IES87005B2 - Flavones glycoside drug intermediates acetylene carboxylic acid synthesis method - Google Patents

Abstract

The present invention discloses flavones glycoside drug intermediates acetylene carboxylic acid synthesis method, comprises the following steps: 3-propargyl, sodium nitrate solution were added to the reaction vessel, controlled the stirring speed, controlled the temperature of the solution, reacted, added ethyl tert butyl ether solution, raised the temperature of the solution, reacted., added antimony pentachloride powder, and dihydrin diacetate solution, raised the temperature of the solution, continued to react, extracted several times with ethyl tert butyl ether solution, set aside, solution stratification, separated reservoir, washed with the potassium chloride solution for several times, washed with the 3-methyl-2-amyl ketone solution for several times, washed with the dipropylene glycol solution for several times, re-crystallized in the 1, 3-dimethylcyclohexane solution, dehydrated with dehydration, got the finished product acetylene carboxylic acid. <Figure 1>

Description

The present invention relates to a method for preparing a pharmaceutical intermediate which belongs to the field of organic synthesis, more particularly, relates to flavones glycoside drug intermediates acetylene carboxylic acid synthesis method.

GENERAL BACKGROUND Acetylene carboxylic acid is mainly used for the synthesis of flavones glycosides drug, flavones glycoside is a kind of tea poly-phenol belonging to the flavones. Flavones are found in nature, and have the structure of 2-phenyl primary ketone. There is a keto-carbonyl in their molecules, the oxygen atom on the first is alkaline, it can become salt with acid, it’s hydroxyl derivatives are yellow, so it is also called yellow pigment or flavones. In general, it has the function of lowering blood pressure, anti-bacterial and regulating blood camp osmotic pressure, and it has also been found to inhibit tumor cells and protect against ultraviolet damage. However, most of the existing synthesis methods are using the process that stirring the mixture of propiolic alcohol with acetone, and added sulfuric acid solution at 20°C, when finished addition stirred at room temperature for 14h, made propiolic acid. This method of production requires using the chromic acid sulfuric acid solution, the chromic acid pollutes environment, the cost of follow-up pollution treatment is higher, the sulfuric acid solution acts as a reactant which increases the risk coefficient of the reaction process, and the synthesis method is complicated and the final yield is not very high. Therefore, it is necessary to propose a new synthesis method.

SUMMARY Based on the technical problems of the background technology, the purpose of the present invention is to provide flavones glycosides drug intermediates acetylene carboxylic acid synthesis method, comprises the following steps: A: 3-propargyl, 1.5 L sodium nitrate solution were added to the reaction vessel, controlled the stirring speed at 210-230 rpm, controlled the temperature of the solution to 25-30 °C, reacted for 60-80 min, added 800ml ethyl tert butyl ether solution, raised the temperature of the solution to 40-45 °C, reacted for 1 -2 h; B: added antimony pentachloride powder, and dihydrin diacetate solution, raised the temperature of the solution to 50-56 °C, continued to react for 30-50 min, extracted several times with ethyl tert butyl ether solution, set aside 2-3h, solution stratification, separated reservoir, washed with the potassium chloride solution for several times, washed with the 3-methyl-2-amyl ketone solution for several times, washed with the dipropylene glycol solution for several times, re-crystallized in the 1, 3-dimethylcyclohexane solution, dehydrated with dehydration, got the finished product acetylene carboxylic acid.

Preferably, the sodium nitrate solution has a mass fraction of 10-16%.

Preferably, the mass fraction of the ethyl tert butyl ether solution is 20-27%.

Preferably, the dihydrin diacetate solution has a mass fraction of 40-46%.

Preferably, the potassium chloride solution has a mass fraction of 15-22%.

Preferably, the mass fraction of 3-methyl-2-amyl ketone solution is 50-55%.

Preferably, the dipropylene glycol solution has a mass fraction of 60-67%. Preferably, the mass fraction of 1, 3-dimethylcyclohexane solution is 80-85%. Throughout the reaction process can be the following reaction formula: CH CHIII IIIc θ C8HI4O5 + Cl5Sb -------►I o^CxOh h2n Compared with the synthetic method disclosed in the background art, the invention provides flavones glycoside drug intermediates acetylene carboxylic acid synthesis method, it is unnecessary to use chromic acid sulfuric acid solution as reaction and raw materials, avoiding the environmental pollution of chromic anhydride and reducing the cost of follow-up pollution treatment, meanwhile avoiding the influence of high-risk chemicals such as sulfuric acid on the safety factor, reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same time, the present invention provides a new synthetic route which has offered a good foundation for further enhancing the yield of the reaction.

DESCRIPTION OF THE DRAWINGS Figure 1 is the infrared analysis spectrum of finished product acetylene carboxylic acid.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS The following examples with reference to specific embodiments of the present invention are further illustrated: Embodiment 1 Flavones glycoside drug intermediates acetylene carboxylic acid synthesis method, comprises the following steps: A: 2mol 3-propargyl, 1.5 L sodium nitrate solution with a mass fraction of 10% were added to the reaction vessel, controlled the stirring speed at 210 rpm, controlled the temperature of the solution to 25 °C, reacted for 60 min, added 800ml ethyl tert butyl ether solution with a mass fraction of 20%, raised the temperature of the solution to 40 °C, reacted for 1 h; B: added 2 mol antimony pentachloride powder, and 4 mol dihydrin diacetate solution with a mass fraction of 40%, raised the temperature of the solution to 50°C, continued to react for 30 min, extracted three times with ethyl tert butyl ether solution, set aside 2h, solution stratification, separated reservoir, washed with the potassium chloride solution with a mass fraction of 15% for five times, washed with the 3-methyl-2-amyl ketone solution with a mass fraction of 50% for six times, washed with the dipropylene glycol solution with a mass fraction of 60% for eight times, re-crystallized in the 1,3-dimethylcyclohexane solution with a mass fraction of 80%, dehydrated with activated alumina dehydration, got the finished product acetylene carboxylic acid 120.4g, yield of 86%.

Embodiment 2 Flavones glycoside drug intermediates acetylene carboxylic acid synthesis method, comprises the following steps: A. 2mol 3-propargyl, 1.5 L sodium nitrate solution with a mass fraction of 13% were added to the reaction vessel, controlled the stirring speed at 220 rpm, controlled the temperature of the solution to 27 °C, reacted for 70 min, added 800ml ethyl tert butyl ether solution with a mass fraction of 25%, raised the temperature of the solution to 43 °C, reacted for 1.5 h; B: added 2.5 mol antimony pentachloride powder, and 4.5 mol dihydrin diacetate solution with a mass fraction of 43%, raised the temperature of the solution to 52°C, continued to react for 40 min, extracted four times with ethyl tert butyl ether solution, set aside 2.5h, solution stratification, separated reservoir, washed with the potassium chloride solution with a mass fraction of 18% for six times, washed with the 3-methyl-2-amyl ketone solution with a mass fraction of 54% for seven times, washed with the dipropylene glycol solution with a mass fraction of 65% for nine times, re-crystallized in the 1,3-dimethylcyclohexane solution with a mass fraction of 83%, dehydrated with anhydrous magnesium sulfate dehydration, got the finished product acetylene carboxylic acid 127.4g, yield of 91%.

Embodiment 3 Flavones glycoside drug intermediates acetylene carboxylic acid synthesis method, comprises the following steps: A: 2mol 3-propargyl, 1.5 L sodium nitrate solution with a mass fraction of 16% were added to the reaction vessel, controlled the stirring speed at 230 rpm, controlled the temperature of the solution to 30 °C, reacted for 80 min, added 800ml ethyl tert butyl ether solution with a mass fraction of 27%, raised the temperature of the solution to 45 °C, reacted for 2 h; B: added 3 mol antimony pentachloride powder, and 5 mol dihydrin diacetate solution with a mass fraction of 46%, raised the temperature of the solution to 56°C, continued to react for 50 min, extracted five times with ethyl tert butyl ether solution, set aside 3h, solution stratification, separated reservoir, washed with the potassium chloride solution with a mass fraction of 22% for seven times, washed with the 3-methyl-2-amyl ketone solution with a mass fraction of 55% for eight times, washed with the dipropylene glycol solution with a mass fraction of 67% for ten times, 5 re-crystallized in the 1,3-dimethylcyclohexane solution with a mass fraction of 85%, dehydrated with phosphorus pentoxide dehydration, got the finished product acetylene carboxylic acid 131,6g, yield of 94%.

Infrared analysis of finished product acetylene carboxylic acid, infrared spectrum is shown in figure 1, the analysis of data is shown in Table 1: Table 1 Peak data Serial Peak position Transmittance Half width Peak difference number (cm'1) (%) (cm'1) (%) 1 521 45 17 31 2 601 62 47 14 3 651 54 37 18 4 695 61 64 10 5 756 63 110 10 6 857 67 22 8 7 1267 10 35 75 8 1405 43 22 48 9 1704 9 44 84 10 2119 50 31 47 11 3065 62 460 19 12 3303 43 26 41 The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive 15 concept be replaced or modified equivalently with reference to the range of the invention.

Claims (4)

Claims

1. Flavones glycoside drug intermediates acetylene carboxylic acid synthesis method, comprise the following steps: A: 3-propargyl, 1.5 L sodium nitrate solution were added to the reaction vessel, controlled the stirring speed at 210-230 rpm, controlled the temperature of the solution to 25-30 °C, reacted for 60-80 min, added 800ml ethyl tert butyl ether solution, raised the temperature of the solution to 40-45 °C, reacted for 1-2 h; B: added antimony pentachloride powder, and dihydrin diacetate solution, raised the temperature of the solution to 50-56 °C, continued to react for 30-50 min, extracted several times with ethyl tert butyl ether solution, set aside 2-3h, solution stratification, separated reservoir, washed with the potassium chloride solution for several times, washed with the 3-methyl-2-amyl ketone solution for several times, washed with the dipropylene glycol solution for several times, re-crystallized in the 1, 3-dimethylcyclohexane solution, dehydrated with dehydration, got the finished product acetylene carboxylic acid.

2. Flavones glycoside drug intermediates acetylene carboxylic acid synthesis method according to claim 1 wherein the sodium nitrate solution has a mass fraction of 10-16%.

3. Flavones glycoside drug intermediates acetylene carboxylic acid synthesis method according to claim 1 wherein the mass fraction of the ethyl tert butyl ether solution is 20-27%.

4. Flavones glycoside drug intermediates acetylene carboxylic acid synthesis method according to claim 1 wherein the dihydrin diacetate solution has a mass fraction of 40-46%.