Amines & Amino Acids

Nitrogen-containing organic compounds: amines are derivatives of ammonia, while amino acids are the building blocks of proteins containing both amino and carboxyl groups.

Amines (RNH₂, R₂NH, R₃N)

Classification

Type	Formula	Example
Primary (1°)	RNH₂	Methylamine (CH₃NH₂)
Secondary (2°)	R₂NH	Dimethylamine ((CH₃)₂NH)
Tertiary (3°)	R₃N	Trimethylamine ((CH₃)₃N)
Quaternary (4°)	R₄N⁺X⁻	Tetramethylammonium chloride

CN
CNC
CN(C)C
Nc1ccccc1
C[N+](C)(C)C

Type	Example	SMILES
Primary amine	Methylamine	`CN`
Secondary amine	Dimethylamine	`CNC`
Tertiary amine	Trimethylamine	`CN(C)C`
Aromatic amine	Aniline	`Nc1ccccc1`
Quaternary ammonium	Tetramethylammonium	`C[N+](C)(C)C`

Nomenclature

Prefix: amino- or suffix: -amine
Examples: ethylamine, aniline (phenylamine), diethylamine

Physical Properties

Hydrogen bonding (1° and 2° only)
Lower boiling points than comparable alcohols (N-H weaker than O-H)
Fishy/amine odor

Basicity

Amines are basic due to the lone pair on nitrogen:

Aliphatic: R-NH₂ + H₂O ⇌ R-NH₃⁺ + OH⁻
Aromatic (aniline): Less basic (lone pair delocalized into ring)

Basicity order: Aliphatic 2° > Aliphatic 3° > Aliphatic 1° > NH₃ > Aromatic

Preparation

1. Reduction of Nitro Compounds (R-NO₂ → R-NH₂)

Reagents: H₂/Ni, Pt, or Pd; Zn/Fe/Sn + HCl; SnCl₂ + HCl; LiAlH₄ + hydrolysis.

N(=O)(=O)c1ccccc1>>Nc1ccccc1

Nitrobenzene → Aniline

2. Reduction of Amides (R-CONH₂ → R-CH₂NH₂)

Reagents: H₂/Ni, Pt, or Pd; LiAlH₄ + hydrolysis. The carbonyl carbon is reduced to CH₂; carbon count stays the same.

CC(N)=O>>CCN

Ethanamide → Ethanamine

3. Reduction of Nitriles (R-CN → R-CH₂NH₂)

Reagents: H₂/Ni, Pt, or Pd; LiAlH₄ + hydrolysis. Produces primary amines only; carbon count increases by 1.

CC(C)C#N>>CC(C)CN

2-methylpropanenitrile → 2-methylpropan-1-amine

4. Hoffmann Degradation of Amides

Primary amide + halogen (Cl₂ or Br₂) + strong base (NaOH/KOH) → primary amine with one carbon removed.

NC(=O)c1ccccc1>>Nc1ccccc1

Benzamide → Aniline (loses C=O carbon)

5. Alkylation of Ammonia

NH₃ + R-X → mixture of 1°, 2°, 3° amines + quaternary salts. This is a poor method due to multiple alkylations.

N.CCCl>>CCN

Ammonia + chloroethane → ethylamine (plus further alkylated products)

Reactions

1. Alkylation

Formation of higher order amines and quaternary ammonium salts via nucleophilic substitution.

2. Acylation (Amide Formation)

Amines react with acid chlorides, acid anhydrides, and esters to form amides.

With acid chlorides:

CC(=O)Cl.CN>>CC(=O)NC

Acetyl chloride + methanamine → N-methylacetamide

[!note] 3° amine limitation Tertiary amines do not react with acid chlorides (no N-H proton to transfer to Cl).

With acid anhydrides:

CC(=O)OC(C)=O.CN>>CC(=O)NC

Acetic anhydride + methanamine → N-methylacetamide + acetic acid

With esters:

COC(C)=O.CCN>>CCNC(C)=O

Methyl acetate + ethanamine → N-ethylacetamide + methanol

3. Reaction with Nitrous Acid (HNO₂)

Nitrous acid is prepared in situ (HCl/NaNO₂ or H₂SO₄/NaNO₂). Different amine classes give different products — used as a distinguishing test.

Amine class	Product	Observation
1° aliphatic	Unstable diazonium salt → N₂ + carbocation → mixture of alkene, alcohol, haloalkane	Bubbles of N₂ gas
1° aromatic	Stable arenediazonium salt (< 5 °C)	No gas at < 5 °C
2° aliphatic & aromatic	N-nitrosamine	Yellow oil
3° aliphatic	Mixture of trialkylammonium chloride + trialkylnitrosoammonium chloride	Clear solution
3° aromatic	C-nitrosation at para position (or ortho if para blocked)	Solid precipitate

Primary aliphatic — N₂ evolution:

CCCN.O=N[O-].[Na+].[Cl-].[Na+].Cl>>C=CC

Propan-1-amine → propene + propan-2-ol + 2-chloropropane + N₂

Primary aromatic — diazonium salts:

Nc1ccccc1.O=N[O-].[Na+].[Cl-].[Na+].Cl>>[N+]#Nc1ccccc1.[Cl-]

Aniline → benzenediazonium chloride

Arenediazonium salts are versatile intermediates. The diazonium group can be replaced by various nucleophiles:

Reagent	Product
H₃O⁺	Phenol
CuCl	Chlorobenzene
CuBr	Bromobenzene
CuCN	Benzonitrile
KI	Iodobenzene

Azo coupling:

[Cl-].[N+]#Nc1ccccc1.Oc1ccccc1>>O=S(=O)([O-])c1ccc(N=Nc2ccccc2O)cc1

Benzenediazonium salt + phenol → orange azo dye

Secondary amines — yellow oil:

CNC.O=N[O-].[Na+].[Cl-].[Na+].Cl>>CN(C)N=O

Dimethylamine → N,N-dimethylnitrous amide (yellow oil)

Tertiary aromatic — C-nitrosation:

CN(CC)c1ccccc1.O=N[O-].[Na+].[Cl-].[Na+].Cl>>CN(CC)c1ccc(N=O)cc1

N-ethyl-N-methylaniline → N-ethyl-N-methyl-4-nitrosoaniline (solid)

4. Reaction with Bromine Water

Aniline reacts vigorously with aqueous bromine to form 2,4,6-tribromoaniline (white precipitate). The amino group is strongly activating and ortho-para directing.

Nc1ccccc1.[Br-].[Br-].[Br-].[K+].[K+].[K+]>>Nc1c(Br)cc(Br)cc1Br

Aniline + 3 Br₂(aq) → 2,4,6-tribromoaniline (white precipitate) + 3 HBr

[!tip] Preliminary test This reaction is used as a preliminary test for aniline due to the clear observation (brown bromine decolorizes + white precipitate forms).

5. Hinsberg Test

Distinguishes 1°, 2°, and 3° amines using benzenesulfonyl chloride.

6. Electrophilic Aromatic Substitution

Amino group is strongly activating and ortho-para directing.

Amino Acids (H₂N-CHR-COOH)

Structure

α-carbon bonded to: amino group, carboxyl group, hydrogen, and side chain (R)
Chiral (except glycine, R=H)
L-configuration in natural proteins

The 20 Common Amino Acids

Non-polar / Hydrophobic

Glycine (Gly, G) — non-essential

NCC(=O)O

Side chain: H | Functional group: none

Alanine (Ala, A) — non-essential

CC(N)C(=O)O

Side chain: -CH₃ | Functional group: alkyl

Valine (Val, V) — essential

CC(C)C(N)C(=O)O

Side chain: -CH(CH₃)₂ | Functional group: alkyl

Leucine (Leu, L) — essential

CC(C)CC(N)C(=O)O

Side chain: -CH₂-CH(CH₃)₂ | Functional group: alkyl

Isoleucine (Ile, I) — essential

CCC(C)C(N)C(=O)O

Side chain: -CH(CH₃)-CH₂-CH₃ | Functional group: alkyl

Phenylalanine (Phe, F) — essential

NC(Cc1ccccc1)C(=O)O

Side chain: -CH₂-C₆H₅ | Functional group: aromatic

Proline (Pro, P) — non-essential

O=C(O)C1CCCN1

Side chain: cyclic -CH₂-CH₂-CH₂- | Functional group: rigid cyclic

Methionine (Met, M) — essential

CSCCC(N)C(=O)O

Side chain: -CH₂-CH₂-S-CH₃ | Functional group: sulfide

Tryptophan (Trp, W) — essential

NC(Cc1c[nH]c2ccccc12)C(=O)O

Side chain: -CH₂-indole | Functional group: indole

Polar Uncharged

Serine (Ser, S) — non-essential

NC(CO)C(=O)O

Side chain: -CH₂-OH | Functional group: hydroxyl

Threonine (Thr, T) — essential

CC(O)C(N)C(=O)O

Side chain: -CH(OH)-CH₃ | Functional group: hydroxyl

Tyrosine (Tyr, Y) — non-essential

NC(Cc1ccc(O)cc1)C(=O)O

Side chain: -CH₂-C₆H₄-OH | Functional group: phenolic —OH

Cysteine (Cys, C) — non-essential

NC(CS)C(=O)O

Side chain: -CH₂-SH | Functional group: thiol

Asparagine (Asn, N) — non-essential

NC(=O)CC(N)C(=O)O

Side chain: -CH₂-CONH₂ | Functional group: amide

Glutamine (Gln, Q) — non-essential

NC(=O)CCC(N)C(=O)O

Side chain: -CH₂-CH₂-CONH₂ | Functional group: amide

Acidic (Negatively charged at pH 7)

Aspartic acid (Asp, D) — non-essential

NC(CC(=O)O)C(=O)O

Side chain: -CH₂-COOH | Functional group: carboxylic acid

Glutamic acid (Glu, E) — non-essential

NC(CCC(=O)O)C(=O)O

Side chain: -CH₂-CH₂-COOH | Functional group: carboxylic acid

Basic (Positively charged at pH 7)

Lysine (Lys, K) — essential

NCCCCC(N)C(=O)O

Side chain: -(CH₂)₄-NH₂ | Functional group: amino

Arginine (Arg, R) — essential

NC(CCCNC(=N)N)C(=O)O

Side chain: -(CH₂)₃-NH-C(=NH)-NH₂ | Functional group: guanidino

Histidine (His, H) — essential

NC(Cc1c[nH]cn1)C(=O)O

Side chain: -CH₂-imidazole | Functional group: imidazole

[!note] Essential Amino Acids Ten amino acids must be obtained from diet (body cannot synthesize): Arg, Thr, Lys, Val, Phe, Trp, Met, His, Leu, Ile.

Classification

Amino acids can be classified in several ways:

By structure: Based on core functional groups' locations (α-, β-, γ-carbon, etc.)
By polarity: Grouped by functional groups in the side chain
By pH level: Acidic (Asp, Glu), Basic (Lys, Arg, His), Neutral (Gly, Ala, etc.)
By nutritional importance:
- Essential: Must be obtained from diet
- Semi-essential: Required during specific conditions
- Non-essential: Synthesized by the body

Nomenclature

Named as derivatives of carboxylic acids
The carboxyl (-COOH) group is the parent chain (highest priority)
All other groups (amino, sulfides, hydroxyl) are named as substituents
Examples:
- Methionine: 2-amino-4-methylthiobutanoic acid
- Asparagine: 2,4-diamino-4-oxobutanoic acid

Physical Properties

Crystalline solids with high melting points — strong ionic attractions between zwitterions require more energy to break
Solubility in water — generally soluble; insoluble in non-polar solvents (hydrocarbons); solubility varies based on R-group nature
Highly polar molecules — large dipole moment; high dielectric constant

Chemical Reactions

Reactions of the Carboxylic Acid Group

With NaOH: Neutralization forming salt and water
With alcohol (Esterification): Ester formed when amino acid and alcohol are warmed in presence of acid (HCl/H⁺)

Reactions of the Amino Group

With HCl: Forms aminium salt
With acid chlorides: Formation of acyl derivatives
With nitrous acid (HNO₂) at 0°C: Formation of α-hydroxy carboxylic acids; products include alcohols, haloalkanes, and alkenes

Zwitterions

At neutral pH:

Amino group protonated: -NH₃⁺
Carboxyl group deprotonated: -COO⁻
Net charge = 0, but dipolar
Amino acids NEVER exist as uncharged molecules
In solid form, they exist as zwitterions with strong electrostatic attraction causing high melting points

Isoelectric Point (pI)

The pH at which the amino acid has zero net charge:

Neutral side chains: pI = ½(pKa₁ + pKa₂)
Acidic side chains: pI = average of the two most acidic pKa values
Basic side chains: pI = average of the two least acidic pKa values

pKa Values:

Carboxyl group (-COOH): pKa ≈ 2 (stronger acid)
Amino group (-NH₃⁺): pKa ≈ 9–10 (weaker acid)
Example titration: glycine pKa₁ ≈ 2.3, pKa₂ ≈ 9.6, pI = 6.0
Example: Lysine pI = (10.53 + 8.95)/2 = 9.74
Neutral amino acids have isoelectric pH slightly acidic (5–6)
Amino acids are least soluble at pI

Electrophoresis

At pH < pI: Net positive → moves toward cathode (-)
At pH > pI: Net negative → moves toward anode (+)
At pH = pI: No movement
A mixture of amino acids can be separated on a buffered medium; when voltage is applied, movement depends on pI relative to solution pH

Peptides and Proteins

Peptide Bond

Amide linkage: -CO-NH-
Formed by condensation between carboxyl of one amino acid and amino of another
Planar (partial double bond character)
Usually trans configuration

Protein Structure

Level	Description	Bonds/Forces
Primary	Amino acid sequence	Peptide bonds
Secondary	α-helix, β-sheet	Hydrogen bonds
Tertiary	3D folding	Disulfide, H-bonds, ionic, hydrophobic
Quaternary	Multiple subunits	Same as tertiary

Sources

FAD1018 W12 — Amine & Amino Acids
FAD1018 - Basic Chemistry II

Amines & Amino Acids

Amines (RNH₂, R₂NH, R₃N)

Classification

Nomenclature

Physical Properties

Basicity

Preparation

1. Reduction of Nitro Compounds (R-NO₂ → R-NH₂)

2. Reduction of Amides (R-CONH₂ → R-CH₂NH₂)

3. Reduction of Nitriles (R-CN → R-CH₂NH₂)

4. Hoffmann Degradation of Amides

5. Alkylation of Ammonia

Reactions

1. Alkylation

2. Acylation (Amide Formation)

3. Reaction with Nitrous Acid (HNO₂)

4. Reaction with Bromine Water

5. Hinsberg Test

6. Electrophilic Aromatic Substitution

Amino Acids (H₂N-CHR-COOH)

Structure

The 20 Common Amino Acids

Non-polar / Hydrophobic

Polar Uncharged

Acidic (Negatively charged at pH 7)

Basic (Positively charged at pH 7)

Classification

Nomenclature

Physical Properties

Chemical Reactions

Reactions of the Carboxylic Acid Group

Reactions of the Amino Group

Zwitterions

Isoelectric Point (pI)

Electrophoresis

Peptides and Proteins

Peptide Bond

Protein Structure

Related Topics

Sources