Improved efficiency and product selectivity in the photo-Claisen-type rearrangement of an aryl naphthylmethyl ether using a microreactor/flow system

Article abstract of DOI:10.1007/s11164-012-0650-6

Ultraviolet (UV) irradiation of 2-[(2,4,6-trimethylphenoxy)methyl]-1- (methoxycarbonyl)naphthalene promotes a photochemical reaction that gives a cyclohexa-2,4-dienone product arising from a photo-Claisen-type ortho-rearrangement and a phenol derivative arising from a meta-rearrangement, along with 1-methoxycarbonyl-2-methylnaphthalene and 1,2-bis[1-(methoxycarbonyl) naphthalen-2-yl]ethane. When this process is carried out in a microreactor/flow system, its efficiency is dramatically enhanced and selectivity of products is improved. The effects on efficiency and product selectivity caused by the microreactor/flow system are attributed to more efficient light absorption and the suppression of secondary reactions.

Full text of DOI:10.1007/s11164-012-0650-6

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Res Chem Intermed (2013) 39:301–310
DOI 10.1007/s11164-012-0650-6
Improved efficiency and product selectivity
in the photo-Claisen-type rearrangement of an aryl
naphthylmethyl ether using a microreactor/flow system
•
Hajime Maeda Satoshi Nashihara
•
•
•
Hirofumi Mukae Yasuharu Yoshimi
Kazuhiko Mizuno
Received: 19 October 2011 / Accepted: 18 December 2011 / Published online: 13 June 2012
Ó Springer Science+Business Media B.V. 2012
Abstract Ultraviolet (UV) irradiation of 2-[(2,4,6-trimethylphenoxy)methyl]-
1-(methoxycarbonyl)naphthalene promotes a photochemical reaction that gives a
cyclohexa-2,4-dienone product arising from a photo-Claisen-type ortho-rearrange-
ment and a phenol derivative arising from a meta-rearrangement, along with
1-methoxycarbonyl-2-methylnaphthalene and 1,2-bis[1-(methoxycarbonyl)naphtha-
len-2-yl]ethane. When this process is carried out in a microreactor/flow system, its
efficiency is dramatically enhanced and selectivity of products is improved. The
effects on efficiency and product selectivity caused by the microreactor/flow system
are attributed to more efficient light absorption and the suppression of secondary
reactions.
Keywords Photoreaction ꢀ Photorearrangement ꢀ Photochemistry ꢀ
Microreactor ꢀ Flow system
Introduction
Photochemical rearrangements of organic substances have been used as important
synthetic methodologies. As a result, extensive studies have been carried out aimed
H. Maeda (&)
Division of Material Sciences, Graduate School of Natural Science and Technology,
Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan
e-mail: maeda-h@t.kanazawa-u.ac.jp
S. Nashihara ꢀ H. Mukae ꢀ K. Mizuno (&)
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University,
1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
e-mail: mizuno@chem.osakafu-u.ac.jp
Y. Yoshimi
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, University
of Fukui, 3-9-1 Bunkyo, Fukui, Fukui 910-8507, Japan
123

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302
H. Maeda et al.
at the elucidation of reaction mechanisms and the detection of key radical and
radical ion intermediates [1–5]. Photo-Claisen rearrangement reactions of allyl and
benzyl aryl ethers are representative of this family of processes [6–21]. These
studies have demonstrated that this excited-state reaction involves a pathway in
which initial homolytic C–O bond cleavage is followed by radical coupling
processes to yield both para- and ortho-substituted phenol derivatives. In recent
studies of photo-Claisen-type rearrangement reactions of aryl naphthylmethyl
ethers, we observed that a 2,4,6-trimethylphenoxy derivative reacts to form a
cyclohexa-2,4-dienone product arising from ortho-rearrangement along with a
reduced amount of the para-rearrangement product [22–25]. However, other side-
products are generated in this reaction by either subsequent acid-catalyzed
rearrangement of the cyclohexa-2,4-dienone product or following the escape of
intermediate radicals from solvent cage.
In recent years, microreactors that employ a flow system have become a powerful
tool for carrying out preparative organic photochemical reactions [26–50]. In an
earlier effort, we observed that use of a microreactor led to an enhancement in the
efficiency and product selectivity of an intramolecular photocycloaddition reaction
of a 1-cyanonaphthalene derivative [51, 52]. We concluded at that time that the
enhanced efficiency and product selectivity were a consequence of more complete
light absorption in the microreactor and rapid removal of the initially formed
photoproduct from the reactor due to the use of a flow system. In continuing studies
in this area described below, we have observed that the product selectivity of a
photo-Claisen-type rearrangement reaction of an aryl naphthylmethyl ether can also
be improved by using a microreactor/flow system.
Results and discussion
The general design of the microreactor/flow systems used for the photoreaction
explored in this study is shown in Fig. 1. Two types of microreactors (type A and
type B), both made of Pyrex glass and having the channel widths, depths, and
lengths shown in Fig. 1, were used. Solutions, containing the starting material, were
injected into the reactors by using a syringe pump (flow rate = 0.02–0.05 mL/h)
and irradiated by using a 300-W high-pressure mercury lamp only while flowing
through the microreactors. The residence time of the solution in the microreactor,
which is equal to the actual irradiation time, is calculated by using the equation
residence time ¼ irradiation time
volume of microchannel chip
¼
flow rate
In the batch system used for comparison, the unstirred sample solution in a
conventional cylindrical Pyrex tube was irradiated by using the same 300-W high-
pressure mercury lamp.
In the batch process, irradiation of a benzene solution containing 2-[(2,4,
6-trimethylphenoxy)methyl]-1-(methoxycarbonyl)naphthalene (1), carried out for
8 h, led to formation of the cyclohexa-2,4-dienone derivative 2 (22 %) as the
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Improved efficiency and product selectivity
303
Batch system
Light
Gastight Syringe
Microreactor
Syringe Infusion Pump
16 cm
Light
type A
type B
in
out
out
8.0 mm
in
material : Pyrex
width = 200 µm
depth = 90 µm
material : Pyrex
width = 100 µm
depth = 40 µm
2.6 cm
2.6 cm
length = 60 mm
length = 120 mm
volume = 1.08 mm3
volume = 0.48 mm3
7.6 cm
7.6 cm
Fig. 1 Apparatuses for the photoreactions
photo-Claisen-type rearrangement product along with the meta-rearrangement product
3 (19 %), 1-methoxycarbonyl-2-methylnaphthalene (4) (9 %), and the dimeric product
1,2-bis[1-(methoxycarbonyl)naphthalen-2-yl]ethane (5) (12 %) (Scheme 1, Table 1,
entry 1). When the same photoreaction was carried out using the type A microreactor/
flowsystem(flowrate0.03 mL/h), 75 % conversionof1 wasachievedinonlya 2.2 min
residence time. In addition, the products formed included 2 (33 %), 3 (25 %), and 5
(3 %) (entry 2). Importantly, the reaction time was dramatically shortened in
comparison with that using the batch system and the yield of 2 increased while the
formation of 4 and 5 was suppressed. A further increase in the 2/3 product ratio was
brought about by increasing the flow rate to 0.04–0.05 mL/h (entries 3, 4), but the
percent conversion of 1 decreased. These results and a desire to increase the conversion
of 1 prompted us to explore the reaction carried out in the type B microreactor,
whose channel length is twice as long as that in the type A apparatus but the depth is
much shallower (entries 5–7). By using an optimized flow rate at 0.03 mL/h in the
type B microreactor, reaction of 1 produced a 5.1/1 2/3 product ratio and 90 %
conversion of 1.
Plausible mechanistic pathways for the formation of the products in these
photoreactions are shown in Scheme 2. In these routes, irradiation of aryl
Table 1 Effect of microreactor on the photo-Claisen-type rearrangement of 1
Entry
Condition
Flow rate
(mL/h)
Residence
time (min)
Yieldsa (%)
Conversion
of 1a (%)
2
3
4
5
1
2
3
4
5
6
7
Batch
–
480
22b
33
21
18
26
51
40
19b
25
6
9b
12b
3
86b
75
69
56
63
90
96
Type A
Type A
Type A
Type B
Type B
Type B
0.03
0.04
0.05
0.04
0.03
0.02
2.16
1.62
1.30
0.75
1.00
1.50
Trace
Trace
Trace
1
2
6
1
9
2
10
14
1
2
1
7
[1] = 2.0 9 10-2 mol/L in benzene, rt, irradiated by a 300-W high-pressure mercury lamp
a
Determined by 1H nuclear magnetic resonance (NMR) spectroscopy
b
Determined by the amount of isolated products
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H. Maeda et al.
CO2Me
O
CO2Me
CO2Me
OH
h
(> 280 nm)
benzene
O
+
1
2
3
OH
CO2Me
CO2Me
+
+
+
CO2Me
4
5
6
Scheme 1 Photo-Claisen-type rearrangement of an aryl naphthylmethyl ether 1
naphthylmethyl ether 1 results in homolytic C–O bond cleavage to give a radical
pair. Recombination of the pair in the solvent cage by bonding between the
naphthylmethyl radical and the ortho position of the aryloxyl radical gives the
cyclohexa-2,4-dienone derivative 2. Free naphthylmethyl and aryloxyl radicals,
formed by escape from the solvent cage, undergo hydrogen abstraction or
dimerization to give products 4–6.
The results of further studies in batch reactors showed that the isolated product 2
does not rearrange to form 3 under either similar photochemical reaction conditions
or dark conditions at 250 °C for 1 h. However, in the presence of catalytic amount
of 2,4,6-trimethylphenol (6), 2 smoothly rearranges to generate 3 under the
photochemical reaction conditions, whereas in the dark, 2 does not react to form 3
even in the presence of 6 [22]. Based on these observations, it appears that the meta-
rearrangement product 3 could be formed by a secondary reaction, in which the
excited state of 2 or 6 promotes an acid-catalyzed Wagner–Meerwein rearrangement
of the ortho-rearrangement product 2 (Scheme 3).
CO2Me
CO2Me
CH2
h
(> 280 nm)
O
O
1
in cage
out of cage
x 2
CO2Me
O
CO2Me
2
H
CO2Me
h
/ 6
5
OH
CO2Me
CO2Me
OH
6
4
3
Scheme 2 Pathways for the formation of products 2–6
123