1966 Volume 86 Issue 9 Pages 815-822
Some of the polysubstituted 4-phenylpyridine derivatives show pharmacological activity and, therefore, synthesis was attempted for compounds having a structure similar to the 4-phenylpyridine skeleton present in the structure of streptonigrin. First, examinations were made for the synthesis of C-D rings in streptonigrin and synthesis was effected for 4-(3, 4-methylenedioxyphenyl)-3-cyano-5-ethoxycarbonyl-6-methyl-2-quinolylpyridine, which has a streptonigrin skeleton and a substituent that could be derived to its C ring. The methods used for these syntheses can be classifield into the following three : (1) Condensation of α-cyanocinnamide and ethyl 3-aminocrotonate, (2) Condensation of cyanoacetamide with the product of the Claisen-Schmidt reaction, and (3) the Hantzsch-type synthesis. 4-Phenylpyridine was obtained as the product using methods (1) and (2). The condensation intermediate in these reactions was dihydropyridone compound and its oxidation to pyridone gave a poor yield of the product but the oxidation product was obtained directly when the substituent in the 4-position was piperonal. Attempt to introduce one more substituent into the pyridine ring by the method (2) did not materialize. Oxidation of 1, 4-dihydropyridine derivatives (XXa∼b), obtained by method (3), to pyridine derivatives (XXIa∼b) was not effected by the use of dilute nitric acid, chromic acid, palladium black, or palladium carbon, and it is interesting that the oxidation product was finally obtained by heating the dihydro compounds in a sealed tube with mercury acetate to above the melting point of them.
