Method for synthesizing 4-(4-phenylbutoxy) benzoic acid

Abstract

The invention discloses a method for synthesizing 4-(4-phenylbutoxy) benzoic acid and belongs to the technical field of organic synthesis. According to the method, 4-chlorine-1-butanol serves as the raw material, four steps of reactions are conducted to synthesize the 4-(4-phenylbutoxy) benzoic acid, ferrous sulfate, lithium chloride and manganese chloride are added in the first step, the second step and the third step respectively and serve as catalysts, the reaction condition is optimized, use of poisonous and harmful solvent is reduced, and reaction efficiency is improved; reaction energy consumption is lowered, or reaction time is shortened, high economic benefits are achieved, meanwhile, subsequent disposal of the catalysts is simple, the catalysts can be separated by separating a water layer, the method is beneficial to industrialized popularization, and high economic benefits are achieved.

Description

Technical field:

[0001] The invention relates to a synthesis method of p-phenylbutoxybenzoic acid, which belongs to the field of chemical synthesis. Background technique:

[0002] p-Phenylbutoxybenzoic acid is also called p-phenylbutoxybenzoic acid or 4-(4-phenylbutoxy)benzoic acid. It is in the shape of white crystals, almost insoluble in water, but soluble in organic solvents such as ethanol. p-Phenylbutoxybenzoic acid is the main intermediate in the synthesis of pranlukast, and it reacts with 8-amino-4-oxo-2-(5-1H-tetrazole)-4H-1-benzopyran in two In the methyl chloride system, pyridine is used as an acid-binding agent, and Prankast is acylated. At present, the research and development of prankast has a broad market prospect, so the research on p-phenylbutoxybenzoic acid is also of great significance.

[0003] In the prior art, for the synthesis of p-phenylbutoxybenzoic acid mainly by the following methods:

[0004] Using tetrahydrofuran as raw material, p-phenylbutoxy...

Examples

Embodiment 1

[0074] A synthetic method for p-phenylbutoxybenzoic acid, comprising the following steps:

[0075] The first step: Synthesis of 4-phenyl-1-butanol:

[0076] Put 40g of benzene into a dry reaction bottle, add 2g of ferrous sulfate, stir and heat, control the temperature at 10°C, add 20g of 4-chloro-1-butanol dropwise, and keep at 18-19°C after the dropwise addition Temperature reaction for 1.5h;

[0077] After the reaction was completed, the temperature was slowly lowered to room temperature, 100 g of saturated sodium sulfate aqueous solution was added, and the layers were separated, and the organic layer was collected for debenzene removal under reduced pressure, and dried to obtain 4-phenyl-1-butanol;

[0078] The second step: Synthesis of 4-phenylbutoxysulfonate:

[0079] Add 80g of acetonitrile solution, 1g of lithium chloride and 4-phenyl-1-butanol synthesized in the first step to the dry reaction flask, stir and mix slowly, cool to 5°C and keep the temperature constant,...

Embodiment 2

[0087] A synthetic method for p-phenylbutoxybenzoic acid, comprising the following steps:

[0088] The first step: Synthesis of 4-phenyl-1-butanol:

[0089] Put 40g of benzene into a dry reaction flask, add 3g of ferrous sulfate, stir and heat, control the temperature at 17°C, add 20g of 4-chloro-1-butanol dropwise, and keep the temperature at 20°C for reaction 1.5h;

[0090] After the reaction was completed, the temperature was slowly lowered to room temperature, 100 g of saturated sodium sulfate aqueous solution was added, and the layers were separated, and the organic layer was collected for debenzene removal under reduced pressure, and dried to obtain 4-phenyl-1-butanol;

[0091] The second step: Synthesis of 4-phenylbutoxysulfonate:

[0092] Add 80g of acetonitrile solution, 2g of lithium chloride and 4-phenyl-1-butanol synthesized in the first step to the dry reaction flask, stir and mix slowly, cool to 8°C and keep the temperature constant, add 8.8g of methyl Sulfony...

Embodiment 3

[0100] A synthetic method for p-phenylbutoxybenzoic acid, comprising the following steps:

[0101] The first step: Synthesis of 4-phenyl-1-butanol:

[0102] Put 40g of benzene into a dry reaction bottle, add 3g of ferrous sulfate, stir and heat, control the temperature at 10°C, add 20g of 4-chloro-1-butanol dropwise, and keep the temperature at 20°C for reaction 1.5h;

[0103] After the reaction was completed, the temperature was slowly lowered to room temperature, 100 g of saturated sodium sulfate aqueous solution was added, and the layers were separated, and the organic layer was collected for debenzene removal under reduced pressure, and dried to obtain 4-phenyl-1-butanol;

[0104] The second step: Synthesis of 4-phenylbutoxysulfonate:

[0105] Add 80g of acetonitrile solution, 1g of lithium chloride and 4-phenyl-1-butanol synthesized in the first step to the dry reaction flask, stir and mix slowly, cool to 5°C and keep the temperature constant, add 8.8g of methyl Sulfonyl...

Technical field:

[0001] The invention relates to a synthesis method of p-phenylbutoxybenzoic acid, which belongs to the field of chemical synthesis. Background technique:

[0002] p-Phenylbutoxybenzoic acid is also called p-phenylbutoxybenzoic acid or 4-(4-phenylbutoxy)benzoic acid. It is in the shape of white crystals, almost insoluble in water, but soluble in organic solvents such as ethanol. p-Phenylbutoxybenzoic acid is the main intermediate in the synthesis of pranlukast, and it reacts with 8-amino-4-oxo-2-(5-1H-tetrazole)-4H-1-benzopyran in two In the methyl chloride system, pyridine is used as an acid-binding agent, and Prankast is acylated. At present, the research and development of prankast has a broad market prospect, so the research on p-phenylbutoxybenzoic acid is also of great significance.

[0003] In the prior art, for the synthesis of p-phenylbutoxybenzoic acid mainly by the following methods:

[0004] Using tetrahydrofuran as raw material, p-phenylbutoxy...

Examples

Embodiment 1

[0074] A synthetic method for p-phenylbutoxybenzoic acid, comprising the following steps:

[0075] The first step: Synthesis of 4-phenyl-1-butanol:

[0076] Put 40g of benzene into a dry reaction bottle, add 2g of ferrous sulfate, stir and heat, control the temperature at 10°C, add 20g of 4-chloro-1-butanol dropwise, and keep at 18-19°C after the dropwise addition Temperature reaction for 1.5h;

[0077] After the reaction was completed, the temperature was slowly lowered to room temperature, 100 g of saturated sodium sulfate aqueous solution was added, and the layers were separated, and the organic layer was collected for debenzene removal under reduced pressure, and dried to obtain 4-phenyl-1-butanol;

[0078] The second step: Synthesis of 4-phenylbutoxysulfonate:

[0079] Add 80g of acetonitrile solution, 1g of lithium chloride and 4-phenyl-1-butanol synthesized in the first step to the dry reaction flask, stir and mix slowly, cool to 5°C and keep the temperature constant,...

Embodiment 2

[0087] A synthetic method for p-phenylbutoxybenzoic acid, comprising the following steps:

[0088] The first step: Synthesis of 4-phenyl-1-butanol:

[0089] Put 40g of benzene into a dry reaction flask, add 3g of ferrous sulfate, stir and heat, control the temperature at 17°C, add 20g of 4-chloro-1-butanol dropwise, and keep the temperature at 20°C for reaction 1.5h;

[0090] After the reaction was completed, the temperature was slowly lowered to room temperature, 100 g of saturated sodium sulfate aqueous solution was added, and the layers were separated, and the organic layer was collected for debenzene removal under reduced pressure, and dried to obtain 4-phenyl-1-butanol;

[0091] The second step: Synthesis of 4-phenylbutoxysulfonate:

[0092] Add 80g of acetonitrile solution, 2g of lithium chloride and 4-phenyl-1-butanol synthesized in the first step to the dry reaction flask, stir and mix slowly, cool to 8°C and keep the temperature constant, add 8.8g of methyl Sulfony...

Embodiment 3

[0100] A synthetic method for p-phenylbutoxybenzoic acid, comprising the following steps:

[0101] The first step: Synthesis of 4-phenyl-1-butanol:

[0102] Put 40g of benzene into a dry reaction bottle, add 3g of ferrous sulfate, stir and heat, control the temperature at 10°C, add 20g of 4-chloro-1-butanol dropwise, and keep the temperature at 20°C for reaction 1.5h;

[0103] After the reaction was completed, the temperature was slowly lowered to room temperature, 100 g of saturated sodium sulfate aqueous solution was added, and the layers were separated, and the organic layer was collected for debenzene removal under reduced pressure, and dried to obtain 4-phenyl-1-butanol;

[0104] The second step: Synthesis of 4-phenylbutoxysulfonate:

[0105] Add 80g of acetonitrile solution, 1g of lithium chloride and 4-phenyl-1-butanol synthesized in the first step to the dry reaction flask, stir and mix slowly, cool to 5°C and keep the temperature constant, add 8.8g of methyl Sulfonyl...

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