A Comparison between Continuous and Batch Processes to Capture

Subscriber access provided by UNIVERSITY OF ADELAIDE LIBRARIES

Full Paper

A comparison between continuous and batch processes to capture aldehydes and ketones by using a scavenger resin Andreza D.M. Mendonça, Alline B. V. de Oliveira, and João Cajaiba Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.7b00256 • Publication Date (Web): 11 Oct 2017 Downloaded from http://pubs.acs.org on October 11, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Organic Process Research & Development is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 18

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Organic Process Research & Development

A comparison between continuous and batch processes to capture aldehydes and ketones by using a scavenger resin Andreza D.M. Mendonça, Alline V. B. de Oliveira, João Cajaiba* Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Química, NQTR, Rua Hélio de Almeida 40, Rio de Janeiro, Brasil *[email protected]

1 ACS Paragon Plus Environment


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 18

TOC graphic


Page 3 of 18

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Abstract

A low-cost isoniazid-based scavenger resin was previously prepared and successfully used to capture aldehydes and ketones in solution by using a batch approach. The present work compares batch and continuous processes in relation to the preparation of the scavenger resin ant the effectiveness of cyclohexanone scavenging. The batch preparation of the resin proved to be the better choice because the resin produced in the continuous flow suffered deformation on its surface that prevented access to the active sites in the internal porous polymer matrix. Conversely, the continuous-flow approach presented higher capturing yields than the batch. The optimized scavenging process was successfully used to remove formaldehyde present in a solution and the carbonyl compounds present in an ethanolic extract of Cymbopogon citratus.

Keywords: scavenger resin, Amberlyst, continuous process, batch process, formaldehyde

Cymbopogon citratus.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 18

1. Introduction Polymer reagents are those which possess reactive groups (either covalently or ionically bonded to a macromolecular support) that can be used as reagents, catalysts, and scavengers mainly due to the simplification of the process of separating and isolating products in comparison with the classical reactions in solution1-7. Scavenger resins are polymers with bound functional groups that react with by-products, impurities, or excess reagents produced in a reaction or compounds of interest present in extracts. The easiness of removal by filtration is one of the main advantages of these materials8-13. Carbonyl compounds, such as aldehydes and ketones, are present in essential oils from plant extracts14-20. When these materials appear in tiny amounts, their isolation/characterization may present great experimental difficulties21. Sulfonyl hydrazine–supported reagents are used for capturing aldehydes and ketones forming sulfonyl hydrazones22-27. The syntheses for producing this type of supported reagents are time-consuming and require high-cost or dangerous reagents. An economically more attractive option is to obtain a similar reagent by reacting an ion exchange resin, by means of an acid-base reaction, with a basic nitrogen of isoniazid (a drug used to treat tuberculosis28-29), as shown in Scheme 124.

Scheme 1. Reaction of isoniazid with ion exchange resin to produce the new resin, Amb15-Iso.

By using the scavenger resin produced according to Scheme 1, the authors have captured aldehydes and ketones present in solutions by using a batch approach24. It is well-known that the search for new technologies is growing due to the possible increase in productivity30-31. The use of continuous-flow reactions is one of the main strategies used to increase productivity due to its advantages in the purification/separation steps. Tubular reactors can be used in flow reactions. They consist of a container with the solid support through which reagents are pumped under a specific flow rate that determines the residence


Page 5 of 18

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


time according to the volume of the reactor. In this case, the solution may recycle until saturation of the solid support used32-36. The present work aims to perform a comparison between the preparation of the scavenger resin by batch and continuous processes and evaluate the performance of scavenging by both continuous and batch processes.

2. Experimental methods 2.1. Apparatus All the reactions were performed using a Mettler Toledo EasyMax 102 Advanced Synthesis Workstation automatic reactor under stirring and controlled temperature. Immobilizations were carried out with real-time monitoring in a continuous-flow cell coupled to a Mettler Toledo ReactIR iC10 spectrophotometer. Reactions were performed in a continuous system using a high-performance liquid chromatography support (HPLC) column (7.8 × 300 mm) packed with resin as a cartridge reactor, into which the solution was injected with a Waters 515 HPLC pump. Figure 1 shows a schematic diagram of the reactions in the continuous system. Initially, the solution containing the substrate of interest passes through a detector, which in this case is the flow cell coupled to the spectrophotometer. Subsequently, the solution goes through the pump and is injected into the cartridge under a chosen flow rate before returning to the reaction vessel. The flow continues until the polymeric cartridge is saturated.

HPLC pump

Detector

Substrate in solution

Cartridge reactor

Figure 1. Schematic diagram of the reactions in the continuous system.

2.2. Procedures



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 18

2.2.1. Synthesis of Amb15-Iso polymeric reagent under real-time monitoring by attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR)

Batch system (Amb15-Iso (B)): The batch system was set up using a 100.0 mL glass vessel, a flow cell unit attached to the ATR-FTIRht source, and a pulse pump responsible for keeping the solution flowing through the detector. Initially, 80.0 mL of the solvent (H2O) was added to the glass vessel under magnetic stirring at 150 rpm and 25ºC. Next, 5.0 g of isoniazid was added. After its complete solubilization, 7.5 g of the resin (Amberlyst-15) was added to the solution. Upon reaction completion, the resin was drained by vacuum filtration and washed with water and methanol. Afterward, the resin was oven-dried at 60°C for 12 h.

Continuous-flow system (Amb15-Iso (F)): The continuous-flow system was set up using a 100.0 mL glass vessel, a flow cell unit coupled to the ATR-FTIR, and an HPLC pump responsible for maintaining the continuous flow of the solution. The cartridge reactor was packed with 7.5 g of resin (Amberlyst-15), sealed at both ends, and weighed. Subsequently, 80.0 mL of the solvent (H2O) and 5.0 g of isoniazid were added to the glass vessel and kept under magnetic stirring at 150 rpm and 25°C. The pump was started at the chosen flow rate (1, 2, 3, or 4 mL/min). When the reaction ended, the cartridge reactor was cleaned with water and methanol. The resin was oven-dried at 80°C for 24 h.

2.2.2. Capture of cyclohexanone by Amb15-Iso (B) and Amb15-Iso (F)

Batch system: The batch system was set up using a 100.0 mL glass vessel, a flow cell unit attached to the ATR-FTIR, and a pulse pump responsible for keeping the solution flowing through the detector. Initially, 50.0 mL of the solvent (ethanol) was added to the glass vessel under magnetic stirring at 150 rpm and 25ºC. Next, 256.0 µL of cyclohexanone was added. After its complete solubilization, 7.5 g of the resin Amb15-Iso (B) was added to the solution. Upon reaction completion, the resin was drained by vacuum filtration and washed with water and methanol. Afterward, the resin was oven-dried at 60°C for 12 h.

Continuous-flow system: The continuous-flow system was set up using a 100.0 mL glass vessel, a flow cell unit coupled to the ATR-FTIR, an HPLC pump responsible for maintaining the continuous flow of the solution, and the cartridge reactor containing the resin Amb15-Iso (F). Subsequently, 50.0 mL of the solvent (ethanol) and 256.0 µL of cyclohexanone were added to the glass vessel and kept under 6 ACS Paragon Plus Environment

Page 7 of 18

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


magnetic stirring at 150 rpm and 25°C. The pump was started at the chosen flow rate (1, 2, 3, or 4 mL/min). When the reaction ended, the cartridge reactor was cleaned with water and methanol. The resin was oven-dried at 80°C for 24 h.

2.2.3. Scavenging of Citral A and B from an ethanolic solution of Cymbopogon citratus by Amb15-Iso (B).

Continuous-flow system: The continuous-flow system was set up using a 100.0 mL glass vessel, a flow cell unit coupled to the ATR-FTIR, and an HPLC pump responsible for maintaining the continuous flow of the solution. The cartridge reactor was packed with 7.5 g of resin Amb15-Iso (B), sealed on both ends, and weighed. Subsequently, 60.0 mL of the ethanolic solution of Cymbopogon citratus* was added to the glass vessel and kept under magnetic stirring at 150 rpm and 25°C. The pump was started at the flow rate 3 mL/min. When the reaction ended, the cartridge reactor was cleaned with water and methanol. The resin was oven-dried at 80°C for 24 h. * The ethanolic extract was produced from 8 g of lemongrass under reflux for 1 h using a Soxhlet apparatus.

3. Results and Discussion 3.1. Comparison between batch and continuous flow processes to produce scavenger resin Amb15-Iso The scavenger resin was prepared by reacting isoniazid with Amberlyst-15 to the resin named Amb15-Iso (B). The batch process as previously described11; consisted of the simple mixing of isoniazid and Amberlyst-15 in water (Scheme 1). The experimental setup to produce the scavenger resin by using a continuous process (Amb15-Iso (F)) is presented in Figure 1. The monitoring of the reaction of Amberlyst-15 with isoniazid was performed in real time by using ATR-FTIR for both the continuous and the batch approaches. The time-dependent 3D ATR-FTIR graph presented in Figure 2 shows the incorporation reaction of isoniazid in water



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 8 of 18

(pure solvent spectrum subtracted) for the continuous process and one selected spectrum of isoniazid in water with descriptions of its major bands.

Addition of isoniazid

Start of immobilization

Figure 2. Three-dimensional ATR-FTIR graph of the incorporation reaction of isoniazid in water (pure solvent spectrum subtracted) and one selected spectrum of isoniazid in water with descriptions of its major bands.

The spectra shown in Figure 2 correspond only to the isoniazid absorptions, as water peaks were subtracted from the raw spectra. The ATR-FTIR flow cell can detect only substances present in solution; therefore, as the isoniazid reacts with Amberlyst-15, its concentration decreases, and so does its infrared absorptions. It is important to note that excess isoniazid was used to ensure complete incorporation of this substrate into the Amberlyst-15 resin. Figure 3 shows the intensities of isoniazid 1555 cm-1 ring CN symmetric stretching for isoniazid incorporation in the batch and continuous approaches.


Page 9 of 18

Addition of Amberlyst-15

Isoniazid 1555 cm-1 absorption (%)

90 75 60

Reaction equilibrium 45 30 15

a) Batch process

Isoniazid addition in water

0 0

10

20

30

40

50

60

70

80

90

100

Time (minutes)

Isoniazid 1555 cm-1 absorption (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Beginning of isoniazid incorporation reaction inside the cartridge reactor containing Amberlyst-15

90 75

Reaction equilibrium

60 45 30

Isoniazid addition in water

15

b) Continuous process

0 0

20

40

60

80

100

120

140

160

Time (minutes) Figure 3. Normalized trend for the incorporation of isoniazid by the Amberlyst-15 resin measured by ATRFTIR: a) batch process; b) continuous process 3 mL/min flow rate.

It is important to emphasize that excess isoniazid was used to ensure complete incorporation of this substrate in Amberlyst-15 resin for both continuous and batch processes and that no leaching of isoniazid was observed. Therefore, the trend corresponding to the isoniazid absorptions only had their intensities decreased to approximately 40% of the initial concentration, presenting similar incorporation capacity for both processes. The slight differences between the incorporation capacities can be evaluated comparing the mean values presented in Table 1 that were calculated by using equation (1).



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 18

Capacity = (Cfinal – Cinitial). Vsolution / mresin

(1)

Table 1. Capacity of incorporation of isoniazid by Amberlyst-15. Regimen

Flow-rate

Mean capacity

Standard

t (x)*

(mL/min)

(mmol/g)

deviation

Batch

-

2.38

0.10

4.58

Continuous

1

2.55

0.11

2.70

Continuous

2

2.71

0.08

0.86

Continuous

3

2.77

0.09

-

Continuous

4

2.45

0.10

4.41

*(x) t-test determined in relation to 3 mL/min flow rate; α=0.05, where t-critic = 2.9.

In the t-test a hypothesis is created between two mean values with their variances in which, for the hypothesis to be true, the calculated value t must be smaller than the critical value (tabled value for each degree of freedom). Otherwise, the hypothesis is false and the systems are considered different. By considering that the flow rate of 3 mL/min has reached the higher value of capacity, this flow rate was chosen as a standard of comparison with the other flow rate values. Production of Amb15-Iso in continuous flow presented higher capacities than the material prepared by using the batch approach. The data shown in Table 1 correspond to the mean values (each result performed as triplicates). The capacity of incorporation was defined by the number of moles of isoniazid consumed per gram of resin, calculated gravimetrically through equation (1) and by using a calibration curve by ATR-FTIR that is available as Supporting Information. Based on these data, the confidence intervals were calculated using the comparison test of the means with a 95% confidence interval to compare the systems and to determine if there exists an influence of the flow rate in the capacity of incorporation (Table 1). It was found that the incorporation capacity of isoniazid in 3 mL/min is not statistically the same as the batch and the continuous process by using a 4mL/min flow rate, assuming a 95% confidence interval. In relation to the flow rates of 1 and 2 mL/min, it can be said that there are no significant differences between them, and any of these flows can be used. It is known that changes in the flow affect the kinetics of the reaction, because the longer the residence time, the longer the time until the equilibrium of the reaction is reached. Therefore, within this confidence interval, the flow rate of 3 mL/min, is considered the most efficient 10 ACS Paragon Plus Environment

Page 11 of 18

system for the immobilization of isoniazid by Amberlyst-15 resin, because it has the shortest residence time. 3.2. Comparison between continuous and flow processes for capturing carbonyl compounds using Amb15-Iso Cyclohexanone was used as a standard carbonyl compound to evaluate the scavenging performance of Amb15-Iso (F) produced by continuous process and Amb15-Iso (B) for the batch approach. Figure 4 shows cyclohexanone C=O stretching absorption (1701 cm-1) during the process of scavenging. 100

Capture started by the addition the scavenger resin 80

Cyclohexanone 1701 cm -1 (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


60

Establishing the reaction equilibrium

40

20

Addition of cyclohexanone (ethanol solvent) 0 0

10

20

30

40

50

60

70

80

90

Time (min) Figure 4. Cyclohexanone carbonyl stretching absorption (1701 cm-1) before and after Amb15-Iso addition.

Table 2 shows the mean scavenging capacity, under different flow rates, for Amb15-Iso produced by both continuous (F) and batch (B) processes. Table 2. Capturing capacities of Amb15-Iso as a function of the flow rate. Mean capturing capacity* Flow-rate

Amb15-Iso (F)

Amb15-Iso (B)

(mL/min) 1.0

0.1251

0.1758



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

2.0

0.1283

0.1977

3.0

0.1332

0.2193

4.0

0.1027

0.1678

Page 12 of 18

*Where (F) is the resin produced in flow conditions (3 mL/min) and (B) corresponds to the material prepared in batch conditions.

By considering the results shown in Table 1, it would be expected that Amb15-Iso produced in the continuous flow by using 3 mL/min flow rate would present the highest scavenging capacity. Conversely of what was expected, the capturing capacities of Amb15-Iso produced in continuous mode (F) presented lower capturing capacities than the resin produced by the batch process (B). These results suggest that the resin prepared in the continuous process produced a material with fewer available active sites than the resin produced in batch conditions. Aiming at evaluating this hypothesis, optical micrographies of Amberlyst-15, Amb15-Iso (F), and Amb15-Iso (B) were acquired and are shown in Figure 5.

Figure 5. Optical micrographies (amplification of 55x) of (a) Amberlyst-15, (b) Amb15-Iso (B), and (c) Amb15-Iso (F). The white cycles that appeared in the images are due to the light backscattering.


Page 13 of 18

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


All materials, as expected, presented spherical shape. Different from Amb15-Iso (B) and Amberlyst-15, Amb15-Iso (F) presented dark regions in its surface. To check what these black points mean, scanning electron microscope (SEM) micrographies of Amb15-Iso were obtained (Figure 6).

Figure 6. SEM micrography of Amb15-Iso (F), amplification of 245x and 540x, respectively.

By zooming in on the dark areas, it is possible to observe that they correspond to surface damage. The kneaded points may hinder access to the active sites present in the inner porous polymer matrix of the resin, leading to a diminution of the capacity of the active groups to react with the carbonyl compound. This phenomenon was probably triggered by packing the resin into the cartridge reactor during the immobilization reaction, since isoniazid, when incorporated into the resin, tends to increase its circumference and thus lead to kneading of the surfaces. This was observed in all resins synthesized in a continuous flow system. These depressions have resulted in loss of resin reactivity in the sequestration stage of aldehydes and ketones, since some active sites may have become inaccessible. With the knowledge that the Amb15-Iso (B) creates products with better capturing performance than the materials produced in continuous flow, this material was used to evaluate cyclohexanone capturing by both batch and continuous processes (Table 3).



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 18

Table 3. Continuous flow modes by using Amb15-Iso (B). Flow rate

Mean capturing

Standard

t (x)* – mean

(mL/min)

capacity (mmol/g)

deviation

comparison test

Batch

-

0.1567

0.0203

3.42

Continuous

1

0.1758

0.0126

11.3

Continuous

2

0.1977

0.0295

1.27

Continuous

3

0.2193

0.0243

-

Continuous

4

0.1678

0.0127

7.01

Regimen

*(x) t-test determined in relation to 3 mL/min flow rate; α=0.05, where t-critic = 2.9.

From the t-test results, the capture capacity of cyclohexanone at 3 mL/min is statistically different from the batch as well as the flow rates of 1 and 4 mL/min, with a certainty of 95%, and can be considered equivalent to the 2 mL/min flow rate. Considering that the flow rate of 3 mL/min has a shorter residence time, it is possible to state that the flow rate of 3 mL/min is the most adequate to perform carbonyl-capturing reactions. Thus, the most efficient route is producing Amb15-Iso by mixing Amberlyst-15 with isoniazid in water (batch process), packing the cartridge reactor with this material, and performing the capturing reaction by using a 3 mL/min flow rate. After determining the most appropriate procedure of producing and using the scavenger resin, Amb15-Iso (B) was used for scavenging only the carbonyl compounds present in a Cymbopogon citratus ethanolic extract. Figure 7a presents the gas chromatography (GC) analysis of the extract that presented three major compounds: myrcene, citral A (geranial) and citral B (neral). The corresponding mass spectra are presented in the Supporting Information section. This extract was pumped into a cartridge reactor containing Amb15-Iso (B) by using a 3 mL/min flow rate (Figure 7b). As can be seen, the scavenger resin can remove the total amount of carbonyl compounds present in the extract.


Page 15 of 18

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


neral

myrcene

geranial

Figure 7a. GC analysis of the Cymbopogon citratus ethanolic extract.

myrcene

Figure 7b. GC analysis of the Cymbopogon citratus ethanolic extract after sequestration of aldehydes.

The scavenging of formaldehyde, that is a trace contaminant in some pharmaceutical excipients37, was successfully achieved by using Amb15-Iso (B) in a continuous process. It is known that formaldehyde is not readily amenable to gas chromatographic (GC) with flame ionization detection (FID) and cannot be easily analyzed by mass spectrometry (MS). The reaction of formaldehyde with 2,4dinitrophenylhydrazine produces a 2,4-dinitrophenylhydrazone readily analyzed by GC38. These results are presented in the Supporting Information Section.

4. Conclusion The simple mixing of Amberlyst-15 with isoniazid in water (batch approach) followed by filtration, drying, and packing the resin in a cartridge proved to be the most indicated approach for producing the scavenger resin, because the continuous process of pumping an



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 18

isoniazid solution into a cartridge containing Amberlyst-15 caused the kneading of the spherical surface of the scavenger resin leading to a diminution of the scavenging capacity by hindering the access to the inner porous polymer matrix of the resin. The scavenging performance of Amb15-Iso (B) to capture carbonyl compounds in solution was successful by using both the continuous and batch processes. The continuous process presented slightly higher capacity than the batch process. This small difference in the scavenging performance could not be detected by real-time monitoring using ATR-FTIR. The statistic t-test of mean comparison was successfully used to quantitatively compare the differences between the continuous and batch processes.

Supporting Information The mass spectra of myrcene, neral and geranial are presented (Figures S1-S3). The calibration curves of the CG analysis of isoniazid and cycloexanone (Figures S4 and S5). The GC analysis of formaldehyde 2,4-dinitreophenylhydrazone (Figure S6) and the GC showing formaldehyde scavenging (Figure S7).

Acknowledgment We gratefully acknowledge the financial support of FINEP; Andreza D. M. Mendonça acknowledges CAPES and FAPERJ for a M.Sc. grant.

5. References 1.

Raillard, S. P.; Ji, G.; Mann, A. D.; Baer, T. A. Organic Process Research &

Development 1999, 3, 177-183. 2.

Eifler-Lima, V. L.; Graebin, C. S.; Uchoa, F. D.; Duarte, P. D.; Correa, A. G. Journal

of the Brazilian Chemical Society 2010, 21, 1401-1423. 3.

Drewry, D. H.; Coe, D. M.; Poon, S. Medicinal Research Reviews 1999, 19, 97-148.

4.

Bhattacharyya, S. Combinatorial Chemistry & High Throughput Screening 2000, 3,

65-92. 5.

Marquardt, M.; Eifler-Lima, V. L. Quimica Nova 2001, 24, 846-855.

6.

Merrifield, R. B. Journal of the American Chemical Society 1963, 85, 2149-2154.

7.

Barbaras, D.; Brozio, J.; Johannsen, I.; Allmendinger, T. Organic Process Research &

Development 2009, 13, 1068-1079. 8.

Miyamoto, H.; Sakumoto, C.; Takekoshi, E.; Maeda, Y.; Hiramoto, N.; Itoh, T.; Kato,

Y. Organic Process Research & Development 2015, 19, 1054-1061. 16 ACS Paragon Plus Environment

Page 17 of 18

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


9.

Guinó, M.; Brulé, E.; de Miguel, Y. R. Journal of Combinatorial Chemistry 2003, 5,

161-165. 10.

Ley, S. V.; Baxendale, I. R. Nat Rev Drug Discov 2002, 1, 573-586.

11.

Bhattacharyya, S. Current Opinion in Drug Discovery & Development 2004, 7, 752-

764. 12.

Garcia, J. G. Combinatorial Chemistry, Pt B 2003, 369, 391-412.

13.

Solinas, A.; Taddei, M. Synthesis-Stuttgart 2007, 2409-2453.

14.

Patel, S. Food Additives & Contaminants: Part A 2015, 32, 1049-1064.

15.

Chen, Z. C.; Mei, X.; Jin, Y. X.; Kim, E. H.; Yang, Z. Y.; Tu, Y. Y. Journal of the

Science of Food and Agriculture 2014, 94, 316-321. 16.

Tak, J. H.; Jovel, E.; Isman, M. B. Journal of Pest Science 2017, 90, 735-744.

17.

Santos, E. S.; Balseiro-Romero, M.; Abreu, M.; Macias, F. Journal of Geochemical

Exploration 2017, 174, 84-90. 18.

Bouzenna, H.; Hfaiedh, N.; Giroux-Metges, M. A.; Elfeki, A.; Talarmin, H.

Biomedicine & Pharmacotherapy 2017, 87, 653-660. 19.

Bajer, T.; Janda, V.; Bajerova, P.; Kremr, D.; Eisner, A.; Ventura, K. Journal of Food

Science and Technology-Mysore 2016, 53, 1576-1584. 20.

Yu, Y. J.; Ni, S.; Wu, F.; Sang, W. G. Journal of Essential Oil Bearing Plants 2016,

19, 1170-1180. 21.

Bakaï, M.-F.; Barbe, J.-C.; Moine, V.; Birot, M.; Deleuze, H. Tetrahedron 2014, 70,

9421-9426. 22.

Zhu, Q.; Sun, Z.; Jiang, Y.; Chen, F.; Wang, M. Molecular Nutrition & Food

Research 2011, 55, 1375-1390. 23.

Blasi, M.; Barbe, J.-C.; Maillard, B.; Dubourdieu, D.; Deleuze, H. Journal of

Agricultural and Food Chemistry 2007, 55, 10382-10387. 24.

de Oliveira, A. V. B.; Kartnaller, V.; Pedrosa, M. S.; Cajaiba, J. Journal of Applied

Polymer Science 2015, 132. 25.

Gabrielson, G.; Samuelson, O. Acta Chemica Scandinavica 1952, 6, 729-737.

26.

Emerson, D. W.; Emerson, R. R.; Joshi, S. C.; Sorensen, E. M.; Turek, J. E. The

Journal of Organic Chemistry 1979, 44, 4634-4640. 27.

Zhu, M. Z.; Ruijter, E.; Wessjohann, L. A. Organic Letters 2004, 6, 3921-3924.

28.

Stagg, H. R.; Lipman, M. C.; McHugh, T. D.; Jenkins, H. E. International Journal of

Tuberculosis and Lung Disease 2017, 21, 129-139.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

29.

Page 18 of 18

Ruchita; Nanda, S.; Pathak, D.; Mathur, A. International Journal of Pharmaceutical

Sciences and Research 2017, 8, 2341-2359. 30.

Hessel, V. Chemical Engineering & Technology 2009, 32, 1655-1681.

31.

O'Brien, M. K.; Kolb, M.; Connolly, T. J.; McWilliams, J. C.; Sutherland, K. Drug

Discovery Today 2011, 16, 81-88. 32.

Baxendale, I. R. Journal of Chemical Technology & Biotechnology 2013, 88, 519-

552. 33.

Baxendale, I. R.; Brocken, L.; Mallia, C. J. Green Processing and Synthesis 2013, 2,

211-230. 34.

Fitzpatrick, D. E.; Battilocchio, C.; Ley, S. V. Organic Process Research &

Development 2016, 20, 386-394. 35.

Wiles, C.; Watts, P. Green Chemistry 2012, 14, 38-54.

36.

Illg, T.; Löb, P.; Hessel, V. Bioorganic & Medicinal Chemistry 2010, 18, 3707-3719.

37.

Grodowska, K.; Parczewski, A. Acta Poloniae Pharmaceutica 2010, 67, 3-12.

38.

Soman, A.; Qiu, Y.; Chan Li, Q. Journal of Chromatographic Science 2008, 46, 461-

465.


A Comparison between Continuous and Batch Processes to Capture

Recommend Documents