Preparation and Identification of some new Compounds 1,3,4-Oxadiazole derivatives using Grinding Technique

 

Muhammed. Khidir. M¹, Ayad. Sulaiman. H², Nihad. Ismael. T³

¹Ministry of Environment, Department of Protection and Improvement of Environment, Northern Region, Kirkuk, Iraq.

²Department of Chemistry, College of Education, University of Tikrit, Iraq.

³Department of Chemistry, College of Science, University of Kirkuk, Iraq.

 

ABSTRACT:

A new series of 2-((1H-Benzo[d]imidazole-1-yl)methyl)-5-(3-substituted phenyl)-1,3,4-oxadiazole have been synthesized, using grinding technique. The structures of new compounds have been confirmed by spectral and analytical data.

 

 

 

INTRODUCTION:

Benzo[d] imidazole and its derivatives are of great importance in medicinal chemistry because of their wide variety of biological and pharmacological applications [1,2]. A large number of benzimidazole derivatives have been found to exhibit various biological activities such as anti-inflammatory [3,4], antifungal [5,6] ,antibacterial [7,8], and anthelmintic [9] activities, etc. similarly, a number of oxadiazole derivatives were also reported to possess varied biological activities such as anti-inflammatory [10], antibacterial [11,12], fungicidal [13,14], analgesic, muscle relaxant and tranquilising[15] properties. fascinated by the varied biological activity of benzimidazole and oxadiazole derivatives it was contemplated to synthesize a new series of 1,3,4-oxadiazoles carrying benzimidazole moiety.

 

 

 

MATERIALS AND METHODS:

IR spectra were obtained on a Sidco Biotech FT-IR 600 spectrometer (KBr pellets). The UV-Visible spectra were recorded onShimadzu UV-210 Double Beam Spectrophotometer. H¹ and C¹³ NMR spectra were recorded on aBruker advance (400MHz) spectrometer using tetra methyl silane as internal standard in DMSO-d₆. The elemental analysis was carried out by using EA Euro vector 3000 element analyzer. Melting points were determined by open tube capillary method and are uncorrected. progress of the reaction and purity of the products was checked by thin layer chromatography (TLC). The spots were located under iodine vapors.

 

General procedure for the preparation of ethyl benzimidazole acetate(1):

The solution of Benzimidazole (0.06 mole) in acetone (40 ml) was mixed with ethyl chloroacetate (0.07 mole) and potassium carbonate (0.12 mole) and refluxed for (6 hr), completion of the reaction was monitored by (TLC), The reaction mixture was filtered, from the clear filtrate, excess acetone was removed by distillation and then was added to water. The solid product separated was collected by filtration and dried. further purification was done by crystallization from ethyl acetate. M.P. 88-90 °C, Yield 86%, Colour white. as well as identification of the ester (1) by using chemical detectors, the detection test known as (Ferric hydroxamate) give positive result, which denoteʼs the existence of ester[16].

 

General procedure for the preparation of benzimidazole acetic acid hydrazide(2):

The solution of ethyl benzimidazole acetate (1) (0.04 mole) in ethanol (25 ml) was mixed with hydrazine hydrate (99%) (0.04 mole) and refluxed for (4 hr), completion of the reaction was monitored by (TLC), The excess of solvent was removed by distillation and the contents were added to excess of water. The crude product was purified by recrystallization from ethanol . M.P. 180-181 °C, Yield 90%, colour Grey.

 

Procedure for the preparation of oxadiazoles(3-13):

(0.01 mole) of benzimidazole acetic acid hydrazide (2) mixed with (0.01 mole) of different substituted benzaldehyde, then added (0.001 mole) of iodine molecule to the mixture in the porsline mortar and was grind with pestle for (8 minutes). The reaction was followed by thin layer chromatography (TLC), after compellation of reaction was use sodium thisulphate (10%, 10 ml) to remove iodine present. The solid product was filtered and washed with water, and using ethanol for recrystallization to give pure product [17].

Anal.Calcd. for(6) C₁₈H₁₄N₄O:C, 71.51;H,4.67;N,18.53. Found: C, 71. 53;H,4.72;N,18.61 %.

 

Anal. Calcd. for (8) C₁₆H₁₂N₄O₂: C,65.75; H,4.14; N, 19.17. Found:C, 65.84;H, 4.32; N, 19.28 %.

 

Procedure for the preparation of 1,4-bis [(Benzimidazole methyl)-1,3,4-oxadiazole] benzene(14):

(0.01 mole) of Benzimidazole acetic acid hydrazide (2) mixed with (0.005 mole) of terephthalaldehyde then added (0.001 mole) of iodine molecule to the mixture in the porsline mortar and was grind with pestle for (8 minutes). The reaction was followed by thin layer chromatography (TLC), after compellation of reaction was use sodium thisulphate (10%, 10 ml) to remove iodine present. The solid product was filtered and washed with water, and using ethanol for recrystallization to give pure product [17].

 

Anal.Calcd. for C₂₆H₁₈N₈O₂:C,65.82;H,3.82;N, 23.62. Found: C, 65.84;H,3.86;N,23.56 %.

 

Scheme I

 

Table (1) : Physical data for 1,3,4-oxadiazole derivatives

No. Comp	Ar (R)	Molecular formula	Colour	M.P. (°C)	Yield %
3	(H)	C16H12N4O	white	208-210	91
4	(2-Cl)	C16H11ClN4O	White-yellowy	214-215	86
5	(3-OH)	C16H12N4O2	White-yellowy	189-190	61
6	CH=CHPh	C18H14N4O	Leady	253-254	95
7	(4-NO2)	C16H11N5O3	Yellow	195-196	94
8	(4-OH)	C16H12N4O2	Light grey	197-198	75
9	(4-Cl)	C16H11ClN4O	white	220-221	80
10	(4-N(CH3)2)	C18H17N5O	orange	240-242	72
11	(4-OCH3)	C17H14N4O2	White	265-266	80
12		C14H10N4OS	Grey	260-262	76
13		C14H10N4O2	orange	238-239	65
14		C26H18N8O2	Leady	273-274	84

RESULTS AND DISCUSSION:

Green chemistry is the need of today and light of future which gives a precious idea for the scientifically based environmental protection. chemists, researchers and pharmaceutical companies must be use to consider the principles of green chemistry while designing the reaction mechanism and selecting catalyst. by applying green chemistry procedures, we can minimize the waste materials, reduce the use of toxic chemicals , maintain the atom economy and save the environment which is heritage of our next generation.

 

The IR spectra of ethyl benzimidazole acetate (1) shows absorption bands at (1745 cm^-1) (C=O), (3062 cm^-1)           (C-H aromatic), (2966cm^-1) (C-H aliphatic), (1611 cm^-1) (C=N), (1130 cm^-1) (C-O-Csym), (1271 cm^-1) (C-O-C asy), The ultraviolet spectrum gave the highest absorption at (nm 294) λmax.

 

The IR spectra of benzimidazole acetic acid hydrazide (2) shows absorption bands at (1650 cm-1) (C=O amide), this is the frequency at hydrazide it is falling at lower frequency [18], because of existence the resonas in the hydrazide, accordingly minimize the constant power shows absorption bands at (3392cm-1) (NH), (3015cm-1) (C-H aromatic), (1586cm-1) (C=N). The ultraviolet spectrum gave the highest absorption at (nm 322) λmax.

 

 

Reaction mechanism:

 

 

Table (2): IR, ¹H NMR, ¹³C NMR and U.V spectrum data for the synthesized compounds(3-14)

Comp. No.	IR n cm-1 (KBr) ,1H NMR and 13C NMR ᵟ,ppm (DMSO)	UV (EtOH) λmax (nm)
3	IR:1631(C=N),1432(C…C Ar),1256(C-O-C asy),1179(C-O-C sym),3033(C-H aromatic),2992(C-H aliphatic),1103(N-N).	298
4	IR:1618(C=N), 1433(C…C Ar), 1214(C-O-C asy),1160(C-O-C sym), 3010(C-H aromatic), 2981(C-H aliphatic),746(C-Cl), 1096(N-N).	302
5	IR:1602(C=N),1460(C…C Ar),1229(C-O-C asy),1141(C-O-C sym),3039(C-H aromatic),2997(C-H aliphatic),3371(OH), 1055(N-N).	289
6	IR:1616(C=N),1446(C…C Ar),1221(C-O-C asy),1136(C-O-C sym),3013(C-H aromatic),2964(C-H aliphatic),1575(C=C), 1046(N-N).	314
7	IR:1604(C=N),1448(C…C Ar),1288(C-O-C asy),1159(C-O-C sym),3072(C-H aromatic),2968(C-H aliphatic)1346(C-NO2sym),1414(C-NO2asy),1103(N-N).	308
8	IR:1599(C=N),1450(C…C Ar),1221(C-O-C asy),1136(C-O-C sym), 3011(C-H aromatic),2987(C-H aliphatic),3392(OH), 1001(N-N). 1H NMR:2.49 (for DMSO),4.84 (N-CH2),7.55-7.68 (4H-Benzimidazole),7.73-7.92 (H-phenyl),8.17(N-CH-Benzimidazole),6.21 (CH-Oxadiazole),10.65 (OH). 13C NMR:55.50(N-CH2),163.08-167.178(C=N-N=C Oxadiazole), 159.93(C-OH),101.12(4C-Phenyl).	290
9	IR:1622(C=N),1468(C…C Ar),1246(C-O-C asy),1185(C-O-C sym),3040(C-H aromatic),2998(C-H aliphatic),754(C-Cl), 1085(N-N).	314
10	IR:1599(C=N),1437(C…C Ar),1236(C-O-C asy),1165(C-O-C sym),3093(C-H aromatic),2906(C-H aliphatic),1066(N-N).	292
11	IR:1611(C=N),1440(C…C Ar),1265(C-O-C asy),1124(C-O-C sym),3028(C-H aromatic),2986(C-H aliphatic),1091(N-N).	295
12	IR:1643(C=N),1500(C…C Ar),1230(C-O-C asy),1134(C-O-C sym),3008(C-H aromatic),2976(C-H aliphatic),671(C-S-C), 1001(N-N).	318
13	IR:1642(C=N),1489(C…C Ar),1222(C-O-C asy),1189(C-O-C sym),3050(C-H aromatic),2966(C-H aliphatic),1022(N-N).	288
14	IR:1636(C=N),1446(C…C Ar),1278(C-O-C asy),1196(C-O-C sym),3000(C-H aromatic),2981(C-H aliphatic),1007(N-N). 1H NMR:2.50 (for DMSO),4.92(CH2),7.22-7.41(4H-Benzimidazole),7.65(H-phenyl),8.25(N-CH-Benzimidazole). 13C NMR:56.73(CH2),104.02(C5,C5-),114.72(C2,C2-),121.38(C3,C4,C3-,C4-), 124.90(C1=,C4=),129.56(C2=,C3=,C5=,C6=),139.13(C6,C6-),143.53(C7,C7-),144.03(C1,C1-),165.06(C-CH2),167.12(C-ph).	295

 

 

Fig.1. IR spectrum of compound (10)

 

 

Fig.2. IR spectrum of compound (14)

 

Fig.3. ¹HNMR spectrum of compound (14)

 

 

Fig.4. ¹³CNMR spectrum of compound (14)

 

Fig.5. ¹HNMR spectrum of compound (8)

 

 

Fig.6. ¹³CNMR spectrum of compound (8)

 

 

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Accepted on 03.10.2018        © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(10): 4272-4276.