Preparation method for 3-aminomethyltetrahydrofuran

Abstract

The invention discloses a preparation method for 3-aminomethyltetrahydrofuran. The preparation method comprises the following steps: with acrylonitrile as a starting material, carrying out an addition reaction with 2-halogenated ethyl alcohol so as to obtain an intermediate 2-haloethyl-2-nitrile ethyl ether; then subjecting the intermediate 2-haloethyl-2-nitrile ethyl ether to cyclic condensation so as to obtain an intermediate 3-nitrile tetrahydrofuran; and finally subjecting the intermediate 3-nitrile tetrahydrofuran to catalytic hydrogenation so as to obtain 3-aminomethyltetrahydrofuran. The preparation method provided by the invention has the advantages of cheap and easily-available starting material, short synthetic route, simple process operation, low production cost, little pollution to the human body and the environment, good yield and applicability to large-scale industrial production.

Description

technical field

[0001] The invention belongs to the technical field of fine chemical synthesis, and in particular relates to a preparation method of 3-aminomethyltetrahydrofuran. Background technique

[0002] 3-Aminomethyltetrahydrofuran is a key intermediate for the synthesis of the third-generation nicotinic insecticide dinotefuran (see Japanese patent document JPH07173157A), and is also a key intermediate for other new drugs (see international patent documents WO2015123365A1 and WO2015162456A1) .

[0003] At present, the synthetic method of 3-aminomethyltetrahydrofuran mainly contains following three kinds:

[0004] (1) Diethyl malonate and ethyl chloroacetate are used as starting materials to produce triethyl 1,2,2-ethanetricarboxylate through nucleophilic substitution reaction under the action of alkaline catalyst sodium ethoxide, Then it is reduced to 2-hydroxymethyl-1,4-butanediol by sodium borohydride, and then 3-hydroxymethyltetrahydrofuran is synthesized by self-...

Examples

Embodiment 1）

[0029] The preparation method of the 3-aminomethyltetrahydrofuran of the present embodiment has the following steps:

[0030] ①Add 106.0g of acrylonitrile and 161.0g of 2-chloroethanol into a four-neck flask, add 10.0g of sodium hydroxide in batches under stirring, and keep it at 25±5°C for 2 hours after the addition, and control it in the sampling center to Raw material disappears.

[0031] The solid was removed by filtration, and the filtrate was concentrated to dryness under reduced pressure at a temperature of 50±5°C to obtain 158.6 g of 2-chloroethyl-2-cyanoethyl ether as a colorless oily liquid with a yield of 59.4%.

[0032] ②Add 158.6g of 2-chloroethyl-2-cyanoethyl ether prepared in step ① and 800mL of tetrahydrofuran into a four-necked flask, cool to 0-5°C, add 47.2g of sodium amide in batches, and then heat up to reflux, Insulate the reaction for 6 hours, and control the sampling until the raw materials disappear.

[0033] Stop heating, cool to room temperature (15...

technical field

[0001] The invention belongs to the technical field of fine chemical synthesis, and in particular relates to a preparation method of 3-aminomethyltetrahydrofuran. Background technique

[0002] 3-Aminomethyltetrahydrofuran is a key intermediate for the synthesis of the third-generation nicotinic insecticide dinotefuran (see Japanese patent document JPH07173157A), and is also a key intermediate for other new drugs (see international patent documents WO2015123365A1 and WO2015162456A1) .

[0003] At present, the synthetic method of 3-aminomethyltetrahydrofuran mainly contains following three kinds:

[0004] (1) Diethyl malonate and ethyl chloroacetate are used as starting materials to produce triethyl 1,2,2-ethanetricarboxylate through nucleophilic substitution reaction under the action of alkaline catalyst sodium ethoxide, Then it is reduced to 2-hydroxymethyl-1,4-butanediol by sodium borohydride, and then 3-hydroxymethyltetrahydrofuran is synthesized by self-...

Examples

Embodiment 1）

[0029] The preparation method of the 3-aminomethyltetrahydrofuran of the present embodiment has the following steps:

[0030] ①Add 106.0g of acrylonitrile and 161.0g of 2-chloroethanol into a four-neck flask, add 10.0g of sodium hydroxide in batches under stirring, and keep it at 25±5°C for 2 hours after the addition, and control it in the sampling center to Raw material disappears.

[0031] The solid was removed by filtration, and the filtrate was concentrated to dryness under reduced pressure at a temperature of 50±5°C to obtain 158.6 g of 2-chloroethyl-2-cyanoethyl ether as a colorless oily liquid with a yield of 59.4%.

[0032] ②Add 158.6g of 2-chloroethyl-2-cyanoethyl ether prepared in step ① and 800mL of tetrahydrofuran into a four-necked flask, cool to 0-5°C, add 47.2g of sodium amide in batches, and then heat up to reflux, Insulate the reaction for 6 hours, and control the sampling until the raw materials disappear.

[0033] Stop heating, cool to room temperature (15...