A 13C and 15N experimental NMR and theoretical study of the structure of linear primary aliphatic amines and ammonium salts: From C1 to C18

Article abstract of DOI:10.1016/j.tet.2011.04.067

Eighteen aliphatic linear amines, from methylamine to stearylamine, have been experimentally studied by NMR and theoretically calculated at the GIAO/B3LYP/6-311++G(d,p) level. A partial exploration of their conformation has been carried out, mainly to determine the effect on the chemical shifts. In solution and for neutral amines, ¹⁵N chemical shifts indicate a mixture of two conformations. In the solid state (CPMAS NMR) only the subset of solid amines has been studied (from C14 to C18). The ¹⁵N signals of the corresponding ammonium salts in the solid state depend on the counteranions, Cl^- and CF₃CO₂^-, a result that is theoretically proven.

Full text of DOI:10.1016/j.tet.2011.04.067

Tetrahedron 67 (2011) 4633e4639
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
13
15
A C and N experimental NMR and theoretical study of the structure of linear
primary aliphatic amines and ammonium salts: from C1 to C18
,
a
,
a
b
b
Dionisia Sanz a , Rosa M. Claramunt , M. Angeles García , Ibon Alkorta , Jose Elguero
ꢀ
*
*
ꢀ
a
ꢀ
ꢀ
Departamento de Química Organica y Bio-Organica, Facultad de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain
b
ꢀ
Instituto de Química Medica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Eighteen aliphatic linear amines, from methylamine to stearylamine, have been experimentally studied
by NMR and theoretically calculated at the GIAO/B3LYP/6-311þþG(d,p) level. A partial exploration of
their conformation has been carried out, mainly to determine the effect on the chemical shifts. In so-
lution and for neutral amines, 15N chemical shifts indicate a mixture of two conformations. In the solid
state (CPMAS NMR) only the subset of solid amines has been studied (from C14 to C18). The 15N signals of
Received 24 February 2011
Received in revised form 12 April 2011
Accepted 15 April 2011
Available online 21 April 2011
the corresponding ammonium salts in the solid state depend on the counteranions, Clꢀ and CF3CO2
a result that is theoretically proven.
,
ꢀ
Keywords:
Amines
13C NMR
15N NMR
CPMAS
Ó 2011 Elsevier Ltd. All rights reserved.
GIAO
DFT study
1. Introduction
octylamine (caprylamine) (8), nonylamine (9), decylamine (10),
undecylamine (11), dodecylamine (laurylamine) (12), tridecylamine
(13), tetradecylamine (myristylamine) (14), pentadecylamine (15),
hexadecylamine (palmitylamine) (16), heptadecylamine (margar-
ylamine) (17) and octadecylamine (stearylamine) (18). Actually, data
for 1 and 2 come from the literature and no experimental data will
correspond to 17, a non-commercial product, although it has been
approached theoretically.
Although for most functional groups and ring systems it can be
said that they are part of bioactive compounds and materials,1 this is
only partly true for linear aliphatic amines (alkylamines or alkane-
1-amines according to IUPAC nomenclature). The influence of the
chain length (methyl, ethyl, butyl) of 8-alkylamino analogues of an
adenosine derivative was studied in haemodynamic response.2 The
fact that aliphatic amines decrease the hERG binding affinity has
been reported.3 We should note that this family of compounds has
been the subject of NMR studies almost from the beginning of each
nucleus, in particular 13C4e6 and 15N.7 We have devoted during the
years some papers to these compounds: effect on the 13C chemical
shifts produced by the protonation of amines;8 comparison of 13C
chemical shifts of amines and N-alkyl pyridinium salts;9 influence of
the conformation of amines (mainly cyclic) on 1H, 13C and 15N
chemical shifts;10 determination of the structure of fatty amines
with 16 and 18 carbon atoms by NMR.11,12 We have also studied by
NMR the protonation of 2-pyrazolines using amines as models.13,14
None of these NMR publications being comprehensive, we de-
cided to study the following 18 amines and their cations: methyl-
amine (1), ethylamine (2), propylamine (3), butylamine (4),
pentylamine (amylamine) (5), hexylamine (6), heptylamine (7),
2. Results and discussion
We will discuss first the calculated energies (36 compounds)
and then the NMR results (34 compounds) both in solution and in
the solid state. The energy calculations were carried out at the
B3LYP/6-311þþG(d,p) level and the obtained optimized geometries
served for the GIAO calculations of absolute shieldings (see
Computational details).
2.1. Energies
For the 18 compounds we have calculated four conformations
(for the simplest derivatives some of them are identical). This is only
avery minor part of the total conformational space even considering
only 60ꢁ rotations of staggered situations. We have reported pre-
viously10 that the calculated absolute shieldings (
s, ppm) of the
* Corresponding authors. E-mail addresses: dsanz@ccia.uned.es (D. Sanz),
rclaramunt@ccia.uned.es (R.M. Claramunt).
adjacent methylene group are dependent on their orientation
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.067

4634
D. Sanz et al. / Tetrahedron 67 (2011) 4633e4639
Table 2
relative to the N lone pair. So we have explored two conformations of
the amino group (Fig. 1), the Cs and the C1, maintaining the fully
extended all-trans structure for the aliphatic chain.15
Absolute energies (hartree) and proton affinities (kJ molꢀ1) calculated at the B3LYP/
6-311þþG(d,p) level for ammonium cations
Ammonium
Absolute
PA
PAþZPE
Experimental PA
NH4
1Hþ
2Hþ
3Hþ
4Hþ
5Hþ
6Hþ
7Hþ
8Hþ
9Hþ
þ
ꢀ56.58272
ꢀ96.249058
ꢀ135.58203
ꢀ174.90843
ꢀ214.23389
ꢀ253.55891
ꢀ292.88362
ꢀ332.20819
ꢀ371.53267
ꢀ410.85711
ꢀ450.18151
ꢀ489.50590
ꢀ528.83026
ꢀ568.15464
ꢀ607.47898
ꢀ646.80334
ꢀ686.12767
ꢀ725.45204
ꢀ764.77637
886.5
932.5
946.5
951.6
954.9
956.6
957.5
958.2
958.5
958.8
958.9
959.1
959.1
959.2
959.2
959.3
959.3
959.3
959.3
846.5
892.2
906.8
911.8
915.1
916.9
917.9
918.4
918.9
853.6
899.0
912.0
917.8
921.5
923.5
927.5
923.2
928.9
H H H
H
H H
H H
H
H
H
6
rotation
3
5
N
1
CH3
N
CH3
2
4
H
about C1-N
H H H H H
Cs methyl staggered
H H
H
H
H
H
H
C1 methyl staggered
C2
C2
CH3
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
C
C
N
N
H
4
4
10Hþ
11Hþ
12Hþ
13Hþ
14Hþ
15Hþ
16Hþ
17Hþ
18Hþ
919.3
930.4
H
H
C3
C3
rotation
about C4-C5
rotation
about C4-C5
H
H H H
N
H
H H
H H
H
H
rotation
H
N
H
about C1-N
H
H H H H H
H H
H
H
H
CH3
CH3
C1 methyl rotated (from C1)
C1 methyl rotated (from Cs)
C2
N
C2
H
H
(this is similar to odd/even dichotomy in alkanes boiling and
melting points):16
H
H
H
H
H
H
H
H
H
H
H
H
C
C
N
H
4
4
H
CH3
CH3
m
even [ð1:466 ꢂ 0:001ÞLð0:169 ꢂ 0:003Þ1=C;n[9;R2 [0:998 (1)
C3
C3
m
odd [ð1:520 ꢂ 0:001ÞLð0:184 ꢂ 0:001Þ1=C;n[9;R2 [1:000 (2)
Fig. 1. The four studied conformations in the case of hexylamine (6). They correspond
to the rotation of the amino group (C1eN bond) and to the rotation of the C4eC5 bond.
The dipole moment of methylamine (1) has been measured in
the gas phase to be between 1.24 and 1.35 D17 that compares well
with the value we have calculated, 1.41 D.
We have pointed out, in our work on long-chain fatty amines,11
that the chemical shifts of the terminal methyl groups are not well
reproduced by the calculations of the Cs structure; for this reason,
we decided to rotate 60ꢁ the methyl group about the nꢀ1 bond
(C16eC17 for 18 and C15eC16 for 17 and so on). The resulting
structures are of C1 symmetry. The energetic results are reported in
Tables 1 and 2.
Having calculated all amine/ammonium pairs, we have obtained
the proton affinities, PA in kJ molꢀ1 (Table 2), and compared them
with the ten available experimental values found in the NIST da-
tabase.18 The values are linearly related,
Table 1
Absolute (hartree) and relative energies (kJ molꢀ1) calculated at the B3LYP/6-311þþG(d,p) level for amines
Amine
Cs
C1
Cs Me rotated
C1 Me rotated
Absolute
Relative
Relative
Absolute
Absolute
Relative
Absolute
Relative
1
2
3
4
5
6
7
8
ꢀ95.89389
ꢀ135.22152
ꢀ174.54597
ꢀ213.87019
ꢀ253.19457
ꢀ292.51891
ꢀ331.84325
ꢀ371.16760
ꢀ410.49193
ꢀ449.81628
ꢀ489.14061
ꢀ528.46496
ꢀ567.78929
ꢀ607.11363
ꢀ646.43795
ꢀ685.76231
ꢀ725.08664
ꢀ764.41098
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
ꢀ95.89389
ꢀ135.22154
ꢀ174.54581
ꢀ213.87004
ꢀ253.19442
ꢀ292.51875
ꢀ331.84309
ꢀ371.16743
ꢀ410.49177
ꢀ449.81611
ꢀ489.14045
ꢀ528.46479
ꢀ567.78912
ꢀ607.11346
ꢀ646.43780
ꢀ685.76213
ꢀ725.08647
ꢀ764.41081
0.00
ꢀ0.04
0.43
0.39
0.39
0.42
0.41
0.44
0.42
0.45
0.43
0.46
0.45
0.45
0.42
0.45
0.45
0.46
ꢀ95.89389
ꢀ135.22152
ꢀ174.54526
ꢀ213.86876
ꢀ253.19325
ꢀ292.52018
ꢀ331.84190
ꢀ371.16625
ꢀ410.49060
ꢀ449.81494
ꢀ489.13928
ꢀ528.46362
ꢀ567.78795
ꢀ607.11228
ꢀ646.43662
ꢀ685.76096
ꢀ725.08530
ꢀ764.40964
0.00
0.00
1.86
3.75
3.44
3.51
3.53
3.54
3.51
3.53
3.51
3.53
3.51
3.54
3.51
3.54
3.53
3.53
ꢀ95.89389
ꢀ135.22154
ꢀ174.54513
ꢀ213.86879
ꢀ253.19312
ꢀ292.51741
ꢀ331.84175
ꢀ371.16609
ꢀ410.49043
ꢀ449.81477
ꢀ489.13911
ꢀ528.46344
ꢀ567.78778
ꢀ607.11211
ꢀ646.43645
ꢀ685.76079
ꢀ725.08513
ꢀ764.40947
0.00
ꢀ0.04
2.20
3.69
3.81
3.95
3.94
3.98
3.95
3.97
3.96
3.99
3.97
3.98
3.95
3.99
3.98
3.98
9
10
11
12
13
14
15
16
17
18
Besides the data reported in Tables 1 and 2, we have calculated
the dipole moments that are comprised between 1.41 (1) and 1.54
D (18) for the Cs and 1.21 (18) and 1.33 D (5) for the C1. There is
a linear variation of the dipole moment with the inverse of the
number of carbons (1/C) if even and odd numbers are separated
PAexp [Lð53 ꢂ 32ÞDð1:02 ꢂ 0:03ÞPAcalc;n[10;R2 [0:991 (3)
the large intercept is partly due to our values not having been cor-
rected for ZPE effects. With this correction, the intercept become
not significant and the correlation slightly improves,

D. Sanz et al. / Tetrahedron 67 (2011) 4633e4639
4635
PAexp [ Lð7:5 ꢂ 29:9ÞDð1:02 ꢂ 0:03ÞPAcalcDZPE;
n [ 10; R2 [ 0:992
(4)
Note that the experimental value for the C7 amine, 923.2 kJ molꢀ1, is
certainly wrong (a value about 928 kJ molꢀ1 is expected from the
calculations and from internal consistency). We have observed
that PAcalc increases linearly with 1/C,
PAcalcd [ ð961:6 ꢂ 0:2ÞLð29:1 ꢂ 0:5Þ1=C; n [ 18; R2 [ 0:994
(5)
Eq. 5 means that for large number of carbon atoms, the PA of the
amine will be close to 961 kJ molꢀ1
.
High-level calculations of the proton affinities of some amines
have been carried out by Maksic and Vianello19 [MP2(fc)/6-
311þG(d,p)//B3LYP/6-31G
*
þZPVE(B3LYP/6-31G(d))] for NH4
þ
, 1Hþ,
2Hþ and 3Hþ¼854.0, 897.9 and 908.8 kJ molꢀ1, by Raabe et al.20
[ZPEþMP2/6-311þþG(d,p)//HF/6-311þþG(d,p)] for NH4
þ,
1Hþ,
2Hþ, 3Hþ, 4Hþ and 5Hþ¼856.5.0, 900.8 and 912.1, 916.3 and
918.8 kJ molꢀ1, and by Vianello et al.21 [ROMP2(fc)/6-311þG(d,p)//
B3LYP/6-31G(d)] for NH4
þ
and 1Hþ, 2Hþ¼853.5 and 899.1 kJ molꢀ1
.
Note finally that the rotation of the amino group from Cs to C1
produces a very low increase in energy, about 0.4 kJ molꢀ1, but that
the rotation of the CeC(methyl) bond increases the energy by about
3.5e4 kJ molꢀ1, i.e., the first one should be able to compete with the
Cs but not so, or much less, the second one.
2.2. NMR in solution. Neutral molecules (amines)
The GIAO/B3LYP/6-311þþG(d,p) calculated absolute shieldings
(s, ppm) have been transformed into chemical shifts (d, ppm) by
means of two empirical equations that we have established using
a large and diversified collection of data:22
d
13CðppmÞ [ 175:7L0:963
s
13C ppm
(6)
(7)
d
15NðppmÞ [ L152:0L0:946
s
15N ppm
2.2.1. 15N NMR. We have tried a multiple regression to determine
the contributions of the Cs and C1 conformations to the experi-
mental chemical shifts (Table 3), of the form:
15
d
N
[ a
d
15NcalcCsDb
d
15NcalcC1
(8)
exp:
The result is highly satisfactory since we found a¼0.755 and
b¼0.245 (n¼17, R2¼1.000), that is, aþb¼1.000. Having tried this
kind of models many times, in general, aþb are, at the best, close to
1 but sometimes one of them is negative, which is devoid of
physical meaning. Eq. 8 means that the all-trans Cs conformation is
predominant but that there is about 25% of a conformation where
the amino group is rotated (see Fig. 1). Actually, since there are two
C1 conformers (gauche and gauche0) it results that there is 75.5% Cs,
12.25% C1 gauche, 12.25% C1 gauche0, which is fairly consistent with
the energy results (Table 1).
2.2.2. 13C NMR. Our attempts to use equations similar to Eq. 8 but
with four terms corresponding to the four conformations repre-
sented in Fig. 1 failed. Table 3 results show that from 6 to 18 there is
a regular trend that can be summarized like this (values in ppm):
29.6
n
33.8
42.3
22.6
NH2
14.0
H3C
31.8
26.8
n = 0 (6) to n = 12 (18)

4636
D. Sanz et al. / Tetrahedron 67 (2011) 4633e4639
The best fit was obtained using dummies (0 absent, 1 present)
for carbons C1, C2, C3, C4 and for the methyl group:
13
d
C
[ Lð3:0 ꢂ 0:3ÞDð0:940 ꢂ 0:009Þ
d
13CcalcDð1:04 ꢂ 0:14ÞC1
exp:
Lð3:51 ꢂ 0:11ÞC2Dð0:61 ꢂ 0:08ÞC3Lð0:23 ꢂ 0:08ÞC4
Dð3:09 ꢂ 0:19ÞMe; n [ 154; R2 [ 0:998
(9)
The fact that this equation has
a significant intercept,
3.0ꢂ0.3 ppm and a slope different from 1.000, means that Eq. 6 is
not totally adequate. This is due to the fact that this equation was
established using 461 sp, sp2, sp3 and aromatic carbon atoms linked
to other carbons but also to oxygen and nitrogen atoms, while now
we have only sp3 carbon atoms linked to other sp3 carbon atoms
and one of them to an sp3 nitrogen atom.
The
a (C1), b (C2), g (C3) and d (C4) effects (alternate signs) mean
that the Cs conformation alone is not enough to describe this part of
the molecule. It is known that the effects of the amino group along
an alkyl chain are important and affect the four or five first posi-
tions: 29.3 (
a
), 11.3 (
b
), ꢀ4.6 (
g) and 0.6 ppm (d
).4,5
To describe correctly the methyl signal a large correction of
þ3.1 ppm is necessary. This correction cannot be avoided by in-
troducing the calculation with the rotated methyl group (Fig. 1).
However, the differences between experimental values and calcu-
lated ones (excluding 1 and 2) are ꢀ0.84 (75% Cs to 25% C1), þ1.15
(75% Cs Me rotated to 25% C1 Me rotated) and 0.16 ppm (an average
of the two preceding ones). Thus, the rotation of the methyl is
implicated in the anomaly of the chemical shifts for the terminal
methyl groups.
The two worse points are carbons C1 of methylamine (1), exp.
28.30, fitted 28.85, residual ꢀ0.55 ppm and C2 of ethylamine (2),
exp. 18.90, fitted 17.98, residual þ0.92 ppm, both methyl groups
and both from the literature (DMSO-d6 instead of CDCl3).4e6,23
2.3. NMR in solution. Protonated molecules (ammonium
cations in CF3CO2H solution)
In the case of protonated amines (Table 4), there is only a pos-
þ
sible conformation for the eNH3 group, but it remains the prob-
lem of the methyl group as in neutral amines.
2.3.1. 15N NMR. We have tried two models, one using Cs (the major
conformation), Eq. 10, and another using a linear combination of
75.5% of Cs and 24.5% of C1 for the amines, Eq. 11, together with
a dummy (0 for amines, 1 for ammonium cations) both yielding
similar results in what R2 is concerned:
d
15Nexp [ ð1:002 ꢂ 0:004Þ
d
15NcalcLð1:55 ꢂ 0:20Þcation;
n [ 34; R2 [ 1:000
(10)
(11)
d
15Nexp [ ð1:000 ꢂ 0:004Þ
d
15NcalcLð2:31 ꢂ 0:19Þcation;
n [ 34; R2 [ 1:000
Note that the values for 1 and 2 are from the literature (hy-
drochlorides in methanol solution).7,24
2.3.2. 13C NMR. We have tried an equation (Eq. 12) similar to that
used for neutral amines (Eq. 9):
d
13Cexp [ Lð6:0 ꢂ 0:6ÞDð1:00 ꢂ 0:02Þ
d
13CcalcdLð4:8 ꢂ 0:3ÞC1
Dð0:1 ꢂ 0:1ÞC2Dð1:5 ꢂ 0:2ÞC3Lð0:4 ꢂ 0:1ÞC4
Dð3:3 ꢂ 0:3ÞMe; n [ 154; R2 [ 0:996
(12)

D. Sanz et al. / Tetrahedron 67 (2011) 4633e4639
4637
The coefficients are rather different and again a similar correc-
tion corresponds to the methyl group. The two worse points are
carbons C1 and C2 of ethylamine (2), exp. 35.0, fitted 37.0, residual
ꢀ2.0 ppm and exp. 12.9, fitted 11.1, residual þ2.8 ppm, both from
the literature (hydrochloride in methanol instead of CF3CO2H).23
were prepared by adding the stoichiometric amount of aqueous
hydrochloric acid (37%) to a methanol solution of 4 and 18. The
CPMAS results are gathered in Table 6.
The 13C Dd values are similar to those obtained in solution (see
Supplementary data) although less regular in part because some
signals are splitted, a common phenomenon in CPMAS NMR.28 The
most curious feature is that observed on 15N, while in solution
the effect is about þ6 ppm [8.4ꢀ2.3(solvent effect)z6 ppm], in the
solid state is about þ4 ppm for the trifluoroacetates but þ15 ppm
for the 18HþClꢀ.
2.4. Comparison between neutral and protonated amines
The protonation chemical shift effects, Dd
¼
d (ammonium cati-
ons)ꢀ (neutral amines), obtained using the data of Tables 3 and 4
d
To understand this apparent anomaly we have prepared 4HþClꢀ
and recorded its 15N and 13C CPMAS NMR spectra: ꢀ332.6 ppm
are reported in Supplementary data. The experimental 15N NMR
signals of the cations (compare Tables 3 and 4) are shifted þ8.4 ppm
from those of the corresponding amines save in the case of me-
thylamine (1) where the effect is much larger, þ15.9 ppm.7 These
values include the solventeffect, in ourcase, trifluoroacetic acid, that
has been estimated in þ2.3 ppm.14 For phenethylamine and homo-
veratrylamine effects of þ9.9 and 8.8 ppm have been, respectively,
reported, when comparing the 15N chemical shifts obtained in CDCl3
with those found in a solution of 5% of CF3CO2H in CDCl3.25
(
15N) and 40.16 (C1), 29.77 (C2), 20.42 (C3) and 13.95 ppm (CH3). The
15N signal is very close to that of 18HþClꢀ (ꢀ333.2) and in order to
explain such large effect, we decided to calculate the absolute
shieldings of butylammonium 4Hþ trifluoroacetate and hydro-
chloride salts (Fig. 2).
As it can be seen, the counteranion plays an important role and
satisfactorily explains the experimental results.
Concerning 13C chemical shifts, the effect on the methyl group is
about ꢀ2/ꢀ3 ppm save for methylamine (1, ꢀ3.9 ppm) and ethyl-
amine (2, ꢀ6.0 ppm). These values agree with previous results.23
3. Conclusions
For the first time a set of linear aliphatic amines, from C1 to C18,
has been studied experimentally by NMR, mainly 15N but also 13C,
and theoretically using DFT calculations. The conjunction of both
techniques is necessary to reach conclusions about the conforma-
tion of neutral amines (75% of Cs and 25% of C1 conformations), the
anomaly of the terminal methyl groups and the protonation effects.
GIAO theoretical calculations reproduce fairly well the influence of
the counteranion on the 15N chemical shifts of ammonium salts in
the solid state.
Average values for chain carbons are ꢀ1.2 (C1
a
carbon), ꢀ7.5 (C2
b
carbon) and ꢀ2.2 (C3
g carbon), the remaining carbons have al-
ways negative and small Dd values that are mainly due to solvent
effects (from CDCl3 to CF3CO2H), as were reported for other
amines.8,23,26 The signal of the methyl group in protonated amines,
about 11e12 ppm for most of them, is not explained by the GIAO
calculations where the effect of the protonation on the methyl
group is positive and almost negligible from 5 to 18 (ꢃ1 ppm).
2.5. NMR. Solid-state studies (CPMAS)
4. Experimental part
4.1. General
We have carried out a search in the Cambridge Structural Da-
tabase (CSD, refcodes)27 for the structure of ammonium salts from
14Hþ to 18Hþ (Table 5) excluding organometallic anions.
Melting points were determined under a microscope Axiolab
Zeiss with a TMS-92-Linkan heating stage and are uncorrected.
Samples of linear amines C3eC15 were purchased from Aldrich and
used without further purification: propylamine (bp 48 ꢁC), butyl-
amine (bp 78 ꢁC), amylamine (bp 104 ꢁC), hexylamine (bp
131e132 ꢁC), heptylamine (bp 154e156 ꢁC), octylamine (bp
175e177 ꢁC), nonylamine (bp 201 ꢁC), decylamine (mp 12e14 ꢁC),
undecylamine (mp 15e17 ꢁC), dodecylamine (mp 27e29 ꢁC), tri-
decylamine (mp 30e32 ꢁC), tetradecylamine (mp 38e40 ꢁC) and
pentadecylamine (mp 35e37 ꢁC).
Table 5
X-ray structures and refcodes27 of ammonium salts from 14Hþ to 18Hþ (no data
about 17Hþ). Rotation about the indicated bond (the rest all-trans)
Comp.
All-transa
Non all-trans structures
14
Anion: 4-bromocinnamate JEPZAG
Anion from a cholic acid,
XIQBAB
Anion: 1-carbocyclobutanecarboxylate
TOKVAR
Torsion in the middle,
between C4 and C5
15
16
Anion: 1-carbocyclobutanecarboxylate
TOKVEV
d
The ammonium trifluoroacetates 14Hþ, 15Hþ, 16Hþ and 18Hþ
were prepared by dissolving 300 mg of the amine in 2 mL of tri-
fluroacetic acid and then the excess of acid was evaporated at
normal pressure at þroom temperature: 14Hþ (mp 78e81 ꢁC), 15Hþ
(mp 81e82 ꢁC),16H (mp 85e86 ꢁC) and 18Hþ (mp 88e89 ꢁC). Two
hydrochlorides 4Hþ (mp 214 ꢁC, lit. Mp 214 ꢁC29) and 18Hþ (mp
161.5e162.5 ꢁC, lit. Mp 159e161 ꢁC30) were prepared by adding the
stoichiometric amount of aqueous hydrochloric acid (37%) to
a methanol solution of 4 and 18. Compound 18HþClL precipitated
from the solution as a crystalline solid and was used without fur-
ther purification. Compound 4HþClꢀ was obtained as a white solid
only after evaporation under reduced pressure of the methanolic
solution, redissolved again three times in methanol and the solvent
evaporated to dryness.
d
d
Anion from a cholic acid,
XIQBEF
Torsion in the middle,
between C4 and C5
18
Anion: diiodoplumbate,b
WOLPAP
Rotation about two bonds:
CeCeCeNH3
þ
a
The all-trans conformations are usually distorted in a kind of corkscrew.
No examples with a non organometallic anion.
b
None of the data involves trifluoroacetate or hydrochloride an-
ions, so we carried out crystallization experiments without suc-
ceeding in obtaining single crystals useful for X-ray determinations.
The data reported in Table 5 indicate that for the studied anions
both all-trans and rotated conformations in different parts of the
alkyl chain were found.
4.2. NMR
Ammonium trifluoroacetates 14Hþ, 15Hþ, 16Hþ and 18Hþ were
prepared by dissolving the amine in trifluroacetic acid and evapo-
rating the excess of acid; ammonium hydrochlorides 4Hþ and 18Hþ
Solution NMR spectra were recorded on a Bruker DRX 400 (9.4 T,
400.13 MHz for 1H, 100.62 MHz for 13C and 40.56 MHz for 15N)
spectrometer with a 5-mm inverse-detection H-X probe equipped

4638
D. Sanz et al. / Tetrahedron 67 (2011) 4633e4639
Table 6
15N and 13C NMR chemical shifts of neutral amines,a ammonium trifluoroacetates and Dd protonation effects in the solid state
Comp.
N
C1
C2
C3
C4
C5
C6
C7
C8
C9
C10
C11
C12
C13
C14
C15
C16
C17
C18
Neutral
14
15
ꢀ348.7 43.3 38.9 29.0 32.2 32.2 32.2 32.2 32.2 32.2 32.2 32.2 33.6 24.0 14.3 (Me)
ꢀ348.8 43.4 39.0 29.1 29.7 32.7 32.7 32.7 32.7 32.2 32.2 32.7 32.2 33.9 24.1
42.8
14.5 (Me)
14.0 (Me)
24.0
16b
18b
ꢀ347.7 43.4 39.0 29.0 32.2 32.2 32.2 32.2 32.2 32.2 32.2 32.2 32.2 32.2 33.7
14.4 (Me)
33.7
ꢀ347.8 43.4 39.0 29.2 32.2 32.2 32.2 32.2 32.2 32.2 32.2 32.2 32.2 32.2 32.2
32.2
24.0 14.4 (Me)
Cations
14Hþ
ꢀ343.9 39.8 30.6 28.4 28.9 33.0 33.0 33.0 33.0 33.0 33.0 33.0 34.5 24.7 13.9 (Me)
ꢀ345.0
27.7
24.2
15Hþ
ꢀ343.4 39.8 31.6 28.4 29.1 32.6 32.6 32.6 32.6 32.6 32.6 32.6 32.6 34.4 24.1
14.6 (Me)
14.2 (Me)
25.1
ꢀ345.1 27.6
16Hþ
ꢀ344.0 40.0 32.4 28.6 29.4 33.4 33.4 33.4 33.4 33.4 33.4 33.4 33.4 33.4 34.7
14.4 (Me)
14.1 (Me)
13.6 (Me)
34.6
ꢀ345.1 39.1
ꢀ345.9
27.8
24.4
18Hþ
ꢀ343.8 39.9 32.2 28.4 29.2 33.2 33.2 33.2 33.2 33.2 33.2 33.2 33.2 33.2 33.2
33.2
33.7
24.9 14.2 (Me)
13.8 (Me)
13.3 (Me)
24.9 15.3 (Me)
ꢀ345.0 38.8
ꢀ345.9
27.7
18Hþc ꢀ333.2 39.6 30.9 28.9 33.7 33.7 33.7 33.7 33.7 33.7 33.7 33.7 33.7 33.7 33.7
34.9
28.1
Protonation effectsd
14
15
16
18
18c
þ4.3 ꢀ3.5 ꢀ8.3 ꢀ1.0 ꢀ3.3 þ0.8 þ0.8 þ0.8 þ0.8 þ0.8 þ0.8 þ0.8 þ0.9 þ0.5 ꢀ0.4 (Me)
þ4.6 ꢀ3.3 ꢀ7.4 ꢀ1.1 ꢀ0.6 ꢀ0.1 ꢀ0.1 ꢀ0.1 ꢀ0.1 ꢀ0.1 ꢀ0.1 ꢀ0.1 þ0.4 þ0.5 0.0
þ2.7 ꢀ3.9 ꢀ6.6 ꢀ0.8 ꢀ2.8 þ1.2 þ1.2 þ1.2 þ1.2 þ1.2 þ1.2 þ1.2 þ1.2 þ1.2 þ1.0
þ2.9 ꢀ4.0 ꢀ6.8 ꢀ1.2 ꢀ3.0 þ1.0 þ1.0 þ1.0 þ1.0 þ1.0 þ1.0 þ1.0 þ1.0 þ1.0 þ1.0
þ14.6 ꢀ3.8 ꢀ8.1 ꢀ0.7 þ1.5 þ1.5 þ1.5 þ1.5 þ1.5 þ1.5 þ1.5 þ1.5 þ1.5 þ1.5 þ1.5
þ0.2 (Me)
þ0.8
ꢀ0.4 (Me)
þ0.9
þ1.0
þ0.9 ꢀ0.6 (Me)
þ0.9 þ0.9 (Me)
þ1.5
þ1.2
a
Amines 1e13 are or become liquids into the zirconia rotor at 298 K.
Values taken from Ref. 11.
Hydrochloride.
b
c
d
Dd
¼d
(ammonium cations)ꢀd(neutral amines), when several values were observed in the spectrum Dd has been calculated from the average value.
–344.0
–342.8
–333.5
O
Cl
CF3
H
H
H
Calcd.
Exp.
H3C
N
H3C
N
H3C
N
O
H
H
H
H
H
H
4H+ Cl
4H+
4H+ CF3CO2
–
–
–349.1
–332.6
Cl
H
H
H3C
N
H3C
N
H
H
H
H
4H+ (in CF3CO2H solution)
4H+ Cl (CPMAS)
–
Fig. 2. Protonation and phase effects in butylammonium salts.
with a z-gradient coil, at 300 K. Chemical shifts (
d
in ppm) are given
(gs-HMBC) and relaxation delay 1 s. The FIDs were processed using
zero filling in the F1 domain and a sine-bell window function in
both dimensions was applied prior to Fourier transformation. In the
gs-HMQC experiments GARP modulation of 13C was used for
decoupling. Selected parameters for (1He15N) gs-HMBC and
(1He15N) gs-HMQC spectra were spectral width 3500 Hz for 1H and
12.5 kHz for 15N, 1024ꢄ256 data set, number of scans 4, relaxation
delay 1 s, 37e60 ms delay for the evolution of the 15Ne1H long-
range coupling. The FIDs were processed using zero filling in the
F1 domain and a sine-bell window function in both dimensions was
applied prior to Fourier transformation.
from internal solvent, CDCl3 7.26 for 1H and 77.0 for 13C, and for 15
N
NMR nitromethane (0.00) was used as external standard. The
spectra done in TFA solution was recorded with a lock capillary with
DMSO-d6 2.49 for 1H and 39.5 for 13C. Typical parameters for 1H
NMR spectra were spectral width 3500 Hz and pulse width 7.5
an attenuation level of 0 dB. Typical parameters for 13C NMR
spectra were spectral width 7 kHz, pulse width 10.6 s at an at-
tenuation level of ꢀ6 dB and relaxation delay 2 s; WALTZ-16 was
used for broadband proton decoupling; the FIDS were multiplied by
an exponential weighting (lb¼2 Hz) before Fourier transformation.
2D inverse proton detected heteronuclear shift correlation spectra,
(1He13C) gs-HMQC, (1He13C) gs-HMBC, (1He15N) gs-HMQC,
(1He15N) gs-HMBC were acquired and processed using standard
Bruker NMR software and in non-phase sensitive mode. Gradient
selection was achieved through a 5% sine truncated shaped pulse
gradient of 1 ms. Selected parameters for (1He13C) gs-HMQC and
gs-HMBC spectra were spectral width 3500 Hz for 1H and 7000 Hz
for 13C, 1024ꢄ256 data set, number of scans 2 (gs-HMQC) or 4
ms at
m
Solid-state 13C (100.73 MHz) and 15N (40.60 MHz) CPMAS NMR
spectra have been obtained on a Bruker WB 400 spectrometer at
300 K using a 4 mm DVT probehead. Samples were carefully packed
in a 4-mm diameter cylindrical zirconia rotor with Kel-F end-caps.
Operating conditions involved 3.2 m
s 90ꢁ 1H pulses and decoupling
field strength of 78.1 kHz by TPPM sequence. 13C spectra were
originally referenced to a glycine sample and then the chemical
shifts were recalculated to the Me4Si [for the carbonyl atom

D. Sanz et al. / Tetrahedron 67 (2011) 4633e4639
4639
(glycine)¼176.1 ppm] and 15N spectra to 15NH4Cl and then con-
9. Balaban, A. T.;Dinculescu, A.;Elguero, J.;Faure, R. Magn. Reson. Chem.1985, 23, 553.
10. Alkorta, I.; Elguero, J. Magn. Reson. Chem. 2004, 42, 955.
d
verted to nitromethane scale using the relationship:
d
15N(MeNO2)¼
11. Sanz, D.; Claramunt, R. M.; Alkorta, I.; Elguero, J. J. Mol. Struct. 2010, 969, 106.
12. In this paper there was an error concerning the 15N chemical shifts of hex-
adecylamine (HDA, 16) and octadecylamine (ODA, 18); they were reported
at ꢀ330.0 ppm in CDCl3 while the correct value (see Table 2) is ꢀ357.5 ppm.
13. Faure, R.; Llinares, J.; Claramunt, R. M.; Elguero, J. Spectrosc. Int. J. 1983, 2, 381.
14. Elguero, J.; Faure, R.; Llinares, J. Spectrosc. Lett. 1987, 20, 149.
15. MacPhail, R. A.; Strauss, H. L.; Snyder, R. G.; Elliger, C. A. J. Phys. Chem.1984, 88, 334.
16. Boese, R.; Weiss, H. C.; Blaser, D. Angew. Chem., Int. Ed. 1999, 38, 988.
17. Kawata, M.; Ten-no, S.; Kato, S.; Hirata, F. J. Am. Chem. Soc. 1995, 117, 1638.
18. NIST ChemistryWebBook. Available from: http://webbook.nist.gov/chemistry.
19. Maksic, Z. B.; Vianello, R. J. Phys. Chem. A 2002, 106, 419.
d
15N(NH4Cl)ꢀ338.1 ppm. Typical acquisition parameters for 13C
CPMAS were: spectral width, 40 kHz; recycle delay, 5e15 s; acqui-
sition time, 30 ms; contact time, 2 ms; and spin rate,12 kHz. Typical
acquisition parameters for 15N CPMAS were: spectral width, 40 kHz;
recycle delay, 15 s; acquisition time, 30 ms; contact time, 2e5 ms;
and spin rate, 6 kHz.
4.3. Computational details
20. Raabe, G.; Wang, Y.; Feischhauer, J. Z. Naturforsch. 2000, 55a, 687.
21. Vianello, R.; Maskill, H.; Maksic, Z. B. Eur. J. Org. Chem. 2006, 2581.
22. Blanco, F.; Alkorta, I.; Elguero, J. Magn. Reson. Chem. 2007, 45, 797.
23. Llinares, J.; Elguero, J.; Faure, R.; Vincent, E.-J. Magn. Reson. Chem. 1980, 14, 20.
24. Duthaler, R. O.; Roberts, J. D. J. Am. Chem. Soc. 1998, 100, 3889.
Calculations were carried out at the B3LYP/6-31G
level31,32
*
using the Gaussian 03 programs.33 Frequency calculations at the
same level were carried out to verify that the structures correspond
to energy minima (no imaginary frequencies). A further geometry
optimization has been carried out at B3LYP/6-311þþG(d,p) com-
putational level. These geometries have been used for the calcula-
tions of the absolute chemical shieldings with the GIAO method34
at the same computational level. No other computational
methods were used since GIAO/B3LYP/6-311þþG(d,p) afforded
convenient results in previous works,22,25,35 but we are aware that
depending on the nucleus other possibilities could be preferable.36
ꢀ
25. Navarro, P.; Reviriego, F.; Alkorta, I.; Elguero, J.; Lopez, C.; Claramunt, R. M.;
~
García-Espana, E. Magn. Reson. Chem. 2006, 44, 1067.
26. Sarneski,J. E.;Surprenant,H. L.;Molen,F. K.;Reilley, C.N. Anal. Chem.1975, 47, 2116.
27. Cambridge Structural Database Allen, F. H. Acta Crystallogr., Sect. B 2002, 58,
380; Available from: Allen, F. H.; Motherwell, W. D. S. Acta Crystallogr., Sect. B
2002, 58, 407; http://www.ccdc.cam.ac.uk CSD version 5.31, updated Feb. 2010.
28. (a) Apperley, D. C.; Fletton, R. A.; Harris, R. K.; Lancaster, R. W.; Tavener, S.;
ꢀ
Threlfall, T. L. J. Pharm. Sci. 1999, 88, 1275; (b) Claramunt, R. M.; Escolastico, C.;
ꢀ
Elguero, J. Arkivoc 2001, i, 183; (c) Claramunt, R. M.; Lopez, C.; García, M. A.;
ꢀ
Otero, M. D.; Torres, M. R.; Pinilla, E.; Alarcon, S. H.; Alkorta, I.; Elguero, J. New J.
Chem. 2001, 25, 1061; (d) Portieri, A.; Harris, R. K.; Fletton, R. A.; Lancaster, R.
W.; Threlfall, T. L. Magn. Reson. Chem. 2004, 42, 313; (e) Santa María, M. D.;
Claramunt, R. M.; García, M. A.; Elguero, J. Tetrahedron 2007, 63, 3737.
29. Gamer, A. O.; Heliwig, J.; van Ravenzwaay, B. Food Chem. Toxicol. 2002, 40, 1833.
30. Chanley, J. D.; Kalichstein, S.; Gindler, E. M. J. Am. Chem. Soc. 1953, 75, 5133.
31. Becke, A. D. Phys. Rev. A 1988, 38, 3098; Becke, A. D. J. Chem. Phys. 1993, 98,
5648; Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
Acknowledgements
This work was carried out with financial support from the
Ministerio de Ciencia e Innovacion (CTQ2010-16122 and CTQ2009-
13129-C02-02) and Comunidad Autonoma de Madrid (Project
ꢀ
ꢀ
32. Hariharan, P. A.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213.
33. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz,
J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-
Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03;
Gaussian,: Pittsburgh, PA, 2003.
MADRISOLAR2, ref. S2009/PPQ-1533). Thanks are given to the CTI
(CSIC) for allocation of computer time.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.04.067.
References and notes
1. Elguero, J. An. Quim. 2005, 101, 31.
2. van Schaick, E. A.; Tukker, H. E.; Roelen, H. C. P. F.; Ijzerman, A. P.; Danhof, M. Br.
J. Pharmacol. 1998, 124, 607.
34. (a) Ditchfield, R. Mol. Phys.1974, 27, 789; (b) London, F. J. Phys. Radium 1937, 8, 397.
3. Song, M.; Clark, M. J. Chem. Inf. Model. 2006, 46, 392.
4. Stothers, J. B. Carbon-13 NMR Spectroscopy; Academic: New York, NY, 1972.
5. Breitmaier, E.; Voelter, W. 13C NMR Spectroscopy, 2nd ed.; Chemie: Weinheim,
1978; p 185.
6. Kalinowski, H. O.; Berger, S.; Braun, S. Carbon-13 NMR Spectroscopy; John Wiley
& Sons: Chichester, UK, 1988.
7. Berger, S.; Braun, S.; Kalinowski, H.-O. NMR Spectroscopy of the Non-Metallic
Elements; Wiley: Chichester, UK, 1997.
8. Faure, R.; Llinares, J.; Elguero, J. An. Quim. 1985, 81C, 167.
ꢀ
ꢀ
ꢀ
35. (a) Perez-Torralba, M.; Lopez, C.; Perez-Medina, C.; Claramunt, R. M.; Pinilla, E.;
Torres, M. R.; Alkorta, I.; Elguero, J. Cryst. Eng. Comm. 2010, 12, 4052; (b) Alkorta,
I.; Elguero, J. Magn. Reson. Chem. 2010, 48, S32; (c) Alkorta, I.; Elguero, J. Tet-
rahedron: Asymmetry 2010, 21, 437; (d) Ballesteros-Garrido, R.; Bonnafoux, L.;
Blanco, F.; Ballesteros, R.; Leroux, F. R.; Abarca, B.; Colobert, F.; Alkorta, I.; El-
guero, J. Dalton Trans. 2011, 40, 1387.
36. Pedone, A.; Pavone, M.; Menziani, M. C.; Barone, V. J. Chem. Theory Comput.
2008, 4, 2130.