Method for screening multiple reactants and catalyst systems using incremental flow reactor methodology

Abstract

Method for producing multiple chemical reactions and for rapid screening of chemicals, catalysts, process conditions and the like is disclosed. The method includes the steps of providing an array of reactor vessels and reactants; loading each reactor vessel with at least one reactant; and allowing the reactions to proceed for a predetermined time interval. A volume increment is withdrawn from each reactor vessel and a volume increment of at least one reactant is added to each reactor vessel in the array. The steps of volume increment withdrawal and addition are repeated after successive time intervals until the reactions reach a substantially steady state. The loading, withdrawal, and addition steps are performed by liquid or solid handling robots. In one embodiment, the volume increment withdrawal occurs before, after, or contemporaneously with the volume increment addition.

What is claimed is:  
     
         1 . A method for producing multiple chemical reactions and catalytic systems comprising the steps of: 
 (a) providing an array of reactor vessels and reactants;    (b) loading each of the reactor vessels with at least one reactant;    (c) allowing the reactions to proceed for a predetermined time interval;    (d) withdrawing a volume increment from each reactor vessel;    (e) adding a volume increment of at least one reactant to each reactor vessel; and thereafter    (f) repeating steps (c), (d), and (e) until such time the reactions reach a substantially steady state.    
     
     
         2 . The method of  claim 1 , wherein the reactants include phenol and acetone.  
     
     
         3 . The method of  claim 1 , wherein the reactions result in the formation of bisphenol A.  
     
     
         4 . The method of  claim 1 , wherein the volume increment comprises phenol and acetone.  
     
     
         5 . The method of  claim 2 , wherein the reactants further include an acid catalyst.  
     
     
         6 . The method of  claim 2 , wherein the reactants further include a reaction promoter.  
     
     
         7 . The method of  claim 1 , wherein the volume increment withdrawal occurs before, after, or contemporaneously with the volume increment addition.  
     
     
         8 . The method of  claim 1 , wherein the loading, withdrawal, and addition steps are performed by a liquid or solid handling robot.  
     
     
         9 . The method of  claim 1 , further including the step of controlling the size of the volume increments withdrawn and added and the time interval between the additions of the volume increments to obtain a desired reactor residence time.  
     
     
         10 . The method of  claim 1 , wherein the volume increments are withdrawn from the reactor vessels by positioning a probe at a predetermined level in the reactor vessels and withdrawing reactor fluid until no further fluid can be withdrawn at that level .  
     
     
         11 . The method of  claim 1 , wherein the time intervals and the volume increments are selected to obtain a desired space velocity defined by the following equation:  
       wherein: 
 Δt time interval [min];  
 ΔV=volume increment [μL];  
 ρ=density of the volume increment added [g/mL];  
 SV=space velocity [g liquid feed/g resin/hr]; and  
 R=amount of resin [mg].  
 
     
     
         12 . The method of  claim 1 , wherein the withdrawal and addition steps are controlled in the reactor vessels so as to produce sub-interval concentration gradients during the course of the reactions.  
     
     
         13 . The method of  claim 12 , wherein large volume additions followed by sequential withdrawals of smaller volume increments are made to the reactor vessels at predetermined subintervals within the time interval.  
     
     
         14 . The method of  claim 1 , wherein the volume increments withdrawn from the reactor vessels are analyzed for properties of interest.  
     
     
         15 . The method of  claim 1 , wherein the volume increments withdrawn from the reactor vessels are pooled and then analyzed to provide cumulative data.  
     
     
         16 . The method of  claim 1 , wherein after the reactions are allowed to proceed for a predetermined time interval, the volume increments are withdrawn and added simultaneously in each of the reactor vessels.  
     
     
         17 . A method for high throughput screening of chemicals, catalysts, reactants, process conditions and the like comprising the steps of: 
 (a) providing an array of reactor vessels and reactants;    (b) loading each of the reactor vessels with at least one reactant;    (c) allowing the reactions to proceed for a predetermined time interval;    (d) withdrawing a volume increment from each reactor vessel;    (e) adding a volume increment of at least one reactant to each reactor vessel; and thereafter    (f) repeating steps (c), (d), and (e) until such time the reactions reach a substantially steady state.    
     
     
         18 . The method of  claim 17 , further including the step of selecting the predetermined time intervals and the volume increments to obtain a desired space velocity.  
     
     
         19 . The method of  claim 18 , wherein the desired space velocity is defined by the following equation:  
       wherein: 
 Δt=time interval [min];  
 ΔV=volume increment [μL];  
 ρ=density of the volume increment added [g/mL];  
 SV=space velocity [g liquid feed/g resin/hr]; and  
 R=amount of resin [mg].  
 
     
     
         20 . The method of  claim 17 , wherein the reactants include phenol and acetone  
     
     
         21 . The method of  claim 17 , wherein the reactions result in the formation of bisphenol A.  
     
     
         22 . The method of  claim 17 , wherein the volume increment comprises phenol and acetone.  
     
     
         23 . The method of  claim 17 , wherein the reactants further include an acid catalyst.  
     
     
         24 . The method of  claim 17 , wherein the reactants further include a reaction promoter.  
     
     
         25 . The method of  claim 17 , wherein the volume increment withdrawal occurs before, after, or contemporaneously with the volume increment addition.  
     
     
         26 . The method of  claim 17 , wherein the loading, withdrawal, and addition steps are performed by a liquid or solid handling robot.  
     
     
         27 . The method of  claim 17 , further including the step of controlling the size of the volume increments withdrawn and added and the time interval between the additions of the volume increments to obtain a desired reactor residence time.  
     
     
         28 . The method of  claim 17 , wherein the volume increments are withdrawn from the reactor vessels by positioning a probe at a predetermined level in the reactor vessels and withdrawing reactor fluid until no further fluid can be withdrawn at that level .  
     
     
         29 . The method of  claim 17 , wherein the withdrawal and addition steps are controlled in the reactor vessels so as to produce sub-interval concentration gradients during the course of the reactions.  
     
     
         30 . The method of  claim 29 , wherein large volume additions followed by sequential withdrawals of smaller volume increments are made to the reactor vessels at predetermined subintervals within the time interval.  
     
     
         31 . The method of  claim 17 , wherein the volume increments withdrawn from the reactor vessels are analyzed for properties of interest.  
     
     
         32 . The method of  claim 17 , wherein the volume increments withdrawn from the reactor vessels are pooled and then analyzed to provide cumulative data.  
     
     
         33 . The method of  claim 17 , wherein after the reactions are allowed to proceed for a predetermined time interval, the volume increments are withdrawn and added simultaneously in each of the reactor vessels.