Organic Reagents

By James Ashenhurst

Reagent Friday: OsO4 (Osmium Tetroxide)

Last updated: January 29th, 2020 |

OsO4 (Osmium Tetroxide) As A Reagent For the Dihydroxylation Of Alkenes

In a blatant plug for the Reagent Guide, each Friday  I profile a different reagent that is commonly encountered in Org 1/ Org 2. 

Today’s reagent is among one of the best and most useful at what it does in all of organic chemistry. It’s blindingly good, in fact. So blinding, I don’t know if I’ve ever seen an example of it being used in an undergraduate teaching lab. It’s not a reagent for rookies: it’s genuinely dangerous, and should be handled with extreme care.

OsO4 For The Formation Of Vicinal Diols From Alkenes

Osmium tetroxide (OsO4) is a volatile liquid that is most useful for the synthesis of 1,2 diols  from alkenes. (Side note: another name for 1,2 diols is vicinal diols, or vic-diols). The reaction is very mild, and usefully leads to the formation of syn diols. Another side note: this reaction doesn’t work with alkynes.


Alkene Dihydroxylation With Osmium Tetroxide (OsO4): How It Works

The reaction works through a concerted process whereby two oxygens from the osmium interact with one face of the double bond. This results in a 5-membered ring (called an osmate ester) and generates the syn stereochemistry. The osmate ester is broken up into the 1,2-diol by use of an aqueous solution of a reducing agent such as potassium bisulfite, KHSO3. This is frequently omitted in textbooks (the mechanism is tedious to write out), but is worth mentioning just in case.


By the way, dihydroxylation of alkenes can also be performed with cold, dilute potassium permanganate (KMnO4). One advantage of OsO4 is that it is much more compatible with other functional groups than KMnO4, which is kind of a ravenous beast.

Why is osmium “blindingly good”? One of the molecules required for vision is retinol:


What do you think would happen if the vapors from OsO4 reached your eyes? Everything would go dark, let me tell you.

The good news is that apparently the blindness wears off after several months.

P.S. You can read about the chemistry of OsO4 and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF.

P.P.S. One preparation in Woodward’s synthesis of cortisone (subscription req’d) calls for  Osmium tetroxide (68.48 g) . Talk about courage!!!


(Advanced) References and Further Reading

  1. Oxydation ungesättigter Verbindungen mittels organischer Superoxyde
    Nikolaus Prileschajew. Chemische Berichte, 1909, 42, 4811. DOI: 10.1002/cber.190904204100
    This reaction (epoxidations of alkenes with a peracid) is also known as the Prizelhaev reaction after the author.
  2. The oxidation of olefins with perbenzoic acids. A kinetic study
    M. Lynch and  K. H. Pausacker. J. Chem. Soc. 1955, 1525-1531. DOI: 10.1039/JR9550001525
    One of the earliest papers on epoxidation with m-CPBA, comparing its reactivity with other substituted peracids. As expected, the reactivity of peroxyacids is increased by electron-withdrawing groups.
    Richard N. McDonald, Richard N. Steppel, and James E. Dorsey. Synth. 197050, 15. DOI: 10.15227/orgsyn.050.0015
    A reliable preparation for m-CPBA (which is commercially available) in Organic Syntheses. As this procedure shows, m-CPBA is not prepared as a pure compound (it is a mixture of the peracid and acid, and commercial samples may contain residual water for stability).
  4. Epoxidations with m-Chloroperbenzoic Acid
    Nelson N. Schwartz and John H. Blumbergs. J. Org. Chem. 1964 29, (7), 1976-1979. DOI: 1021/jo01030a078
    This paper describes mechanistic studies of m-CPBA oxidation that demonstrate that ionic intermediates are not involved in the reaction, and that the rate is insensitive to solvent polarity.
  5. Record of chemical progress
    Bartlett, P. D. Chem. Prog. 1950, 11, 47
    This is the publication in which Prof. P. D. Bartlett describes the ‘butterfly mechanism’ for m-CPBA epoxidation.
  6. MCPBA Epoxidation of Alkenes: Reinvestigation of Correlation between Rate and Ionization Potential
    Cheal Kim, Teddy G. Traylor, and Charles L. Perrin. J. Am. Chem. Soc. 1998, 120, (37), 9513-9516. DOI: 1021/ja981531e
    An interesting paper that describes the development of a kinetic method for measuring the rate of epoxidation of various alkenes with m-CPBA.
  7. Experimental Geometry of the Epoxidation Transition State
    Daniel A. Singleton, Steven R. Merrigan, Jian Liu, and K. N. Houk. J. Am. Chem. Soc. 1997, 119, (14), 3385-3386. DOI: 1021/ja963656u
    Combined experimental and theoretical studies of the epoxidation transition state, showing that both C-O bond forming events are nearly synchronous.
  8. The mechanism of epoxidation of olefins by peracids
    V. G. Dryuk. Tetrahedron. Volume 32, Issue 23, 1976, 2855-2866. DOI:10.1016/0040-4020(76)80137-8
    An account of the author’s work on kinetic studies of the epoxidation of olefins with peracids in order to determine the exact mechanism.


Comment section

36 thoughts on “Reagent Friday: OsO4 (Osmium Tetroxide)

  1. You can make the use of OsO4 catalytic if you throw in a sacrificial oxidant, N-morpholine oxide (NMO). I’ve had several lab mates use catalytic NMO without incident.

    1. Oh yeah. My point (perhaps not so well made) was that undergraduate teaching laboratories are unlikely places to learn how to use OsO4. But maybe there are places out there who do?
      Your point brings up another question – I”m wondering how many instructors include NMO when they teach the dihydroxylation reaction.

      1. I’ve worked with students from dozens of schools, and I can’t find another of an example of an instructor who does (although Jim Tour teaches cat. OsO4 and H2O2). You, my good man, are one of the very few! Good on you.

      2. They do where I go to college (Uni. of Minnesota). My prof mentioned using NMO because OsO4 is ridiculously expensive, and NMO turns it into a catalyst so you don’t need as much. She failed to mention the burning out the eyes part, though.

          1. NMO is in McMurray, 8th Edition (used by 1 of 3 sections at SUNY Geneseo).

    2. Ohio State Organic chem teaches using it and Miami University of Ohio

      example problem from class..

      an alkene —–OSO4 (cat.), NMO——> enantiomers

      (side note: if possible adding an image attachment option to the comments)

  2. Wow, I had no idea it’d ever been used on that scale in a synthesis! Unfortunately for those guys the Upjohn catalytic procedure wasn’t reported until 20 years later. I seem to remember that Kumamoto’s synthesis of methyl-kinamycin C and Corey’s neotripterifordin also use it stoichiometrically, although not on anywhere near that scale. I once saw the selective dihydroxylation of one bond in a 1,4-cyclohexadiene reported in a very old Tet. Lett. using stoichiometric OsO4. When I tried it with NMO as the terminal oxidant aromatisation was a major problem so I changed my route. I never had the courage to try with the 1.1 equiv. reported so I’ll always wonder if it would have worked. If nothing else, OsO4 is also damned expensive (~300$/g from Aldrich).

    At the university where I currently am (I can tell you it’s in the UK, if you couldn’t guess from my spelling) 3rd year undergrads get to do Sharpless AD, although obviously that’s with potassium osmate, which is far less volatile/nasty. Still, they do generate OsO4 during the reaction, and they only have to quench it wrong (which is not impossible) for potentially bad things to happen. I get very nervous when this experiment runs.

    1. Wow! Sharpless AD in 3rd year? That’s fantastic. The AD-mix makes it pretty easy I guess. Kudos to your school. In the “advanced organic chemistry” labs I’ve been in or TA’d, there’s always seemed to be a fine, 30-year or more patina of dust on the procedure we were using. Nothing wrong with that per se, but it didn’t give you the exciting feeling of doing something cutting edge.

  3. Why isn’t the stereoisomer for the cyclo hexene drawn (side question)? I feel like the answer’s at the tip of my tongue but I can’t quite get it.

      1. Since one of those reactions gives a mix of products (enantiomers) while the other gives only one product, the reaction in general is stereoselective?

        1. Whether you get one product or a mixture of enantiomers/diastereomers will depend on the alkene you start with.

          Dihydroxylation of ethene would only give one product, for example.

          The reaction itself is stereoselective. Starting with cyclohexene you get one product – cis 1,2-cyclohexane diol, and none of the trans. If you obtained a random *mixture* of cis- and trans- 1,2-diols from cyclohexene, then it would not be stereoselective.

          This is going beyond what you asked, but not only is this reaction stereoselective, it is stereospecific.
          Here’s why.
          Take two alkenes that are diastereomers. cis but-2-ene and trans but-2-ene.
          Now treat each with OsO4.
          The cis but-2-ene will give a single product (S,R)-2,3-butanediol (meso).
          The trams but-2-ene will give a racemic mixture of diols. (S,S)-2,3-butanediol and (R,R)-2,3-butanediol. These are each diastereomers of (S,R)-butanediol.

          So two diastereomeric alkenes give two diastereomeric products. That’s the IUPAC definition of stereospecific.

  4. Hi, just wondering in what cases does OsO4 fail? Certain alkenes? What about enones (I’ve seen that it does some enones but wondering if some cases would fail)? And how are the reactivities between OsO4 and K2OsO4 differ, besides the latter having hydrates and not useful for moisture sensitive reactions? Thanks!

    1. When the reaction is done, “H2O2” re-oxidizes the OsO2(OH)2 back to OsO4. It’s a reoxidant, which allows OsO4 to be used catalytically. A more common reagent for this purpose is N-methyl morpholine N- oxide (NMO)

  5. Hey thanks for all your help and dedication to furthering education. Really appreciate your help with making these pages. Between this and the people at Clutchprep I’m acing organic chem and can’t wait for orgo II, bio chem, and pharmacy school next august.
    Cheers :)

  6. Hi James,
    How exactly does the H2O2 hydrolyze the intermediate 5-member ring? Does it donate a proton onto the Oxygen involved in the C-O bond? If so, why would the oxygen want to form that O-H bond instead of remaining with the rest of the ring?

  7. Hey James,
    Reaction of alkenes with cold KMnO4 and OsO4 results in d production of cis -Diol .is there any reaction for production of trans-diol????

  8. James I am looking to recover osmium in a mixture of strong acids at high temperature from a HNO3, H2SO4, HCl digestion. Had no luck complexing it with thiourea since acids + heat = destroyed complexing agent. I’m basically looking to prevent OsO4 formation and recover low level Os spikes. Any help would be greatly appreciated. Regards

  9. I do not believe that products in Example 1 are meso compounds that result from the syn addition. They certainly look like the products of anti-addition. Both -OH groups should be either wedged or dashed, if added on the same side. Here they are the same but on different sides. If you rotate, they definitely look like the products from anti-addition (the example on hydroxylation of a linear alkene).

    1. Hi, it doesn’t say that they are meso compounds in this specific example, it says they are a mixture of enantiomers.

      However, what about example 2?

  10. Dear James

    If we have a molecule which contain both alkene and aldehide’and we want to prepare diol. will osmium tetraoxide oxidize the aldehide? If yes can you suggest me how to get the diol without oxidizing the akdehide?

    1. Hi Ptachia – I would not do a dihydroxylation with an unprotected aldehyde. Too many things can go wrong. Either keep it at the protected alcohol stage and then oxidize up afterwards, or protect the aldehyde as an acetal and then perform the dihydroxylation.

  11. Dear Dr

    I think I found a way how to this, without protecting the aldehyde. I would appreciate to get your opinion

    Stage 1: reaction with peroxide to get epoxide
    Stage 2: acidificaion

    1. Without knowing the structure, it’s hard to say. Is it an alpha, beta unsaturated aldehyde? Epoxidation may work, but then again peroxide may end up oxidizing your aldehyde.

      Aldehydes are some of the most sensitive functional groups to oxidation and other side reactions. I would generally suggest they are protected unless you have some strong reason for believing it would not be affected by the OsO4 or its co-oxidant.

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.