Synthesis of 2-Amino-5-Substituted-1 , 3 , 4-Thiadiazoles ( ATDA ) and Their Derivatives Using Conventional and Microwave Techniques *

A variety of 2-Amino-5-substituted -1,3,4-thiadiazoles (ATDA) were prepared by the reaction of thiosemicarbazide with different substituted carboxylic acids and phosphorous oxychloride as catalyst using conventional methods in comparison with the advantages of microwave techniques. The 5-(substituted-1,3,4-thiadiazol-2-yl) carbamates derivatives were prepared by refluxing these (ATDA) with ethyl chloroformates using pyridine as a base to neutralize the acid produced which gave higher yield than sodium carbonate. The structures of the products were supported by IR spectroscopy.


INTRODUCTION
Several procedures were reported for the synthesis of 2-aminothiadiazoles, in many of these methods a thiosemicarbazide was the starting material.Among the most important procedures described were the acylation of thiosemicarbazide to produce 1-acylthiosemicarbazide which then cyclized with a suitable dehydrating agent (Shmeiss et al., 2002).
The energy profile in a microwave-assisted this cyclization was directly absorbed by the reactant molecules (Ajay et al., 2001), and may be quite different from that in which the reaction mixture was heated conventionally by conduction/convection using concentrated sulfuric acid, phosphorous oxy chloride or phosphoric acid (Saied, 1983).
A number of methods for the synthesis of carbamates have been reported, the reactions of amines with alkyl chloroformates being the most common (Saied, 1983;Olofson, 1988).
As part of continuous program directed toward the studies with polyfunctionally substituted heterocycles (AL-Gwady et al., 2007), it was become of interest to investigate preparative routs to synthesize anticipated insecticidal active carbamate derivatives by the reactions of chloroformate with a variety of some 2-amino-5-substituted -1,3,4thiadiazoles (ATDA).These (ATDA) were synthesized by the reaction of thiosemicarbazide and substituted carboxylic acids using microwave irradiation with comparison with conventional method in which phosphorous oxychloride was used as catalyst.

EXPERIMENTAL
All melting points were determined on a Gallen Kamp and Electro thermal 1A9300 Digital-Series (1998) apparatus and were uncorrected.The IR-spectra were recorded on Perkin-Elmer 590B Spectrophotometer.
Microwave irradiation method (b): (Kidwai, 2001;Aly et al., 2006;AL-Gwady et al., 2007) The reaction mixture of (0.9 g ,0.01 mole) thiosemicarbazide and (0.01 mole) of the proper carboxylic acid (0.005 mole for 2,6-pyridine dicarboxylic acid) were mixed with a spatula for a few minute, placed in an opend conical flask in a domestic microwave oven (containing crucible of 2 gm magnesium sulfate) and irradiated for 5 min.(the reaction was monitored by TLC to indicate the disappearance of the starting material).The resulting mixture was cooled, added to 250ml of stirred ice-cold water, neutralized with 10% sodium carbonate solution and worked up as in method (a).
No (1.085 gm, 0.01 mole) of ethyl chloroformate was added drop-wise to a solution of 0.01 mole of proper amine in 15 ml pyridine (0.005 mole for amine 1h).The reaction mixture was left at room temperature for one hour with occasional shaking.It was then poured onto 100 ml ice water and the precipited carbamate was filtered, washed with water, dilute hydrochloric acid, then with water again and crystallized from aqueous ethanol.Physical data were listed in Table (2).(Petrow, 1959) (0.84 gm, 0.01 mole) of anhydrous sodium carbonate was added to a solution of 0.01 mole of the appropriate amine in 20 ml.absolute ethanol (0.005 mole for amine 1h)., then (1.085 gm, 0.01 mole) of ethyl chloroformate was added drop wise.

Method (b):
The reaction mixture was refluxed for three hours, cooled to room temperature and poured onto 100 ml ice water.The precipitated product was filtered, and worked up as in method(a).

RESULTS AND DISCUSSION
Scheme (1) summarizes the synthetic route followed for the preparation of the title compounds.
The disappearance of C=O stretching in IR spectra was good indication of conversion of acid to heterocyclic ring, in addition to the following frequencies: 3144-3157 Cm -1 due to NH stretching, 1621-1628 Cm -1 for C=N stretching and this came in agreement to the published data (Hipler, 2002), and 618-625 Cm -1 for C-S ring stretching, Table (1).
In method (b) and to avoid the difficulty in processing (handling pollutant phosphorous oxychloride), to shorte the reaction time and to increase the yield (Kidwai, 2001;Aly et al., 2006), equimolar amounts of thiosemicarbazide and the appropriate acid were mixed together with 1% magnesium sulfate (as an additional microwave energy absorbant, the level of microwave energy required was reducedpresumably because of the attainment of higher efficiency of microwave energy absorption by the reaction mixture.), and the reaction mixture was irradiated in an open vessel in a domestic microwave oven for 5 minutes (Wilson,1971;Chaaban, 1984;Kidwai, 2001).The yield of these experiments ranged between 60% and 94%, Table (1  It was worthy to mention that a double cyclization occurred in case of 2,6-pyridine dicarboxylic acid to give compound 1h,while steric effect prevent that to occurre in 2,3pyridine dicarboxylic acid. Ethyl-N-(5-substituted-1,3,4-thiadiazol-2-yl)carbamates (2a-g) and Pyridine -2,6bis-ethyl-N-(1,3,4-thiadiazole) carbamate 1(h): Many routes in the literatures described the synthesis of carbamates (Metcalf et al., 1962;Armstrong et al., 1969), but the most suitable one which was adopted in this work is the reaction of amines with chloroformic ester (Iradj et al., 1971).The reactivity of chloroformic ester was comparable to that of acid chlorides and not ester due to the strong electron withdrawing inductive effect of adjacent chloride which increase the electrophilicity of carbonyl carbon (Izura et al., 1976;Tóth and Almásy, 2005).
Structures of these products were confirmed by their I.R. spectra which were identical to those published for similar compounds (Saied, 1983), and they were 3100-3300 Cm -1,medium for NH stretching, 1720-1730 Cm -1 strong for C=O stretching and 1565-1595, medium, for C = N stretching, this decrease in the frequency (in comparison with that of compounds 1a-h) was due to the decrease of the force constant result from the resonance (produced by the conjugation effects of carbamates groups) (Yukhnovskii, 1967) Scheme (3).
In method (a) Pyridine was used as a base to trap the acid produced at room temperature (Bender, 1960) which gave higher yields (62%-93%) while in method (b) in which the base was sodium carbonate with three-hour refluxed gave yields (30%-80%), Table (2).

CONCLUSION
Microwave irradiation in comparison with conventional methods resolved the important problems in cyclization of thiadiazoles 1(a-h) (the use of the pollutant dehydrating agent phosphorous oxychloride in addition to decrease the work time, increase the products yields, with simplicity in workup).The excellent crystal formation was due to magnesium sulfate.Finally, the new carbamates 2(a-h) were prepared with higher yields, short reaction time using pyridine as a base to trap the acid produced.