Year: 1891

page_text: Date of Application, 24th Mar., 1891
Complete Specification Left, 26th Nov., 189:-Accepted, 23rd Jan., 1892

page_text: salts are best formed by dissolving the glycocoll derivate in 20 parts of alcohol
at 96% and adding the calculated amount of concentrated muriatic acid to the
hot solution. In cooling the muriate salt separates mostly into fine needles.
Instead of alcoholic ammonia a watery ammonia solution may be applied but
with less success.
The reaction may also be produced by long standing in the cold
or by short heating to a higher temperature up to 110° C.
2. 10 kg. chlor- or brom-acetanilide or
10 "
"
"
acetparaphenetidine upon which
100% or 6% alcoholic or watery dimethylamine solution is poured is
heated 24 hours to 50° to 60° in a closed vessel. The alcohol or the water is then
distilled off and the residue put into as little water as possible which has been
slightly acidulated with hydrochloric acid. It is then filtered and the filtrate
thrown down by means of ammonia. The glycocoll derivate usually comes out
oily. The solvent is obtained crystallized by putting it in ligroine and cooling or
evaporating. Generally speaking in the first named process methyl-, dimethyl-,
ethyl- or diathylamines may be used instead of the ammonia.
3. 12.25 kg. muriate of glycocollmethylester or
13.95
10.05
32
"
"
2
"
together with,
glycocollethylester, or
glycocollamide are heated 5 or 6 hours to 130°-150° C.
18.6 kg. aniline or 214 kg. orthotoluidine or
214
24.6
29
دو
metatoluidine or 214 kg. paratoluidine or
orthoanisidine or 24.6 kg. metaanisidine or
24.6 paraanisidine or 27.4 kg. orthophenetidine or
27.4 metaphenctidine or 27-4 kg. phenetidine.
"
During the reaction methylalcohol, ethylalcohol or ammonia is evolved. When
the action is finished the unaltered aromatic amine is driven off by steam, and the
residue is dissolved in hot water slightly acidulated with muriatic acid; then
filtered and left to cool. To the cold solution-is added ammonia till a quite weak
alkaline reaction sets in. The liquid is filtered off from a small amount of separated
gum; the greater part of the aromatic glycocoll amine is thrown down by a
surplus quantity of ammonia. From the mother liquor a further quantity of the
aromatic glycocollamine is obtained by boiling down.
The hitherto unknown chloracetyl and bromacetyl derivates of aromatic amines,
and which are to be used in the above invention viz. —
a) chloracetmethylanilide
b) chloracctorthotoluide
c) chloracetmetatoluide
d) chloracetorthoanisidine
e) chloracetmetaanisidine
by the action of
) chloracetparaanisidine
g) chloracetorthophenetidine
h) chloracetmetaphenctidine
i) chloracetparaphenctidine
4) chloracetdiphenylamine
1 molecule chloracetic acid and 1 molecule phosphoric acid anhydride
a) 1 mol. methylaniline.
b) 1 mol. orthotoluidine
e) 1 mol. metatoluidine
d) 1 mol. orthoanisidine
e)
mol. metaanisidine
f) 1 mol. paraanisidine
g) 1 mol. orthophenetidine
h) 1 mol. metaphenetidine
i) 1 mol. paraphenetidine
k) 1 mol. diphenylamine
are obtained analogous to the chlorine acetanilide by the action of
1 mol. chloracetylchloride or
1 mol. bromacetylchloride upon
2 mol. orthotoluidine
2 mol. metatoluidine
2 inol. ortho-meta-para-anisidine
"
"
وو
phenetidine or

page_text: The hydrochlorate salts of the glycocoll products are of great therapeutic value
1 gr. of the hydrochlorate of glycocollparaphenetidine (hydrochlorate of
phenocoll) is certainly capable for instance of lowering fever temperature 2° C.
within half an hour while 2 gr. of antipyrine or 1 gr. of phenacetine produce the
same effect. Like the antipyrine it is also harmless to the human body even in
very large doses. It produces no collapse or cyanosis.
Dated this 24th day of March 1891. ·
JENSEN & SON,
77, Chancery Lane, London, W.C., Patent Agents.
COMPLETE SPECIFICATION.
Improvements in the Manufacture of Aromatic Glycocoll Derivates.
I, WILHELM MAJERT of 10 Madaistrasse Berlin in the Empire of Germany
Doctor of Philosophy 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 :-
By the action of alcoholic ammonia upon chloracetanilide at a temperature
of 100° C. Meyer obtained diglycolamid-acid anilide. According to Tommasi an
amorphous body is said to he produced by the action of alcoholic ammonia upon
chloracetanilide at 10° to 50° C. which body becomes soft at 65° C. and melts at
115° C. It is insoluble in water. Tommasi gives it the formula

page_text: (CH3)2]
3. Glycocoll-ortho-toluidine (CHC'H¸N"HCOCH,NH₂). It melts. at 66° C.,
crystallizes from water into long glittering needles. The diglycocoll-ortho-
toluidine melts at 155° C.
4. Glycocoll metatoluidine [CH (C'H¸)NшHсOCH,NH2]. It crystallizes
from water in which it dissolves with some difficulty, into long spears. Melting
point 74° C. The diglycocoll-metatoluidine melts at 220-221° C.
5. Glycocol paratoluide [CH(C'H,)NHCOCH,NH]. It crystallizes
into long water-containing needles, which melt at 94°-95° C. When free from
water of crystallization it melts at 107°. The diglycocoll paratoluide melts at
150.5° C.
6. Glycocoll-ortho-anisidine [CH.(OC'H¸)N"HCOCH,NH]. It crystallizes
into short broad needles and melts at 82° 83° C. Only very little diglycocoll-
ortho-anisidine is formed during the production.
7. Glycocoll-meta-anisidine [CH (OC'H¸)N"HCOCH,NH,]. It crystallizes
into small glittering leaves which melt at 96° C. The diglycocoll-meta-anisidine
melts at 116° C.
8. Glycocoll-para-anisidine [CH (OC'H3)NHCOCH,NH2]. It crystallizes
into needles and melts at 898 C. while the diglycocoll-para-anisidine melts at
142° C.
9. Glycocoll-ortho-phenetidine [CH (OCH)NH"COCH,NH,]. It dissolves
with some more difficulty than the anisidine derivate and melts at 66·5º C. Very
little of the diglycocoll derivate is formed.
10. Glycocoll-meta-phenetidine [CH.O'C₂H¸NHCOCH,NH,]. It melts at
92° C. Its diglycocoll-derivate melts at 130-131° C.
11. Glycocoll-para-phenetidine (CHO'CH¸NHCOCH₂NH₂). It crystallizes
with one mol. water into long needles which melt slowly at 95° C. When free
from water of crystallization it melts at 100-5° C. The several determinations of
the molecular weight of the acetic salt according to Roult gave 260 as a mean
instead of 254. A trial with chlorine gave for the muriate salt 15.77% instead
of 15.40% chlorine. Its diglycocoll derivate melts at 157° C.
12.
Dimethylglycocoll-para-phonetidine [CH(OCH)NHCOCH,N(CH₁),].
In the air it forms very deliquescent salts, dissolves with difficulty in water and
crystallizes from ether into small glittering leaves which melt at 50° C.
13. Glycocoll-diphenyl-amine [CH,N(CH)COCH,NH,]. It forms a muriate
salt which especially in saline solutions dissolves with difficulty. The free base
is easily soluble in water and in ligroine and melts at 38°-40°, while the diglycocoll
derivate dissolves with difficulty in water and melts above 240° C., while turning
brown.
The process is as follows:--
1. In 250 to 350 pounds of the strongest alcoholic ammonia are dissolved in a
wrought iron pressure vessel,
10 kg. chlor- or brom-acetanilide or
10
"
"
دو
"
10
"
"
"
29
acetorthotoluide or
acetmetatoluide or
10
"
"
"
acetparatoluide or
10
acetorthoanisidine or
"
39
"
10
22
""
""
"
10
39
52 . 3.
"
acetmetaanisidine or
acetparaanisidine or
10
"
"
"
"
acetorthophenctidine or
10
"
92
acetmetaphenetidine or
10
1
"
10
"
"
وو
acetparaphenetidine or
acetdiphenylamine,
and digested closed for 12 to 24 hours at 50° to 60° C. The ammonia which is to

page_text: be used agam for alcoholic saturation is then driven out at the return flow cooler.
The ammonia having been driven off, the alcohol is distilled off. The residue is
boiled with plenty of water. It is left to cool and the liquid is then separated
from the undissolved part by filtration. The filtrate is evaporated down and left to
cool. Ammonia is then added so as to produce a quite weak alkaline reaction.
This also causes the separation of a small amount of gummy substance. If now to
the clear filtrate is added the surplus ammonia, then it soon forms into a crystalline
mud of separated glycocoll-derivate. It is separated from the liquid and evaporated
down for eventually obtaining further glycocoll derivates therefrom. The
muriate salts are best formed by dissolving the glycocoll derivate in 20 parts
of alcohol at 96% and adding the calculated amount of concentrated muriatic
acid to the hot solution. In cooling the muriate salt separates mostly into fine
needles.
Instead of alcoholic ammonia a watery ammonia solution may be applied, but
with less success. The reaction may also be produced by long standing in the cold,
or by short heating to a higher temperature, up to 110° C.
2. 10 kg. chlor- or brom-acctanilide or
10° "
"
"
"
"
acetparaphenetidine upon which
100 7% or 6% alcoholic or watery dimethylamine solution is poured is
heated 24 hours to 50° to 60° in a closed vessel. The alcohol or the water is then
distilled off, and the residue put into as little water as possible which has been
slightly acidulated with hydrochloric acid. It is then filtered, and the filtrate
thrown down by means of ammonia. The glycocoll derivate usually comes out oily.
It is obtained crystallized by putting it in ligroine and cooling or evaporating the
solvent. Generally speaking in the first named process methyl-, dimethyl-, ethyl-
or diethylamines may be used instead of the amnionia.
The formation of the glycocoll derivates in many instances takes place already
when the watery or alcoholic ammonia solution or the solution of the above named
amines is left to stand, but the glycocoll derivates are formed more quickly by
heating to 100 or 110° C.
3. 12.25 kg. muriate of glycocollmethylester or
وو
13.95
10.05 ""
together with
"
"
"
"
glycocollthylester or
glycocollamide are heated 5 or 6 hours to 130°-150° C.
18.6 kg. aniline or 21.4 kg. orthotoluidine or
21.4 metatoluidine or 214 kg. paratoluidine or
"
24.6 orthonnisidine or 246 kg. metaanisidine or
59
24.6 paraanisidine or 274 kg. orthophenetidine or
"
27.4 "metaphenetidine or 274 kg. phenetidine.
During the reaction methylalcohol, ethylalcohol or ammonia is evolved. When
the action is finished the unaltered aromatic amine is driven off by steam, and the
residue is dissolved in hot water slightly acidulated with muriatic acid; then
filtered and left to cool. To the cold solution is added ammonia till a quite weak
alkaline reaction sets in. The liquid is filtered off from a small amount of separated
gum; the greater part of the aromatic glycocoll amine is thrown down by a
surplus quantity of ammonia. From the mother liquor a further quantity of the
aromatic glycocollamine is obtained by boiling down.
0
The hitherto unknown chloracetyl and bromacetyl derivates of aromatic amines,
and which are to be used in the above invention viz. —
a.) chloracetmethylanilide,
b.) chloracetorthotoluide,
c.) chloracetmetatoluide,
d.) chloracetorthoanisidine,
e.) chloracetmetaanisidine,
f) chloracetparaanisidine,
.) chloracetorthophenetidine,
h.) chloracetmetaphenetidine,
i.) chloracetparaphenetidine or
k.) chloracetdiphenylamine,

page_text: Third. The new chemical compounds obtained as described riz. :-
a) glycocollanilide,
b) dimethylglycocollanilide,
c) glycocollorthotoluide,
d)
glycocollmetatoluide,
e) glycocollparatoluide,
glycocollorthoanisidine,
y) glycocollmetaanisidine,
Dated this 26th day of November 1891.
h) glycocollparaanisidine,
i) glycocollorthophenetidine,
) glycocollmetaphenetidine,
1) glycocollparaphenetidine,
m) dimethylglycocollpara-
phenetidine, and
n) glycocolldiphenylamine.
JENSEN & SON.