Greener and Sustainable Applications of Phosphorous and Sulfur Ylides

The present review highlights relevant recent examples (2013-2018) of sustainable synthetic reactions involving phosphorus and sulfur ylides. These examples include catalytic, halide- and base-free Wittig olefination reactions and P-ylides as CO2 activators. They also include sustainable protocols for the synthesis of S-ylides and recent applications of these C1 synthons as carbene precursors and in selected rearrangement reactions

Ionic liquids as transesterification catalysts: Applications for the synthesis of linear and cyclic organic carbonates

The use of ionic liquids (ILs) as organocatalysts is reviewed for transesterification reactions, specifically for the conversion of nontoxic compounds such as dialkyl carbonates to both linear mono-transesterification products or alkylene carbonates. An introductory survey compares pros and cons of classic catalysts based on both acidic and basic systems, to ionic liquids. Then, innovative green syntheses of task-specific ILs and their representative applications are introduced to detail the efficiency and highly selective outcome of ILs-catalyzed transesterification reactions. A mechanistic hypothesis is discussed by the concept of cooperative catalysis based on the dual (electrophilic/nucleophilic) activation of reactants

Continuous-Flow O-Alkylation of Biobased Derivatives with Dialkyl Carbonates in the Presence of Magnesium-Aluminium Hydrotalcites as Catalyst Precursors

The base-catalysed reactions of OH-bearing biobased derivatives (BBDs) including glycerol formal, solketal, glycerol carbonate, furfuryl alcohol and tetrahydrofurfuryl alcohol with nontoxic dialkyl carbonates (dimethyl and diethyl carbonate) were explored under continuous-flow (CF) conditions in the presence of three Na-exchanged Y- and X-faujasites (FAUs) and four Mg\u2013Al hydrotalcites (HTs). Compared to previous etherification protocols mediated by dialkyl carbonates, the reported procedure offers substantial improvements not only in terms of (chemo)selectivity but also for the recyclability of the catalysts, workup, ease of product purification and, importantly, process intensification. Characterisation studies proved that both HT30 and KW2000 hydrotalcites acted as catalyst precursors: during the thermal activation pre-treatments, the typical lamellar structure of the hydrotalcite was broken down gradually into a MgO-like phase (periclase) or rather a magnesia\u2013alumina solid solution, which was the genuine catalytic phase

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Green Reactions and Technologies for Biomass Valorisation

This research project has focussed on the upgrading of biomass derivatives, particularly glycerol derivatives and lignin, to higher added-value chemicals by means of green and sustainable technologies. The experimental work was divided into three main areas: i) Upgrading of glycerol and furan bio-based derivatives. Continuous-flow alkylation reactions. An innovative alkylation protocol was implemented using dialkyl carbonates as alkylating agents under continuous-flow conditions. In the presence of different classes of catalysts, Na-exchanged Y- and X-faujasites and Mg-Al hydrotalcites, functionalised bio-based alcohols and dialkyl carbonates were activated preferentially towards O-alkylations over the competitive transesterifications and other side-reactions. Synthesis of symmetrical dialkyl carbonates. s-DAlCs are of great interest as eco-friendly solvents and intermediates. Carbonate interchange reaction strategies have been investigated in this Thesis and a CF-protocol for the disproportionation of four different methyl alkyl carbonates was optimised, using Mg-Al hydrotalcites as heterogeneous catalysts. ii) Catalytic depolymerisation of Kraft lignin. Lignocellulosic biomass has been proposed as one renewable feedstock to supplement dwindling fossil reserves. In this Thesis, the catalytic depolymerisation of Kraft lignin, which constitutes 25-30% of lignocellulosic biomass, in supercritical ethanol was explored in the presence of eight Mo2C- and MoS2-based catalysts, affording aromatic yields as high as 506 mg/g lignin, amongst the highest yields reported to date. iii) Cleaning up fuels. Nitrogen-based compounds are commonly found in biocrude oils generated from biomass. Since they interfere with traditional refining methods they need to be removed prior to their integration into the supply chain. In this thesis, twelve ionic liquids based on common cations and anions were synthesised and used for the selective extraction of archetypical N-compounds from a model oil

Dimethylcarbonate for the catalytic upgrading of bio-based derivatives

In the past three decades, the use of dialkyl carbonates (DAlCs) as greener solvents and as non-toxic reagents has gradually improved. For instance, dimethylcarbonate (DMC) has widely be employed as non-toxic reagent for catalytic alkylation, carboxyalkylations and transesterification processes. Starting from different bio-based chemicals it is possible to obtain a wide variety of derivatives depending on the type of catalyst employed. Inorganic catalysts including alkaline carbonates, faujasites, and hydrotalcites were proved to be active towards the selective alkylation of glycerol-based derivatives [1], [2], whereas organic catalysts (ionic liquids, ILs) promote, starting from diols, the synthesis of cyclic organic carbonates [3]. Asymmetric methyl carbonates can be obtained within a catalyst-free protocol from simple alcohols [4]. With solid heterogeneous catalysts, it has been improved the feasibility to work under continuous flow (CF) conditions

CHAPTER 14. CO2 and Organic Carbonates for the Sustainable Valorization of Renewable Compounds

The present chapter collects and describes representative examples from the current literature on the use of CO2 and Organic Carbonates for the Sustainable Valorization of Renewable Compounds. For the reader's convenience, after an introductory section aimed at highlighting both the potential and challenges associated with the chemical upgrading of renewable compounds, topics are organized in three parts surveying the following subjects: (i) catalytic and photocatalytic routes for both the reduction of CO2 and use of CO2 for the carboxylation of C(sp3)–H bonds and bio-based epoxides, and the methylation of amines; (ii) model strategies for carboxylation and alkylation reactions mediated by non-toxic dialkyl carbonates for the valorization of bio-based platform chemicals including glycerol, succinate, and dimethyl-2,5-furandicarboxylate, and renewable lactones, as well as natural polysaccharides (cellulose, starch, and chitin) and lignin; (iii) the sustainable synthesis of bio-polycarbonates and bio-polyurethanes via sequential transesterification/polycondensation reactions with dialkyl carbonates and cycloadditions of CO2 into renewable epoxides

Methyltriphenylphosphonium Methylcarbonate, an All-In-One Wittig Vinylation Reagent

The methyltriphenylphosphonium methylcarbonate salt [Ph3PCH3][CH3OCO2], obtained directly by quaternarization of triphenylphosphine with dimethylcarbonate, is a latent ylide that promotes Wittig vinylation of aldehydes and ketones. Alkenes are obtained simply by mixing [Ph3PCH3][CH3OCO2] and the carbonyl and heating in a solvent (no base, no halides, and no inorganic byproducts). Deuterium exchange experiments and the particularly short anion-cation distance measured by XRD in [Ph3PCH3][CH3OCO2] allowed to explain the nature and reactivity of this species. Green chemistry metrics (atom economy, mass index, environmental factor) indicate that this vinylation procedure is more efficient than comparable ones. Deuterated [Ph3PCD3][CH3OCO2] promoted the synthesis of deuterated olefins

Two-step Synthesis of Dialkyl Carbonates through Transcarbonation and Disproportionation Reactions Catalyzed by Calcined Hydrotalcites

A two-step methodology was implemented to prepare dialkyl carbonates from both primary and secondary alcohols, including glycerol acetals, tetrahydrofurfuryl alcohol and cyclohexanol. Accordingly, alcohols were initially subjected to a batch transcarbonation (carbonate interchange) reaction with the non-toxic dimethyl carbonate (DMC), providing the corresponding asymmetrical methyl alkyl carbonates (ROCO2Me). These compounds were then used as reactants for a continuous-flow (CF) disproportionation reaction, producing the corresponding symmetrical dialkyl carbonates (ROCO2R). Although transcarbonation and dismutation took place at different operating temperatures (90 and 180-275 °C, respectively), both reactions were catalyzed by the same heterogeneous Mg/Al mixed oxides catalyst, obtained upon calcination of commercially available hydrotalcites (HTs). Yields and selectivities for methyl alkyl carbonates were excellent, in the range of 93-96% and 95-98%, respectively. CF-disproportionation reactions were strongly affected by the nature/structure of reactants, nevertheless, they provided the corresponding dialkyl carbonates with selectivities and productivities up to 92% and 164 mgprod∙(gcat∙min)-1, respectively. Overall, the reported methodology displays attractive sustainability features, including a straight-forward upgrade of biomass derivatives, development of a continuous-flow intensified process, improved catalyst recycle and products’ purification, while disclosing stimulating perspectives for further investigations on the reaction mechanism and on the role of HTs as catalyst precursors for the synthesis of organic carbonates