AMINA Senyawa yang mengandung gugus NH2 Strukrur : RNH2 Jenis : Amina primer (1o) Amina sekunder (2o) Amina tersier (3o)

Tata Nama Amina alifatik sederhana dinamakan dengan gugus alkil yang terikat pada atom N dan diberi akhiran amin.

Sistem IUPAC, gugus NH2 dinamakan gugus amino

Tata Nama : Jika atom N mengikat 4 gugus hidrokarbon akan bermuatan positif dam dikenal sebagai ion ammonium kuartener

Tata Nama : Senyawa yang mengandung gugus –NH2 pada cincin benzena dinamakan sebagai derivat anilin.

Tata Nama : Senyawa siklis dimana satu atom C atau lebih diganti dengan atom nitrogen, diberi nama khusus sebagai heterosiklik amin.

Beberapa Contoh Senyawa Heterosiklis Amin Alkaloid : senyawa yang mengandung nitrogen yang bersifat basa dari tumbuhan dan hewan. Senyawa ini mempunyai struktur yang rumit dan sifat farmakologis (faali) yang nyata Nikotin dari tembakau Porfirin : senyawa heterosiklis yang mengandung 4 cicin pirol yang saling berikatan. Porfirin membentuk kompleks dengan ion logam. Apabila membentuk kompleks dengan Fe membentuk besi-porfirin yang menyebabkan warna darah merah pada darah arteri  Hemoglobin

Contoh Senyawa Heterosiklis Klorofil berwarna hijau adalah kompleks Mg dengan porfirin yang termodifikasi.

Sifat-Sifat Fisik Amina : Amina 1 dan 2 bersifat polar karena mampu membentuk ikatan hydrogen intermolekuler. Larut dalam air karena mampu membentuk ikatan hidrogen dengan air. Ikatan hidrogen

Measures of Basicity The basicity of amines may be measured by: 1) Kb 2) pKb 3) Ka of conjugate acid 4) pKa of conjugate acid 6

Basicity Constant (Kb) and pKb Kb is the equilibrium constant for the reaction: R3N + H H OH •• – • • OH •• R3N • • + + [R3NH+][HO–] Kb = [R3N] and pKb = - log Kb 2

Ka and pKa of Conjugate Acid Ka is the equilibrium constant for the dissociation of the conjugate acid of the amine: R3N • • + H H+ [R3N][H+] Ka = [R3NH+] and pKa = - log Ka 3

Relationships between acidity and basicity constants Ka Kb = 10-14 pKa + pKb = 14 3

The beverage reportedly produced using the extract of leaves of Erythroxylon coca: The compound: cocaine, it is an organic base: Merck Index, #2450, 11th ed.: Caution: May be habit forming….

Acid -Base Chemistry (Physical Properties) m.p. 98 oC b.p. (very volatile > 90 oC) Solubility: Water: 1.67 x 10-3 g/mL CHCl3: 1.43 g/mL Ether: 0.29 g/mL What structural feature makes cocaine a base? What simple compound can you relate it to?

“Regular” Cocaine Conjugate Acid of Cocaine (Physical Properties) m.p. >195 oC Solubility: Water: 2.5 g/mL CHCl3: 0.08 g/mL Ether: insoluble What accounts for the differences in solubilities of the base and conjugate acid?

Acid -Base Reactions

Acid Base Reactions

Basicity of Amines in Aqueous Solution Amine Conj. Acid pKa NH3 NH4+ 9.3 CH3CH2NH2 CH3CH2NH3+ 10.8 CH3CH2NH3+ is a weaker acid than NH4+; therefore, CH3CH2NH2 is a stronger base than NH3. 6

Effect of Structure on Basicity 1. Alkylamines are slightly stronger bases than ammonia. 2. Alkylamines differ very little in basicity. 5

Basicity of Amines in Aqueous Solution Amine Conj. Acid pKa NH3 NH4+ 9.3 CH3CH2NH2 CH3CH2NH3+ 10.8 (CH3CH2)2NH (CH3CH2)2NH2+ 11.1 (CH3CH2)3N (CH3CH2)3NH+ 10.8 Notice that the difference separating a primary, secondary, and tertiary amine is only 0.3 pK units. 6

Effect of Structure on Basicity 1. Alkylamines are slightly stronger bases than ammonia. 2. Alkylamines differ very little in basicity. 3. Arylamines are much weaker bases than ammonia. 5

Basicity of Amines in Aqueous Solution Amine Conj. Acid pKa NH3 NH4+ 9.3 CH3CH2NH2 CH3CH2NH3+ 10.8 (CH3CH2)2NH (CH3CH2)2NH2+ 11.1 (CH3CH2)3N (CH3CH2)3NH+ 10.8 C6H5NH2 C6H5NH3+ 4.6 6

Decreased basicity of arylamines NH2 •• H OH •• + Aniline (reactant) is stabilized by conjugation of nitrogen lone pair with ring p system. This stabilization is lost on protonation. NH3 + – • • OH •• + 2

Decreased basicity of arylamines Increasing delocalization makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine. C6H5NH2 (C6H5)2NH (C6H5)3N Kb 3.8 x 10-10 6 x 10-14 ~10-19 2

Effect of Substituents on Basicity of Arylamines 1. Alkyl groups on the ring increase basicity, but only slightly (less than 1 pK unit). 2. Electron withdrawing groups, especially ortho and/or para to amine group, decrease basicity and can have a large effect. 5

Basicity of Arylamines X NH2 X NH3+ X pKb pKa H 9.4 4.6 CH3 8.7 5.3 CF3 11.5 2.5 O2N 13.0 1.0 7

p-Nitroaniline NH2 O N – + O N – NH2 + + •• • • + O N – •• • • NH2 + + Lone pair on amine nitrogen is conjugated with p-nitro group—more delocalized than in aniline itself. Delocalization lost on protonation. 2

Aniline is 3800 times more basic than p-nitroaniline. Effect is Cumulative Aniline is 3800 times more basic than p-nitroaniline. Aniline is ~1,000,000,000 times more basic than 2,4-dinitroaniline. 2

(resembles an arylamine in basicity) Heterocyclic Amines N •• N H •• is more basic than piperidine pyridine Kb = 1.6 x 10-3 Kb = 1.4 x 10-9 (an alkylamine) (resembles an arylamine in basicity) 9

Preparation and Reactions of Amines 3

The Gabriel Synthesis of Primary Amines

Reductive Amination 3

Synthesis of Amines via Reductive Amination In reductive amination, an aldehyde or ketone is subjected to catalytic hydrogenation in the presence of ammonia or an amine. O C R R' fast NH C R R' + NH3 + H2O The aldehyde or ketone equilibrates with the imine faster than hydrogenation occurs. 12

Synthesis of Amines via Reductive Amination The imine undergoes hydrogenation faster than the aldehyde or ketone. An amine is the product. O C R R' fast NH C R R' + NH3 + H2O NH2 R R' C H H2, Ni 12

Example: Ammonia gives a primary amine. H2, Ni O H NH2 + NH3 ethanol (80%) NH via: 18

Example: Primary amines give secondary amines CH3(CH2)5CH O + H2N H2, Ni ethanol CH3(CH2)5CH2NH (65%) 18

Example: Primary amines give secondary amines CH3(CH2)5CH O + H2N H2, Ni ethanol CH3(CH2)5CH2NH (65%) N CH3(CH2)5CH via: 18

Example: Secondary amines give tertiary amines H CH3CH2CH2CH O + H2, Ni, ethanol N CH2CH2CH2CH3 (93%) 18

Reductive Amination Is Versatile Ammonia, primary amines, and secondary amines yield primary, secondary, and tertiary amines, respectively

Mechanism of Reductive Amination Imine is intermediate

Hofmann and Curtius Rearrangements Carboxylic acid derivatives can be converted into primary amines with loss of one carbon atom by both the Hofmann rearrangement and the Curtius rearrangement

Hofmann Rearrangement RCONH2 reacts with Br2 and base Gives high yields of arylamines and alkylamines

Curtius Rearrangement Heating an acyl azide prepared from substitution an acid chloride Migration of R from C=O to the neighboring nitrogen with simultaneous loss of a leaving group

COPE REACTION N-OXIDE LESS HINDERED BETA HYDROGEN SYN ELIMINATION

Cope Elimination Reaction Amine Oxides Undergo a Cope Elimination Reaction

COPE EXAMPLE Mild conditions

Reactions of Amines Alkylation and acylation have already been presented

Arylamines Are Not Useful for Friedel-Crafts Reactions The amino group forms a Lewis acid–base complex with the AlCl3 catalyst, preventing further reaction Therefore we use the corresponding amide

Diazonium Salts: The Sandmeyer Reaction Primary arylamines react with HNO2, yielding stable arenediazonium salts NaNO2 + HCl HONO

Uses of Arenediazonium Salts The N2 group can be replaced by a nucleophile

Diverse Reactions of Arenediazonium Salts Sequence of (1) nitration, (2) reduction, (3) diazotization, and (4) nucleophilic substitution leads to many different products

Preparation of Aryl Halides Reaction of an arenediazonium salt with CuCl or CuBr gives aryl halides (Sandmeyer Reaction) Aryl iodides form from reaction with NaI without a copper(I) salt

Aryl Nitriles and Carboxylic Acids An arenediazonium salt and CuCN yield the nitrile, ArCN, which can be hydrolyzed to ArCOOH

Formation of Phenols (ArOH) From reaction of the arenediazonium salt with copper(I) oxide in an aqueous solution of copper(II) nitrate

Reduction to a Hydrocarbon By treatment of a diazonium salt with hypophosphorous acid, H3PO2

Mechanism of Diazonium Replacement Through radical (rather than polar or ionic) pathways

Diazonium Coupling Reactions Arenediazonium salts undergo a coupling reaction with activated aromatic rings, such as phenols and arylamines, to yield brightly colored azo compounds, ArN=NAr

How Diazonium Coupling Occurs The electophilic diazonium ion reacts with the electron-rich ring of a phenol or arylamine Usually occurs at the para position but goes ortho if para is blocked

Azo Dyes Azo-coupled products have extended  conjugation that lead to low energy electronic transitions that occur in visible light (dyes)