KF/Al2O3 catalyzed one-pot three-component process for the synthesis of some 2-thioxoquinazolin-4(1h)-one derivatives

Article abstract of DOI:10.14233/ajchem.2013.14214

Three component one-pot reaction for synthesis of 2-thioxoquinazolin-4(1H)- ones are given by the condensation of isatoic anhydride, primary amine and phenyl isothiocyanate by using KF/Al2O3 as a environmentally friendly catalyst.

Full text of DOI:10.14233/ajchem.2013.14214

Asian Journal of Chemistry; Vol. 25, No. 11 (2013), 5975-5977
http://dx.doi.org/10.14233/ajchem.2013.14214
KF/Al2O3 Catalyzed One-Pot Three-Component Process for the
Synthesis of Some 2-Thioxoquinazolin-4(1H)-one Derivatives
*
FARHAD HATAMJAFARI, FARZAD ALIJANICHAKOLI and MOHAMMADJAVAD MOHAMMADMOHTASHAM
Department of Chemistry, Faculty of Science, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
*Corresponding author: E-mail: farzadalijanichakoli@yahoo.com
(Received: 19 June 2012;
Accepted: 22 April 2013)
AJC-13381
Three component one-pot reaction for synthesis of 2-thioxoquinazolin-4(1H)-ones are given by the condensation of isatoic anhydride,
primary amine and phenyl isothiocyanate by using KF/Al2O3 as a environmentally friendly catalyst.
Key Words: 2-Thioxoquinazolin-4(1H)-one, One-pot, Three component, KF/Al2O3, Microwave.
O
O
INTRODUCTION
R2
N
O
KF/Al2O3,
Ph NCS
Today multicomponent reactions (MCRs) emphasizes the
development of organic compounds as drug precursor on
environmentally friendly when synthesized compounds
without solvent and catalyst or water solvent and non-toxic
catalyst. Multicomponent reactions aid to play a key role in
the development of synthetic compounds because of their
possible generation of an adduct in a single step from multi
reactants usually used by bond-forming efficiency1. Applica-
tion of multicomponent reaction is on the high chemoselectivity
in the presence of all the reactants2.
+
R2
NH2
N
H
S
N
H
O
R1
R1
Scheme-I
IR spectral data of 3-benzyl-2,3-dihydro-2-thioxoquina-
zoline-4(1H)-one (4b) shows the characteristic single broad
N-H peak in the range 3280 cm-1, a sharp C=O peak at 1698
cm-1 and C=S peak at 1185 cm-1. 1H NMR shows characteristic
broad singlet for N-H at δ 12.01 in addition to those due to
aromatic protons at d 7.33-7.86 ppm13. In 13C NMR C=S appears
at δ 170 C=O appears at δ 161 ppm. Therefore in the present
investigation we have used KF/Al2O3 is a widely used solid
supported reagent which is cheap and easy for catalysis of a variety
of reactions. Due to its strongly basic nature it has been used as
a replacement for organic bases in a number of organic reactions18.
Variously substituted isothiocyanates were condensed isatoic
anhydride, primary amine and phenyl isothiocyanate in water
by using KF/Al2O3 as a environmentally friendly catalyst to
afford the desired 2-thioxoquinazolin-4(1H)-one derivatives in
60-79 % yields and was completed within 90-140 min (Table-1).
All chemicals were obtained from Merck or Fluka without
further purification. Melting points were determined on an
Electrothermal 9100 melting point apparatus and are uncor-
rected. IR spectra were measured on a Shimadzu IR-470
spectrophotometer. 1H and 13C NMR spectra were determined
on Bruker 500 DRXAVANCE instrument at 500 and 125 MHz,
respectively. The element analyses (C, H, N) were obtained
from a Carlo ERBA Model EA 1108 analyzer carried out on
Perkin-Elmer 240c analyzer.
Quinazolinones are very important structure in the field
of drug chemistry with wide range of biological and pharma-
cological activity3. The quinazolinones scaffold are important
class of fused heterocycles with a show promise such as anti-
inflammatory4, antimalarial5, anti HIV6 and anti cancer7 and
dihydrofolate reductase inhibitors8. Moreover, few methods
are reported for the synthesis of 2-thioxoquinazolin-4-ones,
as most of the methods reported are for quinazolin-2,4(1H,3H)-
diones9,10
.
Several methods have been proposed for quinazolinones
over the years, provide a simple method with the environ-
mentally friendly catalyst for synthesis of 2-thioxo-
quinazolinones. As part of our ongoing interest in
developing new methods for the synthesis of various
heterocyclic scaffolds11-17, therefore in this study, we have
synthesized derivatives of 2-thioxoquinazolin-4(1H)-one
with the condensation of isatoic anhydride, primary amine
and phenyl isothiocyanate by using KF/Al2O3 as a catalyst
(Scheme-I).

5976 Hatamjafari et al.
Asian J. Chem.
TABLE-1
SYNTHESIS OF VARIOUS 2-THIOXOQUINAZOLIN-4(1H)-ONES FROM DIFFERENT
ISATOIC ANHYDRIDE, PRIMARY AMINE AND ISOTHIOCYANATE
Entry
R1
R2–NH2
m.p. (ºC)
Yields (%)
Reaction time (min)
100
NH2
H
307-309
76
4a
NH2
H
meta-Cl
H
253-256
324-325
264-266
70
65
60
120
120
140
4b
4c
4d
NH2
Cl
H
317-319
76
90
4e
NH2
Typical synthesis of compounds (4a-e): A mixture of
KF/Al2O3 (0.2 g), isatoic anhydride (1 mmol), primary amine
(2 mmol) and phenyl isothiocyanate (1 mmol) was refluxed
in ethanol (5 mL) for 90-140 min. The progress of reaction
was monitored by TLC. The mixture was extracted with 3 cm
× 30 cm CH2Cl2, filtered and dried with anh. Na2SO4 sulphate.
The solution was dried under high vacuum and the resulting
solid residue recrystallized from ethanol to give the pure crysta-
lline solid (4a-e).
νmax, cm-1): 3291 (N-H), 3036 (C-Harom), 1677 (C=O), 1179
(C=S); 1H NMR (500 MHz, DMSO): δ = 1.79 (d, J = 7.1 Hz,
3H), 2.02 (q, J = 7.1 Hz, H), 7.15-7.82 (m, 9H , CHarom), 11.96
(s, 1H, NH); 13C NMR (125 MHz, DMSO): 27.7, 46.5, 58.2,
113.8, 114.5, 115.8, 118.6, 121.9, 125.6, 128.5, 132.4, 134.9,
138.0, 145.4, 147.3, 160.1, 171.9, ppm. MS (m/z, %): 282
(M+). Anal. calcd. (%) for C16H14N2OS: C, 68.06; H, 5.00; N,
9.92. Found (%): C, 67.81; H, 4.76; N, 9.71.
3-(4-Chlorobenzyl)-2,3-dihydro-2-thioxoquinazolin-
4(1H)-one (4e): White powder, m.p. 317-319 ºC; IR (KBr,
νmax, cm-1): 3122 (N-H), 3032 (C-Harom), 1681 (C=O), 1209
(C=S); 1H NMR (500 MHz, DMSO): δ = 5.16 (s, 2H), 7.16-
7.79 (m, 8H , CHarom), 12.02 (s, 1H, NH); 13C NMR (125 MHz,
DMSO): 46.4, 115.8, 122.4, 125.0, 126.7, 127.7, 130.6, 133.2,
134.5, 140.8, 145.8, 157.1, 172.3 ppm. MS (m/z, %): 302 (M+).
Anal. calcd. (%) for C15H11N2OSCl: C, 59.50; H, 3.66; N, 9.25.
Found (%): C, 59.33; H, 3.50; N, 9.18.
2,3-Dihydro-3-phenyl-2-thioxoquinazolin-4(1H)-one
(4a): White powder, m.p. 307-309 ºC; IR (KBr, νmax, cm-1):
1
3239 (N-H), 3091 (C-Harom), 1676 (C=O), 1189 (C=S); H
NMR (500 MHz, DMSO): δ = 7.29-7.96 (m, 9H , CHarom),
12.03 (s, 1H, NH); 13C NMR (125 MHz, DMSO): 118.6, 119.1,
121.3, 124.6, 125.0, 128.8, 129.9, 132.8, 137.1, 138.6, 158.8,
177.0 ppm. MS (m/z, %): 254 (M+). Anal. calcd. (%) for
C14H10N2OS: C, 66.12; H, 3.96; N, 11.02. Found (%): C, 65.71;
H, 3.81; N, 10.74.
Conclusion
3-Benzyl-2,3-dihydro-2-thioxoquinazolin-4(1H)-one
(4b): White powder, m.p. 253-256 ºC; IR (KBr, νmax, cm-1):
We have developed an efficient, one-pot synthesis of
2-thioxoquinazolin-4(1H)-ones by the condensation of isatoic
anhydride, primary amine and phenyl isothiocyanate by using
KF/Al2O3 in providing increased yields. KF/Al2O3 can act as
heterogeneous catalyst which is low cost and environmentally
friendly.
1
3280 (N-H), 3080 (C-Harom), 1698 (C=O), 1185 (C=S); H
NMR (500 MHz, DMSO): δ = 5.59 (s, 2H), 7.33-7.86 (m, 8H,
CHarom), 12.01 (s, 1H, NH); 13C NMR (125 MHz, DMSO):
44.8, 111.5, 114.4, 122.8, 125.1, 126.7, 127.8, 128.9, 134.1,
135.7, 138.1, 161.0, 170.0 ppm. MS (m/z, %): 268 (M+).Anal.
calcd. (%) for C15H12N2OS: C, 67.14; H, 4.51; N, 10.44. Found
(%): C, 66.89; H, 4.21; N, 10.26.
ACKNOWLEDGEMENTS
The authors gratefully acknowledged the financial support
from the Research Council of Tonekabon Branch IslamicAzad
University, Iran.
7-Chloro-2,3-dihydro-3-phenyl-2-thioxoquinazolin-
4(1H)-one (4c): White powder, m.p. 324-326 ºC; IR (KBr,
νmax, cm-1): 3188 (N-H), 3010 (C-Harom), 1700 (C=O), 1200
(C=S); 1H NMR (500 MHz, DMSO): δ = 7.30-7.92 (m, 8H,
CHarom), 12.06 (s, 1H, NH); 13C NMR (125 MHz, DMSO):
20.1, 55.5, 113.1, 115.2, 123.9, 124.2, 125.7, 126.5, 129.2,
131.9, 135.6, 138.8, 153.7, 169.3 ppm. MS (m/z, %): 288 (M+).
Anal. calcd. (%) for C14H9N2OSCl: C, 58.23; H, 3.14; N, 9.70.
Found (%): C, 57.95; H, 2.85; N, 9.58.
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KF/Al2O3 Catalyzed One-Pot Three-Component Synthesis of 2-Thioxoquinazolin-4(1H)-one Derivatives 5977
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