Chapter 9 - Amines

Beginner

Topper

1. Introduction - What is Amine? Smell of Fish

Open a fish market you smell strong fishy smell - that is trimethylamine (CH3)3N. Onion garlic smell also amines. Amines are derivatives of ammonia NH3 where one or more H replaced by alkyl or aryl groups.

Primary amine R-NH2 one alkyl replaces one H example methylamine CH3NH2 gas fishy smell, ethylamine CH3CH2NH2. Secondary R2-NH two alkyls replace two H example dimethylamine (CH3)2NH. Tertiary R3-N three alkyls replace three H example trimethylamine (CH3)3N fishy. Quaternary ammonium salt R4N+ X- four alkyls all H replaced positive charge example tetraethylammonium bromide (C2H5)4N+ Br- used as phase transfer catalyst.

Aromatic amine aniline C6H5NH2 benzene ring with NH2 directly attached important for dyes drugs. Toluidine methyl aniline CH3C6H4NH2 three isomers o m p.

Amines NH3 derivatives H replaced by alkyl aryl | Primary R-NH2 one alkyl methylamine CH3NH2 fishy ethylamine | Secondary R2-NH two alkyl dimethylamine (CH3)2NH | Tertiary R3-N three alkyl trimethylamine (CH3)3N fish market fishy onion garlic | Quaternary R4N+ X- four alkyl positive tetraethylammonium bromide phase transfer | Aromatic aniline C6H5NH2 benzene+NH2 dyes drugs toluidine CH3C6H4NH2 o m p isomers

Visual Learning Method: Fish market trimethylamine fishy smell, ammonia NH3 to R-NH2 primary methylamine, R2-NH secondary dimethylamine, R3-N tertiary trimethylamine, R4N+ quaternary positive, aniline C6H5NH2 benzene+NH2 toluidine methyl aniline.

Daily Analogy: Amines like ammonia family replacing children. Primary one child alkyl, secondary two children, tertiary three children crowded fishy smell, quaternary four children no H left positive charge.

Introduction - What is Amine?

Revision Points - Easy:

Amines NH3 derivatives H replaced by alkyl aryl.
Primary R-NH2 one alkyl methylamine fishy, secondary R2-NH two alkyl dimethylamine, tertiary R3-N three alkyl trimethylamine fish market.
Quaternary R4N+ X- four alkyl positive charge phase transfer catalyst.
Aromatic aniline C6H5NH2 benzene+NH2 dyes drugs toluidine methyl aniline.

2. Nomenclature & Structure - Naming and Shape

IUPAC simple amines named as alkanamine methanamine CH3NH2 methylamine, ethanamine CH3CH2NH2 ethylamine, N-methylmethanamine CH3NHCH3 dimethylamine N shows alkyl on nitrogen, N,N-dimethylmethanamine (CH3)3N trimethylamine, benzenamine C6H5NH2 aniline common name used.

Structure nitrogen sp3 pyramidal shape like ammonia umbrella with lone pair at top bond angle ~107 degrees less than tetrahedral 109.5 due to lone pair repulsion pushes bonds closer. Chirality possible if four different groups on N? But amines invert quickly like umbrella flips so not optically active generally rapid inversion.

H-bonding: primary secondary have N-H can H-bond between themselves N-H...N hydrogen bonding so boiling point higher than tertiary which has no N-H cannot H-bond between themselves. Example ethylamine CH3CH2NH2 boiling 16.6 C vs dimethylamine (CH3)2NH 7.4 C vs trimethylamine (CH3)3N 2.8 C similar mass primary higher due to more H-bonding. All amines can H-bond with water N can accept H from water O-H...N and N-H donate to water O so small amines soluble in water methanol amine methylamine fully soluble larger chain solubility decreases non-polar dominates. Smell fishy.

IUPAC alkanamine methanamine CH3NH2 methylamine ethanamine CH3CH2NH2 ethylamine N-methylmethanamine CH3NHCH3 dimethylamine N,N-dimethylmethanamine (CH3)3N trimethylamine benzenamine C6H5NH2 aniline | Structure sp3 pyramidal umbrella lone pair top angle ~107 lone pair repulsion pushes bonds chirality four different rapid inversion umbrella flips not optically active generally | H-bonding primary secondary N-H H-bond N-H...N higher boiling than tertiary no N-H ethylamine 16.6 dimethylamine 7.4 trimethylamine 2.8 similar mass primary higher more H-bonding All H-bond with water N accepts H from water O-H...N N-H donates to water O small soluble water methylamine fully soluble larger decreases non-polar dominates fishy smell

Visual Learning Method: IUPAC methanamine ethanamine N-methyl N,N-dimethyl benzenamine aniline, structure pyramidal umbrella lone pair top angle 107, inversion umbrella flip, H-bonding N-H...N primary higher boiling ethylamine 16.6 dimethylamine 7.4 trimethylamine 2.8, H-bond with water soluble methylamine fully larger less soluble fishy.

Daily Analogy: Pyramidal shape like umbrella lone pair top pushing ribs bonds closer 107 degrees. Inversion like umbrella flips inside out quickly so chirality not stable. H-bonding like holding hands primary has two hands N-H can hold another amine higher boiling tertiary no hands no holding lower boiling.

Nomenclature & Structure

Revision Points - Easy:

IUPAC alkanamine methanamine methylamine ethanamine ethylamine N-methylmethanamine dimethylamine N,N-dimethylmethanamine trimethylamine benzenamine aniline.
Structure sp3 pyramidal umbrella lone pair top angle ~107 lone pair repulsion rapid inversion umbrella flips not optically active.
H-bonding primary secondary N-H H-bond between themselves higher boiling than tertiary no N-H ethylamine 16.6 dimethylamine 7.4 trimethylamine 2.8.
All H-bond with water soluble small methylamine fully soluble larger less soluble fishy smell.

3. Preparation of Amines - Making Amines from Scratch

From nitro compounds: reduction nitro R-NO2 + Sn HCl or Fe HCl or H2 Pd gives amine R-NH2. Example nitrobenzene C6H5NO2 + Sn HCl -> aniline C6H5NH2 + SnCl4 + H2O. Industrial H2 Ni. Most common for aniline.

From haloalkanes: R-X + NH3 excess -> R-NH2 + HX but over alkylation gives mixture primary secondary tertiary quaternary mixture not pure because R-NH2 more nucleophilic than NH3 further reacts with RX gives secondary R2NH etc. So not good for pure primary need excess NH3 to minimize but still mixture.

From nitriles: RCN + LiAlH4 reduction or H2 Ni gives primary amine RCH2NH2 adds one carbon more than alkyl halide. Example CH3CN acetonitrile + LiAlH4 -> CH3CH2NH2 ethylamine adds CH2.

From amides: RCONH2 + LiAlH4 reduction gives RCH2NH2 primary amine same carbon count amide to amine. Hofmann bromamide reaction: amide RCONH2 + Br2 NaOH gives R-NH2 primary amine with one carbon less removes carbonyl CO as carbonate. Example acetamide CH3CONH2 + Br2 NaOH -> CH3NH2 methylamine one carbon less than acetamide. Very important to reduce carbon count. Reaction: RCONH2 + Br2 +4NaOH -> R-NH2 + Na2CO3 +2NaBr+2H2O.

Gabriel phthalimide synthesis: pure primary amine preparation avoids mixture. Phthalimide + KOH -> potassium phthalimide + RX alkyl halide -> N-alkyl phthalimide then NaOH hydrolysis -> R-NH2 primary + phthalic acid pure primary no secondary tertiary. Used for primary only.

Daily: aniline from nitrobenzene lab preparation.

Nitro reduction R-NO2+Sn HCl Fe HCl H2 Pd R-NH2 nitrobenzene C6H5NO2 Sn HCl aniline C6H5NH2 SnCl4 H2O industrial H2 Ni most common aniline | Haloalkanes R-X+NH3 excess R-NH2+HX over alkylation mixture primary secondary tertiary quaternary not pure R-NH2 more nucleophilic than NH3 further RX secondary R2NH etc excess NH3 minimize but mixture not good pure primary | Nitriles RCN+LiAlH4 or H2 Ni primary RCH2NH2 adds one C more than alkyl halide CH3CN+LiAlH4 CH3CH2NH2 ethylamine adds CH2 | Amides RCONH2+LiAlH4 RCH2NH2 primary same C count amide to amine Hofmann bromamide RCONH2+Br2 NaOH R-NH2 one C less removes CO as carbonate CH3CONH2+Br2 NaOH CH3NH2 methylamine one C less acetamide to methylamine Reaction RCONH2+Br2+4NaOH R-NH2+Na2CO3+2NaBr+2H2O | Gabriel phthalimide synthesis pure primary avoids mixture phthalimide+KOH potassium phthalimide+RX N-alkyl phthalimide NaOH hydrolysis R-NH2 primary+phthalic acid pure primary no secondary tertiary primary only

Visual Learning Method: Nitro reduction nitrobenzene Sn HCl aniline, haloalkanes NH3 mixture over alkylation primary secondary tertiary quaternary not pure, nitriles RCN LiAlH4 primary RCH2NH2 adds one C CH3CN ethylamine, amides LiAlH4 RCH2NH2 same C Hofmann bromamide RCONH2 Br2 NaOH R-NH2 one C less acetamide methylamine, Gabriel phthalimide pure primary no mixture.

Daily Analogy: Haloalkane NH3 gives mixture like party overcrowding primary brings friends secondary tertiary. Gabriel pure primary like VIP entry only one guest allowed no overcrowding. Hofmann bromamide cuts one carbon like trimming tail one carbon less.

Preparation of Amines

Revision Points - Easy:

Nitro reduction R-NO2 Sn HCl Fe HCl H2 Pd R-NH2 nitrobenzene to aniline most common.
Haloalkanes R-X+NH3 mixture primary secondary tertiary quaternary not pure over alkylation excess NH3 minimize but mixture.
Nitriles RCN LiAlH4 H2 Ni primary RCH2NH2 adds one C CH3CN to ethylamine.
Amides RCONH2 LiAlH4 RCH2NH2 same C Hofmann bromamide RCONH2 Br2 NaOH R-NH2 one C less removes CO acetamide to methylamine.
Gabriel phthalimide synthesis pure primary avoids mixture primary only.

4. Physical Properties & Basicity - Why Amines are Basic?

Amines basic because nitrogen has lone pair can donate to acid H+ forms NH4+ alkylammonium RNH3+ Lewis base. Stronger base means more available lone pair.

Factors affecting basicity: alkyl groups +I electron donating inductive effect pushes electrons to N increases electron density lone pair more available stronger base. So tertiary should be most basic? But in water solvation also matters H-bonding stabilizes ammonium ion more H on N more solvation more stable more basic. So order in gas phase: tertiary greater than secondary greater than primary greater than ammonia NH3 because +I dominates. In aqueous water solvation + steric +I combined order secondary greater than primary greater than tertiary greater than ammonia for methyl amines (CH3)2NH secondary most basic due to balance +I and solvation. For ethyl amines secondary greater than tertiary greater than primary greater than ammonia (C2H5)2NH most basic. Aniline C6H5NH2 very weak base much weaker than aliphatic because lone pair delocalized into benzene ring resonance 5 structures negative on ring delocalized reduces availability for donation pKb aniline 9.37 vs methylamine 3.38 larger pKb weaker base. Electron withdrawing NO2 at o p decreases basicity more NO2 withdraws resonance -I -M, electron donating CH3 OCH3 at o p increases basicity. p-NO2 aniline very weak almost non-basic, p-CH3 aniline slightly more basic than aniline.

Boiling higher than alkanes similar mass due to H-bonding primary secondary can H-bond N-H...N, tertiary no N-H no H-bond between themselves lower boiling than primary secondary as earlier.

Basic because N lone pair donates H+ forms NH4+ RNH3+ Lewis base stronger base more available lone pair | Factors alkyl +I electron donating pushes electrons to N increases electron density stronger base gas phase tertiary>secondary>primary>ammonia +I dominates aqueous water solvation H-bonding stabilizes ammonium more H on N more solvation more stable more basic balance order aqueous methyl amines (CH3)2NH secondary most basic secondary>primary>tertiary>ammonia ethyl amines secondary>tertiary>primary>ammonia (C2H5)2NH most basic | Aniline C6H5NH2 very weak base weaker than aliphatic lone pair delocalized benzene resonance 5 structures negative on ring reduces availability pKb aniline 9.37 methylamine 3.38 larger pKb weaker | EW NO2 o p decreases basicity NO2 withdraws resonance -I -M p-NO2 aniline very weak non-basic ED CH3 OCH3 o p increases basicity p-CH3 aniline slightly more basic than aniline | Boiling higher than alkanes H-bonding primary secondary N-H...N tertiary no N-H no H-bond between themselves lower boiling than primary secondary

Visual Learning Method: Basic N lone pair donates H+ NH4+ RNH3+, alkyl +I increases basicity gas tertiary greater than secondary greater than primary greater than ammonia, aqueous secondary most basic (CH3)2NH secondary greater than primary greater than tertiary greater than ammonia due to solvation, aniline weak base lone pair delocalized resonance 5 structures pKb 9.37 vs methylamine 3.38, EW NO2 decreases basicity p-NO2 very weak ED CH3 increases p-CH3 more basic, boiling primary higher than tertiary N-H...N H-bonding.

Daily Analogy: Basicity like generosity lone pair donation. Alkyl groups donate money +I makes person generous more basic. Aniline lone pair busy in benzene ring resonance like person busy in meeting less available for donation weaker base. NO2 withdraws money makes poor less basic. Solvation like friends support ammonium more H more friends H-bonding support more stable more basic aqueous.

Physical Properties & Basicity

Revision Points - Easy:

Basic because N lone pair donates H+ forms NH4+ RNH3+ Lewis base.
Alkyl +I increases basicity gas tertiary greater than secondary greater than primary greater than ammonia.
Aqueous methyl amines secondary greater than primary greater than tertiary greater than ammonia secondary (CH3)2NH most basic ethyl secondary greater than tertiary greater than primary greater than ammonia.
Aniline very weak base lone pair delocalized benzene resonance pKb 9.37 vs methylamine 3.38 larger pKb weaker base.
EW NO2 o p decreases basicity p-NO2 very weak ED CH3 OCH3 increases basicity p-CH3 more basic than aniline.
Boiling higher than alkanes H-bonding primary secondary N-H...N tertiary no N-H no H-bond between themselves lower boiling than primary secondary.

5. Chemical Reactions - How Amines React

Alkylation: amine R-NH2 + alkyl halide RX -> secondary amine R2NH + HX further alkylation gives tertiary R3N and quaternary R4N+ X- mixture over alkylation. Example CH3NH2 + CH3CH2Br -> CH3NHCH2CH3 N-ethylmethylamine secondary.

Acylation: R-NH2 + acid chloride CH3COCl acetyl chloride or anhydride (CH3CO)2O acetic anhydride -> amide R-NHCOCH3 + HCl. Example aniline C6H5NH2 + CH3COCl -> C6H5NHCOCH3 acetanilide amide protects NH2 for further electrophilic substitution to avoid oxidation and controls o p to para mainly. Acylation reduces basicity because lone pair delocalized to carbonyl.

Carbylamine test: primary amine R-NH2 + CHCl3 chloroform + 3 KOH alcoholic heat -> R-NC isocyanide isocyanide R-NC foul extremely bad smell +3 KCl+3H2O. Test for primary amines only primary gives foul smell secondary tertiary no. Example CH3NH2 + CHCl3 +3KOH -> CH3NC methyl isocyanide foul smell. Distinguishes primary from secondary tertiary. Very sensitive test.

Reaction with HNO2 nitrous acid distinguishes primary secondary tertiary. Primary aliphatic R-NH2 + HNO2 NaNO2 HCl cold -> R-OH alcohol + N2 gas bubbles + H2O N2 evolution observed bubbles brisk effervescence. Example CH3CH2NH2 + HNO2 -> CH3CH2OH + N2 bubbles. Secondary R2NH + HNO2 -> R2N-N=O nitrosamine yellow oily layer carcinogenic N-nitrosamine. Tertiary R3N + HNO2 -> no reaction solution unchanged no gas no oil. So test to distinguish.

Daily: carbylamine foul smell like rotten cabbage used to test primary amine lab.

Alkylation R-NH2+RX R2NH+HX further R3N R4N+ X- mixture over alkylation CH3NH2+CH3CH2Br CH3NHCH2CH3 N-ethylmethylamine secondary | Acylation R-NH2+CH3COCl acetyl chloride or (CH3CO)2O anhydride amide R-NHCOCH3+HCl aniline C6H5NH2+CH3COCl C6H5NHCOCH3 acetanilide protects NH2 further electrophilic substitution avoids oxidation controls o p to para mainly reduces basicity lone pair delocalized carbonyl | Carbylamine primary R-NH2+CHCl3+3KOH alcoholic heat R-NC isocyanide foul extremely bad smell+3KCl+3H2O test primary only primary foul secondary tertiary no CH3NH2+CHCl3+3KOH CH3NC methyl isocyanide foul distinguishes primary secondary tertiary sensitive test | HNO2 nitrous acid distinguishes primary secondary tertiary Primary aliphatic R-NH2+HNO2 NaNO2 HCl cold R-OH+N2 gas bubbles+H2O N2 evolution bubbles brisk effervescence CH3CH2NH2+HNO2 CH3CH2OH+N2 bubbles Secondary R2NH+HNO2 R2N-N=O nitrosamine yellow oily layer carcinogenic N-nitrosamine Tertiary R3N+HNO2 no reaction solution unchanged no gas no oil test distinguishes

Visual Learning Method: Alkylation R-NH2+RX R2NH secondary further tertiary quaternary mixture, acylation CH3COCl acetanilide protects NH2 o p to para reduces basicity, carbylamine primary CHCl3 KOH R-NC foul smell isocyanide test primary only foul secondary tertiary no, HNO2 primary N2 bubbles alcohol secondary yellow oily nitrosamine tertiary no reaction distinguishes.

Daily Analogy: Alkylation like adding friends over alkylation mixture. Acylation like wearing cap protects NH2 reduces basicity. Carbylamine foul smell like rotten cabbage alarm primary present. HNO2 test like three doors primary gas bubbles door, secondary oily layer door, tertiary no door no reaction.

Chemical Reactions - Alkylation Acylation Carbylamine

Revision Points - Easy:

Alkylation R-NH2+RX -> R2NH secondary further R3N R4N+ mixture over alkylation.
Acylation R-NH2+CH3COCl (CH3CO)2O -> amide R-NHCOCH3 acetanilide protects NH2 for electrophilic controls o p to para reduces basicity.
Carbylamine primary R-NH2+CHCl3+3KOH heat -> R-NC isocyanide foul extremely bad smell test primary only secondary tertiary no distinguishes.
HNO2 primary aliphatic N2 gas bubbles R-OH + N2 effervescence secondary yellow oily nitrosamine R2N-N=O carcinogenic tertiary no reaction distinguishes primary secondary tertiary.

6. Diazonium Salts - Cold Ice Chemistry

Diazonium salts R-N2+ X- contain N2+ group diazo. Aliphatic unstable not useful aromatic stable at low temp 0-5 C ice bath.

Preparation: aniline C6H5NH2 + NaNO2 sodium nitrite + 2 HCl at 0-5 C ice cold -> benzenediazonium chloride C6H5N2+Cl- + NaCl +2H2O. Reaction: C6H5NH2 + NaNO2 +2HCl 0-5 C -> C6H5N2+Cl- +NaCl+2H2O. Temperature must be 0-5 C if higher decomposes gives phenol N2 gas.

Properties: unstable explosive when dry, soluble in water, N2+ is excellent leaving group N2 gas leaves easily.

Reactions: Sandmeyer: C6H5N2+Cl- + CuCl HCl -> chlorobenzene C6H5Cl + N2 gas CuCl catalyst, C6H5N2+Cl- + CuBr HBr -> bromobenzene C6H5Br + N2, C6H5N2+Cl- + CuCN KCN -> benzonitrile C6H5CN + N2. Used to make haloarenes nitriles which cannot be made easily otherwise. Gattermann variant Cu powder instead of CuCl.

Replacement by OH: C6H5N2+Cl- + H2O warm -> phenol C6H5OH + N2 + HCl hydrolysis warm gives phenol.

Coupling reaction: diazonium + phenol or aniline alkaline medium gives azo dye -N=N- linkage coloured compounds. Example C6H5N2+Cl- + phenol C6H5OH NaOH -> p-hydroxyazobenzene orange dye C6H5-N=N-C6H4OH. Azo dyes yellow orange red used in textiles. Reaction at para position to OH NH2 if para blocked ortho.

Daily: azo dyes colourful clothes, diazonium cold chemistry ice bath.

Diazonium R-N2+ X- N2+ diazo aliphatic unstable aromatic stable low temp 0-5 ice bath | Prep aniline C6H5NH2+NaNO2+2HCl 0-5 ice cold benzenediazonium chloride C6H5N2+Cl-+NaCl+2H2O Reaction C6H5NH2+NaNO2+2HCl 0-5 C C6H5N2+Cl-+NaCl+2H2O Temp 0-5 higher decomposes phenol N2 | Properties unstable explosive dry soluble water N2+ excellent leaving group N2 leaves easily | Sandmeyer C6H5N2+Cl-+CuCl HCl chlorobenzene C6H5Cl+N2 CuCl catalyst C6H5N2+Cl-+CuBr HBr bromobenzene C6H5Br+N2 C6H5N2+Cl-+CuCN KCN benzonitrile C6H5CN+N2 make haloarenes nitriles not easily otherwise Gattermann Cu powder instead CuCl | Replacement OH C6H5N2+Cl-+H2O warm phenol C6H5OH+N2+HCl hydrolysis warm phenol | Coupling diazonium+phenol or aniline alkaline azo dye -N=N- coloured C6H5N2+Cl-+phenol C6H5OH NaOH p-hydroxyazobenzene orange dye C6H5-N=N-C6H4OH azo dyes yellow orange red textiles para to OH NH2 if para blocked ortho | Daily azo dyes colourful clothes diazonium cold ice bath

Visual Learning Method: Diazonium R-N2+ X- aliphatic unstable aromatic stable 0-5 ice bath, preparation aniline NaNO2 2HCl 0-5 benzenediazonium chloride NaCl 2H2O temp 0-5 higher decomposes phenol N2, unstable explosive dry soluble N2 excellent leaving group, Sandmeyer CuCl chlorobenzene CuBr bromobenzene CuCN benzonitrile N2, OH replacement warm phenol, coupling phenol aniline alkaline azo dye -N=N- orange dye p-hydroxyazobenzene yellow orange red textiles para OH NH2.

Daily Analogy: Diazonium like ice cream melts if warm unstable needs cold 0-5 ice bath. N2+ excellent leaving group like person eager to leave party N2 gas leaves easily. Sandmeyer like swapping N2+ with Cl Br CN using Cu catalyst magic exchange. Coupling like two aromatic rings linked by -N=N- bridge colourful azo dye clothes colourful.

Diazonium Salts - Cold Chemistry

Revision Points - Easy:

Diazonium R-N2+ X- aliphatic unstable aromatic stable low temp 0-5 ice bath.
Prep aniline + NaNO2 +2HCl 0-5 ice cold benzenediazonium chloride C6H5N2+Cl- +NaCl+2H2O temp must 0-5 higher decomposes phenol N2.
Properties unstable explosive dry soluble water N2+ excellent leaving group N2 leaves easily.
Sandmeyer CuCl chlorobenzene CuBr bromobenzene CuCN benzonitrile N2 used to make haloarenes nitriles Gattermann Cu powder.
Replacement OH H2O warm phenol C6H5OH+N2+HCl hydrolysis warm phenol.
Coupling diazonium+phenol or aniline alkaline azo dye -N=N- colourful orange dye p-hydroxyazobenzene yellow orange red textiles para to OH NH2.

7. Aniline - Preparation Properties Electrophilic Substitution

Preparation aniline from nitrobenzene C6H5NO2 + Sn HCl or Fe HCl or H2 Pd as earlier reduction Sn HCl -> aniline SnCl4 H2O. Lab: nitrobenzene + Sn conc HCl heat -> aniline + SnCl4 + H2O then NaOH to free aniline oily layer.

Properties: aniline weak base pKb 9.37 vs methylamine 3.38 larger pKb weaker base due to resonance delocalization lone pair into benzene ring 5 resonance structures negative on ring reduces availability. Acylation aniline + CH3COCl or (CH3CO)2O -> acetanilide C6H5NHCOCH3 protects NH2 reduces activation prevents oxidation controls nitration to para mainly.

Electrophilic substitution: NH2 strongly activating ortho para directing resonance donation activates ring strongly o p electron rich. But aniline too activated gives problems oxidation and tribromo. Bromination: aniline + Br2 water room temp immediately gives white precipitate 2,4,6-tribromoaniline three Br at o o p all positions due to strong activation. To get monobromo need to protect NH2 as acetanilide C6H5NHCOCH3 acetanilide NHCOCH3 less activating then Br2 CS2 low temp gives o and p bromoacetanilide then hydrolysis NaOH gives o and p bromoaniline.

Nitration: direct nitration HNO3 H2SO4 gives oxidation tar plus m-nitroaniline unexpected because aniline protonated in acid medium NH3+ anilinium deactivating meta directing so mixture o m p nitration mixture. To get p-nitroaniline protect as acetanilide then nitration HNO3 H2SO4 gives p-nitroacetanilide para mainly then hydrolysis gives p-nitroaniline. So protection needed for controlled nitration.

Daily: aniline used to make dyes drugs, acetanilide protection strategy like wearing helmet.

Prep aniline nitrobenzene C6H5NO2+Sn HCl Fe HCl H2 Pd aniline SnCl4 H2O Lab nitrobenzene+Sn conc HCl heat aniline+SnCl4 H2O NaOH free oily layer | Properties weak base pKb 9.37 methylamine 3.38 larger pKb weaker base resonance delocalization lone pair benzene ring 5 resonance negative on ring reduces availability Acylation aniline+CH3COCl or (CH3CO)2O acetanilide C6H5NHCOCH3 protects NH2 reduces activation prevents oxidation controls nitration to para mainly | Electrophilic NH2 strongly activating o p directing resonance donation activates ring strongly o p electron rich but too activated oxidation tribromo | Bromination aniline+Br2 water room temp immediate white precipitate 2,4,6-tribromoaniline three Br o o p strong activation To monobromo protect NH2 as acetanilide NHCOCH3 less activating Br2 CS2 low temp o p bromoacetanilide hydrolysis NaOH o p bromoaniline | Nitration direct HNO3 H2SO4 oxidation tar m-nitroaniline unexpected aniline protonated acid medium NH3+ anilinium deactivating meta directing mixture o m p To p-nitroaniline protect as acetanilide nitration HNO3 H2SO4 p-nitroacetanilide para mainly hydrolysis p-nitroaniline protection needed controlled nitration | Daily aniline dyes drugs acetanilide protection helmet

Visual Learning Method: Prep nitrobenzene Sn HCl aniline SnCl4 H2O NaOH oily layer, properties weak base pKb 9.37 vs 3.38 resonance 5 structures, acylation acetanilide protects NH2 reduces activation controls para, electrophilic NH2 strongly activating o p directing resonance donation strongly but too activated tribromo, bromination Br2 water white ppt 2,4,6-tribromoaniline three Br o o p, monobromo protect acetanilide Br2 CS2 o p bromoacetanilide hydrolysis bromoaniline, nitration direct HNO3 H2SO4 oxidation tar m-nitroaniline unexpected NH3+ meta directing mixture, protect acetanilide nitration p-nitroacetanilide hydrolysis p-nitroaniline protection needed.

Daily Analogy: Aniline too activated like overenthusiastic person gives tribromo all positions white precipitate immediate. Protection as acetanilide like putting cap reduces enthusiasm controlled mono substitution para mainly helmet protects from overreaction. Nitration direct gives unexpected meta because acid protonates NH2 to NH3+ deactivating meta directing like person becomes angry in acid medium changes behavior.

Aniline - Preparation Properties

Revision Points - Easy:

Prep nitrobenzene Sn HCl Fe HCl H2 Pd aniline SnCl4 H2O Lab Sn conc HCl heat aniline NaOH oily layer.
Weak base pKb 9.37 vs methylamine 3.38 resonance delocalization lone pair into benzene 5 resonance reduces availability acylation acetanilide protects NH2 reduces activation prevents oxidation controls para.
NH2 strongly activating o p directing resonance donation strongly activates but too activated tribromo.
Bromination Br2 water room temp white ppt 2,4,6-tribromoaniline three Br o o p strong activation monobromo protect acetanilide Br2 CS2 o p bromoacetanilide hydrolysis o p bromoaniline.
Nitration direct HNO3 H2SO4 oxidation tar m-nitroaniline unexpected protonated NH3+ anilinium deactivating meta directing mixture protect acetanilide nitration p-nitroacetanilide para hydrolysis p-nitroaniline protection needed controlled.

8. Everyday Uses - Drugs Dyes Nylon

Look around: paracetamol medicine for fever headache contains aniline derivative p-hydroxyacetanilide, azo dyes in colourful T-shirts orange red yellow from diazonium coupling, nylon 6,6 from hexamethylenediamine H2N(CH2)6NH2 + adipic acid polyamide strong fibres carpets clothes, rubber vulcanization accelerators aniline derivatives, amino acids building blocks proteins NH2-CH(R)-COOH proteins muscles hair, aniline used to make polyurethane foam mattress cushion, pesticides, explosives.

Amines in biology: neurotransmitters dopamine serotonin contain amine group signals brain, amino acids essential lysine etc.

Industrial: aniline makes MDI methylene diphenyl diisocyanate for polyurethane, dyes aniline dyes colourful, drugs sulfa drugs antibacterial.

Paracetamol fever headache p-hydroxyacetanilide aniline derivative | Azo dyes colourful T-shirts orange red yellow diazonium coupling | Nylon 6,6 hexamethylenediamine H2N(CH2)6NH2+adipic acid polyamide strong fibres carpets clothes | Rubber vulcanization accelerators aniline derivatives | Amino acids building blocks proteins NH2-CH(R)-COOH proteins muscles hair | Polyurethane foam mattress cushion MDI methylene diphenyl diisocyanate | Pesticides explosives | Biology neurotransmitters dopamine serotonin amine signals brain amino acids essential lysine | Industrial aniline MDI polyurethane dyes aniline dyes colourful drugs sulfa antibacterial

Visual Learning Method: Paracetamol medicine fever headache p-hydroxyacetanilide, azo dyes T-shirts orange red yellow coupling, nylon 6,6 hexamethylenediamine adipic acid polyamide fibres carpets clothes, rubber accelerators, amino acids proteins NH2-CH(R)-COOH muscles hair, polyurethane foam mattress cushion MDI, neurotransmitters dopamine serotonin brain signals.

Daily Analogy: Amines like versatile actors in daily life medicine paracetamol relieves fever, clothes colourful dyes, strong nylon fibres carpets, proteins muscles hair building blocks amino acids, brain signals dopamine serotonin messengers amine group signal.

Everyday Uses - Drugs Dyes Nylon

Revision Points - Easy:

Paracetamol p-hydroxyacetanilide aniline derivative medicine fever headache.
Azo dyes colourful T-shirts orange red yellow diazonium coupling phenol aniline.
Nylon 6,6 hexamethylenediamine + adipic acid polyamide strong fibres carpets clothes.
Amino acids NH2-CH(R)-COOH proteins building blocks muscles hair.
Polyurethane foam mattress cushion MDI from aniline rubber accelerators pesticides explosives.
Neurotransmitters dopamine serotonin amine signals brain amino acids essential lysine.

Gold Reference Table - All Formulas + Daily Life Visual - High Quality

Concept	Formula / Easy Fact	Daily Life Visual / Uses
Classification	Primary R-NH2 one alkyl methylamine fishy Secondary R2-NH two alkyl dimethylamine Tertiary R3-N three alkyl trimethylamine fish market Quaternary R4N+ X- four alkyl positive tetraethylammonium phase transfer Aromatic aniline C6H5NH2 benzene+NH2 toluidine CH3C6H4NH2 o m p	Fish market trimethylamine onion garlic primary one child secondary two tertiary three crowded quaternary four positive
IUPAC	Alkanamine methanamine CH3NH2 ethanamine CH3CH2NH2 N-methylmethanamine CH3NHCH3 N,N-dimethylmethanamine (CH3)3N benzenamine C6H5NH2 aniline	Names alkanamine benzenamine
Structure	sp3 pyramidal umbrella lone pair top angle ~107 lone pair repulsion rapid inversion umbrella flips not optically active	Umbrella lone pair top flips quickly
H-bonding boiling	Primary secondary N-H H-bond N-H...N higher boiling than tertiary no N-H ethylamine 16.6 dimethylamine 7.4 trimethylamine 2.8 similar mass primary higher more H-bonding All H-bond with water small soluble fully larger less soluble non-polar dominates fishy	Holding hands primary two hands higher boiling tertiary no hands lower boiling small soluble water
Prep nitro reduction	R-NO2+Sn HCl Fe HCl H2 Pd R-NH2 nitrobenzene C6H5NO2 Sn HCl aniline SnCl4 H2O industrial H2 Ni most common aniline	Nitro to aniline reduction Sn HCl
Prep haloalkanes NH3	R-X+NH3 excess R-NH2+HX mixture primary secondary tertiary quaternary not pure over alkylation R-NH2 more nucleophilic than NH3 further R2NH etc excess NH3 minimize but mixture	Mixture party overcrowding primary brings friends secondary tertiary
Prep nitriles amides	RCN+LiAlH4 H2 Ni primary RCH2NH2 adds one C CH3CN CH3CH2NH2 ethylamine RCONH2+LiAlH4 RCH2NH2 same C Hofmann bromamide RCONH2+Br2 NaOH R-NH2 one C less removes CO carbonate CH3CONH2 Br2 NaOH CH3NH2 methylamine Reaction RCONH2+Br2+4NaOH R-NH2+Na2CO3+2NaBr+2H2O	Adds one C same C one C less trimming tail
Prep Gabriel	Phthalimide+KOH potassium phthalimide+RX N-alkyl phthalimide NaOH hydrolysis R-NH2 primary+phthalic acid pure primary no secondary tertiary primary only	VIP entry only one guest pure primary no overcrowding
Basicity	N lone pair donates H+ NH4+ RNH3+ Lewis base stronger more available lone pair Alkyl +I increases basicity gas tertiary>secondary>primary>ammonia +I dominates aqueous secondary>primary>tertiary>ammonia methyl (CH3)2NH secondary most basic ethyl (C2H5)2NH secondary>tertiary>primary>ammonia solvation H-bonding stabilizes ammonium more H more solvation more stable more basic balance	Generosity lone pair donation alkyl donate money more basic gas tertiary most aqueous secondary most solvation friends support
Aniline basicity	C6H5NH2 very weak base weaker than aliphatic lone pair delocalized benzene resonance 5 structures negative on ring reduces availability pKb aniline 9.37 methylamine 3.38 larger pKb weaker EW NO2 o p decreases basicity p-NO2 very weak non-basic ED CH3 OCH3 o p increases basicity p-CH3 slightly more basic than aniline	Lone pair busy meeting resonance less available weaker base NO2 withdraws poor p-NO2 very weak
Alkylation	R-NH2+RX R2NH+HX further R3N R4N+ X- mixture over alkylation CH3NH2+CH3CH2Br CH3NHCH2CH3 N-ethylmethylamine secondary	Adding friends mixture over alkylation
Acylation	R-NH2+CH3COCl acetyl chloride or (CH3CO)2O anhydride amide R-NHCOCH3+HCl aniline C6H5NH2+CH3COCl C6H5NHCOCH3 acetanilide protects NH2 further electrophilic avoids oxidation controls o p to para mainly reduces basicity lone pair delocalized carbonyl	Wearing cap protects NH2 reduces activation para mainly helmet
Carbylamine	Primary R-NH2+CHCl3+3KOH alcoholic heat R-NC isocyanide foul extremely bad smell+3KCl+3H2O test primary only primary foul secondary tertiary no CH3NH2+CHCl3+3KOH CH3NC methyl isocyanide foul distinguishes primary secondary tertiary sensitive test	Rotten cabbage foul smell alarm primary present
HNO2 test	Primary aliphatic R-NH2+HNO2 NaNO2 HCl cold R-OH+N2 gas bubbles+H2O brisk effervescence CH3CH2NH2+HNO2 CH3CH2OH+N2 bubbles Secondary R2NH+HNO2 R2N-N=O nitrosamine yellow oily layer carcinogenic N-nitrosamine Tertiary R3N+HNO2 no reaction solution unchanged no gas no oil distinguishes	Three doors primary gas bubbles door secondary oily layer door tertiary no door
Diazonium prep	R-N2+ X- N2+ diazo aliphatic unstable aromatic stable low temp 0-5 ice bath Aniline C6H5NH2+NaNO2+2HCl 0-5 ice cold benzenediazonium chloride C6H5N2+Cl-+NaCl+2H2O Reaction C6H5NH2+NaNO2+2HCl 0-5 C6H5N2+Cl-+NaCl+2H2O Temp 0-5 higher decomposes phenol N2	Ice cream melts warm unstable needs cold 0-5 ice bath
Diazonium properties	Unstable explosive dry soluble water N2+ excellent leaving group N2 leaves easily	Person eager to leave party N2 gas leaves easily
Sandmeyer	C6H5N2+Cl-+CuCl HCl chlorobenzene C6H5Cl+N2 CuCl catalyst C6H5N2+Cl-+CuBr HBr bromobenzene C6H5Br+N2 C6H5N2+Cl-+CuCN KCN benzonitrile C6H5CN+N2 make haloarenes nitriles not easily otherwise Gattermann Cu powder instead CuCl	Swapping N2+ with Cl Br CN Cu catalyst magic exchange
OH replacement coupling	C6H5N2+Cl-+H2O warm phenol C6H5OH+N2+HCl hydrolysis warm phenol Coupling diazonium+phenol or aniline alkaline azo dye -N=N- coloured C6H5N2+Cl-+phenol C6H5OH NaOH p-hydroxyazobenzene orange dye C6H5-N=N-C6H4OH azo dyes yellow orange red textiles para to OH NH2 if para blocked ortho	Two rings linked -N=N- bridge colourful azo dye clothes
Aniline prep properties	Nitrobenzene C6H5NO2+Sn HCl Fe HCl H2 Pd aniline SnCl4 H2O Lab Sn conc HCl heat aniline+SnCl4 H2O NaOH free oily layer Weak base pKb 9.37 methylamine 3.38 larger pKb weaker base resonance delocalization lone pair benzene ring 5 resonance negative on ring reduces availability Acylation aniline+CH3COCl or (CH3CO)2O acetanilide C6H5NHCOCH3 protects NH2 reduces activation prevents oxidation controls nitration to para mainly	Weak base resonance 5 structures protection helmet
Aniline electrophilic	NH2 strongly activating o p directing resonance donation activates ring strongly o p electron rich but too activated oxidation tribromo Bromination aniline+Br2 water room temp immediate white ppt 2,4,6-tribromoaniline three Br o o p strong activation To monobromo protect NH2 as acetanilide NHCOCH3 less activating Br2 CS2 low temp o p bromoacetanilide hydrolysis NaOH o p bromoaniline Nitration direct HNO3 H2SO4 oxidation tar m-nitroaniline unexpected aniline protonated acid medium NH3+ anilinium deactivating meta directing mixture o m p To p-nitroaniline protect as acetanilide nitration HNO3 H2SO4 p-nitroacetanilide para mainly hydrolysis p-nitroaniline protection needed controlled nitration	Overenthusiastic person tribromo white ppt immediate protection cap reduces enthusiasm controlled mono para helmet angry in acid NH3+ meta directing
Everyday uses	Paracetamol p-hydroxyacetanilide aniline derivative fever headache Azo dyes colourful T-shirts orange red yellow diazonium coupling Nylon 6,6 hexamethylenediamine H2N(CH2)6NH2+adipic acid polyamide strong fibres carpets clothes Rubber vulcanization accelerators aniline derivatives Amino acids building blocks proteins NH2-CH(R)-COOH proteins muscles hair Polyurethane foam mattress cushion MDI methylene diphenyl diisocyanate Pesticides explosives Biology neurotransmitters dopamine serotonin amine signals brain amino acids essential lysine Industrial aniline MDI polyurethane dyes aniline dyes colourful drugs sulfa antibacterial	Medicine fever headache colourful T-shirts strong nylon fibres carpets proteins muscles hair mattress cushion brain signals dopamine serotonin messengers

Final Exam Ready Revision - Easy Day-to-Day Hooks - High Quality:

Amines NH3 derivatives H replaced by alkyl aryl primary R-NH2 one alkyl methylamine fishy ethylamine secondary R2-NH two alkyl dimethylamine tertiary R3-N three alkyl trimethylamine fish market fishy onion garlic quaternary R4N+ X- four alkyl positive tetraethylammonium phase transfer aromatic aniline C6H5NH2 benzene+NH2 dyes drugs toluidine methyl aniline o m p isomers primary one child secondary two tertiary three crowded quaternary four positive.
IUPAC alkanamine methanamine methylamine ethanamine ethylamine N-methylmethanamine dimethylamine N,N-dimethylmethanamine trimethylamine benzenamine aniline structure sp3 pyramidal umbrella lone pair top angle 107 lone pair repulsion rapid inversion umbrella flips inside out quickly not optically active generally H-bonding primary secondary N-H H-bond N-H...N higher boiling than tertiary no N-H ethylamine 16.6 dimethylamine 7.4 trimethylamine 2.8 similar mass primary higher more H-bonding all H-bond with water N accepts H from water O-H...N N-H donates to water O small soluble fully larger less soluble non-polar dominates fishy smell holding hands primary two hands higher boiling tertiary no hands lower boiling umbrella lone pair top.
Preparation nitro reduction R-NO2 Sn HCl Fe HCl H2 Pd R-NH2 nitrobenzene Sn HCl aniline SnCl4 H2O industrial H2 Ni most common aniline haloalkanes R-X+NH3 excess R-NH2+HX mixture primary secondary tertiary quaternary not pure over alkylation R-NH2 more nucleophilic than NH3 further RX secondary R2NH excess NH3 minimize but mixture not good pure primary nitriles RCN LiAlH4 H2 Ni primary RCH2NH2 adds one C more than alkyl halide CH3CN CH3CH2NH2 ethylamine adds CH2 amides RCONH2 LiAlH4 RCH2NH2 primary same C count amide to amine Hofmann bromamide RCONH2+Br2 NaOH R-NH2 one C less removes CO as carbonate CH3CONH2 Br2 NaOH CH3NH2 methylamine one C less acetamide to methylamine Reaction RCONH2+Br2+4NaOH R-NH2+Na2CO3+2NaBr+2H2O Gabriel phthalimide synthesis pure primary avoids mixture phthalimide KOH potassium phthalimide RX N-alkyl phthalimide NaOH hydrolysis R-NH2 primary+phthalic acid pure primary no secondary tertiary primary only mixture party overcrowding VIP entry only one guest pure primary trimming tail one C less.
Basic N lone pair donates H+ NH4+ RNH3+ Lewis base stronger base more available lone pair alkyl +I electron donating pushes electrons to N increases electron density stronger base gas phase tertiary greater than secondary greater than primary greater than ammonia +I dominates aqueous water solvation H-bonding stabilizes ammonium more H on N more solvation more stable more basic balance order aqueous methyl amines (CH3)2NH secondary most basic secondary greater than primary greater than tertiary greater than ammonia ethyl amines secondary greater than tertiary greater than primary greater than ammonia (C2H5)2NH most basic aniline C6H5NH2 very weak base weaker than aliphatic lone pair delocalized benzene resonance 5 structures negative on ring reduces availability pKb aniline 9.37 methylamine 3.38 larger pKb weaker base EW NO2 o p decreases basicity p-NO2 very weak non-basic ED CH3 OCH3 o p increases basicity p-CH3 slightly more basic than aniline boiling higher than alkanes H-bonding primary secondary N-H...N tertiary no N-H no H-bond between themselves lower boiling than primary secondary generosity lone pair donation alkyl donate money more basic aniline busy meeting resonance less available weaker base NO2 withdraws poor less basic solvation friends support more H more friends H-bonding support more stable more basic.
Chemical alkylation R-NH2+RX R2NH+HX further R3N R4N+ X- mixture over alkylation CH3NH2+CH3CH2Br CH3NHCH2CH3 N-ethylmethylamine secondary acylation R-NH2+CH3COCl acetyl chloride or (CH3CO)2O anhydride amide R-NHCOCH3+HCl aniline C6H5NH2+CH3COCl C6H5NHCOCH3 acetanilide protects NH2 further electrophilic avoids oxidation controls o p to para mainly reduces basicity lone pair delocalized carbonyl carbylamine primary R-NH2+CHCl3+3KOH alcoholic heat R-NC isocyanide foul extremely bad smell+3KCl+3H2O test primary only primary foul secondary tertiary no CH3NH2+CHCl3+3KOH CH3NC methyl isocyanide foul distinguishes primary secondary tertiary sensitive test HNO2 nitrous acid distinguishes primary secondary tertiary primary aliphatic R-NH2+HNO2 NaNO2 HCl cold R-OH+N2 gas bubbles+H2O brisk effervescence CH3CH2NH2+HNO2 CH3CH2OH+N2 bubbles secondary R2NH+HNO2 R2N-N=O nitrosamine yellow oily layer carcinogenic N-nitrosamine tertiary R3N+HNO2 no reaction solution unchanged no gas no oil distinguishes adding friends mixture wearing cap protects NH2 reduces activation para mainly helmet rotten cabbage foul smell alarm primary present three doors primary gas bubbles door secondary oily layer door tertiary no door.
Diazonium R-N2+ X- N2+ diazo aliphatic unstable aromatic stable low temp 0-5 ice bath aniline C6H5NH2+NaNO2+2HCl 0-5 ice cold benzenediazonium chloride C6H5N2+Cl-+NaCl+2H2O Reaction C6H5NH2+NaNO2+2HCl 0-5 C6H5N2+Cl-+NaCl+2H2O Temp 0-5 higher decomposes phenol N2 properties unstable explosive dry soluble water N2+ excellent leaving group N2 leaves easily Sandmeyer C6H5N2+Cl-+CuCl HCl chlorobenzene C6H5Cl+N2 CuCl catalyst C6H5N2+Cl-+CuBr HBr bromobenzene C6H5Br+N2 C6H5N2+Cl-+CuCN KCN benzonitrile C6H5CN+N2 make haloarenes nitriles not easily otherwise Gattermann Cu powder instead CuCl replacement OH C6H5N2+Cl-+H2O warm phenol C6H5OH+N2+HCl hydrolysis warm phenol coupling diazonium+phenol or aniline alkaline azo dye -N=N- coloured C6H5N2+Cl-+phenol C6H5OH NaOH p-hydroxyazobenzene orange dye C6H5-N=N-C6H4OH azo dyes yellow orange red textiles para to OH NH2 if para blocked ortho daily azo dyes colourful clothes diazonium cold ice bath ice cream melts warm unstable needs cold ice bath person eager to leave party N2 gas leaves easily swapping N2+ with Cl Br CN Cu catalyst magic exchange two rings linked -N=N- bridge colourful azo dye clothes.
Aniline prep nitrobenzene C6H5NO2+Sn HCl Fe HCl H2 Pd aniline SnCl4 H2O Lab Sn conc HCl heat aniline+SnCl4 H2O NaOH free oily layer weak base pKb 9.37 methylamine 3.38 larger pKb weaker base resonance delocalization lone pair benzene ring 5 resonance negative on ring reduces availability acylation aniline+CH3COCl or (CH3CO)2O acetanilide C6H5NHCOCH3 protects NH2 reduces activation prevents oxidation controls nitration to para mainly electrophilic NH2 strongly activating o p directing resonance donation activates ring strongly o p electron rich but too activated oxidation tribromo bromination aniline+Br2 water room temp immediate white precipitate 2,4,6-tribromoaniline three Br o o p strong activation to monobromo protect NH2 as acetanilide NHCOCH3 less activating Br2 CS2 low temp o p bromoacetanilide hydrolysis NaOH o p bromoaniline nitration direct HNO3 H2SO4 oxidation tar m-nitroaniline unexpected aniline protonated acid medium NH3+ anilinium deactivating meta directing mixture o m p to p-nitroaniline protect as acetanilide nitration HNO3 H2SO4 p-nitroacetanilide para mainly hydrolysis p-nitroaniline protection needed controlled nitration daily aniline dyes drugs acetanilide protection helmet overenthusiastic person tribromo white ppt immediate protection cap reduces enthusiasm controlled mono para helmet angry in acid NH3+ meta directing.
Everyday paracetamol fever headache p-hydroxyacetanilide aniline derivative azo dyes colourful T-shirts orange red yellow diazonium coupling nylon 6,6 hexamethylenediamine H2N(CH2)6NH2+adipic acid polyamide strong fibres carpets clothes rubber vulcanization accelerators aniline derivatives amino acids building blocks proteins NH2-CH(R)-COOH proteins muscles hair polyurethane foam mattress cushion MDI methylene diphenyl diisocyanate pesticides explosives biology neurotransmitters dopamine serotonin amine signals brain amino acids essential lysine industrial aniline MDI polyurethane dyes aniline dyes colourful drugs sulfa antibacterial versatile actors medicine relieves fever clothes colourful dyes strong nylon fibres carpets proteins muscles hair building blocks brain signals messengers.