WO2010108814A1

WO2010108814A1 - Method for producing n,n`-lactic acid dialkylamide under pressure

Info

Publication number: WO2010108814A1
Application number: PCT/EP2010/053340
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 dialkylamide from lactic acid and dialkylamine under pressure.

Description

Process for the preparation of N, l \-lactic acid dialkylamide under pressure

description

The invention relates to a process for the preparation of N, N-lactic acid dialkylamide starting from lactic acid and dialkylamine under pressure.

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 WP Ratchford et al. in JACS 1947, 69, 1911-1914, giving an 86% yield at room temperature and a reaction time of 24 hours.

In the prior art, there are a number of examples in which lactic acid dimethylamide is prepared starting from lactic acid in a multi-stage 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 preparation methods is carried out in such a way that the hydroxyl group of the lactic acid is first esterified, the carboxylic acid group is then activated by preparation of the chloride or of 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 multistage processes is that first functional groups are introduced into the molecule, which are cleaved 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 while using no other solvent except water. A further task is to obtain a high proportion of the chiral center in the reaction of enantionmeren pure lactic acids (about 90% ee).

This object is achieved by a process for preparing N, N ^'- lactic acid dialkylamide comprising the steps of

a) reacting a lactic acid-containing aqueous solution with R ¹ R ² NH in an amount of 1 to 10 equivalents based on the lactic acid used for a time in the range of 30 minutes to 24 hours under a pressure in the range of 5 to 200 bar and a temperature in the range of 50 to 300 ⁰ C, b) subsequent cooling of the reaction mixture within a time <2 STUN the to a temperature <50 ⁰ C at constant pressure of step a) c) and then removing the excess amine and water,

wherein R ¹ and R ^{2 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 in step a) 5 to 10 equivalents of R ¹ R ² NH are used, based on the lactic acid used.

The process according to the invention is advantageous if step a) has a time in the range from 0.5 to 5 hours and a pressure in the range from 100 to 150 bar and a temperature in the range from 200 to 300 ^° C. and step b) during a time <2 hours to a temperature <50 ⁰ C and a pressure in the range of 100 to 150 bar is performed

This lactic acid-containing aqueous solution is then reacted with R ¹ R ² NH, 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 is reacted with an equivalent excess of R ¹ R ² NH based on the amount of lactic acid used. Preference is given to amounts of 1 to 10 equivalents of R ¹ R ² NH, more preferably 5 to 10 equivalents of R ¹ R ² NH are used based on the lactic acid. Very particularly preferred are 8 to 10 equivalents of R ¹ R ² NH based on the lactic acid.

The reaction of lactic acid with the dialkylamine is carried out under pressure, elevated temperature and only for a short period of time. The pressures are preferably in the range from 100 to 200 bar, more preferably in the range from 130 to 150 bar. The temperature is in the range of 200 to 300 ° C, preferably in the range 240 to 260 ⁰ C. The reaction is preferably carried out for a time in the range of 0.5 to 5 hours in the range of 0.5 to 1, 5 hours.

For the production of N, N ^'- Milchsäuredimethylamid is the time for the step a) ranges from 0.5 to 5 hours, particularly preferably in the range of 0.5 to 1, 5

Hours. In this case, the reactor is brought to a temperature in the range of 200 to 300 ° C, preferably in the range of 240 ° C to 260 ⁰ C. During step a) of the process according to the invention, the pressure in the autoclave is in the range from 100 to 150 bar, more preferably in the range from 130 to 150 bar. The process according to the invention can be prepared in any metal autoclave known to the person skilled in the art. Preference is given to metal autoclaves of high-alloy stainless steel or nickel-based alloys.

Both L- and D-lactic acid can be used for the process according to the invention, as well as a racemic mixture of these two lactic acids. Starting from the pure enantiomers, the chiral center remains> 90% during the process of the invention. Starting from the racemic mixture obtained according to the novel process according to the ratio in the racemic mixture and the same mixing ratio of D and LN, N ^' -Milch- Säuredialkylamids.

In step c) of the process according to the invention, the desired end product is separated from excess water. This separation can be carried out by the methods known to the person skilled in the art. These include distillation and removal of the water by applying a vacuum.

Examples

In a 300 mL metal autoclave, 22.6 g (0.22 mol) of (L) -lactic acid (88% in

Water) submitted. 96 g (2.13 mol) of dimethylamine were pressed in and a pressure of about 110 bar was obtained. The reaction mixture was heated to 250 ^° C. in the course of 2 hours and immediately cooled again (within 1 hour). The pressure was 124 bar.

The reaction was concentrated in vacuo (80 ⁰ C, 11 mbar). LN, N ^'-Milch- oic acid dimethylamide was obtained in a yield of 79% and a purity of 94% was obtained (ee 90%).

Table 1 :

Variation of reaction conditions (determination of purity by GC analysis).

^* Reaction mixture was heated to 250 ⁰ C within ² h

Claims

claims

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

a) reacting a lactic acid-containing aqueous solution with R ¹ R ² NH in an amount of 1 to 10 equivalents based on the lactic acid used for a time in the range of 30 minutes to 24 hours under a pressure in the range of 5 to 200 bar and a Temperature in the range from 50 to 300 ^° C.,

b) subsequent cooling of the reaction mixture within a time of <2 hours to a temperature <50 ⁰ C at the same pressure according to step a)

c) and then removing the excess amine and the water,

wherein R ¹ and R ^{2 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 2, wherein R ¹ and R ^{2 are} methyl.

4. The method according to any one of claims 1 to 3, wherein in step a) 5 to 10 equivalents of R ¹ R ² NH are used based on the lactic acid

5. The method of claim 4, wherein step a) during a time in the range of 0.5 to 5 hours and a pressure in the range of 100 to 150 bar and a

Temperature in the range of 200 to 300 ⁰ C and step b) is carried out for a time <2 hours and a temperature of <50 ° C at a constant pressure.