3,5-dihydroxyamylbenzene synthesis method

Abstract

The present invention provides a 3,5-dihydroxyamylbenzene synthesis method, which comprises: carrying out a Friedel-crafts acylation reaction on benzene under the catalysis of an acid to obtain valerophenone, wherein the acid is a Lewis acid; carrying out a nitrification reaction on the obtained valerophenone to obtain 3,5-dinitrovalerophenone; reducing the carbonyl into methylene, and reducing the nitro group to obtain 3,5-diaminoamylbenzene; and diazotizing the 3,5-diaminoamylbenzene to change into the hydroxy group so as to obtain the 3,5-dihydroxyamylbenzene. According to the present invention, the used raw materials are bulk chemical industry raw materials with low price and easy availability, the conditions of each reaction are relatively mild, the reactions belong to a large numberof the conventional reactions used in the chemical industry, and the final product 3,5-dihydroxyamylbenzene (Olivetol) obtained according to the process has high purity, wherein the purity can achievemore than 98.5%, and the single impurity is within 0.3%.

Description

technical field [0001] The invention relates to a new synthesis process of an important pharmaceutical intermediate 3,5-dihydroxypentylbenzene (CAS: 500-66-3), which belongs to the technical field of organic synthesis. Background technique [0002] 3, 5-dihydroxypentylbenzene (Olivetol) was first obtained by degrading lichenic acid (also known as D-usnic acid, pentyl ithenalic acid) extracted from lichen plants, and 3, 5- The yield of dihydroxypentylbenzene is very low. Since the discovery of 3,5-dihydroxypentylbenzene, there have been many reports on its synthesis. According to the raw materials, it can be divided into two categories. One is synthesized from raw materials without benzene rings, and the other is synthesized from raw materials containing benzene rings. synthesis. [0003] First, starting from raw materials that do not contain benzene rings: [0004] Mamor et al. used n-hexanal as a raw material to generate 2-octenoic acid ethyl ester through Witting reacti...

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Problems solved by technology

[0002] 3, 5-dihydroxypentylbenzene (Olivetol) was first obtained by degrading lichenic acid (also known as D-usnic acid, pentyl ithenalic acid) extracted from lichen plants, and 3, 5- The yield of dihydroxypentylbenzene is very low

[0021] The disadvantage is that 3-oxoglutaric acid diester is not commercially available, and the synthesis is relatively troublesome. The witting reagent used in the synthesis of ethyl 2-octenoate is expensive, making it difficult to reduce the synthesis route.

[0024] The dimethyl ketal of 3-oxooctanoic acid methyl ester and 1,3-dimethylsiloxy-1-methoxybutadiene are complicated to synthesize and are not suitable as the starting point for the synthesis of 3,5-dihydroxypentylbenzene raw material

[0027] The disadvantage of this route is that 5-methyl-1,3-cyclohexanedione is difficult to obtain in large quantities, and the prices of iodine, di-n-butyl copper lithium and trimethyl iodosilane are relatively high

The unit price of 3,5-dihydroxybenzoic acid is relatively expensive, so the cost of raw materials for the above-mentioned routes must not be low

For example, lithium aluminum tetrahydride, butyl lithium (or pentyl lithium), n-butylmagnesium bromide (or n-magnesium bromide) are sensitive to moisture and air, dimethyl sulfate is a highly toxic compound, phosphorus pentachloride , Phosphorus tribromide, etc. are highly toxic and corrosive to equipment. Palladium-carbon hydrogenation itself has great safety hazards and requires pressurization. Demethylation requires high temperature, etc.

[0034] In general, the current synthetic routes starting from raw materials containing benzene rings have obvious deficiencies, and are not particularly suitable for the industrial production of 3, 5-dihydroxypentylbenzene (Olivetol)

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