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Патент USA US2411661

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Patented Nov. 26, 1946 '
‘ 1
' 2,411,661 ’ :
Henry Martin, Basel, Rudolf,‘Hirt,,Riehen,;and . Y 7
Alfred Staub, Basel, Switzerland, assignorslto ‘ '
vthe ?rm J. R. Geigy A. G., Basel, Switzerland,
acorporation of-Switzerl'and 7' I
I "
No-Drawing. - Application swim, 1945;_seria1,
In Switzerland" December- 23,
1 Claim. (01. 2664973)
‘It-has beenv found that valuable, llvaminoben
interaction ‘of the potassium vsaltof acetyl-sulf;
gene-sulfone-carbamiuacid derivatives are ob- '
'anilamide. with urea or with nitro-urea. ‘Ii-acet
tained-by causing sulfonamides, of the aromatic
ylaminobenzene-sulfoneeurea - 0 -methyl _- ether
series or their ‘salts respectively, which contain,
can be made from. 4-acetylaminobenzene<sulf0
chloride and lurea-O-methyl ether; By means
in 4-position, a nitrogen-containing group or a 5
substituent replaceable by such a group, to react
Withd‘eactive' carbamic acid" derivatives and con
.of hydrogen halide acids the 4-.acetylami-noben
zene-sulfone-urea is obtained which is converted
~into‘an amino group;
in the known manner into the amino compound.
All these interactions can‘, in the most cases,‘
verting‘ eventually the 4-positioned substituent
> On the, other hand, also possible to cause
be. carried, out directly or,/,if, necessary; by .the
use of solvents. or. dil'uen'ts'j,v Often any. addition
sulfone-halidesjof the‘ aromatic series contain
ing. in' "4'-positio_n,, a nitrogen-containing group
oi'condensation ‘agents or ‘catalysts may be of im
orva substituent replaceable by such a group to
react" with reactive vurea derivatives such‘ ‘as
ethers of .pseudo urea;;'t0 saponify thepseudo
' portance for. an' accelerated or smooth course of
the. reaction.‘ lThusit will‘ beadvantageous' to
urea ether v‘derivative, and to eventually convert
'thei‘iepositi'oned substituent into an amino group; ' ,
As reactive carbamic acid derivatives, which
may be ‘used for the condensation, especially the
work, e; g. for certainjinteractions, in the pres
ence .of. alkali- or earth.-alkali-salts or v-hydrox
ides or of otherijsuitable‘salts reacting in a basic
;manner or of, organictertiary bases,_ like trimeth- ’
ylamine, dimethylaniline, J pyridine “or formyl
anhydri-des'halides, esters or amides of carbamic 20' methylaniline, etc.
acid, are suitable, As anhydri'des of carbamic
IfYa'ccording’ to the above-mentioned reaction
acid may be enumerated cyanic, acid or its salts,
sequences. compounds are obtained‘ which con
whereas as halides the carbamic acid halides
tain imp-position to. the sulfonamide group other
~may bev employed; Asesters. the urethanesmay
substituent's than the aminogroup; for'example
be used, while as amidesurea'or the ethers of 25 the benzylamino, acyla'mino, nitro, azo, azo
its isoforin or nitro-urea aresuitable.
‘As; sulfonic: acid; amides or sulfonic acid halides
of thearomatic; series, which in 4-position con
tain a "nitrogen-containing group or a substitu
methine' or hydroxyl' groupphalogenh ‘the car
box'yl. group] or ‘derivatives I‘thereof or the‘ like,
usual known methods can be appliedjfor the
‘ formation of the free amino group, such'as're
ent replaceable by such a, group, may be under 30 duotion, saponi?cation, exchange of hydroxyl
stood benzene sulfonic acid derivatives possess
and halogen to the amino group, further decom
ing in Ill-position for example a free amino group,
position methods according to Hofmann and
a benzylamino group, an acylamino I group, a
Curtius and the like.
nitro, azo, azomethine, hydroxyl or carboxyl
group or derivatives thereof or a halogen atom.
A suitable method for the preparation of
‘4-amino-benzene-sulfone-carbamic acid deriva
tives consists for instance in causing 4-acety1
aminobenzene-sulfonamide to react with potas
sium cyanate thus giving 4-acetylaminobenzene
sulione urea and in subsequently saponifying this
product to the aminobenzene-sulfone urea.
When using 4-nitrobenzene-sulfonamide, instead}
a valuable
medicinal and therapeutical substance against
infection maladies.
The invention will now be described by Way of. r
the following examples, without being limited
thereto. The parts are by Weight.
Example 1
25 parts of v4-acetylaminobenzene-sulfamide
' are heated under reflux for 4 to 5 hours with 15
of 4-acetylaminobenzene-sulfonamide, . ll-nitro
parts of potassium cyanate, 95 parts of alcohol
benzene-sulfone-urea is obtained; ‘by reduction 45 and with 15 parts of Water. Thus the potassium
of this latter compound there will be obtained
salt of the 4-acetylamino-benzene-sulfo-urea is
4-aminobenzene-sulfone-urea. By condensation
obtained, the same being ?ltered oif, ‘dissolved in
of acetyl-sulfanilamide with carbamic acid chlo
ride the acetylaminobenzene-sulfone-urea is »
produced; also in this case the 4-nitrobenzene
sulfonamide may be used. When combining the
potassium salt of- acetyl-sulfanilamide with
urethane and heating this mixture there will
also be obtained 4-acetylaminobenzene-sulfone
urea. The same compound can be produced by 55
dilute caustic potash lye and. saponi?ed by a
slight heating. By acidi?cation the 4-amino
benzene-sulfo-urea is precipitated. It is ?ltered
and recrystallised from alcohol. Melting point‘
l_58°—160° C. under decomposition.
Example 2
10 parts of 4-nitrobenzene-su1famide in 30
parts of alcohol and 5 parts of water are heated
under re?ux for 8 hours with 4.5 parts of potas
sium cyanate. After cooling the potassium salt
of the 4-nitrobenzene-su1fo-urea is obtained,
which is ?ltered off and reduced in acatalytical
The thus obtained ll-aminobenzene
sulfo-urea is puri?ed by recrystallisation from al
cohol; M. P. l58°-160° C. under decomposition.
Ewample 3
Example 5
'71 parts of the sodium salt of acetyl-sulfanil
amide are heated to 100° C. with 30 parts of ure
thane until the splitting of! of alcohol is com
The resulting melt is dissolved in 2000
' plete.
parts of water and, after addition of 30 parts of
» concentrated caustic soda lye, maintained for 1
hour at 50° C. The ?ltered solution is neutral
ised with acetic acid, whereby 4-amino-benzene
10 sulfo-urea is separated in a crystalline form. Its
melting point is l58°—160° C.
Example 6
14 parts of urea, 50 parts of the potassium salt
ring this mixture at the said temperature,» a solu 15
of acetyl-sulfanilamide and 16 parts of glycol
tion of 10.5 parts of carbamic acid chloride in 20
parts of benzene is allowed to drop thereinto. I‘ monomethyl ether are heated to 100° C. until any
development of ammonia has ceased. The melt
Then the mixture is kept, while stirring for sev
is powdered after cooling, dissolved in dilute
eral additional hours, at 60°—65° C., whereupon
24 parts of the sodium salt of acetyl-sulfanilic
acid amide are suspended in 100 parts of benzene
and heated to 60°-65° C. While thoroughly stir
the benzene is distilled oil. The residue is dis 20 caustic soda lye, some .insoluble matters are ill
tered off and the 4-acetylaminobenzene-sulfo
solved in a cold dilute caustic soda lye, then freed
urea is saponi?ed. The é-aminobenzene-sulfo
‘from any insoluble matters and again precipi
tated by acidi?cation with acetic acid. The 4
acetylaminobenzene-sulfo-urea thus obtained is
'saponi?ed by heating its solution to 50° C. in a
dilute caustic soda lye and the p-aminobenzene
urea is obtained from the ?ltered solution by
acidifying the latter. M. P. 158°—160° C. under
Example 7
10 parts of 4-acetylaminobenzene-sulfamide
, sulfo-urea is precipitated by acidi?cation. M. P.
158°-160° C. under decomposition.
Example 4
and 10 parts of nitro-urea are dissolved in 100
parts of alcohol and treated with a solution of 6
30 parts of sodium carbonate in 20 parts of water.
After a boiling for 6-8 hours under re?ux the
20-parts of nitrobenzene-sulfamide are sus
alcohol is distilled off and the residue dissolved
ipended in 100 parts of dry dioxane. While cool
in caustic soda lye. By heating the acetyl group
' ing with ice, a solution of 15 parts of pyridine in
is split o? and the 4-aminobenzene-sulfo-urea
dioxane and a solution of 10 parts of carbamic
"acid chloride in 10 parts of dioxane are simul
taneously causedto drop into the said suspen
sion. Then the whole is heated to boiling for 4
precipitated by acidifying.
__hours and subsequently the‘ greatest part of diox
371,056 ?led on December 20, 1940.
What we claim is:
This application is a continuation-in-part ap
plication to our co-pending application Ser. No.
ane is distilled off. The residue is poured into di-~
'lute hydrochloric acid, whereby the raw nitro
benzene-sulfo-urea is precipitated. By dissolv
The condensation product of the formula
ingv the same in a dilute sodium carbonate solu
.tion and by ?ltration and subsequent acidi?ca
tion of the ?ltrate it can be recovered in a pure
_ form of melting point 1989-200" C.
By catalytical hydrogenation of the nitro com
‘pound there is obtained p-aminobenzene-sulfo
vurea melting at 158°-160° C. under decom
being a colorless compound of excellent thera
45 peutic properties andhaving the melting point
of 158°~160° C.
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