超声微反应器内三硝基间苯三酚合成工艺研究

doi:10.11949/0438-1157.20220258

摘要/Abstract

摘要：

三硝基间苯三酚（TNPG）是重要的医药中间体，通常以间苯三酚（PG）为原料，在间歇反应釜中经硝化合成。该工艺存在反应时间长、能耗高、安全性差等问题，亟需开展新型连续合成工艺研究。在超声微反应器中开展了PG混酸硝化过程研究，通过引入超声解决微通道中高黏流体混合差和固体产物易造成通道堵塞的难题，实现TNPG连续合成并大幅缩短了反应时间。此外，基于对原料和产物的质谱等分析，初步探讨了反应路径和行为特征。在优化工艺条件下（PG浓度：1.0 mol/L；硝酸与PG摩尔比：4；反应温度：40℃；停留时间6~10 min），TNPG收率可达80%，固体纯度大于98%。

关键词: 微通道, 微反应器, 超声微反应器, 硝化, 混合, 过程强化

Abstract:

Trinitrophloroglucinol (TNPG) is an important pharmaceutical intermediate. It is usually synthesized from phloroglucinol (PG) by nitration in a batch reactor. This technology has the problems such as long reaction time, high energy consumption, and poor safety. To develop a novel technology for continuous synthesis is necessary. The process of PG nitration with mixed acid was investigated in an ultrasonic microreactor. By introducing ultrasound, the problems of low mixing of viscous fluids and solid-product clogging were solved, which enabled continuous synthesis of TNPG in much shorter reaction time. Additionally, through mass spectrometry analysis of reactant and product solutions, the reaction mechanism and reaction characteristics were revealed preliminarily. Under optimized conditions (PG concentration, 1.0 mol/L; molar ratio of nitric acid to PG, 4; temperature, 40℃), a yield of 80% and TNPG purity of more than 98% was obtained in reaction time of 6—10 min.

Key words: microchannel, microreactor, ultrasonic microreactor, nitration, mixing, process intensification

中图分类号:

TQ 243

侯跃辉, 刘璇, 廉应江, 韩梅, 尧超群, 陈光文. 超声微反应器内三硝基间苯三酚合成工艺研究[J]. 化工学报, 2022, 73(8): 3597-3607.

Yuehui HOU, Xuan LIU, Yingjiang LIAN, Mei HAN, Chaoqun YAO, Guangwen CHEN. Synthesis process of trinitrophloroglucinol in an ultrasonic microreactor[J]. CIESC Journal, 2022, 73(8): 3597-3607.

图/表 23

图1 间苯三酚（PG）混酸硝化反应机理[6]

Fig.1 Nitrification mechanism of phloroglucinol(PG)[6]

图2 PG硝化实验装置示意图

Fig.2 Experimental device for nitration of PG

图3 典型反应液组成色谱图与浓度-面积峰校正曲线

Fig.3 Typical chromatographic spectra of the composition of reaction solution and the calibration curve

表1 外标法测定值与设定值比较

Table 1 Comparison between measurement by external standard method and set values

Sample No.	设定浓度/(mol/L)		外标法测定浓度/(mol/L)
Sample No.	PG	TNPG	PG	PG-S	PG总量	TNPG
1	0.0412	0.0061	0.0105	0.0332	0.0437	0.0061
2	0.0212	0.0047	0.0059	0.0181	0.0240	0.0047
3	0.0419	0.0049	0.0106	0.0313	0.0419	0.0048

表2 不同温度下反应物黏度

Table 2 Reactant viscosity at different temperatures

温度/℃	黏度/(mPa·s)
温度/℃	98%硫酸^[19-20]	PG溶液（1 mol/L）	硝硫混酸（硝硫比1/3.9）
10	35.1	134.1	62.6
20	25.8	87.1	50.8
30	17.1	57.5	31.3
40	12.9	31.3	22.7

表3 室温（18℃）下甘油-水溶液和甘油-乙醇溶液黏度

Table 3 Viscosities of glycerol-water mixture and glycerol-ethanol mixtures at room temperature （18℃）

溶液/%（质量）	黏度/(mPa∙s)
甘油/水
80	69.6
85	135.9
甘油/乙醇
20	2.82
65	47.8

图4 超声功率对超声空化与混合的影响（80%甘油/水-20%甘油/乙醇）

Fig.4 The effect of ultrasonic power on the cavitation and mixing in the channel (80% glycerol/water-20% glycerol/ethanol)

图5 流速对超声空化与混合的影响（85%甘油/水-20%甘油/乙醇，50 W）

Fig.5 The effect of flow velocity on the cavitation and mixing in the channel (85% glycerol/water-20% glycerol/ethanol, 50 W)

图6 流体混合时间（另一相为20%甘油/乙醇溶液）

Fig.6 The mixing time of the ultrasonic mixing process (the other phase was 20% glycerol/ethanol solution)

图7 流体黏度对超声空化与混合的影响（8.50 mm/s, 50 W）

Fig.7 The effect of fluid viscosity on the cavitation and mixing in the channel (8.50 mm/s, 50 W)

图8 超声功率对TNPG收率的影响

Fig.8 Effect of ultrasonic power on the yield of trinitrophloroglucinol (TNPG)

图9 N/PG对TNPG收率的影响

Fig.9 Effect of reactant ratio on the yield of TNPG

图10 反应温度对TNPG收率的影响

Fig.10 Effect of reaction temperature on the yield of TNPG

图11 混酸含水量对TNPG收率的影响

Fig.11 Effect of water content of mixed acid on the yield of TNPG

表4 不同工艺中硫酸用量对比

Table 4 Comparison of sulfuric acid usage between different process conditions

工艺	PG反应液	硝化试剂	整体		两相流量比（混酸/PG）
工艺	C_PG/(mol/L)	N/S	S/PG	N/PG	两相流量比（混酸/PG）
本工艺	1.0	1/3.9	34.1/1	4/1	1
Cantillo等^[18]	1.0	1/12.3	54.6/1	3/1	2
釜式^[5]	1.14	1/1.25	20.8/1	4/1	—

图12 不同溶解时间下的间苯三酚浓硫酸溶液

Fig.12 Concentrated sulfuric acid solution of PG under different preparation time

图13 间苯三酚硝化反应路径

Fig.13 Nitration path of PG

图14 3,5-二硝基-2,4,6-三羟基苯磺酸归一化百分比

Fig.14 Normalized percentage of 3,5-dinitro-2,4,6-trihydroxybenzene sulfonic acid

图15 二级反应LN-t关系(图中点为实验结果，线为拟合数据)

Fig.15 LN-t relation of second order reaction

图16 简化反应模型下的Arrhenius曲线

Fig.16 Arrhenius curve of the simplified reaction model

图A1 三硝基间苯三酚固体样品液相谱图

Fig.A1 Composition of trinitrophloroglucinol solid sample

图A2 溶解30 min的间苯三酚浓硫酸溶液质谱图

Fig.A2 Mass spectrogram of composition of sulfuric acid solution of phloroglucinol dissolved for 30 min

图A3 溶解24 h的间苯三酚浓硫酸溶液质谱图因为脱去了两个质子使质荷比变化,图A3中分子量为141.9648和181.9429的质谱峰对应的是二磺化间苯三酚和三磺化间苯三酚的半峰

Fig.A3 Mass spectrogram of composition of sulfuric acid solution of phloroglucinol dissolved more than 24 h

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