A synthetic method for the azotization of phenols

Abstract

This invention discloses a method for activating aryltriazenes without accelerators. Aryl azo ions are generated under the catalysis of light, electricity, flow chemistry, ultrasound, microwave, and mechanochemistry, leading to azotization of phenols and the formation of a series of aryl azo-substituted phenols. Compared with previously reported methods for preparing phenolic compounds by azotization, this invention avoids the use of acid to activate aryltriazenes, allowing the activation reaction to occur under mild conditions, thereby reducing the formation of byproducts. The advantages of this invention include: visible light-promoted activation of aryltriazenes, resulting in high reactivity and a broad substrate range; electrochemical, ultrasonic, and microwave catalytic activation of aryltriazenes, leading to high reaction efficiency; high yield and large-scale preparation via flow chemistry; and high efficiency and large-scale preparation via mechanochemistry, achieved without solvents.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, specifically to a method in which aryltriazine is generated under the action of light, electricity, flow chemistry, mechanochemistry, ultrasound and microwave without a promoter, and then α-aryl azo ions are formed with β-naphthol to obtain (E)-1-(arylazo)naphth-2-phenol derivatives. Background Technology

[0002] Aryltriazine in Lewis acid or Results from a range of spontaneous skeletal muscles (Kumar,S.Pandey,AK)Singh,R.Singh,KNEu r.J.Org.Chem.2018,43,5942;Vishwakarma,RK;Kumar,S.Sharma,AK,Singh h,R.Singh,KNChemistrySelect2019,4,4064;Saeki,T.Son,EC;Tamao,K.Org.Lett.2004,6,617;Liu,C.-Y.Gavryushin,A.Knochel,P.Chem.Asian J.2007,2,1020;Nan,G.Zhu,F.Wei,Z.Chin.J.Chem.2011,29,72;Chadha,N.Silakari,O.Eur.J.Med.Chem.2017,134 ,159;Gharibo,C.Argoff,C.Markenson,JAWebster,L.Nezzer,J.Solorio,D.Lauterio,M.Young,C.Clin.J.Pain 2018,34,138Mirzaei,H.Shokrzadeh,M.Modanloo,M.Ziar,A.Riazi,GH;Emami,S.Bioorgan.Chem.2017,75,86 Huo,JQChen,L.Si,HLYuan,STLi,JHDong,HJHu,SQHuo,JLKou,SXiong,DMao,JYZhang,JLJAgric.Food Chem.2022,70,6982;Liu,C.Miao,T.Zhang,L.Li,P..Zhang,Y.,Wang,L.Chem.Asian J.2014,9,2584;Wang,R.Falck,JROrg.Chem.Front.2014,1,1029Chaubey,NRVishwakarma,RKSingh,KNChemistrySelect 2019,4,8522;Dai,WC;Wang,ZXOrg.Chem.Front.2017,4,1281Liu,C.Wang,Z.Wang,L.Li,P.Zhang,Y.Org.Biomol.Chem.2019,17,9209;Barragan,E.;Poyil,AN;Yang,C.-H.;Wang,H.;Bugarin,A.Org.Chem.Front.2019,6,152;Yin,Z.;Wang,Z.;W.E. J.Org.Chem.2017,3992;Yin,Z.;Wang,Z.;Wu,X.-F.Org.Lett.2017,19,6232;Chand,S.;Kumar,S.;Singh,R.;Singh,ChemistrySelectNC 2019,4,718;Wippert,NA;Jung,N.;. S.ACS Comb.Sci.2019,21,568;Barragan,E.;Noonikara-Poyil,A.;Bugarin,A.Asian J.Org.Chem.2020,9,593;Pandey,AK;Kumar,S.;Singh,R.;Singh,KNTetrahedron 2018,74,6704.Qi,X.-X.;Jiang,L.-B.;Zhou,C.;Peng,J.-B.;Wu,X.-F.ChemistryOpen 2017,6,345;Cao,D.;Zhang,Y.;Liu,C.;Wang,B;Sun,Y.;Abdukadera,A.;Hu,H.;Liu,Q.Org. Lett.2016,18,2000; Zhang, Y.; Liu, Y.; Ma, X.; Ma, X.; Wang, B.; Li, H.; Huang, Y.; Liu, C. Dyes Pigm.2018,158,438;Liu,Y.;Ma,X.;Wu,G.;Liu,Z.;Yang,X.;Wang,B.;Liu,C.;Zhang,Y.;Huang,Y. In 2021, Jewett's group reported that aryltriazenes could be activated under ultraviolet light without a promoter, achieving azotization (Davis, GJ; Townsend, JA; Morrow, MG; Hamie, M.; Shepard, AJ; Hsieh, CC.; Marty, MT; Jewett, JCBioconjugate Chem. 2021, 32, 2432). This invention achieves azotization under promoter-free conditions using visible light catalysis, electrocatalysis, flow chemistry, mechanochemistry, sonicochemistry, and microwave methods. These methods are characterized by simple operation, green efficiency, environmental friendliness, readily available raw materials, good versatility, and the ability to prepare in large quantities. Summary of the Invention

[0003] This invention utilizes photocatalysis, electrochemistry, flow chemistry, ultrasound, microwave catalysis, and mechanochemistry to activate aryltriazene and azotize β-naphthol, achieving the green and efficient synthesis of (E)-1-(arylazo)naphth-2-phenol derivatives under conditions with accelerators or even without solvents.

[0004] This invention activates aryltriazine into aryldiazo cations through physical forces, overcoming the shortcomings of traditional triazine reactions under acid-promoted conditions. It provides a non-toxic, harmless, and green synthesis method for the azotization of biomolecules containing phenolic hydroxyl groups.

[0005] This method was used to prepare (E)-1-(arylazo)naphthalene-2-phenolic compound (III) in the following reaction formula;

[0006] The reaction process is shown in the following reaction formula;

[0007]

[0008] Wherein Ar represents an aryl or phenyl group containing different substituents, the substituents being one or more of hydrogen, methyl, methoxy, isopropyl, tert-butylphenyl, and halophenyl, and the halogen being one of fluorine, chlorine, bromine, and iodine.

[0009] As shown in the above reaction formula, this invention uses β-naphthol (Ⅰ) and aryltriazine compound (Ⅱ) as raw materials and acetonitrile as solvent to obtain (E)-1-(arylazo)naphth-2-phenol compound (Ⅲ) under photocatalysis. In the reaction, the light used is one of violet light, ultraviolet light, blue light, green light, red light, and white light, with violet light being the preferred light.

[0010] A method for synthesizing the azotization of phenols, characterized by: mixing β-naphthol and aryltriazene to obtain (E)-1-(arylazo)naphth-2-phenol compound, specifically the reaction formula is as follows:

[0011]

[0012] Wherein Ar represents an aryl or phenyl group containing different substituents, the substituents being one or more of hydrogen, methyl, methoxy, isopropyl, tert-butylphenyl, and halophenyl, and the halogen being one of fluorine, chlorine, bromine, and iodine.

[0013] β-naphthol (Ⅰ) and aryltriazine (Ⅱ) in a solvent under visible light yield compound (Ⅲ) (E)-1-(arylazo)naphth-2-phenol, with a molar ratio of β-naphthol (Ⅰ) to aryltriazine (Ⅱ) of 1:1-2 and a reaction time of 10-15 h.

[0014] β-naphthol (Ⅰ) and aryltriazine (Ⅱ) in a solvent, and tetrabutylammonium iodide under the action of an electrode, yield compound (Ⅲ) (E)-1-(arylazo)naphth-2-phenol in the following reaction formula, wherein the molar ratio of β-naphthol (Ⅰ) to aryltriazine (Ⅱ) is 1:1-2; the cathode of the electrode is one or more of C, Ni, Pt, Ag, and Cu (preferably Ni), the anode of the electrode is carbon, the molar ratio of tetrabutylammonium iodide to β-naphthol (Ⅰ) is 1:1-2 (preferably 1:1.2), the constant current is 5-10 mA, and the reaction time is 3-5 h.

[0015] β-Naphthol (Ⅰ) dissolved in solvent 1 and aryltriazine (Ⅱ) dissolved in solvent 2 are reacted under flow chemistry to obtain compound (Ⅲ) (E)-1-(arylazo)naphth-2-phenol in the following reaction formula. The molar ratio of β-naphthol (Ⅰ) to aryltriazine (Ⅱ) is 1:1-2 (preferably 1:1.2), and the reaction is carried out at room temperature at a flow rate of 0.2-0.5 ml / min. Both solvent 1 and solvent 2 are acetonitrile, and the volume ratio of solvent 1 to solvent 2 is 1:1-2. The specific reaction process is shown in the following reaction formula.

[0016]

[0017] Wherein Ar represents an aryl or phenyl group containing different substituents, the substituents being one or more of hydrogen, methyl, methoxy, isopropyl, tert-butylphenyl, and halophenyl, and the halogen being one of fluorine, chlorine, bromine, and iodine.

[0018] β-naphthol (Ⅰ) and aryltriazine (Ⅱ) react under mechanochemical conditions to obtain compound (Ⅲ) (E)-1-(arylazo)naphth-2-phenol in the following reaction formula; the molar ratio of β-naphthol (Ⅰ) to aryltriazine (Ⅱ) is 1:1-2 (preferably 1:1.2), and the specific reaction process is shown in the following reaction formula; the mechanochemical reaction is ball milling, in which stainless steel balls (20 mm) are used, the rotation speed is 320 r, and the reaction time is 3 h.

[0019] β-naphthol (Ⅰ) and aryltriazine (Ⅱ) are reacted in a solvent under ultrasonic treatment to obtain compound (Ⅲ) (E)-1-(arylazo)naphth-2-phenol in the following reaction formula, wherein the molar ratio of β-naphthol (Ⅰ) to aryltriazine (Ⅱ) is 1:1-2 (preferably 1:1.2), the ultrasonic power is 700-1000w, and the reaction time is 2-5 hours.

[0020] Using β-naphthol (Ⅰ) and aryltriazine (Ⅱ) in a solvent under microwave irradiation, compound (Ⅲ) (E)-1-(arylazo)naphth-2-phenol is obtained in the following reaction formula, wherein the molar ratio of β-naphthol (Ⅰ) to aryltriazine (Ⅱ) is 1:1-2 (preferably 1:1.2); the temperature is 60-80℃, and the reaction time is 8-15 min.

[0021] The reaction includes the following steps:

[0022] The light is one or more of the following: visible light, violet light, ultraviolet light, blue light, red light (infrared), and white light (preferably violet light).

[0023] The reaction is carried out in a solvent, namely acetonitrile, and the amount of solvent added is 1-6 mL per 0.2 mmol β-naphthol.

[0024] The synthetic reaction of this invention includes the following steps:

[0025] Synthesis of (E)-1-(arylazo)naphthyl-2-phenol compound (III):

[0026] β-naphthol (Ⅰ) (0.2 mmol) and aryltriazine (Ⅱ) (0.3 mmol) were added sequentially to a quartz tube and dissolved in acetonitrile (1 mL). After reacting under ultraviolet light for 12 h, the above-mentioned reaction product (E)-1-(arylazo)naphth-2-phenol (Ⅲ) compound was obtained.

[0027] β-naphthol (Ⅰ) (0.3 mmol), aryltriazine (Ⅱ) (0.45 mmol), and tetrabutylammonium iodide (0.3 mmol) were added sequentially to an electrochemical reaction flask and dissolved in acetonitrile (4 mL). C-Ni was used as the reaction electrode, and the current was 4 mA. After reacting for 4 h, the above-mentioned reaction product (E)-1-(arylazo)naphthol-2-phenol (Ⅲ) compound was obtained.

[0028] Two beakers were used to dissolve β-naphthol (Ⅰ) (0.3 mmol) in acetonitrile (6 mL) in one beaker, and aryltriazine (Ⅱ) (0.45 mmol) in acetonitrile (6 mL) in the other beaker. The reaction solutions were added to parallel reaction channels, and the flow rate of the micro-injection pump was 0.2 mL / min. The reaction was carried out in a flow chemistry synthesizer for 30 min. After the reaction was completed, the above reaction product (E)-1-(arylazo)naphthol-2-phenol (Ⅲ) compound was obtained.

[0029] β-naphthol (Ⅰ) (0.3 mmol), aryltriazine (Ⅱ) (0.36 mmol), and stainless steel balls were added sequentially to a ball mill jar. The rotation speed was set to 320 r, and the reaction was carried out in a planetary ball mill for 3 h to obtain the above reaction product (E)-1-(arylazo)naphth-2-phenol (Ⅲ) compound.

[0030] β-naphthol (Ⅰ) (0.3 mmol) and aryltriazine (Ⅱ) (0.45 mmol) were added sequentially to a reaction flask and dissolved in acetonitrile (6 mL). The reaction solution was placed in an ultrasonic reactor with a reaction power of 800 W. After 2 h of reaction, the above-mentioned reaction product (E)-1-(arylazo)naphthol-2-phenol (Ⅲ) compound was obtained.

[0031] β-naphthol (Ⅰ) (0.2 mmol) and aryltriazine (Ⅱ) (0.3 mmol) were added sequentially to a reaction tube and dissolved in acetonitrile (1 mL). The reaction solution was placed in a microwave synthesizer and reacted at 60 °C for 10 min to obtain the above-mentioned reaction product (E)-1-(arylazo)naphthol-2-phenol (Ⅲ) compound.

[0032] This invention utilizes photocatalysis, electrochemistry, flow chemistry, mechanochemistry, ultrasound, and microwave methods to achieve the azotization of naphthol, without requiring acid as a promoter to activate triazene. The highly efficient photocatalytic and ultrasound methods provide efficient and green synthetic approaches for the intracellular azotization of biomolecules, peptides, or proteins; electrocatalysis, flow chemistry, ultrasound, and mechanochemistry methods enable large-scale preparation. All these methods offer advantages such as mild, green, and efficient reaction conditions, inexpensive and readily available raw materials, simple operation, a broad substrate range, and the ability to produce in large quantities. Attached Figure Description

[0033] Figure 1 The image shows the 1H NMR spectrum of the product (E)-1-(4-tolueneazo)naphthol from Example 1.

[0034] Figure 2 This is the 1H NMR spectrum of the product (E)-1-(phenylazo)naphthol-2-phenol from Example 16.

[0035] Figure 3 This is the 1H NMR spectrum of the photocatalytic (E)-1-(3-tolueneazo)naphthol-2-phenol produced in Example 17.

[0036] Figure 4 This is the 1H NMR spectrum of the product (E)-1-(2-tolueneazo)naphthol from Example 18.

[0037] Figure 5 The image shows the 1H NMR spectrum of the product (E)-1-((4-methoxyphenyl)azo)naphth-2-phenol from Example 19.

[0038] Figure 6 This is the 1H NMR spectrum of the product (E)-1-((4-isopropylphenyl)azo)naphth-2-phenol from Example 20.

[0039] Figure 7 The image shows the 1H NMR spectrum of the product (E)-1-((4-tert-butylphenyl)azo)naphthyl-2-phenol from Example 21.

[0040] Figure 8 The image shows the 1H NMR spectrum of the product (E)-1-((4-bromophenyl)azo)naphth-2-phenol from Example 22.

[0041] Figure 9 This is a reaction structure diagram. Detailed Implementation

[0042] The present invention will be further described in detail below with reference to specific embodiments. However, the scope of protection of the present invention is not limited to these embodiments. All variations and advantages that can be conceived by those skilled in the art without departing from the spirit and scope of the inventive concept are included in the present invention and are protected by the appended claims. The processes, conditions, reagents, experimental methods, etc., used to implement the present invention, except as specifically mentioned below, are all common knowledge and general knowledge in the art, and the present invention does not have any particular limitations. The data given in the following embodiments include specific operations, reaction conditions, and products. Product purity was determined by NMR.

[0043] Example 1: Photocatalytic synthesis of (E)-1-(4-tolueneazo)naphthol-2-phenol

[0044]

[0045] β-Naphthol (1a) (0.2 mmol, 28.8 mg) and 4-tolyltriazene (2a) (0.3 mmol, 56.7 mg) dissolved in acetonitrile (1 mL) were added to a dry, clean quartz tube. The reaction was carried out under ultraviolet light (10 W) for 12 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (48.3 mg, 92% yield). The target product was confirmed by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HMR). The parameters of the obtained product were as follows: 1 H NMR (400MHz, CDCl3) δ16.15(s,1H),8.61(d,J=8.4Hz,1H),7.72(d,J=9.2Hz,1H),7.67(d,J=8.4Hz,2H),7.62 (d,J=8Hz,1H),7.53-7.58(m,1H),7.37-7.41(m,1H),7.28(d,J=8Hz,2H),6.93(d,J=9.2Hz,1H),2.41(s,3H).

[0046] Example 2

[0047] The reaction steps and operating conditions were the same as in Example 1, except that the light source was violet light (10W) instead of ultraviolet light (10W). The reaction was stopped, and the target product 3a (36.8 mg, 70% yield) was obtained after the same post-treatment as described above. This demonstrates that using ultraviolet light as the light source yields the target product in a better rate. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0048] Example 3

[0049] The reaction steps and operating conditions were the same as in Example 1, except that the light source was violet light (10W) instead of blue light (10W). The reaction was stopped, and the target product 3a (26.0 mg, 50% yield) was obtained after the same post-treatment as described above. This demonstrates that a blue light source can yield the target product in a better yield. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0050] Example 4

[0051] The reaction steps and operating conditions were the same as in Example 1, except that the light source was changed from green light (10W) to violet light (10W). The reaction was stopped, and the target product 3a (3.3mg, yield 6%) was obtained after the same post-treatment as described above, indicating that the yield of the target product was low when the light source was green light.

[0052] Example 5

[0053] The reaction steps and operating conditions were the same as in Example 1, except that the infrared light source (10W) was replaced by red light (10W) in the reaction. The reaction was stopped, and the target product 3a (14.1 mg, yield 27%) was obtained after the same post-treatment as described above, indicating that the yield of the target product was low when the light source was infrared.

[0054] Example 6

[0055] The reaction steps and operating conditions were the same as in Example 1, except that white light (10W) was used as the light source instead of violet light (10W) in the reaction. The reaction was stopped, and the target product 3a (34.1 mg, yield 65%) was obtained after the same post-treatment as described above. This shows that when white light is used as the light source, the target product can be obtained in a better yield.

[0056] Example 7

[0057] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was carried out in darkness. The reaction was stopped, and after the same procedures as described above, the target product 3a was not obtained. This demonstrates that a light source is essential.

[0058] Example 8: Electrocatalytic synthesis of (E)-1-(4-tolueneazo)naphthol-2-phenol

[0059]

[0060] In a dry, clean, diaphragm-free electrochemical reaction flask, β-naphthol (1a) (0.3 mmol, 43.2 mg), 4-tolyltriazene (2a) (0.45 mmol, 85.1 mg), and tetrabutylammonium iodide (0.3 mmol, 110.8 mg) were dissolved in acetonitrile (4 mL). Carbon was used as the anode (8 mm long × 2 mm wide × 50 mm high), and nickel as the cathode (8 mm long × 2 mm wide × 50 mm high). The lower ends of the anode and cathode were inserted 8 mm below the liquid surface, with a 5 mm distance between them. The planes containing the length and height of the two electrodes (anode and cathode) were parallel to each other (the area of ​​the opposing surfaces of the anode and cathode in the reaction solution was 64 mm²). 2 The reaction was carried out at a constant current of 6 mA for 4 h. After the reaction was complete, 5 mL of water was added to the reaction system to quench the reaction, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (78.0 mg, 99% yield). The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0061] Example 9

[0062] The reaction steps and operating conditions were the same as in Example 8, except that silver was used instead of nickel as the cathode electrode. The reaction was stopped, and the target product 3a (78.3 mg, 100% yield) was obtained after the same post-treatment as described above, demonstrating that silver cathode electrode yields the target product in the optimal rate. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0063] Example 10

[0064] The reaction steps and operating conditions were the same as in Example 8, except that platinum was used instead of nickel as the cathode electrode. The reaction was stopped, and the target product 3a (78.5 mg, 100% yield) was obtained after the same post-treatment as described above, demonstrating that platinum cathode electrode yields the target product in the optimal yield. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0065] Example 11

[0066] The reaction steps and operating conditions were the same as in Example 8, except that carbon was used instead of nickel as the cathode electrode. The reaction was stopped, and the target product 3a (46.5 mg, yield 59%) was obtained after the same post-treatment as described above, demonstrating that a carbon cathode electrode can yield the target product in a moderate yield. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0067] Example 12: Synthesis of (E)-1-(4-tolueneazo)naphthol by flow chemistry

[0068]

[0069] In a clean, dry beaker, β-naphthol (1a) (0.3 mmol, 43.2 mg) was dissolved in acetonitrile (6 mL). Separately, 4-tolyltriazene (2a) (0.45 mmol, 85.1 mg) was dissolved in acetonitrile (6 mL). These reaction solutions were added separately to parallel reaction channels, with a micro-pump flow rate of 0.2 mL / min. After the reaction was complete, 5 mL of water was added to quench the reaction mixture. The aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1–30:1, v / v) to obtain a red solid (77.8 mg, 99% yield). The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0070] Example 13: Synthesis of (E)-1-(4-tolueneazo)naphthol by mechanochemical method

[0071]

[0072] β-Naphthol (1a) (0.3 mmol, 43.2 mg) and 4-tolyltriazene (2a) (0.36 mmol, 68.0 mg) were added to a dry, clean ball mill jar. A stainless steel ball (20 mm) was used, and the mixture was reacted at 320 rpm for 3 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1–30:1, v / v) to obtain a red solid (74.8 mg, 95% yield). The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0073] Example 14: Synthesis of (E)-1-(4-tolueneazo)naphthol by ultrasonic method

[0074]

[0075] In a clean, dry round-bottom flask, β-naphthol (1a) (0.3 mmol, 43.2 mg) and 4-tolyltriazene (2a) (0.45 mmol, 85.1 mg) were dissolved in acetonitrile (6 mL). The reaction was carried out at 800 W for 3 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (70.0 mg, 89% yield). The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0076] Example 15: Microwave synthesis of (E)-1-(4-tolueneazo)naphthol-2-phenol

[0077]

[0078] In a clean, dry round-bottom flask, β-naphthol (1a) (0.2 mmol, 28.8 mg) and 4-tolyltriazene (2a) (0.3 mmol, 56.7 mg) were dissolved in acetonitrile (1 mL) and reacted at 60 °C for 10 min. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (35.6 mg, 68% yield). The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0079] Example 16: Photocatalytic synthesis of (E)-1-(phenylazo)naphthyl-2-phenol

[0080]

[0081] β-Naphthol (1a) (0.2 mmol, 28.8 mg) and 4-phenyltriazine (2b) (0.3 mmol, 52.5 mg) dissolved in acetonitrile (1 mL) were added to a dry, clean quartz tube. The reaction was carried out under ultraviolet light (10 W) for 12 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (44.0 mg, yield 88%). The target product was confirmed by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). The parameters of the obtained product were as follows: 1 H NMR (400MHz, CDCl3) δ16.24(s,1H),8.57-8.52(m,1H),7.72(ddd,J=12.9,7.0,5.3Hz,3H),7.59(d,J=7.8Hz,1H),7.55(dd d,J=8.3,7.1,1.3Hz,1H),7.51-7.45(m,2H),7.39(ddd,J=7.9,7.2,1.2Hz,1H),7.33-7.27(m,1H),6.86(d,J=9.4Hz,1H).

[0082] Example 17: Photocatalytic synthesis of (E)-1-(3-tolueneazo)naphthol-2-phenol

[0083]

[0084] β-Naphthol (1a) (0.2 mmol, 28.8 mg) and 3-tolyltriazene (2c) (0.3 mmol, 56.7 mg) were dissolved in acetonitrile (1 mL) in a dry, clean quartz tube. The reaction was carried out under ultraviolet light (10 W) for 12 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (28.7 mg, yield 55%). The target product was confirmed by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). The parameters of the obtained product were as follows: 1H NMR (400MHz, CDCl3) δ16.17(s,1H),8.57(d,J=8.2Hz,1H),7.71(d,J=9.5Hz,1H),7.61-7 .53(m,4H),7.43-7.32(m,2H),7.12(d,J=7.3Hz,1H),6.87(d,J=9.4Hz,1H),2.46(s,3H).

[0085] Example 18: Photocatalytic synthesis of (E)-1-(2-tolueneazo)naphthyl-2-phenol

[0086]

[0087] β-Naphthol (1a) (0.2 mmol, 28.8 mg) and 2-tolyltriazine (2d) (0.3 mmol, 56.7 mg) were dissolved in acetonitrile (1 mL) in a dry, clean quartz tube. The reaction was carried out under ultraviolet light (10 W) for 12 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (39.8 mg, yield 76%). The target product was confirmed by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). The parameters of the obtained product were as follows: 1 H NMR (400MHz, CDCl3) δ8.59(d,J=8.2Hz,1H),8.08(d,J=8.1Hz,1H),7.73(d,J=9.5Hz,1H),7.63-7.53(m, 2H),7.44-7.33(m,2H),7.29(d,J=7.4Hz,1H),7.21(t,J=7.3Hz,1H),6.88(d,J=9.5Hz,1H),2.56(s,3H).

[0088] Example 19: Photocatalytic synthesis of (E)-1-((4-methoxyphenyl)azo)naphthyl-2-phenol

[0089]

[0090] β-Naphthol (1a) (0.2 mmol, 28.8 mg) and 4-methoxyphenyltriazine (2e) (0.3 mmol, 61.5 mg) dissolved in acetonitrile (1 mL) were added to a dry, clean quartz tube. The reaction was carried out under ultraviolet light (10 W) for 12 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (29.0 mg, yield 52%). The target product was confirmed by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HMR). The parameters of the obtained product were as follows: 1 H NMR (400MHz, CDCl3) δ15.71 (s, 1H), 8.71 (d, J = 8.5Hz, 1H), 7.85-7.80 (m, 2H), 7.76 (d, J = 9.2Hz, 1H), 7. 70(d,J=8.0Hz,1H),7.58(ddd,J=8.3,7.0,1.3Hz,1H),7.41(m,1H),7.04(t,J=8.8Hz,3H),3.89(s,3H).

[0091] Example 20: Photocatalytic synthesis of (E)-1-((4-isopropylphenyl)azo)naphthyl-2-phenol

[0092]

[0093] β-Naphthol (1a) (0.2 mmol, 28.8 mg) and 4-isopropylphenyltriazine (2f) (0.3 mmol, 65.1 mg) were dissolved in acetonitrile (1 mL) in a dry, clean quartz tube. The reaction was carried out under ultraviolet light (10 W) for 12 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (33.8 mg, yield 58%). The target product was confirmed by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). The parameters of the obtained product were as follows: 1H NMR (400MHz, CDCl3) δ16.19(s,1H),8.61(d,J=8.1Hz,1H),7.71(dd,J=8.8,6.2Hz,3H),7.62(d,J=7.8Hz,1H),7.56(t, J=7.6Hz,1H),7.39(t,J=7.5Hz,1H),7.35(d,J=8.4Hz,2H),6.93(d,J=9.4Hz,1H),2.98(m,1H),1.31(d,J=6.9Hz,6H).

[0094] Example 21: Photocatalytic synthesis of (E)-1-((4-isopropylphenyl)azo)naphthyl-2-phenol

[0095]

[0096] β-Naphthol (1a) (0.2 mmol, 28.8 mg) and 4-tert-butylphenyltriazine (2 g) (0.3 mmol, 69.3 mg) were dissolved in acetonitrile (1 mL) in a dry, clean quartz tube. The reaction was carried out under ultraviolet light (10 W) for 12 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (37.6 mg, yield 62%). The target product was confirmed by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HMR). The parameters of the obtained product were as follows: 1 H NMR (400MHz, CDCl3) δ16.22(s,1H),8.60(d,J=7.8Hz,1H),7.71(m,3H),7.62(d,J=7.8Hz,1H) ,7.59-7.53(m,1H),7.53-7.48(m,2H),7.42-7.37(m,1H),6.92(d,J=9.4Hz,1H),1.38(s,9H).

[0097] Example 22: Photocatalytic synthesis of (E)-1-((4-bromophenyl)azo)naphthyl-2-phenol

[0098]

[0099] β-Naphthol (1a) (0.2 mmol, 28.8 mg) and 4-bromophenyltriazine (2h) (0.3 mmol, 75.9 mg) were dissolved in acetonitrile (1 mL) in a dry, clean quartz tube. The reaction was carried out under ultraviolet light (10 W) for 12 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (32.1 mg, yield 49%). The target product was confirmed by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). The parameters of the obtained product were as follows: 1 H NMR (400MHz, CDCl3) δ16.05 (s, 1H), 8.53 (d, J = 8.2Hz, 1H), 7.73 (d, J = 9.4Hz, 1H), 7.64-7.52 (m, 6H), 7.41 (t, J = 7.4Hz, 1H), 6.87 (d, J = 9.4Hz, 1H).

[0100] Example 23: Synthesis of (E)-1-(phenylazo)naphthyl-2-phenol by mechanochemical method

[0101]

[0102] β-Naphthol (1a) (0.3 mmol, 43.2 mg) and phenyltriazine (2b) (0.36 mmol, 63.0 mg) were added to a dry, clean ball mill jar with a 20 mm stainless steel ball and the reaction was carried out at 320 rpm for 3 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1-30:1, v / v) to obtain a red solid (66.9 mg, 90% yield). The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0103] Example 24: Synthesis of (E)-1-((4-methoxyphenyl)azo)naphthol by mechanochemical method

[0104]

[0105] β-Naphthol (1a) (0.3 mmol, 43.2 mg) and 4-methoxyphenyltriazine (2c) (0.36 mmol, 73.8 mg) were added to a dry, clean ball mill jar. A stainless steel ball (20 mm) was used, and the mixture was reacted at 320 rpm for 3 h. After the reaction was complete, 5 mL of water was added to quench the reaction mixture, and the aqueous mixture was extracted with ethyl acetate (3 × 5 mL, 3 times, 5 mL each time). After extraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether / ethyl acetate 50:1–30:1, v / v) to obtain a red solid (82.1 mg, 98% yield). The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0106] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural or procedural transformations made based on the content of the present invention's specification and drawings, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. A method for synthesizing the azotization of phenols, characterized in that: exist β -Naphthol and aryltriazine are mixed to obtain ( E The compound is 1-(arylazo)naphth-2-phenol, and the specific reaction formula is as follows: Ar represents an aryl group containing different substituents, the substituents being one or more of hydrogen, methyl, methoxy, isopropyl, tert-butylphenyl, and halophenyl, and the halogen being one of fluorine, chlorine, bromine, and iodine. β - Naphthol (Ⅰ) and aryltriazene (Ⅱ), under mechanochemical action, yield the following reaction ( E Compound (III) of 1-(arylazo)naphth-2-phenol. β - The molar ratio of naphthol (Ⅰ) and aryltriazine (Ⅱ) is 1:1-2; the specific reaction process is shown in the following reaction formula; the mechanochemical method is ball milling, in which stainless steel balls (20 mm) are used, the rotation speed is 320 r, and the reaction time is 3 h.

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