DK158038B - METHOD OF PREPARING DI-N-PROPYLACETONITRIL - Google Patents
METHOD OF PREPARING DI-N-PROPYLACETONITRIL Download PDFInfo
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
Description
, DK 158038 B, DK 158038 B
Den foreliggende opfindelse angår en særlig fremgangsmåde til fremstilling af di-n-propylacetonitril, der har formlen ch3-ch2-ch2The present invention relates to a particular process for the preparation of di-n-propylacetonitrile having the formula ch3-ch2-ch2
^CH-CN ICH-CN I
ch3-ch2-ch2CH3-CH2-CH2
Di-n-propylacetonitril er et kendt produkt, der er af særlig interesse i forbindelse med fremstillingen af forbindelser med farmakologiske egenskaber. F.eks. kan di-n-propylacetonitril anvendes til fremstillingen af di-n-propylacetamid, der har yderst værdifulde neuro-psykotropiske egenskaber, jvf. fransk lægemiddelpatent nr. 2442 M.Di-n-propylacetonitrile is a known product which is of particular interest in the preparation of compounds having pharmacological properties. Eg. For example, di-n-propylacetonitrile can be used in the preparation of di-n-propylacetamide having extremely valuable neuro-psychotropic properties, cf. French Drug Patent No. 2442 M.
DK 158Ό38Β 2DK 158Ό38Β 2
Di-n-propylacetamid kan let og i fremragende udbytter af størrelsesordenen 83% fremstilles ud fra di-n-propylacetonitril ved hydrolyse af denne forbindelse, f.eks. ved hjælp af en vandig opløsning af 75 til 80$'s svovlsyre og ved en temperatur på mellem 80 og 130°C.Di-n-propylacetamide can readily and in excellent yields in the order of 83% be prepared from di-n-propylacetonitrile by hydrolysis of this compound, e.g. using an aqueous solution of 75 to 80 $ sulfuric acid and at a temperature between 80 and 130 ° C.
De sædvanlige fremgangsmåder til fremstilling af di-n-propylacetonitril er sædvanligvis komplicerede og nødvendiggør anvendelse af reaktanter, der er farlige for produktionspersonalet. F.eks. må man ved fremstillingen af di-n-propylacetonitril ud fra di-n-propylketon anvende natriumcyanid, der er et yderst giftigt produkt.The usual processes for preparing di-n-propylacetonitrile are usually complicated and require the use of reactants that are hazardous to production personnel. Eg. in the preparation of di-n-propylacetonitrile from di-n-propyl ketone, sodium cyanide, which is a highly toxic product, must be used.
Visse faser i fremstillingen indebærer endvidere hydrogenering, som altid er vanskelig at udføre i industriel skala.In addition, certain phases of manufacture involve hydrogenation, which is always difficult to perform on an industrial scale.
Nødvendigheden af at finde en industriel fremgangsmåde til fremstilling af di-n-propylacetonitril er således af stor betydning.Thus, the need to find an industrial process for the preparation of di-n-propylacetonitrile is of great importance.
Syntese af acetonitril, der er substitueret i α-stilling af to propyl-grupper, ud fra en ester af cyaneddikesyre, har hidtil kun været genstand for forsøg i de tilfælde, hvor hver af de to propylgrupper er en isopropylgruppe.Synthesis of acetonitrile substituted at the α-position of two propyl groups from an ester of cyan acetic acid has so far only been the subject of experiments in each of the two propyl groups being an isopropyl group.
I denne forbindelse kan nævnes de fremgangsmåder, der er beskrevet af Marshall i J. Chem. Soc. 2754-2761 (1930), af Brown et al. i J. Am. Chem. Soc. 77, IO83-IO89 (1955),og af Newman et al i J. Am. Chem. Soc. 82, 873-875 (I960).In this connection, the methods described by Marshall in J. Chem. Soc. 2754-2761 (1930), by Brown et al. in J. Am. Chem. Soc. 77, IO83-IO89 (1955), and by Newman et al in J. Am. Chem. Soc. 82, 873-875 (I960).
Disse fremgangsmåder, hvor man går ud fra en ester af·cyaneddikesyre, er karakteriseret ved en rækkefølge af tre eller fire helt bestemte stadier eller trin, nemlig: - en alkyleringsfase, der er fælles for alle tre fremgangsmåder, til opnåelse af en diisopropylcyaneddikesyreester, - en fase til fjernelse af den monoalkylerede ester, - en fase til hydrolysering af diisopropylcyaneddikesyreesteren i de af Marshall og Newman et al foreslåede fremgangsmåder, - og en decarboxyleringsfase, enten af diisopropylcyaneddikesyreester isn i· den af Brown et al foreslåede fremgangsmåde eller af diiso- propylcyaneddikesyrsii de af Marshall og af Newman et al. foreslåede f r emgangsmåd er.These processes, starting from an ester of cyan acetic acid, are characterized by a sequence of three or four definite stages or steps, namely: - an alkylation phase common to all three processes to obtain a diisopropylcyanacetic acid ester, - a phase for removing the monoalkylated ester, - a phase for hydrolyzing the diisopropylcyanacetic acid ester in the methods proposed by Marshall and Newman et al those of Marshall and of Newman et al. proposed f r approach is.
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Marshall fremstiller således diisopropylacetonitril ud fra en cyan-eddikesyreester ved behandling af en alkoholisk opløsning af denne ester med natrium og omsætning af denne blanding i adskillige timer med et overskud af isopropyliodid. Det monoalkylerede produkt fjernes ved hjælp af en 10$' s natriumhydroxidopløsning, og den ved denne metode opnåede rå dialkylester behandles derefter med en 35$'s kaliumhydroxid-opløsning i 16 timer. Efter at den opnåede diisopropylcyaneddikesyre er gjort sur, decarboxyleres den ved destillation i nærværelse af to gange dens vægt af smeltet kaliumhydroxid.Marshall thus produces diisopropylacetonitrile from a cyan acetic acid ester by treating an alcoholic solution of this ester with sodium and reacting this mixture for several hours with an excess of isopropyl iodide. The monoalkylated product is removed by a 10 $ sodium hydroxide solution and the crude dialkyl ester obtained by this method is then treated with a 35 $ potassium hydroxide solution for 16 hours. After the resulting diisopropylcyanacetic acid is acidified, it is decarboxylated by distillation in the presence of twice its weight of molten potassium hydroxide.
Brown et al får på deres side diisopropylacetonitril ved først at behandle en opløsning af cyaneddikesyreester i n-propanol indeholdende natrium-n-propylat med isopropyliodid under tilbagesvaling i 2 timer, efterfulgt af yderligere tilsætning af natrium-n-propylat i n-propanol og isopropyliodid. Reaktionsmediet opvarmes en gang til under tilbagesvaling i 3 timer, det monoalkylerede produkt fjernes ved hjælp af en 10$'s natriumhydroxidopløsning, og diisopropylcyaneddikesyreesteren afdestilleres derefter ad flere gange i nærværelse af to gange dens vægt af kaliumhydroxid.Brown et al, in turn, obtain diisopropylacetonitrile by first treating a solution of cyan acetic ester in n-propanol containing sodium n-propylate with isopropyl iodide under reflux for 2 hours, followed by further addition of sodium n-propylate in n-propanol and isopropyl iodide. . The reaction medium is heated under reflux again for 3 hours, the monoalkylated product is removed by a 10 $ sodium hydroxide solution and the diisopropylcyanacetic acid ester is then distilled off several times in the presence of twice its weight of potassium hydroxide.
Newman et al fremstiller diisopropylacetonitril ved omsætning af ethylcyanacetat med isopropyliodid i nærværelse af natriumethylat i ethanolisk medium under tilbagesvaling i 3 timer, efterfulgt af yderligere tilsætning af først natriumethylat. og derefter isopropyliodid og fornyet opvarmning af reaktionsmediet under tilbagesvaling i 3 ti-mer. Efter at der igen er tilsat natriumethylat og derefter isopropyliodid og er opvarmet i 2 timer under tilbagesvaling, vaskes det opnåede diisopropylerede derivat med en.15$'s kaliumhydroxidopløsning og hydrolyseres derefter ved hjælp af en alkoholisk opløsning af 35$' s kaliumhydroxid under tilbagesvaling i 26 timer, og den vundne diisopro-pylcyaneddikesyre opvarmes til l80-200°C i nærværelse af kobberpulver.Newman et al prepare diisopropylacetonitrile by reacting ethyl cyanacetate with isopropyl iodide in the presence of sodium ethylate in ethanolic medium under reflux for 3 hours, followed by further addition of first sodium ethylate. and then isopropyl iodide and reheating the reaction medium under reflux for 3 hours. After sodium ethylate and then isopropyl iodide are added again and heated for 2 hours under reflux, the obtained diisopropylated derivative is washed with a 15 $ potassium hydroxide solution and then hydrolyzed with an alcoholic solution of 35 $ potassium hydroxide under reflux. 26 hours, and the obtained diisopropylcyanacetic acid is heated to 180 DEG-200 DEG C. in the presence of copper powder.
På grund af den store lighed mellem diisopropylacetonitril og di-n-propylacetonitril i kemisk struktur er der nu foretaget forsøg på at fremstille sidstnævnte forbindelse under anvendelse af de ovennævnte fremgangsmåder, der hidtil har været anvendt til fremstillingen af diisopropylacetonitriler.Due to the great similarity between diisopropylacetonitrile and di-n-propylacetonitrile in chemical structure, attempts have now been made to prepare the latter compound using the aforementioned methods previously used in the preparation of diisopropylacetonitriles.
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Forsøg udført efter den af Marshall foreslåede teknik gav kun ubetydelige udbytter af rent di-n-propylacetonitril, nemlig af størrelsesordenen 20%, hvis hvert enkelt syntesemellemprodukt blev renset, og 35%, hvis alle mellemprodukter anvendtes i den rå tilstand; udbytterne er beregnet på basis af udgangscyaneddikesyreesteren. De ved denne fremgangsmåde fremstillede mellemprodukter var endvidere forurenede med urenheder, der forhindrede deres anvendelse i rå tilstand. Den ifølge Marshall eller Eewman et aL opnåede rå di-n-propylcyaneddikesyre viste sig således at være forurenet med 18 til 25% henholdsvis 32 til 34·% af et produkt, der synes at være en di-n-propylformamideddikesyreester.Experiments performed according to the Marshall technique yielded only negligible yields of pure di-n-propylacetonitrile, of the order of 20% if each synthesis intermediate was purified and 35% if all intermediates were used in the crude state; the yields are calculated on the basis of the starting cyan acetic acid ester. Furthermore, the intermediates produced by this process were contaminated with impurities which prevented their use in the crude state. Thus, according to Marshall or Eewman et al., Crude di-n-propylcyanacetic acid obtained was found to be contaminated with 18 to 25% and 32 to 34 ·%, respectively, of a product which appears to be a di-n-propylformamide acetic acid ester.
Den af Brown et al. foreslåede fremgangsmåde viste sig endvidere at være uegnet til fremstilling af di-n-propylacetonitril, da den nødvendiggør en dobbelt alkyl er ingsf ase. Det i ren form opnåede produkt svarede således til et udbytte på fra 28 til 4-4-% beregnet på udgangs-me thyl cyanacetatet.The one by Brown et al. Furthermore, the proposed process was found to be unsuitable for the preparation of di-n-propylacetonitrile as it requires a double alkyl ester phase. Thus, the product obtained in pure form corresponded to a yield of 28 to 4-4% based on the starting thyl cyanoacetate.
Den af Mewman et al. foreslåede fremgangsmåde, der nødvendiggør en tre-dobbelt alkyler ingsfase og er særlig tidsrøvende, gav endelig udbytter på omkring 4-0% rent di-n-propylacetonitril beregnet på basis af udgangscyaneddikesyreester. Det viste sig også, at hydrolysen af di-n-propylcyaneddikesyreesteren førte til en blanding af 10% di-n-propylcyaneddikesyre og 5% di-n-propylcyaneddikesyreamid.The one by Mewman et al. proposed process which requires a triple alkylation phase and is particularly time consuming finally gave yields of about 4-0% pure di-n-propylacetonitrile based on starting cyan acetic acid ester. It was also found that the hydrolysis of the di-n-propyl cyan acetic acid ester resulted in a mixture of 10% di-n-propyl cyan acetic acid and 5% di-n-propyl cyan acetic acid amide.
Fra J. Am. Chem. Soc. 38, 909-916 (1916) er det endvidere kendt at fremstille di-n-propylcyaneddikesyre ud fra cyaneddikesyreester, n-propyliodid og natriumholdig alkohol under dannelse af di-n-propyl-cyaneddikesyreester, som derpå hydrolyseres under anvendelse af kaliumhydroxid. Imidlertid er udbyttet af di-n-propylcyaneddikesyreester ringe, og indholdet af urenheder er stort.From J. Am. Chem. Soc. 38, 909-916 (1916), it is further known to prepare di-n-propyl cyan acetic acid from cyan acetic ester, n-propyl iodide and sodium-containing alcohol to form di-n-propyl cyan acetic ester which is then hydrolyzed using potassium hydroxide. However, the yield of di-n-propylcyanacetic acid ester is poor and the content of impurities is large.
Sammenfattende kan man sige, at alle de ovennævnte fremgangsmåder, når de anvendes på fremstillingen af di-n-propylacetonitril,ikke førte til det forventede resultat på grund af kompleksicitet og lang varighed, de i de forskellige trin opnåede urenheder, der nødvendiggjorde fjernelse af disse før de følgende trins gennemførelse, og de ringe udbytter af slut-di-n-propylacetonitrilet.In summary, all of the above-mentioned methods, when applied to the preparation of di-n-propylacetonitrile, did not produce the expected result due to complexity and long duration of the impurities obtained in the various steps which necessitated their removal. before carrying out the following steps and the low yields of the end-di-n-propylacetonitrile.
Det blev derfor nødvendigt at finde en anden, til fremstilling af di-n-propylacetonitril egnet fremgangsmåde, der opfylder følgende kvaliteter: 5Therefore, it became necessary to find another suitable process for the preparation of di-n-propylacetonitrile which satisfies the following qualities:
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- simpellied med hensyn til udførelse, - kort totalvarighed, - højt udbytte, - produktionsomkostninger, der er så lave som muligt, således at den med fordel kan anvendes i industriel skala.- simple in terms of execution, - short overall duration, - high yield, - production costs that are as low as possible so that it can be used advantageously on an industrial scale.
Ifølge den foreliggende opfindelse er det nu lykkedes at tilvejebringe en sådan industriel anvendelig fremgangsmåde til fremstilling af di-n-propylacetonitril, ved hvilken man går ud fra en cyaneddike-syreester.According to the present invention, it has now been possible to provide such an industrially useful process for the preparation of di-n-propylacetonitrile using a cyan acetic acid ester.
Efter fremgangsmåden ifølge opfindelsen fremstilles di-n-propylacetonitril. Fremgangsmåden er ejendommelig ved, at man sætter natrium-n-propylat i et n-propanol-medium til et reaktionsmedium, som har en temperatur mellem 45 og 55 °C, og som består af et cyanacetat med den alemene formelIn accordance with the process of the invention, di-n-propylacetonitrile is prepared. The process is characterized by adding sodium n-propylate in an n-propanol medium to a reaction medium having a temperature between 45 and 55 ° C and consisting of a cyanoacetate of the general formula
CNCN
//
H2C IIH2C II
\\
COORCOOR
hvori R betyder en alkylgruppe med fra 1-4 carbonatomer, og n-pro-pylbromid eller -iodid, hvorefter alkyleringsreaktionen finder sted under tilbagesvaling, derefter hydrolyserer den opnåede rå ester med en 10 til 20%'s natriumhydroxid- eller kaliumhydroxidopløsning ved en temperatur mellem 30 og 70°C, gør det opnåede salt surt med en stærk syre til dannelse af råt di-n-propylcyaneddikesyre og ved opvarmning til en temperatur mellem 140 og 190°C decarboxylerer denne til dannelse af di-n-propylacetonitril.wherein R represents an alkyl group having from 1-4 carbon atoms and n-propyl bromide or iodide, after which the alkylation reaction is refluxed, then hydrolyzes the crude ester obtained with a 10 to 20% sodium hydroxide or potassium hydroxide solution at a temperature between 30 and 70 ° C, the salt obtained acidifies with a strong acid to form crude di-n-propylcyanacetic acid and, when heated to a temperature between 140 and 190 ° C, decarboxylates it to form di-n-propylacetonitrile.
I alkyleringsfasen forbruges reaktanterne, når natrium-n-propylat i n-propanolmedium sættes til et reaktionsmedium bestående af cyaneddikesyreesteren og n-propylhalogenidet ved en temperatur mellem 45 og 55eC. Alkyleringsreaktionen kan udføres under tilbagesvaling i ca. 3 timer.In the alkylation phase, the reactants are consumed when sodium n-propylate in n-propanol medium is added to a reaction medium consisting of the cyan acetic ester and the n-propyl halide at a temperature between 45 and 55 ° C. The alkylation reaction can be carried out under reflux for approx. 3 hours.
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Hydrolysen af den rå di-n-propylcyaneddikesyreester sker fortrinsvis ved en temperatur mellem 60 og 70°C i løbet af et tidsrum på 3 timer i forholdet 1,25 til 2 mol hydroxid/mol ester, og den efterfølgende syrning udføres f.eks. med 36%'s saltsyre ved en temperatur, der er lidt lavere end 40°C.The hydrolysis of the crude di-n-propylcyanacetic acid ester is preferably carried out at a temperature between 60 and 70 ° C over a period of 3 hours in the ratio of 1.25 to 2 moles of hydroxide / mole of ester, and the subsequent acidification is carried out e.g. with 36% hydrochloric acid at a temperature slightly lower than 40 ° C.
Ifølge en alternativ metode udføres hydrolysefasen i nærværelse af en kvaternær ammoniumforbindelse, såsom trimethylcetyl-ammonium-bromid, benzyltrimethyl-ammoniumchlorid eller lauryltrimethylammo-niumbromid. Koncentrationen af den kvaternære ammoniumforbindelse kan ligge fra 0,005 mol til 0,1 mol/mol di-n-propylcyaneddikesyreester. Temperaturen ved hydrolysen og den til denne arbejdsgang nødvendige tid afhænger af den anvendte mængde kvaternære ammoniumforbindelse.According to an alternative method, the hydrolysis phase is carried out in the presence of a quaternary ammonium compound such as trimethylcetylammonium bromide, benzyltrimethylammonium chloride or lauryltrimethylammonium bromide. The concentration of the quaternary ammonium compound can range from 0.005 mol to 0.1 mol / mol di-n-propylcyanacetic acid ester. The temperature of the hydrolysis and the time needed for this process depend on the amount of quaternary ammonium compound used.
Ved en koncentration af kvaternær ammoniumforbindelse på 0,1 mol/mol ester forløber hydrolysen i løbet af 3 timer ved 30°C, medens arbejdsgangen ved en koncentration på 0,005 mol/mol ester vil være afsluttet i løbet af en time ved 60 til 65°C.At a quaternary ammonium compound concentration of 0.1 mol / mol ester, the hydrolysis proceeds over 3 hours at 30 ° C, while the workflow at a concentration of 0.005 mol / mol ester will be completed within one hour at 60 to 65 ° C.
Decarboxyleringsfasen udføres på den rå di-n-propylcyaneddikesyre ved en temperatur på mellem 140 og 190°0, fortrinsvis mellem 175 og 190°C.The decarboxylation phase is carried out on the crude di-n-propylcyanacetic acid at a temperature of between 140 and 190 ° 0, preferably between 175 and 190 ° C.
Ifølge en modifikation af denne arbejdsgang udføres decarboxyleringen af di-n-propylcyaneddikesyren i én kontinuerlig fase. Efter at den pågældende syre er bragt til en temperatur på 185-190°0, og decarb-oxyleringsreaktionen er startet, tilføres di-n-propylcyaneddikesyren kontinuerligt under samtidig fjernelse af den frigjorte carbondioxidgas og det dannede di-n-propylacetonitril.According to a modification of this operation, the decarboxylation of the di-n-propylcyanacetic acid is carried out in one continuous phase. After the acid in question is brought to a temperature of 185-190 ° and the decarboxylation reaction is started, the di-n-propylcyanacetic acid is continuously added while simultaneously removing the released carbon dioxide gas and the resulting di-n-propylacetonitrile.
Fremgangsmåden ifølge opfindelsen har ubestrideligt fordele i sammenligning med de fremgangsmåder, der er beskrevet i den ovenfor nævnte kendte teknik.The process of the invention has undeniable advantages over the methods described in the prior art.
For det første er det ved fremgangsmåden ifølge opfindelsen muligt at opnå betydelige udbytter af rent di-n-propylacetonitril, udbytter 7First, by the process of the invention, it is possible to obtain significant yields of pure di-n-propylacetonitrile, yields 7
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på mindst 80% beregnet på udgangscyaneddikesyreesteren, hvorimod det ved de i den kendte teknik foreslåede fremgangsmåder ikke har været muligt at opnå udbytter højere end 50% beregnet på samme udgangsester.of at least 80% based on the starting cyan acetic acid ester, whereas in the methods of the prior art it has not been possible to obtain yields higher than 50% calculated on the same starting ester.
Fremgangsmåden ifølge opfindelsen er endvidere utvivlsomt mere enkel end ovennævnte fremgangsmåder af Marshall, Brown et al. eller Newman et al. F.,eks. kan man ved fremgangsmåden ifølge opfindelsen udføre alkyleringsfasen ved én enkel arbejdsgang, hvor man blot anvender n-propylhalogenidet og natrium-n-propylatet.Furthermore, the process of the invention is undoubtedly simpler than the above methods by Marshall, Brown et al. or Newman et al. Eg. For example, in the process of the invention, the alkylation phase can be carried out in a single operation, using only the n-propyl halide and the sodium n-propylate.
Ben af Brown et al. foreslåede fremgangsmåde nødvendiggør derimod to successive tilsætninger af alkoholat og af halogenid, og tilsætningen af alkoholat og halogenid ved fremgangsmåden ifølge Newman et- a må udføres i tre successive arbejdsgange for de enkelte produkter.Ben by Brown et al. the proposed process, on the other hand, requires two successive additions of alcoholate and of halide, and the addition of alcoholate and halide by the method of Newman et al must be carried out in three successive workflows for the individual products.
Den til alkylerings- og hydrolysefasen nødvendige tid er også betydelig ved de kendte fremgangsmåder: mindst 8 timer for alkylerings-fasen ifølge den af Newman et al, foreslåede fremgangsmåde og 26 timer for hydrolysefasen ifølge samme forfattere.The time required for the alkylation and hydrolysis phase is also considerable in the known methods: at least 8 hours for the alkylation phase according to the method proposed by Newman et al and 26 hours for the hydrolysis phase according to the same authors.
Ved fremgangsmåden ifølge opfindelsen er det derimod muligt at udføre den tilsvarende alkylerings- og hydrolys'efase meget hurtigere end ved de kendte fremgangsmåder.In contrast, in the process of the invention it is possible to carry out the corresponding alkylation and hydrolysis phase much faster than in the known processes.
Den for hydrolysefasen nødvendige tid kan med fordel formindskes ved at arbejde i nærværelse af kvaternær ammoniumforbindelse, f.eks. tri-methylcetylammoniumbromid. Den kvaternære ammoniumforbindelse byder endvidere på den fordel, at faren for hydrolyse af nitrilfunktionen i di-n-propylcyaneddikesyreesteren formindskes.The time needed for the hydrolysis phase can advantageously be reduced by working in the presence of quaternary ammonium compound, e.g. tri-methylcetylammoniumbromid. The quaternary ammonium compound furthermore offers the advantage that the danger of hydrolysis of the nitrile function in the di-n-propylcyanacetic acid ester is reduced.
Decarboxyleringsfasen ved de kendte fremgangsmåder indebærer udover behovet for at forøge temperaturen endvidere en tilsætning af et supplerende produkt, enten kaliumhydroxid eller kobberpulver.In addition to the need to increase the temperature, the decarboxylation phase of the known processes also involves the addition of a supplementary product, either potassium hydroxide or copper powder.
Ifølge opfindelsen finder decarboxyleringsfasen sted ved simpel opvarmning af di-n-propylcyaneddikesyren.According to the invention, the decarboxylation phase takes place by simply heating the di-n-propylcyanacetic acid.
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En yderligere ulempe ved de i den kendte teknik foreslåede fremgangsmåder og nærmere bestemt ved alkyleringsfaserne, der forekommer i disse fremgangsmåder, vedrører genvindingen af opløsningsmiddel af reaktanterne, der ikke er omsat, og at biprodukterne, der dannes under omsætningen.A further disadvantage of the methods proposed in the prior art, and more particularly in the alkylation phases occurring in these processes, relates to the recovery of solvent of the unreacted reactants and to the by-products formed during the reaction.
Denne genvinding, der er temmelig vanskelig, når der anvendes natriumethyl at/ethanol eller natriummetbylat/metlianol, lettes ved anvendelse af natrium-n-propylat/n-propanol/ der giver bedre adskillelsesmuligheder ved afdestillation af det uomsatte n-propyl-halogenid, af etheren dannet under reaktionen og af alkoholen, som kan frigøres ved omforestering af cyaneddikesyreesteren med n-propanol.This recovery, which is rather difficult when using sodium ethyl at / ethanol or sodium metbylate / methianol, is facilitated by using sodium n-propylate / n-propanol / which provides better separation possibilities by distilling off the unreacted n-propyl halide by the ether formed during the reaction and of the alcohol which can be released by re-esterification of the cyan acetic ester with n-propanol.
Alle disse ved de i den kendte teknik foreslåede fremgangsmåder tilstedeværende ulemper forøger mængden af anvendt materiale, arbejdskraften og energiforbruget, hvilket fører til en tilsvarende forøgelse af produktionsomkostningerne.All of these by the disadvantages of the prior art methods increase the amount of material used, labor and energy consumption, which leads to a corresponding increase in production costs.
Blandt de ved de kendte fremgangsmåder forekommende ulemper skal man ikke mindst tage hensyn til tilstedeværelse af skadelige urenheder i de forskellige trin.Among the disadvantages of the known methods, the presence of harmful impurities in the various steps must be taken into account.
Disse urenheder, der er til stede i hver af fremgangsmådens faser, kan alene ødelægge den heldige udførelse af pågældende fremgangsmåde. Det er derfor nødvendigt at fjerne dem for hvert trin, hvilket imidlertid forøger arbejdsgangen til opnåelse af et anvendeligt mellemprodukt væsentligt, og dette er altid kostbart i industriel skala.These impurities present in each of the phases of the process can only destroy the successful execution of the process in question. Therefore, it is necessary to remove them for each step, which, however, significantly increases the workflow to obtain a usable intermediate, and this is always costly on an industrial scale.
De i den kendte teknik foreslåede fremgangsmåder foreskriver f.eks. fjernelse af det monoalkylerede produkt efter alkyleringsfasen, hvilket sker ved hjælp af 10%'s kaliumhydroxid.The methods proposed in the prior art prescribe e.g. removal of the monoalkylated product after the alkylation phase, which is done by means of 10% potassium hydroxide.
Yed alkyleringsfasen, der foreskrives indenfor rammerne af fremgangsmåden ifølge opfindelsen, er rensning af mellemproduktet di-n-propyl-cyaneddikesyreester unødvendig, idet den kan anvendes i sin rå form.In the alkylation phase prescribed in the process of the invention, purification of the intermediate di-n-propylcyanacetic acid ester is unnecessary as it can be used in its crude form.
Det har vist sig, at anvendelsen af alkyleringsreaktanterne efter fremgangsmåden ifølge opfindelsen i det væsentlige på grund af tilsætningen af natrium-n-propylat/n-propanol til et medium beståendeIt has been found that the use of the alkylation reactants according to the process of the invention is essentially due to the addition of sodium n-propylate / n-propanol to a medium consisting of
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9 af esteren med formlen II og n-propylhalogenidet har den særlige fordel, at man i maksimal grad undgår monopropylcyaneddikesyreester-dannelse; denne.er meget større, når n-propylhalogenidet sættes til cyaneddike syre ester/natrium-n-propylatblånding en. Denne monopropyl-cyaneddikesyreester kan eventuelt føre til dannelsen af valeronitril, der er særlig generende og derfor må fjernes.9 of the ester of formula II and the n-propyl halide has the particular advantage of avoiding to the maximum extent monopropylcyanacetic acid ester formation; this is much greater when the n-propyl halide is added to the cyan acetic acid ester / sodium n-propylate mixture. This monopropylcyanacetic acid ester may possibly lead to the formation of valeronitrile which is particularly troublesome and therefore must be removed.
Anvendelsen af alkyleringsreaktanterne efter fremgangsmåden ifølge opfindelsen indebærer, at indholdet af valeronitril i slut-n-propyl-acetonitrilet er. særdeles væsentligt formindsket, idet indholdet falder fra ca. 3,6% ved kendte fremgangsmåde til kun 0,3% ved fremgangsmåden ifølge opfindelsen.The use of the alkylation reactants according to the process of the invention implies that the content of valeronitrile in the final n-propyl acetonitrile is. very substantially reduced, with the content falling from approx. 3.6% by known method to only 0.3% by the method according to the invention.
Anvendelsen af natrium-n-propylat/n-propanol efter fremgangsmaden ifølge opfindelsen har endvidere vist sig at være meget mere fordelagtig end anvendelsen af natriumethylat/ethanol eller anvendelsen af natriummethylat/methanol som foreslået i fremgangsmåderne ifølge den kendte teknik.Furthermore, the use of sodium n-propylate / n-propanol in accordance with the process of the invention has been found to be much more advantageous than the use of sodium ethylate / ethanol or the use of sodium methylate / methanol as proposed in the methods of the prior art.
Det har således vist sig, at den rå di-n-propyleddikesyreesters indhold af monopropylcyaneddikesyreester, der efterfølgende fører til valeronitril, er forøget og endog kan ligge på fra 2 til 5%, hvis tilbagesvalingstemperaturen af reaktionsmediet er for lav under alky-leringsfasen, som det er tilfældet, når man anvender methanol eller ethanol.Thus, it has been found that the monopropylcyanacetic acid ester content of the crude di-n-propyl acetic acid, which subsequently leads to valeronitrile, is increased and may even range from 2 to 5% if the reflux temperature of the reaction medium is too low during the alkylation phase, this is the case when using methanol or ethanol.
Det har også vist sig, at anvendelsen af natriumethylat/ethanol-par-ret kan forøge dannelsen af en ikke ubetydelig mængde, d.v.s. omkring 1%, en ethyl-n-propylcyaneddikesyreester under alkyleringsfasen.It has also been found that the use of the sodium ethylate / ethanol pair can enhance the formation of a not insignificant amount, i.e. about 1%, an ethyl n-propylcyanacetic acid ester during the alkylation phase.
Som det endvidere tidligere er nævnt fører hydrolysen af det rå di-n-propylcyanacetat ifølge de af Newman et al. eller af Marshall foreslåede betingelser, d.v.s. ved behandling med 35%'s kaliumhydroxid i 16 timer til 26 timer, til dannelse af en rå di-n-propylcyaneddi-kesyre indeholdende fra 18 til 3^% af en urenhed, der synes at være di-n-propylformamidacetat. Dette sidste produkt giver ikke di-n-pro-pylacetonitril ved decarboxylering, men derimod di-n-propylacetamid, og må derfor fjernes.Furthermore, as previously mentioned, the hydrolysis of the crude di-n-propylcyanacetate according to those of Newman et al. or by Marshall proposed conditions, i.e. by treating with 35% potassium hydroxide for 16 hours to 26 hours, to give a crude di-n-propylcyanacetic acid containing from 18 to 3% of an impurity which appears to be di-n-propylformamide acetate. This last product does not give di-n-propylacetonitrile by decarboxylation, but di-n-propylacetamide, and must therefore be removed.
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Ved fremgangsmåden ifølge opfindelsen er denne ulempe ligeledes undgået, og man behøver ikke rense mellemproduktet af den rå di-n-propylcyaneddikesyre .In the process according to the invention, this disadvantage is also avoided and it is not necessary to purify the intermediate of the crude di-n-propylcyanacetic acid.
Under de til grund for den foreliggende opfindelses liggende forsøg er det forsøgt at forene visse fasekarakteristika ved fremgangsmåden ifølge opfindelsen med karakteristika ved de tidligere nævnte hidtidige fremgangsmåder.During the experiments underpinning the present invention, it has been attempted to reconcile certain phase characteristics of the process of the invention with characteristics of the previously mentioned methods.
Dialkyleringsfasen ved fremgangsmåden ifølge opfindelsen kombineret med et decarboxyleringstrin af di-n-propylcyaneddikesyre ved smeltning med to gange syrens vægt af 85%'s kaliumhydroxid ved en temperatur på mellem 190 og 360°C ifølge den af Marshall foreslåede fremgangsmåde gav imidlertid f.eks. kun 11% di-n-propylacetonitril beregnet på den anvendte cyaneddikesyreester. Ved denne metode blev det meste di-n-propylcyaneddikesyre omdannet til di-n-propylacet-amid og di-n-propyleddikesyre.However, the dialkylation phase of the process according to the invention combined with a decarboxylation step of di-n-propylcyanacetic acid by melting twice the weight of 85% potassium hydroxide at a temperature between 190 and 360 ° according to the method proposed by Marshall, for example. only 11% di-n-propylacetonitrile calculated on the cyan acetic acid ester used. By this method, most di-n-propylcyanacetic acid was converted to di-n-propylacetamide and di-n-propylacetic acid.
En variation af den af Marshall foreslåede decarboxyleringsfremgangsmåde er også udført med di-n-propylcyaneddikesyre, opnået efter fremgangsmåden ifølge opfindelsen, og to gange syrens vægt af 98%'s natriumhydroxid. Denne blanding gav efter 2 1/4 times destillation ved 370'°0 kun 38,3% di-n-propylacetonitril beregnet på anvendt di-n-propylcyaneddikesyre .A variation of the decarboxylation process proposed by Marshall is also carried out with di-n-propylcyanacetic acid, obtained according to the process of the invention, and twice the weight of the acid of 98% sodium hydroxide. This mixture gave only 38.3% of di-n-propylacetonitrile, based on used di-n-propylcyanacetic acid, after 2 1/4 hours of distillation at 370 °.
Den efter fremgangsmåden ifølge opfindelsen opnåede methyl-di-n-propylcyaneddikesyre blev endvidere destilleret i nærværelse af kaliumhydroxid efter Brown et al.’s fremgangsmåde.The methyl di-n-propylcyanacetic acid obtained according to the invention was further distilled in the presence of potassium hydroxide according to Brown et al.'s method.
Ved anvendelse af den dobbelte vægtmængde af 97,7%*s kaliumhydroxid som af ester og opvarmning til 380°0 i mindst 2 1/4 time fik man kun 28,4% rent di-n-propylacetonitril, beregnet på udgangscyanacetatet.Using the double weight amount of 97.7% potassium hydroxide as ester and heating to 380 ° 0 for at least 2 1/4 hours, only 28.4% pure di-n-propylacetonitrile, based on the starting cyan acetate, was obtained.
Et lignende forsøg, der udførtes med den samme mængde 98%'s natriumhydroxid under de samme betingelser med hensyn til temperatur og varighed, gav et udbytte på 44,4% di-n-propylacetonitril beregnet på udgangscyanacetatet.A similar experiment conducted with the same amount of 98% sodium hydroxide under the same temperature and duration conditions gave a yield of 44.4% di-n-propylacetonitrile based on the starting cyanoacetate.
Af alle de ovenfor angivne resultater ses det klart, at fremgangs måden ifølge opfindelsen umiskendeligt indebærer fordele i forhold til de i den kendte teknik foreslåede fremgangsmåder.From all the results set forth above, it is clearly seen that the method of the invention unmistakably has advantages over the methods proposed in the prior art.
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Fremgangsmåden ifølge opfindelsen har endvidere vist sig at være de tidligere omtalte kendte fremgangsmåder, som anvendes til fremstilling af di-n-propylacetonitril, overlegen.Furthermore, the process of the invention has been found to be superior to the previously mentioned known processes used for the preparation of di-n-propylacetonitrile.
Fremgangsmåden ifølge opfindelsen illustreres nærmere i de følgende eksempler.The process of the invention is further illustrated in the following examples.
Eksempel 1.Example 1.
Fremstilling af di-n-propylacetonitril. a) Di-n-propylcyaneddikesyre.Preparation of di-n-propylacetonitrile. a) Di-n-propylcyanacetic acid.
Først fremstilledes en natrium-n-propylatopløsning ud fra 7,4-2 g (0,322 mol) natrium og 180 ml vandfri n-propanol ved opvarmning under rolig tilbagesvaling indtil fuldstændig opløsning af natriumet.First, a sodium n-propylate solution was prepared from 7.4-2 g (0.322 mol) of sodium and 180 ml of anhydrous n-propanol by heating under gentle reflux until complete dissolution of the sodium.
I en 5OO ml rundkolbe, der var forsynet med en dråbetragt, en mekanisk omrører, et termometer og en kondensator, over hvilken var anbragt en calciumchlorid-fælde, kom man 16,95 g (0,141. mol) ethyl-cyanacetat og 40,69 g (0,33 mol) n-propylbromid. Denne blanding opvarmedes til 45°C, og derefter tilsattes langsomt og under omrøring den ovenfor fremstillede opløsning af natrium-n-propylat under opretholdelse af en temperatur i reaktionsmediet på 50-55°0 ved let ydre køling.Into a 500 ml round-bottom flask equipped with a dropper funnel, mechanical stirrer, thermometer and condenser over which was placed a calcium chloride trap, 16.95 g (0.141 mole) of ethyl cyanoacetate and 40.69 were added. g (0.33 mol) of n-propyl bromide. This mixture was heated to 45 ° C and then slowly and with stirring, the solution of sodium n-propylate prepared above was added while maintaining a temperature in the reaction medium of 50-55 ° 0 with slight external cooling.
Efter afsluttet tilsætning opvarmedes blandingen til tilbagesvalingstemperatur i løbet af 30 minutter, og denne temperatur opretholdtes i 3 timer. n-Propanolet blev derefter afdestilleret, og man afbrød destillationen, da temperaturen af remanensmassen nåede 115°C.After completion of the addition, the mixture was heated to reflux temperature over 30 minutes and this temperature was maintained for 3 hours. The n-propanol was then distilled off and the distillation was discontinued as the temperature of the residue reached 115 ° C.
Den på denne måde opnåede rå ester blev derefter behandlet med en opløsning af 7,5 g natriumhydroxidflager i 67,5 ml vand. Blandingen hældtes i en 250 ml rundkolbe, der var udstyret med en kondensator, og derefter opvarmedes reaktionsmediet langsomt til 60-70°C. Denne temperatur opretholdtes i 3 timer, hvorefter blandingen blev afkøletThe crude ester thus obtained was then treated with a solution of 7.5 g of sodium hydroxide flakes in 67.5 ml of water. The mixture was poured into a 250 ml round bottom flask equipped with a condenser and then the reaction medium was slowly heated to 60-70 ° C. This temperature was maintained for 3 hours, after which the mixture was cooled
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12 til ca. 50°0, og det dannede ethanol og resten af n-propanolet fjernedes under et tryk på 70 mm Hg. Den således opnåede opløsning afkøledes til 20°C og syrnedes, idet der under omrøring tilsattes 26,25 g 36%'s saltsyre. Under denne arbejdsgang holdtes reaktionsmediets temperatur under 40°C ved afkøling. Omrøringen fortsattes i 30 minutter, hvorefter blandingen henstod i 30 minutter. Det olieagtige lag af di-n-propylcyaneddikesyre blev dekanteret fra, og den vandige fase ekstraheredes med 35 ml toluen. Ekstrakten i toluen sattes derefter til den fradekanterede di-n-propylcyaneddikesyre, hvorefter opløsningen i toluen vaskedes i en skilletragt med en opløsning af 1,5 g natriumchlorid i 14 ml vand. Den toluene fase blev fradekanteret og toluenet afdestilleret under atmosfærisk tryk.12 to approx. 50 ° 0 and the ethanol formed and the remainder of the n-propanol removed under a pressure of 70 mm Hg. The solution thus obtained was cooled to 20 ° C and acidified, adding with stirring, 26.25 g of 36% hydrochloric acid. During this operation, the temperature of the reaction medium was kept below 40 ° C upon cooling. Stirring was continued for 30 minutes, after which the mixture was allowed to stand for 30 minutes. The oily layer of di-n-propylcyanacetic acid was decanted and the aqueous phase was extracted with 35 ml of toluene. The extract in toluene was then added to the decanted di-n-propylcyanacetic acid, after which the solution in toluene was washed in a separatory funnel with a solution of 1.5 g of sodium chloride in 14 ml of water. The toluene phase was decanted off and the toluene distilled off under atmospheric pressure.
Ved anvendelse af denne fremgangsmåde fik man 25 g rå di-n-propylcyaneddikesyre .Using this process, 25 g of crude di-n-propylcyanacetic acid were obtained.
b) Di-n-propylacetonitril.b) Di-n-propylacetonitrile.
I en 100 ml rundkolbe forsynet med et termometer og en kondensator kom man 25 g rå di-n-propylcyaneddikesyre opnået efter den ovenfor beskrevne fremgangsmåde, og blandingen opvarmedes på oliebad.In a 100 ml round-bottom flask equipped with a thermometer and condenser, 25 g of crude di-n-propylcyanacetic acid were obtained by the procedure described above and the mixture was heated on an oil bath.
Decarboxylering begyndte ved en temperatur på omkring 140°C. Blandingen opvarmedes først til tilbagesvalingstemperatur, d.v.s. til ca. 160°C, og derefter til 190°0 i løbet af 2 timer. Denne temperatur blev opretholdt,indtil gasafvigelsen var afsluttet, hvilket tog 2 timer. Den således dannede di-n-propylacetonitril afdestillere-des derefter langsomt, og den fraktion, der gik over mellem 165 og 175°0, opsamledes. Denne destilleredes derefter igen.Decarboxylation began at a temperature of about 140 ° C. The mixture was first heated to reflux temperature, i.e. to approx. 160 ° C, and then to 190 ° 0 over 2 hours. This temperature was maintained until the gas deviation was completed, which took 2 hours. The di-n-propylacetonitrile thus formed is then distilled off slowly and the fraction passing between 165 and 175 ° O is collected. This was then distilled again.
Ved anvendelse af denne fremgangsmåde fik man 14,7 g di-n-propylacetonitril, kp. 170°C.14.7 g of di-n-propylacetonitrile, b.p. 170 ° C.
Udbytte: 83$ beregnet på anvendt ethylcyanacetat.Yield: $ 83 on ethyl cyanacetate used.
Eksempel 2.Example 2.
Fremstilling af di-n-propylacetonitril.Preparation of di-n-propylacetonitrile.
a) Di-n-propylcyaneddikesyre.a) Di-n-propylcyanacetic acid.
Først fremstilledes en opløsning af natrium-n-propylat ud fra 50 g (2 at.g + 10%) natrium og 804 g (1000 ml,), vandfrit n-propanol ved opvarmning ti). 50-55°^ i 60 til 90 minutter.First, a solution of sodium n-propylate was prepared from 50 g (2 at.g + 10%) of sodium and 804 g (1000 ml,), anhydrous n-propanol on heating. 50-55 ° for 60 to 90 minutes.
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99,1 g (1 mol) methylcyanacetat og 270,6 g (2,2 mol) n-propylbromid hældtes i en 2 liter rundkolbe. Massen opvarmedes "under omrøring til 45-50°C, og ved denne temperatur tilsatte man konstant opløsningen af natrium-n-propylat i propanol. Denne arbejdsgang varede fra 60 til 75 minutter.99.1 g (1 mole) of methyl cyanoacetate and 270.6 g (2.2 mole) of n-propyl bromide were poured into a 2 liter round bottom flask. The mass was heated under stirring to 45-50 ° C and at this temperature the solution of sodium n-propylate in propanol was constantly added. This operation lasted from 60 to 75 minutes.
Efter at .tilsætningen var afsluttet, opvarmedes blandingen under tilbagesvaling i 3 timer.. n-Propanolet·« blev derefter bortdestilleret., indtil temperaturen var 130-125°C i remanensmassen. Den opnåede rå estqr behandledes derefter-med 500 g 10%'s vandig natriumhydroxid-opløsning og med 0,36 g cetyltrimethylammoniumbromid.After completion of the addition, the mixture was heated under reflux for 3 hours. The n-propanol was then distilled off until the temperature was 130-125 ° C in the residue. The crude ester obtained was then treated with 500 g of 10% aqueous sodium hydroxide solution and with 0.36 g of cetyltrimethylammonium bromide.
Blandingen opvarmedes under tilbagesvaling i 1 time og afkøledes derefter til ca. 50°C, hvorefter de resterende alkoholer fjernedes under formindsket tryk (50 til 100 mm Hg).The mixture was heated at reflux for 1 hour and then cooled to ca. 50 ° C, after which the remaining alcohols were removed under reduced pressure (50 to 100 mm Hg).
Den opnåede opløsning afkøledes og symedes derefter, uden at temperaturen overskred 40°C ved hjælp af 175 g 36$'s saltsyre. Blandingen holdtes i denne tilstand i 30 minutter, og derefter blev di-n-propyl-cyaneddikesyren fradekanteret. Det nedre vandige lag ekstraheredes med 250 g toluen. De to organiske fase kombineredes, vaskedes en gang med 100 g renset vand, og opløsningsmidlet fjernedes ved destillation under formindsket tryk, hvorved man fik 154,5 g rå di-n-propylcyaneddi-kesyre.The resulting solution was cooled and then sutured without the temperature exceeding 40 ° C using 175 g of 36 $ hydrochloric acid. The mixture was kept in this state for 30 minutes and then the di-n-propyl cyanoacetic acid was decanted off. The lower aqueous layer was extracted with 250 g of toluene. The two organic phases were combined, washed once with 100 g of purified water, and the solvent was removed by distillation under reduced pressure to give 154.5 g of crude di-n-propylcyanacetic acid.
b) Di-n-propylacetonitril.b) Di-n-propylacetonitrile.
Det ovenfor opnåede rå di-n-propyleyaneddikesyre overførtes til en 25Ο ml rundkolbe og blev lidt efter lidt bragt til tilbagesvalings-temperatur, hvorunder de sidste spor af toluen fjernedes ved hjælp af et Dean-Stark-system, indtil temperaturen i massen var blevet omkring 175-l80°C. Decarboxyleringen begyndte omkring 140°0, og omsætningen var praktisk taget afsluttet efter 1 times tilbagesvaling. Blandingen blev i alt holdt i 2 timer under tilbagesvaling. Massetemperaturen nåede 205-210°C i løbet af de første få minutter af tilbagesvalingsarbejdsgangen og faldt derefter igen og blev stabil omkring l85°C. Derefter destilleredes blandingen under atmosfæretryk.The crude di-n-propyleyaneacetic acid obtained above was transferred to a 25Ο ml round-bottom flask and gradually brought to reflux temperature, during which the last traces of toluene were removed by a Dean-Stark system until the temperature of the pulp was about 175-L80 ° C. The decarboxylation began at about 140 ° 0 and the reaction was practically completed after 1 hour reflux. The mixture was kept at reflux for a total of 2 hours. The mass temperature reached 205-210 ° C during the first few minutes of the reflux operation and then dropped again, becoming stable around 185 ° C. Then the mixture was distilled under atmospheric pressure.
På denne måde fik man 102,5 g di-n-propylacetonitril. Udbytte af råprodukt: 82$ beregnet på methylcyanacetat.In this way 102.5 g of di-n-propylacetonitrile were obtained. Yield of crude product: $ 82 calculated on methyl cyanoacetate.
Udbytte af rent produkt: 80$.Yield of pure product: $ 80.
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Eksempel 3«Example 3 «
Fremstilling af di-n-propylacetonitril.Preparation of di-n-propylacetonitrile.
I en 50-liters emaljeret beholder kom man 30 kg di-n-propylcyaneddike-syre. Man opvarmede -under tilbagesvaling og omrøring til 185-190°C, denne temperatur bibeholdtes som sådan i 15 minutter. Det således dannede di-n-propylacetonitril afdestilleredes, medens 69,4 kg di-n-propyl cyaneddikesyre kontinuerligt tilsattes.In a 50-liter enamelled container was added 30 kg of di-n-propylcyanacetic acid. It was heated to reflux and stirred to 185-190 ° C, this temperature was maintained as such for 15 minutes. The di-n-propylacetonitrile thus formed was distilled off while 69.4 kg of di-n-propyl cyan acetic acid was continuously added.
Tilsætningshastigheden reguleredes som funktion af af destillations-hastigheden af nitrilet, og massens temperatur holdtes på 185-190°C. Tilsætningen varede i ca. 4ir time, hvorunder der blev vundet 40,9 kg rå di-n-propylacetonitril. Destillationen fortsattes under gradvis hævning af temperaturen af massen til 206°C, og indtil arbejdsgangen var afsluttet. Arbejdsgangen varede 6 timer, hvorunder der blev vundet 16,350 kg og derefter yderligere 8,980 kg rå di-n-propylacetonitril.The addition rate was controlled as a function of the nitrile distillation rate and the mass temperature was maintained at 185-190 ° C. The addition lasted for approx. 4 hours, during which 40.9 kg of crude di-n-propylacetonitrile was obtained. The distillation was continued with gradual raising of the temperature of the pulp to 206 ° C and until the operation was completed. The workflow lasted 6 hours during which 16,350 kg and then an additional 8,980 kg of crude di-n-propylacetonitrile were gained.
Apparatet tilsluttedes reduceret tryk (ca. 100 mm Hg),og-en ny fraktion på 1,640 kg di-n-propylacetonitril opsamledes.The apparatus was connected to reduced pressure (about 100 mm Hg) and a new fraction of 1,640 kg of di-n-propylacetonitrile was collected.
Ved anvendelse af denne fremgangsmåde blev der opnået 67,87 kg di-n-propylacetonitril.Using this process 67.87 kg of di-n-propylacetonitrile was obtained.
Claims (9)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7707587 | 1977-03-15 | ||
| FR7707587A FR2383920A1 (en) | 1977-03-15 | 1977-03-15 | PROCESS FOR PREPARING AN ACETONITRILE DERIVATIVE AND DERIVATIVE OBTAINED BY THIS PROCESS |
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| DK195877A DK195877A (en) | 1978-09-16 |
| DK158038B true DK158038B (en) | 1990-03-19 |
| DK158038C DK158038C (en) | 1990-08-13 |
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| DK195877A DK158038C (en) | 1977-03-15 | 1977-05-04 | METHOD OF PREPARING DI-N-PROPYLACETONITRIL |
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| AU (1) | AU504487B2 (en) |
| BE (1) | BE854486A (en) |
| CA (1) | CA1068302A (en) |
| CH (1) | CH603563A5 (en) |
| CS (1) | CS196365B2 (en) |
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| DE (1) | DE2721265C2 (en) |
| DK (1) | DK158038C (en) |
| ES (1) | ES467125A1 (en) |
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| FR (1) | FR2383920A1 (en) |
| GB (1) | GB1522450A (en) |
| GR (1) | GR60808B (en) |
| HU (1) | HU175110B (en) |
| IE (1) | IE45345B1 (en) |
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| PT (1) | PT66542B (en) |
| SE (1) | SE441596B (en) |
| SU (1) | SU715017A3 (en) |
| YU (1) | YU40674B (en) |
| ZA (1) | ZA773779B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2470758A1 (en) | 1979-12-07 | 1981-06-12 | Sanofi Sa | METHOD FOR FIXING ALKYL GROUPS ON A CARBONIC CHAIN CARRYING A FUNCTIONAL GROUP |
| JP5036111B2 (en) * | 2001-08-20 | 2012-09-26 | 旭化成イーマテリアルズ株式会社 | Process for producing substituted cyclopentadiene |
| DE102008036495A1 (en) | 2008-08-04 | 2010-02-11 | Langhals, Heinz, Prof. Dr. | New naphthalene, perylene, benzoperylene, terrylene, quaterrylene bisimide and trisimide anions, as salts, e.g. tetrabutylammonium- or potassium-salts, useful e.g. to prepare dyes, preferably vats dye, to color cotton, paper and nylon |
| US9050302B2 (en) | 2013-03-01 | 2015-06-09 | Jazz Pharmaceuticals Ireland Limited | Method of administration of gamma hydroxybutyrate with monocarboxylate transporters |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE186739C (en) * |
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1977
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- 1977-05-04 DK DK195877A patent/DK158038C/en not_active IP Right Cessation
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- 1977-05-05 IL IL52021A patent/IL52021A/en unknown
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- 1977-05-10 HU HU77LA914A patent/HU175110B/en not_active IP Right Cessation
- 1977-05-10 CA CA278,080A patent/CA1068302A/en not_active Expired
- 1977-05-11 DE DE2721265A patent/DE2721265C2/en not_active Expired
- 1977-05-11 BE BE177457A patent/BE854486A/en not_active IP Right Cessation
- 1977-05-12 CH CH596277A patent/CH603563A5/xx not_active IP Right Cessation
- 1977-05-13 PT PT66542A patent/PT66542B/en unknown
- 1977-05-18 JP JP5816577A patent/JPS53112813A/en active Granted
- 1977-05-20 NL NLAANVRAGE7705562,A patent/NL173747C/en not_active IP Right Cessation
- 1977-05-20 CS CS773335A patent/CS196365B2/en unknown
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- 1977-05-26 DD DD7700199161A patent/DD129904A5/en not_active IP Right Cessation
- 1977-05-31 PL PL1977198559A patent/PL108183B1/en unknown
- 1977-06-03 FI FI771781A patent/FI65232C/en not_active IP Right Cessation
- 1977-06-03 GB GB23783/77A patent/GB1522450A/en not_active Expired
- 1977-06-06 SU SU772490024A patent/SU715017A3/en active
- 1977-06-08 NZ NZ184326A patent/NZ184326A/en unknown
- 1977-06-14 MX MX775804U patent/MX4779E/en unknown
- 1977-06-15 AT AT423077A patent/AT351012B/en not_active IP Right Cessation
- 1977-06-15 YU YU1490/77A patent/YU40674B/en unknown
- 1977-06-20 AU AU26263/77A patent/AU504487B2/en not_active Expired
- 1977-06-21 IE IE1270/77A patent/IE45345B1/en not_active IP Right Cessation
- 1977-06-23 ZA ZA00773779A patent/ZA773779B/en unknown
- 1977-06-27 OA OA56208A patent/OA05696A/en unknown
- 1977-07-11 IT IT25582/77A patent/IT1080764B/en active
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1978
- 1978-02-20 ES ES467125A patent/ES467125A1/en not_active Expired
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1980
- 1980-06-27 US US06/163,702 patent/USRE31260E/en not_active Expired - Lifetime
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| PBP | Patent lapsed |