SE193042C1

SE193042C1 -

Info

Publication number: SE193042C1
Authority: SE
Publication date: 1964-01-01

Description

Uppfinnare: RN Goel, R Riiegg och U Schwieter Prior itet begiird frdn den 15 juni 1959 (Schweiz) Foreliggande uppfinning avser ett forfarande *for framstallning av en substituerad ldnon. Det utmarkande for ferfarandet är att man kopplar 3,4,5-trimetoxitoluen med ett diazoniumsalt av p-nitroanilin, redueerar den salunda erhallna azoforeningen till en amin och o3dderar denna. Inventors: RN Goel, R Riiegg and U Schwieter Priority Started June 15, 1959 (Switzerland) The present invention relates to a process for the preparation of a substituted ion. The distinguishing feature of the process is that coupling 3,4,5-trimethoxytoluene with a diazonium salt of p-nitroaniline, reducing the resulting azo compound to an amine and reducing it.

Den anvanda utgangsfOreningen 3,4,5-trimetoxitoluen kan framstdllas exempelvis pa foljande satt: Man loser 400 g trimetylgallussyra-metylester i 1500 ml metanol, varefter man skakar losningen 15 minuter med 100 g Raney-nickel, sâ att fororeningarna avldgsnas. Sedan man avskilt Raneynickeln och tillsatt 200 g kopparkromit, hydrerar man losningen vid 250-270° C under ett vdtgastryck av 150 at. Den erhallna metanollosningen forsattes med palladiumkol och en droppe perklorsyra, varefter man fortsatter hydreringen, tills vdtgasabsorptionen avstannar. Man avldgsnar hisningsmedlet under fOrminskat tryck och renar Aterstoden genom destillation (kokpunkt 68° C/ 0,03 mm). Man erhaller 3,4,5-triinetoxitoluen i form av en svagt, gulfargad olj a. The starting compound 3,4,5-trimethoxytoluene used can be prepared, for example, as follows: Dissolve 400 g of trimethylgallic acid methyl ester in 1500 ml of methanol, then shake the solution for 15 minutes with 100 g of Raney nickel to remove the impurities. After separating the Raney nickel and adding 200 g of copper chromite, the solution is hydrogenated at 250-270 ° C under a hydrogen gas pressure of 150 atm. The resulting methanol solution was continued with palladium carbon and a drop of perchloric acid, after which the hydrogenation was continued until the hydrogen absorption stopped. The lifting agent is removed under reduced pressure and the residue is purified by distillation (boiling point 68 ° C / 0.03 mm). 3,4,5-Triamethoxytoluene is obtained in the form of a pale yellow oil a.

Enligt en sdrskilt lOmplig utforingsform av uppfinningen kopplar man 3,4,5-trimetoxitoluenen med ett diazoniumsalt av p-nitroanilin i narvaro av ett losningsmedek exempelvis vattenhaltig alkohol. According to a particularly suitable embodiment of the invention, the 3,4,5-trimethoxytoluene is coupled with a diazonium salt of p-nitroaniline in the presence of a solvent, for example aqueous alcohol.

Den erhallna azoforeningen hydreras ldmpligen i narvaro av ett inert losningsmedel, skom en ldgre alkohol, exempelvis metanol eller etanol, eller i narvaro av attikester, med anvandning av en palladiumkatalysator. Vid anvandning av ett diazoniumsalt av p-nitroanilin sdsom kopplingskomponent kan man Mt skilja den bildade 2-mety1-4,5,6-trimetoxianffinen Iran den sasom biprodukt erhallna, i eter olosliga p-fenyldiaminen. The resulting azo compound is typically hydrogenated in the presence of an inert solvent, such as a lower alcohol, for example methanol or ethanol, or in the presence of attic esters, using a palladium catalyst. By using a diazonium salt of p-nitroaniline as a coupling component, it is possible to separate the 2-methyl-4,5,6-trimethoxyphenane Iran formed as the by-product obtained in ether-soluble p-phenyldiamine.

Den erkallua substituerade anilinen oxideras i ett sista reaktionssteg, ldmpligen vid en temperatur mellan — 20 och 40° C. Enligt en sarskilt ldmplig utforingsform loser man anilinen i form av ett syraadditionssalt i vatten, varefter man Over den vattenhaltiga losningen skiktar ett oblandbart losningsmedel, i vilket reaktionsprodukten i motsats till additionssaltet är rOslig. Sasom losningsmedel lampa sig exempelvis benzen, toluen, petroleumeter, metylenklorid, kloroform och foretradesvis eter. Det anvanda oxidationsmedlet, ldmpligen j drn( I I Dklorid, j 5111(111) sulf at eller foretrddesvis kaliumbikromat, sattes darefter under omr8ring till den av tvä laser bestdende blandningen. Under reaktionen upptages den pa detta satt bildade 3,4-dimetoxitolukinonen kontinuerligt av det overliggande organiska skiktet. The recalculated substituted aniline is oxidized in a final reaction step, typically at a temperature between - 20 and 40 ° C. According to a particularly exemplary embodiment, the aniline is dissolved in the form of an acid addition salt in water, which reaction product as opposed to the addition salt is rosy. Examples of solvents are benzene, toluene, petroleum ether, methylene chloride, chloroform and preferably ether. The oxidizing agent used, typically iron (II chloride, j 5111 (111) sulphate or preferably potassium bichromate) was then added with stirring to the two-laser mixture. overlying organic layer.

Ovan angivna steg av forfarandet kunna sammanstallas till foljande reaktionsschema: 1-13C0— H3C0-1. 1 OCH3 —CI-13 H3C0— j\ OCH3 _ -y NO /_2 /— /—CH3 II I H CO 2— — NH, III Den enligt uppfinningen framstallbara 3,4- dimetoxitolukinonen utgor en viktig mellanprodukt vid syntes av intressanta foreningar. Den anvandes exempelvis sasom utgangsforening vid framstallning av ubikinoner. The above steps of the procedure can be assembled into the following reaction scheme: 1-13CO— H3CO-1. 1 OCH 3 -CI-13 H 3 CO- j \ OCH 3 _ -y NO / _2 / - / —CH3 II I H CO 2— - NH, III The 3,4-dimethoxytolukinone which can be produced according to the invention is an important intermediate in the synthesis of interesting compounds. It is used, for example, as a starting compound in the production of ubiquinones.

Exempel. Man suspenderar 28 g p-nitroanilin i 300 ml vatten och tillsatter 60 ml koncentrerad saltsyra. Ddrefter upphettar man blandningen, sa att en klar liisning bildas, och filtrerar denna. Sedan man avkylt filtratet till 0° C i ett isbad, tillsatter man under stadigvarande omskakning en lOsning av 15 g natriumnitrit i 100 ml vatten, varvid man tillser, att temperaturen icke vid nagot tillfälle overstiger 0° C. Den erhallna diazoniumkloridlOsningen renas darefter genom filtrering. Example. 28 g of p-nitroaniline are suspended in 300 ml of water and 60 ml of concentrated hydrochloric acid are added. The mixture is then heated, so that a clear solution is formed, and filtered. After cooling the filtrate to 0 ° C in an ice bath, a constant solution of 15 g of sodium nitrite in 100 ml of water is added with constant shaking, ensuring that the temperature does not at any time exceed 0 ° C. The resulting diazonium chloride solution is then purified by filtration. .

En losning av 36 g 3,4,5-trimetoxitoluen i 200 ml alkohol i en trehalskolv, som har en volym av 1 liter och är forsedd med omrorare, avkyles till 0° C. Den enligt foregaende stycke erhallna diazoniumsaltlOsningen tillsattes under omroring mom loppet av 10-15 minuter, varvid man hailer temperaturen mellan 0 och 5° C. Man fortsatter omroringen 5-6 timmar vid denna temperatur, varefter man laLer reaktionsblandningen langsamt antaga rumstemperatur. Den erhallna roda ningen avfiltreras och omkristalliseras ur utspadd alkohol. Man erhaller pa detta satt 2-mety1-4,5,6- trimetoxi-4`-nitroazobenzen med smaltpunkten 91-93° C. A solution of 36 g of 3,4,5-trimethoxytoluene in 200 ml of alcohol in a three-liter flask, which has a volume of 1 liter and is equipped with a stirrer, is cooled to 0 ° C. The diazonium salt solution obtained according to the preceding paragraph was added with stirring over time. of 10-15 minutes, raising the temperature between 0 and 5 ° C. Stirring is continued for 5-6 hours at this temperature, after which the reaction mixture is allowed to slowly assume room temperature. The reddening obtained is filtered off and recrystallized from diluted alcohol. There is thus obtained 2-methyl-4,5,6-trimethoxy-4`-nitroazobenzene, m.p. 91-93 ° C.

Man loser 2 g 2-mety1-4,5,6-trimetwd-4'-nitroazobenzen i 50 ml metanol och tillsatter 1 g palladiumkol. Man hydrerar denna blandning, tills vatgas joke langre upptages. Sammanlagt upptagas 5 mol vate. Pet genom filtrering erhallna klara, gula filtratet indunstas omedelbart till torrhet under forminskat tryck. Man behandlar aterstoden med absolut eter, varvid 2-mety1- 4,5,6-trimetoxianilin gar i losning, medan p-fenylendiaminen till storsta delen erhalles i form av en aterstod. Efter indunstning av eterlosningen erhailer man 2-mety1-4,5,6-trimetoxi-anilin sasom en brun olja, som är mycket obestandig gentemot luftsyre och andra oxidationsmedel. Dissolve 2 g of 2-methyl- 4,5,5,6-trimethyl-4'-nitroazobenzene in 50 ml of methanol and add 1 g of palladium carbon. This mixture is hydrogenated until the water gas joke is taken up longer. A total of 5 moles of cotton is taken up. The clear yellow filtrate obtained by filtration is evaporated immediately to dryness under reduced pressure. The residue is treated with absolute ether, 2-methyl-4,5,6-trimethoxyaniline being dissolved, while the p-phenylenediamine is largely obtained in the form of a residue. After evaporation of the ether solution, 2-methyl-4,5,5-trimethoxy-aniline is obtained as a brown oil which is very resistant to atmospheric oxygen and other oxidizing agents.

Man loser 1,2 g 2-mety1-4,5,6-trimetoxi-anilin i 30 ml 3-n svavelsyra och satter den erhallna lOsningen till en med omrorare forsedd trehalskolv. Sedan skiktar man 100 ml eter Over denna lOsning. tillsatter under omroring vid rumstemperatur Mom loppet av 10 minuter en losning av 1 g kaliumbikromat i 25 ml vatten, fortsatter omriiringen 50 minuter och extraherar reaktions blandningen med eter. Den efter torkning av eterlosningen Over natriumsulfat och efter avdestillering av losningsmedlet erhallna 3,4-dimetoxi-tolukinonen bar efter omkristallisering smaltpunkten 58-59° C. Absorptionsmaximum = 805 vid 260 my (i petroleumeter). Dissolve 1.2 g of 2-methyl- 4,5,5,6-trimethoxy-aniline in 30 ml of 3-n sulfuric acid and add the resulting solution to a stirred three-necked flask. Then 100 ml of ether are layered over this solution. while stirring at room temperature for 10 minutes, add a solution of 1 g of potassium bichromate in 25 ml of water, continue the stirring for 50 minutes and extract the reaction mixture with ether. The 3,4-dimethoxy-tolukinone obtained after drying the ether solution over sodium sulphate and after distilling off the solvent had a melting point of 58-59 ° C after recrystallization. Absorption maximum = 805 at 260 ml (in petroleum ether).

Claims

Patent claim:

A process for the preparation of a substituted quinone, which can be used as an intermediate, for example for the synthesis of ubiquinones, characterized in that coupling 3,4,5-trimethoxytoluene with a diazonium salt of p-nitroaniline reduces the resulting azo compound of the formula N = N - (- NO, CI-12 H, CO - \\ // AND, ph per se salt of an amino compound of the formula NI-12 1-12C0 —— CH 3 III H3C 0— \ OCII2 later on per se edge added to 3,4-dimethoxytolukinone of the formula 0 H, C0 1-1, C0 - \) IV 0 II - —3

2. Process according to claim 1, characterized in that a diazonium salt, in particular the diazonium chloride, of p-nitroaniline is used as coupling component.

3. A process according to claim 2, characterized in that the reduction is carried out in the presence of a solvent, such as methanol, ethanol or attic ester, using a palladium catalyst and purifying the reaction product from by-products by treatment with ether.

4. A method according to claim 1, characterized in that the coding is carried out with potassium bichromate at a temperature between -20 and + 40 ° C in a two-phase mixture. Request Publications: U.S. Patent Nos. 2 351 71

5.