The Manufacture of New Compounds from Phenetidine and its Homologues.
Year: 1896

page_text: Date of Application, 19th Feb., 1896
Complete Specification Left, 19th Nov., 1896-Accepted. 19th Dec., 1896
PROVISIONAL SPECIFICATION.
The Manufacture of New Compounds from Phenetidine and its
Homologues.
A communication from abroad by LA SOCIÉTÉ CHIMIQUE DES USINES DU
RHÔNE, ANCT. GILLIARD P. MONNET & CARTIER, of Lyons, France,
Manufacturers.
1, GEORGE BELOE ELLIS of the Firm of J. C. Mewburn and Ellis of 55
and 56 Chancery Lane, in the County of London, Chartered Patent Agents, do
hereby declare the nature of this invention to be as follows:-
From phenetidine numerous derivatives have already been prepared by chemists,
which have found extensive employment in medicine on account of their anti-
pyretic and other remedial properties. These compounds, of which phenacetin
is typical, are formed by the substitution of one or both hydrogen atoms in
the amido group of phenetidine or its homologues by the radicles of carboxylic
acids.
The present invention relates to the preparation of a new series of phenetidine
compounds, analogous to phenacetin, but in which hydrogen is replaced by the
radicles of sulpho acids. These new compounds may be conveniently prepared by
the action of a molecular proportion of the chlorides of the respective sulpho
acids upon phenetidine and its homologues or their salts, in the presence of
alkalies.
For instance in order to prepare the para-toluene-sulpho-paraphenetidide, fifty
parts of hydrochloride of para-phenetidine are dissolved in 500 parts of water,
and fifty eight parts paratolnenesulphochloride, preferably dissolved in 500 parts
of toluene or other indifferent solvent, are added. Whilst the two solutions are
kept thoroughly mixed by an efficient mechanical stirrer, an aqueous solution
containing three molecular proportions of caustic soda is added very gradually,
several hours being occupied in this operation.
Under these conditions reaction takes place in the sense of the following
ouation

page_text: After allowing to stand the alkaline aqueous solution is drawn off and acidified
with dilute mineral acid, whereupon the para-toluene-sulpho-para-phenetidide
precipitated and may be purined by recrystallisation from alcohol. When pure
the product melts at about 105° C.
From the above example it is seen that the mono-sulpho-phenetidides are
distinguished from the corresponding compounds of carboxylic acids by an acidic
character, which enables them to form salts with alkalies. The sodium salt of
toluenesulphophenetidide being readily soluble in water is on this account specially
suitable for employment in medicine and the arts.
Dated this 19th day of February 1896.
J. C. MEWBURN & ELLIS,
55 and 56 Chancery Lane, London, Chartered Patent Agents.
The Manufacture of New Compounds from Phenetidine and its
Homologues.
A communication from abroad by LA SOCIÉTÉ CHIMIQUE DES USINES DU
RHÔNE, ANCT. GILLIARD P. MONNET ET CARTIER, of Lyons, France,
Manufacturers.
I, GEORGE BELOE ELLIS of the Firm of J. C. Mewburn and Ellis of 55
and 56 Chancery Lane in the County of London, Chartered Patent Agents,
'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:-
From phenetidine numerous derivatives have already been prepared by chemists
which have found extensive employment in medicine on account of their anti-
pyretic and other remedial properties. These compounds of which phenacetin
is typical, are formed by the substitution of one or both hydrogen atoms in
the amido group of phenetidine or its homologues by the radicles of carboxylic
acids.
The present invention relates to the preparation of a new series of phenetidine
compounds, analogous to phenacetin but in which hydrogen is replaced by the
radicles of sulpho acids. These new compounds may be conveniently prepared
by the action of a molecular proportion of the chlorides of the respective sulpho
acids upon phenetidine and its homologues or their salts, in the presence of
alkalies.
For instance in order to prepare the para-toluene-sulpho-para-phenetidide, fifty
parts of hydrochloride of para-phenetidine are dissolved in 500 parts of water and

page_text: fifty-eight parts of paratoluenesulphochloride, preferably dissolved in 500 parts
of toluene or other indifferent solvent, are added. Whilst the two solutions are
kept thoroughly mixed by an efficient mechanical stirrer an aqueous solution
containing three molecular proportions of caustic soda (or potash) is added very
gradually, several hours being occupied in this operation the time depending upon
the bulk of materials dealt with.
Under these conditions reaction takes place in the sense of the following
the product melts at about 105° C.
Similar condensation products may also be formed under the same conditions
not only by the action of benzene-sulphochloride, orthotoluenesulphochloride,
metatoluenesulphochloride, a- or -naphtalene-sulphochloride or other aromatic
sulphochlorides upon phenetidine but also by their action upon anisidine and higher
homologues of phenetidine.
In the same way the derivatives of the aromatic sulphochlorides react upon
phenetidine and its homologues. For instance by the action of ortho-nitro-para-
toluene-sulpho-chloride upon a molecular equivalent of para-phenetidine in the
presence of three molecular equivalents of caustic soda or potash, a condensation
product is obtained viz. :-ortho-nitro-para-toluene-sulpho-para-phenetidide, which
when precipitated from the alkaline liquors with acid, and recrystallised from
alcohol, melts at 128° C.
All these condensation products are more or less insoluble in water like
phenacetin, but the sulpho-phenetidides are distinguished from the corresponding
compounds with carboxylic acids by a more pronounced acidic character which
enables them to form salts with alkalies or other metals. The alkali salts of
toluene-sulpho-phenetidide and toluene-sulpho-anisidide being readily soluble
in water are on this account the more suitable for employment in medicine and
the arts. They may be prepared by dissolving the phenetidine compounds in
the theoretical quantity of boiling solution of caustic soda or potash and allowing
to crystallise.

page_text: Having now particularly described and ascertained the nature of this inven-
tion as communicated to me and in what manner the same is to be performed, I
declare that what I claim is :-
1. The manufacture of new compounds from phenetidine and its homologues by
replacing an amidogen hydrogen atom by the radicle of an aromatic sulpho acid,
substantially as described.
2. The manufacture of new compounds from phenetidine and its homologues by
the action of aromatic sulpho-chlorides upon phenetidine or its homologues or
upon their salts in the presence of an excess of caustic alkali, substantially as and
for the purposes described.
3. The manufacture of new compounds from phenetidine and its homologues by
the action of substituted aromatic sulphochlorides upon phenetidine or its
homologues or upon their salts in the presence of an excess of caustic alkali,
substantially as and for the purposes described.
4. As new products, para-toluene-sulpho-para-phenetidide, ortho-nitro-para-
toluene-sulpho-para-phenetidide and analogous condensation products of phenetidine
or its homologues with aromatic sulpho-chlorides or substituted aromatic
sulphochlorides.
5. As new products, the soluble alkali salts of the compounds claimed in 4.
this 19th day of November 1896.
J. C. MEWBURN & ELLIS,
55 and 56 Chancery Lane, London, Chartered Patent Agents.