A diamine-substituted hypocrellin derivative and its preparation method and application

Abstract

The present invention discloses a cyclohexanediamine-substituted hypocrellin derivative shown in formula (I), a synthesis method and application thereof. The hypocrellin derivative prepared by the present invention has strong continuous absorption in the visible light region of 400-700nm, with a maximum absorption wavelength of 640nm and a corresponding molar extinction coefficient of 36000nm. ‑1 cm ‑1 , showing strong visible light absorption ability; the hypocrellin derivative can efficiently produce singlet oxygen (active oxygen efficiency is as high as 0.45), and has good light stability and pH stability, and can be used as a photosensitizer for the photooxidative synthesis of 2,3,5-trimethylbenzoquinone. By optimizing different reaction conditions, such as substrate concentration, different solvents, photosensitizer concentration, reaction time, reaction temperature, etc., the target product 2,3,5-trimethylbenzoquinone was synthesized with high yield and high selectivity. #imgabs0#

Description

[0001] The present invention claims priority to a prior application entitled “A diamine-substituted hypocrellin derivative, preparation method and application thereof”, with patent application number 202110741437.0, filed with the State Intellectual Property Office of China on June 30, 2021. The entire text of the prior application is incorporated herein by reference. Technical Field

[0002] The invention relates to the technical field of photo-oxidative synthesis of hypocrellin, and more specifically to a diamine-substituted hypocrellin derivative used for photo-oxidative synthesis of 2,3,5-trimethylbenzoquinone. Background Art

[0003] Vitamin E is an important antioxidant and is widely used in the fields of medicine, cosmetics, food, and health products. Vitamin E is of great significance for maintaining the balance of the redox environment in the human body. When the human body lacks vitamin E, the free radicals of the metabolites in the body can cause lipid peroxidation in the biological membrane, destroy the structure and function of the cell membrane, and form lipofuscin; the lack of vitamin E can also cause protein denaturation, enzyme and hormone inactivation, decreased immunity, metabolic disorders, and promote aging and hemolysis. Although many plants (such as vegetable oil, kiwi, spinach, cabbage, kale, lettuce, sweet potato, yam, citrus peel, etc.) are rich in vitamin E, the domestic and foreign markets have a huge demand for vitamin E. Vitamins extracted from natural products cannot meet the increasing demand for life. People seek to prepare vitamin E by chemical synthesis. 2,3,5-Trimethylbenzoquinone (TMBQ) is an important intermediate of vitamin E. After hydrogenation, 2,3,5-trimethylhydroquinone is obtained, which is then condensed with isophytol and esterified to obtain vitamin E acetate. Therefore, 2,3,5-trimethylbenzoquinone is the most important raw material for synthesizing vitamin E.

[0004] 2,3,5-Trimethylbenzoquinone is mainly obtained by oxidation of 2,3,5-trimethylphenol, and the oxidant used is usually K2Cr2O3, RuC13, MnO2, H2O2 or concentrated sulfuric acid. This method uses toxic oxidants during the reaction and produces a large amount of industrial waste liquid and waste residue, which will cause certain environmental pollution. In addition to oxidation with oxidants, copper halide can also be used as a catalyst for catalytic oxidation, but its yield is relatively low and it is also prone to catalyst deactivation and environmental pollution.

[0005] In recent years, people have tried to synthesize 2,3,5-trimethylbenzoquinone by photosensitive oxidation. The photosensitive oxidation method is to introduce a catalytic amount of photosensitizer into the system. Under light excitation, the photosensitizer produces a triplet excited state and produces singlet oxygen through energy transfer. The singlet oxygen produced has strong oxidizing properties and can efficiently oxidize 2,3,5-trimethylphenol to 2,3,5-trimethylbenzoquinone. In the above photooxidation reaction, photosensitizer, light source and oxygen are the three elements of photosensitive oxidation. Compared with traditional oxidation, the photosensitive oxidation method has the advantages of cleanliness and high efficiency, and has broad application prospects. The singlet oxygen in the reaction is directly generated by the photosensitizer sensitizing oxygen, and oxidizes with the raw material to generate the target product, and avoids the use of toxic oxidants in the reaction. Photosensitizer is the key to the photooxidation reaction, and the efficiency of substrate oxidation mainly depends on the efficiency of the photosensitizer in generating reactive oxygen. For example, Murtinho et al. synthesized porphyrin photosensitizers for photooxidation of phenolic compounds. Studies have shown that the singlet oxygen generation efficiency of porphyrin derivatives with different substituents varies greatly. The oxidation yield of most photosensitizers is less than 50%, and only a few photosensitizers with heavy atom effects modified by halogen elements can achieve an oxidation yield of 70%. In addition, dyes such as methylene blue and rose bengal are also often used as photosensitizers to participate in photosensitive oxidation reactions. For example, Griffiths used methylene blue to catalyze the oxidation of 1,5-dihydroxynaphthalene to synthesize juglone, obtaining a yield of more than 70%. Therefore, photosensitive oxidation is an effective method for the oxidation of phenol. 2,3,5-Trimethylphenol and juglone have similar structures and belong to the oxidation of phenol, so they should also be oxidized with photosensitizers. However, the above-mentioned porphyrin photosensitizers have problems such as weak absorption in the visible light window and low singlet oxygen efficiency, and their photooxidation yields are generally not high (30-60%). Therefore, it is still necessary to find new photosensitizers to oxidize and produce 2,3,5-trimethylbenzoquinone.

[0006] Hypocrellin is a natural plant photosensitizer, belonging to the perylenequinone class of compounds, produced by a parasitic fungus (hypocrellin) on the arrow bamboo above 3000 meters above sea level on the Yunnan Plateau in my country. Natural hypocrellin mainly exists as hypocrellin A (HA) and hypocrellin B (HB). Hypocrellin has strong absorption in the visible light region and a large molar extinction coefficient, and can efficiently produce singlet oxygen under photosensitivity conditions, and can be used for photocatalytic oxidation reactions. However, the maximum absorption wavelength of natural hypocrellin is 460nm, and the absorption is weak in the red light region with a longer wavelength. In order to improve its photooxidation efficiency, it is necessary to broaden its absorption wavelength and increase its singlet oxygen yield through reasonable structural modification. Therefore, it is necessary to develop new structurally modified hypocrellin derivatives so that the photosensitizer has a stronger light absorption ability in the visible light region. Summary of the invention

[0007] In order to improve the above technical problems, the present invention provides a compound represented by formula (I), or its enol tautomer formula (I'):

[0008]

[0009] wherein A is absent or is selected from a 5-7 membered cycloalkane fused to an adjacent piperazine ring;

[0010] R is selected from -COCH3 or -H.

[0011] According to an embodiment of the present invention, A is absent or is selected from cyclohexane, cyclopentane, cycloheptane fused to the adjacent piperazine ring.

[0012] According to an embodiment of the present invention, the compound represented by formula (I) has a structure represented by formula (I-1) or (I-2), and its enol tautomer formula (I') has a structure represented by formula (I-1') or (I-2'):

[0013]

[0014] wherein A and R have the definitions given above.

[0015] According to an embodiment of the present invention, the compound represented by formula (I) is selected from the cyclohexanediamine-substituted hypocrellin derivative CHA-HC and its enol tautomer CHA-HC', and its molecular structure is shown in the following formula:

[0016]

[0017] According to an embodiment of the present invention, the compound represented by formula (I) is selected from the group consisting of ethylenediamine-substituted hypocrellin derivatives EDA-HB and their enol tautomers EDA-HB', and their molecular structures are shown in the following formula:

[0018]

[0019] The present invention also provides a method for preparing a compound of formula (I), comprising: reacting a compound of formula (II) with compound 2 to obtain a compound of formula (I);

[0020]

[0021] Wherein, A and R have the definitions given above;

[0022] According to an embodiment of the present invention, the reaction temperature is 40-120°C, for example, 50-100°C, exemplified by 60°C, 80°C;

[0023] According to an embodiment of the present invention, the reaction time is 6 to 48 hours, for example, 12 to 42 hours, and exemplarily 36 hours;

[0024] According to an embodiment of the present invention, the reaction can be carried out in a solvent, and the solvent is an organic solvent, or a mixed solvent of an organic solvent and water. The mass fraction of water in the mixed solvent of organic solvent and water is 5wt% to 95wt%; the organic solvent is one or more of acetonitrile, tetrahydrofuran, pyridine, N,N-dimethylformamide, dimethyl sulfoxide, methanol or ethanol. More preferably, the organic solvent is tetrahydrofuran or acetonitrile.

[0025] According to an embodiment of the present invention, the preparation method of the compound of formula (I) wherein R is H (i.e., formula (I-1)) may comprise the following steps:

[0026]

[0027] Wherein, A has the definition given above;

[0028] 1) Compound HB reacts with an alkaline aqueous solution to obtain compound HC;

[0029] 2) Compound HC reacts with compound 2 to obtain a compound represented by formula (I-1).

[0030] According to an embodiment of the present invention, in step 1), the alkali may be sodium hydroxide, lithium hydroxide, potassium hydroxide, potassium carbonate, or cesium carbonate; the mass concentration of the alkaline aqueous solution may be 0.5 to 5%, for example, 0.8 to 3%, and exemplarily 3.0%;

[0031] According to an embodiment of the present invention, in step 1), the reaction temperature is 60 to 150° C., for example, 80 to 120° C., and exemplarily 100° C. The reaction time can be 2 to 24 hours, for example, 6 to 12 hours, and exemplarily 8 hours;

[0032] The present invention also provides the use of the compound represented by formula (I) as a photosensitizer, for example, in the preparation of 2,3,5-trimethylbenzoquinone.

[0033] The present invention also provides a method for preparing 2,3,5-trimethylbenzoquinone, which comprises using the compound represented by formula (I) as a photosensitizer.

[0034] According to an embodiment of the present invention, the preparation method comprises: mixing 2,3,5-trimethylphenol with a compound represented by formula (I), and reacting them under light and an oxygen-containing atmosphere to obtain 2,3,5-trimethylbenzoquinone.

[0035] The preparation method specifically comprises the following steps: dissolving 2,3,5-trimethylphenol and a compound represented by formula (I) in a mixed solution of ethanol and water to obtain a reaction solution, transferring the reaction solution to a photochemical reactor, continuously introducing oxygen into the photochemical reaction container, irradiating the reaction solution with a light source and continuously stirring to react, thereby obtaining the product 2,3,5-trimethylbenzoquinone.

[0036] According to an embodiment of the present invention, the light source is preferably 50 mW / cm 2 White LED light source;

[0037] According to an embodiment of the present invention, the concentration of 2,3,5-trimethylphenol in the reaction solution is 0.1 to 100 mmol / L. More preferably, the concentration of 2,3,5-trimethylphenol in the reaction solution is 10 mmol / L.

[0038] According to an embodiment of the present invention, the volume ratio of ethanol to water is 1 to 10: 1. More preferably, the volume ratio of ethanol to water is 4:1.

[0039] According to an embodiment of the present invention, the concentration of the compound represented by formula (I) is 0.001 to 1.00 mmol / L. More preferably, the concentration of the compound represented by formula (I) in the reaction solution is 0.10 mmol / L.

[0040] According to an embodiment of the present invention, the reaction temperature is 10 to 40° C., preferably 30° C. The reaction time is preferably 2 to 12 hours.

[0041] According to an embodiment of the present invention, the photochemical reactor is a transparent quartz reactor with an interlayer, reflux water is introduced into the interlayer, and the reaction temperature is controlled by controlling the water temperature.

[0042] Beneficial Effects

[0043] The present invention discloses a hypocrellin derivative represented by formula (I), a synthesis method thereof, and an application thereof in the photooxidation of 2,3,5-trimethylphenol. The compound represented by formula (I) prepared by the present invention, such as CHA-HC or EDA-HB, has strong continuous absorption in the visible light region of 400 to 700 nm, with a maximum absorption wavelength of 640 nm and a corresponding molar extinction coefficient of 36000 nm. -1 cm -1, showing strong visible light absorption ability; CHA-HC or EDA-HB can efficiently produce singlet oxygen (active oxygen efficiency is as high as 0.45), and has good light stability and pH stability, and can be used as a photosensitizer for 2,3,5-trimethylbenzoquinone photooxidation synthesis. The present invention uses a white light LED light source to replace the high-pressure mercury lamp light source of the ordinary photooxidation process, which greatly reduces the by-products of the reaction and saves energy; replaces the conventional organic solvent with an environmentally friendly mixture of ethanol and water; utilizes the white light LED light source and the absorption spectrum of the bamboo red fungus photosensitizer CHA-HC or EDA-HB to have good overlapping matching characteristics, and the photooxidation can obtain 85% of 2,3,5-trimethylbenzoquinone yield, which not only greatly saves the cost of the reaction, but also makes the product easy to separate and purify. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 :Comparison of absorption spectra of commercial porphyrin photosensitizer PpIX, hypocrellin B HB, CHA-HC and EDA-HB

[0045] Figure 2 :(a) Photodegradation curves of DHPA by hypocrellin derivatives CHA-HC and EDA-HB; (b) Comparison of photodegradation of DHPA by CHA-HC, EDA-HB and RB

[0046] Figure 3 :(a) CHA-HC, EDA-HB and commercial photosensitizer HpD at 50 mW / cm 2 (a) Comparison of the photostability of CHA-HC, EDA-HB and commercial hematoporphyrin HpD after irradiation with a white light LED for 30 min; (b) Comparison of the pH stability of CHA-HC, EDA-HB and commercial hematoporphyrin HpD DETAILED DESCRIPTION

[0047] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0048] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0049] Example 1

[0050]

[0051] Preparation of HB: 1.2 g of HA was dissolved in 1 L of 1.5% KOH aqueous solution, stirred and reacted for 12 hours in a dark place, and the reaction solution was neutralized with dilute hydrochloric acid. A large amount of red solid product precipitated, which was filtered, washed with distilled water several times and dried to obtain HB with a yield of 95%.

[0052] Preparation of deacetylhypocrellin (HC): 1 g of hypocrellin B was dissolved in 500 mL of 3% KOH aqueous solution, protected from light and refluxed for 6 h, and then cooled and neutralized with dilute hydrochloric acid to pH = 4. The product was extracted with dichloromethane, separated and purified to obtain deacetylhypocrellin B (HC), with a yield of 65%. MS (ESI+): 487.8. 1 H NMR(CDCl3,δ,ppm):16.2(s,-OH,1H),15.9(s,-OH,1H),6.63(d,1H),6.35(s,2H ),4.14,4.11(s,-OCH3,6H),4.02(s,-OCH3,3H),3.1(d,2H),2.24(s,-OCH3,3H).

[0053] Example 2

[0054]

[0055] Preparation of the CHA-HC derivative of CHA: Dissolve deacetyl CHA-HC (1 mmol) and cyclohexanediamine (20 mmol) in 50 mL of tetrahydrofuran solvent, mix thoroughly, heat to reflux under nitrogen protection, and stir to react for 24 hours in the dark. After the reaction is completed, remove the solvent by rotary evaporation. The blue-black solid residue is dissolved in 200 mL of dichloromethane, washed three times with 100 mL of dilute hydrochloric acid solution and three times with distilled water, and the organic layer is dried with anhydrous magnesium sulfate, filtered, and the organic phase is rotary dried to obtain a crude product. The obtained crude product is further separated by silica gel plate chromatography, and the developing solvent is dichloromethane: ethyl acetate (volume ratio of 4:1), to obtain a blue-black solid product, R f The values ​​were 0.45, and the yield was 26.5%. MS (ESI+): 550.28. 1H NMR(CDCl3,δ,ppm):16.82(s,-OH,1H),11.88(s,-NH,1H),6.40(s,Ar,1H),6 .33(s,Ar,1H),5.97(s,Ar,1H),4.08(s,-OCH3,3H),4.01(s,-OCH3,3H),3.95 (s,-OCH3,3H),3.33-3.23(d,-CH2-,2H),3.13-3.05(s,-CH2-,2H),2.23(s, -CH3,3H),2.11(s,-CH2-,2H),1.92(s,-CH2-,2H),1.52-1.50(s,-CH2-,4H).

[0056] Example 3

[0057]

[0058] Preparation of EDA-HB derivatives: EDA-HB (1 mmol) and ethylenediamine (5 mmol) were dissolved in 50 mL of tetrahydrofuran solvent, mixed thoroughly, heated to reflux under nitrogen protection, and stirred in the dark for 36 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The blue-black solid residue was dissolved in 200 mL of dichloromethane, washed three times with 100 mL of dilute hydrochloric acid solution and three times with distilled water, and the organic layer was dried with anhydrous magnesium sulfate, filtered, and the organic phase was dried to obtain a crude product. The crude product was further separated by silica gel plate chromatography, and the developing solvent was dichloromethane: ethyl acetate (volume ratio of 3:1) to obtain a blue-black solid product, R f The values ​​were 0.40, and the yield was 25%. MS (ESI+): 538.19.

[0059] The absorption spectra of CHA-HC and EDA-HB synthesized by the present invention are shown in FIG. Figure 1 shown. Figure 1 The absorption spectra of CHA-HC, EDA-HB, HB and PpIX are shown. The commercial porphyrin photosensitizer PpIX has multi-band absorption, all of which are narrow absorption bands, with maximum absorption wavelengths of 450, 480, 520 and 570 nm, respectively, and their molar extinction coefficients are all lower than 10000 M -1 cm -1; Therefore, the light absorption capacity of commercial PpIX in the visible light window is limited. The absorption spectrum properties of the bamboo red fungus and its derivatives disclosed in the present invention are completely different from them. The maximum absorption peak of HB is around 460nm. The CHA-HC and EDA-HB prepared by the present invention have very strong absorption in the visible light region. They have a wide continuous absorption band between 400 and 700nm, and the maximum absorption peaks are located at around 470 and 640nm, respectively, which is about 170nm red-shifted than the maximum absorption peak of HB, and the molar extinction coefficient is about 36000M -1 cm -1 , showing extremely strong visible light absorption ability.

[0060] The singlet oxygen efficiency of the CHA-HC and EDA-HB synthesized in the present invention in the solution is determined by the DHPA method. Figure 2 (a) is the photodegradation curve of DHPA by CHA-HC under light conditions. It can be seen that the photosensitizer CHA-HC obviously produces singlet oxygen under light conditions, thereby significantly degrading DHPA. By comparing and calculating the singlet oxygen efficiency curve of the reference material Rose Bengal RB ( Figure 2 (b)), the singlet oxygen efficiency of CHA-HC is 0.45, and the singlet oxygen efficiency of EDA-HB is 0.42, showing a strong ability to produce reactive oxygen species and can be used for photooxidation catalytic reactions.

[0061] Comparison of the photostability of CHA-HC, EDA-HB prepared by the present invention and commercial photosensitizers Figure 3 As shown. Figure 3 As can be seen in (a), the white light LED light source at 50mW / cm 2 After irradiation for 30 minutes at 50 mW / cm2, the absorption spectra of CHA-HC and EDA-HB did not decrease significantly, and the absorption intensity of the maximum wavelength decreased by less than 5%. 2 After 30 minutes of illumination at a low light intensity, the absorption spectrum of the commercial hematoporphyrin photosensitizer HpD decreased by about 50%. Therefore, CHA-HC and EDA-HB have better photostability than commercial photosensitizers.

[0062] The pH stability of CHA-HC and EDA-HB prepared by the present invention is as follows: Figure 3(b) As shown. The absorption spectra of CHA-HC and EDA-HB do not change significantly when the pH value is in the range of 6.2 to 8.0, indicating that CHA-HC and EDA-HB have good pH stability under physiological conditions; while the commercial hematoporphyrin HpD contains two carboxyl groups, which can be deprotonated in the pH range of 6.2 to 8.0, resulting in a significant change in the absorption spectrum, thus showing the instability of the HpD photosensitizer. Therefore, CHA-HC and EDA-HB have better pH stability than the commercial hematoporphyrin HpD in the pH range of 6.2 to 8.0.

[0063] It can be seen that CHA-HC and EDA-HB have strong continuous absorption in the visible light region of 400-700nm, and the molar extinction coefficient of the maximum wavelength is 36000M -1 cm -1 , showing extremely strong visible light absorption ability; CHA-HC and EDA-HB can efficiently produce singlet oxygen, and have good light stability and pH stability, and can be used as photosensitizers in the photocatalytic oxidation reaction of phenols.

[0064] Example 4

[0065] At 50mW / cm 2 Under the irradiation of white LED light, different concentrations of 2,3,5-trimethylphenol (substrate concentrations were 0.1, 1, 5, 8, 10, 50, 100 mM) were dissolved in 50 mL of ethanol and water (volume ratio 4:1) mixed solvent, and the bamboo red fungus derivative CHA-HC or EDA-HB was added as a photosensitizer (concentration was 0.10 mM), and oxygen was continuously introduced into the transparent quartz reaction container. The reaction was stirred at room temperature (30°C) for 8 hours. The solvent was removed by vacuum distillation, and the crude product was separated by column chromatography (petroleum ether / ethyl acetate, 5:1, v / v) to obtain 2,3,5-trimethylbenzoquinone. The reaction yields are shown in Tables 1 and 2. MS (ESI+): 150.18. 1 H NMR (CDCl3, δ, ppm): 6.58 (s, 1H), 2.02 (s, -CH3, 9H).

[0066] Table 1: Effect of substrate concentration on the photooxidation yield of 2,3,5-trimethylphenol (CHA-HC)

[0067]

[0068] Table 2: Effect of substrate concentration on the yield of 2,3,5-trimethylphenol photooxidation reaction (EDA-HB)

[0069]

[0070] Example 5

[0071] At 50mW / cm 2 Under the irradiation of white LED light, the raw material 2,3,5-trimethylphenol (substrate concentration is 10mM) is dissolved in 50mL of ethanol and water (volume ratios are 1:1, 2:1, 4:1, 6:1, 8:1, 10:1) mixed solvent, oxygen is continuously introduced into the transparent quartz reaction container, and the bamboo red fungus derivative CHA-HC or EDA-HB is added as a photosensitizer (concentration is 0.10mM), and the reaction is stirred at room temperature (30℃) for 8h. The solvent is removed by vacuum distillation, and the crude product is separated by column chromatography (petroleum ether / ethyl acetate, 5:1, v / v) to obtain 2,3,5-trimethylbenzoquinone, and the reaction yield is shown in Table 3.

[0072] Table 3: Effect of solvent on the yield of 2,3,5-trimethylphenol photooxidation reaction (CHA-HC)

[0073]

[0074] Example 6

[0075] At 50mW / cm 2 Under the irradiation of white LED light, the raw material 2,3,5-trimethylphenol (substrate concentration is 10mM) was dissolved in 50mL of ethanol and water (volume ratio is 4:1) mixed solvent, and different amounts of hypocrellin derivatives CHA-HC or EDA-HB were added as photosensitizers (concentrations were 0.001, 0.01, 0.05, 0.08, 0.10, 0.50, 1.00mM, respectively). Oxygen was continuously introduced into the transparent quartz reaction container, and the reaction was stirred at room temperature (30°C) for 8h. The solvent was removed by vacuum distillation, and the crude product was separated by column chromatography (petroleum ether / ethyl acetate, 5:1, v / v) to obtain 2,3,5-trimethylbenzoquinone. The reaction yields are shown in Tables 4 and 5.

[0076] Table 4: Effect of photosensitizer concentration on the yield of 2,3,5-trimethylphenol photooxidation reaction (CHA-HC)

[0077]

[0078]

[0079] Table 5: Effect of photosensitizer concentration on the yield of 2,3,5-trimethylphenol photooxidation reaction (EDA-HB)

[0080]

[0081] Example 7

[0082] At 50mW / cm 2Under the irradiation of white LED light, the raw material 2,3,5-trimethylphenol (substrate concentration is 10mM) is dissolved in 50mL of ethanol and water (volume ratio is 4:1) mixed solvent, and the bamboo red fungus derivative CHA-HC or EDA-HB is added as a photosensitizer (concentration is 0.10mM), and oxygen is continuously introduced into the transparent quartz reaction container. The reaction is stirred for 8h under different reaction temperature conditions (10, 20, 30, 40℃). The solvent is removed by vacuum distillation, and the crude product is separated by column chromatography (petroleum ether / ethyl acetate, 5:1, v / v) to obtain 2,3,5-trimethylbenzoquinone, and the reaction yield is shown in Table 6.

[0083] Table 6: Effect of reaction temperature on the yield of 2,3,5-trimethylphenol photooxidation reaction (CHA-HC)

[0084]

[0085]

[0086] Example 8

[0087] At 50mW / cm 2 Under the irradiation of white LED light, the raw material 2,3,5-trimethylphenol (substrate concentration is 10mM) was dissolved in 50mL of ethanol and water (volume ratio is 4:1) mixed solvent, and the bamboo red fungus derivative CHA-HC or EDA-HB was added as a photosensitizer (concentration is 0.10mM), and oxygen was continuously introduced into the transparent quartz reaction container. The reaction was stirred at room temperature (30°C) for 2,4,6,8,12h. The solvent was removed by vacuum distillation, and the crude product was separated by column chromatography (petroleum ether / ethyl acetate, 5:1, v / v) to obtain 2,3,5-trimethylbenzoquinone, and the reaction yield is shown in Table 7.

[0088] Table 7: Effect of reaction time on the yield of 2,3,5-trimethylphenol photooxidation reaction (CHA-HC)

[0089]

[0090] The hypocrellin derivatives CHA-HC or EDA-HB can efficiently generate singlet oxygen under light. The possible mechanism of the photooxidative synthesis of 2,3,5-trimethylphenol is as follows: singlet oxygen reacts with 2,3,5-trimethylphenol through a 1,4-cycloaddition reaction to form a cycloperoxide intermediate, which is extremely unstable and can be decomposed into the corresponding hydroperoxide and then lose a molecule of water to generate 2,3,5-trimethylbenzoquinone.

[0091]

[0092] After optimizing the above experimental conditions, we chose 50mW / cm2 White light LED was used as the irradiation light source, because the photosensitizer CHA-HC or EDA-HB used in the hypocrellin has very strong absorption in the visible light region, which matches well with the absorption band of white light LED. By fully optimizing different reaction conditions, such as the concentration of substrate, different solvents, concentration of photosensitizer, reaction time, reaction temperature, etc., the target product 2,3,5-trimethylbenzoquinone was synthesized with high yield and high selectivity.

[0093] The yield of the present invention can reach 85%, while the yield of the traditional oxidation synthesis method is 30-40%, and the yield of the sunlight synthesis method of Suchard et al. is about 50%. The method of the present invention greatly reduces the by-products of the reaction and saves operation steps and energy, making the product easy to separate and purify, while obtaining higher returns and having great commercial value.

[0094] Comparative Example 1

[0095] At 50mW / cm 2 Under the irradiation of white light LED lamp, the raw material 2,3,5-trimethylphenol (substrate concentration is 10mM) is dissolved in 50mL of a mixed solvent of ethanol and water (volume ratio is 4:1). In the absence of a photosensitizer, oxygen is continuously introduced into the transparent quartz reaction container. When the reaction temperature is room temperature and stirring is carried out, almost no product is obtained.

[0096] Comparative Example 2

[0097] At 50mW / cm 2 Under the irradiation of white LED light, the raw material 2,3,5-trimethylphenol (substrate concentration is 10mM) is dissolved in 50mL of ethanol and water (volume ratio is 4:1) mixed solvent, and HA or HB or HpD are added as photosensitizers (concentration is 0.10mM), oxygen is continuously introduced into the transparent quartz reaction container, and the reaction is stirred for 12h at room temperature. The solvent is removed by vacuum distillation, and the crude product is separated by column chromatography (petroleum ether / ethyl acetate, 5:1, v / v) to obtain 2,3,5-trimethylbenzoquinone, and the reaction yields are 43%, 45% and 32%, respectively.

[0098] It can be seen from Comparative Examples 1 and 2 that photosensitizers are essential for the oxidation of 2,3,5-trimethylphenol. No product is generated without the participation of photosensitizers. Under the same conditions, the yield of HA, HB or HpD as photosensitizers is also low, while the maximum yield of CHA-HC or EDA-HB as photosensitizers can be as high as 85%, which has high practical value.

[0099] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A compound represented by formula (I) or its enol tautomer: in, When A does not exist; R is -COCH3; When A is selected from a 5-7 membered cycloalkane fused to an adjacent piperazine ring; R is H.

2. The compound according to claim 1 or its enol tautomer, characterized in that: The 5-7 membered cycloalkane fused with the adjacent piperazine ring is selected from cyclohexane, cyclopentane and cycloheptane fused with the adjacent piperazine ring.

3. The compound according to claim 1 or its enol tautomer, characterized in that: The compound represented by formula (I) has a structure represented by formula (I-1) or (I-2): Wherein, in formula (I-1), A is selected from a 5-7 membered cycloalkane fused to an adjacent piperazine ring; and in formula (I-2), A does not exist.

4. The compound according to claim 1 or its enol tautomer, characterized in that: The structure of the compound represented by formula (I) is shown below:

5. A method for preparing a compound according to any one of claims 1 to 4 or its enol tautomer, characterized in that: The following steps are involved: The compound represented by formula (II) is reacted with compound 2 to obtain the compound represented by formula (I); Wherein, A and R have the definitions described in any one of claims 1-4.

6. The preparation method according to claim 5, characterized in that: The reaction temperature is 40 to 120° C. And / or, the reaction time is 6 to 48 hours; And / or, the reaction is carried out in a solvent, and the solvent is an organic solvent, or a mixed solvent of an organic solvent and water.

7. The preparation method according to claim 5, characterized in that: The reaction temperature is 50-100°C; And / or, the reaction time is 12 to 42 hours; And / or, the reaction is carried out in a solvent, and the solvent is one or more of acetonitrile, tetrahydrofuran, pyridine, N,N-dimethylformamide, dimethyl sulfoxide, methanol or ethanol.

8. The preparation method according to claim 5, characterized in that: When R in the compound of formula (I) is H (i.e., formula (I-1)), the following steps are included: Wherein, A has the definition as described in claim 5; 1) Compound HB reacts with an alkaline aqueous solution to obtain compound HC; 2) Compound HC reacts with compound 2 to obtain a compound represented by formula (I-1).

9. The preparation method according to claim 8, characterized in that: In step 1), the base is sodium hydroxide, lithium hydroxide, potassium hydroxide, potassium carbonate, or cesium carbonate; And / or, in step 1), the reaction temperature is 60-150°C; And / or, in step 1), the reaction time is 2 to 24 hours.

10. The preparation method according to claim 8, characterized in that: In step 1), the mass concentration of the alkaline aqueous solution is 0.5-5%; And / or, in step 1), the reaction temperature is 80-120°C; And / or, in step 1), the reaction time is 6-12h.

11. Use of the compound according to any one of claims 1 to 4 or its enol tautomer as a photosensitizer in the preparation of 2,3,5-trimethylbenzoquinone.

12. A method for preparing 2,3,5-trimethylbenzoquinone, characterized in that: The preparation comprises the following steps: mixing 2,3,5-trimethylphenol with the compound according to any one of claims 1 to 4 or its enol tautomer, and reacting them under light and oxygen-containing atmosphere to obtain 2,3,5-trimethylbenzoquinone; And / or, the light source is 50mW / cm 2 White LED light source; And / or, the reaction temperature is 10-40°C.

13. The preparation method according to claim 12, characterized in that: The method comprises the following steps: dissolving 2,3,5-trimethylphenol and the compound according to any one of claims 1 to 4 or its enol tautomer in a mixed solution of ethanol and water to obtain a reaction solution, transferring the reaction solution to a photochemical reactor, continuously introducing oxygen into the photochemical reaction container, irradiating the reaction solution with a light source and continuously stirring to react, and obtaining a product 2,3,5-trimethylbenzoquinone.

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