Cyclocondensation of 5-benzoyl-3-ethoxycarbonyl-6-methylthio-1-R-1,2-dihydropyrid-2-ones with heterocyclic N,N-and N,C-1,3-dinucleophiles

Abstract

Derivatives of 3-aroyl-2-(methylthio)pyridine are valuable starting materials for obtaining condensed nitrogen-containing heterosystems. In spite of the significant number of studies devoted to the synthesis of these compounds [1-7] their further conversions have not been studied. This is probably explained both by the nonselectivity of the reactions obtaining them [1-3] and the difficulty of availability of the initial reactants [4][5][6][7].

Recyclization of 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydro-pyridin-2-ones into 1,6-annelated derivatives of 3-alkylcarbamoyl-5-benzoylpyridin-2-one

“…The reaction products are therefore not derivatives of 5-benzoyl-3-heteryl-2H-2-pyranone, as we proposed previously [3,4], but are 6-alkylcarbamoyl-8-benzoyl-5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridines 3a,b, 7-alkylcarbamoyl-9-benzo-yl-6-oxo-1,2,3,5-tetrahydro-2H-pyrido[1,2-a]pyrimidines 3c,d, and 1-alkyl-6-(1-alkyl-5-benzoyl-…”

“…In the last two cases the reaction proceeds as a recyclization [3,4].The aim of the present work was to establish unequivocally the structure of the products of recyclization, to study the limits of its application, to investigate the effect of the ratio of starting materials on the direction of the reaction, and to clarify the sequence of formation of intermediate compounds.It was discovered that 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones 1a,b react with an excess of diaminoethane 2a and 1,3-diaminopropane 2b nonselectively. The reaction products are therefore not derivatives of 5-benzoyl-3-heteryl-2H-2-pyranone, as we proposed previously [3,4], but are 6-alkylcarbamoyl-8-benzoyl-5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridines 3a,b, 7-alkylcarbamoyl-9-benzo-yl-6-oxo-1,2,3,5-tetrahydro-2H-pyrido[1,2-a]pyrimidines 3c,d, and 1-alkyl-6-(1-alkyl-5-benzoyl-…”

“…The latter are also formed on hydrolysis of the initial 1,2-dihydropyridin-2-ones 1a,b, occurring under the action of water and triethylamine [3]. The yields of compounds 3a-d and 4a,b were 39-69 and 24-49% respectively.…”

Heterocyclization of thioamides containing an active methylene group (review)

“…It was established [86] that the acidity (pK a ) of the thioamides and the reactivity of the 3-aryl-2-propenoyl chlorides (the latter can be determined indirectly from the pK a value of the corresponding 3-aryl-2-propenoic acid) are the main factors affecting the regioselectivity of this cyclization. The reaction of 3-oxopropanethioamides 168 with diethyl ethoxymethylenemalonate (DEEM), the ethoxy group of which is a good nucleofuge (as follows from the reviews [17,89]), was investigated in [87,88]. As a result conditions were found for the preparative one-pot synthesis of 5-benzoyl-3-ethoxycarbonyl-6-methylthio-1-R-1,2-dihydropyridin-2-ones 169, and the possibility of using them for the selective production of condensed polycyclic heterosystems, including previously undescribed pyrido [2,3-d] pyrimidine derivatives 170, 171, 173, and 174, was demonstrated [87,88].…”

“…The reaction of 3-oxopropanethioamides 168 with diethyl ethoxymethylenemalonate (DEEM), the ethoxy group of which is a good nucleofuge (as follows from the reviews [17,89]), was investigated in [87,88]. As a result conditions were found for the preparative one-pot synthesis of 5-benzoyl-3-ethoxycarbonyl-6-methylthio-1-R-1,2-dihydropyridin-2-ones 169, and the possibility of using them for the selective production of condensed polycyclic heterosystems, including previously undescribed pyrido [2,3-d] pyrimidine derivatives 170, 171, 173, and 174, was demonstrated [87,88]. During an attempt to realize similar cyclizations for 1-R-1,2-dihydropyridin-2-ones 176 with 1,4-and 1,5-dinucleophiles (1,2-diaminobenzene, 1-amino-2-mercaptobenzene, 1,2-diaminoethane, 1,3-diaminopropane) it was not possible to obtain the expected 1,4-diazepines (thiazepines) -the products were derivatives of 6-(Ramino)-5-benzoyl-2H-2-pyranone 177 and 178 [90,91].…”