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N-Methylmorpholine-N-Oxide (NMO)

N-Methylmorpholine-N-Oxide (NMO) is available commercially as the monohydrate; it has a melting point of 70 C, and is stable under normal conditions. This reagent is soluble in polar solvents, especially water.

NMO displays characteristic reactivity with various transition metals, which undergo oxidation with this reagent. Because of this, NMO is a preferred stoichiometric oxidant for transition metal-catalyzed oxidations.

The well-known combination of NMO and TPAP (tetrapropylammonium perruthenate) can, for example, be used in the preparation of aldehydes from primary alcohols, wherein the water produced must be taken up by molecular sieves. The presence of water fosters an equilibrium concentration of the aldehyde hydrate, which can undergo further oxidation to the carboxylic acid. (Review: S. Ley, J. Norman, W. P. Griffith, S. P. Marsden, Synthesis, 1994, 639. Abstract)

Name Reactions

Upjohn Dihydroxylation

Recent Literature

Tetrapropylammonium perruthenate enables oxidations of a wide range of molecules including examples of both double oxidations and selective oxidations. Mechanistic studies and general experimental procedures are reported. In addition several interesting developments in the chemistry of this reagent are outlined: heteroatom oxidation, cleavage reactions and use in sequential reaction processes.
S. B. Ley, J. Norman, W. P. Griffith, S. P. Marsden, Synthesis, 1994, 639-666.

he mild instability of the Ley-Griffith catalyst (TPAP) creates preparation, storage, and reaction reproducibility issues, due to unpreventable slow decomposition. A set of readily synthesized, bench stable, phosphonium perruthenates (ATP3 and MTP3) mirror the reactivity of TPAP, but avoid storage decomposition issues.
P. W. Moore, C. D. G. Read, P. V. Bernhardt, C. M. Williams, Chem. Eur. J., 2018, 24, 4556-4561.

An efficient method for the oxidation of an olefin to the less substituted carbonyl compound is described. This one pot conversion includes hydroboration with borane dimethyl sulfide (BDMS), followed by oxidation of the resulting alkylboranes with tetrapropylammonium perruthenate (TPAP) and NMO.
M. H. Yates, Tetrahedron Lett., 1997, 38, 2813-2816.

The use of PhI(OAc)2 in dichloromethane enables a clean oxidative cleavage of 1,2-diols to aldehydes. In the presence of OsO4 as catalyst, NMO and 2,6-lutidine, olefinic bonds can be cleaved in acetone/water to yield the corresponding carbonyl compounds.
K. C. Nicolaou, V. A. Adsool, C. R. H. Hale, Org. Lett., 2010, 12, 1552-1555.

In a simple, mild, and highly effective method for the direct conversion of primary alcohols to carboxylic acids, TPAP serves as the catalyst, and NMO • H2O plays a dual role, acting as the co-oxidant and as a reagent for aldehyde hydrate stabilization. This previously unknown stabilizing effect of geminal diols by N-oxides is the key for the efficiency of the overall transformation.
A.-K. C. Schmidt, C. B. W. Stark, Org. Lett., 2011, 13, 4164-4167.

The ionic liquids [C4mim][PF6] and [C8mim][PF6] as cosolvents in asymmetric dihydroxylation give yields and enantioselectivity comparable or higher than those of the conventional H2O/tert-BuOH solvent system. After extraction of the reaction mixture with diethyl ether, the contamination of the product by osmium was remarkably low. The reuse of ionic liquid and catalyst is possible.
L. C. Branco, C. A. M. Afonso, J. Org. Chem., 2004, 69, 4381-4389.

Resin-OsO4 are very efficient catalysts for the dihydroxylation of various olefins to afford vicinal diols with high yields irrespective of the cooxidant used. Resin-OsO4 is recovered quantitatively by a simple filtration and reused for a number of cycles with consistent activity. The high binding ability of the heterogeneous osmium catalysts enables the use of an equimolar ratio of a chiral ligand such as (DHQD)2PHAL to osmium to give excellent enantioselectives in the asymmetric dihydroxylation.
B. M. Choudary, N. S. Chodari, K. Jyothi, M. L. Kantam, J. Am. Chem. Soc., 2002, 124, 5341-5349.

Osmium tetroxide has been microencapsulated in a polyurea matrix. These microcapsules have been effectively used as recyclable catalysts in the dihydroxylation and the oxidative cleavage of olefins.
S. V. Ley, C. Ramarao, A.-L. Lee, N. Ostergaard, S. C. Smith, I. M. Shirley, Org. Lett., 2003, 5, 185-187.

cis-Dihydroxylation of olefins with a catalytic amount of osmium tetroxide and N-methylmorpholine N-oxide proceeds smoothly in an organic solvent in the presence of dihydroxyphenylborane to give the corresponding phenylboronic esters in good yields. The use of a diol captor prevents further oxidation of the products and makes the isolation procedure easier.
I. Nobuharu, K. Takashi, N. Koichi, Chem. Lett., 1988, 1721-1724.

The use of N-oxides in butanol as solvent enables a site-selective oxidation of vicinal bis(boronates) with good efficiency and selectivity across a range of substrates to provide 2-hydro-1-boronic esters, which are shown to be versatile intermediates in the synthesis of chiral building blocks.
L. Yan, J. P. Morken, Org. Lett., 2019, 21, 3760-3763.

The cis-dihydroxylation of olefin-containing potassium alkyl- and aryltrifluoroborates proceeds readily in moderate to excellent yields. The resulting diols are efficient coupling partners in Suzuki-Miyaura-type reactions with both alkenyl and aryl bromides.
G. A. Molander, R. Figueroa, Org. Lett., 2006, 8, 75-78.

A new one-pot method is described for the removal of O- and N-allyl protecting groups under oxidative conditions at near neutral pH. The allyl group undergoes hydroxylation and subsequent periodate scission of the vicinal diol. Repetition of this reaction sequence on the enole tautomer of the aldehyde intermediate releases the deprotected functional group.
P. I. Kitov, D. R. Bundle, Org. Lett., 2004, 3, 2835-2838.