Lecture10

Electrophilic Addition:Purificationof Cholesterol

Reading:Experiment8oflabmanual, Zubrick,chapter13(recrystallization), Smith,chapter10section13(halogenation ofalkenes)

ChemistryandBiochemistryofCholesterol
H3C CH3 CH3 HO CH3 CH3

HO

rigidifiescellmembranes 200gperadult(brain/nervetissue) biosyntheticprecursorto: bileacids vitaminD estrogen testosterone

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ImpuritiesinCholesterol
H3C CH3 CH3 HO CH3 CH3

cholesterol H3C CH3 CH3 CH3 HO CH3 CH3

H3C CH3 CH3 HO H3C CH3 CH3 HO CH3 CH3

CH3

H3C CH3 CH3 HO

OH CH3 CH3

Addition Reactions
The characteristic reaction of alkenes is additionthe addition the bond is broken and two new bonds are formed.

Because alkenes lk are electron l rich, h they h react with h electrophiles. l hl

Halogenation Electrophilic Addition ofHalogen

Halogenation is the addition of X2 (X = Cl or Br) to an alkene to form a vicinal dihalide dihalide.

Sometimesusedasproofoftheexistenceofa C=Cgroup(seeDehydrationofCyclohexanol)

Halogenation Details
Halogensaddto bondsbecausehalogensarepolarizable. Theelectronrichdoublebondinducesadipoleinanapproachinghalogen molecule,makingonehalogenatomelectrondeficientandtheotherelectron rich(X+X). Theelectrophilic halogenatomisthenattractedtothenucleophilic double bond,makingadditionpossible. Twofactsdemonstratethathalogenation followsadifferentmechanismfrom thatofhydrohalogenation orhydration. Norearrangementsoccur. OnlyantiadditionofX2 isobserved. Thesefactssuggestthatcarbocations arenotintermediates.
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Halogenation Mechanism

StereochemistryofHalonium Formation
C Consider id the th chlorination hl i ti of fcyclopentene l t t afford to ff db both thenantiomers ti of ftrans t 1,2dichlorocyclopentane,withnocis products. Initialadditionoftheelectrophile Cl+ from(Cl2)occursfromeithersideofthe planar l double d bl b bond dt tof formab bridged id dchloronium hl i i ion.

StereochemistryofHalonium RingOpening
Inthesecondstep,nucleophilic attackofClmustoccurfromthebackside. Sincethenucleophile attacksfrombelowandtheleavinggroupdepartsfrom above,thetwoCl atomsintheproductareorientedtranstoeachother. Backsideattackoccurswithequalprobabilityateithercarbonofthethree membered ringtoyieldaracemic mixture.

Reactionsthisweek:

Questions: Whydoesthishelppurifycholesterol? Whatisthestereochemistryofthesereactions? Howdoweknowthis?

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TheHalogenation Mechanism

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Dehalogenation withZnmetal

Axialleavinggroupsarebest..why?

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Methodsofpurification: recrystallization extraction(washingwithsodiumhydroxide) dryingtoremovewater Methodsofdemonstratingpurity: colorandtextureofcrystals meltingpoint Methodsofdemonstratingidentity meltingpoint(comparedtoliterature) Alsopossible, Al ibl but b wewont have h time: i infraredspectroscopy(actually,dothisifyouwantto!) nuclearmagneticresonancespectroscopy massspectrometry
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IRSpectrumofCholesterol

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