CN116462628A - Preparation method and application of 2-bromo-5-aminopyridine - Google Patents
Preparation method and application of 2-bromo-5-aminopyridine Download PDFInfo
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- CN116462628A CN116462628A CN202210031971.7A CN202210031971A CN116462628A CN 116462628 A CN116462628 A CN 116462628A CN 202210031971 A CN202210031971 A CN 202210031971A CN 116462628 A CN116462628 A CN 116462628A
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- aminopyridine
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- XTHKRYHULUJQHN-UHFFFAOYSA-N 6-bromopyridin-3-amine Chemical compound NC1=CC=C(Br)N=C1 XTHKRYHULUJQHN-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- CRTOIQFRVBJJRI-UHFFFAOYSA-N 2,6-dibromopyridin-3-amine Chemical compound NC1=CC=C(Br)N=C1Br CRTOIQFRVBJJRI-UHFFFAOYSA-N 0.000 claims abstract description 31
- 238000006722 reduction reaction Methods 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 40
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 claims description 30
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000006227 byproduct Substances 0.000 claims description 11
- 239000003638 chemical reducing agent Substances 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
- -1 pyridine compound Chemical class 0.000 claims description 9
- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical compound [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- 239000000758 substrate Substances 0.000 claims description 6
- HKDVVTLISGIPFE-UHFFFAOYSA-N 2-bromopyridin-3-amine Chemical compound NC1=CC=CN=C1Br HKDVVTLISGIPFE-UHFFFAOYSA-N 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000004973 liquid crystal related substance Substances 0.000 claims description 3
- 239000000575 pesticide Substances 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 8
- 239000012065 filter cake Substances 0.000 description 7
- 238000005070 sampling Methods 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 238000005893 bromination reaction Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 230000031709 bromination Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000007256 debromination reaction Methods 0.000 description 3
- 238000009413 insulation Methods 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- HUUFTVUBFFESEN-UHFFFAOYSA-N 2-bromo-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)N=C1 HUUFTVUBFFESEN-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 238000012797 qualification Methods 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- PTEFNEALEPSHLC-UHFFFAOYSA-N 6-bromopyridin-3-ol Chemical compound OC1=CC=C(Br)N=C1 PTEFNEALEPSHLC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a preparation method and application of 2-bromo-5-aminopyridine. The method removes bromine on 2, 6-dibromo-3-aminopyridine through a reduction reaction to obtain 2-bromo-5-aminopyridine. The invention provides a novel method for preparing 2-bromo-5-aminopyridine, which has the advantages of low cost, high yield, safety and high efficiency and is suitable for industrial production.
Description
Technical Field
The invention belongs to the field of material chemistry, and particularly relates to a preparation method and application of 2-bromo-5-aminopyridine.
Background
2-bromo-5-aminopyridine is an important intermediate, and can be used for synthesis of pesticides, medicines and liquid crystal materials. The main synthetic route of 2-bromo-5-aminopyridine is shown below.
Patent WO9846605 proposes that 2-bromo-5-nitropyridine is used as a raw material, acetic acid water is used as a solvent, iron powder is added in batches for reduction, quenching is carried out, and extraction and concentration are carried out to obtain the product 2-bromo-5-aminopyridine with the yield of 98.0%. The raw material 2-bromo-5-nitropyridine is not easy to obtain, and the reduction three wastes of the iron powder are large. Is not suitable for industrialized amplified production.
Industrial & Engineering Chemistry Research (2011), 50 (21), 12271-12275 propose that 3-aminopyridine is used as a raw material, acetonitrile is used as a solvent, a sodium bromide/sodium bromate mixture is used as a brominating reagent, molar equivalent of sodium bromide is 0.67, molar equivalent of sodium bromate is 0.34, cooling is carried out to 5-10 ℃, sulfuric acid is added dropwise for reaction, and then quenching, extraction, drying, concentration and silica gel column separation are carried out, so that the product 2-bromo-5-aminopyridine is obtained, and the yield is 83%.
The university of western traffic document Synthetic Communications (2019), 49 (11), 1406-1415 proposes bromination using 3-aminopyridine as a starting material, ethanol as a solvent, and a copper bromide/tetrabutylammonium bromide mixture as a brominating reagent in a yield of 65%.
Patent CN102199152 proposes that 3-aminopyridine be used as raw material, acetonitrile be used as solvent, and N-bromosuccinimide (NBS) be used as brominating reagent in a yield of 20.2%.
In india document Tetrahedron Letters (2007) 6951-6953, it is proposed to prepare 2, 6-dibromo-3-aminopyridine in a yield of 95% by brominating NBS at 0 ℃ using 3-aminopyridine as a raw material and N, N-Dimethylformamide (DMF) as a solvent.
The 3-aminopyridine is used as a raw material, and the yield of the direct synthesis of the 2-bromo-5-aminopyridine is low, the selectivity is poor, so that the searching of the preparation method of the 2-bromo-5-aminopyridine which is simple in operation and suitable for industrial production is a technical problem which needs to be solved urgently at present.
Disclosure of Invention
In view of at least one of the above problems, the present invention provides a method for preparing 2-bromo-5-aminopyridine. The method removes bromine on 2, 6-dibromo-3-aminopyridine through a reduction reaction to obtain 2-bromo-5-aminopyridine.
In some embodiments, the reducing agent employed in the reduction reaction is selected from one or more of zinc metal, hydrogen, ammonium formate.
Further, the metallic zinc is powdered as zinc powder.
In some embodiments, the reducing agent employed in the reduction reaction is zinc powder; the addition equivalent of zinc powder as a reducing agent is 1.0 to 1.5 times the equivalent of 2, 6-dibromo-3-aminopyridine as a substrate.
In some embodiments, the catalyst employed in the reduction reaction is selected from one or more of sodium hydroxide, potassium carbonate, palladium on charcoal, platinum on charcoal. Preferably, the catalyst is sodium hydroxide or palladium on charcoal.
In some embodiments, 2, 6-dibromo-3-aminopyridine is debrominated using a reducing agent in the presence of a first solvent and a catalyst to yield the product 2-bromo-5-aminopyridine.
In some embodiments, the first solvent is selected from one or more of water, acetonitrile, ethanol, tetrahydrofuran.
In some embodiments, the reaction temperature of the reduction reaction is 20 to 100 ℃. Preferably, the reaction temperature of the reduction reaction is 40 to 70 ℃.
In some embodiments, 2, 6-dibromo-3-aminopyridine is synthesized by reacting a pyridine compound with a brominating reagent; the brominating reagent is selected from one or more of sodium bromide and sodium bromate; the pyridine compound is selected from one or more of 3-aminopyridine, 2-bromo-5-aminopyridine and 2-bromo-3-aminopyridine.
In some embodiments, the reaction temperature for the synthesis of 2, 6-dibromo-3-aminopyridine is from 0 to 10 ℃; adding concentrated sulfuric acid into the mixed solution of the pyridine compound and the brominating reagent at the synthetic reaction temperature; the adding equivalent of the concentrated sulfuric acid is 1.0-2.0 times of the equivalent of the brominating reagent; the brominating reagent is sodium bromide and sodium bromate; the solvent of the mixed solution is water. Further, concentrated sulfuric acid was added by dropwise addition. The main function of concentrated sulfuric acid is to react sodium bromate with sodium bromide to form bromine for bromination.
In some embodiments, the pyridine compound is derived, in part or in whole, from a debrominated byproduct of the reduction reaction. The debrominated by-products include 3-aminopyridine and/or 2-bromo-3-aminopyridine.
On the other hand, the invention provides the application of the 2-bromo-5-aminopyridine synthesized by the preparation method in pesticides, medicines and liquid crystal materials.
The synthetic route of the invention is as follows:
the preparation of 2-bromo-5-aminopyridine by reduction debromination using 2, 6-dibromo-3-aminopyridine as a raw material has not been reported in the literature. The invention provides a new process route for preparing 2-bromo-5-aminopyridine. The 3-aminopyridine is taken as a raw material, 2, 6-dibromo-3-aminopyridine is obtained through bromination, then the 2-bromo-5-aminopyridine is prepared through selective debromination by a reducing agent, and debrominated byproducts (3-aminopyridine and/or 2-bromo-3-aminopyridine) can be recycled to the first step for re-bromination. The 3-aminopyridine is used as a raw material, the 2-bromo-5-aminopyridine is obtained in high yield by a stepwise method, the bromination of the pyridine compound in the first step has no selectivity problem, and the debromination byproduct 3-aminopyridine and 2-bromo-3-aminopyridine obtained in the second step can be recycled. Therefore, the invention has the characteristics of low cost, high yield, safety and high efficiency, and is suitable for industrial production.
Detailed Description
The invention is further described in connection with specific embodiments in order to provide a better understanding of the technical means, inventive features, objectives and efficacy of the invention. The present invention is not limited to the following examples.
Example 1: preparation of 2, 6-dibromo-3-aminopyridine
50g (0.53 mol) of 3-aminopyridine, 200g of water, 73.9g (0.71 mol) of sodium bromide and 55.0g (0.69 mol) of sodium bromate are put into a reaction bottle, the temperature is reduced to 0-10 ℃, 161.1g (1.83 mol) of concentrated sulfuric acid is added dropwise, the reaction is carried out for 2 hours after the dropwise addition, sampling and detection are carried out, filtration is carried out after qualified, a filter cake is washed by water, and then dried to obtain 132.5g of a dry product with the purity of 98% and the yield of 98%.
Example 2: preparation of 2, 6-dibromo-3-aminopyridine
400g of 2-bromo-5-aminopyridine crystallization mother liquor (containing 10g (0.11 mol) of 3-aminopyridine, 5g (0.03 mol) of 2-bromo-5-aminopyridine and 5g (0.05 mol) of sodium bromide), 37.5g (0.394 mol) of fresh 3-aminopyridine, 68.2g (0.66 mol) of sodium bromide, 55.0g (0.69 mol) of sodium bromate, cooling to 0-10 ℃, dropwise adding 161.1g (1.83 mol) of concentrated sulfuric acid, after dropwise adding, preserving heat for 2 hours, sampling and detecting, filtering after passing, washing a filter cake with water, and drying to obtain a dry product 131.2, wherein the purity is 99%, and the yield is 98%.
Example 3: preparation of 2-bromo-5-aminopyridine
50g (0.2 mol) of 2, 6-dibromo-3-aminopyridine, 150g of ethanol, 133.0g (1.0 mol) of 30% NaOH solution, heating to 70-75 ℃, adding 15.6g (0.24 mol) of zinc powder into the system in batches, carrying out thermal insulation reaction for 3 hours after the addition, sampling and detecting, cooling to 20-30 ℃ after passing, layering, extracting an alkali layer by ethanol, merging ethanol layers, concentrating, adding water to replace the ethanol, neutralizing pH by hydrochloric acid to Ph=5-8, cooling, crystallizing, filtering, washing a filter cake, drying to obtain 28.2g of 2-bromo-5-aminopyridine dry product, wherein the purity is more than or equal to 98.0%, and the single-pass yield: 81.2 percent, the loss of filtrate and the byproduct account for about 15.5 percent, and the mixture is applied to the preparation of the 2, 6-dibromo-3-aminopyridine.
Example 4: preparation of 2-bromo-5-aminopyridine
50g (0.2 mol) of 2, 6-dibromo-3-aminopyridine, 150g of ethanol, 187g (1.0 mol) of 30% KOH solution, heating to 40-50 ℃, adding 15.6g (0.24 mol) of zinc powder into the system in batches, carrying out thermal insulation reaction for 3 hours after the addition, sampling and detecting, cooling to 20-30 ℃ after the qualification, layering, extracting an alkali layer by ethanol, merging ethanol layers, concentrating, adding water to replace the ethanol, neutralizing pH by hydrochloric acid to Ph=5-8, cooling and crystallizing, filtering, washing and drying a filter cake to obtain 25.8g of 2-bromo-5-aminopyridine dry product, wherein the purity is more than or equal to 97.0%, and the yield: 73.5 percent, the loss of filtrate and the byproduct account for about 20.5 percent, and the mixture is applied to the preparation of the 2, 6-dibromo-3-aminopyridine.
Example 5: preparation of 2-bromo-5-aminopyridine
50g (0.2 mol) of 2, 6-dibromo-3-aminopyridine, 250g of ethanol, 1.0g of palladium-charcoal and 63.1g (1.0 mol) of ammonium formate are put into a reaction bottle, the temperature is raised to 40-50 ℃, the temperature is kept for reaction for 20 hours, sampling and detection are carried out, after the reaction is qualified, the temperature is reduced to room temperature, a catalyst is filtered, filtrate is distilled, ethanol is replaced by water, the replacement is completed, the temperature is reduced and crystallization is carried out, the filtration, the filter cake is washed and dried, and 14.7g of 2-bromo-5-aminopyridine with the purity of more than or equal to 98.0 percent is obtained, and the yield is: 42%. The loss of the filtrate and the byproduct account for about 54.2 percent, and the filtrate is used for preparing the 2, 6-dibromo-3-aminopyridine.
Example 6: preparation of 2-bromo-5-aminopyridine
50g (0.2 mol) of 2, 6-dibromo-3-aminopyridine, 250g of ethanol, 1.0g of 10% platinum carbon, 3 times of nitrogen replacement, heating to 50-50 ℃, introducing hydrogen, 5-6 bar of pressure, preserving heat for reaction for 5 hours, sampling and detecting, cooling to room temperature after qualification, filtering a catalyst, distilling filtrate, replacing ethanol with water, cooling and crystallizing after replacement, filtering, washing a filter cake, and drying to obtain 18.3g of 2-bromo-5-aminopyridine, wherein the purity is more than or equal to 98.0%, and the yield is more than or equal to 98.0 percent: 52.8%. The loss of the filtrate and the byproduct account for about 34.2 percent, and the filtrate is used for preparing the 2, 6-dibromo-3-aminopyridine.
Example 7: preparation of 2-bromo-5-aminopyridine
50g (0.2 mol) of 2, 6-dibromo-3-aminopyridine, 150g of ethanol, 133.0g (1.0 mol) of 30% NaOH solution, heating to 70-75 ℃, adding 20.8g (0.32 mol) of zinc powder into the system in batches, carrying out thermal insulation reaction for 3 hours after the addition, sampling and detecting, cooling to 20-30 ℃ after passing, layering, extracting an alkali layer by ethanol, merging ethanol layers, concentrating, adding water to replace the ethanol, neutralizing pH by hydrochloric acid to Ph=5-8, cooling, crystallizing, filtering, washing a filter cake, drying to obtain 15.9g of 2-bromo-5-aminopyridine dry product, wherein the purity is more than or equal to 98.0%, and the single-pass yield: 45.6 percent, the loss of filtrate and the byproduct account for about 37.5 percent, and the mixture is applied to the preparation of the 2, 6-dibromo-3-aminopyridine.
Example 8
Otherwise, the same as in example 3 was conducted except that the amount of zinc powder charged was 11.7g (0.18 mol). The raw materials are 10 percent of the rest, the unreacted raw materials are complete, 26.5g of 2-bromo-5-hydroxypyridine dry product is about 85 percent of purity, the single pass yield is 66.0 percent, the filtrate loss and the byproduct account for about 20 percent, and the 2, 6-dibromo-3-aminopyridine is used for preparing the catalyst.
Examples 3 and 7 differ in the presence of only zinc powder added during the preparation, 0.24mol and 0.32mol respectively, i.e. equivalent ratios of 0.2mol to the substrate 2, 6-dibromo-3-aminopyridine of 1.2:1 and 1.6:1 respectively. This indicates that when the equivalent ratio of reducing agent to substrate 2, 6-dibromo-3-aminopyridine is too large, a significant drop in single pass yield occurs.
Examples 3 and 8 differ in the presence of only zinc powder added during the preparation, 0.24mol and 0.18mol respectively, i.e. equivalent ratios of 0.2mol to the substrate 2, 6-dibromo-3-aminopyridine of 1.2:1 and 0.9:1 respectively. This indicates that when the equivalent ratio of the reducing agent to the substrate 2, 6-dibromo-3-aminopyridine is too small, the raw material reaction is incomplete, the product purity is poor, and the yield is low.
The foregoing describes in detail preferred embodiments of the present invention. It should be understood that numerous modifications and variations can be made in accordance with the concepts of the invention without requiring creative effort by one of ordinary skill in the art. Therefore, all technical solutions which can be obtained by logic analysis, reasoning or limited experiments based on the prior art by the person skilled in the art according to the inventive concept shall be within the scope of protection defined by the claims.
Claims (10)
1. A preparation method of 2-bromo-5-aminopyridine is characterized in that bromine on 2, 6-dibromo-3-aminopyridine is removed through reduction reaction to obtain 2-bromo-5-aminopyridine.
2. The method for preparing 2-bromo-5-aminopyridine according to claim 1, wherein the reducing agent used in the reduction reaction is one or more selected from zinc metal, hydrogen gas, and ammonium formate.
3. The process for producing 2-bromo-5-aminopyridine according to claim 2, wherein the reducing agent used in the reduction reaction is zinc powder; the addition equivalent of zinc powder as a reducing agent is 1.0 to 1.5 times the equivalent of 2, 6-dibromo-3-aminopyridine as a substrate.
4. The method for preparing 2-bromo-5-aminopyridine according to claim 1, wherein the catalyst used in the reduction reaction is one or more selected from sodium hydroxide, potassium carbonate, palladium on charcoal, and platinum on charcoal.
5. The process for preparing 2-bromo-5-aminopyridine according to claim 1, wherein 2, 6-dibromo-3-aminopyridine is debrominated with a reducing agent in the presence of a first solvent and a catalyst to obtain the product 2-bromo-5-aminopyridine.
6. The process for preparing 2-bromo-5-aminopyridine according to claim 5, wherein the first solvent is one or more selected from the group consisting of water, acetonitrile, ethanol, and tetrahydrofuran; the reaction temperature of the reduction reaction is 20-100 ℃.
7. The method for preparing 2-bromo-5-aminopyridine according to claim 1, wherein 2, 6-dibromo-3-aminopyridine is synthesized by reacting pyridine compound with brominating reagent; the brominating reagent is selected from one or more of sodium bromide and sodium bromate; the pyridine compound is selected from one or more of 3-aminopyridine, 2-bromo-5-aminopyridine and 2-bromo-3-aminopyridine.
8. The process for producing 2-bromo-5-aminopyridine according to claim 7, wherein the reaction temperature for synthesizing 2, 6-dibromo-3-aminopyridine is 0 to 10 ℃; adding concentrated sulfuric acid into the mixed solution of the pyridine compound and the brominating reagent at the synthetic reaction temperature; the adding equivalent of the concentrated sulfuric acid is 1.0-2.0 times of the equivalent of the brominating reagent; the brominating reagent is sodium bromide and sodium bromate; the solvent of the mixed solution is water.
9. The process for preparing 2-bromo-5-aminopyridine according to claim 7, wherein the pyridine compound is partially or wholly derived from a debrominated by-product obtained by the reduction reaction.
10. Use of 2-bromo-5-aminopyridine synthesized according to the method of any one of claims 1 to 9 in pesticides, pharmaceuticals and liquid crystal materials.
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