Synthesis of new thiazolidine and imidazolidine derivatives of pharmacological interest

Abstract

The hitherto unknown 5‐(2‐aryl‐2‐oxoethyl)‐4‐oxo‐1,3‐thiazolidines 1a‐l have been synthesized viacycloaddition process between thiourea and/or its derivatives with 3‐aroylpropenoic acids. 1H NMR spectra revealed the presence of 1a‐c as a tautmeric mixture. The presence of the thiazoline tautmers (1a‐c)′ was confirmed by methylating the tautmeric mixture, to the respective methylated derivatives 2‐N‐methylanilino‐5‐(2‐aryl‐2‐oxoethyl)‐4‐oxo‐1,3‐thiazolines2a‐c and 1g‐i. Acidic treatment of 1 provided the respective 2‐oxo homologues 3a‐i. When 1a‐d, k were refluxed with DMF, molecular rearrangement was achieved, providing the 4‐oxo‐2‐thioxoimidazolidine isomers4a‐d, k. Bromination of 4a and 4d in hot acetic acid afforded the respective (E,Z)‐5‐benzoylmethylene derivatives 5a,d which were prepared authentically. Thiation of 1a‐c and 4a‐c gave 5‐aryl‐2,3‐dihydro‐2‐phenyliminothieno[2,3‐d]thiazoles 6a‐cand 1‐phenyl‐5‐aryl‐2,3‐dihydro‐2‐thioxothieno[2,3‐d]imidazoles 7a‐c, respectively. The proposed structures have been confirmed by elemental analysis and spectroscopic data. The selected products showed different antimicrobial effect.

Advancements in synthesis of pharmacologically active imidazolidin‐4‐ones and stereochemistry of their Reactions with some Reagents

“…Imidazolidin‐4‐ones are characterized by different biological activities. Some of these activities are antimicrobial, antitumor, antifungal and anti‐parasitic . There are other pharmacological applications have been cited in reviews .…”

“…There are other pharmacological applications have been cited in reviews . The imidazolidin‐4‐ones 2 are antimicrobial active derivatives have been prepared from (3 H )/3‐phenyl‐5‐(2‐oxo‐2‐arylethyl)‐2‐phenylimino‐1,3‐thiazolidin‐4‐ones 1a‐f , by reflux in dimethyl formamide. The stability of the transition state has been manifested by the presence of the aryl group at C‐2; thus, the 2‐imino‐ 1e gave poor yield of 2e .…”

“…The imidazolidin‐4‐ones 2 are antimicrobial active derivatives have been prepared from (3 H )/3‐phenyl‐5‐(2‐oxo‐2‐arylethyl)‐2‐phenylimino‐1,3‐thiazolidin‐4‐ones 1a‐f , by reflux in dimethyl formamide. The stability of the transition state has been manifested by the presence of the aryl group at C‐2; thus, the 2‐imino‐ 1e gave poor yield of 2e . Herein, we explored the preparation of 2 , with a slight modification in the reaction conditions and investigated their behavior towards some reagents.…”

Thiazol-4-one derivatives from the reaction of monosubstituted thioureas with maleimides: structures and factors determining the selectivity and tautomeric equilibrium in solution

“…This behavior has not been explained and there is lack of more recent information on the regioselectivity of this reaction. On the other hand, the addition of monosubstituted thioureas to maleic anhydride [12–16] or its open-chain derivatives [17–18] leads to thiazolidines with the parent thiourea’s substituent in the exocyclic position.…”

“…This phenomenon was first detected by UV spectroscopy [19] and believed to be caused by a proton transfer between nitrogen atoms (amino–imino tautomerism), however, contradictory information on the equilibrium ratio of tautomers exist [15,18,20–23]. ( E / Z )-Isomerization of the exocyclic C=N bond of the single imino form was suggested as the cause for the dynamic effect as well [24–25].…”