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Selective Reduction of Nitro Compounds to Amines with Titanium(II) Reagents

James George and S. Chandrasekaran
Synthetic Communications 13(6), 495-499 (1983)

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The reduction of nitro compounds to amines, an important synthetic reaction, is usually accomplished by means of catalytic hydrogenation,1 metal and acids,2,3 reduction with hydride reagents4,5 and sulfurated sodium borohydride.6 A few attempts at the reduction of nitro groups using transition metal chlorides in the presence of sodium borohydride have also been reported. In general most of these methods have only limited applicability due to lack of selectivity subject to interference by other functional groups, low yields or unwanted side reactions.2,3 Quite a few of these reactions are performed under strongly acidic or basic, aqueous conditions and isolation of the amines from the reaction mixture poses a serious problem.

No.
Nitro compound Producta
Yieldb
1
NitrobenzeneAniline
92%
2
o-Nitrophenolo-Aminophenol
94%
3
p-Chloro-nitrobenzenep-Chloroaniline
92%
4
m-Dinitrobenzenem-Phenylenediamine
94%
5
Ethyl p-NitrobenzoateEthyl p-Aminobenzoate
98%
6
p-Nitro-benzonitrilep-Amino-benzonitrile
94%
7
NitrocyclohexaneCyclohexylamine
87%
8
2-Nitrobornane2-Aminobornane
89%
9
α-Nitronaphtalene α-Aminonaphtalene
95%
10
Allyl p-Nitrobenzoate Allyl p-Aminobenzoate
96%
  1. Products were characterised by comparison
    with authentic samples (spectra, TLC and mp).
  2. All yields refer to isolated products.

In our search for a mild, selective and general method for this transformation, we find that the Ti(II) species generated by the reduction of titanium tetrachloride with amalgamated magnesium offers a lot of advantages over the existing methods. Treatment of nitro compounds with amalgamated magnesium and titanium tetrachloride in THF/tert-butanol at 0C for 0.5-1.0 hr yields amines in excellent yields. A wide variety of aromatic and aliphatic nitro compounds have been reduced selectively in the presence of other interfering functional groups (Table). Particularly noteworthy are the entries 3, 6 and 10 in the Table, containing easily reducible functional groups like chloro, cyano and allylcarboxylate8 units respectively which are not affected under the reaction conditions.

From the data presented above it is evident that this methodology is mild, very selective and works efficiently under non-aqueous conditions.

Experimental

To a solution of mercuric chloride (0.091 g, 0.33 mmol) in 4 ml of dry THF was added 36 mesh magnesium (0.144 g, 6 mmol) and the mixture was stirred at room temperature under nitrogen for 10 min. The turbid supernatant liquid was withdrawn by syringe and the remaining amalgam was washed with three portions of THF. Dry THF (8 ml) was added and the mixture was cooled to -10C and treated with titanium tetrachloride (3 mmol) followed by the addition of the nitro compound (1 mmol) in THF (4 ml) and tertiary butanol (2 ml). Stirring was continued at 0C for 0.5-1.0 hr and then water (5 ml) was added followed by dilution with ether (50 ml) and filtered through a short pad of celite and silica-gel and washed with ether (30 ml). The amine was isolated after evaporation of the solvent.

References

  1. P. Rylander, "Catalytic Hydrogenation in Organic Synthesis," p. 114-134, Academic Press, New York, N.Y., 1979.
  2. C.A. Buehler and D.A. Pearson, Survey of Organic Synthesis, Vol. 1, p. 413-417. John Wiley and Sons, New York, N.Y., 1970.
  3. C.A. Buehler and D.A. Pearson, Survey of Organic Synthesis, Vol. 2, p. 395-397, John Wiley and Sons, New York, N.Y., 1977.
  4. J. Malek and M. Gerny, Synthesis, 217 (1972).
  5. R.O. Hutchins, D.W. Lamson, L. Rua, C. Milewski and Maryanoff, J. Org. Chem., 36, 803 (1971).
  6. J.M. Lalancette and J.R. Brindle, Can. J. Chem., 49, 2990 (1971).
  7. T. Satah, Y. Suzuki, S. Suzuki, Y. Suzuki, Y. Miyaji and Z. Imai, Tetrahedron Lett., 455 (1969).
  8. Allyl and benzyl esters are converted to the parent carboxylic acids on treatment with Ti(II)
    reagent after 4-8 hrs at 0C (J. George and S. Chandrasekaran, submitted for publication).