Cubanecarboxylic acids. Crystal engineering considerations and the role of C-H...O hydrogen bonds in determining O-H...Onetworks

Article abstract of DOI:10.1021/ja981967u

A family of 4-substituted-1-cubanecarboxylic acids have been synthesized and their X-ray crystal structures analyzed. The rare syn-anti O-H...O catemer 6 is a recurring pattern in this series of compounds. Catemer 6 is observed in the crystal structures o

Full text of DOI:10.1021/ja981967u

1936
J. Am. Chem. Soc. 1999, 121, 1936-1944
Cubanecarboxylic Acids. Crystal Engineering Considerations and the
Role of C-H‚‚‚O Hydrogen Bonds in Determining O-H‚‚‚O
Networks
†
‡
,†
,†
Srinivasan S. Kuduva, Donald C. Craig, Ashwini Nangia,* and Gautam R. Desiraju*
Contribution from the School of Chemistry, UniVersity of Hyderabad, Hyderabad 500 046, India, and
School of Chemistry, UniVersity of New South Wales, Sydney 2052, Australia
ReceiVed June 5, 1998. ReVised Manuscript ReceiVed December 3, 1998
Abstract: A family of 4-substituted-1-cubanecarboxylic acids have been synthesized and their X-ray crystal
structures analyzed. The rare syn-anti O-H‚‚‚O catemer 6 is a recurring pattern in this series of compounds.
Catemer 6 is observed in the crystal structures of 4-chloro-1-cubanecarboxylic acid (10), 4-bromo-1-
cubanecarboxylic acid (11), 4-iodo-1-cubanecarboxylic acid (12), and 4-(methoxycarbonyl)-1-cubanecarboxylic
acid (13). The ready occurrence of catemer 6 in this family is ascribed to its stabilization by auxiliary
C-H‚‚‚O hydrogen bonds formed by the relatively acidic cubyl C-H groups. The frequency of occurrence of
6
also facilitates its definition as a useful supramolecular synthon. As is true in many catemers, the formation
of 6 is sensitive to steric factors. Therefore, the robustness of this synthon may be assessed by analyzing the
crystal structures of molecules wherein the 4-substituent is too small (R ) H, 14), too large (R ) Ph, 15), or
has a specific hydrogen bonding preference of its own (R ) CONH2, 16). In these structures, either dimer 3
(in 14 and 15) or heterodimer 22 (in 16) is observed. Powder diffraction shows that the previously noted
structure of 1,4-cubanedicarboxylic acid (7) that contains catemer 6 is characteristic of the bulk material. In
summary, the syn-anti catemer is the dominant supramolecular synthon in this family of cubanecarboxylic
acids.
Introduction
molecular interactions,7 a consideration of supramolecular
synthons constructed with strong and weak hydrogen bonds
generally provides a more complete understanding of crystal
packing.
Hydrogen bond patterns in carboxylic acid crystal structures
have been described in detail by Leiserowitz and co-workers.8
The carboxylic acid group occurs in two distinct conformations,
The physical and chemical properties of an organic crystal
are determined by the nature of the constituent molecules as
well as by the mutual orientation and interactions between these
1
molecules. Crystal engineering is the design and construction
2
of crystal structures from molecular components. A crystal
structure may be analyzed in terms of supramolecular synthons,
3
(4) Selected examples on the use of strong and weak hydrogen bonding
defined as structural units within supermolecules which can be
formed and/or assembled by known or conceivable inter-
molecular interactions. Crystal engineering then is carried out
by the identification of a molecular skeleton with specific
functional groups that will predictably and persistently lead to
robust synthons and therefore to the target crystal structure.
Hydrogen bonds and other intermolecular interactions have been
studied in depth because they provide viable approaches toward
the design of molecular solids with specific supramolecular
architectures and functions.4,5 Hydrogen bonds are formed with
strong donor-acceptor functionalities (OH, NH2, CO2H, CONH2)
in crystal engineering strategies: (a) Schwiebert, K. E.; Chin, D. N.;
MacDonald J. C.; Whitesides, G. M. J. Am. Chem. Soc. 1996, 118, 4018.
(
b) Lewis, F. D.; Yang, J.; Charlotte, L. S. J. Am. Chem. Soc. 1996, 118,
12029. (c) Coe, S.; Kane, J. J.; Nguyen, T. L.; Toledo, L. M.; Wininger,
E.; Fowler, F. W.; Lauher, J. W. J. Am. Chem. Soc. 1997, 119, 86. (d)
Bhyrappa, P.; Wilson, S. R.; Suslick, K. S. J. Am. Chem. Soc. 1997, 119,
8492. (e) MacGillivray, L. R.; Atwood, J. L. Nature 1997, 389, 469. (f)
Endo, K.; Ezuhara, T.; Koyanagi, M.; Masuda, H.; Aoyama, Y. J. Am. Chem.
Soc. 1997, 119, 499. (g) Karle, I. L.; Ranganathan, D.; Haridas, V. J. Am.
Chem. Soc. 1997, 119, 2777. (h) Thalladi, V. R.; Brasselet, S.; Weiss, H.-
C.; Bl a¨ ser, D.; Katz, A. K.; Carrell, H. L.; Boese, R.; Zyss, J.; Nangia, A.;
Desiraju, G. R. J. Am. Chem. Soc. 1998, 120, 2563.
(5) Selected recent reviews on hydrogen bonding in crystal engineer-
ing: (a) Fyfe, M. C. T.; Stoddart, J. F. Acc. Chem. Res. 1997, 30, 393. (b)
Desiraju, G. R. Chem. Commun. 1997, 1475. (c) Aaker o¨ y, C. B. Acta
Crystallogr. 1997, B53, 569. (d) Hosseini, M. W.; Cian, A. D. Chem.
Commun. 1998, 727. (e) Nangia, A.; Desiraju, G. R. Acta Crystallogr. 1998,
A54, 934.
(6) Selected reviews on hydrogen bonding: (a) Jeffrey, G. A.; Saenger,
W. Hydrogen Bonding in Biological Structures; Springer-Verlag: Berlin,
1991. (b) Aaker o¨ y, C. B.; Seddon, K. R. Chem. Soc. ReV. 1993, 22, 397.
(c) MacDonald, J. C.; Whitesides, G. M. Chem. ReV. 1994, 94, 2383. (d)
Desiraju, G. R. Acc. Chem. Res. 1996, 29, 441. (e) Steiner, T. Chem.
Commun. 1997, 727. (f) Jeffrey, G. A. An Introduction to Hydrogen
Bonding; Oxford University Press: New York, 1997.
3
and with weak donors (CtC-H, C6H5, CdC-H, C(sp )-H)
and acceptors (CN, NO2, halogen, π). Because crystal structures
are the results of interplay between strong and weak inter-
6
†
University of Hyderabad.
University of New South Wales.
‡
(1) (a) Desiraju, G. R. Science 1997, 278, 404. (b) Desiraju, G. R. Curr.
Opin. Solid State Mater. Sci. 1997, 2, 451. (c) Bryce, M. R., Ed. J. Mater.
Chem. 1997, 7, 1069 (special issue on molecular assemblies and nanochem-
istry). (d) Hosseini, M. W., Ed. New J. Chem. 1998, 22, 87 (special issue
on molecular networks).
(
2) (a) Desiraju, G. R. Crystal Engineering: The Design of Organic
(7) (a) Dunitz, J. D. The Crystal as a Supramolecular Entity, PerspectiVes
in Supramolecular Chemistry; Desiraju, G. R., Ed.; Wiley: Chichester, U.K.,
1996; Vol. 2, pp 1-30. (b) Desiraju, G. R. Sharma, C. V. K. The Crystal
as a Supramolecular Entity, PerspectiVes in Supramolecular Chemistry;
Desiraju, G. R., Ed.; Wiley: Chichester, U.K., 1996; Vol. 2, pp 31-61.
Solids; Elsevier: Amsterdam, 1989. (b) Anthony, A.; Desiraju, G. R.; Jetti,
R. K. R.; Kuduva, S. S.; Madhavi, N. N. L.; Nangia, A.; Thaimattam, R.;
Thalladi, V. R. Cryst. Eng. 1998, 1, 1.
(3) Desiraju, G. R. Angew. Chem., Int. Ed. Engl. 1995, 34, 2311.
1
0.1021/ja981967u CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/19/1999

Cubanecarboxylic Acids
J. Am. Chem. Soc., Vol. 121, No. 9, 1999 1937
synplanar 1 and antiplanar 2. The syn conformation is more
stable (by ca. 2 kcal/mol) and is thus preferred. The most
frequent and indeed dominant interlink adopted by carboxylic
acids is the syn-syn centrosymmetric dimer 3. In addition,
tion. Two of the syn carboxylic H atoms are hydrogen bonded
to different water molecules. The prominent feature in this
abstruse crystal structure is again hydrogen bonding between
syn and anti carboxylic acid groups, though it is interrupted by
water molecules. The carboxylic acid is a strong hydrogen
bonding functional group that is associated with robust and
reliable patterns for solid-state supramolecular aggregation,14
and yet instead of the usually observed syn-syn dimer 3, the
rare catemer 6 or its hydrated variant are found in the only two
reported crystal structures of cubanecarboxylic acids. It is this
enigmatic and unexplained behavior of 7 and 8 that, in part,
led to the present study.
The cubane skeleton is a rigid framework on which functional
groups can be attached in specific orientations. Cubanes have
potential applications in pharmaceuticals, polymers, explosives,
15
and materials chemistry. Cubanecarboxylic acids are excellent
core units for derivatization with amino acids in combinatorial
1
6
however, catemers of the types 4 (syn-syn) and 5 (anti-anti)
are formed. A third catemer, pattern 6 with alternating syn and
chemistry. Thus, the molecular chemistry of the cubane
skeleton is well-developed and advances in the synthesis of
highly functionalized cubanes continue to be reported.17 How-
ever, the supramolecular behavior of cubanes in the solid state
has not been systematically examined and this is surprising,
given the relatively high acidity of the cubyl H atom.18 The
9
anti carboxylic acid groups has also been observed. A search
of the Cambridge Structural Database10 (CSD, version 5.15) was
1
1
carried out on these four distinct hydrogen bond patterns. Of
the three catemeric arrangements, the syn-syn is the most
common. The anti-anti catemer 5 and the syn-anti variant 6
are, however, extremely rare with only two and three occur-
rences, respectively, in the CSD.
acidity of an unactivated cubyl-H is comparable to NH (pKa
3
∼ 38), while that of a doubly activated cubyl-H, as in 1,3,5,7-
1
9
tetranitrocubane, is even higher (pK ∼ 21). Cubyl H atoms
a
5
6
Given this background, the crystal structures of 1,4-cubanedi-
are at least 10 -10 times more acidic than vinyl and phenyl
hydrogens. The active role of C-H‚‚‚O hydrogen bonds in
determining O-H‚‚‚O networks in the crystal structures of
terephthalic acid, fumaric acid, acrylic acid, 2,5-furandicar-
carboxylic acid (7) and 1,3,5,7-cubanetetracarboxylic acid
dihydrate (8) are of note.1
2,13
Diacid 7 is one of the three
structures in the CSD that contain catemer 6. Interestingly, the
syn and anti conformations are present in different (and
centrosymmetric) molecules rather than in the same diacid
molecule. In tetraacid 8, three of the four carboxylic groups
are in the syn conformation while one is in the anti conforma-
2
a,8a,14a
boxylic acid, and other acids is well-documented.
All of
this prompted us to synthesize some selected and related
2
0
cubanecarboxylic acids (10-16) and to explore their crystal
2
1
chemistry. The objective of this study was three-fold: (i) to
confirm if cubane derivatives form C-H‚‚‚O hydrogen bonds
and if so to clarify their specific structural role, (ii) to rationalize
the supposedly exotic crystal structure of diacid 7, and (iii) to
identify robust supramolecular synthons in crystalline cubane
(
8) (a) Leiserowitz, L. Acta Crystallogr. 1976, B32, 775. (b) Berkovitch-
Yellin, Z.; Leiserowitz, L. J. Am. Chem. Soc. 1982, 104, 4052.
9) By “catemer” is meant an infinite or finite noncyclic hydrogen bonded
(
pattern in which each carboxylic group is linked to two neighbours via
single O-H‚‚‚O (carbonyl) bonds. See ref 8a.
(10) (a) Allen, F. H.; Davies, J. E.; Galloy, J. J.; Johnson, O.; Kennard,
(14) (a) Bernstein, J.; Etter, M. C.; Leiserowitz, L. Structure Correlation;
B u¨ rgi, H.-B., Dunitz, J. D., Eds.; VCH: Weinheim, Germany, 1994; pp
431-507. (b) Herbstein, F. H. ComprehensiVe Supramolecular Chemistry;
MacNicol, D. D., Toda, F., Bishop, R., Eds.; Pergamon: Oxford, U.K.,
1996; Vol. 6, pp 61-83.
O.; Macrae, C. F.; Mitchell, E. M.; Mitchell, G. F.; Smith, J. M.; Watson,
D. G. J. Chem. Inf. Comput. Sci. 1991, 31, 187. (b) Allen, F. H.; Kennard,
O. Chem. Des. Autom. News 1993, 8, 1.
(11) The CSD (April 1998 version, 181 309 entries) contains 2067 metal-
atom free, nonionic, single-residue organic carboxylic acids. Of these, 1082
contain the syn-syn dimer and these could be automatically searched. A
manual search of the remaining 985 compounds revealed 67, 2, and 4 hits
for the syn-syn, anti-anti, and the syn-anti catemers, respectively. The
refcodes for the four syn-anti structures are CILDOQ, FIGMAJ, JUKVIU,
and SUHSET. Of these, CILDOQ is excluded from further discussion
because the syn and anti carboxylic acid groups are involved in numerous
other N-H‚‚‚O and C-H‚‚‚O hydrogen bonds. The number of syn-anti
catemeric structures that are of direct interest here is therefore three. The
report of the anti-anti catemer in the crystal structure of HCO2H‚HF is too
recent to be included in the April 1998 version of the CSD. See: Wiechert,
D.; Mootz, D.; Dahlems, T. J. Am. Chem. Soc. 1997, 119, 12665. In the
remaining 912 hits, the carboxylic group is hydrogen bonded to other basic
groups or is exclusively intramolecularly hydrogen bonded or forms closed
n-mers (n * 2). For another recent search of carboxylic acid hydrogen bond
patterns, see: Kolotuchin, S. V.; Fenlon, E. E.; Wilson, S. R.; Loweth, C.
J.; Zimmerman, S. C. Angew. Chem., Int. Ed. Engl. 1995, 34, 2654.
(15) (a) Eaton, P. E. Angew. Chem., Int. Ed. Engl. 1992, 31, 1421. (b)
Bashir-Hashemi, A.; Iyer, S.; Alster, J.; Slagg, N. Chem. Ind. 1995, 551.
(c) Marchand, A. P. Chem. Intelligencer 1995, 1, 8. (d) Hormann, R. E.
Aldrichim. Acta 1996, 29, 31.
(16) (a) Carell, T.; Wintner, E. A.; Bashir-Hashemi, A.; Rebek, J. Angew.
Chem., Int. Ed. Engl. 1994, 33, 2059. (b) Carell, T.; Wintner, E. A.; Rebek,
J. Angew. Chem., Int. Ed. Engl. 1994, 33, 2061.
(17) (a) Higuchi, H.; Ueda, I. Carbocyclic Cage Compounds; Osawa,
E., Yonemitsu, O., Eds.; VCH: New York, 1992; pp 217-247. (b) Eaton,
P. E.; Xiong, Y.; Gilardi, R. J. Am. Chem. Soc. 1993, 115, 10195. (c) Bashir-
Hashemi, A.; Hardee, J. R.; Gelber, N.; Qi, L.; Axenrod, T. J. Org. Chem.
1994, 59, 2132. (d) Head, N. J.; Rasul, G.; Mitra, A.; Bashir-Hashmi, A.;
Surya Prakash, G. K.; Olah, G. A. J. Am. Chem. Soc. 1995, 117, 12107.
(e) Bashir-Hashemi, A.; Li, J.; Gelber, N.; Ammon, H. J. Org. Chem. 1995,
60, 698. (f) Lukin, K. A.; Li, J.; Eaton, P. E.; Kanomara, N.; Hain, J.;
Punzalan, E.; Gilardi, R. J. Am. Chem. Soc. 1997, 119, 9591.
(18) Pedireddi, V. R.; Desiraju, G. R. J. Chem. Soc., Chem. Commun.
1992, 988.
(
(
12) Ermer, O.; Lex, J. Angew. Chem., Int. Ed. Engl. 1987, 26, 447.
13) Butcher, R. J.; Bashir-Hashemi, A.; Gilardi, R. D. J. Chem.
(19) Hare, M.; Emrick, T.; Eaton, P. E.; Kass, S. R. J. Am. Chem. Soc.
1997, 119, 9591.
Crystallogr. 1997, 27, 99.

1938 J. Am. Chem. Soc., Vol. 121, No. 9, 1999
KuduVa et al.
4
.34 (m, 6H, cubyl H). 13C NMR (50 MHz, CDCl
3
): δ 47.7 and 54.6
(
cubyl CH), 56.0 and 62.8 (cubyl C), 176.8 (CdO).
4
-Iodo-1-cubanecarboxylic Acid (12).2 To a degassed solution
0g
of the acid ester 13 (56 mg, 0.25 mmol) in benzene (12 mL) were
added Pb(OAc) (140 mg, 0.32 mmol) and I (152 mg, 0.6 mmol).
4
2
The resultant mixture was brought to reflux and irradiated with a 300
W tungsten lamp. After 3 h, the solution was cooled, filtered, washed
with aqueous NaHSO
the bulk of the benzene was removed. The methyl ester was hydrolyzed
to yield 55 mg (80%) of iodo acid 12. IR (cm ): 1670, 1636. H
3
solution (3 × 10 mL), and dried (MgSO
4
) and
acids as a prerequisite for future crystal engineering investiga-
tions.
-
1
1
NMR (200 MHz, CDCl ): δ 4.30-4.50 (m, 6H, cubyl H).
3
Experimental Section
Cubanecarboxylic Acid (14)20f was prepared in 50% yield from
acid ester 13.
In the early stages of this work, 1,4-bis(methoxycarbonyl)cubane
4-Phenyl-1-cubanecarboxylic Acid (15).20g To a degassed solution
of the acid ester 13 (112 mg, 0.5 mmol) in dry deoxygenated benzene
(9), a common starting material for 4-substituted-1-cubanecarboxylic
2
2
acids, was synthesized using the well-established Eaton and Cole
procedure, while later on, the commercial material (Aldrich)23 was used.
The cubanecarboxylic acids were characterized with NMR and IR
spectra and by the comparison of their spectral data with those of the
(12 mL) was added Pb(OAc) (280 mg, 0.625 mmol). The resultant
4
mixture was brought to reflux and irradiated with a 300 W tungsten
lamp. After 3 h, the solution was cooled, filtered, washed with NaHSO
3
2
1c 1
13
solution (3 × 10 mL), and dried (MgSO ) and the bulk of the benzene
corresponding methyl esters.
H NMR and C NMR were recorded
4
at 200 and 50 MHz on a Bruker ACF instrument. IR spectra were
recorded on a Jasco 5300 spectrophotometer. All reactions were carried
out in an inert atmosphere of dry nitrogen using standard syringe-septum
techniques with magnetic stirring. Workup means drying of the
removed to yield the methyl ester which was saponified to give 34 mg
-1
1
(30%) of phenylcubanecarboxylic acid (15). IR (cm ): 1680. H NMR
(200 MHz, CDCl
5H, phenyl H).
3
): δ 4.21-4.41 (m, 6H, cubyl H), 7.22-7.48 (m,
combined organic extracts with MgSO
4
, filtration, and concentration
4-(Carboxamido)-1-cubanecarboxylic Acid (16). To a solution of
acid ester 13 (56 mg, 0.25 mmol) in dry ether was added aqueous
ammonia solution (2 mL, 30%), and the mixture was stirred for 1 h to
of the crude residue in vacuo. All reagents and solvents were dried
and distilled prior to use. The synthesis of those acids from 10-16 is
detailed here, whenever there was a significant variation from the
published procedures.
-1
1
yield 43 mg (90%) of acid amide 16. IR (cm ): 1660, 1610. H NMR
(200 MHz, DMSO-d ): δ 4.00-4.10 (m, 6H, cubyl H).
6
4
-(Methoxycarbonyl)-1-cubanecarboxylic Acid (13)20f was pre-
pared in 80% yield according to the published procedure.
-Chloro-1-cubanecarboxylic Acid (10).20d The acid chloride of
3 (110 mg, 0.5 mmol), prepared by the treatment of acid 13 (110 mg,
.5 mmol) with SOCl , in dry CCl (2.5 mL), was added dropwise to
X-ray Data Collection and Crystal Structure Determinations.
X-ray data for acids 10-16 were collected on an Enraf-Nonius CAD-4
single-crystal diffractometer in the θ/2θ scan mode using graphite
monochromatized Cu KR radiation at room temperature. Structure
solution was performed by SIR92, and the RAELS program was used
for the refinement.24 A DEC Alpha-AXP workstation was used for these
calculations. All interatomic distance and related calculations were
carried out with Platon97.25 The acidic H atom positions were revealed
in the ordered acids 10 and 13, but only calculated positions were used
in the refinements because of irregularities that occurred when these
positions were refined. For the disordered acids, half H atoms were
placed in calculated positions.
4
1
0
2
4
an irradiated (300 W tungsten lamp) suspension of the anhydrous
sodium salt of N-hydroxypyridine-2-thione (90 mg, 0.6 mmol) and a
catalytic amount of DMAP in CCl
mixture was cooled and then poured into a separatory funnel, diluted
with Et O (5 mL), and washed with H
O (3 × 3 mL). The aqueous
layer was extracted with Et
O (3 × 3 mL). Workup afforded the methyl
ester whose saponification with methanolic NaOH yielded 50 mg (55%)
of chloro acid 10. IR (cm ): 1682, 1622. H NMR (200 MHz,
): δ 4.20-4.25 (m, 6H, cubyl H). 13C NMR (50 MHz, CDCl
CDCl ):
δ 45.9 and 54.0 (cubyl CH), 56.0 and 70.8 (cubyl C), 177.0 (CdO).
4
(5 mL) and refluxed for 3 h. The
2
2
2
-
1
1
Calculations. All calculations were carried out on Indigo Solid
Impact and Indy workstations from Silicon Graphics. In the Crystal
3
3
2
26
Packer and Diffraction Crystal (Cerius ) calculations, the Dreiding
2.21 force field was used.
2
0b
4
-Bromo-1-cubanecarboxylic Acid (11).
To a solution of
-bromopentacyclo[4.3.0.0 0 0 ]nonan-9-one-4-carboxylic acid eth-
ylene ketal (1.0 g, 3.3 mmol), prepared in 70% yield as described
2,5 3,8 4,7
1
Results and Discussion
2
0a
previously, in boiling CH
.7 mmol) was added dropwise a solution of Br
mmol) in CH Br (10 mL). When the addition was complete, the
mixture was heated at reflux for 3 h, cooled to room temperature, and
filtered. The CH Br was removed in vacuo to give a brown solid which
was extracted with hexane. Evaporation of hexane afforded 700 mg
75%) of 1,4-dibromopentacyclo[4.3.0.0 0 0 ]nonan-9-one ethylene
ketal. This ketal was hydrolyzed with 80% H SO followed by Favorskii
rearrangement with 50% KOH to yield 375 mg (50%) of bromo acid
2
Br
2
(25 mL) containing red HgO (0.8 g,
Cubane acids 10-16 were synthesized as described above.20,21c
Crystallization was attempted from a variety of organic solvents
(acetonitrile, benzene, chloroform, dichloromethane, dioxane,
ethyl acetate, formic acid, tetrahydrofuran, and mixtures of these
solvents). X-ray quality crystals were obtained from the solvents
listed in Table 1. The crystal structures of acids 7 and 10-16
are now described. The three halogenated cubanecarboxylic
acids 10-12, the acid ester 13, and the diacid 7 contain catemer
3
2
(0.80 g, 0.3 mL, 5
2
2
2
2
2,5 3,8 4,7
(
2
4
-
1
1
1
1. IR (cm ): 1684, 1623. H NMR (200 MHz, CDCl
3
): δ 4.29-
6
and are discussed first. In the mono- and phenyl-substituted
acids 14 and 15 described next, the common carboxy dimer 3
is present. Finally, we note that the acid amide 16 forms the
heterodimer 22. Computational results provide a better under-
standing of why different packing arrangements are adopted in
this family of cubanecarboxylic acids.
(
20) (a) Chapman, N. B.; Key, J. M.; Toyne, K. J. J. Org. Chem. 1970,
3
4
1
5, 3860. (b) Klunder, A. J. H.; Zwanenburg, B. Tetrahedron 1972, 28,
131. (c) Edward, J. T.; Farrell, P. G.; Langford, G. E. J. Am. Chem. Soc.
976, 98, 3075. (d) Barton, D. H. R.; Crich, D.; Motherwell, W. B.
Tetrahedron 1985, 41, 3901. (e) Moriarty, R. M.; Khosrowshahi, J. S. J.
Am. Chem. Soc. 1989, 111, 8943. (f) Eaton, P. E.; Nordari, N.; Tsanaktsidis,
J.; Upadhyaya, S. P. Synthesis 1995, 501. (g) Della, E. W.; Head, N. J. J.
Org. Chem. 1995, 60, 5303.
(24) (a) SIR92: Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano,
G.; Giacovazzo, C.; Guagliardi, A.; Polidori, G. J. Appl. Crystallogr. 1994,
27, 435. (b) RAELS: Rae, A. D. A Comprehensive Constrained Least
Squares Refinement Program, University of New South Wales, 1989.
(25) Platon97: Spek, A. L. Bijvoet Center for Biomolecular Research,
Vakgroep Kristal-en Structure-chemie, University of Utrecht.
(21) It may be noted that the crystal structures of some cubanecarboxylic
esters have been reported: (a) Cristiano, D.; Gable, R. W.; Lowe, D. A.;
Tsanaktsidis, J. Acta Crystallogr. 1995, C51, 1658. (b) Butcher, R. J.; Bashir-
Hashemi, A.; Gilardi, R. D. J. Chem. Crystallogr. 1995, 25, 661. (c)
Irngartinger, H.; Strack, S.; Gredel, F. Liebigs. Ann. 1996, 311, 315.
2
(
22) (a) Eaton, P. E.; Cole, T. W. J. Am. Chem. Soc. 1964, 86, 962. (b)
Eaton, P. E.; Cole, T. W. J. Am. Chem. Soc. 1964, 86, 3157.
23) Aldrich Chemical Co., Milwaukee, WI, 42,124-3, $88/g.
(26) Cerius Program: Molecular Simulations, 9685 Scranton Road, San
Diego, CA 92121-3752, and 240/250 The Quorum, Barnwell Road,
Cambridge CB5 8RE, U.K.
(

Cubanecarboxylic Acids
J. Am. Chem. Soc., Vol. 121, No. 9, 1999 1939
Table 1. Crystallographic Data of 4-Substituted-1-cubanecarboxylic Acids
space
acid group
density
(g/cm )
solvent used for
crystallization
melting
point (°C)
Rb
R
c
3
d
C
* e
76.8
a (Å)
b (Å)
c (Å)
â (deg)
Z
w
k
7a P2
/n 7.2512(6) 12.9050(12)
8.3031(5)
8.394(4)
14.269(6)
14.701(7)
8.252(2)
14.588(4)
11.056(2)
12.723(2)
90.993(6)
90.60(2)
113.13(2)
113.11(2)
90.724(9)
94.68(1)
123.448(9)
90
4
8
4
4
8
8
4
4
0.042 0.051
0.045 0.057
0.032 0.043
0.023 0.034
0.047 0.067
0.039 0.054
0.048 0.066
0.039 0.064
1.64
1.60
1.91
2.21
1.50
1.41
1.32
1.41
formic acid
226
1
1
1
1
1
1
1
10
11
12
13
14
15
16
P2
P2
P2
P2
P2
P2
/n 7.175(4)
/c 8.306(3)
/c 8.304(4)
/n 7.260(1)
/c 8.599(2)
/c 8.998(2)
25.233(8)
7.261(2)
7.341(2)
30.507(3)
11.131(2)
13.605(2)
7.127(1)
formic acid
chloroform
ethyl acetate
chloroform-ethyl acetate 154
chloroform
ethyl acetate-hexane
formic acid
197 (dec) 73.0
178-183 72.3
228 (dec) 72.5
73.6
120-123 71.5
166-168 68.8
215 (dec) 67.5
Pca2
1
9.944(1)
a
From ref 12. b Crystallographic reliability index, R ) ∑|F
). c Weighted residual R
2
2)1/2. d Calculated
o
- F
/V
c
|/∑F
o
for F
o
> 3σ(F
o
w
) (∑w∆ /∑wF
o
e
with the program BLOCKLS. Packing fraction C
molecule, and V is the total volume of the unit cell (calculated with the program Platon97).
c
k
* ) N(V
m
c
), where N is the number of molecules is the unit cell, V
m
is the volume of a single
25
Catemer Synthon 6 as a Recurring Pattern. The four
carboxylic acidsschloro acid 10, bromo acid 11, iodo acid 12,
and acid ester 13sare related in that they contain catemer 6 as
the common hydrogen bond pattern. In 4-chloro-1-cubanecar-
boxylic acid (10), the alternating, symmetry-independent syn
and anti carboxylic acid groups form the O-H‚‚‚O catemer
along [100]. Additionally, there are C-H‚‚‚O hydrogen bonds
between translation related molecules. These may be taken along
with catemer 6, to derive zigzag tapes that are constructed with
two nearly identical patterns, 17 and 18. Effectively, the larger
patterns 17 and 18 contain within them the smaller 6. In 17,
the C3-H of an anti molecule donates to the CdO group, while
in 18, the C3-H of a syn molecule donates to the carboxylic
OH group (Figure 1, Table 2). This subtle difference between
1
7 and 18 arises from the fact that the patterns contain both
syn and anti conformations and further because all carboxyl
groups are ordered. The Cl atoms fill the centrosymmetric voids
Cl‚‚‚Cl: 3.668(3) and 4.028(3) Å)2 created by the rest of the
7
(
packing and, in this manner, stabilize the overall crystal structure
(
Ck* ) 73%, Table 1). Successive (001) layers are linked
through C-H‚‚‚O hydrogen bonds (2.65-2.88 Å), not shown
in Figure 1b for clarity.
4
-Bromo-1-cubanecarboxylic acid (11) (Figure 2) and 4-iodo-
-cubanecarboxylic acid (12) (Table 2) are isostructural and also
adopt the catemer structure 6, but here, the carboxylic acid
groups are disordered (Table 3). Since the CdO and the
C-OH groups are now indistinguishable, 17 and 18 merge into
a single pattern. The view down [100] in bromo acid 11 and
iodo acid 12 (not shown) is identical to that down [001] in chloro
acid 10, with the minor difference that, while in 10 the carboxy
1
Figure 1. Crystal structure of 4-chloro-1-cubanecarboxylic acid (10).
(a) View down [001] showing the layer with the zigzag arrangement
of synthons 17 and 18. Notice the type-I contact between the Cl atoms
of inversion-related molecules. (b) View down [100] showing the
packing of layers. (c) Space-filling diagram of the layer adjacent to
that shown in (a) with atoms drawn acccording to their van der Waals
radii. Notice that the Cl atoms fill the voids created by the catemer
structure.
28
(27) In the type-I centrosymmetric geometry, it is possible that the
inversion-related halogen atoms merely close pack rather than participate
in specific polarization-driven interactions. (a) Pedireddi, V. R.; Reddy, D.
S.; Goud, B. S.; Craig, D. C.; Rae, A. D.; Desiraju, G. R. J. Chem. Soc.,
Perkin Trans. 2 1994, 2353. (b) Navon, O.; Bernstein, J.; Khodorkovsky,
V. Angew. Chem., Int. Ed. Eng. 1997, 36, 601.
groups stack on themselves (Figure 1b), they lie on the close-
2
7
packed Br‚‚‚Br and I‚‚‚I atoms of the next layer in 11 and 12
Figure 2b). In addition to the hydrogen bonds shown in Figure
, there are C-H‚‚‚O bonds between the cubyl C3-H and the
carboxyl O-atom and a long C-H‚‚‚Br (3.108 Å, 169.5°) and
(
2
(
28) (a) Diederich, D. A.; Paul, I. C.; Curtin, D. Y. J. Am. Chem. Soc.
974, 96, 6372. (b) Goud, B. S.; Pathaneni, S. S.; Desiraju, G. R. Acta
Crystallogr. 1993, C49, 1107.
1

1940 J. Am. Chem. Soc., Vol. 121, No. 9, 1999
KuduVa et al.
Table 2. Geometry of O-H‚‚‚O and C-H‚‚‚O Interactions in the
Crystal Structures of Acids 10-16
acid
interaction
d (Å)a
D (Å)a
θ (deg)a
1
0
a
b
c
d
a
b
c
a
b
c
a
b
c
d
e
f
O-H‚‚‚O
O-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
1.664
1.714
2.373
2.526
2.623
2.629
3.40
164.2
153.2
157.4
152.1
3.52
b
11
12
13
O-H‚‚‚O
2.698
2.573
3.565
2.696
2.591
3.66
b
O-H‚‚‚O
C-H‚‚‚O
2.547
156.4
b
O-H‚‚‚O
b
O-H‚‚‚O
C-H‚‚‚O
O-H‚‚‚O
O-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
2.647
1.665
1.670
2.596
2.447
2.61
2.514
2.746
2.747
2.646
2.697
155.6
170.4
160.1
152.5
158.7
155.6
160.7
136.8
134.9
147.2
144.5
2.639
2.616
3.591
3.478
3.624
3.554
3.612
3.594
3.605
3.634
2.614
2.645
3.784
3.894
3.747
2.643
3.873
3.638
3.611
3.972
2.604
2.854
2.922
3.692
3.484
g
h
k
l
b
14
15
16
a
b
c
d
e
a
b
c
d
e
a
b
c
d
e
O-H‚‚‚O
O-H‚‚‚O
b
C-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
O-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚π
C-H‚‚‚O
O-H‚‚‚O
N-H‚‚‚O
N-H‚‚‚O
C-H‚‚‚O
C-H‚‚‚O
2.789
2.891
2.830
1.660
2.819
2.826
2.679
2.944
1.627
1.865
1.994
2.754
2.482
152.7
154.2
142.4
179.2
164.5
131.8
143.0
158.6
171.9
166.0
151.7
144.9
153.3
Figure 2. Crystal structure of 4-bromo-1-cubanecarboxylic acid (11).
(
a) Layer containing synthons 17 and 18 and the inversion-related
Br‚‚‚Br contacts. Notice the similarity with Figure 1a. (b) View down
010] to show the stacking of Br atoms and carboxylic acid groups in
successive layers. Contrast this with Figure 1b where the stacking is
Cl‚‚‚Cl and CO H‚‚‚CO H.
[
2
2
Table 3. Order-Disorder in Acids 7-16
acid
∆d (Å)a
∆θ (deg)b
acid
∆d (Å)a
∆θ (deg)b
a
For the definitions of d, D, and θ, see ref 6d. All H atom positions
7
0.095
0.089
0.088
3.4
9.0
3.3
8.0
0.8
1.1
13
0.085
0.089
0.002
0.006
0.046
0.100
0.7
4.2
1.8
1.0
3.5
are normalized (Rowland, R. S.; Taylor, R. J. Phys. Chem. 1996, 100,
384). The carboxylic acid groups are disordered.
b
7
1
0
14
0
.076
C-H‚‚‚I (3.157 Å, 169.6°) contact between the cubyl C2-H
group and the halogen atoms of the next layer.
1
1
1
2
0.020
0.008
15
16
10.0
The carboxylic acid group in 4-(methoxycarbonyl)-1-cuban-
ecarboxylic acid (13) (Figure 3) is ordered and 17 and 18 run
along [100], as in chloro acid 10 (Table 2). Further, because of
the carbomethoxy CdO group, translation related syn and anti
molecules are connected by cyclic patterns 19 and 20 formed
solely with cubyl C-H‚‚‚O hydrogen bonds. So, one may
analyze the hydrogen bonded layer parallel to (001) as consti-
tuted with different synthons depending on how one dissects
the structure: (i) synthons 17 and 18 and zigzag C-H‚‚‚O
chains (interactions e and f) or (ii) synthon 6 accompanied by
a
. b ∆θ ) θ
∆
d ) d
1
- d
2
1
2
- θ . For more details, see ref 28.
overlapping synthons. However, one may state that synthons
7 and 18 combine compactness in size with completeness of
structural information, and in this sense, they may be regarded
as effective descriptors of the crystal structure.
It may be noted that the carboxylic acid group is ordered in
acids 10 and 13 while it is disordered in 11 and 12. It is unlikely
that there is dynamic disorder along individual catemers since
this would involve cooperative proton transfer. A more plausible
explanation for the disorder is that it is static in nature and
1
1
9 and 20 (Figure 3a). Thus, there is an element of subjectivity
29
involves translationally related catemers. The crystal structures
of the ordered acids 10 and 13 and the disordered acids 11 and
1
2 offer a clue to the cause of order/disorder. In the former
cases, catemer 6 is nonplanar and is stacked along [001] without
offset (Figures 1b and 3b). In the latter, the catemer is planar
and is stacked between the Br and I atoms of adjacent layers
8
a
(
Figure 2b). It should be noted here that the assignment of
structures as ordered/disordered is not based on the H atom
positions but on the particular intramolecular C-O distances
2
(
29) This was verified with lattice energy calculations (Cerius ). Pairs
of catemers were constructed with opposite senses, for the ordered and
disordered acids. The difference in hydrogen bond energy between the two
alternative catemer pair arrangements (parallel versus antiparallel) is large
in deciding which set of interactions constitutes the primary
structural motif. This is generally true in complex crystal
structures wherein a given interaction may form a part of several
(
∼10 kcal/mol) for the ordered acids, while it is very small for the disordered
acids (<0.1 kcal/mol).

Cubanecarboxylic Acids
J. Am. Chem. Soc., Vol. 121, No. 9, 1999 1941
So, larger synthons are potentially more useful than smaller ones
(17 and 18 as opposed to 6). But, as synthon size increases,
occurrence becomes less frequent and, in this sense, the twin
criteria for identifying useful synthons seem to be contradictory.
Despite this, it should be noted that, between these extremes of
small size and numerous occurrences and large size and
infrequent occurrences, there lies an optimal region wherein
the maximum structural information is contained in a synthon
of minimum size. It is in this domain then that the visualization
of supramolecular synthons and comparison of crystal structures
is most effectively accomplished.
To summarize, the primary structural motifs, synthons 17 and
1
8, are characterized by a combination of the alternating syn
and anti CO2H groups and support from the enhanced acidity
of the cubyl C-H donors. In this light, the crystal structure of
diacid 7 also stands rationalized. It may simply be accounted
for in terms of the symmetrical occurrence of synthons 17 and
18 on either side of the cubyl skeleton (Figure 4b). The recurring
catemer synthon also determines the repeat distance of ca. 7.2
Å between successive cubane molecules in the five monoclinic
crystal structures (7, a ) 7.2512(6) Å; 10, a ) 7.175(4) Å; 11,
b ) 7.261(1) Å; 12, b ) 7.341(2) Å; 13, a ) 7.260(1) Å; Table
1
). From the above results, it appears that this structure type is
Figure 3. Crystal structure of 4-(methoxycarbonyl)-1-cubanecarboxylic
acid (13). (a) View down [001] to show the zigzag arrangement of
insensitive to substitution changes at the 4-position as long as
the groups are of a similar bulk (R ) Cl, Br, I, CO2Me) or
have an identical hydrogen bond pattern (R ) CO2H). This led
us to examine the crystal structure of cubanecarboxylic acids
with very small (R ) H, 14) and very large (R ) Ph, 15)
substituents.
synthons 17 and 18. Notice that the inversion-related CO
play a space-filling role similar to that of the halogen atoms in 10-12.
b) Stacking of the carboxylic acid and ester groups in successive (001)
2
Me groups
(
layers.
and angles (Table 3). The classical work of Paul and Curtin28a
on carboxylic acid disorder justifies such a procedure.
The assignment of the monoclinic space group P21/n for acids
, 10, and 13 may also be noted. In these cases, there are two
7
The repeated occurrence of the otherwise rare synthon 6 in
the family of carboxylic acids under study here is quite likely
the result of fortification of the catemer by a weak hydrogen
bond formed by the acidic cubyl C-H group. According to such
an argument, if such a favorable C-H‚‚‚O bond were absent,
the catemer structure might not have been observed. In this
connection, the crystal structures of 4-chlorophenylpropiolic acid
independent molecules in the asymmetric unit and the â angles
are 90.993(6)°, 90.60(2)°, and 90.724(9)°, respectively (Table
1
). These symmetry-independent molecules are related by
pseudo-2-fold symmetry along [001] with the pseudo-2-fold axes
lying halfway between the inversion centers. These crystal
structures thus have pseudo orthorhombic symmetry {P21/c,
P21/n, P21/b} or simply Pcnb.
(21a) and 4-bromophenylpropiolic acid (21b), reported earlier
Carboxy Dimer Synthon 3 in Acids 14 and 15. Cuban-
ecarboxylic acid 14 adopts the normal dimer 3. The CO2H group
2
8
is disordered, and there are two molecules, A and B, in the
asymmetric unit (Figure 5). Unusually, the dimers are of the
A‚‚‚B type (O‚‚‚O: 2.614, 2.645 Å, Table 2). The dimers are
staggered so that a cubyl group lies above an adjacent dimer.
Layers parallel to (100) are linked through C-H‚‚‚O hydrogen
bonds between inversion-related dimers. The symmetry-
independent A and B molecules form different types of
3
1
C-H‚‚‚O bonds.
In 4-phenyl-1-cubanecarboxylic acid (15), the dimers lie on
inversion centers (Figure 6a). The participation of phenyl and
cubyl C-H donors in C-H‚‚‚O bonding with the carboxy O
atom leads to a bifurcated pattern. The (010) layers are formed
by our group,30 are also of interest (Figure 4a). These are the
two other acids in the literature that show the syn-anti catemer
32
with cubyl C-H‚‚‚O and C-H‚‚‚π(Ph) hydrogen bonds
(Figure 6b, Table 2). Consideration of the crystal structures of
6
and here too the catemer is strengthened by a C-H‚‚‚O bond,
1
4 and 15 suggests that there is a limit to which the catemer
2
but now from a phenyl C(sp )-H group.
structure will manifest itself in this family of acids. As long as
the steric requirements of the 4-substituent group are compatible
with the O-H‚‚‚O catemer 6, it is observed. However, when
the substituent group is too small or too large, the dimer is
adopted because its formation is largely independent of the size
The efficacy of a supramolecular synthon as an indicator of
crystal packing arises from its frequency of occurrence.
However, another criterion that should be used while assessing
the usefulness of synthons is that of size. Synthons represent a
carryover of structural information between crystal structures,
and as their size increases, so does their information content.
(31) The packing features in acid 14 show some resemblance to those
found in 1,4-dicubyl-1,3-butadiyne. Eaton, P. E.; Galoppini, E.; Gilardi, R.
J. Am. Chem. Soc. 1994, 116, 7588.
(30) (a) Desiraju, G. R.; Murty, B. N.; Kishan, K. V. R. Chem. Mater.
1
2
990, 2, 447. (b) Goud, B. S.; Desiraju, G. R. Acta Crystallogr. 1993, C49,
92.
(32) Madhavi, N. N. L.; Katz, A. K.; Carrell, H. L.; Nangia, A.; Desiraju,
G. R. Chem. Commun. 1997, 1953.

1942 J. Am. Chem. Soc., Vol. 121, No. 9, 1999
KuduVa et al.
2
Figure 4. (a) Crystal structure of 4-(bromophenyl)propiolic acid 21b to show the supportive role of the C(sp )-H‚‚‚O hydrogen bond to the catemer
synthon 6. (b) Crystal structure of 1,4-cubanedicarboxylic acid (7) showing the symmetrical arrangement of synthons 17 and 18 on both sides of
the cubyl residue. Compare the two figures.
Figure 5. Packing diagram of the crystal structure of cubanecarboxylic
acid 14 to show O-H‚‚‚O and C-H‚‚‚O hydrogen bonds. The dimers
are formed by symmetry-independent molecules. Notice that one of
the cubyl C-H atoms forms a bifurcated hydrogen bond (sum of angles
at the donor atom ) 353.1°).
8a
and shape of the substituent group. In addition to the supportive
role of the C-H‚‚‚O hydrogen bonds in 10-13, the formation
of the catemer in these structures also depends on size
complementarity of the hydrophobic groups that enables them
to fill the voids in the structure.
Figure 6. Crystal structure of 4-phenyl-1-cubanecarboxylic acid (15).
a) Formation of the centrosymmetric carboxy dimer 3 fortified by
auxiliary cubyl and phenyl C-H‚‚‚O hydrogen bonds. (b) View down
(
[010] showing the connections through C-H‚‚‚O and C-H‚‚‚π
interactions between the (100) layers.
The nonformation of the catemer structure in cubanecarboxy-
lic acid 14 was next investigated computationally. The Cl atoms
in the observed crystal structure of chloro acid 10 were replaced
by H atoms, and the structure was minimized (Crystal Packer,
Cerius ) to obtain a putative catemer structure. The calculated
structure contains voids in the hydrophobic region because the
rigid cubyl groups are unable to close pack efficiently. Similarly,
if phenylcubanecarboxylic acid (15) were to have a catemer
structure with a translational repeat distance of ca. 7.2 Å, the
bulky phenyl groups will approach too close to one another,
resulting in unfavorable repulsions.33 Having examined the role
of size- and shape-related features that favor specific
O-H‚‚‚O and C-H‚‚‚O hydrogen bond patterns in cubanecar-
boxylic acids, we decided to introduce a functional group that
has a strong and distinct hydrogen bonding capability of its own.
Thus, the 4-carboxamide derivative (R ) CONH2, 16) was
examined finally.
NbO-Type Network in the Crystal Structure of Acid
Amide 16. The crystal structure of 4-(carboxamido)-1-cuban-
ecarboxylic acid (16) is non-centrosymmetric (Pca21) (Table
1). The dominant hydrogen bond pattern is the heterodimer
2
26
(
33) Interestingly, it was found that when syn and anti conformers were
2
input together in the Polymorph Predictor program (Cerius ), the unobserved
catemer structure was not generated for either 14 or 15. This computation
provides some corroboration for the occurrence of dimer structure in 14
and 15. For details on generating structures using the Polymorph Predictor,
see: (a) Leusen, F. J. J. J. Cryst. Growth 1996, 166, 900. (b) Payne, R. S.,
Roberts, R. J., Rowe, R. C.; Docherty, R. J. Comput. Chem. 1998, 19, 1.
(
c) Mooij, W. T. M.; van Eijck, B. P.; Price, S. L.; Verwer, P.; Kroon, J.
J. Comput. Chem. 1998, 19, 459. For an early computational study on the
nonexistence” of a proposed structure, see: Hagler, A. T.; Bernstein, J. J.
Am. Chem. Soc. 1978, 100, 6349.
between the carboxylic acid and carboxamide groups. Het-
erodimer 22 is commonly found in acid-amide complexes as
well as in molecules containing both these functional groups.34
“

Cubanecarboxylic Acids
J. Am. Chem. Soc., Vol. 121, No. 9, 1999 1943
The formation of such a heterodimer as opposed to acid‚‚‚acid
and amide‚‚‚amide homodimers may be argued on the following
grounds: (i) The principle that a good hydrogen bond donor
will seek out the best acceptor atom.35 Thus, the strongest donor
(
acid OH) hydrogen bonds to the strongest acceptor (amide
CdO) while the slightly weaker donor (amide NH) bonds to
the weaker acceptor group (acid CdO). (ii) To avoid inter-
molecular lone-pair repulsion between the hydroxyl and carbonyl
O atoms that occurs in hydrogen bonded chains built from
homodimers and connected through N-H‚‚‚O hydrogen bonds.
In the heterodimer arrangement, the distance between neighbor-
ing N-H groups hydrogen bonded to the same amide O atom
increases and consequently the lone-pair repulsion is mini-
mized.8
a,36
In acid amide 16, heterodimers 22 are formed between 21
related molecules to produce ribbons along [012] and [01 2h ].
The amide groups of these heterodimers are in turn connected
through N-H‚‚‚O and C-H‚‚‚O hydrogen bonds with the
3
7,38
a-glide related molecules, as shown in 23.
Visualizing the
crystal structure of 16 in terms of networks,1
d,5b
with the
molecules represented as nodes and the supramolecular synthons
as node connectors, one can discern the similarity between the
four-connected three-dimensional architecture of 16 and the NbO
3
9
network. This is illustrated as a stereoview in Figure 7. To
our knowledge, acid amide 16 is the first all-organic molecule
whose crystal structure has been reported to contain the NbO
network. Coordination polymers have been recently found that
exhibit the NbO architecture.40 In 16, however, there is two-
fold interpenetration with the networks being linked through a
C-H‚‚‚O hydrogen bond (2.482 Å, 153.3°).
A pertinent issue is the extent to which the abovementioned
arguments are valid if polymorphism were to be widespread in
the family of structures studied here, especially if the same acid
crystallizes in both dimer and catemer forms. The powder X-ray
diffraction pattern of 1,4-cubanedicarboxylic acid (7) recrystal-
lized from formic acid was recorded. The powder pattern closely
matches the pattern simulated from the observed crystal structure
2
26
using Diffraction Crystal (Cerius ), confirming that the crystals
of diacid 7 that were analyzed by X-ray diffraction represent
the bulk sample. Interestingly, when diacid 7 was recrystallized
from a mixture of ethyl acetate and hexane, a solvent system
very different from formic acid, the crystals still have the same
structure. These experiments suggest that the observed catemer
structure is the dominant form in these cases. Solubility
considerations prevented further recrystallization experiments
from other solvents.
Conclusions
Some selected 4-substituted-1-cubanecarboxylic acids have
been synthesized and their packing characteristics examined.
(
34) (a) Leiserowitz, L.; Nader, F. Acta Crystallogr. 1977, B33, 2719.
(
b) Chang, Y.-L.; West, M.-A.; Fowler, F. W.; Lauher, J. W. J. Am. Chem.
Soc. 1993, 115, 5991. (c) Wash, P. L.; Maverick, E.; Chiefari, J.; Lightner,
D. A. J. Am. Chem. Soc. 1997, 119, 3802.
(
35) Etter, M. C. Acc. Chem. Res. 1990, 23, 120.
(36) Leiserowitz, L.; Hagler, A. T. Proc. R. Soc. London 1983, A388,
1
33.
37) For the crystal structure of N,N′-dibenzyl-1,4-cubanedicarboxamide,
see ref 2b.
Figure 7. Stereoviews of the crystal structure of 4-(carboxamido)-1-
cubanecarboxylic acid (16). (a) Actual structure showing heterodimer
(
22, N-H‚‚‚O and C-H‚‚‚O hydrogen bonds. The heterodimer ribbons
(38) This and other synthons may also be represented in the graph set
notation (Bernstein, J.; Davis, R. E.; Shimoni, L.; Chang, N.-L. Angew.
along [012] and [01 2h ] are identical. The N-H‚‚‚O and C-H‚‚‚O
interactions run along [001]. (b) Structure depicted as a four-connected
NbO network. The molecules are reduced to spheres and the supra-
molecular synthons to double lines. (c) Two-fold interpenetration of
networks. The two networks are connected through C-H‚‚‚O hydrogen
bonds (not shown for clarity). The spheres in the two networks are
shaded differently.
2
Chem., Int. Ed. Engl. 1995, 34, 1555): 4-6 as C(4), 3 and 22 as R2 (8),
3
2
1
1
7 and 18 as R3 (12), 19 and 20 as R2 (10), and 23 as R2 (7).
(
39) Wells, A. F. Structural Inorganic Chemistry, 4th ed.; Clarendon
Press: Oxford, U.K., 1975.
40) (a) Power, K. N.; Hennigar, T. L.; Zaworotko, M. J. Chem. Commun.
998, 595. (b) Carlucci, L.; Ciano, G.; Macchi, P.; Proserpio, D. M. Chem.
Commun. 1998, 1837.
(
1

1944 J. Am. Chem. Soc., Vol. 121, No. 9, 1999
KuduVa et al.
Of the seven crystal structures analyzed, four contain the unusual
syn-anti O-H‚‚‚O catemer 6. This pattern is extremely rare in
general (3 out of 2067 carboxylic acids, of which one is diacid
Government of India (SP/S1/G19/94), and cooperation from
Molecular Simulations, Cambridge, England. S.S.K. thanks the
University Grants Commission, Government of India, for
fellowship support.
7) but is found to be the dominant pattern in the particular family
of acids studies here. The formation of synthon 6 is attributed
to its stabilization from C-H‚‚‚O hydrogen bonds formed by
the acidic cubyl C-H donors and the carboxyl O-acceptor
atoms. This study shows that two new synthons, 17 and 18
constructed with a combination of strong and weak hydrogen
bonds are the primary structural motifs that determine the
supramolecular architecture in these acids. The identification
of these synthons is a prerequisite for the crystal engineering
of cubanecarboxylic acids toward nanostructures with well-
defined architectures and functions.
Supporting Information Available: ORTEP diagrams and
tables giving crystal data and structure refinement, atomic
coordinates, isotropic and anisotropic displacement parameters,
and bond lengths and angles for 10-16 (PDF). An X-ray
crystallographic file, in CIF format, is also available. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. G.R.D. and A.N. acknowledge financial
support from the Department of Science and Technology,
JA981967U