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Organic Reagents

By James Ashenhurst

Reagent Friday: Raney Nickel

Last updated: January 29th, 2020 |

Raney Nickel And The Desulfurization Of Thioacetals + Hydrogenation Of Alkenes (and Alkynes)

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

raney-nickel.

Named reagents have a slightly mysterious air to them, conjuring up (for me, anyway) the image of a lone scientist working long hours for an elusive goal, until they finally have that “Eureka” moment. In this vein, while “Rearden metal” may solely be a work of fiction, “Raney Nickel” is very real. Raney nickel is an alloy of aluminum and nickel, which has subsequently had much of the aluminum removed through a leaching process with sodium hydroxide (NaOH). The remaining alloy has a very high surface area and also contains hydrogen gas (H2) adsorbed on the nickel surface.

Reduction Of Sulfur Groups (Dithianes) To Alkanes With Raney Nickel 

What it’s used for: Like palladium on carbon (Pd/C) and platinum on carbon (Pt/C), Raney nickel can be used for the hydrogenation of alkenes and alkynes. But what Raney nickel is used most for is its unusual property of reducing C-S bonds to C-H bonds. It’s this second application that can make this reagent uniquely useful. When combined with the formation of a thioketal from a ketone, this can serve as an alternative means of converting ketones to alkanes (just like the Wolff-Kishner reaction). For a real-life application of this reagent in the synthesis of erythromycin by Nobel Laureate R.B. Woodward, see the great discussion by B.R.S.M. here. Added 2019: We miss you BRSM!

removal-of-sulfur-containing-groups-with-raney-nickel-and-conversion-of-thioketals-to-alkanes

As A Hydrogenation Catalyst

Here’s the second application of this reagent – as a catalyst for hydrogenation. Note that in this case we don’t necessarily need to add hydrogen gas (although it helps) – Raney nickel is usually obtained in its “activated” form, where the hydrogen is already adsorbed onto it.

hydrogenation-of-alkenes-to-alkanes-with-raney-nickel

How it works: “For our purposes” (love this phrase) it’s not so important exactly how Raney nickel works. There’s something mysterious about it: the aluminum is crucial for its activity, and the metal doesn’t behave the same once it’s been completely removed. To be honest I plead ignorance on exactly how Raney nickel works its desulfurizing magic, although the catalytic hydrogenation process is likely similar to those of Pd/C and Pt/C.

Real life tips: Perhaps a better description for Raney nickel is “Raney Mud”, because that’s what it looks and feels like. Raney nickel resembles a kind of mud or wet clay, and is actually stored in water. Determining the exact molar ratio of Raney nickel to use is also something of an art – rather than “moles”, typical procedures call for “teaspoons” [I’m not sure I’m aware of any other reagent that calls for this unit of measurement!] After dispensing (but before placing in the reaction vessel) the metal is then rinsed with water (to remove aluminum salts and ensure neutral pH). This can be something of a dicey prodedure since Raney nickel will spontaneously combust in air when traces of moisture are removed. Excess Raney nickel on benchtops, spatulas, weighing paper, etc. should be (carefully) destroyed with acid. There’s nothing like setting up your reaction and then, out of the corner of your eye, noticing little flames coming from traces of Raney nickel on your weighing paper.

Disclaimer: this paragraph should not suffice as training in the use of this reagent, which can be extremely dangerous in the wrong hands. Don’t be stupid.

P.S. You can read about the chemistry of this reagent and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF. The Reagents App is also available for iPhone, click on the icon below!

 Image credit

(Advanced) References And Further Reading

  1. CYCLIC KETONES FROM 1,3-DITHIANE: CYCLOBUTANONE
    D. Seebach, A. K. Beck
    Org. Synth. 1971, 51, 76
    DOI: 10.15227/orgsyn.051.0076The method of reducing a carbonyl group to a methylene via a thioketal is known as a Mozingo reduction, and this can be done with Raney-Ni. This has applications in organic synthesis, as shown in the following references:
  2. A One-Pot Formal [4 + 2] Cycloaddition Approach to Substituted Piperidines, Indolizidines, and Quinolizidines. Total Synthesis of Indolizidine (−)-209I
    Shanghai Yu, Wei Zhu, and, and Dawei Ma
    The Journal of Organic Chemistry 2005 70 (18), 7364-7370
    DOI:     1021/jo051080y
    The last step in the total synthesis of the title compound involves reduction of the 1,3-dithiolane with Raney Ni.
  3. C−H Acetoxylation‐Based Chemical Synthesis of 17 β‐Hydroxymethyl‐17 α‐methyl‐18‐norandrost‐13‐ene Steroids
     Alaksiej L. Hurski, Maryia V. Barysevich, Tatsiana S. Dalidovich, Marharyta V. Iskryk, Nastassia U. Kolasava, Dr. Vladimir N. Zhabinskii, Prof. Dr. Vladimir A. Khripach
    Chem. Eur. J. 2016, 22 (40), 14171-14174
    DOI: 10.1002/chem.201602957
    Steps 30 -> 32 in this synthesis involve a Mozingo reduction.
  4. Desulfurization of Thioketals into Methylene and Methyl Derivatives: Nickel or not Nickel?
    Guangkuan Zhao, Ling‐Zhi Yuan, Mouad Alami, Olivier Provot
    Chemistry Select 2017, 2 (33), 10951-10959
    DOI:     1002/slct.201702370
    This modern review outlines the wide variety of methods that are now available for reduction of thioacetals.This thioacetal methodology was first discovered by Nobel Laureate Prof. E. J. Corey (Harvard) and Prof. Dieter Seebach (ETH Zurich) while Prof. Seebach was a postdoc in Prof. Corey’s group. Profs. Corey and Seebach coined the term ‘umpolung’ to describe the ‘reversal of polarity’ that is enabled by this method. Normally acyl groups are thought of as electrophilic (e.g. acyl cation equivalents in Friedel-Crafts acylation), but this allows one to develop syntheses based around acyl anion equivalents.
  5. Carbanions of 1,3‐Dithianes. Reagents for C-C Bond Formation by Nucleophilic Displacement and Carbonyl Addition
    E.J. Corey, D. Seebach
    Angew. Chem. Int. Ed. 1965, 4 (12), 1075-1077
    DOI: 10.1002/anie.196510752
  6. Synthesis of 1,n‐Dicarbonyl Derivates Using Carbanions from 1,3‐Dithianes
     J. Corey, D. Seebach
    Angew. Chem. Int. Ed. 1965 4 (12), 1077-1078
    DOI: 10.1021/anie.196510771
00 General Chemistry Review
01 Bonding, Structure, and Resonance
02 Acid Base Reactions
03 Alkanes and Nomenclature
04 Conformations and Cycloalkanes
05 A Primer On Organic Reactions
06 Free Radical Reactions
07 Stereochemistry and Chirality
08 Substitution Reactions
09 Elimination Reactions
10 Rearrangements
11 SN1/SN2/E1/E2 Decision
12 Alkene Reactions
13 Alkyne Reactions
14 Alcohols, Epoxides and Ethers
15 Organometallics
16 Spectroscopy
17 Dienes and MO Theory
18 Aromaticity
19 Reactions of Aromatic Molecules
20 Aldehydes and Ketones
21 Carboxylic Acid Derivatives
22 Enols and Enolates
23 Amines
24 Carbohydrates
25 Fun and Miscellaneous
26 Organic Chemistry Tips and Tricks
27 Case Studies of Successful O-Chem Students

Comments

Comment section

39 thoughts on “Reagent Friday: Raney Nickel”

  4. I believe the reaction you show for reducing a ketone to a methylene derivative is formally known as the Mazingo Reaction. It might be useful info to add.

    Speaking of which, is there a reason to NOT use the Mazingo Reaction, in favor of either the Wolff-Kishner or Clemmensen reductions?

    Reply

  5. I have a molecule with two functionalities to reduce. Nitro to amine & double bond to single. Have a halogen too. Do you think Ra-Ni will be good or if some one suggest any suitable procedure?
    Thanks

    Reply

  6. Can raney nickel reduce polar multiple bonds such as aldehydes or ketones?
    And can raney nickel reduce conjugated(in conjugation with aldehyde or ketone)non polar multiple bonds?

    Reply

  7. Hello,
    You did mention some ways to dispose of the Ra-Ni. My question is regarding the lifetime of the Ra-Ni… as in, is it reusable? Or can it only be used once as a catalyst in a hydrogenation reaction in the presence of H2? When destroyed, does Ra-Ni end up in waste streams? I understand that certain transition metals in aqueous solution can be very toxic.
    Thank you for your time.

    Reply

    1. When I used it personally it did not appear to be reusable in any way. I ended up with green wastewater after destruction of excess reagent with acid. Nickel is not nearly as bad as chromium, but proper waste procedures should be followed.

      Reply

    1. No, acetals are inert to reduction. One trick with Raney nickel, however, is that it is quite acidic if it isn’t washed thoroughly with distilled water. If an acetal is being reduced by Raney nickel it is because the acetal is being hydrolyzed by acid and the resulting aldehyde is being reduced to an alcohol.

      Reply

  12. Hi! that is great. But can ı ask a question? Can we use raney nickel with alkynes? if we use , will product be cis or trans alkene or alkane? And LDA can do alcohol?

    Reply

  13. Hi! Wonderful work, and Thank You very much. I’ve got one small question though. Is reduction using Nickel as more effective than when using Platinum catalyst? I’ve seen Nickel not only reducing double bonds and triple bonds to single ones but also reducing aldehydes and ketones to alcohol. I don’t think Platinum reduces ketones or aldehydes to alcohol. Is this true?

    Reply

    1. It depends on whether you are asking about some reaction in your course or if you’re actually doing this on a practical level. I see some courses where instructors say that Ni will reduce carbonyls while Pd will not, and others where there is no distinction. For more information I suggest you look up Pd and Ni in Encyclopedia of Reagents for Organic Synthesis, or March’s Advanced Organic Chem. The short answer is, given enough pressure of H2, even Pd/C will reduce carbonyls.

      Reply

  14. Hi James
    the amount of adsorbed hydrogen depends on the grade of nickel used – Johnson Matthey have at least 30 and more if you ask nicely. Grace (who own “Raney” as it’s a trademark) have their own grades again. Each has their own merits.
    Even though desulfurisation is catalytic, an excess of nickel is usually required.
    I’ve had some nice selectivity enhancements through using the aluminium-nickel alloy with the substrate and controlled addition of NaOH – this makes Raney nickel in situ and generates hydrogen simultaneously, hence why controlled addition helps. Add the NaOH too fast and you lose too much hydrogen and gain a large exotherm!
    In my experience the Raney slurry is usually basic due to the process.
    Cheers

    Reply

  15. There is a reaction from the literature (angew. chem. internat. edit. vol. 6 (1967) P864) to reduce nitro group to amino group and a intramolecular cyclyzation happened.

    The question is about the pressure used in the condition (Raney nickel in methanol/H2/100 atm/RT). What’s that pressure for?

    Reply

    1. The higher the pressure of H2, the faster the reaction will occur. Essentially you’re adding more “equivalents” of H2 and forcing the adsorption of H2 on to the active sites of the metal, speeding up the reaction (which occurs on the metal surface)

      Reply

  18. Is there a source for solid Ra-Ni screen or plate material in small amounts?
    Or is this even the best cathode material for a hydrogen gas generator?

    Reply

  19. When one does a hydrogenolysis with Raney-Nickle, is it valid to keep the reaction under a hydrogen environment in order to shift the adsorption-reaction equillibrium towards the hydrogenated product? This I have done and wonder if it also applies to the palladium/carbon catalyst.

    Reply

    1. I’ve only used Ra-Ni on a few occasions (for hydrogenation) but I used it under an atmosphere of H2. In theory it might be possible to run hydrogenations without it due to the fact that Ra-Ni has adsorbed hydrogen. With Pd/C there is no adsorbed hydride, so you must use an atmosphere of H2, or alternatively use a slightly different source of hydride, like ammonium formate.

      Reply

    1. Reduce with Pt/C or Pd/C under high pressure of hydrogen. Go to March’s Advanced Organic Chemistry for literature links and other suggestions.

      Reply

  22. Thanks for the link (and reminding me that my ex still has my copy of Atlas Shrugged)! I also have no idea exactly how desulfurisation occurs, and I’m totally fine with that.

    Reply

  23. From Organic Syntheses, Coll. Vol. 10, p.603 (2004); Vol. 79, p.93 (2002), a good approximation of the “best practices” procedure for accurately weighing out small amounts of Raney Ni:

    “The Raney nickel (WR Grace Grade 28) was obtained as a 50 wt% aqueous slurry from Strem Chemicals Inc. The mass of the Raney nickel was determined by the following procedure:4 The weight, in grams, of a 500-mL volumetric flask filled with deionized water was recorded (Mass A). A portion of the water was removed and replaced with the Raney Nickel slurry. The remaining volume was filled with deionized water and reweighed (Mass B). The amount of Raney nickel , in grams, was calculated using the equation Amt. = 1.167(Mass B − Mass A), where 1.167 accounts for the volume of water displaced by the Raney nickel catalyst with an average density of 7.00 g/mL. However, prior to transferring to the flask, the excess water was decanted from the material. Small spills of Raney nickel slurry were transferred with a wet Kimwipe to a waste container containing water. The ethanol was undenatured.”

    Reply

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