Selectedly substituted imidazolidinethiones and thioimidazolines: syntheses, structure, chemical reactivity, and pharmacological properties

Selectedly substituted imidazolidinethiones and thioimidazolines were synthesized because of their close structural relationship to biotin and known CNS depressant agents. N-carbomethoxy-2-allylthioimidazoline and N-carbomethoxy-2-p-fluorobenzylthioimidazoline are both active methylene compounds. Treatment of these substrates with potassium tert.-butoxide did not lead to an intramolecular transfer of the carbomethoxy group. In each case, only the corresponding S-substituted thioimidazoline was isolated. An examination of the thermal reactivity of N-acetyl-2-allylthioimidazoline and N-carbomethoxy-2-allylthioimidazoline was undertaken. Thermolysis of N-acetyl-2-allylthioimidazoline (145[degrees]C, 72 hr) gave the N,N'-disubstituted isomer, while N-carbomethoxy-2-allylthioimidazoline (170[degrees]C, 72 hr) gave N-methyl-N'-allylimidazolidinethione and N-allylimidazolidinethione. Evidence for a [3,3]sigmatropic rearrangement in these reactions was gleaned from thermolysis of N-acetyl-2-crotylthioimidazoline (145[degrees]C, 17 hr). The only product isolated in this reaction was N-acetyl-N'-(3'-butenyl)-imidazolidinethione. The imidazolidinethiones and thioimidazolines synthesized were evaluated for their CNS depressant and anticonvulsant properties in mice. N-carbomethoxy-2-p-fluorobenzylthioimidazoline and N-acetyl-2-p-fluorobenzylthioimidazoline were the most active compounds, exhibiting strong anticonvulsant and CNS depressant effects.