Fe-Catalyzed tandem cyclization for the synthesis of 3-nitrofurans from homopropargylic alcohols and Al(NO3)3·9H2O

Article abstract of DOI:10.1039/c8ob01184b

Al(NO₃)₃·9H₂O as a nitro source for the synthesis of 3-nitrofurans from homopropargylic alcohols through Fe-catalyzed tandem cyclization is described. In this transformation, the substituted nitrofurans are obtained throug

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Fe-Catalyzed Tandem Cyclization for the Synthesis of 3-
Nitrofurans from Homopropargylic Alcohols and Al(NO3)3·9H2O
Ting Wang,a Yong Jiang,b Yanyan Wang,c Rulong Yan*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
zhang's work:
Al(NO3)3·9H2O as the nitro source for the synthesis of 3-
nitrofurans from homopropargylic alcohols through Fe-
catalyzed tandem cyclization is described. In this
transforamtion, the substituted nitrofurans are obtained
through nitration and cyclization. The substrate
homopropargylic alcohols with different groups proceeded
smoothly in this process and the desired substituted
nitrofurans are obtained in moderate yields.
O
X
Cu(OAc)2 (0.2 equiv.)
O
X
R
R
(NH4)2Ce(NO3)6 (2.0 equiv.)
R, R'=alkyl, aryl
X=C, N, O
R'
DCE, 80 o
C
NO2
R'
our previous work:
I2 (10 mol %)
TBHP (2.0 equiv.)
SMe
R2
OH
OH
R2
DMSO
R1
R1
NH4I (2.0 equiv.), 150 o
C
O
Nitro-containing compounds are widely used as high-energy
materials, dyes, pharmaceuticals, perfumes and plastics.1
Among them, the nitrofuran derivatives are widely used as
building pharmaceutical and biologically active molecules.2 For
example, nitrofurazone and nitrofurantoin (NFZ and NFT) are
widely used to against common infections.3
R1
S
R3
R3
OH
I2
R1SO2NHNH2
R2
R2
S
R2
R3
O
R1
I
This work:
The methods of synthesize nitro compounds have received
great attentions in organic chemical synthesis. Classical
nitration of C-C bonds and C-hetero bonds have been
significantly developed and the approaches are mainly
including the strategies of electrophilic substitution using
NO2
Ar2
FeCl3 (20 mol %)
CH3CN, 80 oC, 2 h
OH
R1
Al(NO3)3
9H2O
Ar2
R1
O
Scheme 1. Previous works
+
nitronium cation4 (NO2 ) and nucleophilic substitution with
-
nitrite anion5 (NO2 ). In the recent years, tert-butyl nitrite (TBN)
readily available. Zhang’s group reported a challenging method
about copper-assisted direct nitration of cyclic ketones with
ceric ammonium nitrate (CAN) (scheme 1).9 The group of
Zhang also reported an elegant approach about meta-selective
C–H nitration of arenes with Cu(NO3)2·3H2O.10 However, most
of reports about nitration are focused on introducing nitro
group to arene,11 alkene or alkane and there is less research
on the tandem cyclization to construct nitro-containing
heterocyclic compounds.
as model nitration reagent for introducing nitro group has
been well exploited. The groups of Maiti6 and Prabhu7 have
made great contributions on the synthesis of substituted
nitroolefins with TBN. Despite the great applications of TBN in
nitration, obvious drawbacks of TBN are highly exothermic
decomposition at elevated temperatures and potential
hazardous.8 Recently, the efficient metal-catalyzed nitration
with nitrates have been well developed. The outstanding
features of nitrates as the nitro source are inexpensive and
The most common methods for the synthesis of the nitro
furans are mainly concentrated on the direct nitration of furan
with highly acidic reaction conditions (HNO3).12 So the
synthesis of 3-nitrofuran is still highly desirable and also
remains great challenge. Our group had developed several
methods to synthesize methylthiofurans and sulfanylfurans
from homopropargylic alcohols through tandem cyclization
reaction (scheme 1).13 Inspired by the works of utilization
nitrates and our experiences in construction substituted furans
a
State Key Laboratory of Applied Organic Chemistry, Key laboratory of Nonferrous
Metal Chemistry and Resources Utilization of Gansu Province, Department of
Chemistry, Lanzhou University, Lanzhou, Gansu, China.
Fax: 0931-8912596 E-mail: yanrl@lzu.edu.cn
b
School of Chemistry and Chemical Engineering, Yangtze Normal University,
Chongqing, China.
c Jinchuan Advanced Materials Technology Co., Ltd. Lanzhou, Gansu, China.
† Electronic Supplementary Information (ESI) available: Experimental procedures
spectroscopic data.. See DOI: 10.1039/c000000x/
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Table 1. Optimization of reaction conditions a
Scheme 2. Scope of substituted homopropargylic alcohols
NO2 source
Yield
(%)b
55
Entry
Solvent Catalyst Temp(℃)
(X equiv.)
1
2
Fe(NO3)3·9H2O
Cu(NO3)3·3H2O
Bi(NO3)3·5H2O
NH4Ce(NO3)6
Al(NO3)3·9H2O
Al(NO3)3·9H2O
Al(NO3)3·9H2O
Al(NO3)3·9H2O
Al(NO3)3·9H2O
Al(NO3)3·9H2O
Al(NO3)3·9H2O
Al(NO3)3·9H2O
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
BF3·Et2O
Tf2O
80
80
80
80
60
80
120
80
80
80
80
80
80
80
80
43
3
Trace
30
4
5
6c
55
60
7
53
8
65
9
54
10
11
12
13
14
15
55
CuCl
46
FeCl3
FeCl3
FeCl3
FeCl3
17
Al(NO3)3·9H2O CH3NO2
26
Al(NO3)3·9H2O
Al(NO3)3·9H2O
C6H5Cl
THF
26
24
a Reaction conditions: 1a (0.2 mmol), NO2 sources (0.1 mmol), catalyst
(20 mol %), solvent (2 mL), 80 ℃. b Yields of isolated products. c Under
nitrogen. DMF = N,N-Dimethylformamide, Tf2O
= Trifluoromethane
sulfonic anhydride.
through tandem cyclization, herein, we reported
a
straightforward method to synthesize 3-nitrofuran with
homopropargylic alcohols and aluminum nitrate nonahydrate
under mild condition. (Scheme 1).
Our investigation was commenced firstly with the 1,4
diphenylbut-3-yn-1-ol
nitration agent and 20 mol % of FeCl3 as catalyst in acetonitrile
(MeCN) at 80 under air. The desired product 3-nitro-2,5-
(1a) as substrate, Fe(NO3)3·9H2O as
℃
diphenylfuran (3a) was isolated in 55% yield (table 1, entry 1).
A series of metal nitro compounds, such as Al(NO3)3·9H2O,
Bi(NO3)3·5H2O, Fe(NO3)3·9H2O, Cu(NO3)3·3H2O and NH4Ce(NO3)6
were also evaluated for this reaction and the Al(NO3)3·9H2O
was found as the most effective nitro source for this process
and the yield was increased to 65% (Table1, entries 1-5 ).
Further, various solvents were also screened and the
acetonitrile was the most efficient solvent for this
transformation and the isolated 3a was obtained in 65% yield
(Table 1, entry 8 and entries 12-15). The employment of FeCl3
nitro furans in moderate yields. The optimized conditions were
consistent with various homopropargylic alcohols with
electron-donating substituents Me, diMe, and OMe groups on
the aryl ring. Fluorine-containing derivatives of homopropargylic
alcohols could also tolerated in this transformation, giving the
corresponding products 3h and 3i with moderate yields. The
substrates 1j and 1q with Cl group could not work under the
optimized conditions and only trace amount of desired
products was detected. In addition, the homopropargylic
as catalysts gave a better yield than BF3·Et2O，Tf2O and CuCl
(Table 1, entries 8-11). When the dose of AcOH was changed
to 20 mol %, the yield was afforded in 88%. The result of
changing temperature revealed that there was no effect on
the yield (Table 1, entries 5 and 7). So the optimized conditions
were established as shown in Table 1, entry 8.
W
e next examined the substrate scope of homopropargylic
alcohols 1k, 1l and 1t with thienyl or naphthyl group also can
alcohols under the optimized conditions in hand. As illustrated
in Scheme 2, a series of homopropargylic alcohols with
electron-donating or withdrawing groups on benzene rings
perform well in this transformation and the desired product 3k
3l and 3t were isolated in 60%, 45% and 35% yields. Further
investigation disclosed that the alkyl groups on
,
reacted with substrate 2 smoothly, generating the desired
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Scheme 3. Control experiments
In summary, we have developed a straightforward method
for the synthesis of 3-nitrofurans with homopropargylic
alcohols and aluminum nitrate nonahydrate, affording the
substituted nitro furans in moderate yields. This method
constitutes a concise access to nitrofurans through radical
nitration and tandem intermolecular cyclization. Using
nontoxic and inexpensive Al(NO3)3·9H2O as the nitro source is
another notable feature. Therefore, this reaction will provide a
practical method for the synthesis of nitro compounds.
This work was supported by National Natural Science Foundation
of China (21672086), Gansu Province Science Foundation for Youths
(1606RJYA260) and the Fundamental Research Funds for the
Central Universities (lzujbky-2018-81).
Notes and references
homopropargylic alcohols also tolerated well in this reaction
and the desired products were isolated in 55% and 57% yields
(Scheme 2, 3r and 3s). The desired substituted nitrofurans with
electron-donating and electron-withdrawing substituents on
the benzene rings were also obtained in 46% and 45% yields
from this process, respectively (Scheme 2, 3u and 3v).
Unfortunately, the substrates with the -NH2, and –OH group
on the benzene ring did not fit this reaction system and no
desired products was detected.
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2 under the standard conditions
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intermediate A 14
.
The cation intermediate
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A
C
,
B
.
Finally,
C
catalyzed oxidative aromatization.
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