Photoreaction of cinnamate with nitrogen monoxide catalyzed by metallosalen complexes

Article abstract of DOI:10.1246/bcsj.75.2025

Ethyl cinnamate was allowed to react with nitrogen monoxide (NO) by photoirradiation in the presence of metallosalen complexes (4), oxygen, and axial ligands for 4 to yield furoxan derivatives (6). Oxygen and axial ligands are indispensable for this react

Full text of DOI:10.1246/bcsj.75.2025

c. Jpn.
© 2002 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 75, 2025–2029 (2002) 2025
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Photoreaction of Cinnamate with Nitrogen Monoxide Catalyzed by
Metallosalen Complexes
Photoreaction of Cinnamate with Nitrogen Monoxide
Y. Furusho et al.
Yoshio Furusho, Yow-hei Sohgawa, Nobuhiro Kihara, and Toshikazu Takata*
02
25
29
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University,
Gakuen-cho 1-1, Sakai, Osaka 599-8531
SJA8
09-2673
002
(Received January 7, 2002)
Ethyl cinnamate was allowed to react with nitrogen monoxide (NO) by photoirradiation in the presence of metal-
losalen complexes (4), oxygen, and axial ligands for 4 to yield furoxan derivatives (6). Oxygen and axial ligands are in-
dispensable for this reaction. Photoirradiation enhanced the yield of 6. Lowering the reaction temperature increased the
yield of 6 up to 55% (at −5 °C).
02
02
.3
Nitrogen monoxide (NO) is a gaseous diatomic molecule
with a free-radical nature consisting of a nitrogen atom and an
oxygen atom.1 Although NO is expected to be a simple nitro-
genating agent for organic compounds, its application to or-
ganic synthesis is limited due to a difficulty to control its reac-
tivity. Transition metal complexes have been successfully used
to control radical reactions in organic synthesis and polymer-
ization.2 For example, bis(1,3-diketonato)–transition metal
complexes were employed by Yamada et al. as catalysts for ni-
trogenation using NO.3
Salen-transition metal complexes have been extensively de-
veloped for organic synthesis, and have continued to be com-
plexes of great interest.4 We have recently proposed a rational
design of helical molecules utilizing the planarity of salen
complexes; we synthesized artificial helical polymers from
3,3ꢀ-diformylbinaphthol derivatives, diamines, and transition-
metal salts, and confirmed their helical structures.5 We have
also disclosed that the chiral space provided by the helical
poly(binaphthyl zinc–salen complex)es is effective for the
asymmetric addition of diethylzinc to benzaldehyde.5a As a
part of our program to develop polymeric metallosalen com-
plexes having helical structures, we have investigated the catal-
ysis of the corresponding monomeric metallosalen complexes
in organic synthesis. In the course of the study, we found that
some metallosalen complexes could catalyze the photoreaction
of cinnamates with NO to form furoxan derivatives. Furoxans
are known to be useful synthetic precursors for diamines, ni-
triles, and quinoxaline di-N-oxides, and have a wide range of
biological activities.6 Herein, we report on the photoreaction
of ethyl cinnamate with NO catalyzed by metallosalen com-
plexes to form furoxan derivatives.
(3).8 Condensation between 3 and ethylenediamine afforded
the corresponding Schiff base (4).8a Copper, cobalt, and man-
ganese ions were introduced by treating 4 with the correspond-
ing metal acetate to give metallosalen complexes (4-M).
Reaction of Ethyl Cinnamate with Nitrogen Monoxide in
the Presence of Oxygen. The reaction of ethyl trans-cin-
namate and nitrogen monoxide was investigated (Table 1).
Stirring a THF solution of ethyl cinnamate under an NO atmo-
sphere at room temperature without catalyst gave a nitrated
product (5), as reported by Yamada et al.9 In this case, no E/Z
selectivity was observed (E:Z = ca. 50:50, entry 1). In the
presence of oxygen, no product was formed from ethyl cin-
namate even in the presence of 4-Cu (entry 2). However, the
addition of pyridine as an axial ligand for 4-Cu yielded a
furoxan derivative (6)10 (entry 3). Photoirradiation (150-W Xe
lamp) increased the yield of 6, together with the formation of
epoxide (7) and ethyl cis-cinnamate (8) (entry 4). Imidazole
and pyridine N-oxide (PNO) gave similar results to that for py-
ridine (entries 5 and 6). Increasing the amount of PNO and ox-
ygen resulted in an increase in the yield of 6 (up to 30%, en-
tries 6–9). In all cases, ethyl cinnamate was completely con-
sumed to yield 5–8 and other unidentified products.
The effect of catalyst on the yield of 6 was investigated, as
shown in Table 2. The use of 10 mol% of 4-Cu hardly
changed the yield (entry 2). This suggests that demetallation
of the copper complex occurred during the reaction due to the
formation of nitrous acid in situ (vide infra). Actually, the ob-
tained reaction mixture was proved to be acidic by a litmus pa-
per test. A further addition of 5 mol% of 4-Cu to the reaction
mixture over a period of 20 h yielded 6 in a higher yield of
42% (entry 3). The use of cobalt and manganese complexes
(4-Co and 4-Mn) gave 6 in lower yields (entries 4 and 5).
Other copper complexes, such as Cu(salen) (salen = N,Nꢀ-
disalicylideneethylenediamine) and Cu(acac)2, resulted in low-
er yields together with the formation of a considerable amount
of 5 (entries 7 and 8).
Results and Discussion
Synthesis of Metallosalen Complexes. The synthesis of
metallosalen complexes was carried out according to Scheme
1. The treatment of bis(MOM) ether (1)7 with n-BuLi and
DMF yielded monoformylated bis(MOM) ether (2),8 which
was deprotected under acidic conditions to give monoaldehyde
Solvent effects and temperature were examined, as shown in
Table 3. In THF, the yield of 6 was higher at −5 °C than at

2026 Bull. Chem. Soc. Jpn., 75, No. 9 (2002)
Photoreaction of Cinnamate with Nitrogen Monoxide
Scheme 1. Synthesis of metallosalen complexes 4-M: (i) n-BuLi, DMF/THF, (ii) HCl, i-PrOH/CH2Cl2, (iii) ethylenediamine/ben-
zene, (iv) M(OAc)2/CH2Cl2.
Table 1. Reaction of Ethyl Cinnamate with Nitrogen Monoxide
Yield/%b),c)
Entry
Catalyst
Ligand (mol%) O2 (mol%)
hva)
5
7
0
0
0
0
0
0
0
0
6
7
0
0
0
3
5
5
4
1
1
8
0
0
0
7
7
5
5
5
4
1
2
3
4
5
6
7
8
9
none
4-Cu
4-Cu
4-Cu
4-Cu
4-Cu
4-Cu
4-Cu
4-Cu
none
none
100
100
150
150
150
150
150
400
none
none
none
irrad.
irrad.
irrad.
irrad.
irrad.
irrad.
0
0
4
10
8
11
20
19
30
none
pyidine (5)
pyidine (5)
imidazole (5)
PNOd) (5)
PNO (10)
PNO (30)
PNO (30)
a) 150-W Xe lamp with Pyrex filter. b) Determined by GC. c) In all case, ethyl cinnamate was consumed
completely to yield 5–8 and other unidentified products. d) pyridine N-oxide.
room temperature, although the reaction at −5 °C yielded 13%
of 5 to reduce the selectivity of 6 (entry 2). The lowered selec-
tivity is attributed to the higher solubility of NO (or N2O3) gas
to THF at lower temperatures. 1,2-Dichloroethane (1,2-DCE)
gave 6 in 40% yield at room temperature (entry 3). The forma-
tion of 5, however, dominated over that of 6 at −5 °C (entry 4).
The use of pyridine as a solvent resulted in a low yield of 6
(entry 5).
The reaction mechanisms for the formation of the furoxan
derivative (6), epoxide (7), and cis-cinnamate (8) are proposed
as shown in Scheme 2. Nitrogen monoxide is known to react
with oxygen to form dinitrogen trioxide, which should be the
actual NO source (Eq. 1).1 The reaction starts from the coordi-
nation of cinnamate to the metal complex (M(4)L) to form
complex A. The coordination is promoted by photoirradiation.
The activated olefin moiety of A nucleophilically attacks at
dinitrogen trioxide to form mononitroso complex B, which
was deprotonated to form the carbene complex C. Complex C
further attacks nucleophilically at dinitrogen trioxide to form
dinitroso complex D, which undergoes β-elimination to give
the furoxan derivative (6). The formation of ethyl cis-cin-
namate 8 is attributable to the E/Z isomerization of complex A.
The metal complex (M(4)L) is oxidized to the corresponding
oxo complex (OwM(4)L), which acts as an epoxidation agent

Y. Furusho et al.
Bull. Chem. Soc. Jpn., 75, No. 9 (2002) 2027
Table 2. Effect of Catalyst
Experimental
General: Melting points were measured on aYanagimoto mi-
cro melting-point apparatus and were uncorrected. IR spectra
were recorded on a JASCO FT-IR model 230 spectrometer. 1H
and 13C NMR measurements were performed on JEOL JNM-GX-
270 and JNM-L-400 spectrometers in CDCl3 with tetramethylsi-
lane as an internal reference. FAB-MS measurements were per-
formed on a Finnigan TSQ-70 instrument. Gas chromatographic
analyses were performed on a Shimadzu model GC 14A with a
flame-ionization detector and a capillary column CBP20-M25-
025. Photoirradiation was performed on an L5662-04 apparatus
(Hamamatsu, Co. Ltd.) with a 150-W xenon lamp.
Yield/%c),d)
Entry Catalyst (mol%)
5
0
0
0
0
0
47
20
6
7
1
1
2
0
0
0
0
8
4
3
2
2
1
0
0
1
2
3
4
5
6
7
4-Cu (5)
4-Cu (10)
30
33
42
27
31
25
2
4-Cu (5 + 5)a)
4-Co (5 + 5)a)
4-Mn (5 + 5)a)
Cu(salen)b) (5)
Cu(salen)2 (5)
Preparation of Metallosalen Complexes:
(R)-2,2ꢀ-Bis-
(methoxymethoxy)-1,1ꢀ-binaphthyl (1) was prepared from (R)-
1,1ꢀ-bi(2-naphthol) (> 99.9% ee, Kankyo Kagaku Co. Ltd.) ac-
cording to the procedure reported by Katsuki et al.7
a) Addition of further 5 mol% of the catalyst over the period
of 20 h to the reaction mixture which originally contained 5
mol% of the catalyst. b) salen = N,Nꢀ-disalicylideneethyl-
enediamine. c) Determinied by GC. d) In all case, ethyl
cinnamate was consumed completely to yield 5–8 and other
unidentified products. e) pyridine N-oxide.
(R)-2,2ꢀ-Bis(methoxymethoxy)-1,1ꢀ-binaphthyl-3-carbalde-
hyde (2):8 To a THF solution (32 mL) of bis(MOM ether) (1)
(3.00 g, 8.01 mmol) was added dropwise a hexane solution of n-
BuLi (1.6 M, 5.0 mL, 8.0 mmol) at room temperature. The result-
ing greenish yellow solution was stirred for additional 25 min. To
this mixture was added DMF (586 mg, 8.01 mmol), and the solu-
tion was stirred at room temperature for 1 h. Then, sat. aq NH4Cl
was added to the mixture. The mixture was extracted with ben-
zene. The extract was washed successively with sat. aq NaHCO3
and brine, dried over anhydrous MgSO4, and evaporated to dry-
ness. The residue was purified with silica-gel chromatography
(benzene:ether = 20:1) to give the corresponding monoaldehyde
(2) as a white crystal (2.67 g, 83%). Mp 133.5–134.0 °C. 1H
NMR (400 MHz, CDCl3) δ 10.58 (s, 1H, CHO), 8.56 (s, 1H,
ArH), 8.10–7.85 (m, 3H, ArH), 7.65–7.10 (m, 7H, ArH), 5.10
(ABq, J1 = 33 Hz, J2 = 7 Hz, 2H, OCH2OCH3), 4.69 (ABq, J1 =
33 Hz, J2 = 7 Hz, 2H, OCH2OCH3), 3.16 (s, 3H, OCH3), 2.99 (s,
3H, OCH3).
Table 3. Effects of Solvent and Temperature
Yield/%b),c)
Entry
Solvent
THF
Temp/°C
5
0
13
0
42
0
6
7
2
0
1
0
0
8
2
0
2
0
1
1
2
3
4
5
rt
42
55
40
35
25
THF
−5 °C
rt
−5 °C
rt
1,2-DCEa)
1,2-DCEa)
pyridine
(R)-2,2ꢀ-Dihydroxy-1,1ꢀ-binaphthyl-3-carbaldehyde
(3):8
To a dichloromethane solution (50 mL) of bis(MOM ether) (2)
was added a mixture of conc. HCl (20 mL) and i-PrOH (80 mL).
The mixture was stirred at room temperature for one day, and then
extracted with chloroform. The extract was washed with water,
dried over anhydrous MgSO4, and evaporated to give the dihy-
droxy compound (3) as a yellow solid (8.4 g, 97%). Mp 213–220
°C. 1H NMR (270 MHz, CDCl3) δ 10.62 (s, 1H, CHO), 10.21 (s,
1H, OH), 8.39 (s, 1H, ArH), 8.00–7.85 (m, 4H, ArH), 7.45–7.05
(m, 6H, ArH), 4.91 (s, 2H, OH).
a) 1,2-dichloroethane. b) Determined by GC. c) In all case,
ethyl cinnamate was consumed completely to yield 5–8 and
other unidentified products. d) pyridine N-oxide.
for the olefin to give the corresponding epoxide 7.
This reaction was applied to ethyl crotonate as an aliphatic
conjugated ester to investigate the potential utility of this reac-
tion as a synthetic method for furoxan derivatives. The pho-
toirradiation of a mixture of ethyl crotonate, 4-Cu (10 mol%),
PNO (30 mol%), and O2 (400 mol%) in THF under an NO at-
mosphere afforded the corresponding furoxan derivative
(9)10,11 in 39% yield (Scheme 3). This result suggests that this
protocol would be useful for preparing other furoxan deriva-
tives.
In summary, the reaction of ethyl cinnamate with NO cata-
lyzed by Cu-salen complex (4-Cu) was investigated in this
work. The oxygen molecule and axial ligands for the complex
are necessary for the furoxan formation. Photoirradiation en-
hances the yield of furoxan derivative (6). The use of other
metallosalen complexes, such as Cu(salen), resulted in a de-
crease in the yield of 6. In the reaction at −5 °C, the highest
yield of 6 was 55%. The application of this procedure to ethyl
crotonate afforded the corresponding furoxan derivative (9).
(R,R)-BINOL-Schiff Base (4):8a
A benzene solution (30
mL) of monoaldehyde (3) (10.0 g, 23.2 mmol) and ethylenedi-
amine (775 µL, 11.6 mmol) was refluxed overnight while remov-
ing water with a Dean–Stark apparatus. The solution was evapo-
rated to dryness. The residue was recrystallized from CH2Cl2/hex-
ane to give the title compound (4) (6.81 g, 90%). Mp 198–201 °C.
1H NMR (270 MHz, CDCl3) δ 13.27 (s, 2H, OH), 8.61 (s, 2H,
ArCHwN), 7.95–7.82 (m, 10H, ArH), 7.35–7.06 (m, 12H, ArH),
5.06 (s, 2H, OH), 3.97 (ABq, J1 = 9.7 Hz, J2 = 2.7 Hz, 4H,
CH2N). IR (KBr) 3413 (νO-H), 1633 (νCwN) cm−1
.
(R,R)-Cuꢁ-BINOL-Salen Complex (4-Cu): To a CH2Cl2 so-
lution (20 mL) of 4 (1.31 g, 2.00 mmol) was added Cu(OAc)2•
H2O (400 mg, 4.00 mmol). The mixture was refluxed for 3 h and
then filtered off. The filtrate was poured into hexane and the pre-
cipitate was collected by suction filtration. The crude product was
purified by reprecipitation from THF/pentane to give the title
compound (4-Cu) as a dark-brown powder (93%). Mp > 300 °C.

2028 Bull. Chem. Soc. Jpn., 75, No. 9 (2002)
Photoreaction of Cinnamate with Nitrogen Monoxide
Scheme 2. A possible reaction mechanism for the formation of furoxan 6–8.
Scheme 3. Reaction of ethyl crotonate with nitrogen monoxide.
FT-IR (KBr) 1614 (νCwN) cm−1. FAB-MS (matrix: mNBA) m/z
30-mL three-necked flask (Pyrex) with a gas syringe (used as a
pressure equalizer), a stopcock, and a light guide cap under an Ar
atmosphere. An Ar atmosphere was substituted for nitrogen mon-
oxide gas (1 atm). To the flask was introduced gaseous oxygen
(90 mL, 4.0 mmol). The mixture was irradiated with a 150-W xe-
non lamp for 24 h. The reaction progress was monitored by GC
using hexadecane as an internal standard. The reaction mixture
was poured into hexane and filtered off. The residue was purified
by SiO2 chromatography.
3 (or 4-)-Ethoxycarbonyl-4- (or 3-) phenyl-1,2,5-oxadiazole
2-Oxide (6):10 Colorless oil. 1H NMR (270 MHz, CDCl3) δ
7.98–7.43 (m, 5H, ArH), 4.38 (q, J = 7.3 Hz, 2H, CH2CH3), 1.26
(t, J = 7.3 Hz, 3H, CH2CH3). 13C NMR (67.5 Hz, CDCl3) δ
156.3, 155.9, 133.0, 131.0, 129.2, 128.5, 108.2, 63.0, 13.9. FT-IR
(film) 2986, 1738 (νCwO), 1606 (νCwNwO), 1479 (νNO2), 1455 (νNO2),
1328, 1203 cm−1. EI-MS (70 eV) m/z 234 ([M]+, 9.2), 204 ([M −
NO]+, 18.0), 174 ([M − 2NO]+, 19.0).
714 [(M + H)+]. Found: C, 72.3; H, 4.5; N, 3.9%. Calcd for
C44H30N2O4•H2O: C, 72.2; H, 4.4; N, 3.8%.
(R,R)-Coꢁ-BINOL-Salen Complex (4-Co): The title com-
pound (4-Co) was prepared from an equimolar amount of 4 and
Co(OAc)2•4H2O in a similar manner to that for 4-Cu (dark-green
powder, 92%). Mp > 300 °C. FT-IR (KBr) 1616 (νCwN) cm−1
FAB-MS (matrix: mNBA) m/z 710 [(M + H)+].
.
(R,R)-Mnꢂ-BINOL-Salen Complex (4-Mn): The title com-
pound (4-Mn) was prepared from an equimolar amount of 4 and
Mn(OAc)2•4H2O in a similar manner to that for 4-Cu (black pow-
der, 93%). Mp > 300 °C. FT-IR (KBr) 1612 (νCwN) cm−1. FAB-
MS (matrix: mNBA) m/z 705 [M+].
A Typical Procedure for the Reaction of Ethyl Cinnamate
with Nitrogen Monoxide: A THF solution (3 mL) of ethyl cin-
namate (176 mg, 1.0 mmol), 4-Cu (34 mg, 50 µmol), pyridine N-
oxide (29 mg, 0.30 mmol), and hexadecane (10 mg) was put into a

Y. Furusho et al.
Bull. Chem. Soc. Jpn., 75, No. 9 (2002) 2029
3-Ethoxycarbonyl-4-methyl-1,2,5-oxadiazole 2-Oxide
(9):10,11 yellow oil. 1H NMR (270 MHz, CDCl3) δ 4.30 (q, J =
7.2 Hz, 2H, OCH2CH3), 2.48 (s, 3H, CH3), 1.33 (t, J = 7.2 Hz,
3H, OCH2CH3).
3
a) For a review, see: E. Hata, K. Kato, T. Yamada, and T.
Mukaiyama, J. Synth. Org. Chem., Jpn., 54, 728 (1996). b) K.
Kato and T. Mukaiyama, Chem. Lett., 1990, 1395. c) T.
Mukaiyama, K. Yorozu, K. Kato, and T. Yamada, Chem. Lett.,
1992, 181.
4
For a review, see: D. A. Atwood and M. J. Harvey, Chem.
This work was financially supported by Sumitomo Founda-
tion, Nissan Science Foundation, and Mitsubishi-Yukakagaku
Chemistry Foundation, which are greatly acknowledged. We
are grateful to Professor F. Sanada of Kyoto University for the
elemental analysis.
Rev., 101, 37 (2001).
5
a) Y. Furusho, T. Maeda, T. Takeuchi, N. Makino, and T.
Takata, Chem. Lett., 2001, 1020. b) T. Maeda, Y. Furusho, and T.
Takata, Chirality, 14, 587 (2002).
6
A. Gasco and A. J. Boulton, in “Advances in Heterocyclic
Chemistry,” ed by A. R. Katritzky and A. J. Boulton, Academic
Press, New York (1981), Vol. 29, p. 251.
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