Raney-Ni catalyzed conversion of levulinic acid to 5-methyl-2-pyrrolidone using ammonium formate as the H and N source

Article abstract of DOI:10.1016/j.tetlet.2018.03.087

Renewable biomass based levulinic acid was converted to 5-methyl-2-pyrrolidone in 94% yield by a Raney-Ni catalyzed process using ammonium formate in aqueous medium and heating at 180 °C for 3 h. The Raney-Ni could be reused for four catalytic cycles with about 10% loss in catalytic activity. In a similar reaction levulinic acid could be converted 1-substituted-5-methyl-2-pyrrolidones in 90–95% yield by using a mixture of formic acid and the corresponding primary amine.

Full text of DOI:10.1016/j.tetlet.2018.03.087

Accepted Manuscript
Raney-Ni catalyzed conversion of levulinic acid to 5-methyl-2-pyrrolidone us-
ing ammonium formate as the H and N source
Ananda S. Amarasekara, Yen Maroney Lawrence
PII:
S0040-4039(18)30424-6
https://doi.org/10.1016/j.tetlet.2018.03.087
TETL 49856
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
2 March 2018
27 March 2018
29 March 2018
Please cite this article as: Amarasekara, A.S., Lawrence, Y.M., Raney-Ni catalyzed conversion of levulinic acid to
5-methyl-2-pyrrolidone using ammonium formate as the H and N source, Tetrahedron Letters (2018), doi: https://
doi.org/10.1016/j.tetlet.2018.03.087
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1
Raney-Ni catalyzed conversion of levulinic acid to 5-methyl-2-
pyrrolidone using ammonium formate as the H and N source
Ananda S. Amarasekara*, Yen Maroney Lawrence
Department of Chemistry, Prairie View A&M University, Prairie View, Texas 77446, USA
E-mail: asamarasekara@pvamu.edu Tel: +1 936 261 3107; fax: +1 936 261 3117
_____________________________________________________________________________________
ABSTRACT: Renewable biomass based levulinic acid was converted to 5-methyl-2-pyrrolidone
in 94 % yield by a Raney-Ni catalyzed process using ammonium formate in aqueous medium
and heating at 180 °C for 3 h. The Raney-Ni could be reused for four catalytic cycles with about
10% loss in catalytic activity. In a similar reaction levulinic acid could be converted 1-
substituted-5-methyl-2-pyrrolidones in 90-95 % yield by using a mixture of formic acid and the
corresponding primary amine.
______________________________________________________________________________
KEYWORDS: levulinic acid; 5-methyl-2-pyrrolidone; -valerolactone; ammonium formate;
Raney-Ni
_____________________________________________________________________________
The current interest in sustainable carbon based chemical feedstocks and fuels has resulted a vast
expansion in research activities around cellulosic biomass derived C5-6 range compounds. Some
of the highly promising compounds in this series are furfural, 5-hydroxymethylfurfural (HMF),
levulinic acid (LA) and -valerolactone (GVL); most importantly these compounds can be
obtained via a series of catalytic transformations from the abundant polysaccharide fraction of
the lignocellulosic biomass 1.
4-Oxopentanoic acid or levulinic acid (LA) is particularly notable compounds in this inventory
due to its stability and potential to convert to many other useful feedstocks 2, 3, 4. In addition, LA
was listed as one of the top 12 most promising value added chemicals from biomass by the
5
Biomass Program of the US Department of Energy (DOE) in 2004 and also continues to rank
6
highly in more recent reviews of major bio-refinery target products . These value added

2
chemicals are molecules with multiple functional groups that possess the potential to be
5
transformed into new families of useful molecules . The twelve sugar-based building blocks in
the DOE analysis are: 1,4-diacids (succinic, fumaric and malic), 2,5-furan dicarboxylic acid, 3-
hydroxy propionic acid, aspartic acid, glucaric acid, glutamic acid, itaconic acid, levulinic acid,
5
3-hydroxybutyrolactone, glycerol, sorbitol, and xylitol/arabinitol . Although the current global
LA production is around 2600 tons/year, it is expected to grow in the coming years, particularly
due to the introduction of the Biofine process, which has been projected to lower the production
7
costs to as low as US $ 0.04–0.10 per lb . This versatile C-5 keto-acid can be used in the
synthesis of a range of useful chemicals such as γ-valerolactone, 2-methyl tetrahydrofuran,
acrylic acid, 1,4-pentanediol, β-acetylacrylic acid, α-angelica lactone, δ-amino levulinic acid, etc.
7, 8
and some of these compounds have been used for the preparation of polymers and fuel
precursors 9, 10, 11. Additionally, our recent studies have revealed a new route for the preparation
of a renewable C-7 polymer building block by aldol condensation between LA and glyoxylic
12
acid as well
.
The catalytic reduction of LA using noble metal catalysts and hydrogen gas is the well
established route for the preparation of another widely studied feedstock γ-valerolactone. The
analogous noble metal catalyzed process using a mixture of hydrogen and ammonia gases is
known to give the nitrogen analog of GVL 5-methyl-2-pyrrolidone (MPD). Similar to GVL the
pyrrolidones are also useful compounds, especially N-alkyl-5-methyl-2-pyrrolidones have a
wide diversity of applications, such as the use as an alternative to common solvent N-methyl-2-
pyrrolidone (NMP), surfactants, and important intermediates in the synthesis of agricultural
13,
bioactive compounds and pharmaceuticals
14. In addition, MPD is used as an important
constituent in many cleaning agents, refrigerants, air conditioning lubricants, inks and in aerosol
15
formulations . The patented method for producing MPD from LA using H2-NH3 mixture and
noble metal catalysts have several drawbacks such as the requirement of a high excess of H2 gas,
expensive noble metals, hazardous organic solvents, and limited selectivity for the formation of
the expected product when aryl amines are used in place of ammonia 13, 14. The most widely
used noble metal catalysts in this technique are Pt/C, Pd, Ru 16, Ru/C 14, Ir 17, and [Ru(p-
cymene)Cl2]2 18, 19. The polymeric ruthenium porphyrin-functionalized carbon nanotubes (Ru-
PP/CNTs) prepared by the metalation of polymeric porphyrin-functionalized carbon nanotubes

3
with Ru3(CO)12, has also been used in the synthesis of pyrrolidone derivatives from ethyl
levulinate, primary amines and hydrogen gas 20.
A few research groups have studied the possibility of reductive amination of levulinic acid using
transfer hydrogenation, without using hydrogen gas as the H atom source, especially using Ru
and Au based catalysts 19, 21. Du and co-workers developed the use of gold deposited on ZrO2 as
the catalyst, where they reported a one pot process requiring only formic acid, ammonia or
primary amines, and the Au catalyst to convert levulinic acid directly into the corresponding
pyrrolidones 21. In another example of transfer hydrogenation, Sun et al. used Ru based catalyst
fabricated via self-assembly from a p-phenylene-bridged bis-benzimidazolium salt with metal
precursors, where ammonium formate was used to prepare 5-methyl-2-pyrrolidone at a 0.15
mol% catalyst loading 22.
Our interest in upgrading biomass derived renewable feedstocks to value added chemicals,
23, 9, 24
polymeric materials and renewable fuels
has led us to study the use of ammonium
formate and Raney-Ni as the catalyst in reductive amination of levulinic acid to produce 5-
methyl-2-pyrrolidone. This method has certain advantages since ammonium formate is attractive
as a convenient H, N source; avoids the use of hydrogen, ammonia gases and relatively
abundant, inexpensive Ni is used in comparison to expensive Au or Ru noble metal catalysts
used in earlier studies. In this publication we report the use of Raney-Ni catalyst in reductive
amination of levulinic acid under thermal and microwave conditions to produce 5-methyl-2-
pyrrolidone as shown in figure 1; where the Ni catalyst could be reused without appreciable loss
in activity as well. In addition we have studied the possibility of using a mixture of primary
amines and formic acid to produce 1-substituted-5-methyl-2-pyrrolidones from levulinic acid by
Raney-Ni catalyzed reactions under thermal conditions as shown in figure 2.
O
HCO2NH4
+
O
O
N
H
O
OH
O
Raney-Ni, H2O
1
2
3
Figure 1. Raney-Ni catalyzed conversion of levulinic acid (1) to 5-methyl-2-pyrrolidone (2) and
-valerolactone (3) using ammonium formate as the hydrogen and nitrogen source

4
O
HCO2H, R-NH2
Raney-Ni, H2O
O
N
R
OH
4a, R = CH3-
4b, R = C6H5-
O
1
4c, R = p-CH3-C6H4-
Figure 2. Raney-Ni catalyzed conversion of levulinic acid (1) to 1-substituted, 5-methyl-2-
pyrrolidones (4a-c) using formic acid and primary amines
In our initial experiment (Table 1, entry 1) on Raney-Ni catalyzed reductive amination of
levulinic acid we have heated equimolar amounts of LA and HCO2NH4 at 120 °C for 20 h in a
closed high pressure Teflon reactor. The experimental details are in the supplementary data (SD)
associated with the article. This experiment gave only a low 40% conversion of levulinic acid
and produced a mixture of 5-methyl-2-pyrrolidone (48%) and -valerolactone (36%). Then
increase in the amount of ammonium formate to two equivalents improved the levulinic acid
conversion to 63% as shown in entry 2. The complete conversion of LA was possible with four
equivalents of HCO2NH4 at 160 °C, but gave a mixture of 2 and 3 (entry 3). Further increase in
temperature to 180 °C and a reaction time of 3 h gave the complete suppression of the -
valerolactone (3) formation, giving 5-methyl-2-pyrrolidone (2) in 94% yield (entry 4). This
reaction producing 2 as the sole product may be due to the rapid decomposition of four
equivalents of HCO2NH4 to NH3, H2 and CO2 at 180 °C and complete conversion of LA to its
ammonium salt at the initial stage of the reaction. As a comparison, we have tested the reaction
without adding any Raney-Ni catalyst as well (entry 5); this experiment gave only a low 15%
conversion of LA after 3 h at 180 °C. Furthermore, we have studied the possibility of heating the
reaction mixture using microwaves as shown in entry 6. This experiment gave a poor 11%
conversion after heating over five 10s microwave pulses, but producing only 5-methyl-2-
pyrrolidone (2) as the sole product.
Table 1. The LA : HCO2NH4 used, catalyst, reaction condition, levulinic acid conversion (%),
product yield based on LA reacted (%) and carbon balance (%) in Raney-Ni catalyzed
conversion of levulinic acid to 5-methyl-2-pyrrolidone (MPD, 2) and -valerolactone (GVL, 3).

5
1.0 mmol levulinic acid (LA) and 2.00 mL of water were used in all experiments. a levulinic acid
b
conversion % = (levulinic acid used - levulinic acid unreacted)/ levulinic acid used X 100;
Yield was calculated using: Yield % = (products detected/ levulinic acid reacted) X 100;
c
Carbon balance determined on the basis of 5-methyl-2-pyrrolidone (MPD, 2) and -valerolactone
(GVL, 3) products
Entry
LA :
HCO2NH4
Raney - Ni
catalyst
(mg/mmol
of LA)
Reaction
condition
LA
conversiona
(%)
Product yield
based on LA
reacted (%)b
Carbon
balancec
(%)
MPD
(2)
48
GVL
(3)
36
30
28
-
1
2
3
4
5
6
1 : 1
1 : 2
1 : 4
1 : 4
1 : 4
1 : 4
20
20
20
20
-
Oven, 120 °C, 20 h
Oven, 120 °C, 20 h
Oven, 160 °C, 3 h
Oven, 180 °C, 3 h
Oven, 180 °C, 3 h
MW (920W), 5 x 10s
40
63
84
82
88
94
91
80
52
100
100
15
60
94
68
23
-
20
11
80
Table 2. The LA : HCO2H : R-NH2 used, reaction condition, levulinic acid conversion (%),
product, yield (%) and carbon balance (%) in Raney-Ni catalyzed conversion of levulinic acid to
1-substituted-5-methyl-2-pyrrolidones (4a-c) under oven heating conditions.
Levulinic acid (1.0 mmol), 20 mg Raney-Ni and 2.00 mL of water were used in all experiments.
a levulinic acid conversion % = (levulinic acid used - levulinic acid unreacted)/ levulinic acid
used X 100; b Yield was calculated using: Yield % = (products detected/ levulinic acid reacted)
c
X 100; Carbon balance determined on the basis of 1-substituted-5-methyl-2-pyrrolidone
products (4a-c).
Entry
R-NH2
(R - )
LA : FA : R-NH2
Reaction
condition
LA
conversiona
(%)
Product yield
based on LA
reacted (%)b
4a, 48
Carbon
balancec
(%)
1
CH3-
1 : 1 : 1
120 °C, 20 h
46
48
2
3
4
5
CH3-
C6H5-
1 : 4 : 1
1 : 1 : 1
1 : 4 : 1
1 : 4 : 1
180 °C, 3 h
120 °C, 20 h
180 °C, 6 h
180 °C, 6 h
100
62
4a, 95
4b, 55
4b, 92
4c, 90
95
55
92
90
C6H5-
100
100
p-CH3-C6H4-
The results from Raney-Ni catalyzed synthesis of 1-substituted-5-methyl-2-pyrrolidones (4a-c)
from levulinic acid are shown in Table 2. The initial experiments using LA : HCO2H : CH3-NH2
1 : 1 : 1 gave only a low 46% conversion of levulinic acid as shown in entry 1 in Table 2.

6
However the increase in formic acid (FA) content gave the complete conversion of levulinic acid
and an excellent yield of 1,5-dimethyl-2-pyrrolidone as shown in entry 2. As with methylamine
the experiment with aniline using LA : HCO2H : CH3-NH2 1 : 1 : 1 gave a low LA conversion
and a product yield (entry 3). However, an increase in formic acid content produced high yields
of the corresponding 1-substituted-5-methyl-2-pyrrolidones from aniline as well as from p-
toluidine as shown in entries 4 and 5.
Figure 3. The percent yields of 5-methyl-2-pyrrolidone (2) produced in reusing Raney-Ni
catalyst in conversion of levulinic acid to 5-methyl-2-pyrrolidone (2) using ammonium formate
as the H and N source
The percent yields of 5-methyl-2-pyrrolidone (2) produced in reusing the Raney-Ni catalyst in
reductive amination of LA with ammonium formate under thermal conditions is shown in figure
3. This experiment shows that catalyst can be reused for four cycles with about a 10% loss in
catalytic activity of the Raney-Ni without any special cleaning or regeneration of the catalyst
surface. The reuse experiment details are in the supplementary data (SD).

7
HCO2NH4
H2 NH3
+
CO2
OH
+
O
_
O
O
+
- H2O
ONH4
NH2
O
O
O
1
- H2O
- H2O
O
H2
H2
Raney-Ni
O
O
O
O
N
N
H
O
Raney-Ni
3
2
Figure 4. The proposed reaction pathways for the Raney-Ni catalyzed conversion of levulinic
acid (1) to 5-methyl-2-pyrrolidone (2) and -valerolactone (3) using ammonium formate
The proposed reaction pathways for the Raney-Ni catalyzed transformations of levulinic acid
with ammonium formate are shown in figure 4. The ammonium formate may decompose to a gas
25
mixture of H2, NH3 and CO2 at the reaction temperature and the ammonia formed reacting
with levulinic acid gives the ammonium salt. The dehydration of the salt can lead to the amide,
which undergoes a reversible cyclization to 3,4-dihydro-5-methyl-2H-pyrrol-2-one. The Raney-
Ni catalyzed reduction of this intermediate product by hydrogen present in the reactor may give
the 5-methyl-2-pyrrolidone (2). The alternative path of reversible cyclization of levulinic acid to
5-methyl-2(3H)-furanone and reduction of this intermediate gives the -valerolactone byproduct,
especially at lower temperatures.
In conclusion, we have shown that levulinic acid can be converted to 5-methyl-2-pyrrolidone in
94 % yield by using four equivalents of ammonium formate and Raney-Ni as the catalyst in
water at 180 °C. Under similar reaction conditions levulinic acid could be converted 1-
substituted-5-methyl-2-pyrrolidones in 90-95 % yield by using a mixture of formic acid and
corresponding primary amines. This technique provides a simple, single reactor process to
produce 5-methyl-2-pyrrolidone and its N-substituted derivatives from levulinic acid under mild
conditions and the new method has certain advantages such as: no external hydrogen source or
expensive noble metal catalysts are required. The Ni-catalyst could be reused for four catalytic
cycles with a small loss in catalytic activity. In addition the presented method has certain safety

8
advantages over the patented method, which requires the heating of a H2-NH3 gas mixture at
high pressures of 7-9 MPa 13, 14
.
Acknowledgments
We thank NSF grants CBET-0929970, CBET-1336469, HRD-1036593, and USDA grant CBG-
2010-38821-21569 for financial support.
Supplementary data (SD)
Supplementary data associated with this article can be found at: xxx: xxx

9
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Highlights
Raney-Ni catalyzed conversion of levulinic acid to 5-methyl-2-pyrrolidone using
ammonium formate as the H and N source
Ananda S. Amarasekara*, Yen Maroney Lawrence
_____________________________________________________________________________________
 Reaction of levulinic acid with HCO2NH4 and Raney-Ni gives 5-methyl-2-pyrrolidone
 Levulinic acid, HCO2H, R-NH2 and Raney-Ni gives 1-substituted-5-Me-2-pyrrolidones
 Ni-catalyst could be reused for four cycles with 10% loss in catalytic activity

12
Graphical Abstract
Raney-Ni catalyzed conversion of levulinic acid to 5-methyl-2-pyrrolidone using
ammonium formate as the H and N source
Ananda S. Amarasekara*, Yen Maroney Lawrence
_____________________________________________________________________________________
O
HCO2NH4
O
N
H
OH
Raney-Ni, H2O
180oC, 3 h
O