CN102924962A - Method for preparing novel rhodamine laser dye - Google Patents
Method for preparing novel rhodamine laser dye Download PDFInfo
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- CN102924962A CN102924962A CN201210490594XA CN201210490594A CN102924962A CN 102924962 A CN102924962 A CN 102924962A CN 201210490594X A CN201210490594X A CN 201210490594XA CN 201210490594 A CN201210490594 A CN 201210490594A CN 102924962 A CN102924962 A CN 102924962A
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Abstract
The invention relates to a synthetic method for novel rhodamine laser dye. The synthetic method comprises the following steps: carrying out hydroxymethylation on an initial raw material 2,4-dinitrotoluene to obtain 2,4-dinitrobenzene ethanol, then carrying out amination to obtain 2,4-diaminobenzene ethanol, and then reacting under the action of catalyst to generate an important intermediate 6-hydroxy indoline, condensing the intermediate and acid anhydride under the action of the catalyst to obtain a novel rhodamine dye crude product, purifying the crude product by virtue of column chromatography, and finally recrystallizing to obtain a target product meeting the requirements. According to the method provided by the invention, the adopted raw materials are low in price and easy to get, operation is simple, requirement to equipment is lower, production cost is low, and the obtained novel rhodamine dye has high fluorescence intensity and stable performance and can be widely applied to the laser field.
Description
Technical field
The present invention relates to a kind of synthetic method of organic fluorescent dye, especially relate to a kind of preparation method of novel rhodamine laser dyes.
Background technology
The rhodamine compound is the alkaline xanthene dye take xanthene as parent, because special structure and corresponding fluorescent characteristic becomes the rhodamine fluorescence dye and study comparatively widely problem in chemistry and the bioanalysis field.Compare with other fluorescence dye commonly used, the rhodamine fluorescence dye has good light stability, to insensitive, the wider wavelength region of pH and the higher advantages such as fluorescence quantum yield, therefore being widely used in the aspects such as pharmacology, physiology, molecular biology, cytobiology, molecular genetics, environmental chemistry, individual molecule detection, information science, fluorescent mark, laser dyes, is the most frequently used fluorescence dye in the biological technical fields such as analytical chemistry and biomedical science.At present, the report of synthetic, the ionization of relevant rhodamine fluorescence dye and the aspects such as structure, optical characteristics and analysis is existing a lot.
But there is certain defective in rhodamine itself, such as, the fluorescent emission wavelength is short, and Stokes shift is little etc., and its application in a lot of fields is had a huge impact.This paper improves its fluorescence property for the regularity of different groups on the rhodamine compound base ring on its fluorescence property impact by introducing the different properties group at base ring, sums up the regularity that different groups change rhodamine structure fluorescence property; By to not isoplastic replacement amino on the female ring, make its maximum excitation and emission wavelength red shift, and increase fluorescence quantum yield and the fluorescence intensity of rhodamine structure, increased the stokes displacement, expanded its range of application.By ultraviolet-visible spectrum and fluorescence spectrum synthetic various Rhodamine Derivatives being carried out fluorescence property detects, sum up the relation between its constructional feature and its optical property, filter out the fluorescence dye of excellent performance, for from now on more fully the novel rhodamine fluorescent dyes of research and design reference is provided.
Summary of the invention
Purpose of the present invention is exactly to provide in order to overcome the defective that above-mentioned prior art exists that a kind of fluorescence intensity is high, the highly purified novel rhodamine of good stability, and its synthesis technique is simple, and raw material conveniently is easy to get, and is fit to the production of industrially scalable.
Purpose of the present invention can be achieved through the following technical solutions:
A kind of method for preparing novel rhodamine laser dyes is characterized in that, the method may further comprise the steps:
The preparation of (1) 2,4-dinitrobenzene ethanol: get the Paraformaldehyde 96 of 2,4-dinitrotoluene (DNT) and 1.5～2 times of molar weights, the solvent of 50～150 times of quality adds catalyzer, heats up 50～100 ℃ reaction 1～4h.Be cooled to room temperature, the underpressure distillation desolventizing obtains the thick thick product of reddish-brown, obtains brown needle-like solid behind the recrystallization.
The preparation of (2) 2,4-diamino benzene ethanols: get 2,4-dinitrobenzene ethanol, add catalyzer, the methyl alcohol of 30～80 times of quality is made solvent, is warming up to 60～110 ℃, slowly drips the hydrazine hydrate of 2～5 times of molar weights, reaction 2～6h, be cooled to room temperature, remove catalyzer, the underpressure distillation desolventizing, obtain the light gray viscous liquid, obtain the lead needle-like solid behind the recrystallization
(3) preparation of intermediate indoline: get 2, the 4-diamino benzene ethanol, the strong phosphoric acid dissolving of 10～50 times of equivalents, be warming up to 100～190 ℃, pour in the frozen water of 40～100 times of equivalents behind back flow reaction 18～30h, be neutralized to pH=3～10 with sodium hydroxide solution, brown precipitate is removed by filter, collect filtrate.With on a small quantity repeatedly extraction of ethyl acetate, organic phase to be collected, the underpressure distillation desolventizing obtains yellow oily liquid, obtains faint yellow needle-like solid behind the recrystallization.
(4) preparation of the thick product of novel rhodamine: get the intermediate 6-oxyindole quinoline that the previous step reaction obtains, the Tetra hydro Phthalic anhydride of 1～3 times of molar weight and catalyzer are heated to 120～200 ℃, react 2～8h, obtain the thick product of novel rhodamine.
(5) purification of the thick product of novel rhodamine: after thick product purified through column chromatography for separation, in anhydrous methanol, the control temperature was that 35～60 ℃ of recrystallizations obtain being the novel rhodamine of target product than crystal formation purple needle-like crystal preferably.
Solvent described in the step (1) is DMF, DMSO or THF.
Catalyzer described in the step (1) is salt of wormwood, yellow soda ash, sodium bicarbonate, sodium hydroxide or triethylamine, and { mol ratio of i Xiao Ji toluene is 1: 2-2: 3 for catalyzer and 2,4-two.
Catalyzer described in the step (2) is selected from iron(ic) chloride, zinc powder or Raney's nickel, and the mass ratio of catalyzer and 2,4-dinitrobenzene ethanol is 1: 5～1: 2.
Catalyzer described in the step (4) is sulfuric acid, nitric acid or Zinc Chloride Anhydrous, and the consumption of catalyzer is 1～5 times of intermediate consumption.
The structural formula of the carboxyl rhodamine described in the step (5) is:
Compared with prior art, the present invention has successfully prepared important indoline-like intermediate, and and then can obtain the rhodamine laser dyes of series of new, its purity is high, fluorescence property is stable, larger Stokes shift is arranged, and synthesis technique is simple, raw material conveniently is easy to get, and can accomplish the application production of industrially scalable.
Description of drawings
Fig. 1 is uv-absorbing and the fluorescence emission spectrum of the carboxyl rhodamine for preparing of embodiment 2.
Fig. 2 is synthesis route figure of the present invention.
Embodiment
The present invention is described in detail below in conjunction with the drawings and specific embodiments.
Embodiment 1
The preparation of intermediate:
Be equipped with at the same time in the 250mL there-necked flask of agitator and prolong, add successively 100mLDMF, 18.2g (100mmol) 2, the 4-dinitrotoluene (DNT), the 4.5g Paraformaldehyde 96 is warming up to 60 ℃.In 0.2h, slowly drip 20% sodium hydroxide solution 2mL, add afterreaction 2h.Be cooled to room temperature, 145 ℃ of underpressure distillation desolventizing DMF obtain the thick product of reddish-brown, and column chromatography for separation is purified and obtained thick product, and Virahol is done solvent recrystallization, obtains brown needle-like solid 17.3g, yield 83%.
Be equipped with at the same time in the 250mL there-necked flask of agitator and prolong, add successively 120mL methyl alcohol, 9g (45mmol) 6-nitroindoline quinoline, the 5g Raney's nickel, be warming up to 68 ℃ and be heated to backflow, in 0.5h, slowly drip the mixed solution of 12mL methyl alcohol and 6mL hydrazine hydrate, add rear back flow reaction 2h.Be cooled to room temperature, remove by filter the Raney's nickel in the reaction mixture, the underpressure distillation desolventizing obtains the light gray viscous liquid, and column chromatography for separation is purified and obtained 6.3g product, yield 97.5%.
In the 250mL there-necked flask of mechanical stirring, reflux condensing tube and nitrogen protection device is housed; add 6.792; 4-diamino benzene ethanol (44mmol); dissolve with 75g (85%) phosphoric acid; be warming up to 175 ℃, pour into behind the back flow reaction 24h in the 80mL frozen water, be neutralized to pH=6 with sodium hydroxide solution; brown precipitate is removed by filter, collect filtrate.With on a small quantity repeatedly extraction of ethyl acetate, organic phase to be collected, the underpressure distillation desolventizing obtains the reddish-brown oily liquids, and column chromatography for separation is purified, and obtains the higher faint yellow solid of 3.1g purity, is intermediate 6-oxyindole quinoline, yield 52%.
Synthetic route is as follows:
Embodiment 2
The preparation of novel rhodamine and purifying:
With 1g6-oxyindole quinoline, 1.125g Tetra hydro Phthalic anhydride and 1.36g Zinc Chloride Anhydrous join and are equipped with in the churned mechanically 100mL there-necked flask, and nitrogen protection, oil bath are heated to 175 ℃, and intermittently mechanical stirring is reacted 4h.After the cooling down, the reactant dissolve with methanol removes by filter insoluble impurity.The underpressure distillation desolventizing is dissolved fully with few methyl alcohol of trying one's best again, and the rear 100mL massfraction that slowly splashes into is in 1% the sodium perchlorate acidic aqueous solution, to separate out red solid.Filter, washing, vacuum-drying obtains novel rhodamine crude product 1.09g, yield 78%.
Thick product is dissolved in the hot saturated solution of formation in the methanol solution,, solution is placed 80 ℃ of water naturally cooling, until water temperature is down to about 5 ℃, obtain blue needle-like crystal 4.95g.
Embodiment 3
A kind of method for preparing novel rhodamine laser dyes, its technical process as shown in Figure 2, the method may further comprise the steps:
The preparation of 2,4-dinitrobenzene ethanol: get the Paraformaldehyde 96 of 2,4-dinitrotoluene (DNT) and 1.5 times of molar weights, the DMF of 50 times of quality makes solvent, adds catalyzer carbonic acid potassium, and the mol ratio of salt of wormwood and 2,4-dinitrotoluene (DNT) is 2: 3, is warming up to 60 ℃, reaction 2h.Be cooled to room temperature, the underpressure distillation desolventizing obtains the thick thick product of reddish-brown, obtains brown needle-like solid behind the recrystallization.
The preparation of 2,4-diamino benzene ethanol: get 2,4-dinitrobenzene ethanol, add the catalyzer Raney's nickel, the mass ratio of catalyzer and 2,4-dinitrobenzene ethanol is 1: 2, methyl alcohol with 40 times of quality is made solvent, is warming up to 60 ℃, slowly drips the hydrazine hydrate of 2 times of molar weights, reaction 2h, be cooled to room temperature, remove catalyzer, the underpressure distillation desolventizing, obtain the light gray viscous liquid, obtain the lead needle-like solid behind the recrystallization.
The preparation of intermediate indoline: get 2,4-diamino benzene ethanol, the strong phosphoric acid dissolving of 20 times of equivalents, be warming up to 120 ℃, pour into behind the back flow reaction 20h in the frozen water of 60 times of equivalents, be neutralized to pH=5 with sodium hydroxide solution, brown precipitate is removed by filter, collect filtrate.With on a small quantity repeatedly extraction of ethyl acetate, organic phase to be collected, the underpressure distillation desolventizing obtains yellow oily liquid, obtains faint yellow needle-like solid behind the recrystallization.
The preparation of the thick product of novel rhodamine: get the intermediate 6-oxyindole quinoline that the previous step reaction obtains, the Tetra hydro Phthalic anhydride of 2 times of molar weights and catalyzer zinc chloride, the consumption of catalyzer are 2 times of intermediate consumption.Be heated to 120 ℃, react 3h, obtain the thick product of carboxyl rhodamine.
The purification of the thick product of novel rhodamine: after thick product purified through column chromatography for separation, in anhydrous methanol, 40 ℃ of recrystallizations of control temperature obtained being the novel rhodamine of target product than crystal formation purple needle-like crystal preferably.
Embodiment 4
The preparation of intermediate indoline:
The preparation of 2,4-dinitrobenzene ethanol: the Paraformaldehyde 96 of getting 2,4-dinitrotoluene (DNT) and 2 times of molar weights, the THF of 100 times of quality makes solvent, adds catalyzer carbonic acid hydrogen sodium, sodium bicarbonate and 2, the mol ratio of 4-dinitrotoluene (DNT) is 2:3, is warming up to 70 ℃, reaction 4h.Be cooled to room temperature, the underpressure distillation desolventizing obtains the thick thick product of reddish-brown, obtains brown needle-like solid behind the recrystallization.
The preparation of 2,4-diamino benzene ethanol: get 2,4-dinitrobenzene ethanol, add the catalyzer Raney's nickel, the mass ratio of catalyzer and 2,4-dinitrobenzene ethanol is 1:3, methyl alcohol with 50 times of quality is made solvent, is warming up to 60 ℃, slowly drips the hydrazine hydrate of 3 times of molar weights, reaction 5h, be cooled to room temperature, remove catalyzer, the underpressure distillation desolventizing, obtain the light gray viscous liquid, obtain the lead needle-like solid behind the recrystallization.
The preparation of intermediate indoline: get 2,4-diamino benzene ethanol, the strong phosphoric acid dissolving of 30 times of equivalents, be warming up to 150 ℃, pour into behind the back flow reaction 24h in the frozen water of 60 times of equivalents, be neutralized to pH=6 with sodium hydroxide solution, brown precipitate is removed by filter, collect filtrate.With on a small quantity repeatedly extraction of ethyl acetate, organic phase to be collected, the underpressure distillation desolventizing obtains yellow oily liquid, obtains faint yellow needle-like solid behind the recrystallization, is intermediate 6-oxyindole quinoline.
Claims (6)
1. a method for preparing novel rhodamine laser dyes is characterized in that, the method may further comprise the steps:
The preparation of (1) 2,4-dinitrobenzene ethanol: get the Paraformaldehyde 96 of 2,4-dinitrotoluene (DNT) and 1.5～2 times of molar weights, the solvent of 50～150 times of quality adds catalyzer, heats up 50～100 ℃ reaction 1～4h.Be cooled to room temperature, the underpressure distillation desolventizing obtains the thick thick product of reddish-brown, obtains brown needle-like solid behind the recrystallization.
The preparation of (2) 2,4-diamino benzene ethanols: get 2,4-dinitrobenzene ethanol, add catalyzer, the methyl alcohol of 30～80 times of quality is made solvent, is warming up to 60～110 ℃, slowly drips the hydrazine hydrate of 2～5 times of molar weights, reaction 2～6h, be cooled to room temperature, remove catalyzer, the underpressure distillation desolventizing, obtain the light gray viscous liquid, obtain the lead needle-like solid behind the recrystallization.
(3) preparation of intermediate indoline: get 2, the 4-diamino benzene ethanol, the strong phosphoric acid dissolving of 10～50 times of equivalents, be warming up to 100～190 ℃, pour in the frozen water of 40～100 times of equivalents behind back flow reaction 18～30h, be neutralized to pH=3～10 with sodium hydroxide solution, brown precipitate is removed by filter, collect filtrate.With on a small quantity repeatedly extraction of ethyl acetate, organic phase to be collected, the underpressure distillation desolventizing obtains yellow oily liquid, obtains faint yellow needle-like solid behind the recrystallization.
(4) preparation of carboxyl rhodamine: get the intermediate 6-oxyindole quinoline that the previous step reaction obtains, the Tetra hydro Phthalic anhydride of 1～3 times of molar weight and catalyzer are heated to 120～200 ℃, react 2～8h, obtain the thick product of carboxyl rhodamine.
(5) preparation of the thick product of novel rhodamine: the thick product of carboxyl rhodamine that obtains is dissolved in the absolute methanol solution of 30～60 times of quality, add catalyzer, back flow reaction 12～24h, underpressure distillation desolventizing, then in water, separate out, obtain the crude product of novel rhodamine.
(6) purification of the thick product of novel rhodamine: after the purification of thick product process column chromatography for separation, in anhydrous methanol, the control temperature is that 35～60 ℃ of recrystallizations obtain preferably purple needle-like crystal of crystal formation, is the novel rhodamine of target product.
2. a kind of method for preparing novel rhodamine laser dyes according to claim 1 is characterized in that, the solvent described in the step (1) is DMF, DMSO or THF.
3. a kind of method for preparing novel rhodamine laser dyes according to claim 1, it is characterized in that, catalyzer described in the step (1) is salt of wormwood, yellow soda ash, sodium bicarbonate, sodium hydroxide or triethylamine, the mol ratio of catalyzer and 2,4-dinitrotoluene (DNT) is 1: 2～2: 3.
4. a kind of method for preparing novel rhodamine laser dyes according to claim 1 is characterized in that step
(2) catalyzer described in is selected from iron(ic) chloride, zinc powder or Raney's nickel, and the mass ratio of catalyzer and 2,4-dinitrobenzene ethanol is 1: 5～1: 2.
5. a kind of method for preparing novel rhodamine laser dyes according to claim 1 is characterized in that, the catalyzer described in the step (4) is sulfuric acid, nitric acid or Zinc Chloride Anhydrous, and the consumption of catalyzer is 1～5 times of intermediate consumption.
6. a kind of method for preparing novel rhodamine laser dyes according to claim 1 is characterized in that, the structural formula of the carboxyl rhodamine described in the step (4) is:
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113072561A (en) * | 2021-03-29 | 2021-07-06 | 华东理工大学 | Synthesis method of long-wavelength asymmetric rhodamine dye |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3413302A (en) * | 1965-05-17 | 1968-11-26 | Allied Allied Chemical Corp | Phthaloylpyrrocoline compounds |
| US3932415A (en) * | 1972-04-17 | 1976-01-13 | Eastman Kodak Company | Pyrylium dyes having a fused rigidized nitrogen-containing ring |
| JPH01168667A (en) * | 1987-12-24 | 1989-07-04 | Nippon Kayaku Co Ltd | Production of 4-hydroxyindoline |
| US5256799A (en) * | 1992-07-14 | 1993-10-26 | The United States Of Americas As Represented By The United States Department Of Energy | Preparation of 6-hydroxyindolines and their use for preparation of novel laser dyes |
| CN1911912A (en) * | 2006-08-30 | 2007-02-14 | 天津大学 | Synthesis method of indole |
| CN102337041A (en) * | 2011-07-19 | 2012-02-01 | 华东理工大学 | Method for preparing rhodamine fluorescent dyes |
| CN102634225A (en) * | 2012-03-24 | 2012-08-15 | 大连理工大学 | Method for resolving and synthetizing 5(6) substitutional rhodamine isomer |
-
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- 2012-11-27 CN CN201210490594XA patent/CN102924962A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3413302A (en) * | 1965-05-17 | 1968-11-26 | Allied Allied Chemical Corp | Phthaloylpyrrocoline compounds |
| US3932415A (en) * | 1972-04-17 | 1976-01-13 | Eastman Kodak Company | Pyrylium dyes having a fused rigidized nitrogen-containing ring |
| JPH01168667A (en) * | 1987-12-24 | 1989-07-04 | Nippon Kayaku Co Ltd | Production of 4-hydroxyindoline |
| US5256799A (en) * | 1992-07-14 | 1993-10-26 | The United States Of Americas As Represented By The United States Department Of Energy | Preparation of 6-hydroxyindolines and their use for preparation of novel laser dyes |
| CN1911912A (en) * | 2006-08-30 | 2007-02-14 | 天津大学 | Synthesis method of indole |
| CN102337041A (en) * | 2011-07-19 | 2012-02-01 | 华东理工大学 | Method for preparing rhodamine fluorescent dyes |
| CN102634225A (en) * | 2012-03-24 | 2012-08-15 | 大连理工大学 | Method for resolving and synthetizing 5(6) substitutional rhodamine isomer |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113072561A (en) * | 2021-03-29 | 2021-07-06 | 华东理工大学 | Synthesis method of long-wavelength asymmetric rhodamine dye |
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Application publication date: 20130213 |