S-Methyl 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... 

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]. 

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). 

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... 

Alkylation of the tetrahydropyridine, 52 (obtained by reaction of a suitable protected derivative of 4-piperidone followed by dehydration and deprotection), with chloroacetonitrile affords 53, Reduction of the cyano group gives the diamine (54). Reaction of this intermediate with the S-methyl ether of thiourea affords guancycline (55). 

As we have had occasion to note more than a few times previously, the guanidine function forms the basis of a family of hypotensive agents active by reason of their activity as blockers of the peripheral sympathetic system. Condensation of tetra-hydroisoquinoline with the S-methyl ether of thiourea affords the antihypertensive drug debrisoquin (135). ... 

N-(2,6-dichiorophenyl)thiourea (MP 149°C) was prepared in customary manner from 2,6-dichloroaniline (Organic Synthesis lil, 262-263) and ammonium thiocyanate. 16.0 g of this thiourea derivative were refiuxed for 2 A hours together with 16 g of methyl iodide in 150 cc of methanol. Thereafter, the methanol was evaporated out of the reaction mixture in vacuo, leaving as a residue 22 g of N-(2,6-dichlorophenyl)-S-methyl-isothiouronium hydroiodide of the formuia... 

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. 

Selective S-methylation of /V-(trimethylsilylmethyl)thioureas with methyl triflate proceeds smoothly to give the corresponding Af-(trimethylsilylmethyl)iminium triflates in almost quantitative yields.245... 

Fig. 6.21. Electrochromatographic separation of benzene derivatives on monolithic capillary column prepared by UV initiated polymerization. Conditions capillary column, 100 pm i.d. x 25 cm active length stationary phase poly(butyl methacrylate-co-ethylene dimethaciylate) with 0.3 wt. % 2-acrylamido-2-methyl-l-propanesulfonic acid pore size, 296 nm mobile phase, 75 25 vol./vol mixture of acetonitrile and 5 mmol/L phosphate buffer pH 7 UV detection at 215 nm 25 kV pressure in vials, 0.2 MPa injection, 5 kV for 3 s. Peaks thiourea (1), benzyl alcohol (2), benzaldehyde (3), benzene (4), toluene (5), ethylbenzene (6), propylbenzene (7), butylbenzene (8), and amylbenzene (9).

Demeton-s-methyl sulphon phosphoro organic, phosphoro thioate Desmedipham carbamate Desmetryn heterocyclic nitrogen, triazine Diafenthiuron thiourea... 

E. Reaction of Active Methyl and Methylene Compounds with Urea Acetals, S-Alkylated Thioureas and Carbodiimides... 

The RNAse model compound of Hamilton was constructed in a few steps (Scheme 15) [30]. Benzoyl isothiocyanate was allowed to react with diamine 59 to yield bis(thiourea) 61 after deprotection. S-methylation activated the urea moieties for guanidine formation with Af,A -dimethyl-ethy-lenediamine 62 to reach the desired compound 53. 

A, A( -Dimethylthiourea also produced 8-thioxopurines at lower temperatures than thiourea but the reaction may be complicated by S-methylation especially at higher temperatures as in the formation of 8-methylthiotheophylline (Scheme 95) (65AF10). 

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