Seeking structural repetitivity in systems with interaction interference: Crystal engineering in the gem-alkynol family

Article abstract of DOI:10.1039/a908233f

Synthon repetitivity has been demonstrated in a pair of gem-alkynols, despite the high degree of interaction interference typical of this family of compounds.

Full text of DOI:10.1039/a908233f

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Seeking structural repetitivity in systems with interaction
interference: crystal engineering in the gem-alkynol family
N. N. Laxmi Madhavi,a Clair Bilton,b Judith A. K. Howard,*b Frank H. Allen,c Ashwini Nangiaa
and Gautam R. Desiraju*a
L e t t e r
a School of Chemistry, University of Hyderabad, Hyderabad 500 046, India.
E-mail: grdch=uohyd.ernet.in
b Department of Chemistry, University of Durham, South Road, Durham, UK DH1 3L E
c Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, UK CB2 1EZ
Received (in Montpellier, France) 12th October 1999, Accepted 22nd November 1999
Synthon repetitivity has been demonstrated in a pair of gem-
alkynols, despite the high degree of interaction interference
typical of this family of compounds.
sity of the more extended patterns formed with these inter-
actions is shown in Scheme 1 by the synthons that occur more
or less frequently in this group.
These 94 gem-alkynols are a diverse group, though the
majority of them (61) are steroids with moiety 1 at the C17
position.° The list also contains other disparate compounds,
such as 4 phenyl-rich molecules and 6 molecular complexes,
that have been investigated with considerations other than
crystal engineering in mind. The lack of structural repetitivity
among these compounds may arise from the close juxtaposi-
tion of two hydrogen bond donors and two acceptors. In this
sterically hindered situation, and also with their incorporation
into cooperative networks, the four possible interactions, OÈ
HÉ É ÉO, CÈHÉ É ÉO, OÈHÉ É Ép and CÈHÉ É Ép, become competi-
tive.1 The packing adopted by any particular compound then
becomes extremely sensitive to other molecular features. In
practice, the unusually high level of interaction interference
generates several quite di†erent networks (Scheme 1), so that
it is not at all easy to establish the moleculeÈsupermolecule
correspondences3 that are so important in crystal engineering.
The problem, then, is quite simpleÈhow does one predict that
a particular gem-alkynol will form a particular hydrogen bond
pattern?
Crystal engineering methodologies attempt to identify
common patterns in a series of crystal structures, so as to
understand them in terms of mutual interplay between partic-
ular intermolecular interactions.1,2 Since interactions arise
from molecular functionalities, one of the important aims of
crystal engineering is, in e†ect, to establish correspondences
between molecular and crystal structures.3 This aim, however,
is challenged by a group of 90 or so compounds with a
geminal ethynyl hydroxy moiety, 1. The 94 published
structures¤ in this category exhibit a bewildering variety of
intermolecular interaction patterns.1,4,5 Analysis of these
structures showed 16 OÈHÉ É ÉO, 28 CÈHÉ É ÉO, 6 OÈHÉ É Ép and
1
4 CÈHÉ É Ép contacts in the normal ranges for these inter-
actions” [Cambridge Structural Database (CSD), Version
.16, October 1998, 190 307 entries]6 and where all donor and
acceptor atoms originate exclusively from moiety 1. The diver-
5
Given that the molecular structures of the 94 CSD exam-
ples are diverse and sometimes complex, it was felt that the
Ðrst step in the understanding of crystal packing of the gem-
alkynols would be to simplify the kind of molecule being
Scheme 1 Some common supramolecular synthons in the crystal
structures of gem-alkynols.
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1(b) shows that each of the C(sp2)ÈH groups is important in
studied. About half of these CSD compounds (45) contain
other functional groups that are capable of acting as strong
hydrogen bond donors and acceptors, leading to an unneces-
sary and avoidable complication in a system as fragile as the
present one. The fact that 72 of the crystal structures contain
single enantiomers is a further complication in that centro-
symmetrical packing patterns are precluded in these cases.Ò
Accordingly, trans-1,4-diethynyl-1,4-dihydroxy-2,5-cyclohexa-
diene, 2, was identiÐed as a starting point in the crystal engin-
eering exercise. The symmetry of the molecule virtually dic-
tates a centrosymmetric packing, while the small size and the
absence of functional groups other than the alkynol fragment
was expected to result in further simpliÐcation, leading to a
packing that could be rationalised and subsequently repeated
in another derivative.
the densely packed layer parallel to (100). The structure of
alkynol 2 is therefore another example of heavy structural
interference in this family. The various functional groups
(hydroxy, ethynyl, alkenic) are intimately involved with one
another and they also interact with the hydrocarbon residues.
Disturbing any of these interactions will result in a total
change in the structure, so that substitutional manipulation at
any of the alkenic positions was not expected to preserve this
structure type.
Attention shifted therefore to the trans-dibenzoalkynol 3,
prepared analogously from 9,10-anthraquinonep and whose
crystal structure** is shown in Fig. 2. There are two symmetry
independent half-molecules, each lying on a distinct inversion
centre. The alkynol groups from these two sets of molecules
result in the centrosymmetric cooperative synthons, 4 and 5.
Both these overlapping synthons involve both of the
symmetry-independent molecules (A and B in the scheme), but
Alkynol 2 was prepared by the addition of excess TMSÈ
C3CÈLi to 1,4-benzoquinone, hydrolysis of the TMS group
with methanolic KOH, and puriÐcation by column chroma-
tography followed by recrystallisation from ethyl acetate.p
Fig. 1 shows that the crystal packing is, as expected, simple.**
while 4 is constituted with OÈHÉ É ÉO (1.90 A
HÉ É ÉO (2.07 A, 163¡) hydrogen bonds, 5 is constituted with
CÈHÉ É ÉO (2.07 A, 163¡) and CÈHÉ É Ép (2.84 A, 157¡) bonds.
Ž , 160¡) and CÈ
Ž
InÐnite cooperative OÈHÉ É ÉOÈHÉ É ÉOÈHÉ É É (d 2.12 A
chains are formed along [010] while CÈHÉ É ÉO (2.39 A
and CÈHÉ É Ép (2.90 A, 127¡) hydrogen bonds are formed in the
100) plane. The long HÉ É ÉO distance may be noted. Though
Ž
, h 163¡)
Ž
Ž
Ž
, 142¡)
The synthon arrangement is detailed in Fig. 2(a). There are
several encouraging features here: (1) synthon 4 had pre-
viously been noted by us in the crystal structure of
2-ethynyladamantan-2-ol,7 where it is also formed from por-
tions of two symmetry-independent molecules and this is the
Ðrst instance of structural repetitivity of a major synthon in
this family between two compounds with widely di†erent sub-
Ž
(
the structure is straightforward, it was hardly predictable. Fig.
6
stituent groups; (2) synthons 4 and 5 lie within (110) and form
a sheet structure that consists exclusively of strong and weak
Fig. 1 (a) Crystal structure of alkynol 2. Note the inÐnite coopera-
tive OÈHÉ É ÉOÈHÉ É É chains formed between b-glide related molecules.
6
Fig. 2 (a) Crystal structure of alkynol 3 in (110), showing the cyclic
(
b) Densely packed layer structure parallel to (100) in the structure of
synthons 4 and 5. Notice the elaborate cooperative network of strong
and weak hydrogen bonds. (b) Stereoview of the crystal structure of 3
down [001], showing the interdigitation of the anthryl residues. The
view is perpendicular to that shown in (a).
2
. Notice the CÈHÉ É ÉO and CÈHÉ É Ép hydrogen bonds. Replacement
of any of the alkenic H atoms with a substituent is expected to change
the structure.
2
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Nevertheless, the manner of interdigitation of benzo rings in
hydrogen bonds; (3) the fused phenyl rings protrude from
either side of the hydrogen bonded sheet and interdigitate
with the corresponding rings in the adjacent sheets. This is
shown in Fig. 2(b). The hydrogen bonded and close-packed
domains here are structurally orthogonal, and clearly the
interaction interference between the hydrogen bonding groups
and the fused ring hydrocarbon portions of alkynol 3 is
minimal.¤¤
One may now extrapolate to the unsymmetrical trans-
benzoalkynol, 6, which was prepared similarly from 1,4-naph-
thoquinonep and the structure of which is shown in Fig. 3.**
The extended hydrogen bonded sheet seen in 3 (with overlap-
ping synthons 4 and 5) is retained intact here. Because the
molecule lacks a centre of symmetry, this is possible with two
3 and 6 is very similar. In general, one may expect that the
substituted benzo rings in compounds 7 and 8 (R \ simple
substituent groups) might also interdigitate in the same way.
Accordingly, we predict that other members of this family are
likely to adopt similar crystal structures, thereby leading to
structural repetitivity.
It is noteworthy that a fairly abstruse hydrogen bonded
network is repeated in alkynols 3 and 6. Anticipation of the
structure of 6 was possible because of the orthogonal and
non-interfering arrangement of hydrogen bonding and phenyl-
phenyl interactions in 3. This situation is similar to the crystal
structure of 4-aminophenol3a in which the OHÉ É ÉNH and
2
phenylÉ É Éphenyl interactions are insulated from each other
symmetry-independent molecules (P2 /c, Z \ 8) and with
and in contrast to the structures of 2- and 3-aminophenol,3b
which show a high degree of interaction interference. Inter-
action orthogonality is of key importance in establishing the
beginnings of structural repetitivity in systems where severe
structural interference is likely.
1
each molecule situated on a general position. The crystal
structures of alkynols 3 and 6 are actually very closely related,
with a minor di†erence in the disposition of the fused benzo
rings. In 6, the rings are situated on the same side of the
hydrogen bonded sheets so that one Ðnds aromaticÈaromatic
interdigitation alternating with sheetÈsheet close-packing. In
3
, the molecules lie on inversion centres so that interdigitation
occurs on both sides of the molecular plane. These alternative
modes of interdigitation may be compared by examining Fig.
Notes and references
¤ These structures were obtained from the CSD. Screens 57 (organic
only), [55 (charged species removed), 153 (3D coordinates present)
were applied; duplicate hits were removed manually.
2(b) and 3(b).
”
1
The d,h ranges are 1.7È2.1, 140È180; 2.0È2.9, 110È180; 2.0È2.9, 110È
80; and 2.5È3.1 A, 110È180¡, respectively. All OÈH and CÈH dis-
Ž
tances are neutron-normalised. That the number of these interactions
64) is less than the number of compounds (94) is because many of the
(
molecules have hydrogen bonding donor and acceptor groups other
than those in moiety 1.
°
Some trivial packing similarities do exist in the steroid sub-category
but these isostructuralities may be largely ascribed to the steroid
skeleton itself with the role of the 17-substituents (hydroxy and
ethynyl) being innocuous to supportive at best.
Ò Whether this is, or is not, advantageous from the viewpoint of
crystal engineering is still polemical. However, the work of
Kitaigorodskii8 would tend to suggest that the anticipation of the
crystal packing of a centrosymmetrical molecule is easier because a
centre of symmetry would almost always be found in the crystal.
p Spectroscopic data. 2: 1H NMR d 6.10 (s, 4H), 2.55 (s, 2H), 1.70 (br
s, 2H); IR (cm~1) 3468, 3267, 2924, 2102, 1413, 1367, 1221, 1086, 1041,
1
003, 916, 787, 686; mp 179È180 ¡C (sublimes). 3: 1H NMR d 8.10
(
dd, J 8, 3 Hz, 4H), 7.41 (dd, J 8, 3 Hz, 4H), 2.90 (s, 2H), 2.80 (s, 2H);
IR (cm~1) 3516, 3408, 3273, 3207, 2110, 1483, 1446, 1381, 1329, 1244,
1
020, 974, 916, 763, 736, 646; mp 206È207 ¡C. 6: 1H NMR d 7.85 (d, J
8
Hz, 2H), 7.46 (d, J 8 Hz, 2H), 6.22 (s, 2H), 2.65 (s, 2H), 2.60 (s, 2H);
IR (cm~1) 3342, 3312, 3283, 3273, 3146, 3050, 2957, 2114, 1635, 1487,
1
*
452, 1394, 1313, 1161, 1128, 989, 945, 763, 655; mp 134 ¡C.
* Crystal data. 2: (C H O , M \ 160.16). Orthorhombic, Pbca;
1
0 8 2
a \ 8.8316(2), b \ 5.900 30(10), c \ 15.6123(4) AŽ , U \ 813.54(3) AŽ 3,
Z \ 4, D \ 1.308
g cm~3, 934 unique reÑections, 837 with
c
F2 [ 2p(F2). Final R \ 0.036 (observed), 0.041 (all); wR(F2) \ 0.088
6
(
observed), 0.095 (all). 3: (C
H
O , M \ 260.28). Triclinic, P1;
18
12
2
a \ 8.7684(18), b \ 8.9558(18), c \ 10.315(2)
AŽ
,
a \ 113.78(3),
b \ 102.06(3), c \ 102.59(3)¡, U \ 682.2(2) A
Ž
3, Z \ 2, D \ 1.267 g
c
cm~3, 3623 unique reÑections, 2404 with F2 [ 2p(F2). Final
R \ 0.054 (observed), 0.097 (all); wR(F2) \ 0.108 (observed), 0.133
(
all). 6: (C H O , M \ 210.22). Monoclinic, P2 /c; a \ 10.8247(3),
14
10
2
1
b \ 22.6384(8), c \ 10.4783(3) AŽ , b \ 118.1850(10)¡, U \ 2263.28(12)
A
Ž
3, Z \ 8, D \ 1.234 g cm~3, 6159 unique reÑections, 3713 with
c
F2 [ 2p(F2). Final R \ 0.060 (observed), 0.108 (all); wR(F2) \ 0.140
(
observed), 0.160 (all). All data were collected on a Bruker SMART
CCD di†ractometer at 150 K using Mo-Ka radiation (j \ 0.710 73
), in the x-scan mode. Absorption correction was made by the
A
Ž
t-scans method. Structure solution and reÐnement was carried out
with SHELX-97. CCDC reference number 440/157. See http://
www.rsc.org/suppdata/nj/2000/a908233f/ for crystallographic Ðles in
.
¤
cif format.
¤ Whether structural orthogonality (e†ective insulation) also calls for
physical orthogonality is a matter for future discussion.
1
2
3
A. Nangia and G. R. Desiraju, T op. Curr. Chem., 1998, 198, 57.
G. R. Desiraju, Chem. Commun., 1997, 1475., .
(a) O. Ermer and A. Eling, J. Chem. Soc., Perkin T rans. 2, 1994,
925. (b) F. H. Allen, V. J. Hoy, J. A. K. Howard, V. R. Thalladi,
Fig. 3 (a) Crystal structure of alkynol 6. Notice the near identity to 3
in Fig. 2(a). (b) Interdigitation of naphthyl residues in the crystal struc-
ture of 6. Compare this with Fig. 2(b).
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L etter a908233f
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