SU789504A1

SU789504A1 - Method of producing aliphatic alpha-ketoacids

Info

Publication number: SU789504A1
Application number: SU792599419A
Authority: SU
Inventors: Валерия Александровна Подгорнова; Марина Савватьевна Русакова; Тамара Григорьевна Горохова; Борис Федорович Уставщиков
Original assignee: Ярославский политехнический институт
Priority date: 1979-03-03
Filing date: 1979-03-03
Publication date: 1980-12-23

Description

(54) СПОСОБ ПОЛУЧЕНИЯ АЛИФАТИЧЕСКИХ оС -КЕТОКИСЛОТ(54) METHOD FOR OBTAINING ALIPHATIC OS-CATOLL ACIDS

1one

Изобретение относитс к органическому синтезу, а именно к способу получени алифатических oi -кетокислот , которые наход т применение в фармацевтической, пищевой промышленност х и в промышленности основного органического синтеза дл получени растворителей, эмульгаторов, пластификаторов и аминокислот.The invention relates to organic synthesis, in particular, to a method for producing aliphatic oi-keto acids, which are used in the pharmaceutical, food industry and in the industry of basic organic synthesis for the production of solvents, emulsifiers, plasticizers and amino acids.

Известны способы получени СХ- -кетокислот окислением оксикислот водным раствором марганцевокислого кали l , окислением соответствующего метилкетона C2l, и окислением оксикарбамидов Р1.Known methods for producing CX-α-keto acids are the oxidation of hydroxy acids with an aqueous solution of potassium permanganate l, the oxidation of the corresponding methyl ketone C2l, and the oxidation of oxycarbamides P1.

Однако данные способы получени ОО -кетокислот представл ют в основном теоретический интерес.However, these methods for preparing OO-keto acids are mainly of theoretical interest.

Наиболее близким к предлагаемому по технической сущности и достигаемым результатам вл етс способ получени алифатических -кетокислот , например сю -кетооктановой кислоты , путем взаимодействи соответствук дей оо -нитратокислоты с водным раствором щелочи 15%-ной концентрации при ао-ЮО С с последующим выделением СХ/ -кетокислоты в виде натриевой соли, которую отдел ют фильтрованием , после чего соль подкисл ют сильной минеральной кислотой и выделенную кислоту очищают от раствора минеральной соли. Выход об -кетооктановой кислоты составл ет 77% /4 .The closest to the proposed technical essence and the achieved results is a method of producing aliphatic α-keto acids, such as cyto-octanoic acid, by reacting the corresponding nitro-o-nitrate acid with an aqueous solution of alkali of 15% concentration at ao-OO C, followed by separation of CX / α-keto acids in the form of a sodium salt, which is separated by filtration, after which the salt is acidified with a strong mineral acid and the isolated acid is purified from the mineral salt solution. The yield of α-keto-octanoic acid is 77% / 4.

5 Недостатками известного способа вл ютс невысокий выход целевого продукта, а также многостадийность процесса. При этом способ, проводимый в жестких услови х, не позвол tO ет получать низише d- -кетокислоты.5 The disadvantages of this method are the low yield of the target product, as well as the multistage process. In this case, the method carried out under stringent conditions does not allow tO to receive lower d-keto acids.

Цель изобретени - повышение выхода целевого продукта, а также упрощение процесса.The purpose of the invention is to increase the yield of the target product, as well as simplify the process.

Поставленна цель достигаетс The goal is achieved

S тем, что в способе получени алифатических сХ- -кетокислот соответствующа нитратокислота взаимодействует с 1-2 н. (4-11 вес.%) раствором щелочи при 40-70°С с последу20 к цим подкислением гидролизата до рН 3-7 сильной минеральной кислотой и вьщелением об-кетокислоты в 4-камерном электролизере с ионообменными диафрагмами при 20-25 0, силе тока 0,4-0,5 А и напр жении между платиновыми электродами 5-7 В.S by the fact that in the method of producing aliphatic cX-α-keto acids, the corresponding nitrato acid interacts with 1-2 n. (4-11 wt.%) Alkali solution at 40-70 ° С with subsequent to acidification of the hydrolyzate to pH 3-7 with strong mineral acid and absorption of keto acid in a 4-chamber electrolyzer with ion-exchange diaphragms at 20-25 0, strength current 0.4-0.5 A and voltage between platinum electrodes 5-7 V.

Исходные об-нитратокислоты получают взаимодействием сХ-олефинов с жидкой четырехокисью азота в однуBaseline nitratoacids are obtained by reacting cX-olefins with liquid nitrogen tetroxide into one

30 стадию. Выход составл ет 60-90 мол.%.30 stage. The yield is 60-90 mol%.

Увеличение выхода целевых продуктов достигают за счет изменени условий гидролиза соответствующих oiнитратокислот и принципиального изменени способа вьщелени 0 -кетокислоThe increase in the yield of the target products is achieved by changing the conditions of hydrolysis of the corresponding o-nitro acids and a fundamental change in the method of cleavage of the 0-ketoacid

Выход целевого продукта на стадии гидролиза зависит от строени bi-нитратокислоты , температуры и концентрации щелочи. Уменьшение концентрации сильной щелочи до 4-11 вес.% и Iснижение температуры до 40-70 С сО кращает долю вторичных реакций при получении oi. -кетокислот (их конденсацию ) , позвол ет синтезировать С,,Сд об -кетокислоты с выходом 70-85 мол ,%. в предлагаемом способе на стадии вьеделени при проведении электродиализа в указанных услови х сохран етс 90-98% об-кетокислоты, загруженной в электролизер.The yield of the target product at the stage of hydrolysis depends on the structure of bi-nitratoacid, temperature and alkali concentration. Reducing the concentration of strong alkali to 4-11 wt.% And decreasing the temperature to 40-70 С сО reduces the share of secondary reactions when oi is obtained. - keto acids (their condensation), allows to synthesize C ,, Cd about - keto acids with a yield of 70-85 mol%. In the proposed method, at the decomposition stage, when conducting electrodialysis under the specified conditions, 90-98% of the keto-acid loaded into the electrolyzer is stored.

Пример 1.о6 -Кетопропионова .( пировиноградна ) кислота.Example 1. O6-Ketopropion. (Pyruvic acid) acid.

В реакционную колбу загружают 200 мл (3,2 моль) жидкой четырехокиСи азота. ГазообразнЪай пропилен при 10-1 БС ввод т в реактор в течение 4 ч. Всего пропускают 0,5 моль пропилена (концентраци пропилена 94,6% пропана 0,65% бутиленов 4,7%). Избыточную четырехокись азота удал ют продувкой воздуха при 18-20 С. Получают 86 г реакционной массы, содержащей 80 масс.% об-нитратопропионовой кислоты, определ емой пол рографически (,65 В, где Ei/2 - потенциал .полуволны, фон: универсальна буферна смесь Бритона-Робинсона рН 11+1М КС1).200 ml (3.2 mol) of liquid nitrogen tetroxide are loaded into the reaction flask. Propylene gas at 10-1 BS is introduced into the reactor for 4 hours. A total of 0.5 mol of propylene is passed through (propylene concentration 94.6% propane 0.65% butylenes 4.7%). Excess nitrogen tetroxide is removed by blowing air at 18–20 ° C. 86 g of the reaction mass is obtained, containing 80% by weight of nitrate-propionic acid, determined polarographically (, 65 V, where Ei / 2 is the half-wave potential, background: universal Briton-Robinson buffer mixture pH 11 + 1M KC1).

Масло 24 г, содержащее 0,14 моль oL -нитратопропионовой кислоты, смешивают на холоде с 450 мл водного 1 н. раствора гидроокиси кали . Сме загружают в реактор и термостатируют при в течение часа. После охлаждени до комнатной температуры к продукту гидролиза, содержащему 12,4 г калиевой соли cL -кетопропионовой кислоты (выход 70% мол.%), добавл ют мочевину (дл разрушени нитрита кали или натри ) . Концентрированной сол ной кислотой подкисл ют раствор до рН 3. РН раствора определ етс рКд oi -кетокислоты. 120 г водного раствора, содержащего 3 г (Х- -кетопропионовой кислоты, заливают в предкатодную камеру четырехкамерного электролизера. В чейку с катодом, отделенную катионообменной диафрагмой, помещают 1%-ный водный раствор гидроокиси кали , в анодную и преданодные камеры, разделенные анионообменными диафрагмами, заливают 1%-ный водный раствор сол ной кислоты. Электродиализ провод т при 250с и силе тока 0,4-0,5 А. Напр жение между платиновыми электродами 5-7 В. В катодной камере концентрируетс гидроокись КсШИЯ, в24 g oil containing 0.14 mol oL -nitrate-propionic acid is mixed in the cold with 450 ml of aqueous 1N. potassium hydroxide solution. Sme load into the reactor and thermostatic at within one hour. After cooling to room temperature, urea is added to the hydrolysis product containing 12.4 g of the potassium salt of cL-ketopropionic acid (yield 70% mol.%) (To destroy potassium or sodium nitrite). The solution is acidified to pH 3 with concentrated hydrochloric acid. The pH of the solution is determined by the pKd oi-keto acid. 120 g of an aqueous solution containing 3 g (X-ketopropionic acid is poured into the pre-cathode chamber of a four-cell electrolyzer. In a cell with a cathode separated by a cation-exchange diaphragm, put 1% potassium hydroxide in anodic and pre-cell chambers separated by anion-exchange diaphragms A 1% aqueous solution of hydrochloric acid is poured in. Electrodialysis is carried out at 250 s and an amperage of 0.4-0.5 A. The voltage between platinum electrodes is 5-7 V. In the cathode chamber, xychia hydroxide is concentrated, in

анодном пространстве - минеральна кислота.the anode space is mineral acid.

Из предкатодной камеры выгружают 2,7 г oi-Кетопропионовой кислоты в виде водногораствора. На стадии вьщелени сохран етс 90% а -кетокислоты , загруженной в электролизер. В дл of- -кетокислоты. Т.пл/ 2,4-динитрофенилгидразона- oi -кетопропионовой кислоты 217,5°С (из спирта).2.7 g of oi-Ketopropionic acid in the form of an aqueous solution are discharged from the pre-cathode chamber. At the stage of allocation, 90% of α-keto acid loaded into the electrolyzer is retained. In for of-keto acids. Mp / 2,4-dinitrophenylhydrazone-oi-ketopropionic acid 217.5 ° C (from alcohol).

Q Литературные данные т. пл. 2,4-ДНФГ-пировиноградной кислоты 218°С.Q Literary data so pl. 2,4-DNPH-pyruvic acid 218 ° C.

Пример 2.oi -Кетомасл на кислота. . Аналогично примеру 1 получаютExample 2.oi-ketoml acid. . Analogously to example 1, receive

3 jyi. -нитратомасл ную кислоту пропусканием газообразного оС -бутилена в жидкую четырехокись азота. Остаток после удалени четырехокиси азота, содержащей 76% cs6 -нитратомасл ной3 jyi. -Nitra-butyric acid by passing gaseous oC -butylene to liquid nitrogen tetroxide. The residue after removal of nitrogen tetroxide, containing 76% cs6 -nitro-oil

0 кислоты (, в), промывают водой, сушат над сернокислым натрием и перегон ют в вакууме. Собирают фракцию oi, -нитратомасл ной кислоты при ЮО-ЮЗ с и давлении 3 мм рт.ст.0 acid (, c), washed with water, dried over sodium sulfate and distilled in vacuo. A fraction of oi, nitrobutyric acid is collected at SO-SW with a pressure of 3 mm Hg.

5 25 г Сб -нитратомасл ной кислоты (0,17 моль) смешивают на холоде с 430 мл 1 н. водного раствора гидроокиси натри . Смесь загружают в реактор , термостатируют при 70 С в5 to 25 g of Sat-nitrobutyric acid (0.17 mol) is mixed in the cold with 430 ml of 1N. an aqueous solution of sodium hydroxide. The mixture is loaded into the reactor, thermostatic at 70 ° C.

n течение 3 ч. Получают 16,8 г натриевой соли сх -кетобутановой кислоты (выход 80 мол.%) в виде водного раствора . После охлаждени до 25с продукт гидролиза подкисл ют конс центрированной сол ной кислотой до рН 3 в присутствии мочевины. Водный раствор оС -кетомасл ной кислоты подвергают электродиализу аналогично примеру1. Из предкатодной камеры выгружают OL -кетомасл ную кислотуn for 3 h. Obtain 16.8 g of sodium salt of Cx-ketobutanoic acid (yield 80 mol.%) in the form of an aqueous solution. After cooling to 25 ° C, the hydrolysis product is acidified with concentrated hydrochloric acid to pH 3 in the presence of urea. An aqueous solution of C-feto-butyric acid is subjected to electrodialysis as in Example 1. OL oleaginous acid is discharged from the pre-catalyst chamber.

в виде 5%-ного водного раствора. Пол рографическим анализом показано, что сохран етс 95% от загруженной в электролизер о -кетомасл ной кислоты . В дл rt. -кетомасл нойin the form of a 5% aqueous solution. Polographic analysis showed that 95% of the o-butyric acid was loaded into the electrolyzer. In for rt. - oil

5 кислоты. Т. пл. семикарбазона 0 -кетомасл ной кислоты (из ацетона) 21 (Яс.5 acid. T. pl. semicarbazone 0 -fetobutyric acid (from acetone) 21 (Yas.

Литературные данные J2j: т. пл. семикарбазона .Literary data J2j: m. Pl. semicarbazone.

Пример 3. об -Кетовалери-.Example 3. about -Cetovaleri-.

0 анова кислота.0 anovy acid.

Claims

Analogously to Example 1, oi-nitratovaleric acid is obtained by passing pentene-1 gaseous gas to liquid nitrogen tetroxide. The residue, after removal of excess nitrogen tetroxide, containing 70% of cx -nittovaleric acid, is washed with water, dried over sodium sulfate and distilled in vacuo. Collect the fraction (X- -nitratovalerianic acid at 116-118 ° C and a pressure of 3 mm Hg, which is used to produce cX ketovaleric acid. 28 g of 0 -nitratovaleric acid (0.17 mol) are mixed in the cold with 430 ml 1 an aqueous solution of potassium hydroxide.The mixture is loaded into the reactor and thermostatic at 3 hours. The hydrolysis product contains 21.6 g (yield 80 mol.%) of the potassium salt of nitrate esteric acid, determined polarographically (, 46). a solution of 0-ketovaleric acid by electrodialysis is carried out analogously to example 1, T. pl. semicarb 0-ketovaleric acid ethyl ester zone 139 ° С (from benzene) .. Literature data 2: melting point of semicarbazone ethyl ester of o-ketovaleric acid. 139-140 0. Example 4.ot-Ketohexanoic acid. 220 ml are placed in a flask (3.37 mol of liquid nitrogen tetroxide and at 5–15 ° C, 88 m of hexene-1 (0.71 mol) is added with stirring. Excess nitrogen tetroxide is removed by blowing air at 18–20 sec. 126 g of reaction mass is obtained containing 70% of Oi-nitrohexanoic acid, determined polygraphically (Е ,, 47 в After washing, the chilled to + 3-С water from the nitric acid, left acids and other water soluble foods, dried over calcined sodium sulfate technical ob nitratogeksanovuyu acid was distilled in vacuo. Collect the fraction of {j-nitratoacid at 117-118 s and a residual pressure of 3 mm Hg. Art. 17.7 g (0.1 mol of 0-nitrohexanoic acid is introduced into 125 ml of 2 and potassium hydroxide solution at. The mixture is heated to and kept at this temperature for 4.5 hours. After cooling to a hydrolysis product containing 13 ,. 4 g (yield 80 mol.%) Of potassium salt 0-ketohexanoic acid, acidified to pH 7. The resulting aqueous solution of Qi-keto hexanoic acid is loaded into the pre-cathode chamber of a 4-chamber electrolyzer. Analogously to example 1, 1% is poured into the anode chamber aqueous solution of hydrochloric acid, in the cathode space - 1% aqueous solution of hydroxide potassium, a 2% aqueous solution of hydrochloric acid with urea is added to the pre-run chamber. A voltage of 5–7 V is applied to platinum electrodes, a current of 0.4–0.5 A. 0 — Keto hexanoic acid is collected in a pre-run chamber The nitrite-ion leaving the pre-cathode chamber through the anion-exchange diaphragm in the pre-reactor chamber is destroyed in the presence of urea. The contents of the pre-chamber chamber are evaporated under vacuum, Ot-Ketohexanoic acid after drying over calcined sodium sulfate at 63, and a heat of 4 mm . Art. T. pl. o - ketohexanoic acid 7, (from heptane). Literary data so pl. ketohexanoic acid. 1.46 V dL (% ketohexanoic acid. Example 5.cxi-Ketohexanoic acid. Analogously to Example 4, nitrate-hexanoic acid is obtained. After removing excess nitrogen tetroxide, the oil is neutralized to pH 6 with aqueous 2N potassium hydroxide at 0-5c. Division an organic layer comprising nitro compounds. To a 70 ml solution containing 0.1 mol of the potassium salt of o-nitrohexanoic acid, 75 ml of a 2N solution of potassium hydroxide are poured. The resulting solution is heated to and kept at this temperature for 4.5 hours Solution containing 13.4 g (yield 80%) ka The acid salt of α-ketohexanoic acid, after acidification to pH 7, is subjected to electrodialysis in a manner similar to Example 4. Example b.Co.-Ketoheptanoic acid. 160 ml (2.58 mol) of liquid nitrogen tetroxide are placed in a flask and stirred at 0.5 s. 60 ml (0.43 mol) of heptene-1. Excess nitrogen tetroxide is removed by blowing air at 25-30 C. 80 g of a mixture containing 60% Oi-nitrotoheptanoic acid is obtained, which is determined polarographically (E. ( 0.435 c). The mixture is neutralized to pH 6 with aqueous 2N. potassium hydroxide solution at 0-5s. Separate the organic layer including the nitro compounds. To 70 ml of a solution containing 0.1 mol of the potassium salt of 0-nitroheptane acid, poured 75 ml of 2N. potassium hydroxide solution. The solution is heated to and kept at this temperature for 3.5 hours. 15.5 g (yield: 83 mol.%) Of potassium salt are obtained; - ketoheptanoic acid. Purification of the oi-ketoheptanoic acid solution was carried out analogously to example 4. So pl. (-ketoheptanoic acid (from heptane), 46 B. Literary data pj: mp. C-ketoheptanoic acid 29-30 C. Example 7.O-Keto-octanoic acid. Place 150 ml (2.43 mol) of liquid tetroxide in the flask 67 ml (0.42 mol) of octene-1 is added while stirring at 10-15 ° C. Excess nitrogen tetroxide is removed by blowing air at 18-20 ° C. 96 g of a mixture containing 60% by weight of Ot-nitro-octanoic acid is obtained determined polarographically (-0.375 in). The mixture is neutralized to a pH of 6 with an aqueous 2N solution of potassium hydroxide and the organic layer is separated, including n-nitros 75 NOT 2N of potassium hydroxide solution are poured in to 70 ml of a solution containing OD of a mole of potassium salt of α-nitratoctanoic acid. The resulting solution is heated to TO-s and vyderzhayut at this temperature for 3.5 hours. After cooling to product hydrolysis, containing 16.7 g of potassium salt of o-keto-octanoic acid (yield 85 mol,%) is acidified to pH 7. The salt solution of 0-keto-octanoic acid is loaded into the pre-cathode chamber 4 of the chamber electrolyzer. CONDITIONS of electrodialysis are similar to example 4, 13.2 g of OS-keto-octanoic acid are discharged from the pre-chamber chamber. At the release stage, 98 mol% of α-keto-octanoic acid stored in the electrolyzer is stored. Ei / 2.if46 B dl with keto-octane acid. T, p, C6-ketoooctanoic acid, so pl. 2,4-DNPH-0 {-keto-octanoic acid 135.5 p. (From alcohol) Literature data I: so pl. (U.-keto-octanoic acid, mp 2, 4-DNPH-CH-keto-octane. Acid 136.5-137.5 ° C. The total yield of keto-octanoic acid is 83 mol.%. Example b, o1-Ketopropionic acid. 32 g of the oil obtained in Example 1 and containing 0.19 mol of d -nit rotopropionic acid is mixed in the cold with 200 ml of 2N potassium hydroxide solution. The mixture is loaded into the reactor and thermostatic at 40 ° C for 2 hours. After cooling to a coagulative temperature, urea is added to the hydrolysis product containing 14.4 g (60% by weight of potassium salt of sk-ketopropionic acid). This hydrochloric acid acidifies the solution to pH 3. The solution of the oi-ketopropionic acid and solution is carried out similarly to Example 1. The process is simplified, the yield of the desired products is increased by reducing the number of operations at the oi-keto acid isolation stage. at 40-70 ° C and in the presence of 1-2N alkali, it allows to obtain lower and -carboxylic acids, for example, pyruvic or o-oil-oil. Claim of the method of producing aliphatic OL-keto acids by reacting Oi -nitratokisloty it with an aqueous alkali solution with heating, followed vtstseloniem desired product from the reaction mixture, characterized in that, in order to increase the yield and simplifying the process, use 1-2 n. alkali solution, the process is carried out at 40-7OfС with the selection of the target product by sub-. acidification of the reaction mass to pH 37, followed by electrodialysis in a four-cell electrolyzer with ion-exchange diaphragms at 2025 s, current 0.4-0.5 A and nationality between platinum electrodes 5-7 V. Sources of information taken into account during the examination 1. The patent of the USSR No. 176288, cl. C 07 C 59/32, 1964.

2. The patent of France No. 2276283, cl. C 07 C 65/20, published 1976.

3. The patent of France No. 2127265, cl. C 07 C 51/00, published 1972.

4. The patent of Germany 1618621, cl. 120 About 15, pub. 1971 (prototype).