CN114230470A - Synthetic method and application of stable isotope labeled benzidine - Google Patents

Synthetic method and application of stable isotope labeled benzidine Download PDF

Info

Publication number
CN114230470A
CN114230470A CN202111557533.6A CN202111557533A CN114230470A CN 114230470 A CN114230470 A CN 114230470A CN 202111557533 A CN202111557533 A CN 202111557533A CN 114230470 A CN114230470 A CN 114230470A
Authority
CN
China
Prior art keywords
labeled
stable isotope
benzidine
added
synthetic method
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202111557533.6A
Other languages
Chinese (zh)
Inventor
郑悦
石磊
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beijing Manhattan Biotechnology Co ltd
Original Assignee
Manhag Testing Technology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Manhag Testing Technology Co ltd filed Critical Manhag Testing Technology Co ltd
Priority to CN202111557533.6A priority Critical patent/CN114230470A/en
Publication of CN114230470A publication Critical patent/CN114230470A/en
Pending legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/68Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/68Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
    • C07C209/74Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

本发明公开了一种稳定同位素标记的联苯胺的合成方法及其应用,合成方法包括:将稳定同位素标记的苯胺与N‑溴代丁二酰亚胺置于有机溶剂中混合,加入催化剂后在室温下搅拌反应,反应后对混合物进行后处理得到4‑溴苯胺‑13C6H4;在氮气气氛保护下,将得到的4‑溴苯胺‑13C6H4加入到含有钯/碳催化剂、乙酸钾和双(频哪醇合)二硼的乙醇溶液中,加热搅拌,反应后冷却至室温,并对得到的反应物进行再处理,即得稳定同位素标记的联苯胺。本发明所提供的方法步骤简单且工艺可控,具有效率高和产率高的优势;本发明所制备得到的稳定同位素标记的4,4'‑联苯胺‑13C12H8的质量稳定,具有极大的开发利用价值。The invention discloses a method for synthesizing stable isotope-labeled benzidine and application thereof. The synthesis method comprises: placing stable isotope-labeled aniline and N-bromosuccinimide in an organic solvent and mixing, adding a catalyst and adding The reaction was stirred at room temperature, and after the reaction, the mixture was post-treated to obtain 4 -bromoaniline - 13C6H4 ; under nitrogen atmosphere protection, the obtained 4 -bromoaniline - 13C6H4 was added to a catalyst containing palladium/carbon , potassium acetate and bis(pinacol) diboron in ethanol solution, heat and stir, cool to room temperature after the reaction, and reprocess the obtained reactant to obtain stable isotope-labeled benzidine. The method provided by the invention has simple steps and controllable process, and has the advantages of high efficiency and high yield; the stable isotope-labeled 4,4'-benzidine- 13 C 12 H 8 prepared by the invention has stable quality, It has great development and utilization value.

Description

Synthetic method and application of stable isotope labeled benzidine
Technical Field
The invention relates to the technical field of isotope labeling, in particular to a synthetic method of stable isotope labeled benzidine and application thereof.
Background
Benzidine (trivial name), also known as 1, 1 '-biphenyl-4, 4' -diamine (systematic name), is an organic compound having the molecular formula (C)6H4NH2)2White or slightly reddish stable acicular crystal or powder, flammable, darkened when exposed to air and irradiated by light, and commercially available products are often brown or deep purple brown and are insoluble in cold waterSlightly soluble in hot water and ether, and easily soluble in acetic acid, dilute hydrochloric acid and boiling ethanol; as an aromatic amine, the chemical property is similar to that of aniline, diazotization reaction can be carried out with nitrous acid to generate diazonium salt, and the diazonium salt is coupled with aromatic amine or phenol to obtain various benzidine dyes. Benzidine was an important intermediate for dye synthesis, from which more than 300 dyes could be synthesized, but due to its strong toxicity, other less toxic starting materials have been used; benzidine and its salt are toxic and carcinogenic substances, and solid and vapor easily enter into body through skin, cause contact dermatitis, irritate mucous membrane, damage liver and kidney, and cause bladder cancer and pancreatic cancer; as long as the concentration of benzidine reaches 6.7ppb, there is a risk of carcinogenesis in humans.
Benzidine, because of its enormous carcinogenic risk, its use should be banned; to prevent and stop the continued use of benzidine in pigment production, a technique is needed that can detect it quickly, accurately, and very sensitively.
Stable Isotope Dilution Mass Spectrometry (IDMS) uses a stable Isotope labeled compound having the same molecular structure as a substance to be detected as an internal standard substance, and a high resolution liquid chromatography-Mass spectrometer (LC/MS) is used for detection, and the Mass spectrometer is used for measuring the ratio of ions with corresponding Mass numbers and comparing the ratio with a standard ratio to achieve the purpose of accurate quantification. The isotope internal standard can effectively eliminate the recovery rate difference of the sample in the chemical and physical pretreatment steps, thereby avoiding the deviation of the detection result caused by the loss of the sample treatment process.
This property of stable isotope internal standards, combined with the high sensitivity of LC/MS and the ability to process complex samples, makes the chromatography/isotope dilution mass spectrometry technique recognized as a baseline method for measuring trace and trace organics; the successful development of the stable isotope labeled benzidine provides a standard reagent for more accurate quantitative detection of the benzidine, thereby effectively providing residual detection service for the dye industry safety field in China.
The stable isotope labeled benzidine currently available on the market is benzidine-d 8 shown below.
Figure BDA0003419511670000021
In particular, deuterium of benzidine-d 8 is bonded to a conjugated bond of a benzene ring and is easily replaced by hydrogen in a solvent, so that the deuterium label is lost; the 8 deuterium atoms also easily cause Matrix effect (Matrix effect) of the internal standard, and may cause errors due to non-co-flow between the standard and the analyte during LC-MS analysis.
To overcome the defects of benzidine-d 8, the stable isotope labeled benzidine (4, 4' -benzidine-13C12H8) The synthesis method of (2) is already in need.
In view of this, the invention is particularly proposed.
Disclosure of Invention
In view of this, the invention provides a method for synthesizing stable isotope labeled benzidine and applications thereof.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a method for synthesizing stable isotope labeled benzidine, wherein the molecular structural formula of the stable isotope labeled benzidine is as follows:
Figure BDA0003419511670000031
the synthesis method comprises the following steps:
s1, placing aniline marked by stable isotope and N-bromosuccinimide into an organic solvent for mixing, adding a catalyst, stirring at room temperature for reaction, and carrying out post-treatment on the obtained mixture after the reaction is finished to obtain 4-bromoaniline-13C6H4
S2, under the protection of nitrogen atmosphere, the 4-bromoaniline obtained in the step S113C6H4Adding into ethanol solution containing palladium/carbon catalyst, potassium acetate and bis (pinacolato) diboron, heating and stirring, reacting, and coolingCooling to room temperature, and reprocessing the obtained reactant to obtain the benzidine labeled by the stable isotope.
In the above technical solution, in step S1, the catalyst is ammonium acetate.
In a preferred embodiment of the present invention, in step S1, the catalyst is added in a molar amount of 0.08 to 0.125 times that of the stable isotope-labeled aniline.
In the above technical scheme, in step S1, the stirring reaction time is 10-60 min.
In the above technical solution, in step S1, the molar weight of the N-bromosuccinimide added is 1.0 to 1.15 times that of the stable isotope-labeled aniline.
In the above technical solution, in step S1, the organic solvent is acetonitrile.
Further, in the above technical solution, in step S1, the post-processing includes:
concentrating the mixture obtained after the reaction is finished, then adding saturated sodium bicarbonate solution and extracting with ethyl acetate, separating the obtained extract and collecting an organic phase, drying and concentrating, and finally carrying out column chromatography purification on the residue to obtain 4-bromoaniline-13C6H4
Specifically, in the above technical solution, in step S1, the mixture obtained after the reaction is completed is concentrated to dryness, and then a saturated sodium bicarbonate solution is added.
Specifically, in the above technical solution, in step S1, the amount of the saturated sodium bicarbonate solution added is 20 to 50mL, corresponding to 10mmol of aniline.
In the above technical solution, in step S2, the molar amount of the palladium/carbon catalyst added in the ethanol solution is 4-bromoaniline-13C6H40.01-0.1 times of the total weight of the composition.
In the above technical scheme, in the step S2, the molar amount of the potassium acetate added in the ethanol solution is 4-bromoaniline-13C6H42.75-3.6 times of the total weight of the powder.
In the above technical solution, in step S2, the molar amount of the bis (pinacolato) diboron added into the ethanol solution is 4-bromoaniline-13C6H41.35-1.8 times of the total weight of the composition.
In the above technical solution, in step S2, the heating and stirring temperature and time are 55-72 ℃ and 7.5-9h, respectively.
Further, in the above technical solution, in step S2, the reprocessing includes:
filtering the obtained reactant, taking the filtrate, concentrating under reduced pressure, adding saturated sodium bicarbonate solution, extracting with dichloromethane, separating the obtained extract, collecting an organic phase, drying, concentrating, and finally performing column chromatography purification on the residue to obtain the benzidine labeled by the stable isotope.
The invention also provides the synthesis method for preparing the stable isotope labeled 4,4' -benzidine-13C12H8The use of (1).
Compared with the prior art, the invention has the following advantages:
(1) the preparation of stable isotope labeled 4,4' -benzidine-13C12H8The method has the advantages of simple steps, controllable process, high efficiency and high yield;
(2) the stable isotope labeled 4,4' -benzidine-13C12H8The quality of the standard is stable, the mass spectrum of the standard as an internal standard is definite, a Matrix effect (Matrix effect) cannot be caused in the LC-MS analysis process, and the phenomenon of non-cocurrent flow cannot occur with the analyte in the LC-MS analysis process, so that the analysis error is avoided, a standard reagent is provided for more accurately and quantitatively detecting the benzidine, and the residual detection service in the dye industry safety field of China is effectively provided; has great development and utilization value.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments.
It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
In the examples, the means used are conventional in the art unless otherwise specified.
The terms "comprises," "comprising," or any other variation thereof, as used herein, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.
In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
Unless otherwise specified, the raw materials used in the examples of the present invention are all commercially available products.
In order to facilitate a further understanding of the present invention, the technical solutions of the present invention will now be described in detail with reference to the preferred embodiments.
Example 1
The embodiment of the invention provides a method for synthesizing stable isotope labeled benzidine, which comprises the following steps:
s1, to a 250mL round bottom flask containing 50mL acetonitrile (AcCN), aniline (991mg, 10.0mmol) was added followed by NH4OAc (77.1mg, 1.0mmol), N-bromosuccinimide (NBS, 1.78g, 10.0mmol) was added, the mixture was stirred at room temperature for 10min, after completion of the reaction, the reaction mixture was concentrated to dryness by a rotary evaporator, 25ml of a saturated sodium bicarbonate solution was added, followed by extraction with ethyl acetate (25ml 3 times), the obtained extracts were separated and the organic phase was collected, combined and dried with anhydrous sodium sulfate (30 g) (room temperature, 1-2 hours), then concentrated to dryness by a rotary evaporator, and finally the residue was purified by column chromatography (silica gel, hexane-ethyl acetate, 10: 1) to obtain 1.53 g of light brown solid 4-bromoaniline-13C6H4
S2, under the protection of nitrogen, loadingA250 ml round bottom flask with 35ml of anhydrous ethanol was charged with 1.62g of 4-bromoaniline-13C6H4And 3.47g bis (pinacolato) diboron, then introducing nitrogen gas into the resulting solution for 5min, then successively adding palladium-carbon (10%, 96.8mg) and potassium acetate (2.68g), continuing to introduce nitrogen gas for 5min, then heating the mixture to 60 ℃, stirring for 8h, cooling the reactor to room temperature, filtering the reaction mixture, concentrating the filtrate under reduced pressure, adding 25ml of saturated sodium bicarbonate solution, extracting the residue with dichloromethane (25 ml. times.3), separating the obtained extracts and collecting the organic phases, combining, drying over magnesium sulfate and vacuum concentrating to dryness, and finally purifying the residue by column chromatography (silica gel, hexane-ethyl acetate, 10: 2) to obtain 1.55g of stable isotope labeled 4,4' -benzidine-13C12H8
Example 2
The embodiment of the invention provides a method for synthesizing stable isotope labeled benzidine, which comprises the following steps:
s1, to a 250mL round bottom flask containing 50mL acetonitrile (AcCN), aniline (991mg, 10.0mmol) was added followed by NH4OAc (77.1mg, 1.0mmol), N-bromosuccinimide (NBS, 1.87g, 10.5mmol) was added, the mixture was stirred at room temperature for 10min, after completion of the reaction, the reaction mixture was concentrated to dryness by a rotary evaporator, 25ml of a saturated sodium bicarbonate solution was added, followed by extraction with ethyl acetate (25ml 3 times), the obtained extracts were separated and the organic phase was collected, combined and dried with anhydrous sodium sulfate (30 g) (room temperature, 1-2 hours), then concentrated to dryness by a rotary evaporator, and finally the residue was purified by column chromatography (silica gel, hexane-ethyl acetate, 10: 1) to obtain 1.71 g of light brown solid 4-bromoaniline-13C6H4
S2, under the protection of nitrogen, adding 1.62g of 4-bromoaniline into a 250ml round-bottom flask containing 35ml of absolute ethyl alcohol13C6H4And 3.47g bis (pinacolato) diboron, then introducing nitrogen into the resulting solution for 5min, then adding palladium-carbon (10%, 484.0mg) followed by potassium acetate (2.68g), continuing with nitrogen for 5min, and then adding the mixture to a reactorThe mixture was heated to 60 ℃ and stirred for 8h, the reactor was cooled to room temperature, the reaction mixture was filtered, the filtrate was concentrated under reduced pressure, 25ml of saturated sodium bicarbonate solution was added, the residue was extracted with dichloromethane (25ml 3 times), the obtained extracts were separated and the organic phases were collected, combined and dried over magnesium sulfate and concentrated to dryness in vacuo, and finally the residue was purified by column chromatography (silica gel, hexane-ethyl acetate, 10: 2) to give 1.64g of stable isotope-labeled 4,4' -benzidine-13C12H8
Example 3
The embodiment of the invention provides a method for synthesizing stable isotope labeled benzidine, which comprises the following steps:
s1, to a 250mL round bottom flask containing 50mL acetonitrile (AcCN), aniline (991mg, 10.0mmol) was added followed by NH4OAc (77.1mg, 1.0mmol), N-bromosuccinimide (NBS, 1.96g, 11.0mmol) are added, the mixture is stirred at room temperature for 10min, after the reaction is completed, the reaction mixture is concentrated to dryness by a rotary evaporator, 25ml of saturated sodium bicarbonate solution is added, then ethyl acetate (25ml for 3 times) is used for extraction, the obtained extracts are separated and the organic phase is collected, anhydrous sodium sulfate (30 g) is added after combination for drying (room temperature, 1-2 h), then the mixture is concentrated to dryness by a rotary evaporator, finally the residue is purified by column chromatography (silica gel, hexane-ethyl acetate, 10: 1) to obtain 1.62g of light brown solid 4-bromoaniline-13C6H4。MS:179.6(MH+);1H NMR(CDCl3)δ: 7.32(m,JC-H=164Hz,1H),6.90(m,JC-H=164Hz,1H),6.69(m,JC-H= 160,Hz,1H),6.30(m,JC-H=160Hz,1H);13C NMR(CDCl3)δ:148.0(dt, J=7.8,59Hz),131.2(dt,J=6.5,63Hz),115.7(dt,J=6.5,63Hz),105.8(dt, J=9.4,63Hz)。
S2, under the protection of nitrogen, adding 1.62g of 4-bromoaniline into a 250ml round-bottom flask containing 35ml of absolute ethyl alcohol13C6H4And 3.47g bis (pinacolato) diboron, then introducing nitrogen into the resulting solution for 5min, then adding palladium-carbon (10%, 968.0mg) followed by potassium acetate (2.68g), continuing the nitrogen introduction for 5min, and then adding the mixture to the reaction vesselHeating to 60 deg.C, stirring for 8h, cooling the reactor to room temperature, filtering the reaction mixture, concentrating the filtrate under reduced pressure, adding saturated sodium bicarbonate solution 25ml, extracting the residue with dichloromethane (25ml 3 times), separating the obtained extracts and collecting the organic phases, combining, drying over magnesium sulfate and vacuum concentrating to dryness, and purifying the residue by column chromatography (silica gel, hexane-ethyl acetate, 10: 2) to obtain 1.73g of stable isotope labeled 4,4' -benzidine-13C12H8。MS:197.1(MH+);1H NMR(CD3OD)δ:7.17(4H,ddd,J=8.6,1.2,0.5Hz),7.78(4H,ddd,J =8.6,1.8,0.5Hz)。
It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. The protection scope of the present invention should be subject to the appended claims.

Claims (9)

1.一种稳定同位素标记的联苯胺的合成方法,其特征在于,1. a synthetic method of stable isotope-labeled benzidine, is characterized in that, 所述稳定同位素标记的联苯胺的分子结构式如下:The molecular structural formula of the stable isotope-labeled benzidine is as follows:
Figure FDA0003419511660000011
Figure FDA0003419511660000011
其合成方法包括:Its synthesis method includes: S1、将稳定同位素标记的苯胺与N-溴代丁二酰亚胺置于有机溶剂中混合,加入催化剂后在室温下搅拌反应,反应完成后对所得到的混合物进行后处理得到4-溴苯胺-13C6H4S1. The stable isotope-labeled aniline and N-bromosuccinimide are placed in an organic solvent and mixed, and the catalyst is added and the reaction is stirred at room temperature. After the reaction is completed, the obtained mixture is subjected to post-processing to obtain 4-bromoaniline - 13 C 6 H 4 ; S2、在氮气气氛保护下,将步骤S1中得到的4-溴苯胺-13C6H4加入到含有钯/碳催化剂、乙酸钾和双(频哪醇合)二硼的乙醇溶液中,加热搅拌,反应后冷却至室温,并对得到的反应物进行再处理,即得稳定同位素标记的联苯胺。S2, under the protection of nitrogen atmosphere, the 4 -bromoaniline - 13C6H4 obtained in step S1 is added in the ethanolic solution containing palladium/carbon catalyst, potassium acetate and bis(pinacol) diboron, heated Stir, cool to room temperature after the reaction, and reprocess the obtained reactant to obtain stable isotope-labeled benzidine.
2.根据权利要求1所述的稳定同位素标记的联苯胺的合成方法,其特征在于,2. the synthetic method of the stable isotope-labeled benzidine according to claim 1, is characterized in that, 步骤S1中,In step S1, 所述催化剂为乙酸铵,优选地,所述催化剂的加入的摩尔量为稳定同位素标记的苯胺的0.08-0.125倍;The catalyst is ammonium acetate, and preferably, the molar amount of the catalyst added is 0.08-0.125 times that of the stable isotope-labeled aniline; 和/或,所述搅拌反应的时间为10-60min。And/or, the time of the stirring reaction is 10-60min. 3.根据权利要求1所述的稳定同位素标记的联苯胺的合成方法,其特征在于,3. the synthetic method of the stable isotope-labeled benzidine according to claim 1, is characterized in that, 步骤S1中,In step S1, 所述N-溴代丁二酰亚胺的加入的摩尔量为稳定同位素标记的苯胺的1.0-1.15倍;The added molar amount of the N-bromosuccinimide is 1.0-1.15 times that of the stable isotope-labeled aniline; 和/或,所述有机溶剂为乙腈。And/or, the organic solvent is acetonitrile. 4.根据权利要求1-3任一项所述的稳定同位素标记的联苯胺的合成方法,其特征在于,4. the synthetic method of the stable isotope-labeled benzidine according to any one of claims 1-3, is characterized in that, 步骤S1中,所述后处理包括:In step S1, the post-processing includes: 将反应完成后所得到的混合物进行浓缩,随后加入饱和碳酸氢钠溶液并用乙酸乙酯萃取,将得到的萃取液分离并收集有机相,干燥并浓缩,最后将残留物进行柱层析纯化,得到4-溴苯胺-13C6H4The mixture obtained after the completion of the reaction was concentrated, then saturated sodium bicarbonate solution was added and extracted with ethyl acetate, the obtained extract was separated and the organic phase was collected, dried and concentrated, and finally the residue was purified by column chromatography to obtain 4-Bromoaniline- 13 C 6 H 4 . 5.根据权利要求4所述的稳定同位素标记的联苯胺的合成方法,其特征在于,5. the synthetic method of the stable isotope-labeled benzidine according to claim 4, is characterized in that, 步骤S1中,In step S1, 将反应完成后所得到的所述混合物浓缩至干,再加入饱和碳酸氢钠溶液;The mixture obtained after the completion of the reaction is concentrated to dryness, and then saturated sodium bicarbonate solution is added; 和/或,对应于10mmol的苯胺,所述饱和碳酸氢钠溶液的加入量为20-50mL。And/or, corresponding to 10 mmol of aniline, the added amount of the saturated sodium bicarbonate solution is 20-50 mL. 6.根据权利要求1所述的稳定同位素标记的联苯胺的合成方法,其特征在于,6. the synthetic method of the stable isotope-labeled benzidine according to claim 1, is characterized in that, 步骤S2中,在所述乙醇溶液中,In step S2, in the ethanol solution, 所述钯/碳催化剂的加入的摩尔量为4-溴苯胺-13C6H4的0.01-0.1倍;The added molar amount of the palladium/carbon catalyst is 0.01-0.1 times of 4 -bromoaniline - 13C6H4 ; 和/或,所述乙酸钾的加入的摩尔量为4-溴苯胺-13C6H4的2.75-3.6倍;And/or, the added molar amount of the potassium acetate is 2.75-3.6 times of 4 - bromoaniline- 13C6H4 ; 和/或,所述双(频哪醇合)二硼的加入的摩尔量为4-溴苯胺-13C6H4的1.35-1.8倍。And/or, the molar amount of the bis(pinacol) diboron added is 1.35-1.8 times that of 4-bromoaniline- 13 C 6 H 4 . 7.根据权利要求1所述的稳定同位素标记的联苯胺的合成方法,其特征在于,7. the synthetic method of the stable isotope-labeled benzidine according to claim 1, is characterized in that, 步骤S2中,In step S2, 所述加热搅拌的温度和时间分别为55-72℃和7.5-9h。The temperature and time of the heating and stirring are respectively 55-72° C. and 7.5-9 h. 8.根据权利要求1或6或7所述的稳定同位素标记的联苯胺的合成方法,其特征在于,8. the synthetic method of the stable isotope-labeled benzidine according to claim 1 or 6 or 7, is characterized in that, 步骤S2中,In step S2, 所述再处理包括:The reprocessing includes: 将得到的反应物过滤后,取滤液并减压浓缩,随后加入饱和碳酸氢钠溶液并用二氯甲烷萃取,将得到的萃取液分离并收集有机相,干燥并浓缩,最后将残留物进行柱层析纯化,得到稳定同位素标记的联苯胺。After the obtained reactant was filtered, the filtrate was taken and concentrated under reduced pressure, then saturated sodium bicarbonate solution was added and extracted with dichloromethane, the obtained extract was separated and the organic phase was collected, dried and concentrated, and finally the residue was subjected to column layer Analytical purification to obtain stable isotope-labeled benzidine. 9.权利要求1-8任一项所述的合成方法在制备稳定同位素标记的4,4'-联苯胺-13C12H8中的应用。9. The application of the synthetic method of any one of claims 1-8 in the preparation of stable isotope-labeled 4,4'-benzidine- 13 C 12 H 8 .
CN202111557533.6A 2021-12-19 2021-12-19 Synthetic method and application of stable isotope labeled benzidine Pending CN114230470A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111557533.6A CN114230470A (en) 2021-12-19 2021-12-19 Synthetic method and application of stable isotope labeled benzidine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111557533.6A CN114230470A (en) 2021-12-19 2021-12-19 Synthetic method and application of stable isotope labeled benzidine

Publications (1)

Publication Number Publication Date
CN114230470A true CN114230470A (en) 2022-03-25

Family

ID=80758685

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111557533.6A Pending CN114230470A (en) 2021-12-19 2021-12-19 Synthetic method and application of stable isotope labeled benzidine

Country Status (1)

Country Link
CN (1) CN114230470A (en)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1490302A (en) * 2002-10-15 2004-04-21 协和化学株式会社 Benzidine compound preparing method
CN1506349A (en) * 2002-12-11 2004-06-23 中国石油化工股份有限公司 Prepn process of 4-amino diphenylamine
KR20160106238A (en) * 2015-03-02 2016-09-12 (주)부흥산업사 Novel aromatic amine derivatives for organic electroluminescent device
CN106995461A (en) * 2017-03-03 2017-08-01 中山大学 A kind of Phosphine ligands of the structure containing benzofuran and its preparation method and application
CN109467561A (en) * 2018-11-19 2019-03-15 广东工业大学 A dual-donor hole transport material containing a phenothiazine structure, a preparation method thereof, and a perovskite solar cell
CN111303011A (en) * 2018-12-12 2020-06-19 乐金显示有限公司 Organic compound, light-emitting diode and light-emitting device having the same
WO2021152435A1 (en) * 2020-01-27 2021-08-05 Hikal Limited Process for preparation of 5-bromo-1, 2, 3-trichlorobenzene

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1490302A (en) * 2002-10-15 2004-04-21 协和化学株式会社 Benzidine compound preparing method
CN1506349A (en) * 2002-12-11 2004-06-23 中国石油化工股份有限公司 Prepn process of 4-amino diphenylamine
KR20160106238A (en) * 2015-03-02 2016-09-12 (주)부흥산업사 Novel aromatic amine derivatives for organic electroluminescent device
CN106995461A (en) * 2017-03-03 2017-08-01 中山大学 A kind of Phosphine ligands of the structure containing benzofuran and its preparation method and application
CN109467561A (en) * 2018-11-19 2019-03-15 广东工业大学 A dual-donor hole transport material containing a phenothiazine structure, a preparation method thereof, and a perovskite solar cell
CN111303011A (en) * 2018-12-12 2020-06-19 乐金显示有限公司 Organic compound, light-emitting diode and light-emitting device having the same
WO2021152435A1 (en) * 2020-01-27 2021-08-05 Hikal Limited Process for preparation of 5-bromo-1, 2, 3-trichlorobenzene

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
FANGYU DU ET AL.,: "imerization of Aromatic Compounds Using Palladium-Carbon-Catalyzed Suzuki–Miyaura Cross-Coupling by One-Pot Synthesis", 《SYNLETT》, vol. 29, pages 779 - 784 *
张青山: "《有机合成反应基础》", 31 December 2004, 高等教育出版社, pages: 43 *

Similar Documents

Publication Publication Date Title
Gao et al. A highly selective fluorescent chemosensor for iron ion based on 1H-imidazo [4, 5-b] phenazine derivative
CN105315264B (en) A kind of N '-(Quinoline -2- methylene)- 7- diethylaminocoumarin -3- formylhydrazines and its preparation method and application
Adao et al. CuII–salan compounds: Synthesis, characterization and evaluation of their potential as oxidation catalysts
CN107488147A (en) A kind of fluorescence probe and preparation method and application
CN103254096B (en) A kind of synthetic method of cold labeling basic orange II
CN110590784B (en) Derivative based on pyrrolopyrroledione and preparation method and application thereof
CN113735829B (en) Fluorescent reagent for detecting organic phosphate and preparation method thereof
CN110286105B (en) A kind of fluorescent probe and preparation method thereof
CN104151327A (en) Synthesis and separation method of trans-seven-membered-cucurbituril
CN108484414B (en) Formaldehyde fluorescent probe and formaldehyde detection sheet based on tetraphenylethylene and preparation method thereof, and method of using formaldehyde detection sheet
CN107892654B (en) Isolongifolane-based fluorescent acid-base indicator and synthetic method and application thereof
CN108863984B (en) Thiazacrown ether-fluorenschiff base fluorescent molecular probe for detecting Mg2+, Fe3+, Cu2+ and preparation method
CN114230470A (en) Synthetic method and application of stable isotope labeled benzidine
CN112300107B (en) Triptycene functional material, preparation method and application thereof
CN109503604A (en) Benzimidazole benzimidazole derivative and its synthetic method
CN118652196A (en) A fluorescent probe for detecting lead ions in traditional Chinese medicine and a preparation method thereof
CN109232658B (en) A kind of chiral rhodium complex and its preparation and application
CN113173883A (en) 8-hydroxyquinoline functionalized column [5] arene, synthesis thereof and application thereof in detection and adsorption of ethylenediamine
CN111253443A (en) Preparation method and application of a class of cyclometal iridium complexes modified with electron-withdrawing groups
CN107235962A (en) A kind of enhanced fluorescence probe, its preparation method and application based on naphthalimide
CN113651821B (en) A fluorescent probe based on diketopyrrolopyrrole derivatives and its application
CN105461726B (en) The one-step method for synthesizing of the hydroxy-porphyrin of new type water-solubility eight
CN115286646A (en) Probe for detecting amine compound residues in polyurethane, preparation method and application thereof
CN116068110B (en) Synthesis and application of azide mass spectrometry probe
CN113979890A (en) A kind of Schiff base ligand and its preparation method and application of multinuclear rare earth complex

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
CB02 Change of applicant information
CB02 Change of applicant information

Address after: Room 801, building 5, Changzhou inspection and testing industrial park, Changzhou City, Jiangsu Province 213000

Applicant after: Changzhou Manhag Testing Technology Co.,Ltd.

Address before: 213000 Black Peony Science Park, Tianning District, Changzhou City, Jiangsu Province

Applicant before: Manhag Testing Technology Co.,Ltd.

TA01 Transfer of patent application right
TA01 Transfer of patent application right

Effective date of registration: 20230919

Address after: 101100 second floor, building 63, No. 15, Jingsheng South 4th Street, Jinqiao Science and technology industrial base, Tongzhou Park, Zhongguancun Science and Technology Park, Tongzhou District, Beijing

Applicant after: Beijing Manhattan Biotechnology Co.,Ltd.

Address before: Room 801, building 5, Changzhou inspection and testing industrial park, Changzhou City, Jiangsu Province 213000

Applicant before: Changzhou Manhag Testing Technology Co.,Ltd.

RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20220325