JPWO2014007144A1 - Method for producing alicyclic N-oxyl compound - Google Patents

Abstract

A method for producing an alicyclic N-oxyl compound by oxidizing an alicyclic secondary amine with an oxidizing agent, wherein the alicyclic secondary amine compound and sodium percarbonate are contained in a solid dispersed phase comprising hydrotalcite. The alicyclic secondary amine compound is oxidized in the solid dispersed phase by mixing an oxidant such as, and the oxidation reaction is difficult in the solid dispersed phase and is difficult to regenerate and reuse. The reaction can be carried out without using a catalyst, and a higher conversion rate and selectivity can be obtained, and the solid dispersed phase can be reused.

Description

  The present invention relates to a method for producing an alicyclic N-oxyl compound, which comprises oxidizing an alicyclic secondary amine compound in a solid dispersion phase.

  N-oxyl compounds such as 2,2,6,6-tetramethylpiperidine-N-oxyl (hereinafter referred to as “TEMPO”) are unsaturated polymer radical polymerization inhibitors, light stabilizers, and co-oxidation of oxidation reactions. It is an organic nitroxy radical compound used as an agent. In addition to TEMPO, various N-oxyl compounds have been developed in recent years and are expected as functional materials. This N-oxyl compound can be produced by oxidizing a secondary amine compound with hydrogen peroxide or the like, and various production methods are known.

  For example, Patent Document 1 discloses a method in which a secondary amine and hydrogen peroxide are reacted in the presence of a tungsten oxide catalyst. Patent Document 2 discloses a method of reacting a secondary amine and hydrogen peroxide in a non-reactive catalyst system. Further, Patent Document 3 discloses that 2-azaadamantane is oxidized with urea-hydrogen peroxide complex (UHP) in methanol and methylene chloride using sodium tungstate dihydrate as a catalyst. A method for producing N-oxyl is disclosed.

JP 2004-149513 A International Publication WO2011 / 125437 International Publication No. WO2009 / 066735

  However, these are a method using a solvent or a method using a large amount of hydrogen peroxide water, and both are methods in which an oxidation reaction is carried out in a liquid phase system mainly composed of a solvent, hydrogen peroxide water or the like. Therefore, after the reaction, a step of separating the product from the liquid phase is required. There is also a problem of treatment of water and solvent remaining after the reaction. Moreover, although the method described in the said patent document 1 and 3 is a method using a catalyst, the reproduction | regeneration and reuse of this catalyst are difficult, and the method of using no catalyst is desired. Furthermore, the conventional method has a problem that the N-hydroxyl compound is easily produced as a by-product and the conversion rate and selectivity of the N-oxyl compound are lowered.

  The present invention solves the above-described problems of the prior art, and is a method for producing an alicyclic N-oxyl compound by oxidizing an alicyclic secondary amine with an oxidizing agent, wherein the oxidation reaction It is an object of the present invention to provide a method that can be carried out without using a catalyst that is difficult to regenerate and reuse in a dispersed phase, and that can provide a higher conversion rate and selectivity.

  As a result of earnest research, the present inventor has used hydrotalcite as a solid dispersed phase, and in this solid dispersed phase, an alicyclic secondary amine is oxidized with an oxidizing agent, so that a catalyst is not used. The present inventors have found that an alicyclic N-oxyl compound can be obtained with high conversion and selectivity. That is, said subject is solved by the invention which consists of a structure shown below.

  The invention according to claim 1 is a mixture of an alicyclic secondary amine compound and an oxidizing agent in a solid dispersed phase comprising hydrotalcite, and the alicyclic secondary amine compound is mixed in the solid dispersed phase. It is the manufacturing method of the alicyclic N-oxyl compound characterized by oxidizing with.

  The production method of the present invention oxidizes an alicyclic secondary amine compound in a state where an alicyclic secondary amine compound and an oxidizing agent are dispersed in a solid dispersion phase, that is, a solid phase system or a state close to a solid phase system. It is characterized by doing. Here, the solid phase system refers to a system having fluidity that can be stirred but also having self-retaining properties, that is, a system having a shape that does not collapse due to its own weight. In addition, the state close to a solid phase system does not have a self-retaining property, but the weight of the liquid component (including the oxidant solvent) contained in the system is twice the weight of the solid dispersed phase. Say when: By performing the reaction in a solid phase system or a state close to a solid phase system, separation of the product after the reaction is facilitated, and the burden of processing the solvent after the reaction is reduced. This effect is that, even in a solid phase system or a state close to a solid phase system, the weight of the liquid component (including the oxidizing agent solvent) in the solid phase system or the system is 1 with respect to the weight of the solid dispersed phase. The weight is preferably less than the weight, and the product after the reaction is more easily separated, and the burden of the solvent treatment after the reaction is further reduced.

  Further, in this production method, no catalyst is used, so that a step of regenerating or reusing the catalyst is unnecessary. Therefore, the environmental load of this manufacturing method is low. Furthermore, according to this production method, an alicyclic N-oxyl compound can be obtained from an alicyclic secondary amine with high conversion and selectivity. That is, high conversion and selectivity can be achieved without using a catalyst (for example, the polyacid catalyst described in Patent Document 3).

  Various methods have already been proposed for performing a reaction for oxidizing an organic compound with an oxidizing agent in a solid phase system instead of a liquid phase system. For example, in Japanese Patent Application Laid-Open No. 2010-265332, a powdered polymer is mixed with a hydrogen peroxide solution, an oxidizing agent with urea-hydrogen peroxide or percarbonate, and a water-soluble solid catalyst such as tungstic acid. Thus, a method of forming a solid phase reaction phase and allowing it to stand in the reaction phase for oxidation is disclosed. In addition, International Publication WO / 2008/093711 discloses that an organic compound, a solid catalyst such as a polyacid catalyst and a hydrogen peroxide solution are dispersed in a solid dispersion phase of powder such as apatite to oxidize the organic compound. (A method using Nonhalite (registered trademark)) is disclosed. However, all of the above methods are methods using a solid catalyst such as tungstic acid or its polyacid.

  As a result of the study, the inventor of the present invention, as for the oxidation of the alicyclic secondary amine compound, by selecting a specific one from the conventionally known solid dispersed phase, that is, hydrotalcite, as the solid dispersed phase, The present invention has been completed by finding that even in a solid phase system, an N-oxyl compound can be produced by oxidation with an oxidizing agent without using a catalyst, and that a high conversion rate and selectivity can be achieved.

The present invention is characterized by using hydrotalcite as a solid dispersed phase. The hydrotalcite used in the method of the present invention is the formula (M ²⁺ ) _1-x (M ³⁺ ) _x (OH) ₂ (A ⁿ⁻ ) _{x / n} · aH ₂ O (wherein M ²⁺ is a divalent metal ^{ion, M 3+} is a trivalent metal ^{ion, a n-represents} an n-valent anion, and x and a respectively 0 <x <0.5,0 ≦ a < 1 range At least one of the compounds represented by

Hydrotalcite is a kind of naturally occurring clay mineral, but it precipitates the target product by adjusting the pH to an appropriate value by adding an alkali metal such as sodium hydroxide to an aqueous solution of a predetermined metal salt such as metal nitrate. Hydrotalcite prepared by a method (hydrothermal method) using a so-called “hydrothermal synthesis reaction” in which a predetermined metal oxide is heated to about 500 ° C. in water (hydrothermal method) is also suitable in the present invention. Used for. For example, synthetic hydrotalcite synthesized from MgO / Al ₂ O ₃ and used as an antacid or the like can also be used as a solid dispersed phase in the present invention.

When the hydrotalcite is synthesized from MgO and Al ₂ O ₃ , if a MgO / Al ₂ O ₃ used in the synthesis is in the range of about ₃ to 8, a more excellent conversion rate can be obtained. Since it is obtained, it is preferable. In a conventional oxidation reaction of an organic compound in a solid phase system, magnesium oxide, alumina, apatite, etc. can be used as a solid dispersion phase in addition to hydrotalcite. However, in the present invention, when magnesium oxide, alumina, apatite, or the like is used, the intended effect, that is, high conversion and selectivity cannot be achieved.

  Examples of the alicyclic secondary amine compound used as a raw material in the present invention include compounds represented by the following formula (1).

  In formula (1), R1, R2, R3 and R4 represent hydrogen or an alkyl group or alkenyl group having about 1 to 10 carbon atoms. In particular, the present invention can be suitably applied when R1, R2, R3, or R4 represents hydrogen or a lower alkyl group such as methyl, ethyl, propyl, or butyl. R1 and R3 may combine to form a ring, or R5 may be an alkyl group (alkylene group) and R1, R3, and R5 may combine to form a ring. Also, the present invention can be preferably applied.

  R5 represents a monovalent group, and specific examples thereof include an alkyl group such as a hydroxyl group, an amino group, and a methyl group, and an alkenyl group such as a carbonyl group, a nitro group, a sulfone group, and a vinyl group. Further, as described above, R1 and R3 and R5 may be bonded to form a ring.

  The present invention is characterized in that an oxidizing agent is dispersed in a solid dispersed phase composed of hydrotalcite together with an alicyclic secondary amine compound as a raw material compound, and an oxidation reaction is performed in a solid phase system or a state close to a solid phase system. And Although it is possible to add a small amount of water, other liquid medium, or other solvent to the reaction system, the range of the addition amount is a range in which a solid phase system or a state close to a solid phase system is maintained. The same applies when using a solution such as aqueous hydrogen peroxide as the oxidizing agent, and adding the oxidizing agent so that the amount of the solvent such as water is within the range where the solid phase system or a state close to the solid phase system is maintained. It is necessary to adjust the amount and concentration of the solution. When the amount of water or other liquid medium added is large and the reaction raw material or solid dispersion phase is dispersed in the liquid phase, the object of the present invention is not achieved. Also, in order to facilitate post-treatment after the reaction and reduce the environmental burden, it is preferable not to add an organic solvent to the reaction system, and it is preferable to carry out the reaction in a solid phase system.

  The invention according to claim 2 is the method for producing an alicyclic N-oxyl compound according to claim 1, wherein the alicyclic secondary amine compound is a compound having a 2-azaadamantane skeleton. is there. The invention according to claim 3 is the production of an alicyclic N-oxyl compound according to claim 1, wherein the alicyclic secondary amine compound is tetramethylpiperidine or hydroxytetramethylpiperidine. Is the method.

  Examples of the alicyclic secondary amine compound represented by the formula (1) include an aliphatic secondary amine having a 6-membered ring structure such as a compound having an azaadamantane skeleton or a compound having a piperidine skeleton. it can. More specifically, 2-azaadamantane represented by the formula (2), tetramethylpiperidine represented by the formula (3) or hydroxytetramethylpiperidine represented by the formula (4) can be exemplified, and these The present invention is suitably applied to the alicyclic secondary amine compound.

  As the alicyclic secondary amine compound used as a raw material in the present invention, in addition to the compound represented by the formula (1), an aliphatic 2 having a 5-membered ring structure such as a compound having a pyrrolidine skeleton or a pyrroline skeleton. A class amine etc. can also be mentioned. It may be an alicyclic compound having two or more secondary amine groups, such as a compound having an imidazolidine skeleton. A compound having an oxazolidine skeleton may also be used.

  The invention described in claim 4 is characterized in that the oxidizing agent is selected from the group consisting of a percarbonate, a hydrogen peroxide solution, and a urea-hydrogen peroxide complex. A process for producing the alicyclic N-oxyl compound according to claim 1.

  Examples of the oxidizing agent used in the present invention include aqueous hydrogen peroxide, sodium percarbonate, urea-hydrogen peroxide complex, and sodium perborate powder. Hydrogen peroxide is used as hydrogen peroxide, but has the advantage that only water is produced as its high oxygen content and by-product. However, when the concentration of the hydrogen peroxide solution is high, there is a danger in handling, while when the concentration of the hydrogen peroxide solution is low, it is necessary to add a large amount of the hydrogen peroxide solution, and the solid phase system or solid solution is required. It may not be possible to maintain a state close to a phase system. In order to maintain a solid phase system or a state close to a solid phase system, a hydrogen peroxide solution having a concentration of 25% or more is preferable, and a hydrogen peroxide solution having a concentration of 25 to 45% is preferably used in consideration of handling safety. .

  The urea-hydrogen peroxide complex is used as a powder, and has an advantage that it is easy to handle during the reaction and has high safety as compared with the hydrogen peroxide solution.

  Invention of Claim 5 is a manufacturing method of the alicyclic N-oxyl compound of Claim 4 whose said oxidizing agent is sodium percarbonate.

  Sodium percarbonate is an adduct of sodium carbonate and hydrogen peroxide (sodium carbonate added with 1.5 moles of hydrogen peroxide), which is easily dissolved in water and dissolved in water. It becomes an aqueous solution of sodium carbonate. It is mainly used as a mild non-chlorine bleach and is also included in commercial household detergents, making it highly safe. And like a urea-hydrogen peroxide complex, it is used as a powder and has the advantage that the handling at the time of reaction is easy and safety | security is high compared with hydrogen peroxide solution. Furthermore, it is preferable to use sodium percarbonate as an oxidizing agent because the conversion rate and selectivity can be further increased.

  Sodium percarbonate and urea-hydrogen peroxide complex are solid powders, safe as long as they are sealed and stored at room temperature, are much easier to handle than hydrogen peroxide, and are subject to transportation restrictions. There is also an advantage of not. Furthermore, it is also preferable in that it is easy to maintain a solid phase system of an oxidation reaction system or a state close to a solid phase system.

  The particle size of the solid powder of sodium percarbonate or urea-hydrogen peroxide complex is not particularly limited, and commercially available particles having a particle size of about 1 μm to 1000 μm can be used, and a granulated product can also be used. it can. From the viewpoint of improving the reaction rate, those having a small particle size are preferred.

  In the invention according to claim 6, the addition amount of the oxidizing agent is 2 to 10 times mol with respect to the alicyclic secondary amine compound in terms of the amount of hydrogen peroxide contained in the oxidizing agent. It is a manufacturing method of the alicyclic N-oxyl compound of Claim 4 or Claim 5 characterized by the above-mentioned.

  The amount of the oxidizing agent added is suitably in the range of 2 to 10 moles per mole of the alicyclic secondary amine compound in terms of the amount of hydrogen peroxide contained in the oxidizing agent. Here, when the oxidizing agent is hydrogen peroxide solution, the number of moles of hydrogen peroxide contained in the hydrogen peroxide solution is “the amount of oxidizing agent converted to the amount of hydrogen peroxide contained in the oxidizing agent. In the case of a percarbonate or urea-hydrogen peroxide complex, the number of moles of hydrogen peroxide constituting the percarbonate or urea-hydrogen peroxide complex is contained in the oxidizing agent. The amount of oxidant added in terms of the amount of hydrogen peroxide ”. For example, 1 mole of sodium percarbonate contains 1.5 moles of hydrogen peroxide, so that 1.5 times the amount of sodium percarbonate added (number of moles) is the amount of oxidizing agent added (moles) converted to the amount of hydrogen peroxide. Number).

  When the addition amount of the oxidizing agent is less than 2 moles with respect to 1 mole of the alicyclic secondary amine compound in terms of the amount of hydrogen peroxide contained in the oxidizing agent, high conversion and selectivity are obtained. It becomes difficult. On the other hand, when the amount exceeds 10 moles, the reaction volume increases, so that the reaction rate does not increase and the treatment cost of unreacted hydrogen peroxide increases. Also, if the oxidizing agent is hydrogen peroxide solution and the amount added exceeds 10 moles, if the concentration of hydrogen peroxide solution is low, the reaction system in a solid phase system or a state close to a solid phase system is maintained. If the concentration is increased, the safety of handling is impaired.

  The invention according to claim 7 is characterized in that the addition amount of the solid dispersed phase is 0.4 to 2.0 g per 1 mmol of the alicyclic secondary amine compound. The manufacturing method of the alicyclic N-oxyl compound of any one of these.

  If the amount of the solid dispersed phase added is less than 0.4 g with respect to 1 mmol of the alicyclic secondary amine compound, the reaction is slow, while if it exceeds 2 g, the productivity tends to decrease. The optimum amount is selected.

The invention according to claim 8 is a mixture of an alicyclic secondary amine compound and an oxidizing agent in a solid dispersion phase comprising hydrotalcite, and the alicyclic secondary amine compound is mixed in the solid dispersion phase. Oxidation step,
After the oxidation, a step of extracting the solid dispersed phase with an organic solvent that dissolves the alicyclic N-oxyl compound,
A step of recovering the alicyclic N-oxyl compound from the extract with the organic solvent, a step of washing the solid dispersion phase after the extraction, and an alicyclic secondary amine compound and oxidation in the solid dispersion phase after the water washing. It is a method for producing an alicyclic N-oxyl compound, comprising a step of mixing an agent and oxidizing the alicyclic secondary amine compound in the solid dispersed phase.

After the manufacturing method of the alicyclic N-oxyl compound which is invention of the said claim is performed for this manufacturing method,
The reaction product, the alicyclic N-oxyl compound, is extracted and recovered from the solid dispersed phase with an organic solvent,
The solid dispersion phase after extraction with the organic solvent is washed with water to remove the decomposition product of the oxidant remaining in the solid dispersion phase (or sodium carbonate if the oxidizer is sodium percarbonate)
In the solid dispersion phase after washing (and drying), an alicyclic secondary amine compound and an oxidizing agent are newly added, and an alicyclic N-oxyl compound is formed by oxidation of the alicyclic secondary amine compound. The manufacturing system is characterized by repetition.

  The alicyclic N-oxyl compound produced by the oxidation reaction in the solid dispersed phase can be recovered by extraction with an organic solvent. Specifically, by extracting the solid dispersion phase with an organic solvent, separating the solid dispersion phase and the extract with the organic solvent by filtration, and removing the organic solvent from the extract by distillation or the like, highly selective N -An oxyl compound can be obtained with a high yield. In conventional liquid phase reactions, it is often difficult to separate the two phases of the aqueous phase and the organic phase in the post-treatment operation. From the separated organic phase, hydrogen peroxide is removed, washed with water, and dried. It was necessary to distill off the organic solvent. Therefore, according to the production method of the present invention, an N-oxyl compound can be obtained more efficiently than a conventional liquid phase reaction from an alicyclic secondary amine compound as a raw material and an oxidizing agent such as sodium percarbonate.

  In this production system, the solid dispersed phase (hydrotalcite powder) is reused. That is, when the N-oxyl compound is extracted with an organic solvent, the unreacted alicyclic secondary amine compound (raw material) is also extracted with the organic solvent. Therefore, the solid dispersed phase after extraction contains an oxidizing agent, And a decomposition product of the oxidizing agent (when the oxidizing agent uses sodium percarbonate, sodium carbonate, hydrogen peroxide, water). Then, reaction by-products (such as sodium carbonate when sodium percarbonate is used as the oxidizing agent) and unreacted oxidizing agents (such as sodium percarbonate) can be easily removed by washing with water. Therefore, if the solid dispersion phase washed with water is dried, it can be set as the hydrotalcite powder which does not contain by-products, such as sodium carbonate, and can be reused as a solid dispersion phase.

  That is, according to this alicyclic N-oxyl compound production system, a series of simple operations of “reaction” — “product extraction / filtration” — “water washing / drying of a solid dispersed phase” allows The N-oxyl compound can be produced with high yield and high selectivity, and the solid dispersed phase can be reused, and the production of the alicyclic N-oxyl compound is repeated by adding a raw material compound to the solid dispersed phase. Can do. And it can be set as the powder reaction system which can manufacture an N- oxyl compound by repeating said series of operation by using a reaction container with a temperature control, filtration, and a drying function.

  Further, if sodium percarbonate is produced from the recovered sodium carbonate and hydrogen peroxide, it is possible to eliminate or reduce the amount of newly added sodium percarbonate. When newly added sodium percarbonate is unnecessary, the production of the alicyclic N-oxyl compound can be repeated using only the alicyclic secondary amine compound and hydrogen peroxide. System.

  According to the method for producing an alicyclic N-oxyl compound of the present invention, a solid phase system using a solid dispersed phase or a state close to a solid phase system, preferably a solvent-free solid phase system, and without using a catalyst. An alicyclic N-oxyl compound can be produced by oxidizing an alicyclic secondary amine compound. And although a catalyst is not used, an alicyclic N-oxyl compound can be obtained with high conversion and selectivity. Since the reaction is carried out in a solid phase system or a state close to a solid phase system, the burden of processing a solvent such as water remaining after the step of separating the product and the reaction is small. Further, since no catalyst is used, there is no need to regenerate or reuse the catalyst. Furthermore, the solid dispersed phase can be reused, and a more efficient production method of the alicyclic N-oxyl compound can be achieved.

  Embodiments of the present invention will be described below. Note that the present invention is not limited to the following embodiments. Various modifications can be made without departing from the spirit of the present invention.

  The reaction in the present invention can be carried out by adding hydrotalcite powder to a reaction vessel and further adding a powder of an alicyclic secondary amine compound and an oxidizing agent as substrates and dispersing in the hydrotalcite powder. . When the alicyclic secondary amine compound is solid, it may be mixed with the solid dispersed phase as a solid powder. Alternatively, a solid alicyclic secondary amine compound may be dissolved in a small amount of solvent and then mixed. When the alicyclic secondary amine compound is a large particle or massive solid, the compound is pulverized and added to the reaction vessel. A compound having a large particle size and a hydrotalcite having a large particle size may be mixed outside the reaction vessel and pulverized, and then added to the reaction vessel.

  After adding hydrotalcite powder, alicyclic secondary amine compound and oxidizing agent to the reaction vessel, the alicyclic secondary amine compound and oxidizing agent are uniformly dispersed in the hydrotalcite powder, ensuring that each other You may stir and mix these so that it may contact. However, after stirring and mixing, the reaction may be carried out in a state where the mixture is allowed to stand, and it is not necessary to perform mixing or stirring.

  As the stirring and mixing method, a normal mixing method used for mixing powder (solid) can be adopted. The order of adding the alicyclic secondary amine compound and the oxidizing agent to the reaction vessel is not particularly limited.

  The reaction temperature is usually 30 to 100 ° C, preferably 45 to 70 ° C. If the reaction temperature is too low, the reaction rate tends to decrease. On the other hand, if the reaction temperature is too high, the decomposition of the oxidizing agent proceeds and the oxidation reaction may not sufficiently proceed. The reaction time varies depending on the relationship between the type and amount of the reaction raw material to be used and the reaction temperature, but is usually several minutes or more, and preferably 50 hours or less from the viewpoint of productivity.

  In the method for producing an alicyclic N-oxyl compound of the present invention, after completion of the reaction, the obtained compound can be isolated by extracting with a solvent and distilling off the solvent from the extracted and separated solution. it can. As the solvent, ethyl acetate or a hydrocarbon solvent with a low environmental load can be used. Further, only the target product can be taken out directly from the reaction mixture by heating under reduced pressure.

  After the reaction is completed and the obtained alicyclic N-oxyl compound is isolated as described above, the alicyclic secondary amine compound and the oxidizing agent are added again to the hydrotalcite powder in the reaction vessel. By stirring and mixing, the synthesis reaction of the alicyclic N-oxyl compound can be performed again.

  Hereinafter, the best mode for carrying out the present invention will be described based on examples. In addition, this invention is not limited to a following example, A various change can be added in the same and equivalent range as this invention.

Example 1 [Synthesis of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (hereinafter referred to as “HTEMPO”)]
Hydrotalcite powder (KYOWARD 500SNG, manufactured by Kyowa Chemical Industry Co., Ltd., MgO / Al ₂ O ₃ ratio: 6.0) 2.00 g and alicyclic secondary amine compound (solid substrate) 4-hydroxy-2, 0.314 g (2.00 mmol) of 2,6,6-tetramethylpiperidine powder (compound represented by the above formula (4), hereinafter referred to as “HTEMPR”) was added to a screw-cap test tube. Thereafter, sodium percarbonate (Mitsubishi Gas Chemical Co., Ltd .: SPC-G (powder)) 1.047 g (6.67 mmol, containing 10.0 mmol of H ₂ O ₂ ) was further added, and the reaction mixture in the powder state did. The test tube was shaken and stirred, and then allowed to stand in a thermostat set to 50 ° C. After 48 hours, the powder reaction mixture was extracted with ethyl acetate and filtered. The solvent was distilled off to obtain 0.320 g of a reddish orange solid (crude yield: 92.8%). When this solid was compared with a commercially available product HTEMPO by GC analysis and IR analysis, it was confirmed that the solid was HTEMPO represented by the following formula (5), and the GC conversion (conversion) and GC selectivity ( When the ratio of HTEMPO to the total of HTEMPO and by-product 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-hydroxyl in the product was measured, the conversion was 97% ( 3% was a raw material), and the selectivity was 99% or more.

Example 2 [Synthesis of 4-methacryloxy-2,2,6,6-tetramethylpiperidine-N-oxyl (hereinafter referred to as “MTEMPO”)]
Hydrotalcite powder (KYOWARD 500SNG) 2.00 g and alicyclic secondary amine compound (solid substrate) 4-methacryloxy-2,2,6,6-tetramethylpiperidine powder (represented by the following formula (6) Compound (hereinafter referred to as “MTEMPR”) 0.451 g (2.00 mmol) was added to the screw cap test tube. Thereafter, 0.943 g (6.0 mmol, containing 9.0 mmol of H ₂ O ₂ ) of sodium percarbonate (SPC-G) was further added to obtain a powdery reaction mixture. The test tube was shaken and stirred, and then allowed to stand in a thermostat set to 50 ° C. After 25 hours, the powder reaction mixture was extracted with ethyl acetate and filtered. The solvent was distilled off to obtain 0.453 g (crude yield: 94.2%) of a reddish orange solid. GC analysis and IR analysis of this solid confirmed that it was MTEMPO represented by the following formula (7), and GC conversion and selectivity (4 of MTEMPO and by-products in the product) were confirmed by the following method. -The ratio of MTEMPO to the total of methacryloxy-2,2,6,6-tetramethylpiperidine-N-hydroxyl) was measured, and the conversion was 96% and the selectivity was 93%.

Example 3 [Synthesis of 2-azaadamantane-N-oxyl (hereinafter referred to as “AZADO”)]
Hydrotalcite powder (Kyoward 500SNG) 1.50 g and alicyclic secondary amine compound (solid substrate) 2-azaadamantane (compound represented by the above formula (2), hereinafter referred to as “AZAD”) 0 .133 g (0.969 mmol) of the mixture was ground in a mortar and added to the screw cap test tube. Thereafter, 0.630 g (4.00 mmol, containing 6.0 mmol of H ₂ O ₂ ) of sodium percarbonate (SPC-G) was further added to obtain a powdery reaction mixture. The test tube was shaken and stirred, and then allowed to stand in a thermostat set to 50 ° C. After 24 hours, the powder reaction mixture was extracted with ethyl acetate and filtered. The solvent was distilled off to obtain 0.125 g (crude yield: 84.8%) of a reddish orange solid. When this solid was compared with a standard product by GC analysis and IR analysis, it was confirmed to be AZADO represented by the following formula (8). When the GC conversion was measured by the following method, the conversion was 100% (by-product 2-azaadamantane-N-hydroxyl 3%. Therefore, the selectivity was 97%).

[Measurement of GC conversion and GC selectivity]
A solution obtained by extracting the reaction mixture with an organic solvent or a crude product obtained by distilling off the solvent was subjected to GC analysis according to the procedure shown below to determine GC conversion and selectivity. Shimadzu FID gas chromatograph (capillary column Inert Cap 5 (0.25 mm ID x 15 m, df = 0.25 μm)) was used for GC measurement.
(GC analysis procedure)
1. The relative molar sensitivity between the raw material and the target product under the conditions for GC measurement is determined. All other by-products are considered to have the same relative molar sensitivity as the desired product.
2. The GC measurement is performed, and the relative molar yield of the raw material, the target product, and the by-product is converted from the measurement result (the peak area ratio of the chromatogram) and the relative molar sensitivity.
3. The GC conversion and GC selectivity are calculated according to the following equations.
GC conversion = [(sum of relative molar yields of target product and by-products) / (sum of relative molar yields of raw materials, target products and by-products)] × 100
GC selectivity = [relative molar yield of target product / (sum of relative molar yields of target product and byproduct)] × 100

Examples 4 to 7, Comparative Example 1 [Production of HTEMPO]
The amount of hydrotalcite powder was changed as shown in Table 1, and HTEMPR was 0.5 mmol, and the amount of sodium percarbonate was 1.0 mmol (2 mol per HTEMPR, including 1.5 mmol of H ₂ O ₂ ). The reaction was carried out in the same manner and under the same conditions as in Example 1, and the conversion rate and selectivity of HTEMPO after 24 hours of reaction (standing) and 48 hours of reaction (standing) were measured. The results are shown in Table 1.

  As shown in Table 1, when the amount of hydrotalcite added is 0.5 g with respect to 1 mmol of HTEMPR (Example 4), excellent conversion and selectivity are obtained. In particular, when the amount of hydrotalcite added is 1.0 g or more, a higher conversion rate and selectivity are obtained, but in the case of 2.0 g compared to the case of 1.5 g (Example 6) (implementation) In the case of Example 7), the conversion rate is lowered. From this result, it is considered that the amount of hydrotalcite added is preferably in the range of 0.4 to 2 g with respect to 1 mmol of HTEMPR.

Examples 8 to 12 [Production of HTEMPO]
The reaction was carried out in the same manner and under the same conditions as in Example 5 except that the amount of sodium percarbonate was changed as shown in Table 2. After 24 hours of reaction (standing) and 48 hours of reaction (standing) (optional) The conversion rate and selectivity of HTEMPO after 48 hours reaction (standing) were measured. The results are shown in Table 2.

  As shown in Table 2, when the amount of sodium percarbonate added is 1.5 times the mol of the alicyclic secondary amine compound in terms of the amount of hydrogen peroxide contained (implementation) Example 8) In the reaction at 50 ° C., the conversion is 42% at 24 hours, and the conversion is 61% even at 72 hours. On the other hand, when the amount of sodium percarbonate added exceeds 3 times mol, a high conversion rate is obtained. From this result, it is considered that the addition amount of the oxidizing agent is preferably 2 times mol or more with respect to the alicyclic secondary amine compound in terms of the amount of hydrogen peroxide contained therein.

Examples 13 to 16 [Production of HTEMPO]
The reaction temperature was changed as shown in Table 3, and the same method as in Example 5 except that the amount of sodium percarbonate was 2.0 mmol (4 mol times HTEMPR, 3.0 mmol of H ₂ O ₂ was included). The reaction was conducted under the conditions, and the conversion rate and selectivity of HTEMPO were measured. The results are shown in Table 3.

  As shown in Table 3, in the reaction at 40 ° C., even when the HT ratio is 1.0 and the SPC ratio is 4 (6 in terms of the amount of hydrogen peroxide), conversion in 24 hours is possible. The rate is 42% and the conversion rate is 67% even in 72 hours. On the other hand, when the reaction temperature is 50 ° C., the conversion rate exceeds 80% even in 24 hours. From this result, it is considered that the reaction temperature is preferably 45 ° C. or higher.

Examples 17 to 19 and Comparative Examples 2 to 4 [Production of HTEMPO]
The reaction was carried out in the same manner and under the same conditions as in Example 5 except that the solid dispersion phase shown below was used, and the conversion rate and selectivity of HTEMPO were measured. The results are shown in Table 4.

[Solid dispersed phase used]
1) Hydrotalcite: MgO / Al ₂ O ₃ = 6.0 (Kyoward 500 SNG: In Table 4, it is expressed as HT1)
2) Hydrotalcite: MgO / Al ₂ O ₃ = 4.6 (represented as HT2 in Table 4)
3) Hydrotalcite: MgO / Al ₂ O ₃ = 2.5 (represented as HT3 in Table 4)
4) Alumina (Al ₂ O ₃ ): Merck, Alumina 90 (specific surface area (BET method): 110 m ² / g)
5) Magnesia (MgO): manufactured by Kyowa Chemical Industry Co., Ltd., Kyowa Mag 150 (specific surface area (BET method): 140 m ² / g)
6) Hydroxyapatite: manufactured by Sekisui Chemical Co., Ltd., apamicron (specific surface area (BET method): 74 m ² / g)

As shown in Table 4, excellent conversion was obtained only when hydrotalcite was used as the solid dispersed phase, and excellent conversion was obtained when alumina, magnesia, and hydroxyapatite were used. It is not done. Therefore, it is considered necessary to use hydrotalcite as the solid dispersed phase in order to achieve the effects of the present invention. Further, in the hydrotalcite, when the ratio of MgO / Al ₂ O ₃ is 2.5 (Example 19), a high conversion rate is not obtained. From this result, it is considered that hydrotalcite having a MgO / Al ₂ O ₃ ratio of 3 or more is preferable.

Example 20 [Production of HTEMPO]
0.75 g of hydrotalcite powder (Kyoward 500 SNG) and 0.0788 g (0.5 mmol) of HTEMPR powder were added to the screw test tube. Thereafter, 0.314 g (2.0 mmol, containing 3.0 mmol of H ₂ O ₂ ) of sodium percarbonate (SPC-G) was further added to obtain a powdery reaction mixture. The test tube was shaken and stirred, and then allowed to stand in a thermostat set to 50 ° C. After 48 hours, the powder reaction mixture was extracted with ethyl acetate and filtered. The production | generation of HTEMPO was confirmed similarly to Example 1, and when GC conversion rate was measured, it was 99%.

Example 21 [Production of HTEMPO]
Except that 3.0 mmol of sodium perborate was used instead of 2.0 mmol of sodium percarbonate, the reaction was carried out in the same manner and under the same conditions as in Example 20, and the GC conversion rate of HTEMPO was measured to be 29%. .

  The results of Example 21 show that the present invention can be practiced when sodium perborate is used as the oxidizing agent instead of sodium percarbonate. However, the comparison between Examples 20 and 21 shows that the conversion rate when sodium perborate is used is lower than that when sodium percarbonate is used, and sodium percarbonate is preferable among the solid oxidizing agents. Has been.

Example 22 [Production of HTEMPO]
A mixture of 0.25 g of hydrotalcite powder (Kyoward 500 SNG) and 0.25 mmol of HTEMPR was pulverized in a mortar and added to a screw cap test tube. Thereafter, 0.833 mmol of sodium percarbonate (SPC-G) (containing 1.25 mmol of H ₂ O ₂ ) was further added to obtain a powdery reaction mixture. The test tube was shaken and stirred, and then allowed to stand in a thermostat set to 50 ° C. After 48 hours, the powder reaction mixture was extracted with ethyl acetate and filtered. The production of HTEMPO was confirmed in the same manner as in Example 1, and the conversion rate (Conversion) was measured. As a result, it was 97% and the selectivity was 99%.

Comparative Example 5 [Production of HTEMPO]
Hydroxyapatite (HAp) 0.50 g and HTEMPR (0.50 mmol) powder were added to the screw cap test tube. Thereafter, a catalyst (tungstic acid [H ₂ WO ₄ ] 0.05 mmol: 10 mol% with respect to HTEMPR) was further added to form a reaction mixture in a powder state. Furthermore, 35% hydrogen peroxide solution (1.50 mmol) was added, the test tube was shaken and stirred well, and then allowed to stand at 25 ° C. After standing for 24 hours, extraction with a solvent was performed in the same manner as in Example 1 and GC analysis was performed. As a result, it was confirmed that HTEMPO was produced at a conversion rate of 97% and a selectivity rate of 99%.

Comparative Example 6 [Production of HTEMPO]
0.50 g of calcium carbonate (CaCO ₃ : reagent) and HTEMPR (0.50 mmol) powder were added to a screw-cap test tube. Thereafter, a catalyst (tungstic acid [H ₂ WO ₄ ] 0.05 mmol: 10 mol% with respect to HTEMPR) was further added to form a reaction mixture in a powder state. Further, urea-hydrogen peroxide complex (1.50 mmol, manufactured by Aldrich) was added, and the test tube was shaken and stirred well, and then allowed to stand at 35 ° C. After standing for 8 hours, extraction with a solvent was conducted in the same manner as in Example 1 and GC analysis was performed. As a result, it was confirmed that HTEMPO was produced at a conversion rate of 95% and a selectivity rate of 98%.

  Comparative Examples 5 and 6 are methods using a catalyst (tungstic acid). As shown in the above examples, according to the present invention, HTEMPO can be obtained without using a catalyst (tungstic acid).

Example 23 [Production of TEMPO]
Hydrotalcite powder (KYOWARD 500SNG) (1.00 g) was added to a screw-cap test tube, and alicyclic secondary amine compound 2,2,6,6-tetramethylpiperidine (expressed by the above formula (3)) was added thereto. 0.157 g (1.1 mmol), which is referred to as “TEMPR” hereinafter, was impregnated. Thereafter, 0.350 g (2.2 mmol, containing 3.3 mmol of H ₂ O ₂ ) of sodium percarbonate (SPC-G) was further added to obtain a powdery reaction mixture. The test tube was shaken and stirred, and then allowed to stand in a thermostat set at 50 ° C. for 17 hours. The powder reaction mixture was then extracted with ethyl acetate and filtered. The solvent was distilled off to obtain 0.137 g of a reddish brown solid (crude yield 81.6%). When GC analysis and IR analysis were compared with a commercially available product TEMPO, it was confirmed that it was TEMPO, and its GC conversion rate and GC selectivity were measured by the same method as in the above Example. As a result, the GC conversion rate was 100. The GC selectivity was 99% or more.

Example 24 [Production of TEMPO]
Except that the standing time in the incubator set at 50 ° C. was changed to 10 hours, the same reaction as in Example 23 was performed, and it was confirmed that TEMPO was obtained, and the GC conversion rate was The GC selectivity was 99%.

Example 25 [Production of TEMPO]
The standing time in the incubator set at 50 ° C. was changed to 10 hours, and the amount of sodium percarbonate (SPC-G) was changed from 2.0 mmol to 3.3 mmol (containing 5.0 mmol of H ₂ O ₂ ). Except for this change, the same reaction as in Example 23 was carried out. As a result, it was confirmed that TEMPO was obtained, the GC conversion was 98%, and the GC selectivity was 99%.

Comparative Example 7 [Production of TEMPO]
A solid mixture (Nonhalite®-WP) 1.0 g and TEMPR (1.0 mmol) consisting of hydroxyapatite (HAp) and catalyst (CetylPy) ₃ [PW ₁₂ O ₄₀ ] 0.061 g (0.020 mmol), and 35% hydrogen peroxide solution (3.0 mmol) was added, the test tube was shaken and stirred well, and then allowed to stand at 50 ° C. After standing for 10 hours, the GC conversion rate and GC selectivity were measured in the same manner as in Example 23. As a result, the GC conversion rate was 85% and the GC selectivity was 94%.

  The results of Examples 24 and 25 indicate that TEMPO (solid) can also be produced from TEMPR (liquid) according to the present invention, as in the case of producing HTEMPO (solid) from HTEMPR (solid). Further, by comparing Examples 24 and 25 with Comparative Example 7, according to the method of the present invention, conversion superior to the method conventionally applied to the oxidation of other organic compounds (Comparative Example 7: so-called nonhalite method). It has been shown that rate and selectivity can be obtained.

Examples 26 to 28 [Production of TEMPO]
1.0 mmol of TEMPR was soaked in 1.0 g of hydrotalcite powder (Kyoward 500 SNG). Thereafter, the oxidizing agent shown in Table 5 was further added in the amount shown in Table 5 (in each case, 3.0 mmol in terms of hydrogen peroxide) to obtain a powdery reaction mixture. The test tube was shaken and stirred, and then allowed to stand in a thermostat set to 50 ° C. A portion of the powder reaction mixture was taken at predetermined time intervals and extracted with ethyl acetate. Thereafter, the GC conversion was measured in the same manner as in Example 23. Table 5 shows the measurement results.

  From the results of Examples 26 to 28, it is shown that hydrogen peroxide solution and urea-hydrogen peroxide complex can be used as the oxidizing agent in addition to the percarbonate. However, since a higher conversion rate is obtained when sodium percarbonate is used than when other oxidizing agents are used, it is considered that percarbonate is preferable as the oxidizing agent.

Examples 29 to 33 [Production of AZADO]
Hydrotalcite powder (Kyoward 500 SNG) in an amount shown in Table 6 and AZAD powder 0.25 mmol of an alicyclic secondary amine compound (solid substrate) were mixed and added to a screw-cap test tube. Thereafter, sodium percarbonate (SPC-G) was further added in the amount shown in Table 6 to obtain a powdery reaction mixture. The test tube was shaken and stirred, and then allowed to stand in a thermostat set to 50 ° C. for the time shown in Table 6. A portion of the powder reaction mixture was taken at predetermined time intervals and extracted with ethyl acetate. When the extract was compared with a standard product by GC, it was confirmed to be AZADO. The GC conversion rate and GC selectivity were measured by the same method as in the previous example. The results are shown in Table 6.

Comparative Example 8 [Production of AZADO]
0.25 g of hydroxyapatite (HAp) and 0.25 mmol of AZAD powder were added to the screw test tube and mixed. Thereafter, a catalyst (tungstic acid [H ₂ WO ₄ ] 0.025 mmol: 10 mol% with respect to AZAD) was further added to form a reaction mixture in a powder state. Further, 35% hydrogen peroxide (1.00 mmol) was added, and the test tube was shaken and stirred well, and then allowed to stand at 25 ° C. After standing for 3 hours, the product was isolated in the same manner as in Example 29 and confirmed to be AZADO. When the GC conversion rate and GC selectivity were measured by the same method as in the above Example, the GC conversion rate was 81% and the GC selectivity was 93%.

Comparative Example 9 [Production of AZADO]
Except that the addition amount of 35% hydrogen peroxide water was changed from 1.00 mmol to 0.75 mmol and the standing time was changed from 3 hours to 12 hours, the same reaction as in Comparative Example 8 was performed. The GC selectivity was 96%.

  From the results of Examples 29 to 33, it is shown that AZADO can also be produced from AZAD according to the present invention, as in the case of producing HTEMPO from HTEMPR. In addition, the results of Comparative Examples 8 and 9 show that the GC conversion can be obtained only about 80% by the method conventionally applied to the oxidation of the organic compound, but the results of Examples 29 to 33 are obtained. From the results, it is shown that an excellent conversion rate close to 100% can be obtained according to the method of the present invention.

Example 34 [Synthesis of HTEMPO]
Hydrotalcite powder (KYOWARD 500SNG, manufactured by Kyowa Chemical Industry Co., Ltd., MgO / Al ₂ O ₃ ratio: 6.0) 2.01 g and alicyclic secondary amine compound 4-hydroxy-2,2,6,6 -0.313 g (2.00 mmol) of tetramethylpiperidine (HTEMPR) powder was added to the screw test tube. Thereafter, sodium percarbonate (Mitsubishi Gas Chemical Co., Ltd .: SPC-G (powder)) 1.047 g (6.67 mmol, containing 10.0 mmol of H ₂ O ₂ ) was further added, and the reaction mixture in the powder state did. The test tube was shaken and stirred, and then allowed to stand in a thermostat set to 70 ° C. After 10 hours, the powder reaction mixture was extracted with ethyl acetate and filtered. The solvent was distilled off to obtain 0.300 g of a reddish orange solid (crude yield: 87.9%). The GC conversion was 95% (4% was a raw material), and the selectivity was 99% or more.

Example 35 [First reuse of hydrotalcite]
From the solid powder remaining after the ethyl acetate extraction in Example 34, the sodium percarbonate oxidizing agent and sodium carbonate derived therefrom were removed by washing with water. Drying was performed at 100 ° C. for several hours to obtain 1.940 g of hydrotalcite powder. Using this recovered hydrotalcite powder, HTEMPO was again synthesized by a powder reaction in the same manner. That is, 0.315 g (2.00 mmol) of HTEMPR and 1.048 g of sodium percarbonate (6.67 mmol, containing 10.0 mmol of H ₂ O ₂ ) were added to this powder to obtain a reaction mixture in a powder state. . It left still at 70 degreeC for 10 hours. The same operation as above was performed to obtain 0.327 g (crude yield: 94.7%) of a reddish orange solid. The GC conversion was 86% (13% was the raw material), and the selectivity was 99% or more.

Example 36 [Second reuse of hydrotalcite]
In the same manner as in Example 35, 1.792 g of hydrotalcite powder was recovered from the solid powder remaining after extraction. To this, 0.283 g (1.80 mmol) of HTEMPR and 0.939 g of sodium percarbonate (6.00 mmol, containing 9.0 mmol of H ₂ O ₂ ) were added to obtain a reaction mixture in a powder state. It left still at 70 degreeC for 10 hours. The same operation was performed to obtain 0.292 g (crude yield: 94.3%) of a reddish orange solid. The GC conversion was 91% (9% was the raw material), and the selectivity was 99% or more.

Claims (8)

  An oil characterized by mixing an alicyclic secondary amine compound and an oxidizing agent in a solid dispersed phase comprising hydrotalcite, and oxidizing the alicyclic secondary amine compound in the solid dispersed phase. A method for producing a cyclic N-oxyl compound.   The method for producing an alicyclic N-oxyl compound according to claim 1, wherein the alicyclic secondary amine compound is a compound having a 2-azaadamantane skeleton.   The method for producing an alicyclic N-oxyl compound according to claim 1, wherein the alicyclic secondary amine compound is tetramethylpiperidine or hydroxytetramethylpiperidine.   4. The alicyclic group according to claim 1, wherein the oxidizing agent is selected from the group consisting of a percarbonate, a hydrogen peroxide solution, and a urea-hydrogen peroxide complex. 5. A method for producing an N-oxyl compound.   The method for producing an alicyclic N-oxyl compound according to claim 4, wherein the oxidizing agent is sodium percarbonate.   The amount of the oxidant added is 2 to 10 times the mol of the alicyclic secondary amine compound in terms of the amount of hydrogen peroxide contained in the oxidant. The manufacturing method of the alicyclic N-oxyl compound of Claim 4 or Claim 5.   7. The fat according to claim 4, wherein the amount of the solid dispersed phase added is 0.4 to 2.0 g based on 1 mmol of the alicyclic secondary amine compound. A method for producing a cyclic N-oxyl compound. Mixing a cycloaliphatic secondary amine compound and an oxidant in a solid dispersion phase comprising hydrotalcite, and oxidizing the cycloaliphatic secondary amine compound in the solid dispersion phase;
After the oxidation, a step of extracting the solid dispersed phase with an organic solvent that dissolves the alicyclic N-oxyl compound,
A step of recovering the alicyclic N-oxyl compound from the extract, a step of washing the solid dispersion phase after extraction, and an alicyclic secondary amine compound and an oxidizing agent in the solid dispersion phase after washing with water. And a step of oxidizing the alicyclic secondary amine compound in the solid dispersed phase. A method for producing an alicyclic N-oxyl compound, comprising: