Synthesis ,Characterization and biological activity study of new Schiff's bases containing 3,4-dimethyl maleimide moiety

A series of new Schiff's bases containing 3,4-dimethyl maleimide moiety have been synthesized via multisteps synthesis including reaction of 3,4-dimethyl maleic anhydride with aniline producing N-phenyl-3,4-dimethyl maleimide which react with chlorosulfonicacid producing 4-(N3,4dimethyl maleimidyl )phenyl sulfonyl chloride which on amination with hydrazine hydrate yielded in turn 4( N-3 ,4 -dimethyl maleimidyl) phenyl sulfonyl hydrazine and this when condensed with various aromatic aldehydes and ketones afforded the desirable Schiff bases. Structures of the prepared compounds were confirmed by spectroscopic methods including FTIR, 1HNMR,C13NMR spectroscopy and C.H.N analysis.The synthesized Schiff's bases were screened for their antibacterial activity against three microorganisms:Staphylococcus aureus, Escherichia Coli, and Psedomonas aeruginosa. They were found to exhibit high antibacterial activity.

A diversity of biological activities and pharmaceutical uses have been attributed to them such as antinociceptive , antionvulsant and antitumor (8,9) .Moreover a number of researches have reported the using of substituted 3,4dimethyl maleimides in chemotherapy of tumors, ermatomycosis and candidiasis (10).On the other hand biocidal activities of Schiff's bases have also been well established (11) thus a variety of Schiff's bases are reported to show a diversity of interesting biological activities including antibacterial, antifungal,antimouse hepatitis virus (MHV), anticancer and herbicidal activities (12,13).
Biological activities of these compounds in general have been attributed to the toxophoric ( C=N ) linkage in their structures (14) .Keeping these above facts in view we considered it of interest to synthesize a series of new Schiff's bases containing 3,4dimethyl maleimide moiety in their structures.
The new compounds were expected to possess biological activity since their molecules were built from two biologically active components.

Experimental
All chemicals were from BDH,Aldrich and were used without further purification .

1.Preparation of N-phenyl -3,4dimethyl maleimide[1]
Literature procedures (15)were used in preparation of the titled compound with minor modifications.To a solution of (0.01 mole) of 3,4-dimethyl maleic anhydride in (25mL) of ether ,(0.01 mole)of aniline was added drop wise with stirring and cooling.After standing overnight at room temperature the solvent was evaporated to dryness and the residue was dissolved in (10 mL) of acetone followed by filtration .The imide was precipitated with cyclohexane then purified by recrystallization from cyclohexane Yield 77 % m.p.=90-91 0C.

Preparation of 4-(N-3,4-dimethyl maleimidyl) phenyl sulfonyl chloride [2]
The titled compound was prepared according to literatures (16) with some modifications.suitable dry round bottomed flask fitted with dropping funnel (0.01 mole)of In a N-phenyl -3,4-dimethyl maleimide was placed and the dropping funnel was charged with (4 mL) of chlorosulfonicacid.Chlorosulfonicacid was added drop wise during two hours with continuous stirring and keeping temperature at zero 0C .When addition was completed the mixture was stirred at room temperature for (10 hrs) then was poured on crushed ice carefully with stirring.The resulted precipitate was filtered , washed with cold water and dried then purified by recrystallization from methanol Yield 81 % m.p.=165-166 0C .
The test compound solution(0.1mL)was added in the cups and the Petri dishes were subsequently incubated at 37 0C for 48 hrs.Zones of inhibition produced by each compound was measured in mm and the results are listed in Table (6).

Results and Discussion
Since both N-substituted 3,4-dimethyl maleimides and Schiff's bases posses biological activity and have wide spectrum of biological applications, the target of the present work has been directed toward building of new molecules containing the two active moieties dimethyl maleimide and Schiff's base respectively with expected biological activity.
Performing this target was made by multistep synthesis described in scheme (1).
Additionally 13 CNMR spectra of schiff's bases [7,8,9] showed other signals at (156-161.9)ppm which was characteristic signal for imine carbon ( ) and finally compound [9] showed clear signal at (55.6) ppm belong to (OCH 3 ) group which was attached to aromatic ring in this compound .All details of 13 CNMR spectral data of the prepared compounds are listed in Table (4).Moreover Table (5) lists C.H.N analysis for some of the prepared compounds.The prepared Schiff's bases [4][5][6][7][8][9][10][11][12][13][14][15] were expected to possess biological activity since they were built from two biologically active components thus antibacterial activity of the prepared Schiff's bases were examined against two types strains gram positive and gram negative bacteria including staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa.The test results presented in Table (6) showed that most of the new Schiff's bases including (6,7,8,10,12,13,14,15) showed very high activity against staphylococcus aureus while compounds (4,5,9,11) showed high activity against this bacteria .The results showed also that the new compounds are highly active against pseudomonas aeruginosa except compounds (7,11)which are moderately active.
Finally the results indicated high activity of the prepared Schiff's bases against Escherichia Coli except compound (10) which showed moderate activity and compound (7) which was inactive.
As a final conclusion it is interesting to mention that incorporation of 3,4-dimethyl maleimide moiety in Schiff's bases molecules exhibit high biological (antibacterial ) activity and this is fitted with our expections.