Table 1. Oxidative chlorination of MBSA: effect of mode of
baffles, a dropping funnel, and a water condenser. The
outgoing gases were passed through a caustic scrubber. The
assembly was kept in a constant-temperature bath. A
predetermined quantity of substrate and 35% hydrochloric
acid were dissolved in the solvent, and the reaction mixture
was kept at the desired temperature. A measured quantity
of 30% hydrogen peroxide was added dropwise to the
reaction mixture over a predetermined period of time, while
maintaining the desired temperature within the specified
range. For MBSA, the reaction mixture was directly taken
for the desulphonation step without isolation. In the case of
benzoic acids, after the stipulated reaction period, the reaction
mixture was chilled and then filtered to remove the precipi-
tated products. The products were then dried and taken for
the decarboxylation step. In the case of 4-methylphenol, the
reaction mixture was distilled to isolate the desired 2-chloro-
4-methylphenol.
reactiona
mode of addition
% overall conversion
% selectivity
batch mode
semibatch mode
47
86
83
98
a Reaction conditions: reactant concentration, 0.87 gmol/L; hydrochloric acid,
3.48 gmol/L; hydrogen peroxide: 0.783 gmol/L; temperature, 45 °C; time, 4 h.
Table 2. Oxidative chlorination of MBSA: effect of addition
timea
% selectivity to
chloro compound
addition time (h)
% overall conversion
1.0
1.5
2.0
3.0
59
67
70
86
89
92
94
98
For desulphonation, a measured quantity of the reaction
mixture after oxidative chlorination was taken into the
reactor, and a calculated amount of 98% sulphuric acid was
added to the reaction mixture to obtain the desired concen-
tration of sulphuric acid in the bulk. The reaction mixture
was then heated to attain the desired temperature and was
kept over a specified period of time. After the stipulated
reaction period, the reaction mixture was extracted with
toluene. The organic layer was washed with 5% NaOH
solution to remove the unreacted sulphonic acid. Then the
organic layer was dried on sodium sulphate and distilled
under vacuum to isolate the desired product.
A 100-mL autoclave was used for the decarboxylation
reactions. Predetermined quantities of chlorosubstituted ben-
zoic acid, solvent, and catalyst were charged in the autoclave.
The autoclave was heated to the desired temperature and kept
for a specified period of time. After the stipulated period of
time, the reaction mixture was distilled under vacuum, using
a 1-m wire mesh-packed column to isolate the desired
2-chloro compound.
a Reaction conditions: reactant concentration, 0.87 gmol/L; hydrochloric acid,
3.48 gmol/L; hydrogen peroxide, 0.783 gmol/L; temperature, 45 °C.
SelectiVity. The selectivity to a particular product is
defined as the ratio of the number of moles of the reactant
reacted for the formation of that particular product to the
number of moles of reactant reacted.
Process Parameter Studies. The effects of different
important process parameters on the rate of oxidative
chlorination of MBSA were studied to determine the most
suitable reaction conditions for maximum conversion and
selectivity to monochloro products.
Mode of Reaction and Addition Time of Hydrogen
Peroxide on the Rate of Oxidative Chlorination of MBSA.
To determine the mode of reaction to achieve maximum
conversion and selectivity, the reaction was studied in batch
mode as well as semibatch mode (Table 1). It was observed
that when hydrogen peroxide was added dropwise, both the
conversion and the selectivity with respect to the desired
product increased due to the maximum utilization and control
of hydrogen peroxide concentration in the reaction mixture.
A 3-h addition time was preferred under these reaction
conditions to achieve maximum selectivity and utilization
of hydrogen peroxide (Table 2).
Analytical Procedure. The reaction mixture after oxida-
tive chlorination was analyzed by HPLC, under the following
conditions: column, MERCK 50983, Lichrosphere 100 RP-
18, 5 µm, 254 × 4 mm; mobile phase, water-acetonitrile,
3:2; flow rate, 1 mL/min; wavelength, 254 nm.
Effect of Solvent on the Rate of Oxidative Chlorina-
tion. Different solvents such as acetic acid, aqueous hydro-
chloric acid, and dichloro ethane were used for these
reactions. Due to the difference in the solubility of the starting
materials in different solvent systems, the rate of reaction
was different in each case.
In acetic acid, the rate of oxidative chlorination varied in
the order 4-methylphenol > 4-hydroxybenzoic acid >
4-aminobenzoic acid > 4-methylbenzoic acid under the same
reaction conditions (Table 3).
In aqueous HCl, the rate of oxidative chlorination under
identical conditions followed the order 4-methylbenzenesul-
phonic acid > 4-aminobenzoic acid > 4-methylphenol >
4-hydroxybenzoic acid > 4-methylbenzoic acid (Table 4).
And in dichloroethane, the rate followed the order
4-methylphenol > 4-hydroxybenzoic acid > 4-aminobenzoic
acid > 4-methylbenzoic acid (Table 5).
The conditions for GC used to analyze the reaction
mixtures after desulphonation reaction were as follow:
column, OV-17, 4 m; oven temperature, 60 °C, 5 °C/min,
120 °C, 10 °C/min, 300 °C, 5 min; injector temperature, 300
°C; detector temperature, 300 °C.
Unreacted chlorosulphonic acid was analyzed by HPLC,
under the same conditions as those given for oxidative
chlorination.
After decarboxylation, the reaction mixtures were ana-
lyzed by GC as well as HPLC under the same conditions as
given above.
Results and Discussion
Definitions. ConVersion. The conversion is defined as the
ratio of the number of moles of the reactant reacted to the
number of moles of the reactant taken.
Vol. 3, No. 3, 1999 / Organic Process Research & Development
•
197