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Dimethylcarbonate-assisted ring-opening of biobased valerolactones with methanol Alessio Caretto, Marco Bortoluzzi, Maurizio Selva, and Alvise Perosa ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.6b01863 • Publication Date (Web): 23 Aug 2016 Downloaded from http://pubs.acs.org on August 25, 2016
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Dimethylcarbonate-assisted ring-opening of biobased valerolactones with methanol Alessio Caretto, Marco Bortoluzzi, Maurizio Selva, Alvise Perosa* Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’ Foscari Venezia, Via Torino 155, 30172 Venezia Mestre, Italy
*E-mail:
[email protected]. Keywords: dimethylcarbonate, gamma-valerolactone, methanolysis, ring-opening
ABSTRACT
The methanolysis reaction of renewable γ-valerolactone and α-methyl-γ-valerolactone in the presence of dimethylcarbonate and under acid conditions can be tuned to yield selectively each of three acyclic bio-based products: 4-hydroxy-methylpentanoate 1, 4-methoxy-methylpentanoate 2 and methyl-pent-3-enoate 3. The reaction was studied in batch and in continuous flow and a reaction mechanism based on experimental and computational evidence was proposed. The protocol is based on a set greener chemical technologies and was implemented in continuous-flow.
INTRODUCTION In a previous paper, the base-catalyzed α-alkylation of bio-derived lactones with dialkyl carbonates was described.1 Therein, new green chemical technologies based on the use of dialkylcarbonates were used for the upgrading of bio-basedγ-butyrolactone (GBL), γ-valerolactone 1 ACS Paragon Plus Environment
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(GVL) and δ-valerolactone (DVL), with a view of demonstrating new chemical pathways for their catalytic transformation into new alkylated derivatives. The tunable reactivity and the low toxicity of dialkylcarbonates, particularly of dimethyl-, diethyl- and dibenzyl-carbonate (ROCO2R; R = Me, Et, CH2Ph; DMC, DEC and DBnC, respectively), were key for their successful use as green reagents in place of hazardous alkylating reagents such as dialkyl-sulfates and alkyl halides.2 By operating under basic catalysis the lactones and the dialkylcarbonates yielded an array of new biobased molecules of interest in the biorefinery scheme. Along with ring-functionalization, the above mentioned bio-based lactones can however also undergo ring-opening to yield interesting products bearing a hydroxyl- (R’ = H) or alkoxy- (R’ = e.g. CH3, CH2CH3, …) functionality as shown in scheme 1.
Scheme 1. Ring opening of a generic lactone to yield the corresponding acyclic derivative. For example, if R’ = CH3, the resulting 4-methoxy-butanoyl- and 5-methoxy-pentanoyl- moieties are fragments of biologically active molecules, such as: antibiotics,3-4 prostaglandins and their antagonists,5-7 analgesics,8 bronchodilators,9-10 antiarrhythmics,11 and flavorings12. In addition, alkoxyesters derived by ring-opening of GVL such as the ones depicted in scheme 1 have stimulated interest as bio-oxygenated solvents;13 while GVL-derived pentenoates have been considered as synthons for monomers.14-15 While 4-hydroxy esters are readily accessible via alkaline hydrolysis as shown in scheme 1, on the contrary the preparation of the corresponding 4-alkoxyderivatives by alkaline alcoholysis is not trivial due to selectivity issues. Thus, GVL ring-opening can be accomplished by alkaline hydrolysis followed by methylation with toxic dimethyl sulfate (DMS) to yield 42 ACS Paragon Plus Environment
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methoxypentanoic-methylester: CH3OCOCH2CH2CH(OCH3)CH3.16 A slightly safer alternative is the acid-catalyzed lactone methanolysis mediated by trimethylorthoformate (TMOF) shown in scheme 2,17 that operates under acidic conditions and yields selectively the methoxy-esters. The mechanism of such reactions involves a [CH(OMe)2]+ cation generated by TMOF in the presence of an acid, as shown in scheme 2. While in principle the lactone can be activated towards nucleophilic methanolysis either by H+ or by [CH(OMe)2]+, experimental results indicate that the latter carbocation probably better coordinates the lactone carbonyl oxygen giving the adduct [CH(OMe)2GVL]+, thus making the C4 carbon the preferential site of attack respect to the C1 carbonyl due to steric reasons.
Scheme 2. Mechanism proposed by King for the synthesis of 4-methoxy butanoate from GBL mediate by TMOF.17 In the present work we recognized a parallel between TMOF and DMC, not only because both are methylating reagents,18 but also because one could envisage a similar behavior in forming a carbocation species in the presence of an acid as shown in scheme 3.
Scheme 3. Possible reactions of TMOF and DMC with a Brønsted acid. 3 ACS Paragon Plus Environment
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However, few studies deal with the reactivity of DMC under acidic conditions and those few are limited to its activation in transesterification reactions.19 Our goal was therefore to understand whether DMC could have a role in directing the regioselectivity of the methanolysis of lactones under Brønsted acidity similar to that of TMOF. GVL was chosen as a model reagent due to its interest as a bio-mass derivative and because its methanolysis can yield two regioisomers: 4-hydroxy-methylpentanoate, 1 and 4-methoxymethylpentanoate 2. Once determined that the ring-opening methanolysis of the lactones could be conducted regioselectively in the presence of a Brønsted acid we extended the protocol to a homogeneous Lewis acid such as scandium triflate in order to support our mechanistic hypothesis and to set the stage for continuous flow operation in the presence of heterogeneous acid catalysts.
EXPERIMENTAL SECTION All chemicals were reagent grade and were used as received. Analytical details are included in the supporting information file. Batch conditions Batch reactions at high temperature were performed in stainless steel autoclaves with an internal volume of 120 or 220 ml, equipped with a pressure gauge and thermocouple. Heating was provided by means of an electric oven powered by a thermoregulator and controlled by a thermocouple. In a typical high temperature reaction, GVL (1.0 ml, 10.49 mmol), PTSA (140 mg, 0.81 mmol), MeOH and DMC were combined in a steel autoclave. A set of different GVL/CH3OH/DMC molar ratios were tested: 1/30/0, 1/15/1, 1/15/10, 1/10/10, 1/2/10 and 1/0/30, respectively (table 1 and table S2). The internal volume was purged with nitrogen and the mixture was then heated at 150 °C under magnetic stirring (600 rpm) for the desired time. After cooling, the autoclave was vented, a sample was diluted with Et2O and analyzed by GC/MS. Continuous flow setup 4 ACS Paragon Plus Environment
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Continuous-flow (CF) reactions were performed by feeding the reaction mixture by means of an HPLC pump through a stainless steel tubular plug-flow reactor packed with the desired catalyst, thermostated inside a GC oven and equipped with a back pressure regulator (further details are given in the supporting information). Preparation of the catalysts Acidic alumina S (Riedel da Häen) was charged into the plug-flow reactor and heated (100 °C 2h; 250 °C 6h) in a flow of nitrogen (15 mL min-1). The dried alumina could be stored at 70 °C under vacuum. The HY zeolite was prepared by calcination of zeolite NH4Y (Sigma-Aldrich) in a quartz tube at 500 °C for 5 hours in a flow of dry air (25 mL min-1; downwards). The HY zeolite could be stored at 70 °C under vacuum. Reaction products The organic reaction products were analysed by 1H-NMR (400 MHz) and GC/MS and the structure confirmed by comparison with authentic samples. Methyl 4-hydroxy-pentanoate (1) The title compound was identified by comparison with a commercial standard. 1
H NMR (400 MHz, CDCl3) δ 3.83 (m, 1H), 3.68 (s, 3H), 2,55 (m, 2H), 1.74 (m, 2H), 1.21 (d,
3H). Mass spectrum, m/z (Irel, %): 132 (M+,
