CN101973910A - Method for synthesizing triphenylmethane compounds marked with stable isotopes - Google Patents
Method for synthesizing triphenylmethane compounds marked with stable isotopes Download PDFInfo
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Abstract
The invention relates to a method for synthesizing triphenylmethane compounds marked with stable isotopes. In the method, methanol marked by a stable isotope and phenylamine undergo a methylation reaction to form N-N-dimethylaniline; the N-N-dimethylaniline is reacted with a bonding agent and crystalviolet lactone or Michler's ketone to form a product; and the product is oxidized to form recessive crystal violet marked with the stable isotope or crystal violet, wherein the recessive crystal violet marked with the stable isotope or crystal violet is the product of the invention. Compared with the prior art, the method has the advantages that: after the crystal violet marked with the stable isotope and recessive crystal violet, which is prepared by the method, are separated or purified, the chemical purity reaches over 99 percent, and the isotope abundance reaches over 98 percent atom; and the crystal violet marked with the stable isotope and recessive crystal violet can meet the requirements of veterinary medicine residue detection in field of food safety.
Description
Technical field
The present invention relates to a kind of synthetic method of compound isotopically labelled, especially relate to a kind of synthetic method of cold labeling Synthesis of diaminodiphenyl.
Background technology
Synthesis of diaminodiphenyl such as Viola crystallina, leuco crystal violet, as antimycotic, sterilizing agent and antiparasitic once were widely used in the fish farming industry.Recent study shows, effect such as that Viola crystallina, leuco crystal violet etc. all have is carcinogenic, teratogenesis, mutagenesis.At present, European developed country and China forbid that all Viola crystallina and leuco crystal violet use in fishery cultivating and fish transportation.For preventing the residual food chains that enter of Synthesis of diaminodiphenyl such as Viola crystallina, leuco crystal violet, culturist and supervision department of government need a kind of can be fast, accurately also very sensitive technology detects it.
Mass spectrum is used gradually in all kinds of residue detection and is popularized as present detection technique with fastest developing speed, becomes the detecting instrument of analysis and confirmatory test chamber indispensability.Because mass spectrum can provide qualitative and quantitative information simultaneously, so developed country detects with mass spectroscopy for residual all requirement the in food, the feed, and relevant criterion carried out the 2002/657/EC instruction of detailed regulation such as European Union.
Stable isotope dilution mass spectrometry IDMS (Isotope Dilution Mass Spectrometry) adopts with measured matter to have the compound of cold labeling of same molecular structure as internal standard substance matter, (LC/MS) detects with high resolution liquid chromatography-GC-MS, measures the ionic ratio of respective quality number and reaches accurate quantitative purpose with the odds ratio of standard by mass spectrograph.Adopt the interior mark of isotropic substance can effectively eliminate sample caused rate of recovery difference in the pre-treatment step of chemistry and physics, thereby avoid because the deviation that the loss of sample preparation process causes detected result.
The ability of the highly sensitive of this specific character of target and LC/MS and processing complex sample combines in the stable isotope, makes chromatogram/isotopic dilution mass-spectrometric technique be acknowledged as a kind of pedestal method of measuring trace and trace organic substance.And cold labeling Synthesis of diaminodiphenyl cold labeling Viola crystallina, cold labeling procrypsis crystalline are succeeded in developing, to provide standard reagent for detection by quantitative Viola crystallina, leuco crystal violet more accurately, thereby be China's food safety field detection of veterinary drugs in food service effectively.
Summary of the invention
Purpose of the present invention is exactly to provide the synthetic method that a kind of process is simple, separate the easy cold labeling Synthesis of diaminodiphenyl of purifying for the defective that overcomes above-mentioned prior art existence.
Purpose of the present invention can be achieved through the following technical solutions:
A kind of synthetic method of cold labeling Synthesis of diaminodiphenyl, it is characterized in that, this method is to utilize the methyl alcohol of cold labeling and aniline to generate N through methylation reaction, accelerine, with reoxidize the Viola crystallina that obtains cold labeling after coupler, Michaelis alcohol or the michaelis ketone reaction, be product.
The methyl alcohol of described cold labeling is isotropic substance
13The methyl alcohol of the methyl alcohol of C mark or isotope D mark.
This method specifically may further comprise the steps:
(1) with isotropic substance
13The methyl alcohol of C mark and aniline are to mix in 2: 1～4: 1 to be placed in the basic solution in molar ratio, add catalyzer again, and control reaction temperature is 30～150 ℃, and stirring reaction 3～5h obtains
13The N of C mark, accelerine;
(2) step (1) is obtained
13The N of C mark, accelerine and coupler mixed to be placed in the liquid phase environment in 3: 1～1: 4, and control reaction temperature is 60～130 ℃, and stirring reaction 3～5h obtains
13The leuco crystal violet of C mark;
(3) step (2) is obtained
13The leuco crystal violet of C mark places acid liquid phase environment, adds catalyzer again, and under nitrogen and oxygen atmosphere, control reaction temperature is 10～80 ℃, and stirring reaction 3～5h obtains
13The Viola crystallina of C mark is product.
Preferred 2: 1～3: 1 of the methyl alcohol in the described step (1) and the mol ratio of aniline, the concentration of described basic solution is 40～60wt%, wherein solute is selected from ammoniacal liquor, NaOH, Na
2CO
3, KOH or K
2CO
3In one or more, preferred NaOH or KOH, solvent is selected from water, tetrahydrofuran (THF), one or more mixing in dioxane or the acetone, preferably water, tetrahydrofuran (THF) or dioxane, described catalyzer is selected from tri-n-octyl methyl ammonium chloride, Dodecyl trimethyl ammonium chloride, benzyltriethylammoinium chloride, Tetrabutyl amonium bromide, in tetrabutylammonium chloride or the 4-butyl ammonium hydrogen sulfate one or more, preferred Dodecyl trimethyl ammonium chloride, benzyltriethylammoinium chloride, Tetrabutyl amonium bromide or tetrabutylammonium chloride, the weight ratio of catalyzer and aniline is 0.01: 1～0.4: 1, preferred 60～120 ℃ of temperature of reaction.
In the described step (2)
13The N of C mark, preferred 1: 1～1: 3 of the mol ratio of accelerine and coupler, described coupler comprises formaldehyde, Paraformaldehyde 96 or FORMAMIDINE ACETATE, preferred FORMAMIDINE ACETATE or Paraformaldehyde 96, described liquid phase environment is selected from one or more in methyl alcohol, ethanol, acetone, acetate or the diacetyl oxide, in preferred acetone, acetate or the diacetyl oxide one or more, preferred 70～120 ℃ of temperature of reaction.
Acid liquid phase environment in the described step (3) is selected from one or more in acetate, diacetyl oxide, acetone, acetonitrile or the dioxane, one or more in preferred acetate, diacetyl oxide, acetone or the acetonitrile, and described catalyzer is selected from CuBr, FeCl
3, CuCl or AlCl
3In one or more, preferred FeCl
3Or CuCl, catalyzer with
13The weight ratio of the leuco crystal violet of C mark is 0.01: 1～0.1: 1, preferred 30～50 ℃ of temperature of reaction.
This method is further comprising the steps of:
(1) be to mix in 2: 1～4: 1 to be placed in the basic solution in molar ratio with the methyl alcohol of isotope D mark and aniline, add catalyzer again, control reaction temperature is 30～150 ℃, and stirring reaction 3～5h obtains the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and Michaelis alcohol mixed to be placed in the liquid phase environment in 1: 1～1: 4, added catalyzer again, control reaction temperature is 50～130 ℃, stirring reaction 3～5h obtains the leuco crystal violet of D mark, is product.
The N of the D mark in the described step (2), preferred 1: 1～1: 3 of the mol ratio of accelerine and Michaelis alcohol, described liquid phase environment is one or more in benzene, toluene or the dimethylbenzene, described catalyzer is one or more in p-methyl benzenesulfonic acid, hydrochloric acid, sulfuric acid or the nitric acid, preferably sulfuric acid or p-methyl benzenesulfonic acid, the N of catalyzer and D mark, the weight ratio of accelerine is 0.01: 1～0.2: 1, preferred 60～120 ℃ of temperature of reaction.
This method is further comprising the steps of:
(1) be to mix in 2: 1～4: 1 to be placed in the basic solution in molar ratio with the methyl alcohol of isotope D mark and aniline, add catalyzer again, control reaction temperature is 30～150 ℃, and stirring reaction 3～5h obtains the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and michaelis ketone mixed to be placed in the liquid phase environment in 1: 1～1: 5, added chlorination reagent again, control reaction temperature is 20～120 ℃, stirring reaction 3～5h obtains the Viola crystallina of D mark, is product.
The N of the D mark in the described step (2), preferred 1: 1～1: 4 of the mol ratio of accelerine and michaelis ketone, described liquid phase environment is one or more of methylene dichloride, trichloromethane or acetonitrile, described chlorination reagent is phosphorus oxychloride or sulfur oxychloride, preferred phosphorus oxychloride, the N of chlorination reagent and D mark, the weight ratio of accelerine is 5: 1～20: 1, preferred 50～100 ℃ of temperature of reaction.
Compared with prior art, the present invention has the following advantages:
(1) the present invention adopts procedure simple, stable isotope atom utilization height;
(2) the easily separated purification of product of the present invention, product chemical purity are more than 99%, and isotopic abundance can fully satisfy the demand of food safety field detection of veterinary drugs in food more than 98%atom;
(3) the present invention has good economy and use value.
Embodiment
The present invention is described in detail below in conjunction with specific embodiment.
Embodiment 1
A kind of cold labeling leuco crystal violet-
13C
6-methyl, Viola crystallina-
13C
6The preparation method of-methyl, the process of its preparation method is as follows:
This method specifically may further comprise the steps:
1, cold labeling N, accelerine-
13C
2The preparation of-methyl
In three mouthfuls of burnings of 100mL, add 4.65g aniline (0.05mol), 3.304g
13CH
3The sodium hydroxide solution of OH (0.1mol), 30mL50%, 0.75g Tetrabutyl amonium bromide, control reaction temperature is 70 ℃, stirring reaction is 4 hours under the normal pressure, separate, purify N, accelerine-
13C
2-methyl 4.046g, yield 65.7%.GC detects, purity 〉=99%; Mass spectrometric detection, abundance 〉=98%atom
13C.
2, the cold labeling leuco crystal violet-
13C
6The preparation of-methyl
In adding, two mouthfuls of burnings of 50mL go into 3.077gN, accelerine-
13C
2-methyl (0.025mol), 3mL acetate, 3mL acetone, 3mL are heated to 90 ℃ under the agitation condition, add 2.252g Paraformaldehyde 96 (0.075mol), keep 90 ℃ of reactions of temperature of reaction 4 hours, through separate, purify, after the oven dry the 3.024g leuco crystal violet-
13C
6-methyl, yield 95.6%.HPLC detects, purity 〉=99%; Mass spectrometric detection, abundance 〉=98%atom
13C.
3, cold labeling Viola crystallina-
13C
6The preparation of-methyl
Adding 4.744g leuco crystal violet in two mouthfuls of flasks of 100mL-
13C
6-methyl (0.0125mol), 25g acetate, 25g ethanamide, 2.5ml acetone, 0.1gFeCl
3, 4 droplets dense HCl, 0.2g tetrachlorobenzoquinone and 2ml water, under nitrogen blanket and oxygen spray, be heated to 50 ℃ and kept 4 hours, reaction mixture is poured in the mixture of 250ml ammoniacal liquor and 250ml ice, stirred slurries 1 hour, filter cake is with the washing of 25ml weak ammonia, after the oven dry 4.719g Viola crystallina-
13C
6-methyl.Yield 91.2%.HPLC detects, purity 〉=99%; Mass spectrometric detection, abundance 〉=98%atom
13C.
Embodiment 2
A kind of cold labeling leuco crystal violet-D
6-methyl, Viola crystallina-D
6The preparation method of-methyl, its preparation method may further comprise the steps:
1, cold labeling N, accelerine-D
6The preparation of-methyl
In three mouthfuls of burnings of 100mL, add 4.65g aniline (0.05mol), 3.604gCD
3The sodium hydroxide solution of OD (0.1mol), 30mL50%, 0.75g Tetrabutyl amonium bromide, control reaction temperature is 70 ℃, stirring reaction is 4 hours under the normal pressure, separate purify N, accelerine-D
6-methyl 4.203g, yield 66.1%.GC detects, purity 〉=99%; Mass spectrometric detection, abundance 〉=99%atom D.
2, cold labeling leuco crystal violet-D
6The preparation of-methyl
In adding, two mouthfuls of burnings of 100mL go into 3.180gN, accelerine-D6-methyl (0.025mol), 13.518g Michaelis alcohol (0.050mol), 60mL benzene, the 0.2g vitriol oil, be heated to backflow under the agitation condition, reacted 4 hours, after separating, purify, drying, get 4.754g leuco crystal violet-D
6-methyl, yield 50.1%.HPLC detects, purity 〉=99%; Mass spectrometric detection, abundance 〉=99.5%atomD.
3, cold labeling Viola crystallina-D
6The preparation of-methyl
In adding, two mouthfuls of burnings of 100mL go into 3.180gN, accelerine-D
6-methyl (0.025mol), 20.127g michaelis ketone (0.075mol), 30mLPOCl
3, the 20mL trichloromethane, be heated to backflow under the agitation condition, reacted 4 hours, through separate, purify, after the oven dry 8.300g leuco crystal violet-D
6-methyl, yield 80.2%.HPLC detects, purity 〉=99%; Mass spectrometric detection, abundance 〉=99.5%atom D.
Its chemical reaction process is as follows:
Embodiment 3
A kind of isotropic substance
13The synthetic method of C mark Synthesis of diaminodiphenyl, this method specifically may further comprise the steps:
(1) with isotropic substance
13The methyl alcohol of C mark and aniline are to mix at 2: 1 to be placed in the NaOH aqueous solution that concentration is 40wt% in molar ratio, add the catalyzer tri-n-octyl methyl ammonium chloride again, the weight ratio of catalyzer and aniline is 0.01: 1, and control reaction temperature is 30 ℃, stirring reaction 5h obtains
13The N of C mark, accelerine;
(2) step (1) is obtained
13The N of C mark, accelerine and Paraformaldehyde 96 mix to be placed in methyl alcohol and the alcoholic acid mixing solutions at 3: 1, and control reaction temperature is 60 ℃, and stirring reaction 5h obtains
13The leuco crystal violet of C mark;
(3) step (2) is obtained
13The leuco crystal violet of C mark places the mixing solutions of acetate and diacetyl oxide, adds CuBr again, CuBr with
13The weight ratio of the leuco crystal violet of C mark is 0.01: 1, and under nitrogen and oxygen atmosphere, control reaction temperature is 10 ℃, and stirring reaction 5h obtains
13The Viola crystallina of C mark is product.
Embodiment 4
A kind of isotropic substance
13The synthetic method of C mark Synthesis of diaminodiphenyl, this method specifically may further comprise the steps:
(1) with isotropic substance
13The methyl alcohol of C mark and aniline are to mix at 3: 1 to be placed on the Na that concentration is 50wt% in molar ratio
2CO
3Dioxane solution in, add the catalyzer benzyltriethylammoinium chloride again, the weight ratio of catalyzer and aniline is 0.1: 1, control reaction temperature is 120 ℃, stirring reaction 4h obtains
13The N of C mark, accelerine;
(2) step (1) is obtained
13The N of C mark, accelerine and FORMAMIDINE ACETATE are to mix at 1: 1 to be placed in the acetone in molar ratio, and control reaction temperature is 120 ℃, and stirring reaction 4h obtains
13The leuco crystal violet of C mark;
(3) step (2) is obtained
13The leuco crystal violet of C mark places acetonitrile, adds catalyst Fe Cl again
3, FeCl
3With
13The weight ratio of the leuco crystal violet of C mark is 0.09: 1, and under nitrogen and oxygen atmosphere, control reaction temperature is 50 ℃, and stirring reaction 4h obtains
13The Viola crystallina of C mark is product.
Embodiment 5
A kind of isotropic substance
13The synthetic method of C mark Synthesis of diaminodiphenyl, this method specifically may further comprise the steps:
(1) with isotropic substance
13The methyl alcohol of C mark and aniline are to mix at 4: 1 to be placed in the tetrahydrofuran solution of KOH that concentration is 60wt% in molar ratio, add the catalyzer tri-n-octyl methyl ammonium chloride again, the weight ratio of catalyzer and aniline is 0.02: 1, and control reaction temperature is 150 ℃, stirring reaction 3h obtains
13The N of C mark, accelerine;
(2) step (1) is obtained
13The N of C mark, accelerine and Paraformaldehyde 96 mix to be placed in methyl alcohol and the alcoholic acid mixing solutions at 1: 4, and control reaction temperature is 130 ℃, and stirring reaction 3h obtains
13The leuco crystal violet of C mark;
(3) leuco crystal violet of the 13C mark that step (2) is obtained places the mixing solutions of acetate and diacetyl oxide, adds CuBr again, CuBr with
13The weight ratio of the leuco crystal violet of C mark is 0.01: 1, and under nitrogen atmosphere, control reaction temperature is 80 ℃, and stirring reaction 3h obtains the Viola crystallina of 13C mark, is product.
Embodiment 6
A kind of synthetic method of Synthesis of diaminodiphenyl of isotope D mark, this method specifically may further comprise the steps:
(1) be to mix at 2: 1 to be placed in the NaOH aqueous solution that concentration is 40wt% in molar ratio with the methyl alcohol of isotope D mark and aniline, add the catalyzer tri-n-octyl methyl ammonium chloride again, the weight ratio of catalyzer and aniline is 0.01: 1, control reaction temperature is 30 ℃, stirring reaction 5h, obtain the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine mixed with Michaelis alcohol and is placed in the toluene in 1: 1 in molar ratio, add the catalyzer p-methyl benzenesulfonic acid again, the N of catalyzer and D mark, the weight ratio of accelerine is 0.01: 1, and control reaction temperature is 50 ℃, stirring reaction 5h, obtain the leuco crystal violet of D mark, be product.
Embodiment 7
A kind of synthetic method of Synthesis of diaminodiphenyl of isotope D mark, this method specifically may further comprise the steps:
(1) be to mix at 3: 1 to be placed on the Na that concentration is 50wt% in molar ratio with the methyl alcohol of coordination D mark and aniline
2CO
3Dioxane solution in, add the catalyzer benzyltriethylammoinium chloride again, the weight ratio of catalyzer and aniline is 0.4: 1, control reaction temperature is 120 ℃, stirring reaction 4h obtains the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and Michaelis alcohol are to mix in the mixture that be placed on toluene and dimethylbenzene at 1: 3 in molar ratio, add nitric acid again as catalyzer, the N of catalyzer and D mark, the weight ratio of accelerine is 0.2: 1, and control reaction temperature is 60 ℃, stirring reaction 4h, obtain the leuco crystal violet of D mark, be product.
Embodiment 8
A kind of synthetic method of Synthesis of diaminodiphenyl of isotope D mark, this method specifically may further comprise the steps:
(1) be to mix at 4: 1 to be placed in the tetrahydrofuran solution of KOH that concentration is 60wt% in molar ratio with the methyl alcohol of isotope D mark and aniline, add the catalyzer tri-n-octyl methyl ammonium chloride again, the weight ratio of catalyzer and aniline is 0.2: 1, control reaction temperature is 150 ℃, stirring reaction 3h, obtain the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and Michaelis alcohol are to mix at 1: 4 to be placed in the benzene in molar ratio, add sulfuric acid again as catalyzer, control reaction temperature is 130 ℃, the N of catalyzer and D mark, the weight ratio of accelerine is 0.2: 1, stirring reaction 3h, obtain the leuco crystal violet of D mark, be product.
Embodiment 9
A kind of synthetic method of Synthesis of diaminodiphenyl of isotope D mark, this method specifically may further comprise the steps:
(1) be to mix at 2: 1 to be placed in the NaOH aqueous solution that concentration is 40wt% in molar ratio with the methyl alcohol of isotope D mark and aniline, add the catalyzer tri-n-octyl methyl ammonium chloride again, the weight ratio of catalyzer and aniline is 0.02: 1, control reaction temperature is 30 ℃, stirring reaction 5h, obtain the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and michaelis ketone are to mix at 1: 1 to be placed in the methylene dichloride in molar ratio, add phosphorus oxychloride again, the N of phosphorus oxychloride and D mark, the weight ratio of accelerine is 5: 1, and control reaction temperature is 20 ℃, stirring reaction 5h, obtain the Viola crystallina of D mark, be product.
Embodiment 10
A kind of synthetic method of Synthesis of diaminodiphenyl of isotope D mark, this method specifically may further comprise the steps:
(1) be to mix at 3: 1 to be placed on the Na that concentration is 50wt% in molar ratio with the methyl alcohol of coordination D mark and aniline
2CO
3Dioxane solution in, add the catalyzer benzyltriethylammoinium chloride again, the weight ratio of catalyzer and aniline is 0.02: 1, control reaction temperature is 120 ℃, stirring reaction 4h obtains the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and michaelis ketone are to mix in the mixing solutions that be placed on methylene dichloride and trichloromethane at 1: 4 in molar ratio, add phosphorus oxychloride again, the N of phosphorus oxychloride and D mark, the weight ratio of accelerine is 10: 1, and control reaction temperature is 100 ℃, stirring reaction 4h, obtain the Viola crystallina of D mark, be product.
Embodiment 11
A kind of synthetic method of Synthesis of diaminodiphenyl of isotope D mark, this method specifically may further comprise the steps:
(1) be to mix at 4: 1 to be placed in the tetrahydrofuran solution of KOH that concentration is 60wt% in molar ratio with the methyl alcohol of isotope D mark and aniline, add the catalyzer tri-n-octyl methyl ammonium chloride again, the weight ratio of catalyzer and aniline is 0.2: 1, control reaction temperature is 150 ℃, stirring reaction 3h, obtain the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and michaelis ketone are to mix at 1: 5 to be placed in the acetonitrile in molar ratio, add sulfur oxychloride again, the N of sulfur oxychloride and D mark, the weight ratio of accelerine is 7: 1, and control reaction temperature is 120 ℃, stirring reaction 3h, obtain the Viola crystallina of D mark, be product.
Embodiment 12
A kind of synthetic method of Synthesis of diaminodiphenyl of isotope D mark, this method specifically may further comprise the steps:
(1) be to mix at 3: 1 to be placed on the Na that concentration is 50wt% in molar ratio with the methyl alcohol of coordination D mark and aniline
2CO
3Dioxane solution in, add the catalyzer benzyltriethylammoinium chloride again, the weight ratio of catalyzer and aniline is 0.02: 1, control reaction temperature is 120 ℃, stirring reaction 4h obtains the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and michaelis ketone are to mix in the mixing solutions that be placed on methylene dichloride and trichloromethane at 1: 4 in molar ratio, add phosphorus oxychloride again, the N of phosphorus oxychloride and D mark, the weight ratio of accelerine is 20: 1, and control reaction temperature is 100 ℃, stirring reaction 4h, obtain the Viola crystallina of D mark, be product.
Claims (10)
1. the synthetic method of a cold labeling Synthesis of diaminodiphenyl, it is characterized in that, this method is to utilize the methyl alcohol of cold labeling and aniline to generate N through methylation reaction, accelerine, with reoxidize recessive Viola crystallina or the Viola crystallina that obtains cold labeling after coupler, Michaelis alcohol or the michaelis ketone reaction, be product.
2. the synthetic method of a kind of cold labeling Synthesis of diaminodiphenyl according to claim 1 is characterized in that, the methyl alcohol of described cold labeling is isotropic substance
13The methyl alcohol of the methyl alcohol of C mark or isotope D mark.
3. the synthetic method of a kind of cold labeling Synthesis of diaminodiphenyl according to claim 1 is characterized in that, this method specifically may further comprise the steps:
(1) with isotropic substance
13The methyl alcohol of C mark and aniline are to mix in 2: 1～4: 1 to be placed in the basic solution in molar ratio, add catalyzer again, and control reaction temperature is 30～150 ℃, and stirring reaction 3～5h obtains
13The N of C mark, accelerine;
(2) step (1) is obtained
13The N of C mark, accelerine and coupler mixed to be placed in the liquid phase environment in 3: 1～1: 4, and control reaction temperature is 60～130 ℃, and stirring reaction 3～5h obtains
13The leuco crystal violet of C mark;
(3) step (2) is obtained
13The leuco crystal violet of C mark places acid liquid phase environment, adds catalyzer again, and under nitrogen and oxygen atmosphere, control reaction temperature is 10～80 ℃, and stirring reaction 3～5h obtains
13The Viola crystallina of C mark is product.
4. the synthetic method of a kind of cold labeling Synthesis of diaminodiphenyl according to claim 1 is characterized in that, this method is further comprising the steps of:
(1) be to mix in 2: 1～4: 1 to be placed in the basic solution in molar ratio with the methyl alcohol of isotope D mark and aniline, add catalyzer again, control reaction temperature is 30～150 ℃, and stirring reaction 3～5h obtains the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and Michaelis alcohol mixed to be placed in the liquid phase environment in 1: 1～1: 4, added catalyzer again, control reaction temperature is 50～130 ℃, stirring reaction 3～5h obtains the leuco crystal violet of D mark, is product.
5. the synthetic method of a kind of cold labeling Synthesis of diaminodiphenyl according to claim 1 is characterized in that, this method is further comprising the steps of:
(1) be to mix in 2: 1～4: 1 to be placed in the basic solution in molar ratio with the methyl alcohol of isotope D mark and aniline, add catalyzer again, control reaction temperature is 30～150 ℃, and stirring reaction 3～5h obtains the N of D mark, accelerine;
(2) N of the D mark that step (1) is obtained, accelerine and michaelis ketone mixed to be placed in the liquid phase environment in 1: 1～1: 5, added chlorination reagent again, control reaction temperature is 20～120 ℃, stirring reaction 3～5h obtains the Viola crystallina of D mark, is product.
6. according to the synthetic method of claim 3 or 4 or 5 described a kind of cold labeling Synthesis of diaminodiphenyl, it is characterized in that, preferred 2: 1～3: 1 of the methyl alcohol in the described step (1) and the mol ratio of aniline, the concentration of described basic solution is 40～60wt%, and wherein solute is selected from ammoniacal liquor, NaOH, Na
2CO
3, KOH or K
2CO
3In one or more, preferred NaOH or KOH, solvent is selected from water, tetrahydrofuran (THF), one or more mixing in dioxane or the acetone, preferably water, tetrahydrofuran (THF) or dioxane, described catalyzer is selected from tri-n-octyl methyl ammonium chloride, Dodecyl trimethyl ammonium chloride, benzyltriethylammoinium chloride, Tetrabutyl amonium bromide, in tetrabutylammonium chloride or the 4-butyl ammonium hydrogen sulfate one or more, preferred Dodecyl trimethyl ammonium chloride, benzyltriethylammoinium chloride, Tetrabutyl amonium bromide or tetrabutylammonium chloride, the weight ratio of catalyzer and aniline is 0.01: 1～0.4: 1, preferred 60～120 ℃ of temperature of reaction.
7. the synthetic method of a kind of cold labeling Synthesis of diaminodiphenyl according to claim 3 is characterized in that, in the described step (2)
13The N of C mark, preferred 1: 1～1: 3 of the mol ratio of accelerine and coupler, described coupler comprises formaldehyde, Paraformaldehyde 96 or FORMAMIDINE ACETATE, preferred FORMAMIDINE ACETATE or Paraformaldehyde 96, described liquid phase environment is selected from one or more in methyl alcohol, ethanol, acetone, acetate or the diacetyl oxide, in preferred acetone, acetate or the diacetyl oxide one or more, preferred 70～120 ℃ of temperature of reaction.
8. the synthetic method of a kind of cold labeling Synthesis of diaminodiphenyl according to claim 3, it is characterized in that, acid liquid phase environment in the described step (3) is selected from one or more in acetate, diacetyl oxide, acetone, acetonitrile or the dioxane, in preferred acetate, diacetyl oxide, acetone or the acetonitrile one or more, described catalyzer is selected from CuBr, FeCl
3, CuCl or AlCl
3In one or more, preferred FeCl
3Or CuCl, catalyzer with
13The weight ratio of the leuco crystal violet of C mark is 0.01: 1～0.1: 1, preferred 30～50 ℃ of temperature of reaction.
9. the synthetic method of a kind of cold labeling Synthesis of diaminodiphenyl according to claim 4, it is characterized in that, the N of the D mark in the described step (2), preferred 1: 1～1: 3 of the mol ratio of accelerine and Michaelis alcohol, described liquid phase environment is a benzene, in toluene or the dimethylbenzene one or more, described catalyzer is a p-methyl benzenesulfonic acid, hydrochloric acid, in sulfuric acid or the nitric acid one or more, preferably sulfuric acid or p-methyl benzenesulfonic acid, the N of catalyzer and D mark, the weight ratio of accelerine is 0.01: 1～0.2: 1, preferred 60～120 ℃ of temperature of reaction.
10. the synthetic method of a kind of cold labeling Synthesis of diaminodiphenyl according to claim 5, it is characterized in that, the N of the D mark in the described step (2), preferred 1: 1～1: 4 of the mol ratio of accelerine and michaelis ketone, described liquid phase environment is one or more of methylene dichloride, trichloromethane or acetonitrile, described chlorination reagent is phosphorus oxychloride or sulfur oxychloride, preferred phosphorus oxychloride, the N of chlorination reagent and D mark, the weight ratio of accelerine is 5: 1～20: 1, preferred 50～100 ℃ of temperature of reaction.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102796025A (en) * | 2012-08-29 | 2012-11-28 | 上海化工研究院 | Synthesis method for stable isotope labeled malachite green |
| CN102796009A (en) * | 2012-08-29 | 2012-11-28 | 上海化工研究院 | Synthesis method for stable isotope labeled leucomalachite green |
| CN103012159A (en) * | 2011-09-27 | 2013-04-03 | 北大方正集团有限公司 | Preparation method of N, N-diethyl aniline |
| CN110396303A (en) * | 2019-07-11 | 2019-11-01 | 维思普新材料（苏州）有限公司 | A kind of preparation and application of triarylmethane class compound |
| CN110694637A (en) * | 2019-10-14 | 2020-01-17 | 大连第一有机化工有限公司 | Preparation method of supported multi-element metal oxide oxidation catalyst |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101451999A (en) * | 2008-01-16 | 2009-06-10 | 北京中德大地食品安全技术开发有限责任公司 | Indirectly racing ELISA kit for detecting leuco malachite green |
-
2010
- 2010-10-14 CN CN 201010506103 patent/CN101973910B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101451999A (en) * | 2008-01-16 | 2009-06-10 | 北京中德大地食品安全技术开发有限责任公司 | Indirectly racing ELISA kit for detecting leuco malachite green |
Non-Patent Citations (2)
| Title |
|---|
| 徐大刚等: "稳定同位素技术的研究与发展", 《中国核科学技术进展报告－中国核学会2009年学术年会论文集》 * |
| 韩菊泉: "结晶紫合成工艺研究", 《安徽化工》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012159A (en) * | 2011-09-27 | 2013-04-03 | 北大方正集团有限公司 | Preparation method of N, N-diethyl aniline |
| CN102796025A (en) * | 2012-08-29 | 2012-11-28 | 上海化工研究院 | Synthesis method for stable isotope labeled malachite green |
| CN102796009A (en) * | 2012-08-29 | 2012-11-28 | 上海化工研究院 | Synthesis method for stable isotope labeled leucomalachite green |
| CN102796025B (en) * | 2012-08-29 | 2014-11-26 | 上海化工研究院 | Synthesis method for stable isotope labeled malachite green |
| CN110396303A (en) * | 2019-07-11 | 2019-11-01 | 维思普新材料（苏州）有限公司 | A kind of preparation and application of triarylmethane class compound |
| CN110396303B (en) * | 2019-07-11 | 2023-11-07 | 维思普新材料（苏州）有限公司 | Preparation and application of triarylmethane compound |
| CN110694637A (en) * | 2019-10-14 | 2020-01-17 | 大连第一有机化工有限公司 | Preparation method of supported multi-element metal oxide oxidation catalyst |
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