Photoisomerization of ionic liquid ammonium cinnamates: One-pot synthesis-isolation of Z-cinnamic acids

Article abstract of DOI:10.1021/ol1019508

Photoisomerization presents the only direct method for contra-thermodynamic E-Z isomerization of olefins. Synthetic applications of this method have been limited by its reversible nature, which leads to a photostationary-state mixture of both isomers. For the first time, a highly efficient one-pot preparation-isolation of solid ionic liquid Z-cinnamic acids by photoisomerization in acetonitrile solution of ionic liquid E-cinnamic acids is described.

Full text of DOI:10.1021/ol1019508

ORGANIC
LETTERS
2010
Vol. 12, No. 21
4808-4811
Photoisomerization of Ionic Liquid
Ammonium Cinnamates: One-Pot
Synthesis-Isolation of Z-Cinnamic
Acids
Mar´ıa L. Salum, Cecilia J. Robles, and Rosa Erra-Balsells*
CIHIDECAR-Departamento de Qu´ımica Orga´nica, FCEN, UniVersidad de Buenos
Aires, Pabello´n II, 3er P, Ciudad UniVersitaria. 1428 - Buenos Aires, Argentina
erra@qo.fcen.uba.ar
Received August 18, 2010
ABSTRACT
Photoisomerization presents the only direct method for contra-thermodynamic E-Z isomerization of olefins. Synthetic applications of this
method have been limited by its reversible nature, which leads to a photostationary-state mixture of both isomers. For the first time, a highly
efficient one-pot preparation-isolation of solid ionic liquid Z-cinnamic acids by photoisomerization in acetonitrile solution of ionic liquid
E-cinnamic acids is described.
Ionic liquids (ILs) are nanostructured compounds whose
properties can be tuned by variation of the cation and
anion nature.1 There are countless combinations possible,
which make ILs well suited to creating tailor-made or
“designed compounds” with different densities, viscosities,
polarity, optical properties, etc.1 As part of a project
related to the study of the photochemical stability of ILs
for application as matrixes in matrix-assisted laser de-
sorption/ionization mass spectrometry,2a,b several ILs (E-
CHAm) were prepared combining commercially available
E-cinnamic acids (E-CH) (Scheme 1(a), E-1, E-2, E-3, E-4,
and E-5) and organic bases (Am) (Scheme 1(b), Am ) a-i),
i.e., E-1a, E-1b, E-2a, and E-2b, etc. (E-CHAm; see Scheme
1(c)). The photostability of the E-CHAm was studied in
MeCN solution. To our surprise and good luck, we found a
one-pot method for the preparation-isolation as a solid,
without any additional chemical manipulation, of the cor-
responding IL Z-CHAm (Scheme 2). From Z-CHAm, the
(2) (a) Armstrong, D. W.; Zhang, L.-K.; He, L.; Gross, M. L. Anal.
Chem. 2001, 73, 3679. (b) Crank, J. A.; Armstrong, D. W. J. Am. Soc.
Mass Secptrom. 2009, 20, 1790.
(1) Wassescheid, P.; Keim, W. Angew. Chem., Int. Ed. Engl. 2000, 39,
3772.
10.1021/ol1019508  2010 American Chemical Society
Published on Web 09/28/2010

Scheme 1
.
Substrates Studieda
Scheme 3.
Z-Cinnamic Acids (Z-CH) Prepareda
a Characterization of Z-CH is described in the Supporting Information.
exploring the possible physiological roles played by Z-CH
that still are not known, it is essential to have these
compounds commercially available and/or simple and friendly
protocols for their preparation-isolation and purification.3c
Photochemical E-Z isomerization is a major area of
interest in modern photochemical research and is also studied,
as a special tool for synthesis, in preparative organic
photochemistry.4a-c It has a major role in many photobio-
logical phenomena.4a-c It has practical application in
industry4d and in many optoelectrical, optomechanical switch-
ing, storage devices, and light-driven chiroptical molecular
motors.4e,f Synthetic applications of this method have been
limited by its reversible nature, which, in the absence of other
reactions, leads to a photostationary-state mixture of both
isomers in solution (Scheme 2).4a-c,5a,b The composition of
these mixtures is governed by different factors,4a-c,5a,b and
there are few citations for the efficient photochemical E to
Z one-way isomerization process.4c,6a,b
a Detailed nomenclature, preparation, and charaterization of E-CHAm
are described in the Supporting Information.
corresponding Z-cinnamic acid (Z-CH, Scheme 3) could be
easily obtained by pH adjusting a Z-CHAm methanol
solution.
Herein we report for the first time a highly efficient one-
pot preparation-isolation of solid Z-CHAm by photoisomer-
ization in MeCN solution of the corresponding E-CHAm
(Scheme 2).
Irradiation of 0.01 M E-1 in acetonitrile solution with a
Pyrex-filtered high-pressure mercury lamp (λem >300 nm)
or monochromatic light (313 nm) results in the formation
of a photostationary state consisting of 67% E-1 and 33%
Z-1. Photodimerization does not compete with E/Z isomer-
Scheme 2. Photoreaction Studied
(4) For selected reviews on cis-trans photoisomerization and its
applications: (a) Mori, T.; Inoue, Y. In CdC Photoinduced Isomerization
Reactions; Griesbeck, A. G., Mattay, J., Eds.; Synthetic Organic Photo-
chemistry; Marcel Dekker: New York, 2005; p 417. (b) Arai, T. In
Photochemical cis-trans Isomerization in the Triplet State; Ramamurthy,
V., Schanze, K. S., Eds.; Organic Molecular Photochemistry, in the Series,
Molecular and Supramolecular Photochemistry, 1999; Vol 3, p 131. (c)
Rao, V. J. In Photochemical cis-trans Isomerization from the Singlet State,
Ramamurthy, V.; Schanze, K. S., Eds.: Organic Molecular Photochemistry,
in the Series, Molecular and Supramolecular Photochemistry, 1999; Vol
3, 169. (d) Braun, A. M.; Maurette, M. T.; Oliveros, E. Photochemical
Technology; Wiley-Chichester, 1991; p 500. (e) Nieuwendaal, R. C.;
Bertmer, M.; Hayes, S. E. J. Phys. Chem. B 2008, 112, 12920. (f) Feringa,
B. L.; van Delden, R. A.; Koumura, N.; Geertsema, E. M. Chem. ReV. 2000,
Cinnamic acids exists in both E- and Z-forms in nature.
Thus, interest in both isomers has increased because they
were detected in all kinds of plant-derived products: i.e.,
foods, herbs medicines, cosmetics, etc.3a,b The role of E-CH
in plant and mammal cells has been extensively studied
because they are commercially available.3a-c In contrast to
100, 1789
.
(5) (a) Klessinger, M.; Michl, J. Excited States and Photochemistry of
Organic Molecules; VCH Publishers, Inc.: New York, 1995; p 362. (b)
Turro, N. J.; Ramamurthy, V.; Scaiano, J. C. Principles of Molecular
Photochemistry: An Introduction ; University Science Books: Sausalito,
(3) For selected examples of biosynthesis and plant physiology, studies
of trans- and cis-cinnamic acids: (a) Caccamese, S.; Azzolina, R. Chro-
matographia 1979, 12, 545. (b) Wong, W. S.; Guo, D.; Wang, X. L.; Yin,
Z. Q.; Xia, B.; Li, N. Plant Physiol. Biochem. 2005, 43, 929, and references
therein. (c) Sun, F.-M.; Smith, J. L.; Vittimberga, B. M.; Traxler, R. W.
ACS Symp. Ser. 2002, 816, 228.
2009; p 319
.
(6) (a) Lewis, F. D.; Yang, J.-S. J. Phys. Chem. 1996, 100, 14560, and
references therein. (b) Raj Gopal, V.; Mahipal, A.; Reddy, V.; Rao, J. J.
Org. Chem. 1995, 60, 7966
.
Org. Lett., Vol. 12, No. 21, 2010
4809

ization under these conditions. Similar values of the photo-
stationary state are obtained in ethanol and methanol solution.
Irradiation of 0.01 M E-1a (prepared with E-1 and a, Scheme
1) in acetonitrile solution results in a photostationary state
consisting of 57% E-1a and 37% Z-1a (Table 1, entry 1)
together with a solid phase characterized as Z-1a in 20%
yield (Table 1, entry 1).
entry 4). To our surprise, no solid phase was formed during
the irradiation of the acetonitrile solution of E-1e (Scheme
1, e dielthylamine), E-1g (Scheme 1, g trielthylamine), E-1h
(Scheme 1, h tributylamine), and E-1i (Scheme 1, i N-
methylpiperidine). After irradiation, no solid phase was
obtained, although several attempts to induce precipitation
were made (i.e., irradiated solution kept at low temperature,
partial evaporation of the solvent). As an exception, irradia-
tion of the acetonitrile solution of E-1d (Scheme 1, d
2-phenylethylamine) afforded Z-1d contaminated with E-1d
as precipitate (Table 1, entry 5).
Table 1. Results Obtained by UV-Irradiation of Ionic Liquids of
E-Cinnamic Acids (E-CHAm) in MeCN Solution: Substrate
Scope
As is depicted in Table 1, the photoisomerization IL
E-1-IL Z-1 is the major process that occurs in solution. A
minor decarboxylation reaction was also observed in some
cases with the aryl-ethene compound formed in solution
remaining (Table 1, entries 1, 2, 6, and 7). The acetonitrile
solution of each IL prepared with E-1 and the above-
mentioned bases (a-i; Scheme 1(b)) were shown to be stable
kept in the dark at room temperature.
products in
product
solution yield [%]a precipitated yield [%]b
entry ionic liquid E-CHAm Z-CHAm
Z-CHAm
1
2
3
4
5
6
7
8
E-1a
E-1b
E-1c
E-1cd
E-1d
E-1f
57c
73c
55
93
66
37
21
45
7
20
26
30
68
39e
33
-
Furthermore, we have explored the substrate scope of the
reaction using different E-cinnamic acids (E-CH, see details
in Scheme 1 and Table 1). Irradiation of E-2 in acetonitrile
solution showed the formation of a photostationary state
consisting of 53% E-2 and 47% Z-2. Irradiation of E-2a in
acetonitrile solution results in a photostationary state consist-
ing of 44% E-2a and 51% Z-2a (Table 1, entry 8) together
with 5% of the corresponding decarboxylated product. Any
solid precipitated was obtained, although several attempts
to induce it were made. Similar results were obtained by
irradiation of E-2Am with Am ) e-i (some results are listed
in Table 1, entries 14 and 15). As shown in Table 1,
conversion of E-2Am to solid Z-2Am in situ, during the
irradiation process, was observed with E-2b and E-2c,
showing the latter with optimum conversion value (Table 1,
entries 9-12). As it was previously observed, irradiation of
the acetonitrile solution of the E-CHAm containing d (2-
phenylethylamine) in its structure, E-2d (Scheme 1), afforded
Z-2d contaminated with E-2d as precipitate (Table 1, entry
13).
34
26
35
51
34
50
15
25
46
67
46
36
31
79
60
7
68c
60c
44c
63c
45c
78
E-1i
E-2a
E-2b
E-2bd
E-2c
E-2cd
E-2d
E-2f
-
9
12
21
26
56
25e
-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
75
50c
29c
50c
57c
69
E-2i
-
E-3a
E-3b
E-3c
E-3f
E-4a
E-4b
E-4c
E-4f
31
32
-
21
40
93
86
94
97
58
19e
29
-
14
6
3
-
-
40
E-5a
42
a Determined by 1H NMR spectroscopic analysis of the irradiated
solution. b The yields are based on the conversion of the starting material
(E-CHAm). c Low yield of the decarboxylated product (aryl-alkene, 3-7%)
in solution is observed. d Reirradiation of the mother liquor after solid
Z-CHAm was filtered off. e Solid Z-CHAm is obtained contaminated with
E-CHAm.
From the analysis of the above results, we envisioned that
the basic character of the amine used to prepare the IL
E-CHAm is not the only reason for the low solubility in the
irradiated solution of the IL Z-CHAm formed and its specific
precipitation as a pure solid compound (Scheme 2). The
molecular structure of both the cinnamic acid (CH) and the
amine (Am) would be the cause of this special behavior.
The effect of varying the amine on the optimum conver-
sion of E-1 to Z-1 in acetonitrile solution is shown in Table
1. Conversions of 26%, 30%, and 33% of the starting
material E-1Am to Z-1Am, as a solid precipitate formed
during the irradiation, were observed with E-1b, E-1c, and
E-1f prepared with 4-amino-1-butanol (Scheme 1 and Table
1, entry 2), ethanolamine (Scheme 1 and Table 1, entry 3),
and piperidine (Scheme 1 and Table 1, entry 6). This
conversion increases noticeably (68%) when after filtering
the solid in suspension, i.e., Z-1c, the transparent solution
(mother liquor) was again irradiated until the solid phase
formation was observed. Thus, the efficiency of one-pot IL
E to IL Z photoconversion, yielding IL Z as a pure solid
compound, could be optimized by recycling (reirradiating)
the mother solution after the solid was filtered off (Table 1,
We hypothesized that the end terminal structure of the
amine would approach the aromatic moiety (aryl group) of
the cinnamic acid structure in a synclinal overlapping fashion
to provide the required distance among functional groups to
generate stabilizing intramolecular (intra-IL-molecular) in-
teractions such as hydrogen bridge or hydrophobic-
hydrophobic interactions. As is shown in Figures 1 and 2,
after the E to Z photoisomerization, this approach can easily
occur in one of the rotamers formed by the Z-CHAm (Figure
2, structure on the right; molecular modeling details are
included in the Supporting Information). This is the first level
of control of E-CHAm to Z-CHAm in a one-way photocon-
4810
Org. Lett., Vol. 12, No. 21, 2010

Figure 2. Proposed rotamer structure for Z-CHAm: soluble forms
(left and middle) and lower soluble form (right). As an example,
Z-2c.
Figure 1. E-Z photoisomerization of ionic liquid cinamic acids
(E-CHAm/Z-CHAm). As an example, E-2c/Z-2c.
a pure solid precipitate was obtained by photoisomerization
of E-5a, E-5b, and E-5c. The optimum conversion was
obtained with E-5a (Table 1, entry 24).
version with selective Z-CHAm solid formation (precipita-
tion) (Scheme 2). This level of control is imparted through
the irradiated substrate itself. A second level of control
of the process can be imparted through the medium itself;
i.e., the capability of the solvent to compete, as a protic
solvent, providing a source of intermolecular hydrogen
bridge, would stabilize other rotamer structures of the
Z-CHAm soluble in polar protic media. Soluble photosta-
tionary E-CHAm-Z-CHAm mixtures were obtained in
methanol and in ethanol solution. Besides, Z-CHAm obtained
as precipitate during irradiation requires acetontrile-methanol
mixtures enriched in methanol (higher % of methanol) for
complete dissolution. Furthermore, irradiation of this solution
yielded the completely soluble photostationary state of a
Z-CHAm-E-CHAm mixture from which any of the com-
ponents could be isolated as a pure solid compound.
To explore the potential application of these principles
to the one-pot preparation-isolation of Z-CHAm, we
chose two cinnamic acids, p-coumaric acid E-3 (Scheme
1(a)) with the hydroxyl group as the only substituent at
the C-4 position and cinnamic acid itself, E-4 (Scheme
1(a)), without any substituent in the aromatic ring. The
experiments were conducted, and as expected the reactions
proceeded for E-3Am similarly to what was observed for
E-1Am and E-2Am (Table 1, entries 16-19), with the best
results for E-3a and E-3b. To our delight, when we irradiated
E-4Am, only pure solid Z-4a was obtained as precipitated
from the irradiated solution in 29% yield (Table 1, entry 20)
when butylamine as base was used (hydrophobic-hydrophobic
stabilizing interaction). We then investigated the substrate
scope of the reaction using E-5, the methylene-3,4-dioxy
derivative of cinnamic acid (Scheme 1(a)). The methylene-
3,4-dioxy group fixing the electron-donating groups at the
meta- and para-positions creates in this portion of the
cinnamic molecule an electronic environment similar to that
of E-1 (see structures in Scheme 1(a)). Thus, the Z-5Am as
In summary, we have developed the first one-pot
preparation-isolation of a pure Z-cinnamic acid (Z-CH)
precursor by simple E-Z photoisomerization of ionic liquids
E-CHAm whose anion is the corresponding E-cinnamic acid
(E-CH). The IL is prepared choosing a commercial simple
primary amine (Am) with the proper end terminal group (i.e.,
butylamine, ethanolamine, etc.). This selection depends on
the nature of the substituents located in meta or para
positions, or both, in the E-CH structure. The selective
formation of the solid pure Z-IL (Z-CHAm) during the
irradiation only takes place if irradiation is conducted in
MeCN. Both result in a strong outcome suggesting that an
intra-IL-molecular interaction affected by the solvent nature
is operating. We propose that within the different rotamer
structures of Z-CHAm only few are stabilized by intramo-
lecular hydrogen bonding. Because of this, closed rotamers
show minimum interaction with the medium precipitate as
pure Z-CHAm. Additional studies exploring this E/Z pho-
tochemical one-pot preparation-isolation of pure ionic liquid
Z isomers in the field of 3-aryl-acrylic acids are currently
underway, and the results will be reported in due course.
Acknowledgment. We are grateful to CONICET (PIP
00400), ANPCyT (PICT 06-615), and UBA (X072) for
support of this research. M.L.S. and R.E.-B. are research
members of CONICET.
Supporting Information Available: Experimental pro-
cedures, spectroscopic data for IL, 1H NMR spectra, and full
characterization data for E- and Z-cinnamic acids. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL1019508
Org. Lett., Vol. 12, No. 21, 2010
4811