2. LiAlH4

Characteristics and uses of LiAlH4 is discussed

1. 2. LiAlH
4
Dr. ShivendraSingh
UGC-NET-JRF, PhD-IIT Indore

2. …Lithium aluminium hydride
LiAlH
4isareducingagent.Morespecifically,nucleophilicreducing
agentandusedtoreducepolarmultiplebondslikeC=O.
ThereisatetrahedralarrangementofhydrogensaroundAl
3+
in
aluminiumhydride,AlH
4-
ion.
ThehybridizationincentralAlissp
3
.
LiAlH
4

3. …Lithium aluminium hydride: Preparation
LAHispreparedbythereactionbetweenlithiumhydrideand
aluminiumchloride.
LiAlH
4

4. …Lithium aluminium hydride: Properties
1.LAHisawhitesolidbutthecommercialsamplesareusuallygray
(duetopresenceofimpurities).
2.Itreactsviolentlywithwaterbyproducinghydrogengasand
thereforeitshouldnotbeexposedtomoistureandthereactionsare
performedininertanddryatmosphere.(anhydrousnon-protic
solvents)
LiAlH
4

5. …Lithium aluminium hydride: Properties
3.Asfarasthepreferenceofsolventisconcerned,itishighlysolublein
diethylether.Howeveritmayspontaneouslydecomposeinitdueto
presenceofcatalyticimpurities.ThereforethepreferredsolventforLAH
isTHFdespitethelowsolubility.
LiAlH
4

6. …Lithium aluminium hydride: Properties
Workup:
Duringtheworkup,thereactionmixtureisinitiallychilledinanicebath
andthentheLithiumaluminiumhydrideisquenchedbycarefulandvery
slowadditionofethylacetatefollowedbytheadditionofmethanoland
thencoldwater.
LiAlH
4

7. …LAH: Mechanism of reduction
ThereductionofacarbonylgroupbyLiAlH
4isinitiatedbytheattackof
nucleophilichydrideiononthecarbonylcarbontogiveatetrahedral
intermediate.
LiAlH
4isanucleophilicreducingagentsincethehydridetransfertothe
carbonylcarbonoccurspriortothecoordinationtothecarbonyloxygen.
Itreactsfasterwithelectrondeficientcarbonylgroups.Thereactivityof
carbonylcompoundswiththisreagentfollowstheorder:
Aldehydes > Ketones > Ester > Amide > Carboxylic acid
LiAlH
4

8. …LAH: Mechanism of reduction
i.MechanismofReductionofcarbonylstoalcohols:Ahydrideionis
transferredontothecarbonylcarbonandtheoxygenatomcoordinatesto
theremainingaluminiumhydridespeciestofurnish(I),whichcanreduce2
morecarbonylmolecules.
LiAlH
4
(three of the hydride
ions are used up)
Alkoxytrihydroaluminate ion (I)

9. …LAH: Mechanism of reduction
ii.Mechanism of Reduction of Esters to 1
°
alcohols:The ester is first
converted to aldehyde which is further reduced to primary alcohol.
LiAlH
4

10. …LAH: Mechanism of reduction
iii.MechanismofReductionofAmidestoamines:TheLAHreduction
mechanismisslightlydifferenthere.Iminiumionisformedduringthe
reactionsincenitrogenatomisrelativelyagooddonorthanoxygen
atom.
LiAlH
4

11. iv.MechanismofReductionofnitrilestoprimaryamines:Initially,the
polarCNbondisaddedwithLAHsuchthatthenegativelycharged
hydridemakesbondwithcarbon;followedbysubsequenttransferof
hydridefromAlH
3-
group.Finalproteicworkupgeneratesamine
group.
…LAH: Mechanism of reduction
LiAlH
4

12. …Lithium aluminium hydride: Applications
LiAlH
4
Substrate Product
Aldehyde Primary alcohol
Ketone Secondary alcohol
Carboxylic acids Primary alcohol
Esters Primary alcohol
Amides Amines
Nitriles Amines
Epoxides Alcohols
Lactones Diols

13. …Lithium aluminium hydride: Applications
Lithiumaluminiumhydride,LAHreagentcannotreduceanisolatednon-
polarmultiplebondlikeC=C.However,thedoubleortriplebondsin
conjugationwiththepolarmultiplebondscanbereduced.
LiAlH
4

14. …LAH: Applications
1) Reduction of carbonyl compounds using LiAlH
4:
LiAlH
4

15. …LAH: Applications
…Reduction of carbonyl compounds using LiAlH
4:
LiAlH
4

16. …LAH: Applications
Stereochemistry:Theaxialattackofhydrideionispreferredoverthe
equatorialattackincaseofcyclicsystems.Forexample,4-t-
butylcyclohexanoneyieldsmorethan90%oftrans-4-t-butylcyclohexanol
whenreducedwithLAH.
LiAlH
4

17. …LAH: Applications
Theplausibleexplanationforthisbehavioris:the-OHgroupprefersthe
equatorialpositiontoavoidtheinteractionswithotheraxialhydrogens.
i.e.,Itisnottheapproachofhydrideionbuttheorientationof-OHgroup
whichdecidesthefinalstereochemistry.
LiAlH
4

18. …LAH: Applications
2)Thecarboxylicacids,acidhalidesandestersarereducedto
correspondingprimaryalcohols.
LiAlH
4

19. …LAH: Applications
3) The amides are reduced to amines.
4) The nitriles are reduced to primary amines.
LiAlH
4

20. …LAH: Applications
5) LAH reduces the oxiranes (epoxides) to alcohols. The mechanism
involves hydride attack at less hindered sideof the epoxide.
LiAlH
4

21. …LAH: Applications
6) The lactonesare reduced to α,ω-diols by LiAlH
4.
7)Thehaloalkanesandhaloarenesarereducedtocorresponding
hydrocarbons.
LiAlH
4

22. …LAH: Applications
MODERN METHODS OF ORGANIC SYNTHESIS, W. CARRUTHERS , IAIN COLDHAM

23. …LAH: SUMMARY
1.Structure
2.Preparation
3.Properties (3)
4.Mechanism
(Carbonyls, esters,
amides, nitriles)
5.Application (7)
i.Carbonyls
ii.Carboxylic acids
iii.Amides
iv.Nitriles
v.Epoxides
vi.Lactones
vii.Haloalkanes & haloarenes

24. Next: NaBH
4
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