Z/E(C=C)-isomerization of coumarin enamines induced by organic solvents

Article abstract of DOI:10.1016/j.mencom.2009.07.014

Imines of 3-formyl-4-hydroxycoumarin have been found to exist in E- and Z-ketoenamine forms in a crystal state and undergo Z/E-isomerization around the C=C bond in organic solvents (e.g., CHCl₃).

Full text of DOI:10.1016/j.mencom.2009.07.014

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Mendeleev
Communications
Mendeleev Commun., 2009, 19, 214–216
Z/E(C=C)-isomerization of coumarin enamines
induced by organic solvents
Valery F. Traven,*a Ivan V. Ivanov,a Victor S. Lebedev,a Boris G. Milevskii,a
Tat’yana A. Chibisova,a Natalya P. Solov’eva,b Vladimir I. Polshakov,b
Olga N. Kazheva,c Grigorii G. Alexandrovd and Oleg A. Dyachenkoc
a D. I. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russian Federation.
Fax: +7 495 609 2964; e-mail: traven@muctr.ru
b Center for Drug Chemistry, 119815 Moscow, Russian Federation
c Institute of Problems of Chemical Physics, Russian Academy of Sciences, 142432 Chernogolovka,
Moscow Region, Russian Federation
d N. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 119991 Moscow,
Russian Federation
DOI: 10.1016/j.mencom.2009.07.014
Imines of 3-formyl-4-hydroxycoumarin have been found to exist in E- and Z-ketoenamine forms in a crystal state and undergo
Z/E-isomerization around the C=C bond in organic solvents (e.g., CHCl3).
Noncovalent interactions play an important role in organic
H
X
H
H
X
chemistry, in the formation and function of supramolecular
structures and various biological substrates.1–3 Moreover, solvato-
chromic compounds sensitive to the noncovalent interactions
are of interest for the creation of novel sensor and signaling
systems.4,5 Heteroaromatic imines are well known for their
ability to undergo solvent driven isomerizations.6–9 The solvato-
chromic behaviour of coumarin derivatives is of special interest
due to their prominent fluorescence potential.10 Earlier, we
have found some imines of 8-formyl-7-hydroxycoumarin to
undergo E/Z-isomerization around the C=N bond followed by
fluorescence modulation.11
O
N
O
N
H
O
O
O
O
I, E-hydroxyimine
II, Z-hydroxyimine
H
X
H
O
N
O
O
H
O
X
N
H
O
O
Here, we report the Z/E-isomerization of imines 1 and 2
of 3-formyl-4-hydroxycoumarin induced by organic solvents.
Spectral grade CDCl3 and [2H6]DMSO have been used. The
structure of imine 1 has been studied by Wolfbeis et al.,12
however, its E/Z-isomerization has not been reported.
III, E-ketoenamine
IV, Z-ketoenamine
Scheme 1 Tautomeric forms of 3-formyl-4-hydroxycoumarin imines.
NH) protons, which form intramolecular hydrogen bonds and
can be seen in the region of 12–14 ppm for all four isomers. We
have found both exchangeable and 9-H signals to appear in
1H NMR spectra as pairs of doublets (see Online Supple-
mentary Materials). Splitting of these signals is due to scalar
interaction between NH and 9-H protons. This indicates on
the existence of imines 1 and 2 in solution in the E- and
Z-ketoenamine forms. The ratio of signal intensities is equal for
both NH and 9-H doublets and corresponds to the relative
contents of E- and Z-isomers in solution. Coupling constants in
both (E- and Z-) isomers are about 13–15 Hz, which correspond
14
15
OH
4
13
9
5
8
10
4a
8a
12
3
6
7
N
11
10a
2
OH
O
O
9
11
14
5
8
4
4a
8a
10
3
6
7
12
13
1
N
10a
2
15
O
O
2
†
3-(p-Tolylaminomethylene)chroman-2,4-dione 1. Yellow needle-like
crystals (from ethanol), mp 192–194 °C (lit.,12 mp 191 °C). 1H NMR
(200 MHz, CDCl3) d: 13.60 (d, 0.66H, NH, J10,9 13.7 Hz), 11.91 (d,
0.34H, NH, J10,9 14.5 Hz), 9.98 (d, 0.34H, 9-H, J9,10 14.5 Hz), 9.87
(d, 0.66H, 9-H, J9,10 13.7 Hz), 8.04 (dd, 1H, 5-H, J5,6 7.7 Hz, J5,7 1.7 Hz),
7.66–7.70 (m, 1H, 7-H), 7.53–7.58 (m, 2H, 6-H, 8-H), 7.20–7.40 (m,
4H, 1'-H, 2'-H, 4'-H, 5'-H), 2.39 (s, 3H, Me).
3-(Benzylaminomethylene)chroman-2,4-dione 2. Yellow crystals (from
toluene), mp 165–167 °C (lit.,13 167–168 °C). 1H NMR (200 MHz, CDCl3)
d: 12.30 (m, 0.7H, NH), 10.50 (m, 0.3H, NH), 8.66 (d, 0.3H, 9-H,
J9,10 14.9 Hz), 8.49 (d, 0.7H, 9-H, J9,10 13.8 Hz), 8.07 (dd, 0.3H, 5-H,
J5,6 7.7 Hz, J5,7 1.07 Hz), 8.08 (dd, 0.9H, 5-H, J5,6 7.7 Hz, J5,7 1.5 Hz),
7.55–7.66 (m, 1H, 7-H), 7.42–7.53 (m, 2H, 6-H, 8-H), 7.20–7.40 (m,
5H, 1'-H, 2'-H, 3'-H, 4'-H, 5'-H).
Due to a solvent impact on the hydrogen bonding in com-
pounds 1 and 2, one can expect solvent driven tautomeric trans-
formations and E/Z-isomerizations, including rotation around
both C=N and C=C bonds (Scheme 1).
Imines 1 and 2 have been synthesized by straightforward pro-
cedure from 3-formyl-4-hydroxycoumarin and related amines –
p-toluidine and benzylamine, respectively. Their structures have
been confirmed by 1H and 13C NMR spectroscopy and comparison
of their melting points with published data.12,13,†
The most characteristic signals of imines 1 and 2 in 1H NMR
spectra (both in CDCl3 and in [2H6]DMSO) belong to protons
9-H located at 8.5–9.5 ppm and to the exchangeable (OH or
– 214 –
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Mendeleev Commun., 2009, 19, 214–216
in Figure 1.‡ One can see that molecules A and B are E- and
Z-ketoenamine isomers respectively. Selected bond distances
and angles of imine 2 are given in Online Supplementary
Materials.
Table 1 Results of GIAO chemical shift calculations for representative
nuclei in E- and Z-ketoenamine forms of 1. Shown are isotropic values
calculated using TMS as standard. Experimentally measured values are
shown in parentheses.
As one could expect, 1H NMR spectra of the imines are
sensitive to the solvent and also change with time upon the
dissolution of the substances. Thus, in spectrum recorded for
freshly prepared solution in CDCl3 intensity of lower field doublet
of 9-H proton (9.00 ppm, J9,10a 14.4 Hz: Z-isomer) of imine 1 is
much higher than analogous higher field signal (8.90 ppm,
J9,10a 13.9 Hz: E-isomer). Measurement of the spectrum of the
same solution after 25 h at room temperature shows a decrease
of intensity of the signal at 9.00 ppm from 90 to 30% and
corresponding increase of the intensity of the doublet at 8.90 ppm
from 10 to 70%. Predominance of the Z-isomer in freshly
prepared solution seems to be explained by its preference in the
crystal state.
The equilibrium also depends on temperature. Thus, at 40 °C
equilibrated content of E-isomer decreases to 65% and amount
of Z-isomer proportionally increases to 35%. Cooling of this
solution to room temperature during several hours restores the
previous E/Z ratio (70 and 30%). Monitoring of the intensities
of the signals of E- and Z-isomers of imine 1 with time at several
temperatures between 30 and 50 °C allows us to calculate E/Z
isomerisation rate constants at these temperature points. Decay
of the signals of Z-isomer and growth of the signals of E-isomer
on the initial stage of the reaction (~10% of turnover) turned to
be well described by the first-order kinetics. Using this assump-
tion, activation energy of 84 6 kJ mol–1 for isomerization of
imine 1 Z-ketoenamine form to correspondent E-isomer was
calculated from the linear fitting of the ln k to the values of 1/T
(Figure 2, inset).
Isotropic chemical shift/ppm
Hydrogen and
carbon nuclei
E-isomer
Z-isomer
NH
9-H
12.60 (13.60)
9.07 (8.90)
11.40 (12.00)
9.46 (9.00)
C(2)
C(3)
C(4)
C(9)
C(10)
167.80 (163.60)
105.10 (98.37)
188.30 (181.60)
161.62 (154.60)
124.32 (137.62)
169.30 (165.20)
107.10 (98.39)
184.30 (178.50)
160.67 (153.20)
124.24 (134.48)
to the trans-orientation of C(9)–H and N–H bonds. As one can
see from the structures of two ketoenamine isomers, this
orientation of C(9)–H and N–H bonds is stabilized by
intramolecular H-bonds formed between NH proton and
carbonyl oxygen in either the 4-position (in E-isomer) or the 2-
position (in Z-isomer).
The 13C NMR spectra of both imines confirm their existence
as two E- and Z-ketoenamine isomers. Signals of atom C(4) of
predominant isomers (at 181.6 and 181.2 ppm, respectively, for
imines 1 and 2) are shifted to lower field comparing to that
of the minor isomers (at 178.5 and 178.4 ppm, respectively),
whereas the signal of atom C(2) has opposite shielding effect.
This can easily be explained by existence of two hydrogen
bonds, C(4)=O···H–N and C(2)=O···H–N in E- and Z-keto-
enamines, respectively. Signals of atom C(2) of predominant
isomers (at 163.6 and 163.7 ppm, respectively) are shifted to
higher field comparing to that of the minor isomers (at 165.2 and
164.9 ppm, respectively). Both C(2) signals appear as doublets
due to the spin–spin interaction of atom C(2) with proton 9-H.
Heteroconstants of minor isomers turned to be definitely larger
(JC(2),9-H 9.94 and 10.9 Hz, respectively, for imines 1 and 2)
than that of major isomers (JC(2),9-H 3.07 Hz for both imines).
The above values of JC(2),9-H show the minor isomers to be
Z-ketoenamines, since these isomers possess transoid orientation
of C(2)–C(3) and C(9)–H bonds. As a result major isomers
should be considered as E-isomers.
The activation energy of the C(3)–C(9) bond rotation in
compound 1 was also estimated using the quantum mechanical
calculations by the Hartree–Fock method in 6-31++G(d,p) basis
set. Theoretical value of 130 kJ mol–1 is notably larger than
experimentally measured one. The most probable explanation
could be related to the solvent effects. Indeed, calculations were
carried out in vacuo, whereas experimentally measured value
There are no signals of E- and Z-hydroxyimine tautomers
C(5A)
O(3A)
A
1
both in the H NMR and in the 13C NMR spectra. These data
C(6A)
C(16A)
C(3A)
agree with results of AM1 calculations: energies of formation
of E- and Z-hydroxyimine tautomers are 6–6.5 kcal mol–1
higher than those of E- and Z-ketoenamines.
C(15A)
C(14A)
C(7A)
C(8A)
C(2A)
C(1A)
O(2A)
O(1A)
The energies of formation of E- and Z-ketoenamines, III and
IV, charge distribution and lengths of intramolecular hydrogen
bonds in both isomers have been calculated using the B3LYP DFT
method implied in Gaussian 98 and basis set 6-311++G(d,p).14–17
Results of the calculations show that E-ketoenamine has lower
energy of formation than Z-isomer and, therefore, is more stable
(ΔE = 0.65 kcal mol–1). Such an energy difference corresponds
to the thermodynamic equilibrium between two states with
populations of ~75 and ~25%, respectively, which are close to
the experimentally measured values (~70 and 30%). B3LYP DFT
calculations with gauge-including atomic orbitals (GIAO) method
have been used to estimate isotropic chemical shifts of hydrogen
and carbon nuclei in both isomers of 1. Calculated values show
good qualitative agreement with the experimental values (Table 1).
Results of GIAO calculations also helped to confirm assignments
of signals 9-H in E- and Z-isomers: 9-H in E-ketoenamine has
higher field shift (8.9 ppm) comparing to Z-isomer (9.00 ppm).
X-ray studies confirm the ability of 3-formyl-4-hydroxy-
coumarin imines to exist in two ketoenamine forms. We have
found the crystal packing of 2 to be formed by two isomer
molecules (A and B), located in the same position of crystallo-
graphic cell. Individual structures of these molecules are shown
O(3B)
C(5B)
B
C(6B)
C(3B)
C(16B)
C(2B)
C(7B)
C(8B)
C(15B)
C(14B)
C(1B)
O(1B)
H(1B)
O(2B)
Figure 1 The molecular structure of E- and Z-ketoenamine isomers of
imine 2.
‡
X-Ray diffraction data. At 25–°C crystals of 2 (C17H13NO3, M = 279.28)
are triclinic, space group P1, a = 10.669(2), b = 11.983(2) and c =
= 12.169(2) Å, a = 62.38(3)°, b = 89.29(3)°, g = 81.67(3)°, V = 1361.3(5) Å3,
Z = 4, dcalc = 1.36 g cm–3, m = 0.094 mm–1, reflections observed/independent
9513/5301, 379 parameters refined, R = 0.075 for 2608 reflections with
F0 > 4s(F0). Reflections were collected on a Bruker SMART APEX2 CCD
diffractometer using MoKα radiation. Crystal structure was solved by
direct methods followed with Fourier synthesis using SHELXS-97. All
non-hydrogen atoms were refined using anisotropic full-matrix approxi-
mation using SHELXL-97. Coordinates of hydrogen atoms were calculated.
CCDC 700853 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2009.
– 215 –

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Mendeleev Commun., 2009, 19, 214–216
of E- and Z-isomers.19 Berthet and coworkers have reported
coexistence of spirooxazine and its four transoid photomero-
cyanines.20 The trans-trans-cis/trans-trans-trans isomerization
of photochromic spiropyran merocyanines has been also studied
both experimentally19 and using DFT calculations14 to explain
the solvatochromic effects and sensing properties of organic
substrates.
t/s
0
500 1000 1500 2000 2500 3000 3500 4000 4500
–4.6
–4.7
–4.8
–4.9
–5.0
–5.1
–5.2
–5.3
–5.4
298 K
303 K
308 K
This work was supported by the Russian Foundation for
Basic Research (grant no. 08-03-90016-Bel_a). We acknowledge
the computing resources of Molecular Structure Division of the
National Institute for Medical Research, Mill Hill London.
1/T
313 K
0.00315 0.00325 0.00335
–4.0
–4.5
–5.0
–5.5
–6.0
–6.5
ln k = –9566.4/T + 25.985
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2009.07.014.
Figure 2 Monitoring of the intensities of the signal of imine 1 Z-isomer
with time at different temperatures.
corresponds to the chloroform solution. Difference between
calculated and experimental values (46 kJ mol–1) is in fact close
to the difference between activation energy calculated both
in vacuo and in CH2Cl2 solution (55 kJ mol–1) for E/Z-isomeri-
zation of spiropyran merocyanine carried out using similar DFT
approach.18
References
1
R. J. Williams, M. Dovichi, G. Patony and L. Strekowski, Anal. Chem.,
1993, 65, 601.
2
3
4
G. Patony, J. Salon, J. Sowell and L. Strekowski, Molecules, 2004, 9, 40.
K. Uekama, F. Hirayama and T. Irie, Chem. Rev., 1998, 98, 2045.
C. M. Rudzinski and D. G. Nocera, in Optical Sensors and Switches,
ed. K. S. Schaze, Marcel Dekker, New York, 2001, pp. 1–93.
S. M. Yarmoluk, S. S. Lukashov, M. Yu. Losytskyy, B. Akerman and
O. S. Kornyushyna, Spectrochim. Acta, Part A, 2002, 58, 3223.
W. G. Herkstroeter, J. Am. Chem. Soc., 1976, 98, 330.
V. A. Chernoivanov, A. D. Dubonosov, V. I. Minkin, V. A. Bren’ and
A. E. Lyubarskaya, Zh. Org. Khim., 1989, 25, 443 (in Russian).
A. D. Garnovskii and I. S. Vasil’chenko, Usp. Khim., 2002, 71, 1064
(Russ. Chem. Rev., 2002, 71, 943).
We have found that the solvent effect on Z/E-isomerization
becomes greater when a more polar solvent is used. Thus, the
1H NMR spectrum of imine 1 reflects evidences of its much
faster isomerization in [2H6]DMSO solution. Signal of 9-H at
8.70 ppm is a broad singlet immediately after dissolution of
imine 1 in [2H6]DMSO. This broad signal disintegrates into
two doublets at 8.66 ppm (E-isomer, J9,10a 13.5 Hz, 73%,) and
at 8.72 ppm (Z-isomer, J9,10a 14.8 Hz, 27%) after 4 h. One can
observe similar changes with doublet in lower field (11–14 ppm)
arisen from resonance of NH protons. Two broad NH signals at
13.4 ppm and at 11.7 ppm are seen in 1H NMR spectrum imme-
diately after the dissolving of imine 1 in [2H6]DMSO. The
intensities of signals at 13.5 ppm (E-isomer) and 11.8 ppm
(Z-isomer) have the same ratio as two signals of 9-H proton seen
5
6
7
8
9
E. N. Shepelenko, V. A. Bren’, A. D. Dubonosov, A. E. Lyubarskaya
and V. I. Minkin, Khim. Geterotsikl. Soedin., 1989, 591 [Chem. Heterocycl.
Compd. (Engl. Transl.), 1989, 25, 489].
10 R. P. Haugland, Handbook of Fluorescent Probes and Research Chemicals,
6th edn., Molecular Probes Inc., Eugene, 1996.
11 V. F. Traven, V. S. Miroshnikov, A. S. Pavlov, I. V. Ivanov, A. V. Panov
and T. A. Chibisova, Mendeleev Commun., 2007, 17, 88.
12 P. Ollinger, O. Wolfbeis and H. Junek, Monatsh. Chem., 1975, 106,
963.
13 M. Hamdi, P. Granier, R. Sakellariou and V. Speziale, J. Heterocycl.
Chem., 1993, 30, 1155.
1
in the spectrum after 4 h. No additional changes in H NMR
spectra of imine 1 can be detected after that period of time.
Thermodynamic equilibrium between two isomers of imine
1 is reached even faster in CD3OD comparing with that in
CDCl3 and [2H6]DMSO. Two broad 9-H singlets of different
14 M. J. Frish, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, V. G. Zakrzewski, J. A. Montgomery, R. E. Stratmann,
J. C. Burant, S. Dapprich, J. M. Millam, A. D. Daniels, K. N. Kudin,
M. C. Strain, O. 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, D. K. Malick, A. D. Rabuck,
K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V. Ortiz, B. B. Stefanov,
G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin,
D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
C. Gonzalez, M. Challacombe, P. M. W. Gill, B. G. Johnson, W. Chen,
M. W. Wong, J. L. Andres, M. Head-Gordon, E. S. Replogle and
J. A. Pople, GAUSSIAN 98, Gaussian Inc., Pittsburgh, PA, 1998.
15 R. G. Parr and W. Yang, Density Functional Theory of Atoms and
Molecules, Oxford University Press, Oxford, 1989.
16 C. T. Lee, W. T. Yang and R. G. Parr, Phys. Rev. B, 1988, 37, 785.
17 K. Wolinski, J. F. Hinton and P. Pulay, J. Am. Chem. Soc., 1990, 112,
49.
18 G. Cottone, R. Noto and G. La Manna, Molecules, 2008, 13, 1246.
19 V. F. Traven, V. S. Miroshnikov, T. A. Chibisova, V. A. Barachevsky,
O. V. Venidiktova and Yu. P. Strokach, Izv. Akad. Nauk, Ser. Khim.,
2005, 2342 (Russ. Chem. Bull., Int. Ed., 2005, 54, 2417).
1
intensities can be seen in H NMR spectrum immediately after
the dissolving of imine 1. The signal at 8.94 ppm with higher
intensity corresponds to E-isomer, whereas lower intensity signal
at 9.06 ppm belongs to Z-isomer. Ratio of intensities of these
signals does not change in time. Absence of splitting of these two
signals is very likely to be due to fast H/D exchange of NH
proton in ketoenamine forms in CD3OD.
The behaviour of imine 2 in organic solvents is somewhat
different from that of imine 1. Two 9-H proton doublets
1
appear in H NMR spectra of 2 recorded both in CDCl3 and
in [2H6]DMSO immediately after preparation of the solution.
Intensity of high-field signal at 8.5 ppm (E-isomer) is higher
than low-field signal at 8.68 ppm (Z-isomer). Ratio of intensities
changes slightly in different solvents and is near to 65:35.
The NH signal of E-isomer is observed at 12.2 ppm, whereas
analogous signal of Z-isomer is seen at 10.5 ppm. Ratio of the
signals that belong to E- and Z-isomers remains unchanged
with time. Two broad signals are exhibited in 1H NMR spectrum
of imine 2 solution in CD3OD. Ratio of their intensities is also
remained unchanged after preparation of the solution.
20 J. Berthet, S. Delbaere, L. M. Carvalho, G. Vermeersch and P. J. Coelho,
Tetrahedron Lett., 2006, 47, 4903.
21 J. Hobley and V. Malatesta, Phys. Chem. Chem. Phys., 2000, 2, 57.
A few examples of E/Z-isomerization around the C=C bond
induced by solvents have been reported. All deal with enamine
structures.19–21 Earlier, we found that indoline merocyanines
derived from 3-formyl-4-hydroxycoumarins exist as mixtures
Received: 21st January 2009; Com. 09/3270
– 216 –