Process development aspects of production of dibenzyl ether

Article abstract of DOI:10.1021/op980042w

To develop an economically viable process for the synthesis of dibenzyl ether, the reaction of benzyl chloride with aqueous sodium hydroxide in the presence of phase-transfer catalysts has been investigated. The effects of agitation speed, catalyst type and concentration, reaction temperature, mole ratio of reactants, concentration of aqueous sodium hydroxide on the conversion of benzyl chloride, and yield of dibenzyl ether have been evaluated. Tributylamine is found to be a suitable catalyst The reaction is favored by high molar ratio of sodium hydroxide to benzyl chloride. Conversion of benzyl chloride to benzyl alcohol is found to be the rate-controlling step at high sodium hydroxide concentration. Deprotonation of benzyl alcohol at the interphase by aqueous sodium hydroxide is a key step in the formation of dibenzyl ether. The yield of dibenzyl ether is dependent on the concentration of sodium hydroxide in the aqueous phase, the yield being almost 100% at high concentrations of sodium hydroxide. The successful recycle of excess NaOH in the aqueous phase in subsequent batches, without affecting the progress of the reaction, has been demonstrated.

Full text of DOI:10.1021/op980042w

Organic Process Research & Development 1999, 3, 17−27
Process Development Aspects of Production of Dibenzyl Ether
S. R. Joshi, S. B. Sawant,* and J. B. Joshi
Department of Chemical Technology, UniVersity of Mumbai, Matunga, Mumbai 400 019, India
Abstract:
noted that in the commercial process for benzyl alcohol from
To develop an economically viable process for the synthesis of
dibenzyl ether, the reaction of benzyl chloride with aqueous
sodium hydroxide in the presence of phase-transfer catalysts
has been investigated. The effects of agitation speed, catalyst
type and concentration, reaction temperature, mole ratio of
reactants, concentration of aqueous sodium hydroxide on the
conversion of benzyl chloride, and yield of dibenzyl ether have
been evaluated. Tributylamine is found to be a suitable catalyst.
The reaction is favored by high molar ratio of sodium hydroxide
to benzyl chloride. Conversion of benzyl chloride to benzyl
alcohol is found to be the rate-controlling step at high sodium
hydroxide concentration. Deprotonation of benzyl alcohol at
the interphase by aqueous sodium hydroxide is a key step in
the formation of dibenzyl ether. The yield of dibenzyl ether is
dependent on the concentration of sodium hydroxide in the
aqueous phase, the yield being almost 100% at high concentra-
tions of sodium hydroxide. The successful recycle of excess
NaOH in the aqueous phase in subsequent batches, without
affecting the progress of the reaction, has been demonstrated.
benzyl chloride about 20% excess (over stoichiometric
requirement) of soda ash or caustic soda is used, generating
a corresponding excess of inorganic salts. In addition to this,
benzyl alcohol has reasonable solubility in the aqueous phase
and hence dissolved benzyl alcohol is recovered either by
salting out or by extraction and this adds one more step in
1
1
the benzyl alcohol manufacture. Route 1 indicates that
dibenzyl ether can be made in a single-pot reaction directly
from benzyl chloride. The literature indicates use of
trialkylamines as catalysts for synthesizing dibenzyl ether
from benzyl chloride and aqueous sodium hydroxide.4
Therefore, it was decided to study the reaction of benzyl
chloride with aqueous sodium hydroxide in the presence of
phase-transfer catalysts, with the aim that the system can be
further modified for the synthesis of substituted dibenzyl
ethers from substituted benzyl chlorides. The effects of
stirring speed, different catalysts, temperature, the mole ratio
of reactants, the concentration of aqueous phase, the catalyst
and cocatalyst concentration on the conversion of benzyl
chloride, and yield of dibenzyl ether were investigated in
the present work.
1. Introduction
1
.1. Mechanism and Factors Governing Progress of
Dibenzyl ether is used as a plasticizer in the surface
Reaction. The following mechanism gives the formation
coating industry, for special purposes in rubber and textile
industries, and as a solvent for artificial musk and other
odourants. There are many routes for the synthesis of
dibenzyl ether. The most conventional amongst them is
Wiliamson’s synthesis, the reaction of benzyl chloride with
sodium benzylate (NaOCH Ph). The other routes can be
2
broadly classified into five categories, viz.: (1) from benzyl
chloride and an alkali using a phase-transfer catalyst
of dibenzyl ether from benzyl chloride when a trialkylamine
(
NR
3
) is used as a phase-transfer catalyst. Let us represent
+
+
(C
6
H
5
)CH
2
- by Bn, and BnN R
3
by Q :
+
-
BnCl
+ R N h
[Q Cl ]
3
benzyl chloride
quaternary ammonium chloride
organic phase) (1)
In the first step, quaternerisation of the tertiary amine takes
(
1
-4
5
(
PTC), (2) by dehydration of benzyl alcohol, (3) by the
6
,7
reaction of benzyl chloride with benzyl alcohol, (4) by
reduction of benzaldehyde, and (5) via electrochemical
methods.10 Routes 2 and 3 need benzyl alcohol. It may be
place in the organic phase. This quaternary ammonium salt
actually acts as the phase-transfer catalyst.
8,9
+
-
-
+
-
-
[
Q Cl ] + OH h [Q OH ] + Cl
org aq org aq
*
To whom correspondence should be addressed. E-mail: sbs@udct.
ernet.in. Fax: 91-22-414 5614. Phone: 91-22-414 5616.
(both phases) (2)
(
(
(
(
1) Babayan, A. T.; Torosyan, G. O.; Paravyan, S. L. U.S.S.R. SU 1035020,
1
983; Chem. Abstr. 1984, 100, P22402t.
-
In the second step, extraction of OH ions into the organic
phase takes place.
2) Kodamari, M.; Sawamura, M.; Kubo, N.; Yoshitomi, S. Nippon Kagaku
Kaishi 1980, 1, 58; Chem. Abstr. 1980, 92, 180760d.
3) Mori K.; Yukitake, K.; Matsui, S. Japan Kokai 75 35,123, 1975; Chem.
Abstr. 1975, 83, P96715z.
+
-
+
-
[Q OH ] + BnCl f
BnOH
+ [Q Cl ]
org
org
4) Hwu, D., W.; Hwang, C.; Shih Y.; Chao, C. Ind. Eng. Chem. Res. 1992,
benzyl alcohol
3
1, 177.
(
(
(
(
(
5) Bartok, M. Acta UniV. Szeged. Acta Phys. Chem. 1961, 7, 112.
6) Yamashita, M.; Takegami, Y. Synthesis 1977, 11, 803.
7) Onaka, M.; Kawai, M.; Izumi, Y. Chem. Lett. 1983, 7, 1101.
8) Kikugawa, Y. Chem. Lett. 1979, 4, 415.
(
organic phase) (3)
In the third step, benzyl alcohol is formed by the reaction
of extracted OH with benzyl chloride. There are two
possible ways by which the benzyl alcohol formed can react:
-
9) Kato, J.; Iwasawa, N.; Mukaiyama, T. Chem. Lett. 1985, 6, 743.
(
10) Torii, S.; Takagishi, S.; Inokuchi, T. Bull. Chem. Soc. Jpn. 1987, 60 (2),
7
75-776.
(
11) Ullmann’s Encyclopedia of Industrial Chemistry, 5th ed.; VCH Verlags-
+
-
+
-
BnOHorg + [Q OH ] h [Q OBn ] + H O (4a)
gesellschaft mbH: Weinheim, 1985; Vol. A4.
org
org
2
1
0.1021/op980042w CCC: $18.00 © 1999 American Chemical Society and Royal Society of Chemistry
Vol. 3, No. 1, 1999 / Organic Process Research & Development
•
17
Published on Web 11/20/1998

-
Benzyl alcohol can react with extracted OH to give
+
-
[
Q OBn ] in the organic phase. Benzyl alcohol can also
+
-
produce [Q OBn ] in the organic phase by an interfacial
mechanism, which comprises the following two steps:
1
2,13
BnOHorg + Na + OH h Na+
+
-
+
aq
aq
anchored to interface
OBn-
+ H O (4b-1)
2
anchored to interface
Benzyl alcohol gets deprotonated at the phase boundary. The
-
anion OBn remains anchored at the interphase but in the
organic phase, and similarly Na+ gets anchored to the
interphase but in the aqueous phase, a sort of bilayer
arrangement in the absence of a phase-transfer catalyst.
OBn-
+ [Q Cl ] h [Q OBn ] + Cl
org org aq
+
-
+
-
-
anchored to interface
(both phases) (4b-2)
The anchored anion is carried to the interior of the organic
phase-by the phase transfer catalyst.
Figure 1. Effect of speed of stirring. Moles of benzyl chloride
) 0.3. Moles of tributylamine ) 0.003. NaOH solution ) 11.5
M, 160 mL. Temperature ) 80 °C.
+
-
+
-
[
Q OBn ] + BnCl f [Q Cl ] +
BnOBn
dibenzyl ether
(
organic phase) (5)
It has been reported that degradation of benzyltriethyl-
ammonium chloride in the presence of strong alkali (50%
NaOH) produces benzyldiethylamine (80%), triethylamine
-
OBn , which is carried to the organic phase, reacts with
benzyl chloride irreversibly to give dibenzyl ether.
The following factors affect the progress of the reaction.
1) Nature of anion to be extracted: It is difficult to extract
OH ion into the organic phase because of its low polariz-
1
8
(6%), and dibenzyl ether (3%).
This eliminates the
possibility of reaction 6 being the major route for the
degradation of catalyst, and the catalyst is lost mainly due
to the Hoffman elimination reaction. As the concentration
of NaOH increases, the rate of decomposition of the catalyst
(
-
-
-
ibility. OBn is much more lipophilic compared to OH
and is, therefore, extracted very easily into the organic
1
7
increases.
.2. Kinetics. When transfer of anions to the organic
phase.14
1
(
2) Effect of change in NaOH concentration: This has a
two-fold effect on the overall reaction, as explained below.
a) As the concentration of NaOH decreases, more OH
is transferred to the organic phase in the form of [Q OH ]‚
phase follows the extraction mechanism, we observe a first-
order dependence of the rate of reaction on both the substrate
-
(
1
3,14,19
concentration and the catalyst concentration.
In such
+
-
cases, a plot of -ln(1 - x) versus time is a straight line,
where x is the fractional conversion of the substrate, defined
as
nH
2
sel
O. Landini et al. reported a 45 times increase in the
OH/Cl value when the NaOH concentration was changed
K
15
sel
from 50% to 15% (w/w). The K Cl/OH value reported by
sel
16
de la Zerda et al. is 950, and that of K BnO/OH is 1900.
moles of the substrate consumed
x )
(
b) As the concentration of NaOH increases, fewer water
molecules are transferred per OH ion (as [Q OH ]‚nH
moles of the substrate charged
-
+
-
2
O).
Hydroxyl ions, which are less hydrated, are more reactive,
and hence as the concentration of NaOH increases the
The slope of the line gives the observed pseudo-first-order
rate constant, k . Also, a plot ln k versus ln C is a
obs
obs
0
-
15,17
reactivity of transferred OH increases.
3) Degradation of the catalyst: There are two possible
reactions by which the catalyst is degraded. A catalyst such
straight line, where C is the initial concentration of the
0
(
catalyst.
+
-
3
as [BnN Et OH ] may undergo the following reactions:
2
. Experimental Section
.1. Method. All the experiments were carried out in a
2
+
-
[
BnN Et OH ] h BnOH + Et N
(6)
3
3
batch manner. A borosillicate glass reactor of 400-mL
capacity, provided with a stirrer and baffles, was used. A
constant-temperature bath was used for maintaining the
desired temperature.
+
-
[
BnN Et OH ] f BnNEt + H CdCH + H O
3 2 2 2 2
(Hoffman elimination) (7)
(
12) Makosza, M. Pure Appl. Chem. 1975, 43, 439.
(15) Landini, D.; Maia, A.; Rampoldi, A. J. Org. Chem. 1986, 51, 5475.
(16) de la Zerda, J.; Sasson, Y. J. Chem. Soc., Perkin Trans. 2 1987, 1147.
(17) Landini, D.; Maia, A. J. Chem. Soc., Chem. Commun. 1984, 1041.
(18) Landini, D.; Maia, A.; Rampoldi, A. J. Org. Chem. 1986, 51, 3187.
(19) Rabinovitz, M.; Cohen, Y.; Halpern, M. Angew. Chem., Int. Ed. Engl. 1986,
25, 960.
(13) Dehmlow, E. V.; Dehmlow S. S. Phase Transfer Catalysis, 3rd ed.; VCH
Verlagsgesellschaft mbH: Weinheim, 1993.
(
14) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase Transfer Catalysis:
Fundamentals, Applications & Industrial PerspectiVes; Chapman & Hall,
Inc.: New York, 1994.
18
•
Vol. 3, No. 1, 1999 / Organic Process Research & Development

A predetermined quantity of aqueous sodium hydroxide
was added to the reactor. The temperature of the bath was
raised to the predetermined value and maintained there. The
measured quantity of benzyl chloride preheated to the
required temperature was then added, followed immediately
by a known quantity of the catalyst, and the run was started.
Very small quantities of samples were withdrawn at prede-
termined time intervals, and the organic phase was analyzed
by gas chromatography for the conversion of BnCl and the
yield of dibenzyl ether. The effect of impeller speed was
also investigated.
2.2. Analysis. The organic phase was analyzed by gas
chromatography using a 2-m 10% OV-17 column. Nitrogen
was the carrier, and detector was FID. Other parameters
were as follows:
injection temperature
detector temperature
nitrogen flow rate
350 °C
325 °C
30 mL/min
110 °C for 5 min, 110 °C f
temperature programming
275 °C at 30 °C/min,
275 °C maintained for 2 min
Figure 2. Effect of different catalysts on the conversion of
BnCl. Moles of benzyl chloride ) 0.3. Moles of PTC ) 0.00075.
NaOH solution ) 11.5 M, 160 mL. Temperature ) 80 °C. Speed
of stirring ) 2500 rpm.
3
. Results and Discussion
The terms conversion and yield have been defined as
follows:
as a catalyst. Here, 160 mL of 11.5 M sodium hydroxide
and 0.3 mol of benzyl chloride were taken. The molar
catalyst loading was 1% of the organic phase. Figure 1
shows the effect of impeller speed on kobs. It can be seen
that the value of kobs does not increase beyond 2000 rpm,
and the reaction becomes intrinsic reaction rate controlled.
Once the progress of the reaction is controlled by the
intrinsic reaction, the rate of mass transfer is considerably
higher than the intrinsic reaction rate. At very high agitation
speeds (i.e., intrinsic reaction-controlled conditions), we have
observed that the rate of consumption of benzyl chloride is
moles of BnCl consumed
× 100
moles of BnCl charged
%
conversion of BnCl )
%
yield of DBE )
moles of BnCl consumed for the formation of DBE
moles of BnCl consumed
×
100
The effects of the following variables on the conversion
of BnCl and the yield of dibenzyl ether were studied: (1)
stirring speed, (2) catalyst, (3) catalyst and cocatalyst loading,
+
+
(
4) temperature, (5) concentration of aqueous sodium hy-
droxide, and (6) volume of the aqueous phase.
.1. Effect of Change in the Stirring Speed. A phase-
3 3
higher with Bu N Bn than that obtained with Et N Bn
(Figure 2). Further, since the progress is intrinsic reaction
3
controlled, the mass-transfer rate is higher than the intrinsic
+
transfer-catalysed reaction is said to be mass-transfer rate-
limited when the rate of anion transfer across the interface
is slower than the rate of intrinsic reaction. The phase-
transfer-catalysed reaction is said to be intrinsic reaction rate-
limited 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.
reaction rate (with Bu
3
N Bn), which obviously means that
at the same speed of agitation the mass-transfer rate would
be considerably higher than the intrinsic reaction rate with
+
Et
3
N Bn, and hence no mass-transfer limitation would exist
in this case. All the subsequent experiments were performed
at 2500 rpm.
3.2. Effect of Catalyst. Experiments were carried out
at 80 °C with different catalysts. The catalysts used were
triethylamine, tri-n-butylamine, and trioctylamine. Molar
loading of all the catalysts was 0.25% of organic phase.
Again, 0.3 mol of benzyl chloride and 160 mL of 11.5 M
sodium hydroxide were used. The results are shown in
Figure 2.
When dibenzyl ether is synthesised by treating benzyl
chloride with aqueous alkali in the presence of tertiary amine
as catalyst, the kinetics of the overall reaction can be
described by a first-order model based on the concentration
of benzyl chloride in the organic phase after an induction
period.4 We have also found a first-order dependence of
the reaction on the benzyl chloride concentration in the
organic phase. To study the effect of the speed of stirring,
experiments were performed at 80 °C using tri-n-butylamine
As can be seen from the figure, tri-n-butylamine and
trioctylamine have comparable catalytic activities in the
initial period, and both in turn are more active than
triethylamine. However, tri-n-butylamine gives higher con-
version in the later period of the reaction as compared to
trioctylamine. It has been demonstrated that, as the lipophilic
-
nature of the quat increases, extractability of OH into the
20
+
-
organic phase increases. Therefore, the [Q OH ] concen-
tration in the organic phase is expected to be higher for tri-
Vol. 3, No. 1, 1999 / Organic Process Research & Development
•
19

Figure 3. Effect of catalyst concentration on the conversion
of BnCl. Moles of benzyl chloride ) 0.3. PTC ) triethylamine.
Moles of NaOH ) 0.4. NaOH solution ) 11.5 M. Temperature
Figure 5. Effect of the catalyst concentration. Moles of benzyl
chloride ) 0.3. PTC ) triethylamine. NaOH solution ) 11.5
M, 160 mL. Temperature ) 80 °C. Speed of stirring ) 2500
rpm.
)
80 °C. Speed of stirring ) 2500 rpm.
Figure 6. Effect of the stepwise addition of the catalyst on the
conversion of BnCl. Moles of benzyl chloride ) 0.3. PTC )
triethylamine. Single addition ) 0.006 mol of triethylamine. In-
lot addition ) 0.0015 mol of triethylamine at 0, 120, 240, and
Figure 4. Effect of the catalyst concentration on the conversion
of BnCl. Moles of benzyl chloride ) 0.3. PTC ) triethylamine.
NaOH solution ) 11.5 M, 160 mL. Temperature ) 80 °C. Speed
of stirring ) 2500 rpm.
3
60 min. NaOH solution ) 11.5 M, 160 mL. Temperature )
0 °C. Speed of stirring ) 2500 rpm.
8
n-butylamine and trioctylamine than that for triethylamine.
+
-
to be the rate-determining step. Results presented in the
subsequent sections have been used to justify the same.
As the [Q OH ] concentration in the organic phase increases,
benzyl chloride is consumed (reaction 3) at a faster rate, and
the rate of overall reaction increases. Similar results have
3
.3. Effect of Catalyst and Cocatalyst Loading. The
4
effect of the catalyst loading was investigated for two
different mole ratios of reactants. Figure 3 shows the effect
of the catalyst loading for a benzyl chloride-to-sodium
hydroxide mole ratio of 3:4, and Figure 4 shows that for the
mole ratio of 3:18.3.
As can be seen from both figures, the conversion of BnCl
increases as the catalyst loading increases. For the data in
Figure 4, we determined the pseudo-first-order rate constant
corresponding to different catalyst concentrations. Only the
been reported for the synthesis of dibenzyl ether. The effect
of increasing hydrophobicity of the quaternary ion seems to
level off after tri-n-butylamine. In all the above experiments,
the yield of dibenzyl ether was almost 100% throughout the
reaction. This indicates that the intrinsic reaction 3, involving
+
-
[
Q OH ] leading to the formation of benzyl alcohol, is
influenced by the type of the catalyst used and hence is likely
(20) Herriott A. W.; Picker, D. J. Am. Chem. Soc. 1975, 97, 2345.
20
•
Vol. 3, No. 1, 1999 / Organic Process Research & Development

Figure 7. Effect of cocatalyst concentration on the conversion
of BnCl. Moles of benzyl chloride ) 0.3. PTC ) triethylamine,
Figure 9. Arrhenius plot. Moles of benzyl chloride ) 0.3. Moles
of tributylamine ) 0.003. NaOH solution ) 11.5 M, 160 mL.
Speed of stirring ) 2500 rpm.
0
.006 mol. Cocatalyst ) potassium iodide. Moles of NaOH )
.4. NaOH solution ) 11.5 M. Temperature ) 80 °C. Speed of
0
stirring ) 2500 rpm.
Figure 10. Effect of change in NaOH concentration at constant
aqueous phase volume on the conversion of BnCl. Moles of
benzyl chloride ) 0.3. Moles of triethylamine ) 0.006. NaOH
solution ) 160 mL. Temperature ) 80 °C. Speed of stirring )
Figure 8. Kinetics plotsfirst-order dependence. Moles of
benzyl chloride ) 0.3. Moles of tributylamine ) 0.003. NaOH
solution ) 11.5 M, 160 mL. Speed of stirring ) 2500 rpm.
2500 rpm.
Potassium iodide acts as a cocatalyst for many phase-
initial data points were considered, as the value of kobs drops
with time due to catalyst degradation at higher temperatures.
transfer catalysis reactions. Figure 7 shows the effect of
potassium iodide concentration on the progress of the reaction
when the benzyl chloride-to-NaOH mole ratio is 3:4.
Increasing the concentration of potassium iodide increases
the rate of the reaction. Because of the large ionic radius
0
A plot of ln kobs vs ln C was made (Figure 5). This gave a
straight line whose slope was unity. This type of trend is
19
characteristic of an extraction mechanism. This indicates
-
-
that the OH ions are extracted into the organic phase.
and greater polarizability of the I ion, it is a good
We also attempted in-lot addition of catalyst at different
intervals. Figure 6 shows the comparison of addition of 2%
triethylamine in a single stage and addition of 0.5% triethyl-
amine in four steps of 2 h. It can be seen from Figure 6
that the latter strategy reduces neither the batch time nor the
catalyst requirement.
nucleophile as well as a good leaving group. When KI is
used along with triethylamine, the rate of benzyl chloride
consumption increases with an increase in the concentration
of KI. I gets transferred to the organic phase through PTC
and forms benzyl iodide, which is more reactive than benzyl
chloride and hence increases the rate of formation of benzyl
-
Vol. 3, No. 1, 1999 / Organic Process Research & Development
•
21

Figure 11. Effect of change in NaOH concentration at constant
aqueous phase volume on the yield of dibenzyl ether (DBE).
Moles of benzyl chloride ) 0.3. Moles of triethylamine ) 0.006.
NaOH solution ) 160 mL. Temperature ) 80 °C. Speed of
stirring ) 2500 rpm.
Figure 12. Effect of change in the concentration of NaOH,
keeping the mole ratio constant, on the conversion of BnCl.
Moles of benzyl chloride ) 0.3. Moles of triethylamine ) 0.006.
Moles of NaOH ) 0.4. Temperature ) 80 °C. Speed of stirring
)
2500 rpm.
alcohol together with that of the overall reaction. Similar
4
results have been reported by Hwu et al. for the synthesis
of dibenzyl ether from benzyl chloride. This also supports
the earlier observation in section 3.2 that the intrinsic reaction
(reaction 3) is the rate-influencing step. From Figures 3 and
7, it is seen that, though the addition of KI increases the
rate of conversion of benzyl chloride, increasing the catalyst
concentration is a better proposition, as the cost of KI is
considerably higher than that of triethylamine. Hence,
further studies were carried out in the absence of KI.
3.4. Effect of Temperature. Figure 8 shows the effect
of temperature for the case of tri-n-butylamine as a catalyst.
The experiments were carried out using 160 mL of 11.5 M
aqueous sodium hydroxide solution, 0.3 mol of benzyl
chloride, and 0.003 mol of tri-n-butylamine as catalyst.
Figure 8 also shows the pseudo-first-order kinetics of the
reaction under consideration. We notice that at higher
temperature the value of kobs drops gradually. It can also be
seen from Figure 8 that the rate of reaction does not increase
appreciably when temperature changes from 90 to 100 °C.
This may be because of the higher rate of degradation of
catalyst due to Hoffman elimination. The Arrhenius plot
was made (Figure 9). The energy of activation was found
to be 13.14 kcal/gmol. This high value also confirms the
absence of mass-transfer resistance, and the progress of the
reaction is governed by the intrinsic reaction. In all the above
experiments, the yield of dibenzyl ether is almost 100%
throughout the reaction.
Figure 13. Effect of change in the concentration of NaOH,
keeping the mole ratio constant, on the yield of dibenzyl ether
(
DBE). Moles of benzyl chloride ) 0.3. Moles of triethylamine
0.006. Moles of NaOH ) 0.4. Temperature ) 80 °C. Speed
of stirring ) 2500 rpm.
)
3
.5.1. Effect of NaOH Concentration, Keeping Vol-
ume of Aqueous Phase Constant. When the concentration
of aqueous sodium hydroxide is increased, keeping the
volume constant, the mole ratio of benzyl chloride to sodium
hydroxide increases with increasing concentration. The
effects of changes in the concentration of aqueous NaOH
on the conversion of BnCl and the yield of dibenzyl ether
are shown in Figures 10 and 11, respectively.
3
.5. Effect of Concentration of Aqueous Sodium
Hydroxide. The effect of concentration of aqueous phase
was studied in two ways: (1) by changing sodium hydroxide
concentration at a constant volume of the aqueous phase and
(2) by changing aqueous sodium hydroxide concentration
at a constant mole ratio of reactants. The experiments were
conducted at 80 °C with 2% triethylamine as a catalyst.
3.5.2. Effect of NaOH Concentration, Keeping Mole
Ratio of Reactants Constant. The initial concentration of
22
•
Vol. 3, No. 1, 1999 / Organic Process Research & Development

Figure 15. Progress of the reaction between benzyl chloride
and benzyl alcohol (experiment A). Moles of benzyl chloride )
Figure 14. Effect of NaOH concentration on the progress of
the reaction between benzyl chloride and benzyl alcohol.
0
0
.15. Moles of benzyl alcohol ) 0.15. Moles of triethylamine )
.006. NaOH solution ) 11.5 M, 160 mL. Temperature ) 80
aqueous phase was varied, keeping the mole ratio of benzyl
chloride to sodium hydroxide constant, viz. 3:4. It may be
noted that, with an increase in sodium hydroxide concentra-
tion, the volume of the aqueous phase decreases, and vice
versa. The effect of NaOH concentration on the conversion
of BnCl and the yield of dibenzyl ether is shown in Figures
°
C. Speed of stirring ) 2500 rpm.
12 and 13, respectively.
From Figures 11 and 13, it is clear that the yield of
dibenzyl ether is a function of NaOH concentration. Changes
in the catalyst, the temperature, and the catalyst and
cocatalyst concentrations had practically no effect on the
yield of dibenzyl ether. With increasing concentration of
NaOH, deprotonation of benzyl alcohol increases (reaction
+
-
4
b-1). Further, more [Q OBn ] is formed in the organic
phase (reaction 4b-2), which reacts with benzyl chloride
reaction 5) to give dibenzyl ether, thereby improving its
yield.
To determine the rate-limiting step in the said mechanism,
we performed the following experiments.
A) A mixture of 0.15 mol of benzyl chloride and 0.15
(
(
mol of benzyl alcohol was reacted with 160 mL of 11.5 M
NaOH at 80 °C in the presence of 0.006 mol of triethylamine
at 2500 rpm.
Figure 16. Progress of the reaction between benzyl chloride
and benzyl alcohol (experiment B). Moles of benzyl chloride )
0
0
.15. Moles of benzyl alcohol ) 0.15. Moles of triethylamine )
.006. NaOH solution ) 2.5 M, 160 mL. Temperature ) 80
(B) Another mixture of 0.15 mol of benzyl chloride and
0.15 mol of benzyl alcohol was reacted with 160 mL of 2.5
°C. Speed of stirring ) 2500 rpm.
M NaOH at 80 °C in the presence of 0.006 mol of
triethylamine at 2500 rpm.
benzyl chloride and benzyl alcohol react rather rapidly. From
a similar plot (Figure 16) for experiment B, we observe that
though concentration of benzyl chloride decreases, the
concentration of benzyl alcohol does not decrease cor-
respondingly but reaches a limiting value. In experiment
B, benzyl alcohol gets deprotonated to a lesser extent due
to the lower NaOH concentration. Therefore, the formation
of dibenzyl ether takes place at a slower rate. Benzyl
chloride is consumed by two reactions, first for the formation
of benzyl alcohol (reaction 3) and then for the formation of
dibenzyl ether (reaction 5). When the rate of consumption
Figure 14 shows the conversion profile for both experi-
ments. The figure also shows the results of the experiment
in which only 0.3 mol of benzyl chloride is used, the other
conditions being same as those of experiment B. In the first
case, when the concentration of NaOH is 11.5 M, 95%
conversion of BnCl takes place in less than 10 min. When
the concentrations of benzyl chloride and benzyl alcohol are
plotted against time (Figure 15) for experiment A, we observe
that both are consumed at the same rate. This shows that,
in the presence of the catalyst and highly concentrated NaOH,
Vol. 3, No. 1, 1999 / Organic Process Research & Development
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23

Figure 18. Effect of the change in NaOH concentration at
constant aqueous phase volume on the conversion to BnOH.
Moles of benzyl chloride ) 0.3. Moles of triethylamine ) 0.006.
NaOH solution ) 160 mL. Temperature ) 80 °C. Speed of
stirring ) 2500 rpm.
Figure 17. Effect of the change in the volume of aqueous phase
on the conversion of BnCl. Moles of benzyl chloride ) 0.3.
Moles of triethylamine ) 0.006. NaOH solution ) 11.5 M.
Temperature ) 80 °C. Speed of stirring ) 2500 rpm.
of benzyl alcohol for the formation of dibenzyl ether equals
the rate of formation of benzyl alcohol from benzyl chloride,
the concentration of benzyl alcohol remains constant, and
the concentration of benzyl chloride decreases. It is very
clear from the discussion that, at high NaOH concentration,
conversion of benzyl chloride to benzyl alcohol is the rate-
limiting step.
regarding both steps. The relative rates of both steps decide
the overall conversion profiles as given in Figures 10 and
1
2. The information regarding the first step for each
experiment cannot be obtained directly from Figures 10 and
2. Therefore, we separately plotted conversion to benzyl
1
alcohol versus time for experiments in Figures 10 and 12.
The results are presented in Figures 18 and 19. Conversion
to benzyl alcohol was calculated by using the following
formula:
3.5.3. Effect of Volume of the Aqueous Phase. Here,
0.3 mol of benzyl chloride was treated with different volumes
of 11.5 M NaOH solutions in the presence of 0.006 mol of
triethylamine at 80 °C and 2500 rpm. The volume of
aqueous phase was increased from 35 to 160 mL. Figure
%
conversion to BnOH )
moles of BnOH observed + moles of dibenzyl ether formed
moles of BnCl taken initially
17 shows the effect of the aqueous phase volume on the
×
100
conversion of BnCl. As the volume of aqueous phase
increases, the organic phase gets completely dispersed in the
aqueous phase. Here, the aqueous phase is the continuous
phase, and more area is made available for mass transfer.
As we go on increasing the aqueous phase volume, the
interfacial area increases until complete dispersion of the
organic phase has occurred and further increases in the
aqueous phase volume will not increase the interfacial area
for mass transfer to take place. This levels off the effect of
the aqueous phase volume. This is confirmed by the results
in Figure 17. There is a noticeable increase in the rate of
reaction when the volume of aqueous phase increases from
Conversion to benzyl alcohol refers to the consumption of
benzyl chloride by reaction 3 alone.
As can be seen from Figure 18, the conversion to benzyl
alcohol is dependent on the aqueous phase concentration.
In 2.5 M NaOH solution, the amount of OH extracted to
the organic phase is higher, but it is highly hydrated and
-
15,17
less reactive.
As the concentration of aqueous phase
-
increases, the amount of OH extracted decreases, but the
extracted OH is more reactive.
in our set of experiments is maximum when 11.5 M NaOH
is used. In the case of 11.5 M NaOH, the amount of OH
extracted to the organic phase is much less than that in 2.5
M NaOH. But because of the high reactivity of extracted
OH , the conversion to BnOH is the same initially for 2.5
-
15,17
-
The reactivity of OH
-
35 to 70 mL but no appreciable change when the aqueous
phase volume is further increased to 160 mL.
-
We can broadly divide the mechanism in two steps, viz.:
(
1) formation of benzyl alcohol and (2) reaction of benzyl
and 11.5 M NaOH. Also, we observe that the rate of
conversion to BnOH drops significantly after some time in
the case of 11.5 M NaOH. This is because of degradation
of catalyst due to the higher concentration of NaOH. For
2.5 M NaOH, the degradation of catalyst is minimal because
the concentration of aqueous phase decreases sharply with
the progress of the reaction.
alcohol with benzyl chloride to give dibenzyl ether. Benzyl
chloride is consumed in the first step for the formation of
benzyl alcohol according to reaction 3 and in the second
step for the formation of dibenzyl ether by reaction 5.
Therefore, plots of conversion of benzyl chloride versus time
as shown in Figures 10 and 12 do not give much information
24
•
Vol. 3, No. 1, 1999 / Organic Process Research & Development

decreases considerably with the progress of the reaction, and
hence there is no deactivation of catalyst for concentrated
NaOH solutions.
3
.6. Discussions: Mechanism and the Rate Determin-
1
9
ing Step (RDS). Rabinovitz et al. have given the criteria
for determining whether the anions are transferred to the
organic phase by the extraction mechanism or by the
interfacial mechanism. Accordingly, the following observa-
-
tions in the present study support that the OH is transferred
by the extraction mechanism into the organic phase:
(a) In the initial period of the reaction, the rate of
consumption of benzyl chloride shows a first-order depen-
dence on the concentration of catalyst triethylamine (Figure
5
) and benzyl chloride (Figure 8).
b) The rate also increases with increasing hydrophobisity
of the catalyst (i.e., from triethyl- to tri-n-butylamine).
(
+
-
To understand the formation of [Q OBn ], consider
reactions 4a, 4b-1, and 4b-2. For deprotonation by reaction
4a, formation of [Q OBn ] depends on the activity as well
as the concentration of [Q OH ]. It has been reported that
with an increase in NaOH concentration the extractability
of OH decreases while its activity (decided by hydration
+
-
Figure 19. Effect of change in the concentration of NaOH,
keeping the mole ratio constant, on the conversion to BnOH.
Moles of benzyl chloride ) 0.3. Moles of triethylamine ) 0.006.
Moles of NaOH ) 0.4. Temperature ) 80 °C. Speed of stirring
+
-
-
)
2500 rpm.
1
5
state) increases. Thus, the concentration and activity of
+
-
When the concentration of aqueous phase is changed,
[Q OH ] in organic phase are affected in opposite directions
by NaOH concentration. It may be pointed out that the rate
of formation of benzyl alcohol, which depends on the
concentration and activity of [Q OH ], first decreases and
then increases with an increase in the concentration of NaOH
keeping the benzyl chloride-to-sodium hydroxide molar ratio
constant, the volume of aqueous phase changes. In all the
experiments presented in Figure 19, the benzyl chloride-to-
sodium hydroxide molar ratio is 3:4. Therefore, there is a
rather sharp change in the aqueous phase concentration with
progress of reaction. We can clearly conclude that 11.5 M
NaOH solution in this set of experiments (BnCl:NaOH )
+
-
(
Figures 18 and 19). Thus, a monotonic increase in the
+
-
formation of [Q OBn ] according to reaction 4a may not
occur with an increase in the concentration of NaOH.
However, formation of [Q OBn ] will increase continuously
with an increase in the NaOH concentration according to
reaction 4b-1 followed by 4b-2. The increase in concentra-
tion of [Q OBn ] leads to an increased rate of etherification
according to reaction 5. The observed data (Figures 11, 13-
3:4) cannot behave exactly in a manner similar to that in
+
-
the previous case, where the molar ratio of BnCl to NaOH
was 3:18.3. With BnCl:NaOH at 3:18.3, the concentration
of NaOH in the aqueous phase does not change substantially
because of the large stoichiometric excess of NaOH used.
As the initial concentration of aqueous phase increases, the
deviation in the behavior of the aqueous phase from the prior
case increases. In the present set of experiments, as we move
from 2.5 to 11.5 M NaOH, the volume of aqueous phase
decreases. When the initial volume of aqueous phase
+
-
1
6) support this proposed mechanistic step of interfacial
deprotonation of benzyl alcohol.
The following points may be noted regarding the rate-
determining step (RDS):
(1) The initial rate of consumption of benzyl chloride is
-
decreases from 160 to 80 mL, the amount of OH extracted
directly proportional to benzyl chloride concentration (first-
order dependence). This indicates that reaction 1 or 3 or 5
is the RDS.
(2) For quaternisation (reaction 1) to be the RDS, the rates
of reactions with 11.5 and 2.5 M NaOH should have been
the same. However, results in Figure 14 show that sodium
hydroxide concentration has a pronounced effect on the rate
of overall reaction.
decreases as the concentration of aqueous phase increases.
As the concentration of aqueous phase remains relatively
low, there is practically no change in the level of hydration
-
of the extracted OH . The net result is that the rate of
conversion to BnOH decreases. For an aqueous phase
volume of 64 (initial concentration 6.25 M)-34.78 mL
(initial concentration 11.5 M), the effect of change in volume
of the aqueous phase becomes dominant. We therefore
notice that, as the initial concentration of aqueous phase
increases from 2.5 to 6.25 M, the rate of the first step
decreases. But as the concentration of aqueous phase
increases further, the dehydrating effect of NaOH becomes
(3) At very high concentrations of NaOH, the yield of
dibenzyl ether is almost 100% throughout the reaction. This
indicates that the etherification reaction (reaction 5) is very
fast, particularly at high NaOH concentration.
(4) When conversion of benzyl chloride to BnOH is
plotted against time (Figures 18 and 19), the trends observed
match well with the trends observed when conversion of
BnCl for the overall reaction is plotted against time (Figures
-
dominant and more than compensates for low OH extrac-
tion. We therefore see a minimum at around 6.25 M NaOH
solution, and then the rate of conversion to BnOH increases.
In this set of experiments, the aqueous phase concentration
Vol. 3, No. 1, 1999 / Organic Process Research & Development
•
25

1
0 and 12). This is also an indirect proof of benzyl alcohol
formation being the RDS.
5) At low NaOH concentration, there is an appreciable
(
amount of benzyl alcohol in the reaction mixture. Under
these circumstances, it is possible that the rates of reactions
3
and 5 are comparable. This fact can be confirmed from
results presented in Figures 14 and 16. Further, Figure 15
shows that at high NaOH concentration, concentrations of
benzyl chloride and benzyl alcohol are equal at any time
during the reaction. Further, we do not see any excess benzyl
alcohol formation, indicating that the rate of etherification
is very fast compared to the rate of benzyl alcohol formation.
With the concentration of NaOH equal to 2.5 M, benzyl
alcohol concentration reaches a limiting value while benzyl
chloride concentration decreases with time (Figure 16). This
limiting value indicates that the rate of formation of benzyl
alcohol equals the rate of consumption of benzyl alcohol,
which in turn equals the rate of formation of dibenzyl ether.
For the conditions under which the effect of stirring speed,
catalyst, catalyst and cocatalyst loading, temperature are
studied, the rate-determining step, therefore, is given by
reaction 3.
Figure 20. Effect of recycling of the aqueous phase on the
progress of the reaction. Moles of benzyl chloride ) 0.3. Moles
of tributylamine ) 0.003. NaOH solution ) 11.5 M, 160 mL.
Temperature ) 90 °C. Speed of stirring ) 2500 rpm.
Thus, the mechanism based on the results reported here
standard oxalic acid solution. After the sodium hydroxide
concentration was determined accurately, makeup NaOH and
distilled water was added to make 11.5 M NaOH and 160
mL of aqueous phase volume. With this aqueous phase, the
second recycling experiment was performed. Figure 20
shows the results of five such experiments. The only
difference in the aqueous phase of the first experiment and
all recycling experiments is that in the first experiment the
concentration of sodium chloride in the aqueous phase
increases with the progress of the reaction, and in all the
other recycling experiments the aqueous phase remains
saturated with sodium chloride throughout the reaction.
Conversion of BnCl versus time curves of all the experiments
are practically identical. We can, therefore, conclude that
concentration of sodium chloride in the aqueous phase does
not affect the rate of the reaction. Identical conversion
profiles also indicate that the PTC is not recycled with the
aqueous phase. It is either present in the organic phase or
is degraded by the end of the reaction. The net consumption
of NaOH in all the experiments was around 8% more than
the stoichiometric requirements. The alkali was lost mainly
in the separation of sodium chloride formed in the aqueous
phase.
-
consists of extraction of OH into the organic phase. This
-
extracted OH reacts with benzyl chloride to give benzyl
alcohol by reaction 3. This intrinsic nucleophillic substitution
reaction is the rate-determining step at higher sodium
hydroxide concentrations. The benzyl alcohol formed un-
-
dergoes interfacial deprotonation. The OBn anion formed
at the interface is carried to the bulk organic phase by the
PTC, where it reacts with benzyl chloride to give dibenzyl
ether.
3.7. Recycle of Aqueous Phase. For the higher yields
of dibenzyl ether together with high conversion of benzyl
chloride, high concentration and large excess of sodium
hydroxide are necessary. In such cases, after benzyl chloride
is consumed completely, there is still a considerable amount
of sodium hydroxide present in the aqueous phase, which if
recycled reduces the cost of production of dibenzyl ether
considerably. The results of such recycle experiments are
shown in Figure 20. In the first experiment, 0.3 mol of
benzyl chloride was treated with 160 mL of sodium
hydroxide solution of 11.5 M concentration, and 0.003 mol
of tri-n-butylamine was used as a catalyst at 90 °C and 2500
rpm. After 8 h, the reaction was stopped, the reaction
mixture was cooled to room temperature, and both phases
were separated. The amount of NaOH consumed was
calculated and added to the separated aqueous phase, and
the volume was made to 160 mL by adding distilled water.
With this aqueous phase, the first recycling experiment was
performed. This aqueous phase was reacted with 0.3 mol
of benzyl chloride and 0.003 mol of tri-n-butylamine at 90
We have thus demonstrated a single-pot conversion of
benzyl chloride to dibenzyl ether with following features:
(
(
1) almost quantitative conversion of benzyl chloride and
2) almost 100% yield of dibenzyl ether throughout the batch.
4
. Conclusions
°
C and 2500 rpm. After 8 h, the experiment was stopped,
(1) Dibenzyl ether can be prepared by using trialkylamines
and as in the previous case, both phases were separated. The
aqueous phase now contained a considerable amount of
sodium chloride crystals. The clear aqueous phase was
carefully decanted and analysed for sodium hydroxide with
as phase-transfer catalysts in high yields (∼100%) at high
sodium hydroxide concentration (>8.75 M).
(2) At low concentration of sodium hydroxide, the yield
of dibenzyl ether is low.
26
•
Vol. 3, No. 1, 1999 / Organic Process Research & Development

(
3) Conversion of benzyl chloride to benzyl alcohol by
makeup sodium hydroxide without affecting the conversion
of benzyl chloride and the yield of dibenzyl ether.
+
-
action of [Q OH ] in the organic phase is the rate-
determining step at high concentrations of sodium hydroxide.
+
-
(
4) [Q OBn ] is formed in the organic phase by interfacial
deprotonation of benzyl alcohol.
5) Though high excess of sodium hydroxide is used,
unreacted sodium hydroxide can be recycled together with
Received for review May 11, 1998.
OP980042W
(
Vol. 3, No. 1, 1999 / Organic Process Research & Development
•
27