CN104448898A

CN104448898A - Synthetic method of pyronine derivative dye

Info

Publication number: CN104448898A
Application number: CN201410723141.6A
Authority: CN
Inventors: 吴学; 周鑫; 曾义英; 柳志学; 石连生; 李彩梅
Original assignee: Yanbian University
Current assignee: Shandong Ameson Biotechnology Co., Ltd
Priority date: 2014-12-04
Filing date: 2014-12-04
Publication date: 2015-03-25
Anticipated expiration: 2034-12-04
Also published as: CN104448898B

Abstract

The invention discloses a synthetic method of a pyronine derivative dye. The synthetic method comprises the following steps: with pyronine as a raw material, producing carbine serving as an intermediate under the action of potassium tert-butoxide, carrying out reaction on carbine and sulfur or oxygen to produce pyronine thione or ketone, and then carrying out reaction on pyronine thione and amine or halohydrocarbon to produce the pyronine derivative dye. The synthetic method is safe and simple in operation, short in reaction time and good in yield and purity of the pyronine derivative dye.

Description

A kind of synthetic method of pyronin derivative dye

Technical field

The present invention relates to a kind of synthetic method of pyronin derivative dye.

Background technology

Pyronin derivative is the dyestuff that a class is excellent, and it has good stability, fluorescence quantum yield advantages of higher.When the substituted element on 9 is sulphur, dyestuff provides strong red fluorescence; When being nitrogen, provide strong green fluorescence.But the synthesis ratio of current this kind of dyestuff is more difficult, general synthetic method is that pyronin initial oxidation is become ketone, then ketone carries out nucleophilic substitution reaction with nucleophilic reagent and generates target product under the catalysis of Trifluoromethanesulfonic anhydride, this process needs experience 5 step altogether, length consuming time, productive rate is low, and in oxidation step, use a large amount of highly toxic substance potassium cyanide.Therefore, develop new synthetic technology to be necessary.

Summary of the invention

Instant invention overcomes in existing synthetic technology and use violent in toxicity potassium cyanide, long reaction time, the shortcoming that productive rate is low, provide a kind of easy, nontoxic, the synthetic method of efficient pyronin derivative dye.

A synthetic method for pyronin derivative dye, comprises the following steps:

(1) utilize carbene reaction to make pyronin directly obtain pyronin ketone and pyronin thioketones;

(2) pyronin thioketones and amine or halohydrocarbons reaction obtain pyronin derivative dye.

Described pyronin utilizes highly basic to make it form Cabbeen intermediate, then generates pyronin ketone or pyronin thioketones with oxygen or sulfur reaction, and wherein said highly basic is trimethyl carbinol first.

Described pyronin thioketones directly and halohydrocarbons reaction obtain sulfo-pyronin derivative dye.

Described pyronin thioketones directly and amine be obtained by reacting ammonia for pyronin derivative dye.

The present invention has following beneficial effect compared with prior art:

1. present invention, avoiding and use highly toxic substance potassium cyanide, adopt the sulphur of non-toxic inexpensive, thus eliminate the danger in experimentation, decrease the pollution to environment, be conducive to producing in enormous quantities.

2. step of the present invention is simple, only needs two steps, and synthesis whole process needs the time less than 2 days, and synthetic method in the past will experience 5 steps, needs the time of 5-6 days, and the present invention substantially reduces generated time, thus improves combined coefficient.

3. temperature of reaction used in the present invention is lower, only need 70 DEG C or room temperature, and synthetic method in the past needs 100 DEG C, and the present invention has energy-saving and cost-reducing advantage, effectively reduces production cost.

4. the product yield of the inventive method synthesis is high, and purity is high, and synthetic method total recovery is in the past less than 15%, and the total recovery of the inventive method can reach 40%-50%.

Embodiment

1. the synthesis of pyronin thioketones or ketone, for thioketones

Step: at normal temperatures, 0.5 (1.66mmol) pyronin Y and 0.53g (16.6mmol) sulphur is added respectively in 50ml round-bottomed flask, add the tetrahydrofuran (THF) that 20ml is refining again, then 0.056g (4.98mmol) potassium tert.-butoxide is added while stirring, after adding, reaction flask is put into oil bath, 70 DEG C of heating reflux reaction 10h.Then above-mentioned reaction system is cooled to room temperature, filter, filter cake washed with dichloromethane, use column chromatography purification (eluent: PE:DCM=1:1) after filtrate is spin-dried for, obtain pyronin thioketones 0.27g, yield is 55%. ¹H NMR (300 MHz, CDCl ₃) δ 8.70 (d, J= 9.2 Hz, 2H), 6.75 (dd, J= 9.2, 2.3 Hz, 2H), 6.43 (d, J= 2.3Hz, 2H), 3.13 (s, 12H). ¹³C NMR (75 MHz, CDCl ₃) δ 196.26, 154.58 , 153.03 , 131.80 , 120.07 , 110.52 , 96.06 , 40.24 . ESI-MS: [M+H] ⁺=299.2。

2. the synthesis of sulfo-pyronin derivative dye, with Nu=SC ₂ h ₅ for example

Step: at normal temperatures, adds 0.03g (0.1mmol) pyronin thioketones, 10 ml anhydrous acetonitriles, then adds iodoethane, then reflux 2h in 50ml round-bottomed flask.Be spin-dried for solvent and obtain crude product, column chromatography (eluent: DCM:EtOH=30:1) is separated to obtain dark green solid, productive rate 95%. ¹H NMR (300 MHz, DMSO) δ 8.22 (d, J= 9.6 Hz, 2H), 7.25 (dd, J= 9.6, 2.5 Hz, 2H), 6.84 (d, J= 2.5 Hz, 2H), 3.30 (s, 12H), 3.24(q, J= 7.3 Hz, 2H), 1.20 (t, J= 7.3 Hz, 3H). ¹³C NMR (75 MHz, DMSO) δ 157.89 , 157.43, 156.26, 131.20, 116.25, 115.27, 96.49, 41.06, 33.48, 15.85. ESI-MS: [M]+=327.2。

3. ammonia for the synthesis of pyronin derivative dye, for NuH=O-Phenylene Diamine

Step: at normal temperatures, adds 0.1g (0.335mmol) pyronin thioketones in 50ml round-bottomed flask, then adds 15ml anhydrous methylene chloride and make it dissolve, and then slowly adds 113 μ l Trifluoromethanesulfonic anhydrides, stirring at room temperature 10min; Then dropwise instill O-Phenylene Diamine (10eq) dichloromethane solution with constant pressure funnel, drip rear stirring at room temperature 10h.Then be spin-dried for by the solvent of above-mentioned reaction, then use acetonitrile and re-crystallizing in ethyl acetate, filter out solid, obtain crude product, then use column chromatography purification (eluent: DCM:EA=2:1), obtain yellow solid 84mg, yield is 70%. ¹H NMR (300 MHz, MeOD) δ 7.78 (d, J= 9.5 Hz, 2H), 7.25 (t, J= 7.6 Hz, 1H), 7.09 (d, J= 7.8 Hz, 1H), 6.96 (d, J= 7.8, 1H), 6.81 (t, J= 7.6 Hz, 1H), 6.76 (dd, J= 9.5, 2.5Hz, 2H), 6.71 (d, J= 2.5 Hz, 2H), 3.18 (s, 12H). ¹³C NMR (75 MHz, MeOD) δ 157.01, 155.46, 154.03, 147.21, 143.91, 129.31, 126.98, 126.52, 117.72, 116.26, 110.67, 102.83, 96.68, 38.80. ESI-MS: [M] ⁺=373.3。

Claims

1. a synthetic method for pyronin derivative dye, comprises the following steps:

(1) utilize carbene reaction to make raw material pyronin directly obtain pyronin ketone and pyronin thioketones;

2. the synthetic method of a kind of pyronin derivative dye according to claim 1, is characterized in that described pyronin utilizes highly basic to make it form Cabbeen intermediate, then generates pyronin ketone or pyronin thioketones with oxygen or sulfur reaction.

3. the synthetic method of a kind of pyronin derivative dye according to claim 1, it is characterized in that described pyronin thioketones directly and halohydrocarbons reaction obtain sulfo-pyronin derivative dye.

4. the synthetic method of a kind of pyronin derivative dye according to claim 1, it is characterized in that described pyronin thioketones directly and amine be obtained by reacting ammonia for pyronin derivative dye.

5. the synthetic method of a kind of pyronin derivative dye according to claim 2, is characterized in that described highly basic is trimethyl carbinol first.