Synthesis, characterization, and crystal structure of 3-(1,2,3,4- tetrahydroquinazoline-2-yl)phenol - A ring-chain tautomerized 2-substituted 1,2,3,4-tetrahydroquinazoline

Article abstract of DOI:10.1080/15421406.2013.803382

Synthesis, spectroscopic investigations, and X-ray crystal structure of 2-substituted-1,2,3,4-tetrahydroquinazoline ring, obtained from 3-hydroxy benzaldehyde and 2-(aminomethyl)aniline are presented. The X-ray structure and spectroscopic evidence show that the product, which is a ring chain tautomerized Schiff base, appears in a 100% ring form, both in the liquid and in the solid state. The crystal structure of the compound presents a unique supramolecular architecture consisting of hexamers, offering channels of radius 5.79 A down the c axis.

Full text of DOI:10.1080/15421406.2013.803382

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Synthesis, Characterization, and
Crystal Structure of 3-(1,2,3,4-
Tetrahydroquinazoline-2-yl)phenol—A
Ring-Chain Tautomerized 2-Substituted
1,2,3,4-Tetrahydroquinazoline
Amanpreet Kaur a , Geeta Hundal a & Maninder Singh Hundal a
a Department of Chemistry, UGC Sponsored Centre for Advanced
Studies-I , Guru Nanak Dev University , Amritsar , Punjab , India
Published online: 03 Oct 2013.
To cite this article: Amanpreet Kaur , Geeta Hundal & Maninder Singh Hundal (2013) Synthesis,
Characterization, and Crystal Structure of 3-(1,2,3,4-Tetrahydroquinazoline-2-yl)phenol—A Ring-Chain
Tautomerized 2-Substituted 1,2,3,4-Tetrahydroquinazoline, Molecular Crystals and Liquid Crystals,
582:1, 115-121, DOI: 10.1080/15421406.2013.803382
To link to this article: http://dx.doi.org/10.1080/15421406.2013.803382
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Mol. Cryst. Liq. Cryst., Vol. 115: pp. 115–121, 2013
Copyright © Taylor & Francis Group, LLC
ISSN: 1542-1406 print/1563-5287 online
DOI: 10.1080/15421406.2013.803382
Synthesis, Characterization, and Crystal Structure
of 3-(1,2,3,4-Tetrahydroquinazoline-2-yl)phenol—A
Ring-Chain Tautomerized 2-Substituted
1,2,3,4-Tetrahydroquinazoline
AMANPREET KAUR, GEETA HUNDAL, AND MANINDER
SINGH HUNDAL∗
Department of Chemistry, UGC Sponsored Centre for Advanced Studies-I, Guru
Nanak Dev University, Amritsar, Punjab, India
Synthesis, spectroscopic investigations, and X-ray crystal structure of 2-substituted-
1,2,3,4-tetrahydroquinazoline ring, obtained from 3-hydroxy benzaldehyde and 2-
(aminomethyl)aniline are presented. The X-ray structure and spectroscopic evidence
show that the product, which is a ring chain tautomerized Schiff base, appears in a
100% ring form, both in the liquid and in the solid state. The crystal structure of
the compound presents a unique supramolecular architecture consisting of hexamers,
offering channels of radius 5.79 Å down the c axis.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Mol. Cryst. Liq. Cryst. to view the free supplemental file.
Keywords Imine group; quinazoline ring; supramolecular hexamers; tautomerized
Schiff base
1. Introduction
The ring-chain tautomerism of five- and six-membered 1,3-X,Y-heterocycles (X, Y =
O, S, NR) is known to occur in heterocyclic systems closely related to quinazolines,
such as 1,3-imidazolidines and piperimidines, and their oxygen-containing analogs, 1,3
and 3,1-benzoxazines [1–6]. The ring-chain tautomerism of 3-substituted tetrahydro- and
decahydro-quinazolines has been investigated in the last decade by Fu¨lo¨p and coworkers
[7, 8]. Sinkkonen et al. used NMR spectroscopy to study this phenomenon on a set of
2-substituted 1,2,3,4-tetrahydroquinazolines, derived from 2-aminomethylaniline and var-
ious carbonyl compounds [9]. In 2-aryl substituted compounds, the ring-chain ratio has
been found to depend on the electronic character of the substituent on the aromatic ring
[10–12]. Two X-ray crystal structures of 2,3-substituted [13, 14] and four crystal structures
of 2-substituted-1,2,3,4-tetrahydroquinazolines [15] have been reported, which show the
existence of a ring conformer in the solid state.
∗Address correspondence to Maninder Singh Hundal, Department of Chemistry, UGC Sponsored
Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar 143005, Punjab, India. E-mail:
hundal chem@yahoo.com
115

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A. Kaur et al.
5
8
4
4a
8a
3
NH2
6
OH
NH
-H2O
15
OH
13
14
11
2
7
N
H
9
NH2
10
CHO
12
Scheme 1. Synthetic route to the compound (I).
Here, we report the synthesis, spectroscopic, and X-ray crystal structural studies of
a new 2-substituted-1,2,3,4-tetrahydroquinazoline compound, synthesized from 3-hydroxy
benzaldehyde and 2-(aminomethyl)aniline (Scheme 1), which appears in a 100% ring
form both in the liquid and in the solid state. Using NMR spectroscopy, Fu¨lo¨p et al. [6] had
reported 38.0% and 76.9% ring conformer with the products obtained from 2-(aminomethyl)
aniline with 4-hydroxy- and 2-hydroxy-benzaldehyde, respectively, in solution. Correa et al.
[15] have also synthesized a number of 2-aryl-1,2,3,4-tetrahydroquinazolines in a solvent-
free environment. However, a product from 3-hydroxybenzaldehyde has not been reported
earlier.
2. Experimental
2.1. Materials and Instrumentation
C, H, N elemental analysis was obtained with a CHNS-O analyzer flash-EA-1112 series.
1
The melting point was determined with electrically heated apparatus. H NMR spectrum
of compound was recorded on AL-300 FT JEOL spectrometer operating at a frequency of
300 MHz in dimethylsulfoxide (DMSO)-d6 with tetramethylsilane (TMS) as internal refer-
ence. The IR spectrum of compound was recorded on Perkin ELMER FT-IR spectrometer
in the range 4000–400 cm−1. Mass of the compound was recorded on Bruker compass
microTOF-Q11. Single crystal structural X-ray diffraction was carried out on a Bruker’s
Apex-II CCD diffractometer using Mo Kα (λ = 0.71069) at room temperature.
2.2. Synthesis of [3-(1,2,3,4-Tetrahydroquinazoline-2-yl)phenol]
3-Hydroxy benzaldehyde (1.0 mmol) was added to the methanol solution (60 ml) followed
by 2-(aminomethyl)aniline (1.0 mmol). After mixing, the clear solution formed was stirred
for 24 hours and later kept undisturbed for 7–8 days. Light yellow crystalline compound is
formed. Recrystallization in NH4OH allowed the isolation of light yellow colored crystals,
which were suitable for X-ray diffraction. Yield 68%; Mp: 148–150◦C; Calculated for
C14H14N2O1, (226.27 g/mol): Calculated C, 74.31%; H, 6.24%; N,12.38%; Found C,
74.42%; H, 6.47%; N, 12.69%; MS: m/z 227.117 [M+, 100%], 210.091[M-OH]+. IR (KBr,
ν/cm−1): 3355 (OH), 2932 (C–H), 3266 (N-H), 1606 (C=C). 1H NMR (300 MHz, DMSO-
d6): δ = 7.12(1H, t, J = 8.1, 7.9 Hz, –CHaromatic), δ = 6.89 (3H, m, –CHaromatic), δ =
6.79(1H, d, J = 7.5 Hz, –CHaromatic), δ = 6.67(1H, d, J = 7.5 Hz, –CHaromatic), δ = 6.56(1H,
d, J = 7.9 Hz, –CHaromatic), δ = 6.47(1H, t, J = 7.9, 8.1 Hz, –CHaromatic), δ = 3.67, 3.90
(dd, J = 16.52 Hz, CH2), δ = 6.1 (1H, CH) δ = 9.3 (1H, OH), δ = 4.9 (1H, NH), δ = 2.6
(1H, NH).

3-(1,2,3,4-Tetrahydroquinazoline-2-yl)phenol
117
Table 1. Crystal data and structure refinements for compound
Identification code
shelxl
Empirical formula
Formula weight
C14 H14 N2 O
226.27
Temperature
296(2) K
Wavelength
0.71073 Å
Crystal system, space group
Unit cell dimensions
Trigonal, R-3
a = 33.682(3) Å α = 90◦
b = 33.682(3) Å β = 90◦
c = 5.4395(4) Å γ = 120◦
5344.1(7) Å3
Volume
Z, calculated density
Absorption coefficient
F(000)
18, 1.266 Mg · m−3
0.081 mm−1
2160
Crystal size
0.12 × 0.10 × 0.09 mm3
2.09◦ to 28.71◦
28.71, 99.2%
Theta range for data collection
Completeness to theta
Absorption correction
Refinement method
Data/restraints/parameters
Final R indices [I > 2 sigma(I)]
R indices (all data)
Largest diff. peak and hole
CCDC number
Mixed
Full-matrix least-squares on F◦2
3057/3/163
R1 = 0.0535, wR2 = 0.0983
R1 = 0.1569, wR2 = 0.1311
0.140 e·Å−3 and −0.177 e·Å−3
926959
2.3. X-Ray Crystallography
X-ray data were collected on a Bruker’s Apex-II CCD diffractometer using Mo Kα (λ =
0.71069) at room temperature. Lorentz and polarization effects and empirical absorption
corrections were applied using Siemens Area Detector Absorption Correction (SADABS)
computer program. The structure was solved by direct methods, using SIR-92 software
[16] and refined by full-matrix least squares refinement [17] methods based on F2, using
SHELX-97. The hydrogen atoms of amines and hydroxyl group were located from the
difference Fourier synthesis and were refined isotropically with Uiso values 1.2 times that
of their carrier oxygen and nitrogen atoms, with fixed distances (O–H 0.82 Å and N–H
0.88 Å). All nonhydrogen atoms were refined anisotropically. All other hydrogen atoms
were fixed geometrically with their Uiso values 1.2 times of the phenylene and methylene
carbons. The structure shows solvent accessible voids (SAV) of volume 68 Å3, which are
due to the crystal packing forces, and there is no significant residual electron density.
All calculations were performed using Wingx package [18]. The crystal and refinement
parameters are given in Table 1.
3. Results
3.1. Spectroscopic Studies
The experimental result for the C, H, N, analysis are in good agreement with those cal-
culated for compound (I) C14H14N2O formed in the reaction. The IR spectrum (Fig. S1,

118
A. Kaur et al.
Figure 1. Showing Oak Ridge Thermal Ellipsoidal Plot (ORTEP) diagram of compound (I).
Supplemental Material, available online) of this compound shows a broad peak of O H
group present in the region of 3355 cm−1 due to strong hydrogen bonding interactions. The
peaks at 3266, 2932, 1606 cm−1 due to presence of N H, C H, C=C stretching vibrations,
respectively. The mass spectrum (Fig. S2, Supplemental Material, available online) of the
compound supports its formation. The base peak at 227.117 corresponds to the molecular
ion peak. Another peak at 210.091 indicates the ionization of meta-substituted –OH group.
1H NMR spectrum (Fig. S3, Supplemental Material, available online) of compound
was recorded in DMSO. Proton of the OH group shows a sharp singlet at δ 9.3 ppm.
The proton 1 and 3 of amine group –NH show signals at δ 4.9 and δ 2.6 ppm, respectively.
Protons 6 and 11 of aromatic ring show triplets at δ 6.47 ppm and δ 7.12 ppm, respectively
(Fig. S4, Supplemental Material, available online). Protons 8, 10, 12 of aromatic ring are
showing doublets at δ 6.67, δ 6.56, δ 6.79 ppm. Protons 5, 7, 14 are accidentally equivalent
and appearing together at δ 6.89 ppm. Magnetically inequivalent protons of the methylene
group at position 4 show two doublets at δ 3.67 and δ 3.92 ppm, with J values of 16.5 Hz
and proton of methine group CH at position 2 shows a singlet at δ 6.1 ppm. The DMSO
solvent also shows absorption at δ 2.49 ppm and water in the DMSO at δ 3.3 ppm. The
Figure 2. Showing molecular structure of compound where phenyl ring is nearly perpendicular to
the quinazoline ring.

3-(1,2,3,4-Tetrahydroquinazoline-2-yl)phenol
119
Figure 3. H-bonded atoms in compound (I) showing a helical channel about the c axis.
1
imine proton is absent in the H-NMR spectrum, which should appear in the range of δ
8.2–8.5 ppm in the chain form. Therefore, the NMR clearly indicates that the molecule
is present in the ring form and not in the chain form in the solution state also. No signal
corresponding to the chain form has been seen.
3.2. Single Crystal X-Ray Diffraction Studies
The compound crystallizes in the trigonal unit cell having R-3 space group. The ORTEP
diagram of the molecule (Fig. 1) shows that compound is a ring-chain tautomerized Schiff
Figure 4. Showing channels down the c axis formed due to self-assembly of the hexamers.

120
A. Kaur et al.
Figure 5. Showing CH–π interactions between two different molecules of compound (I).
base and is present in the ring form. All the bond parameters are normal. Tetrahydroquina-
zoline ring is not planar, because the methine group is significantly out of the plane by
0.53 Å. This ring is perpendicular to the phenol (Fig. 2), which is planar. These two make
a dihedral angle of 72◦ between them. The molecular structure is similar to the earlier
reported X-ray crystal structures of four compounds of 2-aryl substituted tetrahydroquina-
zoline rings [15], which also showed a perpendicular disposition of aryl ring with respect
to the tetrahydroquinazoline ring.
Due to presence of OH group at meta position, typical intermolecular hydrogen bonding
interactions are present. The –OH group is H-bonded to the amine group N2. These
interactions give rise to H-bonded hexamers (Fig. 3) positioned about the sixfold axis
of rotation, producing a channel of radius about 5.79 Å (Fig. 4) down the c axis. This
supramolecular arrangement is further supported by the second amine group, along the
c axis when the amine nitrogen N1 donates H-bond to the phenol oxygen (Table S1,
Supplemental Material, available online). There are important CH–π interactions also
between the methane carbon C13 and the phenol ring and the methylene carbon C14 and the
aromatic ring of tetrahydroquinazoline ring, with distances to the centroid being 3.841 Å
and 3.602 Å, respectively (Fig. 5). The supramolecular architecture of this crystal structure
is very much different from that of its analogous compound with the –OH group at para
position [15], which crystallizes in an orthorhombic Pbca space group. The intermolecular
H-bonding interactions between the amine and hydroxyl group produce a linear zig-zag
chain running along the b axis, whereas in 2-(2ꢀ-nitrophenyl)-1,2,3,4-tetrahydroquinazoline,
N–H. . . O(NO2 group) interactions form a linear tape along the b axis [15].
4. Conclusions
The condensation product of 3-hydroxybenzaldehyde and 2-benzylamine-aniline has been
found to be a tautomerized Schiff base, which is present solely in the ring form, both
in the solution and in the solid state. The analogous products with 2-hydroxy and 4-
hydroxybenzaldehyde are known to exist as tautomers in solution with 38% and 77% ring
form, respectively, whereas the latter appears only in the ring form as solid. Our results
in combination with the literature emphasize that the ring form is the only form stable in

3-(1,2,3,4-Tetrahydroquinazoline-2-yl)phenol
121
the solid state. The presence of another group, capable of H-bonding on the aryl ring at
position 2, generates interesting supramolecular arrangements.
Supplementary Information
NMR, IR, mass along with H-bonding tables. The cif and structure factor data are available
from Cambridge structure data base, free of cost, ccdc number = 926959.
Acknowledgments
MSH and GH are thankful to CSIR (India) for grant No. 01 (2406)/10/EMR-II. AK is
thankful to DST-INSPIRE Fellowship for Junior Research Fellowship.
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