Acidities of some cyano compounds

Second-row elements, particularly phosphorus and sulfur, are known to stabilize adjacent carbanions. The pA s of some pertinent compounds are given in Table 7.6. 

The conjugate base of 1,3-dithiane has proven very valuable in synthetic applications as a nucleophilic carbonyl equivalent (Part B, Chapter 10), and is quantitatively generated by metalation with n-butyllithium  

The pK of 1,3-dithiane has been determined to be 31 (in cyclohexylamine). Analysis of substituent effects, as well as ab initio SCF-MO calculations, have led to 

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The behaviour just discussed applies to the reactions of several classes of carbon acids, notably the removal of a proton from nitro- and keto-compounds, and the addition of a proton to aromatic systems. In all of these systems there is good evidence that the reaction is accompanied by a drastic electronic rearrangement, and it is of interest to enquire why some other classes of carbon acids, notably the cyano-compounds and the disulphones, behave quite differently. Some of these compounds are strong enough acids for their dissociation constants to be measurable in aqueous... 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

IH- 1,2,4-Benzotriazepines can be prepared in good yield by the reaction of some hydrazidoyl chlorides of type (461) with cyano compounds. The reaction is thought to proceed via the nitrilium salt (462). The products (463) are stable to alkali but are hydrolyzed in acid to give 1-phenyl-3R-indazoles (74T195). 

Some reports describe the nucleophilic attack at the cyano carbon atom of DECP without P-CN bond splitting. For example, the cycloaddition of lithium trimethylsUyldiazomethane and nitrile oxides to the cyano group of DECP produces 1,2,3-triazole and l,2,4-oxadiazole-4-phosphonates, respectively. In the presence of a Lewis acid, which increases the electrophilicity of the cyano carbon atom, compounds containing active methylene groups add to the cyano group to give a,P-unsaturated oc-aminophosphonates (Scheme 6.46). ... 

Most activity in this area has centered around the isolation of so-called pseudo-bases (82) in which the cyano group is replaced by a hydroxy group. Thus the pseudo-base is obtained, in addition to the normal Reissert compound, from S-nitroisoquinoline, " 3-methyl-5-nitroisoquinoline, 6-nitroquinoline, and phthalazine. Heating the pseudo-bases in alcohol gives rise to the ethers 83. A discussion of some of the chemistry and properties of the pseudo-bases has appeared. The formation of the pseudo-bases can be suppressed and that of the Reissert compounds increased by the use of a phase-transfer catalyst. Pseudo-bases have also been obtained in attempts to form Reissert compounds from 1,6-naphthyridine and 4,6-phenanthroline. 2-Phenyl-1,2,3-thiadiazole and benzoyl chloride in the presence of cyanide gave 84 and imidazo[l,5-a]pyrazines with acid chloride gave 85 in reactions analogous to the pseudo-base formation. 

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