Synthesis and Antibacterial activity of some 4,5-disubstituted-6-Methyl-1,2,3,4- Tetrahydropyrimidin-2(1H)-one derivatives

Divyang H. Shah *and Prof. (Dr.) Dhrubo Jyoti Sen
Shri Sarvajanik Pharmacy College, Gujarat Technological University, Arvind Baug, Mehsana-384001, Gujarat
Corresponding Author: Divyang H. Shah E-mail: [email protected]
Received: 28 May 2012 Accepted: 11 June 2012
Citation: Divyang H. Shah and Prof. (Dr.) Dhrubo JyotiSen “Synthesis and Antibacterial activity of some 4,5–disubstituted–6–Methyl-1,2,3,4-Tetrahydropyrimidin–2 (1H)- one derivatives”, Int. J.Drug Dev. & Res., April-June 2012, 4(2): 330-335
Copyright: © 2012 IJDDR, Divyang H. Shah etal. This is an open access paper distributed under thecopyright agreement with Serials Publication, whichpermits unrestricted use, distribution andreproduction in any medium, provided the originalwork is properly cited.
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Eight new 4,5-disubstituted-6-methyl-1,2,3,4- tetrahydropyrimidin-2(1H)-one derivatives are synthesized by three steps. All synthesized compounds are confirmed by IR, Mass and H1NMR. Antibacterial activity is carried out by filter disc method. All test compounds are active against the gram negative E.coli and in higher concentration active against the gram positive S.aureus. Compounds 6b and 6e are more potent among synthesized series.

Key words

Biginelli reaction, Tetrahydropyrimidines, Zone ofinhibition, Gram +ve bacteria, Gm –ve bacteria


The treatment of many infectious diseases arechallenging due to resistance to antimicrobial agents.The emergence of resistance among bacteria to awide variety of structurally unrelated antibacterialagents such as 6-lactams, macrolides, tetracyclinesand fluoroquinolones as well as selected dyes anddisinfectants has become a serious public healthconcern so makes it necessary to continue the searchfor new antibacterial agents.
In recent scenario heterocycles plays a major rule indrug synthesis. In that respect pyrimidine plays asignificant rule among other heterocycles. From theliterature survey, in recent years 4,5-disubstituted-6-methyl-1,2,3,4-tetrahydropyrimidin-2(1H)-one haveattracted considerable interest because of theirtherapeutic and pharmacological properties. Severalof them have been found to exhibit a wide spectrumof biological effects including antimicrobial,antitumour, antiviral, antihypertensive, calciumchannel blocker, alpha-1a adrenergic antagonist, neuropeptide antagonist. So it was planed tosynthesize a novel series of 4,5-disubstituted-6-methyl-1,2,3,4-tetrahydropyrimidin-2(1H)-onederivatives and to check their activity asantimicrobial activity.1-2


The entire chemicals were supplied by S.D. Finechem. (Mumbai), Finar chem. Ltd (Ahmedabad) andLoba Chemie. Pvt. Ltd. (Mumbai). Melting points

Scheme of Synthesis

were determined by open tube capillary method andare uncorrected. Purity of compounds was checkedby thin layer chromatography (TLC) on silica gel G insolvent system hexane-ethyl acetate (1:2), the spotswere located under iodine vapours or UV light. IRspectra of all compounds were recorded on FT-IR8400S Shimadzu spectrophotometer using KBr.Mass spectra were obtained using 2010EV LCMSShimadzu instrument.

General Procedure for Ethyl 4-(4-substitutedphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 1-4

0.1mole (6gm) of urea, 0.1mole, substitutedbenzaldehyde and 0.1mole (12.6ml) of ethylacetoacetate were taken and refluxed with 2-3 dropsof Conc. HCl and sufficient quantity of ethanol at 70-80ºC temperature for 4-5 hrs. It was then allowed tocool and after addition of water, precipitate was obtained, which was filtered and recrystallized fromethanol. (4a-4b)

General procedure of 4-(4-substitutedphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-5-carboxylic acid 5

Ethyl-4-(4-substitutedphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate(0.01mole) was refluxed with 50 ml of 10% alcoholicNaOH for 1 hr and after cooling the reaction mixture and acidification with Conc. HCl precipitate of acidwas obtained, which was filtered, washed with waterand recrystallized from ethanol. (5a-5b)

General Procedure of Preparation of 4,5-disubstituted-6-methyl-1,2,3,4-tetrahydropyrimidin-2(1H)-one derivatives5

4-(4-substitutedphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-5-carboxylic acid (0.01mole)was refluxed with 15ml of thionyl chloride for30mins. Unreacted thionyl chloride was removed byheating the reaction mixture on water-bath. Aftercooling the acid chloride product, 3 to 4 times ofdifferent amines and ethanol as reaction medium was added. Reaction mixture was stirred for 5 hrs thenadded cold water to the reaction mixture. Precipitatewas obtained, which was filtered and recrystallizedfrom ethanol. (6a-6h)

Physical Characteristics of SynthesizedCompounds


Spectral data of synthesized compounds


Spectral data of synthesized compounds


Antibacterial Activity6,7

The microbiological assay is based upon acomparison of inhibition of growth of microorganismsby measured concentrations of testcompounds with that produced by knownconcentration of a standard antibiotic ciprofloxacinusing microorganisms Staphylococcus aureus(MTCC No. 96) and Escherichia coli (MTCC No.521).
A filter paper sterilized disk saturated with measuredquantity of the sample was placed on plate containingsolid bacterial medium (nutrient agar broth) whichhas been heavily seeded with spore suspension of thetested organisms. After inoculation, the diameter ofthe clear zone of inhibition surrounding the samplehas been taken as measure of inhibitory power ofsample against the particular test organisms.

Results and Discussion

4,5-disubstituted-6-methyl-1,2,3,4-tetrahydropyrimidin-2(1H)-one derivatives havebeen synthesized by 3 steps. Reactions have beenmonitered by TLC. All synthesized derivatives havebeen confirmed by IR, Mass and H1NMR.Antibacterial activity has been carried out by thefilter disk method. All compounds showed activityagainst the gram negative E.coli and in higherconcentration activity has been found against grampositive S.aureus.

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