Improvements in the Manufacture of Spermine.
Year: 1890

page_text: The decision of the Comptroller-General, of the 17th day of April 1895, allowed,
under Section 18 of the Patents, &c. Act, 1883, an Amendment of this
Specification.
Date of Application, 29th Sept., 1890
Complete Specification Left, 19th June, 1891-Accepted, 25th July, 1891
PROVISIONAL SPECIFICATION.
Improvements in the Manufacture of Spermine.
1, WILHELM MAJERT of the Chemische Fabrik auf Aktien vormals E. Shering
of 11 and 12 Fennstrasse Berlin N. Germany Doctor of Chemistry do hereby
declare the nature of this invention to be as follows:-
Schreiner the chemist designates as "spermine" a base which he discovered in
human and animal sperm and which answers to the empirical formula C, H, N.
Ladenburg (see Bericht der Deutschen Chemischen Gesellschaft vol. xxi.
page 758) produced by heating hydrochlorate of ethylene diamine to a rather high
temperature a base which shewed the same composition as spermine and. which
agreed with all the chemical properties of spermine. Ladenburg considers spermine.
CH₂
as well as its base as ethylene-imine,
I
NH which in a watery solution
CH,
CH, -NH
CH
should be easily condensible to the piperazidine |
CH - NH - CH..
According to my invention I find that the latter formula appertains to the
material and that it can be easily produced by the treatment of
Diphenyl-
Ditolyl-
Dixylyl-
Dimesityl-
Dipseudocumyl-
Dinaphtyl-
one
Piperazidines which in each aromatic grain hold at least
consequently altogether two nitroso-nitro-,
chlorine-, bromine, or iodine groups in the ortho- or
para position to nitrogen with alkalies, alkaline earths
or mixtures of same.
Morley (see Bericht der Deutschen Chemischen Gesellschaft vol. xii. page 1795)
found that the dinitroso-di-ethylene-diphenyl diamine (dinitroso-diphenyl-piperazi-
dine) does not alter by treatment with boiling soda lye. But according to my
invention I have found the opposite. For dinitroso-diphenyl-piperazidine, when.
treated with alkali, alkaline earths or mixtures of same, divides up into one molecule
of piperazidine and two molecules of vitroso-phenol. My process forming the
subject of this invention and whereby a pure product is obtainable may therefore be
suitably carried out as follows:-

page_text: and about two to four parts by weight of twenty-five percental soda- or potash-lye
are distilled. The piperazidine passing over with the watery vapours is suitably
neutralized by means of hydrochloric acid (instead of which other acids such as
phosphoric acid or sulphuric acid may be applied). The saline solution is then
brought to crystallization by the application of heat. Instead of the soda or potash
1 may partly or wholly use alkaline earths, and of course also mixtures, of these
materials without departing from the essence of the invention. But it is advisable
when using alkaline earths to carry on the separation of the piperazidine in closed
vessels under pressure and at rather high temperature. In general I use water as
solvent for the alkalies or alkaline earths. When using less solvent alkaline earths
they are suitably mixed with the diluent to a milk. The hydrochlorate indicates
all the chemical properties of the ethylene-imine or spermine. It is applied to
therapeutic purposes.
The free base indicates the characteristic smell of sperm, is easily soluble in
water, not very soluble in soda lye and crystallizes from water into square tablets,
which glitter like glass. The aforesaid hydrochlorate salt crystallizes from watery
alcohol into long spears with branches. It contains water of crystallization. A
solution of iodide of potassium and bismuth produces in slightly acid and even very
weak solutions of the base a pomegranate coloured deposit consisting of small
microscopic leaves. The gold salt crystallizes into small yellow glittering leaves.
Picric acid solution produces a yellow deposit in the salt solutions.
Dated this 29th day of September 1890.
JENSEN & SON,
77, Chancery Lane, London, W.C., Patent Agents.
GODT HETE SPECIFICATION (AMENDED).
Improvements in the Manufacture of Spermine-that is to say, that
form of spermine which is represented by C, H. Nr.
CH, – NH – CH
-
CH, –NH
-
I, WILHELM MAJERT of the Chemische Fabrik auf Aktien vormals E. Shering
formerly of 11 and 12 Fennstrasse but now of 171 and 172 Müllerstrasse Berlin N.
Germany Doctor of Chemistry do hereby declare the nature of my said invention
and in what manner the same is to be performed to be particularly described
and ascertained in and by the following statement :--
Schreiner, the chemist designates as spermine a base which he discovered in
human and animal sperm and which answers to the empirical formula C, H, N.

page_text: Ladenburg (see Bericht der Deutschen Chemischen Gesellschaft vol. xxi.
page 758) produced by heating hydrochloride of ethylene diamine to a rather high
temperature, a base which shewed the same percentage composition as spermine and
which agreed with some of the chemical properties of spermine and which may be
taken to be a form of spermine. Ladenburg considers spermine meaning Schreiner's
CH₂
NH,
spermine above mentioned as well as its his base as ethylene-imine |_
CH
Ladenburg (see Bericht der Deutschen Chemischen Gesellschaft vol. xxi.
page 758) produced by heating hydrochloride of ethylene diamine to a rather high
temperature, a base which shewed the same percentage composition as spermine and
which agreed with some of the chemical properties of spermine and which may be
taken to be a form of sperinine. Ladenburg considers spermine meaning Schreiner's
CH₂
spermine above mentioned as well as its his base as ethylene-imine |
CH
NH,
which he states in a watery solution should be easily condensible to the piperazine
-
CH2 NH – CH.
-
I
or piperazidine, CH, - NH – CH,
-
According to my invention I find that the latter formula appertains to the
material and that it piperazine can be easily produced by the treatment of
dinitroso
Diphenyl-
Ditolyl-
Dixylyl
Dimesityl-
Dipseudoeumyl-
Dinaphtyl
Piperazine which in each aromatic nucleus hold at least
one-consequently-altogether at least two nitroso.;
nitro, chlorine, bromine, or iodine-groups-in-the
orthoor para position to nitrogen, with an alkali,
alkaline-earths or mixtures of-same-
Morley (see Bericht der Deutschen Chemischen Gesellschaft vol. xii. page 1795)
found that the dinitroso-di-ethylene-diphenyl-diamine (dinitroso-diphenyl-piper-
azine) does not alter by treatment with boiling soda lye. But according to my
invention I have found the opposite. For that dinitroso-diphenyl-piperazine when
treated with alkali, alkaline earths, or mixtures of same, divides up into one
molecule of piperazine and two molecules of nitroso-phenol. My process formning
the subject of this invention and whereby a-pure-produet which is a form of spermine
represented by C,H,N, piperazine is obtainable may therefore be suitably carried
out as follows.
10

page_text: and about two to four parts by weight of twenty-five percental soda- or potash-lye
are distilled. The piperazine passing over with the watery vapours is suitably
Eneutralized by means of hydrochloric acid (instead of which other acids such as
phosphoric acid or sulphuric acid may be applied). The saline solution is then
brought to crystallization by the application of heat.
Instead of the soda or potash I may partly or wholly-use-alkaline-earth-and-of
course also-mixtures of these-materials-without-departing from the essence-of-the
invention. But it is advisable when using alkaline earth to carry on the separation
of the piperazine-in-closed-vessels under pressure-and-at rather high-temperature:
In general I use water as solvent for the alkalies or-alkaline-earths: When using
less solvent alkaline earth they are suitably mixed with the diluent to a milk. The
hydrochloride indientes-some-of-the chemical properties of the ethylene imine-or
spermine. It piperazine is applied to therapeutic purposes.
The free base being the form of spermine hereinafter claimed and represented
by CH₁₂ piperazine indicates the characteristic smell of sperm, is easily soluble
in water, not very soluble in soda lye, and crystallizes from water into square
tablets which glitter like glass. The aforesaid hydrochloride crystallizes from
watery alcohol into long spears with branches. It contains water of crystallization.
A solution of iodide of potassium and bismuth produces in slightly acid and even
very weak solutions of the base a pomegranate coloured deposit consisting of small
'microscopic leaves. The gold salt crystallizes into small yellow glittering leaves.
Picric acid solution produces a yellow deposit in the salt solutions.
Having now particularly described and ascertained the nature of my said inven-
tion and in what manner the same is to be performed I declare that what I
'claim is :-
.1. The process for producing piperazine the form of spermine represented

page_text: by the formula C., H, NH - CH,
CH – NH – CH.
1
and in free condition has the smell of
-
spermine, dissolves with difficulty in soda lye, dissolves easily in water and
crystallizes from the latter in square tablets shining like glass.
Dated this 19th day of June 1891.
JENSEN & SON,
77, Chancery Lane, London, W.C., Patent Agents.