Rh-catalyzed one-pot and practical transformation of aldoximes to amides

Article abstract of DOI:10.1039/b305268k

Wilkinson's complex has been found to catalyze the one-pot transformation of aldoximes to the corresponding amides with high selectivity and efficiency under essentially neutral conditions.

Full text of DOI:10.1039/b305268k

Rh-Catalyzed one-pot and practical transformation of aldoximes to
amides
Soyoung Park,a Yoon-aa Choi,a Hoon Han,a Soon Ha Yangb and Sukbok Chang*a
a Center for Molecular Design and Synthesis, Department of Chemistry and, School of Molecular Science
(BK21), Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
E-mail: sbchang@mail.kaist.ac.kr
b Department of Chemistry, Ewha Womans University, Seoul 120-705, Korea
Received (in Cambridge, UK) 14th May 2003, Accepted 17th June 2003
First published as an Advance Article on the web 1st July 2003
Wilkinson’s complex has been found to catalyze the one-pot
transformation of aldoximes to the corresponding amides
with high selectivity and efficiency under essentially neutral
conditions.
: 6).8 The catalytic activity and selectivity of the Wilkinson
catalyst was slightly improved when the reaction was carried
out in toluene under otherwise identical conditions ( > 95%
conversion, nitrile : amide, 1 : > 9). When the reaction was
carried out at lower temperatures, benzamide was obtained in
lower yields due to slower conversion: 89% (150 °C, 4 h), 57%
(130 °C), and 43% yield (110 °C).9
Next, we investigated the scope and generality of the above
RhCl(PPh3)3-catalyzed conversion of aldoximes to amides (see
Table 1). Aldoximes used in this study were quantitatively
prepared from the reaction of the corresponding aldehydes with
hydroxylamine hydrochloride. Aldoximes were used as a
mixture of Z- and E-isomers though in most cases the E-form is
the major isomer. Benzaldoximes with substituents of varying
electronic properties were all smoothly converted to the
corresponding amides in high yields (entries 1–6) and only
negligible amounts of nitriles were obtained. Regardless of the
electronic properties of substituents on aldoximes, the reaction
resulted in high efficiency and selectivity. Several functional
groups including ester moieties were tolerated under the
Studies on organic transformations of certain functional groups
into more useful moieties have been recently accelerated mainly
due to the development of transition metal catalysts with
advanced properties.1 Among these, the inter-conversion of
carbonyl groups and their equivalents is one of the most
important processes in organic synthesis. Although numerous
reagents have been introduced for these reactions,2 efforts
aimed at developing more efficient and practical catalytic
systems are still actively underway for various reasons
including economic and environmental. During our studies on
metal-catalyzed reactions,3 we have recently reported that
aldoximes can be readily dehydrated under mild conditions to
afford nitriles using a Ru catalyst (Scheme 1, eqn. 1).4 Based on
this result, we have tried to find a new catalytic system for the
subsequent conversion of nitrile to amide. Instead of the
plausible two-step sequence, however, we have found that a net
transformation of aldoximes to the corresponding amides can be
readily achieved in one-pot† by rhodium catalysis with high
selectivity and efficiency (Scheme 1, eqn. 2), which is described
in this communication.5
Table 1 Rh-Catalyzed one-pot conversion of aldoximes to amidesa
We first investigated the catalytic activities of a diverse range
of metal complexes for the transformation of benzaldoxime.
Although some metal catalysts showed measurable activities for
conversion of the aldoxime to the corresponding nitrile under
certain conditions, subsequent in situ catalytic hydrolysis of
nitrile adduct turned out to be more difficult to perform.7 For
example, when benzaldoxime was treated with [RuCl2(p-
cymene)]2 catalyst (5 mol%) in DMF over 4 h at 150 °C,
conversion was incomplete (53%) in the absence of any
additives such as molecular sieves, and the ratio of formed
benzonitrile to benzamide was determined to be 1 : 2. Other
ruthenium catalysts examined displayed rather lower activities
or decreased selectivities under the same conditions:
RuH2(PPh3)4 (77% conversion, 1 : 1),6 Ru3(CO)12 (19%
conversion, 3 : 1), and RuCl3 (67% conversion, 1 : 1). In
contrast, rhodium catalysts exhibited enhanced selectivity for
the generation of benzamide compared to the ruthenium
complexes.
Entry
R
Solvent
t/h
Yield (%)b
1
2
3
4
5
6
7
C6H5
Toluene
Toluene
Toluene
Toluene
Toluene
DMF
2
2
2
4
4
5
2
89
78
78
80
85
73
80
(4-Br)C6H4
(4-NO2)C6H4
(4-BnO)C6H4
(4-BnO2C)C6H4
(2,6-Cl)C6H3
DMF
8
9
Toluene
DMF
5
5
5
93
84
74
10
DMF
Some examples are: [Rh(OAc)2]2 (in DMF, 150 °C, 4 h, 88%
conversion, nitrile : amide, 1 : 4), [RhCl(cod)]2 (67%, 1 : 4),
[(PPh3)3Rh(nbd)]+ PF62 (77%, 1 : 6), and RhCl(PPh3)3 (92%, 1
11
12
13
Cyclohexyl
C6H5(CH2)2
Toluene
Toluene
Toluene
5
5
5
87
98
94
14
DMF
4
94c
a See the Notes and references† for a typical experimental procedure.
b Isolated yields after crystallization or chromatography on silica gel.
c Yield of isolated bisamide (1,4-benzenedicarboxamide) starting from
1,4-bisaldoxime.
Scheme 1 Selective conversion of aldoximes to nitriles or amides.
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conditions (entry 5). Sterically congested aldoximes such as
2,6-dichlorobenzaldoxime were also readily converted to the
corresponding amide in good yield (entry 6).
In summary, a highly efficient and selective catalytic
protocol has been developed for the one-pot conversion of
aldoximes to amides under essentially neutral conditions,
which, to the best of our knowledge, has not been reported
previously. The procedure is characterized to be atom-
economical13 and environmentally friendly14 because the
transformation occurs in the absence of any additives except for
catalyst and it does not generate any by-products.
The presence of heteroatoms including S, O, and N in the
substrates did not alter the efficiency or selectivity, and a range
of heteroaromatic amides were obtained in good yields (entries
7–10). It should be mentioned that syn-aldoximes react faster
than the corresponding anti-isomer, and enrichment of the anti-
isomer in the early stages was observed. For example, when
2-thiophene-syn-aldoxime10 was allowed to react, 80% conver-
sion was observed over 30 min (toluene, 130 °C, 1 mol%
Wilkinson catalyst). In contrast, conversion of the anti-isomer
was much lower (19%) and isomerization to the syn-aldoxime
was observed to occur to some extent. Not only aromatic but
also aliphatic aldoximes could be employed as facile substrates
for the transformation (entries 11–12). Whereas toluene was
used as a facile solvent in general, DMF turned out to be more
suitable for substrates of poor solubility such as pyridyl-
containing aldoximes (entries 9–10). A conjugated aldoxime
such as trans-cinnamaldehyde oxime was also readily con-
verted to the conjugated amide (entry 13). As shown in entry 14,
when a substrate bearing a bisaldoxime group was treated with
the rhodium catalyst, a satisfactory yield of the corresponding
bisamide was obtained.
Although the exact pathway of the Rh-catalyzed transforma-
tion is not clear at the present stage, two plausible scenarios can
be suggested on the basis of the experimental results. The first
involves a nitrile intermediate. Formation of amides from
aldoximes under the conditions used was accompanied by
generation of nitriles as a by-product albeit in small amounts
( < 8%) in most substrates examined. Moreover, the Rh complex
catalyzes hydrolysis of benzonitrile to benzamide though the
efficiency was lower (H2O 3 equiv., Rh 10 mol%, 150 °C, 12 h,
toluene, 55% benzamide) compared to that under the one-pot
conditions. The fact that ketoximes and O-alkyl aldoximes were
intact under the conditions would be additional indirect
evidence for the nitrile intermediacy. Another possible route, a
direct rearrangement of aldoximes to nitriles by action of the
rhodium catalyst, can also be envisaged to operate either
exclusively or in parallel with the above stepwise pathway.11
When the reaction was carried out in the presence of water (3
equiv. to aldoxime), the reaction rate and selectivity were little
changed compared to those of the anhydrous conditions. The
fact that even when water scavenger such as MS (4 Å, 3 equiv.
to benzaldoxime) was added, amide was still produced albeit in
lower yield (52%, 48 h, 150 °C) would be an additional outcome
favoring the direct rearrangement pathway. Dehydration of
amides to the corresponding nitrile precursors was not catalyzed
by the Ru or Rh complexes examined.12
This work was supported by a Korean Research Foundation
Grant (KRF-2001-041-D00147). We thank one reviewer for
helpful suggestions regarding the mechanistic aspects.
Notes and references
† Typical procedure for rhodium-catalyzed one-pot conversion of aldox-
imes to amides: To a solution of 4-bromobenzaldoxime (400.0 mg, 2.0
mmol) in toluene (0.5 mL) was added RhCl(PPh3)3 (93 mg, 0.1 mmol), and
the mixture was stirred for 2 h at 150 °C. After completion of the reaction,
which was checked by TLC, analytically pure 4-bromobenzamide (312 mg,
78%) was obtained after recrystallization from diethyl ether.
1 For general reviews, see: (a) Comprehensive Organometallic Chemistry
II, ed. E. W. Abel, F. G. A. Stone and G. Wilkinson, Pergamon, Oxford,
1995; (b) B. Cornils and W. A. Hermann, Applied Homogeneous
Catalysis with Organometallic Compounds, VCH, New York, 1996; (c)
Transition Metals for Organic Synthesis, ed. M. Beller and C. Bolm,
Wiley-VCH, Weinheim, 1998.
2 R. C. Larock, Comprehensive Organic Transformations, Wiley-VCH,
New York, 1999, 2nd edn., p. 1929.
3 (a) Y. Na and S. Chang, Org. Lett., 2000, 2, 1887; (b) M. Lee and S.
Chang, Tetrahedron Lett., 2000, 41, 7507; (c) M. Lee, S. Ko and S.
Chang, J. Am. Chem. Soc., 2000, 122, 12011; (d) S. Chang, Y. Na, E.
Choi and S. Kim, Org. Lett., 2001, 3, 2089; (e) S. Ko, Y. Na and S.
Chang, J. Am. Chem. Soc., 2002, 114, 750.
4 S. H. Yang and S. Chang, Org. Lett., 2001, 3, 4209.
5 Some examples of transformations of oximes: (a) A. S. Demir, C.
Tanyeli and E. Altinel, Tetrahedron Lett., 1997, 38, 7267; (b) Z. Jie, V.
Rammoorty and B. Fischer, J. Org. Chem., 2002, 67, 711.
6 For RuH2(PPh3)4-catalyzed hydration of nitriles to amides, see: (a) S.-I.
Murahashi, S. Sasao, E. Saito and T. Naota, J. Org. Chem., 1992, 57,
2521; (b) S.-I. Murahashi, S. Sasao, E. Saito and T. Naota, Tetrahedron,
1993, 49, 8805; (c) H. J. P. de Lijser, F. H. Fardoun, J. R. Sawyer and
M. Quant, Org. Lett., 2002, 4, 2325.
7 For
a selected example of biotransformation of nitriles to the
corresponding amides, see: M.-X. Wang and S.-J. Lin, Tetrahedron
Lett., 2001, 42, 6925.
8 A rhodium carbonyl cluster was previously used to catalyze deoxygen-
ation of aldoximes in the presence of CO and H2, see: K. Kaneda, K.
Doken and T. Imanaka, Chem. Lett., 1988, 285.
9 Catalytic hydration of nitriles to amides by water-soluble rhodium
complexes under basic conditions (pH
~ 11.7) has been recently
reported, see: M. C. K.-B. Djoman and A. N. Ajjou, Tetrahedron Lett.,
2000, 41, 4845.
The adaptability of the present catalytic system to a large-
scale process was next examined. Complete conversion of
4-chlorobenzaldehyde oxime (26 mmol, 4.0 g) was achieved
with as low as 0.5 mol% of RhCl(PPh3)3 catalyst within 12 h
affording 4-chlorobenzamide in good yield (Scheme 2).
10 Two separable aldoxime isomers were characterized according to the
literature, see: S. G. Tandon and S. C. Bhattacharya, Anal. Chem., 1960,
32, 194.
11 One referee suggested that nucleophilic addition of catalytic amounts of
water to a coordinated Rh-aldoxime species followed by elimination of
water would also be worth consideration.
12 Recently, a procedure of rhenium-catalyzed dehydration for the
conversion of primary amides and aldoximes to nitriles has been
reported, see: K. Ishihara, Y. Furuya and H. Yamamoto, Angew. Chem.,
Int. Ed., 2002, 41, 2983.
13 B. M. Trost, Angew. Chem., Int. Ed. Engl., 1995, 34, 259.
14 P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice,
Oxford University Press, Oxford, 1998.
Scheme 2
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