CN104448898B - A kind of synthetic method of pyronin derivative dye - Google Patents

Abstract

The invention discloses the synthetic method of a kind of pyronin derivative dye, it is with pyronin as raw material, Cabbeen intermediate is generated under the effect of potassium tert-butoxide, Cabbeen generates pyronin thioketones or ketone with sulphur or oxygen reaction again, and pyronin thioketones generates pyronin derivative dye with amine or halohydrocarbons reaction again.The present invention operates safe and simple, and the reaction time is short, and yield and purity are preferable.

Description

A kind of synthetic method of pyronine derivative dye

technical field

The invention relates to a method for synthesizing pyronine derivative dyes.

Background technique

Pyronine derivatives are a class of excellent dyes, which have the advantages of good stability and high fluorescence quantum yield. When the substituting element on the 9-position is sulfur, the dye gives strong red fluorescence; when it is nitrogen, it gives strong green fluorescence. However, the synthesis of this type of dye is relatively difficult at present. The general synthesis method is to first oxidize pyronine into a ketone, and then the ketone carries out a nucleophilic substitution reaction with a nucleophile under the catalysis of trifluoromethanesulfonic anhydride to generate the target product. The process needs to go through 5 steps in total, which takes a long time and has low yield, and a large amount of highly toxic substance potassium cyanide is used in the oxidation step. Therefore, it is very necessary to develop new synthesis techniques.

Contents of the invention

The invention overcomes the disadvantages of using highly toxic potassium cyanide, long reaction time and low yield in the existing synthesis technology, and provides a simple, non-toxic and efficient synthesis method of pyronin derivative dyes.

A synthetic method for pyronine derivative dyes, comprising the following steps:

(1) Utilize carbene reaction to make pyronine directly obtain pyroningone and pyroningthione;

⑵ Reaction of pyronine thione with amines or halogenated hydrocarbons to obtain pyronine derivative dyes.

The pyronine uses a strong base to form a carbene intermediate, and then reacts with oxygen or sulfur to generate pyroningone or pyroninthione, wherein the strong base is tert-butanol methyl.

The pyronine thione is directly reacted with a halogenated hydrocarbon to obtain a thiopyronine derivative dye.

The pyronine thione is directly reacted with an amine to obtain an aminopyronine derivative dye.

Compared with the prior art, the present invention has the following beneficial effects:

1. The present invention avoids the use of highly toxic substance potassium cyanide, and adopts cheap and non-toxic sulfur, thereby eliminating the danger in the experiment process, reducing environmental pollution, and being conducive to mass production.

2. the step of the present invention is simple, only needs two steps, and synthetic whole process needs the time of 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 has shortened synthetic time greatly, thereby Improved synthesis efficiency.

3. The reaction temperature used in the present invention is relatively low, only 70°C or room temperature is required, while the previous synthesis method requires 100°C. The present invention has the advantages of saving energy and reducing consumption, effectively reducing production costs.

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

detailed description

1. Synthesis of pyronin thione or ketone, taking thione as an example

Steps: Add 0.5 (1.66 mmol) pyronin Y and 0.53 g (16.6 mmol) sulfur to a 50 ml round bottom flask at room temperature, then add 20 ml of refined tetrahydrofuran, then add 0.056 g (4.98 mmol) while stirring Potassium tert-butoxide, after the addition, put the reaction bottle into an oil bath, and heat under reflux at 70°C for 10 hours. Then the above reaction system was cooled to room temperature, filtered, the filter cake was washed with dichloromethane, and the filtrate was spin-dried and purified by column chromatography (eluent: PE:DCM=1:1) to obtain pyroninthione 0.27 g, the yield is 55%. ¹ H 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). ¹³ C 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. Synthesis of thiopyronine derivative dyes, taking Nu=SC ₂ H ₅ as an example

Steps: Add 0.03 g (0.1 mmol) pyroninthione, 10 ml anhydrous acetonitrile, and ethyl iodide to a 50 ml round bottom flask at room temperature, then heat to reflux for 2 h. The solvent was spin-dried to obtain a crude product, which was separated by column chromatography (eluent: DCM:EtOH=30:1) to obtain a dark green solid with a yield of 95%. ¹ H 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). ¹³ C 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. Synthesis of aminopyronine derivative dyes, taking NuH=o-phenylenediamine as an example

Steps: Add 0.1g (0.335mmol) pyroninthione to a 50ml round bottom flask at room temperature, then add 15ml anhydrous dichloromethane to dissolve it, then slowly add 113μl trifluoromethanesulfonic anhydride, and stir at room temperature for 10min ; Then use a constant pressure dropping funnel dropwise into the o-phenylenediamine (10eq) methylene chloride solution, and stir at room temperature for 10 hours after the addition. Then the solvent of the above reaction was spin-dried, and then recrystallized with acetonitrile and ethyl acetate, and the solid was filtered out to obtain a crude product, which was separated and purified by column chromatography (eluent: DCM:EA=2:1), to obtain Yellow solid 84mg, yield 70%. ¹ H NMR (300 MHz, MeOD) δ7.78 (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). ¹³ C 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, 96.680, ^ESI 38 373.3.

Claims (5)

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

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

(2) pyronin thioketones and amine or halohydrocarbons reaction obtain pyronin derivative dye, wherein, " Nu " choosing in above formula product From second sulfydryl or 2-amino phenyl amino.

The synthetic method of a kind of pyronin derivative dye the most according to claim 1, is characterized in that described pyronin Utilize highly basic to form it into Cabbeen intermediate, then generate pyronin thioketones with sulfur reaction.

The synthetic method of a kind of pyronin derivative dye the most according to claim 1, is characterized in that described pyronin Thioketones is directly and halohydrocarbons reaction obtains sulphur for pyronin derivative dye.

The synthetic method of a kind of pyronin derivative dye the most according to claim 1, is characterized in that described pyronin Thioketones directly reacts with amine and obtains ammonia for pyronin derivative dye.

The synthetic method of a kind of pyronin derivative dye the most according to claim 2, is characterized in that described highly basic is Potassium tert-butoxide.