SYNTHESIS AND MICROBIAL STUDIES OF SOME NOVEL SCHIFF BASE CONTAINING PYRIMIDINE

SYNTHESIS AND MICROBIAL STUDIES OF SOME NOVEL SCHIFF BASE CONTAINING PYRIMIDINE

Kalpesh S. Parikh* and Sandip P. Vyas

Department of Chemistry, Sheth M.N. Science College, Patan-384 265, Gujarat, India

ABSTRACT

6-chloro 2, 4-diamino pyrimidine reacts with various aromatic aldehyde. Finally, the product was characterized by conventional and instrumental methods. Their structures were determined and important therapeutic properties were studied.

Microbial Studies

INTRODUCTION: Azomethines are generally known as Schiff bases to honour Hugo Schiff, who synthesized such compounds. These are the compounds containing characteristic -C=N- group. Several methods have been reported for the preparation of azomethines. Selvam et.al¹ have prepared sulfonamide and its derivatives as anti-HIV agents. More et. al have marked the biological activity of Schiff bases synthesized from aminothiazoles. Ernst Bayer has reported some metallocomplex Schiff bases derived from o-amino phenol. Schiff bases can be synthesized from an aromatic amine and a carbonyl compound by nucleophilic addition forming a hemiaminal, followed by a dehydration to generate an imine. They are well known intermediates for the preparation of azetidinones, thiazolidinones, oxadiazolines and many other derivatives. Azomethines exhibit a wide range of pharmacological activities like antimicrobial, antiparasitic, anti-inflammatory, anticancer etc.  Pyrimidine and their derivatives posseses several interesting biological activity such as antimicrobial ^2-4, antitumor, antifungal activities.  Many pyrimidine derivatives are used for thyroid drugs and leukemia.

MATERIALS AND METHODS: The reagent grade chemicals were obtained from commercial sources and purified by either distillation or recrystallization before use.  Purity of synthesized compounds has been checked by thin layer chromatography.  Melting points were determined by open capillary method and are uncorrected.  IR spectra are recorded on FT-IR Bruker with KBr disc. ¹H NMR spectra are recorded in DMSO-d6 on a Bruker DRX-400 MHz using TMS as internal standard.  The chemical shift are reported as parts per million (ppm) and mass spectra were determined on Jeol-SX-102(FAB) spectrometer.

Synthetic Procedures:

Preperation of 6-chloro 2, 4-diamino pyrimidine: Take 3 neck flask, T.P, Stirrer, Purger, Charge Barbutiric acid, POCl3 and PCl3, now heat the R.M. till 70^oC temperature, now pass Cl2 gas and temperature rise up to 100°C so, three Hydroxyl group replace by three chlorine group, progress of the reaction was monitored by TLC. So, here formation of 2, 4, 6 tri chloro pyrimidine. Now, in autoclave taken Liq. NH3 and cool it 0^oC temperature, now add 2, 4, 6 tri chloro pyrimidine slowly into it, now heat the RM till 70°C temp. and maintain for 1-2 hrs., then raise the temp., till 100°C and maintain for 1-2 hrs.  Progress of the reaction was monitored by TLC. After the completion of the reaction, filter it and W/C washed with water, suck dry well, then purified in Methanol.

Preparation of 6-chloro-N2-[(Z)-phenylmethylidene] pyrimidine-2,4-diamine: To a mixture of 6-chloro pyrimidine-2,4-diamine  (0.1 mol.) and substituted aromatic acetophenone (0.1 mol.) in ethanol, 1 ml. of glacial acetic acid added then the resultant mixture was refluxed for (5-6 hours), progress of the reaction was monitored by TLC. After the completion of the reaction, the obtained product was poured into crushed ice stirred well; solid obtained was recrystallized from suitable solvent. Their Analytical data and synthetic procedure shown in Tabel 1 and Scheme 1.

FIGURE 1: SYNTHETIC ROUTE OF SCHIFF BASE DERIVATIVES

TABLE 1: PHYSICAL CONSTANTS AND ELEMENTAL ANALYSIS OF SCHIFF-BASE

RESULTS AND DISCUSSION:

Therapeutic Study:

Antibacterial activity: Antibacterial activity was carried out by browth dilution method ⁵.  The compounds SP_v-1-10 were screened for their antibacterial activity against Escherichia coli, Staphylocous aureus, Pseudomonas aeruginosa and Staphyloccous pyogenes of concentrations of 1000, 500, 200, 100, 50, 25, 12.5 µg/mL respectively.

Antibacterial activity results showed that, compound SP_V-03 and SP_V-04  were good active

Antifungal activity: Same compounds were tested for antifungal activity against C. albicans A. niger and A. clavatus of a concentrations of 1000, 500, 200, 100 µg/mL respectively.  The results are recorded in the form of primary and secondary screening.  Each synthesized drug was diluted to obtain 1000 µg/mL concentration, as a stock solution.

The data of antifungal activity of this series indicated that, compounds were not showing potential activity against any species. Their Antifungal data are given in Table 2.

TABLE 2:                ANTIBACTERIAL AND ANTIFUNGAL ACTIVITY DATA

CONCLUSION: The Schiff base were synthesized and characterized for their structure elucidation.  Various chemical and Spectral data supported the structure thought of Antibacterial and Antifungal studies of these compounds indicated that  SP_v-03 and SP_v-04 were good active against all bacteria while all compounds were not showing potential antifungal activity against any species.

ACKNOWLEDGMENTS: We are grateful the SAIF, Punjab University for recording the ¹H NMR, Oxygen Health care Research Pvt. Ltd., Ahmedabad for recording Mass Spectra and M.N. Science college, Patan for recording IR Spectra.

REFERENCES

1. Selvam P., Chandramohan M., De Clercq E., Wityrouw M. and annecouque C.: Synthesis and anti –HIV activity of 4-[(1,2-dihydro-2-oxo-3H indol-3-ylidene) amino]-N (4,6-dimethyl-2-pyrimidinyl)-benzene sulfonamide and its derivatives. Eur. J. Pharm. Sci, 2001; 14(4) : 313-316.
2. Parikh K.S. and Vyas S.P.: Synthesis, Characterization and Antimicrobial activity of a New series of s-Triazines derived with Pyrimidines. American J of Pharmtech Res., 2012, 2(1) : 570-576.
3. Parikh K.S. and Vyas S.P.: Synthesis of some new s-Triazine based derivatives as potent antimicrobial agents. Der Chemica Sinica, 2012, 3(2) : 426-429.
4. Parikh K.S. and Vyas S.P: Synthesis and antimicrobial screening of some new s-Triazine based piperazine and piperidine derivatives. Der Chemica Sinica, 2012, 3(2),430-434.
5. National Committee for clinical Laboratory standard, Reference method for broth dilution antifungal susceptibility testing of yeasts approved standard M27A, NCCLS, Wayne, PA, 1997.
   

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   Parikh KS and Vyas SP: Synthesis and Microbial Studies of Some Novel Schiff Base Containing Pyrimidine.Int J Pharm Sci Res, 2012; Vol. 3(9): 3425-3427.

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