The beckmann rearrangement executed by visible-light-driven generation of vilsmeier-haack reagent

Article abstract of DOI:10.1055/s-0033-1340623

A new and efficient approach for the Beckmann rearrangement is reported. The protocol involves eosin? Y catalyzed, visible-light-mediated in situ formation of the Vilsmeier-Haack reagent from CBr₄ and a catalytic amount of DMF for activation of ketoximes at room temperature. The method is operationally simple and avoids the need for any corrosive, water-sensitive reagents and elevated temperatures. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340623

LETTER
▌665
lTetthere Beckmann Rearrangement Executed by Visible-Light-Driven Generation
of Vilsmeier–Haack Reagent
Visible-Light-Driven Beckmann Rearrangement
Vishnu P. Srivastava, Arvind K. Yadav, Lal Dhar S. Yadav*
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India
Fax +91(532)2460533; E-mail: ldsyadav@hotmail.com
Received: 20.10.2013; Accepted: 17.12.2013
3
oxidative quenching of EY* has found very limited ap-
Abstract: A new and efficient approach for the Beckmann rear-
rangement is reported. The protocol involves eosin Y catalyzed,
visible-light-mediated in situ formation of the Vilsmeier–Haack re-
6
plication in organic synthesis as compared to its reduc-
4
,7
tive quenching. On the basis of the earlier reports on the
4
agent from CBr and a catalytic amount of DMF for activation of successful application of EY as a photocatalyst coupled
4
ketoximes at room temperature. The method is operationally simple with further exploitation of its oxidative quenching, it has
and avoids the need for any corrosive, water-sensitive reagents and been selected as an organophotoredox catalyst for the
elevated temperatures.
present study.
Key words: visible light, eosin Y, photoredox, Beckmann rear-
The Beckmann rearrangement continues to be a strategi-
rangement, amides
cally useful tool for the synthesis of amides and lactams
from the corresponding oximes since its discovery in
8
1
886. A large amount of strong acids and dehydrating
Nature’s ability to accomplish photosynthesis utilizing
sunlight has inspired the development of a number of syn-
thetically important visible-light-mediated photoredox
catalytic processes. Due to the deleterious effects and side
reactions associated with the use of high-energy UV
agents at an elevated temperature have been traditionally
used to bring about this rearrangement, which leads to
large amount of waste and serious corrosion problems and
precludes its application to sensitive substrates. In order to
make the rearrangement economically and environmen-
tally viable, several methods have been recently devel-
1
light, visible-light-mediated photoredox catalysis has
emerged as a new technique for developing new method-
9
oped and claimed to be organocatalytic. Very recently,
ologies. MacMillan2 and Yoon groups have demon-
a
2b
these methods have been a subject of ingenious discussion
on the point whether they are actually organocatalytic or
strated that the use of photocatalysts such as Ru(bpy) Cl
3
2
(
bpy = 2,2′-bipyridine) and Ir(dtbbpy) Cl (dtbbpy = 4,4′-
10
3
merely self-propagating. Thus, there is still a wide scope
di-tert-butyl-2,2′-bipyridine) is capable of initiating pow-
for investigations on convenient and more rational meth-
ods to execute the Beckmann rearrangement.
erful transformations, both for the target-oriented organic
2
synthesis and methodology development. Very recently,
After careful consideration of the above facts and our con-
tinued efforts for the development of new organocatalytic
Stephenson et al. have opened a new opportunity for the
activation of hydroxyl functionality employing a visible-
7
c,9c,d,11
3
processes,
we sought to explore and establish an ef-
light-mediated photocatalytic process. The resulting
3
a
ficient and operationally simple Beckmann rearrange-
ment. The present novel design of the Beckmann
rearrangement is inspired by the recent work of Stephen-
transformation of alcohols to halides or carboxylic acids
3
b
to anhydrides proceeds through the oxidative quenching
2
+
of the excited organometallic catalyst Ru(bpy) to pro-
3
3
vide the strong oxidant Ru(bpy)23
+
.
son et al. and it utilizes EY as a photocatalyst instead of
Ru(bpy) Cl (Scheme 1). An in situ generated Vilsmeier–
3
2
However, the utilization of ruthenium and iridium com-
plexes suffers from disadvantages such as potential toxic-
ity, low sustainability, high cost, and problematic removal
of their undesirable traces from products, especially in the
case of drugs and drug intermediates. Recently, metal-free
organic dyes have shown enough promise for their appli-
cation as photocatalysts in visible-light-mediated photore-
dox reactions4 and offer a superior alternative to
transition-metal photocatalysts because they are inexpen-
sive, easy to handle, and eco-friendly. It has been reported
Haack reagent from DMF is a well-studied species for ef-
fecting the Beckmann rearrangement in a stoichiometric
amount, thus we envisaged that the rearrangement could
be rendered catalytic with respect to DMF. After some
preliminary experimentation, we were able to realize that
the present visible-light-driven Beckmann rearrangement
could be effected through the Vilsmeier–Haack reagent
with a catalytic amount of DMF.
The Beckmann rearrangement of a model substrate 4-me-
thoxyacetophenone oxime (1a) was performed by using
2
+
that similar to the chemistry of Ru * (* = excited state)
both reductive and oxidative quenching are known for the
EY as a photocatalyst, CBr as an oxidative quencher, and
4
3
5
a catalytic amount of DMF in MeCN under irradiation
with visible light for the screening process (Table 1).
Among the different light sources used, viz. green LEDs
excited triplet state EY* of eosin Y (EY). However, the
SYNLETT 2014, 25, 0665–0670
Advanced online publication: 15.01.2014
(light-emitting diodes, λmax = 535 nm, 2.6 W, 161 lm),
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
CFL (18 W), and daylight, green LEDs were found to be
DOI: 10.1055/s-0033-1340623; Art ID: ST-2013-D0983-L
Georg Thieme Verlag Stuttgart · New York
©

666
V. P. Srivastava et al.
LETTER
Next, we optimized reaction conditions with respect to
catalyst loading and solvent (Table 2). The yield was sig-
nificantly decreased with decreasing eosin Y from 2
mol% to 1 mol% (Table 2, entry 2 vs. 3); whilst it was not
affected by increasing the catalyst loading from 2 mol% to
OH
X
R
R
R
R
ref. 3a (X = Br, I)
O
(
SN reaction)
Me
H
Me
Br
N
O
O
5
mol% (Table 2, entry 1 vs. 2). Thus, the optimum cata-
CBr4, visible light
photocatalyst, r.t.
R
OH
ref. 3b
lyst loading of eosin Y was found to be 2 mol%. The op-
timum catalytic amount of DMF was found to be 20
mol%, because decreasing its amount from 30 mol% to 20
mol% did not affect the yield (Table 2, entry 2 vs. 4);
whilst decreasing the amount from 20 mol% to 15 mol%
significantly decreased the yield (Table 2, entry 4 vs. 5).
Under the optimized catalyst loading different solvent
media were tested, and among all the tested solvents
R
(
O
R
dehydration)
Vilsmeier–Haack
reagent
OH
O
N
Me
O
H
N
R1
R2
R1
R2
Me
N
(
this work)
H
(
rearrangement)
Scheme 1 Visible-light-mediated activation of hydroxyl groups
(
MeCN, DCE, THF, and MeNO ), MeCN was the best
2
(
Table 2, entry 4). The highest yield (96%) was obtained
the best in terms of yield and reaction time (Table 1, en-
tries 1–5 vs 6 and 7). This result encouraged us to carry
out a series of control experiments (Table 1), which indi-
cated that in the absence of any of the reagents/reaction
parameters, no product formation was detected (Table 1,
entries 8–11).
in the case of MeCN (Table 2), hence it was used as sol-
vent throughout the present study.
Table 2 Optimization of Catalyst Loading and Solventa,b
eosin Y, DMF
solvent, CBr4
N
OH
MeO
MeO
NH
O
green LEDs
r.t., 14–20 h
Table 1 Screening and Control Experiments for the Visible-Light-
2a
Driven Beckmann Rearrangementa
Entry
Eosin Y
(mol%)
DMF
(mol%)
Solvent
Time
(h)
Yield
(%)c
eosin Y, DMF
MeCN, CBr4
N
OH
MeO
MeO
NH
O
visible light
r.t., 10–48 h
1
2
3
4
5
6
7
5
2
1
2
2
2
2
2
30
30
30
20
15
20
20
20
MeCN
MeCN
MeCN
MeCN
MeCN
DCE
14
14
14
14
14
18
20
15
96
96
67
96
71
76
60
78
1
a
Entry Visible light
Eosin Y CBr4
DMF Time Yield
b
(
mol%) (equiv) (mol%) (h)
(%)
1
2
3
4
5
6
7
8
9
0
1
green LEDc
green LED
green LED
green LED
green LED
2
2
2
2
2
2
2
0
2
2
5
3
2
1
1
2
2
2
2
0
2
2
20
20
20
20
20
20
20
20
20
0
14
14
18
30
10
48
48
48
48
48
48
96
96
58d
58d
85
THF
8
MeNO2
a
The reaction was carried out with 1a (1.0 mmol) and CBr (2.0
4
CFL (18 W)e
mmol) in solvent (3 mL) under a nitrogen atmosphere for each entry.
39
b
Green LEDs 2.6 W, 161 lm (for details, see the Supporting Informa-
daylight
24
tion) were used for irradiation at 2 cm distance from the reaction mix-
ture with its temperature not exceeding to 25 °C.
green LED
green LED
green LED
in the dark
n.r.
n.r.
n.r.
n.r.
c
Isolated yield after aqueous workup followed by column chromatog-
raphy.
1
With the optimized reaction conditions in hand, the func-
tional-group compatibility and scope of the present photo-
catalytic protocol were demonstrated across a range of
aromatic, aliphatic acyclic, and aliphatic cyclic oximes
1
20
a
The reaction was conducted with 1a (1.0 mmol) in MeCN (3 mL) un-
der a nitrogen atmosphere for each entry.
b
Isolated yield after aqueous workup followed by column chromatog- (Table 3). The presence of an electron-withdrawing group
raphy; n.r. = no reaction.
Green LEDs 2.6 W, 161 lm (for details, see the Supporting Informa-
tion) were used for irradiation at 2 cm distance from the reaction mix-
in the aryl moiety of an oxime appears to decrease the
yield (Table 3, entry 3 vs. entries 6–10), while the yield is
enhanced in case of the presence of an electron-donating
group (Table 3, entry 3 vs. entries 1, 2, 4, and 5). A variety
c
ture with its temperature not exceeding to 25 °C.
d
3
7% of 1a was recovered.
e
of functional groups such as OMe, OH, Br, and NO are
1
8 W CFL (compact fluorescent lamp, Philips, 6500 K, 1010 lm, 85
2
mA) was used for irradiation.
compatible with the present protocol for the Beckmann re-
Synlett 2014, 25, 665–670
© Georg Thieme Verlag Stuttgart · New York

LETTER
Visible-Light-Driven Beckmann Rearrangement
667
12
arrangement. The industrially important ε-caprolactam DMF to generate 4 as reported earlier. Aqueous workup
could also be obtained in good yield (Table 3, entry 13).
of the reaction mixture containing 7 gives the desired
product 2. As mentioned in Table 1 (entries 3 and 4), the
yield of Beckmann rearrangement product 2a was drasti-
On the basis of our observations and the literature re-
ports,3–7 a plausible pathway for the conversion of 1 into
cally reduced on decreasing the amount of CBr from two
4
2
through the Beckmann rearrangement is depicted in
equivalents to one equivalent, that is, on decreasing the
amount of 6, which generates the Vilsmeier–Haack re-
agent 4 and the intermediate 3 leading to the product 2.
This shows that the rearrangement is not self-propagating
instead it is catalytic with respect to DMF, as depicted in
Scheme 2. Had the reaction been self-propagating, it
would have not proceeded to give the yield of only 58%
with the recovery of 37% of oxime 1a (Table 1, entries 2
vs. 3 and 4). Furthermore, DMF could be recovered up to
Scheme 2. The photoredox catalyst EY is excited on ab-
sorption of visible light, and its more stable triplet state
3
EY* undergoes oxidative quenching by single-electron
•
transfer (SET) to CBr and generates CBr , which reacts
4
3
with DMF to form radical 5. Then, SET from the radical
•
+
5
to EY gives iminium ion 6 to complete the redox cycle.
Iminium ion 6 is converted into Vilsmeier–Haack reagent
, which reacts with the hydroxyl group of oxime 1 to
4
form imidoyl bromide 7 through 3. Furthermore, COBr2
formed as a byproduct in the reaction pathway reacts with
94% after the reaction.
Table 3 Generality and Scope of the Visible-Light-Driven Beckmann Rearrangementa
R1
O
eosin Y (2 mol%), DMF (20 mol%), CBr4 (2.0 equiv)
MeCN, green LEDs, r.t., 12–18 h
R1
N
R2
N
R2
OH
H
1
2
Entry
1
Ketoxime 1
Product 2
Time (h)
14
Yield (%)b,c
MeO
NH
O
N
OH
MeO
96
2
2
2
a
b
c
H
N
N
OH
2
3
4
5
14
14
14
14
93
90
96
92
O
H
N
N
OH
O
H
N
N
OH
HO
O
HO
2
d
H
MeO
MeO
N
N
OH
O
2
e
f
Br
H
N
Br
N
OH
6
7
14
16
84
86
O
2
H
N
N
OH
Br
O
Br
2
g
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 665–670

668
V. P. Srivastava et al.
LETTER
a
Table 3 Generality and Scope of the Visible-Light-Driven Beckmann Rearrangement (continued)
R1
O
eosin Y (2 mol%), DMF (20 mol%), CBr4 (2.0 equiv)
MeCN, green LEDs, r.t., 12–18 h
R1
N
R2
N
R2
OH
H
1
2
Entry
8
Ketoxime 1
Product 2
Time (h)
18
Yield (%)b,c
H
N
N
OH
80
O2N
O
O
O2N
2
h
H
N
N
OH
2
O N
9
18
18
85
77
O2N
2
i
OH
H
N
N
1
0
1
O
NO2
NO2
2
2
2
2
j
OH
H
N
N
1
14
14
12
85
84
78
O
k
O
N
H
1
2
3
N
OH
l
O
NH
N
1
OH
m
N
O
OH
14
NH
12
89
2
2
n
o
O
OH
N
N
H
1
5
6
12
16
88
91
OH
H
N
N
1
O
2
p
a
Reaction conditions: 1 (1.0 mmol); eosin Y (2 mol%); CBr (2.0 equiv), DMF (20 mol%) in MeCN (3 mL), irradiation with green LEDs under
4
1
3
a nitrogen atmosphere.
b
Isolated yield after aqueous workup followed by column chromatography.
For the characterization data of compounds 2, see the Supporting Information.
c
Synlett 2014, 25, 665–670
© Georg Thieme Verlag Stuttgart · New York

LETTER
Visible-Light-Driven Beckmann Rearrangement
669
Scheme 2 Plausible mechanistic pathway of visible-light-driven Beckmann rearrangement
In conclusion, we have disclosed an efficient Beckmann
rearrangement involving activation of ketoximes by the
Vilsmeier–Haack reagent, which is in situ generated by an
eosin Y catalyzed, visible-light-driven reaction of CBr4
and a catalytic amount of DMF in MeCN at room temper-
ature. This operationally simple protocol offers a superior
alternative to the existing methods because it avoids the
need for corrosive, water-sensitive reagents and elevated
temperatures. Moreover, the rearrangement is catalytic
with respect to DMF and it is not self-propagating.
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2
012, 134, 2958. (b) Xiao, T.; Dong, X.; Tang, Y.; Zhou, L.
We sincerely thank the SAIF, Punjab University, Chandigarh, for
providing spectra. V.P.S. is grateful to the Department of Science
and Technology (DST) Govt. of India, for the award of a DST-In-
spire Faculty position (Ref. IFA-11CH-08) and financial support.
A.K.Y. is grateful to the CSIR, New Delhi, for the award of a Junior
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m
iotSrat
n
ungIifoop
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t
(
2
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©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 665–670

6
70
V. P. Srivastava et al.
LETTER
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7
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(
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4
(
1
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