3.4- Dihydrothieno pyrimidine

Similar transformations were also found on heating of 2-(but-3-ynylthio)pyrimidine (X = S) and 2-(but-3-ynylsulfonyl)pyrimidine (X = S02), 2,3-dihydrothieno[2,3-h]pyridine and l,l-dioxo-2,3-dihy-drothieno[2,3-h]pyridine, respectively being obtained (Scheme 35). 

Whereas in all previously mentioned inverse cycloaddition reactions [h]-fused pyrido annelated systems are formed, some reactions are described which lead to [c]-pyridine annelated bicyclic systems. 5-(Butynylthio)pyrimidines (R = Ph, NHCOCH3) give on heating at 180°C in nitrobenzene 5-R-2,3-dihydrothieno[2,3-c]pyridines (89T803). 5-Propynyloxymethylpyrimidines also readily undergo cycloaddition into l,3-dihydrofuro[3,4-c]pyridines (89T5151) (Scheme 39). Considerable rate enhancements were observed with quaternized pyrimidinium salts. Whereas... 

The amino group of 463 is transformed initially into carbamate compounds by treatment with several isocyanates. The carbamate intermediates were readily cyclized in base to give dihydrothieno[3,2-4]pyrimidines 464 (Equation 173) <1996MI597, 1995JOC1461>. 

Several 4-amino-2-methylthieno[2,3-synthesized directly by heating o-aminocarbonitriles 48 in a methanolic solution of acetamidine hydrochloride containing sodium ethoxide (83CPB1177). By an indirect route, 4-amino-2-substituted methyl-5,6-dihydrothieno[2,3-c/]-... 

Taylor and Pont (87JOC4287) heated 5-(3-butynylthio)-l,2,3-triazines 129 in 1,3,5-triisopropylbenzene at 232-236°C and caused a cycloaddition across the N-2/C-5 positions of the triazine ring to give, after loss of MeCN or PhCN, 5,6-dihydrothieno[2,3-d]pyrimidine 130. 

Dihydrothieno[3,4-d]pyrimidin-3(l//)-ones 337 were synthesized by a four-step reaction sequence starting from carbamates 310. The latter were selectively reduced with lithium aluminum hydride and then oxidized with activated manganese(IV) oxide to give aldehydes 334 in one-pot. Condensation of compounds 334 with ethanolamine in refluxing ethanol afforded the Schiff bases 335, which were reduced with sodium borohydride to... 

Dihydrothieno[3,4-d]pyrimidines 364 were JV-alkylated at position 3 with a variety of a-halogeno esters in the presence of base [81JAP(K)104870]. 

Chloro-3,4-dihydrothieno[2,3- i ]pyrimidines (421) are prepared when the aromatic precursors 420 are treated with excess NBH over an 8-h period at room temperature. ... 

The action of NaBH4 on 141 (X = X = Cl) gave 2-chloro-3,4-dihydro-thieno[3,4-d]pyrimidines 142, which were used for the synthesis of 2-substituted dihydrothieno[3,4-d]pyrimidines via nucleophilic substitution reactions (81JMC376). 

The reactions of aminocarbonyl derivatives of thiophene (21) with potassium thiocyanate afforded (4-oxo-3,4-dihydrothieno[2,3-acetic acid derivatives (22) in yields up to 51%. Analogously, the isomeric aminocarbonyl derivative 23 gave ethyl (7-cyano-6-methylthio-4-oxo-3,4-dihydrothieno[3,2-J]pyrimi-din-2-ylthio)acetate (24) in 85% yield (2000H2363). 

Benzamido-3-cyano-4,5-dihydrothiophenes (321) cyclize at 120°C with cyclohexylamine, morpholine, piperidine, and pyrrolidine to the corresponding 4-amino-2-phenyl-5,6-dihydrothieno [2,3-d ] pyrimidines (322).181 However, when 321 and 2 equivalents of dimethylamine hydrochloride in pyridine were refluxed for 5 hr, the 4-oxothieno [2,3-d] pyrimidine 323 was formed nearly quantitatively181 (Scheme 92). Ethyl iV-(3-cyano-4,5-dihydro-2-thienyl)oxamates (324) give, with cyanomethylene compounds in the presence of triethylamine, thieno[2,3-d]pyrimidines (325).182... 

Pyrimidine derivatives do not generally have positive flavor notes and are considered neutral to poor. Some pyrimidine-derived flavors (although not found in tobacco or tobacco smoke) have meaty notes. There are also some pyrimidine flavorants that do possess good flavor potential for tobacco products, for example, 2-methyl-5,7-dihydrothieno[3,4- (]pyrimidine. This compound contains a bicyclic ring structure and has been identified in tobacco. 2-Methyl-5,7-dihydrothieno[3,4- (]pyrimidine is said to have a fresh roasted, sweet nut flavor with a popcorn character (17B22). It is a compound listed by Doull et al. as an ingredient in flavor formulations used by one or more members of the U.S. tobacco industry (1053). 

Vovk MV, Bolbut AV, Boiko VI, Pirozhenko W, Chemega AN, Tolmachev AA (2004) Synthesis of 2-trihalomethyl-3,4-dihydrothieno[2,3-d]pyrimidin-4-ones. Chem Heterocycl Compd 40 370-376... 

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