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

Article abstract of DOI:10.3390/60700574

1,1-Disubstituted-3-(2-phenyl-3H-quinazolin-4-ylidene)thioureas (8) were synthesized in a one pot reaction of N-(2-cyanophenyl)benzimidoyl isothicyanate (3) with secondary amines. The products underwent transamination reactions. Compounds 8a-8g were identified by FTIR, ¹H-NMR, ¹³C-NMR, mass spectroscopy and X-ray crystallography.

Full text of DOI:10.3390/60700574

Molecules 2001, 6, 574-587
molecules
ISSN 1420-3049
http://www.mdpi.org
One-Pot Quinazolin-4-ylidenethiourea Synthesis via N-(2-
Cyanophenyl)benzimidoyl isothiocyanate
Walid M. Fathalla.1, Michal Čajan1,2, Jaromír Marek3 and Pavel Pazdera1,*
1 Department of Organic Chemistry, Faculty of Science, Masaryk University, Brno, Czech Republic,
Tel.: +420 5 41129305, Fax: +420 5 41211214.
2 National Center for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech
Republic.
3
Department of Inorganic Chemistry, Masaryk University, 611 37 Brno, The 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: 1,1-Disubstituted-3-(2-phenyl-3H-quinazolin-4-ylidene)thioureas (8) were
synthesized in a one pot reaction of N-(2-cyanophenyl)benzimidoyl isothicyanate (3) with
secondary amines. The products underwent transamination reactions. Compounds 8a-8g
were identified by FTIR, 1H-NMR, 13C-NMR, mass spectroscopy and X-ray
crystallography.
Keywords: N-(2-cyanophenyl)benzimidoyl isothicyanate, 1,1-disubstituted-3-(2-phenyl-
3H-quinazolin-4-ylidene)thioureas, intramolecular cycloaddition, 1,1-disubstituted-3-[(2-
cyanophenylimino)phenylmethyl]thioureas, quinazolines.
Introduction
The benzodiazocines [1] and quinazolines [2,3] represent two classes of heterocyclic compounds
with diverse physiological activities, e.g., acting as central nervous system depressants and calcium
sensitizing agents. Several quinazoline derivatives have been tested for their biological and
pharmacological activities. These derivatives posses hypnotic [4], diuretic [5], antihistaminic [6], anti-

Molecules 2001, 6
575
inflammatory [7], bronchodilator [8], antihypertensive [9], antituberculousis [10], antimicrobial [11],
anticonvulsant [12], sedative [12] and hypoglycemic activities [13].
These derivatives are intermediates for various pharmaceutical agents. Consequently, numerous
research groups have attempted to synthesize these compounds. Others have modified their basic
structures by changing the size of the rings or by changing the heteroatoms. Stankovsky’s group [14-
16] has described the synthesis of 2,4-disubstituted-6H-5,1,3-benzothiadiazocines by the
intramolecular substitution reaction of the 1,1-di-R-3-[2-(chloromethylphenylimino}phenylmethyl]
thioureas.
Results and Discussion
We describe in this paper the intramolecular cycloaddition reactions of the products formed in situ
by addition of secondary amines to N-(2-cyanophenyl)benzimidoyl isothicyanate (3). The very reactive
starting compound 3 was easily prepared from N-(2-cyanophenyl)benzamide (1). The amide 1 was
transformed by the action of phosphorous pentachloride into the benzimidoyl chloride 2 that
subsequently reacts with potassium thiocyanate to give the desired isothiocyanate derivative 3. The
proposed structure of compound 3 is supported by its IR spectrum that showed the presence of the
expected isothiocyanato and cyano moieties. The isothiocyanate 3 reacts with secondary amines
(morpholine, piperidine, pyrrolidine, N-methylpiperazine, and diphenylamine) to give the cyclic
products.
The proposed structures of the cyclisation products can be explained by considering the in situ
formation of the thiourea derivatives 4a-4d, 4f (Scheme 1). This fact was confirmed by the isolation
and identification of the thiourea derivative 4e obtained when 3 was reacted with dibutylamine. This
reaction required basic conditions to accelerate the cyclisation reaction. The intermediates 4a-4f
contain two active nucleophilic sites in the molecule, which compete in the attack of the nitrile group
and finally give the cyclic product. The reactive sites are the sulfur and nitrogen atoms present in the
thioamide group of the thiourea derivatives 4a-4f. The intramolecular reaction would give one or both
cyclic products generally: The benzothiadiazocine derivatives 5 via sulfur attack [4-6], or the
quinazoline derivatives 6 via nitrogen attack. The reaction could be extended to involve the Dimorth
rearrangement products 7 or their tautomers 8.
The intramolecular addition reactions of thioureido derivatives containing functionalized carboxy
groups under neutral and basic conditions take part on the nitrogen atom [17,18]. Consequently the
expected products formed were the quinazoline derivatives 6 giving the more thermodynamically
stable six membered rings. The resultant quinazoline derivatives 6 undergo Dimroth rearrangement by
the effect of the excess amine to give 7, which were converted spontaneously to finally give the
thiourea derivatives 8.

Molecules 2001, 6
576
C
N
N
C
N
a
Cl
O
NH
2
1
b
S
C
C
N
NH
S
C
N
c
R
R
C
N
N
N
N
3
4a-4f
d
d,e
S
C
HN
R
NH
R
S
N
d,e
N
R
N
R
N
N
N
6a-6f
5a-5f
NR2: 6a morpholine 6d
N-methylpiperazine
diphenylamine
6b piperidine 4e, 6e dibutylamine
6c pyrrolidine 6f
a: PCl5, toluene, 110°C, 8 h; b: KSCN, acetone, -5°C, 2h; c: NHR2, acetone, 25°C, 24 h;
d: CHCl3, N(C2H5)3, 50°C, 4h; e: DMF, reflux, 24h, or MeOH, MeONa, reflux, 24h.
Scheme 1. Synthesis of the quinazoline derivatives 6 and alternative reaction pathways.

Molecules 2001, 6
577
R
R
N
S
C
H
NH
N
N
S
R
N
N
N
R
N
7a-7f
6a-6f
R
R
N
N
S
H
N
N
8a-8f
NR2: 8a morpholine
8b piperidine
8d
8e
8f
N-methylpiperazine
dibutylamine
diphenylamine
8c pyrrolidine
Scheme 2. The spontaneous conversion of compounds 6 to the quinazoline derivatives 8.
The identities of the synthesized 3, 4, and 8 were supported by the spectral data as follows: the
infrared spectra show the disappearance of ν(NCS) and ν(CN) bands present in case of the
isothiocyanate 3 and the existence of ν(NH) and ν(C=N) bands at 3220 cm-1, and 1613 cm-1,
respectively, for the cyclic forms 8a-8f. The infrared spectra also gave two pieces of evidence in the
case of the formation of the open chain thiourea derivative 4e: the first was the ν(CN) band at 2228
cm-1 and the second the ν(NH) band at 3210 cm-1 together with the absence of ν(C=N) band of the
quinazoline derivative at 1613 cm-1.
The proton nuclear magnetic resonance spectra show the introduction of the CH2 groups from the
amino group when reacting with isothiocyanate 3. It was a surprise to find that the two CH2 groups
adjacent to the nitrogen atom of the amines are identical in all cases except for the case of pyrrolidine
which gave two distinct peaks with chemical shifts of ca 4.01 and ca 3.87 ppm, respectively. This
feature can be readily explained if we examine the geometry of 8 (Figure 2, 3).

Molecules 2001, 6
578
1
The H-NMR spectra gave no clear evidence supporting the formation of the open chain
intermediate in case of 4e. The important evidence for the formation of the quinazolines 8 is the
chemical shift at ca 16.73 ppm due to the NH group. The high chemical shift is attributed to high
interactions between the thiocarbonyl group and the NH of the quinazoline ring. The alternative
formation of 7 would have the NH signal at a lower chemical shift (ca 12 ppm) according to the
simulated NMR spectra.
The most important peak shown by the 13C-NMR is the peak corresponding to C=S with a
chemical shift of ca 183-184 ppm, which plays an important role in the structure identification of the
cyclic products. Of coarse, it is associated with the quinazoline structures 6-8 not the thiadiazocines
5a-5f. 13C-NMR spectra gave two different peaks corresponding to the -CH2- group of the amines
8a-8e although we expected to observe only one peak. This is obviously due to the geometry of the
product, in which one -NCH2- group from the amine (this group has almost the same chemical
environment with respect to the other -NCH2- group) is affected by anisotropy of the C=S group. This
fact is maximized in the 1H-NMR spectrum when using pyrrolidine as an amine. It is apparent that the
two CH2 groups adjacent to the nitrogen atom in the compound 8e are not identical (51.60 ppm, 51.27
ppm) and the other two neighboring NCH2CH2 (30.83 ppm, 28.90 ppm) groups are not equivalent
13
due to the same mentioned reason. The C-NMR spectrum of thiourea 4e show that the C=S group
appeared at 178 ppm and the nitrile group at 107 ppm.
The mass spectra gave the molecular ion for all the products 8a-8d, next it gave molecular
fragment which corresponds to the thioamide moiety at m/z 131 (morpholine), 128 (piperidine), 114
(pyrrolidine), and 142 (N-methylpiperazine) and the molecular fragment at 221 corresponding to the
residue of the compound (2-phenyl-4-quinazoilinimine moiety). The products of fragmentation are
shown on Figure 1.
R
R
R
R
R
R
N
N
N
N
N
N
N
N
S
H
N
S
S
H
H
N
N
N
205
265
221
Figure 1. Mass spectral fragmentations in compounds 8
A single crystal of pyrrolidine-1-carbothioic acid (2-phenyl-3H-quinazolin-4-ylidene) amide (8c)
was used for X-ray structure analysis. The structural data obtained are presented in Tables 1-3 and
correspond to a great extent with those calculated by ab initio HF/6-31G** method. The calculated and
the X-ray molecular structures of 8c are presented in Figures 2 and 3. The analysis shows that the

Molecules 2001, 6
579
structure formed is the tautomeric form 8 of the Dimroth rearrangement product 7. The reason for this
could be explained if we examine the structures of all possible products 5-8 and the structures reported
by Stankovsky [14-16], [19].
The ab initio studies together with the X-ray analysis show that the compound 8c is almost planar
with the phenyl ring at position 2 slightly out of plane and the pyrrolidine methylene groups out of
plane. The electrons in π-orbitals are in good conjugation as presented in Figure 3. The hydrogen bond
interactions between the thiocarbonyl group and the NH of the quinazoline ring add extra stability to
the isolated product (Scheme 2). These hydrogen bond interactions were identified from the X-ray
analysis and the computational studies, which show a bond distance of about 2.17 Å and 2.18 Å,
respectively.
The intermediary thiourea derivatives 6 have the quinazoline moiety in one plane while the phenyl
group, thioamide moiety and the pyrrolidine are each in a different plane. The same results were
obtained for above mentioned benzothiadiazocine 5. The calculated (HF/6-31G** method) energy
difference between 6 and 8 is 30.69 kcal.mol-1, while the energy difference between 5 and 6 is 36.61
kcal.mol-1. This shows that the more stable compound is the isolated quinazoline derivative 8.
The 6-methylene analogues of 5 reported in the literature [14-16] have the benzene ring and the N1
together with the CH2 group in one plane, while the [phenyl-C2-N3-C4-S5-NR] is in another plane,
indicating that the electrons in the π-orbitals are in good conjugation.
Figure 2. X-ray analysis of compound 8c.

Molecules 2001, 6
580
Figure 3. Molecular design of 8c according to HF/6-31G** method.
Table 1. Selected interatomic distances in 8c.
Bond Length [Å]
Bond
Bond Length [Å]
X-ray HF/6-31G**
Bond
X-ray
HF/6-31G**
N1-C2
N1-C10
C2-N3
C2-C19
N3-C4
C4-N11
N11-C12
1.30
1.39
1.38
1.49
1.36
1.32
1.37
1.27
1.38
1.37
1.49
1.35
1.30
1.36
C12-N13
C12-S18
N13-C14
N13-C17
C14-C15
C15-C16
C16-C17
1.34
1.72
1.48
1.47
1.52
1.52
1.52
1.33
1.71
1.47
1.47
1.52
1.52
1.52
Table 2. The most important bond angles in 8c.
Angle [°]
Angle [°]
X-ray
HF/6-31G**
X-ray
HF/6-31G**
N1-C2-C19
C2-N1-C10
N1-C2-N3
119.80
117.34
123.17
123.63
125.66
111.85
119.05
125.13
103.49
120.14
117.99
122.99
124.19
126.65
112.38
119.49
124.17
103.46
C14-N13C17
N13-C17-C16
N1-C10-C5
C10-C5-C6
C5-C6-C7
111.84
103.17
122.81
120.25
119.86
119.88
120.82
122.91
121.32
112.15
103.47
122.56
120.07
120.10
119.80
120.79
122.15
120.53
C2-N3-C4
N3-C4-N11
N11-C12-N13
N13-C12-S18
C12-N13-C17
N13-C14-C15
C6-C7-C8
C7-C8-C9
C2-C19-C24
C2-N3-H3

Molecules 2001, 6
Torsion angle [°]
581
Table 3. The most important torsion angles in 8c.
Torsion angle [°]
X-ray
HF/6-31G**
X-ray
HF/6-31G**
C14-N13-C17-C16
C17-N13-C14-C15
C16-C17-N13-C12
C17-N13-C12-S18
C17-N13-C12-C11
S18-C12-N11-C4
15.73
12.06
N11-C4-N3-C2
C4-N3-C2-N1
N3-C2-N1-C10
C2-N1-C10-C5
C12-N11-C4-N3
N1-C2-N3-H3
-178.35
-0.56
0.93
-0.63
2.05
179.60
-178.96
-1.43
023
6.92
11.68
-163.11
-1.31
178.84
7.02
-168.09
-2.84
176.89
-3.05
0.92
-0.44
175.29
The predicted structure contains a thioamide group, so we can confirm the structure chemically
through a transamination reaction of compound 8a by N-methylpiperazine to give 8d (Scheme 4).
CH3
N
O
N
N
N
N
S
H
N
S
H
f
N
N
N
8d
e,g
8a
NH
S
O
N
N
N
6a
e: DMF, reflux, 24h, or MeOH, MeONa, reflux, 24h.
f: HNR2, DMF, reflux, 2-4h; g: Conc. H2SO4, 2 d.
Scheme 4. Transamination reaction for compound 8a.

Molecules 2001, 6
582
The Dimroth rearrangement reaction might take place upon refluxing the expected quinazoline
derivatives 6a-6f in DMF or in MeOH / MeONa for a long period, but no such reactions were detected,
providing further support for the formation of the quinazolin-4-ylidenthioureas 8. A retro-Dimroth
rearrangement reaction to give 6a might be expected to take place when 8a was left standing for 2 days
in conc. sulfuric acid but formation of this product was not detected. We confirmed the structures of
the 1,1-disubstituted-3-(2-phenyl-3,H-quinazolin-4-ylidene) thiourea compounds 8a-8f on the basis of
the above spectral data, by comparison of this data with the computer simulated spectra and from
knowledge about the chemistry of the thiourea derivatives [17,18].
Conclusions
3-[(2-cyanophenyl-imino)-phenylmethyl]-1,1-disubstituted thioureas undergo a regioselective
intramolecular cycloaddition reaction to give intermediate 1,1-disubstituted-4-imino-2-phenyl-4H-
quinazolin-3-carbothioic acid amides (6) that are converted spontaneously into 1,1-disubstituted-3-(2-
phenyl-3,H-quinazolin-4-ylidene)thioureas 8. These products undergo transamination reactions.
Acknowledgments
This work was supported by the grants of the Ministry of Education of the Czech Republic (Grant
No. CEZ: J07/98: 143100011) and Grant Agency of the Czech Republic (Grant No. 203/01/1333). We
would like to thank analytical department of Lachema Co., Brno, Czech Republic for elemental
analysis. The authors thank the Czech Academic Supercomputer Center in Brno for providing the
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). The
eluent used was a 20:80 mixture of acetone-benzene. TLC detection was accomplished with a Fluotes
universal instrument (Quarzlampen, Hanau) and iodine vapors. The purity of compounds 4 and 8 were
proven by their elemental analysis, measured on an Erba 1102 instrument. FTIR spectra (reported as
-1
~
ν /cm ) were taken on a Genesis (Unicam) spectrometer in potassium bromide pellets. NMR spectra
1
were measured on a Bruker Avance DRX-500 spectrometer. Unless stated otherwise H, 13C-NMR
spectra were measured in CDCl3 solutions and tetramethylsilane was used as the internal standard.
13
1
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 Development, Inc., Toronto, Canada).
The X-ray structural data of compound 8c (Table 4) were collected with a KUMA KM-4 kappa four-
circle diffractometer. The structure was solved by direct methods using SHELXS86 [20] and refined
on F2 for all reflections using SHELXl93 [21]. Crystals suitable for X-ray determination were obtained

Molecules 2001, 6
583
as white prisms by crystallization from CHCl3 - petroleum ether at room temperature. The
crystallographic data for 8c have been deposited with the Cambridge Crystallographic Data Center as
supplementary publication number CCDC 143663. Geometry optimization of structure 8c was
performed at ab initio level of quantum chemical calculation by HF/6-31G**. Mass spectrometry was
determined (electron impact, 70 eV) with a Fisons TRIO 1000 and GC 8000 series instrument.
Table 4. Crystal data and structure refinement for 8c.
Empirical formula
Molecular weight
Temperature
C19H18N4S
334.43
120(2) K
Wavelength
0.71073 Å
Crystal system, space group
Unit cell dimensions
a, α
b, β
c, γ
orthorhombic, Pbca
9.51557(6) Å, α= 90 °
15.8703(10) Å, β= 90 °
21.6351(12) Å, γ= 90 °
3267.3(3) Å3
Volume
Z; density calculated
Absorption coefficient
F(000)
8 mg.m-3
0.206 mm-1
1408
Crystal size
θ , Range for data collection
Range of h, k, l
0.65 X 0.25 X 0.10 mm
3.47- 25.00°
-8< = h< =12, -20< = k< = 20, -28< = l< = 27,
15684
Reflections collected
Independent reflections
Refinement method
Data; restraints; parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
Largest diff. Peak and hole
2865
full-matrix least-squares on F2
2818 / 0 / 289
1.020
R1= 0.0354, wR2 = 0.0827
R1= 0.0426, wR2 = 0.0856
0.240 and –0.262 e. Å-3
N-(2-Cyanophenyl)benzimidoyl isothicyanate - acetone solution (3).
A mixture of N-(2-cyanophenyl)benzamide (1) [22] (0.5 g, 2.25 mmol), and phosphorous
pentachloride (0.5 g, 2.4 mmol) was refluxed in dry toluene for 8 h. The solvent was removed under
reduced pressure to give a brownish colored oil of N-(2-cyanophenyl)benzimidoyl chloride (2) [23]
which was not further purified. To a solution of this crude oil in dry acetone a solution of potassium
thiocyanate (0.22 g, 2.25 mmol) in dry acetone was added portionwise with stirring and cooling at -

Molecules 2001, 6
584
5°C for 2 h. The precipitated potassium chloride was filtered off , thus leaving an acetone solution of
N-(2-cyanophenyl)benzimidoyl isothicyanate (3). 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).
1,1-Disubstituted-3-(2-phenyl-3H-quinazolin-4-ylidene)thioureas (8).
Procedure A
The appropriate secondary amine (2.25 mmol) was added in portions with stirring at room
temperature to the acetone solution of isothiocyanate 3 over a period of 1h. The reaction mixture was
then stirred for 24h. The precipitated quinazolines 8a-8d and 8f were filtered off and recrystallized
from ethyl alcohol. Spectral data are given below.
Procedure B
The reaction mixture consisting of the chloroform solution of thiourea derivative 4e (0.28 g) and
triethylamine (0.2 ml) was refluxed for 4h. The reaction mixture was evaporated under reduced
pressure to give the desired product 8e, which was recrystallized from ethyl alcohol.
Procedure C
Quinazoline 8a (0.2 g, 0.6 mmol) was dissolved in DMF (3mL) and 1.8 mmol of the corresponding
amine (N-methylpiperazine or 40% aqueous methylamine) was added to this solution. The reaction
mixture was heated under reflux at 150°C for 2-4 h. Afterwards the DMF was evaporated under
reduced pressure (80°C/ 2.67 kPa.) and the resultant product was recrystallized from ethyl alcohol.
Morpholine-1-carbothioic acid (2-phenyl-3H-quinazolin-4-ylidene) amide (8a).
From 3 (procedure A); Yield: 0.17 g (22%); M.p. 185-186oC; Calc. for C19H18N4OS (350.44): 65.12%
C, 5.18% H, 15.99% N, 9.15% S; found: 64.98% C, 5.05% H, 16.02% N, 9.00% S; FTIR: 3220 (NH),
1
2961,2923,2859 (CH), 1614 (C=N); H-NMR: 8.41– 7.39 (9H, m, ArH), 4.29-4.25 (4H, m, OCH2),
13
3.84 - 3.80 (4H, m, NCH2); C-NMR: 184.70 (C=S), 154.98 (C2), 149.60 (C4), 148.76 (Cq), 134.78
(CHAr), 132.43 (Cq), 132.09 (CHAr), 129.21 (CHAr), 128.21 (CHAr), 127.42 (CHAr), 127.26 (CHAr),
125.49 (CHAr), 121.17 (Cq), 66.82 (OCH2), 47.95 (NCH2), 47.79 (NCH2); Mass spectrum, m/z (Ir/%):
350 (5), 265 (16), 263 (82), 206 (9), 205 (100), 132 (11), 103 (15), 102 (39), 87 (25), 86(14), 77 (42),
76 (16), 57 (27) , 51 (14).
Piperidine-1-carbothioic acid (2-phenyl-3H-quinazolin-4-ylidene) amide (8b).
From 3 (procedure A); Yield: 0.23 g (29%); M.p. 135-136oC; Calc.for C20H20N4S (348.47): 68.94% C,
5.78% H, 16.08% N, 9.20% S; found: 68.79% C, 5.70% H, 16.10% N, 9.09% S; FTIR: 3180 (NH),

Molecules 2001, 6
585
1
2926,2852 (CH), 1610 (C=N); H-NMR: 8.42– 7.39 (9H, m, ArH), 4.25-4.29 (4H, m, NCH2), 1.70 –
13
1.74 (6H, m, CH2); C-NMR: 183.35 (C=S), 154.28 (C2), 149.70 (C4), 148.76 (Cq), 134.29 (CHAr),
132.65 (Cq), 131.62 (CHAr), 129.34 (CHAr), 128.14 (CHAr), 127.61 (CHAr), 127.15 (CHAr), 125.56
(CHAr), 121.17 (Cq), 49.06 (NCH2), 48.55 (NCH2), 26.53 (CH2), 25.92 (CH2), 24.82 (CH2); Mass
spectrum, m/z (Ir/%): 348 (3), 264 (18), 263 (75), 206 (19), 205 (100), 132 (8), 103(11), 102 (28), 85
(22), 84 (53), 77 (47) , 76 (19), 75 (15), 56 (12).
Pyrrolidine-1-carbothioic acid (2-phenyl-3H-quinazolin-4-ylidene) amide (8c).
From 3 (procedure A); Yield: 0.19 g (25%); M.p. 205-206oC; Calc. for C19H18N4S (334.44): 68.24%
C, 5.42% H, 16.75% N, 9.59% S; found: 68.07% C, 5.33% H, 16.60% N, 9.43% S; FTIR: 3200 (NH),
1
2968,2867 (CH), 1611 (C=N); H-NMR: 8.45– 7.44 (9H, m, ArH), 4.01 (2H, t, NCH2) (JA,B= 6.90
13
Hz), 3.87 (2H, t, NCH2) (JA,B= 6.90 Hz), 1.99-2.07 (4H, m, CH2); C-NMR: 183.19 (C=S), 155.66
(C2), 151.04 (C4), 149.18 (Cq), 134.72 (CHAr), 133.17 (CHAr), 132.11 (CHAr), 129.68 (CHAr), 128.59
(CHAr), 128.02 (CHAr), 127.34 (CHAr), 125.96 (CHAr), 121.84 (Cq), 52.21 (NCH2), 51.69 (NCH2),
27.05 (CH2), 26.31 (CH2); Mass spectrum, m/z (Ir/%): 334 (22), 301 (12), 265 (21), 264 (39), 263 (48),
232 (35),206 (25), 205 (100), 103 (12), 102 (24), 77 (38), 70 (30).
4-Methylpiperazine-1-carbothioic acid (2-phenyl-3H-quinazolin-4-ylidene) amide (8d).
From 3 (procedure A); Yield: 0.13 g (16%); M.p. 244-245oC; From 8a (procedure C); Yield: 0.1g
(48%); M.p. 244-245°C; Calc. for C20H21N5S (363.48): 66.09% C, 5.82% H, 19.27% N, 8.82% S;
1
found: 65.90% C, 5.70% H, 19.07% N, 8.69% S; FTIR: 3240 (NH), 2934, (CH), 1610 (C=N); H-
NMR: 8.43–7.48 (9H, m, ArH), 4.42-4.37 (4H, m, NCH2), 2.60-2.56 (4H, m, NCH2), 2.39 (3H, s,
CH3); 13C-NMR: 184.38 (C=S), 154.85 (C2), 149.51 (C4), 149.13 (Cq), 134.73 (CHAr), 132.86 (CHAr),
132.00 (CHAr), 129.37 (CHAr), 128.43 (CHAr), 127.60 (CHAr), 127.34 (CHAr), 125.65 (CHAr), 121.51
(Cq), 55.06 (NCH2), 54.71(NCH2), 47.21 (CH3NCH2), 46.78 (CH3NCH2), 45.53 (NCH3); Mass
spectrum, m/z (Ir/%): 363 (8), 264 (17), 263 (72), 206 (10), 205 (100), 131 (6), 103 (9), 102 (34), 100
(29), 99 (22), 83 (47), 77 (33), 75 (10), 74 (10), 70 (11), 58 (38) , 56 (10).
1,1--Dibutyl-3-(2-phenyl-3H-quinazolin-4-yliden) thiourea (8e).
From 4e (procedure B); Yield: 0.18 g (64%) (B, from 4e); M.p. 184-185oC; Calc. for C23H28N4S
(392.56): 70.37% C, 7.19% H, 14.27% N, 8.17% S; found: 70.21% C, 7.15% H, 14.11% N, 8.07% S;
FTIR: 3210 (NH), 2955, 2927, 2869 (CH), 1614 (C=N); 1H-NMR: 8.41– 7.08 (9H, m, ArH), 3.97 (4H,
t, NCH2) (JA,B= 7.12 Hz), 1.84-1.70 (4H, m, NCH2CH2), 1.51-1.34 (4H, m, CH2CH3), 1.04 (6H, t,
CH2CH3) (JA,B= 7.31 Hz); 13C-NMR: 184.21 (C=S), 154.23(C2), 149.83 (C4), 148.99 (Cq), 134.29
(CHAr), 132.96 (CHAr), 131.62 (CHAr), 129.34 (CHAr), 128.14 (CHAr), 127.61 (CHAr), 127.15 (CHAr),
125.56 (CHAr), 121.85 (Cq), 51.60 (NCH2), 51.27 (NCH2), 30.83 (NCH2CH2), 28.90 (NCH2CH2),
20.68 (CH2CH3), 20.59 (CH2CH3), 14.19 (CH2CH3), 14.11 (CH2CH3)

Molecules 2001, 6
586
1,1-Diphenyl-3-(2-phenyl-3H-quinazolin-4-ylidene) thiourea (8f)
o
From 3 (procedure A); Yield: 0.31 g (32%) M.p. 155 C; Calc. for C27H20N4S (432.54): 74.97% C,
4.66% H, 12.95% N, 7.41% S; found: 74.95% C, 4.45% H, 12.92% N, 7.39% S; FTIR: 3284 (NH),
3059 (CH), 1612 (C=N); 1H-NMR: 16.73 (1H, bs, NH), 8.32– 7.07 (19H, m, ArH); 13C-NMR: 188.30
(C=S), 158.71 (C2), 155.77 (CHAr), 151.53 (C4), 149.13 (Cq), 134.93 (CHAr), 134.29 (CHAr), 132.52
(Cq), 132.17 (CHAr), 131.62 (CHAr), 129.37 (CHAr), 127.57 (CHAr), 128.14 (CHAr), 127.53 (CHAr),
127.50 (CHAr), 126.09 (CHAr), 121.17 (Cq).
1,1-Dibutyl-3-[(2-cyanophenylimino)phenylmethyl] thiourea (4e).
Compound 4e was prepared via procedure A by the reaction of 3 with dibutylamine. Yield: 0.28 g
(32%); M.p. 134-135oC (DMF); Calc. for C23H28N4S (392.56): 70.37% C, 7.19% H, 14.27% N, 8.82%
S; found: 70.21% C, 7.01% H, 13.95% N, 8.63% S; FTIR: 3210 (NH), 2955, 2927, 2869 (CH), 1597
1
(C=C); H-NMR (CF3COOD): 8.56– 7.78 (9H, m, ArH), 4.09 (4H, t, NCH2), 2.14-1.94 (4H, m,
NCH2CH2), 1.70-1.55 (4H, m, CH2CH3), 1.11 (6H, t, CH2CH3); 13C-NMR (CF3COOD): 178.12 (C=S),
163.81 (N=C) 160.14 (Cq), 140.65 (CHAr), 139.64 (Cq), 138.50 (CHAr), 133.25 (CHAr), 132.47 (CHAr),
130.94 (CHAr), 128.07 (CHAr), 122.20 (CHAr), 117.80 (Cq), 107 (CN), 56.56 (NCH2), 56.10 (NCH2),
31.94 (NCH2CH2), 30.47 (NCH2CH2), 21.68 (CH2CH3), 14.23 (CH2CH3).
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Sample Availability: Available from the authors.
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