Levulinic acid preparation

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-... 

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. 

Levulinic acid is obtained by hydrolysis of cellulose-containing biomass. R D is actively conducted at DuPont Co. to employ levulinic acid for the synthesis of pyr-rolidones (solvents and surfactants), a-methylene-y-valerolactone [monomer for the preparation of polymers similar to poly(methyl methacrylate)], and levulinic acid esters (fuel additives) [26]. 

A variety of cyclic products have been prepared from educts containing carbonyl as well as carboxylic groups. Thus, Hanusch-Kompa and Ugi prepared a large number of five-membered cyclic gamma-lactam compounds like 44 from levulinic acid. Other carbonylic acids can lead to compounds like 45, which is made from phthalaldehyde acid, valine methylester, and tert-butylisocyanide. The products like 46 and 47 can result from the U-4CR and further cyclization. 

Hydrobromic acid, although it shows marked advantages over other acids in the preparation of levulinic acid, is obviously too expensive for the manufacture of this material. Some improvement in the yield obtained with hydrochloric acid is effected, however, by adding a small amount of sodium bromide to the mixture. ... 

There are few good synthetic methods for these compounds because they are unstable, and must be preserved at low temperatures (Section 3.14.3.6). 2-Hydroxythiophene was first prepared by oxidation of the Grignard reagent, and later from 2-thienyllithium. The compound was also obtained by acid-catalyzed dealkylation of 2-r-butoxythiophene (equation 60). 3-Hydroxythiophene was also obtained by oxidation of 3-thienyllithium (63AHC(1)1>. 5-Methyl-2-hydroxythiophene was obtained in low yield by the Paal synthesis from levulinic acid (equation 61 Section 3.15.3.1.3). 3,5-Dinitro-2-chlorothiophene was converted to 3,5-dinitro-2-hydroxythiophene by hydrolysis with sodium formate in anhydrous methanol (equation 62). 

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. 

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-... 

The breakdown of furan aldehydes leads to the formation of formic and levulinic acid. Moreover, acetic acid is formed during the degradation of hemicellulose. Partial breakdown of lignin can generate a variety of phenolic compounds (23), which also inhibit S. cerevisiae (14,15). In contrast to furan aldehydes and aliphatic acids, the toxic effect of specific phenolic compounds is highly variable (15). Different raw materials and different approaches to prepare lignocellulose hydrolysates will result in different concentrations of the fermentation inhibitors (16,17). 

Hydroxymethylfurfural is not volatile by steam. It is prepared from hexoses in the presence of an acid catalyst by short heat treatment to avoid further degradation to levulinic acid. After recovery by solvent extraction hydroxymethylfurfural is purified by distillation. Levulinic acid can be prepared in good yield from hexose-based polysaccharides by heating with acids. In this reaction formic acid is liberated and levulinic acid is easily lactonized to form a- and /3-angelica lactones (Fig. 2-31). 

Levulinic Acid. Dehydration of glucose or other monomeric and polymeric C6 sugars leads to the direct formation of levulinic acid (LA) as a potential primary building block for the biorefinery, and several reviews have described its potential commercial utility 477,478 The preparation of levulinic acid is not difficult, although the mechanism of its formation from carbohydrates is complex, and offers several alternative decomposition pathways (equation 3).479... 

Dimethyl-2-pyrrolidone has been prepared by the reaction of 5-methyl-2-pyrrolidone with excess methyl iodide4 and by the catalytic hydrogenation of a mixture of levulinic acid and methylamine.6... 

Diphenolic acid, the condensation product of levulinic acid and phenol, is useful in the preparation of modified phenol-formaldehyde resins, polyether resins, or as monocarboxylic acid chain stoppers in alkyd resins (152). It can be substituted for bisphenol-A, the primary raw material in the production of epoxy resins (153). 

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 add. ... 

Addition of the anion of 2-methyl-l,3-cyclopentadione (348) to protoane-monin (349), easily prepared from levulinic acid in four steps (207), led to adduct 350 in low yield due to ready self-condensation (Scheme 39). Transesterification with acidic methanol set the alcohol free, which cyclized spontaneously to the 1 1 mixture of ketals 351 and 352. To enhance the yield of the ketal 352, ketal 351 was recycled by equilibration in acidic methanol. Under Kharash-Grignard conditions, the isopropenyl group added unselectively in 1,4-mode and the ester enolate 353... 

Many of the methods listed for the preparation of hydroxy acids (Table 47) have been used to prepare lactones directly. Reduction of levulinic acid, CHjCOCHjCHjCOjH, by sodium and alcohol or by catalytic hydrogenation over Raney nickel leads to "y-valerolactone. S-Captolactone is prepared in a similar manner from y-acetobutytic acid. Other S-lactones have been formed by catalytic hydrogenation of the corresponding aldehydo... 

Physical Data bp 76-80 °C/0.05 mmHg [a]o 95.5°. Preparative Methods the richly functionalized chiral hicyclic lactam is easily procured by condensation of commercially available (S)-valinol and levulinic acid in 86% yield (eq 1) Similar hicyclic lactams have been prepared from other amino alcohols. These hicyclic lactams have served as precursors to a variety of enantiomerically pure compounds that possess quaternary stereocenters. An extensive review on the utility of chiral, nonracemic hicyclic lactams is available. ... 

The levulinoyl esters are prepared from the free hydroxyl group by treatment of levulinic acid with DCC [255,256] or l-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) [257] in the presence of DMAP (O Scheme 38). Additionally, 3 - and 5 -0-levulinyl protected derivatives of 2 -deoxy nucleosides have been prepared by regioselective enzymatic acylation using a variety of lipases and acetonoxime levulinate as acylating agent [258]. In contrast to other ester substituents, the 0-levulinoyl group is far less prone to migration [259]. 

Preparation. Tollens discovered that levulinic acid can be obtained by the action of dilute mineral acids on carbohydrates starting materials include sucrose, starch, glucose, furfural," and 4-hydroxymethylfurfural." In the Organic Syntheses procedure a solution of 500 g. of sucrose in 1 1. of water is treated with 250 ml. of... 

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