Transformation of benzonitrile into benzyl alcohol and benzoate esters in supercritical alcohols

Article abstract of DOI:10.1016/j.tet.2008.04.029

The reactions of benzonitrile in supercritical methanol, ethanol, and 2-propanol were investigated under non-catalytic conditions. In supercritical methanol, benzonitrile was converted to methyl benzoate in high yield. The esterification reaction also occurred in supercritical ethanol to afford ethyl benzoate in moderate yield. The esterification could occur via a route analogous to the Pinner reaction. On the other hand, benzonitrile in supercritical 2-propanol yielded no ester. Benzyl alcohol was the major product in supercritical 2-propanol. We investigated the reaction of the C{double bond, long}N bond in supercritical 2-propanol. In supercritical 2-propanol, N-benzylideneaniline was transferred to the reduction product (N-benzylaniline) and hydrolysis products (benzyl alcohol and aniline). The hydrolysis reaction was restricted when the reaction was carried out in supercritical 2-propanol with a low water content. This indicates that the water in the 2-propanol acts as a reagent for the hydrolysis of the C{double bond, long}N bond. These results suggested the following reaction process: C₆H₅C{triple bond, long}N→C₆H₅CH{double bond, long}NH→C₆H₅CHO→C₆H₅CH₂OH.

Full text of DOI:10.1016/j.tet.2008.04.029

Tetrahedron 64 (2008) 5699–5702
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Transformation of benzonitrile into benzyl alcohol and benzoate esters
in supercritical alcohols
,
b
,
b
c
b,
*
Takashi Kamitanaka a , Kenji Yamamoto , Tomoko Matsuda , Tadao Harada
*
a Industrial Research Center of Shiga Prefecture, Kamitoyama, Ritto, Shiga 520-3004, Japan
b Department of Materials Chemistry, Ryukoku University, Seta, Otsu, Shiga 520-2194, Japan
c Department of Bioengineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The reactions of benzonitrile in supercritical methanol, ethanol, and 2-propanol were investigated under
non-catalytic conditions. In supercritical methanol, benzonitrile was converted to methyl benzoate in
high yield. The esterification reaction also occurred in supercritical ethanol to afford ethyl benzoate in
moderate yield. The esterification could occur via a route analogous to the Pinner reaction. On the other
hand, benzonitrile in supercritical 2-propanol yielded no ester. Benzyl alcohol was the major product in
supercritical 2-propanol. We investigated the reaction of the C]N bond in supercritical 2-propanol. In
supercritical 2-propanol, N-benzylideneaniline was transferred to the reduction product (N-benzylani-
line) and hydrolysis products (benzyl alcohol and aniline). The hydrolysis reaction was restricted when
the reaction was carried out in supercritical 2-propanol with a low water content. This indicates that the
water in the 2-propanol acts as a reagent for the hydrolysis of the C]N bond. These results suggested the
following reaction process: C6H5C^N/C6H5CH]NH/C6H5CHO/C6H5CH2OH.
Received 28 January 2008
Received in revised form 7 April 2008
Accepted 8 April 2008
Available online 11 April 2008
Keywords:
Supercritical alcohol
Esterification
Hydrolysis
Pinner reaction
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
However, no reactions of the C^N bonds with supercritical alco-
hols have been reported. We now report the reactions of benzo-
Supercritical or high-temperature water is a candidate reagent
for the transformation of nitrile into the corresponding amide or
carboxylic acid at high temperature.1 Izzo et al. investigated
the kinetics and mechanisms for the hydrolysis of aliphatic and
aromatic nitriles in high-temperature water.2 They proposed an
autocatalytic mechanism. This process requires no further addition
of a catalyst to promote the reaction because of high acidity of the
supercritical water.
nitrile with supercritical alcohols to afford benzoate esters or/and
benzyl alcohol. The preferential products were dependent on the
kind of supercritical alcohol.
The critical conditions of the alcohols used in this study are as
follows: methanol (critical temperature Tc¼513 K, critical pressure
pc¼8.1 MPa, critical density rc¼0.272 g cmꢀ3), ethanol (Tc¼516 K,
pc¼6.3 MPa, rc¼0.276 g cmꢀ3), and 2-propanol (Tc¼508 K, pc¼
4.8 MPa, rc¼0.273 g cmꢀ3).
Supercritical alcohols tend to be reactive with nitriles as well as
supercritical water. Supercritical alcohols function as reducing
agents for ketones and aldehydes.3–5 We have reported the direct
additions of alcohol molecules to alkenes or alkynes to form a car-
bon–carbon bond.6 Poly(ethylene terephthalate) is depolymerized
by methanolysis in supercritical methanol.7 Surprisingly, these re-
actions are carried out under non-catalyzed conditions. This in-
dicates that supercritical alcohols have high reactivities toward
unsaturated bonds.
2. Results and discussion
2.1. Reactions of benzonitrile in supercritical methanol,
ethanol, and 2-propanol
The behavior of benzonitrile in supercritical methanol, ethanol
or 2-propanol was examined in detail, and it was found that the
transformation of benzonitrile occurred in the supercritical alco-
hols. The preferential product was strongly dependent on the kind
of supercritical alcohol. The time courses of the reactions of ben-
zonitrile in supercritical methanol, ethanol, and 2-propanol are
shown in Figure 1a–c, respectively. The rate of disappearance of the
benzonitrile in supercritical methanol was much higher than that
in supercritical ethanol or supercritical 2-propanol. Benzonitrile in
supercritical methanol exclusively afforded methyl benzoate
As mentioned above, the reactions of the C]O, C]C, C^C or
COOR group with supercritical alcohols have been reported.
* Corresponding authors. Tel.: þ81 77 558 1500; fax: þ81 77 558 1373 (T.K); tel.:
þ81 77 543 7461; fax: þ81 77 543 7483 (T.H).
E-mail addresses: kamitanaka.takashi@shiga-irc.go.jp (T. Kamitanaka), harada@
rins.ryukoku.ac.jp (T. Harada).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.04.029

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T. Kamitanaka et al. / Tetrahedron 64 (2008) 5699–5702
Figure 1. Time courses of the reactions of benzonitrile in supercritical (a) methanol, (b) ethanol, and (c) 2-propanol at 623 K; , benzonitrile, C benzyl alcohol, - benzoate ester.
(around 95% yield). On the other hand, the major product of
the reactions between benzonitrile and supercritical ethanol or
2-propanol was benzyl alcohol. The reactions in supercritical
2-propanol afforded no ester. We found that the esterification also
proceeded for an aliphatic nitrile, i.e., lauronitrile, in supercritical
methanol. However, the maximum yield was much lower than that
for benzonitrile. The yield was 24% at 623 K for a 6-h reaction.
The effects of the density of supercritical alcohol on the con-
version of benzonitrile and yield of benzoate ester were in-
vestigated by carrying out the reactions of benzonitrile in
supercritical methanol. These results are shown in Table 1. At the
reaction time of 5 h, an increase in the density of supercritical
methanol (0.20/0.30 g cmꢀ3) resulted in a drastic increase in the
conversion (39/94%) and the yield (31/83%).
bond, and the primary or secondary alcohol functions as an alco-
holysis agent for the C^Nþ bond. The resulting intermediate (hy-
drochloride salt of iminoester) can be converted into the carboxylic
ester with H2O and HCl, which functions as a catalyst in this step.
Based on the mechanism for the Pinner reaction, the following
mechanism can be proposed for the esterification of benzonitrile in
supercritical methanol (Scheme 2). During the first step, pro-
tonation on the C^N nitrogen and attack of the alkoxide ions in an
alcoholic solution to the C^N carbon occur to form an imino ester.
The imino ester is then hydrolyzed to a carboxylic ester with water
in the reaction system.
NH
-OR
ROH
C
C
N
OR
2.2. Mechanistic aspects
H2O
2.2.1. Esterification
O
C
There have been various reports on the transformation of the
C^N bond into COOR. One of the well-known reactions is the
Pinner reaction.8,9 When a nitrile is treated with hydrochloric acid
in an alcohol, the nitrile is converted into an ester. Scheme 1 shows
a plausible mechanism. The HCl functions as a Hþ donor to the C^N
OR
Scheme 2. Plausible mechanism for the esterification of benzonitrile using super-
critical alcohol.
The concentrations of the alcohols are 24.7 mol/l for methanol,
17.2 mol/l for ethanol, and 13.1 mol/l for 2-propanol at 298 K. In
addition, Reeve et al. reported that the relative acidity of the alco-
hols for methanol, ethanol, and 2-propanol are 4.4, 1.0, and 0.24,
respectively.10 These indicate that the concentration of alkoxide ion
in methanol is much higher than those in ethanol and 2-propanol.
The alkoxide concentration order may also be valid for the alcohols
in the supercritical state. It can be assumed that the high concen-
tration of methoxide ion in supercritical methanol is responsible for
the rapid formation of methyl benzoate. On the other hand, in su-
percritical ethanol, the concentration of the alkoxide ion is much
lower, and then the rate of esterification is slower; it is likely that
another reaction (benzyl alcohol formation) also occurs in parallel
to the esterification. In supercritical 2-propanol, the concentration
of the alkoxide ion may be too low for the esterification. Indeed,
acetone is converted into 2,2-dimethoxypropane with a high se-
lectivity through attack on the carbonyl carbon by methoxide ions
in supercritical methanol,11 whereas no acetal was obtained in
supercritical 2-propanol.3–5 Steric hindrance with alkyl
substituents of alcohols might also be ascribed to the product dis-
tribution; the more bulky substituents there are at the hydroxyl-
bearing carbon, the less likely the alcohol will approach the C^N
carbon. From the viewpoint of steric-hindrance, the reactivity order
is also methanol>ethanol>2-propanol. This is the same order as
that of the alkoxide concentration mentioned above.
Table 1
Effects of the density of supercritical methanol on conversion of benzonitrile and
yield of methyl benzoate
Densitya (g cmꢀ3
)
Conversionb (%)
Yieldb (%)
0.20
0.25
0.30
39
75
94
31
68
83
Reaction conditions: temperature 623 K, reaction time 5 h.
a
Density of methanol solution in the reactor tube during the reaction.
b
Conversion and the yield of methyl benzoate were determined by gas
chromatography.
HCl
R
C
NH
Cl
R
C
N
R'
O
H
nucleophilic attack
NH2
O
Cl
hydrolysis
R
OR'
intermediate
Scheme 1. Plausible mechanism for esterification of nitriles (Pinner reaction).
R
OR'

T. Kamitanaka et al. / Tetrahedron 64 (2008) 5699–5702
5701
2.2.2. Benzyl alcohol forming reaction
H
N
We reported the non-catalytic reduction of carbonyls to the
corresponding alcohols using supercritical 2-propanol.3–5 This in-
volves the simultaneous hydrogen transfer via a six-membered
transition state analogous to that of the Meerwein–Ponndorf–
Verley reduction (Scheme 3). It could be expected that the re-
duction of nitriles to the corresponding amines occurs by a similar
mechanism. However, no amine generation was observed in the
reactions of benzonitrile in supercritical 2-propanol (Fig. 1c). Al-
ternatively, benzyl alcohol was obtained as the main product in 43%
yield for a 40-h reaction. Concerning the reduction of nitriles
to alcohols, Takahashi et al. reported that the reaction of nitriles
in 2-propanol over hydrous zirconium oxide in the vapor phase
afforded the corresponding alcohols.12 These facts suggest that it is
unlikely for nitriles to be reduced to the corresponding amines by
alcohols.
N
(1)
N-Benzylideneaniline
N-Benzylaniline
(1) Reduction
(2) Hydrolysis
(2)
O
(1)
NH2
H
OH
Benzaldehyde
Benzylalcohol
Aniline
Scheme 4. Plausible reactions of N-benzylideneaniline with supercritical 2-propanol.
It is well known that the transformation of C6H5CH]NH to
C6H5CH]O is extremely easy in the presence of water. Neverthe-
less, there was no detectable peak of benzaldehyde in the GC
analysis.15 This finding suggests that C6H5CH]O readily reacts with
supercritical 2-propanol to yield C6H5CH2OH, and the step of
C6H5C^N to C6H5CH^NH is the rate-determining one in the
transformation of C6H5C^N to C6H5CH2OH.
H
O
O
R
CH3
CH3
H
O
OH
R'
H
R'
R
R
R'
The deuterium tracer study using (CH3)2CD(OH) was applied to
the reactions of benzonitrile with supercritical 2-propanol with the
expectation of proving the reaction route from benzonitrile to
benzyl alcohol via C6H5CH]NH and C6H5CH]O. If the trans-
formation of benzonitrile to benzyl alcohol proceeds through the
above route, the two D atoms will be incorporated into the benzylic
position of the benzyl alcohol as shown in Scheme 5. The results are
shown in Table 3. The integration of the peak area for the benzylic
position on the 1H NMR spectrum suggested that deuterium atom
was indeed incorporated into the benzylic position by around 80%.
No H/D exchange occurred on the benzyl alcohol, when it was
treated with supercritical (CH3)2CD(OH) at 623 K (entry 2 in Table
3). This fact indicated that the deuterium atom was incorporated
into the benzyl alcohol during the reaction route from benzonitrile
to benzyl alcohol. These results support the idea that the benzyl
O
OH
H
H3C
CH3
H3C
CH3
Scheme 3. Meerwein–Ponndorf–Verley type reduction of ketone using supercritical 2-
propanol.
Taking into account that the C]O bond is hydrogenated to CH–
OH by supercritical alcohols, the C^N bond would be hydroge-
nated to CH]NH by supercritical alcohols. Thus, it can be presumed
that benzonitrile in supercritical alcohol is transformed into the
benzyl alcohol through the following route: C6H5C^N/
C6H5CH]NH/C6H5CH]O/C6H5CH2OH. Imines can be easily
hydrolyzed to the corresponding aldehydes and amines.13 Hence,
the transformation of C6H5CH]NH to C6H5CH]O will occur with
H2O in 2-propanol (less than 0.2%). Unfortunately, C6H5CH]NH is
unstable for investigating its reactivity. We selected substituted
C6H5CH]NC6H5 (N-benzilideneaniline) instead of naked
C6H5CH]NH to investigate the reactivity of the C]N bond in su-
percritical 2-propanol, because the C]N bond in substituted
C6H5CH]NC6H5 is more resistant than in the naked C6H5CH]NH
due to conjugation of the C]N bond with two phenyl groups. Table
2 shows the results of the reaction of C6H5CH]NC6H5 in super-
critical 2-propanol at 623 K.
N-Benzylideneaniline was converted into N-benzylaniline,
benzyl alcohol, and aniline. The resistance of N-benzylidene-
aniline to hydrolysis would result in the formation of N-benzyl-
aniline. Plausible reaction routes of N-benzylideneaniline to
N-benzylaniline, aniline, and benzyl alcohol are shown in Scheme 4.
To investigate the hydrolysis step for the reaction of benzonitrile
to benzyl alcohol, we carried out the reaction of N-benzylidene-
aniline in dehydrated 2-propanol (H2O content: less than 0.005%).14
This result is also shown in Table 2. The generation of benzyl alcohol
and aniline was suppressed under the dehydrated conditions. This
indicates that the water in the reaction system functions as a
reagent for the benzyl alcohol formation.
H
H
O
H
O
C
D
MPV-type
reduction
hydrolysis
C
NH
C
N
NH2
D
(CH3)2CD(OH)
(CH3)2C=O
-NH3
O
D
D
MPV-type
reduction
D
HO
(CH3)2C=O
(CH3)2CD(OH)
Scheme 5. Plausible mechanism for the benzyl alcohol formation (deuterium trace
reaction).
Table 3
Deuterium contents at benzylic position of benzyl alcohola
Entry
Reaction
D at benzyl
position (%)
Table 2
1b
2c
Ph–CN/Ph–CH2OH
Ph–CH2–OH in sc (CH3)2CD(OH)
80
0
Reaction of N-benzylideneaniline in supercritical 2-propanol
Alcohol
Conversion Yield (%)
(%)
a
Deuterium contents were quantified by 1H NMR.
Benzonitrile was reacted in supercritical (CH3)2CD(OH) at 623 K for 8 h. The
b
N-Benzyl aniline Aniline Benzyl alcohol
benzyl alcohol was isolated by thin layer chromatography (Merck silica gel pre-
coated plate, eluent: n-hexane/AcOEt¼5:1, Rf¼0.24 (benzyl alcohol), 0.45
(benzonitrile)).
2-Propanol
Dehydrated 2-propanol 67
84
32
41
23
4
29
3
c
Reaction conditions: temperature 623 K, reaction time 3 h.
(CH3)2CD(OH) solution of benzyl alcohol was maintained at 623 K for 8 h.

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T. Kamitanaka et al. / Tetrahedron 64 (2008) 5699–5702
alcohol forming reaction mainly proceeds via the route shown in
Scheme 5.
set to zero when the temperature reached the desired value. The
temperature in the autoclave reached 623 K in 20 min. After
a specific reaction time had elapsed, the autoclave was removed
from the furnace and cooled by a strong air stream to quench the
reaction.
3. Conclusions
The treatment of benzonitrile with supercritical methanol,
ethanol or 2-propanol resulted in the formations of the benzoate
ester or/and benzyl alcohol. The esterification of benzonitrile in
supercritical methanol and ethanol occurred in high (up to 93%)
and low (up to 20%) yields, respectively. On the other hand, no ester
generation was observed in supercritical 2-propanol. The rate of
ester formation may depend on the amount of the alkoxide ion in
the alcohol solution. The transformation of benzonitrile into esters
is explained on the basis of a mechanism analogous to that for
the Pinner reaction. The benzyl alcohol generation occurred in
supercritical 2-propanol and ethanol. The study under dehydrated
conditions and the deuterium tracing one suggested that
the transformation from benzonitrile to benzyl alcohol proceeded
via the route of C6H5C^N/C6H5CH]NH/C6H5CH]O/
C6H5CH2OH.
4.3. Analysis
A 25
ml portion of the reaction solution in the tube was poured
into a test tube and a 25
ml aliquot of the solution of bibenzyl (in-
ternal standard; 10 mmol dmꢀ3) was added to the tube. The solu-
tion was subjected to analysis by the gas chromatography
(Shimadzu GC-15A, capillary column, i.d. 0.32-mm, liquid phase
DB-17, film thickness 0.5-mm, length 30-m). The quantitative
analyses were performed by the internal standard method. The
identification of the products was performed by GC–MS and 1H
NMR analyses, if necessary.
Supplementary data
4. Experimental section
4.1. Materials
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.04.029.
References and notes
Materials were purchased from Nacalai Tesque, Inc. and used
without further purification. Dehydrated 2-propanol was pur-
chased from Wako Pure Chemical Industry. The water content was
below 50 ppm.
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