Sodium cyanoborohydride

Sodium cyanoborohydride is a salt. The cationic sodium ion, [Na]⁺, interacts with the anionic cyanoborohydride ion, [BH3(CN)]⁻. The anionic component of the salt is tetrahedral at the boron atom.

The electron-withdrawing cyanide substituent draws electron density away from the negatively charged boron; thus, reducing the electrophilic capabilities of the anionic component. This electronic phenomenon causes sodium cyanoborohydride to have more mild reducing qualities than other reducing agents. For example, Na[BH₃(CN)] is less reducing than its counterpart sodium borohydride, containing [BH₄]⁻.

Sodium cyanoborohydride is a mild reducing agent. It is generally used for the reduction of imines. These reactions occur {{cite book |doi=10.1002/047084289X.rs059.pub3 |chapter=Sodium Cyanoborohydride |title=Encyclopedia of Reagents for Organic Synthesis |date=2016 |last1=Hutchins |first1=Robert O. |last2=Hutchins |first2=Marygail K. |last3=Crawley |first3=Matthew L. |last4=Mercado-Marin |first4=Eduardo V. |last5=Sarpong |first5=Richmond |pages=1–14 |isbn=978-0-470-84289-8 }}

Reductive amination, sometimes called the Borch reaction, is the conversion of a carbonyl into an amine through an intermediate imine.{{OrgSynth|author=Richard F. Borch|year=1988|title=Reductive Amination with Sodium Cyanoborohydride: N,N-Dimethylcyclohexylamine|collvol=6|collvolpages=499|prep=CV6P0499}} The carbonyl is first treated with ammonia to promote imine formation by nucleophilic attack. The imine is then reduced to an amine by sodium cyanoborohydride. This reaction works on both aldehydes and ketones. The carbonyl can be treated with ammonia, a primary amine, or a secondary amine to produce, respectively, 1°, 2°, and 3° amines.{{cite journal |author=Richard F. Borch and Mark D. Bernstein and H. Dupont Durst |year=1971 |title=Cyanohydridoborate Anion as a Selective Reducing Agent |journal=J. Am. Chem. Soc. |volume=93 |issue=12 |pages=2897–2904 |doi=10.1021/ja00741a013}}

Aromatic ketones and aldehydes can be reductively deoxygenated using sodium cyanoborohydride.{{cite journal |last1=Box |first1=Vernon G. S. |last2=Meleties |first2=Panayiotis C. |date=1998-09-24 |title=Reductive, selective deoxygenation of acylbenzo[b]furans, aromatic aldehydes and ketones with NaBH3CN-TMSCl |url=https://www.sciencedirect.com/science/article/pii/S0040403998015196 |journal=Tetrahedron Letters |volume=39 |issue=39 |pages=7059–7062 |doi=10.1016/S0040-4039(98)01519-6 |issn=0040-4039}} This means that the carbonyl oxygen is being removed completely from the molecule. Deoxygenation using sodium cyanoborohydride is often done in the presence of trimethylsilyl chloride, or TMSCl.

Sodium cyanoborohydride can be purchased from most chemical suppliers. It can be synthesized by combining sodium cyanide and borane tetrahydrofuran.{{cite journal |last=Hui |first=Benjamin C. |date=October 1980 |title=Synthesis and properties of borohydride derivatives |url=https://pubs.acs.org/doi/abs/10.1021/ic50212a075 |journal=Inorganic Chemistry |language=en |volume=19 |issue=10 |pages=3185–3186 |doi=10.1021/ic50212a075 |issn=0020-1669}}

:{{chem2|BH3*THF + NaCN -> NaBH3CN + THF}}

Since sodium cyanoborohydride is a mild reducing agent, it gives good chemoselectivity for reaction with certain functional groups in the presence of others. For example, sodium cyanoborohydride is generally incapable of reducing amides, ethers, esters and lactones, nitriles, or epoxides.{{cite journal |last=LANE |first=Clinton F. |date=1975 |title=Sodium Cyanoborohydride - A Highly Selective Reducing Agent for Organic Functional Groups |url=http://dx.doi.org/10.1055/s-1975-23685 |journal=Synthesis |volume=1975 |issue=3 |pages=135–146 |doi=10.1055/s-1975-23685 |s2cid=95157786 |issn=0039-7881}} Therefore, it can selectively reduce some functionalities in the presence of others.

Some examples of selective reduction include:

• Reduction of iminium ions in the presence of carbonyls
• Reduction of aldehydes in the presence of ketones and esters.{{cite journal |last1=Paul |first1=Avishek |last2=Shipman |first2=Michael A. |last3=Onabule |first3=Dolapo Y. |last4=Sproules |first4=Stephen |last5=Symes |first5=Mark D. |date=2021-04-15 |title=Selective aldehyde reductions in neutral water catalysed by encapsulation in a supramolecular cage |journal=Chemical Science |language=en |volume=12 |issue=14 |pages=5082–5090 |doi=10.1039/D1SC00896J |issn=2041-6539 |pmc=8179549 |pmid=34163748}}
• Reduction of aldehydes in the presence of thioesters

The selectivity of this reducing agent makes it an important tool in organic synthesis. It allows for specific modifications to be made to complex organic molecules.

Georg Wittig was the first to synthesize a cyanoborohydride by treating lithium borohydride with hydrogen cyanide in 1951. The corresponding compound, sodium cyanoborohydride, was synthesized following a similar rationale by reacting sodium borohydride with hydrogen cyanide.{{cite book |url=https://pubs.acs.org/doi/book/10.1021/bk-1996-0641 |title=Reductions in Organic Synthesis: Recent Advances and Practical Applications |date=1996-08-13 |publisher=American Chemical Society |isbn=978-0-8412-3381-2 |editor-last=Abdel-Magid |editor-first=Ahmed F. |series=ACS Symposium Series |volume=641 |location=Washington, DC |language=en |doi=10.1021/bk-1996-0641.ch001}} The synthesis was later refined to use sodium cyanide and borane in THF making the process safer.

• Sodium triacetoxyborohydride – a milder reductant, but unstable in water
• Sodium borohydride – a stronger, cheaper reductant

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{{Sodium compounds}}

Category:Borohydrides

Category:Sodium compounds

Category:Reducing agents

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