Process for the Manufacture of Aceto-derivatives of the Simpler Aromatic Amines.
Year: 1897

page_text: COMPLETE SPECIFICATION.
Process for the Manufacture of Aceto-derivatives of the Simpler
Aromatic Amines.
A communication from abroad by W. J. MATHESON AND COMPANY LIMITED,
a Corporation organized under the laws of the State of New York, of
178, Front Street, New York City, New York, United States of America.
I, REGINALD WILLIAM JAMES, of the Firm of Fell and James, of 1, Queen
Victoria Street, in the City of London, Chartered 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 :-
The term aceto-derivatives of the simpler aromatic amines is herein used to
designate the class of crystalline compounds which is formed by the union of
acetic acid with the simpler amines of the benzene and naphthaline series, namely
acetanilide CH,NHC,H₂O, the acet-toluides CH,C,H,NHC,H,O, the acet-
xylides (CH3)2CH3NHC,H,O, and the acet-naphthalamides CH,NHC,H,O,
and their derivatives, the acet-radical replacing an atom of hydrogen in the amido
group of the amine.
Heretofore, these compounds have been made by heating strong concentrated
acetic acid and the desired aromatic amine, or by the reaction of acetic anhydride
or acetyl chloride with the amine. These methods of manufacture, however, are
expensive, because the concentrated acetic acid, the acetic anhydride and the
acetyl chloride are all difficult to obtain and therefore expensive, as compared with
the common acetic acid salts.
We have discovered that the various compounds of this class can be made
directly from the common acetic acid salts, thereby doing away with all the trouble
and expense of the manufacture and concentration of the acetic acid, acetic
anhydride or acetyl chloride, heretofore used, and so enabling us to produce them
in a much cheaper manner than that in which they have been produced up to the
present time.
Our newly discovered process of manufacture consists in replacing the acetic acid
radical of an acetic acid salt with another acid radical, and causing the acetic acid
radical thus liberated to unite with the desired aromatic amine, to form the aceto-
derivative thereof.
One specific method of carrying our invention into effect, and the one which we
consider as perhaps the most satisfactory, is as follows:-We bring together an
acetic acid salt (preferably the sodium or potassium salt) and a salt of the required
amine (the hydrochloride or sulphate being preferred). They readily react upon
each other, especially on the application of heat, the acid or negative radical of the
amine salt breaking up the acetic acid salt and uniting with its basic radical,
liberating at the same time the amine and acetic acid (and by the term acetic acid,
as hereinafter used, we mean the free acid or the nascent acid radical, whichever
form the said acid may take) and these unite somewhat less readily, and preferably
under the continued application of heat, to form the aceto-derivative of the amine,
and water. It is probable that the acetic acid and the amine, when first liberated,
unite to some extent at least, to form the acetate of the amine, but, be this as it
may, whatever the intermediate reactions and products, whether the two exist first
in mixture or are chemically united to a greater or less extent, the aceto derivative
and water are obtained as the final products. This latter reaction may be carried

page_text: out in the presence of the salt formed by the acid radical of the amine salt and the
basic radical of the acetic acid salt in the first reaction, or this newly formed salt
may first be removed by filtration or other suitable method.
It is important that all the material used should be as free from water as
possible, as the results will be most satisfactory if the reaction takes place in the
presence of a minimum quantity of water. It is best, therefore, to dehydrate the
salts, and this can easily be done by thoroughly drying them, a very simple
matter.
The relative proportions of the two salts used are, of course, governed by their
molecular weights, and will vary as either the amine salt or the acetic acid salt
used as a reagent therewith, is changed. It is sometimes desirable, however, to
have a slight excess of the acetic acid salt, or of acetic acid, in which case some
free acetic acid may be added, or a larger proportion of the salt may be used,
either with or without the addition of an acid, such, for example, as sulphuric acid,
to liberate the additional acetic acid required.
Taking aniline as a simple type of the aromatic amine and by way of illustration,
in practising our invention commercially, we first dry the salts and mix them
together in a suitable vessel, preferably an earthen-ware vessel with a reflex
condenser or similar contrivance attached thereto. A good relative proportion of
the dehydrated salts, if aniline hydro-chloride and the acetate of sodium are used,
is 129 parts by weight of the former to 82 to 84 parts by weight of the
latter. The mixture is then heated to a temperature in the neighbourhood of
125° Centigrade (although the degree of heat required to produce the best results
varies considerably according to circumstances) and it is best to further hasten the
first reaction by stirring; and under these conditions, it will take place in a very
short time. The mixture is then kept at practically the same temperature for a
period of some hours (say from twelve to twenty-four, although the length of time
required to produce the best results also varies largely according to circumstances
and especially the degree of heat employed) at the end of which it will be found
that the acetic acid and the aniline, liberated by the first reaction and left in
mixture or to some extent chemically combined, have for the greater part been
converted into acetanilide. The acetanilide is thereupon separated out or recovered
by pouring the mixture in its melted condition, or perhaps better after it has been
allowed to solidify by cooling into a vessel of cold water sufficient in quantity to
dissolve the various products or ingredients present which have not been converted
into acetanilide (including the salt formed by the base of the acetic acid salt and
the acid radical of the aniline salt by the first reaction, if this salt had not
previously been removed) the acetanilide being deposited, on cooling, in crystals
which can be removed and purified in the usual way; or it may be more convenient
to add to the mixture some solvent of acetanilide, such as wood spirit or methyl
alcohol or benzol, which will dissolve out the acetanilide and leave the other
ingredients, and then recover the acetanilide by distillation. In all cases, it is
desirable to recover the acetic acid and the aniline that were not converted into
acetanilide by some convenient method, such, for example, as distillation.
As above indicated, the length of time required for the operation depends
largely upon the amount of heat employed. The reactions will take place slowly
and more or less completely under ordinary temperatures but they are greatly
promoted, especially the final union of the acetic acid and the amine liberated by
the first reaction, and a maximum yield of the acet-derivative is obtained, by a
certain degree of additional heat. In commercial operations, a heat of about
125° Centigrade, as specified above, is the most satisfactory, for, while a materially
lower degree of heat will retard the reactions and yield a smaller amount of the
final product, a materially higher degree of heat is objectionable because it
necessitates doing the work under pressure and in vessels which are capable of
withstanding the pressure thus created and also the corroding effects of the acetic
acid so as not to be a source of danger, without increasing the amount of the
aceto-derivative obtained.

page_text: It is to be understood that in practising our invention we do not limit ourselves
to the use of the specific salts named, or to any particular salts of acetic acid and
the aromatic amines; nor do we limit ourselves to the use, in the first instance, of
an amine salt at all, as the same end may be attained by starting with the amine
itself and forming, as a part of the process, the amine salt which is to be used with
the acetic acid salt as above described, in any way, or by mixing the simple amine
with other materials capable of yielding acetic acid.
Thus, for example, by adding a concentrated acid, such, for instance, as
sulphuric acid, to an amine, we get the amine salt required for use with the acetic
acid salt and it is obvious that, in whatever order the various materials are brought
together, whether the acid is added first to the amine to form the amine salt and
the acetic acid salt is then mixed with the amine salt thus formed, or the acid is
first added to the acetic acid salt, or vice versa (in either of which cases a salt of the
acid used is formed and acetic acid liberated), and the amine is then added, or the
acid is added to a mixture of the acetic acid salt and the amine, the final result is
one and the same, namely, the production of a mixture containing acetic acid and
the amine (together with a salt of the base of the acetic acid originally used, and
with, perhaps, other ingredients or impurities) which are converted into the aceto-
derivative of the amine in the manner above described.
Or, as a further example, instead of using an acid as above indicated, we can
accomplish the same thing by the use of a salt, the basic or positive radical of
which is more volatile than the amine (the sulphate or the chloride of ammonium,
for instance, being examples of salts of this class, and the ones we prefer to use),
as the amine will replace this more volatile base under the conditions of beat and
dehydration we have pointed out above, thereby forming an amine salt and
liberating the volatile base of the salt used. And here, again, it is obvious that
the final result will be the same in whatever order the acetic acid salt, the amine
and the salt with the base more volatile than the amine are brought together,
although the intermediate reactions and products will vary; uamely, the volatile
base will be driven out by the amine and will escape at one stage or another, and
the aceto-derivative of the amine will be obtained as the final product.
Having now particularly described and ascertained the nature of this said inven-
tion and in what manner the same is to be performed, I declare that what I
claim is :-
:-
1. The above described method of producing the aceto-derivatives of the simpler
aromatic amines, which consists in making them directly from an acetic acid salt
by replacing the acetic acid radical of this salt with another acid radical, such
as a sulphuric acid radical, and causing the acetic acid radical thus liberated
to react finally with an aromatic amine to form the aceto-derivative thereof.
2. The above described method of producing acetanilide, which consists in
making it directly from an acetic acid salt by replacing the acetic acid radical of
the salt with another acid radical, such as a sulphuric acid radical, and
causing the acetic acid radical thus liberated to react finally with aniline to
form acetanilide.
3. The process of manufacturing the aceto-derivatives of the simpler aromatic
amines by the reactions of an acetic acid salt and an aromatic amine salt upon each
other, substantially as described.
4. The process of manufacturing acetanilide by the reactions of an acetic acid
salt and an aniline salt upon each other, substantially as described.
'וני מ
FELL & JAMES,
1 Queen Victoria Street, London, E.C., Agents for the Applicant.