Borohydrides: Reducing Agents in Organic Synthesis

May 29, 2022 | Chemistry, SCIENCE

Borohydrides: An Introduction to Reducing Agents in Organic Synthesis

Borohydrides as reducing agents in organic synthesis are essential compounds in organic and inorganic chemistry. The most essential borohydrides are lithium borohydride and sodium borohydride. Tetrahydroborates are also important in inorganic chemistry academically and industrially.

Borohydrides: An Introduction to Reducing Agents

Borohydrides: An Introduction to Reducing Agents

History of Borohydrides

Alkali metal borohydrides is a class of compounds discovered by Hermann Irving Schlesinger and Herbert C. Brown in 1940. They used diborane to create lithium borohydride. 

2 MH + B2H6 → 2 M[BH4] (M = Li, Na, K, etc.)

Lithium borohydride (LiBH4) is a chemical compound that contains tetrahedral BH4 – ions. It has a molecular weight of 21.75 g/mol with H2 content of 18% by mass. Despite its incredibly high hydrogen content, LiBH4 is relatively stable and only desorbs hydrogen at high temperatures, above the melting point of 540 K.

Currently, these compounds are synthesized by reducing trimethyl borate with sodium borohydride. 

Structure of Borohydrides

Boron has a tetrahedral structure in the borohydride anion and most of its modifications. The reactivity of the BH bonds is affected by the other ligands. Electron-releasing ethyl groups, such as those found in triethylborohydride, make the B-H center extremely nucleophilic. On the other hand, Cyanoborohydride is a weaker reductant due to the electron-withdrawing cyano substituent. The reducing power of the reagent is also affected by the countercation.

Lithium Borohydride

Lithium borohydride is an inorganic compound with the chemical formula LiBH4. It is used as a reducing agent for esters in organic synthesis. Although it is less popular than sodium borohydride, lithium salt has some advantages, including being a stronger reducing agent, completely soluble in ethers, and safer to handle than lithium aluminum hydride. 

Lithium borohydride is highly effective at reducing esters to alcohols and primary amides to amines in methanol and diethyl ether mixtures. The increased reactivity is due to the carbonyl substrate’s polarization caused by the lithium cation’s complexation.

Synthesis of Lithium Borohydride

Lithium borohydride is a white solid that can be prepared by ball-milling sodium borohydride and lithium bromide via the metathesis reaction. 

NaBH4 + LiBr → NaBr + LiBH4

It can also be prepared by reacting boron trifluoride with lithium hydride in diethyl ether:

BF3 + 4 LiH → LiBH4 + 3 LiF

When lithium borohydride reacts with water, hydrogen is produced, which can be used for hydrogen generation.

Sodium Borohydride

Sodium borohydride (NaBH4) is a chemical compound that is also known as sodium tetrahydridoborate and sodium tetrahydroborate.

This white to gray-white powder finds multiple applications in chemistry, both in the laboratory and industrial scale. Sodium borohydride has been tested as a pretreatment for pulping of wood but is too expensive to be commercialized. 

Although it slowly hydrolyzes, it is soluble in alcohols, certain ethers, and water.

At room temperature or lower, it efficiently reduces acyl chlorides, anhydrides, α-hydroxylations, thioesters, and imines. In contrast, it reduces esters slowly and inefficiently with excess reagents but not carboxylic acids or amides at high temperatures.

  1. I. Schlesinger, who led a team looking for volatile uranium compounds, discovered this compound in the 1940s while the findings of this wartime investigation were declassified and published in 1953.

NaBH4 is a salt made up of the tetrahedral anion [BH4]−. They exist in three polymorphs: α, β, and γ. At room temperature and pressure, the stable phase is α-NaBH4, cubic, and has a NaCl-type structure in the Fm3m space group. At 6.3 GPa pressure, the structure varies to tetragonal β-NaBH4 (space group P421c), while at 8.9 GPa pressure, the orthorhombic γ-NaBH4 (space group Pnma) is the most stable.

Synthesis of Sodium Borohydride

Sodium borohydride is a widely-used reducing agent in chemical synthesis. It can be produced commercially by two main methods: the Brown-Schlesinger and Bayer. 

With the Brown-Schlesinger process, sodium borohydride is prepared by treating sodium hydride (produced by reacting Na and H2) and trimethyl borate at 250–270 °C.

B(OCH3)3 + 4 NaH → NaBH4 + 3 NaOCH3

The compound can also be synthesized by using inorganic borates, such as borosilicate glass and borax (Na2B4O7)

Na2B4O7 + 16 Na + 8 H2 + 7 SiO2 → 4 NaBH4 + 7 Na2SiO3

Properties of Some Borohydride Salts

Molecular Weight (g/mol)21.7837.8362.8453.94105.94
Hydrogen Density 18.510.
Density (g/cm3)0.661.071.21.17unknown
Melting Point (°C)280505240 with decomposition585 (under H2)unknown
Solubility in water (g/100 mL at 25 °C)20.955tolerated19decompose
Solubility in Methanol (g/100 mL, 25 °C)decompose (44 in Ethanol)16.4 (at 20 °C)217insolubledecompose
Solubility in Diethyl Ether (g/100 mL, 25 °C)4.3insolubleinsolubleinsolubleN/A
Solubility in Tetrahydrofuran (g/100 mL at 25 °C)22.50.1 (at 20 °C)36insolublehigh (supplied commercially)

Source – 

Potential Applications of Borohydrides

Sodium borohydride is a chemical compound used industrially on a large scale, with a production capacity of 5000 tonnes per year in 2002.

Sodium Borohydride reduces sulfur dioxide to produce sodium dithionite, which helps bleach wood pulp. NaBH4 + 8 NaOH + 8 SO2 → 4 Na2S2O4 + NaBO2 + 6 H2O

Sodium borohydride is used to produce pharmaceuticals such as chloramphenicol, thiophenicol, vitamin A, atropine, scopolamine, and many flavorings and aromas, by reducing aldehydes and ketones.

Light-weight hydrides are good candidates for hydrogen storage in mobile applications due to their high gravimetric hydrogen storage densities. 

Sodium borohydride is used to prevent foxing in old books and documents.

Sodium borohydride (NaBH4) hydrolysis is used as a hydrogen source in automobile applications.

Sodium borohydride reduces cyclic anhydrides to synthesize δ and γ lactones.  

Sodium borohydride is used in the reductive amination of ketones and aldehydes in the presence of an acid catalyst to produce secondary amines.

Sodium borohydride, in conjunction with Raney nickel, can be used in the reduction of aromatic nitro compounds to arylamines.

The borohydride ion can be directly oxidized at an anode surface, providing a higher energy density than hydrogen as the fuel. Alternatively, the borohydride ion’s hydrogen can be kinetically released and fed into a hydrogen-oxygen fuel cell.

Lithium borohydride is used to make other borohydrides, such as aluminum borohydride.

Lithium borohydride reduces aldehydes, ketones, esters, lactones, and epoxides. It catalyzes alkene hydroboration.