JP6566546B2 - Method for producing amide compound - Google Patents

Description

  The present invention relates to a method for producing an amide compound, and more particularly to a method for producing an amide compound by subjecting an oxime compound to a Beckmann rearrangement reaction.

  The conversion reaction of the oxime compound into the amide compound by the Beckmann rearrangement is a 100% “atom economy” reaction in which the types and numbers of elements constituting the starting material and the target product are exactly the same. As an industrial amide compound production method, a method of producing ε-caprolactam by Beckmann rearrangement of cyclohexanone oxime using a strong acid such as concentrated sulfuric acid or fuming sulfuric acid in a liquid phase is well known. In this method, in order to form a salt with the strong acid added by the produced lactam, the strong acid is usually used in excess. Accordingly, since an aqueous ammonia solution is used in the neutralization step when separating ε-caprolactam from the reaction product solution, there is a problem that a large amount of ammonium sulfate is by-produced.

  In order to solve the above problems, the present inventors, when used alone, have a catalytic amount (about 10 mol%) of a cobalt salt or nickel salt having a low activity, a Lewis acid having a catalytic amount of 10 to 20 mol%, It has been found that by using in combination with Bronsted acid, acid anhydride, acid chloride or the like, it is possible to produce an amide compound with high selectivity by suppressing the formation of by-products. In this method, in order to take out the produced amide compound most efficiently, it is preferable to perform a base treatment in the same manner as in the conventional method, but the inorganic salt produced as a by-product by the base treatment is reduced to 1/5 to 1/3 or less. It can be reduced (Patent Documents 1 to 4).

  In addition, various studies have been made on the catalyst used in the Beckmann rearrangement reaction. For example, a catalyst (non-patent document 1) consisting of an ion pair (Vilsmeier complex) generated from N, N-dimethylformamide and chlorosulfonic acid, an alkylation generated from an epoxy compound and a strong acid (such as boron trifluoride / etherate) And a catalyst comprising N, N-dialkylformamide (Non-patent Document 2), a catalyst comprising phosphoric acid or a condensable phosphoric acid compound (Patent Document 5), a compound such as N, N-dialkylformamide, phosphorus pentoxide, In addition, a catalyst such as a catalyst comprising a strong fluorine-containing acid or a derivative thereof (Patent Document 6), indium triflate (Non-Patent Document 3), ytterbium triflate (Non-Patent Document 4), and the like are known.

JP 2011-178672-A JP 2011-190207 A JP 2011-173814 A JP 2011-184332 A Japanese Patent Laid-Open No. Sho 62-149665 JP-A-5-105654

M.M. A. Kira and Y.K. M.M. Shaker, Egypt. J. et al. Chem. 16,551 (1973) Y. Izumi, Chemistry Letters, p. 2171 (1990) J. et al. S. Sandhu, et. al. , Indian Journal of Chemistry, pp. 154-156 (2002) J. et al. S. Yadav, et. al. , Journal of Chemical Research (S), pp. 236-238 (2002)

  However, these methods are not preferable for industrial use because of the use of an unstable catalyst in the air or the use of a catalyst that generates a corrosive gas by decomposition. Moreover, base treatment is still necessary, and the by-product of inorganic salt cannot be avoided. Therefore, it is desired to develop a method for producing an amide compound with high selectivity by suppressing the formation of by-products using a catalyst that is easy to handle.

  The present invention has been made in view of the above problems, and in a method for producing an amide compound by subjecting an oxime compound to a Beckmann rearrangement reaction, the formation of a by-product is suppressed and the amide has a high selectivity. It aims at providing the manufacturing method of the amide compound which can manufacture a compound.

  In order to achieve the above object, the present inventors have conducted extensive research, and as a result, Beckmann rearrangement reaction is carried out in the presence of a catalyst composed of the following (A) to (C) to produce a by-product. The inventors have found that an amide compound can be produced with high selectivity while suppressing the above, and have led to the present invention.

  That is, the present invention provides a method for producing an amide compound by subjecting an oxime compound to a Beckmann rearrangement reaction, wherein (A) any one or more of a cobalt salt and a nickel salt, and (B) any of a magnesium salt and a sodium salt. The present invention relates to a method for producing an amide compound, characterized by carrying out a Beckmann rearrangement reaction in the presence of a catalyst composed of one or more and (C) silica gel.

  ADVANTAGE OF THE INVENTION According to this invention, the production method of the amide compound which can suppress the production | generation of a by-product and can manufacture an amide compound with high selectivity can be provided. Further, after the reaction, the product can be isolated only by filtration without performing a base treatment, and a method for producing an amide compound which does not produce an inorganic salt as a by-product can be provided.

(Oxime compounds)
The oxime compound used in the present invention is not particularly limited and can be appropriately selected depending on the amide compound to be produced. As an oxime compound, the compound represented by following formula (1) is mentioned, for example.

In formula (1), R ¹ and R ² each represents an organic group. R ¹ and R ² may be a divalent organic group bonded to each other to form a ring.

Examples of the organic group in R ¹ and R ² include alkyl groups, alkenyl groups, alkynyl groups, cycloalkyl groups, cycloalkenyl groups, aryl groups, aralkyl groups, and heterocyclic groups.

  As an alkyl group, a C1-C20 alkyl group is mentioned, for example, It is preferable that it is a C1-C12 alkyl group, and it is more preferable that it is a C2-C8 alkyl group. . Specific examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, isopentyl, hexyl, isohexyl, and heptyl. Group, octyl group, nonyl group, decyl group, dodecyl group, pentadecyl group and the like.

  Examples of the alkenyl group include alkenyl groups having 2 to 20 carbon atoms, preferably alkenyl groups having 2 to 12 carbon atoms, and more preferably alkenyl groups having 2 to 8 carbon atoms. . Specific examples of the alkenyl group include a vinyl group, an allyl group, a 1-propenyl group, a 1-butenyl group, a 1-pentenyl group, and a 1-octenyl group.

  Examples of the alkynyl group include alkynyl groups having 2 to 20 carbon atoms, preferably alkynyl groups having 2 to 12 carbon atoms, and more preferably alkynyl groups having 2 to 8 carbon atoms. . Specific examples of the alkynyl group include ethynyl group and 1-propynyl group.

  Examples of the cycloalkyl group include a cycloalkyl group having 3 to 20 carbon atoms, and a cycloalkyl group having 3 to 15 carbon atoms is preferable. Specific examples of the cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, and a cyclododecyl group.

  As a cycloalkenyl group, a C3-C20 cycloalkenyl group is mentioned, for example, It is preferable that it is a C3-C15 cycloalkenyl group. Specific examples of the cycloalkenyl group include a cyclopentenyl group, a cyclohexenyl group, and a cyclooctenyl group.

  As an aryl group, a C6-C24 aryl group is mentioned, for example. Specific examples of the aryl group include a phenyl group and a naphthyl group.

  Examples of the aralkyl group include aralkyl groups having 7 to 25 carbon atoms. Specific examples of the aralkyl group include a benzyl group, a 2-phenylethyl group, and a 3-phenylpropyl group.

  As a heterocyclic group, an aromatic heterocyclic group and a non-aromatic heterocyclic group are mentioned, for example, It is preferable that it is a C1-C24 heterocyclic group. Specific examples of the heterocyclic group include a 2-pyridyl group, a 2-quinolyl group, a 2-furyl group, a 2-thienyl group, and a 4-piperidinyl group.

When R ¹ and R ² are an organic group bonded to each other to form a ring, examples of the divalent organic group include a linear or branched alkylene group, and a linear alkylene group is preferable. . The alkylene group preferably includes a 3- to 30-membered ring including the carbon atom of the oxime compound represented by the formula (1), more preferably a 4- to 20-membered ring, It is particularly preferable that a 5- to 14-membered ring is formed. Specific examples of the divalent alkylene group include an ethylene group, a trimethylene group, and a propylene group.

  The organic group is not particularly limited as long as it does not inhibit the Beckmann rearrangement reaction, and may have various substituents. Examples of the substituent include a halogen atom, oxo group, mercapto group, alkoxy group, aryloxy group, acyloxy group, alkylthio group, arylthio group, heteroarylthio group, oxycarbonyl group, carbamoyl group, cyano group, nitro group, Examples include aminoalkyl groups, alkenyl groups, alkynyl groups, cycloalkyl groups, cycloalkenyl groups, aryl groups, heteroaryl groups, aralkyl groups, and heterocyclic groups.

In formula (1), examples of the oxime compound in which R ¹ and R ² are each an organic group include acetone oxime, 2-butanone oxime, 2-pentanone oxime, 3-pentanone oxime, and 1-cyclohexyl-1 -Propanone oxime, acetophenone oxime, p-methoxyacetophenone oxime, o-methoxyacetophenone oxime, p-fluoroacetophenone oxime, benzophenone oxime, and 4-hydroxyacetophenone oxime. Examples of the oxime compound in which R ¹ and R ^{2 in} formula (1) are divalent organic groups bonded to each other to form a ring include, for example, cyclopropanone oxime, cyclobutanone oxime, cyclohexanone oxime, cycloheptanone Oxime, cyclooctanone oxime, cyclononanone oxime, cyclodecanone oxime, cyclododecanone oxime, cyclotridecanone oxime, cyclotetradecanone oxime, cyclopentadecanone oxime, cyclohexadecanone oxime, cyclooctadecanone oxime, And cyclononadecanone oxime. Among these oxime compounds, cyclododecanone oxime, cyclohexanone oxime, acetophenone oxime, p-methoxyacetophenone oxime, o-methoxyacetophenone oxime, and p-fluoroacetophenone oxime are preferable, and cyclododecanone oxime or cyclohexanone oxime is preferable. More preferably it is. One or more oxime compounds can be selected and used.

  The oxime compound can be obtained by reacting a ketone corresponding to the oxime compound represented by the formula (1) with hydroxylamine. The oxime compound is an N-hydroxyimide compound derived from an aliphatic polyvalent carboxylic acid anhydride or an aromatic polyvalent carboxylic acid anhydride, or a protective group (for example, acetyl group) on the hydroxyl group of the N-hydroxyimide compound. It can also be obtained by reacting a compound having a methyl group or a methylene group with a nitrite or nitrite in the presence of a compound obtained by introducing an acyl group such as a group. Examples of the aliphatic polycarboxylic anhydride or aromatic polycarboxylic anhydride include N-hydroxysuccinimide, N-hydroxyphthalimide, N, N′-dihydroxypyromellitic diimide, and N-hydroxy. Examples include glutarimide, N-hydroxy-1,8-naphthalenedicarboxylic acid imide, and N, N′-dihydroxy-1,3,4,5-naphthalenetetracarboxylic acid diimide (for example, JP 2009-298706 A). Issue gazette).

((A) one or more of cobalt salt and nickel salt)
Examples of the cobalt salt used in the present invention include inorganic compounds such as cobalt oxide, cobalt chloride, cobalt bromide, cobalt nitrate, cobalt sulfate, cobalt phosphate, cobalt perchlorate, and cobalt tetrafluoroborate; cobalt acetate, Examples include organic acid salts such as cobalt naphthenate and cobalt stearate; cobalt compounds of complexes such as cobalt acetylacetonate, and the hydrates thereof. The hydrate is preferably cobalt nitrate hexahydrate, cobalt perchlorate hexahydrate, or cobalt tetrafluoroborate hexahydrate, and is cobalt tetrafluoroborate hexahydrate. Is particularly preferred. Commercial products can be used for these.

  Examples of the nickel salt used in the present invention include inorganic compounds such as nickel oxide, nickel chloride, nickel bromide, nickel nitrate, nickel sulfate, nickel phosphate, nickel perchlorate and nickel tetrafluoroborate; Examples thereof include organic acid salts such as nickel, nickel naphthenate and nickel stearate; nickel compounds of complexes such as nickel acetylacetonate and the like, and hydrates thereof. The hydrate is preferably nickel nitrate hexahydrate, nickel sulfate hexahydrate, nickel perchlorate hexahydrate, nickel tetrafluoroborate hexahydrate, nickel tetrafluoroborate Hexahydrate is particularly preferred. Commercial products can be used for these.

  The amount of cobalt salt and nickel salt used is preferably 0.1 to 100 mol%, more preferably 1.0 to 50 mol% of the oxime compound.

(One or more of (B) magnesium salt and sodium salt)
Examples of the magnesium salt used in the present invention include magnesium nitrate, magnesium sulfate, magnesium chloride, magnesium bromide, magnesium iodide, and hydrates thereof. Examples of the hydrate include magnesium nitrate hexahydrate, magnesium chloride hexahydrate, magnesium sulfate heptahydrate and the like. The magnesium salt is particularly preferably magnesium sulfate, magnesium chloride, or magnesium nitrate hexahydrate. Commercial products can be used for these.

  Examples of the sodium salt used in the present invention include sodium hydrogen sulfate, sodium sulfate, sodium hydrogen carbonate, sodium carbonate, sodium chloride, sodium bromide, sodium iodide and the like. The sodium salt is particularly preferably sodium hydrogen sulfate, sodium sulfate, sodium hydrogen carbonate or sodium carbonate. Commercial products can be used for these.

  The amount of magnesium salt and sodium salt used is preferably 0.1 to 100 mol%, more preferably 5.0 to 60 mol% of the oxime compound.

((C) Silica gel)
In the present invention, a commercially available silica gel can be used, and is not particularly limited, but those having a particle diameter of 500 μm or less are preferable. The shape of the silica gel includes a crushed shape and a spherical shape, but is not particularly limited.

  The amount of silica gel used is preferably 0.1 mol% or more of the oxime compound, but if it is too much, stirring tends to be difficult, and more preferably 5.0 to 70 mol%.

(Beckmann rearrangement reaction)
In the present invention, the Beckmann rearrangement reaction can be performed without solvent or in the presence of a solvent. When a solvent is used, the solvent is not particularly limited as long as it does not inhibit the reaction. For example, aromatic hydrocarbons such as benzene, toluene, xylene, cumene, and chlorobenzene; n-hexane, n-heptane , N-octane, n-nonane, cyclohexane, cyclooctane, cyclodecane, cyclododecane, and hydrocumene, and other aliphatic hydrocarbons; acetone, methyl ethyl ketone, methyl isopropyl ketone, methyl isobutyl ketone, cyclohexanone, and cyclododecanone Ketones; Nitriles such as acetonitrile, propionitrile, and benzonitrile; formamide, acetamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazoli Amides such as dimethyl sulfoxide; Sulfoxides such as dimethyl sulfoxide and sulfolane; Sulfones; Esters such as ethyl formate, methyl acetate, ethyl acetate, butyl acetate, methyl propionate, and ethyl butanoate; Formic acid, acetic acid, propionic acid, Carboxylic acids such as butanoic acid and trifluoroacetic acid; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dioxane; phosphoric acid amides such as hexamethylphosphoric triamide; chloroform, dichloromethane, dichloroethane, carbon tetrachloride, chlorobenzene And halogenated hydrocarbons such as trifluoromethylbenzene; nitro compounds such as nitrobenzene, nitromethane, and nitroethane; and hexafluoroisopropyl alcohol, trifluoroethanol, and the like Mention may be made of a fluorine-based alcohol. Of these, nitriles are preferable, and acetonitrile is more preferable. A solvent can also be used independently and may mix and use 2 or more types of solvents.

  Although the usage-amount of a solvent is not specifically limited, It is preferable that it is 0-100 weight times of an oxime compound, and it is more preferable that it is 1-50 weight times.

  The Beckmann rearrangement reaction conditions can be appropriately selected depending on the type and amount of the catalyst and solvent used, and are not particularly limited. In general, the reaction temperature is preferably 20 to 120 ° C, more preferably 50 to 110 ° C, and particularly preferably 60 to 100 ° C. The reaction pressure can be carried out under normal pressure or pressurized conditions. The reaction may be performed in an inert gas atmosphere such as nitrogen or argon, or may be performed in an air or oxygen atmosphere. In general, the reaction time is preferably 0.01 hours or longer. However, if the reaction time is too long, the production efficiency is lowered, and therefore it is more preferably 0.5 to 30 hours. As the reaction apparatus, a reactor equipped with a normal stirring apparatus can be used.

In the method for producing an amide compound according to the present invention, in the formula (1), when R ¹ and R ² are each an organic group oxime compound, Beckmann rearrangement does not include an amide bond portion in a cyclic form. An amide compound is obtained. For example, acetanilide is obtained from acetophenone oxime. When an oxime compound, which is a divalent organic group in which R ¹ and R ² are bonded to each other to form a ring, undergoes Beckmann rearrangement, a lactam is obtained. For example, cycloalkanone oxime provides a lactam having one more member ring. Specifically, ε-caprolactam is from cyclohexanone oxime, 7-heptane lactam is from cycloheptanone oxime, 8-octane lactam is from cyclooctanone oxime, and laurolactam is from cyclododecanone oxime. Is obtained.

  After completion of the Beckmann rearrangement reaction, the obtained amide compound may be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, adsorption, or column chromatography, or a combination thereof. Good.

  For example, as separation and purification after the Beckmann rearrangement reaction, the obtained amide compound-containing liquid is washed with water (a method of removing water as an aqueous solution) and / or basic washing (basic aqueous solution, an acidic catalyst component. The amide compound can be obtained by removing the catalyst component and the like. Furthermore, it may be separated and purified by distillation, crystallization or the like.

  In the present invention, after the Beckmann rearrangement reaction, it is also possible to isolate the amide compound only by filtration without performing the washing treatment as described above. It is preferable to isolate the amide compound only by filtration because inorganic salts are not by-produced.

  EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited to these Examples.

(Examples 1-8)
A Beckmann rearrangement reaction represented by the following formula (2) was performed. Specifically, in a threaded test tube, cyclohexanone oxime (56.6 mg, 0.5 mmol), catalysts (A) to (C) (catalyst (C) is PSQ-100B manufactured by Fuji Silysia Chemical Ltd.), and Acetonitrile (1 ml) was added, nitrogen was sealed, and the mixture was heated to 80 ° C. and stirred for 24 hours. The reaction mixture was diluted with ethyl acetate (10 ml), 0.4N aqueous sodium hydroxide solution (2 ml) saturated with sodium chloride was added, and the solvent was removed under reduced pressure. Dichloromethane (50 ml) was added to the residue and stirred well. Insoluble matter was filtered off and washed with dichloromethane (50 ml). The filtrate and washings were combined and concentrated under reduced pressure, and the composition ratio of the product was determined from the ¹ H NMR spectrum of the resulting reaction mixture. In each Example, the type and amount of the catalyst used, and the results are shown in Table 1. It should be noted that the total yield does not reach 100 because the product has moved to the aqueous layer and cannot be recovered (base treatment), or partly adsorbed on silica gel and cannot be recovered (simple filtration). This is thought to be the reason. ^{In the} analysis by ¹ H NMR, nothing other than cyclohexanone oxime and ε-caprolactam was found in the recovered product.

(Comparative Example 1)
The reaction was carried out in the same manner as in Example 1 except that the catalyst (A) was not used, and the composition ratio of the product was determined. The results are shown in Table 1 below.

(Comparative Example 2)
The reaction was carried out in the same manner as in Example 2 except that the catalyst (A) was not used, and the composition ratio of the product was determined. The results are shown in Table 1 below.

(Comparative Example 3)
The reaction was carried out in the same manner as in Example 1 except that the catalysts (B) and (C) were not used, and the composition ratio of the product was determined. The results are shown in Table 1 below.

  From Table 1 above, it can be seen that ε-caprolactam cannot be produced unless the catalyst (A) is used, whereas ε-caprolactam can be obtained in good yield when the catalysts (A) to (C) are used. Moreover, when Example 2 and Example 6, Example 4 and Example 7, Example 5 and Example 8 are compared, respectively, not only the increase in the catalyst (C) but also the increase in the catalyst (B), ε− It can be seen that the yield of caprolactam is improved.

(Examples 9 to 10)
The reaction was carried out in the same manner as in Example 1 except that the type of catalyst (B) was changed as shown in Table 2 below, and the composition ratio of the product was determined. The results are shown in Table 2 below.

(Comparative Example 4)
The reaction was carried out in the same manner as in Example 9 except that the catalyst (A) was not used, and the composition ratio of the product was determined. The results are shown in Table 2 below.

(Comparative Example 5)
The reaction was carried out in the same manner as in Example 10 except that the catalyst (A) was not used, and the composition ratio of the product was determined. The results are shown in Table 2 below.

  From Table 2 above, the yield of ε-caprolactam is less than 12% when the catalyst (A) is not used, whereas the yield of ε-caprolactam is as high as 80% or more when the catalysts (A) to (C) are used. -It can be seen that caprolactam is obtained.

(Examples 11-14)
The reaction was performed in the same manner as in Example 1 except that the type of catalyst (B) and the reaction temperature were changed as shown in Table 3 below, and the composition ratio of the product was determined. The results are shown in Table 3 below.

  From Table 3 above, it can be seen that ε-caprolactam can be obtained in good yield when the catalysts (A) to (C) are used even if the reaction temperature is changed.

(Examples 15 to 18)
Cyclohexanone oxime (56.6 mg, 0.5 mmol), catalysts (A) to (C), and acetonitrile (1 ml) were added to a threaded test tube, nitrogen was sealed, and the mixture was heated to 80 ° C. and stirred for 3 hours. The reaction mixture was diluted with ethyl acetate (10 ml), 0.4N aqueous sodium hydroxide solution (2 ml) saturated with sodium chloride was added, and the solvent was removed under reduced pressure. Dichloromethane (50 ml) was added to the residue and stirred well. Insoluble matter was filtered off and washed with dichloromethane (50 ml). The filtrate and washings were combined and concentrated under reduced pressure, and the composition ratio of the product was determined from the ¹ H NMR spectrum of the resulting reaction mixture. Table 4 shows the types and amounts of the catalysts used and the results in each example.

  From Table 4 above, it can be seen that, even when a sodium salt is used as the catalyst (B), ε-caprolactam can be obtained in good yield when the catalysts (A) to (C) are used.

(Examples 19 to 21)
The reaction was carried out in the same manner as in Example 1 except that the type of the catalyst (B) was changed as shown in Table 5 below, and the composition ratio of the product was determined. The results are shown in Table 5 below.

  From Table 5 above, it can be seen that even when a nickel salt is used as the catalyst (A), ε-caprolactam can be obtained in a good yield when the catalysts (A) to (C) are used.

(Examples 22 to 23)
Cyclohexanone oxime (56.6 mg, 0.5 mmol), catalysts (A) to (C), and acetonitrile (1 ml) were added to a threaded test tube, and nitrogen was sealed, followed by heating to 80 ° C. and stirring for 24 hours. The reaction mixture was diluted with ethyl acetate (10 ml), insolubles were filtered off and concentrated under reduced pressure, and the composition ratio of the product was determined from the ¹ H NMR spectrum of the resulting reaction mixture. Table 6 shows the type and amount of the catalyst used and the results in each example.

  From Table 6 above, it can be seen that, when the catalysts (A) to (C) are used, ε-caprolactam can be obtained in a good yield even by simple filtration without base washing (base treatment) after the reaction.

Claims (2)

In a method for producing an amide compound by subjecting an oxime compound to a Beckmann rearrangement reaction,
(A) Any one or more of cobalt salt and nickel salt, (B) Any one or more of magnesium salt and sodium salt, and (C) Beckmann rearrangement reaction in the presence of a catalyst composed of silica gel. Including
(A) component of the catalyst is any one or more of cobalt tetrafluoroborate hexahydrate and nickel tetrafluoroborate hexahydrate,
The component (B) of the catalyst is any one or more of magnesium sulfate, magnesium chloride, magnesium nitrate hexahydrate, sodium hydrogen sulfate, sodium sulfate, sodium hydrogen carbonate and sodium carbonate.
Method for producing an amide compound characterized by. The method for producing an amide compound according to claim 1 , wherein the amide compound is recovered after the Beckmann rearrangement reaction without performing a base treatment.