CN101328319A - Water-soluble bridged ring polymethine 3H-indole cyanine dyes ultrasonic synthetic method - Google Patents
Water-soluble bridged ring polymethine 3H-indole cyanine dyes ultrasonic synthetic method Download PDFInfo
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- CN101328319A CN101328319A CNA2008100553451A CN200810055345A CN101328319A CN 101328319 A CN101328319 A CN 101328319A CN A2008100553451 A CNA2008100553451 A CN A2008100553451A CN 200810055345 A CN200810055345 A CN 200810055345A CN 101328319 A CN101328319 A CN 101328319A
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- polymethine
- cyanine dyes
- bridged ring
- indoline
- trimethylammonium
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Abstract
The invention discloses a method for ultrasonic synthesis of a serial water soluble bridge ring multi-methine 3H-indocyanine dye. Under the action of ultrasonic waves, by the one-step method or the two-step method, an intermediate of 1-1,2 or 1,3 or 1,4-carboxyl benzyl-2, 3, 3-trimethyl-3H-indolinyl-5-sulfonic kalium undergoes the condensation reaction with the intermediate or another intermediate and corresponding condensing agents such as square acid, croconic acid or isophorone, etc. to be synthesized to prepare the serial water soluble bridge ring multi-methine 3H-indocyanine dye. The method of the invention has the advantages of reducing coking side products generated due to the long-time reaction at a high temperature, improving the yield of dyes and making the transferring, the separation and the purification of reaction products easier and the operation more convenient, more effective, safer and faster, along with low reaction temperature and short reaction time.
Description
Technical field
The present invention relates to the synthetic chemistry and the Technology field of chemical industry new high-tech product (functional dye) and conventional dyes.
Background technology:
3H-indoles cyanine dyes has obtained important application as functional molecular in fields such as high-technology field DNA automatic sequencing, immunoassay, clinical diagnosis, solar cell, CD, photosensitive, new drug design and exploitations.
Chinese patent disclose the water-soluble 3H-indole cyanine dyes of a kind of series (patent No.: 02102927.X), wherein bridged ring 3H-indole cyanine dyes structural general formula is as follows:
Z＝O，S，Se，Te，CR
2R
3； R
2，R
3＝H，CH
3，CF
3，C
2H
5
R
1＝(CH
2)
m?CH
3，(CH
2)
mCOOH，(CH
2)
mSO
3 -，
m＝0-18
R
4，R
5，R
6，R
7＝H，F，(CH
2)
rCF
3，(CH
2)
rCN，SO
3 -，SO
3H，(CH
2)
rCH
3，
OH，O(CH
2)
rCH
3，(CH
2)
rCOOH；r＝0-4
Bridged ring structure Y difference in the bridged ring 3H-indole cyanine dyes compound molecule, its synthetic method differs greatly, roughly can reduce Type B, C type, D type and E type four big classes, what it adopted is the traditional heating synthetic method, and tangible improvement is not arranged on method and technology for many years, and the synthesis technique of its final step is as follows:
Along with science and technology development, the ultrasonic wave synthetic technology is used for the combined coefficient that organic chemical reactions can improve Chemicals as a kind of new form of energy, and can make that much to be difficult to the reaction that maybe can not carry out smooth, ultrasonic technology is superior to thermodynamics means such as traditional stirring and outer heating greatly as a kind of convenience, rapid, effective, safe modern synthetic technology.
Summary of the invention
The object of the invention is to provide a kind of ultrasonic synthetic method of water-soluble bridged ring polymethine 3 H-indole cyanine dyes, this invention does not change the structure and the whole synthesis route of bridged ring 3H-indole cyanine dyes in original water-soluble 3H-indole cyanine dyes, only to wherein improving by dyestuff intermediate and condensing agent condensation prepared dyestuff step (final step-committed step in the whole synthesis technique), promptly adopt the ultrasonic wave synthetic technology to improve the traditional heating synthetic method of original corresponding steps, thereby improve dyestuff and dyestuff intermediate synthetic chemical reaction rate, reduce the oxygenolysis of product under the high temperature and the generation of coking by product, improve the yield of product and make post-processing operation simpler and easy.
A. the general structure of dyestuff intermediate is as follows:
R＝o，m，or?p-CH
2C
6H
5COOH，C
2H
5，(CH
2)
5COOH?or?CH
3
X＝Cl，Br?or?I
B. the general structure of dye composition is as follows:
Z＝O，S，Se，Te，CR
2R
3；R
2，R
3＝H，CH
3，CF
3，C
2H
5
R
1-(CH
2)
m?CH
3，(CH
2)
mCOOH，(CH
2)
mSO
3 -，
m＝0-18
R
4，R
5，R
6，R
7＝H，F，(CH
2)
rCF
3，(CH
2)
rCN，SO
3 -，SO
3H，(CH
2)
rCH
3，
OH，O(CH
2)
rCH
3，(CH
2)
rCOOH；r＝0-4
The technical solution adopted for the present invention to solve the technical problems is: described method comprises the synthetic method of A dyestuff intermediate, synthetic three steps of purifying of separating with C of ultrasonic synthetic method of B dyestuff; A. the synthetic method of dyestuff intermediate: obtain 2,3,3-trimethylammonium-3H-indoline-5-sulfonic acid potassium salt from Sulphanilic Acid is synthetic, then its respectively and adjacent or or to chloromethyl benzoic acid, the hexabromo caproic acid, or the iodoethane reaction can obtain intermediate 1-adjacent or to carboxylic benzyl-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate, 1-carboxylic amyl group-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate, or 1-ethyl-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate; Its synthesis technique flow process is as follows:
X＝Cl，Br?or?I
B. the ultrasonic synthetic method of dyestuff is synthetic:
Promptly adopt the ultrasonic wave synthetic technology to improve original traditional heating synthetic method, (frequency is that water or organism are that lotus root is closed liquid under the effect of 10kHz～500MHz) in ultrasonic wave; Catalyzer and solvent are pyridine, quinoline, acetic anhydride, sodium-acetate and acetic anhydride mixture or pyridine, benzene or toluene and propyl carbinol mixture; Synthesis reaction temperature is 15～95 ℃, and the reaction times is 20～400min.Intermediate 1-adjacent or to carboxylic benzyl-2; 3; 3-trimethylammonium-3H-indoline-5-potassium sulfonate and any above-mentioned a kind of intermediate or 2; 3; 3-trimethylammonium-3H-indoline reaches corresponding side's acid, croconic acid, isophorone, 2-chloro-1-formyl radical-3-hydroxyl first subunit cyclopentenes, 2-chloro-1-formyl radical-3-hydroxyl first subunit tetrahydrobenzene, 2-phenoxy group-1-formyl radical-3-hydroxyl first subunit tetrahydrobenzene and 2-phenoxy group-1-formyl radical-3-hydroxyl first subunit cyclopentenes condensing agent, both can obtain having the serial bridged ring dye composition of above-mentioned general formula by single stage method or two-step approach condensation.
C. product separation and purification: the product that obtains is adopted common silicagel column, propyl carbinol, pyridine (or quinoline), ethanol and water mixture with suitable proportion, trichloromethane and methyl alcohol or propyl carbinol and vinegar stock are eluent, or RP-C18 reversed-phase column methyl alcohol is that eluent separates purification with water mixture.
The invention has the beneficial effects as follows: in original traditional synthesis method, bridged ring 3H-indole cyanine dyes synthetic except the D type be the room temperature reaction, the temperature of reaction of all the other synthetic committed steps is all higher (generally under refluxing, about more than 80 ℃ or 110 ℃), reaction times is grown (generally more than 240min, the soprano reaches 960min).Use modern ultrasonic wave synthetic technology, adopt new synthetic method synthetic, not only make temperature of reaction reduce (50～95 ℃), reaction times shortening (20～400min), and reduced Yin Gaowen and reacted and the coking by product of generation down for a long time, the dye product yield is increased, and the transfer of reaction product with separate that purifying becomes is more prone to, operate easier, safe, rapid and effective.
Embodiment
Embodiment 1
(dyestuff intermediate: 1-to carboxylic benzyl-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate)
2,3,3-trimethylammonium-3H-indoline-5-sulfonic acid potassium salt 4.0mmol and chloromethyl benzoic acid 4.8mmol mixed in orthodichlorobenzene 10ml and be heated to 105-110 ℃, behind the reaction 10h, solvent is removed in cooling, residue solid grinds with Virahol, obtains the intermediate solid particulate.
Embodiment 2
(Type B: Z=CR
2R
3R
2, R
3=CH
3R
1=CH
2C
6H
4COOH; R
4, R
6, R
7=H; R
5=SO
3K)
With 1-to carboxylic benzyl-2,3, benzene and propyl carbinol (1: 1) the 10ml solution of the 8ml pyridine solution of 3-trimethylammonium-3H-indoline-5-potassium sulfonate 1.4mmol and the sour 0.7mmol in side join respectively in the there-necked flask, react the 3h postcooling to room temperature in 70 ℃ under ultrasonic wave (ultrasonic cleaner) effect.The dilution that adds diethyl ether is left standstill.Filter, get blue solid.Silicagel column separates, and elutriant is a propyl carbinol: pyridine: ethanol: water=3-1: 1: 1: 0-0.5.
Embodiment 3
(type: Z=CR
2R
3R
2, R
3=CH
3R
1=CH
2C
6H
4COOH; R
4, R
6, R
7=H; R
5=SO
3K)
1-is to carboxylic benzyl-2,3, after the 3-trimethylammonium-3H-indoline-8ml pyridine solution of 5-potassium sulfonate 1.4mmol and the benzene of croconic acid 0.7mmol and propyl carbinol (1: 1) 10ml solution mix, under ultrasonic wave (ultrasonic cleaner) effect,, be cooled to room temperature in 70 ℃ of reaction 3h.The dilution that adds diethyl ether is left standstill.Filter, get green solid.Silicagel column separates, and elutriant is a propyl carbinol: pyridine: ethanol=3-1: 1: 1.
Embodiment 4
(D type: Z=CR
2R
3R
2, R
3=CH
3R
1=CH
2C
6H
4COOH; R
4, R
6, R
7=H; R
5=SO
3K)
1-is to carboxylic benzyl-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate 3.0mmol, and condensing agent 2.0mmol with the dissolving of 30ml acetic anhydride, adds sodium acetate, anhydrous 5.0mmol again, and nitrogen protection is reacted 4h under room temperature under ultrasonic wave (ultrasonic cleaner) effect.Add the ether dilution, leave standstill.Filter throw out dissolve with methanol, elimination insolubles, concentrating under reduced pressure.Silicagel column separates, and elutriant is a propyl carbinol: pyridine: ethanol=3-1: 1: 1 or trichloromethane: ethanol=4: 1, collect green color component.
Embodiment 5
(E type: Z=S; L=SCH
3R
1=(CH
2)
4SO
3 -R
4, R
5, R
6, R
7=H; X=CH
3C
6H
4SO
3 -)
1-is to carboxylic benzyl-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate 3.0mmol, isophorone 9.0mmol joins in the 35ml acetic anhydride,, cools off down in 95 ℃ of about 12h of reaction in ultrasonic wave (ultrasonic cleaner) effect, separate out solid after, filtration.Filter cake and N-(δ-sulphur butyl)-2-methylthio group heterocyclic quaternary ammonium salt 6.0mmol joins in the 10ml pyridine, continues under ultrasonic wave (ultrasonic cleaner) effect in 95 ℃ of reaction 1h.Be cooled to room temperature.The dilution that adds diethyl ether is left standstill.Filter dye solids.
Claims (4)
1. the ultrasonic synthetic method of a serial water-soluble bridged ring polymethine 3 H-indole cyanine dyes is characterized in that: adopt ultrasonic synthetic method synthesizing series water-soluble bridged ring polymethine 3 H-indole cyanine dyes, said method comprising the steps of:
A. dyestuff intermediate is synthetic;
B. the ultrasonic synthetic method of dyestuff is synthetic;
C. Separation ﹠ Purification;
The general structure of described serial water-soluble bridged ring polymethine 3 H-indole cyanine dyes is as follows:
Z＝O，S，Se，Te，CR
2R
3；R
2，R
3＝H，CH
3，CF
3，C
2H
5
R
1＝(CH
2)
m?CH
3，(CH
2)
mCOOH，(CH
2)
mSO
3 -，
m＝0-18
R
4，R
5，R
6，R
7＝H，F，(CH
2)
rCF
3，(CH
2)
rCN，SO
3 -，SO
3H，(CH
2)
rCH
3，OH，O(CH
2)
rCH
3，(CH
2)
rCOOH；r＝0-4。
2. the ultrasonic synthetic method of serial water-soluble bridged ring polymethine 3 H-indole cyanine dyes according to claim 1, it is characterized in that: at first, obtain 2 from the Sulphanilic Acid raw material is synthetic, 3,3-trimethylammonium-3H-indoline-5-sulfonic acid potassium salt, then 2,3,3-trimethylammonium-3H-indoline-5-sulfonic acid potassium salt respectively and adjacent or or to chloromethyl benzoic acid, the hexabromo caproic acid, or iodoethane reaction obtain intermediate 1-adjacent or to carboxylic benzyl-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate, 1-carboxylic amyl group-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate, or 1-ethyl-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate obtains the water-soluble bridged ring polymethine 3 H-indole cyanine dyes intermediate; Its synthesis technique flow process is as follows:
3. the ultrasonic synthetic method of serial water-soluble bridged ring polymethine 3 H-indole cyanine dyes according to claim 1, it is characterized in that: under the ultrasonic wave effect, intermediate 1-adjacent or to carboxylic benzyl-2,3,3-trimethylammonium-3H-indoline-5-potassium sulfonate and any above-mentioned a kind of intermediate or 2,3,3-trimethylammonium-3H-indoline and the acid of corresponding side, croconic acid, isophorone, 2-chloro-1-formyl radical-3-hydroxyl first subunit cyclopentenes, 2-chloro-1-formyl radical-3-hydroxyl first subunit tetrahydrobenzene, 2-phenoxy group-1-formyl radical-3-hydroxyl first subunit tetrahydrobenzene and 2-phenoxy group-1-formyl radical-3-hydroxyl first subunit cyclopentenes condensing agent obtains having the serial water-soluble bridged ring polymethine 3 H-indole cyanine dyes compound of above-mentioned general formula by single stage method or two-step approach condensation; Its synthesis technique flow process is as follows:
4. the ultrasonic synthetic method of serial water-soluble bridged ring polymethine 3 H-indole cyanine dyes according to claim 3, it is characterized in that: ultrasonic frequency is 10kHz～500MHz, water or organism are that lotus root is closed liquid; Catalyzer and solvent are pyridine, quinoline, acetic anhydride, sodium-acetate and acetic anhydride mixture or pyridine, benzene or toluene and propyl carbinol mixture; Synthesis reaction temperature is 15～95 ℃, and the reaction times is 20～400min.
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|---|---|---|---|
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|---|---|---|---|
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| CN101328319B CN101328319B (en) | 2013-06-05 |
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| CN1159385C (en) * | 2002-01-30 | 2004-07-28 | 大连理工大学 | Water soluble 3H-indolyl cyanine dye |
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- 2008-07-02 CN CN 200810055345 patent/CN101328319B/en not_active Expired - Fee Related
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| CN102952413A (en) * | 2012-09-21 | 2013-03-06 | 深圳市美凯特科技有限公司 | Benzpyrole squaric acid cyanine dye and preparation method thereof |
| CN103030989A (en) * | 2012-12-10 | 2013-04-10 | 北京化工大学 | Synthesis method of water-soluble squarylium indocyanine multifunctional cell fluorescent dye |
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| CN103275514B (en) * | 2013-05-28 | 2014-06-18 | 常州大学 | Chemical sensor for identifying Fe ions based on indol-croconium dye and preparation method for same |
| CN105219120A (en) * | 2014-06-25 | 2016-01-06 | 华东理工大学 | A kind of indolenium squaraine cyanine dye and preparation method thereof |
| CN104448891A (en) * | 2014-10-31 | 2015-03-25 | 山东师范大学 | Near-infrared fluorescent dye with large stokes shift and synthesis method and application |
| CN104557804A (en) * | 2014-12-31 | 2015-04-29 | 宏业生化股份有限公司 | Method for synthesizing furfuralcohol through ultrasonic-assisted catalysis of furfural and device realizing method |
| CN105238093A (en) * | 2015-09-02 | 2016-01-13 | 北京化工大学 | Amphiphilic indole squarylium cyanine dye and application thereof in long-acting marking of lysosome |
| CN105801465A (en) * | 2016-04-11 | 2016-07-27 | 常州大学 | Water-soluble indole croconium cyanine colorimetric probe, preparation method and application |
| CN108559300A (en) * | 2018-04-11 | 2018-09-21 | 燕山大学 | A kind of preparation of side's acid cyanines copper ion probe and detection method |
| CN108559300B (en) * | 2018-04-11 | 2020-01-07 | 燕山大学 | Preparation and detection method of squarylium cyanine copper ion probe |
| WO2020181931A1 (en) * | 2019-03-08 | 2020-09-17 | 中国科学院宁波工业技术研究院慈溪生物医学工程研究所 | Heptamethine carboxylindole cyanine dye and preparation method and application therefor |
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