bpo c chapter 24

7/29/2019 Bpo c Chapter 24

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24ORGANON TROGENCOMPOUNDSLES, NCOMPOUNDS, AND SOMESUBSTANCES W

N BONDS

Te properties of the simple amides are relevant to th e chem istry of peptidesand proteins, subs tance s that a re fundamental to all life as w e know it. Ind eed,the characteristics of peptides and proteins are primarily due to their poly-amide structures. For this reason, it is important to know and understand thechemistry of simple amides.24-1 STRUCTURAL, PHYSICAL, AND SPECTRAL

CHARACTERISTICS OF AMIDES24-1A Molecu lar S tructureThe structural parameters of the amide group have been determined carefullyand the following diagram gives a reasonable idea of the molecular dimensions:

N-R

bond lengths,A bond angles


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6168 24 Organonitrogen Compounds I I. Amides, Ni tr iles, Ni tro C ompoundsAn important feature of the group is that it is planar-the carbon, oxygen,nitrogen, and the first atom of each of the R groups on carbon and nitrogenlie in the same plane. The 6- N bond distance of 1.34 A is intermediate be-tween the typical single bond C-N distance of 1.47 A and the double bondC=N distance of 1.24 A. This and other evidence indicates that the amidegroup is a hybrid structure of the valence-bond forms l a and I b , with a sta-bilization energy of about 18 kcal mole-l:"0'. .xR :O' R\ ../C-N +---+ \ 0// \R R R R?="\

Coplanarity is required if the dipolar structure Ib is to be significant. Anappreciable dipole moment may be expected of amides and, in fact, simpleamides have dipole moments in the range 3.7-3.8 debye. (For reference, thecarbonyl group has a moment of about 2.7 debye, Section 16-1B.)As a consequence of the polarity of the amide group, the lower-molecular-weight amides are relatively high-melting and water-soluble, ascompared to esters, amines, alcohols, and the like. The few that are liquids,such as N,N-dimethylmethanamide and I-methyl-1-aza-2-cyclopentanone,have excellent solvent properties for both polar and nonpolar substances.Therefore they are good solvents for displacement reactions of the SN ype(Table 8-5).

/OH-C \N(CH:l),N,N-dimethylmethanamide I-methyl- I -aza-2-cyclopentanone(dimethylforma mide) (N-methy lpyrrol done)

Another very important consequence of amide structure is the extensivemolecular association of amides through hydrogen bonding. The relativelynegative oxygens act as the hydrogen acceptors while N-H hydrogens serveas the hydrogen donors:R

R \\ / PR N-H----O=C\ / \ P----.-"R-C \N-H-- - -O=C R \/ \ rR----o=c R\ /NpH----ORR

hydrogen bonding hydrogen bonding(polymeric association) (dimer formation)


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24-1B Nomenclature

Exercise 24-1 Amides with structures l ike the fol lowing are diff icult to prepare andare relatively unstable. Ex plain.

24-1B NomenclatureT h e naming of amides is summ arized in Section 7-7D. T he points to rememberare that they generally are named either as (i) alkanamides , in which theprefix a l kan ( e ) is determined by the longest carbon chain that includes the

0I1carbonyl group (H-C-NH, is me thanam ide), o r as (ii) substituted carbox-

0IIamides , R-C-NH,, in which the name is completed by identifying the Rsubstituent:

benzenecarboxam ide cyclopentanecarboxamide(benzamide)The degree of substitution on the amide nitrogen determines whetherthe am ide is primary, RCONH,, secondary , RCONHR, or tertiary, RCONR,.When the amide is secondary or tertiary, the symbol N for nitrogen) mustprecede the name of each different group attached to nitrogen:

butanamide(primary) N-phenylethanamide N-ethyl-N-methylmethanamide(secondary) (tertiary)


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1170 24 Organonitrogen Compounds II. Amides, Nitriles, Nitro Compounds

Exercise 24-2 a. Name each of the fol lowing comp ounds by the system d escr ibedin this section:

0 0I(i) CH2=CH-C-NH2 (ii) II(i i i) fJNcH(the common nameis acetanilide)

b. Write a structure to represent each compound shown:(i) N-ethyl benzenecarbo xamide(i i) N-cyclohexyl-2-methylpropanamide

24-1C Infrared SpectraConsiderable information is available on the infrared spectra of amides. Byway of exam ple, the spectra of three typical amides w ith different degrees ofsubsti tution on nitrogen ar e show n in Figure 24-1.A strong carbonyl absorption is evident in the spectra of all amides,although the frequency of absorption varies somewhat with the structure ofthe amide. Th us primary amides generally a bsorb near 1680 cm-l, w hereassecondary and ter tiary amides absorb at s l ightly lower frequencies. TheN-H stretching frequencie s of am ides ar e closely similar to those of aminesand show shif ts of 100 cm -l to 200 cm -l to lower frequencies as the result ofhydrogen bonding. Primary amides hav e two N-H bands of medium intensitynear 3500 cm-l and 3400 cm-l, whe reas seconda ry amides, to a f irst approxi-mation, have only on e N-H band near 3440 cm-l. H owe ver, a closer lookreveals tha t the numbe r, posit ion, an d intensity of the N-H band s of mono-substi tuted amides depend on the conformation of the amide, which can beei ther cis o r trans:

Normally, the tran s conformation is m ore stable than the cis conformation forprimary amides. H ow eve r, for cyclic amides ( lactams), in which the r ing sizeis small, the configuration is exclusively cis:


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24-1C lnfrared Spectra

Figure 24-1 lnfrared spectra of propanamide, N-phenylethanamide,and N,N-dimethylmethanamide in chloroform solution. Notice the appear-ance of both free NH bands (sharp, 3300-3500 cm-') and hydrogen-bonded NH bands (broad, 3100-3300 cm-') for primary and secondaryamides.


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1172 24 Organonitrogen Compou nds II. Amides, Nitri les, Nitro Compounds24-1D NMR SpectraT he p ro ton nmr re sonances of the N-H proton s of amides a re different fromany we have d iscussed so fa r . Genera l ly , these will appear a t room tempera-ture as a broad singlet absorpt ion, which may turn into a broad tr iplet a t highertempera tures . A typ ica l example i s propanamide (Figure 24-2).

The broad N-H proton resonance is due to the special nuclear properties of14N, the predominant natural isotope of nitrogen. This is established beyondquestion by observation of the proton spectrum of an amide in which the 14Nis replaced by the lSN isotope to give RC01WH2.In this case the proton linesare sharp. The details of the phenomena that lead to the broad resonances ofthe M-H protons in amides are discussed e1sewhere;l for our purposes itshould suffice to note that the 14N nucleus has much shorter lifetimes for itsmagnetic states than do protons, and the broad lines result from uncertaintiesin the lifetimes of the states associated with 14N-H spin-spin coupling (Sec-tion 27-1). One should be prepared for absorptions of this character in amidesand some other substances with N-H bonds that are not involved in rapidintermolecular proton exchanges. That similar behavior is not observed forthe N-H resonances of aliphatic amines (see Figure 23-5) is the result ofintermolecular proton exchanges, which, when sufficiently rapid, have the effectof averaging the magnetic effects of the 14N atoms to zero:

or0 0RrNH2+ RNH R'NH + RNH,

The situation here is analogous to that discussed previously for the splittingof the resonances of 0-H protons of alcohols by protons on the a carbons(see Section 9-101).T h e nm r spec t ra of amides a re revea ling as to th e s t ruc ture of the amidegroup. For example , the spec t rum of N,N-dimethylmethanamide shows two

three-proton single resonances a t 2.78 p p m a n d 2.95 ppm, which means tha ta t o rd inary tempera tures th e two m ethyl groups on n it rogen a re not in the sam emolecular envi ronment :

Th is i s a consequence of the double-bond chara c te r of the G-N bond expec tedfrom valence-bond structures l a and "I,which leads to restr ic ted rotat ion'9. D. Roberts, N ~ ~ c l e a ragnetic Re son anc e, Applications to Ovgnnic Chem istry,McGraw-Hill Book Co., New York, 1959, Chapter 5. Also see the nmr referencesat the end of Chapter 9 in this'book.


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24-1D N M R Spectra

Figure 24-2 Proton nmr spectr um of p ro pa na m id e, CH,CH,CONH,, inchloroform solution (solvent not shown) at 60 MHz relative to TMS at0.0 ppm

about this linkage. One of the methyl groups (A) has a different stereochemicalrelationship to the carbonyl group than the other methyl group (B). GroupsA and B therefore will have different chemical shifts, provided that rotationabout the C-N bond is slow. However, at 150" the two three-proton lines arefound to coalesce to a single six-proton line, which means that at this tem-perature bond rotation is rapid enough to make the methyl groups essentiallyindistinguishable (see Section 9- 10C):

O A/" " i 0 B~ H ,,\\ rapid at 150" \\ /f""\ ' slow at 25" ' fPN\Id BCH3 El AC .i :I

\Most amides do not rotate freely about the C-N bond. The barrier to thiskind of rotation is about 19 kcal mole-l, which is high enough for the non-equivalence of groups on nitrogen to be observable by spectral techniques,but not quite high enough to allow for actual physical separation of stable E,Zconfigurational isomers.

Exercise 24-3 Show how structures can be deduced for the two substances withthe molecular formulas C,H,N03 and Cl,H13N0 from their infrared and nmr spectra,as given in Figure 24-3.


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l " 1 9 4 24 Organonitrogen Compoun ds 11 Amides, Nitr i les, Nitro Compounds


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24-2 Amides as Acids and Bases

Figure 24-4 Natural-abundance 15N spectrum of N-methylmethanamide,HCONHCH,, taken at 18.2 MHz with proton decoupling. The large andsmall peaks are separated by 2 ppm. See Exercise 24-5.Exercise 24-4 Primary amide s giv e a strong peak at m /e 44 in their mass spectra.Indicate the nature of this peak and suggest how it might be formed.Exercise 24-5" a. The I5N nmr spectrum with proton decoupling (Section 9-101)of N-methylmethanamide (Figure 24-4) shows two c losely spa ced signals of unequalheight. Explain how these peaks arise and what you wo uld exp ect the spectrum to looklike if it were taken at 150".b. The proton-decoupled I5N spectra of lactam s diss olve d in CHCI, show only onepeak when the ring size is 5, 6, 7, 8, 10, and 11, but two une qual pea ks when the ringsize is 9. Account for this behavior. (Review Section 12-7.)

24-2 AMIDES AS ACIDS AND BASES24-2A Acidi tyAmides with N-H bonds are weakly acidic, the usual K , being about 10-16:


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fl76 24 Organonitrogen Com pounds I I . Amides, Nitr i les, Nitro CompoundsNonetheless, amides clearly are far more acidic than ammonia (K, -and this difference reflects a substantial degree of stabilization of the amideanion. However, amides still are very weak acids (about as weak as water) and,for practical purposes, are regarded as neutral compounds.

Where there are tw o carbonyl groups to stabilize the amide anion, as inthe 1,2-benzenedicarboximide (phthalimide) anion (Section 18-1OC), theacidity increases markedly and imides can be converted to their conjugatebases with concentrated aqueous hydroxide ion. We have seen how imide saltscan be used for the synthesis of primary amines (Gabriel synthesis, Section23-9D and Table 23-6).

24-25 Basici tyThe degree of basicity of amides is very much less than that of aliphatic amines.For ethanamide, Kb is about (K, of the conjugate acid is - 10):

N H ~The proton can become attached either to nitrogen or to oxygen, and the choicebetween the assignments is not an easy one. Of course, nitrogen is intrinsicallymore basic than oxygen; but formation of the N-conjugate acid would causeloss of all the amide stabilization energy. Addition to oxygen actually isfavored, but amides are too weakly basic for protonation to occur to any extentin water solution.

Exercise 24-6 Explain how the temperature variation of the proton nmr spectrum ofN,N-dimethylmethanamide in strongly acidic solut ion might be used to decidewhether a mides acc ept a proton on nitrogen or oxygen. Review Section 24-1D.

24-3 SYNTHESIS OF AMIDES

24-3A From Carboxyl c Acid sFormation of amides from carboxylic acid derivatives already has been dis-cussed in some detail (Section 23-9A):


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24-3A Synthesis of Amides from C arboxyl ic A cidsTable 24-1Derivatives and Reactivity of Carboxylic Acids Commonly Usedin Amide Formation

Reactivi ty inpK, of HX am ide formation

-OH HOH-CI HCI- 3 HN3-OCH2CH3 HOCH2CH3

16 Iow a-6 good3 good

16 low

9.89 moderate

7.15 good

4.75 moderate

"At ordinary temperatires, requires activation through a coupling agent (Section23-9A), b ut on strong heat ing can give amide di rect ly.bGood leaving grou p because of stabi l ization of the type

"Good leaving group, possibly because of associated de com posi t ion to more stableproducts

The ease of formation of amides by the reaction of Equation 24-1 depends alot on the nature of the leaving group X. The characteristics of a good leavinggroup were discussed in Sections 8-7C and 8-7D in connection with S, reac-tions, and similar considerations apply here. Some idea of the range of acidderivatives used in amide synthesis can be obtained from Table 24-1, whichlists various RCOX compounds and the pK, values of HX. As a reasonablerule of thumb, the stronger HX is as an acid, the better X is as a leaving group.


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1178 24 Organonitrogen Compounds II. Amides, Nitriles, Nitro CompoundsAmides generally are formed from acid chlorides, acid azides, acid anhydrides,and esters. It is not practical to prepare them directly from an amine and acarboxylic acid without strong heating or unless the reaction is coupled to asecond reaction that "activates" the acid (see Exercise 15-25). Notice thatesters of phenols are more reactive toward amines than esters of alcoholsbecause phenols are stronger acids than alcohols.

24-3B From NitrilesThe hydrolysis of nitriles is a satisfactory method for preparation of unsubsti-tuted amides and is particularly convenient when hydrolysis is induced undermildly basic conditions by hydrogen peroxide (see Exercise 24-8):

NH,dilute base

For the preparation of amides of the type R3CNHCOR, which have atertiary alkyl group bonded to nitrogen, the Ritter reaction of an alcohol oralkene with a nitrile or hydrogen cyanide is highly advantageous. This reactioninvolves formation of a carbocation by action of strong sulfuric acid on analkene or an alcohol (Equation 24-2), combination of the carbocation with theunshared electrons on nitrogen of RCN: (Equation 24-3), and then additionof water (Equation 24-4). We use here the preparation of an N-tert-butylalkan-amide as an example; RC=N can be an alkyl cyanide such as ethanenitrileor hydrogen cyanide itself:


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24-3B Synthesis of Amides from Nitri les

'CH:, CH,Th is reaction also is useful for the preparation of primary amines by hydrolysisof the amide. I t is on e of the relatively few practical methods fo r synthesizingamines with a tert iary alkyl group on the nitrogen:

CH3 0 CH3 0I II I IICH,-C-NH-C-R > CH3-C-NH, + HO-C-RI H@ o r @OHCH3 (reflux) ICH3

Exercise 24-7 a. Draw the two important valence-bond structures for a nitriliumion [RCNR ]@ and w rite the steps involved in hydration of a nitri l ium ion to an amide,RCONHR.b. Would you expect N-methylethanamide to be formed from methanol and ethane-nitr i le in H2S04?Explain.Exercise 24-8 Nitri les are converted readily to amides with hydrogen peroxide indilute sodium hydrox ide solution. The reaction is

The rate equation isWv = k [H2 02] OH] [RC=N]

When hydrogen peroxide labeled with 180H21802)s used in ordinary water (H2I60),the resulting amide is labeled with 180 RC180NH2).

Write a mechanism for this reaction that is consistent with al l the experimentalfacts. Notice that hydrogen perox ide is a weak ac id (K, - 10-12), and in the absen ceof hydrogen perox ide, dilute sod ium hydro xide attacks nitri les very slowly.Exercise 24-9 Show how the following transformations could be achieved: C6H5-CH2C02CH3- 6H,CH2C(CH3),0H -+ C6H5CH2C(CH,),NHCH0. Name the prod-uct by the system used in Section 24-18.


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1180 24 Organoni t rogen Com pounds II. Amides, Nitr i les, Nitro Compounds24-3C The Be ckm ann Rearrangement of OximesYou may recall that ketones react with RNH, compounds to give products\with a double bond to nitrogen, C=NR (Section 16-4C). When the RNH,

/compound is azanol (hydroxylamine), HO-NH,, the product is called aketoxime, or oxime:

oxime of cyclohexanone

Oximes rearrange when heated with a strong acid, and this reaction pro-vides a useful synthesis of amides:

C'H,oxime of 2-propanone N-methylethanamide

This intriguing reaction is known as the Beckmann rearrangement. It has beenthe subject of a number of mechanistic studies that have shown the acid oracid halide (PCI,, C,H,SO,CI) makes the hydroxyl group on nitrogen into abetter leaving group by forming -OH2@ or ester intermediates:

Thereafter, a rearrangement occurs resembling the reactions of carbocations(Sections 8-9B and 15-5E). When the cleavage of the N-0 bond occurs, thenitrogen atom would be left with only six valence electrons. However, as thebond breaks, a substituent R on the neighboring carbon moves with its bonding


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24-36: The Beckmann Rearrangement of Oximeselectron pair to the developing positive nitrogen (Equation 24-5):

Oximes with R and R ' as different gro ups exis t as E and Z isomers (Sect ion19-7 ) an d yo u will no tice in Eq ua tio n 24-5 th at th e grou_~~,-t)at@gr&es is th eo n e t h at is trans to the l eav ing group . T o some e x te n t t he Beckmann rear range----me nt is anYZer%al S,2 reactio n with inv ersion at the nitrogen. Sectio n 2 1- 1 0 Fgives a theoretical trea tm ent of this kind of reaction. T h e rearrangem ent prod -uct is a nitril ium ion, as in the Ritter reaction (Section 24-3B), which addswater to form the amide.T h e synthesis of aza-2-cycloheptanone (E-caprolactam) by th e Beck-mann rearrangement of the oxime of cyclohexanone is of commercial impor-tance because the lactam is an intermediate in the synthesis of a type of nylon(a polyam ide called "nylon-6"":

'The number 6 specif ies the number of carbons in each monomer unit comprisingthe polyamide s t ructure . By th is cod e, nylon-6 ,6 i s (-NH (CH,),NHCO(CH2)4CQ-1 ,,.


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"182 24 Organonitrogen Com pounds I I. Amides, Ni tr iles, Ni tro Compounds

Exercise 24-10 Complete the following reactions to show the structures of the prod-ucts formed :

b. D O H,NOH --+ H2SO4eat ,

24-4 HYDROLYSIS OF AMIDESGenerally, amides can be hydrolyzed in either acidic or basic solution. Themechanisms are much like those of ester hydrolysis (Section 18-7A), but thereactions are very much slower, a property of great biological importance(which we will discuss later):

/PR-C + H 2 0 H@ or @OH /P\ > R - C + R 2 N H\As we have indicated in Section 23-12, amide hydrolysis can be an importantroute to amines. Hydrolysis under acidic conditions requires strong acids suchas sulfuric or hydrochloric, and temperatures of about 100" for several hours.The mechanism involves protonation of the amide on oxygen followed byattack of water on the carbonyl carbon. The tetrahedral intermediate formeddissociates ultimately to the carboxylic acid and the ammonium salt:

O H O H4' H,O 1 0R-C - -C,O - R-C-OH,\ Y\\ INR2 NR2 :N R ,O H O H

0 4'R-C I+ H2 NR2 R-C ,O + H N R , fl=s R-C-OH\ \\O H O H 0 I2H N R ,


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24-4 Hydrolysis of Amides 1183In alkaline hydrolysis the amide is heated with boiling aqueous sodium

or potassium hydroxide. The nucleophilic hydroxide ion adds to the carbonylcarbon to form a tetrahedral intermediate, which, with the help of the aqueoussolvent, expels the nitrogen as the free amine:

Biological amide hydrolysis, as in the hydrolysis of peptides and pro-teins, is catalyzed by the proteolytic enzymes. These reactions will be dis-cussed in Chapter 25.An indirect method of hydrolyzing some amides utilizes nitrous acid.Primary amides are converted easily to carboxylic acids by treatment withnitrous acid. These reactions are very similar to that which occurs between aprimary amine and nitrous acid (Section 23-10):

//R-C //+ HONO -+ R-C + NZ+ HzO\ \Secondary amides give N-nitroso compounds with nitrous acid, whereas

tertiary amides do not react:

A brief summary of important amide reactions follows:reduction, R1CH2NR2hydrolysis/;- R1C02H+HNR,

2 rearrangementR ' C , ( R = H) ) R'NH2 + C 0 2\ dehydration RlcN +H20

( R = H ) >

(Section 18-7C)(Section 24-4)

(Section 23- 12E)

(Section 24-5)\ nitrosation ,R fC 0 2 H r R'CON-N=O (Section 24-4)IR


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1184 24 Organonitrogen Compounds II. Amides, Nitr iles, Nitro CompoundsOf the many other types of organonitrogen compounds known, the more

important includenitriles, R-C-Nisonitriles, R-N=C:

(Section 24-5)

nitro compounds, R-NO, (Section 24-6)nitroso compounds, R-NO (Section 24-6C)

nitrile oxides, R-C--N-0 (section 23; 1 1B)0 0 f-amine oxides, R,N-Q Jisocyanates, R-N=C=O (Section 23- 12E)hydrazines, R,N -NR, (Section 24-7A)azo compounds, R-N=N-R (Sections 23-10C and 24-7B)

0 0diazo compounds, R,C=N=N (Section 24-7C)0 0azides, R-N=N=N (Section 23-12E, Table 23-6, and

Section 24-7D)0diazonium ions, R-N EN (Section 23- 10)00

azoxy compounds, R:~=N-R (Section 24-6C)Although it is impractical to discuss all of these compounds in detail, we nowwill describe briefly several that have not been given much attention heretofore.

The carbon-nitrogen triple bond differs considerably from the carbon-carbontriple bond by being stronger (212 kcal mole-l vs. 200 kcal moleF1)and muchmore polar. The degree of polarity of the carbon-nitrogen triple bond is indi-cated by the high dipole moment (4.0 D) of the simple nitriles (RCN), which ,corresponds to about 70% of the dipole moment expected if one of the bondsof the triple bond were fully ionic. With this knowledge it is not surprisingthat liquid nitriles have rather high dielectric constants compared to mostorganic liquids and are reasonably soluble in water. Ethanenitrile, CH,CN, isin fact a good solvent for both polar and nonpolar solutes (Table 8-5).

Nitriles absorb with variable strength in the infrared in the region2000 cm-l to 2300 cm-l, due to stretching vibrations of the carbon-nitrogentriple bond.

The preparation of nitriles by S,2 reactions between alkyl halides andcyanide ion has been mentioned previously (Section 8-7F) and this is the


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24-5 Nitriles 1385method of choice when the halide is available and reacts satisfactorily. Acti-vated aryl or azaary; halides similarly give nitriles with cyanide ion:

2-chloroaza benzen e 2-cyanoazabenzene, 74%(2-chloropyr idine) (2-cyanopyr id ne)

Another practical route to arenecarbonitriles involves the replacement of the0diazonium group, -N=N, in arenediazonium ions with cuprous cyanide

(Section 23- 1OB). Other useful syntheses involve cyanohydrin formation(Section 16-4A) and Michael addition to conjugated alkenones (Section17-5B).

Nitriles also can be obtained by the dehydration of the correspondingamide or aldoxime. This is a widely used synthetic method and numerousdehydrating agents have been found to be effective:

//CH,CM,-C "05 , H,CH,CrN\ -H20 propa nen itr ile, 55-70%NH2

//CH3-C (C6H5)3P~ C2H5)3N > CH,C--N\ -H,OH ethanenitr i le, 86%The reactions of nitriles include reduction to amines and hydrolysis to

acids. Both reactions have been discussed previously (Sections 18-7C and18-7A).Hydrogens on the alpha carbons of nitriles are about as acidic as thehydrogens alpha to carbonyl groups; accordingly, it is possible to alkylate thea positions of nitriles through successive treatments with a strong base andwith an alkyl halide as in the following example:

1. NaNH,, NH, (1), -80"2. CH,Br

1. NaNH,, NH , (I ), -80"2. CH,Br


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4186 24 Organonitrogen Compounds II. Amides, Nitr i les, Nitro Compounds

Exercise 24-11 Nitri les of the type RCH,CN unde rgo a self-addition reaction analo-gous to the aldol addition in the presence of strong bases such as l i thium amide.Hydrolysis of the init ial reaction product with di lute acid yields a cyanoketone,

0 CNII IRCH,-C-CH-R. Show the steps that are invo lved in the mech anis m of the overallreaction and outline a schem e for its use to synthesize large -ring ketones of the type(CH,),C=O from dini tr ile s of the type NC(CH,),CN.Exercise 24-12 Show how the following substances can be synthesized from theindicate d starting materials:a. (CH,),CCN from (CH,),CCI (two ways)b. CH,CH=CHCN from CH,=CHCH,Brc. CH,=CHCO,H from CH,CHOExercise 24-13 Pro pan edin itrile [malon on itrile, CH,(CN),] reacts with tetracyano -ethene in the pre sen ce of base to yie ld a com pound of formu la HC,(CN),, wh ich is amo noba sic ac id of strength similar to s ulfuric ac id. What is the structure of this com-pound and why is it such a strong acid? Write a mechanism for the formation of thecompound that is based in part on the Michael addition (Section 17-5B).

24-6 NITRO COMPOUNDS24-6A Physical and Sp ectroscop ic Propert iesN itro com poun ds are a very important class of nitrogen derivatives. T h e nitrogroup, -NO,, l ike the carboxylate anion, is a hybrid of two equivalent reso-nance s t ructures :

A

0@/R - N + + R -'oT h e hybrid structure h as a full posit ive charge on nitrogen an d a half-negative charge on ea ch oxygen. This is in accord with the high dipole mom entsof nitro co mp ound s, which fall betw een 3.5 D and 4.0 D, depending upon thenature of R. T h e polar chara cter of the nitro group results in lower volati li tyof nitro com poun ds than k etones of abou t the sam e molecular weight; thus the


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24-68 Preparation of Nitro Com poun dsboiling point of nitrom ethan e (M W 6 1) is 10 1",wh ereas 2-propan one (h1W 58)ha s a boiling po int of 56". Surprisingly, the w ater Solubility is low ; a saturate dsolution of nitrom ethan e in water is less than 10% by w eight, wh ereas 2-propano ne is com pletely miscible with water.

Nitro groups of nitroalkanes can be identified by strong infrared bandsat about 1550 cm-l and 1375 cm-I, whereas the corresponding bands in thespectra of aromatic nitro compounds occur at slightly lower frequencies. Aweak n --+ T * transition occurs in the electronic spectra of nitroalkanes ataround 270 nm; aromatic nitro compounds, such as nitrobenzene, have ex-tended conjugation and abso rb at longer wavelengths (- 330 nm).

24-6B Preparation of N itro CompoundsNitro compounds can be prepared in a number of ways, including the directsubstitution of hydrocarbons with nitric acid,

by displacement reactions with nitrite ions,

and by o xidation of primary amines,

Nitration of alkanes is successful only when con duc ted at high temper atures inthe vap or ph ase. M ixtures of products are invariably obtained (Section 4-6):

In contrast , direct nitrat ion of aromatic compounds such as benzene takesplace readily in th e liquid p hase , as discussed in Section 2 2-4C.Like o the r electrophilic su bstitution s, nitration of a substituted benzene,where the subs ti tuent is e lect ron wi thdrawing (NO , , C 0 2 H , C N , and so on;Table 22-6), generally p roduces th e 1,3-isomer. To prepare the 1,4-isomer,less direct routes are nece ssary -the usual strategem being to use benzenederivatives with substituent groups that produce the desired orientation on


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24 Organo nitrogen Com pounds I I. Amides, Nitr i les, Nitro Compo undsNHCOCH, NHCOCH,

HNO,CH,CO,Na H.SO 0" '

benzenamine(anil ine) N-phenylethanamide(acetani l de)NO,

N-(4-nitropheny1)-ethanamide(para-ni troacetani l ide)

Q NaN5u1 Q ./;;O;O QNO2 NO2 NO21,4-dini trobenzene 4-ni trobenzenamine(para-nitroanil ne)

CF,CO,H3HCI, (90%) I ,H,OH,NH3 100"NO,

chlorobenzene 1 chloro-4-ni trobenzeneFigure 24-5 Synthetic routes to l ,4-dini trob enze ne

nitration and then to make the necessary modifications in these groups toproduce the final product. Thus 1,4-dinitrobenzene cannot be obtained bynitration of nitrobenzene but can be prepared from benzenamine by thesequence shown in Figure 24-5. Benzenamine is converted to N-phenyl-ethanamide (acetanilide) which on nitration yields the l,4-isomer. Hydroly-sis of the amide to 4-nitrobenzenamine and replacement of amino by nitro,using nitrite ion in the presence of cuprous salts, gives 1,4-dinitrobenzene (seeSection 23- IOB). Alternatively, the amino group of 4-nitrobenzenamine can beoxidized to a nitro group by trifluoroperoxyacetic acid. In these syntheses,N-phenylethanamide is nitrated in preference to benzenamine itself because,not only is benzenamine easily oxidized by nitric acid, but the nitration


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24-66 Preparation of Nitro Compounds 4189reaction leads to extensive 3-substitution as the result of formation of phenyl-ammonium ion. Another route to 4-nitrobenzenamine is to nitrate chloro-benzene and subsequently replace the chlorine by reaction with ammonia. Thenitrations mentioned give mixtures of 2- and 4-isomers, but these usually areeasy to separate by distillation or crystallization. The same approach can beused to synthesize 4-nitrobenzoic acid. The methyl group of methylbenzenedirects nitration preferentially to the 4 position, and subsequent oxidation withchromic acid yields 4-nitrobenzoic acid:

NO,

In some cases it may be necessary to have an activating group to facilitatesubstitution, which otherwise would be very difficult. The preparation of1,3,5-trinitrobenzene provides a good example; direct substitution of 1,3-dinitrobenzene requires long heating with nitric acid in fuming sulfuric acid.However, methylbenzene is converted more readily to the trinitro derivativeand this substance, on oxidation and decarboxylation (Section 18-4), yields1,3,5-trinitrobenzene:

NO,65%

Acylamino groups also are useful activating groups and have the advantagethat the amino groups obtained after hydrolysis of the acyl function can beremoved from an aromatic ring by reduction of the corresponding diazoniumsalt with hypophosphorous acid, preferably in the presence of copper(1) ions.


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24 Organonitrogen Compounds II. Amides, Nitriles, Nitro CompoundsA n example is the preparation o f I -methyl-3-nit robenzene f ro m N -(4-me thyl-pheny1)ethanamide (aceto-para-toluidide):

H N 0 3 > p aOH,/ \ HCl, 0"NO, ' O,NH NHI I NH2C=O c=oI ICH3 CH3N-(4-methylpheny1)ethanamide(aceto-para-toluidide)

Exercise 24-14 Show how the fol lowing compounds may be synthesized from theind ica ted starting m aterials. (It may b e necess ary to review parts of Chap ters 22 and23 to work this exercise.)a. 1-methyl-3,5-dinitrobenzene from methyl benzen eb. 1 methyl-2,6-dinitrobenzene from 4-methyl benzen esulfonic ac id (notice that-SO,H can be remov ed by hyd rolys is; Section 22 -46 )c. 2,4-dinitrobenzenamine from chlorobenzened. 1-chloro-33-dinitrobenzene from chlorobenzenee. 1,2,3-trinitrobenzene from 4-chlorobenzen esulfonic ac id

Routes to aliphatic nitro compounds include the reaction of an alkylhalide (of goo d S,2 reactivity) with nitrite ion. Suitab le solve nts are me thyl-sulfinylmethane [dimethyl sulfoxide, (CH ,),SO] and dimethylmethanam ide(dimethylformamide). As will be seen from Equation 24-6, formation of thenitri te este r by 0 - instead of N-alkylation is a competing reaction:CH,(CH,) ,Br + N a N O , H C O N ( CH 3 )2-NaBr


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24-6C Reactions of Nitro CompoundsSilver nitrite sometimes is used in preference to sodium nitrite, usually indiethyl ether as solvent:

ICH2C02C2H5 AgNO,0, ther

> 02NCH2C0,C2H5+ AgIethyl nitroethanoate77%Nitromethane can be prepared conveniently by the reaction

heat -CO,ClCH2C02H+NaNO, -NaC1 > [02NCH2C02H] heat > 0,NCH3Displacement reactions with nitrite ion do not work well with aryl

halides. However, displacement of the diazonium group is a practical route tonitroarenes (the Sandmeyer reaction), as described in Section 23-10B:HONO @ArNH, ArN, CuNo2 > ArNO,

24-6C Reactions of Nitro Com pound sNitro compounds are quite unstable in the thermodynamic sense; for example,the heat of decomposition of nitromethane, according to the following stoichi-ometry, is 67.4 kcal molew1.CH3N02 --+ &N2+ CO, + $He AH0= -67.4 kcal mole-]Advantage is taken of the considerable energies and rapid rates of reactionssuch as this in the commercial use of nitro compounds as explosives. Withsome nitro compounds, such as TNT, there is a further advantage of low shocksensitivity.

I-methyl-2,4,6-trinitrobenzene(2,4,6-trinitrotoluene, TNT)TNT is not detonated easily by simple impact and even burns without explod-ing. However, once detonation starts, decomposition is propagated rapidly.The characteristics of reasonable handling stability and high thermodynamic


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24 Organonitrogen Compounds I I . Amides, Nitriles, Nitro Compoundspotential make nitro compounds particularly useful. Other polynitro com-pounds that are useful as explosives include PETN (Section 17-3C), cyclonite(Section 16-4C), picric acid, and tetryl:

NO2 NO,2,4,6-trinitrobenzenol N-methyl-N-nitro-2,4,6-(picric acid) trinitrobenzenamine(tetryl)

An important characteristic of aromatic polynitro compounds is their ability toform "charge-transfer" complexes with aromatic hydrocarbons, especiallythose that are substituted with alkyl groups. Complexes of 2,4,6-trinitro-benzenol (picric acid) and aromatic hydrocarbons often are crystalline solids,which are useful for the separation, purification, and identification of aromatichydrocarbons. These substances are called "hydrocarbon picrates," but thename is misleading because they are not actually salts. Furthermore, similarcomplexes are formed between aromatic hydrocarbons and trinitrobenzene,which demonstrates that the nitro groups rather than the hydroxyl group areessential to complex formation. The binding in these complexes resemblesthat in the rr complexes of halogens with alkenes and benzene (Sections 22-4Dand 10-3C) and results from attractive forces between electron-rich andelectron-poor substances. The descriptive name-charge-transfer complex-suggests that the complex has VB structures involving transfer of an electronfrom the donor (electron-rich) molecule to the acceptor (electron-poor) mole-cule. The name n complex also is used because, usually at least, one componentof the complex has a T-electron system. Charge-transfer or n complexesbetween polynitro compounds and aromatic hydrocarbons appear to givesandwich-type structures with the aromatic rings in parallel planes, althoughnot necessarily centered exactly over one another:

7 TI electronsNO, NO2

t--j

formulation of charge-transfer complex between 1,3,5-trinitrobenzene(acceptor) and 1,3,5-trimethyl benzene (donor)

Charge-transfer complexes are almost always more highly colored than theirindividual components. A spectacular example is benzene and tetracyano-


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24-66 Reactions of Nitro Compoundsethene, each of which separately is colorless, but which give a bright-orangecomplex when mixed. A shift toward longer wavelengths of absorption, relativeto their components, is to be expected for charge-transfer complexes becauseof the enhanced possibility for stabilization of the excited state through electrondelocalization involving both components.

Exercise 24-15 Tetracyanoethene in benzene forms an orange solution, but whenthis solution is mixed with a solution of anthracene in benzene, a bril l iant blue-gree ncolor is produ ced , which fades rapidly ; colorless crystals of a compo und of compos i-tio n C,,H,,.C,(CN), then are de po si ted. Exp la in the co lor ch an ge s that oc cu r and wr itea structure for the crystalline product.Exercise 24-16 Would you expect the dipole moment measured for 1,3,5-trinitro-benzene in 1,3,5-trimethylbenzene solution to be the same as in tetrachloromethanesolut ion? Explain.Exercise 24-17 Anthracene (mp 217") forms a red crystal l ine complex (mp 164")with 1,3,5-trinitrobenzene (mp 121 ). If you were to purify anthracene as this com plex,how co uld you regenerate the anthracene free of trinitrobenzene?

Reduction of nitro compounds occurs readily with a variety of reducingagents and such reductions afford a particularly useful synthesis of aromaticamines (Section 23- 12B):

NO2 NH ,I Sn. HC1, 50-100" 1/El,, ki, 2i0, 30 atm

The reduction of a nitro compound to an amine requires six equivalents ofreducing agent:R-NO, + 6H@ + 6e0 --+RNH, + 2H20One would not expect such a reduction to occur in a single step. Indeed,reduction is stepwise and proceeds through a string of intermediates, which.with strong reducing agents in acid solution, have at most a transient existence.The intermediates formed successively from RNO, by increments of twoequivalents of reducing agent are nitroso compounds, R-N=O, and N-substituted azanols (hydroxylamines), RNHOH:

2[H1 > RN=ORNo, -H,O 2[H1 > RNHOH -H,OrH1 > RNH,


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1194 24 Organonitrogen Com pounds II . Amides, Nitr i les, Nitro CompoundsThus N-aryl-substituted azanols can be obtained directly from the corre-sponding nitro compounds with zinc and ammonium chloride solution. How-ever, zinc and hydrochloric acid gives the amine:

The difference between these reactions is in the reduction rates associatedwith the acidity of the solution. Ammonium chloride is a much weaker acidthan HC1; the pH of ammonium chloride solutions is around 6.Oxidation of the N-arylazanols under controlled conditions yieldsnitroso compounds. This reaction is not unlike the oxidation of alcohols toketones (Section 15-6B):

Reduction of aryl nitro compounds with less-powerful reducing agents, espe-cially in alkaline media, gives what may appear to be a mysterious conglomerateof bimolecular reduction products. For example, with nitrobenzene,

-0I / \ 1.2-diphenyldiarene oxide(azoxybenzene)-

/ I z ~ , aOH2 0 h 0 2 Zn78 equiv)aOH > ~ ~ yiphenyldiazeneazobenzene)

Zn, NaOH

(10 equiv) (hydrazobenzene)

All of these substances can be reduced to benzenamine with tin and hydro-chloric acid. As a result, each could be, but not necessarily is, an intermediatein the reduction of nitro compounds to amines. Formation of the bimolecularreduction products is the result of base-induced reactions between nitrosocompounds and azanols or amines and possibly further reduction of the initiallyproduced substances (see Exercise 24- 18).


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24-6C Reactions of Nitro Compounds 1195

Exercise 24-18" Write the mec hanistic steps to show how 1,2-diphen yldiazen e oxideand 1,2-diphenyldiazene may b e formed by base-induced c ondensation reactions ofnitrosobenzene with N-ph enylaz anol and benzenamine, respec tively. What productwould you expect to be formed from nitrosobenzene and N-(4-chlorophenyl)azanol?Give your reasoning.

Several polynitrobenzene derivatives have important herbicidal uses. Examplesare N3,N3-diethyl-6-trifluoromethy1-2,4-dinitro-3-benzenediamine and N ,N-dipropyl-4-trifluoromethyl-2,6-dinitrobenzenamine:

cF~ CF3N3 ,N3-diethyl-6-trifluoromethyl- N,N-dipropyl-4-trifluoromethyl-2,4-dinitro-1,3-benzenediamine 2,6-dinitrobenzenamine(dinitramine) (trifluralin)

These substances when mixed with soil kill weed seedlings but not crop plantssuch as cotton, soybeans, and peanuts. The activity is high; normally onlyabout 0.08 g metere2 is required for good weed control.The most important react ions of nitroalkanes are those involving the

a hydrogens of the primary and secondary compounds. For example, n i tro-methan e is sufficiently acidic to dissolve in aque ous hydroxide solutions. T h eanion so produ ced has an electronic structure analogous to the ni trate anion:

A n interesting property of this ion is th at whe n solutions of it ar e acidified, anunstable, ra ther strongly acidic isome r of nitromethane (called the aci form) isproduced, which slowly reverts to the more stable nitro form:OW

H@ @/ slow~ ~ 2 ~ 0 2 ~-+ C H 2 = N s ---+ CH,NO,ac i form


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1?I96 24 Organonitrogen Com pounds I I . Amides, N itr iles, Nitro Compound sSimilar changes take place in the acidification of the en01 salt of a carbonylcompound, the principal difference being the much longer l ife of the aci-nitrocom pound com pared to that of an enol of a s imple ketone (see Sect ion 17- 1B).Primary and secondary ni t ro compounds undergo aldol addi t ions andMichael addi t ions with sui table carbonyl com pound s and basic catalysts:

Unfortunately , alkylat ion react ions analogous to the base-catalyzedalkylation of carbon yl com pou nds general ly are not useful for the sy nthesis ofhigher ni tro c om pou nds , becau se C-alkylat ion of the conjugate bases ofpr imary n i t ro compo unds i s s lower than 0-a lky la t ion .

Exercise 24-19 What kin d of prop ert ies and react ions wou ld you exp ect the doublebond of nitroethene to have? Consider the ease of electrophil ic and nucleophil icaddit ion reactions as well as cycloaddit ions.Exercise 24-20 Show how the fol lowing com pound s can be prepared from the com-mercially available nitroalkanes obtained from the nitration of propane. (It may bedesirable to review the material on aldol and Michael addit ions in Chapters 17and 18.)a. HOCH,CH,NO, d. HOCH,C(CH,),NH,b. CH,=CHNO, e. (N-CCH,CH,),CNO,c. (O,NOCH,),CNO, 8 . H,NCH,CH,C(CH,),NH,Exercise 24-21 Show how 2-methyl-2-nitropropane may be synthesized from (a)tert-butyl alcoh ol and (b) 2,2-dimethylpropa noic ac id. (Review Sections 23-12E and24-3B if necessary.)


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24-7A Hydrazines24-7 SOME COMPOUNDS WITH N-N BONDSAmong the organic nitrogen compounds having nitrogen above the oxidationlevel of ammonia are a wide variety of substances with N-N bonds. We shallmention only a very few of the more important of these substances: hydrazines,azo and diazo compounds, and azides.

24-7A HydrazinesOrganic hydrazines or diazanes are substitution products of NH,-NH, andhave many properties similar to those of amines in being basic and formingacyl derivatives as well as undergoing alkylation and condensations withcarbonyl compounds (Section 16-4C). Unsymmetrical hydrazines can beprepared by careful reduction of N-nitrosamines. 1 l Dimethyldiazane isprepared in this way for use as a rocket fuel:

Aromatic hydrazines are best prepared by reduction of aromatic diazoniumsalts (Table 23-4).H HI IHydrazines of the type R-N-N-R are easily oxidized to the corre-

sponding azo compounds, R-N=N-R. With nitrous acid, monosubstitutedhydrazines are converted to azides:

HI 0 0R-N-NN, + HONO --+ R-N=N=N + 2 H 2 0Exercise 24-22 Arguing on the basis of mechanist ic principles and knowledge ofrelated reactions, work out produ cts that may be exp ec ted for the follow ing reactions:

CH3 CH, CH,la. CH,-N-NH, + HONO I IC. CH3-N-N-CH3 + HONO

C H H 0I I I Ib. CH,-N-N-CH, + HONO d. CH,-C-NH-NH, + Br2+ NaOH


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4 198 24 Organoni t rogen Com pounds I I . Amides , Ni t r iles, Ni t ro Compou nds24-7B Azo CompoundsAzo or diazene compounds possess the - - N = N - grouping. Aliphatic azocompounds of the type R-N=N-H appear to be highly unstable anddecompose to R-H and nitrogen. Derivatives of the type R-N=N-Rare much more stable and can be prepared as mentioned above by oxidationof the corresponding hydrazines. Aromatic azo compounds are available inconsiderable profusion from diazo coupling reactions (Section 23-10C) andare of commercial importance as dyes and coloring materials.

A prime characteristic of azo compounds is their tendency to decom-pose into organic free radicals and liberate nitrogen:

The ease of these reactions is usually a fairly reliable guide to the stabilitiesof the free radicals that result. For instance, it is found that dimethyldiazene(azomethane, CH3N=NCH3) is stable to about 400, and diphenyldiazene(azobenzene, C6M,N=NC6H,) also is resistant to thermal decomposition;but, when the azo compound decomposes to radicals that have extra stabilitybecause of delocalization of the odd electron, the decomposition temperatureis greatly reduced. Thus the azo compound, 2, decomposes to radicals atmoderate temperatures (60" to 100), and for this reason is a very useful agentfor generating radicals, such as those required for the initiation of polymeriza-tion of ethenyl compounds:

Exercise 24-23 Arrange the fol lowing azo substances in order of their expectedrates of thermal d ecom posit ion to pro du ce nitrogen. Give your reasoning.


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24-7C Diazo Com poundsExercise 24-24 Devise a synthesis (more than one step m ay be required) of 2 from2-propanone, hydrazine, and hydrogen cyanide. What would you expect this sub-stance to yie ld when heated in (a) a perf luorohydro carbon solvent and (b) a solutionof brom ine in carbon tetrachloride?

24-76 Diazo Compounds0 0T he parent of the diazo compounds, diazomethane, C H 2 = N = N , has beenmentioned before in connection with ylide reactions for ring enlargement(Section 16-4A) and the preparation of methyl esters from acids (Table 18-7).

I t is one of the m ost versatile and useful reagents in organic chemistry, despitethe fact that it is highly toxic, dangerously explosive, and cannot be storedwithout decom position.Diazomethane is an intensely yellow gas, bp -23", which customarilyis prepared and used in diethyl ether or dichloromethane solution. It can besynthesized in a nu m ber of ways, the most useful of which em ploys the actionof base on a n N-nitroso-N-methylamide:

/PR-C @ ether 0+ O H R - C 0 2 + C H 2 N 2 + H 2 0

A s a methylating agent of reasonably acidic substances, diazom ethanehas nearly ideal properties. It can be used in organic solvents; reacts veryrapidly without need for a cata lyst (except with alcoh ols, which do require anacid catalyst); the coproduct is nitrogen which offers no separation problem;it gives essentially quantitative yields; and it acts a s its own indicator to showwhen reaction is complete. With enols, it gives 0-alkylation:

O C H , 0I I / I I ICH,-C\ ,C-CH3 + C H 2 N 2---) CH,-C\CkC-CH:, f N 2C HR-C-OH + C H 2 N 2 --+ R-C-OCH3 + N 2


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24 Organonitrogen Compounds I I . Amides, Nitriles, Nitro CompoundsBesides being a methylating agent, diazomethane also is a source of :CH, whenirradiated with light. The carbene formed in this way is highly reactive and evenwill react with the electrons of a carbon-hydrogen bond to "insert" the carbonof the carbene between carbon and hydrogen. This transforms -C-H to-C-CH3:

This :CH, species is one of the most reactive reagents known in organicchemistry.

Diazomethane undergoes a wealth of other unusual reactions. Besides thosealready mentioned are the following two examples:

Arndt-Eistert synthesis (-COCI -+ -CH2C02H, Section 16-4A)

1-naphthalenecarbonyl chloride 2-diazo-1 (1-naphthyI)ethanone92%

COCHN, CH=C=O

Pyrazoline forma tion ( [2 + 31 cycloaddition)

The Arndt-Eistert synthesis is useful for converting an acid to the next highermember of the series. Pyrazolines are important intermediates for the prepara-tion of cyclopropanes:

CH, / C H 3/ heat Cq CH 3CH . 7 \ C 0 2 ~ ~ 3----t I ,C\ + N2\ N , ~ ~ CH, CO2CH3


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24 Organoni t rogen Compounds II. Amides, Nitr i les, Nitro Compoundssyntheses of these substances are relatively simple. One of several possibleroutes follows:

R a diazacyclopropene

Exercise 24-28* Kn owin g that ke tones and hydrazine react to give hydrazones, showhow the co m bina tion of ketone, NH,, an d NH,CI ca n react to giv e diaz acyclo pro pa nes .In working out a mechanism, start with the fact that the following reaction occurs ingood yie ld:

Exercise 24-29* Explain why 1,2-d azacyclopropen e reacts with ac ids m uch m oreslowly than does diazomethane.

24-7D AzidesOrganic azides can be prepared from hydrazines and nitrous acid (Section24-7A ) and by t he reaction of sodium azide with acyl halides or with alkylhalides having good SN 2 eactivi ty:

The lower-molecular-weight organic azides often are unpredictably explosiveand ar e best handled in solution.The use of acyl azides in the preparat ion of amines by the Curt iusrearrangem ent has been discussed previously (Section 23- 12E). Alkyl azidescan be reduced readily by lithium aluminum hydride to amines and, if a pureprimary amine is desired, the sequence halide --+ zide --+ amin e may giveas good or better results than does the Gabriel synthesis (Section 23-9D).


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Supplementary Exercises 1283

Exercise 24-30 Show how the fol lowing transformations may be achieved w ith theaid of azide derivatives:

Additional Reading

I. T. Mi l ler and H. D. Springal l , Sidgw ick's Orga nic Chemistry of Nitrogen, 3rd ed., TheClarend on Press, Oxford, 1966.L. G. Donaruma and W. Z. Heldt, "The B eckm ann Rearrangement," Organic Reactions11, I (1960).

Supplementary Exercises

24-3 1 Sugg est a route for the synthesis of eac h of the follow ing c om pou nds from theindicated start ing material :a. 2-me thylpropane nitr ile from 2-methylpropanalb. (CH,CO,CH,),C-NO, from nitro methanec. N-tert-butyl benze necarb oxam ide from benze necarb onitr i le (be nzonitr i le)24-32 a. Make a chart of the m p, bp, and solubi l i ties in water, ether, di lute ac id, anddi lute base of each of the fol lowing compounds:octanamine NJN-dimethylethanamideN-buty l butanamine NJN-dipropylpropanam ine1 ni trobutane 2-ni tro-2-methyl butaneb. Outl ine a p ractic al proce dure for separation of an equimo lal m ixture of each of thecompounds in Part a into the pure components. Notice that selective reactions arenot suitable unless the reaction product can be reconverted to the starting material.Fractional dist i llat ion wi l l not be a cce pted here as a pra ctical means of separation ofcompounds that have boi l ing points less than 25" apart.

24-33 For each of the fol lowing pairs of com poun ds g ive a chem ical test, preferablya test-tube re action, that wi l l dist inguish between the two com poun ds:a. (CH,),CNH, and (CH,),NC,H,b. CH,CH,NO, and CH,CONH,


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1204 24 Organonitrogen Compounds II. Amides, Nitr i les, Nitro Compoundsc. CH3CH2C=N and HC=C-CH2NH2

0 0d. CH3CH2NHCIand CH3CH2NH3CIe. CH,NHCOCH3 and CH 3N HC 02C H3f. CH30CH2CH2NH2 nd CH3NHCH2CH20Hg. CH3CH2CONH2 nd CH30CH2C H2NH2

24-34 Exp lain how you would use spectroscop ic means to dist inguish between thecompound pairs in Exercise 24-33. Be specif ic about what you would expect toobserve.24-35 Using s pectrosc opic me thods, how co uld you dist inguish one isomer from theother in the fol lowing pairs? Be specif ic about what you would expect to observe ineach case.a. 2-methyl benzenamine and N-methyl benzenamineb. propanamide and N,N-dimethylmethanamidec. nitroethane and ethyl nitrited. 3-oxobutaneni tr i le and 2-butynamide24-36 Com pound A of molecular formula C6H12 N202which can be obtained resolvedinto chiral forms) is insolub le in di lute ac id and d i lute base, but reacts with aqueousni t rous acid to give compound B of form ula C6Hl,04, wh ich re ad ily lose s water onheating to giv e C, C,H,03. Co m pou nd A reacts with a solution of brom ine and so diumhydroxide in water to give D, C4H,,N2, which on treatment with nitrous acid in thepresen ce of perchloric a cid give s 2-butanone. Write structures showing con figurat ionsfor compounds A, 5, C, and D and equations for al l the react ions involved.24-39 How wou ld you synthesize the fol lowing com poun ds from the indic ated start ingmaterials? Write equations for the react ions involved and indicate the react ioncondit ions.a. phenyl nitroethanoic ac id from ethyl phenylethanoateb. 3-phenylpropanoic acid f rom phenylethanoic ac id24-38 Show by equations how each of the fol lowing substances m ight be synthesizedfrom the indicated materials. Specify reagents and approximate react ion condit ions.Assume that any isomers formed are separable.a. N-phenylethanamide from benzeneb. 1,2-dinitrobenzene from N-ph enylethan am idec. 4-nitro-1 -nitrosobenzene from N-ph enylethan am ided. 1,3,5-tr ideuteriobenzen e from N-ph enylethan am idee. 2,4-dinitrophenyldiazane (2,4-dinitrophenylhydrazine) from benzene24-39 For each of the fol lowing pairs of compo unds give a chem ical test, preferablya test-tube reaction, that will dist inguish the two compounds. Write a structuralformula for each com poun d a nd eq uations for the react ions involved.a. Ime thyl-3-n itrobenz ene an d pheny lnitrome thane


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Supplementary Exercisesb. 1-methyl-4-nitrobenzene and benzenecarboxamidec. benzenamine and cyclohexanaminedl. N-m ethyl benzenamine and 4-methyl benzenaminee. N-nitroso-N-methyl benzenamine and 4-nitroso-N-methyl benzenamine24-40 Show how the fol lowing substances may be synthesized from benzene, nitro-benzene, and halogen ated or alkylbenzenes, u sing the reactions discusse d i n thischapter and in Chapters 22 and 23.a. 3-n tro benzenamineb. 1-bromo -4-n itrosobenzenec. 2-methyl-5-nitrobenzenamined. 1-(4-bromopheny1)-2-(4-chlorophenyl)diazanee. phenyl-(4-nitropheny1)diazenef. 1-phenyl-2-(4-methylpheny1)diazene 1-oxide

bpo c chapter 24

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