international journal of chemical and pharmaceutical ... gujurat final.pdf · int. j. chem. pharm....

Int. J. Chem. Pharm. Rev. Res. Vol (1), Issue (2), 2015, Page. 33-37 ISSN No: 2395-3306 Research Article

International Journal of Chemical and Pharmaceutical Review and Research

www.ijcprr.com/browse-journal

Preparation, Characterization and Antimicrobial Studies of Novel Heterocyclic Compounds Purvesh J. Shah* Chemistry Department, K.K.Shah Jarodawala Maninagar Science College, Maninagar, Ahmedabad-380008, Gujarat (India).

A R T I C L E I N F O Article history: Received 30 May 2015 Accepted 22 June 2015 Available online 28 June 2015 Keywords: Imidazole, Benzothiazole derivatives, Antibacterial, Antifungal activities.

A B S T R A C T The cyclocondensation reaction between 2-benzamidoacetic acid I and o-methyl benzaldehyde afforded (Z)-4-benzylidene-2-o-tolyl oxazol-5(4H)-one 2. Then reaction of II with various benzothiazole derivatives III(a-f) was formed a series of novel benzothiazole combined imidazole compounds i.e.4-benzylidene-1-(substitued-2-benzothiazolyl)-2-(4-methoxyphenyl)-1H-imidazol -5(4H)-one IV(a-f). The novel synthesized compounds were characterized by elemental and spectral studies. All the novel synthesized compounds were screened for their antibacterial activities and antifungal activities.

© IJCPRR All rights reserved.

1. Introduction

Now-a-days a number of research work has been carried out on synthesizing of heterocyclic compounds because of majority of the drugs contain heterocyclic moiety, they exhibit various biological activities and also useful according to industrial point of view. Sulphur and nitrogen containing heterocyclic compounds represent an important class of drugs in the therapeutic chemistry1,2.

The heterocyclic compounds which contain two nitrogen in five member ring system, like Imidazole is one of the most researchable heterocyclic compounds due to Imidazole derivatives including saturated imidazoles exhibit various biological activities like, antibacterial, antitubercular, antioxidant, antifungal, anti HIV, anti inflammatory, analgesic, anticancer and anti convulsant activities 3-10.

_____________________________________

* Corresponding author. E-mail address: [email protected] Present address: Chemistry Department, K.K.Shah, Jarodawala, Maninagar Science College, Maninagar, Ahmedabad-380008, Gujarat (India).

Figure 1. Structure of (E)-1-(subsituted benzo[d]thiazol-2-yl)-4-benzylidene-2-(1-methylphenyl)-1H-imidazol-5(4H)-one IV (a-f). The another most important heterocyclic compound like, Benzothiazole shows various biological activities such as antimicrobial11,12 anticancer13, anthelmintic14 and anti-diabetic15 activities. Hence, it continue of our previous work, the current communication contains the study on novel (E)-1-(subsitutedbenzo[d]thiazol-2-yl)-4-benzylidene-2-(1-methylphenyl)-1H-imidazol-5(4H)-one IV(a-f). (Figure-1).

33


2. Materials and methods

All the chemicals used were of Analytical grade. The IR spectra were recorded in KBr pellets on a Nicolet 400D spectrometer and 1H NMR and 13C NMR spectra were recorded in DMSO with TMS as internal standard on a Bruker spectrometer at 400 MHz and 100 MHz, respectively. Melting points were determined in open capillary tubes and were uncorrected.

2.1 Synthesis of (Z)-4-benzylidene-2-o-tolyloxazol-5(4H)-one II

The mixture of 2-benzamidoacetic acid I (0.1mole), o-methyl benzaldehyde (0.1mole), anhydrous sodium acetate (0.1mole) and acetic anhydride (0.2mole) warmed on water bath with irregular stirring until solution is complete. The resulting solution was boiled for 2.5 hrs, cooled to 0-5oC and stired the yellowish white solid product with water. The solid separated was collected by filtration, washed with petroleum ether, dried and recrystallized from ethyl acetate. The yield of the product was 68 % and the product melts at 148-149oC. C17H13NO2(263)Calcd.:%C,77.55;%H,4.98;% N,5.32,Found:%C,77.54;%H,4.96;%N,5.30.

IR(KBr,cm-1):3080-3060 (AromaticC-Hstretch), 2852 (CH3),760 (Aromatic C-H bending), 1620-1580 (Aromatic C-C stretch),1790 (C=O lacton), 1650 (C=N), 1262 (C-N). 1HNMR: 7.78–7.22 (9H, m,Ar-H), 7.98 (1H,s C=CH), 2.45 (3H,s,CH3). 13C NMR: 166.4 (COlacton), 163.3-114.6 (Ar-C), 161.3 (C=N), 131.9,112.7 (C=C), 20.4(CH3).

2.2 Synthesis of 2-amino-4-substitued benzothiazoles III(a-f)

The solution of various substituted aniline (0.2 mole) and potassium thiocyanate (0.8 mole) in glacial acetic acid was added drop wise to 20% bromine glacial acetic acid (0.2 mole) with stirring, while the temperature was kept below 32oC. After all the bromine solution had been added. The mixture was stirred for about 10 hrs, then filtered and then washed with water. The combined filtrate and washings were neutralized with ammonium hydroxide. The precipitate was collected and dried. The yields, melting points and other characterization data of these compounds are given in Table-1.

2.3 Synthesis of (E)-1-(subsituted benzo[d]thiazol-2-yl)-4-benzylidene-2-(1-methylphenyl)-1H-imidazol-5(4H)-one IV(a-f)

A mixture (Z)-4-benzylidene-2-o-tolyloxazol-5(4H)-one II (0.01mole) and 2-amino-4-substituted benzothiazoles III(a-f) (0.01mole) was refluxed in presence of pyridine for 6-8 hours. Excess of pyridine was distilled off and resulting mass was poured on to

crushed ice and neutralized with acid, filtered and crystallized from ethanol. The yields, melting points and other characterization data of these compounds are given in Table-2.

Table 1. Analytical Data and Elemental Analysis of Compounds III(a-f)

2.4 Biological Screening

Antibacterial Activity

The antibacterial activities of all the compounds were studied against gram-positive bacteria (Staphylococcus Aureus and Bacillus Subtilis) and gram-negative bacteria (E.coli and Klebsiella Promioe) at a concentration of 50μg/mL by agar cup plate method. A methanol system was used as control in this method. The area of inhibition of zone measured in mm. Compounds III(c), III(e), IV(c) and IV(e) were found more toxic for microbes. Other compounds found to be less or moderate active than these compounds (Table-3).

Compd. M.P.*

0C

(Yield)

Elemental Analysis

%C %H %N %S

Calcd.

(Found)

Calcd.

(Found)

Calcd.

(Found)

Calcd.

(Found)

IIIa

159

-161

(72)

55.97

(55.96)

4.03

(4.02)

18.65

(18.64)

21.35

(21.33)

IIIb

162

-164

(67)

58.51

(58.49)

4.91

(4.88)

17.06

(17.05)

19.52

(19.51)

IIIc

153

-156

(64)

53.31

(53.28)

4.47

(4.45)

15.54

(15.52)

17.79

(17.78)

IIId

156

-158

(68)

43.07

(43.06)

2.58

(2.56)

21.53

(21.52)

16.43

(16.42)

IIIe

153

-155

(70)

45.53

(45.51)

2.73

(2.71)

15.17

(15.16)

17.37

(17.36)

IIIf

161

-163

(67)

36.70

(36.69)

2.20

(2.18)

12.23

(12.22)

14.00

(13.98)

34


Antifungal Activity

The fungicidal activity of all the compounds was studied at 1000 ppm concentration in vitro. Plant pathogenic organisms used were Aspergillus Niger, Botrydepladia Thiobromine and Nigrospora Sp. The antifungal activity of all the compounds III(a-f) and IV(a-f) were measured on each of these plant pathogenic strains on a potato dextrose agar (PDA) medium. Such a PDA medium contained potato 200g, dextrose 20g, agar 20g and water 1ml. Five days old cultures were employed. The compounds to be tested were suspended (1000ppm) in a PDA medium and autoclaved at 120o C for 15 min. at 15atm. pressure. These media were poured into sterile petri plates and the organisms were inoculated after cooling the Petri plates.

Table 2. Analytical Data and Elemental Analysis of Compounds IV(a-f)

The percentage inhibition for fungi was calculated after five days using the formula given below: % of inhibition = 100(X-Y) / X

Compd. M.P.*

0C

(Yield)

Elemental Analysis

%C %H %N %S

Calcd.

(Found)

Calcd.

Found

Calcd.

Found

Calcd.

Found

IVa

177

-178

(68)

70.05

(70.04)

4.16

(4.14)

10.21

(10.19)

7.79

(7.78)

IVb

164

-166

(66)

70.57

(70.55)

4.50

(4.48)

9.88

(9.86)

7.54

(7.52)

IVc

179

-181

(62)

68.01

(67.99)

4.34

(4.32)

9.52

(9.51)

7.26

(7.24)

IVd

172

-174

(60)

63.15

(63.14)

3.53

(3.52)

12.27

(12.26)

7.02

(7.01)

IVe

169

-171

(69)

64.64

(64.63)

3.62

(3.60)

9.42

(9.41)

7.19

(7.17)

IVf

176

-178

(61)

58.78

(58.76)

3.29

(3.27)

8.57

(8.55)

6.54

(6.53)

Where, X = Area of colony in control plate; Y = Area of colony in test plate

The fungicidal activity displayed by various compounds III(a-f) and IV(a-f) are shown in Tables-3.

Table 3. Antibacterial and Antifungal Activity of Compounds III(a-f) and IV(a-f)

Compd. Gram +Ve

Gram

-Ve Zone of Inhibition at 1000ppm (%)

SA BS E KP AN BT NS

IIIa 52 51 59 61 61 60 59

IIIb 51 57 54 64 56 52 58

IIIc 62 68 71 73 70 68 69

IIId 50 57 69 65 63 62 60

IIIe 55 65 70 78 65 63 62

IIIf 53 59 67 70 59 57 60

IVa 53 55 64 64 63 62 60

IVb 54 58 58 66 60 56 62

IVc 67 74 78 79 74 70 72

IVd 57 68 71 68 66 64 62

IVe 65 70 72 73 68 69 65

IVf 55 67 69 72 62 60 63

Where, SA=Staphylococcus aureus; BS= Bacillus Subtilis; E=E.coli; KP=Klebsiella Promioe; AN= Aspergillus Niger; BT= Botrydepladia Thiobromine and NS= Nigrospora Sp.

3. Results and Discussion

In present communication, the condensation reaction between 2-benzamidoacetic acid I with o-methyl benzaldehyde gives (Z)-4-benzylidene-2-o-tolyloxazol-5(4H)-one II. The structures of II were confirmed by elemental analysis and IR spectra showing an absorption band at 3080-3060(Aromatic C-H stretch), 2852(CH3), 760 (Aromatic C-H bending),1620-1580 (Aromatic C-C stretch),1790(C=O lacton),1650 (C=N), 1262 (C-N); 1H NMR:7.78–7.22(9H,m,Ar-H), 7.98 (1H,s,C=CH),2.45(3H,s,CH3).13CNMR: 166.4 (COlacton), 163.3-114.6 (Ar-12C),161.3 (C=N),131.9, 112.7(C=C), 20.4(CH3).For C17H13NO2(263)Calcd.: %C,77.55;% H,4.98; %N,5.32, Found:%C,77.54;%H,4.96;%N,5.30. The structures assigned to various substituted benzothiazole III(a-f) were supported by the elemental analysis and IR spectra showing absorption bands at

3475cm-1(NH2),3030-3080 cm-1 (Aromatic C-H stretch) ,1542cm-1 (Aromatic C=C),1560cm-1(C=N), 615cm-1(C-S),1120cm-1(OCH3),1452cm-1(NO2),686 cm-1(Aromatic C-Cl),1076cm-1(Aromatic C-Br); 1HNMR: 7.06 (2H,s,NH2),IIIa:8.20-7.65(4H,m,Ar-H), IIIb: 8.02-7.40 (3H,m,Ar-H),2.46(3H,s, CH3), IIIc: 8.22-7.60(3H,m,Ar-

35


H), IIId:8.80-7.70(3H, m, Ar-H),IIIe:7.60-7.10(3H,m,Ar-H), IIIf: 8.70-8.20 (3H,m,Ar-H); 13C NMR:166.8 (C=N), IIIa:153.6,131.4,125.6,124.8,122,118.8(Ar-C), IIIb: 150.4, 134.3, 131.2, 126.8, 121.5 (Ar-C), 21.2 (CH3), IIIc:151.6, 132.8, 130.2, 126, 121.4, 118.5 (Ar-C), IIId:152.4, 133.2, 129, 124.3, 119.2, 117.4 (Ar-C), IIIe:157.2, 145.8, 132.4, 118.6, 114.8, 105.6 (Ar-C), IIIf:159.6,144.8,131.5, 121.6, 119.5,117.8 (Ar-C). The C, H, N, S analysis data of all compounds are presented in Table-1.

IR spectra of III(a-f) are almost resemble those of the corresponding IV(a-f) only discernable variation observed that the bend at 3475cm-1(NH2) is absent and the new bands at 3080-3060(Aromatic C-H stretch), 2852(CH3),760(Aromatic C-H bending),1620-1580 (Aromatic C-C stretch),1790(C=O lacton), 1650 (C=N), 1262(C-N) are observed in all the spectra of IV(a-f), which might be responsible for formation of imidazole ringsystems.1H NMR: 7.45(1H,s,CH=C),2.46(3H,s,CH3), IVa: 8.15-7.09(13H,s,Ar-H),IVb:7.89-7.35(12H, m, Ar-H), 2.42(3H,s,CH3), IVc: 7.83-7.01(3H,m, Ar-H), 3.78 (OCH3), IVd:8.63-7.06(12H,m,Ar-H),IVe:8.56-7.03 (12H,m,Ar-H), IVf: 8.56-7.05(12H,m,Ar-H); 13C -NMR:139.7, 135.4,130.2, 129.3, 129.3, 128.9, 128.9, 128.9, 128.8, 128.7, 128.5,128.3(Ar-C),130.6, 114.7 (C=C), 170.4 (C=O of imidazole ring),158.1(C=N),160.3 (C=N of benzothiazolering),21.7(CH3), IVa: 139.7,135.5, 125.4,124.8,122.2,118.6(Ar-C), IVb:147.3,131.4, 126.8,126.2,124.7,119.2(ArC),16.5(CH3),IVc:150.3,142.6,132.3,122.1,114.4,105.5(Ar-C),56.1 (OCH3), IVd: 145.2, 142.2, 128.3,125.9,125.5,122.7(Ar-C),IVe:149.4, 132.6,126.1,122.2,121.8,120.3(Ar-C),IVf: 151.7, 128.8, 128.5,126.8,121.2,116.7(Ar-C). The C,H,N,S analysis data of all compounds are presented in Table-2. The examination of elemental analytical data reveals that the elemental contents are consistence with the predicted structure shown in Figure-1. The IR data also direct for assignment of the predicted structure. 4. Conclusion

In present article, we reported novel synthesis and characterization of (E)-1-(subsitutedbenzo[d]thiazol-2-yl)-4-benzylidene -2-(1-methylphenyl)-1H-imidazol-5(4H)-ones by an exceptionally efficient process. All the novel synthesized heterocyclic compounds show moderate to excellent antibacterial and antifungal activities.

References

1. Patel N.B. and Shaikh F.M. New 4-thiazolidinones of nicotinic acid with 2-amino-6-methyl benzothiazole and their biological activity., Sci Pharm.,78:753-765, (2010).

2. Shah P.J.Synthesis and Biological Activity of Novel Imidazole,Current Trends in Bio technology and Chemical Research,2 (1):45-51, (2012).

3. Raghavendra P., Veena G., Kumar G. A., Kumar E. R., Sangeetha N., Sirivennela B.,Smarani S., Kumar H. P., Suthakaran R. Synthesis, Antioxidant and Antimicrobial Study of Novel Imidazolo-Quinoline Derivatives, International Journal of Chemical and Analytical Science, 2(6): 62-69, (2011).

4. Shalini K., Sharma P.K., Kumar. N. Imidazole and its biological activities: A review.Chem Sin, 1: 36-47, (2010).

5. Husain A., Drabu S., Kumar N. Synthesis and biological screening of di- and tri substituted imidazoles. Acta Pol Pharm-Drug Res,66:243-8,(2009).

6. Robert J.G.,Daryl S.W.,Paul J.B., Elena F., Anton D.M., Shilina A.R. Synthesis and biological activity of a series of tetra substituted-imidazoles as P2X 7 anta gonists.Bioorg Med Chem Lett,20: 4951 - 4, (2010).

7. Neves J.K., Botelho S.P., de Melo C.M., Pereira V.R., de Lima M. C., Pitta I.R. Biological and immunological activity of new imidazolidines against adult worms of Schistosoma mansoni. Parasitol Res, 107: 531-8, (2010).

8. Sharma V., Khan M.S.Synthesis of novel tetrahydroimidazole derivatives and studies for their biological properties. Eur J Med Chem,36:651-8,(2001).

9. Khan M.S.,Chawla G.Tetrahydro imidazoles -A promising group of expected NSAIDS-their synthesis and antiinflammatory activity. Indian J Chem, 41B: 653-63, (2002).

10. Khan M.S.,Gupta M.Synthesis and evaluation of antiinflammatory and analgesic activity of some new 1,3-diphenyl -2-Aryltetrahydroimidazoles. Indian J Chem, 42B: 2086-90, (2003).

11. Gupta S.,Ajmera N.,Gautam N., Sharma R., Gauatam D. Novel synthesis and biological activity study of pyrimido [2,1-b] benzothiazoles. Ind. J Chem., 48B: 853-858, (2009).

12. Kumbhare R.M., Ingle V.N.Synthesis of novel benzothiozole and benzisoxazole functionalized unsymmetrical alkanes and study of their antimicrobial activity. Ind J Chem., 48B: 996-1000. (2009).

13. Stanton H.L.K., Gambari R., Chung H.C., Johny C.O.T., Filly C., Albert S.C.C. Synthesis and anti-cancer activity of benzothiazole containing phthalimide on human carcinoma cell lines. Bioorg Med Chem.,16: 3626-3631, (2008).

36


14. Sreenivasa M., jaychand E., Shivakumar B., Jayrajkumar K., Vijaykumar J.Synthesis of bioactive molecule flurobenzothiazole comprising potent heterocylic moieties for anthelmintic activity. Arch Pharm Sci and Res.,1(2):150-157, (2009).

15. Pattan S.,Suresh C., Pujar V.,Reddy V., Rasal V.,Koti B. Synthesis and antidiabetic activity of 2-amino [5”(4-sulphonylbenzy lidine)-2,4-thiazolidinenone]-7-chloro-6-fluro benzothiazole. Ind J Chem., 44B: 2404-2408, (2005).

37

international journal of chemical and pharmaceutical ... gujurat final.pdf · int. j. chem. pharm....

Documents