Direct addition of supercritical alcohols, acetone or acetonitrile to the alkenes without catalysts

Article abstract of DOI:10.1016/j.tetlet.2007.09.159

The reactions of the alkenes with supercritical organic compounds under non-catalytic conditions were investigated. The H and CR₂OH, CH₂C{double bond, long}OCH₃ or CH₂C{triple bond, long}N of supercritical alcohols (CHR₂OH), acetone (CH₃C{double bond, long}OCH₃) or acetonitrile (CH₃C{triple bond, long}N) added to the C{double bond, long}C bonds of alkenes form C-C bonds between the α-carbons of the supercritical organic compounds and the sp² carbons of the alkenes.

Full text of DOI:10.1016/j.tetlet.2007.09.159

Available online at www.sciencedirect.com
Tetrahedron Letters 48 (2007) 8460–8463
Direct addition of supercritical alcohols, acetone or acetonitrile
to the alkenes without catalysts
a,b,
a
a
a
*
Takashi Kamitanaka,
Tatsuyoshi Hikida, Satoshi Hayashi, Nobuhiro Kishida,
c
a,
*
Tomoko Matsuda and Tadao Harada
a
Department of Materials Chemistry, Ryukoku University, Seta, Otsu, Shiga 520-2194, Japan
Industrial Research Center of Shiga Prefecture, 232 Kamitoyama, Ritto, Shiga 520-3004, Japan
Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan
b
c
Received 1 September 2007; revised 25 September 2007; accepted 27 September 2007
Available online 29 September 2007
Abstract—The reactions of the alkenes with supercritical organic compounds under non-catalytic conditions were investigated. The
H and CR OH, CH C@OCH or CH C„N of supercritical alcohols (CHR OH), acetone (CH C@OCH ) or acetonitrile
2
2
3
2
2
3
3
(
CH C„N) added to the C@C bonds of alkenes form C–C bonds between the a-carbons of the supercritical organic compounds
3
2
and the sp carbons of the alkenes.
Ó 2007 Elsevier Ltd. All rights reserved.
To build carbon skeletons from smaller units, it is
absolutely necessary to form carbon–carbon bonds
between them. Consequently, C–C bond forming reac-
tions are among the most important organic reactions.
and C@O bonds were reduced to the CH–CH and
CH–OH bonds, respectively. When supercritical 2-pro-
panol (critical temperature: T = 508 K, critical pres-
c
sure: P = 4.76 MPa) was used as the reducing reagent,
c
1
Recently, the applications of supercritical fluids were
the reduction of C@O to CH–OH proceeded
9
,10
used for the C–C bond forming reactions. For example,
smoothly,
but the reduction of the C@C bond to
2
3,4
8
the Heck reaction, the Friedel–Crafts reactions, the
the CH–CH bond did not proceed smoothly. One of
the major reactions of the C@C bond with supercritical
alcohol was a C–C bond forming reaction (Scheme 1).
5
6
Cannizzaro-type reaction, and Diels–Alder reaction
were successfully attempted using supercritical water
as the reaction medium without catalysts. The C–C
bond forming reactions in hot water (below the critical
temperature) were also reported. For example, dichloro-
methane converts to glycolic acid via the C–C bond
For example, the H and CH CHOH group of supercrit-
3
ical ethanol (T = 514 K, P = 6.15 MPa) added to the
c
c
C@C bond of styrene to afford its a-hydroxyethylated
derivative, 4-phenyl-2-butanol.
7
forming reaction in hot water. The C–C bond forming
reactions in supercritical or hot water afforded the
expected products in sufficient yields and selectivities.
The use of supercritical fluids for the C–C bond forming
reactions as reaction media or reaction species is a
promising version-up of the reactions from an environ-
mental point of view.
In a previous paper, we reported that the hydroxyalkyl-
ation of the C@C bonds of alkenes or alkynes contain-
ing conjugate phenyl group(s) proceeded more smoothly
than that of the C@C bonds of alkenes containing an
R
We have previously reported the reduction of unsatu-
OH
R
R'
OH
8
–10
rated bonds with supercritical alcohols.
The C@C
R'
supercritical state, 623 K
Keywords: Carbon–carbon bond forming reaction; Supercritical fluid;
Hydroxyalkylation; Acetonylation; Uncatalyzed reaction.
R = H, CH3
R' = H, CH3
*
Corresponding authors. Fax: +81 77 558 1373 (T.K.); fax: +81 77
43 7483 (T.H.); e-mail addresses: kamitanaka.takashi@shiga-irc.-
5
go.jp; harada@rins.ryukoku.ac.jp
Scheme 1. Hydroxyalkylation of styrene with supercritical alcohols.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.159

T. Kamitanaka et al. / Tetrahedron Letters 48 (2007) 8460–8463
8461
unconjugated phenyl group. Herein, we now report the
hydroxyalkylation of the C@C bonds of styrene and
alkenes containing no phenyl group. Moreover, we also
report the C–C bond forming reaction between the C@C
bond and supercritical acetone (T = 508 K, P =
extremely simple. In these reaction systems, ethylben-
zene and toluene were generated. Dehydrogenation of
1
1
methanol to give formaldehyde was also confirmed.
Ether formation between the alcohol molecules is also
1
2
a possible side reaction. However, the concentrations
of these compounds are negligible to that of the hydrox-
yalkylated products.
c
c
4
.70 MPa) or acetonitrile (T = 548 K, P = 4.83 MPa).
c c
The reactions were conducted using glass capillary tubes
0.2 cm inner diameter, 7.0 cm length). The reaction
(
Recently, the rhodium-catalyzed hydroxyalkylation of
the C@C bond with alcohols was reported in which
the styrenes were converted to the corresponding
hydroxyalkyl derivatives with up to approximately
70% yields. In spite of the fairly good yields, this
procedure has the problem of recycling the Rh cata-
lyst. As far as aliphatic alkenes are concerned, one
example is described in the report (2-methylpropene,
yield: 31%).
solutions of the alkenes were loaded into the tubes.
The air in the tube was replaced with argon gas and
the tube was sealed by fusing. The tube was placed in
an autoclave (stainless 316) with methanol that prevents
breaking of the tube due to high pressure during the
reaction. The autoclave was heated by electric furnace
and maintained at 623 K. After 2–20 h, the autoclave
was cooled to quench the reaction. Quantitative analysis
of the products was conducted by GC-FID using the
internal standard method. The products were identified
by the GC-retention times to those of the authentic
samples. Some products were separated by thin layer
1
3
The hydroxyalkylation of the C@C bond with supercrit-
ical alcohol occurs by the fission of a-C–H bond of
supercritical alcohol. We examined the reaction of sty-
rene with supercritical a-deuterio-2-propanol. The yield
of the hydroxyalkyl derivative 3c (entry 4) was much
lower than the yield with the non-deuterated 2-propanol
under the same reaction conditions. This indicates that
the fission of the a-C–H bond of 2-propanol occurs
during the rate determining step.
1
chromatography and identified by the H NMR and
GC–MS.
Table 1 shows the results of the hydroxyalkylation of
styrene and aliphatic alkenes with supercritical alcohols.
As previously reported,8 the hydroxyalkylation of
styrene (1a) with supercritical methanol (T = 513 K,
Next, we attempted the hydroxyalkylation of aliphatic
alkenes to extend the application of this reaction. Two
aliphatic alkenes, 1b and 1c, were employed as the
substrates of the hydroxylalkylation with supercritical
ethanol and 2-propanol at 623 K (entries 5–7). The
yields were much lower than the yield from the hydroxy-
alkylation of styrene (1a) with ethanol or 2-propanol.
c
P = 8.10 MPa), ethanol and 2-propanol proceeded at
c
6
23 K (entries 1–3). Although most of the C–C bond
forming reactions require reagents and/or catalysts to
activate the reaction position of the reagents, this reac-
tion requires no reagents and catalysts other than the
alcohols and the alkenes. Thus, the post-treatment is
a
Table 1. Hydroxyalkylation of C@C bonds using supercritical alcohols under non-catalytic conditions
c
Entry
1
Substrate
Supercritical alcohol
Reaction time (h)
2
Conversion (%)
39
Product
Yield (%)
1a
CH
3
OH 2a
CH OH 2b
3a
3b
6
Ph
Ph
Ph
OH
2
3
1a
1a
CH
3
2
2
2
>99
>99
56
Ph
Ph
OH
OH
(CH
3
3
)
)
2
CHOH 2c
CDOH 2d
3c
3c
70
27
Ph
Ph
4
5
6
7
8
1a
(CH
2
2
20
20
20
20
65
Ph
OH
OH
OH
OH
b
1b
CH
3
CH
2
OH 2b
n.d.
3d
37
12
13
26
5
3
3
7
b
1b
1c
(CH
3
3
)
)
3
CHOH 2c
CHOH 2c
n.d.
3e
3f
5
9
(CH
3
100
100
CF3
OH
1a
CF
3
CH
2
OH 2e
3g
Ph
Ph
a
ꢀ3
Reaction conditions: concentration of alkene in the alcohol at room temperature was 0.10 mol dm , a 0.14-mL portion of the alcoholic solution
was enclosed in the glass tube (inner diameter 2.0 mm, length 70 mm), the reaction temperature was 623 K.
b
c
Conversion could not be determined because the GC-peak of the substrate overlapped with that of the diluent for the GC analysis.
Yields were evaluated by GC (Shimadzu GC-15 A, capillary column DB-17); the yields were calculated based on the alkenes.

8462
T. Kamitanaka et al. / Tetrahedron Letters 48 (2007) 8460–8463
a
Table 2. Direct addition of supercritical acetone and acetonitrile to the alkenes
b
Entry
Substrate
Supercritical fluid
Reaction time (h)
Conversion (%)
91
Product
Yield (%)
Ph
1
1a
(CH
(CH
(CH
3
)
3
)
3
)
2
2
2
C@O 4
C@O 4
C@O 4
2
40
63
49
44
Ph
6a
O
2
3
4
1c
1d
2
2
85
78
97
6
5
6b
6
5
O
6c
O
1a
CH
3
CN 5
10
7
CN
Ph
Ph
a
ꢀ3
Reaction conditions: temperature, 623 K; concentration of alkenes in the solution at room temperature, 0.10 mol dm
.
b
Yields were evaluated by GC (Shimadzu GC-15A, capillary column DB-17); the yields were calculated on the basis of the alkenes.
The compounds possessing CF groups have been a
also be directly added to 1a to afford 7 in 44% yield
(entry 4).
3
2
1
subject of growing interest from both chemical and bio-
logical points of view due to their characteristic chemical
1
4
properties and medicinal uses.
Thus, we carried
In summary, we have developed new C–C bond forming
reactions with alkenes via the fission of the a-C–H bond
of supercritical alcohols, acetone and acetonitrile. Our
results showed that the supercritical fluids can act not
only as unique reaction media, but also as powerful
reagents for organic syntheses. A more detailed and wide-
spread investigation of these reactions is now in progress.
out the reaction of 1a with 2,2,2-trifluoroethanol (2e:
1
5
T = 499 K, P = 4.87 MPa)
to determine if the
c
c
1
,1,1-trifluoro-2-alkanols can be obtained by the reac-
tion of the terminal alkene with 2,2,2-trifluoroethanol.
The reaction was carried out under the same conditions
as the reaction of 1a with 2b. The product 3g possessing
a CF group was obtained in the yield of 26% (entry 8).
3
Generally, the introduction of a CF group into organic
3
1
6
molecules is complicated. For example, 1,1,1-trifluoro-
-alkanols can be prepared in 60–80% overall yield by
the reaction between alkyl magnesium bromide and
References and notes
2
1. (a) Arai, Y.; Sako, T.; Takebayashi, Y. Supercritical
Fluids: Molecular Interactions, Physical Properties, and
New Applications; Springer: Berlin Heidelberg, 2002; (b)
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lithium trifluoroacetate, and the successive NaBH
4
1
7
reduction of the C@O group. The Grignard reaction
and the NaBH reduction are not suitable for a large
4
scale preparation. On the other hand, the hydroxyalkyl-
ation of the C@C bond with supercritical 2,2,2-trifluoro-
ethanol is a promising procedure for the large scale
preparation of 1,1,1-trifluoro-2-alkanols because the
2
3
1
,1,1-trifluoro-2-alkanols can be prepared in one step
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1. Hydrogen gas generation from the alcohols at 623 K was
confirmed by the GC analysis (Shimadzu GC-8A, column:
packed column Shincarbon-T, carrier gas: He 50 mL/min,
detector: TCD). The formaldehyde formation in the
methanol was detected by the Nash’s method. The
18
directly added to alkenes using a silver catalyst or by
photo-irradiation.1 Based on the findings that a super-
critical alcohol can be directly added to the C@C
bond, we expected the direct addition of supercritical
acetone to the C@C bond without a catalyst and by
photo-irradiation. When the alkenes were treated with
supercritical acetone, the alkenes were acetonylated
in moderate yields; that is, C@C + CH C@OCH !
9
9
2
3
3
CH–C–CH COCH . These results are shown in entries
2
3
1
1
1
–3 in Table 2. The alkenes containing no conjugate
phenyl group were more smoothly acetonylated than
styrene. The formations of the aldol products between
the acetone molecules were also confirmed.20 Like the
reaction of styrene with supercritical alcohols or
acetone, acetonitrile under supercritical conditions can

T. Kamitanaka et al. / Tetrahedron Letters 48 (2007) 8460–8463
8463
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phorone (2,6-dimethyl-2,5-heptadiene-4-one) was con-
firmed. They are presumed to be the condensation
products between the acetone molecules.
21. Formation of toluene was confirmed as a by-product in
21% yield. Condensation products of acetonitrile mole-
cules were not detected by the GC analysis.
1
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1