Rhodium-catalyzed hydroformylation in γ-valerolactone as a biomass-derived solvent

Article abstract of DOI:10.1016/j.jorganchem.2017.04.029

Rhodium-catalyzed hydroformylation of styrene, α-methylstyrene, dimethyl itaconate, and (R)-limonene was performed in gamma-valerolactone (GVL) as a proposed biomass-based environmentally benign solvent for hydroformylation referring to toluene as a generally used conventional solvent. Both achiral (triphenylphosphine, 1,3-bis(diphenylphoshino)propane) and enantiopure bidentate phosphine ligands ((S,S)-BDPP, (R)-BINAP, (R)-QUINAP, (R,R)-DIOP, (R_c),(S_p)-JOSIPHOS, (S)-SEGPHOS, (S)-(DM)-SEGPHOS) were investigated in in situ generated Rh-diphosphine catalyst systems. In general, the catalysts' activity in GVL was lower than in toluene; however, remarkable chemo- (>99%) and regioselectivities (>95%) were achieved in GVL under identical conditions. The BDPP-modified Rh-catalyst was recycled for three consecutive cycles; however a decrease in its activity was detected.

Full text of DOI:10.1016/j.jorganchem.2017.04.029

Accepted Manuscript
Rhodium-catalyzed hydroformylation in γ-valerolactone as a biomass-derived solvent
Péter Pongrácz, Brigitta Bartal, László Kollár, László T. Mika
PII:
S0022-328X(17)30267-X
10.1016/j.jorganchem.2017.04.029
JOM 19916
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 31 January 2017
Revised Date: 20 April 2017
Accepted Date: 21 April 2017
Please cite this article as: Pé. Pongrácz, B. Bartal, Láó. Kollár, Láó.T. Mika, Rhodium-catalyzed
hydroformylation in γ-valerolactone as a biomass-derived solvent, Journal of Organometallic Chemistry
(2017), doi: 10.1016/j.jorganchem.2017.04.029.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1
Rhodium-catalyzed hydroformylation in γ-valerolactone as a
2
3
4
5
biomass-derived solvent
Péter Pongrácz,b Brigitta Bartalb, László Kollár,b and László T. Mika,a,*
6
7
8
aDepartment of Chemical and Environmental Process Engineering, Budapest
University of Technology and Economics, Műegyetem rkp. 3., H-1111, Budapest,
Hungary.
bDepartment of Inorganic Chemistry, University of Pécs and János Szentágothai
Research Center and MTA-PTE Research Group for Selective Chemical Syntheses,
Ifjúság u. 6., H-7624, Pécs, Hungary.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
This paper is dedicated to Professor John A. Gladysz on the
occasion of his 65th birthday
Keywords
Alternative solvent, gamma-valerolactone, hydroformylation, homogeneous catalysis,
rhodium
Abstract
Rhodium-catalyzed hydroformylation of styrene, α-methylstyrene, dimethyl
itaconate, and (R)-limonene was performed in gamma-valerolactone (GVL) as a
proposed biomass-based environmentally benign solvent for hydroformylation
referring to toluene as a generally used conventional solvent. Both achiral
(triphenylphosphine, 1,3-bis(diphenylphoshino)propane) and enantiopure bidentate
phosphine ligands ((S,S)-BDPP, (R)-BINAP, (R)-QUINAP, (R,R)-DIOP, (Rc),(Sp)-
JOSIPHOS, (S)-SEGPHOS, (S)-(DM)-SEGPHOS) were investigated in in situ
generated Rh-diphosphine catalyst systems. In general, the catalysts' activity in GVL
was lower than in toluene; however, remarkable chemo- (>99%) and regioselectivities
(>95%) were achieved in GVL under identical conditions. The BDPP-modified Rh-
catalyst was recycled for three consecutive cycles; however a decrease in its activity
was detected.
1

ACCEPTED MANUSCRIPT
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
1. Introduction
Since the accidental discovery of hydroformylation (or oxo-synthesis)
concerning the cobalt-catalyzed Fischer-Tropsch reactions by Otto Roelen [1], the
highly chemo-, regio- and enantioselective hydroformylation of alkenes to aldehydes
has become one of the most important homogeneous transformations [2] even at
industrial scale [3]. Regarding the variation of the substrates, two major topics can be
distinguished i) hydroformylation of (terminal) alkenes with the aim of obtaining high
linear selectivity and ii) the highly regio- and enantioselective hydroformylation of
functionalized olefins to synthesize fine chemicals. The first group can be exemplified
by the large scale production of C9-C11, so-called "oxo" aldehydes or highly
regioselective hydroformylation of propene to n-butyraldehyde, which is the basic
compound of 2-ethylhexanol built into diisooctyl phthalate plasticizers. The small
scale enantioselective hydroformylation of vinylaromatics to 2-arylpropanals, the
intermediate of non-steroidal anti-inflammatory drugs (NSAIDs) can be distinguished
as an example for the second one [4]. Although, several industrial oxo-plants utilized
both non-modified Co- and Rh-catalysts [4], to improve activity and selectivity
hundreds of modified Co-, Rh- and Pt-containing catalysts were developed and some
of them have been introduced on industrial scale. While, the large scale industrial
oxo-synthesis is continuously performed in refinery olefin mixtures, the small scale
hydroformylations very often take place in the presence of various conventional
organic solvents such as benzene, toluene, or C6-C10 alkane [2], from which several
have high toxicity, vapour pressure even at high temperature, and significant negative
impact on the environment.
As for the technological, economic and environmental aspects of
hydroformylation, several improvements have been completed including development
of facile methods for catalyst separation and recycling [5] and even more introducing
alternative solvents as a replacement of conventional, usually toxic and volatile
organic media. The latter is crucial to achieve environmentally benign alternatives for
hydroformylation reactions. The aqueous [6] and fluorous [7] biphasic systems as
well as the application of supercritical carbon-dioxide [8] and room temperature ionic
liquids [9] have been successfully applied for this purposes. Very recently, as a result
of the intensive research activity on biomass conversion, a sustainable liquid, γ-
valerolactone (GVL) was identified as a renewable platform molecule [10]. It can be
used for the production of alkanes and alkenes [11], transportation fuels [12], polymer
compounds [13], lighter fluid [14], as well as a surrogate of conventional organic
solvents for synthesis and catalysis. Beyond its first application as a solvent for
dehydration of carbohydrates [15,16], several important transition metal catalyzed
reactions such as Heck [17] Sonogashira [18] and Hiyama cross-coupling reactions
[ 19 ], Catellani-reaction [ 20 ], platinum-catalyzed hydroformylation [ 21 ] and
palladium-catalyzed aminocarbonylation [22] were successfully performed in GVL
without significant changes in the catalytic systems' efficiency. On the other hand,
GVL can be produced from carbohydrate rich biomass or biomass-based wastes via
levulinic acid [23, 24] making it fossil independent alternative reaction media. GVL
2

ACCEPTED MANUSCRIPT
84
85
86
87
88
89
90
91
92
occurs naturally in fruits and fermented products such as wines and beers [25],
accordingly it can be considered as a non-toxic substance. It should be noted that
moisture content of GVL could be crucial as follows i) water content could have a
serious influence on the operation of transition metal-based catalyst ii) the ring
opening of GVL results in the formation of 4-hydroxyvaleric acid [26], which could
lead to unwanted side reactions. The investigation of phase behaviour of GVL and
water revealed that water can be completely separated by vacuum distillation without
formation of azeotropic mixture in whole concentration range [30] overcoming this
issue.
93
Herein we report, the investigation of hydroformylation of styrene as well as
functionalized olefins such as α-methylstyrene, dimethyl itaconate, and limonene in
the presence of in situ generated rhodium-chiral diphosphine catalyst in GVL. The
activity, as well as chemo-, regio- and enantioselectivities of the aforementioned
systems, obtained in toluene as conventional and GVL as non-toxic, biomass-based
solvent, are compared.
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
2. Experimental
General procedures
Toluene, gamma-valerolactone, styrene, α-methylstyrene, dimethyl itaconate, and
(R)-limonene and bidentate phosphine ligands were obtained from Sigma-Aldrich Kft.
Budapest, Hungary. The [Rh(nbd)Cl]2 precursor was synthesized using standard
procedure [27]. Toluene was distilled and purified by standard methods and stored
under argon. Substrates and ligands were used as obtained without any further
purification. All reactions were carried out under argon atmosphere using standard
Schlenk technique. Gamma-valerolactone was purified by vacuum distillation (2 Torr,
80–82 °C) and stored under nitrogen. The GC and chiral GC measurements were run
on a Chrom-Card Trace GC-Focus GC gas-chromatograph. The enantiomeric
excesses were determined on a capillary Cyclodex-column.
Hydroformylation experiments
In a typical hydroformylation experiment, a solution of [Rh(nbd)Cl]2 (2.3 mg,
0.005 mmol), corresponding diphosphine (0.01 mmol) in 5 mL of toluene containing
0.115 mL (1.0 mmol) of styrene was transferred under argon into a 100 mL stainless
steel autoclave. The reaction mixture was pressurized to 80 bar total pressure (CO:H2
= 1:1) and placed in an oil bath of appropriate temperature and the mixture was stirred
with an internal magnetic stirrer. Sample was taken from the mixture and the pressure
was monitored throughout the reaction. After cooling and venting of the autoclave,
the pale yellow solution was removed and immediately analysed by GC and chiral
GC. For appropriate determination of enantiomeric excess, 10 mL of hexane was
added to a sample of the reaction mixture (2 mL) and washed with water (twice 10
mL). The hexane phase was dried over Na2SO4, filtered and concentrated to a
colorless oil. The CH2Cl2 solution of this GVL-free sample was applied for chiral GC.
3

ACCEPTED MANUSCRIPT
127
128
129
130
131
132
133
134
135
136
137
138
139
140
3. Results and Discussion
The replacement of conventional organic solvents by environmentally benign
alternative could result in a safer alternative of hydroformylation. In comparison to
GVL, the temperature dependence of the vapor pressure of solvents that are generally
utilized for hydroformylation, it can be stated that the replacement of these media
with GVL could result in an environmentally benign catalytic system. The vapor
pressures of GVL in the temperature range of hydroformylation reactions are two
orders of magnitude less than hexane, benzene or toluene, just to name a few (Figure
1).
141
142
143
Figure 1 Vapor pressures of commonly used solvents for hydroformylation and GVL. Data were
obtained as follows: toluene, hexane, octane ref. 28, benzene ref 29; GVL ref. 30.
144
145
146
147
148
149
150
151
152
153
154
Although the platinum-chiral diphosphine-tin(II) chloride systems were successfully
utilized in enantioselective hydroformylation, the rhodium-containing systems have
shown the best performance due to their high activity and, since the discovery of
Takaya's rhodium-BINAPHOS catalysts [31], due to excellent enantioselectivity as
well. In order to demonstrate the applicability of GVL as a reaction medium for Rh-
catalyzed hydroformylation of functionalized olefins, we initially investigated the
conversion of styrene (A) as a model substrate (Scheme 1) in the presence of catalyst
in situ formed from [Rh(nbd)Cl]2 and chiral bidentate phosphine ligands (Figure 2).
CHO
[Rh(nbd)Cl]2
/
CHO
P
P
+ CO + H2
+
+
GVL
(A)
(B)
(C)
(D)
155
156
Scheme 1 Hydroformylation of styrene (A) in GVL
157
158
4

ACCEPTED MANUSCRIPT
Ph
Ph
P
Ph
P
P
3
Ph
N
P
TPP
Ph
Ph
Ph
P
P
Ph
Ph
Ph
Ph
Ph
P
P
(S,S)-BDPP
(R)-BINAP
(R)-QUINAP
Ph
Ph
DPPP
Ph
O
Ph
O
Ph
P
P
O
O
O
Ph
Ph
P
P
Ph
O
O
P
Fe
P
Ph
P
O
P
Ph
CH3
O
Ph
Ph
O
(Rc),(Sp)-JOSIPHOS
(R,R)-DIOP
(S)-SEGPHOS
(S)-(DM)-SEGPHOS
159
160
161
Figure 2 Ligands used in this work
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
Initially, hydroformylation of styrene (Scheme 1) was performed in the presence of
catalyst in situ formed from [Rh(nbd)Cl]2 and achiral phosphines in GVL. When 6
eqv. of PPh3 (i.e. Rh:PPh3 = 1:3) was used, no significant difference in both
conversion and chemoselectivity was observed. Chemoselectivity towards aldehydes
were > 98.5% for both solvents. By the use of 2 eqv. of DPPP ligand i.e. Rh:Ligand =
1:1, slower reaction was detected in GVL than in toluene. However, the nearly
chemospecific reaction is accompanied by the slight decrease of the regioselectivity
i.e. more linear aldehyde was formed in GVL than in toluene (Table 1, entries 1-3).
This is in accordance with our recent observation for Pt-catalyzed hydroformylation
of styrene [21].
Subsequently, several diphosphines (mainly chiral enantiomerically pure
diphosphines) were also tested in asymmetric hydroformylation of styrene in
rhodium-catalyzed reaction. Carrying out the reaction in the presence of Rh-BDPP
system (Table 1, entries 6-17) the following statements can be made:
i) The activity of the rhodium-BDPP system (and that of the rhodium-DPPP
system) in GVL is lower than in toluene (compare for instance entries 9 and 18, and
entries 4 and 5, respectively). However, as expected, lower conversions were obtained
o
at low pressure (15/15 bar) (entry 13) and low temperature (25 C) (entry 10). It
should be noted that GVL as a non-protic dipolar species could act as a coordinating
solvent reducing the reaction rate. Similar observations were reported for
tetrahydrofurane [ 32 , 33 ]. When Rh(CO)2(acac) was used as a precursor no
significant changes in the activity and selectivity were observed (entries 7 and 8).
ii) The high chemoselectivities towards aldehydes obtained in toluene (ca.
99%, entries 16-18) was further increased in GVL. In general, aldehyde selectivity
higher than 99.8% can be achieved. The only lower chemoselectivity was obtained at
high hydrogen partial pressure obtained by the variation of the reaction conditions
(Table 1, entry 14).
iii) The experiments carried out at variable temperatures have shown no
significant dependence of chemoselectivity on the reaction temperature (entries 6-10).
5

ACCEPTED MANUSCRIPT
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
It should be noted that in toluene the lowering of the temperature resulted in a slight
increase of the chemoselectivity. As one of the important advantages of using GVL,
as it has been revealed by detailed GC-MS investigations, the practically
chemoselective reaction towards aldehydes in GVL has to be mentioned.
iv) As for the regioselectivity, nearly the same regioselectivities were obtained
in toluene and GVL (Table 1, entries 16-18 and 6-9, respectively). Some decrease
(less than 2%) in regioselectivity towards branched aldehyde can only be observed
when the reaction was carried out at low temperatures.
v) The reactions carried out at various pressures have shown no strong
dependence of regioselectivity data on the partial pressure of carbon monoxide or
hydrogen (Table 1, entries 13-15).
vi) The enantioselectivities obtained in the presence of BDPP in GVL, similar
to those obtained in toluene, are very low in general. The ee of the hydroformylation
towards branched aldehyde (2-phenylpropanal) could be increased to 9% when higher
BDPP/Rh (3/1) ratios were used (entries 12, 13).
Regarding the other diphosphines, such as BINAP, DIOP, JOSIPHOS and
QUINAP (Table 1, entries 19-38) very similar results obtained in GVL can be
mentioned. That is, the reaction is practically chemospecific regarding aldehydes,
provides high regioselectivity towards branched aldehyde (2-phenylpropanal) at low
temperature and can provide low enantioselectivities under various conditions. It is
worth mentioning that a surprisingly high dependence of regioselectivity on the
temperature was observed with BINAP in GVL (Table 1, entries 19-24). When
SEGPHOS and DM-SEGPHOS ligands with a smaller dihedral angle were used,
significantly lower activity and negligible enantioselectivities were detected in GVL
(Table 1, entries 36-38).
Additionally, efforts were made to separate and re-use the catalyst. By
applying Rh/BDPP system under condition given in Table 1 entry 11, the products as
a GVL solution can be separated by vacuum (10 mmHg) distillation at 80–85 °C. The
glue-like residue that remained at the bottom of distillation flask, was re-dissolved in
in GVL and re-used in consecutive cycle under identical conditions. We demonstrated
o
that the Rh-BDPP system could be recycled for 3 times at 60 C and 80 bar pressure
(CO:H2 = 1:1). While a perfect chemoselectivity towards aldehydes (>99.9%) was
maintained throughout this procedure, some decrease in both conversion and
regioselectivity was observed reflecting the partial degradation of the catalyst (Table
2.). Similar observation was reported for Pt-BINAP-tin(II)chloride system [21].
6

ACCEPTED MANUSCRIPT
229
230
Table 1. Hydroformylation of styrene in GVL (and, for comparison in toluene) in the
presence of Rh-phosphine in situ systems a)
b
c
Entry
Ligand
Solvent
T
(°C)
p(CO)/p(H2) Time
Conv.
(%)
Rc
Rbr
ee.d
(%)
(bar)
40/40
40/40
40/40
40/40
40/40
40/40
40/40
40/40
40/40
40/40
15/15
40/40
15/15
20/80
40/60
40/40
40/40
40/40
40/40
40/40
40/40
40/40
40/40
40/40
40/40
40/40
20/20
20/20
20/20
20/20
20/20
20/20
(h)
24
1
(%)
99.5
90.6
98.8
99.5
98.7
99.9
99.8
99.6
99.2
99.8
99.8
>99
(%)
67
93
87
83
89
90
92
92
1e
2e
3e
PPh3
PPh3
GVL
toluene
toluene
GVL
100
100
100
80
80
80
60
60
40
25
60
60
60
60
60
80
60
40
100
80
80
40
60
80
80
80
60
40
40
60
60
60
100
10
-
-
PPh3
24
24
1
100
100
87
-
-
4
DPPP
5
DPPP
Toluene
GVL
-
6
BDPP
24
24
24
20
68
24
24
24
24
24
1
100
63
7 (S)
3 (S)
2 (S)
7
BDPP
GVL
8f
9
BDPP
BDPP
GVL
GVL
57
5
93.9 10 (S)
10
11
12e
13e
14
15
16
17
18
19
20
21f
22
23f
24
25
26
27
28
29
30
31
32
BDPP
GVL
51
98
>99
95.3
92.3
94
0
BDPP
GVL
76
0
BDPP
GVL
>99
79
9 (S)
9 (S)
2 (R)
2 (R)
4 (R)
2 (R)
7 (S)
0
BDPP
GVL
99.9
95.8
>99.9
98.8
98.9
99.2
99.6
99.5
99.7
>99.9
99.7
98.4
99.9
99
BDPP
GVL
100
100
100
86
BDPP
GVL
93
BDPP
toluene
toluene
toluene
GVL
89
BDPP
5
94
BDPP
24
3
100
55
95
BINAP
BINAP
BINAP
BINAP
BINAP
BINAP
JOSIPHOS
JOSIPHOS
DIOP
66
GVL
3
86
77
1 (S)
1 (S)
5 (R)
2 (S)
4 (R)
4 (S)
2 (S)
2 (S)
n.d.
GVL
3
51
88
GVL
45
24
1
68
95
GVL
87
91
toluene
GVL
99
91
4
92
87
toluene
GVL
3
100
99.8
18
92
24
4.5
24
24
30
30
>99.9 99.4
>99.9 98.3
>99.9 98.3
DIOP
GVL
DIOP
GVL
28.6
>99
6.9
99.9
2 (S)
1 (S)
DIOP
toluene
GVL
99.9
99.1
99.4
90.1
QUINAP
QUINAP
81.4 10 (S)
toluene
79.3
2 (R)
33
34
35
SEGPHOS
SEGPHOS
SEGPHOS
GVL
GVL
60
60
60
40/40
40/40
40/40
5
21
81
61
90
99
98
91
93
n.d.
1 (S)
5 (S)
24
24
toluene
>99
36
37
38
DM-SEGPHOS
DM-SEGPHOS
DM-SEGPHOS
GVL
GVL
60
60
60
40/40
40/40
40/40
5
14
27
11
63
97
97
93
94
n.d.
3 (S)
4 (S)
24
24
toluene
>99
231
232
233
234
235
236
237
238
239
B: 2-phenylpropanal, C: 3-phenylpropanal, D: ethylbenzene.
a
Reaction conditions (unless otherwise stated): Catalyst precursor: [Rh(nbd)Cl]2, Rh/Ligand/styrene = 1/1/100, 1
mmol of styrene, solvent: 5 mL of toluene (or GVL).
b Chemoselectivity towards aldehydes (B, C). [(moles of B + moles of C)/(moles of B + moles of C + moles of D)
× 100].
c Regioselectivity towards branched aldehyde (B). [moles of B/(moles of B + moles of C) × 100].
d Enantioselectivities were determined by chiral GC. (S)-2-phenylpropanal was eluted before the (R) enantiomer.
e Rh:Ligand = 1:3
f Rh(CO)2(acac) was used as a precursor.
7

ACCEPTED MANUSCRIPT
240
241
Table 2. Re-use of Rh-BDPP catalyst in the hydroformylation of styrene at 60 °C a)
Cycle
Conversion (%)
Rc
Rbr
1
2
3
4
>99
>99
95
>99
>99
>99
>99
95.3
94.0
92.0
90.0
66
242
243
a) Reaction conditions: Catalyst precursor: [Rh(nbd)Cl]2, Rh/Ligand/styrene = 1/1/100, 1 mmol of
styrene, in 5 mL of GVL.
244
245
246
247
248
249
250
251
252
Two further substrates, α-methylstyrene (E) and dimethyl itaconate (I) were
also subjected to hydroformylation.
The application of GVL in the hydroformylation of α-methylstyrene (Scheme
2) resulted in lower activity related to those obtained in toluene; however, resulted in
higher chemoselectivity towards aldehydes while the extremely high regioselectivity
towards the chiral aldehyde (G) was maintained. This is true for both BDPP- and
BINAP-containing systems (Table 3, entries 1,3 and 2,4, respectively).
[Rh(nbd)Cl]2 /
CHO
CHO
P
P
+ CO + H2
+
+
GVL
(E)
(F)
(G)
(H)
253
254
Scheme 2 Hydroformylation of α-methylstyrene (E)
255
256
257
258
259
260
261
262
In contrary to styrene-type substrates, the hydroformylation of dimethyl
itaconate (I) (Scheme 3) resulted in higher conversion in GVL. The difference in
activity was surprisingly high at low temperature (Table 3, entries 5 and 6). However,
low chemoselectivity towards aldehydes (J, K) were observed in general. That is,
practically only hydrogenation takes place at high temperature in GVL both in the
presence of BDPP and DIOP ligands (Table 3, entries 8 and 10).
O
O
O
O
[Rh(nbd)Cl]2 /
BDPP or DIOP
OHC
OHC
O
O
O
O
O
O
*
*
O
O
*
+
+
+ CO + H2
GVL
O
O
O
O
(I)
(J)
(K)
(L)
263
264
Scheme 3 Hydroformylation of dimethyl itaconate (I)
265
266
267
268
269
270
271
8

ACCEPTED MANUSCRIPT
272
273
Table 3. Hydroformylation of various substrates in GVL (and, for comparison in toluene) in
the presence of Rh-phosphine 'in situ' systems a)
b
c
Entry
Substrate
Ligand
Solvent
T
(°C)
Time
(h)
Conv.
(%)
Rc
Rlin
ee. (J)d ee. (G/K)d ee. (L)d
(%)
(%)
>99
>99
>99
>99
27
(%)
(%)
(%)
1
2
3
4
5
6
7
8
9
BDPP
BINAP
BDPP
BINAP
BDPP
BDPP
BDPP
BDPP
DIOP
GVL
GVL
60
60
24
24
24
24
24
24
24
24
20
20
9.2
3.6
44.6
23.1
8
95
-
0
-
α-methylstyrene
α-methylstyrene
α-methylstyrene
α-methylstyrene
dimethyl itaconate
dimethyl itaconate
dimethyl itaconate
dimethyl itaconate
dimethyl itaconate
>99
77
-
-
0
-
toluene
toluene
toluene
GVL
60
0
-
60
>99
40
-
0
-
60
3.6 (-)
0
0
0.2 (R)
0.2 (R)
0.3 (S)
0.3 (R)
0
60
47
9
1
n.d.
0.5 (S)
n.d.
1.2 (S)
n.d.
toluene
GVL
100
100
100
100
>99
>99
73
15
64
2.2 (-)
n.d.
0.8 (-)
n.d.
<1
25
n.d.
22
toluene
GVL
10 dimethyl itaconate
DIOP
>99
<1
n.d.
1.8 (R)
274
275
276
277
278
279
280
281
282
F: 2-methyl-2-phenylpropanal (or J: dimethyl 2-formyl-2-methylsuccinate) (branched aldehyde)
G: 3-phenylbutanal (or K: dimethyl 2-(formylmethyl)succinate) (linear/less branched aldehyde)
H: isopropylbenzene (or L: dimethyl 2-methylsuccinate) (hydrogenated product)
a Reaction conditions: Rh/Ligand/substrate = 1/1/100, 1 mmol of substrate, p(CO)=p(H2)= 40 bar; solvent: 5 mL
GVL (or toluene).
b Chemoselectivity towards aldehydes (F/G, J/K). [(moles of F/J + moles of G/K)/(moles of F/J + moles of G/K
+ moles of H/L) × 100].
c Regioselectivity towards linear aldehyde (G/K). [moles of G/K/(moles of G/K + moles of F/J) × 100].
d Enantioselectivities were determined by chiral GC.
283
284
285
286
287
288
289
290
291
292
293
A
terpene derivative, (R)-limonene of practical importance was
hydroformylated under similar conditions (Scheme 4). As observed before in
platinum-catalyzed hydroformylation 34 and palladium-catalyzed
[
]
hydroalkoxycarbonylation [35], high regioselectivity towards linear regioisomer (O)
was obtained also in rhodium-catalyzed hydroformylation in GVL. The
chemoselectivity towards aldehydes (N, O) is about 75%, i.e., some hydrogenated
product (P) was always present in the reaction mixture. The two diastereoisomers
were formed in close to 1/1 ratio. A slight diastereoselection of 16% and 4% was
observed with BDPP- and BINAP-containing catalysts, respectively.
[Rh(nbd)Cl]2 /
P
P
+
+
+ CO + H2
*
GVL
*
*
*
CHO
CHO
*
(M)
(N)
(O)
(P)
294
295
Scheme 4 Hydroformylation of (R)-limonene (M)
296
297
298
Table 4. Hydroformylation of (R)-limonene in GVL in the presence of Rh-phosphine 'in situ'
systemsa)
c
Entry
Substrate
Ligand
Solvent
T
Time Conv.
Rcb
Rlin de. (O)d
(°C)
(h)
20
20
(%)
>99
>99
(%)
(%)
(%)
16
4
1
2
(R)-Limonene
(R)-Limonene
BDPP
GVL
GVL
100
100
75
77
95
BINAP
96
299
aReaction conditions: Rh/Ligand/substrate = 1/1/100, 1 mmol of substrate, p(CO) = p(H2) = 40 bar; solvent: 5 mL
9

ACCEPTED MANUSCRIPT
300
301
302
303
304
bChemoselectivity towards aldehydes (N, O). [(moles of N +moles of O)/(moles of N + moles of O + moles of P)
× 100].
cRegioselectivity towards selected aldehyde (O). [moles of O/(moles of O + moles of N) × 100].
dDiastereomeric excess. [(moles of diastereomer 1-moles of diastereomer 2)/(moles of diastereomer 1 + moles of
diastereomer 2) × 100
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
3. Conclusion
In summary, the application of gamma-valerolactone as a renewable and
environmental friendly solvent was successfully utilized for bidentate phosphine
ligand-modified rhodium-catalyzed hydroformylation of styrene, α-methylstyrene,
dimethyl itaconate, and (R)-limonene. Although, the catalytic activities were lower in
GVL compared to toluene as a conventional organic solvent for hydroformylation,
remarkable chemo- and regioselectivities were observed in GVL. Results proved that
GVL is a good biomass-based alternative solvent and could be very promising for its
application in both industrial and academic processes.
Acknowledgment
This work was supported by the GINOP-2.3.2-15-2016-00049 grant and
National Research, Development and Innovation Office – NKFIH (PD 116559 and
K113177). L. T. Mika is grateful the support of Bolyai János Research Scholarship of
the Hungarian Academy of Sciences.
References
[1] B. Cornils, W.A. Herrmann, M. Rasch, Otto Roelen, Pioneer in Industrial
Homogeneous Catalysis, Angew. Chem. Int. Ed. Engl. 33 (1994) 2144–2163.
[2] L.T. Mika, F. Ungváry, Hydroformylation – Homogeneous, in: I. T. Horváth
(Ed.), Encyclopedia of Catalysis, 2011, doi:10.1002/0471227617.eoc108.pub2
[3] C. Kohlpainter, Hydroformylation – Industrial, in: I. T. Horváth (Ed.),
Encyclopedia of Catalysis, John-Wiley and Sons, , New York, 2003, pp. 787–
808.
[4] B. Breit, Synthetic Aspects of Stereoselective Hydroformylation, Acc. Chem.
Res. 36 (2003) 264–275.
[5] D.J. Cole-Hamilton, Homogeneous catalysis--new approaches to catalyst
separation, recovery, and recycling, Science. 299 (2003) 1702–1706.
[6] B. Cornils, E. Wiebus, Aqueous catalysts for organic reactions CHEMTECH 25
(1995) 33-38.
[7] I.T. Horváth, J. Rábai, Facile Catalyst Separation Without Water: Fluorous
Biphase Hydroformylation of Olefins, Science. 266 (1994) 72–75.
10

ACCEPTED MANUSCRIPT
[8] W. Leitner, Supercritical Carbon Dioxide as a Green Reaction Medium for
Catalysis, Acc. Chem. Res. 35 (2002) 746–756.
[9] J.P. Hallett, T. Welton, Room-Temperature Ionic Liquids: Solvents for
Synthesis and Catalysis. 2, Chem. Rev. 111 (2011) 3508–3576.
[10] I.T. Horváth, H. Mehdi, V. Fábos, L. Boda, L.T. Mika, γ-Valerolactone—a
sustainable liquid for energy and carbon-based chemicals, Green Chem. 10
(2008) 238–242.
[11] H. Mehdi, V. Fábos, R. Tuba, A. Bodor, L.T. Mika, I.T. Horváth, Integration of
Homogeneous and Heterogeneous Catalytic Processes for a Multi-step
Conversion of Biomass: From Sucrose to Levulinic Acid, γ-Valerolactone, 1,4-
Pentanediol, 2-Methyl-tetrahydrofuran, and Alkanes, Top Catal. 48 (2008) 49–
54.
[12] J.Q. Bond, D.M. Alonso, D. Wang, R.M. West, Integrated catalytic conversion
of γ-valerolactone to liquid alkenes for transportation fuels, Science. 327 (2010)
1110–1114.
[13] M. Chalid, H.J. Heeres, A.A. Broekhuis, Ring-opening of γ-valerolactone with
amino compounds, J. Appl. Polym. Sci. 123 (2011) 3556–3564.
[14] V. Fábos, M.Y. Lui, Y.F. Mui, Y.Y. Wong, L.T. Mika, L. Qi, et al., Use of
Gamma-Valerolactone as an Illuminating Liquid and Lighter Fluid, ACS
Sustainable Chem. Eng. 3 (2015) 1899–1904.
[15] L. Qi, I.T. Horváth, Catalytic Conversion of Fructose to γ-Valerolactone in γ-
Valerolactone, ACS Catal. 2 (2012) 2247–2249.
[16] L. Qi, Y.F. Mui, S.W. Lo, M.Y. Lui, G.R. Akien, I.T. Horváth, Catalytic
Conversion of Fructose, Glucose, and Sucrose to 5-(Hydroxymethyl)furfural
and Levulinic and Formic Acids in γ-Valerolactone As a Green Solvent, ACS
Catal. 4 (2014) 1470–1477.
[17] G. Strappaveccia, E. Ismalaj, C. Petrucci, D. Lanari, A. Marrocchi, M. Drees, et
al., A biomass-derived safe medium to replace toxic dipolar solvents and access
cleaner Heck coupling reactions, Green Chem. 17 (2015) 365–372.
[18] G. Strappaveccia, L. Luciani, E. Bartollini, A. Marrocchi, F. Pizzo, L. Vaccaro,
γ-Valerolactone as an alternative biomass-derived medium for the Sonogashira
reaction, Green Chem. 17 (2015) 1071–1076.
[19] E. Ismalaj, G. Strappaveccia, E. Ballerini, F. Elisei, O. Piermatti, D. Gelman, et
al., γ-Valerolactone as a Renewable Dipolar Aprotic Solvent Deriving from
Biomass Degradation for the Hiyama Reaction, ACS Sustainable Chem. Eng. 2
(2014) 2461–2464.
[20] D. Rasina, A. Kahler-Quesada, S. Ziarelli, S. Warratz, H. Cao, S. Santoro, et al.,
Heterogeneous palladium-catalysed Catellani reaction in biomass-derived γ-
valerolactone, Green Chem. 18 (2016) 5025–5030.
[21] P. Pongrácz, L. Kollár, L.T. Mika, A step towards hydroformylation under
sustainable conditions: platinum-catalysed enantioselective hydroformylation of
styrene in gamma-valerolactone, Green Chem. 18 (2016) 842–847.
11

ACCEPTED MANUSCRIPT
[22] D. Marosvölgyi-Haskó, B. Lengyel, J.M. Tukacs, L. Kollár, L.T. Mika,
Application of γ-Valerolactone as an Alternative Biomass-Based Medium for
Aminocarbonylation Reactions, ChemPlusChem. 81 (2016) 1224–1229.
[23] L.T. Mika, E. Cséfalvay, I.T. Horváth, The role of water in catalytic biomass-
based technologies to produce chemicals and fuels, Catal. Today. 247 (2015)
33–46.
[24] J.M. Tukacs, A.T. Holló, R. Rétfalvi, E. Cséfalvay, G. Dibó, D. Havasi, L.T.
Mika, Microwave-Assisted Valorization of Biowastes to Levulinic
Acid, ChemistrySelect, 2 (2017) 1375-1380.
[25] P. M. Izquerdo-Canas, A. Mena-Morales, E. García-Romero, Malolactic
fermentation before or during wine aging in barrels LWT Food Sci. Technol.,
66 (2016) 468-474.
[26] C.Y.Y. Wong, A.W-T. Choi, M. Lui, B. Fridrich, A.K. Horváth, L.T. Mika, I.T.
Horváth, Stability of Gamma-valerolactone under Neutral, Acidic, and Basic
Conditions, Struct. Chem. 28 (2017) 423-429.
[27] Abel, E. W.; Bennett, M. A.; Wilkinson, G. Norbornadiene-metal complexes
and some related compounds. J. Chem. Soc. (1959) 3178-3182.
[28] C.B. Willingham, W.J. Taylor, J.M. Pignocco, F.D. Rossini, Vapor Pressures
and Boiling Points of Some Paraffin, Alkylcyclopentane, Alkylcyclohexane,
and Alkylbenzene Hydrocarbons, J. Res. Natl. Bur. Stand. 35 (1945) 219 – 244.
[29] C. Eon, C. Pommier, G. Guiochon, Vapor pressures and second virial
coefficients of some five-membered heterocyclic derivatives, J. Chem. Eng.
Data 16 (1971) 408-410.
[30] D. Havasi, P. Mizsey, L.T. Mika, Vapor-Liquid Equilibrium Study of the
Gamma-Valerolactone-Water Binary System, J. Chem. Eng. Data. 61 (2016)
1502-1508.
[31] N. Sakai, S. Mano, K. Nozaki, H. Takaya, Highly enantioselective
hydroformylation of olefins catalyzed by new phosphinephosphite-Rh(I)
complexes. J. Am. Chem. Soc. 115 (1993) 7033-7034.
[32] N. Sakai, K. Nozaki, K. Mashima, H. Takaya, Asymmetric hydroformylation of
vinyl acetate by use of chiral bis(triarylphosphite)-rhodium(I) complexes.
Tetrahedron: Asymm., 3 (1992) 583–586.
[33] T. V. RajanBabu, T. A. Ayers, Electronic effects in asymmetric catalysis:
Hydroformylation of olefins. Tetrahedron Lett. 35 (1994) 4295–4298.
[34] L. Kollár, J. Bakos, B. Heil, P. Sándor, G. Szalontai, Hydroformylation of
Chiral Terpenes with PtCl(SnCl )(bisphosphine) as Catalyst. J. Organomet.
3
Chem. 385 (1990) 147-152.
[35] R. Nagel, T. Chenal, I. Ciprès, P. Kalck, J.-C, Daran, J. Vaissermann, Carbon
monoxide as a building block in organic synthesis. Part V. Involvement of
palladium-hydride species in carbonylation reactions of monoterpenes – X-ray
crystal-structure of [Ph3PCH2CH=CHPh]4[PdCl6][SnCl6]. J. Organomet. Chem.
480 (1994) 91-102.
12

ACCEPTED MANUSCRIPT
Rhodium-catalyzed hydroformylation in γ-valerolactone as a biomass-
derived solvent
Péter Pongrácz,b Brigitta Bartalb, László Kollár,b and László T. Mika,a,*
aDepartment of Chemical and Environmental Process Engineering, Budapest University of Technology
and Economics, Műegyetem rkp. 3., H-1111, Budapest, Hungary.
bDepartment of Inorganic Chemistry, University of Pécs and János Szentágothai Research Center and
MTA-PTE Research Group for Selective Chemical Syntheses,
Ifjúság u. 6., H-7624, Pécs, Hungary.
Highlights
•
•
•
γ-valerolactone was applied as a solvent for Rh-catalyzed hydroformylation.
Results were compared to toluene as a FDA Class 2 solvent.
Remarkable chemo- and regioselectivities were achived in GVL.