Process Intensification in the Customized Flow Reactors

Abstract

The development and intensification of flow reactors are emerging as a new niche area in the pharmaceutical process development. However, development without adequate knowledge of chemistry, kinetics, mass and heat transfer, equipment design, residence time and residence time distribution (RTD) aspects could be difficult to realize the true potential of flow processing development. Understanding these aspects would enable the experimenter to explore options, troubleshoot, and find insights into a wide array of possibilities for continuous flow chemistry development and scaleup. The study provides a systematic approach for flow process development, insights to characterize the equipment, optimize the conditions, and derive meaningful conclusions. The results are presented through appropriate tables and charts to understand the concepts and apply them for various processes. As a case study, a well-known saponification reaction was subjected to represent the performance of the batch versus the flow process (packed bed reactor and tubular reactor) and listed advantages.

1. Introduction

1.1 Highlights

• Designing, development, and characterization of continuous flow reactors (tubular and packed bed reactor) through RTD studies.

• Overview of dimensionless numbers and their influence on these flow reactors

• Effect of kinetic parameters over batch and flow systems

• Estimation of various thermodynamic properties to assist equipment design

• Process intensification of continuous flow reactors to achieve maximum performance.

• Validation of these reactors using well know reaction system and listing out advantages of flow over batch processes.

Continuous production techniques have been used by the chemical industry for a long time, but it is only recently that flow equipment has become available for the use of the laboratory scale, especially in the pharmaceutical industry. This means that flow processes established in the lab could be readily transferred to the production facilities and scaled for commercial use, without substantially altering the reaction conditions [1, 2, 3]. The flow processes are gaining high visibility across pharmaceutical industries for varied reasons [4]. One reason could be predominately the economics of running the batch processes verses the flow process. At the onset, the flow processes are well established in the manufacturing of commodity chemicals, meanwhile, the batch processes are highly acquainted in the pharmaceutical industries. In the advent, the flow processes offer wide advantages such as effective heat and mass transfer, superior inherent safety, flexibility, reproducibility, energy efficiency, high reactor throughput, fast and effective mixing, low footprint, in-line automation, and low operating cost [5].

Flow processing has demonstrated chemical production safer, more reproducible, and scalable while offering reduced cost and low environmental impact. Flow processes are more energy-efficient, with precise control over reaction conditions leading to less waste and environmental impact and serving green chemistry principles [6].

By way of example, for every kilogram of a fine chemical produced by the pharmaceutical industry, 5–100 times that amount of chemical waste is being generated [7]. This unacceptable inefficiency with the present state-of-the-art, large scale batch production of chemicals is driving the adoption of resource-efficient flow chemistry alternatives as innovative solutions for chemical manufacturing.

Developments are at a high pace in transforming the batch chemistries to flow processes at the academic level and there is a quite demand building up across industries. In recent years, flow chemistry has become a viable alternative to traditional batch chemistry, with a six-fold increase [6] in the publications featuring micro and meso reactors. The literature which supports the transformations was more in running the experiments without the engineering concepts being discussed such as kinetics, mixing, dispersion, and residence time distributions. On the other side, there have been numerous companies launching flow process development skids for quick and easy development strategies without insight on the reaction or its suitability. An effort towards understanding these concepts become decisive.

Flow reactors for continuous flow processing are typically tubular, packed bed, or microfluidic chip-based systems, where reagents are introduced at different points into the tube in a continuous stream [8]. Because of the small dimension of the tubes and built-in automation, well-defined temperature, pressure, and reaction times are achieved thereby achieving desired product profiles. Initial capital outlay is reduced, compared to traditional batch reactors, and scale-ups could be achieved by running identical parallel channels, making flow chemistry a viable manufacturing approach for small and niche manufacturers.

The characterization of the reactor such as flow patterns becomes essential to decide the performance of these reactor types. There are specific methods available in the literature to characterize the flow reactors, whether it is plug flow, CSTR (Continuous stirred tank reactors), fluidized bed reactor, or packed bed reactor [9, 10, 11]. Generally, there is two class of reactors, which are completely mixed or completely plug flow reactors. The residence time distribution (RTD) studies [12, 13, 14, 15] were performed to characterize [16, 17, 18, 19] the reactor types and to estimate the deviation from the ideal behavior of the reactor under the flow conditions. All the real reactors fall, somewhere between mixed and plug flow [12, 20], the reason could be due to stagnation, recycling of the fluid, channeling of fluid, the difference in the temperature, inadequate mixing with the reactant streams and axial dispersion patterns [13].

As a first approximation, one could establish a model around each reactor to prove the performance using the characteristic information defined in the literature [21]. In the real scenario, we could realize the ineffective contacting, mixing, and lowering in the performance than the ideal case [18, 22]. The RTD is characteristic information to estimate the degree of mixing and opportunities to improve the same through the design of the reactor [12]. Nevertheless, the RTD studies provide significant information around the gaps and opportunities to improve the process from an equipment perspective [22, 23, 24]. In general, the shortfalls could be around the channeling, recycling of the fluid, stagnation, and dead zones within the reactor [9].

Various dimensionless parameters were discussed in the literature to support the studies and to develop correlation to understand the performance behavior of these reactors [22, 25, 26, 27].

In the present study, customized plug flow and packed bed reactors were designed and fabricated on an appropriate scale. The reactors were characterized through detailed RTD studies. The characteristic plots are used to estimate the behavior of the flow reactor. Well-studied saponification of ethyl acetate in the presence of sodium hydroxide was considered for validating these reactors and demonstrating the advantages of flow processes over the batch process. The hydrolysis of ethyl acetate was essentially an irreversible second-order reaction, in which the sodium acetate and ethyl alcohol were formed as products. In the literature, the emphasis was given to reaction kinetics and mechanism of the reaction than process intensification using various reactor types and their importance. The information around detailed process intensification studies is very nominal and not available in the open literature to the best of authors’ knowledge.

2. Materials and methods

All the chemicals were sourced from Sigma Aldrich, Bengaluru, and used for the complete experimental work. The stock solutions were prepared freshly every time using Milli-Q water before conducting any experiments, to avoid data inconsistency.

Conductivity meter (Eutech, CyberScan CON 510, supplied by ComBiotech, Bengaluru) was used to analyze the concentration of sodium hydroxide solution. The customized reactors were built using materials sourced from ComBiotech-Bengaluru, Huber-Germany, and Swagelok-India respectively. We have investigated the saponification reaction as a general procedure for the process intensification in these customized flow reactors.

3. Experimental section

3.1 Calibration curve for the concentration analysis

Calibration curve was established using freshly prepared stock solution of sodium hydroxide of various concentrations such as 40, 80, 400, 800, 2000–4000 mg/L. The conductivity of each stock solution was measured using a conductivity meter. The values of conductance of each sample were plotted against the concentration of sodium hydroxide, which was used as a reference for all the experiments to find the unknown concentration of experimental samples.

3.2 Equipment setup and experimental procedure

3.2.1 Batch reactor setup

A schematic representation of the batch reactor setup is shown in Figure 1. All the batch experiments were performed in a jacketed reactor setup equipped with a 250 mL reactor fitted with a coiled condenser. The pitch blade turbine was used as an agitator for conducting experiments. The head of the reactor had 5 ports, of which one was used for a temperature probe (T), other for the agitator shaft, a third for condenser along with nitrogen vent, fourth was used for inserting conductivity probe (C), and the fifth one for dosing reagents.

Figure 1.

Schematic and actual image of the batch reactor.

3.2.2 Tubular reactor setup (type 1)

The tubular flow reactor was fabricated using perfluroalcoxy alkane (PFA) tubes with internal diameter 1.58 and 3.175 mm (supplied by Swagelok) coiled with the definite volume rolled into a disc form, connected with a T- joint and a static mixer (supplied by ColeParmer) and immersed into a bath circulator. Two pumps A and B (QG50, supplied by FMI, Inc) were used to pump the reaction mixture at a definite flow rate. The open bath circulator (supplied by Huber, Germany) was used to control the temperature of the flow reactor. The schematic and actual image of the experimental setup is shown in Figure 2.

Figure 2.

Schematic and actual image of the tubular reactor.

3.2.3 Packed bed reactor (type 2)

The packed bed reactor (fabricated through ComBiotech, Bengaluru) was made up of glass, filled with glass beads of 2 mm thickness with a sintered disc at the bottom. The diameter and the length of the reactor are 24 and 240 mm respectively. The volume of the column is 105 mL, with packing is around 56 mL. The PFA tubes were used for all fluid connections. The reactor jacket inlet and outlet (12 mm threaded ends) were connected to a bath circulator (supplied by Huber, Germany), to maintain the required temperature of the reactor. The reactor inlet was connected to two pumps (QG50, Fluid metering, Inc) to pump the reaction mixture along with a static mixer in-line to the reactor and a k-type thermocouple was placed in the packed bed to monitor the internal bed temperature. The schematic and actual image of the experimental setup is shown in Figure 3. The output of the reactor was connected to a collection vessel. The samples were drawn from the collection tube and analyzed through a conductivity meter. The reactions were performed both in an upward and downward flow to study the process variations in detail.

Figure 3.

Schematic and actual image of the packed bed reactor.

3.2.4 Tubular reactor setup (type 3)

The tubular reactor was fabricated using PFA tubes with a diameter 1.58 mm (supplied by Swagelok) coiled with the definite volume rolled into a disc form, connected with a T- joint and a static mixer (supplied by ColeParmer) and immersed into a temperature-controlled Sonicator bath. Two pumps A and B were used to pump the reaction mixture at a definite flow rate. The Sonicator bath (supplied by ComBiotech, Bengaluru) was used to control the temperature of the flow reactor with a fixed sonication frequency. The output of the reactor was connected to a collection vessel.

3.2.5 RTD studies to characterize the reactor types

The flow reactors were characterized through RTD studies using sodium hydroxide (NaOH) as tracer input to develop characteristic curves such as E, F, and C curves and other relevant parameters. For better visual detection and quantification of flow patterns of the tracer element, Rhodamine B (synthetic dye) was also used. The concentration of the tracer was around 0.1 N NaOH, prepared through dissolving 4 grams of NaOH in 1 liter of Milli-Q water.

Two methods of injection were used, such as pulse and step inputs during the experiments. The pulse input injection was done by the construction of a T-joint and an injection port, where a 10 mL tracer was injected. For the step input, the inlet of the pump was swapped from inline water flow into the beaker containing the tracer solution at time t = 0.

A constant flow rate of 15.8 mL/min was maintained for all the trials performed. The tracer concentration at the exit was measured by a conductivity meter as a function of time and plotted all the characteristic curves. The concentration of tracer measured was in terms of milli siemens per centimeter.

3.3 Estimation of reaction kinetics and relevant parameters

3.4 Reaction scheme

The saponification reaction under basic condition is represented by the following reaction scheme. The rate equation for this reaction could be represented as (Figure 4) [28].

Figure 4.

Reaction scheme of saponification reaction.

$$-{\mathrm{r}}_{\mathrm{a}}=-{\mathrm{r}}_{\text{NaOH}}=\mathrm{k}{\mathrm{C}}_{\text{NaOH}}{\mathrm{C}}_{\text{Ethylacetate}}.$$

The hydrolysis of ethyl acetate was essentially an irreversible second-order reaction, in which the sodium acetate and ethyl alcohol were formed as products. The reaction was represented as ethyl acetate proceeds with a direct attack of the nucleophile on the carbon atom of ethyl acetate [25]. In another study [16], found transition complex formation was a result of nucleophilic interaction of water molecule, where hydroxide ions generally assist the complex formation. The reaction investigation was conducted through a series of experiments in a tubular, packed, and batch reactor and analyzed. The experimental data were fitted with a second-order model at the end to compare the performance [17].

4. Results and discussion

A calibration curve was established using a freshly prepared stock solution of sodium hydroxide of various concentrations. For reaction samples, at time zero, the conductivity values were measured before the reaction was initiated to get the initial concentration of the solutions and then measured at each time interval in batch. Similarly, the samples from the exit of the flow reactors are measured to obtain the amount of sodium hydroxide reacted with ethyl acetate solution and were then correlated by the equation obtained by the slope of the calibration chart (Figure 5).

Figure 5.

Calibration chart of standard concentration of NaOH and its conductivity values.

4.1 RTD studies

The experiments were performed as per the procedure [22] for reactor type 1 and 2. A constant flow rate of 15.8 mL/min was set for all the tracer studies. The pulse input injection was done by the construction of a T-joint and an injection port, where a 10 mL tracer was used for every injection. For step input studies the input to the pump was transferred from inline water flow into the beaker containing the tracer solution. As we proceeded with the characterization of the flow reactors, the pulse method of injection was found to generate inaccurate and inconsistent data. So, final quantification experiments were conducted only with step inputs. Apart from sodium hydroxide, Rhodamine B was also used for the detection of flow patterns and presented data (Table 1).

Type of reactor	Mean residence time, tm, s	Variance, σ^2, s^2	Skewness, S, s^3	Dispersion number, D/uL	Reynolds number, Re	Bodenstein number, B0	Damköhler number, Da
Tubular reactor (type 1)	543.19	124,890	7.70E+07	0.00068	47.58	1453	0.163
Packed bed reactor (type 2)	676.8	244,385	1.37E+08	0.0122	0.215	81.35	1.57

Table 1.

Experimental residence time distribution parameters for reactor type 1 and 2.

The C, F, and E curves were drawn for each of the reactors set up. Figures 6–8 represents curves for the tubular reactor of type 1. We observed an F(t) of 3.5 minutes was 0.12, 5.5 minutes was 0.35, which means 12% and 35% of the molecules spent less the 3.5 and 5.5 minutes respectively in the reactor. Also, we could derive 80% of the molecules spend 13 minutes or less in the reactor and around 20% of the molecules spend longer than 13 min in the reactor. We find that around 54% of the material leaving the reactor spends between 3.5 and 5.5 minutes. The long-time portion in this is between 21 and 36 minutes, which accounts for 3% of the material being spent in the reactor.

Figure 6.

F-curve, change in concentration (C/C₀) with respect to time.

Figure 7.

C-curve, tracer concentration with respect to time.

Figure 8.

E-curve, tracer concentration with respect to time.

Similarly, the C, F, and E curves were developed for the packed bed reactor (type 2). Figures 9–11 represent curves for the type 2 reactor setup. Here we observed an F(t) of 4 minutes was 0.21, 6 minutes was 0.35, which means 21% and 35% of the molecules spent less the 4 and 6 minutes respectively in the reactor. Also, we could derive 81% of the molecules spend 10 minutes or less in the reactor and around 20% of the molecules spend longer than 14 min in the reactor. We find that around 42% of the material leaving the reactor spends between 4 to 6 minutes. The long-time portion in this is between 18 and 24 minutes, which accounts for 5.5% of the material being spent in the reactor. So, the type 1 reactor behavior is better in comparison with type 2 reactor concerning the performance and behavior close to the ideality. The performance curves for type 3 reactor are similar to the type 1 reactor, as both are tubular flow reactors. Additional experiments for type 2 reactor were performed under gravity and against gravity conditions to compare the behavior of the two methods. The trend clearly shows the deviation is quite large with gravity conditions due to by-passing, and channeling effects. To improve the performance, one could use running the packed columns against gravity with an add-on sintered plate at the top of the reactor which could change the dynamics and distributions of flow across the packed bed.

Figure 9.

F-curve, change in concentration (C/C₀) with respect to time.

Figure 10.

C-curve, tracer concentration with respect to time.

Figure 11.

E-curve, tracer concentration with respect to time.

The mean residence time for type 1 and 2 reactors were found to be 9.05 and 11.28 minutes, where the average residence time was around 1.26 and 3.05 minutes respectively. This indicates there is a dispersion all along the fluid path and across boundaries.

The variance (${\sigma }^2$) is an indication of the “spread” of the distribution; the greater the value, the higher the distribution across the path for the reactor. In our case, it was around 124,890 and 244,385 s², which clearly states that spread is almost twice in a packed bed reactor in comparison with the tubular reactor. The skewness factor measures the extent that a distribution is skewed in one direction or another about the mean. In general, all the three parameters mentioned above are essential to characterize the distribution and are enough to understand. A skewness factor(S) of around 7.70E+07 and 1.37E+08 sec³ was found for type 1 and type 2 reactors respectively.

The dispersion numbers were also estimated a trial and error basis. First assume a small dispersion, say σ²/t_m² is equal to 2D/uL and equate to get the appropriate dispersion. In our case, we found 0.00068 and 0.0122 for type 1 and type 2 reactors respectively, which clearly states a smaller dispersion in the case of type 1 and reasonable large dispersion in type 2 reactor from ideal plug flow behavior. Since the dispersion number varies along the length of the reactor and the mean residence time is higher than that of the theoretical residence time, the reactors are classified as closed systems. The changes in the packing materials used in the packed column had a significant effect on the flow pattern. To further simplify the plug flow behavior, the ratio of the length of the reactor and their effective diameters revealed to be higher than 50 for all the systems.

The Peclet number (Pe) was estimated and found to be 1470 and 81 for type 1 and type 2 reactors. The behavior of reactor type 1 is more or like the plug flow and reactor type 2 is behaving far from ideal conditions.

The Reynolds number (Re) is dimensionless describes the ratio of inertial to viscous forces. The regime for flow through a packed bed may be identified by the packed bed Re. The type 1 reactor falls under the transitional region and type 2 reactor falls under the laminar region.

Bodenstein number (B₀) was estimated and found to be 1452 and 81 for type 1 and type 2 reactor respectively. It could be concluded that both the reactors have varying degrees of back mixing, however, the variation in the flow velocity could be used to control or adjust B₀ for the desired condition.

Similarly, the Damköhler number (Da) was estimated to realize the mass transfer rates using the standard equation available in the literature [19]. A 0.163 and 1.57 were found for type 1 and 2 reactors, which signifies diffusion occurs much faster than the reaction, thus diffusion reaches equilibrium well before the reaction is at equilibrium for type 1 reactor and diffusion-limited system for type 2 reactor.

4.2 Estimation of kinetic parameters

Kinetic experiments were carried out both in batch and flow reactors type 1 and type 2 with defined procedures. The batch experiments were conducted first with concentrations of 0.02 N of ethyl acetate and sodium hydroxide, volumes of 100 mL each. Experiments were performed at three different temperatures such as 26.5, 33 and 44°C respectively. An estimated quantity of ethyl acetate was charged to the reactor and the desired temperature was set through the circulator. An agitation of around 300 RPM was set using the overhead motor connected to the reactor. Once the temperature is stable, the calculated volume of freshly prepared sodium hydroxide solution was dosed into the reactor at one shot, simultaneously the stopwatch was started. A change in the conductivity was noted over time. As the reaction progresses, the conductivity value will decrease, like sodium hydroxide being used in the reaction to form sodium acetate in the solution. The decrease in the concentration of sodium hydroxide was measured against conductance. The C₀, C_t, and C_∞ are the specific conductance of reaction mixtures at time zero, t, and infinity. Since the reaction follows second order kinetics, a plot of (C₀ − C_t)/(C_t − C_∞) versus time (Figure 12) was drawn to estimate rate constant (k) using the reliable method suggested in the literature [23]. Reaction conversion (X) was estimated using second-order kinetics, X = (1 − C_A/C_A0) at every time interval, and reported. The reaction conversion was of the order 68% (42 min), 67% (40 min) and 78% (203 min) for temperatures 26.5, 33 and 44°C. A plot of ln k versus T (Figure 13) and ln k/T versus 1/T was plotted (Figure 14) to estimate various thermodynamic parameters such as activation energy, activation enthalpy, activation entropy, and Gibbs free energy of activation. The k values (Table 2) for temperatures 26.5, 33 and 44°C were in the order of 0.14, 0.215, and 0.305 Lmol⁻¹ s⁻¹ respectively.

Figure 12.

Graphical determination of reaction rate constant.

Figure 13.

Arrhenius plot of activation energy.

Figure 14.

Graphical evaluation of thermodynamic properties.

Temperature, K	1/T, K-1	Reaction rate constant, L/mol/s	ln k	ln k/T
299.5	0.003339	0.14	−1.96611	−0.00656
306	0.003268	0.215	−1.53712	−0.00502
317	0.003155	0.305	−1.18744	−0.00375
Slope of graph of ln k/T verses 1/T = −14.918
Intercept of ln k/T verses 1/T = 0.0434
Activation enthalpy: ∆H = −124.02 kJ/mol
Activation entropy: ∆S = 197.18 JK^−1 mol^−1
Free energy of activation: ∆G = 65.24 kJ/mol

Table 2.

Thermodynamic parameters of saponification reaction.

A plot of ln k versus 1/T was plotted (Figure 13 and Table 3) to estimate activation energy, the slope of the curve is −4118.5 and intercept of 11.837 to yield activation energy of 34.24 kJ/mol and Arrhenius constant of 8.05 × 10⁶ min⁻¹ using the formula k = Ae−Ea/RT, where k = rate constant at temperature T, Ea = activation energy, R = universal gas constant and A = Arrhenius constant. The other thermodynamic parameters were estimated using the Eyring-Polanyi Equation [23], through plotting ln k/T versus 1/T (Figure 14). The slope of the curve was −14.918 and the intercept was 0.0434, from the slope the activation enthalpy was estimated as −124.02 kJ/mol, activation entropy of 197.18 JK⁻¹ mol⁻¹ and Gibbs free energy of activation was 65.24 kJ/mol (Table 2). The results of the rate constant and activation energy for saponification reaction are in good agreement and comparable with the literature [22, 24, 25, 26, 27, 29]. There could be reasonable errors associated with the sensitivity of conductivity probe and methods of estimation reported by various authors reported in the literature [22].

Temperature, °C	Temperature, K	1/T, K^−1	Reaction rate constant, L/mol/s	ln k
26.5	299.5	0.00334	0.14	−1.966
33	306	0.00327	0.215	−1.537
44	317	0.00315	0.305	−1.187
The slope of the graph of ln k versus 1/T = −4118.5 K
Activation energy: Ea = 34.24 kJ/mol

Table 3.

Effect of temperature on saponification reaction under batch conditions.

Saponification experiments were conducted in the tubular reactor (type 1) of diameter 1.58 and 3.175 mm with a total reactor volume of 33.5 mL and varying flow rates from 6.7 and 13.4 mL/min respectively. Experiments were performed at two different temperatures such as 26.5 and 44°C. The concentrations of 0.02 N of ethyl acetate and sodium hydroxide solutions were used with varying residence time from 2.5, 5, and 10 min respectively. Once the temperature is stable in the thermostat, two pumps A & B were switched on to initiate the flow of sodium hydroxide solution and ethyl acetate solution into the tubular reactor, which was pre-calibrated for known residence time. Samples were collected regularly at the exit of the tube to measure the conductivity. Estimation of reaction conversion(X) was obtained using the standard irreversible bimolecular second-order equation, X = (1 − (C_A/C_A0)), and rate constants were estimated using equation X_A/(1 − X_A) = k C_A0 t individually and averaged across experiments. The conversions are in the order of 68–76.6% for experiments at 26.5 and 44°C respectively (Figure 15). The k values for temperatures 26.5 and 44°C were in the order of 0.347 and 0.419 Lmol⁻¹ s⁻¹ respectively.

Figure 15.

A plot of reaction conversion verses residence time in tubular reactor (type-1).

Further saponification experiments were conducted in a packed bed reactor (type 2) of diameter and length of the reactor as 24 and 240 mm respectively. The total volume of the reactor is around 105 mL with packing and 56 mL as an available volume for the reaction. The experiments were conducted under gravity and against gravity flow to check the performance of the reactor.

The flow rates for gravity flow experiments were in the range of 6.7, 7.8, and 8.4 mL/min respectively. Experiments were performed at two different temperatures such as 26.5 and 44°C. The concentrations of 0.02 N of ethyl acetate and sodium hydroxide solutions were used with varying residence time from 6.66, 7.17, and 8.35 min respectively. Once the temperature is stable in the thermostat, two pumps A & B were switched on to initiate the flow of sodium hydroxide solution and ethyl acetate solution into the reactor, which was pre-calibrated for known residence time. Samples were collected regularly at the exit of the tube to measure the conductivity. Estimation of reaction conversion (X) was obtained using a standard irreversible bimolecular second-order equation, X = (1 − (C_A/C_A0)), and rate constants were estimated using equation X_A/(1 − X_A) = k C_A0 t individually and averaged across experiments. The conversions are in the order of 56–63% for experiments at 26.5 and 44°C respectively (Figure 16). The k values for temperatures 26.5 and 44°C were in the order of 0.167 and 0.171 Lmol⁻¹ s⁻¹ respectively.

Figure 16.

A plot of reaction conversion verses residence time in packed bed reactor (type 2) under gravity flow.

Similar experiments were conducted in a packed bed reactor (type 2) against gravity flow through feeding the streams from the bottom of the reactor to minimize the channeling effect in the packed bed reactor.

The flow rates for gravity flow experiments were in the range of 6.8, 7.8, and 8.4 mL/min respectively. Experiments were performed at two different temperatures such as 26.5 and 44°C. The concentrations of 0.02 N of ethyl acetate and sodium hydroxide solutions were used with varying residence time from 6.66, 7.17, and 8.235 min respectively. Once the temperature is stable in the thermostat, two pumps A & B were switched on to initiate the flow of sodium hydroxide solution and ethyl acetate solution from the bottom of the reactor, which was pre-calibrated for known residence time. Samples were collected regularly at the exit of the tube to measure the conductivity. Estimation of reaction conversion (X) was obtained using a standard irreversible bimolecular second-order equation, X = (1 − (C_A/C_A0)), and rate constants were estimated using equation X_A/(1 − X_A) = k C_A0 t individually and averaged across experiments. The conversions are in the order of 63.7–73.3% for experiments at 26.5 and 44°C respectively (Figure 17). The k values for temperatures 26.5 and 44°C were in the order of 0.22 and 0.288 Lmol⁻¹ sec⁻¹ respectively.

Figure 17.

A plot of reaction conversion verses residence time in packed bed reactor (type-2) under gravity flow.

A new set of experiments was conducted in tubular bed reactor (type 1) submerged in Sonicator bath with sonication frequency (40 Hz) and performed experiments under the following conditions to check the effect of sonication on reaction kinetics under identical conditions.

The flow rates were in the range of 3.35, 6.7, and 13.4 mL/min respectively. Experiments were performed at two different temperatures such as 26.5 and 44°C. The concentrations of 0.02 N of ethyl acetate and sodium hydroxide solutions were used with varying residence time from 2.5, 5, and 10 min respectively. Once the temperature is stable, two pumps A & B were switched on to initiate the flow of sodium hydroxide solution and ethyl acetate solution to the reactor, which was pre-calibrated for known residence time. Samples were collected regularly at the exit of the tube to measure the conductivity. Estimation of reaction conversion(X) was obtained using a standard irreversible bimolecular second-order equation, X = (1 − (C_A/C_A0)), and rate constants were estimated using equation X_A/(1 − X_A) = k C_A0 t individually and averaged across experiments. The conversions are in the order of 59–72.3% for experiments at 26.5 and 44°C respectively (Figure 18). The k values for temperatures 26.5 and 44°C were in the order of 0.30 and 0.374 Lmol⁻¹ s⁻¹ respectively.

Figure 18.

A plot of reaction conversion verses residence time in tubular reactor (type-2) under sonication bath.

5. Conclusions

In the present work, customized flow reactors were designed, fabricated, and characterized through standard methodologies available in the literature. The characterization of the reactors was through RTD studies followed by estimation of various dimensionless parameters to understand the behavior such as E, F and C curves, mean residence time, variance, skewness factor, Reynolds number, Bodenstein number, Dispersion coefficients, and Damköhler number. The results have shown a noteworthy impact on these reactor designs, especially the tubular reactor and packed bed reactor under various operating regimes. The type 1 reactor falls under the transitional region and type 2 reactor falls under the laminar region. It could be concluded that both the reactors have varying degrees of back mixing observed across process conditions. In the case of dispersion, a smaller dispersion was found for type 1 and reasonably large dispersion in type 2 reactor, also the diffusion occurs much faster than the reaction, thus diffusion reaches equilibrium well before the reaction is at equilibrium for type 1 reactor and diffusion-limited system for type 2 reactor. Overall, the behavior of reactor type 1 is more or like the plug flow and reactor type 2 is behaving far from ideal conditions of the plug flow reactor. The spread of distribution was almost twice in a packed bed reactor in comparison with the tubular reactor.

Similarly, the reaction conversion across these reactors have shown significant variation across the reactor types under identical conditions. A significant reduction in residence time was observed in type 1 reactor versus type 2 and batch reactor to achieve similar or equivalent conversion. There is no much impact of ultrasonication on the reaction kinetics of type 1 reactor designs for the given reaction conditions. As a path forward, these reactors could be tested with other reactions or modify the design factors to understand the influence of design and operating conditions.