EP2274275A1

EP2274275A1 - Continuous method for producing amides of aliphatic hydroxy carboxylic acids

Info

Publication number: EP2274275A1
Application number: EP09728707A
Authority: EP
Inventors: Matthias Krull; Roman MORSCHHÄUSER; Joachim Hess; Robert Milbradt; Franz-Xaver Scherl; Andreas Wacker; Michael Seebach; Jörg APPEL
Original assignee: Clariant Finance BVI Ltd
Current assignee: Clariant Finance BVI Ltd
Priority date: 2008-04-04
Filing date: 2009-03-18
Publication date: 2011-01-19
Also published as: EP2796445A1; US20110083957A1; EA018156B9; CN101910115A; EA201001110A1; CA2720347A1; DE102008017213B4; BRPI0907149A2; MX2010010761A; DE102008017213A1; WO2009121489A1; AU2009231124A1; EA018156B1; CN101910115B; KR20100135227A

Abstract

The invention relates to a continuous method for producing hydroxycarboxylic acid amides, according to which at least one hydroxycarboxylic acid of formula (I) HO-R³-COOH (I), wherein R³ is an optionally substituted aliphatic hydrocarbon group comprising between 1 and 100 carbon atoms, is reacted with at least one amine of formula (Il) HNR¹R² (II), wherein R¹ and R²are independently hydrogen or a carbon group comprising between 1 and 100 C atoms, to form an ammonium salt, and said ammonium salt is then reacted to form a hydroxycarboxylic acid amide, under microwave irradiation in a reaction pipe, the longitudinal axis of the pipe being oriented in the direction of propagation of the microwaves of a monomode microwave applicator.

Description

description

Continuous process for the preparation of amides of aliphatic hydroxycarboxylic acids

Amides of aliphatic hydroxycarboxylic acids are very interesting as chemical raw materials. Amides derived from lower hydroxycarboxylic acids are liquids with very high dissolving power, and especially tertiary amides have excellent properties as aprotic, polar solvents. In particular tertiary amides of chiral Hyrdoxycarbonsäuren are useful as aids in the separation of enantiomers. Amides of longer-chain hydroxycarboxylic acids have interesting properties as surface-active substances.

In the industrial production, a reactive derivative of a hydroxycarboxylic acid such as acid anhydride, acid chloride or ester is usually reacted with an amine. On the one hand, this leads to high production costs and, on the other hand, to undesired accompanying products, such as, for example, salts or acids, which have to be separated off and disposed of or worked up. Thus, for example, in the Schotten-Baumann synthesis, after which numerous hydroxycarboxylic acid amides are produced industrially, equimolar amounts of common salt are formed. The desirable direct thermal condensation of carboxylic acids and amines requires very high temperatures and long reaction times, but only moderate yields are obtained (J. Am. Chem. Soc., 59 (1937), 401-402). Furthermore, the separation of acid used and amide formed is often extremely expensive, since both often have very similar boiling points and also form azeotropes.

GB-414 366 discloses a process for the preparation of substituted amides by thermal condensation. In the examples, higher-boiling carboxylic acids are reacted with gaseous secondary amines at temperatures of 200-250 ^° C. The crude products are purified by distillation or bleaching. Particularly problematic in these preparation processes are very long reaction times to achieve a commercially interesting conversion and the corrosivity of the reaction mixtures of acid, amine, amide and water of reaction, which strongly attack or dissolve metallic reaction vessels at the required high reaction temperatures. The metal contents thus introduced into the products are very undesirable because they not only affect the product properties in terms of their color but also catalyze decomposition reactions and thus reduce the yield. The latter problem can be avoided in part by special reaction vessels made of highly corrosion-resistant materials or with corresponding coatings, which nevertheless requires long reaction times and thus leads to products impaired in their color. As unwanted side reactions are, for example, an oxidation of the amine, a thermal disproportionation of secondary amines to primary and tertiary amine and a decarboxylation of the carboxylic acid mentioned. Further, in thermal condensations of hydroxycarboxylic acids with amines, elimination of the hydroxyl group to form olefins, aminolysis of the hydroxyl group to form amide amines as well as esterifications to form oligomers and polymers are observed as side reactions. All of these side reactions reduce the yield of the target product.

A recent approach to the synthesis of amides is the microwave assisted conversion of carboxylic acids and amines to amides.

Vazquez-Tato, Synlett, 1993, 506, discloses the use of microwaves as a heat source for the preparation of amides from carboxylic acids and arylaliphatic amines via the ammonium salts. The syntheses were carried out on a 10 mmol scale.

Gelens et al., Tetrahedron Letters 2005, 46 (21), 3751-3754, discloses a

Variety of amides, which were synthesized with the aid of microwave radiation, but no hydroxycarboxylic acid amides. Syntheses were done in 10 ml tubes. Massicot et al., Synthesis 2001, No. 16, pp. 2441-2444 discloses the synthesis of tartramides under the influence of microwaves, highlighting economic considerations and safety and environmental benefits for the use of microwaves; However, the reactions are carried out only on a mmol scale. Reactions with secondary amines could not be observed.

The scale-up of such microwave-assisted reactions from the laboratory to an industrial scale and thus the development of plants capable of producing several tons, such as several tens, hundreds or thousands of tons per year, with space-time Yields are suitable, but so far could not be realized. The reason for this is, on the one hand, the limited penetration depth of microwaves into the reaction mixture, which is usually limited to a few millimeters to a few centimeters, which limits reactions, especially in batch processes, to small vessels or leads to very long reaction times in stirred reactors. A desirable for the irradiation of large quantities of substances with microwaves increase the field strength are set narrow limits in particular in the previously preferred for scale-up of chemical reactions used multimode devices by then occurring discharge processes and plasma formation. Furthermore, the inhomogeneity of the microwave field caused by localized overheating of the reaction mixture, caused by more or less uncontrolled reflections of the microwaves irradiated into the microwave oven on the walls thereof and the reaction mixture in the commonly used multimode microwaves causes problems in scale-up. In addition, the microwave absorption coefficient of the reaction mixture, which often changes during the reaction, presents difficulties with regard to a reliable and reproducible reaction.

C. Chen et al., J. Chem. Soc., Chem. Commun., 1990, 807-809, describe a continuous laboratory microwave reactor in which the reaction mixture by a mounted in a microwave oven Teflon coil is guided. A similar continuous laboratory microwave reactor is described by Cablewski et al., J. Org. Chem. 1994, 59, 3408-3412 for conducting a variety of chemical reactions. In both cases, however, the multimode microwave does not allow upscaling in the large scale. you

Microwave absorption efficiency of the reaction product is low due to the microwave energy more or less homogeneously distributed in the applicator space in multimode microwave applicators and not focused on the coil. A strong increase in the radiated microwave power leads here to unwanted plasma discharges. Furthermore, the time-varying spatial inhomogeneities of the microwave field, referred to as hot spots, make reliable and reproducible reaction on a large scale impossible.

Furthermore, single-mode or single-mode microwave applicators are known in which a single wave mode is used, which propagates in only one spatial direction and is focused by precisely dimensioned waveguides on the reaction vessel. Although these devices allow higher local field strengths, but so far due to the geometric requirements (eg, the intensity of the electric field at its wave crests is greatest and goes to the nodes to zero) so far on small reaction volumes (<50 ml) Laboratory scale limited.

Therefore, a process has been sought for the preparation of hydroxycarboxylic acid amides in which hydroxycarboxylic acid and amine can also be converted to the amide on an industrial scale under microwave irradiation. Of particular interest was tertiary amides of hydroxycarboxylic acids. The aim is to achieve as high as possible, that is to say quantitative conversion rates and yields. The method should further enable a possible energy-saving production of carboxylic acid amides, that is, the microwave power used should be as quantitatively absorbed by the reaction mixture and thus offer the process a high energy efficiency. There should be no or only subordinate Amounts of by-products are incurred. The amides should also have the lowest possible metal content and a low intrinsic color. In addition, the process should ensure a safe and reproducible reaction.

Surprisingly, it was found that amides of

Hydroxycarboxylic acids by direct reaction of hydroxycarboxylic acids with amines in a continuous process by only brief heating by irradiation with microwaves in a reaction tube, the longitudinal axis is in the propagation direction of the microwaves of a single-mode microwave applicator can produce in technically relevant quantities. In this case, the microwave energy radiated into the microwave applicator is absorbed virtually quantitatively by the reaction mixture. The inventive method also has a high level of safety in the implementation and provides a high reproducibility of the set reaction conditions. The amides prepared by the process according to the invention show a high purity and low intrinsic coloration, which are not accessible without additional process steps, compared to conventional preparation processes.

The invention relates to a continuous process for the preparation of hydroxycarboxylic acid amides by reacting at least one hydroxycarboxylic acid of the formula I

HO-R ³ -COOH (I)

wherein R ^{3 is} an optionally substituted aliphatic hydrocarbon radical having 1 to 100 carbon atoms, with at least one amine of the formula II

HNR ¹ R ² (II)

wherein R ¹ and R ² independently of one another represent hydrogen or a hydrocarbon radical having 1 to 100 C atoms, is reacted to an ammonium salt and this ammonium salt is subsequently reacted under microwave irradiation in a reaction tube whose longitudinal axis is in the direction of propagation of the microwaves of a single-mode microwave applicator to Hydroxycarbonsäureamid.

Suitable hydroxycarboxylic acids of the formula I are generally compounds which have at least one carboxyl group and at least one hydroxyl group on an aliphatic hydrocarbon radical R ³ . Thus, the process of the invention is also suitable for the amidation of hydroxypolycarboxylic acids with, for example, two, three, four or more carboxyl groups. In the

Reaction of polycarboxylic acids with ammonia or primary amines according to the process of the invention can also give imides. Likewise, the process according to the invention is suitable for the amidation of polyhydroxycarboxylic acids with, for example, two, three, four or more hydroxyl groups, although the hydroxycarboxylic acids may only carry one hydroxyl group per carbon atom of the aliphatic hydrocarbon radical R ³ . Particularly preferred are hydroxycarboxylic acids which carry an aliphatic hydrocarbon radical R ³ having 1 to 30 C atoms and in particular having 2 to 24 C atoms, for example having 3 to 20 C atoms. The hydrocarbon radical R ³ may also contain heteroatoms such as, for example, oxygen, nitrogen, phosphorus and / or sulfur, but preferably not more than one heteroatom per 3 C atoms. The hydroxycarboxylic acids of formula I may be of natural or synthetic origin.

The aliphatic hydrocarbon radicals R ³ can be linear, branched or cyclic. The carboxyl group may be bonded to a primary, secondary or tertiary C atom. It is preferably bound to a primary carbon atom. The hydroxyl group may be bonded to a primary, secondary or tertiary carbon atom. Particularly advantageous is the process for the amidation of hydroxycarboxylic acids containing a hydroxyl group bonded to a secondary carbon atom and especially for the amidation of those hydroxycarboxylic acids in which the hydroxyl group is in the α-position to the carboxyl group. Carboxyl and hydroxyl group can be attached to the same or different C atoms of R ^{3 may be} bonded. The hydrocarbon radicals R ³ may be saturated or unsaturated. Unsaturated hydrocarbon radicals R ³ contain one or more and preferably one, two or three C =C double bonds. Preferably, there is no double bond in α, ß-position to the carboxyl group. Preferred cyclic aliphatic

Hydrocarbon radicals have at least one ring with four, five, six, seven, eight or more ring atoms. The hydrocarbon radical R ³ may carry one or more, for example two, three, four or more further substituents. Such substituents can be, for example, halogen atoms, halogenated alkyl radicals, C 1 -C 8 -alkoxy, such as, for example, methoxy, poly (C 1 -C ₅ -alkoxy) -,

Poly (C 1 -C ₅ -alkoxy) alkyl, carboxyl, hydroxyl, ester, amide, cyano, nitrile, nitro and / or aryl groups having from 5 to 20 carbon atoms, such as phenyl groups, with the proviso the substituents are stable under the reaction conditions and do not undergo side reactions such as elimination reactions. The C ₅ -C ₂ o-aryl groups may in turn carry substituents. Such substituents can include, for example, halogen atoms, halogenated alkyl radicals, CrC ₂ o-alkyl, C ₂ -C ₂ o-alkenyl, C ₁ -C ₅ -AIkOXy- such as methoxy, ester, amide, hydroxy, cyano -, nitrile, and / or nitro groups. However, the alkyl radical carries at most as many substituents as it has valencies.

The process according to the invention is particularly advantageously proven for the preparation of amides and in particular for the preparation of tertiary amides of lower hydroxymonocarboxylic acids with aliphatic C 1 -C ₄ -hydrocarbon radicals. Also particularly advantageous is the process for the preparation of hydroxypolycarboxylic acids having a total of 3 to 6 carbon atoms (including the carboxyl carbon atoms) and 1 or 2 hydroxyl groups.

Suitable aliphatic hydroxycarboxylic acids are, for example, hydroxyacetic acid, 2-hydroxypropionic acid, 3-hydroxypropionic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-hydroxybutyric acid, 2-hydroxy-2-methylpropionic acid, 4-hydroxypentanoic acid, 5-hydroxypentanoic acid, 2,2-dimethyl-3 hydroxypropionic acid, 5-hydroxyhexanoic acid, 2-hydroxyoctanoic acid, 2-hydroxytetradecanoic acid, 15-hydroxypentadecanoic acid, 16-hydroxyhexadecanoic acid, 12-hydroxystearic acid (ricinoleic acid) and α-hydroxyphenylacetic acid (mandelic acid), 4-hydroxymandelic acid, 2-hydroxy-2-phenylpropionic acid, and 3-hydroxy-3-phenylpropionic acid , Also hydroxypolycarboxylic acids such as malic acid,

Citric acid and isocitric acid, polyhydroxycarboxylic acids such as gluconic acid and mevalonic acid (3,5-dihydroxy-3-methylpentanoic acid) and polyhydroxypolycarboxylic acids such as tartaric acid can be converted by means of the method according to the invention into the corresponding diamides. According to the invention particularly preferred hydroxycarboxylic acids are

Hydroxyacetic acid, 2-hydroxypropionic acid, mandelic acid and ricinoleic acid.

Mixtures of different hydroxycarboxylic acids are also suitable for use in the process according to the invention.

The process according to the invention is preferably suitable for the preparation of secondary hydroxycarboxamides, ie for the reaction of hydroxycarboxylic acids with amines, in which R ^{1 is} a hydrocarbon radical having 1 to 100 carbon atoms and R ^{2 is} hydrogen.

The process according to the invention is particularly preferably suitable for the preparation of tertiary hydroxycarboxamides, ie for the reaction of hydroxycarboxylic acids with amines, in which both radicals R ¹ and R ² independently of one another are a hydrocarbon radical having 1 to 100 carbon atoms. The radicals R ¹ and R ² may be the same or different. In a particularly preferred embodiment, R ¹ and R ^{2 are the} same.

In a first preferred embodiment, R ¹ and / or R ^{2 are} independently an aliphatic radical. This preferably has 1 to 24, more preferably 2 to 18 and especially 3 to 6 C atoms. The aliphatic radical may be linear, branched or cyclic. It can still be saturated or unsaturated. The hydrocarbon radical may have substituents such as, for example, C 1 -C ₅ -alkoxy, cyano, nitrile, nitro and / or C ₅ -C ₂ 0-aryl groups such as carry phenyl radicals. The C ₅ -C ₂ o-aryl radicals may in turn optionally substituted with halogen atoms, halogenated alkyl groups, -C ₂ o alkyl, C ₂ -C ₂ o-alkenyl, C ₁ -C ₅ -AIkOXy- such as methoxy, ester , Amide, cyano, nitrile, and / or nitro groups. Particularly preferred aliphatic radicals are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl, n-hexyl, cyclohexyl, n-octyl, n-decyl, n-dodecyl, tridecyl, Isotridecyl, tetradecyl, hexadecyl, octadecyl and methylphenyl. In a particularly preferred embodiment R ¹ and / or R ² are independently hydrogen, a Ci-C ₆ alkyl, C ₂ -C ₆ -alkenyl or C ₃ -C ₆ cycloalkyl radical and especially an alkyl radical containing 1 , 2, or 3 C atoms. These radicals can carry up to three substituents.

In another preferred embodiment, R ¹ and R ² together with the nitrogen atom to which they are attached form a ring. This ring preferably has 4 or more, such as 4, 5, 6 or more ring members.

Preferred further ring members are carbon, nitrogen, oxygen and sulfur atoms. The rings in turn may carry substituents such as alkyl radicals. Suitable ring structures are, for example, morpholinyl, pyrrolidinyl, piperidinyl, imidazolyl and azepanyl radicals.

In a further preferred embodiment R ¹ and / or R ² are independently an optionally substituted C ₆ -C ₂ aryl group or an optionally substituted heteroaromatic group having 5 to 12 ring members.

In a further preferred embodiment, R ¹ and / or R ² independently of one another are an alkyl radical interrupted by heteroatoms. Particularly preferred heteroatoms are oxygen and nitrogen.

Thus, R ¹ and / or R ² independently of one another are preferably radicals of the formula III

- (R ⁴ -O) _n -R ⁵ (III) wherein

R ^{4 is} an alkylene group having 2 to 6 carbon atoms and preferably 2 to

4 C atoms, such as, for example, ethylene, propylene, butylene or mixtures thereof,

R ^{5 is} a hydrocarbon radical having 1 to 24 C atoms or NR ¹⁰ R ¹¹ , and n is a number between 2 and 50, preferably between 3 and 25 and in particular between 4 and 10 and R ¹⁰ , R ¹¹ are each independently hydrogen an aliphatic radical having 1 to 24 C atoms and preferably 2 to 18 C atoms, an aryl group or heteroaryl group having 5 to 12 ring members, a poly (oxyalkylene) group having 1 to 50 poly (oxyalkylene) units, wherein the Derive polyoxyalkylene units of alkylene oxide having 2 to 6 carbon atoms, or R ¹⁰ and R ¹ together with the

Nitrogen to which they are attached, form a ring with 4, 5, 6 or more ring members stand.

Furthermore, R ¹ and / or R ² independently of one another are preferably radicals of the formula IV

- [R ⁶ -N (R ⁷ )] _m - (R ⁷ ) (IV)

wherein R ^{6 is} an alkylene group having 2 to 6 carbon atoms, and preferably 2 to

4 C atoms such as ethylene, propylene or mixtures thereof, each R ^{7 is} independently hydrogen, an alkyl or

Hydroxyalkyl radical having up to 24 carbon atoms such as 2 to 20 carbon atoms, a polyoxyalkylene radical - (R ⁴ -O) _p -R ⁵ , or a

Polyiminoalkylene radical - [R ⁶ -N (R ⁷ )] _q - (R ⁷ ), where R ⁴ , R ⁵ , R ⁶ and R ^{7 have} the meanings given above, and q and p independently of one another represent 1 to 50, and m is a number from 1 to 20, and preferably from 2 to 10, such as three, four, five or six. The radicals of the formula IV preferably contain 1 to 50, in particular 2 to 20, nitrogen atoms.

Depending on the stoichiometric ratio between hydrocarboxylic acid (I) and

Polyamine (IV) are one or more amino groups, each carrying at least one hydrogen atom, converted into the carboxylic acid amide. In the reaction of polycarboxylic acids with polyamines of the formula IV, in particular the primary amino groups can also be converted into imides.

For the preparation according to the invention of primary amides, preference is given to using nitrogen-containing compounds which split off ammonia gas on heating instead of ammonia. Examples of such nitrogen-containing compounds are urea and formamide.

Examples of suitable amines are ammonia, methylamine, ethylamine, propylamine, butylamine, hexylamine, cyclohexylamine, octylamine, cyclooctylamine, decylamine,, 2-cyclohexylethylamine dodecylamine, tetradecylamine, hexadecylamine, octadecylamine, dimethylamine, diethylamine, ethylmethylamine, di-n-propylamine, di -iso-propylamine, dicyclohexylamine, didecylamine, didodecylamine, ditetradecylamine, dihexadecylamine, dioctadedcylamine, benzylamine, phenylethylamine, ethylenediamine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, piperidine and pyrrolidine and mixtures thereof. Of these, dimethylamine, diethylamine, di-n-propylamine, di-iso-propylamine and ethylmethylamine are particularly preferred.

The process is particularly suitable for preparing N-methylglycolic acid amide, N-ethylmandic acid amide, N, N-dimethylglycolic acid amide, N, N-dimethylmilactic acid amide, and N, N-dimethylricinoleic acid amide.

In the process according to the invention, the hydroxycarboxylic acid is preferably used with at least equimolar amounts of amine and more preferably with one Excess amine reacted, that is, the molar ratios of amino groups to carboxyl groups are at least 1: 1 and are preferably between 100: 1 and 1, 001: 1, more preferably between 10: 1 and 1, 01: 1 such as between 5: 1 and 1, 1: 1. The carboxyl groups are virtually quantitatively converted to the amide without causing the aminolysis of hydroxyl groups. This method is particularly advantageous when the amine used is volatile. Volatile here means that the amine has a boiling point at atmospheric pressure of preferably below 200 ⁰ C such as below 160 ⁰ C and thus can be separated by distillation from the amide. In a specific embodiment, carboxylic acid and amine are used equimolar.

The preparation of the amides according to the invention is carried out by reacting carboxylic acid and amine to form the ammonium salt and subsequently irradiating the salt with microwaves in a reaction tube whose longitudinal axis is in the direction of propagation of the microwaves in a single-mode microwave applicator.

The irradiation of the salt with microwaves preferably takes place in a largely microwave-transparent reaction tube, which is located within a waveguide connected to a microwave generator. Preferably, the reaction tube is aligned axially with the central axis of symmetry of the waveguide.

The waveguide acting as a microwave applicator is preferably formed as a cavity resonator. Further preferably, the microwaves not absorbed in the waveguide are reflected at its end. By shaping the microwave applicator as a reflection-type resonator, a local increase in the electric field strength is achieved by interference with the same power supplied by the generator and increased energy utilization.

The cavity resonator is preferably operated in mode _n E i _0, where n is an integer and represents the number of field maxima of the microwave along the central axis of symmetry of the resonator. This is the case with this operation directed electrical field in the direction of the central axis of symmetry of the cavity. It has a maximum in the area of the central axis of symmetry and decreases to the lateral surface to the value zero. This field configuration is rotationally symmetric about the central axis of symmetry. Depending on the desired flow rate of the reaction mixture through the reaction tube, the required temperature and the required residence time in the resonator, the length of the resonator is selected relative to the wavelength of the microwave radiation used. N is preferably an integer from 1 to 200, particularly preferably from 2 to 100, in particular from 4 to 50 and especially from 3 to 20, for example 3, 4, 5, 6, 7 or 8.

The irradiation of the microwave energy into the waveguide acting as a microwave applicator can take place via suitably dimensioned holes or slots. In a particularly preferred embodiment of the invention, the irradiation of the ammonium salt with microwaves in a reaction tube, which is located in a waveguide with coaxial transition of the microwaves. For this method, particularly preferred microwave devices are constructed of a cavity resonator, a coupling device for coupling a microwave field in the cavity and each with an opening at two opposite end walls for passing the reaction tube through the resonator. The coupling of the microwaves in the cavity resonator is preferably carried out via a coupling pin, which projects into the cavity resonator. The coupling pin is preferably shaped as a preferably metallic inner conductor tube functioning as a coupling antenna. In a particularly preferred embodiment of this coupling pin protrudes through one of the frontal openings into the cavity resonator. Particularly preferably, the reaction tube connects to the inner conductor tube of the coaxial transition and in particular it is guided through its cavity into the cavity resonator. Preferably, the reaction tube is aligned axially with a central axis of symmetry of the cavity resonator, for which purpose the cavity resonator preferably each has a central opening on two opposite end walls for passing the reaction tube. The feeding of the microwaves in the coupling pin or in the acting as a coupling antenna inner conductor tube can be done for example by means of a coaxial connecting cable. In a preferred embodiment, the microwave field is supplied to the resonator via a waveguide, wherein the protruding from the cavity resonator end of the coupling pin is guided into an opening which is located in the wall of the waveguide in the waveguide and the waveguide takes microwave energy and in the Resonator couples.

In a specific embodiment, the irradiation of the salt with microwaves is carried out in a microwave-transparent reaction tube which is axially symmetrical in an E ₀ i _n circular waveguide with coaxial transition of the microwaves. In this case, the reaction tube is guided through the cavity of an inner conductor tube acting as a coupling antenna into the cavity resonator. In a further preferred embodiment, the microwave is irradiated with microwaves in a microwave-transparent reaction tube which is passed through an eoin cavity resonator with axial feeding of the microwaves, wherein the length of the cavity is dimensioned such that n = 2 or more field maxima of the microwave form. In a further preferred embodiment, the irradiation of the salt with microwaves in a microwave-transparent reaction tube, which is axially symmetrical in a circular cylindrical Eoi _n- cavity resonator with coaxial transition of the microwaves, wherein the length of the cavity is dimensioned so that n = 2 or more Form field maxima of the microwave.

Microwave generators, such as the magnetron, the klystron and the gyrotron are known in the art.

The used for carrying out the method according to the invention

Reaction tubes are preferably made of largely microwave-transparent, high-melting material. Non-metallic reaction tubes are particularly preferably used. Under largely microwave transparent are here Materials understood that absorb as little microwave energy and convert it into heat. As a measure of the ability of a substance to absorb microwave energy and to convert it into heat, the dielectric loss factor tan δ = ε ^' Vε ^{' is} often used. The dielectric loss factor tan δ is defined as the ratio of dielectric loss ε ^" and

Dielectric constant ε ^' . Examples of tan δ values of various materials are given, for example, in D. Bogdal, Microwave Assisted Organic Synthesis, Elsevier 2005. For reaction tubes which are suitable according to the invention, materials having tan δ values measured at 2.45 GHz and 25 ^° C. of less than 0.01, in particular less than 0.005 and especially less than 0.001 are preferred. As a preferred microwave-transparent and temperature-stable materials are primarily materials based on minerals such as quartz, alumina, zirconia and the like into consideration. Also thermally stable plastics such as in particular fluoropolymers such as Teflon, and engineering plastics such as polypropylene, or polyaryletherketones such as glass fiber reinforced polyetheretherketone (PEEK) are suitable as pipe materials. In order to withstand the temperature conditions during the reaction, in particular minerals coated with these plastics, such as quartz or aluminum oxide, have proven to be suitable as reactor materials.

For the process according to the invention particularly suitable reaction tubes have an inner diameter of one millimeter to about 50 cm, especially between 2 mm and 35 cm, for example between 5 mm and 15 cm. Reaction tubes are understood here to be vessels whose ratio of length to diameter is greater than 5, preferably between 10 and 100,000, particularly preferably between 20 and 10,000, for example between 30 and 1,000. The length of the reaction tube is understood here as the distance of the reaction tube on which the microwave irradiation takes place. In the reaction tube baffles and / or other mixing elements can be installed.

For the method according to the invention, particularly suitable Eor cavity resonators preferably have a diameter which corresponds to at least half the wavelength of the microwave radiation used. The diameter of the cavity resonator is preferably from 1.0 to 10 times, more preferably from 1.1 to 5 times and in particular from 2.1 to 2.6 times the half wavelength of the microwave radiation used. Preferably, the E ₀ i cavity resonator has a round cross-section, which is also referred to as Eoi round waveguide. Particularly preferably it has a cylindrical shape and especially a circular cylindrical shape.

The reaction tube is usually provided at the inlet with a metering pump and a pressure gauge and at the outlet with a pressure holding device and a heat exchanger. This allows reactions in a very wide range of pressure and temperature.

The reaction of amine and carboxylic acid to form the ammonium salt can be carried out continuously, batchwise or else in semi-batch processes. Thus, the preparation of the ammonium salt can be carried out in an upstream (semi) -batch process, such as in a stirred tank. The ammonium salt is preferably generated in situ and not isolated. In a preferred embodiment, the educts amine and carboxylic acid, both independently of one another optionally diluted with solvent, are mixed shortly before they enter the reaction tube. Thus, it has proven particularly useful to carry out the reaction of amine and carboxylic acid to form the ammonium salt in a mixing section, from which the ammonium salt, optionally after intermediate cooling, is conveyed into the reaction tube. With further preference the educts are fed to the process according to the invention in liquid form. For this purpose, higher-melting and / or higher-viscosity starting materials, for example in the molten state and / or with solvent, for example, can be used as solution, dispersion or emulsion. If used, a catalyst can be added to one of the educts or else to the educt mixture before it enters the reaction tube. Solid, pulverulent and heterogeneous systems can also be reacted by the process according to the invention, with only corresponding technical devices for conveying the reaction mixture being required. The ammonium salt can be fed into the reaction tube either at the end guided through the inner conductor tube, or at the opposite end.

By varying the tube cross-section, length of the irradiation zone (this is understood to mean the distance of the reaction tube in which the reaction mixture is exposed to microwave radiation), flow rate, geometry of the cavity, the irradiated microwave power and the temperature reached thereby, the reaction conditions are adjusted so that the maximum reaction temperature is reached as quickly as possible and the residence time at maximum temperature remains so short that so few side or subsequent reactions occur as possible. The reaction mixture can be passed through the reaction tube several times to complete the reaction, optionally after intermediate cooling. In many cases, it has proven useful if the reaction product immediately after leaving the reaction tube z. B. is cooled by jacket cooling or relaxation. With slower reactions, it has often proven useful to keep the reaction product after leaving the reaction tube for a certain time at the reaction temperature.

The advantages of the method according to the invention lie in a very uniform irradiation of the reaction material in the center of a symmetrical microwave field within a reaction tube whose longitudinal axis is in the propagation direction of the microwaves of a single-mode microwave applicator, and in particular within a EorHohlraumresonators example with coaxial transition. The reactor design according to the invention allows reactions to be carried out even at very high pressures and / or temperatures. By increasing the temperature and / or pressure, a clear increase in the degree of conversion and yield is also observed in comparison to known microwave reactors, without causing undesired side reactions and / or discoloration. Surprisingly, a very high efficiency in the utilization of the radiated microwave energy in the cavity resonator is achieved, which is usually over 50%, often over 80%, sometimes over 90% and 1 o

in special cases more than 95%, such as over 98% of the radiated microwave power, and thus offers economic as well as ecological advantages over conventional manufacturing methods as well as compared to microwave methods of the prior art.

The inventive method also allows a controlled, safe and reproducible reaction. Since the reaction mixture is moved in the reaction tube parallel to the propagation direction of the microwaves, known overheating phenomena are compensated by uncontrollable field distributions, which lead to local overheating by changing intensities of the field, for example in wave crests and nodes, by the flow of the reaction material. The advantages mentioned also make it possible to work with high microwave powers of, for example, more than 10 kW or more than 100 kW and, thus, in combination with a short residence time in the cavity resonator, achieve large production quantities of 100 and more tons per year in one system.

It was particularly surprising that despite the very short residence time of the ammonium salt in the microwave field in the continuously flowing flow tube, a very extensive amidation with conversions of generally more than 80%, often even more than 90%, for example over 95% based on the used in the deficit Component takes place without formation of appreciable amounts of by-products. Despite the presence of OH groups having an alcoholic character in the acid structures according to the invention, these are attacked neither by the acid component itself (ester formation) nor by the amine function (aminolysis). Thus, neither esters nor polyesters could be found as by-products. In a corresponding implementation of these ammonium salts in a flow tube of the same dimensions under thermal jacket heating to achieve appropriate

Required reaction temperatures extremely high wall temperatures, which led to the formation of colored species, but cause the same time interval only minor amide formation. Furthermore, those according to the invention Process produced products very low metal contents without the need for further processing of the crude products. Thus, the metal contents of the products produced by the process according to the invention based on iron as the main element are usually below 25 ppm, preferably below 15 ppm, especially below 10 ppm, such as between 0.01 and 5 ppm iron.

Preferably, the temperature rise caused by the microwave irradiation is limited to a maximum of 500 ^° C., for example by controlling the microwave intensity, the flow rate and / or by cooling the reaction tube, for example by a stream of nitrogen. Has proven particularly suitable to carry out the reaction at temperatures between 150 and a maximum of 400 ° C and in particular between 180 and a maximum of 350 ⁰ C and in particular 200-320 ⁰ C, for example at temperatures of 220-300 ⁰ C.

The duration of the microwave irradiation depends on various factors such as the geometry of the reaction tube, the radiated microwave energy, the specific reaction and the desired degree of conversion. Usually, the microwave irradiation is carried out for a period of less than 30 minutes, preferably between 0.01 second and 15 minutes, more preferably between 0.1 second and 10 minutes and in particular between one second and 5 minutes, for example between 5 seconds and 2 minutes , The intensity (power) of the microwave radiation is adjusted so that the reaction material when leaving the cavity resonator has the desired maximum temperature. In a preferred embodiment, the reaction product is cooled as quickly as possible directly after completion of the microwave irradiation to temperatures below 120 ⁰ C ₁ below 100 ⁰ C and especially below 60 ⁰ C.

The reaction is preferably carried out at pressures between 0.01 and 500 bar and more preferably between 1 bar (atmospheric pressure) and 150 bar and specifically carried out between 1, 5 bar and 100 bar such as between 3 bar and 50 bar. Working under elevated pressure has proven particularly useful, the starting materials or products, the optionally present solvent and / or above the reaction water formed during the reaction being worked above the boiling point (at atmospheric pressure). More preferably, the pressure is set so high that the reaction mixture remains in the liquid state during microwave irradiation and does not boil.

To avoid side reactions and to produce as pure as possible products, it has been proven to handle starting materials and products in the presence of an inert protective gas such as nitrogen, argon or helium.

In a preferred embodiment, to accelerate or complete the reaction in the presence of dehydrating

Catalysts worked. Preferably, one works in the presence of an acidic inorganic, organometallic or organic catalyst or mixtures of several of these catalysts.

Examples of acidic inorganic catalysts for the purposes of the present invention are sulfuric acid, phosphoric acid, phosphonic acid, hypophosphorous acid, aluminum sulfate hydrate, alum, acidic silica gel and acidic aluminum hydroxide. Furthermore, for example, aluminum compounds of the general formula AI (OR ¹⁵ ) ₃ and titanates of the general formula Ti (OR ¹⁵ ) ₄ can be used as acidic inorganic catalysts, wherein the radicals R ^{15 may be} the same or different and are independently selected from Ci-Cio Alkyl radicals, for example methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, sec-pentyl, neo-pentyl , 1, 2-dimethylpropyl, iso-amyl, n-hexyl, sec-hexyl, n-heptyl, n-octyl, 2-Ethylhexy, n-nonyl or n-decyl, _{_C3-Ci2} cycloalkyl, for example cyclopropyl , Cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl and cyclododecyl; preferred are cyclopentyl, cyclohexyl and cycloheptyl. Preferably, the radicals R ¹⁵ in Al (OR ¹⁵ ) ₃ or Ti (OR ¹⁵ J _{4 in} each case the same and selected from isopropyl, butyl and 2-ethylhexyl.

Preferred acidic organometallic catalysts are, for example, selected from dialkyltin oxides (R ¹⁵ ^ SnO, where R ¹⁵ is defined standing as above A particularly preferred representatives of acidic organometallic catalysts is di-n-butyltin oxide, which as a so-called Oxo-tin or as Fascat ^®. - Brands is commercially available.

Preferred acidic organic catalysts are acidic organic compounds with, for example, phosphate groups, sulfonic acid groups, sulfate groups or phosphonic acid groups. Particularly preferred sulfonic acids contain at least one sulfonic acid group and at least one saturated or unsaturated, linear, branched and / or cyclic hydrocarbon radical having 1 to 40 carbon atoms and preferably having 3 to 24 carbon atoms. Particular preference is given to aromatic sulfonic acids, especially alkylaromatic monosulfonic acids having one or more C ₁ -C ₂₈ -alkyl radicals and, in particular, those having C ₃ -C ₂₂ -alkyl radicals. Suitable examples are methanesulfonic acid, butanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, xylenesulfonic acid, 2-mesitylenesulfonic acid, 4-ethylbenzenesulfonic acid, isopropylbenzenesulfonic acid, 4-butylbenzenesulfonic acid, 4-octylbenzenesulfonic acid; Dodecylbenzenesulfonic acid, didodecylbenzenesulfonic acid, naphthalenesulfonic acid. Acidic ion exchangers can also be used as acidic organic catalysts, for example poly (styrene) sulfonic acid groups which are crosslinked with about 2 mol% of divinylbenzene.

Boron acid, phosphoric acid, polyphosphoric acid and polystyrenesulfonic acids are particularly preferred for carrying out the process according to the invention. Especially preferred are titanates of the general formula Ti (OR ¹⁵ ) ₄ and especially titanium tetrabutylate and titanium tetraisopropylate.

If it is desired to use acidic inorganic, organometallic or organic catalysts, according to the invention 0.01 to 10% by weight, preferably 0.02 to 2 wt .-% catalyst. In a particularly preferred embodiment, working without a catalyst.

In a further preferred embodiment, the microwave irradiation is carried out in the presence of acidic solid catalysts. In this case, the solid catalyst is suspended in the optionally mixed with solvent ammonium salt or advantageously the optionally with solvent-added ammonium salt passed through a fixed bed catalyst and exposed to microwave radiation. Examples of suitable solid catalysts are zeolites, silica gel, montmorillonite and (partially) crosslinked polystyrenesulphonic acid, which may optionally be impregnated with catalytically active metal salts. Suitable acidic ion exchanger based on polystyrene sulfonic acids that can be used as solid phase catalysts are for example available from the company Rohm & Haas under the trademark Amberlyst ^®.

It has been proven to work in the presence of solvents to lower, for example, the viscosity of the reaction medium and / or to fluidize the reaction mixture, if it is heterogeneous. In principle, all solvents can be used which are inert under the reaction conditions used and do not react with the starting materials or the products formed. An important factor in the selection of suitable solvents is their polarity, which on the one hand determines the dissolving properties and on the other hand determines the extent of the interaction with microwave radiation. A particularly important factor in the selection of suitable solvents is their dielectric loss ε. "The dielectric loss ε" describes the proportion of

Microwave radiation which is converted into heat during the interaction of a substance with microwave radiation. The latter value has proved to be a particularly important criterion for the suitability of a solvent for carrying out the method according to the invention. Working in solvents, which has the lowest possible degree of effectiveness, has proven particularly useful

Show microwave absorption and thus provide only a small contribution to the heating of the reaction system. Preferred solvents for the process according to the invention have a measured at room temperature and 2450 MHz dielectric loss ε "of less than 10 and preferably less than 1 such as less than 0.5 An overview of the dielectric loss of various solvents can be found, for example, in" Microwave Synthesis "by BL Hayes, CEM Publishing 2002. For the method according to the invention in particular solvents with ε "values below 10 are suitable

N-methylpyrrolidone, N, N-dimethylformamide or acetone, and in particular solvents having ε "values below 1. Examples of particularly preferred solvents having ε" values below 1 are aromatic and / or aliphatic hydrocarbons, such as, for example, toluene, xylene, ethylbenzene, Tetralin, hexane, cyclohexane, decane, pentadecane, decalin and commercial

Hydrocarbon mixtures such as petroleum fractions, kerosene, solvent naphtha, Shellsol ^® AB, Solvesso ^® 150, Solvesso ^® 200, Exxsol ^®, Isopar ^® and Shellsol ^® - types. Solvent mixtures which have ε "values preferably below 10 and especially below 1 are equally preferred for carrying out the process according to the invention.

In principle, the process according to the invention can also be carried out in solvents having higher ε "values of, for example, 5 and higher, in particular with ε" values of 10 and higher. However, the observed accelerated heating of the reaction mixture requires special measures to maintain the maximum temperature.

If it is carried out in the presence of solvents, their proportion of the reaction mixture is preferably between 2 and 95 wt .-%, especially between 5 and 90 wt .-% and in particular between 10 and 75 wt .-%, such as between 30 and 60 wt .-%. Particularly preferably, the reaction is carried out solvent-free.

Microwaves are electromagnetic waves having a wavelength between about 1 cm and 1 m and frequencies between about 300 MHz and 30 GHz. This frequency range is suitable in principle for the method according to the invention. For the inventive method microwave radiation is preferred with those for industrial, scientific and medical applications used shared frequencies such as at frequencies of 915 MHz, 2.45 GHz, 5.8 GHz or 27.12 GHz.

The microwave power to be radiated into the cavity resonator for carrying out the method according to the invention depends, in particular, on the geometry of the reaction tube and thus the reaction volume and the duration of the required irradiation. It is usually between 200 W and several 100 kW and in particular between 500 W and 100 kW such as between 1 kW and 70 kW. It can be generated by one or more microwave generators.

In a preferred embodiment, the reaction is carried out in a pressure-resistant inert tube, wherein the water of reaction forming and optionally starting materials and, if present, solvents lead to a pressure build-up. After completion of the reaction, the excess pressure can be used by relaxation for volatilization and separation of water of reaction, excess starting materials and, if appropriate, solvents and / or for cooling the reaction product. In a further embodiment, the water of reaction formed after cooling and / or venting by conventional methods such as phase separation, distillation stripping, flashing and / or absorption is separated.

In order to complete the reaction, it has proven useful in many cases to suspend the resulting crude product after removal of water of reaction and optionally discharge of product and / or by-product of the microwave irradiation, where appropriate, the ratio of the reactants used to supplemented or unterschüssige educts.

Usually, amides prepared via the route according to the invention are obtained in a sufficient purity for further use. For special requirements, however, they can be further purified by customary purification methods such as, for example, distillation, recrystallization, filtration or chromatographic methods. The inventive method allows a very fast, energy-saving and cost-effective production of amides of lower carboxylic acids in high yields and high purity in large quantities. Due to the very uniform irradiation of the ammonium salt in the center of the rotationally symmetric microwave field, it allows a safe, controllable and reproducible reaction. It is achieved by a very high efficiency in the utilization of the radiated microwave energy, the known manufacturing process significantly superior efficiency. This process does not generate significant amounts of by-products. Such rapid and selective reactions can not be achieved by conventional methods and were not to be expected by heating to high temperatures alone. The products produced by the process according to the invention are often so pure that no further preparation or post-processing steps are required.

Examples

The reactions of the ammonium salts under microwave irradiation were carried out in a ceramic tube (60 × 1 cm) which was axially symmetrical in a cylindrical cavity resonator (60 × 10 cm). On one of the end faces of the cavity resonator, the ceramic tube passed through the cavity of an inner conductor tube acting as a coupling antenna. The microwave field generated by a magnetron with a frequency of 2.45 GHz was coupled by means of the coupling antenna in the cavity resonator (Eo-i cavity applicator, single mode).

The microwave power was adjusted over the duration of the experiment in such a way that the desired temperature of the reaction mixture was kept constant at the end of the irradiation zone. The microwave powers mentioned in the test descriptions therefore represent the time average of the irradiated microwave power. The temperature measurement of the Reaction mixture was made directly after leaving the reaction zone (about 15 cm distance in an insulated stainless steel capillary, 0 1 cm) using PtIOO temperature sensor. Microwave energy not directly absorbed by the reaction mixture was reflected at the end face of the cavity resonator opposite the coupling antenna; the microwave energy not absorbed by the reaction mixture also in the return and mirrored back in the direction of the magnetron was conducted by means of a prism system (circulator) into a vessel containing water. From the difference between incident energy and heating of this water load, the microwave energy introduced into the reaction mixture was calculated

By means of a high pressure pump and a suitable pressure relief valve, the reaction mixture was placed in the reaction tube under such a working pressure, which was sufficient to keep all starting materials and products or condensation products always in the liquid state. The ammonium salts prepared from carboxylic acid and amine were pumped through the reaction tube at a constant flow rate and the residence time in the irradiation zone was adjusted by modifying the flow rate.

The products were analyzed by means of ¹ H-NMR spectroscopy at 500 MHz in CDCl ₃ . The determination of iron contents was carried out by atomic absorption spectroscopy.

Example 1: Preparation of lactic acid N, N-dimethylamide

Dry ice cooling was used to condense 1.35 kg (30 mol) of dimethylamine from a storage bottle into a cold trap. In a three-necked flask with gas inlet tube, stirrer, internal thermometer and pressure equalization 2.7 kg (30 mol) of lactic acid were introduced and heated to 60 ⁰ C. By slowly thawing the cold trap, gaseous dimethylamine was passed through the gas inlet tube into the three-necked flask. In a strongly exothermic reaction, the lactic acid-NN-dimethylammonium salt formed. The ammonium salt thus obtained was continuously pumped through the reaction tube at a working pressure of about 25 bar at 5.0 l / h and subjected to a microwave power of 1.9 kW, of which 94% was absorbed by the reaction mixture. The residence time of the reaction mixture in the

Irradiation zone was about 34 seconds. At the end of the reaction tube, the reaction mixture had a temperature of 235 ⁰ C.

It was a turnover of 94% d. Th. Reached. The reaction product was slightly yellow in color and contained <2 ppm iron. The by-products which were inevitable in the thermal reaction (see Comparative Example 3) could not be detected (GC analysis, detection limit 0.1% by weight).

After distillative removal of the water of reaction on a thin film evaporator, the product was isolated at a boiling point of 105-108 ⁰ C (8 mbar) with a purity of 99.5% in 88% yield. The unreacted residues of the lactic acid N, N-dimethylammonium salt, which could be converted virtually quantitatively into the amide on renewed microwave irradiation, remained in the bottom.

Example 2: Preparation of lactic acid-N.N-diethylamide

Under cooling and stirring, 2.7 kg (30 mol) of lactic acid was added slowly with a 1:05 molar excess of diethylamine (2.3 kg, 31, 5 mol) and mixed (gas introduction see Example 1). After quenching of the heat of reaction, the resulting ammonium salt was heated to 80 ⁰ C and then pumped at a working pressure of about 25 bar continuously at 4.8 l / h through the reaction tube and a microwave power of 2.4 kW exposed, of which 95% of Reactive were absorbed. The residence time of the reaction mixture in the irradiation zone was about 35 seconds. At the end of the reaction tube, the reaction mixture had a temperature of 258 ⁰ C. It was a turnover of 97% d. Th. Achieved. The reaction product was dark yellow in color and contained <2 ppm iron. The product was freed of water and excess amine on the thin-film evaporator and could then be used without further purification.

Example 3 Production of Lactic Acid N, N-dimethylamide by Thermal Condensation (Comparative Example)

In a 500 ml glass flask with stirrer and descending intensive condenser, 180 g (2.0 mol) of lactic acid were placed and heated to 60 ⁰ C. Subsequently, 90.16 g (2.0 mol) of dimethylamine were introduced into the gas in gaseous form. By raising the temperature to 180 ⁰ C, the reaction was started. The forming during the reaction condensate water and unreacted dimethylamine were distilled off continuously After 20 hours, the reaction was stopped after no more water of reaction formed.

Based on the acid used, a conversion of 90% was found. It came during the reaction to a significant blackening of the reaction mixture. In addition, insoluble fractions formed, which indicated a partial decomposition of the reaction mixture. On the one hand oligomeric lactic acid polymers (5%) and on the other hand aminolysis products of lactic acid dimethylamide (2-dimethylamino-propionic acid dimethylamide) or lactic acid (4%) were detected as secondary components. Furthermore, in the exhaust no further quantified amounts of the elimination product acrylic acid-N, N-dimethylamide were found. Example 4 Production of Lactic Acid N, N-dimethylamide in the Single-Mode, Laboratory Microwave, Batch Reactor (Comparative)

A melt of the lactic acid N, N-dimethylammonium salt was prepared by the method described in the previous example.

From this melt, 2 ml were pressure sealed into a pressure resistant vial and placed in the microwave cavity of a "Biotage Initiator ™" laboratory microwave oven, which was then heated to 240 ° C within one minute by applying a microwave power of 250 watts At the end of the heating-up period, the sample was irradiated with regulated power for a further 4 minutes, adjusting the performance such that the temperature of the reaction mixture remained constant at 240 ^° C.

Based on the acid used, a conversion of 45% was found in the crude product. The product had a dark brown to black color. Here, too, black particles were formed, which could be separated by a filter. This solid could not be dissolved in any common solvent, which can be taken as an indication that these are pyrolysis products of the reaction mixture. Polymeric structures as described in the previous comparative example were not observed.

Example 5: Preparation of 3-hydroxybutyric acid dimethylamide

2.6 kg (25 mol) of 3-hydroxybutanoic acid were dissolved in 2 liters of toluene in a 10 liter stirred autoclave (Büchi). Subsequently, the acid was converted with cooling by introducing an equimolar amount of gaseous dimethylamine into the ammonium salt (procedure according to Example 1). After quenching of the heat of reaction, the ammonium salt thus obtained was pumped through the reaction tube at a working pressure of about 25 bar continuously at 3.0 l / h and o U

a microwave power of an average of 1, 85 kW exposed, of which 88% were absorbed by the reaction mixture. The residence time of the reaction mixture in the irradiation zone was about 57 seconds. At the end of the reaction tube, the reaction mixture had a temperature of 244 ⁰ C.

It was a turnover of 92% d. Th. Reached. The reaction product was brown in color and showed no signs of polymer formation. Aminolysis products such as 3-N, N-dimethylaminobutyric acid or 3-N, N-Dimethylaminobuttersäuredimethylamid could not be detected in the crude product mixture. The content of iron was

<2 ppm iron. The 3-hydroxybutyric acid dimethylamide was isolated by evaporation of toluene and the resulting water of reaction.

Example e: Preparation of ricinoleic acid dimethylamide

2.98 kg (10 mol) of 12-hydroxy-9-octadecenoic acid (ricinoleic acid) were dissolved in 2 liters of toluene in a 10 liter stirred autoclave (Büchi). The acid was then converted into the ammonium salt with cooling by introducing an equimolar amount of gaseous dimethylamine (0.45 kg) (procedure according to Example 1). After quenching of the heat of reaction, the resulting ammonium salt was pumped at a working pressure of about 25 bar continuously at 3.5 l / h through the reaction tube and a microwave power averaged 2.1 kW exposed, of which 89% were absorbed by the reaction. The residence time of the reaction mixture in the irradiation zone was about 49 seconds. At the end of the reaction tube, the reaction mixture had a temperature of 240 ^° C.

It was a turnover of 90% d. Th. Reached. The reaction product was colored yellowish brown. Aminolysis products could not be detected even in this example in the crude product mixture. The content of iron was <2 ppm. Despite high reaction temperature were in the context of Measurement accuracy of ¹ H NMR found no evidence of a reaction of the C = C double bond in the center of the molecule.

Example 7: Preparation of Mevalonic Acid Dimethylamide

2.96 kg (20 mol) of racemic 3,5-dihydroxy-3-methylpentanoic acid (mevalonic acid) were introduced into a 10 liter stirred autoclave (Büchi) with heating at 60 ⁰ C in 4 liters of toluene dispersed. Subsequently, the acid was slowly converted by introducing 945 g of gaseous dimethylamine (21 mol) into the ammonium salt (procedure according to Example 1). After quenching of the heat of reaction, the resulting ammonium salt was pumped continuously at 4 l / h through the reaction tube at a working pressure of about 25 bar and exposed to a microwave power of 2.25 kW average, of which 88% were absorbed by the reaction. The residence time of the reaction mixture in the irradiation zone was about 42 seconds. At the end of the reaction tube, the reaction mixture had a temperature of 250 ⁰ C. It was a conversion of 92% d. Th. Reached. The reaction product was colored yellowish red. Neither aminolysis products nor polymers could be detected in the crude product mixture. The content of iron was <2 ppm. The desired product 3,5-dihydroxy-3-methylpentansäuredimethylamid was isolated after evaporation of the toluene and the resulting reaction water.

Claims

claims

1. A continuous process for the preparation of hydroxycarboxylic acid amides by reacting at least one hydroxycarboxylic acid of the formula I

HO-R ³ -COOH (I)

HNR ¹ R ² (II)

wherein R ¹ and R ^{2 are} independently hydrogen or a hydrocarbon group having 1 to 100 carbon atoms, is reacted to an ammonium salt and this ammonium salt subsequently under microwave irradiation in a reaction tube whose longitudinal axis is in the propagation direction of the microwaves of a single-mode microwave applicator , is converted to Hydroxycarbonsäureamid.

2. The method of claim 1, wherein the irradiation of the salt with microwaves in a substantially microwave-transparent reaction tube within a waveguide connected to a microwave generator via waveguide takes place.

3. The method according to one or more of claims 1 and 2, wherein the microwave applicator is designed as a cavity resonator.

4. The method according to one or more of claims 1 to 3, wherein the microwave applicator is designed as a cavity resonator of the reflection type.

5. The method according to one or more of claims 1 to 4, wherein the reaction tube is aligned axially with a central axis of symmetry of the waveguide.

6. The method according to one or more of claims 1 to 5, wherein the irradiation of the salt takes place in a cavity resonator with coaxial transition of the microwaves.

7. The method according to one or more of claims 1 to 6, wherein the cavity resonator is operated in Eoi _n mode, where n is an integer from I to 200.

8. The method according to one or more of claims 1 to 7, wherein R ^{3 contains} 1 to 30 carbon atoms.

9. The method according to one or more of claims 1 to 8, wherein R ^{3 contains} at least one bound to a secondary carbon atom OH group.

10. The method according to one or more of claims 1 to 9, wherein R ^{3 contains} a hydroxyl group in α-position to the carboxyl group.

11. The method according to one or more of claims 1 to 10, wherein R ^{3 contains} one or more double bonds.

12. The method according to one or more of claims 1 to 11, wherein R ^{3 is} one or more substituents selected from halogen atoms, halogenated alkyl radicals, Ci-C ₅ -Aikoxy-, poly (Ci-C ₅ alkoxy) -, poly (C -CC ₅ alkoxy) alkyl, carboxyl, hydroxyl, ester, amide, cyano, nitrile, nitro and aryl groups having 5 to 20 carbon atoms, wherein the C ₅ -C ₂ o-aryl groups substituents selected from halogen atoms, C ₁ -C _2O -AI alkyl-, C ₂ -C ₂ o-alkenyl, _Ci-C5 alkoxy, ester, amide, hydroxy, cyano, nitrile, and / or Can carry nitro groups.

13. The method according to one or more of claims 1 to 12, wherein R ¹ and R ^{2 are} independently a hydrocarbon radical having 1 to 100 carbon atoms.

14. The process as claimed in one or more of claims 1 to 12, in which R ^{1 represents an} internal hydrocarbon radical having from 1 to 100 carbon atoms and R ^{2 is} hydrogen.

15. The method according to one or more of claims 1 to 14, wherein R ¹ or R ² or both radicals substituents selected from d-Cs-alkoxy, cyano,

Nitrile, nitro and C ₅ -C ₂ o-aryl groups wear.

16. The method according to one or more of claims 1 to 15, wherein R ¹ or R ² or both radicals carry C ₅ -C ₂ o-aryl groups, and these one or more substituents selected from halogen atoms, halogenated

Alkyl radicals, C ₁ -C _2O -AIKyI, C ₂ -C _2O -AI kenyl, C ₁ -C ₅ alkoxy, hydroxyl, ester, amide, cyano, nitrile, and nitro groups.

17. The method according to one or more of claims 1 to 12 and 15, wherein R ¹ and R ² form a ring together with the nitrogen atom to which they are attached.

18. The method according to one or more of claims 1 to 12, wherein R ¹ and R ² independently of one another for radicals of the formula III

- (R ⁴ -O) _n -R ⁵ (IM)

stand in which

R ^{4 is} an alkylene group having 2 to 6 C atoms, R ^{5 is} a hydrocarbon radical having 1 to 24 C atoms or a

Group of the formula NR ¹⁰ R ¹¹ , n for a number between 2 and 50 and

R ¹⁰ , R ¹¹ independently represent an aliphatic radical with 1 to 24 C atoms and preferably 2 to 18 C atoms, an aryl group or heteroaryl group having 5 to 12 ring members, a poly (oxyalkylene) group having 1 to 50 poly (oxyalkylene) units, wherein the polyoxyalkylene units of alkylene oxide units having 2 to 6 Derive C atoms, or R ¹⁰ and R ¹¹ together with the

19. The method according to one or more of claims 1 to 12, wherein R ¹ and R ^{2 are} independently of one another radicals of the formula IV

- [R ⁶ -N (R ⁷ )] _m - (R ⁷ ) (IV)

wherein R ^{6 is} an alkylene group having 2 to 6 C atoms or mixtures thereof, each R ^{7 is} independently hydrogen, an alkyl or

Hydroxyalkyl radical having up to 24 carbon atoms, a polyoxyalkylene radical - (R ⁴ -O) _p -R ⁵ , or a polyiminoalkylene radical - [R ⁶ -N (R ⁷ )] _q - (R ⁷ ), where R ⁴ , R ⁵ , R ⁶ and R ^{7 have} the meanings given above and q and p independently of one another are from 1 to 50, and m is a number from 1 to 20 and preferably from 2 to 10, for example three, four, five or six.

20. The method according to one or more of claims 1 to 19, wherein the microwave irradiation is carried out at temperatures between 150 and 500 ⁰ C.

21. The method according to one or more of claims 1 to 20, wherein the microwave irradiation takes place at pressures above atmospheric pressure.

22. The method according to one or more of claims 1 to 15, 17, 20 and 21, wherein R ¹ or R ² or both substituents independently represent an aliphatic radical having 1 to 24 carbon atoms.

23. Hydroxycarboxylic acid amides with a low metal content, prepared by reacting at least one hydroxycarboxylic acid of the formula I.

HO-R ³ -COOH (I)

wherein R ^{3 is} an optionally substituted aliphatic hydrocarbon radical having 1 to 100 carbon atoms, with at least one amine of the formula

HNR ¹ R ² (II)

wherein R ¹ and R ^{2 are} independently hydrogen or a hydrocarbon radical having 1 to 100 carbon atoms, to an ammonium salt and subsequent reaction of this ammonium salt to Hydroxycarbonsäureamid under microwave irradiation in a reaction tube whose longitudinal axis is in the propagation direction of the microwaves of a single-mode microwave applicator located.