Continuous flow hydrogenation of methyl and ethyl levulinate: an alternative route to γ-valerolactone production

Heterogeneous continuous transformation of methyl levulinate (ML) and ethyl levulinate (EL) to γ-valerolactone (GVL), as a promising C5-platform molecule was studied at 100°C. It was proved that the H-Cube® continuous hydrogenation system equipped with 5% Ru/C CatCart® is suitable for the reduction of both levulinate esters. While excellent conversion rates (greater than 99.9%) of ML and EL could be achieved in water and corresponding alcohols, the selectivities of GVL were primarily affected by the solvent used. In water, 100% conversion and ca 50% selectivity that represent ca 0.45 molGVL gmetal−1 h−1 productivity towards GVL, were obtained under 100 bar of total system pressure. The application of alcohols as a solvent, which maintained high conversion rates up to 1 ml min–1 flow rate, resulted in lower productivities (less than 0.2 molGVL gmetal−1 h−1) of GVL. Therefore, from a synthesis point of view, the corresponding 4-hydroxyvalerate esters could be obtained even at a higher reaction rate. The addition of sulfonated triphenylphosphine ligand (TPPTS) allowed reduction of the system pressure and resulted in the higher selectivity towards GVL.

(GVL). Key to this process is the H-Cube hydrogenation system. One benefit of the optimised method is that the H2 mediated reduction of both levulinate esters proceeds in water and alcoholic solvents (methanol and ethanol). The authors have diligently addressed the reviewer comments from previous iterations of the manuscript, and these efforts have presumably improved the previously submitted versions of the manuscript. However, a number of inadequacies remain: 1. The scalability of the process is not discussed. The practical synthesis of GVL mandates multitonne reduction of methyl-and ethyl-levulinate. Did the authors perform gram scale (tens of grams) synthesis to validate the optimized process? 2. The SI is not instructive, and the Tables contain acronyms that are not adequately described. It is therefore difficult to deconvolute the data and the SI is of very limited value in current format. 3. In the SI, Table S1 appears to be directly copied from the marketing brochure and offers no scientific value within the context of the manuscript.
The study does make a minor contribution to the field of continuous flow hydrogenation in describing a method to screen the reduction methyl-and ethyl-levulinate esters to gammavalerolactone (GVL). However, the H-Cube is a well-established laboratory scale technology and the use of this apparatus for high throughput screening of heterogenous catalysis (CatCarts) was rapidly established following the inception of the H-Cube device. Of greater concern is the lack of innovative chemistry in the manuscript. For example, the authors had an opportunity to develop a multi-step process to furnish GVL derivatives in a single unit operation or to develop a scalable process for GVL. Given that very narrow focus of the manuscript, I conclude that the manuscript is beyond the scope of the journal. I recommend that the manuscript be considered for publication in a specialised engineering journal to ensure better alignment with the journal scope and readership.

Do you have any ethical concerns with this paper? No
Have you any concerns about statistical analyses in this paper? No

Recommendation?
Accept with minor revision (please list in comments)

Comments to the Author(s) Review comments on RSOS-182233
This resubmitted manuscript has answered most of the issues proposed by previous reviewers, and some revisions were given in the revised manuscript. Although the scientific novelty of this work is indeed not so obvious, the researches of the conversion of levulinic esters to GVL on a continuous reactor were attempted and the results are helpful to promote the real application of the synthesis of GVL through this reactor. So this work is more meaningful in viewpoint of engineering. Therefore, I recommend this work published in Royal Society Open Science after Minor Revision. 1. The author claimed that the addition of acids could promote the formation of GVL in two places in the manuscript but no experiment data were provided. The evidences should be given. Thank you for submitting the above manuscript to Royal Society Open Science. On behalf of the Editors and the Royal Society of Chemistry, I am pleased to inform you that your manuscript will be accepted for publication in Royal Society Open Science subject to minor revision in accordance with the referee suggestions. Please find the reviewers' comments at the end of this email. I apologise that this took longer than usual.
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Please add the reaction temperature to the paper abstract.
It would have been informative for the authors to have conducted this reaction with the H-CubePro, say at 150ºC, which may have been accessible to them as one of the authors (Jones) is cited as at ThalesNano.
It is not clear how the level of leach metals were determined -is this by ICP MS? This should be mentioned din the body text.
Please provide an experimental procedure section.
What is the time (flow rate / volume of reagents) to catalyst exhaustion?

Reviewer: 2
Comments to the Author(s) The authors describe a continuous flow method to screen and optimize heterogeneous catalytic conditions for the conversion of methyl-and ethyl-levulinate esters to gamma-valerolactone (GVL). Key to this process is the H-Cube hydrogenation system. One benefit of the optimised method is that the H2 mediated reduction of both levulinate esters proceeds in water and alcoholic solvents (methanol and ethanol). The authors have diligently addressed the reviewer comments from previous iterations of the manuscript, and these efforts have presumably improved the previously submitted versions of the manuscript. However, a number of inadequacies remain: 1. The scalability of the process is not discussed. The practical synthesis of GVL mandates multitonne reduction of methyl-and ethyl-levulinate. Did the authors perform gram scale (tens of grams) synthesis to validate the optimized process? 2. The SI is not instructive, and the Tables contain acronyms that are not adequately described. It is therefore difficult to deconvolute the data and the SI is of very limited value in current format. 3. In the SI, Table S1 appears to be directly copied from the marketing brochure and offers no scientific value within the context of the manuscript.
The study does make a minor contribution to the field of continuous flow hydrogenation in describing a method to screen the reduction methyl-and ethyl-levulinate esters to gammavalerolactone (GVL). However, the H-Cube is a well-established laboratory scale technology and the use of this apparatus for high throughput screening of heterogenous catalysis (CatCarts) was rapidly established following the inception of the H-Cube device. Of greater concern is the lack of innovative chemistry in the manuscript. For example, the authors had an opportunity to develop a multi-step process to furnish GVL derivatives in a single unit operation or to develop a scalable process for GVL. Given that very narrow focus of the manuscript, I conclude that the manuscript is beyond the scope of the journal. I recommend that the manuscript be considered for publication in a specialised engineering journal to ensure better alignment with the journal scope and readership.

Reviewer: 3
Comments to the Author(s) Review comments on RSOS-182233 This resubmitted manuscript has answered most of the issues proposed by previous reviewers, and some revisions were given in the revised manuscript. Although the scientific novelty of this work is indeed not so obvious, the researches of the conversion of levulinic esters to GVL on a continuous reactor were attempted and the results are helpful to promote the real application of the synthesis of GVL through this reactor. So this work is more meaningful in viewpoint of engineering. Therefore, I recommend this work published in Royal Society Open Science after Minor Revision. 1. The author claimed that the addition of acids could promote the formation of GVL in two places in the manuscript but no experiment data were provided. The evidences should be given.