Exalted resonance demands in the substituent effects on the acetolyses of 2-arylethyl trifluoromethanesulfonates destabilized by cn and cf3 groups

Article abstract of DOI:10.1246/bcsj.82.254

Substituent effects on the acetolysis rates of 2-aryl-l-cyano-l- (trifluoromethyl)ethyl trifluoromethanesulfonates (α-OTf) and 2-aryl-2-cyano-2-(trifluoromethyl)ethyl trifluoromethanesulfonates (ss-OTf) were investigated by using LArSR equation. The obtained p and r⁺ values were p = -3.28, r⁺ = 0.98 and p = -3.48,r⁺ = 0.93 for the acetolysis of α-OTf and ss-OΥi, respectively. The obtained p values are comparable to those for typical aryl-assisted solvolyses, but the r⁺ values are much larger. The large r+ values suggest that the ester bond cleavages in the deactivated aryl-assisted solvolyses are assisted by the strong participation of the ss-aryl group.

Full text of DOI:10.1246/bcsj.82.254

254
Bull. Chem. Soc. Jpn. Vol. 82, No. 2, 254–260 (2009)
© 2009 The Chemical Society of Japan
Exalted Resonance Demands in the Substituent Effects on the
Acetolyses of 2-Arylethyl Trifluoromethanesulfonates
Destabilized by CN and CF3 Groups
Satoshi Usui,*1,2 Shoko Tsuboya,2 Yukihiro Umezawa,2 Ken Hazama,2 and Mutsuo Okamura2
1Department of Environmental Science, Faculty of Science, Niigata University, 8050 Ikarashi-2, Niigata 950-2181
2Graduate School of Science and Technology, Niigata University, 8050 Ikarashi-2, Niigata 950-2181
Received September 2, 2008; E-mail: usui@env.sc.niigata-u.ac.jp
Substituent effects on the acetolysis rates of 2-aryl-1-cyano-1-(trifluoromethyl)ethyl trifluoromethanesulfonates
(¡-OTf) and 2-aryl-2-cyano-2-(trifluoromethyl)ethyl trifluoromethanesulfonates (¢-OTf) were investigated by using
LArSR equation. The obtained µ and r+ values were µ = Õ3.28, r+ = 0.98 and µ = Õ3.48, r+ = 0.93 for the acetolysis
of ¡-OTf and ¢-OTf, respectively. The obtained µ values are comparable to those for typical aryl-assisted solvolyses, but
the r+ values are much larger. The large r+ values suggest that the ester bond cleavages in the deactivated aryl-assisted
solvolyses are assisted by the strong participation of the ¢-aryl group.
Solvolyses of substrates bearing a strong electron-with-
is extremely destabilized by the two electron-withdrawing
groups attached to the reaction center is of interest. From this
perspective, the substituent effect on the acetolysis rates of
2-aryl-1-cyano-1-(trifluoromethyl)ethyl trifluoromethanesulfo-
nates (abbreviated as ¡-OTf) was investigated by using LArSR
equation, and the transition-state structure is discussed on the
basis of its µ and r+ values.
drawing substituent at the reaction center have been attracting
great amount of interest in the area of physical organic
chemistry.1 The investigations have mostly focused on the
structure and reactivity of such a destabilized transition state or
carbocation intermediate, which will provide fundamental
insights into the carbocation chemistry. For this purpose,
CF3, CN, and carbonyl groups have been adopted for the
electron-withdrawing groups.
Results and Discussion
A wide variety of 2-arylalkyl substrates are known to
undergo aryl-assisted solvolyses2,3 (kÅ mechanism) in which
the cleavage of the bond between the reaction center and
the leaving group (CÍL) is driven by the participation of
neighboring aromatic ³-electrons. Because of the direct
interaction between the aryl ³-electrons and the ·*-orbital of
the CÍL bond, the structure and stability of the transition state
are significantly affected by the substituent at the aromatic ring.
Such perturbation of the substituent enables us to investigate
the transition-state structure in terms of substituent effect on
solvolysis rates.
When ¡-OTf was solvolyzed in acetic acid, 19F NMR and
1H NMR spectra of the sample solution exhibited changes
according to substrate consumption and product formations, as
shown in Figures 1 and 2 for the acetolysis of the p-Me-
substituted derivative. In Figure 1, 19F NMR signals at Õ75.3
and Õ77.7 ppm, which are assigned to two CF3 groups in
¡-OTf, decayed via 1st-order kinetics, and signals at Õ65.2,
Õ71.5, and Õ80.0 ppm were observed at the end of the
acetolysis. The 19F NMR signal at Õ80.0 ppm is reasonably
ascribed to trifluoromethanesulfonic acid (abbreviated as
TfOH) by comparison with that of the authentic sample. The
solvolysis product exhibiting a 19F NMR signal at Õ71.5 ppm
was identified as 2-aryl-2-cyano-2-(trifluoromethyl)ethyl ace-
tate (abbreviated as ¢-OAc) which exhibits an AB quartet
1H NMR signal of the CH2 group at 4.86 ppm as shown in
Figure 2. The other product with a Õ65.2 ppm 19F NMR signal
The effects of aryl substituents on reaction rates have been
examined extensively by using LArSR equation,4
o
þ
ꢁ þ
log k=kH ¼ µð· þ r ꢀ·R Þ
ð1Þ
where resonance demand, denoted as r+, represents a measure
of the delocalization of the positive charge in the transition
state over the aromatic ³-orbital. For the substituent effects on
the rates of aryl-assisted solvolyses, moderate r+ values of
around 0.5, which systematically vary with substrate structure,
have been obtained. The variation is interpreted as the change
in the degree of phenyl participation in the transition state.5,6
Thus, the substituent effect on the solvolysis rates of 2-
arylalkyl substrates would be a good criterion for evaluating
the effect of the ¡-electron-withdrawing group on the tran-
sition-state structure. In this paper, 2-arylethyl solvolysis which
1
exhibited a singlet H NMR signal at 7.80 ppm and is ascribed
to 3-aryl-2-(trifluoromethyl)acrylonitrile (abbreviated as Sty).
In addition to these final products, an intermediate product,
which exhibits 19F NMR signals at Õ70.8 and Õ75.9 ppm, was
accumulated and diminished with the progress of the acetol-
ysis. This intermediate product exhibits an AB quartet 1H NMR
signal at 5.18 ppm and was identified as 2-aryl-2-cyano-2-
(trifluoromethyl)ethyl trifluoromethanesulfonate (abbreviated
as ¢-OTf).
The formation of ¢-OTf during the acetolysis is indicative of
Published on the web February 13, 2009; doi:10.1246/bcsj.82.254

S. Usui et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 2 (2009)
255
CN
CN
CF3C6H5
CF3
TfOH
CN
CF3
CN
CF3
CF3 AcO
TfO
OTf
200 min
130 min
60 min
0 min
Figure 1. 19F NMR spectra for the acetolysis of ¡-OTf at 130 °C.
CN
CF3
CN
CN
CF3
CN
CF3
CF3
TfO
AcO
OTf
200 min
130 min
60 min
0 min
Figure 2. 1H NMR spectra for the acetolysis of ¡-OTf at 130 °C.
the intervention of a non-classical phenonium (=spiro[2,5]-
octadienylium) ion intermediate7 which affords ¢-OTf and ¢-
OAc by the nucleophilic addition of the trifluoromethanesul-
fonate anion and acetic acid, respectively. Hence, the acetolysis
of ¡-OTf is suggested to proceed through rate-limiting
phenonium ion formation followed by partitioning between
the ¢-OAc and ¢-OTf formations as has been shown for the
solvolysis of 2-phenylpropyl brosylate (=p-bromobenzenesul-
fonate).2b The rate of ¢-OTf formation is then expressed in
terms of the rate of phenonium ion formation, kš, and the
partitioning factor between the ¢-OAc and ¢-OTf formations,
F. Acetolysis of ¢-OTf is supposed to afford ¢-OAc as a sole
product, since ¢-OAc was the only nucleophilic substitution
product throughout the acetolysis. This assumption is also
supported by the fact that the formation of ¢-OAc, shown in
Figure 3, did not obey 1st-order kinetics, but the sum of ¢-OAc
and ¢-OTf did. As an analogy to the acetolysis of ¡-OTf, the
acetolysis of ¢-OTf is also expected to proceeds through the

256
Bull. Chem. Soc. Jpn. Vol. 82, No. 2 (2009)
Destabilized Acetolysis of 2-Arylethyl System
1.0
Table 1. Reaction Rate Constants and Partitioning Factors
for the Acetolyses of ¡-OTf at 130 °C
0.8
Substituent
kÅ¡/10Õ5 sÕ1
F
kE/10Õ5 sÕ1 k¢/10Õ5 sÕ1
p-MeO
p-MeS
p-MeO-m-Cl
3,4-Me2
p-Me
3,5-Me2
m-Me
H
251
114
0.67
0.69
0.66
0.54
0.57
0.35
0.37
0.32
293
79.5
44.0
32.9
13.5
4.02
1.62
0.783
0.6
0.4
0.2
22.7
20.3
9.23
3.48
1.65
0.668
1.82
2.14
2.08
1.93
1.75
1.94
0
0
50
100
150
200
250
300
d½¢-OAcꢀ
Time / min
¼ Fkꢀ¡½¡-OTfꢀ þ k¢½¢-OTfꢀ
ð5Þ
dt
Figure 3. Time profiles of the substrate and product
fractions for the acetolysis of ¡-OTf at 130 °C; closed
circle, ¡-OTf; open circle, TfOH; closed triangle, ¢-OAc;
closed square, ¢-OTf; open square, Sty.
By resolving these differential equations, the concentration of
the substrate and the products are obtained as a function of
time, as follows;
½¡-OTfꢀ ¼ ½¡-OTfꢀ0 expðꢁðkꢀ¡ þ kEÞtÞ
ð6Þ
ð1 ꢁ FÞkꢀ¡
kE
½¢-OTfꢀ ¼ ½¡-OTfꢀ
0 k¢ ꢁ kꢀ¡ ꢁ kE
CN
CF3
CN
ꢂ fexpðꢁðkꢀ¡ þ kEÞtÞ ꢁ expðꢁk¢tÞg
ð7Þ
ð8Þ
OTf
CF3
Sty
α-OTf
k∆α
kE
½Styꢀ ¼ ½¡-OTfꢀ0
expðꢁðkꢀ¡ þ kEÞtÞ
kꢀ¡ þ kE
½¢-OAcꢀ ¼ ½¡-OTfꢀ0 ꢁ ½¡-OTfꢀ ꢁ ½¢-OTfꢀ ꢁ ½Styꢀ ð9Þ
+
where [¡-OTf]0 represents the concentration of ¡-OTf at t = 0.
The reaction rate constants and F value were determined by the
least-squares curve fitting8 of the substrate and the product
fractions obtained from the 19F NMR signal integrals to eqs 6
to 9. The solid lines in Figure 3 indicate the substrate and
product fractions calculated by the above equations with the
thus-obtained kÅ¡, k¢, kE, and F values for the acetolysis of
¡-OTf with the p-Me substituent.
CN
CF3
(1-F)
F
-OTf
AcOH
kβ
CN
CF3
CN
TfO
β-OTf
AcO
CF3
β-OAc
Acetolyses of ¡-OTf with a series of aryl substituents
exhibited similar solvolysis products and time dependencies of
the substrate and products fractions, except for the p-MeO
and p-MeS derivatives which gave no elimination products.
Although competition of discrete kÅ and ks mechanisms and
changes in their rate ratio with aryl substituents have been
shown for many ¢-arylalkyl solvolyses,3 no 2-aryl-1-cyano-1-
(trifluoromethyl)ethyl acetate which would be obtained by
ks mechanism, was observed in the present acetolysis. This
observation indicates that the acetolysis mechanism proposed
in Scheme 1 is constant and the procedure for obtaining the
reaction rate constants and F value described above is valid for
all ¡-OTf derivatives studied here. The obtained reaction rate
constants and F values are summarized in Table 1.
It is obvious from Table 1 that kE are nearly constant, while
kÅ¡ and k¢ varied by a factor of about 400 with the change of
substituent from H to p-MeO. The small substituent effect on kE
indicates that the elimination reaction proceeds by the E2
mechanism rather than by E1, since the E1 mechanism should
involve a rate-determining phenonium ion formation so that it
Scheme 1.
phenonium ion, however, a solvent-assisted SN2 displacement
reaction (ks mechanism) cannot be excluded from the acetolysis
mechanism of ¢-OTf. The detailed mechanism will be dis-
cussed below based on the substituent effect on the acetolysis
rates of ¢-OTf, k¢. As for the elimination product, time
dependency of its formation obeyed 1st-order kinetics from the
beginning to the end of the acetolysis, indicating that this
product is directly obtained by the acetolysis of ¡-OTf.
According to these observations, a summary of the acetolysis
mechanism of ¡-OTf is depicted in Scheme 1.
The reaction rate constants and F value described in
Scheme 1 were obtained by the following procedure. Based
on Scheme 1, the rate equations for the substrate and products
are as follows:
d½¡-OTfꢀ
¼ ꢁðkꢀ¡ þ kEÞ½¡-OTfꢀ
ð2Þ
ð3Þ
ð4Þ
dt
d½¢-OTfꢀ
¼ ð1 ꢁ FÞkꢀ¡½¡-OTfꢀ ꢁ k¢½¢-OTfꢀ
would result in a similar substituent effect as that for kš
.
dt
Therefore, kE values of around 2.0 © 10Õ5 sÕ1 are also expected
for the acetolyses of p-MeO and p-MeS derivatives. Thus, the
absence of Sty in the acetolyses of these electron-releasing
d½Styꢀ
¼ kE½¡-OTfꢀ
dt

S. Usui et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 2 (2009)
257
3
ought to be stabilized by the delocalization over the aromatic
³-orbital. This variation in r+ values is shown for benzylic SN1
solvolyses with a series of electron-withdrawing substituents at
the reaction center,11 where an increase of the r+ value by a
factor of 1.4 has been observed by the substitution of the ¡-Me
group with a CF3 group in the t-cumyl solvolysis.
p
-MeO
p
-MeS
In the acetolysis of ¡-OTf, it may be plausible that the two
electron-withdrawing CN and CF3 groups strongly destabilize
the positive charge in the aryl-assisted transition state, forcing a
large positive charge to be delocalized over the aromatic ³-
orbital. However, the acetolysis of ¡-OTf exhibited essentially
the same µ value as those for the aryl-assisted 2-arylalkyl
acetolyses without an electron-withdrawing substituent, and no
increase of the µ value was observed as was shown for the
destabilized benzylic SN1 solvolyses.11f This result suggests
that the magnitude of the positive charge delocalized over the
aromatic ³-orbital is same as those for typical aryl-assisted
solvolyses. Therefore, the enlargement of r+ in the present
solvolysis should be responsible for the increase in the overlap
between the aryl ³-orbital and the ·*-orbital of the CÍL bond
that is caused by the decrease in the bond length between
the aryl carbon and the reaction center in the transition state.
This change in the transition-state structure implies a strong
aryl ³-electron participation, which assists the CÍL bond
cleavage in the deactivated intramolecular nucleophilic sub-
stitution reaction.
It might seem that the strong ³-electron participation
contradicts the little increase in the magnitude of positive
charge delocalized over aryl ³-orbital. This phenomenon is
probably due to the intramolecular SN2 characteristic of the
transition state of aryl-assisted solvolysis. The transition state
of SN2 reaction, having partial bonds between the reaction
center and the incoming nucleophile as well as the leaving
group, exhibits less sensitivity of a developed positive charge
to an electronic perturbation compared to that of non-assisted
(kc) solvolysis since the two partial bonds can be affected to
compensate for the perturbation. Such a characteristic is shown
in the theoretical calculations of the acid-catalyzed phenonium
ion formation from 2-arylethyl alcohols, where the positive
charge delocalized over the aryl ³-orbital is less affected by the
change of the aryl substituent in the transition state than in the
phenonium ion.12 Furthermore, the deactivation of the aceto-
lysis by the ¡-CN and CF3 groups would make the CÍL bond
in the transition state hard to dissociate. The SN2 transition state
involving high bond orders for both the incoming nucleophile
and the leaving group is often expressed as a “tight” transition
state, which exhibits development of a small positive charge.
By the extreme destabilization of 2-arylethyl solvolysis, its
transition state is considered to resemble the phenonium ion
intermediate, since the strongest ³-electron participation in the
aryl-assisted solvolysis is expected in the structure of the
phenonium ion intermediate. Here, the r+ value for the stability
of the destabilized phenonium ions is of interest. The stabilities
of the phenonium ions having no electron-withdrawing
substituent have experimentally been obtained by bromide
ion transfer reaction in the gas phase or by theoretical
calculation, and the LArSR analyses afforded r+ = 0.6213 or
r+ = 0.65,12 respectively. Mishima et al. concluded that the
agreement of these r+ values with r+ = 0.63 obtained for the
2
p
-MeO-m-Cl
3,4-Me2
p
-Me
1
X
3,5-Me2
δ+
CN
CF3
m
-Me
δ- OTf
H
– +
log k / kH = -3.28 (σo + 0.98 ∆σR)
0
-1.0
-0.5
0
0.5
σ scale
Figure 4. LArSR plot for the acetolysis of ¡-OTf at 130 °C:
closed circle, ·o; open circle, ·+; open square, ·app.
(r+ = 0.98).
substituents is explained by the large kš/kE rate ratios of over
50 to afford a negligible amount of Sty.
As shown in Figure 4, the substituent effect on kš was
successfully analyzed by using LArSR equation to result in
µ = Õ3.28 and r+ = 0.98 with a good precision of R = 0.990.
The obtained µ value of Õ3.28 is comparable to µ = Õ3.83
observed for the acetolysis rates of neophyl (=2,2-dimethyl-
2-arylethyl) brosylates at 75 °C5b or µ = Õ3.87 for the kÅ
acetolysis rates of 2-arylethyl tosylates (p-toluenesulfonates)
at 115 °C5a and is consistent with the proposed kÅ mechanism.
On the other hand, the r+ value is much larger than r+ = 0.57
for the acetolysis rates of neophyl brosylates or r+ = 0.63 for
the kÅ acetolysis rates of 2-arylethyl tosylates and is rather
comparable to r+ = 1.00 for the benzylic SN1 solvolysis rates
of t-cumyl (=1-methyl-1-arylethyl) chlorides.9
In general, the variation in r+ is interpreted as arising from
the following origins. One is a change in the transition-state
structure, which governs the overlap of the vacant orbital at the
reaction center and the aromatic ³-orbital. Therefore, t-cumyl
solvolysis with full overlap between the two orbitals results in
r+ of unity, while sterically distorted benzylic SN1 solvolyses
afford small r+ values.10 Moderate r+ values obtained for the
aryl-assisted solvolyses are thus ascribed to the partial overlap
between the aromatic ³-orbital and the ·*-orbital of the CÍL
bond.5,6 Another origin is the change in the stability of the
positive charge in the transition state, which affects the
magnitude of the positive charge to be delocalized over the
aromatic ³-orbital. By this origin, the r+ value increases with
the destabilization of the positive charge, which otherwise

258
Bull. Chem. Soc. Jpn. Vol. 82, No. 2 (2009)
Destabilized Acetolysis of 2-Arylethyl System
3
2
1
0
position has been shown for the solvolysis of 2-aryl-2-
(trifluoromethyl)ethyl nosylate (=m-nitrobenzenesulfonates)15
and is interpreted as being caused by the destabilization of the
transition state by the ¢-CF3 group. It should be noted that the
r+ value for the acetolysis of ¢-OTf is even larger than the
value of 0.77 for the acetolysis of 2-aryl-2-(trifluoromethyl)-
ethyl nosylates and is rather comparable to that for ¡-OTf. This
result suggests that the transition state of the acetolysis of ¢-
OTf is as strongly aryl-assisted as is the acetolysis of ¡-OTf.
p
-MeO
p
-MeS
p
-MeO-m-Cl
Conclusion
3,4-Me2
The acetolysis of ¡-OTf afforded Sty by the E2 mechanism
and phenyl-rearranged ¢-OAc and ¢-OTf through aryl-assisted
phenonium ion formation. The obtained ¢-OTf underwent
further aryl-assisted acetolysis to afford ¢-OAc as a sole
product. Kinetic analysis of these acetolysis successfully
afforded reaction rate constants kÅ¡, k¢, and kE as well as the
partitioning factor F in Scheme 1. The substituent effects on
kÅ¡ and k¢, were analyzed by using LArSR equation, resulting
µ = Õ3.28, r+ = 0.98 and µ = Õ3.48, r+ = 0.93, respectively.
The obtained µ values were comparable to those for the typical
aryl-assisted solvolyses but r+ values were much larger than
were those for the solvolyses. The enlargement of the r+ values
without an increase in the µ value suggests the changes in
the transition-state structures so that the overlap of the aryl
³-electrons and the ·*-orbital of the CÍL bond is more
significant. This change in the transition-state structure is
interpreted as that the CÍL bond cleavage in the deactivated
intramolecular nucleophilic substitution reaction of 2-arylethyl
solvolyses is assisted by the strong participation of the ¢-aryl
group.
p
-Me
X
3,5-Me2
δ+
δ-
CN
CF3
OTf
m
-Me
H
– +
log k / kH = -3.48 (σo + 0.93 ∆σR)
-1.0
-0.5
0
0.5
σ scale
Figure 5. LArSR plot for the acetolysis of ¢-OTf at 130 °C:
closed circle, ·o; open circle, ·+; open square, ·app.
(r+ = 0.93).
kÅ acetolysis rates of 2-arylethyl tosylates implies that the r+
values for the SN1 solvolyses are essentially identical to those
for the stabilities of the corresponding carbocation intermedi-
ates.12,13 Thus, the present result might suggest that the stability
of the phenonium ions destabilized by the CN and CF3 groups
affords a large r+ value that is close to unity. The r+ value for
the stability of destabilized phenonium ions can be evaluated
by a comparison with those obtained for FriedelÍCrafts
reactions, since the spiro structure of the phenonium ion
intermediate resembles those of the ·-complex intermediates in
the FriedelÍCrafts reactions. In fact, the r+ value of 0.98 for the
present acetolysis is in the range of 0.78 to 1.4, which is shown
for the FriedelÍCrafts reactions.14
Experimental
Synthesis.
A series of arylacetic acids were obtained by
Willgerodt reaction from corresponding acetophenones.16 Chlori-
nation of arylacetic acids with SOCl2 gave arylacetyl chlorides17
which were reacted with anhydrous trifluoroacetic acid and
pyridine to afford 1-aryl-3,3,3-trifluoro-2-propanones.18 Cyanation
of the ketones with sodium cyanide followed by the addition of
aqueous hydrochloric acid afforded 2-aryl-1-cyano-1-(trifluoro-
methyl)ethyl alcohol.19 The obtained cyanohydrins were reacted
with trfluoromethanesulfonic anhydride in the presence of pyridine
to give ¡-OTf.20 Typical synthetic procedures for p-Me derivatives
are described below.
The substituent effect on the solvolysis rates of ¢-OTf was
also successfully analyzed by using LArSR equation to result
in µ = Õ3.48 and r+ = 0.93 with a correlation coefficient of
R = 0.988, as shown in Figure 5. Because µ values of less than
Õ1 and an r+ value of zero have been shown in the substituent
effects on ks solvolyses of 2-arylalkyl substrates,3c,5 the
similarity of the substituent effects between for kš and for
k¢ suggests that the acetolysis of ¢-OTf also proceeds by the kÅ
mechanism. The obtained r+ value of 0.93 is somewhat smaller
than that for kš but is obviously larger than those for the
typical aryl-assisted solvolyses and indicates the significance of
the aryl ³-electrons in the transition state of the acetolysis of ¢-
OTf. It is interesting that enlargement of r+ is observed even
though the electron-withdrawing groups are attached to the ¢-
position but not to the ¡-position of the reaction center. The
enlargement of r+ by the electron-withdrawing group at the ¢-
Synthesis of p-Methylphenyl Acetic Acid. A mixture of p-
methylacetophenone (0.199 mol), sulfur (9.58 g), and morpholine
(0.299 mol) was heated at 130 °C for 2 days. The reaction mixture
was poured into 50 mL of hot ethanol, and the precipitates were
collected and washed with cold ethanol. The obtained morpholide
was hydrolyzed with 100 mL of 10% aq NaOH solution at 130 °C
for one day. Crude p-methylphenylacetic acid was obtained by the
acidification of the reaction mixture with hydrochloric acid and
was purified by recrystallization from benzene/n-hexane solution.
Synthesis of p-Methylphenylacetyl Chloride. Thionyl chlo-
ride (0.32 mol) was added to p-methylphenylacetic acid (0.16 mol)
and the mixture was refluxed for 1 h. The excess SOCl2 was
removed by distillation under reduced pressure, followed by the
addition of 15 mL of dry benzene and drying under vacuo.
Synthesis of 1-(p-Methylphenyl)-3,3,3-trifluoro-2-propa-
none. To a 20 mL of CH2Cl2 solution of trifluoroacetic anhydride

S. Usui et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 2 (2009)
259
(0.033 mL), p-methylphenylacetyl chloride (0.011 mol) dissolved
into 5 mL of CH2Cl2 was added at Õ60 °C. Dry pyridine (0.022
mol) was added dropwise to the solution and stirred for 3 h at
Õ60 °C. After the addition of 60 mL of H2O, the reaction mixture
was extracted with CH2Cl2. The crude product was distilled under
reduced pressure.
c) X. Creary, Acc. Chem. Res. 1985, 18, 3. d) X. Creary, A. C.
Hopkinson, E. Lee-Ruff, in ¡-Cbony1 Cations in Advances in
Carbocarion Chemistry, ed. by X. Creary, JAI Press, Greenwich,
1989, Vol. 1, pp. 45Í92. e) X. Creary, Chem. Rev. 1991, 91, 1625.
2
a) S. Winstein, B. K. Morse, E. Grunwald, K. C. Schreiber,
J. Corse, J. Am. Chem. Soc. 1952, 74, 1113. b) S. Winstein, K. C.
Schreiber, J. Am. Chem. Soc. 1952, 74, 2171. c) S. G. Smith, A. H.
Fainberg, S. Winstein, J. Am. Chem. Soc. 1961, 83, 618.
Synthesis of 2-Cyano-1-(p-methylphenyl)-3,3,3-trifluoro-2-
propanol.
1-(p-Methylphenyl)-3,3,3-trifluoro-2-propanone
(0.00532 mol) was dissolved into 30 mL of diethyl ether followed
by the addition of a 22 mL of NaCN (0.00681 mol) aq solution.
After 1 h of vigorous stirring, the reaction mixture was cooled by
ice bath and a 2.2 mL of 6 mol dmÕ3 aqueous hydrochloric acid
solution was added to the reaction mixture. Crude cyanohydrine
was obtained by extraction with diethyl ether and was purified with
the aid of conventional silica gel column chromatography.
3
a) J. M. Harris, F. L. Schadt, P. v. R. Schleyer, C. J.
Lancelot, J. Am. Chem. Soc. 1969, 91, 7508. b) H. C. Brown, C. J.
Kim, C. J. Lancelot, P. v. R. Schleyer, J. Am. Chem. Soc. 1970, 92,
5244. c) M. Goto, K. Funatsu, N. Arita, M. Mishima, M. Fujio, Y.
Tsuno, Mem. Fac. Sci., Kyushu Univ. Ser. C 1989, 17, 123.
4
a) Y. Yukawa, Y. Tsuno, Bull. Chem. Soc. Jpn. 1959, 32,
971. b) Y. Yukawa, Y. Tsuno, M. Sawada, Bull. Chem. Soc. Jpn.
1966, 39, 2274.
Synthesis of 1-Cyano-2-(p-methylphenyl)-1-(trifluorometh-
yl)ethyl Triflate.
A mixture of 2-cyano-1-(p-methylphenyl)-
5
a) M. Fujio, K. Funatsu, M. Goto, Y. Seki, M. Mishima, Y.
3,3,3-trifluoro-2-propanol (0.00487 mol) and dry pyridine
(0.00633 mol) in 3 mL of CH2Cl2 was cooled with an ice bath
under a nitrogen atmosphere. Trifluoromethanesulfonic anhydride
(0.00584 mol) and was added to the solution and was kept below
0 °C for 24 h. The trifluoromethanesulfonate ester was purified by
successive silica gel column chromatographies of the reaction
mixture.
Tsuno, Bull. Chem. Soc. Jpn. 1987, 60, 1091. b) M. Fujio, M.
Goto, M. Mishima, Y. Tsuno, Bull. Chem. Soc. Jpn. 1990, 63,
1121.
6
a) M. Goto, Y. Okusako, Y. Saeki, K. Yatsugi, Y. Tsuji, M.
Fujio, Y. Tsuno, Mem. Fac. Sci., Kyushu Univ. Ser. C 1992, 18,
233. b) M. Fujio, M. Goto, T. Dairokuno, M. Goto, Y. Seki, Y.
Okusako, Y. Tsuno, Bull. Chem. Soc. Jpn. 1992, 65, 3072. c) M.
Fujio, Y. Mada, M. Goto, Y. Seki, M. Mishima, Y. Tsuno, Bull.
Chem. Soc. Jpn. 1993, 66, 3015. d) M. Fujio, Y. Mada, M. Goto, Y.
Saeki, M. Mishima, Y. Tsuno, Bull. Chem. Soc. Jpn. 1993, 66,
3021.
Acetolysis. About 15 mg of ¡-OTf was dissolved into 1 mL of
commercially available acetic acid-d4 and ampouled into a
1H NMR tube under an Ar atmosphere. The sample tube was
immersed into a thermostated oil bath at 130 °C, and 1H and
19F NMR spectra were recorded at 20 °C by using a Varian Unity
Plus 500. The products were identified by NMR spectra, and
fractions of substrate and products at each reaction time were
determined from their signal integrals in 19F NMR spectra. NMR
signals of the solvent and trifluoromethylbenzene were used as
internal references for 1H and 19F NMR spectroscopies, respec-
tively. Typical spectral data of the substrate and solvolysis
products for the acetolysis of p-Me derivative are shown below.
Spectral Data of 1-Cyano-2-(p-methylphenyl)-1-(trifluoro-
methyl)ethyl Trifluoromethanesulfonate. 1H NMR (500 MHz,
CD3COOD): ¤ 7.32 (2H, d, J = 8.06 Hz, ArH), 7.26 (2H, d, J =
8.06 Hz, ArH), 3.61 (2H, ABq, J = 14.7 Hz, Ť = 0.0049, CH2),
2.36 (3H, s, CH3); 19F NMR (470 MHz, CD3COOD): ¤ Õ75.3 (3F,
s, CCF3), Õ77.7 (3F, s, OSO2CF3).
Spectral Data of 2-Cyano-2-(p-methylphenyl)-2-(trifluoro-
methyl)ethyl Acetate. 1H NMR (500 MHz, CD3COOD): ¤ 7.20Í
7.60 (4H, m, ArH), 4.86 (2H, ABq, J = 11.6 Hz, Ť = 0.0869,
CH2), 2.37 (3H, s, CH3); 19F NMR (470 MHz, CD3COOD): ¤
Õ71.5 (3F, s, CCF3).
Spectral Data of 2-Cyano-2-(p-methylphenyl)-2-(trifluoro-
methyl)ethyl Trifluoromethanesulfonate. 1H NMR (500 MHz,
CD3COOD): ¤ 7.20Í7.60 (4H, m, ArH), 5.18 (2H, ABq, J = 11.0
Hz, Ť = 0.153, CH2), 2.42 (3H, s, CH3); 19F NMR (470 MHz,
CD3COOD): ¤ Õ75.9 (3F, s, OSO2CF3), Õ70.8 (3F, s, CCF3).
Spectral Data of 1-(p-Methylphenyl)-2-(trifluoromethyl)-
acrylonitrile. 1H NMR (500 MHz, CD3COOD): ¤ 7.87 (2H, d,
J = 8.0 Hz, ArH), 7.80 (1H, s, ArCH), 7.58 (2H, d, J = 8.0 Hz,
ArH), 2.39 (3H, s, CH3); 19F NMR (470 MHz, CD3COOD): ¤
Õ65.2 (3F, s, CCF3).
7
a) D. J. Cram, J. Am. Chem. Soc. 1964, 86, 3767. b) C. J.
Lancelot, D. J. Cram, P. v. R. Schleyer, in Phenonium Ions in
Carbonium Ions, ed. by G. A Olah, P. v. R. Schleyer, Wiley, New
York, 1972, Vol. 3, pp. 1347Í1483.
8
879.
9
K. Yamaoka, Y. Tanigawa, T. Uno, J. Pharm. Dyn. 1981, 4,
a) H. C. Brown, Y. Okamoto, J. Am. Chem. Soc. 1957, 79,
1913. b) H. C. Brown, in A Quantitative Treatment of Directive
Effects in Aromatic Substitution in Advances in Physical Organic
Chemistry, Academic Press, New York, 1963, Vol. 1, pp. 35Í154.
10 a) M. Fujio, T. Miyamoto, Y. Tsuji, Y. Tsuno, Tetrahedron
Lett. 1991, 32, 2929. b) M. Fujio, H. Nomura, K. Nakata, Y. Saeki,
M. Mishima, S. Kobayashi, T. Matsushita, K. Nishimoto, Y.
Tsuno, Tetrahedron Lett. 1994, 35, 5005. c) M. Fujio, M. Ohe, K.
Nakata, Y. Tsuji, M. Mishima, Y. Tsuno, Bull. Chem. Soc. Jpn.
1997, 70, 929.
11 a) M. Fujio, T. Adachi, Y. Shibuya, A. Murara, Y. Tsuno,
Tetrahedron Lett. 1984, 25, 4557. b) A. Murata, M. Goto, R.
Fujiyama, M. Fujio, Y. Tsuno, Mem. Fac. Sci., Kyushu Univ.,
Ser. C 1988, 16, 225. c) A. Murata, M. Goto, R. Fujiyama, M.
Mishima, M. Fujio, Y. Tsuno, Bull. Chem. Soc. Jpn. 1990, 63,
1129. d) A. Murata, S. Sakaguchi, R. Fujiyama, M. Mishima, M.
Fujio, Y. Tsuno, Bull. Chem. Soc. Jpn. 1990, 63, 1138. e) M. Fujio,
M. Goto, T. Susuki, I. Akasaka, M. Mishima, Y. Tsuno, Bull.
Chem. Soc. Jpn. 1990, 63, 1146. f) Y. Tsuno, A. Murata, M. Goto,
M. Fujio, in Substituent Effect on the Solvolysis of 1-Aryl-1-
(trifluorokethyl)ethyl Triflate in Studies in Organic Chemistry, ed.
by M. Kobayashi, Elsevier, Amsterdam, 1986, Vol. 31, pp. 167Í
174.
12 S. C. Ammal, M. Mishima, H. Yamataka, J. Org. Chem.
2003, 68, 7772.
13 Mustanir, M. Mishima, M. Fujio, Y. Tsuno, Bull. Chem.
Soc. Jpn. 1998, 71, 1401.
References
1
a) P. G. Gassman, T. T. Tidwell, Acc. Chem. Res. 1983, 16,
279. b) T. T. Tidwell, Angew. Chem., Int. Ed. Engl. 1984, 23, 20.
14 a) P. B. D. de la Mare, J. Chem. Soc. 1954, 4450. b) L. M.

260
Bull. Chem. Soc. Jpn. Vol. 82, No. 2 (2009)
Destabilized Acetolysis of 2-Arylethyl System
Stock, F. Baker, J. Am. Chem. Soc. 1962, 84, 1661. c) H. C.
Brown, G. Goldman, J. Am. Chem. Soc. 1962, 84, 1650. d) H. C.
Brown, A. H. Neyens, J. Am. Chem. Soc. 1962, 84, 1655. e) H. C.
Brown, G. Marino, J. Am. Chem. Soc. 1962, 84, 1658.
15 M. Okamura, K. Hazama, M. Ohta, K. Kato, T. Horaguchi,
A. Ohno, Chem. Lett. 1997, 973.
16 a) R. D. Campbell, N. H. Cromwell, J. Am. Chem. Soc.
1955, 77, 5169. b) V. L. Bell, N. H. Cromwell, J. Org. Chem.
1958, 23, 789.
17 C. F. H. Allen, J. R. Byers, W. J. Humphlett, in Org.
Syntheses, ed. by N. Rabjohn, Wiley, New York, 1967, Coll.
Vol. 4, pp. 739Í743.
18 J. Boivin, L. E. Kaim, S. Z. Zard, Tetrahedron 1995, 51,
2573.
19 E. L. Fliel, J. P. Freeman, Org. Synth. 1967, Coll. Vol. 4,
58.
20 K. Takeuchi, M. Yoshida, Y. Ohga, A. Tsugeno, T.
Kitagawa, J. Org. Chem. 1990, 55, 6063.