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D R . E D D Y  

CHEM 2445 - Aldol

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The Experiment

 Aldol condensation of benzaldehyde and acetone

Chapter 3! p" 4#4

Macroscale proced$re p" 4#%

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 Aldol Condensation

&eaction bet'een 2 carbonyls $nder basic conditions

(asic conditions )enerate enolate  Acti*e n$cleophile

+ntermediate aldol prod$ct can be dehydrated $nderthermodynamic conditions

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Mechanism

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,eneral eat$res

Catalytic 'ith hydroxide

E.$ilibri$m established p/ a difference bet'een enolate and hydroxide 04 $nit

Thermodynamic e.$ilibri$m! )oes to more s$bstit$ted al1enetereochemistry for intermediate yn aldol  Anti aldol

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ome p/ a *al$es

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Controllin) the Aldol

ormation of enolate Thermodynamic enolate /inetic enolate

(ase -

H!-

&!-

H!-

& 26 Thermodynamic conditions /inetic conditions

ee7 8" r)" Chem"! 1963! 28! 33%29 8" r)" Chem"! 1965! 30! :34:9

8" r)" Chem"! 1965! 30! 25;29 8" r)" Chem"! 1969! 34! 2324

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/inetic *ers$s Thermodynamic Enolate

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E and < Enolates

= >E? >

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,eneral eat$res of Enolate E.$ilibri$m

E.$ilibri$m position determined by7 sol*ent! base!cation! temperat$re

/inetic Enolate Thermodynamic Enolate Aprotic sol*ents Et2!

TH6

rotic ol*ents &H6

tron) bases BA! BTM6 Dea1er bases &-! H-6

xophilic cations Bi! Ti4!

(3

! Al3

6Bo' Temperat$re -# FC6 Hi)her temperat$re G;FC6

hort reaction time Bon) reaction time

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(ase Effect on Enolate ,eometry 

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 Acyl Addition Models

el1in-Anh

 Anti el1in-Anh

Cram

Cram Chelate J. Am. Chem. Soc.! 1952! 74! 5#2#9 J. Am. Chem. Soc.! 1953! 75 !

%;;59 J. Am. Chem. Soc.! 1963! 85 ! :245

 J. Chem. Soc.! 1959! ::29 Tetrahedron Letters! 1968!2:@@9 Tetrahedron Letters,  1976, :55

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,eneral bser*ations

&eaction sometimes hi)hly stereospecific

tereospecific 'hen & lar)e

ome e.$ilibration or isomerization

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Examples

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The Main roblem

β-Hydroxy carbonyls dehydrate to form α!β-$nsat$rated carbonyls Thermodynamically more stable prod$ct Happens thro$)h E: elimination of the conI$)ate base E:cb6

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The +n*esti)ated &eaction

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roced$re

Mix 5"3 ) benzaldehyde 'ith :"45 ) acetone

 Add half to sol$tion of 5 ) aH in 5; mB 'aterJ4; mB ethanol

tir :5 min$tes

 Add remainder of benzaldehydeJacetone sol$tion

tir 3; min$tes Kac$$m filter crystals

 Dash crystals 'ith :;; mB 'ater

&epeat 3x

ress dry 'hile *ac$$m applied&ecord 'ei)ht! mp! +&! L yield

&ecrystalize 'ith ethanol if necessary 

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re-Bab Thin)s

+ncl$de &eactions Mechanism Hazards ensities Molec$lar 'ei)hts of startin) material and prod$ct

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ost-Bab Thin)s

Thin)s to thin1 on /inetic or thermodynamic conditions

 Dhat 'o$ld happen if yo$ ran this reaction $nder the otherconditions

Ho' 'o$ld yo$ r$n the reaction $nder the opposite conditions +s prod$ct trans!trans! cis!trans! or cis!cis

Ho' do yo$ tell

Ho' 'o$ld yo$ form the intermediate aldol prod$ct

 'itho$t dehydration

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,ettin) $t on Time

 Dor1 in pairs

'itch bet'een *ac$$m flas1s 'hen 2J3 f$ll

ry prod$ct thoro$)hly on *ac$$m for mp and +&