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Predicting the Product

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Reduction of 3,6-diazahomoadamantan-9-ones (Ia–g) as described by Kuznetsov et al.

Depending on the pathway, the methylene product or azine product is formed.

This study explores the Wolff–Kishner reduction of 3,6-diazahomoadamantan-9-ones (Ia–g), yielding either reduced amines (IIIb–e, g) or azine dimers (IVa–d) depending on substitution. While substituted hydrazones (IIb–e, g) undergo clean reduction to the corresponding amines, the unsubstituted hydrazone (IIa) instead forms a stable azine (IVa). The work establishes a reliable synthetic route to these products and confirms their structures using IR, ESR, and mass spectrometry.
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Schematic representation of the Wolff–Kishner reduction of 3,6-diazahomoadamantan-9-ones (Ia–g) as described by Kuznetsov et al.

This reaction yielded 3,6-diazahomoadamantanes (IIIb–e, g) from substituted ketones, while the unsubstituted analog (IIa) formed azine dimer IVa upon thermal decomposition.

In this study, the Wolff–Kishner reduction began with the formation of hydrazones by reacting substituted diazahomoadamantanones (Ia–e, Ig) with excess hydrazine hydrate.These hydrazones were then subjected to thermal decomposition by heating them with powdered potassium hydroxide at high temperatures (220–240 °C) for 2–3 hours. Upon cooling, the mixtures were extracted with ether, and the crude products were purified either through sublimation or recrystallization.This sequence effectively reduced the ketone group to a methylene yielding stable 3,6-diazahomoadamantanes.
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Identifying Reagents and Reaction Conditions

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Identify the target carbonyl group and subsequent steps

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Identify the General Scheme

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Directly apply the scheme to determine product

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Mechanism for Carbonyls

This section is a brief overview on how to perform the mechanism for both aldehydes and ketones using the paper from above. Hero Light We know the scheme for this reaction and the product. Lets do the mechanism now.
For the mechanism, we only selectively reduce the Ketone. We not do anything to the rest of the molecule. R1 and R2 represents the rest of the molecule.
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Ketone to Hydrazone Conversion

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  1. Hydrazine’s terminal nitrogen attacks the carbonyl carbon, forming a tetrahedral intermediate.
  2. A proton shifts from the N–H⁺ to the alkoxide, yielding a neutral alcohol.
  3. Base deprotonates the hydroxyl group, facilitating loss of water and forming the C=N double bond.
  4. Hydrazone is formed. (C=NNH₂).
Hero LightWe are now half-way through with the mechanism and scheme.
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Hydrazone to Methylene Product

Hero LightThe Hydrazone is deprotonated by hydroxide and reprotonated by water. Eventually, this leads to removal of a N2 group. Lastly, a final protonation by water yields the Methylene (alkane) product.
Hero LightWe are now fully completed with the mechanism and the scheme is completed.

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Summary

The reaction entry summary. Find the general scheme and full summarized mechanisms here.

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General Scheme

This section briefly summarizes what can and cannot undergo reactions. Hero Light
  • Wolff-Kishner uses Hydrazine (H₂N–NH₂), a strong base (KOH or KOtBu), and heat
  • Carbonyls are converted into a methylene (–CH₂) group (alkane)
  • All reactions, follow a general scheme:
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General Mechanism

This section briefly summarizes steps to find the product and perform the mechanisms. Quick steps to finding the product for any carbonyl
  1. Identify the reagents.
  2. Identify the target carbonyl to be reduced.
  3. Selectively convert the carbonyl, keep the rest of molecule the same.
  4. Always remember the general scheme.
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Always remember to repeatedly practice your mechanisms and getting your reagents correct. Take advantage of our materials and/or keep practicing on a whiteboard or paper until you get it right every single time.

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References

[1] Kishner, N. Wolff–Kishner reduction; Huang–Minlon modification. J. Russ. Phys. Chem. Soc. 1911, 43, 582–595. ↩

[2] Wolff, L. Chemischen Institut der Universität Jena: Methode zum Ersatz des Sauerstoffatoms der Ketone und Aldehyde durch Wasserstoff. [Erste Abhandlung]. Justus Liebigs Ann. Chem. 1912, 394, 86–108. https://doi.org/10.1002/jlac.19123940107 ↩

[3] Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. ↩

[4] Verma, D. K.; Dewangan, Y.; Verma, C. Reactions of Aldehydes and Ketones. In Handbook of Organic Name Reactions; Verma, D. K., Dewangan, Y., Verma, C., Eds.; Elsevier: 2023; pp 155–241. ↩

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[5] Kuznetsov, A. I.; Vladimirova, I. A.; Serova, T. M.; Moskovkin, A. S. Heteroadamantanes and Their Derivatives. 17. Wolff–Kishner Reduction of 3,6-Diazahomoadamantan-9-ones. Chem. Heterocycl. Compd. 1992, 28, 551–555. https://doi.org/10.1007/BF00475255 ↩