One-pot quinazolin-4-yl-thiourea synthesis via N-(2-cyanophenyl)benzimidoyl isothiocyanate

Article abstract of DOI:10.3390/60700588

1-substituted-3-(2-phenylquinazolin-4-yl) thioureas (7) were produced by an intramolecular cycloaddition reaction of 1-substitued-3-[(2-cyanophenylimino) phenylmethyl] thioureas (3). These compounds in turn were prepared by the reaction of N-(2-cyanophenyl)benzimidoyl isothiocyanate (2) with primary amines. The structures of products 7 were confirmed by FTIR, ¹H-NMR, ¹³C-NMR, mass spectroscopy and X-ray crystallography.

Full text of DOI:10.3390/60700588

Molecules 2001, 6, 588-602
molecules
ISSN 1420-3049
http://www.mdpi.org
One-Pot Quinazolin-4-yl-thiourea Synthesis via N-(2-Cyano-
phenyl)benzimidoyl isothiocyanate
Fathalla, W.1, Čajan, M. 1,2, Marek, J. 3 and Pazdera, P.1,*
1 Department of Organic Chemistry, Faculty of Science, Masaryk University, Brno, Czech
Republic, Tel.: +420 5 41129305, Fax: +420 5 41211214,
2 Laboratory of Biomolecular Structure and Dynamics, Faculty of Science, Masaryk University,
Brno, Czech Republic.
3
Department of Inorganic Chemistry, Masaryk University, 611 37 Brno, Czech Republic.
*Author to whom correspondence should be addressed; E-mail: pazdera@chemi.muni.cz
Received: 10 November 2000; in revised form 22 May 2001 / Accepted: 23 May 2001 / Published:
30 June 2001
Abstract: 1-substituted-3-(2-phenylquinazolin-4-yl) thioureas (7) were produced
by an intramolecular cycloaddition reaction of 1-substitued-3-[(2-cyanophenyl-
imino)phenylmethyl] thioureas (3). These compounds in turn were prepared by the
reaction of N-(2-cyanophenyl)benzimidoyl isothiocyanate (2) with primary amines.
1
13
The structures of products 7 were confirmed by FTIR, H-NMR, C-NMR, mass
spectroscopy and X-ray crystallography.
Keywords: 1-(2-phenylquinazolin-4-yl)-3-substituted thioureas; 1-[(2-cyano-
phenylimino)phenylmethyl]-3-substituted
thioureas;
N-(2-cyanophenyl)-
benzimidoyl isothiocyanate; one-pot synthesis; amidinoyl isothiocyanates.
Introduction
This work is a continuation of our studies of the competition between the sulfur and nitrogen
atoms in a thioamide moiety towards intermolecular and intramolecular reactions with electrophiles
[1-3]. The intramolecular cycloaddition reaction of the product formed in situ by addition of

589
Molecules 2001, 6
secondary amines to N-(2-cyanophenyl)benzimidoyl isothiocyanate affords 1,1-disubstituted-3-(2-
phenyl-3H-quinazolin-4-ylidene)thioureas [3]. These cyclic products are formed via a one-pot
reaction sequence including cyclization, Dimroth rearrangement and tautomerisation steps, as
reported in [3].
Results and Discussion
The extension of such a reaction to include primary amines, anilines, heterocyclic amines, and
adamantanamine derivatives is now reported in this paper. The reaction proceeds by the addition of
primary amines to N-(2-cyanophenyl)benzimidoyl isothiocyanate (2) to predictably give the
thiourea derivatives 3 [3] (Scheme 1).
S
C
N
C
N
a
C
N
Cl
N
N
1
2
3
6
b
HN
R
S
C
C
N
N
S
N
R
H
H
NH
N
N
N
4
HN
R
S
C
NH
N
N
R
S
NH
N
N
H
N
5
a: KSCN, acetone, -5°C, 2h; b: NH2R, acetone, 25°C, 24 h.
Scheme 1. Reaction of the 2 with primary amines and possible reaction pathways

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Molecules 2001, 6
These thioureas 3 contain three active nucleophilic sites capable of attacking the available
nitrile group via an intramolecular cycloaddition reaction. The expected products might conceivably
be one or all of the following cyclic products: benzothiadiazocine derivatives (4) arising via sulfur
attack [4-6], quinazoline derivatives (6) via nitrogen attack [3] or finally the benzotriazocines (5)
via nitrogen attack The reaction could be further extended to involve the Dimroth rearrangement
product or could involve tautomerisation to the more stable tautomer [3].
The intramolecular addition reaction of thioureido derivatives containing functionalized
carboxyl groups under neutral and basic conditions takes place on the nitrogen atom [7-8].
Consequently, the expected products formed were either the quinazoline 6 or the benzotriazocine 5
derivatives. Of these two options we might expect the quinazoline derivative 6 to be more favored
due to the fact that their formation involves creation of a thermodynamically more stable six
membered ring. The expected quinazoline derivative 6 might then undergo a Dimroth
rearrangement to finally afford the 1-(2-phenylquinazolin-4-yl)-3-substituted thioureas 7. The
quinazolines 7 can be stabilized by hydrogen bond interactions to afford an extra six membered ring
as shown in Scheme 2. These compounds 7 could undergo a tautomerisation reaction by the
transition of the proton of the N(1) of the substituted thioureas to N(3) of the quinazoline ring to
give either of the conformations 8 or 9 that might also be stabilized by hydrogen bond interactions
(Scheme 2).
S
R
S
H
NH
N
N
N
N
H
R
C
N
N
N
H
7
6
R
H
S
N
R
N
S
N
N
N
H
H
H
N
N
N
9
8
Scheme 2. Possible interconversions from 6 to 9 via Dimroth rearrangement and
tautomerisation processes.

591
Molecules 2001, 6
The spectral data confirmed that the structures of the isolated products were indeed 7. The
secondary amine examples behaved differently, undergoing tautomerisation to give the more stable
tautomer to thus afford 1,1-disubstituted-3-(2-phenyl-3H-quinazolin-4-ylidene)thioureas [3].
Discrimination between the possible structures of compounds 4-9 was possible using their spectral
data as follows: the infrared spectra show both the disappearance of the ν(NCS) and ν(CN) bands
present in case of the isothiocyanate 2 and the presence of νNH and ν(C=N) bands at 3220 cm-1 and
1613 cm-1, respectively, for the cyclic forms 7.
The most important peak shown by the 13C-NMR, which plays an important role in the structure
identification of the cyclic products, is the one corresponding to the C=S group with a chemical
shift of ca 183-184 ppm. Naturally, it is observed in the case of the quinazoline structures 6-9 and
the benzotriazocines 5 but not the thiadiazocines 4.
1
The H-NMR spectra show great similarity to the simulated computer spectra; they display an
important peak at ca 14 ppm (in the case of the substituted anilines) corresponding to the NH group,
which together with X-ray analysis, confirms the hydrogen bond interactions between the
quinazoline N(3) and the hydrogen atom of the arylamino group (Scheme 2). The spectra in the case
of the aliphatic analogues displayed a peak at ca 12 ppm corresponding to the hydrogen of the
alkylamino group. We might expect that the peaks corresponding to NH groups that have
interactions with the thiocarbonyl group as in 8 will appear at ca 16 ppm as in the case of secondary
1
amine analogues [3]. The H-NMR spectrum of product 7f (R= Ph) was measured in CDCl3 at
temperature ranging from -30°C to 30°C in order to check whether these three conformers 7-9
1
interconvert or not, but no changes were observed in the resultant spectra. The H-NMR spectrum
of 7b gave a doublet peak at ca 4.98 ppm due to the interaction between the CH2 group and the
1
neighboring NH group. Measurement of the H-NMR spectrum in CDCl3/D2O, to give a singlet
peak at ca 4.97 ppm, proved this.
The mass spectra for all examined products 7 showed the molecular ion, followed by a
molecular fragment at m/e 33 which represents the SH moiety and the tricyclic residue of the
isolated product at m/e 337 of compound 7g (R= p-tolyl). This last result confirms that the sulfur
atom is exocyclic unlike the secondary amine examples where such a fragment is not formed
indicating that the sulfur atom is endocyclic. Other fragmentations are represented in Figure 1
106
CH3
150
S
CH3
CH3
165
S
S
H
N
N
N
H
H
N
N
N
H
H
N
N
N
H
N
N
N
265
221
205
Figure 1. Mass spectral fragmentations of 7g.

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Molecules 2001, 6
Single crystals of 7f, 7a and 7b (R= Ph, n-butyl and benzyl, respectively) were used for X-ray
analysis [9]. These substituents cover a range of different types to ensure that the structure of the
final product is not dependent on the substituent, or the basicity of the amines compared to the
anilines [3]. The structural data presented in Tables 1-3 correspond to a great extent with those
calculated by the ab initio DFT quantum chemistry methods for 7f (R= Ph) [9]. The ORTEP
diagram and the calculated model of compound 7f are shown in Figures 2 and 3, respectively.
Figure 2: The ORTEP diagram of compound 7f.
Figure 3: The calculated model of compound 7f.

593
Molecules 2001, 6
The X-ray structural analysis shows that the isolated products correspond to the Dimroth
rearrangement products 7 and not to the two possible tautomeric conformations 8 and 9. The ab
initio computational studies together with the X-ray analysis show that the compound 7f (R= Ph) is
almost planar having the phenyl ring at position 2 slightly out of plane. The C(15) carbon of the
phenylthiourea together with the thiourea moiety and the quinazoline cycle are almost in one plane.
The π-electrons are in good conjugation as depicted in Figure 3. The hydrogen bond interactions
between the NH group and the N(3) of the quinazoline ring add extra stability to the isolated
product 7f (Scheme 2). These hydrogen bond interactions were identified from the X-ray analysis
and the computational studies, which show a bond distance of about 1.86 Å and 1.94 Å,
respectively.
There were no great energy differences between the two structures 7f (–891009.73 kcal.mol-1)
and 8f (–891006.05 kcal.mol-1). This led us to the conclusion that the sulfur atom could be involved
in intermolecular hydrogen interactions. However, the probability of this conclusion was decreased
after measuring the 1H-NMR at a temperature ranging from –30 °C to 30 °C, which gave the same
spectra. The other conclusion, based on the reaction sequence reported in Scheme 2, is that the
major product is the one that is formed first, which identify the formation of the Dimroth
rearrangement product as the first step and is the isolated product. On the contrary in the secondary
amine application [3], the Dimroth rearrangement product is not stabilized by hydrogen interactions
so it is less stable than the tautomeric form which have hydrogen bond interactions between the N3
hydrogen and the thiocarbonyl group.
Table 1. Selected interatomic distances in 7f.
Bond Length [Å]
Bond Length [Å]
X-ray HF/6-31G**
Bond
Bond
X-ray
HF/6-31G**
N1-C2
N1-C10
C2-N3
C2-C21
N3-C4
C4-N11
1.31
1.37
1.36
1.48
1.32
1.38
1.29
1.36
1.36
1.49
1.30
1.38
C4-C5
1.43
1.39
1.33
1.66
1.42
1.41
1.44
1.38
1.32
1.68
1.43
1.40
N11-C12
C12-N13
C12-S14
N13-C15
C5-C10
Table 2. The most important bond angles in 7f.
Angle [°]
X-ray
HF/6-31G**
Angle [°]
X-ray
HF/6-31G**
N1-C2-C21
C21-C2-N3
C2-N1-C10
N1-C2-N3
C2-N3-C4
N3-C4-N11
N3-C4-C5
119.2
115.2
116.3
125.6
118.6
118.7
121.4
118.4
116.5
116.0
125.1
118.9
120.1
121.5
N13-C12-N11
N13-C12-S14
C12-N13-C15
C16-C15-N13
C4-N11-C12
N1-C10-C5
114.9
127.6
131.5
115.8
130.7
122.8
120.8
116.8
126.4
126.8
118.4
132.7
122.3
119.7
C2-C21-C22

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Molecules 2001, 6
Torsion angle [°]
Table 3. The most important torsion angles in 7f.
X-ray
HF/6-31G**
Torsion angle [°]
X-ray
HF/6-31G**
S14-C12-N13-C15
N3-C2-C21-C22
N3-C4-N11-C12
C4-N11-C12-N13
N1-C2-C10-C5
C2-N1-C10-C9
1.16
157.74
-4.41
2.59
-1.12
177.17
0.2640
164.77
-3.338
0.0585
0.061
C10-N1-C2-C3
N1-C2- N3-C4
N1-C2-C21-C22
C2-N3-C4-C5
C2-N3-C4-N11
C4-N11-C12-S14
3.28
-1.38
-23.62
-2.76
177.88
-177.39
0.310
-0.331
-15.107
-0.026
179.752
-179.366
179.922
We confirmed the structures of the compounds 1-(2-phenylquinazolin-4-yl)-3-substituted
thioureas 7a-7s on the basis of the above spectral data, reference data from the computer simulated
spectra and from knowledge about the chemistry of the isothiocyanate derivative 2 [3].
Conclusions
1-substituted-3-(2-phenylquinazolin-4-yl) thioureas 7a-s were produced by a regioselective
intramolecular cycloaddition reaction of the nitrogen attack at the available nitrile group of the
thiourea derivatives 3.
Acknowledgments
This work was supported by a grant from the Ministry of Education of the Czech Republic
(Grant No. CEZ: J07/98:143100011) and from the Grant Agency of the Czech Republic (Grant No.
203/01/1333). We would like to thank the Analytical Department of Lachema Co., Brno, Czech
Republic for elemental analysis. The authors wish to acknowledge the Academic Supercomputer
Center in Brno for providing access to computer facilities.
Experimental
General
Melting points of all the compounds were measured on a Boetius Rapido PHMK 79/2106
(Wägetechnik) instrument. TLC was carried out on Silufol UV 254 plates (Kavalier, Votice). TLC
detection was accomplished with a Fluotes universal (Quarzlampen, Hanau) instrument and iodine
vapors. The eluent used was a (20: 80) mixture of acetone and benzene. Purity of compounds 7 was
proven by their elemental analysis, measured on an Erba 1102 instrument. FTIR spectra (results
-1
~
reported as ν /cm ) were taken on a Genesis (Unicam) spectrometer on potassium bromide pellets.
NMR spectra were measured on a Bruker Avance DRX-500 spectrometer. Unless stated otherwise
the 1H- and 13C-NMR spectra were measured in CDCl3 solutions and tetramethylsilane was used as
13
1
an internal standard. Results are reported in ppm on the δ scale. The measured C- and H-NMR
spectra were correlated with those obtained by on-line simulation (Advanced Chemistry

595
Molecules 2001, 6
Development, Inc., Toronto, Canada). The X-ray crystal data and structure refinement of compound
7f (Table 4) were collected with a KUMA KM-4 kappa four-circle diffractometer. The structure
was solved by direct methods using SHELXS86 [10] and refined on F2 for all reflections using
SHELXl93 [11]. Crystals suitable for X-ray determination were obtained in the form of white
prisms by recrystallization from CHCl3/petroleum ether at room temperature. The crystallographic
data for 7a, 7b and 7f have been deposited with the Cambridge Crystallographic Data Center as
supplementary publications number CCDC 149679 – 149681. Geometry optimization of structures
7a, 7b, and 7f was performed at ab initio level of quantum chemical calculation, RHF/6-316** and
DFT/VWN/6-316**, respectively. Mass spectra were determined (electron impact, 70 eV) with a
Fisons TRIO 1000 and GC 8000 series instrument.
Table 4: Crystal data and structure refinement for 7f.
Empirical formula
Molecular weight
Temperature, k
C21H16N4S
356.44
293(2) k
Wavelength, Å
0.71073 Å
Crystal system, space group
Unit cell dimensions
a, Å; α, °
monoclinic, P2 (1) / c
9.8405 (8) Å, α= 90 °
21.327 (2) Å, β= 95.710 (8) °
16.722 (2) Å, γ= 90 °
3492.0(5) Å3
b, Å; β, °
c, Å; γ, °
Volume, Å3
Z; density calculated, mg m-3
Absorption coefficient, mm-1
F(000)
8; 1.356 mg m-3
0.197 mm-1
1488
Crystal size, mm
θ Range for data collection,
Range of h, k, l
0.65 X 0.25 X 0.10 mm
3.50- 25.00°
-12< = h< =13, -27< = k< = 26,
-28< = l< = 21,
Reflections collected
Independent reflections
Refinement method
Data; restraints; parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
18128
6123 [R(INT) = 0.04231]
full-matrix least-squares on F2
5483 / 0 / 597
0.950
R1= 0.0462, wR2 = 0.1192
R1= 0.0818, wR2 = 0.1322
0.230 and –0.260 e. Å-3
Largest diff. Peak and hole

596
Molecules 2001, 6
N-(2-cyanophenyl)benzimidoyl isothiocyanate (2) - acetone solution.
A mixture of N-(2-cyanophenyl)benzamide [3] (0.5 g, 2.25 mmol), and phosphorous
pentachloride (0.5 g, 2.4 mmol) in dry toluene were refluxed for 8 h. The solvent was removed
under reduced pressure to give a brownish colored oil of N-(2-cyanophenyl)benzimidoyl chloride
(1) [3] which was not further purified. A solution of potassium thiocyanate (0.22 g, 2.25 mmol) in
dry acetone was added portionwise over 2 h to a stirred and cooled (-5°C) solution of crude 1 in dry
acetone. The precipitated potassium chloride was filtered off to give the acetone solution of N-(2-
cyanophenyl)benzimidoyl isothiocyanate (2). The IR spectrum of this solution displayed a strong
peak at 2059 cm-1 corresponding to the νNCS band. The isothiocyanate was used without further
isolation and purification (to avoid polymerization and destruction of this very reactive compound).
General procedure for the synthesis of 1-substituted–3-(2-phenylquinazolin-4-yl) thioureas (7).
The appropriate primary amine (2.25 mmol) was added portionwise while stirring at room
temperature over a period of 1h to the acetone solution of isothiocyanate 3. An additional amount of
triethylamine (0.6 ml, 4.5 mmol) was added in case of the adamantylamine hydrochloride examples
7q-7s. The reaction mixture was then stirred for 24h. The precipitated quinazoline thiourea 7 was
filtered off and recrystallized from ethyl alcohol. Spectral data are given below.
1-Butyl-3-(2-phenylquinazolin-4-yl) thiourea (7a).
(NH2R= butylamine); Yield: 0.21 g (29%); M.p. 165-166oC; Calc. for C19H20N4S (336.45): 67.83%
C, 5.99% H, 16.65% N, 9.53% S; Found: 67.64% C, 5.81% H, 16.48% N, 9.43% S; FTIR: 3427.6
(NH), 2952.8, 2928.0, 2869.2 (CH), 1618.2 (C=N); 1H-NMR: 12.16 (1H, s, NH), 8.79 (1H, s, NH),
8.24-7.48 (9H, m, ArH), 3.79-3.75 (2H, m, NHCH2), 1.83-1.76 (2H, m, NCH2CH2), 1.49-1.42 (2H,
m, HNCH2CH2CH2), 0.94 (3H, t, CH2CH3) (JA,B= 7.31 Hz); 13C-NMR: 180.11 (C=S), 158.90 (Cq),
156.16 (Cq), 151.57 (Cq), 137.70 (Cq), 134.57 (CHAr), 131.18 (CHAr), 129.89 (CHAr), 128.93
(CHAr), 128.38 (CHAr), 127.81 (CHAr), 120.67 (CHAr), 112.70 (Cq), 46.55 (NCH2), 31.05
(NCH2CH2), 20.60 (HNCH2CH2CH2), 13.99 (CH3); MS, m/z (Ir/%): 337 (24), 336 (71), 304 (15),
303 (82), 264 (58), 247 (28), 222 (59), 221 (100), 206 (37), 205 (89), 130 (15), 118 (38), 104 (25),
102 (36), 77 (50), 72 (18), 41 (17).
1-Benzyl-3-(2-phenylquinazolin-4-yl) thiourea (7b).
(NH2R= benzylamine); Yield: 0.3 g (36%); M.p. 189-190oC; Calc. for C22H18N4S (370.47): 71.33%
C, 4.90% H, 15.12% N, 8.65% S; Found: 71.24% C, 4.88% H, 15.03% N, 8.59% S; FTIR: 3292.1
(NH), 3024.58 (CH), 1619.81 (C=N); 1H-NMR: 12.31 (1H, s, NHCH2), 8.88 (1H, s, NH), 8.03-7.18
(14H, m, ArH), 4.98 (2H, d, NHCH2) (JA,B= 4.66 Hz); 13C-NMR: 179.82 (C=S), 158.90 (Cq),
156.00 (Cq), 151.36 (Cq), 136.89 (Cq), 136.49 (Cq), 134.62 (CHAr), 130.94 (CHAr), 129.77 (CHAr),
129.37 (CHAr), 129.20 (CHAr), 128.85 (CHAr), 128.59 (CHAr), 128.15 (CHAr), 127.83 (CHAr),

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Molecules 2001, 6
120.59 (CHAr), 112.57 (Cq), 51.31 (NCH2); MS, m/z (Ir/%): 371 (12), 370 (28), 339 (9), 337 (48),
264 (22), 263 (41), 239 (11), 222 (64), 221 (100), 206 (27), 205 (94), 149 (32), 118 (38), 104 (25),
102 (34), 91 (100), 77 (53), 65 (45), 51 (25).
1-Allyl-3-(2-phenylquinazolin-4-yl) thiourea (7c).
(NH2R= allylamine); Yield: 0.18 g (25%); M.p. 189-190oC; Calc. for C18H16N4S (320.41): 67.48%
C, 5.03% H, 17.49% N, 10.01% S; found: 67.32% C, 4.98% H, 17.37% N, 9.83% S; FTIR: 3441.6
(NH), 3021.8 (CH), 1620.6 (C=N); 1H-NMR: 12.30 (1H, s, NH), 8.83 (1H, s, NH), 8.30-7.49 (9H,
m, ArH), 6.19-6.06 (1H, m, CH=CH2), 5.47 (1H, d, CH=CH2) (JA,B= 17.2 Hz), 5.38 (1H, d,
CH=CH2) (JA,B= 9.9 Hz), 4.49 (2H, m, HNCH2); 13C-NMR: 180.16 (C=S), 158.65 (Cq), 156.04
(Cq), 151.53 (Cq), 137.27 (Cq), 134.61 (CHAr), 132.73(1H, m, CH=CH2), 131.21 (CHAr), 129.85
(CHAr), 128.90 (CHAr), 128.42 (CHAr), 127.83 (CHAr), 120.63 (CHAr),118.98 (1H, m, CH=CH2),
112.59 (Cq), 49.16 (NCH2).
1-Isobutyl-3-(2-phenylquinazolin-4-yl) thiourea (7d).
(NH2R= isobutylamine); Yield: 0.14 g (19%); M.p. 150-151oC; Calc.for C19H20N4S (336.45):
67.83% C, 5.99% H, 16.65% N, 9.53% S; found: 67.75% C, 5.92% H, 16.59% N, 9.52% S; FTIR:
1
3427.65 (NH), 2957.7, 2918.7 (CH), 1620.29 (C=N); H-NMR: 12.26 (1H, s, NH), 8.95 (1H, s,
NH), 8.41-7.61 (9H, m, ArH), 3.78 (2H, t, NHCH2) (JA,B= 6.57 Hz), 2.32-2.25 (1H, m, CH(CH3)2),
1.18 (6H, d, CH(CH3)2) (JA,B= 6.57 Hz); 13C-NMR: 180.18 (C=S), 158.83 (Cq), 156.12 (Cq), 151.41
(Cq), 137.52 (Cq), 134.57 (CHAr), 131.18 (CHAr), 129.75 (CHAr), 128.83 (CHAr), 128.31 (CHAr),
127.80 (CHAr), 120.68 (CHAr), 112.60 (Cq), 54.38 (NHCH2), 28.16 (NCH2CH), 20.75 (CH3).
1-Cyclohexyl-3-(2-phenylquinazolin-4-yl) thiourea (7e).
(NH2R= cyclohexylamine); Yield: 0.25 g (30%); M.p. 154-155oC; Calc.for C21H22N4S (362.49):
69.58% C, 6.12% H, 15.46% N, 8.84% S; Found: 69.41% C, 6.12% H, 15.38% N, 8.74% S; FTIR:
3441.7, 3425.8 (NH), 1619.3 (C=N); 1H-NMR: 12.08 (1H, b, NHCH), 8.75 (1H, s, NH), 8.32-7.54
(9H, m, ArH), 4.28-4.38 (1H, m, NHCH), 2.34-2.27 (2H, m, CH2), 1.91-1.71 (4H, m, 2CH2), 1.55-
13
1.38 (4H, m, 2CH2); C-NMR: 178.54 (C=S), 158.90 (Cq), 156.07 (Cq), 151.45 (Cq), 137.69 (Cq),
134.55 (CHAr), 131.15 (CHAr), 129.77 (CHAr), 128.92 (CHAr), 128.40 (CHAr), 127.80 (CHAr),
120.65 (CHAr), 112.66 (Cq), 55.49 (CH), 32.78 (CH2), 32.78 (CH2), 25.87 (CH2), 25.17 (CH2).
1-Phenyl-3-(2-phenylquinazolin-4-yl)thiourea (7f).
(NH2R= aniline); Yield: 0.35 g (43%); M.p. 165-166oC; Calc.for C21H16N4S (356.44): 70.76% C,
4.52% H, 15.72% N, 8.99% S; Found: 70.58% C, 4.52% H, 15.64% N, 8.83% S; FTIR:

1
3436.3, 3418.7 (NH), 1617.3 (C=N); H-NMR: 14.26 (1H, s, NHPh), 8.93 (1H, s, NH), 8.35-7.29
(14H, m, ArH); 13C-NMR: 178.62 (C=S), 158.57 (Cq), 155.96 (Cq), 151.64 (Cq), 144.85(Cq),
138.49 (Cq), 137.36 (Cq), 134.85 (CHAr), 131.31 (CHAr), 129.93 (CHAr), 129.24 (CHAr), 128.39
(CHAr), 128.03 (CHAr), 126.88 (CHAr), 124.13 (CHAr), 120.65 (CHAr), 112.62 (Cq); MS, m/z (Ir/%):
356 (6), 323 (7), 276 (9), 264 (12), 263 (51), 222 (13), 221 (100), 205 (95), 178 (8), 135 (49), 118
(17), 104 (7), 102 (20), 93 (21), 91 (6), 77 (57), 51 (25).
1-(4-Methylphenyl)-3-(2-phenylquinazolin-4-yl) thiourea (7g).
(NH2R= p-toluidine); Yield: 0.31 g (38%); M.p. 179-180oC; Calc. for C22H18N4S (370.47): 71.33%
C, 4.90% H, 15.12% N, 8.65% S; Found: 71.21% C, 4.89% H, 15.11% N, 8.62% S; FTIR: 3422.5
1
(NH), 1619.9(C=N); H-NMR: 14.16 (1H, s, NHPh), 8.92 (1H, s, NH), 8.36-7.29 (13H, m, ArH),
13
2.40 (3H, s, CH3); C-NMR: 178.62 (C=S), 158.57 (Cq), 155.99 (Cq), 151.52 (Cq), 144.85 (Cq),
138.49 (Cq), 137.30 (Cq), 136.83 (Cq), 134.84 (CHAr), 131.32 (CHAr), 129.82 (CHAr), 129.09
(CHAr), 128.38 (CHAr), 128.03 (CHAr), 124.18 (CHAr), 120.67 (CHAr), 112.63 (Cq), 21.33 (CH3);
MS, m/z (Ir/%): 337 (4), 264 (18), 263 (62), 222 (33), 221 (85), 206 (19), 205 (100), 149 (54), 148
(18), 118 (15), 107 (71), 106 (58), 91 (29), 77 (29).
1-(3-Methylphenyl)-3-(2-phenylquinazolin-4-yl) thiourea (7h).
(NH2R= m-toluidine); Yield: 0.36 g (43%); M.p. 157-158oC; Calc. for C22H18N4S (370.47):
71.33% C, 4.90% H, 15.12% N, 8.65% S; Found: 71.32% C, 4.90% H, 15.10% N, 8.65% S; FTIR:
3405.2 (NH), 1618.7 (C=N); 1H-NMR: 14.22 (1H, s, NHPh), 8.91 (1H, s, NH), 8.38-7.11 (13H, m,
ArH), 2.41 (3H, s, CH3); 13C-NMR: 178.53 (C=S), 158.56 (Cq), 155.84 (Cq), 151.38 (Cq),
144.76(Cq), 138.49 (Cq), 137.30 (Cq), 136.83 (Cq), 134.86 (CHAr), 131.37 (CHAr), 129.87 (CHAr),
129.06 (CHAr), 128.46 (CHAr), 128.05 (CHAr), 127.66 (CHAr), 124.64 (CHAr), 121.07 (CHAr),
120.67 (CHAr), 112.63 (Cq), 21.69 (CH3).
1-(2-Methylphenyl)-3-(2-phenylquinazolin-4-yl) thiourea (7I).
(NH2R= o-toluidine); Yield: 0.42 g (51%); M.p. 157-158oC; Calc. for C22H18N4S (370.47): 71.33%
C, 4.90% H, 15.12% N, 8.65% S; Found: 71.03% C, 4.64% H, 14.92% N, 8.41% S; FTIR: 3325.2
(NH), 1623.59 (C=N); 1H-NMR: 14.22 (1H, s, NHPh), 8.91 (1H, s, NH), 8.38-7.11 (13H, m, ArH),
2.41 (3H, s, CH3); 13C-NMR: 178.53 (C=S), 158.56 (Cq), 155.84 (Cq), 151.38 (Cq), 144.76(Cq),
138.49 (Cq), 137.30 (Cq), 136.83 (Cq), 134.86 (CHAr), 131.37 (CHAr), 129.87 (CHAr), 129.06
(CHAr), 128.46 (CHAr), 128.05 (CHAr), 127.66 (CHAr), 124.64 (CHAr), 121.07 (CHAr), 120.67
(CHAr), 112.63 (Cq), 21.69 (CH3).

599
Molecules 2001, 6
1-(4-Methoxyphenyl)-3-(2-phenylquinazolin-4-yl) thiourea (7j).
(NH2R= p-anisidine); Yield: 0.34 g (40%); M.p. 168-169oC; Calc. for C22H18N4OS (386.47):
68.37% C, 4.69% H, 14.50% N, 8.30% S; Found: 68.24% C, 4.57% H, 14.49% N, 8.23% S; FTIR:
3428.2 (NH), 2934.9 (CH), 1616.8 (C=N); 1H-NMR: 14.09 (1H, s, NHPh), 8.91 (1H, s, NH), 8.35-
6.98 (13H, m, ArH), 3.86 (3H, s, OCH3); 13C-NMR: 178.78 (C=S), 158.39 (Cq), 155.98 (Cq),
152.49 (Cq), 151.55 (Cq), 141.78 (Cq), 137.32 (Cq), 134.86 (CHAr), 131.4(Cq), 131.32 (CHAr),
129.87 (CHAr), 129.09 (CHAr), 128.35 (CHAr), 128.03 (CHAr), 125.78 (CHAr), 120.67 (CHAr),
114.48 (CHAr), 113.45 (Cq), 112.63 (Cq), 55.75 (OCH3).
1-(4-nitrophenyl)-3-(2-phenylquinazolin-4-yl) thiourea (7k).
(NH2R= p-nitroaniline); Yield: 0.48 g (53%); M.p. 165-166oC; Calc. for C21H15N5O2S (401.44):
62.83% C, 3.77% H, 17.45% N, 7.99% S; Found: 62.66% C, 3.58% H, 17.24% N, 7.84% S; FTIR:
1
13
3333.0 (NH), 1615.7 (C=N); H-NMR (CF3COOD): 8.87-7.94 (13H, m, ArH); C-NMR: 179.93
(C=S), 161.56 (Cq), 160.34 (Cq), 147.97 (Cq), 145.71 (Cq), 142.34 (Cq), 142.01 (CHAr), 138.41
(CHAr), 133.84 (CHAr), 132.67 (CHAr), 131.27 (Cq), 130.90 (CHAr), 127.36 (CHAr), 126.21 (CHAr),
125.73 (CHAr), 122.65 (CHAr), 114.20 (Cq).
1-(3-nitrophenyl)-3-(2-phenylquinazolin-4-yl)thiourea (7l).
(NH2R= m-nitroaniline); Yield: 0.39 g (41%); M.p. 174-175oC; Calc. for C21H15N5O2S (401.44):
62.83% C, 3.77% H, 17.45% N, 7.99% S; Found: 62.74% C, 3.64% H, 17.32% N, 7.87% S; FTIR:
1
13
3315.6 (NH), 1620.8 (C=N); H-NMR (CF3COOD): 8.87-7.75 (13H, m, ArH); C-NMR: 180.60
(C=S), 161.55 (Cq), 160.60 (Cq), 150.54 (Cq), 142.41 (Cq), 142.34 (Cq), 142.07 (CHAr), 140.60 (Cq),
138.47 (CHAr), 133.90 (CHAr), 132.91 (CHAr), 132.82 (CHAr), 132.76 (CHAr), 131.27 (Cq), 130.97
(CHAr), 125.91 (CHAr), 124.93 (CHAr), 122.71 (CHAr), 121.58(CHAr), 114.30 (Cq).
1-(4-Chlorophenyl)-3-(2-phenylquinazolin-4-yl) thiourea (7m).
(NH2R= p-chloroaniline); yield: 048 g (55%); M.p. 187-188oC; Calc.for C21H15ClN4S (390.89):
64.53% C, 3.87% H, 9.07% Cl, 14.33% N, 8.20% S; found: 64.34% C, 3.69% H, 9.01% Cl,
1
14.21% N, 8.16% S;; FTIR: 3430.3, 3339.3 (NH), 1620.40 (C=N); H-NMR (CF3COOD): 8.74-
7.48 (13H, m, ArH); 13C-NMR: 180.40 (C=S), 161.44 (Cq), 160.73 (Cq), 142.28 (Cq), 141.98
(CHAr), 138.41 (CHAr), 137.24 (Cq), 136.92 (Cq), 133.80 (CHAr), 132.63 (CHAr), 131.07 (Cq),
130.88(CHAr), 127.84 (CHAr), 125.86 (CHAr), 122.58 (CHAr), 114.27 (Cq).

600
Molecules 2001, 6
1-(1-Naphthyl)-3-(2-phenylquinazolin-4-yl) thiourea (7n).
(NH2R= 1-naphthylamine); Yield: 0.41 g (45%); M.p. 168-169oC; Calc. for C25H18N4S (406.50):
73.87% C, 4.46% H, 13.78% N, 7.89% S; Found: 73.83% C, 4.46% H, 13.77% N, 7.84% S; FTIR:
1
3250.1 (NH), 3055.0, 2943.4 (CH), 1619.4 (C=N); H-NMR: 14.27 (1H, s, NHPh), 9.16 (1H, s,
13
NH), 8.28-7.29 (19H, m, ArH); C-NMR: 180.79 (C=S), 164.76 (Cq), 158.76 (Cq), 156.24 (Cq),
151.73 (Cq), 141.70 (Cq), 137.02 (Cq), 134.90 (CHAr), 134.61(Cq), 131.19 (CHAr), 129.97 (CHAr),
129.02 (CHAr), 128.87 (CHAr), 128.55 (CHAr), 128.24 (CHAr), 128.05 (CHAr), 127.16 (CHAr),
126.64 (CHAr), 125.65 (CHAr), 124.71 (CHAr), 122.41 (CHAr), 120.19 (CHAr), 112.74 (Cq).
1-(2-Naphthyl)-3-(2-phenylquinazolin-4-yl) thiourea (7o).
(NH2R= 2-naphthylamine); Yield: 0.55 g (66%); M.p. 179-180oC; Calc. for C25H18N4S (406.50):
73.87% C, 4.46% H, 13.78% N, 7.89% S; Found: 73.74% C, 4.38% H, 13.61% N, 7.80% S; FTIR,
-1
1
~
ν /cm : 3429.1, 3374.2 (NH), 3057.6 (CH), 1618.4 (C=N); H-NMR (CF3COOD): 8.72-7.63
(19H, m, ArH); 13C-NMR (CF3COOD): 179.30 (C=S), 161.29 (Cq), 160.30 (Cq), 142.09 (Cq),
141.83 (CHAr), 138.41 (CHAr) 136.08 (Cq), 135.59 (Cq), 135.02 (Cq) , 133.68 (CHAr), 132.59
(CHAr), 131.86 (CHAr), 131.05 (Cq), 130.99 (CHAr), 130.67 (CHAr), 129.89 (CHAr), 129.63 (CHAr),
126.46 (CHAr), 125.68 (CHAr), 124.82 (CHAr), 122.41 (CHAr), 114.07 (Cq).
1-(2-phenylquinazolin-4-yl)-3-(2-pyridyl) thiourea (7p).
(NH2R= 2-aminopyridine); Yield 0.33 g (41%); M.p. 207-208oC; Calc.for C20H15N5S (357.43):
67.21% C, 4.23% H, 19.59% N, 8.97% S; Found: 67.04% C, 3.97% H, 19.22% N, 8.83% S; FTIR,
-1
1
~
ν /cm : 3348.7 (NH), 3059.4 (CH), 1621.7 (C=N); H-NMR (DMSO-d6): 8.71-7.27 (13H, m,
ArH); 13C-NMR: 179.57 (C=S), 161.05 (Cq), 155.96 (Cq), 151.64 (Cq), 144.85(Cq), 138.49 (Cq),
135.90 (Cq), 137.73 (CHAr), 134.08 (CHAr), 130.36 (CHAr), 127.98 (CHAr), 127.69 (CHAr), 126.76
(CHAr), 123.26 (CHAr), 119.93 (CHAr), 114.25 (Cq); MS, m/z (Ir/%): 357 (14), 324 (7), 264 (30),
263 (49), 222 (21), 221 (100), 205 (82), 178 (8), 136 (55), 118 (28), 104 (13), 102 (29), 94 (27), 78
(56), 77 (38), 51 (27).
1-(1-Adamantyl)-3-(2-phenylquinazolin-4-yl) thiourea (7q).
(NH2R= 1-adamantanamine hydrochloride); Yield: 0.29g (31%); M.p. 202-203oC; Calc.for
C25H26N4S (414.50): 72.43% C, 6.32% H, 13.52% N, 7.73% S; Found: 72.31% C, 6.27% H,
-1
1
~
13.41% N, 7.54% S; FTIR, ν /cm : 3445.3 (NH), 2909.9 (CH), 2854.9 (CH), 1622.5 (C=N); H-
NMR: 11.77 (1H, s, NH), 8.53 (1H, s, NH), 8.27-7.43 (9H, m, ArH), 2.53-2.41 (6H, m, 3CH2),
13
2.26-2.09 (6H, m, 3CH2), 1.84-1.68 (3H, m, 3CH); C-NMR: 177.48 (C=S), 156.07 (Cq), 149.83
(Cq), 137.91 (Cq), 134.63 (CHAr), 131.02 (CHAr), 129.81 (CHAr), 128.70 (CHAr), 127.68 (CHAr),
120.67 (CHAr), 112.75 (Cq), 55.91 (NHCAd), 41.10 (CH2), 36.67 (CH2), 29.97 (CH); MS, m/z

601
Molecules 2001, 6
(Ir/%): 414.2 (4), 380.3 (2), 264 (7), 263 (21), 222 (32), 221 (75), 205 (65), 193 (15), 151 (16), 135
(100), 118 (17), 94 (45), 77 (29).
1-(3-Homoadamantyl)-3-(2-phenylquinazolin-4-yl) thiourea (7r).
o
(NH2R= 3-homoadamantanamine hydrochloride); Yield: 0.3 g (33%); M.p. 217-218 C; Calc.for
C26H28N4S (428.59): 72.86% C, 6.58% H, 13.07% N, 7.48% S; Found: 72.43% C, 6.48% H,
-1
1
~
13.01% N, 7.24% S; FTIR, ν /cm : 3436.2 (NH), 2909.9 (CH), 2849.9 (CH), 1620.4 (C=N); H-
NMR: 11.98 (1H, s, NH), 8.64 (1H, s, NH), 8.36-7.54 (9H, m, ArH), 2.61-1.53 (15H, m, Ad); 13C-
NMR: 176.92 (C=S), 159.19 (Cq), 156.03 (Cq), 151.30 (Cq), 137.86 (Cq), 134.45 (CHAr), 131.03
(CHAr), 129.71 (CHAr), 128.71 (CHAr), 127.72 (CHAr), 120.73 (CHAr), 112.65 (Cq), 60.98 (CH2),
43.15 (CH2), 37.84 (CH2), 35.56 (CH2), 31.22 (CH), 31.18 (CH2), 27.82 (CH); MS, m/z (Ir/%):
428.2 (3), 264 (12), 263 (34), 222 (48), 221 (86), 205 (83), 165 (12), 149 (100), 118 (13), 94 (23),
77 (29).
1-(1-Adamantylmethyl)-3-(2-phenylquinazolin-4-yl) thiourea (7s).
[NH2R= 1-(1-adamantylmethylamine hydrochloride)]; Yield: 0.33 g (34%); M.p. 197-198 oC; Calc.
for C26H28N4S (428.53): 72.86% C, 6.59% H, 13.07% N, 7.48% S; Found: 72.86% C, 6.57% H,
-1
1
~
13.04% N, 7.39% S; FTIR, ν /cm : 3450.3 (NH), 2909.9 (CH), 2849.5 (CH), 1620.0 (C=N); H-
NMR: 12.04 (1H, s, NH), 8.90 (1H, s, NH), 8.31-7.51 (9H, m, ArH), 3.69 (2H, d, NHCH2) (JA,B
=
6.14 Hz), 1.96-1.56 (15H, m, Ad); 13C-NMR: 180.75 (C=S), 156.08 (Cq), 151.43 (Cq), 138.70 (Cq),
137.76 (Cq), 134.63 (CHAr), 131.04 (CHAr), 129.78 (CHAr), 128.78 (CHAr), 127.85 (CHAr), 120.77
(CHAr), 112.67 (Cq), 58.74 (NHCH2), 40.85 (CH2 Ad), 36.95 (CH2 Ad), 34.82 (CqAd), 28.38 (CH);
MS, m/z (Ir/%): 428 (9), 395 (5), 264 (15), 263 (24), 222 (41), 221 (49), 205 (64), 165 (11), 149
(12), 135 (100), 118 (9), 93 (19), 77 (23).
References and Notes
1. Fathalla, W.; Čajan, M. and Pazdera, P., Molecules, 2001, 6, 557-573.
2. Fathalla, W.; Čajan, M. and Pazdera, P., Molecules, 2000, 5, 1210-1223.
3. Fathalla, W., Marek, J. and Pazdera, P., Molecules, 2001, 6, 574-587.
4. Bodajla, M.; Stankovský, Š.; Špirková, K.: Collect. Czech. Chem. Commun., 1995, 60, 1415.
5. Bodajla, M.; Stankovský, Š.; Špirková, K.; Jantová, S.: Collect. Czech. Chem.
Commun., 1996, 61, 1681.
6. Bodajla, M.; Stankovský, Š.; Jantová, S.; Hudecová, D.; Špirková, K.: Chem.
Papers, 1996, 50, 28.
7. Pazdera, P.; Nováček, E.; Kalviňš, I.; Trapencieris, P.; Pugovics, O.: Chem. Papers, 1991, 45,
527.
8. Pazdera, P.; Ondráček, D.; Nováček, E.: Chem. Papers, 1989, 43(6), 771.

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Molecules 2001, 6
9. The complete computational analysis of all the predicted structures and the X-ray analysis data
for compounds 7a and 7b are available from the authors.
10. Sheldrick, G. M.: Acta Crystallogr., Sect. A.: Fundam. Crystallogr., 1990, 46, 467.
11. Sheldrick, G. M.: SHELXL93: Program for Structure Refinement. University of Göttingen,
Göttingen, 1993.
Sample Availability: Available from the authors.
© 2001 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.