1-Methyl- 1 - -2-thiourea

Primary synthesis has limited application in making pyrimidine-carboxylic acids or even their esters. However, some pyrimidine-4(and 5)-carboxylic acids can be effectively so made. For example, bromomucic acid (785) reacts as an aidehydo ketone with S-methyl-thiourea to give 5-bromo-2-methylthiopyrimidine-4-carboxylic acid (786) directly (53JCS3129) while the Whitehead synthesis (Section 2.13.3.1.2<7) can give, for instance, 3-methylcytosine-5-carboxylic acid (787) (55MI21300). 

S-Methyl thiourea Chloroformic acid methyl ester 3,4-Diamino-diphenyl-thioether... 

Structure is 9 kcal/mol higher than III, the dimethyl-methyl-thiourea prefers an coordination mode which can be rationahsed to other thioureas since it involves the S lone pair. Thioureas and ureas have therefore very distinct coordination modes. 

An analogous sequence leads to the anthelmintic agent, etibendazole (50). Reaction of the benzophenone 47, which can be obtained by acylation of g-nitroaniline with p-fluorobenzoyl chloride, with ethylene glycol leads to acetal 48. Sequential reduction of the nitro group and cyclization of the resulting diamine (49) with N,N-dicarbomethoxy-S-methyl thiourea gives the benzimidazole etibendazole (50) fl6]. 

A 1 1 complex is possible because both ends of the N-methyl thiourea guest bind centrosymmetrically to separate host molecules. This results in long chains of alternating host/guest molecules. 

Methyl thiourea Methylamine + carbon disulfide - CH3NHCSSNH4 Pb (N03)2 - methyl isothiocyanate + NH3 - methylthiourea... 

Condensation reaction between active methyl and methylene compounds and S-alkylated thioureas provides another useful synthetic pathway to the 1,1-enediamines. Rajappa and coworkers20 reported that nitromethane condensed with S-methylated thioureas 72, prepared from the reaction of amines and methyl isothiocyanate followed by S-methylation, to form asymmetric nitro 1,1-enediamines 73 (Scheme 5). 

Mercaptoacetic Add 2-Mercaptobenzoic Acid Methane Methanol Methionine Methotrexate Methylene Blue A-Methyl Glycine 5-Methylindole Methyl Isocyanate Methylmalonic Add Methyl Methacrylate Methylmethane Sulfonate Methyl Thiocyanate A-Methyl Thiourea Methyl Urea Naphthalene Nicotinic Acid Ornithine Orotic Acid Oxalic Acid Oxindole Palmitic Acid Paraldehyde Pentobarbital Phenol... 

Using two moles of aminoacetic acid to each mole of carbon disulfide causes the reaction to follow a different path (S55). N,N -bis(carboxy-methyl) thiourea (CLXXXIV) is formed which, on refluxing with hydrochloric acid, undergoes ring closure to the 1- carboxymethyl)imida-zolidin-5-one-2-thione (CLXXXV). 

The oxidation of N-ethoxycarbonylthiourea by bromine in boiling chloroform yields a complex mixture, separable chromatographically into N-ethoxycarbonylurea (8%), 3,5-bis(ethoxycarbonimino)-l,2,4-dithiazolidine (29%) and three 1,2,4-thiadiazoles, viz, 52 (R1 = R2 = COOEt, 8%), its 2,5-bis(ethoxycarbonyl) isomer (2%), and 52 (R1 = H, R2 = COOEt, 3%). Other IV-alkoxycarbonylthioureas, as well as l-ethoxycarbonyl-3-methyl-thiourea, react analogously.67... 

The etherification of 4-mercaptoacetanilide with w-propyl bromide gives rise to the formation of 2-nitro-4 (propylthio) acetanilide with the elimination of one mole of HBr. The resulting product upon hydrolysis converts it to an amine, reduction with SnCl2 to a diamine, and finally interaction with S-methyl thiourea affords eyelization to yield carbamie aeid [5-(propylthio)-IH benzimidazol-2-amino]. This upon acetylation with methyl ehloroformate affords the offieial eompound albendazole. 

By heating together 4-ehloro-3-nitro benzophenone and ammonia at 125°C for 24 hours in the presence of sulfolane yields 4-amino-3-nitrobenzophenone. The resulting product on being treated with hydrochloric acid and hydrogenation with Pd-on-charcoal as a catalyst yields diaminobenzophenone hydrochloride. This on being treated with S-methyl thiourea in the presence of methyl chloroformate... 

---