SYNTHESIS OF 2-SUBSTITUTED QUINAZOLINONES AND THEIR
PHARMACOLOGICAL ACTIVITY
Ganesh A1*, Parameshwar Pabba2, Vidyasagar M2
1.Associate Professor, Department of Pharmaceutical Chemistry, Procadence Institute of
Pharmaceutical Sciences, Rimmanaguda, Gajwel, Medak dist, Telangana.
2. Joythishmathi Institute of Pharmaceutical Sciences, Timmapur, Karimnagar,Telangana.
Author for Correspondence
Ganesh Akula,
Associate Professor
Department of Pharmaceutical Chemistry,
Procadence Institute of Pharmaceutical Sciences,
Rimmanaguda, Gajwel,
Medak dist, Telangana.
E-mail:akulaganesh@gmail.com
Phone no: +91-9951198726
ABSTRACT:
Quinazolinone is a heterocyclic chemical compound. There are two structural isomers, 2-quinazolinone
and 4-quinazolinone, with the 4-isomer being the more common. Literature survey reveals that in recent
years several quinazolinone derivatives have been synthesized and reported to possess varied biological
and pharmacological properties. They are found to be useful as anti-bacterial, analgesic, antiinflammatory, anti-fungal, antimalarial, antihypertensive, CNS depressant, anticonvulsant, antihistaminic
& local anaesthetic, anti-parkinsonism, antiviral and anticancer agents. In the present work, synthesis of 2substituted quinazolinone derivatives were carried out and these compounds were evaluated for their
pharmacological activities especially anti-microbial activity. These compounds showed pharmacological
activities in comparison with the standard.
KEY WORDS:
Quinazolinone, Anti-bacterial, Anti-fungal, Mannich reaction.
INTRODUCTION:
Quinazoline or 1,3-diazanaphthalene is a bicyclic compound made up of two fused six-membered
simple aromatic rings consisting of pyrimidine system fused with benzene having broad spectrum of
medicinal values. The many derivatives of quinazoline system known so far, keto-quinazolines also
called as Quinazolinone, are the most important compounds. A number of alkaloids having
quinazoline or quinazolinone moiety in their structure have been isolated from different plants.
Quinazolinone derivatives were carried out according to scheme-1 and these compounds were
evaluated for their pharmacological activities especially anti-microbial activity. These compounds
showed pharmacological activities in comparison with the standard drugs.
MATERIALS AND METHODS:
Keeping in view an array of applications, it has been felt worthwhile to synthesize some new substituted
quinazolinone derivatives as such reactions are not reported so for and also to screen for the anti-microbial
activity. The synthesis of title compounds could be achieved by the Scheme-I.
Collection of the chemicals: All chemicals are of analytical grade and are brought from Sd.fine Chem.
Ltd.
Experimental Procedure:
Synthesis of 2-phenyl-4(3H)-Quinazolinone (compound a): Anthranilic acid (0.1mole) was dissolved in
100ml of methanolic potassium hydroxide. Then gradually added aryl amide (Benzamide, 0.1 moles).the
contents were refluxed for 3 hours and were cooled to room temperature. The reaction mixture was
filtered and washed with methanol and dried. The dried crude product was recrystallized from methanol to
get the compound.
Synthesis of 2-methyl-4(3H)-Quinazolinone (compound b):Anthranilic acid (0.1mole) was dissolved in
100ml of methanolic potassium hydroxide. Then gradually added alkyl amide (Acetamide, 0.1 moles).the
contents were refluxed for 3 hours and were cooled to room temperature. The reaction mixture was
filtered and washed with methanol and dried. The dried crude product was recrystallized from methanol to
get the compound.
Synthesis of 4(3H)-Quinazolinone (compound c): Anthranilic acid (0.1mole) was dissolved in 100ml of
methanolic potassium hydroxide. Then gradually added alkyl amide (Formamide, 0.1 moles).the contents
were refluxed for 3 hours and were cooled to room temperature. The reaction mixture was filtered and
washed with methanol and dried. The dried crude product was recrystallized from methanol to get the
compound.
3-[(dialkylamino)methyl]-2-substituted-4(3H)- Quinazolinone (compound a1-c1): 2-substituted4(3H)-Quinazolinone (0.01 mole) was taken in 5 ml of 95% ethyl alcohol and slurry was formed. To this
gradually added 37% formaldehyde (0.02mole) and dialkyl amine (dimethyl amine, 0.01 moles). A clear
solution was obtained. To this solution 30 ml of 95% ethyl alcohol was added and it was concentrated by
evaporation on a hot plate until a semisolid was formed. This was purified by re crystallization with
sufficient ethanol. Following compounds were prepared by using above procedure: 3-[(dimethyl amino)
methyl]-2-phenyl-4(3H) - Quinazolinone (compound a1), 3-[(dimethyl amino) methyl]-2-methyl-4(3H)Quinazolinone (compound b1) and 3-[(dimethyl amino) methyl] -4(3H)- Quinazolinone (compound c1)
3-[(diarylamino)methyl]-2-substituted-4(3H)-Quinazolinones(compound a2- c2): 2-substituted-4(3H)Quinazolinone (0.01 mole) was taken in 5 ml of 95% ethyl alcohol and slurry was formed. To this
gradually added 37% formaldehyde (0.02mole) and diaryl amine (diphenyl amine, 0.01 moles). A clear
solution was obtained. To this solution 30 ml of 95% ethyl alcohol was added and it was concentrated by
evaporation on a hot plate until a semisolid was formed. This was purified by re crystallization with
sufficient ethanol. Following compounds were prepared by using above procedure: 3-[(diphenyl amino)
methyl]-2-phenyl-4(3H) - Quinazolinone (compound a2), 3-[(diphenyl amino) methyl]-2-methyl-4(3H) Quinazolinone (compound b2) and 3-[(diphenyl amino) methyl] -4(3H) - Quinazolinone (compound c2)
Compound a: R= C6H5, Compound a1: R1= R2= CH3, a2: R1= R2= C6H5
Compound b: R= CH3, Compound b1: R1= R2= CH3, b2: R1= R2= C6H5
Compound c: R= H, Compound c1: R1= R2= CH3, c2: R1= R2= C6H5
ANTI-MICROBIAL ACTIVITY:
The synthesized compounds were tested against Bacillus Subtilis, Staphylococcus aureus,
Escherichia coli, Aspergillus niger and Candida albicans. The glass Petri dishes were cleaned and
sterilized. The nutrient agar media is mixed with sufficient amount of distilled water and sterilized.
The media was allowed to solidify at room temperature. A sterile borer was used to prepare four
cups of 8mm diameter in the agar media. A test solution of synthesized compounds was prepared
at a concentration of 100µg/ml and 150 µg/ml with DMF. A solution of standard drug was
prepared at the same concentration. Accurately measured (0.1 ml) solution of test and standard
samples were added to cups with micropipette. All Petri dishes were incubated at 37±1ºC for 24
hrs. The solvent DMF was used as blank. The diameter of zone of inhibition was measured and
recorded and shown in table 2.
RESULTS AND DISCUSSION:
Various New Derivatives of Quinazolinone were synthesized from Quinazolinone by Mannich
reaction with 37% Formaldehyde, dimethyl amine/diphenyl amine and Ethanol. For the synthesis
of Quinazolinone, Anthranilic acid was taken as a starting material, condensing with the amide and
methanolic Potassium hydroxide. Physical characterization of the title compounds were given in
the table-1.
Antimicrobial Activity:
Table-2 showing the data on antimicrobial activity of the compounds could reveal that all the six
compounds could exhibit a moderate to potent activity, against both Gram positive and Gramnegative bacteria. Among the tested compounds, Compound a1, b1 & c1 was found to show an
appreciable zone of inhibition against both Gram positive and Gram negative bacteria and its
activity was found to be comparable to that of the standard drug Norfloxacin and Fluconazole.
Table-1: Physical Characterization of the title compounds:
S.No.
Compound
R
R1
R2
M.P
(0C)
% Yield
Molecular
Formula
Molecular
weight
1.
a
-C6H5
-
-
115
78.81
C14H10N2O
222
2.
b
-CH3
-
-
110
77.00
C9H8N2O
160
3.
c
-H
-
-
105
78.76
C8H8N2O
146
4.
a1
-
-CH3
-CH3
103
77.00
C17H17N3O
279
5.
a2
-
-C6H5
-C6H5
105
75.00
C27H21N3O
403
6.
b1
-
-CH3
-CH3
138
79.00
C12H15N3O
217
7.
b2
-
-C6H5
-C6H5
150
77.00
C22H19N3O
341
8.
c1
-
-CH3
-CH3
154
92.27
C11H13N3O
203
9.
c2
-
-C6H5
-C6H5
102
78.00
C21H17N3O
327
Table-2: Anti-microbial activity of compounds a1 to c2 and Standard drugs
Cup-plate diffusion method (Zone of inhibition in mm)
Anti-bacterial activity
Compound
B.Subtilis
S.Aureus
Anti-fungal activity
E.Coli
A.Niger
C.Albicans
100
150
100
150
100
150
100
150
100
150
µg/
µg/
µg/
µg/
µg/
µg/
µg/
µg/
µg/
µg/
ml
ml
ml
ml
ml
ml
ml
ml
ml
ml
Norfloxacin
22
25
22
25
22
25
-
-
-
-
Fluconazole
-
-
-
-
-
-
22
24
16
18
a1
21
22
18
20
17
19
18
20
14
16
a2
15
18
16
18
15
17
-
15
-
12
b1
18
20
17
19
20
21
15
19
10
12
b2
-
15
-
14
-
-
10
11
10
12
c1
20
21
17
19
18
20
16
18
11
13
c2
14
16
15
17
13
15
11
15
09
12
CONCLUSION:
In present investigation we have carried out the synthesis of some 2-substituted derivatives of
quinazolinone by different substitutions like dimethylaminomethyl and diphenylaminomethyl, etc.
Since the present new three (a1, b1, c1) Quinazolinone derivatives could exhibit potent
Antimicrobial activity comparable with the standard employed, it is desirable to determine their
toxicity to decide on whether to go for further screening or not.
ACKNOWLEDGEMENT:
I am very much thank full to the management of Procadence Institute of Pharmaceutical sciences for
providing necessary facilities. I am also grateful to my colleagues and my friends for their kind help
from time to time at each and every step of this work.
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