Chlorobenzyl alcohols from chlorobenzyl chlorides via corresponding benzoate esters: Process development aspects

Article abstract of DOI:10.1021/op9900535

Kinetic studies in conversion of benzyl chlorides to corresponding alcohols via the benzoates are presented in this paper. The esterification reaction of 2-chlorobenzyl chloride, 4-chlorobenzyl chloride, 2,4-dichlorobenzyl chloride and benzyl chloride with aqueous sodium benzoate in the presence of phase transfer catalysts was investigated. The parameters studied are stirring speed, catalysts, the catalyst loading, temperature and the concentration of aqueous phase. The esterification reaction follows pseudo-first-order kinetics. The esters, were hydrolysed with and without a phase transfer catalyst to give corresponding benzyl alcohols without involving respective dibenzyl ethers. Material balance for the laboratory batch process of each chlorobenzyl alcohol has also been presented. A recycle strategy presented is shown to be effective in terms of alkali and benzoic acid consumption as the reactants are consumed to near stoichiometric levels.

Full text of DOI:10.1021/op9900535

Organic Process Research & Development 2000, 4, 23−29
Chlorobenzyl Alcohols from Chlorobenzyl Chlorides via Corresponding Benzoate
Esters: Process Development Aspects
S. R. Joshi and S. B. Sawant*
Department of Chemical Technology, UniVersity of Mumbai, Matunga, Mumbai - 400 019, India
Abstract:
chlorobenzyl alcohols by this strategy. Also, the information
regarding chlorobenzyl benzoate esters is scanty.5 Thus, the
study of the reaction of benzyl chloride and chlorobenzyl
chlorides with sodium benzoate in the presence of a phase
transfer catalyst is investigated. The main focus of this study
was to develop a commercially viable process for the
synthesis of chlorobenzyl alcohols without involving the
corresponding dibenzyl ether. The substrates examined are
benzyl chloride (BnCl), 4-chlorobenzyl chloride (PCBC),
2-chlorobenzyl chloride (OCBC), and 2,4-dichlorobenzyl
chloride (DCBC).
Mechanism and Kinetics for the Formation of Ester.
The following mechanism shows the formation of chlo-
robenzyl benzoate from chlorobenzyl chloride when a
trialkylamine (NR3) is used as a phase transfer catalyst.
Chlorobenzyl chlorides are represented by R1Cl where Rl )
2-chlorobenzyl, 4-chlorobenzyl or 2,4-dichlorobenzyl and
R1N+R3 by Q+,
Kinetic studies in conversion of benzyl chlorides to correspond-
ing alcohols via the benzoates are presented in this paper. The
esterification reaction of 2-chlorobenzyl chloride, 4-chlorobenzyl
chloride, 2,4-dichlorobenzyl chloride and benzyl chloride with
aqueous sodium benzoate in the presence of phase transfer
catalysts was investigated. The parameters studied are stirring
speed, catalysts, the catalyst loading, temperature and the
concentration of aqueous phase. The esterification reaction
follows pseudo-first-order kinetics. The esters, were hydrolysed
with and without a phase transfer catalyst to give corresponding
benzyl alcohols without involving respective dibenzyl ethers.
Material balance for the laboratory batch process of each
chlorobenzyl alcohol has also been presented. A recycle strategy
presented is shown to be effective in terms of alkali and benzoic
acid consumption as the reactants are consumed to near
stoichiometric levels.
R1Cl
+ R3N h
Introduction
chlorobenzyl chloride
Chlorobenzyl alcohols have been widely used in the
pharmaceutical and perfumery industries. Chlorobenzyl al-
cohols can be synthesized by hydrolysis of corresponding
benzyl chlorides with an alkali hydroxide or carbonate.
However, hydrolysis of benzyl chloride with sodium hy-
droxide in the presence of a phase transfer catalyst produces
substantial quantities of dibenzyl ether.1,2 Hydrolysis of
benzyl chloride with sodium bicarbonate involves 10-12%
dibenzyl ether.3 Bayer A. G. has patented a process in which
benzyl chloride is hydrolysed with water.4 The formation of
dibenzyl ether in this process is low, and the byproduct HCI
is subjected to electrolysis to generate Cl2 which is used to
produce benzyl chloride from toluene. The process involves
three separate distillation steps. This strategy may not be
suitable for low-volume products because of the extensive
instrumentation required and the expensive material of
construction. Also the separation of benzyl chloride and
benzyl alcohol is rather difficult. The possibility of formation
of dibenzyl ether can be avoided if benzyl chloride is
esterified and then the ester is hydrolysed. The literature has
shown few practical methods regarding the manufacture of
[Q+Cl-]
quaternary ammonium chloride
(organic phase) (1)
In the first step, quaternisation of the tertiary amine takes
place in the organic phase. This quaternary ammonium salt
actually acts as the phase transfer catalyst.
[Q+Cl-]org + C6H5COO-aq h [Q+C6H5COO-]org
Cl-
(both phases) (2)
+
aq
In the second step extraction of C6H5COO- ion into the
organic phase takes place.
C6H5COOR1
chlorobenzyl benzoate
[Q+C6H5COO-]org + R1Cl f
+
[Q+Cl-]org (organic phase) (3)
In the third step, chlorobenzyl benzoate is formed by the
reaction of extracted C6H5COO- with chlorobenzyl chloride.
Chlorobenzyl alcohol (R1OH) is formed by the following
reaction:
* To whom correspondence should be addressed
(1) Hwu, D. W.; Hwang, C.; Shih Y. P.; Chao, C. Ind. Eng. Chem. Res. 1992,
31, 177.
(2) Joshi, S. R.; Sawant, S. B.; Joshi, J. B. Org. Process Res. DeV. 1999, 3, 17.
(3) Ullmann’s Encyclopedia of Industrial Chemistry, 5th ed.; VCH Verlags-
gesellschaft mbH: Weinheim, 1985; Vol. A4.
C6H5COONa + H20 h C6H5COOH + Na+ +
OH- (aqueous phase) (4)
(4) Buysch, H. J.; Jonsen, U.; Ooms, P.; Hoffmann, E. G. (Bayer A. G.,
Germany). German Patent EP 781,748, 1997; Chem. Abstr. 1997, 127,
81236x.
(5) Walter, H. C. R.; Abram, G.; Russel K. F. J. Am. Chem. Soc. 1945, 67,
2154.
10.1021/op9900535 CCC: $19.00 © 2000 American Chemical Society and The Royal Society of Chemistry
Published on Web 12/23/1999
Vol. 4, No. 1, 2000 / Organic Process Research & Development
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23

This OH- formed in the aqueous phase is extracted into the
organic phase and reacts with benzyl chloride to give benzyl
alcohol.
Analysis. The reaction in the organic layer was monitored
by gas chromatography using a 2 m, 10% OV-17 column.
Nitrogen was the carrier gas, and the detector was FID. The
other parameters were as follows:
[Q+Cl-]org + OH-aq h [Q+OH-]org + Cl-
(5)
aq
injection temperature
detector temperature
nitrogen flow rate
temperature
350 °C
350 °C
30 mL/min
(1) 110 °C for 5 min, 110-275 °C
at the rate of 30 °C/min,
temperature 275 °C for 2 min
(for system containing benzyl
chloride, benzyl benzoate,
benzyl alcohol)
[Q+OH-]org + R1Cl f
+
R1OH
chlorobenzyl alcohol
[Q+Cl-]org (organic phase) (6)
programming
Chlorobenzyl alcohol is possibly formed by hydrolysis
of formed chlorobenzyl benzoate.
(2) 200 °C for 3.5 min,
200-290 °C at the rate of
30 °C/min, temperature
290 °C for 3.5 min (for
system containing DCBC,
corresponding ester,
[Q+OH-]org + C6H5COOR1 f
+
R1OH
chlorobenzyl alcohol
[Q+C6H5COO-]org (organic phase) (7)
and alcohol)
Chlorobenzyl alcohol is possibly also formed by the follow-
ing reaction which does not require any assistance of a phase
transfer catalyst:
(3) 170 °C for 2.5 min,
170-275 °C at the rate of
30 °C/min, temperature
275 °C for 3 min (for
system containing OCBC,
PCBC, and corresponding
esters and alcohols)
C6H5COONa
R1Cl + H2O f [R1O+HH Cl-]
8 R1OH +
NaCl + C6H5COOH (8)
Results and Discussion
The conversion of substrate (%) and yield of ester (%)
were determined by using following formulae:
When transfer of anions to the organic phase follows
extraction mechanism, first-order dependence of the rate of
reaction on both the substrate concentration and catalyst
concentration is observed.6,7 In such cases, a plot -ln(1 -
x) versus time is a straight line, where x is fractional
conversion of the substrate, defined as:
conversion of substrate (%) )
mol of substrate consumed
mol of substrate charged
× 100
yield of ester (%) )
mol of the substrate consumed
x )
mol of substrate consumed for the formation of ester
mol of the substrate charged
× 100
mol of substrate consumed
The slope of the line gives the observed pseudo-first-order
rate constant, kobs. Also a plot ln kobs versus ln C0 is a straight
line where C0 is the initial concentration of the catalyst.
The effect of the following variables on the conversion
of substrate was studied: (1) stirring speed, (2) catalysts,
(3) catalyst loading, (4) substrates, (5) temperature, (6)
concentration of sodium benzoate in aqueous layer.
Effect of Change in the Stirring Speed. A phase transfer
catalysed reaction is regarded as mass transfer rate-limited
when the rate of anion transfer across the interface is slower
compared to the rate of intrinsic reaction, while the same is
intrinsic reaction rate-controlled when the rate of anion
transfer across the interface is fast but the rate of intrinsic
reaction is slow. At the low stirring speed, the requirement
for sufficiently rapid mass transfer of the anions is not met,
and mass transfer rate-limited kinetics is observed. As we
increase the speed of stirring, the rate of mass transfer across
the interface increases and becomes faster than the intrinsic
reaction rate. Thus, at higher stirring speed, the reaction goes
from being mass transfer rate-limited to intrinsic reaction
rate-limited.
Experimental Section
Methods. All of the experiments were carried out in a
batch manner. A borosillicate glass reactor of 75 mm i.d.,
400 mL capacity, provided with a pitch-blade turbine down
flow impeller (25 mm diameter), and baffles were used.
Reaction temperature was maintained by using a constant-
temperature bath.
A predetermined quantity of aqueous sodium benzoate
was added to the reactor placed in the constant-temperature
bath. A measured quantity of benzyl chloride preheated to
the required temperature was then added, followed by
addition of the catalyst, and then the run was started. Very
small quantities of samples were withdrawn at predetermined
time intervals, and the reaction in the organic layer was
monitored by gas chromatography for the conversion of
substrate.
To investigate the effect of the speed of stirring, 4-chlo-
robenzyl benzoate (PCBnbzt) was synthesized by reacting
PCBC with aqueous sodium benzoate using tri-n-butylamine
as a catalyst. The experiments were performed at 100 °C.
Elimination of mass transfer resistance at 100 °C also ensures
that reactions at lower temperature under similar agitation
(6) Dehmlow, E. V.; Dehmlow S. S. Phase Transfer Catalysis, 3rd ed.; VCH
Verlagsgesellschaft mbH: Weinheim, 1993.
(7) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase Transfer Catalysis:
Fundamentals, Applications & Industrial PerspectiVes; Chapman & Hall,
Inc.: New York, 1994.
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Vol. 4, No. 1, 2000 / Organic Process Research & Development

Figure 1. Effect of different catalysts on the conversion of
PCBC. PCBC ) 0.3 mol. Sodium benzoate ) 216 mL, 1.73 M.
Temperature ) 70 °C. Catalyst ) 0.006 mol (2% of the organic
phase). Speed of stirring ) 2500 rpm.
Figure 2. Effect of catalyst concentration on the progress of
the reaction. PCBC ) 0.3 mol. Sodium benzoate ) 216 mL,
1.73 M. Temperature ) 100 °C. Catalyst ) Tri-n-butylamine.
Speed of stirring ) 2500 rpm.
conditions or speed of agitation are intrinsic reaction rate-
controlled. Sodium benzoate (216 mL of 1.73 M) and PCBC
(0.3 mol) were taken. The molar catalyst loading was 2% of
the organic phase. When experiments were performed for
1000 and 2500 rpm, there was no effect of speed of agitation
on the progress of the reaction. Thus, beyond the speed of
1000 rpm the reaction becomes intrinsic reaction rate-
controlled. However the further experiments were performed
at 2500 rpm to ensure that the effects of various operating
parameters are evaluated when the reaction is intrinsic
reaction rate-controlled. If experiments are performed at low
stirring speeds, the change in the reaction rate cannot be
attributed to the variable under investigation alone.
Effect of Different Catalysts. Experiments were carried
out at 70 °C with different catalysts. The catalysts used were
triethylamine (TEA), tri-n-butylamine (TBA), and triocty-
lamine (TOA). Molar loading of all the catalysts was 2% of
organic phase. PCBC (0.3 mol) and sodium benzoate (216
mL of 1.73 M) were used.
As can be seen in Figure l, whilst trioctylamine has
highest catalytic activity, followed by tri-n-butylamine, and
triethylamine has the lowest activity. The logarithm of
extraction constants of homologous series of quaternary
ammonium salts increased by a more or less constant factor
of about 0.54 per added C atom in the quaternary molecule.6
This result indicated the extractability of quaternary salts
increases as the lipophilic nature of the quaternary cation
increases. As the chain length of alkyl group in the quaternery
salt increases, its lipophilicity increases. Thus lipophilicity
of [Q+C6H5COO-] is lower when it is formed from triethy-
lamine and higher when it is formed from trioctylamine. The
concentration of the ion pair [Q+C6H5COO-] in the organic
phase increases as the lipophilicity of Q+ goes on increasing.
This increases the rate of consumption of PCBC by reaction
3. Similar results have been reported by Hwu et al8 for the
synthesis of benzyl acetate from benzyl chloride and tri-
alkylamine as the catalyst.
Effect of Catalyst Concentration. With a view to
investigate the effect of catalyst concentration the experi-
ments were performed at 100 °C using tributylamine as a
catalyst. PCBC (0.3 mol) was treated with sodium benzoate
solution (216 mL of 1.73 M) at the stirring speed of 2500
rpm. These conditions represent 25% molar excess of sodium
benzoate over PCBC. Further, at 2500 rpm stirring speed
the reaction is intrinsic reaction rate-controlled.
When for the reaction under investigation we plotted -ln-
(l - x) versus time we found that the reaction follows first-
order kinetics with respect to substrate concentration. Figure
2 shows the relationship of -ln(l - x) with time for different
catalyst loadings. As can be seen in Figure 2, for the same
batch time, the rate of consumption of PCBC increases as
the catalyst loading increases. We determined kobs for
different initial catalyst concentrations (C0). Figure 3 shows
ln kobs versus ln C0 plot for the experiments. A linear
relationship is obtained. This result indicates that consump-
tion of PCBC shows first-order dependence on the substrate
concentration (Figure 2) and the catalyst concentration
(Figure 3). In the previous sections it was shown that the
reaction is independent of stirring speed above 1000 rpm
and the reaction rate increases with increasing organophilicity
of Q+. All of these observations conclusively indicate an
extraction mechanism for transfer of C6H5COO- from the
aqueous to the organic phase.7
It is observed that in the absence of any phase transfer
catalyst, the reaction does take place to a remarkable extent.
Also, the yield of 4-chlorobenzyl alcohol corresponding to
77.5% conversion of PCBC was about 20%. This indicates
that the presence of PTC considerably enhances the rate of
formation of ester.
Effect of Change in the Substrate. Four different
substrates were examined, viz., PCBC, OCBC, DCBC, and
(8) Hwu, D. W.; Hwang, C.; Yeh, M. Y.; Jung, H. M.; Shih, Y. P. Ind. Eng.
Chem. Res. 1990, 29, 2214.
Vol. 4, No. 1, 2000 / Organic Process Research & Development
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25

Figure 3. Effect of catalyst concentration (ln kobs vs ln C0).
PCBC ) 0.3 mol. Sodium benzoate ) 216 mL, 1.73 M.
Temperature ) 100 °C. Catalyst ) Tri-n-butylamine. Speed
of stirring ) 2500 rpm.
Figure 5. Effect of temperature on the progress of the reaction.
PCBC ) 0.3 mol. Sodium benzoate ) 216 mL, 1.73 M. Catalyst
) Tri-n-butylamine, 0.006 mol. Speed of stirring ) 2500 rpm.
hence [Q+C6H5COO-] concentration in the organic phase
may not be the same in all cases.
Effect of Temperature. Figure 5 shows the effect of
temperature for the case of tri-n-butylamine as a catalyst and
PCBC as the substrate. The experiments were carried out
using 216 mL of 1.73 M aqueous sodium benzoate solution,
38 mL of substrate, and 0.006 mol tri-n-butylamine as a
catalyst. Figure 5 indicates the pseudo-first-order kinetics
for the reactions under consideration. For the experiments
performed at 70 and 80 °C we can see an induction period
of around 80 min, and then the reaction follows normal
pseudo-first-order kinetics. This induction period is probably
the outcome of low rate of quaternisation of tri-n-butylamine
with PCBC under the experimental condition. At 100 °C,
however, there is no induction period. Pseudo-first-order rate
constants were determined at 70, 80, and 100 °C. Similar
induction periods were also observed when OCBC and
DCBC were used as the substrates. Occurrence of induction
periods in the phase transfer catalysed reactions using
trialkylamines and benzyl chloride has already been re-
ported.1 Arrhenius plots were made for all substrates (Figure
6), and the energy of activation was determined for all the
substrates. The values of energies of activation are described
in Table 1. The high values of energy of activation also
confirm the absence of mass transfer resistance, and the
progress of the reaction is governed by the intrinsic reaction
in the organic phase.
Effect of Concentration of Aqueous Sodium Benzoate.
The effect of change in the aqueous phase concentration was
evaluated by treating 0.3 mol of PCBC with different
concentrations of sodium benzoate solutions, viz., 1.39, 1.73
and 2.78 M. The volume of aqueous phase was kept constant
(216 mL) in all three experiments. Tri-n-butylamine (0.006
mol) was used as the catalyst at 100 °C and 2500 rpm. Using
aqueous-phase concentration below 1.39 M was avoided as
it reduces the sodium benzoate/PCBC mole ratio below unity.
After the consideration of solubility of sodium benzoate in
water, the upper limit of concentration was decided. Figure
Figure 4. Progress of the reaction of PCBC, OCBC, DCBC,
and BnCl. Substrate ) 38 mL. Sodium benzoate ) 216 mL,
1.73 M. Temperature ) 100 °C. Catalyst ) Tri-n-butylamine,
0.006 mol. Speed of stirring ) 2500 rpm.
BnCl. Thirty-eight milliliters of each substrate (BnCl ) 0.33
mol, PCBC ) 0.3 mol, OCBC ) 0.3 mol, DCBC ) 0.27
mol) was treated with 216 mL of 1.73 M sodium benzoate
solution at 100 °C. Tri-n-butylamine (0.006 mol) was used
as catalyst. The volume of substrate was kept the same in
all of the experiments so as to have same concentration of
[Q+C6H5COO-] in the organic phase. It can be seen from
eq 3, that the rate of reaction depends on the concentration
of [Q+C6H5COO-] in the organic phase and we attempted
to keep it constant by maintaining the concentration of the
catalyst. Figure 4 shows the effect of change in substrate.
Benzyl chloride shows the highest reactivity. PCBC and
DCBC have almost the same reactivity, and OCBC has the
lowest reactivity. As the substrate changes, the structure of
quaternary ion changes. These quats may have different
extraction coefficients in the corresponding substrates and
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Vol. 4, No. 1, 2000 / Organic Process Research & Development

Table 2: Yield of chlorobenzyl alcohols in the esterification
reaction
%
conver
of
%
catalyst conc.
loading of aq
(%) phase (M)
yield of temp,
substrate substrate alcohol °C
catalyst
PCBC
PCBC
PCBC
PCBC
PCBC
PCBC
PCBC
98.54
98.45
99
51
10
87
76
4.23 100 TBA
1.77 100 TBA
2
4
8
2
2
2
2
4
4
1
2
2
1.73
1.73
1.73
1.73
1.73
1.73
1.73
2.78
1.39
1.73
1.39
2.78
1.73
1.73
1.73
1.73
1.73
6.7
n.da.
n.d.
n.d.
n.d.
n.d.
n.d.
6.5
4.6
6.2
20
100 TBA
70 TBA
70 TEA
70 TOA
80 TBA
100 TBA
100 TBA
100 TBA
100 TBA
100 TBA
100 no catalyst
100 TBA
100 TBA
100 TBA
PCBC 100
PCBC
PCBC
PCBC
PCBC
PCBC
OCBC
OCBC
DCBC
BnCI
99.5
91
98
99.2
77.5
93.9
99.7
99.2
99
5.4
4
n.d.
2
3
2
2
Figure 6. Arrhenius plot. Substrate ) 38 mL. Sodium benzoate
) 216 mL, 1.73 M. Catalyst ) Tri-n-butylamine, 0.006 mol.
Speed of stirring ) 2500 rpm.
16.5 100 TBA
a n.d. ) Not detected.
Table 1: Activation energies for the reaction between
chlorobenzyl chlorides and sodium benzoate in the aqueous
solution
reaction between PCBC and [Q+C6H5COO-], (reaction 3)
is the rate-determining step. Constant concentration of
C6H5COO- in the organic phase in all cases can show the
same reaction rate for all three concentrations of sodium
benzoate solutions studied. A similar result has been reported
by Bar et al,9 wherein the apparent extraction constant and
selectivity constant for formate and chloride in the presence
energy of activation
substrate
(kcal/mol)
PCBC
OCBC
DCBC
BnCI
13.4
15.6
19.3
18.88
of NHex+ and a large excess of formate do not change to
4
an appreciable extent with change in formate concentration
in the aqueous phase. We also performed the experiment in
the absence of sodium benzoate in the aqueous phase, other
reaction parameters being the same. After 12 h, the conver-
sion of PCBC was 60%, and the yields of corresponding
alcohol and corresponding dibenzyl ether were 90 and 10%,
respectively.
The yields of chlorobenzyl alcohols under various condi-
tions are listed in Table 2.
Hydrolysis of Esters
Comparison of Purified and Unpurified Esters. The
benzoates synthesized in the above study were subjected to
hydrolysis with dilute sodium hydroxide solution. 4-Chlo-
robenzyl benzoate (PCBnbzt) and 2,4-dichlorobenzyl ben-
zoate (DCBnbzt) formed in the above study were washed
with hot distilled water and recrystallized from methanol.
Their melting points were found to be 59 and 56 °C,
respectively. Recrystallized ester (0.15 mol) was treated with
75 mL of 2.5 M aqueous sodium hydroxide at 80 °C and
2500 rpm. The results are presented in Figure 8. In both
cases, the reaction initially proceeds sluggishly. After around
30% conversion of ester, the rate of reaction increases
rapidly. As the ester is reacted, corresponding amounts of
corresponding alcohol and sodium benzoate are formed. In
Figure 7. Effect of aqueous phase concentration on the
conversion of PCBC. PCBC ) 0.3 mol, Sodium benzoate ) 216
mL, Temperature ) 100 °C, Catalyst ) Tri-n-butylamine, 0.006
mol, Speed of stirring ) 2500 rpm.
7 shows the effect of aqueous phase concentration on the
progress of the reaction. As can be seen from Figure 7, the
progress of the reaction is not affected by the change in the
aqueous-phase concentration. In the concentration range
studied, it is possible that the change in the aqueous-phase
concentration does not effectively change the concentration
of [Q+C6H5COO-] in the organic phase. The intrinsic
(9) Bar R.; Karpuj-Bar, L.; Sasson Y.; Blum, J. Anal. Chim. Acta. 1983, 154,
313; Chem. Abstr. 1984, 100, 13338z.
Vol. 4, No. 1, 2000 / Organic Process Research & Development
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27

Scheme 1
phase. The ester formed in the first reaction is hydrolysed
in the second step using 25% molar excess of sodium
hydroxide. After the end of the hydrolysis reaction, the
aqueous phase contains this excess sodium hydroxide
together with 1 equiv of sodium benzoate formed. The excess
sodium hydroxide can be reacted with corresponding amount
of benzoic acid, and the aqueous phase can then be used for
the esterification step after proper dilution. One mole of ester
consumes one mole of sodium hydroxide, affording one mole
of the corresponding alcohol. Some benzoic acid still may
be lost during separation of the two phases and filtration,
and it may not be completely recovered. We decided to find
out the consumption of benzoic acid required for the whole
process and investigated the material balance. Scheme 1
shows the reactions carried out.
Substrate [A(organic) ) PCBC, OCBC, DCBC] (0.15
mol) was treated with sodium benzoate [F(aqueous)] (108
mL, 1.73 M) at 100 °C. Tri-n-butylamine was used as the
catalyst (0.003 mol in case of PCBC and DCBC, 0.0045 mol
in case of OCBC). After the reaction was allowed to continue
for 7 h, the reaction mixture was cooled to room temperature,
and the two layers were separated. The organic phase
[B(organic)] was washed with distilled water. After being
washed, the organic layer was dried by evaporating water at
110 °C and weighed and analysed. The organic phase
[B(organic)] was then treated with aqueous NaOH solution
[G(aqueous)] (75 mL, 2.5 M) at 80 °C. After the reaction
was complete, the reaction mixture was cooled to room
temperature, and the solid alcohol [D(organic)] was separated
by filtration, washed thoroughly with chilled distilled water,
dried under vacuum, and weighed and analysed. The gas
chromatographic analysis of all of the alcohols shows no
presence of corresponding chlorobenzyl chloride, ester, and
substituted dibenzyl ether. The melting points of crude
4-chlorobenzyl alcohol, 2-chlorobenzyl alcohol, and 2,4-
dichlorobenzyl alcohol were found to be 70, 69, and 56 °C,
respectively.
Figure 8. Hydrolysis of esters in the presence and absence of
a PTC. Ester ) 0. 15 mol. NaOH ) 75 mL, 2.5 M. Temperature
) 80 °C. Speed of stirring ) 2500 rpm.
the presence of sodium benzoate, the solubility of benzyl
alcohol in the aqueous phase increases. Due to the presence
of benzyl alcohol and sodium benzoate in the aqueous phase,
some ester is also solubilized in the aqueous phase. Also, it
was found that the dispersion characteristics of the system
changes after about 30% conversion. After 30% conversion
of the ester, the time required for the phases to separate
increased by about 50% over that in the initial stages,
indicating finer and better dispersion of the phases. These
two factors increase the contact between the OH- ions and
the ester, and the reaction proceeds smoothly. When chlo-
robenzyl chloride is treated with sodium benzoate in the
presence of a phase transfer catalyst, there is certain quantity
of [Q+C6H5COO-], [Q+Cl-] left in the organic phase after
complete conversion of substrate is achieved. Experiments
were performed to find out if this catalyst partitioned in the
organic phase can be used to increase the rate of the
hydrolysis reaction. PCBC, OCBC, and DCBC (0.15 mol)
were treated separately with sodium benzoate solution (108
mL, 1.73 M) at 100 °C at 2500 rpm. Tri-n-butylamine (0.003
mol) is used as a catalyst in case of PCBC and DCBC. The
amount of tri-n- butylamine used in case of OCBC was
0.0045 mol. After 7 h of reaction, the reaction mixture was
cooled to room temperature. The aqueous phase was
completely removed, the organic phase was heated to 80 °C,
and hydrolysis was initiated by adding NaOH solution (75
mL, 2.5 M) preheated to 80 °C. The speed of stirring was
2500 rpm. Figure 8 also shows the results of this direct
hydrolysis without purification of the product formed in the
first stage. As can be seen, this strategy increases the rate of
hydrolysis substantially.
The aqueous phase after esterification step [C(aqueous)]
was extracted with dichloroethane, and the organic solvent
was evaporated. The residue was weighed and analysed to
determine the amount of organics present in the aqueous
phase. The aqueous phase left after the hydrolysis step
[E(aqueous)] was also extracted with dichloroethane to
determine the quantity of alcohol present in the aqueous
phase. The results are summarised in Table 3.
Material Balance and Recyclability of the Aqueous
Phase. In the esterification reaction we used 25% molar
excess of sodium benzoate to ensure complete conversion
of the substrate. After completion of the conversion of the
substrate, excess of sodium benzoate remains in the aqueous
phase. This aqueous phase, when acidified, gave benzoic acid
(BA), which was then recovered by filtration of the aqueous
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Vol. 4, No. 1, 2000 / Organic Process Research & Development

Table 3: Material balance for the esterification and
hydrolysis reactions (streams corresponding to Scheme 1)
to neutralize E(aqueous) represented by I(BA) gives the
amount of consumption of benzoic acid required per 0.15
mol of DCBC. In this case, with the net consumption of
0.0045 mol of benzoic acid together with 0.1875 mol sodium
hydroxide (25% excess), DCBC has been converted to 2,4-
dichlorobenzyl alcohol with complete conversion of DCBC
and overall yield of 2,4-dichlorobenzyl alcohols is 97%.
In the conventional one-step process for the manufacture
of benzyl alcohols from corresponding benzyl chlorides, even
small fractions of unreacted benzyl chloride(s) causes
problems in the subsequent separation process. The alkali is
used about 20-25% in excess. The additional problem is
the formation of corresponding dibenzyl ethers. This is
particularly a major problem with chlorobenzyl alcohols as
this represents a substantial yield loss of valuable benzyl
alcohols. The present strategy is clearly beneficial in the
sense that it ensures complete conversion of benzyl chlorides
without involving dibenzyl ethers. This is achieved with
practically the same consumption of alkali and an additional
but nominal consumption of benzoic acid. Even if a small
fraction of benzyl chloride(s) remains unreacted in the
esterification step, it can be easily separated from the ester
by distillation because of the large boiling point difference.
A
B
C
D
E
(organic) (organic) (aqueous) (organic) (aqueous)
moles
moles
moles
moles
moles
PCBC
ester of
PCBC
0.15
-
-
0.14
-
0.0003
-
-
-
-
alcohol of
PCBC
-
0.006
-
0.145
0.001
OCBC
ester of
OCBC
0.15
-
-
0.137
-
-
-
-
-
0.00025
alcohol of
OCBC
-
0.0081
-
0.142
0.003
DCBC
ester of
DCBC
0.15
-
-
0.1467
-
-
-
-
-
0.00029
alcohol of
DCBC
-
-
-
0.1455
0.001
Conclusions
(1) A successful conversion of chlorobenzyl chlorides to
corresponding alcohols via esters has been demonstrated. (2)
The esterification reaction between the chlorobenzyl chlo-
rides and sodium benzoate in the aqueous solutions, follows
pseudo-first-order kinetics for the stirring speed >1000 rpm.
(3) The catalyst used in the esterification reaction also
enhances the hydrolysis reaction leading to the formation of
chlorobenzyl alcohols. (4) The overall yield of chlorobenzyl
alcohols is > 97%. (5) A recycle strategy has been
established wherein the complete recovery of the benzoic
acid after hydrolysis reaction has been eliminated. Because
of this strategy the chlorobenzyl chloride can be successfully
converted into corresponding alcohols via esterification with
just 0.03 mol of benzoic acid per mol of chlorobenzyl alcohol
and 1.25 mol of NaOH per mol of chlorobenzyl alcohol. (6)
The present process does not produce dibenzyl ethers, which
are obtained in the conventional one-step process of convert-
ing benzyl chlorides to benzyl alcohols.
Figure 9. Effect of recycling of the aqueous phase. DCBC )
0. 15 mol. Sodium benzoate ) 108 mL, 1.73 M. Temperature)
100 °C. Catalyst ) Tri-n-butylamine, 0.003 mol. Speed of
stirring ) 2500 rpm.
To establish recyclability of the aqueous phase, the
aqueous phase [E(aqueous)] of 2,4-dichlorobenzyl alcohol
was extracted with dichloroethane. The aqueous layer after
separating dichloroethane phase was heated to boil off traces
of dissolved dichloroethane. Benzoic acid was added to this
aqueous phase to neutralize excess NaOH, and the volume
was adjusted to 108 mL. This was used for esterification of
0.15 mol of DCBC. The conversion profile of DCBC with
this recycled aqueous phase is plotted in Figure 9 with that
using fresh aqueous phase. Both the profiles match exactly.
The difference between benzoic acid recovered [H(BA)]
after acidification of C(aqueous) and the amount required
Acknowledgment
The authors are thankful to M/s Benzo Chem Industries
Pvt. Ltd. (Mumbai, India) for supplying 2-chlorobenzyl
chloride, 4-chlorobenzyl chloride, 2,4-dichlorobenzyl chlo-
ride, and authentic samples of 2-chlorobenzyl alcohol,
4-chlorobenzyl alcohol and 2,4-dichlorobenzyl alcohol.
Received for review June 15, 1999.
OP9900535
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