(±)-2-oxocyclohexanepropionic acid: Dual conformational selection and hydrogen bonding in a δ-keto acid, and a two-phase technique for crystallizing acids by contact with aqueous solutions of their salts

Article abstract of DOI:10.1107/S0108270103020638

The asymmetric unit of the title compound, C₉H₁₄O₃, consists of two molecules having conformations that differ by 121.7 (4)° in their rotation about the equatorial substituent bond, so that the side chain extends away from

Full text of DOI:10.1107/S0108270103020638

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
the title compound, (I), and we discuss the crystallization
technique employed to produce the crystal used (see Experi-
mental).
ISSN 0108-2701
Fig. 1 presents a view of the asymmetric unit of (I) with its
numbering scheme. While the category of ꢀ-keto acids to
which (I) belongs encompasses a rich variety of hydrogen-
bonding types, the mode here is carboxyl dimerization. The
two molecules in this unit, viz. (IA) and (IB), are of identical
chirality, but differ in the conformations of their side chains.
Hence, despite the centrosymmetry in the space group (P1),
the dimer shown has no symmetry. This is only the third
instance we have encountered of the formation of an asym-
metric dimer within a centrosymmetric space group (Lalan-
cette et al., 1991, 1996), and surveys have shown that the
combination is a very uncommon one (Gavezzotti & Filippini,
(
Æ)-2-Oxocyclohexanepropionic acid:
dual conformational selection and
hydrogen bonding in a d-keto acid,
and a two-phase technique for
crystallizing acids by contact with
aqueous solutions of their salts
1
994; Allen et al., 1999), particularly if the survey set is edited
Roger A. Lalancette* and Hugh W. Thompson
to contain only acids capable of packing centrosymmetrically
(Sùrensen & Larsen, 2003).
Carl A. Olson Memorial Laboratories, Department of Chemistry, Rutgers University,
Newark, NJ 07102, USA
In both conformers of (I), the substituent chain extends
equatorially from the ring and adopts a standard staggered
arrangement about both C1ÐC7 and C7ÐC8. However, the
staggering constraint still permits three rotational options
about each of those bonds, and only conformer (IA) adopts a
conformation with a fully anti arrangement of substituents,
which extends into the ring to the ketone C2 atom. By
Correspondence e-mail: rogerlal@andromeda.rutgers.edu
Received 29 July 2003
Accepted 18 September 2003
Online 22 October 2003
The asymmetric unit of the title compound, C H O , consists
9
14
3
0
contrast, conformer (IB) has an anti arrangement about C7 Ð
of two molecules having conformations that differ by
ꢀ
0
0
0
C8 but a gauche conformation about C1 ÐC7 . The latter is
presumably permitted by the absence of a hindering axial H
atom at the ketone C atom. The chains in (IA) and (IB) differ
in their rotation about the C1ÐC7 bond by almost exactly
1
21.7 (4) in their rotation about the equatorial substituent
bond, so that the side chain extends away from the ring in
different directions in the two species. The hydrogen-bonding
mode is acid-to-acid dimerization. However, despite the
centrosymmetric space group (P1), the dimers are asymmetric,
formed by pairing molecules of identical chirality but differing
ꢀ
ꢀ
1
20 ; in (IA), the C6ÐC1ÐC7ÐC8 torsion angle is 60.9 (3) ,
ꢀ
while the corresponding angle in (IB) is � 60.8 (3) , yielding a
ꢀ
Ê
difference of 121.7 (4) for this pair of conformers. The
remaining torsion angles within the side chain vary only
conformational type [OÁ Á ÁO = 2.681 (2) and 2.654 (2) A, and
ꢀ
OÐHÁ Á ÁO = 175 (3) and 176 (3) ]. Two intermolecular CÐ
slightly between (IA) and (IB), with nearly identical angles for
ꢀ
HÁ Á ÁO C close contacts exist, involving the ketone group of
one of the molecules. A two-phase technique is described for
slow reforming of crystals of a water-insoluble acid by contact
with an aqueous solution of its water-soluble salt.
C1ÐC7ÐC8ÐC9 [173.0 (2) and � 171.6 (2) , respectively]
ꢀ
and O2ÐC9ÐC8ÐC7 [� 6.5 (4) and � 8.9 (4) , respectively].
The result, as to the conformation about the equatorial C1Ð
C7 bond, resembles rotation of a rigid rotor. One consequence
of this rotation is that the internal carboxyl versus ketone
Comment
ꢀ
ꢀ
dihedral angle is 0.88 (15) in (IA) but 63.44 (7) in (IB).
Although averaging of CÐO bond lengths and CÐCÐO
angles by disorder is common in dimerized carboxyls
(Leiserowitz, 1976), neither conformer of (I) displays signi®-
When a ketone and a carboxylic acid co-exist within a single
molecule, the excess of hydrogen-bond receptors over donors
provides hydrogen-bonding opportunities beyond those
available to simple acids. Our long-term study of the crystal-
lography of keto acids has offered numerous examples
encompassing all ®ve of the known hydrogen-bonding modes,
Figure 1
Aview of the asymmetric unit of (I) with the atom-numbering scheme for
conformer (IA). The two halves of the non-centrosymmetric dimer, of
identical chirality, differ in conformation by rotation about C1ÐC7.
Displacement ellipsoids are drawn at the 20% probability level and H
atoms are shown as small spheres of arabitrary radii.
along with discussions of the factors that contribute to the
choice of mode (Lalancette et al., 1998, 1999; Brunskill et al.,
1999). As part of a continuing study of simple cyclohexane and
cyclopentane keto acids, we report here the crystal structure of
o638 # 2003 International Union of Crystallography
DOI: 10.1107/S0108270103020638
Acta Cryst. (2003). C59, o638±o640

organic compounds
cant carboxyl disorder, which may result in part from the
complete absence of symmetry in the dimer. In (IA), the CÐO
Experimental
The pyrrolidine enamine of cyclohexanone was alkylated with ethyl
acrylate (Stork et al., 1963), yielding the ethyl ester of (I), which was
puri®ed by distillation. Saponi®cation followed by recrystallization
gave material of melting point 337 K. Exhaustive crystallization trials
with numerous solvents and solvent combinations invariably yielded
ultra®ne needles of (I) unsuitable for X-ray analysis. Usable crystals
of (I) (m.p. 340 K) were produced from an aqueous medium by the
following technique. Compound (I) was added, with stirring and
warming, to an 8 ml vial containing aqueous NaOH (about 4 ml) until
the pH of the solution was neutral; the speci®c gravity of the ®nal
solution was 1.03. Additional (I) was added to provide a clot of
undissolved keto acid lying in the bottom of the vial, and the vial was
tightly capped and placed in a sunlit position providing periodic
temperature variation. Over a period of weeks, the solid in the
bottom gradually clari®ed and produced chunky faceted clear
projections and extensions, principally on its bottom surface. After
several months, the mass was broken up and the liquor removed by
pipette and retained in a second vial. The crystals were rinsed with
water, gently broken into smaller units and dried. After removal of
suitable candidates, unusable crystals were reunited with the retained
liquor for further reforming.
Ê
bond lengths are 1.217 (3) and 1.304 (3) A, with CÐCÐO
ꢀ
angles of 123.6 (2) and 114.1 (2) ; the corresponding bond
Ê
lengths for (IB) are 1.218 (3) and 1.308 (3) A, with angles of
ꢀ
1
ordered dimeric carboxyls are 1.21 and 1.31 A, and 123 and
24.4 (2) and 113.3 (2) . Typical values cited for highly
Ê
ꢀ
1
12 (Borthwick, 1980). Because of the absence of symmetry,
Ê
the OÁ Á ÁO distances in the dimer are different [2.681 (2) A for
0
Ê
0
O3Á Á ÁO2 versus 2.654 (2) A for O3 Á Á ÁO2], although the
OÐHÁ Á ÁO angles are statistically indistinguishable.
Crystal data
C
9
H
14
O
3
Z = 4
= 1.244 Mg m
Mo Kꢁ radiation
�
3
M
r
= 170.20
Triclinic, P1
D
x
Ê
Ê
Ê
ꢀ
a = 5.4302 (9) A
b = 13.370 (2) A
c = 14.075 (2) A
ꢁ
ꢂ = 86.956 (12)
ꢃ = 85.297 (14)
Ê
V = 908.9 (3) A
Cell parameters from 34
re¯ections
ꢀ
ꢄ = 3.2±10.5
� 1
= 63.198 (11)
ꢅ = 0.09 mm
T = 296 (2) K
ꢀ
ꢀ
Parallelepiped, colorless
0.28 Â 0.26 Â 0.08 mm
3
Figure 2
A partial packing diagram for (I), with extra molecules included.
Data collection
Siemens P4 diffractometer
Rint = 0.025
ꢄmax = 25.0
ꢀ
2
ꢄ/ꢄ scans
Absorption correction: numerical
SHELXTL; Sheldrick, 1997)
min = 0.96, Tmax = 0.99
166 measured re¯ections
3104 independent re¯ections
995 re¯ections with I > 2ꢆ(I)
h = � 1 ! 6
(
T
k = � 14 ! 14
Fig. 2 illustrates the packing of the cell of (I). All the dimers
lie bundled with their long axes parallel and lying generally in
the c direction. Because the dimers lack any symmetry, their
centres do not lie on a special position, although they lie quite
l = � 16 ! 16
4
3 standard re¯ections
every 97 re¯ections
intensity variation: <1.5%
1
1
4
3 3
4 4
close to ( , , ), at (0.23, 0.74, 0.75) (and the corresponding
centrosymmetric site). In the packing, two intermolecular CÐ
Re®nement
2
2
2
2
Re®nement on F
2
o
w = 1/[ꢆ (F ) + (0.0651P)
2
HÁ Á ÁO C close contacts were found, both involving the
R[F > 2ꢆ(F )] = 0.052
wR(F ) = 0.145
S = 1.02
3104 re¯ections
224 parameters
H atoms treated by a mixture of
independent and constrained
re®nement
+ 0.1786P]
where P = (F
(Á/ꢆ)max < 0.001
2
2
2
c
Ê
ketone group of molecule (IA), with a distance of 2.60 A to
o
+ 2F
)/3
Ê
atom H8B and 2.51 A to atom H3 A, in separate translation-
0
� 3
Ê
Áꢇmax = 0.18 e A
Ê
� 3
ally related asymmetric units. These contacts lie within the
Ê
Áꢇmin = � 0.14 e A
Extinction correction: SHELXTL
(Sheldrick, 1997)
Extinction coef®cient: 0.011 (3)
2
.7 A range we standardly employ for non-bonded CÐHÁ Á ÁO
packing interactions (Steiner, 1997). Using compiled data for a
large number of such contacts, Steiner & Desiraju (1998) have
found statistically signi®cant directionality even as far out as
Ê
All H atoms were found in electron-density difference maps.
C-bound H atoms were placed in calculated positions (CÐH = 0.97 AÊ
3
.0 A, and conclude that these are legitimately viewed as
weak hydrogen bonds', with a greater contribution to packing
`
forces than simple van der Waals attractions.
Table 1
Selected geometric parameters (A, ).
Ê
ꢀ
The solid-state (KBr) IR spectrum of (I) has a single
�
1
stretching absorption at 1698 cm for both C O functions in
both species, typical for acids that have, and unstrained
ketones that lack, hydrogen bonding. In CHCl solution, this
0
0
0
0
O2ÐC9
O3ÐC9
1.217 (3)
1.304 (3)
O2 ÐC9
O3 ÐC9
1.218 (3)
1.308 (3)
3
�
1
0
0
0
0
0
0
peak appears at 1709 cm , broadened by the usual carboxyl-
�
O2ÐC9ÐC8
O3ÐC9ÐC8
123.6 (2)
114.1 (2)
O2 ÐC9 ÐC8
O3 ÐC9 ÐC8
124.4 (2)
113.3 (2)
1
dilution shoulder at ca 1750 cm .
ꢁ
Acta Cryst. (2003). C59, o638±o640
Lalancette and Thompson
9
C H
O
14 3
o639

organic compounds
Table 2
Hydrogen-bonding geometry (A, ).
References
Ê
ꢀ
Allen, F. H., Motherwell, W. D. S., Raithby, P. R., Shields, G. P. & Taylor, R.
(
1999). New J. Chem. 23, 25±34.
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
Borthwick, P. W. (1980). Acta Cryst. B36, 628±632.
Brunskill, A. P. J., Thompson, H. W. & Lalancette, R. A. (1999). Acta Cryst.
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0
O3ÐH3Á Á ÁO2
0.94 (3)
0.87 (3)
1.75 (3)
1.79 (3)
2.681 (2)
2.654 (2)
175 (3)
176 (3)
0
0
O3 ÐH3 Á Á ÁO2
Ê
for methylene H and 0.98 A for methine H atoms) and allowed to
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244±246.
1
20% of those of their respective C atoms. The hydroxyl H atoms
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Inc., Madison, Wisconsin, USA.
were allowed to vary positionally and their displacement parameters
were ®xed at 150% of those of their respective O atoms.
Data collection: XSCANS (Siemens,1996); cell re®nement:
XSCANS; data reduction: XSCANS; program(s) used to solve
structure: SHELXS97 in SHELXTL (Sheldrick, 1997); program(s)
used to re®ne structure: SHELXL97 in SHELXTL; molecular
graphics: SHELXP97 in SHELXTL.
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described at the back of the journal.
8
92.
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1963). J. Am. Chem. Soc. 85, 207±222.
(
ꢁ
o640 Lalancette and Thompson
9
C H
O
14 3
Acta Cryst. (2003). C59, o638±o640