The Manufacture or Production of Pharmaceutical Compounds.
Year: 1894

page_text: Date of Application, 22nd Nov., 1894
Complete Specification Left, 16th Aug., 1895-Accepted, 21st Sept., 1895
[Communicated from abroad by THE FARBENFABRIKEN, vormals FRIEDRICH
BAYER & Co., of Elberfeld, Germany.]
The Manufacture or Production of Pharmaceutical Compounds.
I, HENRY EDWARD NEWTON of The Office for Patents, 6 Bream's Buildings,
Chancery Lane in the County of London, Patent Agent, do hereby declare the
nature of this invention to be as follows:-
My foreign correspondents have described in the Specification of Letters Patent
No. 11833, dated 11th July 1891, a process for producing acetylamidosalol, or
acetylamidophenylic salicylate, and homologues thereof. Unlike the salol, which
is, chemically, phenylic ester of salicylic acid, or phenylic salicylate, the said
products are destitute of any toxic properties, and they can therefore be used
profitably for therapeutic purposes in place of salol, as mentioned in the aforesaid
Specification. Another method of preparing the acetyl compounds herein before
referred to, is described in the Specification of Letters Patent No. 3435, dated
22nd February 1892.
My foreign correspondents have now discovered, that other acid derivatives of
amidosalol, or the like, exhibit the same favourable effects as the said acetyl
products, and that the lactyl derivatives have a special value, inasmuch as they
are superior to the acetyl compounds, by reason of their greater solubility in
water.
According to the researches of ny foreign correspondents, the lactyl derivatives
of amido salol, or the like, can be produced, in general, by means of the methods
described in the Specifications of the before mentioned two Letters Patent for
preparing the corresponding acetyl compounds, that is to say by suitably intro-
ducing the lactyl radicle in place of the acetyl radicle, which process can be
effected, for instance, by treating amidosalol, or the like, with lactic acid, lactic
anhydride, lactide or lactic ester, or by heating a salt of amidosalol together with
lactic amide.
In order to illustrate the production of the lactyl compounds hereinbefore
defined, the following examples are given. The parts are by weight.
PRODUCTION OF LACTYLAMIDOSALOL FROM PARAMIDOPHENYL
SALICYLIC ACID AND LACTIC ANHYDRIDE.
ESTER OF
A mixture prepared from 1 part of paramidophenyl ester of salicylic acid
(amidosalol) and part of lactic anhydride, is heated at about 150 degrees Centi-
grade for hour. After cooling, water is added, and the undissolved residue is
filtered off and crystallised from dilute alcohol.
COND

page_text: amide, is heated at from 160 to 170 degrees Centigrade. Ammonium chloride
soon begins to separate from the molten mass. After heating for, say, hour,
the mass is treated with water. The residue, insoluble in water, is filtered off,
and crystallised from dilute alcohol.
The lactyl amidosalol, or lactyl amidophenylic salicylate, obtained according to
the processes described in the above examples, crystallises from alcohol in white
scales, which melt at 268 degrees Centigrade. This substance dissolves with
difficulty in cold water, but with less difficulty in hot water. When boiled with
alkali lye, it is decomposed, lactic anhydride being separated and amidosalol being
recovered.
The corresponding lactyl derivatives of amidophenyl esters of other hydroxy-
carboxylic acids, result in a manner analogous to that described in the examples
given, if either equivalent quantities of the amidophenylesters of ortho- or meta-
or para-cresolcarboxylic acid, or the like, are used in place of amidosalol (amido-
phenylester of salicylic acid) used in the foregoing first example, or if corre-
sponding quantities of salts of amidophenylesters of other hydroxycarboxylic
acids, are employed in place of amidosalolhydrochloride used in the above second
example. The lactylamido compounds thus obtained, in general are similar to the
lactylamidosalol herein before defined.
In the production of the lactylamido compounds, my foreign correspondents do
not limit themselves to the methods illustrated by the said two examples, as the
process can be varied. For instance, lactic anhydride used in the first example, can
be replaced by lactic acid, or other derivatives thereof (such as lactidester, lactide,
or the like). Other salts of amido salol can be used in place of the hydrochloride
used in the second example. The method described in the Specification of Letters
Patent No. 3435 of 1892 can be likewise used. Such or similar modifications do
not alter the nature of this invention, which generally relates to the production of
valuable pharmaceutical compounds which are lactyl derivatives of amidophenyl-
esters of aromatic hydroxycarboxy acids.
Dated this 22nd day of November 1894.
NEWTON & SON,
Agents for the Applicant.
COMPLETE SPECIFICATION.
The Manufacture or Production of Pharmaceutical Compounds.
I HENRY EDWARD NEWTON of The Office for Patents, 6 Bream's Buildings,
Chancery Lane in the County of London, Patent Agent, do hereby declare the
nature of this invention and in what manner the same is to be performed, to be
particularly described and ascertained in and by the following statement :-
My foreign correspondents have described, in the 'Specification of Letters
Patent No. 11833, dated 11th July 1891, a process for producing acetylamidosalol,
or acetylamido phenylic salicylate, and homologues thereof. Unlike salol, which
is chemically defined as phenylic salicylate, the said products are destitute of
toxic properties, and they can therefore be profitably used for therapeutic purposes,
in place of salol, as mentioned in the aforesaid Specification.
My foreign correspondents have now discovered that other acid compounds
derived from amido salol, or the like, exert favorable effects similar to those
produced by the said acetyl products, and that the lactyl derivatives have a special
value, inasmuch as they are superior to the acetyl compounds, owing to their
greater solubility in water.
According to the researches of my foreign correspondents, the lactyl derivatives
of amidosalol, or the like, speaking generally, can be produced by the methods
described in the Specification of the before-mentioned Letters Patent for preparing

page_text: the corresponding acetyl compounds, that is to say, by suitably introducing the
lactyl radicle in place of the acetyl radicle, which process can be effected, for
instance, by acting on amidosalol, or the like, with lactic acid, lactic anhydride,
lactide, or a lactic ethereal salt, or by heating a salt of amidosalol together with
lactic amide.
In order to illustrate the production of the lactyl compounds hereinbefore defined,
the following examples are given. The parts are by weight.
MANUFACTURE OF LACTYLAMIDOSALOL FROM AMIDOSALOLHYDROCHLORIDE
AND LACTIC AMIDE.
A mixture of 1 part of amidosalolhydrochloride and three fourth parts of lactic
amide, is heated at from 160 to 170 degrees Centigrade. Ammonium chloride
After heating during about an
soon begins to separate from the molten mass.
hour, the mass is digested with water, and the insoluble residue is then filtered off
and crystallised from dilute alcohol.
The lactylamidosalol, or lactylamidophenylic salicylate, obtained by carrying
out the processes described in the above examples, crystallises from alcohol in white
scales which melt at 268 degrees Centigrade. The substance dissolves with
When boiled with
difficulty in cold water, but with less difficulty in hot water.
alkali lye, it is resolved into lactic acid and amidosalol.
The corresponding lactyl derivatives of amidophenylic salts of other hydroxy
carboxylic acids are formed in a manner analogous to that described in the
examples given, if either equivalent quantities of the amidophenylic salts of ortho or
meta or paracresolcarboxylic acid, or the like, are used in place of the amidosalol
(amidophenylic salicylate) used in the foregoing first example, or if corresponding
quantities of salts of amidophenylic salts of such hydroxycarboxylic acids are
used in place of the amidosalol hydrochloride of the above second example. The
lactylamido compounds thus obtained are in general, similar to the lactylamido-
salol hereinbefore defined.
In producing the lactylamido compounds hereinbefore defined, my foreign
correspondents do not limit themselves to the methods illustrated by the said two
examples, as the process can be varied. For instance, instead of the lactic
anhydride of the first example, lactic acid, or other derivatives thereof (such as
lactic ethereal salts, lactide, or the like) can be used, and other salts of amidosalol
can be taken in place of the hydrochloride of the second example. Such or
similar modifications do not alter the nature of this invention, which, speaking
generally, relates to the production of valuable pharmaceutical compounds which
are lactyl derivatives of amido phenylic ethereal salts of aromatic hydroxy-
carboxylic acids.
Having now particularly described and ascertained the nature of the said inven-
tion and in what manner the same is to be performed (as communicated to me
from abroad), 1 declare that what I claim is :-
1. The process for producing the lactylamidophenylic salts of salicylic acid,

page_text: ortho cresolcarboxylic acid, metacresolcarboxylic acid, and paracresolcarboxylic
acid, which process consists,
(a) In acting with lactic acid, lactic anhydride, lactide, or a lactic ethereal
salt, on amidosalol, or the homologous amidophenylic salts of orthocresol
carboxylic acid, metacresolcarboxylic acid, or paracresolcarboxylic acid; or
(6) In allowing lactic amide to act on a salt of amidosalol, or of the
homologous amidophenylic salts of orthocresolcarboxylic acid, metacresol-
carboxylic acid, or paracresolcarboxylic acid.
2. As new articles of manufacture, the lactyl amidophenylic salts of salicylic
acid, orthocresolcarboxylic acid, metacresol carboxylic acid, and paracresol-
carboxylic acid, produced by the processes herein before defined, or by any other
means affording the same result.
Dated this Oth day of tract 1905
NEWTON & SON,
Agents for the Applicant.