Lithium aluminium hydride (LiAlH4 or LAH) * Lithium aluminium hydride, LiAlH4, also abbreviated as LAH, is a reducing agent commonly employed in modern organic synthesis.

* It is a nucleophilic reducing agent, best used to reduce polar multiple bonds like C=O.

* LiAlH4 can reduce aldehydes to primary alcohols, ketones to secondary alcohols, carboxylic acids and esters to primary alcohols, amides and nitriles to amines, epoxides to alcohols and lactones to diols.

* Lithium aluminium hydride cannot reduce an isolated non-polar multiple bond like C=C. However, the double or triple bonds in conjugation with the polar multiple bonds can be reduced.

* LiAlH4 is a powerful reducing agent than sodium borohydride, NaBH4 since the Al-H bond is weaker than B-H bond.

Structure of Lithium aluminium hydride - LiAlH4

There is a tetrahedral arrangement of hydrogens around aluminium in aluminium hydride, AlH4- ion. 

Preparation of LiAlH4

LiAlH4 is prepared by the reaction between lithium hydride and aluminium chloride.

Properties of LiAlH4 , Reaction conditions & Workup

* Lithium aluminium hydride is a white solid but the commercial samples are usually gray due to presence of impurities.

* It reacts violently with water by producing hydrogen gas. Hence it should not be exposed to moisture and the reactions are performed in inert and dry atmosphere. 

* The reaction must be carried out in anhydrous non protic solvents like diethyl ether, THF etc. It is highly soluble in diethyl ether. However it may spontaneously decompose in it due to presence of catalytic impurities. Therefore the  preferred solvent for LAH is THF despite the low solubility.

* The reactions are usually performed with excess of LiAlH4. A small amount of the reagent is added to the solvent to eliminate any moisture present in the solvent.

Workup:

During the workup, the reaction mixture is initially chilled in an ice bath and then the Lithium aluminium hydride is quenched by careful and very slow addition of ethyl acetate followed by the addition of methanol and then cold water.

Sometimes, the reagent is decomposed by adding undried solvent slowly and then dilute sulphuric acid to the reaction mixture.

 

MECHANISM OF REDUCTION BY LITHIUM ALUMINIUM HYDRIDE

* The reduction of a carbonyl group by LiAlH4 is initiated by the attack of nucleophilic hydride ion on the carbonyl carbon to give a tetrahedral intermediate.

* LiAlH4 is a nucleophilic reducing agent since the hydride transfer to the carbonyl carbon occurs prior to the coordination to the carbonyl oxygen. It reacts faster with electron deficient carbonyl groups. The reactivity of carbonyl compounds with this reagent follows the order:

Aldehydes > Ketones > ester > amide > carboxylic acid

* The steps involved in the reduction of various functional groups are shown below:

Reduction of Aldehydes or Ketones to 10 or 20 alcohols: Initially, a hydride ion is transferred onto the carbonyl carbon and the oxygen atom coordinates to the remaining aluminium hydride species to furnish an alkoxytrihydroaluminate ion, which can reduce the next carbonyl molecule. Thus three of the hydride ions are used up in reduction.

Reduction of Esters to 10 alcohols: The ester is first converted to aldehyde which is further reduced to primary alcohol.

Reduction of Amides to amines: Amides are converted to amines. The mechanism is slightly different from that depicted for esters. In iminium ion is formed during the reaction since nitrogen atom is relatively a good donor than oxygen atom. 

Reduction of nitriles to primary amines: 

 

APPLICATIONS OF LiAlH4

 The summary chart of applications of LiAlH4 in the reduction of different types of functional groups.

 Functional group conversion   equivalents of

LiAlH4 

  Aldehydes, ketones ------->   Alcohols   1

  Carboxylic acids     -------> Alcohols   3

  Esters, acid halides -------> Alcohols   2

  Amides -------> amines   2

  Nitriles   ------->   amines   2

  oxiranes (epoxides) ------->   alcohols 1

  lactones ------->   diols 2

 haloalkanes, haloarenes ------->   alkanes, arenes 1

 

1) The aldehydes or ketones are reduced by LiAlH4 to the corresponding primary or secondary alcohols respectively. 

E.g. Acetaldehyde is reduced to ethyl alcohol and acetone is reduced to isopropyl alcohol.

* LiAlH4 does not affect the isolated carbon-carbon double or triple bonds.

*However, the double bonds in conjugation at α,β positions of carbonyl group may also be reduced by Lithium aluminium hydride depending on the reaction conditions.

E.g. Cinnamaldehyde is reduced to Hydrocinnamyl alcohol when reduced with excess of LiAlH4 (roughly more than 2 equivalents) by normal addition method. In this method, a solution of cinnamaldehyde is added to the solution of lithium aluminium hydride. Both the double bond and carbonyl group are reduced.

Whereas, Cinnamaldehyde is reduced to Cinnamyl alcohol with one equivalent of LiAlH4 in inverse addition method. In this method, the solution of LiAlH4 is added to the solution of Cinnamaldehyde. Only the carbonly group is reduced to alcohol.

Stereochemistry:

The axial attack of hydride ion is preferred over the equatorial attack in case of cyclic systems. For example, 4-t-butylcyclohexanone yields more than 90% of trans-4-t-butylcyclohexanol when reduced with Lithium aluminium hydride.

The plausible explanation for this behavior is: the -OH group prefers the equatorial position to avoid the interactions with other axial hydrogens. i.e., It is not the approach of hydride ion but the orientation of -OH group which decides the final stereochemistry.

2) The carboxylic acids, esters and acid halides are reduced to corresponding primary alcohols by Lithium aluminium hydride.

E.g. The reduction of Acetic acid, methyl acetate and acetyl chloride by LiAlH4 furnish the same ethyl alcohol.

 

3) The amides are reduced to amines by LAH. Especially this method is used to get secondary amines.

E.g. Diethyl amine can be prepared starting from acetyl chloride as follows:

4) The nitriles are reduced to primary amines by LiAlH4. 

E.g. Acetonitrile is reduced to ethyl amine by LiAlH4.

5) Lithium aluminium hydride reduces the oxiranes (epoxides) to alcohols. The hydride attack occurs at less hindered side of the epoxide.

E.g. 2-methyloxirane gives 2-propanol predominantly.

In case of cyclohexene epoxides, the axial alcohols are formed preferentially. 

E.g.

6) The lactones are reduced to α,ω-diols by Lithium aluminium hydride.

E.g.

7) The haloalkanes and haloarenes are reduced to corresponding hydrocarbons by LiAlH4.

FETIZON'S REAGENT (Ag2CO3/Celite) Silver carbonate, Ag2CO3 precipitated on Celite is called Fetizon's reagent. It is used to oxidize primary and secondary alcohols to aldehydes and ketones respectively under mild and neutral conditions on small scale. The Ag+ ion is reduced to metallic Ag0.

PREPARATION OF FETIZON'S REAGENT

The Fetizon's reagent is prepared as follows:

i) Initially Celite is purified by washing with methanol containing HCl and then with distilled water.

Note: Celite is the diatomaceous or siliceous earth mainly composed of silica.

ii) Purified Celite is added to silver nitrate solution in distilled water and then a solution of sodium carbonate is added to it slowly with stirring. The yellow green precipitate obtained is filtered off and dried. 

The precipitate containing silver carbonate over celite is used as Fetizon's reagent. It has enhanced reactivity and can be filtered easily.

REACTION CONDITIONS & WORKUP

The reaction with Fetizon's reagent is carried out just by refluxing the reaction mixture in neutral apolar solvents such as benzene or heptane and the product is recovered in high purity by simply filtering off the Ag0 formed and evaporating the solvent.

The use of polar solvents with weak basic nature like ethyl acetate, diethyl ether etc., must be avoided since they may inhibit the oxidation by complexing to the silver ions and prevent the initial chemisorption of alcohol over surface of the reagent.

The water produced during the oxidation must be removed by performing azeotropic distillation using Dean-Stark apparatus. Otherwise it may inhibit the action of Fetizon's reagent by competing with the alcohol for complexing with silver ions.

Usually excess of the reagent is employed during the oxidation reaction.

 

REACTION MECHANISM

The oxidation with Fetizon's reagent is believed to occur through chemisorption of alcohol over the surface of silver carbonate. The oxygen atom of the -OH group and the α-hydrogen atom complex to the Ag+ ions, which are subsequently reduced to Ag0. 

 

The overall reaction can be represented as:

APPLICATIONS OF FETIZON'S REAGENT

The Fetizon's reagent is used to oxidize alcoholic groups selectively in presence of non-polar functional groups. However the polar functional groups, may retard the rate of the reaction though not affected by the reagent. This is because of their complexing ability with the silver ions.

* The ease of oxidation of alcohols by Fetizon's reagent  follows the trend: allylic, benzylic alcohols > 2' alcohols> 1' alcohols.

* However highly hindered -OH groups are not oxidized.

* The treatment of diols with Fetizon's reagent usually promotes oxidation of only one of the -OH group. 

* The α,ω-diols (like1,4; 1,5; 1,6) containing two primary alcoholic groups give corresponding lactones via lactols. Initially, one of the hydroxyl group is oxidized to aldehyde, which cyclizes to an intermediate lactol. Further oxidation of lactol furnishes lactone.

ILLUSTRATIONS

1) The secondary hydroxyl groups react faster than the primary hydroxyl groups with Fetizon's reagent. Hence it is used to selectively oxidize secondary alcoholic groups as illustrated below.

2) The allylic alcoholic groups are selectively oxidized in presence of primary and secondary alcohols.

3) The treatment of 1,5-pentanediol with Fetizon's reagent furnishes a δ-lactone. Initially one of the -OH group is oxidized to yield a hydroxyaldehyde that equilibrates with a small amount of hemiacetal, which is further oxidized to an δ-lactone.

GRIGNARD REAGENT & REACTIONS * The organomagnesium halides are known as Grignard reagents. These are extremely important reagents developed by the French chemist François Auguste Victor Grignard, who was awarded the Nobel Prize in 1912 in Chemistry for this work.

The Grignard reagent is represented as R-Mg-X, where

    R = alkyl / aryl / alkenyl / allyl group

    X = Cl / Br / I

* The reactions involving Grignard reagents, as sources of nucleophiles, are usually referred to as Grignard reactions.

 

PREPARATION OF GRIGNARD REAGENT 

* The Grignard reagents are prepared by the action of activated magnesium (Rieke magnesium) on organic halides in suitable solvents like Diethyl ether, Et2O or Tetrahydrofuran, THF in anhydrous conditions. 

* This is an oxidative insertion of magnesium between carbon and halogen bond, which involves oxidation of Mg(0) to Mg(II). The mechanism of this reaction if not quiet conclusive.

* The Grignard reagents are in equilibrium with the dialkylmagnesium species R2Mg and MgX2 (Schlenk equilibrium).

* In the formation of Grignard reagent, the polarity of carbon attached to the halide group is reversed. This reversal in polarity is called as umpolung.

REACTION CONDITIONS

Activation of magnesium metal:

* Magnesium metal is usually unreactive due to formation of oxide layer on its surface. Hence it should be activated by dislodging this layer. It is achieved by adding small amount of iodine or 1,2-dioiodoethane or by using ultrasonic sound. 

This problem can also be obviated  by using Rieke magnesium, which is in the form of highly reactive small particles of magnesium with large surface area. It is prepared by reducing MgCl2 with lithium metal. 

Solvent:

* Ether solvents like Diethyl ether, Et2O or Tetrahydrofuran, THF or Dimethoxyethane, DME or Dioxane are most suitable for the preparation of Grignard reagents. It is because they are not only unreactive with magnesium but also dissolve and stabilize the Grignard reagents by forming Lewi's acid base complexes.

* The major disadvantage of Grignard reagents is they react with protic compounds like water, alcohols, thiols etc. Hence the reaction must be carried out under anhydrous conditions avoiding moisture.

* These reagents must not be exposed to air as they also react with oxygen by giving peroxide species which are converted to corresponding alcohols during hydrolytic workup. To avoid this, it may be preferable to carry out the reaction in nitrogen or argon atmosphere.

PREPARATION OF DIFFERENT TYPES OF GRIGNARD REAGENTS 

* The alkyl Grignard reagents are prepared from the corresponding chlorides or bromides or iodides. The order of reactivity of alkyl halides with magnesium is  RCl < RBr < RI. Alkyl fluorides are seldom used due to much less reactivity.

* The alkenyl and phenyl Grignard reagents are prepared from the corresponding bromides or iodides in more effective co-ordinating solvent like THF. 

E.g. Vinyl bromide and bromobenzene can be converted to corresponding Grignard reagents by reacting them with magnesium metal in anhydrous THF.

* The alkynyl Grignard reagents are prepared by deprotonating 1-alkynes with another Grignard reagent like Ethylmagnesium bromide.

E.g. Propyne can be deprotonated with ethylmagnesium bromide to give propynylmagnesium bromide.

* The allylic Grignard reagents  may undergo coupling reactions. Hence they are generated in situ whenever required in the Grignard reactions.

* Grignard reagents can also be prepared by transmetallation. 

E.g. Alkyllithiums can give Grignard reagents when treated with magnesium salts.

 

 

REACTIONS OF GRIGNARD REAGENTS

* The Grignard reagents are highly basic and can react with protic compounds like water, acids, alcohols, 1-alkynes etc., by giving corresponding alkanes.

E.g. Ethylmagnesium bromide liberates ethane gas when treated with water.

The reaction of Grignard reagent with D2O can be used to introduce a deuterium atom selectively at a particular carbon atom.

* However the Grignard reagents are less basic than organolithiums and hence are more suitable nucleophiles for carbon-carbon bond formation.

* The Grignard reagents are used as sources of carbon nucleophiles (carbanions) and can react with electrophilic centers. The addition reactions involving Grignard reagents with compounds containing polarized multiple bonds like aldehydes, ketones, esters, acid halides, nitriles, carbon dioxide etc., are termed as Grignard reactions.

* The reactivity of carbonyl compounds with Grignard reagents follow the order: aldehydes > ketones > esters > amides

MECHANISM OF GRIGNARD REACTION

* The first step in the Grignard reaction is the nucleophilic addition of Grignard reagent to the polar multiple bond to give an adduct which upon hydrolytic workup gives the final product like alcohol. 

E.g. The mechanism of reaction with a carbonyl compound is shown below.

 

APPLICATIONS OF GRIGNARD REAGENT

 Following is the summary chart of applications of Grignard reagent in modern organic synthesis.

Grignard reaction    Product

R-Mg-X + 

 Formaldehyde (   HCHO ) ------->  A primary alcohol:   R-CH 2-OH   Aldehyde (R'-CHO) ------->  A secondary alcohol: R'-CH(OH)-R  Ketone (R'-CO-R") ------->  A tertiary alcohol: R'-CR"(OH)-R  Ester (R'-COOR") ------->  A tertiary alcohol: R'-CR(OH)-R  Acid halide (R'-COX) ------->   A tertiary alcohol: R'-CR(OH)-R  CO2 ------->  A carboxylic acid: R-COOH  CS2 ------->  A dithionic acid: R-CSSH  SO2 ------->  A sulphinic acid: R-SOOH   SO 3 ------->  A sulphonic acid: R-SO2OH   nitriles (R'-CN) ------->  A ketone: RCOR'  Hydrogen Cyanide (HCN) ------->  An aldehyde: RCHO  Oxiranes (epoxides) ------->  Alcohols  Weinreb amide ------->  A ketone  cyanogen ------->  A nitrile  choramine ------->  An amine  Iodine ------->  Alkyl iodide  Sulfur ------->   A thiol  halides of B, Si, P, Sn ------->  compounds with C- hetero atom bonds  CdCl2 ------->  Dialkyl cadmium

 

1) The addition of Grignard reagents to formaldehyde furnishes primary alcohols.

E.g.  The addition of  Ethylmagnesium iodide to formaldehyde followed by hydrolytic workup furnishes Propyl alcohol, a primary alcohol.

 

2) The Grignard reaction with aldehydes other than formaldehyde gives secondary alcohols.

E.g. The addition of Methylmagnesium iodide to acetaldehyde gives Isopropyl alcohol.

 

3) The addition of Grignard reagent to ketones furnishes tertiary alcohols.

E.g. The addition of Methylmagnesium iodide to acetone gives tert-Butyl alcohol.

Stereochemistry:

The carbonyl carbon of an unsymmetrical ketone is a prochiral center. Therefore the addition of a Grignard reagent  can take place on either face of the carbonyl group with equal chance. Hence a racemic mixture is formed in absence of asymmetric induction.

E.g.

However a mixture of diastereomers is formed when the ketone or aldehyde contains at least one chiral center. The predominant stereoisomer formed in this case can be predicted by using Cram's rule. 

E.g. The reaction of (R)-2-phenylpropanal with ethylmagnesium bromide, an achiral Grignard reagent furnishes the (R,R)-2-phenyl-3-pentanol as major product.

Side reactions:

However, the abstraction of an α-hydrogen by Grignard reagent (in this case it acts as a base) is observed with sterically hindered ketones to furnish an enolate intermediate. The protic workup of the enolate ends up in the recovery of the starting ketone.

 

If the Grignard reagent contains a β-hydrogen, reduction of carbonyl compound by hydride transfer may compete with the desired addition reaction (see below). Hence the Grignard reagent with smallest possible alkyl group is to be used to avoid this side reaction. Also the use of corresponding organolithium compounds is advisable to suppress the enolization products.

 

It is also observed that the tertiary magnesium alkoxides bearing a β-hydrogen, may undergo a dehydration reaction during protic workup, and thus by giving an elimination product, alkene instead of alcohol.

E.g.

 

4) The esters are less reactive than aldehydes and ketones. However they give tertiary alcohols with excess (2 moles) of Grignard reagent. The initial addition product formed will decompose to a ketone which reacts with the second Grignard reagent to furnish the tertiary alcohol finally.

E.g. Ethyl acetate reacts with two moles of phenylmagnesium iodide and thus by furnishing 1,1-diphenylethanol, a tertiary alcohol. 

 

5) The acid halides also react with 2 moles of Grignard reagent to furnish tertiary alcohols. Again the reaction proceeds through the intermediate ketone.

E.g. Acetyl chloride reacts with two moles of Ethylmagnesium bromide to furnish 3-methylpentan-3-ol.

However, it is also possible to get the ketone in higher yields by using one mole of Grignard reagent.

 

6) The Grignard reagents react with carbon dioxide to give carboxylic acids.

E.g. Methylmagnesium chloride gives acetic acid when reacted with carbon dioixide.

    An analogous reaction of Grignard reagent is observed with carbon disulphide, CS2, to give alkanedithionic acid.

E.g. Ethanedithionic acid can be prepared by reacting methylmagnesium chloride with carbon disulphide, CS2.

 

    Also in another analogous reaction with sulfur dioxide, SO2, an alkanesulphinic acid is formed.

E.g. Methanesulphinic acid is formed when methylmagnesium chloride reacts with sulfur dioxide, SO2.

    Whereas, alkane sulphonic acids are formed with sulfur trioxide, SO3.

7) The nitriles furnishes ketones with Grignard reagents.

E.g. Acetonitrile gives acetone when reacted with methyl magnesium iodide.

    However, aldehydes are obtained with hydrogen cyanide, HCN.

 

8) The oxiranes (epoxides) furnish alcohols with Grignard reagents.

E.g. Secondary butyl alcohol is obtained when 2-methyloxirane reacts with methylmagnesium iodide. 

The less substituted carbon of oxirane is substituted by the alkyl group of Grignard reagent.

 

9) Addition of an N-methoxy-N-methyl amide, also known as Weinreb amide, RCON(Me)OMe, to the Grignard reagent gives a ketone. Initially the Grignard reagent is added to the Weinreb amide, which further undergoes hydrolysis to furnish ketone.

E.g. The addition of n-butylmagnesium bromide to the following Weinreb amide furnishes 3-heptanone.

10) The Grignard reagents are also used to prepare nitriles by reacting them with cyanogen or cyanogen chloride.

11) Amines can be prepared by reacting these reagents with Chloramine, NH2Cl.

12) The alkyl iodides can be prepared via Grignard reagents. The alkylmagnesium chlorides or bromides are treated with Iodine to get corresponding alkyl iodides.

13) A Wurtz like coupling reaction is also possible when the Grignard reagent is treated with an alkyl halide to furnish an alkane. Indeed it is a side reaction that may be possible during the preparation of Grignard reagent. This reaction is catalyzed by Cuprous (CuI) ions.

14) Just like oxygen, the sulfur atom is also inserted into the Grignard reagent, which gives a thiol upon protic workup.

15) The Grignard reagent is also used in the making of bond between a carbon and other hetero atom like B, Si, P, Sn etc. These applications are depicted in the following reactions.

16) Dialkyl cadmium compounds are formed when the Grignard reagents are made to react with cadmium chloride.

The dialkyl cadmium compounds furnish ketones upon reacting with acid halides.

Diisobutylaluminium hydride (DIBAL or DIBAL-H or DIBAH) * Diisobutylaluminium hydride, iBu2AlH  also known as DIBAL or DIBAL-H or DIBAH is an exceedingly useful and versatile reducing agent. 

* It is an electrophilic reducing agent, usually employed in selective reductions of esters or nitriles to aldehydes;  lactones to lactols;  α,β-unsaturated carbonyl compounds to allylic alcohols, at low temperatures (-78oC).

* DIBAL-H reduces carbonyl or nitrile groups selectively in presence of double bonds, halide groups, ethers, nitro groups etc.,

 

Structure of DIBAL

DIBAL is an organoaluminium hydride existing as a dimer, (iBu2AlH)2 or as a trimer, (iBu2AlH)3.

Preparation of DIBAL

DIBAH can be prepared by heating Triisobutylaluminium, TIBAL. It is a β-hydride elimination reaction.

 

Properties of DIBAL reagent, Reaction conditions & Workup

* Commercially, DIBAL can be obtained as a neat colorless liquid or as a solution in hydrocarbon solvents like toluene.

* It is miscible with numerous solvents. Diethyl ether, THF, methylene chloride, chlorobenzene, toluene,hexane etc., are the suitable solvents.

* But it undergoes rapid oxidation in air and reacts vigorously with hydroxylic compounds such as water, alcohol etc. Hence the reductions with DIBAL should be carried out in the absence of air and moisture.

* The workup involves slow quenching with methanol followed by complete quenching with water. Alternatively, dil.HCl can be employed. Methanol destroys excess of DIBAL-H.

 

MECHANISM OF DIBAL

* DIBAL is said to be an electrophilic reducing agent because of its coordination to the carbonyl oxygen prior to the transfer of hydride onto carbonyl carbon. Hence it reacts fast with electron rich carbonyl groups.

Note: In contrast, LiAlH4 is a nucleophilic reducing agent since the hydride transfer occurs prior to the coordination to the carbonyl oxygen. It reacts fast with electron deficient carbonyl groups.

* At low temperatures (-78oC),  the reduction of esters, nitriles and lactones can be stopped after the transfer of one hydride to the carbonyl carbon. It is because the tetrahedral intermediate formed is stable at low temperatures. This tetrahedral intermediate will furnish the corresponding aldehyde only upon hydrolytic workup.

* But at higher temperatures, the carbonyl compound takes one more hydride and thus by forming alcohols finally. Hence DIBAL can also be used to reduce carbonyl compounds to alcohols.

 

APPLICATIONS OF DIBAL

 Following is the summary chart of application of DIBAL-H in the conversion of different types of functional groups.

 Functional group conversion   Reaction conditions 

equivalents of DIBAL-H  Temperature

  Aldehydes, ketones ------->   Alcohols    1  higher

  Carboxylic acids     -------> Alcohols    3   higher

  Esters -------> Alcohols    3 to 4   higher

  Carboxylic acids     -------> Aldehydes    2   lower

  Esters -------> Aldehydes    1  lower

  Lactones -------> Lactols    1  lower

  α,β-unsaturated esters   ------->   Allylic alcohols    2  lower

  Nitriles ------->   Aldehydes 1 lower

  Nitriles ------->   Amines 2 lower

 

1) Aldehydes, Ketones, Carboxylic acids & Esters to Alcohols: At ordinary temperatures, DIBAL-H reduces variety of carbonyl compounds, like aldehydes, ketones, carboxylic acids and esters, to corresponding alcohols.  These reductions are chemoselective as well as stereospecific.

One or less than one equivalent of DIBAL-H is required for the reductions of aldehydes or ketones.

E.g. i) Cinnamaldehyde can be reduced to cinnamyl alcohol. It is observed that only one-third of an equivalent of  DIBAL-H is required  and isobutylene is formed as a byproduct. This indicates, not only the hydrogen on

aluminium but also the β-hydrogen on isobutyl groups participates in the reduction. But the double bond is intact during the reduction. A case of chemoselectivity.

Thus DIBAL-H is the reagent of choice for the reduction of α,β-unsaturated carbonyl compounds to allylic alcohols.

 

E.g. ii) Isoborneol is formed as major product when camphor is reduced with DIBAL-H. It is a stereospecific reaction. The hydride attack occurs from the less hindered side of the carbonyl group.

 

Carboxylic acids require 3 moles of DIBAL-H for their conversion into alcohols at higher temperatures. One equivalent is consumed for the formation of salt of carboxylic acid. The rest for the conversion into alcohol.

E.g. iii) Benzoic acid requires 3 equivalents of DIBAL-H for its conversion into benzyl alcohol.

But in case of esters, 3 to 4 equivalents of DIBAL-H are required at ordinary temperatures. It may be due to formation of two alkoxyalumino intermediates, which then give corresponding alcohols.

 

2) Carboxylic acids or Esters to Aldehydes: However, at lower temperatures (around -78oC), carboxylic acids (with 2 equiv. of DIBAL-H) or esters (with 1 equiv. of DIBAL-H) are selectively reduced to aldehydes (see the explanation above in mechanism section).

E.g. i) Benzoic acid is reduced to benzaldehyde with two equivalents of DIBAL-H at -70oC.

E.g. ii) Ethyl phenylacetate is reduced to phenyl acetaldehyde with only one equivalent of DIBAL-H at -70oC.

 

3) Lactones (cyclic esters) are reduced to lactols (cyclic hemiacetals) with DIBAL-H at low temperatures.

 

4) α,β-unsaturated carbonyl compounds are reduced to allylic alcohols with DIBAL-H. 

E.g. Following α,β-unsaturated ester is converted to allylic alcohol with 2 equivalents of DIBAL-H at low temperatures (is not converted to aldehyde!?).

 

5) Nitriles to aldehydes or primary amines: The nitriles are either reduced to aldehydes or primary amines depending on the amount of DIBAL-H consumed. 

Nitriles are reduced to aldehydes when treated with one equivalent of DIBAL-H at low temperature (-780C) followed by hydrolytic workup.

But they produce primary amines upon treatment with two equivalents of DIBAL-H, usually at room temperature, followed by protic workup.

E.g. i) In the following reduction, the double bond is intact while the nitrile is converted to aldehyde.

 

 

E.g. ii) 3,4-Dicyanofuran can be reduced to corresponding dialdehyde with two equivalents of DIBAL-H.

 

E.g. iii) Benzonitrile is reduced to Benzylamine when 2 equivalents of DIBAL-H are used at 110oC.

 

6) DIBAL-H can also be used in reduction of: alkynes to cis-alkenes; terminal olefins  to alkanes.