CN109456295A - The microchannel method synthesis technology of 3- isochromanome - Google Patents
The microchannel method synthesis technology of 3- isochromanome Download PDFInfo
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- CN109456295A CN109456295A CN201811511061.9A CN201811511061A CN109456295A CN 109456295 A CN109456295 A CN 109456295A CN 201811511061 A CN201811511061 A CN 201811511061A CN 109456295 A CN109456295 A CN 109456295A
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- isochromanome
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
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Abstract
The invention discloses a kind of microchannel method synthesis technologies of 3- isochromanome, reaction step is as follows: 1) using o-Tolylacetic acid as raw material, at a suitable temperature and in suitable solvent, using microchannel reaction technology, o-chloromethyl acetic acid is prepared by chlorinating agent of sulfonic acid chloride；2) synthesize o-chloromethyl acetic acid it is not purified, suitable alkali and at a temperature of, cyclization obtains 3- isochromanome.By the above-mentioned means, the present invention can high yield, high-purity, controllable production o-chloromethyl acetic acid, the latter then can smoothly produce target product 3- isochromanome under alkaline condition.
Description
Technical field
The present invention relates to medicine, pesticide intermediate production technology field, more particularly to 3- isochromanome
Microchannel method synthesis technology.
Background technique
Methoxy acrylic bactericide is in recent years emerging a kind of fungicide, have wide spectrum, efficiently, interior suction, low toxicity,
Advantages of environment protection, market demand are continuously increased, and have new product to occur successively；Such product is needed using the different benzo of 3- more
Dihydro pyrone is essential important intermediate, therefore market is to 3- as the upstream compound for synthesizing its active group
The demand of isochromanome is also to be continuously increased.
There are many ways to synthesizing 3- isochromanome, but the factors such as cost of material and product yield can give birth to it
Production impacts, therefore selects suitable raw material and production technology for the industrialized production of realization 3- isochromanome
It is most important.Currently, the technique that mass production uses is mostly that it is anti-to carry out methyl chloride generation by chlorine using o-Tolylacetic acid as raw material
O-chloromethyl acetic acid should be generated, then under alkaline condition cyclization at 3- isochromanome；But o-Tolylacetic acid
Chlorination belong to radical reaction comprising chain causes, chain growth and chain termination three phases, and during which methyl is through a chlorine
Chlorination still can be carried out again after generation, more chloro side reactions is caused to occur, and by-product increases, and eventually results in product 3-
Isochromanome yield is not high, purity is low.
There are extraordinary market prospects in view of 3- isochromanome, neighbour can be limited by developing the new technique of one kind
More chloro side reactions of methylphenyl acetic acid, it will be able to improve product 3- isochromanome yield and purity, it will generate
Good Social benefit and economic benefit, this is significantly.
Summary of the invention
The invention mainly solves the technical problem of providing a kind of microchannel methods of 3- isochromanome to synthesize work
Skill, can high yield, high-purity, controllable production o-chloromethyl acetic acid, the latter then can smoothly produce mesh under alkaline condition
Mark product 3- isochromanome.
In order to solve the above technical problems, one technical scheme adopted by the invention is that:
A kind of microchannel method synthesis technology of 3- isochromanome is provided, production process route is as follows:
1) using o-Tolylacetic acid as raw material, at a suitable temperature and in suitable solvent, skill is answered using microchannel plate
O-chloromethyl acetic acid is prepared by chlorinating agent of sulfonic acid chloride in art；
2) synthesize o-chloromethyl acetic acid it is not purified, suitable alkali and at a temperature of, cyclization obtains the different benzene of 3-
And dihydro pyrone.
In a preferred embodiment of the present invention, temperature is 80~120 DEG C in step 1).
In a preferred embodiment of the present invention, the solvent used in the step 1) for methylene chloride, chloroform,
One of benzene, toluene, chlorobenzene, o-dichlorohenzene, 1,2- dichloroethanes, tetrachloro-ethylene or a variety of mixtures.
In a preferred embodiment of the present invention, the molal weight of o-Tolylacetic acid and sulfonic acid chloride ratio is in step 1)
1:1~2.
In a preferred embodiment of the present invention, the temperature range in step 2) is 40~100 DEG C.
In a preferred embodiment of the present invention, the temperature range in step 2) is 50~80 DEG C.
In a preferred embodiment of the present invention, the alkali used in step 2) is sodium hydroxide, potassium hydroxide, hydroxide
One of lithium, cesium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, saleratus or a variety of mixtures.
In a preferred embodiment of the present invention, in the cyclization system of step 2), the range of pH value is maintained at 7.5
~8.5.
The beneficial effects of the present invention are: the microchannel method synthesis technology of 3- isochromanome of the present invention, can limit
More chloro side reactions of o-Tolylacetic acid processed improve product 3- isochromanome yield and purity, can in high yield,
High-purity, controllable production o-chloromethyl acetic acid, the latter then can smoothly produce the different benzo of target product 3- under alkaline condition
Dihydro pyrone.
Detailed description of the invention
Fig. 1 is the nuclear magnetic spectrum using the 3- isochromanome product of the synthetic method production in the present invention.
Specific embodiment
The preferred embodiments of the present invention will be described in detail below so that advantages and features of the invention can be easier to by
It will be appreciated by those skilled in the art that so as to make a clearer definition of the protection scope of the present invention.
A kind of microchannel method synthesis technology of 3- isochromanome, production process route are as follows:
1) using o-Tolylacetic acid as raw material, 80~120 DEG C at a temperature of and suitable solvent in, use microchannel plate
Technology is answered, o-chloromethyl acetic acid is prepared by chlorinating agent of sulfonic acid chloride；Wherein, used solvent be methylene chloride,
One of chloroform, benzene, toluene, chlorobenzene, o-dichlorohenzene, 1,2- dichloroethanes, tetrachloro-ethylene or a variety of mixtures；It is adjacent
The molal weight of methylphenyl acetic acid and sulfonic acid chloride ratio is 1:1~2；In this step, temperature ranges preferably from 100~120 DEG C.
2) synthesize o-chloromethyl acetic acid it is not purified, in suitable alkali, 40~100 DEG C at a temperature of, cyclisation
Reaction obtains 3- isochromanome；The alkali used is sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium hydroxide, carbonic acid
One of sodium, sodium bicarbonate, potassium carbonate, saleratus or a variety of mixtures, wherein it is preferred that using lithium hydroxide, carbonic acid
Sodium, sodium bicarbonate, potassium carbonate, saleratus；In this step, reaction temperature is preferably 50~80 DEG C, in cyclization system,
The range of pH value is maintained at 7.5~8.5.
Embodiment 1:
50 grams of o-Tolylacetic acids and 50 grams of sulfonic acid chlorides are each configured to 250 milliliters of chlorobenzene solution, and microchannel plate is arranged
Answering device temperature is 80 DEG C, is reacted the chlorobenzene solution input micro passage reaction of two raw materials with the flow velocity of 5mL/min；It will
After reaction solution is collected, cold water be washed once, and is adjusted pH~8 with 20% liquid alkaline, is kept the temperature 60 DEG C of reactions, HPLC detection reaction system without
Variation is washed using 100 milliliters, and organic phase is dry, and concentration removes solvent, and residue is recrystallized using methanol, filters, does
It is dry to obtain 18 grams of 3- isochromanomes, yield 36%, purity 99.1%, 1HNMR (CDCl3,400MHz) δ: 3.72 (s,
2H,CH2),5.32(s,2H,CH2),7.22-7.35(m,4H,ArH)。
Embodiment 2:
50 grams of o-Tolylacetic acids and 50 grams of sulfonic acid chlorides are each configured to 250 milliliters of chlorobenzene solution, and microchannel plate is arranged
Answering device temperature is 90 DEG C, is reacted the chlorobenzene solution input micro passage reaction of two raw materials with the flow velocity of 5mL/min；It will
After reaction solution is collected, cold water be washed once, and adjust pH~8 with 10% wet chemical, keep the temperature 60 DEG C of reactions, and HPLC detection is anti-
It answers system unchanged, is washed using 100 milliliters, organic phase is dry, and concentration removes solvent, and residue is tied again using methanol
Crystalline substance filters, is dried to obtain 24 grams of 3- isochromanomes, yield 49%, purity 99.2%.
Embodiment 3:
50 grams of o-Tolylacetic acids and 50 grams of sulfonic acid chlorides are each configured to 250 milliliters of chlorobenzene solution, and microchannel plate is arranged
Answering device temperature is 120 DEG C, is reacted the chlorobenzene solution input micro passage reaction of two raw materials with the flow velocity of 5mL/min；
After reaction solution is collected, cold water be washed once, and is adjusted pH~7.5 with saturated sodium bicarbonate aqueous solution, is kept the temperature 50 DEG C of reactions, HPLC
It is unchanged to detect reaction system, is washed using 100 milliliters, organic phase is dry, and concentration removes solvent, and residue is carried out using methanol
Recrystallization, filters, is dried to obtain 36 grams of 3- isochromanomes, yield 73%, purity 99.5%.
Embodiment 4:
50 grams of o-Tolylacetic acids and 50 grams of sulfonic acid chlorides are each configured to 250 milliliters of o-dichlorobenzene solution, are arranged micro- logical
Road temperature of reactor is 120 DEG C, with the flow velocity of 5mL/min by the o-dichlorobenzene solution of two raw materials input micro passage reaction into
Row reaction；After reaction solution is collected, cold water be washed once, and adjust pH~7.5 with saturated potassium hydrogen carbonate aqueous solution, keep the temperature 80 DEG C instead
It answers, HPLC detection reaction system is unchanged, is washed using 100 milliliters, and organic phase is dry, and concentration removes solvent, residue use
Methanol is recrystallized, and is filtered, is dried to obtain 30 grams of 3- isochromanomes, yield 61%, purity 99.4%.
Embodiment 5:
50 grams of o-Tolylacetic acids and 50 grams of sulfonic acid chlorides are each configured to 250 milliliters of tetrachloro-ethylene solution, are arranged micro- logical
Road temperature of reactor is 120 DEG C, with the flow velocity of 5mL/min by the tetrachloro-ethylene solution of two raw materials input micro passage reaction into
Row reaction；After reaction solution is collected, cold water be washed once, and adjust pH~7.2 with saturated potassium hydrogen carbonate aqueous solution, keep the temperature 50 DEG C instead
It answers, HPLC detection reaction system is unchanged, is washed using 100 milliliters, and organic phase is dry, and concentration removes solvent, residue use
Methanol is recrystallized, and is filtered, is dried to obtain 39 grams of 3- isochromanomes, yield 79%, purity 99.5%.
The above description is only an embodiment of the present invention, is not intended to limit the scope of the invention, all to utilize this hair
Equivalent structure or equivalent flow shift made by bright specification and accompanying drawing content is applied directly or indirectly in other relevant skills
Art field, is included within the scope of the present invention.
Claims (8)
1. a kind of microchannel method synthesis technology of 3- isochromanome, which is characterized in that production process route is as follows:
1) using o-Tolylacetic acid as raw material, at a suitable temperature and in suitable solvent, using microchannel reaction technology, with
Sulfonic acid chloride is that o-chloromethyl acetic acid is prepared in chlorinating agent；
2) synthesize o-chloromethyl acetic acid it is not purified, suitable alkali and at a temperature of, cyclization obtains the different benzo two of 3-
Hydrogen pyranone.
2. the microchannel method synthesis technology of 3- isochromanome according to claim 1, which is characterized in that in step
It is rapid 1) in temperature be 80~120 DEG C.
3. the microchannel method synthesis technology of 3- isochromanome according to claim 1, which is characterized in that in step
Rapid 1) the middle solvent used is methylene chloride, chloroform, benzene, toluene, chlorobenzene, o-dichlorohenzene, 1,2- dichloroethanes, four
One of vinyl chloride or a variety of mixtures.
4. the microchannel method synthesis technology of 3- isochromanome according to claim 1, which is characterized in that in step
It is rapid 1) in the molal weight of o-Tolylacetic acid and sulfonic acid chloride ratio be 1:1~2.
5. the microchannel method synthesis technology of 3- isochromanome according to claim 1, which is characterized in that in step
It is rapid 2) in temperature range be 40~100 DEG C.
6. the microchannel method synthesis technology of 3- isochromanome according to claim 5, which is characterized in that in step
It is rapid 2) in temperature range be 50~80 DEG C.
7. the microchannel method synthesis technology of 3- isochromanome according to claim 1, which is characterized in that in step
It is rapid 2) used in alkali be sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, carbon
One of potassium hydrogen phthalate or a variety of mixtures.
8. the microchannel method synthesis technology of 3- isochromanome according to claim 1, which is characterized in that in step
In rapid cyclization system 2), the range of pH value is maintained at 7.5~8.5.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1222150A (en) * | 1996-06-17 | 1999-07-07 | 曾尼卡有限公司 | Process for preparing 3-isochromanone |
| CN102796039A (en) * | 2012-08-16 | 2012-11-28 | 浙江工业大学 | Method for continuous preparation of 2-chloro-5-chloromethylpyridine in microchannel |
-
2018
- 2018-12-11 CN CN201811511061.9A patent/CN109456295B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1222150A (en) * | 1996-06-17 | 1999-07-07 | 曾尼卡有限公司 | Process for preparing 3-isochromanone |
| CN102796039A (en) * | 2012-08-16 | 2012-11-28 | 浙江工业大学 | Method for continuous preparation of 2-chloro-5-chloromethylpyridine in microchannel |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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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