CN111892554B - Preparation method of 2,2' -biazonitrogen-bis (3-alkylbenzothiazoline-6-sulfonic acid) salt - Google Patents
Preparation method of 2,2' -biazonitrogen-bis (3-alkylbenzothiazoline-6-sulfonic acid) salt Download PDFInfo
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Abstract
The invention discloses a preparation method of 2,2' -biazonitrogen-bis (3-alkylbenzothiazoline-6-sulfonic acid) salt, which is characterized in that raw materials used in the preparation method are easy to obtain and low in price, and the production cost can be greatly reduced under the condition of ensuring high reaction yield, so that the large-scale production is facilitated.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of 2,2' -dinitro-bis (3-alkyl benzothiazoline-6-sulfonic acid) salt.
Background
2,2 '-biazobis (3-alkylbenzothiazoline-6-sulfonic acid) salts, in particular 2,2' -biazobis (3-ethylbenzothiazoline-6-sulfonic acid) diamine salt (ABTS), can be used in biochemical studies, e.g. spectroscopic reagents for free chlorine, chromogenic substrates for enzyme linked immunosorbent assays, substrates for peroxidases, for ELISA experiments. At present, few reports on the literature about synthesizing 2,2' -diaza-bis (3-ethylbenzthiazoline-6-sulfonic acid) diamine salt (ABTS) exist, the ABTS is expensive, and the search for a new optimized synthesis method of ABTS is of great significance. In the prior art, chinese patent 1 (application No. CN201811052610.0) discloses a method for synthesizing 2,2' -hydrazine-bis (3-ethylbenzothiazoline-6-sulfonic acid) diamine salt, which aims to solve the technical problems of expensive ABTS price and limited synthetic route, but in actual trial production, the preparation cost of the synthetic method is still high; in particular, the raw material 2-hydroxybenzothiazole used in the synthesis method is scarce in the market, so that the raw material is difficult to purchase and expensive, and the ABTS cost is high, so that the market demand cannot be met.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to: provides a preparation method of 2,2' -biazonitrogen-bis (3-alkylbenzothiazoline-6-sulfonic acid) salt, which is favorable for greatly reducing the cost, enlarging the production and having high reaction yield.
The purpose of the invention is realized by adopting the following technical scheme:
a preparation method of 2,2' -dinitrogen-bi (3-alkyl benzothiazole line-6-sulfonic acid) salt, which comprises five steps of reaction,
whereinY is at least one of halogen, phenol (OH), thiophenol (SH) and hydrogen atom; r is C which is saturated or unsaturated, linear or branched, containing hetero atoms or not containing hetero atoms 1 -C 30 One of the hydrocarbon groups;
the reaction comprises the specific steps of reacting,
step (1): reacting the compound 1 with an alkylating reagent to obtain a compound 2;
step (2): reacting the compound 2 with at least one of a sulfur-containing reagent and a halogenating reagent to obtain a compound 3;
and (3): reacting the compound 3 with a nitrogen-containing reagent to obtain a compound 4;
and (4): reacting the compound 4 with a sulfonation reagent to obtain a compound 5;
and (5): reacting compound 5 with an M-containing reagent to provide compound 6, wherein the M-containing reagent comprises: at least one of a base containing M, a salt containing M, an oxide containing M and a simple substance containing M; m is metal element, inorganic ammonium salt, organic ammonium salt, phosphorus salt,
At least one of a salt and an onium salt.
As a further example, the molar ratio of compound 5 to M-containing reagent is 1: 0.1-10.
As a further embodiment, the method also comprises a step (6), wherein in the step (6), the crude product is recrystallized by using a drying sealing device under a drying condition or a solvent under a drying gas purging condition, and the crude product is crystallized, filtered and dried under a low temperature condition to obtain a refined product.
As a further example, the solvent in step (6) is one or more of methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, dimethyl sulfoxide, water.
As a further embodiment, the alkylating agent includes at least one of dialkyl sulfate, alkyl sulfate, halide of alkyl, alcohol corresponding to alkyl, thiol corresponding to alkyl;
the molar ratio of compound 1 to alkylating agent is 1: 0.1-10.
As a further example, the sulfur-containing reagent is carbon disulfide,
Or the corresponding salts,
Or the corresponding salt,
Or at least one of corresponding salt, thiocyanate, sulfide and sulfur powder;
the halogenating agent comprises at least one of halogen simple substance, hydrogen halide and halogen acid;
the molar ratio of the compound 2 to the sulfur-containing reagent is 1: 0.1 to 10; the molar ratio of the compound 2 to the halogenating agent is 1: 0.1-10.
As a further embodiment, the nitrogen-containing reagent is at least one of hydrazine and hydrazine hydrate;
the molar ratio of the compound 3 to the nitrogen-containing reagent is 1: 0.1-10.
As a further embodiment, the sulfonating agent is at least one of sulfuric acid, oleum, sulfur trioxide;
the molar ratio of the compound 4 to the sulfonating agent is 1: 0.1-10.
As a further example, the reactants in steps (1) to (5) are reacted in a solvent, and the solvent in steps (1) to (5) is at least one of methanol, ethanol, acetone, tetrahydrofuran, dichloroethane, dichloromethane, ethyl acetate, ethyl formate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, dimethyl sulfoxide, and water.
As a further example, the reaction temperature in the steps (1) to (5) is-20 to 200 ℃, the reaction pressure is 0 to 1MPa (gauge pressure), and the reaction time is 0.1 to 72 hours.
Compared with the prior art, the invention has the beneficial effects that:
the invention discloses a preparation method of 2,2' -biazonitrogen-bis (3-alkylbenzothiazoline-6-sulfonic acid) salt, which is easy to obtain raw materials used in the preparation method, has low price, and can greatly reduce the production cost under the condition of ensuring high reaction yield, thereby being beneficial to large-scale production. Meanwhile, the preparation method is different from the prior novel preparation process, and the novel preparation process is helpful for academic research, industrial research and practice of ABTS in the field, thereby promoting the development of related technologies and related industrial economy in the field.
Detailed Description
The present invention is further described below with reference to specific embodiments, and it should be noted that, without conflict, any combination between the embodiments or technical features described below may form a new embodiment.
The pressure values mentioned in this patent application refer to gauge pressure unless otherwise specified.
The yield, as a percentage ratio of actual product mass to theoretical product mass, and theoretical product mass, were calculated as the raw materials in the reaction equation were not in excess.
The test method comprises the following steps: nuclear magnetic analysis was performed using an AVANCE 400 mega nuclear magnetic resonance spectrometer from Bruker (Bruker).
Example 1:
this example provides a process for the preparation and purification of 2,2' -biazobis (3-ethylbenzothiazoline-6-sulfonic acid) diamine salt (ABTS):
step 1:
compound 2 is produced by reacting 1 mole of compound 1 with diethyl sulfate in a reactor. Wherein the molar ratio of the compound 1 to the diethyl sulfate is 1: 1; the solvent is tetrahydrofuran, the reaction temperature is 20 ℃, the reaction pressure is normal pressure, the reaction time is 8 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 2 in 65% yield.
Step 2:
in the reactor, 1 mole of compound 2 is reacted with carbon disulfide to produce compound 3. Wherein the molar ratio of the compound 2 to the carbon disulfide is 1: 1; the solvent is tetrahydrofuran, the reaction temperature is 60 ℃, the reaction pressure is 0.5MPa, the reaction time is 8 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 3 in 70% yield.
And step 3:
in the reactor, 1 mol of compound 3 is reacted with hydrazine hydrate to prepare compound 4. Wherein the molar ratio of the compound 3 to the hydrazine hydrate is 1: 1; the solvent is tetrahydrofuran, the reaction temperature is 60 ℃, the reaction pressure is normal pressure, the reaction time is 8 hours, and the reaction is finished.
The solvent was removed by evaporation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by evaporation to give compound 4 in 75% yield.
And 4, step 4:
in the reactor, 1 mole of compound 4 was reacted with oleum to prepare compound 4. Wherein the molar ratio of the compound 3 to the oleum is 1: 2; the solvent is dichloroethane, the reaction temperature is 0 ℃, the reaction pressure is normal pressure, the reaction time is 8 hours, and the reaction is finished.
Slowly pouring the reaction solution onto crushed ice, continuously stirring, performing suction filtration to obtain a dark blue-green solid, washing the solid twice with a small amount of water, washing off sulfuric acid contained in the solid, and performing suction filtration to dryness to obtain a compound 4 with the yield of 75%.
And 5:
reacting 1 mol of compound 5 with ammonia water in a reactor to prepare a compound 6; wherein the molar ratio of the compound 5 to ammonia water is 1: 2; the solvent is methanol, the reaction temperature is 0 ℃, the reaction pressure is normal pressure, the reaction time is 8 hours, and the reaction is finished.
And (3) carrying out suction filtration to obtain a crude product, and removing part of the solvent from the filtrate through rotary evaporation to obtain a part of the crude product, so as to finally obtain a compound 6 with the yield of 70%.
Step 6:
in the reactor, 1 mole of the crude compound 6 was purified: and (2) recrystallizing the crude product by using a solvent (methanol) under a drying condition and a drying sealed device or under a dry gas purging condition, crystallizing at a low temperature, then removing insoluble substances by suction filtration, removing the methanol from the filtrate by rotary evaporation, and drying to obtain a refined product with the purification yield of 80%.
And (3) testing results:
the nmr characterization data is as follows: 1 H NMR(400MHz,DMSO-d 6 ):δ1.27(6H),4.07(4H),7.10(10H),7.49-7.52(2H),7.71(2H)；
the above nuclear magnetic results are consistent with those of commercially available ABTS standards.
Purity of the ABTS top-quality was 99.5% as measured by HPLC analysis.
Example 2:
this example provides a process for the preparation and purification of 2,2' -biazobis (3-ethylbenzothiazoline-6-sulfonic acid) diamine salt (ABTS):
step 1:
compound 2 is produced by reacting 1 mole of compound 1 with bromoethane in a reactor. Wherein the molar ratio of the compound 1 to bromoethane is 1: 1; the solvent is tetrahydrofuran, the reaction temperature is 20 ℃, the reaction pressure is normal pressure, the reaction time is 8 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 2 in 60% yield.
Step 2:
in the reactor, 1 mol of compound 2, a halogenating agent (bromine) and carbon disulfide are reacted to prepare compound 3. Wherein the molar ratio of the compound 2 to the halogenating agent is 1:1, and the molar ratio of the compound 2 to the carbon disulfide is 1: 1; the solvent is tetrahydrofuran, the reaction temperature is 60 ℃, the reaction pressure is 0.5MPa, the reaction time is 8 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 3 in 65% yield.
And step 3:
in the reactor, 1 mol of compound 3 is reacted with hydrazine hydrate to prepare compound 4. Wherein the molar ratio of the compound 3 to the hydrazine hydrate is 1: 1; the solvent is acetonitrile, the reaction temperature is 70 ℃, the reaction pressure is normal pressure, the reaction time is 10 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 4 in 72% yield.
And 4, step 4:
in the reactor, 1 mole of compound 4 was reacted with oleum to prepare compound 4. Wherein the molar ratio of the compound 3 to the oleum is 1: 2; the solvent is ethyl acetate, the reaction temperature is 10 ℃, the reaction pressure is normal pressure, the reaction time is 9 hours, and the reaction is finished.
Slowly pouring the reaction solution onto crushed ice, continuously stirring, performing suction filtration to obtain a dark blue-green solid, washing the solid twice with a small amount of water, washing off sulfuric acid contained in the solid, and performing suction filtration to dryness to obtain a compound 4 with the yield of 75%.
And 5:
reacting 1 mol of compound 5 with ammonia gas in a reactor to prepare a compound 6; wherein the molar ratio of the compound 5 to ammonia gas is 1: 10; the solvent is ethanol, the reaction temperature is 5 ℃, the reaction pressure is 1MPa, the reaction time is 12 hours, and the reaction is finished.
And (3) carrying out suction filtration to obtain a crude product, and removing part of the solvent from the filtrate through rotary evaporation to obtain a part of the crude product, so as to finally obtain a compound 6 with the yield of 73%.
Step 6:
in the reactor, 1 mole of the crude compound 6 was purified: and (2) recrystallizing the crude product by using a solvent (ethanol) under a drying condition and a drying sealed device or under a dry gas purging condition, crystallizing at a low temperature, then removing insoluble substances by suction filtration, removing the methanol from the filtrate by rotary evaporation, and drying to obtain a refined product with the purification yield of 81%.
And (3) testing results:
the nmr characterization data is as follows: 1 H NMR(400MHz,DMSO-d 6 ):δ1.27(6H),4.07(4H),7.10(10H),7.49-7.52(2H),7.71(2H)；
the above nuclear magnetic results are consistent with those of commercially available ABTS standards.
Purity of the ABTS top-quality was 99.6% as measured by HPLC analysis.
Example 3:
this example provides a process for the preparation and purification of 2,2' -diaza-bis (3-ethylbenzothiazoline-6-sulfonic acid) diamine salt (ABTS):
step 1:
compound 2 is produced by reacting 1 mole of compound 1 with bromoethane in a reactor. Wherein the molar ratio of the compound 1 to bromoethane is 1: 1; the solvent is tetrahydrofuran, the reaction temperature is 20 ℃, the reaction pressure is normal pressure, the reaction time is 8 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 2 in 62% yield.
Step 2:
in the reactor, 1 mol of compound 2, a halogenating agent (bromine) and carbon disulfide are reacted to prepare compound 3. Wherein the molar ratio of the compound 2 to the halogenating agent is 1:1, and the molar ratio of the compound 2 to the carbon disulfide is 1: 1; the solvent is tetrahydrofuran, the reaction temperature is 60 ℃, the reaction pressure is 0.5MPa, the reaction time is 8 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 3 in 60% yield.
And step 3:
in the reactor, 1 mol of compound 3 is reacted with hydrazine hydrate to prepare compound 4. Wherein the molar ratio of the compound 3 to the hydrazine hydrate is 1: 1; the solvent is ethyl formate, the reaction temperature is 65 ℃, the reaction pressure is normal pressure, the reaction time is 7 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 4 in 71% yield.
And 4, step 4:
in the reactor, 1 mole of compound 4 was reacted with oleum to prepare compound 4. Wherein the molar ratio of the compound 3 to the oleum is 1: 2; the solvent is dichloromethane, the reaction temperature is-5 ℃, the reaction pressure is normal pressure, the reaction time is 9 hours, and the reaction is finished.
Slowly pouring the reaction solution on crushed ice, continuously stirring, performing suction filtration to obtain a dark blue-green solid, washing the solid twice with a small amount of water, washing off sulfuric acid contained in the solid, and performing suction filtration to dryness to obtain a compound 4 with the yield of 70%.
And 5:
reacting 1 mol of compound 5 with ammonia water in a reactor to prepare a compound 6; wherein the molar ratio of the compound 5 to ammonia water is 1: 2; the solvent is diethyl carbonate, the reaction temperature is 5 ℃, the reaction pressure is normal pressure, the reaction time is 11 hours, and the reaction is finished.
And (3) carrying out suction filtration to obtain a crude product, and removing part of the solvent from the filtrate through rotary evaporation to obtain a part of the crude product, so as to finally obtain a compound 6 with the yield of 69%.
Step 6:
in the reactor, 1 mole of the crude compound 6 was purified: and (2) recrystallizing the crude product by using a solvent (diethyl carbonate) under a drying condition and a drying sealed device or under a dry gas purging condition, crystallizing at a low temperature, then filtering and removing insoluble substances, removing methanol from the filtrate by rotary evaporation, and drying to obtain a refined product with the purification yield of 79%.
And (3) testing results:
the nmr characterization data is as follows: 1 H NMR(400MHz,DMSO-d 6 ):δ1.27(6H),4.07(4H),7.10(10H),7.49-7.52(2H),7.71(2H)；
the above nuclear magnetic results are consistent with those of commercially available ABTS standards.
Purity of the ABTS top-quality was 99.4% as measured by HPLC analysis.
Example 4:
this example provides a process for the preparation and purification of 2,2' -biazobis (3-ethylbenzothiazoline-6-sulfonic acid) diamine salt (ABTS):
step 1:
compound 2 is produced by reacting 1 mole of compound 1 with bromoethane in a reactor. Wherein the molar ratio of the compound 1 to bromoethane is 1: 1; the solvent is tetrahydrofuran, the reaction temperature is 20 ℃, the reaction pressure is normal pressure, the reaction time is 8 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 2 in 80% yield.
Step 2:
in the reactor, 1 mol of compound 2, a halogenating agent (bromine) and carbon disulfide are reacted to prepare compound 3. Wherein the molar ratio of the compound 2 to the halogenating agent is 1:1, and the molar ratio of the compound 2 to the carbon disulfide is 1: 1; the solvent is tetrahydrofuran, the reaction temperature is 60 ℃, the reaction pressure is 0.5MPa, the reaction time is 8 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 3 in 60% yield.
And step 3:
in the reactor, 1 mol of compound 3 is reacted with hydrazine hydrate to prepare compound 4. Wherein the molar ratio of the compound 3 to the hydrazine hydrate is 1: 1; the solvent is diethyl carbonate, the reaction temperature is 55 ℃, the reaction pressure is normal pressure, the reaction time is 6 hours, and the reaction is finished.
The solvent was removed by rotation, ethyl acetate was added, washed twice with water, dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotation to give compound 4 in 72% yield.
And 4, step 4:
in the reactor, 1 mole of compound 4 was reacted with oleum to prepare compound 4. Wherein the molar ratio of the compound 3 to the oleum is 1: 2; the solvent is dichloroethane, the reaction temperature is-10 ℃, the reaction pressure is normal pressure, the reaction time is 7 hours, and the reaction is finished.
Slowly pouring the reaction solution onto crushed ice, continuously stirring, performing suction filtration to obtain a dark blue-green solid, washing the solid twice with a small amount of water, washing off sulfuric acid contained in the solid, and performing suction filtration to dryness to obtain a compound 4 with a yield of 72%.
And 5:
reacting 1 mol of compound 5 with ammonia water in a reactor to prepare a compound 6; wherein the molar ratio of the compound 5 to ammonia water is 1: 2; the solvent is methanol, the reaction temperature is-20 ℃, the reaction pressure is normal pressure, the reaction time is 11 hours, and the reaction is finished.
And (3) carrying out suction filtration to obtain a crude product, and removing part of the solvent from the filtrate through rotary evaporation to obtain a part of the crude product, so as to finally obtain a compound 6 with the yield of 73%.
Step 6:
in the reactor, 1 mole of the crude compound 6 was purified: and (2) recrystallizing the crude product by using a solvent (acetonitrile) under a drying condition and a drying sealed device or under a dry gas purging condition, crystallizing at a low temperature, then removing insoluble substances by suction filtration, removing methanol from the filtrate by rotary evaporation, and drying to obtain a refined product with the purification yield of 80%.
And (3) testing results:
the nmr characterization data is as follows: 1 H NMR(400MHz,DMSO-d 6 ):δ1.27(6H),4.07(4H),7.10(10H),7.49-7.52(2H),7.71(2H)；
the above nuclear magnetic results are consistent with those of commercially available ABTS standards.
Purity of the ABTS top-grade was 99.5% by HPLC analysis.
The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.
Claims (10)
1. A preparation method of 2,2' -biazonitrogen-bis (3-alkylbenzothiazoline-6-sulfonic acid) salt is characterized by comprising the following five steps of reaction:
wherein Y is at least one of halogen, phenol, thiophenol and hydrogen atom; r is C which is saturated or unsaturated, linear or branched, containing hetero atoms or not containing hetero atoms 1 -C 30 One of the hydrocarbon groups;
the reaction comprises the specific steps of reacting,
step (1): reacting the compound 1 with an alkylating reagent to obtain a compound 2;
step (2): reacting the compound 2 with at least one of a sulfur-containing reagent and a halogenating reagent to obtain a compound 3;
and (3): reacting the compound 3 with a nitrogen-containing reagent to obtain a compound 4; the nitrogen-containing reagent is at least one of hydrazine and hydrazine hydrate;
and (4): reacting the compound 4 with a sulfonation reagent to obtain a compound 5;
and (5): reacting compound 5 with an M-containing reagent to provide compound 6, wherein the M-containing reagent comprises: at least one of a base containing M, a salt containing M, an oxide containing M and a simple substance containing M; m is metal element, inorganic ammonium salt, organic ammonium salt, phosphorus salt,
At least one of a salt and an onium salt.
2. The method of claim 1, wherein: the molar ratio of the compound 5 to the M-containing reagent is 1: 0.1-10.
3. The method of claim 1, wherein: and (6) recrystallizing the crude product by using a drying sealing device under a drying condition or using a solvent under a drying gas blowing condition, crystallizing at a low temperature, filtering and drying to obtain a refined product, wherein the solvent is used for dissolving the crude product in the solvent, and the solvent is used for dissolving the crude product in the solvent.
4. The method of claim 3, wherein: the solvent in the step (6) is one or more of methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, dimethyl sulfoxide and water.
5. The method of claim 1, wherein: the alkylating agent comprises at least one of dialkyl sulfate, alkyl halide, alcohol corresponding to the alkyl and mercaptan corresponding to the alkyl;
the molar ratio of the compound 1 to the alkylating agent is 1: 0.1-10.
6. The method of claim 1, wherein: the sulfur-containing reagent is carbon disulfide,
Or the corresponding salts,
Or the corresponding salts,
Or at least one of corresponding salt, thiocyanate, sulfide and sulfur powder;
the halogenating agent comprises at least one of halogen simple substance, hydrogen halide and halogen acid;
the molar ratio of the compound 2 to the sulfur-containing reagent is 1: 0.1 to 10; the molar ratio of the compound 2 to the halogenating agent is 1: 0.1-10.
7. The method of claim 1, wherein: the molar ratio of the compound 3 to the nitrogen-containing reagent is 1: 0.1-10.
8. The method of claim 1, wherein: the sulfonation reagent is at least one of sulfuric acid, fuming sulfuric acid and sulfur trioxide;
the molar ratio of the compound 4 to the sulfonating agent is 1: 0.1-10.
9. The method of claim 1, wherein: reacting the reactants in the steps (1) to (5) in a solvent, wherein the solvent in the steps (1) to (5) is at least one of methanol, ethanol, acetone, tetrahydrofuran, dichloroethane, dichloromethane, ethyl acetate, ethyl formate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, dimethyl sulfoxide and water.
10. The method of claim 1, wherein: the reaction temperature of the step (1) to the step (5) is-20 to 200 ℃, the reaction pressure is 0 to 1MPa, and the reaction time is 0.1 to 72 hours.
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| CN112250634A (en) * | 2020-10-22 | 2021-01-22 | 苏州亚科科技股份有限公司 | Preparation method of 4-phenylimidazole |
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| CN103073522A (en) * | 2013-01-14 | 2013-05-01 | 江西师范大学 | Synthesis method of 2,2' -biazoyl-di (3-ethyl-benzothiazole-6-sulfonic acid) diammonium salt |
| CN109020918A (en) * | 2018-08-14 | 2018-12-18 | 南京艾普特生物医药有限公司 | The synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride and its hydrate |
| CN108752289A (en) * | 2018-09-10 | 2018-11-06 | 南京艾普特生物医药有限公司 | 2,2 '-hydrazines-bis-（3- ethyl benzo thiazole phenanthroline -6- sulfonic acid）The synthetic method of diamine salts |
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