JP2003081941A - Method for producing n-hydroxyl cyclic imide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a high-purity N-hydroxyl cyclic imide in high yield and good operability from a cyclic acid anhydride and hydroxylamine or a salt thereof as raw materials. SOLUTION: This N-hydroxyl cyclic imide is obtained by a reaction between the cyclic acid anhydride of general formula (1) (where, R<1> and R<2> are each H, an alkyl, aryl, halogen atom, alkoxy, alkoxycarbonyl, acyl, OH or COOH, or joined each other to form an aromatic or nonaromatic ring together with the carbon atoms to which R<1> and R<2> are bound; and a part where a real line and a dotted line are in parallel to each other denotes a single or double bond) and hydroxylamine or a salt thereof while adding these reactants to an aqueous solvent.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing an N-hydroxy cyclic imide from a cyclic acid anhydride and hydroxylamine or a salt thereof as raw materials. The N-hydroxy cyclic imide is used as a reagent for peptide synthesis, an oxidation catalyst and the like.

[0002]

2. Description of the Related Art Conventionally, a method of reacting a corresponding cyclic acid anhydride with hydroxylamine or a salt thereof is known as one of the methods for producing an N-hydroxy cyclic imide. For example, Indian Journal of Chemistry, Vol. 33B, pp. 1175-1177 (1994), phthalic anhydride and hydroxylamine hydrochloride were heated in pyridine and then acetic anhydride was added. By further heating, N-
It is described to obtain hydroxyphthalimide.
In addition, WO 95/25090 pamphlet describes that N-hydroxyphthalimide is obtained by pouring an aqueous solution of hydroxylamine sulfate and an aqueous solution of sodium hydroxide together into phthalic anhydride in water, followed by heating. Has been done. In addition, Japanese Patent Laid-Open No. 2001-12285
No. 9 discloses that various cyclic acid anhydrides and hydroxylamine phosphate are mixed, water is added and the mixture is heated.
It is described to obtain various N-hydroxy cyclic imides.

[0003]

However, according to the conventional method, the purity and yield of the obtained N-hydroxy cyclic imide are not sufficient, and the operability during the reaction and the post-treatment is not sufficient. , Was not always satisfactory. Therefore, an object of the present invention is to produce a high-purity N-hydroxy cyclic imide with a good yield and good operability.

[0004]

Means for Solving the Problems As a result of intensive studies, the present inventors have used an aqueous solvent as a reaction solvent when reacting a cyclic acid anhydride with hydroxylamine or a salt thereof,
Moreover, they have found that the above object can be achieved by pouring the above raw materials together, and have completed the present invention. That is, the present invention relates to a method for producing an N-hydroxy cyclic imide by reacting a cyclic acid anhydride with hydroxylamine or a salt thereof in an aqueous solvent.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below.
The cyclic acid anhydride used in the present invention is preferably a 5-membered cyclic one or a 6-membered cyclic anhydride, among which the following general formula (1)

[Chemical 2] (In the formula, R ¹ and R ² are each independently a hydrogen atom,
Represents an alkyl group, an aryl group, a halogen atom, an alkoxy group, an alkoxycarbonyl group, an acyl group, a hydroxyl group or a carboxyl group, or R ¹ and R ² together form an aromatic group together with the carbon atom to which they are attached. Alternatively, a portion forming a non-aromatic ring and having a dotted line and a solid line in parallel represents a single bond or a double bond. A 5-membered cyclic compound such as the compound shown in (4) is preferable.

In the general formula (1), when R ¹ or R ² is an alkyl group, an alkoxy group or an alkoxycarbonyl group, the alkyl group, the alkyl group in the alkoxy group and the alkyl group in the alkoxycarbonyl group include For example, methyl group, ethyl group, n-
Linear or branched such as propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group Alkyl groups; cycloalkyl groups such as cyclopentyl group, cyclohexyl group and cyclooctyl group; alkylcycloalkyl groups, cycloalkylalkyl groups and the like, and the number of carbon atoms of these alkyl groups is usually 1 to 10, preferably 1 -6, more preferably 1-4.

[0007] In the general formula (1), when R ¹ or R ² is an aryl group, as the aryl group include a phenyl group, an alkyl-substituted phenyl group, a naphthyl group, etc. pyridyl group can be mentioned, R ¹ or When R ² is a halogen atom, examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, preferably a chlorine atom and a bromine atom, and more preferably a chlorine atom.

In the general formula (1), when R ¹ or R ² is an acyl group, examples of the acyl group include formyl group, acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, isovaleryl group. Group, pivaloyl group, benzoyl group and the like, and the carbon number of these acyl groups is usually 1 to 10, preferably 1 to 6, and more preferably 1 to 4.

Further, in the general formula (1), when R ¹ and R ² are bonded to each other to form an aromatic or non-aromatic ring, the number of ring members is usually 5 to 12, preferably Is 6 ~
And the type of ring is, for example, a benzene ring,
Examples thereof include an aromatic hydrocarbon ring such as a naphthalene ring; a cycloalkane ring such as a cyclohexane ring; and a cycloalkene ring such as a cyclohexene ring, and an aromatic hydrocarbon ring is preferable. The ring may have a substituent and may be a heterocycle.

Examples of the compound represented by the general formula (1) include succinic anhydride, maleic anhydride, tetrahydrophthalic anhydride, hexahydrophthalic anhydride, 1,2,3,4.
-Cyclohexanetetracarboxylic acid 1,2-anhydride, phthalic anhydride, tetrabromophthalic anhydride, tetrachlorophthalic anhydride, nitrophthalic anhydride, trimellitic anhydride, methylcyclohexene tricarboxylic anhydride, and the like. Succinic acid and phthalic anhydride are preferred. In addition, examples of cyclic acid anhydrides other than the compound represented by the general formula (1) include pyromellitic dianhydride, mellitic anhydride, and the like, and these can be used as the starting cyclic acid anhydride.

In the present invention, the reaction is carried out by pouring the above cyclic acid anhydride together with hydroxylamine or a salt thereof into an aqueous solvent. Examples of the hydroxylamine salt include hydrochlorides, sulfates, nitrates, phosphates and the like, with preference given to hydrochlorides and sulfates. The usage-amount of hydroxylamine or its salt is 0.1-10 mol normally with respect to 1 mol of cyclic acid anhydride, Preferably it is 0.3.
-5 mol, more preferably 0.5-2 mol. Further, as the hydroxylamine or a salt thereof, it is preferable to use an aqueous solution from the viewpoint of operability.

As the above-mentioned aqueous solvent, water alone or water 5 is used.
A mixed solvent of 0% by weight or more and an organic solvent of 50% by weight or less is used. The organic solvent is preferably a water-miscible one, for example, alcohols such as methanol, ethanol and isopropanol; ethers such as dioxane; aprotic polar solvents such as acetonitrile and N, N-dimethylformamide. Etc.,
Two or more of them may be used if necessary.
The amount of the aqueous solvent used is usually 100 to 10,000 parts by weight, preferably 100 parts by weight, based on 100 parts by weight of the cyclic acid anhydride.
~ 3000 parts by weight, more preferably 200-2000
Parts by weight.

During the above-mentioned co-injection, the pH of the reaction solution is preferably adjusted to 4 to 6, and more preferably 4.5 to 5.5, from the viewpoint of yield and quality. This pH adjustment is usually carried out by adding an acid when hydroxylamine is used as the above hydroxylamine or a salt thereof, and by adding a base when a hydroxylamine salt is used. . As an acid,
Examples thereof include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and the like, and examples of the base include metal hydroxides such as sodium hydroxide, potassium hydroxide, magnesium hydroxide and calcium hydroxide; sodium carbonate, carbonic acid. Examples thereof include metal carbonates such as potassium and magnesium carbonate; metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; metal acetates such as sodium acetate and potassium acetate. Among the bases, metal hydroxides and metal acetates are preferable, and sodium hydroxide and sodium acetate are more preferable.

The temperature during the co-injection is usually 20 to 70 ° C., preferably 40 to 60 ° C., and the time required for the co-injection is usually 1 to 40 hours, preferably 2 to 10 hours.

After the above-mentioned co-injection, the pH of the reaction solution is preferably adjusted to 2 to 4, more preferably 2.5 to 3.5, and then maintained. In some cases, intermediates such as amidocarboxylic acids remaining in the reaction mixture can be converted to N-hydroxy cyclic imides. The pH adjustment during this holding can be performed by adding the same acid or base as described above.

The temperature during the above holding is usually 20 to 70.
C., preferably 40 to 60.degree. C., and the holding time is usually 1 to 40 hours, preferably 2 to 10 hours.

The method for taking out the N-hydroxy cyclic imide from the obtained reaction mixture can be appropriately selected. For example, when N-hydroxy cyclic imide is precipitated in the reaction mixture, it can be optionally used. After concentrating and cooling with N, the N-hydroxy cyclic imide may be separated by filtration or decantation, or N-hydroxy cyclic imide may be separated in the reaction mixture.
When the -hydroxy cyclic imide is dissolved, the reaction mixture may be concentrated or cooled to precipitate the N-hydroxy cyclic imide, which may be separated by filtration or decantation. Alternatively, the N-hydroxy cyclic imide may be extracted from the reaction mixture using an organic solvent.

According to the production method of the present invention described above, a corresponding N-hydroxy cyclic imide can be produced from a cyclic acid anhydride and hydroxylamine or a salt thereof in good yield and purity with good operability. For example, when the compound of the general formula (1) is used as the cyclic acid anhydride, the following general formula (2)

[Chemical 3] (In the formula, R ¹ , R ² and the portion where the dotted line and the solid line are parallel have the same meaning as described above.) The N-hydroxy cyclic imide can be produced.

[0019]

EXAMPLES Examples of the present invention will be shown below, but the present invention is not limited thereto.

Example 1 92.3 g of water was added to a four-necked flask equipped with a reflux condenser, a powder charging device, a thermometer, a pH meter and a dropping funnel, and stirred therein at 50 ° C. under stirring. Phthalic anhydride 3
2.6 g (0.220 mol) was added from the powder feeding device over 1 hour, and hydroxylamine sulfate [(N
H ₂ OH) ₂ · H ₂ SO ₄ ] 27.1 g (0.165 mol)
Was dissolved in 198 g of water and added through the dropping funnel over 1 hour. During the co-injection of the phthalic anhydride and the hydroxylamine sulfate aqueous solution, the pH of the reaction solution was adjusted to 5.0 by adding a 25 wt% sodium hydroxide aqueous solution. The required 25 wt% sodium hydroxide aqueous solution is 7
It was 1.3 g (0.445 mol). 5 after completion of co-injection
The temperature of the reaction solution was kept at 0 ° C. for 5 hours, and the pH of the reaction solution was adjusted to 3.0 by adding 25% by weight sulfuric acid during the holding. The required 25% by weight sulfuric acid was 46.4 g (0.118 mol). The obtained reaction mixture (slurry) was added to 3
After cooling to 0 ° C., it was filtered. Next, the filter residue was washed with water and dried to obtain 26.5 g of N-hydroxyphthalimide (purity 96.6%, yield 71.2%). The yield of N-hydroxyphthalimide contained in the filtrate and the washing liquid was 2.8%.

Example 2 In Example 1, a total of 57.7 g (0.360 g) was obtained during the simultaneous injection of phthalic anhydride and hydroxylamine sulfate aqueous solution.
The pH of the reaction solution is adjusted to 4.0 by adding 25% by weight of a 25% by weight sodium hydroxide aqueous solution, and a total of 31.1 g (0.079 mol) of 25
The pH of the reaction solution was adjusted to 3.0 by adding sulfuric acid in weight%.
The same operation as in Example 1 was performed except that the adjustment was made to 1. N
-Hydroxyphthalimide 25.4 g (purity 93.7
%, Yield 66.2%) was obtained. The yield of N-hydroxyphthalimide contained in the filtrate and the washing liquid was 2.6%.

Example 3 Example 1 was repeated except that the temperature between the co-injection of the phthalic anhydride and the aqueous solution of hydroxylamine sulfate and the temperature during the holding after the co-injection were 60 ° C. The same operation was performed. 22.8 g of N-hydroxyphthalimide (purity 99% or more, yield 63.4%) was obtained. The yield of N-hydroxyphthalimide contained in the filtrate and the washing liquid was 2.2%.

Comparative Example 1 198.4 g of water and hydroxylamine sulfate [(NH ₂ OH) ₂ · H ₂ SO ₄ ] were placed in a four-necked flask equipped with a reflux condenser, a powder charging device, a thermometer and a pH meter. Two
After adding 7.1 g (0.165 mol), pH was adjusted to 5.0 by adding 7.2 g (0.045 mol) of 25 wt% sodium hydroxide aqueous solution. While stirring, 5
32.6 g (0.220 mol) of phthalic anhydride at 0 ° C
Was added from the powder feeding device over 1 hour, and the pH of the reaction solution was adjusted to 5.0 by adding a 25 wt% sodium hydroxide aqueous solution. 25% by weight required additionally
The sodium hydroxide aqueous solution was 59.4 g (0.371 mol). Then, the mixture was held at 50 ° C. for 5 hours, and during this holding, 25 wt% sulfuric acid was added to adjust the pH of the reaction solution to 3.0. 25% by weight sulfuric acid required was 4
It was 8.4 g (0.123 mol). The obtained reaction mixture (slurry) was cooled to 30 ° C. and then filtered. Then, the filter residue is washed with water and then dried,
30.1 g of N-hydroxyphthalimide (purity 72.6
%, Yield 61.0%) was obtained. The yield of N-hydroxyphthalimide contained in the filtrate and the washing liquid was 1.6.
%Met.

[0024]

INDUSTRIAL APPLICABILITY According to the present invention, a cyclic acid anhydride and hydroxylamine or a salt thereof are used as raw materials to obtain N-purity of high purity.
The hydroxy cyclic imide can be produced in good yield and good operability.

Claims (5)

[Claims] 1. A process for producing an N-hydroxy cyclic imide, which comprises reacting a cyclic acid anhydride with hydroxylamine or a salt thereof in an aqueous solvent. 2. A cyclic acid anhydride is represented by the following general formula (1): (In the formula, R ¹ and R ² are each independently a hydrogen atom,
Represents an alkyl group, an aryl group, a halogen atom, an alkoxy group, an alkoxycarbonyl group, an acyl group, a hydroxyl group or a carboxyl group, or R ¹ and R ² together form an aromatic group together with the carbon atom to which they are attached. Alternatively, a portion forming a non-aromatic ring and having a dotted line and a solid line in parallel represents a single bond or a double bond. The manufacturing method of Claim 1 which is a compound shown by these. 3. The method according to claim 1, wherein the cyclic acid anhydride is succinic anhydride or phthalic anhydride. 4. The production method according to claim 1, wherein the pH of the reaction solution is adjusted to 4 to 6 while adding the cyclic acid anhydride and hydroxylamine or a salt thereof. 5. The production method according to claim 1, wherein the pH of the reaction solution is adjusted to 2 to 4 and then maintained after the cyclic acid anhydride and hydroxylamine or a salt thereof are added.