Note: Descriptions are shown in the official language in which they were submitted.
212b~ ~ 6
Merck Patent Gesellschaft
mit beschrankter Haftung
6100 D a r m s t a d t
Process for the preparation of indoles
The invention relates to a new process for the
preparation of indoles by decarboxylation of correspond-
ing indole-2-carboxylic acids.
Indole-2-carboxylic acids have been conventional-
ly decarboxylated by heating them, dissolved in a high-
boiling tertiary amine, at reflux (cf. e.g. ~ouben-Weyl/
M~ller, Methoden der organischen Chemie [Methods of
Organic Chemistry]; 1952, volume 8, page 486).
For instance, 4-(5-methoxy-3-indolyl)butyric
acid (I), an intermediate for the synthesis of roxindol,
has previously been prepared by heating a solution of 3-
(3-carboxypropyl)-5-methoxyindole-2-carboxylic acid (II)
in N,N-dimethylaniline or N,N-tiethylaniline at 190~ for
24 hours.
Disadvantages here are the high reaction tempera-
ture and the apparatus-related problems which it entails,
permitting production in only a few plants, and also the
long reaction time and the consequently high consumption
of energy.
The object of the invention was to find a new
process for the preparation of indoles, especially I, in
which the abovementioned disadvantages are greatly
reduced or totally absent.
It has been found that I is obtained in a high
yield if a solution of II in formic acid is heated. This
is surprising inasmuch as indoles are generally con-
sidered to be highly labile with respect to acids. This
has also been demonstrated in attempts to replace formic
acid by other acids, such as acetic acid, dilute aqueous
sulfuric acid or dilute aqueous hydrochloric acid. Either
there was no reaction at all or I was obtained in only a
low yield with the formation of by-products.
The process can be transferred with a high degree
of success to other indole-2-carboxylic acids.
2126~1~
-- 2 --
The invention relates to a process for the
preparation of indoles by decarboxylation of correspond-
ing indole-2-carboxylic acids, characterized in that
these acids are treated with formic acid.
In this process, the formic acid used may ex-
pediently contain about 0-50 % water. The reaction
temperatures are between 20 and 107 and preferably
between ao and 107 C. The reaction times required at the
higher temperatures are between about 1 and 10 hours,
preferably between 2 and 4 hours, while those required at
the lower temperatures are corresponding longer.
The percentages given below are percentages by
volume.
Example 1
A mixture of 14.2 g of II and 120 g of 77.4 %
formic acid is boiled for 3 houxs and then evaporated
under reduced pressure. Dilute sodium hydroxide solution
is added to the residue, clarification is carried out
briefly with activated carbon at 40, and the product is
precipitated with hydrochloric acid to pH 1.5. The
precipitated I is filtered off, washed with water and
dried under reduced pressure at 50. Yield: 10.9 g.
Example 2
The procedure is as indicated in Example 1 but
using 100 % formic acid with a reaction time of 2 hours.
Example 3
The procedure is as indicated in Example 1 but
using 50 % formic acid; reaction time: 5 hours.
Example 4
The procedure is as indicated in Example 1, but
at 80; reaction time: 30 hours.
Example 5
Indole is obtained from indole-2-carboxylic acid,
analogously to Example l.
