PROCESS FOR THE PREPARATION OF 2,3-DICHLOROANISOLE

OBTENTION DE 2,3-DICHLOROANISOLE

English Abstract

ABSTRACT OF THE DISCLOSURE
Sodium methylate is reacted in an aprotic polar
solvent or in a mixture of such solvents with 1,2,3-trichloro-
benzene in the presence of a cuprous catalyst and at temperatures
ranging between 70°C and the boiling temperature of the solvent
to produce 2,3-dichloroanisole which is useful in particular
for the preparation of 2,3-dichloro-4-(2-thenoyl) phenoxyacetic
acid - valuable diuretic and uricosuric agent.

Claims

The Embodiments of the Invention in Which an Exclusive
Property or Privilege is Claimed are Defined as Follows:
1. A process for the preparation of 2,3-dichloro-
anisole, which comprises reacting sodium methylate in an aprotic
polar solvent or in a mixture of such solvents with 1,2,3-tri-
chlorobenzene, in the presence of cuprous bromide, iodide or oxide
and at temperatures ranging between 70°C and the boiling tempera-
ture of the solvent.
2. Process according to Claim 1, wherein the solvent
is selected from the group consisting of dimethylformamide, the
dimethyl ether of ethyleneglycol, the dimethyl ether of diethyl-
eneglycol, and mixtures thereof to form an aprotic polar solvent.
3. Process according to Claim 2, wherein a mixture
of dimethyl ether of ethyleneglycol and of dimethylformamide is
used as a solvent.

Description

1091'~55
The present invention is concerned with a new process
for the preparation of 2,3-dichloro anisole.
2,3-dichloro anisole is a compound known for a number
of years and used especially in the preparation of 2,3-dichloro-
4-(2-thenoyl) phenoxyacetic acid - diuretic and uricosuric agent.
It has been prepared, in particular, by the reaction of a methyl-
ation agent with 2,3-dichlorophenol (Holleman, Recueil des
Travaux Chimiques des Pays-Bas 37,104) or by the reaction of
sodium methylate with 1,2,3-trichlorobenzene in solution in meth-
anol at 180C ~Holleman, Recueil des Travaux Chimiques des Pays-
Bas 37,200). In the latter case, numerous products are formed
and the overall yield of the reaction is limited.
This invention is concerned with a new process for
the preparation of 2,3-dichloro anisole from 1,2,3-trichloro-
benzene a rather inexpensive commercial product. The process
makes it possible to obtain anisole with high yields and without
the formation of by-products. This process is much easier to
apply than the previously described process which also uses
sodium methylate as it is carried out at ordinary pressure and
at only slightly elevated temperatures. The use of such a
process makes it possible to obtain dichloroanisole and conse-
quently 2,3-dichloro-4-(2-thenoyl) phenoxyacetic acid, more
economically.
The process according to the invention consists of
reacting sodium methylate with 1,2,3-trichlorobenzene in solu-
tion in a polar aprotic solvent, or in a mixture of such solvents,
as for example dimethylformamide, the dimethyl ether of ethylene-
glycol, the dimethyl ether of diethyleneglycol, in the presence
of catalytic quantities of copper in the form of iodide, bromide,
or cuprous oxide, at temperatures ranging between 70C and the
boiling temperature of the solvent used. ~nder these conditions,
no rearrangement is observed of the benzene ~ing substituents -
- 1- ~

lV~ S
known rearrangements - which in general indicates the formation
of a benzyne, nor is any substitution of two or three of the
halogen atoms of the benzene ring o~served, even in the presence
of an excess of sodium methylate.
The following examples illustrate the in~ention with-
out consequently limiting it.
EXAMPLE 1
12.2 g of sodium is dissolved in 250 ml of anhydrous
methanol and the solvent eliminated to isolate the product MeONa
from MeOH. The product is placed in suspension in 60 ml of
dimethyl ether and ethyleneglycol and the suspension is poured
into 200 ml of anhydrous dimethylformamide. 80 g of trichloro-
benzene and 2 g of cuprous iodide is added to the medium and
maintained at about 75C for a least 8 hours. During this
period, it is possible to add additional sodium methylate to
the medium in order that the reaction may take place more quickly.
After cooling, the solution is filtered and poured into 4 volumes
of water saturated with sodium chloride; dichloroanisole and
dichlorobenzene is then extracted from this mixture, in dichlor-
ethane. After desiccation of the solution and evaporation ofthe solvents, 16 g of dichloroanisole is obtained in the form
of an oil, which contains a small amount of trichlorobenzene.
To isolate the final product, rather than pouring the
reacting medium into the water after filtration, it is possible
to eliminate the solven~s under reduced pressure. In order to
; separate the dichloro anisole from the remaining traces of
trichlorobenzene, the crude oil obtained is distilled under
ordinary pressure (E = 230~C) or under reduced pressure
(E15 = 114C) or the mixture is steam-distilled, trichlorobenzene
being distilled first. In this way pure crystallized 2,3-
dichloroanisole is obtained (F = 33C~ with a yield of more
than 85%.

1091;~.~5
In this reaction, it is also possible to use sodium
methylate from which any solvent has been remoYed by heating to
a temperature greater than 200C. There is also the possibility
of adding less than the stoichiometric quantity of methylate
to the medium at the beginning of the reaction, but effecting
several additions during heating.
EXAMPLE 2
; 0.1 mole of sodium methylate is prepared by dissolving
2.3 g of sodium in 50 ml of methanol. 100 ml of anhydrous
dimethylformamide is then poured into the solution and the
methanol is rapidly evaporated under reduced pressure. Then
5.45 g of trichlorobenzene and 1 g of CuI is added to the medium,
: which is brought to 120C in 2 hours. The medium is then cooled,
filtered, and poured into 3 volumes of water. The solution is
saturated, e.g., by adding sodium chloride, after which it is
placed in contact with a solvent not miscible with water, such
-; as ethyl ether or dichlorethane. The organic phase is decanted
and dried, after which the solvent is evaporated. 5 g of oily
residue is obtained, which contains a mixture of dichloro-
2Q anisole ~80~ and of starting product. This mixture is purified
as described in Example 1.
.
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