Facile synthesis and spectral characterization of 2, 5-bis (cyclohexylamino)-1, 4-benzoquinone polymorphs from methyl and?ethyl protocatechuic aldehydes

Article abstract of DOI:10.1016/j.molstruc.2017.03.106

Two polymorphs of 2,5-bis(cyclohexylamino)-1,4-benzoquinone (BCBQI&BCBQII) are synthesized by an efficient alternate method which includes the oxidation of an aromatic aldehyde to benzoquinone moiety followed by its nucleophilic substitution in a single pot. The synthesized polymorphs have been characterized and distinguished by spectral and single crystal X-ray diffraction methods. A possible mechanism for the conversion is also suggested.

Full text of DOI:10.1016/j.molstruc.2017.03.106

Accepted Manuscript
Facile synthesis and spectral characterization of 2, 5-bis (cyclohexylamino)-1, 4-
benzoquinone polymorphs from methyl and ethyl protocatechuic aldehydes
A. Asha, A. Sheena Mohan, S. Suma, M.R. Sudarsanakumar, M.R. Prathapachandra
Kurup
PII:
S0022-2860(17)30395-2
10.1016/j.molstruc.2017.03.106
MOLSTR 23602
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 21 February 2017
Revised Date: 27 March 2017
Accepted Date: 28 March 2017
Please cite this article as: A. Asha, A.S. Mohan, S. Suma, M.R. Sudarsanakumar, M.R.P. Kurup, Facile
synthesis and spectral characterization of 2, 5-bis (cyclohexylamino)-1, 4-benzoquinone polymorphs
from methyl and ethyl protocatechuic aldehydes, Journal of Molecular Structure (2017), doi: 10.1016/
j.molstruc.2017.03.106.
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ACCEPTED MANUSCRIPT

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FACILE SYNTHESIS AND SPECTRAL CHARACTERIZATION OF 2, 5-BIS
(CYCLOHEXYLAMINO)-1, 4-BENZOQUINONE POLYMORPHS FROM METHYL
AND ETHYL PROTOCATECHUIC ALDEHYDES
A. Ashaa, A. Sheena Mohana, S. Sumaa*, M.R. Sudarsanakumarb,
M.R. Prathapachandra Kurupc
aDepartment of Chemistry, Sree Narayana College, Chempazhanthy,
Thiruvananthapuram-695587, India
bDepartment of Chemistry, M.G. College, Thiruvananthapuram-695004, India
cDepartment of Applied Chemistry, Cochin University of Science and Technology,
Kochi-682022, India
*Corresponding Author
E-mail address: sumasncw@gmail.com
Abstract
Two polymorphs of 2,5-bis(cyclohexylamino)-1,4-benzoquinone (BCBQI&BCBQII) are
synthesized by an efficient alternate method which includes the oxidation of an aromatic aldehyde to
benzoquinone moiety followed by its nucleophilic substitution in a single pot. The synthesized
polymorphs have been characterized and distinguished by spectral and single crystal X-ray diffraction
methods. A possible mechanism for the conversion is also suggested.
Keywords: Methyl & ethyl protocatechuic aldehyde, polymorphs, aminobenzoquinone, Single
crystal X-ray diffraction
Introduction
Methyl and ethyl protocatechuic aldehydes renowned under the names vanillin and ethyl vanillin
are phenolic aldehydes having wide spread applications in food industry. Both the homologues are used
as flavor enhancers and also as intermediate in the manufacture of certain pharmaceuticals and
agrochemicals. The ethyl analogue is a broad spectrum flavor than former and is one of the most
important synthetic fragrances in today’s world.
In the world of synthetic chemistry, vanillin and ethyl vanillin are used extensively in the
synthesis of Schiff bases and their metal complexes [1-4]. Extensive studies are carried out in the
synthesis of Schiff bases by condensing a primary amine and active carbonyl compounds. From prolific
literatures available for Schiff bases, those correlate cyclohexylamine and vanillin/iso vanillin/o-vanillin
are being referred here. Schiff bases from vanillin and vanillal esters are synthesized by refluxing them
with cyclohexylamine in methanol medium and all of them are low melting solids [5,6]. Azomethines has
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also been synthesized by condensing o-vanillin with aliphatic amines like methyl amine, 2-aminopyridine
and cyclohexylamine [7]. Schiff bases synthesized by condensing 2,3,4-trimethoxybenzaldehyde and
cyclohexylamine can react with palladium(II) acetate in glacial acetic acid to give the acetato-bridged
dimer complexes which react with sodium chloride or sodium bromide to give the corresponding halo-
bridged dimers [8].
Among biologically significant natural products, ortho and para benzoquinones and their amino
derivatives play a crucial role [9]. Profuse literature are available for the synthesis of naturally occurring
benzoquinones [10-14]. N-substituted aminobenzoquinones are typically studied for structure/color
relationships [15]. The redox potentials as well as the biological properties of 1,4-benzoquinone skeleton
can be modified by the presence of suitable donor or acceptor substituents [16]. The presence of
substituents carrying
π-electrons and unshared electron pairs of adjacent oxygen or nitrogen atoms
enhances the electron-donor properties of these quinones [17]. With the ability of undergoing reversible
oxidation-reduction process, p-benzoquinones find applications in dye industry. It is also worthwhile to
mention that 1,4-benzoquinone moiety forms part of ubiquinone, plastoquinone, maesaquinone,
blatellaquinone etc which play vital role in biological processes including electron transport, aerobic
cellular respiration, photosynthesis and plant mitochondrial respiration. Park and Crawford isolated
lumiquinone A, an α-aminomalonate derived aminobenzoquinone from the entomopathogenic bacterium
Photorhabdus luminescens TT01 from Photorhabdus luminescens [18].
Apart from the biosynthesis of amino benzoquinones [19], usual synthetic procedure starts from
1,4-benzoquinone or its derivatives and its subsequent nucleophilic substitution by corresponding amines.
2,5-bis (dialkylamino)-1,4-benzoquinones are synthesized by the oxidative amination of p-benzoquinone
in presence of fused sodium acetate [20] and copper(II) acetate [21]. Miroslaw Dworniczak reported the
concerted vinylic substitution of chlorine atoms by cyclohexylamino group at 2, 5 position in 2,3,5,6-
tetrachloro-1,4-benzoquinone. The reaction has been studied spectrophotometrically in acetonitrile
medium and kinetics and activation parameters are also reported [22]. 2,5-Diamino-1,4-benzoquinone
was synthesized by the hydrogenolysis of 2,5-Diamino-3,6-dibromoquinone over palladium-on charcoal.
Reaction procedure involves four steps with an overall yield of 82% [23]. 2, 5-dimethoxyaniline
derivatives are oxidized into protected amino-1, 4-benzoquinones by using PhI (OAc) 2 or PhI-(OCOCF3)2
in water containing 2.5% methanol [24].
The title compound 2, 5-bis(cyclohexylamino)-1,4-benzoquinone (BCBQ) has already been
synthesized by the conventional nucleophilic substitution of 1,4-benzoquinone with cyclohexylamine
[25]. The synthetic procedure involves 12 hour refluxing of 1, 4-benzoquinone with cyclohexylamine in
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methanol medium under aerobic conditions with 80% yield. Single crystals of BCBQ was obtained by
recrystallization of the precipitate from methanol solution. It has been characterized by spectral and single
crystal X-ray diffraction methods. Herein we are reporting an efficient alternate method for the synthesis
of BCBQI and BCBQII from ethyl vanillin/ vanillin and cyclohexylamine in methanol medium under
aerobic conditions. The polymorphs obtained show a difference only in the crystal structures. To the best
of our knowledge no reports are available citing the existence of BCBQ polymorphs. Our synthetic
pathway includes 1 hour refluxing of vanillin/ethyl vanillin with cyclohexylamine in methanol medium in
presence of air and few drops of glacial acetic acid. Bright red crystals were separated within 7 days from
the refluxed mixture which were subjected to single crystal X-ray diffraction study. A mechanism for the
formation of BCBQI and BCBQII along with their complete characterization is also proposed.
Polymorphism is the ability of a molecule to exist in different crystalline forms. Polymorphs are
generally characterized by the difference in some or all of the properties. They can be distinguished by
various techniques of which single crystal X-ray diffraction, DSC and Raman spectrum along with FTIR
need to be mentioned.
2. Experimental
2.1 Materials
Cyclohexylamine,ethyl vanillin and vanillin were of A R grade purchased from Merck and were used
without any purification. Solvent used was purchased from Merck and used as received.
2.2 Synthesis of 2, 5-bis (cyclohexylamino) 1, 4-benzoquinone (BCBQ)
Cyclohexylamine (1.98 g, 20 mmol) in 20 mL methanol was refluxed with ethyl vanillin
(1.66 g, 10 mmol) / vanillin (1.53 g, 10 mmol) in 20 mL MeOH in 2:1 ratio containing 6 drops of glacial
acetic acid for 1 hour (Scheme1). Initial yellow color of the solution gradually changed to deep red with
the progress of the reaction. Needle shaped bright red crystals of BCBQI suitable for X-ray diffraction
study separated out within seven days when the aldehyde is ethyl vanillin whereas dark red block crystals
were obtained for vanillin (BCBQII). It was filtered, washed with cold methanol and dried (m.p. 240ºC,
Yield 95%). The elemental analysis data are consistent with the formula of the compound. The compound
was also characterized by IR, UV-Vis, 1H, 13C NMR and mass spectral techniques.
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Scheme 1: Synthesis of BCBQI & BCBQII.
2.3 Physical Measurements
Analysis of carbon, hydrogen and nitrogen content of BCBQ was carried out on a Vario EL-III
CHN Elemental Analyzer at the SAIF, Cochin University of Science and Technology, India. Mass spectra
were recorded with JEOL GCMATE II GC-MS spectrometer with Electron Impact (EI) mode at SAIF,
IIT Madras, India. IR spectra were recorded on a Perkin Elmer Infrared Spectrometer using KBr pellets in
the range 4000-400 cm-1. Electronic spectra were recorded in CHCl3 solution on a Schimadzu UV-2450
1
UV-Visible Spectrophotometer. The H, 13C and 2D COSY NMR spectra were recorded using Bruker
DRX-MHz NMR Spectrometer with CDCl3 as solvent and TMS as the standard at the SAIF, IIT Madras,
India. SEM analysis was carried out using Nova Nano SEM 450 at 15.00kV at Department. of
Optoelectronics, University of Kerala. FT Raman spectra were recorded using BRUKER RFS 27 stand
alone FT-Raman spectrometer in the scan range 50-4000 cm-1 at SAIF, IIT Madras, India. DSC curves
were recorded with NETZSCH STA 449 F3 Jupiter DSC analyzer with a heating rate of 10ºC/
minute from 10ºC to 300ºC under nitrogen atmosphere at SAIF, IIT Madras, India.
2.4 X ray Crystallography
Single crystals of compounds BCBQI & BCBQII of X-ray diffraction quality were obtained from
refluxed methanol solution by slow evaporation at room temperature in air. The crystallographic data and
structure refinement parameters are given in Table 2. The data were collected using a Bruker AXS Kappa
Apex 2 CCD diffractometer, with graphite-monochromated Mo Kα (λ
= 0.71073Å) radiation. The unit cell
dimensions and intensity data were recorded at 296 K. The program SAINT/XPREP (BRUKER, 2004)
was used for data reduction and APEX2/SAINT (BRUKER, 2004) for cell refinement [26]. The structure
solution was done using SIR92 (27] and refinement was carried out by full-matrix least squares on F2
using SHELXL-97 [28]. All non-hydrogen atoms were refined with anisotropic thermal parameters. The
hydrogen atoms on nitrogen atoms were refined isotropically while those on carbon atoms were
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geometrically fixed and refined using riding model. Molecular graphics employed were DIAMOND
Version 3.1f [29], MERCURY [30] and PLATON [31].
3 Results and discussion
BCBQI and BCBQII are synthesized in good yield (95%) by refluxing methanolic solution of
vanillin (1.53 g, 10 mmol)/ ethyl vanillin (1.66 g, 10 mmol) with cyclohexylamine (1.98 g, 20 mmol) in
1:2 molar ratio in the presence of 6 drops of glacial acetic acid for 1 hr. Red needle shaped crystals of
BCBQI and red block shaped crystals of BCBQII were filtered, washed with methanol and dried. BCBQI
& BCBQII are found to be polymorphs. The asymmetric unit of BCBQI consist of a four molecules
which belongs to monoclinic space group P21/c while that of BCBQII consist of two molecules which is
triclinic and belong to space group P1. The stoichiometries of the compounds were assigned based on
elemental analysis data and are given in Table 1. Mass spectral data gives a molecular ion peak at m/z =
302 for both the polymorphs. The mass spectrum of the polymorphs are available in the supplimentary
data Fig S1 & S2.
Table 1: Elemental Analysis of BCBQI & BCBQII
Compound
BCBQI
C, found (calc)
71.65 (71.50)
71.68 (71.50)
H, found (calc)
8.62 (8.70)
N, found (calc)
9.19 (9.30)
BCBQII
8.60 (8.70)
9.21 (9.30)
3.1 Crystal structure of BCBQI & BCBQII
The molecular structure of BCBQI along with atom numbering scheme is given in Figure 1. The
compound crystallizes in a monoclinic space group P21/c. Unit cell of BCBQI consist of 4 molecules.
Selected bond lengths and bond angles of BCBQI are given in Table 2. The C(7)
bond lengths (1.236 Å & 1.234 Å) are very close to the formal C O bond length in p-benzoquinone
(1.225 Å) which confirms the presence of benzoquinone moiety in BCBQI. The slight elongation of C
bond is attributed to the hydrogen bonding network. The close proximity of C(9) N(2) and C(4) N(1)
̶ O(1) & C(15) ̶ O(2)
═
̶
O
̶
̶
bond lengths (1.448 Å & 1.456 Å) shows that the quinone ring is substituted by two cyclohexylamino
groups at 2 and 5 positions. All the bond angles (110.9º) and C-C bond lengths confirms the chair
conformation of cyclohexyl groups in BCBQI. The C(5)
̶ N1 & C(8) ̶ N(2) bond lengths (1.333 Å &
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1.336 Å) are intermediate of C
═N bond length (1.28 Å) and C ̶ N length (1.47 Å) which shows extended
π
delocalization of quinone ring.
BCBQII crystallizes in a triclinic point group P1. The molecular structure of BCBQII along with
atom numbering scheme is given in Figure 1. Selected bond lengths and bond angles of BCBQII are
given in Table 3. Even though the empirical formula and molecular weight of BCBQI and BCBQII are
the same, the unit cell of BCBQII consist of two molecules. Detailed analysis of bond lengths and bond
angles in BCBQII shows that two cyclohexyl amino rings in chair conformation are attached to the 2,5
positions in a para benzoquinone ring. Ring puckering analysis confirms the cyclohexyl C
lengths of the same magnitude in BCBQI & BCBQII.
̶ N bond
Fig 1: Molecular structures of BCBQI (left) & BCBQII (right).
Search for and analysis of solvent accessible voids in the crystal packing of BCBQII revealed a
potential solvent accessible volume of approximately 17.3 Å3 (844.8 Å3 per unit cell volume & 2.1% of the
total unit cell volume). BCBQII has 2 discrete molecules in its unit cell and the formation of even a
monohydrate needs void volume of 80 Å3 as a simple water molecule has a volume of about 40 Å3. Thus it is
clear that the crystal packing of BCBQII is solvent free as is the case of BCBQI which has no potential
solvent accessible voids. This confirms that BCBQI & BCBQII are pure polymorphs.
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Table 2: Selected bond lengths (Å) and bond angles (º) in BCBQI & BCBQII
BCBQI
BCBQII
Bond lengths
Bond lengths
C(1)
C(3)
C(4)
C(5)
C(5)
C(7)
C(15)
C(8)
C(17)
̶
C(2)
C(4)
N(1)
N(1)
C(6)
O(1)
C(4)
C(5)
C(6)
C(7)
C(7)
C(9)
C(18)
C(16)
C(15)
̶
C(5)
C(6)
N(1)
N(1)
C(8)
O(1)
O(2)
N(2)
N(2)
1.522(3)
1.512(3)
1.457(3)
1.332(2)
1.363(3)
1.236(2)
1.234(2)
1.337(2)
1.448(2)
1.521(3)
1.510(3)
1.457(2)
1.331(2)
1.371(2)
1.236(2)
1.231(2)
1.332(2)
1.448(2)
̶
̶
̶
̶
̶
̶
̶
̶
̶
̶
̶
O(2)
N(2)
N(2)
̶
̶
̶
̶
̶
Bond angles
Bond angles
C(2)
C(3)
C(4)
C(6)
C(16)
C(8)
̶
C(1)
C(4)
̶
C(13)
C(1)
̶
C(12)
̶
C(13)
C(14)
111.4(2)
110.67(18)
110.66(15)
126.16(16)
120.80(15)
124.28(17)
124.87(16)
̶
̶
C(14)
C(5)
C(10)
C(15)
C(17)
C(17)
̶
C(15)
̶
110.83(19)
124.88(18)
120.85(16)
123.65(19)
124.87(17)
̶
̶
N(1)
C(5)
̶
̶
̶
̶
N(2)
̶
C(16)
C(18b)
O(2)
̶
C(15)
C(16)
C(18)
̶
̶
̶
C(15)
̶ O(2)
̶
N(2) C(17)
̶
C(7) ̶ N(1) ̶ C(6)
Both inter and intramolecular hydrogen bonding exists in the crystal lattice of the polymorphs. Both
the oxygen atoms O(1) and O(2) form intramolecular hydrogen bonds of same bond length (2.62Å) with
N(2)H(2) & N(1)H(1) respectively in BCBQI. But in the case of BCBQII, intramolecular hydrogen bond
involving N(2)H(2)
bonds shows the reverse trend. i.e.in BCBQII, intermolecular hydrogen bonds with same bond length
(3.0Å) exist between N(2)H(2) O(1) and N(1)H(1) O(2) while in BCBQI, slightly longer bond (3.2Å) is
formed by N(2)H(2) O(1) than N(1)H(1) O(2) (2.9Å). Intermolecular hydrogen bonds with same
magnitude in BCBQII results in a regular packing diagram than in BCBQI. Existence of hydrogen
bonding is confirmed by IR spectra which shows a downward shift of C
O (stretching) from 1651cm-1
̶ O(2) is longer (2.62Å) than that with N(1)H(1) ̶ O(1) (2.36Å). The intermolecular H-
̶
̶
̶
̶
═
[32] to 1640cm-1 in BCBQI and to 1639cm-1 in BCBQII. Analysis of the donor-hydrogen and hydrogen-
acceptor distances shows that inter & intramolecular H-bonds in BCBQII is little bit stronger than that in
BCBQI which may be the reason for the difference in C═O stretching frequency. H- bonds of comparable
strength can also be seen between C(6) H(6) O(1) in the polymorphs. Bond angles of H-bonds are given
̶
̶
in Table 3. The packing diagram along with hydrogen bonding in the polymorphs are shown in Figure 2.
The crystal data and structure refinement parameters of the polymorphs are given in table 4.
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Table 3: H-bonds in BCBQI (top) and BCBQII (bottom)
D-H...A
d(D-H)(A0) d(H...A)(A0) d(D...A)(A0) <(DHA)(A0)
N(1)-H(1)...O(1)
0.878(19)
0.878(19)
0.877(17)
0.877(17)
0.98
2.401(18)
2.19(2)
2.19(2)
2.185(16)
2.5
3.201(2)
2.624(2)
2.621(2)
2.943(2)
3.436(2)
151.8(17)
109.8(17)
109.9(15)
144.5(16)
159
N(1)-H(1)...O(2) (Intra)
N(2)-H(2)...O(1) (Intra)
N(2)-H(2)...O(2)
C(6)-H(6)...O(1)
D-H...A
d(D-H)(A0) d(H...A)(A0) d(D...A)(A0) <(DHA)(A0)
N(1)-H(1)...O(2)
0.85(3)
0.85(3)
0.85(2)
0.85(2)
0.96(2)
2.43(2)
2.17(3)
2.36(2)
2.16(2)
2.45(2)
3.095(2)
2.362(2)
3.082(2)
2.622(2)
3.393(2)
135(2)
114(2)
N(1)-H(1)...O(1) (Intra)
N(2)-H(2)...O(2) (Intra)
N(2)-H(2)...O(1)
143(2)
113.8(18)
168.1(17)
C(6)-H(6)...O(1)
Fig 2: Packing diagram and H-bonding in BCBQI (left) & BCBQII (right)
A noticeable difference between the polymorphs lies in the existence of a CH-pi interaction in
BCBQII which is absent in BCBQI. This may be due to the close proximity of 6 membered benzoquinone
ring (Cg2) with C11
̶
H11 (2.93Å) which is shown in Fig 3.
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Fig 3: C-H Pi interaction in BCBQII
Fig 4: Crystals of BCBQI (left) & BCBQII (right)
Table 4: Crystal data and structure refinement parameters for BCBQI & BCBQII
BCBQI
BCBQII
Empirical formula
Formula weight
Temperature (K)
C18H26N2O2
302.41
296(2)
C18H26N2O2
302.41
296(2)
Wavelength (Ǻ)
Crystal system
Space Group
0.71073
Monoclinic
P21/c
0.71073
Triclinic
P1
Unit cell dimensions
a (Ǻ)
b (Ǻ)
14.1900(17)
8.9500(9)
6.5527(7)
11.3446(12)
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c (
Ǻ
)
13.3634(12)
90
12.7558(13)
68.681(8)
87.015(6)
Alpha (°)
Beta (°)
99.479(5)
Gamma (°)
Volume V ( Ǻ3
Z
90
73.326(6)
844.76(16)
2
)
1674.0(3)
4
Dcalc (mg/m3)
1.2
1.189
Absorption coefficient,µ (mm-1)
0.078
0.078
F(000)
656
328
Crystal size (mm)
0.50x0.20x0.20
0.350 x 0.300 x 0.300
Theta range for data collection (°)
1.45-28.40
3.085 - 28.313
Limiting indices
-18
≤
k
h
≤
≤
18
11
17
-5 ≤ h ≤ 8
-9
≤
-13
-16
≤
k
≤
15
16
-16
≤
l
≤
≤ l ≤
Reflections collected
13027
4069
Independent Reflections (Rint)
4196(0.0335)
28.40º (99.3%)
4069 (0.0199)
Completeness to theta
25.242 º (98.8 %)
Absorption correction
Semi-empirical from equivalents
Maximum and Minimum Transmission
Refinement method
0.9845 and 0.9619
0.9751 and 0.9554
Full-matrix least-squares on F^2
Data / restraints / parameters
Goodness-of-fit on F^2
4164 / 0 / 200
1.036
4206 / 0 / 215
0.991
Final R indices [I>2sigma(I)]
R1 = 0.0583
wR2 = 0.1776
R1 = 0.1046
wR2 = 0.2162
0.251 and -0.185
0.0568
0.1529
R indices (all data)
0.0873
0.1745
0.187 and -0.198
Largest diff. peak and hole ( e.Å-3)
3.2 IR spectra
The FTIR spectra of BCBQI and BCBQII are shown in Fig 6. A strong band at 2852cm-1
corresponds to sp3C
H (stretching) in cyclohexyl group which shows the presence of two substituted
cyclohexyl rings in BCBQI. The N H (stretching) vibration in a secondary amine is characterized by a
strong band at 3271cm-1which proves the presence of two secondary amino groups in BCBQI. The
shifting of N H stretching vibration towards low wave number is attributed to the presence of H-bonding
in the form of N
ꢀꢀꢀO [33]. A strong band at 1640cm-1 is characteristic of keto group in p-benzoquinone
̶
̶
̶
̶
H
which shows a downward shift which may be due to the hydrogen bonding. C═C (stretching) band at
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1563cm-1 confirms the benzoquinone moiety in BCBQI. The electronic spectral data also supports the
presence of a quinone ring involved in hydrogen bonding in BCBQI and BCBQII. The assignments for
some selected frequencies are summarized in Table 5.
The polymorph BCBQII shows almost similar absorption frequencies. sp3C
cyclohexyl group appears at 2853 cm-1 and a strong peak at 3269 cm-1 corresponds to N
vibration. The C ═O
C (stretching) peak of benzoquinone moiety in BCBQII appears at 1562 cm-1. The C
̶
H (stretching) in
H (stretching)
̶
═
stretching vibration occurs at 1639 cm-1 which shows a slight downward shift which may be due to the
hydrogen bonding network.
The slight difference in frequencies for the polymorphs is evident from the table. The spectra of
the polymorphs appear almost identical. The differences in intermolecular and lattice vibrations due to the
different ordering in the crystal lattice are responsible for variations within the spectra. Density functional
studies has also been carried out for structure and vibrational spectra of transient intermediates of p-
benzoquinone[34]. Nonella et al has studied the IR spectrum of p-benzoquinone in water obtained from
QM/MM hybrid molecular dynamic simulation[35].
Table 5: IR assignments in BCBQI and BCBQII
Wavenumber(cm-1)
Assignment
BCBQI
1640
BCBQII
1639
ʋC
ʋC
ʋC
ʋN
ʋC
═
O(Stretching)
C(Stretching)
═
1563
2852
1562
2853
̶
̶
H(Stretching) Cyclohexyl
H(Stretching) 20 amine
N ( Stretching)
3270
1091
3269
1088
̶
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BCBQI
BCBQII
100
80
60
40
20
0
100
80
60
40
2852cm -1
2 853cm -1
1640 cm- 1
1639 cm-1
3270cm-1
3269cm-1
20
1563cm-1
1562cm-1
0
4000
3500
3000
2500
2000
1500
)
1000
500
4000
3500
3000
2500
2000
1500
1000
500
Wavenumber(cm-1
Wavenumber(cm-1
)
Fig 5: FTIR spectra of BCBQI (left) & BCBQII (right)
3.3 FT Raman spectra
Raman spectroscopy being a vibrational spectroscopic technique, yields important information
which is related to the geometric structure of a molecule and its environment. Changes in crystal packing
geometries cause band shifts or changes in relative intensity. FT Raman spectrum of the polymorphs were
recorded on a Bruker RFS 27 stand alone spectrophotometer with 50-4000 cm-1 scan range and 2 cm-1
resolution. The C
The C
C stretching frequencies at 1592 cm-1 & 1517 cm-1 appears to be similar in the polymorphs. The
CH2 peak at 1142 cm-1 also shows similarity. The C N inplane bending absorption appears at 440 cm-1
CH2 antisymmetric stretching frequencies of cyclohexyl rings appear at 2931cm-1 in both the
̶
H stretching vibration in BCBQI is at 3066 cm-1 while it is at 3064cm-1 in BCBQII.
═
δ
̶
while
β
polymorphs. An additional absorption frequency at 971cm-1 in BCBQII is due to the ring puckering which
is absent in BCBQI. Similarly BCBQII gives an absorption at 847 cm-1 due to
CH2 wagging and 554
cm-1 due to CH2 wagging which are absent in BCBQI. Few more additional peaks at 695 cm-1, 309 cm-1
γ
β
& 269 cm-1 appear in the spectrum of BCBQII which may be due to the different crystalline nature of the
polymorphs. The Raman spectra of the two polymorphs are given in Fig 6.
Fig 6: FT Raman spectra of BCBQI (left) & BCBQII (right)
12

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3.4 Electronic Spectra
The UV-Visible spectra of the polymorphs were taken on a Varian, Carry 5000
spectrophotometer in CHCl3.The electronic spectrum of unsubstituted parabenzoquinone is characterized
by an n→π* transition at 439nm and an allowed and forbidden π→π* transitions at 240nm and 288nm
[36]. The presence two cyclohexylamino substituents produces a bathochromic shift of n→π*transition to
445nm and π→π* transitions to 306nm and 395nm in BCBQI. While in the polymorph BCBQII, n→π
*
*
transition appears at 453nm and π→π* transitions at 305nm & 390nm. The weak nature of n→π
transitions compared to π →π* may be due to the existence of H-bonding network which provides a stiff
structure and prevents the rotation of cyclohexylamino group around C N bond. This will prevent the n
̶
orbit on nitrogen atom in overlapping with pi orbital on quinone ring to make n→π* transition.
Theoretical interpretations of the electronic bands of 1,4-benzoquinones [37,38] and its derivatives has
also been carried out by various methods[39,40].
305nm
306nm
1.2
1.0
0.8
0.6
0.4
0.2
1.2
1.0
0.8
0.6
0.4
0.2
BCBQII
BCBQI
445nm
453nm
390nm
395nm
300
400
500
600
700
800
300
400
500
600
700
800
Wavelength(nm)
Wave length (nm)
Fig 7: Electronic Spectra of BCBQI and BCBQII
3.5 1H NMR spectra
1H and 13C NMR spectra of the title compounds were recorded in CDCl3 on Bruker Avance III,
1
400MHz spectrometer. H NMR: CDCl3, 400MHz, ppm. A doublet at 6.606 ppm in the spectrum of
BCBQI corresponds to the vinylic protons in the benzoquinone moiety. A singlet at 5.330 ppm indicates
the two protons on nitrogen atom which is shifted up field due to intramolecular hydrogen bonding
between N1(H1) ̶ O2 & N2(H2) ̶ O1 is evident from the crystal structure. A multiplet at 3.2 ppm
represents the two protons on cyclohexyl ring carbon attached to nitrogen atom. 8 hydrogen atoms (axial
& equatorial) on C (17), C (10), C (3) & C (14) forms a multiplet at 1.7 ppm. Four axial protons on C (2),
13

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C (11), C (10) & C (13) forms a multiplet at 1.6 ppm whereas the corresponding equatorial protons form a
multiplet at 1.3 ppm. Axial and equatorial protons on C (1) & C (12) forms a multiplet at 1.28 & 1.21
ppm.
Even though certain resonance peaks can be observed at identical chemical shifts, the NMR
spectra of the polymorphs contain nonequivalent resonance peaks. This effect arises due to the different
crystal structures of the polymorphs which results in shifting of certain resonance peaks in the spectrum.
The vinylic protons in benzoquinone moiety of BCQII forms a doublet at 1.606 ppm just like BCBQI.
The singlet peak at 5.329 ppm corresponds to hydrogen bonded N1 (H1) and N2 (H2) which is slightly
shifted from the corresponding peak in BCBQI. The H (6) & H(15) forms a sharp singlet at 3.256 ppm in
place of the multiplet in BCBQI. The multiplet at 1.7 ppm in BCBQI is replaced by a doublet in BCBQII
which again confirms the polymorphic behavior of BCBQI & BCBQII.
The COSY spectra were used to identify coupled spin systems in the molecule as well as spins
that were adjacent within a given spin system. The off diagonal spots at 6.6 ppm & 3.2 ppm in the COSY
spectra shows the correlation between vinylic proton in benzoquinone moiety [C(16) & C(6) in BCBQI
and C(8) & C(17) in BCBQII] with proton on cyclohexyl ring carbon attached to nitrogen atom. Off
diagonal correlation spots at 1.3 ppm & 3.2 ppm also shows the coupling between cyclohexyl proton
present on carbon attached to nitrogen with those ortho to the same carbon atom. The proton present in
nitrogen atom does not give any cross peaks which shows that it does not involve in coupling with
adjacent protons. Similar is the case of protons at 1.6 ppm & 1.7 ppm.
3.6 13C NMR spectrum
The 13C NMR spectrum provides direct information about the carbon skeleton as given in Table8.
There are seven unique carbon atoms in the molecule which gives a total of 7 peaks in the spectrum. C(7)
and C(15) carbon atoms of benzoquinone ring gives a singlet at 178.02 ppm which shows an up field shift
due to the presence of a nitrogen atom with lone pair of electrons. C(6),C(5) & C(8),C(16) of
benzoquinone moiety also show an up field shift and gives a peak at 92.69 ppm. Carbon atoms present in
cyclohexyl rings can also be clearly distinguished from the peaks. The 13C spectra acquired for
polymorphs BCBQI and BCBQII show distinct 13C resonance shifts from each other which is evident
from Table 6.
14

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Table 6: 13CNMR assignments of BCBQI & BCBQII (ppm)
BCBQI
Chemical shift BCBQII
Chemical shift
178
C(7) & C(15)
178
150
93
C(9) & C(18)
C(5) & C(8)
C(7) & C(16)
150
C(6) & C(16)
C(8) & C(17)
93
C(4) & C(9)
51
C(6) & C(15)
51
C(3), C(10),C(14), C(17)
C(1) & C(12)
32
C(1),C(5), C(10),C(14)
C(3) & C(12)
31.99 &31.67
25.37 & 25.23
24.61 &24.48
25
C(2), C(11), C(13), C(18)
24
C(2),C(4),C(11),C(13)
3.7 Field Emission Scanning Electron Microscopic analysis of polymorphs
Scanning electron microscopy being superior to optical microscopy finds application in
the discrimination of polymorphs. SEM generates high-resolution images and precisely measures
very small features and objects. The external morphology of the polymorphs can clearly be
identified by SEM images [41]. The needle type and block type morphology of BCBQI &
BCBQII can clearly be distinguished by 1000× magnified images shown in Figure 8.
Fig 8: A 1000× magnified FESEM images of BCBQI (left) & BCBQII (right)
A 25,000× magnified image shows a layer like structure for BCBQII. The morphology as
well as magnified images of the polymorphs are shown in Figure 9 which clearly distinguishes
both.
15

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Fig 9: A 25,000× magnified images of BCBQI (left) & BCBQII
3.8 Thermal analysis of the polymorphs
On heating BCBQI and BCBQII on a watch glass on a hot plate, block shaped BCBQII
started to change its appearance followed by melting. This shows that BCBQII undergo some
kind of solid-solid transition before melting which is confirmed by the differential scanning
calorimetric analysis of the polymorphs. Being a thermo mechanical analysis, DSC provides
useful information for the identification and confirmation of polymorphs. DSC analysis was
performed from 10ºC to 300ºC at a heating rate of 10ºC/ minute under nitrogen atmosphere on a
NETZSCH STA 449 F3 Jupiter DSC instrument. The DSC of BCBQII shows two thermal
events: a small exothermic event at 183.5ºC which represents the solid-solid phase transition and
sharp endothermic event at 240ºC which is the melting point of BCBQII and BCBQI. Thus DSC
provides a clear distinction between the two polymorphs with 183.5ºC as the transition
temperature between the two and 240ºC as their melting point as shown in figure 10.
1
183.5oC
BCBQII
BCBQI
0
-1
-2
-3
-4
-5
0
-1
-2
-3
-4
-5
-6
240oC
240oC
50
100
150
200
250
300
200
210
220
230
240
250
260
Temperature (°C)
Temperature (°C)
Fig 10: DSC Curves of BCBQI (left) & BCBQII (right)
16

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3.9 Proposed mechanism
We suggest that the mechanism shown in Fig 11 may be operative. The photo oxidation of
cyclohexylamine in methanol medium can give an adduct cyclohexylamine hydro peroxide [42]. Dakin
oxidation can convert hydroxy benzaldehydes to benzoquinones using H2O2/base. Here cyclohexylamine
hydro peroxide may play the role of H2O2/base just like urea-H2O2 adduct [43]. CHA adduct may add to
carbonyl carbon atom and reaction proceeds like Dakin reaction. Resulting 2-ethoxy-1, 4-benzoquinone
undergoes nucleophilic substitution by cyclohexylamine to give BCBQI & BCBQII. Primary amines may
reversibly form imines with quinones, but the isolatable products are the less labile quinone substitution
products [44].
Fig 11: Proposed mechanism of formation of BCBQI& BCBQII
17

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Conclusion
The flavoring agents, vanillin and ethyl vanillin have been converted into 2,5-
bis(cyclohexylamino)-1,4-benzoquinone polymorphs which find application in dye industry.
Cyclohexylamine acts both as an oxidizer for vanillins and as a nucleophile for intermediate p-
benzoquinone. The whole reaction occurs in a single pot taking only 1 hr refluxing time. Bright red
crystals of BCBQI & BCBQII which are polymorphs showing difference only in crystal structure were
characterized and distinguished spectroscopically and by single crystal X-ray diffraction. A possible
mechanism has also been suggested.
Acknowledgements
One of the authors A.Asha, acknowledges University Grants Commission (UGC), Government.
Of India for financial assistance under the Faculty Development Programme (FDP) and A. Sheena Mohan
to Govt. of Kerala for providing her scholarship.
Appendix A: Supplimentary Material
CCDC 1531838 and 1531839 contain the supplimentary 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.
18

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•
•
•
Two polymorphs of 2,5-bis(cyclohexylamino)-1,4-benzoquinone are synthesized from
methyl/ethyl protocatechuic aldehydes and cyclohexylamine.
A mechanism involving oxidation of aromatic aldehydes by generated aminehydroperoxide to
benzoquinone moiety followed by its nucleophilic substitution has been proposed.
The synthesized polymorphs belonging to different crystal systems are characterized and
distinguished by Single Crystal XRD, FTIR, FTRAMAN, NMR, FESEM and DSC analysis.