CN108675989B - Fe3+Molecular fluorescence test agent and preparation method thereof - Google Patents
Fe3+Molecular fluorescence test agent and preparation method thereof Download PDFInfo
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- CN108675989B CN108675989B CN201810380960.3A CN201810380960A CN108675989B CN 108675989 B CN108675989 B CN 108675989B CN 201810380960 A CN201810380960 A CN 201810380960A CN 108675989 B CN108675989 B CN 108675989B
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- 238000006555 catalytic reaction Methods 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- QSWDMMVNRMROPK-UHFFFAOYSA-K chromium(3+) trichloride Chemical compound [Cl-].[Cl-].[Cl-].[Cr+3] QSWDMMVNRMROPK-UHFFFAOYSA-K 0.000 description 1
- 239000011636 chromium(III) chloride Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001967 indiganyl group Chemical group [H][In]([H])[*] 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 229910052603 melanterite Inorganic materials 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 150000005172 methylbenzenes Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 230000008557 oxygen metabolism Effects 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- RDRCCJPEJDWSRJ-UHFFFAOYSA-N pyridine;1h-pyrrole Chemical compound C=1C=CNC=1.C1=CC=NC=C1 RDRCCJPEJDWSRJ-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 229940043267 rhodamine b Drugs 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 235000021547 stock Nutrition 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- GJBRNHKUVLOCEB-UHFFFAOYSA-N tert-butyl benzenecarboperoxoate Chemical compound CC(C)(C)OOC(=O)C1=CC=CC=C1 GJBRNHKUVLOCEB-UHFFFAOYSA-N 0.000 description 1
- LYDRKKWPKKEMNZ-UHFFFAOYSA-N tert-butyl benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1 LYDRKKWPKKEMNZ-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
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- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N2021/6432—Quenching
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- Chemical & Material Sciences (AREA)
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- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
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- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides Fe3+Molecular fluorescence test agent and preparation method thereof.The Fe3+Molecular fluorescence test agent has structure shown in Formulas I.Fe provided by the invention3+Molecular fluorescence test agent, for fluorophor, makes it have good photostability, excitation and transmitting light are wavelength visible, and Stokes shift is big, and quantum yield is high with 1,8- naphthalene Asia amide.Meanwhile the Fe3+In molecular fluorescence test agentGroup is for Fe3+Sensitivity it is higher, pyridine nuclear nitrogen and 4- bit amino nitrogen can be with Fe3+Complexing occurs and forms ion complexation body, so as to cause electronics transfer or energy transfer, makes the test agent in different Fe3+There is different fluorescence responses under concentration.The above reason is but also Fe provided by the invention3+Molecular fluorescence test agent has had both better test accuracy and sensitivity.
Description
Technical field
The present invention relates to organic syntheses and element analysis technology field, in particular to a kind of Fe3+Molecular fluorescence test
Agent and preparation method thereof.
Background technique
Iron is one of internal the most abundant microelement, it is the important of composition hemoglobin, myoglobins and a variety of enzymes
Ingredient takes part in the processes such as oxygen intake, oxygen metabolism, electronics transfer.If lacking iron in vivo, the synthesis of hemoglobin can be influenced,
Can make the activity of the enzymes such as cytochrome c, ribonucleotide reductase, succinate dehydrogenase reduces, so as to cause serious body
Dysfunction.Fe in human body3+The change of content is related to many diseases, as iron deficiency will lead to anaemia, cancer, diabetes and organ
Dysfunction etc., and Fe supply then can by Fenton's reaction generate Cells Induced by Reactive Oxygen Species Alzheimer's disease, Huntington's disease and
Parkinson's disease etc..Therefore, the content of iron ion in environment and human body is quick and precisely detected for the strong of Environmental security and the mankind
Health has a very important significance.
Currently, detection micro Fe3+Analytical technology there are many kinds of, including atomic absorption spectrography (AAS), plasma emissioning light
Spectrum, plasma mass, electrochemical process, titration etc..These methods are needed mostly using expensive large-scale instrument, and operation is multiple
It is miscellaneous, portability difference and unsuitable on line real-time monitoring.The equipment as needed for fluorescence analysis is simple, and have fast response time,
High sensitivity, it is easy to operate the advantages that, therefore using fluorescence probe come qualitative and quantitative detect Fe3+Have become research hotspot.
In recent years, about Fe3+The existing a small amount of report of the research of fluorescence probe.Wherein most is using rhodamine as fluorescent base
The iron ion fluorescence probe of group, such as Chinese patent CN107011351A, CN 105884788A, Synthesis and
evaluation of a novel rhodamine B-based'off-on'fluorescent chemosensor for
the selective determination of Fe3+Ions, Sensors and Actuators B:Chemicals,
2017,242,921-931.The testing principle of rhodamine fluorescence probe are as follows: by causing acyl in itself with Action of Metal Ions
Open loop occurs for amine Spirocyclic structure, and so as to cause ultravioletvisible absorption and fluorescence spectrum to change, it is different to be finally reached detection
The purpose of concentration of metal ions.
However, since rhodamine can participate in ion coupling reaction, excitation wavelength and launch wavelength can because detection from
Son variation and change, cause the rhodamine base fluorescent optical sensor of a variety of different ions that cannot use the same excitation and launch wavelength
It is detected.And the Fe of above-mentioned report3+Fluorescent optical sensor excitation wave is about 560nm, and transmitted wave is about 580nm, stoke
This (Stockes) displacement only has 20nm or so, and ordinary optical light splitting eyeglass is difficult to an exciting light and fluorescence distinguishes, thus
Influence testing result, the general light spectrum detecting apparatus high using spectral resolution carries out fluorescence signal acquisition, detection difficulty and at
This can be greatly increased.
Based on the above reasons, Fe is carried out using a kind of fluorophor that Stokes shift is bigger3+Molecular fluorescence sensor
Design be very it is necessary to.
Summary of the invention
The main purpose of the present invention is to provide a kind of Fe3+Molecular fluorescence test agent and preparation method thereof, it is existing to solve
Fe in technology3+The too small problem of molecular fluorescence test agent Stokes shift.
To achieve the goals above, according to an aspect of the invention, there is provided a kind of Fe3+Molecular fluorescence test agent,
With structure shown in Formulas I:
According to another aspect of the present invention, a kind of Fe is additionally provided3+The preparation method of molecular fluorescence test agent comprising with
Lower step:
Compound A and compound B is carried out condensation reaction, forms compound C by step S1；Compound A, compound B and change
The structure for closing object C is as follows, and wherein the X in compound A is halogen:
Compound C is hydrolyzed reaction and obtains Fe by step S23+Molecular fluorescence test agent:
Further, before step S1, preparation method further includes the steps that prepare compound A comprising: by 4- cyano
Benzoic acid and the tert-butyl alcohol carry out esterification, obtain the 4- cyanobenzoic acid tert-butyl ester；By the 4- cyanobenzoic acid tert-butyl ester, catalyst
And methanol is mixed to form mixed system, and hydrogen is passed through into mixed system and carries out hydrogenation, obtains 4- aminomethyl benzoic acid
Tert-butyl ester E；Wherein catalyst is one of Raney nickel, palladium-carbon catalyst and Co catalysts or a variety of；By 4- amino methyl
T-butyl perbenzoate E is reacted with compound F, obtains compound A；Wherein 4- aminomethyl benzoic acid tert-butyl ester E, compound
F has the following structure:
Wherein the X in compound F is halogen.
Further, step S1 includes: to mix compound A, compound B and acid binding agent with the first solvent, obtains first
Mixture；First mixture is subjected to condensation reaction at a temperature of 80~100 DEG C, obtains the first product system；By the first product
System is cooled and poured into water, and precipitating, as compound C is obtained by filtration；Preferably, the first solvent be N-Methyl pyrrolidone,
One of N, N- dimethyl acetamide, dimethyl sulfoxide, dimethyl acetamide and tetrahydrofuran are a variety of；Preferably, acid is tied up
Agent is N, one of N- diisopropylethylamine, N,N-dimethylformamide, 4-dimethylaminopyridine and triethylamine or a variety of；
Preferably, the molar ratio between compound A, compound B and acid binding agent is 1~6:1~5:1~15.
Further, after filtration step, step S1 further includes the steps that washing precipitating, washing step packet
It includes: precipitating is dissolved in chloroform, water is added thereto and is washed, liquid separation obtains organic phase and water phase；Using anhydrous
Sodium sulphate dries organic phase, filters and evaporates, obtains compound C.
Further, step S2 includes: that compound C, carbonyl removing reagent and the second solvent are mixed and reacted, and obtains the
Two product systems；It uses volume ratio to dilute the second product system for the chloroform of 1:1/methanol mixed solution, then evaporates molten
Agent obtains Fe3+Molecular fluorescence test agent；Preferably, carbonyl removing reagent be trifluoroacetic acid, the hydrochloric acid that volume ratio is 1:2 and second
Acetoacetic ester mix reagent or silica gel；Preferably, the second solvent is methylene chloride and/or chloroform；Preferably, mole of compound C
Number is that carbonyl removes the 1.8~2.0% of reagent molal quantity, preferably 1.9%.
Further, the step of 4- cyanobenzoic acid and the tert-butyl alcohol being subjected to esterification include: by 4- cyanobenzoic acid,
The 4th solvent of acylating reagent is mixed and is reacted, and obtains intermediary；After removing the solvent in intermediary, by it with esterification catalyst,
The tert-butyl alcohol is mixed and is reacted, and obtains the 4th product system；The 4th product system is purified, the 4- cyanobenzoic acid tert-butyl ester is obtained；It is excellent
Selection of land, acylating reagent are one of oxalyl chloride, thionyl chloride, phosphorus trichloride and phosphorus pentachloride or a variety of；Preferably, esterification is urged
Agent is one of pyridine, N,N-dimethylformamide, 4-dimethylaminopyridine and triethylamine or a variety of；Preferably, 4- cyanogen
Molar ratio between yl benzoic acid and acylating reagent is 2~3:3~5；Volume ratio between esterification catalyst and the tert-butyl alcohol is 1~
1.1:1。
Further, in the step of preparing 4- aminomethyl benzoic acid tert-butyl ester E, the 4- cyanobenzoic acid tert-butyl ester and catalysis
Weight ratio between agent is 10~20:1~3；Weight ratio between the 4- cyanobenzoic acid tert-butyl ester and methanol is 1~3:8~20；
Preferably, after being passed through hydrogen, the pressure of reaction system is 0.8~1.2MPa.
Further, the step of 4- aminomethyl benzoic acid tert-butyl ester E being reacted with compound F includes: by 4- ammonia
Ylmethyl t-butyl perbenzoate E, compound F are mixed and are reacted with the 5th solvent, obtain the 5th product system；Filter the 5th product
Obtained precipitating is dried system, obtains compound A；Preferably, the 5th solvent is ethyl alcohol, methanol, propyl alcohol and isopropanol
One of or it is a variety of；Preferably, the molar ratio between 4- aminomethyl benzoic acid tert-butyl ester E and compound F is 1:1.
Fe provided by the invention3+Molecular fluorescence test agent, for fluorophor, is made it have good with 1,8- naphthalene Asia amide
Photostability, excites (449nm) and transmitting light (533nm) is wavelength visible, and Stokes shift is big (84nm), quantum
Yield is high.Meanwhile the Fe3+In molecular fluorescence test agentGroup (test group) is for Fe3+Sensitivity it is higher,
Its pyridine nuclear nitrogen and 4- bit amino nitrogen can be with Fe3+Complexing occurs and forms ion complexation body, turns so as to cause electronics
Shifting or energy transfer, make the test agent in different Fe3+There is different fluorescence responses under concentration.The above reason is but also this hair
The Fe of bright offer3+Molecular fluorescence test agent has had both better test accuracy and sensitivity.
Detailed description of the invention
The accompanying drawings constituting a part of this application is used to provide further understanding of the present invention, and of the invention shows
Examples and descriptions thereof are used to explain the present invention for meaning property, does not constitute improper limitations of the present invention.In the accompanying drawings:
Fig. 1 shows the tert-butyl -4- amine picoline -1,8- naphthalimide that the embodiment of the present invention 1 is prepared
The hydrogen nuclear magnetic resonance spectrogram of ylmethyl；
Fig. 2 shows the 4- amine picoline -1,8- naphthalimido methylbenzenes that the embodiment of the present invention 1 is prepared
The hydrogen nuclear magnetic resonance spectrogram of formic acid；
Fig. 3 shows Fe obtained in the embodiment of the present invention 13+Fluorometric investigation liquid is with Fe3+Prepare liquid volume increases fluorescence
The variation diagram of spectrum；
Fig. 4 shows Fe obtained in the embodiment of the present invention 13+Fluorometric investigation liquid is with Fe3+Concentration increases fluorescence intensity
Variation diagram；
Fig. 5 shows Fe obtained in the embodiment of the present invention 13+Fluorometric investigation liquid is to Fe3+Fluorescence selectivity identify signal
Figure；
Fig. 6 shows Fe made from the embodiment of the present invention 13+Fluorometric investigation liquid detects Fe3+Anti-interference identify signal
Figure；
Specific embodiment
It should be noted that in the absence of conflict, the features in the embodiments and the embodiments of the present application can phase
Mutually combination.The present invention will be described in detail below with reference to the accompanying drawings and embodiments.
The application is described in further detail below in conjunction with specific embodiment, these embodiments should not be understood as limitation originally
Apply for range claimed.
As described in background technology part, Fe in the prior art3+Molecular fluorescence test agent Stokes shift mistake
It is small.
To solve the above-mentioned problems, the present invention provides a kind of Fe3+Molecular fluorescence test agent, with structure shown in Formulas I:
Fe provided by the invention3+Molecular fluorescence test agent, for fluorophor, is made it have good with 1,8- naphthalene Asia amide
Photostability, excites (449nm) and transmitting light (533nm) is wavelength visible, and Stokes shift is big (84nm), quantum
Yield is high.Meanwhile the Fe3+In molecular fluorescence test agentGroup (test group) is for Fe3+Sensitivity it is higher,
Its pyridine nuclear nitrogen and 4- bit amino nitrogen can be with Fe3+Complexing occurs and forms ion complexation body, turns so as to cause electronics
Shifting or energy transfer, make the test agent in different Fe3+There is different fluorescence responses under concentration.The above reason is but also this hair
The Fe of bright offer3+Molecular fluorescence test agent has had both better test accuracy and sensitivity.
According to another aspect of the present invention, a kind of Fe is additionally provided3+The preparation method of molecular fluorescence test agent comprising with
Lower step:
Compound A and compound B is carried out condensation reaction, forms compound C by step S1；Compound A, compound B and change
The structure for closing object C is as follows, and wherein the X in compound A is halogen:
Compound C is hydrolyzed reaction and obtains Fe by step S23+Molecular fluorescence test agent:
As it was noted above, the present invention restructures the Fe of Preparation Method preparation3+It is quasi- that molecular fluorescence test agent has had both better test
True property and sensitivity.And condensation reaction prepare compound C is first carried out with compound A and compound B in the preparation method, then to change
It closes object C hydrolysis and Fe is prepared3+Molecular fluorescence test agent, the reaction route is simple, and cost is relatively low, and process conditions are mild, fits
Close industrialization large-scale production.
Above compound A can select commercial product, in a preferred embodiment, before step S1, the system
Preparation Method further includes the steps that prepare compound A comprising: 4- cyanobenzoic acid and the tert-butyl alcohol are subjected to esterification, obtained
The 4- cyanobenzoic acid tert-butyl ester；By the 4- cyanobenzoic acid tert-butyl ester, catalyst (Raney nickel, palladium-carbon catalyst and Co catalysts
One of or it is a variety of) and methanol be mixed to form mixed system, be passed through into mixed system hydrogen carry out hydrogenation, obtain 4-
Aminomethyl benzoic acid tert-butyl ester E；4- aminomethyl benzoic acid tert-butyl ester E is reacted with compound F, obtains compound A；
Wherein 4- aminomethyl benzoic acid tert-butyl ester E, compound F have the following structure:
Wherein the X in compound F is halogen.
Using above method prepare compound A, route is brief, simple process, cost is lower, yield is relatively high.
Concrete technology condition in above each synthesis step can be adjusted, specific as follows:
In a preferred embodiment, above-mentioned steps S1 includes: by compound A, compound B and acid binding agent and first
Solvent mixing, obtains the first mixture；By the first mixture at 80~100 DEG C, more preferably carry out being condensed at a temperature of 90 DEG C anti-
It answers, obtains the first product system；First product system is cooled and poured into water, precipitating, as compound C is obtained by filtration.
Preferably, the first solvent includes but is not limited to N-Methyl pyrrolidone, n,N-dimethylacetamide, dimethyl Asia
One of sulfone, dimethyl acetamide and tetrahydrofuran are a variety of.
Preferably, above-mentioned acid binding agent is N-Methyl pyrrolidone, n,N-dimethylacetamide, dimethyl sulfoxide, dimethyl
One of acetamide and tetrahydrofuran are a variety of.Using these types of acid binding agent, be conducive to further increase compound A and chemical combination
Reaction efficiency between object B improves reaction conversion ratio.
Preferably, the molar ratio between compound A, compound B and acid binding agent is 1~6:1~5:1~15；Preferably, exist
After filtration step, step S1 further includes the steps that washing precipitating, and washing step includes: that precipitating is dissolved in three chloromethanes
In alkane, water is added thereto and is washed, liquid separation obtains organic phase and water phase；Using the dry organic phase of anhydrous sodium sulfate, filtering
And evaporate, obtain compound C.
It is exemplified below: by the chloro- 1,8- naphthalimide ylmethyl (compound A) of tert-butyl -4-, 2- amine first
Yl pyridines (compound B) and n,N-diisopropylethylamine are suspended in N-Methyl pyrrolidone (NMP) and 18 small in 90 DEG C of heating
When.Mixture is cooled and poured into water.Precipitating is obtained by filtration, is then dissolved in CHCl3In and be washed with water, liquid separation.Organic layer
Use Na2SO4It dries, filters and evaporates, obtain crude product, 55~60 DEG C of hot methanol hot beating of crude product filters and with 0
~10 DEG C of cold methanol washing.50~55 DEG C of hot CHCl of obtained solid (solid after cold methanol washing)3Recrystallization, obtains
Yellow crystal tert-butyl -4- amine picoline -1,8- naphthalimide ylmethyl (compound C).
In a preferred embodiment, above-mentioned steps S2 includes: that compound C, carbonyl removing reagent and second is molten
Agent is mixed and is reacted, and obtains the second product system；Use volume ratio for the chloroform of 1:1/methanol mixed solution dilution second
Then product system evaporates solvent, obtain Fe3+Molecular fluorescence test agent.Using the tertiary fourth of carbonyl removing reagent elimination reaction object C
Oxygen carbonyl (BOC) group.Volume ratio is used to can be used as solvent cut back for chloroform/methanol mixed solution of 1:1, from
And remove excessive carbonyl removing reagent.
Preferably, above-mentioned carbonyl removing reagent is trifluoroacetic acid, the hydrochloric acid that volume ratio is 1:2 and ethyl acetate mixing try
Agent or silica gel.For reducing side reaction and simplifying the purpose of aftertreatment technology, more preferably removed using trifluoroacetic acid as carbonyl
Reagent.Preferably, the second solvent is methylene chloride and/or chloroform, wherein smaller, more environmentally friendly using methylene chloride toxicity.It is preferred that
Ground, the molal quantity of compound C are that carbonyl removes the 1.8~2.0% of reagent molal quantity, more preferably 1.9%.
It is exemplified below: trifluoroacetic acid (TFA) is added to tert-butyl -4- amine picoline -1,8- naphthalimide base
CH where methyl benzoic acid ester (compound C)2Cl2In solution.Acquired solution is stirred at room temperature about 1 hour, until thin layer color
Spectrum detection (TLC) shows that most of tert-butyl -4- amine picoline -1,8- naphthalimido methyl benzoic acid ester disappears.
Then by the mixture CHCl of volume ratio 1:13: MeOH dilutes and evaporates solvent.Repeat 4 to 8 times to remove TFA, then
Being placed in pump is completely dried it in upper 30 minutes, obtains yellow crystal 4- amine picoline -1,8-naphthalimide ylmethyl benzene
Formic acid (Fe3+Molecular fluorescence test agent).
In a preferred embodiment, include: by 4- cyanobenzoic acid and the step of tert-butyl alcohol progress esterification
4- cyanobenzoic acid, acylating reagent and the 4th solvent are mixed and reacted, intermediary is obtained；After removing the solvent in intermediary,
It is mixed and reacted with esterification catalyst, t-butanol mixture, the 4th product system is obtained；The 4th product system is purified, is obtained
To the 4- cyanobenzoic acid tert-butyl ester.Acylation reaction first is carried out with 4- cyanobenzoic acid using acylating reagent and forms intermediate product, so
It can react to form the 4- cyanobenzoic acid tert-butyl ester with the tert-butyl alcohol under the action of esterification catalyst afterwards.Compared to acid with it is pure straight
It is reversed to answer, the 4- cyanobenzoic acid tert-butyl ester is prepared using the route provided by the invention, feed stock conversion is higher.Preferably, acyl
Change reagent is one of oxalyl chloride, thionyl chloride, phosphorus trichloride and phosphorus pentachloride or a variety of；Preferably, esterification catalyst is
Pyridine, N, one of N- dimethylformamide (DMF), 4-dimethylaminopyridine (DMAP) and triethylamine or a variety of.
Preferably, the molar ratio between 4- cyanobenzoic acid and acylating reagent is 2~3:3~5, more preferable 2:3；It will esterification
The total weight of catalyst and the tert-butyl alcohol is denoted as n, the weight for removing the intermediary of solvent is denoted as m, m:n is 1~3:10~20, more
Preferably 3:20；Volume ratio between esterification catalyst and the tert-butyl alcohol is 1~1.1:1, preferably 1:1.
It is exemplified below: 4- cyanobenzoic acid is dissolved in anhydrous CH2Cl2In, oxalyl chloride and dimethylformamide (DMF) is added.
Gained mixture is stirred at room temperature 1 hour, until stopping generating gas.Remove solvent, gained residue pyridine/tertiary fourth
Alcohol mixture is handled and is stirred at room temperature 6 hours.Solvent is evaporated under reduced pressure, and green residue is suspended in water, then uses
Ethyl acetate extraction.Na is used after combined organic layer is washed2SO4It dries and evaporates.Crude product passes through ethyl acetate/petroleum ether
After column purification, the white solid 4- cyanobenzoic acid tert-butyl ester is obtained.
In a preferred embodiment, in the step of preparing 4- aminomethyl benzoic acid tert-butyl ester E, 4- cyano benzene first
Weight ratio between tert-butyl acrylate and catalyst is 10~20:1~3, more preferably 10:1；The 4- cyanobenzoic acid tert-butyl ester and first
Weight ratio between alcohol is 1~3:8~20, more preferably 3:20；Preferably, after being passed through hydrogen, the pressure of reaction system is 0.8
~1.2MPa, more preferable 1MPa.Using above-mentioned technique prepare 4- aminomethyl benzoic acid tert-butyl ester E, reaction it is more efficient, on
One of Raney nickel, palladium-carbon catalyst and Co catalysts or a variety of can specifically be used by stating catalyst.
It is exemplified below: the 4- cyanobenzoic acid tert-butyl ester and Raney nickel is mixed in methyl alcohol, the hydrogen under the pressure of 1MPa
Change 16 hours.Then solvent is removed under reduced pressure in Filtration of catalyst, obtain the white solid 4- aminomethyl benzoic acid tert-butyl ester.
In a preferred embodiment, step 4- aminomethyl benzoic acid tert-butyl ester E reacted with compound F
Suddenly include: that 4- aminomethyl benzoic acid tert-butyl ester E, compound F are mixed and reacted with the 5th solvent, obtain the 5th product body
System；The 5th product system is filtered, obtained precipitating is dried, obtains compound A.
Preferably, the 5th solvent is one of ethyl alcohol, methanol, propyl alcohol and isopropanol or a variety of；Preferably, 4- amino first
Molar ratio between yl benzoic acid tert-butyl ester E and compound F is 1:1.
It is exemplified below: the chloro- 1,8- naphthalic anhydride of 4- and the 4- aminomethyl benzoic acid tert-butyl ester is put into ethyl alcohol and is formed
Suspension.It is stirred at room temperature 16 hours.The precipitating being obtained by filtration, it is 8 hours dry at 50 DEG C, obtain white powder tert-butyl-
The chloro- 1,8- naphthalimide ylmethyl of 4-.
According to another aspect of the present invention, a kind of Fe is additionally provided3+Molecular fluorescence test fluid comprising above-mentioned Fe3+Point
Sub- fluorometric investigation agent and for dissolving Fe3+The solvent of molecular fluorescence test agent；Preferred solvent is ethyl alcohol, acetonitrile, dimethyl sulfoxide
And one of N, N- dimethylformamide or a variety of, and Fe3+Fe in molecular fluorescence test fluid3+Molecular fluorescence test agent it is dense
Degree is 1~10 μm of ol/L.Based on the Fe3+The excellent performance of molecular fluorescence test agent, so that above-mentioned Fe3+Molecular fluorescence test fluid
Also good measurement sensitivity and accuracy have been had both.
Beneficial effects of the present invention are further illustrated by the following examples:
Embodiment 1
The synthesis of compound 1
4- cyanobenzoic acid (80g, 544mmol) is dissolved in anhydrous CH2Cl2In (1000mL).Addition oxalyl chloride (104mL,
816mmol) and dimethylformamide (DMF) 10mL.Resulting reaction mixture is stirred at room temperature 1 hour, until stopping
Generate gas.Remove solvent.Gained residue is handled with 600mL pyridine/t-butanol mixture (1:1) and is stirred at room temperature 6
Hour.Solvent is evaporated under reduced pressure, and green residue is suspended in H2In O.Aqueous suspension is extracted with ethyl acetate (3 × 500mL)
It takes.By combined organic layer 10%KHSO4(2 × 500mL), H2O(500mL)NaHCO3(500mL), H2O (500mL) and salt
Water (500mL) washing.By solvent Na2SO4It dries and evaporates.Crude product by using ethyl acetate/petroleum ether (1:4) column
Chromatography purifying, obtains white solid 58g (yield 52%).
The synthesis of compound 2
The mixing in methanol (500mL) by the 4- cyanobenzoic acid tert-butyl ester (58g, 37mol) and Raney nickel (5.8g), in
It is hydrogenated 16 hours under the pressure of 10kg.Then solvent is removed under reduced pressure in Filtration of catalyst, obtain white solid 47g (yield
80%).
The synthesis of compound 3
By the chloro- 1,8- naphthalic anhydride of 46.4g (200mmol) 4- and 41.4g (200mmol) 4- aminomethyl benzoic acid uncle
Butyl ester, which is put into 250mLEtOH, forms suspension.It is stirred 16 hours at RT.The precipitating being obtained by filtration is small in 50 DEG C of dryings 8
When, obtain white powder 48g (yield 57%).
The synthesis of compound 4
By 24.33g (225mmol) 2- amine picoline and the chloro- 1,8- naphthalene diformazan of 31.3g (74.3mmol) tert-butyl -4-
Imide methyl benzoic acid ester and 13mL (74.6mmol) n,N-diisopropylethylamine are suspended in 110mLN- methyl pyrrolidone
(NMP) and at 90 DEG C it heats 18 hours.Mixture is cooled and poured into water (2L).Precipitating is obtained by filtration, is then dissolved in
CHCl3It is washed in (800mL) and with water (5 × 800mL).Organic layer Na2SO4It dries, filters and evaporates, it is thick to obtain 63.55g
Product.Residue is ground with hot methanol (600mL), filters and is washed with cold methanol (600mL).The hot CHCl of obtained solid3
Recrystallization, obtains yellow crystal 32.0g (yield 87%), tert-butyl -4- amine picoline -1,8-naphthalimide ylmethyl
Benzoic ether, hydrogen nuclear magnetic resonance spectrogram are as shown in Figure 1.
The synthesis of compound 5
87.5mL (1.14mol) trifluoroacetic acid (TFA) is added to 10.68g (21.64mmol) tert-butyl -4- amine methyl
Pyridine -1,8- naphthalimide ylmethyl is in CH2Cl2In the solution of (160mL).Acquired solution is stirred in room temperature
It mixes about 1 hour, until thin-layer chromatography detection (TLC) shows most of tert-butyl -4- amine picoline -1,8- naphthalene diformazan imide
Ylmethyl disappears.Then by the CHCl of mixture 1:13: MeOH (1.2L) dilutes and evaporates solvent.Repeat 6
Secondary to remove TFA, being subsequently placed in pump is completely dried it in upper 30 minutes, obtains yellow crystal 9.35g (yield 99%), 4- amine
Picoline -1,8- naphthalimido methyl benzoic acid, hydrogen nuclear magnetic resonance spectrogram are as shown in Figure 2.
Fe3+The production of molecular fluorescence test fluid
4- amine picoline -1,8- naphthalimido methyl benzoic acid (compound 5) 0.0022g is weighed in 100ml
5 × 10 are obtained in solution (volume ratio water: ethyl alcohol: acetonitrile=1:9:10)-2The Fe of mol/L3+Molecular fluorescence tests stock solution.
Fe3+The fluorescence property of molecular fluorescence test fluid is tested
(1)Fe3+Fluorometric investigation liquid is to various concentration Fe3+Spectral signature
0.1622g iron chloride is dissolved in the Tris-HCl buffer of 0.05mol/LpH 6.0, it is fixed with 100mL volumetric flask
Hold and is made 1.0 × 10-2The Fe of mol/L3+Solution to be measured.Draw 300 μ LFe3+Fluorometric investigation liquid is added to equipped with 2700 μ l
In the fluorescence cuvette of 0.05mol/L Tris-HCl (pH6.0) buffer, it can obtain 5 μm of ol/L's after being beaten uniformly with pipette tips suction
Fe3+Fluorometric investigation liquid.It is 700V in the voltage of photomultiplier tube, excitation wavelength and launch wavelength are 449nm and 533nm respectively
Under the conditions of with fluorescence spectrophotometer measurement its in above-mentioned a series of different volumes (0 μ l, 30 μ l, 60 μ l, 90 μ l, 120 μ l, 150
μ l, 180 μ l, 210 μ l, 240 μ l, 270 μ l and 300 μ l) Fe3+The variation of transmitting photocathode in prepare liquid.Fig. 3 is this
Invent Fe obtained3+Fluorometric investigation liquid is with Fe3+The variation diagram of prepare liquid volume increase fluorescence spectrum, it can be seen that Fe3+Fluorescence
Reagent is in Fe3+In the presence of show strong fluorescent quenching.With Fe3+The increase of additional amount, the sensor exist
Fluorescence intensity at 533nm gradually decreases.Fig. 4 is Fe produced by the present invention3+Fluorometric investigation liquid is with Fe3+Concentration increases fluorescence
The variation diagram of intensity can see from the figure and work as Fe3+When concentration is within the scope of 99 μm of ol/L-909 μm of ol/L, fluorescence intensity
With Fe3+Concentration is in good linear relationship, and the linear equation of fitting can be to Fe3+Carry out quantitative detection.
(2)Fe3+Spectral signature of the fluorometric investigation liquid to other heavy metal ion
By 16 metal ion species salt [NaCl, KCl, CH3COOLi·2H2O、Al(NO3)3、CaCl2、MgCl2·6H2O、
ZnCl2、 FeSO4·7H2O、CoCl2·6H2O、MnCl2·4H2O、CrCl3·6H2O、BaCl2·2H2O、NiCl2·6H2O、
CuCl2·2H2O、CdCl2·2.5H2O、HgCl2] be accurately configured to respectively with the Tris-HCl buffer of 0.05mol/L pH 6.0
The stock solution for being 10mmol/L from concentration.Simultaneously also configure each metal ion respectively with Fe3+The titer coexisted, so that every kind
Single metal ion and Fe in titer3+Concentration be 10mmol/L.Fluorescence selectivity is tested as shown in fig. 6, concentration is equal
For the Na of 10mmol/L+、 K+、Li+、Al3+、Ca2+、Mg2+、Zn2+、Fe2+、Co2+、Mn2+、Cr3+、Ba2+、Ni2+、Cu2+、Cd2+、
Hg2+And Fe3+Ion titer takes 150 μ l to be added equipped with 5 μm of ol/L Fe respectively3+In the fluorescence cuvette of fluorescent reagent 3ml,
After fluorescent stabilization, (voltage of photomultiplier tube is for the excitation light detection for being 449nm with wavelength its variation for emitting photocathode
650V).Fig. 5 is observed it is found that Fe3+Fluorometric investigation liquid is to Fe3+There is apparent response effect, and fluorescence intensity drops at 533nm
As low as minimum, this illustrates the fluorescent reagent to Fe3+There is good selectivity.Cr is added3+Afterwards, the fluorescence intensity of sensor
It slightly reduces, but other equivalent metal ions do not influence the reagent fluorescent emission intensity substantially.In order to further study it
His common metal cation is to Fe3+The interference effect of measurement, We conducted competitive assays, i.e., will be (dense containing other ions
Degree is 10mmol/L) 10mmol/LFe3+Solution takes 150ul to be added to containing 5 μm of ol/L Fe3+The ratio of fluorescent reagent 3ml
(result is as shown in Fig. 6 white histogram) is measured in color ware.By competitive assay it is found that in addition to Cr3+, other ions and
Fe3+Fluorescent emission intensity when coexisting at 533nm is without significant changes.Therefore, in addition to Cr3+, other common metals sun
Ion and anion (different metal cation is added in the form of chloride, nitrate, sulfate or acetate) will not be done
The Fe disturbed3+Measurement.And work as Cr3+Concentration when being reduced to 50 μm of ol/L, to 500 μm of ol/L Fe3+Detection no longer cause to do
It disturbs.Therefore, this test fluid is feasible for practical application.
Embodiment 2
The technique of each step the difference is that only with embodiment 1 in the embodiment: in the synthesis process of compound 1, adjust
The dosage of whole oxalyl chloride, makes the molar ratio 2:3 of 4- cyanobenzoic acid and oxalyl chloride, and the volume ratio between pyridine and the tert-butyl alcohol is
1.1:1.The yield of final compound 1 is 49%.
Embodiment 3
The technique of each step the difference is that only with embodiment 1 in the embodiment: in the synthesis process of compound 1, adjust
The dosage of whole oxalyl chloride makes the molar ratio 3:5 of 4- cyanobenzoic acid and oxalyl chloride.The yield of final compound 1 is 53%.
Embodiment 4
The technique of each step the difference is that only with embodiment 1 in the embodiment:, will in the synthesis process of compound 1
Oxalyl chloride replaces with thionyl chloride, and adjusts its dosage and make the molar ratio 3:2 of 4- cyanobenzoic acid and thionyl chloride,.By pyrrole
Pyridine replaces with 4-dimethylaminopyridine, and adjusts its dosage and make volume ratio between 4-dimethylaminopyridine and the tert-butyl alcohol
1.2:1 the yield of final compound 1 is 45%.
Embodiment 5
The technique of each step the difference is that only with embodiment 1 in the embodiment: in the synthesis process of compound 2, adjust
The dosage of whole catalyst makes the weight ratio 20:3 between the 4- cyanobenzoic acid tert-butyl ester and Raney nickel, adjusts the use of methanol
Amount, makes the weight ratio 1:8 between the 4- cyanobenzoic acid tert-butyl ester and methanol.The yield of compound 2 is 82%.
Embodiment 6
The technique of each step the difference is that only with embodiment 1 in the embodiment: in the synthesis process of compound 2, adjust
The dosage of whole catalyst makes the weight ratio 20:3 between the 4- cyanobenzoic acid tert-butyl ester and Raney nickel, adjusts the use of methanol
Amount, makes the weight ratio 3:20 between the 4- cyanobenzoic acid tert-butyl ester and methanol.The yield of compound 2 is 84%.
Embodiment 7
The technique of each step the difference is that only with embodiment 1 in the embodiment:, will in the synthesis process of compound 2
Raney nickel replaces with palladium-carbon catalyst, and adjusts the dosage of catalyst, makes the 4- cyanobenzoic acid tert-butyl ester and palladium-carbon catalyst
Between weight ratio be 15:1, adjust the dosage of methanol, make the weight ratio 1 between the 4- cyanobenzoic acid tert-butyl ester and methanol:
6.The yield of compound 2 is 74%.
Embodiment 8
The technique of each step the difference is that only with embodiment 1 in the embodiment: in the synthesis process of compound 4, adjust
The dosage of whole 2- amine picoline and n,N-diisopropylethylamine makes the chloro- 1,8-naphthalimide ylmethyl of tert-butyl -4-
Molar ratio between benzoic ether, 2- amine picoline and n,N-diisopropylethylamine is 1:1:1.The yield of compound 4 is
85%.
Embodiment 9
The technique of each step the difference is that only with embodiment 1 in the embodiment: in the synthesis process of compound 4, adjust
The dosage of whole 2- amine picoline and n,N-diisopropylethylamine makes the chloro- 1,8-naphthalimide ylmethyl of tert-butyl -4-
Molar ratio between benzoic ether, 2- amine picoline and n,N-diisopropylethylamine is 6:5:15.The yield of compound 4 is
82%.
Embodiment 10
The technique of each step the difference is that only with embodiment 1 in the embodiment:, will in the synthesis process of compound 4
N,N-diisopropylethylamine replaces with triethylamine, and adjusts the dosage of 2- amine picoline and triethylamine, keeps tert-butyl -4- chloro-
Molar ratio between 1,8- naphthalimide ylmethyl, 2- amine picoline and triethylamine is 8:5:5.Compound
4 yield is 73%.
Embodiment 11
The technique of each step the difference is that only with embodiment 1 in the embodiment: in the synthesis process of compound 5, adjust
The dosage of whole trifluoroacetic acid makes tert-butyl -4- amine picoline -1,8-naphthalimide ylmethyl molal quantity
It is the 1.8% of trifluoroacetic acid molal quantity.The yield of compound 5 is 97%.
Embodiment 12
The technique of each step the difference is that only with embodiment 1 in the embodiment: in the synthesis process of compound 5, adjust
The dosage of whole trifluoroacetic acid makes tert-butyl -4- amine picoline -1,8-naphthalimide ylmethyl molal quantity
It is the 2.0% of trifluoroacetic acid molal quantity.The yield of compound 5 is 98%.
Embodiment 13
The technique of each step the difference is that only with embodiment 1 in the embodiment:, will in the synthesis process of compound 5
Trifluoroacetic acid replaces with volume ratio and is the hydrochloric acid and ethyl acetate mix reagent of 1:2, and adjusts its dosage, tert-butyl -4- amine first
The molal quantity of yl pyridines -1,8- naphthalimide ylmethyl is the 3.0% of the mix reagent molal quantity.Chemical combination
The yield of object 5 is 75%.
As can be seen from the above embodiments, Fe provided by the invention3+Molecular fluorescence test agent Fe in measurement sample3+When concentration
Have many advantages, such as that measurement efficiency height, high sensitivity, accuracy are good.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this field
For art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, made any to repair
Change, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Claims (15)
1. a kind of Fe3+Molecular fluorescence test agent, which is characterized in that the Fe3+Molecular fluorescence test agent has structure shown in Formulas I:
2. a kind of Fe described in claim 13+The preparation method of molecular fluorescence test agent, which is characterized in that the preparation method
The following steps are included:
Compound A and compound B is carried out condensation reaction, forms compound C by step S1；The compound A, the compound B
And the structure of the compound C is as follows, wherein the X in the compound A is halogen:
The compound C is hydrolyzed reaction and obtains the Fe by step S23+Molecular fluorescence test agent:
3. preparation method according to claim 2, which is characterized in that before the step S1, the preparation method is also
Include the steps that preparing the compound A comprising:
4- cyanobenzoic acid and the tert-butyl alcohol are subjected to esterification, obtain the 4- cyanobenzoic acid tert-butyl ester；
The 4- cyanobenzoic acid tert-butyl ester, catalyst and methanol are mixed to form mixed system, led in Xiang Suoshu mixed system
Enter hydrogen and carry out hydrogenation, obtains 4- aminomethyl benzoic acid tert-butyl ester E；Wherein the catalyst is Raney nickel, palladium carbon
One of catalyst and Co catalysts are a variety of；
The 4- aminomethyl benzoic acid tert-butyl ester E is reacted with compound F, obtains the compound A；The wherein 4-
Aminomethyl benzoic acid tert-butyl ester E, the compound F have the following structure:
Wherein the X in the compound F is halogen.
4. preparation method according to claim 2 or 3, which is characterized in that the step S1 includes:
The compound A, the compound B and acid binding agent are mixed with the first solvent, obtain the first mixture；
First mixture is subjected to the condensation reaction at a temperature of 80~100 DEG C, obtains the first product system；
First product system is cooled and poured into water, precipitating is obtained by filtration, the as described compound C.
5. the preparation method according to claim 4, which is characterized in that
First solvent is one in N-Methyl pyrrolidone, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide and tetrahydrofuran
Kind is a variety of；
The acid binding agent is N, in N- diisopropylethylamine, N,N-dimethylformamide, 4-dimethylaminopyridine and triethylamine
It is one or more；
Molar ratio between the compound A, the compound B and the acid binding agent is 1~6:1~5:1~15.
6. the preparation method according to claim 4, which is characterized in that after filtration step, the step S1 further includes
The step of washing to the precipitating, the washing step include:
The precipitating is dissolved in chloroform, water is added thereto and is washed, liquid separation obtains organic phase and water phase；
Using the dry organic phase of anhydrous sodium sulfate, filters and evaporate, obtain the compound C.
7. preparation method according to claim 2 or 3, which is characterized in that the step S2 includes:
The compound C, carbonyl removing reagent and the second solvent are mixed and reacted, the second product system is obtained；
It uses volume ratio to dilute second product system for the chloroform of 1:1/methanol mixed solution, then evaporates solvent,
Obtain the Fe3+Molecular fluorescence test agent.
8. preparation method according to claim 7, which is characterized in that
Carbonyl removing reagent is trifluoroacetic acid, the hydrochloric acid that volume ratio is 1:2 and ethyl acetate mix reagent or silica gel；
Second solvent is methylene chloride and/or chloroform；
The molal quantity of the compound C is that the carbonyl removes the 1.8~2.0% of reagent molal quantity.
9. preparation method according to claim 8, which is characterized in that
The molal quantity of the compound C is that the carbonyl removes the 1.9% of reagent molal quantity.
10. preparation method according to claim 3, which is characterized in that by the 4- cyanobenzoic acid and the tert-butyl alcohol
Carry out esterification the step of include:
The 4- cyanobenzoic acid, acylating reagent, the 4th solvent are mixed and reacted, intermediary is obtained；
After removing the solvent in the intermediary, it is mixed and reacted with esterification catalyst, the tert-butyl alcohol, the 4th product body is obtained
System；
The 4th product system is purified, the 4- cyanobenzoic acid tert-butyl ester is obtained.
11. preparation method according to claim 10, which is characterized in that the step S1 includes:
The acylating reagent is one of oxalyl chloride, thionyl chloride, phosphorus trichloride and phosphorus pentachloride or a variety of；
The esterification catalyst is one of pyridine, N,N-dimethylformamide, 4-dimethylaminopyridine and triethylamine or more
Kind；
Molar ratio between the 4- cyanobenzoic acid and the acylating reagent is 2~3:3~5；The esterification catalyst and institute
Stating the volume ratio between the tert-butyl alcohol is 1~1.1:1.
12. the preparation method according to claim 3 or 10, which is characterized in that prepare the 4- aminomethyl benzoic acid uncle
In the step of butyl ester E, the weight ratio between the 4- cyanobenzoic acid tert-butyl ester and the catalyst is 10~20:1~3；Institute
Stating the weight ratio between the 4- cyanobenzoic acid tert-butyl ester and the methanol is 1~3:8~20.
13. preparation method according to claim 12, which is characterized in that after being passed through the hydrogen, the pressure of reaction system
For 0.8~1.2MPa.
14. the preparation method according to claim 3 or 10, which is characterized in that by the tertiary fourth of 4- aminomethyl benzoic acid
The step of ester E is reacted with the compound F include:
The 4- aminomethyl benzoic acid tert-butyl ester E, the compound F are mixed and reacted with the 5th solvent, the 5th production is obtained
Objects system；
The 5th product system is filtered, obtained precipitating is dried, obtains the compound A.
15. preparation method according to claim 14, which is characterized in that
5th solvent is one of ethyl alcohol, methanol, propyl alcohol and isopropanol or a variety of；
Molar ratio between the 4- aminomethyl benzoic acid tert-butyl ester E and the compound F is 1:1.
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