Synthesis process of trinitrophloroglucinol in an ultrasonic microreactor

doi:10.11949/0438-1157.20220258

Abstract

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

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

CLC Number:

TQ 243

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.

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.

Figures/Tables 23

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

Fig.2 Experimental device for nitration of PG

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

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

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

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

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

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

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

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

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

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

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

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

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	—

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

Fig.13 Nitration path of PG

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

Fig.15 LN-t relation of second order reaction

Fig.16 Arrhenius curve of the simplified reaction model

Fig.A1 Composition of trinitrophloroglucinol solid sample

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

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

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