Methods for the synthesis of the esters of 1,4-dihydropyridine-3,5-dicarbothionic acids by the thionation of the carbonyl analogs with Lawesson's reagent are developed. The influence of the substituents at the nitrogen atom on the course of the thionation reaction is considered. The physicochemical characteristics of this series of substances are analyzed; their reactivity in the reactions of N-alkylation, oxidation, and anion formation is studied.
The 1,4-dihydropyridines (I,4-DHPs), which are hydrogenated nitrogen-containing heterocycles with unusual chemical properties [i, 2] and varied biological activity [3], have recently been widely investigated.
Continuing the investigations into the synthesis of sulfur-containing 1,4-DHPs [4], we set ourselves the objective of developing methods for the isolation of unknown ethyl esters of 1,4-DHP-dicarbothionic acids unsubstituted in the 2 and 6 positions. We previously developed methods for the synthesis of esters of 2,6-dimethyl-l,4-DHP-dicarbothionic acids, studied their physicochemical properties and reactivity [5], and determined the induction and resonance constants of the ethoxythiocarbonyl substituent in the aromatic compounds [6].
Taking into account the possible superimposing of the steric factor of the 2,6-methyl groups on the electronic effects of the ethoxythiocarbonyl substituent in the 1,4-DHP ring, it was expedient to study the physicochemical properties and reactivity of the thione esters of 1,4-DHP-dicarboxylic acids unsubstituted at the 2 and 6 positions.
The 4-aryl-3,5-diethoxythiocarbonyl-l,4-DHPs (IIa-h) are not successfully obtained by cyclocondensation [7], since the corresponding thione esters of propiolic acid are hitherto unknown. Attempts at the thionation of ethyl propiolate with Lawesson's reagent [the dimer of the sulfide of p-methoxyphenylthionophosphine (XI)] were unsuccessful due to the polymerization of the esters of propiolic acid. There is a known method for the thionation of the carbonyl and alkoxycarbonyl groups in aliphatic and aromatic compounds, as well as the keto group in the indene fragment of 5-oxo-4,5-dihydroindenopyridines [8, 9]. We found that the 4-aryl-3,5-diethoxycarbonyl-l,4-DHPs (Ia-h) react readily with Lawesson's reagent, and form the new thione esters (IIa-h).
The thionation was carried out by the prolonged boiling of (Ia-h) with double the molar amount of Lawesson's reagent in dry toluene or xylene in an atmosphere of argon. The Institute of Organic Synthesis, Academy of Sciences of the Latvian SSR, Riga 226006.