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Levulinic Acid - History, Properties, Global Market, Direct Uses, Safety

1.1 History and Properties

The first evidence for the formation of levulinic acid was obtained from the treatment of sugars with dilute acid solutions. The Italian-French Pharmacist Faustino Jovita Malaguti (Figure 1.1) reported, in 1835 [1], the treatment of sucrose with boiling diluted acid solutions, being able to identify formic acid and other ammonia-soluble compounds. In 1840, the Dutch chemist Gerardus Johannes Mulder reported the treatment of fructose with hydrochloric acid and was able to isolate acidic compounds [2]. Although these two scientists did not explicitly identify levulinic acid among the products, they were the first to conduct experiments in which levulinic acid would be formed. Nevertheless, the first identification of levulinic acid from the acid treatment of sugars was reported by Tollens in 1875 [3].

Levulinic acid (LA) is a keto-carboxylic acid bearing carbonyl and carboxyl groups in its structure (Figure 1.2). Therefore, the double functionalization makes it an interesting chemical for multiple purposes. Reactions involving levulinic acid are known since the 1870s, but the development of commercial processes and uses were not significant until the 1940s, mostly because of the high costs of the raw materials at the time, high capital costs, and low yields. With the use of cellulose-based feedstocks [4], the production of levulinic acid became more attractive motivating its general use.

Levulinic acid is the 4-oxo-pentanoic acid according to the International Union of Pure and Applied Chemistry (IUPAC) nomenclature. It may also be regarded as the 4-oxo-valeric acid. In the pure form, it is a solid that melts at 30-33?°C and boils at 245-246?°C at atmospheric pressure. Table 1.1 shows some selected properties of levulinic acid.

The first commercial production of levulinic acid dates from the 1940s when the A.E. Staley Manufacturing Company started a bath production using starch as raw material. The process [5] involves the initial mixing of proper amounts of starch and diluted hydrochloric acid at 100?°C in a preheater system. Then, the reaction mixture was autoclaved at 175-215?°C for a determined period. The effluent was neutralized with soda ash and the humins, which are insoluble by-products, were separated by filtration, whereas water and formic acid, formed as a by-product, were evaporated from the solution and the sodium chloride by centrifugation. Levulinic acid was obtained, like a light-colored liquid, upon vacuum steam distillation (Figure 1.3).

Figure 1.1 Faustino Jovita Malaguti (1802-1878) (https://www.redalyc.org/jatsRepo/1816/181662291006/html/index.html).

Source: CITMATEL.

Figure 1.2 Structure of levulinic acid.

Starch is a biopolymer made of hexoses, mainly glucose, that may be obtained from wheat, potato, and oat among numerous other crops. The chemical pathway from C6 sugars to levulinic acid is depicted in Scheme 1.1. The acid medium dehydrates the carbohydrates to intermediate compounds, like hydroxymethyl furfural (HMF), which can then be converted into levulinic acid also releasing a molecule of formic acid in the process.

Table 1.1 Selected properties of levulinic acid.

In the 1950s, the Quaker Oats Company developed a process to produce levulinic acid based on furfuryl alcohol as raw material. The company started producing furfural from sugarcane bagasse or corn cobs in 1922 [6, 7], upon heating the biomass in an aqueous solution of sulfuric or phosphoric acid. Furfural is an aromatic aldehyde mostly used in the production of resins at that time. In 1934, the company began the production of furfuryl alcohol from the high-pressure hydrogenation of furfural in Memphis, Tennessee, United States [8]. Then, a continuous process was developed, achieving 99% conversion of furfural in furfuryl alcohol with the use of copper-supported catalysts [9]. The production of levulinic acid from furfuryl alcohol began in 1957 and ended in 1972. The process involved the heating of furfuryl alcohol in the presence of aqueous hydrochloric acid, but small alcohol, such as methanol and ethanol, could also be employed affording the respective levulinate esters [10]. In the beginning, the company did not have enough uses for the levulinic acid produced. In 1959, Quaker Oats released [11] a contest for someone to bring a big idea on a commercial use of levulinic acid (Figure 1.4).

The overall chemical pathway to produce levulinic acid from C5 sugars is shown in Scheme 1.2. The pentoses are initially dehydrated to furfural in the acidic medium, usually hydrochloric acid. Then, in a second process, furfural is hydrogenated to furfuryl alcohol, which is further converted to levulinic acid upon acid-catalyzed hydrolysis.

Figure 1.3 Flow diagram of levulinic acid production process.

Scheme 1.1 Schematic reaction pathway for the production of levulinic acid from hexoses.

A biotechnological route to levulinic acid involving multiple steps has also been suggested [12]. It involves the fermentation of sugars, like glucose and fructose, to pyruvic acid as the first step (Scheme 1.3). The next steps may also involve biocatalysts. For instance, acetaldehyde can be produced from pyruvic acid with the use of pyruvate decarboxylase. In the same way, aldolases may be employed in the aldol condensation step. Dehydration of the 2-hydroxy-4-oxo-pentanoic acid, followed by the selective hydrogenation of the intermediate to levulinic acid, may be carried out either through biocatalysis or homogeneous/heterogeneous catalysis. Although technically feasible, this route has not been employed industrially, probably because of the numerous steps, which may require specific reaction conditions and separation procedures, significantly increasing the production costs.

Figure 1.4 Advertisement of the contest for uses of levulinic acid in 1959.

Source: Reproduced with the permission of the American Chemical Society.

Scheme 1.2 Schematic reaction pathway for the production of levulinic acid from pentoses.

Scheme 1.3 Biotechnological route for the synthesis of levulinic acid.

A fossil-based route to levulinic acid has also been developed [13]. The raw material is maleic acid, which is normally obtained from oxidation of benzene [14] or butenes [15]. However, recent developments point out possible routes from renewable feedstocks [16]. Scheme 1.4 shows the steps, which involve the decarboxylation of acetyl succinate.

The DSM company in Linz, Austria, has developed a small-scale process to produce 3?tons per day of levulinic acid from maleic acid, with an overall yield of about 80%. Nevertheless, the company has moved the production of levulinic acid from bio-based raw materials, discontinuing the fossil-based route.

Levulinic acid is a bifunctional molecule, having a keto-carbonyl and a carboxylic acid group. Therefore, it is expected to present the chemical properties of ketones and carboxylic acids. Scheme 1.5 shows the most common transformations of the levulinic acid molecule.

The levulinate esters find applications as fuel additives [17], as well as fragrancies. Inorganic levulinate salts are also important specialty chemicals; sodium levulinate is used in the cosmetic and food industry as preservative [18], whereas calcium levulinate is used in pharmaceutics and as a supplementary source of calcium. Hydrogenation may lead to different products. The ?-valerolactone (GVL) is normally produced upon the hydrogenation of...