Schiff bases of gossypol: An NMR and DFT study

Article abstract of DOI:10.1002/mrc.1532

Schiff bases of gossypol with benzylamine, methylamine, 4-aminoacetophenone and 4-fluoroaniline have been synthesized and characterized by NMR spectroscopy. All the Schiff bases of gossypol are in the enamine form according to ³J(HC,NH) and

Full text of DOI:10.1002/mrc.1532

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2005; 43: 302–308
Published online 27 January 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1532
Schiff bases of gossypol: an NMR and DFT study
Quang Ton That,1 Kim Phi Phung Nguyen2 and Poul Erik Hansen2∗
1
University of Natural Sciences, National University of HoChiMinh City, Vietnam
Department of Life Sciences and Chemistry, Roskilde University, PO Box 260, DK-4000 Roskilde, Denmark
2
Received 2 October 2004; Revised 27 October 2004; Accepted 29 October 2004
Schiff bases of gossypol with benzylamine, methylamine, 4-aminoacetophenone and 4-fluoroaniline have
been synthesized and characterized by NMR spectroscopy. All the Schiff bases of gossypol are in the
enamine form according to 3J(HC,NH) and 1J(N,H) coupling constants. The spectra are basically unchanged
by change of solvent (CD2Cl2, THF-d8 and CD3OD) and by variation of temperature. For the derivative
of benzylamine, deuterium isotope effects on 13C chemical shifts are determined. They support strongly
the enamine form and serve as a reference for other tautomeric Schiff bases. Structures and NMR nuclear
shieldings of model compounds (the second monomer is replaced by a 2-hydroxybenzene ring) have been
calculated by density functional theory (DFT) methods. A good correlation is observed between calculated
13C nuclear shieldings of the enamine form and observed 13C chemical shifts. Copyright  2005 John Wiley
& Sons, Ltd.
KEYWORDS: gossypol; Schiff bases; isotope effects; 13C chemical shifts; 1H NMR; DFT calculations; enamine; 15N–H
coupling constants
1J(N,H) coupling constants and deuterium isotope effects
on 13C chemical shifts are measured to describe the system
with respect to tautomeric vs. non-tautomeric behaviour.
Furthermore, spectra are recorded in solvents of different
polarities and at varying temperature. The main aim is to
find parameters for the enamine form for future use in
describing tautomeric Schiff bases in general.
INTRODUCTION
Schiff bases have attracted much attention because of their
tautomeric properties1–12 (and consequently proton transfer)
and because of interesting biological properties.13–17 Schiff
bases of o-hydroxybenzaldehydes and o-hydroxyacetophen-
ones and, in many cases, the corresponding naphthalene
derivatives have been investigated in great detail.1,3,7,9,11
Structures have been determined both by X-ray18 and NMR
methods.1–11,19–24 For Schiff bases of simple aldehydes such
as salicylaldehyde, the imine form is the only observed
form.6,9 However, most of the Schiff bases show tautomerism
(Scheme 1). For the so-called proton transfer (enamine) form
much discussion has concerned the actual form.25 Two
resonance forms are given in Scheme 1. In the results section
only one form is shown for simplicity. So far, no compounds
of this type have been found to be fully in the enamine
form at ambient temperature, although compounds such
as 6-nitro-2-hydroxynaphtaldehyde are shifted very much
towards the enamine form.7 However, recent reports for
Schiff bases of gossypol indicate that some of these are in the
enamine form,12,26,27 although an earlier report disagrees.28
Furthermore, solvent may play a crucial role.
RESULTS
The Schiff bases of gossypol (1–4; see Scheme 2) have
been prepared using gossypol acetic acid and the amines
benzylamine, methylamine hydrochloride, methylamine 15
hydrochloride, 4-aminoacetophenone and 4-fluoroaniline.
N
The reaction with benzylamine is almost finished after 1 h
whereas 4-aminoacetophenone reacted much more slowly.
The reaction mixture of the latter after 1 h consisted of
gossypol, a Schiff base reacted at one of the aldehyde groups
and a Schiff base reacted at both aldehyde groups.
1
The H NMR data are given in Table 1. Resonances of
three XH protons are observed. The NH chemical shifts fall
into two groups, that of 1 and 2 and that of 3 and 4. In the
former case the NH proton chemical shift is close to 13.5 ppm,
the OH-6 proton shift is at ¾8 ppm and the OH-1 proton shift
Schiff bases of gossypol have shown interesting biological
properties.13–17 and thus knowledge about their tautomerism
is essential. The present work describes the synthesis and
NMR spectroscopic properties of Schiff bases of gossypol
with aliphatic and aromatic amines of varying base strength.
The 1H and 13C NMR chemical shifts, 3J(HC,NH) and
1
is at 5.6 ppm. In the latter group the NH H chemical shift
is close to 15.0 ppm and the two OH resonances are again
at 8 and 5.6 ppm. For the NH proton no great variation in
position is found by a change of temperature. However, the
OH-1 proton is shifted considerably to high frequency when
the spectrum is recorded in THF-d8 (Table 2).
ŁCorrespondence to: Poul Erik Hansen, Department of Life
Sciences and Chemistry, Roskilde University, PO Box 260, DK-4000
Roskilde, Denmark. E-mail: poulerik@ruc.dk
The 3J(HC,NH) coupling constant in all cases is close
°
to 12 Hz. Cooling of the sample to ꢀ25 C gave almost no
Contract/grant sponsor: Danish Natural Science Research Council.
change in this coupling constant. For 1 and 2 the coupling
Copyright  2005 John Wiley & Sons, Ltd.

Schiff bases of gossypol 303
Scheme 1. Tautomeric equilibrium and resonance forms.
in density functional theory (DFT) using B3LYP30,31 and a
6-31GŁ basis set. Chemical shifts were calculated using the
GIAO approach.32,33
Structures and NMR chemical shifts have been calculated
for the three derivatives: 1aOH, 2a, 2aOH; and 2b, 3aOH, 4a
(see Scheme 2). Calculations for all four molecules show that
the enamine form has the lowest energy in the gas phase.
The energy differences between the enamine and imine form
are: 27.1 kJ, for 1aOH, 25.4 kJ for 2a, 26.8 kJ for 2aOH, 24.7 kJ
for 2b and 23.6 kJ for 4a.
under non-exchanging conditions is 12.6 Hz and for 3 and
1
4 it is 11.7 Hz. For the 15N-enriched compound 2, a J(N,H)
coupling constant of 88.7 Hz could be obtained at ambient
temperature in THF-d8, together with 3JꢀCH,NHꢁ D 12.3 Hz,
3JꢀCH3, NHꢁ D 5.2 Hz and 2JꢀCH3,15 Nꢁ D 4.2 Hz.
Deuterium isotope effects on 13C chemical shifts have
been measured in 1 in CDCl3 and in THF-d8 at ambient
temperature. The isotope effects are given in Scheme 3. At
ambient temperature only one isotope effect is observed,
°
namely that of C-11. In CDCl3 at ꢀ25 C effects are also seen
at C-7 (ꢀ0.19 ppm), C-8 (0.09 ppm), C-1 (0.10 ppm), C-16
(0.19 ppm) and C-6 (broadening). The effects at C-1 and C-6
are believed to originate from deuteration of the C-1 and C-6
OH groups, respectively. This is supported by the finding
that both of the corresponding OH resonances are sharp
at low temperature. The OH-1 resonance was the sharpest.
For 1 in THF-d8 at ambient temperature, deuterium isotope
effects were found at C-7, C-8, C-11 and C-16 but not at C-6
Aplotofcalculated13C nuclearshieldingsforthe enamine
form of 1aOH vs. observed chemical shifts for 1 in CDCl3 is
shown in Fig. 1. A similar plot can be obtained for data of 3a
vs. 3 or 4a vs. 4. In the correlations, data points for C-2 have
been left out to compensate for the fact that the calculated and
measured compounds are not fully identical. The correlation
coefficients of 0.999 are very good. It is also seen that no major
differences exist whether the model used is of type a,b or aOH
(see Scheme 2). The calculated nuclear shieldings are very
similar from compound to compound, as are the chemical
shift (nuclear shielding) differences (Table 3). These data also
reveal quite large differences between carbon resonances
of enamine and imine forms, so that these forms can be
distinguished easily by 13C NMR. The fact that there is a large
difference in chemical shifts means that for an equilibrium a
change of temperature or deuterium substitution7,11 would
give rise to a large change. This is not found experimentally.
°
or C-1, but at ꢀ25 C both C-1 and C-8 show distinct isotope
effects (not shown in Scheme 3) and C-6 shows a broadening
°
just as in CDCl3, whereas at ꢀ55 C all six carbon resonances
C-1, C-6, C-7, C-8, C-11 and C-16 show well-resolved isotope
effects. In addition, an extra splitting is observed at the C-7
carbon resonance (see Scheme 3).
Theoretical calculations
The molecular geometries were optimized using the
Gaussian 98 suite of programs.29 The calculations are done
Copyright  2005 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2005; 43: 302–308

304
Q. T. That, K. P. P. Nguyen and P. E. Hansen
Scheme 3. Deuterium isotope effects on 13C chemical shifts
of 1 in CDCl3. Values in parentheses are recorded in THF-d8.
Values that are underlined are at low temperature: for CDCl3, at
°
°
ꢀ25 C; for THF-d8, at ꢀ55 C.
a
3J(HC,NH) of 12.8 Hz point towards the enamine form
being dominant. The finding that neither isotope effects
nor coupling constants change with solvent or temperature
points towards the enamine being the only constituent. This
is also supported by the finding that the 13C chemical shifts
do not change very much with temperature and by the
finding that the majority of the 13C chemical shifts are
very similar in 1, 3 and 4 as well as in the butylamine
derivative of gossypol.13 The finding that the Schiff bases of
gossypol are exclusively in the enamine form irrespective
of the amine or solvent used make these Schiff bases a
unique model for extracting basic parameters for the enamine
form, parameters that have proved very difficult to extract
Scheme 2. Compounds 1–4.
The choice of model turned out to be revealing for
understanding the structure. Originally the second monomer
unit was replaced either by a CH3 group as in 2b or by a
phenyl group as in 2a This gave a structure with the OH
1
from other tautomeric Schiff bases. The J(N,H) of 88.6 Hz
group out of the ring plane and pointing towards C—Hald
,
is close to the value of 92.6 Hz found by Kurkovskaya.1
which resulted in poor prediction of the OH-1 and NH
chemical shifts. By introducing a 2-hydroxyphenyl ring as
the second ring a much better fit was achieved, showing that
OH-1 is almost in the ring plane and that the two aromatic
rings are almost perpendicular. The calculated 1H nuclear
shieldings are given in Table 3 and a plot vs. the observed
1H chemical shifts is given in Fig. 1(b).
The calculated structures of the derivatives show the
formation of a hydrogen bond between the NH proton
and the oxygen at position 6 (Table 4). The OH-6 proton is
pointing towards the O-7 oxygen.
1
More recently a J(N,H) coupling of 80 Hz has been found
by extrapolation in Schiff bases of nitro derivatives of 2-
hydroxyacetophenone.7
The deuterium isotope effects on chemical shifts indicate
rather strong hydrogen bonding of this enamine. The
2C-˛(ND) of 0.34 ppm is clearly larger than is found for
aliphatic keto-enamines.34 At ꢀ25 C compound 1 in both
°
CDCl3 and THF-d8 shows a well-resolved isotope effect at
C-1 most likely due to deuteriation at OH-1. Deuteriation
at OH-6 leads only to a broadening at this temperature,
showing that exchange with external hydrogens is still too
fast. This is also confirmed by the slight broadness of this
As seen in Table 4, the difference in bond lengths is
moderate between 2a and 2aOH. Furthermore, the N-methyl
derivative (2) can be used as a model for an N-benzyl
derivative ( 1).
°
OH proton resonance. At ꢀ55 C in THF-d8 C-6 shows a well-
resolved splitting. At the same time C-7 shows an additional
splitting that can be ascribed to the presence of a hydrogen
bond from OH-6 to O-7. Deuteriation at OH-6 will give
rise to a small isotope effect, as is seen for intramolecular
hydrogen-bonded systems.35
DISCUSSION
The Schiff bases may exist as a tautomeric mixture as seen
in Scheme 1. However, the observation of a large positive
The reason why Schiff bases of gossypol are exclusively in
the enamine form (PT form) compared with numerous other
1
deuterium isotope effect at C-11, a J(N,H) of 88.6 Hz and
Copyright  2005 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2005; 43: 302–308

Schiff bases of gossypol 305
Table 1. The 13C chemical shifts of compounds 1, 3 and 4a
1
1
1
1
3
4
4
Butylb
(CDCl3 25 C) (CDCl3 ꢀ25 C) (THF-d8 25 C) (THF-d8 ꢀ25 C) (THF-d8 25 C) (CDCl3 25 C) (THF-d8 25 C) (CDCl3)
°
°
°
°
°
°
°
C-1
C-2
C-3
C-4
C-5
C-6
C-7
C-8
149.0
114.6
132.0
118.8
127.4
147.1
173.1
103.4
115.8
128.2
163.0
20.1
27.4
20.3
20.3
136.2
129.1
149.0
114.4
132.1
118.0
128.8
147.0
172.6
103.4
115.7
129.1
163.1
20.2
27.3
20.2
20.2
136.1
129.1
151.1
116.5
132.8
119.0
129.7
148.0
174.3
104.9
118.1
128.7
164.0
20.9
28.4
20.8
20.5
138.9
129.7
151.3
116.4
132.7
119.2
129.1
148.0
174.0
104.8
117.6 (broad)
128.6
164.1
20.7
152.0
113.7
134.6
120.2
131.3d
147.9
177.0
107.8
118.9
130.3d
153.4
20.5
n.o
20.5
20.5
135.2
131.2
149.5
114.5
133.0
120.0
129.1
147.2
174.5
105.3
116.4
130.0
154.7
20.5
151.5
115.9
133.9
118.5
129.3
147.8
175.4
106.7
119.6
130.1
155.2
20.4
148.9
115.7
131.7
118.1
127.1
147.2
172.1
103.0
114.7
128.9
162.9
20.0
C-9
C-10
C-11
C-12c
C-13
C-14c
C-15c
C-10
C-20
28.4
20.7
20.7
139.0
129.7
27.8
20.5
20.4
28.4
20.7
20.6
27.4
20.3
20.4
50.5
136.1
120.08e
119.98
117.16e
116.85
162.46e
159.20
—
137.6
120.65e
120.54
117.55e
117.24
163.09e
159.85
—
32.5
C-30
C-40
C-16
127.4
—
127.4
127.5
54.6
128.7
127.5
54.8
128.2
127.3
54.6
118.2
144.9
30.8
19.7
13.5
—
54.5
a The 13C NMR spectrum of compound 2 could not be recorded because of the low solubility.
b Taken from Ref. 13.
c Assignments may be interchanged.
d Assignment tentative.
e Splittings are due to C–F couplings.
Schiff bases of o-hydroxy aromatic aldehydes and ketones
is not immediately obvious. One contributing factor could
be the hydrogen bond formed between the OH group at
C-6 and the oxygen function at C-7, although the OH-6
chemical shift of ¾8 ppm is not signalling a very strong
hydrogen bond. However, the fact that the frequency of
OH-6 is shifted by >2 ppm compared with gossypol itself
indicates that the hydrogen bonding has been strengthened.
Furthermore, at low temperature, when exchange is slowed
down sufficiently, the hydrogen bond is recognized by
means of an isotope effect at C-7 (see previously). The steric
interaction formed by H-11, C-11, C-8, C-9, C-1 and O-1 is
clearly pushing the NH bond versus O-7, thereby causing a
favourable hydrogen bond. The N—O distance is calculated
The chemical shift of C-7 points to the C7—O bond
having considerable double bond character, as does the
calculated C7—O bond length (Table 4). The enamine
function is probably resonance assisted36 (see also Scheme 1)
but only to a minor degree. The present enamine definitely
can be seen as different to that of the 3-nitro-5-chloro-2-
hydroxyacetophenone, in which the C NH group has a
more positive charge.
EXPERIMENTAL
Compounds
šGossypol
(1,10,6,60,7,70-hexahydroxy-3,30-dimethyl-5,50-
diisopropyl[2,20-binaphthalene]-8,80-dicarboxaldehyde)
acetic acid was reacted with methylamine hydrochloride,
methylamine 15N hydrochloride, 4-aminoacetophenone,
benzylamine and 4-fluoroaniline in the two solvents chlo-
roform and ethanol. With methylamine hydrochloride and
methylamine 15N hydrochloride, ethanol was used; with
4-aminoacetophenone both ethanol and chloroform were
used, whereas with benzylamine and 4-fluoroaniline only
chloroform was used. All reactions were performed at
ambient temperature. The pH of the reaction mixtures
was adjusted to ¾5–7 by adding sodium hydroxide in
ethanol to methylamine hydrochloride and methylamine
˚
as ¾2.58 A (Table 4). The NH chemical shift of ¾13.5 ppm for
1 and 2 points towards a medium-strength hydrogen bond.
The increase in chemical shift to 15.0 ppm for 3 and 4 can
be ascribed partly to a slightly stronger hydrogen bond and
partly to ring current effects.
The OH-1 protons of the gossypol Schiff bases cannot
simultaneously form hydrogen bonds. Model calculations
using 2aOH show that the OH group is in the ring plane but
not hydrogen bonded. Such a picture is also in line with the
distinct solvent dependence of the OH-1 proton resonance, a
feature not seen for the other XH resonances.
Copyright  2005 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2005; 43: 302–308

306
Q. T. That, K. P. P. Nguyen and P. E. Hansen
Table 2. The 1H chemical shifts of compounds 1–4a
1
1
2
2
3
3
4
4
(CDCl3)
(THF-d8)b
(CDCl3)
(THF-d8)b
(CDCl3)
(THF-d8)b
(CDCl3)
(THF-d8)b
NH
13.59
9.74
13.74
(13.76)
[13.85]
9.89
(9.96)
[10.07]
8.25
(8.38)
[8.57]
7.52
(7.54)
[7.63]
7.30
(7.32)
[7.81]
3.72
(3.71)
[3.78]
4.71
(4.75)
[4.86]
2.01
(2.01)
[2.08]
1.49
13.24
(13.26)
13.30
9.78
8.25
7.52
7.10
Overlap
3.27d
2.02
1.50
1.48
—
14.85
10.16
7.8
15.01
10.43
8.21
7.60
7.25e
3.75
—
15.00
10.08
7.84
7.63
5.73
3.73
—
15.12
10.35
8.21
7.60
7.48
3.77
—
CHaldehyde
OH-6
CHarom
OH-1
CH
9.62
(9.68)
7.94
7.98
(8.01)
7.59
7.59
(7.61)
7.64
5.61
5.58
(5.64)
Not observed
3.72
3.72
3.72
(not observed)
CHxN
CH3Carom
CH3
4.65
3.30
(3.33)c
—
2.11
2.11
(2.12)
2.16
2.08
1.54
1.51
7.99
7.41
2.15
1.55
1.54
7.25
7.06
2.08
1.54
1.51
7.37
7.15
1.52
1.55
(1.54)
1.56
(1.50)
[1.54]
1.47
CH3
1.51
1.52
(1.53)
1.54
(1.49)
[1.58]
¾7.3
H-20
¾7.27
¾7.27
—
—
7.91
(¾7.3)
[¾7.4]
¾7.3
H-30
—
7.34
(¾7.3]
[¾7.4]
a
°
°
Values in parentheses are recorded at ꢀ25 C and values in square brackets at ꢀ55 C.
b For THF-d8 the CH2 resonance at 3.58 ppm was used as reference. No temperature compensation is included.
c
°
Showed a splitting of 5.1 Hz at ꢀ25 C.
d The 15N-enriched compound showed a splitting of 4.2 Hz.
e Assignment uncertain.
15N hydrochloride and by the addition of acetic acid to
4-aminoacetophenone, benzylamine and 4-fluoroaniline. The
crude products were purified by thin-layer chromatography
(TLC) with the eluent system chloroform–methanol–hexane
(8 : 1 : 1) or chloroform–acetone–hexane (8 : 1 : 1). The former
was used for products between gossypol and methylamine
hydrochloride or methylamine 15N hydrochloride, whereas
the latter was used for products between gossypol and
4-aminoacetophenone, benzylamine or 4-fluoroaniline.
solutions using a Varian Mercury 300 spectrometer. Other
solvents such as CD2Cl2 and tetrahydrofuran-d8 were also
1
used, the former at low temperature. The H NMR spectra
were recorded at 300 MHz with an acquisition time of 4.29 s
and the 13C spectra at 75.46 MHz with an acquisition time of
1.6 s. Tetramethylsilane (TMS) was used as internalreference.
The HMQC spectrum was recorded with an acquisition
time of 0.2 s, a spectral width of 7000 Hz, 2048 points in the 1H
dimension and 30 kHz spectral width in the 13C dimension;
512 increments and, aiming at a long-range coupling constant
of 7.5 Hz, 288 transients were recorded for each increment,
with a relaxation delay of 1.7 s.
NMR
The 1H and 13C NMR spectra of samples of non-deuterated
and deuterated compounds were measured in CDCl3
Copyright  2005 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2005; 43: 302–308

Schiff bases of gossypol 307
˚
Table 4. Calculated (B3LYP DFT) bond lengths (in A)
16
14
12
10
8
Bond
1aOH
2a
2aOH
3aOH
y = -1,1407x + 36,428
R2 = 0,9891
C1—C2
C2—C3
C3—C4
C4—C4a
C4a—C5
C5—C6
C6—C7
C7—C8
C8—C8a
C4a—C8a
C8—C11
C3—C12
C5—C13
C11—N
N—Cl6
Cl—O
1.404
1.413
1.385
1.413
1.464
1.367
1.458
1.439
1.468
1.436
1.406
1.512
1.529
1.330
1.455
1.374
1.356
1.272
0.975
0.988
1.030
1.081
1.092
2.582
1.397
1.412
1.389
1.411
1.465
1.369
1.458
1.442
1.467
1.430
1.401
1.512
1.528
1.333
1.450
1.385
1.389
1.270
0.972
0.986
1.029
1.086
1.083
2.608
1.403
1.413
1.385
1.414
1.463
1.367
1.146
1.437
1.468
1.437
1.408
1.512
1.530
1.328
1.449
1.374
1.356
1.274
0.975
0.988
1.030
1.081
1.082
1.575
1.402
1.407
1.386
1.411
1.466
1.366
1.455
1.447
1.471
1.435
1.397
1.510
1.529
1.345
1.398
1.376
1.358
1.270
0.974
0.987
1.031
1.077
1.082
2.579
6
4
2
0
15
20
25
30
35
(a)
1H Calculated nuclear shieldings
180
160
140
120
100
80
C6—O
C7—O
O1—H
O6—H
N—H
C11—H
C4—H
60
40
y = -0,946x + 187,65
R2 = 0,9987
20
0
N—O7
0
50
100
150
200
(b)
13C Calculated nuclear shieldings
Assignments
Figure 1. Plot of calculated 13C nuclear shieldings of
The assignment of 1 in CDCl3 at ambient temperature is
done based on a HMBC spectrum showing the following
cross-peaks, all values in ppm: 9.74, Hald (54.5, CH2; 173.1,
C-˛ (one-bond); 7.52, H-4 (114.6, C-2; 118.8, C-4 (one-bond);
¾7.27, H-20, H-30, H-40 (129.1, 127.4 and 127.5, not resolved);
4.65, CH2 (129.1, C-20; 136.2, C-10; 173.1, C-˛); 3.72, CH (127.4,
C-5; 128.2, C-10; 147.1, C-6); 2.11, CH3 (20.1, CH3(12) (one-
bond); 114.6, C-2; 118.8, C-4; 132.0, C-3); ꢀCH3ꢁ2, 20.3 (20.3,
ꢀCH3ꢁ2 (one-bond); 27.4, CH; 128.2, C-5). These peaks lead to
an unambiguous assignment. The assignment of compounds
2, 3 and 4 is done by analogy because the chemical shifts are
very similar and the compounds are too insoluble for HMBC
analysis. The assignments are confirmed by comparison
with the butylamine Schiff base of gossypol.13 For C-˛
the assignment is assured by observation of the variation
in chemical shift as a function of the substituent at N,
something that is not found to any large degree for the
remaining carbons. For compound 4 the assignment of the
carbon resonances of the extra benzene ring can be done
based on C–F coupling constants. The assignments reached
are very similar to those of the butylamine derivative of
Ref. 13.
compound 1aOH vs. measured chemical shifts of 1 (in CDCl3).
Table 3. The 13C and 1H calculated nuclear shielding
differences.a
1aOH
13C
2a
13C
2aOH
13C
2b
13C
4a
13C
1aOH
1H
C-1
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
ꢀ1.7
0.6
ꢀ0.2
1.2
ꢀ2.7
3.3
18.1
ꢀ4.0
ꢀ0.3
1.0
ꢀ0.4
ꢀ1.8
0.7
ꢀ0.3
0.7
ꢀ2.2
3.3
18.0
ꢀ4.0
ꢀ0.3
0.9
0.2 ꢀ0.1 Harom
ꢀ0.20
0.25
0
0.3 CH3C-3 ꢀ0.05
ꢀ0.3
0.9
ꢀ2.0
3.3
20.2
ꢀ3.2
ꢀ1.2
0.5
ꢀ0.8
0.7
0.1 Hald
1.1 OH-1
ꢀ0.26
ꢀ2.14
1.31
ꢀ3.91
ꢀ0.72
ꢀ0.06
ꢀ0.06
ꢀ0.29
ꢀ1.8 ꢀ2.2 OH-6
3.3
20.1
3.3 NH
21.8 CH
ꢀ3.0 ꢀ2.3 CH3C
ꢀ1.5 ꢀ1.6 CH3C
0.2
0.8 CH2
C-11 ꢀ11.1 ꢀ11.8
ꢀ9.7 ꢀ12.2 ꢀ16.8
C-12 ꢀ0.2
C-13 ꢀ0.6
C-14 ꢀ0.3
C-15 ꢀ0.1
ꢀ0.2
ꢀ0.7
ꢀ0.2
ꢀ0.2
ꢀ0.3
ꢀ0.6
ꢀ0.3
0.3
0
ꢀ0.2
ꢀ0.7 ꢀ0.7
ꢀ0.5 ꢀ0.5
ꢀ0.2 ꢀ0.1
Acknowledgements
The authors wish to thank the Danish Natural Science Research
Council for support to our hydrogen bond research and Rita Buch
for helping to record the NMR spectra.
C-16 ꢀ8.1 ꢀ10.3
ꢀ9.4 ꢀ10.3
—
a Nuclear shielding of imine—enamine. Nuclear shieldings can
be converted to chemical shifts by plotting chemical shift vs.
nuclear shielding (see Fig. 1).
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