Manufacture of Acetylleucomethylene Blue and of Acetylleu- coethylene Blue.
Year: 1898

page_text: PROVISIONAL SPECIFICATION.
Manufacture of Acetylleucomethylene Blue and of Acetylleu-
coethylene Blue.
I, OLIVER IMRAY, of Birkbeck Bank Chambers, Southampton Buildings,
Chancery Lane, in the County of London, Chartered Patent Agent, do hereby
declare the nature of this invention (as communicated to me from abroad by The
Farbwerke vormals: Meister Lucius and Brüning of Hoechst a/Main, in the
Empire of Germany, Chemical Manufacturers) to be as follows :-
:-
P. Ehrlich and A. Lippmann (Deutsche Med. Wochenschr. 1890 No. 23) proved
the anodyne property of methylene blue. The tinctorial power of the substance,
however, is an obstacle to its general application, so that it seems expedient to
possess a colourless derivative for medicinal purposes.
For this acetylleucomethylene blue is particularly suitable.
Bernthsen states (Ler. 16.1028. Annalen 230, 150) that he obtained this
substance by acetylisation of leucometylene blue.
But the body obtained by him differs so greatly in its essential properties from
that described hereafter, that for the present the compounds have to be considered
as different as hereinafter explained.
Bernthsen described his acetylleuco-methylene blue as an amorphous or gummy
mass, readily soluble in alcohol, ether and benzene, turning a darker blue
at 60° C.
The analysis did not coincide with the adopted formula. On the other hand the
compound obtained by my foreign correspondents is easily got in hard crystals; it
is soluble with great difficulty in hot alcohol and with difficulty in benzene,
remaining unchanged at a high temperature (150º C.).
The analysis corresponds exactly with the formula :-
Acetylleucomethylene blue is obtained in quantity if the reduction of the dyestuff
and the acetylisation of the leucobase is carried out in one operation, by working
as follows:
Into 25 parts by weight of methylene blue is poured a mixture of 25 parts by
weight of glacial acetic acid and of 75 parts by weight of acetic anhydride and
the mixture is gradually reduced by an addition of about 25 parts by weight of
zinc dust. On completion of the discolorisation the solution is boiled for from 1 to 2
hours. The product of reaction is precipitated from the filtrate by an addition of
water and recrystallised, best from hot glacial acetic acid. The given proportions
can vary within wide limits. In a similar manner acetylleacoethylene blue is obtained.
[Po dl

page_text: The method avoids the exceedingly tedious isolation of the sensitive leucomethylene
blue.
When in a pure state, acetylleucomethylene blue forms groups of hard needles,
melting at froin 179° to 181° C. and readily soluble in hot glacial acetic acid; they
are tasteless and are changed with elimination of methylene blue in an organism.
From the hydrochloric acid solution there separate on addition of ferric chloride
fine green needles of metallic lustre. The picrate of the acetylleuco-body is very
characteristic. When ether solutions of the components are mixed, the picrate is
precipitated as a very voluminous precipitate, which changes within a few minutes,
below the liquid into a heavy, fine crystalline brown powder and crystallises from
alcohol in greenish-brown glittering laminae having a melting point of 183° C.
Acetylleucoethylene blue (melting point from 179° to 180° C.) and its picrate closely
resemble the lower homologues.
Dated this 20th dow of June 1898
COMPLETE SPECIFICATION.
Manufacture of Acetylleucomethylene Blue and of Acetylleu-
coethylene Blue.
I, OLIVER IMRAY, of Birkbeck Bank Chambers, Southampton Buildings, Chancery
Lane, in the County of London, Chartered Patent Agent, do hereby declare the
nature of this invention (as communicated to me from abroad by The Farbwerke
vormals: Meister Lucius and Brüning, of Hoechst a/Main, in the Empire of Germany,
Chemical Manufacturers) and in what manner the same is to be performed,
to be particularly described and ascertained in and by the following statement :-
P. Ehrlich and A. Lippman (Deutsche Med. Wochenschr. 1890 No. 23) proved
the anodyne property of methylene blue. The tinctorial power of the substance,
however, is an obstacle to its general application, so that it seems expedient to
possess a colourless derivative for medicinal purposes.
For this acetylleucomethylene blue is particularly suitable.
Bernthsen states (Ler. 16. 1028. Annalen 230, 150) that he obtained this substance
by acetylisation of leucomethylene blue. But the body obtained by him differs
so greatly in its essential properties from that described hereafter, that the com-
pounds have to be considered as different, as hereinafter explained.
Bernthsen described his acetylleuco-methylene blue as an amorphous or gummy
mass, ready soluble in alcohol, ether and benzene, turning a darker blue
at 60° C.
The analysis did not coincide with the adopted formula. On the other hand the
compound obtained by my foreign correspondents is easily got in hard crystals; it
is soluble with great difficulty in hot alcohol and with difficulty in benzene,
remaining unchanged at a high temperature (150° C.). The analysis corresponds
exactly with the formula :-

page_text: dyestuff and the acetylisation of the leucobase is carried out in one operation, by
working as follows:
Into 25 parts by weight of methylene blue is poured a mixture of 25 parts by
weight of glacial acetic acid and of 75 parts by weight of acetic anhydride and
the mixture is gradually reduced by an addition of about 25 parts by weight
of zinc dust. On completion of the decolourisation the solution is boiled for from
1 to 2 hours. The product of reaction is precipitated from the filtrate by an
addition of water and recrystallised, best from hot glacial acetic acid. The
given proportions can vary within wide limits. In a similar manner acetylleuco-
ethylene blue is obtained.
The method avoids the exceedingly tedious isolation of the sensitive
leucomethylene blue.
When in a pure state, acetylleucomethylene blue forms groups of hard needles,
melting at from 179° to 181° C. and readily soluble in hot glacial acetic acid;
they are tasteless and are changed with elimination of methylene blue in an
organism.
From the hydrochloric acid solution there separate on addition of ferric chloride
fine green needles of metallic lustre. The picrate of the acetylleuco-body is very
characteristic.
When ether solutions of the components are mixed, the picrate is precipitated
as a very voluminous precipitate, which changes within a few minutes, below
the liquid into a heavy, fine crystalline brown powder and crystallises from
alcohol in greenish-brown glittering laminae having a melting point of 183° C.
Acetylleucoethylene blue (melting point from 179° to 180° C.) and its picrate
closely resemble the lower homologues.
Having now particularly described and ascertained the nature of this invention
and in what manner the same is to be performed, I declare that what I
claim is :-
1. The herein described manufacture of acetylleucomethylene blue or
acetylleucoethylene blue by reducing methylene blue or ethylene blue and
simultaneously subjecting it to the action of acetic anhydride.
2. Acetylleucomethylene blue and acetylleucoethylene blue manufactured as
above set forth.
Dated this 10th day of March 1899.