Palladium-catalyzed one-pot conversion of aldehydes to amides

Article abstract of DOI:10.1002/adsc.200900799

The palladium-catalyzed one-pot conversion of aldehydes into primary amides in the presence of hydroxylamine hydrochloride in aqueous dimethyl sulfoxide (DMSO) at moderate temperature is described. The process is selective and free from the addition of an external chelating ligand.

Full text of DOI:10.1002/adsc.200900799

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DOI: 10.1002/adsc.200900799
Palladium-Catalyzed One-Pot Conversion of Aldehydes to
Amides
Md Ashif Alia and Tharmalingam Punniyamurthya,*
a
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India
Fax : (+91)-361-269-0762; e-mail: tpunni@iitg.ernet.in
Received: September 17, 2009; Published online: February 5, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900799.
Abstract: The palladium-catalyzed one-pot conver-
sion of aldehydes into primary amides in the pres-
ence of hydroxylamine hydrochloride in aqueous di-
methyl sulfoxide (DMSO) at moderate temperature
is described. The process is selective and free from
the addition of an external chelating ligand.
hydes to primary amides in refluxing toluene under
an inert atmosphere.[6] From an industrial standpoint,
these studies are attractive because the environmental
impact (E-factor) of the process can be lowered.[7]
Herein, we wish to report the one-pot transformation
of aldehydes with hydroxylamine hydrochloride to
primary amides using PdACHTNUTRGENNG(U OAc)2 as a catalyst in aque-
Keywords: aldehydes; homogeneous catalysis; one-
pot synthesis; palladium(II) acetate; primary
amides
ous dimethyl sulfoxide (DMSO) at moderate temper-
ature.[8,9] The present protocol is simple and general
for the conversion of alkyl, allyl and aryl aldehydes to
the corresponding primary amides. Furthermore, the
reactions are free from the addition of additives or
external chelating ligands.
First, the standardization of the protocol was car-
The recent development of metal catalysis with ad- ried out with 4-methoxybenzaldehyde as a model sub-
vanced properties has accelerated progress in the or- strate using Pd(OAc)2 in the presence of hydroxyl-
amine hydrochloride in different solvents and bases at
AHCTUNGTRENNUNG
ganic transformations of certain functional groups
ACHTUNGTRENNUNG
into more useful moieties.[1] Among these, the one- various temperatures (Table 1). We were pleased to
pot interconversion of aldehydes into primary amides find that the reaction occurred efficiently to afford
is one of the most important processes because of the desired 4-methoxybenzamide in 95% yield (100%
their utilities in a wide range of applications in aca- conversion) when the substrate was stirred at 1008C
demia and industry, especially as intermediates in or- using 5 mol% of PdACTHNUTRGNEUNG(OAc)2 in the presence of
ganic synthesis, raw materials for plastics, detergents, 1.2 equiv. of Cs2CO3 in a 3:1 mixture of DMSO and
lubricants and pharmaceuticals.[2] The classical meth- H2O. The ratio of DMSO and water was crucial for
ods used for this purpose, however, require stoichio- the outcome of the reaction. Pure organic solvents,
metric amounts of the reagents such as CH3SO3H DMSO, DMF and toluene, were found to be less ef-
(30 equiv. with respect to substrate),[3a] CH3SO2Cl fective providing the amide in <30% yield. Among
(1 equiv.)[3b] and ZnO (2 equiv.)[3c] with an excess of the bases, NaHCO3, Na2CO3, K2CO3 and Cs2CO3, the
hydroxylamine (>3 equiv.). To overcome these draw- latter provided the best results. Lowering of the reac-
backs, attention has been recently focused on the de- tion temperature (908C) or amount of the catalyst
velopment of catalytic systems for the transformation (2.5 mol%) led to the formation of the amide in
of aldehydes to primary amides in the presence of hy- <72% yield.
droxylamine.[4–6] Rh(OH)x/Al2O3 has been used as a
Next, the scope of the procedure was studied with
recyclable catalyst for the interconversion of alde- respect to the reactions of aryl, alkyl and allyl alde-
hydes to primary amides at 1608C in an autoclave.[4] hydes. Reactions of benzaldehyde and aryl aldehydes
Meanwhile [IrACHTUNGTRENNUNG(Cp*)Cl2]2 (Cp*=C5Me5) has also been having 2-Cl, 2-OEt, 2-OMe, 2-OC8H17, 3-Br, 3-NO2,
studied for the synthesis of amides from alcohols in 4-Br, 4-Cl, 4-F, 4-Me, 4-NO2, 3,4-di-OMe and 3,4,5-
toluene under reflux in the presence of a hydrogen tri-OMe substituents proceeded to give the respective
acceptor in an inert atmosphere.[5] Later, terpy-Ru- primary amide in 65–98% yield (Table 2). Similar re-
ACHTUNGTRENNUNG(PPh3)Cl2 has been examined for conversion of alde- sults were obtained with the reactions of 2-naphthal-
288
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Adv. Synth. Catal. 2010, 352, 288 – 292

Palladium-Catalyzed One-Pot Conversion of Aldehydes to Amides
Table 1. The standardization of the reaction conditions.
Entry
Solvent
Base
Temperature [8C]
Time [h]
Yield [%][a,b]
1
2
3
4
5
6
7
8
DMSO
DMF
toluene
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KOH
Cs2CO3
Na2CO3
NaHCO3
K2CO3
K2CO3
K2CO3
Cs2CO3
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
125
125
125
125
125
125
125
125
125
125
125
125
125
100
100
100
90
12
12
12
12
12
12
10
10
10
10
12
12
12
12
12
12
12
8
30
21
12
51
90
21
14
97
DMSO:H2O (9:1)
DMSO:H2O (3:1)
DMSO:H2O (1:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
DMSO:H2O (3:1)
9
16
14
10
11
12
13
14
15
16
17
18
78[c]
32[d]
75[e]
95
13
72[f]
70
100
14[g]
[a]
To a stirred solution of p-methoxybenzaldehyde (0.5 mmol), H2NOH·HCl (0.6 mmol) and base (0.6 mmol) in
DMSO:H2O (2 mL) for 5 h, Pd
Isolated yield.
Base (1.5 equiv.) was used.
H2NOH·HCl (1 equiv.) was used.
H2NOH·HCl (1.5 equiv.) was used.
ACHTUNGRTEN(NUNG OAc)2 (5 mol%) was added and the reaction mixture was stirred for 5–7 h.
[b]
[c]
[d]
[e]
[f]
Pd
Pd
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
[g]
dehyde and heteroaromatic aldehydes such as picoli- are independent with respect to air or nitrogen atmos-
naldehyde, furan-2-carbaldehyde, thiophene-2-carbal- phere. Thus, the reaction of the aldehyde with hy-
dehyde
and
8-methoxyquinoline-2-carbaldehyde droxylamine can give aldoxime which can undergo re-
(OAc)2 to give intermediate a
(Table 2). In addition, aliphatic aldehydes, acetalde- action with Pd
U
hyde, n-hexanal, 2-propanal, and cyclohexanecarbal- (Scheme 3). The latter can transform into c via b to
dehyde as well as an allyl aldehyde, cinnamaldehyde, complete the catalytic cycle by dehydration and hy-
were transformed to the corresponding primary dration processes.
amide in high yield (Table 3). These results suggest
In conclusion, a simple, general and practical one-
that the protocol is general and aryl, alkyl and allyl al- pot protocol is described for interconversion of aryl,
dehydes can be transformed to the corresponding pri- alkyl and allyl aldehdyes into primary amides using
mary amides.
PdACTHUNGRETNNU(G OAc)2 in a DMSO and H2O mixture under air.
In these reactions, the aldehydes first undergo reac- The reactions are selective and no by-product forma-
tion with hydroxylamine hydrochloride in the pres- tion is observed.
ence of base to give aldoximes[10] that are transformed
into amides by dehydration and hydration proces-
ses.[10h] For example, when a 1:1 mixture of benzalde-
hyde and benzonitrile was subjected to the optimized
conditions, both the substrates were transformed into
benzamide in 100% conversion and selectivity
(Scheme 1). The reaction of benzaldehyde with hy-
droxylamine hydrochloride in the presence of molecu-
lar sieve 3 ꢁ in dry DMSO gave a trace of amide
(<5%) along with benzonitrile (30%) and phenyl-
ACHTUNGTRENNUNGaldoxime (65%) (Scheme 2). Moreover, the reactions DMSO-H2O.
Scheme 1. The reaction of benzaldehyde and benzonitrile in
Adv. Synth. Catal. 2010, 352, 288 – 292
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289

Md Ashif Ali and Tharmalingam Punniyamurthy
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Table 2. Pd-catalyzed conversion of aryl aldehydes to amides.
[a]
To a stirred solution of aldehyde (0.5 mmol), H2NOH·HCl (0.6 mmol) and Cs2CO3 (0.6 mmol) in DMSO:H2O (3:1, 2 mL)
at 1008C for 5–7 h, PdACHTNUTRGNENG(U OAc)2 (5 mol%) was added and the reaction mixture was stirred for additional 5–19 h.
Isolated yield.
[b]
Experimental Section
General Procedure for Pd-Catalyzed Conversion of
Aldehydes to Primary Amides
Aldehyde (0.5 mmol), NH2OH·HCl (0.6 mmol) and Cs2CO3
(0.6 mmol) were stirred at 1008C for 5–7 h in a 3:1 mixture
of DMSO-H2O (2 mL) under air. Then, PdACTHNUTRGNEG(NU OAc)2 (5 mol%)
was added and the stirring continued for the appropriate
time (Table 2 and Table 3). The progress of the reaction was
monitored by TLC using ethyl acetate and hexane as eluent.
After completion, the reaction mixture was cooled to room
temperature and treated with water (1 mL). The resulting
mixture was extracted with ethyl acetate (3ꢂ5 mL). Drying
(Na2SO4) and evaporation of the solvent gave a residue that
was purified on silica gel column chromatography using
ethyl acetate and hexane. The products were characterized
by NMR (1H and 13C), IR and CHN analysis.
Scheme 2. The reaction in dry DMSO with molecular sieves
3 ꢁ.
290
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Adv. Synth. Catal. 2010, 352, 288 – 292

Palladium-Catalyzed One-Pot Conversion of Aldehydes to Amides
Scheme 3. Proposed catalytic cycle.
Table 3. Pd-catalyzed conversion of alkyl and allyl aldehydes
to amides.
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We thank Department of Science and Technology, New
Delhi, and Council of Scientific and Industrial Research,
New Delhi, for financial support.
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Adv. Synth. Catal. 2010, 352, 288 – 292