Synthesis and antimicrobial activity of some new quinazoline derivatives

Abstract

Some new substituted 2-Chloromethyl-4-methyl-quinazoline derivatives have been synthesised from different their chemical structures have been confirmed by IR, 1H NMR, and MASS and by elemental analysis. Investigation of antimicrobial activity of compound was done by the disk diffusion technique. Among the compound with Nitrogen containing heterocyclic compounds showed the most favourable antimicrobial activity.

Full text

Available online at www.pelagiaresearchlibrary.com
Pelagia Research Library
Der Chemica Sinica, 2014, 5(2):37-43
ISSN: 0976-8505
CODEN (USA) CSHIA5
37
Pelagia Research Library
Synthesis and antimicrobial activity of some new quinazoline derivatives
Dhaval J. Patel*, Anantkumar M. Patel and Kishor S. Pandya
Department of Chemistry, Sir P. T. Science College, Modasa, Gujarat, India
_____________________________________________________________________________________________
ABSTRACT
Some new substituted 2-Chloromethyl-4-methyl-quinazoline derivatives have been synthesised from different their
chemical structures have been confirmed by IR, 1H NMR, and MASS and by elemental analysis. Investigation of
antimicrobial activity of compound was done by the disk diffusion technique. Among the compound with Nitrogen
containing heterocyclic compounds showed the most favourable antimicrobial activity.
Keywords: Quinazolinone, antibacterial and antifungal activity.
_____________________________________________________________________________________________
INTRODUCTION
Quinazolinone and their derivatives constitute an important class of heterocyclic compounds. It is evident from
literature that Quinazolinone derivatives are known to be associated with broad spectrum of biological activity like
antibacterial
1,10
, anti-inflammatory
2,11,12
, analgesic
3
, antiviral
4
, antifungal
5
, antitubercular
6
and anticancer activity
7,13
.
MATERIALS AND METHODS
All the melting points were determined by open capillary using V-Scientific Melting Point apparatus and are
uncorrected. Purity of compound was checked by TLC on silica Gel-coated plates. IR spectra were recorded in KBr
on FTIR Prestige-211 Simadzu spectrophotometer.
1
H NMR spectra were recorded on 300 MHz Bruker using
CDCl
3
/DMSO and Mass spectra were recorded on using EI-MS mode. Elemental analysis was performed on Perkin-
Elmer Series 2400.
Scheme-I
NH
2
O
HCl NH
2
HCl
O
N
N
Cl
C
8
H
9
NO
Mol. Wt.: 135.16
C
8
H
10
ClNO
Mol. Wt.: 171.62 C
10
H
9
ClN
2
Mol. Wt.: 192.64
1-(2-Amino-phenyl)-ethanone 2-Chloromethyl-4-methyl-quinazoline
NC Cl

Dhaval J. Patel et al Der Chemica Sinica, 2014, 5(2):37-43
_____________________________________________________________________________
38
Pelagia Research Library
Scheme-II
R-Different substituent
Synthesis of 2-Chloromethyl-4-methyl-quinazoline :( DJP/001-010)
As shown in above scheme. As literature serve the synthesis 2-Chloromethyl-4-methyl-quinazoline derivatives
synthesis by the process
8
.
The 1-(2-Amino-phenyl)-ethanone was reacted with HCl gas in anhydrous condition we get Hydrochloride salt of 1-
(2-Amino-phenyl)-ethanone (a) further more reaction of them with chloro acetonitrile subjected to a intramolecular
cyclization in presence of dioxane to yield corresponding 2-Chloromethyl-4-methyl-quinazoline (b) further more
reaction with different derivatives get 2-Chloromethyl-4-methyl-quinazoline derivatives.(DJP/D101-120).All these
2-Chloromethyl-4-methyl-quinazoline derivatives were identified by IR,
1
H NMR and MASS.
Synthesis of substituted 2-Chloromethyl-4-methyl-quinazoline derivatives:
(DJP/A101-110)
General Procedure
2-Chloromethyl-4-methyl-quinazoline derivatives (0.01 mol) DJP/D101-120 and different amine derivatives (0.01
mol) and potassium carbonate(0.01) in 10 ml of N,N-Dimethyl formamide stir for 2-3 hours at 90-95°C temperature
then charge 100 ml water in to reaction mass then stir for another 1 hour and add 50ml x 2 times of
Dichloromethane for extraction then distil out solvent completely then crystallization in ether and dry material at
50-60°C.As shown in scheme-II.
Spectral Data
1. 2-Chloromethyl-4-methyl-quinazoline (DJP/D101):
IR (KBr): 3021.96 (Aromatic –C-H stretching), 2916.98 (Aliphatic stretching), 1560.62(Aromatic –C=C–
stretching), 1560.6 2(–C=N Stretching), 1396.65(–C=C– ring skeleton vibration ); 1 H NMR (CDCl
3
) ppm: 2.98
(3H,s,-CH
3
), 4.86 (2H,s,-CH
2
-), 7.63-7.68 (1H,m,ArH), 7.88-7.90 (2H,m,ArH), 8.02-8.04 (1H,d,ArH), 8.09-8.12
(1H,d,ArH); MS m/z:192.9[M
+
]
2. 4-(4-Methyl-quinazolin-2-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (DJP/D102):
IR (KBr): 3001.34 (Aromatic –C-H stretching), 1570.11 (Aromatic –C=C– stretching), 2976.26 (Aliphatic –C-H
stretching), 1362.72(Aliphatic –C-H bending), 1639.56 (–C=O stretching of carbonyl), 1570.11 (–C=N
Conjugation), 1411.94 (–C=C– ring skeleton vibration); 1 H NMR (CDCl
3
) ppm: 1.488 (3H,s,-CH
3
), 2.59-2.68
(4H,m,2-CH
2
-), 2.96 (3H,s,-CH
3
), 3.51-3.54 (4H,m,2-CH
2
-), 3.95 (2H,s,-CH
2
-), 7.59-7.647 (2H,m, ArH), 7.84-789
(1H,m,ArH), 8.02-8.10 (2H,m,ArH),; MS m/z: 343.1[M
+
],365.4 [M
+1
+Na]
3. 1-(4-Methyl-quinazolin-2-ylmethyl)-piperidine-4-carboxylic acid ethyl ester (DJP/D103):
IR (KBr): 3057.27 (Aromatic –C-H stretching), 1562.39 (Aromatic–C=C–stretching), 2951.19 (Aliphatic –C-H
stretching), 1438.94 (Aliphatic –C-H bending), 1730.21 (–C=O stretching of carbonyl), 1570.11(–C=N
Conjugation), 1438.94 (–C=C– ring skeleton vibration); 1 H NMR (CDCl
3
) ppm: 1.88-1.93 (4H,m,2-CH
2
-), 2.20-
2.27 (2H,m,-CH
2
-), 2.30-2.37 (1H,m,-CH-), 2.96 (3H, m,-CH
3
), 3.04-3.07 (2H,m,-CH
2
-), 3.67 (3H,s,-CH
3
),
3.92(2H,s,-CH
2
-), 7.58-7.62 (1H, m, ArH), 7.8-7.83 (1H, m, ArH), 8.02-8.07 (1H, m, ArH), 8.08-8.1(1H, m, ArH);
MS m/z: 314[M
+
],322 [M
+1
+Na]
4. 2-(4-Ethyl-piperazin-1-ylmethyl)-4-methyl-quinazoline (DJP/D104):
IR (KBr):3045.58 (Aromatic –C-H stretching), 1582.19 (Aromatic-C=C-stretching), 2975.21 (Aliphatic –C-H
stretching), 1448.74 (Aliphatic –C-H bending), 1710.42,( –C=O stretching of carbonyl), 1560.24 (–C=N
Conjugation), 1452.11 (–C=C– ring skeleton vibration); 1 H NMR (CDCl
3
) ppm: 1.82-1.90 (3H, m,-CH
3
), 2.62-2.71
N
N
Cl
C
10
H
9
ClN
2
Mol. Wt.: 192.64
2-Chloromethyl-4-methyl-quinazoline
K
2
CO
3
DMF N
NNH R
2-Chloromethyl-4-methyl-quinazoline derivative
s
R-NH
2

Dhaval J. Patel et al Der Chemica Sinica, 2014, 5(2):37-43
_____________________________________________________________________________
39
Pelagia Research Library
(4H,m,-2CH
2
-), 2.73-2.75 (2H,m,-2CH
2
-), 2.78-2.82 (4H,m,-2CH
2
-), 3.65 (3H,s,-CH
3
), 3.83(2H,s,-CH
2
-), 7.48-7.5
(1H, m, ArH), 7.56-7.82 (2H, m, ArH), 7.83-7.84 (1H, m, ArH); MS m/z: 271[M
+
],294 [M
+1
+Na]
5. Methyl-quinazolin-2-ylmethyl)-piperidine-4-carboxylic acid hydrazide (DJP/D105):
IR (KBr) : 3437.26, 3348.24 (–NH
2
stretching), 3061.35 (Aromatic –C-H Stretching), 1407.54 (Aromatic–C=C–
stretching), 2958.54 (Aliphatic –C-H stretching), 1379.84 (Aliphatic –C-H bending), 1670.24 (–C=O stretching of
carbonyl), 1550.86 (–C=N Conjugation), 1447.25 (–C=C– ring skeleton vibration; 1 H NMR (CDCl
3
) ppm: 1.94-
2.012.204 (4H,m,-2CH
2
-), 2.2 (2H broad singlet of –NH
2
), 2.42-3.48 (4H,m,-2CH
2
-), 2.96 (3H, m,-CH
3
), 3.62
(2H,m,-CH
2
-), 7.58-7.59 (1H,m,ArH), 7.80-7.81 (1H,s,ArH), 7.84-7.88 ; MS m/z: 300.1[M
+
], 323.1 [M
+1
+Na]
6. 4-Methyl-2-morpholin-4-ylmethyl-quinazoline (DJP/D106):
IR (KBr): 3115.14 (Aromatic –C-H stretching), 1537.32 (Aromatic –C=C– stretching), 2928.04 (Aliphatic –C-H
stretching), 1396.51 (Aliphatic –C-H bending), 15582.25 (–C=N Conjugation), 1435.52 (–C=C– ring skeleton
vibration ; 1 H NMR (CDCl
3
) ppm: 2.35-3.38 (4H,m,-2CH
2
-), 2.98 (3H,s,-CH
3
), 3.61 (2H,s,-CH
2
), 3.65-3.69
(4H,m,2-CH
2
-), 6.997-6.960 (1H,m,ArH), 7.173 (1H,s,ArH), 7.613-7.533 (2H,m,ArH) ; MS m/z: 244.2[M
+
], 261
[M
+1
+NH
3
]
7. Methyl-(4-methyl-quinazolin-2-ylmethyl)-phenyl-amine (DJP/D107):
IR (KBr): 3125.24 (Aromatic –C-H stretching), 1565.86 (Aromatic –C=C–stretching), 2928.68 (Aliphatic –C-H
stretching), 1365.87 (Aliphatic –C-H bending), 1596.35 (–C=N Conjugation), 1425.59 (–C=C– ring skeleton
vibration ; 1 H NMR (CDCl
3
) ppm: 2.31 (3H,s,-CH
3
), 2.96 (3H,s,-CH
3
), 4.61 (2H,s,-CH
2
-), 6.58-6.6 (1H,m,ArH),
6.78-6.73 (1H,m,ArH), 6.75-6.8 (2H,m,ArH), 7.57-7.58 (2H,m,ArH), 7.62-7.79 (1H,m,ArH), 8.01-8.03
(1H,m,ArH); MS m/z: 264.2[M
+
], 287 [M
+1
+Na]
8. 1-(4-Methyl-quinazolin-2-ylmethyl)-pyrrolidine-2-carboxylic acid amide (DJP/D108):
IR (KBr): 3105.47 (Aromatic –C-H stretching), 1583.46 (Aromatic –C=C–stretching), 2928.41 (Aliphatic –C-H
stretching), 1379.15 (Aliphatic –C-H bending), 1610.24 (–C=O stretching of carbonyl), 1582.25 (–C=N
Conjugation), 1445.42 (–C=C– ring skeleton vibration ; 1 H NMR (CDCl
3
) ppm: 1.52-1.53 (2H,m,-CH
2
-), 1.80-1.83
(2H,m,-CH
2
-), 2.34-3.25 (2H,m,-CH
2
-), 2.96(3H,s,-CH
3
), 3.19 (1H,m.-CH-), 3.58 (2H,s,-CH
2
-), 5.84 (2H broad
singlet of amide), 7.57-7.58 (1H,m,ArH), 7.62-7.79 (2H,m,ArH), 8.01-8.03 (1H,m,ArH); MS m/z: 371.4[M
+
],
413.4 [M
+1
+ACN]
9. 4-Methyl-2-(4-pyrimidin-2-yl-piperazin-1-ylmethyl)-quinazoline (DJP/D109):
IR (KBr): 3123.24 (Aromatic –C-H stretching), 1510.32 (Aromatic –C=C– stretching), 2943.47 (Aliphatic –C-H
stretching), 1341.83 (Aliphatic –C-H bending), 1498.42 (–C=N Conjugation), 1415.68 (–C=C– ring skeleton
vibration ; 1 H NMR (CDCl
3
) ppm: 2.49-2.58 (4H,m,2-CH
2
-), 2.98 (3H,s,-CH
3
), 3.10-3.15 (4H,m,2-CH
2
-), 3.57
(2H,m,-CH
2
-), 7.57-7.59 (1H,s,ArH), 7.6-7.68 (1H,d,ArH), 7.65-8.01 (1H,d,ArH), 8.2-8.23 (1H,m,Pyrimidine ring),
8.28-8.36 (2H,m,pyrimidine ring) ; MS m/z: 322[M
+
], 363.2 [M
+1
+ACN]
10. (2-Methyl-4-nitro-phenyl)-(4-methyl-quinazolin-2-ylmethyl)-amine (DJP/D110):
IR (KBr): 3315.75 (-N-H stretching), 3028.54 (Aromatic –C-H stretching), 1538.63 (Aromatic –C=C- stretching),
2937.35 (Aliphatic –C-H Stretching), 1351.23(Aliphatic –C-H bending), 1526.32(-N-O stretching of Nitro), 1498.42
(–C=N Conjugation), 1415.68 (–C=C– ring skeleton vibration) ; 1 H NMR (CDCl
3
) ppm: 2.96 (3H,s,-CH
3
), 3.35
(3H,s,-CH
3
), 4.36 (2H,s,-CH
2
-), 6.57 (1H,s,ArH), 7.27-7.3 (1H,d,ArH), 7.403-7.413 (2H,dd,ArH), 7.438-7.482
(1H,d,ArH), 7.484-7.524 (1H,m,ArH); MS m/z: 309.3 [M
+
], 333.3 [M
+1
+Na]
11. [(4-Methyl-quinazolin-2-ylmethyl)-amino]-acetic acid ethyl ester (DJP/D111):
IR (KBr): 3230.48 (-N-H stretching), 3104.94 (Aromatic –C-H stretching), 1534.23 (Aromatic –C=C– stretching),
2948.40 (Aliphatic –C-H stretching), 1340.86 (Aliphatic –C-H bending), 1570.29 (-C=O stretching of carbonyl),
1545.71 (–C=N Conjugation), 1417.42 (–C=C– ring skeleton vibration); 1 H NMR (CDCl
3
) ppm: 1.28 (3H,s,-CH
3
),
2.96 (3H,s,-CH
3
), 3.51 (2H,s,-CH
2
-), 4.21 (2H,m,-CH
2
-), 6.957-7.03 (1H,m,ArH), 7.135-7.214 (1H,s,ArH), 7.177
(1H,d,ArH), 7.21 (1H,d,ArH),; MS m/z: 260.4 [M
+
], 277.4 [M
+1
+NH
3
]
12. 4-[(4-Methyl-quinazolin-2-ylmethyl)-amino]-benzoic acid ethyl ester (DJP/D112):
IR (KBr): 3435.73 (-N-H stretching), 3124.94 (Aromatic –C-H stretching), 1532.43 (Aromatic –C=C- stretching),
2992.30 (Aliphatic –C-H stretching), 1326.86 (Aliphatic –C-H bending), 1667.54 (-C=O stretching of carbonyl),
1574.11 (–C=N Conjugation), 1467.21 (–C=C– ring skeleton vibration) ; 1 H NMR (CDCl
3
) ppm: 1.28 (3H,triplet,-
CH
3
), 2.98 (3H,s,-CH
3
), 4.28 (2H,s,-CH
2
-), 7.63-7.69 (1H,m,ArH), 7.7-7.72 (1H,s,ArH), 7.75-7.84 (2H,m,ArH);
MS m/z: 322.4 [M
+
], 364.4 [M
+1
+ACN]

Dhaval J. Patel et al Der Chemica Sinica, 2014, 5(2):37-43
_____________________________________________________________________________
40
Pelagia Research Library
13. 4-Methyl-2-[1,2,4]triazol-1-ylmethyl-quinazoline (DJP/D113):
IR (KBr): 3174.94 (Aromatic –C-H stretching), 1570.14 (Aromatic –C=C– stretching), 2915.68 (Aliphatic –C-H
stretching), 1341.31(Aliphatic –C-H bending), 1534.29 (–C=N Conjugation), 1446.20 (–C=C– ring skeleton
vibration) ; 1 H NMR (CDCl
3
) ppm: 2.96 (3H,s,-CH
3
), 4.89 (2H,s,-CH
2
-), 6.47-6.52 (1H,m,triazole ring), 6.543-
6.549 (1H,m,triazole ring), 6.58-6.60 (1H,m,ArH), 7.01-7.32 (1H,m,ArH), 8.02-8.14 (1H,d,ArH), 7.21(1H,d,ArH);
MS m/z: 226.1 [M
+
], 249 [M
+1
+Na]
14. 4-Methyl-2-pyrrolidin-1-ylmethyl-quinazoline (DJP/D114):
IR (KBr): 3024.86 (Aromatic –C-H stretching), 1519.27 (Aromatic –C=C- stretching), 2938.15 (Aliphatic –C-H
stretching), 1341.31 (Aliphatic –C-H bending), 1519.47 (–C=N Conjugation), 1481.62 (–C=C– ring skeleton
vibration) ; 1 H NMR (CDCl
3
) ppm: 2.12-2.23 (4H,m,2-CH
2
-), 2.41-2.45 (4H,m,2-CH
2
-), 2.98 (3H,s,-CH
3
), 4.82
(2H,s,-CH
2
-), 6.54-6.62 (1H,m,ArH), 6.651-6.589 (1H,s,ArH), 6.671-6.781 (1H,d,ArH); MS m/z: 228.3 [M
+
],
270.3 [M
+1
+ACN]
15. 4-Methyl-2-(3-methyl-piperidin-1-ylmethyl)-quinazoline (DJP/D115):
IR (KBr): 3104.64 (Aromatic –C-H stretching), 1534.23 (Aromatic –C=C– stretching), 2929.40 (Aliphatic –C-H
stretching), 1341.31 (Aliphatic –C-H bending), 1574.11 (–C=N Conjugation), 1467.21 (–C=C– ring skeleton
vibration) ; 1 H NMR (CDCl
3
) ppm: 1.85 (3H,s,–CH
3
), 2.15-2.32 (2H,m,-CH
2
-), 2.4-2.48(4H,m,2-CH
2
-), 2.49-
2.51(1H,m,-CH-), 2.51-2.57(2H,m,-CH
2
-), 2.98 (3H,s, –CH
3
), 6.957-6.976 (1H,m,ArH), 7.128-7.157 (1H,s,ArH),
7.177-7.251 (2H,d,ArH): MS m/z: 257 [M
+
], 298 [M
+1
+ACN]
16. 1-(4-Methyl-quinazolin-2-ylmethyl)-1H-pyrrole-2-carbaldehyde (DJP/D116):
IR (KBr): 3174.94 (Aromatic –C-H stretching), 1525.16 (Aromatic –C=C– stretching), 2987.24 (Aliphatic –C-H
stretching), 1347.54 (Aliphatic –C-H bending), 1570.29 (-C=O stretching of carbonyl), 1574.11 (–C=N
Conjugation), 1467.21 (–C=C– ring skeleton vibration); 1 H NMR (CDCl
3
) ppm: 2.98 (3H,s,-CH
3
), 4.87(2H,s,-CH
2
-
), 6.36 (1H,m,Pyrazole ring), 7.01 (1H,m,Pyrazole ring), 7.28 (1H,m,Pyrazole ring), 7.639-7.689 (1H,m,ArH), 7.88-
7.93 (1H,m,ArH), 8.03-8.13 (1H,d,ArH), 9.52(1H,s,aldehyde); MS m/z: 252.3 [M
+
], 275 [M
+1
+Na]
17. 4-Methyl-2-piperidin-1-ylmethyl-quinazoline (DJP/D117):
IR (KBr): 3020.63 (Aromatic –C-H stretching), 1562.39 (Aromatic –C=C- stretching), 2985.91 (Aliphatic –C-H
stretching), 1319.35 (Aliphatic –C-H bending), 1570.11 (–C=N Conjugation), 1438.94 (–C=C– ring skeleton
vibration) ; 1 H NMR (CDCl
3
) ppm: 1.83-1.93 (4H,m,2-CH
2
-), 2.28-2.27(2H,m,-CH
2
-), 2.30-2.35 (4H,m.2-CH
2
-),
3.67(3H,s,-CH
3
), 3.924 (2H,s,-CH
2
-), 7.837-7.858 (1H,m,ArH), 7.861-7.879(1H,s,ArH), 8.026-8.093(1H,d,ArH);
MS m/z: 242.3 [M
+
], 284.3 [M
+1
+ACN]
18. 2-(2, 6-Dimethyl-morpholin-4-ylmethyl)-4-methyl-quinazoline (DJP/D118):
IR (KBr): 3435.73(-N-H stretching), 3174.94(Aromatic –C-H stretching), 1543.32(Aromatic –C=C- stretching),
2929.40(Aliphatic –C-H stretching), 1341.31(Aliphatic –C-H bending), 1570.29(-C=O stretching of carbonyl),
1531.21 (–C=N Conjugation), 1415.74 (–C=C– ring skeleton vibration) ;; 1H NMR (CDCl
3
) ppm: 1.21 (6H,s,-CH
3
),
2.35-2.41 (4H,m,2-CH
2
-), 3.85 (4H,m,2-CH
2
-), 3.96 (3H,s,-CH
3
), 4.02 (2H,s,-CH
2
-), 7.564-7.587 (1H,m,ArH),
7.641-7.671 (1H,s,ArH), 7.689-7.846 (2H,d,ArH); MS m/z: 272.4 [M
+
], 314.4 [M
+1
+ACN]
19. 4-[(4-Methyl-quinazolin-2-ylmethyl)-amino]-2-trifluoromethyl-benzonitrile (DJP/D119):
IR (KBr): 3235.73 (-N-H stretching), 3154.74 (Aromatic –C-H stretching), 1553.72 (Aromatic –C=C- stretching),
2898.43 (Aliphatic –C-H stretching), 1402.21 (Aliphatic –C-H bending), 2178.46 (-CN stretching), 1498.41 (–C=N
Conjugation), 1478.34 (–C=C– ring skeleton vibration); 1H NMR (CDCl
3
) ppm: 3.68 (3H,s,-CH
3
), 4.02 (2H,s,-
CH
3
), 7.234-7.239 (1H,m,ArH), 7.349-7.486 (1H,s,ArH), 7.427-7.459(1H,d,ArH), 7.514-7.589(2H,d,ArH), 7.648-
7.841(2H,m,ArH); MS m/z: 343.3 [M
+
], 360 [M
+1
+NH
3
]
20. 2-(4-Methyl-quinazolin-2-ylmethyl)-2-aza-bicyclo [3.1.0] hexane-3-carboxylic acid amide (DJP/D120):
IR (KBr): 3435.73 (-NH
2
stretching), 3174.94 (Aromatic –C-H stretching), 1543.32 (Aromatic –C=C- stretching),
2929.40 (Aliphatic –C-H stretching), 1341.31 (Aliphatic –C-H bending), 1570.29 (-C=O stretching of carbonyl),
1428.41 (–C=N Conjugation), 1385.54 (–C=C– ring skeleton vibration); 1 H NMR (CDCl
3
) ppm: 0.487 (2H,m,-
CH
2
-), 0.491-0.648 (1H,m,2-CH-), 1.829 (2H,m,-CH
2
-),3.21 (1H,m,-CH-), 3.62 (2H,s-CH
2
-), 3.96 (3H,s,-CH
3
),
4.982 (2H,broad singlet of amide) 7.581-7.592 (1H,m,ArH), 7.723-7.789 (1H,d,ArH), 7.823-7.841 (1H,d,ArH),
8.021-8.121 (1H,m,ArH); MS m/z: 284 [M
+
], 326 [M
+1
+ACN]

Dhaval J. Patel et al Der Chemica Sinica, 2014, 5(2):37-43
_____________________________________________________________________________
41
Pelagia Research Library
Table: 1 Physical data and elemental analysis of synthesized 2-Chloromethyl-4-methyl-quinazoline derivatives (DJP/D102-DJP/D120)
N
N
NH R
Sr.
No. R
Molecular Formula M.P. (
0
C) Mol. Weight Yield
(%)
Elemental analysis Found
(Calculated)
% C % H % N
DJP/D102
N N
O
O
C
19
H
26
N
4
O
2
184-190 342.44 82 65.54
(66.64) 7.23
(7.65) 15.23
(16.36)
DJP/D103
N NEtOOC
C
18
H
23
N
3
O
2
150-154 313.39 78 67.48
(68.98) 6.75
(7.40) 12.89
(13.41)
DJP/D104
N N
C
16
H
22
N
4
125-128 270.37 75 70.58
(71.08) 8.45
(8.20) 18.96
(20.72)
DJP/D105
N NH
2
NHNOC
C
16
H
21
N
5
O 175-178 299.37 80 63.16
(64) 7.26
(7.07) 22.49
(23.39)
DJP/D106
O N
C
14
H
17
N
3
O 110-114 243.30 90 68.25
(69.11) 6.47
(7.04) 17.3
(17.27)
DJP/D107
N
C
17
H
17
N
3
124-128 263.34 68 76.51
(77.54) 5.89
(6.51) 15.48
(15.96)
DJP/D108
N
NH
2
O
C
15
H
18
F
2
N
4
O 136-139 270.33 68 65.45
(66.64) 5.98
(6.71) 19.09
(20.73)
DJP/D109
N
N
N N
C
18
H
20
N
6
204-207 320.39 62 66.45
(67.48) 6.05
(6.29) 26.12
(26.23)
DJP/D110
N
H
CH
3
N
O
2
C
17
H
16
N
4
O
2
133-136 308.33 47 66.37
(66.22) 5.12
(5.23) 15.57
(18.17)
DJP/D111
HN
O
O
C
14
H
17
N
3
O
2
89-92 259.3 77 66.45
(64.85) 6.05
(6.61) 15.12
(16.20)
DJP/D112
EtOOC N
H
C
19
H
19
N
3
O
2
122-125 321.37 53 71.37
(71.01) 5.82
(5.96) 12.57
(13.08)
DJP/D113
N
N
N
C
21
H
11
N
5
111-114 225.25 39 62.45
(63.99) 4.98
(4.92) 30.89
(31.09)
DJP/D114
N
C
14
H
17
N
3
68-71 227.3 74 73.24
(73.98) 7.45
(7.54) 18.42
(18.49)
DJP/D115
N
C
16
H
21
N
3
112-115 255.36 87 75.21
(75.26) 8.12
(8.29) 14.57
(16.46)
DJP/D116
N
H
O
C
15
H
13
N
3
O 156-160 251.28 71 71.45
(71.7) 5.05
(5.21) 16.12
(16.72)
DJP/D117
N
C
15
H
19
N
3
148-152 241.33 89 73.37
(74.65) 7.82
(7.94) 17.37
(17.41)
DJP/D118
O N
C
16
H
21
N
3
O 112-115 271.36 72 70.45
(70.82) 6.87
(7.80) 15.57
(15.49)
DJP/D119
C
N
CF
3
HN
C
18
H
13
N
4
F
3
122-125 342.32 57 62.24
(63.16) 3.82
(3.83) 16.12
(16.37)
DJP/D120
N
O
N
H
2
C
16
H
18
N
4
O 155-158 282.34 62 67.48
(68.06) 5.82
(6.43) 19.52
(19.84)

Dhaval J. Patel et al Der Chemica Sinica, 2014, 5(2):37-43
_____________________________________________________________________________
42
Pelagia Research Library
In Vitro Antimicrobial Activity
Evaluation of antibacterial and antifungal activities was done by the disk diffusion techniqu
9
. The tested compound
solution were prepared in dimethylformamide (DMF) and evaluated them for their in vitro antibacterial and
antifungal activity against Bacillus subtillis NCIM 2250, Staphylococcus aureus NCIM 2079, Escherichia coli
NCIM 2109, Aspergillus niger NICM 501 and Candida albicans NICM 7431, respectively.
Table: 2 In Vitro antimicrobial activity of 2-Chloromethyl-4-methyl-quinazoline derivatives (DJP/D102-DJP/D120)
Sr.
No. R
E-coli B-Subtillis S-Aureus S-Cerevisiae A-niger
DJP/D102
N N
O
O
+ ++ ++ + ++
DJP/D103
N NEtOOC
++ + ++ ++ +
DJP/D104
N N
+ + + ++ +
DJP/D105
N NH
2
NHNOC
+ ++ + + ++
DJP/D106
O N
+ + + ++ +
DJP/D107
N
+ + ++ ++ +
DJP/D108
N
NH
2
O
++ ++ + + +
DJP/D109
N
N
N N
++ + + + ++
DJP/D110
N
H
CH
3
N
O
2
+ + ++ + ++
DJP/D111
HN
O
O
+ ++ + + ++
DJP/D112
EtOOC N
H
+ + + ++ +
DJP/D113
N
N
N
++ ++ + + +
DJP/D114
N
++ + + + ++
DJP/D115
N
+ ++ ++ + ++
DJP/D116
N
H
O
++ + + ++ +
DJP/D117
N
+ ++ + + +
DJP/D118
O N
++ + + ++ ++
DJP/D119
C
N
CF
3
HN
++ ++ + + +
DJP/D120
N
O
N
H
2
+ ++ ++ + ++
*Effectively was classified in to three zones on the bases of the diameter of zone of inhibition
+++ : Most effective
++ : Moderate effective
+ : Slightly effective
- : Non effective

Dhaval J. Patel et al Der Chemica Sinica, 2014, 5(2):37-43
_____________________________________________________________________________
43
Pelagia Research Library
All bacteria were grown on Mueller-Hinton agar (Hi media) plates (37°C, 24 h) and fungi were grown on subouraud
dextrose agar (Hi media) plates (26°C, 48-72h). The results were established by the presence of clear zone of
inhibition around the activity compound.
RESULTS AND DISCUSSION
As many as new ten compounds were synthesized by adopting similar above procedure and then characterized by
their physical, analytical and spectral data. The detail of some of the representative compounds are given in the
experimental section. Their physical and elemental analysis data are presented in Table 1.
The entire synthesized compounds were tested for in vitro antimicrobial activity by the disk diffusion technique. The
results are summarized in Table 2 that includes the activity of reference compound Ampicillin.
The tested compound exhibited mild to moderate antibacterial activity against all three strains of bacteria. The
compound DJP/D102, DJP/D103, DJP/D105, DJP/D111, DJP/D115, DJP/D118, and DJP/D120 shows highest
activity
The antifungal activity of the compound was studied for the two pathogenic fungi. Amphotericin B was used as
reference for inhibitory activity against fungi. It was observed that compound DJP/D103, DJP/D103, DJP/D104,
DJP/D106, DJP/D107, DJP/D116, DJP/D118 had highest activity against S-Cerevisiae and DJP/D103, DJP/D108,
DJP/D109, DJP/D113, DJP/D116 and DJP/D118 tested against E-coli and showed good activity against A-Niger. It
has also observed that compound DJP/D102, DJP/D105, DJP/D108, DJP/D111, DJP/D113, DJP/D115, DJP/D120
B-Subtillis and compound DJP/D102, DJP/D103, DJP/D110, DJP/D115, DJP/D120 against S-Aureus.
CONCLUSION
The antimicrobial study revealed that substitution in the 3
rd
position of quinazoline with methyl and Nitrogen
containing heterocyclic compound produced more active compound in a series.
Acknowledgement
The authors are very much thankful to the Principal, Sir P.T. Science College, Modasa for providing necessary
facility and guidance and motivation during research work.
REFERENCES
[1] Ashis Kumar Nanda, Subarna Ganguli, Randhir Chakraborty, molecules, 2007; 12: 2413-2426.
[2] V Alagarsamy and K V Rameseshu. Pharmazie.2003, 58,233-236
[3] T.R. Jones, S.E. Webber, M.D. Varney, M.R. Reddy and K.K. Lewis, J. Med. Chem., 40, 677 (1997).
[4] N.C. Desai, N.K. Undavia, P.B. Trivedi, D. Dave, G.D. Vyas, Indian J. Exp. Biol. 36 (1998) 1280-1283.
[5] Guiping Ouyang,Peiquam Zhang, Gangfang Xu, Baoan Song, Song Yang, Linhong Jin,Wei Xue Deyu Hu,
Pinglu,zhuo chem Molecules 2006; 11: 383-392.
[6] Pattan SR, Reddy VVK, Manvi FV, Desai BG, Bhat A., Indian journal of chemistry 2006; 45B: 1771-1781.
[7] V. Murugan, N.P. Padmavathy, G.V.S. Ramasarama, S.V. Sharma, B.Suresh. Indian J. Heterocyclic Chem. 13
(2003) 143- 146.
[8] M.R. Brana, J.M. Castellano, G. Keihauer, Y. Martin and C. Redondo, Anticancer Drugs, 9, 527(1994).
[9] For testing antimicrobial agent in agar media. In: Corian V (Ed) Antibiotics in Laboratory Medicine. 5 th ed.
Williams and Wilkins, Baltimore. 1991, 1-16.
[10] G. Nagarajan, S.Kavimani Der Pharmacia Sinica, 2010, 1 (3): 109-116.
[11] Rashmi.P,LaxmivenKatesh.GandKuntal.H, Der Chemica sinica, 2011, 2(2):165-171.
[12] B.R. Dravyakar, P. B. Khedekar, Der Pharma Chemica., 2012, 4, 2, 699-706.
[13] S.Kumar, G. Mishra, P. Singh, K. K.Jha, R. L.Khosa, S.K. Gupta, et al, Der Chemica Sinica., 2011, 2, 4, 36-
58.