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Elektrophile und nucleophile Substitution partiell hydrierter Nicotinsäure‐Derivate . 11. Mitt. über synthetische Indol‐Verbindungen
Author(s) -
Troxler F.
Publication year - 1973
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19730560130
Subject(s) - chemistry , iminium , enamine , medicinal chemistry , nucleophile , alkylation , electrophile , amide , pyridine , stereochemistry , catalysis , organic chemistry
Abstract 1‐Methyl‐1,4‐dihydronicotinamide ( 1 ) 2 reacts with gramines to the corresponding 1‐methyl‐5‐skatyl‐1,4‐dihydronicotinamides ( 3 ), the structures of which have been proved by conversion of 6 , a homologue of 3 , into dimethyl pyridine‐3,5‐dicarboxylate ( 11 ). Palladium/H 1 reduces 3 to the 1,4,5,6‐tetrahydronicotinamides 12 , which are hydrogenated with platinum/H 1 to a mixture of the diastereomeric 1‐methyl‐5‐skatyl‐nipecotinamides 14 and 15 . Alkaline hydrolysis converts the trans ‐amide 15 to the cis ‐carboxylic acid 16 . Enamine alkylation of 1 with benzylbromide and subsequent catalytic reduction leads in low yield to 5‐benzyl‐1‐methyl 1,4,5,6‐tetrahydronicotinamide ( 18 ). 1‐Substituted 1,4,5,6‐tetrahydronicotinic acid derivative 19 are alkylated by strong electrophilic halides to iminium salts 20 , which, after catalytic reduction form 3,3‐disubstituted piperidines 21 generally in high yield. The factors influencing the enamine alkylation are discussed. The addition of nucleophiles to iminium salts 20 has been studied. Thus the 1‐methyl‐hexahydro‐2 H ‐pyrrolo[3.4‐ b ]pyridines 32 und 33 were prepared by treatment of 20 with cyanide, followed by reduction with LiAlH 4 in the case of 33 . Intramolecular addition of nucleophiles onto 20 formed the pyrido[2 3‐ a ]carbazole 35 , the indolo[2.3‐ a ]quinolizines 37 and the benzopyrano[2.3‐ b ]pyridines 43, 44 and 46 . It has been shown that in the iminium salts 20 the group X can eliminate either, if X CONH 2 , by a fragmentation mechanism or, if X CX by nucleophilic attack.