H chemical shifts in NMR. Part 24? - Proton chemical shifts in some gem-difunctional compounds: 3-endo- and 3-exo-substituted norbornanones

Article abstract of DOI:10.1002/poc.1094

The complete assignment of the ¹H and ¹³C NMR chemical shifts, from 2D techniques and spectra recorded at 500 MHz, for 3-substituted norbornanones with Cl, Br, I, SMe and SeMe substituents at endo and exo positions and 3-exo-hydroxynorbornanone is reported. The observed ¹H chemical shifts are compared with the corresponding calculated values using the semi-empirical CHARGE method and ab initio calculations at the B3LYP/6-311++G(d,p) theory level. The molecular geometries were obtained through Density Functional Theory (DFT) methods. Good agreement between the experimental and both sets of calculated values is observed with the CHARGE calculations being more accurate for this series. This illustrates the utility of the CHARGE program for chemical shift assignments and also as a tool for the elucidation of chemical structures. Copyright

Full text of DOI:10.1002/poc.1094

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2006; 19: 376–383
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.1094
1H chemical shifts in NMR. Part 24y—proton chemical
shifts in some gem-difunctional compounds:
3-endo- and 3-exo-substituted norbornanones
2
2
3
Gisele F. Gauze,1 Ernani A. Basso,1 Mateus G. Campos, Roberto Rittner and Raymond J. Abraham
*
1
´
´
Chemistry Department, State University of Maringa, CEP-87020-900, Maringa, PR, Brazil
2Physical Organic Chemistry Laboratory, Chemistry Institute, State University of Campinas, Caixa 6154, 13084-971 Campinas, SP, Brazil
3Chemistry Department, The University of Liverpool, 147, Liverpool L69 3BX, UK
Received 17 November 2005; revised 15 March 2006; accepted 5 May 2006
1
ABSTRACT: The complete assignment of the H and 13C NMR chemical shifts, from 2D techniques and spectra
recorded at 500 MHz, for 3-substituted norbornanones with Cl, Br, I, SMe and SeMe substituents at endo and exo
1
positions and 3-exo-hydroxynorbornanone is reported. The observed H chemical shifts are compared with the
corresponding calculated values using the semi-empirical CHARGE method and ab initio calculations at the B3LYP/
6–311þþG(d,p) theory level. The molecular geometries were obtained through Density Functional Theory (DFT)
methods. Good agreement between the experimental and both sets of calculated values is observed with the CHARGE
calculations being more accurate for this series. This illustrates the utility of the CHARGE program for chemical shift
assignments and also as a tool for the elucidation of chemical structures. Copyright # 2006 John Wiley & Sons, Ltd.
1
KEYWORDS: H and 13C NMR; norbornanones; NMR calculations; GIAO; CHARGE
INTRODUCTION
different magnetic susceptibilities (xx, xy and xz ) along
the three principal axes. A number of investigations,
The influence of the carbonyl group on the chemical shifts
of neighbouring protons has been of interest since the
early days of NMR spectroscopy, the low-field chemical
shift of the aldehyde proton being a conspicuous example.
This was explained as due to the carbonyl anisotropy and
the standard description of this anisotropy due to
Jackman2 is one of the most well known illustrations
in NMR spectroscopy. The question of an appropriate
description of the carbonyl anisotropy has been recently
reviewed,1b but a brief account of the main related papers
is also given here.
Jackman2 had suggested that there is a large
diamagnetism in the direction normal to the nodal plane
of the p-orbitals, whereas Pople’s3 calculations indicated
a paramagnetism centred on the carbon atom, large in the
x direction and the largest diamagnetism on the O atom in
commencing with that of Zurcher,5 have used this
6
—
description of the C O anisotropy with the McConnell
—
equation together with the electric field effect of the C
—
—
O to explain the observed substituent-induced chemical
shifts (SCS) of the carbonyl group in ketones.7–11 More
recent analysis1b used the CHARGE program, which
includes the carbonyl anisotropy and electric field plus an
oxygen but not carbon steric term. Version CHARGE8c is
used in this study.
1
A general calculation of the H chemical shifts for
carbonyl compounds using the ab initio gauge indepen-
dent atomic orbital (GIAO) method has not been reported
to date, the basis set dependence of such calculations
being a severe problem. A recent investigation by
Lampert et al.12 for phenol and benzaldehyde derivatives
(15 compounds) led to deviations of ca. 0.5–1.0 ppm
depending on the procedure and basis set used and this
may well represent the limit of accuracy of such
calculations.
—
the z direction (i.e. along the C O bond). These and
—
other early investigations are well reviewed by Bothner-
By and Pople.4
The general carbonyl group (R1COR2) has no elements
of symmetry and therefore has, in principle, three
Most of the above investigations considered only
aliphatic ketones and they therefore obtained the
anisotropy for an isolated saturated carbonyl group.
However, the simultaneous presence of a carbonyl group
and a substituent attached to the same carbon results in
changes in the carbonyl electronic density, which has
been explained by the occurrence of orbital interactions.
´
*Correspondence to: E. A. Basso, Departamento de Quımica, Uni-
versidade Estadual de Maringa, bloco 22, secretaria, Av. Colombo
´
´
5790, CEP 87020-900, Maringa, PR, Brazil.
E-mail: eabasso@uem.br
yFor Part 23 see Ref. [1a]
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 376–383

1H CHEMICAL SHIFTS IN NMR
377
This has been illustrated by the anomalous substituent
THEORY
chemical shifts observed for several series of a-
substituted carbonyl compounds.13
Camphor derivatives are useful compounds for the
As the theory has been given previously1b,11,16 only a
brief summary of the latest version (CHARGE8c) will be
given here. The theory distinguishes between short-range
substituent effects over one, two and three bonds, which
are attributed to the electronic effects of the substituents,
and long-range effects due to the electric fields, steric
effects and anisotropy of the substituents.
1
study of H chemical shifts, because they have a rigid
geometry and all protons are non-equivalent and
reasonably well resolved in high-field NMR spectra.
1
The H NMR chemical shifts for the a-halocamphors,
from spectra at 600 MHz, have been published,14 and also
the corresponding 13C chemical shifts for a series of a-
substituted camphors bearing 10 different substituents
1
including the halogens.15 The calculated H chemical
Short-range effects
shifts for the parent compounds norbornane and camphor
have been obtained, through the CHARGE routine, and
showed very good agreement with the experimental
results.11,16
The CHARGE scheme calculates the effects of neigh-
bouring atoms on the partial atomic charge of the atom
under consideration based upon classical concepts of
inductive and resonance contributions. If we consider an
atom I in a four-atom fragment I-J-K-L the partial atomic
charge on I (qI) is due to three effects. There is an a effect
from atom J given by the difference in the electro-
negativity of atoms I and J. A b effect from atom K
proportional to both the electronegativity of atom K and
the polarisability of atom I. There is also a g effect from
atom L given by the product of the atomic polarisabilities
of atoms I and L for I ¼ H and L ¼ F, Cl, Br, I. However,
for chain atoms (C, N, O, S etc.) the g effect (i.e. C—C—
C—H) is parameterised separately and is given by
A þ B cos u where u is the C—C—C—H dihedral angle
and A and B empirical parameters. Full details including
the appropriate equations are given in Ref. [16].
The norcamphors or norbornanones are better models
for such calculations, since they do not have the three
methyl groups attached to C-1 and C-7, and, thus, there is
no additional steric interaction with a substituent on the
C-3 carbon atom. Therefore, we present here a study of
these compounds all of which have a rigid geometry, with
no unusual steric effects, and bearing two geminal
functional groups: the 3-endo- and 3-exo-substituted
norbornanones (Z ¼ Cl, Br, I, OH, SMe and SeMe)
(Scheme 1). They were chosen as a probe to check
whether the CHARGE program, properly parametrised
for the carbonyl group,16 can be used to estimate the
proton chemical shifts for this series of disubstituted
compounds. We also compare the chemical shifts
predicted by CHARGE with those calculated by the
GIAO method.
The total charge is given by summing these effects and
the partial atomic charges (qI) converted to shift values
using the equation
It must be emphasised that despite the compounds
having been known for some decades (except the endo
iodo derivative and both isomers of methylthio and
methylseleno derivatives) the papers on these com-
d ¼ 160:84qI ꢀ 6:68
Long-range effects
(1)
1
pounds17–22 do not include the corresponding H-NMR
data. In several instances only the chemical shift for the
H-3 proton is given,20,21,23 or for groups of protons as
unresolved multiplets.22,24,25
The effects of distant atoms on the proton chemical shifts
are due to steric, anisotropic and electric field contri-
butions. H—H steric interactions are shielding in alkanes
and deshielding in aromatics and X—H (X ¼ C, O, Cl, Br,
I) interactions deshielding, according to a simple rꢀ6
dependence:
H7s
H7a
7
H1
dsteric ¼ aS=r6
where aS is the steric coefficient for any given atom.
(2)
1
H6x
O
6
2
The effects of the electric field of the C—X bonds
(X ¼ H, F, Cl, Br, I, O) on the C—H protons are obtained
from the component of the electric field along the
C—H bond. The electric field for a single bonded atom
H
4
n
6
3
Z3x
H5x
5
H4
H5n
Z3n
—
—
(e.g.
O) is calculated as due to the charge on the
9: Z3x=SMe; Z3n=H
10: Z3x=H; Z3n=SMe
11: Z3x=SeMe; Z3n=H
12: Z3x=H; Z3n=SeMe
5: Z3x=H; Z3n=Br
6: Z3x=I; Z3n=H
7: Z3x=H; Z3n=I
8: Z3x=OH; Z3n=H
1: Z3x=H; Z3n=H
2: Z3x=Cl; Z3n=H
3: Z3x=H; Z3n=Cl
4: Z3x=Br; Z3n=H
oxygen atom and an equal and opposite charge on the
attached carbon atom. The vector sum gives the total
electric field at the proton and the component of this field
along the C—H bond is proportional to the proton
chemical shift.
Scheme 1. Molecules studied and their numbering
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 376–383

378
G. F. GAUZE ET AL.
The magnetic anisotropy of a bond with cylindrical
symmetry (e.g. CꢁC) is obtained from the appropriate
EXPERIMENTAL
McConnell6 equation:
Compounds
Dxð3 cos2 ’ ꢀ 1Þ
For the separation of the diastereoisomers a HPLC Waters
˚
PrepLC 4000, with a C-18 100 A apolar column, and UV–
danis
¼
(3)
3R3
Vis Waters 484 detector, was used. Separations of
halonorbornanones isomers by preparative HPLC were
performed with methanol–water (4:1) as eluent and to 3-
methylthio and 3-methylselenonorbornanones isomers
with methanol–water (1:1).
In Eqn (3) R is the distance from the perturbing group
˚
to the nucleus of interest in A, w is the angle between the
vector R and the symmetry axis and Dx the molar
anisotropy of the CꢁC bond. (Dx ¼ xparl ꢀ xperp) where
xparl and xperp are the susceptibilities parallel and
perpendicular to the symmetry axis, respectively.
For a non-symmetric group such as the carbonyl group,
Eqn (3) is replaced by the full McConnell equation:
The 3-exo-chloronorbornanone (2) compound was
obtained from the reaction of norbornanone and sulphuryl
chloride,28 being purified through column chromatog-
raphy (70–230 silica gel, Aldrich, and CHCl3 as eluent),
yield 50%. The 3-endo-chloronorbornanone (3) was
obtained by epimerisation of 2 using sodium methoxide in
methanol. The isomers were obtained as a 2:1 (exo:endo)
mixture, and compound 3 was isolated by HPLC which
led to 7.5% of the pure endo-isomer. 3-exo-bromonor-
bornanone (4) was prepared by reacting norbornanone
with bromine in diethyl ether and purified by column
chromatography (70–230 silica gel, Aldrich, and CHCl3
as eluent), yield 72%. The epimerisation of 4 led to a 1:1
mixture of two isomers, which were also separated by
HPLC, yielding 23% of the pure endo-isomer. For the
preparation of the exo-iodo derivative, an iodine solution
in THF was added to the lithium enolate of norborna-
none.14 The mixture of diasteroisomers was obtained in
71% yield, which was analysed by GC-MS, showing a 3:1
proportion of the exo- (6) to the endo-isomer (7). The
isomers were separated by HPLC. The compound 8 (3-
exo-hydroxynorbornanone) was prepared according
Jauch,25 by the reaction of m-chloroperbenzoic acid with
norbornanone trimethylsilyl enol ether in dry pentane.
The 3-exo-methylthio derivative (9) was prepared by
Scholz’s29 method, being purified by distillation (b.p.
86 8C/1.6 mmHg), yield 47%. The epimerisation of (9)
led to a 1:1 mixture of two isomers exo and endo, which
were also separated by HPLC. The preparation of 3-exo-
methylselenonorbornanone was performed by Liotta30
method and purified by column chromatography flash
(230–400 silica gel, Aldrich, and hexane-ether 9:1 as
eluent), yield 22%. 3-endo-methylselenonorbornanone
(12) was obtained by epimerisation of 11 and isolated by
HPLC.
½Dxparlð3 cos2 u1 ꢀ 1Þ þ Dxperpð3 cos2 u2 ꢀ 1Þꢂ
danis
¼
3R3
(4)
where u1 and u2 are the angles between the radius vector R
and the x and z axes, respectively and Dxparl (xz ꢀ xx) and
Dxperp (xy ꢀ xx) are the parallel and perpendicular
—
anisotropy for the C O bond, respectively.
—
The effect of the excess p electron density at a given
carbon atom on the proton chemical shifts of the
neighbouring protons is given by Eqn (5) where Dqa
and Dqb are the excess p electron density at the a and b
carbon atoms, respectively. The p electron densities are
calculated using Huckel theory parameterised to repro-
duce the values obtained from ab initio calculations.1b
dp ¼ 10:0 Dqa þ 2:0 Dqb
(5)
The above contributions are added to Eqn (1) to give
the calculated shift of Eqn (6).
dtotal ¼ dcharge þ dsteric þ danis þ del þ dp
(6)
APPLICATION TO ALICYCLIC
DIFUNCTIONAL COMPOUNDS
For the norbornanones considered here all the short-range
—
effects, C(X)—C O, have already been parametrised in
—
previous papers of this series.16,26,27 The electric field
effect is calculated directly from the partial atomic
charges, thus the only long-range effects to consider are
the parallel and perpendicular anisotropies of the
carbonyl group and the CO steric effect. The steric
effect of the aliphatic CO group was found to be due
solely to the carbonyl oxygen. We assume the same for
these alicyclic systems and also use the values obtained
previously for the carbonyl group anisotropy and the
steric coefficient for the carbonyl oxygen, i.e. the
coefficient aS in Eqn (2) for the carbonyl oxygen.1b,11,16
The steric effect of selenium was fitted with a value of aS
Spectra
1H- and 13C-NMR spectra were obtained on a Varian
INOVA 500 spectrometer and Bruker DRX 500 operating
at 499.88 and 500.13 MHz for 1H and 125.70 and
125.77 MHz for C13, respectively. DEPT, gCOSY,
gHSQC and gHMBC experiments were also performed.
The spectra were recorded in 20 mg cmꢀ3 CDCl3
solutions with a probe temperature of ca. 300 K and
6
˚
of 100.0 A.
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 376–383

1H CHEMICAL SHIFTS IN NMR
379
referenced to TMS. Typical running conditions (1H
spectra) were 128 transients, spectral width 3250 Hz and
32 K data points zero-filled to 128 K. For the 2D
experiments were conducted using the standard Varian
sequences. 13C spectra were recorded using 512
transients, spectral width 32,000 Hz and 128 K data
points zero-filled to 512 K. For the gHMBC experiment a
J value of 8 Hz was used.
study of various deuterated norbornanone derivatives,33
and recently confirmed.11 The spectra of the remaining
compounds (2–12) were assigned using the well known
substituent effects and assisted by DEPT, gCOSY,
gHSQC and gHMBC experiments, as needed. The
1
experimental H and 13C chemical shifts are presented
in Tables 1 and 2, respectively.
RESULTS AND DISCUSSION
Theoretical calculations
We note that in Table 1 while some protons present almost
the same chemical shifts as the parent compound (1),
others are remarkably affected by the substituent. Thus,
the average values for H-1 (2.7), H-4 (2.7), H-6n (1.6) and
H-6x (1.8) are very close to the ones of compound 1 (2.6,
2.7, 1.5 and 1.8, respectively). However, the chemical
shifts for the remaining protons are deshielded either in
relation to 1 or from a set (exo or endo) in relation to the
other set. Thus, H-5n is deshielded in relation to H-5x (for
the endo derivatives), and H-5x in relation to H-5n (for the
exo derivatives), by ꢃ0.5 ppm. For H-7s and H-7a there is
a deshielding effect of 0.2 ppm for the endo derivatives in
relation to 1, while for the exo derivatives this occurs just
for H-7s (ꢃ0.6 ppm). These effects are almost the same
regardless of the substituent. However, for H-3n and H-3x
chemical shifts, which are highly affected by the
substituent, the deshielding effect increases with the size
of the substituent atom (for O, Cl, Br and I). Indeed for the
SMe and SeMe derivatives the deshielding increases with
the atom polarisability. This effect is larger for the endo
compounds.
All the structures were minimised using the Gaussian
98W program.31 For the SMe and SeMe derivatives were
constructed the potential energy surfaces (dihedral CH3—
Z—C3—C2) and was obtained two possible conformers
to exo isomers and three possible conformers to endo
isomers. All the compounds, except iodine derivatives
were optimised at B3LYP/6–311þG(d,p) level of theory.
For the iodine derivatives the 6–311þG(d,p) basis set
could not be used. In this case the 3–21G basis set was
used.
The chemical shifts were referenced to methane
(minimised and calculated in the same manner)
and converted to TMS using the methane experimental
chemical shift (d ¼ 0.23 ppm). In both programs,
the chemical shifts to SMe and SeMe derivatives, were
calculated using the weight average of the chemical shifts
to each conformer.
1
The H chemical shifts were calculated with GIAO
method and CHARGE8c program. The latter is available
as part of NMRPredict,32 a modelling, 1H and 13C
software package.
The substituent effect on the two protons 5, for both
series, is due to all the long-range effects and not just to
the steric effect since they are very similar for all
substituents. A smaller but similar effect is observed for
the proton H-7s of the exo compounds. For the proton H-
7a, which is far from the substituent in the endo-
derivatives, the W arrangement between H-7a and the
SPECTRAL ASSIGNMENTS
The assignments of the spectra of the parent compound,
norbornanone (1), had been already reported from the
Table 1. 1H Chemical Shifts (ppm)a for 3-endo- and 3-exo-substituted norbornanones
Substituent
Atom
5n
1
3x
3n
4
5x
6x
6n
7s
7a
CH3
H
2.59 (d) 2.06 (dd) 1.84 (dd) 2.67 (s) 1.80 (m) 1.44 (m) 1.81 (m) 1.52 (dd) 1.73 (m) 1.56 (d)
exo 2.72 (s) 3.67 (d) 2.73 (s) 1.95 (m) 1.49 (m) 1.85 (m) 1.55 (m) 2.27 (m) 1.60 (m)
endo 2.76 (d) 4.13 (d) 2.81 (s) 1.69 (m) 2.03 (m) 1.91 (m) 1.58 (m) 1.83 (m) 1.78 (m)
exo 2.73 (d) 3.83 (d) 2.79 (d) 1.97 (m) 1.52 (m) 1.84 (m) 1.57 (m) 2.30 (m) 1.63 (m)
endo 2.75 (d) 4.32 (d) 2.83 (s) 1.74 (m) 2.06 (m) 1.89 (m) 1.56 (m) 1.91 (m) 1.85 (m)
exo 2.69 (dd) 4.14 (d) 2.81 (s) 1.90 (m) 1.59 (m) 1.81 (m) 1.57 (m) 2.28 (m) 1.68 (m)
endo 2.73 (d) 4.64 (s) 2.77 (s) 1.81 (m) 2.00 (m) 1.74 (m) 1.48 (m) 2.02 (m) 1.94 (m)
exo 2.60 (dd) 3.52 (dd) 2.56 (d) 1.81 (m) 1.42 (m) 1.83 (m) 1.50 (m) 2.17 (m) 1.57 (m)
—
—
—
—
—
—
—
—
Cl
Br
I
—
—
—
—
—
—
OH
—
Sme exo 2.67 (d)
endo 2.68 (d) 3.20 (d)
SeMe exo 2.68 (d)
endo 2.69 (d) 3.47 (d)
—
2.72 (d) 2.53 (d) 1.88 (m) 1.50 (m) 1.86 (m) 1.55 (m) 2.20 (m) 1.48 (m) 2.25 (s)
2.76 (s) 1.63 (m) 1.95 (m) 1.86 (m) 1.52 (m) 1.77 (d) 1.71 (d) 2.22 (s)
3.02 (d) 2.57 (d) 1.88 (m) 1.48 (m) 1.82 (m) 1.56 (m) 2.18 (m) 1.50 (d) 2.17 (s)
2.74 (d) 1.53 (m) 1.90 (m) 1.85 (m) 1.68 (m) 1.82 (d) 1.76 (d) 2.13 (s)
—
—
—
a In CDCl3 as solvent. Signal multiplicities are indicated as singlet (s), doublet (d), double doublet (dd) and multiplet (m).
Copyright # 2006 John Wiley & Sons, Ltd. J. Phys. Org. Chem. 2006; 19: 376–383

380
G. F. GAUZE ET AL.
Table 2. 13C Chemical Shifts (ppm)a for 3-endo- and 3-exo-substituted norbornanones
Substituent
Atom
1
2
3
4
5
6
7
CH3
H
Cl
49.9
48.6
48.8
49.1
48.3
49.8
47.2
48.1
49.0
50.1
49.6
49.8
218.3
210.5
210.2
210.8
210.2
212.2
211.9
217.5
213.8
214.9
214.8
215.6
45.3
59.3
63.5
49.6
55.2
28.1
35.3
75.7
53.6
57.3
46.2
50.3
35.4
44.2
42.2
44.5
44.2
45.7
42.8
41.5
41.5
40.1
42.1
40.6
27.2
25.6
20.8
26.3
22.7
27.1
26.5
24.3
27.1
21.9
27.7
23.8
24.2
23.7
25.6
23.5
25.1
23.0
24.6
23.5
24.8
25.2
24.7
24.9
37.7
34.3
34.4
35.0
35.7
36.5
36.2
34.3
35.5
36.5
36.4
37.4
—
—
—
—
—
—
—
—
15.2
15.4
5.2
4.5
exo
endo
exo
endo
exo
endo
exo
exo
endo
exo
endo
Br
I
OH
SCH3
SeCH3
a In CDCl3 as solvent.
halogen atom seems to be responsible for the favourable
interaction between the involved orbitals (Scheme 2).34
The complete SCS data for all 3-substituted norborna-
nones studied are given in Table 3.
Despite the apparent absence of a steric effect between
H-5n and the substituent, there is a shielding effect for the
C-5 chemical shift (Table 2) in compounds 3 (endo-Cl), 5
(endo-Br), 10 (endo-SMe), 12 (endo-SeMe), and not for
compound 7 (endo-I). This could indicate a steric
compression between the substituent and H-5n, which
does not occur for the iodo-derivative due to the long C—I
bond length in comparison to C—Z (Z ¼ Br, Cl, S, Se)
bonds. No significant shielding or deshielding effect is
observed for C-1, C-4, C-6 and C-7, within the two sets of
the substituted norbornanones (2–12). Obviously, C-3 is
deshielded due to the a-substituent effect, but to a smaller
extent than for the corresponding norbornanes, which
may due to the occurrence of an interaction between nX
and pꢄCO orbitals.13
H7a
Z
The experimental chemical shifts are compared with
the CHARGE and ab initio GIAO calculated values given
Scheme 2. W arrangement between H-7a and the substi-
tuent Z
Table 3. SCS values for 3-substituted norbornanones (ppm)a
Substituent
endo
exo
OH
Atom
Hb
Cl
Br
I
SMe
SeMe
Cl
Br
I
SMe
SeMe
1
2.59
2.06
1.84
2.67
1.80
1.44
1.81
1.52
1.73
1.56
—
0.17
2.07
—
0.16
2.26
—
0.14
2.58
—
0.09
1.14
—
0.10
1.14
—
0.13
—
0.14
—
0.10
—
0.01
—
0.08
—
0.09
—
3x
3n
4
5x
5n
6x
6n
7s
7a
1.83
0.06
0.15
0.05
0.04
0.03
0.54
0.04
—
1.99
0.12
0.17
0.085
0.03
0.05
0.57
0.07
—
2.30
0.14
0.10
0.15
0.00
0.05
0.55
0.12
—
1.68
ꢀ0.11
0.01
ꢀ0.02
0.02
ꢀ0.02
0.44
0.01
—
0.88
ꢀ0.14
0.08
0.06
0.05
0.03
0.47
ꢀ0.08
2.25
1.18
ꢀ0.10
0.08
0.04
0.01
0.04
0.45
ꢀ0.06
2.17
0.14
ꢀ0.11
0.59
0.10
0.06
0.10
0.22
—
0.16
ꢀ0.06
0.62
0.08
0.04
0.18
0.29
—
0.10
0.01
0.56
ꢀ0.07
ꢀ0.04
0.29
0.38
—
0.09
ꢀ0.17
0.51
0.05
0.00
0.04
0.15
2.22
0.07
ꢀ0.27
0.46
0.04
0.16
0.09
0.20
2.13
c
CH3
a In CDCl3 as solvent.
b d for the norbornanone molecule.
c d for the substituent methyl protons.
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 376–383

1H CHEMICAL SHIFTS IN NMR
381
Table 4. Experimental versus calculated 1H chemical shifts (ppm) for 3-exo-substituted norbornanones and root-mean-square
error (r.m.s)
Substituent
Atom
6x
1
3n
4
5x
5n
6n
7s
7a
CH3
r.m.s
Cl exo
CDCl3
2.72
2.78
2.36
2.73
2.78
2.42
2.69
2.76
2.50
2.60
2.70
2.29
2.67
2.74
2.41
2.68
2.74
2.47
3.67
3.68
3.37
3.83
3.94
3.54
4.14
4.16
3.20
3.52
3.55
3.40
2.72
2.95
2.26
3.02
3.08
2.51
2.73
2.74
2.41
2.79
2.79
2.48
2.81
2.84
2.41
2.56
2.50
2.42
2.53
2.92
2.28
2.57
2.58
2.29
1.95
1.92
1.83
1.97
1.90
1.89
1.90
1.87
1.89
1.81
1.92
1.77
1.88
1.89
1.82
1.88
1.87
1.85
1.49
1.51
1.29
1.52
1.50
1.34
1.59
1.48
1.30
1.42
1.48
1.30
1.50
1.40
1.37
1.48
1.41
1.39
1.85
1.79
1.72
1.84
1.76
1.72
1.81
1.75
1.68
1.83
1.88
1.74
1.86
1.82
1.73
1.82
1.80
1.73
1.55
1.66
1.39
1.57
1.62
1.40
1.57
1.61
1.35
1.50
1.79
1.41
1.55
1.62
1.42
1.56
1.61
1.44
2.27
2.45
2.19
2.30
2.54
2.25
2.28
2.55
2.26
2.17
2.08
2.14
2.20
2.29
2.24
2.18
2.04
2.21
1.60
1.51
1.36
1.63
1.52
1.35
1.68
1.51
1.34
1.57
1.62
1.41
1.48
1.59
1.42
1.50
1.59
1.26
—
—
—
CHARGE
GIAO
CDCl3
CHARGE
GIAO
CDCl3
CHARGE
GIAO
CDCl3
CHARGE
GIAO
CDCl3
CHARGE
GIAO
CDCl3
CHARGE
GIAO
0.08
0.21
—
0.10
0.20
—
0.12
0.29
—
0.12
0.14
—
0.16
0.21
—
0.07
0.22
Br exo
—
—
I exo
—
—
OH exo
SMe exo
SeMe exo
2.25
2.12
2.22
2.17
2.24
2.11
in Tables 4 and 5. There is a very good agreement between
the experimental and CHARGE data. Only for a few
cases, as for the 3-endo and 3-exo protons in SMe
derivatives, were deviations larger than 0.2 ppm observed,
but most data showed small deviations ranging from 0.01
to 0.13 ppm. For all 11 compounds with 163 different 1H
chemical shifts, the CHARGE gave an r.m.s error ranging
from 0.07 to 0.16 ppm, which is satisfactory. There is a
significant difference in the calculated shifts of H-5n and
H-6n in the exo-derivatives (r.m.s average ¼ 0.07 ppm) in
relation to the endo-derivatives (r.m.s avera-
ge ¼ 0.17 ppm), indicating that the program is over-
estimating the substituent effects for the last set.
The calculated shifts from the quantum mechanical
GIAO calculations are also given in Tables 4 and 5. They
are in general less accurate than the CHARGE
calculations as it was noted in a previous paper.35 The
3-21G basis set used for iodo compounds is too inaccurate
to be of use in 1H NMR calculations. This suggests that in
the halogen family post-third-row atoms (post-Br) cannot
Table 5. Experimental versus calculated 1H chemical shifts (ppm) for 3-endo-substituted norbornanones and root-mean-
square error (r.m.s)
Substituent
Atom
6x
1
3x
4
5x
5n
6n
7s
7a
CH3
—
r.m.s
Cl endo
CDCl3
2.76
2.77
2.37
2.75
2.77
2.39
2.73
2.73
2.37
2.68
2.66
2.34
2.69
2.73
2.37
4.13
4.11
3.90
4.32
4.35
4.16
4.64
4.60
4.09
3.20
3.66
2.65
3.47
3.41
2.94
2.81
2.73
2.50
2.83
2.78
2.52
2.77
2.83
2.25
2.76
2.97
2.53
2.74
2.94
2.53
1.69
1.66
1.54
1.74
1.69
1.60
1.81
1.68
1.54
1.63
1.74
1.52
1.53
1.75
1.55
2.03
2.14
2.08
2.06
2.25
2.18
2.00
2.28
2.80
1.95
2.05
1.95
1.90
1.95
1.80
1.91
1.77
1.79
1.89
1.78
1.80
1.74
1.75
1.66
1.86
1.80
1.78
1.85
1.78
1.77
1.58
1.74
1.52
1.56
1.75
1.56
1.48
1.71
1.51
1.52
1.74
1.65
1.68
1.74
1.67
1.83
1.96
1.53
1.91
1.95
1.61
2.02
1.95
1.57
1.77
1.82
1.55
1.82
1.85
1.60
1.78
1.73
1.55
1.85
1.71
1.62
1.94
1.68
1.71
1.71
1.71
1.51
1.76
1.74
1.55
—
CHARGE
GIAO
CDCl3
CHARGE
GIAO
CDCl3
CHARGE
GIAO
CDCl3
CHARGE
GIAO
CDCl3
0.10
0.20
—
0.09
0.19
—
0.16
0.43
—
0.12
0.23
—
Br endo
—
I endo
—
SMe endo
SeMe endo
2.22
2.13
2.29
2.13
2.05
2.15
CHARGE
GIAO
0.11
0.22
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 376–383

382
G. F. GAUZE ET AL.
4.50
4.00
3.50
3.00
2.50
2.00
1.50
1.00
produces the largest number of best hits (75%), while
GIAO is better only in 25% of the hits.
The comparative study for these disubstituted com-
pounds shows that the calculations by CHARGE better
reproduce the experimental shifts than the GIAO
calculations.
CHARGE
GIAO
CONCLUSIONS
1
Unequivocal assignments for the H and 13C chemical
shifts of the 3-endo- and 3-exo-substituted norbornanones
with Cl, Br, I, SMe and SeMe substituents and 3-
hydroxynorbornanone, were deduced from the 1D spectra
at 500 MHz, using the DEPT sequence and the 2D
gCOSY, gHSQC and gHMBC experiments. The calcu-
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
δexp (ppm)
1
lated H chemical shifts using the CHARGE8c routine
Figure 1. Scatter plot of experimental versus predicted
chemical shifts for 3-exo-substituted norbornanones
were in good agreement with the experimental results.
The r.m.s error for each compound was in the range 0.07–
0.17. The GIAO are less accurate than the CHARGE
calculations when assessed by scatter plots, r.m.s. errors
and number of best hits. CHARGE provides a rapid and
practical useful tool, which can be used to give reliable 1H
chemical shift predictions 3-substituted 2-norbornanones.
be calculated to any meaningful precision using this
method (r.m.s error 0.29 and 0.43 for exo and endo
derivatives, respectively).
To eliminate the importance of a predictor and see how
good the correlation between calculated versus exper-
imental data is, we compiled the data set in scatter plots.
The scatter plot (Figs. 1 and 2) shows that, in general, the
results calculated through the CHARGE program slightly
overestimate the observed chemical shifts. Moreover, 1H
chemical shifts calculated using the GIAO method are
underestimated. The correlation coefficient, r, is 0.98 for
CHARGE and 0.96 for GIAO. The r.m.s. error values are
0.11 for CHARGE and 0.23 for GIAO. We also analysed
the data to see which model produces the greatest number
of hits closest to the observed chemical shifts. CHARGE
Acknowledgements
We thank FAPESP for the financial support of this
research and for a scholarship (to M.G.C.), Capes for
scholarship to G.F.G and CNPq for a fellowship (to R.R.
and E.A.B). CENAPAD-SP is gratefully acknowledged
for the computer facilities (Gaussian98). We also thank
Dr. S. A. Rocco for recording the NMR spectra.
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