1226
C. K. Lee, J. S. Yu and Y. R. Ji
Vol. 39
indicate that the chemical shift of N-H is solely influenced
by the electronic effect of m- and p-substituted phenyl
ring. On the other hand, the chemical shifts of other amidic
signals in 1 and 3 are essentially δ 3.32 ± 0.02 and they
showed no correlation.
The two N-H signals are the result of rotamers such as
VII and VIII. It is also conceivable that conformations
such as IX and X may cause the appearance of the two
N-H signals. However, it has been known that the
conformation like VII is the most favorable energetically
amide group than meta- and para-Hs. Much larger values
of the slopes of N-H, ortho-H and para-H in Table 1 are
consistent with such rationale.
In conclusion, the nmr spectra of anilides of benzoic
acid, 2-thienoic acid, and 2-furoic acid show good
correlation with the Hammett σ. The plot of the chemical
shift values of the 2-thienanilides or 2-furanilides against
those of the benzanilides provides relative magnitude of
aromaticity indices. Values of 0.79 and 0.52 were obtained
for thiophene and furan, respectively.
[13].
The presence of such rotamers was confirmed by the
EXPERIMENTAL
13C nmr spectra, as listed in Table 3. Not only the carbonyl
carbon, but also the ipso-C of the aroyl ring and the ipso-
and ortho-C's in the anilino ring show distinctive peaks
corresponding the minor rotamers.
The rotational barrier of the C-N bond of an amide is
about 12-25 kcal/mole [14]. For monosubstituted
acetanilide, the more stable conformer is the one with
phenyl group cis to the carbonyl oxygen [15]. In order
to examine the nature of the two distinctive N-H signals
in 1-3 we prepared N-cyclohexylbenzamide (4),
N-cyclohexyl-2-thienamide (5), and N-cyclohexyl-2-
furamide (6) and obtained their nmr spectra in 0.1 M
Melting points were determined on a Fischer MEL-TEMP
apparatus and are uncorrected. Nuclear magnetic resonance
(nmr) spectra were recorded on a Bruker DPX-400 FT NMR
spectrometer in the Central Lab of Kangwon National
University at 400 MHz for H and 100 MHz for 13C and were
referenced to tetramethylsilane. The concentration of the
solution was 0.10 M in dimethyl sulfoxide-d6 and chloro-
form-d. The Central Lab of Kangwon National University
performed elemental analyses.
1
An Illustrative Procedure for Preparation of m- and p-Substituted
Anilides 1-3.
solutions of dimethyl sulfoxide-d . For the purpose of
A mixture of a carboxylic acid (8 mmoles) and thionyl
chloride (28 mmoles) was heated at reflux for 30 minutes. The
resulting solution was evaporated under aspirator pressure to
remove excess thionyl chloride. The residual liquid was cooled in
an ice-water bath and a solution of substituted aniline
6
comparison, the nmr spectra of N-methylbenzamide (7)
and acetanilide (8) were also obtained at 0.1 M dimethyl
sulfoxide-d6 and the resulting values are listed in
Table 6.
(
(
16 mmoles) and triethylamine (10 mmoles) in dichloromethane
15 ml) was added slowly. The solution was heated at reflux for
There was no signal corresponding to different
rotamers of 4-8 in either 1H or C nmr spectra.
Replacement of the phenyl group with a cyclohexyl
group causes upfield shift of the protons in the aroyl ring
by 0.09-0.13 ppm in 4 and 0.10-0.26 ppm in 5 and 6.
Usually ortho-H's are affected most. More importantly,
the N-H signals appear at δ 8.00-8.20 as doublets with
coupling constant of ca. 8 Hz. This means that the
replacement causes the N-H signal shift to upfield by
more than 2 ppm. The N-H signal of acetanilide (8)
appears at δ 9.91 as a sharp singlet whereas it appears at
δ 8.42 as a broad singlet in the case of N-methylbenza-
mide (7). The methyl signal appears as a doublet at δ 2.79
with a coupling constant of 4.6 Hz.
13
1
hour. It was then treated with saturated sodium bicarbonate
solution until the aqueous layer was slightly basic (pH ~8). The
organic layer was washed with water (10 ml) and dried over
anhydrous sodium sulfate. The solvent was removed and the
resulting solid was recrystallized from ethanol. The yields, mp,
and elemental analyses data are listed in Table 7.
An Illustrative Procedure for Preparation of N-Cyclohexyl
Amides 4-6.
A solution of cyclohexylamine (4 mmoles) and triethylamine
(4 mmoles) in dichloromethane (10 ml) was added drop-wise to
an ice-cold solution of acyl chloride (3 mmoles) in dichloro-
methane (10 ml). The resulting solution was heated at reflux for 1
hour. The solution was partitioned in dichloromethane (30 ml)
and water (50 ml). The organic layer was separated, dried over
sodium sulfate, and evaporated. The residue was recrystallized
from ethanol. The yields, mp, and elemental analysis data are
listed in Table 7.
The chemical shift of N-H in rotamer VIII seems to be
much more influenced by the concentration than that of
VII as shown in Table 1. As the concentration increases,
the amide group may form intermolecular hydrogen
bonding like in XI, which causes the down field shift. Such
dimerization is not feasible in rotamer VII. The
intermolecular hydrogen bonding like in XII may be
possible with the rotamer VII. Such hydrogen bonding
should affect the chemical shift of N-H and ortho-H
because they are closer to the electronic influence of the
Acknowledgments.
We thank Dr. Gary Kwong of the 3M Co. and Dr. Michael
Haukaas of the University of Minnesota for help in preparing the
manuscript. The Basic Science Research Institute Program of the
Ministry of Education (BSRI-1997-015-D00003) supported this
research.