Amidine formation nitrile addition

The reactivity of coordinated nitriles towards nucleophiles, and electrophiles when deprotonated, has been of major interest. Addition of OH- to the nitrile carbon occurs readily in alkaline solution, kobs = oh[OH-]) and the rate is increased some 106—107 times by coordination (equation 24).176177 k0H has values of 1-50mol-1 dm3 s 1 for R = alkyl177 [e.g. 3.4 (Me) 35 (CH=CH,)j and varies over a wider range for substituted benzonitriles following a Hammett relationship.For 2-cyanoben-zonitrile addition of one equivalent of OH is followed by intramolecular amidine formation on treatment with further alkali (29), or by rearrangement in acid and hydrolysis to the diamide (31), or cyclization to the alternative amidine isomer (32 Scheme 17).179 The alkaline hydrolysis of the... 

The formation of compounds 2-503 proceeds via the addition of a hydrazide 2-500 onto the central carbon of an isothiocyanate 2-499. Subsequent cyclization by attack of the hydrazide nitrogen in the formed 2-501 onto the nitrile moiety gives intermediate 2-502. A further attack of the newly formed amidine nitrogen onto the carbonyl group followed by extrusion of water affords the triazoloquinolines 2-503. 

PINNER REACTION. Formation of imino esters (alkyl imidates) by addition of dry hydrogen chloride to a mixture of a nitrile and an alcohol. Treatment of alkyl imidates with ammonia or primary or secondary amines affords amidines. while treatment with alcohols yields ortho-esters. 

It is well known that the addition of ammonia or amines to nitriles leads to formation of various amidines 32 this type of oligomerization can be applied to the synthesis of heterocycles. On heating in the presence of sodium amide (or benzenesulfonic acid in some cases), o-cyanoaniline produces a mixture of the quinazoline (18) by dimerization and the tricycloquinazoline (19) by trimerization the trimer is obtained when the dimer is heated with another molecule of the monomer and sodium amide at 300°. The mechanism of this condensation has been reviewed.33... 

Dehydrohalogenation of amide chlorides affords a-chloroenamines, which undergo cycloaddition with IV-diphenylmethylaldimines to furnish azetidinium salts (303 equation 161). From these salts the diphe-nylmethyl group can be removed by hydrogenation, subsequent deprotonation yields 2-amino-1-aze-tines. The addition of primary or secondary amines to nitrilium salts gives rise to formation of amidinium salts and amidines respectively, e.g. (304 equation 162). In a similar reaction from copper(I) imidazolide, r-butyl bromide and nitriles amidines (305 equation 163) were prepared. ... 

Nitriles react with amides by initial deprotonation at the a position or by addition of NH2 and formation of amidine salts. The extent of each reaction channel depends on the reaction conditions, the acidity of the nitrile, and the existence of fast, secondary reactions [1,2]. 

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