Linear-to-turn conformational switching induced by deprotonation of unsymmetrically linked phenolic oligoamides

Article abstract of DOI:10.1002/anie.200461842

Proton-triggered conformational switching: Unsymmetrically linked phenolic oligoamides fold into a turn conformation from a linear conformation following the deprotonation of the phenol groups (see scheme). Deprotonation induces a rearrangement of the hyd

Full text of DOI:10.1002/anie.200461842

Angewandte
Chemie
conformation through hydrogen bonds.[12,13] A rearrangement
of the intramolecular hydrogen bond induced by deprotona-
tion of the phenolic OH group was suggested previously[14]
and established in our recent study on the crystal structures of
protonated and deprotonated salicylamide derivatives
(Scheme 1).[15] From these findings, we believe that oligo-
Scheme 1. Conformational switching of a salicylamide derivative by
deprotonation and protonation. Ar=2-chlorophenyl, X=Br, Y=Cl.
amide compounds that comprise a salicylamide moiety in a
repeating unit have the potential to exhibit conformational
switching with the rearrangement of the intramolecular
hydrogen bond as the driving force of conformational switch-
ing.[9,10] Herein, we report the synthesis and structure
determinations of unsymmetrically linked phenolic oligo-
amides (1–4) that comprise a salicylamide skeleton in a
repeating unit as novel aromatic oligoamide compounds that
undergo a conformational switch.
Oligoamide Conformations
Linear-to-Turn Conformational Switching
Induced by Deprotonation of Unsymmetrically
Linked Phenolic Oligoamides**
The crystal structures of protonated and deprotonated
monomer models, namely, 1’ and (1’ÀH+)ÀMe4N+, which
differ from 1 by the replacement of the tBuCO group by
MeCO, are shown in Figure 1. In 1’, the phenol OH group
Daisuke Kanamori, Taka-aki Okamura,
Hitoshi Yamamoto, and Norikazu Ueyama*
=
forms intramolecular NH···OH and OH···O C hydrogen
bonds with average short distances for O11-N1 and O11-O2
of 2.622 and 2.486 ꢀ, respectively. In the case of
(1’ÀH+)ÀMe4N+, the phenolate oxygen anion forms double
intramolecular NH···O(oxyanion) hydrogen bonds with short
distances for O11-N1 and O11-N2 of 2.605(2) and 2.643(2) ꢀ.
The C-terminal N-tert-butylcarbamoyl substituent forms two
different types of hydrogen bonds which means that the
deprotonation of the phenol OH group induces a conforma-
Aromatic oligoamide compounds attract much attention
because they form highly ordered structures with intra-
molecular hydrogen bonds.[1–8] In particular, control of con-
formational switching within a molecule could lead to the
development of molecular machines.[9–11] Salicylamide deriv-
atives are well known to form a highly ordered, planar
À
tional change (ꢀ 1808 rotation about the C12 C2 bond) that
[*] D. Kanamori, Dr. T.-a. Okamura, Dr. H. Yamamoto, Prof. N. Ueyama
Department of Macromolecular Science
Graduate School of Science
leads from a linear-to-turn conformational switching in longer
oligoamides. This type of conformational switching was
established in our previous study with other salicylamide
derivatives (Scheme 1).[15] Intermolecular interactions were
Osaka University
Toyonaka, Osaka, 560-0043 (Japan)
Fax: (+81)6-6850-5474
=
found in 1’ only as NH···O C hydrogen bonds.
E-mail: ueyama@chem.sci.osaka-u.ac.jp
Molecular structures of the dimer in protonated and
deprotonated forms, 2 and (2À2H+)2À(Et4N+)2, are shown in
Figure 2. In 2, each phenol OH group forms intramolecular
[**] D.K. expresses his special thanks to the Center of Excellence
(21COE) program “Creation of Integrated EcoChemistry of Osaka
University”.
=
NH···OH and OH···O C hydrogen bonds that result
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
=
=
in an intramolecular NH···OH···O C-NH···OH···O C hydro-
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DOI: 10.1002/anie.200461842
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Figure 1. Molecular structures of a) 1’ (one of the two crystallographi-
cally independent molecules is shown) and b) (1’ÀH+)ÀMe4N+. Dis-
placement ellipsoids are drawn at the 50% probability level; the tetra-
methylammonium cation is omitted for clarity in (b). Selected bond
lengths, short contacts [ꢀ], and torsion angles [8] for 1’: C11–O11
1.3606(16), O11···N1 2.606(1), O11···O2 2.481(1), C1-N1-C16-C11
170.71(15), N2-C2-C12-C11 À167.69(14). Selected bond lengths, short
contacts [ꢀ], and torsion angles [8] for (1’ÀH+)À: C11–O11 1.297(2),
O11···N1 2.605(2), O11···N2 2.643(2), C1-N1-C16-C11 173.43(14), N2-
C2-C12-C11 7.2(2).
Figure 2. Molecular structures of a) 2 and b) (2À2H+)2À(Et4N+)2. Dis-
placement ellipsoids are drawn at the 50% probability level; solvent
molecules and tetraethylammonium cations are omitted for clarity.
Selected bond lengths, short contacts [ꢀ], and torsion angles [8] for 2:
C11–O11 1.332(9), C21–O21 1.414(10), O11···N1 2.584(9), O11···O2
2.472(9), O21···N2 2.584(9), O21···O3 2.462(8), C1-N1-C16-C11
172.8(9), N2-C2-C12-C11 À172.2(10), C2-N2-C26-C21 178.4(10), N3-
C3-C22-C21 À175.0(8). Selected bond lengths, short contacts [ꢀ], and
torsion angles [8] for (2À2H+)2À: C11–O11 1.268(14), C21–O21
1.339(13), O11···N1 2.50(1), O11···N2 2.64(1), O21···N2 2.72(1),
O21···N3 2.58(1), C1-N1-C16-C11 À176(2), N2-C2-C12-C11 À22(2),
C2-N2-C26-C21 153.2(14), N3-C3-C22-C21 7(2).
gen-bonded chain. A similar mode of hydrogen bonding was
reported
for
3,3’,5,5’,6-pentachloro-2’-hydroxysalicyl-
anilide.[16] In (2À2H+)2À(Et4N+)2, both of the phenolate
oxygen anions form double intramolecular NH···O(oxyanion)
hydrogen bonds. The NH group in the bridging amide group is
involved in a bifurcated intramolecular NH···O(oxyanion)
hydrogen bond. This type of intramolecular hydrogen bond is
classified as a three-center hydrogen bond and is reported to
be strong.[17] Three-center hydrogen-bonded structures are
also known to be almost planar.[3,6,17] However, the crystal
structure of (2À2H+)2À(Et4N+)2 has a slightly distorted
structure that is different from other oligoamides. Because
the optimized structure of simplified (2À2H+)2À is planar,[18]
this slight distortion may be caused by its packing structure.
The difference in the hydrogen-bonding mode between the
hydroxyl or phenoxyl group and the neighboring substituents
on the C-terminal side gives a linear-to-turn conformational
switch. Intermolecular hydrogen bonds are formed in the
changes in the chemical shifts for the OH and NH groups
(within 0.04 ppm) which indicates that intermolecular hydro-
gen bonds are not formed.[3] In the protonated forms of all the
oligoamides, the signals for the phenol OH groups were
observed at significantly low field (d = 12.49–13.36 ppm)
=
which suggests the formation of OH···O C hydrogen bonds.
The signals for the NH protons of the N-terminal and bridging
amide groups were observed at d = 8.24–8.25 and d = 8.99–
9.06 ppm, respectively. These NH signals were shifted slightly
downfield relative to the NH protons in benzanilide (d =
7.76–7.86 ppm),[19] which indicates the formation of
NH···OH hydrogen bonds in the N-terminal and bridging
amide groups. The amide NH protons in the C-terminal amide
groups were observed at d = 6.13 ppm, where signals for non-
hydrogen-bonded NH groups of benzamide derivatives are
usually observed. NOE correlations between amide NH
protons and aryl protons are useful in elucidating the
conformations of aromatic amide compounds, including
salicylamide derivatives.[20] The NH protons, except in the
=
protonated form 2 as NH···O C hydrogen-bonded chains and
not in (2À2H+)2À(Et4N+)2. This behavior is similar to that of
the monomeric protonated pair, 1’ and (1’ÀH+)ÀMe4N+.
Structures of the oligoamides in solution were determined
by 1H NMR spectroscopy of samples dissolved in CDCl3 and
CD3CN (5 mm). Chemical shifts of OH and NH groups
indicate hydrogen-bond formation. Dilution experiments
from 40 to 1 mm for all oligoamides resulted in no significant
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Chemie
N-terminal amide group, show NOE correlations with
neighboring aromatic protons in each unit. If all oligoamides
display a similar mode of hydrogen bonding in solution as that
found in the crystal structures of 1’ and 2, these results are
reasonable. The proposed structure of 4 is depicted in
Scheme 2 with arrows representing the observed NOE
calixarenes, although the conformations of the latter are
observed for the protonated form. Because the pKa values of
each phenol OH group of these oligoamides are lowered by
the intramolecular NH···O(oxyanion) hydrogen bonds,[14,24,25]
the OH protons can completely dissociate, unlike the case of
calixarenes.[26,27] Our results indicate that as a consequence of
lowering the basicity, intramolecular
NH···O(oxyanion) hydrogen bonds
enable phenolate anions to position
themselves close to each other.
Charge delocalization of phenolate
anions supported by the results of
cyclic voltammograms that reveal
that all phenolate anions are in a
mixed-valence state also means a
lowering of the basicity (see Support-
ing Information).
In conclusion, conformational
switching in the unsymmetrically
linked phenolic oligoamides, mono-
mer 1 to tetramer 4, was established
in both the solid (for monomers and
dimers) and solution states. The
deprotonation of a hydroxyl group
in each unit induces a rearrangement
of the hydrogen-bonding mode
Scheme 2. Proposed structures of 4 (linear) and the anionic part of (4À4H+)4À (turn) in solution.
Arrows represent NOE correlations (a represent correlations that are present only in
[D6]DMSO).
1
=
correlations. The similarities in the H NMR spectroscopic
results of all the oligoamides show that the longer oligoamides
also have linear conformations with the same hydrogen-
bonding mode in the protonated forms as shown for 1’ and 2.
For the deprotonated forms of all the oligoamides, the
signals for the NH protons were largely shifted downfield
relative to the corresponding protons in the protonated forms
which suggests strong NH···O(oxyanion) hydrogen-bond
formation. The NH protons in the bridging amide groups
showed the largest downfield shift relative to other NH
protons in each oligoamide. As established in the crystal
structure of (2À2H+)2À(Et4N+)2, the NH proton in the
bridging amide group forms a bifurcated NH···O(oxyanion)
hydrogen bond. The bifurcated hydrogen bond is stronger and
shifts the signal for NH more downfield than a single
hydrogen bond would do.[21] No NOE correlations were
observed for any of the NH protons in CDCl3 or CD3CN. The
results also show that the amide NH protons do not direct to
aromatic protons but rather to phenolate oxygen anions. The
proposed structure of the anion part of (4À4H+)4À(Et4N+)4 is
depicted in Scheme 2. The similarities in the 1H NMR
spectroscopic results for the longer oligoamides to those for
(1’ÀH+)ÀMe4N+ and (2À2H+)2À(Et4N+)2 indicate that the
other oligoamides also adopt the turn conformation in the
deprotonated form with the same hydrogen-bonding mode.
Even in a strong intermolecular hydrogen-bonding sol-
vent, [D6]DMSO,[22] the overall conformations of protonated
and deprotonated forms are maintained because the observed
additional NOE correlations between the NH and aryl
protons are very weak.
within the unit from OH···O C to NH···O(oxyanion), which
leads to linear-to-turn conformational switching.
Experimental Section
X-ray crystal structure analysis: The data were collected at 200 K on a
Rigaku RAXIS-RAPID Imaging Plate diffractometer (MoKa radia-
tion; l = 0.71069 ꢀ for 1’ and 0.71075 ꢀ for others). The structures
were solved by direct methods (SIR92[28] for 1’ and (1’ÀH+)ÀMe4N+
and SIR2002[29] for 2 and SHELXS-97[30] for (2À2H+)2À(Et4N+)2) and
refined by full-matrix least-squares on F2. The non-hydrogen atoms
were refined anisotropically. The coordinates of OH and NH protons
in 1’ were refined by using fixed thermal factors, and the rests were
included in calculated positions. Crystal data for C13H18N2O3 (1’):
0.35 ꢁ 0.35 ꢁ 0.35 mm3, monoclinic, P21/a (#14), a = 16.4062(10), b =
9.9004(7), c = 16.5488(14) ꢀ, b = 92.1580(10)8, V= 2686.1(3) ꢀ3, Z =
8, 1calcd = 1.238 gcmÀ3, m(MoKa) = 0.88 cmÀ1, Mw = 250.29. 6124 reflec-
tions and 349 variables were used to solve the structure, R1 = 0.044,
wR2 = 0.113, GOF (F2) = 1.00. Crystal data for C17H21N3O3
((1’ÀH+)ÀMe4N+): 0.40 ꢁ 0.20 ꢁ 0.10 mm3, monoclinic, P21/n (#14),
a = 6.890(5), b = 15.33(2), c = 18.05(2) ꢀ, b = 93.41(8)8, V=
1904(4) ꢀ3, Z = 4, 1calcd = 1.128 gcmÀ3, m(MoKa) = 0.77 cmÀ1, Mw =
323.43. 4350 reflections and 209 variables were used to solve the
structure, R1 = 0.042, wR2 = 0.095, GOF (F2) = 0.81. Crystal data for
C35H55N3O6 (2·Et2O): 0.30 ꢁ 0.10 ꢁ 0.10 mm3, monoclinic, Cc (#9), a =
16.720(3), b = 10.2219(16), c = 23.907(3) ꢀ, b = 93.248(11)8, V=
4079.4(11) ꢀ3, Z = 4, 1calcd = 0.999 gcmÀ3
,
m(MoKa) = 0.68 cmÀ1
,
Mw = 613.83. 7681 reflections and 427 variables were used to solve
the structure, R1 = 0.077, wR2 = 0.163, GOF (F2) = 0.85. Crystal data
for C49H86N6O5 ((2À2H+)2À(Et4N+)2·CH3CN): 0.20 ꢁ 0.20 ꢁ 0.20 mm3,
monoclinic, P21/c, a = 15.223(12), b = 17.143(13), c = 19.901(14) ꢀ,
b = 101.44(3)8, 5090(7) ꢀ3, Z = 4, 1calcd = 1.095 gcmÀ3
, m(MoKa) =
0.71 cmÀ1, Mw = 839.24. 8946 reflections and 542 variables were
used to solve the structure, R1 = 0.095, wR2 = 0.128, GOF (F2) = 0.74.
CCDC 247765–CCDC 247768 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of charge
In terms of the close proximity of the phenol oxygen
atoms, the turn conformation in the deprotonated form
resembles the conformation of benzoxazine oligomers[23] and
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Communications
from the Cambridge Crystallographic Data Centre via www.ccdc.ca-
m.ac.uk/data_request/cif.
atom, but has methyl groups at the N and C termini in place of
tert-butyl groups. (Gaussian 03, Revision A.1, M. J. Frisch, G. W.
Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheese-
man, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C.
Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B.
Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H.
Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J.
Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H.
Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross,
C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O.
Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y.
Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg,
V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O.
Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B.
Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J.
Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I.
Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham,
C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B.
Johnson, W. Chen, M. W. Wong, C. Gonzalez, and J. A. Pople,
Gaussian, Inc., Pittsburgh PA, 2003.)
Received: August 31, 2004
Revised: October 23, 2004
Published online: December 28, 2004
Keywords: amides · conformation analysis · hydrogen bonds ·
.
protonation
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