A process for the preparation of tert-butyl phenyl ethers and derivatives thereof

Abstract

The present application relates to a kind of preparation of tert-butyl phenyl ether and its derivatives, it is characterized in that with different substituent phenol as raw material, using metal catalyst activates di-tert-butyl dicarbonate, preparation of tert-butyl phenyl ether and its derivatives, the method includes: (1) after adding different substituent phenyl phenol with metal catalyst in organic solvent, di-tert-butyl dicarbonate is added to occur nucleophilic substitution reaction and obtain tert-butyl phenyl ether;(2) solvent is removed after reaction ends, and the product is extracted, washed, dried and the like to obtain high-purity tert-butyl phenyl ether or its derivative product.The method of the present application has the advantages of simple synthesis process, mild reaction condition, fast reaction rate, wide range of use and raw material easy to obtain.

Description

Technical Field

[0001] This invention relates to the preparation technology of functional organic compounds, specifically a method for preparing tert-butylphenyl ethers and their derivatives. Background Technology

[0002] tert-butylphenyl ether and its derivatives are functional organic compounds and important components in pesticides, pharmaceuticals, and fuel additives. For example, tert-butylphenyl ether, as a fuel additive, has a good octane rating and can inhibit the production of peroxides; tert-butyl(4-vinylphenyl) ether, as a component of photoresist resin monomers, is commonly used in fields such as chips and integrated circuits; tert-butyl(4-methylphenyl) ether is frequently used in biopharmaceutical β-properties. 2 The synthesis of amino acids.

[0003] Due to the presence of the tert-butyl group, it readily generates a tert-butyl carbocation, making conventional etherification reactions difficult to implement for this type of compound. Current reports on the synthesis of tert-butylphenyl ethers have several drawbacks. One method involves the catalytic preparation of tert-butylphenyl ether from isobutylene and phenol under strong acid conditions, but this method suffers from poor gas solubility, high equipment requirements, high energy consumption, and instability of tert-butylphenyl ether under acidic conditions. Another method involves the reaction of magnesium phenyl bromide with tert-butyl peroxide, but this method suffers from easy coupling of Grignard reagents, demanding reaction conditions, high exothermic reaction, and high risk. A third method involves coupling reactions using special catalysts such as cuprous oxide and palladium, but this method suffers from harsh environments caused by polar solvents and expensive catalysts. A fourth method involves the substitution reaction of tert-butyl halides with phenol to prepare tert-butylphenyl ether, but this method suffers from low yields and a tendency for side reactions.

[0004] To address the problems of complex preparation technology, high production cost, unstable product quality, and high requirements for reaction conditions for tert-butylphenyl ether, this invention provides a method for preparing tert-butylphenyl ether under mild conditions. This method has the advantages of simple synthesis process, mild reaction conditions, wide range of applications, short production cycle, and readily available raw materials. Summary of the Invention

[0005] This invention provides a method for preparing tert-butylphenyl ether and its derivatives, characterized in that di-tert-butyl dicarbonate is used as a raw material, and a metal catalyst is used to catalyze the synthesis of tert-butylphenyl ether and its derivatives.

[0006] The tert-butylphenyl ether and its derivatives have the structure shown in Formula I:

[0007] R1, R2, R3, R4, and R5 are each independently a different substituent group such as hydrogen, C1-C5 alkyl, alkoxy, or halogen;

[0008] The synthesis method includes the following steps: (1) adding aryl phenolic compounds and metal catalysts to an organic solvent, heating and then adding di-tert-butyl dicarbonate dropwise; (2) removing the solvent from the reaction material in step (1), and then extracting, washing, drying and other processes to obtain a high-purity product.

[0009] According to the present invention, the structure of the tert-butylphenyl ether and its derivatives includes:

[0010]

[0011]

[0012] According to the present invention, the organic solvents include: ethyl acetate, dichloromethane, acetone, tetrahydrofuran, dichloroethane, N,N-dimethylformamide, tert-butanol, etc., and are not limited to the solvents mentioned above, but include other similar solvents not mentioned.

[0013] According to the present invention, the metal catalyst in step (1) is composed of any of the following cations and any of the following anions, wherein the cations include Mg 2+ Zn 2+ Al 3+ In 3+ Cd 2+ ,Sc 2+ etc.; anions include Cl - SO4 - ClO4 - TfSO3 - wait.

[0014] According to the present invention, the molar ratio of arylphenol to metal catalyst in step (1) is 5-30, preferably 10-15.

[0015] According to the present invention, the molar ratio of ditert-butyl dicarbonate to arylphenol in step (1) is 2-4, preferably 2.5-3.

[0016] According to the present invention, the reaction temperature of the heating reaction in step (1) is 20-50°C and the reaction time is 1-6h; preferably the reaction temperature is 30-40°C and the reaction time is 2-4h.

[0017] According to the present invention, the temperature at which di-tert-butyl dicarbonate is added in step (1) is 20-50°C; preferably, the temperature at which di-tert-butyl dicarbonate is added is 30-40°C.

[0018] According to the present invention, a method for preparing tert-butylphenyl ether and its derivatives is provided. The method uses phenylphenol with different substituents as raw materials and activates di-tert-butyl dicarbonate with a metal catalyst to prepare tert-butylphenyl ether and its derivatives. The method specifically includes the following steps: (1) adding phenol and a metal catalyst to a non-polar solvent, and adding di-tert-butyl dicarbonate dropwise to the reactants at 30-40°C to prepare tert-butylphenyl ether; (2) removing the solvent after the reaction to obtain a crude product, and then extracting, washing, drying, etc. to obtain tert-butylphenyl ether with a purity ≥97%.

[0019] This method includes: adding phenylphenols with different substituents and a metal catalyst to an organic solvent; adding di-tert-butyl dicarbonate dropwise to the reactants at a reaction temperature to prepare tert-butylphenyl ethers with different substituents; after the reaction, removing the solvent to obtain a crude product, followed by extraction, washing, and drying to obtain high-purity tert-butylphenyl ethers and their derivatives. This invention provides a method for preparing tert-butylphenyl ethers and their derivatives. This method uses a metal catalyst to activate di-tert-butyl dicarbonate, followed by nucleophilic attack from phenol, and then removes two molecules of carbon dioxide to obtain tert-butylphenyl ethers. This overcomes the special conditions required by traditional methods involving tert-butyl bromide and isobutylene, and reduces reaction costs. Compared with existing technologies, this invention has the following technical advantages:

[0020] (1) Using di-tert-butyl dicarbonate as the tert-butyl source, the raw materials are readily available, the reaction conditions are mild, and the range of applicability is wide, making it more suitable for industrial production. (2) A special catalyst was used to prepare tert-butylphenyl ether from di-tert-butyl dicarbonate, which has high reactivity and wide applicability. (3) The post-processing in this method is simple, avoiding the use of highly polar solvents, and the reaction is easy to purify.

[0021] Analytical methods

[0022] In infrared characterization, solids were characterized using a KBr crystal slide as the background channel. After background subtraction, KBr and the sample were mixed thoroughly before slide preparation. The sample was then measured using an infrared spectrophotometer with a scanning range of 400–4000 cm⁻¹. -1 The liquid sample was analyzed using an infrared spectrophotometer with air as the background channel. After background subtraction, the sample was scanned within a range of 400–4000 cm⁻¹. -1 .

[0023] Nuclear magnetic resonance characterization was performed using deuterated chloroform as solvent and an AVABCEⅢHD 400 NMR instrument to detect the synthesized product by 1H-NMR.

[0024] The reaction solution was analyzed by gas chromatography using GL Scientific DB-1 (30m, 0.32um*0.25mm) as a filler. After holding at 80℃ for 5min, the temperature was increased to 200℃ at a rate of 15℃ / min for analysis. Attached Figure Description

[0025] Figure 1 tert-butylphenyl ether 1 H NMR spectrum

[0026] Figure 2 tert-butylphenyl ether 13 C NMR spectrum

[0027] Figure 3 IR spectrum of tert-butylphenyl ether Detailed Implementation

[0028] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions in the art or as recommended by the manufacturer. Any non-substantial changes and substitutions made by those skilled in the art based on the invention are within the scope of protection claimed by the present invention.

[0029] Example 1

[0030]

[0031] 9.40 g phenol (0.10 mol), 2.20 g magnesium perchlorate (0.01 mol), and 50 mL of dichloromethane solution were added to a 250 mL three-necked flask equipped with a reflux condenser and magnetic stirrer. After the reaction was heated to 40 °C, 43.6 g di-tert-butyl dicarbonate (0.20 mol) was added dropwise. After the addition was complete, the reaction was kept at this temperature for 4 h, and the phenol was observed to disappear by TLC.

[0032] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 10.7 g of tert-butoxybenzene, with a yield of 71.6%.

[0033] Comparative Example 1

[0034] 9.40 g phenol (0.10 mol), 0.95 g magnesium chloride (0.01 mol), and 50 mL of dichloromethane solution were added to a 250 mL three-necked flask equipped with a reflux condenser and magnetic stirrer. After the reaction temperature was raised to 40 °C, 43.6 g di-tert-butyl dicarbonate (0.20 mol) was added dropwise. After the addition was complete, the reaction was kept at this temperature for 4 h, and the phenol was observed to disappear by TLC.

[0035] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 5.7 g of tert-butoxybenzene, with a yield of 38.3%.

[0036] Comparative Example 2

[0037] Add 9.40g to a 250ml three-necked flask equipped with a reflux condenser and a magnetic stirrer.

[0038] After adding phenol (0.10 mol), 1.20 g magnesium sulfate (0.01 mol), and 50 mL of dichloromethane solution, the reaction was heated to 40 °C, and then 43.6 g di-tert-butyl dicarbonate (0.20 mol) was added dropwise. After the addition was complete, the reaction was kept at this temperature for 4 h, and the phenol was observed to disappear by TLC.

[0039] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 6.5 g of tert-butoxybenzene, with a yield of 43.5%.

[0040] Comparative Example 3

[0041] Add 9.40g to a 250ml three-necked flask equipped with a reflux condenser and a magnetic stirrer.

[0042] After adding phenol (0.10 mol), 3.72 g zinc perchlorate hexahydrate (0.01 mol), and 50 mL of dichloromethane solution, the reaction was heated to 40 °C, and then 43.6 g di-tert-butyl dicarbonate (0.20 mol) was added dropwise. After the addition was complete, the reaction was kept at this temperature for 4 h, and TLC monitoring showed that the phenol disappeared.

[0043] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 9.7 g of tert-butoxybenzene, with a yield of 65.5%.

[0044] Comparative Example 4

[0045] Add 9.40g to a 250ml three-necked flask equipped with a reflux condenser and a magnetic stirrer.

[0046] After adding phenol (0.10 mol), 3.22 g magnesium trifluoromethanesulfonate (0.01 mol), and 50 ml of dichloromethane solution, the reaction temperature was raised to 40 °C, and then 43.6 g di-tert-butyl dicarbonate (0.20 mol) was added dropwise. After the addition was complete, the reaction was kept at this temperature for 4 h, and the phenol was observed to disappear by TLC.

[0047] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 9.0 g of tert-butoxybenzene, with a yield of 60.3%.

[0048] Example 2

[0049]

[0050] 12.40 g of 3-methoxyphenol (0.1 mol), 3.31 g of magnesium perchlorate hexahydrate (0.01 mol), and 50 ml of dichloromethane solution were added to a 250 ml three-necked flask equipped with reflux condenser and magnetic stirrer. After the reaction temperature was raised to 40 °C, 43.6 g of di-tert-butyl dicarbonate (0.20 mol) was added dropwise. After the addition was complete, the reaction was kept at this temperature for 4 h. TLC monitoring showed that 3-methoxyphenol disappeared.

[0051] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 13.1 g of tert-butyl (3-methoxyphenyl) ether, with a yield of 73.0%.

[0052] Example 3

[0053]

[0054] 10.80 g of 2-methylphenol (0.1 mol), 3.31 g of magnesium perchlorate (0.01 mol), and 50 ml of dichloromethane solution were added to a 250 ml three-necked flask equipped with reflux condenser and magnetic stirrer. After the reaction temperature was raised to 40 °C, 43.6 g of di-tert-butyl dicarbonate (0.20 mol) was added dropwise. After the addition was complete, the reaction was kept at this temperature for 4 h. TLC monitoring showed that 2-methylphenol disappeared.

[0055] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 11.9 g of tert-butyl (4-methylphenyl) ether, with a yield of 66.0%.

[0056] Example 4

[0057]

[0058] 13.90 g of 4-nitrophenol (0.1 mol), 3.72 g of zinc perchlorate hexahydrate (0.01 mol), and 50 ml of dichloromethane solution were added to a 250 ml three-necked flask equipped with reflux condenser and magnetic stirrer. After the reaction temperature was raised to 40 °C, 43.6 g of di-tert-butyl dicarbonate (0.20 mol) was added dropwise. After the addition was complete, the reaction was kept at this temperature for 4 h. TLC monitoring showed that 4-nitrophenol disappeared.

[0059] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 11.00 g of tert-butyl (4-nitrophenyl) ether, with a yield of 56.3%.

[0060] Example 5

[0061]

[0062] 13.90 g of 3-fluorophenol (0.1 mol), 3.22 g of magnesium trifluoromethanesulfonate (0.01 mol), and 50 ml of dichloromethane solution were added to a 250 ml three-necked flask equipped with reflux condenser and magnetic stirrer. After the reaction temperature was raised to 40 °C, 43.6 g of di-tert-butyl dicarbonate (0.20 mol) was added dropwise. After the addition was complete, the reaction was kept at this temperature for 4 h. TLC monitoring showed that 3-fluorophenol disappeared.

[0063] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 9.40 g of tert-butyl (3-fluorophenyl) ether, with a yield of 56.1%.

[0064] Example 6

[0065]

[0066] To a 250 ml three-necked flask equipped with a reflux condenser and magnetic stirrer, add 13.90 g of 4-cyanobenzylphenol (0.1 mol), 3.22 g of magnesium trifluoromethanesulfonate (0.01 mol), and 50 ml of dichloromethane solution. After heating the reaction to 40 °C, add 43.6 g of di-tert-butyl dicarbonate (0.20 mol) dropwise. After the addition is complete, maintain the reaction temperature for 4 h. TLC monitoring shows that 4-cyanobenzylphenol disappears.

[0067] Post-processing: After the reaction was completed, the mixture was cooled to room temperature, and 100 ml of water was added to dilute the reaction solution. The organic phase was separated and extracted multiple times with dichloromethane. The organic phase was dried and the solvent was evaporated to obtain 9.40 g of tert-butyl (4-cyanobenzyl) ether, with a yield of 51.8%.

Claims

1. A method for preparing tert-butylphenyl ether and its derivatives, characterized in that, Using di-tert-butyl dicarbonate as a raw material, tert-butylphenyl ether and its derivatives were synthesized by catalysis with a metal catalyst. The tert-butylphenyl ether and its derivatives have the structure shown in Formula I: R1, R2, R3, R4, and R5 are each independently a different substituent group such as hydrogen, C1-C5 alkyl, alkoxy, or halogen. The synthesis method includes the following steps: (1) adding aryl phenolic compounds and metal catalysts to an organic solvent, heating and then adding di-tert-butyl dicarbonate dropwise; (2) removing the solvent from the reaction material in step (1), and then extracting, washing, drying and other processes to obtain a high-purity product.

2. The preparation method according to claim 1, wherein the structure of the tert-butylphenyl ether and its derivatives comprises:

3. The preparation method according to claim 1, wherein the organic solvent comprises: Organic solvents such as ethyl acetate, dichloromethane, acetone, tetrahydrofuran, dichloroethane, N,N-dimethylformamide, and tert-butanol, and not only those mentioned above, but also other similar solvents not mentioned.

4. The preparation method according to claim 1, wherein the metal catalyst in step (1) is composed of any of the following cations and any of the following anions, the cations including Mg 2+ Zn 2+ Al 3+ In 3+ Cd 2+ ,Sc 2+ etc.; anions include Cl - SO4 - ClO4 - TfSO3 - wait.

5. According to the preparation method of claim 1, the molar ratio of arylphenol to metal catalyst in step (1) is 5-30, preferably 10-15.

6. According to the preparation method of claim 1, the molar ratio of ditert-butyl dicarbonate to arylphenol in step (1) is 2-4, preferably 2.5-3.

7. According to the preparation method of claim 1, the reaction temperature of the heating reaction in step (1) is 20-50℃ and the reaction time is 1-6h; preferably the reaction temperature is 30-40℃ and the reaction time is 2-4h.

8. According to the preparation method of claim 1, the temperature at which di-tert-butyl dicarbonate is added dropwise in step (1) is 20-50°C; preferably, the temperature at which di-tert-butyl dicarbonate is added dropwise is 30-40°C.

9. According to claims 1-8, a method for preparing tert-butylphenyl ether and its derivatives, the method using phenylphenol with different substituents as raw materials, activating di-tert-butyl dicarbonate with a metal catalyst to prepare tert-butylphenyl ether and its derivatives, specifically including the following steps: (1) adding phenol and a metal catalyst to a non-polar solvent, and adding di-tert-butyl dicarbonate dropwise to the reactants at 30-40°C to prepare tert-butylphenyl ether; (2) removing the solvent after the reaction to obtain a crude product, and then extracting, washing, drying, etc. to obtain tert-butylphenyl ether with a purity ≥97%.

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