Levulinic acid,.

On redistillation under reduced pressure a fraction boiling over a range of not more than 2° (e.g., i37-i39°/io mm.) is obtained with very little loss this fraction solidifies almost completely at 30°. The yield is 72-76 g. (22-23 per cent of the theoretical amount). 

Equally good results may be obtained with starch the mixture, however, must be warmed more slowly as it is apt to foam at the outset. 

When larger quantities of levulinic acid are to be prepared it has been found by the checkers to be more convenient to fractionally distil the first filtrate under reduced pressure, without evaporating to dryness and extracting with ether. In this case a considerable quantity of tarry residue remains in the distilling flask. The yields are equally good. 

The only practical methods for preparing levulinic acid depend upon the action of mineral acids upon carbohydrates, a reaction discovered by Grote and Tollens,1 who heated cane sugar with dilute sulfuric acid. The method above described is essentially that of Conrad,2 descriptions of which frequently have appeared 3 in the subsequent literature. The use of vacuum distillation was suggested by Kent and Tollens.4 Levulinic acid has also been prepared from starch by the action of hydrochloric acid.5 

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Under acidic conditions, furfuryl alcohol polymerizes to black polymers, which eventually become crosslinked and insoluble in the reaction medium. The reaction can be very violent and extreme care must be taken when furfuryl alcohol is mixed with any strong Lewis acid or Brn nstad acid. Copolymer resins are formed with phenoHc compounds, formaldehyde and/or other aldehydes. In dilute aqueous acid, the predominant reaction is a ring opening hydrolysis to form levulinic acid [123-76-2] (52). In acidic alcohoHc media, levulinic esters are formed. The mechanism for this unusual reaction in which the hydroxymethyl group of furfuryl alcohol is converted to the terminal methyl group of levulinic acid has recendy been elucidated (53). 

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. 

When levulinic acid (CH3CCH2CH2CO2H) was hydrogenated at high pressure over a nickel catalyst at 220°C, a single product, C5Hg02, was isolated in 94% yield. This compound lacks hydroxyl absorption in its IR spectrum and does not immediately liberate carbon dioxide on being shaken with sodium bicarbonate. What is a reasonable structure for the compound ... 

Syntheses of heterocycles on the basis of levulinic acid 99UK80. 

Lavulin, n. levulin. -saure, /. levulinic acid. Lavulkan, n. a kind of synthetic rubber. T. N. Lavulose,/. levulose, n-fructose. 

Lactic acid and levulinic acid are two key intermediates prepared from carbohydrates [7]. Lipinsky [7] compared the properties of the lactide copolymers [130] obtained from lactic acid with those of polystyrene and polyvinyl chloride (see Scheme 4 and Table 5) and showed that the lactide polymer can effectively replace the synthetics if the cost of production of lactic acid is made viable. Poly(lactic acid) and poly(l-lactide) have been shown to be good candidates for biodegradeable biomaterials. Tsuji [131] and Kaspercejk [132] have recently reported studies concerning their microstructure and morphology. 

The carboxyl terminated ACPA, 4,4 -azobis-(4-cya-nopentanoic acid), turned out to be a suitable reagent in condensation reactions. This compound can be prepared by Strecker s synthesis from levulinic acid following the method of Haines and Waters [12]. Regarding the formation of polymeric azo initiators, Matsakuwa et al. [13] reported on the condensation of ACPA with various diols and diamines in the presence of a condensation agent, I-methyl-2-chlorpyridinium iodide, and a cata-... 

Scheme 11 Microwave-assisted Ugi reaction of levulinic acid 30...

Linking the ketone and carboxylic acid components together in an Ugi reaction facilitates the synthesis of pyrrolidinones amenable to library design. The three-component condensation of levulinic acid 30, an amine and isocyanide proceeds under microwave irradiation to give lactams 31 [65]. The optimum conditions were established by a design of experiments approach, varying the equivalents of amine, concentration, imine pre-formation time, microwave reaction time and reaction temperature, yielding lactams 31 at 100 °C in poor to excellent yield, after only 30 min compared to 48 h under ambient conditions (Scheme 11). 

The photo-Kolbe reaction is the decarboxylation of carboxylic acids at tow voltage under irradiation at semiconductor anodes (TiO ), that are partially doped with metals, e.g. platinum [343, 344]. On semiconductor powders the dominant product is a hydrocarbon by substitution of the carboxylate group for hydrogen (Eq. 41), whereas on an n-TiOj single crystal in the oxidation of acetic acid the formation of ethane besides methane could be observed [345, 346]. Dependent on the kind of semiconductor, the adsorbed metal, and the pH of the solution the extent of alkyl coupling versus reduction to the hydrocarbon can be controlled to some extent [346]. The intermediacy of alkyl radicals has been demonstrated by ESR-spectroscopy [347], that of the alkyl anion by deuterium incorporation [344]. With vicinal diacids the mono- or bisdecarboxylation can be controlled by the light flux [348]. Adipic acid yielded butane [349] with levulinic acid the products of decarboxylation, methyl ethyl-... 

C47H7,NOis 55881-06-6) see Midecamycin acetate Ieuco-l,4,S,8-tetrahydroxyanthraquinone (C 4HsOfi 81-60-7) see Mitoxantrone levonorgestrel acetate (C2,H i07 13732-69-9) see Norgestimate levulinic acid... 

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). 

This cyclocondensation reaction has also been examined with substituted levulinic acids ... 

A pyridazine has found use as an antihypertensive agent. When levulinic acid is reacted with hydrazine, 153 results. This is aromatized to pyridazine 154 when reacted with bromine in acetic acid. One presumes a spontaneous dehydrobromination... 

Urine ( -aminolevuli nic acid) Dilution of sample reaction with ethylacetoacetate and ethylacetate to form -amino-levulinic acid-pyrrole reaction with Erhlich s reagent Spectrophotometry No data No data Tomokuni and Ichiba 1988... 

Beside the use of a single enzyme, a cocktail of different biocatalysts can also be used in performing a domino process, provided that the enzymes do not interfere one with another. This approach was used by Scott and coworkers in the synthesis of precorrin-5 (8-61) (Scheme 8.16) [24]. Starting from 6-amino levulinic acid (ALA) 8-60, a mixture of eight different enzymes including the ALA-dehydratase to form porphobilinogen (PBG), as well as PBG deaminase and co-synthetase to furnish the tetracyclic uroporphyrinogen III (8-62) as intermediates, was employed to provide precorrin-5 (8-61) in 30% yield. 

Biacetyl monoxime has been prepared by the action of amyl nitrite on methyl ethyl ketone using sodium hydroxide1 or hydrochloric acid 2 as a condensing agent, and by melting nitroso-levulinic acid.3... 

A rapid synthesis of carbon-14 labeled [l-14C]levulinic acid from simple building blocks has been demonstrated by Johansen and coworkers (Scheme 6.172) [324], In all three of the synthetic steps, starting from bromo[l-14C]acetic acid, microwave heating was used to accelerate the reactions, allowing a total preparation time of less than 1 h. The labeled levulinic acid was subsequently transformed into (5Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone in a bromination/oxidation sequence (not shown), a potent quorum sensing inhibitor. 

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. 

With regard to the formation of levulinic acid by acid treatment of 5-(hydroxymethyl)-2-furaldehyde, Pummerer, Guyot and Birkofer92 pro-... 

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