CN112125876A - Synthetic method of 3-isochromone - Google Patents
Synthetic method of 3-isochromone Download PDFInfo
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- CN112125876A CN112125876A CN202010862832.XA CN202010862832A CN112125876A CN 112125876 A CN112125876 A CN 112125876A CN 202010862832 A CN202010862832 A CN 202010862832A CN 112125876 A CN112125876 A CN 112125876A
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Abstract
The invention belongs to the technical field of synthesis of organic intermediates, and particularly relates to a synthesis method of 3-isochromone, which comprises the following steps: (1) synthesizing o-methyl benzyl chloride by taking o-xylene as a raw material; (2) synthesizing o-methyl phenylacetonitrile by taking o-methyl benzyl chloride as a raw material; (3) synthesizing sodium o-tolylacetate by taking o-tolylacetonitrile as a raw material; (4) synthesizing o-tolylacetic acid by using o-tolylsodium acetate as a raw material; (5) synthesizing 2-chloromethyl phenylacetic acid by taking o-methyl phenylacetic acid as a raw material; (6) 2-chloromethyl phenylacetic acid is used as a raw material to synthesize the 3-isochromone. The synthesis method of the 3-isochromone has the advantages of simple reaction process, readily available raw materials, mild reaction conditions, high product yield and the like, and has the advantages of low production cost, high yield, high product purity, good quality, low production waste discharge and the like, the product purity is more than or equal to 99.5 percent, the production yield is more than or equal to 92 percent, and the product meets the use requirements of foreign high-end users.
Description
Technical Field
The invention belongs to the technical field of synthesis of organic intermediates, and particularly relates to a synthesis method of 3-isochromone.
Background
Compared with triazole bactericides, the methoxyl acrylate bactericides have the future. In 2016, this class of product, with a total sales of $ 33.96 million and a dominance gap of $ 4.21 million, freezes the world-wide triazole fungicide at position 2 of the global fungicide market. Among the first fifteen worldwide fungicides, the strobilurin fungicides account for 3 seats, and azoxystrobin, pyraclostrobin and picoxystrobin weigh one pound.
Azoxystrobin is not only the leading old in the global fungicide market, but also the first large product in the rice fungicide market. In 2016, the first three products of the rice bactericide market are sequentially as follows: azoxystrobin, tricyclazole and difenoconazole, which are sold on rice in sequence as follows: 1.18 billion, 1.10 billion, and 0.56 billion dollars. Under the rate of azoxystrobin, strobilurin fungicides are more or less used in the rice fungicide market.
Obviously, the commercial development of the methoxy acrylic ester bactericides has been successful greatly, and in 2016, the products occupy more than 1/5 of the global bactericide market, and are drawn out from various bactericides. In more than ten methoxy acrylate bactericides on the market at present, the total sale of the first six products in 2016 years accounts for more than 97.0 percent, and the total sale is absolutely dominating.
Like other products, strobilurin fungicides also become trapped in resistant vortices, and many of them suffer from intense competition from non-proprietary products due to patent expiration. Development of compound products, development and cooperation with other companies, and the like become a project and good strategy.
In 2016, the methoxy acrylate fungicide sales were in the $ 33.96 million, 22.2% of the $ 152.68 million global fungicide market (including non-crop fungicides), and 6.0% of the $ 564.52 million global total pesticide market (including non-crop pesticides). In the year, the sales volume of the products is reduced by 5.1 percent on a par; the compound year growth rate is 1.4% in 2011-2016, and the market shows the trend of first promotion and then inhibition; and created the highest history record of $ 37.43 billion in 2014. In 2016, the first six major products in the methoxy acrylate bactericides comprise: the sale amount of 2016 of 6 products is more than 1.00 hundred million dollars, the total sale amount is 33.00 hundred million dollars, and the market share of the products is as high as 97.2%. Particularly, the sales of the first three major varieties are more than 6.00 hundred million dollars, and the total sales amount reaches 78.7 percent of the total market of the products.
The market performance of the methoxy acrylic ester bactericide provides wide market space and good development prospect for series products such as 3-isochromanone which is an important raw material for producing the bactericide, an intermediate 3-methoxy-2- (2-chloromethyl) methyl phenylacrylate and the like. The strobilurin fungicide not only has a novel action mechanism, a very wide fungicide spectrum and good environmental compatibility, but also can keep the cereal crops green until before harvest, thereby improving the yield and quality of the crops, which is beyond the triazole fungicide, and is the main fungicide in the European grain market at present. According to the demand of 3-isochromanone from more than 300 tons in 2009 to more than 2000 tons in 2018, the methoxy acrylic ester bactericides are continuously expanded. From literature reports, the existing synthesis method has the following defects, such as harsh conditions, high cost, difficult operation, low conversion rate, long reaction time, low yield and the like. Which greatly restricts the industrial mass production thereof. Therefore, a more efficient and economic method for synthesizing 3-isochromanone is urgently needed to be found, so that the synthesis cost is reduced, the industrial production is realized, and meanwhile, the synthesis cost of related subsequent products and related drug molecules is greatly reduced, so that great economic benefits are brought.
Disclosure of Invention
The invention aims to provide a synthetic method of 3-isochromone.
The realization process of the invention is as follows:
a method for synthesizing 3-isochromone comprises the following steps:
(1) synthesizing o-methyl benzyl chloride by taking o-xylene as a raw material;
(2) synthesizing o-methyl phenylacetonitrile by taking o-methyl benzyl chloride as a raw material;
(3) synthesizing sodium o-tolylacetate by taking o-tolylacetonitrile as a raw material;
(4) synthesizing o-tolylacetic acid by using o-tolylsodium acetate as a raw material;
(5) synthesizing 2-chloromethyl phenylacetic acid by taking o-methyl phenylacetic acid as a raw material;
(6) 2-chloromethyl phenylacetic acid is used as a raw material to synthesize the 3-isochromone.
Further, the specific process of the step (1) is that in a closed container, o-xylene is firstly added, the temperature is raised to 95-100 ℃, then chlorine is introduced, and the reaction is carried out for 4-6 hours under the action of a light source to obtain o-methyl benzyl chloride; wherein the wavelength of the light source is selected to be 500-3000 nm.
Further, the molar ratio of o-xylene to chlorine gas is 2: 1-2: 1.2.
further, rectifying and purifying the o-methylbenzyl chloride obtained in the step (1) to obtain the o-methylbenzyl chloride with the purity of more than 99%.
Further, the specific process of the step (2) is that 25-30% of sodium cyanide aqueous solution by mass percent is added into a closed container, the temperature is raised to 30-100 ℃, o-methyl benzyl chloride with the purity of more than 99% is dripped, a quaternary ammonium salt catalyst, an alkali binding agent and boric acid are added, the temperature is controlled to be 30-100 ℃, heat preservation reaction is carried out, when the content of the o-methyl benzyl chloride is less than 0.1%, the heat preservation reaction is finished, water is fully added into the container, standing is carried out for 1-1.5 hours, layering is carried out, and the o-methyl benzyl cyanide is obtained through distillation.
Further, the molar ratio of sodium cyanide to ortho-methylbenzyl chloride was 1.2: 1-1.2: 1.1, the mass ratio of the o-methyl benzyl chloride to the quaternary ammonium salt catalyst is 1: 0.004-1: 0.006, o-methylbenzyl chloride: alkali binding agent: the molar ratio of boric acid is 100: 0.5: 1; the quaternary ammonium salt catalyst is selected from any one of benzyltriethylammonium chloride, tetramethylammonium chloride, tetrabutylammonium bromide or octyltrimethylammonium chloride; the alkali binding agent is selected from zinc chloride, ferric trichloride or anhydrous aluminum trichloride.
Further, adding 30% by mass of an aqueous solution of sodium hydroxide into a closed container, then adding o-tolylacetonitrile, heating to 95-103 ℃ for reflux, carrying out reflux heat preservation reaction for 6-8 h, and when the peak of the o-tolylacetonitrile is less than 0.1% after gas chromatography analysis, finishing the heat preservation reaction to reach the hydrolysis end point to obtain a hydrolysis product, namely, o-tolylsodium acetate; wherein, the ratio of sodium hydroxide: the molar ratio of the o-methyl phenylacetonitrile is 1.5: 1-1.5: 1.1.
Further, the specific process of the step (4) is to adjust the pH value of the water layer of the hydrolyzed product of the sodium o-tolylacetate to 2-3 by hydrochloric acid, separate out solids, cool the solids to below 20 ℃, centrifuge the solids to obtain wet products, and rinse the acidity of the hydrochloric acid by water during centrifugation to obtain the o-tolylacetic acid, wherein the hydrochloric acid is 30% by mass.
Further, adding o-tolylacetic acid and dichloroethane in a closed container, heating to 75-80 ℃, adding azobisisobutyronitrile, starting to introduce chlorine, stopping reaction until the content of the raw materials is 1% -5%, cooling and centrifuging to obtain 2-chloromethyl phenylacetic acid solid; wherein the mass ratio of the o-tolylacetic acid to the dichloroethane is 2: 1-2: 1.1, the mass ratio of o-tolylacetic acid to azobisisobutyronitrile is 10: 1-10: 1.1, the mass ratio of the o-tolylacetic acid to the chlorine is 1.8: 1-1.8: 1.1.
further, adding 2-chloromethyl phenylacetic acid solid and water into a closed container, heating to 50-60 ℃, slowly adding sodium bicarbonate solid for hydrolysis reaction, stopping the reaction when the content of the 2-chloromethyl phenylacetic acid is below 0.3%, and drying to obtain 3-isochromanone solid after suction filtration, cyclohexane washing and water washing; wherein the mass ratio of the 2-chloromethyl phenylacetic acid solid to the water is 1: 3-1: 3.2, the mass ratio of the 2, 2-chloromethyl phenylacetic acid solid to the sodium bicarbonate solid is 2: 1-2: 1.1.
the invention has the following positive effects:
(1) the synthesis method of the 3-isochromone has the advantages of simple reaction process, readily available raw materials, mild reaction conditions, high product yield and the like, and has the advantages of low production cost, high yield, high product purity, good quality, low production waste discharge and the like, the product purity is more than or equal to 99.5 percent, the production yield is more than or equal to 92 percent (the yield is improved by 30 percent compared with the yield reported by documents), and the product meets the use requirements of foreign high-end users.
(2) The application of new technologies such as alkalization technology and the like realizes the stability and controllability of the whole production process. The content of single impurity in the total product is less than 0.1 percent (w/w percent), thereby effectively ensuring the product quality. Compared with the process technology reported in the literature, the project technology has the characteristics of simple reaction process, easily obtained raw materials, mild reaction conditions, greatly reduced three-waste discharge amount, no generation and discharge of allergen in the production process, environmental-friendly production and the like.
(3) The method adopts classical reactions, the reaction mechanism is well understood, the o-xylene chlorination in the step (1) usually reacts to 20% of benzyl monochloride to generate a benzyl dichloride peak, and the selection of the light wavelength in the invention realizes that the benzyl dichloride peak is generated only after the benzyl monochloride reaches 45%, thereby increasing the selectivity of the benzyl monochloride. In the step (5), dichloride is generated when the 2-chloromethyl phenylacetic acid is subjected to acid chlorination to reach more than 95 percent, so that the yield is ensured.
(4) In the cyaniding process of the step (2), an alkali binding agent and boric acid are added on the basis of the conventional reaction, so that the influence on the yield due to self polymerization caused by high temperature in the cyaniding process of the o-tolylacetonitrile is prevented.
Detailed Description
The present invention will be further described with reference to the following examples.
The synthesis method of the 3-isochromone comprises the following steps:
(1) the o-methyl benzyl chloride is synthesized by taking o-xylene as a raw material, and the reaction equation is as follows:
(2) the o-methylbenzyl cyanide is synthesized by taking o-methylbenzyl chloride as a raw material, and the reaction equation is as follows:
(3) the method is characterized in that o-methyl phenylacetonitrile is used as a raw material to synthesize o-methyl sodium phenylacetate, and the reaction equation is as follows:
(4) the o-tolylacetic acid is synthesized by using o-tolylsodium acetate as a raw material, and the reaction equation is as follows:
(5) the method comprises the following steps of (1) synthesizing 2-chloromethyl phenylacetic acid by taking o-methyl phenylacetic acid as a raw material, wherein the reaction equation is as follows:
(6) synthesizing 3-isochromone by using 2-chloromethyl phenylacetic acid as a raw material, wherein the reaction equation is as follows:
example 1
The synthesis method of 3-isochromone described in this embodiment includes the following steps:
(1) synthesizing o-methyl benzyl chloride by taking o-xylene as a raw material;
the specific process of the step (1) is that 2332g (22mol) of o-xylene is firstly added into a 3000-liter reaction bottle, the temperature is raised to 100 ℃, then 781g (11mol) of chlorine gas is introduced, the reaction is carried out for 5 hours under the action of a light source, the wavelength of the light source is selected to be 2500nm, o-methyl benzyl chloride is obtained, then the obtained o-methyl benzyl chloride is rectified and purified, and the o-methyl benzyl chloride with the purity of more than 99 percent is obtained.
(2) Synthesizing o-methyl phenylacetonitrile by taking o-methyl benzyl chloride as a raw material;
adding 1960g of sodium cyanide aqueous solution with the mass percent of 30% (wherein the mass percent of the sodium cyanide is 12mol) into a 3000-liter reaction bottle, heating to 100 ℃, dropwise adding 1400g (10mol) of o-methyl benzyl chloride, adding 5.6g of quaternary ammonium salt catalyst (benzyl triethyl ammonium chloride), 6.8g (0.05mol) of alkali binding agent (zinc chloride) and 6.1g (0.1mol) of boric acid, controlling the temperature to be maintained at 100 ℃, carrying out heat preservation reaction, finishing the heat preservation reaction when the content of the o-methyl benzyl chloride is less than 0.1%, filling water into a container, standing for 1.5h, layering, and distilling to obtain the o-methyl benzyl cyanide.
(3) Synthesizing sodium o-tolylacetate by taking o-tolylacetonitrile as a raw material;
adding 2000g (15mol) of sodium hydroxide aqueous solution with the mass percentage of 30% into a 3000L reaction bottle, then adding 1310g (10mol) of o-tolylacetonitrile, heating to 103 ℃, refluxing, carrying out heat preservation reaction for 8h, finishing the heat preservation reaction when the peak of the o-tolylacetonitrile is less than 0.1% after gas chromatography analysis, and reaching the hydrolysis end point to obtain the hydrolysis product of the o-tolylsodium acetate.
(4) Synthesizing o-tolylacetic acid by using o-tolylsodium acetate as a raw material;
and (4) regulating the pH value of the water layer of the hydrolyzed product of the sodium o-tolylacetate to 2-3 by using hydrochloric acid, separating out solids, cooling to below 20 ℃, centrifuging to obtain a wet product, and washing the acidity of the hydrochloric acid by using water during centrifugation to obtain the o-tolylacetic acid, wherein the hydrochloric acid is 30% in mass percentage.
(5) Synthesizing 2-chloromethyl phenylacetic acid by taking o-methyl phenylacetic acid as a raw material;
the specific process of the step (5) is that 800g of o-tolylacetic acid and 400g of dichloroethane are added into a 2000-liter reaction bottle, the temperature is raised to 80 ℃, then 80g of azobisisobutyronitrile is added, 444.44g of chlorine gas is introduced, the reaction is stopped when the content of the raw materials is 1-5%, the temperature is reduced, and the 2-chloromethyl phenylacetic acid solid is 850g obtained by centrifugation.
(6) 2-chloromethyl phenylacetic acid is used as a raw material to synthesize the 3-isochromone.
The specific process of the step (6) is that 850g of 2-chloromethyl phenylacetic acid solid and 2550g of water are added into a 3000-liter reaction bottle, the temperature is raised to 60 ℃, 425g of sodium bicarbonate solid are slowly added for hydrolysis reaction, when the content of the 2-chloromethyl phenylacetic acid is below 0.3 percent, the reaction is stopped, the impurity removing peak is removed by suction filtration and cyclohexane washing, after water washing for 15 minutes, the 3-isochromone solid is obtained by drying, and the yield is 81.2 percent.
Example 2
The synthesis method of 3-isochromone described in this embodiment includes the following steps:
(1) synthesizing o-methyl benzyl chloride by taking o-xylene as a raw material;
the specific process of the step (1) is that 2332g (22mol) of o-xylene is firstly added into a 3000-liter reaction bottle, the temperature is raised to 95 ℃, 937.2g (13.2mol) of chlorine is introduced, the reaction is carried out for 4 hours under the action of a light source, the wavelength of the light source is selected to be 3000nm, o-methyl benzyl chloride is obtained, and then the obtained o-methyl benzyl chloride is rectified and purified, so that the o-methyl benzyl chloride with the purity of more than 99 percent is obtained.
(2) Synthesizing o-methyl phenylacetonitrile by taking o-methyl benzyl chloride as a raw material;
the specific process of the step (2) is that 2352g of aqueous solution of 25 mass percent sodium cyanide (wherein the mass percent of sodium cyanide is 12mol) is added into a 3000-liter reaction bottle, the temperature is raised to 30 ℃, 1540g (11mol) of o-methylbenzyl chloride is dropwise added, 9.24g of quaternary ammonium salt catalyst (tetramethylammonium chloride), 8.91g (0.055mol) of alkali binding agent (ferric trichloride) and 6.71g (0.11mol) of boric acid are added, the temperature is controlled to be maintained at 30 ℃, a heat preservation reaction is carried out, when the content of the o-methylbenzyl chloride is less than 0.1 percent, the heat preservation reaction is finished, water is fully added into the container, the container is kept stand for 1h, layering is carried out, and the o-methylbenzonitrile is obtained through distillation.
(3) Synthesizing sodium o-tolylacetate by taking o-tolylacetonitrile as a raw material;
adding 2000g (15mol) of sodium hydroxide aqueous solution with the mass percentage of 30% into a 3000L reaction bottle, then adding 1441g (11mol) of o-tolylacetonitrile, heating to 95 ℃ for reflux, carrying out reflux heat preservation reaction for 6h, and when the peak of the o-tolylacetonitrile is less than 0.1% after gas chromatographic analysis, finishing the heat preservation reaction and reaching the hydrolysis end point to obtain the hydrolysis product of the o-tolylsodium acetate.
(4) Synthesizing o-tolylacetic acid by using o-tolylsodium acetate as a raw material;
and (4) regulating the pH value of the water layer of the hydrolyzed product of the sodium o-tolylacetate to 2-3 by using hydrochloric acid, separating out solids, cooling to below 20 ℃, centrifuging to obtain a wet product, and washing the acidity of the hydrochloric acid by using water during centrifugation to obtain the o-tolylacetic acid, wherein the hydrochloric acid is 30% in mass percentage.
(5) Synthesizing 2-chloromethyl phenylacetic acid by taking o-methyl phenylacetic acid as a raw material;
the specific process of the step (5) is that 800g of o-tolylacetic acid and 440g of dichloroethane are added into a 2000-liter reaction bottle, the temperature is raised to 75 ℃, 88g of azobisisobutyronitrile is added, 488.89g of chlorine gas is introduced, the reaction is stopped when the content of the raw materials is 1-5%, the temperature is reduced, and 870g of 2-chloromethyl phenylacetic acid solid is obtained by centrifugation.
(6) 2-chloromethyl phenylacetic acid is used as a raw material to synthesize the 3-isochromone.
The specific process of the step (6) is that 870g of 2-chloromethyl phenylacetic acid solid and 2784g of water are added into a 3000-liter reaction bottle, the temperature is raised to 50 ℃, 478.5g of sodium bicarbonate solid is slowly added for hydrolysis reaction, when the content of the 2-chloromethyl phenylacetic acid is below 0.3 percent, the reaction is stopped, the impurity removal peak is removed by suction filtration and cyclohexane washing, and after washing for 30 minutes, the 3-isochromone solid is obtained by drying, and the yield is 84.1 percent.
Example 3
The synthesis method of 3-isochromone described in this embodiment includes the following steps:
(1) synthesizing o-methyl benzyl chloride by taking o-xylene as a raw material;
the specific process of the step (1) is that 2332g (22mol) of o-xylene is firstly added into a 3000-liter reaction bottle, the temperature is raised to 100 ℃, then 781g (11mol) of chlorine gas is introduced, the reaction is carried out for 6 hours under the action of a light source, the wavelength of the light source is selected to be 500nm, o-methyl benzyl chloride is obtained, then the obtained o-methyl benzyl chloride is rectified and purified, and the o-methyl benzyl chloride with the purity of more than 99 percent is obtained.
(2) Synthesizing o-methyl phenylacetonitrile by taking o-methyl benzyl chloride as a raw material;
adding 1960g of sodium cyanide aqueous solution with the mass percent of 30% (wherein the mass percent of the sodium cyanide is 12mol) into a 3000-liter reaction bottle, heating to 100 ℃, dropwise adding 1400g (10mol) of o-methylbenzyl chloride, adding 7g (0.05mol) of quaternary ammonium salt catalyst (benzyltriethylammonium chloride), 6.8g (0.05mol) of alkali-binding agent (zinc chloride) and 6.1g (0.1mol) of boric acid, controlling the temperature to be maintained at 100 ℃, carrying out heat preservation reaction, finishing the heat preservation reaction when the content of the o-methylbenzyl chloride is less than 0.1%, filling water into a container, standing for 1.5h, layering, and distilling to obtain the o-methylbenzonitrile.
(3) Synthesizing sodium o-tolylacetate by taking o-tolylacetonitrile as a raw material;
adding 2000g (15mol) of sodium hydroxide aqueous solution with the mass percentage of 30% into a 3000L reaction bottle, then adding 1310g (10mol) of o-tolylacetonitrile, heating to 103 ℃, refluxing, carrying out heat preservation reaction for 7h, finishing the heat preservation reaction when the peak of the o-tolylacetonitrile is less than 0.1% after gas chromatography analysis, and reaching the hydrolysis end point to obtain the hydrolysis product of the o-tolylsodium acetate.
(4) Synthesizing o-tolylacetic acid by using o-tolylsodium acetate as a raw material;
and (4) regulating the pH value of the water layer of the hydrolyzed product of the sodium o-tolylacetate to 2-3 by using hydrochloric acid, separating out solids, cooling to below 20 ℃, centrifuging to obtain a wet product, and washing the acidity of the hydrochloric acid by using water during centrifugation to obtain the o-tolylacetic acid, wherein the hydrochloric acid is 30% in mass percentage.
(5) Synthesizing 2-chloromethyl phenylacetic acid by taking o-methyl phenylacetic acid as a raw material;
the specific process of the step (5) is that 800g of o-tolylacetic acid and 400g of dichloroethane are added into a 2000-liter reaction bottle, the temperature is raised to 80 ℃, then 80g of azobisisobutyronitrile is added, 444.44g of chlorine gas is introduced, the reaction is stopped when the content of the raw materials is 1-5%, the temperature is reduced, and the 2-chloromethyl phenylacetic acid solid is 850g obtained by centrifugation.
(6) 2-chloromethyl phenylacetic acid is used as a raw material to synthesize the 3-isochromone.
The specific process of the step (6) is that 850g of 2-chloromethyl phenylacetic acid solid and 2550g of water are added into a 3000-liter reaction bottle, the temperature is raised to 60 ℃, 425g of sodium bicarbonate solid are slowly added for hydrolysis reaction, when the content of the 2-chloromethyl phenylacetic acid is below 0.3 percent, the reaction is stopped, the impurity removal peak is removed by suction filtration and cyclohexane washing, after washing for 15 minutes, the 3-isochromone solid is obtained by drying, and the yield is 79.9 percent.
In the invention, the o-methylbenzyl chloride obtained in the step (1) is rectified and purified to obtain the o-methylbenzyl chloride with the purity of more than 99%, wherein the rectification and purification related to the o-methylbenzyl chloride can be realized by adopting the prior art, and the rectification and purification method for the o-methylbenzyl chloride comprises the following steps: and (3) adopting a continuous rectification method, keeping the temperature of the kettle at 150 ℃, keeping the top temperature at 110 ℃, separating heavy components and light components, keeping the content of o-xylene in the light components at 99%, mechanically chlorinating, continuously rectifying the heavy components again, and separating the finished product of o-methyl benzyl chloride. And evaporating the mixture of monochlorobenzyl and dichlorobenzyl of the ortho-xylene again to obtain a light component monochlorobenzyl and a heavy component dichlorobenzyl, and separating out a finished product of ortho-methylbenzyl chloride.
The foregoing is a more detailed description of the invention in connection with specific preferred embodiments and is not intended to limit the invention to the particular forms disclosed. For those skilled in the art to which the invention pertains, several simple deductions or substitutions can be made without departing from the spirit of the invention, and all shall be considered as belonging to the protection scope of the invention.
Claims (10)
1. A synthetic method of 3-isochromone is characterized by comprising the following steps:
(1) synthesizing o-methyl benzyl chloride by taking o-xylene as a raw material;
(2) synthesizing o-methyl phenylacetonitrile by taking o-methyl benzyl chloride as a raw material;
(3) synthesizing sodium o-tolylacetate by taking o-tolylacetonitrile as a raw material;
(4) synthesizing o-tolylacetic acid by using o-tolylsodium acetate as a raw material;
(5) synthesizing 2-chloromethyl phenylacetic acid by taking o-methyl phenylacetic acid as a raw material;
(6) 2-chloromethyl phenylacetic acid is used as a raw material to synthesize the 3-isochromone.
2. The method of synthesizing 3-isochromone according to claim 1, wherein: adding o-xylene into a closed container, heating to 95-100 ℃, introducing chlorine, and reacting for 4-6 hours under the action of a light source to obtain o-methyl benzyl chloride; wherein the wavelength of the light source is selected to be 500-3000 nm.
3. The method of synthesizing 3-isochromone according to claim 2, wherein: the molar ratio of o-xylene to chlorine is 2: 1-2: 1.2.
4. the method of synthesizing 3-isochromone according to claim 1 or 2, wherein: rectifying and purifying the o-methyl benzyl chloride obtained in the step (1) to obtain the o-methyl benzyl chloride with the purity of more than 99%.
5. The method of synthesizing 3-isochromone according to claim 4, wherein: adding 25-30% by mass of sodium cyanide aqueous solution into a closed container, heating to 30-100 ℃, dropwise adding o-methyl benzyl chloride with the purity of more than 99%, adding a quaternary ammonium salt catalyst, an alkali-binding agent and boric acid, controlling the temperature to be 30-100 ℃, carrying out heat preservation reaction, when the content of the o-methyl benzyl chloride is less than 0.1%, filling water into the container after the heat preservation reaction is finished, standing for 1-1.5 h, layering, and distilling to obtain the o-methyl benzyl cyanide.
6. The method of synthesizing 3-isochromone according to claim 5, wherein: the molar ratio of sodium cyanide to o-methylbenzyl chloride is 1.2: 1-1.2: 1.1, the mass ratio of the o-methyl benzyl chloride to the quaternary ammonium salt catalyst is 1: 0.004-1: 0.006, o-methylbenzyl chloride: alkali binding agent: the molar ratio of boric acid is 100: 0.5: 1; the quaternary ammonium salt catalyst is selected from any one of benzyltriethylammonium chloride, tetramethylammonium chloride, tetrabutylammonium bromide or octyltrimethylammonium chloride; the alkali binding agent is selected from zinc chloride, ferric trichloride or anhydrous aluminum trichloride.
7. The method of synthesizing 3-isochromone according to claim 1, wherein: adding 30% by mass of sodium hydroxide aqueous solution into a closed container, then adding o-tolylacetonitrile, heating to 95-103 ℃ for reflux, carrying out reflux heat preservation reaction for 6-8 h, and finishing the heat preservation reaction when the peak of the o-tolylacetonitrile is less than 0.1% after gas chromatographic analysis to reach a hydrolysis end point to obtain a hydrolysis product of the o-tolylsodium acetate; wherein, the ratio of sodium hydroxide: the molar ratio of the o-methyl phenylacetonitrile is 1.5: 1-1.5: 1.1.
8. The method of synthesizing 3-isochromone according to claim 1, wherein: and (4) regulating the pH value of the water layer of the hydrolyzed product of the sodium o-tolylacetate to 2-3 by using hydrochloric acid, separating out solids, cooling to below 20 ℃, centrifuging to obtain a wet product, and washing the acidity of the hydrochloric acid by using water during centrifugation to obtain the o-tolylacetic acid, wherein the hydrochloric acid is 30% in mass percentage.
9. The method of synthesizing 3-isochromone according to claim 1, wherein: adding o-tolylacetic acid and dichloroethane in a closed container, heating to 75-80 ℃, adding azobisisobutyronitrile, starting to introduce chlorine, stopping reaction until the content of the raw materials is 1% -5%, cooling and centrifuging to obtain 2-chloromethyl phenylacetic acid solid; wherein the mass ratio of the o-tolylacetic acid to the dichloroethane is 2: 1-2: 1.1, the mass ratio of o-tolylacetic acid to azobisisobutyronitrile is 10: 1-10: 1.1, the mass ratio of the o-tolylacetic acid to the chlorine is 1.8: 1-1.8: 1.1.
10. the method of synthesizing 3-isochromone according to claim 1, wherein: adding 2-chloromethyl phenylacetic acid solid and water into a closed container, heating to 50-60 ℃, then slowly adding sodium bicarbonate solid for hydrolysis reaction, stopping the reaction when the content of the 2-chloromethyl phenylacetic acid is below 0.3%, and drying to obtain 3-isochromanone solid after suction filtration, cyclohexane washing and water washing; wherein the mass ratio of the 2-chloromethyl phenylacetic acid solid to the water is 1: 3-1: 3.2, the mass ratio of the 2, 2-chloromethyl phenylacetic acid solid to the sodium bicarbonate solid is 2: 1-2: 1.1.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113912513A (en) * | 2021-11-19 | 2022-01-11 | 青岛恒宁生物科技有限公司 | Preparation method of oximido acetate compound and intermediate thereof |
| CN115772147A (en) * | 2022-12-23 | 2023-03-10 | 长沙钰腾新材料有限公司 | Method for synthesizing 3-isochromone or derivative thereof |
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| CN1222150A (en) * | 1996-06-17 | 1999-07-07 | 曾尼卡有限公司 | Process for preparing 3-isochromanone |
| EP1116720A1 (en) * | 1998-09-21 | 2001-07-18 | Showa Denko K.K. | Processes for the preparation of isochromanones and intermediates for the preparation thereof |
| CN1653058A (en) * | 2002-05-07 | 2005-08-10 | 辛根塔有限公司 | Process for the preparation of 3-isochromanone |
| CN105481722A (en) * | 2016-01-22 | 2016-04-13 | 江苏亚邦染料股份有限公司 | Preparation method of 1,4-diamido-2,3-dicyano anthraquinone |
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| EP1116720A1 (en) * | 1998-09-21 | 2001-07-18 | Showa Denko K.K. | Processes for the preparation of isochromanones and intermediates for the preparation thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113912513A (en) * | 2021-11-19 | 2022-01-11 | 青岛恒宁生物科技有限公司 | Preparation method of oximido acetate compound and intermediate thereof |
| CN113912513B (en) * | 2021-11-19 | 2024-01-26 | 青岛恒宁生物科技有限公司 | Preparation method of oximido acetate compound and intermediate thereof |
| CN115772147A (en) * | 2022-12-23 | 2023-03-10 | 长沙钰腾新材料有限公司 | Method for synthesizing 3-isochromone or derivative thereof |
| CN115772147B (en) * | 2022-12-23 | 2024-03-22 | 长沙钰腾新材料有限公司 | Synthesis method of 3-isochromone or derivative thereof |
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