Isothiocyanates pyrimidine ring

The synthesis of the pyrimidine ring represents a well-studied group of heterocyclization reactions based on enamines. One of the important approaches involves the reaction of enamines with assorted isocyanates and isothiocyanates. Thus, a reaction of enaminonitriles with benzyl isocyanate or phenyl isocyanate gives C- and N-adducts (190a and 190b, respectively) or their mixtures, which are transformed in a single step into 4-pyrimidinone (191) and 2-pyrimidinone (192) derivatives (94JHC329). The... 

Besides chlorine,43 a variety of leaving groups in the 2-position such as other halogens, alkoxy, sulfonyl substituents, etc., are common.44 The substituted carboxamide is metalated in the 2-position with sodium hydride and (V-acylatcd by an TV-carbamylimidazole,43 an isocyanate or an isothiocyanate,44 and the resulting urea side chain then cyclizes to give the pyrimidine ring. 

In further reactions of N-phenylbenzimidoyl chloride (56), methyl isothiocyanate and stannic chloride, in nitrobenzene at 110°C, gave 2-phenyl-4-methylthioquinazoline in moderate yield JV-phenyltrichloroacetimidoyl chloride reacted similarly.41 Then, in one of the few reactions that produce a halogenated pyrimidine ring, the chloride (56) with cyanogen bromide and stannic chloride (in nitrobenzene at 150°C) gave 4-bromo-2-phenylquinazo-line in excellent yield.41... 

On the other hand, thiazolo[5,4-d] pyrimidines also obtained from 5-aminothiazole derivatives, are prepared from aminomalononitrile (or its derivatives) and isothiocyanates [141] or thioesters [142]. The next to 5-amino and 4-cyano (or conforming carboxamide or ester groups) on the thiazole ring are proper functionalities to concept a fused pyrimidine ring system. 7-Aminothiazolo[5,4-d]pyrimidines can be prepared from 5-amino-4-cyanothiazoles by reaction... 

Without additional reagents Pyrimidine ring from isothiocyanates... 

Reactions of enamines with monoimines of o-quinones afford polycylic compounds 228 with an oxazine ring (86MI2).Trifluoroacetylation of enamines with trifluoroacetic acid takes place in the /3-position of the enamine. Ketones (229) thus formed in an acidic medium afford fused 1,3-oxazines (230) (82JOC3339). Treatment of amines with silyl isothiocyanate gives not only pyrimidine derivatives but also l,3-oxazine-4-thiones (231) (81CCC2696). 

In the reaction of the isothiocyanate (516) the initially formed thiourea is cyclized to a pyrimidine-2-thione ring, the quinazoline (517), which is unambiguously N-3 substituted and therefore on acid catalysis yields the thiazolidine (518). The true configuration of... 

Suitable educts for this type of cyclization have been obtained by the reaction of 2-aminonico-tinic esters with isocyanates or isothiocyanates to give the corresponding ureas or thioureas. Ring formation to pyrido[2,3-rf]pyrimidines, e.g. 19, occurs at elevated temperatures27 or under basic conditions.28,29 Since, depending on the substitution pattern of the 2-aminonico-tinic ester, the intermediate thiourea may cyclize spontaneously, these reactions are described in detail elsewhere (vide infra). 

The synthesis of thiazolo[4,5-d]pyrimidines has been successfully accomplished by various methods. 4-Amino-5-ethoxycarbonylthiazole derivative has been cyclized to thiazolo[4,5-d]pyrimidine by its reaction with phenyl isothiocyanate [87], Many 4-amino-5-carbamoylthiazole derivatives have been cyclized to the corresponding thiazolo[4,5-d]pyrimidines using triethyl orthoformate/acetic anhydride mixture [88-91], Moreover, 4-amino-5-cyano thiazoles have been used to prepare the same fused ring system via their reaction with triethyl orthoformate, followed by treatment of the intermediate with hydrogen sulfide, guanidine, amines, and isothiocyanates [92, 93], Other thiazolo[4,5-d]pyrimidines have been obtained from 4-amino-5-cyano, carbamoyl, or ethoxycarbonyl thiazoles via cyclization with acetic anhydride [94] or formic acid [95],... 

IsothiazoIo[3,4-e/]pyriiiiidines.—The oxidative ring-closure of 4-aminopyrimidine-5-thioamides (84) provides 3-aminoisothiazolo[3,4-substituted uracils, which are accessible by the interaction of 4-amino-uracils with isothiocyanates (including acyl and sulphonyl isothiocyanates), readily afford a series of 3-amino-4,5,6,7-tetrahydroisothiazolo-[3,4-rf]pyrimidine-4,6-diones by the same cyclization. ... 

Cyclic thioureas containing six-membered rings condense with aromatic isothiocyanates in the presence of mercury bis(phenylacetylide), in a similar manner to that described previously (see p. 401) for 2-mercaptoimidazoline, to give, eventually, the methiodide (84). Thiazolo[3,2-a]pyrimidine-5,7-diones, on alcoholysis or aminolysis, give the corresponding 2-substituted thiazoles [SO R = C(0)CHsCOsAlk or C(0)CHaC(0)NHAlk]. 3 ... 

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