Facile synthesis of phenacyl iodides from styrenes under visible light irradiation with fluorescent lamps

Article abstract of DOI:10.1016/j.tetlet.2006.12.065

Phenacyl iodides were easily synthesized from styrenes with iodine under irradiation of visible light from a fluorescent lamp.

Full text of DOI:10.1016/j.tetlet.2006.12.065

Tetrahedron Letters 48 (2007) 1131–1133
Facile synthesis of phenacyl iodides from styrenes under
visible light irradiation with fluorescent lamps
Hiroki Nakayama and Akichika Itoh*
Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan
Received 10 November 2006; revised 12 December 2006; accepted 13 December 2006
Available online 8 January 2007
Abstract—Phenacyl iodides were easily synthesized from styrenes with iodine under irradiation of visible light from a fluorescent
lamp.
Ó 2006 Elsevier Ltd. All rights reserved.
Table 1. Study of reaction conditions of synthesis of 4-tert-butyl-
phenacyliodide under irradiation of visible light
a-Halo ketones are important intermediates for many
chemical products, and have attracted a great deal of
interest.1 Among them, phenacyl bromides and chlo-
O
h
ν
rides are commercially available and are the most
widely-used a-halo ketones, while phenacyl iodides have
been scarcely used due to their instability, and the few
synthetic methods available are tedious and use complex
and environmentally high-impact reagents. Thus far, the
methods can be classified into two categories by the
starting material, namely, styrene derivatives2 or aceto-
phenone derivatives.3 Among them, styrene deriva-
tives are, in general, less expensive than acetophenone
derivatives, and are more suitable for large-scale synthe-
sis. With this background in mind, we have engaged in
the development of environmentally benign reactions
under photo-irradiation, and already found that sty-
renes afforded benzoic acids, which were oxidatively
cleaved at the double bond in the presence of a catalytic
amount of iodine and FSM-16, a mesoporous silica, un-
der irradiation of UV.4 In the course of our further
study of these reaction conditions, we also found the
formation of a small amount of phenacyl iodides in
(fluorescent lamp)
I2, additive
R
tBu
O2-balloon
tBu
R = CH2I : 2a
R = OH : 2b
solvent
1 (0.3 mmol)
Entry I2
Additive
(equiv) (mg)
Solvent Time
(h)
Yielda (%)
2a
2b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
0.3
0.3
0.5
1.0
1.0
1.0
1.0
1.0
1.0
0.5
1.0
1.0
1.0
—
1.0
1.0
1.0
1.0
1.0
1.0
1.0
—
—
—
—
EtOAc
EtOAc
EtOAc
EtOAc
MeCN
Acetone 10
iPr2O
10
Hexane 10
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
10
48
10
10
10
30
0
15
46
Trace
0
0
0
0
0
43
50
22
Trace
43
17
64
54
74
Trace
0
FSM-16 (100)
FSM-16 (100)
FSM-16 (100)
FSM-16 (100)
FSM-16 (100)
FSM-16 (100)
FSM-16 (200)
FSM-16 (200)
FSM-16 (200)
FSM-16 (200)
FSM-16 (200)
FSM-16 (300)
10
10
10
10
10
10
24
10
10
10
10
10
10
0
Trace
0
0b
0c
0
0
O
65
71
67
45
30
56
53
Trace
h
ν
0
0
0
0
0
0
I
(fluorescent lamp)
MCM-41 (200) EtOAc
R
I2, FSM-16, O2-balloon
R
H-Y (200)
Na-Y (200)
EtOAc
EtOAc
Scheme 1.
H-ZSM-5 (200) EtOAc
SiO2 (200) EtOAc
a All yields are for pure, isolated products.
b The reaction was carried out in the dark.
c The reaction was carried out under Ar atmosphere.
Keywords: Iodine; Phenacyl iodides; Styrenes; Visible light.
*
Corresponding author. Tel.: +81 58 237 3931x280; fax: +81 58 237
5979; e-mail: itoha@gifu-pu.ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.12.065

1132
H. Nakayama, A. Itoh / Tetrahedron Letters 48 (2007) 1131–1133
some cases. This is the driving force of our further study
on this reaction, and we have successfully found that
phenacyl iodides were selectively obtained under sup-
pression of the formation of benzoic acids under irradi-
ation of VIS from a general-purpose fluorescent lamp.
In this Letter, we report our detailed study of the gener-
ality of synthesis of phenacyl iodides from styrenes
under irradiation of visible light (Scheme 1).
was conducted for a longer reaction time in the presence
of a small amount of iodine (entries 1–4). We were sur-
prised to find that the addition of FSM-166 and MCM-
41,7 mesoporous silicas,8 increased the yield of 2a
(entries 9–11, 16 and 17). Other additives, H-Y,9 Na-Y9
and H-ZSM-5,9 which are typical zeolites, and silica
gel10 were not effective (entries 18–21). Among the sol-
vents examined, ethyl acetate was found to most effi-
ciently afford 2a (entries 5–9). That no oxidation
proceeded or hardly proceeded without either irradia-
tion by a fluorescent lamp or the addition of iodine
shows the necessity of both for this reaction (entries 12
and 14). Furthermore, from the fact that 2a was not
obtained when conducting the reaction under the flow
of argon, we can assume that the actual oxidant in this
reaction is molecular oxygen (entry 13).
Table 1 shows the results of our study of reaction condi-
tions conducted with 4-tert-butylstyrene (1) as a test
substrate under external irradiation by a general-pur-
pose fluorescent lamp in the presence of iodine in an
oxygen atmosphere.5 In general, the yield of 4-tert-
butylphenacyliodide (2a) decreased, and the yield of 4-
tert-butylbenzoic acid (2b) increased when the reaction
Table 2. Synthesis of phenacyl iodides from styrenes under irradiation of visible light
(fluorescent lamp), O2-balloon
h
ν
I2 (1.0 equiv.), FSM-16 (200 mg)
product
substrate
EtOAc, 10 h
Entry
1
Substrate
Product
Yielda (%)
74
COCH2I
1
tBu
2a
tBu
COCH2I
2
3
4
5
73
3
4
COCH2I
68
5
6
COCH2I
38b
72
7
8
COCH2I
9
10
Cl
Cl
COCH2I
6
7
77
46
11
13
O2N
O2N
12
COCH2I
14
8
9
—
—
0
0
15
N
9
16
a All yields are for pure, isolated products.
b 2-Iodo-1-(2-methylphenyl)ethanol (19%) was also obtained.

H. Nakayama, A. Itoh / Tetrahedron Letters 48 (2007) 1131–1133
1133
benzoic acids 21 occurred when the reaction took longer
time. The role of FSM-16 in this reaction is not yet clear;
however, we think that it takes part in acceleration of
both cleavage of iodine to an iodo radical and dehydra-
tion of 19 to afford 20. On the other hand, path (b)
includes the vic-iodohydrin intermediate 22, which is
transformed to 20 by aerobic photo-oxidation at the
benzylic position.
h
ν
I
I2
a
I
I
O2
I
+
R
R
R
17
O
OH
O
O
I
H
R
In conclusion, this new method for the preparation of
phenacyl iodides is convenient in the viewpoint of using
inexpensive styrenes as the starting material and visible
light irradiated from a general-purpose fluorescent
lamp, and is thought to be environmentally benign,
due to all the factors of the use of safe reagents, mole-
cular oxygen as the terminal oxidant, EtOAc of environ-
mentally low impact as solvent, and non-use of metals.
19
18
O
O
[O]
I
OH
R
R
21
20
OH
b
I
H2O
[O]
O2, hν
I2
+
R
R
R
References and notes
22
1. For a recent review, see: Takami, K.; Usugi, S. I.;
Yorimitsu, H.; Oshima, K. Synthesis 2005, 824–839.
2. (a) Evans, R. D.; Schauble, J. H. Synthesis 1986, 727–730;
(b) Cardillo, G.; Shimizu, M. J. Org. Chem. 1977, 42,
4268–4270.
3. (a) Rubottom, G. M.; Mott, R. C. J. Org. Chem. 1979, 44,
1731–1734; (b) Cambie, R. C.; Hayward, R. C.; Jurlina, J.
L.; Ruthledge, P. S.; Woodgate, P. D. J. Chem. Soc.,
Perkin Trans. 1 1978, 126–130.
O
O
I
OH
R
21
20
Scheme 2. Plausible paths for oxidation of styrenes to phenacyl iodide.
4. Itoh, A.; Kodama, T.; Masaki, Y.; Inagaki, S. Synlett
2002, 522–524.
Table 2 shows the scope and limitations of this reaction
using several styrene derivatives. In general, the corre-
sponding phenacyl iodides were afforded in good yields
regardless of an electron-donating group or electron-
withdrawing group at the aromatic nucleus (entries
1–3, 5 and 6).11 Since steric hindrance of the group at
the aromatic nucleus slowed down the reaction rate,
only 38% of 8 and 19% of 2-iodo-1-(2-methylphenyl)eth-
anol were afforded when using 2-methylstyrene (7) as the
substrate. 2-Vinylnaphthalene (13) also reacted in a sim-
ilar manner, and afforded the corresponding iodomethyl
2-naphthyl ketone (14) in a moderate yield (entry 7).
Unfortunately, 2-vinylpyridine (15), which is a hetero-
cyclic compound, gave a complex mixture and the corre-
sponding product was not detected by NMR. On the
other hand, a nonconjugated alkene, 1-dodecene (16),
was intact under this condition (entries 8 and 9).
5. A typical procedure follows: A solution (5 mL) of 4-tert-
butylstyrene (0.3 mmol) and I2 (1 equiv) in dry ethyl
acetate in a Pyrex test tube under aerobic conditions was
stirred and irradiated with four 22-W fluorescent lamps,
which were set up at a distance of 65 mm, for 24 h. The
temperature of the final stage of this reaction was about
50 °C. The reaction mixture was concentrated under
reduced pressure, and the pure product was obtained by
preparative TLC.
6. (a) Inagaki, S.; Koiwai, A.; Suzuki, N.; Fukushima, Y.;
Kuroda, K. Bull. Chem. Soc. Jpn. 1996, 69, 1449–1457; (b)
Inagaki, S.; Fukushima, Y.; Kuroda, K. J. Chem. Soc.,
Chem. Commun. 1993, 680–682.
7. Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J.
C.; Beck, J. S. Nature 1992, 359, 710–712.
8. IUPAC recommends classification of pores to micropore
(D < 2 nm; D, pore diameter) and mesopore (2 nm <
D < 50 nm), see: Everett, D. H. Pure Appl. Chem. 1972,
31, 579–638.
Scheme 2 shows two possible paths of this oxidation,
which are postulated by considering the necessity of
continuous irradiation and molecular oxygen in this
reaction, and the result in the presence of galvinoxyl,
which is a radical trap reagent.12 Path (a) includes radi-
cal species 17, which is thought to be generated by addi-
tion of an iodo radical, formed by irradiation of VIS
from iodine. The radical species traps molecular oxygen
to afford peroxy radical species 18, which subsequently
transforms to phenacyl iodide 20 via hydroperoxide
19. We believe further oxidation to the corresponding
9. H-Y, Na-Y and H-ZSM-5 were purchased from TOSOH
Co.
10. Silica gel (230-400 mesh) was purchased from Merck Co.
11. When using 4-methoxystyrene as the substrate, the prod-
uct was a complex mixture, and the corresponding
carboxylic acid or product of iodination at the aromatic
nucleus was not detected.
12. In the presence of 0.1 equiv of galvinoxyl, 40% of 4-tert-
butylphenacyliodide and 23% of 2-iodo-1-(4-tert-butyl-
phenyl)ethanol were obtained when using 4-tert-butyl-
styrene as the substrate.