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K. Spalin´ska et al.
INTRODUCTION
Many thiosemicarbazide derivatives described in the chemical
literature produced evidence of the antibacterial, antimalarial,1
antituberculitic,3 as well as anticancer2 activity. The compounds ob-
tained from these heterocyclic systems appeared to be of varied
biological activity as well. The 1,3,4-thiadiazole system-containing
derivatives showed antitubercu-litic,4,5 antibacterial, antimycotic,6,7
and analgesic8 actions. The 1,2,4-triazolo system-con-taining com-
pounds appeared to be antimycotic,9 Alzheimer’s-disease retarding,10
and icterus-Type C-virus-inhibiting11 agents. Their influence over the
immunology of HIV-1 virus infections12 was proved as well. How-
ever, the 1,2,4-triazolo-1,3,4-thiadiazine deri-vatives were recognized
as antiparasitic13 substances. Thus, further syntheses and investiga-
tion of this group of compounds seems to be well founded. Syntheses of
the new thiosemicarbazide derivatives, as well as of amino-substituted
azol derivatives, are reported in this article.
RESULTS AND DISCUSSION
In continuation of our search for potentially antibacterial substances,
the new thiosemi-carbazides and the products of their cyclization re-
actions with carbon disulphide to 1,3,4-thiadiazole, 1,2,4-triazole, and
1,2,4-triazolo-1,3,4-thiadiazine derivatives were obtained.
The substrate for further syntheses was 4-methyl-4-phenyl-3-
thiosemicarbazide 1, obtained by carbon disulphide addition to N-
methylaniline, followed by methylphenylthio-carbaminoylsulphonyl-
acetic acid and thioacetic acid elimination by a hydrazine hydrate
action.14
The products of the carbon disulphide addition to compound 1 de-
pended upon the reaction conditions. At the elevated temperature, 5-
N-methyl-N-phenyl-1,3,4-thiadiazolo-2-thiol 2 was obtained, which on
a methyl iodide action gave its S-methyl derivative 3. At r.t., however,
dithioacid 4 was obtained. The reaction of compound 4 with hydrazine
resulted in a 4-amino-5-N-methyl-N-phenyl-1,2,4-triazolo-2-thiol 5 for-
mation. From compound 1, the dithiocarbazoic acid methyl ester 15 was
obtained as well, but an attempt at obtaining from this compound the
1,3,4-thiadiazole substituted with amine groups and then the morpho-
line derivative of this thiadiazole failed, only compound 2 was obtained
instead.
The action of corresponding amines on compound 1 produced 4-N-
substituted thiosemicarbazide derivatives (6–10). Three of them were
condensed with 5-nitrofuryl aldehyde, which gave the condensation
products (12–14).