AMINES Classification Primary amine Secondary amine Tertiary amine
- Slides: 52
AMINES
Classification Primary amine Secondary amine Tertiary amine
Quaternary ammonium compound
Aliphatic amines Aromatic amines
Examples of nomenclature
Cyclic amines
Structure and bonding in amines sp 3 C-N-C angle C-N bond length 108° 1. 47Å Trimethylamine
Structure and bonding in amines Chiral carbon Chiral nitrogen?
Pyramidal inversion in amines fast sp 3 sp 2 (planar) Energy barrier: 6 kcal/mol (25 k. J/mol) at room temp.
Physical properties of some amines Compound M. p (°C) B. p (°C) Ammonia -77. 7 -33. 3 Methylamine Ethylamine tert-Butylamine Aniline -94 -81 -67. 5 -6. 3 16. 6 44. 4 184. 1 Dimethylamine Diisopropylamine Pyrrolidine -93 -48 -61 2 7. 4 56. 3 84 89 Trimethylamine Triethylamine N-methylpyrrolidine -117 -114 -21 3 89. 3 81
Hydrogen bonding of amines Not possible for tertiary amines Hydrogen bonds are also formed with water Amines with fewer than 5 carbons are water-soluble
Basicity of amines Because of nitrogen lone pair amines are both basic and nucleophilic An amine (a Lewis base) An acid A salt Amines are much more basic than alcohols, ethers, or water.
Basicity of amines Deprotonation of amine salt by water is used as measure of amine basicity Stronger acid (lower p. Ka value) Weaker conjugated base Weaker acid Stronger conjugated base (higher p. Ka value) p. Ka = -log Ka Ka = Keq [H 2 O] = [H 3 O+][RNH 2]/[RNH 3+]
Basicity of some alkylamines Name Structure p. Ka of ammonium ion Ammonia NH 3 9. 26 CH 3 NH 2 CH 3 CH 2 NH 2 10. 64 10. 75 Dimethylamine Diethylamine Pyrrolidine (CH 3)2 NH (CH 3 CH 2)2 NH (CH 2)4 NH 10. 73 10. 94 11. 27 Trimethylamine Triethylamine (CH 3)3 N (CH 3 CH 2)3 N 9. 79 10. 75 Methylamine Ethylamine
Note the diference in basicity of amine and amide nitrogen Amides are completely nonbasic Resonance stabilization of amide
After amide protonation No resonance stabilization Inductive destabilization of the positive charge
Energy profiles for amine and amide protonation Energy RCONH 3+ RNH 2 RCONH 2 Reaction progress
Aromatic amines Resonance structures of aniline Resonance structures after protonation of aniline Arylamines are less basic than alkylamines p. Ka for aniline = 4. 63
Comparison of basicity – arylamines vs. alkylamines Energy RNH 3+ G 0 alkylamine RNH 2 + H 2 O Ar. NH 3+ G 0 arylamine Resonance stabilization Ar. NH 2 + H 2 O Reaction progress
Basicity of para-substituted anilines Y p. Ka Stronger base Weaker base -NH 2 6. 15 EDG -OCH 3 5. 34 -CH 3 5. 08 (activating ring in electrophilic substitution) Stabilize protonated amino group -H 4. 63 -Cl 3. 98 -Br 3. 86 -CN 1. 74 -NO 2 1. 00 EWG (deactivating ring in electrophilic substitution) Stabilize nonprotonated amino group
Energy profiles for protonation of para-substituted anilines Energy Y = EWG G 0 Y = EDG Reaction progress
Amine Salts • Ionic solids with high melting points • Soluble in water • No fishy odor =>
Separation and purification of amine component from a mixture Amine + neutral compound Dissolve in ether, add aq. HCl Ether layer (neutral compound) Aqueous layer (RNH 3+Cl-; amine salt) Add Na. OH, ether Ether layer (amine) Aqueous layer (Na. Cl)
Preparation of amines SN 2 reaction of alkyl halides
Preparation of amines Azide synthesis (SN 2 reaction)
Preparation of amines Gabriel synthesis (SN 2 reaction) benzylamine
Preparation of amines Reduction of nitriles and amides
Preparation of amines Reductive amination of ketones and aldehydes
Preparation of amines Reductive amination of ketones and aldehydes Primary amine Secondary amine Tertiary amine
Preparation of amines Hofmann rearrangement
Preparation of amines Curtius rearrangement azide
Preparation of arylamines Two-step sequence: nitration, reduction 90% yield
Reactions of amines Alkylation
Reactions of amines Acylation (with acid chlorides, anhydrides or esters) Tertiary amines do not react with carboxylic acids derivatives
Reactions of amines Hofmann elimination
Reactions of amines Reaction of alkylamines with nitrous acid Unstable, decomposes immediately after formation with evolution of nitrogen gas
Reactions of arylamines Reaction of arylamines with nitrous acid (diazotization) Primary arylamine Arenediazonium salt Stable < 5 C
Reactions of arylamines Diazonio replacement reactions Cu. Br Na. I -N 2 Cu. Cl Cu. CN -N 2 H 3 O+ heating H 3 PO 2 -N 2
Reactions of arylamines Diazonium coupling reactions An azo compound Where Y = -OH (phenol) or -NR 2 (tertiary arylamine) Y – strong electron donating group
Reactions of arylamines Example of diazonium coupling reactions
Quaternary ammonium salts in Phase Transfer Catalysis
Quaternary ammonium salts in Phase Transfer Catalysis How it works? R 4 N+ Cl. Aqueous phase Organic phase H 2 O + Na+ HO- + Cl+ R 4 N+ CHCl 3 + cyclohexene + R 4 N+ HO-
Quaternary ammonium salts in Phase Transfer Catalysis Examples:
Naturally Occurring Amines Alkaloids Cinchona flower Quinine (antimalarial)
Naturally Occurring Amines Alkaloids Reserpine (antihypertensive) Rauwolfia serpentina
Naturally Occurring Amines Alkaloids Morphine (an analgesic) Papaver somniferum
Morphine Alkaloids Heroin – not found in nature
Morphine derivatives Codeine – found in nature (analgesic, antitussive) Nalorphine – synthetic analgesic, morphine antagonist
„Morphine Rule” (Structural requirements necessary for biological activity) Quaternary carbon linked to phenyl ring, and two carbon chain bonded to tertiary amino group QSAR –quantitative structure-activity relationship
Synthetic analgesics Meperidine - pain killer
Synthetic analgesics Methadone - treatment of heroin addiction
Opioid receptors μ receptor Opioid receptor with antagonist molecule
- Secondary amine
- Amines chemsheets
- Aliphatic amines and aromatic amines
- Guanidine basicity
- Wastewater treatment process primary secondary tertiary
- Primary secondary tertiary colors
- Carboxylic acid to tertiary alcohol
- Primary secondary tertiary sources
- Primary secondary and tertiary protein structure
- Levels of care primary secondary tertiary quaternary
- Clouds
- Least cost theory
- What is primary processing
- Education level primary secondary tertiary malaysia
- Primary secondary and tertiary sector
- 4 levels of economic activity
- Primary and secondary activities
- Sector in business
- Cis-1-tert-butyl-3-methylcyclohexane
- Sewage treatment primary secondary and tertiary
- Three peptide chains woven like a rope
- Primary secondary and tertiary protein structure
- Respiratory membrane
- Physiology of respiration
- Parietal pleura
- Tertiary industries
- Is fishing primary secondary or tertiary
- Primary prevention secondary prevention tertiary prevention
- Primary secondary tertiary
- Primary secondary and tertiary structure of protein
- Amine group ir spectrum
- Atropine tertiary amine
- Amine group
- Primary and secondary activities
- Primary amine structure
- Primary amine and nitrous acid
- Vital + amine
- Physical properties of amines
- Les polyacides
- Amine vasoactive
- Naming amine
- Chapter 20
- Amines hydrogen bonding
- Reaction of amines with carboxylic acid
- Chromotagraphie
- Ch3 nh ch ch3 twice
- Are amines water soluble
- Solubility of amines
- Basicity amines
- Do aromatic amines give hinsberg test
- Benzoylation reaction of amines
- Basic character of amines
- Adrenergic agonist