Pyrimidine formation thiourea

Methylene derivatives formed from alloxan can serve as bis-electrophiles and react with species such as guanidine to give pyrimido[4,5-tf pyrimidines directly (Equations 91 and 92). Formation of the Michael acceptor and the corresponding cyclization with thiourea can be carried out either in a single step (Equation 93) <2003RCB2457> or with isolation of the intermediate (Scheme 58) <2003SC3747> in either case, the process is reported to proceed most efficiently in the solid state under microwave irradiation. 

A myriad of types of fused-ring pyrimidines derived from thioureas have been reported in the literature. For example, Howard and Lindsey387 reported the [l,3]-dithiino[5,4-d]pyrimidine ring system 223, and other workers made the octahydrobenzo[6]thieno[2,3-d]pyrimidirie 224 in 90% yield.388 The formation of both of these products was via a base-promoted condensation of a thiourea with a carbethoxy group however, in the former case the reaction was intermolecular and in the latter, intramolecular. Other unusual fused systems of this type have... 

The reactions of thiourea and guanidine with cycloalkanones are carried out in the same manner [101]. But it is worthwhile noting that muticomponent reactions of urea-like compounds with ketones, containing an activated methyl or methyle-negroup, often do not stop after the formation of a pyrimidine ring. In fact numerous derived condensation processes can lead to more complicated polycyclic compounds, which are especially typical for the reaction of cycloalkanones [101]. 

Treatment of 3-(2-pyridylimino)-3f/-l, 2,4-thiadiazolo[4,3-a]pyrimidine (304 R=2-pyridyl) with either 10% ethanolic HC1 or NaOH resulted in the formation of 2-(2-pyridylimino)-2//-l,2,4-thiadiazolo[2,3-fl]pyrimidine (305 R=2-pyridyl), which was alternatively synthesized by the action of sul-furyl chloride on thiourea 306 (74JOC3783). Under similar conditions 5,7-dimethyl-3-(2,6-dimethyl-4-pyrimidylimino)-3//-l,2,4-thiadiazolo[4,3-c]py-rimidine (307) gave no rearranged products. Thus, it afforded 308 with HCI, whereas attempted rearrangement in NaOH gave a product which corre-... 

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). 

Three methods were reported to obtain the title compounds. The first was based on a reaction sequence starting from 5,6-diamino-4-thiouracil-sodium salt, alkylation with 1,2-dibromoethane to 7,8-diamino-2,3-dihydro-5//-thiazolo-[3,2-c]pyrimidine (135) and fusion with urea or thiourea under formation of a third ring to the respective 7,8-dihydrothiazolo[2,3-/]purine-2,5(l//,3//)-dione (136) and 2,3,7,8-tetrahydro-2-thioxothiazolo[2,3- ]purin-5(l//)-one (137) (92FES1315) (Scheme 37). 

Reaction of levoglucosenone with urea, thiourea, or J -cyano- or W-ni-troguanidine resulted in the formation of the pyrimidine systems 99 in a stereospecific manner [153,154], Its reaction with a-aminoazoles yielded azolo[l,5-a]pyrimidine systems fused with a carbohydrate fragment. The reaction occurs much more smoothly than in the case of other a,jS-unsaturated ketones. The reactions of levoglucosenone with /3-dicarbonyl compounds (dimedone, barbituric acid) in the presence of a base resulted in pyran ring closure [153,154]. 

Abdel-Mohsen in 2003 reported the formation of thiazolo-[3,2-a]-pyrimidine 102 (Scheme 45). Refluxing of thiourea with 5-chloro-aeetyl-8-hydroxyquinoline... 

Phenyl-3H-thiazol-2-yhdene)malononitrile 133, was obtained by cyclocondensation of l-phenyl-2-thiocyanatoethanone with malononitrile, on the reaction with thiourea or guanidine (Scheme 60) led to the formation of thiazolo[3,2-c]pyrimidine 134[86],... 

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