Conformational analysis of 5-piperidinevaleric acid, 5-(N- methylpiperidine)valerate and their hydrogen halides by MO calculations, X- ray, diffraction and FTIR spectroscopy

Article abstract of DOI:10.1016/S0022-2860(98)00903-X

The most stable conformers of 5-(piperidine)valeric acid (1), 5-(N- methylpiperidine)valerate (2) and their hydrogen halides (3 and 4) were analyzed by the semiempirical PM3 method and selected compounds by the B3LYP/6-31G(d,p) method. As some of the investigated compounds are charged and the others can be neutral, some have acidic proton, others do not. They are capable of forming ionic bonds (via Coulombic attraction between the oppositely charged groups) or of forming the various types of hydrogen bonded conformers. As a result these compounds are ideally suited to study the importance of electrostatic interactions and hydrogen bonding on the relative stabilities of conformers. In the case of compounds containing N- methylpiperidine unit, for a particular conformer, the intramolecular attractive electrostatic interactions between the charged group play key roles in their relative stability in the gas phase. The electrostatic interaction of the X^- ion with the positively charged nitrogen atom decreases their proton-acceptor properties and COOH···X^- hydrogen bonds are present in all hydrogen halides (3). 5-Piperidine valeric acid with HF forms a molecular complex, while with HCl, HBr and HI an ion pair, according to the B3LYP calculations. The PM3 calculations predict a molecular complex also with HCl. The crystal structure of 5-(piperidine)valeric acid hydrogen bromide (4HBr), space group of crystals P2₁/n with a = 6.204(1), b = 32.777(7), c = 6.416(1) A, β = 106.21(3)°, Z = 4 and R = 0.0685 was characterized by X-ray crystallography methods. Br^- ion forms two types of hydrogen bonds: Br···N(1), 3.247(14) A, and O(1) ···Br, 3.118(11) A. Moreover, C-H···Br short contacts, which can be recognized as weak hydrogen bonds, exist in the crystal. The FTIR spectrum of 1 in the solid state shows an intense broad absorption in the 1600-400 cm^-1 region typical for a very short NHO hydrogen bonds. In solution the hydrogen bond seems to be longer. The bands of vC=O at 1708 cm^-1 and v(as)COO^- at 1615 cm^-1 in CD₃CN solution show that OH···N ? O^-···HN⁺ equilibrium exists. Ab initio calculations predict molecular structures of three most stable conformers of 1 in the gas phase.

Full text of DOI:10.1016/S0022-2860(98)00903-X

Journal of Molecular Structure 484 (1999) 125–138
Conformational analysis of 5-piperidinevaleric acid, 5-(N-
methylpiperidine)valerate and their hydrogen halides by MO
calculations, X-ray diffraction and FTIR spectroscopy
*
Mirosław Szafran , Zofia Dega-Szafran, Ewa Dulewicz, Zofia Kosturkiewicz,
Magdalena Nowakowska, Wioletta Orwat, Małgorzata Ratajczak-Sitarz
Faculty of Chemistry, Adam Mickiewicz University, ul Grunwaldzka 6, 60-780 Pozna n´ , Poland
Received 9 October 1998; accepted 16 November 1998
Abstract
The most stable conformers of 5-(piperidine)valeric acid (1), 5-(N-methylpiperidine)valerate (2) and their hydrogen halides
3 and 4) were analyzed by the semiempirical PM3 method and selected compounds by the B3LYP/6-31G(d,p) method. As
(
some of the investigated compounds are charged and the others can be neutral, some have acidic proton, others do not. They are
capable of forming ionic bonds (via Coulombic attraction between the oppositely charged groups) or of forming the various
types of hydrogen bonded conformers. As a result these compounds are ideally suited to study the importance of electrostatic
interactions and hydrogen bonding on the relative stabilities of conformers. In the case of compounds containing N-methylpi-
peridine unit, for a particular conformer, the intramolecular attractive electrostatic interactions between the charged group play
Ϫ
key roles in their relative stability in the gas phase. The electrostatic interaction of the X ion with the positively charged
Ϫ
…
nitrogen atom decreases their proton-acceptor properties and COOH
X
hydrogen bonds are present in all hydrogen halides
(
3). 5-Piperidine valeric acid with HF forms a molecular complex, while with HCl, HBr and HI an ion pair, according to the
B3LYP calculations. The PM3 calculations predict a molecular complex also with HCl. The crystal structure of 5-(piperi-
˚
dine)valeric acid hydrogen bromide (4HBr), space group of crystals P2 /n with a ˆ 6.204(1), b ˆ 32.777(7), c ˆ 6.416(1) A,
1
Ϫ
b ˆ 106.21(3)Њ, Z ˆ 4 and R ˆ 0.0685 was characterised by X-ray crystallography methods. Br ion forms two types of
…
˚
…
˚
…
hydrogen bonds: Br N(1), 3.247(14) A, and O(1) Br, 3.118(11) A. Moreover, C–H Br short contacts, which can be
recognized as weak hydrogen bonds, exist in the crystal. The FTIR spectrum of 1 in the solid state shows an intense broad
Ϫ1
absorption in the 1600–400 cm region typical for a very short NHO hydrogen bonds. In solution the hydrogen bond seems to
Ϫ1
Ϫ
Ϫ1
Ϫ
ϩ
…
…
HN
be longer. The bands of nCyO at 1708 cm and nasCOO at 1615 cm in CD
equilibrium exists. Ab initio calculations predict molecular structures of three most stable conformers of 1 in the gas phase.
1999 Elsevier Science B.V. All rights reserved.
3
CN solution show that OH N O O
᭧
Keywords: 5-(Piperidine)valeric acid; Conformation; PM3; B3LYP calculations; X-ray diffraction; FTIR
1
. Introduction
Theoretical calculations were used successfully to
analyze the relative energies and geometries of the
conformers of a fairly large number of amino acids
[1]. In the gas phase amino acids are known to exist as
*
Corresponding author. Tel.: ϩ48 61 869 9181; fax: ϩ48 61 865
008.
E-mail address: szafran@main.amu.edu.pl (M.P. Szafran)
8
0
022-2860/99/$ - see front matter ᭧ 1999 Elsevier Science B.V. All rights reserved.
PII: S0022-2860(98)00903-X

1
26
M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
their hydrogen halides (3 and 4) (Scheme 1) are
obtained from PM3, ab initio calculations and X-ray
diffraction. From these results, the influence of the
methylene groups separating the positively charged
nitrogen atom from the COO group, effects of electro-
static interactions, H-bonds and protonation on the
relative energies of the conformers are discussed.
Recently Feeder and Jones [27] have determined
the crystal structures of five v-phthalimidoalkanocar-
boxylic acids (C H O N– (CH ) COOH, n ˆ 1–5)
8
4
2
2 n
and demonstrated that hydrogen bonds vary with n .
Four v-piperidinealkanocarboxylic acid (C H N–
Scheme 1.
5
10
(
CH ) COOH, n ˆ 1–4) were investigated in solution
2
n
neutral molecules, while zwitterionic forms dominate
in crystalline or aqueous media [1–6]. For each
neutral and zwitterionic species these are a large
number of possible conformers. In the case of N,N-
dimethylglycine five of the most stable conformers
were analyzed by ab initio calculations [1]. Amino
acids form crystalline acid and alkaline salts,
however, they were much less systematic studied
by Zundel et al. [28–30] and intramolecular hydrogen
bonds were postulated.
2. Experimental
The general synthesis of N-(4-carboxybutyl)piper-
idinium bromide (4HBr) and its N-methyl derivative
(3HBr) is quaternization of piperidine or N-methylpi-
peridine with ethyl 5-bromovalerate, followed by acid
hydrolysis of ester function [31]. Piperidine (0.2 mol)
was mixed on cooling with ethyl 5-bromovalerate
(0.1 mol). The piperidine hydrobromide was filtered
off, and the ethyl 5-piperidinevalerate was heated with
15% HCl or 24% HBr for 8 h. After evaporation of the
acid and water under reduce pressure, the solid was
recrystallized from acetonitrile-methanol solution
[6]. It is concluded, that for a particular conformers
the relative strength and number of possible H-bonds
that can be formed and not necessarily the magnitude
ofthedipolemomentplaykeyrolesinrelativestabilityof
amino acid conformers in the gas phase. In the case of
zwitterionic species (amino acids and betaines) the
electrostaticcompensationofchargesbetweentheoppo-
sitely charged nitrogen atom and carboxylate group
and H-bonding determine their relative stability [7].
N-Alkylated amino acids play important role in a
biological chemistry [8–15]. The incorporation of N-
alkylated amino acids, in place of natural amino acids,
into proteins is known to have dramatic effects on the
bioactive conformation of such mutant proteins. The
study of the activity of such mutant proteins reveals
the importance of H-bonds on the activity of proteins
in general [16–25]. N-alkylation of amino acids is
known also to increase the population of the neutral
tautomers in solution [26]. Knowledge of the most
stable conformers of the individual N-alkylated
amino acids and the factors that contribute to their
stability is essential in order to understand fully the
biological consequences of their incorporation into
proteins.
(10 : 1).
chloride (5-piperidinevaleric acid hydrogen chloride)
(4HCl) m.p. 204ЊC–205ЊC. Analysis for
C H NClO : calculated: C, 54.17%; H, 9.09%; N,
The
N-(4-carboxybutyl)piperidinium,
1
0
20
2
6.32%; found C, 54.13%; H, 9.06% N, 6.35%;
4HBr, mp 202ЊC. Analysis for C H NBrO : calcu-
1
0
20
2
lated: C, 45.12%; H, 7.57%; N, 5.26%; found C,
45.10%; H, 7.62%; N, 5.19%. The 5-piperidinevaleric
acid (1) was obtained from the reaction of 4HCl with
K CO in small amount of water. After water evapora-
2
3
tion, the acid was extracted with chloroform and the
extract was dried over Na SO The solvent was
evaporated and the residue was stored over P O and
recrystallized from anhydrous acetonitrile, m.p. 79ЊC.
5-(N-Methylpiperidine)valerate (N-(4-carboxybutyl)-
N-methylpiperidinium inert salt, betaine) (2) and its
hydrobromides (3HBr) were prepared from N-
2
4.
2
5
In this article, the relative energies and optimized
geometries of the 5-piperidinevaleric acid (1), 5-(N-
methylpiperidine)valerate (piperidine betaine) (2) and
methylpiperidine
and
ethyl
5-bromovalerate

M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
127
Table 1
Table 3
2
3
Crystal data and structure of refinement for N-(4-carboxybutyl)pi-
peridinium bromide (4)
Anisotropic displacement parameters (A × 10 ) for N-(4-carbox-
ybutyl)piperidinium bromide (4). The anisotropic displacement
2
2
2
…
ϩ
factor exponent takes the form: Ϫ 2p [h a* U11
ϩ
Empirical formula
Formula weight
Temperature (K)
Wavelength (A)
Crystal system
Space group
10 2
C H20BrNO
266.18
293(2)
0.71073
Monoclinic
2
hka*b*U12]
U
11
U
22
U
33
U
23
U
13
U
12
˚
Br
50(1) 64(1)
40(4) 51(6)
57(7) 57(8)
63(8) 70(9)
49(1)
40(4)
73(8)
Ϫ 8(1)
Ϫ 9(4)
Ϫ 9(6)
6(1)
13(4)
6(1)
Ϫ 6(4)
33(6) Ϫ 11(6)
P2
1
/n
N(1)
C(2)
C(3)
Unit cell dimensions
˚
78(9) Ϫ 26(7)
23(7)
3(7)
15(7)
0(7)
a (A)
6.204(1)
32.775(7)
6.416(1)
106.21(3)
1252.7(4)
4
1.411
3.261
552
˚
C(4) 82(10) 55(9) 122(14)
C(5) 92(11) 65(9)
C(6)
C(7)
C(8)
C(9)
C(10) 83(9) 62(9)
C(11) 70(8) 56(8)
O(1) 102(7) 66(6) 102(8)
O(2) 122(9) 56(7) 156(11)
13(9) Ϫ 2(10)
b (A)
˚
67(8)
45(6)
54(7)
46(6)
51(7)
60(8)
49(7)
15(7)
9(6)
3(6)
3(5)
5(5)
3(6)
4(5)
4(6)
8(7)
16(8)
20(5)
23(6)
12(5)
22(6)
34(7)
25(6)
55(6)
86(9)
c (A)
65(7) 70(9)
62(7) 60(8)
51(6) 65(8)
77(8) 46(7)
Ϫ 7(6)
6(6)
b (deg)
Volume(A )
3
˚
Z
5(6)
9(6)
5(7)
8(6)
Ϫ3
Ϫ1
Density (calculated) (Mg m
Absorption coefficient (mm
F(000)
Crystal size (mm)
u range for data collection (deg) 1.24–27.06
)
)
0.10 × 0.22 × 0.45
11(6)
Ϫ 1(6)
Index ranges
Ϫ 7 Յ h Յ 7, 0 Յ k Յ 35, 0 Յ
Յ 8
1
Reflections collected
Independent reflections
Computer Programs
2861
according the procedure given in Ref. [31].
2646 [R(int) ˆ 0.1103]
Compound 2·H O was recrystallized from acetoni-
2
SHELXS-86[38] SHELXL-
trile, m.p. 210ЊC–213ЊC dec. 3HBr, m.p. 127–
130ЊC from acetonitrile. Analysis for C H NBrO :
9
3[39]
2
Refinement method
Full-matrix least-squares on F
2637/0/129
1.239
1
1
24
2
Data/restraints/parameters
calculated: C, 47.15%; H, 7.91%; N, 5.00%; found C,
2
Goodness-of-fit on F
4
7.14%; H, 7.92%; N, 4.92%.
Final R indices [I Ͼ 2s(I)]
R1 ˆ 0.0685, wR2 ˆ 0.2094
Structures and energies were calculated by means
Largest diff. peak and hole
0.945 and–1.142
Ϫ3
of the PM3 semiempirical method [32], as imple-
mented in the AMPAC 5.0 program package [33].
The ab initio calculations were performed with
GAUSSIAN 94 program package [34]. The B3LYP
exchange correlation functional [35,36] has been used
throughout. This consists of the Lee–Yang–Parr [35]
correlation functional in conjugation with a hybrid
exchange functional first proposed be Becke [36].
The split-valence polarized 6-31G(d,p) basis set [37]
˚
(
e A
)
Table 2
Atomic coordinates ( × 10 ) and equivalent isotropic displacement
4
2
3
˚
parameters (A
×
10 ) for N-(4-carboxybutyl)piperidinium
bromide (4). U(eq) is defined as one third of the trace of the ortho-
gonalized Uij tensor.
x
y
z
U
(eq)
Br
9068(2)
4902(15)
2954(20)
3143(23)
3388(28)
5377(26)
5149(22)
4700(20)
6668(20)
6564(22)
8398(24)
8401(23)
1502(1)
1396(3)
1549(4)
2008(4)
2235(5)
2078(4)
1622(4)
953(4)
748(4)
292(4)
68(4)
Ϫ 378(4)
Ϫ 536(3)
Ϫ 559(3)
7864(2)
56(1)
44(2)
59(3)
69(4)
93(5)
76(4)
59(3)
57(3)
55(3)
57(3)
65(3)
57(3)
85(3)
102(4)
was used. Relative energy (kcal/mol), E , was taken
rel
N(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
O(1)
O(2)
3517(14)
4210(22)
4614(24)
2724(31)
2048(24)
1573(19)
3157(20)
2595(19)
2827(20)
2125(21)
2321(19)
1836(18)
2809(22)
as the difference in molecular energy E between that
conformation and the minimum-energy conformation.
X-ray diffraction analysis was carried out using a
KUMA-4 diffractometer equipped with graphite
monochromator. The Br ion position was found
from the Patterson map, the remaining non-hydrogen
atoms from Fourier and difference Fourier syntheses.
The positions of hydrogen atoms are derived from
geometric conditions and refined as riding on the
heavier atoms. The crystal data and details concerning
data collection and structure refinement are given in
10118(18)
7016(22)

1
28
M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
Table 4
Heats of formation (kcal/mol), dipole moments and selected geometrical parameters for the various conformations of 5-piperidinevaleric acid
a
and its derivatives calculated by the PM3 method
…
N
…
…
…
1…
1…
…
H X
DH
E
rel
m
O
1
N
X
N
H
H
X
Ͻ NHX
O
X
O
H
1
Ͻ O HX
1
1
1
2
2
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
ft
ec
et
f1
f2
e
Ϫ 122.1
Ϫ 123.3
Ϫ 121.3
Ϫ 68.98
Ϫ 74.11
Ϫ 37.91
Ϫ 136.6
Ϫ 143.8
Ϫ 131.1
Ϫ 133.7
Ϫ 131.1
Ϫ 128.8
Ϫ 133.4
Ϫ 122.6
Ϫ 126.6
Ϫ 124.0
Ϫ 119.0
Ϫ 123.2
Ϫ 114.9
Ϫ 117.0
Ϫ 114.3
Ϫ 106.6
Ϫ 111.1
Ϫ 106.5
Ϫ 109.6
Ϫ 106.9
Ϫ 193.4
Ϫ 188.6
Ϫ 191.5
Ϫ 191.7
Ϫ 189.4
Ϫ 152.2
Ϫ 148.6
Ϫ 151.5
Ϫ 151.6
Ϫ 149.2
Ϫ 137.8
Ϫ 131.5
Ϫ 132.6
Ϫ 133.7
Ϫ 130.9
Ϫ 116.6
Ϫ 117.6
Ϫ 119.1
Ϫ 118.7
Ϫ 115.9
1.2
0
2
6.23 2.785
1.26 7.138
4.05 6.891
Ϫ
1.818
Ϫ
Ϫ
Ϫ
Ϫ
0.971
0.952
0.949
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
5.1 15.39 3.477
14.24 3.067
Ϫ
Ϫ
0
Ϫ
Ϫ
Ϫ
36.2 31.17 6.756
7.2 14.81 5.313
0
12.7
10.1
12.7 11.08 6.906
4.6 15.09 5.435
0
Ϫ
Ϫ
Ϫ
ft1HF
ft2HF
ec1HF
ec2HF
et HF
ft1HCl
ft2HCl
ec1HCl
ec2HCl
etHCl
ft1HBr
ft2HBr
ec1HBr
ec2HBr
etHBr
ft1HI
ft2HI
ec1HF
ec2HI
etHI
3.422
2.843
2.794
2.817
2.815
3.561
3.156
2.991
2.976
2.997
3.621
3.187
2.980
2.976
2.974
4.266
3.987
3.745
3.949
3.944
2.740
2.760
2.760
2.762
2.763
3.020
3.040
3.041
3.044
3.046
2.826
2.826
2.827
2.825
2.826
3.003
2.895
2.898
2.979
2.975
Ϫ
Ϫ
2.623
2.636
6.727
7.349
7.217
2.782
2.783
6.758
7.401
7.264
3.529
3.544
6.794
7.401
7.255
3.795
3.939
6.463
7.784
7.380
2.719
8.093
6.648
8.878
8.863
3.624
8.376
6.878
9.140
9.110
3.540
8.240
7.080
9.114
9.130
3.896
7.923
6.420
8.996
8.785
0.977
0.976
0.952
0.952
0.949
0.983
0.983
0.952
0.952
0.949
0.955
0.983
0.952
0.952
0.949
0.956
0.956
0.952
0.952
0.953
0.963
0.953
0.952
0.952
0.949
0.973
0.953
0.952
0.952
0.949
0.954
0.953
0.953
0.952
0.949
0.955
0.953
0.953
0.952
0.949
1.659 168.1
1.661 176.8
7.413
8.006
6.968
1.811 168.5
1.803 174.0
7.429
8.052
7.016
2.612 161.0
2.612 165.4
7.465
8.052
6.985
2.877 161.2
3.008 176.8
7.062
8.378
6.793
13.60 4.928
8.38 7.075
9.43 6.851
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
14.92 5.237
9.55 7.082
Ϫ
Ϫ
10.8
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
6.8 10.31 6.830
9.4 11.89 6.901
4.2 13.67 5.578
0
8.3
6.2 11.04 6.830
8.9 12.56 6.899
4.5 16.93 5.547
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
14.19 5.701
9.86 7.082
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
0
18.38 6.044
Ϫ
Ϫ
4.6 14.40 7.105
1.5 17.63 6.773
4.2 17.84 6.704
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
ftHF
0
7.94 4.733
1.93 3.844
3.67 4.699
3.65 6.917
4.31 6.945
9.35 4.927
3.31 3.844
4.89 4.643
4.77 6.916
4.83 6.949
12.58 5.135
8.48 3.848
1.784
1.803
1.802
1.805
1.806
1.677
1.716
1.715
1.721
1.723
1.111
1.133
1.133
1.139
1.141
1.074
1.066
1.063
1.083
1.083
0.966
0.958
0.958
0.957
0.957
1.351
1.326
1.326
1.324
1.323
1.721
1.701
1.701
1.697
1.695
1.941
1.960
1.971
1.909
1.908
169.8
178.7
178.8
179.7
179.8
171.9
179.1
179.2
177.3
177.8
170.7
171.3
172.0
169.8
170.1
169.0
144.5
143.9
168.8
167.7
2.454 172.8
fc1HF
fc2HF
ecHF
etHF
4.8
1.9
1.7
4
7.108
8.673
9.857
8.403
1.851 175.9
7.370
8.892
10.110
8.647
2.590 173.9
7.151
9.134
10.110
8.690
Ϫ
Ϫ
Ϫ
Ϫ
ftHCl
fc1HCl
fc2HCl
ecHCl
etHCl
ftHBr
fc1HBr
fc2HBr
ecHBr
etHBr
ftHI
0
3.6
0.7
0.6
3
0
6.3
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
5.2 10.09 4.372
4.1
6.9
2.5 13.98 5.332
1.5 10.38 3.878
0
9.44 6.911
8.37 6.981
2.943 175.5
fc1HI
fc2HI
ecHI
7.275
8.428
9.004
8.299
Ϫ
Ϫ
Ϫ
Ϫ
11.98 3.855
0.4 11.62 7.036
3.2 10.89 6.967
etHI
a
2 4
Abbreviations. e: extended (trans-zig–zag) and f: folded (gauche) conformation on the N(CH ) COO moiety, respectively; c: cis and t: trans
arrangement of the CyO/OH bonds, respectively.

M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
129
Table 5
Selected dihedral angles for the various conformations of 5-piperidinevaleric acid and its derivatives calculated by the PM3 method
a
O
2
C
11
O
1
H
N
1
C
7
C
8
C
9
C
7
C
8
C
9
C
10
C
8
C
9
C
10
C
11
C
9
C
10
C
11
O
1
C
10
C
11
C
12
O
2
1 7 8
MeN C C
1
1
1
2
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
ft
ec
et
f1
Ϫ 177.5
Ϫ 0.14
Ϫ 178.9
Ϫ
77.9
Ϫ 93.3
108.9
Ϫ 67.0
114.0
63.6
109.0
Ϫ
Ϫ 173.9
Ϫ 174.4
119.9
130.8
140.3
143.5
Ϫ 168.0
179.9
Ϫ 178.5
141.5
151.9
Ϫ 178.9
Ϫ 179.4
Ϫ 75.2
Ϫ 74.8
Ϫ 136.4
Ϫ 79.2
179.5
Ϫ 178.1
Ϫ 179.9
Ϫ 56.2
84.8
Ϫ 64.6
134.7
Ϫ 175.7
178.6
Ϫ 178.7
Ϫ 66.1
139.1
175.3
178.5
Ϫ 178.6
Ϫ 67.1
150.0
175.2
178.5
Ϫ 177.8
Ϫ 78.7
161.6
173.5
178.3
171.2
Ϫ 165.2
Ϫ 172.5
Ϫ 177.8
Ϫ 177.5
Ϫ 67.3
Ϫ 76.8
Ϫ 178.2
Ϫ 178.7
Ϫ 67.3
Ϫ 76.4
Ϫ 178.0
Ϫ 178.6
Ϫ 67.6
Ϫ 73.1
Ϫ 177.3
Ϫ 176.4
Ϫ 68.8
Ϫ 64.0
Ϫ 177.7
Ϫ 175.2
Ϫ 113.7
Ϫ 71.5
89.1
Ϫ 66.2
95.5
Ϫ 92.6
106.3
Ϫ 78.3
Ϫ 65.1
98.4
Ϫ 97.0
106.7
Ϫ 75.6
Ϫ 64.1
99.2
Ϫ 100.2
106.8
Ϫ 75.6
Ϫ 62.6
100.6
Ϫ 133.2
105.7
Ϫ 68.5
Ϫ 30.8
44.7
70.3
67.9
64.8
102.4
Ϫ 92.2
Ϫ 102.4
Ϫ 71.1
101.7
Ϫ 97.7
Ϫ 102.3
Ϫ 71.5
97.4
Ϫ 96.2
Ϫ 102.9
Ϫ 73.1
94.8
Ϫ 98.9
Ϫ 94.7
Ϫ 71.9
Ϫ
Ϫ
Ϫ 89.5
113.9
Ϫ 85.2
87.4
Ϫ 74.2
102.3
116.4
Ϫ 82.7
82.9
Ϫ 73.9
105.2
117.5
Ϫ 80.8
79.2
Ϫ 73.7
105.2
119.2
Ϫ 79.0
47.3
Ϫ 75.2
112.7
151.9
Ϫ 137.2
Ϫ 110.7
Ϫ 113.2
Ϫ 116.4
Ϫ 77.8
87.9
160.9
Ϫ 172.9
175.9
Ϫ 173.4
Ϫ 60.2
Ϫ 179.8
Ϫ 179.7
175.1
176.4
Ϫ 59.9
Ϫ 178.5
Ϫ 179.2
175.2
174.8
Ϫ 60.1
Ϫ 178.5
Ϫ 178.2
178.7
179.7
Ϫ 57.4
Ϫ 178.8
Ϫ 178.9
Ϫ
f2
Ϫ
ft1HF
ft2HF
ec1HF
ec2HF
etHF
174.4
Ϫ 179.1
1.51
Ϫ 1.33
Ϫ 178.3
173.7
Ϫ 179.9
1.71
Ϫ 1.50
Ϫ 178.2
178.1
178.7
1.74
Ϫ 1.50
Ϫ 178.0
176.4
Ϫ 178.4
2.84
Ϫ 1.96
Ϫ 176.1
176.1
179.5
Ϫ 179.2
Ϫ 139.4
Ϫ 83.2
179.6
Ϫ 179.4
Ϫ 178.8
Ϫ 160.9
Ϫ 86.4
Ϫ 179.9
Ϫ 179.4
Ϫ 177.8
169.9
Ϫ 68.8
179.2
Ϫ 177.7
Ϫ 177.6
64.0
ft1HCl
ft2HCl
ec1HCl
ec2HCl
etHCl
ft1HBr
ft2HBr
ec1HBr
ec2HBr
etHBr
ft1HI
ft2HI
ec1HI
ec2HI
etHI
Ϫ 168.0
Ϫ 179.1
Ϫ 178.6
145.7
161.2
Ϫ 167.3
Ϫ 179.1
Ϫ 177.4
Ϫ 179.8
159.1
Ϫ 173.0
Ϫ 179.3
Ϫ 177.0
73.1
73.5
76.4
84.8
126.3
ftHF
ftHCl
ftHBr
ftHI
fc1HF
fc2HF
ecHF
etHF
fc1HCl
fc2HCl
ecHCl
etHCl
fc1HBr
fc2HBr
ecHBr
etHBr
fc1HI
fc2HI
ecHI
177.8
177.6
177.3
56.0
56.3
60.6
Ϫ
b
Ϫ 61.9
Ϫ 64.8
Ϫ
b
Ϫ 0.47
Ϫ 0.22
Ϫ 0.35
Ϫ 178.9
Ϫ 0.75
Ϫ 0.03
Ϫ 0.32
Ϫ 178.8
Ϫ 1.89
0.18
Ϫ 0.15
Ϫ 179.2
Ϫ 1.95
0.34
Ϫ 0.50
Ϫ 178.9
Ϫ 71.9
Ϫ 64.7
Ϫ 178.2
Ϫ 178.2
Ϫ 72.1
Ϫ 64.5
Ϫ 178.0
Ϫ 177.9
Ϫ 73.2
Ϫ 76.6
Ϫ 177.3
Ϫ 176.9
Ϫ 73.8
Ϫ 70.5
Ϫ 178.9
Ϫ 177.2
163.6
Ϫ
Ϫ 166.1
Ϫ 165.9
126.6
77.8
Ϫ
109.5
Ϫ 78.5
82.4
Ϫ
Ϫ
162.3
Ϫ
Ϫ 165.9
Ϫ 165.6
127.7
77.8
Ϫ
109.1
Ϫ 82.5
83.8
Ϫ
b
b
b
b
b
b
b
b
166.4
165.7
177.3
177.6
170.7
170.9
Ϫ 179.7
Ϫ 179.2
132.7
Ϫ 165.6
Ϫ 164.7
127.7
127.3
Ϫ 179.6
Ϫ 178.7
77.2
107.3
Ϫ 85.1
81.2
85.4
108.7
etHI
a
2 4
Abbreviations. e: extended (trans-zig–zag) and f: folded (gauche) conformation on the N(CH ) COO moiety, respectively; c: cis and t: trans
arrangement of the CyO/OH bonds, respectively.
b
1 7 8
HN C C

1
30
M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
Fig. 1. Optimized PM3 structures for three most stable conformers
of 5-piperidinevaleric acid (1).
Table 1. The atomic coordinates, equivalent aniso-
tropic displacement parameters are presented in
Tables 2 and 3, respectively.
Ϫ1
The FTIR spectra were measured at 2 cm resolu-
tion using a Bruker IFS 113v instrument, which was
evacuated to avoid water and CO absorptions. Each
2
spectrum consists of 250 scans at ca. 30ЊC. The solid
Fig. 3. Optimized PM3 structures for the most stable conformers of
N(4-carboxybutyl)-N-methyl-piperidinium fluoride and bromide
spectra were measured in Nujol and Fluorolube. The
Ϫ3
solution spectra (0.3 mol dm in CHCl and satu-
3
(
3).
Ϫ3
rated solution (ca. 0.2 mol dm ) in CH CN) were
3
measured in cell with KBr windows, 0.22 mm thick.
Samples were prepared in a dry box.
the PM3 optimized conformers. Selected data
obtained from the B3LYP/6-31G(d,p) calculations
are given in Table 6.
3. Results and discussion
3
.1. Conformers of 5-piperidinevaleric acid (1)
Table 4 shows heats of formation, relative energies,
From Table 4 it is apparent that according to the
dipole moments and selected hydrogen bond distances
calculated by the semiempirical PM3 method, for the
most stable conformations of 5-piperidinevaleric acid
(1), and 5-(N-methylpiperidine)valerate (2) and their
hydrogen halides (3 and 4). Dihedral angles for the
flexible N-CH CH CH CH COO moiety are collected
2
2
2
2
in Table 5. In folded conformers dihedral angles are in
range between gauche and eclipsed. Figs. 1–4 show
Fig. 2. Optimized PM3 structures for two most stable conformers of
Fig. 4. Optimized PM3 conformers of N-(4-carboxybutyl)piperi-
dine hydrogen fluoride and bromide (4).
5
-(N-methylpiperidine)valerate (2).

M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
131
m

1
32
M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
semiempirical PM3 data, conformer 1ec (extended
without hydrogen bond, with the trans-zig–zag
conformation of N–CH CH CH CH COOH moiety,
compensation would be replaced by intermolecular
one.
2
2
2
2
3
.3. Conformers of N-(4-carboxybutyl)-N-
and the cis arrangement of the CyO/OH bonds) is
Ϫ1
methylpiperidinium halides (3)
ca. 1.2 kcal mol more stable than conformer 1ft
(
folded with intramolecular hydrogen bond and
trans CyO/OH bonds). However, conformer 1et
with trans arrangement of the CyO/OH bonds) is
Five conformers, 3ft1HX, 3ft2HX, 3ec1HX
ec2HX, and 3etHX could be located at the PM3
3
(
Ϫ1
calculations. Conformers 3ft1HX and 3ft2HX can
be derived by addition of HX to 2f1 and 2f2, respec-
tively. Analogous to 2, conformers 3ft2HX are more
stable than 3ft1HX. These conformers are stabilized
less stable than 1ft by ca. 0.8 kcal mol . The
B3LYP method predicts opposite stability trend; 1ft
has the lowest energy (Table 6). The trans arrange-
ment of the CyO/OH bonds in 1ft and 1et contributes
to the magnitude of the dipole moment and lowering
stability. Similar observation were made for different
orientations of the CyO/OH bonds in N, N-dimethyl-
glycine [1] and formic acid [40].
The small energy difference between 1ft and 1ec
suggests that the energy of the intramolecular
hydrogen bond in 1ft is comparable with the energy
difference between trans and gauche of the N–
CH CH CH CH COOH moiety and between cis–
ϩ
by the Coulombic attraction between the N atom and
Ϫ
X
ion, and additionally by the hydrogen bonds
Ϫ
between the X ion and HOOC group. Extended
conformers without hydrogen bonds, 3ec1HX,
3
ec2HX, and 3etHX, are less stable than the folded.
…
The N X distances in 3ft2HX are slightly longer
than these in 3etHX. These differences indicate that
Ϫ
hydrogen bonding between OH and X decreases
Ϫ
electrostatic interaction of the X anion with the posi-
2
2
2
2
tive charged nitrogen atom. However, the electrostatiϪc
interaction decreases proton acceptor property of X
anions and in consequence the proton is closer the
oxygen atom.
trans of the CyO/OH bonds in 1ec.
3
.2. Conformers of 5-(N-methylpiperidine)
valerate(2)
3
.4. Conformers of N-(4-carboxybutyl)piperidinium
According to the results listed in Tables 4 and 5 two
folded conformers are formed, 2f1 and 2f2 (Fig. 2).
Both conformers are stabilized by the intramolecular
Coulombic attraction between the positively charged
nitrogen atom and the negatively charged oxygen
halides (4)
So, far 5-piperidinevaleric acid (1) was treated as
alkylated amino acid. However, (1) can also be
considered as tertiary amine with COOH as a substi-
tuent.
Ϫ
atoms of the COO group. Similar folding of the
carboxybutyl unit was observed in the pyridine
IR spectra of strongly hydrogen-bonded complexes
between ammonia and amines (methylamine,
dimethylamine and trimethylamine) and hydrogen
halides were measured in the gas phase, argon and
nitrogen matrices [44]. In those complexes the extent
of the proton transfer increases from HF through to
HI, with increasing base strength and with increasing
betaine [7]. Conformer 2f2 is more stable than 2f1
Ϫ1
by 5 kcal mol and has lower dipole moment and
similar molar volume (Table 4). Extended conformer
Ϫ1
(
2e) is less stable by 36 kcal mol than 2f2. This
suggests that the attractive coulombic energy is
much larger than the energy difference between
trans and gauche conformations of methylene groups
…
…
polarity of the matrix. The N
H
X stretching mode
ϩ
Ϫ
in the N –CH CH CH CH COO moiety. In general,
which passes through a minimum at methylamine-
2
2
2
2
molecules with smaller dipole moments are favored in
the gas phase [41–43]. Conformation of the investi-
gated compound in a crystal would be significantly
different from these in the gas phase. Methylene
units in the tether would have trans-zig–zag confor-
mation and would be arranged antiparallel as in pyri-
dine betaines [7]; the intramolecular charge
Table 7
Ϫ1
Cis–trans energy difference for COOH group (kcal mol
)
Method
1
4HF
4HCl
4HBr
4HI
B3LYP
PM3
5.8
2.0
2.3
2.4
2.8
2.8

M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
133
Table 8
Bond lengths (A), bond angles and dehedral angles (deg) for 5-piperidinevaleric acid and its hydrogen halides.
˚
Method
X-ray
HF
B3LYP
B3LYP
B3LYP
B3LYP
B3LYP
Compound
4ecHBr
4ftHBr
4ftHF
4ftHCl
3ftHF
1ft
1ec
Bond lengths
N(1)– C(7)
N(1)– C(2)
N(1)– C(6)
C(2)– C(3)
C(3)– C(4)
C(4)– C(5)
C(5)– C(6)
C(7)– C(8)
C(8)– C(9)
C(9)– C(10)
C(10)– C(11)
C(11)– O(2)
C(11)– O(1)
O(1)– H
1.470(14)
1.4957
1.4753
1.5075
1.5402
1.4753
1.4632
1.4661
1.4663
1.5315
1.5336
1.5331
1.5318
1.5333
1.5330
1.5289
1.5125
1.2173
1.3558
0.9722
1.487(14)
1.495(14)
1.53(2)
1.47(2)
1.51(2)
1.53(2)
1.52(2)
1.50(2)
1.52(2)
1.47(2)
1.16(2)
1.30(2)
1.10(3)
0.91(3)
1.4921
1.4977
1.5251
1.5273
1.5276
1.5241
1.5286
1.5335
1.5370
1.5185
1.1878
1.3189
0.9545
1.0379
5.2532
3.1831
3.4175
1.4892
1.4870
1.5307
1.5343
1.5340
1.4863
1.5356
1.5371
1.5414
1.5281
1.2102
1.3449
0.9845
1.4405
4.6309
2.4759
2.6809
1.5021
1.5087
1.5293
1.5333
1.5333
1.5278
1.5313
1.5375
1.5409
1.5290
1.2115
1.3410
0.9876
1.0918
5.0666
2.2945
3.1547
1.5297
1.5291
1.5293
1.5358
1.5354
1.5291
1.5316
2.5540
1.5453
1.5363
1.2191
1.3255
1.0436
1.4814
1.4778
1.5310
1.5337
1.5334
1.5311
1.5345
1.5415
1.5566
1.5296
1.2117
1.3416
1.0076
1.7058
2.706
N(1)– H
Ϫ
Ϫ
…
N(1) O(1)
Ϫ
Ϫ
5.067
Ϫ
…
…
N(1)
O(1)
X
X
3.247(11)
3.188(11)
Ϫ
3.2655
2.4371
1.4982
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
…
Me N(1)
Ϫ
Ϫ
Ϫ
Bond angles
C(7)– N(1)– C(2)
C(7)– N(1)– C(6)
C(2)– N(1)– C(6)
N(1)– C(2)– C(3)
C(4)– C(3)– C(2)
C(3)– C(4)– C(5)
C(4)– C(5)– C(6)
N(1)– C(6)– C(5)
N(1)– C(7)– C(8)
C(9)– C(8)– C(7)
C(10)– C(9)– C(8)
C(11)– C(10)– C(9)
O(2)– C(11)– O(1)
O(2)– C(11)– C(10)
O(1)– C(11)– C(10)
C(11)– O(1)–H
109.9(8)
112.5(9)
111.3(9)
110.7(9)
112.3(12)
110.4(12)
110.7(13)
110.2(10)
115.7(10)
110.8(10)
113.2(11)
116.0(11)
125.5(13)
123.4(13)
111.1(12)
109.5
114.12
109.62
111.65
111.11
111.51
109.74
111.46
112.13
116.54
117.48
113.79
110.47
121.30
122.01
116.65
114.03
108.12
107.42
105.39
171.23
174.73
104.17
Ϫ
110.22
112.68
110.24
111.30
111.04
109.96
111.21
110.90
115.53
115.89
114.33
111.52
121.47
123.19
115.32
111.31
111.31
103.56
106.19
Ϫ
114.11
109.86
111.29
111.13
111.60
109.79
111.48
111.85
116.24
117.01
114.12
110.78
121.38
122.40
116.18
112.54
108.07
108.15
104.89
171.84
177.96
Ϫ
109.93
110.46
112.54
110.23
111.60
111.21
110.03
111.04
111.24
115.91
117.32
117.30
114.87
122.38
121.48
116.14
112.40
107.50
107.50
113.73
Ϫ
111.70
112.71
110.79
111.25
110.92
110.01
110.00
111.29
113.63
112.18
112.56
113.22
122.35
126.17
111.48
105.94
Ϫ
110.62
108.51
112.41
110.46
110.32
110.31
112.47
116.99
116.22
114.14
111.66
123.00
120.93
116.04
112.41
Ϫ
C(7)– N(1)– H
C(2)– N(1)– H
C(6)– N(1)– H
N(1)– H–X
107.6
107.6
107.6
170.6(3)
164.1(3)
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
O(1)– H–X
Ϫ
Ϫ
Ϫ
Ϫ
O(1)H–Br–H(N1)
C(2)– N(1)– Me
C(6)– N(1)– Me
C(7)– N(1)– Me
Torsial angles
109.77
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
110.51
110.92
106.34
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
C(4)– C(5)– C(6)– N(1)
C(4)– C(3)– C(2)– N(1)
C(5)– C(6)– N(1)– C(7)
C(6)– N(1)– C(7)– C(8)
Ϫ 57.26(15)
Ϫ 55.44(15)
179.38(10)
59.62(13)
54.53
Ϫ 56.72
177.4
Ϫ 57.22
56.69
Ϫ 177.03
62.94
55.17
Ϫ 56.60
177.01
Ϫ 57.75
57.28
177.21
Ϫ 54.88
Ϫ 57.32
56.04
Ϫ 176.60
69.24
Ϫ 56.40
56.66
Ϫ 174.31
73.38
179.04
176.53

1
34
M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
Table 8 (continued)
Method
X-ray
HF
B3LYP
B3LYP
B3LYP
B3LYP
B3LYP
Compound
4ecHBr
4ftHBr
4ftHF
4ftHCl
3ftHF
1ft
1ec
N(1)– C(7)– C(8)– C(9)
C(7)– C(8)– C(9)– C(10)
C(8)– C(9)– C(10)– C(11)
C(9)– C10)– C(11)– O(1)
C(9)– C(10)– C(11)– O(2)
C(10)– C(11)– O(1)– H
O(2)– C(11)– O(1)– H
C(6)– N(1)– H–X
165.47(10)
61.45
52.77
60.91
94.79
69.95
173.99
175.78(10)
179.68(11)
Ϫ 175.33(11)
5.95(20)
179.97(14)
Ϫ 1.35(2.2)
Ϫ 171.7
51.6
62.39
169.66
77.71
Ϫ 100.03
4.97
Ϫ 177.28
Ϫ 18.76
100.41
Ϫ
58.20
183.12
71.23
Ϫ 107.18
3.41
Ϫ 178.14
63.33
Ϫ 57.81
Ϫ 52.16
Ϫ
63.62
177.07
76.49
Ϫ 101.13
4.53
Ϫ 177.83
4.85
123.69
61.09
Ϫ
Ϫ 133.37
Ϫ 54.68
95.85
Ϫ 82.24
Ϫ 3.31
174.74
Ϫ
Ϫ 80.54
108.28
115.39
Ϫ 63.89
Ϫ 3.43
Ϫ 182.72
Ϫ
179.77
179.20
179.00
Ϫ 1.09
179.83
Ϫ 0.08
Ϫ
C(2)– N(1)– H–X
Ϫ
Ϫ
Ϫ
C(5)– C(6)– N(1)– H
C(3)– C(2)– N(1)– Me
C(5)– C(6)– N(1)– Me
61.03(14)
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
65.56
Ϫ 65.04
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Fig. 5. X-ray molecular structure and atomic numbering of N-(4-carboxybutyl)piperidinium bromide (4HBr). The thermal ellipoids were drawn
at the 50% probability level.
hydrogen chloride or ammonia-hydrogen bromide in
argon matrix (but at ammonia-hydrogen chloride in
nitrogen matrix), then increases as to extent of the
proton transfer to the nitrogen increases [45]. Barnes
and Legon [44] from the nitrogen nuclear quadrupole
coupling constants, x(N)/MHz, estimated in the gas
phase the following percentage of ionic character of
hydrogen bromide are shown in Fig. 4. According to
the PM3 data in complexes with HF and HCl proton is
closer to halide atom (a molecular complex), whereas
in the case of HBr and HI proton is transferred to the
nitrogen atom (an ion pair) (Table 4). The B3LYP
calculations gave slightly different results, which are
in excellent agreement to the experimental results of
Me N–HX complexes: 12% (HF), 60% (HCl), 83%
complexes of Me N with HX in the gas phase [44].
3
3
(
HBr), and 100% (HI). Golubev and Denisov [46]
Thus no proton transfer take place in 4ftHF while in
4ftHCl, 4ftHBr and 4ftHI complexes proton is trans-
ferred from these hydrogen halides to the 5-piperidi-
nevaleric acid (Table 8).
In 4ftHX conformers two hydrogen bonds, NHX
and OHX, are present. Generally formation of the
second hydrogen bonds elongate the first one. This
trend was observed in the 1 : 1 and 2 : 1 complexes
of pentachlorophenol with pyridine N-oxides [47]. In
studied the complexes of trimethylamine with
hydrogen chloride and hydrogen bromide in the gas
phase by NMR specrtroscopy and reported that a
strongly hydrogen bonds complex was formed with
hydrogen chloride whereas the complex with
hydrogen bromide was close to an ion pair.
The most stable conformers of complexes of 5-
piperidinevaleric acid with hydrogen fluoride and

M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
135
Fig. 6. Molecular packing in the unit cell at N-(4-carboxybutyl)piperidinium bromide (4HBr).
…
˚
4
ftHI the N X distance is ca. 0.1 A longer than these
pirical data are ca. three time lower but are close to the
experimental data for formic acid [49].
with one hydrogen bond. However, this rule is broken
in complexes with HF, HCl and HBr. Formation of
OHX hydrogen bonds shortening the NHX one by ca.
3
.6. X-ray structure of N-(4-
˚
carboxybutyl)piperidinium bromide (4HBr)
0
.02 A.
Considering hydrogen iodides the most stable is
conformer 4fc2HI and the less stable is conformer
Perspective drawing of the complex of 5-(piperidi-
ne)valeric acid with hydrogen bromide (4HBr) and
numbering scheme of its atoms are shown in Fig. 5.
The piperidine ring adopts the usual chair conforma-
4
I
etHI. Conformer 4fc2HI is stabilized by the
Ϫ
ϩ
…
HN hydrogen bond and the electrostatic inter-
ϩ
action between the N atom and the oxygen atom of
COO group. Conformer 4fc2HI is very similar to
conformer 2f1. The longer O N distance in
conformer 4fc2HI (ca. 0.4 A) than in conformer 2f1,
Ϫ
tion with the (CH ) –COOH chain at the equatorial
2 4
position and the proton at the axial position as it is
seen from Fig. 5. Geometrical parameters are
collected in Table 8. The asymmetry parameters of
the chair conformation are equal 0.4 [50]. The angle
between the best plane of hydrocarbon chain and
C(2)C(3)C(5)C(6) ring atoms is 26.5(6)Њ. The
carboxyl group is twisted relative to the carbon
chain by 6.6(2)Њ. The carboxyl group has a cis
arrangement and forms H-bond with the bromide
…
˚
suggests that the positively charged nitrogen atom
in the former compound is mainly neutralized by
Ϫ
I
ion via hydrogen bond. In complexes with HF,
HCl and HBr the electrostatic interaction between
ϩ
the N atom and the oxygen atom (4fc1HX and
4
fc2HX) are weaker as the most stable conformers
are 4ftHX.
…
˚
…
ion; O Br is 3.188(20) A and ЄO–H Br is 164Њ.
Ϫ
The Br ion forms also H-bond with the N–H proton;
Br N is 3.247(14) A and Є Br H–N is 170Њ (Fig.
). The DHA parameters are 22 and 19, respectively
…
˚
…
3
.5. Conformation of COOH group
6
for NHBr and OHBr hydrogen bonds [51]. This indi-
cates that NHBr bond is stronger than OHBr. The
Carboxylic acids may have their hydroxyl proton
either cis (syn) or trans (anti) to the CyO bond for
which we use the description c or t, respectively. Ab
initio calculation with 4-31G(d) basis set predicted
that c rotamer of formic acid is 6.2 kcal mol Ϫ 1
more stable than t [48]. The experimental values are
…
˚
intermolecular N Br distance is 4.364 A (sym.
…
code: 1 ϩ x, y, 1 ϩ z) and O Br distance is
˚
3
.201 A (sym. code: 2.5 ϩ x, 0.5 ϩ y, 1 ϩ z). As
Fig. 6 shows that contribution of the bromide ion to
stabilization the crystal structure is significant.
Ϫ1
in the range of 2–4 kcal mol [48]. Table 7 lists
calculated cis–trans energy difference for 1 and 4.
Value obtained by the B3LYP method is in good
agreement with datum for formic acid. The semiem-
3
.7. FTIR spectra
The FTIR spectra of powdered and solution

1
36
M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
3
Fig. 7. FTIR spectra in Nujol and Fluorolube mulls (—) and CHCl solution (…) of (a) 5-(piperidine)valeric acid (1), (b) N-(4-carboxybu-
tyl)piperidinium bromide (4HBr), (c) 5-(N-methylpiperidine)valerate (2), (d) N-(4-carboxybutyl)-N-methyl-piperidinium bromide (3HBr).
samples of the investigated compounds at room
temperature are shown in Fig. 7. The most striking
feature of the solid state spectrum of 1 is presence
spectroscopic data are typical for short hydrogen
…
˚
bonds, O N distance close to 2.5 A with nearly
symmetric location of the H-atom [52,53]. In solution
the broad absorption is shifted slightly toward higher
wavenumber. The spectrum of 1 in CHCl3 in
general is very similar to that in Ref. [28] and
suggests that hydrogen bond in solution is slightly
of a very broad and intense absorption below
Ϫ1
1
600 cm (Fig. 7a). Another interesting feature is
Ϫ1
intense band at 1650 cm . This band is in the middle
between the nCyO band at 1727 cm in the complex
Ϫ1
of 5-piperidinevaleric acid with hydrogen bromide
longer than that in the solid state. In CD CN
3
Ϫ
Ϫ1
Ϫ
(
4HBr) (Fig. 7b) and the n COO at 1569 cm in
solution two bands due to the nCyO and n COO
as
as
Ϫ1
Ϫ1
5-(N-methylpiperidine)valerate (2) (Fig. 7c). These
vibrations at 1709 cm and 1615 cm , respectively,

M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
137
3 3
Fig. 8. FTIR spectra of 5-piperidinevaleric acid in CD CN (—) and CHCl (…).
Ϫ… ϩ
Ϫ
…
proving OH N N O
HN prototropic equi-
decreases proton acceptor properties of the X ions
and in consequence the proton is closer to the oxygen
atom.
librium. In CHCl3 solution the nCyO vibration
Ϫ1
appears as a shoulder at ca. 1710 cm , but the
Ϫ1
nasCOO band at 1613 cm
is very strong. This
Complexes of 4HX are the most complicated
system, owing to protonation problem. The extent of
proton transfer in all 4HX, predicted by the B3LYP
calculations, is quite similar to that found in the gas
suggests that an ionic pair is the dominant species in
CHCl solution (Fig. 8). The spectra of hydrogen
bromides 4 and 3 show a broad absorption in the
3
Ϫ1
3
200–2200 cm region (Fig. 7b and d), typical for
phase in Me N·HX [44]. Thus no proton transfer take
3
˚
hydrogen bond longer then 3 A [54]. This absorption
in Fig. 7b is because of nNH and nOH vibration,
while in Fig. 7c to the nOH.
place in 4HF, while in 4HCl, 4HBr and 4HI the
proton from XH is transferred to the nitrogen atom.
According to the PM3 data 4HCl exists as a molecular
complex. In the case of complex with HF, HCl and
HBr the most stable is 4ftHX conformer, stabilized by
two hydrogen bonds, NHX and the OHX. Considering
complex with HI, the most stable is conformer
HN hydrogen bonϩd
and the electrostatic interactions between the N
atom and OyC bond.
4
. Conclusions
Ϫ
…
The PM3 semiempirical calculations were carried
4fc2HI, stabilized by the I
out on the most stable conformers of 1, 2 and their
hydrogen halides 3 and 4. Selected compounds were
analyzed by the B3LYP/6-31G(d,p) method.
The relative stabilities of three conformers of 1 vary
with the calculation methods. According to the
The 4HBr complex in the crystal has an extended
Ϫ
Ϫ
…
HN and
structure. The Br
Br
ion forms Br
Ϫ
…
HOOC hydrogen bonds with two molecules of
…
B3LYP data 1ft form with intramolecular N HO
protonated 5-(piperidine)valeric acid.
hydrogen bond has the lowest energy. The most stable
conformers of dimethylglycine is also stabilized by
similar intramolecular N HO bond.
The FTIR spectrum of 1 in the solid state shows an
intense broad absorption in the 1600–400 cm
Ϫ1
…
region typical for a very short NHO hydrogen bond.
In solution the hydrogen bond seems to be longer. The
Owing to the Coulombic interaction between the
positively charged nitrogen atom and the negatively
charged COO group of 2, from two folded conformers
Ϫ
ϩ
…
…
HN prototropic equilibrium is
OH N O O
present in CD CN solution.
3
…
O
2f2 has lower dipole moment and shorter N
distance, and is the most stable.
From five conformers of 3HX, the most stable are
conformers derived from 2f2 by addition of HX. The
most stable conformers have 3ft2HX form and are
stabilized by the Coulombic attraction between the
Acknowledgements
This work was supported by the Polish State
Committee of Scientific Research (KBN), grant 3
TO9A 09414. The ab initio calculations were carried
out at the Poznan Supercomputing Network Centre.
ϩ
Ϫ
Ϫ
…
X
N
atom and X ions, and by the COOH
hydrogen bond. The electrostatic interaction

1
38
M.P. Szafran et al. / Journal of Molecular Structure 484 (1999) 125–138
[28] B. Brzezinski, G. Zundel, Chem. Phys. Lett. 44 (1976) 521.
References
[
[
29] B. Brzezinski, G. Zundel, J. Magn. Res. 48 (1982) 361.
30] R. Kr a¨ mer, R. Lang, B. Brzezinski, G. Zundel, J. Chem. Soc.
Faraday Trans. 86 (1990) 627.
[
[
[
[
[
[
[
1] A.D. Headly, S.D. Starnes, J. Mol. Struct. (Theochem) 370
1996) 147.
2] J.H. Jensen, M.S. Gordon, J. Am. Chem. Soc. 113 (1991)
917.
3] F.R. Tortonda, J.L. Pascual-Ahuir, E. Silla, I. Tun o´ n, Chem.
Phys. Lett. 260 (1996) 21.
(
[31] Z. Dega-Szafran, R. Przybylak, J. Mol. Struct. 436/437 (1997)
107.
7
[
[
[
32] J.J.P. Stewart, J. Comput. Chem. 10 (1989) 221.
33] AMPAC 5.0, Semichem, Shawnee, KS 66216, 1994.
34] M.J. Frisch, G.W. Truck, M. Head-Gordon, P.M.W. Gill,
M.W. Wong, J.B. Foresman, B.G. Johnson, H.B. Schlegel,
M.A. Replogle, R. Gomperts, J.L. Andres, K. Rafhavachari,
J.S. Binkley, C. Gonzales, R.L. Martin, D.J. Fox, D.J. Defrees,
J. Baker, J.J.P. Stewart, J.A. Pople, GAUSSIAN 94, Revision
B. Gaussian Inc., Pittsburg, PA, 1994.
4] Y. Ding, K. Krogh-Jespersen, J. Comput. Chem. 17 (1996)
3
38.
5] O. Kikuchi, T. Watanabe, Y. Ogawa, H. Takase, O. Taka-
hashi, J. Phys. Org. Chem. 10 (1997) 145.
6] M.T. Rosado, M. Leonor, T.S. Duarte, R. Fausto, Vibrat.
Spectrosc. 16 (1998) 35.
7] M. Szafran, Z. Dega-Szafran, A. Katrusiak, G. Buczak, T.
Głowiak, J. Sitkowski, L. Stefaniak, J. Org. Chem. 63
[
[
[
[
35] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785.
36] A.D. Becke, J. Chem. Phys. 98 (1993) 5648.
37] P.C. Hariharan, J.A. Pople, Theor. Chim. Acta 28 (1973) 213.
38] G.M. Sheldrick, SHELXS-86. Program for the Solution of
Crystal Structures, University of Gottingen, Germany, 1986.
39] G.M. Sheldrick, SHELXL-93. Program for the Refinement of
Crystal Structures, University of Gottingen, Germany, 1993.
40] C.-H. Hu, M. Shen, H.F. Schaefer III, J. Am. Chem. Soc. 115
(1998) 2898.
[8] A. White, P. Handler, E.L. Smith, Principles of Biochemistry,
McGraw-Hill, New York, 1968.
[
[
[
[9] E.A. Bell, Febs. Lett. 64 (1976) 29.
[
[
[
[
[
[
10] N. Mandawa, J.D. Anderson, S.R. Dutky, Photochemistry 13
(1974) 2853.
(
1993) 2923.
41] H. Wennerst o¨ rm, F. Fors e´ n, B. Roos, J. Phys. Chem. 76 (1972)
430.
11] G. Boulvin, R. Ottinger, M. Pais, G. Chiurdoglu, Bull. Soc.
Chim. Belg. 78 (1970) 583.
12] W.D. Raverty, R.H. Thomson, T.J. King, J. Chem. Soc. Perkin
Trans. 1 (1977) 1204.
13] E. Schr o¨ der, K. L u¨ bke, The Peptides, II, Academic Press, New
York, 1966 pp. 397–423.
14] S.-G. Ang, M.P. Williamson, D.H. Williams, J. Chem. Soc.
Perkin Trans. 1 (1988) 1949.
2
[
[
42] X. Wang, K.N. Houk, J. Am. Chem. Soc. 110 (1988) 1870.
43] K.B. Wiberg, K.E. Laidig, J. Am. Chem. Soc. 110 (1988)
1872.
[
[
[
[
[
[
[
[
44] A.J. Barnes, A.C. Legon, J. Mol. Struct. 448 (1998) 101, and
references cited therein.
45] A. J. Barnes, M.P. Wrigth, J. Chem. Soc. Farady Trans. 2 82
15] J. Hlavacek, I. Fric, M. Budesinsky, K. Blah a´ , Collec. Czech.
Chem. Commun. 53 (1988) 2473.
(
1986) 153.
46] N.S. Golubev, G.S. Denisov, Chem. Phys. (USSR) (1982)
63.
[16] S.T. Cheung, N.L. Benoiton, Can. J. Chem. 55 (1977) 916.
[17] J. Konnert, I.L. Karle, J. Am. Chem. Soc. 91 (1969) 4888.
[18] V.F. Bystrov, S.L. Portnova, V.I. Tsetlin, V.T. Ivanov, Y.A.
Ovchinnikov, Tetrahedron 25 (1969) 493.
5
47] Z. Dega-Szafran, Z. Kosturkiewicz, E. Tykarska, M. Szafran,
D. Lema n˜ sky, B. Nogaj, J. Mol. Struct. 404 (1997) 25.
48] E.A. Hillenbrand, S. Scheiner, J. Am. Chem. Soc. 108 (1986)
[19] E. Fenude, L. Tomasic, G.P. Lorenzi, Biopolymers 28 (1989)
7
178.
49] M.R. Peterson, I.G. Csizmadia, J. Am. Chem. Soc. 101 (1979)
076.
1
85.
20] J. Dale, P. Groth, K. Titlestad, Acta Chem. Scand. B 31 (1977)
23.
[
1
5
50] W.L. Duax, D.A. Norrton, Atlas of Steroid Structures, Plenum
Press, New York, 1975 pp. 16–22.
51] M. Jask o´ lski, Preceedings, Fourth Symposium on Organic
Crystal Chemistry, A. Mickiewicz University, Pozna n´ 1988,
p. 222.
[
[
21] F.A. Bovey, J.J. Ryan, F.P. Hood, Macromolec. 1 (1968) 305.
22] S. Campbell, E.M. Marzluff, M.T. Rodgers, J.L. Beauchamp,
E.M. Rempe, K.F. Schwinck, D.L. Lichtenberger, J. Am.
Chem. Soc. 116 (1994) 5257.
[23] D. Choquet, H. Korn, Neuroscience Lett. 84 (1988) 329.
[24] M. Sandberg, I. Jacobson, J. Neurochem. 37 (1981) 1353.
[25] J.R. Cooper, F.E. Bloom, R.H. Roth, The Biochemical Basis
of Neuropharmacology, Oxford University Press, Oxford, UK,
[
[
[
52] B. Nogaj, E. Dulewicz, B. Brycki, A. Hrynio, P. Barczy n´ ski,
Z. Dega-Szafran, M. Szafran, P. Koziol, A.R. Katritzky, J.
Phys. Chem. 94 (1990) 1279.
53] Z. Dega-Szafran, M. Gdaniec, M. Grundwald-Wyspia n´ ska, Z.
Kosturkiewicz, J. Koput, P. Krzyzanowski, M. Szafran, J.
Mol. Struct. 270 (1992) 99.
1
991 pp. 48–75..
26] A.D. Headley, S.D. Starnes, J. Am. Chem. Soc. 117 (1995)
309.
27] N. Feeder, W. Jones, Acta Cryst. C 52 (1996) 913.
[
[
9
54] A. Novak, Struct. Bonding 18 (1974) 177.