketone (29) could only be formed
from the selenoxide fragmentation. Detailed mechanism is
unknown. However, approximately equal amount of isomeric
trans selenide (36) and cis isomer (37) would be formed
from the selenation reaction because the steric environment
for carboethoxy group and allyl moiety would be about the
same.
If the carboethoxy and the phenylseleno groups are
cis, intramolecular reaction may occur during the course
of oxidation. A plausible mechanism is outlined in Scheme
IV. On the other hand, the trans isomer would not be
possible to proceed via this cyclic transition state (or
intermediate), (38); and therefore, normal syn elimination
would occur in this case. Although no solid evidence supports
this mechanism, the scheme may provide a reasonable
explanation on this observation.
SCHEME IV.
(37) (38)
(29)
(36)
(23)
The structure for the enone (23) was unambiguously
proved on the basis of the pmr spectrum which exhibits two
multiplets at% 6.10 andS 771 ppm correlated to the
olefinic protons in the cyclopentenone moiety. The mass
spectrum which exhibits a molecular ion peak at me 194
and base peak at me 121 is consistent with
the structure.
12Irradiation (400W, medium pressure) of 5-allyl-
5-carboethoxy-2-cyclopentenone (23) led the concurrent
formation of 1-carboethoxytricyclo[3.2.1.0 '3octan-2-one
(24) and 1-carboethoxytricyclo[3•2.1.0 '°}octan-7-one (25)»
(71o, ca. 1 0:1). The isomers were respectively formed from
the dienes (26) and (27) which differ in orientation only.
Attempts to seperate the isomers were not successful.
1 3The isomer ratio was determined by integrating C-nmr
spectra of the mixture with the aid of proton decoupling
without nuclear overhauser effect technique. Compound (24)
would be expected to exhibit eleven different signals for
eleven carbons. On the other hand, compound (25) would
show only nine absorptions because the skeleton possesses
1 3a C symmetry. The C-nmr spectrum for this mixture showed
s
eleven major peaks of equal intensity in addition to six
miner peaks. The eleven major signals which appeared at
£14.2 (CH), 54.6 (C-5), 56.0 (c-4), 58.8 and 40.4 (C-7 and
C-8), 40.9 (C—6), 45.2 (C-5), 60.9 (CH2-0), 65.8 (C-1),
169.9 (C02-), 210.9 (C-2) ppm were assigned to the absorptions
of the unsymmetrical product (24) Six minor signals at
i
£50.1 (C-5 and C-5), 56.0 (C-2 and C-8), 56.4 (C-4), 42.4
(C-6), 61.2 (CH2«0)_ ppm were'believed to be the absorptions
for the minor product (25)• It is noteworthy that the peaks
for C-1, the two carbonyls and methyl carbon were missing
and may be embodied in the absorptions for (24).
In general, the orientation of the £2+2] cycloaddition
of enones to olefins is influenced by electronic and steric
2 Aeffects. If the steric environment is similar, the
orientation of the cycloaddition reaction will depend on
the electron density distribution in the substrates. For
example, compounds (39) and (40) in addition to a small
amount of side products were isolated from the photolysis
of a mixture of isobutene and cyclohexenone in 33% and 6%
.., 25respectively.
Thus, compound (39) is referred to an electronically
correct product where the -carbon of the cyclohexenone
is bonded to the more substituted carbon atom of the olefin.
Moreover, irradiation of the oxa-enone (41) in isobutene
14afforded the electronically correct product (42) only.
Furthermore, similar results were obtained in the
intramolecular [2+2] photocycloaddition reactions. For
example, upon irradiation the electronically correct
product (43) was obtained quantitatively from the substituted
14cyclohexenone (44).14
(44) (45)
The photolysis of the enol acetate (45a) led the
photoproducts (46a) and (47a) with a ratio of seven to
three. However, irradiation of (45b) afforded approximately
1 5equal amount of two isomers (46b) and (47b).
(45) (46)
The latter observation is understandable because the
electronic effect caused by the alkyl substituents at both
ends of the olefinic double bond in the side chain would
be the same. On the other hand, compound (46a) is still an
electronically correct product and was in fact obtained
as the major product. This argument can be supported by
the result of the photolysis of the prostaglandin derivative
(17) where two isomeric products (18) and (19) (44:56)
1 2were obtained. These results, compared with ours, agree
well to the general model of the photocycloaddition reactions.
Without seperation of the isomers, the mixture (24)
and (25) was treated with methyl mercaptan in ether catalyzed
0 26-28by borontrifluoride etherate at 0 C to afford the
corresponding thiolketals (48) and (49)•
Without further purification, the mixture (48) and (49)
29was refluxed with W-2 Raney nickel in ethanol- to yield
1-carboethoxytricyclo[3•2.1.0' J octane (15) in 90$.
The structure of (ip) was unambiguously proved.
1 3particularly, by C-nmr spectrum which exhibits only
nine signals at 614.2 (CH), 34-6 (C-3 and C-5) 35-9
(C-4), 41.0 (C-2 and C-8), 43-2 (C-6), 44.0 (C-7),
53-1 (C-1), 59.9 (CHO), 175-3 (CO) ppm. These spectral
data firmly establish that (15) is a symmetrical molecule.
On treatment with excess lithium aluminium hydride in
50tetrahydrofuran, the ester (15) was converted to
1-hydroxymethyltricyclo[3.2.1.0 Joctane (50) in 89%.
1 3The structure was proved mainly by its C-nmr spectrum
_ -and infrared absorption at r=3368 cm with no band in
the carbonyl region.
The alcohol (50) was reacted with p~toluenesulfonyl
chloride and pyridine to afford the corresponding tosylate
(64) in 4% yield. This compound was used to study the
solvolytic reaction which will be discussed later.
(50) (64)
On treatment with refluxing aqueous sodium hydroxide
solution (20%), the ester(15) was smoothly hydrolyzed to
give the corresponding carboxylic acid (1 5) in 91%.
(15) (15)
Tricyclop.2.1.0' J octane-1-amine hydrochloride (52)
was obtained from tricyclo[3•2.1.0' 3 octane-1-carboxylic
31acid (13) in 71% by Curtius rearrangement.
Attempts to neutralize the amine hydrochloride solution
with base in order to isolate the free amine were not
successful. Instead, decomposed products with unknown
structure were observed. Indeed, various bridgehead amines
The mixture exhibited the following spectral data: ir (neat)
V=3548 cm-1; pmr (CDCl,) S 1• 18-2.05 (7H,m), 2.18-2.72
2.94 (.2H, s), 3.61 (4H,m) ppm, 13C-nmr (CDC1) g 29• 1 (t),
29-9 (.t), 35-0 (d), 35.2 (t), 41.9 (d), 44-9 (t), 45.0 (.t),
46.5 (t), 61.4 (t), 61.7 (s) ppm 9 highest me: 123.
such as 1-tricycloTj.1.1.0 Jheptyl (55) and cubyl amines
(56) were found unstable and underwent homoketonization
leading to decomposition.
By using the Cristol-Firth modified Hunsdiecker
reaction the bridgehead bromide (57) was obtained
in dibromomethane from tricyclo[3.2.1.0 'Joctane-
1-carboxylic acid (13) in 70%.
The reaction is known to proceed via a free radical
32mechanism; hence the smooth transformation as observed
in the tricyclic system may reflect the relative stability
of this highly strained bridgehead radical and will be
discussed later.
Again, the bridgehead chloride (58) could be prepared
32by analogous reaction in carbon tetrachloride. Actually,
a mixture of bromide (57) and chloride (58) was obtained
and seperated by preparative gas chromatography.
It is interesting to note that all compounds with
tricyclo .2.1.0 'h°ctane skeleton exhibited a strong
peak (usually base peak), which may be arised
from three-bond cleavage to lose a fragment.
13The C chemical shifts for 1-substituted tricyclooctane
derivatives are listed in Table I. Assignments were made on
the basis of relative signal intensities and verified by
their off-resonance decoupled spectra and also with the
aid of proton decoupling mode without nuclear overhauser
effect. The most intense peaks were assigned to the doubly
degenerate carbons C-2,8 and C-35? and their assignments.
were confirmed by the observed multiplicities in their
off-resonance decoupled spectra. The remaining four signals
in order of decreasing intensity (presumably due toI,
increased relaxation time) were assigned to C-7 ojo C-4»
C-6 and C-1 which bear two, one and no hydrogen substituents,
respectively. The signals of C-4 and C-7 carbon atoms
(both carry two hydrogen atoms) were differentiated on
the basis of relative substituent shifts compared to the
related bicyc.lo [2. 2. 1 heptane derivatives, whose signals
34have been unequivocally assigned.
It is noted that when an electron-withdrawing substituent
is attached to the bridgehead 1-position of the tricyclooctanes,
the chemical shift of the o(-carbon atom will be more downfield
than that of the other ring carbon atoms. This would be
plausible arised from an inductive effect being transmitted
through the bonding network.
Table I
1 5
C Chemical Shifts (ppm) of 1-Substituted
Tricyclofj•2.1.0 1 octanes in CDC1,5
X
48.8
50.9
52.9
53.1
60.1
60.0
40.5
40.0
40.9
41.0
40.8
40.0
34-9
34.8
34.7
34.6
35-3
33.6
35.9
35.9
35.8
35.9
36.1
34.4
43-1
43.0
43-6
43-2
48.3
40.3
42.6
41-9
44.2
44.0
49.4
41.8
65-4
66.3
182.5
59.9 175.3 14.2
Another significant feature is that the chemical shifts
of all the ring carbon atoms in the tricyclooctane
derivatives appeared at lower field than those of related
54
bicyclo [2.2.1] heptane derivatives (59). This is apparently
attributable to the increase of strain in the tricyclooctane
molecules.
II. pKa MEASUREMENT:
Benzoic acid was employed to check the method. The
pKa obtained agreed well to the literature values.55,36
5 61The pKa of tricyclo [3.2.1.0' Joctane-1-carboxylic acid
(13) was determined in 0% (v) methanol-water and 5Ofo (w)
I
ethanol-water to be 5.89 and 6.52, respectively. Comparing
our results with the previous works on related compounds
in Table II, the tricyclooctane carboxylic acid (13) is
a stronger acid than the bicycloheptane carboxylic acid
(60) and bicyclooctane carboxylic acid (61). This is
consistent with increasing the total strain of the
tricyclooctyl molecule by introducing the cyclobutane
moiety, and thus the s_ character in the tricyclooctane
37C-1 exocyclic orbital is enhanced.
32Table II
The pKa values of Bridgehead Carboxylic Acids
Determined in Various Solvent Systems At 25 C
50% (v) methanol-water 1 50% (w) ethanol-waterCarboxylic Acids
co2H
6.04(a)
cozN
6.87(b)6.26(a)
CO2H
( c)6.525.89(c)
(a) Ref. 38.
(b) Ref. 39, 40.
(c) This study.
Ill, SELECTIVITY STUDY OF HUhSDIECKER REACTION.
By using the Cristol-Firth modified Hunsdiecker
32 33reaction,the procedure of Ruchardt and his coworkers%'
was employed. Thus, tricyclo [3.2.1.0 octane-1-
carhoxylic acid (13) (1 equiv.) was treated with mercuric
oxide (red, 1 equiv.) and bromine (1 equiv.) in carbon
O
tetrachloride (100 equiv.) at 80 C for 1h, a mixture of
the bromide (57) and the chloride (58) was obtained in a
ratio of 41 to 59- results are compared with related
studies as summarized in Table III.
The most striking feature of the results for the
bridgehead radicals in Table III is the large decrease
in selectivity compared to other acyclic and monocyclic
32aliphatic radicals. The decreased steric requirement
of the bridgehead radicals was suggested as one of the
key factors in the lessened selectivity of those
substances mentioned previously. However, it is
surprising to find that the least hindered radicals of
this groiap are the most selective. This can be explicable
by the variation of polar character in the transition
state of the bridgehead radicals for the halogen
abstraction reaction.
Table III
Bridgehead Radicals Selectivity in Halogen
Atom Abstraction Reactions
Radicals Hunsdiecker reaction. 80 C
0.14a'b
fRBr][RCl]
0.48b'c
0.52b
0.72d
1.00b|e
1.05a
(a) Ref. 32. (b) Ref. 33- (c) Ref. 41. (d) This study,
(e) Ref. 43.
(63)
Since chlorine atom is more electronegative than
bromine atom, electron transfer from bridgehead radical
to halogen atom is more favorable in (62). In addition,
the less strained bridgehead radicals would accommodate
the positive charge more readily because the carbenium
ions favor planar geometry. Consequently, less strained
bridgehead radicals give more chloro compound and
become less selective. These arguments may provide a
plausible explanation on the selectivity of bridgehead
radicals in the halogen abstraction reactions as observed
in this study and related reports.99 a
IV. SOLVOLYSIS OF 1-TRICYCLOt.2.1.0?' 6]oCTYLMETHYL TOSYLATE (64):
The solvolysis of the neopentyl derivatives leads to
products derived almost exclusively from a rearranged
carhenium ion or an equivalent intermediate. The timing of
the rearrangement step is of considerable interest and still
opens to controversy. Various groups have favored a concerted
mechanism. Evidence for this argument has been advanced on
44-47 n. .48-50the basis of the absence or only very small amount
of unrearranged products and almost complete inversion of
the migration terminus in a suitably deuterated substrate.
52-54It has been conceded, however, that a stepwise process
would yield similar experimental results, as long as
rearrangement step is fast. Most neopentyl-like rearrangements
have similar rate constants and the even included cases
where conversion of the primary carbenium ion into its
44-56tertiary analogue is expected to be relatively unfavorable.
It was suggested that the rate limiting step would be the
initial ionization and the rate differences could arise
49from inductive and steric effects. However, it was agreed
that, in cases where rearrangement relieves substantial amounts
of ring strain, the process may be concerted or nearly so.
Solvent participation is important in the solvolysis of
simple alkyl derivatives. However, neopentyl systems are
sterically hindered toward nucleophilic attack by solvent
48-51
molecules, although S2 type reactions have been known
•:59in neopentyl derivatives.' Relatively little is known
about medium effect on neopentyl solvolysis, which may have
been underestimated. It; is of interest to investigate the
solvent behavior in the acetolysis of 1-tricyclo [5.2.1.0-
octylmethyl tosylate (64).
The tosylate (64) can be prepared readily from 1-hydroxy-
methyltricycloL3•2.1.0? Joctane (50) by standard procedure
as mentioned previously.
The rates of acetolysis of (64) were measured in anhydrous
48-50 53 56acetic acid. e resu]_ts are summarized in Table IV.
The activation parameters were calculated and also listed in
Table IV.
Table IV
Rates of Acetolvsis cf 1-Tricvclo r?.2.i.o5,6]
octvlmethvl Tosylate (64)
Temperature °C
99.2
111
119
1.050.01
2.33+0.12
3.70+0.29
18.21.5 -32.7+O.I
The rate constants for a series of related neopentyl
solvolytic reactions are outlined in Table V for comparison.
As previously noted, most of rate constants are comparable.
That for the solvolysis of (64) is about six times greater
than that for neopentyl tosylate' and slightly smaller
(0.8 time) than that for 1-bicyclo2.2.1Jheptylmethyl
tosylate at 100 C.
Table V
Relative Rates of Solvolysis of Bridgehead
Carbinyl Tosylate at 100 C
Compounds
(CH5)5CCH2OTs
R e 1. k
a1 .00
b1.3
c
5.5
, d6.7
189.7 6
a). Ref. 56. b). Ref. 49- 0- This study,
d). Ref. 55. e). Ref. 48.
It, is noteworthy that the more strained tosylate (64) reacts
even slower than the less strained norbornyl derivative. It
is particularly interesting to note that the enthalpy of
activation for (64) is somewhat lower than that for related
49systems, and the entropy of activation is much more
49negative than that for other neopentyl derivatives. The
entropy of activation has widely been used as the criterion
65
to distinguish between S,T1 and S„2 processes. Therefore,N N
the large negative entropy of activation for the acetolysis
Of (64) suggests that significant amount of the reaction
may proceed bimolecularly. In other words, nucleophilic
solvent attack on neutral substrate (64) or the corresponding
tight ion-pair (67) may play an important role during the
course of reaction.
This argument agrees well to our result on the product
distribution. Thus, the tosylate (64) was refluxed with
anhydrous acetic acid to give the unrearranged acetate (65)
(34) and the ring expansion product (66) (47%) in addition
to three rearranged minor products whose structures were
not clear. The yield of the primary acetate (65) was unusually
high comparing with known examples. In the previous studies,
the acetolyses of bicyclo [2.1 .l] hexylmethyl tosylate and
49adamantylmethyl tosylate afforded the unrearranged products
(68) and (69) in 2% and 6.8%, respectively. Such discrepancy
is really striking. The relief of steric strain and the form
ation of more stable tertiary carbenium ion. were believed
to be the driving force of the Wagner-Meerwein rearrangement
of the neopenfyl-type system. The difference in strain energy»
between (69) and (66) would be of the order of 1 Kcal on
the basis of the difference of the calculated strain energy
between the respective hydrocarbons. Moreover, the
bridgehead carbenium ion (70)» which is formed from the
rearrangement of the tight ion-pair (67) and will lead to
the product (66), is significantly distorted from planar
structure and. is thus highly unstable. Therefore, the
rearrangement process seems not so favorable in (64) and
the nucleophilic solvent attack would become apparent,
which resulted in increasing yield of (65). Hence, this
tricyclooctane system would be more susceptible to such
nucleophilic attack on because the environment about
in (64) is less sterically hindered than simple
neopentyl counterpart at the reaction site.
Furthermore, the reaction of 1-hydroxymethyltricyclo-
[3 .2.1.0'octane (50) in thionyl chloride at room
temperature afforded only the unrearranged chloride (71)
in 620 yield.
Thus, it revealed that the rearrangement of this tricyclooctane
system might not be a facile process under these mild
conditions. This observation is also in agreement with our
proposal described early in this section.
The nature of neighboring group participation in the
solvolysis of (64) is not clear. However, no internal
return rearranged product (72) was obtained in this study.
This indicates that the ionization step may proceed without
neighboring group participation. In other words, rearrange¬
ment may occur only after the formation of solvent seperated
ion pair (73) or an equivalent entity. The plausible mechanism
for the solvolysis of (64) is outlined in Scheme Y.
In summary, we have described the direct observation of
solvent participation in solvolysis of a neopentyl derivative.
This system is, to the best of our knowledge, the first
SCHEME V
instance amongthe non-heterocyclic neopenty1-like examples (74)?
which exhibits significant nucleophilic solvent assistance
in the solvolytic reactions..
Compound (74) has been found to solvolyze without rearrangement
in dilute hydrochloric acid at a very slow rate due to the
6 2positively charged nitrogen atom.
EXPERIMENTAL
Nuclear magnetic resonance (pmr) spectra were obtained
1 5using JEOL 60-HL Spectrometer (60 MHz). C-nmr spectra
were recorded on a JEOL FX90Q, NMR Spectrometer. Infrared
(ir) spectra were measured on a Perkin-Elmer 283 Infrared
Spectrophotometer, Mass spectra (ms) were determined on a
Vg-7070F Mass Spectrometer. Microanalyses were performed
by the Australian Microanalytical Service, Melbourne.
Melting points (mp) and boiling points (bp) are uncorrected.
Diphenyl diselenide
Diphenyl diselenide was prepared according to literature
method, and the product was recrystallized from
C
methanol before used; mp. 63-64r 22 C1Llit. 63.5 J
2-Allyl-2- carboethoxycyclopentanone (29)
Potassium tertiary butoxide (270 g, 2.4 mol) was mixed
with N,N-dimethyl formamide (1L) to which 2-carboethoxy-
cyclopentanone (312 g, 2 mol) was added under external
cooling (ca. 10°c). Allyl bromide (290 g, 2.4 mol) was then
added dropwise in 2h at 0°C. After the addition was complete,
the mixture was stirred at room temperature for 38h, and
poured onto ice-water mixture, and it was extracted with
diethyl ether (5x500 mL). The combined etheral solution
was washed with water (2x1L), brine solution (1L), dried
over anhydrous magnesium sulfate, filtered, and evaporated
in vacuo, the residue was fractionally distilled to give
5-Allyl-5- carboethoxy-2-cyclopentenone( 25)
Tetrahydrofuran (500mL) was directly distilled under
nitrogen into a 2-L three-necked round bottomed flask,
Diisopropylamine (58.8 mL, 0.274 mol, freshly distilled
from calcium hydride), n-butyl lithium in ether (1.14 M,
240 mL, 0.274 mol), and a mixture of 2-allyl-2-carboethoxy-
cyclopentanone (29) (49 g, 0.25 mol) and hexamethylphosphoric
triamide (88 g, 0.5 mol, freshly distilled from anhydrous
x Obarium oxide) were added in sequence at -78 C. The mixture
(29) (338.2 g, 8656; bp 50-52° [0.1 mm}; lit.17 bp 125
£l 1 mmj); ir (neat) s 170 (CO), 1752 (ester, CO), 1646
(c=c) cm1; pmr (CDCl) 61.21 (3H, t, J=6.7 Hz), 1.57-2.83
(8H, m), 4.10 (2H, q, J=6.7 Hz), 4-84-6.01 (3H, m)ppm;
15C-nmr (CDC1) 513-4 (CH,), 18.9 (C-3), 31-5 (C-4), 37-1
(C-2 or C-9), 37-3 (C-2 or C-9), 59.2 (C-5), 60.6 (CHgO),
118.1 (C=C, terminal), 132.7 (C=C), 170.1 (CO, ester),
215-2 (CO)ppm.
was stirred for 1h at -78 C. Then a solution of benzene-
selenenyl bromide in ether (2.24 M, 125 mL, 0.28 mol,
prepared from diphenyl diselenide(. 45• 7 g 0.14 molj and
bromine 22.4 g, 0.14 mol in dry ether ($25 mL]) was
added in one-portion and stirred for an additional 15 min.
Then hydrochloric acid (1 N, 500 mL) was added and the
mixture was extracted with ether (5500 mL). The combined
organic layers were washed with hydrochloric acid (1 N, 500
mL), sodium bicarbonate solution (5$» 500 mL), water (4x500
mL), brine solution (500 mL), and dried over anhydrous
magnesium sulfate, filtered, and evaporated to give a
brown residue (96.5 g)•
The brown residue (96.5 g) was dissolved in tetrahydro-
furan (600 mL) to which hydrogen peroxide (52$, 252 g, 2.57
mol) in tetrahydrofuran (240 mL) was added slowly at 0 C
over a period of 2h. The mixture was stirred at room
temperature for 8h. Water (1L) was added and extracted with
ether (5500 mL). The etheral solution was washed with
water (21L), brine solution (400 mL), dried over anhydrous
magnesium sulfate, filtered and evaporated in vacuo to give
a brown residue (56 g) which was passed through silica gel
(60 g) eluted with benzene. Further purification by spinning
band distillation gave (25) (7-4 g» 36$ based on recovered
starting material; bp 90-92°C [6mm); ir (neat)j): 1748 (CO,
ester), 1717 (CO), 1646 (C=C, allyl), 1597 (C=C, cyclopent-
—1
enone) cm; pmr (CDC1) Sl.20 (3H, t, J=7.2 Hz), 2.27-3.41
(4H, m), 4-08 (2H, q, J=7-2 Hz), 4.82-5.99 (3H, m), 6.10
(1H, d, t, J1=6 Hz, J2=1.8 Hz), 7-71 (1H, d, t, J =6 Hz,
J2=3 Hz) ppm; C-nmr (CDCl) $14.0 (CH,), 38.5 (C-4 or C-6),
38.7 (C—4 or C-6), 57.3 (C-5), 61.6 (CHgO), 119-1 (t,
terminal carbon of allylic C=C), 152.1 (C-3 or C-7) 152.7
(C-3 or C-7), 163.9 (C-2), 170-3 (GO, ester), 205.2 (CO) ppm;
mss me 194.
Anal. Calcd for C, 68.02; H, 7-26. Found:11 14 5
C, 68.49; H, 1,22.
1-Carboethoxytricyclo (3 ,2.1.0'3octan-2-one (24) and
1-carboethoxytricyclo C5-2.1.O,3octan~7~one (25)
A solution of 5-allyl-5-carboethoxy-2-cyclopentenone
(23) (1 .5 g, 7.7 mmo 1) in tetrahydrofuran (550 mL) was
irradiated (400W, medium pressure, mercury arc lamp, Applied
Photophysics 400LQ) under nitrogen at 0 C for 2-3h in a
pyrex photochemical reactor. The percentage of conversioni
was analyzed by gas chromatography. The solvent was
evaporated in vacuo, the residue was distilled to afford
a mixture of isomers (24) and (25) (1.07 g» 71%» ca. 10:1;
bp 83-85° C (o.06mm Hg)), ir (neat)): 1760 (CO), 1732 (CO,
•• 1
ester) cm, pmr (CDC1) $1.28 (3H, t, J=7.2 Hz), 1.53-2.80
(8H, m), 3.23 (1H, m), 4.22 (2H, q, J=7.2 Hz) ppm; C-nmr
spectral data for (24) s £l 4.2 (CH), 54.6 (C-5), 36.0 (C-4),
38.8 and 40.4 (C-7 and C-8), 40.9 (C-6), 45.2 (C-3), 60.9
(CHO), 65.8 (C-1), 169.9 (CO, ester), 210.9 (CO)ppm;
C-nmr spectral data for (25): S 30.1 (C-3 and C-5)» 36.0
(C-2 and C-8), 36.4 (C-4)» 42.4 (C-6), 61.2 (CHgOj-and the
Thiolketals (48) and (49)
To boron trifluoride etherate complex (10 ml), the
isomeric mixture of 1-carboethoxytricyclo (3• 2 .1 .0' octan-
2-one (24) and 1 -carboethoxytricyclo (3. 2 .1 .0' octan-7-one
(25) (7.5 Si 59 mmol) in dry ether (80 mL) was added at 0 C.
Methyl mercaptan (6 mL, 108 mmol, condensed at -78 c) was
added, and the mixture was stirred for 2h at room temperature.
Then it was poured into sodium hydroxide solution (10%, 100 mL).
The ether layer was seperated and washed with sodium hydroxide
solution (10%, 2100 mL), water (2x100 mL'), dried over anhydrous
magnesium sulfate, filtered and evaporated in vacuo. The
signals for C-1, two carbonyl carbons and CH-, were not5
observed and may be embodied in the absorption for (24);
ms: me 194.
residue was distilled to give a mixture of (48) and (49)
(9.02 g, 85$; bp 105-1100 [0.05 mm]); ir (neat) p: 1732
(ester, CO) cm pmr (CDCl) 1.26 (3H, t, J=7.0 Hz),
1 .48-2.56 (15H, m, embodied two singlets at 1.88 and 1 .99)9
4.08 (2H, q, J=7.0 Hz) ppm; ms: me 272.
1-Carboethoxytricyclo[5.2.1.0] octane In)
The isomeric mixture of the thiolketals (48) and (49)
(2.0 g, 7 .55 mmol) in absolute ethanol was heated under
reflux With an excess of W-2 Raney nickel catalyst (50 g)
for 4h. The catalyst was filtered and washed thoroughly
with ethanol (200 mL), ana then with benzene (500 mL). The
solvent was removed by evaporation in vacuo to afford a
residue which was distilled to give (15) (1.2 g, 91$;
bp 120-124 C [20mm]); ir (neat): j=1735 cm (CO); pmr
(CDGl) £1.24 (4H, t, CH embodied a multiplet 1H), 1.62
(2H, broad s), 1.71-2.56 (7H, m, embodied a broad s at 1.81),
2.85 (1H, m), 4.08 (2H, q) ppm; 1C-nmr (CDCl) f 14• 2 (CH),
54.6 (C-3 and C-5), 35.9 (0-4), 41.0 (C-2 and Q-8), 43-2
(C-6), 44.0 (0-7), 53.1 (C-1), 59.9 (CH20), 175.3 (CO) ppm;
ms: me 180.1167 (calcd for CHO 180.1150).
i-Hydroxymethyltricyclo[5.2.1. 0' ]octane Alo)
A solution of 1-carboethoxytricyclo[3•2.1.0'octane
(15) (1 -07 g 5-94 mmol) in tetrahydrofuran (10 mL, distilled
from lithium aluminium hydride) was added to a slurry of
lithium aluminium hydride (2 g, 52.7 mmol) in tetrahydrofuran
(30 mL) under nitrogen at 06C. It was stirred at 0°G for an
additional 4h and then at room temperature for 48h. Sodium
sulfate 'solution (10j£, 30 raf) was then added, and solid was
filtered. The solid was washed thoroughly with diethyl ether.
The aqueous layer was extracted with ether (320 mL). The
combined etheral extracts were washed with water (50 mL),
dried over anhydrous magnesium sulfate, filtered, evaporated
and distilled to give (50) (0 •73 g, 890; bp 112-114c [20mm]);
ir (neat): V =3%8 cm-1 (OH); pmr (CDCl) £1.14-1.70 (8H, m,
embodied two singlets at 1.29 and 1.54), 1.94-2.48 (5H, m),
2.79 (1H, m), 576 (2H, s) ppm; C-nmr (CDCl,) £34.8 (C-3 and
C-5), 35-9 (G—4), 40.0 (c-2 and C-8), 42.0 (C-7), 43-0 (C-6),
50.9 (C— 1), 66.3 (CHpO) ppm; ms: me 138.1110 (calcd for
CqH140: 138.1045).
1-TricycloC5.2.1.0' joctylmethyl tosylate Am)
Tosyl chloride (1 g, 524 mmol) was added to a mixture
of 1-hydroxymethyltricyclo [3 .2.1.0'octane (50) (500 mg,
1.97 mmol) in pyridine (7»0 g, 89 mmol, distilled from calcium
)0 at 0 G. The mixture was stirred at room temperature
for five days. It was poured into hydrochloric acid (3N, 100 mL)
and extracted with carbon tetrachloride (2X100 mL). The
combined organic extracts were dried over anhydrous magnesium
sulfate, filtered, and evaporated in vacuo. The residue was
seperated by column chromatography on alumina (basic, EM 1076,
15 g) first eluted with petroleum ether (50-75 C) to recover
the starting alcohol (50) (100 mg), and then eluted with
chloroformpetroleum (1 s 1) to give the tosyl derivative (64)
(92.8 mg, 46io based on unrecovered starting material); pmr
(CDC1)$ 0.70-1.90 (7H, m), 2.10-2.54 (6H, m), 2.82 (1H, m),
4.22 (2H, s), 7.75 (4H, m).
r iTricycloL3.2,1,0' Joctane-1-carboxylic acid (15)
3 61A solution of 1 -carboethoxytricyclo[$. 2 .1 .0' Joctane
(15) (l«3 g 7.22 mmol) in aqueous sodium hydroxide solution
(20$, 75 mL) was heated under reflux for 14h, cooled to room
temperature and washed with ether (200 mL). The aqueous
layer was seperated and neutralized with concentrated
hydrochloric acid (37$, 40 mL) while keeping the temperature
below 5°C. The mixture was then extracted with ether (3x250 mL).
The organic layer was washed with water (200 mL), dried over
anhydrous magnesium sulfate, filtered, and evaporated to
give a colorless solid which was sublimed to yield (1$)
(1.0 g, 91=; mp 106-107°c); ir (KBr:2955, 1696 (CO) cm-1;
pmr (CDC1) $1.10-1.35 (1H, m), 1.71 (2H, s), 1.82-2.71
(7H, mf embodied a singlet at 1 .91), 2.92 (1H, m), 11.92
(1H, s) ppm; 15C-nmr (CDCl) S 34.7 (C-3 and C-5), 35.8
(C-4), 40.9 (C-2 and C-8), 43-4 (C-6), 44.2(c-7), 52.9 (C-1),
182.5 (CO) ppm; ms: me 152.0823 (calcd for 0122''
152.0837).
Anal. Calcd for CH-] 22' 71-03; 795. Found:i.
c, 71.57; h, 8.oo.
1-Tricyclo[3.2,1.0' ctyl amine hydrochloride (52)
A solution of triethylamine (174-9 mg, 1.73 mmol) in
acetone (2.8 mL) was added dropwise to a solution of
tricyclo [3•2.1.0' J octane-1-carboxylic acid (13) (200 mg,
1.32 mmol) in acetone (2.8 mL) and water (0.3 mL) at 0 C.
Ethyl chloroformate (176.2 mg, 1.74 mmol) in acetone (1 mL)
was added dropwise and then stirred for 30 min. A solution of
sodium azide (135 mg, 2.08 mmol) in water (0.6 mL) was
subsequently added and stirred for 2h at 0 C. It was poured
onto ice-water and extracted with chloroform (4x20 mL). The
organic solution was dried over anhydrous sodium sulfate,
filtered, and evaporated to give crude azide (53) (240 mg,
m-Jp=2140 cm) as a yellow oil.
The crude azide (53) in benzene (35 niL) was refluxed for
1h, and benzene was removed by distillation at normal pressure
to give a yellow oil (200 mg) as the crude isocyanate (54)
(i=2280 cm-1).
The crude isocyanate (54) in tetrahydrofuran (10 mL) was
refluxed to which concentrated hydrochloric acid (32%, 5 mL)
was added for 1h and cooled to room temperature and diluted
with water (50 mL), and then washed with ether (2x50 mL).
The aqueous layer was seperated and evaporated in vacuo to
give a colorless solid which was recrystallized from acetone-
methanol to yield (52) (150 mg, 71%; mp 225°C [dec.]); pmr
(DMS0-d6) S1.17-1.27 (1H, m), 1.43-2.38 (9H, m, embodied two
singlets at 1.63 and 1.80), 2.78 (1H, m), 8.73 (3H, broad s) ppm;
15C-nmr (DMSO-dg) $33.6 (C-5 and C-5), 34.4 (C-4), 40.0 (C-2
and C-8), 40.3 (C-6), 41.8 (C-7), 60.0 (C-1) ppm; ms: me
123.1044 (M+-HC1, oalod for CgHN: 123.1048).
1-Bromotricyclo[3.2.1.0 loctane (37)
Tricyclo [3.2.1.0'Joctane-1-carboxylic acid (13) (200
1.52 mmol) and red mercuric oxide (286 mg, 1.32 mmol) in
O
dibromomethane (50 mL) was heated to 80 C and bromine (300 mg,
1.88mmol) was added dropwise and the mixture was refluxed for
2h. Dibromomethane was removed by distillation, n-pentane (200 mL)
was added, and the pentane solution was washed with 1OjS of
sodium hydroxide solution (50 mL), dried over anhydrous magnesium
sulfate, filtered, evaporated and purified by molecular
distillation to give a colorless oil and further purified by
preparative gas chromatography (60 C, 6 FT, SIL. GUM, GE.
XE-60 ON 60-70W AW, DMCS) to give pure bromide (57) (170 mg, 69%);
pmr (CDCl) $1.29-1.59 (1H, m), 1.55 (2H, s), 1.87 (2H, s),
2.08-2.45 (5H, m), 2.71 (1H, m) ppm; 5C-nmr (CDC1 )J35.3
(C-3 and C-5), 36.1 (c-4), 40.8 (C-2 and C-8), 48.3 (C-6),
49.4 (C-7), 60.1 (C-1) ppm; ms; me 186.0065, 188.0033
(oalcd for CgH Br7: 186.0044. calcd for CgHBr: 188.0024).
1-Chlorotricyclo[3.2.1,0]octane (58)
2 C
Tricyclo [3.2.1.0' ]octane-1-carboxylic acid (13) (100 mg,
0.66 mmol) and red mercuric oxide (150 mg, 0.69 mmol) in
carbon tetrachloride (20 mL, distilled from POq) was heated
to 80° C and bromine (160 mg, 1 mmol) in carbon tetrachloride
(5 mL) was added dropwise. The mixture was refluxed for 2h,
then cooled, filtered, evaporated to give a colorless oil which
was a mixture of the bromide (57) and the chloride (58) in a
ratio of 14 to 86 as exhibited on the gas chromatogram. pure
(58) was obtained by preparative gas chromatography (60 C, 6 FT,
1% SIL. GUM. GE XE-60, ON 60-70W. AW. DMCS) as colorless liquid
(60 mg, 61?6); pmr (CDCl) $1.30 (1H, m), 1.54( 2H, s), 1 .78
(2H, s), 1.99-2.41 (5H, m), 2.78 (1H, m) ppm; ms: me 142.0520,
144.0421 (calod for CqHCI55: 142.0549; calcd for CgHCl57:
144.0519).
Selectivity Study of Hunskiecker Reaction of _Lii)
The carboxylic acid (13) (50.6 mg, 0.33 mmol), mercuric
oxide (red, 71-3 mg, 0.33 mmol) in carbon tetrachloride
©
(5•06 g, 33 mmol) was heated to 80 C and then bromine (17 JLL,
0.33 mmol) was added with a microsyringe. The mixture was
refluxed for 1h, and then cooled, filtered, and washed with
carbon tetrachloride (7 mL). The combined organic solution was
washed with sodium hydroxide solution (107$, 10 mL), dried over
anhydrous magnesium sulfate, filtered, and evaporated in vacuo.
The distribution of products was analyzed by gas chromatography
(60 C, 6 FT, 1o SIL. GUM. GE XE-60 ON 60-70W. AW. DMCS).
Analysis of the reaction mixture indicated that the bromide
(37) and chloride (58) were produced in a ratio of 42 to 58,
respectively.
The pKa measurement
(A). 50( v) methanol-water.
The CHEMTRIX TYPE 60A pH meter with BJC pH electrode was
employed for pH measurements. Sodium hydroxide solution was
prepared by dilution of 0.1N aqueous sodium hydroxide solution
with equal volume of methanol, and it was standardized against
potassium acid phthalate. The method was checked by the
35determination of the pKa of benzoic acid. The carboxyiic acid
(13) was dissolved in 5 0% (v) methanol-wat er and titrated with
the standardised sodium hydroxide solution. After each increment
of base was added the solution was stirred for 45 sec followed
by a waiting period of 1 min before the meter was read. The
pKa of the carboxyiic acid (13) was determined by the expression
at 50% neutralization. The results are
summarized in Table VI.
(B). 5¥( w) ethanol-watex-.
The procedure was followed as described before except that
50% (v) methanol-water was replaced by 50% (w) ethanol-water.
The results are listed in Table VII.
Table VI
The pKa of 1-Tricyclo[3.2.1.0'octane-carboxylic
acid (13) in 5 (v) methanol-water at 25 C
Substrate
Benzoic
acid (g)
0.0129
0.0102
Carboxylic
acid (15) (g)
0.0099
0.0078
Sodium Hydroxide Solution
Added at Ofo Neutralization
(mL)a
11 .52
9.10
7.08
5.60
pH observed pKa
5.28t
5.28
5.28
5.28
5.89
5.89
5.89
5.89
-5(a) The concentration of base was 4.5914X10... N.
(b) Ref. 35.
Table VII
The pKa of 1-Tricyclo [3.2.1.0'octane-carboxylic
acid (13) in 50J (w) ethanol-water at 25°C
Substrate
Benzoic
acid (g)
0.0093
0.0088
Carboxylic
acid (13) (g)
0.0102
0.0099
Sodium Hydroxide Solution
Added at neutralization
(mL)a
pH observed pKa.
5-76b
5.76
5.76
5.76
5.76
5-44
5.06
4.92
6.52
6.52
6.52
6.52
-3
(a)The concentration of base was 6.6274X10 N.
(b) Ref. 36.
1 r f) t
Bate of Acetolysis of 1-TricycloL5 .2.1.0' Joctylmethyl Tosylate 164)
The acetolysis was conducted in anhydrous acetic acid
63according to the method of Winstein, Grunwald, and Ingraham.
Anhydrous acetic acid was prepared by adding sufficient
acetic anhydride to react, with the water present in glacial
acetic acid. The mixture was refluxed for 3h, distilled, and
63the distillate was stored in desiccator before used.
Approximately 0.01N perchloric acid in acetic acid was
prepared by dilution of a 72rfo aqueous solution with the
anhydrous acid. This solution was standardized against
potassium acid phthalate to a bromphenol blue end point.
-3Approximately 5x10 N sodium acetate in acetic acid was
prepared by the addition of anhydrous sodium carbonate to
the anhydrous acid and was standardized against perchloric
acid solution. In all titrations, eight drops of bromphenol
blue indicator in the anhydrous acid were used per 3
solution.
The acetolysis was conducted as follow: 4 mL aliquots
of a 6.356X10% solution of the tosyl derivative (64) in
the anhydrous acid were placed in ampoules, which were placed
• «
in three constant temperature baths at 99•2x0.1 C, 111 C.
1190, respectively, single ampoules removed at selected
time intervals, immediately cooled, opened, 3-00 mL aliquots
was pipetted, and titrated against the sodium acetate solution.
The time was computed from the time of opening the ampoules.
The first order rate constants were calculated from the
expression kt= In. (aa-x). The results are summarized in
Tables VIII, IX, and X.
Table VIII
Rate of Acetolysis of tosylate (64) at 99.2t0.Tc
Time, ..sec.
23520
43200
69480
(a-x)x105, Ma
6.080
4.988
3.062
kx10 sec''
1.030
1.059
1.051b
Table IX
Rate of Acetolysis of tosylate (64) at 111 C
Time, sec (a-x)x10, M5 -1
kx10, sec
43290
69524
100590
2.272
1 .178
0.698
2.376
2.425
2.195°
Table X
O
Rate of Acetolysis of tosylate (64) at 119 C
Time, sec
5970
25870
(a-x)xlO5, M
5.054
2.759
kx10, sec
5.905
5-496d
Product Distribution Determination of Acetolysis of Tosylate Am)
Two 25-mg samples of 1 -tricyclo[5• 2 .1. 0 9 octylmethyl
tosyl ate (-64) were placed in two ampoules each containing
5 mL of anhydrous acetic acid. The ampoules were placed in
O
a bath at 119 C for 50h. They were then cooled, opened, and
poured into water. The mixture was extracted with ether. The
ether layer was washed with water, dried over anhydrous
magnesium sulfate, filtered, and evaporated in vacuo. Analysis
of the residue by gas chromatographic method indicated that
the unrearranged acetate (65) and the rearranged acetate (66)
were produced in 57 and 47 respectively, in addition
to three rearranged, minor products whose structures were
not clear. The unrearranged acetate (65) exhibited a singlet
at $416 (CHOAc) in the pmr spectrum and £66.8 (CHOAc) in
1 3addition to eight other absorptions in C-nmr spectrum.
The rearranged acetate (66) showed no absorption below
in pmr spectrum and S 79•9 (C-OAc) and eight other signals
13in C-nmr spectrum.
1-Chioromethyltricyclop.2.1octane .in)
1-Hydroxymet'hyltricyc lo [3• 2 .1. 0' octane (50) (138 m£
1 mmol) was stirred with thionyl chloride (2.5 mL, 34-3 mmol)
at room temperature for 22h. The mixture was poured onto
ice, and then extracted with ether (3x25 mL). The combined
etheral solution was washed with saturated sodium bicarbonate
solution (2x50 mL), water (50 mL), dried over anhydrous
magnesium sulfate, filtered, and evaporated.-The residue was
purified by column chromatography on alumina (basic, 10 g)
o
eluted with petroleum ether (50-75 C) to give (71)
(96 mg, 62°jo) pmr (CDCl)£ 1.12-1.42 (4H m), 1 .46-1 .80 (3H,
m, embodied a singlet at 1.53) 2.04-2.44 (3H, m), 2.76
1 3
(1H,. m), 4.O6 (2H, an AB system, J=10.2 Hz) ppm; C-nmr
(CDC15) S 34.9 (c-3 and C-5), 35.9 (C-4), 40.5 (C-2 and C-8),
42.6 (C-7), 43.1 (C-6), 48.8 (C-1), 65.4 (CHgCl) ppm;
ms: highest me 121 (M+-Cl).
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