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

<A NAME="RD08802ST-1A">1a</A> Wei X. Taylor RJK. Tetrahedron Lett.  1998,  39:  3815 

<A NAME="RD08802ST-1B">1b</A> Blackburn L. Wei X. Taylor RJK. Chem. Commun.  1999,  1337 

<A NAME="RD08802ST-1C">1c</A> Wei X. Taylor RJK. J. Org. Chem.  2000,  65:  616 

<A NAME="RD08802ST-1D">1d</A> Runcie KA. Taylor RJK. Chem. Commun.  2002,  974 

<A NAME="RD08802ST-2">2</A> Blackburn L. Pei C. Taylor RJK. Synlett  2002,  215 

<A NAME="RD08802ST-3">3</A> Blackburn L. Taylor RJK. Org. Lett.  2001,  3:  1637 

<A NAME="RD08802ST-4">4</A>

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

<A NAME="RD08802ST-5A">5a</A> Lai G. Bhamare NK. Anderson WK. Synlett  2001,  230 

<A NAME="RD08802ST-5B">5b</A> See also: Gilman NW. J. Chem. Soc., Chem. Commun.  1971,  733 

<A NAME="RD08802ST-6">6</A>

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

<A NAME="RD08802ST-7">7</A>

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.

<A NAME="RD08802ST-8">8</A>

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.

<A NAME="RD08802ST-9">9</A>

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

<A NAME="RD08802ST-10A">10a</A> For recent references see: Yang SH. Chang S. Org. Lett.  2001,  3:  4209 

<A NAME="RD08802ST-10B">10b</A> Srinivas KVN. Reddy EB. Das B. Synlett  2002,  625 

<A NAME="RD08802ST-10C">10c</A> Baxendale IR. Ley SV. Sneddon HF. Synlett  2002,  775