Arylidene thiazolidinones

Diazacyclotridecane-2-thione (231) reacts with chloroacetic acid or ethyl chloroacetate to furnish thiazolo [3,2-a]-[l,3]diazocyclotridecane-3(2//)-one (232). Compound 231, on condensation with ethyl chloroacetate and aldehydes in the presence of pyridine and piperidine, yields arylidene-thiazolidinone (233) which is also obtained from 232 and aldehydes (83J1C970) (Scheme 56). No spectral data are recorded. 

The thione 247 reacts with chloroacetic acid and aldehydes in a mixture of acetic acid and acetic anhydride to give arylidene thiazolidinone (253) [86IJC(B)776] which can also be obtained by the reaction of aldehydes with acid 248 (R = R = H)(56JOC24 72MIl)orwiththiazolidinone249a (56JCS361). 

Mercapto pyrimidines 82 were synthesized from acetoacetanilide, dihydroxybenzaldehyde, and thiourea, which were readily alkylated with benzyl chloride to afford 2-benzylthio derivatives 83 (Scheme 32). 83 when reacted with different amines in acetic acid furnished 2-amino derivatives 84 (R = Ar), whereas upon reaction with hydrazine hydrate 83 afforded 2-hydrazinyl derivative 84 (R = NH2), which with different aldehydes gave hydrazones 85 (R = 2-furyl, 2-thienyl). Arylidene thiazolidinone 86 was obtained from 84 with carbon disulfide, monochloroacetic acid, and aryl aldehydes, while 84 with ethyl acetoacetate and different aromatic aldehydes provided pyrazoles 87 (Scheme 32) (10MI9). Such tetrasubstituted pyrimidines act as cyclin-dependent kinase (CDK2) inhibitors. 

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... 

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... 

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... 

The 5-arylidene derivatives (e.g.,96) react with Grignard reagents via 1,4-conjugate addition to the exocyclic double bond to afford 97 [Eq. (28)] heterocyclic ring opening does not occur under these conditions.121 126,134,138 Other nucleophiles, such as p-thiocresol and piperidine, add 1,4 to exocyclic double bonds to give the simple adducts 97 (R = SAr and NR 2, respectively). 134 5-Methyl-3-phenyl-2-phenylimino-4-thiazolidinone undergoes... 

Arylidene-3-phenyl-2,4-thiazolidinones (118) undergo ring cleavage (N,—C2 and C4—C5 bonds) with excess benzylamine to give equimolar amounts of 119 and 120 [Eq. (37)].166,167... 

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... 

Cyclization of the 4-phenylhydrazono derivatives of 2-thiazolidinone with formaldehyde or aromatic aldehydes gives 2-phenyl-2,3-dihydro-thiazolo[4,3-c]l,2,4-triazol-5-ones (131) [Eq. (39)] subsequent condensation with aldehydes affords the corresponding 7-arylidene derivatives.171... 

Thiones 123 react with chloroacetic acid in the presence of anhydrous sodium acetate in acetic acid and acetic anhydride to give a cyclized product for which structure 124 has been assigned (82MI1). The cyclized product could be isomeric structure 125. The same workers similarly obtained a product formulated as 126 from the reaction of the thione 123 (n = 6) with chloroacetic acid (8IM12). Compound 126 reacts with aromatic aldehyde to furnish the arylidene product 127 which is also obtained from the reaction of thione 123 (n = 6), chloroacetic acid, and aldehydes as well as from the condensation reaction of thiazolidinone 124 ( = 6)... 

Thiazolidine-derived enamines 155 led to thio-substi-tuted bicyclic 1,4-dihydropyridine derivatives 156 in good to excellent yields [65]. A 4CR using thiazolidinone-derived enamines 158 gave the arylidene-substituted products 159/160 (Scheme 13.39) [66]. 

H. Behbehani, H.M. Ibrahim, 4-Thiazolidinones in heterocyclic synthesis synthesis of novel enaminones, azolopyrimidines and 2-arylimin o-5-arylidene-4-thiazolidinones. Molecules 17 (2012) 6362 85. 

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