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6,7-dihydroligustilide and alkylidene phthalide synthesis method

A technology of ligustilide and dihydrogen, which is applied in the field of synthesis of some compounds, can solve the problems of high cost, difficult to control the reaction, and energy consumption, and achieve the effect of low synthesis cost, easy operation, and easy reaction

Inactive Publication Date: 2008-11-05
LANZHOU UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, dialkylated products are unavoidable in this reaction
In order to obtain monoalkylated products, the prior art mostly converts carboxylic acid derivatives into acid chlorides or turns them into lithium salts, and then reacts them with other metal alkyl compounds or with alkyllithium. The reaction process complex and expensive
Especially when synthesizing the precursor raw material of 6,7-dihydroligustilide, refer to S.B.Li et al, Syn.Commun., 23,2051, (1993), be to use Brich reduction reaction, specifically use phthalic di Formic anhydride is carried out in liquid ammonia at low temperature. In addition, metal sodium is used as a reducing agent, which is dangerous and difficult to operate. Especially in large-scale synthesis, the reaction is difficult to control, the yield is not high and the operation is complicated.
However, in the alkylation reaction with butyllithium, butyllithium with high cost is used, and the reaction is performed at an extremely low temperature, which requires a large cooling capacity, consumes energy, has complex equipment, and often has environmental impacts. A certain degree of influence; in addition, the by-products of dialkylation are unavoidable, which increases the difficulty of separation

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0018] Example 1: Synthesis of 6,7-dihydroligustilide

[0019] a: Synthesis of 1-cyclohexene-1,2-dianhydride

[0020] The present invention is that 0.066 mole is 10 grams of 4-cyclohexene-1, the mixed solid of 2-dioic anhydride and 0.5 grams of palladium carbon (3%) is heated to 130 ℃ and stirred for twelve hours, and the product is dissolved with chloroform , Palladium carbon was removed by filtration, and the solvent was distilled off to obtain 9.9 g of white wax flake crystals.

[0021] b: Alkylation reaction

[0022] Dissolve 0.05 mole, that is, 7.60 grams of 1-cyclohexene-1,2-dioic anhydride and 0.1 gram of cuprous iodide in anhydrous tetrahydrofuran, under argon protection, at room temperature, add dropwise 0.1 mole (with 2.4 grams of metal Magnesium and 13.7g of brominated n-butane in 60ml of anhydrous ether) alkyl Grignard reagent, add Grignard reagent dropwise for about half an hour, react for 5-6 hours, add dilute hydrochloric acid 2mol / L Quench the reaction with ...

example 2

[0023] Example 2: Synthesis of Butenylphthalide

[0024] 0.05 moles, that is, 7.4 grams of phthalic anhydride and 0.1 grams (less than 2%) CuI of a catalytic amount were dissolved in 50 ml of anhydrous tetrahydrofuran, under argon protection, 0.1 moles were added dropwise under stirring at room temperature (with 2.4 grams of metal magnesium and 13.7g of n-bromobutane in 60ml of anhydrous ether) alkyl Grignard reagent, add Grignard reagent dropwise for about half an hour, react for 12-15 hours, add dilute hydrochloric acid 2mol / L solution 20ml Quench the reaction, extract with 25ml×3 ether, wash the ether extract with 25ml of saturated sodium bicarbonate solution for 3-5 times, wash with saturated saline solution for 1-2 times, dry over anhydrous magnesium sulfate, and evaporate the solvent to obtain a crude product. Dissolve the product in benzene, add a little p-toluenesulfonic acid to reflux for dehydration for two hours, and after cooling, quickly wash with saturated soluti...

example 3

[0025] Example 3: Synthesis of Acrylphthalide

[0026] 0.05 moles, that is, 7.4 grams of phthalic anhydride and 0.1 grams (less than 2%) CuI of a catalytic amount were dissolved in 50 ml of anhydrous tetrahydrofuran, under argon protection, 0.1 moles were added dropwise under stirring at room temperature (with 2.4 grams of metal magnesium and 12.3g of n-propane bromide in 60ml of anhydrous ether) alkyl Grignard reagent, add Grignard reagent dropwise for about half an hour, react for 12-14 hours, add dilute hydrochloric acid 2mol / L solution 20ml to quench Quench the reaction, extract with 25ml×3 ether, wash the ether extract with 25ml of saturated sodium bicarbonate solution for 3-5 times, wash with saturated saline solution for 1-2 times, dry over anhydrous magnesium sulfate, and evaporate the solvent to obtain the crude product. Soluble in benzene, add a little p-toluenesulfonic acid to reflux for dehydration for two hours, after cooling, quickly wash with saturated solution ...

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PUM

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Abstract

The invention discloses a new synthetic method of several perfumes and medical intermediate compound, which comprises the following steps: heating 4-cyclohexene-1, 2-bianhydrides to produce 1-cyclohexene-1, 2-bianhydrides under the palladium catalyst; making Grignard reagent of alkyl and 1-cyclohexene-1, 2-bianhydrides or ortho-phthalic anhydride react to produce 6, 7-dihydro-ligustilide and phthalic monoalkyl benzene. The invention is simple to convenient, which improves the obtaining rate.

Description

Technical field: [0001] The present invention relates to a new method for synthesizing some spices and pharmaceutical intermediates, specifically, a method for synthesizing some compounds of phthalides. Background technique: [0002] (3Z)-3-n-butene-4,5,6,7-tetrahydroisobenzofuran-1-3(hydrogen)-one (6,7-dihydroligustilide), (3z)- Both n-butenylphthalide and 3-n-butylphthalide (apigenin A) have a good smell. Adding an appropriate amount of phthalides to soaps and fruit juices will produce a pleasant fragrance. They have long since become commonly used spices. In addition, this type of compound also has good pharmacological activity. For example, n-butenylphthalide has anticholinergic effect, is an antispasmodic component of Angelica sinensis, has a strong inhibitory effect on uterine contraction, and can also affect animal trachea. Smooth muscle has a significant relaxation effect, so it also has an antiasthmatic effect. The n-butylphthalide obtained by further hydrogenati...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D307/89C07D307/88
Inventor 李绍白吴莉叶谦
Owner LANZHOU UNIVERSITY
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