Synthesis, characterization and dynamic NMR studies of a novel chalcone based N-substituted morpholine derivative

Article abstract of DOI:10.1016/j.molstruc.2013.02.029

The synthesis of a novel chalcone based N-substituted morpholine derivative namely, (E)-1-(biphenyl-4-yl)-3-(4-(5-morpholinopentyloxy) phenyl) prop-2-en-1-one (BMPP), using a two step protocol is reported. The compound is characterized by FTIR, GC-MS and FTNMR spectroscopy techniques. Advanced 2D NMR techniques such as gradient enhanced COSY, HSQC, HMBC and NOESY were employed to establish through-bond and through-space correlations. Dynamic NMR measurements were carried out to obtain the energy barrier to ring inversion of the morpholine moiety.

Full text of DOI:10.1016/j.molstruc.2013.02.029

Journal of Molecular Structure 1040 (2013) 90–97
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, characterization and dynamic NMR studies of a novel chalcone
based N-substituted morpholine derivative
R. Baskar a, C. Baby b, M.S. Moni b, K. Subramanian a,
⇑
a Department of Chemistry, Anna University, Chennai, India
b Sophisticated Analytical Instrument Facility, Indian Institute of Technology Madras, Chennai, India
h i g h l i g h t s
"
"
"
"
A novel chalcone based N-substituted morpholine derivative is synthesized.
Complete assignments of 1H and 13C signals were made using modern 2D NMR techniques.
The stereo dynamics of the morphline moiety have been examined by dynamic NMR spectroscopy.
The energy barrier to morphline ring inversion is calculated.
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of a novel chalcone based N-substituted morpholine derivative namely, (E)-1-(biphenyl-4-
Received 23 December 2012
Received in revised form 22 February 2013
Accepted 23 February 2013
Available online 5 March 2013
yl)-3-(4-(5-morpholinopentyloxy) phenyl) prop-2-en-1-one (BMPP), using
a two step protocol is
reported. The compound is characterized by FTIR, GC–MS and FTNMR spectroscopy techniques. Advanced
2D NMR techniques such as gradient enhanced COSY, HSQC, HMBC and NOESY were employed to estab-
lish through-bond and through-space correlations. Dynamic NMR measurements were carried out to
obtain the energy barrier to ring inversion of the morpholine moiety.
Keywords:
Ó 2013 Elsevier B.V. All rights reserved.
Morpholine
Dynamic NMR
Ring inversion
1. Introduction
We have recently reported the use of chalcone derivatives as
corrosion inhibitor of mild steel [11]. It has also been reported that
Chalcones are an important group of natural products belonging
to the flavonoid family [1]. Chalcone derivatives are gaining much
attention in the recent past because of their promising biological as
well as pharmaceutical properties including antibacterial, anti
inflammatory and anticancer activities [2]. Chalcone based anti-
cancer drugs are reported to be devoid of the side effects often
associated with genotoxic effects [3,4]. Ru(II)–DMSO–Cl–chalcone
complexes have been shown recently to have significant effects
on DNA binding and shows topoisomerase II inhibitory activity
[5]. The presence of both electron-donating and electron with-
drawing substituents attached to the aromatic ring of chalcone
derivatives exhibits significant nonlinear optical responses [6].
Further, because of their high extinction coefficient of UV absorp-
tion, chalcone derivatives are reported to be good candidates for
optical applications [7–9]. Chalcone–benzoxaborole hybrid mole-
cules are found to be useful for antitrypanosomal therapies [10].
chalcone derivatives attached by aliphatic spaced chain increases
the antibacterial and antifungal activity [12]. Chalcone based
morpholine derivatives are known to exhibit a broad spectrum of
biological activities and present a great potential for pharmacolog-
ical applications such as anti-ulcer, herbicidal, anti-bacterial,
analgesic, sedative, anti-phlogistic, and virucidel agents [13].
Carbon substituted morpholines are reported to be effective for
the treatment of panic disorder, deficit disorder, deficit hyperactiv-
ity disorder [14,15]. N-substituted morpholines are used in the
treatment of inflammatory diseases, asthma and migraine [16].
N-substituted morpholines are also reported to show activity like
anti-emetics, platelet aggregation inhibitors and bronchodialators
[17]. Studies on the energetic of N-substituted morpholine
derivatives are highly important in understanding the biological
activities and designing new drugs. In the present study, we
describe the synthesis and spectral characterization of a novel
chalcone based, aliphatic chain spaced, morpholine derivative
namely,
(E)-1-(biphenyl-4-yl)-3-(4-(5-morpholinopentyloxy)
⇑
Corresponding author. Tel.: +91 044 22358660.
E-mail address: kathsubramanian@yahoo.com (K. Subramanian).
phenyl) prop-2-en-1-one (abbreviated as BMPP, shown in Fig. 1).
0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2013.02.029

R. Baskar et al. / Journal of Molecular Structure 1040 (2013) 90–97
91
Fig. 1. Schematic drawing of BMPP (atom numbering is given for better understanding in discussions).
Scheme 1. Synthetic route to BMPP.
The stereo dynamics of the conformational interconversions of the
morphline moiety have also been examined by means of dynamic
NMR spectroscopy.
2.3.1. (E)-1-(biphenyl-4-yl)-3-(4-(5-bromopentyloxy)phenyl)prop-2-
en-1-one
In a 100 ml round-bottomed flask, 4-[(1E)-3-(biphenyl-4-yl)bu-
ta-1,3-dien-1-yl]phenol (1 g, 3.3 mmole), anhydrous potassium
carbonate (.92 g, 6.6 mmole), freshly distilled acetonitrile (30 ml)
and 1,5-dibromopentane (1.8 ml, 13.26 mmole) were placed. The
mixture was refluxed at 70 °C for 12 h and the resulting solution
was cooled down to room temperature, washed with large amount
of water and then extracted using ethyl acetate. The organic layer
was washed with brine solution and dried over anhydrous sodium
sulfate. Solvents present in the resulting solution were removed
through vacuum and further purified by column chromatography.
The final product obtained was a pale yellow colored solid; Yield:
76%. m.p.: 110 °C. 1H NMR (500 MHz, CDCl3) d ppm 1.67 (m,
J = 7.5 Hz, 2H), 1.90 (m, J = 8.0 Hz, 2H), 1.98 (m, J = 7.0 Hz, 2H),
3.47 (t, J = 6.5 Hz, 2H), 4.05 (t, J = 6.5 Hz, 2H), 6.96 (d, J = 8.5 Hz,
2H), 7.43 (t, J = 7.5 Hz, 1H), 7.49 (d, J = 15.5 Hz, 1H), 7.50 (t,
J = 7.5 Hz, 2H), 7.64 (d, J = 9.0 Hz, 2H), 7.65 (d, J = 7.0 Hz, 2H),
7.75 (d, J = 8.5 Hz, 2H), 7.84 (d, J = 16.0 Hz, 1H), 8.12 (d, J = 8.5 Hz,
2H), 13C NMR (126 MHz, CDCl3) d ppm 24.81, 28.36, 32.45, 33.53,
67.77, 114.93, 119.66, 127.25, 127.30, 127.62, 128.16, 128.96,
2. Experimental
2.1. Materials and methods
1,5-Dibromopentane, potassium carbonate, triethylamine, and
morpholine were purchased from Merck, and used without further
purification. Solvents were purified and dried according to stan-
dard procedure [18]. The starting material 4-[(1E)-3-(biphenyl-4-
yl)buta-1,3-dien-1-yl]phenol is prepared from biphenyl using a
two step protocol as described earlier [19].
2.2. Physical measurements
The infrared spectra were recorded on a Perkin Elmer Spectrum
One instrument in the frequency range of 4000–450 cmꢀ1, using
KBr pellet method. Mass spectra were recorded using JEOL GC
MATE spectrometer in the EI mode. NMR spectra were recorded
in CDCl3 solvent on a Bruker Avance III 500 MHz instrument, using
TMS as an internal reference standard. The DEPT135 spectrum was
recorded on standard manner h = 135 pulse program. Gradient en-
hanced 2D COSY, HSQC, HMBC and NOESY spectra were recorded
using the standard pulse programs from Bruker. Dynamic NMR
measurements were carried out in CD2Cl2 solvent using Bruker
B-VT 3200 model VT accessory with digital temperature controller.
The temperature range of 298–223 K was used for the dynamic
NMR investigations. The low temperature calibration was done
using a solution of 4% CH3OH in CD3OD and the low temperature
measurements were estimated to be accurate to 0.2 K.
Table 1
Infrared spectral data (cmꢀ1) for BMPP.
Vibrations
C@O ( –b unsaturated)
CAH (aromatic)
CAO (morpholine)
Wavenumber, mꢀ1 (cmꢀ1
)
Mode
a
1650 (s)
3031 (w)
1219 (m)
1630 (m)
1456 (m)
2950, 2923, 2866 (s),
1376 (w)
Stretching
Stretching
Stretching
Stretching
Stretching
Stretching
Bending
C@C (
C@C
aꢀb unsaturated)
CAH (aliphatic methyl)
C@O
3433 (m)
Overtone
C@C (vibration)
CAH (aliphatic methyl)
ACAOAC
(Bending)
Out of bending
Stretching
Stretching
Bending
Stretching
Stretching
Stretching
740–866
1293
2.3. Synthesis
ACANA
1116 (s)
1570 (s)
1253 (m)
1176 (m)
1033 (m)
ACAC
ACAOA
AOACA
The Synthetic route to BMPP is provided in Scheme 1. The com-
pound BMPP is synthesized from 4-[(1E)-3-(biphenyl-4-yl)buta-
1,3-dien-1-yl] phenol, using a two step protocol (19). The details
of each step are given in the following section.
(s)-Strong; (m)-medium; (w)-weak.

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R. Baskar et al. / Journal of Molecular Structure 1040 (2013) 90–97
Fig. 2a. 500 MHz 1H NMR spectrum of the compound in CDCl3 at 298 K.
Fig. 2b. 125 MHz 13C NMR spectrum of the compound in CDCl3 at 298 K.
Fig. 2c. DEPT-135 spectrum of the compound in CDCl3 at 298 K.
129.04, 130.28, 137.24, 140.03, 144.64, 145.311, 161.13, 189.97. IR
(KBr, cmꢀ1) 732, 1029, 1170, 1216, 1422, 1474, 1601, 1647, 2857,
1942, 3055, 3440.
amine (0.7 ml, 0.5 mmole) was added slowly followed by morpho-
line (0.21 ml, 0.249 mmole). Stirring was continued further for
48 h and the solution was poured in to beaker containing ice cold
water. The yellow solid obtained was separated by filtration and
purified by column chromatography. The final product obtained
was a yellow colored solid; Yield: 72%. m.p.: 130 °C. 1H NMR
(500 MHz, CDCl3) d ppm 1.50 (m, J = 5.5 Hz, 2H, H5), 1.58 (m,
J = 7.0 Hz, 2H, H4) 1.83 (m, J = 6.5 Hz, 2H, H6), 2.37 (t, J = 8.0 Hz,
2H, H3), 2.45 (s, 4H, H2), 3.72 (t, J = 5.0 Hz, 4H, H1), 4.01 (t,
2.3.2. (E)-1-(biphenyl-4-yl)-3-(4-(5-
morpholinopentyloxy)phenyl)prop-2-en-1-one (BMPP)
To a stirred solution of (E)-1-(biphenyl-4-yl)-3-(4-(5-brom-
opentyloxy)phenyl)prop-2-en-1-one (112 mg, 0.249 mmole) in
N,N-dimethyformamide (15 ml) at room temperature, triethyl-

R. Baskar et al. / Journal of Molecular Structure 1040 (2013) 90–97
93
Fig. 5. Partial 1HA13C HMBC spectrum of BMPP in CDCl3 at 298 K.
Fig. 3. 1HA1H COSY spectrum of BMPP in CDCl3 at 298 K.
J = 6.5 Hz, 2H, H7), 6.92 (d, J = 9.0 Hz, 2H, H9), 7.40 (t, J = 7.5 Hz, 1H,
22), 7.48 (d, J = 15.5 Hz, 1H, H12), 7.49 (t, J = 7.5 Hz, 2H, H21), 7.61
(d, J = 9.0 Hz, 2H, H10), 7.65 (d, J = 7.0 Hz, 2H, H20), 7.72 (d,
J = 8.5 Hz, 2H, 17), 7.82 (d, J = 15.5 Hz, 1H, H13), 8.10 (d,
J = 8.0 Hz, 2H, H16), 13C NMR (126 MHz, CDCl3) d ppm 23.98 (C5),
melting point of the compound was 130 °C. The compound was
found to be soluble in chloroform, dichloromethane, dimethyl sulf-
oxide, dimethyl formamide, ethyl acetate and acetone. The mass
spectral data was in accordance with the calculated molecular
weight of 455.6 amu.
H
H
0
0
26.26 (C4), 29.07 (C6), 53.77 (C2, C2 ), 58.94 (C3), 66.96 (C1, C1 ),
0
0
67.96 (C7), 114.91 (C9, C9 ), 119.61 (C12), 127.25 (C17, C17 ), 127.29
3.1. IR spectral assignment
0
0
(C20, C20 ), 127.52 (C11), 128.16 (C22), 128.96 (C21, C21 ), 129.04
0
0
(C16, C16 ), 130.27 (C10, C10 ), 137.24 (C15), 140.03 (C19), 144.69
(C13), 145.31 (C18), 161.24 (C8), 190.00 (C14). IR (KBr, cmꢀ1) 740,
866, 1010, 1033, 1116, 1176, 1219, 1293, 1423, 1456, 1570,
1650, 2866, 2923, 2950, 2923, 2866, 3031, 3433.
The important vibrational frequencies observed for BMPP are
listed in Table 1. The characteristic carbonyl stretching vibration
3. Results and discussion
The purified compound was yellow in color and analytical data
were in good agreement with molecular formula, C30H33O3N. The
Fig. 4. 1HA13C HSQC spectrum of BMPP in CDCl3 at 298 K.
Fig. 6. NOESY spectrum of BMPP in CDCl3 at 298 K with a mixing time of 300 ms.

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R. Baskar et al. / Journal of Molecular Structure 1040 (2013) 90–97
Table 2
1H and 13C NMR data, 1HA1H COSY, 1HA13C HSQC and 1HA13C HMBC correlations of BMPP.
Carbon number
Chemical shift (ppm)
1HA1H COSY
1HA13C HSQC
(1J)
1HA13C HMBC
(3J)
dH
dC
66.96
53.77
58.94
26.26
23.98
C1,C10
C2,C20
C3
C4
C5
C6
C7
C8
C9,C90
C10,C100
C11
C12
C13
C14
C15
C16,C160
C17,C170
C18
3.72 (t, J = 5.0 Hz, 4H)
2.45 (s, 4H)
H2
H1
H4
H3
H6
H5,H7
H6
–
C10
H9
–
C13
C12
–
69.96
53.77
58.94
26.26
23.98
29.07
67.96
–
114.91
130.27
–
119.61
144.69
–
–
–
–
–
–
–
–
2.37 (t, J = 8.0 Hz, 2H)
1.58 (m, J = 7.0 Hz, 2H)
1.50 (m, J = 5.5 Hz, 2H)
1.83 (m, J = 6.5 Hz, 2H)
4.01 (t, J = 6.5 Hz, 2H)
–
6.92 (d, J = 9.0 Hz, 2H)
7.61 (d, J = 9.0 Hz, 2H)
–
29.07
67.96
161.24
114.91
130.27
127.52
119.61
144.69
190.00
137.24
129.04
127.25
145.31
140.03
127.29
128.96
128.16
67.96(C7) 130.27(C10)
–
–
114.91(C9) 144.69(C13)
–
–
119.61(C12) 129.04(C16)
127.25(C17)
–
–
129.04(C16) 127.29(C20)
127.25(C17) 128.96(C21)
–
–
–
7.48 (d, J = 15.5 Hz, 1H)
7.82 (d, J = 15.5 Hz, 1H)
–
–
–
–
8.10 (d, J = 8.0 Hz, 2H)
7.72 (d, J = 8.5 Hz, 2H)
–
C17
C16
–
129.04
127.25
–
C19
–
–
–
C20,C200
C21,C210
C22
7.65 (d, J = 7.0 Hz, 2H)
7.49 (t, J = 7.5 Hz, 2H)
7.40 (t, J = 7.5 Hz, 1H)
C21
C20
–
127.29
128.96
128.16
of
a
–b-unsaturated ester group occurred at 1650 cmꢀ1
.
The
between 820 cmꢀ1 and 1010 cmꢀ1 were assigned to be the charac-
teristic CAH out of plane or wagging vibrations. The CAO stretch-
ing vibration of morpholine moiety is observed 1219 cmꢀ1, while
the medium band at 3433 cmꢀ1 is attributed to the C@O overtone
of the chalcone moiety. The CAN stretching (1116 cmꢀ1) and CAN
bending (1570 cmꢀ1) modes of vibrations were also identified.
aromatic CAH stretching signal of the compound appeared at
3031 cmꢀ1 while the aliphatic methyl stretching frequency
appeared at 2923 cmꢀ1. The vibrational stretching frequency of
CAOAC appeared at 1293 cmꢀ1. Alkyl CAH bending vibration ap-
peared at 1423 cmꢀ1. The vibrational bands observed at regions
Fig. 7. Temperature-dependent 1H NMR spectra of BMPP.

R. Baskar et al. / Journal of Molecular Structure 1040 (2013) 90–97
95
Table 3
3.2. NMR spectral assignments
Kinetic data of BMPP derived from dynamic NMR measurements.
One dimensional 1H, 13C and DEPT-135 NMR spectra of the
BMPP in CDCl3 are shown in Figs. 2a, 2b and 2c respectively.
From these spectra, characteristic 1H and 13C resonances corre-
sponding to the chalcone, alkyl spacer and morpholine moieties
were identified, and further confirmed by advanced 2D NMR stud-
ies. Unequivocal assignment of assignments for these spin systems
were obtained using Gradient enhanced COSY and HSQC experi-
ments with additional data obtained from long-range 1HA13C cor-
relation experiments and NOESY experiments. Two dimensional
correlation spectroscopy (COSY) experiment is employed to estab-
lish connectivity between all directly coupled protons as illustrated
in Fig. 3. The important through bond correlations derived from
sꢀ1
Gꢁc (Kcal molꢀ1)
11.08
Tc (K)
D
m
(Hz)
Kc
(
)
D
248
405.6
884.43
COSY are those between H1 M H2, H3 M H4, H4 M H5, H5 M H6,
H6 M H7, H9 M H10 12 M H13 16 M H17 20 M H21 and
21 M H22. The one bond 1HA13C connectivity between all carbons
,
H
,
H
,
H
H
directly attached to protons was established from the heteronu-
clear single quantum coherence (HSQC) measurement using an
evolution time of 17.2 ms (Fig. 4). Long range 1HA13C correlations
were obtained from the heteronuclear multiple bond correlation
(HMBC) experiment, employing an evolution time of 65 ms. HMBC
Fig. 8. (A) Expanded portion of dynamic NMR data of BMPP and (B) schematic of ring inversion of morpholine moiety.

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R. Baskar et al. / Journal of Molecular Structure 1040 (2013) 90–97
was particularly useful for the assignments of ACO, ACN and the
quaternary carbons, as illustrated in Fig. 5. The linkage between
the chalcone moiety and the alkyl spacer and also between the al-
kyl spacer and the morpholine moiety were established from
HMBC by deriving long range multiple bond correlation between
C8 M H7, C3 M H2 and C2 M H3. The NOESY correlation H9 M H7,
further conformed the linkage between the chalcone moiety and
the alkyl spacer (Fig. 6).
in well separated signals corresponding to non-equivalent protons
(i.e., H1a, H1e, H2a and H2e). At 223 K, equatorial protons appeared
as broad doublets at d2.69 (2Jae = 10.8 Hz) and 3.74 (2Jae = 10.56 -
Hz). The axial protons appeared at d2.03 (3Jaa = 10.5 Hz) and 3.50
(3Jaa = 11.3 Hz). Thus, at lower temperature, the system is behaving
like AB2 rather than AA0XX0 (i.e., a triplet for axial proton and a dou-
blet for equatorial proton). Similar dynamic behavior is reported
earlier for other morpholine derivatives also [20].
The complete assignment of BMPP is given in Table 2. Important
3JHAH coupling constants derived are also given. The chair confor-
mation of the morpholine moiety is established from the observa-
tion of through space NOE correlation between H2 M H4 in the
room temperature NOESY spectrum (Fig. 6) recorded with a mixing
time of 300 ms.
The chemical shift difference (Dm) is obtained by taking the dif-
ference between the midpoint of the doublet and the middle point
of a triplet. Barriers to ring inversion for the BMPP is calculated
p
using the approximation equation kc =
p
D
mc
/
2 and
G–c =19.14 Tc
D
G–c at Tc is
determined by the Eyring equation at Tc [(
D
(10.32 + log Tc/kc)] [12]. Kinetic parameters estimated, based on
dynamic NMR measurements, are given in Table 3. The calculated
barriers to ring inversion of BMPP are found to be 11.08 Kcal molꢀ1
at 500 MHz frequency. The free energy of activation is in reason-
able agreement with the values obtained [21].
3.3. Dynamic NMR studies
The conformational behavior of morpholine based systems has
attracted special attention because of their occurrence in many
complex natural and synthetic compounds of pharmacological
interest [20]. Dynamic NMR spectroscopy has been employed as
a vital tool in studying the stereo dynamics of the conformational
interconversions of the morphline moiety [21]. In the chair confor-
mation of the morpholine moiety, the axial and equatorial protons,
being in slightly different chemical environments, are expected to
resonate at different frequencies. Hence one should expect to see
two signals each in the 1H NMR spectrum. However, in the 1H
NMR recorded at room temperature (Fig. 1a), only one signal each
is seen for protons attached to both C1 and C2 positions. This is be-
cause of the rapid ring interconversion of morpholine ring [21]. At
room temperature, significant ring inversion of the morpholine
moiety is occurring and as a result of this, the interconversion be-
The stereo dynamics of morphine ring inversion has been a very
interesting topic of research in recent years [12]. When no substi-
tuent is present on the morpholine nitrogen, ring inversion is too
fast to be monitored by dynamic NMR studies. However the barrier
to ring inversion for N-methyl morpholine is reported to be 11.
5 kcal molꢀ1. From a study on the effect of substituents on the ring
interconversion of morpholine compounds, it is documented that
sterric phenomena slow down the conformational interconversion
[21,22]. For example, bulkier group attached to nitrogen strongly
increases the barrier to the ring inversion relative to an alkyl group
[21]. The rate of conformational interconversion of morpholine
ring also depends on the type of substituent. The equatorial and ax-
ial protons are observed even at room temperature, when bulkier
substituents are present in morpholine ring [22].
tween the axial and equatorial protons (i.e., H1a M H1e and H2a
M H2e) becomes inaccessible in the NMR time scale. Hence only
one signal each is observed for each site.
-
It is also interesting to note that the even though slow, the
interconversion is still occurring at temperature as low as 223 K.
This is manifested by the NOESY spectrum recorded at 223 K. Gen-
erally, in the 2D NOESY spectrum, cross peaks arising from ex-
change phenomena have the same phase as the diagonal, while
NOE cross peaks indicating spatial proximity have opposite phase
In order to find the stereo dynamic nature of the morpholine
moiety in BMPP, 1H NMR spectra of BMPP has been measured at
temperatures sufficiently low for the ring-inversion process to ap-
pear slow. Since the solubility of BMPP in CDCl3 solvent was very
low as at lower temperatures, CD2Cl2 was used as solvent for the
low temperature dynamic NMR measurements. The 500 MHz 1H
dynamic NMR spectra of BMPP recorded in CD2Cl2 solvent at differ-
ent temperatures ranging from 298 K to 223 K are shown in Fig. 7.
At room temperature (298 K), the ring protons of the morpho-
line moiety (ANCH2 and AOCH2) appeared as two separate sets
of signals, one broad triplet at d 2.39 and a clear triplet at d 3.6 with
an intensity ratio of 4:4. The proton signals of the ANCH2 protons
are strongly broadened both pointing already to a dynamic process
near to the slow exchange range. On gradual cooling, signals of the
ANCH2 and AOCH2 protons of the morpholine ring gets broadened
and decoalesced at 248 K into two broadened signals each. Appar-
ently, on further cooling to 223 K, these signals formed pairs of
clear doublets and triplets as shown in the expanded portion of
the dynamic NMR spectra of BMPP in (Fig. 8A).
A schematic representation of the ring inversion of two chair
conformations of morpholine moiety is presented in Fig. 8B. At
room temperature (298 K), there is significant ring inversion of
the morpholine moiety. As
between the axial and equatorial protons (i.e., H1a M H1e and
2a M H2e) becomes inaccessible in the NMR time scale and only
a result of this, interconversion
H
one signal is observed for each site (Fig. 8A). As the temperature
is lowered, the rate of ring interconversion slows down, and signals
corresponding to the axial and equatorial protons of the morpho-
line moiety are separated out. At about 248 K, the decoalescence
temperature is observed. After the decoalescence temperature,
the ring inversion approaches the slow exchange regime, resulting
Fig. 9. Portion of the NOESY spectrum of BMPP. The spectrum was acquired at
233 K with a 300 ms mixing time. The exchange cross peak between H1a M H1e, and
between H2a M H2e are marked with corresponding one dimensional spectra at the
top and to the left.

R. Baskar et al. / Journal of Molecular Structure 1040 (2013) 90–97
97
to the diagonal [20]. The existence of exchange cross peaks
References
between the H1a M H1e and also H2a M H2e, protons of the morpho-
line moiety in Fig. 9 illustrates that conformational interconversion
occur even at 223 K. Exchange spectroscopy is often employed to
establish the existence of equilibrium between two enantiomeric
species [20].
Another interesting feature of dynamic NMR data is that neither
the chemical shift nor the line width of signals other than those of
the morpholine ring protons changes as the temperature is
lowered. This means that the entire dynamics of the BMPP mole-
cule depends on the stereodynamics of the morpholine moiety.
[1] Koneni V. Sashidhara, Abdhesh Kumar, Manoj Kumar, Jayanta Sarkar, Sudhir
Sinha, Bioorg. Med. Chem. Lett. 20 (2004) 7205.
[2] Z. Nowakowska, B. Kedzia, G. Schroeder, Eur. J. Med. Chem. 43 (2008) 701.
[3] R.J. Anto, K. Sukumaran, G. Kutton, M.N.A. Rao, V. Subbraraju, R. Kuttan, Cancer
Lett. 97 (1995) 33.
[4] K.L. Lahtchev, D.I. Batovska, St.P. Parushev, V.M. Ubiyvovk, A.A. Sibirny, Eur. J.
Med. Chem. 43 (2008) 2220.
[5] Ruchi Gaur, Lalan Mishra, Inorg. Chem. 51 (2012) 3059.
[6] M.P. Cockerham, C.C. Frazier, S. Guha, E.A. Chauchard, Appl. Phys. B 53 (1991)
275.
[7] B.K. Sarojinia, B. Narayanab, B.V. Ashalathab, J. Indirac, K.G. Lobo, J. Cryst.
Growth 95 (2006) 54.
[8] P. Poornish, S. Shettigar, G. Umesh, K.B. Manjunatha, K.P. Kamath, B.K. Sarojini,
B. Narayana, Opt. Mater. 31 (2009) 854.
[9] R. Nithya, N. Santhanamoorthi, P. Kolandaivel, K. Senthilkumar, J. Phys. Chem.
A 115 (2011) 6594.
4. Conclusion
[10] Zhitao Qiao, Qi Wang, Fenglong Zhang, Zhongli Wang, Tana Bowling, Bakela
Nare, Robert T. Jacobs, Jiong Zhang, Dazhong Ding, Yangang Liu, Huchen Zhou,
J. Med. Chem. 55 (2012) 3553.
[11] R. Baskar, M. Gopiraman, D. Kesavan, Ick Soo Kim, K. Subramanian, Ind. Eng.
Chem. Res. 51 (2012) 3966.
[12] Ali Reza Modarresi-Alam, Homeyra Alsadat Amirazizi, Hajar Bagheri, Hamid-
Reza Bijanzadeh, Erich Kleinpeter, J. Org. Chem. 74 (2009) 4740.
[13] V.K. Ahluwalia, M. Chopra, R. Chandra, J. Chem. Res. 125 (2000) 162.
[14] E.H. Pommer, Pestic. Sci. 15 (1984) 285.
[15] E.H.F. Wong, M.S. Sonders, S.G. Amera, P.M. Tinholt, M.F.P. Piercey, W.P.
Hoffmann, D.K. Hyslop, S. Franklin, R.D. Porsolt, A. Bonsignori, N. Carfagna, R.A.
McArthur, Biol. Psychiatr. 47 (2000) 818.
[16] C. Dugave, L. Demange, Chem. Rev. 103 (2003) 2475.
[17] A. Arrieta, D. Oteagui, A. Zubia, F.P. Cossio, A. Diaz-Ortiz, A. Hoz, A. Herrero, P.
Prieto, C. Foces-Foces, J.L. Pizarro, M.I. Arriortua, J. Org. Chem. 72 (2007) 4313.
[18] A.I. Vogel, Textbook of Practical Organic Chemistry, fifth ed., Longman, London,
1989.
[19] R. Baskar, K. Subramanian, Spectrochim. Acta Part A 79 (2011) 1992.
[20] Alan R. Katritzky, Novruz G. Akhmedov, Hongfang Yang, Dennis Hall, Magn.
Reson. Chem. 43 (2005) 673.
In this present study, we have synthesized a novel chalcone
based N-substituted morpholine derivative, and their structure
has been confirmed by different 1D and 2D NMR techniques. The
1H NMR spectra of this compound as a function of temperature
were investigated. The six membered heterocyclic ring of the
morpholine moiety adopts a chair conformation and a process of
rapid interconversion which averages the NMR signals at room
temperature is observed. On freezing to 248 K, both proton signals
in the morpholine moiety of BMPP show the expected decoales-
cence effects and well separated signals were observed at 223 K.
The calculated free energy of activation is comparable with the
literature data.
Acknowledgements
[21] Lodovico Lunazzi, Daniele Casarini, Mauro A. Cremonini, Tetrahedron 47
(1991) 7465.
[22] Raul Hernandez-Altamirano, Violeta Y. Mena-Cervantes, Sandra Perez-
Miranda, Francisco J. Fernandez, Cesar Andres Flores-Sandoval, Victor
Barba, Hiram I. Beltran, Luis S. Zamudio-Rivera, Green Chem. 12 (2010) 1036.
The authors are grateful to acknowledge SAIF, IIT-Madras
for supporting in all the spectroscopic studies. We thank
Dr. V. Kesavan, Department of Bio-technology, IIT-Madras for his
support in this work.