Hydrogen bonds in 1:1 complex of piperidine-3-carboxylic acid with salicylic acid

Article abstract of DOI:10.1016/j.molstruc.2008.10.022

The 1:1 complex between the zwitterionic piperidinium-3-carboxylate (P3C) and salicylic acid (SAL), P3C·SAL, has been characterized by single crystal X-ray analysis, FTIR and NMR spectroscopy, and by DFT calculations. The crystals are orthorhombic, space

Full text of DOI:10.1016/j.molstruc.2008.10.022

Journal of Molecular Structure 920 (2009) 68–74
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Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Hydrogen bonds in 1:1 complex of piperidine-3-carboxylic acid with salicylic acid
a
a,
a
a,b
*
_
Elzbieta Bartoszak-Adamska , Zofia Dega-Szafran , Magdalena Krociak , Mariusz Jaskolski
,
Mirosław Szafran a
a Faculty of Chemistry, Adam Mickiewicz University, 60-780 Poznan´, Poland
b Center for Biocrystallographic Research, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan´, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
The 1:1 complex between the zwitterionic piperidinium-3-carboxylate (P3C) and salicylic acid (SAL),
P3CꢀSAL, has been characterized by single crystal X-ray analysis, FTIR and NMR spectroscopy, and by
DFT calculations. The crystals are orthorhombic, space group Pbca, with a = 11.6477(7), b = 9.1754(6),
c = 23.5833(12) Å. An OAHꢀ ꢀ ꢀO bridge (2.537(1) Å) links the SAL and P3C moieties. The proton in this
H bond is located closer to the salicylic carboxylate group. In the P3C moiety, the piperidine ring adopts
the chair conformation, and the carboxylate group is in the axial orientation and is stabilized by an intra-
molecular N+AHꢀ ꢀ ꢀO hydrogen bond of 2.847(1) Å. In the crystal packing, two P3CꢀSAL units form a cen-
trosymmetric dimer through a pair of intermolecular N+AHꢀ ꢀ ꢀO bonds of 2.801(1) Å. The dimers form a
zigzag chain linked via another N+AHꢀ ꢀ ꢀO bond (2.799(1) Å). In the structures of the monomeric
[P3CꢀSAL] and dimeric [(P3CꢀSAL)2] species optimized by B3LYP/6-31G(d,p) calculations, both the inter-
and intra-molecular hydrogen bonds are shorter than in the crystal. The FTIR spectrum shows a broad
Received 25 September 2008
Accepted 17 October 2008
Available online 1 November 2008
Dedicated to Professor Zofia Kosturkiewicz
on the occasion of her 80th birthday
Keywords:
Piperidine-3-carboxylic acid
Salicylic acid
Hydrogen bonds
X-ray diffraction
FTIR and NMR spectra
DFT calculations
absorption in the 3100–2400 cmꢁ1 region attributed to
mNH and mOH vibrations. The broad absorption
in the 1500–600 cmꢁ1 region is attributed to the OAHꢀO hydrogen bonds. The 1H and 13C NMR spectra
have been analyzed to elucidate the structure of the P3CꢀSAL complex in solution. The GIAO magnetic iso-
tropic shielding tensors have been used to predict the 1H and 13C chemical shifts in DMSO solution.
Ó 2009 Published by Elsevier B.V.
1. Introduction
2. Experimental
Piperidine-3-carboxylic acid, P3C, (nipecotic acid) is used as a
drug intermediate and also in the synthesis of -aminobutyric
(+/ꢁ) Piperidine-3-carboxylic acid and salicylic acid were pur-
chased from Aldrich Chemical Company. The P3CꢀSAL complex
was prepared by mixing of stoichiometric amounts of P3C dis-
solved in water and SAL dissolved in methanol. The precipitate
was recrystallized from water, m.p. 164 °C. The deuterated sample
was prepared by threefold recrystallization from D2O.
c
acid (GABA) uptake inhibitors [1]. P3C is a zwitterionic b-amino
acid and has two interacting centers, the proton-donor N+H2
group and the proton-acceptor COOꢁ group with the dissociation
constants of 10.20 and 3.45, respectively [2]. In the crystals of P3C
and its hydrochloride, the carboxylic group is in the equatorial
position [3,4], while in the complex with 4-hydroxybenzoic acid
(HBA) it is axial [5]. In view of the importance of both P3C and
salicylic acid (SAL) as building blocks in many compounds of
pharmaceutical interest [6–9], the present paper reports the crys-
tal structure of the 1:1 complex between piperidine-3-carboxylic
acid and salicylic acid, its spectroscopic properties as well as the
structures optimized by the B3LYP/6-31G(d,p) level of theory.
Recently, we have studied the effect of the hydroxyl group as
an additional substituent in proton-donor molecules in complexes
of P3C with HBA [5] and of N-methylmorpholine betaine (MMB)
with SAL [10].
Crystals of P3CꢀSAL for X-ray diffraction experiments were
grown from water. X-ray diffraction measurements were carried
out using graphite-monochromated Mo K
CCD diffractometer [11] equipped with an Oxford Instruments
low-temperature device. 612 scans were recorded in six orienta-
a radiation and a KM4-
x
tions of the crystal with 0.75° oscillation and an exposure time of
8 s. Integrated intensities were obtained using the CrysAlis pro-
gram [12]. The data set consisted of 16,034 observations which
were reduced in the mmm Laue class to 2573 unique data with
Rint = 0.0178. The structure was solved by direct methods with
SHELXS-97 and refined by full-matrix least squares minimization
P
2
of
wðF2o ꢁ F2c Þ using SHELXL-97 [13]. All hydrogen atoms were
derived from a difference Fourier map and included in the refine-
ment with isotropic B factors. The crystal data and details of data
processing are given in Table 1 and the atomic fractional coordi-
nates are in Table 2. The atom numbering system is shown in
* Corresponding author. Tel.: +48 61 8291216; fax: +48 61 8291505.
E-mail address: degasz@amu.edu.pl (Z. Dega-Szafran).
0022-2860/$ - see front matter Ó 2009 Published by Elsevier B.V.
doi:10.1016/j.molstruc.2008.10.022

E. Bartoszak-Adamska et al. / Journal of Molecular Structure 920 (2009) 68–74
69
Table 1
Table 2
Crystal data and structure refinement for the complex of piperidine-3-carboxylic acid
with salicylic acid.
Fractional atomic coordinates (ꢂ104) and equivalent isotropic displacement param-
eters (Å2 ꢂ 103) for the complex of piperidine-3-carboxylic acid with salicylic acid.
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
C13H17NO5
267.28
100
0.71073
Orthorhombic
Pbca
Atom
x
y
z
aUeq/Uiso
N(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
O(1)
5283(1)
4602(1)
3372(1)
2805(1)
3548(1)
4756(1)
3331(1)
2373(1)
4203(1)
1427(1)
2417(1)
595(1)
2849(1)
1732(1)
2237(1)
2715(1)
3810(1)
3232(1)
3463(1)
3656(1)
4210(1)
6190(1)
5545(1)
5924(1)
7282(1)
8140(1)
9169(1)
9323(1)
8473(1)
7472(1)
8015(1)
3686(18)
2487(17)
845(16)
1542(15)
1442(16)
1854(16)
3135(16)
4720(17)
4008(15)
2363(16)
3962(15)
9746(16)
10043(16)
8572(16)
6904(15)
4810(20)
7280(20)
5567(1)
5251(1)
5142(1)
5703(1)
6027(1)
6126(1)
4702(1)
4446(1)
4623(1)
3606(1)
3661(1)
3919(1)
3144(1)
3094(1)
2660(1)
2272(1)
2312(1)
2748(1)
3462(1)
5358(6)
5619(6)
5488(6)
4891(6)
4985(6)
5940(6)
5618(6)
5805(6)
6401(7)
6354(6)
6298(6)
2634(6)
1966(6)
2039(6)
2793(6)
3981(8)
3712(8)
17(1)
20(1)
17(1)
21(1)
20(1)
18(1)
15(1)
20(1)
23(1)
16(1)
21(1)
21(1)
15(1)
17(1)
20(1)
20(1)
21(1)
18(1)
24(1)
26(4)
28(4)
24(4)
23(3)
23(3)
24(4)
28(4)
23(3)
26(4)
20(3)
17(3)
23(3)
26(4)
25(4)
20(3)
59(5)
51(5)
Unit cell dimensions
a (Å)
b (Å)
11.6477(7)
9.1754(6)
23.5833(12)
2520.4(3)
8
1.409
0.109
1136
c (Å)
O(2)
C(10)
O(3)
Volume (Å3)
Z
Calculated density (g cmꢁ3
)
O(4)
Absorption coefficient (mmꢁ1)
F(000)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
O(5)
1339(1)
341(1)
248(1)
Crystal size (mm)
h range for data collection (°)
Limiting indices
0.55 ꢂ 0.52 ꢂ 0.24
4.14–26.37
1131(1)
2121(1)
2225(1)
ꢁ549(1)
5324(12)
6024(13)
4603(12)
5001(12)
2946(12)
2692(12)
2032(13)
3603(12)
3203(12)
4756(12)
5242(11)
ꢁ423(12)
1062(12)
2704(12)
2909(12)
2386(16)
ꢁ321(16)
ꢁ14 6 h 6 12
ꢁ11 6 k 6 11
ꢁ29 6 l 6 29
16034/2573 [Rint = 0.0178]
99.6
0.9744 and 0.9427
Full-matrix least-squares on F2
2573/0/241
H(1A)b
H(1E)
H(2A)
H(2E)
H(3E)
H(4A)
H(4E)
H(5A)
H(5E)
H(6A)
H(6E)
H(13)
H(14)
H(15)
H(16)
H(30)
H(50)
Reflections collected/unique
Completeness to h = 26.37° (%)
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
1.048
Final R indices [I > 2
R indices (all data)
r(I)]
R1 = 0.0292, wR2 = 0.0757
R1 = 0.0356, wR2 = 0.0812
0.0033(5)
0.328 and ꢁ0.179
Extinction coefficient
Largest diff. peak and hole (e Aꢁ3
)
Fig. 1. Molecular illustrations were prepared using ORTEPII [14]
and the XP package [15]. Atomic parameters in the CIF format
are available as Electronic Supplementary Publication from Cam-
bridge Crystallographic Data Centre (CCDC 703319).
FTIR spectra were measured on a Bruker IFS 66v/S instrument,
evacuated to avoid water and CO2 absorption, in Nujol and Fluorol-
ube suspensions using KBr plates. Each spectrum consisted of 64
scans.
a
Ueq is defined as one third of the trace of the orthogonalized Uij tensor.
A, axial; E, equatorial.
b
tensors were calculated by the standard GIAO/B3LYP/6-31G(d,p)
(Gauge-Independent Atomic Orbital) approach using the conduc-
tor-like screening continuum solvation model (COSMO) and the
geometries listed in Table 2.
NMR spectra were recorded on a Varian Gemini 300 VT spec-
trometer operating at 300.07 and 75.46 MHz for 1H and 13C,
respectively, and on a Bruker Advance DRX spectrometer operating
at 600.31 MHz for 1H. The spectra were measured in DMSO-d6 rel-
ative to TMS as internal reference. 2D (COSY, HETCOR) spectra
were obtained with standard Varian software.
3. Results and discussion
The DFT calculations were performed with the GAUSSIAN-03
program package [16]. The calculations employed the B3LYP
exchange-correlation functional, which combines the hybrid ex-
change functional of Becke [17,18] with the gradient-correlation
functional of Lee, Yang and Parr [19] and the split-valence polar-
ized 6-31G(d,p) basis set [20]. The magnetic isotropic shielding
3.1. Crystal structure
Fig. 1 presents the molecular structure and atomic numbering
of the P3CꢀSAL complex. The bond lengths, bond angles and se-
lected torsion angles are given in Table 3. P3CꢀSAL crystallizes in
Fig. 1. An ORTEP plot of the 1:1 complex of piperidine-3-carboxylic acid with salicylic acid. Anisotropic displacement ellipsoids have been drawn at the 50% probability level.
H atoms are represented as spheres of arbitrary radius. Dash lines indicate hydrogen bonds.

70
E. Bartoszak-Adamska et al. / Journal of Molecular Structure 920 (2009) 68–74
Table 3
Table 4
Experimental and B3LYP/6-31G(d,p)-calculated bond lengths (Å), and bond and
Geometry of the hydrogen bonds (Å and °) for the complex of piperidine-3-carboxylic
torsion angles (°) for the complex of piperidine-3-carboxylic acid with salicylic acid.
acid with salicylic acid.
X-ray
B3LYP/6-31G(d,p)
DAHꢀ ꢀ ꢀA
DAH
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
<DHA
P3CꢀSAL
(P3CꢀSAL)2
X-ray
N(1)AH(1A)ꢀ ꢀ ꢀO(2)a
N(1)AH(1E)ꢀ ꢀ ꢀO(1)b
N(1)AH(1A)ꢀ ꢀ ꢀO(2)
O(3)AH(30)ꢀ ꢀ ꢀO(1)
O(5)AH(50)ꢀ ꢀ ꢀO(4)
C(2)AH(2A)ꢀ ꢀ ꢀO(4)b
C(2)AH(2E)ꢀ ꢀ ꢀO(4)c
C(15)AH(15)ꢀ ꢀ ꢀO(5)d
0.91(2)
0.93(2)
0.91(2)
1.01(2)
0.93(2)
0.99(1)
0.98(2)
0.94(2)
2.01(2)
1.90(2)
2.22(2)
1.52(2)
1.71(2)
2.43(1)
2.46(1)
2.41(2)
2.801(1)
2.799(1)
2.847(1)
2.537(1)
2.573(1)
3.332(1)
3.236(1)
3.298(2)
144(1)
162(1)
125(1)
177(2)
152(2)
151(1)
135(1)
158(1)
Bond lengths
N(1)AC(2)
C(2)AC(3)
C(3)AC(4)
C(4)AC(5)
C(5)AC(6)
N(1)AC(6)
C(3)AC(7)
C(7)AO(1)
C(7)AO(2)
C(10)AC(11)
C(11)AC(12)
C(12)AC(13)
C(13)AC(14)
C(14)AC(15)
C(15)AC(16)
C(16)AC(11)
C(10)AO(3)
C(10)AO(4)
C(12)AO(5)
1.495(2)
1.476
1.538
1.553
1.537
1.533
1.478
1.529
1.225
1.327
1.474
1.419
1.405
1.387
1.403
1.387
1.407
1.324
1.243
1.433
1.503
1.531
1.539
1.536
1.529
1.496
1.549
1.262
1.263
1.478
1.420
1.405
1.387
1.404
1.387
1.407
1.328
1.240
1.341
1.528(2)
1.542(2)
1.530(2)
1.522(2)
1.496(2)
1.531(2)
1.281(1)
1.239(1)
1.485(2)
1.409(2)
1.398(2)
1.384(2)
1.395(2)
1.384(2)
1.402(2)
1.303(1)
1.242(1)
1.356(1)
B3LYP/6-31G(d,p)
P3CꢀSAL
O(3)AHꢀ ꢀ ꢀO(1)
O(2)AHꢀ ꢀ ꢀN(1)
O(5)AHꢀ ꢀ ꢀO(4)
(P3CꢀSAL)2
0.999
1.009
0.992
1.675
1.719
1.680
2.671
2.654
2.582
174.04
152.27
149.21
O(3)AHꢀ ꢀ ꢀO(1)
O(5)AHꢀ ꢀ ꢀO(4)
N(1)AH(1A)ꢀ ꢀ ꢀO(2)a
N(1)AH(1E)ꢀ ꢀ ꢀO(3)a
1.069
0.993
1.094
1.029
1.418
1.677
1.513
2.005
2.487
2.579
2.604
2.882
176.96
148.84
174.18
141.40
Symmetry codes: (a) ꢁx + 1, ꢁy + 1, ꢁz + 1; (b) x + 0.5, ꢁy + 0.5, ꢁz + 1; (c) ꢁx + 0.5,
yꢁ0.5, z; (d) x + 0.5, y, ꢁz + 0.5.
Bond angles
N(1)AC(2)AC(3)
C(2)AC(3)AC(4)
C(3)AC(4)AC(5)
111.95(9)
110.11(9)
111.88(9)
111.72(10)
109.09(9)
112.47(9)
111.44(9)
111.04(9)
116.60(9)
118.92(10)
124.46(10)
120.11(10)
119.78(11)
120.76(11)
119.63(11)
120.83(11)
118.87(10)
119.60(10)
121.53(10)
116.09(10)
121.05(10)
122.86(10)
122.06(10)
117.83(10)
108.27
109.45
111.96
111.62
109.76
111.79
112.83
109.58
120.97
117.57
121.43
119.30
120.17
120.97
119.28
120.97
119.32
119.08
121.60
115.06
122.33
122.61
122.43
118.27
111.05
111.31
110.95
111.36
109.96
113.82
111.19
112.84
116.36
116.50
127.13
119.27
120.21
120.97
119.21
121.08
119.24
118.97
121.79
115.38
122.17
122.42
122.42
112.31
the Pbca space group and it is isostructural with P3CꢀHBA [5]. As in
the P3CꢀHBA structure, no proton transfer has occurred between
the two components of the complex. However, the O(3)AHꢀ ꢀ ꢀO(1)
hydrogen bond of 2.537(1) Å is by 0.03 Å longer than in P3CꢀHBA.
The P3C molecule exists in zwitterionic form with the carboxylate
group in the axial orientation, stabilized by an intramolecular
N(1)+AHꢀ ꢀ ꢀO(2) hydrogen bond (Table 4). The piperidinium ring
has a slightly flattened chair conformation, the mean endocyclic
torsion angle being 55.4°. The zwitterion interacts with its two
crystallographic copies via the remaining two N(1)+AH donors, to
form hydrogen bonds with the carboxylate acceptors (Fig. 2). In
this scheme, the axial N(1)+AH hydrogen atom participates in a sys-
temof bifurcatedhydrogenbonds, oneintermolecularand oneintra-
molecular, with N+ꢀ ꢀ ꢀO separations of 2.801(1) and 2.847(1) Å,
respectively (Table 4). The intermolecular N(1)+AH(1A)ꢀ ꢀ ꢀO(2)
hydrogen bonds link two P3C molecules into a centrosymmetric
dimer. The equatorial N(1)+AH(1E) donor is linked to the carbox-
ylic O(1) atom of a screw-axis-related P3C molecule (N+ꢀ ꢀ ꢀO dis-
tances 2.799(1) Å) leading to the formation of a chain running
along the a axis. Combination of the inversion symmetry with
the P3C chains leads to molecular layers (at z = 0, ½, . . .) of hydro-
gen-bonded P3C zwitterions that are perpendicular to the c axis.
C(4)AC(5)AC(6)
N(1)AC(6)AC(5)
C(2)AN(1)AC(6)
C(2)AC(3)AC(7)
C(4)AC(3)AC(7)
O(1)AC(7)AC(3)
O(2)AC(7)AC(3)
O(1)AC(7)AO(2)
C(11)AC(12)AC(13)
C(12)AC(13)AC(14)
C(13)AC(14)AC(15)
C(14)AC(15)AC(16)
C(15)AC(16)AC(11)
C(16)AC(11)AC(12)
C(12)AC(11)AC(10)
C(16)AC(11)AC(10)
O(3)AC(10)AC(11)
O(4)AC(10)AC(11)
O(3)AC(10)AO(4)
O(5)AC(12)AC(11)
O(5)AC(12)AC(13)
Torsion angles
N(1)AC(2)AC(3)AC(4)
C(2)AC(3)AC(4)AC(5)
ꢁ53.04(12)
51.44(13)
ꢁ54.40(13)
56.65(13)
ꢁ58.77(12)
58.23(12)
70.64(12)
ꢁ72.48(12)
158.50(10)
ꢁ22.55(14)
ꢁ78.35(12)
100.60(12)
1.16(17)
ꢁ0.62(18)
ꢁ0.57(18)
1.24(18)
ꢁ0.70(17)
ꢁ0.51(16)
ꢁ179.85(10)
178.64(10)
ꢁ173.16(10)
6.73(16)
ꢁ59.15
52.59
ꢁ52.91
53.67
C(3)AC(4)AC(5)AC(6)
ꢁ49.70
ꢁ55.37
C(4)AC(5)AC(6)AN(1)
C(5)AC(6)AN(1)AC(2)
C(6)AN(1)AC(2)AC(3)
N(1)AC(2)AC(3)AC(7)
C(5)AC(4)AC(3)AC(7)
53.01
55.79
ꢁ62.19
65.61
63.14
ꢁ71.62
151.20
ꢁ31.03
ꢁ86.58
91.19
ꢁ56.40
55.33
73.81
ꢁ72.15
ꢁ151.93
29.05
ꢁ26.05
154.93
0.60
O5c
C(2)AC(3)AC(7)AO(1)
C(2)AC(3)AC(7)AO(2)
C(4)AC(3)AC(7)AO(1)
C(4)AC(3)AC(7)AO(2)
C(11)AC(12)AC(13)AC(14)
C(12)AC(13)AC(14)AC(15)
C(13)AC(14)AC(15)AC(16)
C(14)AC(15)AC(16)AC(11)
C(15)AC(16)AC(11)AC(12)
C(16)AC(11)AC(12)AC(13)
C(13)AC(12)AC(11)AC(10)
C(15)AC(16)AC(11)AC(10)
O(3)AC(10)AC(11)AC(12)
O(4)AC(10)AC(11)AC(12)
O(3)AC(10)AC(11)AC(16)
O(4)AC(10)AC(11)AC(16)
O(5)AC(12)AC(11)AC(10)
O(5)AC(12)AC(13)AC(14)
O(5)AC(12)AC(11)AC(16)
O4
O5
O1
O2
ꢁ0.04
O4c
0.02
0.09
O3
0.02
ꢁ0.30
ꢁ0.17
0.85
ꢁ1.05
179.14
ꢁ179.35
ꢁ175.49
2.75
O3c
N1
ꢁ0.04
0.02
O1b
O2a
0.02
ꢁ179.98
ꢁ179.98
179.82
ꢁ0.18
ꢁ0.18
179.82
0.03
O2b
7.51(15)
4.70
ꢁ172.60(10)
ꢁ177.06
ꢁ0.69
ꢁ179.57
179.13
0.68(16)
Fig. 2. Hydrogen-bonding interactions (dash lines) of the P3CꢀSAL unit in the crystal
packing. Superscript labels designate symmetric molecules according to the
definition in Table 4.
ꢁ179.35(10)
ꢁ179.97(10)
179.96
ꢁ179.98

E. Bartoszak-Adamska et al. / Journal of Molecular Structure 920 (2009) 68–74
71
a
1.5
1.0
0.5
0.0
0.2
b
0.1
0.0
-0.1
-0.2
-0.3
3500 3000 2500 2000
1500
1000
500
Wavenumbers (cm-1)
Fig. 3. FTIR spectra of P3CꢀSAL (a) in Nujol and Fluorolube suspensions (dash line—after deuteration), (b) the second-derivative spectrum.
A similar arrangement of P3C molecules was found in the P3CꢀHBA
structure [5].
Table 5
The crystals of the above structural isomers, P3CꢀSAL and
P3CꢀHBA, have significantly different density (1.409 g cmꢁ3 at
100 K vs. 1.432 g cmꢁ3 at 130 K) and melting point (437 and
489 K). The main difference between the two crystal structures is
that the ortho phenolic group of SAL, O(5)AH, is not involved in
any strong intermolecular interactions, and participates only in
an O(5)AHꢀ ꢀ ꢀO(4) intramolecular hydrogen bond of 2.573(1) Å.
Although the C(15)AH group of the phenyl ring acts as a donor
in an intermolecular CAHꢀ ꢀ ꢀO hydrogen bond (Table 4), it does
not compensate for the missing intermolecular O(5)AHꢀ ꢀ ꢀO(4)
hydrogen bond that is present in the crystal structure of P3CꢀHBA
[5]. The result is a less dense crystal with a lower melting point.
A similar behavior of the ortho phenolic OH group was observed
in the MMBꢀSAL complex [10]. The O(5)ꢀ ꢀ ꢀO(4) distance in the pres-
ent structure is slightly shorter than in the crystal of salicylic acid
(2.472(2) Å) [21–23] but longer than in MMBꢀSAL (2.526(2) Å) [10].
This typical intramolecular hydrogen bond between the ortho phe-
nolic OH group and the carboxylate groups is also present in sev-
eral other complexes with the salicylate moiety [24,25]. The
carboxylic group of SAL has the usual cis configuration.
Experimental (dexp) and predicted (dpred) proton and carbon chemical shifts, and
calculated magnetic isotropic shielding tensors (r) in dimethylsulfoxide for the
complex of piperidine-3-carboxylic acid with salicylic acid.
Atoma
dexp
dpred
r
b
1Hc
H(2A)
H(2E)
H(3E)
H(4A)
H(4E)
H(5A)
H(5E)
H(6A)
H(6E)
H(13)
H(14)
H(15)
H(16)
2.95
2.73
28.8737
3.35
2.69
1.57
1.98
1.77
1.66
2.84
3.18
6.66
7.18
6.64
7.69
3.11
2.53
1.73
2.08
2.03
1.46
2.69
2.89
6.77
7.43
6.80
7.80
28.4711
29.0868
29.9193
29.5563
29.6041
30.1982
28.9184
28.7038
24.6481
23.9503
24.6118
23.5695
13Cd
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
43.97
38.17
25.03
21.29
42.90
173.46
172.36
117.74
161.89
116.27
133.04
117.43
130.22
46.39
39.17
25.93
19.92
43.88
180.91
171.87
110.65
161.29
113.17
132.92
114.49
128.16
143.4110
150.2878
162.9140
168.6404
145.8057
15.1877
23.8079
82.1556
33.8859
79.7586
60.9284
78.4997
65.4725
In the crystal packing, there are also some weak CAHꢀ ꢀ ꢀO inter-
actions involving the C(2) piperidinium atom as a donor and the
O(4) salicylic carboxylate atom as an acceptor (Fig. 2, Table 4).
3.2. Vibrational spectra
The solid state FTIR spectrum of P3CꢀSAL is shown in Fig. 3. The
broad absorption, with several submaxima, in the 3100–2450 cmꢁ1
region, is attributed to the OH and NH stretching vibrations of the
groups engaged in the OAHꢀ ꢀ ꢀO (intramolecular) and NAHꢀ ꢀ ꢀO (in-
tra- and inter-molecular) hydrogen bonds. On deuteration, this
absorption shifts to the 2420–2070 cmꢁ1 region. The broad absorp-
tion in the 1510–630 cmꢁ1 region is attributed to the short inter-
molecular OAHꢀ ꢀ ꢀO hydrogen bond. The center of gravity of this
a
For numbering of atoms see Fig. 1; A, axial; E, equatorial.
b
Coefficients for the equation dpred = a + br have been determined by linear
regression as follows: aH = 30.3248; bH = ꢁ0.9954; r = 0.9850; aC = 196.8456;
bC = ꢁ1.0491; r = 0.9983.
c
At 600 MHz.
At 300 MHz.
d

72
E. Bartoszak-Adamska et al. / Journal of Molecular Structure 920 (2009) 68–74
band is at 1160 cmꢁ1. The NH2 scissoring vibration is observed at
ca. 1690 cmꢁ1 and overlaps the
C@O band. After deuteration,
the ND2 scissoring vibration shifts to 1470 cmꢁ1 and the
C@O
and
asCOO bands at 1639 and 1608 cmꢁ1, respectively, are sepa-
rated. In the spectra of P3CꢀHBA [5] and glycine [26], the NH2 scis-
soring vibration was observed at 1670 and 1610 cmꢁ1
respectively. The
asCOO band appears at 1608 cmꢁ1, similarly as
spectrum (d2), the minima have the same wavenumbers as the
maxima in the absorbance spectrum (Fig. 3b). The relative intensi-
ties of the bands in the d2 spectrum vary inversely with the fourth
power of the half-width of the absorption bands [27,28].
m
m
m
,
3.3. NMR spectra
m
in the spectrum of P3CꢀHBA. Using derivative spectroscopy, one
can determine the frequencies of the narrow bands that are cov-
ered by broad absorption, e.g., of dNAH. In the second-derivative
The proton and carbon-13 chemical shifts are listed in Table 5.
The assignments are based on two-dimensional, 1H-1H (COSY) and
1H-13C (HETCOR), experiments. The 1H NMR spectrum is shown in
13,15
2A
16
14
2E
3
6E
6A
5A
4A
5E
7.60 7.40 7.20 7.00 6.80 6.60
4E
NH
4.8 4.6 4.4 4.2 4.0 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4
ppm
Fig. 4. 1H NMR spectrum of P3CꢀSAL in DMSO-d6.
175
150
125
100
75
8
7
6
5
4
3
2
1
50
25
a
b
0
23 24 25 26 27 28 29 30 31
02 55 07 51 00 125 150 175
Magnetic isotropic shielding tensors (cm-1)
Fig. 5. Plots of the proton (a) and carbon-13 (b) chemical shifts vs. magnetic isotropic shielding tensors calculated by the GIAO/B3LYP/6-31G(d,p) method.
Fig. 6. The structures of the P3CꢀSAL monomer and (P3CꢀSAL)2 dimer optimized by the B3LYP/6-31G(d,p) level of theory.

E. Bartoszak-Adamska et al. / Journal of Molecular Structure 920 (2009) 68–74
73
Fig. 4. In analogy to the spectra of piperidine-3-carboxylic acid and
its derivatives [3,29,30] and P3CꢀHBA [5], the spectrum of P3CꢀSAL
is complex. The conformation of P3C itself has been studied by 1H
NMR and the preference for equatorial carboxylate in water solu-
tion has been postulated from vicinal proton–proton coupling con-
stants, which are 9.15 and 3.84 Hz for 3J2a-3 and 3J2e-3, respectively
[29,30]. In the spectrum of the present complex, the coupling con-
zwitterionic piperidinium moieties form a centrosymmetric cyclic
dimer through
pair of N(1)AHꢀ ꢀ ꢀO(2) hydrogen bonds of
a
2.801(1) Å. The dimers are further linked by N(1)AHꢀ ꢀ ꢀO(1) hydro-
gen bonds of 2.799(1) Å. The carboxylate group at C(3) of P3C occu-
pies the axial position and forms an intramolecular hydrogen bond
with the axial N(1)AH donor (N(1)AHꢀ ꢀ ꢀO(2) of 2.847(1) Å). The
phenolic OH and carboxylic groups of the salicylic acid molecule
form the typical intramolecular O(5)AHꢀ ꢀ ꢀO(4) hydrogen bond
(2.573(1) Å). The FTIR spectrum is consistent with the X-ray data
and shows absorption bands in the 3100–2450 and 1500–
600 cmꢁ1 regions that are attributed to the intramolecular and
intermolecular OAHꢀ ꢀ ꢀO and NAHꢀ ꢀ ꢀO vibrations. The linear rela-
tionships between the experimental chemical shifts and the calcu-
lated magnetic isotropic shielding tensors as well as the vicinal
coupling constants confirm the axial arrangement of the carboxyl-
ate group of P3C in solution.
2
3
3
stants are as follows: J2a-2e = 12.60, J2a-3 = 10.8, J2e-3 = 3.60 Hz.
The difference between the observed coupling constants in P3C
in D2O [29,30] and P3CꢀSAL in DMSO-d6 may suggests a predomi-
nance of the axial orientation of the COO group in the title com-
plex. In the spectrum of P3CꢀSAL, the signal of the C(3)AH proton
appears as a triplet of triplets with a band-width of 29 Hz, which
can also suggest predominance of the axial orientation of the
COO group in DMSO-d6 solution [31,32]. The signal of NAH protons
appears at ca. 3.7 ppm. The aromatic ring protons of the SAL moiety
appear in the 6.6–7.7 ppm range.
The relationbetween the experimental 1H and 13C chemical shifts
(dexp) and the gauge including atom orbitals (GIAO) magnetic isotro-
Acknowledgement
pic shielding tensors (
assignments of the proton and carbon-13 chemical shifts. These
relations are described by the following equation: dexp = a + b
r) are usually linear and confirm the correct
´
The DFT calculations were performed at the Poznan Supercom-
puting and Networking Centre.
r
[33,34]. The a and b coefficients are used to calculate the predicted
1H and 13C chemical shifts (dpred) for a given conformer and given
solvent. The data in Table 5 and Fig. 5 show that the agreement
between the experimental and predicted values of the chemical
shifts is very good.
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mer (P3CꢀSAL)2 have been optimized by the B3LYP/6-31G(d,p) ap-
proach (Fig. 6). The data of Table 3 show that the majority of the
bond lengths calculated for (P3CꢀSAL)2 reproduce the experimental
values better than the data calculated for P3CꢀSAL. The calculated
energies for P3CꢀSAL and (P3CꢀSAL)2 are 936.584913 and
1873.200090 a.u., and the theoretical dipole moments are 6.61
and 0.67 D, respectively. The isolated structure of the dimer is by
19 kcal/mol more stable than of the monomer.
In the monomeric P3CꢀSAL molecule, the NAH and COOH cen-
ters of the P3C molecule are neutral, forming an COO(2)AHꢀ ꢀ ꢀN
hydrogen bond of 2.654 Å. The COOH group of P3C is an acceptor
in an intermolecular hydrogen bond of 2.671 Å, donated by the car-
boxylic group of the SAL molecule. The intramolecular hydrogen
bond of the SAL molecule is characterized by an O(5)AHꢀ ꢀ ꢀO(4) dis-
tance of 2.582 Å (Table 4). The carboxylic group of the P3C moiety
is in trans configuration, the O(1)AC(7)AO(2)AH torsion angle
being 176.4°, while in the SAL moiety the configuration of COOH
group has the usual cis configuration, the O(4)AC(10)AO(3)AH tor-
sion angle being 0.14°.
In the optimized structure of (P3CꢀSAL)2, the P3C unit appears in
its zwitterionic form, with equal C(7)AO(1) and C(7)AO(2) bond
lengths (Table 3). The P3C molecules of the (P3CꢀSAL)2 dimer are
linked by two N(1)AHꢀ ꢀ ꢀO(2) hydrogen bonds of 2.604 Å, which in-
volve the axial NAH hydrogen atoms. The equatorial NAH hydro-
gen atom is engaged in an NAHꢀ ꢀ ꢀO(3) hydrogen bond with the
carboxylic group of the SAL moiety. The P3C and SAL units are
linked by an O(3)AHꢀ ꢀ ꢀO(1) hydrogen bond of 2.487 Å, which is
shorter than in the crystal (Table 4).
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4. Conclusions
Piperidine-3-carboxylic acid and salicylic acid form a hydrogen-
bonded 1:1 complex, in which the molecules are linked via the
O(1)ꢀ ꢀ ꢀHAO(3) hydrogen bond of 2.537(1) Å. In the crystal, the

74
E. Bartoszak-Adamska et al. / Journal of Molecular Structure 920 (2009) 68–74
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