Sodium cyanoborohydride
[CAS 25895-60-7]

Identification

• Classification: Inorganic chemical industry >> Inorganic salt >> Boride, borate and perborate
• Name: Sodium cyanoborohydride
• Synonyms: Sodium cyanotrihydroborate
• Molecular Formula: CH₃BNNa
• Molecular Weight: 62.84
• CAS Registry Number: 25895-60-7
• EC Number: 247-317-2
• SMILES: [BH3-]C#N.[Na+]

Properties

• Density: 1.2 g/mL (Expl.)
• Melting point: 242 °C (Decomposes) (Expl.)
• Flash point: 70 °C (Expl.)
• Solubility: Soluble in water, THF, methanol (Expl.)

Safety Data

• Hazard Symbols: GHS02;GHS05;GHS06;GHS09 DangerGHS02
• Risk Statements: H228-H300-H310-H314-H318-H330-H400-H410
• Safety Statements: P210-P240-P241-P260-P262-P264-P264+P265-P270-P271-P273-P280-P284-P301+P316-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P354+P338-P316-P317-P320-P321-P330-P361+P364-P363-P370+P378-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H300
Acute toxicity	Acute Tox.	2	H330
Skin corrosion	Skin Corr.	1B	H314
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Acute toxicity	Acute Tox.	2	H310
Flammable solids	Flam. Sol.	1	H228
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	1	H310
Flammable solids	Flam. Sol.	2	H228
Skin corrosion	Skin Corr.	1C	H314
Substances or mixtures which in contact with water emit flammable gases	Water-react.	1	H260
Acute toxicity	Acute Tox.	1	H330
Substances or mixtures which in contact with water emit flammable gases	Water-react.	2	H261
Acute toxicity	Acute Tox.	1	H300

• Transport Information: UN 3179

chemBlink Chemical Story

Sodium cyanoborohydride, CAS 25895-60-7, is a selective borohydride reducing agent best known for its role in reductive amination, one of the most useful methods for forming carbon-nitrogen bonds in organic and medicinal chemistry. Its formula is NaBH₃CN. The reagent resembles sodium borohydride, NaBH₄, but replacing one hydrogen attached to boron with a cyano group substantially changes its reducing behavior.

This difference in reactivity is the key to the reagent's usefulness. Sodium borohydride readily reduces many aldehydes and ketones to alcohols. Sodium cyanoborohydride is generally milder under the conditions used for reductive amination and can preferentially reduce imines and protonated imines, or iminium ions, while leaving much of the starting carbonyl compound unreacted.

That selectivity makes possible an elegant one-pot transformation. An aldehyde or ketone is mixed with ammonia, a primary amine, or a secondary amine. The carbonyl compound and amine establish an equilibrium involving an imine or iminium species. Sodium cyanoborohydride then reduces the carbon-nitrogen intermediate, producing a new amine.

In simplified form, an aldehyde can undergo the sequence:

R-CHO + R'-NH₂ → R-CH=N-R' → R-CH₂-NH-R'

The important result is that the carbonyl carbon has become bonded to nitrogen. An aldehyde or ketone can therefore be converted directly into a more complex amine without requiring isolation of the intermediate imine.

This chemistry was established as a particularly useful synthetic method by Richard F. Borch, Mark D. Bernstein, and H. Dupont Durst. Their 1971 study of the cyanohydridoborate anion demonstrated its unusual selectivity and showed that aldehydes and ketones could undergo reductive amination with ammonia, primary amines, or secondary amines under mildly acidic to approximately neutral conditions. The transformation subsequently became widely known as Borch reductive amination.

The success of the reagent arises from a subtle electronic modification. The cyano group attached to boron is strongly electron withdrawing. Compared with the BH₄^- ion of sodium borohydride, the BH₃CN^- ion is a less aggressive hydride donor. This apparently modest change allows chemists to distinguish between functional groups that a stronger reducing agent might attack indiscriminately.

Reaction pH is particularly important. Under conditions around mildly acidic to near-neutral pH, an imine can become protonated to form a more electrophilic iminium ion. Sodium cyanoborohydride reduces this species efficiently, while reduction of an unactivated aldehyde or ketone is comparatively slower under appropriately controlled conditions. Selectivity therefore comes from matching reagent strength with the relative reactivity of the species present in solution.

This is an important general principle in synthetic chemistry. The most powerful reagent is not necessarily the most useful reagent. If several reactive groups are present in the same molecule, excessive reactivity can destroy selectivity. A milder reagent may accomplish one desired transformation while leaving other functionality intact.

Reductive amination became particularly important in medicinal chemistry because amines are extraordinarily common in pharmaceuticals and biologically active molecules. The method provides a convenient way to connect a carbonyl-containing fragment with an amine-containing fragment through a new C-N bond. By changing either partner, chemists can rapidly prepare families of related molecules for structure-activity relationship studies.

The reaction is also valuable because primary, secondary, and tertiary amines can be accessed depending on the nitrogen source and substrate. This versatility made sodium cyanoborohydride useful not only in small-molecule synthesis but also in carbohydrate chemistry, polymer modification, and other areas where selective formation or stabilization of carbon-nitrogen bonds is required.

Its chemistry eventually crossed from conventional organic synthesis into biochemistry and biotechnology. Reductive amination can be used to connect aldehyde-containing molecules with amino groups on biomolecules. Sodium cyanoborohydride has consequently been used in protein modification, antibody conjugation, carbohydrate conjugation, and immobilization chemistry.

A typical bioconjugation begins with formation of a reversible Schiff base between an aldehyde and an amino group, such as an amine associated with a protein residue. Reduction converts this reversible linkage into a stable carbon-nitrogen bond. The same fundamental chemistry developed for small organic molecules can therefore be used to connect much larger biological structures.

This application also illustrates why reagent quality and reaction conditions matter. Modern bioconjugation studies have examined free cyanide contamination in commercial sodium cyanoborohydride and its effects on conjugation chemistry. The reagent contains a cyanoborohydride ion and must be handled with particular attention to chemical safety. Strongly acidic conditions can create a risk of releasing highly toxic hydrogen cyanide, so appropriate controls are essential.

Sodium cyanoborohydride therefore represents a useful paradox in organic chemistry. Its importance comes from being less reactive than a closely related reagent. By weakening the reducing power of borohydride, chemists gained greater control over which molecular species would actually be reduced.

That lesson extends far beyond this particular compound. Synthetic chemistry is not simply the search for reagents powerful enough to break or make bonds. Much of sophisticated chemistry depends on discrimination: reacting at one position while ignoring another, transforming one intermediate while allowing another functional group to survive.

Sodium cyanoborohydride became a classic reagent because it performs that discrimination particularly well. Its history demonstrates how changing a single substituent around boron can transform a general reducing agent into a selective tool for building carbon-nitrogen bonds.

References

1. Borch, R. F.; Bernstein, M. D.; Durst, H. D. (1971). "Cyanohydridoborate Anion as a Selective Reducing Agent." Journal of the American Chemical Society, 93, 2897-2904.
https://doi.org/10.1021/ja00741a013

2. Borch, R. F.; Durst, H. D. (1969). "Lithium Cyanohydridoborate, a Versatile New Reagent." Journal of the American Chemical Society, 91, 3996-3997.
https://doi.org/10.1021/ja01042a078

3. Baxter, E. W.; Reitz, A. B. (2002). "Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents." Organic Reactions, 59.

4. Organic Syntheses. "Reductive Amination with Sodium Cyanoborohydride: N,N-Dimethylcyclohexylamine."
https://orgsyn.org/demo.aspx?prep=CV6P0499

5. "Method for Screening Sodium Cyanoborohydride for Free Cyanide Content and Its Impact on Bioconjugation Chemistry." Bioconjugate Chemistry (2025).
https://doi.org/10.1021/acs.bioconjchem.4c00514