Oxidative transformation of arylmethyl bromides and alcohols with a combination of mesoporous silica FSM-16 and alkali iodides under photoirradiation

Article abstract of DOI:10.1021/ol016210d

(Equations presented) A mesoporous silica FSM-16 was found to be a selective and recyclable promoter for the oxidative dehalogenation of arylmethyl bromides to provide the corresponding alcohols and for the oxidation of arylmethyl alcohols to provide the corresponding aldehydes with a combination of alkali iodides and solvents under photoirradiation conditions.

Full text of DOI:10.1021/ol016210d

ORGANIC
LETTERS
2
001
Vol. 3, No. 17
653-2656
Oxidative Transformation of Arylmethyl
Bromides and Alcohols with a
Combination of Mesoporous Silica
FSM-16 and Alkali Iodides under
Photoirradiation
2
,†
†
‡
†
Akichika Itoh,* Tomohiro Kodama, Shinji Inagaki, and Yukio Masaki
Gifu Pharmaceutical UniVersity, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan, and
Toyota Central R & D labs., Inc., Aichi, 480-1192, Japan
itoha@gifu-pu.ac.jp
Received May 31, 2001
ABSTRACT
A mesoporous silica FSM-16 was found to be a selective and recyclable promoter for the oxidative dehalogenation of arylmethyl bromides to
provide the corresponding alcohols and for the oxidation of arylmethyl alcohols to provide the corresponding aldehydes with a combination
of alkali iodides and solvents under photoirradiation conditions.
6
In our studies on the utilization of mesoporous silicas in
presence of NaI in acetone and oxidation of 2 to 4-tert-
1
organic synthesis, we have found that R-hydroxycarboxylic
2
butylbenzaldehyde (3) in the presence of CsI in iPr O were
observed under photoirradiation (Scheme 1).
2
acids, phenyl acetic acid derivatives, and N-protected
3
R-amino acids afforded the carbonyl compounds through
an oxidative decarboxylation reaction in the presence of a
4
mesoporous silica, FSM-16, under photoirradiation. Fur-
Scheme 1
thermore, arylmethyl bromides, which have no carboxyl
group, were found to give the corresponding aromatic
carboxylic acids in one step with FSM-16 under photoirra-
5
diation. In the course of investigation of this reaction, we
found FSM-16 to show new promoting effects in the presence
of alkali iodides: exclusive transformation of 4-tert-butyl-
benzyl bromide (1) to 4-tert-butylbenzyl alcohol (2) in the
†
Gifu Pharmaceutical University.
Toyota Central R & D labs., Inc.
‡
Although the transformation of arylmethyl halides to the
corresponding alcohols and the oxidation of arylmethyl
alcohols to the corresponding aldehydes had been developed
by many workers over many years, these methods are
sometimes problematic because drastic conditions or envi-
ronmentally detrimental heavy metals are required.
(
1) Itoh, A.; Kodama, T.; Maeda, S.; Masaki, Y. Tetrahedron Lett. 1998,
9, 9461. Itoh, A.; Kodama, T.; Masaki, Y. Synlett 1999, 357.
2) Itoh, A.; Kodama, T.; Inagaki, S.; Masaki, Y. Org. Lett. 2000, 2,
31.
3
(
7
3
(
(
3) Itoh, A.; Kodama, T.; Inagaki, S.; Masaki, Y. Chem. Lett. 2000, 542.
4) Inagaki, S.; Koiwai, A.; Suzuki, N.; Fukushima, Y.; Kuroda, K. Bull.
Chem. Soc. Jpn. 1996, 69, 1449. Inagaki, S.; Fukushima, Y.; Kuroda, K. J.
Chem. Soc., Chem. Commun. 1993, 680.
On the other hand, our reaction is thought to be useful
(5) Itoh, A.; Kodama, T.; Inagaki, S.; Masaki, Y. Org. Lett. 2000, 2,
8
2
455.
and complementary to other methods, since it is mild and
1
0.1021/ol016210d CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/27/2001

does not require the use of environmentally detrimental
reagents. We now report our study on the generality of these
oxidative transformations with FSM-16 in the presence of
alkali iodides under photoirradiation.
Table 1 shows the results of the transformation of 4-tert-
butylbenzyl bromide (1, 50 mg) in the presence of silica (100
mg) and alkali iodide in several solvents using 400-W high-
to be suitable for the reaction to afford 2 in 94% yield with
FSM-16 (entries 1-7). In the dark, only the starting
material was recovered even in the presence of FSM-16
1
0
(entry 8). Under N
10% of 2 was obtained even in the presence of 1 mol of
O (entries 9 and 10). These results show that the oxygen
2
, 12% of 2 was obtained, and also only
H
2
in air is crucial for this reaction. Among alkali iodides
examined, NaI was found to be superior to other iodides to
afford 2 in high yield (entries 7, 11-13). Furthermore, more
than 1 mole equiv of NaI was required to complete the
reaction in 24 h, and a large amount of the starting material
was recovered when 0.5 equiv of NaI was used (entries 7,
Table 1. Study of Reaction Conditions for Transformation of
Arylmethyl Bromides to Alcohols with FSM-16
1
4, 15). The reason for the difference in the effect between
NaI and other iodides is not yet clear, but the solubility in
acetone, the size, and the dissociation energy of alkali
1
1
iodides are assumed to play an important role in this
1
2
13
reaction. Other mesoporous silicas, MCM-41, HMS, and
recovery
MI (equiv) of 1 (%)a of 2 (%)
yield
1
4
entry solvent
silica
10%Ti-HMS, were found to give 2 in yields somewhat
lower than that obtained with FSM-16 (entries 16-18). Only
22% yield of 2 was obtained without FSM-16 under
photoirradiation (entry 19).
Table 2 shows the results for transformation of several
arylmethyl halides to the corresponding alcohols. Neither an
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
hexane FMS-16
toluene FMS-16
NaI (1.2)
NaI (1.2)
NaI (1.2)
NaI (1.2)
NaI (1.2)
NaI (1.2)
NaI (1.2)
NaI (1.2)
NaI (1.2)
NaI (1.2)
LiI (1.2)
KI (1.2)
CsI (1.2)
NaI (0.5)
NaI (2.0)
NaI (1.2)
NaI (1.2)
NaI (1.2)
NaI (1.2)
3
30b
27c
18d
15e
5
0
94
0f
12g
10h,i
72
78
71
61j
91
67
79
77
22
38
65
52
92
87
trace
quant
90
86
26
3
MeCN
AcOEt
Et2O
FMS-16
FMS-16
FMS-16
CH2Cl2 FMS-16
acetone FMS-16
acetone FMS-16
acetone FMS-16
acetone FMS-16
acetone FMS-16
acetone FMS-16
acetone FMS-16
acetone FMS-16
acetone FMS-16
acetone MCM-41
acetone HMS
Table 2. Transformation of Arylmethyl Bromides to Alcohols
with FSM-16/NaI/hν
1
1
1
1
1
1
1
1
1
1
8
23
trace
17
2
11
35
acetone 10% Ti-HMS
acetone
a
The yield included a small amount of unidentified products, which were
b
c
inseparable from 1. Also, 52% of 3 was obtained. Also, 36% of 3 was
obtained. Also, 14% of 3 was obtained. Also, 15% of 3 was obtained.
The reaction was carried out in the dark. The reaction was carried out
under N2 atmosphere. The reaction was carried out in the presence of 1
d
e
f
g
h
i
j
equiv of H2O under N2. Also, 2% of 3 was obtained. Also, 8% of 3 was
obtained.
pressure mercury lamps under an aerobic atmosphere at room
9
temperature. Among the solvents used, acetone was found
(6) Photolysis of benzyl halides has been reported by several groups:
Alvaro, M.; Corma, A.; Garcia, H.; Miranda, M. A.; Primo, J. J. Chem.
Soc., Chem. Commun. 1993, 1041. Fukuzumi, S.; Hironaka, K.; Tanaka,
T. J. Am. Chem. Soc. 1983, 105, 4722. Gardini, G. P.; Charlton, J. L.;
Bargon, J. Tetrahedron Lett. 1982, 23, 987. Appleton, D. C.; Brocklehurst,
B.; McKenna, J.; McKenna, J. M.; Thackeray, S.; Walley, A. R. J. Chem.
Soc., Perkin Trans. 2 1980, 87. Katritzky, A. R.; Cook, M. J.; Brown, S.
B.; Cruz, R.; Millet, G. H.; Anani, A. J. Chem. Soc., Perkin Trans. 1 1979,
electron-withdrawing nor -donating group such as 4-nitro (4)
and 4-methoxy group (6) as an aromatic substituent exerted
2
493. Katritzky, A. R.; Brown, S. B. Synthesis 1978, 619. Appleton, D. C.;
Brocklehurst, B.; McKenna, J.; McKenna, J. M.; Smith, M. J.; Taylor, P.
S.; Thackeray, S.; Walley, A. R. J. Chem. Soc., Chem. Commun. 1977,
(9) Typical Procedure. In a Pyrex tube, a suspension of 4-tert-
butylbenzyl bromide (1, 50 mg), silica (100 mg), and NaI (39.6 mg, 1.2
equiv) in dry acetone (5 mL) was stirred and irradiated externally at room
temperature with a 400-W high-pressure mercury lamp under an aerobic
atmosphere for 24 h. FSM-16 was then filtered off and washed with ethyl
acetate, and the filtrate was washed with aqueous sodium thiosulfate solution
and brine. The organic layer was dried over magnesium sulfate and
concentrated under reduced pressure. Pure 4-tert-butylbenzyl alcohol (2)
(33.9 mg, 94%) was obtained after purification by preparative TLC.
1
08.
7) ComprehensiVe Organic Transformations: A Guide to Functional
Group Preparations; Larock, R. C. Ed.; Wiley-VCH: New York, 1989.
8) We have already discovered that arylmethyl alcohols and allylic
(
(
alcohols provided the corresponding aldehydes or ketones with iodine under
photoirradiation conditions; however, the method using CsI instead of iodine
is more facile since CsI is easier to handle than iodine: Itoh, A.; Kodama,
T.; Masaki, Y. Chem. Lett., in press.
2654
Org. Lett., Vol. 3, No. 17, 2001

any negative influence on the reaction (entries 1 and 2). The
base-sensitive ester moiety of methyl 4-(bromomethyl)-
benzoate (8) remained intact under the reaction conditions,
and the corresponding alcohol 9 was obtained in high yield
2
examined, iPr O was found to afford the best results and to
17
give 16 in 87% yield (entries 1-10). Although a stoichio-
metric amount of CsI was required to give 16 in high yield,
an excess amount of CsI retarded the oxidation (entries 11
and 12). On the other hand, the result that, without irradiation,
oxygen, FSM-16 or alkali iodide, 16 was not obtained or
obtained only in low yield shows the necessity of all of the
foregoing factors for this reaction (entries 13-17). NaI and
KI were also found to promote this oxidation; however, the
yield of 16 was lower than that with CsI (entries 18 and
(
entry 3).15 R-Methylbenzyl bromide (10), a secondary
bromide, also afforded R-methylbenzyl alcohol (11) in the
same manner as 1 (entry 4). Furthermore, cinnamyl bromide
(12), which possesses a double bond conjugated with the
aromatic nucleus, afforded cinnamyl alcohol (13) in high
yield (entry 5). n-Hexadecyl bromide (14), a simple alkyl
halide, was intact even after 48 h under the same reaction
conditions (entry 6).
1
2
19). The results with other mesoporous silicas, MCM-41,
1
3
14
HMS, and 10% Ti-HMS, showed FSM-16 to be better
as a promoter of the oxidation (entries 20-22).
Table 3 shows the results of photooxidation of benzhydrol
(15) to benzophenone (16), the second step in Scheme 1, in
Other primary arylmethyl alcohols and allylic alcohols
exclusively afforded the corresponding aldehydes (Table 4).
Table 3. Study of Reaction Conditions for Transformation of
Arylmethyl Alcohols to Aldehydes with FSM-16
Table 4. Transformation of Arylmethyl Alcohols to Aldehydes
with FSM-16/CsI/hν
recovery
yield
entry solvent
Et2O
silica
MI (equiv) of 15 (%) of 16 (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
FMS-16
CsI (1.0)
CsI (1.0)
CsI (1.0)
CsI (1.0)
CsI (1.0)
CsI (1.0)
CsI (1.0)
CsI (1.0)
CsI (1.0)
CsI (1.0)
CsI (0.5)
CsI (2.0)
CsI (1.0)
CsI (1.0)
CsI (1.0)
16
97
29
88
91
90
19
97
0
61
2
68
6
1
0
72
0
64
87
17
26
0a
0b
14
acetone FMS-16
hexane FMS-16
MeOH
THF
DMF
benzene FMS-16
FMS-16
FMS-16
FMS-16
MeCN
H2O
FMS-16
FMS-16
FMS-16
FMS-16
FMS-16
FMS-16
FMS-16
1
1
1
1
1
1
1
1
1
1
2
2
2
iPr2O
iPr2O
iPr2O
iPr2O
iPr2O
iPr2O
iPr2O
iPr2O
iPr2O
iPr2O
iPr2O
iPr2O
iPr2O
0
34
39
99
91
c
FMS-16
c
c
50
14
57
85
56
78
85
FMS-16
FMS-16
MCM-41
HMS
NaI (1.0)
KI (1.0)
CsI (1.0)
CsI (1.0)
34
trace
34
8
a
Also, 18% of 18 was recovered. b Also, 42% of 22 was recovered.
c
Also, 86% of 24 was recovered.
10% Ti-HMS CsI (1.0)
trace
a
b
The reaction was carried out in the dark. The reaction was carried
c
out under a flow of argon. Not negligible amount of 15 was recovered
with inseparable byproducts.
Cinnamyl alcohol (13) was oxidized to cinnamaldehyde (17)
in high yield (81%) in the presence of FSM-16 and 1 equiv
of CsI (entry 1). 4-tert-Butylbenzyl alcohol (2) was less
reactive than 13; however, 3 was obtained in 55% yield after
the presence of FSM-16 and alkali iodide in several solvents
using 400-W high-pressure mercury lamps at room temper-
ature under an aerobic atmosphere.16 Among the solvents
24 h (entry 2). Both trans-2-decen-1-ol (18) and phytol (20),
(
14) Zhang, W.; Froba, M.; Wang, J.; Tanev, P. T.; Wong, J.; Pinnavaia,
(
10) FSM-16 used in this study was synthesized according to ref 4. The
T. J. J. Am Chem. Soc. 1996, 118, 9164. Tanev, P. T.; Chibwe, M.;
Pinnavaia, T. J. Nature 1994, 368, 321.
(15) Since a commonly used method for the transformation of arylmethyl
halides to the corresponding alcohols includes the nucleophilic displacement
of halogen by a hydroxide ion in basic aqueous solution, our method is
mild and complementary to other methods and is thought to be useful for
base-sensitive substrates; see ref 7.
unit cell dimension of this FSM-16 was 4.63 nm. The pore diameter was
.9 nm, and the specific surface area was 882 m /g.
(
(
2
2
11) Su, T.-M R.; Riley, S. J. J. Chem. Phys. 1979, 71, 3194.
12) Kresge, C. T.; Leonowicz, M. E.: Roth, W. J.; Vartuli, J. C.; Beck,
J. S. Nature 1992, 359, 710.
13) Tanev, P. T.; Pinnavaia, T. J. Science 1995, 267, 865.
(
Org. Lett., Vol. 3, No. 17, 2001
2655

which are allylic alcohols, were found to afford the corre-
sponding aldehydes 19 and 21 in moderate yield (entries 3
and 4). In all the cases mentioned above, the corresponding
carboxylic acids could not be detected. Furthermore, isoch-
romanone (23) was directly obtained from isochroman (22)
in 31% yield (entry 5). Unfortunately, 4-tert-butylcyclohexyl
alcohol (24), which is a simple alkanol, remained intact under
the conditions, and only the starting material was recovered
even after 48 h (entry 6).
The promoter FSM-16 was found to be a recyclable
photocatalyst for both steps. Thus, the recovered FSM-16,
which was washed with distilled water to remove alkali
iodides and dried at room temperature for 2 h under reduced
pressure, showed no loss of activity for the reaction after
being used three times (Table 5).
of NaI. Furthermore, aldehyde 3, which is a possible
intermediate from 1 under the conditions without NaI, was
5
recovered intact. Since the arylmethyl bromides generally
afforded the corresponding aldehyde and carboxylic acid
5
without NaI, the iodide anion must inhibit the oxidation steps
from alcohol to aldehyde and/or carboxylic acid. We believe
a benzyl radical species, generated from the bromides under
18
photoirradiation, participates in the course of this reaction.
In the second step, oxidation of the alcohols, iodine was
thought to be generated from CsI in situ as judged by the
color of the reaction mixture, which changes from colorless
to dark brown. As shown in Scheme 2, an iodo radical, which
Scheme 2
Table 5. Recycle of FSM-16
yield of product (%)
1
st
2nd
3rd
cycle
cycle
cycle
FSM-16, NaI, hν
9
8
1
6
85
86
1
1
8 2
acetone, rt, 24 h
FSM-16, CsI, hν
iPr2O, rt, 24 h
86
83
5
8 16
is generated under the photoirradiation conditions, abstracts
the hydrogen atom at the benzylic position of the starting
material. The resulting radical species 25 reacts with
Although the mechanism of this series of transformations,
including the solvent effect and which steps are promoted
by FSM-16, is not clear, oxygen in air has an important role.
It is required for these reactions to proceed smoothly, since
the yield of the product for each step was reduced under a
flow of nitrogen or argon. In regard to the first step,
formation of the alcohol, several intermediates can be
considered. In nucleophilic substitution reactions of alkyl
bromides or alkyl chlorides, NaI is sometimes used as a
promoter that generates the corresponding iodide in situ.
19
molecular oxygen to generate the peroxy radical species 26,
which produces 27 and 25 through an autoxidation path. The
hydroperoxide 27 is thought to be reduced by hydrogen
iodide that is generated in situ, to the corresponding carbonyl
20
product. We have not obtained any direct evidence for the
intermediates in this path, and a more detailed study is now
21
in progress in our laboratory.
In conclusion, this new method for the transformation of
arylmethyl bromides to the corresponding aldehydes via
arylmethyl alcohols is thought to be convenient in view of
the weak acidic conditions, the use of a recyclable solid
catalyst, and the non-requirement of environmentally detri-
4-tert-Butylbenzyl iodide, however, afforded the correspond-
ing alcohols 2 only in 18% yield under the conditions without
NaI, although 92% yield of 2 was obtained in the presence
(
16) Typical Procedure. In a Pyrex tube, a suspension of benzhydrol
mental heavy metals such as MnO
2
.
(
14, 50 mg), FSM-16 (100 mg), and CsI (70.5 mg, 1 equiv) in dry iPr2O (5
mL) was stirred and irradiated externally at room temperature with a 400-W
high-pressure mercury lamp under an aerobic atmosphere for 24 h. FSM-
OL016210D
1
6 was then filtered off and washed with ethyl ether and distilled water.
The filtrate was washed with aqueous sodium thiosulfate solution and brine.
The organic layer was dried over sodium sulfate and concentrated under
reduced pressure. Pure benzophenone (15) (43.1 mg, 87%) was obtained
after purification by preparative TLC.
(18) Kerr, J. A. Chem. ReV. 1966, 66, 465.
(19) Mallory, F. B.; Mallory, C. W. Org. React. 1984, 30, 1.
(20) We believe that iodine is reproduced in situ, since the dark brown
color of the reaction mixture seemed to remain unchanged as such.
(21) Participation of the peroxide species from iPr2O, which may be
generated by oxygen and photoirradiation, cannot be ruled out since the
reaction also proceeded without CsI (entry 16 in Table 3).
(17) Unfortunately, direct transformation from 1 to 3 under the same
condition was not successful: only 15% of 3 and 11% of 2 were obtained
with 49% recovery of 1.
2656
Org. Lett., Vol. 3, No. 17, 2001