Metal-free, room temperature, acid-K2S2O8 mediated method for the nitration of olefins: An easy approach for the synthesis of nitroolefins

Article abstract of DOI:10.1039/c9ra06414a

Here, we have developed a simple, room temperature method for the nitration of olefins by using inexpensive sodium nitrite as a source of nitro groups in the presence of trifluoroacetic acid (TFA) and potassium persulfate (K₂S₂O₈) under an open atmosphere. Styrenes and mono-substituted olefins give stereo-selective corresponding E-nitroolefins under optimized conditions, however, 1,1-bisubstituted olefins give a mixture of E- and Z-nitroolefins. The optimized conditions work well with electron-donating, electron-withdrawing, un-substituted and heterocyclic styrenes and mono-substituted olefins and give corresponding nitroolefins with good to excellent yields.

Full text of DOI:10.1039/c9ra06414a

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Metal-free, room temperature, acid-K2S2O8
mediated method for the nitration of olefins: an
easy approach for the synthesis of nitroolefins†
Cite this: RSC Adv., 2019, 9, 30428
Srinivas Ambala,‡ab Rohit Singh,‡ab Maninder Singh,a Pankaj Singh Cham,a
Ria Gupta,ab Gurunadham Munagala,ab Kushalava Reddy Yempalla,ab
ab
Ram A. Vishwakarmaab and Parvinder Pal Singh
*
Here, we have developed a simple, room temperature method for the nitration of olefins by using
inexpensive sodium nitrite as a source of nitro groups in the presence of trifluoroacetic acid (TFA) and
potassium persulfate (K2S2O8) under an open atmosphere. Styrenes and mono-substituted olefins give
stereo-selective corresponding E-nitroolefins under optimized conditions, however, 1,1-bisubstituted
olefins give a mixture of E- and Z-nitroolefins. The optimized conditions work well with electron-
donating, electron-withdrawing, un-substituted and heterocyclic styrenes and mono-substituted olefins
and give corresponding nitroolefins with good to excellent yields.
Received 16th August 2019
Accepted 5th September 2019
DOI: 10.1039/c9ra06414a
rsc.li/rsc-advances
reaction always suffer with the formation of undesired E/Z
isomeric mixture of product.10a–d To address this, over the
Introduction
decade, many synthetic groups have also reported stereo-
selective nitration of olens. In this context, Maiti and co-
workers reported the stereo-selective nitration of aliphatic
and aromatic olens with in situ generated NO2 centred
radical from the nitrites (AgNO2, Fe(NO3)3 or t-BuONO) in the
presence of TEMPO (Fig. 1, right side, upper half).11–14 In the
similar pattern, Guo et al. also developed another method
using combination of sodium nitrite (NaNO2), potassium
persulfate and TEMPO (Fig. 1, right side, upper half).14 In
another attempt, Kuhakarn et al. reported the stereo-selective
nitration of olen using radical based species generating
from the reaction of sodium nitrite (NaNO2), oxone and
potassium iodide (Fig. 1, lower half).15 All these stereo-
selective methods are productive, but either employed high
temperature or stoichiometric amounts of reagents such as
TEMPO.
Considering the application of nitroolens, development
of an efficient, mild and practical method for the nitration of
olen is highly desirable. The present concept is developed
considering the stability of nitrite where it is well known that
nitrous acid is highly reactive in comparison to their metal
salt which may initiate the reaction at room temperature.
Upon several attempts, a mild and room temperature method
was developed for the nitration of alkenes in the combination
of sodium nitrite (NaNO2) and potassium persulfate (K2S2O8)
and triuoracetic acid (TFA) which offered high stereo-
selectivity for styrenes and mono-substituted olens (Fig. 1,
le side, upper half).
Nitroolens are intriguing synthetic units and have been
used for the generation of biological, pharmaceutical,
materials, and agrochemical relevant molecules.1a–e More-
over, these are used as starting materials for various C–C
bond forming reactions2–4 and have been utilized in the
synthesis of diverse chemically interesting molecules, viz.,
oximes, hydroxylamines, nitroalkanes, aliphatic amines, and
nitroso compounds.5a,b Accordingly, considerable efforts
have been made in the synthesis of nitroolens including the
Henry reaction, which involves the base mediated conden-
sation of an aldehyde or ketone with a nitroalkane.6 The
other approach used for the synthesis of nitroolens involved
the nitration of olens using a mixture of HNO3 and conc.
sulfuric acids, where the reaction efficiency is signicantly
hampered by the production of a large amount of acid waste
as well as nitrogen oxide fumes.7 Alternatively, nitro alkenes
are also synthesized by the decarboxylative nitration of a,b-
unsaturated carboxylic acids.8a,b,9 However, the direct incor-
poration of a nitro group on an olen is considered as the
preferred approach. In this direction, several synthetic
methods have been reported employing transition metals
and gaseous nitrating agents. These methods offer signi-
cant improvements over the previous methods but the
aMedicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, India.
E-mail: ppsingh@iiim.ac.in
bAcademy of Scientic and Innovative Research, India
† Electronic supplementary information (ESI) available: Copies of 1H NMR, 13C
NMR and mass spectra of synthesized compounds. See DOI: 10.1039/c9ra06414a
‡ S. A. and R. S. contributed equally to this work.
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afforded product 2a in a yield of 32% (entry 3). In another
attempts with other solvent systems such as acetone : water,
acetonitrile (ACN) : water, 1,2-dichloroethane (DCE) : water, the
reaction underwent but with comparatively lower yield except
DCE : water which gave almost similar results as obtained with
DCM : water (entries 4–6). Surprisingly, no reaction was
observed in the absence of TFA (entry 7). With increase amount
of K2S2O8, the formation of 2a was observed in a yield of 62%,
the increased amount might cause degradation of the product
(entry 8). Lower yield of the 2a was observed at higher temper-
ature 70 ꢀC (entry 10). Next, the effect of TFA concentrations was
also studied (entries 11 & 12), where both increase and decrease
in its concentration affect the yield and best result was obtained
with one equivalent of TFA. When the concentration of NaNO2
was decreased, the formation of 2a also gets affected drastically.
When the oxidant K2S2O8 was replaced with other organic
oxidant such as tert-butylhydroperoxide (TBHP), only traces
amount of required product was observed (entry 14).
To explore the scope of the reaction, as well as its suitability
for the preparation of substituted nitroolens, a variety of
styrenes having electron-withdrawing as well as electron-
donating groups were tried under optimized condition. As
shown in Schemes 1 and 2, reaction conditions were compatible
to all the substituted styrenes, and transformed into the corre-
sponding E-b-nitro olen in moderate to excellent yields (55–
88%). The nature and position of the substituent had shown
some inuence on the reaction. The mono-substituted styrenes
having electron-donating groups like –Me, –OMe and t-butyl at
C4 position gave the desired nitro product in better yields
compared with C2 position (2b-75%, 2c-70%, 2d-81%, 2e-72%,
and 2f-88%). Furthermore, substrates such as di- and tri-
substituted styrenes were also found to be the suitable
substrates and afford the corresponding products in good yields
Fig. 1 Literature precedent and present method for nitration of
olefins.
Results and discussion
Initially, we started the study with styrene 1a in the presence of
NaNO2 and K2S2O8 as a model substrate for the nitration.
Screening of the reaction conditions are shown in Table 1. First
reaction was performed by reacting 1a (1.0 mmol) with NaNO2,
K2S2O8 and TFA in DCM under open atmosphere, the formation
of required product, (E)-(2-nitrovinyl)benzene 2a was observed
with the yield of 34% (entry 1). In a next attempt, we conducted
the reaction in a mixture of DCM : water, signicant improve-
ment in the yield of 2a from 34 to 71% was observed (entry 2).
However, the reaction in water alone didn't seem good which
Table 1 Optimization studiesa
Entry
Oxidant (equiv.)
Acid (equiv.)
Solvent
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
TBHP (2)
TFA (1)
TFA (1)
TFA (1)
TFA (1)
TFA (1)
TFA (1)
—
TFA (1)
TFA (1)
TFA (1)
TFA (0.5)
TFA (1.2)
TFA (1)
TFA (1)
DCM
DCM/H2O (2 : 1)
H2O
24
24
4
4
4
34
67
32
38
43
68
—
62
71
51
48
69
44
Trace
Acetone/H2O (2 : 1)
ACN/H2O (2 : 1)
DCE/H2O (2 : 1)
DCM/H2O (2 : 1)
DCM/H2O (2 : 1)
DCM/H2O (2 : 1)
DCM/H2O (2 : 1)
DCM/H2O (2 : 1)
DCM/H2O (2 : 1)
DCM/H2O (2 : 1)
DCM/H2O (2 : 1)
4
24
24
4
4
4
4
4
4
9
10b
11
12
13c
14
a
Reaction conditions: styrene (1 mmol), aisolated yields, breaction carried at 70 ꢀC, cwith one equivalent of NaNO2.
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Scheme 3 Nitration in different condition.
When the reaction of styrene 1, was performed under the
optimized conditions in the presence of free-radical scavenger,
TEMPO, nitro-substituted styrene 2a was obtained in a yield of
70% (eqn (1), Scheme 3), no suppression was observed. It might
be due to the TEMPO-adduct undergo elimination and
produced nitro-containing product in a similar fashion re-
ported by Maity et al.13 In the next experiment, when the proton
source was changed and used acetic acid and HCl, the reactions
underwent and the gave the product 2a in a yield of 58% and
55%, respectively (eqn (2) and (3), Scheme 3). In the next part,
NO2 source was also changed and used tert-butyl nitrite in place
of sodium nitrite which gave the required product in a yield of
41%. These results further expands the utility of method.
Scheme 1 Nitration of styrenes.
(2g-55%, 2i-74%, 2j-75%, 2k-75%, and 2l-81%). It is important
to note that diminished yields were observed with various
styrene derivatives having electron-withdrawing groups (–F, –Cl,
–Br, –CF3, –CN) 2m-75%, 2n-68%, 2o-71%, 2p-69%, 2q-62%, 2r-
59%, 2s-55%, and 2t-65%). Furthermore, styrene substituted
with labile functional groups like ester also underwent smooth
coupling and converted to the corresponding nitrostyrene 2u
with 78% yield. Next, under the optimized conditions, we
investigated the nitration of vinylnapthalene and biphenyl
styrene, which affords the nitration product 2v and 2w in a yield
of 55% and 70%, respectively. Moreover, the reaction with a,a-
bisubstituted styrenes gave E : Z mixture of the corresponding
nitrated products 2x and 2y in 68% and 66% yield, respectively.
In addition, we also expanding the present reaction condi-
tion to vinyl heterocycles, where 2-vinylfuran on attempt affor-
ded the nitration product 4a in a yield of 63%. Moreover,
aliphatic olens such as nonene and hexene when tried, reacted
smoothly and gave corresponding products 4b and 4c in a yield
of 63% and 71%, respectively. However, a,a-bisubstituted
olens gave a corresponding product 4d in a yield of 61% with
E/Z ratio of 2 : 1 (Schemes 1 and 2).
Conclusion
In summary, we have developed a simple, room temperature
method for the nitration of olens with sodium nitrite, TFA and
potassium persulphate under open atmosphere. This method
give high stereo-selective E-nitroolens with styrenes and
mono-substituted olens. The use of diverse range of acids and
nitro-sources provide additional advantage. The study with
other substrates and application is under progress and will be
published in due course.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
This work was supported by Council of Scientic and Industrial
Research (CSIR)-New Delhi with research grant #BSC0108 and
#HCP0008. SA, RS, MS, GM and KRV thanks UGC and CSIR for
their Fellowship. RG thanks DST for fellowship. Institutional
manuscript number "IIIM Comm. No. CSIR-IIIM/IPR/0095".
Scheme 2 Nitration of vinyl heteroarenes and aliphatic olefins.
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