Preparation method of 4-(2-pyridylazo)resorcinol

Abstract

The invention discloses a preparation method of 4-(2-pyridylazo)resorcinol: using ethanol as a solvent, 2-aminopyridine first undergoes a diazotization reaction with isoamyl nitrite, and then sodium ethoxide is added in batches to generate an ethanol solution of diazonium sodium salt; then the temperature is lowered to 0-10 °C, and an ethanol solution of resorcinol is started to be dropped to undergo an azo reaction to generate azo disodium salt. The ethanol solvent is concentrated, and then pure water is added for dissolution. Then, methyl tert-butyl ether is used to extract impurities, and the solid obtained after concentrating the aqueous phase is suspended and washed with acetone to obtain intermediate II. Intermediate II is then acidified to obtain a crude product; finally, the crude product is recrystallized with a certain proportion of ethanol and water to obtain a dark yellow-red solid, which is analyzed by inspection and is the target product 4-(2-pyridylazo)resorcinol. The high-purity 4-(2-pyridylazo)resorcinol prepared by the invention has an HPLC purity of over 99.5% and a total yield of over 90%.

Description

Technical Field

[0001] The invention relates to a preparation method of 4-(2-pyridyl azo) resorcinol, and belongs to the technical field of synthesis of organic azo dyes and application research in transition metal photometric analysis and detection. Background Art

[0002] With the development of industrial economy, the market demand for organic dyes is increasing. According to statistics, about 2 / 3 of the dyes in the world are synthetic dyes. Therefore, the synthesis research of new organic dyes has become a hot spot for many chemical companies and scientific research institutions. At present, the more popular organic dyes in domestic research include thiophene, coumarin, triphenylamine, porphyrin and other dyes. The latest developed new varieties of organic dyes include condensed azo, DPP, dioxazine and so on.

[0003] 4-(2-pyridyl azo) resorcinol is also a new type of organic dye belonging to the azo class, and can also be detected by photometric analysis of transition metals, and has very high application value. Therefore, the synthesis of the new organic dye compound 4-(2-pyridyl azo) resorcinol is of great research value. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a most economical and applicable process for preparing 4-(2-pyridyl azo) resorcinol, which has the advantages of easy availability of required process raw materials, low price, high yield, simple operation, no harsh reaction requirements, and easy industrialization.

[0005] In order to solve the above problems, the present invention provides a method for preparing 4-(2-pyridyl azo) resorcinol, comprising the following steps:

[0006] Step 1): Using ethanol as solvent, add 2-aminopyridine at 20-25°C, stir and dissolve, cool to 5-10°C, start to drop isoamyl nitrite, the solution becomes a yellow transparent solution, and exothermic phenomenon occurs; after the drop is complete, react at 20-25°C, cool to 0-5°C, then add sodium ethoxide in batches, stir at room temperature overnight after addition, and obtain intermediate I for standby use;

[0007] Step 2): The reaction solution of the intermediate I obtained in step 1) is cooled to 0-10°C, and the ethanol solution of resorcinol is added dropwise. After the addition is completed, the temperature is restored to room temperature (20-25°C), and the reaction is stirred overnight to mature. The reaction solution is yellow-red;

[0008] Step 3): The reaction solution obtained in step 2) is concentrated under reduced pressure at 45°C to remove ethanol, then pure water is added to dissolve, and then extracted and separated with methyl tert-butyl ether, and the upper organic phase is discarded. The obtained aqueous phase is filtered and concentrated to obtain a large amount of solids, and the solids are then suspended and washed with acetone and vacuum dried to obtain intermediate II;

[0009] Step 4): Add the intermediate II obtained in step 3) into pure water, heat to dissolve, filter out the insoluble matters, then dropwise add concentrated hydrochloric acid to adjust the pH of the filtrate to 5 - 6. Dark red - black solids will precipitate. Filter by suction. The filter cake is then slurried and washed with ethanol and dried to obtain the crude product.

[0010] Step 5): Purify the crude product obtained in step 4). First, dissolve it by heating with ethanol, add activated carbon, filter while it is hot. Then add the filtrate into pure water to precipitate dark yellow - red solids by squeezing. Filter by suction. The filter cake is dried by blowing air at 60 °C to obtain 4 - (2 - pyridylazo)resorcinol.

[0011] Preferably, step 1) is specifically as follows: First, add ethanol into a container. Under the condition of 20 - 25 °C, add 2 - aminopyridine in batches while stirring. After stirring and dissolving, cool down to 5 - 10 °C, and start to add isoamyl nitrite. The solution turns into a yellow - transparent solution with an exothermic phenomenon. After dropping, let the reaction age at 20 - 25 °C for 2 h, then cool it to 0 - 5 °C in an ice - water bath, and then add sodium ethoxide in batches. After adding, stir at room temperature overnight to obtain intermediate I for standby. Among them, the volume ratio of the required ethanol to the weight of 2 - aminopyridine is 15 - 20 mL / g, the molar ratio of isoamyl nitrite to 2 - aminopyridine is (1.5 - 2):1, and the molar ratio of sodium ethoxide to 2 - aminopyridine is (1.5 - 2):1.

[0012] Preferably, step 2) is specifically as follows: Cool the reaction solution of intermediate I obtained in step 1) to 0 - 10 °C, and then start to slowly dropwise add the ethanol solution of resorcinol. There is heat release, and the temperature is controlled below 10 °C. After dropping, keep the temperature at 0 - 10 °C for 2 h for reaction, and then restore to room temperature (20 - 25 °C) and stir overnight for aging. The reaction solution is yellow - red. Among them, the volume ratio of the required ethanol to the weight of resorcinol is 2 - 3 mL / g, and the molar ratio of resorcinol to 2 - aminopyridine is (1.5 - 2):1.

[0013] Preferably, step 3) is specifically as follows: After concentrating the reaction solution obtained in step 2) under reduced pressure at 45 °C to remove ethanol, add pure water to dissolve it, then extract and layer with methyl tert - butyl ether. Discard the upper organic phase. Filter and concentrate the obtained aqueous phase to obtain a solid. The solid is then slurried and washed with acetone and dried under vacuum to obtain intermediate II. Among them, the volume ratio of the added pure water to the weight of the residue after concentration is 8 - 10 mL / g, the volume ratio of the methyl tert - butyl ether required for extracting impurities each time to the volume of pure water is 1:2, and extraction needs to be carried out 2 times.

[0014] Preferably, step 4) is specifically as follows: Add the intermediate II obtained in step 3) to pure water, heat to dissolve, filter off the insoluble matter, then dropwise add concentrated hydrochloric acid to adjust the pH of the filtrate to 5-6. Dark red and black solids will precipitate out. Perform suction filtration, and then slurry and wash the filter cake with ethanol, and dry to obtain the crude product; wherein, the volume ratio of the added pure water to the weight of the intermediate II is 8-10 mL / g.

[0015] Preferably, step 5) is specifically as follows: Purify the crude product obtained in step 4). First, heat and dissolve it with ethanol, add activated carbon, filter while it is hot, then add the filtrate to pure water to precipitate yellowish-red solids by squeezing, perform suction filtration, and dry the filter cake by blowing air at 60 °C; wherein, the volume ratio of the ethanol required for recrystallization to the weight of the crude product is 5-8 mL / g, and the volume ratio of ethanol to pure water is 1:3.

[0016] The present invention uses 2-aminopyridine, resorcinol, and isoamyl nitrite, which are cheap and easily available in industry, as the main raw materials, and common auxiliary materials such as sodium ethoxide, ethanol, acetone, methyl tert-butyl ether, and concentrated hydrochloric acid. The target product crude is synthesized in 3 steps, and after purification by recrystallization, a high-purity product 4-(2-pyridylazo)resorcinol is obtained. The HPLC purity reaches over 99.5%, and the total yield is over 90%. The present invention has the advantages of low cost of synthetic raw materials, simple process, good reaction controllability, high reaction conversion rate, etc., and is suitable for industrial production.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] 1. The raw materials required for synthesis in the present invention, such as 2-aminopyridine, resorcinol, isoamyl nitrite, sodium ethoxide, ethanol, acetone, methyl tert-butyl ether, and concentrated hydrochloric acid, are all cheap, easily available industrial products. The synthesis process has the advantages of mild reaction conditions, convenient operation; easy reaction control, few side reactions, high reaction conversion rate; and simple purification of the target product. The whole process is suitable for industrial production.

[0019] 2. The present invention synthesizes 4-(2-pyridylazo)resorcinol in 3 steps. Among them, after 2-aminopyridine undergoes a diazotization reaction with isoamyl nitrite, it reacts with sodium ethoxide to generate diazonium sodium salt, that is, intermediate I. The occurrence of side reactions is mainly reduced and the conversion rate is improved by controlling the reaction temperature and the feeding ratio of materials. Next, it reacts with resorcinol to produce azo disodium salt, that is, intermediate II, and finally, the crude product is obtained after acidification with hydrochloric acid. The crude product obtained in this way is then purified by recrystallization with a mixed solvent of ethanol and water to obtain high-purity 4-(2-pyridylazo)resorcinol. The HPLC purity reaches over 99.5%, and the total yield is over 90%. Specific Embodiments

[0020] To make the present invention more obvious and understandable, the following is a detailed description with preferred embodiments.

[0021] Examples 1 and 2 provide a method for preparing 4-(2-pyridylazo)resorcinol. The chemical equation for the synthesis process is as follows:

[0022]

[0023] Example 1

[0024] A process for preparing 4-(2-pyridylazo)resorcinol, the steps are as follows:

[0025] (1) Prepare a 10L glass reaction kettle. Under the condition of 20 - 25°C, first add 4.5L of ethanol and stir. Then add 2-aminopyridine (300g, 3.2mol) in batches. After stirring and dissolving, cool the mixture to 5 - 10°C in an ice-water bath. At 5°C, start to slowly drip isoamyl nitrite (562g, 4.8mol). During the dripping process, heat is released and it becomes a yellow transparent solution. After dripping, the reaction is aged for 2h under the condition of 20 - 25°C. The reaction solution is cooled to 0 - 5°C in an ice-water bath, and then sodium ethoxide (327g, 4.8mol) is added in batches. After adding, stir and age overnight at room temperature of 20 - 25°C to obtain Intermediate I for later use.

[0026] (2) Use an ice-water bath to cool the reaction solution of Intermediate I to 0 - 10°C, and then start to slowly drip a solution of resorcinol (528.5g, 4.8mol) in ethanol (1060mL). After dripping, remove the ice-water bath and restore to room temperature, then heat to reflux, and control the internal temperature of the reaction solution at 105 - 110°C for 3h of aging;

[0027] (3) After the reaction is completed, remove the ethanol in the reaction solution by vacuum concentration at 45°C. After concentration, 1.05kg of residue is obtained. Then add 8.4L of pure water and stir to dissolve. Then extract with methyl tert-butyl ether (4.2L×2), let it stand and separate layers, remove the organic phase. The collected aqueous phase is filtered and concentrated to obtain a large amount of dark red-black solid; the solid is then washed by suspension with 2L of acetone and filtered. The filter cake is dried in vacuo at 50°C for 24h to obtain 795g of dry Intermediate II;

[0028] (4) Prepare a 10L glass reaction flask, first add 6.4L of pure water, add 795g of Intermediate II while stirring, then heat to 80 - 90°C, the solid dissolves, and the insoluble matter is filtered off while it is hot. After cooling to room temperature, add concentrated hydrochloric acid (550mL) dropwise to adjust the pH of the solution to 5 - 6, and a large amount of dark red-black solid precipitates. Filter by suction, and the filter cake is washed by suspension with a small amount of ethanol (2L×2) and dried to obtain 635g of crude product;

[0029] (5) Prepare a 5 L glass reaction flask. First, add 3.2 L of ethanol, and while stirring, add 635 g of the crude product. Then heat to 90 - 100 °C until the solid dissolves. Add activated carbon (15 g), filter while hot under pressure. Then slowly add the filtrate to 9.6 L of pure water while stirring. A large amount of yellow - red solid precipitates. After adding, place it in the refrigerator for 2 h and then filter by suction. The filter cake is dried in a blast dryer at 60 °C for 48 h to obtain 623 g of the dry product.

[0030] The nuclear magnetic resonance processing data, HPLC, and total N of the above - prepared compound were detected as follows:

[0031] 1H - NMR (DMSO, 400 MHz, δ ppm): δ = 8.52 (1H, d), 7.89 - 7.92 (1H, t), 7.71 - 7.73 (1H, d), 7.46 - 7.48 (1H, d), 7.34 - 7.35 (1H, t), 6.43 - 6.46 (1H, dd), 6.13 (1H, d), 2.63 - 3.74 (2H, br) ppm

[0032] HPLC: 99.5%

[0033] Total N: 99%

[0034] From the above data, it can be seen that the above - prepared compound is 4 - (2 - pyridylazo)resorcinol, and the total yield is 90.5%.

[0035] Example 2

[0036] A preparation method of 4 - (2 - pyridylazo)resorcinol is as follows:

[0037] (1) Prepare a 10 L glass reaction kettle. Under the condition of 20 - 25 °C, first add 6.0 L of ethanol and stir. Then add 2 - aminopyridine (300 g, 3.2 mol) in batches. After stirring and dissolving, cool to 5 - 10 °C in an ice - water bath. Under the condition of 5 °C, start to slowly dropwise add isoamyl nitrite (749 g, 6.4 mol). During the dropping process, there is heat release and it becomes a yellow - transparent solution. After dropping, let the reaction age at 20 - 25 °C for 2 h. Cool the reaction solution to 0 - 5 °C in an ice - water bath, and then add sodium ethoxide (436 g, 6.4 mol) in batches. After adding, stir and age overnight at room temperature (20 - 25 °C) to obtain Intermediate Ⅰ for later use.

[0038] (2) Use an ice - water bath to cool the reaction solution of Intermediate Ⅰ to 0 - 10 °C, and then start to slowly dropwise add a solution of resorcinol (705 g, 6.4 mol) in ethanol (2.1 L). After dropping, remove the ice - water bath and restore to room temperature, then heat to reflux, and control the internal temperature of the reaction solution at 105 - 110 °C for 3 h to age;

[0039] (3) After the reaction is completed, the ethanol in the reaction solution is removed by concentration under reduced pressure at 45 °C. After concentration, 1.15 kg of residue is obtained. Then, 11.5 L of pure water is added and stirred until dissolved. Then, it is extracted with methyl tert-butyl ether (5.7 L × 2), allowed to stand for layering, the organic phase is removed, and the collected aqueous phase is filtered and concentrated to obtain a large amount of dark red-black solid; the solid is then washed by suspension with 2 L of acetone and filtered by suction. The filter cake is dried in vacuo at 50 °C for 24 h to obtain 803 g of dry intermediate II;

[0040] (4) Prepare a 10 L glass reaction flask, first add 8 L of pure water, add 803 g of intermediate II while stirring, then heat to 80 - 90 °C. The solid dissolves, and the insoluble matter is filtered off while it is hot. After cooling to room temperature, concentrated hydrochloric acid (550 mL) is added dropwise to adjust the pH of the solution to 5 - 6. A large amount of dark red-black solid precipitates. It is filtered by suction, and the filter cake is washed by suspension with a small amount of ethanol (2 L × 2) and dried to obtain 650 g of crude product;

[0041] (5) Prepare a 5 L glass reaction flask, first add 5.2 L of ethanol, add 650 g of the crude product while stirring, then heat to 90 - 100 °C. The solid dissolves, activated carbon (15 g) is added, and it is filtered under pressure while it is hot. Then the filtrate is slowly added to 15.6 L of pure water while stirring. A large amount of yellow-red solid precipitates. After adding, it is placed in the refrigerator for 2 h and then filtered by suction. The filter cake is dried by air blowing at 60 °C for 48 h to obtain 631 g of dry product.

[0042] The nuclear magnetic resonance processing data, HPLC, and total N of the above-prepared compound are detected as follows:

[0043] 1H-NMR (DMSO, 400 MHz, δ ppm): δ = 8.51 (1H, d), 7.89 - 7.93 (1H, t), 7.71 - 7.74 (1H, d), 7.45 - 7.48 (1H, d), 7.33 - 7.35 (1H, t), 6.44 - 6.46 (1H, dd), 6.12 (1H, d), 2.63 - 3.75 (2H, br) ppm

[0044] HPLC: 99.6%

[0045] Total N: 99%

[0046] From the above data, it can be seen that the above-prepared compound is 4-(2-pyridylazo)resorcinol, and the total yield is 91.6%.

Claims

1. A method for preparing 4-(2-pyridyl azo) resorcinol, It is characterized in that The steps include: Step 1): first add ethanol to a container, and add 2-aminopyridine in batches while stirring at 20-25°C. After stirring and dissolving, cool to 5-10°C, start adding isoamyl nitrite, and the solution becomes a yellow transparent solution accompanied by heat release; after the addition is completed, the reaction is matured at 20-25°C for 2h, and then cooled to 0-5°C in an ice water bath, and then sodium ethoxide is added in batches. After the addition is completed, stir at room temperature overnight to obtain intermediate I, which is set aside; wherein the required volume ratio of ethanol to 2-aminopyridine is 15-20mL / g, the molar ratio of isoamyl nitrite to 2-aminopyridine is (1.5-2):1, and the molar ratio of sodium ethoxide to 2-aminopyridine is (1.5-2):1; Step 2): The reaction solution of the intermediate I obtained in step 1) is cooled to 0-10°C, and then the ethanol solution of resorcinol is slowly added dropwise, exothermic, and the temperature is controlled below 10°C. After the addition is completed, the temperature is kept at 0-10°C for 2 hours, and then the temperature is restored to room temperature 20-25°C. The reaction is stirred overnight and matured, and the reaction solution is yellow-red; wherein the required volume ratio of ethanol to the weight of resorcinol is 2-3 mL / g, and the molar ratio of resorcinol to 2-aminopyridine is (1.5-2):1; Step 3): The reaction solution obtained in step 2) is concentrated under reduced pressure at 45°C to remove ethanol, and then pure water is added to dissolve it, and then methyl tert-butyl ether is used for extraction and layering, and the upper organic phase is discarded, and the obtained aqueous phase is filtered and concentrated to obtain a solid, and the solid is then suspended and washed with acetone and vacuum dried to obtain intermediate II; wherein the ratio of the volume of pure water added to the weight of the residue after concentration is 8-10mL / g, and the ratio of the volume of methyl tert-butyl ether required for each extraction of impurities to the volume of pure water is 1:2, and extraction is required twice; Step 4): Add the intermediate II obtained in step 3) into pure water, heat to dissolve, filter out the insoluble matter, then drop concentrated hydrochloric acid, adjust the pH of the filtrate to 5-6, and a dark red-black solid precipitates, filter, and then slurry and wash the filter cake with ethanol, and dry to obtain a crude product; wherein the volume ratio of the added pure water to the weight of the intermediate II is 8-10 mL / g; Step 5): purify the crude product obtained in step 4), first heat it with ethanol to dissolve it, then add activated carbon, filter it while hot, then add the filtrate into pure water to squeeze out the yellow-red solid, filter it with suction, and dry the filter cake at 60°C with air supply; wherein, the volume ratio of ethanol required for recrystallization to the weight of the crude product is 5-8mL / g, and the volume ratio of ethanol to pure water is 1:3.

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