P. J. Amal Joseph et al. / Tetrahedron Letters 53 (2012) 1511–1513
1513
Table 2 (continued)
Acknowledgments
Entry
ArX
ArNO2
Yieldf (%)
P.J.A.J. thanks UGC New Delhi for the award of research fellow-
ship. S.P. thanks CSIR India for the award of fellowship.
Br
NO
2
22
62
78
N
N
I
NO2
Supplementary data
23
24
N
N
Supplementary data (general procedure for synthesis, charac-
terization data and copies of 1H and 13C NMR spectra of all the
compounds) associated with this article can be found, in the online
N
N
N
N
70
Br
O2N
a
Unless otherwise stated, reactions were performed on a 0.5 mmol scale with
haloarene (0.5 mmol), Cu(OSO2CF3)2 (25 mol %) and KNO2 (1.5 mmol) in dry DMSO
References and notes
(0.6 mL) at 130 °C for 48 h under N2 atmosphere.
b
Reactions performed at 120 °C.
Reaction performed at 125 °C.
Reactions performed with 30 mol % Cu(OSO2CF3)2 for 60 h.
Reaction performed at 135 °C.
1. (a) Parry, R.; Nishinob, S.; Spain, J. Nat. Prod. Rep. 2011, 28, 152; (b) Li, H.;
Huang, H.; Zhang, X.; Luo, X.; Lin, L.; Jiang, H.; Ding, J.; Chen, K.; Liu, H. Acta
Pharmacol. Sin 2008, 12, 1529; (c) Muller, W. E. The Benzodiazepine Receptor;
Cambridge University Press: New York, 1988; (d) Belciug, M.;
Ananthanarayanan, V. S. J. Med. Chem. 1994, 37, 4392; (e) Zollinger, H. Color
Chemistry; Wiley-VCH: New York, 1987. p 161; (f) Agrawal, J. P. Prop. Explos.
Pyrotech. 30 2005, 5, 316; (g) Fan, F.-R. F.; Yao, Y.; Cai, L.; Cheng, L.; Tour, J. M.;
Bard, A. J. J. Am. Chem. Soc. 2004, 126, 4035.
2. (a) Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH: New York, 2001;
(b) Vlasov, V. M. Russ. Chem. Rev. 2003, 8, 681; (c) Ballini, R.; Petrini, M.
Tetrahedron 2004, 60, 1017; (d) Tafesh, A. M.; Weiguny, J. Chem. Rev. 1996, 96,
2035.
3. (a) Shiri, M.; Zolfigol, M. A.; Kruger, H. G.; Tanbakouchian, Z. Tetrahedron 2010,
66, 9077; (b) Olah, G. A.; Malhotra, R.; Narang, S. C. Nitration: Methods and
Mechanisms; VCH: Weinheim, 1989.
4. Tani, K.; Lukin, K.; Eaton, P. E. J. Am. Chem. Soc. 1997, 119, 1476.
5. (a) Favresse, F.; Fargeas, V.; Charrue, P.; Lebret, B.; Piteau, M.; Quintard, J. J.
Organomet. Chem. 2000, 187; (b) Fargeas, V.; Favresse, F.; Mathieu, D.;
Beaudet, I.; Charrue, P.; Lebret, B.; Piteau, M.; Quintard, J. Eur. J. Org. Chem.
2003, 1711.
6. (a) Prakash, G. K. S.; Panja, C.; Mathew, T.; Surampudi, V.; Petasis, N. A.; Olah, G.
A. Org. Lett. 2004, 6, 2205; (b) Salzbrunn, S.; Simon, J.; Prakash, G. K. S.; Petasis,
N. A.; Olah, G. A. Synlett 2000, 1485; (c) Yang, H.; Li, Y.; Jiang, M.; Wang, J.; Fu,
H. Chem. Eur. J. 2011, 17, 5652; (d) Wu, X. F.; Schranck, J.; Neumann, H.; Beller,
M. Chem. Commun. 2011, 47, 12462.
7. For copper catalyzed ipso-nitration of iodoarenes and 4-bromoanisole; For
reference, see: Saito, S.; Koizumi, Y. Tetrahedron Lett. 2005, 46, 4715.
8. Very good yields were obtained by the application of microwave, albeit at
high catalyst and ligand loading; For reference, see: LaBeaume, P.; Placzek,
M.; Daniels, M.; Kendrick, I.; Ng, P.; McNeel, M.; Afroze, R.; Alexander, A.;
Thomas, R.; Kallmerten, A. E.; Jones, G. B. Tetrahedron Lett. 1906, 2010, 51.
9. (a) Fors, B. P.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 12898; (b) Prakash, G.
K. S.; Mathew, T. Angew. Chem., Int. Ed. 2010, 49, 1726.
c
d
e
f
Isolated yield.
afford the corresponding products in good yields (Table 2, entries
1–4, 10, 11, 15 & 16). On the other hand, the reaction of electron-
deficient haloarenes like 4-bromobenzophenone, 4-iodobenzonitri-
le, 4-bromobenzaldehyde, 3-bromobenzaldehyde, and 1-iodo-3-
nitrobenzene provided respective products in modest yields (Table
2, entries 5–9). The reactions of ortho-substituted haloarenes like
1-iodonaphthalene and 9-iodophenanthrene took prolonged time
to furnish the corresponding products in good yields (60 h, Table
2, entries 17 & 18). Similarly, the reaction of sterically hindered
2-iodo-1,3-dimethoxybenzene also afforded the product in moder-
ate yield, albeit at slightly higher temperature (135 °C, Table 2,
entry 19). It is important to note that several functional groups
including NO2, CHO, CN, COPh, NMe2, OCH2Ph, OMe, SMe, Ph, and
Me were tolerated in this method. However, the reaction failed to
yield the desired products for 4-bromoaniline and 4-iodophenol
substrates. Later, the scope of this method was effectively utilized
for the ipso-nitration of heterocycles like 2-bromopyridine,
3-bromoquinoline,
6-bromoquinoline,
1-(4-iodophenyl)-1H-
pyrrole, and 4-(4-bromophenyl)pyrimidine with good outputs
(Table 2, entries 20–24).
To demonstrate the application of this procedure in gram
scale, a reaction was performed using 10 mmol (2.030 g) of
4-bromothioanisole, 2.5 mmol of Cu(OSO2CF3)2 and 30 mmol of
KNO2 in 10 mL of dry DMSO at 130 °C for 48 h under nitrogen
atmosphere. The reaction proceeded smoothly to afford the corre-
sponding product 4-nitrothioanisole in a good yield (80%, 1.352 g)
and the unreacted starting material recovered was found to be 19%
(0.386 g).
In summary a very handy and efficient catalytic ipso-nitration
protocol that may find widespread applications in synthetic chem-
istry is presented. This procedure circumvents the use of expensive
ligands and phase transfer catalyst for the reaction. The protocol
merits complete regioselectivity, excellent functional group toler-
ance, and broad substrate scope. Several nitroarenes were synthe-
sized in moderate to good yields from various structurally
divergent haloarenes that includes iodoarenes, bromoarenes, and
heterocyclic haloarenes.
10. Bromoarenes are relatively cheaper than iodoarenes, and are practically
unexplored for ipso-nitration reaction; For reference, see:7–9.
11. This observation clearly confirms the absence of uncatalyzed SNAr mechanistic
pathway in this protocol.
12. A free radical mechanism is less likely in this protocol, because the reaction
proceeded in the presence of free radical inhibitor (3 equiv of TEMPO was used
as free radical inhibitor) for substrates such as 4-bromothioanisole and 1-iodo-
3-nitrobenzene under optimal conditions.
13. An oven dried pressure tube was charged with haloarenes (0.5 mmol),
copper(II) triflate (45 mg, 0.125 mmol), KNO2 (128 mg, 1.5 mmol) and
anhydrous DMSO (0.6 mL) under N2 atmosphere. The tube was sealed with a
Teflon screw cap having mininert valve and nitrogen is purged through it for
5 min. It is stirred at room temperature for 10 min and then the temperature
was gradually increased to 130 °C and is maintained at the same for 48 h. The
reaction mixture was then cooled to room temperature, washed with excess
ice cold water and extracted with ethyl acetate (3 Â 10 mL). The combined
organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated
under reduced pressure to give the crude product which was purified by
column chromatography using silica gel and a mixture of ethyl acetate and
hexane as the eluent to afford the desired products in good yields. For detailed
procedure; see Supplementary data.