Tandem Oxidation Processes: The Direct Conversion of Activated Alcohols into Nitriles

Abstract

The direct conversion of primary alcohols into nitriles is reported (RCH₂OH into RCN) using manganese dioxide and ammonia in 2-propanol-THF, containing magnesium sulfate at room temperature. This transformation, which proceeds via an in situ oxidation-imination-aldimine oxidation sequence, has been applied to a range of benzylic, heterocyclic, allylic and propargylic alcohols.

oxidation - imines - nitriles - cyanides - one-pot

References

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1b Blackburn L. Wei X. Taylor RJK. Chem. Commun.  1999,  1337 

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2 Blackburn L. Pei C. Taylor RJK. Synlett  2002,  215 

3 Blackburn L. Taylor RJK. Org. Lett.  2001,  3:  1637 

4

For other tandem oxidation processes see the preceding and following papers in this series.

5a Lai G. Bhamare NK. Anderson WK. Synlett  2001,  230 

5b See also: Gilman NW. J. Chem. Soc., Chem. Commun.  1971,  733 

6

The products, which are all known, gave consistent spectroscopic data (and mps if solids).

7

Representative experimental: A 2 M solution of ammonia in 2-propanol (2.2 mL, 4.28 mmol; Aldrich) and anhydrous magnesium sulfate (1.93 g, 16.0 mmol) were added to a stirred solution of 4-bromobenzyl alcohol (0.200 g, 1.07 mmol) in THF (4.3 mL). Activated manganese dioxide (Aldrich 21764-6; 1.40 g, 16.10 mmol) was added to the solution. The resulting mixture was stirred at room temperature for 18 hours and then diluted with dichloro-methane (20 mL). The mixture was filtered through Celite^®, the Celite^® washed well with dichloromethane and the combined filtrates concentrated under reduced pressure. The solid residue was purified by column chromatography (silica gel, EtOAc-petroleum ether, 1:4) to give 4-bromobenzo-nitrile (157 mg, 81%) as a white solid, mp 112.8 °C, published mp (Aldrich) 112-114 °C.

8

Treatment of 2-cyanopyridine with ammonia in 2-propanol and THF containing magnesium sulfate and manganese dioxide at r.t. for 18 hours gave unreacted nitrile (30%) and carboxamide (50%). The fact that the nitrile appears to be formed first and is then converted into the carboxamide, appears to rule out a mechanism involving oxidation of an intermediate RCH(OH)NH₂ species.

9

Carboxamides were also observed with furan- and thio-phene-methanols.

10a For recent references see: Yang SH. Chang S. Org. Lett.  2001,  3:  4209 

10b Srinivas KVN. Reddy EB. Das B. Synlett  2002,  625 

10c Baxendale IR. Ley SV. Sneddon HF. Synlett  2002,  775