Conversion of piperidine-4-ones into [1,4]-diazepan-5-ones under microwave irradiation using a silica gel supported NaHSO4, catalyst

Article abstract of DOI:10.3184/030823407X198276

A rapid conversion of some 2,6-diarylpiperidin-4-ones into 2,7-diaryl-[1,4]-diazepan-5-ones in high yields has been developed involving treatment with hydroxylamine hydrochloride under microwave irradiation in the presence of a silica gel supported NaHSO₄ catalyst.

Full text of DOI:10.3184/030823407X198276

80 RESEARCH PAPER
FEBRuARy, 80–81
JOuRNAL OF CHEMICAL RESEARCH 2007
Conversion of piperidine-4-ones into [1,4]-diazepan-5-ones under
microwave irradiation using a silica gel supported NaHSO4 catalyst
M. Gopalakrishnan*, P. Suresh Kumar, J.Thanusu, C. Prabhu and V. Kanagarajan
Department of Chemistry, Annamalai University, Annamalainagar – 608 002, Tamil Nadu, India
A rapid conversion of some 2,6-diarylpiperidin-4-ones into 2,7-diaryl-[1,4]-diazepan-5-ones in high yields has been
developed involving treatment with hydroxylamine hydrochloride under microwave irradiation in the presence of a
silica gel supported NaHSO4 catalyst.
Keywords: [1,4]-diazepan-5-ones, silica gel supported NaHSO4 catalyst, solvent-free conditions, microwave irradiation,
environmentally friendly
During the last decade, a number of publications and
reviews1-9 have advocated the use of microwave technology
in organic synthesis. With no direct contact between the
chemical reactants and the energy source, microwave-assisted
chemistry can be more efficient in terms of the energy used,
provide faster heating rates and enable rapid optimisation of
synthetic procedures, often with an increase in reaction rate
and efficiency.
The conversion of ketones into the corresponding amides
is an important transformation that has been utilised for
the synthesis of various bioactive natural compounds10 as
well as for the industrial production of polyamides, such as
nylon-6.11 The ketones can be converted into oximes, which
undergo Beckmann rearrangement to produce amides.12
One-pot conversion of ketones into amides (e.g., Schmidt
rearrangement) has also been reported,13 though numbers
are limited. However, these methods suffer from certain
drawbacks, which include the use of corrosive reagents
(e.g., nitroparaffin and concentrated H2SO4, NaN3 and
concentrated H2SO4, hydroxylamine-o-sulfonic acid, etc.),
low yields and several steps involved in the experimental
procedure. The process using concentrated H2SO4 may
affect systems that are sensitive to acids.14a-c Moreover, these
methods, which have not utilised microwave irradiation
require long reaction times.13,14
Results and discussion
3-Alkyl-2,7-diaryl-[1,4]-diazepan-5-ones
(3),
seven
membered lactams, which are intermediates in 1,2-diamines
synthesis15 have been formed by Beckmann and Schmidt16
rearrangements from piperidin-4-ones (1). However, these
two methods suffer from some drawbacks like longer reaction
periods, low yields, tiresome workup procedure and use of
corrosive concentrated H2SO4 and polyphosphoric acid.
Das et al.17 reported the conversion of ketones to amides
using NaHSO4.SiO2 catalyst under microwave irradiation.
We have now adopted this method for the formation of 3-
alkyl-2,7-diaryl-[1,4]-diazepan-5-ones (3a–g) from 2,6-
diphenylpiperidin-4-ones (1a–g) (Scheme 1).
The oximes are believed to be intermediates in this
reaction, but we are unable to isolate the respective oximes.
To confirm the formation of oximes as intermediates, we ran the
reaction with respective oximes and the NaHSO4.SiO2 catalyst
under microwave irradiation at P = 160W. As we expected,
the oximes gave the 3-alkyl-2,7-diaryl-[1,4]-diazepan-5-ones
1
quantitatively. In all cases, H NMR spectroscopic studies
revealed that the migration is preferentially anti.
In summary, microwave-assisted solvent-free (under
conditions of so-called ‘green chemistry’) reactions were
employed to synthesise 3-alkyl-2,7-diaryl-[1,4]-diazepan-5-
ones in good to excellent yields. The method not only offers
a substantial improvement in yield over conventional heating
O
O
R2
R1
OHC
R2
R1
+
Ethanol
CHO
N
H
(1a-g)
+
NH4
-O
X
X
X
X
O
NH2 OH.HCl
NaHSO4.SiO2
MW, 160W
2-5 min
R1 = H, CH 3, C2H5, CH(CH 3)2, (CH3)2
R2 = H, CH 3
X = H, o-Cl
HO
O
H
N
N
R1
R2
R1
R2
N
H
N
H
X
X
X
(3a-g)
X
(2a-g)
Scheme 1 A convenient synthesis of some novel [1,4]-diazepan-5-ones (3a–g).
* Correspondent. E-mail: emgeekk@yahoo.co.in
PAPER: 06/4228

JOuRNAL OF CHEMICAL RESEARCH 2007 81
Table 1 Synthesis of [1,4]-diazepan-5-ones under microwave irradiation
Entry R1
R2
X
Reaction Yield
M.p./°C
Elemental analysis (%)
time/min
/%
Carbon
found
(calculated)
Hydrogen
found
(calculated)
Nitrogen
found
(calculated)
3a
3b
3c
3d
3e
3f
H
H
H
H
H
H
2
2
2
2
2
3
5
90
95
85
90
95
85
85
168–170 (170)
183–185 (183)
187–189 (188)
186–188 (188)
177–179 (180)
209–211
76.5 (76.66)
77.0 (77.11)
77.5 (77.52)
77.8 (77.89)
77.5 (77.52)
60.9 (60.91)
61.9 (61.90)
6.8 (6.81)
7.1 (7.19)
7.5 (7.53)
7.8 (7.84)
7.5 (7.53)
4.8 (4.81)
5.1 (5.19)
10.6 (10.52)
9.9 (9.99)
9.5 (9.52)
9.1 (9.08)
9.5 (9.52)
8.3 (8.36)
8.0 (8.02)
CH3
C2H5
i-Pr
H3C
H
H
H
H
H3C
H
H
H
o-Cl
o-Cl
3g
H3C
201–203
*Melting points given in parentheses are from ref. 16.
3,6-Dimethyl-2,7-diaryl-[1,4]-diazepan-5-one(3e):IR(KBr)(cm-1):
3446, 3333, 3081, 2979, 2934, 2821, 1661; MS (m/z): 295 M+. (M.F.
C19H22N2O); 1H NMR (δ ppm): 0.72–0.82 (d, 6H, CH3), 2.08 (s, 1H,
H1), 3.10 (m, 1H, H6e), 3.89 (m, 1H, H3a), 3.66 (d, 2H, H2), 3.80
(d, 2H, H7), 5.69 (s, 1H, H4), 7.21–7.38 (m, 10H, aryl protons).
2,7-Bis(2-chloro-phenyl)-[1,4]-diazepan-5-one(3f):IR(KBr)(cm-1):
3449, 3316, 3089, 2932, 2798, 1675; MS (m/z): 336 (M+.) (M.F.
C17H16Cl2N2O); H NMR (δ ppm): 2.18 (s, 1H, H1), 2.70 (d, 1H,
H6e), 3.28 (m, 2H, H3e and H6a), 3.81 (m, 1H, H3a), 4.59 (d, 2H, H2),
4.70 (d, 2H, H7), 6.21 (s, 1H, H4), 7.40–7.81 (m, 8H, aryl protons).
methods but also eliminates the use of hazardous solvents
and an excess of expensive acidic catalyst. Advantages of this
method include the fact that it is environmentally friendly,
is an economical procedure, has a short reaction time and has
simplicity of performance with non-aqueous work-up.
1
Experimental
General remarks
Extent of reaction and the purity of the products was assessed by TLC.
All the reported melting points were taken in open capillaries and are
uncorrected. IR spectra were recorded in KBr (pellets) on a Nicolet-
Avatar–360 FT-IR spectrophotometer and noteworthy absorption
values (reciprocal centimetre) alone are listed. 1H NMR spectra were
recorded at 300 MHz on a Bruker AV 300 spectrometer using CDCl3
as solvent and TMS as internal standard. The APCI +ve mass spectra
were recorded on a Shimazdu LCMS-QP8000α LC MS spectrometer.
Elemental analysis was carried out using a PERKIN ELMER-240
CHN analyser. A conventional (unmodified) domestic microwave
oven equipped with a turntable (LG, MG-395 WA, 230V~50 Hz,
760 W) was used for the irradiation. 2,6-Diarylpiperidin-4-ones
were prepared by a literature method.18 NaHSO4.SiO2 catalyst was
prepared by the literature method.19
2,7-Bis(2-chloro-phenyl)-3-methyl[1,4]-diazepan-5-one
(3g):
IR (KBr) (cm-1): 3308, 3212, 3087, 2928, 2885, 2857, 1669; MS (m/z):
350 M+. (M.F. C18H18Cl2N2O); 1H NMR (δ ppm): 0.95 (d, 3H, CH3),
2.17 (s, 1H, H1), 2.71 (d, 1H, H6e), 3.22 (t, 1H, H6a), 3.92 (m, 1H,
H3a), 4.51 (d, 2H, H2), 4.72 (d, 2H, H7), 5.89 (s, 1H, H4), 7.41–7.70
(m, 8H, aryl protons).
Received 30 September 2009; accepted 23 January 2007
Paper 06/4228
doi:10.3184/030823407X198276
References
1
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Experimental method for the preparation of 2,7-diphenyl-[1,4]-
diazepan-5-one (3a)
2
3
4
5
6
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In a 100 ml borosil beaker, 2,6-diphenylpiperidin-4-one (0.1 mol) and
NH2OH.HCl (0.3 mmol) were mixed thoroughly with NaHSO4.SiO2
catalyst (100 mg), and the mixture was placed inside a microwave
oven and irradiated for 2 min. The mixture was removed from the
oven, cooled and shaken with ethyl acetate (40 ml). The catalyst was
removed by filtration. The filtrate was concentrated and the residue
was subjected to column chromatography over silica gel using
ethylacetate: petroleum ether (40:60) (0.2:0.8) as eluent to afford
the corresponding product (3a) as a crystalline solid. IR (KBr) (cm-
1): 3447, 3311, 3082, 2927, 2792, 1671; MS (m/z): 267 (M+.) (M.F.
7
8
9
1
(a) S. Galema, Chem. Soc. Rev., 1997, 26, 233; (b) F. Langa, P. de la Cruz,
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C17H18N2O); H NMR (δ ppm): 2.11 (s, 1H, H1), 2.67 (d, 1H, H6e),
3.17 (m, 2H, H3e and H6a), 3.70 (m, 1H, H3a), 4.03 (d, 2H, H2), 4.14
(d, 2H, H7), 6.16 (s, 1H, H4), 7.26–7.45 (m, 10H, aryl protons).
Compounds 3b–g were synthesised similarly and further details
for 3a–g are given in the Table.
10 K. Marouka and H. yamamoto, Comprehensive Org. Synth., B.M. Trost,
Ed, Pergamon Press, 1991, 6, 763.
11 (a) G.A. Olah and A.P. Fung, Synthesis, 1979, 537; (b) R.E. Gawley, Org.
React., 1988, 35, 1.
3-Methyl-2,7-diaryl-[1,4]-diazepan-5-one (3b): IR (KBr) (cm-1):
3302, 3207, 3082, 2925, 2880, 2852, 1667; MS (m/z): 281 M+.
(M.F. C18H20N2O); 1H NMR (δ ppm): 0.75 (d, 3H, CH3), 2.07 (s, 1H,
H1), 2.65 (d, 1H, H6e), 3.15 (t, 1H, H6a), 3.82 (m, 1H, H3a), 3.70 (d,
2H, H2), 4.13 (d, 2H, H7), 5.82 (s, 1H, H4), 7.26–7.38 (m, 10H, aryl
protons).
12 (a) H.M. Meshram, Synth. Commun., 1990, 20, 3253 and references
cited therein; (b) A.I. Bosch, P. De la Cruz, E. Diez-Barra, A. Loupy and
F. Langa, Synlett, 1995, 1295 and references cited therein.
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6668); (c) C. Barnet, I.M. Cohn, J. Lincoln, U.S. Patent, 1956, 2754298
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19 B. Gary and W. Breton, J. Org. Chem., 1997, 62, 8952.
3-Ethyl-2,7-diaryl-[1,4]-diazepan-5-one (3c): IR (KBr) (cm-1):
3308, 3224, 3061, 2978, 2929, 2881, 2852, 1663; MS (m/z): 295 M+.
1
(M.F. C19H22N2O); H NMR (δ ppm): 0.85 (t, 3H, CH3), 1.11 (m,
2H, CH2), 2.03 (s, 1H, H1), 2.65 (d, 1H, H6e), 3.14 (t, 1H, H6a), 3.65
(m, 1H, H3a), 3.77 (d, 2H, H2), 4.13 (d, 2H, H7), 5.76 (s, 1H, H4),
7.21–7.42 (m, 10H, aryl protons).
3-Isopropyl-2,7-diaryl-[1,4]-diazepan-5-one (3d): IR (KBr) (cm-1):
3590, 3399, 3060, 2972, 2847, 2840, 2837, 1650; MS (m/z): 309
1
M+. (M.F. C20H24N2O); H NMR (δ ppm): 0.95 (d, 6H, CH3), 1.60
(m, 1H, CH), 2.07 (s, 1H, H1), 2.64 (d, 1H, H6e), 3.16 (t, 1H, H6a),
3.61 (m, 1H, H3a), 3.95 (d, 2H, H2), 4.10 (d, 2H, H7), 5.74 (s, 1H,
H4), 7.28–7.45 (m, 10H, aryl protons).
PAPER: 06/4228