One-step synthesis of a novel heterocyclic system: Spiro[[1,4]thiazino-[4,3-a]quinoline-5,5′-pyrimidine]

Abstract

We have observed that when 2-thiomorpholino-5-trifluoromethylbenzaldehyde is reacted with barbituric acids under Knoevenagel condensation conditions, a novel heterocyclic system is formed: 1,2,4,4a,5,6-hexahydrospiro [[1,4]thiazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'-triones 1a,b, i.e., two new C-C bonds are formed during the reaction. The reaction occurs through the o-vinyl derivatives 3 [1, 2] followed by their cyclization according to a tert-amino effect mechanism [3,4]. When monosubstituted barbituric acids were used, two isomers could be formed. We have shown that with monosubstituted barbituric acid 2b, a 1:1 mixture of spiro-linked condensed [1,2-a]quinolines 1b is formed in 78% yield. One of the isomers can be isolated in 33% yield by fractional crystallization from aqueous alcohol.

tert-Amino effect: the Meth-Cohn and Reinhoudt reactions (Review)

“…We showed [38] that with the monosubstituted barbituric acid 40b a 1:1 mixture of spiro-coupled fused [1,2-a]quinolines 41b was formed in 79% yield. One of the isomers could be isolated with a yield of 33% by fractional crystallization from aqueous alcohol.…”

4‐Methyl morpholinium bis‐(thio)barbiturates: Synthesis, structure, anticancer evaluation, and CoMFA study

“…[ 10 ] Other electrophiles such as carbodiimides, benzophenones, 2,2′‐bipyridyl, and erythrolactols react with BA to produce diaminoethylenebarbiturates, [ 11 ] triphenylmethylium salt, [ 12 ] 5,5′‐(2‐pyrilidine)bisbarbituric acid, [ 13 ] spirobarbituric deoxyribonucleoside, [ 14 ] and spiro‐linked condensed [1,2‐ α ]quinolones. [ 15 ] One‐pot reaction of (thio)barbituric acids with aldehydes and cyanogen bromide yield spiro furo[2,3‐ d ] pyrimidines. [ 16–21 ]…”

Bifunctionalized linked bis-spiro[furo[2,3-d]pyrimidine-6,5'- pyrimidine]2,2',4,4',6'(3H,3'H,5H)-pentaones derived from one-pot reaction of (thio)barbituric acids with aromatic dialdehydes and BrCN in the presence of Et_3N

“…9 For instance, determination of niketamide 10 and niacinamide 11 through the reaction of BA and cyanogen bromide has been used. BA derivatives can act as nucleophiles and react with different electrophiles such as carbodiimides, 12 benzophenone derivatives, 13 and 2,2 -bipyridil to form 5,5 -(2-pyrilidine)bisbarbituric acid, 14,15 C 60 molecules, 16 and erythrolactol to obtain spiro-barbituric deoxyribonucleoside, 17 spiro-linked condensed [1,2-a]quinolines, 18 πconjugated systems containing BA, and 1,3-dimethyl barbituric acid (DMBA) derivatives. 19 More recently, a new class of stable heterocyclic 5-alkyl and/or 5-aryl-1 H ,1 H-spiro[furo [2,3-d ]pyrimidine-6,5 -pyrimidine]2,2 ,4,4 ,6 (3 H ,3 H, 5 H) pentaones has been reported by our group from one-pot reactions between (thio)barbituric acids and aromatic and aliphatic mono-aldehydes 20,21 and ketones 22 in the presence of cyanogen bromide and triethylamine.…”