Dimethyl isosorbide via organocatalyst N-methyl pyrrolidine: scaling up, purification and concurrent reaction pathways

Dimethyl isosorbide (DMI) is a green replacement for conventional dipolar solvents as dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) that are toxic and dangerous for human and environmental health. DMI is one of the simplest derivatives well-known bio-based platform chemical isosorbide, an anhydro sugar readily synthesised by D-sorbitol dehydration reaction. [1] The synthesis of DMI is mainly based on the etherification of bio-based platform chemical isosorbide in the presence of basic or acid catalyst employing different alkylating agent. Among them, dimethyl carbonate (DMC) is relevant thanks to its haracteristics: good biodegradability and low toxicity. [2] In this work, we report an extensive investigation on highly yielding methylation of isosorbide via DMC chemistry promoted by several nitrogen organocatalyst. [3] Reaction conditions were performed and then applied for the methylation of isosorbide epimers - isomannide and isoidide - and for preliminary scale-up test (10 g of isosorbide). Pure DMI, starting from mixture reaction, was obtained by both column chromatography and distillation at reduced pressure. Between all nitrogen used, N-methyl pyrrolidine (NMPy) demonstrated excellent behaviour as catalyst also for the one-pot conversion of D-sorbitol into DMI. Furthermore, for the first time, all seven methyl and carboxymethyl intermediates - observed during the etherification of isosorbide - were synthetized, isolated and characterised. This study allowed us to know more deeply the concurrent reaction pathways (methylation, methyl carbonylation and decarboxylation) leading to DMI and on the role played by NMPy in the methylation of isosorbide and in this way to propose a mechanism of conversion into isosorbide into DMI via DMC chemistry

5,5'(Oxy-bis(methylene)bis-2-furfural (OBMF) from 5-hydroxymethyl-2-furfural (HMF): a systematic study for the synthesis of a new platform molecule from renewable substances

The continued exploitation and depletion of fossil fuels has prompted the scientific community to search for more sustainable and environmentally friendly alternatives. In the last decade, the synthesis of biomass-derived chemicals has become a priority to boost the transition from refinery to biorefinery. Sugars are an extremely abundant bio-resource in nature; even today, one of the most studied reactions is the synthesis of 5-hydroxymethyl-2-furfural (HMF). This compound is considered extremely important for biorefinery because of its wide range of possible applications (pharmaceutical, biofuels, polymer precursors, surfactants). However, it has been observed, during the spontaneous degenerative process of HMF, the formation of a compound that could be equally important 5,5'-[oxybis(methylene)]bis-2-furfural (OBMF). The synthesis of OBMF is scarcely reported in the literature, only in recent years interest in this dimer of HMF has emerged for its possible applications in industry. Good yield values of OBMF are reported in the literature from HMF (Figure 1) in the presence of an acid catalyst; however, the solvents used are the most common halogenated and/or aromatic solvents, known to be toxic. The objective of this work was to find a viable synthetic route to access OBMF without having to resort to the use of such solvents and, in addition, utilize already commercially available and inexpensive acid catalysts. Through smallscale optimizations, the best solvent was found to be dimethyl carbonate;4 In addition, two heterogeneous acid catalysts - Purolite 269 and ferric sulfate (Fe2(SO4)3) - showed excellent efficiency in promoting the HMF etherification reaction with quantitative yields (> 90%). Subsequently, a scale-up of the reaction was carried out, obtaining OBMF with an isolated yield of 81%. Given the excellent results obtained, this work can be a starting point to undertake the study of new synthetic methodologies for this molecule such as continuous flow reactions of which the literature is lacking

Evaluating the Impacts of Alcohol-Based Solutions on Silk: Chemical, Mechanical and Wettability Changes before and after Artificial Ageing

Due to the COVID-19 pandemic, since 2020, alcohol-based sanitisers have been frequently used in museums and historic sites. Although they provide a safer environment for visitors, the impact of the (components in) sanitisers on the cultural heritage on open display is still uncertain. The current study investigated the effects of ethanol and isopropanol solutions on silk artefacts specifically in relation to possible mechanical changes and to their long-term impact based on artificial ageing. Thus, samples from three modern silk fabrics were treated through spraying and immersion with six solutions, two of which contained benzalkonium chloride (BZK), a surfactant suggested by Italian national guidelines in the formulation of sanitisers for museums. The impact of the treatment was studied from a chemical perspective, i.e., through spectroscopic techniques, and considering changes in the mechanical strength through uniaxial tensile testing. In addition, water wettability was measured. To study whether the contact with the solutions can affect the degradation path of silk, after the treatment, samples were exposed to light ageing and were stored at medium and high RH, i.e., 55% and 80%. Furthermore, treated and untreated silk textiles were placed in the Museum of Palazzo Mocenigo (Venice) to define the behaviour in an actual museum environment. The results show that, even when silk is immersed in the solutions for 180 min, no relevant chemical and physical changes can be observed on silk fibres. Variations noted at the end of the light ageing occurred regardless of the treatments with the solutions, so they are not affected by the contact with sanitisers. Nevertheless, when treating the samples (also through spraying) with solutions containing BZK, the surfactant is adsorbed by the textile. Once adsorbed, BZK significantly increases the water wettability of silk, causing a persistent modification of the property as also observed at the end of the ageing and in situ tests

Multi gram scale synthesis of HMF and comparative environmental evaluation

5-Hydroxymethylfurfural (HMF) is a bio-based platform chemical that can be used as building block to produce complex and useful compounds with diverse applicability, in particular, bio-based polymers, materials and fuels [1], [2]. Even though HMF synthesis holds promise for a greener future, with the current state of technology the high production cost limits its competitiveness at an industrial scale[1]. In this project our main goal is to develop an optimized procedure for the synthesis of HMF that will allow us to perform scale-up reactions with competitive yields with a green mindset. The synthesis of HMF from the dehydration of D-fructose, already investigated by our research group[2], was performed with a heterogeneous acid catalyst using various conditions in different settings: autoclave, sonificator and microwave oven. The best results were obtained employing a stainless-steel autoclave which allowed a large scale HMF production using up to forty grams of D-fructose as starting material. The final product was recovered from the crude mixture and purified by a custom-made crystallization procedure. Finally, green metrics were used to evaluate the greenness of the reaction in comparison with previously reported works[3]

performance improvements in a large scale virtualization system

This work shows the optimizations we have been investigating and implementing at the KVM virtualization layer in our research institute based on more than a year of experience in running thousands of VMs in a production environment used by several international collaborations. These optimizations increase the adaptability of virtualization solutions to demanding applications like those run in our institute (High-Energy Physics). In particular we will show what is the best solution to share storage space from an hypervisor to the virtual machines running on top of it, trying to avoid problems that modern storage cluster have. We will also show how different the performance can be comparing real and virtual machines, measuring access to computing, storage and network resources, trying to provide hints on server configuration where possible. This work has been driven by the project called Worker Nodes on Demand Service (WNoDeS), developed by INFN, a framework designed to offer local, grid or cloud-based access to computing and storage resources, preserving maximum compatibility with existing computing center policies and work-flows

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Multigram Synthesis of Pure HMF and BHMF

5-Hydroxymethylfurfural (HMF) is a bio-based platform chemical that can be used as a building block to produce several compounds with diverse applications. Even though HMF synthesis holds promise for a greener future, the current state of technology and the high production cost limit its competitiveness on an industrial scale. In this prospect, we have developed a multigram-scale procedure for HMF by reacting D-fructose with Purolite CT275DR-an acidic resin-in a dimethyl carbonate (DMC)/tetraethyl ammonium bromide (TEAB) biphasic system. Reactions performed in an autoclave for 2 h at 110 degrees C using up to 40 gram of D-fructose resulted in an overall HMF yield of 70%. HMF was purified by a custom-made procedure leading to ca 50% of the pure crystalline product; meanwhile, the residual HMF-rich oil was directly reduced to bis(hydroxymethyl)furan (BHMF). Green metrics and the Ecoscale algorithm were used to evaluate the sustainability of the herein-proposed procedure in comparison with works

Revitalizing Collective Resources in Mountain Areas Through Community Engagement and Knowledge Cocreation

The ongoing global and large-scale changes in markets, demographics, and use of resources are impacting mountain peoples and regions. In mountain areas, resources have been governed through community-based systems for resource management for centuries, ensuring stewardship and local decision-making over the resources. Due to the importance of such systems to mountain societies, there is a need to understand local effects of global changes and reconfigure community-based resource management (CRM) to meet local needs while tackling global challenges. Changes include biodiversity loss and the climate crisis, as well as increasing social and economic disparities. Studies on the role of knowledge cocreation in the process of CRM innovation in response to ongoing changes in mountain social–ecological systems are missing. This study aimed to explore the reconfigurations that enable CRM to foster sustainable development and thriving communities. The study focused on an intervention promoting community entrepreneurship in community-based tourism for the revitalization of collective resources in 2 mountain communities in Northern Italy. We adopted a transdisciplinary approach and a research action methodology to codesign the interventions and research. Data from focus groups, a survey, participatory activities, interviews, and participant observation were collected and analyzed using a qualitative content analysis method. Results show that emerging reconfigurations in CRM include recognition of new values and uses of collective resources, inclusion of new stakeholders, and innovation of the organizational model, shifting the perspective from resource management to resource governance. The study recommends striking a balance between pushing innovation and increasing power imbalances. It is important to pay attention to the inclusivity of the process and to avoid excessive commodification of resources