Synthesis of m-phenoxybenzaldehyde starting from chlorobenzene and m-cresol: Some aspects of process development

Article abstract of DOI:10.1021/op990028z

m-Phenoxybenzaldehyde (MPB) is an important intermediate for synthetic pyrethroids. In the present paper, an economic process scheme was developed to synthesize MPB starting from cheaper reactants. The process scheme was started with the synthesis of m-phenoxytoluene (MPT). Oxidation of MPT by air gave MPB, but the selectivity was found to be high at low conversions of about 10%, and if the conversion level was increased, then large amounts of the undesired m-phenoxybenzoic acid (MPBA) was formed. To obtain the desired aldehyde, Rosenmund reduction of MPBA was carried out to give high yields of the MPB. The effects of different parameters such as catalyst, substrate concentration, temperature, etc., were studied for all three of the reactions, viz., Ullmann ether synthesis, oxidation, and Rosenmund reduction. MPT was prepared from chlorobenzene, a relatively cheaper starting material, in the presence of polyethylene glycol) as cosolvent and cuprous chloride as the catalyst. A selectivity of 97% was obtained with 86% conversion to the product. Oxidation of MPT was carried out by air in the presence of cobalt acetate as catalyst and sodium bromide as catalyst promoter. The selectivity with respect to the aldehyde and the ester was 37.4 and 30.6%, respectively, at a restricted overall conversion of 24%. The process parameters were controlled to achieve high selectivity towards the aldehyde. The acid, formed as the side product, was reduced to the aldehyde by Rosenmund reduction via the acyl chloride. At a conversion level of 85%, a selectivity of 87% to MPB was obtained using Pd/C.

Full text of DOI:10.1021/op990028z

Organic Process Research & Development 1999, 3, 416−424
Synthesis of m-Phenoxybenzaldehyde Starting from Chlorobenzene and
m-Cresol: Some Aspects of Process Development
Kavita H. Chandnani and Sampatraj B. Chandalia*
UniVersity Department of Chemical Technology, UniVersity of Mumbai, Matunga (East), Mumbai - 400 019, India
Abstract:
involved it was not an attractive process. The latter method,
air oxidation of MPT, was chosen as it would be a relatively
cheaper method.
m-Phenoxybenzaldehyde (MPB) is an important intermediate
for synthetic pyrethroids. In the present paper, an economic
process scheme was developed to synthesize MPB starting from
cheaper reactants. The process scheme was started with the
synthesis of m-phenoxytoluene (MPT). Oxidation of MPT by
air gave MPB, but the selectivity was found to be high at low
conversions of about 10%, and if the conversion level was
increased, then large amounts of the undesired m-phenoxyben-
zoic acid (MPBA) was formed. To obtain the desired aldehyde,
Rosenmund reduction of MPBA was carried out to give high
yields of the MPB. The effects of different parameters such as
catalyst, substrate concentration, temperature, etc., were studied
for all three of the reactions, Wiz., Ullmann ether synthesis,
oxidation, and Rosenmund reduction. MPT was prepared from
chlorobenzene, a relatively cheaper starting material, in the
presence of poly(ethylene glycol) as cosolvent and cuprous
chloride as the catalyst. A selectivity of 97% was obtained with
86% conversion to the product. Oxidation of MPT was carried
out by air in the presence of cobalt acetate as catalyst and
sodium bromide as catalyst promoter. The selectivity with
respect to the aldehyde and the ester was 37.4 and 30.6%,
respectively, at a restricted overall conversion of 24%. The
process parameters were controlled to achieve high selectivity
towards the aldehyde. The acid, formed as the side product,
was reduced to the aldehyde by Rosenmund reduction via the
acyl chloride. At a conversion level of 85%, a selectivity of 87%
to MPB was obtained using Pd/C.
MPT, the starting material for our process scheme, is
costly; therefore, it was also prepared in an economic way
so as to make over-all, a cheaper process scheme. In the
present work it was found that the yields of oxidation of
MPT to MPB were poor as acid is formed as the byproduct,
aldehyde being more susceptible to oxidation than its toluene
derivative. The acid formed was converted to aldehyde by
Rosenmund reduction. Thus, an attractive process scheme
for the synthesis of MPB can be suggested starting from halo
benzene and m-cresol (Figure 1).
MPT can be synthesized by Ullmann condensation of a
phenolic salt of m-cresol with halobenzene in the presence
of copper salts as catalysts. The chemistry of the Ullmann
reaction is well known as it involves the attack of nucleophile
and results in the cleavage of the carbon-halogen1 bond.
The ease of substitution of the halogen atom decreases1 in
the order I > Br > Cl > F. The condensation is carried out
with copper2,3 or its salts, which serves as the catalyst, by
complexing with the aromatic halide. Generally, reaction
rates are very low due to the overall heterogeneous system;
therefore, organic aprotic solvents3,4 containing heteroatoms
such as N, O, and S, for example, pyridine, quinoline,
diglyme, dimethyl sulfoxide, etc., are employed in the
condensation reaction for dissolving the cuprous chloride and
thus make the system homogeneous. The solvent and the
system must be completely free from water as the coordina-
tion of the hydroxide ion with copper causes depletion of
the true catalytic species.2 The emphasis was on using
chlorobenzene which is relatively cheap and readily available
compared to bromobenzene. Also the possibility of using
any other cosolvent such as PEG instead of other costly
solvents was explored. An attempt was also made to vary
the process conditions so that high selectivities are obtained
at higher conversion levels.
Introduction
m-Phenoxybenzaldehyde (MPB) is an important interme-
diate for the manufacture of synthetic pyrethroids which have
high negative insecticidal activity specially for army worms
and are also herbicidal antidotes for cotton and legumes.
MPB can be prepared by (1) starting from benzaldehydes
the formyl group is protected with aluminum trichloride
followed by bromination. The complex is deprotected with
dilute acid. m-Bromo benzaldehyde is then protected with
ethylene glycol for Ullmann condensation, with a salt of
phenol; by (2) side-chain bromination of m-phenoxytoluene
(MPT), followed by hydrolysis of mixture of benzal/benzyl
halide; or by (3) liquid-phase air oxidation of MPT by air.
In the first method, the protection and then deprotection
increases the number of steps and also the cost of the process.
In the second method, due to the high cost of bromine
For the autoxidation5 of MPT to MPB by air the catalyst
used is reduced during the reaction which is then oxidized
by air in the redox chain system. Lower saturated fatty acids6
such as acetic acid,5,7-9 its anhydrides, or the corresponding
acid10 which is formed as the byproduct itself can be used
as the solvent. The catalysts generally used are cobalt
(1) Harold, W. J. Org. Chem. 1964, 29, 977.
(2) Tuong, T. D.; Hida, M. Bull. Chem. Soc. Jpn. 1971, 44, 765.
(3) Fanta, P. E. Synthesis 1974, 9.
(4) Herbert, K.; Georg, S. Ger. Patent DE 3,040,849, 1982; Chem. Abstr. 97,
162569.
* To whom correspondence should be sent. Address: Dr. S. B. Chandalia,
501, Gulshan -2, Juhu Cross Lane, Andheri (W), Mumbai-400 058, India.
(5) Roger, S.; Jay, K. Metal Catalyzed Oxidations Of Organic Compounds;
Academic Press Inc.: NewYork, 1981.
416
•
Vol. 3, No. 6, 1999 / Organic Process Research & Development
10.1021/op990028z CCC: $18.00 © 1999 American Chemical Society and The Royal Society of Chemistry
Published on Web 11/03/1999

require high temperatures of about 375 °C.14,15 The specific
reduction of m-phenoxybenzoyl chloride to MPB by Rosen-
mund reduction16 with supported Pd was not reported in the
literature. Rosenmund reduction was chosen, as it can be
done even at room temperature instead of at vapor phase as
mentioned by other patentees.
The present paper was an attempt to synthesize MPB,
starting from cheaper reactants so as to make the over-all
process economic and industrially workable. An attempt was
also made to vary the process conditions so that high
selectivities at higher conversions could be obtained from
the viewpoint of process research and development.
Experimental Section
Materials. m-Cresol, chlorobenzene, bromobenzene, po-
tassium hydroxide, toluene, cobalt(II) acetate, copper acetate,
acetic acid, thionyl chloride, N,N-dimethyl formamide (DMF),
PEG-4000 (laboratory grade, from S. D. Fine Chemicals,
India); sodium bromide - analytical grade; cuprous chloride
(prepared in laboratory - cupric chloride, hydrochloric acid
and sodium bisulfite); toluene (used for Rosenmund reduc-
tion): AR grade toluene - dried by refluxing with sodium
metal; Palladium on charcoal - procured from Hindustan
Platinum Ltd. Bombay (Type C-1025/C-III).
1. Synthesis of m-Phenoxytoluene (MPT). Experimen-
tal Setup and Procedure. Predetermined quantities of
m-cresol (8.3 g) and potassium hydroxide (5 g) in 3 mL of
distilled water were taken in a 100 mL capacity, borosilicate
round-bottom flask. The contents were stirred for 0.5 h. A
Dean-Stark apparatus with the condenser was fitted on the
flask, toluene was added to the reaction mixture. The reaction
mixture was azeotropically refluxed for 20 h, to ensure
almost complete removal of water. The solid, potassium
m-cresolate, obtained after distillation of toluene was im-
mediately transferred to the hastelloy autoclave (Parr Instru-
ment Company, U.S.A.) of 100 cm3 capacity. The autoclave
was equipped with a magnetically driven, six-bladed turbine
impeller, electric heater, two baffles, and a cooling coil. The
pressure gauge, pressure release valve, safety head port, and
sampling valve were all situated on the top head. Temper-
ature was measured by a chromium-aluminum thermo-
couple inserted in a thermo-well and regulated by a
temperature indicator controller.
Predetermined quantities of halobenzene and the catalyst
were charged in the autoclave. The reaction temperature was
maintained at (1 °C of the desired value by controlling the
flow rate of cooling water in the internal coil and the heating
rate. Agitation was started. The time of reaction was reckoned
after the desired temperature was attained.
Workup and Isolation of the Product. After the
completion of the reaction, about 800 mL of distilled water
was added to the contents to dissolve the potassium chloride,
which was formed during the reaction. A large amount of
water was added, to avoid any solubility of organic material
in the aqueous medium due to PEG-4000. Dilute sodium
Figure 1. Process scheme for synthses of m-phenoxybenzal-
dehyde. (I) m-Cresol, II chlorobenzene, (III) m-phenoxytoluene,
(IV) m-phenoxybenzoic acid, (V) m-phenoxybenzaldehyde, (VI)
m-phenoxybenzyl acetate.
acetate,7,9 manganese acetate,8 copper acetate,7 etc. Catalyst
activators/promoters such as methyl ethyl ketone or ozone,8
hydrogen bromide,11 sodium bromide,7,12 paraldehyde,12
hydrogen chloride, etc. are used. The temperature and time
of the reaction which are important in deciding the aldehyde
selectivity as given by the patentees are in the range 50-
120 °C6-9,12 and 2.8 min to 56,7 h, respectively.
Patent literature also reports the preparation of MPB from
either m-phenoxybenzoic acid (MPBA) or its esters using
zirconium or its oxide13 containing an element13,14 selected
from Cr, Co, In, Re, Pb, Mn, or Mg. Another patentee has
carried out the hydrogenation over vanadium15 catalysts such
as V2O5 supported on Al2O3, TiO2, or SnO2. These reductions
(6) Imamura, J.; Iwane, Y.; Kobayashi, S.; Onisawa, K. Chem. Abstr. 1977,
88, 104902.
(7) Kamiya, Y.; Ishiyama, K. Sekiyu Gakkaishi 1985, 28 (6), 439-44; Chem.
Abstr. 105, 97087.
(8) Imamura, J.; Takehara, M.; Kizawa, K. Ger. Patent DE 2,605,678, 1976;
Chem. Abstr. 86, 16422.
(9) Imamura, H.; Iwane, Y.; Minagawa, H. JP 78 82,736, 1978; Chem. Abstr.
89, 215068.
(10) Kuckertz, H.; Schaeffer, G. Ger. Patent DE 3,129,194, 1983; Chem. Abstr.
98, 160425.
(11) Agency of Industrial Sciences and Technol. Sanko Chemical Co. Ltd Nippon
Soda Co. Ltd. JP 5850,970, 1983; Chem. Abstr. 100, 174438.
(12) Mitsubishi Petrochemical Co. Ltd. JP 8209,734, 1982; Chem. Abstr. 96,
217471.
(13) Maki, T.; Yokoyama, T. JP 61,1150,43, 1986; Chem. Abstr. 106. 18102.
(14) Yokoyama, T.; Fuji, K. Petrotech (Tokyo) 1991, 14 (7), 633-7 (Jpn); Chem.
Abstr. 116: 105700.
(15) Hargis, D. C., U.S. Patent 4,950,799, 1990; Chem. Abstr. 114, 23418.
Vol. 3, No. 6, 1999 / Organic Process Research & Development
•
417

hydroxide was added to make the reaction mixture alkaline.
The reaction mixture was then filtered to remove the catalyst.
The two layers were then separated. The aqueous layer was
used for analyzing the chloride content. This layer also
contained unreacted m-cresol which was obtained by acidi-
fication of the aqueous layer and then by extraction with
ether, while the organic layer containing the product was
analyzed by gas chromatography.
Analysis. The aqueous layer was analyzed by Volhards
method.17 The amount of the chloride obtained by this
method was corrected for the amount of the catalyst added
as cuprous chloride. The analysis of the organic layer was
done by gas chromatography (GC)(Chemito 8510), using
diphenyl oxide as an internal standard. The GC column and
conditions used were as follows: column used, stainless steel,
3.2 mm i.d. ×2 m; packing, 10% SE-30 on Chromosorb-W;
carrier gas, nitrogen; flow rate, 30 mL/min; detector, FID;
oven temperature, 150 °C; 2 min.; 10 °C/min to 300 °C; 5
min; injector temperature, 300 °C; detector temperature, 300
°C. The amount of m-phenoxytoluene determined by Vol-
hards method matched with that obtained by G. C.
2. Synthesis of m-Phenoxybenzaldehyde (MPB) by Air
Oxidation. Experimental Setup. The reactions were carried
out in a 750 mL capacity, bubble column reactor. The reactor
consisted of a stainless steel tube of 5 cm inside diameter
and 44 cm length. It was provided with an air sparger, a
thermometer pocket, a pressure gauge and a vertical water
condenser. The reactor was heated, when necessary, by use
of a Nichrome heating element wound on the reactor, and
the heat input was controlled by a “Varaic”. With proper
manipulation of heat input, it was possible to maintain the
desired temperature in the reactor within (5 °C. A compres-
sor was used for supplying air. The pressure inside the reactor
and the air flow rate was controlled by means of needle
valves provided at the inlet and the outlet of the reactor. A
calibrated rotameter was provided at the exit to measure the
air flow rate.
Experimental Procedure. Predetermined amounts of the
catalyst and the substrate were mixed with the solvent, and
the solution was shaken thoroughly to make it homogeneous.
The reactor was then kept at the desired temperature, and
the flow of air was started. After the reaction was allowed
to proceed for predetermined period, the reactor was cooled
to room temperature and the pressure was released.
The major products of the reaction were the aldehyde,
the carboxylic acid, and the acetate. The reaction mixture
was filtered and distilled under vacuum to remove solvent.
It was then diluted with water and the organic compound
extracted in toluene. The organic layer was washed with
water for further analysis.
solution was adjusted to 3.0. For measuring the pH, an
electronic pH meter (Chemito) was used. A solution of
hydroxylamine hydrochloride in 90% methanol was made,
and the pH was adjusted to 3.0 separately. Both solutions
were mixed and kept at 45 °C for 1 h.
The liberated HCl was titrated potentiometrically to pH
3.0 using 0.1 N sodium hydroxide solution.
Analysis of Acid Formed in the Reaction. The car-
boxylic acid present in the reaction mixture was analyzed
by diluting a sample with water and extracting with ether.
The combined ether extracts were washed with aqueous
sodium bicarbonate solution to extract the carboxylic acid
as sodium salt. The aqueous layer was neutralized with
mineral acid to precipitate the carboxylic acid. The latter
was dried and weighed. If the acid formed was low, then
the ether extract after washing with water was titrated with
standard methanolic sodium hydroxide to estimate the
carboxylic acid.
Analysis of Ester and unreacetd m-Phenoxytoluene.
m-Phenoxybenzyl acetate, and unreacted MPT were analyzed
by gas chromatography (GC), as before. The analysis was
done using diphenyl oxide as an internal standard.
3. Synthesis of m-Phenoxybenzaldehyde (MPB) by
Rosenmund Reduction. (a) Preparation of Acid Chloride
of m-Phenoxybenzoic Acid. Experimental Procedure and
Setup. The carboxylic acid (107 g), thionyl chloride (90 g),
toluene (600 mL) and N,N-dimethylformamide (2 mL) were
charged in the reactor. The reaction mixture was refluxed at
80 °C in a water bath for 4 h. Gaseous sulfur dioxide,
hydrochloric acid, and unreacted thionyl chloride escaping
from the condenser were trapped in the water and alkali traps.
After the completion of the reaction, the unreacted thionyl
chloride was removed under vacuum. Then 25 mL of toluene
was added, and the mixture of toluene and thionyl chloride
was removed under vacuum. This process was repeated 4-5
times to remove traces of thionyl chloride, whose presence
might affect the activity of the catalyst used in the Rosen-
mund reduction. Finally, m-phenoxybenzoyl chloride was
distilled under vacuum.
(b) Synthesis of m-Phenoxybenzaldehyde (MPB) from Acyl
Chloride. Experimental Procedure and Setup. The acid
chloride in a suitable solvent and the catalyst were taken in
the reactor. Then hydrogen gas was bubbled through the
reaction mixture at a slow constant rate at atmospheric
pressure. It was ensured that there was always a positive
flow of hydrogen at the outlet of the reactor by connecting
to a scrubber containing the solvent. At regular intervals,
samples were withdrawn.
Analysis
Analytical Section
Analysis of Aldehyde Formed in the Reaction by
Oximation. In a typical procedure, an accurately measured
organic layer was diluted with methanol, and the pH of the
Estimation of Aldehyde. The analysis by GC was done
as before by using diphenyl oxide as an internal standard.
Aldehyde was also analyzed by oximation method.
Estimation of Unreacted Acid Chloride. The analysis
of acyl chloride was carried out by Volhard’s method as
given before.
(16) Mosettig, E. Org. React. 1948, 4, 362-77.
(17) Vogel, A. I. QuantitatiVe Inorganic Analysis; Longman Group Ltd.: London,
1975.
418
•
Vol. 3, No. 6, 1999 / Organic Process Research & Development

Table 1. Effect of Type of Catalysta
catalyst
conversion, %
nil
copper
5.5
22
cuprous chloride
29
a Reaction conditions: initial concentration of potassium cresolate, 32% w/v;
bromobenzene, 35 mL; catalyst, 4% w/v; temperature, 180 °C; atmospheric
conditions; time, 6 h.
Table 2. Effect of Halobenzenes and N,N-dimethyl
Formamide As Cosolventa
N,N-dimethyl formamide
conversion (%)
nil (chlorobenzene)
6% (w/v of chlorobenzene)
nil (bromobenzene)
9% (w/v of bromobenzene)
16% (w/v of bromobenzene)
10b
32.5b
31.5
52
78
a Reaction conditions: initial concentration of potassium m-cresolate, 32%
w/v; bromobenzene, 45 mL; cuprous chloride, 1.7 g; temperature 180 °C;
atmospheric conditions; time, 6 h. b Time - 16 h.
Figure 2. Effect of temperature reaction conditions: potassium
m-cresolate, 32% w/v; bromobenzene, 45 mL; cuprous chloride,
1.7 g; DMF, 9% w/v; atmospheric conditions; time, 6 h.;
temperature 180 °C.
Table 3. Effect of Polyethlene Glycol As a Cosolventa
Table 4. Material Balance for m-Phenoxy Toluenea
PEG -4000
conversion, %
input
mol
%
nil
68
79
86
87
m-cresol taken (as K-salt)
0.0963
mol
100
%
5% w/v of chlorobenzene
10% w/v of chlorobenzene
15% w/v of chlorobenzene
output
potassium cresolate
m-phenoxytoluene (isolated)
residue
0.0076
0.0828
0.0027
8.1
83
2.8
a Reaction conditions: initial concentration of potassium cresolate, 32% w/v;
chlorobenzene, 44 mL; cuprous chloride, 2 g; PEG-4000, 1.05 g.; temperature,
250 °C; time, 12 h; pressure, 4 atm.
93.9
a Reaction conditions: initial concentration of potassium m-cresolate, 32%
w/v; chlorobenzene, 45 mL; cuprous chloride, 2 g; PEG- 4000, 1.05 g.;
temperature, 250 °C; time, 12 h; pressure, 4 atm.
Results and Discussion
Definitions. ConVersion. The conversion is defined as the
ratio of total moles of reactant reacted to the moles of the
reactant initially taken.
SelectiVity. The selectivity to a particular product is
defined as the ratio of the moles of the reactant reacted for
the formation of that particular product to the moles of
reactant reacted.
chlorobenzene, which is relatively much cheaper, is therefore
feasible, and the same is recommended. It may be noted that
DMF cannot be used above 180 °C because of its tendency
to decompose, and hence at 250 °C PEG-4000 was used.
Material Balance. It was possible to account for 94%
material balance on the basis of the limiting reactant, Viz.,
potassium cresolate. The product MPT was distilled under
vacuum at 5 Torr. (Table 4).
1. Synthesis of m-Phenoxytoluene (MPT)
Effect of Process Parameters on Reaction Rate and
Selectvity with respect to MPT. The use of cuprous chloride
as a catalyst and the use of cosolvent such as DMF and PEG-
4000 was found to enhance the reaction rate (Tables 1-3).
As expected bromobenzene gave higher conversions com-
pared to chlorobenzene at 180 °C (Table 2). The effect of
temperature was studied in the range of 140 to 180 °C with
DMF as cosolvent using bromobenzene; it was found that
as the temperature was raised from 140 to 180 °C the
conversion increases (Figure 2) but the selectivity decreases
from 99 to 92% due to the formation of residue.
Kinetic Interpretation. Typical kinetic runs with differ-
ent initial concentration of potassium salt of m-cresol are
given in Figure 3. As the substrate concentration was
increased from 32 to 48% the rate of the reaction also
increased. It is expected to be a second order reaction, the
reaction rate being directly proportional to the concentration
of potassium phenoxide and chlorobenzene. Since the
potassium salt of m-cresol has very limited solubility in the
reaction medium, even in the presence of cosolvent, such
as, DMF or PEG-4000, the reaction system is heterogeneous,
and the dissolved concentration of potassium salt of the
phenol in the reaction medium would remain constant for a
given solvent system and temperature. Also, as chloroben-
zene is used in excess compared to cresol salt, the overall
reaction is supposed to follow the first-order kinetics with
However, if higher temperature of 250 °C is used,
conversion to, and selectivity of 86 mol % and 97%,
respectively, could be obtained even in the case of chlo-
robenzene (Table 3). The substitution of bromobenzene by
Vol. 3, No. 6, 1999 / Organic Process Research & Development
•
419

Effect of process parameters on reaction rate and
selectivity. Effect of Different Promoter. Among sodium
bromide and paraldehyde used as promoter, the former was
preferred because although the conversion was less the
selectivity was comparatively high (Table 6). Therefore,
subsequent work was carried out with sodium bromide as
catalyst promoter. Using cobalt acetate and sodium bromide,
when copper acetate was incorporated in the catalyst system,
the combined selectivity towards aldehyde and ester in-
creased markedly although the reaction rate was drastically
low as revealed (Table 6) by the period of reaction which
increased from 0.5 to 5 h for similar conversion.
Effect of Period of Reaction and Substrate Concentration.
The reaction was carried out by varying the amount of
substrate in the range of 25-35% w/v of the total reaction
mixture at 110 °C under a pressure of 12 atm. It was observed
that high selectivity was obtained at higher substrate
concentrations (Figure 4). Therefore for further work 35%
w/v of reactant was used.
Figure 3. Effect of substrate concentration on rate of the
reaction. Reaction conditions: potassium m-cresolate, 32% w/v;
chlorobenzene, 44 mL; PEG-4000, 1.05 g; cuprous chloride, 2
g; temperature, 250 °C; time, 12 h; pressure, 4 atm.
With an increase in period of reaction from 10 to 30 min
the conversion increased from 5.9 to 24%, but the selectivity
of the aldehyde decreased from 46.5 to 37% (Figure 5).
Although a selectivity of 46.5% is comparatively better, the
conversion is too low to be carried out on an industrial scale;
therefore, the conversion level was restricted to 24%.
Effect of Air Pressure and Flow Rate. With the increase
in air pressure from 4 to 14 atm, conversion increased
markedly but the selectivity to the aldehyde decreased
marginally. At 12 atm the conversion and selectivity leveled
off and the same was chosen for further work (Figure 6).
As expected when the flow rate was increased from 20
to 40 mL/s, conversion level increased, and the selectivity
at the same level of conversion was comparable; therefore,
for further work flow rate of 30 mL was used (Figure 7).
Effect of Temperature. The temperature was varied in the
range of 90-120 °C, and the conversion increased marginally
with substantial increase in selectivty (Figure 8). To obtain
a reasonable selectivity at acceptable conversion levels, a
temperature of 110 °C was selected for further work.
Table 5. Effect of Salt on Rate Constanta
time, h
conversion, %
specific reaction rate (k)
3
6
8
12
16
46.3
65.3
73
84
89.3
5.76 × 10-5
4.9 × 10-5
4.55 × 10-5
4.24 × 10-5
3.88 × 10-5
a Reaction conditions: initial concentration of potassium m-cresolate, 32%
w/v; chlorobenzene, 44 mL; cuprous chloride, 2 g; PEG 4000, 1.05 g.;
temperature, 250 °C; pressure, 4 atm.
respect to m-cresolate for which the specific reaction rate
was determined. As mentioned in a reference,18 the conver-
sion level decreases markedly towards the completion due
to potassium chloride formed during the reaction. This “salt
effect” is particularly pronounced because the amount of
potassium salt of m-cresol used is at a higher concentration
in the range 32-48% w/v on the basis of solvent, as the
resulting amount of potassium chloride will also be quite
high which influences the kinetics (Table 5).
Synthesis of m-Phenoxybenzaldehyde by Rosenmund
Reduction
Effect of Process Parameter on Reaction Rate and
Selectivity. Effect of Acylating Reagent. Acylation of MPBA
was carried out with thionyl chloride and phosphoryl chloride
to give m-phenoxybenzoyl chloride. SOCl2 was found to give
comparatively higher yields (Table 7). Therefore, further
work was carried out using thionyl chloride as the acylating
agent.
Effect of Speed of Agitation. Speed of agitation was varied
from 500 to 1200 rpm (Figure 9). There was no significant
change in the conversion obtained beyond 1000 rpm, thereby
indicating that the effects of mass transfer from the gas phase
to gas-liquid interface is completely eliminated. Further
observation, that the initial reaction rate was proportional to
catalyst loading (Figure 10), corroborated the finding that
the process was kinetically controlled.
2. Synthesis of m-Phenoxybenzaldehyde (MPB) by Air
Oxidation of m-Phenoxytoluene (MPT)
The reactions, as mentioned in the literature, are carried
out using acetic acid as a solvent, and the catalyst used was
cobalt(II) acetate as claimed by most of the patentees.
The formation of the aldehyde is accompanied with the
formation of m-phenoxybenzyl acetate by the condensation
of alcohol; an intermediate in the process, presumably with
acetic acid. The acetate formed can be converted back to
aldehyde by hydrolysis to the alcohol followed by oxidation
with sodium hypochlorite.19 Since the acetate is also used
as an intermediate for pyrethroid, total selectivity of acetate
and aldehyde was also considered.
Effect of Type of SolVent. The reduction was carried out
using different solvents such as toluene, acetone, and ethyl
(18) Moroz, A. A.; Shvartsberg, M. S. Russ. Chem. ReV. 1974, 43 (8), 679-
(19) 6A8l6o.k, A. S.; M. Chem. Eng. Thesis, University of Bombay, 1994.
420
•
Vol. 3, No. 6, 1999 / Organic Process Research & Development

Table 6. Effect of Different Promotera
conversion
acid selectivity
(%)
ester selectivity
(%)
aldehyde selectivity
(%)
total selectivity
(%)
catalyst system
(%)
cobalt acetate + paraldehyde
cobalt acetate + sodium bromide
cobalt acetate + copper acetate +
sodium bromide
33
24
18
57
31
25
17
30.6
35
24
37
40
41
67.6
75
a Reaction conditions: initial concentration of m-phenoxytoluene, 35% w/v, cobalt acetate, 5 g; sodium bromide, 3.2 g; copper acetate, 3.2 g; temperature, 110 °C,
solvent, acetic acid; total volume 300 mL; time, 0.5 h; flow rate, 30 mL/sec; air pressure, 12 atm.
Figure 6. Effect of air pressure on rate of the reaction. Reac-
tion conditions: m-Phenoxytoluene, 35% w/v; cobalt acetate,
5 g; sodium bromide, 3.2 g, temperature, 110 °C, time, 0.5 h;
solvent, acetic acid, total volume, 300 mL; flow rate, 30 mL/s.
Figure 4. Effect of substrate concentration. reaction condi-
tions: cobalt acetate, 5 g; sodium bromide, 3.2 g, temperature,
110 °C, time, 0.5 h; solvent, acetic acid, total volume, 300 mL;
flow rate, 30 mL/s; air pressure, 12 atm.
Figure 7. Effect of air flow rate on rate of the reaction.
Reaction conditions: m-phenoxytoluene, 35% w/v; cobalt
acetate, 5 g; sodium bromide, 3.2 g; temperature, 110 °C; time,
0.5 h; solvent, acetic acid, total volume, 300 mL; air pressure,
12 atm.
Figure 5. Effect of period of reaction. reaction conditions:
m-phenoxytoluene, 35% w/v, cobalt acetate, 5 g; sodium
bromide, 3.2 g, temperature, 110 °C, solvent, acetic acid, total
volume, 300 mL; flow rate, 30 mL/s; air pressure, 12 atm.
As the amount of acyl chloride was varied in the range of
10-20% w/v (Figure 11), the selectivity to the aldehyde
increased marginally, but the overall conversion was found
to decrease (Table 9).
acetate (Table 8). It was observed that the conversion levels
and selectivity remained almost similar with a marginal
change. Further work was done by using toluene as the
solvent.
At a substrate concentration of 10% w/v, with the increase
in the reaction period from 0.25 to 3 h, the conversion of
Effect of Initial Concentration of m-Phenoxybenzoyl
Chloride and Period of Reaction on the Rate of Reduction.
Vol. 3, No. 6, 1999 / Organic Process Research & Development
•
421

Figure 8. Effect of temperature on the rate of reaction reaction
conditions: m-phenoxytoluene, 35% w/v; cobalt acetate, 5 g;
sodium bromide, 3.2 g, time, 0.5 h; solvent, acetic acid, total
volume, 300 mL; air pressure, 12 atm; flow rate, 30 mL/s.
Figure 10. Effect of catalyst loading. Reaction conditions:
initial concentration, 10% w/v; speed of agitation, 1000 rpm;
temperature, 30 °C; solvent, toluene; reaction volume, 100 mL.
Table 8. Effect of Type of Solventa
Table 7. Effect of Acylating Reagenta
type of solvent
conversion, %
selectivity, %
acylating reagent
conversion, %
selectivity, %
toluene
acetone
ethyl acetate
67.5
66
65.5
92
91
90.5
SOCl2
POCl3
67
65
92
89
a Reaction conditions: initial concentration of m-phenoxybenzoyl chloride,
10% w/v; speed of agitation, 1000 rpm; catalyst loading, 1.5% w/v; time, 1 h;
time, 2 h; solvent, toluene, 100 mL.
a Reaction conditions: initial concentration of m-phenoxybenzoyl chloride,
10% w/v; speed of agitation, 1000 rpm; catalyst loading, 1.5% w/v; temperature,
30 °C; time, 2 h; solvent, toluene, 100 mL.
Figure 11. Effect of substrate concentration on conversion.
Reaction conditions: catalyst loading, 1.5% w/v; speed of
agitation, 1000 rpm; temperature, 30 °C; solvent, toluene, 100
mL.
Figure 9. Effect of speed of agitation. Reaction conditions:
initial concentration, 10% w/v; catalyst loading, 1.5% w/v;
temperature, 30 °C; solvent, toluene; reaction volume, 100 mL.
m-phenoxybenzoyl chloride increased from 14 to 81%, while
the selectivity decreased from 96 to 88% (Figure 12).
Effect of Temperature. The reaction temperature was
varied from 20 to 40 °C which increases the conversion from
35 to 84% in 2 h (Figure 13). It was observed that the
selectivity towards aldehyde decreases from 98 to 84% due
to the formation of alcohol (Table 10).
Effect of Catalyst Loading. The catalyst loading expressed
as the wt % of catalyst based on the total reaction volume
was varied at 1, 1.3, and 1.5% w/v of reaction mixture, using
422
•
Vol. 3, No. 6, 1999 / Organic Process Research & Development

Table 9. Effect of Substrate Concentration on Selectivitya
Table 10. Effect of Temperaturea
substrate concentration %, w/v conversion, % selectivity, %
temperature, °C
conversion, %
selectivity, %
10
15
20
40
34
28
94
95
98
20
30
40
35
67
84
98
92
84
a Reaction conditions: speed of agitation, 1000 rpm; catalyst loading, 1.5%
w/v; temperature, 30 °C; time, 1 h; solvent, toluene, 100 mL.
a Reaction conditions: initial concentration of m-phenoxybenzoyl chloride,
10% w/v; speed of agitation, 1000 rpm; catalyst loading, 1.5% w/v; time, 2 h;
solvent, toluene, 100 mL.
Figure 12. Effect of period of reaction on conversion. Reaction
conditions: initial concentration, 10% w/v; speed of agitation,
1000 rpm; catalyst loading, 1.5% w/v; temperature, 30 °C;
solvent, toluene; reaction volume, 100 mL.
Figure 14. Effect of catalyst loading. Reaction conditions:
initial concentration, 10% w/v; speed of agitation, 1000 rpm;
temperature, 30 °C; solvent, toluene, 100 mL.
Table 11. Effect of Reusability of Catalysta
catalyst
conversion, %
fresh
85
83.5
82
1st use
2nd use
3rd use
80
a Reaction conditions: initial concentration of m-phenoxybenzoyl chloride,
10% w/v; speed of agitation, 1000 rpm; catalyst loading, 1.5% w/v; temperature,
30 °C; time, 4 h; solvent, toluene, 100 mL.
Conclusions
Synthesis of m-Phenoxytoluene. 1. Under suitable reac-
tion conditions using PEG-4000 as the cosolvent the Ullmann
condensation of potassium salt of m-cresol with chloroben-
zene gave 86% conversion to m-phenoxytoluene with 97%
selectivity in 12 h.
2. The rate of reaction decreases towards the end of the
reaction due to the salt effect of potassium chloride.
3. The formation of residue was less than 3% when the
reaction was carried out for 12 h at 250 °C.
Synthesis of m-Phenoxybenzaldehyde by Air Oxida-
tion. 1. Air oxidation of m-phenoxytoluene to m-phenoxy-
benzaldehyde in the presence of cobalt acetate and sodium
bromide gave a selectivity of 37 and 30.6% towards aldehyde
and the ester, respectively, at a conversion of 24%.
Figure 13. Effect of temperature. Reaction conditions: initial
concentration, 10% w/v; speed of agitation, 1000 rpm; catalyst
loading, 1.5% w/v; solvent, toluene, 100 mL.
Pd/C as catalyst (Figure 14). As expected higher conversions
were obtained with higher catalyst loading.
Effect of Catalyst Reusability. The catalyst could be reused
for 3 times with marginal decrease in the conversion levels
(Table 11).
Vol. 3, No. 6, 1999 / Organic Process Research & Development
•
423

2. The use of 1.5% w/v of copper acetate in addition to
sodium bromide and cobalt acetate as catalyst gave a
comparatively higher selectivity of 40 and 35% compared
to 37 and 30.6% with respect to the aldehyde and the ester,
respectively, but the reaction rate drastically decreased,
comparable conversion being obtained in 5 h instead of 0.5
h.
Synthesis of m-Phenoxybenzaldehyde by Rosenmund
Reduction. 1. The hydrogenation of m-phenoxybenzoyl
chloride to m-phenoxybenzaldehyde gave 93% conversion
to the product with a selectivity of 86% at 10% substrate
concentration, 30 °C and a catalyst loading of 1.5% w/v.
2. With the increase in substrate concentration, the
conversion to the aldehyde decreased.
3. The catalyst Pd/C could be reused three times with
marginal decrease in the conversion level.
Acknowledgment
K.H.C. is grateful to Professor S. B. Chandalia for
arranging stipends by means of projects through out the work.
Received for review April 7, 1999.
OP990028Z
424
•
Vol. 3, No. 6, 1999 / Organic Process Research & Development