Thioamide compounds

Synthesis from thioamides. Compounds prepared using thioamides include 4-(4-chlorophenyl)-2-[4-(hydroxy or acyl)phenyl] thiazol-5-ylacetic acids,2-(hydroxyphenyl)thiazole-4-carboxylic acids and derivatives, and substituted... 

From thioamides. Compounds prepared from thioamides include... 

Pressure-Tuning Raman Spectra of Diiodine Thioamide Compounds Models for Antithyroid Drug Activity... 

The pressure-tuning Raman spectra of five solid, diiodine heterocyclic thioamide compounds (mbztS)f (mbztS = N-methyl-2-mercaptobenzothiaz-ole) (1) [(mbztS)f]fIfi (2) (pySH)f (pySH = 2-mercaptopyridine) (3) [(pySH)(pyS] [If (4) (thpm)(Ifi or possibly [(thpm)IJ-v[If- (thpm = 2-mercapto-3,4,5,6-tertahydropyrimidine (5) have been measured for pressures up to 50 kbar using a diamond-anvil cell. Compounds 1, 4, and 5 undergo pressure-induced phase transitions at 35, 25, and 32 kbar. 

Raman spectroscopy continues to be an extremely useful probe for examining the structural features of diiodine [14, 15, 23] and interhalogen [24] thioamide compounds. In the pressure-tuning FT-Raman spectroscopic work reported here, structural phase transitions were detected for compounds 1, 4, and 5 at 35, 25, and 32 kbar, respectively. There was no evidence of any free I formation for any of the compounds examined under high pressures. The similarity of the FT-Raman spectra of the two pairs of compounds, 1, 2, 3, and 4, may be the result of them being closely related perturbed diiodine complexes [25]. In the case of compounds 3 and 4, it is also possible that a pressure-induced disproportionation of 3 may have occurred leading to the formation of 4, in a similar manner to the effect of pressure on [(bztzdtH) 12 (bztzdtH = benzothiazole-2-thione) [4]. Finally, the FT-Raman data show that 5 is best formulated as (thpm) ) rather than the ionic species [(thpm)IJ [l3] -... 

It has been tentatively suggested that one mechanism underlies the Willgerodt reaction and the Kindler modification of it. A labile intermediate is first formed which has a carbon—carbon bond in the side chain. The scheme is indicated below it postulates a series of steps involving the addition of ammonia or amine (R = H or alkyl), elimination of water, re addition and eUmination of ammonia or amine until the unsaturation appears at the end of the chain then an irreversible oxidation between sulphur and the nitrogen compound may occur to produce a thioamide. 

The preparation of these [4-hydroxy-THISs, (1), X = O] by cydization of a-carboxy-N-arylthiobenzimides (5) by treatment with acetic anhydride and triethylamine has been investigated in detail, and the structure has been revised for the compound previously described as 2.3-diphenyl-4-hydroxythiazolium hydroxide inner salt (1, X = 0, R = R = Ph, R = H) (Scheme 5) (3, 10). 4-Hydroxy-THlSs also arise by condensation of gem-dicyanoepoxides with thioamides (Scheme 6) (8). 

The O-S exchange method in presence of a-halogenated carbonyl compound is a very good one for thiazole compounds. The thioamide is prepared in situ by the action of amide upon phosphorus pentasulphide with solvent. The a-halogenated aldehyde reacts directly. But the O-Se exchange cannot be performed with a-halogenated carbonyl compounds because of the apparition of phosphoric acid. (Scheme 3), The C-Se bond is very sensitive to add pH. 

The cyclization of -halocarbonyl compounds is carried out with a great variety of reactants including thioamides, thioureas, their mono- or disubstituted derivatives, and salts and esters of monothiocar-bamic acid, leading to variously substituted thiazoles. 

The reaction of a thioamide with a-halocarbonyl compounds has been applied extensively, and many thiazoles (10) with alkyl, aryl, aralkyl, or heteroaryl functional groups at the three 2-, 4-, or 5-positions have been reported (Scheme 6). 

The cyclization of pentaacetyl-o-gluconic thioamide with chloroacetone and of pentaacetyl-D-galactonic acid thioamide with phenacyl bromide give the corresponding 4-substituted 2-(D-galactopentaacetoxypentyl)-thiazoles (27) (660) but in low yield (23 to 27%) (Scheme 13). The products may be deacetylated in the usual way. These compounds are interesting from a pharmacological point of view. 

The use of a reagent bearing a basic center or the addition of a base to the reaction mixture was recognized as necessary to prevent the acid-catalyzed elimination of the elements of water from the intermediates. Since the publication of this work, a number of similar intermediates have been isolated from thioamides and a-halogeno carbonyl compounds (608, 609, 619, 739, 754, 801), and as a result of kinetic studies, the exact mechanism of this reaction has been well established (739, 821). 

II. Thiazoles from a-Halocarbonyl Compounds and Derivatives 211 2. Reaction with N>Substituted Thioamides (ThiazoHum Salts)... 

N-Monosubstituted thioamides (96) have been cyclized with a-halocarbonyl compounds to give thiazolium salts (97) in excellent yields (89, 99. 102, 305, 722). 

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). 

But the reaction with aliphatic a-halocarbonyl compounds is usually complex, and a variety of compounds can be formed depending on the reactants and the reaction conditions. With chloroacetone in neutral medium (alcohol) the acyclic intermediate (144) analogous to those obtained with thiourea and thioamides was isolated (Scheme 70). 

In catalytic hydrogenation, a compound is reduced with molecular hydrogen in the presence of a catalyst. This reaction has found appHcations in many areas of chemistry including the preparation of amines. Nitro, nitroso, hydroxylamino, azoxy, azo, and hydrazo compounds can all be reduced to amines by catalytic hydrogenation under the right conditions. Nitriles, amides, thioamides, and oximes can also be hydrogenated to give amines (1). Some examples of these reactions foUow ... 

When hexafluoroacetone reacts with amides, urethanes [25], thioamides [26], amidines [27], sulfonamides [28, 29], sulfinainides [20], and f),0-dialkyl-amido-phosphates [27], the correspondmg semiamidals are formed m nearly quantitative yield The thermal stabihty of these adducts toward the retro reaction increases with the nucleophihcity of the ammo compound [5] Many polyfluonnated carbonyl compounds react likewise [22 22] On treatment of ureas [34], thioureas [34], thioamides [26], and C,77 diarylatmdmes [27, 25] first with hexa- fluoroacetone and then with dehydratmg agents, heterodienes are obtamed (equation 4)... 

Boger developed his pyridine synthesis out of a need to eonstruet a pentasubstituted pyridine in an approach to the formal total synthesis of antitumor antibiotic streptonigrin 44. The requisite triazine 48 was produeed by using this methodology in an iterative sense with two different aza-heteroeyeles. Reaetion of thioamidate 46 with tetrazine 47, in a eyeloaddition/eyeloreversion sequenee, afforded 1,2,4-triaziene 48. Exposure of enamine 49 to 48 resulted in the formation of 50. This compound was elaborated into a eompound that intereepted Kende s synthesis of 44. ... 

The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

The chemistry of thiazoles is interesting in view of their propensity for biological activity. Eor that reason thiazoloquinolines have also been a widely studied group of compounds. A preferred route to thiazoles exploits a-halogeno ketones in a reaction with thioamides to give the fused 2-substituted thiazole derivatives. 

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