CN101328319B - 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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- CN101328319B CN101328319B CN 200810055345 CN200810055345A CN101328319B CN 101328319 B CN101328319 B CN 101328319B CN 200810055345 CN200810055345 CN 200810055345 CN 200810055345 A CN200810055345 A CN 200810055345A CN 101328319 B CN101328319 B CN 101328319B
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- polymethine
- cyanine dyes
- bridged ring
- indoline
- trimethylammonium
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- LSOJDPLNESOWTI-KGVSQERTSA-N CCC(CC/C1=C\C)=C1Oc1ccccc1 Chemical compound CCC(CC/C1=C\C)=C1Oc1ccccc1 LSOJDPLNESOWTI-KGVSQERTSA-N 0.000 description 1
- UDCYBPZCSWNDET-QLKAYGNNSA-N CCC(CCC/C1=C\C)=C1Oc1ccccc1 Chemical compound CCC(CCC/C1=C\C)=C1Oc1ccccc1 UDCYBPZCSWNDET-QLKAYGNNSA-N 0.000 description 1
- 0 CCC(CCC1)=C(C)C1=CCCCC(C*1)=C(C)C1=CC Chemical compound CCC(CCC1)=C(C)C1=CCCCC(C*1)=C(C)C1=CC 0.000 description 1
- GPSDUZXPYCFOSQ-UHFFFAOYSA-N Cc1cccc(C(O)=O)c1 Chemical compound Cc1cccc(C(O)=O)c1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 1
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- Indole Compounds (AREA)
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 synthetic chemistry and the Technology field of chemical hi 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 developments.
Chinese patent disclose a kind of serial Water soluble 3 H-indolyl cyanine dye (patent No.: 02102927.X), wherein the general structure of bridged ring 3H-indole cyanine dyes compound 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
Caged scaffold Y in bridged ring 3H-indole cyanine dyes compound molecule is different, its synthetic method differs greatly, roughly can be summarized as Type B, C type, D type and the large class of E type four, what it adopted is the traditional heating synthetic method, and obvious improvement is not arranged on Method and process for many years, and the synthesis technique of its final step is as follows:
Development along with science and technology, the ultrasonic wave synthetic technology is used for as a kind of new form of energy the combined coefficient that organic chemical reactions can improve Chemicals, and can make that much to be difficult to the reaction that maybe can not carry out smooth, ultrasonic technology is superior to the thermodynamics means such as traditional stirring and external heat 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 structure and the whole synthesis route of bridged ring 3H-indole cyanine dyes in original Water soluble 3 H-indolyl cyanine dye, only improve wherein preparing dyestuff step (final step-committed step in whole synthesis technique) by dyestuff intermediate and condensing agent condensation, namely adopt the ultrasonic wave synthetic technology to improve the traditional heating synthetic method of original corresponding steps, thereby improve the synthetic chemical reaction rate of dyestuff and dyestuff intermediate, reduce the oxygenolysis of product under 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, or (CH
2)
5COOH
X=Cl, Br or I
B. the general structure of dye composition is as follows:
Z=O, S, Se, Te, or CR
2R
3R
2, R
3=H, CH
3, CF
3, or C
2H
5
R
1=(CH
2)
mCH
3, (CH
2)
mCOOH, (CH
2)
mSO
3 -, or
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, or (CH
2)
rCOOH; R=0-4
The technical solution adopted for the present invention to solve the technical problems is: described method comprises that the synthetic method of A dyestuff intermediate, the ultrasonic synthetic method of B dyestuff synthesize and three steps of C separating-purifying:
A. the synthetic method of dyestuff intermediate: from synthetic 2,3, the 3-trimethylammonium-3H-indoline-5-sulfonic acid potassium salt that obtains of Sulphanilic Acid, then its respectively and adjacent or or p-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:
B. the ultrasonic synthetic method of dyestuff is synthetic: namely adopt the ultrasonic wave synthetic technology to improve original traditional heating synthetic method, (frequency is that under the effect of 10kHz～500MHz), water or organism are that lotus root is closed liquid 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 with 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, 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 and water mixture are that eluent carries out separating-purifying.
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 room temperature reaction, the temperature of reaction of all the other synthetic committed steps is all higher (generally under refluxing, approximately 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 lower reaction for a long time and the coking by product of generation, the dye product yield is increased, and the transfer of reaction product and separating-purifying become and are more prone to, and 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 p-chloromethyl benzoic acid 4.8mmol mix in orthodichlorobenzene 10ml and are heated to 105-110 ℃, after reaction 10h, cooling, remove solvent, 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 there-necked flask, are being cooled to room temperature under ultrasonic wave (ultrasonic cleaner) effect after 70 ℃ of reaction 3h.The dilution that adds diethyl ether, standing.Filter, get blue solid.Silicagel column separates, and elutriant is 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 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, in 70 ℃ of reaction 3h, be cooled to room temperature under ultrasonic wave (ultrasonic cleaner) effect.The dilution that adds diethyl ether, standing.Filter, get green solid.Silicagel column separates, and elutriant is 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; condensing agent 2.0mmol with the dissolving of 30ml acetic anhydride, then adds sodium acetate, anhydrous 5.0mmol; nitrogen protection is reacted 4h under room temperature under ultrasonic wave (ultrasonic cleaner) effect.Add the ether dilution, standing.Filter throw out dissolve with methanol, elimination insolubles, concentrating under reduced pressure.Silicagel column separates, and elutriant is 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, and isophorone 9.0mmol joins in the 35ml acetic anhydride, and is in the about 12h of 95 ℃ of reactions, cooling under ultrasonic wave (ultrasonic cleaner) effect, after separating out solid, filters.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, standing.Filter to get 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, or CR
2R
3R
2, R
3=H, CH
3, CF
3, or C
2H
5
R
1=(CH
2)
mCH
3, (CH
2)
mCOOH, (CH
2)
mSO
3 -, or
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, or (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 p-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, obtain 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 ul-trasonic irradiation, intermediate 1-adjacent or to carboxylic benzyl-2, 3, 3-trimethylammonium-3H-indoline-5-potassium sulfonate with any above-mentioned a kind of intermediate or 2, 3, 3-trimethylammonium-3H-indoline and 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 or 2-phenoxy group-1-formyl radical-3-hydroxyl first subunit cyclopentenes condensing agent, obtain 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 that 15～95 ℃, reaction times are 20～400min.
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| CN103030989B (en) * | 2012-12-10 | 2014-05-14 | 北京化工大学 | Synthesis method of water-soluble squarylium indocyanine multifunctional cell fluorescent dye |
| 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 |
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| CN105238093B (en) * | 2015-09-02 | 2017-03-22 | 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 |
| CN108559300B (en) * | 2018-04-11 | 2020-01-07 | 燕山大学 | Preparation and detection method of squarylium cyanine copper ion probe |
| CN111662567A (en) * | 2019-03-08 | 2020-09-15 | 中国科学院宁波材料技术与工程研究所 | Heptamethine carboxyl indole cyanine dye and preparation method and application thereof |
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| CN1364829A (en) * | 2002-01-30 | 2002-08-21 | 大连理工大学 | Water soluble 3H-indolyl cyanine dye |
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| CN1364829A (en) * | 2002-01-30 | 2002-08-21 | 大连理工大学 | Water soluble 3H-indolyl cyanine dye |
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