DE819992C - Process for the preparation of amides and thioamides - Google Patents

Description

Process for the preparation of amides and thioamides The invention relates to a process for the production of amides by modifying the Willgerodtschen Reaction, taking the place of the previously used ketones or other compounds an acetal is used as a starting material.

The production of amides from ketones by the oxidation of a ketone with aqueous ammonium polysulfide is in the art as Willgerodtsche. reaction known and was first described by him in 1887. After this reaction a ketone is heated with an aqueous solution of ammonium polysulfide, whereby an amide and the ammonium salt of the corresponding acid is obtained. It got later found that this reaction is also used to convert aldehydes to amides can be, and it has also been found that in place of ammonium polysulfide too a mixture of ammonium hydroxide and sulfur or optionally a primary one or secondary amine in a mixture with sulfur can be used as the starting material can. If an amine is used in the reaction, it is customary to use it in its absence of water, and the reaction product, if an amine is used, is not the amide, but the thioamide, but in the same way as the amide can be hydrolyzed and provides the corresponding acid.

It has now been found that unsubstituted and alkoxy-substituted Acetals despite their well-known stability in an alkaline medium according to Willgerodtschen Reaction can easily be converted into amides or thioamides, if only an unsubstituted or alkoxy-substituted one Acetal of the below named type in place of the ketone or the other previously used in the reaction Carbonyl compound is used.

The acetals that can be used in the practice of the present invention can be represented by the following general formula: In this, R denotes a hydrocarbon radical, ie alkyl, cycloalkyl, aryl or alkaryl, which, if R is an aliphatic hydrocarbon radical, can be substituted by one or more alkoxy groups, the number of alkoxy groups bonded to a single carbon atom being i, unless that said carbon atom is terminal as in the case of acetals of dialdehydes in which the number of alkoxy groups connected to the terminal carbon atom is two. The groups —O R1 mean the radical of an alcohol, and since the alcohol corresponding to the radical —O R1 and also the alcohol corresponding to any alkoxy substituents present on the group R when this is alkyl are split off during the reaction it is desirable from a practical standpoint that the -OR1 group be a lower alkoxy group. However, the process can also be carried out when acetals of higher alcohols are used. Examples of Aoetalen this kind, which present for carrying out the invention can be used are acetaldehyde, propionaldehyde dimethyl acetal, Butyraldehyddimethylacetal, Isobutyraldehyddimethylacetal, Valeraldehyddimethylacetal, Heptaldehyddimethylacetal, Lauraldehyddimethylacetal, Stearaldehyddimethylacetal, benzaldehyde dimethyl acetal, phenylacetaldehyde dimethylacetal, B-Phenylpropionaldehyddimethylacetal, Hexahydrobenzaldehyddimethylacetal and Malonaldehydtetramethylacetal, and the corresponding Diäthylacetale and Acetals of lower alcohols, such as the dibutyl acetals of the above-mentioned aldehydes, or the mixed acetals, such as methyl ethyl acetals from acetaldehyde and malonaldehyde triethyl methyl acetals. Some examples of alkoxy-substituted acetals of aliphatic aldehydes which can be used to practice the present invention are 1, 1, 3-trimethoxybutane, 1, 1, 3-trimethoxyhexane, i-methoxy-1, 3-diethoxyhexane, i, i, 3- Triethoxy-5, 5-dimethoxypentane, 1, 1, 3-triethoxy-5, 7, 7-trimethoxyheptane.

When ammonium polysulphide or a mixture of ammonium hydroxide and When sulfur is used as an oxidizing agent, the reaction will generally be carried out in an aqueous solution. If on the other hand, like Willgerodtschen Common reaction is a mixture of a primary or secondary amine and sulfur is used, the reaction is expediently carried out under anhydrous conditions. The amines that can be used in the practice of the present invention include primary and secondary alkyl, aryl and heterocyclic amines such as Methylamine, dimethylamine, ethylamine, diethylamine, dibutylamine, isopropylamine, morpholine, Piperidine, i- and 2-naphthylamine, aniline and methylaniline.

The reaction proceeds easily when there is a mixture of the starting materials is heated. Temperatures of about 125 to 23o ° have proven to be useful, and temperatures of 150 to 200 degrees seem to be the best. If the one or other or more of the starting materials are volatile at the reaction temperature the reaction is preferably carried out in a closed container under pressure carried out, but it can also be carried out under atmospheric pressure, if the special raw materials used remain liquid or at atmospheric Pressure can be refluxed. It has also been found to be beneficial although it is not necessary to use a solvent for the starting materials, such as dioxane, and especially when acetals have a relatively high molecular weight can be used as one of the reaction components.

The products obtained by the process of the present invention are amides of mono- or dibasic acids, depending on the particular acetal used. If unsubstituted acetals are used, the amide of the acid is obtained which corresponds to the aldehyde whose acetal has been used in the reaction, while in the case of acetals, alkoxy-substituted aliphatic aldehydes, in addition to the acetal substituents, also the alkoxy substituent or the alkoxy substituents are reduced so that when an acetal of an alkoxy-substituted aliphatic aldehyde is used, the amide of the acid is obtained which corresponds to the unsubstituted aldehyde having the same number of carbon atoms. Thus, in the case of using acetals of the above-mentioned alkoxy-substituted aldehydes, the following products are obtained Acetal amide der 1, 1, 3-trimethoxybutane butyric acid 1, 1, 3-trimethoxyhexane caproic acid 1, 3-diethoxy-i-methoxyhexane caproic acid i, i, 3-triethoxy-5, 5-dimethoxy- pentane glutaric acid i, i, 3-triethoxy-5, 7,; -trimetlioxv- heptane pimelic acid The invention is illustrated in more detail by the examples below. The parts are parts by weight. EXAMPLE i A mixture of 2 parts of butyraldehyde dimethyl acetal, 10 parts of dioxane and a solution of ammonium polysulphide, which was prepared by passing 10 parts of concentrated ammonium hydroxide and 1 part of sulfur, hydrogen sulphide through until the sulfur dissolved, was placed in a Carius tube. The tube was sealed and then heated to 160 ° for 12 hours. The reaction mixture, after taken out of the tube, was evaporated to dryness on a steam bath and then 20 parts of water was added to the residue. After the mixture was filtered to remove the unreacted sulfur, it was again evaporated to dryness and the butyramide was recrystallized from benzene to give crude butyramide in 80% yield. Another recrystallization from benzene gave a product with a melting point of 115 ° to 116 °.

Analysis: Calculated for C4H90N: C = 55i4%; H-io, 41 ° Jo; found: C = 55.099c '; H - 1o, 55%. Example e The same procedure was used as in Example i, but instead of the 2 parts of butyraldehyde dimethyl acetal, 3 parts of benzaldehyde dimethyl acetal were used and the product was recrystallized from water. A 75% yield of benzamide was obtained; Melting point 128 to 29 °.

Example 3 A mixture of 2 parts of butyraldehyde dimethyl acetal, 10 parts of concentrated ammonium hydroxide, 6 parts of sulfur and 10 parts of dioxane was placed in a Carius tube. After closing the reaction container, the mixture was heated to 160 ° for 12 hours. The reaction mixture was then removed from the tube and evaporated to dryness on a steam bath. Recrystallization of the reaction product from benzene gave a yield of butyramide of 64c / c; Melting point 114 to 115 °.

Example 4 If the procedure given in Example 3 is used, the butyraldehyde dimethyl acetal is replaced by 3 parts of benzaldehyde dimethyl acetal and If the product obtained is recrystallized from water, there is a yield of benzamide received by 63%; Melting point 125 to 127 °.

Example s A mixture of 76 parts of benzaldehyde dimethylacetal, 32 Parts of sulfur and 87 parts of morpholine were refluxed with stirring for 10 hours (125 to 14o °) heated. Hydrogen sulfide was evolved during the heating. The moist, solid residue that formed when the reaction mixture cooled, was recrystallized from ethyl alcohol, and there were 50 parts of 4-thiobenzoylmorpholine obtained with a melting point of 134-138 °.

Example 6 A mixture of 3 parts 1, 1, 3-trimethoxybutane, 10 parts Dioxane and an ammonium polysulphide solution which has been prepared by in 10 parts concentrated ammonium hydroxide and 1 part sulfur hydrogen sulfide until the sulfur was passed through, it was poured into a Carius tube. The tube was sealed and then heated to 160 ° for 12 hours. After taking it out from the tube the reaction mixture was evaporated to dryness on a steam bath, and 20 parts of water were added to the residue. After the mixture for the purpose Removal of the unreacted sulfur had been filtered it again evaporated to dryness and the butyrami-d recrystallized from benzene. The yield of butyramide was 80%, melting point 115 ° to 116 °. Example 7 a Mixture of 44 parts of i, i ', 3-triethoxy-5, 5'-dimethoxypentane, io parts of dioxane and an ammonium polysulfide solution prepared by dividing it into 220 parts concentrated ammonium hydroxide and 22 parts of sulfur hydrogen sulfide up to Solution of the sulfur passed through it was in a pressure vessel for 4 hours heated. The reaction mixture was thus evaporated to dryness, leaving crude glutaramide was obtained.

Claims (2)

PATENT CLAIMS: i. Process for the preparation of amides and thioamides, characterized in that an unsubstituted or alkoxy-substituted acetal, preferably an acetal containing the residues of lower alcohols, is reacted with an ammonium polysulfide or a mixture of sulfur and ammonium hydroxide or a primary or secondary amine. 2. The method according to claim i, characterized in that in the case of the preparation of thioamides under anhydrous Conditions an unsubstituted or alkoxy-substituted acetal with a mixture of sulfur and an amine is reacted with active amine hydrogen.