Furans represent one of the most important classes of intermediates in the conversion of non-edible lignocellulosic biomass into bio-based chemicals and fuels. At present, bio-furan derivatives are generally obtained from cellulose and hemicellulose fractions of biomass via the acid-catalyzed dehydration of their relative C6-C5 sugars and then converted into a wide range of products. Furfural (FUR) and 5-hydroxymethylfurfural (HMF) are surely the most used furan-based feedstocks since their chemical structure allows the preparation of various high-value-added chemicals. Among several well-established catalytic approaches, hydrogenation and oxygenation processes have been efficiently adopted for upgrading furans; however, harsh reaction conditions are generally required. In this review, we aim to discuss the conversion of biomass derived FUR and HMF through unconventional (transfer hydrogenation, photocatalytic and electrocatalytic) catalytic processes promoted by heterogeneous catalytic systems. The reaction conditions adopted, the chemical nature and the physico-chemical properties of the most employed heterogeneous systems in enhancing the catalytic activity and in driving the selectivity to desired products are presented and compared. At the same time, the latest results in the production of FUR and HMF through novel environmental friendly processes starting from lignocellulose as well as from wastes and by-products obtained in the processing of biomass are also overviewed.

Recent catalytic routes for the preparation and the upgrading of biomass derived furfural and 5-hydroxymethylfurfural

Biorefinery roadmap based on catalytic production and upgrading 5-hydroxymethylfurfural

In order to optimize the production of biobased platform chemicals, such as 5-hydroxymethylfurfural (HMF) and levulinic acid (LA), from biomass and sugars, reaction conditions have to be optimized. This article assesses the impact of acidity on the kinetic parameters of the hydrothermal conversion of fructose at 150 °C. The reaction parameters were varied in time (5–180 min), acid (NaHSO4, H3PO4, citric acid, and formic acid), and acid concentration (0.016 to 1.6 mol/l). The experimental data were evaluated with a novel kinetic model that includes the formation of HMF, LA, and humins. While it was expected that the dehydration rate of fructose to HMF and rehydration rate of HMF to levulinic acid depend linearly on the proton concentration, the results show that there is actually an exponential relationship. This can be explained by the participation of the acid rest ion in the dehydration and rehydration reactions. In contrast, the humin formation rate depends linearly on the proton concentration, and also, the sensitivity of this relationship is rather low. This clarifies why high acid concentrations or proton concentrations, respectively, increase the formation of LA to an expense of the humin formation.

https://link.springer.com/content/pdf/10.1007/s13399-019-00507-0.pdf

Kinetic study on the impact of acidity and acid concentration on the formation of 5-hydroxymethylfurfural (HMF), humins, and levulinic acid in the hydrothermal conversion of fructose

For the first time, the heterogeneous calcined forms of chromium loaded USY, ZSM-5 and Beta zeolites were studied for the synthesis of HMF from glucose and cellulose in different solvents such as 1-butyl-3-methylimidazolium chloride (BMIMCl) and dimethyl sulfoxide (DMSO). Catalysts were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, inductive coupling plasma-mass spectrometry and temperature programmed desorption (NH3-TPD). It was found that calcined forms of chromium-zeolites provide better HMF yield in (BMIMCl) ionic liquid than chromium-free zeolites. The 58.8% and 54.5% HMF yields from glucose and 34.1% and 34.3% HMF yields from cellulose were obtained at 130 °C after 60 min in BMIMCl ionic liquid with Cr-Beta (SiO2/Al2O3 = 28) and Cr-USY (SiO2/Al2O3 = 6) zeolites, respectively. 35% HMF yield was achieved with heterogeneous Cr-USY (SiO2/Al2O3 = 6) zeolite at 160 °C after 90 min in DMSO. However, HMF yield from cellulose was not observed in DMSO. Although chromium leaching from catalyst occurred in BMIMCI solvent, no loss of catalytic activity and no chromium leaching from catalyst was observed in DMSO for five times recycling reactions. It can be said that DMSO is highly suitable solvent for easily separable heterogeneous Cr-USY catalyst for glucose to HMF conversion.

Heterogeneous Cr-zeolites (USY and Beta) for the conversion of glucose and cellulose to 5-hydroxymethylfurfural (HMF)

Despite their desirable attributes, boronic acids have had a minimal impact in biological contexts. A significant problem has been their oxidative instability. At physiological pH, phenylboronic acid and its boronate esters are oxidized by reactive oxygen species at rates comparable to those of thiols. After considering the mechanism and kinetics of the oxidation reaction, we reasoned that diminishing electron density on boron could enhance oxidative stability. We found that a boralactone, in which a carboxyl group serves as an intramolecular ligand for the boron, increases stability by 104-fold. Computational analyses revealed that the resistance to oxidation arises from diminished stabilization of the p orbital of boron that develops in the rate-limiting transition state of the oxidation reaction. Like simple boronic acids and boronate esters, a boralactone binds covalently and reversibly to 1,2-diols such as those in saccharides. The kinetic stability of its complexes is, however, at least 20-fold greater. A boralactone also binds covalently to a serine side chain in a protein. These attributes confer unprecedented utility upon boralactones in the realms of chemical biology and medicinal chemistry.

https://www.pnas.org/content/pnas/118/10/e2013691118.full.pdf

Boronic acid with high oxidative stability and utility in biological contexts.

5-Hydroxymethylfurfural (HMF), which can be synthesized from hexose sugars without rearrangement of their carbon framework, is a key platform chemical that is readily convertible into fuels and chemicals that are now derived from petroleum. Methods to convert glucose, which is readily accessible from cellulose, to HMF typically rely on toxic heavy metals or harsh acidic conditions and often give low yields or low selectivity. Here, we report on a mild, efficient, and metal-free process that uses an organocatalyst, 2-carboxyphenylboronic acid, along with small amounts of chloride ion to effect the selective transformation of glucose to HMF.

/pdf/efficient-metal-free-conversion-of-glucose-to-5-uhjw03yr7l.pdf

Efficient metal-free conversion of glucose to 5-hydroxymethylfurfural using a boronic acid

Organoboron acids are stable, organic-soluble Lewis acids with potential application as catalysts for a wide variety of chemical reactions. In this review, we summarize the utility of boronic and borinic acids, as well as boric acid, as catalysts for organic transformations. Typically, the catalytic processes exploit the Lewis acidity of trivalent boron, enabling the reversible formation of a covalent bond with oxygen. Our focus is on recent developments in the catalysis of dehydration, carbonyl condensation, acylation, alkylation, and cycloaddition reactions. We conclude that organoboron acids have a highly favorable prospectus as the source of new catalysts.

Emergent Organoboron Acid Catalysts.

HIV-1 protease is an important target for pharmaceutical intervention in HIV infection. Extensive structure-based drug design led to darunavir becoming a key chemotherapeutic agent. We replaced the aniline group of darunavir with a benzoxaborolone to form BOL-darunavir. This analogue has the same potency as darunavir as an inhibitor of catalysis by wild-type HIV-1 protease and, unlike darunavir, does not lose potency as an inhibitor of the common D30N variant. Moreover, BOL-darunavir is much more stable to oxidation than is a simple phenylboronic acid analogue of darunavir. X-ray crystallography revealed an extensive network of hydrogen bonds between the enzyme and benzoxaborolone moiety, including a novel direct hydrogen bond from a main-chain nitrogen to the carbonyl oxygen of the benzoxaborolone moiety that displaces a water molecule. These data highlight the utility of benzoxaborolone as a pharmacophore.

Inhibition of HIV-1 Protease by a Boronic Acid with High Oxidative Stability.

Provided herein are boron-containing compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders.

Brian J. Graham

Papers

Boronic acid with high oxidative stability and utility in biological contexts.

Efficient metal-free conversion of glucose to 5-hydroxymethylfurfural using a boronic acid

Emergent Organoboron Acid Catalysts.

Inhibition of HIV-1 Protease by a Boronic Acid with High Oxidative Stability.

Boron-containing pharmacophore