Synthesis and structural analysis of 3-phenylethyl-2,4(1H,3H)-quinazolinediones

Article abstract of DOI:10.1016/j.molstruc.2017.06.138

This article presents the unexpected synthesis of 3-phenylethyl-2,4(1H,3H)-quinazolinediones by means of oxidative expansion of the 3-phenylethylimino-2-indolinone ring promoted by sodium borohydride. The ¹H NMR spectroscopic patterns showed the presence of two conformational isomers in equilibrium, the first was a staggered conformation and the second was a gauche structure. The crystal structure of 3-phenylethyl-2,4(1H,3H)-quinazolinedione revealed a staggered conformation with the quinazoline fragment and the phenyl ring in anti-arrangement. The molecules of quinazolinedione are associated in centrosymmetric dimers through two N–H?O hydrogen bonds between the NH moieties and the adjacent carbonyl groups.

Full text of DOI:10.1016/j.molstruc.2017.06.138

Accepted Manuscript
Synthesis and structural analysis of 3-phenylethyl-2,4(1H,3H)-quinazolinediones
Rodolfo Quevedo, Yormari Vélez, Adrián Pérez-Redondo
PII:
S0022-2860(17)30919-5
10.1016/j.molstruc.2017.06.138
MOLSTR 24024
DOI:
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Revised Date:
Accepted Date:
02 June 2017
30 June 2017
30 June 2017
Please cite this article as: Rodolfo Quevedo, Yormari Vélez, Adrián Pérez-Redondo, Synthesis and
structural analysis of 3-phenylethyl-2,4(1H,3H)-quinazolinediones, Journal of Molecular Structure
(2017), doi: 10.1016/j.molstruc.2017.06.138
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ACCEPTED MANUSCRIPT
Synthesis and structural analysis of 3-phenylethyl-2,4(1H,3H)-
quinazolinediones
a
a
b
Rodolfo Quevedo *, Yormari Vélez and Adrián Pérez-Redondo
aUniversidad Nacional de Colombia, Sede Bogotá, Facultad de Ciencias, Departamento de
Química, Carrera 30 No. 45-03, Bogotá,
Colombia
bDepartamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28805 Alcalá de
Henares-Madrid, Spain
Abstract
This article presents the unexpected synthesis of 3-phenylethyl-2,4(1H,3H)-
quinazolinediones by means of oxidative expansion of the 3-phenylethylimino-2-
1
indolinone ring promoted by sodium borohydride. The H-NMR spectroscopic
patterns showed the presence of two conformational isomers in equilibrium, the first
was a staggered conformation and the second was a gauche structure. The crystal
structure of 3-phenylethyl-2,4(1H,3H)-quinazolinedione revealed a staggered
conformation with the quinazoline fragment and the phenyl ring in anti-arrangement.
The molecules of quinazolinedione are associated in centrosymmetric dimers
through two N-H···O hydrogen bonds between the NH moieties and the adjacent
carbonyl groups.
Keywords
Ring expansion
Oxidative cleavage
Isatin
Quinazolinedione
Schiff base

ACCEPTED MANUSCRIPT
1. Introduction
Isatin (1H-indole-2,3-dione) 1 is a benzofused cyclic ketone of great interest in
organic chemistry because it has a highly electrophilic carbonyl which is useful in the
synthesis of nitrogen heterocyclic and spiroheterocyclic systems [1,2]. Isatin-derived
Schiff bases are also of interest in organic and medicinal chemistry due to their
usefulness as substrates when preparing compounds having biological activity, such
as anti-HIV, anticonvulsant, antibacterial, antifungal and antiviral activity and their
capability for forming compounds with different metals [3-2].
It has been established recently that some phenylethylamines react with isatin to
form the respective Schiff bases (3-phenylethylimino-2-indolinones) 2 as a mixture
of E/Z stereoisomers; E is the kinetic product and Z is the thermodynamic product.
The mixture of isomers is obtained in variable proportions, depending on the
experimental conditions used (Scheme 1) [7].
Continuing our studies related to the chemical and structural behaviour of
phenylethylamine derivates and carbonyl compounds [8-10], this article describes a
study of the behaviour of Schiff bases produced by reaction of isatin 1 with
phenylethylamine 2a and with tyramine 2b regarding a reducing agent like sodium
borohydride. The results showed that (in the reaction conditions used here) no
reduction of Schiff bases occurred for the formation of the respective amine 3 and
the corresponding 3-phenylethyl-2,4(1H,3H)-quinazolinediones 4 were obtained as
the main product by means of a reaction involving the oxidative expansion of the
indolinone ring (scheme 2). This article provides a structural analysis of the 3-
phenylethyl-2,4(1H,3H)-quinazolinediones 4 obtained and proposes a mechanistic
explanation for the reaction.
2
. Experimental Section
.1. General
2

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1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded at room
temperature on a Bruker Avance 400 spectrometer. CDCl were used as solvent. IR
3
spectra were registered in a Nicolet iS10 spectrometer (Thermo Fisher Scientific,
-1
4
000 - 400 cm ) using KBr disks. Mass spectra were recorded on a Shimadzu
LCMS-IT-TOF liquid chromatograph mass spectrometer using electrospray
ionization (ESI). The ESI probe was operated in the positive mode using the
following parameters: CDL temperature, 200 °C; heating block, 200 °C; flow gas
(
N ), 1.5 L/min; detector voltage, 1.69 kV; and scan range, m/z 100-350. All reagents
2
and solvents were purchased and used without further purification. 3-
phenylethylimino-2-indolinones were prepared according to the literature procedures
[
7].
2.2. Crystallization and X-ray diffraction
Purple needles of compound 4 were grown from a toluene/chloroform (1:1) solution
by slow evaporation at room temperature. The crystals were removed from the vial
and covered with a layer of a viscous perfluoropolyether (FomblinY). A suitable
crystal selected with the aid of a microscope was mounted on a cryoloop and placed
in the low temperature nitrogen stream of the diffractometer. The intensity data sets
were collected at 200 K on a Bruker-Nonius KappaCCD diffractometer equipped with
an Oxford Cryostream 700 unit. The molybdenum radiation was used, graphite
monochromated, and enhanced with a MIRACOL collimator. Crystallographic data are
presented in Table 1.
The structure was solved, using the WINGX package [11], by direct methods
2
(
SHELXS-2013) and refined by least-squares against F (SHELXL-2014/7) [12,13].
These crystals showed disorder for the carbon atoms C(11)-C(16) of the phenyl ring.
This disorder was treated using the PART tool and allowing free refinement of the
occupancy factors with the FVAR command. The final values of occupancy were
50.8 and 49.2%. All non-hydrogen atoms were anisotropically refined. In addition the
position and the thermal parameters of C(11) and C(11)’ were constrained to be
identical. All hydrogen atoms were positioned geometrically and refined by using a

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riding model, except the hydrogen H(2), linked to N(2), which was located in the
difference Fourier map and isotropically refined.
2.3. 3-phenylethylimino-2-indolinone 2a reaction with sodium borohydride in
methanol.
Sodium borohydride (80 mg, 2.11 mmol) was added to a solution of 3-
phenylethylimino-2-indolinone 2a (460 mg, 1.84 mmol) in methanol (10 mL). The
mixture was stirred at room temperature for 24 hours. Once this time had elapsed,
water was added until the precipitate appeared. The precipitate was then filtered,
washed with water and dried at room temperature. A purple product was obtained:
1
4
02 mg, yield: 82%, mp 114-116°C, H-NMR (400 MHz, CDCl , 25°C): δ= 3.05 (CH -
3
2
Ph, t, JH,H= 8 Hz and dd, JH,H= 10 Hz and 6Hz, 2H), 4.36 (CH -N, t, JH,H= 8Hz and
2
dd, JH,H= 10 Hz and 6 Hz, 2H), 7.17 (H-C8, d, JH,H= 8 Hz, 1H), 7,67 (H-C6, t, JH,H
Hz, 1H), 8.17 (H-C5, d, JH,H=8Hz, 1H), 7.22-7.40 (m, 6H). 13C-NMR (100 MHz,
CDCl ): δ 162.0 (C4), 152.1 (C2), 138.58 (C9), 138.56 (C1'), 135.1(C7), 129.0
=
8
3
(C3',C5'), 128.5 (C2',C6'), 128.4 (C5), 126.5 (C4'), 123.4 (C6), 115.1 (C8), 114.7
-1
(
C10), 42.3 (C-N), 34.1 (C-Ph). FT-IR (KBr) cm : 3189, 1719, 1654. EI-MS:
266.07(16%), 162.10 (22%), 146.10 (40%), 104.18 (100 %). ESI-HRMS: m/z
+
2
67.1424 ([M+H] , calc. 267.1128).
2.4. 3-phenylethylimino-2-indolinone 2a reaction with sodium borohydride in
acetonitrile.
Sodium borohydride (80 mg, 2.11 mmol) was added to a solution of 3-
phenylethylimino-2-indolinone 2a (460 mg, 1.84 mmol) in acetonitrile (10 mL). The
mixture was stirred at room temperature for 24 hours. Once this time had elapsed,
HCl (5 %) was added until the precipitate appeared. The precipitate was then filtered,
washed with water and dried at room temperature. A purple product was obtained
(Mixture
of
3-phenylethyl-2,4(1H,3H)-quinazolinedione
4
and
3-[(2-
phenylethyl)amino]-1,3-dihydro-2H-indol-2-one 5 (2:0.88), quinazolinedione 4: yield:
1
5
6 %, and amine 3: yield: 25 %. H-NMR (400 MHz, CDCl ): δ 2.97 (CH -Ph, t, JH,H=
3
2
7
Hz, 2H), 3.77 (CH -N, t, JH,H= 7Hz, 2H), 4.41 (H-C, s,1H), 6.67 (H-C7, d, JH,H= 8
2

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Hz, 1H), 6.92 (H-C5, t, JH,H= 8Hz, 1H), 7.62 (H-C6, t, JH,H=8Hz, 1H), 7.97 (H-C4, d,
JH,H= 8 Hz, 1H). 13C-NMR (100 MHz, CDCl ): δ 139.2 (C8), 133.1 (C1'), 128.9
3
(
C3',C5'), 128.8 (C2',C6'), 128.7 (C4') , 128.3 (C6), 126.8 (C4), 126.5 (C5), 120.0
C9), 115.1 (C7), 60.4 (C3), 48.1 (C-N), 34.6 (C-Ph).
(
2.5. 3-(4-hydroxyphenylethyl)imino-2-indolinone 2b reaction with sodium
borohydride in methanol.
Sodium borohydride (40 mg, 1.05 mmol) was added to a solution of 3-(4-
hydroxyphenylethyl)imino-2-indolinone 2b (204 mg, 0.77 mmol) in methanol (10
mL). The mixture was stirred at room temperature for 24 hours. Once this time had
elapsed, water was added until the precipitate appeared. The precipitate was then
filtered, washed with water and dried at room temperature. A brown product was
1
obtained: 175 mg, yield: 81 %, mp 244-246 °C, H-NMR (400 MHz, CDCl , 25°C):
3
δ= 2.86 (CH -Ph, t, JH,H= 8 Hz and dd, JH,H= 8 Hz and 6Hz, 2H), 4.17 (CH -N, t, JH,H=
2
2
8Hz and dd, JH,H= 8 Hz and 6 Hz, 2H), 6.73 (H-C3', H-C5', d, JH,H= 10 Hz, 2H), 7.04
(H-C2', H-C6', d, JH,H= 10 Hz, 2H), 7.18 (H-C8, d, JH,H=8Hz, 1H), 7.24 (H-C6, t,
13
JH,H=8Hz, 1H), 7.65 (H-C7, t, JH,H=8Hz, 1H), 8.04 (H-C5, d, JH,H=8Hz, 1H). C-NMR
(
100 MHz, CDCl ): δ 32.6 (C-Ph), 42.0 (C-N), 114.1 (C10), 114.7 (C3', C5'), 114.8
3
(C8), 122.7 (C6), 127.4 (C5), 129.3 (C2', C6'), 129.4 (C1'), 134.8 (C7), 139.4 (C9),
-1
1
50.9 (C2), 155.6 (C4'), 162.8 (C4). FT-IR (KBr) cm : 3500-2500, 1716, 1639.
Found C: 67.65, H: 5.10, N: 9.71, calc. for C H N O : C: 68.07, H: 5.00, N: 9.92.
16
14
2
3
3. Results and Discussion
Our research group has been synthesising phenylethylamine-derived amines by
means of indirect reductive amination reactions using sodium borohydride as
reducing agent. The respective amine 3 was not formed when isatin- and
phenylethylamine-derived Schiff bases 2a were used in the same experimental
conditions (sodium borohydride in methanol for 24 h.). A purple solid (C H N O
2
16
13
2
molecular formula) was obtained whose structure was determined by 1D and 2D
1
NMR spectroscopy. H-NMR spectrum revealed characteristic signals for the ortho-

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disubstituted system from isatin 1 and for the monosubstituted ring from
phenylethylamine in the aromatic region; the aliphatic region showed signals
corresponding to the two methylenes from phenylethylamine. Different to that
expected for amine 3, no singlet signal corresponding to methine was observed
(which should appear around 4 ppm). Different from the starting Schiff base 2a, no
signal corresponding to the methine from the imino group was observed at 8.3 ppm.
In addition to the information obtained from the H-NMR spectrum, the 13C-NMR
spectrum revealed two signals (at 152 and 162 ppm) corresponding to carbonyl
groups assigned to two amide groups present in the molecule.
1
The correlations in HMBC spectrum (Fig.1) between methylene hydrogens and
carbonyl carbons and between some aromatic hydrogens and carbonyl carbons led
to confirming that the compound obtained was a 3-phenylethyl-2,4(1H,3H)-
quinazolinedione 4. Such compound should have been formed by means of a
sodium borohydride-induced oxidative expansion of 3-phenylethylimino-2-
indolinone 2a.
1
Methylenes in phenylethylamine-derived usually generate two triplets H-NMR
spectrum, appearing around 3 and 4 ppm. These two signals were observed at 3.05
1
and 4.37 ppm in 3-phenylethyl-2,4(1H,3H)-quinazolinedione 4 H-NMR spectrum;
however, multiplicity was different, as shown in Figure 2. Each methylene generated
a group of signals having greater complexity. This spectroscopic pattern can be
explained by the presence of two conformational isomers in equilibrium, one of the
conformers generating a triplet for each methylene and the other a double doublet;
both overlapping signals produced the pattern shown in Figure 2.
The Gaussian 03 software package was used for analysing possible 3-phenylethyl-
2,4(1H,3H)-quinazolinedione 4 conformers by means of DFT-B3LYP/6-31G(d,p)
computational calculations to obtain greater information about the spectroscopic
patterns. The results revealed two conformations having similar energy
(1.39Kcal/mol difference) (Fig. 3); the first was a staggered conformation having the

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aromatic ring and the quinazolinedione in an anti-relationship; the hydrogens from
each methylene in this structure were magnetically equivalent and appeared in the
spectrum as triplets. The second conformation was a gauche structure; the
hydrogens from each methylene in this conformation were in different settings,
producing double doublets having chemical shift similar to those observed for the
anti-conformation. Figure 2 shows the overlapping of these signals as a multiplet.
The Boltzmann factors were calculated at room temperature for each conformation
to predict the relationship between both conformers’ populations. The results
showed that the anti-conformer was mainly obtained (91%), the gauche conformer
much less so (only 9%); the experimental results showed that both conformers were
present in similar proportions in solution. However, a single-crystal X-ray diffraction
analysis of 4 revealed a staggered conformation with the quinazoline fragment and
the phenyl ring in anti-arrangement (Fig. 4) with a N(1)-C(9)-C(10)-C(11) torsion
angle of 175.5(2)º.
Molecules of 4 are associated in centrosymmetric dimers through two N-H···O
hydrogen bonds between the NH moieties and the adjacent carbonyl groups
(N(2)···O(1)i and H(2)···O(1)i distances of 2.817(2) and 1.94(2) Å respectively, and
N(2)-H(2)···O(1)i angle of 173(2)º, symmetry code: (i) –x, 1 – y, –z) (Figure 5). These
dimers are packed maintaining the quinazoline rings in a face-to-face stacking
arrangement (Figure 6), due to C-H···O hydrogen bonds (C(9)···O(2)ii length of
3.367(3) Å, symmetry code: (ii) x, 1 + y, z) and weak intermolecular ··· interactions
(centroid-centroid separations of 4.257 and 4.362 Å).
On the other hand, it has been proposed that a secondary alcohol and oxygen are
needed for the oxidative cleavage of sodium hydride-induced 2-hydroxyacetones
and 1,2-diones. An acid-base reaction between the hydroxyl from alcohol and the
hydride has been proposed as the first step; such acid-base reaction would favour
the oxidation of alcohol to ketone and the production of a hydride which would react
with oxygen to form hydroperoxide [14,15]. Such studies have led to concluding that
an equivalent of secondary alcohol reacting with an equivalent of sodium hydride

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and equivalent of oxygen would produce an equivalent of hydroperoxide; yield would
thus be low when working with atmospheric oxygen.
The synthesis of 3-phenylethyl-2,4(1H,3H)-quinazolinedione 4 by Schiff base 2a
reaction with sodium borohydride was done in methanol; it was thus initially thought
that a reaction mechanism analogous to that discussed above was involved. The
same procedure was carried with acetonitrile as solvent to confirm the participation
of alcohol in the oxide-reduction reaction necessary for ring expansion. 1H-NMR
analysis of the reaction product in acetonitrile revealed a mixture of two compounds;
the majority compound was the product of oxidative expansion (3-phenylethyl-
2,4(1H,3H)-quinazolinedione 4), whilst the minority product was the product of 3-
phenylethylimino-2-indolinone 2 reduction (3-[(2-phenylethyl)amino]-1,3-dihydro-
1
2
H-indol-2-one 3); the ratio of the integrals in H-NMR spectrum revealed two
products (2:1 ratio) (scheme 3). This result led to demonstrating that an alcohol is
not necessary for the oxidative expansion of the ring to occur and that the direct
interaction between sodium borohydride and atmospheric oxygen produces the
hydroperoxide needed for the reaction.
Considering the forgoing observations, 3-phenylethyl-2,4(1H,3H)-quinazolinedione
4
formation can be rationalised by means of the initial formation of hydroperoxide by
the interaction, probably via free radicals between sodium borohydride and
atmospheric oxygen. Hydroperoxide anion nucleophile attack on imino induces
Baeyer-Villiger oxidation, leading to the formation of the respective 4-imino-(1H,4H)-
3,1-benzoxazine-2-one 5. The acid-base interaction between the nitrogen from
benzoxazine-2-one 5 and the reaction medium leads to the opening of the cycle with
the formation of the respective intermediary, isocyanate carboxamide 6, a previously
proposed mechanism for the rearrangement of 4-imino-(1H,4H)-3,1-benzoxazine-2-
one to 2,4-quinazolinedione [16]. The intramolecular nucleophilic attack by the
nitrogen from carboxamide on isocyanate leads to the formation of the respective
quinazolinedione 4 (Scheme 4).

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Previous studies have shown that phenolic hydroxyls on the phenylethylamine ring
affect both aromatic ring and nitrogen reactivity [17]. Tyramine-derived Schiff base
2b was put to react with sodium borohydride in methanol for establishing whether
the presence of phenolic hydroxyls affected the course of the reaction regarding the
oxidative expansion of 3-phenylethylimino-2-indolinones 2 (whether due to the
presence of acid hydrogens from phenol or to changes in nucleophilicity of the
nitrogen); this reaction led to the formation of the respective quinazolinedione 7 as
sole product, having good yield (scheme 5). The reproducibility observed regarding
both the course of the reaction and purification enables explaining the oxidative
expansion of isatin-derived Schiff bases induced by sodium borohydride as a simple,
economic and efficient methodology for quinazolinedione synthesis.
4. Conclusions
This paper has thus presented a new synthesis of 3-phenylethyl-2,4(1H,3H)-
quinazolinediones by the oxidative expansion of the 3-phenylethylimino-2-
indolinone. The crystal structure of 3-phenylethyl-2,4(1H,3H)-quinazolinedione
revealed a staggered conformation with the quinazoline fragment and the phenyl
ring in anti-arrangement. The molecules of quinazolinedione are associated in
centrosymmetric dimers through two N-H···O hydrogen bonds between the NH
moieties and the adjacent carbonyl groups.
Acknowledgements
We would like to thank the National University of Colombia (DIB research project No.
37398) and Universidad de Alcalá (CCG2016/EXP-028) for providing financial
support.

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Supplementary data
CCDC-1546873 contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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O
O
N
N
R
NH2
NH
NH
O
R
+
O
N
H
Z isomer
E isomer
1
R
2a: R=-H 2b: R=-OH
Scheme 1. 3-phenylethylimino-2-indolinone 2 synthesis from isatin 1 and
phenylethylamines.
O
NH
N
N
NH
NaBH4
MeOH
NaBH4
MeOH
O
O
N
H
N
H
O
3
2a
4
Scheme 2. 3-phenylethylimino-2-indolinones 2 reaction with sodium borohydride in
methanol.
H
O
H
H
N
N
H
O
H
Figure 1. Selected HMBC correlations of 3-phenylethyl-2,4(1H,3H)-
quinazolinedione 4.

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4
.38
4.30
3.08
3.00
1
Figure 2. H-NMR spectrum for 3-phenylethyl-2,4(1H,3H)-quinazolinedione 4,
aliphatic region.
Anti
gauche
Figure 3. Conformers in solution for 3-phenylethyl-2,4(1H,3H)-quinazolinedione 4.

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Table 1. Experimental data for the X-ray diffraction study on compound 4
formula
Mr
T [K]
C H N O
16 14 2 2
266.3
200

[Å]
0.71073
crystal system
space group
a [Å]
monoclinic
P2 /c
1
14.004(1)
b [Å];  [º]
c [Å]
4.955(1); 102.19(1)
19.472(4)
1320.7(4)
4
V [Å3]
Z
-
3
calcd [g cm ]
1.339
-
1
MoK [mm ]
F(000)
crystal size [mm3]
0.090
560
0.40 × 0.18 × 0.12
3.28−27.50
−17 to 18

range (deg)
index ranges
−
6 to 6
–25 to 25
reflns collected
unique data
28362
3034[R(int)= 0.091]
1797
obsd data [I > 2(I)]
2
GOF on F
1.036
a
Final R indices [I > 2(I)]
R1 = 0.055
wR2 = 0.123
R1 = 0.113
wR2 = 0.157
a
R indices (all data)
-3
largest diff. peak/hole [e Å ] 0.249 and −0.220
a
2
2)2]/[∑w(F
2 2 1/2
R1 = ∑ǀǀF
0
ǀ−ǀF
c
ǀǀ/[∑ǀF
0
ǀ]; wR2 = {[∑w(F
0
– F
c
0
) ]}

ACCEPTED MANUSCRIPT
Figure 4. ORTEP diagram of 3-phenylethyl-2,4(1H,3H)-quinazolinedione 4. Thermal
ellipsoids are drawn at the 50% probability level.
Figure 5. Molecules of 4 connected in dimers by N-H···O hydrogen bonds (in
orange). Symmetry code: (i) –x, 1 – y, –z.

ACCEPTED MANUSCRIPT
Figure 6. -stacking arrangement of 4 with C-H···O hydrogen bonds in green and

··· interactions in pink. Symmetry code: (ii) x, 1 + y, z.
O
NH
N
N
4
NH
NaBH4
+
O
O
CH CN
3
O
N
H
N
H
2a
3
Scheme 3. 3-phenylethylimino-2-indolinones 2 reaction with sodium borohydride in
acetonitrile.

ACCEPTED MANUSCRIPT
NaBH4 + O2
BH3 + NaOOH
+
-
N
Na N
N
O
-
_
OH
O OH
O
O
O
N
H
N
H
O
N
5
2a
H
-
OH
O
O
N
N
NH
..
O
N
H
O
4
6
Scheme 4. The mechanism proposed for 3-phenylethylimino-2-indolinones 2
reaction with sodium borohydride.
HO
HO
O
O
NH
N
N
NH
NaBH4
MeOH
O
2b
7
Scheme 5. 3-phenylethylimino-2-indolinone 7 reaction with sodium borohydride.

ACCEPTED MANUSCRIPT
Highlights
-
A new synthesis of 3-phenylethyl-2,4(1H,3H)-quinazolinediones is presented.
The X-ray structure of 3-phenylethyl-2,4(1H,3H)-quinazolinedione was reported for
-
the first Time. The structural analysis revealed a staggered conformation with the
quinazoline fragment and the phenyl ring in anti-arrangement.
-Molecules of 3-phenylethyl-2,4(1H,3H)-quinazolinedione are associated in
centrosymmetric dimers through two N-H···O hydrogen bonds between the NH
moieties and the adjacent carbonyl groups.

ACCEPTED MANUSCRIPT
Graphical abstract
Synthesis and structural analysis of 3-phenylethyl-2,4(1H,3H)-
quinazolinediones