Parkanyi, Cyril

Thiadiazoles can be considered as analogs of pyrimidines because of the well
known analogy between a -CH=CH- group in benzenoid hydrocarbons and bivalent
sulfur, -S-, in aromatic heterocycles. Therefore, 5-amino-2H-1 ,2,4-thiadiazole-3-one and
5-amino-3H-1 ,3,4-thiadiazole-2-one are the analogs of cytosine. In our first project, the
preparation of six thiadiazole nucleoside analogs is reported: 5-diacetylamino-1 ,2,4-
thiadiazol-3-one (1), 5-amino-2-(tetrahydrofuran-2-yl)-1 ,2,4-thiadiazol-3-one (2), 5-
amino-3-((2' -hydroxyethoxy)methyl)-1 ,3,4-thiadiazol-2-one (3), 5-amino-3-( 4' -hydroxy-
2' -hydroxyrnethyl-butyl)-1 ,3,4-thiadiazole-2-thione ( 4), (R)-5-am ino-3-(2' ,3' -
dihydroxypropyl)-1 ,3,4-thiadiazole-2-thione (5), and (S)-5-amino-3-(2' ,3 ' -
dihydroxypropyl )-1 ,3,4-thiadiazole-2-thione (6). (R)-5-amino-3-(2' ,3' -dihydroxypropyl)-1,3,4-thiadiazole-2-thione (5) and (S)-5-amino-3-(2' ,3' -dihydroxypropyl)-1 ,3,4-
thiadiazole-2-thione (6) are stereoisomers. Their racemic mixture 7 was also prepared and
tested. The synthesis, characterization, and properties of these new synthesized
thiadiazole derivatives are discussed. A dimerization of 5-amino-3H-1 ,3 ,4-thiadiazole-2-
thione (18) to produce di-(5-amino-1 ,3,4-thiadiazol-2-yl) disulfide (23) by sodium nitrite
with either acetic acid or stannic chloride is also reported. Preliminary results indicate
that 3 and 23 possess antimicrobial activity. In the second project, the synthesis of three series of bis-aminochloropyrimidine
derivatives with different types of linkers as potential DNA intercalators is described.
The first series are aminochloropyrimidines bridged by polyrnethylene chain linkers with
various lengths. The second series are bridged by polyether linkers to lower the
lipophilicity. The third series are bridged by linkers containing benzene rings to limit the
flexibility. The spectral data and other physical properties of the new compounds are
discussed. The preliminary screening results indicate that many new synthesized bisintercalators
are biologically active. The relationship between bioactivity and structure is
discussed as well.

The synthesis and characterization of a series of new 4(3H)-quinazolinones is being reported. The new 4(3H)-quinazolinones have either one or two chlorine atoms in the benzene ring and a thiazol-5-yl or 1,3,4-thiadiazol-5-yl substituent in position 3. The new compounds were synthesized in a two-step procedure described before for a different series of compounds. Substituted chloroanthranilic acids (or 3,5-dichloroanthranilic acid) and acetic anhydride yielded the intermediate 3,1-benzoxazin-4-ones which subsequently afforded the desired products by reaction with a substituted 2-aminothiazole or 2-amino-1,3,4-thiadiazole in the presence of dry pyridine. In addition to elemental analyses and melting points, the new compounds were characterized by their 1H and 13C nmr, ir, uv, and mass spectra. The new quinazoline derivatives are expected to be biologically active and will be tested for their potential anticancer and antiviral activity.

Polyphosphate esters have been synthesized from reaction of the pentaerythritol ester of phosphorochloridic acid with different diols--bisphenol A, 1,6-hexanediol, 1,3-bis(4-hydroxybutyl)-tetramethyldisiloxane and 5-iodo-2'-deoxyuridine. All products are medium to high molecular weight. The product from bisphenol A gives fibers from concentrated solution. The product from 1,3-bis(4-hydroxybutyl)-tetramethyldisiloxane acts as an adhesive. The products were made for potential flame retardant applications in the electronics industry. The characterizations by MS, NMR and FT-IR are in agreement with the proposed structures.

The photodegradation of benzimidazole-based fungicides: benomyl ({1- [(butylamino) carbonyl)-1H-benzimidazol-2-yl} carbamic acid methyl ester), thiabendazole (2-(4-thiazolyl)-1H-benzimidazole) and fuberidazole (2-(2-furyl)-1H-benzimidazole) by ultraviolet radiation has been studied. Benomyl in an organic solvent (chloroform) undergoes a rapid degradation even without any UV radiation; UV radiation and air agitation will increase the rate of the reaction. The degradation product was found to be methyl 2-benzimidazolecarbamate (MBC) in all cases. The degradation of thiabendazole and fuberidazole in methanol was also studied under different conditions but degradation was observed only under UV radiation and in the presence of oxygen, 7-8 Photodegradation products were found in the mixture after irradiation of thiabendazole but only 2 of them were separated from the mixture and identified. Benzimidazole-2-carboxamide and dimethyl oxalate were two of the final photodegradation products of thiabendazole in methanol. It is clear that the thiazole ring is the most vulnerable part of the molecule and suffers ring cleavage. No photodegradation products of fuberidazole were identified so far.

The photodegradation of bromacil (5-bromo-3-sec-butyl-6-methyluracil) and terbacil (5-chloro-3-tert-butyl-6-methyluracil) by ultraviolet radiation has been investigated. Irradiation of aerated aqueous solutions of the title compounds (25 ppm), led to fast degradation of both. The reactions were found to follow first order kinetics with rate constants 5.77x10^-1 hr^-1 in the case of bromacil and 8.45x10^-2 hr^-1 in the case of terbacil. Degradation in ethanol and cyclohexane was also studied, but the solutions were not analyzed for photoproducts. The photoreaction mixture of both the herbicides in water showed four peaks on GC, indicating four photoproducts. Loss of halogens from the heterocyclic ring has been observed as shown by the presence of Br- in the case of bromacil and Cl- in the case of terbacil in the photoreaction solution. 6-Methyluracil which was isolated from the aqueous fraction of the photoreaction mixture was the common photoproduct from both bromacil and terbacil. From the organic fractions 3-sec-butyl-5-acetyl-5-hydroxyhydantoin was identified in the case of bromacil and 3-tert-butyl-5-acetyl-5-hydroxyhydantoin in the case of terbacil. The other two photoproducts were left unidentified.

The photodegradation of propiconazole (1-{[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl}-1 H-1,2,4-triazole), a systemic fungicide, by ultraviolet radiation has been studied. After 12 hours of continuous irradiation, propiconazole undergoes degradation in aqueous solution. The process requires the presence of oxygen and continuous agitation. Similarly, propiconazole undergoes degradation in organic solvents as well (methanol, hexane).