Hari K.
Kadam
and
Santosh G.
Tilve
*
Department of Chemistry, Goa University, Taleigao Plateau, Goa–403206, India. E-mail: stilve@unigoa.ac.in; Fax: +91-832-2452886; Tel: +91-832-6519317
First published on 25th April 2012
Copper(II) bromide as a procatalyst for the in situ preparation of active Cu nanoparticles for the efficient reduction of nitroarenes using sodium borohydride is described. During reduction, Cl, I, COOH, aliphatic nitro and OCH2Ph groups remain intact displaying the chemoselectivity of the process. The method is also useful for the reduction of cyano and olefinic compounds. Scalability of the method was demonstrated up to 100 mmol.
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Scheme 1 Reduction of nitroarenes. |
Entry | Catalyst | % Anilineb | % Nitrobenzeneb |
---|---|---|---|
a Reaction conditions: nitrobenzene (1 mmol), catalyst (10 mol%), ethanol (5 mL), NaBH4 (3–5 mmol), r.t., 5 h. b Isolated yield. c Cu nano (1 mmol), 24 h. d CuO (> 1 mmol), NaBH4 (5 mmol), 35 h. e Cu2O (1 mmol), NaBH4 (5 mmol), 24 h, deposited Cu metal seen on the surface of reaction vessel. | |||
1 | Cu nanoc | 34 | 40 |
2 | Cu-acetate | 12 | 46 |
3 | CuCl2 | 22 | 60 |
4 | CuBr2 | 90 | 0 |
5 | CuI | 41 | 20 |
6 | CuOd | 0 | 100 |
7 | Cu2Oe | 68 | 18 |
8 | FeCl3 | 5 | 70 |
Amongst the catalysts tried, CuBr2 was found to be the catalyst of choice for giving a high yield of aniline within a short period of time (5 h). The formation of Cu nanoparticles in the range 30–40 nm was confirmed by TEM (Fig. 1) images of the recovered catalyst (see ESI†). XRD and EDX studies of the recovered catalyst show the presence of Cu2O along with Cu possibly due to atmospheric oxidation of the catalyst. Also, in the SEM images, micron-sized cubes of Cu2O are observed. To further confirm if there is any role of the oxides during the reduction, the reaction was attempted using CuO and Cu2O. In the case of CuO there was no reduction observed (Entry 6, Table 1) whereas Cu2O (Entry 7, Table 1) showed that reduction does take place, but this may be due to the active copper metal formed which was deposited on the surface of the reaction flask. Other Cu halides and Cu(II) acetate catalyst were also found to catalyze the reaction but to a lesser extent.
Next, various polar protic solvents like water, ethanol, etc. and aprotic solvents like THF were examined (Table 2).
Entry | Solvent | % Anilineb | % Nitrobenzeneb |
---|---|---|---|
a Reaction conditions: nitrobenzene (1 mmol), CuBr2 (10 mol%), solvent (5 mL), NaBH4 (3–5 mmol), r.t., 5 h. b Isolated yield. c 35 h. d NaBH4 (5 mmol). | |||
1 | Water | 50 | 15 |
2 | Ethanol | 90 | 0 |
3 | THF | 30 | 45 |
4 | Isopropanolc | 41 | 50 |
5 | n-Butanolc | 10 | 72 |
6 | t-Butanolc | 15 | 64 |
7 | Methanold | 91 | 0 |
The study showed ethanol and methanol to be the best solvents for this catalytic system. Methanol was avoided for further applications due to its harmful effects. Reduction was very slow in other branched and long chain alcohols.
The mole percent of CuBr2 and reaction temperature were then optimized by varying the catalyst amount and temperature (Table 3) and found that 10 mol% of CuBr2 gave the maximum yield (∼90%) at room temperature and increasing the catalyst amount or the temperature did not improve the yield of reduced product. It was expected that the reduction would take place more rapidly at higher temperature. It appears that the rapid decomposition of sodium borohydride at higher temperature might be responsible for the observed results.
Entry | Mole (%) | % Anilineb | % Nitrobenzeneb |
---|---|---|---|
a Reaction conditions: nitrobenzene (1 mmol), CuBr2 (5, 10, 20 mol%), ethanol (5 mL), NaBH4 (3 mmol), r.t. or 60 °C, 5 h. b Isolated yield. | |||
1 | 5 | 35 | 52 |
2 | 10 | 90 | 0 |
3 | 20 | 90 | 0 |
4 | 10 (60 °C) | 21 | 36 |
A scalability study with nitrobenzene revealed that reproducible isolated yields were obtained at both 0.1 mmol and 100 mmol scale (90 and 92% respectively.)
The recovered catalyst was again used for 3 consecutive cycles of reduction with nitrobenzene and yields were found to be consistent up to 3 catalytic cycles with increasing duration of reaction, this was expected as Cu nanoparticles tend to oxidise on exposure to air and moisture.
To study the generality and selectivity of this system, various nitroarenes were subjected to reduction (Table 4).
Entry | Reactant | Product | Time (h) | % Yieldb |
---|---|---|---|---|
a Reaction conditions: nitroarenes (1 mmol), CuBr2 (10 mol%), ethanol (5 mL), NaBH4 (3–5 mmol), r.t., 5–12 h. b Isolated yield. c See ref. 8 for spectral data comparison. d See ref. 24. for spectral data comparison. n.r.: no reaction, reactant recovered. | ||||
1 |
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5 | 90 |
2 |
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5 | 93 |
3 |
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5 | 90 |
4 |
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3 | 85 |
5 |
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8 | 78 |
6 |
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4 | 82 |
7 |
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3.5 | 88 |
8 |
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12 | 85 |
9 |
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14 | 84 |
10 |
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10 | 86 |
11 |
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5 | 92 |
12 |
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12 | 89c |
13 |
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12 | 82c |
14 |
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10 | 88 |
15 |
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9 | 87 |
16 |
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9 | 91d |
17 |
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— | 12 | n.r. |
18 |
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— | 12 | n.r. |
19 |
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0.5 | 96 |
20 |
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1 | 95 |
Along with nitrobenzene (Entry 1), p-,o-,m-nitrotoluenes (Entry 2, 3, 11) were readily reduced to p-,o-,m-toluidines. As expected o-nitrobenzaldehyde (Entry 4) rapidly gave o-aminobenzyl alcohol as the sole product. The acid group (Entry 5, 10) was intact and gave the respective aminobenzoic acids after long reaction times. Halogens like chloro and iodo (Entry 6, 18) were retained in the products displaying a selectivity that is usually not obtained when noble metals are used. Functionalities like hydroxyl and amino groups (Entry 7, 9) were not affected in this catalytic system. m-Dinitrobenzene (Entry 8) was completely reduced to m-aminoaniline with 5 eq. of sodium borohydride and no m-nitroaniline was observed during the course of reaction (tlc). This system very well retained the O-benzyl protection during nitro reduction (Entry 13) unlike catalytic hydrogenation, but the allylic double bond (Entry 12) was found to reduce completely. m-Nitroethylcinnamate was reduced to m-aminodihydroethylcinnamate (Entry 15) indicating that conjugated double bonds are also reduced in this system. This was further confirmed by reduction of ethylcinnamate to dihydroethylcinnamate (Entry 16) more efficiently than in an earlier report22 which used an excess of copper salt. Functional group CN (Entry 14) was completely reduced to benzyl amine. Aliphatic nitro group (Entry 17) was unaffected by this catalytic system. Ethyl 3-(3’-aminophenyl)propanoate (Entry 15) obtained in 87% yield using this method forms the building block of 1-pyrazolyl-3-phenylurea-p38-MAP kinase inhibitors (Fig. 2) which are used for the treatment of inflammation and hyperproliferative diseases.23
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Fig. 2 1-Pyrazolyl-3-phenylurea-p38-MAP kinase inhibitor. |
To understand the mechanism of the reduction process in this method, some of the known intermediates like nitrosobenzene and azobenzene (Table 4, Entry 19, 20) were subjected to this reduction protocol and were found to reduce completely to aniline as the only product within 0.5 and 1 h respectively. The mechanism (Fig. 3) for the reduction of nitroarenes probably follows both reduction pathways via directly from hydroxyl amine and via azobenzene intermediates. The reduction probably takes place on the active surface of Cu nanoparticles by the liberated hydrogen formed by decomposition of sodium borohydride. The proposed mechanism is further supported by reduction of nitrobenzene using hydrogen gas (60 psi at room temperature) and employing excess active copper (> 1 equiv.) prepared separately from CuBr2 and sodium borohydride.
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Fig. 3 Proposed mechanism. |
Footnote |
† Electronic Supplementary Information (ESI) available: spectral data of selected reduction products are available along with XRD, SEM, EDX & TEM images of recovered copper catalyst after nitro reduction. See DOI: 10.1039/c2ra20371e |
This journal is © The Royal Society of Chemistry 2012 |