DE2751133A1 - PROCESS FOR CYCLIZING GAMMA CHLOROCARBON ACID ESTERS - Google Patents

Description

GERMAN GOLD AND SILVER SCHEIDEANSTALT FORMERLY ROESSLER 6OOO Prankfurt (Main), Weissfrauenstrasse 9

Process for the cyclization of Tf-chlorocarboxylic acid esters

The present invention relates to an improved process for the preparation of cyclopropanecarboxylic acids and the corresponding esters by cyclization of ^ chlorocarboxylic acid esters in Presence of an anhydrous alcoholate.

Cyclopropanecarboxylic acids and their esters are valuable intermediates for the production of agrochemical, in particular herbicidal, and pharmaceutical chemicals.

It is known to use ethyl 4-chlorobutyrate with potassium hydroxide solution To condense pumice stone. This gives a moderate yield of ethyl cyclopropanecarboxylate in addition to the free acid and -Λ-butyrolactone (Rambad, Bl. / 5 /, 5 (1938), pp. 1552, 1564).

It is also known to cyclize ^ -Chlorcarbonsäureester using anhydrous sodium alcoholates. For example, ^ -chlorobutter ethyl ester with t-sodium amylate in t-amyl alcohol is refluxed for four hours. Ethyl cyclopropanecarboxylate is obtained in a yield of k $ #. If sodium dimethylbenzylate is used as the condensing agent, the yield is 47 "fa of the theory (Bull. Soc.Chimie (France) 1960, 306 ff).

It is further known Chlorcapronsäureester ^ ^m * · * sodium amide and to condense in ether while k to 5 Tagsn 2-Methylcyclopropancarbonsäureester in a yield of 85.1 Ji theory to

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obtain. A similar experiment with Qf-methyl-x ^ -chlorobutyric acid ester yields I-methylcyclopropanecarboxylic acid ester in only ^ 7 »6 #ig < Yield (Am. Soc. 81, 1660-66).

The yields that can be achieved by the previously known processes are unsatisfactory if the condensation with alkali metal alcoholates is used performs. The operation with sodium amide is dangerous and extremely tedious, so that the transmission this procedure in the technology forbids.

According to the prior art, there is no economic one Process for the preparation of cyclopropanecarboxylic acids or their esters.

It has now been found that ^ f-Chlorcarbonsäureester <i _he general formula I

DDD

^R 4 ^R 2? I

Cl-C-C-C- COOR (i)

III

XJ Ό IJ

R ₅ R ₃ H

in which R, R, R, R ", R. and R" are identical or different and represent a straight or branched alkyl radical having 1 to k carbon atoms or, with the exception of R, can also represent a hydrogen atom, with the aid of a basic one Condensing agent and optionally subsequent saponification of the ester in yields of 90 % and more to give optionally substituted cyclopropanecarboxylic acids and their esters of the general formula II

3 /

C C - COOR (II)

^R 1

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in which the symbols R to R- have the meaning given above, and R can also stand for a hydrogen atom, cyclize can, if an anhydrous alkali metal alcoholate is used as the condensing agent, the cyclization in an inert organic Carries out solvent and continuously distilled off the alcohol formed in the reaction.

It is expedient to use an alcoholate of an aliphatic one Alcohol with 1 to 5 carbon atoms, especially a sodium or Potassium alcoholate. Examples of such alcoholates are sodium methylate, Potassium methylate, sodium ethylate, potassium ethylate, potassium isopropylate, Sodium and potassium t-butylate and sodium t-amylate. Sodium methylate is the preferred alcoholate.

Inert solvents are mainly aliphatic and cycloaliphatic and aromatic hydrocarbons, for example Benzene and Xylene, embossed. The preferred solvent is Toluene. It can also be chlorobenzene, more highly alkylated benzenes, anisole, cyclohexane, alkylated cyclohexanes, naphthalene, alkylated Naphthalenes and aliphatic hydrocarbons, in particular those with boiling points between 80 and 200 C are used will.

When carrying out the process according to the invention, ^ -halocarboxylic acid esters and alkali metal alcoholate are generally used in stoichiometric amounts. However, it is advantageous to use the alcoholate in an excess of, for example, 10 to 25 liters . This excess can be fully taken into account when saponifying the ester with alcoholates.

The process is advantageously carried out in such a way that the alkali metal alcoholate is mixed with the inert solvent, the mixture heated to boiling with stirring and then slowly

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the Tf-chlorocarboxylic acid ester is added dropwise. To the same extent is expediently via a column with a dephlegmator - the alcohol formed is distilled off, usually as an azeotrope.

The reaction temperature depends on the boiling point of that liberated during the cyclization, from the one used in each case Alcoholate derived alcohol or the corresponding azeotrope with the solvent used.

The salt formed during the reaction is either filtered off after the reaction or washed out with water. The ester is then isolated by fractional distillation. If the acid is to be obtained, the ester is saponified in a manner known per se Appropriately immediately after the condensation in the solvent. You can proceed in such a way that the dem Ester corresponding amount of alkali metal hydroxide, for example sodium or potassium hydroxide, dissolves in alcohol, preferably CH "OH or C-K OH and this solution is added dropwise to the still hot reaction mixture. The mixture is then refluxed for 1 to 2 hours, cooled and acidifies with mineral acid. The cyclopropanecarboxylic acid is now dissolved in the inert solvent and can therefrom according to the usual Methods are obtained. Purification is expediently done by rectification.

Those required as starting materials for the process according to the invention ^ -Chlorcarbonsäureester can according to known Process can be produced from the corresponding lactones (Ann. 596, 163-164).

The process according to the invention can easily be carried out on an industrial scale. This applies to both the discontinuous as well as for the continuous procedure. In the latter Case are alcoholate and chlorocarboxylic acid ester at the same time suspended in a solvent, for example toluene, and continuously pumped into a reactor that is set to reaction temperature « temperature is warmed up. The condensation takes place very quickly and the further work-up takes place according to conventional methods.

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Trial examples

1) Place in a 1 liter round bottom flask with a stirrer «attached 1 * 0 cm Vigreux column and dephlegmator 120 g of sodium methylate and 500 ml of toluene. The mixture is brought to 100 ° C. with stirring heated. 329 g of ethyl 2-methyl-it-chlorobutyrate are then slowly added dropwise over the course of one hour, in the same mass the azeotropic mixture of toluene-CHOH is distilled overhead from (bp. 75 - 78 ° C). The mixture is heated until the transition temperature has reached 110 ° C. (30 minutes). Now you cool off, washed with water, neutralized, separates the phases, dries the toluene solution and distills it on a 2 m Vigreux column at normal pressure. After the flow (toluene) the i-methyl-cyclopropyl-carboxylic acid ethyl ester is distilled at bp 143 ° C. Quantity 233.4 g »corresponding to 91.2 # of theory

In a k 1tr. flask 2 2) Place ltr. Toluene and 486 g sodium methylate. The mixture is heated to 100 ° C. while stirring. Then 1,092 g (= 8 mol) of methyl methyl chlorobutyrate are added dropwise over the course of 2 hours, the toluene-methanol azeotrope being distilled off. The mixture is heated for a further 2 hours, now a solution of 320 g of NaOH in 1 liter is added dropwise. Add CH OH and reflux for 2 hours. You cool off and put at 20 ⁰ C with concentrated hydrochloric acid to pH 2. The mixture is extracted twice with toluene. The extract is dried, evaporated in vacuo at 30 ° C. and then fractionated at 12 mm Hg. The cyclopropanecarboxylic acid distills at bp _{12 75-76 ° C.} Quantity 736 g, corresponding to 92% of the theory.

3) 150 g of sodium ethylate are added to 600 ml of toluene and the mixture is heated with stirring to 100 ° C. Now ^ -Chlorcaproic acid ethyl ester is added dropwise within 60 minutes. Simultaneously

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the toluene-ethanol azeotrope is distilled off. According to the usual Work-up is fractionated on a 2 m Vigreux column distilled. The ethyl 2-methylcyclopropanecarboxylate distills at a boiling point of 157 ° C. Quantity 228.1 g = 89 * 1% of theory.

k) 500 ml of toluene and 84 g of potassium methylate are placed in a 1 liter round bottom flask. The mixture is brought to reflux temperature. At this temperature, 150.5 g of methyl p-methyl-j ^ -chlorobutyrate are added dropwise over the course of 30 minutes. The toluene-methanol azeotrope is distilled off at the top of a column to the same extent. The mixture is then cooled, 300 ml of water are added to the mixture and the mixture is stirred vigorously, the toluene solution is then separated off, dried and distilled on a 2 m packed column with a dephlegmator with strong reflux. 2-Methylcyclopropanecarboxylic acid methyl ester distills at a boiling point of 131 ° C. Quantity: 99 »1 g» corresponding to $ 86.8> d.Th. .

5) Add '»00 ml of chlorobenzene and 120 g sodium t-butoxide. The mixture is refluxed heated, then 178.5 g of "I ^ -Methyl-: i ^ -chiorvaleric acid ethyl ester are added dropwise added within 45 minutes, At the same time, a mixture of chlorobenzene / t-butanol is distilled away. Work-up yields 122.1 g of ethyl 2,2-dimethylcyclopropanecarboxylate. Bp 86 - 87 ° C, yield 86 # of theory.

6) 1000 ml of BenzoJ and 374 g are placed in a 2 liter flask Sodium t-amylate (= 2.2 Mo]). The mixture is taking Heated to reflux. Now slowly add 329 g of J) -ChI or-

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butyric acid isopropyl ester added. At the same time, the t-amyl alcohol / benzene azeotrope is distilled off (three hours). Work-up gives 233t of ¹ S isopropyl cyclopropanecarboxylate, boiling point 14O - 1 ^ 1 ° C, yield 91.1% of the theory.

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Claims (5)

7227 SB ΡΑΤ / Dr No-Jo GERMAN GOLD AND SILVER SCHEIDEANSTALT FORMERLY ROESSLER 6OOO Prankfurt (Main), Weissfrauenstrasse 9 Claims t \ ■
) Process for the Cydisierung von ^ "- Chlorcarbonsäureestem der general formula I. ^R l »? 2? 1 Cl-CCC- COOR (i) III R R H in which R, R-, R ₂ , R ~, R ₄ , and R_ are identical or different and represent a straight or branched alkyl radical having 1 to 4 carbon atoms or, with the exception of R, can also represent a hydrogen atom, optionally substituted cyclopropanecarboxylic acids and their esters of the general formula II «3/2 R | ^ X (11) ^H ^ c c - cooR in which the symbols ο R to R ^ have the meaning given above have, and R can also stand for a hydrogen atom, with the help of a basic condensation agent and, if necessary, subsequent saponification of the ester, 909820/0424 ORIGINAL INSPECTED draws that an anhydrous alkali metal alcoholate is used as the condensing agent, the cyclization is carried out in an inert organic solvent and the
Alcohol forming the reaction is continuously distilled off. 2) The method according to claim 1, characterized in that an alcoholate of an aliphatic alcohol having 1 to 5 carbon atoms, in particular sodium or potassium methylate or ethylate, preferably sodium methylate, is used. 3) Method according to claims 1 or 2, characterized in that that benzene, xylene or preferably toluene is used as the inert organic solvent. k) Process according to claims 1 to 3, characterized in that the alkali metal alcoholate in greater than the stoichiometric amounts, preferably in an excess of
10 to 25 #, begins. 5) Process according to claims 1 to k, characterized in that the cyclopropanecarboxylic acid esters are saponified with alcoholic alkalis and the acid is isolated. 909820/0424