Molecular dynamics of 6-methyl-2-phenyl-2,3-dihydro-4H-chromen-4-one and 6-methyl-2-(4-nitrophenyl)-2,3-dihydro-4H-chromen-4-one (flavanone) derivatives in a solution studied by NMR spectroscopy

Article abstract of DOI:10.1002/mrc.3933

Molecular dynamics of benzoxazepin, oxime, pyrazole, and thiosemicarbazone derivatives of some flavanones have been investigated in a solution using NMR. The results confirm the formation of different O-H?O, O-H?N, N?H-N type intramolecular hydrogen bonds in the pyrazole and oxime molecules. The rotational barrier energy and energy of intramolecular hydrogen bonds have been determined. Copyright

Full text of DOI:10.1002/mrc.3933

Research Article
Received: 9 October 2012
Revised: 9 January 2013
Accepted: 10 January 2013
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/mrc.3933
Molecular dynamics of 6-methyl-2-phenyl-2,
3-dihydro-4H-chromen-4-one and 6-methyl-2-
(4-nitrophenyl)-2,3-dihydro-4H-chromen-4-one
(flavanone) derivatives in a solution studied by
NMR spectroscopy
Ibrahim Garib Mamedov,* Musa Rza Bayramov, Yegana Vagif Mamedova and
Abel Mammadali Maharramov
Molecular dynamics of benzoxazepin, oxime, pyrazole, and thiosemicarbazone derivatives of some flavanones have been
investigated in a solution using NMR. The results confirm the formation of different O–HꢀꢀꢀO, O–HꢀꢀꢀN, NꢀꢀꢀH–N type
intramolecular hydrogen bonds in the pyrazole and oxime molecules. The rotational barrier energy and energy of intramolecular
hydrogen bonds have been determined. Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: flavanone; benzoxazepin; oxime; thiosemicarbazone; molecular dynamics; hydrogen bond; conformers
PL1 = 3 dB; and for 13C: digital resolution = 0.27 Hz, SW= 17 985 Hz,
TD= 64 K, SI = 32K, 90ꢁ pulse length = 9 ms, and PL1 = 1.5 dB.
Introduction
NMR spectroscopy plays an important role in studying various
interactions in solutions including hydrogen bond formations.
The NMR line shape is sensitive to temperature and chemical
exchange processes and can be used successfully for the study
of fast reversible reactions. Thus, NMR has become an important
tool to evaluate the kinetics of reactions at equilibrium over a
very large dynamic range, and its results have theoretical and
practical significance for chemistry, biochemistry, and molecular
physics.[1–16] We have applied these methods to benzoxazepin,
pyrazole, oxime, and thiosemicarbazone derivatives of some
flavanones. The flavanones are naturally occurring heterocyclic
compounds, and these molecules have potential biological and
pharmacological activities.[17–23] Analogues of benzoxazepin
are extremely potent activators of human transient receptors.[24,25]
Oxime compounds are well known as antidotes for nerve agents,
analytical reagents.[26–30] Semicarbazones and thiosemicarbazones
are used in medicine, especially as anticancer chemotherapeutic
agents, in the treatment of tuberculosis, and others.[31–34]
NMR-grade DMSO-d6 (99.7%, containing 0.3% H2O), acetone-d6
(99.7%), and CCl4 (100%, several drops of D2O were added for
the lock signal as external standard) were used for the solutions
of benzoxazepin, oxime, pyrazole, and thiosemicarbazones.
The rate constants for the two-center exchange processes at the
coalescence temperature calculated by the formula kc =2.22dn (dn,
difference of resonance frequency).[2]
The intramolecular hydrogen bond energies have been calculated
with T. Schaefer’s formula.
Δd ¼ ꢂ0:4 ꢃ 0:2 þ E
where Δd is given in parts per million relative to phenol
(4.29 ppm)[35] and E in kilocalorie per mole.
The calculation errors for two exchange sites were ꢃ5% and
for hydrogen bond energies ꢃ0.2 kcal/mol.
Synthesis
The (4Z)-6-methyl-2-phenyl-2,3-dihydro-4H-chromen-4-one oxime
II
mp
(II, T
= 193ꢁC, yield ~89%), 7-methyl-2-phenyl-3,4-dihydro-1,
4-benzoxazepin-5(2H)-one (III, the compound has high viscosity and
Experimental
red color, yield ~69%), 3-(2-hydroxy-5-methylphenyl)-5-phenyl-4,
NMR Spectra
IV
5-dihydro-1H-pyrazole-1-carbothioamide (IV, T = 238–240 ꢁC,
mp
NMR experiments have been performed on a BRUKER FT NMR
yield ~43%), and (4E)-[(4-aminocarbonothioyl)hydrazono]-3,
1
spectrometer AVANCE 300 (300 MHz for H and 75 MHz for 13C)
with a BVT 3200 variable temperature unit in 5-mm sample tubes
using Bruker Standard software (TopSpin 3.1). The 1H and 13C
chemical shifts were referenced to internal TMS; the experimental
parameters for 1H were as follows: digital resolution = 0.23 Hz,
SW = 7530 Hz, TD = 32 K, SI = 16 K, 90ꢁ pulse length = 10 ms, and
*
Correspondence to: Ibrahim Garib Mamedov, Chemical Faculty, NMR Laboratory,
Baku State University, Z. Khalilov 23, Baku, Azerbaijan. E-mail: bsu.nmrlab@mail.ru
Chemical Faculty, NMR Laboratory, Baku State University, Z. Khalilov 23, Baku,
Azerbaijan
Magn. Reson. Chem. (2013)
Copyright © 2013 John Wiley & Sons, Ltd.

I. G. Mamedov et al.
4-dihydro-6-methyl-2-phenyl-2H-1-benzopyran (V, T Vmp = 240–
has been investigated. The preferred twist-boat conformation
for seven-membered ring of 7-methyl-2-phenyl-3,4-dihydro-
1,4-benzoxazepin-5(2H)-one (III) (Fig. 1) was confirmed by
dynamic NMR (DNMR) investigation at the temperature interval
of ꢂ90 to +50 ꢁC in 5% acetone-d6 solution, NOESY experiment,
and literature data.[39,40] DNMR spectra do not show any
changes in the signals from the investigated compound. That
means the time average conformation is present in the solution.
242 ꢁC, yield ~78%) have been prepared by the known literature
methods[36–38] (II–V are known compounds in the literature)
(Scheme 1).
The new compounds (Z)-3-hydroxy-1-(2-hydroxy-5-methylphenyl)-
3-(4-nitrophenyl)propan-1-one oxime (VII) and (E)-3-hydroxy-
1-(2-hydroxy-5-methylphenyl)-3-(4-nitrophenyl)propan-1-one oxime
(VIII) were obtained by the reaction of 0.1 mol 6-methyl-2-(4-nitrophe-
nyl-2,3-dihydro-4H-chromen-4-one (VI) with 0.2 mol hydroxylamine
hydrochloride (NH2OHꢀHCl) in 130 ml ethanol at temperature 78 ꢁC,
1
The H NMR spectrum at ꢂ50 to ꢂ90 ꢁC showed that
hygroscopic H2O from compound (III) in acetone-d6 gave two
signals instead of one at 3.20 and 3.32 ppm. These results can be
explained by the formation of stable intermolecular hydrogen
bond (in the low exchange at ꢂ50 to ꢂ90 ꢁC) between the
compound (III) and hygroscopic water.
In continuation of the researches, we have investigated the
product of the reaction between 6-methyl-2-phenyl-2,3-dihydro-
4H-chromen-4-one (I) and thiosemicarbazide at the presence of
sodium ethoxide in ethanol. The 1D and 2D NMR investigations
confirmed the opening of the six-membered pyrone ring in
the 6-methyl-2-phenyl-2,3-dihydro-4H-chromen-4-one (I) and the
reformation of the new five-membered pyrazole ring in the (IV).
In earlier studies, research groups showed the presence of two
conformers for the molecule thiosemicarbazones (Scheme 2) as
the result of the rotation around the N2–C3 bond and theoretically
calculated the existence of a partial double bond between
N2 and C3.[12,41]
reaction time 3 h[36] (T = 162 ꢁC and T = 178 ꢁC, yield ~85%)
VII
mp
VIII
mp
(Scheme 1).
The purity and structure of the synthesized compounds are
confirmed by layer chromatography (Silufol UV-254, 0.1-mm
silica gel plates, using iodine vapor as visualizing agent, eluent
hexane/ethyl acetate, 7:2), 1H NMR, 13C NMR, DEPT, COSY, NOESY,
HMBC, and HMQC. The 1H and 13C NMR data of compounds (II–V,
VII, and VIII) are given in Table 1.
Results and Discussion
In the present work, we have decided an investigation of the
molecular dynamics of benzoxazepine, oxime, thiosemicarbazone,
and pyrazole derivatives of some flavanones (I and VI) in a solution
using NMR spectroscopy.
Initially, we have investigated the (4Z)-6-methyl-2-phenyl-2,3-
dihydro-4H-chromen-4-one oxime (II). Detailed NMR investigations
confirmed that pyrone ring in the 6-methyl-2-phenyl-2,3-dihy-
dro-4H-chromen-4-one (I) has not opened and only (Z)-oxime
(II) has been obtained.
Subsequently, the 7-methyl-2-phenyl-3,4-dihydro-1,4-benzoxaze-
pin-5(2H)-one (III) being the product of the Beckman rearrangement
of (4Z)-6-methyl-2-phenyl-2,3-dihydro-4H-chromen-4-one oxime (II)
For the molecule 3-(2-hydroxy-5-methylphenyl)-5-phenyl-4,
5-dihydro-1H-pyrazole-1-carbothioamide (IV), DNMR investigations
have been carried out in 5% DMSO-d6 and 0.5–5% CCl4 solutions
by 1H and 13C NMR spectroscopy at the temperature interval
of 20–90 ꢁC. In the 13C spectrum of 5% DMSO-d6 solution, we
observed one signal for all carbons (from the compound IV)
as a result of fast exchange between the conformers at the
20–90 ꢁC.
Scheme 1. Synthesis of the oximes (II, VII, and VIII), benzoxazepin (III), pyrazole (IV), and thiosemicarbazone (V) derivatives of flavanones (I and VI).
wileyonlinelibrary.com/journal/mrc
Copyright © 2013 John Wiley & Sons, Ltd.
Magn. Reson. Chem. (2013)

Molecular dynamics of some flavanones and its derivatives in a solution studied by NMR
Magn. Reson. Chem. (2013)
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

I. G. Mamedov et al.
Scheme 3. Two conformers of the molecule 3-(2-hydroxy-5-methylphenyl)-
5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (IV).
Figure 1. Twist-boat conformation for seven-membered ring of
7-methyl-2-phenyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-one (III).
Our studies confirmed the formation of two intramolecular
hydrogen bonds (O–HꢀꢀꢀN and NꢀꢀꢀH–N type) for the one conformer
and O–HꢀꢀꢀN type for the other one (intermolecular hydrogen
bond strongly depends on concentration and temperature).
The energy of O–HꢀꢀꢀN-type intramolecular hydrogen bonds at
20 ꢁC in the 0.5% CCl4 solution is equal to 5.41 ꢃ 0.2 kcal/mol
(or 22.7 kJ/mol). Intramolecular hydrogen bond energies for
the molecule (IV) have been calculated with Schaefer’s
formula.[35]
Scheme 2. The presence of two conformers for the molecule thiosemi-
carbazones resulting from rotation around the N2–C3 bond.
The rotational barrier around the N2–C3 bond for the molecule (IV)
has been calculated from the 1H NMR spectra in 5% DMSO-d6. The
NMR spectrum of the two exchange sites have been calculated
by formula kc = 2.22dn resulting in the rate constants (kc = 57.48 sꢂ1
at Tc = 297K) in DMSO-d6 solution. The free energy of activation has
been calculated by the formula[2]
But in the 1H NMR spectrum of 5% DMSO-d6 solution at 20 ꢁC,
two singlet signals appear instead of one for the –NH2 protons
resulting from rotations around the N2–C3 bond (Scheme 3).
Concentrations and temperature changes have only a weak
influence on the OH and NH2 chemical shifts at 9.53 and
8.07 ppm (Table 2).
ΔGc ¼ 2:3RTc½10:32 þ logðTc=kcÞꢄ ꢅ 14:95 kcal=mol
Table 2. Chemical shifts of OH (dOH) and NH2 (dNH) protons of IV and VIII, in different solvents at various concentrations and temperatures
IV
VIII
Solvent
Concentration,
%
Temperature,
ꢁC
dOH and dNH2, ppm
Solvent
Concentration,
%
Temperature, dOH and dN–OH, ppm
ꢁC
DMSO-d6
5
5
20
24
40
60
90
20
20
20
9.53 (OH) and 8.07
(NH2)
DMSO-d6
5
20
11.10 (N–OH) and
11.50 (OH)
9.51 (OH) and 7.96
(NH2)
5
9.49 (OH) and 7.85
(NH2)
5
9.43 (OH) and 7.82
(NH2)
5
9.35 (OH) and 7.62
(NH2)
CCl4
5
9.50 (OH) and 7.98
(NH2)
DMSO-d6
1
20
10.99 (N–OH) and
11.49 (OH)
3
9.40 (OH) and 7.95
(NH2)
0.5
9.30 (OH) and 7.87
(NH2)
CCl4
5
1
20
20
20
20
20
10.43 (N–OH) and
10.92 (OH)
10.40 (N–OH) and
10.88 (OH)
0.5
5
10.40 (N–OH) and
10.87 (OH)
Acetone-d6
Acetone-d6
10.80 (N–OH) and
11.10 (OH)
1
10.57 (N–OH) and
11.00 (OH)
wileyonlinelibrary.com/journal/mrc
Copyright © 2013 John Wiley & Sons, Ltd.
Magn. Reson. Chem. (2013)

Molecular dynamics of some flavanones and its derivatives in a solution studied by NMR
Subsequently, we have investigated the (4E)-[(4-aminocarbo-
nothioyl)hydrazono]-3,4-dihydro-6-methyl-2-phenyl-2H-1-benzopyran
(V) (or 6-methyl-2-phenyl-2,3-dihydro-4H-chromen-4-one thio-
semicarbazone). Detailed NMR investigations confirmed that pyr-
one ring in the 6-methyl-2-phenyl-2,3-dihydro-4H-chromen-4-one
(I) has not opened and the compound (V) has been obtained.
For the molecule (V), DNMR investigations have been carried
nitrophenyl)-2,3-dihydro-4H-chromen-4-one (VI) and hydroxyl-
amine hydrochloride in ethanol. Our studies confirmed that
comparing the (I), in the 6-methyl-2-(4-nitrophenyl)-2,3-
dihydro-4H-chromen-4-one (VI) opening the pyrone ring and
formation of 8.9% (Z)-3-hydroxy-1-(2-hydroxy-5-methylphenyl)-3-
(4-nitrophenyl)propan-1-one oxime (VII) and 61.1% (E)-3-hydroxy-1-
(2-hydroxy-5-methylphenyl)-3-(4-nitrophenyl)propan-1-one oxime (VIII).
The isomers have been separated by CCl4 (E-isomer by cold CCl4
solution).
1
out in 5% DMSO-d6 solution by H and 13C NMR spectroscopy
in the temperature interval of 22–70 ꢁC. In the 13C spectrum of
5% DMSO-d6 solution, we observed one signal for all carbons
as a result of fast exchange between the conformers at the
In the 1H NMR spectra for the molecule (VII) obtained in CCl4
solutions, a doublet for the CH2 group at 3.45 ppm and a triplet
1
1
20–70 ꢁC. But in the H NMR spectrum at 22 ꢁC, two singlet
for the CH group at 5.55 ppm have been observed (also in H
signals (at 8.05 and 8.33 ppm) are observed instead of a singlet
for the –NH2 protons (the singlet signal at 8.1 ppm belongs to
aromatic CH, which probably presents interaction between
CH N). Our NMR investigations confirm the possible existence
of two conformers in 5% DMSO-d6 solution in the temperature
interval of 22–70 ꢁC for the molecule 6-methyl-2-phenyl-2,3-dihy-
dro-4H-chromen-4-one thiosemicarbazone (V) (N2ꢂC3 rotational
conformers; Scheme 4). Obtained data explain the temperature
dependence of the 1H NMR spectra (the free energy of activation
is equal to 16.25 kcal/mol, then kc = 139.19 sꢂ1 at Tc = 333 K).
In continuation of our investigations, we have researched the
new products of the reaction being between 6-methyl-2-(4-
NMR spectra in DMSO-d6 and acetone-d6, the same multiplicity
between CH and CH2 groups have been observed).
In the 1H NMR spectra for the molecule (VIII) obtained in
acetone-d6 solution at 22 ꢁC, we have observed a doublet for
the CH2 group at 3.35 ppm and a triplet for the CH group at
5.41 ppm. The 13C NMR spectrum in acetone-d6 solution at
ꢂ90 ꢁC (Fig. 2) has showed two signals instead of one for some
1
carbons. But in the H NMR spectra obtained in DMSO-d6 and
CCl4 solutions at 22 ꢁC, a doublet of doublets for the CH2 and a
multiplet for the CH groups at 3.2 (or 3.21) and 5.1 (or 5.28) ppm
have been observed. Concentration changes for CCl4 solutions
have only a weak influence on the oxime and phenol OH chemical
shifts at 10.4 and 10.9 ppm (Table 2). Our studies confirmed the
formation of two intramolecular hydrogen bonds (O–HꢀꢀꢀN and
OHꢀꢀꢀO type) for the molecule (VIII) in CCl4 and DMSO-d6. The energy
of O–HꢀꢀꢀNtype intramolecular hydrogen bonds at 22 ꢁC in the 0.5%
CCl4 solution is equal to 7.1ꢃ 0.2 kcal/mol (or 29.7 kJ/mol).
The splitting of the proton and carbon signals at ꢂ90ꢁC, a
doublet from the CH2 and a triplet from the CH groups in
acetone-d6 solution at 22ꢁC show possible existence of conformers
(a, b) due to the predomination rotation around the CH2-CH
bond, a doublet of doublet from the CH2 and a multiplet from
Scheme 4. Two conformers of the molecule 6-methyl-2-phenyl-2,3-
dihydro-4H-chromen-4-one thiosemicarbazone (V).
Figure 2. 13C NMR spectral sections of VIII in acetone-d6 at the temperature interval ꢂ90 and +22 ꢁC.
Magn. Reson. Chem. (2013)
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

I. G. Mamedov et al.
[5] A. A. Vashman, I. S. Pronin, Nuclear Magnetic Relaxation Spectros-
copy, Nauka, Moscow, 1986.
[6] A. A. Vashman, I. S. Pronin, Nuclear Magnetic Relaxation and its
Application in Chemical Physics, Nauka, Moscow, 1979.
[7] N. D. Sokolov, Hydrogen Bond, Nauka, Moscow, 1981.
[8] T. Yamaguchi, N. Matubayasi, M. Nakahara. J. Mol. Liq. 2005, 119, 119.
[9] A. Szady-Chelmieniecka, E. Grech, Z. Rozwadowski, T. Dziembowska,
W. Schilf, B. Kamienski. J. Mol. Struct. 2001, 565–566, 125.
[10] A. J. Horsewill, A. Aibout. J. Phys. Condens Matter 1989, 1, 9609.
[11] R. A. Bernheim, H. S. Gutowsky, I. J. Lawrenson. J. Chem. Phys. 1961,
34, 565.
[12] I. G. Mamedov, U. Eichhoff, A. M. Maharramov, M. R. Bayramov,
Y. V. Mamedova. Cent. Eur. J. Chem. 2012, 10, 241.
[13] I. G. Mamedov, U. Eichhoff, A. M. Maharramov, M. R. Bayramov, Y. V.
Mamedova. Magn. Reson. Chem. 2010, 48, 671.
[14] I. G. Mamedov, U. Eichhoff, A. M. Maharramov, M. R. Bayramov,
Y. V. Mamedova. Appl. Magn. Reson. 2010, 3, 257.
[15] I. G. Mamedov, A. M. Maharramov, M. R. Bayramov, Y. V. Mamedova.
Russ. J. Phys. Chem. 2010, 12, 2182.
[16] A. M. Maharramov, M. R. Bayramov, I. G. Mamedov. Russ. J. Phys.
Chem. 2008, 7, 1382.
[17] M. Liu, P. Wilairat, M. Go. J. Med. Chem. 2001, 44, 4443.
[18] V. J. Ram, A. S. Saxena, S. Srivastava, S. Chandra. Bioorg. Med. Chem.
Lett. 2000, 10, 2159.
[19] J. N. Dominguez, J. E. Charris, G. Lobo, N. G. Dominguez, M. M. Moreno,
F. Riggione, E. Sanchez, J. Olson, P. J. Rosenthal. Eur. J. Med. Chem.
2001, 36, 555.
Scheme 5. Conformers of the molecule (E)-3-hydroxy-1-(2-hydroxy-5-
methylphenyl)-3-(4-nitrophenyl)propan-1-one oxime (VIII) in acetone-d6,
DMSO-d6, and CCl4 solutions.
the CH groups in DMSO-d6, CCl4 solution show possible exis-
tence of conformer (c) as a result of the formation of two
intramolecular hydrogen bonds and complication of rotation
around the CH2–CH bond (Scheme 5).
Conclusions
[20] J. N. Dominguez, C. Leon, J. R. Rodrigues, N. G. Dominguez, J. Gut,
P. J. Rosenthal. J. Med. Chem. 2005, 48, 3654.
Our detailed NMR investigations confirmed the formation of
only (Z)-oxime for the compound (II). The preferred twist-boat
conformation for seven-membered ring of the molecule (III) is
confirmed by the DNMR investigation at different temperature, NOESY
experiment, and literature data. The 1D and 2D NMR experiments
showed the opening of the six-membered pyrone ring in the
(I) and the formation of the new five-membered pyrazole ring in
the (IV). Detailed NMR explorations confirmed the presence of
two conformers for the molecules (IV) and (V) as a result of the
rotation around the N2–C3 bond.
Our studies showed that comparison of (II) and (VI), where in con-
tradistinction to (II) in the (VI) the pyrone ring have opened and 38.9%
(Z)- (VII) and 61.1% (E)-oxime (VIII) have obtained. The results can be
explained by the existence of conformers (as a result of the rotation
around the CH2–CH bond) for the molecule (E)-3-hydroxy-1-(2-
hydroxy-5-methylphenyl)-3-(4-nitrophenyl)propan-1-one oxime (VIII).
For the molecules (IV) and (VIII), the O–HꢀꢀꢀN- and O–HꢀꢀꢀO type
intramolecular hydrogen bond energies and, for the (IV) and (V),
rotational barrier energies (ꢅ14.95 and 16.25 kcal/mol) have been
calculated.
[21] L. Shi, X. E. Feng, J. R. Cui, L. H. Fang, G. H. Du, Q. S. Li. J. Med. Chem.
2010, 18, 5466.
[22] T. J. Ha, M. S. Yang, D. S. Jang, S. U. Choi, K. H. Park. Bull. Korean Chem.
Soc. 2001, 22, 97.
[23] M. Cabera, M. Simoens, G. Falchi, M. L. Lavaggi, O. E. Piro, E. E.
Castellano, A. Vidal, A. Azqueta, A. Monge, A. L. Cerain, G. Sagrera,
G. Seoane, H. Carecetto, M. Gonzalez. J. Bioorg. Med. Chem. 2007,
10, 3356.
[24] H. J. M. Gijsen, D. Berthelot, M. Zaja, B. Brone, I. Geuens, M. Mercken.
J. Med. Chem. 2010, 53, 7011.
[25] E. J. Olajos, H. H. Salem. J. Appl. Toxicol. 2001, 21, 355.
[26] R. E. Plapinger, O. O. Owens. J. Org. Chem. 1956, 21, 1186.
[27] A. N. Petrov, G. A. Sofronov, S. P. Nechiporenko, I. N. Somin. Russ.
Chem. J. 2004, 2, 110.
[28] G. Y. Yang, J. H. Yoon, C. M. Seong, N. S. Park, Y. S. Jung. Bull. Korean
Chem. Soc. 2003, 24, 1368.
[29] M. Stojilkovic, M. Jokanovic. Arh. Hig. Rada Toksikol. 2006, 57, 435.
[30] V. M. Peshkova, V. M. Savostina, Y. K. Ivanova, Oximes, Nauka,
Moscow, 1977.
[31] G. Domagk. An. Rev. Tubreit 1950, 16, 8.
[32] W. L. Nobles. J. Am. Chem. Soc. 1955, 77, 6675.
[33] H. H. Fox. J. Org. Chem. 1952, 17, 555.
[34] Z. G. Jiang, M. S. Lebowitz, H. A. Ghanbari. CNS Drug Rev. 2006,
12, 77.
[35] T. Schaefer. J. Phys. Chem. 1975, 79, 1888.
[36] L. F. Tietze, T. Eicher, Reaktionen und Synthesen im Organisch-
Chemischen Praktikum und Forschungslaboratorium, Stuttgart,
New York, Georg Thieme Verlag, 1991.
[37] A. Khodairy. J. Chine Chem. Society 2007, 54, 93.
[38] L. Fieser, Organic Experiments, D.C. Heath and Company, USA, 1992.
[39] A. Entrena, J. Campos, J. A. Gómez, M. A. Gallo, A. Espinosa. J. Org.
Chem. 1997, 62, 337.
References
[1] V. I. Bakhmutov, Practical NMR Relaxation for Chemists, Wiley,
England, 2004.
[2] H. Günther, NMR Spectroscopy – an Introduction, Wiley, New York, 1980.
[3] L. M. Jackman, F. A. Cotton, Dynamic Nuclear Magnetic Resonance
spectroscopy, Academic Press, New York, 1975.
[4] J. Sandstrom, Dynamic NMR Spectroscopy, Academic Press,
New York, 1982.
[40] V. M. Potapov, Stereochemistry, Khimiya, Moscow, 1988.
[41] N. D. Silva, T. V. Albu. Cent. Eur. J. Chem. 2007, 5, 396.
wileyonlinelibrary.com/journal/mrc
Copyright © 2013 John Wiley & Sons, Ltd.
Magn. Reson. Chem. (2013)