Synthesis of pyridine derivatives by the three-component condensation of a β-dicarbonyl compound, β-enaminocarbonyl compound, and ethyl orthoformate

Abstract

The major products of the three-component condensation of a fl-dicarbonyl compound flenaminocarbonyl compound, and ethyl 3, 3, 6, 6-tetramethyl-l,2, 3, 4, 5, 6, 7, 8-octahydro-l,8-acridinedione [5, 6]. Octahydroacridines Ib and Ic were obtained [7] by the condensation of enamino ketones I/Ib and mc from dimedone and 1,3-cyclohexanedione (lie) with ethyl orthoformate in acetic acid. The maximum yields were 44% for Ia, 53% for Ib, and 21% for Ic (Table I). Analysis of these methods for the preparation of symmetrical pyridine derivatives Ia-c led us to study the reaction of a three-component system consisting of a ~-dicarbonyl compound II, ~-enaminocarbonyl compound III, and ethyl orthoformate with the aim of increasing the yield of products Ia-c as well as to obtain new products I, including asymmetric derivatives.The reaction of ethyl orthoformate with [3-dicarbonyl compounds IIa-c presumably leads to the formation of unsaturated diketoesters which, as shown [5] in the case of ethyl ethoxymethylenacetoacetate (IVa), react with enamines IIIa-c (obtained from Ha-c, respectively) to give products I.The reaction was carried out in the presence of acetic acid in accordance with the procedure described [8] for the synthesis of ~-enamino diketones from ~-diketones, primary amines, and ethyl orthoformate. Indeed, pyridine derivatives Ia-e were obtained as the major products. Minor products, namely, tricarbonyl compounds Va,b,d as well as tetrahydropyridine derivative VI (obtained when IIa and Ilia were the starting reagents) (Scheme I) were also isolated from the reaction mixture in the reaction with ethyl orthoformate, ethyl acetoacetate, dimedone, and the resultant enamines (Ha and Ilia, lib and Ilib, and lib and NIa).The structures of these products were established by the spectral and elemental analysis data (Tables 1 and 2). Thus, the PMR spectra of lia-e have a characteristic singlet for 4-H at 8.68-8.82 ppm and signals, whose position, shape, and intensity correspond to the substituent protons. The PMR spectra of imines Va,b,d have characteristic

3-Amino-5,5-dimethylcyclohex-2-enone in the synthesis of heterocyclic compounds (review)

“…Decahydroacridinedione 82e showed comparatively high activity and selectivity in relation to colon bacillus E. coli 675 [51]. The acridines 94 were produced during research on agents acting on the central nervous system [56]. Dimethylacridinediones 87 can be regarded as a new class of Ca 2+ ions exchange regulators [52].…”

“…The reaction of the ethyl orthoformate with the dimedone leads to the formation of the ether 95. The latter vinylates the enaminone 1 at the C(2) atom, leading to the dienamine 96, the cyclization of which gives the tetramethylacridinediones 97 [56]. …”

A Practical and One-Pot Procedure for the Synthesis of 3-Amino-2-cyclohexen-1-one from 3-Aminophenol

“…3-Amino-2-cyclohexen-1-one ( 1 ), a cyclic enaminone, is a useful intermediate in organic synthesis as a synthon for the construction of biologically active compounds (such as dopamine autoreceptor agonists, acetylcholinesterase inhibitors, oxytocin antagonists, anticonvulsants, and K ATP channel openers) and functionally interesting heterocyclic compounds (such as pyridines or quinolines, − azaazulenes, sesquiterpenes, tetrahydro-1,3-oxazines, and angucycilinone 5-aza-analogues). The generally and industrially employed synthetic methods for the preparation of 1,3-amino-2-cyclohexen-1-one ( 1 ) are classified into three categories (Scheme ).…”