CN102399159A - Synthesizing method of 3,5-dibromo-2-aminobenzaldehyde - Google Patents
Synthesizing method of 3,5-dibromo-2-aminobenzaldehyde Download PDFInfo
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- CN102399159A CN102399159A CN2011103716541A CN201110371654A CN102399159A CN 102399159 A CN102399159 A CN 102399159A CN 2011103716541 A CN2011103716541 A CN 2011103716541A CN 201110371654 A CN201110371654 A CN 201110371654A CN 102399159 A CN102399159 A CN 102399159A
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Abstract
The invention discloses a synthesizing method of 3,5-dibromo-2-aminobenzaldehyde which comprises the following steps of adding methyl 2-aminobenzoate and tribromide-N-methyl-N-butylimidazole in a reactor, agitating and heating the mixture until the mixture is dissolved, and then adding an intermediate 1, keeping the temperature at 60+/-2 DEG C, agitating the mixture for 2.5-3.5 hours, and then extracting, drying and condensing the mixture, obtaining an intermediate 2; adding absolute ethyl alcohol in the intermediate 2, cooling the mixture to 0 DEG C, and then adding NaBH3, controlling the temperature of the mixture no more than 5 DEG C, after finishing adding, cooling the mixture to 0 DEG C and performing an insulation reaction for 8-10 hours; after detecting the reaction is ended, slowly adding water in the reactant, agitating the reactant for 0.5-1 hour, filtering the reactant, condensing the filtrate to a dry state, heating and dissolving the filtrate with ethyl acetate, decoloring, filtering and cooling the mixture to separate out crystal, obtaining 3,5-dibromo-2-aminobenzaldehyde. The synthesizing method of the 3,5-dibromo-2-aminobenzaldehyde provided by the invention has the advantages of simple process and high yield, conditions are easy to control and industrialization production is easy to realize.
Description
Technical field
The present invention relates to the synthetic field of medicine intermediate, relate in particular to a kind of 3, the compound method of 5-two bromo-2-aminobenzaldehydes.
Background technology
3,5-two bromo-2-aminobenzaldehydes are a kind of widely used medicine intermediates, and its market consumption is big, has a extensive future.But in the prior art, 3,5-two bromo-2-aminobenzaldehydes synthetic exists complex process, step many, and yield is low, is generally about 40%, and is not easy to realize the shortcoming of suitability for industrialized production.
Summary of the invention
The present invention is just in order to overcome above-mentioned deficiency, and technical problem to be solved provides that a kind of technology is simple, yield is high, can realize a kind of 3 of suitability for industrialized production, the compound method of 5-two bromo-2-aminobenzaldehydes.
For solving the problems of the technologies described above, the technical scheme that the present invention adopted is following:
A kind of 3, the compound method of 5-two bromo-2-aminobenzaldehydes is characterized in that it comprises the steps:
(1) in reactor drum, adds 2-Methyl anthranilate, tribromide-N-methyl-N-normal-butyl imidazoles, be heated to dissolving while stirring, add midbody 1 then, keep 60 ± 2 ℃ to stir 2.5～3.5h, extraction then, dry, the concentrated midbody 2 that obtains;
(2) in midbody 2, add absolute ethyl alcohol, be cooled to 0 ℃, add NaBH then
3, controlled temperature is no more than 5 ℃, finishes, and is cooled to 0 ℃ of insulation reaction 8～10h, and detection reaction finishes; Slowly add entry, stir 0.5～1h, filter, filtrating is concentrated into dried, use the ETHYLE ACETATE heating for dissolving; Decolouring is filtered, and crystal is separated out in cooling, obtains 3,5-two bromo-2-aminobenzaldehydes;
Wherein, the chemical formula of said midbody 1 is:
The chemical formula of said midbody 2 is:
The mass ratio of said 2-Methyl anthranilate and midbody 1 is preferably: 3: 3～5.
The volume ratio of the quality of said 2-Methyl anthranilate and tribromide-N-methyl-N-normal-butyl imidazoles is preferably 3: 8～and 12.
Said midbody 2 and NaBH
3Mass ratio be: 1: 0.2～0.6.
Beneficial effect: of the present invention 3, the compound method of 5-two bromo-2-aminobenzaldehydes, technology is simple, and yield is high, and condition is easy to control, is easy to realize suitability for industrialized production.
Embodiment
Embodiment 1
In the 500mL there-necked flask, add 15g 2-Methyl anthranilate (SM1); Add 50mL tribromide-N-methyl-N-normal-butyl imidazoles then; Be heated to 60 ℃ of dissolvings while stirring; Add 19g midbody 1 (tribromide-N-methyl-N-normal-butyl imidazoles) then, keep 60 ℃ to stir 3h, the TLC detection reaction finishes; Add ether 150mL*3 then, stir extraction, combined ether layer is used anhydrous Na
2SO
4Drying, filtering Na
2SO
4, ether layer is evaporated to dried, obtain 25g midbody 2 (5,6-two bromo-2-amino-oil of Niobe), yield 81.6%.
In the 500mL there-necked flask, add 25g midbody 2 (5,6-two bromo-2-amino-oil of Niobe) and 250mL anhydrous methanols, be cooled to 0 ℃, slowly add NaBH then
39g, controlled temperature are no more than 5 ℃; After adding finishes, 0 ℃ of insulation reaction 8h, the TLC detection reaction finishes; Slowly add 10mL water then, stir 30min, filter, filtrating is concentrated into dried, with 50mL ETHYLE ACETATE heating for dissolving, activated carbon decolorizing, the filtering gac, cooling crystallization obtains 3,5-two bromo-2-aminobenzaldehyde solid 17g, yield 75%.
Embodiment 2
In the 500mL there-necked flask, add 24g 2-Methyl anthranilate (SM1); Add 64mL tribromide-N-methyl-N-normal-butyl imidazoles then; Be heated to 60 ℃ of dissolvings while stirring; Add 25g midbody 1 (tribromide-N-methyl-N-normal-butyl imidazoles) then, keep 60 ℃ to stir 3h, the TLC detection reaction finishes; Add ether 150mL*3 then, stir extraction, combined ether layer is used anhydrous Na
2SO
4Drying, filtering Na
2SO
4, ether layer is evaporated to dried, obtain 38g midbody 2 (5,6-two bromo-2-amino-oil of Niobe), yield 77%.
In the 500mL there-necked flask, add 33g midbody 2 (5,6-two bromo-2-amino-oil of Niobe) and 250mL anhydrous methanols, be cooled to 0 ℃, slowly add NaBH316.6g then, controlled temperature is no more than 5 ℃; After adding finishes, 0 ℃ of insulation reaction 8h, the TLC detection reaction finishes; Slowly add 10mL water then, stir 30min, filter, filtrating is concentrated into dried, with 50mL ETHYLE ACETATE heating for dissolving, activated carbon decolorizing, the filtering gac, cooling crystallization obtains 3,5-two bromo-2-aminobenzaldehyde solid 21.8g, yield 73%.
Embodiment 3
In the 500mL there-necked flask, add 42g 2-Methyl anthranilate (SM1); Add 144mL tribromide-N-methyl-N-normal-butyl imidazoles then; Be heated to 60 ℃ of dissolvings while stirring; Add 60g midbody 1 (tribromide-N-methyl-N-normal-butyl imidazoles) then, keep 60 ℃ to stir 3h, the TLC detection reaction finishes; Add ether 150mL*3 then, stir extraction, combined ether layer is used anhydrous Na
2SO
4Drying, filtering Na
2SO
4, ether layer is evaporated to dried, obtain 69g midbody 2 (5,6-two bromo-2-amino-oil of Niobe), yield 75%.
In the 500mL there-necked flask, add 69g midbody 2 (5,6-two bromo-2-amino-oil of Niobe) and 250mL anhydrous methanols, be cooled to 0 ℃, slowly add NaBH then
341.4g controlled temperature is no more than 5 ℃; After adding finishes, 0 ℃ of insulation reaction 8h, the TLC detection reaction finishes; Slowly add 10mL water then, stir 30min, filter, filtrating is concentrated into dried, with 50mL ETHYLE ACETATE heating for dissolving, activated carbon decolorizing, the filtering gac, cooling crystallization obtains 3,5-two bromo-2-aminobenzaldehyde solid 45g, yield 72%.
The foregoing description does not limit the present invention in any way, and every employing is equal to the technical scheme that replacement or the mode of equivalent transformation obtain and all drops in protection scope of the present invention.
Claims (4)
1. one kind 3, the compound method of 5-two bromo-2-aminobenzaldehydes is characterized in that it comprises the steps:
(1) in reactor drum, adds 2-Methyl anthranilate, tribromide-N-methyl-N-normal-butyl imidazoles, be heated to dissolving while stirring, add midbody 1 then, keep 60 ± 2 ℃ to stir 2.5～3.5h, extraction then, dry, the concentrated midbody 2 that obtains;
(2) in midbody 2, add absolute ethyl alcohol, be cooled to 0 ℃, add NaBH then
3, controlled temperature is no more than 5 ℃, finishes, and is cooled to 0 ℃ of insulation reaction 8～10h, and detection reaction finishes; Slowly add entry, stir 0.5～1h, filter, filtrating is concentrated into dried, use the ETHYLE ACETATE heating for dissolving; Decolouring is filtered, and crystal is separated out in cooling, obtains 3,5-two bromo-2-aminobenzaldehydes;
Wherein, the chemical formula of said midbody 1 is:
The chemical formula of said midbody 2 is:
2. according to claim 1 a kind of 3, the compound method of 5-two bromo-2-aminobenzaldehydes is characterized in that the mass ratio of said 2-Methyl anthranilate and midbody 1 is: 3: 3～5.
3. according to claim 1 a kind of 3, the compound method of 5-two bromo-2-aminobenzaldehydes is characterized in that the quality of said 2-Methyl anthranilate and the volume ratio of tribromide-N-methyl-N-normal-butyl imidazoles are 3: 8～12.
4. according to claim 1 a kind of 3, the compound method of 5-two bromo-2-aminobenzaldehydes is characterized in that said midbody 2 and NaBH
3Mass ratio be: 1: 0.2～0.6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103716541A CN102399159A (en) | 2011-11-22 | 2011-11-22 | Synthesizing method of 3,5-dibromo-2-aminobenzaldehyde |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103716541A CN102399159A (en) | 2011-11-22 | 2011-11-22 | Synthesizing method of 3,5-dibromo-2-aminobenzaldehyde |
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| CN102399159A true CN102399159A (en) | 2012-04-04 |
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|---|---|---|---|
| CN2011103716541A Pending CN102399159A (en) | 2011-11-22 | 2011-11-22 | Synthesizing method of 3,5-dibromo-2-aminobenzaldehyde |
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Application publication date: 20120404 |