CN115490646A - Preparation method of 3-nitro-1,2,4-triazole - Google Patents
Preparation method of 3-nitro-1,2,4-triazole Download PDFInfo
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- CN115490646A CN115490646A CN202211234835.4A CN202211234835A CN115490646A CN 115490646 A CN115490646 A CN 115490646A CN 202211234835 A CN202211234835 A CN 202211234835A CN 115490646 A CN115490646 A CN 115490646A
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- KUEFXPHXHHANKS-UHFFFAOYSA-N 5-nitro-1h-1,2,4-triazole Chemical compound [O-][N+](=O)C1=NC=NN1 KUEFXPHXHHANKS-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims abstract description 76
- 235000010288 sodium nitrite Nutrition 0.000 claims abstract description 38
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims abstract description 13
- KLZVAFKLKTUMIF-UHFFFAOYSA-N 3-diazo-1,2,4-triazole Chemical class [N-]=[N+]=C1N=CN=N1 KLZVAFKLKTUMIF-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 238000000297 Sandmeyer reaction Methods 0.000 claims abstract description 7
- 238000006193 diazotization reaction Methods 0.000 claims abstract description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- -1 3-diazo-1,2,4-triazole chloride salt Chemical compound 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims description 15
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical group [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 claims description 15
- 229940112669 cuprous oxide Drugs 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 14
- 239000012065 filter cake Substances 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 9
- 239000012295 chemical reaction liquid Substances 0.000 claims description 8
- 239000000047 product Substances 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 239000012943 hotmelt Substances 0.000 claims description 5
- 229910017604 nitric acid Inorganic materials 0.000 claims description 5
- 238000000967 suction filtration Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 239000002994 raw material Substances 0.000 abstract description 6
- 239000002699 waste material Substances 0.000 abstract description 5
- 238000005580 one pot reaction Methods 0.000 abstract description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- 239000012954 diazonium Substances 0.000 description 5
- 150000001989 diazonium salts Chemical class 0.000 description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- WIVXEZIMDUGYRW-UHFFFAOYSA-L copper(i) sulfate Chemical compound [Cu+].[Cu+].[O-]S([O-])(=O)=O WIVXEZIMDUGYRW-UHFFFAOYSA-L 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- 238000012565 NMR experiment Methods 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 229940045803 cuprous chloride Drugs 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000003034 chemosensitisation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000000637 radiosensitizating effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- URMVZUQDPPDABD-UHFFFAOYSA-N thieno[2,3-f][1]benzothiole Chemical compound C1=C2SC=CC2=CC2=C1C=CS2 URMVZUQDPPDABD-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
Abstract
The invention provides a preparation method of 3-nitro-1,2,4-triazole, which comprises the following steps: step S1, in the presence of inorganic acid, carrying out diazotization reaction on sodium nitrite and 3-amino-1,2,4-triazole to generate 3-diazo-1,2,4-triazole salt; and S2, in the presence of cuprous salt, carrying out a Sandmeyer reaction on the 3-diazo-1,2,4-triazole salt and sodium nitrite to generate 3-nitro-1,2,4-triazole. According to the preparation method provided by the embodiment of the invention, the used raw materials are good in safety, the one-pot preparation method and the single-pot efficiency are high, the three wastes are less, and the preparation method is environment-friendly.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a preparation method of 3-nitro-1,2,4-triazole.
Background
3-nitro-1,2,4-triazole is a coupling reagent and is commonly used in the fields of organic synthesis and biomedicine. For example, 3-nitro-1,2,4-triazole is one of basic raw material medicines for preparing N- (2-methoxyethyl) -2- (3-nitro-1,2,4, -triazole-1-) acetamide, and the acetamide injection is a novel tumor radiotherapy sensitizer, can increase the sensitivity of hypoxic cells in tumors to radiation, has various activities of radiosensitization, chemosensitization, metastasis inhibition, immunoregulation and the like, and has low toxicity and small irritation to a nervous system. In addition, 3-nitro-1,2,4-triazole can also be used as a soluble novel alternating conjugated copolymer raw material of thiophene, fluorene, benzo [1,2-b:4,5-b' ] dithiophene and thiophene derivatives containing 3-nitro-1,2,4-triazole side chains, and a structural unit of the copolymer has certain influence on the thermal property, the photophysical property, the electrochemical property and the photovoltaic property of the polymer.
At present, the preparation method of 3-nitro-1,2,4-triazole comprises the following steps:
1) Sodium tungstate catalysis and hydrogen peroxide oxidation. However, in the method, hydrogen peroxide is already decomposed in the process of dropping hydrogen peroxide at room temperature, so 5 molar ratios of hydrogen peroxide are needed to completely react, and the reaction time is longer and reaches more than 12 hours. The method has the problems of large quantity, low single kettle efficiency, large quantity of reducing agents needed for quenching redundant hydrogen peroxide, more generated waste water and the like.
2) Concentrated nitric acid and sodium nitrite oxidation method. However, in this method, a large amount of solid is generated during the dropwise addition of concentrated nitric acid, and it is necessary to add about 20 times as much water to stir uniformly, and the yield is low and the amount of waste acid water is large.
3) Other peroxide oxidation processes. However, these processes require excessive peroxide and are potentially hazardous to handle.
Disclosure of Invention
In view of the above, the invention aims to provide a preparation method of 3-nitro-1,2,4-triazole, which has the advantages of good raw material safety, one-pot preparation, high single-pot efficiency, less three wastes and environmental friendliness.
In order to solve the technical problems, the invention adopts the following technical scheme:
the preparation method of the 3-nitro-1,2,4-triazole according to the embodiment of the invention comprises the following steps:
step S1, in the presence of inorganic acid, carrying out diazotization reaction on sodium nitrite and 3-amino-1,2,4-triazole to generate 3-diazo-1,2,4-triazole salt;
and S2, in the presence of cuprous salt, enabling the 3-diazo-1,2,4-triazole salt to have a sandmeyer reaction with sodium nitrite to generate 3-nitro-1,2,4-triazole.
Further, in the step S1, the inorganic acid is one or more selected from hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid and tetrafluoroboric acid.
Still further, the step S1 includes:
3-amino-1,2,4-triazole is added into 6mol/L hydrochloric acid in batches, and then sodium nitrite is added in batches to generate 3-diazo-1,2,4-triazole chloride salt.
Furthermore, in the step S1, the molar ratio of 3-amino-1,2,4-triazole to hydrochloric acid and sodium nitrite is 1: (2.0-2.5): (1.0-1.3).
Furthermore, the temperature of adding the sodium nitrite in batches is 0-10 ℃, and the reaction time is 10-30 minutes.
Further, in the step S2, the cuprous salt is cuprous oxide.
Further, the step S2 includes:
cuprous oxide is added into 3-diazo-1,2,4-triazole chloride reaction liquid, and sodium nitrite water solution is dripped to generate 3-nitro-1,2,4-triazole.
Furthermore, the molar ratio of the 3-diazo-1,2,4-triazole chloride salt to the cuprous oxide and the sodium nitrite is 1 (1.5-3.0) to 1.5-3.0.
Furthermore, the temperature of the dropwise adding sodium nitrite aqueous solution is between 60 and 70 ℃, and the reaction time is between 1 and 3 hours.
Further, the method further comprises:
and S3, after the reaction is finished, cooling the reaction liquid to 5-10 ℃, performing suction filtration, performing hot-melt extraction on the primary filter cake with methanol at 50 ℃, then concentrating and filtering, collecting the secondary filter cake, and drying to obtain a pure product of 3-nitro-1,2,4-triazole.
The technical scheme of the invention at least has one of the following beneficial effects:
the preparation method provided by the embodiment of the invention has the advantages of good raw material safety, one-pot preparation, high single-pot efficiency, less three wastes and environmental friendliness.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the embodiments described are only a few embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the invention, are within the scope of the invention.
The production method according to the embodiment of the present invention is first specifically described below.
The preparation method of the 3-nitro-1,2,4-triazole according to the embodiment of the invention comprises the following steps:
step S1, in the presence of inorganic acid, carrying out diazotization reaction on sodium nitrite and 3-amino-1,2,4-triazole to generate 3-diazo-1,2,4-triazole salt.
That is, according to the method of the invention, sodium nitrite and 3-amino-1,2,4-triazole are selected as raw materials, and are subjected to diazotization reaction to obtain 3-diazo-1,2,4-triazole salt serving as an intermediate.
Generally, the diazotisation agent is generated temporarily from sodium nitrite with the action of a mineral acid medium. As the inorganic acid, in addition to hydrochloric acid, inorganic acids such as sulfuric acid, nitric acid, hydrobromic acid, tetrafluoroboric acid, and the like, or mixtures thereof can be used. Wherein, considering that the corrosivity of hydrochloric acid is relatively weaker than that of other acids and the reaction is faster, the other acids need to react for more than 5 hours compared with the reaction time of 10-30 minutes when the hydrochloric acid is used; further, hydrochloric acid is preferably used because the diazonium salt obtained by using hydrochloric acid as an inorganic acid medium has good purity and stability.
Specifically, the reaction formula is represented by the following formula (1):
of these, hydrochloric acid has a theoretical molar ratio of 2.0, but the reaction is preferably carried out in a strongly acidic medium, which on the one hand prevents the diazonium salt formed from decomposing and on the other hand avoids coupling side reactions between the diazonium salt formed and unreacted amine. Further, the theoretical molar ratio of sodium nitrite is 1.0, but if the amount of sodium nitrite is insufficient for this reaction, an amino-based diazo compound is easily generated. Based on the formula, the molar ratio of the 3-amino-1,2,4-triazole to the hydrochloric acid and the sodium nitrite can be set as 1: (2.0-2.5): (1.0-1.3). Preferably, the molar ratio is 1.0.
In some embodiments of the present application, the step S1 comprises: 3-amino-1,2,4-triazole is added into 6mol/L hydrochloric acid in batches, and then sodium nitrite is added in batches to generate 3-diazo-1,2,4-triazole chloride salt. The reaction concentration can be controlled moderately by diluting the hydrochloric acid molar concentration to 6 mol/L. In addition, sodium nitrite is added in batches, so that the reaction is controllable and is more sufficient.
Wherein the temperature of adding the sodium nitrite in batches is 0-10 ℃, and the reaction time is 10-30 minutes. The reaction conditions are easy to control, and the requirements on equipment are low.
In addition, according to the preparation method, the next reaction is directly carried out without purifying the intermediate after the first reaction step is finished, namely the method is a one-pot method or a single-pot method, so that the danger of the diazonium salt generated in the treatment process can be avoided.
And S2, in the presence of cuprous salt, carrying out a Sandmeyer reaction on the 3-diazo-1,2,4-triazole salt and sodium nitrite to generate 3-nitro-1,2,4-triazole.
That is, after the intermediate 3-diazo-1,2,4-triazole chloride is obtained, the intermediate and sodium nitrite are further subjected to a sandmeyer reaction under the action of cuprous salt to generate a final product 3-nitro-1,2,4-triazole.
Among them, as the cuprous salt used in sandmeyer reaction, cuprous sulfate, cuprous chloride, cuprous bromide, etc. can be selected, for example. Among them, the inventors have found through repeated studies that cuprous oxide has higher stability than other monovalent copper such as cuprous sulfate, and the use of excess sodium sulfite and copper sulfate to prepare cuprous sulfate can be avoided, making the reaction system more complicated. In addition, the target nitro compound can be directly produced by cuprous oxide, and if the product obtained by sandmeyer reaction using cuprous chloride or cuprous bromide inevitably contains chloride or bromide, further displacement reaction is required, which makes the reaction system complicated and the yield low. In view of the above, the cuprous salt is preferably cuprous oxide.
Specifically, the reaction formula is represented by the following formula (2):
considering that the reaction speed is slow, the cuprous oxide is slightly oxidized in storage, and in order to accelerate the reaction process and reduce the decomposition of the diazonium salt at a high temperature, the molar ratio of the cuprous oxide and the sodium nitrite which are reaction substrates can be properly increased, for example, the molar ratio of the 3-diazo-1,2,4-triazole chloride salt to the cuprous oxide and the sodium nitrite can be set to 1 (1.5-3.0) to (1.5-3.0). Preferably, the molar ratio is 1:2.0:2.0, in which case the reaction time can be shortened to 1-3 hours.
Further, the step S2 includes: cuprous oxide is added into 3-diazo-1,2,4-triazole chloride reaction liquid, and sodium nitrite water solution is dripped to generate 3-nitro-1,2,4-triazole.
Wherein the temperature of dropwise adding the sodium nitrite aqueous solution is 60-70 ℃, and the reaction time is 1-3 hours.
Further, the preparation method further comprises the following steps:
and S3, after the reaction is finished, cooling the reaction liquid to 5-10 ℃, carrying out suction filtration, carrying out hot-melt extraction on a primary filter cake by using methanol at 50 ℃, concentrating and filtering, collecting a secondary filter cake, and drying to obtain a pure product of 3-nitro-1,2,4-triazole.
Therefore, the preparation method has the advantages of simple purification of the final product, less three wastes and contribution to reducing the environmental protection pressure.
In order to make the technical solution of the present invention better understood by those skilled in the art, the present invention is further described in detail with reference to the following examples.
Example 1:
(1) Preparation of compound 3-diazo-1,2,4-triazole chloride salt
3-amino-1,2,4-triazole (20g, 0.238mol, 1.0eq) and 6M hydrochloric acid (87.3mL, 0.524mol, 2.2eq) are added into a 250mL reaction bottle, sodium nitrite (19.73g, 0.286mol, 1.2eq) is added in batches, and the temperature of ice water is controlled to be 0-10 ℃. After the reaction is finished, the solution is kept warm for 20 minutes to obtain 3-diazo-1,2,4-triazole chloride solution.
(2) Preparation of compound 3-nitro-1,2,4-triazole
Cuprous oxide (68.11g, 0.476mol and 2.0eq) is added into the 3-diazo-1,2,4-triazole chloride solution, the temperature is raised to 60-70 ℃, sodium nitrite (32.84g, 0.476mol and 2.0eq) solution is added dropwise into the solution, and the reaction is carried out for 2 hours after the addition. Cooling the reaction liquid to 5-10 ℃, then carrying out suction filtration, carrying out hot-melt extraction on a filter cake at 50 ℃ by using 60mL of methanol, concentrating at least a solvent when the methanol is left, filtering, collecting the filter cake, and drying to obtain 21.2g of a pure product, namely 3-nitro-1,2,4-triazole, wherein the liquid phase purity is 99.6 percent, and the yield is 78 percent.
The reactants were subjected to nmr experiments to confirm the product structure, and the data are as follows:
1H NMR (model: AVANCE III HD 400M, CDCl3, 400 MHz): delta =11.3 (s, 1H), 8.87 (s, 1H), and the detection result is consistent with the structure.
Example 2:
(1) Preparation of compound 3-diazo-1,2,4-triazole chloride salt
3-amino-1,2,4-triazole (45g, 0.535mol, 1.0eq) and 6M hydrochloric acid (196mL, 1.177mol, 2.2eq) are added into a 500mL reaction bottle, sodium nitrite (44.3g, 0.642mol, 1.2eq) is added in batches, and the temperature of ice water is controlled to be 0-10 ℃. After the reaction is finished, the solution is kept warm for 30 minutes to obtain 3-diazo-1,2,4-triazole chloride solution.
(2) Preparation of compound 3-nitro-1,2,4-triazole
Cuprous oxide (153.1g, 1.07mol, 2.0eq) is added into the 3-diazo-1,2,4-triazole chloride salt solution, the temperature is raised to 60-70 ℃, sodium nitrite (73.86g, 1.07mol, 2.0eq)/water (73.86 g) solution is added dropwise, and the heat preservation reaction is finished for 2.5 hours. Cooling the reaction liquid to 5-10 ℃, then carrying out suction filtration, carrying out hot-melt extraction on a filter cake at 50 ℃ by using 100mL of methanol, concentrating at least a solvent by using the methanol, filtering when the solvent is left, collecting the filter cake, and drying to obtain 46.9g of pure product 3-nitro-1,2,4-triazole, wherein the liquid phase purity is 99.5%, and the yield is 76.8%.
The reactants were subjected to nmr experiments to confirm the product structure, and the data are as follows:
1H NMR (model: AVANCE III HD 400M, CDCl3, 400 MHz): delta =12.1 (s, 1H), 8.86 (s, 1H), and the detection result is consistent with the structure.
While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (10)
1. A preparation method of 3-nitro-1,2,4-triazole is characterized by comprising the following steps:
step S1, in the presence of inorganic acid, carrying out diazotization reaction on sodium nitrite and 3-amino-1,2,4-triazole to generate 3-diazo-1,2,4-triazole salt;
and S2, in the presence of cuprous salt, carrying out a Sandmeyer reaction on the 3-diazo-1,2,4-triazole salt and sodium nitrite to generate 3-nitro-1,2,4-triazole.
2. The production method according to claim 1, wherein in the step S1, the inorganic acid is one or more selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, and tetrafluoroboric acid.
3. The method according to claim 2, wherein the step S1 includes:
3-amino-1,2,4-triazole is added into 6mol/L hydrochloric acid in batches, and then sodium nitrite is added in batches to generate 3-diazo-1,2,4-triazole chloride salt.
4. The production method according to claim 3, wherein in the step S1,
the molar ratio of 3-amino-1,2,4-triazole to hydrochloric acid and sodium nitrite is 1: (2.0-2.5): (1.0-1.3).
5. The method according to claim 4, wherein the temperature of the step of adding the sodium nitrite is 0 to 10 ℃ and the reaction time is 10 to 30 minutes.
6. The method according to claim 1, wherein the cuprous salt is cuprous oxide in the step S2.
7. The method according to claim 6, wherein the step S2 includes:
cuprous oxide is added into 3-diazo-1,2,4-triazole chloride reaction liquid, and sodium nitrite water solution is dripped to generate 3-nitro-1,2,4-triazole.
8. The preparation method of claim 7, wherein the molar ratio of the 3-diazo-1,2,4-triazole chloride salt to the cuprous oxide and the sodium nitrite is 1 (1.5-3.0) to (1.5-3.0).
9. The production method according to claim 7, wherein the temperature at which the aqueous solution of sodium nitrite is added dropwise is 60 to 70 ℃ and the reaction time is 1 to 3 hours.
10. The method of claim 7, further comprising:
and S3, after the reaction is finished, cooling the reaction liquid to 5-10 ℃, performing suction filtration, performing hot-melt extraction on the primary filter cake with methanol at 50 ℃, then concentrating and filtering, collecting the secondary filter cake, and drying to obtain a pure product of 3-nitro-1,2,4-triazole.
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