catalysts Article Continuous 2-Methyl-3-butyn-2-ol Selective Hydrogenation on Pd/γ-Al2O3 as a Green Pathway of Vitamin A Precursor Synthesis Antonio J. Fernández-Ropero 1 , Bartosz Zawadzki 1 , Emil Kowalewski 1, Izabela S. Pieta 1 , Mirosław Krawczyk 1 , Krzysztof Matus 2 , Dmytro Lisovytskiy 1 and Anna Sr˛ebowata´ 1,* 1 Institute of Physical Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland; [email protected] (A.J.F.-R.); [email protected] (B.Z.); [email protected] (E.K.); [email protected] (I.S.P.); [email protected] (M.K.); [email protected] (D.L.) 2 Materials Research Laboratory, Silesian University of Technology, Konarskiego 18A, 44-100 Gliwice, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-22-343-3320 Abstract: In this work, the effect of pretreatment conditions (10% H2/Ar flow rate 25 mL/min and ◦ ◦ 400 C, 3 h or 600 C, 17 h) on the catalytic performance of 1 wt.% Pd/γ-Al2O3 has been evaluated for hydrogenation of 2-methyl-3-butyn-2-ol in continuous-flow mode. Two palladium catalysts have been tested under different conditions of pressure and temperature and characterized using ◦ various physicochemical techniques. The catalytic performance of red(400 C)-Pd/γ-Al2O3 and ◦ red(600 C)-Pd/γ-Al2O3 are affected by the coexistence of several related factors like the competition between PdH and PdCx formation during the reaction, structure sensitivity, hydrogen spillover Citation: Fernández-Ropero, A.J.; to the alumina support and presence or absence of Pd–Al species. High-temperature reduction Zawadzki, B.; Kowalewski, E.; Pieta, leads to formation of Pd–Al species in addition to pure Pd. The Pd–Al species which reveal unique I.S.; Krawczyk, M.; Matus, K.; δ− Lisovytskiy, D.; Sr˛ebowata,A.´ electronic properties by decreasing the Pd surface concentration via electron transfer from Pd Continuous 2-Methyl-3-butyn-2-ol to Al, leading to a weaker Pd–Alkyl bonding, additionally assisted by the hydrogen spillover, are Selective Hydrogenation on the sites of improved semi-hydrogenation of 2-methyl-3-butyn-2-ol towards 2-methyl-3-buten-2-ol Pd/γ-Al2O3 as a Green Pathway of (97%)—an important intermediate for vitamin A synthesis. Vitamin A Precursor Synthesis. Catalysts 2021, 11, 501. https:// Keywords: heterogeneous catalysis; flow chemistry; selective hydrogenation; green chemistry doi.org/10.3390/catal11040501 Academic Editors: Kei Manabe and Nicola Della Ca 1. Introduction Many chemical conversions in the pharmaceutical industry involve stoichiometric Received: 29 January 2021 amounts of reagents and, thus, generate large amounts of waste [1]. However, imple- Accepted: 12 April 2021 mentation of catalytic methods (especially in the continuous-flow mode) in this highly Published: 15 April 2021 competitive industry increases the process efficiency, improves energy efficiency and re- cyclability, reduces costs and improves sustainability. The continuous method allows Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in fine-tuning of the contact time between intermediates and the active catalytic phase, which published maps and institutional affil- may result in high selectivity without using additives or a purification step, and turns into iations. a decrease of the E-factor (kg of generated waste/kg of product) [2,3]. In consequence, the pharmaceutical industry’s application of continuous-flow practices is considered one of the most strategic fields of innovation towards greener manufacturing methods, and complies with twelve principles of green chemistry [2,4]. One of the desired products in the pharmaceutical industry is 2-methyl-3-buten-2-ol Copyright: © 2021 by the authors. (MBE) which is obtained by means of partial reduction of 2-methyl-3-butyn-2-ol (MBY) Licensee MDPI, Basel, Switzerland. This article is an open access article (Scheme1). distributed under the terms and MBE is an important intermediate for the industrial synthesis of vitamins A (Scheme S1)[6] conditions of the Creative Commons and E and are present in a large variety of perfumes as aroma compounds [7]. Attribution (CC BY) license (https:// The current manufacturing processes in batch set-ups of this alcohol avoids the com- creativecommons.org/licenses/by/ plete hydrogenation by using, for instance, Lindlar-type catalyst containing Pd (5 wt.%) 4.0/). Catalysts 2021, 11, 501. https://doi.org/10.3390/catal11040501 https://www.mdpi.com/journal/catalysts Catalysts 2021, 11, 501 2 of 19 and Pb (2–3 wt.%) deposited on CaCO3 [8]. However, lead toxicity entails an environmen- tal concern that should not be ignored [9] and the addition of additives to enhance the selectivity results in additional costs due to the necessary separation processes [7]. While it is true that other Pb-free Pd-based catalysts are being used in the synthesis of MBE with Catalysts 2021, 11, x FOR PEER REVIEW 2 of 20 yields of 95–97%, they suffer from high catalyst deactivation due to degradation of the support or sintering of the metal particles [10]. Scheme 1. PathwayScheme 1.ofPathway catalytic of2-methyl-3 catalytic-butyn-2-ol 2-methyl-3-butyn-2-ol hydrogenation hydrogenation [5]. [5]. MBE is an importantHydrogenation intermediate of MBY for hasthe beenindustrial investigated synthesis in of continuous vitamins A flow, (Scheme with a good yield, S1) [6] and E bothand are in gaspresent and in liquid a large conditions variety of [5 ,perfumes11–16]. Most as aroma of these compounds studies have [7]. been carried out The currentusing manufacturing Pd-based catalysts, processes where in batch the metal set-ups particles of this werealcohol supported avoids the on com- a large variety of materials. Yields of 89% and 92% were reached in capillary microreactors using bimetallic plete hydrogenation by using, for instance, Lindlar-type catalyst containing Pd (5 wt.%) Pd25Zn75 [11] and pure Pd nanoparticles [12] both supported on TiO2 and using methanol and Pb (2–3 wt.%) deposited on CaCO3 [8]. However, lead toxicity entails an environmen- as the solvent. Non-negligible values were obtained by Kundra et al., in a 3D printed tal concern that should not be ignored [9] and the addition of additives to enhance the catalytic static mixer. In a solution of 30% isopropanol and 70% water, with colloidal selectivity results in additional costs due to the necessary separation processes [7]. While palladium on titanium silicate as a catalyst [13], 96% conversion and 91% alkene selectivity it is true that other Pb-free Pd-based catalysts are being used in the synthesis of MBE with were achieved at a moderate pressure of 4 bars and a relatively high temperature of 100 yields of 95–97%, they suffer from high catalyst deactivation due to degradation of the ◦C. On the other hand, in the same study, the performance was much lower when using support or sintering of the metal particles [10]. Lindlar catalyst. MBE selectivity over 90% was shown in Al O -coated metallic monolithic Hydrogenation of MBY has been investigated in continuous flow, with2 3 a good yield, reactors featuring hybrid hexadecyl(2-hydroxyethyl)dimethyl ammonium dihydrogen- both in gas and liquid conditions [5,11–16]. Most of these studies have been carried out phosphate HHDMA-modified Pd nanoparticles during a three-phase continuous-flow MBY using Pd-based catalysts, where the metal particles were supported on a large variety of hydrogenation in relatively low pressure and temperature ranges (1–8 bar, 30–90 ◦C) [15]. materials. YieldsPromising of 89% resultsand 92% were were also reached obtained in capillary for the isolated microreactors Pd atoms using confined bimetallic into the six-fold Pd25Zn75 [11] and pure Pd nanoparticles [12] both supported on TiO2 and using methanol cavities of mpg-C3N4, in similar conditions. This single-site Pd catalyst showed higher as the solvent.activity Non-negligible than conventional values were heterogeneous obtained by Kundra catalysts et andal., in >90% a 3D ofprinted the selectivity cat- toward alytic static mixer.MBE [In16 ].a solution of 30% isopropanol and 70% water, with colloidal palla- dium on titanium silicate as a catalyst [13], 96% conversion and 91% alkene selectivity Furthermore, Pd supported on MgO, CeO2, ZnO and Al2O3 and bimetallic Pd–Zn were achieved at a moderate pressure of 4 bars and a relatively high temperature of 100 supported on Al2O3 were investigated for gas-phase 2-methyl-3-butyn-2-ol hydrogena- °C. On the other hand, in the same study, the performance was much lower when using tion [5]. Pd/ZnO and Pd–Zn/Al2O3 exhibited improved selectivity (c.a. 90%) as compared Lindlar catalyst.to the MBE other selectivity catalysts. over The 90% enhancement was shown wasin Al explained2O3-coated by metallic the modification monolithic of electronic reactors featuringproperties hybrid of hybrid Pd by electronhexadecyl(2-hydroxyethyl)dimethyl transfer from Pd to Zn and formationammonium of dihy- Pd–Zn alloy that drogenphosphateblocks HHDMA-modified unselective active sites.Pd nanoparticles during a three-phase continuous- flow MBY hydrogenationThe latter in revealsrelatively the low importance pressure ofand metal-support temperature interactionranges (1–8 andbar, the30– pretreatment 90 °C) [15]. Promisingmethod. Higherresults were activity also of obta Pd–Zn/Alined for2 theO3 asisolated compared Pd atoms to Pd/ZnO confined while into maintaining the six-fold cavitieshigh selectivity of mpg-C3 toN4 MBE, in similar was explained conditions. by This the single-site effect of hydrogen Pd catalyst spillover showed in the case of higher activityalumina than conventional supported catalyst heterogeneous [5]. Moreover, catalysts Pd/Al and2 O>90%3 catalytic of the performanceselectivity to- for the alkane ward MBE [16].isomerization strongly depends on the pretreatment conditions [17–20]. To the best of our Furthermore,knowledge, Pd supported although on Pd/Al MgO,2O 3CeOhas2, been ZnO commonly and Al2O studied3 and bimetallic in the MBY Pd–Zn hydrogenation in supported onflow Al2O mode3 were [ 5investigated,15] and in batch for gas-phase systems [2-methyl-3-butyn-2-ol21], the influence of this hydrogenation phenomenon has not been [5].