Resources, Conservation and Recycling 28 (2000) 227–239

www.elsevier.com/locate/resconrec

Production of levulinic acid and use as a

platform chemical for derived products
Joseph J. Bozell a,*, L. Moens a, D.C. Elliott b, Y. Wang b,
G.G. Neuenscwander b, S.W. Fitzpatrick c, R.J. Bilski d,
J.L. Jarnefeld e
a
National Renewable Energy Laboratory, 1617 Cole Boule6ard, Golden, CO 80401, USA
b
Pacific Northwest National Laboratory, P.O. Box 999, MSIN K2 -12, Richland, WA 99352, USA
c
Biofine, 245 Winter Street, Waltham, MA 02154, USA
d
Chemical Industry Ser6ices Inc., 2707 Stemwell Boule6ard, Richmond, VA 23236, USA
e
New York State Energy Research and De6elopment Authority, Corporate Plaza West,
286 Washington A6enue Extension, Albany, NY 12203, USA

Abstract

Levulinic acid (LA) can be produced cost effectively and in high yield from renewable
feedstocks in a new industrial process. The technology is being demonstrated on a 1 ton/day
scale at a facility in South Glens Falls, New York. Low cost LA can be used as a platform
chemical for the production of a wide range of value-added products. This research has
demonstrated that LA can be converted to methyltetrahydrofuran (MTHF), a solvent and
fuel extender. MTHF is produced in \80% molar yield via a single stage catalytic
hydrogenation process. A new preparation of d-aminolevulinic acid (DALA), a broad
spectrum herbicide, from LA has also been developed. Each step in this new process
proceeds in high ( \80%) yield and affords DALA (as the hydrochloride salt) in \ 90%
purity, giving a process that could be commercially viable. LA is also being investigated as
a starting material for the production of diphenolic acid (DPA), a direct replacement for
bisphenol A. © 2000 ACEEE Published by Elsevier Science B.V. All rights reserved.

Keywords: Levulinic acid; Methyltetrahydrofuran; d-Aminolevulinic acid; Diphenolic acid; Paper sludge;
Renewables to chemicals; Platform chemicals

* Corresponding author. Tel.: +1-303-3846276; fax: +1-303-3846103.

E-mail address: [email protected] (J.J. Bozell)

0921-3449/00/$ - see front matter © 2000 ACEEE Published by Elsevier Science B.V. All rights reserved.
PII: S 0 9 2 1 - 3 4 4 9 ( 9 9 ) 0 0 0 4 7 - 6
228 J.J. Bozell et al. / Resources, Conser6ation and Recycling 28 (2000) 227–239

1. Introduction

Biomass can be used as a raw material to produce large numbers of chemicals,

each with the potential to be as fundamental to the chemical industry as methane
or BTX. Yet, to date, many of these products have failed in the marketplace
because they do not pass the most practical test of market viability: is the product
available at a low enough cost to use as a chemical product or intermediate?
Levulinic acid (1, LA, 4-oxopentanoic acid), has frequently been proposed as such
a building block [1,2].

Despite its status as an expensive and relatively small market specialty chemical
(about 1 million lb/year at $4.00 –$6.00/lb), LA and its derivatives have found use
in highly diverse areas. Some of these applications are summarized in Table 1.1
The preparation of LA is not difficult, and a number of approaches have been
reported for its synthesis. The most widely used approach is the dehydrative
treatment of biomass or carbohydrates with acid [20–23]. LA has also been
produced by hydrolysis of acetyl succinate esters [24], by acid hydrolysis of furfuryl
Table 1
Selected levulinic acid applications

Application Reference

Chiral reagents [3]

Biologically active materials [4]
Polyhydroxyalkanoates [5]
Polymers [6,7]
Polymerization initiators [8]
Antifouling compounds [9]
Personal care products [10]
Lubricants [11]
Adsorbents [12]
Printing/inks [13]
Coatings [14]
Electronics [15]
Photography [16]
Batteries [17]
Drug delivery [18]
Corrosion inhibitors [19]

1
The applications cited in Table 1 and subsequent tables are illustrative but not exhaustive. Many
additional examples exist in the patent and open literature. In each case, LA or its derivatives are listed
as useable in the given application, but may not be the primary focus of the citation.
 J.J. Bozell et al. / Resources, Conser6ation and Recycling 28 (2000) 227– 239 229

Fig. 1. The Biofine process.

alcohol [25], by oxidation of ketones with ozone [26] or with Mn(OAc)3 [27]. LA has
been produced by Pd-catalyzed carbonylation of ketones [28] and by alkylation of
nitroalkanes [29]. However, these methods frequently form large amounts of side
products and intractable materials, or require expensive starting feedstocks.
Recently, a new process developed by Biofine Corporation eliminated many of the
existing problems with LA production. The Biofine process uses acid hydrolysis of
6-carbon sugars as the key step for LA production, and minimizes side product
formation and the resulting separation problems by significantly improving the
traditional engineering of the LA production process through a novel, two reactor
system (Fig. 1). [30,31].
The process supplies carbohydrate containing materials to a first reactor where
they are hydrolyzed at 210 – 230°C for 13–25 s in the presence of 1–5% mineral acid.
This initial hydrolysis produces hydroxymethylfurfural, which is removed continu-
ously and supplied to a second reactor. In the second reactor, the hydroxymethylfur-
fural is hydrolyzed further at 195–215°C for 15–30 min to produce LA, which is
again continuously removed. The LA yield is ] 60%, based on the hexose content
of the carbohydrate-containing starting material, one of the highest reported in the
literature. The result is a cost effective production of LA, making it suitable as a
starting material for a wide variety of products. The technology can be successfully
employed using diverse cellulose-containing waste materials such as paper mill
sludge, urban waste paper, agricultural residues and cellulose fines from papermaking
as starting materials. Economic projections indicate that the LA production cost
could fall as low as $0.04 – $0.10/lb depending on the scale of the operation.
Furthermore, the impact on waste reduction and domestic energy use is large.
Department of Energy metrics project energy savings of 75.6 trillion Btu/year and
waste reduction of 26.2 million tons/year by 2020. Biofine is operating a 1 ton/day
pilot plant facility in South Glens Falls, New York to demonstrate the ability to
scalethis process to an industrially useful size.2

2
Projections are based on MTHF as a fuel oxygenate, addressing a potential market of 8 billion
lb/year.
230 J.J. Bozell et al. / Resources, Conser6ation and Recycling 28 (2000) 227–239

Table 2
Products from LA and potential LA markets demand

Product Use Potential LA market (million lb/year)

MTHF Fuel extender 10 000–100 000

DALA Biodegradable herbicide 175–350
Diphenolic acid Monomer 35
THF Solvent 200
BDO Monomers 200

Typically, however, a biomass derived material must pass a second test: what can
the material be used for and is there a market? To address this issue, a research
consortium was established in 1996. The consortium brought together two indus-
trial partners, Biofine and Chemical Industry Services, with the National Renew-
able Energy Laboratory (NREL), the Pacific Northwest National Laboratory
(PNNL), and the New York State Energy Research and Development Authority
(NYSERDA). This consortium has been developing technology to convert LA into
a larger suite of chemical products. Laboratory research has studied three products:
methyltetrahydrofuran (MTHF), a fuel additive with a huge potential market,
d-amino levulinic acid (DALA) a broad spectrum herbicide/pesticide with a pro-
jected market of 200 – 400 million pounds/year, and diphenolic acid (DPA), a
substitute for bisphenol A in polymer manufacture. These products have the
potential to expand the market need for LA into the hundreds of millions of
pounds. Table 2 summarizes possible market demand for LA from a group of LA
derivatives. In the past, LA has been investigated as a starting material for several
of these materials, however, its traditionally high cost has prevented widespread use
of known technology (MTHF: [32,33]; DALA: [34]; DPA: [35]). The combination
of a low cost source of LA with new technology has opened up new opportunities
for LA as a chemical feedstock.

2. Results — new approaches to derivatives of levulinic acid

2.1. Methyltetrahydrofuran

Large scale use of LA has recently been linked to automobile fuel extenders, such
as MTHF. It is miscible with gasoline at all proportions and has favorable
oxygenate and vapor pressure properties [1]. Since the U.S. uses about 100 billion
gallons of gasoline/year, replacement of as little as 1% (similar in volume to the
usage of ethanol in gasohol) would result in a yearly demand of 1 billion gallons of
MTHF, equivalent to over 10 billion pounds of LA. Early work in the 1980s [1,36]
investigated the use of two LA derivatives, MTHF and angelicalactone (AL), as
fuel blending agents. Direct conversion of LA to MTHF is reported to occur in
only low yield [37]. However, several indirect LA processing routes are reported
that lead to MTHF (Fig. 2).
 J.J. Bozell et al. / Resources, Conser6ation and Recycling 28 (2000) 227– 239 231

Fig. 2. Conversion of LA to MTHF.

An intermediate central to LA based MTHF processes is g-valerolactone (GVL).

This material can be prepared by several different routes. Simple heating of LA to
about 160°C in the presence of acid gives a high yield of AL [1,38]. A subsequent
reduction step converts AL to GVL, and then to 1,4-pentanediol (PDO). PDO is
readily dehydrated to MTHF upon heating in the presence of acid [39]. Alterna-
tively, LA can also be reduced to 4-hydroxypentanoic acid (HPA). This material
can undergo cyclization to GVL and conversion to MTHF, again via PDO.
The conversion of LA to GVL has been investigated by several groups. Schutte
and Thomas hydrogenated LA using a platinum oxide catalyst to give GVL in 87%
yield [40]. LA was hydrogenated to GVL in the neat liquid phase with a Raney
nickel catalyst in 94% yield [37,41]. Changing to a copper–chromite catalyst
produced a complex mixture of GVL, PDO and MTHF. This is the first report of
MTHF as a byproduct, although its ready formation from PDO by thermal
decomposition/dehydration explains its presence. Rhenium catalysts [Re black,
Re(IV) oxide hydrate] for hydrogenation of LA to GVL have also been described
[42]. The subsequent reduction of GVL to PDO has also been studied. Hydrogena-
tion of GVL over copper – chromite catalyst gave 79% PDO [43]. In a later study up
to 83% yield of PDO was achieved. At higher reaction temperatures, PDO yields
dropped and MTHF was found in a low-boiling fraction [37].
More recent studies have focused on homogeneous catalysis of the hydrogenation
steps. Both ruthenium and rhodium complexes catalyze hydrogenation of LA at
low temperature (60°C) in aqueous solutions [44,45]. GVL is also produced from
LA in 85 – 100% yield using ruthenium iodocarbonyl complexes [46]. Ruthenium
triphenylphosphine complexes give 99% conversion and 86% yield of GVL in
toluene solution [47].
The major projected use of MTHF is as a transportation fuel extender. Because
it is miscible with gasoline at all proportions and hydrophobic, MTHF could be
blended at the refinery and transported by pipeline. In contrast, ethanol must be
232 J.J. Bozell et al. / Resources, Conser6ation and Recycling 28 (2000) 227–239

added later in the distribution process because contamination with water can cause
phase separation. MTHF can be blended in gasoline up to 60% by volume without
adverse engine performance [48]. MTHF has a higher specific gravity than gasoline;
therefore, mileage from MTHF blended fuel would not decrease. As a component
of ‘P-series’ fuels (recently approved by the Department of Energy), MTHF can be
used to meet the requirements for alternative fuel fleet vehicles stipulated by the
Energy Policy Act of 1992. The ‘P-series’ fuels are blended such that they have a
minimum antiknock index of 87 and a maximum vapor pressure of 15 psi. P-series
fuel emissions are generally below those for reformulated gasoline using methylter-
tiarybutyl ether (MTBE) and are well below federal emissions standards.
Work carried out at PNNL has built upon the background chemical research in
LA reactions. Batch reactor tests were performed to screen a series of catalyst
formulations and processing conditions for use in hydrogenating levulinic acid.
Initial tests in dilute phase with 1,4-dioxane solvent have provided the basis of
continuous-flow reactor tests with the Biofine LA product from their demonstration
plant. Laboratory-scale work has shown the conversion of LA into MTHF with a
single-bed catalytic hydrogenation process that uses a catalyst consisting of palla-
dium and rhenium metals on carbon at elevated temperature and pressure. The LA
undergoes multiple hydrogenations (3 mol of hydrogen per mole of LA) and two
dehydrations in a single reaction step. PNNL was recently issued a patent for the
catalyst composition and the operating parameters [49]. Operating conditions are
240°C and 1500 psig using liquid hourly space velocities around 1 l of LA/l of catalyst
bed/h. Lab tests have indicated an 83% yield on a theoretical (molar) basis. On a
weight basis, the yield is 63 pounds of MTHF for every 100 pounds of LA. Literature
values using competing processes give low yields (3%) of MTHF as a minor
by-product. Efforts are under way to scaleup production of MTHF from LA in a
mobile processing unit at Biofine’s demonstration plant. MTHF production is
projected at about 20 gallons per day.

2.2. D-aminole6ulinic acid (DALA)

DALA (2) is a broad spectrum, biodegradable herbicide that shows high activity
toward dicotyledonous weeds while showing little activity toward monocotyledonous
crops such as corn, wheat, or barley. DALA is completely biodegradable with a
broad spectrum of activity rivaling and possibly exceeding that of Monsanto’s
Roundup®. DALA exerts its effects by stimulating overproduction of tetrapyrroles
in the plant at night. In daylight, the accumulated tetrapyrroles photosensitize the
formation of singlet oxygen in the plant, leading to its death [50,51]. More recently,
DALA has been found to be useful as an insecticide and as a component in
photodynamic therapy as a cancer treatment [52,53].
 J.J. Bozell et al. / Resources, Conser6ation and Recycling 28 (2000) 227– 239 233

A variety of synthetic routes for DALA have been reported. DALA can be
prepared from N-substituted amino acids [54], and through stepwise buildup of the
carbon chain [55]. More elegant strategies used cyclic starting materials such as
furfurylamine [56], 5-hydroxy-2-pyridone [57], N-methoxycarbonyl-3-piperidinones
[58], and 5-hydroxymethyl-2-furfural [59]. The biological activity of DALA has also
led to a search for processes that can be applied at commercial scales. A number of
DALA production patents have been issued [60–63].
The obvious starting material for the preparation of DALA is LA, which
requires formation of a C – N bond at the C5 carbon. Several amination methods
have been successful on laboratory scale, but none of them have been scaled up to
commercial levels. The most common approach for activating the C5 position
toward amination is bromination of LA in an alcohol medium to give mixtures of
5-bromo- and 3-bromoesters that are separated by distillation [64]. The 5-bro-
molevulinate is aminated using nucleophilic nitrogen species such as sodium azide
[65]. These various steps are combined to give the conventional DALA synthesis
shown in Fig. 3 [34]. LA (1) is brominated to give 5-bromolevulinic acid 3. To
introduce the key amino group, 3 is treated with potassium phthalimide, giving
intermediate 4. Acid hydrolysis of 4 gives DALA. The major difficulties with this
approach are the relatively low yields in the first two steps and the generation of a
large amount of a waste product, 5. Introduction of the amino group into DALA
is highly inefficient because only a single atom from the potassium phthalimide is
used. The remainder of the structure is waste. More generally, none of the reported
approaches are suitable for large scale manufacture of DALA because of the need
for multistep syntheses, expensive starting materials, or toxic intermediates.
The key areas of study at NREL for DALA manufacture have been the
improvement of each of these synthesis steps with particular focus on overall cost
effectiveness. The NREL work has significantly improved the yield of the first two
steps and the efficiency of the second (Fig. 4).

Fig. 3. Conventional synthesis of DALA.

234 J.J. Bozell et al. / Resources, Conser6ation and Recycling 28 (2000) 227–239

Fig. 4. NREL Synthesis of DALA.

The NREL synthesis also begins with LA, which is brominated in MeOH to give
methyl 5-bromolevulinate 6. This ester is treated with diformylamide anion 7 (easily
prepared from NaOMe and formamide) to give 8 [66]. Acid hydrolysis of this
intermediate leads to DALA. The only side product observed from the hydrolysis
is formic acid. Each of the steps proceeds in high ( \ 80%) yield and affords DALA
(as the hydrochloride salt) in \ 90% purity, giving a process that could be
commercially viable [67]. The material prepared by this process has been submitted
for herbicide testing at the University of Illinois. The first samples were 85% as
effective as a control sample of DALA. More recently, the process has been
improved further by use of a different amination reagent for the second step of the
process. This new reagent generates much less waste, and can be used in several
solvents.

2.3. Diphenolic acid

Diphenolic acid (9) is a material that has found wide application in the
production of polymers and other materials.

The material is easily prepared from the reaction of LA with two moles of phenol
[68]. DPA can serve in many of the same applications as bisphenol A (BPA), but
the lower cost of the latter has reduced the DPA market. Since the Biofine process
offers LA at a much lower cost, it is reasonable to again consider DPA as a
renewables based polymer precursor. Work sponsored by NYSERDA has started
at Rensselae Polytechnic Institute on near term applications for DPA, particularly
 J.J. Bozell et al. / Resources, Conser6ation and Recycling 28 (2000) 227– 239 235

ones that displace currently marketed BPA products. Researchers are exploring
DPA/BPA copolycarbonate and copolyarylate combinations that could partially or
wholly displace BPA formulations. Within these combinations, researchers are also
studying the use of dibrominated DPA in fire retardants. Brominated DPA also has
some promise as an environmentally acceptable marine coating that could replace
the toxic tributyltin. Further development of DPA uses will concentrate on highly
crosslinked polymers and charged polyesters, or ‘ionomers’.
Market penetration of Biofine’s DPA has near term potential; DPA has been
produced commercially for many years by reacting LA with phenol. LA’s price is
the most important component of DPA’s price, which is currently around $3/lb. If
LA were produced for $1/lb, DPA could likely be produced for $1.20/lb. The
market for BPA is estimated to be over 500 million lb/year. A $1.20/lb DPA might
not only capture 20% of this market, but also recapture some 5 million lb/year of
its old use as a coating material. DPA may even perform better in some applica-
tions. The goal is to achieve a DPA market size of 15 million lb/year over the next
5 years, creating a 7 million lb/year market for LA.
DPA’s widest use is as a component in polymers, however, it has also found
applications in several other area. Applications are summarized in Table 3.

3. Conclusions

The availability of inexpensive LA from the Biofine process will open up new
opportunities for the cost-effective production of chemicals from renewable feed

Table 3
Selected diphenolic acid applications

Application Reference

Thermoplastics [69]
Polysulfones [70]
Polyphenylene ethers [71]
Hyperbranched and dendrimeric polyesters [72]
Thermally reversible isocyanates [73]
Phenolic and polyester resins [74]
Polycarbonates [75]
Heat sensitive recording media [76]
Electronics [77]
Printing/inks [78]
Fragrances [79]
Medicinals [80]
Dyes/pigments [81]
Lubricants [82]
Fire retardant materials [83]
Polymeric coatings [84]
Adhesives [85]
Paints [86]
236 J.J. Bozell et al. / Resources, Conser6ation and Recycling 28 (2000) 227–239

stocks. More broadly, the work described in this paper is an early example of a
‘biomass refinery’, taking complex raw materials from renewable sources, and
converting them into a wider slate of discrete products. Further research will
undoubtedly reveal other examples of these types of technology.

Acknowledgements

This work was supported by the Office of Industrial Technologies, U.S. Depart-
ment of Energy.

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