NO317039B1

NO317039B1 - Process for the preparation of aminocyanacetamide

Info

Publication number: NO317039B1
Application number: NO19985775A
Authority: NO
Inventors: Ller Hans-Rudolf M; Heinrich Bollinger; Peter Schwaninger; Martin Kurz
Original assignee: Eprova Ag
Priority date: 1997-12-18
Filing date: 1998-12-10
Publication date: 2004-07-26
Also published as: PT924195E; HU9802955D0; CA2256251C; CN1224713A; AU9711798A; HU225196B1; DK0924195T3; NO985775L; RU2213728C2; DE59809481D1; CH692506A5; ES2206813T3; JP3452818B2; NO985775D0; CN1140504C; ZA9811569B; HUP9802955A3; JPH11310563A; EP0924195A1; CA2256251A1

Abstract

Preparation of aminocyanoacetamide (I) comprises reacting cyanoacetamide with nitrites at pH 2 to give nitrosocyanoacetamide, followed by catalytic hydrogenation.

Description

Den foreliggende oppfinnelse vedrører en teknisk anvendelig fremgangsmåte for fremstilling av aminocyanacetamid. The present invention relates to a technically applicable method for the production of aminocyanacetamide.

Aminocyanacetamid er et interessant mellomprodukt til fremstilling av f.eks. imidazoler, pyraziner, puriner eller pteridiner. Aminocyanacetamide is an interesting intermediate for the production of e.g. imidazoles, pyrazines, purines or pteridines.

Det er kjent forskjellige fremgangsmåte til fremstilling av aminocyanacetamid. Det skal derved spesielt nevnes Taylor et al som i J. Am. Chem. Soc, Vol 76, 1954, p 6080 beskriver en fremgangsmåte til fremstilling av aminocyanacetamid med utgangspunkt i hydroksyiminocyanacetamid ved hydrogenering med aluminiumamalgam, samt forskjellige fremgangsmåter til fremstilling av aminocyanacetamid med utgangspunkt i cyanoeddiksyreestere via aminocyaneddikester, såsom ifølge EP 0 342 616 hvorfra det er kjent å fremstille aminocyanacetamid ved nitrosering av en cyaneddiksyreester ved hjelp av et alkalinitritt, hydrogenering av den frem-stilte hydroksyiminocyaneddiksyreester med platina/hydrogen og etterfølgende frigjøring av aminocyanacetamid med vandig ammoniakk. På grunn av problemene med anvendelse av en kvikksølvkatalysator er fremgangsmåten til Taylor et al ikke teknisk anvendelig. Fremgangsmåter til fremstilling av aminocyanacetamid med utgangspunkt i cyaneddiksyreestere via aminocyaneddikester, såsom ifølge EP 0 342 616, beskriver teknisk omfattende fremgangsmåter som er basert på omstendelig omsetning av en cyaneddiksyre, som er beskyttet ved hjelp av en esterfunksjon, til en aminocyaneddikester og etterfølgende frigjøring av aminocyanacetamid. Various methods are known for the production of aminocyanacetamide. Special mention should therefore be made of Taylor et al as in J. Am. Chem. Soc, Vol 76, 1954, p 6080 describes a method for producing aminocyanacetamide starting from hydroxyiminocyanacetamide by hydrogenation with aluminum amalgam, as well as different methods for producing aminocyanacetamide starting from cyanoacetic acid esters via aminocyanoacetic esters, such as according to EP 0 342 616 from which it is known to prepare aminocyanoacetamide by nitrosation of a cyanoacetic acid ester using an alkali nitrite, hydrogenation of the produced hydroxyiminocyanoacetic acid ester with platinum/hydrogen and subsequent liberation of aminocyanoacetamide with aqueous ammonia. Because of the problems with the use of a mercury catalyst, the method of Taylor et al is not technically applicable. Processes for the production of aminocyanoacetamide starting from cyanoacetic acid esters via aminocyanoacetic acid esters, such as according to EP 0 342 616, describe technically comprehensive methods that are based on the extensive reaction of a cyanoacetic acid, which is protected by means of an ester function, to an aminocyanoacetic acid ester and subsequent release of aminocyanoacetamide .

Med fremgangsmåten ifølge oppfinnelsen kan det nå for første gang anvendes en teknisk anvendelig prosess til direkte fremstilling av aminocyanacetamid. With the method according to the invention, a technically applicable process can now be used for the first time for the direct production of aminocyanacetamide.

Fremgangsmåten ifølge oppfinnelsen er kjennetegnet ved at cyanacetamid omsettes med nitritter ved en pH-verdi på 2 til nitrosocyanacetamid, og at dette ved katalytisk hydrogenering omsettes til aminocyanacetamid. The method according to the invention is characterized by the fact that cyanoacetamide is converted with nitrites at a pH value of 2 to nitrosocyanoacetamide, and that this is converted to aminocyanoacetamide by catalytic hydrogenation.

De foretrukne utførelsene av fremgangsmåten er angitt i de uselvstendige kravene 2-14. The preferred embodiments of the method are indicated in the independent claims 2-14.

Cyanacetamid er et utgangsmateriale som er kommersielt tilgjengelig. Cyanacetamid nitrosieres med nitritter ved en pH-verdi på 2 til nitrosocyanacetamid. For nitrosieringen anvendes det fortrinnsvis et alkalinitritt, som fortrinnsvis tilsettes til en sur løsning eller suspensjon av cyanacetamid. pH-verdien holdes fortrinnsvis på 2 under nitrosieringen. Denne fremgangsmåte hindrer dannelse av større mengder biprodukter, minsker mengden nitrøse gasser som dannes og frembringer et godt sentrifugerbart produkt. Vanlige nitritter for nitrosieringen er alkalinitritter, fortrinnsvis natriumnitritt. Nitrittet anvendes i en mengde på 1-5 ekvivalenter, regnet av cyanacetamid, fortrinnsvis 1-2 ekvivalenter i forhold til cyanacetamid. Nitrosieringen foregår i sure medier, fortrinnsvis i konsentrerte, sterke mineralsyrer, spesielt saltsyre, ved en pH-verdi på 2. Reaksjonen foregår i en konsentrert løsning eller fortrinnsvis i en suspensjon ved temperaturer på mellom 0°C og 50°C, fortrinnsvis mellom 0°C og 5°C. Cyanoacetamide is a starting material that is commercially available. Cyanacetamide is nitrosated with nitrites at a pH value of 2 to form nitrosocyanacetamide. For the nitrosation, an alkali nitrite is preferably used, which is preferably added to an acidic solution or suspension of cyanoacetamide. The pH value is preferably kept at 2 during the nitrosation. This method prevents the formation of large amounts of by-products, reduces the amount of nitrous gases that are formed and produces a product that can be centrifuged well. Common nitrites for the nitrosation are alkali nitrites, preferably sodium nitrite. The nitrite is used in an amount of 1-5 equivalents, calculated by cyanoacetamide, preferably 1-2 equivalents in relation to cyanoacetamide. The nitrosation takes place in acidic media, preferably in concentrated, strong mineral acids, especially hydrochloric acid, at a pH value of 2. The reaction takes place in a concentrated solution or preferably in a suspension at temperatures of between 0°C and 50°C, preferably between 0 °C and 5°C.

Det derved oppnådde nitrosocyanacetamid omsettes ved en katalytisk hydrogenering til aminocyanacetamid. Hydrogeneringen foregår med hydrogen i nærvær av en katalysator. Egnete katalysatorer er fortrinnsvis edelmetallkatalysatorer, såsom platina, som er finfordelt i mengder på fra 1% til 20% på de vanlige bærermaterialer, såsom karbon, alu-miniumoksid, silisiumdioksid, bariumsulfat eller kalsiumkarbonat, eller platinaoksid. Fortrinnsvis anvendes som katalysator platina i en mengde på fra 2% til 10% på karbon. The thereby obtained nitrosocyanacetamide is converted by a catalytic hydrogenation to aminocyanacetamide. The hydrogenation takes place with hydrogen in the presence of a catalyst. Suitable catalysts are preferably noble metal catalysts, such as platinum, which is finely divided in amounts of from 1% to 20% on the usual carrier materials, such as carbon, aluminum oxide, silicon dioxide, barium sulfate or calcium carbonate, or platinum oxide. Platinum is preferably used as a catalyst in an amount of from 2% to 10% on carbon.

Hensiktsmessig anvendes katalysatoren i mengder på far 1% til 30%, regnet av nitrosocyanacetamidet, fortrinnsvis fra 2% til 10%, regnet av nitrosocyanacetamidet. The catalyst is suitably used in amounts of from 1% to 30%, calculated from the nitrosocyanacetamide, preferably from 2% to 10%, calculated from the nitrosocyanacetamide.

Hydrogeneringen foregår enten i vandige medier, såsom i vann, eller fortrinnsvis i overveiende ikke-vandige medier, såsom i vannblandbare alkoholer med lavere molekylvekt, så som valgt fra metanol og etanol, i vannblandbare karbonsyrer med lavere molekylvekt, valgt fra maursyre og eddiksyre, eller i tetrahydrofuran. For buffring av vandige hydrogeneringsløsninger kan det tilsettes litt natriumhydrogenftalat. Andre vanlige til-setningsstoffer, såsom jernsulfat for å undertrykke blå-syregasser som dannes, Raney-nikkel for å undertrykke kata-lysatorforgiftninger, osv., kan tilsettes til hydroge-neringsløsningen. The hydrogenation takes place either in aqueous media, such as in water, or preferably in predominantly non-aqueous media, such as in water-miscible alcohols of lower molecular weight, such as selected from methanol and ethanol, in water-miscible carboxylic acids of lower molecular weight, selected from formic acid and acetic acid, or in tetrahydrofuran. For buffering aqueous hydrogenation solutions, a little sodium hydrogen phthalate can be added. Other common additives, such as ferrous sulfate to suppress blue acid gases that are formed, Raney nickel to suppress catalyst poisoning, etc., may be added to the hydrogenation solution.

Anvendelsen av vannholdige katalysatorer skaper ved arbeid i ikke-vandige medier heller ikke problemer. De an-vendte katalysatorer kan etter endt reaksjon opparbeides igjen på enkel måte og anvendes for de etterfølgende reak-sjoner. The use of aqueous catalysts does not create problems when working in non-aqueous media either. The used catalysts can, after the reaction is finished, be worked up again in a simple way and used for the subsequent reactions.

Hydrogeneringen forgår ved et trykk på fra 1 bar til 100 bar, fortrinnsvis fra 1 bar til 10 bar, og ved temperaturer på mellom 0°C og 80°C, fortrinnsvis mellom 20°C og 50°C. Avhengig av trykk, temperatur, medium og katalysator-mengde kan hydrogeneringstiden variere mellom 30 minutter og 20 timer. The hydrogenation takes place at a pressure of from 1 bar to 100 bar, preferably from 1 bar to 10 bar, and at temperatures of between 0°C and 80°C, preferably between 20°C and 50°C. Depending on pressure, temperature, medium and catalyst quantity, the hydrogenation time can vary between 30 minutes and 20 hours.

Etter endt hydrogenering i vandige medier kan reak-sjonsløsningens pH-verdi senkes ved tilsetning av en syre, såsom eddiksyre. Dette hindrer dannelse av større mengder biprodukter. After completion of hydrogenation in aqueous media, the pH value of the reaction solution can be lowered by adding an acid, such as acetic acid. This prevents the formation of large amounts of by-products.

Oppfinnelsen vil i det etterfølgende bli belyst ved hjelp av eksempler. The invention will subsequently be illustrated by means of examples.

Eksempel 1 Example 1

Fremstilling av nitrosocyanacetamid. Preparation of nitrosocyanacetamide.

33,5 kg cyanacetamid i 78 1 vann ble anbrakt i en reaksjonsbeholder, og pH ble innstilt på 2,3 med 0,1 kg 37 prosentig saltsyre. Deretter ble en løsning av 28,7 kg 33.5 kg of cyanoacetamide in 78 l of water was placed in a reaction vessel, and the pH was adjusted to 2.3 with 0.1 kg of 37 percent hydrochloric acid. Then a solution of 28.7 kg was obtained

natriumnitritt i 45 1 vann tilsatt i løpet av 7 timer. Derved ble reaksjonsløsningens pH-verdi holdt på mellom 1,5 og 2,5 ved tilsetning av totalt 36 kg 37 prosentig saltsyre. Reaksjonsløsningens temperatur ble holdt på under 40°C. Av den klare, gulrøde løsning som oppstod under tilsetningen av natriumnitrittløsningen krystalliserte nitrosocyanacetamid ut allerede før avslutning av tilsetningen. Den gule suspensjon ble omrørt natten over ved romtemperatur og deretter avkjølt til 5°C. sodium nitrite in 45 1 of water added over 7 hours. Thereby, the reaction solution's pH value was kept at between 1.5 and 2.5 by adding a total of 36 kg of 37 percent hydrochloric acid. The temperature of the reaction solution was kept below 40°C. From the clear, yellowish-red solution that arose during the addition of the sodium nitrite solution, nitrosocyanacetamide crystallized out even before the addition was finished. The yellow suspension was stirred overnight at room temperature and then cooled to 5°C.

Den derved oppnåde hvite, tykke, grøtaktige krystal-lisasjonsmasse ble sentrifugert ved 5°C, vasket med vann og tørket ved 50°C i vakuum. Det ble oppnådd 33,9 kg nitrosocyanacetamid med et innhold på 99,1%, bestemt ved titrering. Identifiseringen av substansen foregikk ved hjelp av IR- og NMR-målinger. En sammenligning av disse spektre med en referansesubstans viste identiske verdier. The white, thick, mushy crystallization mass thus obtained was centrifuged at 5°C, washed with water and dried at 50°C in vacuum. 33.9 kg of nitrosocyanacetamide were obtained with a content of 99.1%, determined by titration. The substance was identified using IR and NMR measurements. A comparison of these spectra with a reference substance showed identical values.

Eksempel 2 Example 2

Fremstilling av nitrosocyanacetamid. Preparation of nitrosocyanacetamide.

250 ml 37 prosentig saltsyre (3 mol) ble anbrakt i en reaksjonsbeholder ved 0°C, og 171,6 g (2 mol) cyanacetamid ble tilsatt. Under omrøring ble det deretter inert dråpevis tilsatt en løsning av 156,0 g (2,26 mol) natriumnitritt i 600 ml vann i løpet av 5-7 timer. Temperaturen ble derved holdt på fra 0°C til 3°C. Det hvite krystallisat som derved ble dannet ble filtrert, vasket med vann og tørket ved 40°C i vakuum. Det ble oppnådd 142,6 g nitrosocyanacetamid med et innhold på 97,4%, bestemt ved hjelp av HPLC. Andelen cyanacetamid i det derved oppnådde produkt utgjorde 0,3%, bestemt ved hjelp av HPLC. 250 ml of 37 percent hydrochloric acid (3 mol) was placed in a reaction vessel at 0°C, and 171.6 g (2 mol) of cyanoacetamide was added. With stirring, a solution of 156.0 g (2.26 mol) of sodium nitrite in 600 ml of water was then added inert dropwise over the course of 5-7 hours. The temperature was thereby maintained at from 0°C to 3°C. The white crystallisate thus formed was filtered, washed with water and dried at 40°C in vacuum. 142.6 g of nitrosocyanacetamide were obtained with a content of 97.4%, determined by HPLC. The proportion of cyanoacetamide in the thus obtained product was 0.3%, determined by HPLC.

Eksempel 3 Example 3

Fremstilling av nitrosocyanacetamid. Preparation of nitrosocyanacetamide.

2,0 kg cyanacetamid og 1,8 kg natriumnitritt ble anbrakt i 4,3 1 vann. Etter oppvarming til 20°C ble det inert i løpet av 6 timer dråpevis tilsatt 2,4 1 37 prosentig saltsyre. Temperaturen ble derved holdt på fra 40°C til 50°C. Etter endt tilsetning ble den oppnådde suspensjon 2.0 kg of cyanoacetamide and 1.8 kg of sodium nitrite were placed in 4.3 L of water. After heating to 20°C, 2.4 1 37 percent hydrochloric acid was added dropwise over the course of 6 hours. The temperature was thereby maintained at from 40°C to 50°C. After the addition was completed, a suspension was obtained

omrørt ved fra 35°C til 40°C i ytterligere 40-50 minutter og deretter avkjølt til 10°C. stirred at from 35°C to 40°C for a further 40-50 minutes and then cooled to 10°C.

Det hvite krystallisat som ble dannet ble filtrert, vasket med vann og tørket ved 40°C i vakuum. Det ble oppnådd 2,5 kg nitrosocyanacetamid med et innhold på 90,7%. The white crystal that formed was filtered, washed with water and dried at 40°C in vacuum. 2.5 kg of nitrosocyanacetamide were obtained with a content of 90.7%.

De derved oppnådde 2,5 kg nitrosocyanacetamid ble oppvarmet til kokepunktet i 7,1 1 isopropanol og tilsatt 70 ml vann. Etter 2 timer ble suspensjonen filtrert klar. Den oppnådde rest ble vasket med 800 ml varm isopropanol. Etter konsentrering av filtratet til ca. 4 1 ble den gulaktige suspensjon oppbevart natten over ved -20°C. The 2.5 kg of nitrosocyanacetamide thus obtained were heated to the boiling point in 7.1 l of isopropanol and 70 ml of water was added. After 2 hours the suspension was filtered clear. The obtained residue was washed with 800 ml of hot isopropanol. After concentrating the filtrate to approx. 4 1, the yellowish suspension was stored overnight at -20°C.

Det oppnådde, hvite krystallisat ble filtrert og tørket ved 40°C i vakuum. Det ble oppnådd 2,0 kg nitrosocyanacetamid med et innhold på 100,0% og et spaltnings-produkt fra ca. 17 0°C. Andelen NaCl i det derved oppnådde produkt utgjorde mindre enn 0,5%. The white crystallisate obtained was filtered and dried at 40°C in vacuum. 2.0 kg of nitrosocyanacetamide were obtained with a content of 100.0% and a cleavage product from approx. 17 0°C. The proportion of NaCl in the thus obtained product was less than 0.5%.

Eksempel 4 Example 4

Fremstilling av nitrosocyanacetamid. Preparation of nitrosocyanacetamide.

5,15 kg cyanacetamid ble tilsatt til 7,5 1 37 prosentig saltsyre. Etter omrøring ble det deretter inert dråpevis tilsatt en løsning av 4,68 kg natriumnitritt i 1,8 1 vann i løpet av 3 timer. Temperaturen ble derved holdt på 5°C. Det oppnådde, hvite krystallisat ble filtrert, vasket med vann og tørket ved 40°C i vakuum. Det ble oppnådd 5,47 kg nitrosocyanacetamid med et innhold på 98,7%, bestemt ved hjelp av HPLC. Kloridinnholdet i det derved oppnådde produkt utgjorde 0,4%. 5.15 kg of cyanoacetamide was added to 7.5 1 37 percent hydrochloric acid. After stirring, a solution of 4.68 kg of sodium nitrite in 1.8 l of water was then added inert dropwise over the course of 3 hours. The temperature was thereby kept at 5°C. The white crystallisate obtained was filtered, washed with water and dried at 40°C in vacuum. 5.47 kg of nitrosocyanacetamide were obtained with a content of 98.7%, determined by HPLC. The chloride content in the thus obtained product was 0.4%.

Eksempel 5 Example 5

Fremstilling av aminocyanacetamid Preparation of aminocyanacetamide

31 g (0,27 mol) nitrosocyanacetamid ble i 700 ml metanol anbrakt i en stålautoklav og tilsatt 20 g platinakatalysator, 5% på karbon, med 50% vann. Etter spyling med nitrogen og hydrogen ble det hydrogenert ved romtemperatur og 2 bar hydrogentrykk i 14 timer. 31 g (0.27 mol) of nitrosocyanacetamide in 700 ml of methanol were placed in a steel autoclave and 20 g of platinum catalyst, 5% on carbon, with 50% water were added. After flushing with nitrogen and hydrogen, it was hydrogenated at room temperature and 2 bar hydrogen pressure for 14 hours.

Etter gassingen ble autoklavinnholdet frafiltrert og det oppnådde, lysegule filtrat konsentrert i vakuum inntil krystallisasjon. Krystallisatet ble oppslemmet i 250 ml isopropanol, filtrert og tørket ved 40% i vakuum. Det ble oppnådd 23 g svakt lysbeigt aminocyanacetamid med et innhold på 84,1%, bestemt ved hjelp av HPLC, og et dekompo-neringspunkt på ca. 120°C. After degassing, the autoclave contents were filtered off and the light yellow filtrate obtained was concentrated in vacuo until crystallization. The crystallisate was slurried in 250 ml of isopropanol, filtered and dried at 40% in vacuum. 23 g of slightly light beige aminocyanacetamide were obtained with a content of 84.1%, determined by HPLC, and a decomposition point of approx. 120°C.

Eksempel 6 Example 6

Fremstilling av aminocyanacetamid Preparation of aminocyanacetamide

Analogt med eksempel 5 ble hydrogeneringer gjennomført i følqende medier og med de angitte katalysatorer. - 1-) I eksemplene o-t ble den i foregående eksempel angitte katalysator anvendt. Opparbeidelsen av katalysatoren besto i vasking med vann/fortynnet saltsyre og etterfølgende tørking ved 130°C. Analogous to example 5, hydrogenations were carried out in the following media and with the stated catalysts. - 1-) In the examples o-t, the catalyst specified in the previous example was used. The processing of the catalyst consisted of washing with water/diluted hydrochloric acid and subsequent drying at 130°C.

Eksempel 7 Example 7

Fremstilling av aminocyanacetamid Preparation of aminocyanacetamide

200 g (1,77 mol) nitrosocyanacetamid ble i 2 1 vann anbrakt i en stålautoklav og tilsatt 49,95 g platinakatalysator, 5% på karbon. Etter spyling med nitrogen og hydrogen ble det hydrogenert i 8 timer ved 24°C og 2 bar hydrogentrykk. 200 g (1.77 mol) of nitrosocyanacetamide were placed in 2 l of water in a steel autoclave and 49.95 g of platinum catalyst, 5% on carbon, were added. After flushing with nitrogen and hydrogen, it was hydrogenated for 8 hours at 24°C and 2 bar hydrogen pressure.

Etter gassingen ble det tilsatt 117 ml eddiksyre til hydrogeneringsløsningen. Den klarfiltrerte, gulige hydro-generingsløsning ble konsentrert i vakuum ved 50°C inntil krystallisasjon. Krystallisatet ble tilsatt til 450 ml isopropanol og oppbevart natten over ved 0°C. Det oppnådde krystallisat ble filtrert, vasket med kald isopropanol og tørket ved 40°C i vakuum. Det ble oppnådd 136,7 g meget svakt lysegult aminocyanacetamid med et innhold på 99,7%, bestemt ved titrering og med et innhold av aminomalonsyre-diamid på 0,26%, bestemt ved HPLC. After gassing, 117 ml of acetic acid was added to the hydrogenation solution. The clear-filtered, yellow hydrogenation solution was concentrated in vacuo at 50°C until crystallization. The crystallisate was added to 450 ml of isopropanol and stored overnight at 0°C. The crystallisate obtained was filtered, washed with cold isopropanol and dried at 40°C in vacuum. 136.7 g of very faint light yellow aminocyanacetamide with a content of 99.7%, determined by titration and with an aminomalonic acid diamide content of 0.26%, determined by HPLC, were obtained.

100 g av det derved oppnådde, rå aminocyanacetamid ble løst i 240 ml 85°C varmt vann og raskt avkjølt til 0°C. Det derved oppnådde krystallisat ble frafiltrert, vasket med kald isopropanol og tørket ved 40°C i vakuum. Det ble oppnådd 7 9,2 g fargeløst aminocyanacetamid med et innhold på 100%, bestemt ved HPLC. 100 g of the crude aminocyanacetamide thus obtained was dissolved in 240 ml of 85°C hot water and rapidly cooled to 0°C. The resulting crystallisate was filtered off, washed with cold isopropanol and dried at 40°C in a vacuum. 79.2 g of colorless aminocyanacetamide were obtained with a content of 100%, determined by HPLC.

På analog måte ble 20 g av det oppnådde rå aminocyanacetamid løst i en blanding av 200 ml vann og 600 ml isopropanol ved 20°C og raskt avkjølt til 0°C. Det derved oppnådde krystallisat ble frafiltrert, vasket med en kald blanding av vann og isopropanol og tørket ved 40°C i vakuum. Det ble oppnådd 11,6 g fargeløst aminocyanacetamid med et innhold på 100%, bestemt ved HPLC. In an analogous manner, 20 g of the obtained crude aminocyanacetamide was dissolved in a mixture of 200 ml of water and 600 ml of isopropanol at 20°C and rapidly cooled to 0°C. The resulting crystallisate was filtered off, washed with a cold mixture of water and isopropanol and dried at 40°C in a vacuum. 11.6 g of colorless aminocyanacetamide were obtained with a content of 100%, determined by HPLC.

Det derved oppnådde produkt hadde ved romtemperatur en løselighet i metanol på 1,65 g/100 ml og i etanol på 0,85 g/100 ml. The thus obtained product had a solubility in methanol of 1.65 g/100 ml and in ethanol of 0.85 g/100 ml at room temperature.

Eksempel 8 Example 8

Fremstilling av aminocyanacetamid Preparation of aminocyanacetamide

8,5 kg platinakatalysator, 5% på karbon (ca. 50% vann) ble anbrakt i en inertisert hydrogeneringsreaktor og tilsatt 119 kg metanol. Til denne suspensjon ble det tilføyd 14,7 kg (130 mol) nitrosocyanacetamid. Etter spyling med hydrogen og nitrogen ble det hydrogenert i 11 timer ved 40-45°C og 2 bar hydrogentrykk. 8.5 kg of platinum catalyst, 5% on carbon (about 50% water) was placed in an inerted hydrogenation reactor and 119 kg of methanol was added. To this suspension was added 14.7 kg (130 mol) of nitrosocyanacetamide. After flushing with hydrogen and nitrogen, it was hydrogenated for 11 hours at 40-45°C and 2 bar hydrogen pressure.

Etter gassingen ble hydrogeneringsløsningen filtrert klar og filtratet natten over avkjølt til -18°C. After gassing, the hydrogenation solution was filtered clear and the filtrate cooled overnight to -18°C.

Krystallisatet som hadde dannet seg ble frafiltrert, vasket med kald etanol og tørket ved 40°C i vakuum. Det ble oppnådd 8,3 g svakt gulig aminocyanacetamid med et innhold på 99,2%, bestemt ved HPLC, og et innhold av nitrosocyanacetamid på 3,5%, bestemt ved HPLC. The crystallisate that had formed was filtered off, washed with cold ethanol and dried at 40°C in vacuum. 8.3 g of pale yellow aminocyanacetamide with a content of 99.2%, determined by HPLC, and a nitrosocyanacetamide content of 3.5%, determined by HPLC, were obtained.

Ved omkrystallisasjon analogt med eksempel 7 ble det oppnådd fargeløst aminocyanacetamid med et innhold på 100%, bestemt ved HPLC, og et innhold av nitrosocyanacetamid på under 0,1%, bestemt ved HPLC. By recrystallization analogously to example 7, colorless aminocyanacetamide was obtained with a content of 100%, determined by HPLC, and a content of nitrosocyanacetamide of less than 0.1%, determined by HPLC.

Claims

1. Process for the production of aminocyanacetamide, characterized in that cyanacetamide is reacted with nitrites at a pH value of 2 to nitrosocyanacetamide, and that this is converted to aminocyanacetamide by catalytic hydrogenation.

2. Method in accordance with claim 1, characterized in that for the production of the nitrosocyanacetamide, cyanacetamide is placed in an acidic medium to which the nitrite is added.

3. Process in accordance with claim 1 or 2, characterized in that during the nitrosation of cyanoacetamide to nitrosocyanoacetamide, the pH value is kept constant.

4. Method in accordance with claim 1, 2 or 3, characterized in that an alkali nitrite, preferably sodium nitrite, is used as nitrite.

5. Method in accordance with claim 1, 2, 3 or 4, characterized in that the nitrite is used in an amount of 1-5 equivalents, calculated from cyanoacetamide, preferably 1-2 equivalents, calculated from cyanoacetamide.

6. Method in accordance with claim 1, 2, 3, 4 or 5, characterized in that cyanoacetamide is converted in a concentrated solution or preferably in a suspension with nitrites to nitrosocyanoacetamide.

7. Method in accordance with claim 1, 2, 3, 4, 5 or 6, characterized in that cyanoacetamide is reacted at temperatures of between 0°C and 50°C, preferably between 0°C and 5°C, with nitrites to nitrosocyanacetamide .

8. Process in accordance with claim 1, characterized in that nitrosocyanacetamide is converted by catalytic hydrogenation in aqueous media to aminocyanacetamide.

9. Process in accordance with claim 1, characterized in that nitrosocyanacetamide is reacted to form aminocyanacetamide by catalytic hydrogenation in non-aqueous media, preferably in water-miscible alcohols with a lower molecular weight selected from methanol and ethanol, in water-miscible carboxylic acids with a low molecular weight, selected from formic acid and acetic acid, or in tetrahydrofuran.

10. Method in accordance with claim 9, characterized in that nitrosocyanacetamide is converted to aminocyanacetamide by catalytic hydrogenation in methanol.

11. Method in accordance with claim 1, 8, 9 or 10, characterized in that noble metal catalysts, such as platinum, which are finely divided in amounts of from 1% to 20% on common carrier materials are used as catalyst for the catalytic hydrogenation of nitrosocyanacetamide to aminocyanacetamide , such as carbon, aluminum oxide, silicon dioxide, barium sulfate or calcium carbonate, or platinum oxide.

12. Method in accordance with claim 1, 8, 9, 10 or 11, characterized in that platinum is used as catalyst for the catalytic hydrogenation of nitrosocyanacetamide to aminocyanacetamide in an amount of from 2% to 10% on carbon.

13. Method in accordance with claim 1, 8, 9, 10, 11 or 12, characterized in that the catalyst for the catalytic hydrogenation of nitrosocyanacetamide to aminocyanacetamide is used in amounts of from 1% to 30%, calculated from the nitrosocyanacetamide, preferably from 2% to 10%, calculated from the nitrosocyanacetamide.

14. Process in accordance with claim 1, 8, 9, 10, 11, 12 or 13, characterized in that the nitrosocyanacetamide is reacted by catalytic hydrogenation with hydrogen at from 1 bar to 100 bar, preferably at from 1 bar to 10 bar, and at temperatures of between 0°C and 80°C, preferably between 20°C and 50°C, to aminocyanacetamide.