9174
U. Azzena et al. / Tetrahedron 66 (2010) 9171e9174
A similar result, i.e., preferential or regioselective cleavage of an
Reaction products were characterized (1H NMR and IR) by
comparison with commercially available samples.
ortho CeBr bond vs a para CeCl bond, was obtained reacting 2-
bromo-4-chlorobenzoic acid, 6e, with 1.5 equiv of dianion 1c or 1a,
respectively (Scheme 5).17
Acknowledgements
Financial support from the Fondazione Banco di Sardegna
(Sassari, Italy) as part of the project ‘Reductive Dehalogenation of
Persistent Organic Pollutants’ is gratefully acknowledged.
2.4. Conclusion
The results reported above show that 1,2-diaryl-1,2-disodio-
ethanes behave as an activated form of Na metal, which find
useful application in the reductive cleavage of halogenated
benzoic acids, a reaction which cannot be promoted by the
metal alone.
Supplementary data
Supplementary data associated with this article can be found in
Accordingly, by taking into account the dependence of the
reducing power of these vic-diorganometals on their substitution
pattern (i.e., the less delocalized dianions are the more powerful
reducing agents, and vice versa) as well as the different order of
reducibility of the carbonehalogen bonds (either due to their rel-
ative bond strength and/or position with respect to the carboxylic
moiety), it was possible to obtain either the regioselective or the
exhaustive dehalogenation of a series of polyhalogenated benzoic
acids.
References and notes
1. Weber, R. Chemosphere 2007, 67, S109eS117 and references therein.
2. (a) For a review see: Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2002, 102,
4009e4091 for a selection of relevant literature, see: (b) Calo, V.; Nacci, A.;
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Monopoli, A.; Damascelli, A.; Ieva, E.; Cioffi, N. J. Organomet. Chem. 2007, 692,
4397e4401; (c) Huang, H.; Kobayashi, N.; Hasatani, M.; Matsuyama, K.; Sasaki,
T. Chem. Eng. Sci. 2007, 62, 5144e5149; (d) Moglie, Y.; Alonso, F.; Vitale, C.; Yus,
M.; Radivoy, G. Appl. Catal. A: Gen. 2006, 313, 94e100; (e) Matsunaga, A.; Ya-
suhara, A. Chemosphere 2005, 58, 897e904; (f) Alonso, F.; Moglie, Y.; Radivoy,
G.; Vitale, C.; Yus, M. Appl. Catal. A: Gen. 2006, 271, 171e176; (g) Miyoshi, K.;
Nishio, T.; Yasuhara, A.; Morita, M.; Shibamoto, T. Chemosphere 2004, 55,
1439e1446; (h) Miyoshi, K.; Kamegaya, Y.; Matsumura, M. Chemosphere 2004,
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2002, 43, 7247e7250; (j) Jackman, S. A.; Knowles, C. J.; Robinson, G. K. Che-
mosphere 1999, 38, 1889e1900.
3. Experimental section
3.1. General
3. Azzena, U.; Dettori, G.; Lubinu, C.; Mannu, A.; Pisano, L. Tetrahedron 2005, 61,
8663e8669.
Starting materials were of the highest commercial quality and
were purified by distillation or recrystallization immediately prior
to use. THF was distilled from Na/K alloy under N2 immediately
prior to use. All reactions were run under dry N2. 1H NMR spectra
were recorded at 300 MHz and 13C NMR spectra were recorded at
75 MHz in CDCl3 or DMSO-d6 with SiMe4 as an internal standard on
a Varian VXR 300 spectrometer. IR spectra were recorded on a FTIR
Jacso 680 P.
4. Azzena, U.; Pittalis, M.; Dettori, G.; Pisano, L.; Azara, E. J. Organomet. Chem. 2007,
692, 3892e3900.
5. Azzena, U.; Pisano, L.; Antonello, S.; Maran, F. J. Org. Chem. 2009, 74, 8064e
8070.
6. One referee suggested that these reducing agents could be better formulated as
dianions of the corresponding alkenes, with two electrons located in the LUMO
of the starting materials, acting as typical electron carriers. This is an in-
teresting observation, deserving a thorough analysis in the near future. Al-
though we agree that real structures are, most probably, highly delocalized
ones, we defined our reducing agents as 1,2-diaryl-1,2-disodioethanes, 1, both
because of their clean reactivity as dinucleophiles towards 1,3-dihalogeno-
propanes (see Ref. 3), as well as of the known reducing properties of other
benzylic polycarbanions; see, for example: Barry, C. E., III; Bates, R. B.; Beavers,
W. A.; Camou, F. A.; Gordon, B., III; Hsu, H. F.-J.; Mills, N. S.; Ogle, C. A.; Siahaan,
T. J.; Suvannachut, K.; Taylor, S. R.; White, J. J.; Yager, K. M. Synlett 1991, 207e212
and references cited therein.
7. Few alkali metal mediated reductions of halogenated benzoic acids were al-
ready reported. (a) For the reduction of fluorobenzoic acids with Na or K metal
in liquid NH3, see: Konovalov, V. V.; Laev, S. S.; Beregovaya, I. V.; Shchegoleva, L.
N.; Shteingarts, V. D.; Tsvetkov, Y. D.; Bilkis, I. J. Phys. Chem. A 2000, 104,
352e361 and references therein; (b) Few very old papers report on the re-
duction of halogenated benzoic acids with Na/Hg; see, for example: Geiner, P.;
Beilstein, F. Justus Liebigs Ann. Chem. 1866, 139, 1e16.
3.2. Starting materials
Benzoic acids 2aeg and 6aee are commercially available.
0.2e0.25 M solutions of dianions 1aed in dry THF were prepared as
already described.3e5
3.3. General procedure for the reductive dehalogenation of
benzoic acids 2aeh and 6aee
8. The reactivity of few mono- and di-halogenobenzenes towards 1,2-disodio-
1,2,3,4-tetraphenylethane, 1b, was already reported, see: Muller, E.; Roscheisen,
G. Chem. Ber. 1958, 91, 1106e1114.
€
€
A 0.20e0.25 M solution of a diorganometal 1 (1.8e4.8 mmol, see
Tables 1 and 2, and text) was added dropwise to a solution of the
appropriate halogenated benzoic acid (1.2 mmol) in dry THF
(10 mL), chilled at 0 ꢀC. The mixture was vigorously stirred and
allowed to reach rt during 12 h, after which time it was quenched
by slow dropwise addition of H2O (15 mL). The organic solvent was
evaporated in vacuo and the resulting mixture was extracted with
CH2Cl2 (3ꢄ10 mL). The organic phases were collected, extracted
with 1 N NaOH (3ꢄ10 mL), dried (Na2SO4) and, after evaporation of
the solvent, the residue was analyzed by 1H NMR. The aqueous
phases were collected, acidified with 1 N HCl and extracted with
CH2Cl2 (3ꢄ10 mL). The new organic phases were collected and
dried (Na2SO4). After evaporation of the solvent, the residue was
analyzed by 1H NMR.
9. (a) Li, X.;Zhang, Q.;Tang, L.; Lu, P.; Sun, F.; Li, L. J. Hazard. Mater. 2009,163,115e120;
ꢁ
ꢁ
ꢁ
ꢂ
ꢁ
ꢁ
ꢁ
(b) Novakova, H.; Vosahlõkova, M.; Pazlarova, J.; Mackova, M.; Burkhardb, J.;
ꢁ
Demnerova, K. Int. Biodeterior. Biodegrad. 2002, 50, 47e54; (c) Siciliano, S. D.;
Germida, J. J. Environ. Toxicol. Chem.1998, 17, 728e733; (d) Muccini, M.; Layton, A.
C.; Sayler, G. S.; Schultz, T. W. Bull. Environ. Contam. Toxicol. 1999, 62, 616e622.
10. Gassmann, J.; Voss, J. Z. Naturforsch. 2005, 60b, 1291e1299.
11. Gores, G. C.; Koeppe, C. E.; Bartak, D. E. J. Org. Chem. 1979, 44, 380e385.
12. Andrieux, C. P.; Saveant, J. M.; Zann, D. New J. Chem. 1984, 8, 107e116.
13. Attempted reduction of the preformed sodium salt of chloroacid 2d (by the
reaction of 2d with NaH in THF) with 1.0 equiv of 1b resulted in a very slow
reaction, affording a 33% conversion of the starting material after 24 h at rt. It is
worth noting the heterogeneity of such a reaction mixture.
14. Pierini, A. B.; Vera, D. M. A. J. Org. Chem. 2003, 68, 9191e9199 and references
therein.
15. For selected examples discussing the behaviour of aryl halides under electro-
chemical reduction conditions and leading to different apparent number of
electrons required in the cleavage step, see Ref. 12 and references therein.
16. In a separate experiment, reaction of benzoic acid, 2i, with 1b, in a 2:1 M ratio,
followed by D2O quenching and aqueous work up, led to the quantitative re-
covery of non deuterated 1,1,2,2-tetraphenylethane, 4.
Quenching with D2O was realized by adding 0.75 mL of the
electrophile to the reaction mixture, followed by aqueous work up
as described above.
17. Reduction of either 6d or 6e with dianion 1c in a 3:1 M ratio led to the recovery
of benzoic acid, 2i, in almost quantitative yield.