4-Thiazolidinones substitution

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. 

Trichloromethyl substituted thiazolidines have been prepared from chloral. Reaction of chloral with anilines afforded the corresponding imines which were then treated in situ with thioglycolic acid to give a series of 2-trichloromethyl substituted thiazolidinones <96HC227>. 

Scheme 6.219 Synthesis of benzothiazoles [391, 392], thiazolobenzimidazoles [370], and heteroaryl-substituted thiazolidinones [370],...

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>. 

Attempts to perform synthesis of 3-substituted thiazolidinones by the MCR of 2-aminoazoles with mercaptoacetic acid and aldehydes were described by Grasso et al. [164-166]. 

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). 

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... 

Kidwai, M., Kumar, P., Goel, Y. and Kumar, K., Microwave assisted synthesis of 5-methyl- 1,3,4-thiadiazol-2-ylthio/tetrazol-l-yl substituted pyrazoles, 2-azetidinones, 4-thiazolidinones, benzopyran-2-ones and 1,3,4-oxadiazoles, Indian. J. Chem., Sect. B, 1997, 36, 281. 

Some of the other scaffolds used to synthetize Kvl.5 channel inhibitors are prototypes of vicinally substituted heterocycles, such as the tetrazole 2f shown in Table 1. This series was developed to circumvent a metabolic liability of thiazolidinone derivatives previously identified as potent Kvl.5 blockers [54]. Some chemistry efforts have been directed toward novel structures that provide practical advantages in addition to Kvl.5 potency. This is the case of Kvl.5 inhibitors based on a diisopropyl amide scaffold [50]. 

The most widely used procedures for the preparation of 4-thiazolidinones describe the formation of the 3,4-bond via cyclization of an appropriately substituted acyclic compound which had been generally prepared from either thiourea or thioglycolic (mercaptoacetic) acid derivatives. Formation of... 

The simplest synthesis of pseudothiohydantoins (8) is by condensation of thiourea (6) with substituted a-chloroacetates (7)3 5 [Eq. (1)]. Synthons6 of 7, epoxyacids,7 a-chloroacetic anhydrides,8 and dialkyl acetylenedi-carboxylate,9 have been successfully substituted for 7. Symmetrical diaryl-thioureas (9), conveniently synthesized from the corresponding arylamine and carbon disulfide, react with a-haloacetic acid derivatives to give a single thiazolidinone 108,10,11 [Eq. (2)]. 

Symmetrical dialkylthioureas react with 7 to give a single product. Un-symmetrical substituted thioureas (11) have been condensed with 7 to afford two isomeric 2-imino-4-thiazolidinones (12a,b) however in most cases, a predominant isomer has been obtained. Structural configurations of 12 have been deduced by hydrolysis to the corresponding diones (13a,b),... 

Condensation of monochloroacetic acid with an arylthiourethan (41) in glacial acetic acid leads to 42 [Eq. (12)].76 With alkylthiourethans, reaction temperatures must be maintained at 160°-170°.77 Simultaneous reaction of the starting materials or 42 with aromatic aldehydes affords high yields of the 5-arylidene derivatives.76 Similarly, arylamides of arylsulfonylcyano-thioacetic acids condense with a-halocarboxy compounds to afford 2-substituted 4-thiazolidinones.78... 

Aryl-3-JV-phenylimino-l,2-dithiol (78) condenses with a ketene to give 79 [Eq. (23)] which, when wanned, reverts to 78.98 Substituted ketenes with 78 give the corresponding 5-substituted 79. The related 5-phenylamino-3-imino-l,2,4-dithiazoline, when heated in acetic anhydride, rearranges to afford 2-acetylimino-3-phenyl-4-thiazolidinone (95%).99... 

Pyridylethyl derivatives of 2 are formed by reaction of a- or y-vinyl-pyridine with 2.107 Treatment of 1 or 2, as well as the 5-arylidene derivatives, with acrylonitrile in the presence of pyridine results in formation of 84 by cyanoethylation on the ring nitrogen (Scheme 2) however, cyanoethyla-tion of 5-aryl-2-iminothiazolidinones involves the exocyclic nitrogen.108 Aminoalkylation (Mannich reaction) of 2 or 2-aryl-4-thiazolidinones with formaldehyde and amines in warm alcoholic solvents affords the desired 3-alkylated product 85 (Scheme 2),109,110 whereas 3-aryl-2-iminothiazoli-dinones react with substituted anilines and aliphatic amines and formaldehyde to give the 2-arylaminomethyl derivatives 86 [Eq. (25)].111... 

Phenylazo-2-thiazolidinone-4-thione (107), when treated with aniline and sodium acetate in acetic acid under reflux for 20 minutes, is converted into 108 in 54% yield [Eq. (34)], whereas, with aniline in methanol at 60° for 1.5 hours, it is transformed by 4-substitution to 109.144 (Hydrazone tautomers, as shown, are likely for 107 -109.)... 

Phenylhydrazono-4-thiazolidinones (124) and their 5-substituted derivatives are cyclized upon treatment with formaldehyde or aromatic aldehydes to give the bicyclic structure 125.169 5-Arylidene derivatives of 126 have been cyclized to 127 by initial treatment with chloroacetic acid, followed by hot acetic anhydride or concentrated sulfuric acid.170... 

Numerous studies of the infrared spectral data have been reported, especially in connection with the problem of the tautomeric equilibria of substituted 4-thiazolidinones. Particular references to substituted derivatives of 2109-121-178-179 and 312-126-132-179-180 are of interest. 

From the pKa values, the following sequence of 2-substituted 4-thiazolidinones with respect to the degree of acidity are 5 > 2 > 3.186 The opening of the thiazolidinone ring leads to an increase in acidity, but does not affect the activity sequence of the substituents.186 The acidity of a series of substituted 5-benzylidene-2,4-thiazoIidinediones has been investigated the entropy, enthalpy, and free energy of ionization have been calculated.187 Potentiometric determination of the tautomeric equilibrium constants of various 4-thiazolidinones has been reported.188... 

The N3-unsubstituted thiazolidinones are usually solids and often melt with decomposition, but substitution at this position lowers the melting point. The thiazolidinones that do not carry N3-aryl or higher alkyl substitution are partially soluble in water and can be recrystallized from water. Thiazolidinones undergo a limited number of chemical transformations as shown in Scheme 9. The methylene carbon atom at the 5-position of thiazolidinone possesses nucleophilic activity and can attack an electrophilic center. Most frequently the reaction occurs in the presence of... 

The hybrid molecules, comprised of sydnones and other heterocyclic compounds, constitute one of the more promising approaches for the design of bioactive compounds. 3-Aryl-4-formylsydnones (22) are attractive starting compounds for several 4-heterocycle-substituted sydnones, such as thiazo-lidinone (23) and thiazoline (24, 25) [14,15], imidazoles (26) [16], thiadia-zolines (27), thiadiazoles (28) [17], and indoles (29) [18]. Some sydnonyl-substituted thiazolidinone (23) and thiazoline (30) derivatives exhibited a potent l,l-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, comparable to that of vitamin E [14,15]. 

Yadav AK, Kumar M, Yadav T, Jain R (2009) An ionic liquid mediated one-pot synthesis of substituted thiazolidinones and benzimidazoles. Tetrahedron Lett 50 5031-5034... 

Oxidation of 5-substituted-2-thioxo-4-thiazolidinones (201) with bromine in acetic acid yield 2,4-thiazolidinediones (202) as shown in Equation (34) <9iBa750>. 

Naismith, R.E. Lee, Novel Inhibitors of an emerging target in Mycobacterium tuberculosis substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis, Bioorg. Med. Chem. Lett. 

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