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
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C233/00—Carboxylic acid amides
  • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
  • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
  • C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
  • C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
  • C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
  • C07C303/22—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof from sulfonic acids, by reactions not involving the formation of sulfo or halosulfonyl groups; from sulfonic halides by reactions not involving the formation of halosulfonyl groups
• • H—ELECTRICITY
  • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
  • H05B—ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL
  • H05B6/00—Heating by electric, magnetic or electromagnetic fields
  • H05B6/64—Heating using microwaves
  • H05B6/70—Feed lines
  • H05B6/701—Feed lines using microwave applicators
• • H—ELECTRICITY
  • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
  • H05B—ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL
  • H05B6/00—Heating by electric, magnetic or electromagnetic fields
  • H05B6/64—Heating using microwaves
  • H05B6/80—Apparatus for specific applications
  • H05B6/806—Apparatus for specific applications for laboratory use
• • 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
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00002—Chemical plants
  • B01J2219/00027—Process aspects
  • B01J2219/00033—Continuous processes
• • 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
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
  • B01J2219/0873—Materials to be treated
  • B01J2219/0881—Two or more materials
  • B01J2219/0888—Liquid-liquid
• • 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
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
  • B01J2219/0873—Materials to be treated
  • B01J2219/0892—Materials to be treated involving catalytically active material
• • 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
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
  • B01J2219/12—Processes employing electromagnetic waves
  • B01J2219/1203—Incoherent waves
  • B01J2219/1206—Microwaves
  • B01J2219/1209—Features relating to the reactor or vessel
  • B01J2219/1221—Features relating to the reactor or vessel the reactor per se
  • B01J2219/1224—Form of the reactor
  • B01J2219/1227—Reactors comprising tubes with open ends

Definitions

• the present invention relates to a continuous process for the acylation of amino acids bearing organic acids under microwave irradiation on an industrial scale.
• Acylation products of organic acids carrying amino groups find versatile uses as chemical raw materials.
• N-acylated amino-bearing organic acids in particular as
• Vazquez-Tato, Synlett 1993, 506 discloses the use of microwaves as a heat source for the production of amides from carboxylic acids and
• arylaliphatic amines via the ammonium salts.
• the syntheses are carried out on a mmol scale.
• Plasmas formation set narrow limits. Furthermore, prepares the leading in multi-mode microwave ovens to local overheating of the reaction material, caused by more or less uncontrolled reflections of the microwaves irradiated in the microwave oven on the walls and the reaction mixture caused inhomogeneity of the microwave field problems in scale-up. In addition, the microwave absorption coefficient of the reaction mixture, which frequently changes during the reaction, presents difficulties with regard to a reliable and reproducible reaction procedure.
• Multimode microwave applicators on the applicator more or less homogeneously distributed and not focused on the coil
• single-mode or single-mode microwave applicators are known in which working with a single microwave mode, which propagates in only one spatial direction and is focused by precisely dimensioned waveguides on the reaction vessel.
• 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.
• N-acylation products of amino acids carrying organic acids by direct reaction of carboxylic acids with amino acids carrying organic acids in one continuous process by only brief heating by irradiation with microwaves in a reaction tube whose longitudinal axis in the
• Propagation direction of the microwaves of a single-mode microwave applicator can be produced 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 invention relates to a continuous process for the N-acylation of amino acids carrying amino groups, in which at least one
• Hydrocarbon radical having 1 to 50 carbon atoms, with at least one at least one amino-bearing organic acid of the formula (II)
• A is an optionally substituted hydrocarbon radical having 1 to 50 carbon atoms
• R 2 is hydrogen, an optionally substituted hydrocarbon radical having 1 to 50 carbon atoms or a group of the formula -AX, in which A is as also X independently of one another have the meanings given above,
• Carboxylic acids of the formula I are generally compounds which have at least one carboxyl group on an optionally substituted
• Hydrocarbon radical having 1 to 50 carbon atoms and formic acid.
• the hydrocarbon radical may be aliphatic or aromatic.
• the hydrocarbon radical R 1 is an aliphatic, unsubstituted alkyl or alkenyl radical.
• the aliphatic hydrocarbon radical bears one or more, for example two, three, four or more further substituents.
• Suitable substituents are, for example, halogen atoms, halogenated
• Alkyl radicals C- ⁇ -C 5 alkoxy such as methoxy, poly (C 1 -C 5 -alkoxy) -, poly (-C 5 alkoxy) alkyl, carboxyl, amide, cyano, nitrile, Nitro and / or aryl groups having 5 to 20 carbon atoms such as phenyl groups, with the proviso that these 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 can in turn substituents such as halogen atoms, halogenated alkyl radicals, CrC 2 O-alkyl,
• Ci-Cs-alkoxy such as methoxy, ester, amide, cyano, nitrile and / or nitro groups.
• hydrocarbon radical carries at most as many substituents as it has valencies.
• the aliphatic bears
• Hydrocarbon radical R 1 one or more further carboxyl groups.
• the process according to the invention is also suitable for the N-acylation of organic acids carrying amino groups with polycarboxylic acids which carry, for example, two, three, four or more carboxyl groups.
• Carboxyl groups of the polycarboxylic acid (I) are completely or partially amidated.
• the Amid istsgrad can be, for example, by the Adjust stoichiometry between carboxylic acid (I) and amino acid-carrying organic acid (II) in the reaction mixture.
• the aliphatic hydrocarbon radical R 1 carries no amino groups.
• carboxylic acids (I) which carry an aliphatic hydrocarbon radical having 1 to 30 carbon atoms and in particular having 2 to 24 carbon atoms, for example having 3 to 20 carbon atoms. They can be natural or synthetic.
• the aliphatic acids (I) which carry an aliphatic hydrocarbon radical having 1 to 30 carbon atoms and in particular having 2 to 24 carbon atoms, for example having 3 to 20 carbon atoms. They can be natural or synthetic.
• the aliphatic acids (I) which carry an aliphatic hydrocarbon radical having 1 to 30 carbon atoms and in particular having 2 to 24 carbon atoms, for example having 3 to 20
• Hydrocarbon radical 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 aliphatic hydrocarbon radicals 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.
• cyclic aliphatic hydrocarbon radicals have at least one ring with four, five, six, seven, eight or more ring atoms.
• R 1 is a saturated alkyl radical having 1, 2, 3 or 4 C atoms. This can be linear or branched.
• Carboxyl group may be bonded to a primary, secondary or, as in the case of pivalic acid, tertiary C atom.
• the alkyl radical is an unsubstituted alkyl radical.
• the alkyl radical carries one to nine, preferably one to five, for example two, three or four further
• Preferred further substituents are carboxyl groups and optionally substituted Cs-Cao-aryl radicals.
• the aforementioned substituents are carboxyl groups and optionally substituted Cs-Cao-aryl radicals.
• Carboxylic acid (I) to an ethylenically unsaturated carboxylic acid is an optionally substituted alkenyl group having 2 to 4 carbon atoms.
• the alkenyl group may be linear or, if it comprises at least three carbon atoms, branched.
• the alkenyl radical is an unsubstituted alkenyl radical.
• R 1 is particularly preferably an alkenyl radical having 2 or 3 C atoms.
• the alkenyl radical bears one or more, for example two, three or more further substituents.
• the alkenyl radical carries at most as many substituents as it has valencies. In particularly preferred embodiments of the carries
• Alkenyl radical R 1 as further substituents a carboxyl group or an optionally substituted C 5 -C 2 o-aryl group.
• the inventive method is also suitable for the reaction of ethylenically unsaturated dicarboxylic acids.
• R 1 is an optionally substituted aliphatic hydrocarbon radical having 5 to 50 carbon atoms.
• Hydrocarbon radical having 6 to 30 carbon atoms and in particular 7 to
• the hydrocarbon radical of the fatty acid is an unsubstituted AI kyl- or alkenyl radical.
• the hydrocarbon radical of the fatty acid bears one or more, for example two, three, four or more further substituents.
• the hydrocarbon radical of the fatty acid carries one, two, three, four or more further carboxyl groups.
• the hydrocarbon radical R 1 is an aromatic radical.
• aromatic carboxylic acids (I) are here in general, compounds which carry at least one carboxyl group bonded to an aromatic system.
• aromatic systems are cyclic, fürkonjugiert Systems with (4n + 2) ⁇ -electrons
• 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 made
• heteroatoms such as, for example, nitrogen, oxygen and / or sulfur.
• aromatic systems are benzene, naphthalene, phenanthrene, indole, furan, pyridine, pyrrole, thiophene and thiazole.
• 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, halogen atoms, alkyl and alkenyl radicals and also hydroxy, hydroxyalkyl, alkoxy, poly (alkoxy), amide, cyano and / or
• aryl radical carries at most as many substituents as it has valencies.
• the aryl radical preferably does not carry any amino groups.
• the aryl radical bears the aromatic
• Carboxylic acid (I) further carboxyl groups. So is the invention
• Process also suitable for the reaction of aromatic carboxylic acids with, for example, two or more carboxylic acid groups.
• Carboxylic acid groups can be completely or even partially converted into amides according to the inventive method.
• Amidierungsgrad can be, for example, by the stoichiometry between carboxylic acid and amino groups bearing organic acid in
• the process according to the invention is also particularly suitable for
• Alkylphenylcarbonklareamiden Process aromatic carboxylic acids (I), in which the aryl group carrying the carboxylic acid group additionally carries at least one alkyl or alkylene radical, reacted with amino acids bearing organic acids (II).
• the process is particularly advantageous for the preparation of Alkylbenzoeklareamiden, the aryl radical at least one alkyl radical having 1 to 20 carbon atoms and
• Carboxylic acids (I) are, for example, formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, pentanoic acid, iso-pentanoic acid, pivalic acid,
• Acrylic acid methacrylic acid, crotonic acid, 2,2-dimethylacrylic acid, maleic acid, fumaric acid, itaconic acid, cinnamic acid and methoxycinnamic acid, succinic acid, butanetetracarboxylic acid, phenylacetic acid, (2-bromophenyl) acetic acid,
• carboxylic acids or carboxylic acid mixtures are also suitable as carboxylic acids or carboxylic acid mixtures for the process according to the invention.
• tall oil fatty acid and also resin and naphthenic acids are also suitable as carboxylic acids (I) for example, benzoic acid, phthalic acid, isophthalic acid, the
• the at least one amino group bearing organic acid (II) carries
• acidic groups X are understood functional groups that can cleave at least one acidic proton.
• Acid groups which are preferred according to the invention X are carboxylic acids and organic acids of sulfur and phosphorus, for example sulfonic acids and phosphonic acids.
• the hydrocarbon radical A is preferably an aliphatic or aromatic radical with the proviso that A is not an acyl group or for a bonded via an acyl group to the nitrogen hydrocarbon radical.
• A is an aliphatic radical having 1 to 12 and more preferably having 2 to 6 carbon atoms. It can be linear, cyclic and / or branched. Preferably, it is saturated. A can be more
• Wear substituents are, for example, carboxylic acid amides, guanidine radicals, optionally substituted C 6 -C 2 -aryl radicals, for example indole and imidazole, and also acid groups, for example carboxylic acids and / or phosphonic acid groups.
• carboxylic acid amides for example, guanidine radicals, optionally substituted C 6 -C 2 -aryl radicals, for example indole and imidazole, and also acid groups, for example carboxylic acids and / or phosphonic acid groups.
• reaction in this case must be carried out with at most equimolar amounts of carboxylic acids (I) in order to avoid acylation of these OH groups.
• carboxylic acids (I) in order to avoid acylation of these OH groups.
• the aliphatic radical A carries the acid group X on the nitrogen atom ⁇ - or ß-standing carbon atom.
• the process according to the invention for the acylation of aliphatic acids carrying amino groups in which A is an alkyl radical having 1 to 12 carbon atoms and in which the acid group X is on the carbon atom which is ⁇ - or ⁇ -substituted is particularly useful and in particular of ⁇ -aminocarboxylic acids,
• A is an aromatic hydrocarbon radical having 5 to 12 C atoms.
• aromatic systems is meant here cyclic, fully conjugated (4n + 2) ⁇ -electron 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; it is preferably monocyclic.
• the aromatic radical A may contain one or more heteroatoms such as, for example, oxygen, nitrogen and / or sulfur. Amino and acid group this at least one
• Amino group bearing aromatic acid (II) may be ortho, meta as well as parastatician arranged on the aromatic system and in polynuclear aromatic systems are also located on different rings.
• suitable aromatic systems A are benzene, naphthalene, phenanthrene, indole, Furan, pyridine, pyrrole, thiophene and thiazole.
• the aromatic system A can carry one or more, for example one, two, three or more identical or different further substituents in addition to the carboxyl and amino group.
• Suitable further substituents are, for example, halogen atoms, alkyl and alkenyl radicals and hydroxyalkyl, alkoxy, poly (alkoxy), amide, cyano and / or nitrile groups. These substituents may be attached at any position of the aromatic system. However, the aryl radical carries at most as many substituents as it has valencies. In a preferred embodiment, R 2 is an aliphatic radical.
• the aliphatic radical may be linear, branched or cyclic. It may also be saturated or unsaturated, preferably it is saturated.
• the aliphatic radical may carry substituents such as halogen atoms, halogenated alkyl radicals, hydroxyl, C- ⁇ -C 5 alkoxyalkyl, cyano, nitrile, nitro and / or C 5 -C 2 o-aryl groups such as phenyl.
• C 5 -C 2 o-aryl radicals may in turn optionally be substituted by halogen atoms,
• halogenated alkyl groups hydroxyl, -C 2 o alkyl, C 2 -C 2O -AI kenyl-, C 1 -C 5 substituted -AIkOXy- such as methoxy, ester, amide, cyano, and / or nitrile be.
• Particularly preferred aliphatic radicals R 2 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 are especially preferred are methyl, ethyl, propyl and butyl.
• R 2 is an optionally substituted C 6 -C- 2 -aryl group or an optionally substituted
• R 2 is a further group of the formula -AX, where both A and X
• hydrocarbon radicals A and / or R 2 further acid groups such as for example, carry carboxyl and / or phosphonic acid groups are
• R 2 is hydrogen
• organic acids (II) carrying at least one amino group which are suitable according to the invention are amino acids such as glycine, alanine, arginine, asparagine, glutamine, histidine, leucine, isoleucine, valine, phenylalanine, serine, tyrosine,
• 3-aminopropionic acid ( ⁇ -alanine), 3-aminobutyric acid, 2-aminobenzoic acid, 4-aminobenzoic acid, 2-aminoethanesulfonic acid (taurine), N-methyltaurine,
• organic acid (II) bearing carboxylic acid (I) and amino group can be reacted with one another in any ratio.
• the reaction takes place between
• carboxylic acid (I) and amino group-bearing organic acid (II) are used equimolar with respect to the molar equivalents of carboxyl in (I) and amino groups in (II).
• carboxylic acid (I) 1 that is molar ratios of carboxyl to amino groups of at least 1, 01: 1, 00 and in particular between 50: 1 and 1, 02: 1 as for example between 10: 1 and 1, 1: 1 work.
• Volatile means that the carboxylic acid (I) 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.
• the preparation of the amides according to the invention is carried out by reacting carboxylic acid (I) and amino group-carrying organic acid (II)
• inorganic bases such as metal hydroxides, oxides, carbonates, silicates or alkoxides.
• metal hydroxides, oxides, carbonates, silicates or alkoxides particularly preferred are the hydroxides, oxides, carbonates, silicates or alkoxides of alkali or alkaline earth metals such as
• lithium hydroxide sodium hydroxide
• potassium hydroxide lithium hydroxide
• the conversion to the ammonium salt is carried out by adding a solution of the corresponding base, for example in a lower alcohol such as methanol, ethanol or propanol or in water to one of the reactants or the reaction mixture.
• a solution of the corresponding base for example in a lower alcohol such as methanol, ethanol or propanol or in water
• This procedure has proven particularly in the acylation of strong amines X carrying amines (II) such as sulfonic or phosphonic acid-bearing amines (II).
• Strong acids are understood here to mean, in particular, acids having a pKa of less than 3.5 and especially less than 3.0.
• the acceleration or Completion of the reaction worked in the presence of at least one catalyst.
• a basic catalyst Preferably, one works in the presence of a basic catalyst or mixtures of several of these catalysts.
• Basic catalysts which are generally used in the context of the present invention are those basic compounds which are suitable for accelerating the amidation of carboxylic acids with amines to carboxylic acid amides. These substances can be in solid form such as, for example, as a dispersion or fixed bed or as a solution such as, for example, as an aqueous or preferably as
• alcoholic solution can be used.
• suitable catalysts are inorganic and organic bases such as metal hydroxides, oxides, carbonates, silicates or alkoxides.
• the basic catalyst is selected from the group of hydroxides, oxides, carbonates, silicates or alkoxides of alkali or alkaline earth metals. Lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium methoxide,
• the amount of catalyst to be used can vary within wide limits. Often it has been proven to work with 0.1 to 2.0 moles of base such as 0.2 to 1, 0 moles of base per mole of amine used. Particular preference is given to using catalytic amounts of the abovementioned reaction-accelerating compounds, preferably in the range from 0.001 to 10% by weight, more preferably in the range from 0.01 to 5% by weight, for example from 0.02 to 2% by weight. -%, Based on the amount of carboxylic acid (I) and amino acid-bearing acid (II).
• the irradiation of the reaction mixture 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 acting as a microwave applicator waveguide is preferred as
• Cavity resonator formed. Further preferably, the microwaves not absorbed in the waveguide are reflected at its end. Preferably, the length of the cavity resonator is dimensioned so that it forms a standing wave in it.
• 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 in the direction of the central axis of symmetry of the
• Cavity resonator directed. It has a maximum in the area of the central axis of symmetry and decreases to the lateral surface to the value zero.
• Field configuration is rotationally symmetrical about the central axis of symmetry.
• n is an integer
• N is preferably an integer from 1 to 200, particularly preferably from 2 to 100, in particular from 3 to 50, especially from 4 to 20, for example three, four, five, six, seven, eight, nine or ten.
• TMoin mode The eoin mode of the cavity resonator is also referred to as TMoin mode in English, see, for example, K. Lange, K.H. Löcherer,
• the irradiation of the microwave energy in the as microwave applicator acting waveguide can be done via appropriately sized holes or slots.
• the irradiation of the reaction mixture with microwaves takes place in one
• Reaction tube located in a waveguide with coaxial transition of
• Microwave is located. Particularly preferred for this process
• Microwave devices are made of a cavity resonator, a
• 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 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.
• 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 one
• the cavity resonator preferably each has a central opening on two opposite end walls for passing the reaction tube.
• Coupling antenna acting 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.
• Reaction mixture with microwaves in a microwave transparent Reaction tube which is axially symmetrical in a Eoi n -Rundhohlleiter 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.
• the irradiation of the reaction mixture with microwaves in a microwave transparent reaction tube, the cavity resonator with n axial feed of the microwave is passed through a E 0 i the length of the is carried out,
• the irradiation of the reaction mixture with microwaves takes place in one
• Microwave transparent reaction tube which is passed through an EOM cavity resonator with axial feeding of the microwaves, wherein the length of the
• the irradiation of the reaction mixture with microwaves in a microwave-transparent reaction tube which is axially symmetrical in a circular cylindrical E 0 i n cavity resonator with coaxial transition of the microwaves is carried out, the length of the microwave-transparent reaction tube, which is axially symmetrical in a circular cylindrical E 0 i n cavity resonator with coaxial transition of the microwaves is carried out, the length of the microwave-transparent reaction tube, which is axially symmetrical in a circular cylindrical E 0 i n cavity resonator with coaxial transition of the microwaves is carried out, the length of the microwave-transparent reaction tube, which is axially symmetrical in a circular cylindrical E 0 i n cavity resonator with coaxial transition of the microwaves is carried out, the length of the microwave-transparent reaction tube, which is axially symmetrical in a circular cylindrical E 0 i n cavity resonator with coaxial transition of the microwaves is carried out, the length of
• 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 convert it into heat, the dielectric is often used
• Loss factor tan ⁇ ⁇ 'V ⁇ 'used.
• the dielectric loss factor tan ⁇ is defined as the ratio of dielectric loss ⁇ "and
• Dielectric constant ⁇ ' Dielectric constant ⁇ '.
• tan ⁇ values of various materials are given, for example, in D. Bogdal, Microwave Assisted Organic Synthesis, Elsevier 2005.
• materials having tan ⁇ 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.
• Preferred microwave-transparent and temperature-stable materials are primarily materials based on minerals such as quartz, alumina, sapphire, zirconium oxide, silicon nitride and the like into consideration.
• temperature-stable plastics such as in particular fluoropolymers such as Teflon, and engineering plastics such as polypropylene, or polyaryletherketones such
• PEEK glass fiber reinforced polyetheretherketone
• reaction tubes have an inner diameter of one millimeter to about 50 cm, in particular between 2 mm and 35 cm and especially between 5 mm and 15 cm as
• 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.
• Eor cavity resonators preferably have a diameter that is at least corresponds to half the wavelength of the microwave radiation used.
• the diameter of the cavity resonator is the 1, 0- to
• the Eor cavity resonator has a round cross-section, which is also referred to as an EorRundhohlleiter. 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.
• optionally catalyst can be carried out continuously, discontinuously or in semi-batch processes. So can the production of the
• Reaction mixture can be carried out in an upstream (semi) -batch process such as in a stirred tank.
• an upstream (semi) -batch process such as in a stirred tank.
• the catalyst can be added as such or as a mixture with one of the reactants to the reaction mixture.
• the educts and catalyst are fed to the process according to the invention in liquid form.
• higher melting and / or higher viscous starting materials for example in the molten state and / or with
• Solvent can be used, for example, as a solution, dispersion or emulsion.
• the catalyst is one of the educts or the
• reaction mixture before entering the reaction tube.
• heterogeneous Systems can be reacted by the process of the invention, with appropriate technical devices for conveying the reaction mixture are required.
• the reaction mixture 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 mixture can thus be guided parallel or antiparallel to the propagation direction of the microwaves by the microwave applicator.
• length of the irradiation zone (this is understood to mean the distance of the reaction tube in which the reaction mixture
• the reaction conditions are preferably adjusted so that the maximum
• Reaction temperature is reached as quickly as possible and the residence time at
• reaction mixture can be passed through the reaction tube several times to complete the reaction, optionally after intermediate cooling. At slower reactions, it has often proven that
• Reaction product immediately after leaving the reaction tube z. B. is cooled by jacket cooling or relaxation. It has also been proven to deactivate the catalyst immediately after leaving the reaction tube. This can be achieved, for example, by neutralization or by heterogeneously catalyzed
• the temperature increase caused by the microwave irradiation is, for example, regulated by controlling the microwave intensity
• Flow rate and / or by cooling the reaction tube for example, by a nitrogen stream, limited to a maximum of 500 0 C.
• the duration of microwave irradiation depends on various factors such as the geometry of the reaction tube, the irradiated
• 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.
• 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 preferably carried out at pressures between 1 bar (atmospheric pressure) and 500 bar, particularly preferably between 1.5 and 200 bar, in particular between 3 and 150 bar and especially between 10 and 100 bar, for example between 15 and 50 bar , It has proven particularly useful to work under elevated pressure, wherein above the boiling point (at atmospheric pressure) of the reactants, products, optionally present solvent and / or above the reaction water formed during the reaction is worked. 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.
• an inert protective gas such as nitrogen, argon or helium.
• Reaction conditions are inert 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 ⁇ . "The dielectric loss ⁇ " describes the proportion of
• Microwave radiation which in the interaction of a substance with
• Microwave radiation is converted into heat.
• the latter value has proved to be a particularly important criterion for the suitability of a solvent for the
• 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
• ⁇ dielectric loss
• solvents having ⁇ "values below 10 such as N-methylpyrrolidone, N, N-dimethylformamide or acetone, and in particular solvents having ⁇ " values below 1.
• solvents having ⁇ "values below 1 aromatic and / or aliphatic hydrocarbons such as 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 ⁇ "values preferably below 10 and especially below 1 are suitable for carrying out the process according to the invention
• the process according to the invention is carried out in solvents having higher ⁇ "values of, for example, 5 and higher, in particular ⁇ " values of 10 and higher, which in addition often show a superior dissolution behavior for the acids (II) carrying amino groups ,
• This embodiment has continued to be particularly in the
• Particularly preferred solvents are lower alcohols having 1 to 5 carbon atoms such as
• reaction mixture is preferably between 2 and 95 wt .-%, especially between 5 and 90 wt .-% and in particular between 10 and 75 wt .-% as
• reaction mixture in the insoluble, strongly microwave absorbing substances are added.
• Heat collector is graphite, for example.
• microwaves are electromagnetic radiation having a wavelength between about 1 cm and 1 m and frequencies between about 300 MHz and
• microwave radiation with the frequencies released for industrial, scientific, medical, domestic or similar applications is preferably used, for example with frequencies of 915 MHz, 2.45 GHz, 5.8 GHz or 24.12 GHz.
• Cavity resonator to be irradiated microwave power is particularly dependent on the desired reaction temperature, but also of the
• Geometry of the reaction tube and thus the reaction volume and the flow rate of the reaction mixture through the reaction tube 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.
• reaction is carried out in a pressure-resistant, chemically inert tube, wherein the water of reaction forming and optionally starting materials and, if present, solvent to a
• 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 after cooling and / or venting by conventional methods such as phase separation, filtration, distillation, stripping, flashing and / or absorption is separated.
• Reactor design according to the invention, the implementation of reactions even at very high pressures and / or temperatures.
• Microwave method of the prior art provides.
• 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, become known
• products according to the invention based on iron as the main element usually below 25 ppm, preferably below 15 ppm, especially below 10 ppm, such as between 0.01 and 5 ppm iron.
• the inventive method thus allows a very fast
• Carboxylic acid observed that would reduce the yield of target product. Such rapid and selective reactions can not be achieved by conventional methods and were not to be expected by heating to high temperatures alone.
• cylindrical cavity resonator (60 x 10 cm) was located. 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
• 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.
• Reaction mixture was directly after leaving the reaction zone (about 15 cm distance in an insulated stainless steel capillary, 0 1 cm) using PtIOO
• Temperature sensor made. Microwave energy not directly absorbed by the reaction mixture was reflected at the end face of the cavity resonator opposite the coupling antenna; the reaction mixture not absorbed in the return and in the direction of the magnetron
• Carboxylic acid and alcohol prepared reaction mixtures were pumped at a constant flow rate through the reaction tube and set the residence time in the irradiation zone by modifying the flow rate.
• the resulting mixture was pumped through the reaction tube at a working pressure of 35 bar continuously at 5 l / h and subjected to a microwave power of 2.2 kW, of which 94% were absorbed by the reaction mixture.
• the residence time of the reaction mixture in the irradiation zone was
• reaction mixture had a temperature of 255 0 C.
• reaction mixture had a temperature of 261 0 C.
• the reaction product contained ⁇ 5 ppm iron.
• the resulting mixture was pumped through the reaction tube continuously at 4 l / h at a working pressure of 35 bar and subjected to a microwave power of 2.6 kW, of which 90% was absorbed by the reaction mixture.
• the residence time of the reaction mixture in the irradiation zone was
• reaction mixture had a temperature of 267 0 C. It was a conversion of 79% d. Th. Reached.
• the reaction product contained ⁇ 5 ppm iron.
• the resulting mixture was pumped at a working pressure of 35 bar continuously at 3.5 l / h through the reaction tube and a microwave power of 1, 6 kW exposed, of which 87% were 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 281 0 C.
• the reaction product contained ⁇ 5 ppm iron.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Physics & Mathematics (AREA)
• Electromagnetism (AREA)
• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Toxicology (AREA)
• Clinical Laboratory Science (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Priority Applications (6)

Applications Claiming Priority (2)

Publications (2)

Family

ID=43128285

Family Applications (1)

Country Status (8)

Families Citing this family (22)

Family Cites Families (25)

• 2009
  • 2009-06-30 DE DE102009031056A patent/DE102009031056A1/de not_active Withdrawn
• 2010
  • 2010-06-09 CA CA2766933A patent/CA2766933A1/en not_active Abandoned
  • 2010-06-09 US US13/378,181 patent/US20120090983A1/en not_active Abandoned
  • 2010-06-09 EP EP10724308.1A patent/EP2448913B1/de not_active Not-in-force
  • 2010-06-09 WO PCT/EP2010/003444 patent/WO2011000461A2/de not_active Ceased
  • 2010-06-09 ES ES10724308T patent/ES2410632T3/es active Active
  • 2010-06-09 JP JP2012518032A patent/JP5851397B2/ja not_active Expired - Fee Related
  • 2010-06-09 KR KR1020127002479A patent/KR20120060199A/ko not_active Ceased

Non-Patent Citations (5)

Also Published As

Similar Documents

Legal Events