Synthesis, crystal structure and ab initio studies of cyclohexyl n-phenylcarbamate

Article abstract of DOI:10.1007/s10870-010-9812-9

Cyclohexyl N-phenylcarbamate, C₁₃H₁₇NO₂ (I), which is a useful target for biotransformations by fungi, has been synthesized and the structure has been solved by X-ray diffraction. The crystals are triclinic, space group P

Full text of DOI:10.1007/s10870-010-9812-9

J Chem Crystallogr (2010) 40:1150–1154
DOI 10.1007/s10870-010-9812-9
ORIGINAL PAPER
Synthesis, Crystal Structure and ab initio Studies of Cyclohexyl
N-Phenylcarbamate
•
P. S. Pereira Silva Raza Murad Ghalib
•
•
Sayed Hasan Mehdi Rokiah Hashim
•
•
Othman Sulaiman Ali Jawad
Received: 21 January 2010 / Accepted: 21 May 2010 / Published online: 5 June 2010
Ó Springer Science+Business Media, LLC 2010
Abstract Cyclohexyl N-phenylcarbamate, C13H17NO2
(I), which is a useful target for biotransformations by fungi,
has been synthesized and the structure has been solved by
X-ray diffraction. The crystals are triclinic, space group P
Introduction
Carbamates are a well known class of compounds which
can be prepared by different methods, for example car-
bonylation of aromatic nitro compounds [1], by the reac-
tion of isocyanates with alcohols and by the reaction of an
amine and an alcohol with phosgene. Previous investiga-
tions also report the synthesis of cyclohexyl N-phenylcar-
bamate by the reaction of cyclohexanol and formanilide in
the presence of a catalytic amount of RuCl2(PPh3)3 [2].
Here the title compound has been synthesized by the
reaction of cyclohexanol and phenylisocyanate in the
presence of a catalytic amount of HCl (see Scheme 1 and
‘‘Experimental’’ section for details). Like the synthesis by
Kotachi et al. [2], our synthesis avoids the use of highly
toxic and corrosive phosgene and does not require a poi-
sonous carbon monoxide atmosphere.
ꢀ
˚
1, with a = 5.2581 (2) A, b = 9.5080 (3) A, c = 12.6165
˚
˚
(4) A, a = 70.544 (2)°, b = 89.075 (2)°, c = 80.447 (2)°,
3
Mr = 219.28, V = 585.96 (3) A , Z = 2 and R = 0.065. In
˚
the title compound the phenyl ring makes a dihedral angle
of 30.68(7)° with the carbamate group The molecules are
linked into infinite chains via N–HÁÁÁO hydrogen bonds
along the a axis. These hydrogen-bonded chains are further
linked by weaker C–HÁÁÁp interactions. Quantum-mechan-
ical ab initio calculations for the free molecule reproduce
well the observed bond lengths and valency angles but
show that the crystal packing might be responsible for the
rotation of the phenyl ring out of the carbamate plane in the
solid state conformation.
N-Phenylcarbamates of cyclic alcohols are useful targets
for biotransformations by fungi [3, 4], namely the micro-
biological hydroxylation of chemically non-activated
hydrocarbon positions involving monooxygenases. Based
on earlier knowledge and new results of hydroxylation of
N-Phenylcarbamates with the fungus Beauveria bassiana
ATCC 7159, Pietz et al. [5] proposed a modification of the
distance-models by Fonken et al. [6] and Fourneron et al.
[7], to exclude distance variations caused by the mobility
of the phenylcarbamate function. According to the model
by Pietz et al., the regio- and stereochemistry of hydrox-
ylation is determined mainly by the structure of the
hydrocarbon moiety, namely by a specific distance from
the group that anchors to the enzyme. This corresponds to
Keywords Crystal structure Á Synthesis Á
Cyclohexyl N-phenylcarbamate Á Ab initio calculations
P. S. Pereira Silva (&)
CEMDRX Physics Department, University of Coimbra,
3004-516 Coimbra, Portugal
e-mail: psidonio@pollux.fis.uc.pt
R. M. Ghalib Á S. H. Mehdi Á R. Hashim Á O. Sulaiman
School of Industrial Technology, Universiti Sains Malaysia,
11800 Pulau Pinang, Malaysia
˚
an optimum distance of 5.5 A between the oxygen atom
directly attached to the carbocyclic part of the substrate and
the substituted H atoms. In order to gain insight into the
sterical requirements for the substrates of the enzymatic
A. Jawad
Department of Physics, AMU, Aligarh, UP 202002, India
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J Chem Crystallogr (2010) 40:1150–1154
1151
system it is essential to obtain exact information on its
structures. The title compound, provides a good model
substrate for studying the selective oxygenation of non-
activated positions by microorganisms.
Table 1 Crystallographicdataandstructurerefinementofcompound(I)
Empirical formula
C13H17NO2
Formula weight
Temperature (K)
219.28
293(2)
In this work, we report the synthesis and the crystal
structure of (I), as determined by single-crystal X-ray
analysis. To investigate the effect of the intermolecular
interactions in the conformation of the molecule we have
performed the optimization of the geometry of the isolated
molecule using Hartree–Fock (HF) and density functional
theory (DFT) calculations.
˚
Wavelength (A)
0.71073
Triclinic
Crystal system
Space group
ꢀ
P 1
˚
a (A)
5.2581(2)
9.5080(3)
12.6165(4)
70.544(2)
89.075(2)
80.447(2)
585.96(3)
2
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
Experimental and Computational Methods
3
˚
Volume (A )
Preparation of the Title Compound
Z
Calculated density (g/cm3)
1.243
A mixture of cyclohexanol (1.04 mL, 10 mmol) and
Phenylisocyanate (1.08 mL, 10 mmol) in molar ratio 1:1
were stirred in chloroform for 30 min by drop wise addi-
tion of a catalytic amount of HCl (see Scheme 1). The
reaction mixture was filtered and dried at low pressure on
rota-vapour. The dried mass was crystallized with solvent
system diethyl ether and hexane to give colourless and
transparent single crystals (melting point: 357–358 K) of
the title compound (1.95 g). The melting point was deter-
mined on a Kofler block melting point apparatus and is
uncorrected.
Absorption coefficient
(mm-1
F(000)
0.084
)
236
Crystal size (mm)
0.26 9 0.22 9 0.12
1.71–27.64
h range for data collection (°)
Index ranges
-6 \ h \ 6, -12 \ k \ 12,
-16 \ l \ 15
11966/2690 [R(int) = 0.0350]
Reflections collected/unique
Completeness to h = 25.008
Refinement method
99.9%
Full-matrix least-squares on F2
2690/0/145
Data/restraints/parameters
Goodness-of-fit on F2
1.080
Crystal Structure Determination
Final R indices [I [ 2r(I)]
R indices (all data)
R1 = 0.0653, wR2 = 0.1309
R1 = 0.0993, wR2 = 0.1446
0.176 and -0.215
A crystal of (I) with a thick plate shape and having
approximate dimensions of 0.26 mm 9 0.22 mm 9
0.12 mm was glued on a glass fibre and mounted on a
Bruker Apex II diffractometer. Diffraction data were col-
lected at room temperature 293(2) K using graphite
Largest diff. peak and hole
-3
˚
(e A
)
˚
difference Fourier synthesis, placed at calculated positions
and then, included in the structure factor calculation in a
riding model using SHELXL-97 defaults. The final least-
squares cycle was based on 2690 observed reflections
[I [ 2r(I)], 145 variable parameters, converged with
R = 0.0653 and wR = 0.1309. Additional information to
the structure determination are given in Table 1. Selected
structural parameters can be seen in Table 2. Supplemen-
tary data have been deposited at the Cambridge Crystal-
lographic Data Centre (CCDC No. 761451).
monochromated Mo Ka (k = 0.71073 A). Data reduction
was performed with APEX II [8]. Lorentz and polarization
corrections were applied. Absorption correction was
applied using SADABS [9]. The crystallographic structure
was solved by direct methods (SHELXS-97) [10]. Refine-
ments were carried out with SHELXL-97 package [10]. All
refinements were made by full-matrix least-squares on F2,
with anisotropic displacement parameters for all non-
hydrogen atoms. All the hydrogen atoms were located in a
Ab Initio Calculations
The geometry optimizations were performed using the PC
GAMESS/Firefly QC package [11], which is partially
based on the GAMESS (US) source code [12], starting
from the experimental X-ray geometry. We performed two
Scheme 1 Route of synthesis of (I)
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J Chem Crystallogr (2010) 40:1150–1154
Table 2 Comparison of selected geometrical parameters for (I) as
determined by X-ray diffraction and from DFT and HF calculations
˚
(A, °)
Experimental
DFT
1.360
HF
O1–C7
1.340 (2)
1.461 (2)
1.327
1.433
1.195
1.357
1.406
O1–C1
1.452
1.217
O7–C7
1.208 (2)
N8–C7
1.354 (2)
1.373
Fig. 1 ORTEP diagram of the title compound with the ellipsoids
drawn at the 50% probability level, with the atomic labelling scheme
N8–C8
1.413 (3)
1.408
C7–O1–C1
C7–N8–C8
O1–C1–C2
O1–C1–C6
O7–C7–O1
O7–C7–N8
O1–C7–N8
C13–C8–N8
C9–C8–N8
C7–O1–C1–C2
C7–O1–C1–C6
C1–O1–C7–O7
C1–O1–C7–N8
C8–N8–C7–O7
C8–N8–C7–O1
C7–N8–C8–C13
C7–N8–C8–C9
115.75 (14)
125.82 (16)
107.31 (15)
109.48 (16)
124.76 (18)
125.44 (19)
109.79 (16)
118.31 (17)
122.29 (18)
-157.13 (17)
80.6 (2)
116.45
128.51
106.81
110.43
124.99
126.78
108.23
117.16
123.34
-152.84
85.06
118.50
128.73
106.59
110.38
124.47
126.47
109.05
116.81
123.85
-154.33
84.05
the central carbamate group. The phenyl ring is also
twisted about the carbamate group with a dihedral angle of
30.68(7)°. The geometry of the carbamate group is planar
as expected.
The molecules are linked in infinite chains running
parallel to the a axis, via hydrogen bonds involving the NH
groups and the carbonyl oxygen atom [Fig. 2; N8ÁÁÁO7i:
i
˚
3.072(2) A; N8–H8ÁÁÁO7 : 154°; symmetry code: (i) x - 1,
y, z]. This chains have a periodicity of four atoms, graph-
set symbol C(4) according to Etter’s graph-set theory [17,
18]. The same hydrogen-bonding motif has also been found
in other similar compounds [19, 20].
12.3 (3)
0.77
0.57
-167.71 (16)
-5.7 (3)
-179.40
-0.07
-179.89
-179.84
0.19
-179.63
-0.15
The molecular packing is also influenced by several
C–HÁÁÁp interactions between hydrogen atoms (H1, H2A,
H3B, H4A, H5B) of the cyclohexyl ring from one molecule
and the phenyl ring of symmetry related molecules. The
strongest C–HÁÁÁp interaction is of the type III as described
174.38 (17)
154.96 (19)
-28.3 (3)
-179.95
-179.48
0.44
i
˚
by Malone et al. [21], with a HÁÁÁp distance of 2.88 A, and
calculations, one with the molecular orbital HF method and
the other within DFT using B3LYP (Becke three-parameter
Lee–Yang–Parr) for exchange and correlation, which
combines the hybrid exchange functional of Becke [13, 14]
with the correlation functional of Lee et al. [15]. Both
calculations were performed with an extended 6–31G(d,p)
basis set. Tight conditions for convergence of both the self-
consistent field cycles and the maximum density and
energy gradient variations were imposed (10-5 atomic
units) in both calculations. At the end of these geometry
optimizations we conducted Hessian calculations to guar-
antee that the final structures correspond to true minima,
using the same level of theory as in the geometry
optimizations.
a C–HÁÁÁp angle of 146° [Fig. 3; symmetry code: (i) 1 - x,
Results and Discussion
ꢀ
Compound (I) crystallizes in the space group P 1 with one
molecule in the asymmetric unit (Fig. 1). The cyclohexyl
ring adopts a chair conformation, as shown by the Cremer
˚
and Pople [16] parameters [Q = 0.559(3) A, h = 0.9(3)°,
u = 281(16)°], and the basal plane (C2/C3/C5/C6) of this
ring makes a dihedral angle of 58.60(8)° with the plane of
Fig. 2 Packing diagram of compound (I), with the H-bonds shown as
dashed lines
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J Chem Crystallogr (2010) 40:1150–1154
1153
Fig. 3 Projection of the
packing diagram of (I) along the
a axis, showing the two
strongest C–HÁÁÁp interactions
as dashed lines. Symmetry
codes of the ring centroids: Cg1:
1 - x, 1 - y, 1 - z; Cg2:
1 - x, -y, 1 - z
1 - y, 1 - z]; H2A is above the centre of the aromatic ring
C8–C13 but the C2–H2A bond points towards the ring
edge. In the other relevant C–HÁÁÁp interaction, the C–H4A
bond points away from the ring but the hydrogen is close to
a carbon. This interaction is of the type VI according to the
classification of Malone et al. [21], with a HÁÁÁpii distance
We have performed a DFT calculation, using the method
described above, to determine the energy difference asso-
ciated with the rotation of the phenyl ring from the original
position (molecule with the solid-state conformation) onto
the carbamate plane, keeping the rest of the molecular
geometry constant and without relaxing the molecular
geometry. The value obtained, 0.76 kcal/mol (with the
planar conformation being more stable), is very small and
can be compared with the interaction energies of several
C–HÁÁÁp complexes calculated by Tsuzuki et al. [22],
ranging from -1.45 to -5.64 kcal/mol. This indicates that
the C–HÁÁÁp interaction may be responsible for the rotation
of the phenyl ring out of the carbamate plane.
˚
of 3.39 A, and a C–HÁÁÁp angle of 123° [Fig. 3; symmetry
code: (ii) 1 - x, -y, 1 - z]. These interactions, between
cyclohexyl and phenyl rings, bond molecules belonging to
different hydrogen-bonded chains.
In order to gain some insight on the influence of the
intermolecular interactions on the molecular geometry,
namely the relative orientation of the rings and the distance
between the ester oxygen and the H atoms at potential
hydroxylation positions, we have performed quantum
mechanical calculations of the equilibrium geometry of the
free molecule. The ab initio calculations reproduce well the
observed experimental bond lengths and valency angles of
the molecule but some of the calculated dihedral angles in
the free molecule differ significantly from those of the
molecule in the crystal (Table 2). The differences between
the calculated and experimental bond lengths are smaller
According to the criterion defined by Pietz et al. [5], the
hydrogen atom that can be potentially hydroxylated in
compound (I) is H4B. The distance between this hydrogen
and the oxygen directly attached to the carbocycle is very
stable despite the molecular flexibility of (I) [O1ÁÁÁH4B:
˚
˚
˚
5.141 A (crystal); 5.312 A (DFT); 5.272 A (HF)], con-
firming the usefulness of the model by Pietz et al.
Overall, our data suggest that the supramolecular
aggregation plays an important role in stabilizing the
observed geometry of (I).
˚
than 0.0266 and 0.0283 A, for the DFT and the HF cal-
culations, respectively. The largest disagreement between
the experimental and calculated angle values correspond to
the angle C7–N8–C8, which has a considerably smaller
value in the crystal. This may be explained by the partic-
ipation of the N8 atom in a hydrogen bond. The calcula-
tions show a reasonable agreement with the experimental
value for the dihedral angle between the least-square plane
of the carbamate group and the basal plane of the cyclo-
hexyl ring (DFT = 56.16° and HF = 54.79°). However,
both calculations predict that, in the free molecule, the
phenyl ring is almost coplanar with the carbamate group.
Supplementary Material
Crystallographic data for structural analysis have been
deposited with the Cambridge Crystallographic Data Cen-
ter, CCDC 761451. Copies of this information may be
obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (fax: ?44 1223 336 033;
e-mail: deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.
ac.uk).
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J Chem Crystallogr (2010) 40:1150–1154
Acknowledgments The first two authors contributed equally to this
work. We would like to acknowledge Universiti Sains Malaysia
(USM) for the University Grant 1001/PTEKIND/8140152 and Post-
doctoral Fellowship to Dr. Raza Murad Ghalib and Dr. Sayed Hasan
Mehdi. P. S. Pereira Silva acknowledges the support by Fundac¸a˜o
9. Sheldrick GM (2003) SADABS. University of Go¨ttingen,
Germany
10. Sheldrick GM (2008) Acta Crystallogr A64:112
11. Granovsky AA (2009) PC GAMESS/Firefly version 7.1.F.
http://www.classic.chem.msu.su/gran/gamess/index.html
12. Schmidt MW, Baldrige KK, Boatz JA, Elbert ST, Gordon MS,
Jensen JJ, Koseki S, Matsunaga N, Nguyen KA, Sue S, Windus
TL, Dupuis M, Montgomery JA (1993) J Comput Chem 14:1347
13. Becke AD (1988) Phys Rev A 38:3098
ˆ
para a Ciencia e a Tecnologia, under the scholarship SFRH/BD/
38387/2008.
14. Becke AD (1993) J Chem Phys 98:5648
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