Development of a green scalable route toward the synthesis of bio-based 2-pyrones

2-Pyrones are molecules that gained significant attention in the field of medicine and synthetic chemistry. They are broadly present in nature, where they play an important role in the defense mechanisms of the organisms in which they are present. Due to their unique structure, 2-pyrones hold immense potential both for the development of pharmacologically active compounds and as building blocks in synthetic chemistry; for these reasons those molecules have attracted researcher's attention during the past decade. In this work, we present the synthesis optimization of bio-based 2-pyrones starting from bio sourced galactaric acid by means of a statistical design of experiment, its scale up from 500 mg to 100 g, the solvent recycling to make the reaction greener as well as the synthesis of galactaric acid from galactose

Development of a flow process for an easy and fast access to 2-pyrone derivatives

2-Pyrones are compounds widely present in nature and they represent interesting building blocks both in medicinal and synthetic chemistry. Due to their peculiar pharmacological activity and structure, they have attracted much attention during the last decades and several protocols for their synthesis have been developed. In this work we propose the synthesis of bio-sourced 2-pyrones, exploiting continuous-flow conditions for an easy, sustainable and fast access to these important molecules

Sustainable Synthesis of N-Alkyl-Pyrrolecarboxylic and Pyrrolepyrazinones Derivatives from Biosourced 3-Hydroxy-2-pyrones and Amines

Pyrroles are important compounds present in biological systems, used for drug synthesis and in material chemistry. A typical strategy for the pyrrolic ring formation is centered on the Paal−Knorr reaction, where 1,4-dicarbonyl compounds react with amines giving N-substituted pyrrole derivatives. Often, the main problem of this approach is the availability of the appropriate carbonyl compounds. Here, we report a sustainable synthesis of N-substituted pyrrole carboxylic acid derivatives by the reaction of primary amines and 3-hydroxy-2-pyrones. These last compounds can easily be prepared using renewable sources and show the property to be masked 1,4-dicarbonyl compounds that are able to react efficiently with amines to form substituted pyrrolic rings. The reactions can be performed under sustainable conditions without solvents at 50−75 °C or in basic water−methanol solutions at room temperature, obtaining symmetric and asymmetric pyrroles from good to high yields. Moreover, dihydropyrrolepyrazinone derivatives can easily be prepared in high yields by the reaction of 3-hydroxy-2-pyrones and ethylenediamine

Structural features of neat 5-hydroxymethylfurfural (HMF) in the liquid state

Here we investigate the local structural organization in liquid neat 5-hydroxymethylfurfural (HMF) by the synergic use of high energy X-ray scattering, NMR spectroscopy and molecular dynamics simulations, providing atomistic insight into the correlations that characterise HMF liquid state. HMF has been acknowledged as one of the “sleeping giants” among those renewable compounds, with yet underexploited market potential. It can be obtained from renewable carbohydrate sources via a few consecutive steps and, due to its different functional groups, it can be potentially transformed into a plethora of compounds. An adequate knowledge of the driving interactions into its liquid state can be of fundamental relevance in individuating successful solvents, where HMF can be dissolved, extracted and treated to deliver new compounds. As such, this study has then the potential to provide new, sustainable routes in HMF manipulation, alternatively to current methods. The X-ray scattering validated MD study reveals the existence of a distinct π–π stacking arrangement, characterising the mutual ordering between neighbour HMF molecules. Further correlations involve hydrogen bonding between aldehyde and hydroxyl oxygen and hydroxyl hydrogen. Furthermore, indication of the existence of OH⋅⋅⋅π hydrogen bonding interaction has been detected. An NMR strategy has been applied to confirm the existence of these mutual interactions, identifying the associated structural motifs. These findings underscore the complex and heterogeneous nature of the structural organization of liquid HMF

Synthesis of Functionalized Aromatic Carboxylic Acids from Biosourced 3Hydroxy-2-pyrones through a Base-Promoted Domino Reaction

Nowadays, the use of biomass derived synthons as precursor of aromatic products is an important research topic in green chemistry. In particular, Diels–Alder protocol has been applied in the construction of valuable aromatic derivatives such as terephthalic acid and esters using muconic acid and 2-pyrones as diene components. In this context, we now propose the use of 3-hydroxy-2-pyrones, prepared from galactaric acid, as building block for the synthesis of functionalized aromatic carboxylic acids. Our protocol consists in a base promoted domino reaction in which 2-pyrones and electron-poor alkenes lead directly to the aromatic derivatives preserving all the carbon atoms. High yields are obtained by using small amounts of solvent, in neat conditions and in a water biphasic system, typically at 50 °C. The reaction proceeds through a Diels–Alder cycloaddition followed by aromatization reaction with elimination of water. The aromatization represents a key step and a possible reaction mechanism is propose

Synthesis of Functionalized Aromatic Carboxylic Acids from Biosourced 3-Hydroxy-2-pyrones Through a Base Promoted Domino Reaction

Nowadays, the use of biomass derived synthons as precursor of aromatic products is an important research topic in green chemistry. In particular, Diels–Alder protocol has been applied in the construction of valuable aromatic derivatives such as terephthalic acid and esters using muconic acid and 2-pyrones as diene components. In this context, we now propose the use of 3-hydroxy-2-pyrones, prepared from galactaric acid, as building block for the synthesis of functionalized aromatic carboxylic acids. Our protocol consists in a base promoted domino reaction in which 2-pyrones and electron-poor alkenes lead directly to the aromatic derivatives preserving all the carbon atoms. High yields are obtained by using small amounts of solvent, in neat conditions and in a water biphasic system, typically at 50 °C. The reaction proceeds through a Diels–Alder cycloaddition followed by aromatization reaction with elimination of water. The aromatization represents a key step and a possible reaction mechanism is propose