Synthesis thiazolidinones

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... 

Babaogln K, Page MA, Jones VC, McNeil MR, Dong C, Naismith JH, Lee RE. Novel inhibitors of an emerging target in Mycobacterium tuberculosis, snbsti-tnted thiazolidinones as inhibitors of dTDP-rhamnose synthesis. Bioorg Med Chem Lett 2003 13 3227-30. 

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

Optically active 2-oxazolidinones and 2-thiazolidinones are versatile compounds as chiral auxiliaries. 5a b (4R,5S)-4,5-Diphenyl-2-oxazolidinone has been used for the synthesis of optically active amines6 because of its high stereoselectivity and easy deprotection by hydrogenolysis after the reaction. Compared with several preparations73-0 of (4R,5S)-4,5-diphenyl-2-oxazolidinone reported so far, this method,... 

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]. 

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. 

Examples of the synthesis of fused-ring azetidines by ring closure onto a preformed azetidine are uncommon, in contrast to approaches used for the preparation of fused ring azetidinones (see Sections 5.12.3, 5.11.4.4 and 5.10.4.3). The l,3-diazabicyclo[3.2.0]hep-tane derivative (48) was prepared (72JOC516) by cyclization with DCC of the carbamoyl-azetidine followed by thermal rearrangement of the intermediate thiazolidinone (Scheme 6). 

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. 

A recent paper276 has shown that some halocyclizations involving sulfur functionalities other than thiols (e.g. thiazolidinones) may involve initial reaction at sulfur to generate a sulfenyl halide which cy-clizes via attack of the electrophilic sulfur. This type of reaction would be an alternative to the nucleophilic heterocyclization mechanism previously proposed for a synthesis of a biotin intermediate from a vinylthiazolidine. P 277... 

Where possible, it is usually preferable to have the activated species (e.g., the active ester) in solution and the substrate (e.g., the amine component) on the solid phase. If the case requires an inverted situation, as for the synthesis of a thiazolidinone library (see Fig. 13),41 identification of the best reaction conditions may be more challenging, considering the relative scarcity of literature examples. 

A number of other solid-phase chemistries have been described for the generation of combinatorial libraries. This includes the synthesis of urea-linked diamines [51], bisamide phenols [52,53], polyphenols [54], thiazolidinones [55,56], thiazolines [57], hydantoins [58], and diaminoalcohols [59,60], Readers interested in more details of these libraries are referred to the section on small molecule libraries. 

Holmes CP, Chinn JP, Look GC, Gordon EM, Gallop MA, Strategies for combinatorial organic synthesis solution and polymer-supported synthesis of 4-thiazolidinones and 4-metathiazanones derived from amino acids, J. Org. Chem., 60 7328-7333, 1995. 

Structure-based design has been effectively utilized in synthesis of inhibitors of non-proteolytic enzymes. Inhibitors of MurB, an essential bacterial enzyme required for biosynthesis of peptidoglycan, were identified using the X-ray structure of the enzyme for library design. Thiazolidinone inhibitors (8) thus identified are the first examples of small molecule inhibitors of MurB. 

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)]. 

A convenient synthesis [Eq. (13)] of 2-ary lidenehydrazono-4-thia-zolidinone (43) from ethyl thiocyanoacetate (44), arylideneazines (45), and hydrazine hydrate (46) has been reported.79 Presumably, the reaction proceeds via the intermediary hydrazone, which condenses with 44 to give 43. Subsequently, condensation of 43 with the aromatic aldehyde, generated in situ from disproportionation of the azine with hydrazine, affords the 5-arylidene derivative. The reaction of 44 with ammonium acetate and an aromatic aldehyde gives 5-arylidene-2-imino-4-thiazolidinones.80... 

Condensed heterocyclo[n,m-n, b, or cjquinazolines. 52, I Condensed 4-thiazolidinones, 49, I Condensed thiophene systems, tetra- and pentacyclic, 32, 127 Condensed 1,2,4-triazines I. Fused to heterocycles with three-, four-, and five-membered rings, 59, 39 Condensed l,2,4-triazolo[3,4-z) heterocycles, synthesis, 49, 277 Conformational equilibria in nitrogen-containing saturated six-membered rings, 36, I... 

A carbodiimide (DCC) mediated synthesis of 4-thiazolidinones 547 using amines, aldehydes and mercaptoacetic acid affords yields of 80-95... 

Fahmy AM, Hassan KM, Khalaf AA, Ahmed RA (1987) Synthesis of some new P-lactams, 4-thiazolidinones and pyrazolines. Indian J Chem Sect B 26 884-887 Muller TJJ, Braun R, Ansorge M (2000) A novel three component one-pot pyrimidine synthesis based upon a coupling-isomerization sequence. Org Lett 2 1967-1970 Braun RU, Zeitler K, Muller TJJ (2000) A novel 1,5-benzoheteroazepine synthesis via a one-pot coupling-isomerization-cyclocondensation sequence. Org Lett 2 4181-4184 Braun RU, Muller TJJ (2004) One-pot syntheses of dihydro benzo[b][l, 4]thiazepines and -diazepines via coupling-isomerization-cyclocondensation sequences. Tetrahedron 60 9463-9469... 

Mahler and co-workers [140] reported a tandem procedure for the synthesis of 2-hydrazolyl-4-thiazolidinones 103 from a three-component reaction of an aldehyde, a thiosemicarbazide and maleic anhydride, efficiently assisted by microwave irradiation in a solvent mixture of toluene/DMF (1 1). Short reaction times and high product yields were obtained as compared to conventional heating. This process could be generally applied for aromatic as well as for aliphatic aldehydes, although for aliphatic aldehydes a slightly lower temperature of 100°C should be used (Scheme 80). 

Saiz C, Pizzo C, Manta E et al (2009) Microwave-assisted tandem reactions for the synthesis of 2-hydrazolyl-4-thiazolidinones. Tetrahedron Lett 50 901-904... 

Recently, Holmes et al. reported the solution and polymer-supported synthesis of 4-thiazolidinones and 4-metathiaznones derived from amino acids (Scheme 7) [29]. A three-component condensation of an amino ester or resin-bound amino acid (glycine, alanine, /1-alanine, phenylalanine, and valine). 

---