Aldehydes Ketones Nucleophilic Addition Reaction ALDEHYDES KETONES Before

Aldehydes &Ketones Nucleophilic Addition Reaction

ALDEHYDES & KETONES Before you start it would be helpful to… • know the functional groups found in organic chemistry • know the arrangement of bonds around carbon atoms • recall and explain the polarity of covalent bonds

Industrial Importance • Acetone and methyl ketone are important solvents. • Formaldehyde used in polymers like Bakelite. • Flavorings and additives like vanilla, cinnamon, artificial butter. => Chapter 18 3

CARBONYL COMPOUNDS - BONDING Bonding PLANAR WITH BOND ANGLES OF 120° the carbon is sp 2 hybridised and three sigma (s) bonds are planar

CARBONYL COMPOUNDS - BONDING Bonding the carbon is sp 2 hybridised and three sigma (s) bonds are planar the unhybridised 2 p orbital of carbon is at 90° to these P ORBITAL PLANAR WITH BOND ANGLES OF 120°

CARBONYL COMPOUNDS - BONDING Bonding the carbon is sp 2 hybridised and three sigma (s) bonds are planar the unhybridised 2 p orbital of carbon is at 90° to these it overlaps with a 2 p orbital of oxygen to form a pi (p) bond P ORBITAL PLANAR WITH BOND ANGLES OF 120°

CARBONYL COMPOUNDS - BONDING Bonding the carbon is sp 2 hybridised and three sigma (s) bonds are planar the unhybridised 2 p orbital of carbon is at 90° to these it overlaps with a 2 p orbital of oxygen to form a pi (p) bond P ORBITAL PLANAR WITH BOND ANGLES OF 120° ORBITAL OVERLAP

CARBONYL COMPOUNDS - BONDING Bonding the carbon is sp 2 hybridised and three sigma (s) bonds are planar the unhybridised 2 p orbital of carbon is at 90° to these it overlaps with a 2 p orbital of oxygen to form a pi (p) bond P ORBITAL PLANAR WITH BOND ANGLES OF 120° ORBITAL OVERLAP NEW ORBITAL

CARBONYL COMPOUNDS - BONDING Bonding the carbon is sp 2 hybridised and three sigma (s) bonds are planar the unhybridised 2 p orbital of carbon is at 90° to these it overlaps with a 2 p orbital of oxygen to form a pi (p) bond P ORBITAL PLANAR WITH BOND ANGLES OF 120° ORBITAL OVERLAP NEW ORBITAL as oxygen is more electronegative than carbon the bond is polar

CARBONYL COMPOUNDS - STRUCTURE Structure carbonyl groups consists of a carbon-oxygen double bond the bond is polar due to the difference in electronegativity Difference ALDEHYDES - at least one H attached to the carbonyl group H C=O H CH 3 H C=O

CARBONYL COMPOUNDS - STRUCTURE Structure carbonyl groups consists of a carbon-oxygen double bond the bond is polar due to the difference in electronegativity Difference ALDEHYDES - at least one H attached to the carbonyl group H C=O CH 3 C=O H H KETONES - two carbons attached to the carbonyl group CH 3 C=O C 2 H 5 CH 3 C=O

Carbonyl Structure • Carbon is sp 2 hybridized. • C=O bond is shorter, stronger, and more polar than C=C bond in alkenes. => Chapter 18 12

CARBONYL COMPOUNDS - FORMULAE Molecular C 3 H 6 O Structural C 2 H 5 CHO C 2 H 5 CH 3 COCH 3 C=O H Displayed H Skeletal C=O CH 3 H H H C C C H H O O H H O H C C C H H O H

Carbonyl Compounds => Chapter 18 14

CARBONYL COMPOUNDS - NOMENCLATURE Aldehydes C 2 H 5 CHO propanal Ketones CH 3 COCH 3 propanone CH 3 CH 2 COCH 3 butanone CH 3 COCH 2 CH 3 pentan-2 -one CH 3 CH 2 COCH 2 CH 3 pentan-3 -one C 6 H 5 COCH 3 phenylethanone

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. => Chapter 18 16

Examples 3 -methyl-2 -butanone 3 -bromocyclohexanone 4 -hydroxy-3 -methyl-2 -butanone => Chapter 18 17

Naming Aldehydes • IUPAC: Replace -e with -al. • The aldehyde carbon is number 1. • If -CHO is attached to a ring, use the suffix carbaldehyde. => Chapter 18 18

Examples 3 -methylpentanal 2 -cyclopentenecarbaldehyde => Chapter 18 19

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. 3 -methyl-4 -oxopentanal 3 -formylbenzoic acid Chapter 18 => 20

Common Names for Ketones • Named as alkyl attachments to -C=O. • Use Greek letters instead of numbers. methyl isopropyl ketone a-bromoethyl isopropyl ketone => Chapter 18 21

Historical Common Names acetophenone acetone benzophenone => Chapter 18 22

Aldehyde Common Names • Use the common name of the acid. • Drop -ic acid and add -aldehyde. – 1 C: formic acid, formaldehyde – 2 C’s: acetic acid, acetaldehyde – 3 C’s: propionic acid, propionaldehyde – 4 C’s: butyric acid, butyraldehyde. => Chapter 18 23

CARBONYL COMPOUNDS - FORMATION ALDEHYDES Oxidation of primary (1°) alcohols RCH 2 OH + [O] ——> RCHO + H 2 O beware of further oxidation RCHO + [O] ——> RCOOH Reduction of carboxylic acids RCOOH + [H] ——> RCHO + H 2 O KETONES Oxidation of secondary (2°) alcohols RCHOHR + [O] ——> RCOR + H 2 O

CARBONYL COMPOUNDS - IDENTIFICATION Method 1 strong peak around 1400 -1600 cm-1 in the infra red spectrum Method 2 formation of an orange precipitate with 2, 4 -dinitrophenylhydrazine Although these methods identify a carbonyl group, they cannot tell the difference between an aldehyde or a ketone. To narrow it down you must do a second test.

CARBONYL COMPOUNDS - IDENTIFICATION Differentiation Tollen’s Reagent to distinguish aldehydes from ketones, use a mild oxidising agent ammoniacal silver nitrate mild oxidising agent which will oxidise aldehydes but not ketones contains the diammine silver(I) ion - [Ag(NH 3)2 ]+ the silver(I) ion is reduced to silver Ag+(aq) + e¯ ——> Ag(s) the test is known as THE SILVER MIRROR TEST

Tollens Test • Add ammonia solution to Ag. NO 3 solution until precipitate dissolves. • Aldehyde reaction forms a silver mirror. => Chapter 18 27

Boiling Points • More polar, so higher boiling point than comparable alkane or ether. • Cannot H-bond to each other, so lower boiling point than comparable alcohol. => Chapter 18 28

Solubility • Good solvent for alcohols. • Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O-H or N-H. • Acetone and acetaldehyde are miscible in water. => Chapter 18 29

Formaldehyde • Gas at room temperature. • Formalin is a 40% aqueous solution. formaldehyde, b. p. -21 C trioxane, m. p. 62 C formalin => Chapter 18 30

CARBONYL COMPOUNDS - IDENTIFICATION Differentiation Tollen’s Reagent Fehling’s Solution to distinguish aldehydes from ketones, use a mild oxidising agent ammoniacal silver nitrate mild oxidising agent which will oxidise aldehydes but not ketones contains the diammine silver(I) ion - [Ag(NH 3)2 ]+ the silver(I) ion is reduced to silver Ag+(aq) + e¯ ——> Ag(s) the test is known as THE SILVER MIRROR TEST contains a copper(II) complex ion giving a blue solution on warming, it will oxidise aliphatic (but not aromatic) aldehydes the copper(II) is reduced to copper(I) a red precipitate of copper(I) oxide, Cu 2 O, is formed The silver mirror test is the better alternative as it works with all aldehydes Ketones do not react with Tollen’s Reagent or Fehling’s Solution

CARBONYL COMPOUNDS - CHEMICAL PROPERTIES OXIDATION • • provides a way of differentiating between aldehydes and ketones mild oxidising agents are best aldehydes are easier to oxidise powerful oxidising agents oxidise ketones to a mixture of carboxylic acids ALDEHYDES easily oxidised to acids RCHO(l) + [O] ——> RCOOH(l) CH 3 CHO(l) + [O] ——> CH 3 COOH(l) KETONES oxidised under vigorous conditions to acids with fewer carbons C 2 H 5 COCH 2 CH 3(l) + 3 [O] ——> C 2 H 5 COOH(l) + CH 3 COOH(l)

Oxidation of Aldehydes Easily oxidized to carboxylic acids. => Chapter 18 33

CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION Reagent hydrogen cyanide - HCN (in the presence of KCN) Conditions reflux in alkaline solution Nucleophile cyanide ion CN¯ Product(s) hydroxynitrile (cyanohydrin) Equation CH 3 CHO Notes HCN is a weak acid and has difficulty dissociating into ions + HCN ——> CH 3 CH(OH)CN 2 -hydroxypropanenitrile H+ + CN¯ the reaction is catalysed by alkali which helps produce more of the nucleophilic CN¯

CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION Mechanism occurs with both aldehydes and ketones involves addition to the C=O double bond unlike alkenes, they are attacked by nucleophiles attack is at the positive carbon centre due to the difference in electronegativities alkenes are non-polar and are attacked by electrophiles undergoing electrophilic addition Group Bond Polarity Attacking species Result ALKENES C=C NON-POLAR ELECTROPHILES ADDITION CARBONYLS C=O POLAR NUCLEOPHILES ADDITION

CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION Mechanism Nucleophilic addition STEP 1 Step 1 CN¯ acts as a nucleophile and attacks the slightly positive C One of the C=O bonds breaks; a pair of electrons goes onto the O

CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION Mechanism Nucleophilic addition STEP 1 STEP 2 Step 1 CN¯ acts as a nucleophile and attacks the slightly positive C One of the C=O bonds breaks; a pair of electrons goes onto the O Step 2 A pair of electrons is used to form a bond with H+ Overall, there has been addition of HCN

CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION ANIMATED MECHANISM

CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION Watch out for the possibility of optical isomerism in hydroxynitriles CN¯ attacks from above CN¯ attacks from below

CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION ANIMATED MECHANISM

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. Chapter 18 44 =>

Wittig Reaction • Nucleophilic addition of phosphorus ylides. • Product is alkene. C=O becomes C=C. Chapter 18 45 =>

Phosphorus Ylides • Prepared from triphenylphosphine and an unhindered alkyl halide. • Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus. ylide Chapter 18 => 46

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. Chapter 18 => 47

Addition of Water • In acid, water is the nucleophile. • In base, hydroxide is the nucleophile. • Aldehydes are more electrophilic since they have fewer e--donating alkyl groups. => Chapter 18 48

Addition of HCN • HCN is highly toxic. • Use Na. CN or KCN in base to add cyanide, then protonate to add H. • Reactivity formaldehyde > aldehydes > ketones >> bulky ketones. Chapter 18 49 =>

Formation of Imines • Nucleophilic addition of ammonia or primary amine, followed by elimination of water molecule. • C=O becomes C=N-R Chapter 18 =>50

p. H Dependence • Loss of water is acid catalyzed, but acid destroys nucleophiles. • NH 3 + H+ NH 4+ (not nucleophilic) • Optimum p. H is around 4. 5 => Chapter 18 51

Other Condensations Chapter 18 52 =>

Addition of Alcohol => Chapter 18 53

CARBONYL COMPOUNDS - REDUCTION WITH Na. BH 4 Reagent sodium tetrahydridoborate(III) (sodium borohydride), Na. BH 4 Conditions aqueous or alcoholic solution Mechanism Nucleophilic addition (also reduction as it is addition of H¯) Nucleophile H¯ (hydride ion) Product(s) Alcohols Aldehydes are REDUCED to primary (1°) alcohols. Ketones are REDUCED to secondary (2°) alcohols. Equation(s) CH 3 CHO + 2[H] CH 3 COCH 3 + 2[H] Notes The water provides a proton Question Na. BH 4 doesn’t reduce C=C bonds. WHY? CH 2 = CHCHO + ——> 2[H] CH 3 CH 2 OH CH 3 CHOHCH 3 ———> CH 2 = CHCH 2 OH

CARBONYL COMPOUNDS - REDUCTION WITH HYDROGEN Reagent hydrogen Conditions catalyst - nickel or platinum Reaction type Hydrogenation, reduction Product(s) Alcohols Aldehydes are REDUCED to primary (1°) alcohols. Ketones are REDUCED to secondary (2°) alcohols. Equation(s) CH 3 CHO + H 2 CH 3 COCH 3 + H 2 Note ——> CH 3 CH 2 OH ——> CH 3 CHOHCH 3 Hydrogen also reduces C=C bonds CH 2 = CHCHO + 2 H 2 ——> CH 3 CH 2 OH

CARBONYL COMPOUNDS - REDUCTION Introduction Functional groups containing multiple bonds can be reduced C=C C=O C N Hydrogen Reactions is reduced to CH-CH CH-OH CH-NH 2 H • H 2 H+ (electrophile) H¯ (nucleophile) Hydrogen reduces C=C and C=O bonds CH 2 = CHCHO + 4[H] ——> CH 3 CH 2 OH Hydride ion H¯ reduces C=O bonds CH 2 = CHCHO + 2[H] ——> CH 2=CHCH 2 OH Explanation C=O is polar so is attacked by the nucleophilic H¯ C=C is non-polar so is not attacked by the nucleophilic H¯

CARBONYL COMPOUNDS - REDUCTION Example COMPOUND X What are the products when Compound X is reduced? H 2 Na. BH 4

CARBONYL COMPOUNDS - REDUCTION Example What are the products when Compound X is reduced? COMPOUND X H 2 Na. BH 4 C=O is polar so is attacked by the nucleophilic H¯ C=C is non-polar so is not attacked by the nucleophilic H¯

Reduction Reagents • Sodium borohydride, Na. BH 4, reduces C=O, but not C=C. • Lithium aluminum hydride, Li. Al. H 4, much stronger, difficult to handle. • Hydrogen gas with catalyst also reduces the C=C bond. => Chapter 18 59

Catalytic Hydrogenation • Widely used in industry. • Raney nickel, finely divided Ni powder saturated with hydrogen gas. • Pt and Rh also used as catalysts. => Chapter 18 60

Deoxygenation • Reduction of C=O to CH 2 • Two methods: – Clemmensen reduction if molecule is stable in hot acid. – Wolff-Kishner reduction if molecule is stable in very strong base. => Chapter 18 61

Clemmensen Reduction => Chapter 18 62

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. => Chapter 18 63

2, 4 -DINITROPHENYLHYDRAZINE Structure C 6 H 3(NO 2)2 NHNH 2 Use reacts with carbonyl compounds (aldehydes and ketones) used as a simple test for aldehydes and ketones makes orange crystalline derivatives - 2, 4 -dinitrophenylhydrazones derivatives have sharp, well-defined melting points also used to characterise (identify) carbonyl compounds. Identification / characterisation A simple way of characterising a compound (finding out what it is) is to measure the melting point of a solid or the boiling point of a liquid.

2, 4 -DINITROPHENYLHYDRAZINE C 6 H 3(NO 2)2 NHNH 2 The following structural isomers have similar boiling points because of similar van der Waals forces and dipole-dipole interactions. They would be impossible to identify with any precision using boiling point determination. CHO CHO Cl Cl Cl Boiling point 213°C 214°C Melting point of 2, 4 -dnph derivative 209°C 248°C 265°C By forming the 2, 4 -dinitrophenylhydrazone derivative and taking its melting point, it will be easier to identify the unknown original carbonyl compound.

Synthesis Review • Oxidation – 2 alcohol + Na 2 Cr 2 O 7 ketone – 1 alcohol + PCC aldehyde • Ozonolysis of alkenes. => Chapter 18 66

Synthesis Review (2) • Friedel-Crafts acylation – Acid chloride/Al. Cl 3 + benzene ketone – CO + HCl + Al. Cl 3/Cu. Cl + benzene benzaldehyde (Gatterman-Koch) • Hydration of terminal alkyne – Use Hg. SO 4, H 2 O for methyl ketone – Use Sia 2 BH followed by H 2 O 2 in Na. OH for aldehyde. => Chapter 18 67

Synthesis Using 1, 3 -Dithiane • Remove H+ with n-butyllithium. • Alkylate with primary alkyl halide, then hydrolyze. => Chapter 18 68

Ketones from 1, 3 -Dithiane • After the first alkylation, remove the second H+, react with another primary alkyl halide, then hydrolyze. => Chapter 18 69

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. => Chapter 18 70

Ketones from Nitriles • A Grignard or organolithium reagent attacks the nitrile carbon. • The imine salt is then hydrolyzed to form a ketone. => Chapter 18 71

Aldehydes from Acid Chlorides Use a mild reducing agent to prevent reduction to primary alcohol. => Chapter 18 72

Ketones from Acid Chlorides Use lithium dialkylcuprate (R 2 Cu. Li), formed by the reaction of 2 moles of R-Li with cuprous iodide. => Chapter 18 73

Mechanism • Must be acid-catalyzed. • Adding H+ to carbonyl makes it more reactive with weak nucleophile, ROH. • Hemiacetal forms first, then acid-catalyzed loss of water, then addition of second molecule of ROH forms acetal. • All steps are reversible. => Chapter 18 74

Mechanism for Hemiacetal Chapter 18 75 =>

Hemiacetal to Acetal => Chapter 18 76

Cyclic Acetals • Addition of a diol produces a cyclic acetal. • Sugars commonly exist as acetals or hemiacetals. => Chapter 18 77

Acetals as Protecting Groups • Hydrolyze easily in acid, stable in base. • Aldehydes more reactive than ketones. => Chapter 18 78

Selective Reaction of Ketone • React with strong nucleophile (base) • Remove protective group. => Chapter 18 79

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