2-thiazolidinone

Many examples of imidazo[2,l-/7]thiazol-3(2//)-one (11), imidazo[5,l-i ]thiazol-3(2//)-one (14), and their partially (12,15) and completely saturated (13) derivatives are known. Interesting biological activities have been found. 

The easy ring-opening quality of hexafluoro-1,2-epoxypropane in the presence of a nucleophile has been used to accomplish the synthesis of imidazo[2,l-fe]thiazol-3(2//)-one. Thus, the sodium salt of 4,5-diphenylimidazolyl-2-thione (16, R = = Ph) reacts with hexafluoro- 

2-epoxypropane in acetonitrile to furnish 5,6-diphenyl-2-fluoro-2-triflu-oromethylimidazol2,l-fe]thiazol-3(2/y)-one (18f) in a one-step synthesis (78BCJ3091). 

Stephen and Wilson (26JCS2531 29M11) and Limar (59M11) claimed to have synthesized 5,6-dihydroimidazo[2,l-6]thiazol-3(2//)-one (35) by reacting 28 with ethyl chloroacetate in the presence of pyridine or anhydrous sodium acetate. The compound reported by Limar was not characterized and the work of Stephen and Wilson could not be repeated by Campaigne and Wani who could, however, synthesize 35 by reacting 28 with ethyl 

Under identical conditions, 31 is found to be stable, while 39 (R = H, X = Cl) is labile. This difference is probably due to the presence of the methyl on the imidazole ring. To test the effect of a methyl group present on the thiazole ring on the stability of bicyclic compound 45, the reaction of 28 with ethyl a-bromopropionate was carried out. Compound 46 was 

The only example of this system has been reported in a patent (83EGP156815). 5-Amino-1 -benzoyl/substituted benzoyl-4-ethoxycarbo-nylpyrazolyl-3-thiones (72) react with either ethyl 3-anilino or substituted anilinocrotonates in boiling ethanol in the presence of metallic sodium to give 2-(a-anilino/substituted anilino)ethyl-5-benzoyl/substituted ben- 

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Aminothiazole and derivatives have been reported in reactivity studies starting from 2-p-nitrophenylsulfenylaminothiazole (4) (32), 2-tritylaminothiazole (5) (33), 2-nitrothiazole (34,35), and 5-methyI-2-phenylimino-4-thiazolidinone (36) (Scheme 4). 

C3NS S — N — — Thiamine hydrochloride monohydrate rhodanine 2-imino-5-phenyl-4-thiazolidinone ... 

Aldehydes and ketones react with azolinones. The reaction between aldehydes and 2-phenyl-5-oxazolinone (131 Y = H), formed in situ from PhC0NHCH2C02H and AC2O, gives azlactones (131 Y = RCH). Similar reactions are given by 4-thiazolidinones, e.g. (132) gives (133) (79AHC(25)83), and 4-imidazolinones. In pyrazolin-5-ones the 4-position is sufficiently activated for condensation to occur with ketones in acidic media (Scheme 8) (66AH06)347). 

To a stirred solution of 20 g (0.1 mol) 2-carbethoxymethylene-3-methyl-4-thiazolidinone in 120 ml chloroform is added, dropwise, a solution of 5 ml (0.1 mol) bromine in 20 ml chloroform. The solvent is removed by distillation and the residue crystallized from methanol to yield 18 g (65%) of 2-carbethoxymethylene-3-methyl-5-bromo-4-thiazolidinone, MP 76°C. 

To a solution of 28 g (0.1 mol) 2-carbethoxymethylene-3-methyl-5-bromo-4-thiazolidinone prepared as described In 200 ml benzene Is added (0.2 mol) piperidine and the mixture is allowed to stand for 3 hours at 25°C. The resulting suspension is filtered to remove the precipitated piperidine hydrobromide and the filtrate is evaporated to dryness. The residue is taken up in ether, filtered and the filtrate saturated with dry hydrogen chloride to yield the hydrochloride salt of 2-carbethoxymethylene-3-methyl-5-piperidino-4-thiazolidinone, MP 158°C to 159°C. 

The rapid synthesis of 4-thiazolidinones by the MCR of an amine, aldehyde and mercaptoacetic acid has been developed under microwave-assisted conditions [73-75]. Irradiation of the three components in ethanol at 120 °C in the presence of molecular sieves [73] or in toluene at reflux under atmospheric conditions [74] in a single-mode microwave synthesizer gave the... 

Preparation of a 4-thiazolidinone Library Employing a Functional Ionic Liquid Support... 

Fig. 34 Preparation of a 4-thiazolidinone library using an ionic liquid support. Reagents and conditions a MW 100 °C, l-2h, open vessel b R"NH2, t-BuOK, MW 100-150°C, 10-20 min. R = H, Me, CH2COOH R = Pr, i-Pr, i-Bu, Bn, piperonyl, CH2CH(OMe)2, CH2CH CH2 R" = Pr, Bu, Bn, or cyclic derivatives as piperonyl, piperidine, pyrrolidine,...

Arylmethylene-2-thioxo-4-thiazolidinones (34) react with phosphonium ylides to give dihydrofuro[2,3-rl]thiazol-2(3 -ones (35) in refluxing ethyl acetate, while performing the reaction in refluxing toluene led to the pyrone derivative (36) both of these products result from an initial 1,4-addition to the exocyclic double bond <95T11411>. 

Scheme 7.91 Generation of a 4-thiazolidinone library utilizing grafted ionic liquids.

Thiolactic acid, m22 Thiomalic acid, m25 Thiosalicylic acid, ml8 Thiosinamine, a97 2-Thioxo-4-thiazolidinone, r7 Threonine, al85 Tiglic acid, ml69... 

More recently, 2-thioxo-4-thiazolidinones 415 were reported to undergo facile thiophilic addition of a-phosphonyl carbanions and subsequent lactamization to generate bicyclic thiazolo [2,3-A thiazole-3,5-diones 416 (Equation 189) <2004PS1307>. 

Arylamino-spiro(cyclohexane)-(l, 2)-4-thiazolidinones 289, on treatment with concentrated sulfuric acid, give thia-zolo[4,3- ][ 1,3,4]oxadiazoles 109 (Equation 38) <2004IJC(B)901, 1999IJC(B)1203>. 

Thiazolidinones 290 give substituted thiazolo[4,3-A [l,3,4]thiadiazoles 112, 113, and 291 after intramolecular cyclization mediated by concentrated sulfuric acid (Equation 39) (Table 51) <2001IJC(B)440, 2004IJC(B)901, 1996JCR(S)388>. 

Tetratellurium tetranitride, 4773 Thiazyl fluoride, 4306 Thiotrithiazyl chloride, 4033 Thiotrithiazyl nitrate, 4767 Thiotrithiazyl perchlorate, 4032 2-Thioxo-4-thiazolidinone, 1112... 

A one pot formation and purification of a 5-arylidine 4-thiazolidinone library has also been reported using polymer scavenging as the principle method of purification. An automated synthesizer was employed to make a parallel array of 4080 4-thiazolidinones, prepared simultaneously from a 3-component condensation of mercaptoacetic acid with an amine and a carbonyl compound. Further structural decoration was then introduced using the libraries from libraries principle where the core template was derivatized via an aldol reaction with a second carbonyl unit at the 5-methylene position (Scheme 2.57) [84]. After both synthetic steps. 

For instance, the treatment of 2-aminothiazole or 2-amino-1,3,4-thiadiazole with a equimolar amounts of appropriate (hetero)aromatic or aliphatic aldehydes in the presence of an excess of mercaptoacetic acid under refluxing in anhydrous benzene gave diverse 2-substituted 3-(2-thiazolyl)- and 3-[2-( 1,3,4-thiadiazolyl)]-4-thiazolidinones 115a or 115b, respectively (Scheme 54). 

To decrease the reaction time required for the conventional treatment (from 2 up to 48 h) and to improve the conversion level of the reaction, microwave irradiation was successfully applied for obtaining 4-thiazolidinones substituted with azole ring. Siddiqui et al. [174] reported the efficient microwave-assisted solid-supported approach for one-pot diastereoselective synthesis of some analogs of fungitoxic dibenzyles. 

Bazureau s group reported extensive work with TSILs for synthesis of various 4-thiazolidinones, 1,4-dihydropyridines, 3,4-dihydropyrimidin-2(lH)-ones and polyhydroquinones. They functionalized imidazole compounds with esters, which were then reacted with reagents to afford the target compound. They report that microwave dielectric heating is a useful aid to rapidly produce the desired product in high yields. 

Alkyl- and aryl-substituted furo[2,3- / thiazolidine derivatives 279, with potential biological activity, have been synthesized by the reaction of methoxycarbonylmethylenetriphenylphosphorane with 4-thiazolidinone derivatives... 

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