Assignment No 2 Topic: Enolization Course code: CHEM-522 Submitted By: Zunaira Arshad 17101707-043 M.Phil B Submitted To: Dr.Sajjad Sumerra EnolisationDefinition: A process in which an aldehyde or ketone is converted into its respective Enole is called enolization or keto-enol tautomerism.
 Chemistry of Carbonyl compoundvNature of carbonylcompound and Reactivity;Carbonyl compound is very versatileand it contains partial positive charge on carbon and partial negative chargeon oxygen. Important points in its chemistryare;1.Carbon and Oxygen are sp2 hybridized2.Carbon form single bond with other R groups3.Two lone pairs are present on oxygen atomThe geometery or framework ofcarbonyl compound is TrigonalPlanner. While the reactivity of carbonyl compound is dueto the presence of acidic ?-hydrogen. Since in alkanes hydrogen is bondedto carbon by sp3 hybridization but the electronegativity differencebetween carbon and hydrogen is so smalldue to which the attatched hydrogen is less acidic.While in the case ofaldehyde or ketone due to the presence of carbonyl group to the ?-carbon the?-hydrogen becomes more acidic.
But stillthis ?-hydrogen is less acidic then hydrogen of H2O. CH3CH3 Actually two main factorsresponsible for acidity of carbonyl compounds are;1. Inductive effect ofcarbonyl compound increases the pocitivecharacter of ?-hydrogen2.
Resonancestabilization of conjugate baseSince above values shows thataldehyde and ketones are more acidic then sp3 hybridized Carbon as alkanes.BecauseAfter the removal of ?-hydrogen the conjugate base formed is more stable incarbonyl containing compounds due to resonance than sp3 hybridizedcarbon. Similarly aldehyde and ketone aremore acidic than ethers for the same reason which is described above and ethersare less acidic because after removal of ?-hydrogen in ethers the non-bondingelectrons of OR and O compete for resonance. When ?-hydrogen is present betweentwo carbonyl compounds then pka of ?-diketoester is more then pka value of ?-Diketones i.e?-diketoester is less acidic then ?-dietones.
Enol and Enolate anion;An enol is such intermediatestructure which has alkene attatched with OH group As en for alkene and ol for alcohol. While when carbonyl compound losses its alpha-proton the resulting ionformed is called Enolate anion Enolization‘When carbonyl compound afterlossing alpha-hydrogen changed into enol’ enolEnolization in neutral media is aslow process so we do enolization inacidic or Basic media. Typesof Enolization:1. Acid catalysed Enolization: Step 1: Transferof proton from acid to oxygen of carbonylcompound.
Protonation increases acidity of alpha-hydrogen nowa neutral or weak Basic solvent easily can accept proton from acid. Step 2: Proton is removed from alpha-C of carbonyl compound by abronsted Base H2O. 2. Base catalysed Enolization: Step1: Alpha-hydrogen of carbonyl compd removed by base Step 2: Proton transfer to carbonyl oxygen bybronsted acid as H2O Difference between above two types is that thesteps involve are reverse.
As proton abstraction is first step in base catalysedenolization while it is second step in acid catalysed enolization.But thesimilarity in both steps is that the rate determining step is that where abstraction occur.Second similarity is thatboth consist of two steps.Mobile’ Carbonyl compd behaves electrophile as well as nucleophile as they exist in twoFormsone is carbonyl containing i.e electrophile while other is enol form thatbehaves as Nucleophile.
Experimental proof ofketo-enol form; ItsIUPAC name is DIMEDONEKetoform has 4 peaks for OH, keto gp,c-c,c=c.but above structures can be studied in these ways.1.IR2.1HNMR3.
13CNMRIN IR Functional group region: Forketo form peaks for C-H,C-H(out of ring),C-C,C=O(sharp) form but in enol formin addition to above four C=C,OH (broad)will also appear.IR: Tellsthat in practice peaks for C-H(in ring),C-H(out of ring),C-C,C=O observe but inactual practice C=C,OH(broad) are found (finger print region).it means bothcompounds are present C=O keta and OH enol form.1HNMR: Gives 3 1HNMR peaks for keto form and 5 in case of enolform.Total 7 peaks appear because bothpeaks for CH3 combine and their intensity increases.1HNMRshows it is not a pure compound but both keto and enol forms exists. 13CNMR: INketo form it gives 5 peaks while in enol form it gives 7 peaks.But 5 carbon ofketo and 7 carbon of enol overlap and gives 10 peaks total.
We cannot purify orseparate these compounds but which product form depends on predominantform of compound. Sinceenolization is transfer of proton from carbon to oxygen still it has no effecton pH.Why enolizationshifted towards carbonyl compounds?Sinceequilibrium shifts towards more stable reactant.e.
g simple carbonyl compoundsas acetone have traces of enol under ordinary set of conditions so equilibriumlies well towards carbonyl compound.Thisis due to C-H,C=C,C=O combination is less stable than Combinationof C=O,C-H bondhere balance between bond energies is quite fine .On one hand OHbond in enol is stronger than C-H.But on other hand C=O is more stable than C=C.So under normalconditions in a solution one part of enol is present in hundred parts ofketone.Ketone is more stable than enolby some45-60kJ/mol the reason behind isthe C=O stronger bond than C=C bond. Stabilized enols: Some structural features stabilizes the enol formmore stable.
e.g phenolic form of 2,4-cyclohexadienone than keto form by gaining aromatic ring structure. Similarly1,3 arrangement of two carbonyl group in diketone makes the enol form morestable due to1.conjugationof double bond with carbonyl group 2.intermolecular hydrogen bonding Requirement of Enolization( on basis oforbital): Any organic compound with 1 electronwithdrawing functional groupwith at least 1 pi-bond joined to such saturatedcarbon atom and also having at least 1 H-atom can form enol in acidic orneutral media.
Some form enol in basic media with exceptions beingcarboxylic acid,primary and secondary amines. The enolate ion is justlike an alkoxide ion but more stable than corresponding saturated one becauseit is conjugated. One important difference between enol and enolates is that th delocalizationin later.This delocalization actually cause of its stability.
The oxyanionand carbanion structures are just two ways of representingsame thing and this thing can be visualized on the basis of orbitals. Consider thepi-orbitalof allyl anion and enolate ion. Populated pi orbital of an allylanion Populate piorbital of an enolate Reactive HOMO Reactive HOMO Allyl anion is more stable and in enolate ion 1 carbon of allyl anion replaced by anoxygen.This replacement result in 2 important changes.1.Dueto more electronegativity of O2both orbitals goes down in energy.
2.Theorbitals are distorted. The lower energyatomic orbitals of more electronegative O2 contributes to the more energetic orbitals less to . Charge distribution comesfrom both populated orbitals so negative charge spread over all the 3 atoms but mostly on ends.The important reactive orbital is HOMO which has large orbital on terminal carbon.
In theenolates the oxygen atom has the more ofnegative charge but carbon atom has moreof the HOMO.In other words we can say oxygen is hard nucleophilic centre whilecarbon is soft centre.Here the reactionswhich dominated by charge andelectrostatic interactions will occur onoxygen and those dominated by orbital interactions occur on carbon. Thus acyl chloride tend to react onoxygen to give ester while allyl halide tend to react on carbon. Enolequivalents: Compounds other thancarbonyl group can aiso similar reactions called enol equivalents.
e.g imines,enamine also show similar tautomerism. Some are thermodynamic enolates whichpredominates in thermodynamic control conditions.
Thesenolates are more substituted and more stable while kinetic enolates are thoseformed faster These occur in aprotic solvent and they remove the less hindered alpha-hydrogen In primary amine (aniline) stable imineis formed but in secondary amine(cyclic structure) iminium salt formed which isless stable than enamine.(b)Azo enolates: As enamine is nitrogenanalog of enol azo enolates made bydeprotonation of enamine with strong base. Similarly nitroalkane form enolate like anion which are quite weak bases.Here basecatalysed enolization by transfer ofproton stable oxyanion is formed.In CH3NO2 Nitriles(cyanides): Strong base is needed here.The negative charge is delocalized b/w nitrogen and carbon of nitroalkane .The resulting anion is 3 atoms 4 electron system just as ketone orallene. (d) cyclic compounds: Cyclic ketones can also form enol andenolates Similarly cyclic aldehydes also formenols and enolates anions Enolization and syntheticroutes: 1.
The carbonyl group is accepting proton in enolization and nucleophilic attack. 2.The same compd which iselectrophilic are easily ionizable.Hence acyl halides are easily ionizable. 3.To avoid nucleophilicattack we cannot use Cl- ionas base.So nucleophilic base like tri amine should used. 4.
The resulting enolate isunstable and eliminate Cl- or halide ion, agood leaving group for“ketone” formation. COMMENT: “This is best method forpreparation of dichloroketone from dichloroacetylchloride as the proton removedis very acidic” In basic medium the carboxylic acid do notform the enolate anion easily.Here in basic media 1st proton isremoved .This thing protects the acids from the attack bynucleophile. E.g In acidic solution no such problem occur and“ene-diole” formed.
The original OH groupfrom acid and new OH group of the enols are equivalent REACTIONS THAT PROCEED VIA ENOL OR ENOLATES: These important reactions are given by1.Alphahalogenations of carbonyl compounds: It is type of substitutionreaction.The hydrogen of carbonyl is nottake part in reaction only alpha- hydrogen is take part in reaction.thesolvents used are water chloroform,acetic acid,diethyl ether etc. In acidic media Mechanism In Basic media: The difference between acidic and basic mediais that in acidic media electron withdrawing halogen decreases the basicity ofoxygen of carbonyl compound by protonation while in basic media halogen increases the acidity of alpha-hydrogenthat’s why halogenations is faster and favourable in basic media than acidicmedia. Haloform Reaction: Methyl ketone reaction in presence of excess halogen andbase Haloform prepared .
Inthis reaction enolate ion involve. Nucleophilicsubstitution: Enolate form give nucleophilicsubstituted product. Alkylation: Enolates can also give alkylated products.Second reactionis useful in regioselective using LDA with ketone. BIOLOGICAL IMPORTANCE OF ENOLATES: