Thiourea pyrimidine ring

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]. 

The reduction of thiamine hydrochloride in neutral buffer is reported to involve a cleavage between the pyrimidine ring and the thiazolium ring and a ring opening of the latter further chemical steps lead to a substituted thiourea [285]. 

The pyrimidine rings of 970 were built on the 2-formyl-3-()8-D-ribofurano-syl)propanoate enol ether derivative 969 by reaction with urea, thiourea, or guanidine (79MI2, 79TL3669 83BCJ2700) (Scheme 279). 

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... 

Ambident nucleophiles, such as guanidine, thiourea, and urea attack 1,3-dimethyluracil first at the 6-position. After cleavage of the uracil ring and displacing ring closure, novel pyrimidines are formed extruding di-... 

When the amine used in the cyclization of a pyrimidine related to (28J) is replaced by thiourea, sulphur is incorporated in the newly formed ring [20S0]. Bromo and carbonyl functions may be annulated by reacting with a thioamide [2933]. A stronger base than sodium carbonate (p. 131) is sometimes preferred in the cyclization of a haloaldehyde [3267]. 

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). 

The protected 2-formyl-L-arabinal reacted with thiourea and cyanamide in the presence of sodium hydride to afford, via ring transformations, the 5- [ lR,2S-l,2-bis(benzyloxy)-3-hydroxypropyl]- 1,2-dihydropyrimidines. Similarly, treatment with 3-amino-2H-1,2,4-triazole yielded 6-[lR,2S-l,2-bis(benzyloxy)-3-hydroxypropyl][l,2,4]-triazolo[l,5-a]pyrimidine [151]. Reaction of 27 with 2-aminoimidazole and 2-aminobenzimidazole gave 96 and its bezo-analogues [64]. 

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]. 

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 ... 

Representatives of the l,2,4-thiadiazolo[3,2-b]thiazole (101), 1,2,4-thia-diazolo[2,3-a]pyridine (102), and l,2,4-thiadiazolo[2,3-a]pyrimidine (103) ring-system are accessible in high yield by the action of bromine in chloroform on the appropriate heterocyclic thiourea, e.g. (100). ... 

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