Recent examples of the Pinner reaction which contain experimental details include the following.
As materials (alcohol, HCl and NH 3) are cheap, this method can be economical for large-scale synthesis. Subsequent reaction with ammonia or amines gives the amidine. The nitrile is treated with an alcohol under anhydrous conditions in the presence of hydrogen chloride or hydrogen bromide to form the imidic ester salt 3 ( Scheme 1). In the review period (1994–2003), one-third of all publications, in which amidines were synthesized from nitriles, used a Pinner reaction.
1.11).Īlthough discovered in 1877, the Pinner reaction remains the most common way of making primary amidines. Alternately, the reaction of N-methyl-1,3-diaminopropane with an excess of aliphatic nitrile gives 1-methyl-2-alkyl-1,4,5,6-tetrahydropyrimidines ( 26) in the presence of hydrogen sulfide, or a hydrogen sulfide-producing compound, in excellent yields at modest temperature ( Fig. Acetylation of the latter with acetic anhydride followed by hydrogenation of the resulting acetyl derivative ( 25) in the presence of Raney nickel catalyst and alcoholic ammonia yields the 1,4,5,6-tetrahydropyrimidines ( 26). Addition of an alkyl amine to acrylonitrile affords 2-alkylaminopropionitrile ( 24). An improved synthesis for preparing 1, 2 and 3 involves the key intermediate 1,4,5,6-tetrahydro-1,2-dimethylpyrimidine ( 26, R=Me), which may be prepared starting from acrylonitrile ( 23). A Pinner reaction involving treatment of 27 with ethanol in the presence of dry HCl, yields ethyl-2-arylacrylimide hydrochloride ( 28), which is condensed with N-methyl-1,3-diaminopropane to afford the desired tetrahydropyrimidines, pyrantel ( 1), morantel ( 2), and oxantel ( 3). Initially, the cyclic amidines were typically prepared from the requisite 2-arylacrylonitrile ( 27 ), which is easily obtained by condensation of an aryl aldehyde with cyanoacetic acid followed by decarboxylation.