LECTURE NOTE SK025 (ORGANIC) KMKt

ANSWER:

CH3 CH2 CH2 OH SOCl2 CH3 CH2 CH2 Cl excess NH3 CH3 CH2 CH2 NH2
pyridine Δ

CH3COOH
Δ

O
CH3 C NH CH2CH2CH3

Edited By: Revised By:
SEJ/ZS MS

Approved By:
ZA

CHAPTER 12

AMINO ACIDS
12.1 Introduction to Amino Acids
12.2 Chemical Properties

Learning Outcomes

12. : INTRODUCTION TO AMINO ACIDS 2

Students should be able to:

a) Give the name for a given amino acid according to the
IUPAC nomenclature (C2)

b) Give the general structure of α-amino acid in 12.1(a). (C2)
c) Define the terms:

i. zwitterion;
ii. Isoelectric point (pI). (C1)
d) Predict the structure of a given amino acid,
i. in acidic medium
ii. in basic medium
iii. at pI. (C3)

12.1 : INTRODUCTION TO AMINO ACIDS

amino acid

amino group carboxyl group
-NH2 -COOH

Amino acids are molecules with two functional groups:
Amino group (-NH2) and Carboxyl group (-COOH)

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Amino acid commonly found in proteins are -amino acid

-amino
acid?

Acid amino on which both
carboxyl and amino

groups are bonded to the
SAME CARBON atom.

General structure of -amino acid

Amino H2N HO Carboxyl
group C C-OH group
R  carbon
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Classification of 20 Amino Acids in Protein.

Name Structure

Glycine H CH COOH
(Gly)
NH2
Alanine H3C CH COOH
(Ala)
NH2

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Valine CH3 COOH
(Val) HC CH

Leucine CH3 NH2
(Leu)
CH3
Isoleucine
(Ile) CHCH2 CH COOH

CH3 NH2

CH3CH2CH CH COOH
CH3 NH2

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Phenylalanine CH2 CH COOH
(Phe) NH2

Tryptophan O
(Trp)
OH
NH NH2

Proline CH2 CH2 COOH
(Pro) H
C
CH2 NH

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Serine HO CH2 CH COOH
(Ser) NH2

Threonine OH
(Thr) CH3 C CH COOH

Cysteine H NH2
(Cys)
HS CH2 CH COOH
NH2

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Methionine CH3 S CH2CH2 CH COOH
(Met) NH2

Tyrosine HO CH2 CH COOH
(Tyr) NH2

Asparagine NH2 C CH2 CH COOH
(Asn)
O NH2

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Glutamine NH2 C CH2CH2 CH COOH

(Gln) O NH2

Aspartic acid HOOC CH2 CH COOH

(Asp) NH2

Glutamic acid HOOC CH2CH2 CH COOH

(Glu) NH2

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Lysine H2N CH2CH2CH2CH2 CH COOH
(Lys)
NH2

Arginine H2N C NH CH2CH2CH2 CH COOH
(Arg)
NH NH2

HC C CH2 CH COOH
N NH NH2
Histidine
(His) CH

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❖ Amino acids with an additional COOH group in the side chain -
acidic amino acids

❖ Amino acids with an additional N atom in the side chain -
basic amino acids

❖ Others are neutral amino acids H

H basic H2N C COOH
CH2—COOH
H2N C COOH H
CH acidic
H2N C COOH
CH3 CH3
CH2—CH2—CH2—CH2—NH2
neutral

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Nomenclature

❑ The names of -amino acids given are common names.
❑ In IUPAC nomenclature, -amino acids are named as carboxyl group

as the parent name whereas amino group as substituent group.
❑ However, IUPAC names are not normally used for -amino acids

O O
H-CH-C CH3-CH-C

OH OH
NH2 NH2

aminoethanoic acid 2-aminopropanoic acid
(alanine)
(glycine)

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HOW TO NAME THESE AMINO ACID BASED ON
IUPAC NOMENCLATURE?

a) glycine H

H2N C COOH
H

aminoacetic acid / aminoethanoic acid

b) alanine H

H2N C2 1

COOH

3 CH3

2–aminopropanoic acid 14

HOW TO NAME THESE AMINO ACID BASED ON

IUPAC NOMENCLATURE?

H

c) valine H2N C2 1

COOH

H C3 C4H3

CH3

2–amino–3–methylbutanoic acid

d) isoleucine H

H2N C2 1

COOH

CH3—C3H—C4H2C5H3

2–amino–3–methypentanoic acid 15

Physical Properties

❑ Amino acids are white crystalline solids with high melting
points.

❑ Amino acids such as glycine and alanine dissolve in water
to form neutral solution but have low solubility in organic
solvents.

This unique properties :

➢ High melting points
➢ High solubility in water (but low solubility in organic solvents)

indicates that amino acids exists as polar ions.

-Amino acids are dipolar ions. The term used for dipolar ion is zwitterion .

Dipolar ions = zwitterion

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Zwitterion

❑ Zwitterion is a molecule with an overall charge of zero which has a

positive charge at one part and a negative charge group at another.
❑ In neutral solution and in solid state, amino acids exist as zwitterion.
❑ A zwitterion formed when a proton from the –COOH group is donated to

the –NH2 group of the same molecule.

O O

R-CH-C R-CH-C
O-H NH3+ O-

NH2 Zwitterion (dipolar ion)

Uncharge structure

However, the molecules has no net charge 17

Neutral amino acids are amphoteric.
It can react as acid or base depending on the pH of the solution.

In Acidic O In Basic
H-CH-C
Solution H+ OH- Solution
O-
O NH3+ O
H-CH-C H-CH-C
Zwitterion
OH (neutral) O-
NH3+ NH2
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cation anion
(acid, pH low) (base, pH high)

Amino acids can exists in 3 forms depending on the pH of the solution.

In ACIDIC In NEUTRAL In BASIC

Cations are Zwitterions are Anions are
predominates predominates predominates

O O O
H-CH-C H-CH-C H-CH-C

OH O- O-
NH3+ NH3+ NH2

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Isoelectric point, pI

❑ The pH whereby the concentration of zwitterion is at maximum and there is
equal concentration of both anion and cation.

❑ At pI, zwitterion has no net charge.

➢ Each amino acids has its own specific pI.
➢ For example: ALANINE

✓ Isoelectric point for Alanine is at pH 6.02
✓ At this pH, alanine exist as zwitterion

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Example :

The isoelectric point of valine, 2-amino-3-methylbutanoic acid is 6.0. Predict
the structural formula of valine at

a) Isoelectric point, pI (pH 6) c) pH 1
H3N+ –CH–COO– +
CH(CH3)2
H3N–CH–COOH
CH(CH3)2

b) pH 12
H2N–CH–COO–
CH(CH3)2

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PAST YEARS QUESTIONS

Isoleucine, 2-amino-3-methylpentanoic acid is a -amino acid. Its isoelectric
point is 6.0. Draw the structural formula of isoleucine at pH 1.0, pH 6.0 and pH
10.0.

PROBLEM SOLVING:

CH3 O pH 6.0 – Isoelectric point
– zwitterion (neutral)
CH3-CH2-CH-CH-C OH
pH 1.0 – acidic solution

pH 10.0 – basic solution

NH2

2-amino-3-methylpentanoic
acid

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PROBLEM SOLVING:

H+ Zwitterion OH-

Acidic pH 6.0

pH 1.0 CH3 O
CH3-CH2-CH-CH-C O-

Basic NH2

pH 10.0

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Learning Outcomes

12.2 : CHEMICAL PROPERTIES

Students should be able to:

a) Explain the reaction of Amino Acid with:
i. hydrochloric acid
ii. sodium hydroxide
iii. nitrous acid
iv. alcohols in the presence of an acid catalyst. (C3)

b) Explain the formation of peptide bond in dipeptides. (C3)

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12.2 : CHEMICAL PROPERTIES

Since amino acid have both acidic (–COOH) and basic (–NH2) functional

group, amino acids will undergo 2 main types of chemical reactions:

1. Reactions characteristic of the amino group

 Reaction with HCl
 Reaction with nitrous acid (HNO2)

2. Reactions characteristic of the carboxyl group

 Reaction with NaOH
 Reaction with alcohols in the presence of an acid catalyst (esterification)

Reaction of Amino group (-NH2)

1 Reaction with HCl

Amino group is basic, so it react with HCl to form salt.
General Equation:

O + HCl O

R-CH-C R-CH-C
OH OH

NH2 NH3+Cl-

Amino acid Acidic salt

Example:
Reaction Of Alanine With HCl

O O
CH3-CH-C
CH3-CH-C OH + HCl
OH
NH2 NH3+Cl-

Alanine

2 Reaction with Nitrous Acid (HNO2)

Nitrous acid are prepared in situ from NaNO2 + HCl

Amino group react with HNO2 at 0oC to form diazonium salt as

intermediate product

This salt decompose easily by losing N2 to form carbocation.

The carbocation react with nucleophile to form a mixture

of products such as alcohol, alkene, haloalkanes and HCl

Same reaction that we
learn in 1o aliphatic

amine with nitrous acid

General Equation:

H NaNO2,HCl H
R–C–COOH (below 0oC) R–C–COOH + H2O
Nitrous acid
NH2 +N≡NCl-
Amino acid Diazonium salt

H N2 
R–C+–COOH
Carbocation

H H H + HCl
R=C–COOH
R–C–COOH R–C–COOH
Cl + OH +

Example: Alanine NaNO2,HCl O Diazonium
O (below 0oC) salt
CH3-CH-C OH
CH3-CH-C +N≡N-Cl-
OH

NH2
Alanine

2-hydroxypropanoic CH3-CH-COOH N2 
acid OH
+ CH3-C+H-COOH
Carbocation
Propenoic acid CH2=CH-COOH
+

CH3-CH-COOH
2-chloropropanoic acid Cl

+

HCl

Reaction of Carboxyl group (-COOH)

3 Reaction with Sodium Hydroxide (NaOH)

Carboxyl group is acidic, so it react with NaOH to form salt.
General equation:

O O
H-CH-C + NaOH
H-CH-C + H2O
OH
NH2 NH2 O-Na+

Amino acid Basic salt

Example:
Reaction Of Alanine With NaOH

O O
CH3-CH-C O-Na+ + H2O
CH3-CH-C + NaOH
NH2
NH2 OH
sodium 2-aminopropanoic acid
2-aminopropanoic acid

4 Reaction with Alcohol (esterification)

Amino acid reacts with alcohol in presence of an acid (normally HCl/H2SO4)
as a catalyst to form ester and water
General equation:

O H+ O

R-CH-C + R-OH R-CH-C + H2O
OH
O-R
NH2 NH3+
Amino acid
ester

Example:
Alanine reacts with methanol in presence of HCl

O + CH3OH H+ O + H2O
methanol  CH3-CH-C
CH3-CH-C
OH NH3+ O-CH3

NH2 ester

2-aminopropanoic acid

Formation Of Peptide Bonds

Peptide bond is a linkage between two amino acid residue.
When 2 amino acids react together, H2O is eliminated, and a compound
formed is known as dipeptide

+

NOTES: Peptide + H2O
N- terminal (with free bond
dipeptide
–NH2) is always
written on left side
and C-terminal (with
free –COOH) on right

side

HO HO
H-N-CH-C OH
+ H N-CH-C-OH
R R

condensation

HO H OH O HO

H-N-CH-C N-CH-C N-CH-C N-CH-C-OH
N-terminal R R R R C-terminal

Peptide bonds + H2O

polipeptide

2 amino acids = dipeptide

3 amino acids = tripeptide

15-30 amino acids = oligopeptide

> 30 amino acids = polipeptide

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Example: Formation of two dipeptides from glycine (Gly) and alanine (Ala)
The name of the dipeptides are glycylalanine (Gly-Ala) and alanylglycine (Ala-Gly)

HO HO

H-N-CH-C-OH + H-N-CH-C-OH

H CH3

Glycine Alanine

H OH O

H-N-CH-C N-CH-C-OH + H2O
H CH3

Peptide bonds Gly-Ala

HO + HO
H-N-CH-C-OH
H-N-CH-C-OH
CH3 H

Alanine Glycine

+ H2O

Ala-Gly Peptide bonds

Exercise:

(a) The structure of alanine is given as below:

Draw the structure of alanine as zwitterion. [1 mark]
(b) Reaction of valine with several reagents are shown below:

Draw the structures of products AA, BB and CC. [3 marks]

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ZS, MNMD, SEJ, AAI MS

ZA

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