X-ray diffraction and VT-NMR studies of (E)-3-(piperidinyl)-1-(2′-hydroxyphenyl)-prop-2-en-1-one

Article abstract of DOI:10.1016/j.molstruc.2014.08.016

A series of 1-aryl-3-(cyclicamino)-prop-2-en-1-one analogs was synthesized from commercial acetophenones in 2 or 3 steps. Compound 6, (E)-3-(piperidinyl)-1-(2′-hydroxyphenyl)-prop-2-en-1-one, exhibited the unique shape and intensity of the C_sp2

Full text of DOI:10.1016/j.molstruc.2014.08.016

Accepted Manuscript
X-ray diffraction and VT-NMR studies of (E)-3-(piperidinyl)-1-(2′-hydroxy-
phenyl)-prop-2-en-1-one
Seunghyun Choi, YunHye Kim, Bernie Byeonghoon Park, Suzie Park,
Jonghyun Park, Kiwon Ok, JaeHyung Koo, Yong Woo Jung, Young Ho Jeon,
Eun Hee Lee, Ken S. Lee, Youngjoo Byun
PII:
S0022-2860(14)00835-7
DOI:
http://dx.doi.org/10.1016/j.molstruc.2014.08.016
MOLSTR 20876
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Revised Date:
Accepted Date:
29 May 2014
5 August 2014
5 August 2014
Please cite this article as: S. Choi, Y. Kim, B.B. Park, S. Park, J. Park, K. Ok, J. Koo, Y.W. Jung, Y.H. Jeon, E.H.
Lee, K.S. Lee, Y. Byun, X-ray diffraction and VT-NMR studies of (E)-3-(piperidinyl)-1-(2′-hydroxyphenyl)-
prop-2-en-1-one, Journal of Molecular Structure (2014), doi: http://dx.doi.org/10.1016/j.molstruc.2014.08.016
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Aug 5, 2014
Re: Cover letter for L05-77-14
Dear Dr. Jaan Laane
Attached are further corrections and improvements to our manuscript, X-ray diffraction and
VT-NMR studies of (E)-3-(piperidinyl)-1-(2′-hydroxyphenyl)-prop-2-en-1-one, performed in
response to the comments of Reviewers. The rigor of the reviewers has challenged us to
improve the quality of the manuscript greatly. We have answered all queries and comments.
If further information is required, please do not hesitate to contact me. Thank you for the very
careful review and the opportunity to provide these corrections and re-submit to Journal of
Molecular Structure.
Yours sincerely,
Youngjoo Byun, Ph. D.
College of Pharmacy, Korea University
2511 Sejong-ro, Jochiwon-eup, Sejong 339-700, South Korea
Tel: 82-41-860-1619, Fax: 82-41-860-1606, E-mail: yjbyun1@korea.ac.kr
1

X-ray diffraction and VT-NMR studies of
(E)-3-(piperidinyl)-1-(2′-hydroxyphenyl)-prop-2-en-1-one
a,#
a,#
a
a
a
Seunghyun Choi, YunHye Kim, Bernie Byeonghoon Park, Suzie Park, Jonghyun Park,
a
b
a
a
a
c
Kiwon Ok, JaeHyung Koo, Yong Woo Jung, Young Ho Jeon, Eun Hee Lee, Ken S. Lee,
a,d,
Youngjoo Byun
*
a
College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 339-700,
South Korea.
b
Department of Brain Science, Daegu Gyeongbuk Institute of Science & Technology, 50-1
Sang-Ri, Hyeonpung-Myeon, Dalseong-Gun, Daegu, 711-873, South Korea
c
Department of Chemistry & Biochemistry, Jackson State University, 1400 J. R. Lynch Street,
Jackson, MS 39217, USA
d
Biomedical Research Center, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu,
Seoul 152-703, South Korea
#
Equal contribution
*Corresponding author:
Youngjoo Byun, Ph.D.
College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 339-700,
South Korea.
Tel.: 82-44-860-1619; Fax: 82-44-860-1607; E-mail: yjbyun1@korea.ac.kr
2

Abstract
A series of 1-aryl-3-(cyclicamino)-prop-2-en-1-one analogs was synthesized from
commercial acetophenones in 2 or 3 steps. Compound 6, (E)-3-(piperidinyl)-1-(2′-
hydroxyphenyl)-prop-2-en-1-one, exhibited the unique shape and intensity of the Csp2-N-CH
2
1
13
peaks in the H- and C-NMR spectra. Variable temperature (VT) nuclear magnetic
resonance (NMR) and X-ray diffraction (XRD) studies of 6 revealed that the piperidine ring
has a lower energy barrier to rotation than the 5-membered pyrrolidine 9 due to the less
effective πelectron delocalization along the Csp2-N bond.
Key Words: Enaminones, X-ray diffraction, VT-NMR, Flexible rotation
Research Highlights
ꢀ
ꢀ
ꢀ
ꢀ
(E)-Selective synthesis of 3-(piperidinyl)-1-(2′-hydroxyphenyl)-prop-2-en-1-one.
3D structure determination of the compound by X-ray diffraction.
Spectroscopic characterization of the compounds by 1D and 2D NMR.
Flexible rotation of the compound along the C-N bond explained by VT-NMR studies.
3

1
. Introduction
Enaminones, consisting of the conjugated N-C=C-C=O system, are attractive
functional groups in the field of medicinal chemistry because of their versatile utilization as
intermediates for the synthesis of pharmacologically active agents [1-3]. They have been
widely used as important intermediates and building blocks for preparing heterocyclic
moieties, including quinolones, indoles, isoxazoles, and pyridines, because they can act not
only as nucleophiles but also as electrophiles in a variety of chemical reactions [4-9]. Some
of the enaminone-containing molecules were used as key intermediates for the synthesis of
FDA-approved drugs such as ciprofloxacin and imatinib [10, 11]. Despite the importance of
enaminone systems in synthetic chemistry and medicinal chemistry, few reports have been
published on the structural analysis of enaminone systems by X-ray crystal analysis and
variable-temperature (VT)-nuclear magnetic resonance (NMR) experiments [12-16].
In general, substituted enaminones are classified into (E) and (Z) geometrical isomers
based on the relative position of substituents with higher priorities of the carbon-carbon
double bond. They are also classified into s-cis and s-trans conformational isomers based on
the relationship of alkene and carbonyl groups around the central single C-C bond. For
example, 3-(dimethylamino)-1-(2′-hydroxyphenyl)prop-2-en-1-one (Figure 1) has four
possible isomeric forms: (E)-s-trans, (Z)-s-trans, (E)-s-cis, and (Z)-s-cis. In this study, we
synthesized 1-aryl-3-(cyclicamino)-prop-2-en-1-one analogs and fully analyzed the chemical
structure of (E)-3-(piperidinyl)-1-(2′-hydroxyphenyl)prop-2-en-1-one, one of the analogs, by
means of X-ray crystallography and VT NMR spectroscopy.
4

2
. Experimental
General
1
13
Chemicals and solvents were purchased from Aldrich and Acros. H NMR and C NMR
spectra were recorded on a BRUKER Biospin AVANCE 600 MHz and 300 MHz
spectrometer. Chemical shifts are reported as δ values downfield from internal TMS in
appropriate organic solvents. Mass spectra were recorded on Agilent 6530 Accurate mass Q-
TOF LC/MS spectrometer. HPLC were recorded on Agilent HPLC 1260 Infinity. Silica gel
column chromatography experiments were performed using Merck Silica Gel F254. VT NMR
experiments were carried out by cooling and heating the probe. For VT NMR studies the
sample was placed in the probe and allowed to equilibrate to the required temperature for 30
min.
Synthesis of compounds 6 and 9
(E)-3-(Dimethylamino)-1-(2′-hydroxyphenyl)-prop-2-en-1-one (5)
To a solution of 2'-hydroxyacetophenone (2.73 g, 20 mmol) in p-xylene (20 mL) was
added dimethylformamide-dimethylacetal (DMF-DMA) (2.34 g, 20 mmol). The reaction
mixture was stirred under reflux for 2 hr. After monitoring the progress of the reaction by
TLC, the excessive solvent was removed under reduced pressure. The precipitate solid was
collected by filtration and washed with ethanol. Crystallization from ethanol afforded the
compound 5 (hexane/ethyl acetate = 1.5:1, R
f
= 0.22) in 79% yield as orange-red solid.
), 3.19 (s, 3H, NCH ), 5.78 (d, 1H,
1
H NMR (300 MHz, CDCl
3
): δ2.97 (s, 3H, NCH
3
3
J = 12.2 Hz, =CH-), 6.82 (m, 1H, J = 1.2, 8.1 Hz, Ar-H), 6.93 (dd, 1H, J = 1.0, 8.3 Hz, Ar-H),
7.32-7.38 (m, 1H, J = 1.6, 7.3, 8.7 Hz, Ar-H), 7.69 (dd, 1H, J = 1.6, 8.0 Hz, Ar-H), 7.90 (d,
5

1
3
1
H, J = 12.1 Hz, =CH-), 13.93 (s, 1H, OH). C NMR (75 MHz, CDCl
3
): δ37.39 (NCH
3
),
4
5.33 (NCH ), 90.13 (=CH-), 117.95, 118.24, 120.36, 128.21, 133.94, 154.71, 162.98, 191.56
3
+
(
, 2
C=O). HRMS (ESI): [M+H] calcd for C11H14NO (m/z): 192.1025, found: 192.1018.
3
-Acetyl-4H-chromen-4-one (8)
To a solution of compound 5 (1.90 g, 10 mmol) in acetonitrile (30 mL) was added
pyridine (25 mL) and acetic anhydride (4.8 g, 40 mmol). The reaction mixture was refluxed
for 4 hr. After monitoring the progress of the reaction by TLC, the excessive solvent was
removed under reduced pressure. The residue was extracted with ethyl acetate (100 mL) and
washed with 1 N HCl solution (100 mL x 2). The combined organic layer was dried over
MgSO4, filtered and concentrated under reduced pressure. Purification by silica-gel
chromatography (hexane/ethylacetate = 5:1, R = 0.33) afforded the compound 8 in 52% yield
f
as a white solid.
1
H NMR (300 MHz, CDCl
3
3
): δ2.77 (s, 3H, COCH ), 7.28-7.50 (m, 2H, J = 0.9, 7.1
Hz, Ar-H), 7.53 (d, 1H, J = 8.4 Hz), 7.72-7.77 (m, 1H, J = 1.4, 8.5 Hz, Ar-H), 8.31 (d, 1H,
1
3
J = 7.9 Hz, Ar-H), 8.63 (s, 1H, Ar-H). C NMR (75 MHz, CDCl
3
): δ31.54 (COCH
3
), 118.27,
122.86, 125.43, 126.29, 126.47, 134.33, 155.88, 161.67, 175.32, 196.68 (C=O). HRMS (ESI):
+
[
, 9 3
M+H] calcd for C11H O (m/z): 189.0552, found: 189.0504.
(
E)-1-(2′-Hydroxyphenyl)-3-(piperidin-1-yl)-prop-2-en-1-one (6)
To a solution of compound 8 (0.262 g, 1.4 mmol) in chloroform (30 mL) was added
piperidine (14 mmol). The reaction mixture was stirred under reflux for 6 hr. After
monitoring the progress of the reaction by TLC, the excessive solvent was removed under
reduced pressure. The residue was extracted with ethyl acetate (50 mL) and washed with 1 N
6

HCl solution (50 mL x 2). The organic layer was dried over MgSO4, filtered and concentrated
under reduced pressure. Purification by silica gel chromatography (hexane/ethyl acetate=5:1,
R
f
= 0.26) provided compound 6 in 32% yield in white solid.
1
H NMR (300 MHz, CDCl
), 5.88 (d, 1H, J = 12.3 Hz, =CH-), 6.81 (dd, 1H, J = 7.6 Hz, Ar-H), 6.93 (d,
H, J = 8.3 Hz, Ar-H), 7.27-7.37 (m, 1H, J = 1.1, 7.1, 8.3 Hz, Ar-H), 7.67 (d, 1H, J = 1.1, 8.0
3
): δ 1.69 (s, 6H, N(CH
2 2 2 3
) (CH ) ), 3.41 (s, 4H,
2 2 2 3
N(CH ) (CH )
1
1
3
3
Hz, Ar-H), 7.86 (d, 1H, J = 12.3 Hz, =CH-), 14.02 (s, 1H, OH). C NMR (75 MHz, CDCl ):
δ23.97, 30.89, 44.81, 89.09, 117.89, 118.25, 120.51, 128.08, 133.83, 153.44, .162.93, 191.81
+
(C=O). HRMS (ESI): [M+H]
,
calcd for C11H14NO
2
(m/z): 232.1338, found: 232.1346.
(E)-1-(2′-Hydroxyphenyl)-3-(pyrrolidin-1-yl)-prop-2-en-1-one (9)
Compound 9 was prepared according to the procedure described for compound 6 using
pyrrolidine instead of piperidine.
1
Yield: 22% R
m, 2H, NCH CH ), 2.03-2.12 (m, 2H, NCH
6.6 Hz, NCH CH ), 5.74 (d, 1H, J = 12.1 Hz, =CH-), 6.79-6.84 (m, 1H, J = 1.2,7.3, 8.0 Hz, Ar-H),
.93 (d, 1H, J = 1.0, 8.3 Hz, Ar-H), 7.32-7.38 (m, 1H, J = 1.6, 7.3, 8.5 Hz, Ar-H), 7.69 (dd, 1H, J =
f
= 0.37 (hexane/ethyl acetate=3:2), H NMR (300 MHz, CDCl
3
): δ1.93-2.01
(
2
2
2
CH
2
), 3.33 (t, 2H, J = 6.9 Hz, NCH
2
CH
2
), 3.61 (t, 2H, J
=
2
2
6
1
1
3
.5, 8.0 Hz, Ar-H), 8.10 (d, 1H, J = 12.1 Hz, =CH-), 14.03 (s, 1H, OH). C NMR (75 MHz, CDCl
5.17 (NCH CH ), 47.17 (NCH CH ), 52.69 (NCH CH ), 90.92, 117.90, 118.21, 120.38, 128.21,
2
33.84, 150.42, 162.97, 191.23 (C=O). HRMS (ESI): [M+H] calcd for C11H14NO (m/z): 218.1181,
3
): δ
2
1
2
2
2
2
2
2
+
,
found: 218.1180.
X-ray crystallography
X-ray intensity data for compounds 6 and 9 were collected on a Bruker SMART APEX-II
CCD diffractometer using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å) at a
7

temperature of 296 K or 173 K. The structures were solved by applying the direct method
2
using a SHELXS-97 and refined by full-matrix least-squares calculation on F using
SHELXL-97. All non-hydrogen atoms were refined anisotropically. Amine H atoms were
located in a difference map and refined freely [refined distances; N-H = 0.73 (3) and 0.96 (2)
Å]. Other H atoms were positioned geometrically and refined using a riding model, with C-H
=
0.93-0.98 Å with Uiso = 1.2 Ueq (carrier C) for aromatic- and methylene-H, and 1.5
eq(carrier C) for methyl-H atoms. Crystallographic details for compounds 6 and 9 are
U
summarized in Table 1.
3
. Results and Discussion
′-Hydroxyphenylenaminone analogs were prepared by using the synthetic procedure
3
shown in Scheme 1. Briefly, the reaction of N,N-dimethylformamide-dimethylacetal (DMF-
DMA) with 3′-hydroxyacetophenone in p-xylene under reflux afforded (E)-3-
(dimethylamino)-1-(3′-hydroxyphenyl)prop-2-en-1-one (2). Treatment of 2 with pyrrolidine
or piperidine under acidic conditions gave the corresponding (E)-3-(pyrrolidinyl)-1-(3′-
hydroxyphenyl)-prop-2-en-1-one (3) and(E)-3-(piperidinyl)-1-(3′-hydroxyphenyl)-prop-2-en-
1
-one(4) in 65% and 52% yield, respectively. In the case of 2′-hydroxyacetophenone analogs,
however, a mixture of geometrical (E) isomer 6 and (Z) isomer 7 was obtained in 5:4 ratio
Scheme 1). The pure isomer could not be isolated from a (E/Z) mixture by normal silica-gel
(
column chromatography due to the complete overlap of the two isomers. The (E) and (Z)
composition ratio was calculated based on the integration and coupling constant of vicinal
1
hydrogens of the alkene group from H NMR experiment.
In order to prepare the (E)-isomer 6 exclusively, we used the alternative synthetic
8

route shown in Scheme 2. (E)-1-(2′-hydroxyphenyl)-3-(piperidin-1-yl)-prop-2-en-1-one (6)
was synthesized from 2′-hydroxyacetophenone in 3 steps. The key intermediate, 3-
acetylchromone 8, was prepared by reacting 5 with acetic anhydride in pyridine by modifying
the published synthetic procedure [17]. Treatment of 8 with piperidine in chloroform under
reflux induced the ring opening of the pyrone ring to afford the (E)-isomer 6 exclusively
without generating the (Z)-isomer 7 in 32% yield. When compound 8 was reacted with
pyrrolidine and piperazine instead of piperidine under the same conditions, the corresponding
enaminones 9 and 10 were obtained in (E)-isomeric form. The electron-withdrawing acetyl
group of 8 decreases the electron density of the C-2 atom and acts as a 1,4-addition reaction
acceptor. Nucleophilic attack of cyclic amines induces the concomitant opening of the pyrone
ring, followed by deacetylation under reflux.
1
13
1
Compound 6 was fully analyzed by H, C, and 2D NMR experiments. H NMR
shows each proton’s peak, as expected, with a proper integration. The proton of the hydroxyl
group appeared at 14.1 ppm. Two olefin hydrogen atoms at 7.86 ppm and 5.88 ppm were
confirmed by correlation spectroscopy (COSY) experiment and its coupling constant (J =
1
2.3 Hz) proved that the compound has (E) conformation. Six protons of the piperidine ring
gave peaks at 1.69 ppm (6Hs) and 3.41 ppm (4Hs, two of –N-CH -), which were a broad
2
singlet, but the COSY experiment confirmed that were coupled with each other. Five carbons
of the piperidine ring are observed at 23.9 ppm, 25.1 ppm, 26.4 ppm, 46.5 ppm and 55.0 ppm
1
3
in C NMR, but all except that at 23.9 ppm were relatively weak. Heteronuclear correlation
1
13
spectroscopy (HETCOR) experiment between H and C showed that the hydrogen at 3.41
ppm was correlated with the peaks at 46.5 ppm and 55.0 ppm, which were attributed to the
2
methylene group next to nitrogen (-N-CH -) in the piperidine ring, and that the broad peak at
1
.69 ppm was crossed with three carbon peaks at 23.9 ppm, 25.1 ppm, and 26.4 ppm, which
9

were the remaining methylene groups in the piperidine ring. The broadness of the proton
1
13
peaks in H NMR and the small peaks in C NMR revealed that the piperidine ring was
1
13
quickly rotating along the C-N bond. Therefore, we quickly conducted VT H and C NMR
o
o
experiments from 6.2 C to 40 C. The carbon peaks presented a sharper and taller shape as
1
the temperature was decreased. In the H NMR results, the peaks at 3.41 ppm with two
o
o
triplets at 6.2 C were changed into a sharp singlet at 40 C. We observed the coalescence
o
1
2
temperature of N-CH located at 25 C (298K) on H NMR spectrum and the calculated
activation rotational energy was 15.0 kcal/mol (see supporting information for details).
1
VT H NMR indicated that the piperidine ring of compound 6 is rotating fast enough
to show its broadness at room temperature. However, such fast rotation has not been observed
in other enaminone systems substituted with 5-membered pyrrolidine (9) or acyclic N,N-
dimethylamine. The proton peaks of the two methyl groups next to the nitrogen were
separated clearly in the pyrrolidine and N,N-dimethyl analogs (see all spectra in the
supporting information), which revealed that they are not rotating that fast at room
1
13
temperature. However, the H and C NMR spectra of the enaminone of 6-membered
piperazine analog 10 showed broad and weak intensity peaks similar to those of compound 6.
These results indicated that the delocalization of pi-electrons from the nitrogen to carbonyl
may differ different between the 6-membered ring system and the 5-membered or acyclic
systems. The nitrogen in piperidine would not participate in the delocalization as much as the
dimethylamino or pyrrolidine compound would.
To analyze the molecular structure of compound 6 more accurately, its X-ray crystal
structure was determined. The exhibited planar structure shows the hydrogen bonding
between the oxygen of the carbonyl group and the hydrogen of the hydroxyl group on the
phenyl ring, as shown in Figure 3. The distance between the oxygen of the carbonyl group
1
0

and the hydrogen of OH was 1.666Å, which is in the range of normal hydrogen bonding
reported previously with substituted phenyl chalcones [12]. The planarity of compound 6 was
probably due to the delocalized πelectron system from the carbonyl to the nitrogen of the
piperidine ring. The torsional angles around the nitrogen (C8-C7-N1-C6 or C2) of compound
o
o
6
were -0.6 and 168.8 , respectively. The bond lengths and the bond angles around the
nitrogen supported the participation of nitrogen in long conjugation of the π- electron, which
o
was extended to the carbonyl group at least. The bond angles around nitrogen were 120.3 ,
o
o
1
23.0 , and 115.7 and the bond lengths from the nitrogen to the neighboring Csp2 and Csp3
carbons were 1.327 Å and 1.470 Å, respectively. The normal bond lengths for C-N bonds in
the planar structure are in the range of 1.336 Å and 1.473 Å, respectively. The bond lengths
around the carbonyl carbon were 1.491 Å and 1.427 Å for the adjacent carbons, which are
within the range of reported values. However, the bond to the unsaturated carbon was shorter
than the other, since it was involved in the conjugation, as indicated by the bond length of the
carbonyl bond, which at 1.267 Å was slightly longer than that of a non-conjugated carbonyl
group.
Compound 6 exhibited a similar structural feature to the previously reported crystal
structure of (E)-1-(2′-hydroxyphenyl)-3-(N,N-dimethylamino)-prop-2-en-1-one (5). The
striking differences between the two compounds were the intermolecular hydrogen
interactions for packing. The dimethylamino group showed its weak intermolecular hydrogen
interactions between the oxygen of the hydroxyl group and the two C-H units of the α- carbon
and ortho position of the aromatic ring, 2.387 Å and 2.405 Å, respectively. Such interactions
influenced the hydrogen bond by making it stronger. The X-ray results of 6 showed that the
OH bonds with the neighboring carbonyl group were longer (1.032 Å) and shorter (1.500 Å)
than usual. However, the results also showed weak intermolecular interactions between the
1
1

oxygen of the hydroxyl group and the two hydrogen atoms from two piperidine rings of two
different molecules, with distances of 2.545 Å and 2.478 Å. The revealed X-ray crystal
structure indicated that the contribution of the nitrogen in piperidine to the delocalization of
the enaminone was not as much as that of dimethylamine or pyrrolidine compounds. The
enaminone of the dimethylamino group has a shorter distance in hydrogen bonding, 1.50 Å,
compared to 1.666 Å for piperidine. This indicates that the oxygen in the carbonyl is less
negatively charged due to a partial conjugation of π- electron from the nitrogen.
The proton peaks of the two N-CH
centered at 3.60 and 3.33 ppm, respectively (see the supporting information), indicating that
the two N-CH are in different chemical environments. In the X-ray crystal structure of 9 as
2
in the pyrrolidine 9 appeared as two sharp triplet
2
shown in Figure 5, the shorter N(1)-C(6) [1.308 Å] bond distance was observed as compared
to N(1)-C(7) [1.327 Å] for compound 6. This result indicated that the C-N bond of 9 is less
flexible than that of 6 because the delocalization of π electrons in the enaminone system
substituted with the pyrrolidine is more effective than that in the related piperidine 6.
4
. Conclusions
We synthesized a series of (E)-1-aryl-3-(cyclicamino)-prop-2-en-1-one analogs and
1
13
analyzed their structures by means of H and C NMR and liquid chromatography–mass
spectrometry (LC/MS). We developed a synthetic strategy for preparing (E)-1-(2′-
hydroxyphenyl)-3-(piperidin-1-yl)-prop-2-en-1-one (6) and analyzed its structural
characteristics by X-ray crystallography and VT-NMR. The rotational flexibility of the
piperidine ring in compound 6 at room temperature produced the unique shape and intensity
1
13
of the C-N-CH
2
peaks in H-NMR and C-NMR. The X-ray structure of 6 revealed that the
piperidine ring has more flexible rotation along the C-N bond than the 5-membered
1
2

pyrrolidine 9 due to the less effective π- electron delocalization of the enaminone system.
Acknowledgements
This work was supported by the National Research Foundation of Korea (NRF) grant
funded by the Korea Government (No. 2014R1A4A1007304 and No. 2012R1A1A11010000).
Appendix A. Supplementary material
Supplementary data associated with this article and cif files for 6 and 9 can be found
at http://
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(
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15] Y.C. Shi, Y.Y. Hu, J Coord Chem, 62 (2009) 1302-1312.
16] P. Simunek, M. Svobodova, V. Bertolasi, L. Pretto, A. Lycka, V. Machacek, New J Chem, 31
2007) 429-438.
17] I. Yokoe, K. Maruyama, Y. Sugita, T. Harashida, Y. Shirataki, Chem Pharm Bull, 42 (1994) 1697-
1699.
1
4

Legends
Figure 1. Geometrical and conformational isomers of 3-(dimethylamino)-1-(2′-
hydroxyphenyl)prop-2-en-1-one
Figure 2. Variable temperature (VT) NMR spectra: Full screen (a) and expanded spectra
1
around 3.4 ppm (c) in H NMR of temperature control, and full screen (b) and expanded
1
3
spectra around 40 ppm (d) in C NMR of temperature control
Figure 3. Crystal structure of (E)-1-(2′-hydroxyphenyl)-3-(piperidin-1-yl)-prop-2-en-1-one
(6). Selected bond lengths [Å] and angles [deg]; N(1)-C(7) 1.327Å, N(1)-C(6) 1.470Å, N(1)-
C(2) 1.470Å, C(16)-O(17) 1.349Å, C(16)-O(17)-H(17) 102.5°, O(10)-H(17) 1.666Å (est).
Figure 4. The packing diagram of compound 6
Figure 5. Crystal structure of (E)-1-(2′-hydroxyphenyl)-3-(pyrrolidin-1-yl)-prop-2-en-1-one
(9). Selected bond lengths [Å] and angles [deg]; N(1)-C(6) 1.309Å, N(1)-C(5) 1.461Å, N(1)-
C(2) 1.463Å, C(15)-O(16) 1.347Å, C(15)-O(16)-H(16) 107.4 °, O(9)-H(16) 1.572Å (est).
Figure 6. The packing diagram of compound 9
Scheme 1. Synthesis of (E)-3′-hydroxyphenylenaminones
Scheme 2. Synthesis of (E)-2′-hydroxyphenylenaminones
Table 1. Crystal and structure refinement for compounds 6 and 9
1
5

Figure 1.
1
6

Fi
gure 2.
(
a)
(b)
(
c)
(
d)
17

Figure 3.
Figure 4.
1
8

Figure 5.
Figure 6.
1
9

Scheme 1.
Scheme 2.
2
0

Table 1.
Compound
6
9
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
C
14
H
17 NO
2
C
13 2
H15 NO
231.28
173(2)
0.71073
217.26
296 (2)
0.71073
Monoclinic
Orthorhombic
Pna2
1
1
P2 /c
a = 10.9878(2) , α = 90.000
b = 13.5883(4) , β= 90.000
c = 7.9410(10) , γ = 90.000
1185.64(4)
a = 10.3245(16), α = 90.000
b = 9.4867(14) , β= 104.257(2)
c = 11.9731(19) , γ = 90.000
1136.6(3)
Unit cell dimensions (Å), (˚)
3
Volume (Å )
-
3
Z, Calculated density (mg m )
4, 1.296
4, 1.270
-
1
Absorption coefficient (mm )
Crystal size
0.086
0.086
0.23 x 0.22 x 0.22 mm
2.384 to 28.309 deg.
0.23 x 0.22 x 0.20 mm
2.035 to 28.274 deg.
-13 ≤ h ≤ 13,
Theta range for data collection
-
14 ≤ h ≤ 14,
-18 ≤ k ≤ 18,
10 ≤ l ≤ 10
Limiting indices
-12 ≤ k ≤ 12,
-
-15 ≤ l ≤ 15
Reflections collected / unique
Completeness to theta = 25.242
Final R indices [I>2 sigma(I)]
30904 / 2954 [R(int) = 0.0412]
100.0 %
17102 / 2818 [R(int) = 0.0324]
100.0 %
R1 = 0.0323, wR2 = 0.0851
R1 = 0.0688, wR2 = 0.1916
2
1

Graphical abstract
2
2

Highlights
ꢀ
ꢀ
ꢀ
ꢀ
(E)-Selective synthesis of 3-(piperidinyl)-1-(2′-hydroxyphenyl)-prop-2-en-1-one.
3D structure determination of the compound by X-ray diffraction.
Spectroscopic characterization of the compounds by 1D and 2D NMR.
Flexible rotation of the compound along the C-N bond explained by VT-NMR studie
s.
2
3