Synthesis of 2-methoxy-6-(pyrazin-2-ylimino methyl) phenol and its antibacterial activitity

A. A. jarrahpour ^1,*,M. Motamedifar ²,N. Hadi ², M. Zarei ¹

1.Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran Tel  0098 711 2284822,  Fax: 0098 711 2280926

E-mail: [email protected],  [email protected]

2.Department of Bacteriology & Virology ,  Shiraz Medical School , Shiraz  University Medical Science , Shiraz  71345, Iran

Received: 30 January 2004 / Accepted: 18 February 2004 / Published: 24 February 2004 

Keywords : Schiff base, 2-amino pyrazine, o-vanillin, antibacterial activity, heated food.

Pyrazines are found in such heated foods as bread, different meats, baked potatoes and coffee [1],which are formed from serine and thereonine [2]. Pyrazine compounds have shown antifungal [3], antimyco- bacterial [3-4] activities. Furthermore, pyrazine derivatives have been used as antioxidation compounds [3,5-6]. Schiff bases have been used as ligands in complex formation with some metal ions [7]. They have shown biological activities including antibacterial [8-10], antifungal [9-11], anticancer [12-13] and herbicidal [14] activities. On the other hand, Schiff bases have applied as starting materials in the synthesis of a large bioactive and industrial compounds via ring closure, cycloaddition, replacement reactions, etc [15]. In addition, the methoxy group on the molecule enhances the various biological activities [16]. According to above facts, we synthesized 2-methoxy-6-(pyrazin-2-ylimino methyl) phenol 3 and then it was tested against four microorganisms Staphylococcus aureus (Gram positive), Bacillus subtilis (Gram positive), Kelebsiella pneumonia (Gram negative) and Pseudomonas aeruginosa (Gram negative). Compound 3 was moderately active against Kelebsiella pneumonia at 200 μg and it was inactive against other mentioned bacteria.  

A mixture of 2-amino pyrazine 1 (0.95 g, 10.00 mmol), o-vanillin (2-hydroxy-3-methoxy benzaldehyde) 2 (1.52 g, 10.00 mmol) and anhydrous sodium sulfate (3.00 g) in dry dichloromethane (40.00 mL) was stirred at room temperature for five hours. The suspension was filtered and washed with CH₂Cl₂.The solvent was evaporated under reduced pressure and imine 3 was formed as a red solid which was recrystalized from methanol (1.90 g , 83%).

m.p.132-134 ^oC.

IR (KBr) (cm^-1): 1575.73 (CH=N ), 1610.45 (C=N ring), 3190.5 -3645.20 (OH).

¹H-NMR(CDCl ₃) (250 MHz)(ppm): 3.87 (3H, s, OCH₃), 6.81-7.20 (3H, m, aryl hydrogens), 8.3-8.6 (3H, m, pyrazin ring), 9.3 (1H, s, N=CH), 13.30 (1H, br, OH).

¹³C- NMR (CDCl₃) (62.90 MHz)(ppm): 56.64 (OCH₃), 116.47-142.90 (aryl and pyrazine carbons), 167.30 (N=CH).

MS (m/z, %): 229 (M⁺, 60.3), 150 (HOPhOCH₃CH=N, 22.0), 135 (HOPhOCH₃C, 18.0), 106 (C₄N₂H₃ N=C, 14.0), 79.0 (C₄N₂H₃, 44.4), 43 (C-OCH₃, 100.0), 41 (N=CH-N, 96.0).

Acknowledgment

The authors thank the Shiraz University Research Council for financial support (Grant No. 81-SC-1540-C220 ).

References

1.   Buchbauer, G.; Klein, C.Th.; Wailzer, B.; Wolschann, P. J. Agric. Food Chem. 2000, 48, 4273-4278.

2.   Chi-Kuen Shu J. Agric. Food Chem. 1999, 47, 4332-4335.

3.   Dolezal, M.; Miletin, M.; Kunes, J.; Kralova, K. Molecules 2002, 7, 363-373.  

4.   Gezginci, M. H.; Martin, A. R.; Franzblau, S. G. J. Med. Chem 2001, 44, 1560-1563.    

5.   5.   Jeanjot, P.; Bruyneel, F.; Arrault, A.; Gharbi, S.; Cavalier, J.-F.; Abels, A.; Marchand, C.; Touillaux, R.; Rees, J.-F.; Marchand-Brynaert, J. Synthesis 2003, (4), 513-522. 

6.   6.  Cavalier, J.-F.; Burton, M.; De Tollenaere, C.; Dussart, F.; Marchand, C.; Rees, J.-F.; Marchand- Brynaert, J. Synthesis 2001, (5), 768-772.   

7.   Tai, X.; Yin, X.; Chen, Q. and Tan, M. Molecules 2003, 8, 439-443.     

8.   8.   Kabeer, A . S.; Baseer, M. A.; Mote, N. A. Asian J. Chem. 2001, 13 (2), 496-500. 

9.   9.   More, P. G.; Bhalvankar, R . B.; Pattar, S. C. J. Indian Chem. Soc. 2001, 78 (9), 474-475.   

10. Pandeya, S. N.; Sriram, D.; Nath, G.; De Clercq, E. IL Farmaco 1999, 54, 624-628.  

11. Singh, W. M.; Dash, B. C. Pesticides 1988, 22 (11), 33-37.  

12. Hodnett, E. M. and Dunn, W. J. J. Med. Chem. 1970, 13, 768-770.  

13. Pathak, P.; Jolly, V. S.; Sharma,K. P. Orient. J. Chem. 2000, 16(1), 161-162.              

14. Samadhiya, S.; Halve, A. Orient. J. Chem. 2001, 17 (1), 119-122.      

15. Aydogan, F.; Öcal, N.; Turgut, Z. and Yolacan, C. Bull. Korean Chem. Soc. 2001, 22, 476-480. 

16. Halve, A.; Goyal, A. Orient. J. Chem. 1996, 12(1), 87-88.

Sample Availability : Available from MDPI. 

© 2004 MDPI. All rights reserved