Functional Group Interconversions in Organic Chemistry

Functional Group Interconversions

Electrophiles and Nucleophiles

Electrophiles O 8- Carboxylic acid R &+ OH O 8- Aldehyde R &+ H O 8- Ketone R' S+ R' 8 − O 8- R 8+ X Acyl halide X = Cl, Br, I · Carbon-oxygen bond is polarised (have a dipole) · electronegative oxygen · carbon has slight positive charge . attacked by nucleophiles, i.e., those with electron-rich functional groups (e.g., lone-pair) . they are electrophiles O Amide R' R N R" (Generally unreactive)Join: vevox.app ID: 154-321-945 POLL OPEN Do you know what is meant by the term nucleophile? 1. Yes 73.91% 2. No 8.7% 3. Possibly 17.39%

Nucleophiles and Functional Groups

Nucleophiles R-NH 2 Primary Amine .. Secondary Amine R N"H R' R-OH Alcohol . . Thiol / Mercaptan R-SH . . . . R-O-R' .. Ether (unreactive) . C - heteroatom bond only partially polarised · Electron lone pairs remain on heteroatom . These are nucleophiles, i.e., react with electron-deficient functional groups Please familiarise yourselves with structural differences between primary, secondary and tertiary alcohols and amines. Q: What is a quaternary amine?Join: vevox.app ID: 154-321-945 POLL OPEN What type of amine is NHMe ?? 1. Primary 13.51% 2. Secondary 64.86% 3. Tertiary 18.92% 4. Quaternary 2.7%

Functional Group Interconversions

Curly Arrows in Reactions

"Curly Arrows" X 8+ N. 8- H H Nucleophile (attacks an electron- deficient centre) - O + R N-H R' H 1 Type of reaction: Nucleophilic Substitution H N-R' O R + HX H H / N-R' + O R X O R

Functional Group Interconversions

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution (EAS): Bromination .. – : Br-Br : + FeBr3 Br-Br± Fe Br3 .. – + Br-Br- Fe Br3 Br H B + HB+ Ferric bromide (FeBr3) is a Lewis acid catalyst - accepts an electron pair B is a base Br

EAS Nitration Process

EAS Nitration HNO3 + 2H2SO4 H3O+ + 2HSO- + NO2+ O + + NO2 NO2 H B + HB+ . NO2+ is a nitronium ion and is the electrophile · B is any base (e.g., HSO4, H2O, solvent) that can remove H+ Remember: Electrophile - species that is attracted to electrons, e.g., NO2+ Nucleophile - species that donates electrons, e.g., NH3 [lone-pair]

EAS Sulfonation Mechanism

EAS Sulfonation SO3H 3 c. H2SO4 +SO3H sulfonium ion is the actual electrophile Please familiarise yourselves with the mechanisms of this reaction. Clue: Compare to EAS Nitration reactionJoin: vevox.app ID: 154-321-945 POLL OPEN Do you remember the Friedel crafts reactions? 1. Yes 13.64% 2. Yes from last year 0% 3. Yes from A-level 54.55% 4. Not sure 4.55% 5. No 27.27%

Friedel-Crafts Alkylation Reaction

Friedel-Crafts Alkylation R-CI : + AlCl3 - R+ + AICI 4 . . + + R H B R + HB+ · Carbocation R+ is the electrophile · AICI3 is a catalyst • B is a base

Friedel-Crafts Acylation Reaction

Friedel-Crafts Acylation + R O + AICI4 R CI : O O + + R O R R H B + HB+ + · R-C=O is an acylium ion and is the electrophile · R-C=O is an acyl group . AICI3 is a catalyst · B is a base + AlCl3

Functional Group Interconversions

Reactions of Alcohols

Functional Group Inter-conversions (FGIs) R1 O Carboxylic acid OH O R2 OH KMnO 4 + H R1 O H PCC OH Alcohol Na on dried alcohol PX3 or HX direct R1 X Halogenoalkane R1 o- Na + Alkoxide R2-X R1 0-R2 Ether Alkene R2 O -R1 KMno / H+ 4 Ester / H+ R1 Aldehyde H2SO4 / heat R1Join: vevox.app ID: 154-321-945 POLL OPEN PhCH2OCH2CH3 is ... 1. An ester 11.54% 2. An ether 53.85% 3. A carboxylic acid 3.85% 4. An alcohol 0% 5. An ketone 30.77%Join: vevox.app ID: 154-321-945 POLL OPEN In the reaction of alcohols with conc. sulfuric acid, the acid behaves as: 1. An oxidising agent producing an aldehyde 16.13% 2. A dehydrating agent producing an ether 0% 3. A catalyst to produce an ester 12.9% 4. A dehydrating agent producing an alkene 64.52% 5. An oxidising agent producing a ketone 6.45%

Functional Group Interconversions Diagram

FGIs PEG / PAG Amine Acyl halide Base / ROH Amide Heat / H+ PCI3 / PCI5 or SOCI2 H2 /Pd/C Epoxide CO2 Alkyl aromatic compound Diol K2Cr207 / H+ NaH Heat / 02 NaBH4 m-CBPA KMn04 Carboxylic acid Halohydrin H+ /H20 Br2 / H20 Alkene H2SO4 / H20 KMn04 H2 / Nik or Pd Hg(OAc)2 / H20 / NaBH4 LiAIH4 LiAIH4 Alkane BH3 / THF or NaOH / H202 2º POCI3 / py 3º 1° cH2SO4 ......... Carboxylic acid / H+ Alcohol PPh3 / Carbonyl compound X2 or HX Imine OH- alcoholic ROH / H+ LiAIH4 Amine X2 / hv OH- aq Na Mg / CO2 Amine HX LiAIH4 Alkoxide Mg / Carbonyl compound Halogenoalkane NH3 Nitrile Disulfide 12 NaCN Ether Thiol Halogenoalkane Thioether Base / RX NaSH or H2S NaBH4 / base H20/base Acyl halide LiAIH4 ........... PCC RMgX Ester PCI3 Ketone / Aldehyde AICI3 / Aromatic compound

Functional Group Interconversions

Oxidation by PCC

Oxidation Reactions: PCC O II – CI-Cr-O II + + + N H · Pyridinium Chlorochromate (PCC) · A milder version of chromic acid. . It oxidises alcohols one rung up the oxidation ladder: · From primary alcohols to aldehydes · From secondary alcohols to ketones · Tertiary alcohols do not oxidise even with KMnO4 / H+

PCC Oxidation Example

Oxidation Reactions: PCC Example エ - O PCC + + OH O Cr + HO OH N CI- H Cyclohexylmethanol Cyclohexanecarboxaldehyde Cr(IV)Join: vevox.app ID: 154-321-945 POLL OPEN PhCH OH + KOH -> ? 1. PhCH KOH + OH- 9.38% 2. PhCH OCH2Ph + H2 + K+ 3.13% 3. PhCH OK + H2O 68.75% 4. PhCH,O- Na+ + H2O 9.38% 5. CH3CH2OK + H2O 9.38%Join: vevox.app ID: 154-321-945 POLL OPEN PhCH O + EtBr -> ? 1. PhCHOEt + Br 41.38% 2. PhCH_Br + EtOH 31.03% 3. PhCH,Et + OBr 20.69% 4. PhCO2H + MeBr 0% 5. PhCH OBr + CH3CH3 6.9%Join: vevox.app ID: 154-321-945 POLL OPEN Ph(CH ) OH + PCC -> ? 1. Ph(CH2)3CO2H 4% 2. Ph(CH2)2CH=CH2 8% 3. Ph(CH2)3PCC 0% 4. Ph(CH2)3CHO 56% 5. Ph(CH ) CHO 32%Join: vevox.app ID: 154-321-945 POLL OPEN CH3 CH2CO2H + PhCH OH -> ? 1. CH3CH2CO2CH2Ph 30.43% 2. PhCH CO2CH2CH3 13.04% 3. CH3CO2CH2Ph 8.7% 4. CH3 CH2COCH2Ph 5. PhCH CO2CH2Ph 0% 47.83%Join: vevox.app ID: 154-321-945 POLL OPEN X + Y -> CH3OCH3 1. X = CH3CO Na+ Y = CH3 I 10% 2. X = CH3O- K+ Y = CH3Br 3. X = CH3 CO2H Y = CH3Cl 4. X = CH3CO Na+ Y = CH3OH 20% X = CH3O Na+ Y = CH3OH 40% 0% 30%Join: vevox.app ID: 154-321-945 POLL OPEN MeOH + PCI3 -> ? (ignore side-product) 1. MeCl 2. MeCl2 3. MeCl3 4. MePCl3 5. MeOCl