Method for preparing N, N '-bis (2, 2, 6, 6-tetramethyl-4-piperidyl) isophthalamide by using continuous flow micro-reaction device

Abstract

The invention discloses a method for preparing N, N '-bis (2, 2, 6, 6-tetramethyl-4-piperidyl) isophthalamide by using a continuous flow micro-reaction device. The device comprises an acylating chlorination micro-reactor module, a condensation micro-reactor module and a neutralization module which are connected in series, the preparation method comprises the following steps: synthesizing isophthaloyl chloride by taking isophthalic acid and thionyl chloride as reaction materials, carrying out condensation reaction by taking isophthaloyl chloride and 2, 2, 6, 6-tetramethyl-4-piperidylamine as main raw materials, filtering, collecting a filter cake, washing and drying to obtain an intermediate II; and neutralizing the intermediate II with a sodium hydroxide solution, filtering, collecting a filter cake, washing, and drying to obtain the N, N '-bis (2, 2, 6, 6-tetramethyl-4-piperidyl) isophthalamide as shown in the target compound I. The invention further discloses a preparation method of the N, N'-bis (2, 2, 6, 6-tetramethyl-4-piperidyl) isophthalamide. The method is mild in reaction condition, short in time and simple to operate, the yield and the product purity can be improved, and byproducts such as waste acid and fatty alcohol are not generated in the reaction process.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of light stabilizers, and specifically relates to a method for preparing N,N′-bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide by utilizing a continuous flow micro-reaction device. Background Art

[0002] N,N′-bis(2,2,6,6-tetramethyl-4-piperidinyl)-isophthalamide is an excellent light stabilizer. It is a white crystalline solid with low coloring, low volatility, and high acid and alkali resistance. It is widely used in polymer materials such as polyethylene, polypropylene, polyvinyl chloride, and polyurethane.

[0003] At present, the preparation methods of N,N′-bis(2,2,6,6-tetramethyl-4-piperidinyl)-isophthalamide mainly include: acylation synthesis method of isophthaloyl chloride and 2,2,6,6-tetramethylpiperidinamine (such as Chinese patents CN201110304707.8, CN201310494639.5, CN201610033043.9, CN201310110901.1) and ester exchange method of isophthalic acid ester and 2,2,6,6-tetramethylpiperidinamine (such as Chinese patents CN201510483741.4, CN201710652766.1, CN201710111609.X). However, the acylation synthesis method will produce a large amount of waste acid, causing three wastes pollution; the ester exchange method will produce by-products such as fatty alcohols. Therefore, it is necessary to develop a new method for preparing N,N′-bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide. Summary of the invention

[0004] The object of the present invention is to provide a method for preparing N,N′-bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide by using a continuous flow micro-reactor. The method has mild reaction conditions, short reaction time and simple operation, can improve the reaction yield and product purity, and does not generate byproducts such as waste acid and fatty alcohol during the reaction process.

[0005] To achieve the above object, the technical solution adopted by the present invention is: a method for preparing N, N'-di(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide by using a continuous flow microreactor, the continuous flow microreactor comprises an acyl chloride microreactor module, a condensation microreactor module and a neutralization module, and the modules are connected in series; wherein the acyl chloride microreactor module comprises a feeding unit, a reaction zone and a quenching zone; the condensation microreactor module comprises a feeding unit and a reaction zone; the neutralization module comprises a feeding unit and a neutralization reactor; the specific steps are:

[0006] (1) At room temperature, using an acyl chloride microreactor module as a reaction area, a dichloromethane solution of isophthalic acid and thionyl chloride as reaction materials are respectively introduced into the reaction area through a metering pump in a feeding unit to perform an acyl chloride reaction, and after the reaction is completed, the reaction is carried out in a quenching area to perform a quenching reaction to obtain a crude isophthaloyl chloride product;

[0007] (2) At room temperature, a condensation microreactor module is used as a reaction area, 2,2,6,6-tetramethyl-4-piperidinamine and isophthaloyl chloride prepared in step (1) are used as main raw materials, which are dissolved in toluene and introduced into the reaction area through a high-pressure infusion feed pump of a feeding unit for precooling and mixing reaction, and a condensation reaction is carried out under a catalyst. The temperature of the condensation microreactor module system is controlled by a refrigeration and heating circulator in the reaction area; the amount ratio of isophthaloyl chloride, 2,2,6,6-tetramethyl-4-piperidinamine and catalyst is 1:2.0-2.2:0.05:0.1 in terms of molar amount, the condensation reaction temperature is 110-120°C, and the reaction time is 5-10h. Since the intermediate II has poor solubility in organic solvents, the precipitate gradually increases as the reaction proceeds. The reaction is carried out until the precipitation is complete, the reaction solution is filtered, the filter cake is washed with an anhydrous solvent, and then dried to obtain the intermediate II. The structural formula of the intermediate II is

[0008] (3) At room temperature, with the neutralization module as the post-processing area, the intermediate II is stirred and mixed with water, and then added to the sodium hydroxide solution through the high-pressure infusion feed pump of the feeding unit for neutralization, and then filtered and washed with water. The filter cake is dried to obtain N,N-di(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide shown in the target compound I. The structural formula of the target compound I is

[0009] Preferably, in step (2), the catalyst is one of aluminum trichloride, ferric trichloride, zinc dichloride, and dimethylformamide.

[0010] Preferably, in step (2), the catalyst is aluminum chloride.

[0011] Preferably, the reaction time is 8 h.

[0012] Furthermore, in step (2), the filtrate obtained by filtering the reaction liquid and the washing liquid obtained after washing the filter cake are collected and used as the reaction solvent in the next batch of step (2) for preparing N,N′-di(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide.

[0013] The reaction scheme of the present invention is as follows:

[0014]

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] (1) The present invention first uses isophthalic acid and thionyl chloride as reaction raw materials to synthesize isophthaloyl chloride, and then directly uses isophthaloyl chloride and 2,2,6,6-tetramethyl-4-piperidinamine to carry out condensation reaction to generate the target product. The reaction conditions are mild, the reaction time is short, the operation is simple, the reaction yield is high, and the product purity is high;

[0017] (2) The present invention selects a suitable organic reagent, toluene, to ensure that isophthaloyl chloride and 2,2,6,6-tetramethyl-4-aminopiperidine are well dissolved in toluene, while intermediate II is poorly soluble in the organic reagent, thereby promoting the complete progress of the reaction; in addition, the organic solvent enables the excess 2,2,6,6-tetramethyl-4-aminopiperidine to be effectively recovered, thereby avoiding the waste of raw materials and saving experimental costs;

[0018] (3) Since the solubility of intermediate II in organic solvents is poor, the mother liquor in the present invention contains only a trace amount of intermediate II and an excess of raw material 2,2,6,6-tetramethyl-4-aminopiperidine in addition to the organic solvent, and can be used for the next batch of production. This method not only reduces the unit consumption of raw materials, but also does not produce wastewater containing 2,2,6,6-tetramethyl-4-aminopiperidine with poor biodegradability. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is the hydrogen spectrum of the target product prepared in Example 1;

[0020] Figure 2 The carbon spectrum of the target product prepared in Example 1;

[0021] Figure 3 It is a process flow chart of the present invention. DETAILED DESCRIPTION

[0022] The present invention is further described in detail below with reference to the accompanying drawings and embodiments.

[0023] Example 1

[0024] like Figure 3 A method for preparing N,N′-bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide using a continuous flow microreactor is shown, wherein the continuous flow microreactor comprises an acyl chloride microreactor module, a condensation microreactor module and a neutralization module, and the modules are connected in series; wherein the acyl chloride microreactor module comprises a feeding unit, a reaction zone and a quenching zone; the condensation microreactor module comprises a feeding unit and a reaction zone; the neutralization module comprises a feeding unit and a neutralization reactor; and the specific steps are:

[0025] (1) Dissolve 8.3 g of isophthalic acid in 400 mL of dichloromethane and place the resulting solution in injector A; place 40 mL of thionyl chloride in injector B;

[0026] (2) injector A and injector B are respectively introduced into the reactor through metering pumps at flow rates of 6 mL / min and 0.6 mL / min for reaction, reacted at room temperature for 2 h, and after the reaction is completed, enter the quenching zone for quenching reaction to obtain crude isophthaloyl chloride;

[0027] (3) 8.5 g of 2,2,6,6-tetramethyl-4-piperidinamine was dissolved in 25 mL of toluene, 5.0 g of crude isophthaloyl chloride and 0.15 g of aluminum chloride were added in sequence, and the mixture was introduced into the reaction zone and reacted at room temperature for 8 h. After the reaction, the reaction liquid was filtered, the filter cake was washed with toluene, the mother liquor and the washing liquid were collected for the next batch of production, and the filter cake was vacuum dried to obtain 12.1 g of intermediate II with a yield of 95.2%;

[0028] (4) 12.1 g of the intermediate II obtained and 60 g of water were added to a neutralization reactor and stirred evenly. 7 g of a 30% aqueous sodium hydroxide solution was added dropwise at room temperature until the pH value of the reaction solution was 10. The reaction mixture was filtered and separated. The filter cake was washed with soft water and dried to obtain 10.1 g. The total yield was 92.5% and the melting point was 270-275°C.

[0029] (5) 35 g of the mother liquor recovered in Example 1, 5.0 g of isophthaloyl chloride, 7.7 g of 2,2,6,6-tetramethyl-4-piperidinamine, and 0.15 g of aluminum trichloride were added to a reactor and the reaction was continued at room temperature for 8 h. After the reaction was completed, the reaction liquid was filtered, the filter cake was washed with toluene, and the mother liquor and washing liquid were collected for the next batch of production. The filter cake was vacuum dried to obtain 12.2 g of intermediate II, with a yield of 96.4%.

[0030] (6) 12.2 g of the intermediate II and 60 g of water were added to a reaction flask and stirred evenly. 7 g of a 30% aqueous sodium hydroxide solution was added dropwise at room temperature until the pH value of the reaction solution was 10. The mixture was filtered and separated. The filter cake was washed with soft water and dried to obtain 10.3 g. The total yield was 95.3%. The melting point was 270-275° C. The characterization data are as follows (see the spectra for details). Figure 1 and Figure 2 ):

[0031] 1HNMR(400MHz,MeOD): δ8.24(d,J1.8Hz,1H),7.94-8.01(dd,J7.7,1.8Hz,2H),7.53(t,J7.8Hz,1H),4.37-4.46(tt,J)1 3.8.6,3.8Hz,2H),1.82-1.89(dd,JS12.4,3.7Hz,4H),1.26-12.9(s,12H),1.18-1.25(t,JS12.4Hz,4H),1.14-1.16(s,12H).

[0032] 13 CNMR(101MHz,MeOD)δ167.43,135.07,129.96,128.46,126.02,51.12,43.84,42.88,32.98,26.73.

Claims

1. A method for preparing N,N'-bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide using a continuous flow microreactor, the continuous flow microreactor comprising an acyl chloride microreactor module, a condensation microreactor module and a neutralization module, wherein the modules are connected in series; wherein: The acyl chloride microreactor module includes a feeding unit, a reaction zone and a quenching zone; the condensation microreactor module includes a feeding unit and a reaction zone; the neutralization module includes a feeding unit and a neutralization reactor; and is characterized in that: (1) At room temperature, using an acyl chloride microreactor module as a reaction area, a dichloromethane solution of isophthalic acid and thionyl chloride as reaction materials are respectively introduced into the reaction area through a metering pump in a feeding unit to perform an acyl chloride reaction, and after the reaction is completed, the reaction is carried out in a quenching area to perform a quenching reaction to obtain a crude isophthaloyl chloride product; (2) At room temperature, the condensation microreactor module is used as the reaction area, 2,2,6,6-tetramethyl-4-piperidinamine and the isophthaloyl chloride prepared in step (1) are used as the main raw materials, which are dissolved in toluene and introduced into the reaction area through the high-pressure infusion feed pump of the feeding unit for precooling and mixing reaction, and the condensation reaction is carried out under the catalyst. The temperature of the condensation microreactor module system is controlled by the refrigeration and heating circulator in the reaction area; the amount ratio of the isophthaloyl chloride, 2,2,6,6-tetramethyl-4-piperidinamine and the catalyst is 1:2.0-2.2:0.05:0.1 in terms of molar amount, the condensation reaction temperature is 110-120°C, the reaction time is 5-10h, the reaction is carried out until the precipitation is complete, the reaction solution is filtered, the filter cake is washed with an anhydrous solvent, and then dried to obtain the intermediate II, the structural formula of the intermediate II is (3) At room temperature, the intermediate II is stirred and mixed with water in the neutralization module as the post-processing area, and then added to the neutralization reactor containing sodium hydroxide solution through the high-pressure infusion feed pump of the feeding unit for neutralization, filtration, and water washing. The filter cake is dried to obtain N,N-di(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide shown in the target compound I. The structural formula of the target compound I is 2. A method for preparing N,N'-bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide using a continuous flow microreactor according to claim 1, characterized in that: In step (2), the catalyst is one of aluminum chloride, ferric chloride, zinc dichloride and dimethylformamide.

3. A method for preparing N,N'-bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide using a continuous flow microreactor according to claim 2, characterized in that: In step (2), the catalyst is aluminum chloride.

4. A method for preparing N,N'-bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide using a continuous flow microreactor according to claim 1 or 2, characterized in that: In step (2), the reaction time is 8 h.

5. A method for preparing N,N'-bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide using a continuous flow microreactor according to claim 1 or 2, characterized in that: In step (2), the filtrate obtained by filtering the reaction liquid and the washing liquid obtained after washing the filter cake are collected and used as the reaction solvent in the next batch of preparation of N,N'-di(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide step (1).

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