P2O5/SiO2-catalyzed one-pot synthesis of amides from ketones via schmidt reaction under microwave irradiation in dry media

Article abstract of DOI:10.1080/00397910600638978

A facile and efficient method for the preparation of amides from ketones by the Schmidt reaction is described for the first time using P 2 O 5 /SiO 2 and sodium azide under solvent-free microwave irradiation. Advantages of this procedure are selectivity, good yields, a simple operation, short reaction time, and solvent-free conditions. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600638978

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P2O5/SiO2‐Catalyzed One‐Pot Synthesis of
Amides from Ketones via Schmidt Reaction
under Microwave Irradiation in Dry Media
Hossein Eshghi a b & Asadollah Hassankhani b
a Department of Chemistry, Ferdowsi University of Mashhad, Mashhad, Iran
b Department of Chemistry, Sistan and Baluchestan University, Zahedan, Iran
Published online: 16 Feb 2007.
To cite this article: Hossein Eshghi & Asadollah Hassankhani (2006) P2O5/SiO2‐Catalyzed One‐Pot Synthesis
of Amides from Ketones via Schmidt Reaction under Microwave Irradiation in Dry Media, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:15,
2211-2216, DOI: 10.1080/00397910600638978
To link to this article: http://dx.doi.org/10.1080/00397910600638978
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Synthetic Communicationsw, 36: 2211–2216, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600638978
P2O5/SiO2-Catalyzed One-Pot Synthesis of
Amides from Ketones via Schmidt Reaction
under Microwave Irradiation in Dry Media
Hossein Eshghi
Department of Chemistry, Ferdowsi University of Mashhad, Mashhad,
Iran and Department of Chemistry, Sistan and Baluchestan University,
Zahedan, Iran
Asadollah Hassankhani
Department of Chemistry, Sistan and Baluchestan University,
Zahedan, Iran
Abstract: A facile and efficient method for the preparation of amides from ketones by
the Schmidt reaction is described for the first time using P2O5/SiO2 and sodium azide
under solvent-free microwave irradiation. Advantages of this procedure are selectivity,
good yields, a simple operation, short reaction time, and solvent-free conditions.
Keywords: Amides, ketones, microwave irradiation, phosphorus pentoxide, Schmidt
reaction, silica gel
The acid-catalyzed reaction of carbonyl compounds with hydrazoic acid,
known as the Schmidt reaction, was first reported in 1923.[1] It is one of the
most classical and popular reactions in organic chemistry. This reaction is a
convenient method for the synthesis of a wide variety of nitrogen-containing
materials.[2] The classical Schmidt reaction of carbonyl compounds requires
an excess or stoichiometric amount of strong protic acids (such as concentrated
Received in the UK August 16, 2005
Address correspondence to Hossein Eshghi, Department of Chemistry, Ferdowsi
University of Mashhad, Mashhad 91775-1436, Iran. E-mail: heshghi@hamoon.
usb.ac.ir
2211

2212
H. Eshghi and A. Hassankhani
sulfuric acid,[3,4] polyphosphoric acid,[5] HBr,[6] or HCl[6]) or strong Lewis acid
(such as AlCl3,[6] POCl3,[6] or TiCl4[7]) and solvents (such as toxic benzene,[3,6]
nitrobenzene,[6] concentrated sulfuric acid,[3,6] polyphosphoric acid,[5] molten
trichloroacetic acid,[6,8] or glacial acetic acid[3]) over long reaction times.
The main disadvantages associated with classical procedures include the use
of hydrogen azide, which presents considerable experimental difficulties
because of its toxicity and possible explosion risks. Replacement of
hydrazoic acid by inorganic azides, which are poorly soluble in organic
solvents, causes an increase in reaction time and decrease in product yield.
To minimization this problem, recently we have reported the synthesis of
1,5-fused tetrazoles via the Schmidt reaction under solvent-free conditions.[9]
In recent years, solvent-free reactions using mineral solid supports
have received increasing attention. Among the solvent-free techniques,
microwave-accelerated organic synthesis is an effective route proposed
during the past decade because of drastic reduction of reaction time, easy
workup, and improved yields.[10]
In our ongoing research program to develop new synthetic method-
[11]
ologies, we have found that P2O5/SiO2
can be used for the Schmidt
reaction of carbonyl compounds under solvent-free conditions. To the best
of our knowledge, this report describes the first example of the direct
synthesis of amides from ketones via the Schmidt reaction under microwave
irradiation in solvent-free media (Scheme 1).
In an attempt to examine the Lewis acid property of P2O5/SiO2 in the solid
state, 4 mmol of propiophenone and 8 mmol of sodium azide were mixed with
1 g of P2O5/SiO2 reagent in an agate mortar, and then the uniform mixture was
irradiated by microwaves for 8 min. The corresponding anilide was obtained as
the only product in 92% yield. In the absence of microwave irradiation, after
30 min of grinding the reaction mixture at 608C, only 55% conversion was
observed and 45% of the starting material was recovered.
To prepare amides, various types of ketones were mixed with sodium
azide in the presence of P2O5/SiO2 and microwave irradiation in solvent-
free conditions. The corresponding anilides were obtained as the only
products in good yields. The general reaction is illustrated according to
Scheme 1, and the results have been reported in Table 1. All reactions were
performed in less than 10 minutes. As shown in Table 1, several structurally
varied ketones underwent clean, remarkably fast, and direct nitrogen insertion
reactions by a Schmidt reaction to the corresponding amides. This mild and
versatile method can also be applied for both aromatic and aliphatic
Scheme 1.

Amides from Ketones via Schmidt Reaction
2213
Table 1. One-pot preparation of amides from ketones using P2O5/SiO2 in solvent-free
conditions under microwave irradiationa
Time
(min)
Yield
(%)b
Entry
Substrate
Products
7
7
7
7
70
72
70
75
1
2
3
7
7
75
70
4
5
8
8
92
90
6
7
8
8
90
85
83
10
10
9
10
80c
(continued)

2214
H. Eshghi and A. Hassankhani
Table 1. Continued
Time
(min)
Yield
(%)b
Entry
Substrate
Products
10
10
10
91c
11
93c
aProducts were characterized by their physical constants, comparison with authentic
1
samples, and IR and H NMR spectra.[12]
bIsolated yields.
cRatio of the products were determined from 1H NMR spectra of the crude product.
ketones. Usually one of the isomeric products being obtained (entries 4–8).
Generally, migration of an aryl group predominates over that of an alkyl
group. In the other cases, the major product is the one where the more
bulky group has migrated (entries 9–11). Several cyclic ketones undergo
Schmidt reaction upon treatment with this catalyst to afford corresponding
lactams (entries 1–3). Products were characterized by their physical
constants, comparison with authentic samples, and IR and NMR spectra.[12]
In summary, we have developed a novel and efficient method for
synthesis of amides by the Schmidt reaction of ketones with sodium azide
using P2O5/SiO2 as a catalyst. This method offers several advantages
including mild reaction conditions, solvent-free media, operational simplicity,
short reaction times, high yields, and high selectivity without the formation of
by-products [13,14](e.g., tetrazoles, amino tetrazoles, nitriles, and ureas).
EXPERIMENTAL
All melting points recorded are uncorrected open-capillary measurements. IR
1
spectra were recorded on a Shimadzu-IR 470 spectrophotometer. H NMR
spectra were recorded on a Bruker-80 500-MHz instrument using tetramethyl-
silane (TMS) as an internal standard. Silica gel 60 (230–400 mesh) was
purchased from Fluka and was dried in an oven at 1208C for 2 h. Irradiation
was carried out in a domestic microwave oven (Electra, 2450 MHz, 400 W)
for optimized time.

Amides from Ketones via Schmidt Reaction
2215
Preparation of the P2O5/SiO2 Reagent
A mixture of phosphorus pentoxide (5 g) and chromatography-grade silica
gel (5 g) were placed in a flask and stirred for 4 h. This homogeneous,
free-flowing, white powder reagent is sensitive toward moisture and should
be stored in a dessicator.
General Procedure
In a typical reaction, a mixture of ketone (4 mmol), sodium azide (8 mmol),
and reagent (1 g) were grounded thoroughly in a mortar. The mortar was
covered with a watch glass and put inside an Electra microwave
(2450 MHz, 400 W). The mixture was irradiated for the time indicated in
Table 1. The completion of the reaction was monitored by TLC examination.
After the completion of the reaction, the mortar was removed from the oven
and the mixture was cooled at room temperature, and then water (10 ml)
was added to the mixture. The resulting solution was extracted with CH2Cl2
(2 Â 10 ml). The extracts were combined and dried over CaCl2. Evaporation
of the solvent under vacuum gave amides with high purity (entries 1–8)
1
(based on TLC, H NMR, IR, and melting point). Column chromatography
or recrystallization from EtOH could further purify the products of entries
(9–11).
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