DE1768704C - - Google Patents

Description

The patent 1518 959 relates to a method for Preparation of basic substituted cyclohexenes of the general formula

CO ₂ R ₃

wherein R ₁ and R ₂ , which can be the same or different, a lower alkyl radical or two alkylene radicals linked to one another to form a heterocyclic ring and R ₃ denotes a methyl, ethyl, n-propyl and n-butyl group, characterized in that at room temperature or slightly elevated temperatures butadiene-! 1.3) of the general formula

N - CH = CH - CH = CH,

with an atropic acid ester of the general formula

C _n H ₅ COOR ₃

CH,

30th

35

be reacted in the absence of a solvent. The reaction product is separated off there by forming the hydrochloride and converting it to the free base.

Patent 1,618,476 describes a process for separating an isomer mixture composed of Sc-dimethylamino- ^ phenyMc-carbäthoxyl'-cyclohexene and 3t-dimethylamino-4-phenyMt-carbethoxyl'-cyclohexene into the individual compounds. This process is based on the fact that after the reaction between 1-dimethylaminobutadiene (1.3) and ethyl atropate, the mixture obtained. consisting of about 25% 3-trans-dimethylamino-4-phenyl-4-trans-carbäthoxy-I ¹ -cyclohexene. 65% 3-cis-dimethylamino-4-phenyl-4-cis-carbethoxyl'-cyclohexene. 5% ethyl 2-phenyl-3-dimethylaminöpropionate and dark impurities, the main amount of 3-cis-dimethylamino-4-phenyI-4-cis-carbalhoxy-I'-cyclohexene is precipitated in hydrochloric acid solution with aqueous zinc chloride solution in the form of a zinc complex .

From the aqueous hydrochloric acid phase, the entire base portion is then released by means of ammonia solution and, after conversion into the hydrochloride, subjected to purifying crystallization processes. This process allowed for the first time the semi-industrial production of 3-tians-dimethylamino-4-phenyl-4-trans'carbethoxy-I ¹ -cyclohexene. After the separation of 3-cis-DimethyIamino-4-phenyl-4-cis-carbethoxy-l'-cyclohexene Ron batches, the following average analytical values were obtained on a semi-industrial scale: 3-trans-DimethyIamino-4-phenyl-4- trans-carriithoxy- I ¹ • cyclohexene: 80%; 3-cis-Dimethylamino-4-phenyl-4-cis-carbethoxy-. ^L -cyclohexene: 10%; Ethyl 2-phenyl-3-dimethylamino-propionate: 5% and 5% basic, colored impurities. In practice it has now been shown that by repeated recrystallizations of the hydrochloride mixture, although the remaining 3-cis-dimethylamino-4-phenyl-4-cis-carbätboxy-S ¹ -cyclohexene content could be reduced to 2% and below, 2- Ethyl phenyl-3-dimethylamino-propionate and the salts of the colored, basic impurities, however, stubbornly accompanied ^{the 3-trans · dimethylamino-4-phenyl-4-trans-carbethoxy-J 1 -cyclohexene.} In order to obtain a pure 98% 3-trans-dimethylamino-4-phenyl-4-trans-carbäwhoxy- ^ l ¹ -cyclohexene, a high vacuum cleaning in a molecular distillation apparatus was necessary, followed by high-loss crystallization processes; the recovery of the 3 - ^^ 5-011 ^ 11 ^ 13111 ^ 0-4 ^ 116 ^ 1-4-trans-carbäthoxyl'-cyclohexene portion from the mother liquors proved to be unprofitable. By means of this method it is therefore not possible, mainly for economic reasons, to produce an excellent quality of 3-trans-dimethylamino-4-phenyl-4-trans-carbethoxy-I ¹ -cyclohexene (content around 99.9%) on an industrial scale Surprisingly, it has now been found that naphthalene-1,5-disulfonic acid is a specific precipitant for 3-trans-dimethylamino ^ -phenyl ^ -trans-carbäthoxy-I ¹ -cyclohexene, which allows the isomer of interest 3-tΓans- Dimethylamino-4-phenyl-4-trans-carbethoxy-, l'-cyclohexene in the presence of any concentration of 3-cis-dimethylaminu-4-phenyl-4-cis-carbäthoxyl'-cyclohexene, 2-phenyl-3-dimethylaminopropionate or the called basic impurities to be deposited in almost quantitative yield as pure crystals.

The invention thus relates to a process for the separation of 3-trans-dimethylamino-4-phenyl-4-trans-carbethoxyl'-cyclohexene from a mixture obtained by reacting 1-dimethylaminobutadiene (1.3) and atropic acid ethyl ester has been obtained by salt formation and then transfer of the formed salt with alkali metal hydroxides in the free base according to Patent 1518 959. This is characterized is. that one carries out the salt formation with naphthalene-1 ^ -disulfonic acid in lower alcohols.

According to the invention, naphthalene-1,5-disulfonic acid forms with J-trans-dimethylamino ^ -phenyM-transcarbethoxyl'-cyclohexene in lower alcohols, especially in methanol. Ethanol and isopropanol. an extremely poorly soluble double salt of the composition [('10HsS ₂ Of ₁ ] [C ₁ -H ₂₃ NO ₂ I ₂ with the melting point 244 to 245 ° C. (decomposition).

Gross Formula: C ₄₄ H ₅₄ N ₂ O _1n S ₂ : Molecular Weight: 834.84.

Calculated ... C 63.30, H 6.52, N 3.38, S 7.68%; found .... C 62.94, M 6.24. N 3.32, S 7.43%.

The advantage of the direct separation of the only interesting 3-trans-dimethylamino-4 «phe · ny 1-4-trans-carbethoxy- l'-cyclohexene compared to the From earlier methods it is evident: According to the earlier process, all impurities accumulate together with 3 -trans * Dimethylamine) - 4 * phenyl 4-trans-carbethoxy * l'-cyclohexene; with this one all accompanying substances remain along with the undesirable isomers in the mother liquors.

I 768 704

In this way it becomes possible to use 3-trans-dimethylamino-4-phenyl-4-trans-carbethoxy-. | ^{Separate l} -cyclohexene on an industrial scale. So z. B, can be worked with 20 times the amounts of the following example.

example

A solution of 1.5 mol (432 g) of naphthalene-1,5-disulfonic acid in 3 l of ethanol is prepared slight warming. It is now the content of S-trans-Dimethylamino ^ phenyl ^ trans-carbäthoxyl'-cyclohexene of the raw base to be felled. Then the amount of raw base is calculated, which

Includes phenyl-4-trans-carbäthoxy-, l ^{l-cyclohexene} - 2 mol (546 g) 3 - trans - dimethylamino -. 4 The determined amount of crude base is dissolved in 3 l of ethanol and mixed with the naphthalenedisulfonic acid solution at room temperature. When the well-sedimenting salt begins to separate out, the mixture is stirred for a few hours at 0 to 5 ° C. The heavy, colorless salt can be siphoned off effortlessly; it is washed once with ethanol and air-dried. The yield is the content of

3 - trans - dimethylamino - 4 - phenyl - 4 - trans - carb-

ethoxy-j'-cyclohexene is almost quantitative accordingly. The total content of 3-cis-DimethylamJno-4-phenyl-4-cis-carbäthoxy-, l ^{l-cyclohexene} and 2-phenyl - 3 - dimethylamino - ethyl propionate and

Impurities is below 0.5%. If necessary, the double salt can be recrystallized from 90% ethanol will.

The double salt can be in the pure 3-trans-dimethylamino-4-phenyl-4-trans-carbäthoxy- / l ^{l-cyclohexene}

ίο by slurrying in water and treating be transferred by means of 2N NaOH.

Claims (1)

Claim: Process for the separation of 3-trans-dimethylamino-4-phenyl-4-trans-carbäthoxy- / l'-cy- clohexene from a mixture obtained by reacting 1-dimethylaminobutadiene (1,3) and Atropic acid ethyl ester has been obtained by salt formation and then transferring the formed salt with alkali metal hydroxides in the free base according to patent 1518 959, thereby characterized in that one is the salt formation with naphthalene-1,5-disulfonic acid in lower alcohols.