Synthesis Process Of1-Azetidinesulfonicacid In A Packed-bed Oscillatory Flow Reactor

Aztreonam is a β-monobactam antibiotic, whose synthetic process usually starts with L-threonine as a raw material and goes through esterification, ammonolysis, amino protection reaction, hydroxy formylation reaction, sulfonation, cyclization, amino pro-tecting group eliminating reaction, amidation reaction and tertbutyl eliminating reac-tion between main ring of aztreonam and TAEM (2-Mercaptoben zothiazol-yl-(Z)-(2-aminothiazol-4-yl)-2-(tert-butoxycarbonyl)isopropoxyiminoacetate). Specif-ically, amino deprotection reaction is to hydrogenolysize the Carboben-zoxy-1-Azetidinesulfonicacid(CA), which is where the main cost lies in aztreonam synthesizing process and usually adopts batch stirred reactor with powdered Pd/C(palladium-carbon) catalyst. In order to increase productivity, ensure product quality and stability and reduce production cost, we planned to design a optimized continuous industrial production process for it, which is also the research objective of this article. We studied kinetics of supported beaded Pd/C catalyst. Considering char-acteristics of this gas-liquid-solid-phase reaction, using a Packed-bed Oscillatory Flow Reactor(POFR) to carry on amino protecting group deprotection reaction so as to in-tensify interphase transfer rate and catalyst surface renewal rate and realize the plug-flow continuous reaction process. Main work is as below:To select or design the appropriate type of reactor is the critical point in designing and optimizing continuous process and it requires sufficient understanding of the reac-tion’s characteristics. In this article, by using a self-made external circulation gradient-less reactor, we investigated how reactants concentrations changed at different reaction temperatures and hydrogen pressures and studied the effects brought by hydrogen’s solubility in reaction solution. We discovered that an increase in reaction temperature and hydrogen pressure accelerates reaction rate. A reaction kinetic model was success-fully built up, in which the reaction order for the reactant of CA is1and for hydrogen it’s0.28, and reaction activation is39.062kJ/mol. After checking, we found that the mean relative error of predicted results from kinetic model and actual data from ex- periments is6.4%, which is acceptable for engineering designing.The catalyst used in this reaction is noble metal palladium, whose lifetime is the crucial factor of cost of the process. We studied the stability of the catalyst with ex-periments and found that catalyst activity decreasement was not apparent after reacting continuously for96hours, which meant the above catalyst had an excellent stability.This is a gas-liquid-solid-phase reaction system and a novel POFR was used as the continuous reaction equipment. In a self-made POFR with water as the mobile phase, we studied the flow pattern at different oscillating frequencies and amplitudes and on-line detected the Residence Time Distribution(RTD) under various oscillating conditions. Afterwards, Axial Diffusion Model was used to describe the flow pattern in the above POFR and values of model parameters were determined at last. We studied the impact of oscillating frequency and amplitude on such model parameters and com-pared the flow pattern with that without oscillation. Results showed that at different oscillating amplitudes, the way values of Pe (Peclet) varied by oscillation frequency was different. At lower oscillating amplitudes, Pe increased by oscillating frequency; while at higher oscillating amplitudes, Pe decreased by oscillating frequency. Com-pared to the situation without oscillation, all values of Pe increased when oscillation was imposed. A dimensionless parameter named λ(λ=amplitude x/catalyst diameter d) was introduced for fitting calculation and the relational expression between axial dis-persion coefficient Ez and oscillating frequency at different values of λ was attained. Furthermore, we carried on the reaction in a PBOFR and studied the impact of oscilla-tion on the reaction’s transfer process. Results showed that the conversion increased when imposing proper oscillation. What’s more, we introduced mass transfer en-hancement factor E to quantitatively describe the impact of oscillation on the reaction. Finally, we realized the continuous hydrogenolysis process of CA in the POFR.