Reduction with Na/EtOH

Question

I wish to know the reduction of functional groups such as:

1. Acid Chloride
2. Nitro Compound
3. Acid Amide
4. Conjugated Alkene
5. Alkyne
6. Primary/Secondary/Tertiary Alkyl Halide

I am not sure whether the given reagent reduces these functional groups or not. Any kind of help along with the products of the reactions would be helpful.

This question is NOT similar to previous questions asked in the website as I have listed different functional groups.

Answer 1

The reduction method using absolute ethanol and sodium metal is a named reaction called Bouveault–Blanc reduction, which is a chemical reaction used to reduce organic ester to corresponding primary alcohols. The reaction is founded by French scientists, Louis Bouveault and Gustave Louis Blanc in 1903 and hence the name. The mechanism of the reduction is proposed as following in Wikipedia and here:

The advantage of Bouveault–Blanc reduction method is a modified version of it has been developed for the synthesis of $\alpha,\alpha$-dideuterio alcohols from carboxylic acid esters (Ref. 2):

Since as it is shown in the mechanism, the corresponding aldehyde to the ester is the intermediate, which undergoes further reduction to corresponding primary alcohol, it is safe to say any aldehyde and ketone can be reduced by this system to corresponding primary and secondary alcohols, respectively.

As Waylander correctly suggested, acid chloride will reacted first to give ethyl ester, which can undergoes Bouveault-Blanc reduction to give corresponding alcohol. The byproduct of esterification, $\ce{HCl}$ would be act as a catalyst to the reduction process (Ref. 3):

However, for acid amide, there is possibility for $\ce{C-N}$ cleavage during the reduction process (when using original $\ce{Na/EtOH}$ conditions) to give corresponding alcohol instead of amine. Yet, you can modified the conditions to achieve corresponding amine as nicely demonstrated in Ref. 4:

As Waylander suggested in his answer elsewhere, I can't find any reference for reduction of nitro groups by Bouveault-Blanc reduction conditions (read this article). However, reduction of nitrobenzene to aniline has been reported using sodium sulfide in aqueous ethanol (Ref. 5). Alternatively, an amine can be achieved by the reduction of alkyl nitriles under Bouveault-Blanc reduction condition (Ref. 6):

There is no carbinyl groups in nitriles so there is no competition to Cleve $\ce{C-N}$ vs $\ce{C-O}$ in this reduction (thus need no modification to the condition) so that amine is the only product possible. Although this method need nomodification, use of solvents such as hexane and THF with $\pu{6 eq.}$ of $\ce{EtOD_{d_1}}$ has given better yields.

The reduction of organic halide doesn't need $\ce{EtOH}$ in the system with $\ce{Na}$ metal (e.g., Würtz reaction). For instance, benzyl halide with $\ce{Na/THF}$ gives bibenzyl as the product in good yield (Ref. 7):

Similarly, styrene and its substituted derivative with $\ce{Na/THF}$ give 1,2-phynylethanes as the product in good yield as well (Ref. 8):

Based on the quencher used you achieve either 1,2-diarylethane (quencher: $\ce{H2O}$) or 1,2-diarylcyclopropane (quencher: 1,3-dichloropropane ($\ce{CH2(Cl)CH2CH2Cl}$)).

About reduction of compounds with conjugated Alkene moiety: In addition to all of above reduction reactions under Bouveault−Blanc Reduction conditions, it is worth noting that Ref. 1 reported reduction of methyl cinnamate, which is an $\alpha,\beta$-unsaturated ester has given 3-phenylpropanol as the only product reducing both carbonyl and double bond moieties of the cinnamate (95% yield). The reduction of methyl 4-methoxycinnamate $(\ce{(4-MeO)Ph-CH=CHC(=O)OMe})$, which is also an $\alpha,\beta$-unsaturated ester has given 3-(4-methoxyphenyl)propanol $(\ce{(4-MeO)Ph-CH2CH2CH2OH})$ as the only product reducing both carbonyl and double bond moieties of the initial cinnamate (98% yield).

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References:

1. See Reference 1b in this article, which gives safer conditions to original Bouveault−Blanc Ester Reduction as well: Brian S. Bodnar and Paul F. Vogt, “An Improved Bouveault−Blanc Ester Reduction with Stabilized Alkali Metals,” J. Org. Chem. 2009, 74(6), 2598–2600 (DOI: https://doi.org/10.1021/jo802778z).
2. Minhui Han, Xiaodong Ma, Shangchu Yao, Yuxuan Ding, Zihan Yan, Adila Adijiang, Yufei Wu, Hengzhao Li, Yuntong Zhang, Peng Lei, Yun Ling, and Jie An, “Development of a Modified Bouveault–Blanc Reduction for the Selective Synthesis of $\alpha,\alpha$-Dideuterio Alcohols,” J. Org. Chem. 2017, 82(2), 1285–1290 (DOI: https://doi.org/10.1021/acs.joc.6b02950).
3. Hengzhao Li, Mengqi Peng, Lijun Wang, Tingting Jiang, Xinxin Li, Yijing Fu, Zhaonong Hu, and Jie An, “Single Electron Transfer Reductive Deuteration of Acyl Chlorides for the Synthesis of Deuterated Alcohols with a High Deuterium Atom Economy,” Org. Lett. 2024, 26(3), 719–723 (DOI: https://doi.org/10.1021/acs.orglett.3c04155).
4. Bin Zhang, Hengzhao Li, Yuxuan Ding, Yuhao Yan, and Jie An, “Reduction and Reductive Deuteration of Tertiary Amides Mediated by Sodium Dispersions with Distinct Proton Donor-Dependent Chemoselectivity,” J. Org. Chem. 2018, 83(11), 6006–6014 (DOI: https://doi.org/10.1021/acs.joc.8b00617).
5. O. J. Cope and R. K. Brown, “The Reduction of Nitrobenzene by Sodium Sulphite in Aqueous Ethanol,” Canadian Journal of Chemistry 1961, 39, 1695–1710 (DOI: https://doi.org/10.1139/v61-217).
6. Yuxuan Ding, Shihui Luo, Adila Adijiang, Hongye Zhao, and Jie An, “Reductive Deuteration of Nitriles: The Synthesis of $\alpha,\alpha$-Dideuterio Amines by Sodium-Mediated Electron Transfer Reactions,” J. Org. Chem. 2018, 83(19), 12269–12274 (DOI: https://doi.org/10.1021/acs.joc.8b01730).
7. Bubwoong Kang, Tatsuro Imamura,and Tetsuya Satoh, “Sodium dispersion-mediated reductive dimerization of benzylic halides for symmetrical bibenzyls: Column-free applications to natural products,” Tetrahedron Green Chem. 2024, 4, Article #: 100052 (6 pages) (DOI: https://doi.org/10.1016/j.tgchem.2024.100052).
8. Ugo Azzena, Giovanna Dettori, Caterina Lubinu, Alberto Mannu, and Luisa Pisano, “Reductive metalation of 1,2-diaryl-substituted ethenes: synthetic applications,” Tetrahedron 2005, 61(36), 8663-8668 (DOI: https://doi.org/10.1016/j.tet.2005.06.108).

Answer 2

Acid chloride in the presence of EtOH is going to generate ethyl esters, however it is well established that esters are reduced by sodium metal/EtOH so overall you will get reduction of the acyl chloride to alcohol. This is the Bouveault Blanc reduction.

Amides may be reduced to amines as noted in this SE answer 115431

To the best of my knowledge alkenes and alkynes are not reduced by sodium/ethanol. Sodium/liquid ammonia is a different case.

Despite the claims of SE answer 132025 here, I can find no examples of Na/EtOH reduction of nitro groups, and Hudlicky's Reductions in Organic Chemistry full book here, my go to book on the subject does not mention it.

Alkyl halides also appear to not be reduced by sodium/EtOH. I think it likely that that the sodium ethoxide produced will either give elimination products or ethyl ethers.

I commend the Hudlicky book to your attention for any questions on the reduction of functional groups.