CN110015963A - A kind of preparation method of the chloro- 6- methylaniline of 2- - Google Patents
A kind of preparation method of the chloro- 6- methylaniline of 2- Download PDFInfo
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- CN110015963A CN110015963A CN201910293050.6A CN201910293050A CN110015963A CN 110015963 A CN110015963 A CN 110015963A CN 201910293050 A CN201910293050 A CN 201910293050A CN 110015963 A CN110015963 A CN 110015963A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
- C07C303/22—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof from sulfonic acids, by reactions not involving the formation of sulfo or halosulfonyl groups; from sulfonic halides by reactions not involving the formation of halosulfonyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/32—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/45—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
- C07C309/48—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton the carbon skeleton being further substituted by halogen atoms
Abstract
The present invention relates to chemical fields, more particularly to a kind of preparation method of the chloro- 6- methylaniline of high-purity 2-.The present invention provides a kind of preparation method of chloro- 6- methylaniline of 2-, comprising: under the conditions of by 4- amino -3- toluenesulfonic acid and acetic anhydride existing for the acid binding agent, prepares 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate；Chlorination reaction is carried out under the conditions of by 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate existing for the chlorination reagent, prepares the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2-；The chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2- is subjected to decarboxylic reaction, prepares the chloro- 6- methylaniline of 2-.In preparation method provided by the present invention, by amido protecting, chlorination, decarboxylic reaction, and specific sulfone class solvent is used, reduced the generation of side reaction in the reaction, waste liquid is nontoxic, and operation and post-processing approach are simple.
Description
Technical field
The present invention relates to chemical fields, more particularly to a kind of preparation method of the chloro- 6- methylaniline of high-purity 2-.
Background technique
The chloro- 6- methylaniline of 2- is a kind of medicine intermediate that synthesis is important up to husky aniline anticarcinogen.The chloro- 6- first of 2- at present
The synthetic method of base aniline is seldom reported, and the synthesis of similar compound uses special catalyst more, is passed through more malicious chlorine and does
Chlorination reaction, with decarboxylation under relatively hazardous gelled acid high temperature, complicated for operation, environmental pollution is big, and yield is difficult to ensure.
Summary of the invention
In view of the foregoing deficiencies of prior art, the purpose of the present invention is to provide a kind of chloro- 6- methyl of high-purity 2-
The preparation method of aniline, for solving the problems of the prior art.
In order to achieve the above objects and other related objects, the present invention provides a kind of preparation method of chloro- 6- methylaniline of 2-,
Include:
1) under the conditions of by 4- amino -3- toluenesulfonic acid and acetic anhydride existing for the acid binding agent, 4- acetyl ammonia is prepared
Base -3- Sodium Toluene Sulphonate；
2) chlorination reaction is carried out under the conditions of by 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate existing for the chlorination reagent, is prepared
Obtain the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2-；
3) the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2- is subjected to decarboxylic reaction, prepares the chloro- 6- methylaniline of 2-.
In some embodiments of the present invention, in the step 1), mole of acetic anhydride and 4- amino -3- toluenesulfonic acid
Than for 0.1~2.0:1.
In some embodiments of the present invention, in the step 1), reaction carries out in the presence of a solvent.
In some embodiments of the present invention, in the step 1), reaction temperature is 0~60 DEG C.
In some embodiments of the present invention, in the step 1), solvent is selected from one of water, sodium hydrate aqueous solution
Or a variety of combination.
In some embodiments of the present invention, in the step 1), the post-processing of reaction includes: concentration.
In some embodiments of the present invention, in the step 2), the chlorination reagent be selected from hydrochloric acid-oxidizer system,
One of hydrochloric acid-zinc chloride system or a variety of combinations.
In some embodiments of the present invention, in the step 2), reaction carries out in the presence of a solvent.
In some embodiments of the present invention, in the step 2), reaction temperature is 20~60 DEG C.
In some embodiments of the present invention, in the step 2), in the step 2), reaction dissolvent is selected from acetic acid, salt
One of acid, sulfuric acid or a variety of combinations；
In some embodiments of the present invention, in the step 2), reaction temperature is 40~50 DEG C.
In some embodiments of the present invention, in the step 2), according to the molar ratio, the usage amount of hydrochloric acid is 4- acetyl ammonia
0.5~20.0 times of base -3- Sodium Toluene Sulphonate is measured, H in hydrogen peroxide2O2Amount be 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate
0.5~10.0 times of amount.
In some embodiments of the present invention, in the step 2), according to the molar ratio, the usage amount of hydrochloric acid is 4- acetyl ammonia
0.5~20.0 times of amount of base -3- Sodium Toluene Sulphonate, the usage amount of zinc chloride is 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate
0.5~2.0 times of amount.
In some embodiments of the present invention, in the step 2), the post-processing of chlorination reaction includes: that reducing agent is added to break
Bad system oxidisability, concentration.
In some embodiments of the present invention, in the step 3), decarboxylic reaction carries out in acid condition.
In some embodiments of the present invention, in the step 3), decarboxylic reaction carries out in the presence of a solvent.
In some embodiments of the present invention, in the step 3), reaction temperature is 100~150 DEG C.
In some embodiments of the present invention, in the step 3), acid condition that decarboxylic reaction is 0.5~5.0 in pH
Lower progress.
In some embodiments of the present invention, in the step 3), the solvent is selected from sulfone class solvent, is preferably selected from ring fourth
One of sulfone, dimethyl sulfoxide, dimethyl sulfone or a variety of combinations.
In some embodiments of the present invention, in the step 3), reaction temperature is 110~130 DEG C.
In some embodiments of the present invention, in the step 3), the post-processing of decarboxylic reaction includes the following steps: cold
But, pH is adjusted to neutrality, is extracted, product is precipitated in organic phase, and the product being precipitated is dissociated again.
Detailed description of the invention
Fig. 1 is shown as analysis result schematic diagram of the embodiment of the present invention.
Specific embodiment
Inventor passes through a large amount of explorative experiments, provides a kind of preparation method of new chloro- 6- methylaniline of 2-,
The chloro- 6- methylaniline of 2- that the preparation method can prepare high-purity by the preparation method of clean and effective has very
Good industrialization prospect, completes the present invention on this basis.
First aspect present invention provides a kind of preparation method of chloro- 6- methylaniline of 2-, comprising:
Under the conditions of by 4- amino -3- toluenesulfonic acid and acetic anhydride existing for the acid binding agent, 4- acetylaminohydroxyphenylarsonic acid is prepared
3- Sodium Toluene Sulphonate；
Chlorination reaction is carried out under the conditions of by 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate existing for the chlorination reagent, preparation obtains
Obtain the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2-；
The chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2- is subjected to decarboxylic reaction, prepares the chloro- 6- methylaniline of 2-.
Preparation method provided by the present invention may include: that the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2- is carried out decarboxylation
Reaction, prepares the chloro- 6- methylaniline of 2-, reaction equation is as follows:
Decarboxylic reaction provided by the present invention usually carries out in acid condition, for example, it may be pH be 0.5~5.0,
0.5~1.0,1.0~2.0,2.0~3.0,3.0~4.0 or 4.0~5.0 acid condition.Those skilled in the art may be selected
Suitable acid is used to provide the described acid condition, for example, it may be HCl, acetic acid etc..
In decarboxylic reaction provided by the present invention, the decarboxylic reaction can usually carry out in the presence of a solvent,
The solvent is usually the good solvent of reaction system, and the boiling point of the solvent is usually less than reaction temperature, for example, decarboxylic reaction
In solvent can be with high boiling sulfone class solvent, it is contour specifically to can be such as sulfolane, dimethyl sulfoxide, dimethyl sulfone
Boiling point solvent.The dosage of suitable solvent may be selected for decarboxylic reaction, for example, solvent in decarboxylic reaction in those skilled in the art
Dosage can be 1.0~10 times of reaction raw materials amounts, for example, 1~10mL solvent can be used for 1 gram of reaction raw materials.
In decarboxylic reaction provided by the present invention, decarboxylic reaction usually requires to be performed under heating conditions, for example, reaction can
To carry out under conditions of 100~150 DEG C, reaction can also carry out under conditions of 110~130 DEG C.Those skilled in the art
The reaction time can be adjusted according to reaction process, for example, can be judged by the methods of TLC, chromatography the reaction of decarboxylic reaction into
Journey, for another example the reaction time of decarboxylic reaction can be 5~30,5~10,10~20 or 20~30 hours.
In chlorination reaction provided by the present invention, it is anti-to decarboxylation that suitable post-processing approach may be selected in those skilled in the art
The product answered is post-processed, for example, the post-processing of decarboxylic reaction may include steps of: it is cooling, pH is adjusted to neutrality, extraction
It takes, product is precipitated in organic phase, and the product being precipitated is dissociated again, can be obtained target product.It is preferably implemented in the present invention one
In example, the pH value that sodium hydroxide (aqueous solution) adjusts reaction system can be used, the solvent that when extraction uses can be alkyl halide
Hydrocarbon solvent (for example, methylene chloride etc.).In another preferred embodiment of the present invention, the method for dissociation, which can be, is dissolved in product
In the water of appropriate pH condition, extraction removes solvent.
Preparation method provided by the present invention can also include: to try 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate in chlorination
Chlorination reaction is carried out under the conditions of agent is existing, prepares the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2-, reaction equation is such as
Under:
In chlorination reaction provided by the present invention, the chlorination reagent is typically used to provide the chlorine source in chlorination reaction, from
And chlorination can be carried out to phenyl ring to prepare the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2-.The chlorination reagent can be hydrochloric acid
With the mixed system of oxidant, for example, it may be hydrochloric acid-hydrogen peroxide system etc., the chlorination reagent is also possible to hydrochloric acid and chlorine
Change the mixed system of zinc, for example, it may be hydrochloric acid-zinc chloride system etc. (Lucas reagent), so as to pass through relatively mild item
Part generates chlorine source by amount.In the chlorination reagent, the usage amount of hydrochloric acid and oxidant generally depends on the demand in chlorine source, usually
For, according to the molar ratio, the usage amount of hydrochloric acid can be 0.5~20 times of amount, 0.5 of 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate
~1 times of amount, 1~2 times of amount, 2~3 times of amounts, 3~4 times of amounts, 4~5 times of amounts, 5~10 times of amounts, 10~15 times of amounts or 15~20 times
It measures, H in hydrogen peroxide2O2Amount can be 0.5~10.0 times of 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate amount, 0.1~0.5 times
Amount, 0.5~1 times of amount, 1~1.5 times of amount, 1.5~2 times of amounts, 2~2.5 times of amounts, 2.5~3,3~5 or 5~10 times of amounts, it is described double
The concentration of oxygen water usually can be 20~38wt%.In the chlorination reagent, the usage amount of hydrochloric acid and zinc chloride is generally depended on
The demand in chlorine source, usually, according to the molar ratio, the usage amount of hydrochloric acid can be 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate
0.5~20.0 times amount, 1.0~2 times amount, 2~4 times amount, 4~6 times amount, 6~8 times amount, 8~10 times amount, 10~15 times amount or
15~20 times of amounts, zinc chloride is usually anhydrous zinc chloride, and the usage amount of zinc chloride can be 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid
0.5~2.0 times of sodium amount, 0.1~0.5 times of amount, 0.5~1 times of amount, 1~2 times of amount, 2~3 times of amounts, 3~4 times of amounts, 4~5 times of amounts,
5~10 times of amounts, 10~15 times of amounts or 15~20 times of amounts.When forming hydrochloric acid and hydrogen peroxide system or hydrochloric acid-zinc chloride system,
Hydrogen peroxide or zinc chloride can be usually added by amount and include in the reaction system of hydrochloric acid and substance, for example, can using be added dropwise,
The modes such as it is added portionwise, to avoid the generation of side reaction.
In chlorination reaction provided by the present invention, reaction can usually carry out in the presence of a solvent, anti-to promote
It answers and makes reaction system that there is good dissolubility.In a preferred embodiment of the invention, for hydrochloric acid and hydrogen peroxide system
As the chlorination reaction of chlorination reagent, can using acetic acid, sulfuric acid, (usually concentrated hydrochloric acid is specifically as follows mass fraction to hydrochloric acid
Aqueous hydrochloric acid solution not less than 20%) etc. be used as solvent, while as solvent, also there is catalytic action to reaction.This
The dosage of suitable solvent may be selected for chlorination reaction in field technical staff, for example, the dosage of solvent can be in chlorination reaction
5~30 times for reaction raw materials are measured, for example, 5~30mL solvent can be used for 1 gram of reaction raw materials.
In chlorination reaction provided by the present invention, chlorination reaction usually can be in room temperature to the temperature strip of reaction dissolvent boiling point
Carried out under part, for example, reaction can be carried out under conditions of 20~60 DEG C, reaction can also under conditions of 40~50 DEG C into
Row.Those skilled in the art can adjust the reaction time according to reaction process, for example, can be judged by the methods of TLC, chromatography
The reaction process of chlorination reaction, for another example the reaction time of chlorination reaction can be 1~30 hour, 1~2 hour, it is 2~3 small
When, 3~4 hours, 4~6 hours, 6~10 hours, 10~20 hours or 20~30 hours.
In chlorination reaction provided by the present invention, it is anti-to chlorination that suitable post-processing approach may be selected in those skilled in the art
The product answered is post-processed, for example, the post-processing of chlorination reaction may include steps of: reducing agent is added and destroys system oxygen
Product directly can be used for subsequent reactions after removing appropriate solvent by the property changed, concentration.
Preparation method provided by the present invention can also include: that 4- amino -3- toluenesulfonic acid and acetic anhydride are being tied up acid
Under the conditions of agent is existing, 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate is prepared, reaction equation is as follows:
In amido protecting reaction provided by the present invention, acetic anhydride carries out amido protecting reaction as protecting group.Acetic anhydride
Usage amount be usually for 4- amino -3- toluenesulfonic acid match, for example, press molar amount, acetic anhydride with
The molar ratio of 4- amino -3- toluenesulfonic acid can be 0.1~2.0:1, preferably can be 0.1~0.1.2:1, more preferably can be with
For 0.1~0.7:1.
In amido protecting reaction provided by the present invention, reaction can usually carry out in the presence of a solvent, described
Solvent usually can be the good solvent of reaction system, for example, to can be water, sodium hydroxide water-soluble for the solvent in amido protecting reaction
Liquid one of liquid alkaline etc. or a variety of combinations.The dosage that suitable solvent may be selected in those skilled in the art is protected for amino
Shield reaction, for example, the dosage of solvent can be 1~10 times of amount of reaction raw materials in amido protecting reaction, for example, anti-for 1 gram
Raw material is answered, 1~10mL solvent can be used.
In amido protecting provided by the present invention reaction, reaction usually carries out at a lower temperature, for example, reacting can be
It is carried out under conditions of 0~60 DEG C, 0~20 DEG C, 20~40 DEG C or 40~60 DEG C.Those skilled in the art can be according to reaction process
Adjust the reaction time, for example, can by TLC, chromatography, the methods of judge amido protecting react reaction process, for another example
The reaction time of amido protecting reaction can be 0.5~24,0.5~1,1~2,2~4,4~6,6~12 or 12~24 hour.
In amido protecting reaction provided by the present invention, suitable post-processing approach is may be selected to ammonia in those skilled in the art
The product of base protection reaction is post-processed, for example, the post-processing of amido protecting reaction may include steps of: concentration,
After removing appropriate solvent, product directly can be used for subsequent reactions.
The preparation method that second aspect of the present invention provides the chloro- 6- methylaniline of 2- provided by first aspect present invention is being made
Purposes in the standby chloro- 6- methylaniline of 2-.
In the preparation method of the chloro- 6- methylaniline of 2- provided by the present invention, by amido protecting, chlorination, decarboxylic reaction,
And specific sulfone class solvent has been used, reduce the generation of side reaction in the reaction, waste liquid is nontoxic, operation and rear place
Reason method is simple, to provide a kind of preparation method of efficient, environmentally friendly, low-cost chloro- 6- methylaniline of 2-, has very
Good industrialization prospect.
Illustrate embodiments of the present invention below by way of specific specific example, those skilled in the art can be by this specification
Other advantages and efficacy of the present invention can be easily understood for disclosed content.The present invention can also pass through in addition different specific realities
The mode of applying is embodied or practiced, the various details in this specification can also based on different viewpoints and application, without departing from
Various modifications or alterations are carried out under spirit of the invention.
It should be clear that in the following example not specifically dated process equipment or device be all made of conventional equipment in the art or
Device.
In addition, it should also be understood that, one or more method and step mentioned in the present invention does not repel before and after the combination step
It can also be inserted into other methods step there may also be other methods step or between these explicitly mentioned steps, unless separately
It is described；It should also be understood that the combination connection relationship between one or more equipment/device mentioned in the present invention is not repelled
The two equipment/devices specifically mentioned before and after the unit equipment/device there may also be other equipment/device or at these it
Between can also be inserted into other equipment/device, unless otherwise indicated.Moreover, unless otherwise indicated, the number of various method steps is only
Identify the convenient tool of various method steps, rather than for the arrangement order of limitation various method steps or limits the enforceable model of the present invention
It encloses, relativeness is altered or modified, and without material changes in technical content, when being also considered as, the present invention is enforceable
Scope.
Embodiment 1
The synthesis of 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate:
40g 4- amino -3- toluenesulfonic acid, water 240g, hydrogen-oxygen are added in the three-necked flask equipped with blender thermometer
Change sodium 8.6g and acetic anhydride 26.2g, is cooled to 50 DEG C, makes raw material fully reacting within insulation reaction 2 hours.It depressurizes after reaction dense
It is reduced to dry, obtains product 55g, yield 100%, 98% or more HPLC purity.
Embodiment 2
The synthesis of the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2-:
55g 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate, acetic acid are added in the three-necked flask equipped with blender thermometer
150g, concentrated hydrochloric acid 87.1g control 30% couple of hydrogen water 47.4g of 40-50 DEG C of temperature dropwise addition, make within completion of dropwise addition insulation reaction 3-4 hours
Raw material fully reacting.Sodium hydrogensulfite is added after reaction and destroys system oxidisability, is concentrated to dryness, obtains product 57g, receive
Rate is that 98.78%, HPLC purity is 96% or more.
Embodiment 3
The synthesis of the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2-:
109g 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate, acetic acid are added in the three-necked flask equipped with blender thermometer
297g, concentrated hydrochloric acid 172g control 30% couple of hydrogen water 94g of 40-50 DEG C of temperature dropwise addition, make original within completion of dropwise addition insulation reaction 3-4 hours
Expect fully reacting.Sodium hydrogensulfite is added after reaction and destroys system oxidisability, is concentrated to dryness to obtain product 115g, yield
It is 96% or more for 100%, HPLC purity.
Embodiment 4
The synthesis of the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2-:
670g 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate, acetic acid are added in the three-necked flask equipped with blender thermometer
1828.5g, concentrated hydrochloric acid 1059.8g control 40-50 DEG C of temperature dropwise addition 30% couple of hydrogen water 577.5g, completion of dropwise addition insulation reaction 3-4
Hour makes raw material fully reacting.Sodium hydrogensulfite is added after reaction and destroys system oxidisability, is concentrated to dryness to obtain product
705g, yield 100%, HPLC purity are 96.21%.
Embodiment 5
The chloro- 6- methylaniline synthesis of 2-:
The chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid 115g of 2-, ring are added in the three-necked flask equipped with blender thermometer
Fourth sulfone 434g, concentrated hydrochloric acid 106g are warming up to 120 DEG C of reaction 26h, and reaction terminates, and 25 DEG C of addition water 575g are cooled to, with 30% hydrogen
Sodium oxide molybdena adjusts ph=7, static layering, and water phase extracts primary, anhydrous sodium sulfate 20g drying, suction filtration with methylene chloride, and filtrate adds
Enter in 30% acidic alcohol (58g), stir 2h, be cooled to -5 DEG C of stirring 1h, filter, 0.6 times of water dilution is added in filter cake, is added dropwise
30% sodium hydroxide adjusts ph=7 and methylene chloride 100g is added, and active carbon 3g stirs 0.5h, filters, filtrate static layering, water phase
Methylene chloride extracts primary, merging methylene chloride, anhydrous sodium sulfate drying, and filtrate first uses level-one lobe pump at 25-30 DEG C of water temperature
(remarks: thickening temperature height will lead to product colour and deepen), concentration, then it is adjusted to three-level, GC is surveyed in sampling until methylene chloride disappears.
Claret liquid: 37g is taken, product yield 60%, testing result is as shown in Figure 1, product purity is 99.7%.
In conclusion the present invention effectively overcomes various shortcoming in the prior art and has high industrial utilization value.
The above-described embodiments merely illustrate the principles and effects of the present invention, and is not intended to limit the present invention.It is any ripe
The personage for knowing this technology all without departing from the spirit and scope of the present invention, carries out modifications and changes to above-described embodiment.Cause
This, institute is complete without departing from the spirit and technical ideas disclosed in the present invention by those of ordinary skill in the art such as
At all equivalent modifications or change, should be covered by the claims of the present invention.
Claims (10)
1. a kind of preparation method of the chloro- 6- methylaniline of 2-, comprising:
1) under the conditions of by 4- amino -3- toluenesulfonic acid and acetic anhydride existing for the acid binding agent, 4- acetylaminohydroxyphenylarsonic acid 3- is prepared
Sodium Toluene Sulphonate；
2) chlorination reaction is carried out under the conditions of by 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate existing for the chlorination reagent, is prepared
The chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2-；
3) the chloro- 4- acetylaminohydroxyphenylarsonic acid 3- toluenesulfonic acid of 2- is subjected to decarboxylic reaction, prepares the chloro- 6- methylaniline of 2-.
2. the preparation method of the chloro- 6- methylaniline of 2- as described in claim 1, which is characterized in that in the step 1), acetic acid
The molar ratio of acid anhydride and 4- amino -3- toluenesulfonic acid is 0.1~2.0:1；
And/or in the step 1), reaction carries out in the presence of a solvent；
And/or in the step 1), reaction temperature is 0~60 DEG C.
3. the preparation method of the chloro- 6- methylaniline of 2- as claimed in claim 2, which is characterized in that in the step 1), solvent
Selected from one of water, sodium hydrate aqueous solution or a variety of combinations.
4. the preparation method of the chloro- 6- methylaniline of 2- as described in claim 1, which is characterized in that in the step 1), reaction
Post-processing include: concentration.
5. the preparation method of the chloro- 6- methylaniline of 2- as described in claim 1, which is characterized in that described in the step 2)
Chlorination reagent is selected from one of hydrochloric acid-oxidizer system, hydrochloric acid-zinc chloride system or a variety of combinations；
And/or in the step 2), reaction carries out in the presence of a solvent；
And/or in the step 2), reaction temperature is 20~60 DEG C.
6. the preparation method of the chloro- 6- methylaniline of 2- as claimed in claim 5, which is characterized in that described in the step 2)
In step 2), reaction dissolvent is selected from one of acetic acid, hydrochloric acid, sulfuric acid or a variety of combinations；
And/or in the step 2), reaction temperature is 40~50 DEG C；
And/or in the step 2), according to the molar ratio, the usage amount of hydrochloric acid is 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate
0.5~20.0 times is measured, H in hydrogen peroxide2O2Amount be 0.5~10.0 times of 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate amount；
And/or in the step 2), according to the molar ratio, the usage amount of hydrochloric acid is 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate
0.5~20.0 times of amount, the usage amount of zinc chloride are 0.5~2.0 times of amounts of 4- acetylaminohydroxyphenylarsonic acid 3- Sodium Toluene Sulphonate.
7. the preparation method of the chloro- 6- methylaniline of 2- as described in claim 1, which is characterized in that in the step 2), chlorination
The post-processing of reaction includes: that reducing agent is added to destroy system oxidisability, concentration.
8. the preparation method of the chloro- 6- methylaniline of 2- as described in claim 1, which is characterized in that in the step 3), decarboxylation
Reaction carries out in acid condition；
And/or in the step 3), decarboxylic reaction carries out in the presence of a solvent；
And/or in the step 3), reaction temperature is 100~150 DEG C.
9. the preparation method of the chloro- 6- methylaniline of 2- as claimed in claim 8, which is characterized in that in the step 3), decarboxylation
It reacts and is carried out in the case where pH is 0.5~5.0 acid condition；
And/or in the step 3), the solvent is selected from sulfone class solvent, is preferably selected from sulfolane, dimethyl sulfoxide, dimethyl sulfone
One of or a variety of combinations；
And/or in the step 3), reaction temperature is 110~130 DEG C.
10. the preparation method of the chloro- 6- methylaniline of 2- as described in claim 1, which is characterized in that in the step 3), take off
The post-processing of carboxylic reaction includes the following steps: to cool down, and adjusts pH to neutrality, extraction, organic phase precipitation product, the product being precipitated
It is dissociated again.
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