Патент USA US2403710код для вставки
Patented July 9, 1,946, 2,403,710 j UNITED".-SSTATE1S - w. ‘ _ 1 ' < ,2,4os,710i75 ~~ ', z-BnoMrYRAZrNnann M'Errnonorf " PBEPARINGSAME ,1 1 ' 1 ' P , Jaines‘K. Dixon, "Riverside, and J ohn M. Sayward, ‘ ' " ‘ Y - - ~ ; Stamford, Conn.,- asslgnorstoAmerican Cyan- v' 7 -' ' mid Company,:New York, N.,Y., a corporation .-ofMaine -.-* , > . , Drawing. 'Application'July 21,1944, ' _ i‘ ' ‘s ' Serial No..546,052 ' ' - '. r " 6Claims., (01. 2604-2395) 5 The present invention relates. to a newchemical compound,v 2_-brompyrazine and to a method of zine hydrobromide, as the case may’ be, are col lected in the cooler parts of the apparatus. - Upon preparing the same.-~: the‘addition of water- to the crystalline distillate, ; _ \ y a - 1 "' V, . ,We have discovered that Z-brompyrazine vcan 2¢brompyrazine separates as an oil. ‘be-prepared by heating~.together an .acid salt of pyrazine and bromine at temperatures up to about 1 . ~ - > - It is desirable, but'not necessary. to have pres ent ,at ‘ the ,itimeaof reaction an .inert solvent such 250° C. The formation of mono-brompyrazine in- ' as,‘carbon-‘tetrachloride; a Some of the advan-, this process involves, webelieve, the preliminary‘ tages of a solvent are-that it aidsin eliminating formation of a perbromide at relatively low tem peratures, room temperatures up to about 100° C., caking oi the pyrazine salt, makesthe reaction run smoother, and permits increasing the bromine usage to nearly 100% of theoretical without in creasing decomposition. The solvents which we followed by rearrangement at higher tempera tures to the corresponding acid salt of 2-brom pyrazine. The pure 2-brompyrazine may then can use in our process should have a boiling point be recovered by methods known to those skilled below that of brompyrazine and include such inert in the art. The formation of 2-brompyrazine by 15 solvents as carbon tetrachloride, chloroform, di our new process may be illustrated in the follow ing equations: oxane, benzene, and the like. ‘ The pyrazine acid salt found best suited for use in our process is pyrazine hydrochloride, HHa] which may be obtained by bubbling hydrogen /N\ 20 chloride through a solution of pyrazine in an or-' U ganic solvent. Pyrazine hydrochloride comes down as a nearly-white, ?uffy precipitate which can be separated by ?ltration. Other pyrazine acid salts such as pyrazine hydrobromide may, of HHal HHal N N\ ’ ——\ - N ~ 26 course, be used. 7 I The preparation of 2,-brompyrazine in accord _ ijBr + HBr - N ‘ ~ ance withour invention will now be illustrated by means of the following speci?c examples, which, it is understood, are given by way of illus 30 tration and are not intended to limit our process vto the particular reactants and reaction condi tions described therein. Example 1 Br, The compound z-brompyrazine (mono-brom pyrazine) is useful as an intermediate in the preparation of 2-aminopyrazine and in the prep aration of 2-sulfanilamidopyrazine. It will re act with para-acetylaminobenzenesulfonamide di 35 Into a 125 cc. stirred ?ask was placed 18 g. of pyrazine hydrochloride (80% pure==0.124 mol). Bromine 10.6 g. (0.066 mol) was added to the rectly to give 2 - p - acetylaminobenzenesulfona solid pyrazine slowly at about 50° 0., liberating midopyrazine, whereas the corresponding Z-chlor heat. The temperature was then raised to 150° 40 C.-165° C. for 1 hour, and then to 190° C. for 1 hour. At this \point vacuum was applied, through pyrazine does not react to any great extent. In carrying out our, invention, pyrazine hy drochloride or pyrazine hydrobromide is treated at ordinary room temperatures with 50 to 100% of the theoretical amount of bromine, thereby forming perbromide. a side tube and traps. White-to-yellow crystals 7 appeared in the traps while the reaction ?ask was kept'at 200°-215° C. for about 1.5 hours. The The perbromide is then 45 product, crude monobrompyrazine, separated as heated to at least 100° C_.,i'or about one to six an oil upon addition of water. hours. Under these conditions rearrangement occurs whereby the pyrazine ring is'brominated, releasing hydrogen bromide, and any solvent present is distilled off. The distillation system is water and. benzene from-the product gave an oil then put under a vacuum and the temperature maintained at 200° C. to about 250° C. for one 21.2 g. (0.132 mol) of bromine was added to’ half to about 4 hours, during which time 2-brom pyrazine distills from the reaction mass and crys tals o1 brompyrazine hydrochloride, or brompyra Distillation of which was identified as brompyrazine, Example 2 20.9 g. (80% pure—0.l43 mol) oi.’ pyrazine hydro. chloride-dissolved in 116 g. of carbon tetrachlo- V ride. Bromine addition was discontinued after 55 a half hour, when the charge began to darken 2,403,710 3 . 4 3. A method of preparing 2-brompyrazine whichcomprises mixing together bromine, an in (temperature about 32° 0.). Upon heating, hy drogen bromide came o-? at '70 to 80° C. Carbon tetrachloride was distilled off near 100'’ C. After one hour crystals began to appear in the con ert solvent and a halogen acid salt of pyrazine of the group consisting of pyrazine hydrochloride and pyrazine hydrobromide and heating the mix denser tubing (batlr 110° C.) . At15é~° C. carbon ture at a temperature up» to about 250°C. tetrachloride was all distilled off and hydrogen 4. A method of preparing Z-brompyrazine bromide evolution increased temporarily. During which comprises mixing together pyrazine hy 1.3 hours the bath was raised to 216° C. and more I drochloride and bromine and heating the mix crystals appeared. After 20 minutes at 216° C. a vacuum was applied for 25 minutes; consider 10 ture to a temperature at which Z-brompyrazine is distilled. able fog was carried through the traps. An oil, ' 5. A method of preparing 2-brompyrazine crude mono-brompyrazine, separated.‘ from the water used to rinse the tubing and traps, To - I which comprises the steps of adding bromine to a solution of pyrazine hydrobromide dissolved in prove the'structure of the compound as 2-brom .pyrazine, it was reacted with alcoholic ammonia 15 an inert solvent, thereafter raising the tempera ture of the reaction mixture to distill off the inert ‘solvent and continuing the heating under vacuum and gave a product which compared favorably with known sample of 2-aminopyrazine. Chem ical tests were employed to demonstrate the pres.-v and recovering therefrom z-brompyrazine hydro ence of vbromine and absence of chlorine, as com bromide. , 6. A method of preparing 2-brormpyrazine 20 pared with 2-ohlorpyrazine as a control. which comprises adding» pyrazine hydrochloride We claim: to a mixture of bromine and an inert‘ solvent and thereafter heating the mixture at a temperature up to about 250° C. for a period of from about which comp-rises adding bromine and an inert solvent to a halogen acid salt of pyrazine of the 25 one hour to ten hours whereby 2.-brompyrazine is formed and recovered as 2-bronrpyrazine hy group'consisting of pyrazine ‘hydrochloride and‘ 1. 2l-birompyrazine. - ' 2.‘ A method of preparing 2-brompyrazine pyrazine hydrobromide and heating the mixture to a temperature at which 2-brompyrazine is dis tilled. ' drochloride. ~ " ' JAMES'K. DIXON. JOHN M. SAYWARD.