Kinetic modeling of dissolution and crystallization of batch - PowerPoint PPT Presentation

East Carolina University Kinetic modeling of dissolution and crystallization of batch reactions with in situ spectroscopic measurements Chun H. Hsieh a , Julien Billeter a , Mary Ellen P. McNally b , Ron M. Hoffman b , Paul J. Gemperline a a Department of Chemistry, East Carolina University, Greenville, NC 27858 b E.I. DuPont de Nemours and Co., Inc., Crop Protection Products and Engineering Technologies, Stine Haskell Research Center, Newark, DE 19711 E-mail: hsiehc07@students.ecu.edu

East Carolina University Outline

East Carolina University Overall project goal – develop monitoring technique for batch processes involving slurries • Extend kinetic modeling approach to a prototypical slurry reaction at DuPont: sulfonylurea coupling reaction for monitoring purposes • Make optical measurements in light-scattering medium • Modify kinetic models to include: • Dissolution of starting material A & flow-in of reagent B • Nucleation and crystallization of product, P • Develop low-theory models for dissolution, nucleation and crystallization • Kinetic models with reagent flow-in impose strict mass balance

East Carolina University Background What is a slurry? • a suspension formed when a quantity of powder is mixed into a liquid in which the solid is only slightly soluble (or insoluble) • contain large amounts of solid and are more viscous and dense than the liquid from which they are formed • Many batch industrial processes use slurries Abebe S. B., Wang X. Z. et al. (2008). Powder Technology 179: 176-183

East Carolina University Background (cont.) What has been done before? • The Gemperline group has developed models for homogenous reactions • chemical reactions in which the reactants are in the solution phase • Kinetic model fitting used for process control • detect processes upset • deduce reasons for processes upset • detect endpoint • forecast changes

East Carolina University Prior work – apparatus setup Batch Titration Reactor

East Carolina University Prior work – apparatus setup Batch Titration Reactor

East Carolina University Typical batch reaction spectra: acetylation of salicylic acid • Experimental details – Circulator system: Julabo F25-HD – Reactor type: 50 mL glass reactor – Initial charge: • 3.0 g salicylic acid • 15 mL acetonitrile • 0.2 mL H 2 SO 4 – Reagent addition • 0.75 mL acetic anhydride @ 0.75 mL/min. • 5 additions @ 25 min intervals UV/Vis spectra � – Calorimeter settings: Equitech CCD • Const temp power comp � mode 3 bounce ATR probe � • Jacket temp: 55 o C Spectra recorded @ 30 s intervals � • Reactor temp: 60 o C

East Carolina University Calorimetry profiles from batch reaction • Composition profiles estimated from SMCR – Fast rate of reaction observed in early steps – Small amt product formed in early steps – Large reaction exotherm in early steps

East Carolina University Kinetic Fitting Algorithm

East Carolina University Kinetic Fitting Algorithm 1. Postulate model 2. Write system of ordinary differential equations 3. Integrate system of simultaneous ODE ’ s 4. Interpolate profiles to match acquisition times Fit profiles to spectra and temperature, R = D ( I – CC -1 ) 5. 6. Adjust model parameters to minimize R using nonlinear least-squares (Levenberg/Marquardt) 7. Repeat steps 3, 4, 5, and 6 until no further improvement is observed in R or maximum number of steps exceeded.

East Carolina University Kinetic Fitting Algorithm 1. Postulate model 2. Write system of ordinary differential equations 3. Integrate system of simultaneous ODE ’ s 4. Interpolate profiles to match acquisition times Fit profiles to spectra and temperature, R = D ( I – CC -1 ) 5. 6. Adjust model parameters to minimize R using nonlinear least-squares (Levenberg/Marquardt) 7. Repeat steps 3, 4, 5, and 6 until no further improvement is observed in R or maximum number of steps exceeded.

East Carolina University Kinetic Fitting Algorithm 1. Postulate model 2. Write system of ordinary differential equations 3. Integrate system of simultaneous ODE ’ s 4. Interpolate profiles to match acquisition times Fit profiles to spectra and temperature, R = D ( I – CC -1 ) 5. 6. Adjust model parameters to minimize R using nonlinear least-squares (Levenberg/Marquardt) 7. Repeat steps 3, 4, 5, and 6 until no further improvement is observed in R or maximum number of steps exceeded.

East Carolina University Kinetic Fitting Algorithm 1. Postulate model 2. Write system of ordinary differential equations 3. Integrate system of simultaneous ODE ’ s 4. Interpolate profiles to match acquisition times Fit profiles to spectra and temperature, R = D ( I – CC -1 ) 5. 6. Adjust model parameters to minimize R using nonlinear least-squares (Levenberg/Marquardt) 7. Repeat steps 3, 4, 5, and 6 until no further improvement is observed in R or maximum number of steps exceeded.

East Carolina University Kinetic Fitting Algorithm 1. Postulate model 2. Write system of ordinary differential equations 3. Integrate system of simultaneous ODE ’ s 4. Interpolate profiles to match acquisition times Fit profiles to spectra and temperature, R = D ( I – CC -1 ) 5. 6. Adjust model parameters to minimize R using nonlinear least-squares (Levenberg/Marquardt) 7. Repeat steps 3, 4, 5, and 6 until no further improvement is observed in R or maximum number of steps exceeded.

East Carolina University Kinetic Fitting Algorithm 1. Postulate model 2. Write system of ordinary differential equations 3. Integrate system of simultaneous ODE ’ s 4. Interpolate profiles to match acquisition times Fit profiles to spectra and temperature, R = D ( I – CC -1 ) 5. 6. Adjust model parameters to minimize R using nonlinear least-squares (Levenberg/Marquardt) 7. Repeat steps 3, 4, 5, and 6 until no further improvement is observed in R or maximum number of steps exceeded.

East Carolina University Kinetic Fitting Algorithm 1. Postulate model 2. Write system of ordinary differential equations 3. Integrate system of simultaneous ODE ’ s 4. Interpolate profiles to match acquisition times Fit profiles to spectra and temperature, R = D ( I – CC -1 ) 5. 6. Adjust model parameters to minimize R using nonlinear least-squares (Levenberg/Marquardt) 7. Repeat steps 3, 4, 5, and 6 until no further improvement is observed in R or maximum number of steps exceeded.

East Carolina University The reactions and model parameters k 1 k 2 AA + SA I ASA + HA k 3 AA + W 2 HA k 4 AA + ASA ASAA + HA SA: salicylic acid Reactor is filled with SA and AA: acetic anhydride AA is injected in the reactor I: reactive intermediate ASA: acetyl salicylic acid ASAA: acetylsalicylic anhydride Estimated model parameters: W: water C W k 1 , k 2 , k 3 , k 4 HA: acetic acid

East Carolina University Isothermal model with flow-in reagents = r k C C dC C 1 1 SA AA = − − W W r F 3 AA = r k C dt V 2 2 I dC C = r k C C ASAA = − ASAA r F 3 3 W AA 4 AA dt V = r k C C 4 4 ASA AA dC C HA = + + − HA r 2 r r F 2 3 4 AA dt V − dC C C = − − − + AA AAin AA r r r F dV 1 3 4 AA = F dt V AA dt dC C = − − I I r r F 1 2 AA dt V conc x Est. pure spectra Est. dC C SA = − − SA Batch 1 r F = 1 AA spectra dt V

East Carolina University Kinetic fitting – details for step 5 5. Fit kinetic profiles to measured spectra using linear least- squares

East Carolina University Kinetic fitting – details for step 5 5. Fit kinetic profiles to measured spectra using linear least- squares

East Carolina University Motivation - application to a DuPont batch slurry process • Develop a kinetic model for a DuPont’s sulfonylurea coupling reaction (heterogeneous reaction) for monitoring purposes • Modify kinetic models to include: Dissolution of starting material A & flow-in of reagent B • Nucleation and crystallization of product, P • Make optical measurements in light-scattering medium • • Kinetic models with flow-in impose strict mass balance • Develop low-theory models for dissolution, nucleation and crystallization • avoid high-theory and medium-theory models (e.g. population balance equation)

East Carolina University High-theory model: population balance equations − B = I J A exp[ ] Nucleation (B) NI I 2 β (ln ) − B = II J A S exp[ ] NII II β ln Φ dL M k Crystal Growth (G) j = = s s c η − G ( C C *) r Φ dt 3 d s v Population Balance ∂ ψ ∂ ψ 1 V G ( ) ( ) + = + δ − J J L L * Equation NI NII ∂ ∂ V t L Blandin, A.; Mangin, D.; Nallet, V.; Klein, J.; Bossoutrot, J. Chemical Engineering Journal , 2001 , 81, 91-100