One‐pot New Barbituric Acid Derivatives Derived from the Reaction of Barbituric Acids with BrCN and Ketones

Abstract

Reaction of cyclic b-dicarbonyl compounds such as pyrimidine-(1H,3H,5H)-2,4,6-trione (BA), 1,3dimethyl pyrimidine-(1H,3H,5H)-2,4,6-trione (DMBA) and 2-thioxo-pyrimidine-(1H,3H,5H)-4,6-dione (TBA) with cyanogen bromide in acetone and 2-butanone in the presence of triethylamine afforded a new class of stable heterocyclic spiro[furo[2,3-d]pyrimidine-6,5¢-pyrimidine]2,2¢,4,4¢,6¢(3H,3¢H,5H)-pentaones (dimeric forms of barbiturate) at 0°C and ambient temperature. Structure elucidation was carried out by X-ray crystallographic, 1 H NMR, 13 C NMR, two dimensional NMR, FT-IR spectra, mass spectrometry and elemental analysis. The mechanism of product formation is discussed. The reaction of DMBA with cyanogen bromide in the presence of triethylamine also afforded trimeric form of barbiturate of uracil derivatives in good yield. The reaction of selected acyclic b-dicarbonyl compounds with cyanogen bromide in the presence of triethylamine in acetone and/or diethyl ether has also been investigated under the same condition. Diethyl malonate and ethyl cyanoacetate brominated and also ethyl acetocetate both brominated and cyanated on active methylene via cyanogen bromide. Scheme I Reaction of cyclic b-dicarbonyls (1a-e)with cyanogen bromide and ketones (2)(3)(4)(5) in the presence of triethylamine Scheme II Proposed mechanism for the preparation of 6a as representative One-pot New Barbituric Acid DerivativesScheme III Knoevenagel condensation, Michael addition and cyclization mechanism for the formation of 7b as representative Scheme IV Reaction of 1b with cyanogen bromide in various ketones (2-5) in the presence of triethylamine for the synthesis of 16b

One-pot Four Component Reaction of Unsymmetrical 1-Methylbarbituric Acid with BrCN and Various Aldehydes in the Presence of Et3N and/or Pyridine

“…As a part of our current studies on barbituric acids and its reaction with cyanogen bromide [32][33][34] and our interest in the chemistry of cyanogen bromide we have investigated the unexpected bromination of 1 by cyanogen bromide. The bromination of 1-MBA by cyanogen bromide is unexpected and was resulted as salts of 3 and/or 4.…”

“…Intramolecular rearrangement of this intermediate produces 5-bromo-1-methylpyrimidine-(1H, 3H,5H)-2,4,6-trione (11) followed by loss of HCN to form the salts of 3 and/or 4 (obtained from triethylamine and pyridine as a base, respectively) according to similar bromination of 1-alkyl-imidazoles with BrCN 29 and bromination of symmetric (thio)barbituric acids. 32,33 No 1-methyl-…”

“…Nonetheless this compound also is useful brominating and cyanating agent as; the bromination and cyanation of imidazoles, 29 free radical reaction with alkanes that result in bromination of alkanes 30 and α-bromination of β-aminoenones. 31 More recently, we have reported the reaction of (thio)barbituric acids (as a symmetrical barbituric acids) with aldehydes 32 and ketones 33 in the presence of cyanogen bromide and triethylamine. Nonetheless, there is no report about the reaction of 1-methylbarbituric acid (1-MBA) as an unsymmetrical barbituric acid with cyanogen bromide and aldehydes in the literature.…”

“…More recently, we have investigated the reaction of symmetric barbituric acids 25-27 with cyanogen bromide and various aldehydes 32 and ketones 33 in the presence of Et 3 N. It has been found that the salts of 29-31, 5-alkyl- 32 were formed in the reaction of 25-27 with aldehydes in the presence of cyanogen bromide and triethylamine (Fig. 4).…”

“…4). And of trimeric form of barbiturate, (33) derived from DMBA 26 in the reaction with ketone in the presence of cyanogen bromide and triethylamine by new chemical method 33 Dryhurst et al reported the synthesis of 33 by electrochemical method [43][44][45] . We also reported the crystal structure of dimeric barbiturate form (32) derived from the reaction of 26 with acetone in the presence of cyanogen bromide and triethylamine.…”