DE2953007C1 - Process for the preparation of carboxamides - Google Patents

Description

35

The invention relates to a process for the preparation of carboxamides by reacting at least a compound selected from the group consisting of primary alcohols and aldehydes with at least a compound selected from the group consisting of ammonia, primary amines, and secondary amines in the presence of a metal-containing oxidizing agent.

It is known that carboxamides, which are industrially valuable materials, by reaction of Carboxylic acids or their esters are made with an amine. This reaction or hydrolysis the corresponding nitriles can be used as a general process for the preparation of the carboxamides. the Yields of these reactions are almost satisfactory due to recent technical developments Height reached. However, these methods require long journeys from those serving as chemical raw materials Petroleum compounds. A solution for shortening these routes is, for example, in GB-PS 9 25 588 The process described is known in which N, N-dimethylformamide by reacting carbon oxide with Dimethylamine is produced, but this process requires high pressure and cumbersome operations for the treatment of by-products such as formic acid and other compounds. Hence became tried in the industry to develop a simpler and more economical process.

From DE-AS 15 93 470 a process for the production of acid amides from the corresponding Aldehydes or alcohols known, in which nickel peroxide in at least equimolar amount is used.

From Synthetic Methods of Organic Chemistry, page 179, a corresponding implementation is known in which Equimolar amounts of activated manganese dioxide can also be used for the oxidation. The manganese dioxide always has to be regenerated after the reaction.

The invention relates to a process for the preparation of carboxamides according to the above Claim 1. The subclaims relate to preferred embodiments of the method.

This process enables the simple and economical production of carboxamides.

The currently best embodiment for carrying out the method according to FIG Invention described.

One of the starting materials used in accordance with the process of the invention is a primary alcohol or an aldehyde. Suitable primary alcohols are, for example, monohydric alcohols, e.g. B. saturated aliphatic primary alcohols, e.g. B. methanol, ethanol, isopropyl alcohol, n-butyl alcohol, 2-ethylhexanol and n-octyl alcohol, unsaturated aliphatic primary alcohols, e.g. B. allyl alcohol and crotyl alcohol, aromatic alcohols, e.g. B. benzyl alcohol and cinnamyl alcohol, and heterocyclic alcohols, e.g. B. pyridyl alcohol and furfuryl alcohol. The above aromatic alcohols include the alcohols represented in the aromatic ring by a halogen atom, e.g. B. chlorine, bromine or fluorine, by a Ci-C ₅ -alkyl radical, for example methyl, ethyl, isopropyl or n-amyl, by a Ci-Cs-haloalkyl radical, for example chloromethyl or bromoethyl, or by an alkoxy radical, eg. B. methoxy or ethoxy, are substituted. The above-mentioned heterocyclic alcohols also include the alcohols in the hetero ring by a Ci-Cs-alkyl radical, for example methyl, ethyl, isopropyl or n-amyl, or by a Ci-Cs-haloalkyl radical, eg. B. chloromethyl or bromoethyl are substituted. Polyhydric alcohols, e.g. B. ethylene glycol, propylene glycol and glycerin can also be used.

Excellent in terms of reactivity in the method according to the invention are of these primary alcohols methyl alcohol, primary alcohols in which no hydrogen atom is attached to the carbon atom is bonded, which is adjacent to the carbon atom to which the alcoholic hydroxyl group is bonded, e.g. B. unsubstituted or substituted benzyl alcohol, unsubstituted or substituted pyridyl carbinols and unsubstituted or substituted furfuryl alcohol, primary alcohols with an unsaturated bond, the is bonded to the carbon atom which is adjacent to the carbon atom to which the alcoholic hydroxyl group is bonded is e.g. B. allyl alcohol and crotyl alcohol. Methyl alcohol, benzyl alcohol and pyridyl carbinol are particularly preferred and furfuryl alcohol.

Suitable aldehydes for the process of the invention are, for example, saturated aliphatic aldehydes, z. B. formaldehyde, acetaldehyde, propionaldehyde, pivalic acid aldehyde and caprylic aldehyde, unsaturated aliphatic aldehydes, e.g. B. acrolein and methacrolein, aromatic aldehydes, e.g. B. benzaldehyde, toluene aldehyde and cinnamaldehyde, heterocyclic aldehydes, e.g. B. furfural, pyridine aldehyde, thiophenaldehyde and pyrrole aldehyde. The above-mentioned aromatic aldehydes also include Aldeyhde im aromatic ring through a halogen atom, e.g. B. chlorine, bromine or fluorine, by a Ci-Cs-alkyl radical, e.g. Methyl, ethyl, isopropyl or n-amyl, by one

Ci - Cs-haloalkyl radical, ζ. B. chloromethyl or bromoethyl, or by an alkoxy radical, e.g. B. methoxy or ethoxy, are substituted.

The aforementioned heterocyclic aldehydes also include those in the heterocyclic Ring through a Ci-Cs-alkyl radical, e.g. Methyl, ethyl, isopropyl or n-amyl, or by a Ci -Q-haloalkyl radical, e.g. B. chloromethyl or bromoethyl, are substituted. Polyfunctional aldehydes, e.g. B. glyoxal and glutaric acid dialdehyde, can also ι ο be used.

Of these aldehydes, those mentioned below are excellent in reactivity to Process according to the invention: formaldehyde, aldehydes in which no hydrogen atom is attached to the Aldehyde group adjacent carbon atoms, d. H. the carbon atom in -position, is bonded, e.g. B. unsubstituted or substituted benzaldehydes, unsubstituted or substituted pyridine aldehydes and unsubstituted or substituted Furfurals, and aldehydes, in which there is an unsaturated bond with that of the aldehyde group adjacent carbon atom is bonded, z. B. Acrolein and Methacrolein. Formaldehyde is particularly preferred, Benzaldehyde, pyiridine aldehyde (picolinaldehyde, nicotinaldehyde and isonicotinaldehyde) and furfural.

The further starting material used in the process according to the invention is a primary one or secondary amine.

Typical examples of suitable primary amines are: aliphatic primary amines, e.g. B. Methylamine, ethylamine, propylamine, isopropylamine and butylamine; alicyclic primary amines, e.g. B. Cyclopentylamine and cyclohexylamine; aromatic primary amines, e.g. B. aniline, toluidines and naphthylamine; primary aralkylamines, e.g. B. benzylamine and xylidenediamine, and primary amines with a heterocyclic Scaffolding, e.g. B. a penicillin or cephalosporin. In addition to the primary amines mentioned, can any primary amine can be used.

Examples of suitable secondary amines are <to called: aliphatic secondary amines, e.g. B. dimethylamine, diethylamine, di-n-propylamine and methylethylamine; aromatic secondary amines, e.g. B. methylaniline and ethylaniline, and the compounds in which Nitrogen in a heterocyclic backbone forms the secondary amine structure, e.g. B. piperidine, piperazine, Pyrazoline, pyrrolidine and pyrroline. The aforementioned primary and secondary amines include Amines which are attached to a carbon atom building up the amine compound by a halogen atom, e.g. B. chlorine, bromine or Fluorine, by an alkali residue, e.g. B. methyl, ethyl, isopropyl or n-octyl, or by an alkoxy radical, z. B. methoxy or ethoxy, are substituted.

Particularly preferred of these amines are ammonia, the aforementioned primary amines, Dimethylamine, diethylamine, methylethylamine, piperidine and piperazine. The most suitable are ammonia, Methylamine, ethylamine, dimethylamine, diethylamine, etc.

The quantitative ratio of those selected from the stated primary alcohols and aldehydes Compound to the compound selected from ammonia and said primary and secondary amines is chosen at will depending on the reaction, but the molar ratio of & is 5 last-mentioned compound (ammonia or amine) to the first-mentioned compound (primary alcohol or Aldehyde) about 0.002 to 100 mol, preferably not less than 0.01 mol of the latter compound per mole of the former compound.

The oxygen used in the process of the invention is molecular oxygen, i. H. gaseous oxygen itself or a mixture of oxygen with a diluent gas which is inert in the reaction, e.g. B. gaseous nitrogen or gaseous carbon dioxide is used. Air can also be used. The oxygen becomes in the reaction system in not less than that required for the reaction stoichiometric amount, preferably used in not less than 1.5 times the sufficient amount.

Palladium or platinum is used as the catalyst in the process of the invention. These metals can are used alone, but are preferably in a form coated on a carrier used. Usual carriers, e.g. B. activated carbon, silicon dioxide or aluminum oxide, can without difficulty be used. The amount of metal coated on this support can range from about 0.1 to 20% by weight and is preferably about 0.5 to 10% by weight.

Further, when at least one metal selected from the group consisting of lead, thallium and mercury is included in the Palladium or platinum catalyst is incorporated, will give better results than when used alone obtained from metallic palladium or metallic platinum. The lead, thallium or mercury can can be used in the form of the metal or a metal compound. As connections, for example the salts of lead, thallium or mercury, e.g. B. the halides, the salts with inorganic ones Acids or the salts with organic acids as well as the oxides and hydroxides can be used. As halides the chlorides, bromides, iodides and fluorides are suitable. Suitable as salts with inorganic acids salts with sulfuric acid, nitric acid, phosphoric acid and boric acid. As salts with organic acids come salts with formic acid, acetic acid, propionic acid, stearic acid, malonic acid, succinic acid, glutaric acid, Maleic acid, benzoic acid, phthalic acid and other acids in question. The lead, or thallium Mercury is added to the palladium or platinum catalyst in an amount of from about 0.01 to about 30, preferably 0.1 to 10, calculated as the atomic ratio of the former to the latter, is added.

The palladium or platinum catalyst can be prepared by conventional methods. For use in the reaction, the production can take place, for example, as follows: A carrier material is converted into a aqueous solution of a salt of palladium or platinum dipped, dried and mixed with hydrogen, hydrazine or formalin reduced to the metallic state.

The above-mentioned catalyst containing lead, thallium or mercury can also be used in conventional Ways to be prepared, for example, as follows: A carrier is an aqueous solution of lead acetate added. The mixture is stirred for a few hours so that the lead acetate can be adsorbed and the The mass obtained is calcined at about 500 to 700.degree. The product obtained is then a aqueous solution of palladium chloride added, followed by stirring for a few hours so that the Adsorption of the palladium chloride takes place, whereupon the resulting mass of the reduction treatment with Formalin, hydrazine or hydrogen is subjected. In the case of the catalyst system, the platinum and a Containing lead salt, the catalyst can be produced

are by adding a carrier for the platinum to an aqueous solution of a lead salt, the mixture is stirred and then dried.

If lead, thallium or mercury is used in combination, it is preferably also set to ί applied to a carrier. An amount of palladium or platinum applied to the carrier is favorable about 0.1 to 20% by weight, based on the carrier, with an amount in the range from about 0.5 to 10% by weight is particularly cheap. Compared to platinum, ι ο palladium leads both when used alone and in the system in which it is used in combination with lead, thallium or mercury Results.

The reaction temperature in the process according to ι5 Invention is in the range of 0 ° to 200 ° C. The reaction can take place at a relatively low temperature from about 15 to 150 ° C. It is surprising that such responsiveness of the Oxidation occurs near ordinary temperature.

It is also possible to use an inert solvent, e.g. B. dimethylformamide or dioxane, to use the Solubilize starting materials. The reaction can be carried out under any pressure (reduced pressure, Normal pressure or positive pressure). It can also be carried out batchwise or continuously be performed.

The process of the invention is further illustrated by the following examples.

example 1

10 ml a 40 weight percent aqueous dimethylamine solution, 100 ml of methanol and 5 g of a commercially available one available 5% palladium carbon (manufacturer Engelhard Corp.) given as a catalyst. The temperature in Feces increased to 40 ° C. With good stirring of the reaction liquid, air passed through the gas inlet in an amount of 151 / hour Initiated 2 hours to carry out the reaction.

Analysis of the reaction solution after the reaction had ended showed that the conversion of dimethylamine 92% and the yield of N, N-dimethylformamide based on the dimethylamine used was 78%.

Example 2

Using the reaction apparatus described in Example 1, 50 ml of an aqueous so Solution, the 5 g of 3-hydroxymethyl-pyridine, which belongs to the pyridyla alcohols, and 2 g of a commercially available one available 5% palladium carbon (manufacturer Engelhard Corp.) given as a catalyst, whereupon the Temperature was increased to 50 ° C. The reaction was carried out by pouring ammonia gas into an amount of 0.3 1 / hour. and air at 101 / hr. 3 hours were initiated. The analysis gas chromatography gave a yield of 62% nicotinamide, based on the 3-hydroxy-fco used methyl pyridine. No other products were detected.

Example 3

In the reaction apparatus described in Example 1 ^ 10 40gewichtsprozentigen an aqueous dimethylamine solution, 100 ml of ethanol and 5 g of commercial 5% palladium carbon (manufactured by Engelhard Corp.) were added as catalyst, ml, was increased and the temperature at 50 ° C. The mixture was left to react for 4 hours by adding oxygen in an amount of 2 liters / hour. was introduced.

Analysis of the solution of the reaction mixture after the reaction indicated a yield of N.N-dimethylacetamide of 23%, based on the dimethylamine used.

Example 4

2 g of pyridine-3-aldehyde, 50 g of aqueous ammonia (28%) and 2 g of commercially available 5% palladium carbon (Manufactured by Engelhard Corp.) as a catalyst were placed in a 100 ml three-necked flask. The reaction was carried out for 2 hours at 40 ° C, while oxygen through a gas inlet tube provided with a filter was introduced.

Analysis by gas chromatography after the reaction indicated a conversion of pyridine-3-aldehyde of 67% and a nicotinamide yield of 57%.

Example 5

Using the apparatus described in Example 4, 2 g of benzaldehyde, 60 g of dioxane were used as Solvent and 3 g of commercially available 5% palladium carbon (manufacturer Engelhard Corp.) in the flask given. The temperature was adjusted to 50 ° C and the reaction by introducing gaseous Ammonia in an amount of 1 liter / hour. and air at 101 / hr. performed for 3 hours, wherein Benzamide was obtained in a yield of 49%, based on the benzaldehyde used.

Example 6

2 g of pyridine-3-aldehyde, 60 g of an aqueous (40%) solution of dimethylamine and 2 g of commercially available 5% Palladium-aluminum oxide (manufactured by Engelhard Corp.) as a catalyst was allowed to react in the for 3 hours the same apparatus as in Example 1 at a reaction temperature of 50 ° C subjected by Oxygen in an amount of 5 liters / hour. was introduced.

The conversion of pyridine-3-aldehyde was 79% and the yield of nicotine dimethylamide was 62%.

Example 7

2 g of tetraoxane, a formaldehyde-yielding compound, 60 g of an aqueous (40%) solution of Dimethylamine and 3 g of commercially available 5% palladium-aluminum oxide (manufacturer Engelhard Corp.) as a catalyst were 3 hours of reaction using the same apparatus as in Example 1 at a Subjected to reaction temperature of 40 ° C by adding oxygen in an amount of 6 1 / hour. was introduced. The yield of Ν, Ν-dimethylformamide was 61%.

Example 8

2 g of pyridine-3-aldehyde, 50 g of aqueous ammonia (28%) and 3 g of an activated carbon containing as a carrier Catalyst (applied palladium 5%, Pd / Pb atomic ratio 1: 3, Pb applied in the form of PbO) were placed in a 100 ml three-necked flask and reacted in the manner described in Example 1, the following results were obtained:

Conversion of pyridine-3-aldehyde 81%

Yield of nicotinamide 77%

Example 9 Example 14

Using the same apparatus as in Example 1, 2 g of benzaldehyde, 50 g of dioxane as a solvent and 2 g of a catalyst containing aluminum oxide as a support (applied palladium 8%, Pb / Tl atomic ratio = 1: 0.1, Tl were in the form of of TlNO ₃ applied) 2 hours of reaction by introducing ammonia in an amount of 1 1 / hour. and oxygen in an amount of 101 / hour. carried out while the temperature was kept at 40 ^° C. Benzamide was obtained in a yield of 71%.

Example 10

I) 2 g of pyridine-3-aldehyde and 30 g of aqueous ammonia (28%) were treated with 5 g of a catalyst containing aluminum oxide as a support (content of applied palladium 3%; Pd / Pb atomic ratio = 1: 2; Pb in the form of a mixture of Pb and PbO in a weight ratio of Pb / PbO of 1: 2) were placed in a 100 ml three-necked flask. The reaction was carried out in the manner described in Example 1, with the following results being obtained:

Conversion of pyridine-3-aldehyde 77%

Yield of nicotinamide 74%

2 g of benzyl alcohol, 40 g of dioxane as a solvent, 20% aqueous ammonia (28%) and 2 g of one Catalyst containing activated carbon as carrier (content of applied palladium 5%; Pd / Pb atomic ratio =! : 3; Pb applied in the form of PbO) were placed in a 100 ml three-necked flask and reacted in the manner described in Example 1, the following results being obtained:

Sales of benzyl alcohol
Yield of benzamide

Example 11

75% 65%

25th

30th

In the same apparatus as in Example 1, 2 g of furfural and 60 g of dioxane were combined as solvents with 2 g of commercially available 5% palladium carbon (manufacturer Engelhard Corp.). The reaction became 2 Hours carried out at a temperature of 50 ° C, 3> by adding gaseous ammonia in an amount of 1 l / h. and oxygen in an amount of 101 / hour. were introduced. Here, furfurylamide was used in a yield of 51%, based on the furfural used, obtain.

Example 12

4 g of benzyl 6-aminopenicillanate and 60 g of methanol were combined with 4 g of a catalyst containing aluminum oxide as a support (applied palladium ->■>4%; Pd / Pb atomic ratio 1: 5; Pb applied in the form of PbO) were in a 100 ml three-necked flask. With thorough stirring of the liquid reaction mixture while maintaining an internal temperature of 30 ⁰ C air was 2 hours in an amount><> of 101 / hour. introduced through the gas inlet. Benzyl 6-N-formylpenicillanate was obtained in a yield of 14%.

Example 13

55

Using the same apparatus as in Example 1, 2 g of pyridine-3-aldehyde and 60 g of an aqueous (40%) solution of dimethylamine together with 2 g of a catalyst containing activated carbon as a support (content of applied palladium 4%; Pd / Hg atomic ratio 1: 0, l; Hg in the form of HgCl ₂ applied implemented) for 2 hours at a reaction temperature of 40 ⁰ C by oxygen in an amount of 61 / hr. was introduced. The following results were obtained:

Conversion of pyridine-3-aldehyde 81%

Yield of nicotine dimethylamide 75%

Example 15

2 g of methacrolein, 20 g of an aqueous 40% strength dimethylamine solution and 30 g as solvent were placed in the same apparatus as in Example 1 together with 3 g of commercially available 5% platinum activated carbon. The reaction was stopped for 1 hour by introducing oxygen in an amount of 4 liters per hour. carried out while the temperature was kept at 30 ^° C. Methacryldimethylamide was obtained in a yield of 19%, based on methacrolein.

Example 16

Using the same apparatus as in Example 1, 2 g of furfuryl alcohol, 30 g of an aqueous 40% methylamine solution, 20 g of dioxane as a solvent and 4 g of a catalyst containing activated carbon as a carrier (content of applied palladium 5%; Pd / Pb atomic ratio = 1: 3; Pb applied in the form of lead acetate) were ^{reacted for 2 hours at a reaction temperature of 40 0} C, while oxygen in an amount of 5 1 / hour. was introduced. The following results were obtained:

Conversion of furfuryl alcohol 77%

Yield of furfuryl monomethylamide 69%

Example 17

Using the same apparatus as in Example 1, 2 g of pyridine-3-aldehyde, 5 g of benzylamine, 40 g of dimethylformamide as a solvent and 3 g of a catalyst containing aluminum oxide as a support (Content of applied platinum 5%; Pt / Pb atomic ratio = 1: 1; Pd applied in the form of lead hydroxide) Reacted for 2 hours at a reaction temperature of 25 ° C. by adding air in an amount of 6 1 / hour. was introduced. Nicotinbenzylamide was obtained in a yield of 23%.

Example 18

Using the same apparatus as in Example 1, 2 g of crotyl alcohol, 30 g of an aqueous 40% methylamine solution, 30 g of dioxane as a solvent and 3 g of a catalyst containing activated carbon as a carrier (content of platinum applied 5%; Pt / Pb atomic ratio = 1: 0.5; Pb applied in the form of lead bromide) ^{reacted for 1 hour at a reaction temperature of 30 °} C. by adding oxygen in an amount of 5 1 / hour. was introduced. Methacrylmonomethylamide was obtained in a yield of 31%.

Example 19

2 g of pyridine-3-aldehyde, 50 g of a 30% aqueous Äthylaminlösung and 3 g of commercial 5% palladium carbon (manufactured by Engelhard Corp.) as a catalyst ^r> were placed in a 100-ml three-necked flask. The reaction was carried out for 2 hours at 30 ^° C., while oxygen was passed through a gas inlet connection provided with a filter in an amount of 101 / hour. was introduced. Nicotinmonoäthyl- ι ο amide was obtained in a yield of 47%.

B e i s ρ i e 1 20

5 g of diethylamine, 50 g of methanol and 5 g of a catalyst containing activated carbon as a carrier (content of applied palladium 10%; Pd / Pb atomic ratio = 1:10; Pb applied in the form of lead nitrate) were placed in a 100 ml three-necked flask . With thorough stirring of the liquid reaction mixture and maintaining an internal temperature of the flask of 40 ⁰ C, the reaction was carried out for 3 hours by adding oxygen in an amount of 5 1 / hour. was introduced. Diethylformamide was obtained in a yield of 59%, based on the diethylamine used.

Example 21

2 g of piperidine, 50 g of methanol and 4 g of a catalyst containing aluminum oxide as a support (content of applied palladium 5%; Pd / Pb atom behaves- Jo nis = 1: 1; Pb applied in the form of PbO) were in placed in a 100 ml three-necked flask. With good stirring, the liquid reaction mixture was 2 hours while maintaining an internal temperature of the flask of 45 ° C implemented by oxygen in a Amount of 101 / hour was introduced through the gas inlet. Here were N-formylpiperidine in a Yield of 41% and N, N-diformylpiperidine in a yield of 7%, based on the piperidine used, obtain.

Example 22

2 g benzyl 7-aminocephalosporanate, 10 g benzaldehyde, 50 g of dimethylformamide as a solvent and 3 g of a catalyst containing silicon dioxide as a support (Platinum applied content 5%) was placed in a 100 ml three-necked flask. Under good Stir the liquid reaction mixture and maintain an internal temperature of the flask at 25 ° C the reaction was carried out for 2 hours by passing oxygen through the gas inlet in an amount of 5 1 / hour was introduced.

The yield of benzyl N-benzoyl cephalosporanate was 12% based on benzyl-7-aminocephaIosporanat.

According to the process of the invention, carboxamides can be obtained in good yields under mild ones Conditions and in a one-step synthesis process from aldehydes and amines or from alcohols and amines. This method is therefore extremely advantageous economically.

The superiority of the process compared to the state of the art can be seen from the following test report:

Test report

Example 4 of the present application was repeated, but instead of 2 g palladium carbon 0.1 g of nickel peroxide was used. In this way there were 16.0% pyridine-3-aldehyde and 4% nicotinamide obtain.

Example 4 was repeated again, but 0.1 g of nickel was used instead of the palladium-carbon used. In this way, 13% pyridine-3-aldehyde and 0.3% nicotinamide were obtained.

Example 4 was repeated again, but 0.1 g of manganese dioxide was used instead of palladium-carbon and 0.9 g of sodium cyanide was used. In this way, 11.4% pyridine-3-aldehyde and 2.1% Nicotinamide.

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Claims (4)

Patent claims: 1. Process for the preparation of carboxamides by reacting at least one compound from the group consisting of primary alcohols and aldehydes with at least one compound from the group consisting of ammonia, primary amines and secondary amines in the presence of a metal-containing oxidizing agent, characterized in that the reaction takes place at a temperature of 0 to 200 ^° C. in the presence of a gas containing molecular oxygen and a palladium or platinum catalyst optionally containing lead, thallium and / or mercury. 2. The method according to claim 1, characterized in that the reaction is carried out in the presence a catalyst carried out, the applied to a support metallic palladium or metallic Contains platinum. 3. The method according to claim 1 or 2, characterized in that the reaction is carried out in the presence carries out a supported catalyst, on which about 0.1 to 20 wt .-% palladium or platinum, based on the carrier, are applied. 4. The method according to any one of claims 1 to 3, characterized in that the reaction in Carries out the presence of a catalyst which has an atomic weight ratio of lead, thallium or Has mercury to palladium or platinum from 0.01 to 30.