WO2004011428A1

WO2004011428A1 - Process for production of amides

Info

Publication number: WO2004011428A1
Application number: PCT/JP2003/009749
Authority: WO
Inventors: Naoko Fujita; Yuji Kawaragi
Original assignee: Mitsubishi Chemical Corporation
Priority date: 2002-07-31
Filing date: 2003-07-31
Publication date: 2004-02-05
Also published as: AU2003254791A1

Abstract

A process for producing an amide in a high yield by subjecting an oxime to Beckmann rearrangement in a liquid phase under mild reaction conditions, namely, a process for the production of amides by subjecting an oxime having eight or more carbon atoms to Beckmann rearrangement in an organic solvent in the presence of a catalyst component containing an acid anhydride, characterized in that the rearrangement is conducted at a ratio of the total molar amount of water contained in both the oxime and the solvent to the molar amount of the acid anhydride added of 15 or below.

Description

Description Method for producing amide compounds <Technical field>

The present invention relates to a method for producing an amide compound. More specifically, the present invention relates to a method for efficiently producing an amide compound by performing a Beckmann rearrangement reaction of oxime in a liquid phase in the presence of a catalyst.

In general, as a method for producing an amide compound which is industrially performed, a method of converting an oxime compound into an amide compound by a Beckmann rearrangement reaction is known. For example, ε-force prolatatam is cyclohexanone oxime. Ω-laurin lactam is produced by the Beckmann rearrangement of dodecanonone oxime by the Beckmann rearrangement reaction. At present, such a Beckmann rearrangement reaction is industrially adopted as a liquid phase reaction using a strong acid such as concentrated sulfuric acid or fuming sulfuric acid as a catalyst. However, in the method using concentrated sulfuric acid, the generated ratatam compound strongly binds to sulfuric acid. Therefore, in order to separate the ratatam compound, it is usually necessary to neutralize the sulfuric acid with ammonia. The problem is that twice the amount of ammonium sulfate (ammonium sulfate) is produced as a by-product, and the use of a large amount of strong acid leads to problems such as corrosion of the reactor. The development of catalysts for industrial use has been expected.

Therefore, various studies have been conducted on the Beckmann rearrangement reaction in the liquid phase without using a sulfuric acid catalyst. For example, in the Beckmann rearrangement reaction of cyclohexanone oxime in the liquid phase using a homogeneous catalyst, an ion pair (bismeier complex) obtained by the reaction of Ν, Ν-dimethinolephonoremamide and chlororesnolefonic acid is used as a catalyst. (MAKira and YM. Shaker, Egypt. J. Chem., 16,551 (1973)), alkylating agents formed from epoxy compounds and strong acids (boron trifluoride, etherate, etc.) and N, N-dialkyl 9 A method using a catalyst consisting of formamide (Y. Izumi, Chemistiy Letters, pp. 2171 (1990)), using cyclohexanone oxime in a heptane solvent with phosphoric acid or a condensable phosphoric acid compound. (Japanese Patent Application Laid-Open No. 62-149665) and a method using a catalyst comprising a compound such as phosphorus pentoxide and N, N-dialkylformamide (Japanese Patent No. 2652228). ), And a method using a catalyst comprising a compound such as N, N-dialkylformamide or the like containing phosphorus pentoxide or a fluorine-containing strong acid or its derivative (Japanese Patent Application Laid-Open No. 5-105564). Have been.

However, a method for producing a lactam by carrying out a Beckmann rearrangement reaction of an oxime compound in a liquid phase using these catalyst systems has not always been satisfactory as an industrial production method.

Beckmann rearrangement of a cyclic oxime compound having 8 to 15 carbon atoms in an organic solvent can be carried out using an organic sulfonic acid, an anhydride of sulfuric acid half ester, or a mixed anhydride of organic sulfonic acid and sulfuric acid half ester as a catalyst. A method of performing Beckmann rearrangement (Japanese Patent Application Laid-Open No. Hei 62-108681) is known. ■

The present inventors have repeated Example 1 described in Japanese Patent Application Laid-Open No. 62-10886'1. Force S (Because there was no commercial product of benzolsulfonic anhydride, instead!) Sulfonic anhydride was used, and the reaction scale was 1 Z4), and the catalyst was not dissolved in the solvent but was dispersed in the reactor as a solid, and as described in the Examples, A strong heat is generated immediately. "The phenomenon was not observed. Further, the ratatam yield after 0.5 hour was examined by NMR, but the ratatam yield was only 0.5%, and the Example could not be reproduced (Comparative Example 1 of the present application).

Thus, the catalytic Beckmann rearrangement was not satisfactory with an industrial production method.

On the other hand, the present inventors have proposed a method of Beckmann rearrangement of an oxime compound as a catalyst system containing a non-fluorine-containing sulfonic anhydride having high catalytic activity and N, N-disubstituted amide, or sulfonic acid or sulfonic acid. Compounds selected from anhydrides and N, N— A catalyst system containing a disubstituted amide and a carboxylic acid anhydride was proposed (WO O 1/813002).

In the past, even in such catalytic Beckmann rearrangement reactions, the separation of a catalyst component having a strong acid property from an amide compound having a basic property and an unreacted oxime compound requires a catalyst component. It has been considered that it is essential to remove the catalyst by a neutralization step or by adding water to the reaction solution and by washing or washing. However, when the amide compound and the unreacted oxime compound are separated from the catalyst component after the neutralization step, the acid component is converted into a salt by neutralization, and thus the catalyst component is discarded as it is, or When it was necessary to recover and reuse the catalyst components, the salts had to be converted to acids before the catalyst had to be dehydrated. In addition to these problems, the catalyst component must be neutralized while containing a large amount of the amide compound, which makes the reactor for neutralization extremely large, dissolving the amide compound. Therefore, a large amount of solvent is required. When the amide compound present in a large amount inhibits the neutralization reaction of the catalyst, there has been a problem. ——:.

In addition, when water is added and Z or washing is performed, if the active catalyst is weak, the catalyst is completely deactivated, so the separated catalyst component is returned to the rearrangement step as it is to recycle the catalyst solution. I couldn't. Even when the catalyst is deactivated, if the catalyst components are dehydrated and regenerated to acid anhydrides, a large amount of water used must be removed from the aqueous phase containing the catalyst components It was economically disadvantaged.

Furthermore, a method for industrially converting an acid derived from an acid anhydride as a catalyst component into an anhydride has not been established, and the catalyst component could not be substantially regenerated and recycled to the Beckmann rearrangement reaction step. .

The inventors of the present invention have conducted intensive studies. As a result, when oxime is produced by a general method, the oxime compound contains about 5 to 15% by weight of water, and water is usually present in the organic solvent. Therefore, a certain amount of water is inevitably present in the reaction system, but it has been found that the amide compound can be produced with high efficiency by reducing the amount of water. Furthermore, the amide compound and the unreacted oxime compound are reacted with the catalyst from the reaction solution. The present inventors have found a method for directly separating the components and obtaining an amide compound, and at the same time, have found a method for regenerating the catalyst component.

That is, a first gist of the present invention is a method for producing an amide compound by subjecting an oxime compound having 8 or more carbon atoms to a Beckmann rearrangement reaction in an organic solvent in the presence of a catalyst component containing an acid anhydride. The present invention also provides a method for producing an amide compound, wherein the rearrangement reaction is carried out by setting the total molar ratio of the oxime compound and water contained in the solvent to 15 or less with respect to the added acid anhydride.

Further, a second gist of the present invention is a method for producing an amide compound by subjecting an oxime compound to a Beckmann rearrangement reaction in an organic solvent in the presence of a catalyst component containing an acid anhydride. The present invention is directed to a method for producing an amide compound, which comprises directly separating a catalyst component and an amide compound from the amide compound.

Hereinafter, details of the present invention will be described. '

As the starting oxime compound used in the Beckmann rearrangement reaction of the present invention, an oxime compound having 8 or more carbon atoms is used in the first invention, and usually has 20 carbon atoms or less, preferably 1 carbon atom. Use up to three oxime compounds. As the oxime, an oxime of an alicyclic ketone or an oxime of a substituted alicyclic ketone is preferable. Above all, cyclodecanonone oxime, cyclodexamedecoxime, cyclodexodenonoxime, more preferably cycloundecanone oxime, cyclodexcanone oxime are used.

The oxime compound used in the second invention of the present invention is not limited, and a known oxime compound is applied. Specific examples of the oxime compounds include cyclohexanone oxime, cyclopentanone oxime, cyclododecanonoxime, acetone oxime, 2-butanone oxime, acetophenone oxime, benzophenone oxime, and 4'-didroxyacetophenone. Oxime compounds having 2 to 20 carbon atoms, preferably 3 to 13 carbon atoms, such as oxime. Inside Also used are cyclic oximes having 4 to 20 carbon atoms, preferably 8 or more carbon atoms, such as cyclohexanone oxime, pentanone oxime, cycloundecanone oxime and cyclododecanone oxime, and particularly cycloundecanonone oxime. Cyclodode canonoxime is suitable because it is easily separated by crystallization.

In addition, as these oxime compounds, salts such as oxime hydrochloride can be used. In this case, as the oxime hydrochloride, a cycloalkane obtained by photosodium oxidation in the presence of hydrogen chloride can be used, and a product obtained by bringing oxime into contact with hydrogen chloride can also be used.

Conventionally, to achieve complete rearrangement using oxime hydrochloride as a substrate, the molar ratio of hydrochloric acid / oxime in the reaction system must be 2 or more, the amount of hydrochloric acid used is large, and the material and operability of the reactor 31. (1 981) 250 .; Japanese Patent Publication No. 47-181114; Japanese Patent Publication No. 52-17035; DE 1, 620, 478).

In the present invention, when this oxime hydrochloride is used, the reaction can proceed sufficiently even if the molar ratio of hydrochloric acid / oxime in the reaction system is less than 2. The molar ratio of Z oxime hydrochloride is more preferably 1.3 or less, and further preferably less than 1.1. Here, the amount of hydrochloric acid in the reaction system includes not only hydrogen chloride constituting oxime hydrochloride but also hydrogen chloride contained in the reaction solution in the number of moles of hydrogen chloride. Further, when oxime hydrochloride is used as a raw material for oxime, the Beckmann rearrangement reaction can be advanced without using a catalyst component containing an acid anhydride.

Catalyst component>

The catalyst component used in the Beckmann rearrangement reaction of the present invention is not particularly limited as long as it is a catalyst component containing an acid anhydride, but it is preferable to use an acid anhydride which generates a strong acid when hydrolyzed. . The strong acid is not particularly limited, but a strong acid having a pKa of 4 or less is more preferable.

Specific examples of the catalyst component containing an acid anhydride include (1) an acid anhydride that produces a strong acid upon hydrolysis, (2) carboxylic acid anhydride, and a strong acid and a diacid or a strong acid anhydride. It is.

(1) Acid anhydrides that produce strong acids by hydrolysis

The acid anhydride that produces a strong acid upon hydrolysis may be any of a strong acid and a strong acid anhydride, and a strong acid and a weak acid anhydride. Specifically, sulfonic anhydrides such as aromatic sulfonic anhydride and aliphatic sulfonic anhydride, fluorinated anhydride such as trifluoromethanesulfonic anhydride, and pentoxide, which is an anhydride of phosphoric acid. Phosphorus, rhenium pentoxide which is an anhydride of perrhenic acid, sulfur trioxide which is an anhydride of sulfuric acid, boron phosphate which is an anhydride of phosphoric acid and boric acid, and anhydride of a half ester of sulfuric acid are more preferred. May be mixed acid anhydride. Here, the anhydride of sulfuric acid half esters of the general formula _{R- OS 0 2 _ 0- OS 0} 2 - R, ( where R and R, are also good C 1-2 0 be different, better good at the same Or an aliphatic group having 1 to 10 or an aromatic group having 6 to 20 carbon atoms, preferably 6 to 10 carbon atoms, and may contain a halogen, but is usually an alkyl group. And R ′ may be ring-closed).

Of these, sulfonic anhydride and phosphorus pentoxide are preferred, and sulfonic anhydride is preferred in terms of easier handling. The sulfonic anhydride is not particularly limited, and aromatic sulfonic anhydride, linear or cyclic aliphatic sulfonic anhydride and the like can be used. The aromatic sulfonic anhydride usually has 6 to 20 carbon atoms, preferably 6 to 10 carbon atoms, and may have a substituent on the aromatic ring. The aliphatic sulfonic anhydride usually has 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, and may have a substituent. Here, the substituent represents an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, an acyl group having 2 to 4 carbon atoms, or a halogen atom such as F, Cl, or Br.

Specific compounds include benzenesulfonic anhydride, ρ_toluenesulfonic anhydride, m-xylene-14-sulfonic anhydride, p-dodecylbenzenesulfonic anhydride, 2,4-dimethylbenzenesulfonic anhydride, 2,5-Dimethylbenzensnolefonic anhydride, 4-monobenzenebenzenesnolefonic anhydride, a-naphthylsnolefonic anhydride,] 3-Naphthylsulfonic anhydride, biphenylsulfonic anhydride, methanesulfonic anhydride Product, ethanesulfonic anhydride, pulppansulfonic anhydride, 1-hexanesulfonic anhydride, 1-octanesulfonic anhydride, trifluoromethanesulfonic acid, a mixed acid anhydride of p-toluenesulfonic acid and methanesulfonic acid, etc., and among them, p-toluenesulfonic anhydride And methanesulfonic anhydride are preferred.

The amount of acid anhydride results in a strong acid by hydrolysis, is not particularly limited, in general, about relative Okishimu the starting compounds of 0.1 to 2 0 mole ^_0/0, preferably 0. 3 It is used in an amount of 15 mol%, more preferably 0.5 to 10 mol%. If the amount is less than this range, sufficient catalytic activity cannot be obtained. On the other hand, if the amount is too large, the load required for the catalyst treatment after the rearrangement reaction increases, which is not preferable. ·

(2) Carboxylic anhydrides and strong acids and Z or strong acid anhydrides.

Further, when a carboxylic acid anhydride and a strong acid and / or a strong acid anhydride are used as the acid anhydride, the carboxylic acid anhydride is not particularly limited. It is possible to use an aliphatic carboxylic anhydride having a good carbon number of 1 to 20, preferably 1 to 8 and an aromatic carboxylic anhydride having 6 to 12 carbon atoms which may have a substituent. Yes (where the substituent represents an alkyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, an acyl group having 2 to 4 carbon atoms, a halogen atom such as Cl, Br, and F) ). The valence of the carboxylic acid is not particularly limited, and is preferably a force S, preferably monovalent. Specific compounds include acetic anhydride, propionic anhydride, n-butyric anhydride, n-valeric anhydride, n-caproic anhydride, n-heptanoic anhydride, 2-ethylhexanoic anhydride Examples thereof include benzoic anhydride, phthalic anhydride, maleic anhydride, and succinic anhydride. Among them, acetic anhydride and propionic anhydride, which are low-boiling compounds, are preferred in the present invention.

Although the amount of the carboxylic acid anhydride used in the present invention is not particularly limited, it is generally based on at least one compound selected from the group consisting of strong acids and / or strong acid anhydrides described below. It is used in a range of about 0.5 to 200 mole times, preferably 1.0 to 100 mole times, and more preferably 2.0 to 50 mole times. If the amount is less than this range, sufficient catalytic activity cannot be obtained. On the other hand, if the amount is too large, the load required for catalyst separation after the rearrangement reaction increases, which is not preferable. The “strong acid anhydride” in the strong acid and Z or the strong acid anhydride may be a strong acid and a weak acid anhydride or a strong acid and a strong acid anhydride. As the strong acid and the strong acid anhydride, a compound selected from sulfonic acid and / or an acid anhydride thereof is preferable. The compound selected from sulfonic acid and / or an acid anhydride thereof is not particularly limited, and may be an aromatic sulfone having 6 to 20 carbon atoms, preferably 6 to 10 carbon atoms which may have a substituent. An acid, an aliphatic sulfonic acid having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms which may have a substituent, and an acid anhydride thereof can be used (where the substituent is a carbon atom). An alkyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, an acyl group having 2 to 4 carbon atoms, and a halogen atom such as F, Cl, or Br).

Specific compounds include benzenesulfonic acid,: —toluenesulfonic acid,; _toluenesulfonic acid monohydrate, monododecylbenzenesulfonic acid, 2,4-dimethylbenzenesulfonic acid, 2,5-dimethylbenzenesulfonic acid Acid, 4-chlorobenzene zensnolephonic acid, 4-funoleo-benzene benzenesnolephonic acid, α-naphthinolesnolephonic acid,] 3-naphthinolesnolephonic acid, bifu. Soil nilsnolefonic acid, methanesnolefonic acid, trifluoromethanesnole Examples thereof include sulfonic acid, ethanesulfonic acid, sulfonic acid, sulfonic acid, 1-hexanesulphonic acid, 1-octanesulfonic acid, and acid anhydrides or mixed acid anhydrides thereof, among which methanesulfonic acid, trifluoromethanesulfonic acid, Ethane Snorefonic acid, Proha. Preferred are snolefonic acid, benzenesnolefonic acid,: — tonoleensnorefonic acid,: ρ-dodecylbenzenesulfonic acid and their acid anhydrides or mixed acid anhydrides, particularly methanesulfonic acid, ρ-toluenesulfonic acid and Acid anhydrides are preferred.

The amount of a compound selected from strong acids and Ζ or strong anhydride in the present invention is not particularly limited, but is generally about relative Okishimu the starting compounds of 0.1 to 2 0 mole ^_0/0 , preferably from 0.3 to 1 5 moles ^_0/0, used more preferably in the range of 0.5 to 1 0 mol%. If the amount is less than this range, sufficient catalytic activity cannot be obtained. On the other hand, if the amount is too large, the load required for the catalyst treatment after the rearrangement reaction increases, which is not preferable.

Solvent> The solvent that can be used in the rearrangement reaction of the present invention is not particularly limited as long as it does not inhibit the rearrangement reaction, but usually an organic solvent having 1 to 20 carbon atoms is used. For example, aliphatic hydrocarbon compounds such as n-hexane, n-heptane, n-dodecane, and cyclohexane; aromatic hydrocarbon compounds such as benzene, toluene, xylene, mesitylene, monochrome benzene, and methoxybenzene; Acetonitrile, propanitrile, forcepronitrile, aprotolyl, benzoetrile, tonorenitrile, etc.-tolyl compounds, dimethyl phthalate, dibutyl phthalate, dimethyl malonate, dimethyl succinate, etc., N, N N, N-disubstituted amide compounds such as dimethylformamide, N, N, NN 'Other amides such as tetramethylurea, ethers such as tetrahydrofuran, dioxane, diethylene glycol dimethyl ether, dimethyl Examples of sulfoxides such as sulfoxide and sulfolane These can be used alone or in combination. Preferably, a solvent selected from an aromatic hydrocarbon compound, an aliphatic hydrocarbon compound and a -tolyl compound is used. These compounds may have a substituent such as an alkyl group, an acyl group, a nitro group, a hydroxyl group and a halogen atom.

Among these solvents, a solvent that dissolves the catalyst under the reaction conditions is more preferable because the reaction rate may decrease if the catalyst is not dissolved.

In addition, when oxime hydrochloride is used as a raw material, the Beckmann rearrangement reaction can proceed without using an acid anhydride catalyst. It is preferable to use a nitrile compound, a nitro hydrocarbon, or a halogenated hydrocarbon, and it is more preferable to use a nitrile compound.

The amount of the solvent to be used is not particularly limited, but it is usually 1 to 100 times, preferably 2 to 10 times the weight of the oxime compound.

In the first invention of the present invention, the reaction is carried out by controlling the total molar ratio of the oxime compound and water contained in the reaction solvent to 15 or less with respect to the added acid anhydride. The molar ratio is preferably 10 or less, more preferably 6 or less, and particularly preferably 3 or less. By limiting the molar ratio, the yield of the target amide compound or the amount (TON) of the amide compound formed per unit catalyst can be improved.

When oxime hydrochloride is subjected to Beckmann rearrangement in a nitrile solvent without an acid anhydride, the molar ratio is preferably 0.5 or less, more preferably 0.1 or less, and further preferably 0.05 or less. Is preferred.

The measurement of the water content in the present invention may be performed by a known method, for example, a Karl Fischer method can be used.

In order to determine the molar ratio of the total amount of water contained in the oxime compound and the reaction solvent to the acid anhydride, it is determined by the amount of the compound charged in the reactor in the case of a batch reaction, and in the case of a continuous reaction, It may be determined based on the amount of the compound introduced into the reactor per unit time. Also, when the catalyst component is separated from the reaction solution as described below and the catalyst component is recycled to the reactor without going through the catalyst regeneration process, the amount of “acid anhydride” in the preparation is not counted here. . “Charged anhydride” refers to an acid anhydride newly introduced into the reaction system and a regenerated acid anhydride.

In this reaction, an acid anhydride is used, but it is known from R that the acid anhydride gradually changes to a corresponding acid or a derivative containing an acid component during the reaction. Therefore, in the present invention, the ratio of water present in the reaction system to the total of the derivative containing the acid and the acid component corresponding to the acid anhydride in the reaction system is usually less than 7, and Among them, 5 or less is preferable, 3 or less is preferable, and 1.5 or less is particularly preferable.

When measuring the amount of water present in the reaction system, if the Karl Fischer method is used, for the reasons described below, if the undissolved acid anhydride is present, the acid anhydride is used. It is preferable to measure and sum the solid and the solution, respectively, when the oxime compound as the raw material or the amide compound as the target product is present as the solid content. Since acid anhydrides are gradually hydrolyzed by water, if a sample mixed with acid anhydrides is introduced into a moisture measuring device, it may affect the amount of water during analysis. In addition, the oxime compound as the raw material and the amino acid as the target product are used as solids. If a compound exists, it may contain water, so it is necessary to measure the water content. However, if the water content is measured by partially sampling the solid content and the solution in a slurry state, the error from the original solution composition tends to increase. For this reason, when acid anhydride or solid content and a solution are measured together, an accurate amount of water may not be obtained.

Further, as a general industrial production method of an oxime compound, a method of reacting a ketone with hydroxylamine sulfate, a method of producing a cyclium alkane by photo-to-sophorization, and the like are known. The oxime compound obtained through such a production method generally contains about 5 to 15% by weight of water. In addition, although the reaction solvent also depends on the type, the reaction solvent usually contains water of the number 100 ppm, and in some cases, the water of the number 100 ppm. It may contain more water depending on the storage method. In addition, the reactor and its associated receiver and piping also have moisture on the walls. In the present invention, the total molar ratio of the water contained in the oxime compound and the reaction solvent is reduced to a specific value or less with respect to the acid anhydride used. In addition, since it is preferable to limit the water content in the reaction liquid phase, it is preferable to dry not only these but also the reactor and the associated receiver. '

The acid anhydride to be used is preferably stored in a manner not to be mixed with water, and the rearrangement reactor, the receiver and the piping are preferably dried. In order to avoid the incorporation of moisture into the reaction system, the preparation and the reaction of the reaction are preferably carried out in an atmosphere of a dried gas, and it is preferred to avoid the incorporation of moisture-containing air. Usually performed in an inert gas atmosphere such as nitrogen, argon or helium, but dry air can also be used. In order to remove water in the reaction solution, a water absorbing agent may be present in the reaction solution, or the reaction may be performed while removing water.

How to limit the amount of water flowing>

The above-described oxime compound, reaction solvent and reaction atmosphere gas, and a method for drying the reactor are not particularly limited, but are preferably performed in the following steps, respectively.

(1) Oxime compound

The starting oxime compound of the method of the present invention is usually at most 5% by weight, preferably at most 1. 5 weight. / ₀ or less, more preferably 0.6% by weight or less, particularly preferably 0.3% by weight or less.

Specific examples of the method for drying the oxime compound include general distillation, distillation using a thin film evaporator, crystallization, and drying under reduced pressure of solid oxime. These methods may be appropriately combined.

(2) Organic solvent

The organic solvent of the present invention generally has a water content reduced to 1% or less, preferably 0.2% or less, more preferably 0.1% or less, and particularly preferably 0.05% or less. Is preferred.

Examples of the method for drying the organic solvent include general distillation, distillation using a thin film evaporator, drying using molecular sieves, a method using metallic sodium, etc., salts such as sodium sulfate and magnesium sulfate. For example, a method such as drying using a method can be used. These can also be combined. If the organic solvent is sufficiently dried, this step need not necessarily be included.

(3) Reaction atmosphere gas.

Examples of a method for drying the gas in the reaction atmosphere include a method of incorporating a moisture absorbent such as molecular sieves between gas pipes leading to the reactor. May not necessarily be included.

(4) Rearrangement reactor and receivers and piping associated with the reactor

In addition, as a method for drying the rearrangement reactor and the receivers and pipes attached to the reactor, the drying gas is circulated in advance, the drying gas is circulated while keeping the temperature, or the moisture is removed by a method such as drying under reduced pressure. A method or the like can be adopted.

By appropriately combining the degree of drying of the oxime compound and the reaction solvent obtained through the above-described drying step, the amount of water to be charged can be brought to a predetermined state.

In this reaction, an acid anhydride is used.When a reaction raw material or solvent is mixed with a catalyst acid anhydride, the acid anhydride is hydrolyzed by water adhering to the reaction raw material or solvent or to the reactor. However, water may be consumed. Therefore, it is the raw material of the reaction and the catalyst Before and after mixing (after hydrolysis of the anhydride), the amount of water measured may vary. In this reaction, the amount of water in the reaction atmosphere and the reactor should be limited so that the molar ratio of water in the raw materials added to the reaction to the acid anhydride is not more than a predetermined amount, and the amount of water in the reaction solution itself should not be increased. Is preferred. In the present invention, the yield of the target amide compound can be improved by reducing the amount of water with respect to the acid anhydride used as described above.

Although the conditions for carrying out the method of the present invention are not particularly limited, the reaction temperature is usually from o ° C to 200 ° C, preferably from 40 ° C to 150 ° C, more preferably from 50 ° C to 150 ° C. It is carried out in the range of 30 ° C.

The reaction pressure is not particularly limited, and the reaction can be carried out under reduced pressure, normal pressure and pressurized conditions.

The reaction time or the residence time of the reaction substrate in the reactor is usually from 10 seconds to 10 hours, preferably from 1 minute to 7 hours.

In the present invention, the rearrangement reaction proceeds even if the acid anhydride and the starting oxime compound are mixed in any order. For example, the raw material oxime may be mixed with an organic solvent, and after reaching a predetermined temperature, an acid anhydride may be added, or a mixture of the acid anhydride mixed with the organic solvent, or a smaller amount of the raw material oxime added to the mixture. The mixture to which the compound has been added is heated to a predetermined temperature, and then the raw material solution in which the raw material oxime compound is dissolved may be added at once, or the reaction may be started by sequentially supplying the raw material oxime compound.

The starting oxime compound may be dissolved in a part of the solvent and used for the reaction, or may be added as it is without being dissolved.

Ku rearrangement reaction form>

The reaction mode for carrying out the reaction of the present invention is not particularly limited, and the reaction can be carried out in any of a batch reaction and a continuous flow reaction. However, industrially, it is preferable to use a continuous flow reaction mode. The type of the reactor is not particularly limited, and a general reactor such as a reactor having one or two or more continuous stirring tanks or a tubular reactor can be used. Further, the anhydride used in the present invention is a reaction It is preferable to use a corrosion-resistant material for the reactor because it is hydrolyzed by water contained in the liquid to generate an acid. For example, stainless steel, Hastelloy, Monel, Inconel, titanium, titanium alloy, dinoleconium, zirconium Examples include alloys, nickel, nickel alloy, tantalum, or fluororesins, and materials coated with various types of glass on the inside.

Although the reaction method of the present invention is not particularly limited, for example, it may be batch or continuous, and it is preferable to carry out the reaction continuously from the industrial point of view.

In the case of a continuous flow reaction, a catalyst component containing the acid anhydride of the present invention, specifically, a strong acid anhydride or a carboxylic acid anhydride and a strong acid and / or a strong acid anhydride are placed in a sufficiently dried reactor. The catalyst solution in which the substances are dissolved is charged and maintained at a predetermined temperature. 'The reaction is carried out continuously with the solvent in which the raw material oxime compound is dissolved and reacted during the desired residence time, and simultaneously the amide compound, unreacted oxime compound and catalyst component, and the reaction containing the solvent The mixture is continuously removed.

Reaction mixture>

The reaction mixture after the rearrangement reaction is composed of a low-boiling product, a solvent, an amide compound as an intended product, unreacted oxime, and the remaining catalyst components (a carboxylic acid anhydride and a strong acid and / or a strong acid anhydride as catalyst components). (When used, carboxylic acid is included.)

Separation of catalyst components from amide compounds>

In the present invention, it is desirable to directly separate the catalyst component and the amide compound from the reaction mixture after the rearrangement reaction. By directly separating the catalyst, the amide compound can be easily separated from the catalyst component, and the catalyst can be easily regenerated.

Here, separating the catalyst component and the amide compound means separating the reaction solution without neutralization, addition of water and z or washing. In the present invention, the term "neutralization" refers to the addition of a base in an amount equal to or more than that of the existing acid, and the term "water addition and / or washing" refers to the addition of 30% by weight or more of water to the reaction mixture. Say.

The step of separating the amide compound, the unreacted oxime compound and the catalyst component may be carried out from the reaction solution after the catalyst has been deactivated or from the reaction solution if the catalyst has not been deactivated. The mother liquor containing the catalyst component after separation of the amide compound and unreacted oxime compound may be led to the catalyst regeneration step or may be recycled to the rearrangement step without being led to the regeneration step. You can choose.

In the case of leading to the regeneration step, it can be led in the form of an acid, or if necessary, can be regenerated to an acid after the neutralization step and further to an acid anhydride. Since the amide compound and the separated catalyst component are led to the neutralization step after separating a large amount of the amide compound, the neutralization can be easily performed.

On the other hand, the separated amide and oxime compounds are separated into amide and oxime compounds by various separation operations such as distillation, extraction, and crystallization separation. The target amide compound can be further purified by a method such as distillation or crystallization to obtain a higher purity product.

The unreacted oxime compound separated from the target amide compound can be appropriately purified and used as a reaction raw material. It is not necessary to separate the unreacted oxime compound from the amide compound, provided that Beckmann rearrangement reaction conditions in which the unreacted oxime compound does not remain are selected.

'<Separation method>.'

As a method for separating the catalyst component from the solvent, the amide compound, the unreacted oxime compound and the catalyst component from the rearrangement reaction solution, any known method such as distillation, crystallization, or extraction can be employed. Crystallization is preferred because it is simple and the equipment is simple.

In the case of crystallization, the solvent used in the reaction can be used as it is, or part or all of the solvent used in the reaction is distilled off, and another solvent such as toluene is added, and the crystallization is performed. May be done.

According to this method, the crystallization of the rearrangement reaction solution precipitates an amide compound containing almost no catalyst component as a solid component, and the catalyst component is recovered in the filtrate.

When a carboxylic acid is contained as a catalyst component, it is preferable to distill the carboxylic acid by distillation before crystallization. The removed carboxylic acid can be recycled to the reaction step after being converted to the anhydride.

The amount of the solvent used for crystallization is not particularly limited, but is usually The amount is usually 0.5 to 20 times, preferably 1 to 10 times, and more preferably 2 to 7 times the total weight of the compound and the unreacted oxime compound. In the crystallization operation, any crystallization temperature may be used. Usually, a temperature from the melting point to the boiling point of the solvent to be used is used, but a temperature between 110 ° C. and room temperature is preferable. For separation of the amide compound and the unreacted oxime compound from the catalyst component, known methods such as ordinary atmospheric pressure filtration, vacuum filtration, and pressure filtration can be used. The amide compound and the unreacted oxime compound separated by filtration can be used to wash the catalyst component attached to the crystal surface with a solvent. ,

If the catalyst solution after separating the catalyst component, the amide compound and the unreacted oxime compound from the reaction solution is returned to the rearrangement step as it is, the catalyst is deactivated by moisture, so these separation operations must be performed in a dry atmosphere. It is preferable not to mix water by a method such as performing, or collecting a solution in which the catalyst component is dissolved using a dried syringe or the like. In addition, even when regeneration of the catalyst is necessary, it is preferable to prevent water from being mixed into the catalyst solution by the method described above. '

When water is used as a poor solvent to increase the crystallization efficiency, the amount of water is 30% by weight or less based on the rearrangement reaction solution, and 20% by weight considering the burden of water separation operation. . / ₀ or less, preferably 15% by weight or less. '' The mode of operation in this step is not particularly limited, and the catalyst component and the amide compound can be separated as they are in the reactor used for the reaction, or they can be transferred to another container and then performed. Good. In addition, it can be implemented in either a batch format or a continuous distribution format.

In this step, since an acid anhydride or an acid derived from the acid anhydride is present in the reaction system, it is preferable to use a corrosion-resistant material for the reactor, such as stainless steel, Hastelloy, Monel, Inconel, or the like. Examples thereof include titanium, a titanium alloy, a zinc alloy, a zinc alloy, nickel, a nickel alloy, tantalum, a fluororesin, and a material in which various kinds of glass are coated on the inside.

The catalyst component separated after the Beckmann rearrangement reaction is dissolved in a solvent It can be recycled to the reaction system as it is, but it can be recycled to the rearrangement reaction system after conversion to the acid anhydride. At that time, if necessary, a neutralization step and a regeneration to an acid may be performed, and then a step of acid anhydride may be conducted.

The method of regenerating the catalyst component will be explained in the following three steps.

(1) A step of neutralizing an acid derived from an acid anhydride with an alkaline compound to form an acid salt of the acid

(2) A step of regenerating an acid derived from an anhydride from an alkali salt of an acid derived from an acid anhydride

(3) Step of dehydrating and condensing the regenerated acid to regenerate the acid anhydride If the neutralization step is unnecessary, steps (1) and (2) are omitted. Hereinafter, each of the steps will be sequentially described.

(1) A step of neutralizing an acid derived from an acid anhydride with an alkaline compound to form an alkali salt of the acid.

When the catalyst component separated after the Beckmann rearrangement reaction is regenerated through a neutralization step, the following method is preferable. ''

(Alkaline compound)

-Any alkaline compound may be used, but preferably an alkali metal hydroxide, an alkaline earth metal hydroxide, or ammonia is used. These alkaline compounds are preferably mixed with water in advance and used as an aqueous alkaline solution.

(Neutralization conditions)

The temperature at which the catalyst component and the alkaline compound are mixed is generally 0 to 200 ° C, preferably 10 to 150 ° C. The amount of the alkaline compound used is usually 0.1 to 20 mol times, preferably 0.5 to 10 mol times, relative to the acid anhydride used for the rearrangement reaction.

When neutralized with an aqueous solution of an alkaline compound, the solution containing the neutralized catalyst component contains a reaction solvent, a low-boiling by-product, and water in addition to the catalyst component. The neutralized solution contains the target amide compound and the starting oxime compound. In such a case, the target amide compound and unreacted oxime compound can be separated from the acid derived from the acid anhydride by a method such as extraction, crystallization, or distillation. By distilling off the reaction solvent and light-boiling by-products from the solution containing the neutralized catalyst component, the neutralized salt of the catalyst component can be obtained in the form of an aqueous solution. The recovered solvent can be recycled to the reactor. In this case, unnecessary by-products are separated and removed by a separate means such as distillation.

(2) Step of Regenerating Acid Derived from Acid Anhydride from Acid Salt Derived from Acid Anhydride The alkali salt of a neutralized acid is regenerated from the alkali salt to an acid using another acid. (Acid used for regeneration)

Examples of other acids used in this step include inorganic acids such as sulfuric acid, hydrochloric acid, and nitric acid, organic acids such as acetic acid and propionic acid, solid acids, and acid-type ion exchange resins. If the acidity of the acid derived from the acid anhydride is stronger than the acidity of the other acid used for acid regeneration, the amount of the other acid used is increased or the free acid is used. The acid can be recovered by removing the strong acid out of the system during the process, even if it is disadvantageous for the equilibrium of the reaction.

The case where the acid derived from the acid anhydride is sulfonic acid will be described below with reference to examples. Conventionally, when an alkaline salt of sulfonic acid is brought into contact with another acid, there is a restriction in equilibrium, it is very difficult to push the reaction over, and it is necessary to use a large excess of the other acid. In that case, other acids had to be discarded or separated and recovered again, which was not an economically effective method.

(Organic solvent)

In this step, the reaction is preferably performed in the presence of an organic solvent in which the sulfonic acid is soluble. As the organic solvent, it is preferable to use an organic solvent in which the sulfonic acid is dissolved and the inorganic acid is hardly dissolved. Specifically, aromatic hydrocarbons such as toluene and benzene, aliphatic hydrocarbons such as hexane and octane, ketones such as acetone and methylethyl ketone, esters such as ethyl acetate and methyl phthalate, Examples thereof include ethers such as dimethyl ether, -tolyls such as acetonitrile, and alcohols such as ethanol and isopropanol. Among them, the solubility of sulfonic acid is high, Since the solubility of the alkali salt is low, aromatic hydrocarbons and aliphatic hydrocarbons are preferably used.

In the presence of such an organic solvent, the sulfonic acid generated from the sulfonic acid salt and the inorganic acid dissolves in the organic solvent, is removed outside the system of the salt exchange reaction, and the equilibrium easily shifts to the sulfonic acid generating side, Sulfonic acid can be obtained with good yield.

For example, in the case of p-toluenesulfonic acid, the solubility in toluene is low in the form of an ammonium salt, and the solubility in toluene is improved in the form of a free acid. Therefore, it is produced by contact with other acids in the presence of toluene! ) One toluenesulfonic acid can be transferred to a toluene layer in which other acids are not dissolved, so that the equilibrium can be improved. .

The solubility of the sulfonic acid in the organic solvent is not particularly limited as long as the sulfonic acid generated in the reaction system can be dissolved, but is preferably 0.1% by weight. /. And more preferably 1% by weight or more.

The amount of the organic solvent to be used is from 0.5 to 100 parts by weight, preferably from 2 to 100 parts by weight, based on 1 part by weight of the sulfonic acid.

(Reaction conditions)

The other acid is preferably an inorganic acid, more preferably sulfuric acid. 'When an alkali salt of a sulfonic acid is used as an alkali salt of an acid and sulfuric acid is used as another acid, the amount of the sulfuric acid to be used is usually 0.1 to 10 mole times the alkali salt of the acid. Preferably, it is 0.5 to 5 mole times. The reaction temperature of the salt exchange can be usually carried out in the range of 0 to 200 ° C, preferably in the range of 20 to 180 ° C. Although the reaction time is not particularly limited, it is selected from 1 minute to 100 hours.

In addition, in the state of an acid such as p-toluenesulfonic acid, it may have water of crystallization. In such a case, since the solubility in the organic solvent is low, it is possible to dissolve the sulfonic acid in the organic solvent by removing the water of crystallization by operating using a solvent azeotropic with water and distilling off with the solvent and water. It is possible to obtain a high yield.

For example, when toluene is used as a solvent, water contained in an alkali salt of sulfonic acid or another acid used can be distilled off together with toluene. At this time Although the reaction temperature depends on the amount of coexisting water, when a small amount of water coexists, toluene and water flow out from a temperature lower than the boiling point of toluene under the operating pressure, and as the removal of water proceeds, It approaches the boiling point of Truen. This reaction proceeds sufficiently when the reaction is maintained under such temperature conditions. After phase separation between the distilled toluene and water, toluene can be used again as a solvent.

(Separate)

After the salt exchange reaction, the sulfonic acid is dissolved in the organic solvent, and the salt of the inorganic acid and the inorganic acid are present in an insoluble form in the organic solvent. By separating the organic phase from the reaction solution, the sulfonic acid can be recovered. Further, sulfonic acid can be isolated by a method such as distillation of a solvent or crystallization separation of sulfonic acid.

On the other hand, when an ion exchange resin or a solid acid is also suitably used, a regeneration treatment can be performed by packing these in a packed column or the like and flowing an aqueous solution of an acid alkali salt.

(Impurities in alkali salts)

Further, a solvent, an amide compound, or an impurity derived from the reaction may be mixed in the alkali salt of the acid derived from the acid anhydride. If such a compound is present in excess, the regeneration reaction to the acid may be inhibited, or the purity of the obtained acid may be reduced. In such a case, if necessary, the alkali salt of the acid is purified, and the number of moles of the amide compound and the unreacted oxime compound contained in 1 mole of the alkali salt is 0.2 or less, more preferably 0 or less. It is preferable to subject it to a contact treatment with another acid after reducing it to 1 or less.

Examples of purification methods include crystallization of impurities, extraction of alkali salts of acids with water, extraction and removal of impurities with organic solvents, solvent washing, distillation and removal of low-boiling impurities, and purification by crystallization. . When the acid derived from the acid anhydride is sulfonic acid, for example, the target amide compound and the starting oxime compound can be precipitated in the form of an aqueous solution of an alkali salt of sulfonic acid and removed from the aqueous solution of the alkali salt of sulfonic acid. . At this time, the amount of water in which the neutralized salt is dissolved is not particularly limited if the neutralized salt is ammonium p-tonolenesulfonic acid, as long as the salt is dissolved in water. However, if the amount is too small, it is neutralized: —Ammone-toluenesulfonic acid cannot be sufficiently extracted into the aqueous phase, and if it is too large, the target amide compound and the starting oxime compound are converted to salts. It is disadvantageous because it is mixed and the load of water removal in the next process increases. In this case, the amount of water contained is usually 1 to 10 times, preferably 2 to 5 times the weight of the neutralized salt.

The reaction format in this step is not particularly limited, and it can be carried out in either a batch reaction or a continuous flow reaction. However, the continuous flow reaction format is industrially preferable. The type of the reactor is not particularly limited, and a general reactor such as a reactor having one or more continuous stirring tanks or a tubular reactor can be used.

In this step, an acid anhydride, an acid derived from an acid anhydride, or another acid that regenerates an alkali salt of an acid derived from an acid anhydride is used. It is preferable to use, for example, stainless steel, Hastelloy, Monel, Inconel, titanium, titanium alloy, dinoreconium, dinoreconium alloy, nickel, -nickel alloy, tantalum, or fluororesin, or a material coated with various types of glass on the inside. Can be illustrated.

The regenerated acid can be used as it is in the Beckmann rearrangement reaction with the above-mentioned catalyst system, and the regenerated acid can be converted to an acid anhydride by a method described later.

(3) Step of dehydrating and condensing the regenerated acid to regenerate the acid anhydride

The acid regenerated in the above step (2) or the acid separated from the amide compound and the starting oxime compound without passing through the neutralization step is then converted to an acid anhydride by dehydration condensation. . The dehydration-condensation reaction is usually performed by reacting with a dehydrating agent. As the dehydrating agent, carboxylic acid anhydride, fuming sulfuric acid, diphosphorus pentoxide, condensed phosphoric acid, more preferably carboxylic acid anhydride, phosphorus pentoxide Is used.

Hereinafter, the case where sulfonic acid is converted to sulfonic anhydride using carboxylic anhydride will be described in detail.

Commonly used methods for producing sulfonic anhydride include a method in which the corresponding sulfonic acid is dehydrated with dicyclohexylcarbodiimide チ thionyl chloride, diphosphorus pentoxide, or the like.- Toluenesulfonic acid and diphenyl Mercury and tributylphosphine Is mixed with benzene in benzene and heated to obtain _p -toluenesulfonic anhydride together with mercury and triptylphosphine oxide (T. Mukaiyama, I. Kuwajima, Z. Suzuki, J. Org Chem., 28, 2024 (1963)), a method in which methoxyacetylene and p-toluenesulfonic acid are reacted in methylene chloride to obtain p-toluenesulfonic anhydride together with methyl acetate (G , E glinton, ERH Jones, BL Shaw, MC Whiting, J. Chem. Soc., 1860 (1954)), p-tonoreensnolefonic acid reacts with succinic acid dichloride. , P-Toluene anhydride together with succinic anhydride and hydrogen chloride (MH Karger, Y. Mazur, J. Org. Chem., 36, 528 (1971)), benzenesulfone A method of synthesizing silver acetate by heating to reflux in acetyl chloride, filtering and distilling at 100 ° C-0.1 mmHg (W. F 1 a V e 11, NC Ross, J. Chem. Soc., 5474 (1964)), and methanesulfonate and acetyl chloride are mixed and heated to reflux, and excess acetyl chloride is removed by distillation to remove methanesulfonic anhydride. Methods for obtaining goods (MH K arger, Y. Mazur, J. Org. Chem., 36, '5 28 (1 9 71)) have been proposed, but these are economical problems. It has difficulty in operability, etc., and is not always satisfactory as an industrial production method.

In addition, acetyl p-toluenesulfonate, a mixed acid anhydride that can be synthesized from p-toluenesulfonic acid and acetic anhydride, is relatively easily decomposed (3.0 ° C 12 h) in the presence of a small amount of dimethyl ether, and almost Reported that it was completely disproportionated to p-toluenesulfonic anhydride and acetic anhydride.Similarly, acetyl methanesulfonate, which can also be synthesized from methanesulfonic acid and acetic anhydride, was synthesized from acetoyl sulfide and methanesulfonic acid. In this process, methanesulfonic anhydride was successfully obtained in a yield of about 50% by shortening the reflux time and distilling as it was at 120 ° C-10-3 mmHg (both by MH Karger). , Y. Mazur, J. Org.Chem., 36, 528 (1971)) However, all of them have problems such as a very long reaction time, a distillation process at high temperature and high vacuum, and the influence of acetic acid during the reaction or the necessity of removing it. No reference was made, and non-quantification that acetyl paratoluenesulfonate was almost completely disproportionated in the presence of the above-mentioned traces of dimethyl ether due to a lack of understanding over the whole process of the reaction and a lack of optimization of the reaction. In all cases, the yields are low except where noted.

Furthermore, regarding the latter reaction in the literature, the disproportionation of acetyl methanesulfonate to methanesulfonic anhydride and acetic anhydride is considered only as a reaction catalyzed by the acid methanesulfonic acid, Nothing is said about the 1: 1 correspondence reaction between sulfonic acid and sulfonic acid, nor is there any mention of reducing the chromogenic impurities caused by exposure to high temperatures during distillation.

In addition, as a method for purifying the crude sulfonic anhydride, generally, a method in which a crude sulfonic anhydride containing impurities is poured into ice water or cold water to recover a sulfonic anhydride which is hardly soluble in water, Method of Recrystallization and Recovery from Various Solvents' (W..F1a Vel1, NC Ross, JChem.Soc., 5474 (1964), N.H.C hristensen, A cta C he m. S cand., 1 5, 2 1 9

(1 96 1)), distillation purification, washing with solvent (NHChrisstensen, ActaChem. Scand., 15, 1507 (19661), NHChristensen) , A cta C he m. S c. An d., 1 5, 2 1 9 (1 9 6

1)) etc. have been proposed.

However, the conventionally proposed recovery, recrystallization, and solvent washing in water were not effective purification methods from the viewpoints of workability, safety, and economy. Generally, in addition to unreacted sulfonic acids and mixed acid anhydrides, by-products such as organic acids and organic acid anhydrides, and trace amounts of color-forming properties and polymeric substances are contained as impurities. And many.

In this step, in view of the above-mentioned problems of the prior art, sulfonic acid and inexpensive carboxylic acid anhydride can be mixed without using an expensive dehydrating agent or reaction reagent. Remove by-products or residual carboxylic acids and carboxylic anhydrides from the system It has been found that the sulfonic anhydride can be obtained easily and economically by performing the above reaction.

In addition, the purification method of the synthesized sulfonic anhydride does not involve the inefficient operation of recrystallization or the complicated procedure of continuous washing with several types of solvents. Even with sulfonic anhydride, it was found that high-purity sulfonic anhydride can be recovered more easily, safely, and economically by rinsing with an inexpensive aprotic washing solvent2. Was.

In this step, the reaction for producing sulfonic anhydride from sulfonic acid is represented by the following formula

It is as (1). In this example, p-toluenesulfonic acid is used as the raw material sulfonic acid and acetic anhydride is used as the carboxylic acid anhydride. Ii) Toluenesulfonic anhydride.

(P)

(1) First, p-toluenesulfonic acid (A) and acetic anhydride (B) react to form a mixed acid anhydride (C) as an intermediate product. At this time, acetic acid (D) derived from acetic anhydride is produced as a by-product. After the mixed anhydride (C) is formed, either of the following two methods (1) and (2) can be used to obtain p-toluenesulfonic anhydride (E) .

(1) A method in which a mixed acid anhydride (C) is converted to p-toluenesulfonic anhydride (E) by a disproportionation reaction (1).

(2) A method in which the mixed acid anhydride (C) is further reacted with p-toluenesulfonic acid (A) to obtain p-toluenesulfonic anhydride (E) by the reaction of (second stage _2). In this case, p-toluenesulfonic acid (A) itself has catalytic activity for the disproportionation reaction of acetyl p-toluenesulfonate (C), which is an intermediate (11), so acetic anhydride (B) is used. The reaction in the latter stage 11 can be allowed to proceed sufficiently while removing it outside.

By controlling the amount of acetic anhydride used, the reaction method (1) or (2) can be adopted.

If the charged acetic anhydride (B) is sufficiently high, almost all of the charged p-toluenesulphonic acid (A) will be an intermediate (C) after mixing at 25 ° C. In that case the intermediate (C) is disproportionated and is the desired product! 1) Toluenesulfonic anhydride (E) is obtained (1). (Method (1))

If the amount of acetic anhydride (B) charged is relatively small compared to the amount of p-toluenesulfonic acid (A), extra p-toluenesulfonic acid (A) will remain in the system after the intermediate is formed. Therefore, the mixed acid anhydride (C), which is an intermediate, reacts with another molecule of p-toluenesulfonic acid (A) to form ρ-toluenesulfonic anhydride (E) and acetic acid (D). (2). In this case, p-toluenesulfonic acid (A) catalyzes the reaction (11). (Method (2))

In the case of (1), where the amount of acetic anhydride (B) charged is large, p-toluenesulfonic anhydride (E) can be obtained with very high yield and high purity, but it is usually 85 ° C to 120 ° C. Since high temperature and reduced pressure are required, impurities due to high temperature are generated, and the product usually appears black. I do.

In the case of (2), in which the amount of acetic anhydride (B) in the preparation was reduced, the acetic acid (D) produced as a by-product was removed out of the system by reducing the pressure even at a low temperature of, for example, 60 ° C. By proceeding with the reaction of the latter stage 1), the desired product p-toluenesulfonic anhydride (E) can be synthesized while suppressing the generation of chromogenic impurities, although the yield is low. .

The reasons why the sulfonic anhydride can be synthesized in high yield in this step and the reason why the low-temperature production method is effective in reducing impurities in the sulfonic anhydride are not necessarily clear. However, it is estimated as follows.

First, both the first and second reactions ((1) and (2)) are considered to be equilibrium reactions. Therefore, acetic acid (D) (or acetic anhydride) by-produced in the reaction system

(B)), removing p-toluenesulfonic anhydride (E), which is the target substance, from the system allows the reaction to proceed further. In this case, specifically, acetic acid or acetic anhydride can be removed from the system by reduced pressure, and p_toluenesulfonic anhydride can be removed from the system by crystallization.

As for the color-forming impurities in the high-temperature reaction, the mixed acid anhydride as an intermediate

When (C) is exposed to high temperatures, it decomposes into p-toluenesulfonic acid (A) and ketene, which is considered to be a small amount of ketene polymer-derived substances produced at that time. Therefore, by making use of the equilibrium characteristics of the reaction and performing the reaction at the lowest possible temperature, it is possible to obtain a light-colored _p -toluenesulfonic anhydride (E) while suppressing the generation of impurities.

(Sulfonic acid)

The sulfonic acid used in this step is not particularly limited as long as it is derived from the sulfonic anhydride used in the Beckmann rearrangement reaction of the present invention. Two or more sulfonic acids can be used as the sulfonic acid. In addition, an asymmetric sulfonic anhydride can be obtained by producing a mixed anhydride of sulfonic acid and carboxylic acid and then reacting with another type of sulfonic acid.

(Carboxylic anhydride)

The carboxylic anhydride used in this step is not particularly limited, Specifically, in addition to linear aliphatic carboxylic acids such as acetic anhydride, propionic anhydride, butyric anhydride, isobutyric anhydride, and cyclohexylacetic anhydride, maleic anhydride, succinic anhydride, and hexahexanedicarboxylic acid Examples thereof include aliphatic carboxylic anhydrides which have become cyclic by intramolecular dehydration of anhydrides and the like, and various aromatic carboxylic anhydrides such as phthalic anhydride and benzoic anhydride. Further, in all of these carboxylic anhydrides, a hydrogen atom on carbon in the molecule may be substituted by a halogen atom, an acyl group, an alkoxy group or the like.

In this step, an acid anhydride can be effectively obtained by removing the by-produced carboxylic acid, carboxylic anhydride and target sulfonic anhydride from the system. For this reason, the sulfonic acid anhydride and the sulfonic acid anhydride should be removed so that at least one of the carboxylic acid derived from the carboxylic acid anhydride, the carboxylic acid anhydride, and the target sulfonic anhydride can be removed out of the system in the reaction process. Therefore, it is important to appropriately select the sulfonic acid and the desired sulfonic anhydride in consideration of the combination so that the product and the carboxylic acid and the carboxylic anhydride can be separated. Among them, those having a boiling point of 300 ° C. or less at normal pressure, preferably hydrated acetic acid, are preferably used, and the carboxylic acid formed by hydrolyzing the sulfonic acid anhydride and the carboxylic acid anhydride is preferably used. ·

The amount of the sulfonic acid anhydride used in this step is not particularly limited, but is 0.1 to 50 equivalents to the sulfonic acid. The amount of carboxylic anhydride used varies depending on the method employed as described above. In the case of synthesizing sulfonic anhydride with high yield and high purity by the method (1), the amount of carboxylic anhydride is used in the range of 1 to 25 equivalents, preferably 1 to 10 equivalents. You. When it is desired to proceed the reaction with low selectivity by the method (2) at a low temperature, 0.1 to 3 equivalents, preferably 0.25 to 1.5 equivalents, more preferably 0.2. It is used in the range of 5 to 1 equivalent.

If the amount is less than these ranges, a sufficient yield of sulfonic anhydride cannot be obtained. On the other hand, if the amount is too large, the holding amount in the reactor increases and the economic effect decreases. Further, in the method (2), if the amount of the carboxylic acid anhydride is excessively larger than the above amount, most of the charged sulfonic acid easily mixes with the sulfonic acid and the carboxylic acid at the beginning of the reaction. It becomes a mixed acid anhydride, and the reaction of (second stage 1) and the reaction of (second stage 1) catalyzed by sulfonic acid do not proceed, and the disproportionation reaction from the mixed acid anhydride of (1) proceeds .

(Solvent or additive)

In the sulfonic anhydride synthesis reaction in this step, it is preferable not to use any reaction solvent or additive other than the carboxylic anhydride having the function as a reactant from an economical viewpoint. Possible additives or solvents include, for example, aliphatic hydrocarbon compounds such as n-hexane, n-heptane, n-octane, n-dodecane, benzene, toluene, xylene, mesitylene, monochrome benzene, methacrylate Aromatic hydrocarbon compounds such as xylene, acetonitrile, propane etrile, force proethanole, adipole ^ /, benzonitrile, tonole nitrile, etc. Ester compounds such as methyl acetate, dimethyl ether Jefferies Chirueteru, diglyme, ether compounds such as tetrahydrofuran, methylcarbamoyl Ren chloride, black hole Holm, halogenated alkyl compound of dichloroethane, Jimechinore formamide, 1, 3-dimethyl-2-amide compounds such Imidazorijinon the like. Among them, ethers such as tetrahydrofuran, nitriles such as acetonitrile, and alkyl halides are preferable in terms of reaction. These may be used alone or in combination.

(Reaction conditions)

In this step, the method for removing by-product carboxylic acid is not particularly limited, and specifically, 1) a method of distilling off under reduced pressure, 2) a gas that is inert or has no adverse effect on the reaction. And 3) crystallization.

These removal methods may be used alone or in combination. It is also preferable to remove the residual carboxylic acid anhydride or the target product, sulfonic anhydride together with the carboxylic acid, if necessary.

The concentration of the carboxylic acid in the system after the reaction is preferably not more than a certain value, specifically, 10%, more preferably 5% or less as a weight percentage in the reaction product. preferable.

The pressure at which carboxylic acid or carboxylic anhydride is distilled off under reduced pressure may be lower than atmospheric pressure, but is preferably 0.01 Pa to 99000 Pa, more preferably 0.05 Pa to It is 50000 Pa, and furthermore, 10 to 50000 Pa. When the carboxylic acid is removed by distillation under reduced pressure, the boiling point of the sulfonic acid as a reactant, the mixed acid anhydride as an intermediate, and, if possible, the carboxylic acid to be removed from the target sulfonic acid anhydride is reduced. Since it needs to be low, the carboxylic anhydride of the substrate is selected in consideration of the boiling point of these alone or in the mixture.

Inert gases used when carboxylic acid is passed through a gas that is inert or has no adverse effect on the reaction and is entrained in the reaction are, for example, argon, helium, neon, nitrogen, methane, and ethane. , Propane, or a mixed gas thereof.

In the case of co-evaporation with gas, the sulfonic acid as a reactant and the mixed anhydride as an intermediate and, if possible, the target sulfonic anhydride should be removed, since the volatility of the carboxylic acid needs to be high. The carboxylic anhydride of the substrate is selected taking into account the volatility of these alone or of the mixture. -When carboxylic acid is removed by crystallization, there are methods such as lowering the temperature for crystallization in the middle of the reaction and adding a poor solvent. In the case of removal from the system by crystallization, it is necessary that the melting point of the sulfonic acid, which is the reactant, and the mixed acid anhydride, which is the intermediate, and, if possible, the melting point of the carboxylic acid to be removed is higher than that of the target sulfonic anhydride, The carboxylic anhydride of the substrate is selected in consideration of the melting point of these alone or the mixture. When a poor solvent is used, the sulfonic acid as a reactant, the mixed acid anhydride as an intermediate, and the carboxylic acid to be removed from the target sulfonic acid anhydride, if possible, are added to the solvent to be used. The carboxylic anhydride of the substrate is selected so that the solubility is low.

In this step, "reaction is performed while removing by-produced carboxylic acid" means that an operation for removing carboxylic acid is added at any point during the reaction. In addition to the operation for removing the acid, the operation for removing the carboxylic acid may be performed intermittently. In a preferred embodiment of this step, the desired sulfonic anhydride is obtained without isolating the mixed acid anhydride obtained as an intermediate product during the reaction. By removing sulfonic acid and carboxylic acid anhydride out of the system, the mixed acid anhydride is finally consumed, so that it is easier to operate without isolation. Good yield and high selectivity can be achieved.

In another preferred embodiment of this step, the reaction is carried out substantially without a solvent. Substantially solvent-free does not prevent the presence of an inert gas or solid in the reaction system as long as it has no adverse effect on the reaction and does not substantially reduce the concentration of the substrate. Specifically, it means that the solvent substance other than the substrate and the reaction product in the reaction mixture is 10% or less, preferably 5% or less by weight percentage. By eliminating the use of a solvent, the substrate concentration can be increased, the reaction speed is increased, and the post-reaction treatment is simplified. In the case of this reaction, good yield and selectivity can be achieved without using a solvent.

The conditions for carrying out this step are not particularly limited, but the reaction temperature is usually 0 ° G to 250 ° C., preferably 10 ° C. to 130 ° C., more preferably 15 ° C. to 12 ° C. It is performed in the range of 0 ° C. The reaction pressure is not particularly limited, and the reaction is carried out under reduced pressure to increased pressure. It is preferably carried out under reduced pressure to normal pressure. More preferably, it is carried out under reduced pressure of 500 Pa or less. It is also preferable to carry out the reaction while passing an inert gas or the like irrespective of the reaction pressure. Further, the reaction time is usually 5 minutes to 30 hours, preferably 10 minutes to 15 hours, including the temperature raising step and the pressure reducing step.

In this step, the reaction proceeds regardless of whether sulfonic acid or carboxylic anhydride is charged into the reactor first. In addition, the reaction proceeds even when one of them is heated to a predetermined temperature first, and then the other is added. Furthermore, when the reaction is carried out by a combination of heating and depressurization and gas flow, the reaction proceeds regardless of which combination is selected. The reaction can proceed even if the persons are started simultaneously.

The type of reaction in this step is not particularly limited, and may be a batch reaction or a continuous flow. Any of the reactions can be performed. The type of the reactor is not particularly limited, and a general reactor such as a reactor having one or two or more continuous stirring tanks or a tubular reactor can be used.

In the present invention, an acid anhydride or an acid derived from an acid anhydride, another acid for regenerating an acid derived from the acid anhydride, a carboxylic anhydride and a carboxylic acid are used. For example, stainless steel, Hastelloy, Monel, Inconel, Titanium, Titanium alloy, Zirconium, Zinoleco-Pem alloy, Nickel, Nickel alloy, Tantalum, or fluororesin, or various kinds of glass are coated inside. Examples of such materials include: · The sulfonic acid, carboxylic anhydride and reaction solvent used in this reaction are preferably subjected to sufficient water removal in advance before the reaction. 'It is desirable that the operation during the process be performed in a dry atmosphere.

The reaction format of this step will be described below with reference to an example of a batch reaction.

The sulfonic anhydride and carboxylic anhydride are supplied to the reactor together with a solvent as required, and the reaction is carried out at a predetermined temperature and a predetermined pressure for a desired time. And the reaction mixture containing carboxylic anhydride. If the sulfonic anhydride can be separated as a solid from these reaction mixtures, the sulfonic anhydride can be filtered off by filtration. In this case, if the filtrate contains sulfonic acid, sulfonic anhydride, or a mixed acid anhydride of sulfonic acid and carboxylic acid, the sulfonic acid anhydride or the mixed acid anhydride of sulfonic acid and carboxylic acid is filtrated. After separation from the acid anhydride, it can be reused again in the acid anhydride process.

The reaction product can be recovered as a sulfonic anhydride having considerably high purity by suitably selecting the reaction conditions. If carboxylic acid, carboxylic anhydride, or trace amounts of color-forming or polymeric substances are present as impurities in addition to unreacted sulfonic acids and mixed acid anhydrides in sulfonic acid anhydride, if necessary It is also possible to purify by distillation, crystallization, washing and extraction.

Even in such an acid anhydride reaction, if the acid contains an amide compound or an unreacted oxime compound, the yield of the regeneration reaction is reduced. Therefore, it is preferable to reduce the number of moles of the amide compound or unreacted oxime compound to 0.2 or less, more preferably 0.1 or less, and further preferably 0.05 or less per mole of the acid.

Further, the obtained acid anhydride can be recycled to the Beckmann rearrangement reaction step.

(Purification method of regenerated acid anhydride)

When the obtained sulfonic anhydride contains impurities as described above, it is preferable to carry out purification by washing with an aprotic solvent.

As a preferred embodiment of this step, in the method for purifying the crude sulfonic anhydride, the sulfonic anhydride is a sulfonic anhydride used in the Beckmann rearrangement reaction, and the washing solvent is a carboxylic anhydride, a carbonate, It is an aprotic and relatively low-boiling organic solvent represented by nitrile compounds, ethers, carboxylate esters, nitro compounds, halogenated hydrocarbons, etc., and more preferably acetic anhydride. It can be mentioned that. ·

In another preferred embodiment of the present step, in the method for purifying the crude sulfonic anhydride, the amount of the target sulfonic anhydride dissolved in 1 g of the washing solvent is adjusted to the atmospheric pressure at the temperature at which the washing operation is performed. Below 0.0001 g to 10 g, the washing solvent used in the range of 0.5 to 200 equivalents to the amount of sulfonic anhydride in the crude sulfonic anhydride, and the washing operation temperature Is below 200 ° C.

Further, the weight percentage (purity) of the sulfonic anhydride in the crude sulfonic anhydride is preferably 3% to 99.999%, and the sulfonic anhydride in the finally obtained sulfonic anhydride is preferably used. It is characterized in that impurities are contained in a total concentration of 1% to 5% by weight, and the purity of sulfonic anhydride per weight is 95% to 99.999%.

(Sulfonic anhydride)

The sulfonic anhydride used in this step is not particularly limited as long as it can be used in the Beckmann rearrangement reaction of the present invention. Considering the efficiency of the rinsing operation, the sulfonic anhydride is preferably solid at the temperature at which the rinsing operation is performed. Therefore, the melting point of the sulfonic anhydride is preferably 150 ° C. or more, more preferably 0 ° C. to 300 ° C.

(Wash solvent)

The washing solvent used in this step includes aprotic and relatively low boiling points such as carboxylic acid anhydride, carbonate, nitrile compound, ether, carboxylic acid ester, nitroylide compound, and halogenated hydrocarbon. Organic solvents are preferably applied. In these organic solvents, all hydrogen atoms on carbon in the molecule may be substituted by halogen atoms or other substituents. Also, a mixed solvent obtained by combining these solvents can be suitably used.

When these washing solvents are applied to the present invention, they must be liquid at each operating temperature.

It is also important to select an appropriate solvent in consideration of the combination with the sulfonic anhydride so that the trace solvent remaining after the washing can be easily removed from the target sulfonic anhydride after the fact.

When the residual solvent is removed by distillation after washing, a solvent having a boiling point of usually 250 ° C. or lower is preferable. More preferably, a solvent having a boiling point of 200 ° C. or lower is selected, and more preferably, a solvent having a boiling point of 150 ° C. or lower is selected. For example, acetic anhydride (boiling point 140 ° C), propylene carbonate (boiling point 240 ° C), acetutrile (boiling point 81 ° C to 82 ° C), benzonitrile (boiling point 191 ° C), THF (Boiling point 65 ° C to 67 ° C), methyl formate (boiling point 34 ° C) and the like are preferred. Further, from the viewpoint of ease of operation, a solvent having a boiling point of 10 ° C or more is preferable, and a solvent having a boiling point of 30 ° C or more is more preferable.

The amount of the washing solvent used in this step is not particularly limited, but is generally about 0.5 to 200 equivalents, preferably 0 to 200 equivalents to the amount of sulfonic anhydride in the crude sulfonic anhydride. It is used in the range of 8 to 100 equivalents, more preferably 1 to 80 equivalents. If the amount is less than this range, sufficient washing cannot be performed.On the other hand, if the amount is too large, the amount of hold in the purification system increases, which reduces the economic effect and often dissolves in some solvents. Therefore, the yield of sulfonic anhydride is reduced. (Mixing of solvents or additives)

In the crude sulfonic anhydride purification step of this step, it is preferable not to use an additive from an economic viewpoint, and it is not particularly necessary to use a mixed solvent as a washing solvent. Anhydrides, carbonates, nitrile compounds, ethers, carboxylate esters, nitro compounds, halogenated hydrocarbons and the like can be used in combination. The mixing method-order-ratio is not particularly limited.

(Purification conditions)

In the purification method of this step, the crude sulfonic anhydride is rinsed with a solvent. Rinsing is an operation in which a solvent is once brought into contact with a crude sulfonic anhydride and then the solvent is removed from the sulfonic anhydride, and the method is not particularly limited. An operation in which the anhydride is placed in a filter and the solvent is directly sprinkled thereon, or an operation in which the crude sulfonic anhydride and the solvent are mixed in a vessel and the sulfonic anhydride is removed by filtration, is exemplified. In the case of industrial implementation, the washing method is not particularly limited.For example, a method in which a washing solvent is put into a container having crude sulfonic anhydride in a fixed bed form from the bottom, and then the solution is simply removed by filtration. Or a method of sprinkling in the form of a shower from above and filtering, a method of charging the solvent and the crude sulfonic anhydride in the same container, stirring and washing the slurry with stirring blades, and then filtering. .

Further, in order to efficiently remove impurities from the crude sulfonic anhydride, it is preferable to first grind the crude sulfonic anhydride containing impurities into fine particles before rinsing with a solvent. The technique is not particularly limited, but one suitable technique is to add a small amount of a solvent to be used for washing in advance, and then physically mix and pulverize. In this case, either the solvent or the crude sulfonic anhydride may be charged into the container first. Purification can be performed, for example, by pulverizing and filtering, and then sprinkling a solvent directly on the sulfonic anhydride recovered as a filtration residue. According to the purification method of this step, the weight of the sulfonic anhydride in the crude sulfonic anhydride depends on the type of the sulfonic anhydride and the method adopted. Even if the percentage (purity) is extremely low, such as 10% or 20%, it is possible to purify into high-purity sulfonic anhydride.

Depending on the purification conditions, a small amount of the washing solvent used for the sulfonic anhydride immediately after the purification may be attached or mixed, but this residual solvent may be removed by drying at normal temperature and normal pressure. Alternatively, it may be placed under a flow of a dry gas inert to the chemicals used, or may be forcibly evaporated or distilled off by heating or reducing the pressure. The pressure for the distillation under reduced pressure may be lower than the atmospheric pressure, but it is necessary to set the degree of reduced pressure in consideration of the boiling point of the sulfonic anhydride. When removing the residual washing solvent by distilling off under reduced pressure, the boiling point of the target sulfonic anhydride must be taken into consideration, since the boiling point of the cleaning solvent to be removed must be lower than that of the target sulfonic anhydride. To select a washing solvent. Conversely, when it is preferable to use a washing solvent having a boiling point higher than the boiling point of the sulfonic anhydride, the sulfonic anhydride can be separated by distillation. When the solvent is distilled off by heating, a washing solvent having a boiling point that allows sufficient distillation at a temperature at which the target sulfonic anhydride is not decomposed should be selected.

Further, as a gas used in the case of passing an inert gas having no adverse effect on the purification step and performing co-evaporation, for example, argon, beryde, neon, nitrogen, methane, ethane, propane, or These mixed gases can be mentioned.

In this case, too, it is necessary that there is a difference between the volatility of the target sulfonic anhydride and the residual cleaning solvent to be removed. Therefore, the cleaning solvent is selected in consideration of the volatility of the target sulfonic anhydride.

If the solvent after washing contains a sulfonic acid or a mixed anhydride of a sulfonic acid and a carboxylic acid, separate the solvent from the solvent as necessary, and then remove the mixed anhydride of the sulfonic acid or the mixed anhydride of the sulfonic acid and the carboxylic acid. It can be reused in the acid anhydride conversion step. In another preferred embodiment of the purification method of the present step, all the purification steps are carried out in the presence of a dry inert gas having no adverse effect. However, if the combination of sulfonic anhydride and the washing solvent does not cause any adverse effects such as oxygen and moisture, etc., that will alter the target sulfonic anhydride, operate in an open system. Is also possible.

In addition, an inert solid can coexist in the system throughout the purification process.

The conditions for carrying out the present purification step are not particularly limited, but the temperature is usually 200 ° C or lower, preferably 100 ° C to 100 ° C, more preferably 0 ° C to 50 ° C. It is implemented in the range of. When dealing with a substance having a low melting point, such as trifluoromethanesulfonic anhydride, it is preferable to set the temperature at the time of purification sufficiently low so as to be a solid. In this case, a solvent used as a washing solvent at the purification temperature is appropriately selected. The pressure in the purification step is not particularly limited, either, and it is carried out under reduced pressure to increased pressure depending on the type of the sulfonic anhydride and the washing solvent used, and the method employed. Steps other than the final separation step between the residual washing solvent and the purified sulfonic anhydride are preferably carried out under normal pressure to slight pressure.

The purification format for carrying out the purification in this step is not particularly limited, and it can be carried out by either a batch system or a continuous flow system. There is no particular limitation on the type of vessel used to grind the solid crude sulfonic anhydride, and an ordinary vessel can be used. Since an acid is used in the present invention, it is preferable to use a corrosion-resistant material for the vessel, for example, glass, stainless steel, Hastelloy, Monel, Inconel, titanium, titanium alloy, zirconium, zirconium alloy, nickel, Examples include Eckel alloys, tantalum, or fluororesins, and materials coated with various types of glass on the inside.

(Separation of amidated ^^ compounds and catalyst components when oxime hydrochloride is used as oxime raw material, regeneration method of catalyst components)

When oxime hydrochloride is used as a raw material for oxime, the target amide compound and the catalyst component can be separated, purified, or regenerated respectively by the following method, for example.

That is, the hydrochloride of the amide compound is crystallized and separated by, for example, partially distilling off the solvent or adding a poor solvent as necessary, and recovering the catalyst component in the filtrate. When the hydrochloride of the amide compound is partially contained in the filtrate, the catalyst component or the hydrochloride of the amide compound is used. Either one is removed by a known operation such as extraction, crystallization, or distillation, and the catalyst component and the hydrochloride of the amide compound are separated. For example, a method of extracting the catalyst component by distilling off the solvent from the filtrate and then adding a solvent that selectively dissolves only the catalyst component (for example, toluene in the case of P-toluenesulfonic acid) can be adopted. .

The separated hydrochloride of the amide compound is transported together with the hydrochloride of the crystallized amide compound to a known separation and purification step (for example, a thermal decomposition step or a decomposition step by adding water) to form the amide compound and hydrochloric acid. It is purified after being decomposed. The recovered hydrochloric acid can be recycled to the process for producing oxime hydrochloride, or can be recycled to the cycloalkanone photolithography process.

The recovered catalyst component can be converted to an acid anhydride in the above (step of dehydrating and condensing the regenerated acid to regenerate the acid anhydride).

On the other hand, in the case where the Beckmann rearrangement reaction is carried out using oxime hydrochloride as an oxime raw material without using an acid anhydride, there is no need to separate the catalyst components. In this case, if necessary, the solvent is partially distilled off, the hydrochloride of the amide compound is separated by crystallization filtration, and the solvent and light-boiling by-products are recovered in the filtrate. The separated hydrochloride of the amide compound is carried to a known separation / purification step (for example, a thermal decomposition step or a decomposition step by adding water) ′, and is decomposed into an amide compound and hydrochloric acid. The amide compound is purified, if necessary, by a known purification method. The recovered hydrochloric acid can be recycled to the process of photo-trosation of cycloalkanone, which is recycled to the process for producing oxime hydrochloride. The recovered solvent is distilled appropriately after removing light boiling by distillation, and is then circulated to the Beckmann rearrangement step.

It has been known that when these oxime hydrochlorides are subjected to Beckmann rearrangement in a toluene solvent as an oxime compound in the method of the present invention, the solvent is conventionally altered (Japanese Patent Publication No. 52-17). 0 34, Japanese Patent Publication No. 52-170,35, Japanese Patent Publication No. 44-79,338). In addition, there has been concern that impurities derived from deterioration of the solvent may be mixed into the amide compound of the product, thereby deteriorating the product quality. In the present invention, amide (acetamide in the case of aceto-tolyl solvent) which is a by-product derived from the solvent, which has been supposed to be formed by the reaction with oxime hydrochloride and a nitrile solvent (Chem. Purrun) , 3 1 (1 98 1) 250., The production of Tokubiko 49-8 7687) can be greatly reduced.

Also when using oxime hydrochloride in this way, it is desirable to use a corrosion-resistant reactor as mentioned above. Examples>

Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples unless it exceeds the gist thereof.

The following amide compounds in the examples (Ratatamu) yield in mole ^_0/0 against the charging Okishimu, TON values (Turn Over Number) are expressed in moles of the product lactam against sulfonic anhydride charged.

Ratatam yield and TON were determined by iH-NMR unless otherwise specified. When insoluble catalyst is present, dichloromethane is used as the internal standard, and the integral ratio of methylene (CH ₂ ) adjacent to L-H or C = 0 of the lactam (2H) and the integral of dichloromethane with pro-ton It was calculated from the ratio (2H).

When all of the catalyst was dissolved, the amount of ratatum produced was determined based on hydrogen (2H) in the benzene nucleus of p_toluenesulfonic acid.

The conversion of the oxime compound was determined by the mole% of all the products based on the sum of the remaining oxime compound and all the products, and the selectivity of lactam and ketone was determined by the mole% of each product relative to the total products. Reference Example 1 (Synthesis of cyclododecanone oxime)

Cyclododecanone oxime was synthesized because there is no commercial product. An example of the synthesis method is shown below.

Cyclododecanone (19.04 g, 0.104mo1) was charged into a flask having four ports equipped with a mechanical stirrer and a thermometer, and ethanol (164 g) was added, and the mixture was stirred at room temperature and dissolved. . Dissolve 18.07 g (0.220 mol) of sodium acetate and 10.67 g (0.065 Omo 1) of hydroxylamine sulfate in 52 ml of water. The dissociated aqueous solution was added dropwise to a solution of dodecanonone oxime in ethanol with sufficient stirring at room temperature. During the dropwise addition, the temperature of the reaction solution rose to 33 ° C. After sufficiently stirring for 3 hours at room temperature, after confirming that no cyclododecanone remained by — 丽 R analysis, ethanol ′ was distilled off at 40 ° C. under reduced pressure. 195 ml of water was added, the white solid was washed, filtered, and then washed with 40 Om1 of water. Demineralized water was added to the white solid, and the mixture was heated and stirred at 90 ° C, filtered, and washed with 90 ° C demineralized water. Ethanol was added to the washed white solid, and the mixture was dissolved by heating. After hot filtration, the crystals were recrystallized from a mixed solvent of ethanol (300 g) and water (112 g) and filtered under reduced pressure to obtain crystals. . The crystals were washed with a mixed solvent of ethanol (74 g) and water (28 g) at 0 ° C on a filtration bell of a reduced pressure filter, filtered under reduced pressure, and further air-dried for 1.5 hours to obtain cyclododecanone oxime. At this time, the water content of cyclododecanone oxime was 11.3 wt. /. Met. '

For the following dodecanonone oximes in Examples and Comparative Examples, crystals obtained by such a method were appropriately dried under reduced pressure. According to this method, dodecanonone oxime can be obtained at a yield of about 9 Omo 1% based on the charged dodecanone.

In addition, the analysis of the water content of the preparation in the following Examples was calculated from the water content of cyclododecanone oxime and the reaction solvent. The water content after the reaction was analyzed for the reaction solution as it was. The water content was analyzed by the Karl Fischer method (coulometric titration method), and the anolyte was Aquamicron AX (manufactured by Mitsubishi Chemical) and the catholyte was Aquamicron CXU (manufactured by Mitsubishi Chemical). The water content of cyclododecanone oxime was analyzed as a solid in a dry atmosphere, poured into an anolyte in a moisture measurement device, and dissolved in the anolyte. Example 1

In a 50 ml round-bottomed flask dried in a dryer at 70 ° C., there was added 10.0755 g (5.06 mmo 1) of dodecanonone oxime having reduced water content to 715 ppm by vacuum drying, and 40.1 g of toluene previously dried with molecular sieve 3A (Water content 8 ppm) was charged under an argon atmosphere. After heating to 95 ° C in an argon atmosphere to dissolve cyclododecanone oxime, 0.2185 g (0.6695 mmo1) of p-toluenesulfonic acid anhydride and 2.5 g of toluene were mixed. The mixture was added (most of p-toluenesulfonic anhydride was not dissolved in toluene), and the mixture was heated and stirred at 95 ° C to perform a Beckmann rearrangement reaction.

Even under reaction conditions, most of! ) The monotoluenesulfonic anhydride was not dissolved in the solvent but was dispersed in the solvent.

The reaction solution was sampled as a hot solution and analyzed by iH-NMR. As a result, the yield of ω-laurin lactam after 0.5 hour was 12.7 ° / ₀ , and the ΤΟΝ value was 9.7.

The TONs after 1.0 hour, 1.5 hours, 2.0 hours, and 2.5 hours were 25.8, 32.5, 33.2, and 34.6, respectively, and a tendency to gradually increase was observed. Was. The molar ratio of the total amount of water contained in cyclododecanone oxime and toluene before the start of the reaction to P-toluenesulfonic anhydride was 0.63. Comparative Example 1 '

Cyclododecanone oxime synthesized in the same manner as in the Reference Example was filtered under reduced pressure and air-dried until further. At this time, the water content was 1.89 wt% '. Beckmann rearrangement of cyclododecanone oxime was performed in the same manner as in Example 1 except that the reaction atmosphere was not replaced with this cyclododecanone oxime and toluene manufactured by Junsei Chemical Co., Ltd. (water content: 118 ppm). went. Again, most of the! ) Toluenesulfonic anhydride did not dissolve in 2.5 g of toluene.

The reaction solution was similarly analyzed by iH-NMR. As a result, the yield of ω-laurinlactam was 0.5% in 0.5 hours, and the TON value was 0.4. The TON value after 1.0 hour was 0.7, and no remarkable increase was observed.

Before the start of the reaction, the molar ratio of the total amount of water contained in dodecanonone oxime and toluene to p-toluenesulfonic anhydride was 15.9. Example 2 Under an atmosphere, cyclododecanone oxime 10.050 g (50.98 g) was dried in a 50 ml round bottom flask dried at 70 ° C. under reduced pressure to a water content of 0.128 wt% by vacuum drying. mmo 1) and 40.0 g of acetonitrile (water content Op (below detection limit)) previously dried with molecular sieve 3A were charged. After heating to 55 ° C under an argon atmosphere, a solution prepared by dissolving 0.2206 g (0.6759 mmo 1) of p-toluenesulfonic anhydride in 2.5 g of acetoethrile was added, and the reaction was carried out with stirring. The temperature was gradually increased to 80 ° C over 3 hours to perform the Beckmann rearrangement reaction. Even under the reaction conditions, p-toluenesulfonic anhydride was dissolved in the solvent. Cyclododecanone oxime was not completely dissolved in the solvent at the start of the reaction, but was eventually completely dissolved.

The reaction solution was sampled as a hot solution and analyzed by iH-NMR. As a result, after 3 hours, the yield of ω-laurinlactam was 100%, the TON value was 76, and all dodecanonone oximes had disappeared.

Before the start of the reaction, the molar ratio of the total amount of water contained in the dodecanonone oxime and acetonitrile to p-toluenesulfonic anhydride was 1.1. Example 3

In an argon atmosphere, cyclododecanone oxam 8.00231 g (40%) was placed in a 50 ml round bottom flask dried with a dryer at 70 ° C and dried under reduced pressure to reduce the water content to 0.249 wt%. 66 mmo 1) 32.15 g (133 ppm water content) of acetonitrile manufactured by Junsei Chemical Co., Ltd. were charged. After heating to 80 ° C under an argon atmosphere, 0.1772 g (0.5429 mmo 1) of p-toluenesulfonic anhydride was dried with 2.5 g of acetonitrile (water content 0 ppm), and a Beckmann rearrangement reaction was performed with stirring. Even under the reaction conditions, P-toluenesulfonic anhydride was dissolved in the solvent. The reaction solution was sampled as a hot solution and analyzed by iH-NMR. As a result, the yield of ω-laurin lactam after 0.5 hour was 96%, and the TON value was 72. Water contained in dodecanoxoxime and acetonitrile before the start of the reaction Of the total amount, the molar ratio p- toluenesulfonic anhydride, 2 is 5, the water content of the anti応後is _{0. 04 wt% (H 2 0} / charge!) Single-toluenesulfonic anhydride = 2 (Molar ratio) H ₂ O / “total of acid and acid component corresponding to acid anhydride” = 1 (molar ratio). Example 4

A Beckmann rearrangement reaction was performed in the same manner as in Example 3 except that cyclododecanone oxime having a water content of 0.536 wt% was used.

The reaction solution was sampled as a hot solution and analyzed by iH-NMR. As a result, the yield of ω-laurinlactam after 0.5 hours was 77%, and the Δ value was 57. The TON value after one hour was 58.

The molar ratio of the total amount of water contained in cyclododecanone oxime and acetone before the start of reaction to p-toluenesulfonic anhydride was 4.7, and the water content after the reaction was 0.1 wt%. (H ₂ OZ charged p-toluenesulfonic anhydride = 5 (molar ratio) equivalent, { ₂ } / “total of acid and acid component corresponding to acid anhydride” = 2.5 (molar ratio)) . Example 5

Example 3 except that cyclododecanone oxime having a water content of 1.1 wt% and aceto ^ tolyl (water content 0 ppm (below the detection limit)) previously dried with Molecular Sieves 3 A were used. A Beckmann rearrangement reaction was performed in the same manner as in Example 1.

The reaction solution was sampled as a hot solution and analyzed by ¹ H-NMR. As a result, the yield of ω-laurinlatatam after 0.5 hours was 58%, and the Δ value was 43. The TON value after one hour was 46.

Before the start of the reaction, the molar ratio of the total amount of water contained in the dodecanonone oxime and acetone to the p-toluenesulfonic anhydride was 9.0, and the amount of water after the reaction was 0.1 lwt. % (Equivalent to H ₂ O / p-toluenesulfonic anhydride = 6 (molar ratio), H ₂₀ / “Total of acid and acid components corresponding to acid anhydride” = 3 2003/009749 ratio)). Comparative Example 2

Cyclododecanone oxime synthesized in the same manner as in the Reference Example was filtered under reduced pressure and air-dried until further. At this time, the water content was 1.71 wt ° / ₀ . 8.0 500 g (40.8 Ommol) of this cyclododecanone oxime and 32.13 g of acetotrile (purity of water: 395 ppm) manufactured by Junsei Kagaku Co., Ltd. were added to a 5 Om1 round bottom flask in air. Was charged. After heating to 80 ° C, a solution prepared by dissolving 0.1699 g (0.5206 mmo 1) of p-toluenesulfonic anhydride in 2.7 g (water content of 395 ppm) of the above-mentioned acetate was added. The Beckmann rearrangement reaction was performed with stirring. Even under the reaction conditions, p-toluenesulfonic anhydride was dissolved in the solvent.

The reaction solution was sampled as a hot solution and analyzed with iH-NMIl. As a result, the yield of co-laurin lactam after 0.5 hour was 38%, and the TON value was 30. One hour later, the yield of ω-laurin pectam was 40% and the TON value was 31, indicating no significant increase.

Before the reaction was started, the molar ratio of the total amount of water contained in the dodecanonone oxime and aceto-tolyl to ρ-toluenesulfonic anhydride was 16.1, and the water content after the reaction was 0.3 w. t% (H ₂ 0 / charge p- toluenesulfonic anhydride = 14 (molar ratio) corresponds, "the sum of the corresponding acids and acid components in the acid anhydride" H ₂ O / = 7 (molar ratio)) met Was. Example 6

In a 50-ml round-bottomed flask dried with a dryer at 70 ° C under an argon atmosphere, cyclododecanone oxime 2.5 5353 in which the water content was reduced to 0.128 wt ° / ₀ by vacuum drying. g (1 2.85 mmo 1) and 10.0 g of acetoethryl manufactured by Junsei Kagaku (water content 0 ppm (below the detection limit)) were charged. Under argon atmosphere, 77 in the flask. After heating to C, p-toluenesulfonic anhydride 0.0560 g (0.172 mmo 1) dissolved in 1.15 g of acetonitrile (water content: 0 ppm (below detection limit)) previously dried with Molecular Sieves 3 A, and the mixture is stirred with Beckmann rearrangement reaction. Was done.

The reaction solution temperature gradually increased from 2 minutes later, and reached 80 ° C after 12 minutes. After 35 minutes, the temperature reached 78 ° C, and the temperature was maintained until 1 hour and 7 minutes. The reaction solution was cooled, white crystals were collected by filtration under reduced pressure, and the white crystals were washed with cold acetonitrile. Each of the obtained white crystals and the mixture of the filtrate and the washing solution was analyzed by gas chromatography.

As a result, the white crystal contained 12.2 mmol of ω-laurinlatatam and 5 mmol of unreacted cyclododecanone oxime, and 1.04 mmol of ω-laurinlatatam in the solution. It was found that the reaction contained 0.01 mmo 1 of cyclododecanone oxime and 0.04 mmo 1 of cyclododecanone. The conversion of dodecanone oxime at the mouth was 99.5%, the selectivity of ω-laurinlactam was 99.7%, and the selectivity of dodecanone at the mouth was 0.3%. ,

(The TON value of ω-laurin ratatum was 77.)-In addition, acetoamide formed when the solvent aceto-tolyl reacted with water was not detected. (The detection limit is 0.00 lmo 1% for the solvent and 0.02mo 1% for the produced ratatum).

Before the start of the reaction, the molar ratio of the total amount of water contained in the dodecanonone oxime and acetonitrile to ρ-toluenesulfonic anhydride was 1.1.

table 1

氺 r>-Based on acid anhydride, reaction time 0.5 hours ** Reaction time 3 hours

*** Reaction time 1 hour 5 minutes As shown in Table 1, Oxime obtained by the usual method was used in Comparative Examples 1 and 2 where the reaction was performed in a solvent without special water removal operation. In Examples 1 to 6 in which the amount of water in the oxime was reduced and the reaction was carried out in a dried solvent, it is clear that the reaction results are superior. Reference example 2

A cyclododecanone oxime 20.21 g (0.102 mol), synthesized by the method of Reference Example 1 and reduced in water content to 0.249 wt% by drying under reduced pressure, was Dissolved in 1 L ethanol in the bottom flask. While maintaining the temperature in the round bottom flask at around 26 ° C, a solution of concentrated hydrochloric acid (36 wt%) mixed with 16.7 ml (0.2 mol as hydrochloric acid) and ethanol 5 Om1 (3 mol 1 ZL hydrochloric acid / ethanol aqueous solution) was added dropwise to the above solution. After stirring was further continued at 26 ° C. for 30 minutes, ethanol and water were distilled off under vacuum at room temperature, and further dried under reduced pressure at 400 ° C. at room temperature to obtain a white solid.

According to ¹ H-NMR and elemental analysis, this white solid was found to be cyclododecanone oxime hydrochloride of cyclododecanone oxime: HC1 = 1: 1 (molar ratio). Was. The water content was measured by the Karl Fischer method and found to contain 176 ppm of water. Example 7

In an argon atmosphere, in a 50-ml round-bottomed flask dried with a dryer at 70 ° C, 3.001 g (12.88399 mmo1) of the above-mentioned dodecanonone oxime hydrochloride was added. 10.13 g of acetonitrile manufactured by Junsei Chemical Co., Ltd. (water content: 0 ppm (lower than detection limit)) was charged. While stirring, the mixture was heated in an oil bath at 80 ° C. After the temperature in the flask was stabilized at 77 ° C., a solution prepared by dissolving 0.0556 g (0.1704 mmo 1) of p-toluenesulfonic anhydride in 1.23 g of acetoethrile was added. The temperature gradually increased to 81 ° C after 11 minutes. Thereafter, the temperature gradually decreased, and after 46 minutes, the temperature did not change from 77.2 ° C., and thus the temperature was cooled to room temperature.

A part of the reaction solution was taken out and neutralized with 28 wt% NH ₃ water. The generated crystals were separated by filtration and washed, and the components contained in each of the crystals and the filtrate were analyzed by gas chromatography.

As a result, it was found that the conversion of cyclododecanone oxime hydrochloride was 100% ·, the selectivity of ω-laurin lactam was 99.9%, and the selectivity of cyclododecanone was 0.1%. The TON based on ρ-toluenesulfonic anhydride was 74. The amount of acetamide produced by the reaction of acetonitrile with water was 0.19 mmo1, 0.07 mol 1% for the solvent, and 1.5 mol 1% for ratatam.

Before the start of the reaction, the molar ratio of the total amount of water contained in dodecanonone oxime hydrochloride and acetate in the mouth to J) monotoluenesulfonic anhydride was 0.2. Reference example 3

2.0023 g (8.5 65 mmol) of the above cyclododecanone oxime hydrochloride was placed in a 50 ml round bottom flask dried in a dryer at 70 ° C under an atmosphere of argon. 8. 8.06 g (water content: 0 ppm (below detection limit)) of acetoethryl manufactured by Junsei Chemical Co., Ltd. was charged. The mixture was heated in an 80 ° C oil bath with stirring under an argon atmosphere. The temperature in the flask gradually increased to 79.5 ° C after 30 minutes. Then, the temperature gradually decreased, and after 40 minutes had passed, the temperature became constant. After 45 minutes, the flask was removed from the oil bath, heating was stopped, and the flask was cooled to room temperature. It was a homogeneous solution when cooled to room temperature.

A part of the reaction solution was taken out and neutralized with 28 wt ° / oNH ₃ water. The generated crystals were separated by filtration and washed, and the components contained in each of the crystals and the filtrate were analyzed by gas chromatography. As a result, it was found that the conversion of cyclododecanone oxime hydrochloride was 100%, the selectivity of ω-laurin ratatam was 99.6%, and the selectivity of cyclododecanone was 0.4%. The amount of acetamide produced by the reaction with water was 0.24 mmο1, 0.12 mol% for the solvent, and 2.7 mol% for the lactam.

Before the start of the reaction, the molar ratio of the total amount of water contained in the dodecanonone oxime hydrochloride oxacetonitrile to the oxime hydrochloride was 0.002. Reference example 4

The same method as in Reference Example 3 was used, except that the dodecanonone oxime hydrochloride having a water content of 5.4% (dodecanonone oxime: HC 1 = 1: 1 (molar ratio)) was used. The temperature in the flask reached 77 ° C. in 12 minutes after the start of heating, but did not change from 77 ° C. After 42 minutes, the heating was stopped. At the end of the reaction, crystals had already precipitated, so after cooling to room temperature, the solid and the filtrate were separated, neutralized, and analyzed by gas chromatography.

As a result, it was found that the conversion of cyclododecanone oxime hydrochloride was 20.2%, the selectivity of ω-laurinlatatam was 37.3%, and the selectivity of cyclododecanone was 62.7%. . The amount of acetoamide generated by the reaction of acetonitrile with water was 0.28 mm ο1, which was 0.15 mol% based on the solvent. It was 47.7mo 1% based on the formed lactam.

Before the start of the reaction, the molar ratio of the total amount of water contained in dodecanonone oxime hydrochloride and acetonitrile to oxime hydrochloride was 0.7. Example 8

Under an argon atmosphere, cyclododecanone oxime whose water content was reduced to 0.07 wt% by reduced pressure drying in a 5 Oml round-bottom flask dried with a dryer at 70 ° C 10.0290 g ( 50.82 mmo1) and 40.1 g of toluene (water content Op pm (below the detection limit)) previously dried with molecular sieve 3 A were charged. 95. After heating to C, the dodecanonone oxime was dissolved, and 0.222 g (0.680 Ommo 1) of ρ-toluenesulphonic anhydride and 4.2 g of the above tonolenene were mixed (most of them). p-Toluenesulfonic anhydride was not dissolved in toluene), and the mixture was heated to 95 ° C and Beckmann rearrangement reaction was performed.

Even under the reaction conditions, most of the P-toluenesulfonic anhydride was not dissolved in the solvent but was dispersed in the solvent. After 6 minutes from the addition of p-toluenesulfonic anhydride, a mild exotherm was observed. The temperature was maintained at 97 ° C from 16 minutes to 5.5 minutes, and then decreased to 96 ° C.

The reaction solution was sampled as a hot solution, and analyzed by iH-NMil. As a result, the TON after 3 hours and 45 minutes was 41, and the TON after 6 hours was 39.

Before the reaction, the molar ratio of the water contained in the charged oxime and the solvent to p-toluenesulfonic anhydride was 0.6.

The reaction solution was cooled to room temperature and stored tightly. The stored reaction solution was equivalent to 99.3% of the charged reaction solution, and 1H-NMR analysis showed that unreacted dodecanononoxime was 23.9 mm o 1 and ω-laurin ratatam was 26.6 mm. o 1, p- Contains 1.4 mmo 1 of toluenesulfonic acid. After storage at room temperature for 2 weeks, the reaction solution was filtered under reduced pressure to separate the crystals and the filtrate, and the crystals were washed with a small amount of toluene cooled to 0 ° C, and the washed solution was combined with the filtrate. The crystals weighed 6.65 g and the filtrate weighed 50.lg. The filtrate was kept in a refrigerator at 0 ° C. for 2 days. Analysis The resulting crystals were similarly filtered under reduced pressure to separate from the filtrate. 1.555 g of crystals and 46.31 g of filtrate were obtained.

When these crystals and the filtrate were analyzed, it was found that in the obtained crystals, ω-laurinratham was 21.8 mmo1, unreacted cyclododecanone oxime was 17.3 mmo1, p-tonolenesulfonic acid 0.08mnio 1 was detected.

Further, in the filtrate, .omega. Raurinratatamu is 3. 9mmo 1, Shikurodo Dekanonokishimu unreacted 4. 3Mmo is 1 _s p-toluenesulfonic acid was found to contain 1. 4mmo l.

At this stage, with respect to the crystallization charge, 82 mol 1% of ω-laurinlatatam was recovered in the crystal, and 72 mol 1% of unreacted cyclododecanone oxime was recovered. Further, the filtrate was concentrated until the amount of toluene became 10 g, and crystallization was performed again at 0 ° C. In the obtained crystals, ω.-laurin ratatam 1.5 mmo 1 Dodecanone oxime contained 2.2 mmo 1 and monotoluenesulfonic acid at 0.01 mmo 1. As a result of these series of crystallization operations, ω-laurinlactam was recovered in an amount of 88 mol% and unreacted neck-mouth dodecanone oxime was recovered in an amount of 82 mol%. -Toluenesulfonic acid was mixed in the crystals in an amount of 6.4 mol% of the crystallization charge. -Example 9

Cyclododecanone was prepared in the same manner as in Example 2 except that instead of toluene, dehydrated water of 0.0004 1: ° / ₀ ; ^, N-dimethylformamide (DMF) was used. A Beckmann rearrangement reaction of Kissim was performed. P-toluenesulfonic anhydride was dissolved in DMF and added to a DMF solution of cyclododecanone oxime. Immediately after the addition, the temperature of the reaction solution rose to 120 ° C, then gradually decreased, and after 40 minutes had passed, the temperature reached 96 ° C—a constant temperature.

The reaction solution was sampled as a hot solution and analyzed by iH-NMR. As a result, the yield of ω-laurin ratatam after 30 minutes was 80.2%, and the TON value was 59. Sampling was performed at 45 minutes for 2 hours and 50 minutes for 3 hours. 2003/009749 There was not.

Before the reaction, the molar ratio of the water contained in the charged oxime and the solvent to the water of P-toluenesulfonic anhydride was 0.6.

The reaction solution obtained after the completion of the reaction was in an amount corresponding to 98.3 wt% of the preparation. The reaction solution according to the analysis results of the H-NMIL, cyclododecanone O carboxymethyl arm of 1 1. 3mmo l unreacted an ω- Raurinratatamu 38. The 8 mm o 1 _s p-Tosuree Nsuruhon acid 1. It contained 4 mmol. The reaction solution was cooled to room temperature to precipitate crystals. After filtration under reduced pressure to separate the crystals and the filtrate, the crystals were washed with a small amount of DMF cooled to 0 ° C. At this time, the weight of the obtained crystal was 1.59 g, and the filtrate was 50.66 g. The filtrate was kept in a refrigerator at 0 ° C. for 2 days. The precipitated crystals were similarly filtered under reduced pressure to separate from the filtrate. The crystals at this time were 3.lg and the filtrate was 45.05 g.

When these crystals and the filtrate were analyzed, it was found that ω-laurin ratamone contained 17.3 mm ο .1 and unreacted cyclododecanone oxime contained 4.2 mm o 1, _p _ It was found that ensnolefonic acid contained 0.02 mmo1. In addition, it was found that the filtrate contained 9.6 mmol of ω-laurin ratatam, 15.5 lmmol of unreacted cyclododecanone oxime, and 1.4 mmol of p-toluenesulfonic acid.

At this stage, about 45 mol 1% of ω-laurinlatatam was recovered in the crystal, and about 37 mol 1% of unreacted dodecanonone oxime was recovered in the crystal.

Further, the filtrate was concentrated until the DMF was reduced to 5.7 g, and 4.0 g of toluene was added. Then, crystallization was performed again at 0 ° C., and ω-laurin lactam 6. 7 mm o 1 _N unreacted cyclododecanone oxime was detected at 4.2 mm o 1, and p-toluenesulfonic acid was not detected. As a result of this series of crystallization operations, ω-laurinlactam was recovered in an amount of 62 mol 1%, and unreacted dodecanonone oxime was recovered in an amount of 74 mol 1%. The mixing of ρ-toluenesulphonic acid into the crystal was 1.5 mo 1 of the crystallization preparation. /. Met. Example 10

In a 5 Oml round-bottom flask (reactor 1) dried in a dryer at 70 ° C under an argon atmosphere, cyclododecanone oxime 5.0486 g whose water content was reduced to ◦ 07 wt% by drying under reduced pressure (25.59 mmo 1) and 42.7 g (water content: 0.4 wt%, 0.4 wt%) of DMF previously dried with Molecular Sheep 3A. After the cyclododecanone oxime was dissolved by heating to 95 ° C under an argon atmosphere, 0.227 g (0.6955 mmo1) of P-toluenesnorenoic anhydride was added to 2.6 g of the above DMF. The dissolved solution was added, and the mixture was heated and stirred for 30 minutes to perform a Beckmann rearrangement reaction. Immediately after the addition of p-toluenesulfonic anhydride, the reaction temperature rose to 122 ° C, and then gradually decreased.After 12 minutes, it dropped to 96.5 ° C and remained there for 30 minutes. The temperature was maintained.

The reaction solution was placed in an ice bath to precipitate crystals, and then most of the solution components were taken out using a syringe dried in a drier at 70 ° C. In a 5 Oml round bottom flask (Reactor 2) dried in a separate 70 ° C dryer under an argon atmosphere, the cyclododeca water content was reduced to 0.07 wt% by vacuum drying. 5.0549 g (25.62 mmo 1) of nonoxime was charged, and the solution component collected from the reactor 1 by a syringe was charged to the reactor 2. At this time, the amount of the solution transferred from the reactor 1 to the reactor 2 was 33.35 g, and the amount of the solution remaining in the syringe was 2.20 g.

The reactor 2 was heated and stirred at 95 ° C. under an argon atmosphere to carry out a Beckmann rearrangement reaction. The components of each reactor were analyzed by 1H-NMR.As a result, ω-laurin ratatam produced in reactor 1 was 25.59 mmol (ΤΟΝ = 39), and ω-laurin ratatam newly produced in reactor 2 was 2. It was 4 ol (TON = 5), and ω = Laulinlactam of Totanore was ΤΟΝ = 44.

Further, the amount of ω-laurin lactam contained in the crystals remaining in the reactor 1 was 11.6 mmo1, and 45 mol% of the generated ω-laurin lactam was recovered in the crystals. Also, p-toluenesulfonic acid, which is a catalyst component, is contained in the same crystal at a concentration of 0. 2 lmmol (15mo 1% of the charged component) was contained in the crystals, and most of the catalyst components were transferred to the reactor 2, and it was found that the Beckmann rearrangement reaction also proceeded in the reactor 2.

Before the reaction, the molar ratio of the water contained in the charged oxime and the solvent to p-toluenesulfonic anhydride was 0.6. Example 11

(Beckmann reaction process)

In a 3 O Oml four-necked flask previously dried in a dryer at 70 ° C, cyclododecanone oxime with a moisture content of 0.249 wt% under dry nitrogen was 43.99 g (0.2229 mol 1) In addition, 178.55 g of acetonitrile (moisture content: 0 ppm (below detection limit)), which had been dried with molecular sieves 3 A previously heat-treated at 300 ° C., was charged. A cooling tube and a thermometer were connected to the four-necked flask under an argon stream, and the temperature inside the reactor was raised to 77 ° C while stirring.

In a 1 Om 1 sample bottle previously dried with a dryer at 70 ° C, weigh p-toluenesulfonic anhydride 1.01 2.2 g (3.10 lmmo 1), and heat-treat the molecular weight at 300 ° C in advance. After dissolving with 1.94 g of acetonitrile dried with 1 A bus 3A, it was added to the above reactor.

After 4 minutes, the temperature inside the reactor rose to 79 ° C, 9 minutes later, reached 84 ° C, kept at 84 ° C for 25 minutes, gradually decreased, and after 46 minutes 77. It was 5 ° C. After 1 hour, the reaction solution was sampled as a hot solution, and analyzed by NMR. As a result, it was found that ω-laurinlactam 0.219mo1 and cyclododecanone oxime 4.3mmo1 were detected. The yield of ω-laurin ratatam was 98% and TON 值 was 70.

After 1 hour and 40 minutes, heating was stopped and the reactor was cooled to room temperature.

The amount of water contained in the oxime and solvent used before the reaction was p-

The molar ratio of water to sulfonic anhydride was 2.0. (ω-crystallization process of laurin lactam)

After cooling the reaction solution to room temperature, it was cooled on ice to precipitate white crystals. The crystals were separated by filtration under reduced pressure and washed with ice-cooled acetonitrile. 35.65 g of the crystals, the filtrate and the washings were combined to give 30.375 g. When the crystals were analyzed by ¹ H-NMR, ω-laurin latatum was detected and ρ-toluenesulfonic acid was not detected.

(Neutralization process of catalyst component after crystallization)

At room temperature, the filtrate and the washings were neutralized with 4.8 g of 4.7 wt% aqueous ammonia. Crystals precipitated, but were evaporated to dryness. Then, water was added to the solid, and the solid was filtered and washed to obtain 7.36 g of the solid and 11.12.13 g of the filtrate.

Ifi— NMR analysis revealed that the solids contained 35.8 mm o 1 of ω-laurin ratatam, 3.5 mm o 1 of dodecanonone oxime, and 0.12 mm o 1 of ρ-tonolene sulfonic acid structure. The components were found to be contained. The filtrate was found to contain a component having a p-toluenesulfonic acid structure of 5.9 mm o 1.

Since the component of this p-toluenesulfonic acid structure was neutralized with NH 3 water, it was ammonium p-toluenesulfonic acid, but the recovery was 95.2 mol% based on the charged reaction. The recovered ω-laurin ratatum is 16 mo 1% of the generated ratatum, and the ω-laurin ratatum recovered as a solid component is 99.6 mol% together with the crystallized component.

From this filtrate, water was evaporated to dryness and dried at 400 Pa at room temperature to obtain 1.23 g of a solid component mainly composed of ammonium p-toluenesulfonate.

The above reaction and post-treatment operations were repeated twice to obtain 2.46 g of a solid component mainly composed of ammonium p-toluenesulfonic acid.

Since the solid component contained a small amount of ω-laurin ratatam, dissolve the solid component in 11.9 g of water, filter the solid with a 0.5 μm membrane filter, and then remove the water. After evaporation to dryness, 2.3 g of a solid component mainly composed of ammonium p-toluenesulfonate was obtained.

According to H-NMR analysis, the solid component obtained was p-toluenesulfonic acid 3009749 Nmo - besides © beam, _omega - Lau cyclododecanone O key shim lactam and unreacted are contained trace amounts, cyclododecanone O oxime of ω- laurolactam and unreacted against p_-toluenesulfonic acid Anmoniumu Was 0.08. Also, when converted on a weight basis, the purity of ammonium ρ-toluenesulfonic acid was 91.7 wt%.

(Regeneration process to p-toluenesulfonic acid)

2.29 g of the obtained crystal mainly composed of ammonium p-toluenesulfonate (equivalent to 1.1 lmmol of ammonium p-toluenesulfonate), 8 Oml of toluene, 1.75 g of 95% sulfuric acid ( 1 7. Ommo 1) was charged to the reactor. The temperature of the oil bath was heated to 130 ° C with stirring under atmospheric pressure to condense the generated steam. After the condensation, water was removed by a phase separator and only toluene was returned to the reactor. This reflux treatment was performed for 60 minutes. After the treatment, the reactor was allowed to stand, and the reactor was separated into two layers. This toluene phase was refluxed, and water was obtained with the above phase separator. The toluene solution of monotoluenesulfonic acid was removed by an evaporator to remove toluene, and p-toluenesulfonic acid crystals were obtained. At this time: — The yield of toluene sulfonic acid was 93 mol% based on the amount of p-toluenesulfonic acid used in the regeneration process of p-toluenesulfonic acid. Was 90 wt%. The total molar ratio of ω-laurinlactam and unreacted dodecanonone oxime to p-toluenesulfonic acid was 0.03.

(ρ—Regeneration process of tonorenensnorephonic anhydride)

Under a nitrogen atmosphere, 1.94 g of a solid containing 90 wt% of Ρ-toluenesulfonic acid and 1.38 g (13.5 1 mmo1) g of acetic anhydride obtained by the above operation were charged into a flask. The mixture was stirred for 30 minutes to dissolve the solid components. The oil bath temperature was raised to 60 ° C, and the mixture was further stirred for 20 minutes. 80 minutes after the temperature reached 60 ° C, the pressure was reduced to 400 Pa, and stirring was continued for 30 minutes. Further, the oil bath temperature was raised to 95 ° C while maintaining the reduced pressure condition, and the temperature was maintained for 1.5 hours with stirring. After 5 minutes had passed, it was almost solidified and could not be stirred. Next, the reactor was taken out of the oil bath and cooled. -After returning to atmospheric pressure, 0.991 g of acetic anhydride (0.972 mmo 1) was added to the reactor,

Similarly, the mixture was stirred at room temperature for 20 minutes and subsequently at 60 ° C for 20 minutes. Subsequently, the pressure was reduced to 400 Pa with a vacuum pump, and the mixture was stirred at 60 ° C. for 30 minutes. Subsequently, the mixture was stirred at 95 ° C for 1 hour and 30 minutes while maintaining the reduced pressure condition. The flask was cooled and returned to atmospheric pressure under a stream of dry nitrogen. 1.8992 g of crude p_toluenesulfonic anhydride was obtained from the flask.

(Purification process of p-toluenesulfonic anhydride)

1.67 g of acetic anhydride was added to 1.892 g of the obtained crude P-toluenesulfonic anhydride, followed by stirring at room temperature for 20 minutes. Some components dissolved in acetic anhydride and others did not. This mixture was filtered under a sufficiently dry atmosphere. The obtained solid was washed by sprinkling a total of 2.91 g of acetic anhydride. The obtained cake was dried at room temperature under a reduced pressure of 400 Pa. The obtained crystals weighed 1.2026 g (total _p- 3.6846 mm o 1, assuming tonnoreensnorephonic anhydride), and were analyzed by ¹ H-NMR. —It was found to be toluenesulfonic anhydride. The yield of the obtained p-toluenesulfonic anhydride was 73 mol% based on the P-small ruenesulfonic acid used in the regeneration reaction of the acid anhydride.

(Beckmann rearrangement reaction step using regenerated p-toluenesulfonic anhydride) Same as above except that the above-mentioned P-tonolene snolefonic anhydride was performed on a scale of 18 mo 1 ° / ₀ of the above Beckmann rearrangement reaction. Was subjected to a Beckmann rearrangement reaction. As a result, TON = 72 was obtained.

Played! ) Similar reaction results were obtained using monotoluenesulfonic anhydride. Although the present invention has been described in detail and with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention.

This application is a Japanese patent application filed on July 31, 2002 (Japanese Patent Application No. 2002-224011). 3 This is based on a Japanese patent application filed on July 31, 2007 (Japanese Patent Application No. 2002-224012), the contents of which are incorporated herein by reference. Industrial applicability>

According to the method of the present invention, an amide compound can be produced at a high yield from an oxime compound under mild reaction conditions, and the amide compound and the catalyst component can be easily separated to regenerate the catalyst component, which is industrially advantageous. It is a way.

Claims

The scope of the claims

1. In a method for producing an amide compound by subjecting an oxime compound having 8 or more carbon atoms to a Beckmann rearrangement reaction in an organic solvent in the presence of a catalyst component containing an acid anhydride, the oxime compound is included in the oxime compound and the solvent. A process for producing an amide compound, wherein the rearrangement reaction is carried out by setting the total molar ratio of water to 15 or less with respect to the added acid anhydride.

2. The method according to claim 1, wherein the catalyst component containing an acid anhydride is a strong acid anhydride.

3. The method according to claim 1, wherein the catalyst component containing an acid anhydride is a carboxylic acid anhydride and a strong acid and / or a strong acid anhydride.

4. The method according to any one of claims 1 to 3, wherein the catalyst component and the amide compound are directly separated from the reaction solution after the rearrangement reaction.

5. The method according to claim 4, wherein the catalyst component and the amide compound are separated in a state where the catalyst has not been deactivated.

6. The method according to claim 4 or 5, wherein the separation is a crystallization separation.

7. The method according to claim 6, wherein, after the crystallization separation, the separated catalyst component is recycled to a rearrangement reaction.

8. The catalyst component separated after the rearrangement reaction is dehydrated and condensed into an acid anhydride to be regenerated, and the regenerated acid anhydride is used again for the rearrangement reaction. A method according to any of paragraphs 7.

9. The method according to any one of claims 1 to 8, wherein the oxime compound is a cyclic oxime compound.

10. The method according to any one of claims 1 to 9, wherein the oxime compound is dodecanonone oxime, and the amide compound is ω-laurinlatatam.

11. A method for producing an amide compound by subjecting an oxime compound to an amide compound in the presence of a catalyst component containing an acid anhydride in an organic solvent, wherein the catalyst component and the amide compound are directly reacted from the reaction solution after the rearrangement reaction. And a method for producing an amide compound.