Microwave-Assisted Synthesis and Antibacterial Activity of Some New Flavones and 1, 5-Benzothiazepines
VA Navale, SS Mokle, Archana Y Vibhute, KG Karamunge, SV Khansole, SB Junne and YB Vibhute*
P.G. Department of Chemistry, Yeshwant Mahavidyalaya, Nanded 431602 (M.S.) INDIA
*Corresponding Author E-mail: drybv@rediffmail.com
ABSTRACT
The synthesis of heterocyclic compounds containing flavones (4a-i) and 1,5-benzothiazepines(5a-i) from chalcone derivatives containing 3,4-methylenedioxy phenyl ring using microwave irradiation in 80-97% yield within 2 – 4 min. The work-up is simple, shorter reaction time, increase in reaction rate with better yields. The structures of synthetic compounds have been characterized using IR and 1H NMR spectral data together with halogen analysis. All synthesized compounds have been screened for their antibacterial activity.
KEYWORDS: Chalcones, flavones, 1,5-benzothiazepines, microwave irradiation, antibacterial activity.
INTRODUCTION:
Flavonoid compounds are a group of natural products found in fruits, vegetables, nuts, seeds and flowers as well as in teas and are important constituent of human diet. They have been demonstrated to posses antioxdidant1, antihypertensive2, antiallergic3, antinocicepative4, trypsin inhibitors5, antifeedant6, antibacterial and antifungal7, anti-infiammatory8 and antiproliferative9 activities. While 1,5-benzothiazepines also find a unique place in drug discovery programmes as they display a wide range of biological activities such as antibacterial10, anticancer11, analgesic12, antidibetic13, calcium antagonists14, anti-HIV15, endogenous natriuretic factors16 and as potential central nervous system agents.17
In the last few years microwave induced organic reaction enhancement (MORE) chemistry has gained popularity as a non-conventional technique for rapid organic synthesis18 and many researchers have described accelerated organic reactions, and a large number of papers has appeared. Proving the synthetic utility of MORE chemistry in routine organic synthesis19. It has been termed as ‘e-chemistry’ because it is easy, effective, economical and ecofriendly and is believed to be a step toward green chemistry. In view of these observations and in continuation of our work on biologically active heterocycles20, we have been planned to synthesize the new flavones (4a-i) and 1,5-benzothiazepines (5a-i) from chalcones (3a-i) and also studied their antibacterial activity.
The desired chalcones21,22 (3a-i) were synthesized by reacting reacting appropriate halo substituted 2-hydroxyacetophenones (1a-i) with pipernal (2) according to Claisen-Schmidt condensation. In typical case, flavones (4a-i) were prepared by oxidative cyclisation of chalcones (3a-i) using DMSO-I2 reagent under microwave irradiation. While equimolar quantities of chalcones (3a-i) and 2-amino thiophenol in acetic acid under microwave irradiation to obtain 1,5-benzothiazepines (5a-i).
Experimental:
Synthesis of Flavones (4a-i):
Chalcone (0.001 mol) was suspended in DMSO (5 ml) and a crystal of iodine was added to it. The mixture was irradiated in a microwave oven (TLC) for 2-4 min. The progress of reaction was monitored after every 30 sec.of irradiation by TLC with petroleum ether: ethyl acetate (4:1 v/v mixture) as eluent. After each irradiation, the reaction mixture was cooled to room temperature and mixed well. After completion of the reaction (TLC), the solid mass was filtered off, washed with 20% sodium thiosulfate and recrystallised from aqueous ethyl alcohol to give compounds (4a-i).
Table 1: Physical and Analytical data of Flavones and 1,5-Benzothiazepines
|
Comp. Code |
Mol. formula |
Mol. Wight |
Reaction Period (min.) |
M.P. (0OC) |
Yield (%) |
Halogen Analysis X (Cl,Br,I) % Found (Calcd.) |
|
4a |
C16H8O4Cl I |
426.5 |
130 |
170 |
81 |
38.19 (38.10) |
|
4b |
C16H8O4 BrI |
471 |
145 |
164 |
87 |
44.01 (43.94) |
|
4c |
C17H11O4I |
406 |
155 |
166 |
93 |
31.19 (31.28) |
|
4d |
C17H11O4Br |
359 |
170 |
182 |
82 |
22.34 (22.28) |
|
4e |
C16H8O4 I2 |
518 |
165 |
175 |
89 |
48.97 (49.03) |
|
4f |
C16H8O5 Br2 |
440 |
140 |
168 |
91 |
36.47 (36.36) |
|
4g |
C16H8O4 ClBr |
379.5 |
125 |
186 |
84 |
30.49 (30.43) |
|
4h |
C17H10O4 BrCl |
393.5 |
185 |
179 |
96 |
29.28 (29.35) |
|
4i |
C16H8O5 Cl2 |
351 |
150 |
159 |
85 |
20.30 (20.22) |
|
5a |
C22H15O3Cl INS |
535.5 |
175 |
176 |
82 |
30.42 (30.34) |
|
5b |
C22H15O3BrINS |
580 |
140 |
187 |
90 |
35.57 (35.68) |
|
5c |
C23H18O3INS |
515 |
160 |
176 |
83 |
24.74 (24.66) |
|
5d |
C23H18O3BrNS |
468 |
125 |
173 |
97 |
17.19 (17.09) |
|
5e |
C22H15O3I2NS |
627 |
145 |
169 |
88 |
40.57 (40.51) |
|
5f |
C22H15O4Br2NS |
549 |
175 |
199 |
81 |
29.02 (29.14) |
|
5g |
C22H15O3ClBrNS |
488.5 |
150 |
177 |
85 |
22.34 (22.28) |
|
5h |
C23H17O3ClBrNS |
502.5 |
180 |
210 |
94 |
23.07 (22.98) |
|
5i |
C22H15O4Cl2NS |
381 |
145 |
189 |
85 |
18.71 (18.63) |
Table 2: Antibacterial activity data of synthesized compounds
|
Compound code |
Zone of inhibition (mm) |
|||
|
B. subtilis |
E. coli |
X. citri |
E. carotovara |
|
|
4a |
17 |
15 |
20 |
19 |
|
4b |
19 |
20 |
21 |
20 |
|
4c |
12 |
15 |
12 |
10 |
|
4d |
11 |
09 |
14 |
13 |
|
4e |
21 |
20 |
19 |
18 |
|
4f |
20 |
18 |
23 |
21 |
|
4g |
18 |
16 |
16 |
18 |
|
4h |
16 |
18 |
17 |
15 |
|
4i |
24 |
23 |
25 |
24 |
|
5a |
18 |
16 |
19 |
18 |
|
5b |
19 |
18 |
20 |
19 |
|
5c |
13 |
11 |
14 |
15 |
|
5d |
11 |
10 |
15 |
13 |
|
5e |
22 |
18 |
19 |
19 |
|
5f |
23 |
21 |
20 |
22 |
|
5g |
21 |
17 |
22 |
21 |
|
5h |
19 |
18 |
20 |
19 |
|
5i |
26 |
24 |
25 |
25 |
|
Tetracycline 100mg/ml |
24 |
20 |
22 |
22 |
3’,4’-Methylenedioxy-6-methyl-8-iodoflavone (4c):
IR (KBr) cm-1: 1645(C=O), 1587, 1560 (ring C=C).
1HNMR (300 MHz, DMSO): δ7.18-8.20(m, 5H, Ar-H), 6.90 (s, 1H, COCH), 6.28(s, 2H, OCH2O) 2.53 (s, 3H, CH3).
3’,4’-Methylenedioxy-6,8-dibromo-7-hydroxyflavone (4f):
IR (KBr) cm-1: 3400(-OH), 1647(C=O), 1590, 1567 (ring C=C).
1HNMR (300 MHz, DMSO): δ10.65 (s, 1H, Ar-OH), δ7.10-8.05(m, 4H, Ar-H), 6.96 (s, 1H, COCH), 6.35(s, 2H, OCH2O).
Synthesis of 1,5-Benzothiazepines (5a-i):-
Chalcone (0.001 mol) and 2-amino thiophenol (0.001 mol) was dissolved in acetic acid (10ml). The mixture was irradiated in a microwave oven (TLC) for 2-4 min. The progress of reaction was monitored after every 30 sec. of irradiation by TLC petroleum ether/ethyl acetate (4:1 v/v mixture) as eluent. After each irradiation, the reaction mixture was cooled to room temperature and mixed well. After completion of the reaction (TLC), the solid mass was washed with water, dried and recrystallised from acetic acid to obtain pure (5a-i).
Synthesis of 2-(2-Benzo[1,3]dioxol-5-yl)-2,3-dihydro-4-(2’-hydroxy-3’-iodo-5’-methylphenyl)-1,5-benzothiazepine(5c):-
IR (KBr) cm-1: 3385(OH), 2950(saturated C-H), 1607(C=N), 1580, 1555 (ring C=C), 975, 760, 744.
1HNMR (300 MHz, DMSO): δ12.84 (s, 1H, 2-OH), 7.05-8.11(m, 9H, Ar-H), 6.25(s, 2H, OCH2O), 5.41(dd, 1H, HX), 3.45(dd, 1H, HB), 3.12(dd, 1H, HA), 2.61 (s, 3H, CH3).
Synthesis of 2-(2-Benzo[1,3]dioxol-5-yl)-2,3-dihydro-4-(2’4’-dihydroxy-3’,5’-dichlorophenyl)-1,5-benzothiazepine(5i):-
IR (KBr) cm-1: 3405(OH), 2943(saturated C-H), 1605(C=N), 1581, 1555 (ring C=C), 975, 765, 744.
1HNMR (300 MHz, DMSO): δ13.75(s, 1H, 2-OH), 10.84 (s, 1H, 4-OH), 7.0-8.15(m, 8H, Ar-H), 6.27(s, 2H, OCH2O), 5.36(dd, 1H, HX), 3.40(dd, 1H, HB), 3.15(dd, 1H, HA).
In vitro-antibacterial screening:-
The newly synthesized compounds were subjected to antibacterial screening by using cup plate diffusion method23 at 100mg/ml concentration. The antibacterial activity was tested against Escherichia coli, Bacillus subtilis, Xanthomanas citri and Ervinia carotovara using Tetracycline as standard antibiotic. The zone of inhibition was measured using mm scale.
CONCLUSION:
In conclusion, we have synthesized some new flavones and 1,5-benzothiazepines from chalcones under microwave irradiation. Shorter reaction time, simple reaction condition, easy work-up and higher yield render this method superior. From the antibacterial screening it was observed that all compounds exhibited antibacterial activity against all organisms employed. Compound number 4e, 4f, 4i, 5e, 5f, 5g and 5i showed greater or nearly same antibacterial activity than standard drug Tetracycline, where as other compounds showed moderate to good activity.
ACKNOWLEDGEMENT:
Authors are also grateful to UGC New Delhi for sanctioning Major Research Grant and the Director, IICT, Hyderabad for spectral analysis.The authors are also express their sincere thanks to Principal, Yeshwant Mahavidyalaya, Nanded (M.S.) and Head, Department of Biotechnology, Yeshwant Mahavidyalaya, Nanded (M.S.)India for providing the necessary facilities during this work.
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Received on 22.07.2009 Modified on 17.09.2009
Accepted on 10.10.2009 © AJRC All right reserved
Asian J. Research Chem. 2(4):Oct.-Dec. 2009 page 472-475