N-Monosubstituted Thioureas

Allylthiourea condensed with a-halocarbonyl compounds gives the corresponding 2-allylaminothiazoles (53, 91, 262, 557, 565, 586, 588, 621, 655, 800) (Table 11-16). 

Various 4-, 5-, or 4,5-disubstituted 2-aryIamino thiazoles (124), R, = QH4R with R = 0-, m-, or p-Me, HO C, Cl, Br, H N, NHAc, NR2, OH, OR, or OjN, were obtained by condensing the corresponding N-arylthiourea with chloroacetone (81, 86, 423), dichloroacetone (510, 618), phenacyichloride or its p-substituted methyl, f-butyl, n-dodecyl or undecyl (653), or 2-chlorocyclohexanone (653) (Method A) or with 2-butanone (423), acetophenone or its p-substituted derivatives (399, 439), ethyl acetate (400), ethyl acetyl propionate (621), a- or 3-unsaturated ketones (691), benzylidene acetone, furfurylidene acetone, and mesityl oxide in the presence of Btj or Ij as condensing agent (Method B) (Table 11-17). 

2-Sulfonamido, 2-phthalimidomethyl (650) and 2-(JV-4-maleylsul-phanilamido)thiazoles (710), and N-thiazolylphosphoramido thiazoles were prepared similarly (790). 

TABLE 11.16, 2-ALLYLAMINOTHTAZOLES FROM ALLYLTHIOUREA AND a-HALOCARBONYT. COMPOUNDS 

General Synthetic Methods for Thiazole and Thiazolium Salts 

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N-monosubstituted thioureas also react with a-haJoacids or esters to give stable compounds of type 126, in which R is aryl or acyl. When R is alkyl such as an allyl group (85), isomer 125 is formed (Scheme 60). 

Michael reaction, A1<9) octalone, 45, 82 N Mono- and N,N disubstitdted UREAS AND THIOUREAS 45, 69 N Monosubstituted thioureas from primary amines and silicon tetra-lsothiocyanate, 45, 69 N Monosubstituted ureas from primary amines and silicon tetraisocyan-ate, 46, 69... 

Reactions of N-monosubstituted thioureas 146 and a-haloacyl halides 147, in the presence of triethylamine, give mesoionic thiazol-3-ium-4-olates 148 (Scheme 54) <1996M1251>. 

Reactions with N-substituted Thiourea 3.1.2.1. N-monosubstituted thioureas... 

The cyclization of N-substituted thioureas (123) with halocarbonyl compounds gives 2-monosubstituted aminothiazoles (124) (Scheme 58)... 

With R] different from R2 two isomeric compounds (138 and 139) are possible, depending on the direction of ring closure (86). However, only one form is generally obtained. Finally, the trisubstituted thioureas such as N,N,N -trimethylthiourea react with chloroacetone to give a thiazolium salt, in a reaction identical to that of the N-monosubstituted thioamides (Scheme 67). 

As a corollary, N-monosubstituted and unsymmetrically /V-disubstituted derivatives are expected to exhibit (E)-(Z) geometrical isomerism. In the case of N,Nr-unsymmetrically disubstituted thioureas, up to four different configurational arrangements can be envisaged, the (E,E) isomer being generally absent because of steric repulsion between the nitrogen substituents (Fig. 3). 

The 2-monosubstituted or disubstituted aminothiazoles obtained reaction between Halo carbonyl and N-substituted thiourea compounds [38]. 

Several recent papers deal with the restricted C—N rotations in monosubstituted, NN -disubstituted, and NNN -trisubstituted thioureas, together with the conformational aspects involved. N-Alkyl-thioureas were found to exist both in the cis- and the trans-form, but N-arylthioureas appeared to exist solely in the intramolecularly hydrogen-bonded form (363). A similar form (364) was found to be predominant in l-alkyl-3-aryl- and 1,3-diaryl-thioureas, whereas both of the isomers (365) and (366), but not the sterically unfavourable form (367), were detectable in the case of l,3-dialkylthioureas. Reeves and his coworkers, by means of a total n.m.r, line-shape fitting, have evaluated the... 

Several recent papers deal with the restricted C—rotations in unsubstituted/" monosubstituted, NlsT-disubstituted, NN-disubsti-tuted, N,N,N -trisubstituted, " and tetrasubstituted " thioureas, together with the conformational aspects involved. The barriers to C—N rotation of thio- and seleno-urea were equal (AF = 12.8 kcal mol" ) and above that of urea (AF = 11,0 kcal mol" ). Restricted-rotation phenomena have been observed for substituted N-(tosylmethyl)thioureas, thiourea S-trioxides, " and 3-aryl-2-thiohydantoins. ... 

Agents that are oxidatively activated and inactivate the enzyme by covalently binding to it include (a) diverse sulfur compounds (e.g., carbon disulfide , parathion -, diethyldithiocarbamate , isothiocyanates , thioureas , thiophenes , tie-nilic acid - - , and mercaptosteroids , (b) halo-genated structures such as chloramphenicoF- , A-monosubstituted dichloroacetamides , and N-(2-p-nitrophenethyl)dichloroacetamide , (c) alkyl and aryl olefins and acetylenes such as... 

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