Preparation of 6-Bromocaproic Acid

6-bromohexanoic acid, also called 6-bromohexanoic acid or 6-bromo-hexanoic acid, is an organobromine compound comprising hexanoic acid having a bromo substituent at the 6-position [1]. 6-Bromohexanoic acid is used in the preparation of N-acylsulfonamides, diarylthioethers and 2-lithio-1,3-dithian. It is widely used as an intermediate in organic synthesis [2]. Here, we introduced a method for making this compound. 

The method of preparing a high-purity 6-bromo-hexanoic acid proposed by the present invention, comprises the following steps: dry hydrogen bromide gas directly into the organic solvent containing ε- caprolactone, a dry hydrogen bromide on the amount of ε - caprolactone 1.0-2.0 fold (molar ratio); stirring, ring-opening reaction, the reaction temperature is 0 ℃ ~ 100 ℃, generating a high-purity 6-bromo-hexanoic acid.

The present invention is further specifically described below by way of examples.

Example 1: A 500 ml three-necked flask, a thermometer, a stirrer, a raw material was added ε- caprolactone (1 mol, 114 g), n-hexane (200 mL), and then stirring was started. Leads to dry hydrogen bromide gas (1.1 moles, 89 g), controlling the reaction temperature is 20 ℃ ~ 30 ℃. After hydrogen bromide gas introduced into the end, and then stirred at this temperature for 6 hours. Then cooled to 0 ~ 10 ℃, stirred for 3 hours, large crystals. Filtered to give 6-bromo-hexanoic acid as a pale yellow solid weighing 183 g, yield 95%, purity 99.2% (gas chromatograph analysis).

Example 2: A 500 ml three-necked flask, a thermometer, a stirrer, a raw material was added ε- caprolactone (1 mol, 114 g), cyclohexane (150 ml), then stirring was started. Leads to dry hydrogen bromide gas (1.2 moles, 97 g), controlling the reaction temperature is 30 ℃ ~ 40 ℃. After hydrogen bromide gas introduced into the end, and then stirred at this temperature for 5 hours. Then cooled to 5 ~ 15 ℃, stirred for 2 hours, large crystals. Filtered to give 6-bromo-hexanoic acid as a pale yellow solid weighing 180 g, yield 92%, purity 99.4% (gas chromatograph analysis).

Example 3: 500 ml three necked flask, a thermometer, a stirrer, a raw material was added ε- caprolactone (1 mol, 114 g), toluene (200 mL), and then stirring was started. Leads to dry hydrogen bromide gas (1.3 moles, 105 g), controlling the reaction temperature is 40 ℃ ~ 50 ℃. After hydrogen bromide gas introduced into the end, and then stirred at this temperature for 4 hours. Then cooled to 10 ~ 20 ℃, stirred for 4 hours, large crystals. Filtered to give 6-bromo-hexanoic acid as a pale yellow solid weighing 185 g, yield 95%, purity 99.1% (gas chromatograph analysis).

Example 4: A 500 ml three-necked flask, a thermometer, a stirrer, a raw material was added ε- caprolactone (1 mol, 114 g), methylene chloride (200 mL), and then stirring was started. Leads to dry hydrogen bromide gas (1.8 moles, 146 g), controlling the reaction temperature is 0 ℃ ~ 20 ℃. After hydrogen bromide gas introduced into the end, and then stirred at this temperature for 7 hours. Then dichloromethane was distilled at atmospheric pressure, followed by addition of n-hexane (200 mL), cooled to -5 ~ 10 ℃, stirred for 5 hours, large crystals. Filtered to give 6-bromo-hexanoic acid as a pale yellow solid weighing 181 g, yield 93%, purity 99.2% (gas chromatograph analysis).

Reference

[1] https://pubchem.ncbi.nlm.nih.gov/compound/6-Bromohexanoic-acid
[2] https://www.alfa.com/zh-cn/catalog/A15761/
[3] https://patents.glgoo.top/patent/CN1865218A/en?q=CN1865218