Synthesis of novel 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfinylmethyl)-3H- quinazolin-4-one

Article abstract of DOI:10.1080/10426507.2011.634466

Condensation of 2-mercapto-3H-quinazolin-4-one (1) with chloroacetic acid gave 4-oxo-3,4-dihydroquinazoline-2-yl-sulfanyl)-acetic acid (2) that with anthranilamide (3) gave 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H- quinazolin-4-one (4). Oxidation of 4 with sodium hypochlorite in alkaline medium gave the novel product, 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfinyl methyl)-3H-quinazolin-4-one) (5). The entire sequences of reactions in this work have been carried out using eco-friendly solvents and green conditions. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Full text of DOI:10.1080/10426507.2011.634466

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Synthesis of Novel 2-(4-
Oxo-3,4- Dihydroquinazolin-2-
Ylsulfinylmethyl)-3H-Quinazolin-4-One
B. Srinivasa Reddy a , A. Naidu a & P. K. Dubey a
a Department of Chemistry, Hyderabad College of Engineering ,
Jawaharlal Nehru Technological University, Kukatpally , Hyderabad ,
Andhra Pradesh , India
Published online: 27 Mar 2012.
To cite this article: B. Srinivasa Reddy , A. Naidu & P. K. Dubey (2012) Synthesis of Novel 2-(4-
Oxo-3,4- Dihydroquinazolin-2-Ylsulfinylmethyl)-3H-Quinazolin-4-One, Phosphorus, Sulfur, and Silicon
and the Related Elements, 187:5, 598-605, DOI: 10.1080/10426507.2011.634466
To link to this article: http://dx.doi.org/10.1080/10426507.2011.634466
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Phosphorus, Sulfur, and Silicon, 187:598–605, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.634466
SYNTHESIS OF NOVEL 2-(4-OXO-3,4-
DIHYDROQUINAZOLIN-2-YLSULFINYLMETHYL)-3H-
QUINAZOLIN-4-ONE
B. Srinivasa Reddy, A. Naidu, and P. K. Dubey
Department of Chemistry, Hyderabad College of Engineering, Jawaharlal Nehru
Technological University, Kukatpally, Hyderabad, Andhra Pradesh, India
GRAPHICAL ABSTRACT
O
N
O
N
O
HN
NH
NH
SH
C
S
N
H2
O
(1)
(5)
Abstract Condensation of 2-mercapto-3H-quinazolin-4-one (1) with chloroacetic acid gave
4-oxo-3,4-dihydroquinazoline-2-yl-sulfanyl)-acetic acid (2) that with anthranilamide (3)
gave 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-quinazolin-4-one (4). Oxidation
of 4 with sodium hypochlorite in alkaline medium gave the novel product, 2-(4-oxo-3,4-
dihydroquinazolin-2-ylsulfinyl methyl)-3H-quinazolin-4-one) (5). The entire sequences of
reactions in this work have been carried out using eco-friendly solvents and green conditions.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Anthranilamide; 2-Thioquinazolinone; 2-Chloromethyl-3H-quinazolin-4-one;
chloroacetic acid; triethylamine
INTRODUCTION
The quinazolinone ring system forms an important class of N-heterocyclic com-
pounds as it is present in a large number of compounds with useful biological properties
Received 30 August 2011; accepted 19 October 2011.
The authors are indebted to the University Grants Commission, Govt. of India, New Delhi, for financial
support. They are also thankful to the authorities of Jawaharlal Nehru Technological University, Hyderabad, for
providing laboratory facilities.
Address correspondence to B. Srinivasa Reddy, Department of Chemistry, Hyderabad College of Engineer-
ing, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad, Andhra Pradesh 500085, India. E-mail:
srinivasjntu123@gmail.com
598

SYNTHESISOFNOVEL2-(4-OXO-3, 4-DIHYDROQUINAZOLIN-2-YLSULFINYLMETHYL)-3H-QUINAZOLIN-4-I5B9E9
such as anti-inflammatory,1,2 anticonvulsant,3 hypotensive,4 and antimalarial5 types. 2-
Thioquinazolinones possess good analgesic activities.6, 7 2-Heterylquinazolin-4(3H)-ones
exhibit a wide range of pharmacological properties,8 such as good antimicrobial activity
against different species of gram-positive bacteria,9 gram-negative bacteria,10 pathogenic
fungi.11,12 In view of this wide range of pharmacological activities, the quinazolinone
derivatives have been the target of a large number of organic synthetic efforts.13–16
2-Mercapto-3H-quinazolin-4-one (1) has been prepared earlier from anthranilamide
(3) by reacting with potassium ethylxanthate under refluxing conditions.17 Reaction of
1 with substitutedphenacyl bromide is reported18 to yield 2-(2–4-substitutedphenyl)-2-
oxo-ethylthio)-3-substituted-quinazolin-4(3H)-ones. Literature studies indicate different
methods19 for the preparation of 4-oxo-3, 4-dihydroquinazoline-2-yl-sulfanyl)-acetic acid
(2). N-Chloroacetylanthranilic acid ethyl ester is reported20 to react with potassium thio-
cyanate giving 2. Synthesis of 2-chloromethyl-3H-quinazolin-4-one (8) involves conden-
sation of 2-aminobenzonitrile with chloroacetyl chloride followed by cyclization. The
reaction of 1 with 2-(1-chloroethyl)-1H-benzimidazole resulting in the formation of 2-
[1-(1H-benzoimidazol-2-yl)-ethylsulfanyl]-3H-quinazolin-4-one was reported earlier from
these labs.21
In view of the information given above, it was considered worthwhile to study the
reaction of 1 with heterocyclic methyl halides and subsequent chemical modifications of
the condensation products as new chemical entities with potential biological activities.
RESULTS AND DISCUSSION
Compound 1 on reaction with chloroacetic acid in water containing K2CO3 as a
mild base under reflux for 1–2 h gave 2. The latter on condensation with 3 under reflux
in aqueous HCl for 5 h gave a product, which has been characterized as 2-(4-oxo-3,4-
dihydroquinazolin-2-ylsulfanylmethyl)-3H-quinazolin-4-one (4). The structure of 4 was
established on the basis of its spectral and analytical data. Thus, its IR (KBr) showed a
very broad band in the region 3200–3100 cm−1 assignable to the two NH stretching
vibrations and a very strong, sharp peak at 1660 cm−1 assignable to the two amide carbonyl
groups put together. Its 1H NMR (DMSO-d6) showed signals at δ 4.50 (s, 2H, CH2 ),
7.40–8.00 (m, 8H, aryl protons), and 12.70 (br s, 2H, D2O exchangeable, 2 × NH ).
Its LCMS spectrum showed the molecular ion peak [M+ + 1] at m/z 337 corresponding
to a molecular mass of 336 when recorded in the Q + 1 mode. Compound 1 required in
the present work was itself prepared from anthranilamide (3) by reacting with potassium
ethylxanthate under refluxing conditions in aqueous ethanol for 20 h in almost quantitative
yield using an earlier procedure17 (Scheme 1).
Oxidation of 4 with sodium hypochlorite in alkaline medium gave the product 2-(4-
oxo-3,4-dihydroquinazolin-2-ylsulfinylmethyl)-3H-quinazolin-4-one) (5). The structure of
5 was established on the basis of its spectral and analytical data. Thus, its IR (KBr) showed
a very broad band in the region 3200–3100 cm−1 assignable to the two NH stretching
vibrations, a very strong, sharp peak at 1660 cm−1 assignable to the two amide carbonyl
groups put together, and a very sharp band at 1200–1150 cm−1 assignable to S O stretching.
Its 1H NMR (DMSO-d6) showed signals at δ 4.55 (AB quartet, J = 7.2 Hz, 2H, CH2 ),
7.40–8.00 (m, 8H, aryl protons), and 12.70 (broad s, 2H, D2O exchangeable, 2 × NH ).
The appearance of –CH2 protons as an AB quartet is a characteristic feature of molecules
having an adjacent sulfoxide grouping due to the nonequivalence and diastereotopic nature

600
B. S. REDDY ET AL.
O
N
NH
SH
+
Cl CH2 COOH
(1)
aq. K2CO3/∆ / 1--2 h.
O
NH
H2
S C COOH
N
(2)
3 / 4N HCl /
∆/ 4-- 5 h.
O
N
O
N
O
N
O
N
HN
NH
HN
NH
˚
NaOCl/0--5 C/2--3 h.
C
S
C
S
H2
H2
O
(5)
(4)
3/EtOH/∆/ 2-- 3 h.
AcOH/ 3--4 h./
1/aq. K2CO3/ RT/ 2--3 h.
∆
O
S
NH
S C O C2H5
O
C
N
O
NH2
H2
(9)
NH
H
N
N
S
O
N
S
O
K
EtO C S
(7)
HN
EtOH/ RT/ 3--4 h.
Cl
C
(8)
H2
AcOH / 3-- 4 h. /
∆
O
O
NH2
NH2
O
chloroacetylchloride
PEG-600/r.t./1--2 h.
NH2
(3)
NH
C
CH2 Cl
1/aq. K2CO3/ r.t./ 2--3 h.
(6)
Scheme 1
of the methylene protons. The 13C-NMR spectrum (DMSO-d6/TMS) of 5 showed signals
at δ 30.80, 33.40, 35.80, 120.60, 121.10, 124.10, 124.80, 125.80, 126.10, 126.50, 126.80,
133.00, 134.40, 148.50, 161.40, 162.30. The LCMS spectrum of 5 showed the molecular ion
peak [M+·+ 1] at m/z 353 corresponding to a molecular mass of 352 when recorded in the Q
+ 1 mode. It may be mentioned here that the conversion of 4 to 5 using sodium hypochlorite
in aqueous solution in the presence of aqueous alkali at 0 ◦C–5 ◦C for 2–3 h is a significant
achievement of this synthetic sequence that involves selective transformation of a thioether
(i.e., 4) to an S-oxide (i.e., 5) under very mild and green conditions. The side product of this
oxidation, i.e., sodium chloride, does not pose any effluent problem and is removed very

SYNTHESISOFNOVEL2-(4-OXO-3, 4-DIHYDROQUINAZOLIN-2-YLSULFINYLMETHYL)-3H-QUINAZOLIN-4-I6B0E1
easily due to its water solubility. Furthermore, the conversion of thioether (such as 4) to its
S-oxide (such as 5) using other oxidizing agents like m-CPBA in chloroform or using H2O2
in acetic acid is sometimes beset with problems22 such as overoxidation or underoxidation
or formation of side products due to N-oxidation. Removal of these impurities from the
product is usually very difficult and the problem is commonly found in the preparation of
several drugs in the antiulcer segment like Omeprazole, Pantoprazole, and Rabeprazole.
In another approach, 4 could also be synthesized from 2-[2-(4-oxo-3,4-
dihydroquinazolin-2-ylsulfanyl)acetylamino]benzamide (7) by simple refluxing in
glacial acetic acid. Compound 7 itself was synthesized from 3 by reaction with
chloroacetyl chloride in polyethylene glycol (PEG) at RT for 1–2 h yielding 2-(2-
chloroacetylamino)benzamide (6), which on treatment with 1 in aqueous K2CO3 gave 7.
The structure of 7 was assigned on the basis of its spectral and analytical data. Thus, its
IR (KBr) showed a very broad band of medium intensity in the region 3200–3100 cm−1
assignable to the one NH stretching vibrations and NH2 put together; a strong, sharp
band at 1700 cm−1 assignable to the two carbonyl groups; and a very strong, sharp peak
1
at 1670 cm−1 assignable to the amide carbonyl group. Its H NMR (DMSO-d6) showed
signals at δ 4.44 (s, 2H, CH2-), 7.36–8.00 (m, 8H, aryl protons), 8.09 (broad s, 2H, D2O
exchangeable, NH2), and 12.44–12.70 (broad two singlets, 2H, D2O exchangeable, 2 ×
NH). Its LCMS spectrum showed the molecular ion peak [M+·+ 1] at 355 corresponding
to a molecular mass of 354 when recorded in the Q + 1 mode. The structure of the
intermediate 6 was also assigned based on its melting point and spectral data reported
earlier in literature.23
In another approach, reaction of 8 with 1 in water as a solvent containing K2CO3
at r.t. for 2–3 h gave 4, identical in mp, mmp, and TLC with that of the same product
obtained in the routes described above, (i.e., 2 + 3 → 4 and 3 → 6 → 7 → 4). The
former compound, i.e., 8, in turn, was synthesized from 6 on cyclization in acetic acid
under refluxing conditions.
In another approach, 4 could be prepared by the condensation of (4-oxo-3, 4-
dihydroquinazolin-2-ylmethyl)dithiocarbonic acid ethyl ester (9) with 3 in refluxing
ethanol. 9, in turn, was synthesized by the reaction of 8 with potassium o-ethyl dithio-
carbonate in ethanol at r.t. for 1–2 h in 60% yield. Potassium o-ethyl dithiocarbonate was
prepared from CS2, KOH, and ethanol. The structure of 9 was established on the basis of
its spectral and analytical data. Thus, its IR (KBr) showed a very broad band in the region
3200–3100 cm−1 assignable to NH stretching vibration, a very strong, sharp peak at
1660 cm−1 assignable to the amide carbonyl group, and a very broad band in the region
1200–1150 cm−1 assignable to C S stretching vibration. Its 1H NMR (DMSO-d6) showed
signals at δ 1.20 (t, J = 7.02 Hz, 3H, CH2 CH3), 4.40 (q, J = 7.02 Hz, 2H, CH2 CH3),
4.50 (s, 2H, CH2 ), 7.20–8.50 (complex m, 4H, aryl protons), 12.58 (broad s, 1H, D2O
exchangeable proton NH ). Its LCMS spectrum showed the molecular ion peak [M+ +
1] at m/z 281 corresponding to a molecular mass of 280 when recorded in the Q + 1
mode.
A plausible mechanism for the transformation of 9 to 4 by condensation of 9 with
3 is shown in Scheme 2. The reaction, initially, involves the nucleophilic attack by the
amino group of 3 on the xanthate carbon of 9 yielding the intermediate 9A that loses
elements of ethanol to form 9B. The latter, then, undergoes ring closure involving a second
but intramoleular, nucleophilic attack by the amide amino group on the xanthate carbon to
form 9C, which changes to 9D. This intermediate then undergoes loss of elements of H2S
in a bid to aromatize to form the final product 4.

602
B. S. REDDY ET AL.
O
N
O
O
O
N
NH
CH2
S
C
H2N
OC2H5
NH
CH2
(9A)
H2N
S
H2N
(3)
S
N
S
C
H2
(9)
OC2H5
O
O
O
H
N
O
NH
H2N
C2H5OH
H
NH
CH2
N
N
H
S
C
CH2
(9B)
N
N
S
S
S
H
(9C)
O
N
O
O
O
HN
-H2S
NH
NH
HN
S
CH2
(4)
N
N
N
H
S
CH2
(9D)
HS
Scheme 2
All the reactions described in this paper are depicted in Scheme S1.
CONCLUSION
The target molecule 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-
quinazolin-4-one (4) has been synthesized by four different routes. Of all the methodologies
discussed, the condensation of 8 with 1 in water as solvent using K2CO3 as base appears
to be the better and efficient route for the product obtained, compared to the other three
routes. Oxidation of 4 to 5 is a green process leaving behind NaCl as the byproduct, which
is environmentally harmless. The entire sequence of reactions shown in Scheme S1 have
been carried out using eco-friendly solvents and green conditions.
EXPERIMENTAL SECTION
General Conditions
Melting points are uncorrected and were determined in open capillary tubes in sulfuric
acid bath. TLC was performed on plastic sheets coated with silica gel-G (supplied by
Merck and Co) and spotting was done using iodine or UV-light. IR spectra were recorded
1
with Perkin-Elmer 1000 instrument in KBr phase, H-NMR and 13C-NMR on VARIAN
instrument operating at 400 MHz and 100 MHz, respectively, and Mass spectra on Agilent-
LC-MS instrument giving only M+· Values using Q + 1 or Q – 1 mode. Anthranilamide
(3) was obtained from commercial suppliers and used as such without further purification.
Preparation of (4-oxo-3,4-dihydroquinazolin-2-ylsulfanyl)-acetic Acid (2)
from 1. A mixture of 1 (1.78 g, 0.01 mol), chloroacetic acid (3.55 g, 0.01 mol), K2CO3
(1.92 g, 0.01 mole), and water (10 mL) was refluxed for 1 h. After completion of reaction
(as indicated by TLC using hexane:ethyl acetate, 7:3 as eluent), the mixture was cooled
to r.t. and treated with acetic acid (1 mL) until neutral. The separated solid was filtered,

SYNTHESISOFNOVEL2-(4-OXO-3, 4-DIHYDROQUINAZOLIN-2-YLSULFINYLMETHYL)-3H-QUINAZOLIN-4-I6B0E3
washed with water (2 × 40 mL), and dried to obtain crude 2. Pure 2 was obtained by
recrystallization from ethanol.
◦
◦
2: Colorless solid; Yield = 1.90 g (80%); mp = 178 C–80 C; (Ref. 19 mp =
180 ◦C–82 ◦C); IR (KBr): 3200–3000 cm−1 (very broad, two NH ), 1700–1665 cm−1
(s, sharp, C O of the amide carbonyl group). 1H-NMR (DMSO-d6/TMS): δ 4.00 (s, 2H,
CH2 ), 7.30–8.00 (complex m, 4H, aryl protons), 12.75 (br s, 2H, D2O exchangeable,
NH and COOH). LCMS, m/z = 237 (M+· + 1).
Preparation of 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-
quinazolin-4-one (4) from 2 and 3. A mixture of 2 (1.18 g, 0.05 mol), 3 (0.68 g, 0.05
mol), and aqueous HCl (4N, 50 mL) was refluxed for 5–6 h. On completion of reaction (as
indicated by TLC using chloroform:methanol, 7:3 as eluent), the mixture was cooled to r.t.,
neutralized with aqueous ammonia (5 mL) until neutral. The separated solid was filtered,
washed with water (2 × 50 mL), and dried to obtain crude 4. The latter on recrystallization
from ethanol gave pure 4.
◦
◦
4: Colorless solid; Yield = 1.16 g (56%); mp = 255 C–58 C; IR (KBr): 3200–
3000 cm−1 (very broad, 2 × NH ) 1700–1665 cm−1 (strong, sharp, two carbonyls of
1
the two amide groups); H-NMR (DMSO-d6/TMS): δ 4.50 (s, 2H, CH2 ), 7.40–8.00
(complex, m, 8H, aryl protons), 12.70 (br s, 2H, D2O exchangeable, 2 × NH ). LCMS,
m/z = 337 (M+· + 1). Element. Anal: Found C = 61.00%, H = 3.80%, N = 17.00;
C17H12N4O2S requires C = 60.70%, H = 3.60%, N = 16.66%.
Preparation of 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-
quinazolin-4-one (4) from 1 and 8 using K2CO3 and water. A mixture of 1 (1.78
g, 0.01 mol), 8 (2.32, 0.012 mol), K2CO3 (1.92 g, 0.015 mol), and water (50 mL) was
stirred at r.t. for 2–3 h. After completion of the reaction (as indicated by TLC using chlo-
roform:methanol, 5:5 as eluent), the reaction mixture was treated with acetic acid (1 mL)
until neutral. The separated product was filtered, washed with water (2 × 25 mL), and
◦
◦
dried. Yield = 3.02 g (90%). Pure 4 (EtOH), mp = 255 C–58 C, identical in mp,
mmp, and TLC with that of the same product obtained in the route described above, i.e.,
2 + 3 → 4.
Preparation of 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-
quinazolin-4-one (4) from 3 and 9. A mixture of 3 (0.68 g, 0.05 mol), 9 (1.40 g, 0.05
mol), and ethanol (50 mL) was refluxed on a hot water bath for 4–5 h. After completion
of the reaction (as indicated by TLC using chloroform:methanol, 7:3 as eluent), the
mixture was poured into ice-cold water. The separated product was filtered, washed with
water (2 × 50 mL), and dried. Yield = 2.08 g (50%). Pure 4 (EtOH), identical in mp,
mmp, and TLC with that of the same product obtained in the route described above, i.e.,
2 + 3 → 4.
Preparation of 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-
quinazolin-4-one (4) from 7. To a suspension of 7 (2.12 g, 0.01 mol) in AcOH (30 mL),
the mixture was heated on a water bath for 3 h. After cooling, the separated product was
filtered, washed with acetic acid (2 × 20 mL), and dried. Pure 4 (EtOH), identical in mp,
mmp, and TLC with that of the same product obtained in the route described above, i.e.,
2 + 3 → 4.
Preparation of 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfinyl methyl)-3H-
quinazolin-4-one) (5) from 4. To a solution of NaOH (0.1 g) in water (10 mL),
acetonitrile (10 mL) was added compound 4 (1.76 g, 0.05 mol) at r.t. The mixture was
◦
cooled to 0 C and sodium hypochlorite (11 mL, 0.06 mol, assay 4%) was added at
0 ◦C–5 ◦C over 10 min and the reaction mixture was stirred at 0 ◦C–5 ◦C for 40 min. On

604
B. S. REDDY ET AL.
completion of reaction (as indicated by TLC using hexane:ethyl acetate, 5:5 as eluent), the
mixture was quenched with a solution of sodium thiosulfate (3.0 g) in water (50 mL). The
◦
◦
resulting mixture was then cooled to 0 C–5 C and the pH adjusted to ≥7.0 with acetic
acid (1 mL). The mixture was kept aside stirring at r.t. for 1 h. The separated solid was
filtered, washed with water (2 × 50 mL), and dried to obtain crude 5. Pure 5 was obtained
by recrystallization from ethyl acetate.
◦
5: Colorless solid; Yield = 1.62 g (80%); mp = 170 C–73 ◦◦C; IR (KBr): 3200–
3000 cm−1 (very broad, two NH ), 1700–1665 cm−1 (strong, sharp, two carbonyls
1
of the two amide groups), 1180 cm−1 assignable to S O stretching; H-NMR (DMSO-
d6/TMS): δ 4.55 (AB, J = 7.2 Hz, quartet, 2H, CH2 ), 7.40–8.00 (complex, m, 8H,
aryl protons), 12.70 (broad s, 2H, D2O exchangeable, 2 × NH ). 13C-NMR (DMSO-
d6/TMS): δ 30.80, 33.40, 35.80, 120.60, 121.10, 124.10, 124.80, 125.80, 126.10, 126.50,
126.80, 133.00, 134.40, 148.50, 161.40, 162.30. LCMS, m/z = 353 (M+· +1). Element.
Anal: Found C = 58.15%, H = 3.75%, N = 16.00%; C17H12N4O3S requires C = 58.00%,
H = 3.43%, N = 15.90%.
Preparation of 2-[2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanyl)-acety
lamino]-benzamide (7) form 6. A mixture of 1 (1.78 g, 0.01 mol), 6 (2.54, 0.012
mol), K2CO3 (1.92 g, 0.015 mol), and water (50 mL) was stirred at r.t. for 2–3 h. After
completion of the reaction, as monitored by TLC, (hexane:ethyl acetate, 6:4 as eluent),
the mixture was treated with acetic acid (1 mL) until neutral. The separated product was
filtered, washed with water (2 × 25 mL), and dried to obtain crude 7. Pure 7 was obtained
by recrystallization from hot EtOH.
7: Yellow solid; Yield = 3.00 g (85%); mp = 155 ◦C–57 ◦C; IR (KBr): 3200–3000
cm−1 (very broad, two NH stretching vibrations), 1700–1665 cm−1 (strong, sharp, two
1
carbonyls of two amide groups), H-NMR (DMSO-d6/TMS): δ 4.44 (s, 2H, CH2 ),
7.36–8.09 (complex, m, 8H, aryl protons), 8.10 (broad s, 2H, D2O exchangeable, NH2),
12.40 (2 bs, 2H, D2O exchangeable, 2 × NH ). LCMS: m/z = 355 (M+· + 1). Element.
Anal: Found C = 57.80%, H = 4.20%, N = 16.10%; C17H14N4O3S requires C = 57.62%,
H = 3.98%, N = 15.81%.
Preparation of 2-chloromethyl-3H-quinazolin-4-one (8) from 6. A mixture
of 6 (2.12 g, 0.01 mol) and AcOH (30 mL) was heated on a water bath for 3 h. The mixture
was then cooled to r.t. The separated product was filtered, washed with acetic acid (2 ×
20 mL), and dried to obtain crude 8. Recrystallization from hot isopropanol gave pure 8.
◦
◦
8: Colorless solid; Yield = 1.55 g (80%); mp = 247 C–49 C; (Lit.20 mp =
249 ◦C–253 ◦C). IR (KBr): 3200–3000 cm−1 (very br, NH ), 1700–1665 cm−1 (strong,
sharp, two carbonyls of amide groups), 1H-NMR (DMSO-d6/TMS) δ 4.50 (s, 2H, CH2 ),
7.50–8.20 (complex, m, 4H, aryl protons), 12.50 (br s, 1H, D2O exchangeable proton,
NH ). LCMS: m/z = 195 (M+· +1).
Preparation of (4-oxo-3,4-dihydroquinazolin-2-ylmethyl)dithiocarbonic
Acid ethyl Ester (9) from 8. A mixture of 8 (1.94 g, 0.01), potassium ethoxydithiocar-
bamate (1.60 g, 0.01 mol), and ethanol (30 mL) was refluxed for 3–4 h. Then, the reaction
mixture was cooled to r.t. and the separated KBr salt was filtered and washed with ethanol
(20 mL). The ethanolic filtrate was distilled off and the residue diluted with water (20 mL).
The separated solid was filtered, washed with water (20 mL), and dried to obtain crude 9.
The latter was recrystallized from hot isopropanol to obtain ◦pure 9.
◦
9: Yellow solid; Yield = 1.68 g (60%); mp = 157 C–159 C; IR (KBr): 3200–
3100 cm−1 (very br, NH ), 1660 cm−1 (strong, sharp, C O of the amide group), 1180
1
cm−1 (br, C S of the xanthate group). H-NMR (DMSO-d6/TMS): δ 1.20 (t, J = 7.02

SYNTHESISOFNOVEL2-(4-OXO-3, 4-DIHYDROQUINAZOLIN-2-YLSULFINYLMETHYL)-3H-QUINAZOLIN-4-I6B0E5
Hz, 3H, CH2 CH3), 4.40 (s, J = 7.02 Hz, 2H, CH2 CH3), 4.50 (s, 2H, CH2 ),
7.20–8.50 (complex, m, 4H, aryl protons), 12.58 (br s, 1H, D2O exchangeable proton,
NH). LCMS: m/z = 281 (M+· +1). Element. Anal: Found C = 51.70%, H = 4.50%, N =
10.20%; C12H12N2O2S2 requires C = 51.41%, H = 4.31%, N = 9.99%.
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