Application of γ-Valerolactone as an Alternative Biomass-Based Medium for Aminocarbonylation Reactions

Article abstract of DOI:10.1002/cplu.201600389

γ-Valerolactone (GVL) was proposed as a renewable, nontoxic reaction medium with negligible vapor pressure for homogeneous Pd-catalyzed aminocarbonylation reactions. Iodobenzene as a model substrate and its 4-substituted derivatives were converted to the corresponding 2-ketocarboxamides with high conversions and chemoselectivities in γ-valerolactone. The effect of carbon monoxide pressure and reaction temperature on the conversion and selectivities were studied in the range 1–50 bar and 25–100 °C, respectively. The highest conversion and selectivity was achieved at 25 bar and 50 °C for iodobenzene in GVL for 24 h.

Full text of DOI:10.1002/cplu.201600389

Accepted Article
Title: Application of -valerolactone as an alternative biomass-based medium for ami-
nocarbonylation reactions
´
¨
´
´
´
´
Authors: Diana Marosvolgyi-Hasko; Blanka Lengyel; Jozsef M Tukacs; Laszlo
´
Kollar; Laszlo T Mika
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Application of -valerolactone as an alternative biomass-based
medium for aminocarbonylation reactions
Diána Marosvölgyi-Haskó,[b] Blanka Lengyel,[a] József M. Tukacs,[a] László Kollár,[b]
and László T. Mika*[a]
6
]
Abstract: -Valerolactone was proposed as a renewable, non-toxic
dioxide[
have been successfully introduced in the
reaction medium having negligible vapor pressure for homogeneous
homogeneous catalysis. For the last decades, trends have been
moved towards to identification of bio-based reaction media for
organic synthesis and catalysis for example glycerol[7] and its
Pd-catalyzed aminocarbonylation reactions. Iodobenzene as
a
model substrate and its 4-substituted derivatives were converted to
the corresponding 2-ketocarboxamides with high conversion and
chemoselectivities in -valerolactone. The effect of carbon monoxide
pressure and reaction temperature on the conversion and
selectivities were studied in the range of 1–50 bar and 25–100 °C,
respectively. The highest conversion and selectivitiy was achieved at
25 bar and 50 °C for iodobenzene in GVL for 24 h.
8
]
9 ]
derivatives,[
or ethyl lactate.[
Consequently, in the
development of alternative, non fossil-based strategies to
produce value-added chemicals in the future, the selection of
solvents having environmental friendly properties, i.e. low vapor
pressure and toxicity is fundamentally important and even could
be a key part of cleaner and greener chemical processes.
Among the recently characterized biomass-based platform
molecules,[10] -valerolactone (GVL) has been received an ever
increasing interest since it was firstly proposed as a sustainable
liquid by Horváth in 2008.[11] Due to its attractive physical and
chemical properties, several applications of GVL were
demonstrated in the last few years. It can be produced from
cellulose[ 12 ] and used for the production of alkanes and
alkenes,[13] transportation fuels,[14] fine chemicals,[15] illuminating
and lighter fluid,[16] etc. GVL is liquid in wide temperature range
and has negligible vapor pressure[17] avoiding its emission to the
atmosphere. It occurs in fruits and wines,[18] non-toxic and has
been utilized by food industry. Recently, the utilization of GVL as
a biomass-based solvent has received an increasing attention,
as well. We have shown that it can be a reaction medium for
selective hydrogenation of levulinic acid to 4-hydroxyvaleric
acid.[ 19 ] Horváth et al. demonstrated that the dehydration of
various carbohydrates could be performed in GVL under strong
acidic environment in temperature range 70–170 °C.[20] It was
recently shown that GVL with co-solvents can form as an
efficient media for dissolution of various lignins at moderate
temperature (40–70 °C)[21] as well as enhance the hydrolysis of
Introduction
The chemical industry, which produces enormous
amount of value-added chemicals highly depends on fossil
based resources. The integrated processing of crude oil
continuously provides bulk chemicals including conventional
organic solvents for both petrochemical and fine chemical
industries. Although, it is hard to estimate the depletion of crude
oil, the environmental and sustainability issues have increased
attentions toward the identifications and applications of
alternative resources and renewable building blocks from which
the selection of appropriate solvents is also highly desired. The
rapidly expanding research activity on biomass conversion, as
the most preferred alternative solution has identified several
renewable platform chemicals that could replace fossil based
ones as well as could act as a part of alternative solvents. The
industrial activities involving solvents result in the release of
volatile organic compounds (VOCs) including conventional
solvents into the environment for example for EU28 over 7
million tons annually.[1] Some of them have been leading to
serious environmental concerns, moreover, economic issues.
According to FDA guidelines[ 2 ] utilization of several "classic"
organic solvents must be avoided (e.g. benzene and chlorinated
hydrocarbons) or limited (e.g. toluene), just to name a few.
Focusing on the development of environmentally benign
chemical transformations, several alternative solvents e.g
water,[3] fluorous4 and ionic liquids (IL),5 and supercritical carbon
[22]
monosaccharides and lignocellulosic biomass over 120 °C.
Dumesic revealed that the levulinic acid and GVL can be
produces from cellulose in a GVL-based biphasic system
operating high temperatures (> 180 °C).[23 ] Vaccaro and co-
workers showed that it could be an excellent solvent for
heterogeneous coupling reactions operating in wide temperature
range (50–150 °C).[ 24 , 25 , 26 ] The Pt-catalyzed enantioselective
hydroformylation of styrene was also successfully carried out in
GVL in a range of 40–130 °C without significant changes of
enantiomeric excess.[27]
The carbonylation reactions have indisputable role in
homogeneous transition metal catalysis and serve as a facile
[a]
[b]
Blanka Lengyel, József M. Tukacs, Dr. László T. Mika
Department of Chemical and Environmental Process Engineering,
Budapest University of Technology and Economics
Műegyetem rkp. 3, Budapest, H-1111, Hungary
e-mail: laszlo.t.mika@mail.bme.hu
28
]
method for carbon-carbon bond formation.[
Among
carbonylations, alkoxy- and aminocarbonylation has gained a
special importance. Since the early discovery of Heck et al[29] on
the Pd-catalyzed carbonylation of haloarenes, hundreds of
examples were published describing structure–reactivity,
structure–selectivity correlations and demonstrating synthetic
applications.[30] Various structures were functionalized using a
Diána Marosvölgyi-Haskó, Dr. László Kollár
Department of Inorganic Chemistry, University of Pécs and János
Szentágothai Research Center and MTA-PTE Research Group
for Selective Chemical Syntheses,
Ifjúság u. 6.; Pécs, H-7624, Hungary
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10.1002/cplu.201600389
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broad variety of alcohols and amines as O- and N-nucleophiles,
respectively. In this way, esters and carboxamides that are not
available by using conventional synthetic routes have been
utilization of GVL opens
carbonylation reactions.
a
greener alternative way in
synthesized representing
a diversity of products in both
laboratory and industrial requirements. As one of the principal
side-reaction of carboxamide formation, the seminal work of
Yamamoto et al on double carbonylation in the presence of
amines, i.e. the formation of 2-ketocarboxamides has to be
Results and Discussion
The vapor pressure as a key property of a volatile organic
compound (VOC)[45] is crucial for application of a substance as a
solvent. In comparison the temperature dependence of vapor
pressure of solvents that commonly used for aminocarbonylation
reactions to GVL's, it can be stated that the replacement of
these media with GVL could result in an environmental benign
catalytic system. The vapor pressures of GVL in the temperature
range of aminocarbonylation reactions are two orders of
magnitude less than DMF or toluene (Figure 1).[46]
In order to demonstrate the applicability of GVL as a
reaction medium for Pd-catalyzed aminocarbonylation of
iodobenzene and its derivatives in the presence of Et3N as a
base, we applied tBuNH2 as a nucleophile. Firstly, iodobenzene
(Scheme 1, 1a, 1 mmol) was carbonylated in the presence of
catalyst in situ formed from 0.025 mmol of Pd(OAc)2 and 0.05
mmol of PPh3, and 0.5 mL of Et3N in 10 mL of DMF as a
reference reaction at 50 °C. When 1 bar of CO was applied,
[
31 ]
highlighted.
Thus, aminocarbonylation is of utmost
importance in the synthesis of carboxamides and
ketocarboxamides.
Table 1. Toxicity data and solvatochromic parameters of solvents used for
aminocarbonylation reactions.
Toxicity data
Kamlet-Taft Parameters[32]
Solvent[a]
LD50 oral rat (mg/kg)
[a]

[b]

* [c]
DMF
2800[33]
5000[34]
5200[35]
175[36]
0.00
0.00
0.00
0.19
0.06
0.00
0.00
0.69
0.11
0.37
0.40
0.48
0.55
0.60
0.88
0.54
0.55
0.75
0.67
0.58
0.83
Toluene
1,4-dioxane
acetonitrile
2-butanone
THF
2900[37]
1650[33]
8800[11]
GVL
[a] hydrogen-bond donating ability (acidity), [b] hydrogen-bond accepting
ability (basicity), [c] polarity/polarizability
Although, the aminocarbonylation reactions are routinely
performed in conventional organic solvents such as N,N-
dimethylformamide (DMF),[ 38 ] toluene,[ 39 ] 1,4-dioxane,[ 40 ] 2-
butanone,[41] acetonitrile[42] and tetrahydrofurane (THF),[43] DMF
has been identified as best medium for Pd-catalyzed reactions.
However, the toxicity of the conventional solvents is significantly
higher compared to biomass-based alternative -valerolactone
(Table 1.). The oral LD50 value of GVL measured on rat is ca.
three times higher that that of DMF. In addition, GVL does not
form any measurable amount of peroxide during its storage
under air for weeks,[11,44] which is also crucial safety issue for
handling and laboratory use. We selected solvatochromic
Kamlet-Taft parameters concerning hydrogen-bond donating
ability (acidity, ), hydrogen-bond accepting ability (basicity, )
and polarity (*) to compare (Table 1.) the various solvents
utilized for aminocarbonylation. It shows that GVL has similar
solvatochromic properties to DMF. Both  and * parameters are
very close to each other. It has to be also emphasized that to the
best of our knowledge, no carbonylation reactions in GVL as a
solvent has been demonstrated yet.
Figure 1. Vapor pressures of commonly used solvents and GVL.
NHtBu
NHtBu
+
C
O
O
O
I
C
C
X
tBu-NH2
1-40 bar CO, 50 °C
Pd(OAc)2 / PPh3
Solvent: GVL
X
1
X
2
3
X = H (a), NH2 (b), OH (c), tBu (d), CH3 (e), iPr (f), Ph (g), F (h), Cl (i)
Br (j), COOCH3 (k), C(O)CH3 (l), CF3 (m), CN (n)
We report here the application of GVL as a proposed non-
toxic, polar and renewable reaction medium for palladium-
catalyzed aminocarbonylation of iodobenzene and its derivatives
at different pressures and temperatures. We do think that this
Scheme 1. Aminocarbonylation of 4-substituted iodobenzenes with tert-
butylamine in GVL.
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Table 2. Aminocarbonylation of iodobenzene (1a) in the presence of Pd(OAc)2/2 PPh3 in situ catalyst using tert-butylamine as an N-nucleophile in conventional
organic solvents and GVL [a]
Conversion[b]
pCO
Ratio of the carbonylated products[b]
Carboxamide (2a) Ketocarboxamide (3a)
#
Solvent
1 bar
10 bar
96
1 bar
42
56
43
68
0
10 bar
1 bar
58
44
57
32
0
10 bar
70
1
2
3
4
5
DMF
98
13
44
21
0
30
0
Toluene
99
100
100
98
Acetonitrile
1,4-dioxane
2-butanol[c]
86
0
99
2
84
0
11
6
GVL
78
93
30
6
70
94
[a] Reaction conditions: 1 mmol iodobenzene, 3 mmol of tBuNH2, 0.025 mmol of Pd(OAc)2, 0.05 mmol of PPh3, 0.5 mL of Et3N, solvent: 10 mL, T = 50 oC, t = 24 h
[b] determined by GC-MS. [c]: The main product (89%) was 2-butyl benzoate.
that no 1,4-dicarboxamide formation was detected even with 4-
98% conversion was achieved with 42% selectivity of
carboxamide (2a) (58 % 2-ketocarboxamide (3a)) for 24 h. By
increasing the carbon monoxide pressure to 10 bar 96%
conversion was observed under identical conditions. However,
the selectivity of carboxamide decreased to 30% indicating that
the double carbon monoxide insertion leading to 3a was slightly
favoured upon an increased carbon monoxide pressure. (Table
2, entry 1). In order to compare the commonly used reaction
media to GVL, the reaction was repeated in conventional
organic solvents generally utilized for aminocarbonylation (Table
2, entries 2–5). The conversions were moderate at atmospheric
pressure; however, when 10 bar CO was applied comparable
values were achieved. It should be noted that outstanding
selectivity was obtained in toluene and acetonitrile under 10 bar
of CO. Expectedly, in 2-butanol as O-nucleophile the main
product was 2-butyl benzoate as alkoxycarbonylated product
(Table 2, entry 5). By replacing the solvent to GVL, a slightly
lower conversion (78 %) with comparable selectivity were
obtained for iodobenzene (1a) at atmospheric pressure of CO
for 24 h. However, the conversion of (1a) and chemoselectivity
to 2-ketocarboxamide (2a) was increased enormously providing
almost perfect selectivity to the double carbonylated product 3a
when 10 bar CO pressure was applied. (Table 2, entry 6 and
Table 3, entry 1). It should be noted that iodobenzene (1a) can
be completely converted to 2a and 3a in up to 72 h even under
bromoiodobenzene (1j) possessing bromoarene functionality as
well. This reaction might be of synthetic importance since the 4-
bromocarboxamide (2j) and the 4-bromoketocarboxamide (3j)
products can be further reacted towards 1,4-functionalized
derivatives.
Mixtures
of
carboxamides
(2b-2n)
and
ketocarboxamides (3b-3n) were formed in most cases. It should
be emphasized that 2-ketocarboxamides, formed in double CO
insertion, prevailed in all cases. Interestingly, while the
chemoselectivities towards 2-ketocarboxamides at 10 bar CO
could be supported by electron-releasing groups (see, for
instance, entries 1, 3, 6), the opposite trend can be observed in
case of electron-withdrawing groups (see, for instance entries 19,
21). These two cases can be exemplified by the methyl group
(p= -0.17) and the trifluoromethyl group (p= +0.54), where the
chemoselectivity towards the corresponding ketocarboxamides
(3e and 3m) was increased from 83% to 97%, and decreased
from 82% to 63%, respectively. However, when 1k and 1n were
carbonylated, the formation of ketokarboxamide was favored at
10 bar.
The high ketocarboxamide selectivity obtained under mild
conditions could substantially be further improved by increasing
CO pressure. Accordingly, the effect of carbon monoxide
pressure on the conversion and selectivity was investigated in
the range of pCO = 1–50 bar by reacting of 1 mmol iodobenzene
(1a) and 3 mmol of tBuNH2 in the presence of catalyst formed in
mild conditions without significant changes in selectivity (Table 3, situ from 0.025 mmol of Pd(OAc)2 and 0.05 mmol of PPh3 in a
entry 2).
GVL proved to be excellent solvent also for the conversion
mixture of 0.5 mL of Et3N and 10 mL of GVL at 50 oC (Figure 2.).
Both conversion of 1a and selectivity of ketocarboxamide were
slowly increased by increasing of CO pressure reaching a
maximum at ca. 25 bar. Working above 25 bar the conversion
decreased significantly at higher pressures. It can be assumed
that the higher CO concentration could increase the number of
coordinated carbonyl ligand on Pd center resulting in lower
concentration of coordinatively unsaturated catalytically active
species. Similar observations were reported for SILP-Pd
assisted aminocarbonylation of iodobenzene and synthesis of
ferrocene amides.[47,48] Selectivities towards the formation of the
of series of 4-substituted iodobenzenes (Scheme 1, 1b-1n) to
the corresponding 4-substituted carboxamide (Scheme 1, Table
3, 2b-2n) and ketocarboxamide (Scheme 1, 3b-3n). With the
exception of 4-iodoaniline (1b) and 4-iodophenol (1c) good to
excellent activities were observed, i.e., iodoarenes were
converted to the corresponding aminocarbonylated products in
high yields. The reaction is highly selective concerning
iodoarene carbonylations showing good functional group
tolerance. No side-reactions could be observed using either 1b,
1c or the halide substituted substrates (1h-1j). It is remarkable
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Table 3. Aminocarbonylation of 4-substituted iodobenzenes (1a-1n) in the presence of Pd(OAc)2/2 PPh3 in situ catalyst using tert-butylamine as an N-
nucleophile in GVL [a]
Substrate (1)
Conversion[b]
pCO
Ratio of the carbonylated products[b]
Carboxamide (2) Ketocarboxamide (3)
10 bar
Time
(h)
#
Code
X
1 bar
78
10 bar
1 bar
30 (2a)
39 (2a)
11 (2b)
14 (2c)
0 (2d)
1 bar
70 (3a)
61(3a)
89 (3b)
86 (3c)
100 (3d)
83 (3e)
74 (3e)
90 (3f)
80 (3g)
69 (3g)
91 (3h)
78 (3h)
92 (3i)
87 (3i)
84 (3j)
74 (3j)
83 (3k)
83 (3k)
80 (3l)
10 bar
1
2
a
a
b
c
d
e
e
f
H
H
24
72
24
24
24
24
96
24
24
48
24
48
24
48
24
48
24
48
24
93
-
6 (2a)
94 (3a)
100
38
3
NH2
OH
62
19
26
94
-
2 (2b)
3 (2c)
0 (2d)
3 (2e)
98 (3b)
97 (3b)
100 (3d)
97 (3e)
4
15
5
tBu
20
6
CH3
CH3
iPr
68
17 (2e)
26 (2e)
10 (2f)
20 (2g)
31 (2g)
9 (2h)
7
91
8
16
59
90
-
4 (2f)
96 (3f)
84 (3g)
9
g
g
h
h
i
Ph
74
16 (2g)
10
11
12
13
14
15
16
17
18
19
Ph
98
F
58
92
-
2 (2h)
20 (2i)
3 (2j)
7 (2k)
35 (2l)
98 (3h)
80 (3i)
97 (3j)
93 (3k)
65 (3l)
F
93
22 (2h)
8 (2i)
Cl
74
76
-
i
Cl
100
73
13 (2i)
16 (2j)
26 (2j)
17 (2k)
17 (2k)
20 (2l)
j
Br
95
-
j
Br
100
91
k
k
l
COOCH3
COOCH3
C(O)CH3
100
-
100
91
99.8
20
21
22
23
24
l
C(O)CH3
CF3
48
24
48
24
48
100
74
-
73
-
24 (2l)
18 (2m)
21 (2m)
39 (2n)
31 (2n)
76 (3l)
82 (3m)
79 (3m)
61 (3n)
69 (2n)
m
m
n
37 (2m)
19 (2n)
63 (3m)
81 (3n)
CF3
94
CN
87
100
-
n
CN
100
[a] Reaction conditions (unless otherwise stated): 1 mmol substrate (1a-1n), 3 mmol of tBuNH2, 0.025 mmol of Pd(OAc)2, 0.05 mmol of PPh3, 0.5 mL of Et3N, 10
mL of GVL, T = 50 oC. [b] determined by GC-MS.
corresponding ketocarboxamides were also increased; however,
its decreasing was not detected at higher pressures.
is important to emphasize that the thermal stability of GVL is
limited by its ring-opening to form 3-pentenoic acids, which can
undergo further isomerization. However, these reactions as well
as the formation of -angelicalactone could take place at high
temperatures (> 160 °C).[13b, 49 ] Expectedly, our GC-MS and
NMR analysis did not indicate any degradation of GVL in the
temperature range used for aminocarbonylation reactions.
The reproducibility of catalytic conversions was confirmed
by repeating the experiment under 10 bar of CO using
The effect of reaction temperature on the conversion and
selectivity was also investigated in the range of 25–100 °C.
While, the almost complete conversion could be achieved at
75 °C for 24 h, the selectivity towards formation of keto-
carboxamide started to decrease over 50 °C (Figure 3.). It is in
good agreement with observation reported for conversion
iodoferrocene under 40 bar of CO at different temperatures.[48] It
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iodobenzene (1a) as a substrate at 50 °C (Table 2, entry 1.).
Conversion of 92 % with same selectivities was achieved in the
repeated measurement.
Experimental Section
Iodobenzene and its derivatives (1b-1n), DMF, toluene,
and GVL were obtained from Sigma-Aldrich Kft., Budapest,
Hungary. GC analyses were performed on a HP 5890N
instrument with HP-5 capillary column (15 m x 0.25 m) using H2
as a carrier gas. For the analysis, 10 μL of reaction mixture was
dissolved in 1 mL of methylene chloride followed by the addition
of 10 μL toluene as internal standard. GVL was purified by
distillation at reduced pressure (4–5 Hgmm) at 75−80 °C[17] and
stored on a molecular sieve under N2.
In a typical carbonylation reaction performed at atmospheric
carbon monoxide pressure Pd(OAc)2 (5.6 mg, 0.025 mmol),
triphenylphosphine (13.2 mg, 0.05 mmol), 4-substituted iodobenzene
(1.00 mmol), tert-butylamine (0.315 mL, 3.00 mmol), and
triethylamine (0.5 mL) were dissolved in the corresponding solvent
(10 mL) (except GVL ) under argon in a 100 mL three-necked bottle
with a reflux condenser connected to a balloon on the top of it. The
atmosphere was changed to carbon monoxide. The reaction was
conducted for the given reaction time (Table 3) upon stirring at 50
oC. The reaction mixture was analysed by TLC as well as by GC and
GC-MS. The solvent was evaporated under reduced pressure. The
waxy residue was dissolved in chloroform (20 mL), then washed with
water (20 mL), twice with 5% aq HCl (20mL), satd aq NaHCO3
(20mL) and satd. aq. brine (20mL). The organic phase was dried
over Na2SO4, filtered and evaporated to a solid material.
Figure 2. Effect of carbon monoxide pressure on the conversion of
iodobenzene.
To the reaction mixtures dissolved in GVL, 50 mL of
hexane and 100 mL of water was added. The hexane phase
was separated and washed with water (100 mL). The organic
phase was dried over Na2SO4, filtered and evaporated to a solid
material.
All compounds were subjected to column chromatography
(Silicagel 60 (Merck), 0.063-0.200 mm), EtOAc/CHCl3 or
hexane/EtOAc/CHCl3 eluent mixtures. Isolated yields from 5%
(2f) to 20% (2a) and from 33% (3n) to 68% (3d) (not optimized,
based on amount of the substrate used in atmospheric
experiments)
were
obtained
for
carboxamides
and
ketocarboxamides, respectively. The compounds gave identical
analytical data with those synthesized in conventional
procedure.[50]
In a typical high-pressure carbonylation experiment, the 25
mL high-pressure Hastelloy-C reactor (4742, Parr Inst. IL USA)
equipped with manometer, safety relief and magnetic stirring bar
using external heating (oil bath) was charged with 1 mmol
substrate, 3 mmol of tBuNH2, 0.025 mmol of Pd(OAc)2 as a
catalyst precursor, 0.05 mmol of PPh3, 0.5 mL of Et3N, and 10
mL of corresponding solvent resulting in a straw yellow solution.
The reaction mixture was pressurized with carbon monoxide
(99.9%) gas then heated up to 50 °C and stirred at 350 RPM.
After given reaction time, the reaction mixture was cooled down
to room temperature and the pressure was released in a well-
ventilated hood. The product mixture was analyzed by a GC or
GC-MS. The work-up of the reaction mixture containing GVL
solvent was identical to that described for atmospheric
experiments.
Figure 3. Effect of reaction temperature on the conversion of iodobenzene.
Reaction conditions: 1 mmol iodobenzene (1a), 3 mmol of tBuNH2, 0.025
mmol of Pd(OAc)2, 0.05 mmol of PPh3, 0.5 mL of Et3N, 10 mL of GVL, pCO
25 bar.
=
Conclusions
We demonstrated that GVL as a non-toxic and renewable
platform chemical can be used as alternative solvent for
palladium-catalyzed aminocarbonylation reactions opening a
greener procedure for this synthetically relevant transformation.
Various 4-substituted iodobenzenes were converted to the
corresponding 2-ketocarboxamides of synthetic importance in
GVL.
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The single and double carbonylated products (2a-n and
3a-n, respectively) show identical spectra with those obtained in
[15] a) M. Chalid, H. J. Heeres, A. A. Broekhuis, J. Appl. Polym. Sci. 2011,
123, 3556–3564. b) J. M. Tukacs, B. Fridrich, G. Dibó, E. Székely, L. T.
Mika, Green Chem. 2015, 17, 5189–5195.
conventional aminocarbonylation. [50]
[16] V. bos, M. . Lui, . . Mui, . . ong, L. . Mi a, L. i, .
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Entry for the Table of Contents
FULL PAPER
It was demonstrated that GVL as a
non-toxic and renewable platform
chemical can be used as alternative
solvent for palladium-catalyzed
aminocarbonylation reactions opening
a greener procedure for this
Diána Marosvölgyi-Haskó, Blanka
Lengyel, József M. Tukacs, László
Kollár, László T. Mika*
Page No. – Page No.
Application of -valerolactone as an
alternative biomass-based medium
for aminocarbonylation reactions
synthetically relevant transformation.
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