ORIGINAL ARTICLE
Org. Commun. 7:2 (2014) 60-67
Microwave induced synthesis of bis-Schiff bases from propane-1, 3-diamine as promising antimicrobial analogs Avinash Shinde1, Sainath Zangade2, Shivaji Chavan2 and Yeshwant Vibhute2* 1 2
Department of Chemistry, N.E.S. Science College, Nanded (MS) India-431605
Organic research center, Department of Chemistry Yeshwant Mahavidyalaya, Nanded (MS) India-431602 (Received August 1, 2013; Revised May 28, 2014; Accepted June 9, 2014)
Abstract: Propane-1,3-diamine 1 on condensation with different halogeno substituted benzaldehydes 2a-p under microwave irradiation affords novel series of bis-schiff bases 3a-p. Structures of the newly synthesized bisSchiff bases established on the basis of spectroscopic data. Further, all compounds screened for antimicrobial activity against Staphylococus aureus, Escherchia coli, Aspergillus niger and Aspergillus flavus. Most of the titles compounds show potent activity. Keywords: 1,3-Diamine; bis-schiff bases; microwave irradiation; microbial activity. © 2014 ACG Publications. All rights reserved.
1. Introduction Schiff bases have been playing vital roles in pharmaceuticals,rubber additives,1 as amino protective groups in the synthetic organic chemistry and several biologically active organic compounds.2-4 They are also useful in analytical5,medicinal6,7 and polymer chemistry.8,9 Besides their utility in phosphorus chemistry, Schiff’s bases have been used for the preparation of αaminophosphonate esters and H-phosphonate esters with repeatable Pudovik reaction10-13 which possess bioactivity such as inhibitor of cancers and viruses and as antibiotics. Particular attention has recently been paid to the synthesis and study of imino, diimino Schiff’s bases and their complexes. This is due to various reasons, such as the biological function of bacteriorhodopsin14. Schiff’s base complexes of small organic molecules with metal cations have found broad applications in the field of interactions with biogenic macromolecules such as DNA, RNA and peptides.15, 16 The microwave induced enhancement of organic reactions is currently a focus of attention for chemists due to the decreased reaction time, improved yields and easier work up as compared to conventional methods.17, 18 In microwave synthesis, to avoid accidents low boiling, toxic and poisonous solvents are often avoided. The use of microwave for the synthesis of organic compounds has proved to be efficient, safe and environmentally benign techniques with shorter reaction time.19 In view of above findings, we have identified the new bis-Schiff bases that may be of value in development of new, potent, selective and less toxic antimicrobial agents. In the present paper, we have successfully to explore the possibility of a greater route with the help of microwave assisted technique for the synthesis of bis-Schiff bases as possible antimicrobial agents. Therefore, this paper describes, for the first time, microwave synthesis, characterization and in vitro antimicrobial activity *
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[email protected]; Tel: +919960128307, Fax: +912462253726 The article was published by Academy of Chemistry of Globe Publications www.acgpubs.org/OC/index.htm © Published 06/19/2014 EISSN:1307-6175
Shinde et al., Org. Commun. (2014) 7:2 60-67
of the bis-schiff bases 3a-p. A comparison of the results obtained from the two synthetic approaches indicate that the effect of microwave irradiation is not purely thermal, besides giving decreased reaction times and improved yields (Table-1).
2. Results and discussion 2.1 Chemistry In view of the application of bis-Schiff bases and in continuation of our earlier investigations, reported on green synthetic strategy towards synthesis of biologically active compounds including Schiff bases.20-25 Therefore in present paper, we synthesized a new class of bis-Schiff bases by the reaction between propane-1,3-diamine (1) with halogeno substituted benzaldehydes (2a-p) by conventional as well as microwave irradiation technique. The use of non-conventional energy over conventional energy for the enhancement of organic reactions that is Microwave Organic Reactions Enhancement provides greater reaction conditions coupled with clean products, increased yield and better time economy.26-29 Thus MW technique has advantage including easy work-up procedure, short reaction time, and does not need effort for isolation of products giving high percentage yield. The structures of products (3a-p) are well confirmed on the basis of spectral data.
Figure 1. Microwave induced synthesis of bis-Schiff bases IR spectra of corresponding condensed product display the characteristic absorption band within 16131636 cm-1 due to C=N stretch. Absence of carbonyl absorption C=O stretch indicate the formation bisSchiff. In the 1H NMR spectra the azomethine (-CH=N) protons appear within δ 8.00 to 9.00 ppm, further the –OH proton resonates between δ13-15 ppm. The aromatic protons are observed at the expected chemical shift and integral values. In the 13C NMR spectra, the imine carbon appears within δ 160.00 to 165.00 ppm. Progress of the reaction can be easily monitored by Thin Layer Chromatography (TLC).
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Microwave induced synthesis of bis-Schiff bases
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Table 1. Physical data for bis-Schiff bases (3a-3p). Entry
R
R1
R2
R3
Yield %
M. P.0C A
B
3a
OH
H
H
H
62
70
80
3b
OH
Br
H
Br
95
72
82
3c
OH
H
H
Cl
100
75
85
3d
OH
H
I
I
160
75
88
3e
OH
H
OH
H
102
60
80
3f
H
OEt
OH
H
70
65
85
3g
H
OEt
OH
Br
130
72
83
3h
H
OEt
OH
I
190
70
80
3i
H
OMe
OH
H
55
72
85
3j
H
OMe
OH
Br
85
70
82
3k
H
OMe
OH
Cl
90
75
88
3l
H
OMe
OH
I
80
70
84
3m
H
H
OMe
OMe
110
75
88
3n
H
OMe
OMe
OMe
123
70
82
3o
H
H
Cl
H
115
65
80
H
120
60
75
3p H H F A: Yield obtained by conventional technique B: Yield obtained by microwave technique
2.2 Antimicrobial activity: The investigation of antibacterial and antifungal screening data revealed that all tested compounds (3a-p) showed good to moderate inhibition at 12.5-200µg/mL in DMSO. The compounds 3c, 3d, 3h, 3k, and 3n showed comparatively good activity against all the bacterial strains. The good activity is attributed to the presence of pharmacologically active –Cl (3c, 3k), I (3d, 3h), -OH (3c, 3d, 3h, 3k), –OEt (3h), and –OMe (3k,3n) groups attached to phenyl group at 2,3 and 4th position in bisSchiff bases. When the substitution of these groups is replaced by hydrogen or another group, a sharp decrease in activity against most of strains was observed. Compounds 3a, 3g, 3l, 3m, 3o exhibited moderate activity compared to that of standard ofloxacin against all the bacterial strain. Further the result showed that Gram-negative exhibited better activity than Gram-positive organism. Compounds 3c, 3d, 3h, 3i, 3o showed comparatively good activity against all the fungal strains, while compound 3f, 3p showed moderate activity against the fungal strains. The structures of these compounds contain biologically active, chloro, iodo, bromo substituted vanilines.
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Shinde et al., Org. Commun. (2014) 7:2 60-67
Table 2. Antibacterial and Antifungal activity of title compounds 3a-3p Entry 3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 3l 3m 3n 3o 3p Ofloxacin Ketoconazole
Zone of inhibition in mm and MIC (minimum inhibitory concentration) in µg/mL S. aureus E.coli A.niger A.flavus 13(100) 17(50) 7(
