Патент USA US2403776код для вставки
2,403,776 Patented July 9, 1946 ;:u;m'reo » , _ a* 7'‘PREPARATION>j.2.4o_3,77.6'." OF 2-'(N4-ACYL'SUI'2PHA'NIL', ¢ ', ' 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, ~' ‘ ' 1 Serial No. 499,995 r r . 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 EXAMPLE 1 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. ' _ EXAMPLE 2 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. 2,403,776 3 4 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 20 . PHILIP S. WINNEK.