Hydrogen bonding in glyoxylamides

Article abstract of DOI:10.1080/15421400590958205

A range of secondary 2-amidophenylglyoxylamides self-assemble by intermolecular hydrogen bonding between the secondary amide proton and the 2-amidophenyl carbonyl oxygen atom.

Full text of DOI:10.1080/15421400590958205

This article was downloaded by: [University of Auckland Library]
On: 12 December 2014, At: 03:41
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Molecular Crystals and Liquid
Crystals
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gmcl20
Hydrogen Bonding in
Glyoxylamides
David StC. Black a , Glenn C. Condie a , Donald C.
Craig a & Darryl B. McConnell a
a School of Chemistry , The University of New South
Wales , Sydney, Australia
Published online: 31 Aug 2006.
To cite this article: David StC. Black , Glenn C. Condie , Donald C. Craig & Darryl B.
McConnell (2005) Hydrogen Bonding in Glyoxylamides, Molecular Crystals and Liquid
Crystals, 440:1, 141-146, DOI: 10.1080/15421400590958205
To link to this article: http://dx.doi.org/10.1080/15421400590958205
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.

This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Mol. Cryst. Liq. Cryst., Vol. 440, pp. 141–146, 2005
Copyright # Taylor & Francis Inc.
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421400590958205
Hydrogen Bonding in Glyoxylamides
David StC. Black
Glenn C. Condie
Donald C. Craig
Darryl B. McConnell
School of Chemistry, The University of New South Wales,
Sydney, Australia
A range of secondary 2-amidophenylglyoxylamides self-assemble by intermolecu-
lar hydrogen bonding between the secondary amide proton and the 2-amidophenyl
carbonyl oxygen atom.
Keywords: amides; hydrogen bonding; self-assembled dimers; X-ray crystal structures
The glyoxylamide structural fragment has been shown to display
rather different hydrogen bonding features from simple amides. Pri-
mary and secondary amides usually form tape networks and chain
motifs respectively. However, the primary and secondary indol-2-
ylglyoxylamides 1,2 undergo self-assembly to give dimeric structures
exhibiting new hydrogen bond motifs [1]. On the other hand, the
related tertiary indol-7-ylglyoxylamide 3 dimerises as the result of
unique intermolecular hydrogen bonding, which makes use of p-hydro-
gen bonds from the indole NH to an amide carbonyl acceptor [2].
Address correspondence to David StC. Black, School of Chemistry, The University of
New South Wales, Sydney 2052, Australia. E-mail: d.black@unsw.edu.au
141

142
D. StC. Black et al.
SCHEME 1 The synthesis of 2-amidoglyoxylamides from N-acylisatins.
The formation of hydrogen bonded dimers by the self-assembly of
pyridones [3], homo-peptides [4] and amido-lactams [5] has been
reported earlier. We now report that a range of simple 2-amidophenyl-
glyoxylamides also self-assemble by intermolecular hydrogen bonding,
but in a completely different way from the glyoxylamides 1 and 2. The
2-amidophenylglyoxylamides can be readily synthesized by the nucleo-
philic addition of amines to N-acylisatins [6] (Scheme 1).
The tertiary 20-amidophenylglyoxylamide, N-[2-(oxo-1-piperidinyl-
acetyl)phenyl]acetamide 3 exists as a monomer in the solid state, which
is not unexpected since there is only a single free amide NH proton
available for hydrogen bonding and that proton is strongly hydrogen
bonded to the a-carbonyl oxygen atom forming a six-membered ring
S(6). The crystal structure of glyoxylamide 3 shows the strong intra-
molecular hydrogen bonding between the C20 amido NH proton and
the a-carbonyl oxygen. Another interesting feature is that the tor-
sional angle O2-C9-C10-O3 about the glyoxyl moiety is –94.8ꢀ. The
1H NMR spectrum of glyoxylamide 3 displays a highly deshielded
NH proton at 11.29 ppm belonging to the acetamide.
The secondary 20-benzamidophenylglyoxylamide 4 was observed to
exist as dimer in the solid state. Each monomer unit retains the strong

Hydrogen Bonding in Glyoxylamides
143
intramolecular hydrogen bond S(6), evident in the tertiary derivative,
and in this case, the torsional angle O2-C14-C15-O3 about the glyoxyl
moiety is –89.1ꢀ. The X-ray crystal structure is shown in Figure 1
Dimerization of the secondary derivative exists through intermole-
cular hydrogen bonds between the C20 amide carbonyl oxygen atom
and the glyoxylamide NH proton, forming an eighteen membered ring,
2
2
R ð18Þ, which was not possible in the tertiary derivative. Each mono-
mer contains an approximately planar portion encompassing the C20
amide, the central phenyl ring, and the a-carbonyl group. With respect
FIGURE 1 X-ray crystal structure of compound 4.

144
D. StC. Black et al.
to this planarity, the two monomers are antiparallel, head to tail, one
above the other and offset, suggesting a p–p interaction.
The 1H NMR spectrum of glyoxylamide 4 displays a highly
deshielded NH proton at 11.97 ppm, belonging to the benzamide,
shifted even further downfield than the acetamide NH proton of
glyoxylamide 3. The glyoxylamide NH proton is present at 7.02 ppm
due to its involvement in the S(6) motif.
The self-assembly dimerisation was found to be quite general for
secondary glyoxylamides and examples such as compounds 5–12 have
been prepared.
The crystal structure (Fig. 2) of an imine derivative 5, prepared via
addition of n-butylamine to the related glyoxylamide, or alternatively
by the addition of two equivalents of n-butylamine to N-benzoylisatin,
2
2
also shows dimer formation, with an eighteen-membered ring R ð18Þ.

Hydrogen Bonding in Glyoxylamides
145
FIGURE 2 X-ray crystal structure of compound 5.
Each monomer retains the strong intramolecular hydrogen bond,
thus forming a six-membered ring, S(6), however in this case the
acceptor is an imine. The presence of the imine seems to make little
difference to the hydrogen bonding and the torsional angle N3-C14-
C15-O2 about the glyoxyl moiety is 81.0ꢀ, slightly rotated from an
expected 90ꢀ. Dimerization again exists through intermolecular hydro-
gen bonds between the C20 amide carbonyl oxygen atom and the glyoxyl-
2
2
amide NH proton, R ð18Þ.
The primary 20-amidophenylglyoxylamide, 20-acetamidophenyl-
glyoxylamide 14 was prepared but a suitable crystal could not be
obtained. It is possible that the primary amide derivative could exhi-
bit further inter- and intra-molecular hydrogen bonding and might
1
therefore exist as an aggregate of dimer 15. The H NMR spectrum
of the primary amide 14 indicates that the C20 amide NH proton,
at 10.90 ppm, is strongly intramolecularly hydrogen bonded to the
a-carbonyl group, suggesting the presence of the S(6) motif. The
primary amide NH protons are not equivalent, and two very broad
signals are observed at 6.66 and 5.66 ppm, indicating that each
is uniquely hydrogen bonded. Of these two, the downfield NH
proton is likely to be involved in a hydrogen bonded system. It
is unclear to what extent the upfield proton is also involved in
hydrogen bonding.

146
D. StC. Black et al.
It is possible that the construction of suitable dimeric secondary
glyoxylamides could allow the formation of polymeric self-assembled
structures. The 2-ureido-4-pyrimidone moiety, with its array of four
parallel hydrogen bonds, exists as a self-assembled polymer 16 [6].
REFERENCES
[1] Black, D. StC., Craig, D. C., & McConnell, D. B. (1996). The indol-2-ylglyoxylamide
moiety: A new building block for the design and self-assembly of hydrogen bond net-
works. J. Am. Chem. Soc., 118, 8148–8149.
[2] Black, D. StC., Craig, D. C., & McConnell, D. B. (1997). Self-assembly of an indolyl-
glyoxylamide by unusual hydrogen bonding. Tetrahedron Lett., 38, 4287–4290.
[3] Ducharme, Y. & Wuest, J. D. (1988). Use of hydrogen bonds to control molecular
aggregation. Extensive, complementary arrays of donors and acceptors. J. Org.
Chem., 53, 5787–5789.
[4] Bisson, A. P. & Hunter, C. A. (1996). Cooperativity in the assembly of zipper com-
plexes. Chem. Commun., 1723–1724.
[5] Nadin, A., Derrer, S., McGeary, R. P., Goodman, J. M., Raithby, P. R., Holmes, A. B.,
O’Hanlon, P. J., & Pearson, N. D. (1995). Seven-membered lactams as constraints for
amide self-recognition. J. Am. Chem. Soc., 117, 9768–9769.
[6] Sijbesma, R. P., Beijer, F. H., Brunsveld, L., Folmer, B. J. B., Hirschberg, J. J. K. K.,
Lange, R. F. M., Lowe, J. K. L., & Meijer, E. W. (1997). Reversible polymers formed
from self-complementary monomers using quadruple hydrogen bonding. Science,
278, 1601–1604.