864
Chemistry Letters Vol.33, No.7 (2004)
SN2 Type Hydrolysis of Secondary Alkyl Halides and Sulfonates in Hydrothermal Water
Yuki Yamasaki,ꢀy Takaharu Hirayama, Koichiro Oshima, and Seijiro Matsubaraꢀ
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoutodaigaku-katsura, Nishikyo-ku, Kyoto 615-8510
yDepartment of Industrial Chemistry, Osaka Prefectural College of Technology,
26-12, Saiwai, Neyagawa, Osaka 572-8572
(Received May 10, 2004; CL-040521)
Optically active secondary alkyl halides and sulfonates were
ceeded with inversion of stereochemistry in 81–86%ee. To ex-
amine the effect of leaving group, (S)-2-bromododecane (1b)
and (R)-2-dodecanyl tosylate (1c) were examined for the hydrol-
ysis under hydrothermal condition. As shown in Scheme 1, these
good leaving groups improved the stereospecificity slightly, but
increased the ratio of elimination product 3.
treated with alkaline hydrothermal water at 250 ꢁC in sealed ves-
sel. The hydrolysis mostly proceeded with inversion of stereo-
chemistry.
Hydroxide ion is one of the most common base in chemistry
and also considered to be one of the most gentle nucleophile in
organic synthesis. It is reported, however, that it plays an impor-
tant role as a nucleophile in super critical and hydrothermal wa-
ter.1,2 A loss of hydrogen bond network may increase the nucle-
ophilicity. In addition, these super heated water possesses the
higher dissolving ability of non-polar organic compounds be-
cause of its lower dielectric constant relative to the ambient wa-
ter.3 We have reported hydrolysis of dichloromethane in alkaline
water under hydrothermal condition.1a The nucleophilic attack
of hydroxide ion to the carbon of dichloromethane in SN2 man-
ner was concluded to be the main reaction route. In this commu-
nication, the same condition was applied to the optically active
secondary halide or sulfonate to investigate the stereochemistry
of hydrolysis reaction.
As shown in Table 1, (S)-2-chlorododecane (1a, >98%ee)4
was treated with basic water. A mixture of 1a (2.0 mmol) and ba-
sic water (20 mL) was added in a 30-mL-Teflon vessel which
was placed in stainless autoclave.1a;5;6 The whole was heated
at 250 ꢁC for 2 h. After the whole was cooled to room tempera-
ture, the obtained mixture was extracted with hexane. The com-
bined organic phases were washed with sat. NH4Cl aq and dried
over Na2SO4. After concentration in vacuo, CHBr3 (0.1 mmol)
was added to the concentrated mixture as an internal standard
for 1H NMR analysis in order to determine the product distribu-
tion. The enantiomeric purity of 2 was determined by 19F NMR
analysis after conversion into Mosher’s ester.7
H C
3
n-C
H
H C
n-C H
10 21
10 21
3
0.25 M NaOH
H C
3
+
n-C H
9 19
H O
2
H
OH
Br
H
250 °C, 5 MPa
2 h
1b >98%ee
2
3
3
39% (90%ee)
50%
H C
3
n-C
H
H C
n-C H
10 21
10 21
3
0.25 M NaOH
H C
3
+
n-C H
H O
2
9
19
HO
H
H
OTs
1c >98%ee
250 °C, 5 MPa
2 h
2'
31% (92%ee)
69%
Scheme 1. Effect of leaving group.
The loss of stereospecificity in the hydrolysis reaction of
Table 1 and Scheme 1 implies an existence of SN1 like reaction.
The possibility of racemization that comes from SN2 type reac-
tion by the conjugated base (i.e. Clꢂ, Brꢂ, and TsOꢂ) may be ex-
cluded, because of their low concetration and low nucleophilic-
ity. In these SN1 like reactions, carbocation intermediate even in
a basic condition should contribute the reaction pathway in some
extent. We tried to examine the effect of neighbouring group
which may stabilize the carbocation.8 As shown in Table 2,
(S)-2-phenylpropyl tosylate (4) was treated with basic water un-
der hydrothermal condition. Phenyl group will stabilize carboca-
tion on ꢀ-position through benzenium ion.9 The product of the
hydrolysis reaction was secondary alcohol 5 in 53–56%ee. The
formation of the product was explained as shown in Scheme 2.
In Table 3, results of hydrolysis of (R)-3-phenyl-2-propyl to-
sylate (7) under hydrothermal condition are shown. The hydrol-
ysis product was secondary alcohol 5 with slight stereospecific-
ity. The results can be explained as shown in Scheme 3. A direct
nucleophilic attack gave 5 with inversion stereochemistry, while
the neighbouring phenyl group made a route to the enantiomer
In all cases, hydrolysis reaction competed with elimination
reaction which afforded alkene 3. The hydrolysis reaction pro-
Table 1. Hydrolysis of (S)-2-chlorododecane
H3C
Cl
n-C10H21
H3C
n-C10H21
H3C
Base
H2O
+
Table 2. Hydrolysis of (S)-2-phenylpropyl tosylate
n-C9H19
H
H
OH
250 °C, 5 MPa
H3C
OTs
2 h
1a >98%ee
3
2
H3C
+
H3C
Base
Base
Yield of 2 /%
%ee
Yield of 3 /%
H2O
OH
250 °C, 5 MPa
2.0 M LiOH
2.0 M NaOH
0.25 M NaOH
2.0 M KOH
2.0 M CsOH
25
66
60
40
40
83
86
81
86
83
75
34
34
42
30
4
5
6
2 h
Base
Yield of 5 /%
%ee
Yield of 6 /%
0.2 M NaOH
0.2 M CsOH
63
61
56
53
30
35
Copyright Ó 2004 The Chemical Society of Japan