Synthesis and Characterization of 4-{4-(2-Methyl-4-Benzylidene-5-Oxo-Imidazol- 1-Yl)Phenyl}-6- (Substitutedphenyl)-5,6-Dihydropyrimidin-2-one and Study of their Antimicrobial Actvities

Introduction

Literature survey reveals that most of the compounds having pyrimidine nucleus possess pharmacological action^1-3. A wide spectrum of biological activities like anti-inflammatory,⁴ antibacterial,⁵ antifungal,⁶ antitubercular,⁷ analgesic and hypothermic⁸ are found to be associated with compounds having pyrimidine moiety.

Experimental

Melting points were taken in open capillary tube and were uncorrected. IR spectra (KBr) were recorded on I.R. Spectrophotometer of Buck scientific Model No. 500 and instrument used for NMR Spectroscopy was DUL 13C-1, 300 MHz and tetramethyl silane used as internal standard. Solvent used were CDCl₃ and DMSO. Purity of the compounds were checked by TLC on silica- G plates. Anti microbial activities were tested by Cup-Borer method.

Preparation of 4-benzylidene-2-methyl-1,3-oxazol-5-one (P-1).

In a 500 ml conical flask equipped with a reflux condenser a mixture of benzaldehyde (39.5g, 0.37M), acetyl glycine (29g, 0.25 M), acetic anhydride (63.5g, 0.62M) and anhydrous sodium acetate (15g, 0.183 M) was placed and heated on an electric hot plate with constant shaking. As soon as the mixture has liquefied completely, transfer the flask to a water bath and heat for 2 hours. Then add 100 ml of ethanol slowly to the contents of the flask, allow the mixture to stand overnight, filter the crystalline product with solution, wash with 25 ml of ice- cold alcohol and then finally wash with 25 ml of boiling water, dry at 100 ⁰C. The yield of almost pure oxazolone was 76 % , m.p. 150 ⁰C.Found: C(70.55%) H(4.82%) N(7.45%) , Calcd. for C₁₁H₉NO₂: C(70.58%) H(4.85%) N(7.48%).

Preparation of 1-(4-acetylphenyl)-4-benzylidene-2-methyl-imidazol-5-one (P-2)

In a 250 ml conical flask equipped with a reflux condenser a mixture of 4-benzylidene-2-methyl-1,3-oxazol-5-one(18.719g, 0.1M), 1-(4-aminophenyl)ethanone (13.51g, 0.1M), 25 ml pyridine and about one pellet of KOH was placed and was heated on sand bath for 7-8 hours. Then the mixture was poured in ice. The precipitates were collected, washed with 10% HCl and re-crystallized from ethanol. The yield of the product was 72 % and the product melts at 112 ⁰C. Found: C(74.94%)

H(5.26%) N(9.18%) , Calcd. for C₁₉H₁₆N₂O₂:

C(74.98%) H(5.30%) N(9.20%)

IR (KBr); (cm^-1)

3080(= CH-), 2960(-CH Stretch), 1705 (>C=Oimidazolone),1650 (>C=N-), 1600(>C = C<),1375(-CH₃bend), 1260(C-N).

Preparation of 4-benzylidene-1-{4-[3-(substitutedphenyl) prop-2-enoyl]phenyl}-2-methyl-imidazol-5-one (P-3).

The solution of 1-(4-acetylphenyl)-4-benzylidene-2-methyl-imidazol-5-one(3.043g, 0.01M) in absolute ethanol (50 ml),substituted benzaldehyde (0.01M) and 2% NaOH (10 ml) were added and reflixed for 10 hours. After refluxing the reaction mixture was concen trated , cooled, filtered and neutralized with dil. HCl. The solid residue thus obtained was recrystallized with suitable solvent.

Scheme 1  Click here to View scheme

 

IR (KBr);P-3a (cm^-1)

3080(= CH-), 2900 (-CH Stretch),1725 (>C=Oimidazolone) , 1675(>C=N-), 1590(>C = C<),1375 (-CH₃bend), 1260 (C-N), 700(C-Cl).

NMR ;P-3f

δ 2.501 , singlate (3H)(-CH₃), δ 3.490, singlate (3H)(-OCH₃), δ 5.631, singlate (1H) (=CH-vinylic),δ 6.660-7.902 , multiplate (14H) ( Ar-H)

8.262, singlate(1H) (-OH).

Preparation of 4-{4-[2-methyl-4-benzylidene – 5-oxo-imidazol-1-yl]phenyl}-6-(substituted phenyl)-5,6-dihydropyrimidin-2-one (P-4)

A mixture of 4-benzylidene-1-{4-[3-(substitutedphenyl)prop-2-enoyl]phenyl}-2-methyl-imidazol-5-one(0.01M) ,urea(0.01M) δand 1g. of potassium hydroxide(KOH) in 30ml of ethanol was refluxed for 3 hours. After standing over night the solid for med was collected and crystallised from acetone.

IR (KBr);P-4g (cm^-1)

3350(>NH),3240 (-OH), 3090(= CH-) , 2950(-CH Stretch ), 1720 (>C=O ) ,1600 (>C=N-), 1160 (C-N), 1500(>C = C<),1460(-CH₂-bend),1400 (-CH₃ bend), 1240 (C-O),

NMR ;P-4e

δ 1.123, doublet (2H)(-CH₂-), 2.258, triplet (1H)(-CH<), 2.490,singlate (3H)(-CH₃), 3.361, singlate (1H)( -NH-), δ 5.416, singlate (1H) (=CH-vinylic), δ 6.588-7.944, multiplate (13H) ( Ar-H), δ 8.097, singlate (1H)(-OH).

Acknowledgments

The authors are thankful to the Sheth L.H.Science College, Mansa for providing research facilities.One of the author Pankaj S. Patel is thankful to UGC. Ganeshkhind, pune.for Teacher Research Fellowship.

Table 1: Physical constant of 4-{4-[2-methyl-4-benzylidene-5-oxo-imidazol-1-yl]phenyl}-6-(substitutedphenyl)-5,6-dihydropyrimidin-2-one Click here to View table

 

Table 2: Antimicrobial activities of 4-{4-[2-methyl-4-benzylidene-5-oxo -imidazol-1-yl]phenyl}-6-(substitutedphenyl)-5,6-dihydropyrimidin-2-one

S.	Comp.	R	Zone of inhibitions in mm
No.	No.		E.coli	S.aureus	C.albicans
1	P-4a	– 4-Cl	19	20	22
2	P-4b	– 2-Cl	17	18	19
3	P-4c	– 3-OCH3, -4-OCH3	18	17	18
4	P-4d	– 2-NO2	15	15	NA
5	P-4e	– 2-OH	15	15	17
6	P-4f	– 3-OCH3, -4-OH	16	14	19
7	P-4g	– 4-OH	15	15	14
8	P-4h	– 4-N(CH3)2	15	16	18
9	P-4i	– 4-OCH3	15	NA	17
10	P-4j	– 3-OCH3, -4-OCH3,  -5-OCH3	18	17	20
11	Penicillin	–	18	20	–
12	Kanamycine	–	19	24	–
13	Baycor 25 w.p.	–	–	–	24
14	Amphotericine	–	–	–	21

 

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