1,872,826
Patented Aug. 23, 1932
UNITED STATES
PATENT OFFICE
‘ >
WERNER SCHULEMANN, OF ELIBERFELD-VOHWINKEL, AND FRITZ SCHONH‘OFEB, OF
ELBERFELD, GERMANY, AND Alj'GI'l'ST WINGLER,
WESTFIELD, NEW JERSEY, AS
SIGNOBS TO WINTHROP CHEMICAL COMPANY, INC., OF NEW YORK, N. Y., A COR
PORATION OF NEW YORK
SOLUBLE SALTS OF ORGANIC BASES AND THE PROCESS OF PREPARING THE SAME
No Drawing. Application ?led July 7, 1928, Serial No. 291,136, and in Germany August 16, 1927.
The present invention concerns sparingly lent quantities of the hydrochlorides of thev
soluble salts of organic bases (the'term or organic bases or'of the alkaloids with the so
ganic bases is intended to include bases e._ g. dium salt of the aromatic acid in a suitable
aniino‘quinolines and basic compounds, like solvent, for example, water, the salt is precipi
r the alkaloids) with thefmethylene compounds tated as a sparingly soluble compound. In
of aromatic acids e. g. carboxylic- or sulfonic this manner not only neutral but also acid
acids and derivatives and substitution prod
salts can be obtained.
The following examples will illustrate our
ucts thereof.
The salts of organic bases with inorganic
invention :
Example 1.—221 parts by weight of 1'-(N 55
, acids often show the inherent great disadvan
’ tage of being deliquescent and oxidizable in methyl-N-diethyl-aminoethyl) - aminOJL-ami- >
the air. Salts of this kind are, moreover, nobenzene are dissolved in 4000 parts by
usually readily soluble in water and possess weight of
an unpleasant bitter taste, especially the salts
_ of the alkaloids, so that also on this account
n
2
’ their technical application, for example for
60
pharmaceutical purposes, is often rendered hydrochloric acid and combined whilst stir
impossible.
ring well with a ‘solution of 288 parts by
In‘accordance with the present invention weight of methylene disalicylic acid in 4000
,0 non-hygroscopic salts of organic bases of the parts by weight of
~
most varied kind, such as for example amino
65
quinoline, quinine, strychnine and the like,
which are extremely stable in the air are ob
2
tained by forming salts‘ of these substances
0 with the methylene compounds of aromatic caustic soda. An almost white salt having the
acids e. g. carboxylic- or sulfonic acids and.
probable formula:
COOK
OOOH
30'
Cl
40
HO
0H1
OH
75
derivatives and substitution products thereof, is precipitated, then ?ltered, washed repeat
such as for example, methylene dihydroxy-,B edly with water and dried. In contradistinc
naphthoic acid and methylene disalicylic acid. tion to the extremely deliquescent and readi
The salts of the said acids with‘ organic ly oxidizable hydrochloride it remains un
bases and alkaloids are generally yellowish changed in the air and is almost tasteless.
Example 2.—220 parts by weight of (N
products sparingly soluble in Water and taste
less; they are readily decomposed by acids or ethyl~N-diethyl-arninoethyl) -aniline are dis
alkalies into their components and are conse
solved in 4000 parts by weight of
quently well suitable for technical or pharma
ceutical use. They are soluble in alcohol, ace
tone, methyl alcohol.—-The manufacture of
2
these salts is‘ carried out in the customary hydrochloric acid and combined whilst stir
45
70
manner, for example, by combining equiva ring well with a solution of 388 parts by
80
85
2
1,872,826
weight of methylene di-B-hydroxynaphthoic thoic acid'as in Example 2 and yield a solid,
acid (compare Berichte der Dcutschen yellowish salt of the probable formula:
Chemischen Gesellschaft, vol. 34. (1901),
pagev 4162 in 4000 parts by weight of
\
'n
‘
OH
2
.
—COOH
'
'
H0
70
H000
'
caustic soda. The pale yellowish salt of the
probable formula :
H100
10
‘
'
'
/OH2\
75
N
OH
HO
COOH
HN-oHom-om-cm-N-(c111,),
B000
H:
i
which is almost insoluble in water and in 80
contradistinction to the deliquescent hydro
N
20
\CHz-CH2-N(C2Ha)2
which is precipitated, is ?ltered, washed re
chloride remains unchanged in the air and is
tasteless.
peatedly with water and dried. In contra
distinction to the hydrochloride which deli
quesces in the air, it is stable and tasteless.
ethylamino - ,8’- (G-methoxy-quinolyl-8-ami
no)-glycol-diethylether are treated with 388
Emample 3.—351 parts by weight of 1: 2
Example 6.—361 parts by weight of B-di
parts by weight of methylene-di-B-hydroxy
naphthoic acid as in Example 2 and yield a
aminobenzene are treated with 388 parts by solid yellowish salt of the probable formula: 90
dimethoxy - 4 - N - di - (diethylaminoethyl) -
25
weight of methylene di-,8-hydroxy-naphthoic
acid as in Example 2 and yield a solid salt of
/ CHI\
the probable formula:
OH
'
‘
OH2\
(00011
\
80
OH
H0
H10 0
—COOH
HOOC
0-011:
35
_
-
c1130
E
N-(CHz-CHTN(CIH5)I)2
H00
00
"00
o
96
.
100
which is soluble in water and in contradis which is sparingly soluble in water and in
tinction to the deliquescent hydrochloride contradistinction to the deliquescent hydro
remains unchanged in the air and is tasteless. chloride is stable »in the air and tasteless.
Example .4.——273 parts by weight of 6
Example 7.—174 parts by weight of 6- 105
are dissolved
quinoline are treated with 388 parts by with heating in 2000 parts by weight of
methoxy-N - (diethylaminoethyl) - 8-amino
methoxy~8-amino-quinoline
weight of methylene-di-,8-hydroxynaphthoic
45
acid as in Example‘ 2 and yield a. solid,
yellowish salt of the probable formula :v
2
hydrochloric acid and combined with 194
110
parts by weight of methylene-di-B-hydroxy
—OH
50
naphthoic acid dissolved in 2000 parts by
HO
weight of
—COOH
HOOC
>
-
n
116
2
CHaO
caustic soda. The yellow salt of the probable
N
a
55
H
formula :
120
,
N
which is sparingly soluble in water and in
contradistinction to the hygroscopic hydro
60
chloride remains unchanged in theair and is
CH
—OH
—OOOH
\
HO‘
H000
'
125
tasteless.
11.00 g
Example 5.—315 parts by weight of 6~meth
oxy - N - (a - diethylamino-8smethylbutyl) -8
aminoquinoline are treated with 388 parts by
65 weight of methylene di-,8-hydroxy-naph~
N
_
NH:
2 130
3"
1,872,826
which is precipitated, is sparingly soluble in sparingly soluble salts of bases, the step‘
water, stable in‘the air and tasteless.
which comprises allowing to react an or
ylene-di-?-hydroxyn_aphthoic acid are dis
naphthoic acid.
Example 8.—40 parts by weight of meth ganic base with methylene-di-B-hydroxy- ':
solved with warming in 2000 parts by weight
-
3. In the process for the manufacture of
of 111; n-caustic soda, the solution is ?ltered the salt of 6-methoxy-N-(a-diethyIaminO-S
and entered into a solution of 79 parts by methylbutyl)~8-aminoquinoline with meth
weight of quinine hydrochloride in water. ylene-di-B-hydroxy-naphthoic acid, the step
An almost colorless precipitate of the prob which comprises allowing to react these two
able formula:
10
products one with the other.
,
75
-
4. In the process for the manufacture of
the salt of 6-methoxy-N-(a-diethyIaminO-S
\
OH
methylbutyl)x-8~aminoquinoline with methyl- '
HO
.
15
COOK
-
(CmHu-Nzom
HOOC
_
ene-di~?-hydroxy-naphthoic acid, the step.
which comprises treating the hydrochloride 80'
of the base with an alkali metal salt rt the
is formed, which is ?ltered, washed with wa
ter and dried at a low temperature.
20
Thus is
acid in aqueous solution.
'
5. The new sparingly soluble salts of an
obtained a colorless, nearly tasteless powder, organic base with a methylene compound of 85
almost insoluble in water and containing an acid of the group consisting of aromatic,
sulfonic and carboxylic acids being gen-.
62.8% of quinine.
'
Q
It thus possesses a considerably higher erally whitish to yellowish powders having
25
quinine content than the quinine tannate not a sharp melting point, being soluble in
(also sparingly soluble and tasteless) which ethyl alcohol, acetone, methylalcohol and
being almost insoluble in water and being 0
according to its composition
valuable pharmaceutical products.
(Schmidt, Lehrbuch der Pharmazeutischen
30
.
6. The salt of 6-methoxy-N(a-diethylami
no - 8-methylbut l) '- 8 - aminoquinoline with
Chemie, 5th edition, 1910, vol. 2, page 1783) methylene-di-B- ydroxynaphthoic acid hav
only contains 30-32%.
- ing most probably the formula:
n L:
By using instead of the quinine other cin
chona or a solution of the total alkaloids of
cinchona bark the same process yields the
corresponding
35
methylene
di - B - hydroxy
naphthoic acid salts, which in appearance
and physical properties resemble that of
quinine.
Example .9.~—397 parts by weight of
strychnine nitrate are dissolved in water and
combined while stirring with a solution of
40
194: parts by weight of methylene di-B-hydroxynaphthoic acid in 2000 parts by weight
of
'
45
OH
HO
U
-—~COOH
100
HOOO
H200
N
HN.CH.OH2.CH2.CHz-N (021101 105
E:
being a solid yellowish salt almost insoluble '
in water, being tasteless and remaining un
changed in the. air.
2
110
7. The new sparingly soluble salts of an
caustic soda. The white salt precipitated of organic base derived from an aminoquinoline
with a methylene compound of an acid of
the probable formula:
the group consisting of aromatic‘ sulfonic
and carboxylic acids, being generally .whitish
115
melting point, being soluble in ethyl alcohol,
acetone, methylalcohol and being ,almost
1nsoluble in water and being Valuable phar
is ?ltered, washed and dried. In contradis maceutical products.
120
50
to yellowish powders having not a sharp
OH
HO
' (CglHn-oz-Nah
GOOH
HOOC
J
55
8. The new sparingly soluble salts of an
tinction to strychnine nitrate it is sparingly
S-aminoquinoline substituted in the amino
soluble in water and quite-tasteless.
group by a basic group with a methylene
1. In the process for the manufacture of compound of an acid of the group consisting
We claim :—
60
sparingly soluble salts of organic bases, the of aromatic sulfonic and carboxylic acids,
125
step which comprises allowing to react an‘ being generally whitish to yellowish pow
, organic base with a methylene compound of
an acid of the group consisting of aromatic
ders having not a sharp melting point, being
soluble in ethyl alcohol, acetone, methylalco
sulfonic and carboxylic acids.
hol and being almost insoluble in water and
'2. In the process for the manufacture of being valuable pharmaceutical products.
130
4
1,872,826
9. The new sparingly soluble salts of an
S-aminoquinoline substituted in the amino
group by a basic group with methylene-di
?-hydroxynaphthoic acid,‘ said products
being generally whitish to yellowish powders
having not a sharp melting point, being sol
uble in ethyl alcohol, acetone, methylalcohol
and being almost insoluble in water and
beng valuable pharmaceutical products.
10
10. The new salt of B-diethylan1ino-,B’
(6-methoxyquinolyl - 8 - amino) - glycol - di
thylether
with methylene-(1i - B - hydroXy
naphthoic acid having most probably the
formula :
'
--OH
HO
GOOH
HOOC
HaCO
N
5
N.CH2.CH2.0.CHg.CHz.O.CHz.C 2.N(C2H5)2
v
I
said product being a solid yellowish salt,
sparingly soluble in water, being stable in
the air and tasteless.
11. The new salt of strychnine with meth
ylene-di-,8-hydroxynaphthoic acid having
‘most probably the formula:
‘
CH2
/
OH
HO
- (C21Hn.01.N2):
C O OH
H0OC
said product'being a white salt sparingly
40
soluble in water and tasteless.
In testimony whereof we have hereunto set
our hands.
WERNER SOHULEMANN. [1,. s.]
45
50
55
60
65
FRITZ soHoNHoFER,
AUGUST WINGLER.
[LS-1
[1,. 8.]