Shenzhen Zinwi Bio-tech Co., Ltd

Weixian Luo

Yang Zou

Jun Zou

Meisen Liu

The present application provides a preparation method of racemic nicotine, including the following steps: Nicotinyl chloride and methylamine are reacted under alkaline conditions to obtain methylnicotinamide, then condensed with monochloroacetone to obtain N-methyl-N-(2-oxopropyl) nicotinamide, then self-aldol condensed to obtain 1-methyl-5-(pyridin-3-yl)-1,2-dihydro-3H-pyrrol-3-one, and finally reduced to obtain racemic nicotine.

Preparation method of racemic nicotine

A method for preparing chiral synthetic nicotine includes the following steps: Step S1. condensing nicotinic acid ester and γ-butyrolactone under the action of alkaline condensate in organic solvent I to obtain the first mixture; Step S2. performing a ring-opening reaction to the first mixture obtained in Step S1 by adding an acidic substance to obtain a second mixture; Step S3. separating 4-chloro-1-(3-pyridine)-1-butanone from the second mixture obtained in Step S2, reacting with chiral tert-butyl sulfinamide to obtain chiral N-(4-chloro-1-(pyridin-3-yl)butene)-2-methylpropane-2-sulfinamide; Step S4: reacting the chiral N-(4-chloro-1-(pyridin-3-yl) butene)-2-methylpropane-2-sulfenamide with a reducing agent, and then cyclizing under the action of hydrogen halide to obtain a chiral demethylized nicotine; and Step S5: performing methylamination to the chiral demethylized nicotine to obtain a chiral nicotine.

Method for preparing chiral synthetic nicotine

The present application discloses a synthesis method of chiral nicotine from nicotinate and γ-butyrolactone, including the following steps: Step S1: performing condensation under an alkaline condition, and performing ring opening reaction with hydrochloric acid; Step S2: reacting with (+)—B-diisopinocampheyl chloroborane to produce a chiral hydroxyl group; Step S3: performing a chlorination reaction; and Step S4: performing cyclization under an alkaline condition to obtain the chiral nicotine. In the present application, nicotinate and γ-butyrolactone, both cheap and readily available, are used as raw materials, so as to reduce the production cost of (S)-nicotine. (+)—B-diisopinocampheyl chloroborane is used to reduce a carbonyl group of an intermediate to obtain a target chiral center. The (+)—B-diisopinocampheyl chloroborane induces the production of a chiral hydroxyl group, chlorination and cyclization are performed to form chiral (S)-demethylnicotine, and finally amine methylation is performed to obtain (S)-nicotine with photochemical activity.

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Guangdong, China

Weixian Luo