Triphosgene: an efficient chlorination reagent for synthesis of 5-chloro-2-pentanone from acetyl-n-propanol

Abstract

Abstract 5-Chloro-2-pentanone (5C2P) and its derivatives are widely utilized in the pharmaceutical and agrochemical industry. A new catalytic approach was proposed to convert acetyl-n-propanol to 5C2P using bis(trichloromethyl)carbonate (triphosgene, BTC) as the efficient chlorine source. Various qualitative and quantitative nuclear magnetic resonance techniques (1H, 13C NMR) especially 1D selective gradient total correlation spectroscopy (Sel-TOCSY) and 2D heteronuclear single quantum correlation (1H-13C HSQC) were used in the process. The reaction conditions, such as temperature, time, mole ratio, solvent as well as initiator were optimized. Experiment results showed that the yield of 5C2P reached a maximum of 97.93% in 1,2-dichloroethane at 80°C after 2 h under the initiation of N,N-dimethylacetamide (DMAC), and the optimal molar ratio of acetyl-n-propanol to BTC was 1:0.4. The reaction mechanism was proposed and confirmed accordingly. Interestingly, an intermediate product of 1-(dimethylamino)ethyl carbonochloridate was observed and its chemical structure was characterized by both Sel-TOCSY and 1H-13C HSQC. This study enriched the catalytic reaction ways for the preparation of 5C2P.