WO2010108817A1

WO2010108817A1 - Method for producing n,n`-lactic acid dialkylamide using ionic liquids

Info

Publication number: WO2010108817A1
Application number: PCT/EP2010/053349
Authority: WO
Inventors: Andreas Lanver
Original assignee: Basf Se
Priority date: 2009-03-26
Filing date: 2010-03-16
Publication date: 2010-09-30

Abstract

The invention relates to a method for producing N,N`-lactic acid dialkylamides in a one-pot reaction, said N,N'-lactic acid dialkylamides being obtained from an ionic liquid.

Description

A process for preparing N, N ^{'-Milchsäuredialkylamid} via ionic liquids

description

The invention relates to a process for the preparation of N, l \ T-Milchsäuredialkylamiden in a one pot reaction, wherein the N, N ^{'-Milchsäuredialkylamide} is obtained from an ionic liquid.

Lactic acid amides, especially N, NT-lactic acid dimethylamide, can be used as organic solvents.

N ₁ N ^' - Milk acid dimethylamide

In WO 2007/107745 they play an important role in particular as a formulation agent in agrochemical applications as environmentally friendly ingredients.

The synthesis of N, N ^{'-Milchsäuredimethylamid} described in the literature and this can be made in different ways. Preferred educts are the methyl and ethyl esters of lactic acid, as well as dilactide. It can be achieved under mild reaction conditions such as room temperature very good yields.

Thus, in Bull. Chem. Soc. 1989, 62, 3038-3040 by Y. Kobayashi et al. the synthesis starting from the ethyl ester of lactic acid dimethylamide at a temperature of 70 ⁰ C in a yield of 93% described.

The preparation of lactic acid dimethylamide starting from methyl lactate is described by W.P. Ratchford et al. in JACS 1947, 69, 1911-1914, giving an 86% yield at room temperature and a reaction time of 24 hours.

The prior art has a number of examples in which lactic acid dimethylamide is produced from lactic acid in a multi-step process. Thus, the production of lactic acid dimethylamide in DE-A 4214895 and BL Feringa et al. in Tetrahedron 1994, 50 (40) 11721-1 1728 in a one-pot reaction without isolating the intermediates. One of these methods of preparation is carried out so that the hydroxy group of the lactic acid is first esterified, the carboxylic acid group is then activated by preparation of the chloride or a mixed anhydride, and after the amidation the hydroxy group is deprotected again. Overall, however, this procedure offers no advantages over the preparation of the amide starting from the ester. A disadvantage of all multi-step process is that first functional groups are introduced into the molecule, which are split off again in the next step. Therefore, fall Multistage process either large waste streams, or process technically complex returns are necessary.

WO8705605 describes a process for the preparation of the corresponding lactamides according to Scheme 1.

Here, high-boiling amines are reacted in non-pressurized processes. The resulting water is distilled off azeotropically from the reaction mixture.

Scheme 1: Synthesis of N-lactoctadecylamide

In US-A 4021572, the reaction of lactic acid with dimethylamine is claimed to a reaction product not described in detail. The reaction is carried out at room temperature in aqueous or alcoholic solution. The formation of a lactamide is not described, but only the formation of a salt of lactic acid and the amine used.

WO-A 9730964 describes the amidation of lactic acid salts under CO 2 pressure. It is disclosed in the specification that amines can also be present in the esterification of lactic acid salts (sodium or calcium salt) in the presence of CO 2 in order to form the corresponding amides. Examples of such an implementation do not exist.

According to a regulation of W.P. Ratchford et al. in J. Am. Chem. 1949, 71, 647-651 poly-lactic acid is reacted with dimethylamine as described in Scheme 2 in a reaction column in countercurrent at 175 ° C. There is obtained a yield of 72%. Disadvantage of this method is that first poly-lactic acid must be prepared by an energy-intensive dehydration of lactic acid. In another journal article by M. M. Shirsalkar et al. in J. Appl. Polym. Be. 1992, 44, 1873-1881, a mixture of diethylamine is heated with lactic acid in toluene and water is removed azeotropically. The yield was not stated. The disadvantages of this method is the use of an organic solvent, which requires further reaction steps to remove.

Scheme 2: Synthesis of N, N ^{'-Milchsäurediethylamid} JP2003-327567 describes the reaction of lactic acid with various amines into amino acids under pressure as disclosed in Scheme 3. According to this prior art, no N, N ^{'-Milchsäuredialkylamid} under pressure is therefore obtained, but it comes to the rearrangement of the nitrogen group and thereby to form the corresponding amino acids or amino acid amide to the. An example given is the production of N-ethylalanine in a yield of 3.1%. The reaction is carried out under pressure at a temperature of 383 ° C in a continuous reactor.

Scheme 3: Synthesis of amino acids from lactic acid (see entry 7)

While the reaction of esters, anhydrides and acid chlorides of lactic acid with dimethylamine can be realized with very high yields under mild reaction conditions, the direct reaction of the free acid with an amine is much more difficult to implement.

The object of the present invention is therefore a process for preparing N, N ^'- to provide Milchsäuredialkylamiden ready, which allows the N, ^N' - Milchsäu- redialkylamide in high selectivity and yield directly in one step without Esterbildung from the lactic acid and the produce each dialkylamine. Another task is to obtain the chiral center in the reaction of enantionmeren pure lactic acids.

This object is achieved by a process for preparing N, N ^{'-Milchsäuredialkylamid} comprising the steps of

a) reaction of a solution containing lactic acid with a solution containing dialkylamine of the general formula R ¹ R ² NH b) holding the solution obtained from step a) at temperatures of 5 to 50 ^° C. for a time in the range from 10 to 120 minute c) subsequent removal of the solvent, d) heating the product obtained from step c) to temperatures in the range from 100 to 250 ^° C. and e) distillation at a pressure in the range from 10 to 200 bar,

where the radicals R ¹ and R ^{2 of} the dialkylamine used are independently selected from the group of methyl, ethyl, n- and iso-propyl. The process according to the invention is advantageous when R ¹ and R ^{2 are} identical.

The process according to the invention is advantageous when R ¹ and R ^{2 are} methyl.

The process according to the invention is advantageous if the lactic acid and the dialkylamine of the general formula R ¹ R ² NH are dissolved in the same solvent

The process according to the invention is advantageous if water is used as the solvent in step a).

The process according to the invention is advantageous if the solvent in step c) is removed by applying a vacuum.

The process according to the invention is advantageous if the lactic acid in the solution containing lactic acid is pure enantionmeren.

In the method of the invention, a solution containing lactic acid is used, wherein the lactic acid is dissolved in a solvent selected from the group of water and aromatic solvents. Preferred aromatic solvents are benzene, toluene and xylene. However, a particularly preferred solvent is water

This solution containing lactic acid is then reacted with R ¹ R ² NH containing solution, wherein R ¹ and R ^{2 are} independently selected from the group of methyl, ethyl, n- and iso-propyl. Preferably, the groups are methyl and ethyl for R ¹ and / or R ² . More preferably, R ¹ and R ^{2 are} identical. Most preferably, R ¹ and R ^{2 are} methyl.

The lactic acid in the lactic acid-containing solution may be both a racemic mixture of (D) - and (L) -lactic acid and an enantionmeren pure lactic acid.

In the implementation of an enantionmer pure lactic acid by the inventive method, the center of chirality is maintained. The R ¹ R ² NH is dissolved in a solvent which is selected from the group of water and aromatic solvents. Preferred aromatic solvents are benzene, toluene and xylene. However, a particularly preferred solvent for the R ¹ R ² NH is water. Most preferably, the R ¹ R ² NH and the lactic acid are dissolved in the same solvent, in particular, very particular preference is given to using water as solvent both for the R ¹ R ² NH and for the lactic acid. The lactic acid-containing solution may have any possible lactic acid concentration. Preferably, the lactic acid concentration in the solution is in the range of 85 to 95%, more preferably in the range of 89 to 94%.

To the cooled to temperatures in the range of 0 to 10 ⁰ C containing lactic acid solution is then added to a likewise cooled to this temperature R ¹ R ² NH containing solution. Both solutions are mixed together. For mixing, any mechanical stirrer known to those skilled in the art is suitable. This solution is left for a time in the range of 10 to 120 minutes, preferably in the range of 20 to 60 minutes at temperatures in the range of 5 to 50 ⁰ C, preferably in the range of 20 to 30 ⁰ C, so that the corresponding Dialkylammoniumlactat has formed in the solvent.

Subsequently, in step c) of the process according to the invention, the solvent is removed. For removal of the solvent, any type of solvent removal known to the person skilled in the art is possible which does not heat the temperature of the dialkylammonium lactate-containing solution above 300.degree. Preferably, the removal of the solvent in vacuo.

The residue is the dialkylammonium lactate ionic liquid. By ionic liquid are meant all salts which melt at atmospheric pressure below 100 ° C.

The ionic liquid obtained from step c) is then heated in step d) of the inventive method to temperatures in the range of 100 to 250 ⁰ C, preferably in the range of 150 to 250 ⁰ C, particularly preferably in the range of 200 to 240 ⁰ C and distilled at a pressure in the range from 200 to 10 mbar, preferably in the range from 50 to 10 mbar, particularly preferably in the range from 50 to 30 mbar according to step g) of the process according to the invention.

The advantage with the process according to the invention is that this process can be carried out in only one reaction vessel and thus as a one-pot reaction does not provide for two stages via the formation and isolation of the ester of lactic acid as described in the prior art. example

20 g of lactic acid (90% in water) are introduced at 1 ° C and treated with dimethylamine (40% in water). The pale yellow solution is heated to RT after about 80 minutes. The water is distilled off under reduced pressure (50 ⁰ C, 20mbar). 25.2 g (0.18 mol) of dimethylammonium lactate (93% yield) were obtained as an ionic liquid (mp: ca. 35 ° C.).

16.6 g (0.123 mol) of Dimethylammoniumlactat thus obtained were heated in an oil bath (200-240 ⁰ C). It was dried under vacuum (50-30 mbar; bottom temperature: 170- 200 ⁰ C; head temperature: 90-1 10 ⁰ C) Milchsäuredimethylamid distilled off as the reaction product.

N, N ^{'-Milchsäuredimethylamid} was obtained with a yield of 40% and a purity of about 70%.

Claims

claims

1. A process for preparing N, N ^{'-Milchsäuredialkylamid} comprising the steps of

a) reaction of a solution containing lactic acid with a dialkylamine of the general formula R ¹ R ² NH containing solution b) holding the solution obtained from step a) at temperatures of 5 to 50 ⁰ C for a time in the range of 10 to 120 min. c) subsequent removal of the solvent, d) heating the product obtained from step c) to temperatures in the range from 100 to 250 ^° C. and e) distillation at a pressure in the range from 10 to 200 mbar,

where the radicals R ¹ and R ^{2 of} the dialkylamine used are independently selected from the group of methyl, ethyl, n- and iso-propyl.

2. The method of claim 1, wherein R ¹ and R ^{2 are} identical.

3. The method according to any one of claims 1 to 3, wherein R ¹ and R ^{2 are} methyl.

4. The method according to any one of claims 1 to 3, wherein the lactic acid and the dialkylamine of the general formula R ¹ R ² NH are dissolved in the same solvent.

5. The method according to any one of claims 1 to 4, wherein water is used as the solvent in step a).

6. The method according to any one of claims 1 to 5, wherein the solvent is removed in step c) by applying a vacuum.

A process according to any one of claims 1 to 6, wherein the lactic acid in the lactic acid-containing solution is more pure enantionmeren.