JP6282005B2 - Improved process for producing oxidation products by photooxygen oxidation - Google Patents

Description

  The present invention generally relates to a method for producing a compound by oxidation of an organic compound, and particularly relates to a production method using photooxygen oxidation.

  The photo-oxygen oxidation reaction performed by irradiating an organic compound solution with light in an oxygen (air) atmosphere is well known, and can be applied to the production of various oxidation products. The photooxygen oxidation reaction is an oxidation reaction with singlet oxygen, and is performed by adding a photosensitizer as a catalyst for the necessity of promoting the reaction. In general, a photosensitizer transfers energy to the ground state oxygen (triplet) when it is irradiated with light and becomes a singlet excited state and quickly returns to triplet oxygen. Exciting action to promote photo-oxygen oxidation reaction.

  However, photosensitizers are expensive and cause a significant increase in the production cost of the target product, so they are not suitable for use on an industrial scale. Moreover, since it is also an impurity for the target product, it is preferable to reduce the amount used if possible, and even more preferable if it is not necessary to use it.

  As for the oxidation of sulfides, oxidation by singlet oxygen is not limited to sulfoxide but is further oxidized to sulfone, giving both of them as a result, and selective oxidation that terminates the reaction with sulfoxide is not possible. It is difficult (Non-Patent Document 1). As another method, even in the general synthesis method of sulfoxide by oxidizing sulfide with peroxide, the oxidation proceeds to sulfone even if selective oxidation to sulfoxide is aimed at by controlling the number of equivalents of peroxide. Therefore, selective synthesis of sulfoxide is not easy (Non-patent Document 2).

  Although not in the field of photo-oxygen oxidation reaction, if bubbles with a diameter of several tens of μm to several hundreds of nanometers called microbubbles or micronanobubbles are used, the oxidation reaction of alcohol with oxygen or the catalytic hydrogenation reaction using a catalyst such as Pd However, it is known that it proceeds efficiently at room temperature and normal pressure without requiring mechanical stirring (Non-Patent Documents 3 to 7). Devices for generating such fine bubbles are also known and are commercially available from multiple manufacturers.

  As for micro-nano bubbles, while a solution containing 2-ethylanthraquinone is allowed to flow through the microreactor, a gas containing hydrogen is introduced into the solution in the form of microbubbles through a filtration membrane in the microreactor. A method is also known in which a solution in which bubbles are dispersed is introduced into an immobilized catalyst column and reduced to 2-ethylanthrahydroquinone (Non-patent Document 8).

To, W.-P .; Liu, Y .; Lau, T.-C .; Che, C.-M. Chem.-Eur. J. 2013, 19 (18), 5654-5664. Crich, D .; Banerjee, A .; Yao, Q. J. Am. Chem. Soc. 2004, 126 (45), 14930-14934. Takuma Sakai et al., Chubu Chemical Association Association Autumn Meeting Sponsored Proceedings, Vol. 43, p. 127 (2012) Takuma Sakai et al., Abstracts of Summer Symposium of Japanese Society for Process Chemistry, Vol.2012, pp.254-255 (2012) Takuma Sakai et al., Abstracts of the Summer Symposium of the Japanese Society for Process Chemistry, Vol. 2012, pp. 137-137 (2012) Masayuki Mase et al., Piping Technology, Vol. 53, No. 5, pp. 48-52 (2011) N. Mase, et al., Chem. Commun, Vol. 47, p. 2086-2088 (2011). J. Tan et al., AIChE Journal, Vol. 58, No. 5, p. 1326-1335 (2012).

  Under the above background, the object of the present invention is to allow the photo-oxidation reaction of organic compounds to proceed at a higher speed and efficiency at room temperature and atmospheric pressure than conventional methods. The object is to provide a method which can also reduce or eliminate the use.

  When the present inventors supply oxygen gas or air used for the reaction in the form of fine bubbles (nanobubbles) having a particle size smaller than 1 μm in the reaction solution in the photo-oxygen oxidation reaction, In addition, the present inventors have found that the photooxygen oxidation reaction can be performed efficiently even if the amount of the photosensitizer used is very small or no photosensitizer is used. Unexpectedly, depending on the relationship between the raw material compound and the target product, the main product can be selected by adjusting the amount of photosensitizer, and furthermore, highly selective oxidation of sulfide to sulfoxide is possible. I also found out. The present invention described below has been completed through further studies based on these findings.

1. An improved production method for producing a product by photo-oxygen oxidation of a raw organic compound, wherein an oxygen-containing gas is injected into the raw organic compound-containing solution under light irradiation in the form of nanobubbles, A production method, wherein the product is obtained by proceeding a photo-oxygen oxidation reaction of the raw organic compound by maintaining a state in which the nanobubbles of the oxygen-containing gas are dispersed in a solution.
2. The production method according to 1 above, wherein the solution contains a photosensitizer.
3. The photosensitizer is selected from the group consisting of rose bengal, methylene blue, eosin Y, fluorescein, p-benzoquino, rubrene, 5,10,15,20-tetraphenylporphine, and a transition metal complex. 1 or 2 above.
4). 4. The production method according to any one of 1 to 3 above, wherein the concentration of the photosensitizer in the solution is 3 mol% or less with respect to the raw material organic compound.
5. The production method according to 1 above, wherein the solution does not contain a photosensitizer.
6). 6. The method according to any one of 1 to 5 above, wherein the light source for light irradiation is selected from a mercury lamp, a halogen lamp, an LED lamp and an incandescent lamp.
7). The raw organic compound (M) and the product (P) have the following combinations:
(i) M: α-terpinene, P: ascaridol and / or p-cymene
(ii) M: R ¹ CH ₂ NH ₂ , P: R ¹ CH═NCH ₂ R ¹
[Wherein, R ¹ represents an aromatic group which may have a substituent. ]
(iii) M: R ¹ CH ₂ NHR ² , P: R ¹ CH═NHR ²
[Wherein, R ¹ is the same as defined above, and R ² represents a saturated hydrocarbon group which may have a substituent or an aromatic group which may have a substituent. ]
(iv) The production method according to any one of 1 to 6 above, which is selected from M: sulfide and P: sulfoxide.
8). 8. The production method according to 7 above, wherein the aromatic ring portion of R ¹ has 6 to 10 carbon atoms.
9. The substituent of R ¹ is selected from the group consisting of R ³ —, R ³ O— and X, where R ³ may be substituted with one or more halogen or hydroxyl groups. The above 7 or 7 represents a saturated hydrocarbon group having 1 to 6 carbon atoms, or a phenyl group which may be substituted with one or more halogens or hydroxyl groups, and X represents halogen. 8. Manufacturing method of 8.
10. R ² represents a saturated hydrocarbon group having 1 to 10 carbon atoms which may have a substituent, or an aromatic group having 6 to 10 carbon atoms which may have a substituent, or R ² represents R The production method according to any one of the above 7 to 9, which represents a saturated hydrocarbon group which may be bonded to ¹ to form a ring.
11. The substituent of R ² is selected from the group consisting of R ⁴ —, RO—, and X, where R ⁴ is the number of carbon atoms that may be substituted with one or more halogen or hydroxyl groups. 1-6 saturated hydrocarbon groups, or a phenyl group optionally substituted by one or more halogens, X represents a halogen or hydroxyl group, Production method.
12 The starting organic compound (M) and the product (P) may have (M) 1,2,3,4-tetrahydroisoquinoline which may have a substituent and (P) substituent 3, 12. The production method according to any one of 7 to 11 above, which is 4-dihydroisoquinoline.
13. The sulfide and sulfoxide are R ⁶ -S—R ⁷ and R ⁶ —SO—R ⁷ , respectively.
[Wherein R ⁶ and R ⁷ are the same or different and each represents a saturated hydrocarbon group which may have a substituent or an aromatic group which may be substituted] The manufacturing method in any one of -12. 14. The production method according to 13 above, wherein the saturated hydrocarbon group has 1 to 10 carbon atoms, and the aromatic ring part of the aromatic group has 6 to 10 carbon atoms.
15. The substituent of R ⁶ or R ⁷ represents R ⁸ —, R ⁸ O— or X, and R ⁸ has 1 to 6 carbon atoms which may be substituted with one or more halogen or hydroxyl groups; 15. The production method according to 14 above, which represents an alkyl group and X represents a halogen or a hydroxyl group.

According to the present invention, in the production of a product by photo-oxygen oxidation of a raw material organic compound, a reaction can be efficiently performed at normal pressure. In addition, heating of the reaction solution (60 ° C., etc.) is not particularly necessary, and it can be performed at room temperature, allowing the reaction to be carried out efficiently even with a very small amount of photosensitizer used. It is even possible not to use a sensitizer. Further, in the present invention, in the case of a raw material compound that gives a plurality of products by photooxygen oxidation, a compound that has been obtained only as a by-product in the past can be selected mainly by selecting conditions such as the type and concentration of the photosensitizer. In addition to providing the potential to be selectively obtained as a product, it allows highly selective oxidation of a wide variety of sulfides to sulfoxides.
Further, according to the present invention, selective oxidation of sulfide to sulfoxide becomes possible.

FIG. 1 is a conceptual diagram of a photo-oxygen oxidation reaction apparatus used in the present invention. FIG. 2 is a graph showing the particle size distribution of bubbles formed by the nanobubble generator.

  In this specification, “nano bubbles” are fine bubbles of gas in a liquid, and the number of bubbles having a particle diameter of 5 nm or more and less than 1000 nm is 90% or more with respect to the total number of bubbles. Preferably, the number of bubbles having a particle size of 50 to 500 nm is 90% or more, more preferably the number of bubbles having a particle size of 50 to 400 nm is 90% or more Say things.

  In this specification, “oxygen-containing gas” means oxygen gas, air, a mixture of oxygen gas and air, an inert gas (that is, a gas that does not affect the photo-oxygen oxidation reaction such as nitrogen), oxygen, and the like. This is a mixed gas.

  In this specification, “light” in “light irradiation” is not particularly limited as long as photo-oxygen oxidation of the raw material organic compound proceeds by the light irradiation. Usually, it may be light including ultraviolet light, but ultraviolet light is not essential. In addition to mercury lamps (high-pressure mercury lamps, low-pressure mercury lamps), halogen lamps, LED lamps, incandescent lamps, and the like can be used as the light source.

  Unlike the thermal reaction, the photo-oxygen oxidation reaction is caused by oxygen molecules excited by light. Therefore, it is not necessary to heat and heat the reaction solution, and the reaction may be performed at room temperature. The temperature of the reaction solution may be, for example, 10 to 30 ° C.

  According to the present invention, there is no need to pressurize the reaction system, and the reaction can proceed rapidly by simply reacting at normal pressure. Of course, if the pressure is applied, the reaction rate can be further increased. Is possible.

  Although depending on the photosensitizer used with the raw material organic compound, according to the present invention, the reaction can proceed promptly even if the photosensitizer is added in a very small amount, so the molar ratio with respect to the amount of the raw organic compound. Thus, for example, the amount of photosensitizer added can be reduced to about 0.01 to 0.001%. Also, depending on the starting organic compound, it is not necessary to use a photosensitizer (for example, oxidation of sulfide to sulfoxide).

In the present invention, any photosensitizer that is conventionally known to be used for photooxygen oxidation can be used. General examples include, but are not limited to, rose bengal, methylene blue, eosin Y, fluorescein, p-benzoquino, rubrene, 5,10,15,20-tetraphenylporphine, and transition metal complexes. Not. Examples of the transition metal complex include [Ru (bpy) ₃ ] ²⁺ complex, [Ir (dtb-bpy) (ppy) ₂ ] ⁺ complex, [Ir (dfppy) ₃ ] complex, and the like. Not.

  In the present invention, the concentration of the raw material organic compound in the solution subjected to the photooxidation reaction is not particularly limited. Therefore, the concentration depends on the solubility of the starting organic compound in the solvent used, the light intensity from the light source used for light irradiation, the degree of attenuation of the excitation light in the solution of the starting organic compound, the solubility of the reaction product, the desired reaction efficiency, the handling It may be set appropriately considering factors such as ease. For example, it may be 0.01 to 0.5M, but is not limited thereto.

  Conventionally, it is known that ascaridol is obtained as a main product and p-cymene is obtained as a by-product by photooxygen oxidation of α-terpinene, but by selecting the type and concentration of the photosensitizer to be added, It has been found by the present inventors that either alkali dol or cymene is efficiently obtained as the main product. For example, when rose bengal or methylene blue is used as a photosensitizer in an amount of, for example, about 15 mol% with respect to α-terpinene, alkali dol can be obtained as a main product according to the present invention as in the prior art. When Rose Bengal is used as a sensitizer in a smaller amount (for example, 1 to 3 mol% with respect to α-terpinene), p-cymene can be obtained as a main product several to several tens of times more than alkali dol. it can. In the photo-oxygen oxidation reaction in the presence of a photosensitizer, the main product that is opposite to the conventional product can be produced by supplying oxygen in the form of nanobubbles. Yes, the mechanism is not clear so far.

According to the present invention, in addition to the production of α-terpinene to ascaridol or p-cymene, for example, the following reaction can be performed with high efficiency.
(1) Production of p-cymene by oxidation of γ-terpinene.
(2) Primary amine R ¹ CH ₂ NH ₂ [R ¹ represents an aromatic group which may have a substituent. Production of imine R ¹ CH═NHR ² by dehydrogenation homocoupling of
Here, R ¹ preferably has an aromatic ring portion having 6 to 10 carbon atoms, and more preferably a phenyl group or a naphthyl group.
As the substituent for the aromatic ring moiety, those selected from the group consisting of R ³ —, R ³ O— and X (halogen) are preferred. Here, R ³ may be substituted with one or two or more halogen or hydroxyl groups, preferably 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, still more preferably 1 to 3 carbon saturated hydrocarbons. Represents a phenyl group which may be substituted with one or more halogen or hydroxyl groups. Halogens that can be used include fluorine, chlorine, bromine, and iodine.
(3) Secondary amine R ¹ CH ₂ NHR ² [R ¹ is as defined above. R ² represents a saturated hydrocarbon group which may have a substituent or an aromatic group which may have a substituent. The production of imine R ¹ CH═NHR ² by dehydrogenation of
Here, R ² may have a substituent, and preferably represents a saturated hydrocarbon group having 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, or a substituted group. Preferably represents an aromatic group having 6 to 10 carbon atoms (for example, a phenyl group or a naphthyl group) or R ² may be bonded to R ¹ to form a ring. A hydrocarbon group (for example, ethylene group) is represented.
The substituent that R ² may have is preferably selected from the group consisting of R ⁴ —, R ⁴ O— and X (halogen), wherein R ⁴ is one or more halogens or 1 to 6 carbon atoms which may be substituted with a hydroxyl group, preferably 1 to 4 carbon atoms, more preferably a saturated hydrocarbon group having 1 to 3 carbon atoms, or one or more halogen or hydroxyl Represents a phenyl group which may be substituted with a group, and X represents halogen. Halogen includes fluorine, chlorine, bromine, and iodine.
(5) Selective oxidation of sulfide to sulfoxide.
Here, the sulfide and sulfoxide are R ⁶ —S—R ⁷ and R ⁶ —SO—R ⁷ , respectively, wherein R ⁶ and R ⁷ are the same or different and may have a substituent. Represents a hydrocarbon group or an optionally substituted aromatic group]. The saturated hydrocarbon group preferably has 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, still more preferably 1 to 4 carbon atoms, and the aromatic group preferably has 6 to 10 carbon atoms. (For example, phenyl group, naphthyl group).
When R ⁶ or ^{which R 7} is substituted, the substituent is ^preferably, R 8 ^-, R 8 O-, a X (halogen) or hydroxyl group, ^{R 8} is one or more It is preferably a saturated hydrocarbon group having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and still more preferably 1 to 3 carbon atoms, which may be substituted with a halogen group or a hydroxyl group.

  The solvent used in the reaction is not particularly limited as long as it can dissolve the starting organic compound to a desired concentration (usually about 0.1M) and can also dissolve the photosensitizer when added. There is no limit. For example, organic solvents such as methanol, ethanol, n-propanol, isopropanol ethyl acetate, acetonitrile, tetrahydrofuran, and a mixture of two or more of these can be easily used, but are not limited thereto.

  EXAMPLES Hereinafter, although this invention is demonstrated further more concretely with reference to an Example, this invention is not intended to be limited to those Examples.

[Reactor]
FIG. 1 is a conceptual diagram of a reactor used in the present invention. In the figure, 1 is a nanobubble generator, and 3 is a flow controller, which controls the flow rate of an oxygen-containing gas (oxygen gas, air, etc.) supplied to the nanobubble generator 1. Reference numeral 5 denotes a reaction vessel in which a reaction solution 7 is accommodated. The reaction solution 7 is a solution of a raw material organic compound and optionally further contains a photosensitizer. A high pressure mercury lamp 9 (100 W) as a light source is attached to the reaction vessel 5 to irradiate the reaction solution 7 with light.

The nanobubble generator 1 and the reaction vessel 5 are connected by two pipes 11 and 12 whose one end is immersed in the reaction solution 7. The nanobubble generator 1, the pipe 11, the reaction vessel 5 and the pipe are connected to each other. 12, a circulation system is configured. The nanobubble generator 1 sucks the reaction solution 7 in the reaction vessel 5 through the pipe 12 and supplies oxygen (oxygen gas or air, etc., “Air / O ₂ ” in the figure) from the flow controller 3 at a predetermined flow rate. Is added to the reaction solution in the form of nanobubbles, discharged through the pipe 11, and returned to the reaction solution 7 in the reaction vessel 5. By the nanobubble generator 1 that is continuously operated during the reaction time, the reaction solution 7 in the reaction vessel 5 becomes a liquid in which nanobubbles containing oxygen are suspended in a concentrated manner. The reaction solution 7 in this state is irradiated with light from the high-pressure mercury lamp 9, and the raw organic compound is oxidized by singlet oxygen excited by light irradiation from the ground state to give a product.

  As the nanobubble generator 1, a micro / nanobubble generator MA3FS [Asp Co., Ltd.] was used. The nanobubble generator has a function of creating nanobubbles in a liquid by injecting a gas into the liquid, applying shearing force to the flow of the gas / liquid mixture with a static mixer, and repeating the division of the liquid.

[Measurement of bubble particle size]
The particle diameter of bubbles formed by the nanobubble generator was measured by a nanoparticle measuring device (NanoSight, Nippon Quantum Design Co., Ltd.). The measurement conditions were as follows.
・ Solvent: Ethyl acetate ・ Gas: Air ・ Nanobubble discharge pressure: 0 to 1.0 MPa
・ Liquid flow rate: 112 mL / min ・ Gas flow rate: 3 mL / min As a result of the measurement, the presence of bubbles was confirmed from the particle size of the smallest size of 3 nm that could be measured. The results are shown in FIG. In the figure, the horizontal axis is the bubble particle size, and the vertical axis is the number of bubbles with each particle size per mL of gas-liquid mixed fluid (in the figure, in the particle size range of about 50 nm or less, the graph is The number of bubbles cannot be determined because it is close to. The total number of bubbles formed (100%) has a particle size of 5 to 500 nm, and the bubbles with a particle size of 50 to 400 nm are well over 95% of the total number of bubbles. .

Example 1 Photo-oxygen oxidation of α-terpinene-1

It is known that the main product ascaridol (II) and the by-product p-cymene (III) are produced by photooxygen oxidation of α-terpinene (I). While introducing air into the reaction solution continuously in the form of nanobubbles as an oxygen source, photo-oxygen oxidation by irradiating the reaction solution with a high-pressure mercury lamp under normal pressure (1 atm) was attempted as follows. It was.
A photosensitizer (Rose Bengal or Methylene Blue) in an amount of 15 mol% with respect to the amount of α-terpinene is added to 50 mL of a 0.1M α-terpinene solution in methanol, and air is continuously introduced in the form of nanobubbles. However, it was subjected to the photooxygen oxidation reaction at a reaction solution temperature of 30 ° C. for the time shown in Table 1. For the light irradiation, an internal irradiation type photochemical reaction device UVL-100HA (manufactured by Riko Kagaku Sangyo Co., Ltd.) (water-cooled 100 W high-pressure mercury lamp) was used and the light source was immersed in the reaction solution for irradiation (internal irradiation).

The reaction solution after completion of the reaction was filtered through a short column (ethyl acetate, SiO ₂ : 1 g, Na ₂ SO ₄ : 10 mg), and the obtained solution was subjected to gas chromatography. The conversion rate of α-terpinene (consumption rate by reaction) and the respective proportions of ascaridol and p-cymene in the product were determined. The results are shown in Table 1.

  As shown in Table 1, when rose bengal or methylene blue was used as a photosensitizer at 15 mol% with respect to the raw material α-terpinene, the conversion rate of the raw material was 99 by reaction for 0.5 to 6 hours. The reaction was already substantially complete. The main product was alkali doll.

Example 2 Photooxidation of α-terpinene-2
As shown in Table 2, the concentration of α-terpinene as a raw material is set in the range of 0.1 to 0.025 M / methanol, and Rose Bengal as a photosensitizer is 1.0 or 3.0 relative to the raw material. The reaction was carried out while introducing air nanobubbles in the same manner as in Example 1 for 0.5 to 1 hour at a reaction solution temperature of 30 ° C. while being internally irradiated at normal pressure under normal pressure. After completion of the reaction, the conversion rate and the proportions of ascaridol and p-cymene in the product were determined in the same manner as in Example 1. The results are shown in Table 2.

  As can be seen from Table 2, even if the amount of rose bengal added as a photosensitizer is reduced to 1.0 or 3.0 mol% with respect to the raw material, the reaction temperature (30 ° C, reaction for 1 hour) .1 and No. 2) as well as the reaction for 0.5 hours (No. 3 and No. 4), the conversion rates of all raw materials exceeded 99%, and the reaction was already completed. Unexpectedly, p-cymene was obtained as the main product, and the amount of ascaridol produced was small.

Example 3 Photo-oxygen oxidation of γ-terpinene-1

  Production of p-cymene (III) by photooxygen oxidation of γ-terpinene (IV) was carried out under various conditions under normal pressure. After the reaction, the product was subjected to gas chromatography in the same manner as in Example 1 to determine the conversion rate of γ-terpinene. The reaction conditions and results are shown in Table 3. In the gas introduction column of Table 3, “BAB (air)” means that air is simply blown into the reaction solution (not in the form of nanobubbles), and “BAL (air)” The balloon contained in is connected to the reaction vessel, and air is supplied to the gas phase side in the reaction vessel.

  As can be seen from Table 3, methanol was used as a solvent, rose bengal (RB) as a photosensitizer, air was introduced by normal bubbling instead of nanobubbles, and No. 4 using a balloon, 2 hours. After the reaction, the raw material conversions were as low as 34% and 4%, respectively. On the other hand, in the case of using nanobubbles, even No. 14 to which no photosensitizer was added showed a conversion rate of 49%.

  All the reactions (No. 1, 2, 5, and 10) that used nanobubbles, the photosensitizer as rose bengal, and the solvent as methanol (No. 1, 2, 5, and 10) were already completed in 1 to 2 hours (conversion) Rate> 99%). When compared with those using rose bengal as a photosensitizer, methanol, THF / methanol (5/1), and isopropanol / methanol (5/1) are equally superior among the solvents used (all converted) Rate> 99%), indicating that methanol, isopropanol and THF can be used as equally good solvents. However, even when ethyl acetate / methanol (5/1) or acetonitrile / methanol (5/1) is used as the solvent, a conversion rate of 75% is obtained, so these solvents can also be used. It becomes a solvent candidate in the case where the photo-oxygen oxidation reaction is carried out with a raw material that is difficult to perform.

  In any case where nanobubbles are used, those using 5,10,15,20-tetraphenylporphine (TPP) as photosensitizers other than rose bengal (No. 12), the raw material is reacted in 2 hours. The conversion was 75%, 65% for methylene blue (MB) (No. 11) and 62% for p-benzoquinone (No. 13). From this, it is clear that Rose Bengal is particularly superior among these photosensitizers in the photooxygen oxidation reaction under the introduction of air (or oxygen) by nanobubbles. However, other photosensitizers can also be advantageously used in the photo-oxygen oxidation reaction under the introduction of nanobubbles because they show a higher raw material conversion than the result of No. 14 in which no photosensitizer is used.

[Example 4] Production of imine by dehydrogenation of primary amine and homocoupling-1

A formula Z—CH ₂ —NH ₂ in which a methylene group is bonded to a nitrogen atom [Z represents an arbitrary group. As an example of the primary amine, the above amine (V) is selected, and air or oxygen is supplied in the form of nanobubbles under normal pressure at a reaction solution temperature of 30 ° C. in the same manner as in Examples 1-2. A photo-oxygen oxidation reaction was performed below, and the conversion rate of raw materials or the yield of imine (VI) was examined. Rose Bengal or TPP was used as a photosensitizer. In addition, decane (10 μM) was added to the reaction solution, and benzylamine as a raw material was quantified using this as an internal standard substance in gas chromatography. The reaction conditions and results are shown in Table 4 below.

  As seen in Table 4, rose bengal was used as a photosensitizer at a concentration of only 0.1 mol% based on the raw material, and the reaction rate was 30 hours at a reaction solution temperature of 0.3 hours (18 minutes). % Was achieved (No. 2). Furthermore, at a lower 0.01 mol% use, a conversion rate of 99% was achieved in 1 hour (No. 3). Furthermore, when 0.001 mol%, which is an order of magnitude lower, was used, the conversion rate reached 70% in 4 hours (No. 5), which was 74% with no photosensitizer added (No. 6, 7). % And 47% are not considered to be substantially different. Rather, this shows that the photo-oxygen oxidation performed while introducing air (or oxygen) in the form of nanobubbles substantially proceeds with the oxidation reaction without adding a photosensitizer.

  In addition, when the photosensitizer is TPP, an imine yield of 99% was achieved in 4 hours even when a very small amount of 0.001 mol% was used with respect to the raw material (No. 12).

[Example 5] Production of imine by dehydrogenation of primary amine and homocoupling-2

  Photooxygen oxidation was attempted in the same manner as in Example 4 using benzylamine having a methyl group, methoxy group, chloro group, or trifluoromethyl group on the phenyl group as a raw material instead of the benzylamine used as a raw material in Example 4. . For comparison, at the same time, the same reaction was attempted by normal bubbling (BAB) instead of nanobubbles (NB). The raw material compounds, reaction conditions and results are shown in Table 5 below.

  As can be seen in Table 5, in any benzylamine having any substituent, the photo-oxygen oxidation performed while introducing air in the form of nanobubbles showed a much higher conversion rate than that obtained by normal bubbling. .

Example 6 Production of imine by dehydrogenation of secondary amine

  1. Imine (XII) conversion of N-benzylpropan-2-amine (XI)

N-benzylpropan-2-amine (XI) in which R ^a is a phenyl group and R ^b is an isopropyl group in the formula (IX) is used as a raw material, and TPP is used as a photosensitizer using 0.02 mol% of the raw material. In a acetonitrile solution containing 20 μM of decane, a photo-oxygen oxidation reaction was carried out by irradiating with light while introducing nanobubbles (air) in the same manner as in the above examples for 1 hour at a reaction solution temperature of 30 ° C. As a result, the corresponding imine (XII) was obtained with a yield of 80%. When the photo-oxygen oxidation reaction was carried out for 1 hour while introducing air by normal bubbling under the same conditions, the yield of imine (XII) was 29%.

  2. Conversion of tetrahydroisoquinoline (XIII) to imine (XIV)

Using 1,2,3,4-tetrahydroisoquinoline (XIII) in which R ^a is a phenyl group and R ^b is an ethylene group substituted at the second position of the phenyl group in the formula (IX), In the same manner, however, the photooxygen oxidation reaction was carried out for 1.5 hours, and the corresponding 3,4-dihydroisoquinoline (XIV) was obtained in a yield of 88%. When the other conditions were the same and the photooxygen oxidation reaction was carried out for 1.5 hours by normal bubbling, the yield of imine (XIV) was 50%.

  3. Conversion of dibenzylamine (XV) to imine (XVI)

Dibenzylamine (XV), in which R ^a is a phenyl group and R ^b is a benzyl group in the formula (IX), is reacted for 1 hour in the same manner as in 1 above, and the yield of imine (XVI) is 99%. Was obtained. When the other conditions were the same and the photooxygen oxidation reaction was carried out for 1 hour by normal bubbling, the yield of imine (XVI) was only 23%.

Example 7 Selective Production of Sulfoxide by Photooxygen Oxidation of Sulfide Selective production of methylsulfinylbenzene by photooxygen oxidation of thioanisole-1

The raw material thioanisole (XVII) was dissolved in acetonitrile / methanol (5/1) at a concentration of 0.1 M, no photosensitizer was used, decane 10 mM was added as an internal standard, The reaction was carried out while introducing air in the form of nanobubbles for 3 hours at a reaction solution temperature of 30 ° C. while irradiating. As a result, the conversion rate of the raw material was 99%, and the yield of sulfoxide (XVIII) was 78%. The ratio of sulfoxide / sulfone (Ph-SO ₂ -Me) was 99/1 (area ratio in gas chromatography), and the reaction was almost completely sulfoxide selective with these two products.

2. Selective production of methylsulfinylbenzene by photooxygen oxidation of thioanisole-2
Following the above, we tried to produce methylsulfinylbenzene by photooxidation by internal irradiation while introducing air in the form of nanobubbles by changing the type of solvent, photosensitizer, amount and presence, and reaction time. . The conditions and results are shown in Table 6 below.

As can be seen in Table 6, the reaction proceeded well even without photosensitizer. Moreover, irrespective of the presence or absence of a photosensitizer, the R ₂ SO / R ₂ SO ₂ ratio (sulfoxide / sulfone ratio) was 97/3 to 100/0, and the reaction was highly sulfoxide-selective. The conversion rate of the raw material was particularly high when methanol, acetonitrile, or a mixture of these was used.

  3. Selective production of sulfoxides by photooxygenation of various sulfides.

  In 1 and 2 above, it is confirmed that when nanobubbles are used in the photooxygen oxidation of thioanisole, highly selective oxidation from sulfide to sulfoxide occurs and the reaction proceeds well even without the use of a photosensitizer. Therefore, other sulfides were examined. That is, each raw material compound in Table 7 was dissolved in acetonitrile / methanol (5/1) at a concentration of 0.1 M, decane 10 mM was added as an internal standard, and 30 ° C. in the presence or absence of a photosensitizer. Then, photo-oxygen oxidation was attempted by internal irradiation while supplying air with nanobubbles or normal bubbling. The results are also shown in Table 7.

As can be seen in the table, the reaction proceeds without photosensitizer, and the photo-oxygen oxidation under the introduction of air (or oxygen) by nanobubbles (NB) is significantly more difficult than the reaction under the introduction of air by bubbling. High conversion and sulfoxide yield were obtained. In addition, the comparison between the conversion rate and the sulfoxide yield and the comparison with the results shown in Table 6 indicate that highly selective sulfoxide oxidation occurs for these various sulfides in the photooxygen oxidation using nanobubbles. This selectivity is not affected by whether the group bonded to the nitrogen atom, R ^c and R ^d is aromatic or aliphatic. This indicates that the highly selective oxidation of sulfides to sulfoxides by photooxygen oxidation using nanobubbles can be applied to a wide variety of sulfides in general.

  The present invention drastically improves the reaction efficiency of the photooxygen oxidation reaction, reduces or eliminates the use of photosensitizer, selective photooxygen oxidation of sulfide to sulfoxide, and adjustment of the amount of photosensitizer. This is useful in opening up the possibility of selecting things.

1: Nanobubble generator 3: Flow controller 5: Reaction vessel 7: Reaction solution 9: High-pressure mercury lamp 11, 12: Pipe

Claims (10)

An improved production method for producing a product by photo-oxygen oxidation of a raw organic compound, wherein an oxygen-containing gas is injected into the raw organic compound-containing solution under light irradiation in the form of nanobubbles, The production method is characterized in that the product is obtained by maintaining a state in which the nanobubbles of the oxygen-containing gas are dispersed in a solution to advance a photo-oxygen oxidation reaction of the raw organic compound,
The starting organic compound is α-terpinene, γ-terpinene, R ¹ CH ₂ NH ₂ [wherein R ¹ represents an aromatic group which may have a substituent. ], R ¹ CH ₂ NHR ² [wherein, R ¹ is as defined above, and R ² is a saturated hydrocarbon group which may have a substituent or an aromatic group which may have a substituent. Represents. And one selected from the group consisting of sulfides,
The nanobubbles are those having 90% or more of bubbles having a particle diameter of 5 nm or more and less than 1000 nm,
The concentration of the photosensitizer in the solution is
When the starting organic compound is α-terpinene, γ-terpinene or sulfide, it is 3 mol% or less based on this,
When the raw organic compound is R ¹ CH ₂ NH ₂ or R ¹ CH ₂ NHR ^2, it is 0.1 mol% or less based on this,
And optical sensitizer, Ri Rose Bengal, methylene blue, and 5,10,15,20 der those selected from the group consisting of tetraphenyl porphine,
The raw organic compound (M) and the product (P) have the following combinations:
(i) M: α-terpinene, P: p-cymene
(ii) M: R ¹ CH ₂ NH ₂ , P: R ¹ CH═NCH ₂ R ¹
[Wherein, R ¹ represents an aromatic group which may have a substituent. ]
(iii) M: R ¹ CH ₂ NHR ² , P: R ¹ CH═NHR ²
[ Wherein , R ¹ is as defined above, and R ² represents a saturated hydrocarbon group which may have a substituent or an aromatic group which may have a substituent. ]
(iv) M: sulfide, P: sulfoxide
A manufacturing method that is more selected .
Production method.   The manufacturing method according to claim 1, wherein the light source for light irradiation is selected from a mercury lamp, a halogen lamp, an LED lamp, and an incandescent lamp. The production method according to claim 1 or 2 , wherein the aromatic ring portion of R ¹ has 6 to 10 carbon atoms. The substituent of R ¹ is selected from the group consisting of R ³ —, R ³ O— and X, where R ³ may be substituted with one or more halogen or hydroxyl groups. 2. A saturated hydrocarbon group having 1 to 6 carbon atoms, or a phenyl group which may be substituted with one or more halogens or hydroxyl groups, and X represents a halogen. The manufacturing method in any one of -3 . R ² represents a saturated hydrocarbon group having 1 to 10 carbon atoms which may have a substituent, or an aromatic group having 6 to 10 carbon atoms which may have a substituent, or R ² represents R ¹ combine with those representing the formed optionally may saturated hydrocarbon group a ring, either method according to claim 1-4. The substituent of R ² is selected from the group consisting of R ⁴ —, RO—, and X, where R ⁴ is the number of carbon atoms that may be substituted with one or more halogen or hydroxyl groups. represent a 1-6 saturated hydrocarbon group, or one or two or more halogens which may be substituted phenyl, X is intended to represent a halogen or a hydroxyl group, according to claim 1 to 5 Any manufacturing method of. The starting organic compound (M) and the product (P) may have (M) 1,2,3,4-tetrahydroisoquinoline which may have a substituent and (P) substituent 3, The production method according to any one of claims 1 to 6 , which is 4-dihydroisoquinoline. The sulfide and sulfoxide are R ⁶ —S—R ⁷ and R ⁶ —SO—R ⁷ , respectively, wherein R ⁶ and R ⁷ are the same or different and may have a substituent. Or represents an optionally substituted aromatic group]. The production method according to any one of claims 1 to 7 The method according to claim 8 , wherein the saturated hydrocarbon group has 1 to 10 carbon atoms, and the aromatic ring portion of the aromatic group has 6 to 10 carbon atoms. The substituent of R ⁶ or R ⁷ represents R ⁸ —, R ⁸ O— or X, and R ⁸ has 1 to 6 carbon atoms which may be substituted with one or more halogen or hydroxyl groups; The production method according to claim 9 , which represents an alkyl group, and X represents a halogen or a hydroxyl group.

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