Crystalline derivatives preparation nitriles

Crystalline derivatives of aliphatic nitriles may be prepared by an application of the Hoesch reaction. Equimolecular proportions of phloroglucinol and the nitrile react in dry ethereal solution in the presence of anhydrous zinc chloride and hydrogen chloride to give an imine hydrochloride, which is converted into a solid alkyl trihydroxyphenyl ketone by hydrolysis. The alkyl 2,4,6-trihydroxy-phenyl ketones are usually highly crystalline solids of sharp melting point and are purified by recrystallisation from hot water. Many contain water of crystallisation which can be removed by drying in vacuo at about 100 °C the melting points of both the hydrated and anhydrous compound should be determined. 

Fry, in a search for an intermediate capable of undergoing stereospecific cyclization to 11/3-alkylbenzomorphans, studied the 2,3-cis and trans isomers of 2-benzyl-l,3,4-trimethyl-l,2,3,6-tetrahydropyridine (Scheme 4.11). These were prepared from the iminium dienes (80 and 81) isolated as crystalline perchlorates from benzyl Grignard attack on 1,3,4-trimethylpyridinium bromide. The isomeric dienes were differentiated through their cyano derivatives (82 and 83), which on borohydride reduction gave the isomeric tetrahy-dropyridines, 84 and 85. Elimination of HCN from 82 gave the iminium diene (86) isomeric with 81. Addition of nitrile to 81 followed by borohydride reduction resulted in the appropriate trans tetrahydropyridine (88) that cyclized to the 11/3-methylbenzomorphan (89). 

The cyanide ion, which is strongly nucleophilic, reacts, even in alkaline solution, with 17. The reaction proceeds stereospecifically, affording crystalline 2-amino-2,6-anhydro-2-deoxy-D-idononitrile (38), which gives an N-nitroso derivative (37). The configuration at C-2 was proved by hydrogenation of the nitrile, with subsequent acetylation. The l,2-bis(acetamido)-3,4,5-tri-0-acetyl-2,6-anhydro-l,2-di-deoxy-D-iditol (39) had a rotation numerically the same as, but of opposite sign to, that of the enantiomorph prepared in another wav (see Section 11, 2 p. 137). 

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