Highly efficient one-pot synthesis of primary amides catalyzed by scandium(III) triflate under controlled MW

Article abstract of DOI:10.1016/j.tetlet.2011.08.150

The present Letter highlights a versatile synthetic protocol for the one-pot synthesis of primary amides employing scandium(III) triflate as a catalyst in water under controlled MW. This methodology offers excellent yields in shorter reaction times with enhanced selectivity.

Full text of DOI:10.1016/j.tetlet.2011.08.150

Tetrahedron Letters 52 (2011) 5851–5854
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Highly efficient one-pot synthesis of primary amides catalyzed by scandium(III)
triflate under controlled MW
⇑
Bharat Kumar Allam, Krishna Nand Singh
Department of Chemistry (Centre of Advanced Study), Faculty of Science, Banaras Hindu University, Varanasi 221005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The present Letter highlights a versatile synthetic protocol for the one-pot synthesis of primary amides
employing scandium(III) triflate as a catalyst in water under controlled MW. This methodology offers
excellent yields in shorter reaction times with enhanced selectivity.
Received 27 June 2011
Revised 23 August 2011
Accepted 25 August 2011
Available online 31 August 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
One-pot synthesis
Aldehyde
Amide
Sc(OTf)
Microwave
3
Amides are principally significant compounds that serve as
(
10 mol%) Sc(OTf)3
R
CHO + NH OH.HCl
a-1r
RCONH2
2a-2r
important synthetic raw materials in several industrial, engineer-
2
MW (300W), Na CO , H O,
ing, and pharmaceutical applications.1 The amide group is a
2
3
2
1
1
35 °C, 15-35min
high-flying functional ornamentation, artistic with well-heeled
chemistry and found in numerous bioactive molecules.2 The apt-
ness of efficient and sustainable methods for the synthesis of
amides has been considered to be an attractive area. Transition
metal-mediated organic transformations have been a current focus
for synthetic chemists,3 and therefore it is intended to recognize
transition metal catalysts that could be useful in industrial milieu
and also in terms of sustainability. An ideal catalyst would be of
low cost, limited toxicity and insensitive to air and moisture. In
light of these conditions, we turned our attention to stable Lewis
acid catalysts that have been extensively used in synthetic organic
chemistry, especially in the perspective of green chemistry. Cata-
R = Aryl, allyl, alkyl
3
Scheme 1. Sc(OTf) -catalyzed synthesis of primary amides under MW.
and aldehydes are often accompanied as by-products. This is
usually considered to be a severe drawback for industrial applica-
tions. To date, the conversion of aldehydes to amides has been
achieved with a very few transition metal complexes and salts
6
7
8
9
viz., Rh(OH)
x
/Al
2
O
3
, [Ir(Cp)Cl
2
]
2
, Pd(OAc)
2 3 3 2
, In(NO ) /ZnCl , Ter-
10
11
pyRu(PPh )Cl
3
2
,
3
and FeCl .
Although the reported methods have
3
lytic chemistry of scandium triflate [Sc(OTf) ] has recently been
their own advantages and disadvantages but most of them invari-
ably suffer from longer reaction times, use of costly and toxic metal
salts/ligands and use of undesired organic solvents.
4
described to be quite attractive and fascinating, and has been
exploited for a great number of diverse reactions, namely, allyla-
tion, aldol condensation, Diels–Alder reactions, Biginelli condensa-
tion, Ugi three-component coupling, many protection reactions
such as tetrahydropyranylation, O-glycosidation, and esterification
Water is considered to be a precious green solvent for organic
12–14
transformations because of its unique advantages.
The use of
microwave energy to drive chemical reactions is growing at a rapid
rate, with new and innovative applications in organic synthesis.
The assessment of green chemistry principles thus may have a di-
rect relevance for microwave synthesis in water.
As a part of our ongoing interest in the catalytic application of
transition metal salts in organic synthesis, we report herein a
5
of alcohols.
15
The transformation of aldoximes to primary amides is espe-
cially exigent and involves the use of reactive reagents in excess
quantities. The selectivity toward the formation of the desired
primary amide is often very low since nitriles, carboxylic acids,
16
convenient method for the one-pot synthesis of primary amides
in the presence of Sc(OTf)
microwave irradiation (Scheme 1).
3
in aqueous media under controlled
⇑
Corresponding author. Tel.: +91 542 6702485; fax: +91 542 2368127.
E-mail addresses: knsingh@bhu.ac.in, knsinghbhu@yahoo.co.in (K.N. Singh).
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.150

5
852
B. K. Allam, K. N. Singh / Tetrahedron Letters 52 (2011) 5851–5854
Table 1
Evaluation of reaction conditions for the model reaction between benzaldehyde and hydroxylamine hydrochloride
Entry
Catalyst (mol %)
Base (mol %)
Solvent
Conventional
MW irradiation
Power (W)
Temp (°C)
Time (h)
Yield (%)
Temp (°C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
—
—
H
2
O
100
135
135
100
100
100
110
100
100
100
100
110
100
100
100
100
100
135
100
100
100
100
24
24
24
24
24
24
24
24
24
24
24
24
24
24
18
18
24
24
24
24
24
24
—
37
70
45
Trace
Trace
Trace
20
—
—
Trace
20
18
79
92
90
60
63
68
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
135
135
135
135
135
135
135
135
135
135
135
135
135
135
135
135
135
135
135
135
135
135
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
—
Co(OAc)
Co(OAc)
Co(OAc)
2
2
2
Á4H
Á4H
Á4H
2
2
2
O [10]
O [20]
O [20]
NaHCO
NaHCO
NaHCO
3
3
3
[100]
[100]
[100]
[100]
[100]
[100]
[100]
(100)
[100]
[100]
[100]
[100]
[100]
[100]
[100]
[100]
[100]
[100]
C
C
6
H
H
5
Cl
Cl
61
84
53
15
27
20
29
—
6
5
H
2
H
2
H
2
O
O
O
MnCl
PTSA [10]
[10]
2
Á4H
2
O [10]
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
2
2
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
P
2
O
5
C
6
H
5
CH
3
3
3
Silica Sulfuric Acid [10]
CAN [10]
CeCl
CdCl
GaCl
LiClO
H
2
H
2
H
2
H
2
O
O
O
O
1
1
1
1
1
1
1
1
1
1
2
2
2
3
Á7H
2
O [10]
—
2
[10]
[10]
[10]
20
32
25
85
94
94
69
73
81
70
78
62
3
C
6 5
H
CH
4
H
2
H
2
H
2
H
2
O
O
O
O
Sc(OTf)
Sc(OTf)
3
[5]
3
[10]
[20]
[10]
[10]
[10]
[10]
[10]
[10]
Na
2
CO
3
Sc(OTf)
Sc(OTf)
Sc(OTf)
Sc(OTf)
Sc(OTf)
Sc(OTf)
Sc(OTf)
3
3
3
3
3
3
3
Na
Na
Na
2
CO
2
CO
2
CO
3
3
3
C
C
6
H
H
5
CH
Cl
6
5
NaHCO
CO [100]
DABCO [100]
-Proline [100]
3
H
2
H
2
H
2
H
2
O
O
O
O
K
2
3
51
65
55
L
Table 2
Sc(OTf)
-catalyzed one-pot synthesis of primary amides from aldehydes in watera
3
Entry
Substrate
Product
Conventional
Microwave
Time (min)
Time (h)
Yieldb (%)
Yieldb (%)
94
O
O
1
2
1a
1b
2a
18
92
30
15
NH2
O
O
O
O
NH2
2b
2c
11
19
86
84
89
88
O
Br
O
3
1c
NH2
30
Br
Br
O
O
O
O
4
5
1d
1e
2d
2e
21
20
83
87
35
35
86
90
Br
Cl
NH2
NH2
Cl
Cl
O
O
6
7
1f
NH2
2f
24
18
82
79
40
30
85
82
Cl
Cl
O
O
O
1g
NH2
NH2
2g
Cl
O
N
F
8
9
1h
2h
15
86
15
87
N
O
O
1i
1j
NH2
2i
2j
20
4
85
90
27
15
91
90
F
O
O
O
1
0
1
NH2
NH2
O
NO2
O
O
1
1k
2k
10
89
20
92
NO2

B. K. Allam, K. N. Singh / Tetrahedron Letters 52 (2011) 5851–5854
5853
Table 2 (continued)
Entry Substrate
Product
Conventional
Time (h)
Yieldb (%)
Microwave
Time (min)
Yieldb (%)
O N
O
2
O
1
2
1l
NH2
2l
7
90
20
95
O N
2
O
O
1
1
3
4
1m
1n
2m
2n
22
26
81
83
30
27
85
83
NH2
O
O
NH2
O
O
O
O
O
O
NH2
1
1
5
6
1o
1p
2o
2p
16
8
86
89
30
17
89
91
O
O
O
O
S
NH2
O
S
Cl
Cl
1
1
7
8
O
1q
1r
NH2
2q
2r
18
12
85
87
25
20
90
92
Cl
Cl
O
O
NH2
a
2 3 2 3
Reactions performed in H O with Sc(OTf) [10 mol %] and Na CO (1 equiv) at 100 °C under reflux and at 135 °C under MW (300 W).
Isolated yield after column chromatography of the crude product.
b
The process has been proved to be efficient, rapid, and offers
stability toward water. Altering the molar concentration of the cat-
alyst and employing different solvents and bases, under different
conventional and MW conditions did not improve the yield of
the product further.
excellent yields in shorter reaction times. First of all, we started
our exploration by undertaking the model reaction between benz-
aldehyde and hydroxylamine hydrochloride to optimize the reac-
tion conditions with particular reference to catalyst, base,
solvent, MW power, time, and temperature under conventional
as well as MW irradiation. The results were shortened in Table 1.
As it is evident, no product was observed in the absence of catalyst
and base both under conventional and microwave conditions (Ta-
ble 1, entry 1).
Under the optimized set of reaction conditions, different alde-
hydes (1a–1r) having varying structural features were made to re-
act with hydroxylamine hydrochloride to broaden the scope of the
reaction to afford corresponding primary amides (2a–2r) in excel-
1
7
lent yields (82–95%, Table 2, entries 1–17).
In conclusion, a convenient and effective direct one-pot route to
primary amides from aldehydes has been developed using Sc(OTf)
When the reaction was conducted in the presence of 10 mol %
3
Co(OAc)
2
Á4H
2
O/NaHCO
3
in chlorobenzene under reflux, it gave rise
as catalyst under MW. The overall process offers excellent yields in
shorter reaction times.
to 37% yield under conventional conditions (24 h) and 61% yield
under microwave (300 W, 135 °C, 30 min) (cf. Table 1, entry 2). Un-
der the same set of reaction conditions, however, when the molar
Acknowledgment
proportion of the catalyst Co(OAc)
2
Á4H
2
O was enhanced to
2
0 mol %, it gave rise to a considerable increase in the product yield
The authors are grateful to the Council of Scientific & Industrial
Research, New Delhi for financial assistance.
amounting to 70% under conventional and 84% yield under micro-
wave conditions (cf. Table 1, entry 3). Further increase in the con-
centration of Co(OAc)
product further. Among the solvents tried with Co(OAc)
chlorobenzene showed the best result. Out of other catalytic sys-
tems tried, CAN/Na CO and CeCl O/Na CO did not promote
Á7H
the reaction under reflux and MW conditions (cf. Table 1, entries
, 10). With MnCl O/Na CO , PTSA/Na CO , P /Na CO , and
Á4H
CdCl /Na CO , a trace of the desired product was observed under
reflux and a slight improvement in the product yield was seen un-
der MW (cf. Table 1, entries 5, 6, 7, 11). Further, silica sulfuric acid/
2 3 3 2 3 4 2 3
Na CO , GaCl /Na CO , and LiClO /Na CO provided very low
2
Á4H
2
O did not improve the yield of the
References and notes
2
Á4H O,
2
1
.
.
(a) Opsahl, R. In Encyclopedia of Chemical Technology; Kroschwitz, J. I., Ed.;
Wiley: New York, 1991; Vol. 2, pp 346–356; (b) Mabbermann, C. E. In
Encyclopedia of Chemical Technology; Kroschwitz, J. I., Ed.; Wiley: New York,
1991; Vol. 2, pp 251–256; (c) Lipp, D. In Encyclopedia of Chemical Technology;
Kroschwitz, J. I., Ed.; Wiley: New York, 1991; Vol. 2, pp 266–287.
(a) Fish, P. V.; Allan, G. A.; Bailey, S.; Blagg, J.; Butt, R.; Collis, M. G.; Greiling,
D.James, K.; Kendall, J.; McElroy, A.; McCleverty, D.; Reed, C.; Webster, R.;
Whitlock, G. A. J. Med. Chem. 2007, 50, 3442–3456; (b) Sugiyama, H.;
Yoshida, M.; Mori, K.; Kawamoto, T.; Sogabe, S.; Takagi, T.; Oki, H.; Tanaka,
T.; Kimura, H.; Ikeura, Y. Chem. Pharm. Bull. 2007, 55, 613–624; (c) Balunas,
M. J.; Linington, R. G.; Tidgewell, K.; Fenner, A. M.; Urena, L. –D.; Togna, G.
D.; Kyle, D. E.; Gerwick, W. H. J. Nat. Prod. 2010, 73, 60–66; (d) Sugawara, F.;
Strobel, S.; Strobe, G. J.; Larsen, R. D.; Berglund, D. L.; Gray, G.; Takahashi, N.;
Coval, S. J.; Stout, T. J.; Clardy, J. J. Org. Chem. 1991, 56, 909–910; (e)
Gamache, D. A.; Graff, G.; Brady, M. T.; Spellman, J. M.; Yanni, J. M.
Inflammation 2000, 24, 357–370; (f) Spaia, S.; Magoula, L.; Tsapas, G.;
Vayonas, G. Perit. Dial. Int. 2000, 20, 47–52.
2
3
3
2
2
3
9
2
2
2
3
2
3
2
O
5
2
3
2
2
2
3
yields under conventional conditions, albeit a slight increase under
MW (cf. Table 1, entries 8, 12, 13).
To our utmost surprise, when the catalytic activity of Sc(OTf)
CO in water was investigated, the reaction was endowed with
an excellent product yield of 92% under reflux condition (18 h) and
3
/
Na
2
3
3
4
.
.
Allen, C. L.; Williams, J. M. J. Chem. Soc. Rev. 2011. doi:10.1039/c0cs00196a.
(a) Alajarin, M.; Marin-Luna, M.; Vidal, A. Adv. Synth. Cat. 2011, 353, 557–562;
9
3
4% under controlled microwave irradiation (300 W, 135 °C,
0 min) using 10 mol % Sc(OTf) with 100 mol % Na CO (Table 1,
has excellent
3
2
3
(b) Wang, Z.; Yang, Z.; Chen, D.; Liu, X.; Lin, L.; Feng, X. Angew. Chem. 2011, 123,
5030–5034; (c) Singh, R.; Panda, G. Org. Biomol. Chem. 2010, 8, 1097–1105; (d)
entry 15). It is important to mention that Sc(OTf)
3

5
854
B. K. Allam, K. N. Singh / Tetrahedron Letters 52 (2011) 5851–5854
Böb, E.; Hillringhaus, T.; Nitsch, J.; Klussmann, M. Org. Biomol. Chem. 2011, 9,
744–1748; (e) Subba Reddy, B. V.; Ganesh, A. V.; Siva Krishna, A.; Narayana
Chemical Society: Washington, DC, 1994; (b) Organic Synthesis in Water In
1
Grieco, P. A., Ed.; Blackie Academic & Professional: London, 1998; (c) Lubineau,
A.; Au g´ e, J. In Modern Solvents in Organic Synthesis; Knochel, P., Ed.; Springer:
Berlin, 1999; (d) Kobayashi, S.; Manabe, K. Acc. Chem. Res. 2002, 35, 209–217;
(e) Aqueous-Phase Organometallic Catalysis: Concepts and Applications In
Cornils, B., Herrmann, W. A., Eds.; Wiley-VCH: Weinheim, 2004; (f) Tan, J.-N.;
Li, H.; Gu, Y. Green Chem. 2010, 12, 1772–1782; (g) Bradley, D.; Williams, G.;
Cullen, A.; Fourie, A.; Henning, H.; Lawton, M.; Mommsen, W.; Nangu, P.;
Parker, J.; Renison, A. Green Chem. 2010, 12, 1919–1921; (h) Solhy, A.;
Elmakssoudi, A.; Tahir, R.; Karkouri, M.; Larzek, M.; Bousmina, M.; Zahouily,
M. Green Chem. 2010, 12, 2261–2267.
Kumar, G. G. K. S.; Yadav, J. S. Tetrahedron Lett. 2011, 52, 3342–3344; (f) Socha,
A. M.; Sello, J. K. Org. Biomol. Chem. 2010, 8, 4753–4756; (g) Liu, L.; Wei, L.;
Zhang, J. Adv. Synth. Cat. 2010, 352, 1920–1924; (h) Faita, G.; Mella, M.;
Toscanini, M.; Desimoni, G. Tetrahedron 2010, 66, 3024–3029; (i) Yadav, J. S.;
Subba Reddy, B. V.; Ganesh, A. V.; Narayana Kumar, G. G. K. S. Tetrahedron Lett.
2
010, 51, 2963–2966.
5
.
.
Ogawa, C.; Gu, Y.; Boudou, M.; Kobayashi, S. In Acid Catalysis in Modern Organic
Synthesis; Yamamoto, H., Ishihara, K., Eds.; Wiley-VCH: Weinheim, 2008; Vol. 2,
pp 589–620.
6
Fujiwara, H.; Ogasawara, Y.; Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed.
15. Moseley, J. D.; Kappe, C. O. Green Chem. 2011, 13, 794–806. and references cited
therein..
2
007, 46, 5202–5205.
7
8
9
.
.
.
Owston, N. A.; Parker, A. J.; Williams, J. M. J. Org. Lett. 2007, 9, 73–75.
Ali, Md. A.; Punniyamurthy, T. Adv. Synth. Cat. 2010, 352, 288–292.
Allen, C. L.; Burel, C.; Williams, J. M. J. Tetrahedron Lett. 2010, 51, 2724–2726.
16. (a) Allam, B. K.; Singh, K. N. Synthesis 2011, 1125–1131; (b) Raghuvanshi, D. S.;
Singh, K. N. Synlett 2011, 373–377.
17. General MW procedure: A mixture of Sc(OTf)
(1 mmol), NH
OHÁHCl (1 mmol, 69 mg) and Na
3
(10 mol %, 49 mg), aldehyde
CO (1 mmol) was placed in a
O (1 mL). The vial
1
1
1
1
0. Gnanamgari, D.; Crabtree, R. H. Organometallics 2009, 28, 922–924.
1. Gowda, R. R.; Chakraborty, D. Eur. J. Org. Chem. 2011, 2226–2229.
2. Li, C.-J.; Chen, L. Chem. Soc. Rev. 2006, 35, 68–82.
2
2
3
safe pressure regulation 10 mL pressurized vial containing H
2
was sealed with a ‘snap-on’ cap and irradiated in a single-mode CEM Discover
Bench Mate microwave reactor at 300 W and 135 °C for 15–35 min. After the
reaction was complete (periodic TLC monitoring), the mixture was allowed to
cool to room temperature and was extracted with EtOAc (3 Â 10 mL). The
3. (a) Li, C.-J. Chem. Rev. 1993, 93, 2023–2035; (b) Lindstrom, U. M. Chem. Rev.
2
002, 102, 2751–2772; (c) Li, C.-J. Chem. Rev. 2005, 105, 3095–3166; (d)
Pirrung, M. C. Chem. -Eur. J. 2006, 12, 1312; (e) Li, C.-J.; Chan, T. H.
Comprehensive Organic Reactions in Aqueous Media; John Wiley & Sons Inc.:
Hobaken, NJ, 2007.
2 4
combined organic phase was dried over Na SO , filtered and the solvent was
removed under vacuum. The leftover residue was purified by column
chromatography on silica gel (EtOAc/hexane 3:7 as eluent) and then
characterized based on their physical and spectral data.
1
4. (a) Blokzijl, W.; Engberts, J. B. F. N. In Structure and Reactivity in Aqueous
Solution; Cremer, C. J., Truhlar, D. G., Eds.; ACS Symp. Ser. No. 568; American