DE1072988B - - Google Patents

Description

GERMAN

It is known that cycloheptene- (l) -carboxylic acid- (l) obtained when using l-chlorocycloheptanoic acid Sodium hydroxide solution boils or treated with alcoholic alkali (cf. J, Chem. Soc. [London], 1953, p. 2202). Furthermore, from the German interpretation document 1005 062 known that the implementation of 2,8-dihalocyclooctanone with aqueous alkali metal hydroxides to cycloheptene- (l) -carboxylic acid- (l), while in the Treatment of 2,8-dihalocyclooctanones with anhydrous alcoholic alkali hydroxide or alkali alcohol lat solutions containing the esters of cycloheptene (l) carboxylic acid (l). After all, it is known that upon exposure from aqueous alkaline solutions to 1,6-dihalocyclohexanones Cyclopentanolcarboxylic acid is obtained as a reaction product (cf. Lieb. Ann. d. Chemie, Vol. 414, 1918, p. 313).

It has now been found that 2-chloro- or 2-bromocycloheptene- (l) -carboxylic acid- (l) is obtained if 2,2,8-trichloro- or 2,2,8-tribromocyclooctanone with alkali or alkaline earth metal hydroxides in aqueous, aqueous alcoholic or alcoholic medium and by acidifying the reaction mixture with a Mineral acid that releases 2-chloro- or 2-bromocycloheptene- (l) -carboxylic acid- (l).

The 2,2,8-trichloro- and 2,2,8-tribromocyclooctanone are not yet described in the literature. The connections can be obtained easily and in a simple manner, for example by adding chlorine to cyclooctanone or bromine in at least the amount calculated for the introduction of 3 halogen atoms, advantageously one Excess of the halogen in the presence of solvents such as carbon tetrachloride, chloroform, methylene chloride or alcohols, e.g. B. methanol, optionally under irradiation with UV light and / or after Addition of activators, e.g. B. iodine, at temperatures from about 0 to + 10 ° C can act.

Of the alkali and alkaline earth metal hydroxides which can be considered as further reaction components sodium, potassium and calcium hydroxide should be mentioned in particular. The hydroxides become useful applied in dissolved, optionally suspended form. As a solvent or suspending agent, in addition to Water also alcohols or their mixtures with water are used. Particularly suitable alcohols are, for. B. low molecular weight Alkanols such as methanol, ethanol and n- or isopropanol. Other alcohols, e.g. B. cycloaliphatic Alcohols, such as cyclopentanone cyclohexanol or cyclooctanol, or aromatic alcohols such as benzyl alcohol or phenol and cresol are also useful. as Solutions of alkali or alkaline earth metal hydroxides can be used with any hydroxide content will. It is advisable to choose the concentrations between about 1 to 50 percent by weight. Advantageous one works with about 1 to 10 weight percent, process for the production

of 2-chloro or 2-bromocycloheptene

(1) -carboxylic acid- (1)

Applicant:

Aniline & Soda Factory in Baden

Corporation,

Ludwigshafen / Rhine

Dr. Hans Moell, Ludwigshafen / Rhine,

and Dr. Nikolaus von Kutepow, Karlsruhe-Rüppurr,

have been named as inventors

especially with about 3 to 10 weight percent solutions. The hydroxides are advantageous for the implementation used in such an amount that there are about 3 moles of hydroxide for 1 mole of trihalocyclooctanone. It is advisable to work with a little more, e.g. B. with an excess of about 10 to 20 percent by weight. Fewer than about 3 moles of hydroxide per mole of trihalocyclooctanone to use is inconvenient in that the conversion of the trihalocyclooctanone remains incomplete. A larger excess than that already mentioned can be used.

The implementation takes place z. B. in such a way that one in an aqueous, aqueous-alcoholic or alcoholic Solution or suspension of the alkali or alkaline earth metal hydroxides a 2,2,8-trihalocyclooctanone in solid or dissolved form enters and the two reactants can act on each other until no more Implementation more done. In general, the reaction is complete after about 15 to 20 minutes. One can but also bring about the reaction by bringing the reaction components together in a different order. For example, the alkali or alkaline earth metal hydroxide can be added to an alcoholic solution of the 2,2,8-trihalocyclooctanone Apply solid or dissolved in water and / or alcohols. As alcohols for dissolving the trihalocyclooctanone the same alcohols can be used as those for the preparation of the solutions the alkali or alkaline earth hydroxides are mentioned.

The reaction temperatures chosen are particularly advantageously between about 0 and 85.degree. C. However, it is also possible to work at higher temperatures, for example at temperatures above 85 to about 150.degree. C. _{1 in} which case, however, the work may be carried out in closed conditions

909 709/465

³ 4

Vessels may be required. As the reaction occurs, the reaction mixture containing the potassium salt low temperatures, such as about 0 to + 15 ° C, already contains the 2-bromocycloheptene- (l) -carboxylic acid- (l) acidified 2η-sulfuric acid sufficiently quickly and with strong heat development. The failing, color drains, it is advantageous to suck them loose crystals at these temperatures, wash them with water to begin and in the course of the reaction then recrystallized to 5 and from water. 26 parts are obtained higher temperatures, e.g. B. about 80 ° C to pass. 2-bromocycloheptene- (l) -carboxylic acid- (l) from the melting point The 2-halogen point in the reaction mixture is 115 ° C. The yield is 86% of theory. cyclohepten- (l) -carboxylic acids- (l), which in the mixture as the 2,2,8-tribromocyclooctanone was in the way Alkali or alkaline earth salts are initially present, obtained in the usual way by adding 200 parts of cyclooctanone in 400 parts Way by acidifying with a mineral acid such as hydrochloric ίο carbon tetrachloride at 0 to 5 ° C with stirring acid, phosphoric acid or sulfuric acid, in free form 770 parts of bromine in 250 parts of carbon tetrachloride. dissolves, entered the precipitated crystals after 12 hours

The by-product obtained in the process is aspirated and washed out with a little carbon tetrachloride.

Cycloheptanone, which by the action of the hydroxides The yield of tribromocyclooctanone was

is formed on the Trihalogencyclooctanone. The 15,472 parts correspond to 82% of theory. The product

The amount of by-product increases with increasing melt at 111 to 112 ° C.

Reaction temperatures, especially above. .

8O ⁰ C, as well as when working with higher hydroxide Example 2

concentrations in the mixture to be converted. In 150 parts of a 20% alcoholic sodium

The 2-halocycloheptene- (l) -carboxylic acids- (l) are 20 hydroxide solution with stirring within except for the 2-bromocycloheptene- (l) -carboxylic acid- (l) new 20 minutes 50 parts of 2,2,8-tribromocyclooctanone incorporated compounds and are valuable starting materials for wearing while one is cooling from the outside, so that the Tem production of pharmaceuticals. As an intermediate product, the temperature does not rise above 10 ° C. The reaction can be used, for example, for the preparation of cyclomix is slowly heated to the boil and 3 hours heptanone can be used. 25 boiled on the reflux condenser. After it has cooled down

The 2-chlorocycloheptene- (l) -carboxylic acid- (l) is new. the precipitated potassium bromide sucked off and with

The 2-bromocycloheptene- (l) -carboxylic acid- (l) could be washed out of alcohol. After the alcohol has evaporated

long obtained only from the poorly accessible dibromocyclo- hols from the combined alcoholic filtrates

heptenocarboxylic acid by the action of zinc dust in a crystal pulp, which is dissolved in a little water.

Presence of alcoholic hydrochloric acid can be obtained. The aqueous solution is diluted with dilute sulfuric acid

(See reports of the German former Ges., Vol. 31, 1898, acidified, whereby the 2-bromocyclohepten- (l) -carbon-

P. 2244). acid (l) separates. They are separated from the mother liquor

The 2-chloro- and 2-bromocyclohepten- (l) -carboxylic acids and recrystallize them from water. You get

are valuable starting materials for the production of 27 parts with a melting point of 115 ° C. The yield is

Pharmaceuticals and own bile flow-increasing 35 contributes 89.5% of theory. From the aqueous mother liquor

Effect. As an intermediate they can, for example, be 3 parts of cycloheptanone, the phenylhydrazone

also used for the production of cycloheptanone can be isolated.

will. -r · · 1 ¹ ^

. That the inventively used, so far .Example 0

unknown Trihalogencyclooctanone with aqueous or 40 250 parts of chlorine are converted into a solution of 126 parts of alcoholic alkali to halogenocycloheptenecarbon cyclooctanone in 400 parts of chloroform at 0 to +5 ⁰ C acids is surprising. One would have expected initiated. After evaporation of the solute, it is obtained that all halogen atoms are attacked by the strong alkalis by means of distillation under reduced pressure. Curiously, however, is a 145 parts of 2,2,8-Trichlorcyclooctanon- (l), bp. 110 _OL4 halogen atom in the 2,2,8-Trihalogencyclooctanonen 45-114 ° C. After recrystallization of the product much stronger than the other two bound , so from petroleum ether it melts at 88 to 90 ° C. The extent that it is not or only to a lesser extent under booty is 79.6% of theory,
subject to the reaction conditions according to the invention of the 12 parts of the hydrolysis prepared in the above manner. One has to assume and expect 2,2,8-Trichlorcyclooctanons- (l) have to be in a pressure that the reaction to an oxycyclohepten- 5 ° vessel with 1000 parts of an aqueous 1% aqueous carboxylic acid or that of this enol form is derived. Sodium hydroxide solution is heated and leads to tenden /? - keto acid for 10 hours. Surprisingly, 150 ° C. is maintained. After cooling, however, the halogenocycloheptenic acids are relaxed. Furthermore, the vessel and acidifies the reaction mixture with 2N salt also unexpectedly that does not correspond to that of the acid. The aqueous mixture is extracted with ether, known in German Auslegeschrift 1 005 062. The ethereal extract is dried with anhydrous sodium sulfate and dihalocyclooctanones are dissolved with alcohol, and the drying agent is filtered off. The filtrate formed from the alkali hydroxides, the cycloheptenic acid esters, is evaporated off the ether. There remain 8 parts, but also in this case the halocyclo- 2-chlorocycloheptene- (l) -carboxylic acid- (l) with a melting point of 95 ° C heptenecarboxylic acids are obtained. return. The yield is 88% of theory.

The parts mentioned in the examples are 60% by weight.

share. Example 4

For example 72 parts of a 30 weight percent lithium hydroxide

solution made using 20% aqueous

In 300 parts of a 10% aqueous Kaüumhydroxyd- Ethanol was prepared in a stirred vessel

solution, 50 parts of 2,2,8-tribromocyclooctanone are cooled to within 65.degree. Over the course of 2 hours, the

half of 15 minutes with stirring and weakly cooled solution 115 parts of 2,2,8-trichlorocyclooctane

Cooling entered. The mixture is slowly heated to on- (l). Ice cooling is used for this

75 ° C and continues stirring after everything is done to ensure that the temperature does not exceed ^{+5 0 C.}

Tribromocyclooctanone has dissolved, another 4 hours at After. The mixture is then stirred in

75 ° C. After cooling to room temperature 7 ° 4 hours at room temperature. One acidifies the

then mix with 10 weight percent phosphoric acid and work it in the manner described in Example 1 on. 67 parts of 2-chlorocycloheptene- (l) -carboxylic acid- (l) with a melting point of 95.degree. To 96.degree. C. are obtained. The yield corresponds to 77% of theory.

Claims (1)

PATENT CLAIM: Process for the preparation of 2-chloro- or 2-bromocyclohepten- (l) -carboxylic acid- (l), thereby ge ίο indicates that 2,2,8-trichloro- or 2,2,8-tribromocyclooctanone is reacted in a manner known per se with alkali metal or alkaline earth metal hydroxides in an aqueous, aqueous-alcoholic or alcoholic medium and the reaction mixture is acidified with a mineral acid 2-chloro- or 2-bromocycloheptene - ^ - carboxylic acid-tl) releases. Considered publications:
German interpretation document No. 1 005 062. © 90Ϊ 709/465 1.60