Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids via Hydrogen Atom Transfer
Wen-Yun Tan, Yi Lu, Jing-Feng Zhao, Wen Chen and Hongbin Zhang*
*School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, People's Republic of China,
Email: zhanghb
ynu.edu.cn
W.-Y. Tan, Y. Lu, J.-F. Zhao, W. Chen, H. Zhang, Org. Lett., 2021, 23, 6648-6653.
DOI: 10.1021/acs.orglett.1c02188
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Abstract
A metal-free, chemoselective oxidation of primary alcohols and aldehydes with cheap 1-hydroxycyclohexyl phenyl ketone as oxidant to the corresponding carboxylic acids features an easy to handle procedure, high isolated yields, and good to excellent functional group tolerance even in the presence of vulnerable secondary alcohols and tert-butanesulfinamides.
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Proposed Pathyway for 1-HCPK-Mediated Oxidations and Recycling of 1-HCPK
General procedure for the oxidation of primary alcohols
An 8 mL flask equipped with a magnetic stirbar was charged with alcohols (1.0
mmol), 1-Hydroxycyclohexyl phenyl ketone (408.5 mg, 2.0 mmol), sodium hydroxide
(80.0 mg, 2.0 mmol) and
1,2-dimethoxyethane (DME, 1.5 mL). The flask was then sealed with a cap and the
reaction mixture was allowed to stir at 80°C. The reaction progress was
monitored by TLC until no starting material was observed. The reaction mixture
was then cooled to room temperature, and was ready for work-up and purification
either through Method A or Method B, unless otherwise indicated.
General procedure for the oxidation of aldehydes
An 8 mL flask equipped with a magnetic stirbar was charged with aldehydes (1.0 mmol), 1-Hydroxycyclohexyl phenyl ketone (204.3 mg, 1.0 mmol), sodium hydroxide (80.0 mg, 2.0 mmol) and DME (1.5 mL). The flask was then sealed with a cap, and the reaction mixture was allowed to stir at 80°C. The reaction progress was monitored by TLC until no starting material was observed. The reaction mixture was then cooled to room temperature, and was ready for work-up and purification either using Method A or Method B, unless otherwise indicated.
General procedures for work-up and purification
Method A: The cooled reaction mixture was diluted with water (30 mL). The resulting mixture was then extracted with diethyl ether (3 × 20 mL) to remove 1-(hydroxy(phenyl)methyl)cyclohexanol and DME before acidification. The aqueous layer was then neutralized with 12 N HCl (166.7 µL, 2.0 mmol), and extracted with ethyl acetate (3 × 20 mL). The combined organic phases were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (Petroleum ether : EtOAc = 5 :1 → EtOAc : MeOH = 10 : 1) to afford pure carboxylic acids.
Method B: The cooled reaction mixture was diluted with water (30 mL). The resulting mixture was then extracted with diethyl ether (3 × 20 mL) to remove 1-(hydroxy(phenyl)methyl)cyclohexanol and DME before acidification. Then macroporous weakly acid cation exchange resin (ca. 5.0 g) was added to the aqueous layer. The resulting mixture was stirred until neutralization was completed. The mixture was filtered and washed with MeOH (25 mL). The filtrate was concentrated. The residue was purified by flash chromatography (Petroleum ether : EtOAc = 5 :1 → EtOAc : MeOH = 10 : 1) to afford pure carboxylic acids.
Key Words
1-hydroxycyclohexyl phenyl ketone, Oppenauer Oxidation, oxidiation of alcohols, oxidation of aldehydes
ID: J54-Y2021
