Investigation of two- and three-bond carbon–hydrogen coupling constants in cinnamic acid based compounds

Article abstract of DOI:10.1002/mrc.4469

Two- and three-bond coupling constants (²J_HC and ³J_HC) were determined for a series of 12 substituted cinnamic acids using a selective 2D inphase/antiphase (IPAP)-single quantum multiple bond correlation (HSQMBC) and 1D proton coupled ¹³C NMR experiments. The coupling constants from two methods were compared and found to give very similar values. The results showed coupling constant values ranging from 1.7 to 9.7 Hz and 1.0 to 9.6 Hz for the IPAP-HSQMBC and the direct ¹³C NMR experiments, respectively. The experimental values of the coupling constants were compared with discrete density functional theory (DFT) calculated values and were found to be in good agreement for the ³J_HC. However, the DFT method under estimated the ²J_HC coupling constants. Knowing the limitations of the measurement and calculation of these multibond coupling constants will add confidence to the assignment of conformation or stereochemical aspects of complex molecules like natural products. Copyright

Full text of DOI:10.1002/mrc.4469

Research article
Received: 11 April 2016
Revised: 31 May 2016
Accepted: 1 June 2016
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/mrc.4469
Investigation of two- and three-bond carbon–
hydrogen coupling constants in cinnamic acid
based compounds
Gregory K. Pierens,* Taracad K. Venkatachalam and David C. Reutens
2
3
ABSTRACT Two- and three-bond coupling constants ( JHC and JHC) were determined for a series of 12 substituted cinnamic acids using
13
a selective 2D inphase/antiphase (IPAP)-single quantum multiple bond correlation (HSQMBC) and 1D proton coupled C NMR exper-
iments. The coupling constants from two methods were compared and found to give very similar values. The results showed coupling
13
constant values ranging from 1.7 to 9.7 Hz and 1.0 to 9.6 Hz for the IPAP-HSQMBC and the direct C NMR experiments, respectively.
The experimental values of the coupling constants were compared with discrete density functional theory (DFT) calculated values and
3
2
were found to be in good agreement for the JHC. However, the DFT method under estimated the JHC coupling constants. Knowing the
limitations of the measurement and calculation of these multibond coupling constants will add confidence to the assignment of
conformation or stereochemical aspects of complex molecules like natural products. Copyright © 2016 John Wiley & Sons, Ltd.
2
3
Keywords: NMR; heteronuclear coupling constants; DFT; J ; JHC; cinnamic acid; IPAP-HSQMBC
HC
crystallography or total synthesis is difficult to achieve. In this regard,
Introduction
it would be very useful to compare the experimental and calculated
n
n
n
Long-range J and J coupling constants have played an impor-
JCH coupling constants to validate the structure of the molecule of
HH
CH
[26]
tant role in the structure elucidation of synthetic compounds and
natural products. The measurement of H– H coupling constants is
well defined either by direct measurement or simulation of the mul-
tiplet of interest, but there is no general method of measuring H– C
coupling constants. There are two general strategies employed today
for measuring the long-range heteronuclear coupling constants. The
interest. In a recent report by Kutateladze et al. in 2015 it was
shown that using a new basis set (DU8) and the NBO hybridization
parameters yielded excellent accuracy of 0.29 Hz (rmsd) for the cou-
pling constant with the maximum unassigned error not exceeding
1 Hz in a diverse collection of natural products. All calculated cou-
1
1
1
13
pling constants are reported in the Supporting Information (S3–14).
[1–4]
[10]
first is HSQC-TOCSY based pulse sequence strategies.
Although
We aim to use 1D (direct) and 2D selective NMR (IPAP-HSQMBC
)
these experiments are useful they are unsuitable for coupling
constants involving quaternary carbons. The second method either
experiments to measure the two- and three-carbon–hydrogen
coupling constants in 12 cinnamic acid-based compounds, to use
the recently described density functional theory (DFT) methods of
Kutateladze to calculate two- and three-carbon–hydrogen coupling
constants and to compare the calculated with the experimentally
measured coupling constant values. Consistency between measured
and calculated heteronuclear long-range coupling constants
enhances confidence in the reported structures for compounds.
[5]
[6]
uses long-range optimised HMBC or HSQMBC pulse sequences.
These methods are highly suited for measuring coupling constants
between non-protonated carbons but suffer from the problem of
time consuming post processing and antiphase multiplets. Other
[26]
[
7]
[8]
[9]
experiments like EXCIDE , HSQC-HECADE and J-HMBC , in which
the
n
JCH coupling evolves in the indirect dimension, have been
successfully applied but require long experimental time to achieve
[10–15]
the desired resolution. Recently, Parella et al.
used selective
HSQMBC experiments acquired in two different modes, inphase
and antiphase (IPAP), to extract the JCH coupling constants. The
Experimental
n
processing of the data involves two steps, in which the data are
Synthesis
added (IP+AP) and subtracted (IPÀ AP), and the corresponding
Synthesis of cinnamic acid ester derivatives was carried out using
n
rows from these 2D datasets are compared to extract the JCH
.
[27–31]
modified literature procedures.
In brief, the appropriately
Quantum mechanical calculations of NMR parameters such as
chemical shifts and coupling constants have become a very popular
tool for synthetic and natural product chemistry for the assignment
of stereochemistry within a molecule of interest. Calculation of
substituted cinnamic acid derivative, excess of the alcohol (metha-
[16–25]
* Correspondence to: Gregory K. Pierens, Centre for Advanced Imaging, The
University of Queensland, St Lucia, Brisbane 4072, Australia. E-mail: g.
pierens@uq.edu.au
NMR chemical shifts has been reviewed extensively.
These
calculations have also been used for the reassignment of structures
in complex molecules, such as natural products, in which validation
of the proposed structure by gold standard methods like X-ray
Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia
Magn. Reson. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.

G. K. PIERENS, T. K. VENKATACHALAM AND D. C. REUTENS
nol, ethanol or isopropanol) and HCl (10M) were heated at reflux
for 8 h. The solvent was evaporated, and the residue was treated
with ice cold aqueous sodium hydroxide, and the undissolved ma-
terial was extracted with ethyl acetate. The organic layer was
washed twice with aqueous sodium hydroxide followed by brine
and finally dried over anhydrous sodium sulfate. Filtration and
evaporation of the solvent gave the desired esters. The esters were
either solid and or viscous liquids. The compounds were checked
using routine analytical techniques to confirm the structure of the
compounds. Each of the samples was subjected to complete
conformations were further optimised, and Natural Bond Orbital
(NBO), chemical shift and coupling constants calculated in
[
33]
Gaussian
(see Supporting Information for an example of the
Gaussian script for acetic acid (S2)).
n
The JHC coupling constants were calculated using the method of
[
34]
Kutateladze and Mukhina. The data were pre-processed using
the Python script supplied from Kutateladze web site, and the
resulting file was up loaded to Kutateladze web site for processing
(http://kgroup.du.edu/nmr).
1
13
NMR structure verification using H, C, COSY, HSQC and HMBC.
Results and Discussion
In the present study a set of 12 compounds consisting of substituted
cinnamic acids and ester derivatives was synthesised using a modifi-
cation of a previously described procedure (see Experimental sec-
tion). The cinnamic acid skeleton was functionalized at two sites.
The aromatic moiety in the structure was functionalized in the
para-position with electron donating and withdrawing groups. This
was done to examine the effect of functional groups electronic influ-
ence on the coupling constants associated with protons and carbons
in the structure. Additionally, the carboxylic acid moiety was esteri-
fied with three different alkyl groups. The three different group were
used to evaluate any steric bulk influence on the magnitude of ex-
perimentally determined coupling constants. Table 1 shows the
structure of the 12 derivatives prepared in the present study.
NMR Spectroscopy
6
All cinnamic acid derivatives were dissolved in DMSO-d . NMR exper-
iments were recorded on a BRUKER 700 Avance III HD with a three-
channel 5-mm TCI cryoprobe incorporating a z-gradient coil. All data
were acquired and processed with TOPSPIN v3.2. The NMR samples
6
contained approximately 50–100 mg dissolved in 600 μl DMSO-d .
1
3
The C NMR data were acquired using the Bruker pulse se-
quence ‘zgpg’ experiment with a 60° pulse and with proton
decoupling turned off (0 watts). The number of points acquired
was 128 k and the sweep width was 80 or 228ppm.
1
13
All H– C IP- and AP-HSQMBC experiments were separately
[10]
recorded. The recycle delay was set to 1 s, number of scans set
n
1
to 4 and the interpulse Δ delay (=1/4 JCH) was set using 8 Hz. The
Initially, the J coupling constants were measured directly on a
1
13
selective 180 pulse was Gaus1_180r.1000 of length 20 ms. The
sweep width was 5 ppm centred on the chemical shift of interest.
There were 4096 and 128 points acquired in F2 and F1, respectively.
Total acquisition time for each experiment was 15 min. IP and AP
data were added/subtracted in the time-domain. Prior to Fourier
transformation of each data set, zero filling to 8192 points in F2
subset of compounds (3, 6, 8 and 11) via a H coupled C NMR
1
Table 2. JCH coupling constants for compounds 3, 6, 8 and 11 and the
numbering scheme used
(digital resolution of 0.43 Hz), 1024 points in F1 and a sine squared
function in both dimensions were applied. The corresponding rows
from the addition and subtraction dataset were compared, and the
coupling constant was extracted from the multiplet offset.
1
Position
Compounds, JCH
3
6
8
11
Computational Calculation (DFT)
2
162.6
159.2
165.5
169.6
—
164.4
159.5
165.8
169.4
—
162.1
154.9
159.5
160.9
144.3
147.4
126.7
161.9
154.9
159.5
160.6
144.9
148.1
126.4
Monte Carlo Conformational searching was performed using
3
[
32]
Macromodel (Schrodinger Inc) for all compounds. Torsional sam-
pling (MCMM) was performed with 1000 steps per rotatable bond.
Each step was minimised with the OPLS-2005 force field using the
Truncated Newton Conjugate Gradient (TNCG) method with maxi-
mum iterations set at 50 000 and energy convergence threshold
at 0.02. All other parameters were default values. The resulting
number of unique conformations are shown in Table 1. All
5,5′
6,6′
8
9
—
147.4
—
10
—
—
: not in compound.
Table 1. The structural features of 12 cinnamic acid derivatives used in the present study and the number of conformers used in the DFT calculations
Compound
1
2
3
4
5
6
7
8
9
10
11
12
R
R
#
1
H
H
2
H
OMe
4
H
Me
H
Me
OMe
4
Me
Et
H
4
Et
OMe
8
Et
i-Pr
H
i-Pr
OMe
4
i-Pr
2
NO
2
2
NO
2
2
NO
4
2
NO
2
2
of conformers
2
2
wileyonlinelibrary.com/journal/mrc
Copyright © 2016 John Wiley & Sons, Ltd.
Magn. Reson. Chem. (2016)

Investigation of two- and three-bond carbon–hydrogen coupling constants in cinnamic acid based compounds
experiment, and the results are shown in Table 2. The numbering of
the protons/carbons associated with the structure are also shown in
Table 2. On examination of the coupling constants, it was observed
The coupling constants are shown in Table 3. As can be seen there
is very little difference between the corresponding coupling con-
2
3
stants for the similar JHC or JHC in these compounds. One of the
1
3
that the J coupling constants were consistent for C3 in the com-
largest differences is for the JH9C1 in the methyl, ethyl and isopro-
pounds with the same aromatic moieties, i.e. the nitro compounds
pyl esters, where the methyl ester had the largest coupling of
3.88 Hz and the isopropyl ester had the smallest coupling with
2.97 Hz. The JH6/6′C7 also showed a significant difference. This is un-
derstandable because this carbon has either a nitro (3 and 6) or
methoxy (8 and 11) group attached at the 4-position of the aro-
matic ring which seems to result in a ~0.8-Hz reduction in coupling
constant going from a nitro to methoxy moiety. This result is
(3 and 6) having a larger coupling of ~159 Hz compared to the
2
methoxy compound (8 and 11) of ~155 Hz. From these results, it
was evident that the functionalisation of the acid moiety with differ-
ent ester groups does not significantly change the coupling con-
stant for C3. This trend is also seen for C5/5′ and C6/6′, with the
nitro substituted compounds (3 and 6) having a 6 and 8-Hz change
from the methoxy compounds (8 and 11), respectively. Based on
the results we may conclude that the nature of the substitution at
the 4-position of the phenyl ring does affect the magnitude of ob-
served coupling constant values. For C2, it appears that the free
2
3
Table 3. Subset of JCH and JCH coupling constants measured from the
proton-coupled carbon spectra for compounds 3, 6, 8 and 11
1
acid, ethyl and isopropyl esters seem to give the same J coupling
n
J
HC
Compounds
constant of 161.9–162.6 Hz, but the methyl ester approximately
2
Hz higher coupling constant of 164.4 Hz.
3
6
8
11
Interestingly, on further examination of these spectra, the major-
H2–C1
2.55
1.34
5.41
6.78
3.11
2.08
5.09
4.44
2.38
1.56
5.48
6.91
3.27
2.01
5.03
4.48
2.47
1.09
5.58
6.84
3.00
2.22
5.00
4.49
2.40
1.11
5.58
6.82
3.12
2.33
5.26
4.50
ity of the carbon resonances were more complex than first ex-
2
3
H2–C3
pected. Direct extraction of JCH and JCH coupling constants was
possible. Proton-coupled carbon NMR experiments were used reg-
ularly in the early years of NMR to assign the number of protons di-
rectly attached to carbon atoms i.e. C (s), CH (d), CH (t) and CH (q),
H2–C4
H3–C1
H3–C2
2
3
[35]
H3–C4
whereas DEPT or edited HSQC is now used almost exclusively.
An example of these couplings can be seen in Fig. 1 in which the
carbonyl carbon (C1) shows the expected increase in complexity
as the number of coupling partners increases. This data can be used
H3–C5
H5/5′–C3
H5/5′–C4
H5/5′–C7
H5–C5′
H6/6′–C4
H6/6′–C7
H6–C5
≤0.7
≤0.7
≤0.7
≤0.7
2
3
9.59
6.92
7.78
3.42
9.61
7.01
7.77
3.43
9.26
7.39
7.26
2.61
9.32
7.37
7.29
2.78
to extract the J and J coupling constants when large amounts
CH
CH
of material are available because of the low sensitivity of acquiring
13
C NMR.
The four compounds (3, 6, 8 and 11) were used as a test subset
to extract the long-range coupling constants from the proton-
≤0.7
≤0.7
≤0.7
≤0.7
1
3
H8–C7
NA
NA
NA
NA
NA
NA
3.88
NA
NA
NA
4.16
3.13
2.63
4.42
NA
4.23
2.97
1.61
4.24
4.71
coupled C spectrum. Many of the first-order multiplets were used;
however, C6/6′ were not used to extract any coupling information
because of the second-order appearance of the multiplet. Interest-
ingly, the C5/5′ multiplet could be used for extracting coupling con-
stants. The DAISY programme (V3, 2014) within Topspin (V3.5 pl2)
was used to extract the couplings and chemical shifts by simulation.
H9–C1
H9–C10
H10–C9
H10′–C10
Figure 1. The carbonyl carbon (C1) from a proton coupled NMR experiment for four different compounds resulting in different multiplicity (3, 6, 8 and 11).
Magn. Reson. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

G. K. PIERENS, T. K. VENKATACHALAM AND D. C. REUTENS
1
n
consistent with the data observed for J coupling constants
discussed earlier). There is also a difference in the magnitude of
The IPAP-HSQMBC sequence was used to measure the JHC
(
coupling constants in all 12 compounds used in this study. This
pulse sequence relies on selective excitation of a multiplet. Many
of the proton multiplets were used but, when overlapping signals
occurred in the spectrum, the measurement became very
complicated and sometimes impossible to interpret. The
chemical shifts that were measured without ambiguity are shown
2
the coupling constant observed between JH9C10 in the ethyl and
isopropyl esters. The ethyl had a value of 2.63Hz while this de-
ceased to 1.61 Hz for the isopropyl ester. Therefore, we can see
there is a small difference because of the change in structure. From
now on, we will use the coupling constants listed in Table 3 as the
3
2
‘
gold standard’ or absolutely correct values for the following com-
in Tables 4 and 5 for the JHC and JHC coupling constants, re-
spectively. Because the JHC and JHC coupling constants have
2
3
parisons and discussions.
One carbon the authors would like to highlight is C7, which is the
most complex of the multiplets examined (Fig. 2). In compounds 8
and 11 having the methoxy group at the para-position of the aro-
matic ring, C7 appears as a very complex multiplet despite having
only three coupling partners. In compounds 8 and 11 this carbon
is coupled to H5/5′, 6/6′ and the three methoxy protons (H8) which
results in the multiplicity of triplet of triplets of quartets (36 lines). By
comparison C7 in the nitro compounds (3 and 6) is a triplet of trip-
lets (9 lines). Figure 2 illustrates, both the experimentally and the
simulated multiplets obtained for C7 in compound 8.
been measured using two different experiments for the subset
of four compounds (3, 6, 8 and 11), the coupling constants from
13
the C and IPAP-HSQMBC methods were plotted against each
2
3
other for the JHC and JHC, and the graphs are shown in Fig. 3.
3
The JHC showed that the two methods are in very good agree-
ment with an average deviation of 0.1Hz and the largest devia-
tion between H2–C4 of 0.4Hz for compounds 8 and 11. Even
2
for the smaller
JHC coupling constants, both methods also
showed a good agreement, but a slightly lower correlation was
observed. The average deviation of 0.23Hz with the largest of
Figure 2. The experimental (proton coupled carbon spectrum) and simulated C7 multiplet of compound 8.
3
Table 4. Experimental J coupling constants measured by the IPAP-HSQMBC experiment and calculated by method of Kutateladze and Mukhina
(“du8c”in parenthesis) for compounds 1–12
Compounds
H2–C4
H3–C1
H3–C5/5′ H5/5′–C3 H5/5′–C5′/5 H5/5′–C7 H6/6′–C4 H6/6′–C6′/6
H8–C7
H9–C1
H10–C10
1
2
3
4
5
6
7
8
9
5.3 (5.3) 6.8 (7.1)
5.2 (5.2) 6.8 (7.0)
5.5 (5.6) 6.8 (7.2)
5.3 (5.3) 6.9 (7.0)
5.3 (5.3) 6.9 (6.9)
5.6 (5.6) 6.8 (7.1)
5.3 (5.3) 6.8 (6.9)
5.2 (5.3) 6.7 (6.8)
5.6 (5.6) 6.8 (7.0)
5.2 (5.3) 6.7 (6.9)
5.2 (5.3) 6.8 (6.8)
5.5 (5.6) 6.8 (7.0)
5.1 (5.6)
5.4 (5.7)
5.0 (5.7)
5.2 (5.6)
5.2 (5.7)
5.1 (5.6)
5.1 (5.6)
5.3 (5.7)
5.0 (5.6)
5.1 (5.7)
5.2 (5.7)
5.1 (5.7)
4.6 (5.1)
4.4 (4.7)
4.4 (4.9)
NA (5)
6.4 (6.5)
7.4 (7.3)
6.9 (7.1)
NA (6.5)
7.4 (7.3)
6.7 (7.1)
6.2 (6.5)
7.4 (7.3)
6.8 (7.1)
6.2 (6.6)
7.4 (7.3)
6.8 (7.1)
7.4 (7.5)
9.4 (9.3)
9.6 (9.5)
NA (7.5)
9.5 (9.3)
9.6 (9.5)
7.5 (7.5)
9.4 (9.3)
9.7 (9.5)
7.4 (7.5)
9.5 (9.3)
9.7 (9.5)
NA (7.5)
7.5 (7.3)
7.7 (7.9)
NA (7.4)
7.5 (7.3)
7.6 (7.9)
NA (7.4)
7.5 (7.3)
7.6 (7.9)
NA (7.4)
7.5 (7.3)
7.8 (7.9)
NA (7.6)
4.8 (4.6)
4.5 (4.6)
NA (7.6)
4.9 (4.6)
4.7 (4.6)
NA (7.5)
5.0 (4.7)
4.6 (4.6)
NA (7.6)
5.0 (4.7)
4.7 (4.6)
—
4.1 (4.1)
—
—
—
—
—
—
—
—
4.0 (4.1)
—
4.6 (4.7)
4.4 (4.9)
4.8 (5.0)
4.5 (4.7)
4.3 (4.8)
4.9 (5)
4.2 (4.0) 4.0 (4.1)
—
—
—
3.9 (4.2)
3.1 (3.0)
—
—
4.3 (4.0) 3.1 (3.1)
—
—
—
3.1 (3.1)
2.9 (3.1)
—
10
11
12
4.7 (4.4)
4.6 (4.4)
4.7 (4.3)
4.5 (4.7)
4.3 (4.8)
4.2 (4.0) 3.0 (3.2)
2.8 (3.1)
—
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Copyright © 2016 John Wiley & Sons, Ltd.
Magn. Reson. Chem. (2016)

Investigation of two- and three-bond carbon–hydrogen coupling constants in cinnamic acid based compounds
2
Table 5. J coupling constants measured by the IPAP-HSQMBC experiment and calculated by method of Kutateladze and Mukhina (in parenthesis) for
compounds 1–12
Compounds
H2–C1
H2–C3
H3–C2
H3–C4
H6/6′–C7
H9–C10
H10–C9
1
2
3
4
5
6
7
8
9
2.8 (1.8)
2.7 (1.8)
2.6 (1.6)
2.6 (1.4)
2.6 (1.3)
2.5 (1.2)
2.6 (1.4)
2.6 (1.3)
2.4 (1.2)
2.6 (1.4)
2.6 (1.3)
2.4 (1.2)
1.8 (1.6)
1.7 (1.3)
NA (1.9)
1.8 (1.5)
1.8 (1.3)
1.8 (1.8)
2.0 (1.5)
1.7 (1.2)
NA (1.7)
1.9 (1.4)
1.9 (1.2)
NA (1.7)
3.0 (3.7)
3.0 (3.7)
3.4 (4.0)
3.1 (3.9)
3.2 (3.8)
3.3 (4.1)
3.1 (3.9)
3.0 (3.8)
3.3 (4.1)
3.2 (3.9)
3.2 (3.8)
3.3 (4.1)
2.4 (1.7)
2.4 (1.7)
2.6 (1.9)
2.4 (1.8)
2.3 (1.8)
2.3 (2.0)
2.3 (1.8)
2.3 (1.8)
2.4 (2.1)
2.2 (1.9)
2.2 (1.8)
2.4 (2.1)
NA (1.3)
2.6 (2.2)
3.6 (3.3)
NA (1.3)
2.8 (2.2)
3.5 (3.3)
NA (1.3)
3 (2.2)
—
—
—
—
—
—
—
—
—
—
—
—
2.7 (2.3)
2.8 (2.3)
2.7 (2.4)
1.9 (1.6)
1.9 (1.6)
2.1 (1.6)
4.5 (3.7)
4.5 (3.7)
4.5 (3.7)
4.3 (3.7)
4.4 (3.7)
4.3 (3.7)
3.4 (3.3)
NA (1.3)
2.8 (2.2)
3.3 (3.3)
1
1
1
0
1
2
3
2
Figure 3. Comparison of the measured
JHC (a) and
J
HC (b) coupling
13
3
2
constants from the direct C and the IPAP-HSQMBC experiments for
compounds 3, 6, 8 and 11. ( JHC (36 coupling constants) and
Figure 4. Comparison of the measured and calculated JHC (a) and JHC
3
2
J
13
HC (23
(b) from the direct C and the du8c method for compounds 3, 6, 8 and
3
2
coupling constants)) The dotted line represents a 1:1 correspondence.
11. ( JHC (36 coupling constants) and JHC (23 coupling constants)) The
dotted line represents a 1:1 correspondence.
H2–C3 of 0.79Hz for compound 11. However we found the IPAP-
HSQMBC overestimated the JHC coupling values. This could be
2
13
correspondence between the C direct measurement and the cal-
because of two factors. First, digital resolution, which is lower in
the IPAP-HSQMBC experiment (~0.8Hz) compared to the direct
carbon (~0.3Hz), and second, during the processing of the
IPAP-HSQMBC experiment the datasets are added and
subtracted. This could lead to non-complete removal of the
culated data. The average deviation was 0.2Hz with a maximum of
2
0.7 for the H3–C5 coupling constant. But for the JHC calculated data
2
showed less correlation compared to the measured JHC coupling
constant, with an average deviation of 0.52Hz and a maximum of
2
1.18 Hz for the H2–C1 coupling. This larger deviation for the JHC
proton-proton couplings.
coupling constant could be directly a result of the smaller size of
the JHC coupling constant. Most of the DFT calculated coupling
constants were smaller than the experimental observed values.
n
2
The J coupling constants were calculated using the method of
HC
[
34]
Kutateladze and Mukhina.
From now on we will refer to this
method as ‘du8c’. The coupling constants (Tables 4 and 5) were
Thus we can see from this subset group of compounds that the
13
3
compared to the direct C method, and the results are shown in
JHC for the IPAP-HSQMBC and du8c compare well with the direct
3
13
Figs 4 and 5. The J data showed that there was a very good
HC
measurement of the coupling constants from the C NMR with
Magn. Reson. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/mrc

G. K. PIERENS, T. K. VENKATACHALAM AND D. C. REUTENS
2
were in good agreement with experimental values, but the J
HC
coupling constants were predicted to be smaller than the mea-
sured values. Comparison of the data from the 12 compounds
3
showed that the
JHC coupling constants from the calculated
method were slightly higher than the measured values from
the IPAP-HSQMBC method, which showed an average deviation
2
of 0.21 Hz. The calculated JHC coupling constants were consis-
tently lower than the measured values from the IPAP-HSQMBC
experiment. Our study demonstrates that long-range coupling
13
constants that can be obtained from the proton-coupled
C
NMR spectrum if the multiplet is well resolved and large amounts
of the compound are available.
Acknowledgements
This research was funded in part by the Australian Research Council
Linkage grant # LP130100703 (DR). This research was supported by
the Centre for Advanced Imaging, The University of Queensland
and the Queensland NMR network.
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HSQMBC experiment with the calculated values from du8c
[
[
[
[
showed a similar result as observed in the subset of the data.
The J showed that the measured and predicted coupling were
3
HC
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n
The
JHC coupling constants of 12 cinnamic acid based
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3
2
2011, 133, 6072.
HC
HC
13
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[
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Supporting information
3
2
The J and J coupling constants measured by IPAP-HSQMBC
HC
HC
compared very well with the couplings derived from the proton-
coupled C NMR data. The calculated JHC coupling constants
Additional supporting information may be found in the online ver-
sion of this article at the publisher’s web site.
1
3
3
wileyonlinelibrary.com/journal/mrc
Copyright © 2016 John Wiley & Sons, Ltd.
Magn. Reson. Chem. (2016)