Synthesis of substituted 2-benzoylaminothiobenzamides and their ring closure to substituted 2-phenylquinazoline-4-thiones

Article abstract of DOI:10.3390/60400323

Acylation of 2-aminothiobenzamide or 2-methylaminothiobenzamide with substituted benzoyl chlorides has been used to synthesise the corresponding 2-benzoyl-aminothiobenzamides whose subsequent sodium methoxide-catalysed ring closure gives the corresponding quinazoline-4-thiones. These compounds were characterised by means of their ¹H- and ¹³C-NMR spectra. The preferred tautomeric form of selected compounds has been discussed on the basis of their ¹³C-NMR, IR and Raman spectra. It has been found that in the given medium 1-methyl-quinazoline-4-thiones undergo a replacement of the sulphur substituent by oxygen giving 1-methyl-quinazoline-4-ones. In strong acid media, 2-benzoylaminothiobenzamide is cyclised through its sulphur atom to give 2-phenylbenzo[d-1,3]thiazin-4-one.

Full text of DOI:10.3390/60400323

Molecules 2001, 6, 323-337
molecules
ISSN 1420-3049
http://www.mdpi.org
Synthesis of Substituted 2-Benzoylaminothiobenzamides and
Their Ring Closure to Substituted 2-Phenylquinazoline-4-
thiones
Jiří Hanusek1, Ludmila Hejtmánková2, Lenka Kubicová3 and Miloš Sedlák1,*
1
Department of Organic Chemistry, University of Pardubice, Čs. legií 565, 532 10 Pardubice, Czech
Republic, Tel. +420 40 603 7015, Fax +420 40 603 7068, e-mail: Jiri.Hanusek@upce.cz.
Research Institute of Pharmacy and Biochemistry, Kouřimská 17, 130 60 Prague 3, Czech
2
Republic, Tel. +420 40 603 8011, Fax +420 40 603 7068, e-mail: jjirman@serverpce.czcom.cz
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, 500 05
3
Hradec Králové, Czech Republic, Tel. +420 49 5067339, Fax. +420 49 5210002, e-mail:
kubicova@faf.cuni.cz
* Author to whom correspondence should be addressed; e-mail: Milos.Sedlak@upce.cz.
Received: 4 December 2000; in revised form 6 March 2001 / Accepted: 23 March 2001 / Published:
31 March 2001
Abstract: Acylation of 2-aminothiobenzamide or 2-methylaminothiobenzamide with
substituted benzoyl chlorides has been used to synthesise the corresponding 2-benzoyl-
aminothiobenzamides whose subsequent sodium methoxide-catalysed ring closure gives
the corresponding quinazoline-4-thiones. These compounds were characterised by means
of their 1H- and 13C-NMR spectra. The preferred tautomeric form of selected compounds
has been discussed on the basis of their 13C-NMR, IR and Raman spectra. It has been
found that in the given medium 1-methyl-quinazoline-4-thiones undergo a replacement of
the sulphur substituent by oxygen giving 1-methyl-quinazoline-4-ones. In strong acid
media, 2-benzoylaminothiobenzamide is cyclised through its sulphur atom to give 2-
phenylbenzo[d-1,3]thiazin-4-one.
Keywords: 2-Benzoylaminothiobenzamides, quinazoline-4-thiones, tautomerism, ring
closure.
Introduction

Molecules 2001, 6
324
Quinazoline-4-ones and their derivatives are well known for their pharmacological activity [1].
However, their synthesis mostly starts from anthranilic acid derivatives, in particular their N-acyl-
amides [2,3]. The aim of the present work is to synthesise the sulphur analogues of N-
benzoylaminoanthranilamides and to carry out their ring closure to the corresponding 2-phenyl-
quinazoline-4-thiones, which could show biological activity too.
Results and Discussion
Quinazoline-4-thiones can be synthesised by several ways: e.g. it is possible to transform the
corresponding oxygen derivative into its sulphur analogue by treating it with phosphorus
pentasulphide [4] or Lawesson’s reagent [5]. It is also possible to make use of the reactivity of
suitably substituted isothiocyanates [6]. In our work we have chosen the way of constructing the
heterocyclic skeleton which consists in the acylation of 2-aminothiobenzamide or 2-methylamino-
thiobenzamide with substituted benzoyl chlorides and subsequent ring closure of the thus obtained 2-
benzoylaminothiobenzamides (1a-m) in basic medium to give the quinazoline-4-thiones (2a-m)
(Scheme 1).
S
COCl
S
C
C
NH2
R1
NH2
Acetone
R2
+
(C2H5)3N
R2
NH
N C
R1
O
S
1a - 1m
N
CH3ONa
R1 = H, CH3
R2 = 4-OCH3, 4-CH3, 4-H, 4-Cl,
3-Br, 3-NO2, 4-NO2
N
R2
R1
2a - 2m
Scheme 1 - Preparation of 2-benzoylaminothiobenzamides and 2-phenylquinazoline-4-thiones
The starting 2-aminothiobenzamide and 2-methylaminothiobenzamide were prepared by two-step
syntheses from 2-aminobenzamide and 2-methylaminobenzamide, respectively. In the first step we
prepared the corresponding pyridinium salt by treatment with phosphorus pentasulphide [7], and in
the second step the pyridinium salt was transformed into the respective thioamide by our original
hydrolysis method in a toluene-water system. The benzoylation of the thioamides thus obtained was
carried out by treatment with commercial benzoyl chlorides in acetone solvent. The reaction gives 2-
benzoylaminothiobenzamides 1a-m, which are very sensitive to both basic and acidic media as well
as to air oxygen and heating (the melting temperature intervals are relatively broad, which is a
consequence of the decomposition during m. p. determination). Due to its low stability it was

Molecules 2001, 6
325
impossible to prepare compound 1e (R2 = 4-NO2) with sufficient purity for characterisation. In the
1
syntheses any contact with metals must be avoided, otherwise the H-NMR spectra show broadened
signals due to the presence of paramagnetic substances – most probably metal complexes of the
thioamides. The ring closure of 2-benzoylaminothiobenzamides 1a-m to the corresponding 2-(subst.
phenyl)quinazoline-4-thiones 2a-m is easily achieved in solutions of sodium methoxide even at room
temperature (Scheme 1).
The newly synthesised 2-(subst.phenyl)quinazoline-4-thiones 2a-f can exist in three tautomeric
forms (Scheme 2) similar to those of the parent compound, the unsubstituted quinazoline-4-thione
itself, whose structure was discussed previously, but only on the basis of its UV [8] and IR spectra
[9]. Therefore, we have focused our attention on interpretation of 13C-NMR, IR, Raman and UV
spectra. The IR spectra of the substances mentioned exhibit a broad band in the interval of 3150 –
3300 cm–1, which indicates the presence of NH group (valence vibrations). This finding together with
the fact that the Raman spectrum does not show any band in the region of 2500 – 2600 cm–1 (the
valence vibration of SH group) exclude structure III. Also the chemical shift of C4 in the region of
187.9 – 188.2 ppm is much higher than that of 2-aryl-4-allylthioquinazolines (157.8 – 158.6 ppm)
[10]. The differentiation between structures I and II is possible on the basis of comparison of the UV
spectra, or better still, that of the 13C-NMR shifts of C=S group. The absorption maximum of
derivatives 2a-f is at 360 nm, while that of the derivatives 2g-m (whose methyl group prefers a
tautomeric arrangement close to structure II) is at 388 nm. A similar conclusion follows from the 13C-
NMR shifts of C=S group: those of derivatives 2a-f lie in the region of 187.9 – 188.2 ppm, that of 2-
phenyl-3-methylquinazoline-4-thione is at 189.2 ppm, and those of derivatives 2g-m lie in the region
of 198.7 – 199.0 ppm. The shifts mentioned indicate that the preferred tautomeric form is I as it is the
case with the analogous 2-phenylquinazolin-4-ones too.
S
S
SH
NH
N
N
N
NH
N
R2
R2
R2
I.
II.
III.
Scheme 2 - Possible tautomeric structures of 2-(subst.phenyl)quinazoline-4-thiones
When synthesising the N-methyl derivatives 2g-m we observed that the cyclisation is followed by
desulphuration giving the corresponding 2-phenylquinazolin-4-one derivatives. This finding was
verified on preparative scale: we refluxed 1-methyl-2-(4-chlorophenyl)quinazoline-4-thione (2j) in
sodium methoxide and obtained 1-methyl-2-(4-chlorophenyl)quinazolin-4-one in 67% yield (Scheme
3). Similar desulphurations of quinazoline-4-thiones to quinazolin-4-ones were described earlier but
the reaction conditions were substantially different: either a preliminary S-alkylation [11-13] or
treatment with hydrogen peroxide [13].

Molecules 2001, 6
326
S
O
N
N
N
CH3ONa
R2
N
CH3
CH3
R2
R2= CH3O, CH3, H, Cl, NO2
Scheme 3 - Desulphuration of 1-methyl-2-(subst.phenyl)quinazoline-4-thiones
Moreover, we have found that in strong acid medium 2-benzoylaminothiobenzamide (1a)
undergoes ring closure through its sulphur atom, and the same reaction can also be presumed with the
other derivatives (1b-f). A similar reaction was described earlier with thioureide esters [14] and
selenoureide esters [15]. This finding can be interpreted by the SH group being a stronger nucleophile
in acid medium than the protonated nitrogen of thioamide group, the opposite being true in basic
media. When compound 1a was stirred in concentrated sulphuric acid at room temperature for three
days, the products isolated from the resulting reaction mixture involved (besides the unreacted
starting substance 1a) two cyclisation products: 2-phenyl-4-iminobenzo[d-1,3]thiazine and 2-
phenylbenzo[d-1,3]thiazin-4-one, the latter being formed by subsequent hydrolysis during isolation
(Scheme 4).
S
C
NH
N
O
N
NH2
S
S
H3PO4
H2O
(H2SO4)
NH C
O
Scheme 4 - Cyclisation of 2-benzoylaminothiobenzamide (1a) in acid medium
After prolonging the reaction time (to 7 days) and increasing of reaction temperature (60 °C) the
reaction products again included the starting material 1a, and a new product also appeared: bis(2-
phenylquinazolin-4-yl)sulphide formed by a parallel reaction. In order to suppress the oxidation, the
ring closure was carried out in anhydrous phosphoric acid at room temperature (14 days), which was
followed by hydrolysis in 50% aqueous methanol (30 min reflux). The HPLC-MS analysis of the
product showed that it contained 15% starting thioamide 1a and 85% 2-phenylbenzo[d-1,3]thiazin-4-

Molecules 2001, 6
327
one; the latter compound was then obtained in pure state by recrystallisation from aqueous methanol
(yield 49%).
The structure of the 2-benzoylaminothiobenzamides (1a-m) and cyclisation products (2a-m) was
verified by spectral methods (1H- and 13C-NMR, IR) and elemental analysis.
Conclusions
The 2-benzoylaminothiobenzamides and 1-methyl-2-phenyl-1H-quinazolin-4-thiones prepared by
new methods have not been described yet. The previously known 2-phenyl-3H-quinazolin-4-thiones
were prepared by a new method using other reagents, and the yields were comparable with those
given in literature. Our synthetic approach has the advantage in that it offers the possibility of
controlling the course of the cyclisation reaction that can involve the attack of carbonyl group either
by sulphur atom or by nitrogen atom depending on the medium used. The reaction conditions were
optimised so as to prevent the subsequent desulphuration reaction. 1-Methyl-2-phenylquinazolin-4-
thiones exclusively occur in their 1H thioketone form whereas the analogous 2-phenylquinazoline-4-
thiones are predominantly present in their 3H thioketone form, the tautomeric form being
independent of the medium (solid phase, solution). The antituberculotic, antialgal and antimycotic
activities of the 2-benzoylaminothiobenzamides and 2-phenylquinazoline-4-thiones have been tested,
and will be reported in a specialised journal.
Acknowledgements
The authors thank the Ministry of Education, Youth and Sports of the Czech Republic for
financial support (Project CI MSM 253 100 001).
Experimental
General
1
13
The H- and C-NMR spectra were measured at 360.14 and 90.57 MHz, respectively, at 25 °C,
using a Bruker AMX spectrometer. Compounds 1a-m and 2a-m were measured as saturated solutions
in hexadeuteriodimethyl sulphoxide (DMSO-d6), and the chemical shifts are referenced to
tetramethylsilane (δ(1H) = 0) and the solvent signal (δ(13C) = 39.6). The CH, CH3, and Cquart groups
in 13C-NMR spectrum were differentiated by means of the APT method.
The IR spectra were measured in Nujol using a Perkin–Elmer 684 apparatus and a KBr cell. The
Raman spectra were measured in dimethyl sulphoxide using a Bruker IFS 55 apparatus with an FRA
106 extension. For the source we used the Nd:YAG laser with the excitation frequency of 9394 cm–1.
The mass spectra were measured with a VG Platform II mass spectrometer (Micromass,
Manchester, UK) using chemical ionisation at atmospheric pressure (APCI) and a quadrupole
analyser (0-3000 Da). Before the mass spectrometer there was inserted a separation apparatus
consisting of a Waters 616 high-pressure pump, Waters 717 autosampler and a Waters 966 UV

Molecules 2001, 6
328
detector (all from Waters, Milford, USA), and a Separon SGX C18 octadecyl silica glass cartridge
column (150 × 3 mm i.d., 7 µm particle size; Tessek Ltd., Prague, Czech Republic). A mixture of
70% acetonitrile and 30% redistilled water was used as the mobile phase. The effluent from the liquid
chromatography was directly introduced into a quadrupole mass spectrometer equipped with APCI
probe operated in positive ion mode. The data was acquired in the m/z range 15-600 at 1.9 s per scan.
In the APCI mode, the temperature of the ion source and of the probe were 100 and 500°C,
respectively. The cone voltage was set at 10 V for positive-ion APCl.
2-Aminothiobenzamide
A 250-mL flask was charged with 2-aminobenzamide (13.6g, 0.1 mol), phosphorus penta-
sulphide (22.3g, 0.1 mol) and pyridine (70 mL). The mixture was refluxed 1.5 h, whereupon it was
cooled and poured onto ice water (250 mL). The separated yellow crystals of the pyridinium salt of 2-
mercapto-2-thioxo-2,3-dihydro-1H-2λ5-benzo[1,3,2]diazaphophinine-4-thione were collected by
filtration and recrystallised from a mixture of water and dimethylformamide (5:1). Yield 20.8g (64%)
yellow crystals, m.p. 190-201 °C.
A 500-mL flask was charged with the pyridinium salt of 2-mercapto-2-thioxo-2,3-dihydro-1H-
2λ5-benzo[1,3,2]diazaphophinine-4-thione (19.5g, 0.06 mol) along with water (70 mL), toluene (70
mL), and conc. hydrochloric acid (1.3 mL). The reaction mixture was refluxed until the solid portion
completely dissolved and then for another 4 h, whereupon it was cooled to room temperature, and the
separated crystals were collected by filtration and recrystallised from water. Yield: 5g (54.6%) yellow
crystals, m.p. 118-121 °C (in agreement with ref. [16]).
2-Methylaminothiobenzamide
This substance was prepared in the same way as 2-aminothiobenzamide. The first step gave 23.5g
(69%) of the pyridinium salt of 1-methyl-2-mercapto-2-thioxo-2,3-dihydro-1H-2λ5-
benzo[1,3,2]diaza-phophinine-4-thione, m.p. 165-170 °C. The second step (hydrolysis of this salt)
gave 7.9g (79.1%) 2-methylaminothiobenzamide, m.p. 114-115 °C (in agreement with ref. [17]).
2-Amino-N-methylthiobenzamide
This substance was prepared in the same way as 2-aminothiobenzamide. The first step gave 20g
(59%) of the pyridinium salt of 3-methyl-2-mercapto-2-thioxo-2,3-dihydro-1H-2λ5-benzo[1,3,2]-
diazaphophinine-4-thione, m.p. 145-150 °C (ref. [7] gives m.p. 168-169 °C). The second step
(hydrolysis of this salt) gave 6.3g (64.3%) 2-amino-N-methylthiobenzamide, m.p. 96-98 °C (in
agreement with ref. [18]).
2-Benzoylaminothiobenzamides 1a-m

Molecules 2001, 6
329
A 100-mL three-necked flask equipped with a magnetic stirrer, dropping funnel, and argon inlet
was charged with the appropriate thioamide (10 mmol), dry acetone (40 mL), and triethylamine (10
mmol). The solution formed was treated with the corresponding benzoyl chloride (10 mmol)
dissolved in acetone (10 mL), added within ca. 5 min. The reaction mixture was stirred under an
argon atmosphere at room temperature 0.5-1 h. The separated triethylamine hydrochloride was
collected by filtration on a pressure filter (sintered glass), and the filtrate was evaporated in vacuum at
room temperature. The evaporation residue was mixed with ice-cold methanol (10 mL). The
separated crystals were collected under argon and carefully washed with ice-cold methanol (3×10
mL). If the product thus obtained did not possess the required quality, it was recrystallised from
1
methanol at room temperature (max. 25 °C). The yields, melting points, and H- and 13C-NMR
spectra are summarised in Tables 1 - 5.
2-Phenylquinazoline-4-thiones 2a-m
A 100-mL flask was charged with the appropriate 2-benzoylaminothiobenzamide 1a-m (2 mmol)
and ethanol (50 mL). The solution formed was treated with 1M sodium methoxide (1 mL), and the
reaction mixture was refluxed 1 h, whereupon it was neutralised with acetic acid to pH ~ 7 and
concentrated to crystallisation. The crystalline product obtained on cooling was recrystallised from
1
13
toluene, methanol, or dimethylformamide. The yields, melting points, H- and C-NMR spectra are
summarised in Tables 6 - 10.
2-Benzoylamino-N-methylthiobenzamide
This substance was prepared in the same way as the 2-benzoylaminothiobenzamides 1a-m. The
yield of the product thus obtained was 1.7g (62%), m. p. 192-193 °C. 1H-NMR (δ): 3.18 (s, 3H, CH3),
7.28 (m, 1H, H-3), 7.41 (m, 1H, H-5), 7.53 (m, 1H, H-4), 7.58 – 7.68 (m, 3H, H-m + H-p), 7.95 (m,
2H, H-o), 8.20 (m, 1H, H-2), 10.78 a 10.86 (2×bs, 2H, NH).
2-Phenyl-3-methylquinazoline-4-thione
The preparation was the same as that used for 2-phenylquinazoline-4-thiones 2a-m. Yield 0.4g
(80%), m. p. 134-136 °C. 1H-NMR (δ): 3.85 (s, 3H, CH3), 7.60 – 7.64 (m, 3H, H-m +H-p), 7.67 (m,
13
1H, H-3), 7.75-7.79 (m, 3H, H-o + H-5), 7.94 (m, 1H, H-4) 8.74 (m, 1H, H-2). C-NMR (δ): 43.8
(CH3), 128.9 (C-4a), 128.9 (C-8), 129.2 (C-m), 129.3 (C-6), 129.4 (C-o), 130.8 (C-5), 131.0 (C-p),
135.6 (C-7), 136.7 (C-i), 143.0 (C-8a), 156.0 (C-2), 188.9 (C=S).
Ring Closure of 1a in Sulphuric Acid
A 50-mL flask was charged with 2-benzoylaminothiobenzamide (1a, 0.5 g, 1.95 mmol) together
with 96% sulphuric acid (5 mL) and acetic anhydride (3 mL). The mixture was stirred at room
temperature 3 days, whereupon it was poured onto crushed ice (50g). The separated crystals were
collected by suction, washed with water, with 10% aqueous sodium bicarbonate (30 mL), and again
with water. One major and two minor components were identified by means of HPLC-MS. The

Molecules 2001, 6
330
minority components were identified as: (1) the starting material, 2-benzoylaminothiobenzamide
(1a), MS (m/z,%): [M+H]+ - (257.1, 93); [M–H2S+H]+ - (223.1, 100) and (2) 2-phenyl-4-imino-
benzo[d-1,3] MS (m/z,%): [M+H]+ - (239.1, 100); [M–H2S+H]+ - (205.0, 12). The major component
was 2-phenylbenzo[d-1,3]thiazin-4-one MS (m/z): [M+H]+ - (240.1).
Ring Closure of 1a in Anhydrous Phosphoric Acid
A 50-mL flask was charged with 2-benzoylaminothiobenzamide (1a, 0.5 g, 1.95 mmol) together
with anhydrous phosphoric acid (10 mL, 85% H3PO4 + 6.7 g P2O5). The mixture was stirred at room
temperature 14 days. Then it was poured onto crushed ice (50g) and the separated crystalline solid
was collected by suction, washed with water, with 10% aqueous sodium bicarbonate (30 mL), and
again with water. The filter cake was suspended in 50% aqueous methanol (60 mL) and refluxed 30
min. The crystalline solid separated on cooling was collected by suction and recrystallised from
methanol with addition of charcoal. Yield 0.23g (49%) long yellowish needles, m.p. 113-116 °C (ref.
[19] gives m.p. 116 °C). MS (m/z): [M+H]+ - 240.1.
S
C
NH2
R2
N C
R1
O
1a - 1m
Table 1 – Melting points and elemental analyses of the 2-(3 and 4-subst. benzoylamino)-
thiobenzamides.
m.p.*
(°C)
Elemental analysis
Formula
M.W.
Calculated/Found (%)
Compound
R1
R2
Yield (%)
C
H
N
S
X
H
H
182-184
48
205-210
44
75-80
60
C14H12N2OS 65.60 4.72 10.93 12.51
256.32 65.48 4.79 10.89 12.59
C15H14N2OS 66.64 5.22 10.36 11.86
270.34 66.76 5.12 10.20 11.60
C15H14N2O2S 62.92 4.93
286.34 62.83 5.02
1a
1b
1c
1d
1f
H
H
4-CH3
4-OCH3
4-Cl
9.78 11.20
9.82 11.31
H
110-112 C14H11ClN2OS 57.83 3.81
9.63 11.03 12.19
9.45 11.29 12.03
48
170-180
34
144-149
41
290.76
57.52 3.75
H
3-NO2
H
C14H11N3O3S 55.81 3.68 13.95 10.64
301.31 55.65 3.54 13.97 10.75
C15H14N2OS 66.64 5.22 10.36 11.86
270.34 66.58 5.35 10.30 11.96
CH3
1g

Molecules 2001, 6
331
CH3
4-CH3
163-165
34
C16H16N2OS 67.58 5.67
284.37 67.41 5.80
C16H16N2O2S 63.98 5.37
300.37 64.12 5.22
9.85 11.27
9.71 11.09
9.33 10.67
9.45 10.76
1h
1i
CH3 4-OCH3 150-153
50
CH3
CH3
CH3
CH3
4-Cl
155-162 C15H13ClN2OS 59.11 4.30
40 304.79 59.03 4.12
175-180 C15H13BrN2OS 51.59 3.75
9.19 10.52 11.63
9.26 10.64 11.47
1j
3-Br
8.02
7.95
9.18 22.88
9.30 22.65
1k
1l
33
139-140
35
349.24
51.74 3.73
4-NO2
3-NO2
C15H13N3O3S 57.13 4.16 13.33 10.17
315.34 57.33 4.31 13.21 10.00
C15H13N3O3S 57.13 4.16 13.33 10.17
315.34 57.29 4.27 13.17 10.05
180-184
1m
32
*All the melting points are with decomposition
S
2
C
3
NH2
o
o
m
m
4
R2
N C
R1
5
O
Table 2 – 1H-NMR chemical shifts of the 2-(4-subst.benzoylamino)thiobenzamidesa
Compd.
1a
H-2
8.25
m; 1H
8.26
m; 1H
8.27
m; 1H
8.17
H-3
7.27
H-4
7.54
m; 1H
7.52
m; 1H
7.52
m; 1H
H-5
7.48
m; 1H
7.47
m; 1H
7.47
m; 1H
H-o
8.00
m; 2H
7.88
m; 2H
7.96
m; 2H
7.99
m; 2H
7.58
m; 2H
7.00
m; 2H
7.53
m; 2H
7.57
H-m
7.61
m; 2H
7.42
m; 2H
7.15
m; 2H
7.69
m; 2H
NH2
R1
R2
9.93 + 10.37 11.23 7.67
2×bs; 2H bs;1H m;1H
9.92 + 10.33 11.15 2.44
2×bs; 2H bs;1H s; 3H
9.91 + 10.34 11.13 3.89
2×bs; 2H bs;1H s; 3H
9.89 + 10.32 11.20
m; 1H
7.25
1b
1c
1d
1g
1h
1i
m; 1H
7.24
m; 1H
7.28
← 7.48 - 7.55 →
m; 1H
←
m; 1H
m; 2H
2×bs; 2H bs;1H
7.18 - 7.30
m; 3H
→
→
→
→
6.94
m; 1H
6.93
m; 1H
6.96
m; 1H
7.04
m; 1H
→
7.18-7.30 9.51 + 10.09 3.33 7.18-
m; 2H
7.47
2×bs; 2H s; 3H 7.30
9.49 + 10.08 3.31 2.26
2×bs; 2H s; 3H s; 3H
9.48 + 10.04 3.51 3.74
2×bs; 2H s; 3H s; 3H
←
←
←
←
7.18 - 7.28
m; 3H
7.18 - 7.30
m; 3H
7.23 - 7.30
m; 3H
m; 2H
6.76
m; 2H
7.23-7.30 9.52 + 10.09 3.34
1j
m; 2H
8.06
m; 2H
m; 2H
7.76
m; 2H
2×bs; 2H s; 3H
9.36 + 10.01 3.38
2×bs; 2H s; 3H
7.21 - 7.32
m; 4H
1l

Molecules 2001, 6
332
S
C
2
R2
3
4
NH2
8
7
10
N C
5
R1
O
12
11
Table 3 – 1H-NMR chemical shifts of the 2-(3-subst.benzoylamino)thiobenzamides
Compd. H-2
H-3
7.31
H-4
H-5
H-8
8.81
H-10 H-11 H-12
8.49 7.91
NH2
R1
8.10
7.52 - 7.57
8.40 9.86 + 10.28 11.33
2×bs; 2H bs;1H
7.49 9.58 + 10.15 3.36
m; 1H m; 1H s; 1H m; 1H m; 1H m; 1H 2×bs; 2H s; 3H
7.93 9.39 + 10.04 3.40
1f
1k
1m
m; 1H m; 1H
m; 2H
s; 1H m; 1H m; 1H m; 1H
7.83 7.58 7.18
←
7.31
→
7.24
7.05
m; 2H
←
7.24 - 7.33
m; 4H
→
8.34
8.18
7.54
s; 1H m; 1H m; 1H m; 1H
2×bs; 2H
s; 3H
S
C
2
1
6
3
4
NH2
o
o
m
m
R2
i
N C
p
5
R1
O
Table 4 – 13C-NMR chemical shifts of the 2-(4-subst.benzoylamino)thiobenzamides
R1
No. C-1 C-2 C-3 C-4 C-5 C-6 C=S C=O C-i C-o C-m C-p
R2
134.5 127.2 124.0 130.5 122.9 135.4 199.4 164.7 132.2 127.4 129.0 132.2
131.9 127.1 123.8 130.5 122.6 135.6 199.4 164.5 131.7 127.4 129.5 142.3
131.8 127.0 123.6 131.0 122.5 135.6 199.3 164.7 126.5 129.2 114.2 162.3
131.2 127.2 124.2 130.5 123.1 135.2 199.3 163.7 132.5 129.0 129.3 137.0
1a
1b
1c
1d
1g
1h
1i
21.2
55.6
138.8 129.4 127.3 129.6 127.1 140.9 200.7 169.1 136.0 127.5 128.6 129.9 38.0
139.2 129.4 127.3 129.8 127.0 141.1 200.7 169.1 133.1 128.0 128.8 138.9 38.0 21.0
138.9 129.6 127.3 130.8 127.0 141.4 200.7 168.9 128.1 129.6 112.8 160.2 38.3 55.2
139.0 129.7 127.6 129.8 127.3 140.7 200.4 168.1 134.3 130.5 130.5 134.9 38.1
139.3 129.8 127.8 130.0 127.3 140.2 200.0 167.3 142.2 129.7 122.8 147.7 38.2
1j
1l
13
Note: The C-NMR shifts of carbon with close values of chemical shifts (C-3 and C-5) can be
interchanged.

Molecules 2001, 6
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S
C
2
R2
1
3
4
NH2
8
7
6
10
N C
5
R1
O
12
11
Table 5 – 13C-NMR chemical shifts of the 2-(3-subst.benzoylamino)thiobenzamides
No. C-1 C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-11 C-12 C=S C=O
133.7 127.4 124.7 130.6 122.3 136.0 134.7 123.7 148.0 126.5 130.4 133.7 199.4 162.8
138.9 129.7 127.5 129.9 127.4 140.5 138.2 129.6 120.9 132.4 131.4 127.4 200.5 167.5
139.3 129.8 127.7 130.0 127.4 140.3 137.4 123.5 147.0 124.4 129.2 134.9 200.1 166.8
1f
1k
1m
Note: The signal of N-CH3 group was always at 38.1 ppm. The 13C-NMR shifts of carbon with close
values of chemical shifts (C-3 and C-5) can be interchanged.
S
N
N
R2
R1
Table 6 – Melting points and elemental analyses of the 2-(3- and 4-
subst.phenyl)quinazoline-4-thiones 2a-m
m.p.
(°C)
Elemental analysis
Calculated./Found (%)
Compound
R1
H
H
H
H
H
H
R2
H
Formula
M.W.
C14H10N2S
238.30
C15H12N2S
252.33
Yield (%)
221-223a
88
C
H
N
S
X
70.56 4.23 11.76 13.45
70.39 4.39 11.82 13.49
71.40 4.79 11.10 12.71
71.15 4.72 11.21 12.57
2a
2b
2c
2d
2e
2f
4-CH3
221-222a
86
4-OCH3 200-201a
85
C15H12N2OS 67.14 4.51 10.44 11.95
268.33 67.20 4.31 10.35 11.65
C14H9ClN2S 61.65 3.33 10.27 11.75 13.00
272.75 61.52 3.35 10.11 11.68 13.03
C14H9N3O2S 59.35 3.20 14.83 11.32
283.30 59.10 3.30 15.04 11.39
C14H9N3O2S 59.35 3.20 14.83 11.32
283.30 59.27 3.24 14.93 11.20
4-Cl
287-289a
83
4-NO2
3-NO2
250-252b
89
263-265
84

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CH3
CH3
H
197-199
91
237-239
87
95-98
84
249-251
89
252-254
81
264-266
85
278-280
80
C15H12N2S
252.33
C16H14N2S
266.36
71.40 4.79 11.10 12.71
71.20 4.70 11.21 12.86
72.15 5.30 10.52 12.04
72.15 5.39 10.38 12.41
2g
2h
2i
4-CH3
CH3 4-OCH3
C16H14N2OS 68.06 5.00
282.35 67.95 5.10
C15H11ClN2S 62.82 3.87
286.77 62.74 3.93
C15H11BrN2S 54.39 3.35
331.22 54.77 3.41
C15H11N3O2S 60.59 3.73 14.13 10.78
297.33 60.05 3.87 14.42 10.92
C15H11N3O2S 60.59 3.73 14.13 10.78
297.33 60.87 3.44 13.96 10.86
9.92 11.35
9.86 11.48
9.77 11.18 12.36
9.73 10.95 12.29
CH3
CH3
CH3
CH3
4-Cl
3-Br
2j
8.46
8.38
9.68 24.12
9.46 24.00
2k
2l
4-NO2
3-NO2
2m
a In agreement with ref. [20]
b In agreement with ref. [21]
S
2
3
4
N
o
m
N
5
R1
R2
o
m
Table 7 – 1H-NMR chemical shifts of the 2-(4-subst.phenyl)quinazoline-4-thiones
Compd.
2aa
H-2
8.66
m; 1H
8.65
m; 1H
8.64
m; 1H
8.66
m, 1H
8.68
m; 1H
8.67
H-3
7.58-7.67
m; 1H
7.63
m; 1H
7.60
m; 1H
7.63-7.70
m; 1H
7.69
m; 1H
7.80-7.82
m; 2H
H-4
7.94
m; 1H
7.94
m; 1H
7.92
m; 1H
7.94
m; 1H
7.99
m; 1H
7.99
H-5
7.82
m; 1H
7.81
m; 1H
7.78
m; 1H
7.83
m; 1H
7.87
m; 1H
7.88
H-o
8.20
m; 2H
8.14
m; 2H
8.22
m; 2H
8.24
H-m
7.58-7.67
m; 2H
7.42
m; 2H
7.15
m; 2H
7.63-7.70
m; 2H
R1
R2
7.58-7.67
m; 1H
2.46
13.96
bs; 1H
13.88
bs; 1H
13.80
bs; 1H
14.02
bs; 1H
14.25
bs; 1H
3.75
2b
2c
2d
2e
2g
s; 3H
3.90
s; 3H
m; 2H
←
8.44
m; 4H
→
←– 7.63 - 7.68 –→
7.80-7.82
m; 2H
m; 1H
m; 1H
m; 1H
m; 4H
s; 3H

Molecules 2001, 6
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8.66
m; 1H
8.66
m; 1H
8.67
m; 1H
8.69
7.66
m; 1H
7.65
m; 1H
7.67
m; 1H
7.70
7.96
m; 1H
7.97
m; 1H
7.99
m; 1H
8.02
7.87
m; 1H
7.87
m; 1H
7.89
m; 1H
7.93
7.72
m; 2H
7.82
m; 2H
7.86
m; 2H
8.48
7.45
m; 2H
7.19
m; 2H
7.72
m; 2H
8.10
3.79
s; 3H
3.83
s; 3H
3.77
s; 3H
3.74
2.47
s; 3H
3.92
2h
2I
2j
2l
s; 3H
m; 1H
m; 1H
m; 1H
m; 1H
m; 2H
m; 2H
s; 3H
a In agreement with ref. [22]
S
2
5
3
4
N
9
R2
N
R1
13
11
12
Table 8 – 1H-NMR chemical shifts of the 2-(3-subst.phenyl)quinazoline-4-thiones
Compd.
2f
H-2
8.65
m; 2H
8.67
H-3
7.67
m; 1H
7.68
H-4
7.96
m; 1H
8.00
H-5
7.88
m; 2H
7.88
H-9
9.04
m; 1H
8.00
H-11
8.65
m; 2H
7.82
H-12
7.88
m; 2H
7.60
H-13
8.48
m; 1H
7.88
R1
14.27
bs; 1H
3.77
2k
m; 1H
8.69
m; 2H
m; 1H
7.70
m; 1H
m; 2H
8.02
m; 1H
m; 2H
7.94
m; 2H
m; 2H
8.69
m; 2H
m; 1H
8.51
m; 1H
m; 1H
7.94
m; 2H
m; 2H
8.27
m; 1H
s; 3H
3.78
s; 3H
2m
S
2
5
1
3
4
N
o
i
m
6
7
N
R1
p
R2
o
m
Table 9 – 13C-NMR chemical shifts of the 2-(4-subst.phenyl)quinazoline-4-thiones
No. C-1 C-2 C-3 C-4 C-5 C-6 C=S C-7 C-i C-o C-m C-p
R1
R2
2aa 127.8 129.5 128.3 135.7 128.2 144.5 188.0 151.7 132.3 128.7 128.6 131.7
127.6 129.4 128.2 135.5 127.9 144.5 188.0 151.5 129.4 128.5 129.2 141.8
21.1
2b

Molecules 2001, 6
336
127.4 129.4 128.0 135.5 127.6 144.5 187.9 151.1 124.2 130.3 114.0 162.1
55.6
2c
2d
2e
2g
2h
2i
127.7 129.4 128.2 135.5 128.1 144.3 188.2 150.8 131.3 130.4 128.6 136.4
128.0 129.4 128.7 135.6 128.5 144.1 188.1 150.3 138.4 130.2 123.6 149.1
128.1 130.6 127.5 134.7 117.7 137.5 199.0 154.9 134.5 129.4 128.6 130.8 38.8
128.1 130.6 127.3 134.6 117.6 137.6 198.9 154.9 131.5 129.1 129.6 140.9 38.9 21.2
128.0 130.5 127.1 134.4 117.6 137.7 198.7 154.5 126.2 131.8 113.9 161.4 39.2 55.6
128.2 130.5 127.5 134.6 117.6 137.4 198.9 153.9 133.3 131.4 128.6 135.6 38.7
128.3 130.6 127.8 134.9 117.7 137.3 199.0 153.2 140.6 130.9 123.7 146.6 38.6
2j
2l
a Assignment and values are in agreement with ref. [22]
S
2
1
3
N
9
R2
10
8
4
6
7
N
5
R1
13
11
12
Table 10 – 13C-NMR chemical shifts of the 2-(3-subst.phenyl)quinazoline-4-thiones
No. C-1 C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-11 C-12 C-13 C=S
128.0 129.4 128.5 135.4 128.4 144.1 150.0 134.0 123.5 147.8 126.0 130.2 134.9 188.1
128.3 130.6 127.7 134.8 117.7 137.4 153.5 136.7 131.9 121.7 133.6 130.8 128.4 199.0
128.1 130.6 127.7 134.8 117.8 137.5 153.0 136.1 124.5 147.7 125.3 130.3 135.7 199.0
2f
2k
2m
The signal of N-CH3 group was always at 38.8 ppm.
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