VJC 2025 Organic Compounds Notes

1 VICTORIA JUNIOR COLLEGE CHEMISTRY DEPARTMENT Tan Kuang Shing (tan.kuang.shing@vjc.edu.sg) ORGANIC NITROGEN COMPOUNDS [H2 only] SLS Lessons 1 2 3 Topics Amines Amides Amino Acids & Proteins Pages 1 - 14 15 - 23 24 – 31 Tutorial Q 1 2 – 6 7 – 9 LESSON OUTLINE PART I: AMINES 1 Classes of Amines 2 Nomenclature of Amines 3 Properties of Aliphatic Amines 4 Properties of Phenylamine 5 Basicity of Amines 6 Preparation of Aliphatic Amines 6 .1 Nucleophilic Substitution of Halogenoalkanes 6 .2 Reduction of Amides 6.3 Reduction of Nitriles 7 Preparation of Phenylamine by Reduction of Nitrobenzene 8 Reactions of Aliphatic Amines and Phenylamine 8 .1 Neutralisation 8 .2 Nucleophilic Substitution of Halogenoalkanes 8 .3 Condensation Reaction with Acyl Chloride 9 Electrophilic Substitution of Phenylamine PART II: AMIDES 1. Classes of Amides 2. Nomenclature of Amides 3. Properties of Amides 4. Preparation of Amides by Condensation Reaction between Amines and Acyl Chlorides 5. Reactions of Amides 5 .1 Acid Hydrolysis 5 .2 Base Hydrolysis 5 .3 Reduction PART III: AMINO ACIDS AND PROTEINS 1. Structure and Nomenclature 2. Classification of Amino Acids 3. Acid-Base Nature of Amino Acids 3.1. Formation of Zwitterions and their Physical Properties 3.2. Acid-Base Properties 3.2.1 Titration Curve of a Fully Protonated Neutral Amino Acid, Glycine H 3N+CH2CO2H 3.2.2 Titration Curve of a Fully Protonated Acidic Amino Acid, Glutamic Acid H3N+CH(CH2CH2CO2H)CO2H 3.2.3 Titration Curve of a Fully Protonated Basic Amino Acid, Lysine H3N+CH(CH2(CH2)3NH3+)CO2H 4. Peptide (Amide) Bonds Formation 4.1 Condensation Reaction between Amino Acids 4.2 Properties of a Peptide (Amide) Bond 5. Formation of Proteins 6. Hydrolysis of Proteins 6.1 Acid-Base Catalysed Hydrolysis 6.2 Enzymatic Hydrolysis

2 ASSESSMENT OBJECTIVES (a) D escribe the formation of amines as exemplified by ethylamine (through amide and nitrile reduction) and by phenylamine (through the reduction of nitrobenzene) (b) Describe the reaction of amines in the formation of salts (c) Describe and explain the basicity of primary, secondary and tertiary amines in the gaseous phase (interpret as Lewis bases) (d) E xplain the relative basicities of ammonia, ethylamine and phenylamine in aqueous medium, in terms of their structures (e) Describe the reaction of phenylamine with aqueous bromine (f) D escribe the formation of amides from the condensation reaction between RNH 2 and R'COCl (g) Explain why an amide is neutral in terms of delocalisation of the lone pair of electrons on nitrogen (h) Describe the chemistry of amides, exemplified by the following reactions: (i) h ydrolysis on treatment with aqueous alkali or acid (ii) reduction to amines with lithium aluminium hydride (i) Describe the acid/base properties of amino acids and the formation of zwitterions (j) Describe the formation of peptide (amide) bonds between α -amino acids, and hence explain protein formation (k) Describe the hydrolysis of proteins REFERENCES 1 Introduction to Organic Chemistry by GI Brown 2 Principles of Organic Chemistry by Peter RS Murray 3 Organic Chemistry by Morrison and Boyd 4 Organic Chemistry by TW Graham Solomons

3 PART I: AMINES 1 Classes of Amines  Amines are derivatives of NH3. They are formed by replacing one or more hydrogen atoms by a substituent such as an alkyl or aryl group.  Amines are classified into 4 groups. • Primary amines, R NH2, have one hydrogen atom in ammonia replaced by a substituent. • Secondary amines, R2NH, have two hydrogen atoms in ammonia replaced by substituents. The two R groups can be the same or different. • Tertiary amines, R3N, have all three hydrogen atoms in ammonia replaced by substituents. The three R groups can be the same or different. • Quaternary ammonium cations, R4N+, are cations with four substituents bonded to N. The four R groups can be the same or different. N R H H N R R H N R R R N R R R R + 1o amine 2o amine 3o amine 4o ammonium ion 2 Nomenclature of Amines  Aliphatic amines are named as ‘alkylamine’  A romatic amines are named as ‘phenylamine’  Quaternary ammonium cations are named as ‘alkylammonium’ cations  As substituents, amines are known as ‘amino’  Examples Formula Name Classification CH3CH2NH2 primary CH3CH2NHCH3 Ethylmethylamine [substituents are arranged in alphabetical order] (CH3CH2)3N tertiary (CH3)4N+Cl– tetramethylammonium chloride NH2 primary CH3(CH2)3CH(NH2)CH3 2–aminohexane H2NCH2CH2CO2H primary

4 3 Properties of Aliphatic Amines Note: When comparing the boiling points of two compounds, other than the different types of intermolecular forces of attraction, it is also important to consider their relative molecular mass or molar mass. Mr or M is an indicator of the number of electrons in a molecule. A molecule with higher Mr or M has more electrons. This will lead to higher boiling points due to stronger intermolecular instantaneous dipole – induced dipole f orces of attraction (id-id) holding the molecules in the liquid together.  Aliphatic amines have higher boiling points than hydrocarbons of comparable mass due to their ability to form intermolecular hydrogen bonds in addition to id-id interactons between the non-polar alkyl groups, whereas there are only id- id interactions between non–polar hydrocarbon molecules. Hence more energy is needed to separate amine molecules. CH3CH2CH3 (propane) Mr = 44 b.p. = –42 °C CH3CH2NH2 (ethylamine) Mr = 45 b.p. = 16.6 °C  Aliphatic amines have lower boiling points than alcohols of comparable mass. While the no. of hydrogen bonds per molecule is the same, the N–H bonds are less polar than O–H bonds since N is less electronegative than O. As such, the hydrogen bonds between amine molecules are weaker than those between alcohol molecules. CH3CH2NH2 (ethylamine) Mr = 45 b.p. = 16.6 °C CH3CH2OH (ethanol) Mr = 46 b.p. = 78.5 °C  Aliphatic amines are soluble in water as they can form hydrogen bonds with water molecules. Energy released can overcome the interactions between amine molecules ( hydrogen bonds and id -id interations) and the hydrogen bonds between water molecules. However, solubility decreases with the increase in the number of carbon atoms in the R group due to increasing strength of id-id interactions between the non-polar hydrocarbon (alkyl) chains as number of electrons in the molecule increass, and so more energy is needed to overcome the attractions between the amine molecules , leading to lower solubility. 4 Properties of Phenylamine  Phenylamine, also known as aniline or aminobenzene, is an aromatic primary amine. Pure phenylamine is a colourless liquid, but it darkens rapidly on exposure to light and air. It is normally a brown oily liquid.  Phenylamine and methylbenzene contain similar number of electrons but phenylamine has a higher boiling point than methylbenzene. This is due to its ability to form hydrogen bonds between the amine groups in addition to id-id interactions between the non-polar rings. There are only id- id interactions between non– polar methylbenzene molecules. Hence more energy is needed to separate phenylamine molecules. Mr melting point / °C boiling point / °C C6H5NH2 93 –6.2 184 C6H5CH3 92 –95 111 N R R H δ+ δ− N H R R δ− δ+ δ+ δ− δ− δ+ R O H H O R δ+ δ+ N H R H δ− δ+ δ−H O H δ+ hydrogen bond hydrogen bond hydrogen bond

5  Phenylamine is only slightly soluble in water . T he energy released when phenylamine form hydrogen bonds with the water molecules can overcome the attractions (hydrogen bonds and id-id itneractions) between phenylamine molecules and the hydrogen bonds between water molecules. However, energy is also needed to overcome t