Amine reaction with nitriles

Polymers derived from the preceding type of reaction with nitriles,5 amines,6 and phosphines,7 have been reported. Green8 has reported the preparation of a resin-type material composed of at least 10 repeat units from the reaction between decaborane and adiponitrile (NC(CH2)4CN). Also reported,9 is the inclusion of flexible siloxanes and ether linkages into a diamine, and of their subsequent reaction with decaborane to give adduct polymers (see 2, 3). 

Hydrolysis of nitriles.1 N itriles are converted to thioamides by reaction with I (2 equivalents) at 40° overnight. Under these conditions most other functional groups are stable. Kinetic studies indicate that the reaction with nitriles is a two-step process, the first of which is analogous to an enc reaction to give a. Thioamides arc particularly useful precursors to amines by the method of Borch (2, 430 431), reaction with triethyloxonium tetrafluoroborate followed by reduction withNaBHj..- ... 

Monoamines, primary diamines and secondary amines react with nitriles to give amidines, cyclic amidines and pyrimidines, respectively, in the presence of Yb(OTF)3 as a catalyst. Reaction of ammonia with acetonitrile is shown below. 

Alkene-functionalized 1,3-diene complexes undergo regio-and stereoselechve 1,3-dipolar cycloaddition reactions with nitrile A-oxides. Related cycloaddihons of nitroalkanes in the presence of triethyl amine and phenylisocyanate afford dihydroisoxazoles. This type of cycloaddition was used in a synthesis toward macrolactin A (Scheme 163). 

Some of the physical properties of fatty acid nitriles are Hsted in Table 14 (see also Carboxylic acids). Eatty acid nitriles are produced as intermediates for a large variety of amines and amides. Estimated U.S. production capacity (1980) was >140, 000 t/yr. Eatty acid nitriles are produced from the corresponding acids by a catalytic reaction with ammonia in the Hquid phase. They have Httie use other than as intermediates but could have some utility as surfactants (qv), mst inhibitors, and plastici2ers (qv). 

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

Omission of the side chain methyl group also leads to an active analgesic, the potency of which is somewhat less than half that of the parent. Alkylation of the familiar nitrile with N (2-chioroethyl)dimethylamine gives the amine, 126. Reaction with... 

Replacement of the ketone by an amide leads to Increased potency. Hydrolysis of nitrile, 133 (obtained by alkylation of diphenylacetonitrile with the morpholine analog of the chloro-amine used in the original preparation of methadone), affords acid, 134. Conversion to the acid chloride followed by reaction with pyrrolidine affords racemoramide (135) Separation of the (+) isomer by optical resolution gives dextromoramide, an analgesic an order of magnitude more potent than methadone. 

Solvents influence the hydrogenation of oximes in much the same way as they do hydrogenation of nitriles. Acidic solvents prevent the formation of secondary amines through salt formation with the initially formed primary amine. A variety of acids have been used for this purpose (66 ), but acids cannot always be used interchangeably (43). Primary amines can be trapped also as amides by use of an anhydride solvent (2,/5,57). Ammonia prevents secondary amine formation through competition of ammonia with the primary amine in reaction with the intermediate imine. Unless the ammonia is anhydrous hydrolysis reactions may also occur. 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

Nonetheless, it was a fairly short step from octopus compounds to dendrimers, and the step was taken by Vogtle in the late 1970s when he attempted to use a cascade reaction to prepare a molecule of the dendrimer type that would now be considered a dendron rather than a fully developed dendrimer. It began with the addition of acrylonitrile to an anfine, followed by reduction of the nitrile to amine. This was followed by a further reaction with acrylonitrile, and the process was repeated several times to yield highly branched macromolecules. There were initially problems with the reduction step but these were overcome, and the preparation of these poly(propylene imine) dendrimers was later commercialized. 

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