An easy method for the generation of amides from ketones by a Beckmann type rearrangement mediated by microwave

Article abstract of DOI:10.1081/SCC-120022469

A facile and efficient procedure is developed for one-pot synthesis of amides from ketones in the presence of P₂O₅/SiO ₂ reagent in dry media under microwave irradiation. Ketoximes indirectly in the same conditions gave amides by Beckmann rearrangement.

Full text of DOI:10.1081/SCC-120022469

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An Easy Method for the Generation of Amides from
Ketones by a Beckmann Type Rearrangement Mediated
by Microwave
Hossein Eshghi a & Zinat Gordi a
a Department of Chemistry , Sistan and Baluchestan University , Zahedan, Iran
Published online: 21 Aug 2006.
To cite this article: Hossein Eshghi & Zinat Gordi (2003) An Easy Method for the Generation of Amides from Ketones by
a Beckmann Type Rearrangement Mediated by Microwave, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:17, 2971-2978, DOI: 10.1081/SCC-120022469
To link to this article: http://dx.doi.org/10.1081/SCC-120022469
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 17, pp. 2971–2978, 2003
An Easy Method for the Generation of Amides
from Ketones by a Beckmann Type
Rearrangement Mediated by Microwave
*
Hossein Eshghi and Zinat Gordi
Department of Chemistry, Sistan and Baluchestan
University, Zahedan, Iran
ABSTRACT
A facile and efficientprocedure is developed for one-potsynthesis of
amides from ketones in the presence of P2O5/SiO2 reagentin dry
media under microwave irradiation. Ketoximes indirectly in the
same conditions gave amides by Beckmann rearrangement.
Key Words: Amides; Ketones; Ketoximes; Beckmann type rearran-
gement; Microwave irradiation; P2O5/SiO2.
The Beckmann rearrangement of ketoximes has been used exten-
sively in organic synthesis[1] due to the simplicity at which the reaction
*Correspondence: Hossein Eshghi, Department of Chemistry, Sistan and
Baluchestan University, Zahedan, 98135-674, Iran; E-mail: heshghi@hamoon.
usb.ac.ir.
2971
DOI: 10.1081/SCC-120022469
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2972
Eshghi and Gordi
affects nitrogen insertion into a carbon framework and the fact that
the rearrangement is usually stereospecific. Several methods for this
rearrangement have been reported in the literature that include the use
of formic acid,[2] liquid SO2, HMPA,[3] SOCl2,[4] silica gel,[5] P2O5-
methanesulfonic acid,[6] HCl-HOAc, Ac2O,[7] polyphosphoric acid,[8]
AlCl3,[9] BiCl3,[10] and rhodium complex.[11]
On the other hand, chemical methods[12] for the synthesis of oximes
usually give a mixture of the two geometrical isomers, which must be
separated by chromatography or recrystallization techniques. However,
the reagents that have been used for oximation of ketones or Beckmann
rearrangement, also catalyze interconversion of this geometrical
isomers.[13] The stereochemistry of oxime in some cases are unimportant
and the mixture of products (one major) were obtained in Beckmann
rearrangement.[9,11] As
a
resuhltetre is always considerable
interest in finding more selective methods of oxime synthesis or direct
pathways.
Very few methods are available for direct amidation of ketones.[14–17]
Methods for simultaneous oximation of ketones and rearrangement to
the amides, in the case of cyclohexanone are known in the literature,
either with the use of hydroxylamine and sulfuric acid,[14] or by employ-
ing primary nitroparaffines as a source of hydroxylamine.[15] In the
former case, generally large excess of concentrated sulfuric acids is
required, which subsequently must be neutralized. This process is, thus,
unattractive in many cases, particularly in systems, which are sensitive to
sulfuric acid, as well as because of the required work up. In 1979,
G. Olah[16] reported a one-step conversion of alicyclic ketones into lac-
tams with hydroxylamine-O-sulfonic acid and formic acid under reflux
condition. Interestingly it was observed[17] that when this reaction was
carried outover SiO 2 under microwave irradiation, it gives an amino acid
salt, which cyclizes to the corresponding lactam after work up in basic
medium. But most of these have some disadvantages in relation to their
general applicability, selectivity, availability, operational convenience,
and toxicity.
Our project has been continually working on the basis of developing
of new synthetic methods using P2O5/SiO2 in solid phase.[18] Having the
above facts in mind, we wish to report a very simple and efficient method
for one-pot synthesis of amides from ketones using the P2O5/SiO2 reagent
in solid phase under microwave irradiation.
In an attempt to examine the Lewis acid property of P2O5/SiO2 in the
solid state, 2 mmol of cyclohexanone and 4 mmol of hydroxylamine
hydrochloride were mixed with 1 g of P2O5/SiO2 reagentin an agaet
mortar, and then the uniform mixture was irradiated by microwave for

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Beckmann Type Rearrangement of Ketones
2973
Scheme 1.
5 min. "-Caprolactam was obtained instead of cyclohexanone oxime, in
88% yield, which can be used in manufacture of polyamides such as
Nylon 6.[16]
In order to prepare amides, various types of ketones were mixed with
hydroxylamine hydrochloride in the presence of P2O5/SiO2 reagentusing
microwave irradiation in solid phase. In this approach, amides were
obtained instead of oximes. In the absence of microwave irradiation,
after 15 min grinding of mixture the starting material was recovered
whereas aldehydes give corresponding oximes in the same conditions.[18b]
The general reaction is illustrated according to the Sch. 1 and the results
have been reported in Table 1. All reactions were performed in less than
8 min. As shown in the Table 1 several structurally varied ketones under-
went cleans, remarkably fast and direct nitrogen insertion reactions by a
Beckmann type rearrangement to the corresponding amides. This mild
and versatile method can also be applied for both aromatic and aliphatic
ketones.
Although the mechanism of this transformation is not clear, the first
step is probably the addition–elimination reaction of hydroxylamine
hydrochloride and formation of an oxime-phosphate intermediate. In
the second step, the conversion should take place by the migration of
one of the alkyl or aryl group. Usually one of the isomeric product is
predominate, which is the one that more bulky group has migrates
(Entries 3–6, 8, 9). In the Entry 7 only the methylene migration is
observed. The formation of 2-methyl benzimidazole was reported[19] by
early workers as a result of an intramolecular ring closure in the case of
o-amino acetophenone. However, it was reacted selectively to yield the
corresponding anilide under this condition.
Also ketoximes in the same conditions gave amides by Beckmann
rearrangement. In a typical case, benzophenone oxime and P2O5/SiO2
reagent were mixed together in an Erlenmeyer flask and placed in a
domestic microwave oven and irradiated for 3 min. Benzanilide was
obtained in 95% yield. The general reaction is illustrated according to
the Sch. 2 and the results have been reported in Table 2. As shown in
Table 2 corresponding amides was obtained in 75–95% yields.

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2974
Eshghi and Gordi
Table 1. One-pot preparation of amides from ketones by using P2O5/SiO2 in
solid phase under microwave irradiation.
Yields %
of producta
(isolated)
M.p./ꢀC
found
(lit.)
Time
(min)
Entry
1
Substance
Products
5
100 (88) 68–69 (68–70)[21]
2
3
PhCOPh
PhCOCH3
5
8
PhCONHPh
PhNHCOCH3
PhCONHCH3
100 (95) 164 (163)[20]
85 (70)
15
115 (115–6)[21]
—
4
5
6
PhCOCH2CH3
PhCH2COCH3
PhCH2CH2COCH3
8
3
3
PhNHCOCH2CH3
PhCONHCH2CH3
PhCH2NHCOCH3
PhCH2CONHCH3
75 (65)
25
101–3 (105–6)[20]
—
58–59 (61)[20]
—
70 (63)
30
PhCH2CH2NHCOCH3 75 (68)
PhCH2CH2CONHCH3 25
50–51 (51–52)[21]
—
7
2
98 (75)
231–3 (234–6)[22]
8
9
5
5
98 (95) 130–131 (132)[20]
100 (85) 160–162 (163)[20]
PhCOCOPh
PhCONHCOPh
aIR, 1H-NMR, and m.p. confirmed structures. Ratio of the isomers were
1
determined from H-NMR of the crude mixture.
In conclusion, this new method of nitrogen insertion reactions of
ketones, without preliminarily oxime formation, offers significant
improvements over the excising procedures and thus helps facile
entry into a variety of amides or lactams.[23] Also this simple and readily
available reagent affords various amides in shorter reaction time, with
excellent yields, and good selectivity without involvement of toxic and
expensive material. Further studies of the new applications of P2O5/SiO2
reagentin organic synht esis is in progress.

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Beckmann Type Rearrangement of Ketones
2975
Scheme 2.
Table 2. P2O5/SiO2 mediated Beckmann rearrangement of oximes under
microwave irradiation.
ꢀ
Yields %
of producta
(isolated)b
M.p./ C
found
(lit.)
Entry
1
Substance
Products
100 (85)
68–69 (68–70)[21]
2
3
PhC(NOH)Ph
PhC(NOH)CH3
PhCONHPh
PhNHCOCH3
PhCONHCH3
100 (95)
90 (80)
10
164 (163)[20]
115 (115–6)[21]
4
5
PhCOC(NOH)Ph PhCONHCOPh 98 (85)
98 (75)
160–162 (163)[20]
231–3 (234–6)[22]
aRatio of the isomers was determined from H-NMR of the crude mixture.
bYields refer to isolated pure compounds after column chromatography. IR,
1H-NMR, and m.p. confirmed structures.
1
EXPERIMENTAL SECTION
All melting points recorded are uncorrected open capillary measure-
ments. IR spectra were recorded on a Shimadzu-IR 470 spectrophotom-
eter. 1H-NMR spectra were recorded on a Bruker-80 and 500 MHz
instrument using tetramethylsilane (TMS) as an internal standard.
Silica gel 60 (230–400 mesh) was purchased from Fluka and was dried

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2976
Eshghi and Gordi
ꢀ
in an oven at120 C for 2 h. Irradiation was carried out in a domestic
microwave oven (Electra, 2450 MHz, and 800 W) for optimized time.
Preparation of P2O5/SiO2 reagent. A mixture of phosphorous
pentoxide (6 g) and chromatography grade silica gel (10 g) were placed
in a flask and stirred for 4 h. This homogeneous, free flowing and white
powder reagent is sensitive toward moisture and should be stored in
a dessicator.
General procedure. In a typical reaction, a mixture of ketone
(2 mmol), hydroxylamine hydrochloride (4 mmol) and reagent(1 g)
were grounded thoroughly in a mortar. Usually an immediate color
change was observed. The mortar was covered with a watch glass and
putinside an Elecrta Microwave (2450 MHz, 800 W). The mixut re was
irradiated for the time indicated in Table 1. The completion of the reac-
tion 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 10 mL of 5% aqueous HCl was
added to the mixture. The resulting solution was extracted with CH2Cl2
(2 ꢁ 10 mL). The extracts were combined and dried over CaCl2.
Evaporation of the solvent under vacuum gave amide with high purity
1
(Entries 1, 2, 7–9) (based on TLC, H-NMR, IR and melting point).
Column chromatography or recrystallization from benzene or benzene-
cyclohexane could further purify the products of Entries (3–6).
2-Amino acetanilide was obtained in 95% yield, m.p. 130–131ꢀC
Lit.[20] (132ꢀC). IR (KBr): ꢀ ¼ 3450, 3320, 1640 cmꢂ1
.
1H-NMR
(CDCl3): ꢁ 2.5 (s, 3H), 6.2 (b, 3H), 6.5–6.7 (m, 2H), 7.2 (t, 1H,
J ¼ 8 Hz), 7.7 (dd, 1H, J1 ¼ 8 Hz, J2 ¼ 1.5 Hz).
a-Camphidone was obtained in 75% yield, m.p. 231–233ꢀC Lit.[22]
(234–236ꢀC). IR (KBr): ꢀ ¼ 3200, 1660 cmꢂ1. H-NMR (CDCl3): ꢁ 0.94
1
(s, 3H), 1.03 (s, 3H), 1.08 (s, 3H), 1.58 (m, 1H), 1.76 (m, 1H), 1.89
(m, 1H), 2.05 (m, 2H), 2.97 (d, 1H, J ¼ 9 Hz), 3.47 (dd, 1H,
J1 ¼ 8.5 Hz, J2 ¼ 2 Hz), 5.75 (b, 1H).
N-Benzoyl benzamide was obtained in 85% yield, m.p. 160–162ꢀC
Lit.[20] (163ꢀC). IR (KBr): ꢀ ¼ 3100, 1680 cmꢂ1
.
1H-NMR (CDCl3): ꢁ
7.4–7.7 (m, 6H), 8.1 (dd, 4H, J1 ¼ 8 Hz, J2 ¼ 2 Hz), 11.25 (b, 1H).
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Beckmann Type Rearrangement of Ketones
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Received in the UK July 22, 2002