2-氯-5-氯甲基吡啶合成工艺的改进
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摘要
2-氯-5-氯甲基吡啶是重要的农药和医药中间体,同时,还可衍生为2-氯-5-氨甲基吡啶,该化合物也是重要的农药和医药中间体。
本文针对2-氯-5-氯甲基吡啶工业生产中存在的环合反应收率低,污染大的问题,在预实验的基础上,优化环合反应,改进精制工艺,使反应及分离过程中不用甲苯,采用结晶法提纯目的产物,从而简化了工艺过程,降低了生产成本。同时,对2-氯-5-氯甲基吡啶工业品进行多次重结晶以获得标准品,并用差热扫描仪(DSC)测定2-氯-5-氯甲基吡啶的熔融焓为-15294.42J/mol。依据工厂生产实际的要求,对2-氯-5-氯甲基吡啶在水和有机溶剂中的溶解度进行了测定,并筛选出了合适的溶剂用于分离提纯2-氯-5-氯甲基吡啶。
本文采用单因素实验法考察了影响2-氯-5-氯甲基吡啶环合反应及其分离提纯的因素,直接采用2-氯-2-氯甲基-4-氰基丁醛-N,N-二甲基甲酰胺溶液为原料,不再添加其他溶剂,优化出环合反应的较佳工艺条件：n(2-氯-2-氯甲基-4-氰基丁醛)：n(三氯氧磷)=1：0.6,反应温度90℃,反应时间8h。在此工艺条件下,2-氯-5-氯甲基吡啶收率达77.91%。同时,开发出2-氯-5-氯甲基吡啶结晶提纯工艺：用所筛选的溶剂搅拌降温结晶,溶剂用量5 mL/(g反应液),结晶温度3～6℃,结晶时间4h。所得目的产物2-氯-5-氯甲基吡啶纯度>90%,提纯率>83%,可达到工业生产要求,避免了精馏工艺造成的2-氯-5-氯甲基吡啶分解。
为了筛选结晶所用溶剂,本文用带激光监视系统可控升温速率的溶解度测定装置,测定2-氯-5-氯甲基吡啶在水以及甲醇、乙醇、乙酸乙酯、丙酮、氯仿和甲苯等7个二元体系的固液相平衡数据。通过对标准物系苯甲酸-水体系的测定,对该装置的可靠性进行了验证,其测量值与文献值相比,相对误差小于2%。用变温溶解法测定了温度范围从275.85K到309.15K之间2-氯-5-氯甲基吡啶在水以及有机溶剂等7个二元体系共89组溶解度数据,所测体系的溶解度数据均未见文献报道,为化工数据库增添了新的内容。
本文采用理想溶液方程,Apelblat方程和Wilson方程关联了常压下2-氯-5-氯甲基吡啶在水及有机溶剂中二元体系的固液相平衡数据,取得了较好的关联结果,并得到了相关参数。理想溶液方程对水、甲醇、乙醇、乙酸乙酯、丙酮、氯仿和甲苯关联平均相对误差最大为1.22%,Apelblat方程关联平均相对误差最大为1.06%,wilson方程关联平均相对误差最大为3.65%。计算结果与实验结果相比较,总体相对误差较小,说明本文所用方程在所研究的温度范围和浓度范围内适用。
2-Chloro-5-chloromethylpyridine is the crucial intermediate of pesticide and medicine. And another crucial intermediate of pesticide and medicine,2-Chloro-5-amino methylpyridine can be also derivated from it.
The innovation of technology synthesizing 2-Chloro-5-chloromethylpyridine is a subject of which aims at working out the problem of low yield and much pollution from the current cyclization technology. In this paper, the cyclization reaction has been optimized, and the method of crystallization was used for purifying the aim product on the basis of preliminary experiments. So the technology is simplified for synthesizing 2-Chloro-5-chloromethylpyridine and cut down the operating costs. The pure 2-Chloro-5-chloromethylpyridine can be obtained by repetitious recrystallization. The melting enthalpy is observed to be-15294.42 J/mol of 2-Chloro-5-chloromethylpyridine by DSC scan. At the same time, the saturate characteristics of 2-Chloro-5-chloromethylpyridine were detemined in water and in some organic solvents, and the proper solvent was be taken as a choice from among several. They provide the thermodynamics basic data for industrial produce 2-Chloro-5-chloromethylpyridine.
In this paper, single-factor test, which influence the 2-chloro-5-chloromethyl pyridine cyclization reaction,separation and purification of the factors that directly using 2-chloro-2-chloromethyl-4-cyanobutyraldehyde-N,N-Dimethyl formamide solution as raw material, not to add other solvents, optimization of the cyclization reaction of the better conditions are n(2-chloro-2-chloromethyl-4-cyanobutyral dehyde):n(phosphorus oxychloride)= 1:0.6, the temperature of cyclization reation is 90℃, and the reaction time is 8 hours. At this procedure, the yield of 2-Chloro-5-chloromethylpyridine is observed to be 77.91%. At the control of stirring, the solvent is added at the dosage of 5mL per gram reaction solution, and the crystallization temperature is 3～6℃. The crystallization procedure demands 4 hours. The purity of 2-Chloro-5-chloromethylpyridine exceed 90%, and the purification rate exceeds 83%. The technics meets the needs of industry production becauce of avoiding the decomposing of 2-Chloro-5-chloromethylpyridine on the basic of distillation technics.
The solubility data of the binary systems of 2-Chloro-5-chloromethylpyridine in water, methanol, ethanol, ethyl acetate, acetone,trichloromethane and toluene are measured at the temperature range of 275.85 K to 309.15K by using laser detection technique at atmospheric pressure, respectively. To testify the uncertainty of the measurement, a comparison with the literature values for the solubility of benzoic acid in water was made. It can be seen that the relative deviation in the mole fraction solubility is less than 2%. These data fill up the blank of the solid-liquid equilibrium data of 2-Chloro-5-chloromethylpyridine.
The solubility model of the Ideal solution equation, Apelblat eqution and Wilson equation are proposed, and calculated solubilities by the model show good agreement with experimental data. At the same time, the related parameters are obtained in these models. The maximum error of Ideal eqution, Apelblat eqution and Wilson eqution were 1.22%,1.06% and 3.65%, respectively. The overall error is small by comparing between calculated results and experiment results. So it is appropriate that the solubility models are applied for relationship the solubility with temperature at the experimental range of temperature and concentration.
本文针对2-氯-5-氯甲基吡啶工业生产中存在的环合反应收率低,污染大的问题,在预实验的基础上,优化环合反应,改进精制工艺,使反应及分离过程中不用甲苯,采用结晶法提纯目的产物,从而简化了工艺过程,降低了生产成本。同时,对2-氯-5-氯甲基吡啶工业品进行多次重结晶以获得标准品,并用差热扫描仪(DSC)测定2-氯-5-氯甲基吡啶的熔融焓为-15294.42J/mol。依据工厂生产实际的要求,对2-氯-5-氯甲基吡啶在水和有机溶剂中的溶解度进行了测定,并筛选出了合适的溶剂用于分离提纯2-氯-5-氯甲基吡啶。
本文采用单因素实验法考察了影响2-氯-5-氯甲基吡啶环合反应及其分离提纯的因素,直接采用2-氯-2-氯甲基-4-氰基丁醛-N,N-二甲基甲酰胺溶液为原料,不再添加其他溶剂,优化出环合反应的较佳工艺条件：n(2-氯-2-氯甲基-4-氰基丁醛)：n(三氯氧磷)=1：0.6,反应温度90℃,反应时间8h。在此工艺条件下,2-氯-5-氯甲基吡啶收率达77.91%。同时,开发出2-氯-5-氯甲基吡啶结晶提纯工艺：用所筛选的溶剂搅拌降温结晶,溶剂用量5 mL/(g反应液),结晶温度3～6℃,结晶时间4h。所得目的产物2-氯-5-氯甲基吡啶纯度>90%,提纯率>83%,可达到工业生产要求,避免了精馏工艺造成的2-氯-5-氯甲基吡啶分解。
为了筛选结晶所用溶剂,本文用带激光监视系统可控升温速率的溶解度测定装置,测定2-氯-5-氯甲基吡啶在水以及甲醇、乙醇、乙酸乙酯、丙酮、氯仿和甲苯等7个二元体系的固液相平衡数据。通过对标准物系苯甲酸-水体系的测定,对该装置的可靠性进行了验证,其测量值与文献值相比,相对误差小于2%。用变温溶解法测定了温度范围从275.85K到309.15K之间2-氯-5-氯甲基吡啶在水以及有机溶剂等7个二元体系共89组溶解度数据,所测体系的溶解度数据均未见文献报道,为化工数据库增添了新的内容。
本文采用理想溶液方程,Apelblat方程和Wilson方程关联了常压下2-氯-5-氯甲基吡啶在水及有机溶剂中二元体系的固液相平衡数据,取得了较好的关联结果,并得到了相关参数。理想溶液方程对水、甲醇、乙醇、乙酸乙酯、丙酮、氯仿和甲苯关联平均相对误差最大为1.22%,Apelblat方程关联平均相对误差最大为1.06%,wilson方程关联平均相对误差最大为3.65%。计算结果与实验结果相比较,总体相对误差较小,说明本文所用方程在所研究的温度范围和浓度范围内适用。
2-Chloro-5-chloromethylpyridine is the crucial intermediate of pesticide and medicine. And another crucial intermediate of pesticide and medicine,2-Chloro-5-amino methylpyridine can be also derivated from it.
The innovation of technology synthesizing 2-Chloro-5-chloromethylpyridine is a subject of which aims at working out the problem of low yield and much pollution from the current cyclization technology. In this paper, the cyclization reaction has been optimized, and the method of crystallization was used for purifying the aim product on the basis of preliminary experiments. So the technology is simplified for synthesizing 2-Chloro-5-chloromethylpyridine and cut down the operating costs. The pure 2-Chloro-5-chloromethylpyridine can be obtained by repetitious recrystallization. The melting enthalpy is observed to be-15294.42 J/mol of 2-Chloro-5-chloromethylpyridine by DSC scan. At the same time, the saturate characteristics of 2-Chloro-5-chloromethylpyridine were detemined in water and in some organic solvents, and the proper solvent was be taken as a choice from among several. They provide the thermodynamics basic data for industrial produce 2-Chloro-5-chloromethylpyridine.
In this paper, single-factor test, which influence the 2-chloro-5-chloromethyl pyridine cyclization reaction,separation and purification of the factors that directly using 2-chloro-2-chloromethyl-4-cyanobutyraldehyde-N,N-Dimethyl formamide solution as raw material, not to add other solvents, optimization of the cyclization reaction of the better conditions are n(2-chloro-2-chloromethyl-4-cyanobutyral dehyde):n(phosphorus oxychloride)= 1:0.6, the temperature of cyclization reation is 90℃, and the reaction time is 8 hours. At this procedure, the yield of 2-Chloro-5-chloromethylpyridine is observed to be 77.91%. At the control of stirring, the solvent is added at the dosage of 5mL per gram reaction solution, and the crystallization temperature is 3～6℃. The crystallization procedure demands 4 hours. The purity of 2-Chloro-5-chloromethylpyridine exceed 90%, and the purification rate exceeds 83%. The technics meets the needs of industry production becauce of avoiding the decomposing of 2-Chloro-5-chloromethylpyridine on the basic of distillation technics.
The solubility data of the binary systems of 2-Chloro-5-chloromethylpyridine in water, methanol, ethanol, ethyl acetate, acetone,trichloromethane and toluene are measured at the temperature range of 275.85 K to 309.15K by using laser detection technique at atmospheric pressure, respectively. To testify the uncertainty of the measurement, a comparison with the literature values for the solubility of benzoic acid in water was made. It can be seen that the relative deviation in the mole fraction solubility is less than 2%. These data fill up the blank of the solid-liquid equilibrium data of 2-Chloro-5-chloromethylpyridine.
The solubility model of the Ideal solution equation, Apelblat eqution and Wilson equation are proposed, and calculated solubilities by the model show good agreement with experimental data. At the same time, the related parameters are obtained in these models. The maximum error of Ideal eqution, Apelblat eqution and Wilson eqution were 1.22%,1.06% and 3.65%, respectively. The overall error is small by comparing between calculated results and experiment results. So it is appropriate that the solubility models are applied for relationship the solubility with temperature at the experimental range of temperature and concentration.
引文
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