New direction in the reaction of thiocarboxamides with N-substituted maleimides

Abstract

The reaction of both aliphatic and aromatic thioamide derivatives with N-substituted maleimides under various conditions leads to the formation of complex polycyclic systems [1,2]. No information is available on the reaction of N-arylmaleimides with heterocyclic thiocarboxamide derivatives.We have found that the reaction of 1-aminothiocarbonyl-3,5-diarylpyrazolines 1a-1d [2] with N-substituted maleimides upon heating for 10 min in acetic acid at reflux leads to N-aryl-2-[2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-oxo-4,5-dihydro-1,3-thiazol-5-yl]acetamides 2a-d in high yield. This reaction permits broad variation of the substituents R, R 1 , and R 2 in the pyrazolinothiazolone molecules 2, which allows us to synthesize large combinatorial libraries of such compounds. N N N H 2 S R R 1 N O O R 2 N N N S O NH O R 2 R R 1 AcOH 1a-d 2a-d He Hd Hf Ha Hb Hc 1 a R = R 1 = Ph, b R = 4-MeOC 6 H 4 , R 1 = 4-MeC 6 H 4 , c R = 4-FC 6 H 4 , R 1 = 3-ClC 6 H 4 , d R = 2-C 4 H 3 S, R 1 = Ph; 2 a R = R 1 = R 2 = Ph, b R = 4-MeOC 6 H 4 , R 1 = 4-MeC 6 H 4 , R 2 = 4-F, 3-ClC 6 H 3 , c R = R 2 = 4-FC 6 H 4 , R 1 = 3-ClC 6 H 4 , d R = 2-C 4 H 3 S, R 1 = Ph, R 2 = 3-MeOC 6 H 4The structure of products 2a-d was indicated by 1 H and 13 C NMR spectroscopy and mass spectrometry. The 1 H and 13 C NMR spectra were taken on a Varian Mercury VX-200 spectrometer at 200 and 50 MHz, respectively, in CDCl 3 with TMS as the internal standard. The IR spectra were taken on a Perkin Elmer One FTIR spectrometer for KBr pellets. The electron impact mass spectra were taken on a Varian 1200L mass spectrometer at 70 eV.

Recyclization Reactions of N-Arylmaleimides with Polynucleophilic Compounds*

“…The splitting pattern, chemical shifts, and coupling constants between methylеne and methine protons matched the literature data for thiazolinones, obtained in N-arylmaleimide reactions with derivatives of thiourea. The structure of compounds was also supported by 13 С NMR spectral data [14][15][16] The specific involvement of thiourea fragment in the reaction was confirmed by the presence of molecular ion peak with m/z 84 in the mass spectra of compounds 3а-е, corresponding to dicyandiamide molecule. Decomposition to this compound was possible only for thiazolinones.…”

Synthesis and Anticancer and Antiviral Activities of New 2‐Pyrazoline‐Substituted 4‐Thiazolidinones

“…The target 2‐[5‐aryl‐3‐phenyl‐4,5‐dihydropyrazol‐1‐yl]‐5‐methylthiazol‐4‐ones 2a and 2b were synthesized by reacting mentioned binucleophiles with 2‐bromopropionic acid in the presence of fused sodium acetate in refluxing acetic acid. Reaction of 3‐phenyl‐5‐aryl‐1‐thiocarbamoyl‐2‐pyrazolines with maleic anhydride, N ‐arylmaleimides, and aroylacrylic acids [22, 23] resulted in the formation of the corresponding compounds 3a and 3b , 4a , 4b , 4c , and 5a , 5b , 5c , 5d , respectively.…”

“…The synthesis of 4‐thiazolidinone‐pyrazoline conjugates can be achieved by [2+3]‐cyclization of pyrazoline‐1‐carbothioic acid amides with equivalents of dielectrophilic synthon [C 2 ] 2+ [1]. Following literature data, only the derivatives of α‐halocarboxylic acids, phenacyl bromides, and N ‐arylmaleimides [18, 21, 22, 23] have been used in the reactions with mentioned compounds. Therefore, we tried to enlarge a scope of using of 1‐thiocarbamoyl pyrazoline derivatives as N , S ‐binucleophiles in [2+3]‐cyclization.…”

Synthetic approaches, structure activity relationship and biological applications for pharmacologically attractive pyrazole/pyrazoline–thiazolidine-based hybrids

“…2), synthesized via the [2þ3]cyclocondensation of 4,5-dihydropyrazole-1-carbothioamides 1.1 as S,N-binucleophiles in reactions with equivalents of dielectrophilic synthon [C2] 2þ , allowed to identify compounds with antimicrobial [23e28], antiviral [29,30], anti-inflammatory [31], antitumor [32e35] and insecticidal [36] activities. For synthesis of target derivatives a-halogenocarboxylic acids [31,33] and their ethyl esters [23e29, 35,36], maleic anhydride [30], maleimides [30,38], b-aroylacrylic acids [30], dimethyl acetylenedicarboxylate [37], bromoacetophenones [23,24,28,29,35] and ethyl 4chloroacetoacetate [35] were used as equivalents of dielectrophilic synthon [C2] 2þ .…”