(±)-7-Oxo-1,2,3,4,4a,5,6,7-octa-hydronaphthalene-1-acetic acid: Catemeric hydrogen bonding and diastereomeric disorder in a bicyclic unsaturated ε-keto acid

Article abstract of DOI:10.1107/S0108270104003075

The synthesis and crystal structure of (±)-7-Oxo-1,2,3,4,4a,5,6,7- octa-hydronapthalene-1-acetic acid were discussed. The 68.5:31.5 mixture of diasteroisomers obtained in the synthesis of the compound yielded sharply melting crystals containing the same r

Full text of DOI:10.1107/S0108270104003075

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
diastereomers arising from the chiral centers at C1 and C4a.
This disorder depends on positioning the carboxymethyl side
chain on an equatorial bond, (IA), versus an axial bond, (IB),
but also entails an accompanying ¯exing of the ring system.
Compound (I) was prepared from achiral materials and is
racemic. Hence, the total number of stereoisomers possible
(22 = 4) represents two diastereomeric racemates, and solution
of the data set reveals that both diastereomers are present at
the same site in the asymmetric unit. Independent of other
information, the disorder was optimally modeled in the least-
squares re®nement using a 65.6 (11):34.4 (11) ratio for the cis/
trans pair of molecules epimeric at C1, designated (IA) and
ISSN 0108-2701
(Æ)-7-Oxo-1,2,3,4,4a,5,6,7-octa-
hydronaphthalene-1-acetic acid:
catemeric hydrogen bonding and
diastereomeric disorder in a bicyclic
unsaturated "-keto acid
1
(IB), respectively. Subsequent H NMR analysis of the bulk
material from which the experimental crystal had been
obtained by recrystallization found a 68.5:31.5 ratio. The lack
of diastereomer selectivity in the crystallization process and
the sharp melting point found for these crystals (see Experi-
mental) imply that (IA) and (IB) ®t equally well into any
position in the crystal lattice with essentially no sacri®ce in
stability. Thus, it does not appear that either the packing
arrangement or the melting point would vary for any mixture
of (IA) and (IB), including the pure materials. We have not
attempted it experimentally, but the implication is that
separation of these epimers by recrystallization probably
cannot succeed, at least for the crystallization mode observed
here.
Mark Davison, Hugh W. Thompson and Roger A.
Lalancette*
Carl A. Olson Memorial Laboratories, Department of Chemistry, Rutgers University,
Newark, NJ 07102, USA
Correspondence e-mail: rogerlal@andromeda.rutgers.edu
Received 29 January 2004
Accepted 9 February 2004
Online 11 March 2004
The 68.5:31.5 mixture of diastereoisomers obtained in the
synthesis of the title compound, C12H16O3, yielded sharply
melting crystals containing the same ratio of epimers, in a
disordered crystallographic arrangement. The disorder resides
almost entirely in the carboxymethyl side chain, but places the
two sets of carboxyl O atoms at nearly identical paired spatial
positions. Neither component displays signi®cant carboxyl
disorder, and the molecules aggregate as hydrogen-bonded
Ê
carboxyl-to-ketone catemers [OÁ Á ÁO = 2.673 (4) A and OÐ
HÁ Á ÁO = 158ꢀ] having glide-related components, with centro-
symmetrically related pairs of chains following axes perpen-
dicular to b. Close intermolecular CÐHÁ Á ÁO contacts exist for
both the ketone and the carboxyl group. The energetics of the
epimers and of their crystallization mode are discussed.
Comment
We believe that the observed 68.5:31.5 bulk ratio represents
a near-equilibrium mixture of epimers (see Experimental). If
attached to a simple cyclohexane ring, a carboxymethyl
substituent such as ours should occupy an equatorial bond
Our study of the crystal structures of keto carboxylic acids
concerns the molecular factors that determine their ®ve
known hydrogen-bonding modes. The dominant carboxyl-
pairing mode is known to be inhibited whenever centrosym-
metry is thwarted (Lalancette & Thompson, 2003) or mole-
cular ¯exibility is severely curtailed (Barcon et al., 2002).
Consequently, we have often focused our attention on single
enantiomers and on cyclic systems. The title compound, (I), an
example of the latter case, allows full rotation about only two
of its 12 CÐC single bonds, and the observed hydrogen
bonding involves formation of carboxyl-to-ketone chains
(catemers). Also revealed is a disorder due to the presence of
two isomers occupying the same site in the crystal.
more than 90% of the time at equilibrium, re¯ecting a free-
1
energy advantage of ca 1.7 kcal mol
1
(Hirsch, 1967;
1 kcal mol = 4.184 kJ mol 1). At the temperature of our
preparative reaction (353 K), our 68.5:31.5 equilibrium
corresponds to
a free-energy difference of only ca
0.55 kcal mol 1. This diminished equatorial preference rela-
tive to cyclohexane is probably associated with the close
juxtaposition in (IA) between atom C9 and the vinyl atom H8
®ve atoms away. The arrangement around the double bond in
(IA) places the C atom equatorially attached to C1 in the
Ê
Fig. 1 illustrates an asymmetric unit of (I), with the atom-
numbering scheme. The disorder indicated by the ghost bonds
and atoms used for C10 and C90 is due to the presence of two
plane of the alkene and at a distance of 2.65 A from atom H8.
In terms of steric hindrance, this spatial relationship is at least
the functional equivalent of a 1,3-diaxial CÐH interaction in a
o242 # 2004 International Union of Crystallography
DOI: 10.1107/S0108270104003075
Acta Cryst. (2004). C60, o242±o244

organic compounds
saturated cyclohexane system, where the distance would
Ê
typically be ca 2.8 A. The corresponding distances in the
minor component, (IB), between atom C90 and its own axial H
Ê
atoms are only 3.35 and 3.40 A for atoms C3 and C4a,
respectively. This occurs because (at least in the crystal) a twist
about the C7ÐC8 bond rotates the alkene and thus C10 so that
its substituents are no longer strictly axial and equatorial with
respect to its ring, as may be seen in Fig. 1. The extent of this
rotation is also visible and measurable in Fig. 1 as the C1Ð
C8aÐC10 angle [27.6 (3)ꢀ].
Dimeric carboxyls often appear with CÐO bonds and CÐ
CÐO angles fully or partially averaged by disorder, since that
mode permits either tautomeric or rotational transposition of
the two O atoms without disruption of the overall hydrogen-
bonding scheme. Carboxyls involved in non-dimeric arrange-
ments, however, are invariably highly ordered. In (I), these
Ê
CÐO lengths are 1.205 (5) and 1.250 (6) A, representing
signi®cantly less differentiation of the O atoms than is seen in
other catemeric cases. Our own survey of 56 keto acid struc-
tures that are not dimers gives average values of 1.20 (1) and
Figure 2
A packing diagram for (I), including extracellular molecules to illustrate
the counterdirectionally paired carboxyl-to-ketone glide catemers. All C-
bound H atoms have been removed for clarity. Displacement ellipsoids
are drawn at the 20% probability level.
Ê
1.32 (2) A for such lengths, in accord with typical values of
Ê
1.21 and 1.31 A cited for highly ordered dimeric carboxyls
(Borthwick, 1980). Accompanying this apparent partial aver-
aging in length is a set of distorted CÐCÐO bond angles for
the carboxyl (Table 1), which deviate considerably from the
ideal. (The surveys of highly ordered dimeric carboxyls cited
above give average values in the ranges 123±125 and 112±
113ꢀ.) However, all the carboxyl atoms in (I) have very high
anisotropies, more consistent with diastereomeric disorder
rather than with the routine `carboxyl' disorder arising from
tautomeric hydrogen exchange or other oxygen-transposing
mechanisms. In addition, we were unable to ®nd signi®cant
electron density for any partial H atom associated with O2. We
therefore believe that the various distortions in the carboxyl
are actually an artifact of the diastereomeric disorder evident
in C1 and C9, and of our inability to separate the merged
carboxyls for modeling purposes.
Fig. 2 illustrates the packing of the disordered molecules of
(I) and their hydrogen-bonding arrangement, which involves
catemers having glide-related components. The centrosym-
metry of the cell generates counterdirectional pairs of chains,
the glide axes of which lie perpendicular to b. Overall, the
prevalence of subtypes among catemers has been found to be
screw > translation > glide.
We characterize the geometry of hydrogen bonding to
carbonyls using a combination of the HÁ Á ÁO C angle and the
HÁ Á ÁO CÐC torsion angle. These describe the approach of
the H atom to the O atom in terms of its deviation from,
respectively, C O axiality (ideal = 120ꢀ) and planarity with
the carbonyl group (ideal = 0ꢀ). In (I), these angles are,
respectively, 132 and 18.9ꢀ.
Ê
Both the ketone group (2.64 A to H9A) and atom O3
Ê
(2.64 A to H4A) were found to have close CÐHÁ Á ÁO contacts
to separate neighboring molecules, related by a screw axis and
by translation, respectively. These distances lie within the
Ê
2.7 A range we usually employ for non-bonded HÁ Á ÁO packing
interactions (Steiner, 1997). Using compiled data for a large
number of CÐHÁ Á ÁO contacts, Steiner & Desiraju (1998)
found signi®cant statistical directionality even as far out as
Ê
3.0 A, and concluded that these are legitimately viewed as
`weak hydrogen bonds', with a greater contribution to packing
forces than simple van der Waals attractions.
The solid-state (KBr) IR spectrum of (I) displays separated
C
O absorptions at 1721 and 1638 cm 1, typical for,
respectively, a carboxyl lacking, and a conjugated ketone
having, hydrogen bonding. The peak at lower frequency is
broadened, presumably by the slightly differing degrees of
conjugation in (IA) and (IB) due to the C7ÐC8 twist in the
latter. In CHCl3 solution, where carboxyl dimers predominate,
these absorptions appear, normally and with similar breadth,
Figure 1
The asymmetric unit of (I) with the atom-numbering scheme. The
disorder in atoms C1 and C9 is represented by ghost bonds, with primed
numbering for the minor isomer, (IB). Displacement ellipsoids are drawn
at the 20% probability level and H atoms are shown as small spheres of
arbitrary radii.
ꢁ
Acta Cryst. (2004). C60, o242±o244
Mark Davison et al. C12H16O3 o243

organic compounds
at 1712 and 1667 cm 1, along with an alkene peak at
Table 1
Selected geometric parameters (A, ).
ꢀ
Ê
1
1622 cm
1745 cm
and a typical carboxyl-dilution shoulder near
1
.
O2ÐC10
1.205 (5)
132.8 (6)
O3ÐC10
1.250 (6)
104.6 (5)
O2ÐC10ÐC9
O3ÐC10ÐC9
Experimental
Compound (I) was prepared via the pyrrolidine enamine of cyclo-
hexanone. Alkylation with ethyl bromoacetate (Segre et al., 1957;
Stork et al., 1963) was followed by neutralization with sodium
ethoxide. Concentration in vacuo and distillation then yielded the
alkylated enamine, the Robinson annulation of which with methyl
vinyl ketone provided the bicyclic keto ester, which was puri®ed by
Table 2
Hydrogen-bonding geometry (A, ).
ꢀ
Ê
DÐHÁ Á ÁA
O3ÐH3Á Á ÁO1i
Symmetry code: (i) ‡ x; 12 y; 21 ‡ z.
DÐH
HÁ Á ÁA
1.89
DÁ Á ÁA
DÐHÁ Á ÁA
0.82
2.573 (4)
158
distillation. Subsequent saponi®cation yielded (I) as
a solid
1
2
containing a 68.5:31.5 mixture of epimers (IA) and (IB), as assessed
by 1H NMR [vinyl peaks at ꢀ 5.77 (s) and 5.93 (d, J = 2 Hz),
respectively]. Equilibration experiments with the ethyl ester of the
C13 side-chain (C15H22O3) homolog of (I) suggest that this ratio
probably represents a near-equilibrium mixture of (IA) and (IB),
likely arising during the annulation sequence itself, rather than
merely during saponi®cation. Recrystallization of (I) from ethyl
acetate gave crystals suitable for X-ray analaysis, which melted
sharply at 368±371 K.
All H atoms for (I) were found in electron-density difference maps
Ê
but were placed in calculated positions (CÐH distances of 0.97 A for
Ê
Ê
methylene, 0.98 A for methine and 0.93 A for vinyl H, and an OÐH
Ê
distance of 0.82 A for the hydroxyl H atom) and were allowed to
re®ne as riding models on their respective C and O atoms, with
Uiso(H) = 1.2Ueq(C) and 1.5Ueq(O).
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; software used to prepare
material for publication: SHELXL97.
Crystal data
3
C12H16O3
Mr = 208.25
Dx = 1.259 Mg m
Mo Kꢂ radiation
Cell parameters from 34
re¯ections
Monoclinic, P21=n
Ê
a = 10.354 (2) A
ꢃ = 2.2±9.4ꢀ
ꢄ = 0.09 mm
T = 296 (2) K
Ê
b = 8.269 (2) A
1
Ê
c = 13.512 (3) A
ꢁ = 108.27 (2)ꢀ
V = 1098.5 (4) A
Z = 4
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FR1467). Services for accessing these data are
described at the back of the journal.
3
Ê
Hexagonal rod, colorless
0.25 Â 0.22 Â 0.14 mm
Data collection
Siemens P4 diffractometer
2ꢃ/ꢃ scans
h = 12 ! 1
k = 9 ! 1
References
2624 measured re¯ections
1942 independent re¯ections
1083 re¯ections with I > 2ꢅ(I)
Rint = 0.038
l = 15 ! 16
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Sheldrick, G. M. (1997). SHELXTL. Version 5.10. Bruker AXS Inc., Madison,
Wisconsin, USA.
3 standard re¯ections
every 97 re¯ections
intensity variation: <1.7%
ꢃmax = 25.0ꢀ
Re®nement
Re®nement on F2
R[F2 > 2ꢅ(F2)] = 0.062
wR(F2) = 0.171
(Á/ꢅ)max < 0.001
3
Ê
Áꢆmax = 0.18 e A
3
Ê
0.22 e A
Áꢆmin
=
S = 1.02
1942 re¯ections
156 parameters
Extinction correction: SHELXL97
in SHELXTL (Sheldrick, 1997)
Extinction coef®cient: 0.017 (4)
Siemens (1996). XSCANS. Version 2.2. Siemens Analytical X-ray Instruments
Inc., Madison, Wisconsin, USA.
Steiner, T. (1997). J. Chem. Soc. Chem. Commun. pp. 727±734.
Steiner, T. & Desiraju, G. R. (1998). J. Chem. Soc. Chem. Commun. pp. 891±
892.
H-atom parameters constrained
w = 1/[ꢅ2(Fo2) + (0.0617P)2
+ 0.3911P]
Stork, G., Brizzolara, A., Landesman, H., Szmuszkovicz, J. & Terrell, R.
(1963). J. Am. Chem. Soc. 85, 207±222.
where P = (Fo2 + 2Fc2)/3
ꢁ
o244 Mark Davison et al.
C12H16O3
Acta Cryst. (2004). C60, o242±o244