Levulinic acid, derivatives

Scheme 9.3.4 Levulinic acid derivatives of industrial potential ...

Zhang J, Wu S, Li B, Zhang H (2012) Advances in the catalytic production of valuable levulinic acid derivatives. ChemCatChem 4 1230-1237... 

The reaction of the siloxycyclopropane with titanium(IV) chloride produces the titanium homoenolate (3-titaniopropionate) in good yield this, however, is relatively unreactive (eq 2). Addition of one equivalent of Ti(OR )4 generates a more reactive RTiChOR species, which smoothly reacts with carbonyl compounds below room temperature. The y-hydroxy ester adducts are useful synthetic intermediates and serve as precursors to y-lactones and cyclopropanecarboxylates. A useful variation involves the use of the cyclopropanecarboxylate ester as a functionalized homoenolate precursor to obtain levulinic acid derivatives (eq 3). ... 

Marketing Plan for Levulinic acid Derivatives, Antares Group Inc., Landover, MD, November 16 , 2000... 

In the acid hydrolysis process (79—81), wood is treated with concentrated or dilute acid solution to produce a lignin-rich residue and a Hquor containing sugars, organic acids, furfural, and other chemicals. The process is adaptable to all species and all forms of wood waste. The Hquor can be concentrated to a molasses for animal feed (82), used as a substrate for fermentation to ethanol or yeast (82), or dehydrated to furfural and levulinic acid (83—86). Attempts have been made to obtain marketable products from the lignin residue (87) rather than using it as a fuel, but currently only carbohydrate-derived products appear practical. 

HMF is an important versatile sugar derivative and is a key intermediate between bio-based carbohydrate chemistry and petroleum based industrial organic chemistry (1, 2). The most coimnon feedstock for HMF is fructose and reactions are carried out in water-based solvent systems using acid catalysis (3,4). HMF is unstable in water at low pH and breaks down to form levulinic acid and formic acid, resulting in an expensive HMF recovery process. In strongly polar organic co-solvents, such as dimethylsulfoxide (DMSO), levuhnic acid formation is reduced and HMF yields are improved (5). 

Another method for preparing pyrrole rings is by Ugi-type three-component condensation (Scheme 6.184). In the protocol published by Tye and Whittaker [345], levulinic acid was reacted with two different isonitriles and four amine building blocks (1.5 equivalents) to provide a set of eight pyrrole derivatives. While the previously published protocol at room temperature required a reaction time of up to 48 h and provided only moderate product yields, the microwave method (100 °C, 30 min) optimized by a Design of Experiments (DoE) approach (see Section 5.3.4), led to high yields of the desired lactams for most of the examples studied. 

In some cases, the hydrolysis reaction liberates the sugars from the biomass and converts them directly into derivatives such as furfural, hydroxymethyl furfural and/or levulinic acid. These derivatives can be further converted into various chemical intermediates. We will not discuss these further conversions as they are extensively reported in the literature, e.g., for furfural [15, 44], hydroxymethyl furfural [15, 44, 50] and levulinic acid [15, 44-47]. 

Levulinic acid is fairly easily converted into thiazole derivatives by the intermediate formation of an a-halogenated ketone such as the /3-bromo derivative (XL) or /3-chloro derivative, which reacts with thiourea to form 2-amino-4-methyl-5-thiazoleacetic acid (XLI) or with thioformamide to give 4-methyl-5-thiazoleacetic acid (XLII). The aminothiazole (XLI) and its ethyl ester (XLIII) have been converted into their corresponding sulfanilamide derivatives, (XLIV) and (XLV). These sulfanilamides, particularly the acid XLIV, have considerable chemotherapeutic activity moreover the acid possesses distinct solubility advantages over sulfathiazole itself. 

Another series of compounds which are easily accessible from levulinic acid are pyridazone and pyridazine derivatives. Levulinic acid and its esters condense almost quantitatively with hydrazine to ve 6-methyl-3-P3rridazinone (XLVI), which is readily dehydrogenated by means of bromine to give 6-methyl-3-pyridazone (XLVII). 

Chiral 4,4-dialkyl-l-cyclopentenones.1 The chiral bicyclic lactam 2, derived from levulinic acid and 1, on monoalkylation exhibits slight if any selectivity regardless of the electrophile. However, a second alkylation exhibits high endo-selectivity. This product (3), after reductive cleavage, furnishes a keto aldehyde that is cyclized by base to a chiral 4,4-disubstituted-2-cyclopentenone (4). Either antipode of 4 can be prepared by the sequence of alkylation. 

Levulinic acid is formed by the treatment of six-carbon sugar carbohydrates from starch or lignocellulosics with acids, or by add treatment plus a reductive step of five-carbon sugars derived from hemicellulose. Levulinic add can serve as a building block for the synthesis of many derivatives of interest may be the selective oxidation to succinic and acrylic add. [i-Acetylacrylic add could be used in the production of new acrylate polymers. 

N-Lemlinylnucleosides. N-Levulinylcytidine (1) can be prepared by reaction of the free nucleoside with levulinic anhydride in refluxing methanol (70% yield), but higher yields (86%) are obtained by reaction of the trisilyl derivative with levulinic acid. I)( (, and DMAP, followed by desilylation (F ). N-Lcvulination of trisilylad-enosinc is best effected with levulinic acid and N-ethoxycarbonyl-2-ethoxy-l,2-... 

When the structure of biomass components has to be quite drastically rearranged compared to the building blocks needed, synthesis gas or different sugars can serve as platform chemicals. The latter can be converted, for example, to sugar-derived building blocks (Figure 2.2.3) - that is, to glycerol, sorbitol, levulinic acid, and furfural. 

The liquid portion of biomass-derived process samples may also contain carbohydrate degradation products, such as 5-(hydroxymethyl)-2-furaldehyde (HMF), levulinic acid, and furfural, as well as other components of interest, such as organic acids and sugar alcohols. Portfolio methods are available for the quantitative measurement of these degradation products and byproducts of polymer hydrolysis. 

Dahlmann, J., Hydrolytic method for the production of levulinic acid and its derivatives from biomass and sugars. Chemische Berichte 1968, 101, 4251—4253. 

This mechanism implies that a portion of the charred residue from the pyrolysis of cellulose could be derived from the secondary reactions involved in the decomposition of levoglucosan. In the production of levulinic acid, about 25 % of the initial D-glucose residues is converted into the humin that separates as an insoluble, charred residue. This humin could be formed from 5-(hydroxymethyl)-2-furaldehyde, which is readily polymerized and decomposed on heating under acid conditions. The kinetic investigations indicate that the humin could also be formed from the reaction of 5-(hydroxy-methyl)-2-furaldehyde with one of its precursors. ... 

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