Irradiation Assisted Synthesis and Antifungal Activities of Some Mannich Bases *

To eliminate the use of solvent during the course of reaction and to decrease the reaction time in addition to enhanced the yield in synthesis of some Mannich bases 5((5-(Aryloxymethyl)-1,3,4-thiadiazol-2-ylamino)(phenyl)methyl)pyrimidine-2,4,6 (1H,3H,5H)-trione (2a-h),the reaction was carried out under microwave irradiation of equimolecular mixture of 2-amino-5-aryloxymethyl – 1,3,4 –thiadiazoles (1a-h), benzaldehyde and barbituric acid, using magnesium sulfate as absorption support. In conventional method the attempts to react amine(1a)with aldehyde to form Schiff base and the reaction of this base with barbituric acid did not succeed. The structures of these compounds were confirmed by IR Spectrophotometer. All these bases were screened for their antifungal activity against Aspergillus flavus and found to possess weak activity.


INTRODUCTION
At the beginning of this century, List and Barbas showed that the direct asymmetric Mannich reactions of a broad range of ketones and aldehydes were catalyzed by proline, β-Amino ketones and aldehydes can be synthesized stereoselectively in good yields (Barbas et al., 2003;Bahmanyar and Houk, 2003).
In the same way Kidwai et al described the use of montmorillonite clay under microwaves to synthesis novel Mannich bases of thiobarbiturates and barbiturates (Kidwai et al., 2005).
As part of continuous program directed toward the studies with polyfunctionally substituted heterocyclic's (Shandala et al., 1998(Shandala et al., , 2001(Shandala et al., and 2002;;Ayoub et al., 2001;Basher,2005;Al-Gwady, 2007;Saied, 2007), it was became of interest to investigate preparative routs to synthesis of these Mannich bases which contain more than one center of anticipated antifungal activity such as aryloxy heterocyclic ether linkage (Saied, 1983), pyrimidine moiety (Kidwai et al., 2005) and 1, 3, 4-Thiadiazole ring.Several compounds containing one or both of the first two radicals were proved to show promising growth inhibitory action on different fungus especially Aspergillus flavus (Kidwai et al., 2005).The insertion of 1,3,4-thiadiazole ring was based on the reported fungicidal activity of some compounds containing this ring (Saied, 1983).

EXPERIMENTAL
All melting points were determined on a Gallen Kamp and Electro thermal 1A9300 Digital-Series (1998) apparatus and were uncorrected.The IR-spectra (νmax cm -1 ) were recorded on Perkin-Elmer 590B Spectrophotometer.UV-On Shimadzu UV-160 spectrophotometer using EtOH as solvent.
Evaporation of the solvent under reduced pressure yielded the corresponding title compounds 2a-h, which were recrystallized from methanol.%Yields, melting points, in addition to IR were listed in Table (1).

Attempted to synthesis of (2a) by conventional method: (Ralhan et al., 1960)
An equimolar amount of (1a) and benzaldehyde (0.01 mole) were put in a roundbottomed flask.To this, glacial acetic acid in ethanol was added and the reaction mixture was refluxed for 10-12hours with stirrer equipped with condenser.No reaction occurred as checked with TLC, and the precipitate has the same melting point of starting material (1a).

REULTS AND DISCUSSON
Scheme (1) summarizes the synthetic route followed for the preparation of the designed compounds.In this rout benzaldehyde and 2-amino-5-aryloxymethyl-1,3,4- thiadiazoles (1a-h) were reacted with barbituric acid under MW irradiation to give Mannich products (2a-h).In this work, the organic compounds adsorbed on the surface of inorganic magnesium sulfate to support the absorption of microwaves irradiations.The bulk temperature was relatively low in such solvent free reactions although highly localized temperatures may be reached during microwave irradiation.
In conventional method the attempts to react amine (1a) with aldehyde to form Schiff base and the reaction of this base with barbituric acid did not succeed as was referred in literatures (Belinelo et al., 2002;kidawi et al., 2005).
All these bases were screened for their antifungal activity against Aspergillus flavus and found to possess bad activity.(Table 2).

CONCLUSION
The advantages of this work were the safe and simplicity with a good product yield, short reaction time and exclude the volatile and toxic solvents.