Synthesis and Anti-Microbial Activity of Some Novel Mannich Base Aryl Imidazole Derivatives

 

K. Girija¹*, S. Karthika¹, Nisha Mathew²

¹Department of Pharmaceutical Chemistry, College of Pharmacy, Mother Theresa Post Graduate and Research Institute of Health Sciences,(A Govt. of Puducherry Institution), Indira Nagar, Gorimedu, Puducherry-605 006

 

ABSTRACT:

Mannich base aryl imidazole derivatives were synthesized by condensing Primary aromatic amines and Aryl aldehydes in presence of glacial acetic acid to give respective Schiffs bases, which on further treatment with Ammonium acetate and Isatin in presence of glacial acetic acid to produce aryl imidazoles followed by stirring with formaldehyde and primary amines for 1 hour in presence of ethanol to yield the corresponding Mannich bases. The purity of the synthesized compounds were checked by TLC and characterized by FT-IR, Mass spectroscopy. All the synthesized compounds were evaluated for the Anti-bacterial and Anti-fungal activity. The compounds 1a, 1b, 1c, 1e, 2a showed good antibacterial activity against Staphylococcus aureus and E.coli compared to standard Ciprofloxacin. The compounds 1a, 1c, 2a showed good antifungal activity against Candida albican compared to standard Amphotericin B.

 

 

 

INTRODUCTION:

Imidazoles are an important class of Heterocycles and studied for their biological and chemical interest¹. Imidazoles derivatives were found to have a unique place in the field of medicinal chemistry because of its wide range of biological activities like analgesic², anti-inflammatory³, anti-hemolytic, anti-cancer⁴, anti-microbial⁵, anti-spasmodic⁶, anthelmintic^7,8 and platelet aggregation inhibitor activity as per the literature review. In view of the biological significance of imidazole derivatives. The present study involves synthesize of some novel Mannich base Aryl imidazole derivatives.

 

MATERIALS AND METHODS:

EXPERIMENTAL:

Melting point were checked in open capillary tube using melting point determination apparatus and values were uncorrected. The purity of the synthesized compounds was checked by TLC using silica G as stationary phase and ethyl acetate/methanol (5:5) as mobile phase.

 

The synthesized compounds were characterized using FT-IR spectrophotometer by KBr- pellet method. The synthetic scheme to synthesize the target compounds and its physical data were shown in table1.

 

GENERAL PROCEDURE FOR THE PREPARATION OF SCHIFF’S BASE⁹

Equimolar amount (0.01M) of primary aromatic amine and aromatic aldehyde (0.01M) were transferred to 250ml RBF containing 15ml glacial acetic and refluxed for 5-6 hours.The reaction mixture was allowed to cool to give product. The completion of the reaction was monitored through thin layer chromatography. The crude products was collected and purified by recrystallization. Yield=85.95% , M.P=165º

 

GENERAL PROCEDURE FOR THE PREPARATION OF ARYL IMIDAZOLE DERIVATIVES¹⁰

Isatin (0.01M) and ammonium acetate (0.1M) were transferred in to RBF containing the schiff’s base (0.01M) and glacial acetic acid. The reaction mixture was refluxed for about 12-15 hours. The completion of reaction was monitored through TLC. The reaction mixture was poured in to 250ml of cold water to remove ammonium acetate and glacial acetic acid and it was filtered and recrystallized with absolute alcohol. Yield=65.7%, M.P=210º

GENERAL PROCEDURE FOR THE PREPARATION OF MANNICH BASE ARYL IMIDAZOLES:

Formaldehyde (5 mmol) was added slowly to 5mmol of Aryl Imidazole and 5mmol of amino compounds in 15ml of ethanol.The reaction mixture was stirred continuously for 1 hour and refrigerated for overnight. The product was filtered, recrystallized using absolute alcohol. The synthetic pathway were given in scheme 1 and its details were shown in table 1.

 

Scheme 1

(a-e)

 

Table -1 Physical data of the synthesized compounds

COMPOUND CODE	R	R1	R2
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e

 

 

 

Physico-chemical parameters and spectral characterization of the synthesized compounds:

Compound 1a: Mol wt=415.875g; Yield=65%; TLC Rf=0.602; mp=151º; logP=4.76; IR(KBr): N-H(stretch)-3354.32, C=C -1469.81, C-N- 1342.50,C=N- 1618.33, C=O-1701.27,C-Cl-754.19

 

Compound 1b: Mol wt=416.863g; Yield=67%; TLC Rf=0.600; mp=145º; logP=4.58 IR(KBr): C-H(aromatic)-3285.18,C=C-1577.38,C=N-1597.11,C-N-1338.94,C-Cl -754.19,N-H(Primary)-1577.32                 

 

Compound 1c: Mol wt=477.944g; Yield=70%; TLC Rf=0.532; mp=147; logP= 5.44IR(KBr): C-H(aromatic stretch)-3238.59, C=C-1618.33, N-H (stretch)-3385.18, C=N-1384.94, C-N-1391.75, C-Cl-718.32; MS: 477.85 m/z

Compound 1d: Mol wt=389.833g; Yield=71%; TLC Rf=0.527; mp=153º; logP=5.34 IR(KBr): C-H(aromatic stretch)-3238.59, C=C-1618.33, N-H (stretch)-3385.18, C=N-1384.94, C-N-1391.75, C-Cl -718.32

 

Compound 1e: Mol wt=464.96g; Yield=71%; TLC Rf=0.543; mp=150º; logP=5.67; IR(KBr): C-H(aromatic stretch)-3061.13, C=C-1589.43, C=N-1491.02, C-N-1329.01, N-H -3315.74, C-Cl -754.19

 

Compound 2a: Mol wt=652.743g; Yield=54%; TLC Rf=0.756; mp=178º; logP=6.20; IR(KBr): C-H(aromatic stretch)-3064.95, C=C-1597.11, S=O-1163.11, C=N-1433.43, C-N-1344.43, N-H-3358.18, -NO_{2 -}1519.96; MS: 652.75 m/z

 

Compound 2b: Mol wt= 647.660g; Yield=56%; TLC Rf=0.657; mp=179º; logP=5.91; IR(KBr): C-H(aromatic stretch)-3233.50, C=C-1615.33, S=O-1091.75, C=N-1433.43, C-N-1384.94, N-H -3385.18, -NO_2-1509.96

Compound 2c: Mol wt=554.556g; Yield=57%; TLC Rf=0.712; mp=180º; logP=4.57; IR(KBr): C-H(aromatic stretch)-3277.37, C=C-1615.33, S=O-1093.67, C=N-1469.41, C-N-1375.94, N-H-3364.32, -NO_2-1589.96

 

Compound 2d: Mol wt= 634.664g;Yield=60%; TLC Rf=0.655; mp=175º; logP= 5.90;IR(KBr): C-H(aromatic stretch)-3117.5, C=C-1615.33, S=O-1123.51, C=N-1349.41, C-N-1365.94, N-H-3350.70, -NO_2-1429.26

Compound 2e: Mol wt= 625.715g;Yield=65%; TLC Rf=0.634; mp=167º; logP=5.97; IR(KBr): C-H(aromatic stretch)-3217.37, C=C-1615.33, S=O-1083.67, C=N-1469.41, C-N-1298.94, N-H-3325.88, -NO_2-1574.22

 

Anti microbial activity:

All the synthesized compounds were evaluated for their Anti-bacterical activity against Staphylococcus aureus and E.coli and anti-fungal acitivity against Candida albicans using Agar diffusion method.  The compounds (1a, 1b, 1c, 1e, and 2a) showed significant Antibacterial activity against Staphylococcus aureus and E.coli compared to standard Ciprofloxacin and Compound (1a, 1c, 2a) exhibit significant antifungal activity against Candida albicans compared to standard Amphotericin B.

 

RESULTS AND DISCUSSION:

Mannich base Aryl imidazole derivatives were synthesized and characterized their physico-chemical properties and spectral data. All the synthesized compounds were evaluated for their Anti-microbial activity such as Antibacterial and Antifungal activity. All the synthesized compounds exhibited significant Anti-microbial activity at 150 µg/ml as compared to standard drug.

 

 

 

Table -2 Anti-bacterial activity of the synthesized compounds Anti-fungal activity of the synthesized compounds

Compound Code	Test Organism	Zone of inhibition in mm
		Std	50 µg	100 µg	150 µg
1a	S.aureus E.coli	25mm 26mm	10mm 9mm	12mm 10mm	20mm 21mm
1b	S.aureus E.coli	27mm 28mm	9mm 7mm	11mm 9mm	19mm 15mm
1c	S.aureus E.coli	28mm 29mm	14mm 11mm	19mm 15mm	22mm 19mm
1d	S.aureus E.coli	25mm 26mm	6mm 7mm	10mm 10mm	15mm 15mm
1e	S.aureus E.coli	27mm 29mm	11mm 9mm	16mm 12mm	21mm 18mm
2a	S.aureus E.coli	25mm 24mm	8mm 7mm	10mm 9mm	18mm 13mm
2b	S.aureus E.coli	23mm 25mm	9mm 5mm	11mm 11mm	17mm 13mm
2c	S.aureus E.coli	24mm 26mm	9mm 7mm	11mm 9mm	17mm 12mm
Compound Code	Test Organism		Growth of Fungal in mm
			I day	II day	III day
std	Candida albicans		7	9	13
1a	Candida albicans		6	8	12
1b	Candida albicans		6	8	9
1c	Candida albicans		7	8	11
1d	Candida albicans		6	7	8
1e	Candida albicans		6	7	7
2a	Candida albicans		8	10	10
2b	Candida albicans		6	7	8
2c	Candida albicans		6	8	9

 

 

REFERENCES:

1.     Jawaharmal , HS Lamba, Smila Narwal ,Dev Rishika, Sumit Narwal, Synthesis of novel imidazole compounds and evaluation of their antimicrobial activity. Indo Global Journal of Pharmaceutical Sciences 2(2); 2012; 147-156.

2.       Baker F, Abdel Wahat, Ghada EA, Awad Farid, A Badera, Evaluation of new imidazole based heterocycles. European J of Medicinal Chemistry 46(5); 2011; 1505-1511.

3.       Puratchikody. A, Dodle. M, Anti-norcotive and Anti-inflammatory activity and QSAR studies on substituted 4,5-diphenyl -1H-imidazoles Bioorganic and Medicinal chemistry 15; 2007; 1983-1090.

4.       Wen-Tai Li, Der-Ren Hwang, Jen-Shin Song, Ching-Ping Chen, Jiunn-Jye Chuu, Chih-Bo Hu, Heng-Liaang Lin, Chen-Lung Huang ,Chiung-Yi Huang, Huan-Yi Tseng, Hsin-Sheng Wang, Synthesis of 2-amnio -1-arylidinamnio imidazoles as orally active anti-cancer agents. Bioorganic and Medicinal Chemistry 7;1999;1913-1924.

5.       Jawaharmal , HS Lamba, Smila Narwal ,Dev Rishika, Sumit Narwal, Synthesis of novel imidazole compounds and evaluation of their antimicrobial activity. Indo Global Journal of Pharmaceutical Sciences 2(2); 2012; 147-156.

6.       L. Baskar, Papiya Mitra Mazumder, D. Sasmal and S.Ganguly, Antispasmodic effects of some n-substituted 2-methyl imidazole derivatives on guinea pig ileum. International Journal of PharmTech Research 2; Jan-Mar2010; 760-764.

7.       Lunt E, Newton C G, Smith C, Steven G P, Straw M F, Walsh R J, Warren P J, Fizames C, Lavelle F. Journal of Medicinal Chemistry (2);1987;Feb30;357-366.

8.       Bhatnagar A., Sharma P. K, Kumar N, A Review on “Imidazoles” and their Chemistry and Pharmacological Potentials. International Journal of PharmTech Research (3); 2011;268-282.

9.       Santosh Kumar, Niranjan M S, Chaluvaraju K C, Jamakhandi C M and Dayanand Kadadevar,Synthesis and Antimicrobial Study of Some Schiff Bases of Sulfonamides. Journal of Current Pharmaceutical Research (01); 2010; 39-42.

10.    Satyajit Dutta, Synthesis and Anthelmintic activity of some novel 2-substituted-4,5-diphenyl imidazole Acta Pharma (60);2010;229-235.

 

 

 

 

Received on 10.07.2014                Modified on 20.07.2014

Accepted on 01.08.2014                © RJPT All right reserved