Correspondence between Molecular Functionality and Crystal Structures. Supramolecular Chemistry of a Family of Homologated Aminophenols

Article abstract of DOI:10.1021/ja037227p

The crystal structures and packing features of a family of 13 aminophenols, or supraminols, are analyzed and correlated. These compounds are divided into three groups: (a) compounds 1-5 with methylene spacers of the general type HO-C₆H₄-(CH₂)n- C₆H ₄-NH₂ (n = 1 to 5) and both OH and NH₂ in a para position; (b) compounds la, 2a, 2b, 2c, and 3a in which one or more of the methylene linkers in 1 to 3 are exchanged with an S-atom; and (c) compounds 2d, 1b, and 6a prepared with considerations of crystal engineering and where the crystal structures may be anticipated on the basis of structures 1-5, 1a, 2a, 2b, 2c, and 3a. These 13 aminols can be described in terms of three major supramolecular synthons based on hydrogen bonding between OH and NH₂ groups: the tetrameric loop or square motif, the infinite N(H)O chain, and β-As sheet. These three synthons are not completely independent of each other but interrelate, with the structures tending toward the more stable β-As sheet in some cases. Compounds 1-5 show an alternation in melting points, and compounds with n = even exhibit systematically higher melting points compared to those with n = odd. The alternating melting points are reflected in, and explained by, the alternation in the crystal structures. The n = odd structures tend toward the β-As sheet as n increases and can be considered as a variable series whereas for n = even, the β-As sheet is invariably formed constituting a fixed series. Substitution of a methylene group by an isosteric S-atom may causes a change in the crystal structure. These observations are rationalized in terms of geometrical and chemical effects of the functional groups. This study shows that even for compounds with complex crystal structures the packing may be reasonably anticipated provided a sufficient number of examples are available.

Full text of DOI:10.1021/ja037227p

Published on Web 11/01/2003
Correspondence between Molecular Functionality and Crystal
Structures. Supramolecular Chemistry of a Family of
Homologated Aminophenols
Venu R. Vangala,† Balakrishna R. Bhogala,† Archan Dey,† Gautam R. Desiraju,*,†
Charlotte K. Broder,‡ Philip S. Smith,‡ Raju Mondal,‡ Judith A. K. Howard,*,‡ and
Chick C. Wilson§
Contribution from the School of Chemistry, UniVersity of Hyderabad, Hyderabad 500 046, India,
Department of Chemistry, UniVersity of Durham, South Road, Durham DH1 3LE, U.K.,
Department of Chemistry, UniVersity of Glasgow, Glasgow G12 8QQ, U.K., and
ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, Oxon OX11 0QX, U.K.
Received July 11, 2003; E-mail: desiraju@uohyd.ernet.in
Abstract: The crystal structures and packing features of a family of 13 aminophenols, or supraminols, are
analyzed and correlated. These compounds are divided into three groups: (a) compounds 1-5 with
methylene spacers of the general type HO-C6H4-(CH2)n-C6H4-NH2 (n ) 1 to 5) and both OH and NH2
in a para position; (b) compounds 1a, 2a, 2b, 2c, and 3a in which one or more of the methylene linkers in
1 to 3 are exchanged with an S-atom; and (c) compounds 2d, 1b, and 6a prepared with considerations of
crystal engineering and where the crystal structures may be anticipated on the basis of structures 1-5,
1a, 2a, 2b, 2c, and 3a. These 13 aminols can be described in terms of three major supramolecular synthons
based on hydrogen bonding between OH and NH2 groups: the tetrameric loop or square motif, the infinite
N(H)O chain, and the â-As sheet. These three synthons are not completely independent of each other but
interrelate, with the structures tending toward the more stable â-As sheet in some cases. Compounds 1-5
show an alternation in melting points, and compounds with n ) even exhibit systematically higher melting
points compared to those with n ) odd. The alternating melting points are reflected in, and explained by,
the alternation in the crystal structures. The n ) odd structures tend toward the â-As sheet as n increases
and can be considered as a variable series whereas for n ) even, the â-As sheet is invariably formed
constituting a fixed series. Substitution of a methylene group by an isosteric S-atom may causes a change
in the crystal structure. These observations are rationalized in terms of geometrical and chemical effects
of the functional groups. This study shows that even for compounds with complex crystal structures the
packing may be reasonably anticipated provided a sufficient number of examples are available.
Introduction
supramolecular behavior of a functional group in a molecule
depends also on the position and location of the other func-
A major challenge in the crystal engineering of molecular
solids1 is the absence of a direct correspondence between
molecular functionality and crystal structure. This arises from
the complementary nature of molecular recognition so that the
tionalities, with the added caveat that all portions of a molecule
including the hydrocarbon residues have supramolecular func-
tionality. Crystal structures arise therefore from a complex
convolution of recognition events.2 In an attempt to simplify
this complexity, the structural chemist identifies small struc-
tural units, known as supramolecular synthons,3 that are asso-
ciated with certain combinations of molecular functionality and
that are reproduced from structure to structure within a family
of molecules. When such synthons are identified, crystal design
can become more straightforward. Supramolecular synthons are
more representative of crystal packing features than individual
interactions, and it is often more appropriate to describe struc-
† University of Hyderabad.
‡ University of Durham.
§ Glasgow University and ISIS Facility, Rutherford Appleton Laboratory.
(1) Selected references on crystal engineering of organic molecular solids
include the following. (a) Desiraju, G. R. Crystal Engineering. The Design
of Organic Solids; Elsevier: Amsterdam, 1989. (b) The Crystal as a
Supramolecular Entity. Perspectives in Supramolecular Chemistry, Vol.
2; Desiraju, G. R., Ed.; Wiley: Chichester, 1996. (c) ComprehensiVe
Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D.
D., Vo¨gtle, F., Eds.; Pergamon: Oxford, 1996; Vols. 6, 7, 9, 10. (d). Design
of Organic Solids; Weber, E., Ed.; Topics in Current Chemistry; Springer:
Berlin, 1998; Vol. 198. (e) Crystal Engineering: From Molecules and
Crystals To Materials; Braga, D., Orpen, A. G., Eds.; NATO ASI Series
Kluwer: Dordecht, The Netherlands, 1999. (f) Crystal Engineering: The
Design and Application of Functional Solids; Seddon, K. R., Zaworotko,
M. J., Eds.; NATO ASI Series Kluwer: Dordecht, The Netherlands, 1999.
(g) Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; Wiley:
Chichester, 2000; Vol. 11, pp 389-463. (h) Desiraju, G. R. Curr. Sci. 2001,
81, 1038. (i) Sharma, C. V. K. Cryst. Growth Des. 2002, 2, 465. (j) Crystal
Design. Structure and Function; Perspectives in Supramolecular Chemistry,
Vol. 7; Desiraju, G. R., Ed.; Wiley: Chichester, 2003.
(2) That observed crystal structures cannot be predicted so easily is re-
vealed in the difficulties encountered in crystal structure prediction.
See: (a) Gavezzotti, A. Acc. Chem. Res. 1994, 27, 309. (b) Beyer, T.;
Lewis, T.; Price, S. L. CrystEngComm 2001, 3, 178. (c) Desiraju, G. R.
Nature Materials 2002, 1, 77. (d) Dunitz, J. D. Chem. Commun. 2003,
545.
(3) (a) Desiraju, G. R. Angew. Chem., Int. Ed. Engl. 1995, 34, 2311. (b) Nangia,
A.; Desiraju, G. R. Top. Curr. Chem. 1998, 198, 57.
9
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J. AM. CHEM. SOC. 2003, 125, 14495-14509
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A R T I C L E S
Vangala et al.
tural hierarchies4 in terms of synthons rather than interactions
or functional groups.
1) that contain four molecular functionalities. These are
respectively, the hydroxy group (phenolic), the amino group
(anilino), phenyl rings, and a linker group, typically a polym-
ethylene chain, which links phenyl rings. We attempt to find
the correspondence between molecular structure and crystal
structure for these compounds. We show that, in many cases,
the observed crystal structures result from a fine balance between
several factors leading to both hierarchic packing and to
structures wherein interaction interference is more pronounced.
The family of aminophenols or supraminols, molecules that
contain equal stoichiometries of hydroxyl and amino groups,
offers sufficient structural consistency with enough supramo-
lecular diversity to explore properly the interactions between
molecular functionality in crystal packing. Ermer and co-
workers5 and Hanessian and co-workers6 elaborated elegant
principles of recognition for such molecules. According to these
researchers, an -OH group with one hydrogen bond donor and
two acceptors and an -NH2 group with two hydrogen bond
donors and one acceptor constitute a mutually compatible set
of molecular functionalitysone that permits the formation of
one O-H‚‚‚N and two N-H‚‚‚O hydrogen bonds resulting in
a complete saturation of the hydrogen bonding potential of both
functional groups. In molecules such as 4-aminophenol (4AP),
these hydrogen bonds form a N(H)O sheet structure in which
the hydrogen bonds are arranged in a hexagonal manner, like
the chair form of cyclohexane (Figure 1). We use the notation
N(H)O in this paper to simultaneously refer to O-H‚‚‚N and
N-H‚‚‚O hydrogen bonds. This arrangement is topologically
equivalent to the sheet structure of â-arsenic and will be re-
ferred to as such in this paper. The â-As sheet and its variants
have been noted in a number of N(H)O structures of suprami-
nols.7 Independently, Howard, Desiraju, and co-workers8 rec-
ognized that factors other than N(H)O saturation need to be
considered even for some simple aminols. In 2- and 3-ami-
nophenol (2AP, 3AP), for example, the potential for the
formation of strong O-H‚‚‚N and N-H‚‚‚O bonds is not
completely fulfilled. Instead, there is the formation of a weak
N-H‚‚‚π hydrogen bridge9 (Figure 2). These authors rational-
ized this behavior as being driven by the need to form
herringbone interactions between phenyl residues. The change
from the 4AP structure to the 2AP and 3AP structures is
therefore a change from a more hierarchical arrangement to one
where there is more structural interference10 between molecular
functionality. In effect, even with just three functional groups,
hydroxy, amino, and phenyl, there are two quite distinct
structural possibilities.
Experimental Section
General Methods. Melting points of compounds 1-5 were mea-
sured on a Perkin-Elmer Model DSC-4 melting point apparatus. All
other melting points were recorded on a Fisher-Johns melting point
apparatus and are uncorrected. All reactions were carried out using
standard techniques and general literature procedures. The synthesis
of the aminophenols in this study are given, whenever there is a
significant variation from the literature procedures. Details of the
synthetic procedures for compounds 1-5, 1a, 2a, 2b, 2c, 3a, 2d, 1b,
and 6a are given in the Supporting Information.
X-ray and Neutron Data Collections and Crystal Structure
Determinations. Diffraction quality single crystals of all compounds
were obtained by slow evaporation from various solvents. The X-ray
data were collected on a Bruker SMART-1000 diffractometer (1-5,
2b, 2c, 3a, 1b) or the Bruker SMART-6000 diffractometer (1a, 2d,
and 6a) using Mo KR radiation. X-ray data for 2a were collected on a
Rigaku AFC6S diffractometer using Cu KR radiation. The structure
solution and refinements were carried out using SHELXTL programs.11a
The neutron structure determination of 1 was carried out at the ISIS
pulsed neutron source on the Laue time-of-flight diffractometer,
SXD,11b,c using the multicrystal method:11d a sample of 4 crystals was
mounted in the SXD ω-CCR and data collected at 12 K in a series of
10 frames with 25°ω steps. Intensities from all four crystals were
extracted, resulting in 2403 unique, merged reflections. All interatomic
distance and related calculations were carried out with PLATON2002.12
For further details see Table 1 and the Supporting Information.
Results and Discussion
A. Methylene Spacer Structures. Ermer and Eling noted5
that 4-(4-aminophenyl)phenol (4APP) forms a structure that is
directly analogous to 4AP, consisting of parallel â-As sheets
linked by a biphenyl spacer groupsthe phenyl group in 4AP is
in effect replaced by the biphenyl group in 4APP (Figures 1b
and 1c). Both molecules are in the same space group (Pna21)
with similar dimensions for the a (∼8.1 Å) and b (∼5.3 Å)
axes, and this is the plane of â-As sheets. The change in spacer
is reflected in the length of the c axis, which at 12.95 Å for
4AP, and 21.22Å for 4APP, is approximately equal to the
molecular length.
By examining these two â-As structures, the question arose
as to whether this structure type could be reproduced with more
extended linking units between the aniline and phenol moieties.
To study this question, and to establish the requirements for
â-As sheet formation in higher aminophenols, a series of
4-amino-4′-hydroxydiphenyl-n-alkanes (where n ) 1-5) were
synthesized. In effect, 4APP is the n ) 0 compound. This series
of homologated aminols also provides an opportunity for
The present paper explores these ideas further and provides
an analysis of the crystal structures of 13 supraminols (Scheme
(4) (a) Aakero¨y, C. B.; Beatty, A. M.; Helfrich, B. A. J. Am. Chem. Soc. 2002,
124, 14425. (b) Vishweshwar, P.; Nangia, A.; Lynch, V. M. Cryst. Growth
Des. 2003, 3, 783.
(5) Ermer, O.; Eling, A. J. Chem. Soc., Perkin Trans. 2 1994, 925.
(6) (a) Hanessian, S.; Gomtsyan, A.; Simard, M.; Roelens, S. J. Am. Chem.
Soc. 1994, 116, 4495. (b) Hanessian, S.; Simard, M.; Roelens, S. J. Am.
Chem. Soc. 1995, 117, 7630. (c) Hanessian, S.; Saladino, R.; Margarita,
R.; Simard, M. Chem. Eur. J. 1999, 5, 2169. (d) Hanessian, S.; Saladino,
R. In Crystal Design. Structure and Function. Perspectives in Supramo-
lecular Chemistry, Vol 7; Desiraju, G. R., Ed.; Wiley: New York; 2003,
p 77.
(7) Selected references that describe the structural chemistry of supraminols
include the following: (a) Loehlin, J. H.; Etter, M. C.; Gendreau, C.;
Cervasio, E. Chem. Mater. 1998, 6, 1218. (b) Loehlin, J. H.; Franz, K. J.;
Gist, L.; Moore, R. H. Acta Crystallogr. 1998, B54, 695. (c) Toda, F.;
Hyoda, S.; Okada, K.; Hirotsu. K. J. Chem. Soc., Chem. Commun. 1995,
1531. (d) Roelens, S.; Dapporto, P.; Paoli, P. Can. J. Chem. 2000, 78,
723. (e) Dapporto, P.; Paoli, P.; Roelens, S. J. Org. Chem. 2001, 66, 4930.
(f) Lewinski, J.; Zachara, J.; Kopec, T.; Starawiesky, B. K.; Lipkowski, J.;
Justyniak, I.; Kolodziejczyk, E. Eur. J. Inorg. Chem. 2001, 5, 1123. (g)
O’Leary, B.; Splading, T. R.; Ferguson, G.; Glidewell, C. Acta Crystallogr.
2000, B56, 273.
(11) (a) SHELXTL version 5.1. Bruker AXS: Madison, WI, 2001. (b) Wilson,
C. C. J. Mol. Struct. 1997, 405, 207. (c) Allen, F. H.; Howard, J. A. K.;
Hoy, V. J.; Desiraju, G. R.; Reddy, D. S.; Wilson, C. C. J. Am. Chem.
Soc. 1996, 118, 4081. (d) Wilson, C. C. J. Appl. Crystallogr. 1997, 30,
184.
(12) Spek, A. L. PLATON, A multipurpose Crystallographic Tool, Utrecht
University, Utrecht, The Netherlands, 2002.
(8) Allen, F. H.; Hoy, V. J.; Howard, J. A. K.; Thalladi, V. R.; Desiraju, G.
R.; Wilson, C. C.; McIntyre, G. J. J. Am. Chem. Soc. 1997, 119, 3477.
(9) Desiraju, G. R. Acc. Chem. Res. 2002, 35, 565.
(10) (a) Desiraju, G. R. Nature 2001, 412, 397. (b) Madhavi, N. N. L.; Bilton,
C.; Howard, J. A. K.; Allen, F. H.; Nangia, A.; Desiraju, G. R. New J.
Chem. 2000, 24, 1.
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Supramolecular Chemistry of Homologated Aminophenols
A R T I C L E S
Figure 1. (a) â-As sheet, (b) stereoview of the â-As sheet structure in 4-aminophenol (4AP), (c) stereoview of the â-As sheet structure in 4-(4-aminophenyl)-
phenol (4APP) (adapted from ref 5).
investigation into the even-odd effect in the alternation of
melting points and other physical properties of n-alkanes and
substituted n-alkanes.13,14 These aminols also provided an
interesting synthetic exercise, with each compound requiring a
different multistep route. Details are given in the Supporting
Information.
n-Even Structures. 4-(4-aminophenethyl)phenol, 2, forms
crystals with a structure that is directly analogous to that of
4AP and 4APP. Parallel â-As sheets are linked by the rest of
the molecule (Figure 3). The hydrogen bond distances within
(13) Baeyer, A. Ber. Chem. Ges. 1877, 10, 1286.
9
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A R T I C L E S
Vangala et al.
Figure 2. Hydrogen bridges in (a) 2-aminophenol (2AP) and (b) 3-aminophenol (3AP). The infinite chain N(H)O synthon is highlighted in both cases.
Scheme 1
by herringbone interactions with ring plane-ring plane angles
of 69° and 72°, respectively, for the phenol and anilino ring
pairs.
n-Odd Structures. Low-temperature X-ray and neutron data
were collected for 4-(4-aminobenzyl)phenol, 1, and are in good
agreement. In the following discussion, the geometries derived
from both the X-ray (X) and neutron (N) data sets are quoted.
Complementary recognition of NH2 and OH moieties to give a
saturated N(H)O packing is not observed. Instead, an unsaturated
arrangement of N(H)O hydrogen bonds is found. The structure
is based on a 4-fold arrangement of N(H)O hydrogen bonds, a
tetramer synthon, henceforth referred to as a square motif
(Figure 5). The anilino hydrogen that is not involved in a
hydrogen bond to the hydroxy group interacts with an adjacent
phenol ring to form a N-H‚‚‚π bridge16 (2.43 Å, 156° (X),
2.39 Å, 155.5° (N)). A C-H‚‚‚π interaction directed at the other
face of the same phenol ring and another C-H‚‚‚π bond with
the anilino ring completes the packing.
the sheet are O-H‚‚‚N (1.84 Å, 173.3°) and N-H‚‚‚O (2.13
Å, 169.7°; 2.30 Å, 177.3°). The structure is further stabilized
by herringbone interactions15 with an angle of 67° between
adjacent phenol rings and of 70° between adjacent anilino rings.
There are subtle differences between this â-As sheet and those
in 4AP and 4APP; first, there is a change in space group from
Pna21 to Pc; second, while 4AP and 4APP are in a wurtzite-
like structure, compound 2 is analogous to diamond.
The structure of 4-[4-(4-aminophenyl)butyl]phenol, 4, is
isostructural with that of 2 and â-As sheets are observed (Fig-
ure 4). The space group is Pc and the structure is diamond-
like rather than wurtzite-like. The structure is further stabilized
With all π-bases there is some question as to where exactly
the hydrogen bond accepting site is located. Questions of this
kind can only be answered satisfactorily with neutron diffraction
analysis. In X-H‚‚‚π hydrogen bonds the X-H bond vector
can be directed either toward the ring centroid or toward an
individual carbon-carbon bond within the ring. In the
N1-H1b‚‚‚πA interaction (interaction iv in Figure 5b), the N-H
vector is directed toward one of the C-C bonds of the phenol
ring but the C9-H9‚‚‚πA bond to the other face of the same
ring (v in Figure 5b) is directed toward the ring centroid. In
contrast, the C-H vector in the C5-H5‚‚‚πB interaction (iii in
Figure 5a) is directed toward one of the C-C bonds. In all cases,
(14) (a) Thalladi, V. R.; Nu¨sse, M.; Boese, R. J. Am. Chem. Soc. 2000, 122,
9227. (b) Thalladi, V. R.; Boese, R. New J. Chem. 2000, 24, 579. (c)
Thalladi, V. R.; Boese, R.; Weiss, H. C. J. Am. Chem. Soc. 2000, 122,
1186. (d) Thalladi, V. R.; Boese, R.; Weiss, H. C. Angew. Chem., Int. Ed.
2000, 39, 918. (e) Boese, R.; Weiss, H. C.; Bla¨ser, D. Angew. Chem., Int.
Ed. Engl. 1999, 38, 988. (f) Bond, A. D. Chem. Commun. 2003, 250.
(15) (a) Throughout this work the herringbone interaction has been described
in terms of the angle between adjacent aromatic rings. This is not the only
factor influencing the nature of this interaction, and the separation and the
degree to which the rings are offset is also important; however, the relative
ring plane angle gives a single value by which the interactions may be
conveniently compared. (b) Zorkii, P. M.; Zorkaya, O. N. J. Struct. Chem.
1995, 36, 704. (c) Gavezzotti, A. Chem. Phys. Lett. 1988, 161, 67.
(16) (a) Malone, J. F.; Murray, C. M.; Charlton, M. H.; Docherty, R.; Lavery,
A. J. J. Chem. Soc., Faraday Trans. 1997, 93, 3429. (b) Viswamitra, M.
A.; Radhakrishnan, R.; Bandekar, J.; Desiraju, G. R. J. Am. Chem. Soc.
1993, 115, 4868. (c) Ciunik, Z.; Desiraju, G. R. Chem. Commun. 2001,
703. (d) Hanton, L. R.; Hunter, C. A.; Purvis, D. H. J. Chem. Soc., Chem.
Commun. 1992, 1134. (e) Bond, A. D. Chem Commun. 2002, 1664. (f)
Nishio, M.; Hirota, M.; Umezawa, Y. The CH/π Interaction; Wiley-VCH:
New York, 1998.
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Supramolecular Chemistry of Homologated Aminophenols
A R T I C L E S
Table 1. Crystallographic Data and Structure Refinement Parameters for the Compounds in This Study
1N
1X
2
3
4
5
emp. form.
form. wt.
crystal system
space group
T [K]
a [Å]
b [Å]
C13H13NO
199.25
monoclinic
P21/n
C14H15NO
213.27
orthorhombic
Pc
100(2)
13.682(3)
5.2619(11)
8.1916(2)
90
107.28(3)
90
2
563.1(2)
1.258
C15H17NO
227.30
monoclinic
Pca21
100(2)
23.9370(7)
6.2160(2)
8.3970(3)
90
C16H19NO
241.32
monoclinic
Pc
105(2)
15.7888(16)
5.2088(6)
8.3399(8)
90
100.912(5)
90
2
673.48(12)
1.190
C17H21NO
255.35
monoclinic
Pc
12(2)
100(2)
100(2)
5.9180(12)
19.213(4)
9.6510(19)
90
5.9820(3)
19.3670(9)
9.7390(4)
90
14.9554(9)
11.2370(8)
8.6841(6)
90
90.893(3)
90
c [Å]
R [deg]
â [deg]
γ [deg]
Z
101.25(3)
90
100.860(2)
90
90
90
4
4
4
V [Å3]
1076.3(4)
1.230
1108.09(9)
1.194
1249.41(7)
1.208
1459.2(2)
1.162
D
calc [mg/m3]
R1 [I > 2σ(I)]
0.0791
0.2230
1.081
0.0449
0.1049
1.030
0.0405
0.1087
1.034
0.0389
0.0856
1.016
0.0418
0.0921
1.030
0.0355
0.0885
1.033
wR2
GOF
structure
square motif
147.59
â-As
infinite chain
141.96
124
â-As
infinite chain
106.56
129 (A)
125 (B)
25 and 20
0.67
mp [°C]
222.46
174
185.97
174
C-O, C-N angle [deg]a
117
herringbone angle [deg]b
Ck* [%]c
88
67 and 70
0.71
0.320
41
0.68
0.284
69 and 72
0.69
0.304
0.69
0.305
0.66
pyramidal factord
0.278
A ) 0.308
B ) 0.347
lattice energies
[kcal/mol]e:
van der Waals
electrostatic
hydrogen bond
total energy
-15.5103
-12.6148
-5.8331
-16.9782
-10.5619
-6.4404
-22.6960
-14.9624
-9.0674
-23.9593
-13.3021
-5.2543
-25.8799
-15.2413
-8.8910
-26.5133
-12.8726
-6.2596
-33.9582
-33.9805
-46.7258
-42.5157
-50.0122
-45.6455
1a
2a
2b
2c
3a
2d
1b
6a
emp. form.
form. wt.
crystal system
space group
T [K]
a [Å]
b [Å]
C12H11NOS
217.28
monoclinic
P21/n
C13H13NOS
231.30
monoclinic
Pc
100(2)
13.844(3)
5.1626(10)
8.2485(16)
90
107.22(3)
90
2
563.07(21)
1.364
C13H13NOS
231.30
monoclinic
Pc
120(2)
13.7422(12)
5.1725(4)
8.3055(7)
90
105.548(4)
90
2
568.76(8)
1.351
C12H11NOS2
249.34
monoclinic
P21/c
C14H15NOS
C14H13NO
211.25
monoclinic
Pc
120(2)
12.951(8)
5.226(3)
8.046(3)
90
98.12(3)
90
2
539.2(5)
1.301
C12H11NO2
201.22
monoclinic
Cc
120(2)
22.491(1)
5.4647(2)
8.0466(4)
90
95.674(2)
90
4
984.14(8)
1.358
C12H11NO
185.22
orthorhombic
Pca21
120(2)
19.2352(8)
6.0039(3)
8.1627(4)
90
90
90
4
942.68(8)
1.305
245.33
monoclinic
Pc
100(2)
12.6341(9)
5.8636(4)
8.5671(5)
90
90.351(3)
90
2
634.65(7)
1.284
120(2)
100(2)
9.8597(3)
10.0879(3)
21.8081(7)
90
102.809(1)
90
10.4321(12)
8.1179(11)
14.791(2)
90
109.633(6)
90
c [Å]
R [deg]
â [deg]
γ [deg]
Z
8
4
V [Å3]
2115.13(11)
1.365
1179.8(3)
1.404
D
calc [mg/m3]
R1 [I > 2σ(I)]
0.0464
0.1242
1.034
0.0435
0.1170
1.095
0.0402
0.0841
1.021
0.0348
0.0836
1.078
0.0322
0.0822
1.055
0.0392
0.0996
1.045
0.0329
0.0863
1.047
0.0378
0.0930
1.033
wR2
GOF
structure
mp [°C]
square motif
147-148
106.93 (A)
100.16 (B)
75 (A) 71 (B)
â-As
â-As
infinite chain
113-115
91.184
infinite chain
116-118
115.6
â-As
â-As
infinite chain
180-182
121.4
211-212
171.9
205-207
174.7
272-275
173.8
155-157
141.6
C-O, C-N angle
[deg]a
herringbone
angle [deg]b
Ck* [%]c
68 and 71
69 and 72
86
74 and 49
67 and 70
62 and 69
89.4
0.70
0.262 (A)
0.315 (B)
0.713
0.328
0.706
0.300
0.69
0.290
0.685
0.318
0.723
0.300
0.716
0.337
0.703
0.300
pyramidal factord
lattice energies
[kcal/mol]e:
van der Waals
electrostatic
hydrogen bond
total energy
-21.2104
-13.4020
-5.4285
-22.8127
-18.4422
-8.4105
-24.1992
-18.9782
-8.8847
-23.6826
-14.8522
-7.4514
-24.0041
-12.7148
-5.9412
-23.5826
-16.0236
-8.2482
-18.7798
-16.7818
-7.4019
-16.5686
-14.2359
-6.7081
-40.0409
-49.6654
-52.0621
-45.9862
-42.6601
-47.8544
-42.9635
-37.5126
a The angles between the C-O and C-N vectors in the compounds have been calculated using RPluto. This gives a measure of the linearity of the
molecule. b The angles between two adjacent aromatic ring planes have been calculated using RPluto (phenol-phenol rings and anilino-anilino rings (2
values) or phenol-anilino rings (one value) depending on the relative orientation of the adjacent molecules head to head or head to tail. c Ck*, packing
e
coefficient calculated with PLATON. d The perpendicular distance from the basal plane to the apex of the pyramid. Lattice energies calculated using Cerius2
from Accelrys.
the direction of the X-H vector with the closest approach is to
the ring centroid and not to a specific C-C bond. Using the
X-H‚‚‚π categories defined by Malone et al.,16a N1-H1b‚‚‚πA
and C9-H9‚‚‚πA are type I whereas C5-H5‚‚‚πB is a type III
interaction. Full details of the geometries are given in the
Supporting Information.
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A R T I C L E S
Vangala et al.
the former (B ) N(21)O(21)C(21-35)) is unsaturated (forming only
two hydrogen bonds at each O and N-atom and requiring
N-H‚‚‚π and C-H‚‚‚O bonds to complete the supramolecular
valence).
The structures of aminols 5 and 3 appear to be very similar;
in both cases the major structural synthon is the infinite chain
of N(H)O hydrogen bonds (compare Figures 6 and 7b).
However, in 5 the infinite chains are partially cross-linked by
additional N(H)O interactions so that they can be considered
as running in two directions (Figure 8). For comparison, â-As
sheets can be considered as fully cross-linked infinite chains.
Therefore, 5 can be considered as bridging the â-As sheet
(aminols 2 and 4) and infinite chain structures (aminol 3), with
molecules A and B in the â-As structure and the (single) infinite
chain structure, respectively. As in 3 there is no evidence of
stabilization by herringbone interactions; the ring plane (A)-
ring plane (B) angle between adjacent molecules is 25° and 20°.
One could say that 5 has the same basic structure type as 3, but
strives toward the â-As sheet structure.
Figure 3. Stereoview of the â-As sheet in 4-(4-aminophenethyl)-
phenol, 2.
General Discussion of n-Even and n-Odd Structures. This
is a very interesting series and unusual in both the extent of the
structural repetition and the degree to which the structural
changes within the series can be understood and explained. The
structures observed can be described by just three major
synthons: the square motif, the infinite chain, and the â-As
sheet. The best way to understand the relationship between these
five structures is in terms of the infinite chain of N(H)O
hydrogen bonds. The â-As sheet {4APP (or 0), 2, and 4} can
be considered as a very special case of the infinite chain wherein
the chains run in two directions. In 3 only single or one-
dimensional chains are found. In 5, each symmetry-independent
molecule has one of the above characteristics. The underlying
reason for using the infinite chain as the basic structure motif
can be seen from the unit cell dimensions: In all the cases where
there is an infinite chain (2 through 5), the chain runs parallel
to the c axis and the dimensions of the c axis are approximately
equal (8.2-8.7 Å). In the â-As sheet structures, the b axis (in
the plane of the â-As sheet) is also equal, and the a axis reflects
the overall length of the molecule.
From this series it would appear that the driving force for
the formation of â-As structures, over the (single) infinite chains,
is the molecular geometry. While 4AP, 4APP, 2, and 4 are
approximately linear, 2AP, 3AP, 1, 3, and 5 are much more
bent. A measure of molecular linearity can be obtained from
the angle between the C-O and the C-N vectors (see Table
1). This angle is nearly 180° for the â-As structures and close
to 120° for the other structures. The structures with n ) odd
can be considered as tending toward the â-As structure as the
value of n increases: 1 has a structure that is far from the â-As
structure, without any infinite chains, just square motifs. 3 is
closer, with infinite chains, while 5 is still closer to the â-As
structure with cross-linked infinite chains. The fact that 5 has
two molecules in the asymmetric unit suggests that the structure
is tending toward the â-As structure, preferring to assume a
more intricate structure, involving two symmetry-independent
molecules, that is more closely related to the â-As sheet rather
than a simpler structure such as 3.17 An overlay of the sheets
Figure 4. Stereoview of the â-As sheet in 4-[4-(4-aminophenyl) butyl]-
phenol, 4.
The most notable supramolecular synthon in 4-[3-(4-ami-
nophenyl)propyl]phenol, 3, is a chain of N(H)O hydrogen bonds.
This motif (previously observed in 2AP and 3AP) is of major
significance in this structural series and is henceforth referred
to as the infinite chain. The moieties at both ends of a given
molecule are involved in different chains, so that the molecule
acts as a linker between chains, thus creating sheets. Once again,
the amino hydrogen atom that is not involved in the chain forms
an N-H‚‚‚π hydrogen bridge (2.38 Å, 161.2°). This structure
is directly comparable to 3AP (Figure 6), but not to 2AP.8 Both
3 and 3AP are in the same space group Pca21 and the axial
lengths along b and c are nearly equal.
There are two independent molecules in the asymmetric unit
of 4-[5-(4-aminophenyl)pentyl]phenol, 5, and these molecules
have different geometries (Figure 7a). One is similar to 3 while
the other is more twisted. The latter (A ) N(1)O(1)C(1-15)) is
saturated in terms of N(H)O hydrogen bonds (forming 3
N(H)O hydrogen bonds at each oxygen and nitrogen), while
(17) A very similar series that shows this sort of structural modulation is the
2,3-dicyano-5,6-dichloro-1,4-dialkoxybenzenes studied by Reddy, D. S.;
Ovchinnikov, Y. E.; Shishkin, O. V.; Struchkov, Y. T.; Desiraju, G. R. J.
Am. Chem. Soc. 1996, 118, 4085.
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Supramolecular Chemistry of Homologated Aminophenols
A R T I C L E S
Figure 5. (a) Square motif synthon formed by O-H‚‚‚N, (i) N-H‚‚‚O (ii) hydrogen bonds and C5-H5‚‚‚πB (iii) interactions in the crystal structure of
aminol 1. (b) Notice N1-H1b‚‚‚πa (iv) and C9-H9‚‚‚πa (v) interactions to the same phenyl ring.
of the N(H)O interactions in 5 on the â-As sheet shows just
how closely these two structures are related (Figure 8).
In summary, the n ) odd series can be considered as a
variable series, with the structure moving toward a â-As sheet
structure as the length of the linker unit increases:
of the melting points but also from the marked alternation of
the crystal structure types. The even structures take the â-As
sheet structures, while the odd ones take infinite chain structures
(or a square motif structure in 1). This sort of structural modu-
lation where the types of interactions and indeed the entire
packing arrangements alternate, based on whether the member
is even or odd, is very dramatic. Lattice energy calculations18
confirm that the â-As structures are more stable. The decrease
of melting points with an increase in chain length hint also at
the importance of entropic factors (Figure 9).
1 f 3 f 5 f f â-As
In comparison, the n ) even series is a fixed series:
0 ) 2 ) 4 ) â-As
This series shows good trends that can be clearly explained
in terms of odd and even structures. However, it is still a series
that consists of only five structures. To confirm the trends
observed, structural analyses of more compounds are desirable.
This is especially true at the lower end of the n ) odd
compounds where the square motif of 1 becomes the infinite
chain motif in 3. With this aim, a selection of S-substituted
4-amino-4′-hydroxybiphenyl-n-alkanes was synthesized. The
This series also provides a good example of the even-odd
effect in substituted n-alkanes. This effect was first studied by
Baeyer in 1877, who noted that n-alkane dicarboxylic acids
where n ) even melt at higher temperatures than those where
n ) odd.13 This phenomenon has since been observed in many
other n-alkanes and end-substituted n-alkanes. In particular,
detailed studies have been carried out by Boese and co-
workers.14 The phenomenon of alternation in solid-state proper-
ties has been attributed to crystal packing factors so that even
n-alkanes pack more efficiently than odd n-alkanes. In our series,
not only is the even-odd effect apparent from the alternation
(18) Energy calculations were carried out on Indigo Solid Impact and Octane
workstations from Silicon Graphics using the Dreiding 2.21 force field in
the Cerius2 program. Cerius2, Accelrys Ltd., 334 Cambridge Science Park,
Cambridge CB4 0WN, U.K. www.accelrys.com.
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A R T I C L E S
Vangala et al.
Figure 6. Infinite chain synthon in 4-[3-(4-aminophenyl)propyl]phenol,
3. Note the similarity with the packing of 3AP shown in Figure 2.
method of exchanging one functional group with another of
similar dimensions is a technique that has greatly furthered the
field of crystal engineering. Whether the new structure is
geometrically isostructural with the original or not can reveal a
great deal about the ability and role of the exchanged group in
determining the crystal structure.
B. Sulfur Spacer Structures. Kitaigorodskii19 proposed that
under appropriate circumstances interchanging a single func-
tional group with another of comparable volume in a mole-
cule, such as the S-atom and the -CH2- group, benzene-
thiophene exchange,20 or chloro-methyl exchange,21 need not
alter the crystal structure. A CSD search22 was carried out for
Ar-S-Ar/Ar-CH2-Ar sets of compounds. A total of 21 pairs
were found of which 8 are isostructural. The S-atom is
approximately the same size as the CH2 group (22.8 Å3 and
19.1 Å3, respectively), and the idealized C-S-C angle is 100°
(19) (a) Kitaigorodskii, A. I. Molecular Crystals and Molecules; Academic: New
York, 1973. (b) Kitaigorodskii, A. I. Mixed Crystals; Springer: New York,
1984.
(20) Thallapally, P. K.; Chakraborty, K.; Carrell, H. L.; Kotha, S.; Desiraju, G.
R. Tetrahedron 2000, 56, 6721.
(21) (a) Ka´lma´n, A.; Arga´y, Fa´bia´n, L.; Bernath, G.; Fulop, F. Acta Crystallogr.
2001, B57, 539. (b) Muthuraman, M.; Le Fur, Y..; Beucher, M. B.; Masse,
R.; Nicoud, J.-F.; George, S.; Nangia, A.; Desiraju, G. R. J. Solid State
Chem. 2000, 152, 221.
(22) A search of the CSD (Version 5.23, April 2002) for error free Ar-S-Ar
organic acyclic, nonionic, no polymeric with R < 0.10. Disordered, no
coordinates present structures were excluded from the search. Of the 589
entries in the subset, 21 hits with corresponding Ar-CH2-Ar were found
of which eight are isostructural. Allen, F. H.; Kennard, O. Chem. Des.
Automat. News 1993, 8, 31.
Figure 7. (a) Space-filling model of 5 showing the two symmetry-
independent molecules. (b) Infinite chain in 4-[4-(4-aminophenyl)pentyl]-
phenol, 5. Compare this with Figure 6.
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Supramolecular Chemistry of Homologated Aminophenols
A R T I C L E S
Figure 8. Showing how the cross-linked infinite chains in supraminol 5 relate to the â-As sheet in 4 (overlaid in orange). Symmetry-independent molecules
A (green) and B (magenta) are color coded.
fide), 2b (4-amino-4′-hydroxydiphenylsulfide methane), 2c (4-
amino-4′-hydroxydiphenyldisulfide), and 3a (4-amino-4′-hy-
droxydiphenylethylsulfide). It is noteworthy that all these com-
pounds required a synthetic route for the preparation different
from that used to obtain the parent compound. Details of the
synthetic procedures are given in the Supporting Information.
Isostructural S-Spacer Supraminols. The substitution of one
CH2 group for an S-atom in compound 2 to give 2a and 2b has
very little effect on the crystal structure (Figure 10).24,25The
structure of 3a is again very similar to that of 3 and the key
synthon is the infinite chain. In 3 the molecules align head to
tail. This allows the chains to be linked into sheets, with the
molecule acting as a linker between adjacent N(H)O chains. In
3a the molecules align head to head, preventing the formation
of individual sheets (Figure 11).
Non-isostructural S-Spacer Supraminols. There are two
independent molecules in the asymmetric unit of compound
1a (molecule A ) N(1)O(1)S(1)C(1-12) and molecule B )
N(2)O(2)S(2)C(21-22)) but the geometries of both molecules, and
the way in which they interact within the crystal, are similar.
The crystal structure consists of alternate sheets of A and B
molecules. Both sheets are built up of square motifs of N(H)O
hydrogen bonds. The difference between this structure and that
of aminol 1 is that the four molecules spiral out from the square
motif, in a windmill type arrangement (Figure 12). The reason
for this difference appears to be the exchange of an N-H‚‚‚π
bond by an N-H‚‚‚S bond.26 Sheets of molecules A and B stack
alternately, with herringbone interactions between the layers
Figure 9. (a) Even-odd effect in aminols 1-5 of melting points and lattice
(23) A search of the CSD (Version 5.23, April 2002) was done for error free
energy.18 (b) Alternation in density and packing fraction.
Ar-S-S-Ar organic, aromatic, acyclic, nonionic, nonpolymeric structures
with R < 0.10. Disordered structures and those without coordinates were
compared to a C-C-C angle of 109°. However, the geometry
excluded. Fiftyone hits with torsion angles of nearly 90° were found.
(24) (a) Fa´bia´n, L.; Ka´lma´n, A. Acta Crystallogr. 1999, B55, 1099. (b) Lowdin,
of Ar-S-S-Ar (torsion angle ∼90°, see Supporting Informa-
P.-O. J. Chem. Phys. 1950, 18, 365.
tion) is very different than that of Ar-C-C-Ar or Ar-S-
(25) The near identity of the packing of 2, 2a, and 2b molecules was also
quantified with NIPMAT and simulated powder X-ray plots. For a
C-Ar (torsion angle ∼0°). Disulfide compounds are compara-
description of the NIPMAT procedure, see Supporting Information.
tively rare, with only a total of 51 CSD occurrences.23
(26) (a) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond in Structural
Chemistry and Biology; Oxford University Press: Oxford, 1999. (b)
Accordingly, we studied compounds 1a (4-amino-4′-hydroxy-
diphenylsulfide), 2a (4-amino-4′-hydroxydiphenylmethylsul-
Vangala, V. R.; Desiraju, G. R.; Jetti, R. K. R.; Bla¨ser, D.; Boese, R. Acta
Crystallogr. 2002, C58, 635.
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A R T I C L E S
Vangala et al.
Figure 10. (a) Stereoview of the â-As sheet in 4-(4-aminobenzyl sulfamyl)phenol, 2a, and (b) in 4-(4-aminophenylsulfamylmethyl)phenol, 2b.
torsion around C-C-C-C or C-S-C-C in 2, 2a, and 2b.
So 2c is U-shaped while 2, 2a, and 2b are linear. As in aminol
1, 2c can be considered in terms of dimers (Figures 13a and
5a); alternatively it can be considered in terms of the infinite
chain. In effect, 2c contains elements of both the square motif
of 1 and the infinite chain of 3 and as such may be considered
as bridging these two structural types.
General Discussion of S-Spacer Structures. Three examples
of the infinite chain motif have now been observed, 3AP, 3,
and 3a, as well as the partially cross-linked infinite chains of 5
and the fully cross-linked chains of the â-As sheet structures.
The differences between these structures may be rationalized
by analyzing the geometries and relative positions of the N(H)O
infinite chains. In the following discussion a 2D schematic
(Figure 14) of the infinite chains of N(H)O hydrogen bonds is
drawn from two different perspectives: from side on (the in-
finite chain projected on to the ac plane of the crystal lattice)
and from above (projected on to the bc plane). When con-
sidered in projection from either direction, the infinite chain
takes the form of a zigzag chain of N(H)O bonds. The zigzag
of the chain in 3 has twice the repeat unit of 3a and 5, with
peaks and troughs of the zigzag occurring only at the O-atom,
rather than peaks at O and troughs at N as in 3a and 5. This
affects the relative orientation of the N-H‚‚‚π hydrogen bonds.
In 3, they form on both sides of the chain, whereas in 3a and
5, they form only on one side. In the bc plane the situation is
different. The repeat unit of the 3a zigzag is now twice that of
3. In both 3 and 3a, the zigzag runs parallel with a peak
coinciding with a peak of the chain below. In the â-As sheet,
one zigzag chain is offset with relation to the next, allowing a
Figure 11. Infinite chain in 4-[2-(4-aminophenylsulfamyl)ethyl]phenol, 3a.
close approach between the O- and N-atoms of adjacent layers
Note the head-to-head arrangement of the molecules within a row. This
and also to the formation of additional cross-linking hydrogen
differs from the head-to-tail arrangement in aminol 3 (Figure 6).
bonds.
(ring plane angle 75°), while C-H‚‚‚O and C-H‚‚‚π interac-
tions also help to hold the sheets together.
Aminol 2c adopts a very different crystal packing than that
of 2, 2a, and 2b. This could be expected, given the pronounced
change in molecular geometry caused by the smaller torsion
angle about C-S-S-C {83.3(1)°}23, compared with the 0°
The analysis of aminol 5 is complicated by the presence of
two molecules in the asymmetric unit. In the bc plane two
different infinite chains, running in the c direction, can be
distinguished. Each chain is formed with both A and B mole-
cules. One of the chains (on average consisting of weaker
hydrogen bonds) is analogous to the infinite chain seen in 3a,
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Supramolecular Chemistry of Homologated Aminophenols
A R T I C L E S
Figure 12. Square motif in 4-(4-aminophenylsulfamyl)phenol, 1a. A sheet consisting of molecule type A is shown. B molecules form similar sheets, and
sheets of type A and type B molecules stack, alternately. Note the windmill type arrangement.
Figure 13. Crystal structure of 4-(4-aminophenyldisulfamyl)phenol, 2c (a) ac plane. Compare this with Figure 5a. (b) ab plane showing helical infinite
chain of hydrogen bonds.
while the other has a saw-tooth geometry and can be almost be
directly mapped onto a section of the â-As sheet (Figure 8).
The length of the b axis is directly related to the distance
between adjacent chains. The closest approach between two
adjacent chains occurs in the â-As sheet where the adjacent
chains are cross-linked by additional hydrogen bonds, creating
a saturated system. The distance between two adjacent chains
of the â-As sheet is approximately 5.2 Å. In 3 the separation
between chains is greater at 6.2 Å. In 3a the separation is closer
to that seen in the â-As sheet, at 5.8 Å, while in 5 there is
some cross linking between chains with the average separation
being 5.6 Å. With two molecule in the asymmetric unit, the
length of axis b is double the average separation (2 × 5.6 )
11.2).
motif structure of 1 and the infinite chain structure of 3 can be
understood by the study of aminol 2c. All the compounds studied
in this section can be included in either the variable or fixed
series already identified. 2c is considered as a bridging structure
between 1 and 3, and as such lies between them in the series.
In the same way, 3a lies between 3 and 5.
1 f 2c f 3 f 3a f 5 f f â-As: variable series
0 ) 2 ) 2a ) 2b ) 4 ) â-As: fixed series
Second, the differences between the infinite chain structures
and the â-As sheets are demonstrated, as are the relationships
between the unit cell dimensions and the structural synthons
formed. Overall, good isostructurality25 is observed between 2
and its S-analogues, while 3a is similar to 5. There is an inter-
play of geometrical and chemical effects. In 1 and 1a, where
Two significant points emerge from the study of these sulfur-
substituted compounds. First, the relationship between the square
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A R T I C L E S
Vangala et al.
Figure 14. Schematic of the N(H)O infinite chains, showing the similarities and differences of chains in 3, 3a, and 5. The â-As sheet is shown for comparison.
isostructurality is not observed, it is chemical effects that cause
the change in structure, with the N-H‚‚‚π interaction being
replaced by an N-H‚‚‚S. Similarly, the differences between 2
and 2c can be attributed to the change in torsion angle resulting
from the exchange of a CH2-CH2 for a S-S group. In the other
isostructural cases, the geometrical factors are either consistent
with or outweigh the chemical effects.
C. Design Strategies for Crystal Engineering. Crystals are
composed of molecules but crystal structures cannot be easily
derived or anticipated from molecular structures. Similar
molecules can have dissimilar crystal structures and dissimilar
molecules can have similar crystal structures. This is because
the core constituents of a crystal, the synthons, result from
complementary approaches of molecular functional groups. So,
the exact pattern formed depends not only on the functional
groups present in the molecules but also on their relative
juxtapositioning. Successful strategies of crystal engineering are
based on the supramolecular synthon approach, which simplifies
the complex problem of structure prediction into the simpler
problem of network architecture.
The patterns and trends observed so far provide a good
understanding of the structural motifs possible for aminols and
the geometrical and chemical reasons why one structural synthon
is preferred over another. In this section three compounds have
been synthesized that are related to, but intrinsically different
from, those seen previously. Each compound explores a different
aspect of the structural principles discussed above. These
structures offer a chance for crystal engineering and, where the
design strategy fails, provide further insight into the structural
chemistry of these compounds.
(i) Effect of Molecular Shape To Give the â-As Sheet.
4-[(E)-2-(4-aminophenyl)-1-ethenyl]phenol, 2d, and 2 are very
similar and the saturated ethane bond of the linker is exchanged
for an unsaturated ethene bond. This is but a small chemical
change in supramolecular terms and it is not expected that the
structure would deviate from the â-As sheet. Indeed, this was
Figure 15. â-As sheet in 4-[(E)-2-(4-aminophenyl)-1-ethenyl]phenol, 2d.
found to be the case. Equivalent synthons lead to virtually
identical crystal structures. The unit cell dimensions of 2d are
comparable to those of compounds 2, 2a, 2b, and 4,25 with the
isostructurality parameter (Π) for 2 compared with 2d of 0.027
(Figure 15).
(ii) Substitution: Shape versus Electronic Factors. 4-(4-
aminophenoxy)phenol, 1b, is the O-analogue of 1 and 1a, and
as such it might be expected to form a square motif structure.
However, while an S-atom can often be exchanged for a CH2
group to form an isostructural crystal, the same cannot be said
for exchange by oxygen.27 When the structure of 1b was
determined, it was immediately apparent from the unit cell
dimensions that the structural motif was neither that of a square
motif nor that of an infinite chain, but the â-As sheet structure
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Supramolecular Chemistry of Homologated Aminophenols
A R T I C L E S
Figure 16. â-As sheet structure of 4-(4-aminophenoxy)phenol, 1b.
Figure 18. The Infinite chain motif in 4-(3-aminophenyl)phenol, 6a.
Figure 17. The flexing of 1b to achieve a large C-O, C-N vector angle.
Note that phenolic end of the molecule is also bent to a similar degree.
2.3 Å and 2.4 Å, compared with an average value of 2.2 Å and
2.3 Å for the other â-As sheet structures.
(Figure 16)! A closer study revealed why such an unlikely result
was possible.
Finally, the greater electronegativity of the O-atom relative
to -S- and -CH2- increases the donor ability of the adjacent
phenyl hydrogen atoms (for Mulliken charges, see Supporting
Information). This promotes the formation of bifurcated
C-H‚‚‚O hydrogen bonds. This is an additional factor in pulling
adjacent molecules close together, and rather than being a
consequence of the structure, it is more likely to be playing an
important role in aligning the molecules so as to achieve the
â-As structure (Figure 16). This illustrates the role of chemical
influences. For example, if molecules of 1 were aligned in the
same way, there would be repulsion between the methylene H-
and aromatic H-atoms.
When chemical factors within the odd series are considered,
the structures can be seen to tend toward the â-As sheet as
the electronegativity increases. By replacement of -CH2- by
an S-atom, i.e., a slight increase in electronegativity, the struc-
ture of compound 1a is a square motif with additional
C-H‚‚‚S hydrogen bonds that change the motif to a windmill
arrangement. This might suggest that aminol 1b (with a greater
increase in electronegativity) could be found as either a struc-
ture similar to 1a or an infinite chain type structure. But
interestingly, 1b exceeded our predictions in achieving the target
structure, i.e., a â-As sheet structure even within the n )
odd series. It is a matter of speculation whether extensions of
the series 1 to 5 with n ) 7, 9 would adopt the â-As sheet
structure.
First, the geometry of the molecule shows that it has had to
distort to obtain as large a C-O, C-N vector angle as possible;
while the angle at the oxygen atom (C-O-C) is 120° as
expected (for CSD search see Supporting Information), the
C-O, C-N vector angle is 141° (Table 1), which is much larger
than the corresponding angle seen in any of the infinite chains
or square motif structures. To achieve this large C-O, C-N
vector angle, the whole molecule is considerably bent (Figure
17). The O-atom is shifted about 0.2 Å out of the plane of each
of the phenyl rings. The NH2 and OH groups are also bent out
of the plane of their respective phenyl rings but to a lesser extent
(0.1 and 0.06 Å, respectively).
Second, the volume of the O-atom is much less than that of
the -CH2- group or the S-atom (11 Å3 compared to 19.1 Å3
and 22.8 Å3, respectively) and this allows the molecules to fit
closer together. Further, while the molecules can pack better
than would be possible for the S or CH2 substituted structures,
they cannot pack as closely as the more linear molecules that
form â-As sheet structures. This gives rise to an elongation of
the two N-H‚‚‚O hydrogen bonds (and therefore the b axis) to
(27) The CSD (Version 5.23, April 2002) was searched for error free C-O-C
organic acyclic, aromatic, nonionic, nonpolymeric structures with R <
0.075. Disordered structures and those without coordinates were excluded.
Of the 418 entries in the subset, four hits with the corresponding C-C-C
compounds in the CSD were found of which one set is isostructural
(CAKGOK, GUHKUP).
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A R T I C L E S
Vangala et al.
Scheme 2. â-As Sheet, Infinite Chain, and Square Motif Synthonsa
a NsO represents the N(H)O hydrogen bond, i.e., either an O-H‚‚‚N or an N-H‚‚‚O hydrogen bond. Thick lines represent the hydrocarbon fragment of
the molecule.
(iii) Effect of Molecular Shape To Give the Infinite Chain.
Kitaigorodskii’s close-packing principle19 states that mutual
recognition between molecular shapes is the key element in
understanding the packing of molecular crystals. Given that 4-(3-
aminophenyl)phenol, 6a, has nearly the same shape as 3,
especially with respect to the all-important -OH and -NH2
groups, we predicted that its crystal structure would contain the
infinite chain motif. This prediction was borne out in practice.
Aminol 6a has a molecular geometry comparable with that of
3AP and 3. The angle between the C-O and C-N vectors is
121° compared to 121° for 3AP and 124° for 3. The value of
Π for 6a in relation to 3 is 0.15. The crystal packing motif is
identical, and it is only the molecular length that varies. This is
reflected in the change in length of a axis (Figure 18 cf. Figure
6). The N-H‚‚‚π bond is slightly weaker than that seen for 3
(2.51 Å, 143.7°).
We feel that a good level of understanding has now been
obtained for these supraminol systems. The infinite chain is the
key synthon in this family. The way in which the fixed and the
variable series relate to each other is also clearly understood:
It is noteworthy that the synthons discussed here are all
constructed from a combination of O-H‚‚‚N and N-H‚‚‚O
hydrogen bonds and that nowhere in these structures do
O-H‚‚‚O or N-H‚‚‚N hydrogen bonds occur.
From this work a number of further avenues of exploration
present themselves: (1) It would be interesting to extend the
4-amino-4′-hydroxybiphenyl-n-alkanes series to include the
hexane and heptane derivatives (n ) 6 and 7). The n ) 6
compound would surely take the â-As structure, since it is the
next compound in the fixed series. However, is the n ) 7
compound flexible enough to obtain the â-As sheet structure,
or will it form another bridging structure such as compound 5?
(2) A study of the 4-amino-3-hydroxy analogues of 6a would
be interesting. Would these compounds crystallize with the
infinite chain motif? (3) The structure of 1b raises the question
of the effect of steric influences on the crystal structure obtained.
Could a â-As sheet be disrupted by a sterically bulky group? If
so, what structure would then be obtained? (4) In general it
should be mentioned that polymorphism is a rare phenomenon
in aminophenols. Why is this the case, and could polymorphism
eventually be found in this family of structures? (5) In all the
supraminols discussed in this paper, the N atoms of the anilino
functionality are distinctly pyramidal (Table 1). Is this the
driving force for the formation of both â-As sheet and N-H‚
Conclusions
Scheme 2 summarizes the structural features in this family
of compounds. A partial success has been achieved in the
prediction of structural motifs of these aminols. The structures
of two of the three compounds studied with crystal engineering
considerations in mind (2d, 6a) could be anticipated reasonably
well. That the structure of 1b could not be predicted is not
particularly disappointing, and the observed structure actually
provides more useful information. Aminol 1b illustrates the
geometric limits to which the â-As sheet structure can be pushed
and a stable structure still obtained and demonstrates that
molecular linearity is not a prerequisite for â-As sheet adoption.
The lattice energy calculations (Table 1) indicate that 1b is
slightly less stable that the other â-As sheet structures but more
stable than the square motif structures.
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14508 J. AM. CHEM. SOC. VOL. 125, NO. 47, 2003

Supramolecular Chemistry of Homologated Aminophenols
A R T I C L E S
‚‚π containing structure types? (6) With the correspondence
between molecular and crystal structure now being understood
for this group of compounds, we conclude that aminophenols
are amenable to the principles of crystal engineering.
These issues are presently being studied.
Dr. V. M. Lynch (University of Texas, Austin) for data col-
lection of compound 1.
Supporting Information Available: Synthetic procedures,
hydrogen bond geometries, additional structural details, ad-
ditional figures, NIPMAT plots, simulated powder spectra, tables
of crystal data, structure solution and refinement, atomic coor-
dinates, bond lengths and angles, and anisotropic parameters
for 1 (X and N), 2-5, 1a, 2a, 2b, 2c, 3a, 1b, 2d, and 6a (PDF).
This material is available free of charge via the Internet at
http://www.pubs.acs.org.
Acknowledgment. V.R.V. and A.D. thank the CSIR for a
fellowship. B.R.B. thanks the UGC for a fellowship. C.K.B.
and P.S.S. thank EPSRC for funding. R.M. and C.K.B. thank
CCDC and Durham University for funding. G.R.D. thanks the
CSIR and DST for support of his research programs. J.A.K.H.
thanks the EPSRC for a Senior Research Fellowship. We thank
JA037227P
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