Convenient Reduction of Nitro Compounds to their Corresponding Amines with Promotion of NaBH₄/Ni(OAc)₂.4H₂O System in Wet CH₃CN

Introduction

Reduction of nitro compounds is one of the important methods for the preparation of aryl amines. Nitro compounds have traditionally been reduced by high-pressure hydrogenation¹. The application of NaBH₄ as a mild reducing agent has brought about fundamental changes in the reduction of functional groups in modern organic synthesis. It is known that solely sodium borohydride does not reduce nitro compounds under ordinary conditions ². However, the reducing power of this reagent or its polymeric analogue i.e., borohydride exchange resin (BER) undergoes a drastic change toward reduction of nitro groups by the combination with transition metal halides or salts such as NaBH₄/CoCl₂ ³,NaBH₄/FeCl₂ ⁴,NaBH₄/CuSO₄ ⁵, NaBH₄/Co(pyridyl) ⁶, NaBH₄/Cu(acac)₂ ⁷, borohydride exchange resin (BER); BER/ Ni(OAc)₂.4H₂O, CoCl₂, PdCl₂, Cu(OAc)₂ ⁸ are effective for the reduction of aliphatic or aromatic nitro compounds. It was reported that by the combination of transition metal halides or salts with NaBH₄ in protic or aqueous solvent systems ^{3, 8, 10} the formation of transition metal borides which are actively catalyzes-resulting from the decomposition of borohydride-with the evolving of hydrogen gas and in conjunction with the hydride attack reduce nitro compounds to their corresponding amines. Osby et al. ^9a reported that the combination of NaBH₄ with catalytic quantities of NiCl₂·6H₂O smoothly reduces aliphatic nitro compounds to their amines at room temperature. The method is successful for reduction of aliphatic nitro compounds. Also, Jia Wei Chen et al. ⁸ reported that the combination of NaBH₄ with BER/ Ni(OAc)₂.4H₂O smoothly reduces aromatic nitro compounds to their amines at room temperature. The method is successful for reduction of Aromatic nitro compounds. however Our preliminary experiments revealed that nitro compounds could reduce to corresponding amines by NaBH₄/NiCl₂.6H₂O/CH₃OH and  NaBH₄/Ni(OAc)₂.4H₂O/CH₃OH, but the amount of NaBH₄ and moderated yields of products (Table 1 & 2) in the best optimized reaction conditions (Table1 & 2, entry 4) are of disadvantages. On the other hand, the results of table (2) are better than table (1). We feel worthwhile to investigate one of the more highly reactive systems for reduction of nitro compounds to their corresponding amines, the literature survey could find no published example of nitro compounds reduction by this system (NaBH₄/Ni(OAc)₂·4H₂O/CH₃OH). To expand the above mentioned strategy in the reduction of nitro compounds by the NaBH₄/transation metal halide system and our continuous efforts to develop modified borohydride agents in organic synthesis ¹⁰, here we report that the combination of Ni(OAc)₂.4H₂O as a more efficient promoter for rapid and convenient reduction of nitro compounds with sodium borohydride in aqueous CH₃CN at room temperature.

Results And Discussion

Our preliminary experiments showed that the reduction of nitrobenzene with 4 molar equivalents of NaBH₄ and catalytic amounts of Ni(OAc)₂.4H₂O (0.2 mol) in CH₃CN (as an efficient aprotic solvent) without deposition of any precipitate was completed within 3 h under reflux conditions (Table 3, entry 4). However, a mixture of products with a 50 % yield of aniline was obtained from the reduction. In another attempt, it is found that by adding a small amount of water to the reaction mixture, when there was an immediate deposition of a fine black precipitate, the rate of reduction was dramatically increased and the reaction was completed within 20 min at room temperature (Table 3, entry 6). In the latter case, aniline was the sole product of reduction. The optimization reactions showed that using 4 molar equivalents of NaBH₄ and 0.2 molar equivalents of Ni(OAc)₂.4H₂O in a mixture of CH₃CN:H₂O (3.0:0.3 mL) are the best conditions for the complete conversion of nitrobenzene into aniline (scheme 1).

Scheme 1 Click here to View scheme

 

We applied the optimal conditions for the reduction of a variety of nitro compounds to their corresponding amines. As shown in Table 4. The product amines were obtained in high to excellent yields within 20–60 minutes. The chemoselective reduction of nitro group in the presence of carboxylic acid was proven with the reduction of 2-nitrobenzoic acid to anthranilic acid in 94% yield (table 4, entry 4). Our attempts to reduce C=O over nitro group in 2-nitrobenzaldehyde and 3′-nitroacetophenone were unsatisfactory and under the different conditions both of the functional groups were reduced (table 4, entries 5, 6). The complete reduction of nitroarenes with two nitro groups was also achieved perfectly by this protocol: using 8 molar equivalents of NaBH₄ in the presence of 0.2 molar equivalents of Ni(OAc)₂.4H₂O were the requirements for these transformations (table 4, entries 11, 12, 13). All attempts to perform chemoselective reduction of one nitro group in the presence of the other one were unsuccessful and the mixture of products was identified from the reaction mixture. Primary, secondary and tertiary aliphatic nitro compounds were rapidly reduced to their corresponding amines in excellent yields at room temperature (table 4, entries 15-17). The exact mechanism of this protocol is not clear; however, in our experiments, some results are noteworthy. In all reductions, by the combination of NaBH₄ with Ni(OAc)₂.4H₂O in wet CH₃CN, the immediate deposition of a fine black precipitate and the subsequent evolution of hydrogen gas were observed. We think that reduction of nitro compounds is probably due to formation of the black precipitate which catalyses the decomposition of NaBH₄, strongly adsorbs nitro compounds and activates them towards reduction by NaBH₄. This black precipitate may be boride, zerovalent metal or a mixture of these.

Conclusion

In conclusion we have shown that a variety of nitro compounds were reduced efficiently to their corresponding amines by the combination of NaBH₄ with catalytic amounts of Ni(OAc)₂.4H₂O in wet CH₃CN. The reductions were completed within 20–60 minutes at room temperature. We think that in the view points of molar equivalents of, NaBH₄ and catalyst, high efficiency, shorter reaction times, easy work-up procedure, and presentation of Ni(OAc)₂.4H₂O as a more efficient catalyst for the probable boride-catalysed reduction of aromatic and aliphatic nitro compounds, this protocol is a synthetically useful addition to the present methodologies.

Experimental Section

All reagents and substrates were purchased from commercial sources with the best quality and were used without further purification. IR and ¹H NMR spectra were recorded on   PerkinElmer FT-IR RXI and 300 MHz Bruker Avance spectrometers, respectively. The products were characterised by a comparison with authentic samples (melting or boiling points) and their ¹H NMR or IR spectra. All yields refer to isolated pure products. TLC was applied for the purity determination of substrates, products and reaction monitoring over silica gel 60 F254 aluminum sheet.

A Typical Procedure for Reduction of Nitrobenzene to Aniline with NaBH₄/NiCl₂.6H₂O Ssystem

In a round-bottomed flask (15 ml) equipped with a magnetic stirrer, a solution of nitrobenzene (0.123 g, 1 mmol) in CH₃CN-H₂O (3:0.3 ml) was prepared. To the resulting solution, NiCl₂.6H₂O (0.049 g, 0.2 mmol) was added and the mixture was then stirred for 5 min. Afterwards, NaBH₄ (0.151g, 4 mmol) as a fine powder was added to the reaction mixture and a fine black precipitate was immediately deposited. The mixture continued to be stirred for 20 min and the progress of the reaction was monitored by TLC (eluent; CCl₄/Et₂O: 5/2). At the end of reaction, distilled water (5 ml) was added to the reaction mixture and the mixture stirred for 10 min. The mixture was extracted with CH₂Cl₂ (3 × 8 ml) and dried over anhydrous sodium sulfate. Evaporation of the solvent and short column chromatography of the resulting crude material over silica gel (eluent; CCl₄/Et₂O: 5/3) gave the pure liquid aniline (0.085 g, 92%, entry 1, Table 4).

Table 1 Click here to View table

Table 2 Click here to View table

Table 3 Click here to View table

Table 4 Click here to View table

Acknowledgment

The authors gratefully appreciated the financial support of this, work by the research council of Islamic Azad University branch of Mahabad.

References

1. (a) Stiles, M.; Finkbeiner, H. L. J. Am. Chem. Soc, 81: 505 (1959). (b) Finkbeiner, H. L.; Stiles, M. J. Am. Chem. Soc, 85: 616 (1963).
2. (a) Burk, S. D. and Danheiser, R. L. Handbook of Reagents for Organic Synthesis, Oxidising and Reducing Agents, Wiley-VCH: New York, (1999). (b) Seyden-Penne, J. Reductions by the Alumino and Borohydrides in Organic Synthesis, Wiley-VCH: New York, (1997). (c) Hudlicky, M. Reductions in Organic Chemistry, Ellis Horwood, Chichester, (1984).
3. Satoh, T.; Suzuki, S.; Miyaji, Y.; Imai, Z. Tetrahedron Lett, 10: 4555 (1960).
4. Ono, A. H.; Sasaki, H.; Yaginuma, F. Chem. Ind. (London), 480 (1983).
5. Yoo, S. E.; Lee, S. H. Synlett, 419 (1990).
6. Hanaya, K.; Muramatsu, T.; Kudo, H.; Chow, Y. L. J. Chem. Soc. Perkin Trans. I,  2409 (1979).
7. (a) Chem, J. W.; Qin, C. Q. React. Polym, 16: 287(1992). (b) Yoon, N. M.; Choi, J. Synlett, 135 (1993).
8. Ganem, B.; Osbey, J. O. Chem. Rev, 86: 763(1986).
9. (a) Osby, J. O.; Ganem, B. Tetrahedron Lett, 26: 6413(1985). (b) Nose, A.; Kudo, T. Chem. Pharm. Bull, 29 (1981). (c) Sarma, J. C.; Borbaruah, M.; Sharma, R. P. Tetrahedron Lett. 26: 4657 (1985). (d) Sharma, D. N.; Sharma, R. D. Tetrahedron Lett, 26: 2581 (1985).
10. (a) Zeynizadeh, B.;  Setamdideh, D.  J. Chin. Chem. Soc, 52: 1179 (2005) (b) Setamdideh, D.; Zeynizadeh, B. Z. Naturforsch, 61b: 1275 (2006). (c) Zeynizadeh, B.; Setamdideh, D. Synth. Commun, 36: 2699 (2006). (d) Zeynizadeh, B.;  Setamdideh, D. and Faraji, F. Bull. Korean Chem. Soc, 29: 76 (2008).  (e) Zeynizadeh, B.;  Setamdideh, D. Asian J. Chem. 21: 3588 (2009). (f) Zeynizadeh, B.;  Setamdideh, D. Asian J. Chem, 21: 3603 (2009). (g) Setamdideh, D.; Khezri, B.  Asian J. Chem, 22: 5566 (2010).
11. Aldrich Catalogue of Fine Chemicals, (2004–2005).

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