Dynamic NMR and computational study of 5,5-dimethyl-3,4-di-p-tolyl-2- cylopenten-1-one

Article abstract of DOI:10.1016/j.saa.2011.05.060

The restricted rotation of p-tolyl moiety in 5,5-dimethyl-3,4-di-p-tolyl-2- cyclopenten-1-one was studied by variable temperature NMR spectroscopy at a temperature range of 218-368 K. A free rotation, in NMR time scale, was observed at temperatures higher

Full text of DOI:10.1016/j.saa.2011.05.060

Spectrochimica Acta Part A 79 (2011) 1798–1802
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Dynamic NMR and computational study of
5,5-dimethyl-3,4-di-p-tolyl-2-cylopenten-1-one
Katayoun Marjania, Mohsen Mousavib,∗, Hossein Taherpour Nahzomic, Omid Arazia, Reza Jafaria
a Faculty of Chemistry, Tarbiat Moalem University, 49 Mofateh Avenue, 15614 Tehran, Iran
b Department of Chemistry, Islamic Azad University, Saveh Branch, P.O. Box 39187/366, Saveh, Iran
c Department of Chemistry, Payame Noor University (PNU), Talesh, P.O. Box 43711-49111, Guilan, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The restricted rotation of p-tolyl moiety in 5,5-dimethyl-3,4-di-p-tolyl-2-cyclopenten-1-one was studied
by variable temperature NMR spectroscopy at a temperature range of 218–368 K. A free rotation, in
NMR time scale, was observed at temperatures higher than 368 K; while, the rotation froze below 248 K.
Received 9 October 2010
Received in revised form
24 December 2010
From dynamic NMR analysis, the Arrhenius energy of activation ꢀG‡ was calculated as 56.37 kJ mol−1
.
Accepted 20 May 2011
The experimental results were confirmed by theoretical calculation using the density functional theory
method B3LYP with basis sets, 6-31G and 6-31+G.
Keywords:
Cyclopentenone
© 2011 Elsevier B.V. All rights reserved.
Dynamic NMR
Density functional theory
Rotation barrier
Theoretical calculation
Variable-temperature NMR
1. Introduction
restricted intramolecular rotation [4]. For example, the rotational
barriers are often measured by dynamic NMR methods, because
Hindered rotation about the C–C bond is an on-going topic in
conformational stereochemistry that has attracted the interest of
many investigators [1–5]. It is well accepted that C–C single bond
rotation is usually fast, because it does not involve any reduc-
tion in orbital overlapping. However, the rotational barrier (ꢀG‡)
increases with structural factors, where bulky substituents inter-
acted with each other [6]. It is important to fully understand how
structural and environmental factors control the associated kinet-
ics and thermodynamics. Atropisomeric compounds [2,7,8] and
synthetic molecular machines [1,9] are some important results
of hindered rotation phenomena. Furthermore, to understand
biological mechanisms of bioactive compounds, it is necessary
to investigate their minimum energy conformations and their
intramolecular flexibilities [10].
at low temperatures, NMR signals for the different rotamers can be
observed, and the rotational barrier (ꢀG‡) can be easily measured at
signal coalescence [2–7,12,13]. In this paper, we report the dynamic
1H NMR and computational study of hindered rotation of an aryl
substituent in a cyclopentenone derivative.
2. Experimental
2.1. General
4-Hydroxy-5,5-dimethyl-3,4-di-p-tolyl-2-cyclopenten-1-one,
1, was obtained as described earlier [14]. Other chemicals and
solvents were obtained from Merck and used as received. 1H NMR
spectra were recorded on a Bruker Avance-300 MHz spectrometer
employing tetramethylsilane as an internal reference. IR spectra
were recorded with a Perkin-Elmer 843 spectrometer. Mass
spectra were recorded on a Shimadzu GC/MS QP1100 EX model.
Restricted rotation of sterically hindered groups in a large
number of molecules has been studied by various spectroscopic,
analytical, and computational studies [2,9,11,12]. Dynamic NMR
studies have been extensively used to explore the kinetics and
thermodynamics of the stereodynamic processes, occurring due to
2.2. Preparation of
2,2-dimethyl-1,5-di-p-tolyl-4-cyclopenten-1,3-diol, 2
To
a solution of 4-hydroxy-5,5-dimethyl-3,4-di-p-tolyl-2-
∗
Corresponding author. Tel.: +98 255 2241511; fax: +98 255 2240111.
E-mail addresses: drmousavi@hotmail.com, moooosavi@yahoo.com
cyclopenten-1-one, 1 (1 g, 3.27 mmol) in methanol (30 ml) was
(M. Mousavi).
added an excess of NaBH4. The mixture was stirred at room
1386-1425/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2011.05.060

K. Marjani et al. / Spectrochimica Acta Part A 79 (2011) 1798–1802
1799
CH3
CH3
CH3
H3C
H3C
H3C
CH3
H3C
HO
O
HO
(a)
(b)
(c)
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
OH
CH3
O
2
3
4
1
Scheme 1. The chain procedure for synthesis of 1,5,5-trimethyl-3,4-di-p-tolyl-1,4-cyclopentadiene 4. Reagents and conditions: (a) NaBH4/MeOH/RT/3 h; (b) conc.
HCl/EtOH/80 ◦C/3 h; (c) CH3I/anhydrous diethylether/RT/7 day.
19
CH3
CH3
15
16
12
H3C
17
18
10
H3C
14
9
11
13
4
H
H
H
H
H
8
H
3
6
21
7
5
H
H
2
CH3
CH3
H
H
20
H
1
H
O
O
Scheme 2. The chemical structure, atom numbering and conformational equilibrium of 3.
Fig. 1. The variable temperature 1H NMR spectra of 3 (a) from 218 to 318 K in acetone-d6; (b) from 328 to 368 K in DMSO-d6.
temperature for 3 h. The solvent was then removed on a rotary
2.3. Preparation of
evaporator. The organic layer was extracted with diethyl ether
(30 ml), washed with water and dried over Na2SO4. The solvent
evaporation in vacuo gave 2 (0.8 g, 79.5%). Mp 54–56 ◦C. IR (KBr) (ꢁ
max, cm−1): 3462 (br, OH), 1522 (m, C C). 1H NMR (acetone-d6):
ı 0.51 (3H, s, CH3), 1.28 (3H, s, CH3), 2.21 (3H, s, CH3), 2.25 (3H, s,
CH3), 3.99 (1H, d, J = 5.9 Hz, OH), 4.10 (1H, s, OH), 4.71 (1H, dd, J = 2.3,
5.9 Hz, CH), 6.28 (1H, d, J = 2.3 Hz, CH), ı 6.94 (2H, d, J = 8, C6H4), 6.99
(2H, d, J = 8, C6H4), 7.23–7.28 (4H, dd, J = 15, 8.2). MS (m/z, %): 308
(M+, 33), 119 (100), 91 (83), 65 (41), 45 (66).
5,5-dimethyl-3,4-di-p-tolyl-2-cyclopenten-1-one, 3
To a stirred solution of 2 (1 g, 3.25 mmol) in ethanol (20 ml)
was added conc. HCl (5 ml). The mixture was refluxed for 3 h, then
cooled and extracted with diethyl ether (30 ml). The organic layer
was washed with water and dried over Na2SO4. Solvent evapora-
tion in vacuo gave 3 (0.65 g, 69%). Mp 102–104 ◦C. IR (KBr) (ꢁ max,
cm−1): 1689 (s, C O), 1601 (m, C C). 1H NMR (acetone-d6, 25 ◦C):
ı 0.65 (3H, s, CH3), 1.33 (3H, s, CH3), 2.28 (3H, s, CH3), 2.32 (3H, s,

1800
K. Marjani et al. / Spectrochimica Acta Part A 79 (2011) 1798–1802
Table 1
b
Calculated energies for ground state and transition state structures of 3.a,
.
d
Molecule
Eelec
ZPEc
E0
ꢀE0 (calculated)e
ꢀG‡ (experimental)
6-31G
6-31+G(d,p)
6-31G
6-31G
6-31+G(d,p)
Ground state
Transition state
−888.508198
−888.485392
−888.784979
−888.763448
0.375040
0.375477
−888.133158
−888.109915
−888.409939
−888.387971
−1
0.021968 h ≡ 57.68 kJ mol56.37 kJ mol−1
a
All calculations were performed with B3LYP method.
All energies are in hartree unless otherwise mentioned.
Unscaled.
E0 = Eelec + ZPE.
We used the E0 values with larger basis set.
b
c
d
e
recrystalized from hexane. Mp 119–121 ◦C. IR (KBr) (ꢁ max, cm−1):
1578 (w, C C). 1H NMR (acetone-d6): ı 1.08 (6H, s, CH3), 1.94 (3H,
d, J = 1.6 Hz, CH3), 2.22 (3H, s, CH3), 2.33 (3H, s, CH3), 6.33 (1H, q,
J = 1.6 Hz, CH), 6.95 (2H, d, J = 7.8, C6H4) 7.02 (2H, d, J = 8.2, C6H4),
7.09 (2H, J = 8.2, C6H4), 7.16 (2H, d, J = 7.8, C6H4). MS (m/z, %): 288
(M+, 100), 243 (35), 165 (25), 115 (20), 91 (20).
CH3), 4.27 (1H, d, J = 1.1 Hz, CH), ı 6.68 (1H, d, J = 1.1 Hz, CH), 7 (2H,
br), 7.11 (2H, d, J = 8.1), 7.43 (2H, d, J = 8.1). MS (m/z, %): 290 (M+,
85), 115 (100), 91 (57), 42 (42).
2.4. Preparation of
1,5,5-trimethyl-3,4-di-p-tolyl-1,3-cyclopentadiene, 4
To a solution of 3 (1 g, 3.47 mmol) in anhydrous diethyl ether
(100 ml), was added an excess of CH3MgI/Et2O. The mixture was
stirred at room temperature for 7 days; then poured into cold water
(50 ml). The organic layer was separated, washed with water, dried
on Na2SO4. The solvent was evaporated in vacuo. Chromatogra-
phy on silica gel plate (hexane, 20 ml) gave 4 (0.85 g, 85.6%), which
2.5. Computational methods
The calculations were performed by the DFT method employing
the Becke3-Lee-Yang-Par B3LYP exchange correlation functional in
combination with the 6-31G and 6-31+G (d,p) basis sets using the
Gaussian 98 program [15]. Analytical frequencies were determined
Fig. 2. B3LYP/6-31G optimized structures of 3 (a) ground state; (b) transition state.
Fig. 3. The aromatic region of 1H NMR spectra of 3 (a) from 218 to 318 K in acetone-d6; (b) from 328 to 368 K in DMSO-d6.

K. Marjani et al. / Spectrochimica Acta Part A 79 (2011) 1798–1802
1801
at the B3LYP/6-31G level of theory to confirm the nature of each
stationary point and to provide zero-point energies (ZPEs).
ring (C13–C18) is frozen with respect to the NMR time scale; so
its protons become non-equivalent because of their different envi-
ronments. Therefore, the 1H NMR spectrum at 218 K exhibits four
distinct doublets centered at 7.45, 7.18, 6.94 and 6.57 ppm. At
higher temperatures, these signals become broadened until their
splitting become disappeared at 278 K. Under fast exchange, the
protons can no longer be distinguished by NMR spectroscopy. So
at 288 K, the four signals coalescence to a broad signal. This signal
is sharpened at higher temperatures until splits at 368 K to form
two distinct doublets, centered at 7.04 and 6.94 ppm. The dynamic
NMR behavior of 3 indicates that the phenyl ring gradually over-
comes the barrier of rotation at 298 K and higher temperatures. A
free rotation, respect to NMR time scale, is achieved at 368 K. The
rate constant (kr), and the free energy of activation (ꢀG‡) for rota-
tion of phenyl ring are calculated from the variable temperature
1H NMR data by following literature equations [28]; kr = 2.22ꢀꢂ,
ꢀG‡ = 19.1Tc [10.32 + log(Tc/kr)] × 10−3 kJ mol−1. From the ꢀꢂ of
153 Hz and the coalescence temperature Tc of 288 K, kr and, ꢀG‡,
were calculated to be 339.66 s−1 and 56.37 kJ mol−1, respectively.
3. Results and discussion
Diphenylcyclopentenones were often prepared via aldol con-
densation of benzil with acetone derivatives in alkaline media.
This procedure was first introduced by Japp [16–18], and was
used for preparation of cyclopentenones [14,19–24]. We have
recently extended Japp’s procedure to the preparation of diaryl-
cyclopentenones [25], and utilized them as starting materials
for the preparation of other synthetic targets. Scheme 1 shows
our procedure for the synthesis of 5,5-dimethyl-3,4-di-p-tolyl-2-
cyclopenten-1-one, 3, and its conversion to 1,5,5-trimethyl-3,4-
di-p-tolyl-1,3-cyclopentadiene, 4. The starting compound, 1, was
prepared by Japp’s procedure [26].
During the work, we encountered an unusual feature in the
1H NMR spectrum of 3. A peak for two aromatic protons was
absent in the room temperature spectrum of 3. There was no doubt
in the structure of product, since it was confirmed by a single
crystal X-ray diffraction analysis, apart from other spectral and
analytical evidences [27]. Furthermore, two related compounds, 2
and 4, presented normal 1H NMR spectra as expected from pro-
posed structures. Therefore, we performed a dynamic NMR study,
followed by a theoretical calculation, to achieve a reasonable under-
standing of the 1H NMR spectra of 3.
3.2. Theoretical calculations
In order to verify the interpretation of experimental results, the
rotational barrier about C4–C13 single bond was calculated using a
computational approach. First, the ground state of 3 was optimized
at B3LYP/6-31G level of theory (Fig. 2a). According to frequency
calculation it has no imaginary frequency, thus, it is a minimum on
the PES.
3.1. Dynamic NMR experiments
The H4–C4–C13–C18 dihedral angle value (for simplification we
call it “D” in the following discussion) is −22.80◦. The distances
between atoms H18A and H21C and also between H14A and H21B
Fig. 1 shows the variable temperature 1H NMR spectra of 3. Due
to the limitations imposed by physical properties of solvents (boil-
ing and melting points), the NMR experiments were performed in
two different solvents, from 218 to 318 in acetone-d6 and from 328
to 368 in DMSO-d6.
˚
˚
are 3.22 A and 2.88 A, respectively (Fig. 2a). Increasing the D value
leads to the corresponding transition state structure (Fig. 2b) which
was then optimized at the same level of theory as the ground
state structure. It has one imaginary frequency, thus it is transi-
tion structure on the PES. The D value for this structure is 70.59◦.
IRC calculation demonstrated that these two structures are related
to each other by rotation about C4–C13 single bond. The distances
between atoms H18A and H21C and also between H14A and H21B
The signal assignments are depicted in the spectra, with num-
bering of protons as indicated in the Scheme 2. The first two signals
at high field, 0.5 and 1.22 ppm, are assigned to the geminal methyl
groups, 20 and 21. The next two signals, 2.19 and 2.25 ppm, corre-
spond to the methyl substituents of p-tolyl moieties, 12 and 19. The
signal at 2.05 ppm and the temperature dependent signal at around
3 ppm correspond to acetone-d5 and HOD impurities, respectively.
Two protons of five-membered ring, 4 and 2, present signals at 4.54
and 6.68 ppm. Four aromatic protons of conjugated p-tolyl, 7, 8, 10
and 11, present two doublets centered at 7.58 and 7.15 ppm, each
integrated for two protons. The aromatic protons of other p-tolyl
moiety, 14, 15, 17 and 18, exhibit temperature dependent signals;
four doublets at 218 K, which are joined to form two doublets at
368 K. There is also a signal overlap below 278 K, between the dou-
blet assigned to protons 8, 10 and that of proton 18.
˚
˚
are 5.36 A and 1.91 A, respectively (Fig. 2b).
It should be mentioned that, because of resource limitation,
performing frequency calculation at B3LYP/6-31+G(d,p) level is
impossible. This limitation is the reason of applying ZPE values at
B3LYP/6-31G level in our calculations.
Table 1 contains some results of optimizations, frequency
and single point energy computations. From this data, the rota-
tional barrier about C4–C13 single bond, ꢀE0, is obtained equal
to 57.68 kJ mol−1, which is in good agreement with the ꢀG‡
calculated from dynamic NMR data (56.37 kJ mol−1). The sup-
plementary information contains the Cartesian coordinates of
optimized geometries of ground state and transition state struc-
tures of 3.
The dynamic NMR behavior of 3, arises from the restricted
rotation of substituted phenyl ring around C(4)–C(13) bond. The
restriction may be best explained by two structures depicted in
Fig. 2. The structure a shows an almost planar cyclopentenone ring,
which imposed an eclipsed conformation for substituents of C(4)
and C(5). This conformation puts a methyl group, C(21), very close
to the phenyl ring, C(13)–C(18). The distance between H(18A) of
4. Conclusion
The dynamic NMR behavior of 3 results from the eclipsed con-
formation of C4–C5, which is imposed by the planar structure of the
cyclopentenone ring. This conformation restricts the rotation of a
p-tolyl moiety at room temperature. The energy associated with the
barrier of rotation was calculated as 56.37 kJ mol−1, from dynamic
NMR data, and 57.68 kJ mol−1, from theoretical calculation. Such a
dynamic NMR behavior was not seen in the 1H NMR spectra of 2 or
4; because, the p-tolyl groups in both later compounds are not in
eclipsed conformations.
˚
the phenyl ring, and H(21C) of the methyl group, is only 2.98 A. On
˚
the other side of phenyl ring, H(14A) is 2.99 A apart from H(21B)
[27].
In solution, the rotation of phenyl ring around C(4)–C(13) bond,
should impose a closer contact and lead to more repulsion between
protons. So, the rotation of phenyl ring is restricted by steric influ-
ence of its vicinal methyl substituent.
Fig. 3 shows the aromatic region of variable temperature 1H
NMR spectra of 3. At temperatures lower than 248 K, the phenyl

1802
K. Marjani et al. / Spectrochimica Acta Part A 79 (2011) 1798–1802
Acknowledgments
[15] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
V.G. Zakrzewski, J.A. Montgomery Jr., R.E. Stratmann, J.C. Burant, S. Dapprich,
J.M. Millam, A.D. Daniels, K.N. Kudin, M.C. Strain, Ö. Farkas, J. Tomasi, V. Barone,
M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski,
G.A. Petersson, P.Y. Ayala, Q. Cui, K. Morokuma, P. Salvador, J.J. Dannenberg,
D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J. Cioslowski, J.V. Ortiz,
A.G. Baboul, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komáromi, R. Gom-
perts, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara,
M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, J.L. Andres, C.
Gonzalez, M. Head-Gordon, E.S. Replogle, J.A. Pople, Gaussian 98, Gaussian, Inc.,
Pittsburgh, PA, 1998.
The financial support from Tarbiat Moalem University is grate-
fully acknowledged.
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