Catalytic Production of Levulinic Acid (LA) from Actual Biomass.

Catalytic conversion of actual biomass to valuable chemicals is a crucial issue in green chemistry. This review discusses on the recent approach in the levulinic acid (LA) formation from three prominent generations of biomasses. Our paper highlights the impact of the nature of different types of biomass and their complex structure and impurities, different groups of catalyst, solvents, and reaction system, and condition and all related pros and cons for this process.

Redefining biorefinery: the search for unconventional building blocks for materials.

This review discusses different strategies for the upgrading of biomass into sustainable monomers and building blocks as scaffolds for the preparation of green polymers and materials.

Morphology Tailoring of Sulfonic Acid Functionalized Organosilica Nanohybrids for the Synthesis of Biomass-Derived Alkyl Levulinates.

Morphology evolution of sulfonic acid functionalized organosilica nanohybrids (Si(Et)Si-Pr/ArSO3 H) with a 1D tubular structure (inner diameter of ca. 5 nm), a 2D hexagonal mesostructure (pore diameter of ca. 5 nm), and a 3D hollow spherical structure (shell thickness of 2-3 nm and inner diameter of ca. 15 nm) was successfully realized through P123-templated sol-gel cocondensation strategies and fine-tuning of the acidity followed by aging or a hydrothermal treatment. The Si(Et)Si-Pr/ArSO3 H nanohybrids were applied in synthesis of alkyl levulinates from the esterification of levulinic acid and ethanolysis of furfural alcohol. Hollow spherical Si(Et)Si-Pr/ArSO3 H and hexagonal mesoporous analogues exhibited the highest and lowest catalytic activity, respectively, among three types of nanohybrids; additionally, the activity was influenced by the -SO3 H loading. The activity differences are explained in terms of different Brønsted acid and textural properties, reactant/product diffusion, and mass transfer rate, as well as accessibility of -SO3 H sites to the reactant molecules. The reusability of the nanohybrids was also evaluated.

Chemical-catalytic approaches to the production of furfurals and levulinates from biomass.

The synthesis and chemistry of 5-(hydroxymethyl)furfural (HMF), 5-(chloromethyl)furfural (CMF), and levulinic acid (LA), three carbohydrate-derived platform molecules produced by the chemical-catalytic processing of lignocellulosic biomass, is reviewed. Starting from the historical derivation of these molecules and progressing through modern approaches to their production from biomass feedstocks, this review will then survey their principal derivative chemistries, with particular attention to aspects of commercial relevance, and discuss the relative merits of each molecule in the future of biorefining.

Diversity-oriented synthesis and activity evaluation of substituted bicyclic lactams as anti-malarial against Plasmodium falciparum.

BACKGROUND: Malaria remains the world's most important devastating parasitic disease. Of the five species of Plasmodium known to infect and cause human malaria, Plasmodium falciparum is the most virulent and responsible for majority of the deaths caused by this disease. Mainstream drug therapy targets the asexual blood stage of the malaria parasite, as the disease symptoms are mainly associated with this stage. The prevalence of malaria parasite strains resistance to existing anti-malarial drugs has made the control of malaria even more challenging and hence the development of a new class of drugs is inevitable. METHODS: Screening against different drug resistant and sensitive strains of P. falciparum was performed for few bicyclic lactam-based motifs, exhibiting a broad spectrum of activity with low toxicity generated via a focussed library obtained from diversity oriented synthesis (DOS). The synthesis and screening was followed by an in vitro assessment of the possible cytotoxic effect of this class of compounds on malaria parasite. RESULTS: The central scaffold a chiral bicyclic lactam (A) and (A') which were synthesized from (R)-phenylalaninol, levulinic acid and 3-(2-nitrophenyl) levulinic acid respectively. The DOS library was generated from A and from A', by either direct substitution with o-nitrobenzylbromide at the carbon α- to the amide functionality or by conversion to fused pyrroloquinolines. Upon screening this diverse library for their anti-malarial activity, a dinitro/diamine substituted bicyclic lactam was found to demonstrate exceptional activity of >85% inhibition at 50 µM concentration across different strains of P. falciparum with no toxicity against mammalian cells. Also, loss of mitochondrial membrane potential, mitochondrial functionality and apoptosis was observed in parasite treated with diamine-substituted bicyclic lactams. CONCLUSIONS: This study unveils a DOS-mediated exploration of small molecules with novel structural motifs that culminates in identifying a potential lead molecule against malaria. In vitro investigations further reveal their cytocidal effect on malaria parasite growth. It is not the first time that DOS has been used as a strategy to identify therapeutic leads against malaria, but this study establishes the direct implications of DOS in scouting novel motifs with anti-malarial activity.

Insights into the interplay of Lewis and Brønsted acid catalysts in glucose and fructose conversion to 5-(hydroxymethyl)furfural and levulinic acid in aqueous media.

5-(Hydroxymethyl)furfural (HMF) and levulinic acid production from glucose in a cascade of reactions using a Lewis acid (CrCl3) catalyst together with a Brønsted acid (HCl) catalyst in aqueous media is investigated. It is shown that CrCl3 is an active Lewis acid catalyst in glucose isomerization to fructose, and the combined Lewis and Brønsted acid catalysts perform the isomerization and dehydration/rehydration reactions. A CrCl3 speciation model in conjunction with kinetics results indicates that the hydrolyzed Cr(III) complex [Cr(H2O)5OH](2+) is the most active Cr species in glucose isomerization and probably acts as a Lewis acid-Brønsted base bifunctional site. Extended X-ray absorption fine structure spectroscopy and Car-Parrinello molecular dynamics simulations indicate a strong interaction between the Cr cation and the glucose molecule whereby some water molecules are displaced from the first coordination sphere of Cr by the glucose to enable ring-opening and isomerization of glucose. Additionally, complex interactions between the two catalysts are revealed: Brønsted acidity retards aldose-to-ketose isomerization by decreasing the equilibrium concentration of [Cr(H2O)5OH](2+). In contrast, Lewis acidity increases the overall rate of consumption of fructose and HMF compared to Brønsted acid catalysis by promoting side reactions. Even in the absence of HCl, hydrolysis of Cr(III) decreases the solution pH, and this intrinsic Brønsted acidity drives the dehydration and rehydration reactions. Yields of 46% levulinic acid in a single phase and 59% HMF in a biphasic system have been achieved at moderate temperatures by combining CrCl3 and HCl.

Solvent effect on pathways and mechanisms for D-fructose conversion to 5-hydroxymethyl-2-furaldehyde: in situ 13C NMR study.

Noncatalytic reactions of D-fructose were kinetically investigated in dimethylsulfoxide (DMSO), water, and methanol as a function of time at temperatures of 30-150 °C by applying in situ (13)C NMR spectroscopy. The products were quantitatively analyzed with distinction of isomeric species by taking advantage of site-selective (13)C labeling technique. In DMSO, D-fructose was converted first into 3,4-dihydroxy-2-dihydroxymethyl-5-hydroxymethyltetrahydrofuran having no double bond in the ring, subsequently into 4-hydroxy-5-hydroxymethyl-4,5-dihydrofuran-2-carbaldehyde having one double bond through dehydration, and finally into 5-hydroxymethyl-2-furaldehyde (5-HMF) having two double bonds. No other reaction pathways were involved, as shown from the carbon mass balance. In water, 5-HMF, the final product in DMSO, was generated with the precursors undetected and furthermore transformed predominantly into formic and levulinic acids and slightly into 1,2,4-benzenetriol accompanied by polymerization. D-glucose was also produced through the reversible transformation of the reactant D-fructose. In methanol, some kinds of anhydro-D-fructoses were generated instead of 5-HMF. The reaction pathways can thus be controlled by taking advantage of the solvent effect. The D-fructose conversion reactions are of the first order with respect to the concentration of D-fructose and proceed on the order of minutes in DMSO but on the order of hours in water and methanol. The rate constant was three orders of magnitude larger in DMSO than in water or methanol.

Alkyl levulinates as `green chemistry' precursors: butane-1,4-diyl bis(4-oxopentanoate) and hexane-1,6-diyl bis(4-oxopentanoate).

Levulinic acid derivatives are potential `green chemistry' renewably sourced molecules with utility in industrial coatings applications. Suitable single crystals of the centrosymmetric title compounds, C14H22O6 and C16H26O6, respectively, were obtained with difficulty. The data for the latter hexane-1,6-diyl compound were extracted from the major fragment of a three-component twinned crystal. Both compounds crystallize in similar-sized unit cells with identical symmetry, utilizing the same weak nonconventional attractive C-H···O(ketone) hydrogen bonds via C(4) and C(5) motifs, which expand to R(2)(2)(30) ring and C(2)(2)(14) chain motifs. Their different packing orientations in similar-sized unit cells suggest that crystal growth involving packing mixes could lead to intergrowths or twins.

Detoxification of acidic catalyzed hydrolysate of Kappaphycus alvarezii (cottonii).

Red seaweed, Kappaphycus alvarezii, holds great promise for use in biofuel production due to its high carbohydrate content. In this study, we investigated the effect of fermentation inhibitors to the K. alvarezii hydrolysate on cell growth and ethanol fermentation. In addition, detoxification of fermentation inhibitors was performed to decrease the fermentation inhibitory effect. 5-Hydroxymethylfurfural and levulinic acid, which are liberated from acidic hydrolysis, was also observed in the hydrolysate of K. alvarezii. These compounds inhibited ethanol fermentation. In order to remove these inhibitors, activated charcoal and calcium hydroxide were introduced. The efficiency of activated charcoals was examined and over-liming was used to remove the inhibitors. Activated charcoal was found to be more effective than calcium hydroxide to remove the inhibitors. Detoxification by activated charcoal strongly improved the fermentability of dilute acid hydrolysate in the production of bioethanol from K. alvarezii with Saccharomyces cerevisiae. The optimal detoxifying conditions were found to be below an activated charcoal concentration of 5%.

Nonactin biosynthesis: unexpected patterns of label incorporation from 4,6-dioxoheptanoate show evidence of a degradation pathway for levulinate through propionate in Streptomyces griseus.

The polyketide nonactin, a polyketide possessing antitumor and antibacterial activity, is produced by an unusual biosynthesis pathway in Streptomyces griseus that uses both enantiomers of the nonactin precursor, nonactic acid. Despite many studies with labeled precursors, much of the biosynthesis pathway remains unconfirmed, particularly the identity of the last achiral intermediate in the pathway, which is believed to be 4,6-diketoheptanoyl-CoA. We set out to confirm the latter hypothesis with feeding studies employing [4,5-(13)C(2)]-, [5,6-(13)C(2)]-, and [6,7-(13)C(2)]-4,6-diketoheptanoate thioester derivatives. In each case the isotopic label was incorporated efficiently into nonactin; however, at positions inconsistent with the currently accepted biosynthesis pathway. To resolve the discrepancy, we conducted additional feeding studies with a [3,4-(13)C(2)]levulinate thioester derivative and again observed efficient label incorporation. The latter result was intriguing, as levulinate is not an obvious precursor to nonactin. Levulinate, however, is known to be efficiently degraded into propionate even though the pathway for the conversion is not known. On the basis of both our levulinate and diketoheptanoate isotope incorporation data we can now postulate a pathway from levulinate to propionate that can also account for the conversion of 4,6-diketoheptanoate into levulinate in S. griseus.

Levulinic acid production from wheat straw.

Studies were carried out on the effects of temperature, acid concentration, liquid:solid ratio and reaction time on levulinic acid production from wheat straw using response surface methodology. The P-value of the coefficient for acid concentration was 0.0002, suggesting that this was highly significant. The quadratic effects of temperature and liquid:solid ratio were also significant and their P-values were <0.0001 and 0.0027, respectively. The coefficient determination (R(2)) was good for the second-order model. The optimal conditions for levulinic acid production from wheat straw were 209.3 degrees C, 3.5% acid concentration, 15.6 liquid:solid ratio and 37.6 min of reaction time resulted 19.86% yield.

Synthesis of Butyl Levulinate Based on α-Angelica Lactone in the Presence of Easily Separable Heteropoly Acid Catalysts.

A series of choline (Ch)-exchanged heteropoly acids (HOCH2 CH2 N(CH3 )3 )x H(6-x) P2 W18 O62 [abbreviated as Chx H(6-x) P2 W18 O62 , x=1-6] was synthesized and used as catalysts for the reaction of α-angelica lactone (alpha-AL) with n-butanol to form butyl levulinate (BL). The solubility of Chx H(6-x) P2 W18 O62 in the reaction mixture was temperature dependent: The catalysts were soluble under the reaction conditions and precipitated upon cooling of the reaction mixture. This facilitated recovery of the catalysts from the liquid phase. Importantly, an increase of the Ch content caused a decrease of the catalyst solubility. Catalytic activity of Chx H(6-x) P2 W18 O62 for the reaction with n-butanol appeared to be in good agreement with the concentration of Brønsted-acidic sites. The results suggest that the reaction proceeded through formation of pseudo-butyl levulinate as intermediate. Ch2 H4 P2 W18 O62 exhibited the best balance between catalytic activity and temperature-dependent solubility. The yield of BL reached 79.4 % at full conversion of alpha-AL at a moderate temperature of 75 °C in an open system. Chx H(6-x) P2 W18 O62 could be successfully reused five times without significant loss of activity.

New Insights into the Reactivity of Biomass with Butenes for the Synthesis of Butyl Levulinates.

This article reports a detailed study on the reactivity of levulinic acid and cellulose with 1-butene and iso-butene for the catalytic formation of sec- and tert-butyl levulinates. The influence of catalyst type and various solvent conditions have been investigated to assess the potential of a sustainable transformation. A very simple and efficient procedure was discovered by using reusable Amberlyst-15 in the absence of solvent to form, from levulinic acid and iso-butene, tert-butyl levulinate (70 % yield), a compound very difficult to prepare by other means. sec-Butyl levulinate (66 % yield) was obtained by using Amberlyst-15 in γ-butyrolactone as a biosourced solvent. The original procedure was also extended notably by directly using cellulose as a reactant. In the presence of a catalytic amount of H2 SO4 , it was possible to form sec-butyl levulinate (19 % yield) from 1-butene in a more efficient way than by using the alcohol as an esterifying agent.

Catalytic Conversion of Carbohydrates to Levulinate Ester over Heteropolyanion-Based Ionic Liquids.

An efficient one-pot approach for the production of levulinate ester from renewable carbohydrates is demonstrated over heteropolyanion-based ionic liquid (IL-POM) catalysts with alcohols as the promoters and solvents. The relationships between the structure, acidic strength, and solubility of the IL-POM in methanol and the catalytic performance were studied intensively. A cellulose conversion of 100 % could be achieved with a 71.4 % yield of methyl levulinate over the catalyst [PyPS]3 PW12 O40 [PyPS=1-(3-sulfopropyl)pyridinium] at 150 °C for 5 h. This high efficiency is ascribed to the reasonably high activity of the ionic liquid (IL) catalyst and reaction coupling with rapid in situ esterification of the generated levulinic acid with the alcohol promoter, which allows the insolubility of cellulose encountered in biomass conversion to be overcome. Furthermore, the present process exhibits high feedstock adaptability for typical carbohydrates and handy catalyst recovery by a simple self-separation procedure through temperature control.

Novel integrated mechanical biological chemical treatment (MBCT) systems for the production of levulinic acid from fraction of municipal solid waste: A comprehensive techno-economic analysis.

This paper, for the first time, reports integrated conceptual MBCT/biorefinery systems for unlocking the value of organics in municipal solid waste (MSW) through the production of levulinic acid (LA by 5wt%) that increases the economic margin by 110-150%. After mechanical separation recovering recyclables, metals (iron, aluminium, copper) and refuse derived fuel (RDF), lignocelluloses from remaining MSW are extracted by supercritical-water for chemical valorisation, comprising hydrolysis in 2wt% dilute H2SO4 catalyst producing LA, furfural, formic acid (FA), via C5/C6 sugar extraction, in plug flow (210-230°C, 25bar, 12s) and continuous stirred tank (195-215°C, 14bar, 20min) reactors; char separation and LA extraction/purification by methyl isobutyl ketone solvent; acid/solvent and by-product recovery. The by-product and pulping effluents are anaerobically digested into biogas and fertiliser. Produced biogas (6.4MWh/t), RDF (5.4MWh/t), char (4.5MWh/t) are combusted, heat recovered into steam generation in boiler (efficiency: 80%); on-site heat/steam demand is met; balance of steam is expanded into electricity in steam turbines (efficiency: 35%).

Selective and recyclable depolymerization of cellulose to levulinic acid catalyzed by acidic ionic liquid.

Cellulose depolymerization to levulinic acid (LA) was catalyzed by acidic ionic liquids (ILs) selectively and recyclably under hydrothermal conditions. The effects of reaction temperature, time, water amount and cellulose intake were investigated. Dilution effect becomes more pronounced at lower cellulose intake, dramatically improving the yield of LA to 86.1%. A kinetic model has been developed based on experimental data, whereby a good fit was obtained and kinetic parameters were derived. The relationships between IL structure, polymeric structure and depolymerization efficiency were established, shedding light on the in-depth catalytic mechanism of IL, inclusive of acidity and hydrogen bonding ability. The LA product can be readily separated through extraction by methyl isobutyl ketone (MIBK) and IL can be reused over five cycles without loss of activity. This environmentally friendly methodology can be applied to selective production of LA from versatile biomass feedstocks, including cellulose and derivatives, glucose, fructose and HMF.

One-pot synthesis of levulinic acid from cellulose in ionic liquids.

A simple and effective route for the production of levulinic acid (LA) from cellulose has been developed in SO3H-functionalized ionic liquids. The effects of ionic liquid structures, reaction conditions and combination of metal chlorides with ILs on the yield of LA were investigated, where the highest yield of 39.4% was obtained for 120 min in the presence of 1-(4-sulfonic acid) butyl-3-methylimidazolium hydrogen sulphate ([BSMim]HSO4) with addition of H2O. The catalytic activities of ionic liquids depended on the anions and decreased in the order: CF3SO3(-)>HSO4(-) > OAc(-), which was in good agreement with their acidity order. The ILs play a dual solvent-acid role for the cellulose conversion into LA and exhibited favorable catalytic activity over four repeated runs.

Formation of degradation compounds from lignocellulosic biomass in the biorefinery: sugar reaction mechanisms.

The degradation compounds formed during pretreatment when lignocellulosic biomass is processed to ethanol or other biorefinery products include furans, phenolics, organic acids, as well as mono- and oligomeric pentoses and hexoses. Depending on the reaction conditions glucose can be converted to 5-(hydroxymethyl)-2-furaldehyde (HMF) and/or levulinic acid, formic acid and different phenolics at elevated temperatures. Correspondingly, xylose can follow different reaction mechanisms resulting in the formation of furan-2-carbaldehyde (furfural) and/or various C-1 and C-4 compounds. At least four routes for the formation of HMF from glucose and three routes for furfural formation from xylose are possible. In addition, new findings show that biomass monosaccharides themselves can react further to form pseudo-lignin and humins as well as a wide array of other compounds when exposed to high temperatures. Hence, several aldehydes and ketones and many different organic acids and aromatic compounds may be generated during hydrothermal treatment of lignocellulosic biomass. The reaction mechanisms are of interest because the very same compounds that are possible inhibitors for biomass processing enzymes and microorganisms may be valuable biobased chemicals. Hence a new potential for industrial scale synthesis of chemicals has emerged. A better understanding of the reaction mechanisms and the impact of the reaction conditions on the product formation is thus a prerequisite for designing better biomass processing strategies and forms an important basis for the development of new biorefinery products from lignocellulosic biomass as well.

Conformal sulfated zirconia monolayer catalysts for the one-pot synthesis of ethyl levulinate from glucose.

Here we describe a simple route to creating conformal sulphated zirconia monolayers throughout an SBA-15 architecture that confers efficient acid-catalysed one-pot conversion of glucose to ethyl levulinate.