Hydrogen bonding in aromatic formamides

Article abstract of DOI:10.1007/s10870-005-6269-3

The solid state structures of two p-substituted aromatic formamides have been determined. p-Nitro formamido benzene (1) crystallizes in the monoclinic space group C2/c with a = 10.9859(7), b = 10.0576(7), c = 13.0331(9) A, β = 97.148(1)° and Z = 8. p-formamido anisole (2) crystallizes in the orthorhombic space group Pna2₁ with a = 10.5598(7), b = 7.6553(5), c = 9.2522(6) A and Z = 4. Both compounds show hydrogen bonding in the solid state, forming infinite chains via N-H...O = C bridges. For the anisole formamide (2), the molecules exhibit in a zig-zag arrangement. The nitro compound (1) exhibits a spiral-like wavy line with a fourfold repeating unit, making it the first formamide having a chiral N-H...O bridged chain reminiscent of those found for α-helices in proteins. While the individual spirals of 1 are orientated either clockwise or counterclockwise, their orientation towards each other is random.

Full text of DOI:10.1007/s10870-005-6269-3

Journal of Chemical Crystallography, Vol. 35, No. 9, September 2005 (ꢀC 2005)
DOI: 10.1007/s10870-005-6269-3
Hydrogen bonding in aromatic formamides
(
1)
(1)
(1)
(1)
Matthias Zeller, Robert J. Wilcox, Floyd G. Snyder III, Harry A. Seibel II,
(1)
(1),∗
Nathan J. Takas, and Allen D. Hunter
Received and accepted June 24, 2003
The solid state structures of two p-substituted aromatic formamides have been determined.
p-Nitro formamido benzene (1) crystallizes in the monoclinic space group C2/c with a =
˚
◦
1
0.9859(7), b = 10.0576(7), c = 13.0331(9) A, β = 97.148(1) and Z = 8. p-formamido
anisole (2) crystallizes in the orthorhombic space group Pna21 with a = 10.5598(7), b =
˚
7
.6553(5), c = 9.2522(6) A and Z = 4. Both compounds show hydrogen bonding in the
solid state, forming infinite chains via N--- H···O=C bridges. For the anisole formamide (2),
the molecules exhibit in a zig-zag arrangement. The nitro compound (1) exhibits a spiral-
like wavy line with a fourfold repeating unit, making it the first formamide having a chiral
N--- H···O bridged chain reminiscent of those found for α-helices in proteins. While the
individual spirals of 1 are orientated either clockwise or counterclockwise, their orientation
towards each other is random.
KEY WORDS: Formamides; hydrogen bonding; disorder; infinite chain; spiral; disorder.
Introduction
The need for a simplified model for biolog-
ical macromolecules such as proteins is evident.
When polypeptides fold into proteins, dimers
This model has to contain both C -- -- -- O and N---H
units which are able to form N---H···O hydro-
gen bonds, and formamide, the smallest model
to meet these requirements, becomes an obvious
choice. In several computational-structural stud-
ies, monomeric and dimeric formamides were
compared with one and two dimensional for-
mamide chains as models for α-helices and
and chains of N---H···O amide hydrogen bonds
are formed in various secondary structural mo-
1
tifs such as pleated β-sheets and α-helices. In
computational studies, these hydrogen bonds have
usually been modeled by pair wise interactions
between individual hydrogen bond donors and
acceptors. Using these effective two-body inter-
actions it was possible in some cases to simu-
late the actual many-body problem. However, it is
becoming increasingly apparent that cooperative
interactions involving many molecules have to be
4
β-pleated sheets in proteins. One study on H-
bonded formamide chains of various lengths re-
vealed that the strength of internal hydrogen
bonds in chains may be up to 2.5 times larger
2,3
5
taken into account.
than that in an isolated dimer. This emphasizes
again the need for the incorporation of cooperative
effects.
While formamide was successfully applied
as a model compound in computational studies,
it may not be the best choice as a real structural
(
1)
Youngstown State University, Department of Chemistry, One
University Plaza, Youngstown, OH 44555-3663, USA.
To whom correspondence should be addressed; e-mail: adhunter@
ysu.edu.
∗
7
23
1
074-1542/05/0900-0723/0 ꢀC 2005 Springer Science+Business Media, Inc.

724
Zeller, Wilcox, Snyder, Seibel, Takas, and Hunter
model for proteins. In particular, formamide it-
only 4 hydrogen bonded dimers, in contrast to
39 chain like hydrogen bonded networks (12 of
type (b) and 27 of type (c)). The chain like struc-
tures (b) and (c) can serve as models for the
hydrogen bonding networks found in pleated β-
sheets, and form (c) resembles very closely the
motif found in antiparallel β-pleated sheets. How-
ever, having repeating units of only one or two,
neither motifs (b) nor (c) are good models for α-
self has an unsubstituted NH group with two
2
hydrogen atoms per amino group being available
for hydrogen bonding. It therefore does not form
chains in the solid state. Instead, its structure
is composed of puckered layers and each layer
can be described either as being built from al-
ternating zig-zag chains or from cyclic dimers of
6
the HCONH unit. The hydrogen bonds within
2
8
the zig-zag chains seem to be stronger than those
within the cyclic dimers, as is reflected by the
N---H···O bond lengths of 2.88 and 2.93 A, re-
helices since they lack the chiral characteristics
of α-helices where each formamide unit is turned
◦
˚
---
by 40 while the N H···O chains spiral around
spectively. Proteins have only one amino hydro-
gen atom per formamide unit and the formation
of multiple hydrogen bonds per amino group is
therefore not possible. Thus, when looking for a
structural model for the formation of hydrogen
bonds in proteins N-substituted formamides may
be a better choice.
the center of the α-helix.
In this context, we report two X-ray struc-
tures of aromatic formamides. By changing the
substituent in their para-positions from a methoxy
to a nitro group, a distinctive change of the hy-
drogen bonding arrangement is observed. In ad-
dition, p-nitro formamido benzene is the first
structurally characterized formamide exhibiting a
chiral spiral-like N---H···O chain similar to those
To date three types of hydrogen bonding in-
teractions have been found in N-substituted for-
mamides: dimers and two types of chains with
N---H···O bridges (Scheme 1). The chains are
found in an α-helices.
much more prevalent than dimers, and a search
Experimental
7
of the Cambridge Structural Database revealed
The title compounds were synthesized from
the amines by heating them at reflux in a solu-
tion of 80% formic acid for 1 hour. p-nitro for-
mamido benzene was precipitated with water, fil-
tered off, washed with water until neutral, dried
in vacuo, and recrystallized from hot acetone to
get a yellow microcrystalline powder. Single crys-
◦
tals were grown from acetone by cooling to 0 C.
p-Formamido anisole was extracted from the
formic acid solution with ether. The ether extract
was dried with MgSO and the compound was
4
crystallized from ether and recrystallized twice to
get pale purple crystals.
Diffraction data of both compounds have
been collected with a ‘Bruker AXS SMART
APEX CCD’ diffractometer at 100 K using
monochromated Mo Kα radiation with the omega
scan technique. The unit cell was determined
Scheme 1. Hydrogen bond interactions found for N-
substituted formamides in the solid state. (a) formamide
dimers (b) chains with a repeating unit of one molecule
9
using SAINT+ and the structure was solved
by direct methods and refined by full matrix
(c) chains with a repeating unit of two (every second molecule
2
is rotated with respect to the preceding one).
least squares against F with all reflections

Hydrogen bonding in aromatic formamides
725
9
summarize selected bond lengths and angles of
the molecules. The nitro formamido benzene (1)
shows a flip-flop disorder of the formamido group
using SHELXTL. Refinement of an extinction
coefficient was found to be insignificant. All non-
hydrogen atoms were refined anisotropically. Hy-
drogen atom positions were taken from the differ-
ence Fourier map and were refined isotropically.
Compound (1) exhibits a flipping disorder for the
formamido substituent, and the N---H and C---H
bond lengths in both disordered fragments have
been restrained to be equal with an effective stan-
dard deviation of 0.02 using the SADI command.
The occupancies were found to be 1:1. Crystal
data and experimental details are listed in Table 1.
(
Fig. 1), with the occupancies being each one
half.
Neither molecule is perfectly planar and the
functional groups are not totally in the planes of
the benzene rings. For the nitro derivative (1),
the deviation is less pronounced and the aver-
age torsion angle of the formamido group with
◦
the aromatic ring is 8.2(4) . The torsion angle
of the nitro group towards the aromatic ring
◦
is 16.0(2) . For 1, a substantial conjugation of
both the nitro and the formamido group with the
π-orbitals of the benzene ring can be assumed.
For the anisole derivative (2), the torsion angle
Results and discussion
◦
Molecular representations of both molecules
of the methoxy group is similar (11.7(1) ), but
are shown in Figs. 1 and 2. Tables 2 and 3
the average torsion angle of the formamido group
Table 1. Crystal Data and Structure Refinement of 1 and 2
Empirical formula
Formula weight
Solvent
C7H6N2O3
166.14
Acetone
Yellow fragment
100(2)
Monoclinic
C2/c
C8H9NO2
151.16
Diethylether
Pale purple fragment
100(2)
Crystal habit
Temperature (K)
Crystal system
Space group
Orthorhombic
Pna21
Unit cell dimensions
˚
a (A)
10.9859(7)
10.0576(7)
13.0331(9)
97.148(1)
1428.86(17)
8
10.5598(7)
7.6553(5)
9.2511(6)
˚
b (A)
˚
c (A)
◦
β ( )
˚
3
Volume (A )
747.84(8)
4
1.343
Z
Density (calculated, g cm 3)
Absorption coefficient (mm 1)
−
1.545
0.124
−
0.097
F(0 0 0)
688
320
Crystal size (mm)
θ range for data collection ( )
Index ranges
0.40 × 0.36 × 0.15
2.76–28.31
–14 ≤ h ≤ 14,
0.5 × 0.30 × 0.18
3.29–28.30
–14 ≤ h ≤ 14,
–10 ≤ k ≤ 10,
–12 ≤ l ≤ 12
7279
◦
–
–
13 ≤ k ≤ 10,
17 ≤ l ≤ 17
Reflections collected
7118
Independent reflections
Reflections with I > 2 σ(I)
Absorption correction
Min./max. transmission
Data/restraints/parameters
1766 [Rint = 0.0248]
1855 [Rint = 0.0267]
1722
1815
Semiempirical from multi scans Semiempirical from multi scans
0.8367/0.9800
1766/2/160
1.170
0.786/0.980
1855/1/136
1.075
2
Goodness-of-fit on F
Final R indices [I > 2σ(I)]
R indices (all data)
Largest diff. peak and hole (eA
R1 = 0.0431, wR2 = 0.1154
R1 = 0.0436, wR2 = 0.1158
0.383 and –0.424
R1 = 0.0314, wR2 = 0.0836
R1 = 0.0320, wR2 = 0.0840
0.263 and –0.171
˚
−3
)

726
Zeller, Wilcox, Snyder, Seibel, Takas, and Hunter
Fig. 1. ORTEP representation of 1, ellipsoids at 50% probability. The occupancy ratio
for the disordered fragments is 1:1.
◦
with the benzene ring is 27.49(6) , thus reducing
the effective conjugation of the π-orbitals of for-
mamido and aromatic moieties by about 50%
compared to the coplanar case.
For the nitro formamido benzene (1), the
hydrogen bonding situation is more compli-
cated. The occupancies of the flip-flop disor-
dered formamide groups is 1:1. In order to avoid
overlap of the formamide groups of neighbor-
ing molecules, the orientation of the disordered
formamide groups cannot be random, but every
second molecule in the N---H···O chains has to
Both molecules form hydrogen bonded in-
finite chains in the solid state. For the anisole
derivative (2), a zig-zag arrangement is found
similar to those found for most other formamide
derivatives (see Fig. 3). The N---H···O bonding
be oriented in the opposite direction. This results
in the formation of an infinite chain with a four-
fold repeating unit (see Fig. 4). The N---H···O
˚
distance is 2.830(2) A which is in the usual range
and is only slightly shorter than observed for the
zig-zag chains of formamide itself. The value
6
˚
distances in (1) are 2.924(2) and 2.860(2) A, re-
for the H···O hydrogen bonding distance itself is
spectively, and the corresponding H···O hydrogen
˚
˚
bonding distances are 1.977(38) and 1.983(35) A.
2
.025(21) A.
Fig. 2. ORTEP representation of 2, ellipsoids at 50% probability.

Hydrogen bonding in aromatic formamides
727
˚
˚
Table 2. Selected Bond Lengths (A) and
Table 3. Selected Bond Lengths [A]
◦
◦
Angles ( ) for 1.
and Angles [ ] for 2.
˚
˚
Bond lengths (A)
N(2) ---- C(7 )
Bond lengths (A)
ꢁ
1.245(3)
1.308(3)
0.95(3)
0.94(3)
1.222(3)
1.221(3)
0.98(2)
0.99(2)
1.4022(16)
1.3825(19)
1.3891(18)
1.4007(17)
1.4015(17)
1.3853(17)
1.3873(17)
1.2322(15)
1.2343(15)
1.4608(16)
N(1) ---- C(1)
N(1) ---- C(2)
N(1) ---- H(2)
O(2) ---- C(5)
O(2) ---- C(8)
C(2) ---- C(3)
C(2) ---- C(7)
C(5) ---- C(6)
C(5) ---- C(4)
C(7) ---- C(6)
C(4) ---- C(3)
O(1) ---- C(1)
C(1) ---- H(1)
1.3377(16)
1.4203(15)
0.82(2)
N(2) ---- C(7)
N(2) ---- H(8)
ꢁ
N(2) ---- H(8 )
1.3678(14)
1.4313(15)
1.3924(15)
1.3983(16)
1.3932(16)
1.3948(17)
1.3832(17)
1.3916(17)
1.2297(16)
0.936(18)
C(7) ---- O(3)
ꢁ
ꢁ
C(7 ) ---- O(3 )
C(7) ---- H(7)
ꢁ
ꢁ
C(7 ) ---- H(7 )
N(2) ---- C(4)
C(2) ---- C(3)
C(2) ---- C(1)
C(4) ---- C(5)
C(4) ---- C(3)
C(1) ---- C(6)
C(6) ---- C(5)
N(1) ---- O(1)
N(1) ---- O(2)
N(1) ---- C(1)
◦
Bond angles ( )
C(1) ---- N(1) ---- C(2)
C(1) ---- N(1) ---- H(2)
C(2) ---- N(1) ---- H(2)
C(5) ---- O(2) ---- C(8)
C(3) ---- C(2) ---- C(7)
C(3) ---- C(2) ---- N(1)
C(7) ---- C(2) ---- N(1)
O(2) ---- C(5) ---- C(6)
O(2) ---- C(5) ---- C(4)
C(6) ---- C(5) ---- C(4)
C(6) ---- C(7) ---- C(2)
C(3) ---- C(4) ---- C(5)
C(4) ---- C(3) ---- C(2)
C(7) ---- C(6) ---- C(5)
O(1) ---- C(1) ---- N(1)
O(1) ---- C(1) ---- H(1)
N(1) ---- C(1) ---- H(1)
126.53(11)
116.1(14)
117.1(13)
116.83(10)
119.45(10)
118.44(10)
122.08(10)
115.53(10)
124.69(10)
119.78(11)
119.71(10)
119.34(11)
120.88(10)
120.80(11)
126.30(12)
119.3(12)
114.4(12)
◦
Bond angles ( )
C(7 ) ---- N(2) ---- C(4)
C(7) ---- N(2) ---- C(4)
C(7) ---- N(2) ---- H(8)
C(7 ) ---- N(2) ---- H(8 )
ꢁ
134.27(18)
136.73(17)
112(3)
ꢁ
ꢁ
120(3)
105(3)
111(3)
ꢁ
C(4) ---- N(2) ---- H(8 )
C(4) ---- N(2) ---- H(8)
O(1) ---- N(1) ---- O(2)
O(1) ---- N(1) ---- C(1)
O(2) ---- N(1) ---- C(1)
C(3) ---- C(2) ---- C(1)
C(5) ---- C(4) ---- C(3)
C(5) ---- C(4) ---- N(2)
C(3) ---- C(4) ---- N(2)
C(6) ---- C(1) ---- C(2)
C(6) ---- C(1) ---- N(1)
C(2) ---- C(1) ---- N(1)
C(1) ---- C(6) ---- C(5)
C(6) ---- C(5) ---- C(4)
C(2) ---- C(3) ---- C(4)
O(3) ---- C(7) ---- N(2)
O(3) ---- C(7) ---- H(7)
N(2) ---- C(7) ---- H(7)
O(3) ---- C(7) ---- H(7 )
N(2) ---- C(7) ---- H(7 )
H(7) ---- C(7) ---- H(7 )
O(3) ---- C(7) ---- H(8 )
N(2) ---- C(7) ---- H(8 )
C(7) ---- O(3) ---- H(8 )
O(3 ) ---- C(7 ) ---- N(2)
O(3 ) ---- C(7 ) ---- H(7 )
123.27(12)
118.55(11)
118.17(11)
118.77(12)
120.15(11)
119.61(11)
120.25(12)
122.41(12)
118.56(11)
119.03(11)
118.71(11)
119.95(11)
120.01(12)
121.9(2)
122(2)
In contrast to the hydrogen bonded chains
formed by α-helices in proteins, 1 does not form
real spirals. Instead, all of the formamide units
are located roughly in one plane (Fig. 5) and
the hydrogen bonds exhibit a wavy line shape
(Fig. 4). The aromatic substituents are sticking
out above and below that plane (Fig. 5). This,
combined with the polar directionality on the
hydrogen bonded chain, makes each individual
chain chiral and the wavy line has to be described
as rotating either clockwise or counterclockwise.
The space group of 1 is C2/c, which is not chi-
ral, and the achirality of the crystal as a whole
can thus only be explained by assuming that the
orientation of each individual spiral like chain
must be random, while that of the formamido
116(2)
ꢁ
ꢁ
ꢁ
ꢁ
158.8(10)
78.3(10)
38(2)
79(3)
44(3)
33(2)
ꢁ
ꢁ
ꢁ
ꢁ
125.0(3)
128.0(19)
106.9(19)
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
N(2) ---- C(7 ) ---- H(7 )

728
Zeller, Wilcox, Snyder, Seibel, Takas, and Hunter
Fig. 3. Representation of the hydrogen binding in 2. The hydrogen bond chain is aligned
along the c-axis.
Fig. 4. Representation of the hydrogen binding in 1. The hydrogen bond chain is aligned
along the c-axis.

Hydrogen bonding in aromatic formamides
729
Fig. 5. Representation of the hydrogen binding in 1 showing the plane formed by the
hydrogen bonded formamide units and the aromatic substituents pointing above and
below the plane. View along the c-axis.
groups within each wavy chain is determined
by the orientation of the neighboring molecules
along the chain. This results in a random one
to one occupation of the disordered formamido
orientations with the individual spiral-like wavy
chains being eitherclockwiseorcounterclockwise
oriented.
funded by NSF Grant No. 0087210, by Ohio Board of
Regents Grant CAP-491, and by YSU.
References
1. (a) Dobson, C.M.; ali, A.; Karplus, M. Angew. Chem., Int. Ed.
1
7
998, 37, 868–893. (b) Dill, K.A. Biochemistry 1990, 29, 7133–
155; (c) Accounts of Chemical Research, 1998, 31(11), entire
issue.
2
. van der Vaart, A.; Bursulaya, B.D.; Brooks, C.L., III; Merz, K.M.,
Jr. J. Phys. Chem. B 2000, 194, 9554.
Supplementary material CCDC-215451 and CCDC 215452
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge at www.ccdc.cam.
ac.uk/conts/retrieving.html [or from the Cambridge Crystallo-
graphic Data Center (CCDC), 12 Union Road, Cambridge CB2
3. Vendruscolo, M.; Domany, E. J. Chem. Phys. 1998, 109, 11101–
1
1108.
4
5
. Suhai, S. J. Phys. Chem. 1996, 100, 3950–3958.
. Kobko, N.; Paraskevas, L.; del Rio, E.; Dannenberg, J.J. J. Am.
Chem. Soc. 2001, 123, 4348.
1EZ, UK; fax: +44(0)1223-336033; email: deposit@ccdc.cam.
6. (a) Ladell, J.; Post, B. Acta Cryst. 1954, 7, 559. (b) Torrie, B.H.;
O’Donovan, C.; Powell, B.M. Molecular Physics 1994, 82(4),
ac.uk].
6
43–649.
7
. Conquest Version 1.5, Copyright CCDC 2002. Databases used:
CSD version 5.24 (November 2002) + Updates Feb, Apr and Jul
Acknowledgments
2
003.
8
9
. Stryer, L. Biochemistry; 4th edn; W. H. Freeman and Company:
MZ was supported by NSF Grant No. 0111511,
RJW, FGS, and HAS by NSF Grant No. 0097682, NJT
by NSF Grant No. 0128154, and the diffractometer was
New York, 1995, p. 28–32.
. Bruker (1997). SAINT (Version 6.02), SMART for WNT/2000
(
Version 5.625) and SHELXTL. Bruker AXS Inc., Madison,
Wisconsin, USA.