High-stereoselectivity method for synthesizing menthyl halide

A technology of stereoselectivity and synthetic method, which is applied to the preparation of halogenated hydrocarbons, chemical instruments and methods, organic chemistry, etc., can solve the problems of harsh reaction conditions, complicated methods, and no de value given, and achieve high selectivity, The effect of simple preparation method

Active Publication Date: 2013-04-03
ANHUI PROVINCE YIFAN SPICE
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Problems solved by technology

[0003] The Lepore research group (Angew.Chem., Int.Ed.2008, 47, 7511) first made L-menthol into L-menthol sulfonate, through TiBr 4 Bromination reaction is carried out, and the main product is menthyl bromide. This method is relatively complicated and the reaction conditions are harsh (performed at -78°C), but the de value is not given, and only the optical rotation value is used to illustrate the purity of the product.
Yamashita et al. (Bull.Cem.Soc.Jpn.1983,56,219) used HBr-H 2 SO 4 Carry out the bromination reaction of menthol, although the synthesis method is simple, but the de value is not high

Method used

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  • High-stereoselectivity method for synthesizing menthyl halide

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Experimental program
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Embodiment 1

[0022] Under nitrogen protection, add 15mmol of L-menthol and 20mL of anhydrous ether to a 50mL three-necked flask, slowly add 5mmol of phosphorus tribromide dropwise to the three-necked flask under ice bath, control the rate of addition, so that the reaction temperature is not higher than 5 ℃, after the dropwise addition, react at 0℃ for 2h, then raise the temperature to 25℃ for reaction, TLC detects the reaction end point, add saturated aqueous sodium carbonate solution, separate the organic layer, extract the aqueous layer with ether three times, and wash three times with water, and anhydrous MgS0 4 Drying, separation by column chromatography (eluent volume ratio n-hexane:ethyl acetate=20:1) yielded 2.81 g of the target product, neomenthyl bromide, with a yield of 85.4%. 1 HNMR detection de>99%.

[0023] 1 H NMR (CDCl 3 , 400MHz) δ: 4.67 (m, 1H, CBrH), 2.14-2.19 (m, 1H), 1.72-1.77 (m, 2H), 1.32-1.54 (m, 5H), 0.74-0.67 (m, 10H).

Embodiment 2

[0025] Under nitrogen protection, add 15mmol of L-menthol and 20mL of anhydrous ether to a 50mL three-necked flask, slowly add 10mmol of phosphorus tribromide to the three-necked flask under ice bath, and control the rate of addition so that the reaction temperature is not higher than 5 ℃, after the dropwise addition, react at 0℃ for 2h, then raise the temperature to 25℃ for reaction, TLC detects the reaction end point, add saturated aqueous sodium carbonate solution, separate the organic layer, extract the aqueous layer with ether three times, and wash three times with water, and anhydrous MgS0 4 Drying, separation by column chromatography (eluent volume ratio n-hexane:ethyl acetate=20:1) yielded 2.98g of the target product, neomenthyl bromide, with a yield of 90.6%. 1 HNMR detection de>99%.

[0026] 1 H NMR (CDCl 3 , 400MHz) δ: 4.67 (m, 1H, CBrH), 2.14-2.19 (m, 1H), 1.72-1.77 (m, 2H), 1.32-1.54 (m, 5H), 0.74-0.67 (m, 10H).

Embodiment 3

[0028] Under the protection of nitrogen, add 15mmol of L-menthol and 20mL of anhydrous ether to a 50mL three-necked flask, slowly add 15mmol of phosphorus tribromide to the three-necked flask under ice bath, and control the rate of addition so that the reaction temperature is not higher than 5 ℃, after the dropwise addition, react at 0℃ for 2h, then raise the temperature to 25℃ for reaction, TLC detects the reaction end point, add saturated aqueous sodium carbonate solution, separate the organic layer, extract the aqueous layer with ether three times, and wash three times with water, and anhydrous MgS0 4 Drying and separation by column chromatography (eluent volume ratio n-hexane:ethyl acetate=20:1) yielded 3.01 g of the target product, neomenthyl bromide, with a yield of 91.5%. 1 HNMR detection de>99%.

[0029] 1 HNMR (CDCl 3 , 400MHz) δ: 4.67 (m, 1H, CBrH), 2.14-2.19 (m, 1H), 1.72-1.77 (m, 2H), 1.32-1.54 (m, 5H), 0.74-0.67 (m, 10H).

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Abstract

The invention discloses a high-stereoselectivity method for synthesizing menthyl halide, which comprises the following steps: adding menthol into a solvent in a nitrogen protective atmosphere, and dropwisely adding phosphorus tribromide or phosphorus trichloride in an ice bath, wherein the dropwise addition speed is controlled so that the reaction temperature is not higher than 5 DEG C; and after the dropwise addition, reacting at 0 DEG C for 2 hours, heating to 25 DEG C to react, detecting the reaction end point by TLC (thin layer chromatography), separating, washing, and drying to obtain the target product. The menthyl halide prepared by the method disclosed by the invention has the advantages of high yield and extremely high stereoselectivity, and the de value is greater than 99%.

Description

1. Technical field [0001] The present invention mainly relates to an asymmetric synthesis method, in particular to a method for synthesizing menthyl halides with high stereoselectivity. 2. Background technology [0002] Menthyl halide is an important organic intermediate, mainly referring to menthyl bromide or menthyl chloride, because bromine atom or chlorine atom is easily converted into other functional groups, so menthyl bromide or menthyl chloride is an excellent chiral source, many chiral intermediates and chiral catalysts with menthyl groups can be synthesized. [0003] The Lepore research group (Angew.Chem., Int.Ed.2008, 47, 7511) first made L-menthol into L-menthol sulfonate, through TiBr 4 The bromination reaction produces menthyl bromide as the main product. This method is relatively complicated and the reaction conditions are harsh (performed at -78°C), but the de value is not given, and only the optical rotation value is used to illustrate the purity of the pro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C17/16C07C23/10
Inventor 李天赋祝飞钟琦
Owner ANHUI PROVINCE YIFAN SPICE
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