CN105199423A - Synthesizing method for prohibited pigment labeled by stable isotope - Google Patents

Synthesizing method for prohibited pigment labeled by stable isotope Download PDF

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CN105199423A
CN105199423A CN201510527201.1A CN201510527201A CN105199423A CN 105199423 A CN105199423 A CN 105199423A CN 201510527201 A CN201510527201 A CN 201510527201A CN 105199423 A CN105199423 A CN 105199423A
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reaction
stable isotope
mark
mol ratio
pigment
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CN105199423B (en
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杨维成
王浩然
罗勇
杨超
方超
李美华
盛立彦
潘洁
孙雯
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Shanghai Research Institute of Chemical Industry SRICI
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Shanghai Research Institute of Chemical Industry SRICI
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Abstract

The invention relates to a synthesizing method for a prohibited pigment labeled by a stable isotope. According to the synthesizing method, bromobenzene labeled by a stable isotope D or 13C is aminated and sulfonated to synthesize an intermediate sodium sulfanilate labeled by the stable isotope D or 13C, or the bromobenzene is taken as the raw materials and then aminated and sulfonated with an ammoniation reagent labeled by a stable isotope 15 N to synthesize the intermediate sodium sulfanilate labeled by the stable isotope 15N, and then diazotizing and coupling are performed to synthesize the prohibited pigment labeled by the stable isotope D or 15N or 13C. Compared with the prior art, the synthesizing method has the advantages that the process route is simple, the prohibited pigment labeled by the stable isotope is easy to synthesize, the product is easy to separate and purify, the chemical purity of the product is more than 99.0 percent, the isotope abundance is more than 98.0 percent, the requirements of trace detection in the field of food safety can be fully met, and the good economical efficiency and use value are achieved.

Description

The synthetic method of the violated pigment of a kind of cold labeling
Technical field
The invention belongs to isotope labelling techniques field, relate to the synthetic method of the violated pigment of a kind of cold labeling.
Background technology
Acid Orange II belongs to chemical dyestuff, normally golden yellow powder, therefore is commonly called as Acid orange Ⅱ, water-soluble yellow in ruddiness, add hydrochloric acid and produce brown color precipitation, adding sodium hydroxide solution is dark-brown, it is orange for being dissolved in ethanol, be dissolved in magenta in the vitriol oil, produce brown color precipitation after dilution, be mainly used in wool, silk, the dyeing of polyamide fibre and the direct printing of fabric thereof, bright in colour, good level-dyeing property, but fastness is poor, also can be used for the painted of leather, paper and biological products.Meanwhile, it is again a kind of indicator, is medically usually used in the dyeing of tissue slice.In foodstuffs industry, Acid Orange II belongs to non-food coloring, forbids adding in food.If these materials use in food-processing, may cause food poisoning after people is edible, long-term eating even can be carcinogenic.
Lemon yellow is also known as Tartrazol yellow, and chemical name is 1-(4-sulphenyl)-4-(4-sulphenyl azo)-5-pyrazolone-3-carboxylic acid trisodium salt, is water-soluble synthetic colour, in bright-coloured bright yellow, water-soluble, glycerine and propylene glycol, be slightly soluble in ethanol, be insoluble to grease.It has good thermotolerance, acid resistance, photostabilization and salt tolerance, citric acid and tartrate are stablized, but scale resistance is poor, chance alkali reddens, fade during reduction, Zeng Zuowei food color, is widely used in industries such as food, beverage, medicine, makeup, feeds, but because it has carinogenicity, now forbid for meat and processed goods (comprising internal organ processed goods), fish and processed goods, fruit and goods thereof.
But at present, have the illegal manufacturer of part, will Acid Orange II, lemon yellow add in food, this serious harm human consumer's be healthy.Therefore, for preventing Acid Orange II, lemon yellow enters field of food and works the mischief, health relevant departments need a kind of can rapidly, accurately and the technology of less error detects it, this has extremely important realistic meaning to the healthy of the people.
Stable isotope dilution mass spectrometry IDMS (IsotopeDilutionMassSpectrometry) adopts to have the compound of the cold labeling of same molecular structure as internal standard substance matter with measured matter, detect by high resolution liquid chromatography-GC-MS (LC/MS), the ratio of the ion of respective quality number is measured by mass spectrograph, and compare with the ratio of standard, and then reach the object of accurate quantitative analysis.Adopt Isotopic Internal Standard effectively can eliminate sample in the pre-treatment step of chemistry and physics, caused rate of recovery difference, thus the deviation avoiding that the loss because of sample handling processes causes detected result.
This characteristic of stable isotope dilution mass spectrometry combines with the highly sensitive of LC/MS and the ability processing complex sample, makes chromatogram/isotope dilution mass spectrometry technology be acknowledged as a kind of pedestal method measuring trace and trace organic substance.And target is succeeded in developing in cold labeling Acid Orange II, lemon yellow, standard reagent will be provided for more more accurate quantitative analysis Acid Orange II, lemon yellow, improve China's food safety detection technical system, meet the demand of China's food safety development.
Summary of the invention
Object of the present invention is exactly provide a kind of processing step simple to overcome defect that above-mentioned prior art exists, and reaction conditions is gentle, the synthetic method of the violated pigment of cold labeling of easy handling.
Object of the present invention can be achieved through the following technical solutions:
A synthetic method for the violated pigment of cold labeling, the method be with stable isotope D or 13c mark bromobenzene, through ammonification, sulfonation synthesizing stable isotope D or 13the intermediate Sodium sulfanilate of C mark, or be raw material with bromobenzene, with stable isotope 15the aminating agent of N mark is through ammonification, sulfonation synthesizing stable isotropic substance 15the intermediate Sodium sulfanilate of N mark, then through diazotization, coupling, namely synthesis obtain stable isotope D or 15n or 13the violated pigment of C mark.
A synthetic method for the violated pigment of cold labeling, the method specifically comprises the following steps:
(1) aminating reaction: by stable isotope D or 13the bromobenzene of C mark mixes with aminating agent or with bromobenzene and stable isotope 15the aminating agent mixing of N mark, then adds amination catalyst, and under 30-150 DEG C of condition, reaction 1-20h, namely obtained stable isotope D or 15n or 13the aniline of C mark;
(2) sulfonation reaction: by stable isotope D or 15n or 13the aniline of C mark joins in organic solvent, then adds sulfonated reagent, and under 30-200 DEG C of condition, reaction 1-24h, namely obtained stable isotope D or 15n or 13the intermediate Sodium sulfanilate of C mark;
(3) diazotization reaction: by stable isotope D or 15n or 13the intermediate Sodium sulfanilate of C mark joins in acid solvent, then adds nitrite, and under 0-15 DEG C of condition, reaction 0.5-5h, namely obtained containing stable isotope D or 15n or 13c marks the diazo liquid of Sodium sulfanilate diazonium salt;
(4) coupled reaction: add beta naphthal in the diazo liquid of step (3), and under-30-100 DEG C of condition, reaction 0.5-8h, namely obtained stable isotope D or 15n or 13the violated pigment Acid Orange II of C mark.
Described stable isotope D or 15n or 13the molecular structural formula of the violated pigment Acid Orange II of C mark is:
Wherein, * represents that this place's carbon atom is 13c atom.
Described aminating agent is one or more in ammoniacal liquor, liquefied ammonia, sodium amide or potassium amide, described amination catalyst is one or more in iron trichloride, cupric chloride, cupric oxide, ferric oxide, ferric sulfate, copper sulfate, described sulfonated reagent is one or more in oleum, sulfuric acid or sulphur trioxide, described organic solvent is one or more in methyl alcohol, ethanol, ether, acetonitrile, diacetyl oxide, ethylene glycol, orthodichlorobenzene, and described acid solvent is one or more in sulfuric acid, acetic acid, nitric acid, formic acid, hydrochloric acid.
Preferably, described organic solvent is one or more in methyl alcohol, ethanol, ethylene glycol or orthodichlorobenzene.
Described bromobenzene and the mol ratio of aminating agent are 1:1-40, preferred 1:1-15, described aniline and the mol ratio of sulfonated reagent are 1:1-6, preferred 1:2-4, described intermediate sulfanilate and the mol ratio of nitrite are 1:1-6, preferred 1:1-3, in described diazo liquid, the mol ratio of Sodium sulfanilate diazonium salt and beta naphthal is 1:1-6, preferred 1:1-4.
A synthetic method for the violated pigment of cold labeling, the method specifically comprises the following steps:
(A) aminating reaction: by stable isotope D or 13the bromobenzene of C mark mixes with aminating agent or with bromobenzene and stable isotope 15the aminating agent mixing of N mark, then adds amination catalyst, and under 30-150 DEG C of condition, reaction 1-20h, namely obtained stable isotope D or 15n or 13the aniline of C mark;
(B) sulfonation reaction: by stable isotope D or 15n or 13the aniline of C mark joins in organic solvent, then adds sulfonated reagent, and under 30-200 DEG C of condition, reaction 1-24h, namely obtained stable isotope D or 15n or 13the intermediate Sodium sulfanilate of C mark;
(C) diazotization reaction: by stable isotope D or 15n or 13the intermediate Sodium sulfanilate of C mark joins in acid solvent, then adds nitrite, and under 0-15 DEG C of condition, reaction 0.5-5h, namely obtained containing stable isotope D or 15n or 13c marks the diazo liquid of Sodium sulfanilate diazonium salt;
(D) coupled reaction: add diacetyl succinic acid dimethyl ester in the diazo liquid of step (C), adjust ph to 5, under 90-150 DEG C of condition, reaction 2-4h, obtained midbody solution, more separately get the diazo liquid of a step (C), and be added dropwise in midbody solution, under 0 DEG C of condition, reaction 4-5h, namely obtained stable isotope D or 15n or 13the violated pigment lemon yellow of C mark.
Described stable isotope D or 13c or 15the molecular structural formula of the violated pigment lemon yellow of N mark is:
Wherein, * represents that this place's carbon atom is 13C atom.
Described aminating agent is one or more in ammoniacal liquor, liquefied ammonia, sodium amide or potassium amide, described amination catalyst is one or more in iron trichloride, cupric chloride, cupric oxide, ferric oxide, ferric sulfate, copper sulfate, described sulfonated reagent is one or more in oleum, sulfuric acid or sulphur trioxide, described organic solvent is one or more in methyl alcohol, ethanol, ether, acetonitrile, diacetyl oxide, ethylene glycol, orthodichlorobenzene, and described acid solvent is one or more in sulfuric acid, acetic acid, nitric acid, formic acid, hydrochloric acid.
Preferably, described organic solvent is one or more in methyl alcohol, ethanol, ethylene glycol or orthodichlorobenzene.
Described bromobenzene and the mol ratio of aminating agent are 1:1-40, preferred 1:1-15, described aniline and the mol ratio of sulfonated reagent are 1:1-6, preferred 1:2-4, described intermediate sulfanilate and the mol ratio of nitrite are 1:1-6, preferred 1:1-3, in described diazo liquid, the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester is 1:1-6, preferred 1:1-4.
Synthesizing stable isotope D of the present invention or 15n or 13acid Orange II and the lemon yellow of C mark can adopt following operational path to represent:
Compared with prior art, the present invention has following characteristics:
(1) synthetic method of the violated pigment Acid Orange II of a kind of cold labeling, lemon yellow is made public for the first time;
(2) operational path is simple, is easy to synthesis;
(3) the easily separated purification of product, product chemical purity is more than 99.0%, and isotopic abundance, more than 98.0%, fully can meet the demand of field of food safety trace detection;
(4) there is good economy and use value, can be used for industrial production of magnifying, there is good promotion prospect.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in detail.
Embodiment 1
A, cold labeling aniline-D 5synthesis
Bromobenzene-D is added successively in flask 5, ammoniacal liquor, bromobenzene-D 5be 1:10 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1) respectively, and the distilled water of reaction volume 20%, stir, be heated to 60 DEG C, reaction 18h.After reaction terminates, extraction, washing, dry.Thick yield is 68.5%, distillation, and yield 42.0%, HPLC detects purity 99.4%, abundance 99.2%.
The synthesis of B, cold labeling Sodium sulfanilate
Aniline-the D of cold labeling is added in flask 5, then add oleum successively, aniline-D 5be 1:2 with the mol ratio of oleum, then add ethylene glycol, aniline-D 5be 1:10 with the mol ratio of ethylene glycol.Reaction vacuum seal, temperature of reaction controls at 120 DEG C, reaction 4h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 85.5%, recrystallization, yield 80.0%.HPLC detects purity 99.2%, abundance 99.0%.
The synthesis of C, cold labeling Acid Orange II
The Sodium sulfanilate that stable isotope D marks is added in flask, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.2:4, react 20min at 0 DEG C after, slowly with the mol ratio of Sodium sulfanilate diazonium salt and beta naphthal for 1:1.1, add beta naphthal, react 1h, add sodium-chlor with volume ratio 10%, suction filtration, drying, to weigh.Yield is 78.2%, recrystallization, and yield is that 65.2%, HPLC detects purity 99.0%, abundance 98.8%.
Embodiment 2
A, cold labeling aniline-D 5synthesis
Bromobenzene-D is added successively in flask 5, ammoniacal liquor, bromobenzene-D 5be 1:15 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1) respectively, and reaction volume 20% distilled water, stir, be heated to 60 DEG C, reaction 18h.After reaction terminates, extraction, washing, dry.Thick yield is 68.5%, distillation, and yield 42.0%, HPLC detects purity 99.3%, abundance 99.1%.
The synthesis of B, cold labeling Sodium sulfanilate
Aniline-the D of cold labeling is added in flask 5, then add oleum successively, aniline-D 5be 1:2.5 with the mol ratio of oleum, then add orthodichlorobenzene, aniline-D 5be 1:8 with the mol ratio of orthodichlorobenzene.Reaction vacuum seal, temperature of reaction controls at 140 DEG C, reaction 5h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 87.5%, recrystallization, yield 82.3%.HPLC detects purity 99.4%, abundance 99.0%.
The synthesis of C, cold labeling Acid Orange II
The Sodium sulfanilate that stable isotope D marks is added in flask, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.5:3, react 30min at 0 DEG C after, slowly with the mol ratio of Sodium sulfanilate diazonium salt and beta naphthal for 1:1.2, add beta naphthal, react 2h, add sodium-chlor with volume ratio 10%, suction filtration, drying, to weigh.Yield is 79.2%, recrystallization, and yield is that 66.2%, HPLC detects purity 99.0%, abundance 98.9%.
Embodiment 3
A, cold labeling aniline- 13c 6synthesis
Add successively in flask bromobenzene- 13c 6, ammoniacal liquor, bromobenzene- 13c 6be 1:15 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1.5) respectively, and reaction volume 20% distilled water, stir, be heated to 100 DEG C, reaction 20h.After reaction terminates, extraction, washing, dry.Thick yield is 70.5%, distillation, and yield 46.0%, HPLC detects purity 99.4%, abundance 99.5%.
B, cold labeling Sodium sulfanilate- 13c 6synthesis
Add in flask the aniline of cold labeling- 13c 6, then add oleum successively, aniline- 13c 6be 1:3 with the mol ratio of oleum, then add ethylene glycol, aniline- 13c 6be 1:12 with the mol ratio of ethylene glycol.Reaction vacuum seal, temperature of reaction controls at 160 DEG C, reaction 4h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 84.5%, recrystallization, yield 81.0%.HPLC detects purity 99.0%, abundance 99.3%.
C, cold labeling Acid Orange II- 13c 6synthesis
Stable isotope is added in flask 13the Sodium sulfanilate of C mark, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:2:3.5, react 30min at 0 DEG C after, slowly with the mol ratio of Sodium sulfanilate diazonium salt and beta naphthal for 1:1.3, add beta naphthal, react 2h, add sodium-chlor with volume ratio 10%, suction filtration, drying, to weigh.Yield is 79.2%, recrystallization, and yield is that 68.2%, HPLC detects purity 99.0%, abundance 99.0%.
Embodiment 4
A, cold labeling aniline- 13c 6synthesis
Add successively in flask bromobenzene- 13c 6, ammoniacal liquor, bromobenzene- 13c 6be 1:15 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1.5) respectively, and reaction volume 20% distilled water, stir, be heated to 70 DEG C, reaction 24h.After reaction terminates, extraction, washing, dry.Thick yield is 77.5%, distillation, and yield 53.0%, HPLC detects purity 98.8%, abundance 99.7%.
B, cold labeling Sodium sulfanilate- 13c 6synthesis
Add in flask the aniline of cold labeling- 13c 6, then add oleum successively, aniline- 13c 6be 1:2.5 with the mol ratio of oleum, then add orthodichlorobenzene, aniline- 13c 6be 1:14 with the mol ratio of orthodichlorobenzene.Reaction vacuum seal, temperature of reaction controls at 165 DEG C, reaction 4.5h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 84.5%, recrystallization, yield 78.8%.HPLC detects purity 98.6%, abundance 99.5%.
C, cold labeling Acid Orange II- 13c 6synthesis
Stable isotope is added in flask 13the Sodium sulfanilate of C mark, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.6:3.5, react 40min at 0 DEG C after, slowly with the mol ratio of Sodium sulfanilate diazonium salt and beta naphthal for 1:1.2, add beta naphthal, react 3h, add sodium-chlor with volume ratio 10%, suction filtration, drying, to weigh.Yield is 76.2%, recrystallization, and yield is that 65.2%, HPLC detects purity 98.5%, abundance 99.2%.
Embodiment 5
A, cold labeling aniline- 15the synthesis of N
Add successively in flask bromobenzene, 15n-ammoniacal liquor, bromobenzene with 15the mol ratio of N-ammoniacal liquor is 1:6, adds iron trichloride and ferric oxide (both mol ratios are 1:1.5) respectively, and reaction volume 20% distilled water, stirs, is heated to 85 DEG C, reaction 20h.After reaction terminates, extraction, washing, dry.Thick yield is 60.5%, distillation, and yield 40.3%, HPLC detects purity 99.2%, abundance 99.5%.
B, cold labeling Sodium sulfanilate- 15the synthesis of N
Add in flask the aniline of cold labeling- 15n, then add oleum successively, aniline- 15the mol ratio of N and oleum is 1:4, then adds ethylene glycol, aniline- 15the mol ratio of N and ethylene glycol is 1:10.Reaction vacuum seal, temperature of reaction controls at 135 DEG C, reaction 3.5h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 76.5%, recrystallization, yield 72.0%.HPLC detects purity 98.2%, abundance 99.0%.
C, cold labeling Acid Orange II- 15the synthesis of N
Stable isotope is added in flask 15the Sodium sulfanilate of N mark, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:2:5, react 35min at 0 DEG C after, slowly with the mol ratio of Sodium sulfanilate diazonium salt and beta naphthal for 1:1.1, add beta naphthal, react 3h, add sodium-chlor with volume ratio 10%, suction filtration, drying, to weigh.Yield is 76.2%, recrystallization, and yield is that 63.2%, HPLC detects purity 98.5%, abundance 98.7%.
Embodiment 6
A, cold labeling aniline- 15the synthesis of N
Add successively in flask bromobenzene, 15n-ammoniacal liquor, bromobenzene with 15the mol ratio of N-ammoniacal liquor is 1:9, adds iron trichloride and ferric oxide (both mol ratios are 1:2) respectively, and reaction volume 20% distilled water, stirs, is heated to 90 DEG C, reaction 20h.After reaction terminates, extraction, washing, dry.Thick yield is 68.5%, distillation, and yield 43.0%, HPLC detects purity 99.2%, abundance 99.2%.
B, cold labeling Sodium sulfanilate- 15the synthesis of N
Add in flask the aniline of cold labeling- 15n, then add oleum successively, aniline- 15the mol ratio of N and oleum is 1:4.5, then adds orthodichlorobenzene, aniline- 15the mol ratio of N and orthodichlorobenzene is 1:16.Reaction vacuum seal, temperature of reaction controls at 145 DEG C, reaction 4.5h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 80.5%, recrystallization, yield 78.0%.HPLC detects purity 99.0%, abundance 99.0%.
C, cold labeling Acid Orange II- 15the synthesis of N
Stable isotope is added in flask 15the Sodium sulfanilate of N mark, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.3:4.5, react 45min at 0 DEG C after, slowly with the mol ratio of Sodium sulfanilate diazonium salt and beta naphthal for 1:1.3, add beta naphthal, react 2h, add sodium-chlor with volume ratio 10%, suction filtration, drying, to weigh.Yield is 77.2%, recrystallization, and yield is that 66.2%, HPLC detects purity 98.7%, abundance 98.8%.
Embodiment 7
A, cold labeling aniline-D 5synthesis
Bromobenzene-D is added successively in flask 5, ammoniacal liquor, bromobenzene-D 5be 1:10 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1.8) respectively, and reaction volume 20% distilled water, stir, be heated to 95 DEG C, reaction 19h.After reaction terminates, extraction, washing, dry.Thick yield is 67.5%, distillation, and yield 41.5%, HPLC detects purity 99.3%, abundance 99.1%.
The synthesis of B, cold labeling Sodium sulfanilate
Aniline-the D of cold labeling is added in flask 5, then add oleum successively, aniline-D 5be 1:2.5 with the mol ratio of oleum, then add ethylene glycol, aniline-D 5be 1:14 with the mol ratio of ethylene glycol.Reaction vacuum seal, temperature of reaction controls at 120 DEG C, reaction 5h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 86.5%, recrystallization, yield 82.0%.HPLC detects purity 99.2%, abundance 98.7%.
The synthesis of C, cold labeling Acid Orange II
The Sodium sulfanilate that stable isotope D marks is added in flask, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.2:4, react 20min at 0 DEG C after, slowly with the mol ratio of Sodium sulfanilate diazonium salt and beta naphthal for 1:3, add beta naphthal, raised temperature to 90 DEG C, reaction 4h, adds sodium-chlor with volume ratio 10%, suction filtration, drying, to weigh.Yield is 68.2%, recrystallization, and yield is that 55.2%, HPLC detects purity 99.0%, abundance 98.6%.
Embodiment 8
A, cold labeling aniline-D 5synthesis
Bromobenzene-D is added successively in flask 5, ammoniacal liquor, bromobenzene-D 5be 1:13 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:2) respectively, and reaction volume 20% distilled water, stir, be heated to 60 DEG C, reaction 19h.After reaction terminates, extraction, washing, dry.Thick yield is 71.5%, distillation, and yield 45.3%, HPLC detects purity 99.2%, abundance 99.4%.
The synthesis of B, cold labeling Sodium sulfanilate
Aniline-the D of cold labeling is added in flask 5, then add oleum successively, aniline-D 5be 1:3 with the mol ratio of oleum, then add orthodichlorobenzene, aniline-D 5be 1:10 with the mol ratio of orthodichlorobenzene.Reaction vacuum seal, temperature of reaction controls at 120 DEG C, reaction 6h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 85.5%, recrystallization, yield 80.0%.HPLC detects purity 99.2%, abundance 99.2%.
The synthesis of C, cold labeling lemon yellow
The Sodium sulfanilate that stable isotope D marks is added in flask, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.4:5, reacts 40min, in addition as aforesaid method prepares a diazo liquid again at 0 DEG C, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.5, add diacetyl succinic acid dimethyl ester, regulate pH to 5, raised temperature to 100 DEG C, reaction 3h, prepares midbody solution.At 0 DEG C, first part of diazo liquid is added dropwise to midbody solution, reaction 4h, adds sodium-chlor with volume ratio 10%, leaves standstill 5h, suction filtration, drying, to weigh.Yield is 66.2%, recrystallization, and yield is that 55.2%, HPLC detects purity 99.0%, abundance 98.9%.
Embodiment 9
A, cold labeling aniline-D 5synthesis
Bromobenzene-D is added successively in flask 5, ammoniacal liquor, bromobenzene-D 5be 1:3 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1.6) respectively, and reaction volume 20% distilled water, stir, be heated to 95 DEG C, reaction 17h.After reaction terminates, extraction, washing, dry.Thick yield is 66.5%, distillation, and yield 41.0%, HPLC detects purity 99.3%, abundance 99.1%.
The synthesis of B, cold labeling Sodium sulfanilate
Aniline-the D of cold labeling is added in flask 5, then add oleum successively, aniline-D 5be 1:4.5 with the mol ratio of oleum, then add ethylene glycol, aniline-D 5be 1:10 with the mol ratio of ethylene glycol.Reaction vacuum seal, temperature of reaction controls at 165 DEG C, reaction 4.5h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 83.5%, recrystallization, yield 78.0%.HPLC detects purity 99.2%, abundance 99.0%.
The synthesis of C, cold labeling lemon yellow
Natural abundance Sodium sulfanilate is added in flask, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.5:4.5, at 0 DEG C, react 45min, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.4, add diacetyl succinic acid dimethyl ester, regulate pH to 5, raised temperature to 95 DEG C, reaction 3.5h, prepares midbody solution.In addition, as aforesaid method adds the Sodium sulfanilate of stable isotope D mark prepared by upper step, more a diazo liquid is prepared, at 0 DEG C, diazo liquid is added dropwise to midbody solution, reaction 5h, add sodium-chlor with volume ratio 10%, leave standstill 8h, suction filtration, drying, to weigh.Yield is 69.2%, recrystallization, and yield is that 58.2%, HPLC detects purity 98.6%, abundance 98.6%.
Embodiment 10
A, cold labeling aniline-D 5synthesis
Bromobenzene-D is added successively in flask 5, ammoniacal liquor, bromobenzene-D 5be 1:16 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1.8) respectively, and reaction volume 20% distilled water, stir, be heated to 60 DEG C, reaction 20h.After reaction terminates, extraction, washing, dry.Thick yield is 65.5%, distillation, and yield 41.0%, HPLC detects purity 99.3%, abundance 99.1%.
The synthesis of B, cold labeling Sodium sulfanilate
Aniline-the D of cold labeling is added in flask 5, then add sulfuric acid successively, aniline-D 5be 1:6 with the mol ratio of sulfuric acid, then add orthodichlorobenzene, aniline-D 5be 1:10 with the mol ratio of orthodichlorobenzene.Reaction vacuum seal, temperature of reaction controls at 155 DEG C, reaction 7h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 87.5%, recrystallization, yield 81.0%.HPLC detects purity 99.2%, abundance 98.9%.
The synthesis of C, cold labeling lemon yellow
Natural abundance Sodium sulfanilate is added in flask, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.5:4.5, at 0 DEG C, react 45min, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.4, add diacetyl succinic acid dimethyl ester, regulate pH to 5, raised temperature to 95 DEG C, reaction 3.5h, prepares midbody solution.In addition, as aforesaid method adds the Sodium sulfanilate of stable isotope D mark prepared by upper step, more a diazo liquid is prepared, at 0 DEG C, diazo liquid is added dropwise to midbody solution, reaction 5h, add sodium-chlor with volume ratio 10%, leave standstill 8h, suction filtration, drying, to weigh.Yield is 69.2%, recrystallization, and yield is that 58.2%, HPLC detects purity 98.9%, abundance 98.7%.
Embodiment 11
A, cold labeling aniline- 13c 6synthesis
Add successively in flask bromobenzene- 13c 6, ammoniacal liquor, bromobenzene- 13c 6be 1:15 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:2) respectively, and reaction volume 20% distilled water, stir, be heated to 110 DEG C, reaction 23h.After reaction terminates, extraction, washing, dry.Thick yield is 76.5%, distillation, and yield 53.0%, HPLC detects purity 99.1%, abundance 99.4%.
B, cold labeling Sodium sulfanilate- 13c 6synthesis
Add in flask the aniline of cold labeling- 13c 6, then add oleum successively, aniline- 13c 6be 1:3.5 with the mol ratio of oleum, then add ethylene glycol, aniline- 13c 6be 1:15 with the mol ratio of ethylene glycol.Reaction vacuum seal, temperature of reaction controls at 130 DEG C, reaction 5h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 84.5%, recrystallization, yield 80.8%.HPLC detects purity 98.7%, abundance 99.1%.
The synthesis of C, cold labeling lemon yellow
Natural abundance Sodium sulfanilate is added in flask, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.3:5, at 0 DEG C, react 50min, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.3, add diacetyl succinic acid dimethyl ester, regulate pH to 5, raised temperature to 110 DEG C, reaction 3h, prepares midbody solution.In addition, as aforesaid method adds stable isotope prepared by upper step 13the Sodium sulfanilate of C mark, then prepares a diazo liquid, at 0 DEG C, diazo liquid is added dropwise to midbody solution, and reaction 5h, adds sodium-chlor with volume ratio 10%, leaves standstill 8h, suction filtration, drying, weighs.Yield is 72.2%, recrystallization, and yield is that 59.2%, HPLC detects purity 98.3%, abundance 98.5%.
Embodiment 12
A, cold labeling aniline- 13c 6synthesis
Add successively in flask bromobenzene- 13c 6, ammoniacal liquor, bromobenzene- 13c 6be 1:13 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1.2) respectively, and reaction volume 20% distilled water, stir, be heated to 80 DEG C, reaction 20h.After reaction terminates, extraction, washing, dry.Thick yield is 73.5%, distillation, and yield 47.0%, HPLC detects purity 99.0%, abundance 99.5%.
B, cold labeling Sodium sulfanilate- 13c 6synthesis
Add in flask the aniline of cold labeling- 13c 6, then add oleum successively, aniline- 13c 6be 1:4 with the mol ratio of oleum, then add orthodichlorobenzene, aniline- 13c 6be 1:13 with the mol ratio of orthodichlorobenzene.Reaction vacuum seal, temperature of reaction controls at 170 DEG C, reaction 2.5h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 84.5%, recrystallization, yield 80.8%.HPLC detects purity 98.3%, abundance 99.3%.
The synthesis of C, cold labeling lemon yellow
Stable isotope is added in flask 13the Sodium sulfanilate of C mark, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.5:5.5, reacts 45min, in addition at 0 DEG C, as aforesaid method prepares a diazo liquid again, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.6, add diacetyl succinic acid dimethyl ester, raised temperature to 130 DEG C, reaction 2.5h, prepares midbody solution.At 0 DEG C, first part of diazo liquid is added dropwise to midbody solution, reaction 4h, adds sodium-chlor with volume ratio 10%, leaves standstill 7h, suction filtration, drying, to weigh.Yield is 63.2%, recrystallization, and yield is that 52.2%, HPLC detects purity 99.1%, abundance 98.7%.
Embodiment 13
A, cold labeling aniline- 13c 6synthesis
Add successively in flask bromobenzene- 13c 6, ammoniacal liquor, bromobenzene- 13c 6be 1:11 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1) respectively, and reaction volume 20% distilled water, stir, be heated to 75 DEG C, reaction 22h.After reaction terminates, extraction, washing, dry.Thick yield is 75.5%, distillation, and yield 51.0%, HPLC detects purity 99.1%, abundance 99.5%.
B, cold labeling Sodium sulfanilate- 13c 6synthesis
Add in flask the aniline of cold labeling- 13c 6, then add oleum successively, aniline- 13c 6be 1:3 with the mol ratio of oleum, then add ethylene glycol, aniline- 13c 6be 1:15 with the mol ratio of ethylene glycol.Reaction vacuum seal, temperature of reaction controls at 150 DEG C, reaction 4.5h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 85.5%, recrystallization, yield 80.3%.HPLC detects purity 98.5%, abundance 99.2%.
The synthesis of C, cold labeling lemon yellow
Stable isotope is added in flask 13the Sodium sulfanilate of C mark, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.2:6, reacts 35min, in addition at 0 DEG C, as aforesaid method prepares a natural abundance diazo liquid again, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.6, add diacetyl succinic acid dimethyl ester, raised temperature to 120 DEG C, reaction 4h, prepares midbody solution.At 0 DEG C, first part of diazo liquid is added dropwise to midbody solution, reaction 4.5h, adds sodium-chlor with volume ratio 10%, leaves standstill 4h, suction filtration, drying, to weigh.Yield is 65.2%, recrystallization, and yield is that 53.2%, HPLC detects purity 98.4%, abundance 98.7%.
Embodiment 14
A, cold labeling aniline- 13c 6synthesis
Add successively in flask bromobenzene- 13c 6, ammoniacal liquor, bromobenzene- 13c 6be 1:11 with the mol ratio of ammoniacal liquor, add iron trichloride and ferric oxide (both mol ratios are 1:1.3) respectively, and reaction volume 20% distilled water, stir, be heated to 65 DEG C, reaction 25h.After reaction terminates, extraction, washing, dry.Thick yield is 71.5%, distillation, and yield 45.3%, HPLC detects purity 99.2%, abundance 99.5%.
B, cold labeling Sodium sulfanilate- 13c 6synthesis
Add in flask the aniline of cold labeling- 13c 6, then add oleum successively, aniline- 13c 6be 1:3 with the mol ratio of oleum, then add orthodichlorobenzene, aniline- 13c 6be 1:12 with the mol ratio of orthodichlorobenzene.Reaction vacuum seal, temperature of reaction controls at 120 DEG C, reaction 4h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 84.5%, recrystallization, yield 81.8%.HPLC detects purity 98.9%, abundance 99.2%.
The synthesis of C, cold labeling lemon yellow
Stable isotope is added in flask 13the Sodium sulfanilate of C mark, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.8:6, reacts 55min, in addition at 0 DEG C, as aforesaid method prepares a diazo liquid again, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.6, add diacetyl succinic acid dimethyl ester, raised temperature to 110 DEG C, reaction 4h, prepares midbody solution.At 0 DEG C, first part of diazo liquid is added dropwise to midbody solution, reaction 4.5h, adds sodium-chlor with volume ratio 10%, leaves standstill 5h, suction filtration, drying, to weigh.Yield is 68.2%, recrystallization, and yield is that 56.2%, HPLC detects purity 98.9%, abundance 98.7%.
Embodiment 15
A, cold labeling aniline- 15the synthesis of N
Add successively in flask bromobenzene, 15n-ammoniacal liquor, bromobenzene with 15the mol ratio of N-ammoniacal liquor is 1:8, adds iron trichloride and ferric oxide (both mol ratios are 1:2) respectively, and reaction volume 20% distilled water, stirs, is heated to 80 DEG C, reaction 23h.After reaction terminates, extraction, washing, dry.Thick yield is 71.5%, distillation, and yield 44.0%, HPLC detects purity 99.3%, abundance 99.4%.
B, cold labeling Sodium sulfanilate- 15the synthesis of N
Add in flask the aniline of cold labeling- 15n, then add oleum successively, aniline- 15the mol ratio of N and oleum is 1:5, then adds ethylene glycol, aniline- 15the mol ratio of N and ethylene glycol is 1:15.Reaction vacuum seal, temperature of reaction controls at 150 DEG C, reaction 4h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 85.5%, recrystallization, yield 80.2%.HPLC detects purity 99.3%, abundance 99.2%.
The synthesis of C, cold labeling lemon yellow
Natural abundance Sodium sulfanilate is added in flask, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.4:5, at 0 DEG C, react 55min, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.2, add diacetyl succinic acid dimethyl ester, regulate pH to 5, raised temperature to 130 DEG C, reaction 4h, prepares midbody solution.In addition, as aforesaid method adds stable isotope prepared by upper step 15the Sodium sulfanilate of N mark, then prepares a diazo liquid, at 0 DEG C, diazo liquid is added dropwise to midbody solution, and reaction 4h, adds sodium-chlor with volume ratio 10%, leaves standstill 5h, suction filtration, drying, weighs.Yield is 71.2%, recrystallization, and yield is that 56.2%, HPLC detects purity 98.8%, abundance 98.7%.
Embodiment 16
A, cold labeling aniline- 15the synthesis of N
Add successively in flask bromobenzene, 15n-ammoniacal liquor, bromobenzene with 15the mol ratio of N-ammoniacal liquor is 1:9, adds iron trichloride and ferric oxide (both mol ratios are 1:2) respectively, and reaction volume 20% distilled water, stirs, is heated to 85 DEG C, reaction 23h.After reaction terminates, extraction, washing, dry.Thick yield is 72.5%, distillation, and yield 43.0%, HPLC detects purity 99.2%, abundance 99.1%.
B, cold labeling Sodium sulfanilate- 15the synthesis of N
Add in flask the aniline of cold labeling- 15n, then add oleum successively, aniline- 15the mol ratio of N and oleum is 1:3.5, then adds orthodichlorobenzene, aniline- 15the mol ratio of N and orthodichlorobenzene is 1:15.Reaction vacuum seal, temperature of reaction controls at 120 DEG C, reaction 4h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 87.5%, recrystallization, yield 82.5%.HPLC detects purity 99.0%, abundance 99.0%.
The synthesis of C, cold labeling lemon yellow
Natural abundance Sodium sulfanilate is added in flask, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.1:4, at 0 DEG C, react 55min, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.3, add diacetyl succinic acid dimethyl ester, regulate pH to 5, raised temperature to 150 DEG C, reaction 4h, prepares midbody solution.In addition, as aforesaid method adds stable isotope prepared by upper step 15the Sodium sulfanilate of N mark, then prepares a diazo liquid, at 0 DEG C, diazo liquid is added dropwise to midbody solution, and reaction 4h, adds sodium-chlor with volume ratio 10%, leaves standstill 3h, suction filtration, drying, weighs.Yield is 71.2%, recrystallization, and yield is that 56.2%, HPLC detects purity 98.6%, abundance 98.4%.
Embodiment 17
A, cold labeling aniline- 15the synthesis of N
Add successively in flask bromobenzene, 15n-ammoniacal liquor, bromobenzene with 15the mol ratio of N-ammoniacal liquor is 1:7, adds iron trichloride and ferric oxide (both mol ratios are 1:3) respectively, and reaction volume 20% distilled water, stirs, is heated to 85 DEG C, reaction 21h.After reaction terminates, extraction, washing, dry.Thick yield is 71.5%, distillation, and yield 44.8%, HPLC detects purity 99.0%, abundance 99.2%.
B, cold labeling Sodium sulfanilate- 15the synthesis of N
Add in flask the aniline of cold labeling- 15n, then add oleum successively, aniline- 15the mol ratio of N and oleum is 1:4, then adds ethylene glycol, aniline- 15the mol ratio of N and ethylene glycol is 1:14.Reaction vacuum seal, temperature of reaction controls at 140 DEG C, reaction 4h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 85.5%, recrystallization, yield 81.0%.HPLC detects purity 99.2%, abundance 99.0%.
The synthesis of C, cold labeling lemon yellow
Stable isotope is added in flask 15the Sodium sulfanilate of N mark, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.1:4, reacts 40min, in addition at 0 DEG C, as aforesaid method prepares a diazo liquid again, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.4, add diacetyl succinic acid dimethyl ester, raised temperature to 110 DEG C, reaction 3h, prepares midbody solution.At 0 DEG C, first part of diazo liquid is added dropwise to midbody solution, reaction 5h, adds sodium-chlor with volume ratio 10%, leaves standstill 5h, suction filtration, drying, to weigh.Yield is 67.2%, recrystallization, and yield is that 56.2%, HPLC detects purity 99.1%, abundance 98.7%.
Embodiment 18
A, cold labeling aniline- 15the synthesis of N
Add successively in flask bromobenzene, 15n-ammoniacal liquor, bromobenzene with 15the mol ratio of N-ammoniacal liquor is 1:7, adds iron trichloride and ferric oxide (both mol ratios are 1:3) respectively, and reaction volume 20% distilled water, stirs, is heated to 80 DEG C, reaction 20h.After reaction terminates, extraction, washing, dry.Thick yield is 68.5%, distillation, and yield 43.0%, HPLC detects purity 99.4%, abundance 99.2%.
B, cold labeling Sodium sulfanilate- 15the synthesis of N
Add in flask the aniline of cold labeling- 15n, then add oleum successively, aniline- 15the mol ratio of N and oleum is 1:3, then adds ethylene glycol, aniline- 15the mol ratio of N and ethylene glycol is 1:12.Reaction vacuum seal, temperature of reaction controls at 120 DEG C, reaction 4h stopped reaction.Standing and reacting thing, question response thing cools, and adds sodium hydroxide, until in alkalescence, cooling, treats solid crystal, suction filtration.Yield is 86.5%, recrystallization, yield 82.0%.HPLC detects purity 99.2%, abundance 99.0%.
The synthesis of C, cold labeling lemon yellow
Stable isotope is added in flask 15the Sodium sulfanilate of N mark, add Sodium Nitrite, hydrochloric acid successively, the mol ratio of Sodium sulfanilate and Sodium Nitrite, hydrochloric acid is 1:1.5:2, reacts 40min, in addition at 0 DEG C, as aforesaid method prepares a diazo liquid again, slowly with the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester for 1:1.5, add diacetyl succinic acid dimethyl ester, raised temperature to 110 DEG C, reaction 3h, prepares midbody solution.At 0 DEG C, first part of diazo liquid is added dropwise to midbody solution, reaction 4h, adds sodium-chlor with volume ratio 10%, leaves standstill 5h, suction filtration, drying, to weigh.Yield is 66.2%, recrystallization, and yield is that 55.2%, HPLC detects purity 99.0%, abundance 98.8%.

Claims (9)

1. a synthetic method for the violated pigment of cold labeling, is characterized in that, the method be with stable isotope D or 13c mark bromobenzene, through ammonification, sulfonation synthesizing stable isotope D or 13the intermediate Sodium sulfanilate of C mark, or be raw material with bromobenzene, with stable isotope 15the aminating agent of N mark is through ammonification, sulfonation synthesizing stable isotropic substance 15the intermediate Sodium sulfanilate of N mark, then through diazotization, coupling, namely synthesis obtain stable isotope D or 15n or 13the violated pigment of C mark.
2. the synthetic method of the violated pigment of a kind of cold labeling according to claim 1, it is characterized in that, the method specifically comprises the following steps:
(1) aminating reaction: by stable isotope D or 13the bromobenzene of C mark mixes with aminating agent or with bromobenzene and stable isotope 15the aminating agent mixing of N mark, then adds amination catalyst, and under 30-150 DEG C of condition, reaction 1-20h, namely obtained stable isotope D or 15n or 13the aniline of C mark;
(2) sulfonation reaction: by stable isotope D or 15n or 13the aniline of C mark joins in organic solvent, then adds sulfonated reagent, and under 30-200 DEG C of condition, reaction 1-24h, namely obtained stable isotope D or 15n or 13the intermediate Sodium sulfanilate of C mark;
(3) diazotization reaction: by stable isotope D or 15n or 13the intermediate Sodium sulfanilate of C mark joins in acid solvent, then adds nitrite, and under 0-15 DEG C of condition, reaction 0.5-5h, namely obtained containing stable isotope D or 15n or 13c marks the diazo liquid of Sodium sulfanilate diazonium salt;
(4) coupled reaction: add beta naphthal in the diazo liquid of step (3), and under-30-100 DEG C of condition, reaction 0.5-8h, namely obtained stable isotope D or 15n or 13the violated pigment Acid Orange II of C mark.
3. the synthetic method of the violated pigment of a kind of cold labeling according to claim 2, is characterized in that, described stable isotope D or 15n or 13the molecular structural formula of the violated pigment Acid Orange II of C mark is:
Wherein, * represents that this place's carbon atom is 13c atom.
4. the synthetic method of the violated pigment of a kind of cold labeling according to claim 2, it is characterized in that, described aminating agent is ammoniacal liquor, liquefied ammonia, one or more in sodium amide or potassium amide, described amination catalyst is iron trichloride, cupric chloride, cupric oxide, ferric oxide, ferric sulfate, one or more in copper sulfate, described sulfonated reagent is oleum, one or more in sulfuric acid or sulphur trioxide, described organic solvent is methyl alcohol, ethanol, ether, acetonitrile, diacetyl oxide, ethylene glycol, one or more in orthodichlorobenzene, described acid solvent is sulfuric acid, acetic acid, nitric acid, formic acid, one or more in hydrochloric acid.
5. the synthetic method of the violated pigment of a kind of cold labeling according to claim 2, it is characterized in that, described bromobenzene and the mol ratio of aminating agent are 1:1-40, described aniline and the mol ratio of sulfonated reagent are 1:1-6, described intermediate sulfanilate and the mol ratio of nitrite are 1:1-6, and in described diazo liquid, the mol ratio of Sodium sulfanilate diazonium salt and beta naphthal is 1:1-6.
6. the synthetic method of the violated pigment of a kind of cold labeling according to claim 1, it is characterized in that, the method specifically comprises the following steps:
(A) aminating reaction: by stable isotope D or 13the bromobenzene of C mark mixes with aminating agent or with bromobenzene and stable isotope 15the aminating agent mixing of N mark, then adds amination catalyst, and under 30-150 DEG C of condition, reaction 1-20h, namely obtained stable isotope D or 15n or 13the aniline of C mark;
(B) sulfonation reaction: by stable isotope D or 15n or 13the aniline of C mark joins in organic solvent, then adds sulfonated reagent, and under 30-200 DEG C of condition, reaction 1-24h, namely obtained stable isotope D or 15n or 13the intermediate Sodium sulfanilate of C mark;
(C) diazotization reaction: by stable isotope D or 15n or 13the intermediate Sodium sulfanilate of C mark joins in acid solvent, then adds nitrite, and under 0-15 DEG C of condition, reaction 0.5-5h, namely obtained containing stable isotope D or 15n or 13c marks the diazo liquid of Sodium sulfanilate diazonium salt;
(D) coupled reaction: add diacetyl succinic acid dimethyl ester in the diazo liquid of step (C), adjust ph to 5, under 90-150 DEG C of condition, reaction 2-4h, obtained midbody solution, more separately get the diazo liquid of a step (C), and be added dropwise in midbody solution, under 0 DEG C of condition, reaction 4-5h, namely obtained stable isotope D or 15n or 13the violated pigment lemon yellow of C mark.
7. the synthetic method of the violated pigment of a kind of cold labeling according to claim 6, is characterized in that, described stable isotope D or 13c or 15the molecular structural formula of the violated pigment lemon yellow of N mark is:
Wherein, * represents that this place's carbon atom is 13C atom.
8. the synthetic method of the violated pigment of a kind of cold labeling according to claim 6, it is characterized in that, described aminating agent is ammoniacal liquor, liquefied ammonia, one or more in sodium amide or potassium amide, described amination catalyst is iron trichloride, cupric chloride, cupric oxide, ferric oxide, ferric sulfate, one or more in copper sulfate, described sulfonated reagent is oleum, one or more in sulfuric acid or sulphur trioxide, described organic solvent is methyl alcohol, ethanol, ether, acetonitrile, diacetyl oxide, ethylene glycol, one or more in orthodichlorobenzene, described acid solvent is sulfuric acid, acetic acid, nitric acid, formic acid, one or more in hydrochloric acid.
9. the synthetic method of the violated pigment of a kind of cold labeling according to claim 6, it is characterized in that, described bromobenzene and the mol ratio of aminating agent are 1:1-40, described aniline and the mol ratio of sulfonated reagent are 1:1-6, described intermediate Sodium sulfanilate and the mol ratio of nitrite are 1:1-6, and in described diazo liquid, the mol ratio of Sodium sulfanilate diazonium salt and diacetyl succinic acid dimethyl ester is 1:1-6.
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