Process for Obtaining the Lactyl Derivatives of Methyl-aniline, Ethyl-aniline, Para-anisidine, and Para-phenetidine.
Year: 1895

page_text: PROVISIONAL SPECIFICATION.
A Process for Obtaining the Lactyl Derivatives of Methyl-aniline,
Ethyl-aniline, Para-anisidine, and Para-phenetidine.
1, JAMES YATE JOHNSON of 47 Lincoln's Inn Fields in the County of London
Gentleman, do hereby declare the nature of this invention (which has been
communicated to me from abroad by the Chemische Fabrik vorm. Goldenberg
Geromont & Co. of Winkel, Rheingau in the German Empire) to be as follows:-
It is a well known fact that by starting operations with propionic acid, alpha-
hydro oxy-propionic acid, i.e. lactic acid, may be obtained, if the propionic acid be
first converted into propionic acid into which a halogen has been introduced and
replacing the halogen in such an acid by hydroxyl by boiling with water or with
solutions of alkaline hydrates or alkaline carbonates.
Now with the assistance of this lactic acid synthetically obtained from propionic
acid, the process described in the Specification of Letters Patent No. 12166 of
30th June 1892 enables lactyl derivatives to be produced which possess exactly the
same properties as those which are obtained by the employment of lactic acid
resulting from fermentation and described in the Specification to the said Patent
No. 12166".
My foreign correspondents have since ascertained that the lactyl derivatives of
the aromatic bases mentioned in that Patent may be obtained from propionic acid
direct without the necessity of first converting the propionic acid into lactic acid.
It is well known that the halogen-propionyl derivatives of the primary and
secondary bases named may be obtained by means of the chlorides or bromides of
the alpha-halogenysed propionic acids. The halogen-propionyl derivatives are
I emarkably stable against the action of boiling water. By means of solutions of
alkaline hydrates these derivatives are hydrolysed, so that by means of these agents
hydroxyl cannot be substituted for halogen.
By the employment of solutions of carbonates of alkalies halogen metal may,
indeed, be formed yet by this reaction pure products can be obtained only with
difficulty. The alpha halogenized propionyl derivatives of aromatic bases may be
readily converted into lactyl derivatives by boiling the former with salts of
carboxylic acids in aqueous or alcoholic solution. The preferable agents for this
purpose are the acetates of alkalies or alkaline earths. With a view to accelerating
the reaction and render it complete, it is advisable to employ a quantity of acetato
in excess. By raising the temperature, the completion of the reaction may also be
hortened
20 kilogrammes of alpha-brom-propionyl-para phenetidide (the melting point of
which is 135° Centigrade) is dissolved with from 12 to 20 kilogrammes (theoretically
10 kilogrammes) of crystallised acetate of sodium in spirits of wine at 90% and the
solution obtained is boiled in a reflux apparatus until a sample of the liquid
precipitated with water and washed, yields a product free from biomine. Then
the main portion of the alcohol employed is distilled off, the residue discharged
ID 01

page_text: into water and the precipitate washed with water until it is free from bromine.
The undissolved portion will then be found to consist of perfectly pure lactyl-para-
phenetidine.
The reaction takes place in accordance with the following equation
A Process for Obtaining the Lactyl Derivatives of Methyl-aniline,
Ethyl-aniline, Para-anisidine, and Para-phenetidine.
I, JAMES YATE JOHNSON of 47 Lincoln's Inn Fields in the County of London
Gentleman do hereby declare the nature of this invention (which has been
communicated to me from abroad by the Chemische Fabrik vorm. Goldenberg
Geromont & Co. of Winkel, Rheingau in the German Empire) and in what manner
the same is to be performed to be particularly described and ascertained in and
by the following statement:-
It is a well known fact that by starting operations with propionic acid, alpha-
hydro, oxypropionic acid, ie. lactic acid, may be obtained if the propionic acid be
first converted into propionic acid into which a halogen has been introduced, and
then the halogen in such an acid be replaced by hydroxyl by boiling with water, or
with solutions of alkaline hydrates, or alkaline carbonates.
With the assistance of this lactic acid synthetically obtained from propionic
acid, the process described in the Specification of Letters Patent No. 12166 of
30th June 1892 enables lactyl derivatives to be produced, which possess exactly
the same properties as those which are obtained by the employment of lactic acid
resulting from fermentation and described in the said Specification of the said
Patent No. 12166 of 1892.
My foreign correspondents have since ascertained that the lactyl derivatives of
the aromatic bases mentioned in that Patent may be obtained from propionic acid
direct, without the necessity of first couverting the propionic acid, into lactic acid.
It is well known that the halogen-propionyl derivatives of the primary and
secondary bases named, may be obtained by means of the chlorides or bromides of
the alpha-halogenysed propionic acids.

page_text: of paraphenetidine.
following equation :-
A reaction, then, immediately sets in according to the
NH.CO.CHBr.CH,
NH,HBr
After the paraphenetidine has been embodied in the solution, the ether is distilled
off and the residue extracted by means of cold water, whereby brom-hydrate of
para-phenetidine in solution is obtained, whilst alpha-brom-propionyl-para-
phenetidide remains undissolved, and may be crystallized out again from boiling
spirits of wine with a view to its further purification.
Similarly, the alpha-halogen-propionyl derivatives of the remaining bases are
obtained.
The following are the characteristic features of some of the alpha-halogen-
propionyl derivatives:―
Alpha-chlor-propionyl-methyl-anilide will crystallize out of hot ligroine in large
rhomboid tablets, its melting point being at from 51 to 52° Centigrade. It is
insoluble in cold water, but will dissolve readily in absolute alcohol, chloroform,
and benzol, and with difficulty in ether, petroleum-ether, and ligroine.
Alpha-chlor-propionyl-ethyl-anilide, and also alpha-brom-propionyl-ethyl-anilide
are oily. Both behave to solvents like alpha-chlor-propionyl-methyl-anilide.
Alpha-chlor-propionyl-para-anisidide crystallizes out of alcohol in prisms of
which the point of fusion is 110° Centigrade. In cold water petroleum-ether and
ligroine it will only dissolve with great difficulty, while it is readily soluble in
chloroform.
Alpha-brom-propionyl-para-phenetidide crystallizes in brilliant needles of a point
of fusion of 135° Centigrade. It is insoluble in water, dissolves with difficulty in
ether, and is readily soluble in heated alcohol.
These alpha-halogen-propionyl derivatives are remarkably proof against the
action of boiling water.
The halogen-propionyl derivatives are remarkably stable against the action of
boiling water by means of solutions of alkaline hydrates, these derivatives are
hydrolised, so that by means of these agents hydroxyl cannot be substituted for
halogen.
By the employment of solutions of carbonates of alkalies halogen metallic salts
may, indeed, be formed yet by this reaction pure products can be obtained only
with difficulty. The alpha halogenized propionyl derivatives of the aforesaid
aromatic bases may be readily converted into lactyl derivatives by boiling the
former with salts of carboxylic acids in aqueous or alcoholic solution. The
preferable agents for this purpose are the acetates of alkalies or alkaline earths.
With a view to accelerating the reaction and render it complete, it is advisable
to employ a quantity of acetate in excess. By raising the temperature, the
completion of the reaction may also be hastened.
.
.
20 kilogrammes of alpha-brom-propionyl-para-phenetidide is dissolved with from
12 to 20 kilogrammes (theoretically 10 kilogrammes) of crystallized acetate of
5 sodium in spirits of wine at 90 per cent. and the solution obtained is boiled in a
reflux apparatus, until a sample of the liquid precipitated with water and washed,
yields a product free from bromine.

page_text: Then the main portion of the alcohol employed is distilled off, the residue
-discharged into water and the precipitate washed with water until it is free from
bromine. The undissolved portion will then be found to consist of perfectly pure
lactyl-para-phenetidine.
The reaction takes place in accordance with the following equation
EXAMPLE 11.
21:35 kilogrammes of alpha chlor propionyl, para anisidide and from 15 to
20 kilogrammes of sodium lactate free from water (theoretically 11.2 kilogrammes)
are dissolved in alcohol at 90 per cent. and boiled in a reflux apparatus until a
sample of the liquid precipitated by means of water and washed is formed to be
lactyl para-anisidide free from chlorine. The rest of the process is performed as
described under the first example.
Having now particularly described and ascertained the nature of the said inven-
tion and in what manner the same is to be performed I declare that what I
claim is :-
The preparation of lactyl derivatives of methyl-aniline ethyl-aniline, para-
anisidine and para-phenetidine by heating the alpha halogenised propionyl
derivatives of the said base with salts of carboxylic acids in aqueous or alcoholic
. solution ether at normal pressure or at higher pressure.
Dated this 11th day of February 1896.
JOHNSONS & WILLCOX,
47 Lincoln's Inn Fields, London, W.C., Agents.