Structural conformation of a novel piperidine-4-one derivative: 1-acryloyl-3-methyl-2,6-dip-tolylpiperidine-4-one

Article abstract of DOI:10.1007/s10870-010-9722-x

The novel 3-methyl-2,6-dip-toylpiperidine- 4-one was acylated by 3-chloropropanoychloride and subjected for dehydrohalogenation. The synthesized compound was characterized by spectroscopic techniques and finally confirmed by X-ray diffraction studies. The molecule crystallizes in the monoclinic crystal class in the space group C₂/c with cell parameters a = 18.538(2) A , b = 9.9050(1)A , c = 22.954(2) A , β = 94.486(8)° and Z = 8. The piperidine ring adopts a twist boat conformation. Springer Science+Business Media, LLC 2010.

Full text of DOI:10.1007/s10870-010-9722-x

J Chem Crystallogr (2010) 40:686–690
DOI 10.1007/s10870-010-9722-x
ORIGINAL PAPER
Structural Conformation of a Novel Piperidine-4-One Derivative:
1-Acryloyl-3-Methyl-2,6-Dip-Tolylpiperidine-4-One
•
B. N. Lakshminarayana C. R. Gnanendra
•
•
T. N. Mahadeva Prasad M. A. Sridhar Nagaraja Naik
•
•
•
D. Chenne Gowda J. Shashidhara Prasad
Received: 14 September 2009 / Accepted: 3 February 2010 / Published online: 20 February 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The novel 3-methyl-2,6-dip-toylpiperidine-
4-one was acylated by 3-chloropropanoychloride and sub-
jected for dehydrohalogenation. The synthesized compound
was characterized by spectroscopic techniques and finally
confirmed by X-ray diffraction studies. The molecule crys-
tallizes in the monoclinic crystal class in the space group
and pharmacological properties, which has been reviewed by
Prostakov and Gaivoronskaya [1]. Piperidones are also
reported to possess analgesic, [2, 3] anti-inflammatory, [3]
stimulant and depressant activity on central nervous system
(CNS), [4–8] local anaesthetic, [4, 9] anticancer [10] and
antimicrobial activity [11]. The earlier reports indicated
that the significant biological activities of piperidones
were associated with aromatic substituents at C2 and/or
C6 positions [6, 11]. 5-Alkyl/aryl substituted-1,2,3-tri-
methylpiperidine-4-one were reported to influence arterial
pressure, respiration and nerve activity [12]. A series of
N-methyl-(E)-3,5-bis(arylidine)-4-piperidones carrying a
variety of aryl and heteroaryl groups were reported to have a
combination of antiviral and antitumor activities [13].
N aceylation of substituted piperidine-4-one with chloro-
propanoyl chloride produced biologically active moieties.
˚
C2/c with cell parameters a = 18.538(2) A, b = 9.9050(1) A,
˚
˚
c = 22.954(2) A, b = 94.486(8)° and Z = 8. The piperi-
dine ring adopts a twist boat conformation.
Keywords Alkaloid Á Piperidine-4-one Á
Chloropropanoylchloride Á Twist boat conformation
Introduction
The nitrogen heterocyclics particularly piperidines are an
important group of compounds in the field of medicinal
chemistry owing to the fact that these can frequently be rec-
ognized in the structure of numerous naturally occurring
alkaloid and synthetic compounds with interesting biological
Experimental Section
Melting point of the molecule was determined using
Thomas Hoover apparatus at the heating rate of 1 °C
per minute and was uncorrected. Carbon, nitrogen and
hydrogen contents of the molecule were determined by
micro analytical techniques on Elementar Vario EL III
CHNS (carbon, hydrogen, nitrogen, sulphur) analyzer.
Infrared spectra was recorded on Jasco FT-IR 4100 spec-
trophotometer with potassium bromide pellets in the region
3,500–500 cm-1 and only significant absorption levels are
listed. The H1 NMR spectra of the molecules were recor-
ded using TMS (tetramethylsilane) as a reference standard
in DMSO-d6 (dimethyl sulfoxide duterated) solvent on
Bruker AMX 300 MHz High Resolution Multinuclear FT-
NMR Spectrometer and mass spectra on a Waters-Q-TOF
Ultima spectrophotometer.
B. N. Lakshminarayana Á T. N. M. Prasad Á
M. A. Sridhar Á J. S. Prasad (&)
Department of Studies in Physics, University of Mysore,
Manasagangotri, Mysore 570 006, India
e-mail: jsp@physics.uni-mysore.ac.in;
prasad_1947@yahoo.com
C. R. Gnanendra Á N. Naik Á D. C. Gowda
Department of Studies in Chemistry, University of Mysore,
Mysore 570 006, India
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687
Spectral Data of 1-Acryloyl-3-Methyl-2,6-Dip-
Tolylpiperidine-4-One
Synthesis and Crystallization
3-Methyl-2,6-dip-tolypiperidine-4-one was synthesized
according to literature method [14] by the condensation of
2-butanone, p-tolaldehyde and ammonium acetate in 1:2:1
ratio. Further it was acylated as follows. To a well stirred
solution of 3-methyl-2,6-dip-tolylpiperidin-4-one (5 mmol)
in benzene (30 mL) and triethylamine (15 mmol), 3-chlo-
ropropanoyl chloride in benzene (20 mL) was added slowly
for about an hour. Then the reaction mixture was stirred at
room temperature for about 4–5 h. After completion of the
reaction, it was poured into cold water (500 mL) and
extracted in ethyl acetate twice in 50 mL portions. The ethyl
acetate layer was washed with 5% sodium bicarbonate
solution followed by distilled water. Further, it was dried in
Analytical data; experimental (calculated) C = 79.69
(79.51), H = 7.46(7.25), N = 4.14(4.03); Melting point:
124 °C; Yield:92.3%; MS(m/z):347; IR (KBr, cm-1):3096,
3028, 2974, 2940, 2877, 2824 (C–H stretching), 1720(C=)
stretching), 1645 (N–C=O stretching), 1609, 1513, 1451,
1371, 1327, 1266, 1183, 1119, 1050, 977, 825, 798, 548.
1H NMR (d, ppm): 3.1 (d, CH, 1H, C5a); 2.85 (dd, CH, 1H,
C5b); 3.05 (t, CH, 1H, C3); 6.3 and 5.6 (d, CH2, 2H,
CH=CH2); 6.5 (t, CH, H, CH–C=o); 5.26 (s, CH, 1H, C2);
5.75 (s,CH, 1H, C6); 7.13–7.33 (m Ar–H, 8H, aromatic
protons); 1.06 (d, CH3, 3H, CH3, at C3); 2.35 (s, CH3, 6H,
2CH3 in two benzene ring).
O
H3C
O
N
O
H3C
Cl
Cl
N
H
rt4−5 hours
Benzene
triethylamine
CH3
H3C
O
CH3
H3C
Cl
C2H5OH
Boil
O
H3C
N
H3C
CH3
O
CH2
1−acryloyl−3−methyl−2,6−dip−tolylpiperidin−4one
Scheme 1 Synthesis of 1-acryloyl-3-methyl-2,6-dip-tolylpiperidine-4-one
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image plate was set to a period of 400s. Thirty-six frames
of data were collected in the oscillation mode with an
oscillation range of 5° and processed using Denzo [15].
The reflection were merged with Scalepack. All the frames
could be indexed using a primitive monoclinic lattice. The
structure was solved by direct methods using SHELXS-97
[16]. Least-squares refinement using SHELXL-97 [16]
with isotropic displacement parameters for all the non-
hydrogen atoms converged the residual to R1 = 0.1790.
Subsequent refinements were carried out with anisotropic
Table 1 Experimental crystallographic data
Empirical formula
Formula weight
Temperature
C24H27NO3
377.47
293(2)K
˚
Wavelength
0.71073 A
Monoclinic
C2/c
Crystal system
Space group
˚
a = 18.538(2) A
Cell dimensions
˚
b = 9.9050(1) A
˚
c = 22.954(2) A
b = 94.486(8)°
4201.9(8) A
3
˚
˚
Table 2 Bond lengths (A) and bond angles (°)
Volume
Z
8
Atoms
Length
Atoms
Length
Density (calculated)
Absorption coefficient
F000
1.193 Mg/m3
0.078 mm-1
O10–C9
1.223(3)
1.363(3)
1.486(3)
1.486(3)
1.206(3)
1.376(4)
1.387(4)
1.518(4)
1.486(4)
1.500(5)
1.527(4)
1.552(4)
1.507(5)
1.387(4)
1.391(4)
123.6(2)
116.3(2)
119.4(2)
117.7(3)
120.9(3)
121.3(3)
120.8(3)
120.3(3)
118.8(3)
112.1(3)
112.4(2)
111.4(3)
112.3(2)
110.5(2)
109.9(2)
122.9(3)
121.4(3)
115.7(2)
117.0(3)
123.5(3)
119.4(3)
C20–C2
1.520(4)
1.384(5)
1.392(5)
1.526(4)
1.371(5)
1.308(4)
1.387(5)
1.384(6)
1.381(5)
1.514(5)
1.365(5)
1.369(5)
1.518(6)
1.318(7)
1.499(1)
121.0(3)
120.6(4)
112.5(2)
108.4(2)
116.3(2)
121.5(3)
112.4(3)
121.3(3)
121.5(3)
121.1(3)
121.9(3)
117.0(3)
122.1(3)
120.9(3)
121.1(3)
122.1(4)
117.3(3)
121.5(4)
121.2(4)
115.2(7)
N1–C9
C25–C24
1616
N1–C6
C18–C17
Crystal size
0.30 9 0.27 9 0.25 mm
2.88°to 25.03°
-21 B h B 22
-11 B k B 11
-25 B l B 25
6442
N1–C2
C2–C3
Theta range for data collection
Index ranges
O7–C4
C21–C22
C13–C18
C11–C12
C13–C14
C24–C23
C13–C6
C17–C16
Reflections collected
C9–C11
C22–C23
Independent reflections
Absorption correction
Refinement method
3536 [R(int) = 0.0343]
None
Full-matrix least-squares on F2
C5–C4
C23–C26
C5–C8
C14–C15
C5–C6
C15–C16
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2r(I)]
R indices (all data)
3536/0/257
C4–C3
C16–C19
1.042
C20–C21
O30–C31
R1 = 0.0727, wR2 = 0.2107
R1 = 0.0995, wR2 = 0.2429
C20–C25
O30–O30
-3
C9–N1–C6
C9–N1–C2
C6–N1–C2
C18–C13–C14
C18–C13–C6
C14–C13–C6
O10–C9–N1
O10–C9–C11
N1–C9–C11
C4–C5–C8
C4–C5–C6
C8–C5–C6
N1–C6–C13
N1–C6–C5
C13–C6–C5
O7–C4–C5
O7–C4–C3
C5–C4–C3
C21–C20–C25
C21–C20–C2
C25–C20–C2
C24–C25–C20
C13–C18–C17
N1–C2–C20
N1–C2–C3
C20–C2–C3
C22–C21–C20
C4–C3–C2
C12–C11–C9
C25–C24–C23
C16–C17–C18
C21–C22–C23
C22–C23–C24
C22–C23–C26
C24–C23–C26
C15–C14–C13
C14–C15–C16
C15–C16–C17
C15–C16–C19
C17–C16–C19
C31–O30–O30
˚
0.293 and -0.387 e. A
Largest diff. peak and hole
CCDC deposit number
CCDC 747592
anhydrous sodium sulphate and distilled under reduced
pressure to get crude 1-(3-chloropropanoyl)-3-methyl-2,6-
dip-tolylpiperidine-4-one. This semisolid was dissolved in
excess of distilled ethanol and heated to boil. The title
compound was crystallized by slow evaporation in ethanol.
The crystals were filtered washed with distilled ethanol
and desiccated (Scheme 1). The constitution of 1-acryloyl-
3-methyl-2,6-dip-tolylpiperidine-4-one was supported by
IR, 1H & 13C NMR and Mass spectral studies.
Crystal Structure Determination
A single crystal of suitable size was chosen for X-ray
diffraction studies. The data were collected at room tem-
perature on a DIPLabo Image Plate system with graphite
monochromated radiation MoKa. Each exposure of the
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J Chem Crystallogr (2010) 40:686–690
689
Results and Discussion
The details of crystal data and refinement are given in
Table 1. The bond lengths and bond angles of all the non-
hydrogen atoms (Table 2) are in good agreement with the
standard values[17]. Figure 1 represents the ORTEP [18]
diagram of the molecule with thermal ellipsoids drawn at
50% probability. In the title compound C24H27NO3, the
heterocyclic ring adopts a twist boat conformation with
˚
the atoms N1 and C6 deviating by 0.396(3) A and
˚
-0.275(3) A from the plane (Cremer and Pople, 1975)
defined by the atoms N1/C2/C3/C4/C5/C6. The ring-
˚
puckering parameters [19] are given by Q = 0.692(3) A,
h = 92.5(2)° and / = 256.0(3)°, respectively. The sub-
stituent at C6 is in equatorial conformation as indicated by
the dihedral angle of 85.62(2)° between piperidine and
phenyl ring and the substituent at C2 has a dihedral angle
of 68.36(2)° between the piperidine ring and phenyl ring.
The piperidine ring in the molecule has a weighted average
torsion angle of 37.47°. The torsion angle value of
-177.7(3)° for N1–C2–C3–C8 indicates that methyl group
substituted at C3 is oriented in -anti-periplanar
conformation. The torsion angle value of 176.5(3)° for
C2–N1–C9–O10 indicates that O10 is oriented in ?anti-
periplanar conformation. The acryloyl group substi-
tuted at N1 is oriented in ?anti-periplanar confor-
mation as indicated by the torsion angle value of 165.9(2)°
for C6–N1–C9–C11. No classic hydrogen bonds are
observed. The packing of the molecules down a axis is
shown in the Fig. 2.
Fig. 1 ORTEP of the molecule with thermal ellipsoids drawn at 50%
probability
thermal parameters for the non-hydrogen atoms. After
eight cycles of refinement the residuals converged to
0.0727. The hydrogen atoms were fixed at chemically
acceptable positions and were allowed to ride on their
parent atoms. The crystallographic data have been depos-
ited in Cambridge Crystallographic Data Center, under
reference CCDC 747592.
Fig. 2 Packing of the molecule
when viewed along the a axis
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J Chem Crystallogr (2010) 40:686–690
Acknowledgments The authors are grateful to DST and Govern-
ment of India project SP/I2/FOO/93 and University of Mysore,
Mysore for financial assistance.
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ND, Lin S, Stashenko EE, Prostakov NS, Andreeva EI (1989)
Khim Farm Zh 23:421–427
12. Iskarev NA, Shadurskii KS Tokisal (1965) 28(2):184, Chem
Abstr X63:8920e
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