Synthesis, Characterization of Benzimidazole Derivatives carrying Pyridine Moiety

 

K. Durga Prasad¹, M. Sandhya Rani²*, D. Anusha²

¹Natco Research Centre, Sanath Nagar, Hyderabad-500018

²Department of  Pharmaceutical Chemistry, Pulla Reddy Institute of Pharmacy,

Gummadidala, Sangareddy, Telangana-502110

*Corresponding Author E-mail: sandhya.madala@gmail.com

A new series of 1-methyl-2{[(3,4,5- tri substituted pyridine2-yl) methyl] sulfanyl}-5-nitro-1H-benzimidazoles 3a-3b were synthesized by coupling 1-methyl-2-mercapto-5-nitro-1H-benzimidazole 1 with various pyridine derivatives 2a-2b in the presence of  a base at room temperature, Upon further oxidation of these Benzimidazole derivatives 3a-3b in presence of MCPBA gives 1-methyl-2{[(3,4,5- tri substituted pyridine2-yl) methyl] sulfinyl}-5-nitro-1H-benzimidazoles 4a-4b.  The group frequencies of IR and NMR spectra were assigned.

 

 

INTRODUCTION:

Most of the currently used proton pump inhibitors for ulcer treatment¹, antihistaminic agents² are chemically benzimidazole moiety coupled with various pyridine derivatives,

 

The basic skeleton benzimidazole posses multiple activities; S-substituted 4,6-dibromo-and  4,6-dichloro-2-mercapto benzimidazoles have activity against Anti protozoal, Antibacterial activities³; A number of methods have been reported for the synthesis ofbenzimidazoles and its derivatives^4,5, moreover the influence of the substitution at 1^st, 2^nd and 5^th positions of benzimidazole ring is very important for pharmacological activity, by taking into the consideration of chemical moiety of existing PPI’s in the market, we have designed some Novel 1-methyl-2-Mercapto-5-nitro-1H- benzimidazole derivatives 3(a-b), 4(a-b) by coupling with various pyridine derivatives in the presence of a base at room temperature.

 

MATERIAL AND METHODS:

Chemicals and reagents:

All chemicals used were purchased from Sigma-Aldrich and E-Merck chemical company, Melting points of all benzimidazoles were determined in open glass capillaries on Mettler FP51 apparatus and are uncorrected. IR spectra (KBr, 4000-400cm^-1) were recorded on AVATAR-300 Fourier transform spectrophotometer. INSTRUM AV 300 NMR spectrometer was used for recording NMR spectra operating at 500 MHZ for ¹H spectra and 125.46 MHZ for ¹³C spectra in Deutereated chloroform (CDCl₃) solvent using Tetramethylasilane (TMS) as internal standard.

 

Experimental setup

General procedure^6-8 for synthesis of 1-methyl-2{[(3, 4, 5- tri substituted pyridine2-yl) methyl] sulfanyl}-5-nitro-1H-benzimidazoles

1-methyl-2-mercapto-5-nitro-1H-benzimidazole was condensed with three different pyridine derivatives in the presence of methanol and sodium hydroxide as a solvent at 10-15⁰c for 1hr. The reaction was monitored time to time by TLC. All the synthesized compounds were recrystallized by methanol.

 

1-methyl-2{[(3, 4, 5 – trisubstituted pyridine2-yl) methyl] sulfanyl}-5-nitro-1H-benzimidazole derivatives were treated with m-chloroperbenzoicacid [MCPBA] in presence of methanol and methylene chloride at 0-3⁰c for 3hrs. The reaction was monitored time to time by TLC. All the synthesized compounds were recrystallized by Isopropylether (IPE).

 

 

 

 

 

 

 

 

 

 

 

 

 

Table I: Characterization data of Synthesized compounds

Compd	R1	R2	R3	% yield	Mol. Formula (Mol. Wt)	m.p (oC)
3a	-CH3	-OCH3	-CH3	71.22	C17H18N4O3S	201.7-203.9
3b	-CH3	-OCH2 CF3	H	84.78	C17H15N4O3SF3	214-218
4a	-CH3	-OCH3	-CH3	73.25	C17H18N4O4S	254-268
4b	-CH3	-OCH2 CF3	H	81.32	C17H15N4O4SF3	216-219

 

 

RESULTS AND DISCUSSION:

COMPOUND I (MMNB-OMZ SULPHIDE) 1-methyl, 2-{[(3, 5­-dimethyl 4-methoxy) pyridine 2-yl] methylsulfanyl}5-nitro1H-benzimidazole:

Pale brown solid; M.P (201.7-203.9^oC); % yield (82%); Rf value(0.44); FTIR (KBr, 4000-400cm^-1); 1523.9(Ar-NO_{2 str.}); 2943.2(C-H _str. Alkanes); 1568.8(C=N _str.); 2363(C=C str.)H¹ NMR(500 MHZ, CDCl₃, δ,ppm): 7.2-8.5(2s,2d,4H), 4.84(s,1H), 3.75(S,3H),2.2-2.4(s,6H); ¹³CNMR(400MHZ,δ,ppm): 11.3, 13.2, 30.4, 37.2, 59.9, 107.9, 114.4, 117.8, 125.1, 125.7, 140.9, 142.7, 143.3, 149.2, 153.1,157.1,164.1; m/z 359.27(M⁺).

 

Compound II (MMNB-LNP SULPHIDE) 1-methyl, 2-{[(3-methyl4-(2, 2, 2-triflouro ethoxy) pyridine 2-yl) methyl] sulfanyl}5-nitro1H-benzimidazole:

Pale brown solid; M.P (214-218^oC); % yield (80%); Rf value(0.68); FTIR (KBr, 4000-400cm^-1); 1524.5(Ar-NO_{2 str.}); 2949.7(C-H _str. Alkanes); 1474(C=N _str.); 3131.4(C=C str.); 1056.8( C-F); 1343.9(C-O str). H¹  NMR(500 MHZ, DMSO-D6, δ,ppm): 7.2-8.5(2s,2d,4H), 4.84(s,1H), 3.75(S, 3H), 2.2-2.4(s, 6H);  ¹³C NMR (400 MHZ, δ, ppm):10.2,30.4,36.8,64.1, 64.5,64.8,65.2, 107.0,109.8,113.2, 117.4,119.9,122.4, 125.1, 141.2, 141.9, 142.5, 147.9, 154.6, 157.0, 161.1; m/z 413(M⁺).

 

COMPOUND III (MMNB-OMZ SULPHOXIDDE) 1-methyl 2-{[(3, 5­-dimethyl 4-methoxy) pyridine 2-yl]Methylsulfinyl} 5-nitro1H-benzimidazole: Pale brown solid; M.P (214-218^oC); % yield (80%); Rf value(0.68); FTIR (KBr, 4000-400cm^-1); 1524.5(Ar-NO_{2 str.}); 2949.7(C-H _str. Alkanes); 1474(C=N _str.); 3131.4(C=C str.); 1056.8( C-F); 1343.9(C-O str).H¹ NMR(500 MHZ, DMSO-D6, δ,ppm): 7.2-8.5(2s,2d,4H), 4.84(s,1H), 3.75(S, 3H), 2.2-2.4(s, 6H); ¹³C NMR(400 MHZ,δ,ppm):11.3,13.2,30.4,37.2,59.9,107.9,114.4, 117.8,125.1,125.7,140.9,142.7,143.3, 149.2,153.1, 157.1,164.1,154.6,157.0,161.1; m/z 375(M⁺).

 

COMPOUND IV (MMNB-LNP SULPHOXIDE) 1-methyl, 2-{[(3-methyl4-(2,2,2-triflouro ethoxy) pyridine              2-yl)methyl]sulfinyl}5-nitro1H-benzimidazole; Pale brown solid; M.P (214-218^oC); % yield (80%); Rf value(0.68); FTIR (KBr, 4000-400cm^-1); 1524.5(Ar-NO_{2 str.}); 2949.7(C-H _str. Alkanes); 1474(C=N _str.); 3131.4(C=C _str.); 1056.8( C-F); 1343.9(C-O _str). H¹ NMR(500 MHZ, CDCL₃, δ,ppm): 6.75-8.52(d,5H), 5.08(q,2H), 4.38-4.44(S,1H), 3.68(s,6H); 2.6(S,3H); ¹³CNMR(400MHZ,δ,ppm): 10.2, 30.4, 36.8, 64.1, 64.5, 64.8, 65.2, 107.0, 109.8, 113.2, 117.4, 119.9, 122.4, 125.1, 141.2,141.9,142.5,147.9,154.6,157.0,161.1; m/z 429(M⁺).

 

ACKNOWLEDGEMENT:

With pride and immense pleasure and profound sense of gratitude we take this opportunity to express our sincere thanks to Dr. K. Durga Prasad, Vice President, Natco Research Centre, Sanathnagar, Hyd. for his support throughout the project, spectral data.

 

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

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Received on 21.08.2017         Modified on 19.01.2018

Accepted on 22.02.2018         © AJRC All right reserved