Enaminones as building blocks in heterocyclic synthesis: New syntheses of nicotinic acid and thienopyridine derivatives

Abstract

Reacting 1,3‐diphenyl‐propan‐2‐one with equimolecular amount of dimethylformamide dimethylacetal afforded the enaminone 4. This when reacted with another equimolecular amount of dimethylformamide dimethylacetal afforded the dienaminone 5. Compound 4 condenses with cyanothioacetamide and with cyanoacetamide to yield 2‐thioxo‐ and 2‐oxo‐pyridine‐3‐carbonitrile derivatives 6a,b respectively. Compound 6a reacted with α‐chloroacetone 8 to yield the thieno[2,3‐b]pyridine derivative 10 that cyclized further into 4,7,8‐trisubstituted pyrido[2′,3′:2,3] thieno[4,5‐d]pyrimidine 12. Compound 4 also afforded 2,5,6‐trisubstituted nicotinic acid ethyl ester 13 by reaction with ethyl acetoacetate in acetic acid in the presence of ammonium acetate. The dienaminone 5 reacted with acetic acid, ammonium acetate/acetic acid, phenylhydrazine and 5‐amino‐3‐methylpyrazole yielding 3,5‐diphenyl‐pyran‐4‐one 15a, 3,5‐diphenyl‐1H‐pyridin‐4‐one 15b and 1,3,5‐trisubstituted pyridin‐4‐ones 16a‐b.

Recent developments in chemical reactivity of N,N-dimethylenamino ketones as synthons for various heterocycles

“…The alternative structure 341a which could have resulted from initial condensation of the active methylene with the carbonyl function, should display a doublet for the pyridine ring CH. 127 Treatment of dimethylaminomethylene compound 228a with cyanothioacetamide, cyanoacetamide or anion of malononitrile dimer in dry DMF and sodium hydride led to 5-benzoylpyridines 345a-c rather than isomeric 344a-c based on the mass spectra (MS) of the isolated products. Additionally, the IR spectrum showed the disappearance of the cyano group so that structure 345b became 346 upon hydrolysis (Scheme 96).…”

Chemistry of 2-Arylhydrazonals: Utility of Substituted 2-Arylhydrazono-3-Oxoalkanals as Precursors for 3-Oxoalkanonitriles, 3-Aminoisoxazole and 1,2,3- and 1,2,4-Triazoles

“…1,2 The utility of the 2-arylhydrazonals 2 as building blocks in heterocyclic chemistry has been extensively investigated in our laboratories in the past few years. [3][4][5][6][7][8][9][10][11][12][13] New efficient routes to cinnolines, 3,4 pyridines, [5][6][7] pyridazines, [8][9][10] pyrazoles and isoxazoles [11][12][13] have been described in our earlier work. Very recently, we reported an efficient synthesis of 2-arylhydrazono-3-oxoalkanonitrile 3 by reacting 2 with hydroxylamine hydrochloride in a domestic microwave oven.…”

Efficient Synthesis of β-Enaminones and β-Enaminoesters Catalyzed by Gold (I)/Silver (I) under Solvent-Free Conditions

“…β-Enaminones and β-enaminoesters are highly useful building blocks [1,2,3], which can be further transformed into valuable natural therapeutic and biologically active compounds such as anticonvulsivant [4,5], anti-inflammatory [6], and antitumor agents [7,8]. Moreover, they are useful intermediates for the preparation of aminoesters [9], α,β-aminoacids [10,11], peptides [12], quinolines [13,14], azocompounds [15,16] and alkaloids [17,18,19].…”