CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

Subject Chemistry

Paper No and Title 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module No and Title 16: Reduction by Metal hydrides – Part-I

Module Tag CHE_P9_M16

CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

TABLE OF CONTENTS

1. Learning Outcomes

2. Introduction

3. Reduction methods

3.1 Catalytic resuctions

3.2 Electroreductions and metal reductions

3.3 Hydride and complex hydride reductions

3.4 Reduction with non-metal compounds

3.5 Reduction by organic compounds

4. Hetero atom-carbon multiple bond reduction by metal hydride

4.1 Reduction of Saturated carbonyl compounds

4.1.1 Reduction by Hydride from NaH, NaBH4 and LiAlH4

5. Summary

CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

1. Learning Outcomes

After studying this module, you shall be able to

Familiar with an overview of different categories of reductions

Understand the reduction via hydride transfer by the use of lithium aluminium hydride

and sodium boronhydride reagents.

Differentiate between the selectivity and reactivity of LiAlH4 and NaBH4

Be familiar with other reducing agents viz., sodium cyanoborohydrin,(NaBH3CN),

diisobutylaluminium hydride (DIBAL), diborane (B2H6) and super hydride i.e. Lithium

triethylborohydride (LiEt3BH).

Comprehend how the heteroatom-carbon multiple bond reduction takes place by

metal hydrides for carbonyl compounds

2. Introduction

Oxidation-reduction reactions are vital for biochemical reactions and industrial processes. The

redox reaction includes the electron transfer system in cells and oxidation of glucose in the

human body. Redox reactions are typically used to reduce ores in order to obtain metals to name

a few applications of reduction.

Reduction is generally done either by catalytic hydrogenation or reduction by metal hydrides.

Catalytic hydrogenation is achieved by the addition of hydrogen molecule to the compound under

the influence of a catalyst. The reduction by metal hydrides, on the other hand, is carried out by

transferring hydride ion from the metal hydrides to the substrate. Many reducing agents are

available, but our main focus of study in this module remains metal hydrides.

A hydride is basically an anion of hydrogen (H−, hydride ion) or more commonly, an alloy,

or compound having one or more centres of hydrogen having nucleophilic, reducing or basic

properties. In hydrides, the hydrogen is linked by more electropositive element or group. They are

known for their reducing properties.

The two well- known hydrides are lithium aluminium hydride (LiAlH4) and sodium borohydride

(NaBH4). They contain polar metal-hydrogen linkage because of less electronegativity of

aluminium than that of boron, making them stronger reducing agents. Few other examples of

reducing agents that contain hydrides in them and are commonly used as reducing

agents in chemical synthesis are:

di-isobutyl aluminium hydride (DIBAL) i.e., (i-Bu2AlH)2 where i-Bu

represents isobutyl [-CH2CH(CH3)2].

Sodium cyanoborohydrin (NaBH3CN)

Super hydride i.e., Lithium triethylborohydride (LiEt3BH)

diborane (B2H6)

CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

The reduction reactions achieved by metal hydrides involve carbon–oxygen double bonds,

carbon–nitrogen double bonds, and the carbon–nitrogen triple bond. The mechanism involved

here is very easy as compared to that of the additions to carbon–carbon multiple bonds. As the

double bond of carbon-oxygen and carbon-nitrogen triple bonds are strongly polar due to

electronegative oxygen and nitrogen respectively, the carbon always is at the positive terminal

(except for isocyanides). Hence, the orientation of unsymmetrical addition to these bonds is very

obvious. Nucleophilic attacking species always gets attached at the carbon and electrophilic

species to the oxygen or nitrogen.

Keeping these things in mind, let us discuss the reaction of carbon–oxygen, carbon–nitrogen

double bonds, and the carbon–nitrogen triple bond one by one. Here we shall discuss the hydride

reduction of carbonyl compounds only. The hydride reduction of carboxylic acids, their

derivatives and nitriles shall be discussed in next module.

3. Reduction methods

Reduction in simple terms, indicates the addition of hydrogen to a molecule.

A very common reduction example is the reduction of aldehydes to primary alcohols. For

example: propanal is reduced to propanol when reduced by hydrogen gas in the presence of a

platinum catalyst.

Before studying about the hydride reducing agents in detail, let us be familiar about different

methods of reduction, which are as follows:

3.1 Catalytic reductions: As the name suggests, it is the reduction with the help of catalysts.

Here hydrogen is added to multiple bonds in the presence of catalysts like Pt, Ni, Pd etc. The

choice of metal catalyst depends upon the compound to be used. Hydrogen gets adsorbed on

the catalyst surface and hydrogen addition takes place in the form of radical i.e., in all the

catalytic reduction: 2e- and 2H+ are added as two H. radicals. This addition is sterically

controlled and leads to syn addition. Catalytic hydrogenations are totally chemoselective and

are often chosen for this purpose over other methods of reduction.

Palladium and platinum are the most commonly used metal catalysts for hydrogenation.

CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

On the contrary, hydrogenation can also work with nickel, rhodium or ruthenium.

Substrate Usual choice of metal Benzyl amine or ether Pd

Alkene Pd, Pt or Ni

Aromatic ring Pt or Rh or Ni under high pressure

Temperature condition greatly affect the hydrogenation of various functional groups. At

lower temperatures, if two functional groups present in the same molecule, like carbonyl

and alkene double bond, only alkene is reduced and carbonyl remains unchanged.

But at higher temperatures, both alkene and carbonyl get reduced to alkane and alcohols

Important metal reduction reactions and reducing agents have been enlisted below:

Rosenmund reaction: It is a well known hydrogenation reaction in this category.

Hydrogenation of acyl chlorides yielding aldehydes is known as Rosenmund reaction.

This is good reaction for reducing compounds like carboxylic acid to their corresponding

aldehydes.

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Module 16: Reduction by Metal hydrides – Part-I

Lindlar’s catalyst: This catalyst reduces the alkynes to alkenes The Lindlar’s catalyst is

a Palladium catalyst deliberately poisoned with lead (Pd/CaCO3). The lead lessens the

activity of the catalyst and makes further reduction of the alkene product slow.

Adam’s catalyst: Adam’s catalyst is formally PtO2. This catalyst is not an oxide of

platinum, but the platinum metal that forms by reduction of PtO2 to Pt during the

hydrogenation.

Raney Nickel: This catalyst is often abbreviated as RaNi and it is a finely divide form of

nickel made from a nickel-aluminium alloy. The aluminium is dissolved away using

concentrated aqueous sodium hydroxide leaving the nickel as a fine powder.

3.2 Electroreductions and Metal reductions-In this category of reduction, the metal gives

an electron and solvent gives a proton i.e. 2e- and 2H+ are added alternately step by step as e-

, H+ , e- , H+. This is thermodynamically controlled reaction. Many metals have been used

like, Na, Mg, Zn, Sn, etc in the presence of alcohol or acid as reducing agents. Birch

reductions is one of the well-known examples of such type of reductions.

Birch reduction: The reduction of double bond systems using dissolved metal

ions like lithium, sodium in liquid ammonia is called Birch reduction. The

solvated electrons obtained from the easily ionisable Group 1 metals in ammonia

are employed as reducing agents. This reaction is regiospecific.

CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

Birch reduction works for alkynes too, and is a good way of reducing them to

trans double bonds (cis products are obtained by using Lindlar’s catalyst).

Note: Phenols and isolated double bonds are not reduced by this method.

Some examples of such reductions are drawn below:

Reduction of benzene rings

Reduction of alkynes to trans alkenes

Reduction of esters by sodium

3.3 Hydride and complex hydride reductions-In hydride reduction, the hydrogen addition

takes place as hydride ion followed by proton i.e. as H- and H+. The hydride is donated by metal

hydrides.

For example, aldehydes and ketones can be reduced by NaBH4 or LiALH4 into corresponding

alcohols.

CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

3.4 Reduction with non-metal compounds

Reductions have also been carried out by non-metal compounds such as HI, hydrogen

sulphide, ammonium sulphides, diimide, hydrazines, etc. as reducing agents.

3.5 Reduction by organic compounds

These reductions are carried by using organic compounds such as alcohols, organometallic

compounds etc. as reducing agents.

Of these different categories of reductions, we shall focus our study on Hydride reduction in this

module.

Most common Metal Hydrides: LiAlH4 and NaBH4

Sodium borohydride and lithium aluminium hydride are the most common hydride reagents.

Schlesinger and Brown and their coworkers, mentioned the synthesis and some applications of

LiAlH4 for the reduction of organic compounds, in 1947.

LiAlH4 is prepared by the reaction of lithium hydride (LiH) with aluminium chloride

(AlCl3).

CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

Sodiumborohydride is prepared by the reaction of sodium hydride (NaH) with

trimethylborate, B(OMe)3

There is difference in the reactivity of Sodium borohydride and lithium aluminium hydride.

Sodium borohydride Lithium aluminium hydride

Boron being part of second period makes

shorter and stronger bond with hydrogen

Aluminium being part of third period makes

longer and weaker bond with hydrogen.

The B-H bond of NaBH4 has more covalent

character

The Al-H bond has more ionic character in

LiAlH4

It is less reactive It is more reactive

It is a weak base It is a stronger base

Lithium aluminum hydride (LiAlH4) is known to be a powerful reducing agents for organic

compounds having polarizable functional group. They are stable at any temperature but with

moisture it get converted into hydrogen gas, lithium hydroxide and aluminum hydroxide

(hydrated alumina)

The LiAlH4 reagent is usually stable at normal temperature but in the presence of moisture, it is

destroyed as the following reaction take place.

LiAlH4 + 4 H2O LiOH + Al(OH)3 + 4 H2

Hence reactions are carried out in ethereal solvents like THF or ether.

4. Hetero atom-carbon multiple bond reduction by metal hydrides.

In general, reductions of functional groups encompass a range of reaction types and are classified

into groups depending on the type of bond undergoing reduction. These groups are carbonyl,

acids, esters and nitriles. In this module, we shall focus on the compounds having carbonyl

groups.

4.1 Reduction of carbonyl compounds

Carbonyl compounds give variety of useful derivatives. You are already familiar that they mostly

undergo nucleophilic addition reactions in which a nucleophile and a proton are added to the

carbonyl double bond. In the carbonyl group, the oxygen atom is electronegative and this results

CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

in the carbon-oxygen double bond polarization. Due to this polarized nature of the carbonyl

group, it is very reactive. The electrophilic carbon atom of the carbonyl group is sp2 hybridized

and flat, leaving it relatively unhindered and open to attack from either face of the double bond.

4.1.1 Reduction by Hydride from NaH, NaBH4 and LiAlH4

A negatively charged atom like hydride ion can act both as nucleophile and as a base. Whether a

hydride ion (H:-) will act as a nucleophile or a base depends on the reagent used.

Let us consider the H– generating from the metal hydrides NaH, NaBH4 and LiAlH4 one by one.

a. Sodium hydride (NaH):

Sodium hydride is an ionic compound. H– from NaH is very small in size and has high charge

density. It only reacts as a base and not as a nucleophile. This is because the contribution of

hydrogen atom to the σ* orbitals of the H–X bond (where X is any atom) and the filled 1s

orbital is ideal for interaction. Instead of this, 1s orbital which is filled is very small to link with

carbon’s more diffuse 2p orbital contribution to the LUMO (π*) of the C=O group.

Adding H– to the carbon atom of a C=O group would yield an alcohol and shall be a very helpful

reaction. But, the carbonyl reduction to alcohol cannot be done with NaH. So what can be added

to achieve this? The simplest answer is NaBH4 or LiAlH4.

CHEMISTRY

Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

b. Sodium borohydride (NaBH4): It is a water-soluble salt that contains tetrahedral BH4– anion,

which is isoelectronic with methane. There is a negative charge on BH4–. This is because, boron

contains one less proton in the nucleus than does carbon (analogous CH4 is neutral).

Though no hydride ion, H–, is actually involved in the reaction, the transfer of an atom of

hydrogen with an attached electrons pairs can be regarded as a ‘hydride transfer. In other

words, from BH4–, one of the H with the electron pair gets transferred. Note that it is the hydrogen

atom that forms the new bond to C. This reaction may be illustrated with a curly arrow passing

through the hydrogen atom.

The oxyanion produced in the intial step helps stabilize the electron-deficient BH3 molecule by

adding to its empty p orbital. As a result, a tetravalent boron anion is produced again, which in

turn transfers a second hydrogen atom (with its pair of electrons) to another molecule of

aldehyde.

This process can continue, in principle, so that all four atoms of hydrogen could be transferred to

molecules of aldehyde one by one. But in practice, all the four atoms of hydrogen are not

transferred. The first step is carried out in the presence of ethereal solvents like THF and diethyl

ether.

The water (or alcohol) added in subsequent step to work up provide the proton required for the

formation of the alcohol from the alkoxide ion in the last step.

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Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

Sodium borohydride reduces both aldehydes and ketones, though the reaction with ketones is

slower. For example, benzaldehyde is reduced about 400 times faster than acetophenone in iso-

propanol as solvent.

Sodium borohydride is one of the weakest hydride donors available. In fact, almost no reaction

with water is evidence of this, else it would have combined with water where H- would have

acted as base.

Specificity: Sodium borohydride is a specific reagent and does not attack of carbon-carbon

double or triple bonds of alkenes and alkynes respectively as they are not sufficiently polarised. If

multifunctional groups are there like carbonyl, alkene, and ester etc. in a molecule, it reduces

aldehyde and ketone functional groups only.

Example: In the following molecule having ketone, alkene and ester; only ketonic group is

reduced to alcoholic group. The carbon-carbon double bonds and ester functional groups are

unaffected.

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Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

There can be steric approach to control reaction. e.g., reduction of norcamphor. In this case, the

less sterically hindered exo attack is dominant, giving rise to endo-alcohol as the major product.

c. Lithium aluminium hydride (LiAlH4): In contrast to sodium borohydride, lithium aluminium

hydride is a strong hydride donor and combines rapidly with water.

Lithium aluminium hydride (LiAlH4) is more electropositive (more metallic) than boron in

NaBH4. The hydride from LiAlH4 is therefore more electron rich and thus is a stronger base (in

reaction with water) and stronger nucleophile (with carbonyl group).

Basic action: In the basic action of hydride, Lithium aluminium hydride reacts violently

and dangerously with water in an exothermic reaction that produces highly flammable

hydrogen.

Nucleophilic action: In its nucleophilic action of hydride, LiAlH4 reduces all type of

carbonyl groups viz., in aldehyde, ketones, esters, carboxylic acids and amides.

Aldehydes and ketones are reduced to primary and secondary alcohols respectively.

Mechanism of reduction by LiAlH4:

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Module 16: Reduction by Metal hydrides – Part-I

Groups not affected by LiAlH4: Other functional groups like nitro or halides are not reduced by

LiAlH4.

Other Metal Hydrides:

When the hydrogen of LiAlH4 or NaBH4 is replaced by either alkyl or alkoxy group, they lead to

the formation of variety of reducing agents.

Since LiAlH4 is a powerful reagent, it is much less chemoselective than most of the other metal

hydrides. Consequently, other metal hydrides are generally used when chemoselectivity is

desired. In order to achieve chemoselectivity, a number of less reactive (and more selective)

reagents have been prepared by replacing some of the hydrogen atoms of LiAlH4 with alkoxy

groups. This is done by treatment of LiAlH4 with ROH. Most of these hydrides of metals are

nucleophilic reagents and attack on the carbon atom of the carbon-hetero single or multiple bond.

Example: By enhancing the metal hydride into NaCNBH3, ammonia mediated reductive

introduction of amine group to aldehydes to produce primary amines was specifically achieved

without the occurrence of by product of secondary and tertiary amine.

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Paper 9: ORGANIC CHEMISTRY-III (Reaction Mechanism-2)

Module 16: Reduction by Metal hydrides – Part-I

In general, it is always better to use the mild conditions possible for any particular reaction to

reduce the potential for unwanted side reactions. Reduction with NaBH4 is a lot easier to handle

than LiAlH4—for example, it simply dissolves in water while LiAlH4 catches fire if it gets wet.

Hence, NaBH4 is usually commonly used to reduce aldehydes and ketones, even though LiAlH4

also works but proper handling is required.

5. Summary

In general, reduction can be achieved by catalytic hydrogenation, or with metals or with

metal hydrides or with organic compounds as reducing agents.

Commonly used metal hydrides are lithium aluminium hydride and sodium borohydride.

LiAlH4 is known to be a powerful and comparatively nonselective hydride-transfer

reagent. It reduces carboxylic acids, esters, lactones, anhydrides to the corresponding

alcohols and reduces amides and nitriles to the corresponding amines. Aldehydes and

ketones are readily reduced by LAH into corresponding alcohols.

Sodium borohydride reacts slowly with water and usually reactions are carried out in

ethanol at room temperature. Being less reactive than lithium aluminium hydride, it is

more selective in its action. It reduces aldehydes and ketones to the corresponding

alcohols but alkenes, alkynes, Esters, epoxides, lactones, carboxylic acids, nitro, and

nitriles are not reduced.