CN107652193A - A kind of production method of 2 amino to toluene acetophenone hydrochloride - Google Patents
A kind of production method of 2 amino to toluene acetophenone hydrochloride Download PDFInfo
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- CN107652193A CN107652193A CN201710997030.8A CN201710997030A CN107652193A CN 107652193 A CN107652193 A CN 107652193A CN 201710997030 A CN201710997030 A CN 201710997030A CN 107652193 A CN107652193 A CN 107652193A
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- toluene
- chloros
- ethyl ketone
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of 2 amino to the production method of toluene acetophenone hydrochloride, comprise the following steps：1st, production of 2 chloros to toluene ethyl ketone toluene：2nd, production of 2 chloros to toluene ethyl ketone hexamethylenetetramine ammonium salt；3rd, production of 2 amino to toluene acetophenone hydrochloride.This method production technology is relatively easy, and working condition is simple and easy to control, easy to operate, and production cost is low.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of producer of 2- amino to toluene acetophenone hydrochloride
Method.
Background technology
2- amino mainly has following several production methods to the important intermediate that toluene acetophenone hydrochloride is medical agricultural chemicals：
1st, first use to toluene ethyl ketone bromination, obtain 2- bromos to toluene ethyl ketone (see JP61152637, CN101723912,
CN101709056), then with 2- bromos to toluene ethyl ketone and diformamide base sodium and Sodium azide (NaN3) react to synthesize 2-
Amino needs hydrogenating reduction, operates ratio to toluene ethyl ketone (see US20050113283, US2003062392), the second step of the route
It is more complicated；
2nd, using toluene and chloracetyl chloride it is acylated 2- chloros to toluene ethyl ketone (see WO2008125014,
CN101928253)；Then 2- bromos to toluene ethyl ketone or 2- chloros to toluene ethyl ketone and phthalic amide ammonolysis, then hydrazinolysis,
2- amino is obtained to toluene acetophenone hydrochloride.
Comparing above two production method, second of production method is preferable, and second method technique is simple, and cost is low, but
The a large amount of ammonium chlorides of by-product and the alchlor aqueous solution, environmental pollution are larger.
The content of the invention
In order to solve the above-mentioned problems of the prior art, the invention provides a kind of 2- amino to toluene acetophenone hydrochloride
Production method, this method production technology is relatively easy, and working condition is simple and easy to control, and easy to operate, production cost is low.
Technical scheme is used by realizing above-mentioned purpose of the present invention：
A kind of 2- amino comprises the following steps to the production method of toluene acetophenone hydrochloride：
1st, production of the 2- chloros to toluene ethyl ketone toluene：
Under nitrogen protection, in toluene, 0~10 DEG C is cooled under stirring, adds aluminum trichloride (anhydrous) and chloracetyl chloride,
The mol ratio of chloracetyl chloride and aluminum trichloride (anhydrous) is 1:1~1.5,45~55 DEG C are warming up to after dripping, continues stirring reaction 1
~2h, backflow is then warming up to, continues 3~4h of backflow, after backflow terminates, mole of hydrochloric acid and water, water and chloracetyl chloride is added dropwise
Than for 4~5h, being warming up to 45~55 DEG C of 0.5~1.5h of hydrolysis, stop stratification after nitrogen protection, separation, organic layer water
Agitator treating, stratification, separation, organic layer add Anhydrous potassium carbonate, stir, and filtering, obtain 2- chloros to toluene ethyl ketone first
Benzole soln；
2nd, production of the 2- chloros to toluene ethyl ketone hexamethylenetetramine ammonium salt：
To the 2- chloros obtained by step 1 to adding hexamethylenetetramine, six first in toluene ethyl ketone toluene solution under stirring
The mol ratio of urotropine and chloracetyl chloride is 1:0.95~1.05,1.5~2.5h is stirred at 35~40 DEG C, is centrifuged, filtering,
Filter cake, dry, obtain 2- chloros to toluene ethyl ketone hexamethylenetetramine ammonium salt；
3rd, production of the 2- amino to toluene acetophenone hydrochloride：
Under 2- chloros from stirring to step 2 to adding hydrochloric acid and solvent methanol in toluene ethyl ketone hexamethylenetetramine ammonium salt,
Backflow is warming up to, flow back 1.5~2.5h, and after backflow terminates, first normal pressure fractionates out the azeotropic mixture of formal and water, then
Normal pressure fractionates out methanol, to kettle temperature up to 100 DEG C, keeps kettle temperature constant, starts to be evaporated under reduced pressure, it is 0.09MPa to be decompressed to vacuum
When, methanol eddy dissolving is added, precipitation is cooled to and is precipitated to completely, centrifugal filtration, filtrate is evaporated under reduced pressure to kettle temperature again and reached
100 DEG C, vacuum reach 0.08MPa, distill to after dry, add ethyl acetate backflow, while stirring is cooled to precipitation and has been precipitated to
Entirely, filter, wash, dry, obtain 2- amino to toluene acetophenone hydrochloride.
Further, in step 1.1, control below 30 DEG C of temperature, aluminum trichloride (anhydrous) is first slowly added under stirring, is then controlled
Below 40 DEG C of temperature processed, chloracetyl chloride is slowly added dropwise.
Further, in step 1.1, the separating obtained water layer of stratification twice is added into storage tank and mixed, for reclaiming profit
With.
Compared with prior art, the advantages of the present invention are：
1st, the present invention uses cheap raw material, and high income (60.9%, in terms of chloro-acetyl chloride), cost is low.
2nd, the three wastes overwhelming majority caused by the present invention recycles, and such as alchlor and ammonium chloride, is reclaimed
Utilize, reduce the pollution to environment, and can be sold as byproduct, add income.
3rd, the production method technique is relatively easy, and working condition is simple and easy to control, is suitable for industrialization large-scale production.
Embodiment
With reference to embodiment, the present invention is described in detail.
Embodiment 1
1st, production of the 2- chloros to toluene ethyl ketone toluene：
In 10m3In glassed steel reaction vessels, 4500L toluene is put into, under nitrogen protection, 10 DEG C are cooled under stirring, control
Below 30 DEG C of temperature in reactor, first stir one bag of bag and add 590kg aluminum trichloride (anhydrous)s, then control the temperature of reactor
Below 40 DEG C, lower dropwise addition 500kg chloracetyl chlorides are stirred, 50 DEG C are warming up to after dripping, continues stirring reaction 2h, then heats up
To backflow, continue the 4h that flows back, after backflow terminates, 250kg32wt% hydrochloric acid and 340kg water is added dropwise, is warming up to 50 DEG C, after hydrolyzing 1h
Stop nitrogen protection, then stratification 1h, separation, water layer is concentration about 50wt% alchlors, is entered storage tank and is returned
Receive and utilize, organic layer 100L water agitator treatings, stand 1h, layering, water layer, which enters storage tank and mixed with water layer above, to be reclaimed
Utilizing, sell for synthesized polymer aluminium chloride, organic layer adds 100kg Anhydrous potassium carbonate powder, and 40 DEG C are stirred 2 hours, filtering,
2- chloros are obtained to toluene ethyl ketone toluene solution.
Structural formula of the 2- chloros to toluene ethyl ketone toluene：
2nd, production of the 2- chloros to toluene ethyl ketone hexamethylenetetramine ammonium salt：
In a kettle, the 2- chloros of step 1 are added under stirring into reactor to toluene ethyl ketone toluene solution and 590kg
Hexamethylenetetramine, 2h is stirred at 40 DEG C, centrifuged, filtering, 1000L toluene washing filter cake, filter cake depressurized at 80 DEG C and done
It is dry, 1093kg2- chloros are obtained to toluene ethyl ketone hexamethylenetetramine ammonium salt, purity 98%, yield 80%.
2- chloros are to the structural formula of toluene ethyl ketone hexamethylenetetramine ammonium salt：
3rd, production of the 2- amino to toluene acetophenone hydrochloride：
In 10m3In glassed steel reaction vessels, 1750kg32wt% hydrochloric acid and 3500kg methanol are added, next bag of bag of stirring adds
Enter 2- chloros caused by step 2 to toluene ethyl ketone hexamethylenetetramine ammonium salt, backflow is warming up to after adding, flow back 2h, backflow knot
Shu Hou, first normal pressure fractionate out the azeotropic mixture of formal and water, and then normal pressure fractionates out methanol, to kettle temperature up to 100 DEG C, protect
It is constant to hold kettle temperature, starts to be evaporated under reduced pressure, it is 0.09MPa to be decompressed to vacuum, starts stirring difficulty, changes reflux, is added dropwise
1000kg methanol, after 2h is dissolved in backflow, 20 DEG C are cooled to, precipitation is precipitated to completely, and centrifugal filtration, filter cake is ammonium chloride, will be filtered
Liquid is evaporated under reduced pressure again reaches 0.08MPa to kettle temperature up to 100 DEG C, vacuum, distills to doing, changes reflux again, is added dropwise
1300kg ethyl acetate, stirring cool to 20 DEG C, and precipitation is precipitated to completely, filtering, filter cake is washed 2 times with 100L ethyl acetate,
Filter cake is dried under reduced pressure at 80 DEG C, 500kg2- amino is obtained to toluene acetophenone hydrochloride, mp220 DEG C, purity 98.5%, receives
Rate 76.1%.
2- amino is to the structural formula of toluene acetophenone hydrochloride：
Claims (3)
1. a kind of 2- amino is to the production method of toluene acetophenone hydrochloride, it is characterised in that comprises the following steps：
1.1st, production of the 2- chloros to toluene ethyl ketone toluene：
Under nitrogen protection, in toluene, 0~10 DEG C is cooled under stirring, adds aluminum trichloride (anhydrous) and chloracetyl chloride, chloroethene
The mol ratio of acyl chlorides and aluminum trichloride (anhydrous) is 1:1~1.5, be warming up to 45~55 DEG C after dripping, continue stirring reaction 1~
2h, backflow is then warming up to, continues 3~4h of backflow, after backflow terminates, the mol ratio of hydrochloric acid and water, water and chloracetyl chloride is added dropwise
For 4~5h, 45~55 DEG C of 0.5~1.5h of hydrolysis are warming up to, stop stratification after nitrogen protection, separation, organic layer is stirred with water
Washing is mixed, stratification, separation, organic layer addition Anhydrous potassium carbonate, stirs, filtering, obtains 2- chloros to toluene ethyl ketone toluene
Solution；
1.2nd, production of the 2- chloros to toluene ethyl ketone hexamethylenetetramine ammonium salt：
To the 2- chloros obtained by step 1 to adding hexamethylenetetramine, six methines four in toluene ethyl ketone toluene solution under stirring
The mol ratio of amine and chloracetyl chloride is 1:0.95~1.05,1.5~2.5h is stirred at 35~40 DEG C, is centrifuged, filtering, filter cake,
Dry, obtain 2- chloros to toluene ethyl ketone hexamethylenetetramine ammonium salt；
1.3rd, production of the 2- amino to toluene acetophenone hydrochloride：
Under 2- chloros from stirring to step 2 to adding hydrochloric acid and solvent methanol, heating in toluene ethyl ketone hexamethylenetetramine ammonium salt
To backflow, flow back 1.5~2.5h, and after backflow terminates, first normal pressure fractionates out the azeotropic mixture of formal and water, then normal pressure
Methanol is fractionated out, to kettle temperature up to 100 DEG C, keeps kettle temperature constant, starts to be evaporated under reduced pressure, when to be decompressed to vacuum be 0.09MPa, add
Enter methanol eddy dissolving, be cooled to precipitation and be precipitated to completely, centrifugal filtration, filtrate is evaporated under reduced pressure again to kettle temperature up to 100 DEG C,
Vacuum reaches 0.08MPa, distills to after doing, and adds ethyl acetate backflow, while stirring is cooled to precipitation and is precipitated to completely, mistake
Filter, wash, dry, obtain 2- amino to toluene acetophenone hydrochloride.
2. 2- amino according to claim 1 is to the production method of toluene acetophenone hydrochloride, it is characterised in that：Step 1.1
In, control below 30 DEG C of temperature, aluminum trichloride (anhydrous) is first slowly added under stirring, then control below 40 DEG C of temperature, slowly drop
Chlorination chloroacetic chloride.
3. 2- amino according to claim 1 is to the production method of toluene acetophenone hydrochloride, it is characterised in that：Step 1.1
In, the separating obtained water layer of stratification twice is added into storage tank and mixed, for recycling.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710997030.8A CN107652193A (en) | 2017-10-20 | 2017-10-20 | A kind of production method of 2 amino to toluene acetophenone hydrochloride |
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| CN201710997030.8A CN107652193A (en) | 2017-10-20 | 2017-10-20 | A kind of production method of 2 amino to toluene acetophenone hydrochloride |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101636397B (en) * | 2007-04-13 | 2012-06-13 | 中国人民解放军军事医学科学院毒物药物研究所 | Urea compounds, preparation methods and pharmaceutical uses thereof |
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2017
- 2017-10-20 CN CN201710997030.8A patent/CN107652193A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101636397B (en) * | 2007-04-13 | 2012-06-13 | 中国人民解放军军事医学科学院毒物药物研究所 | Urea compounds, preparation methods and pharmaceutical uses thereof |
Non-Patent Citations (1)
| Title |
|---|
| CHATE AV 等: "Efficient approach to thiazolidinones via a one-pot three-component reaction involving 2-amino-1-phenylethanone hydrochloride, aldehyde and mercaptoacetic acid", 《CHINESE JOURNAL OF CATALYSIS》 * |
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Application publication date: 20180202 |