Alkylation of nitriles

The reductive capability of CgK has been a subject of interest (LA). Uses for CgK include the reductive cleavage of carbon-sulfur bonds (S5), the reductive alkylation of nitriles and esters (S6), and the reductive alkylation of aldehydes and ketones (S7). The activity of CgK has... 

Nitriles (see also Dicyano Compounds, Cyano Carbonyl Compounds, etc.) 10-105 Alkylation of nitriles... 

Hence ketone (1) might be made by regioselective alkylation of (2) but this is doubtful. A safer route is to disconnect the ethyl group to leave nitrile (3) which can certainly be made by alkylation of nitrile (4) as there is only one site for enolisation. 

Alkylation of nitrile (4) needs only moderately strong base (hydroxide will do ) as the benzene ring helps to stabilise the anion (5),... 

Nitrilium salts, e.g., 66, prepared from the alkylation of nitriles, react with sodium azide to yield 1,5-disubstituted tetrazoles, e.g., 67 (Scheme 7).121 The Schmidt reaction,122 a versatile method for the preparation of 1,5-disubstituted tetrazoles from ketones and hydrazoic acid, can now be regarded as a special case of azide addition to nitrilium salts.123... 

Alkylation of nitriles 0-99 Reaction of halo nitriles or diazo nitriles with boranes... 

The alkylation of nitriles has been developed as a general method for the preparation of substituted acetonitriles. An excellent discussion of the literature to 1937 has been given. The procedure consists in treating a nitrile in an inert solvent with finely divided sodium amide and the halogenated compound, followed by careful hydrolysis with water. Common solvents are ether, benzene, toluene, or liquid ammonia. Mono-, di-, and tri-alkylated products are possible, as shown by the alkylation of acetonitrile with ethyl bromide however, the mixtures can often be separated by fractional distillation. 

The N-alkylation of nitriles with aralkyl alcohols, a special case of the Ritter reaction, is a novel general reaction. The following compounds were prepared by this procedure in the corresponding yields N-benzylacetamide (48%), N-(2,4-di-methylbenzyl)-acctamide (40%), N-(4-methoxybenzyI)-acetam-ide (60%), N,N -diacrylyl-/> Xylene-a-o -diamine (64%), N,N -diacetyl-4,6-dimethyl-jM-xyleue-a, -diamine (62%). 

Cacace, F., Ciranni, G., Giacomello, P. Alkylation of nitriles with gaseous carbenium ions. The Ritter reaction in the dilute gas state. J. Am. 

Intramolecular alkylations of nitrile-stabilized carbanions have been used to synthesize large rings such as those with 10 and 14 members. Tsuji and coworkers carried out a synthesis of the macrocy-clic antibiotic zearalenone by this route. As shown in Scheme 70, conversion of either of the protected cyanohydrins (144) or (145) to the corresponding dianions, resulting from deprotonation at the benzylic positions and a to the nitrile groups, gave the same cyclization product (146) in excellent yields. Dianion formation (i) provided control of the conformation of the side chain (ii) protected the ester from nucleophilic attack and (iii) appeared to increase the rate of the intramolecular cyclization. 

It is known that nitrilium salts can be prepared by alkylation of nitriles , via the reaction of imidoyl chlorides with Lewis acids as well as by Beckmann rearrangement of oximes . The application of nitrilium salts in organic synthesis is summarized in a number of reviews " . In this connection it is appropriate to mention another three-component one-pot synthesis of 5,6-dihydro-4. -l,3-oxazines 40 based on the reaction of aldehydes with iV-tcr/-butylnitrilium salt 41 which, however, proceeds without the participation of Af-acyliminium ions . The reaction is carried out by mixing the aliphatic or aromatic aldehyde, tcrt-butyl chloride and Lewis acid (SbCljjSnC ) in benzonitrile solution (equations 16 and 17). 

Compared with these methods, the reductive N-alkylation of nitriles is much more efficient and practical. The starting materials and reagents are cheaper, and only two steps are involved that proceed in a higher overall yield. Reductive N alkylation affords, without any chromatographic separation, a product of high purity. 

SECONDARY AND TERTIARY AMINE SYNTHESES BY REDUCTIVE N-ALKYLATION OF NITRILE... 

USE In Claisen condensations, alkylation of nitriles and ketones, synthesis of ethynyl compds, acetylenic carbinols. 

A serious problem in the alkylation of nitriles is the occurrence of subsequent introduction of a second substituent ... 

Reductive alkylation of nitrile by secondary amines having the same or different alkyl chains is another alternative for tertiary amine preparation. Many other special cationics, N-alkyl monoaza crown ethers [53], for example, can be classified as tertiary amines. The surface-active tertiary amine compounds are used as such (as corrosion inhibitors, dopes, antistatics, reagents in mineral processing) or as semifinished products. Alkyldimethylamines and dialkylmethylamines were run on a commercial level, e.g., by Albemarle (former Ethyl Corp.) as ADMA Tertiary Amines and DAMA Tertiary Amines , respectively. 

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