Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C231/00—Preparation of carboxylic acid amides
  • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
  • B01J19/12—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electromagnetic waves
  • B01J19/122—Incoherent waves
  • B01J19/126—Microwaves
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D213/81—Amides; Imides
  • C07D213/82—Amides; Imides in position 3

Definitions

• Amides of aromatic carboxylic acids are widely used as chemical raw materials.
• various amides are used as intermediates for the production of pharmaceuticals and agrochemicals.
• tertiary amides of aromatic carboxylic acids and especially tertiary amides of Alkylphenylcarbonklaren are a pharmacologically and technically very interesting class of compounds.
• amides of alkylbenzoic acids with secondary alkylamines find use as insect repellents (repellents).
• Vazquez-Tato Synlett 1993, 506, discloses the use of microwaves as a heating source for the production of amides from carboxylic acids and arylaliphatic amines via the ammonium salts.
• the yields of aromatic carboxylic acids with primary amines are considered moderate, those with secondary amines low.
• the syntheses were carried out on a mmol scale.
• the inhomogeneity of the microwave field caused by localized overheating of the reaction mixture is caused by more or less uncontrolled reflections of the microwaves radiated into the microwave oven on its walls and in the reaction mixture, is caused by the commonly used multimode radiation.
• Microwave ovens Problems with scale-up.
• the microwave absorption coefficient of the reaction mixture which often changes during the reaction, presents difficulties with regard to a reliable and reproducible reaction.
• 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
• a process has therefore been sought for the preparation of amides of aromatic carboxylic acids, in which aromatic carboxylic acid and amine are also converted to the amide on an industrial scale under microwave irradiation can.
• the aim is to achieve as high as possible, that is to say quantitative, conversion rates.
• the method should continue to allow a possible energy-saving production of carboxylic acid amides, that is, the microwave power used should be absorbed as quantitatively as possible from the reaction mixture and the process thus a high energy
• 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.
• amides of aromatic carboxylic acids are obtained by direct reaction of aromatic carboxylic acids with amines in a continuous process by only brief heating by irradiation with microwaves in a reaction tube whose longitudinal axis is in the propagation direction of the microwaves of a monomode.
• Microwave applicator can be produced in high yields and in technically relevant quantities.
• 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 amides of aromatic carboxylic acids by at least one aromatic carboxylic acid of the formula I.
• Ar is an optionally substituted aryl radical having 5 to 50 atoms, with at least one amine of the formula II
• 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 the carboxylic acid amide.
• Ar is preferably an aryl radical bearing at least one carboxyl group bonded to an aromatic system.
• aromatic systems is meant cyclic (4n + 2) ⁇ electron conjugated systems in which n is a natural integer and preferably 1, 2, 3, 4 or 5.
• the aromatic system may be mono- or polycyclic, such as di- or tricyclic.
• the aromatic system is preferably formed from carbon atoms. In a further preferred embodiment, it contains, in addition to carbon atoms, one or more heteroatoms, such as, for example, nitrogen, oxygen and / or sulfur. Examples of such aromatic systems are benzene, naphthalene, phenanthrene, furan and pyridine.
• the aromatic system may carry, in addition to the carboxyl group, one or more, for example, one, two, three or more identical or different further substituents.
• Suitable further substituents are, for example, alkyl, alkenyl and halogenated alkyl radicals, hydroxy, hydroxyalkyl, alkoxy, poly (alkoxy), halogen, carboxyl, amide, cyano, nitrile, nitro and / or sulfonic acid groups , These substituents may be attached at any position of the aromatic system.
• the aryl radical carries at most as many substituents as it has valencies.
• the aryl radical Ar of the formula (I) carries further carboxyl groups.
• the process according to the invention is likewise for the reaction of aromatic carboxylic acids with, for example, two or more Suitable carboxyl groups.
• imides can also be formed.
• alkylarylcarboxylic acids such as, for example, alkylphenylcarboxylic acids.
• alkylarylcarboxylic acids such as, for example, alkylphenylcarboxylic acids.
• aromatic carboxylic acids in which the aryl radical Ar bearing the carboxyl group additionally carries at least one alkyl or alkylene radical.
• the process is particularly advantageous in the amidation of
• Alkylbenzoic acids which carry at least one alkyl radical having 1 to 20 carbon atoms and in particular 1 to 12 carbon atoms such as 1 to 4 carbon atoms.
• Suitable aromatic carboxylic acids include benzoic acid, phthalic acid, isophthalic acid, the various isomers of naphthalenedicarboxylic acid, pyridinecarboxylic acid and naphthalenedicarboxylic acid and trimellitic acid, trimesic acid, pyromellitic acid and mellitic acid, the various isomers of methoxybenzoic acid, hydroxybenzoic acid, hydroxymethyl benzoic acid, Hydroxymethoxybenzoeklare, Hydroxydimethoxybenzoeklare, hydroxyisophthalic acid, hydroxynaphthalenecarboxylic, Hydoxypyridincarbonklare and Hydroxymethylpyridincarbonklare , Hydroxyquinolinecarboxylic acid and o-toluic acid, m-toluic acid, p-toluic acid, o-ethylbenzoic acid, m-ethylbenzoic acid, p-ethylbenzoic acid, o-
• the process according to the invention is preferably suitable for the preparation of secondary amides, ie for the reaction of aromatic carboxylic 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 amides, that is to say for the reaction of aromatic carboxylic acids with amines, in which both radicals R 1 and R 2 independently of one another represent 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.
• 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 carry substituents such as, for example, hydroxyl, C 1 -C 5 -alkoxy, cyano, nitrile, nitro and / or C 5 -C 20 -aryl groups, for example phenyl radicals.
• the C 5 -C 2 o-aryl radicals may in turn optionally with halogen atoms, CrC 2 o-alkyl, C 2 -C 2 o-alkenyl, hydroxyl, Ci-Cs-alkoxy such as methoxy, amide, cyano , Nitrile, and / or nitro groups substituted.
• Particularly preferred aliphatic radicals are methyl, ethyl, hydroxyethyl, n-propyl, isopropyl, hydroxypropyl, n-butyl, isobutyl and tert-butyl, hydroxybutyl, n-hexyl, cyclohexyl, n-octyl, n-decyl, n-dodecyl, tridecyl, isotridecyl, tetradecyl, hexadecyl, octadecyl and methylphenyl.
• R 1 and / or R 2 are independently hydrogen, C- ⁇ -C 6 alkyl, C 2 -C 6 -alkenyl or C 3 -C 6 cycloalkyl radical and especially an alkyl radical with 1, 2, or 3 C atoms. These radicals can carry up to three substituents.
• 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.
• 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.
• R 1 and / or R 2 independently of one another are an alkyl radical interrupted by heteroatoms. Particularly preferred heteroatoms are oxygen and nitrogen.
• R 1 and / or R 2 independently of one another are preferably radicals of the formula III
• R 4 is an alkylene group having 2 to 6 carbon atoms and preferably 2 to
• R 5 is hydrogen, a hydrocarbon radical having 1 to 24 C atoms or a group of the formula -NR 10 R 11 , n is a number between 2 and 50, preferably between 3 and 25 and especially between 4 and 10 and
• R 10 , R 11 independently of one another represent hydrogen, an aliphatic radical having 1 to 24 C atoms and preferably 2 to 18 C atoms, an aryl group radical or heteroaryl group having 5 to 12 ring members, a poly (oxyalkylene) group having 1 to 50 poly (oxyalkylene) units, wherein the polyoxyalkylene units are derived from alkylene oxide units having 2 to 6 C atoms, or R 10 and R 11 together with the nitrogen atom, to which they are bound, form a ring with 4, 5, 6 or more ring links.
• R 1 and / or R 2 independently of one another are preferably radicals of the formula IV
• R 6 is an alkylene group having 2 to 6 C atoms and preferably having 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 ), wherein R 4 , R 5 , R 6 and R 7 have the meanings given above and q and p are independently from 1 to 50 and m is a number from 1 to 20 and preferably 2 to 10 such as three, four , five or six stands.
• the radicals of the formula IV preferably contain 1 to 50, in particular 2 to 20, nitrogen atoms.
• one or more amino groups are converted into the carboxylic acid amide.
• the primary amino groups can also be converted into imides.
• nitrogen-containing compounds which split off when heated ammonia gas used.
• nitrogen-containing compounds are urea and formamide.
• Suitable amines are ammonia, methylamine, ethylamine,
• Di-iso-propylamine, ethylmethylamine and N, N-dimethylaminopropylamine Di-iso-propylamine, ethylmethylamine and N, N-dimethylaminopropylamine.
• the process is particularly suitable for preparing N, N-dimethylbenzamide, N, N-diethylbenzamide, N, N- (2-hydroxyalkyl) benzamide, N, N-dimethylnicotinamide and N, N-dimethyltolyl acid amide.
• aromatic carboxylic acid and amine can generally be reacted with one another in any desired ratios.
• the reaction between carboxylic acid and amine preferably takes place with molar ratios of from 10: 1 to 1: 100, preferably from 2: 1 to 1:10, especially from 1.2: 1 to 1: 3, in each case based on the molar equivalents of carboxyl groups. and amino groups.
• carboxylic acid and amine are used equimolar.
• an excess of amine that is to say molar ratios of amine to carboxyl groups of at least 1:01: 00 and in particular between 50: 1 and 1: 02: 1, for example between 10: 1 and 1, 1: 1 work.
• the carboxyl groups are converted virtually quantitatively to the amide. This method is particularly advantageous if the amine used is light is fleeting. 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.
• R 1 and / or R 2 are a hydrocarbon radical substituted by one or more hydroxyl groups
• the reaction between aromatic carboxylic acid and amine takes place with molar ratios of 1: 1 to 1: 100, preferably 1: 1, 001 to 1:10 and especially from 1: 1, 01 to 1: 5, for example from 1: 1, 1 to 1: 2, in each case based on the molar equivalents of carboxyl groups and amino groups in the reaction mixture.
• the reaction takes place between aromatic carboxylic acid and amine with molar ratios of 1: 100 to 1: 1, preferably from 1:10 to 1: 1, 001 and especially from 1: 5 to 1: 1, 01 such as from 1: 2 to 1: 1, 1, in each case based on the molar equivalents of carboxyl groups and amino groups in the reaction mixture.
• R 1 and / or R 2 are a hydrocarbon radical substituted by one or more hydroxyl groups and the aryl radical Ar carries one or more hydroxyl groups
• the reaction between aromatic carboxylic acid and amine takes place equimolar relative to the molar equivalents of carboxyl groups and amino groups in the reaction mixture.
• the amides according to the invention are prepared by reacting aromatic 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.
• 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.
• 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.
• the electric field is directed toward the central axis of symmetry of the cavity resonator. 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.
• 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, 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.
• the irradiation of the ammonium salt with microwaves in a reaction tube which is located in a waveguide with coaxial transition of the microwaves.
• particularly preferred microwave devices are made of a cavity resonator, a coupling device for coupling a microwave field in the
• Cavity resonator and constructed with one opening at two opposite end walls for passing the reaction tube through the resonator.
• the coupling of the microwaves into the cavity resonator takes place preferably 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.
• 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.
• 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.
• 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.
• 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.
• the reaction tube is guided through the cavity of an inner conductor tube acting as a coupling antenna into the cavity resonator.
• Microwave generators such as the magnetron, the klystron and the gyrotron are known in the art.
• the reaction tubes used for carrying out the method according to the invention are preferably made of largely microwave-transparent, high-melting material.
• Non-metallic reaction tubes are particularly preferably used.
• Substantially microwave-transparent materials are understood here which absorb as little microwave energy as possible and convert it into heat.
• the dielectric loss factor tan ⁇ is defined as the ratio of the dielectric loss ⁇ " and the dielectric constant ⁇ ' , Examples of tan ⁇ values of various materials are given, for example, in D. Bogdal, Microwave Assisted Organic Synthesis, Elsevier 2005.
• microwave-transparent and temperature-stable materials are primarily materials based on minerals such as quartz, alumina, zirconia and the like into consideration.
• 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.
• PEEK glass fiber reinforced polyetheretherketone
• reaction tubes have an inner diameter of one millimeter to about 50 cm, especially between 2 mm and 35 cm such as 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.
• baffles and / or other mixing elements can be installed.
• 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 the 1, 0- to
• the Eoi cavity resonator has a round cross-section, which also as
• Eor round hollow conductor is called. Most preferably, it has a cylindrical
• 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.
• 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.
• the educts amine and carboxylic acid, both independently of one another optionally diluted with solvent, are mixed shortly before they enter the reaction tube.
• the educts are fed to the process according to the invention in liquid form.
• 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.
• 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 may be fed into the reaction tube either at the end guided through the inner conductor tube, as well as at the opposite end.
• 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 direction of propagation of the microwaves of a single-mode microwave applicator and in particular within a Eoi cavity resonator, for 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.
• the inventive method also allows a controlled, safe and reproducible reaction. Since the reaction mixture is moved in the reaction tube parallel to the direction of propagation of the microwaves, known overheating phenomena by uncontrollable field distributions, which lead to local overheating by changing intensity of the field, for example in wave crests and nodes, by the flow of the
• Ammonium salt in the microwave field a very extensive amidation with conversions in general of over 80%, often over 90% such as more than 95% based on the component used in the deficit occurs, without formation of appreciable amounts of by-products.
• these ammonium salts in a flow tube of the same dimensions under thermal jacket heating extremely high wall temperatures are required to achieve suitable reaction temperatures, which led to the formation of colored species, but cause only minor amide formation at the same time interval.
• the products produced by the process according to the invention have very low metal contents without the need for further processing of the crude products.
• 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.
• 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.
• the implementation of the reaction has proven particularly useful at temperatures between 150 and 400 ° C. and especially between 180 and 300 ° C., for example at temperatures between 200 and 270 ° 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 over a Period of less than 30 minutes, preferably between 0.01 seconds and 15 minutes, more preferably between 0.1 seconds 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.
• the reaction product is cooled as soon as possible after completion of the microwave irradiation to temperatures below 120 0 C, preferably below 100 0 C and especially below 60 0 C.
• the reaction is carried out at pressures between 0.01 and 500 bar and more preferably between 1 bar (atmospheric pressure) and 150 bar and especially 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.
• an inert protective gas such as nitrogen, argon or helium.
• the reaction is accelerated or completed in the presence of dehydrating catalysts.
• dehydrating catalysts Preferably, one works in the presence of an acidic inorganic, organometallic or organic catalyst or mixtures of several of these catalysts.
• acidic inorganic catalysts for example, sulfuric acid, phosphoric acid, phosphonic acid, hypophosphorous acid, aluminum sulfate hydrate, alum, acidic silica gel and acidic aluminum hydroxide.
• aluminum compounds of the general formula AI (OR 15 ) 3 and titanates of the general formula Ti (OR 15 J 4 can be used as acidic inorganic catalysts, wherein the radicals R 15 may be the same or different and are independently selected from CiC-io 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 Cyclo
• Preferred acidic organometallic catalysts are, for example, selected from dialkyltin oxides (R 15 J 2 SnO, where R 15 is defined standing as above.
• dialkyltin oxides R 15 J 2 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.
• 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.
• titanates of the general formula Ti (OR 15 ) 4 and especially titanium tetrabutylate and titanium tetraisopropylate are particularly preferred for carrying out the process according to the invention.
• acidic inorganic, organometallic or organic catalysts according to the invention 0.01 to 10% by weight, preferably 0.02 to 2% by weight, of catalyst is used. In a particularly preferred embodiment, working without a catalyst.
• the microwave irradiation is carried out in the presence of acidic solid catalysts.
• 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.
• suitable solid catalysts are zeolites, silica gel, montmorillonite and (partially) crosslinked polystyrenesulphonic acid, which may optionally be impregnated with catalytically active metal salts.
• Solid phase catalysts can be used, for example, from Rohm & Haas under the brand name Amberlyst ® available.
• Reaction mixture if heterogeneous, to fluidize.
• all solvents can be used which are inert under the reaction conditions used and not with the educts or the formed React to products.
• 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 ⁇ . "The dielectric loss ⁇ " 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
• Solvents which are preferred for the process according to the invention have a dielectric loss ⁇ "of less than 10 and preferably less than 1, for example less than 0.5, measured at room temperature and 2450 MHz An overview of the dielectric loss of various solvents can be found, for example, in" Microwave Synthesis "by BL Hayes, CEM Publishing 2002.
• Suitable solvents for the process according to the invention are, in particular, solvents having ⁇ " values below 10, such as N-methylpyrrolidone, N, N-dimethylformamide or acetone, and in particular solvents having ⁇ "values below 1.
• EXAMPLES for particularly preferred solvents with ⁇ "values below 1 are aromatic and / or aliphatic hydrocarbons such as toluene, xylene, ethylbenzene, tetralin, hexane, cyclohexane, decane, pentadecane, decalin and commercial hydrocarbon mixtures such as gasoline fractions, kerosene, solvent naphtha, ® Shellsol AB, ® Solvesso 150, ® Solvesso 200, ® Exxs ol, ® isopar and ® Shellsol types.
• Solvent mixtures which have ⁇ "values preferably below 10 and especially below 1 are equally preferred for carrying out the process according to the invention.
• the process according to the invention can also be carried out in solvents having higher ⁇ "values of, for example, 5 and higher, in particular with ⁇ " values of 10 and higher.
• ⁇ values of, for example, 5 and higher
• ⁇ values of 10 and higher.
• 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 .-%.
• 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.
• microwave radiation with the frequencies released for industrial, scientific and medical applications is preferably used, for example with frequencies of 915 MHz, 2.45 GHz, 5.8 GHz or 27.12 GHz.
• microwave power to be radiated into the cavity resonator for carrying out the method according to the invention is in particular dependent on the geometry of the reaction tube and thus of 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.
• 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.
• 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.
• the water of reaction formed is after cooling and / or relaxation by conventional methods such as phase separation, distillation stripping, flashing and / or absorption separated.
• amides prepared via the route according to the invention are obtained in a sufficient purity for further use.
• 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 aromatic 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. Particularly surprising was the observation that arylcarboxylic acids and in particular alkylarylcarboxylic acids such as, for example, alkylphenylcarboxylic acids under the conditions of the process according to the invention show no appreciable decarboxylation.
• amides of aromatic carboxylic acids prepared by the process according to the invention are often so pure that no further work-up or post-processing steps are required. Since they are due to the process no residues of coupling reagents or their Contain derived products, they can easily be used in toxicologically sensitive areas such as cosmetic and pharmaceutical preparations.
• Cavity resonator passed through the ceramic tube through the cavity of a functioning as a coupling antenna inner conductor tube.
• the 2.45 GHz frequency microwave field generated by a magnetron was coupled into the cavity by means of the coupling antenna (Eor cavity applicator, monomode).
• 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 carried out directly after leaving the reaction zone (about 15 cm distance in an insulated stainless steel capillary, 0 1 cm) by means of 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 which was not absorbed by the reaction mixture during the return and was reflected back in the direction of the magnetron was conducted by means of a prism system (circulator) into a vessel containing water.
• 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.
• the mixture thus obtained was continuously pumped through the reaction tube at 3.5 l / h at a working pressure of 30 bar and subjected to a microwave power of 2.3 kW, of which 88% was absorbed by the reaction mixture.
• the residence time of the reaction mixture in the irradiation zone was about 49 seconds.
• the reaction mixture had a temperature of 290 0 C.
• the molten salt thus obtained was continuously pumped through the reaction tube at 3 l / h at a working pressure of 35 bar and subjected to a microwave power of 2.5 kW, of which 94% was absorbed by the reaction mixture.
• Irradiation zone was about 57 seconds.
• the reaction mixture had a temperature of 295 ° C.
• the resulting mixture was pumped through the reaction tube continuously at 4 l / h at a working pressure of 30 bar and subjected to a microwave power of 2.5 kW, of which 89% was absorbed by the reaction mixture.
• the residence time of the reaction mixture in the irradiation zone was about 43 seconds.
• the reaction mixture had a temperature of 288 0 C.
• reaction solution in a 1 liter stirred autoclave, 500 ml of reaction solution (sample preparation see Example 2) were presented together with 2 g of iron filings and heated in closed apparatus with maximum heating power with vigorous stirring within 12 minutes at 290 0 C (oil flow temperature 370 0 C). Under pressure, the reaction mixture was stirred for 10 minutes and then cooled to room temperature through a Kaitölnikank. The reaction mixture thus treated showed a conversion of only 8% of the theoretically possible yield (based on the m-toluic acid used in the deficit). The reaction mixture was discolored black-brown after the reaction and had a markedly hot smell. An analysis of the metal content of the reaction material yielded a value of 57 ppm iron.

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