模块化微反应系统内溴化间甲基苯甲醚连续合成

doi:10.11949/0438-1157.20200518

摘要/Abstract

摘要：

根据微化工技术发展的主要趋势，针对4-溴-3-甲基苯甲醚间歇非均相合成技术存在的问题，以微筛孔反应器与玻璃微珠填充床为核心功能微设备单元构建了模块化微反应系统，并在此模块化微反应系统内对液-液非均相连续溴化合成4-溴-3-甲基苯甲醚开展研究。通过优化操作条件，在溴浓度( $x B r 2$ )为17.5%（质量分数）、溴与间甲基苯甲醚摩尔比( $n B r 2$ /n_M)为1.01、反应起始温度(T)为 0℃、停留时间为0.78 min条件下，4-溴-3-甲基苯甲醚的收率大于98%，多溴代副产物的含量仅为1%。与传统间歇溴化反应相比，模块化微反应系统内连续溴化反应具有十分明显的优势：可将间歇过程连续化，在保证安全的基础上极大地提升了反应的效率（时空收率为6.5×10⁴ kg/(m³·h)）；另外，该过程是由传质控制的，微反应器的传质性能优异，可极大地改善产品的选择性（多溴代副产物的量减少50%）。该研究为4-溴-3-甲基苯甲醚的连续高效安全合成提供了技术和设备依据。

关键词: 微反应器, 静态混合器, 间甲基苯甲醚, 溴化反应, 连续合成, 过程控制

Abstract:

With the development of microreaction technology and the key issues of liquid-liquid batch bromination process for the synthesis of 4-bromo-3-methylanisole, a modular microreaction system was constructed by taking microreactor and microbead-packed bed as the major functional microdevice units to intensify the bromination of methylanisole. And in this modular microreaction system, the liquid-liquid heterogeneous continuous bromination of 4-bromo-3-methylanisole was studied. The following optimized conditions were obtained, concentration of Br₂ (x_Br2): 17.5 wt%, molar ratio of Br₂ to methylanisole (n_Br2/n_M): 1.01, initial reaction temperature (T): 0℃, residence time (τ): 0.78 min, with yield of 4-bromo-3-methylanisole more than 98%, and percentage of polybrominated side product less than 1%. Comparing with the conventional batch process, the continuous microreaction technology has obvious advantages. For example, it can change the traditional batch process to a continuous one with a significant increase of productivity (space time yield: 6.5×10⁴ kg/(m³·h)). Besides, since this process is mainly controlled by mass transfer, the modular microreaction system with excellent mass transfer could reduce 50% of polybrominated side product. The study might provide a good foundation for the continuously controllable synthesis of 4-bromo-3-methylanisole in safety.

Key words: microreactor, static mixer, methylanisole, bromination, continuous synthesis, process control

中图分类号:

TQ 530.2499

谢沛, 王凯, 邓建, 骆广生. 模块化微反应系统内溴化间甲基苯甲醚连续合成[J]. 化工学报, 2020, 71(9): 4168-4176.

Pei XIE, Kai WANG, Jian DENG, Guangsheng LUO. Continuous synthesis of 4-bromo-3-methylanisole in modular microreaction system[J]. CIESC Journal, 2020, 71(9): 4168-4176.

图/表 8

图1 间甲基苯甲醚溴化反应网络

Fig.1 Reactions in methylanisole bromination process

图2 实验装置示意图

Fig.2 Experimental set-up of the methylanisole bromination reaction system

图3 微筛孔反应器结构示意图

Fig.3 Detailed structures of micro-sieve micromixer

图4 反应起始温度对产物分布的影响（QBr2-HBr=49.1 ml/min, QM=8.7 ml/min, xBr2=17.5%, xHBr=13.2%, nBr2/nM=1.01, T=0, 5.0, 10.0, 15.0, 20.0, 25.0, 30.0℃, τ=0.78 min, GC测量标准偏差小于0.05%）

Fig.4 Effect of initial reaction temperature on the product distribution

图5 反应物配比对产物分布的影响（QBr2-HBr=49.1 ml/min, QM=8.5 ~ 9.1 ml/min, xBr2=17.5%, xHBr=13.2%, nBr2/nM=0.96, 0.97, 0.99, 1.00, 1.01, 1.02, 1.03, T=0℃, τ=0.78 min, GC测量标准偏差小于0.05%）

Fig.5 Effect of molar ratio of reactants on the product distribution

表1 HBr浓度对产物分布的影响

Table 1 Effect of HBr concentration on the product distribution

项目	1	2	3	4	5
$Q B r 2 - H B r$ / (ml/min)	49.1	49.1	49.1	49.1	49.1
Q_M/ (ml/min)	8.5	9.1	9.4	10.2	11.2
$x B r 2$ / %(mass)	17.5	17.5	17.5	17.5	17.5
x_HBr/ %(mass)	10.0	15.0	20.0	25.0	33.0
$n B r 2$ /n_M	1.01	1.01	1.01	1.01	1.01
T /℃	5.0	5.0	5.0	5.0	5.0
τ/min	0.78	0.78	0.78	0.78	0.78
X_conv /%	97.27	98.28	99.38	98.56	98.06
Y_yield/%	96.48	97.21	97.90	97.24	95.68
Y_BP /%	0.78	1.07	1.48	1.32	2.38

表1 HBr浓度对产物分布的影响

Table 1 Effect of HBr concentration on the product distribution

项目	1	2	3	4	5
$Q B r 2 - H B r$ / (ml/min)	49.1	49.1	49.1	49.1	49.1
Q_M/ (ml/min)	8.5	9.1	9.4	10.2	11.2
$x B r 2$ / %(mass)	17.5	17.5	17.5	17.5	17.5
x_HBr/ %(mass)	10.0	15.0	20.0	25.0	33.0
$n B r 2$ /n_M	1.01	1.01	1.01	1.01	1.01
T /℃	5.0	5.0	5.0	5.0	5.0
τ/min	0.78	0.78	0.78	0.78	0.78
X_conv /%	97.27	98.28	99.38	98.56	98.06
Y_yield/%	96.48	97.21	97.90	97.24	95.68
Y_BP /%	0.78	1.07	1.48	1.32	2.38

表2 Br2浓度对产物分布的影响

Table 2 Effect of Br2 concentration on the product distribution

标号	$Q B r 2 - H B r$ /(ml/min)	Q_M /(ml/min)	$x B r 2$ /%(mass)	x_HBr /%(mass)	$n B r 2$ /n_M	T /℃	τ /min	X_conv/%	Y_yield /%	Y_BP/%
1	49.1	7.7	15.0	15.0	1.01	5.0	0.78	96.82	95.98	0.85
2	49.1	9.1	17.5	15.0	1.01	5.0	0.78	98.28	97.21	1.07
3	49.1	10.3	20.0	15.0	1.01	5.0	0.78	99.45	97.34	2.11
4	49.1	13.8	25.0	15.0	1.01	5.0	0.78	99.69	97.09	2.60

表2 Br2浓度对产物分布的影响

Table 2 Effect of Br2 concentration on the product distribution

标号	$Q B r 2 - H B r$ /(ml/min)	Q_M /(ml/min)	$x B r 2$ /%(mass)	x_HBr /%(mass)	$n B r 2$ /n_M	T /℃	τ /min	X_conv/%	Y_yield /%	Y_BP/%
1	49.1	7.7	15.0	15.0	1.01	5.0	0.78	96.82	95.98	0.85
2	49.1	9.1	17.5	15.0	1.01	5.0	0.78	98.28	97.21	1.07
3	49.1	10.3	20.0	15.0	1.01	5.0	0.78	99.45	97.34	2.11
4	49.1	13.8	25.0	15.0	1.01	5.0	0.78	99.69	97.09	2.60

表3 微反应系统与搅拌釜的溴化结果对比

Table 3 Comparison of bromination results between batch and microreaction system

序号	反应装置	X_conv /%	Y_yield /%	Y_BP/%	Y_STY/(kg/m³·h)
1	搅拌釜	99.56	97.31	2.09	45
2	微反应系统	99.42	98.37	1.05	6.5×10⁴

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