| 92% |
With sulfuryl dichloride; sodium hydroxide In dichloromethane at 22℃; for 6.5h; |
1.1; 2.1; 3.1 Example 3
1. Add 12.40g (0.10mol) of guaiacol, 0.18mol of thionyl chloride and 80ml of dichloroethane into a 200ml round-bottom flask, stir the reaction at 22°C, and absorb the tail gas with sodium hydroxide solution. After 6.5 hours of reaction, heating was stopped, saturated sodium bicarbonate solution was added to the reaction mixture to neutralize to pH=6-7, and the dichloroethane layer was separated, dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to remove dichloroethane. 14.59 g of 4-chloro-2-methoxyphenol was obtained with a yield of 92%. |
| 87% |
With N-chloro-succinimide In various solvent(s) at 27℃; for 0.75h; |
|
| 80% |
With sulfuryl dichloride In chloroform at -5 - 60℃; for 24h; Inert atmosphere; |
2.2.1 2.1 Preparation of 4-chloroguaiacol
In an argon-protected ice salt bath (-5°C), guaiacol (12.4 g, 100 mmol) was uniformly dispersed with 50 mL of chloroform, and sulfonyl chloride (13 mL, 160 mmol) was slowly dropped into it.After the dripping is completed, move to 60°C and reflux the reaction for 24 hours, and monitor the reaction by TLC spot plate.Under ice bath, thereaction was quenchedwith 50mL Sat.Na2S2O3solution, separated in a separatory funnel, the aqueous layer was extracted 3 times with chloroform, and the organic phases were combined and backwashed with saturated brine once. After drying with sodium sulfate and spin-drying, 16.7 g of crude brown liquid was obtained.After vacuum distillation (82-90°C/2mmHg, lit.130°C/7.5mmHg), a pale yellow oily liquid 4-chloroguaiacol (12.7g, 80%) with a content of 87% (GC-MS) was obtained. |
| 80% |
With sulfuryl dichloride at -5 - 60℃; for 24h; Inert atmosphere; |
5 Example 5 Preparation of 4-chloroguaiacol
Under an argon-protected ice-salt bath (-5°C), guaiacol (12.4 g, 100 mmol) was uniformly dispersed in 50 mL of chloroform,Sulfonyl chloride (13 mL, 160 mmol) was slowly added dropwise thereto. After the dripping was completed, it was moved to 60°C for reflux reaction for 24h, and the reaction was monitored by TLC spot plate.Under ice bath, the reaction was quenched with 50 mL of Sat.Na2S2O3 solution, and the liquid was separated in a separating funnel, and the aqueous layer was extracted with chloroform three times.The organic phases were combined, backwashed once with saturated brine, dried over anhydrous sodium sulfate, and spin-dried to obtain 16.7 g of a crude brownish-yellow liquid.After distillation under reduced pressure (82-90°C/2mmHg, lit.130°C/7.5mmHg), a pale yellow oily liquid 4-chloroguaiacol (12.7g, 80%) was obtained,Content 87% (GC-MS). |
| 77% |
With sulfuryl dichloride In chloroform at 35℃; |
|
| 43% |
With sulfuryl dichloride In chloroform at 0 - 60℃; for 15h; Inert atmosphere; |
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With oxygen; lithium chloride; copper dichloride In acetic acid at 60℃; for 7h; |
|
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With sulfuryl dichloride; sodium carbonate In water; toluene |
1 1st Reaction Step
EXAMPLE 1 1st Reaction Step 124 g of o-methoxyphenol and 200 ml of dry toluene are placed in a four-necked flask fitted with stirrer, condenser and dropping funnel. 148 g of sulfuryl chloride are added dropwise, with stirring, over about 1 hour, the temperature of the reaction mixture being kept at 20 to 25° C. After the addition is complete, stirring is continued at room temperature for 2 hours, after which time the reaction mixture is transferred to a separating funnel, shaken with 50 ml portions of 5% sodium carbonate solution, washed with 50 ml of water and dried over sodium sulfate. Subsequently, the sodium sulfate is removed by filtration and the chlorinated reaction product is subjected to distillation under reduced pressure. This yields 144 g of 2-methoxy-4-chlorphenol having a melting point of 128 to 134° C. at 1999.8 Pa Hg. |
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With hydrogenchloride; oxygen; copper dichloride In water at 50℃; for 0.333333h; Microwave irradiation; |
2.1. General Methods
General procedure: Phenols (78mmol) and a catalytic amount of CuCl2 (7.8mmol) were dissolved in 100mL of aqueous hydrochloric acid solution (6mol/L), and the mixture was bubbled with dioxygen (22 mL/min). The reaction was performed on a microreactor at 50 °C and measured by gas chromatography (GC). After GC showed the disappearance of the starting material, the reaction was extracted with dichloromethane (100mL × 2), and the organic layer was washed with water (50mL × 2) and fractionated to give the desired product. |
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