ISSN 2319-7625 (Online) (An International Research Journal), www.chemistry-journal.org
Synthesis and Antimicrobial Activities of Some
1-[6-(substituted phenyl)pyrimidine-2-amine-4-yl]-
5-phenyl-1 H –Tetrazole
S. S. Yadav, H. N. Yadav and Vijay Kant Yadav
Department of Applied Sciences and Humanities. Lucknow Institute of Technology Lucknow, U. P., INDIA.
email: drshiv1980@rediffmail.com.
(Received on: November 17, 2015)
ABSTRACT
Substituted 1-[6-(substitutedphenyl)pyrimidine-2-amine-4-yl]-5-phenyl-1H-Terazole were synthesized by reacting the chalcones with guanidine nitrate in ethanol in presence of sodium hydroxide. The chemical structure were confirmed by means 1H NMR, Mass spectra and elemental analysis. The compound were screened
antimicrobial activity. Tetrazoles are important functionality with wide ranging application in pharmaceutical and material sciences and appealing ligands in coordination chemistry.
Keywords: Tetrazole , Pyrimidine , Antimicrobial Activity.
INTRODUCTION
Derivatives of imidazole, pyrazole, pyrimidine and isoxazole have played a crucial role in the History of heterocyclic chemistry and been used extensively as important pharmacophores and synthons in the field of organic chemistry and drug designing. Owing to their versatile chemotherapeutic importance, a significant amount of research effort has been focused on these nuclei. Benzimidazole derivatives have evoked considerable attention in recent years as these are endowed with a wide range of pharmaceutical activities like antifungal1, antihypertensive2, antioxidant3 cardiotonic4 antithrombotic5, HIV –IPR inhabitor6
IL-l inhibitor7, anticonvulsant8, antihepatitis B and C virus activity9 etc. The pyrazoline
nucleus is a ubiquitous feature of pharmacological interest and has been proven to be fertile source of medicinal agent such as cytotoxic10 antibacterial11 antiamoebic12, 5-α reductase
inhivitor13 , cyclooxygenase –ll(COX-llSS)14, antiproliferative15 and anticancer16. Pyrimidine
immunodilator19, antifoliate20 antiviral21 pyrimidine derivates have activities like tyrosine
Kinase inhibitors22 ,COX-2 inhibitor23, calcium channel blockers plus antihypertensive24 and
also activities against Y181C HIV –l mutant strain25, isoxazoles are widely investigated for
therapeutic use like antiepileptic26, PPAR-δ, agonist27 acetylcoline-esterase inhibitor28, anti –
inflammatory29 acrosin inhibitor and antifugal activates30 . etc.
EXPERIMENTAL
Melting points were determined in open capillaries and were uncorrected. Reactions were monitored by thin layer chromatography using silica gel-G as adsorbent using benzene: ethylacetate (9:1) as eluent. 1H NMR spectra (DMSO-d6) were taken a Varian mercury
spectrometer (model YH-300 FT NMR) using TMS as internal standard and chemical shift are expressed in δ ppm. Mass spectra were taken on Jeol sx-102/PA-6000(EI) spectrometer.
CHEMISTRY
Compounds were prepared as shown in scheme -1. Chalcones (1 a-d) was cyclized using guanidine nitrate in absolute alcohol and refluxed for 1 hr.10% NaOH was added to the reaction mixture and refluxing continued for 8 hr. to form Substituted 1-[6-(substitutedphenyl) pyrimidine-2-amine-4-yl]-5-phenyl-1H-Terazole (2 a-d).
General procedure for the synthesis of 1-[6-(substituted phenyl)pyrimidine-2-amine-4-yl]-5-phenyl-1 H –Tetrazole
Chalcone (2.48 g ,0.01 mole) and guanidine nitrate (1.22g, 0.01) were dissolved in absolute alcohol and refluxed for 1 hr. 10 % NaOH solution was added to the reaction mixture and refluxing continued for 8 hr. The reaction mixure was cooled and poured on crushed ice to get a light brown coloured product(2 a-d), which was purified by recrystallization from ethanol.
1-[6-( phenyl )pyrimidine-2-amine-4-yl]-5-phenyl-1 H –Tetrazole (2a)
Yield 77 % , m. p.202 0C. 1H NMR (DMSO) δ ; 7.8-7.12 (m,10H, Ar-H), 6.38
(s,2H,NH2). Anal. For C18H14N6 Cal. (found) % ; C 68.77(68.78) H 4.48(4.98) N 26.73(76.75).
MS : (m/z) : 314(M+).
1-[6-( 4-methoxyphenyl )pyrimidine-2-amine-4-yl]-5-phenyl-1 H –Tetrazole (2b)
Yield 74 %, m. p.260 0C. 1H NMR (DMSO) δ ; 7.91-7.32 (m,9H, Ar-H), 6.49
(s,2H,NH2), 3.47(s,3H,OCH3). Anal. For C19H16N6O Cal. (found) % ; C 66.26(66.27) H
4.68(4.65) N 24.40(24.41). MS : (m/z) : 344(M+).
1-[6-(4-dimethylamino phenyl )pyrimidine-2-amine-4-yl]-5-phenyl-1 H –Tetrazole (2c)
Yield 73 % , m. p.236 0C. 1H NMR (DMSO) δ ; 7.9-7.28(m,9H, Ar-H), 6.36
(s,2H,NH2,), 2.84(s,6H,N(CH3)2. Anal. For C20H19N7 Cal. (found) % ; C 67.20.(67.22) H
1-[6-(3-nitro phenyl )pyrimidine-2-amine-4-yl]-5-phenyl-1 H –Tetrazole (2d)
Yield 68 %, m. p.242 0C. 1H NMR (DMSO) δ ; 7.9-7.41 (m,9H, Ar-H), 6.29
(s,2H,NH2). Anal. For C18H13N7O2 Cal. (found)%; C 60.16(60.17) H 3.64(3.62) N 27.28
(27.29). MS : (m/z) : 344(M+)
C2H5OH Guanidine
N N
N N
N N N
N N
O
N
NH2
R3
R2
R1
R4
R1
R2
R3
R4
2a R1=R2=R3=R4=H, 2b R1=R2=R3=H, R4=OCH3 2c R1=R2=R3=H,R4=N(CH3)2 2d R1=R2=R4=H,R3=NO2
1a-d
2a-d
BIOLOGICAL EVALUATION
Evaluation of Antimicrobial Activity
Table 1- Antibacterial and Antifungal data of compound (2a-d)
RESULTS AND DISCUSSION
Antimicrobial Activity
The in-vitro antimicrobial activity of compounds (2a-d) were determined by agar plate method .The results of which are summarized in table 1. The antimicrobial data in table 1 clearly showed that the nitrophenyl, dimethylaminophenyl groups is by for the most active substituted phenyl group. The methoxyphenyl group generally confers weak antimicrobial activity. Phenyl substitution are weakly active to inactive among the synthesized compounds. Compounds 2b,2c showed good activity against S. aureous and E.coli. The compounds 2a and 2d exhibit promising activity against C. albicans and A. niger. However, the compounds were less active in comparison to Ciprofloxacin and Griseofulvin (standard Durgs).
CONCLUSION
In conclusion, the results of this investigation revealed that the observed increase in antimicrobial activities are attributed to the presence of 3-NO2 , 4-N(CH3)2, 4-OCH3, in
phenyl ring at 6- position of pyrimidine ring of synthesized compounds containing tetrazole. it is clear that the comparative evaluation of active compounds will required further studies; the data reported in this article may be helpful guide for the medicinal chemist who are working in this area.
ACKNOWLEDGEMENT
The SSY, HNY and VKY are thankful to the Head, Department of Applied Sciences and Humanities, Lucknow Institute of Technology, Lucknow for providing laboratory facilities and to the Director, CDRI, Lucknow for providing spectral data and analytical data.
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