DOI: 10.1002/chem.201101478
Straightforward Uranium-Catalyzed Dehydration of Primary Amides to
Nitriles
Stephan Enthaler*[a]
During the last few years the coordination chemistry of
uranium has been rediscovered and numeral exciting coordi-
nation motifs have been approached.[1] Based on the report-
ed achievements and the intrinsic abilities of uranium, fasci-
nating purposes have been proposed for the future, includ-
ing material science and catalysis.[2] However, even if several
hundred well-defined uranium complexes are accessible, the
application in homogeneous catalysis has been so far scarce-
ly reported, for example, hydroaminations, hydrosilylations,
polymerization, and reductions.[3] Besides, several uranium
precursors are available as industrial side products on a
large scale. Hence, studies to investigate the potential of
uranium and therefore convert a waste product to a valuable
catalyst will be highly desired.[2a] On the other hand, from
the organic chemistry point of view, compounds containing
nitrile functionalities are broadly applied in organic chemis-
try and are fundamental building blocks in industry to
access pharmaceuticals, agrochemicals, and polymers.[4]
Among the diverse techniques to produce nitriles, one suita-
ble and traditional access is the dehydration of primary
amides. In particular, the dehydration of primary amides in
the presence of catalytic amounts of metal precursors (e.g.,
Ru, Pd, Rh, W, V, Fe) can be a proficient choice.[5–14] How-
ever, established methods based on transition-metals require
harsh reaction conditions, high catalyst loadings, or the addi-
hydration reagent, which is an excellent trimethylsilyl-trans-
fer compound.[15]
Initially, the dehydration of fluorobenzamide (1) with 3,
in the presence of catalytic amounts of UO2ACHTNUTRGNEU(GN NO3)2·6H2O in
toluene, was studied as a model reaction to evaluate suitable
reaction conditions and to examine the effect of various re-
action parameters (Table 1). As expected, when using
Table 1. Uranium-catalyzed dehydration of 4-fluorobenzamide (1).
Entry[a]
Catalyst loading
[mol%]
Solvent
T
[8C]
t
MSTFA
ACHTUNGTRNE[NUNG equiv]
Yield
[%][b]
G
[h]
1
2
3
4
5
6
7
8
–
5
5
5
5
1
5
5
5
5
5
1
5
5
1
0.5
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THP
dioxane
dioxane
THF
DME
DME
100
100
100
100
100
100
120
70
RT
100
100
100
70
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
3
–
1
2
3
3
3
3
3
3
3
3
3
3
3
3
<1
<1
28
91
>99
16
>99
26
<1
76
>99
32
48
9
10
11
12
13
14
15
16
À
tion of silanes (Si H) to force the dehydration. In systems
that contain metals and silanes, milder conditions are appli-
cable, but difficulties can arise from either the production of
hydrogen as a waste product and, in the presence of func-
tional groups, the metal silane combination can act as reduc-
ing reagent and therefore reduce the scope of the protocol.
As a consequence, highly active dehydration catalysts in
combination with silanes, which have no reduction abilities,
are a challenging task for current research. According to
our ongoing interest in transition-metal catalysis, we herein
wish to emphasize the value of a straightforward uranium
catalyst for the dehydration of primary amides applying N-
methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) as de-
100
100
100
>99
>99
17
DME
[a] Reaction conditions: 1 (0.72 mmol), UO2ACHTNUTRGNEU(NG NO3)2·6H2O (0.5–5 mol%),
MSTFA (1.0–3.0 equiv), solvent (2.0 mL), RT–1208C, 24 h. [b] Deter-
mined by GC methods using biphenyl as an internal standard.
MSTFA in the absence of UO
of 4-fluorobenzonitrile (2) was observed (Table 1, entry 1).
Moreover, UO2A(NO3)2·6H2O without MSTFA was not capa-
ble to perform the dehydration (Table 1, entry 2).
In contrast, in the presence of UO2A(NO3)2·6H2O
2ACHTUNGTRENNUN(G NO3)2·6H2O, no formation
CTHUNGTRENNUNG
CTHUNGTRENNUNG
(5.0 mol%) and MSTFA (3 equiv), an excellent yield of
>99% and a chemoselectivity of >99% were attained
under non-inert conditions after a reaction time of 24 h
(Table 1, entry 5), whereas with lower amounts of MSTFA
(1–2 equiv), a diminished yield was observed (Table 1, en-
tries 3 and 4). A decrease in reaction temperature to 708C
resulted in a decreased yield of 2, whereas at room tempera-
[a] Dr. S. Enthaler
Technische Universitꢀt Berlin, Department of Chemistry
Cluster of Excellence “Unifying Concepts in Catalysis”
Strasse des 17. Juni 115, 10623 Berlin (Germany)
Fax : (+49)3031429732
Supporting information for this article is available on the WWW
9316
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9316 – 9319