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Патент USA US2403776

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Patented July 9, 1946
PhilipI .s. ' iWinnek,
~ amrnmrrnazme
Indianapolis, ta, assignor
‘I ‘to
American ,rGyanamid Company, :New .York,
:N. Y., a'corporation of Maine , ,
N‘o'Di'awingi Application August 25', 1943,
Serial No. 499,995
The present invention relates to a process for
Similarly, instead of the sodium salt of the
preparing 2-(N4-acylsulphanilamido) pyrazines.
N4-acylsulphanilamides I may use any other met
More particularly, the present invention relates
al salt, including those, such as the potassium,
calcium, lithium, copper, silver, and the like.
' to the process for producing 2-(N4-acylsulphanil
amido) pyrazines by reacting 2-chl0ropyrazine or '
} 'Therinvention will be described in greater de
tail in conjunction with the following speci?c
examples, which are merely illustrative of suit
able methods for preparing representative com
pounds and are not intended to limit the scope of
,2-brom0pyrazine with‘ an N‘lr-acylsulphanilamide
or metal salt thereof.
In carrying out the process of the present in
vention the N4-acy1su1pha'ni1amide0r metal salt
is heated with 2-chloropyrazine or 2-bromopyra 10 the invention.
zine in the presence of a basic substance and un
der substantially anhydrous conditions. During
2- (M-acetylsulphanilamidb) pyrazine
the course of the reaction hydrogen halide is lib- ,
erated and, where good yields are to be obtained,
it is desirable to provide a basic substance for 16
binding the liberated hydrogen halide. This can
be very readily accomplished by carrying the re
action out in the presence of a basic carbonate,
21.4 g. of ‘N4-acetylsulphanilamide, 13.8 g. of
bicarbonate, or hydroxide which‘ will neutralize
the hydrogen halide as formed, thus removing 20' anhydrous potassium carbonate, and 1 g. of 0011-.
per powder. are well mixed and placed in a three
it from the site of the reaction. Among the basic
necked‘ ?ask ?tted with a mechanical stirrer and
materials suitable for this purpose are potassium
re?ux condenser. 11.5 g. of'2-chloropyrazine are
carbonate, sodium carbonate, potassium bicar
‘added, and the mixture heated in an oil bath
bonate, sodium bicarbonate, potassium hydroxide,
(bath temperature, 2'20-240° C.) with‘ stirring for
and sodium hydroxide, etc.
four hours. The reaction mixture is cooled and
The temperature at which the reaction can be
250 cc. of water added. The mixture is stirred
carried out may be varied depending upon the
with decolorizing charcoal and ?ltered. On neu
basic substance employed and upon the N4-acyl-_
tralizing the ?ltrate with 6 N hydrochloric acid, a
sulphanilamide or metal salt employed. In gen
eral, the reaction proceeds smoothly when tem 30 brown precipitate separates. After standing in
the cold, the solid material is ?ltered off and
peratures of from about 150 to 300° C. are em
suspended in dilute ammonium hydroxide. The
ployed. The preferred operating temperature,
mixture is ?ltered, and the ?ltrate stirred with
when one of the reactants is N4-acetylsulphanil
' decolorizing charcoal. The solution is neutralized
amide, is within the range of from 200-to 240° C.
with dilute hydrochloric ‘acid, and the 2-(N4
While it may not be essential, it has been found,
acetylsulphanilamido) pyrazine separates as a
desirable to employ condensation catalysts, in
cluding certain powdered metals, such as plati
num, silver, and copper. In thisrespect copper
light brown solid with a melting point, 234-237“
C. The yield was 5.2 g.
is entirely satisfactory and is somewhat cheaper
than the other metals mentioned and for reasons 40
of economy is preferred.
In my preferred D1‘0cess I react N4-acetylsul
phanilamide with 2-chloropyrazine. These in
termediates are perhaps the cheapest andthose
that are most readily available, and, when the
reaction product is subsequently to be converted
into 2-sulphanilamido pyrazine, such reagents of
fer the greatest economical advantages. On the
other hand, when my process is employed for the
production of an N‘i-acylsulph‘anilamido pyrazine,
which is itself useful, it is clearly understood that
instead of Nf-acetylsulphanilamide, I may em
ploy any N4-acy1sulphanilamid0, including those,
such as the N4-pr0pi0ny1, -butyryl, -decoyl, -ben
zoyl, -furoyl, -and the like.
2-(N4-acetylsvulphanilamidod pyrazine
‘2.37 g. of sodium acetylsulph‘anilamide, 5.8 g.
of chloropyrazine, 1.38 g. of anhydrous potassium
carbonate, and 0.10 g. of copper powder are’ mixed
well and re?uxed with stirring on an oil bath
(150° C.) for three hours. The mixture softens
. and forms a gummy mass in the excess of chlo
ropyrazine. The gummy mass is dissolved in
water and the crude acetylsulphanilamido pyra
zinc is precipitated with dilute hydrochloric acid
--yield, 2.0 g. The product is puri?ed by dis
solving in dilute ammonia, treated with decoloriz
ing charcoal, and is precipitated with dilute hy
drochloric acid. The product is then recrystal
515 lized from 50% ethanol.
sisting of N4-acylsulphanilamides and metal salts
While 2-ch1oropyrazine is used in the above
thereof with a Z-halogenated pyrazine selected
examples, it is to be understood that 2-bromo
from the group consisting of 2-chloropyrazine
pyrazine can be used. The 2-chloropyrazine is
and Z-bromopyrazine, in the presence of a basic
preferred because it is more readily available than
substance and copper powder.
2-bromopyrazine at the present time. The prep
2. The. process of producing 2-(N4-acetylsu1
aration of-2-ch1oropyrazine is described in my
phanilamido) pyrazine which comprises heating
copending application, Serial No. 499,993, ?led
at a temperature within the range of 150° C. to
August 25, 1943. It is also to be understood that
300° C. a substance selected from the group con
sodium hydroxide or other‘ bases mentioned can
10 sisting of N4-acetylsu1phanilamide and metal salts
be used in place of potassium carbonate.
thereof with 2-ch1oropyrazine, in the presence of
The above descriptions and examples are in
a basic substance and copper powder.
tended to be illustrative only. Any modi?cation
3. The process of producing 2-(N4-acetylsu1
of or variation therefrom which‘ conforms to the
phanilamido) pyrazine which comprises heating
spirit of the invention is intended to be included
15 at a. temperature within the range of 150° C. to
within the scope of the claims.
300° C. the sodium salt of N4-acety1sulphanilamide
What I claim is:
1. The process of producing a 2-(N4-acylsul '- with 2-chloropyrazine in the presence of potas
sium carbonate and copper powder.
phanilamido) pyrazine which comprises heating
at a temperature within the range of 150° C. to
300° C. a substance selected from the group con
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