DE3900865C1 - Process for the preparation of 2-chloroethylamine hydrochloride - Google Patents

Abstract

The invention relates to a process for the preparation of 2-chloroethylamine hydrochloride by reacting 2-hydroxyethylamine hydrochloride with thionyl chloride, using, as solvents, carboxylic acids in substoichiometric amounts relative to the amount of 2-hydroxyethylamine hydrochloride employed.

Description

The invention relates to a method for producing 2-chloroethylamine hydrochloride (1) by reacting 2- Hydroxyethylamine hydrochloride (2) with thionyl chloride in Presence of a solvent.

Because (1) an important intermediate in the industrial is organic chemistry, this implementation is in-depth been examined.

In Ro 55 946, JP 7 60 80 822 and JP 7 51 29 505 is a Production process (A) described in which (2) first with HCl at high temperatures with removal of the water formed in the reaction and then with thio nyl chloride is implemented. Toluene is used as the solvent (JP 7 60 80 822, JP 7 51 29 505) or xylene or Mesitylene (JP 7 51 29 505) used. This procedure is (A) however, it has very large corrosion problems.

In another method (B), (2) is exclusive reacted with thionyl chloride, this reaction in Benzene (Metody Poluch. Khim. Reaktivov Prep. 1969, No. 2, 81-3), water-insoluble solvents (GB 14 30 882) or water-insoluble solvents such as Benzene, toluene or xylene in the presence of a catalyst such as DMF (DE 24 18 743) is carried out.  

If method (B) does not add DMF, the implementation is not quantitative and purification of (1) required. On the other hand, DMF in Presence of thionyl chloride carcinogenic dimethyl carbamic acid chloride (list of MAK values, MAK section III A2, 1988) form, which in the aqueous work-up of Reaction mixture is implemented to dimethylamine and CO₂. However, dimethylamine cannot be easily obtained from (1) separate and also interferes with many implementations, such as for example the manufacture of sulfonamides.

The methods described in the literature for Manufacture of (1) are thus with considerable shortcomings afflicted.

It therefore existed because of the meaning of (1) important intermediate in industrial organic Chemistry an urgent need, a process for that Manufacture of (1) to find the disadvantages of one low purity of the product and / or more serious Corrosion problems and / or hazardous to health Has no by-products.

Surprisingly, it has now been found that the implementation of (2) with thionyl chloride in the presence of an under stoichiometric amount of carboxylic acid, based on the amount of (2), these requirements are excellently met. These Implementation is easy to handle, there is no corruption problems and an addition of DMF is not required. The product falls in high yield and very pure and is also directly to further implementations suitable because the carboxylic acid contained in the product many implementations, such as B. the manufacture of sulfone amid, do not bother. The method according to the invention is inexpensive, environmentally friendly and can easily be transferred to the production scale.  

The invention accordingly relates to a method for Production of 2-chloroethylamine hydrochloride by Reaction of 2-hydroxyethylamine hydrochloride with thionyl chloride in the presence of a solvent, where as An aliphatic carboxylic acid or a solvent aliphatic carboxylic acid mixture with chain lengths of 1 to 10 C atoms each in substoichiometric amounts, based on the amount of (2) used.

Methods are preferred in which low-chain Carboxylic acids with chain lengths of 1 to 4 carbon atoms as Solvents are used. Very particularly preferred is the use of formic acid and acetic acid as Solvent.

Methods in which the ratio γ of the amount of carboxylic acid and the amount of (2) is between 0.05 and 0.5 are further preferred. Processes in which the quantitative ratio γ is between 0.1 and 0.25 are very particularly preferred.

Aliphatic carboxylic acids are suitable as solvents with chain lengths of 1 to 10 carbon atoms, each alone or can be used in a mixture with one another. However, low-chain carboxylic acids are preferred. An example of preferred carboxylic acids is in the called individual: formic acid, acetic acid, propionic acid, Butyric acid, also isobutyric acid, n-valeric acid and pivalic acid.

Formic acid, acetic acid, propion are particularly suitable acid and butyric acid. These carboxylic acids are in opposition set of the previously used for the production of (2),  water-immiscible solvents in every ver Ratio miscible with water.

Formic acid and acetic acid are very particularly suitable, but especially acetic acid.

The addition of carboxylic acid to (2) causes a melting point lowering the mixture. A warming of the mixture to temperatures of 20 to 120 ° C, in particular however, at 50 to 70 ° C is therefore sufficient to achieve the Reaction of (2) with thionyl chloride in the liquid phase perform.

The ratio β from the amount of thionyl chloride used and the amount of (2) can be 1.0 to 1.6. However, an excess of thionyl chloride is preferably used and β is between 1.1 and 1.5, in particular between 1.2 and 1.3.

To the mixture of (2) and the carboxylic acid thionyl chloride is slowly added dropwise. The dropping time can be up to 20 hours, but is preferred chosen between 2 and 5 hours.

Then the reaction mixture at temperatures of 20 to 120 ° C, but in particular 50 to 70 ° C stirred. The Reaction time can be up to 24 hours however usually chosen to be 2 to 6 hours. There are but shorter or longer reaction times are also possible.

After completion of the reaction, the preferred room temperature cooled reaction mixture water or salt acid added. Dilutions are preferred which creates a 30 to 80 vol .-% solution of (1). 50 to 70% by volume solutions are particularly preferred.  

The solutions thus obtained are on the one hand stable in storage and on the other hand directly for further implementations suitable. In addition, these solutions can also be high pure (1) can be isolated by crystallization.

Are longer-chain carboxylic acids (e.g. hexanoic acid) as Solvent used, takes place after dilution Water or hydrochloric acid phase separation instead. The Carboxylic acid can then be easily separated and given if purified again by distillation.

In the process according to the invention, thionyl chloride slowly added dropwise to a mixture, which from (2) and one in substoichiometric amount carboxylic acid:

HOC₂H₄NH₂-HCl + SOCl₂ + CH₃COOH → ClC₂H₄NH₂-CHl + SO₂ + CHl + CH₃COOH I

This reaction procedure prevents the formation of acid halides according to equation II and further from amides according to Equation III or esters according to equation IV despite Ver use an excess of thionyl chloride completely avoided:

RCOOH + SOCl₂ → RCOCl + HCl + SO₂ II

RCOCl + HOC₂H₄NH₂ → RCONHC₂H₄OH + HCl III

RCOCl + HOC₂H₄NH₂ → RCOOC₂H₄NH₂ + HCl IV

R = rest, e.g. B. alkyl

This can be seen, for example, from 1 H-NMR spectra of the crude, not processed reaction mixture, which none Indications of amides or esters formed during the reaction give, be inferred.

The implementation is almost quantitative. There will be sales achieved by over 99.5%, in addition to DE-OS 24 18 743, where sales of 98% are given, no addition of DMF is required.

The resulting in the method according to the invention crude, optionally diluted with water or hydrochloric acid Reaction mixture is due to the high purity of the gebil also (1) directly, i.e. H. without additional purification, suitable for further implementations.

The vinegar present in the reaction mixture interferes with this acid in many reactions. This is about the Case in the manufacture of sulfonamides according to Reak equation V:

ClC₂H₄NH₂-HCl + CH₃SO₂Cl + 2 NaOH → CH₃SO₂NHC₂H₄Cl + 2 NaCl + 2 H₂O V

The sulfonamides produced in this way are important auxiliaries fabrics for making photo chemicals.

The after the extraction of (1) or from (1) in Presence of product formed from the acetic acid Reaction mixture remaining acetic acid solution can be completely broken down in biological sewage treatment plants. The method according to the invention is thus to a high degree environmentally friendly and also extremely inexpensive because a treatment of the residue solution with the aim of Carboxylic acid recovery can be omitted.  

(1) is an important intermediate in industrial organic chemistry and plays for example at the Manufacture of drugs, pesticides, Dyes and photo chemicals play an important role. The considerable need for (1) can therefore be met by inventive method that the inexpensive and environmentally friendly production (1) in a very pure form and high Yield allowed, much better than with the known manufacturing processes are satisfied.

The following examples are preferred embodiments Forms of the manufacturing process described. The Examples are intended to explain the process according to the invention.

Manufacturing examples Example 2

A mixture of 390 g (2) and 44.8 g of acetic acid is heated to 60 ° C. 602.4 g of thionyl chloride are added dropwise to the viscous mass in 3.5 hours. The viscous mass quickly turns into an easily stirrable oil. The mixture is stirred for a further 3.5 hours at 60 ° C. and then cooled to room temperature. The mixture is then diluted with 172 ml of water and a 68.0% strength aqueous solution of (1) is obtained which is stable in storage and is also suitable directly for further reactions.
The yield is 99.1% of theory. Th.

Example 2

A mixture of 270.8 g (2) and 23.9 g of formic acid is heated to 70 ° C. 418.4 g of thionyl chloride are added dropwise to the viscous mass in 3.5 hours with stirring. The viscous mass quickly turns into an easily stirrable oil. The mixture is stirred for a further 3.5 hours at 80 ° C. and then cooled to room temperature. Then it is diluted with 120 ml of water. An aqueous solution of (1) is thus obtained which is stable in storage and is also suitable for further implementations.
The yield is 99.0% of theory. Th.

Usage example

170.7 g of the aqueous solution obtained in Preparation Example 1 Solution of (1) are directly at a pH of 8 with 126.0 g of methanesulfonic acid chloride reacted. The so obtained 1-chloro-2-methylsulfonamidoethyl hydrochloride is used in a pH of 7 with 127.1 g of N-ethyl-m-toluidine puts. N-ethyl-N-2- (methylsulfonamido) ethyl m-toluidine formed, which is obtained in a very pure form and has a purity of 99% (HPLC) without purification.

Claims (5)

1. A process for the preparation of 2-chloroethylamine hydrochloride by reacting 2-hydroxyethyl amine hydrochloride with thionyl chloride in the presence of a solvent, characterized in that an aliphatic carboxylic acid or an aliphatic carboxylic acid mixture with chain lengths of 1 to 10 C- is used as the solvent. Atoms in substoichiometric amount, based on the amount of 2-hydroxyethylamine hydrochloride used. 2. The method according to claim 1, characterized in that that carboxylic acids with chain lengths of 1-4 carbon atoms starts. 3. The method according to claim 2, characterized in that you use formic acid and / or acetic acid. 4. The method according to claim 1-3, characterized in that the ratio γ from the amount of carboxylic acid and the amount of 2-hydroxyethylamine hydrochloride is between 0.05 and 0.5. 5. The method according to claim 4, characterized in that the quantitative ratio γ is between 0.1 and 0.25.