An efficient and general method for the deoxygenation of organic N-oxides using Zn(OTf)2 and Cu(OTf)2

Article abstract of DOI:10.1055/s-2006-926269

A mild and efficient general method for the deoxygenation of organic N-oxides such as azoxybenzenes, N-arylnitrones, and N-heteroarene N-oxides using Zn(OTf)₂ and Cu(OTf)₂ in excellent yields is described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-926269

LETTER
395
An Efficient and General Method for the Deoxygenation of Organic N-Oxides
Using Zn(OTf)2 and Cu(OTf)2
Deoxygenation of
n
O
rganic
N
-O
i
xides l Saini, Sanjay Kumar, Jagir S. Sandhu*
Department of Chemistry, Punjabi University, Patiala-147 002, India
Fax +91(175)2283073; E-mail: j_sandhu2002@yahoo.com
Received 2 November 2005
they were not environmentally friendly. These already re-
ported procedures include conventional Lewis acids such
as AlI3, TiCl3, and AlCl3, which are neither safe nor
environmentally friendly. They can not be recovered after
the reactions are complete and their waste disposal is also
tedious. With an increasing focus on green methodologies
we report herein a safe and environmentally friendly
procedure for the deoxygenation of organic N-oxides
using Zn(OTf)2 and Cu(OTf)2.
Abstract: A mild and efficient general method for the deoxygen-
ation of organic N-oxides such as azoxybenzenes, N-arylnitrones,
and N-heteroarene N-oxides using Zn(OTf)2 and Cu(OTf)2 in excel-
lent yields is described.
Key words: deoxygenation, metal triflates, nitrones, N-heteroarene
N-oxides, azoxybenzenes
In recent years, metal triflates have attracted considerable
attention.1 This seems to be because of their advantages
over conventional Lewis acids as they can be recovered
and reused. Conventional Lewis acids often leave residues
and their waste disposal is also critical and can cause seri-
ous environmental problems. In contrast, metal triflates
are considered to be environmentally benign and are also Scheme 1
readily accessible2,3 commercially or they can be prepared
in the laboratory and their waste/residues are not at all
Azoxybenzene 1a and Zn(OTf)2 in equimolar amounts,
hazardous. These attractive properties of metal triflates
seems to have encouraged a large amount of research into
their application to C–C bond formation,4 typically aldol,
Mannich, and Reformatsky-type reactions. They have
also been used in cycloaddition reactions,5 oxidations,6 as
well as reductions.7 Our interest in these unconventional
Lewis acids,8 prompted us to investigate the use of metal
triflates such as Zn(OTf)2 and Cu(OTf)2 in the deoxygen-
ation of organic N-oxides, which had previously never
been used for this transformation.
after a reaction time of 70 minutes at 80 °C, furnished
azobenzene 2a in an excellent 82% yield. Similarly, other
azoxybenzenes 1b–d were found to furnish their corre-
sponding azobenzenes 2b–d in excellent yields.
Scheme 2
Organic N-oxides occupy a unique position in synthetic
organic chemistry;9 they are not only excellent dipolar
substrates in cycloaddition reactions,10 they also exhibit
different chemical behavior in comparison to their deoxy-
genated parent nitrogen bases.11 Due to this, selective
deoxygenation of N-oxides has attracted considerable
attention11a and many reagents such as, NaHTe,12 phos-
phorus compunds,13a Al/Ni alloy,13b Ti(0) reagents,14c–14d
silanes,15 TiCl4–NaBH4 complex,16 organotin deriva-
Encouraged by these results, we extended this reagent to
nitrones 3 and N-heteroarene N-oxides 5 and 7. Nitrones
gave their corresponding imines 4 (Scheme 2, Table 1)
and N-heteroarene N-oxides, i.e. pyridine N-oxides 5 and
quinoline N-oxides 7, afforded the deoxygenated products
6 and 8 (Schemes 3 and 4) respectively in quantitative
yields (Table 2).
18
tives,17 InX3 (X = Cl, Br), PCl5, POCl3, SO2Cl2,19 and
The selectivity of the present method is fairly wide, as
several functionalities remain unaffected under these re-
action conditions. Attempts to perform the deoxygenation
very recently another complex system employing
20
MoO2Cl2(dmf)2 have been used. However, several of
these methods have one drawback or another, selectivi-
15,17,22
ty,21 scope,
rigid parameter controls, hazardous
procedure,23 unwanted halogenation of heteroarene
nucleus,19 reduction of aromatic nucleus,16 and sometimes
SYNLETT 2006, No. 3, pp 0395–0398
1
5.
0
2.
2
0
0
6
Advanced online publication: 06.02.2006
DOI: 10.1055/s-2006-926269; Art ID: D33105ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 3

396
A. Saini et al.
LETTER
Table 1 Deoxygenation24 of Azoxybenzenes and Nitrones Using Zn(OTf)2 and Cu(OTf)2
Entry
Producta
2a
R1
R2
Timeb (min)
70 (75)
200 (200)
55 (65)
65 (65)
60 (55)
55 (55)
55 (60)
45 (50)
45 (45)
55 (50)
60 (70)
Yieldb,c (%)
82 (79)
n.r.e
Mpd (°C)
67–68 (68)25
1
2
H
H
2a
H
H
–
3
2b
4-Cl
4-CH3
3-Cl
H
4-Cl
4-CH3
3-Cl
H
86 (78)
82 (87)
78 (76)
74 (77)
81 (80)
78 (72)
79 (76)
81 (83)
80 (74)
187–88 (188)25
143–44 (144)25
103–04 (104)26
51–52 (52)27
4
2c
5
2d
6
4a
7
4b
H
4-Cl
H
61–62 (62)28
8
4c
4-Cl
4-Cl
4-CH3
4-CH3
65–66 (66)29
9
4d
4-Cl
H
110–11(111)30
47–48 (48)30
10
11
4e
4f
4-Cl
112–14 (114)30
a Mps, IR, and 1H NMR spectra were in accordance with those of authentic samples.
b Values in parentheses were obtained using Cu(OTf)2.
c Isolated yields.
d Lit. mp in parentheses.
e No/negligible reaction at r.t.
Table 2 Deoxygenation31 of N-Hetroarene N-Oxides Using Zn(OTf)2 and Cu(OTf)2
Substrate
Product
Reaction time (min)b Yield (%)b,c
Mp/bp (°C)d
115 (115.5)28
60 (65)
65 (65)
89 (80)
87 (79)
6a
129–130 (129–130)28
6b
6c
65 (60)
70 (65)
55 (60)
65 (65)
81 (78)
69 (72)
82 (77)
79 (71)
49–50 (50)28
61–62 (62–63)28
238 (238)28
6d
8a
261 (261)28
8b
a All products were identified by comparison of their IR and 1H NMR spectra with those of authentic samples.
b Values in parentheses were obtained from the reaction using Cu(OTf)2.
c Isolated yields.
d Lit. mp/bp in parentheses.
Synlett 2006, No. 3, 395–398 © Thieme Stuttgart · New York

LETTER
Deoxygenation of Organic N-Oxides
397
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Scheme 4
with less than one equivalent of reagent afforded low
yields but the selectivity remained high. Increasing the
amount of reagent and reaction time did not prove to be
fruitful either, decomposition products were observed. It
is worth mentioning that no deoxygenated product was
obtained when the reaction was carried out at room tem-
perature (Table 1, entry 2). When Zn(OTf)2 is replaced by
Cu(OTf)2 equivalent results were achieved. Also the use
of Sc(OTf)3 in place of Zn(OTf)2 was equally effective but
was not considered for the present study as the reagent is
not water-tolerant. Also the present method is a one-pot
procedure and does not involve any prior preparation of
the reagent system.20
In conclusion, the present protocol is a mild and efficient,
general method employing water tolerant Zn(OTf)2 and
Cu(OTf)2 for the deoxygenation of N-oxides. Excellent
yields, avoiding harsh reagents under mild reaction condi-
tions are the main advantages of this method.
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Acknowledgment
The authors wish to thank the Council of Scientific and Industrial
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Synlett 2006, No. 3, 395–398 © Thieme Stuttgart · New York

398
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mp 52 °C). 1H NMR (200 MHz): d = 8.35 (s, 1 H, CH=N),
7.30–7.60 (m, 10 H, Ar). 13C NMR (50 MHz): d = 122.0,
12.3, 127.0, 128.4, 128.6, 129.0, 129.1, 129.6, 129.8, 130.8,
131.2, 153.2 (Ar), 163.4 (CH).
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(24) Deoxygenation of Nitrones; Typical Procedure
To a stirred solution of benzaldehyde N-phenylnitrone (3a,
0.39 g, 2 mmol) in CH3CN (15 mL) was added Zn(OTf)2 (2
mmol, 1 equiv) and the resulting mixture was stirred at 80 °C
for 70 min. After completion of the reaction (monitored by
TLC), the solvent was removed under reduced pressure, and
the residue was treated with H2O (3 × 30 mL). The resultant
mixture was extracted with CH2Cl2, the organic layer was
To a stirred solution of pyridine N-oxide (5a, 0.19g, 2 mmol)
in CH3CN (15 mL) was added Zn(OTf)2 (2 mmol, 1 equiv)
and the resulting mixture was stirred at 80 °C for 60 min.
The solvent was removed under reduced pressure and H2O
(50 mL) was added. The pH was adjusted to >7 by the
addition of 25% aq NH3 and the product extracted with Et2O
(3 × 50 mL). The organic layer was dried (Na2CO3) and
evaporated to give the crude product, which after
purification afforded pyridine 6a in 89% yield; bp 113–
115 °C (Lit.27 bp 115.5 °C); picrate mp 163–164 °C (Lit.27
mp 164–65 °C). 1H NMR (200 MHz): d = 7.20 (dd, 2 H, J =
8.2 Hz), 7.55 (dd, 1 H, J = 8.2 Hz), 8.50 (d, 2 H, J = 6.2 Hz).
13C NMR (50 MHz): d = 123.2, 123.7, 135.4, 149.6, 149.7.
Synlett 2006, No. 3, 395–398 © Thieme Stuttgart · New York