Synthesis of 2,3‐dihydro‐1,3‐thiazin‐4(1H)‐ ones and their remarkably facile recyclization to 2,3‐dihydropyrimidin‐4(1H)‐ones

Abstract

Functionalized 2,3‐dihydro‐1,3‐thiazin‐4(1H)‐one derivatives have been synthesized by cyclocondensation of 3‐alkyl(aryl)amino‐2‐cyano‐3‐mercaptoacrylamides with aldehydes and ketones under acidic catalysis. 6‐Alkyl(aryl)amino‐5‐cyano‐2,3‐dihy‐ dro‐1,3‐thiazin‐4(1H)‐ones, when treated with a dilute solution of potassium hydroxide, are converted into the potassium salts of isomeric compounds, 1‐alkyl‐ (aryl)‐5‐cyano‐6‐mercapto‐2,3‐dihydropyrimidin‐ 4(1H)‐ones. Alkylation of the latter with dimethyl sulfate in situ furnishes 1‐alkyl(aryl)‐6‐alkylthio‐5‐ cyano‐2,3‐dihydropyrimidin‐4(1H)‐ones, whereas boiling them in ethanol with an excess of hydrochloric acid leads to starting 2,3‐dihydro‐1,3‐thiazin‐4(1H)‐ones. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:426–436, 2005; Published online in Wiley InterScience (http://www.interscience.wiley.com). DOI 10.1002/hc.20129

Synthesis of functionalized 2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones and their recyclization to 2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-ones

“…Heating 3-alkyl(aryl)amino-2-cyano-3-mercaptoacrylamides 1a, b with aldehydes and ketones 2a-h in the presence of a catalytic amount of acid as previously described [8], we obtained 2,3-dihydro-1,3-thiazin-4(1H)-ones 3a-l. Chloroacetone 4a, α-chloro-tert-butylmethylketone 4b, and bromoacetophenone 4c were used as alkylating agents for further heterocyclization (Scheme 1). It is found that short boiling (for 1-2 h) of compounds 3 and 4 with two equivalents of triethylamine in ethanol…”

“…recyclize under the action of basic agents like potassium hydroxide or triethylamine yielding the thiolates of 1-substituted 5-cyano-6-mercapto-2,3-dihydropyrimidin-4(1H)-ones [8]. On alkylating the latter at the sulfur atom with dimethyl sulfate or benzyl chloride, they furnished 6-alkylthio-5-cyano-2,3-dihydropyrimidin-4(1H)-ones.…”

Chemistry of heterocyclic compounds at the Institute of Organic Chemistry, National Academy of Sciences of Ukraine (Review)

“…During heating in acetic acid it was found that they are susceptible to transformation into the isomeric heterocyclic system of 2,3-dihydrothieno [3,4-d]pyrimidin-4-(1H)-one. The effect of temperature and the nature of the substituents on the course of this process was studied in detail [91,92].…”

“…V. A. Sukach, A. V. Bolbut, and M. V. Vovk proposed two procedural approaches to the synthesis of new highly functionalized derivatives of 2,3(3,4)-dihydro-1,3-azin-4(2)-ones and their condensed analogs. The first of them involves the principle of the construction of the 1,3-azine ring by a [5+1] heterocyclization mechanism and is based on the reaction of available 2-alkyl(aryl)amino-1-cyano-2-mercapto-acrylamides with carbonyl compounds [91]. The second is based on a new variant of the formation of the heterocyclic ring by a [3+3] cyclocondensation mechanism, which was realized successfully on examples of the reaction of 1-chloroalkyl isocyanates with 1,3-C,N-, 1,3-C,O-, and 1,3-C,S-binucleophilic reagents [91,92].…”

“…The first of them involves the principle of the construction of the 1,3-azine ring by a [5+1] heterocyclization mechanism and is based on the reaction of available 2-alkyl(aryl)amino-1-cyano-2-mercapto-acrylamides with carbonyl compounds [91]. The second is based on a new variant of the formation of the heterocyclic ring by a [3+3] cyclocondensation mechanism, which was realized successfully on examples of the reaction of 1-chloroalkyl isocyanates with 1,3-C,N-, 1,3-C,O-, and 1,3-C,S-binucleophilic reagents [91,92]. As a result of the experiments the published data concerning the structure of the products from the condensation of 2-alkyl(aryl)amino-1-cyanacryl-2-mercaptoamides with aldehydes and ketones were rejected, and it was established that they are in fact derivatives of 6-alkyl(aryl)amino-2,3-dihydro-1,3-thiazin-4(1H)-one.…”