organomagnesium-compounds.ppt

GRIGNARD REAGENT RMgX.A Grignard reagent is an organomagnesium compound which can be described by the chemical formula 'R-Mg-X' where R refers to an alkyl or aryl group and X refers to a halogen. They are generally produced by reacting an aryl halide or an alkyl halide with magnesium.A Grignard reagent or Grignard compound is a chemical compound with the general formula R−Mg−X, where X is a halogen and R is an organic group, ..

1. Organo-magnesium Reagents
(R-Mg-X)
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

2. •The organomagnesium halides (RMgX), known as
Grignard reagents.
•(RMgX ) are useful synthetic intermediates in organic
chemistry for carbon-carbon bond formation.
•They may be regarded as polar compounds and are
sources of nuleophilic carbanions.
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

3. General
•AlthoughtheGrignardreagentsareusuallyformulated
asR-Mg-X,butinrealitytheyareamixtureofavariety
ofspecies.
•Theratioofthespeciesinsolutionvarieswiththe
organicgroup,thehalogen,thesolvent,theconcentration
andthetemperature.
•Itisbelievedthatincaseoforgano-magnesiumchlorides
(R-Mg-Cl)indiethylether,thepredominantspeciesovera
widerangeofconcentrationsisasolvated,halogen-
bridgeddimer-1(asshowninnextslide).
•Thedegreeofassociationvariesasthehalideischanged
toBrorI.
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

4. •However,incaseofTHF,duetothehighlycoordinating
natureofthesolvent,thereisalesserdegreeofassociation.
•Therefore,monomericspeciesdominateinTHF,however,
therearesignificantconcentrationsofR2Mg,MgX2and
R-Mg-Xinequilibrium.
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

5. Preparation
•TheRMgXarepreparedbytheactionofMgonalkyl,aryl
orvinylhalidesineitherdryetherorTHF,andthe
resultantsolutionisusedforthesubsequentreactions.
•Incasethereactionissluggish,smallamountofiodineis
addedtoinitiatethereaction.
•Therateoftheformationoftheorganomagnesiumhalides
canbesignificantlyacceleratedbysonication.
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

6. Reactions with Carbonyl Compounds
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

7. Mechanism
•Beingnucleophilicinnature,theR-Mg-Xundergo1,2-
additiontothecarbonylgroupofaldehydes,ketones,
esters,anhydrides,acidchloridesandamides.
•Inthesereactions,thealkyl,arylorvinylgrouphaving
carban-ioniccharacterbecomeattachedtothecarbonyl
carbonandtheMg-Xtotheoxygenofthecarbonyl
grouptogiveacomplex(additionproduct).
•Theseadditionproductsondecompositionwithproton
sourcegivethecorrespondingalcohols.
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

8. Themechanismofthisreactionisusuallydepictedtoconsist
ofthefollowingsteps-
•Complexation of the organomagnesium species with the
substrate.
•Thenextstepinvolvesnucleophilicattackoforganic
moietyofGrignardreagentontheelectrondeficient
carbonofcarbonylgroupviaamolecularcomplex.
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

9. •Theintermediateformedintheabovestepishydrolyzedto
giveatertiaryalcohol.However,ifthecarbonylgroupis
attachedwithaleavinggroup(i.e.,ifR1=OR)thenthe
tetrahedraladductcanbreakdowntoregenerateaC=O
groupthatundergoesafastsecondadditionstep.
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

10. Scheme-1
Scheme-2
Scheme-1
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

11. Anumberofmethodshavebeendevisedtostopthereactionatthe
aldehydeorketonestage.Suchprotocolsinvolvetheformationofa
maskedcarbonylcompound,whichreleasesthedesiredcompoundon
hydrolysis.
Mechanism cont….
Scheme-3
H
+
/ H
2O
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

12. Mechanism cont….
IncaseofreactionofGrignardreactionwithcarbon
dioxide,thereactionstopsatthecarboxy-late(RCO
2
-
)
stageasitisresistanttofurthernucleo-philicattack
Scheme-4
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

13. •Grignardreactionsarepronetoundergosidereactions.
•Thereactionofastericallyhinderedketonewitha
Grignardreagenthavingaβ-Hshowsatendency
towardsreductionofthecarbonylgroup.
Scheme-5
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

14. Reactions with Epoxides
•EpoxidesreactwithR-Mg-Xtoaffordaprimaryalcoholwiththe
lengtheningofthecarbonchainbytwocarbonatoms.
•However,inthiscaseofsubstitutedepoxides,theattackofthealkyl,
arylorvinylcaban-iontakesplacefromthelesssubstitutedring
carbon(stericfactor)atomoftheepoxides.
Scheme-6
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

15. Reactions with Alkyl/Alke-nyl/Aryl Halides
Alkyl,alke-nylaswellasaryltriflates,bromides,andiodidescanproceed
substitutionreactionswithR-Mg-Xinthepresenceoftransitionmetal
catalysts.Forexamples,CoCl2catalyzesthecross-couplingofPh-Mg-Br
withbenzylbromidein87%yield(Kharaschreaction).
Scheme-7
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

16. •ThecouplingofalkenylhalideswithR-Mg-Xcanbesuccessfully
carriedoutinthepresenceofNiCl
2(dppe)inhighyield.
•Inthesereactionstheexistingconfigurationofthestereo-genic
doublebondiscompletelyretained.
•Thesereactionconditionsarealsocompatibleforthecross-
couplingarylhalides/triflateswitharyl-magnesiumhalides.
Scheme-8
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

17. Scheme-9
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

18. TheC-Ccross-couplingofsecondaryR-Mg-Xmayoccurinanalogy
tothereactionoftheprimaryR-Mg-X,buttheymayalsoleadtothe
unexpectedreactionsdependingonthecatalyticsystemduetosteric
hindrancethatcouldleadtoiso-meriazationoftheC-Ccoupling.
Scheme-10
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

19. Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

20. Synthesis of Ethers
R-Mg-X with lower halogenated ethers produce higher ethers.
Scheme-11
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

21. Synthesis of Stilbene
Thesynthesisofstilbenecanbeaccomplishedbythereaction
ofbenzyl-magnesiumbromide(PhCH2MgBr)withbenzal-
dehyde,followedbydehydrationunderacidicorbasic
conditions.
Scheme-12
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

22. Synthesis of Alkyl cyanide
Thereactionofalkyl-magnesiumhalideswithcyanogensor
cyanogenschloridegivesalkylcyanides.
Scheme-13
chloride
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

23. Synthesis of Primary Amines
Thereactionofchloramineswithorganomagnesiumhalides
givesprimaryamines.
Scheme-14
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

24. Scheme-15
Synthesis of Deutrated Hydrocarbons
Deutratedhydrocarbonscanbesynthesizedbythe
reactionoforganomagnesiumhalideswithD2O
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

25. Scheme-16
Benary Reaction
Itprovidesaneffectivemethodforthesynthesisofα,β-
unsaturatedcarbonylcompoundsfrom-β(N,N-
dialkylamino)-vinylketoneandGrignardreagentby1,4-
additionfollowedbyhydrolysisandeliminationofthe
dialkylatedamine.
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

26. Bodrous Reaction
Thisreactionprovidesamethodforthepreparationofsubstitutedamides
fromaliphaticoraromaticestersandanaminomaganesiumhalidewhich
canbeobtainedfromaprimaryorsecondaryamineandGrignardreagent
atroomtemperature.
Scheme-17
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

27. Scheme-18
Bouveault Reaction
Primaryalkylhalidecanbeconvertedintoaldehydeswith
anadditionalcarbonviatheformationofGrignardreagent
followedbyreactionwithN,N-disubstitutedformamideand
hydrolysis.
Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow

28. Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow
Scheme-19
Dzhemilev Reaction
ItinvolvesthereactionofalkeneswithGrignardreagentto
givealkylmagnesiumhalideinthepresenceofCp2ZrCl2.
Thismethodhadfoundwideapplicationinorganicand
organometallicsynthesis.

29. Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow
Scheme-19
Kulinkovich Reaction
Thereactionofesterswithdi-alkyl-dialkoxy-titanium
reagents,generatedinsitufromGrignardreagentsbearing
hydrogeninβ-positionandtitanium(IV)alkoxidessuchas
titaniumisopropoxide,givescyclopropanols.

30. Dr. Mishu Singh
Pt. D. D. U Govt. Girls P.G. College, Lucknow