DE843405B - Process for the separation of the diastereoisomeric octahydrophenanthrene carboxylic acid esters - Google Patents

Description

Issued on the basis of the First Transitional Act of July 8, 1949

(WiGBl. P. 175)

FEDERAL REPUBLIC OF GERMANY

GERMAN PATENT OFFICE

PATENT LETTERING

CLASS 12 ο GROUP 16

P 35235 IVd 1120 D.

ISSUED JULY 7, 1952

Dr. Max Schmid, Riehen (Switzerland)

has been named as the inventor

Ciba Aktiengesellschaft, Basel (Switzerland)

Process for the preparation of acyl derivatives of amides

of acetoacetic acid

Patented in the territory of the Federal Republic of Germany on February 27 , 1949, patent application published on October 25, 1951

Patent issued May 15, 1952

The priority of registrations in Switzerland from July 30, 1946 and May 23, 1947

is used

It has been found that acyl derivatives of amides of acetoacetic acid are obtained in a smooth reaction if one uses 2 mol of an alkali metal compound of an amide of acetoacetic acid of the general formula

H H

CH ₃ - C - C - C - N - R

O Me O

in which Me stands for ι alkali metal atom and
H

- N - R denotes the radical of a diazotizable amine, 1 mol of an acylating agent act and if you then add the components of the

resulting mixture separates from one another due to their different solubilities. If necessary, the resulting metal compound becomes the general formula

Il - ο η ³ - \ Il I

) C — C — N —RR ₁ -C

Me

in which Me and - N - R have the meaning already given and the atomic grouping R ₁ - CO -

corresponds to the acylating agent, the acetoacetic acid amide derivative formed set in freedom in a manner known per se.

The new method can e.g. B. in water immiscible solvents such as benzene or Chlorobenzene. In this case, e.g. B. the amide of acetoacetic acid in this Solvents are entered; it is then converted into its alkali metal compound and thereupon

ίο with the acylating agent, primarily an acid chloride or an acid anhydride. The reaction then takes place in such a way that half the alkali compound of the amide is acylated with reformation of free acetoacetic acid amide, which is now goes into solution, while the diacyl compound is precipitated as an alkali salt. After detaching it can from the filtrate about half of the applied amide can be recovered, while the residue is processed to the recovery of the new diacyl acetic acid amide. This happens e.g. B. in the Way that the crude product is dissolved in water and that from the solution by adding acid the new diacyl compound is set free.

If you work in an aqueous medium, a similar reaction takes place, with the difference that after acylation, half of the unchanged starting material was deposited from the reaction mixture while the alkali salt of the diacyl compound is in the aqueous solution.

It is filtered and the new diacyl compound is recovered from the solution by acidification. At work in an aqueous medium one can in many cases to the reaction mixture, which is formed in addition to the alkali metal salt Diacyl compound still contains proportions of the acetoacetic acid amide used as the starting material, recently give a corresponding amount of alkali hydroxide and acylating agent and so without Prior separation of the starting material or end product take the reaction one step further.

The new method is capable of very general application. So it can be done with the amides, which are available from acetoacetic ester and diazotizable primary mono- or diamines. Such diazotizable Bases are usually cyclic in nature and can be aromatic or heterocyclic Belong to series. Such amines include i-aminobenzene, i-amino-2-methylbenzene, i-amino-2- or -3- or -4-chlorobenzene, i-amino-2-methoxybenzene, i-amino-2-ethoxybenzene, i-amino-4-methoxy- or ethoxybenzene, i-amino-2,5-dimethoxy or -diethoxybenzene, 1-amino-2, 4-dimethoxy-5-chlorobenzene, i-amino-3-methylbenzene, i-amino-2-methoxy- or ethoxy-5-methylbenzene, 4, 4'-diaminodiphenyl, 4, 4'-diamino-3, 3'-dimethyldiphenyl, dehydrothiotoluidine, 2-aminothiazole, 2-aminobenzothiazole, 2-amine 0-6-methoxybenzothiazole.

As far as the acylating agents are concerned, those are expediently used which have acyl radicals even contain more than 2 carbon atoms, introduce e.g. B. chlorides of higher fatty acids, such as. B. Stearic acid chloride or chlorides of aromatic or araliphatic carboxylic acids, such as benzene-i-carboxylic acid, 2- or 3- or 4-chlorobenzene-i-carboxylic acid, 2- or 3- or 4-methoxy- or ethoxybenzenecarboxylic acid, 3- or 4-nitrobenzene-i-carboxylic acid, a-methylbenzene-i-carboxylic acid, cinnamic acid, naphthalene-i- or -2-carboxylic acid, diphenyl-4,4'-dicarboxylic acid, phthalic acids, especially terephthalic acid, Phenylacetic acid, phenoxyacetic acid.

The new process also has the advantage of great simplicity and very good yields to products that are themselves valuable intermediates in the dye industry.

The new method is surprising because it could not have been foreseen that among the proposed Reaction conditions the monoacylation at the carbon atom with practically no formation of significant amounts of by-products would run out.

Since the acylacetoacetyl compounds obtained by the present process can be converted into the corresponding acylacetyl compounds under the action of saponifying agents such as hydrochloric acid or ammonia, with the cleavage of the group CH ₃ —CO —— (cf. also French patent specification 960 788), especially if the acyl radical has a larger number of carbon atoms, the present process enables such compounds to be prepared in a simple manner.

The following examples explain the present invention without, however, reducing its scope limit. The parts mean parts by weight, unless otherwise stated, the percentages are percentages by weight. The temperatures are given in degrees Celsius.

example 1

211.5 parts of acetoacetic-o-chloroanilide (1 mol) are dissolved in 800 parts of water and 105 parts ^{by volume of a sodium hydroxide solution of 36 0} Be (1 mol + 5%) at about 40 to 50 ⁰ and the optionally filtered solution by external cooling to about ο cooled to 5 ° and slowly added 73.5 parts of benzoyl chloride ( ¹ Z ₂ mol + 5%) with vigorous stirring.

The benzoyl chloride smell disappeared in about 6 hours with formation of the sodium compound of benzoylacetoacetic acid-o-chloranilide and regression of the acetoacetic acid-o-chloranilide, which precipitates.

The suction filter is used and the product is washed with cold water. The filtrate is precipitated with hydrochloric acid 70 parts by volume of ₀ sodium 3o ° /, the Benzoylacetessigsäure-o-chloroanilide fails.

Example 2. " ⁵

211.5 parts of acetoacetic acid-o-chloranilide are in in a round bottom flask with stirrer, thermometer, filler neck and descending condenser in an oil bath 700 parts of dry chlorobenzene dissolved by heating and for complete drying of the Chlorobenzene distilled off about 100 parts. Then it is allowed to cool to about 100 ° and a solution is added, which were obtained by dissolving 23 parts of sodium in 400 parts by volume of absolute alcohol »25 is, slow too. By heating while stirring

the reaction mass is freed from alcohol as completely as possible. This is the case when the internal temperature the boiling point of chlorobenzene, d. H. 130 ". The result is a thick, white one Suspension of the sodium compound of acetoacetylo-chloranilide. If necessary, the reaction mixture is a little by adding chlorobenzene dilute. It is then cooled to about 10 ° and a mixture of 71 parts of benzoyl chloride and

ίο Slowly add about 140 parts of o-chlorobenzene. The mixture is stirred with cooling and later at room temperature for about 24 hours. The result is a light yellow Precipitation, consisting of the sodium compound of benzoylacetoacetyl-o-chloranilide. One sucks away. The filtrate, which contains half of the anilide in the solution, can be used for the next batch will. The filter residue is dissolved in water and, for the purpose of freeing chlorobenzene, a steam distillation subjected; The benzoylacetoacetyl-o-chloroanilide can then be extracted from the solution by acidification be won.

Example 3

211.5 parts of acetoacetic acid-o-chloroanilide are dissolved in

^A 5 500 parts of water and 140 parts of 3O ° / ₀ sodium hydroxide solution. A solution of 51 parts of terephthaloyl chloride in 70 parts of acetone is poured into the clear solution with thorough stirring and cooling with ice water to 10 to 15 ^{° in the course of ro minutes.} Is stirred for 4 more hours, then poured another 70 parts 3o ° / ₀ sodium hydroxide solution and a solution of 26 parts of terephthaloyl chloride in 35 parts of acetone are added and stirred overnight at room temperature. It is filtered, the residue is washed with water and purified by dissolving it in dilute sodium hydroxide solution and precipitating it with hydrochloric acid. This gives 53 parts of regenerated acetoacetic-o-chloroanilide mp. 104 ^0th The clear caustic solution is poured into a mixture of 135 parts 3o ° / ₀ hydrochloric acid and 200 parts of ice, stirred for a short time and filtered the granular precipitate. It is washed out with water and dried at 70 ^° . 157 parts of terephthaloyl-bis- (acetic acid-o-chloroanilide) are obtained.

A similar procedure is followed with the amides and the acylating agents, which result from the lists the introduction.

Example 4

2ii, 5 parts of acetoacetic acid-o-chloranilide are dissolved with 105 parts by volume of sodium hydroxide solution of 36 "Be (1 mol + 5 ° / ₀ ) in 1000 parts of water at 40 °, the solution is filtered off from impurities and cooled to ο to 5 °. Under 88 parts of p-chlorobenzoyl chloride are allowed to flow in over 30 minutes, stirred for 2 to 3 hours at ⁵⁰ , then 52 parts by volume of sodium hydroxide solution are added and 44 parts of p-chlorobenzoyl chloride are again allowed to flow in over 30 minutes and the mixture is stirred for 2 hours one with half of the previously used amounts of alkali and chloride until a total of 176 parts of p-chlorobenzoyl chloride have been consumed.Then the mixture is stirred for a further 12 hours while cooling to ⁵⁰ and then the solution is filtered off from small amounts of insoluble residues 150 parts by volume of concentrated hydrochloric acid are added, the condensation product separating out as a white precipitate which solidifies in a crystalline manner after a short time temperature, filtered and washed with water. After drying in vacuo, the condensation product is obtained in a yield of 290 to 300 parts as a white crystalline powder.

If in the above example the p-chlorobenzoyl chloride is replaced by 209.5 parts of 2, 5-dichlorobenzoyl chloride, about 300 parts of 2, 5-dichlorobenzoylacetoacetic acid-o-chloroanilide are obtained in this way.

Example 5

211.5 parts of acetoacetic acid-o-chloroanilide are dissolved with 105 parts by volume of sodium hydroxide solution of 36 ⁰ Be in 1000 parts of water and the solution is cooled to nitrided ο ° to 5 °. Half of a solution of 185.5 parts of p-nitrobenzoyl chloride in 200 parts of dioxane is allowed to flow in from a graduated dropping funnel, with thorough stirring. The mixture is stirred for 3 hours at ⁰ to 50, then 55 parts by volume of sodium hydroxide solution are added and half of the remaining chloride solution is allowed to flow in again. This operation is repeated about three times, each time with half the amounts of lye and chloride used previously. Then the mixture is stirred for 12 hours at 5 ^0, then filtered to remove small amounts of insoluble residues, and precipitated from the filtrate, the condensation product by adding 150 parts by volume of concentrated hydrochloric acid. The mixture is stirred at room temperature for 1 hour, then the precipitate is filtered off and washed with water. After drying, 270 to 280 parts of p-nitrobenzoylacetoacetic acid-o-chloroanilide are obtained as a yellow-brown powder.

If in the above example the p-nitrobenzoyl chloride is replaced by the same amount of m-nitrobenzoyl chloride, m-nitrobenzoylacetoacetic acid-o-chloroanilide is thus obtained in good yield.

Example 6

237 parts of acetoacetic acid (2,5-dimethoxy) anilide are obtained as in Example 4 with p-chlorobenzoyl chloride condensed. The p-chlorobenzoyl derivative is obtained in good yield as a white crystalline powder.

Example 7

211.5 parts of acetoacetic acid-o-chloroanilide are condensed as in Example 5 with 166.5 parts of cinnamic acid chloride dissolved in 200 parts of dioxane. This gives the condensation product in good yield ^l as a yellow crystalline powder. Acetone can also be used as a solvent for the acid chloride instead of dioxane.

Example 8

211.5 parts of acetoacetic acid-o-chloranilide are dissolved in 1000 parts by volume of dry chlorobenzene. Simultaneously one prepares a solution of 36 parts of sodium metal in 800 parts of absolute alcohol and one of 215.5 parts of 3-nitro-4-methoxyben-

Claims (1)

zoyl chloride in 300 parts of chlorobenzene. Then half of the sodium alcoholate solution is allowed to flow in with the aid of a turbine with thorough stirring, then cooled to 0 ° to 5 ° and allowed to flow in half of the chloride solution in about 30 minutes. The mixture is stirred for 2 to 3 hours until the sodium salt of the condensation product has separated out as a yellow crystalline salt. Then half of the remaining alcoholate solution is allowed to flow in again and then half of the remaining chloride solution is allowed to flow in within 30 minutes. The procedure is continued in this way until practically all of the solutions have been consumed, then the mixture is stirred for a further 12 hours at ⁵⁰ and the precipitate which has separated out is filtered off with suction. Dissolve the salt mixture in 1000 parts of water, removes the adhering chlorobenzene in vacuo at 30 to 40 ° with steam, filtered the remaining chlorobenzene Solution and the condensation product falls more concentrated by adding 150 parts by volume so hydrochloric acid. The mixture is stirred for 1 hour, filtered and washed with water. After drying in vacuo, 300 parts of 3-nitro-4-methoxybenzoylacetacetic acid-o-chloroanilide are obtained in this way as a yellow-brown crystalline powder. If you replace the acetoacetic acid chloroanilide in the above example by adding the appropriate amount of acetoacetic anilide, this is obtained in good yield 3-nitro-4-methoxybenzoylacetoacetic anilide. Example 9 109 parts of acetoacet-o-chloroanilide (product with 97.3 ° / o content of pure substance) / ₀ dissolved in 400 parts water and 50 parts by volume of sodium hydroxide solution of 30 ° at 45 to 50 ^0th When it cools down to 0 °, everything remains in solution. Within _^3/4 to 1 hour is added at -5 to O ° 25.5 parts of finely ground terephthaloyl chloride with thorough stirring. Yellow precipitation occurs immediately, which becomes thicker and thicker over time. ^{The mixture is stirred for a further 24 hours at -5 to 0} °, then the temperature is allowed to rise to about 20 °, suction filtered and washed with distilled water. The residue contains the regenerated aceto-aceto-chloranilide. The yellow solution is precipitated with cold about 50 parts by 3o ⁰ / cent hydrochloric acid to Congo red, filtered off with suction, washed until neutral to Congo with distilled water and dried at 90 to 95 ° in vacuo on a water bath. About 64 parts of terephthaloyl - bis - (acetacetic acid - ο - chloroanilide) are obtained as a beige powder. Example 10 136 parts of acetoacetic acid-2,4-dimethoxy-5-chloroanilide are stirred in 800 parts of water and 50 parts by volume of 30% sodium hydroxide solution, then without to be completely dissolved, cooled to 0 ° and treated with terephthaloyl chloride as in the previous example. The condensation of takes place in the same way Acetoacetic acid-2, S-dimethoxy ^ -chloranilide and acetoacetic acid ^ -chlor-o-methoxy ^ -methylanilide. The corresponding terephthaloyl-bis- (acetic acid anilides) with the specified substituents are obtained in this way in the anilide residue. The notation chosen here, e.g. B. H H v> Xx λ - "--— v ~, - ~~ V- * ■ V ^ - -""- i ^ i Jv O Me O CH, - R ₁ -C- I.
"C — C — N —R Me O is of course not intended to indicate that the 80 substances in question are in precisely this form must and not in another tautomeric form, CH ₃ -C = CCNR Process for the preparation of acyl derivatives of acetoacetic acid amides, thereby marked- 110 draws that on 2 moles of a compound of the general formula H
CH ₃ -CO-C -CO-NH-R, " ⁵ Me in which Me stands for 1 alkali metal atom, and H iao —-N - R is the residue of a diazotizable amine means, 1 mole of an acylating agent is allowed to act and that the constituents of the resulting mixture due to their 145 different solubilities separates. 3Me C- R ₁ -C / be able. Il
0 H or. I. PATENT APPLICATION OMe 0 NO 0 CH ₃ -Cn Il C - CH ₃ -C _x Il ^ c- O R ₁ -C ⁷ H or OMe NO Q O appear JCH: 1 5213 6.52