Srinivas
Ambala‡
ab,
Rohit
Singh‡
ab,
Maninder
Singh
a,
Pankaj Singh
Cham
a,
Ria
Gupta
ab,
Gurunadham
Munagala
ab,
Kushalava Reddy
Yempalla
ab,
Ram A.
Vishwakarma
ab and
Parvinder Pal
Singh
*ab
aMedicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, India. E-mail: ppsingh@iiim.ac.in
bAcademy of Scientific and Innovative Research, India
First published on 25th September 2019
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.
Considering the application of nitroolefins, development of an efficient, mild and practical method for the nitration of olefin 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 trifluoracetic acid (TFA) which offered high stereo-selectivity for styrenes and mono-substituted olefins (Fig. 1, left side, upper half).
Entry | Oxidant (equiv.) | Acid (equiv.) | Solvent | Time (h) | Yielda (%) |
---|---|---|---|---|---|
a Reaction conditions: styrene (1 mmol), aisolated yields, breaction carried at 70 °C, cwith one equivalent of NaNO2. | |||||
1 | K2S2O8 (2) | TFA (1) | DCM | 24 | 34 |
2 | K2S2O8 (2) | TFA (1) | DCM/H2O (2![]() ![]() |
24 | 67 |
3 | K2S2O8 (2) | TFA (1) | H2O | 4 | 32 |
4 | K2S2O8 (2) | TFA (1) | Acetone/H2O (2![]() ![]() |
4 | 38 |
5 | K2S2O8 (2) | TFA (1) | ACN/H2O (2![]() ![]() |
4 | 43 |
6 | K2S2O8 (2) | TFA (1) | DCE/H2O (2![]() ![]() |
4 | 68 |
7 | K2S2O8 (2) | — | DCM/H2O (2![]() ![]() |
24 | — |
8 | K2S2O8 (2) | TFA (1) | DCM/H2O (2![]() ![]() |
24 | 62 |
9 | K 2 S 2 O 8 (2) | TFA (1) |
DCM/H
2
O (2![]() ![]() |
4 | 71 |
10b | K2S2O8 (2) | TFA (1) | DCM/H2O (2![]() ![]() |
4 | 51 |
11 | K2S2O8 (2) | TFA (0.5) | DCM/H2O (2![]() ![]() |
4 | 48 |
12 | K2S2O8 (2) | TFA (1.2) | DCM/H2O (2![]() ![]() |
4 | 69 |
13c | K2S2O8 (2) | TFA (1) | DCM/H2O (2![]() ![]() |
4 | 44 |
14 | TBHP (2) | TFA (1) | DCM/H2O (2![]() ![]() |
4 | Trace |
To explore the scope of the reaction, as well as its suitability for the preparation of substituted nitroolefins, 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 corresponding E-β-nitro olefin in moderate to excellent yields (55–88%). The nature and position of the substituent had shown some influence 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 (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 α,α-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 condition to vinyl heterocycles, where 2-vinylfuran on attempt afforded the nitration product 4a in a yield of 63%. Moreover, aliphatic olefins 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, α,α-bisubstituted olefins gave a corresponding product 4d in a yield of 61% with E/Z ratio of 2:
1 (Schemes 1 and 2).
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 reported 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.
Footnotes |
† 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. |
This journal is © The Royal Society of Chemistry 2019 |