Aldehydes and Ketones Upto Wittig

Ketones and Aldehydes  Carbonyl Structure Carbon is sp2 hybridized. C=O bond is shorter, stronger, and more polar than C=C bond in alkenes. => 2  Naming Aldehydes IUPAC: Replace -e with -al. T...

Ketones and Aldehydes  Carbonyl Structure Carbon is sp2 hybridized. C=O bond is shorter, stronger, and more polar than C=C bond in alkenes. => 2  Naming Aldehydes IUPAC: Replace -e with -al. The aldehyde carbon is number 1. If -CHO is attached to a ring, use the suffix -carbaldehyde. => 3  Examples CH3 O CH3 CH2 CH CH2 C H 3-methylpentanal CHO 2-cyclopentenecarbaldehyde => 4 Aldehydes: Common Names O O O O H C H H3C H H3C CH2 C H H3CH2CH2C C H Common Formaldehyde Acetaldehyde Propionaldehyde Butyraldehyde IUPAC Methanal Ethanal Propanal Butanal Cl O HO O O H3C CH H C H H3CHC=HC C H 2-Chloropropanal 3-Hydroxypropanal 2-Butenal Aromatic aldehydes are usually designated as derivatives of the simplest aromatic aldehyde, Benzaldehyde Benzaldehyde p-Nitrobenzaldehyde o-Hydroxybenzaldehyde p-Methoxtbenzaldehyde Salicylaldehyde Anisaldehyde O OH O O O H H H H O 2N H3CO  IUPAC Names for Ketones Replace -e with -one. Indicate the position of the carbonyl with a number. Number the chain so that carbonyl carbon has the lowest number. For cyclic ketones the carbonyl carbon is assigned the number 1. => 6  Examples O O CH3 C CH CH3 CH3 Br 3-methyl-2-butanone 3-bromocyclohexanone O CH3 C CH CH2OH CH3 4-hydroxy-3-methyl-2-butanone => 7  Name as Substituent On a molecule with a higher priority functional group, C=O is oxo- and -CHO is formyl. Aldehyde priority is higher than ketone. COOH O CH3 O CH3 C CH CH2 C H CHO 3-methyl-4-oxopentanal 3-formylbenzoic acid => 8 Common Names for Ketones Named as alkyl attachments to -C=O. Use Greek letters instead of numbers. O O CH3 C CH CH3 CH3CH C CH CH3 CH3 Br CH3 methyl isopropyl ketone a-bromoethyl isopropyl ketone O O O OH => CHO C2 H 5 C C2 H 5 Cyclopentylpropanone 3-Ethyl-2-hydroxycyclohexanone 5-Oxohexanal 9  Historical Common Names O C O CH3 CH3 C CH3 acetone acetophenone O C benzophenone => 10  Boiling Points More polar, so higher boiling point than comparable alkane or ether. Cannot form H-bond to each other, so lower boiling point than comparable alcohol. => 11  Solubility Good solvent for alcohols. Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O-H or N-H. - + O + -     C O H H O C Acetone and acetaldehyde are miscible in water. 12 =>  Industrial Importance Acetone and methyl ethyl ketone are important solvents. Formaldehyde used in polymers like Bakelite. Flavorings and additives like vanilla, cinnamon, artificial butter. => 13  Preparation of aldehydes and ketones 1- Oxidation of alcohols CrO3/ pyridine O Other reagent: RCH2 OH R Cu / heat H O CrO3/ pyridine R2CH OH R C R Cu / heat 2- Reduction of acid chloride O H2 / Pd(BaSO4) R-H 2C-C R-CH2-CHO Cl Rosenmund’s reduction O O LiAlH[O(CH3)3] 3 Cl H OR 3- Ozonolysis of alkenes A A 1)O 3 A A 2)Zn / H 2O A O + O A A A 4- Hydration of alkynes (Kocherov’s reaction) H H H2SO4, HgSO4 C C + HO H C C C C OH H O an enol unstable carbonyl more stable 4a. Hydroboration-oxidation -78 C H 3C C CH + (Sia)2BH CH3-CH=CH ether O (Sia) 2BH H 2O2/ OH - CH3-CH 2-CH H 2O CH 3 CH 3 Sia= CH 3-C C : disiamyl H H  Kucherov Reaction Hydration of terminal alkynes affords ketones Useful for symmetrical alkynes only Mikhail Kucherov, 1881-1883 HgSO4, dil. H2SO4 in EtOH Mechanism 16 Chapter 18  5- Friedel Crafts acylation O O CH3 AlCl 3 + R Cl 6-Oxo reaction - Hydroformylation reaction CH3-CH=CH2 + H2 + CO CH3-CH2-CH2-CHO + CH3-CH-CH3 CHO 75 % 25 % Catalyst: Example: 7- Gattermann-Koch reaction CHO AlCl3 + HCl + CO Mechanism 18 7a. Reimer–Tiemann reaction A chemical reaction used for the ortho- formylation of phenols Mechanism 19  8- Oxidation of an Alkyl Side of aromatic ring H3 COCO OCOCH3 CH 3 HC CHO CrO3 / 10 C H2O / H+ (CH3CO)2O 9- From acid chloride and lithium dialkyl cuperate or R2 Cd O O R2CuLi -78 C R C Cl + R C R2 O ether O -78 C C Cl + (CH3-CH2)2CuLi C CH2 -CH 3 ether O O -78 C H3 C C Cl + (Ph)2Cd C CH 3 ether 10- Ketones From nitrile and Grignard reagent or alkyl lithium NMgX O Ether H3O+ R C N + R'MgX R C R' R C R' NLi O Ether H3O+ R C N + R'Li R C R' R C R' O CH 3 H 3C H 1) Ether H C C N + PhLi C C H 3C 2) H3O+ CH 3 11. Ketones from Carboxylates Organolithium compounds attack the carbonyl and form a diion. Neutralization with aqueous acid produces an unstable hydrate that loses water to form a ketone. Example Mechanism First step in the reduction of carboxylic acids with organolithium compounds 22 Second step in the reduction of carboxylic acids with organolithium compounds 12. Synthesis from acetoacetate ester CH3-CO-CH2-COOEt Attachment of ketomethyl group active methylene group General scheme R1 R1 CH3-CO-CH2-COOEt CH3-CO-C-COOEt CH3-CO-C-H Example R2 R2 Base: NaOMe, NaOH, K2CO3 Mechanism 23 13. Synthesis Using 1,3-Dithiane Remove H+ with n-butyllithium. BuLi S S S S _ H H H Alkylate with primary alkyl halide, then hydrolyze. + O CH3CH2Br H , HgCl2 C S S S S H2O H CH2CH3 _ /CdCO3 H CH2CH3 => H 24 Ketones from 1,3-Dithiane After the first alkylation, remove the second H+, react with another primary alkyl halide, then hydrolyze. + O BuLi CH3Br H , HgCl2 S S S S C S S _ H2O CH3 CH2CH3 CH3 CH2CH3 H CH2CH3 CH2CH3 => 25 14. Preparation of aldehydes and ketones from calcium salts Mechanism 26 Process: Dry distill Ozonolysis The unsaturated bonds of alkenes, alkynes, azo compounds are cleaved by ozone. Alkenes and alkynes form carbonyl compounds based on reductive or oxidative work up. Mechanism Zn/H2O or Me2S or example H2O2/OH- ozonide H2O O 27 15. Preparation of ketone from osmate ester Reagent: OsO4 (2 mol%) NMO (>1 equiv) Reagent: NaIO4 or Pd(OAc)4 28  Nucleophilic Addition A strong nucleophile attacks the carbonyl carbon, forming an alkoxide ion that is then protonated. A weak nucleophile will attack a carbonyl if it has been protonated, thus increasing its reactivity. Aldehydes are more reactive than ketones. H R R C+ O - > C+ O - > C+ O - H H R' Reactivity of the carbonyl group 29 =>  Geometry of Nucleophilic Attack on Carbonyl The sp2 hybridization of the carbonyl compound means that attack of the nucleophile on the carbonyl carbon may occur from either face. The resulting addition product is sp3-hybridized. 30  Equilibria in Carbonyl-Addition Reactions Carbonyl addition reactions are reversible. The extent to which the reaction is able to proceed is defined by the magnitude of the equilibrium constant: 1. Water addition 31  Equilibria in Carbonyl-Addition Reactions ❑ Reactant Stability: – Recall that alkyl groups stabilize double bonds (more highly substituted alkenes are more stable than less substituted alkenes) – This works for C=O double bonds, too. – Ketones are more stable than aldehydes – Therefore, the addition to ketones is less favored than addition to aldehydes ❑ Product Stability: – The four groups in the product are closer together than the three groups attached to the carbonyl carbon in the reactant. – Alkyl groups cause more steric destabilization in the tetrahedral addition product than does hydrogen – Therefore, the ketone addition product is less favored than the aldehyde addition product  2- Addition of alcohols: O R'O R'O + R''OH H R C 2 + R'OH R C 2 OH H + R C OR'' R catalyzed only by R 2 2 catalyzed only R R =H: Aldehyde acid or base Hemiacetal Acetal by acid 2 Ketone R =Alkyl Hemiketal Ketal O HO H5C2O + H H3C C + C2H5OH H3C CH OC2H5 C2H5OH H3C CH OC 2H5 H + Hemiacetal H Acetal O HO H5C2O + H H3C C + C2H5OH H3C C OC 2H5 C2H5OH H3C C OC 2H5 CH3 + H CH3 CH3 Hemiketal Ketal Hemiacetals or hemiketals are unstable and can’t be isolated in most cases, whereas acetals and ketals are stable.  Mechanism of Acetal Formation Under acidic conditions, some of the alcohol becomes protonated ROH2+. The hemiacetal OH oxygen abstracts a proton from ROH2+. Loss of water gives a resonance-stabilized alkoxy carbocation. Nucleophilic attack by the alcohol on the carbocation occurs. Deprotonation by a further alcohol molecule produces the acetal. 34  Cyclic Hemiacetals Cyclic hemiacetals containing five and six atoms in the ring can form spontaneously from hydroxyaldehydes: Five and six-carbon sugars are important biological examples of cyclic hemiacetals: 35  Acetals as Protecting Groups Protecting groups are functional groups which may be introduced in a molecule by converting another functional group in a reversible reaction. If the protecting group is more inert than the original functional group, then other reactions may be carried out with this molecule without worrying about altering or destroying the protecting group. When the other desired reactions are completed, the original group may be restored by carrying out the reverse of the reaction which introduced the protecting group. ❖ The reversibility of acetal formation along with the relative inertness of the RO-C-OR linkage make acetals useful as protecting groups.  Acetals as Protecting Groups Acetaldehyde forms a cyclic trimer when treated with acid: Hydrolyze easily in acid, stable in base. Aldehydes more reactive than ketones. O O CH2 CH2 HO OH + O H H C C O O => 37  Acetal as protecting group ❑ Note that there are essentially three requirements for an effective protecting group. It must be formed in high yield In the protected form it must be unreactive The protected functionality must be efficiently re- converted to the original functionality. This step is called “de-protection”. ❑ The de-protection step is very facile in the case of an acetal, because in the course of acidic, aqueous workup it is quickly hydrolyzed to the carbonyl functionality. How do we convert 38  Cyclic Ketals Addition of a diol produces a cyclic ketal. Usually diols are used as the protecting group. CH2 CH2 O O O H+ CH2 CH2 + HO OH cyclohexanone Ethylene glycol => 39  Selective Reaction of Ketone React with strong nucleophile (base) Remove protective group. + _ O MgBr O CH3 HO CH3 + CH3MgBr H3O O H O C C C O O O => 40 3- Addition of Hydrogen Cyanide: Formation of cynohydrins R' O R C R' + HCN R C OH CN Cyanohydrin NH2 CN O OH OH H H2 / Pt + HCN or LiAlH4 and H 3O + Benzaldehyde cyanohydrin OH O OH + H3O COOH + HCN CN Heat HCN is highly toxic. Use NaCN or KCN in base to add cyanide, then protonate to add H. Reactivity formaldehyde > aldehydes > ketones >> bulky ketones. 4- Addition of acetylide ions: NaNH2 2 R H R2 C R' O + Na 2 - + H3 O 2 R C R' + R C C Na R C C C R OH O OH + - + H3 O + H3C C C Na C C CH3 ❑ Since terminal alkynes are unusually acidic, their conjugate bases may be prepared quantitatively by using a sufficiently strong base. In this connection, sodium amide is an appropriately strong base (the pKa’s of terminal alkynes are ca. 25, whereas the pKa of ammonia is ca. 38). ❑ These anions are carbon centered anions (carbanions), and, like Grignard reagents, are highly nucleophilic. They therefore add in the same manner as do Grignard reagents to carbonyl compounds. 42 5- Addition of Grignard Reagents: Formation of alcohols R' O 1) Dry ether R C + R'MgX 2) H 2O R CH OH H HO O 1) Dry ether H3C C + C2H5MgX 2) H 2O H3C CH C2H5 H R' O 1) Dry ether R C R' + R''MgX 2) H 2O R C OH R'' CH3 O 1) Dry ether + CH3MgX 2) H 2O OH  6. Formation of Imines Nucleophilic addition of ammonia or primary amine, followed by elimination of water molecule. C=O becomes C=N-R CH3 CH3 H3C R R _ RNH2 C O H2N C O N C OH Ph + Ph H Ph CH3 CH3 R R H2 -H2O N C N C OH Raney Ni RNH CH(CH3)Ph H Ph Ph => 44 Schiff’s base Other Condensations 45 =>  Reduction Reagents Sodium borohydride, NaBH4, reduces C=O, but not C=C. Lithium aluminum hydride, LiAlH4, much stronger, difficult to handle. Hydrogen gas with catalyst also reduces the C=C bond. => 46 Catalytic Hydrogenation Widely used in industry. Raney nickel, finely divided Ni powder saturated with hydrogen gas. Pt and Rh also used as catalysts. O OH Raney Ni H => 47 Meerwein–Ponndorf–Verley reduction The Meerwein–Ponndorf–Verley (MPV) reduction is the reduction of carbonyl compounds to their corresponding alcohols utilizing aluminum alkoxide catalysts in the presence of a sacrificial alcohol (e.g. isopropanol) ✓ Chemoselectivity: MPV reduction is chemoselective. Aldehydes are reduced before ketones ✓ Stereoselectivity: can be performed on prochiral ketones leading to chiral alcohols ❑ While commercial aluminium isopropoxide is available, the use of it often requires catalyst loadings of up to 100-200 mol%. ❑ There are several known side reactions. 48 Meerwein–Ponndorf–Verley reduction Stereoselective MPV 1. Chiral catalyst 2. Chiral catalyst Other recent examples 49 Meerwein–Ponndorf–Verley reduction Mechanism 50  Oppenauer oxidation Oppenauer oxidation, named after Rupert Viktor Oppenauer is a gentle method for selectively oxidizing secondary alcohols to ketones. It is just opposite to MPV reduction. Recent Literature 51  Deoxygenation Reduction of C=O to CH2 Two methods: Clemmensen reduction if molecule is stable in hot acid. Wolff-Kishner reduction if molecule is stable in very strong base. => 52  Clemmensen Reduction Erik Christian Clemmensen, a Danish chemist The Clemmensen Reduction allows the deoxygenation of aldehydes or ketones, to produce the corresponding hydrocarbon. Examples O C CH2CH2CH3 CH2CH3 Zn(Hg) HCl, H2O O Zn(Hg) CH2 C CH2 CH3 H HCl, H2O 53 Mechanism of Clemmensen Reduction 54  Wolff-Kisher Reduction Form hydrazone, then heat with strong base like KOH or potassium t-butoxide. Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMSO. Wolf in 1912 heated ethanolic solution of hydrazones to 180 °C in the sealed tube along with sodium ethoxide. CH2 C H CH2 C H KOH CH2 CH3 H2N NH2 heat O NNH2 Chemoselectivity O N-NH 2 NH2NH2 COOH COOH H H NaOH 55  COOH  Huang Minlon Modification ▪ It is the modified Wolf-Kishner reduction reported by Huang Minlon in the year 1946, to overcome the limitations of the original reaction. The refluxing the carbonyl substrate with 85% hydrazine hydrate and sodium hydroxide in ethylene glycol. Ethylene glycol is used as it has high boiling point removes nitrogen gas which is produced as a side product in the reaction. Advantages like the production of pure products with increased yield than the original reaction. It can be also used for sterically hindered ketones. 56 Oxidation of Aldehydes Easily oxidized to carboxylic acids. => 57  Tollens Test Add ammonia solution to AgNO3 solution until precipitate dissolves. Aldehyde reaction forms a silver mirror. O O + _ H2O _ R C H+ 2 Ag(NH3)2 + 3 OH 2 Ag + R C O + 4 O + _ H2O _ NH3)2 + 3 OH 2 Ag + R C O + 4 NH3 + 2 H2O => 58  Iodoform reaction A chemical reaction in which a methyl ketone is oxidized to a carboxylate by reaction with aqueous HO- and I2. H3C O C O + 3 I2 + 4 NaOH R O Na - + + CHI3 + 3 NaI R CH3 I 2 / NaOH H3C H3C COONa + CHI3 O Ketone halogenation The position alpha to the carbonyl group in a ketone is easily halogenated, due to the ability to form an enolate in basic solution, or an enol in acidic solution. In acidic solution, usually only one alpha hydrogen is replaced by a halogen, because each successive halogenation is slower than the first. Reagent: Br2/AcOH Cannizzaro reaction Sanislao Cannizzaro, Italian scientist, in 1853 Aldehyde which does not contain α hydrogen undergoes Cannizzaro reaction. This redox disproportionation of non- enolizable aldehydes to carboxylic acids and alcohols is conducted in concentrated base. NaOH or KOH as base Mechanism of the Cannizzaro Reaction rate = k[RCHO]2[OH−] (follow a 3rd order kinetics) Proof of Hydride Transfer: when ArCHO is made to react in D2O no D is incorporated in the CH2 group indicating that H (or D) transferred directly from one to another aldehyde Crossed Cannizzaro Reaction An interesting variant, the Crossed Cannizzaro Reaction, uses formaldehyde as reducing agent: Today the Cannizzaro Reaction has limited synthetic utility as one of the products is not the desired product Recent Literature Lithium Bromide as a Flexible, Mild, and Recyclable Reagent for Solvent -Free Cannizzaro, Reactions Org. Lett., 2007, 9, 2791-2793. Enantioselective Intramolecular Cannizzaro Reaction, J. Am. Chem. Soc., 2013, 135, 16849  Aldol Reaction Discovered independently by the Russian chemist Alexander Borodin in 1869 and by the French chemist Charles-Adolphe Wurtz in 1872. ❑ The aldol reaction is one of the most important carbon–carbon bond forming reactions in organic chemistry. ❑ The reaction combines two carbonyl compounds react in presence of acid or base to form a new β-hydroxy carbonyl compound ❑ 'Aldol' is an abbreviation of aldehyde and alcohol. 63  Aldol Reaction ❑ The aldol reaction unites two relatively simple molecules into a more complex one ❑ The minimum requirement is the presence of at least one a hydrogen ❑ Up to two new stereogenic centers (on the a and b carbon) of the aldol adduct ❑ Once formed, the aldol product can lose a molecule of water to form an a,b-unsaturated carbonyl compound, called aldol condensation. A disadvantage: It should be noted that the product is still a carbonyl compound and may undergo further reaction. Thus a low molecular weight polymer may also be formed. 64 Aldol Reaction: Mechanism Important attribute Carbonyls: Weak Acids At The a-Position O CH2 CH3 H H H pKa = 15-20 pKa = 44 pKa = 60+ CH3 O CH2 localized anion O 65 Reminder – alcohols have a 15-20 pKa range! Aldol Reaction: Mechanism Say acetaldehyde is the substrate Base catalyzed Acid catalyzed 66 Aldol Reaction: Mechanism Step 1: enolate formation Zimmerman–Traxler model 67  Crossed Aldol Reactions: Non-Enolizable Aldehydes H O H H H O H3O+ O O H Ph O OH O OH Acidic: Me Me Me Me Me CH2 Me Ph Me Ph a b-hydroxy carbonyl O –OH O O H2O O OH O O H Ph Basic: H2O Me Me Me CH2 Me Ph Me Ph a b-hydroxy carbonyl  Crossed Aldol Reactions: Enolizable Aldehydes H O O O H3O+ OH OH O OH O OH H Me + + + Me Me H Me Me CH2 H CH2 Me H H H Mixture of Aldol Addition Products Aldol Reactions With Unsymmetrical Ketones O O –OH O O O OH O + H Ph + Me Me Me Me Me Me CH2 Me HPh Me HO Ph Less stable, less hindered More stable, more hindered Mixture of Aldol Addition Products  Some examples H3C O OH dil. NaOH 2 C O R C CH2 C R R CH3 CH3 dil. NaOH H3C CH3 2 H3C O OH O CH3 71  The Aldol Condensation H O OH O H3O+ O OH E2 Acidic: Me Ph R Ph R Ph a b-hydroxy carbonyl H an a,b-unsaturated carbonyl OH2 O OH O E2 Basic: R Ph R Ph H an a,b-unsaturated carbonyl –OH  O How can we make this compound from a linear precursor? H Retrosynthesis synthesis Intramolecular Aldol Condensation O O Na2CO3, H2O O heat O (96%) via: OH even ketones give good yields of aldol condensation products when the reaction is intramolecular 74  Aromatic Aldehydes O O CH3O CH + CH3CCH3 NaOH, H2O 30°C O CH3O CH CHCCH3 (83%) Perkin reaction The Perkin reaction is another long known organic reaction developed by British scientist William Henry Parkin in 1868. It gives an α,β-unsaturated aromatic acid by the aldol type condensation of aromatic aldehydes with acid anhydride in the presence of an alkali salt of the same acid OH 76 Perkin reaction: Mechanism Formation of anhydride enolates. aldol type reaction provides the alkoxide anhydride. Intermolecular acylation generates an acetoxy carboxylate, which forms a mixed anhydride. Elimination of acetic acid and subsequent hydrolysis gives the unsaturated acid. 77 The Claisen Condensation Reaction. (In 1887) Base-promoted condensation of two esters to give a b-keto-ester product Rainer Ludwig Claisen R2CHCOOEt + Ph3C R2C-COOEt X No Claisen product 2 a protons are important 78 Crossed Claisen Condensations. Similar restrictions as the mixed aldol condensation. Four possible products Esters with no a-protons can only act as the electrophile Discrete (in situ) generation of an ester enolate with LDA 79 Intramolecular Claisen Condensation: The Dieckmann Cyclization. (in 1894) Dieckmann Cyclization works best with 1,6- diesters, to give a 5-membered cyclic b-keto ester product, and 1,7-diesters to give 6-membered cyclic b-keto ester product. Mechanism: same as the Claisen Condensation 80 Acylation of Ketones with Esters. An alternative to the Claisen condensations and Dieckmann cyclization. Equivalent to a crossed Claisen condensation Equivalent to a Dieckmann cyclization 81 The products of a Claisen condensation or Dieckmann cyclization are acetoacetic esters (b-keto esters) which can be further utilized for carbonyl synthesis like EAA 82 Knoevenagel Condensation The condensation of active methylene compounds (AMCs) with aldehydes to afford α,β-unsaturated compounds. Doebner Modification: In the presence of carboxylic acid groups, it includes a pyridine-induced decarboxylation. 83 Knoevenagel Condensation: Mechanism Knoevenagel Condensation: Recent literature Refer to: https://www.organic-chemistry.org/namedreactions/knoevenagel-condensation.shtm Stobbe Condensation The Stobbe condensation is a modification specific for the diethyl ester of succinic acid requiring less strong bases. The product is an a,b-unsaturated ester with an acid attached to the product. [or b,g-unsaturated acid with an ester at b-position.] Mechanism 86 Benzoin Condensation The Benzoin Condensation is a condensation between two aldehydes devoid of any α-hydrogen in the presence of a catalyst (e.g. CN-) for the preparation of α-hydroxyketones. The first method was reported by Leibig and Wohler in 1832 using benzaldehyde to form benzoin as the product. The mechanism was established only in 1903 by A. J. Lapworth. 87 Benzoin Condensation: Mechanism Addition of the cyanide ion to create a cyanohydrin effects an umpolung of the normal carbonyl charge affinity, and the electrophilic aldehyde carbon becomes nucleophilic after deprotonation A strong base is now able to deprotonate at the former carbonyl C-atom Rate = [ArCHO]2[CN-] A second equivalent of aldehyde reacts with this carbanion; elimination of the 88 catalyst regenerates the carbonyl compound at the end of the reaction. Benzoin Condensation: Examples An intramolecular asymmetric benzoin condensation An intermolecular asymmetric benzoin condensation 89 Benzoin Condensation: Recent Literature Refer to: https://www.organic-chemistry.org/namedreactions/benzoin- 90 condensation.shtm Benzilic acid rearrangement Oxidation of benzoin to benzil or HNO3 The benzilic acid rearrangement is formally the 1,2- rearrangement of 1,2-diketocompounds to form α- hydroxycarboxylic acids in the presence of a base. 91 Benzilic acid rearrangement: Mechanism OH- ? 92  Wittig Reaction Nucleophilic addition of phosphorus ylides. Product is alkene. C=O becomes C=C. First report: 1953, Wittig and => Geissler, Liebigs Ann. 1953, 93 580, 44  Phosphorus Ylides Prepared from triphenylphosphine and an unhindered alkyl halide. Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus. + _ Ph3P + CH3CH2Br Ph3P CH2CH3 Br _ + + BuLi Ph3P CH2CH3 Ph3P CHCH3 ylide => 94  Mechanism for Wittig The negative C on ylide attacks the positive C of carbonyl to form a betaine. Oxygen combines with phosphine to form the phosphine oxide. + _ Ph3P O- + H3C Ph3P CHCH3 C O H C C CH3 Ph CH3 Ph + _ Ph3P O Ph3P O Ph3P O H CH3 H C C CH3 H C C CH3 C C H3C Ph CH3 Ph CH3 Ph betaine Oxaphosphatane => 95 (a (+)vely charged (an intermediate) cationic functional group) Possible to detect sometime at low temp. Wittig reaction: examples Industrial preparation of Vitamin A (BASF, 1956)