DE1029817B - Process for the production of ª € -ketocarboxylic acids or ªÏ-oxy-ª € -ketocarboxylic acids - Google Patents

Description

Process for the preparation of b-ketocarboxylic acids or -oxy-d -ketocarboxylic acids The invention relates to a process for the preparation of d-ketocarboxylic acids or co-oxy-d-keto carboxylic acids. d-keto acids of the general formula 1, in which R is one - optionally substituted - saturated or olefinically unsaturated aliphatic Hydrocarbon radicals with at least 4 carbon atoms are valuable Intermediate products for the production of a large number of valuable compounds.

So z. B. by reducing these keto acids d-lactones of the general formula 11, which are used as fragrances, can be prepared in a simple manner: RCO (CH2) 3COOH These acids can also be converted into fatty acids of general composition III by complete reduction of the keto group: Furthermore, these keto acids can, for. B. can also be used for the production of valuable macrocyclic lactones of the general formula IV if the group R is chosen so that it contains a preferably terminal reactive group, for example a double bond or a hydroxyl or acyloxy group or a halogen atom, which directly or can react indirectly with the carboxyl group, e.g. B. according to the following equation: The starting materials used for the process according to the invention are compounds of the general formula in which R is an optionally substituted saturated or olefinically unsaturated aliphatic hydrocarbon radical having at least 4 carbon atoms and A and B can be converted into a carboxyl group by hydrolysis, for example alkoxycarbonyl, nitrile or aminocarbonyl groups, mean.

Compounds of the general formula V can be obtained in a known manner by condensation of an acid halide with a compound of the general formula VI or VII according to the following equations: Compounds of the formula V are generally not distillable, but they can be converted into the desired keto acids in crude form according to the process of the present invention, which further simplifies the process.

The preparation of these starting materials is very simple in that the cyanoethylation method and its variants can be used, ie the condensation of an ester of acetoacetic acid with acrylonitrile, acrylamide or esters of acrylic acid in the presence of alkaline catalysts. This reaction is illustrated by the following equations in which Et means ethyl and Me means methyl.

The process is based on selective cleavage of the acetyl group from a compound of the general formula V by alkaline hydrolysis or alkali-catalyzed Alcoholysis with subsequent alkaline hydrolysis, preferably at a temperature between 70 ° C and the boiling point of the reaction mixture, while maintaining the larger Acyl group and the group -GH2 CH2 A, which follows or preferably simultaneously carried out saponification of group A to one Carboxyl group and removal of the Group B by hydrolysis and decarboxylation.

It is very surprising that these reactions occur in a single Stage can be carried out.

It is also surprising that the group-C H2 C H2A is not split off to a considerable extent during the process, since it is known (cf. CK Ingold, "Structure and Mechanism in Organic Chemistryzr [1953], 5. 692) that the so-called" Michael -Addition «in an alkaline medium according to the equation is reversible.

For this reason it was to be expected that through the action from alkali not only one of the acyl groups would split off the group B, but also the group - CH2CH2A. Apparently the acetyl group is removed and group B so rapidly that the cleavage of the CH2CH2A group is practically complete is avoided and you can get the ketocarboxylic acid in good yield.

The reaction is preferably carried out with 10 to 25% sodium bicarbonate or Potassium hydroxide carried out as a hydrolyzing agent.

Isbell, Wojcik and Adkins ("Journal of the American Chemical Societyfi, Vol. 54 [1932], 5. 3678) have the question of whether it is possible to use ketocarboxylic acids general formula 1 to produce from esters of formula V, examined in detail. The processes tested by these authors are: Alcoholysis at 60 ° C in the presence of hydrochloric acid and alcoholysis at 150 to 2500 C and 100 at.

However, in these experiments, with the exception of one In the case where R was an aromatic group, that mainly the larger of the was split off both acyl groups.

It is therefore surprising that it is in contrast to Isbell's and employees described results was possible, mainly the smaller ones cleavage of the two acyl groups from a compound of the general formula V. and to obtain the desired ketocarboxylic acid in good yield.

The following examples are intended to explain the process according to the invention in more detail explain.

Example 1 a) 66.8 g (2.75 moles) of magnesium and 725 g of absolute benzene are heated to boiling after adding 15 g of carbon tetrachloride, then are 15 g of absolute ethanol were added within 10 minutes. As soon as implementation begins, Gradually add 238 g of absolute ethanol and then also at the boiling point slowly adding 594 g (2.75 mol) of 4-keto-3-ethoxycarbonyl-pentanecarboxylic acid methyl ester. The mixture is then heated to boiling for a further 1112 hours, cooled to 25 ° C. and added dropwise 506 g (2.5 mol) of decene (9) carboxylic acid chloride are obtained within half an hour admitted.

After 1/4 hour stirring at 25 ° C and some time at 35 ° C finally 1500 g of 10% sulfuric acid were added while cooling with ice water. After working up and distilling off the benzene, 989 g of crude 4-keto - 3 - acetyl -3 - ethoxycarbonyltetradecene (13) carboxylic acid methyl ester obtained, b) 395.5 g of this crude product are heated to boiling with 1000 g of methanol and within 600 g of 33% sodium hydroxide solution were added for 25 minutes. The boiling will be another 25 minutes continued and the methanol is distilled off. After cooling and acidification, that becomes Extracted mixture with benzene and the 4-Ketotetradecen- (13) -carbonsäure- (1) from Recrystallized petroleum ether. The yield is 48% of theory, based on the acid chloride used. F. = 68 to 68, So C, After the reduction the keto group can this compound according to the method of patent 831 547 be converted into the valuable fragrance pentadecanolide.

Example 2 The crude 4-keto-3-acetyl-3-ethoxycarbonyltetradecene (13) carboxylic acid methyl ester is produced according to Example 1. 197.5 g of the crude product are heated to 70.degree and within half an hour with 800 g of 12.5% sodium hydroxide solution while stirring offset. Stirring at 70 ° C is continued for another half hour, then is cooled, poured into 650 g of 20% sulfuric acid and worked up as in Example 1. Yield 50% of theory, based on - the acid chloride of 4-ketotetradecene (13) carboxylic acid (1). F. = 67 to 68 ° C.

Example 3 196 g of crude ester according to Example 1, a) are within a A quarter of an hour was added to 800 g of 12.5% sodium hydroxide solution with stirring and heating. Stirring is continued until the reaction has ended, then work-up is carried out. Yield 50% of theory, based on the acid chloride of 4-ketotetradecene (13) carboxylic acid (1) used. F. = 67 to 68 ° C.

Example 4 400 g of 25% sodium hydroxide solution are heated to 70 ° C. and within a quarter of an hour with stirring with 196 g of crude ester according to Example 1, a) offset. Stirring is continued until the reaction is complete, then is being worked up. After recrystallizing the crude keto acid from petroleum ether the ketotetradecenecarboxylic acid is based in a yield of 47% of theory on the acid chloride used, on 4 - ketotetradecene - (13) - carboxylic acid - (1) obtain.

F. = 67 to 68 ° C.

Example 5 The keto-3-ethoxycarbonyl-pentanecarboxylic acid methyl ester is condensed according to Example 1) a) with decenecarboxylic acid chloride. After completion the condensation is a solution of 5.8 g (0.25 mol) of sodium in 402 g of absolute Added ethanol and then heated to boiling for 1/2 hour. Cool to room temperature and acidified with 10% sulfuric acid. After washing it, you distill it Benzene completely and gives 2000 g of methanol. Heat to the boil and add 1200 g of 33% sodium hydroxide solution are added dropwise. After the hydrolysis is complete worked up according to example 1. The ketotetradecenecarboxylic acid is in one yield of 49% of theory, based on the acid chloride used, of 4-ketotetradecene (1 3) -carboxylic acid- (l). F. = 67 to 68 ° C.

Example 6 1426 g (6.6 mol) of 4-keto-3-ethoxyearbonyl-pentanecarboxylic acid methyl ester are with 891 g (6 mol) of hexanecarboxylic acid chloride using 160.4 g (6.6 Mol) magnesium according to Example 1, a) condensed.

After removal of the solvent, 1849 g of crude methyl ester are obtained the 4-keto-3-acetyl-3-ethoxycarbonyldecanecarboxylic acid (l) obtained. 800 g 12.5% Sodium hydroxide solution is heated to 70 ° C. and with 154 g of the crude condensation product added dropwise with stirring within a quarter of an hour. The warming will continued until the hydrolysis is complete. It is poured into 650 g of 20% sulfuric acid and works on.

The crude keto acid is distilled in vacuo and. from petroleum ether recrystallized. The yield is 46% of theory, based on the amount used Hexanecarboxylic acid chloride, of 4-ketodecanoic acid- (l). F. = 57.5 to 58.5 ° C. 363 ° / o the theory of hexanecarboxylic acid are obtained as a by-product.

Example 7 To 2000 g of 5% sodium hydroxide solution heated to 70 ° C. are added 154 g of the crude methyl ester of Ketoacetyläthoxycarboonyldecancarbonsäure prepared according to Example 6, added within a quarter of an hour. Then after adding heated by 25 cc of ethanol until the hydrolysis is complete. After working up and recrystallization, the yield is 44% of theory of 4-ketodecanecarboxylic acid- (l). M.p. = 58.5 to 59.5 ° C.

Example 8 300 g of 33% sodium hydroxide solution are heated to 70 ° C. and with 154 g of the crude methyl ester of ketoacetylethoxycarbonyldecanecarboxylic acid prepared according to Example 6 added within 20 minutes with stirring. The mixture is heated until the reaction has ended and works on. The yield is 400 / o of theory of 4-ketodecanecarboxylic acid- (l). F. = 57.5 to 58.5 ° C.

Example 9 800 g of potassium hydroxide solution are heated to 70 ° C. with stirring. 154 g of crude methyl ester of ketoacetylethoxycarbonyldecanecarboxylic acid are then added within 15 minutes with stirring. Stirring is continued until the completion of the reaction continued, which takes about 1 hour. It is poured into dilute sulfuric acid and works on. The yield is 45% of theory of 4-ketodecanecarboxylic acid- (l). F. = 58.5 to 59.5 ° C. Hexanecarboxylic acid is obtained as a by-product.

Example 10 800 g of 12.5% sodium hydroxide solution are heated to the boil and with 154 g of the crude methyl ester of ketoacetylethoxycarbonyldecanecarboxylic acid prepared according to Example 6 offset within a quarter of an hour.

After boiling for 1 hour, it is worked up. The yield is 46% of the theory of 4-ketodecanecarboxylic acid- (l). F. = 57.5 to 58.5 ° C. 23 g hexanecarboxylic acid are obtained as a by-product.

Example 11 A mixture of 300 g of 33% sodium hydroxide solution, 200 g Water and 300 g of alcohol are heated to the boil and, within 20 minutes, with 154 g of crude methyl ester of ketoacetylethoxycarbonyldecanecarboxylic acid are added.

Stirring is continued until the reaction is complete, then the alcohol is distilled off and worked up in the usual way. The yield of 4-kete decanecarboxylic acid- (1) is 48% of theory; 22.5 g hexanecarboxylic acid are recovered.

Example 12 200 g of 5% sodium hydroxide solution are heated to the boil and within a quarter of an hour with 154 g of the crude prepared according to Example 6 Added methyl ester of ketoacetylethoxycarbonyldecanecarboxylic acid. One heats up until the end of the reaction and works on. The yield at 4-ketodecanecarboxylic acid- (l) is 48% of theory. F. = 58.5 to 59.5 ° C.

Example 13 500 g of 20% sodium hydroxide solution are heated to 40 ° C. and adds 154 g of the prepared according to Example 6 within 10 minutes at this temperature crude methyl ester of ketoacetylethoxycarbonyldecanecarboxylic acid. The stirring will continued until the end of the saponification, then it is worked up in the usual way.

The yield of 4-ketodecanecarboxylic acid (l) is 430 / or theory, based on the acid chloride. F. = 58.5 to 59.5 ° C.

Example 14 594 g of methyl ester of 4-keto-3-ethoxycarbonylpentanecarboxylic acid are using 66.8 g of magnesium with 371 g of hexanecarboxylic acid chloride according to the example 1, a) condensed.

When the condensation has ended, a solution of 5.8 g of sodium is added in 402 g of absolute ethanol and heated to boiling for 1/2 hour. You get mad washes until neutral and removes the solvent. During the distillation 34% of theory are ethyl hexanecarboxylate, 39% ethyl ester of 4-keto-3-ethoxycarbonyl-pentanecarboxylic acid and 50% ethyl ester of 4-keto-3-ethoxycarbonyldecanecarboxylic acid. at When this process was carried out a second time, these amounts were 28, 43 and 53%. The last compound is at the boiling point with a mixture of 436 g of 33% Sodium hydroxide solution and 720 g of methanol are saponified. After reconditioning and cleaning the ketodecanecarboxylic acid in a yield of 8S% of theory, based on the used ethyl ester of 4-keto-3-ethoxycarbonyldecanecarboxylic acid, or 42 bis 45 ° / 0, based on the hexanecarboxylic acid chloride.

Example 15 197 g of 3-ethoxycarbonyl-4-keto-pentanecarboxylic acid nitrile are condensed according to Example 1 with 132 g of caproyl chloride using 26.2 g of magnesium. After the condensation has ended, the crude reaction product is in a stage according to Example 13 (yield 42e4%) or worked up according to Example 14 in two stages. The hydrolysis continues until no more ammonia escapes. Here receives one 41.4% Ketononancarbonsäure- (l). F. = 55 to 55.5 ° C.

Example 16 594 g of methyl ester of 4-keto-3-ethoxy carbonyl pentanecarboxylic acid are according to Example 1 with 406 g of heptanecarboxylic acid chloride and 66.8 g of magnesium condensed. After completion of the reaction, a solution of 10 g of potassium in 402 g of ethanol added, heated to boiling for 1/2 hour, cooled, and with cooling and With stirring, 2000 g of 10% sulfuric acid are added. One washes until neutral Reaction, the solvent is distilled off and the residue is fractionated.

32% of recovered heptanearboxylic acid and 32% of ethyl ester are obtained of 4-keto-3-ethoxycarbonylpentanecarboxylic acid and 56% ethyl ester of 4-keto-3-ethoxycarbonyl-undecanecarboxylic acid (439 g). This is mixed with 878 g of methanol, heated to boiling and dropwise 509 g of 33% sodium hydroxide solution were added. After the hydrolysis is complete, the Methanol is distilled off and the reaction mixture with acidified with dilute sulfuric acid After working up and recrystallization, the 4-ketoundecanecarboxylic acid (l) in a yield of 46% of theory, based on the heptanecarboxylic acid chloride used, obtain. F. = 67 to 68 ° C.

If the reaction is carried out in one step by saponification of the crude condensation product is carried out at the boiling point with 15% sodium hydroxide solution, the same is done Yield obtained.

Example 17 706.5 g (2.5 moles) of 10-bromodecanecarboxylic acid chloride become according to Example 1 with 632.5 g (2.75 mol) of ethyl ester of 4-keto-3-ethoxycarbonyl-pentanecarboxylic acid condensed in the presence of 66.8 g (2.75 mol) of magnesium.

After the end of the condensation, 1500 cc of 10% sulfuric acid become admitted; after washing, the solvent is distilled off. The weight of the crude ethyl ester of 4-keto-3-acetyl-3-ethoxycarbonyl-1bwm-tefradecanecarboxylic acid is 1227 g.

4800 g of 12.5% sodium hydroxide solution (15 mol) are heated to the boil and dropwise over 15 minutes with stirring at the boiling point with 1227 g of the crude condensation product added. After boiling for 4 hours it is cooled to room temperature and 1700 g of 35% sulfuric acid are added with cooling to. 1250 cc of benzene are added, the mixture is heated to 70 ° C. with stirring and mixed with 100 g acetic acid. The benzene layer is separated, washed with warm water and cooled to 10 ° C. A mixture of 14-oxy-4-keto-tetradecanecarboxylic acid crystallizes out and 1 0-oxydecanecarboxylic acid from. It is filtered and dried and 435 g are obtained. To the separation gives L4-oxy-4-keto-tetradecanecarboxylic acid with a melting point of 88 to 89 ° C in a yield of 45 ° 10, based on the bromodecanecarboxylic acid chloride used.

After reduction of the keto group, this compound can be cyclized be converted into the valuable fragrance pentadecanolide.

Claims (3)

PATENT CLAIMS: 1. Process for the preparation of b-ketocarboxylic acids of the general formula or # -Oxy - # - ketocarboxylic acids, characterized in that a compound of the general formula in which A and B can be converted into carboxyl groups by hydrolysis and R is an optionally substituted aliphatic saturated or olefinically unsaturated hydrocarbon radical with at least 4 carbon atoms, an alkaline hydrolysis or an alkali-catalyzed alcoholysis with subsequent alkaline hydrolysis, preferably at a temperature between 70 ° C and the boiling point of the reaction mixture, then the group A is hydrolyzed to a carboxyl group and the group B is removed by saponification and decarboxylation. 2. The method according to claim 1, characterized in that the Carries out hydrolysis with a 10 to 250/0 aqueous solution of an alkyl hydroxide. 3. The method according to claim 1 and 2, characterized in that one a starting product is used whose group R contains a reactive group, which changes into a hydroxyl group during hydrolysis. ~~~~~~~ Considered Publications: "Journal of Ainerican Chemical Society", Vol. 54 [1932], p. 3678 to 3687.