Synthesis, spectral and single-crystal analyses of new derivatives of 4-amino-N-benzylpiperidine

Article abstract of DOI:10.14233/ajchem.2015.19174

Two new compounds of thiourea derivatives of cinnamoyl and benzoylisothiocyanate with 4-amino-N-benzylpiperidine have been successfully synthesized. The new molecules, 1-(1-benzylpiperidine-4-yl)-3-benzoyl thiourea (I) (yield 83 %) and 1-(1-benzylpiperidi

Full text of DOI:10.14233/ajchem.2015.19174

Asian Journal of Chemistry; Vol. 27, No. 12 (2015), 4457-4460
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.19174
Synthesis, Spectral and Single-Crystal Analyses of New Derivatives of 4-Amino-N-benzylpiperidine
1,*
3
2
IBRAHIM N. HASSAN , MOU’AD A. TARAWNEH and BOHARI M. YAMIN
1School of Environmental and Natural Resource Sciences, Faculty of Science & Technology, National University of Malaysia, 43600 Bangi,
Selangor, Malaysia
2School of Chemical Sciences & Food Technology, Faculty of Science & Technology, National University of Malaysia, 43600 Bangi, Selangor,
Malaysia
3Department of Physics, College of Science, Al-Hussein Bin Talal University, P.O. Box: 20, Ma'an, Jordan
*Corresponding author: Tel: +60 1139438140; E-mail: ibnhum@gmail.com
Received: 13 March 2015;
Accepted: 25 June 2015;
Published online: 29 August 2015;
AJC-17490
Two new compounds of thiourea derivatives of cinnamoyl and benzoylisothiocyanate with 4-amino-N-benzylpiperidine have been
successfully synthesized. The new molecules, 1-(1-benzylpiperidine-4-yl)-3-benzoyl thiourea (I) (yield 83 %) and 1-(1-benzylpiperidine-
4-yl)-3-(3-phenylacryloyl)thiourea (II) (yield 81%) were characterized by NMR, IR, UV, CHNS-O techniques as well as X-ray diffraction
for single crystal. 1H NMR spectra show chemical shift at 10.77-10.80 ppm and 8.98-8.93 ppm were assigned for both δH(N) protons.
Whereas, the chemical shift for 13C NMR analysis for C=O and C=S presence at δC 169-179 ppm. The significant stretching bands for
ν(N-H), ν(C=S), ν(C=O) and ν(C-N) were around 3250, 800, 1650 and 1340 cm-1, respectively. The important chromophore of C=O was
observed with a maximum absorption at around 300 nm in the UV spectra. The structures of (I) and (II) were determined via X-ray
diffraction analysis for single crystal. Both molecules exhibit monoclinic crystal system and adopt trans-cis configuration with respect to
the position of the phenyl and N-benzylpiperidine groups relative to the thione S atom, across their C-N bonds. There is one intramolecular
N-H···O hydrogen bonds in both molecules that lead to the formation of pseudo-six-membered, in addition to a pseudo-five-membered
ring, C9–H9···S1, in (I) which stabilizes the molecule. In the crystal lattice, the molecules are linked by intermolecular hydrogen bonds
C–H···S and C–H···O forming chain network in (I) and polymeric in (II).
Keywords: Thiourea, Benzoyl, 4-Amino-N-benzylpiperidine, X-ray crystallography.
environments15-17. The literature review showed that no work
has been reported on the synthesis of cinnamoyl and benzoyl
thiourea with 4-amino-N-benzylpiperidine. The structural and
spectral properties of 1-(1-benzylpiperidine-4-yl)-3-benzoyl
thiourea (I) and 1-(1-benzylpiperidine-4-yl)-3-(3-phenyl-
acryloyl)thiourea (II) (Fig. 1) are described in this paper.
INTRODUCTION
Thiourea derivatives obtained as aroylthiourea substituted
derivatives are compounds of interest in solid-state chemistry due
to their tendency to the formation of inter- and intramolecular
hydrogen bonds for NH proton donor group to the carbonyl
sulfur and oxygen atoms1-3. In addition to environmental and
industrial applications, thiourea compounds are generally used
in several applications for example anticancer drugs, platelet
antiaggregating, antidepressants, antihyperlipidemic, antibac-
terial, antiparasitic, antiallergic and antiproliferative activity4-6.
Previous studies described that thiourea compounds moieties
have been extensively used as fungicides and insecticides
agent7-10. On the other hand, thiourea compounds are suitable
inclusion compounds or host materials showing various appli-
cations in the development of electronic and optoelectronic
devices11,12. Due to atom sulfur is easily protonated in acidic
solution, thiourea derivatives are effective corrosion inhibitor
agents [13,14]. Thiourea ligand is not sensitive to air and moisture
and heat stable thus the reaction can be carried out in ambient
N
S
O
N
S
O
N
N
N
H
N
H
H
H
(I)
(II)
Fig. 1. Molecular structural representations of (I) and (II)
EXPERIMENTAL
Chemicals used for synthesis the new compounds were
purchased from MERCK or Sigma Aldrich. NMR spectra for
1H 400.11 MHz and 13C 100.61 MHz were recorded using
NMR Bruker Avance III 400 spectrometer in DMSO-d6 as a

4458 Hassan et al.
Asian J. Chem.
1.800
1.500
solvent at room temperature in the range of 0-15 ppm and 0-
200 ppm. Infrared spectra (IR) of the synthesized compounds
were recorded from KBr pellets using Perkin Elmer FTIR 100
spectrophotometer in the range of 4000-400 cm-1. The structures
of the new compounds were solved and refined using SHELX18.
Data collection: SMART19; molecular graphics: SHELXL
9720; cell refinement: SAINT and data reduction: structure:
SHELXS 9721 software used to prepare material for publi-
cation: SHELXTL22 and PLATON software to calculate the
hydrogen bonds23. The view of the molecule was obtained by
using ORTEP-32 for Windows24.
(I)
(II)
1.000
0.500
0
Synthesis of (I) and (II): Benzoyl/cinnamoyl isothiocyanate
was first prepared by adding an acetone solution containing
ammonium thiocyanate into benzoyl/cinnamoyl chloride in
acetone. The mixtures were stirred for 10 min before the preci-
pitate was filtered and washed with cold acetone. The reaction
between of benzoyl/cinnamoyl isothiocyanate and 4-amino-
N-benzylpiperidine in acetone was stirred for 15 min under
70 °C with a mol ratio of 1:1. The mixture was refluxed for
3 h and filtered into a beaker containing some ice. A white
precipitate was formed immediately, filtered and dried. The
isolated product had a melting point of 173.5-175.2°C (Fig. 2).
-0.136
200
300
400
500
Wavelength (nm)
Fig. 3. UV spectra of compounds (I) and (II)
nearby 1666.39 and 1681.87 cm-1 represent the stretching of
ν(C=O) in (I) and (II), respectively and it is decreasing in
frequencies compared with typical carbonyl absorption (1700
cm-1)25. This is due to conjugated resonance of phenyl group
and the formation of intramolecular hydrogen bonding with
N-H26. The stretching vibrations of ν(C-N) band are at 1338.53
cm-1 (I) and 1340.56 cm-1 (II). 907.63 cm-1 (I) and 858.94
cm-1 (II) are assigned for stretching ν(C=S) modes. From IR
spectra analysis (Table-2) show that the thiourea moieties were
formed for compounds (I) and (II) in good agreement with
O
NCS
N
+
NH2
previous studies27,28
.
R
Aroyl
isothiocyanate 4-amino-N-benzylpiperidine
TABLE-2
IR ABSORPTION DATA FOR COMPOUNDS (I) AND (II)
Wavenumber (cm-1)
(I)
R =
=
N
S
O
Compound
ν(N-H)
3243.68
3178.39
ν(C=O)
1666.39
1681.87
ν(C-N)
1338.53
1340.56
ν(C=S)
907.63
858.94
N
N
R
(I)
(II)
(II)
H
H
Fig. 2. Synthetic routes of (I) and (II)
X-ray crystallographic studies: The new molecules were
obtained as single crystals suitable for X-ray analysis (Table-
3). Both (I) and (II) adopt cis-trans configuration with respect
to position of 4-amino-N-benzylpiperidine and phenyl groups
relative to the S atom, across C-N bonds (Figs. 4 and 5). The
central moiety, S1/O1/N1/N2/C6/C7/C8, in compound (I)
[maximum deviation 0.004(3) Å at atom N1] and the phenyl
group (C1-C6) are planar and dihedral angle between the least
planes is 35.51(18)°. The bond length of C=S group of (I)
[1.830(4) Å] is longer than that of (II) [1.673(4) Å]. In com-
pound (II), the dihedral angle between the central fragment,
S1/O1/N1/N2/C7/C8/C9/C10/C11 [maximum deviation
0.006(3) at N1] and phenyl group (C1-C6) is 25.8(15)°. The
fragment C16/C17/C18/C19/C20/C21 in (II) is planar with
maximum deviation of 0.006(5) at C19. The C7-C8, bond
length [1.315(5) Å], has a double bond character with H atoms
at atoms C7 and C8 trans to each other.
RESULTS AND DISCUSSION
Ultraviolet spectra: Ultraviolet absorption for (I) and
(II) show n→π* and π→π* transition (HUMO→LUMO). The
ultraviolet spectra exhibited an important bands for chromophore
carbonyl (C=O) group. Both compounds show maximum
absorption bands for chromophore C=O in compound (I) and
(II) at 325.40 nm and 322.70 nm, respectively (Fig. 3). Table-1
shows the maximum absorption for each compounds; (I) and
(II) from the UV spectra study.
Infrared spectra: The IR spectra revealed the expected
frequencies of the ν(N-H), ν(C=O), ν(C-N) and ν(C=S) in both
compounds. An average intensity bands presence at 3243.68
cm-1 (I) and 3178.39 cm-1 (II) which relates to stretching ν(N-H).
The stretching band of ν(N-H) (I) has higher frequency compa-
ring with compound (II) because of the position the of electron
withdrawing group around NH moiety. The absorption bands
Table-4 presented that the bond lengths and angles were in
normal ranges29 and analogous to other thiourea derivatives30,31
.
TABLE-1
Nevertheless, C8-N1 in (I) is longer than C8-N2. While in
(II), C10-N1 is longer than C10-N2. The differences are probably
because of the interaction of the intramolecular hydrogen
bonding26. C=S and C=O bond distances for both molecules
show the expected double bond character.
UV ABSORPTION OF COMPOUNDS (I) AND (II)
Compound
(I)
ν(C=O) λmax (nm)
325.40
ν(C=O) Transition
n→π*, π→π*
322.70
(II)
n→π*, π→π*

Vol. 27, No. 12 (2015)
Synthesis, Spectral and Single-Crystal Analyses of New Derivatives of 4-Amino-N-benzylpiperidine 4459
TABLE-4
TABLE-3
CRYSTAL DATA FOR COMPOUND (I) AND (II)
SELECTED BOND LENGTHS (Å) AND
ANGLES (°) FOR COMPOUNDS (I) AND (II)
Subject
(I)
(II)
Bond
Angles
distances (°)
Empirical formula
Formula weight
Crystal system
Wavelength
Space group
a (Å)
C20H23N3OS
353.47
Monoclinic
0.71073 Å
P21/c
8.857(7)
20.392(16)
11.953(9)
90
C22H25N3OS
379.51
Monoclinic
Compd.
Bond
Distances
distances (Å)
1.830(4)
1.029(3)
1.625(5)
1.098(3)
1.623(4)
1.319(4)
1.680(5)
1.673(4)
1.219(4)
1.376(4)
1.377(4)
1.314(4)
1.467(4)
S1-C8
C7-N1-C8
C8-N2-C9
C11-N3-C14
N1-C7-C6
N1-C8-N2
S1-C8-N1
O1-C7-N1
C9-N1-C10
C10-N2-C11
O1-C9-N1
S1-C10-N1
N1-C9-C8
N1-C10-N2
144.0(0)
116.0(3)
108.2(3)
135.7(2)
117.1(3)
136.83(18)
115.6(3)
128.3(3)
124.4(3)
122.5(3)
118.4(2)
113.9(3)
117.1(3)
O1-C7
N1-C8
N2-C8
N2-C9
N3-C12
N3-C14
S1-C10
O1-C9
N1-C9
N1-C10
N2-C10
N3-C16
P21/c
(I)
31.033(3)
5.9352(6)
20.0798(14)
90
b (Å)
c (Å)
α (°)
β (°)
100.246(3)
90
1881.2(6)
106.066(13)
90
2075(3)
4, 1.215
0.172
γ (°)
Volume (Å3)
(II)
Z, calculated density (mg/m-3) 4, 1.248
Absorption coefficient (mm-1) 0.184
F(000)
752
808
Crystal size (mm)
Crystal description
Crystal colour
θ Range°
0.36×0.21×0.16
Block
Colourless
1.52-26.0
0.35×0.28×0.21
Block
Colourless
2.00-24.99
H13A···S1, in (II) which further stabilizes the molecule
(Table-5). Compound (I) has shorter hydrogen bond distance
of N2-H2···O1, 3.204(4) Å compare to (II), the distance of
N2-H2···O1 is 2.645(3) Å. This difference indicates an
electronic effect and steric effect of the molecules.
Index ranges
-16 ≤ h ≤ 16
-10 ≤ k ≤ 15
-13 ≤ l ≤ 13
10024/3691
-10 ≤ h ≤ 10
-24 ≤ k ≤ 24
-14 ≤ l ≤ 14
14667/3656
Independent reflections
TABLE-5
[R(int) = 0.0239] [R(int) = 0.0281]
0.9711 and 0.9366 0.9648 and 0.9423
Full-matrix least- Full-matrix least-
INTRAMOLECULAR AND INTERMOLECULAR
HYDROGEN BOND DISTANCES (Å) AND
ANGLES (°) FOR COMPOUNDS (I) AND (II)
Max. and min. transmission
Procession method
squares on F2
3691/0/226
1.222
0.226
-0.168
squares on F2
3656/0/244
1.380
0.193
-0.137
Compound
Intramolecular
(I)
D
A
D-H
H···A
D-H···A
D-H···A
Data/restraints/parameters
Goodness-of-fit on F2
Largest diff. peak (e.A-3)
Largest diff. hole (e.A-3)
R, wR
N2
O1
0.86
0.97
0.86
2.56
2.45
1.96
3.204(4)
2.941(4)
2.645(3)
133
111
136
C13 S1
0.0684, 0.1371
0.0838, 0.1437
0.0840, 0.1524
0.0965, 0.1572
N2
N1
O1
S1
(II)
R,wR (all reflection)
Intermolecular
0.86
0.97
0.86
0.93
0.97
2.27
2.48
2.55
2.72
2.52
3.064(3)
3.125(4)
3.394(4)
3.562(5)
3.382(5)
169
124
165
151
147
(I)
C11 O1
N1
C8
S1
S1
(II)
C16 O1
In the crystal packing of (I), intermolecular hydrogen
bonds N1-H1A···O2 linked the molecules to form polymeric
network. Whereas in (II), the intermolecular hydrogen bonds
N1-H1A···O2 and C2-H2···O1 are forming chain network
(Figs. 6 and 7).
Fig. 4. Molecular structure of (I), (with 50 % probability displacement
ellipsoids) with intramolecular hydrogen bonds
1
Nuclear magnetic resonance: H NMR and 13C NMR
spectra are comparable and reliable with the structures resulted
from the X-ray investigation. The two most de-shielded signals
were represented NH proton at δH 9.12, δH 10.96 ppm (I)
and δH 9.00, δH 10.97 ppm (II). These signals are similar to
those found in the analogous molecules as reported in previous
Fig. 5. Molecular structure of (II), (with 50 % probability displacement
ellipsoids) with intramolecular hydrogen bond
There are two intramolecular hydrogen bonds in (I),
C–H···S and N-H···O, which form two pseudo-six-membered
rings, in addition to a pseudo-six-membered ring, C13–
Fig. 6. Molecular packing of (I) viewed down the c-axis

4460 Hassan et al.
Asian J. Chem.
grants [DPP-2014-098] and the Malaysian Ministry of Science,
Technology and Innovation (MOSTI) for IRPA research grants
[09-02-02-0163].
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The synthesis of two new thiourea derivatives of 4-amino-
N-benzylpiperidine have been carried out and characterized
by using nuclear magnetic resonance analysis (NMR), infrared
(IR) and ultraviolet (UV-visible). The infrared spectra show
the important stretching bands for ν(C=O), ν(N-H), ν(C=S)
and ν(C-N) for (I) and (II). The UV spectra showed that there
is a significant chromophores C=O which is responsible to
n→π* and π→π* transition in both molecules. The structures
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Supplementary data
CCDC1041584 and CCDC1041585 contain the supple-
mentary crystallographic data for (I) and (II), respectively.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
ACKNOWLEDGEMENTS
The authors thank Universiti Kebangsaan Malaysia for
supporting the study and providing the facilities and research