Hydrogen-bonded chains in racemic 2-benzyl-3-(2-bromophenyl)propiononitrile and hydrogen-bonded sheets in methyl 2-benzyl-2-cyano-3-phenyl-propionate

Article abstract of DOI:10.1107/S0108270106032689

The molecules of 2-benzyl-3-(2-bromophenyl)propiononitrile, C ₁₆H₁₄BrN, are linked into chains by a single C-H...N hydrogen bond. The molecules of methyl 2-benzyl-2-cyano-3-phenylpropionate, C₁₈H₁₇NO₂, are linked into sheets by a combination of C-H...O and C-H...π(arene) hydrogen bonds.

Full text of DOI:10.1107/S0108270106032689

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
In (I) (Fig. 1), atom C2 is a stereogenic centre and the
molecules are chiral. The compound is racemic, and the
centrosymmetric space group P21/n accommodates equal
numbers of the R and S enantiomers; the selected reference
molecule has R con®guration. In addition, the skeletal
conformation does not exhibit even approximate symmetry, as
shown by the leading torsion angles, particularly those around
the C1ÐC17 and C2ÐC27 bonds (Table 1). By contrast, the
conformation adopted by the molecule of (II) (Fig. 2), where
there are no stereogenic centres, has approximate mirror
symmetry (Table 3), but the modest deviations from exact
symmetry are suf®cient to render the molecules chiral. The
chirality is a consequence only of the conformation in the solid
state but, in the absence of inversion twinning, each crystal of
(II) contains only a single enantiomer. In both compounds, the
C1ÐC2 bonds are very long, as is characteristic of nitriles
(Allen et al., 1987), with short C1ÐN1 bonds; the remaining
bond lengths and angles present no unusual features.
ISSN 0108-2701
Hydrogen-bonded chains in racemic
2-benzyl-3-(2-bromophenyl)propiono-
nitrile and hydrogen-bonded sheets in
methyl 2-benzyl-2-cyano-3-phenyl-
propionate
a
a
Â
Â
Guillermo Calderon, Luz Marina Jaramillo-Gomez,
b
b
c
Â
Jose M. de la Torre, Justo Cobo, John N. Low and
Christopher Glidewelld*
a
Â
Departamento de Quõmica, Universidad de Valle, AA 25360 Cali, Colombia,
b
Â
Â
Â
Â
Departamento de Quõmica Inorganica y Organica, Universidad de Jaen, 23071
Jaen, Spain, cDepartment of Chemistry, University of Aberdeen, Meston Walk, Old
Â
Aberdeen AB24 3UE, Scotland, and dSchool of Chemistry, University of St Andrews,
Fife KY16 9ST, Scotland
Correspondence e-mail: cg@st-andrews.ac.uk
Received 8 August 2006
Accepted 16 August 2006
Online 31 August 2006
The molecules of 2-benzyl-3-(2-bromophenyl)propiononitrile,
C16H14BrN, are linked into chains by a single CÐHÁ Á ÁN
hydrogen bond. The molecules of methyl 2-benzyl-2-cyano-3-
phenylpropionate, C18H17NO2, are linked into sheets by a
combination of CÐHÁ Á ÁO and CÐHÁ Á Áꢀ(arene) hydrogen
bonds.
Comment
The synthesis of heterocyclic systems containing pyrrolidine
fragments is an important goal because of the widespread
occurrence of such systems both in biologically active natural
products and in therapeutic agents. We present here the
molecular and supramolecular structures of two compounds
prepared for use as intermediates in the synthesis of pyrroli-
dines using radical cyclization methodology. 2-Benzyl-3-(2-
bromophenyl)propiononitrile, (I), was obtained in three steps
(see scheme) through successive alkylation of methyl 2-cyano-
acetate with benzyl chloride and potassium carbonate to give
the intermediate ester (III), and then with 2-bromobenzyl
bromide and potassium tert-butoxide to give (IV), followed by
controlled hydrolysis and decarboxylation of the resulting
cyano ester. By contrast, when potassium tert-butoxide was
employed as the base in the ®rst alkylation step, this gave a
double alkylation leading directly to methyl 2-benzyl-2-cyano-
3-phenylpropionate, (II). These two closely related nitriles
(Figs. 1 and 2), each containing two benzyl substituents, have
supramolecular structures that exhibit different types of
hydrogen bonding leading to completely different patterns of
supramolecular aggregation.
The molecules of (I) are linked into simple chains by means
of a single CÐHÁ Á ÁN hydrogen bond (Table 2). Aryl atom C13
in the molecule at (x, y, z) acts as a hydrogen-bond donor to
atom N1 in the molecule at (32 x, 21 + y, 23 z), so forming a
C(8) (Bernstein et al., 1995) chain running parallel to the [010]
3
direction and generated by the 21 screw axis along (34, y, )
4
(Fig. 3). Two chains of this type, related to each other by
inversion and hence antiparallel, pass through each unit cell,
but there are no direction-speci®c interactions between adja-
cent chains.
The molecules of (II) are linked by a combination of CÐ
HÁ Á ÁO and CÐHÁ Á Áꢀ(arene) hydrogen bonds (Table 4) into
Acta Cryst. (2006). C62, o583±o586
DOI: 10.1107/S0108270106032689
# 2006 International Union of Crystallography o583

organic compounds
Figure 1
The R enantiomer of (I), showing the atom-labelling scheme. Displace-
ment ellipsoids are drawn at the 30% probability level.
Figure 4
A stereoview of part of the crystal structure of (II), showing the
formation of a sheet parallel to (001), formed by the combination of [100]
and [010] chains. For the sake of clarity, H atoms not involved in the
motifs shown have been omitted.
sheets, whose formation is readily analysed in terms of two
simple one-dimensional substructures, each involving a single
hydrogen bond. In one substructure, aryl atom C25 in the
molecule at (x, y, z) acts as a hydrogen-bond donor to
carbonyl atom O1 in the molecule at ( 1 + x, y, z), so
generating by translation a C(8) chain running parallel to the
[100] direction (Fig. 4). In the second substructure, methylene
atom C27 in the molecule at (x, y, z) acts as a hydrogen-bond
donor, via H27A, to the C11±C16 aryl ring of the molecule at
(2 x, 12 + y, z + 32), so forming a chain running parallel to
the [010] direction and generated by the 21 screw axis along (1,
y, 34 ) (Fig. 4). The combination of these [100] and [010] chains
generates a sheet parallel to (001) (Fig. 4). Two such sheets,
generated by the 21 screw axes at z = 14 and z = 43, pass through
each unit cell, but there are no direction-speci®c interactions
between adjacent sheets. In neither of the structures of (I) and
(II) are there any aromatic ꢀ±ꢀ stacking interactions.
Figure 2
A molecule of (II), showing the atom-labelling scheme. Displacement
ellipsoids are drawn at the 30% probability level.
Experimental
For the synthesis of (I), methyl 2-cyanoacetate (0.0128 mol) was
added to a hot suspension (bath temperature 313 K) of potassium
carbonate (0.048 mol) in tetrahydrofuran (50 ml) and the mixture
was stirred for 30 min. Benzyl chloride (0.0245 mol) was then added
and the reaction mixture was heated under re¯ux for 36 h. The
mixture was cooled to ambient temperature, quenched by addition of
brine and extracted with ethyl acetate (2 Â 10 ml). The combined
organic extracts were dried over anhydrous sodium sulfate and the
solvent was removed under reduced pressure. The residue was
puri®ed by ¯ash chromatography (using 6% ethyl acetate in hexane
as eluant) to afford methyl 2-cyano-3-phenylpropionate, (III), as a
viscous yellow oil (yield 52%). A solution of ester (III) (2.64 mmol)
in tetrahydrofuran (3 ml) was added dropwise under argon to a
stirred suspension of potassium tert-butoxide (2.64 mmol) in anhy-
drous tetrahydrofuran (36 ml) at 393 K. After stirring for 10 min,
2-bromobenzyl bromide (2.64 mmol) in tetrahydrofuran (3 ml) was
Figure 3
Part of the crystal structure of (I), showing the formation of a C(8) chain
along [010] built from CÐHÁ Á ÁN hydrogen bonds. For the sake of clarity,
H atoms not involved in the motif shown have been omitted. Atoms
marked with an asterisk (*) or a hash (#) are at the symmetry positions
3
2
3
2
1
2
3
(
x, 12 + y,
z) and (32 x,
+ y,
2
z), respectively.
ꢀ
Â
o584 Calderon et al. C16H14BrN and C18H17NO2
Acta Cryst. (2006). C62, o583±o586

organic compounds
introduced slowly via syringe and the mixture was stirred for another
4 h at ambient temperature. The reaction was quenched by addition
of brine and the mixture was then extracted with ethyl acetate (2 Â
10 ml); the combined organic extracts were dried over anhydrous
sodium sulfate and the solvent was removed under reduced pressure.
The residue was puri®ed by ¯ash chromatography on silica (using 5%
ethyl acetate in hexane as eluant) to give methyl 2-benzyl-3-(2-
bromophenyl)-2-cyanopropionate, (IV), as a white powder (yield
68%, m.p. 365±366 K). A solution of ester (IV) (1.47 mmol) and
water (14 Â 10 3 ml) in dimethyl sulfoxide (2.0 ml) was added to a
heated solution (375 K) of lithium chloride (2.94 mmol) in dry
dimethyl sulfoxide (6.0 ml) under argon. This reaction mixture was
heated at 405 K for 45 min. After cooling to ambient temperature, the
reaction mixture was washed with brine (10 ml) and the organic layer
was extracted with n-pentane (3 Â 10 ml); the combined extracts
were dried with magnesium sulfate and the solvent was removed
under reduced pressure. The crude solid product was puri®ed by ¯ash
chromatography on silica with 10% (v/v) ethyl acetate/hexane as
eluant, affording a white powder, which was recrystallized from a
solution of ethyl acetate/hexane to provide colourless crystals of (I)
suitable for single-crystal X-ray diffraction (yield 48%, m.p. 351±
352 K); MS (m/z, %): 301/299 (12:11, M+), 171/169 (18/17,
[CH2C6H4Br]+), 91 (100, [C7H7]+). For the synthesis of (II), methyl
cyanoacetate (1.055 g, 0.01 mol) was added dropwise to a suspension
of potassium tert-butoxide (1.14 g, 0.01 mol) in anhydrous tetra-
hydrofuran (130 ml) at room temperature under an argon atmos-
phere. This mixture was stirred for 15 min, then benzyl chloride
(1.287 g, 0.01 mol) was added slowly, followed by stirring for 4 h at
ambient temperature. The reaction was then quenched by addition of
brine (10 ml) and the mixture was extracted with ethyl acetate (2 Â
10 ml); the combined organic extracts were dried over anhydrous
sodium sulfate and the solvent was removed under reduced pressure.
The residue was puri®ed by ¯ash chromatography to afford (II) as a
white powder; recrystallization from ethyl acetate gave colourless
crystals suitable for single-crystal X-ray diffraction (yield 92%, m.p.
354±355 K); MS (m/z, %): 279 (7, M+), 188 (20), 156 (6), 91 (100,
[C7H7]+).
Table 1
Selected geometric parameters (A, ) for (I).
ꢁ
Ê
N1ÐC1
1.146 (2)
C1ÐC2
1.472 (2)
C27ÐC2ÐC17ÐC11
C2ÐC17ÐC11ÐC12
170.00 (14)
81.6 (2)
C17ÐC2ÐC27ÐC21
C2ÐC27ÐC21ÐC22
74.01 (19)
99.62 (19)
Table 2
Hydrogen-bond geometry (A, ) for (I).
ꢁ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
C13ÐH13Á Á ÁN1i
0.95
2.58
3.294 (3)
132
Symmetry code: (i) x ‡ 32; y ‡ 21; z ‡ 23.
Compound (II)
Crystal data
C18H17NO2
Mr = 279.33
Z = 4
Dx = 1.181 Mg m
Mo Kꢂ radiation
ꢃ = 0.08 mm
T = 120 (2) K
Block, colourless
0.70 Â 0.45 Â 0.32 mm
3
Orthorhombic, P212121
Ê
1
a = 9.2000 (3) A
Ê
b = 9.3280 (2) A
Ê
c = 18.3031 (5) A
Ê
V = 1570.73 (7) A
3
Data collection
Bruker±Nonius KappaCCD
diffractometer
' and ! scans
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.938, Tmax = 0.976
13755 measured re¯ections
2053 independent re¯ections
1845 re¯ections with I > 2ꢄ(I)
Rint = 0.031
ꢅmax = 27.5ꢁ
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.031
wR(F2) = 0.076
S = 1.14
2053 re¯ections
w = 1/[ꢄ2(F2o) + (0.0366P)2
+ 0.1369P]
where P = (F2o + 2Fc2)/3
(Á/ꢄ)max < 0.001
Compound (I)
3
Ê
Áꢆmax = 0.17 e A
3
Ê
0.13 e A
192 parameters
H-atom parameters constrained
Áꢆmin
Extinction correction: SHELXL97
=
Crystal data
Extinction coef®cient: 0.036 (4)
C16H14BrN
Mr = 300.19
Monoclinic, P21=n
Ê
a = 9.7924 (2) A
Z = 4
Dx = 1.476 Mg m
Mo Kꢂ radiation
ꢃ = 3.02 mm
T = 120 (2) K
Plate, colourless
0.20 Â 0.15 Â 0.08 mm
3
1
Table 3
Selected geometric parameters (A, ) for (II).
ꢁ
Ê
Ê
b = 14.8921 (2) A
Ê
c = 10.0937 (2) A
ꢁ = 113.392 (2)ꢁ
V = 1350.98 (5) A
N1ÐC1
1.1428 (18)
C1ÐC2
1.4773 (19)
3
Ê
C27ÐC2ÐC17ÐC11
C2ÐC17ÐC11ÐC12
C1ÐC2ÐC3ÐO2
174.44 (12)
92.52 (16)
6.48 (17)
C17ÐC2ÐC27ÐC21
C2ÐC27ÐC21ÐC22
C2ÐC3ÐO2ÐC4
175.07 (12)
77.05 (17)
176.60 (14)
Data collection
Bruker±Nonius KappaCCD
diffractometer
' and ! scans
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.583, Tmax = 0.794
26393 measured re¯ections
3077 independent re¯ections
2554 re¯ections with I > 2ꢄ(I)
Rint = 0.040
ꢅmax = 27.5ꢁ
Table 4
Hydrogen-bond geometry (A, ) for (II).
ꢁ
Ê
Re®nement
Cg is the centroid of the C11±C16 ring.
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.027
wR(F2) = 0.062
S = 1.07
3077 re¯ections
w = 1/[ꢄ2(F2o) + (0.0287P)2
+ 0.3751P]
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
where P = (F2o + 2Fc2)/3
(Á/ꢄ)max = 0.001
C25ÐH25Á Á ÁO1i
0.95
0.99
2.53
2.77
3.467 (2)
3.6799 (15)
169
153
3
Ê
Áꢆmax = 0.23 e A
C27ÐH27AÁ Á ÁCgii
3
Ê
0.57 e A
163 parameters
H-atom parameters constrained
Áꢆmin
=
1
2
Symmetry codes: (i) x 1; y; z; (ii) x ‡ 2; y
;
z ‡ 32.
ꢀ
Â
Acta Cryst. (2006). C62, o583±o586
Calderon et al. C16H14BrN and C18H17NO2 o585

organic compounds
For compounds (I) and (II), the space groups P21/n and P212121,
respectively, were uniquely assigned from the systematic absences.
All H atoms were located in difference maps and then treated as
riding atoms, with CÐH distances of 0.95 (aromatic), 0.98 (CH3),
a scholarship grant supporting a short stay at the EPSRC
National Crystallography Service. GC and LMJG thank
COLCIENCIAS, UNIVALLE (Universidad del Valle,
Colombia), for ®nancial support.
Ê
0.99 (CH2) or 1.00 A (aliphatic CH), and with Uiso(H) = kUeq(C),
where k = 1.5 for the methyl group and 1.2 for all other H atoms. In
the absence of signi®cant resonant scattering, the absolute con®g-
uration of the molecules of (II) in the crystal selected for data
collection could not be established, but this con®guration has no
chemical signi®cance; accordingly, the Friedel-equivalent re¯ections
were merged prior to the ®nal re®nements.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GG3038). Services for accessing these data are
described at the back of the journal.
References
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to re®ne structure: OSCAIL (McArdle, 2003) and SHELXL97
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È
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ꢀ
Â
o586 Calderon et al. C16H14BrN and C18H17NO2
Acta Cryst. (2006). C62, o583±o586