Angewandte
Chemie
Table 1: Hydrogenation of phenylacetic acid by H2 in the presence of
Table 2: A general catalytic hydrogenation of carboxylic acids.[a,b]
triphos.[a]
Entry Catalyst
Additive 1 Additive 2 Yield[b] Yield[b]
2a [%] 3a [%]
1
2
3
4
5
6
7
8
Ru(acac)3
Ru(acac)3
Ru(acac)3
Ru(acac)3
Ru(acac)3
Ru(acac)3
Ru(acac)3
[Ru(triphos)(CO)H2] Sn(OTf)2
[Ru(p-cymene)Cl2]2 Sn(OTf)2
Ru[CH3S(O)CH3]4Cl2 Sn(OTf)2
–
H2O
H2O
–
4
0
0
19
7
4
49
10
0
0
0
0
Sn(OTf)2
Sn(OTf)2
Me2SnCl
Me2SnO
Bu3SnO
Sn(OTf)2
0[c]
26
6
14
9
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
20
10[c]
8[c]
7[c]
11[c]
2[d]
9
10
11
12
Ru(PPh3)3Cl2
Ru(acac)3
Sn(OTf)2
Sn(OTf)2
95
[a] Reaction conditions: 0.5 mmol substrate, catalyst (4 mol%), ligand
(5 mol%), additive 1 (10 mol%), 2 mL toluene, 0.5 mL H2O, 60 bar H2,
reaction temperature (1608C), 24 h. [b] GC yields. [c] Ligand-free.
[d] 48 h.
nium complexes in the hydrogenation of phenylacetic acid to
2-phenylethan-1-ol under the previously optimized condi-
tions. Among the tested complexes only [Ru(triphos)(CO)H2]
also catalyzed this hydrogenation producing 2a in 10% yield.
This demonstrates the importance of the triphos ligand.
Then, the most active catalyst system, Ru(acac)3/triphos/
Sn(OTf)2, was used to examine the scope and limitations of
this methodology. As shown in Table 2, the reduction of
a broad range of aliphatic and aromatic carboxylic acids
proceeded well. In case of phenyl acetic acids, sterically more
hindered substrates and electron-donating groups showed
slightly lower reactivity (Table 2, 2d–2g). However, increas-
ing the reaction temperature led to good yields, too.
Interestingly, perfluorophenyl acetic acid is transformed into
the corresponding alcohol in 67% yield (Table 2, 2j).
Diphenylacetic acid and naphthylacetic acid were also
successfully converted to the respective alcohols in excellent
yields (Table 2, 2k and 2l). Moreover, hydrogenations of
cyclic aliphatic carboxylic acids proceeded smoothly to the
desired alcohols in 69–83% yields (Table 2, 2n–2p). Similarly,
2-propylpentanol is obtained in 79% yield by hydrogenation
of 2-propylpentanoic acid (Table 2, 2q).
Notably, no catalytic hydrogenation occurred for benzoic
acid under the previously optimized conditions. Nevertheless,
small amounts of benzyl alcohol is formed using Al(OTf)3
instead of Sn(OTf)2 as the co-catalyst, albeit with dibenzyl
ether as the main product. Gratifyingly, hydrogenation of
benzoic acid led to benzyl alcohol in 42% yield using
10 mol% Al(OTf)3 in the presence of H2O and CH3OH at
1608C (Table 2, 2r). Furthermore, 2,4,6-trichlorobenzoic acid
and 2,3,4,5,6-pentafluorobenzoic acid gave the corresponding
alcohols in 70% and 67% yields, respectively, using Ru-
(acac)3/triphos/Al(OTf)3 (Table 2, 2s and 2t).
[a] Reaction conditions: 0.5 mmol substrate, Ru(acac)3 (4 mol%),
triphos (5 mol%), Sn(OTf)2 (10 mol%), 2 mL toluene, 0.5 mL H2O,
60 bar H2, 1608C (reaction temperature), 48 h. [b] Isolated yields.
[c] 1658C. [d] GC yields. [e] Reaction conditions: 0.5 mmol substrate,
Ru(acac)3 (4 mol%), triphos (5 mol%), Al(OTf)3 (10 mol%), 2 mL
toluene, 0.1 mL H2O, 0.3 mL methanol, 60 bar H2, 1608C (reaction
temperature), 24 h.
chemical treatment of biomass,[15] is an important process and
offers new opportunities.[16] For example, fatty alcohols, which
are widely used in the production of surfactants, polymers and
solvents, can be easily accessed from the corresponding acids.
Thus, we examined the reactivity of different bio-relevant
carboxylic acids (Table 3). Indeed, the novel Ru(acac)3/
triphos/Sn(OTf)2 catalyst system showed good activity for
the hydrogenation of 9 renewable carboxylic acids to the
corresponding alcohols. More specifically, the reduction of
low and medium chain aliphatic acids such as propionic,
butyric, hexanoic and octanoic generated the desired products
in 63–79% yields under the optimized conditions (Table 3,
2aa–2ad). For the longer-chain acids the yields of the
products decreased with increasing length of the alkyl chain,
which may be caused by the insufficient solubility in toluene.
However, dodecan-1-ol, hexadecan-1-ol and octadecan-1-ol
are obtained in preparative useful yields (69–84%) by
increasing the reaction temperature to 1658C (Table 3, 2ae–
2ag). Moreover, the catalytic transformation of succinic acid
to the desired diol was realized (Table 3, 2ah). Finally,
tetrahydro-2-furoic acid, which is a useful intermediate and
is used for the preparation of several drugs, gave tetrahy-
drofurfuryl alcohol[17] in 80% yield (Table 3, 2ai).
In the context of biorefinery, the selective hydrogenation
of carboxylic acids, which are easily obtained by biological or
To investigate the reaction mechanism, a time–concen-
tration profile of the model hydrogenation under the
Angew. Chem. Int. Ed. 2015, 54, 10596 –10599
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim