Nitrogen Compounds (Org. Chem)

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### Amines: Introduction & Classification - **Definition:** Organic compounds derived from ammonia (NH₃) by replacing one or more hydrogen atoms with alkyl or aryl groups. - **Classification:** - **Primary (1°):** One alkyl/aryl group attached to nitrogen ($R-NH_2$). E.g., Methylamine ($CH_3NH_2$). - **Secondary (2°):** Two alkyl/aryl groups attached to nitrogen ($R_2NH$). E.g., Dimethylamine ($(CH_3)_2NH$). - **Tertiary (3°):** Three alkyl/aryl groups attached to nitrogen ($R_3N$). E.g., Trimethylamine ($(CH_3)_3N$). - **Quaternary Ammonium Salts:** Nitrogen atom bonded to four alkyl/aryl groups, carrying a positive charge ($R_4N^+X^-$). - **Structure:** Nitrogen is $sp^3$ hybridized, pyramidal shape due to lone pair of electrons. ### Amines: Nomenclature - **Common Names:** Alkylamines (e.g., Ethylamine). For 2°/3°, list alkyl groups alphabetically (e.g., Ethylmethylamine). - **IUPAC Names:** Alkanamines. Drop 'e' from alkane and add 'amine'. - $CH_3CH_2NH_2$: Ethanamine - $CH_3NHCH_3$: N-Methylmethanamine - $(CH_3)_3N$: N,N-Dimethylmethanamine - **Aromatic Amines:** Aniline (Benzenamine) is the simplest. Substituents are numbered relative to the amino group. ### Amines: Preparation Methods #### 1. Reduction of Nitro Compounds - **Reaction:** $\text{R-NO}_2 \xrightarrow[\text{or } Fe/HCl, Sn/HCl]{\text{H}_2/Pd, Pt, Ni} \text{R-NH}_2$ - **Aromatic:** Nitrobenzene $\xrightarrow{\text{Sn/HCl or Fe/HCl}} $ Aniline. #### 2. Ammonolysis of Alkyl Halides - **Reaction:** $\text{R-X} + \text{NH}_3 \rightarrow \text{R-NH}_2 + \text{HX}$ - **Issue:** Leads to a mixture of 1°, 2°, 3° amines and quaternary ammonium salts. - **Control:** Excess $NH_3$ favors 1° amine. #### 3. Reduction of Nitriles - **Reaction:** $\text{R-C}\equiv\text{N} \xrightarrow[\text{or } Na(Hg)/C_2H_5OH]{\text{LiAlH}_4/\text{Ether}} \text{R-CH}_2\text{NH}_2$ - **Product:** Primary amine with one more carbon atom than the original nitrile. #### 4. Reduction of Amides - **Reaction:** $\text{R-CONH}_2 \xrightarrow{\text{LiAlH}_4/\text{Ether}} \text{R-CH}_2\text{NH}_2$ - **Product:** Primary amine with the same number of carbon atoms as the original amide. #### 5. Gabriel Phthalimide Synthesis - **Purpose:** Preparation of pure primary amines (1° amines). - **Mechanism:** 1. Phthalimide reacts with ethanolic KOH to form potassium phthalimide. 2. Potassium phthalimide reacts with alkyl halide (R-X) to form N-alkylphthalimide. 3. N-alkylphthalimide is hydrolyzed with dilute HCl or NaOH to yield 1° amine and phthalic acid/salt. - **Limitation:** Cannot prepare aromatic 1° amines (aryl halides do not undergo nucleophilic substitution with potassium phthalimide). #### 6. Hoffmann Bromamide Degradation Reaction - **Reaction:** $\text{R-CONH}_2 + \text{Br}_2 + 4\text{NaOH} \rightarrow \text{R-NH}_2 + \text{Na}_2\text{CO}_3 + 2\text{NaBr} + 2\text{H}_2\text{O}$ - **Product:** Primary amine with one carbon atom less than the original amide. - **Key Feature:** Carbonyl group is lost. ### Amines: Physical Properties - **State:** Lower aliphatic amines are gases (fishy odor), C₃ to C₁₁ are liquids, higher ones are solids. Aniline is a colorless liquid. - **Boiling Points:** - Order: 1° > 2° > 3° (for comparable molar masses). - Due to hydrogen bonding: 1° amines have two H atoms for H-bonding, 2° amines have one, 3° amines have none. - Amines have lower boiling points than alcohols of comparable molar mass (N is less electronegative than O). - **Solubility:** - Lower aliphatic amines are soluble in water due to H-bonding. - Solubility decreases with increasing molar mass (hydrophobic alkyl part increases). - Aromatic amines (e.g., Aniline) are largely insoluble in water. ### Amines: Chemical Properties #### 1. Basic Character of Amines - **Reason:** Presence of a lone pair of electrons on the nitrogen atom, making them Lewis bases. - **Factors affecting basicity:** - **Alkyl amines (gas phase):** $3^\circ > 2^\circ > 1^\circ > NH_3$. Alkyl groups are electron-donating (+I effect), increasing electron density on N. - **Alkyl amines (aqueous solution):** - **Methyl substituted:** $2^\circ > 1^\circ > 3^\circ > NH_3$ - **Ethyl substituted:** $2^\circ > 3^\circ > 1^\circ > NH_3$ - **Reason:** Combination of +I effect, steric hindrance, and solvation effects. Solvation stabilizes the conjugate acid. - **Aromatic amines vs. Aliphatic amines:** Aliphatic amines are stronger bases than aromatic amines. - **Reason:** In aromatic amines (e.g., Aniline), the lone pair on N is delocalized into the benzene ring via resonance, making it less available for protonation. - **Effect of substituents on Aniline:** - **Electron-donating groups** (-CH₃, -OCH₃) increase basicity. - **Electron-withdrawing groups** (-NO₂, -COOH, -SO₃H, -X) decrease basicity. (e.g., p-nitroaniline is less basic than aniline). #### 2. Alkylation (Hofmann Elimination) - Amines react with alkyl halides to form higher substituted amines. $R-NH_2 \xrightarrow{R'X} R-NHR' \xrightarrow{R'X} R-NR'_2 \xrightarrow{R'X} R-N^+R'_3 X^-$ #### 3. Acylation - Amines react with acid chlorides, anhydrides, or esters to form amides. - **Reaction:** $R-NH_2 + R'-COCl \xrightarrow{\text{Pyridine}} R-NHCOR' + HCl$ - **Note:** Pyridine is used to remove HCl formed, shifting equilibrium to the right. #### 4. Carbylamine Reaction (Isocyanide Test) - **Purpose:** Test for primary amines (aliphatic and aromatic). - **Reaction:** $\text{R-NH}_2 + \text{CHCl}_3 + 3\text{KOH(alc.)} \xrightarrow{\text{heat}} \text{R-NC} + 3\text{KCl} + 3\text{H}_2\text{O}$ - **Product:** Isocyanide (carbylamine) with a highly offensive smell. - **Note:** Secondary and tertiary amines do not give this reaction. #### 5. Reaction with Nitrous Acid ($HNO_2$) - **Preparation:** $HNO_2$ is prepared in situ from $NaNO_2 + HCl$. - **Primary Aliphatic Amines:** React to form highly unstable diazonium salts, which immediately decompose to form alcohols with evolution of $N_2$ gas. - $\text{R-NH}_2 + HNO_2 \xrightarrow{0-5^\circ C} [\text{R-N}_2^+\text{Cl}^-] \xrightarrow{H_2O} \text{R-OH} + N_2 \uparrow + HCl$ - **Primary Aromatic Amines (Diazotisation):** React to form stable arenediazonium salts at low temperatures ($0-5^\circ C$). - $\text{Ar-NH}_2 + HNO_2 + HCl \xrightarrow{0-5^\circ C} [\text{Ar-N}_2^+\text{Cl}^-] + 2\text{H}_2\text{O}$ - **Secondary Amines:** Form N-nitrosoamines (yellow oily compounds). $R_2NH + HNO_2 \rightarrow R_2N-NO + H_2O$ - **Tertiary Amines:** Aliphatic tertiary amines form trialkylammonium nitrite salts. Aromatic tertiary amines undergo electrophilic substitution at para position. #### 6. Reaction with Arylsulphonyl Chloride (Hinsberg's Reagent) - **Reagent:** Benzenesulphonyl chloride ($C_6H_5SO_2Cl$). - **Purpose:** Distinguish between 1°, 2°, and 3° amines. - **Primary Amine:** Forms N-alkylbenzenesulphonamide, which is acidic due to the H attached to N and soluble in NaOH. - $\text{R-NH}_2 + C_6H_5SO_2Cl \rightarrow C_6H_5SO_2NHR + HCl$ - $C_6H_5SO_2NHR + NaOH \rightarrow C_6H_5SO_2N^-R Na^+ + H_2O$ (soluble) - **Secondary Amine:** Forms N,N-dialkylbenzenesulphonamide, which is not acidic (no H on N) and insoluble in NaOH. - $R_2NH + C_6H_5SO_2Cl \rightarrow C_6H_5SO_2NR_2 + HCl$ (insoluble in NaOH) - **Tertiary Amine:** Does not react with Hinsberg's reagent. It dissolves in HCl (from reagent hydrolysis) but remains insoluble in NaOH. #### 7. Electrophilic Substitution (Aromatic Amines) - **Amino group (-NH₂):** Strong activating group and o,p-directing. - **Bromination:** Aniline reacts with Bromine water to give 2,4,6-tribromoaniline (white precipitate). - To get monobromoaniline, first protect the -NH₂ group by acetylation (forming acetanilide), then brominate, then hydrolyze. - **Nitration:** Direct nitration of aniline is difficult due to oxidation and formation of m-nitroaniline (anilinium ion is meta-directing). - Protect -NH₂ group by acetylation, then nitrate, then hydrolyze. - **Sulphonation:** Aniline reacts with conc. H₂SO₄ to form Anilinium hydrogen sulphate, which on heating gives sulphanilic acid (a zwitterion). ### Diazonium Salts #### 1. Preparation (Diazotisation) - $\text{Ar-NH}_2 + NaNO_2 + 2HCl \xrightarrow{0-5^\circ C} \text{Ar-N}_2^+\text{Cl}^- + NaCl + 2H_2O$ - Aromatic diazonium salts are stable at $0-5^\circ C$ due to resonance stabilization of the diazonium group with the benzene ring. - Aliphatic diazonium salts are highly unstable and decompose immediately. #### 2. Chemical Reactions - **Reactions involving replacement of Nitrogen:** - **Sandmeyer Reaction:** - $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{CuCl/HCl} \text{Ar-Cl}$ - $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{CuBr/HBr} \text{Ar-Br}$ - $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{CuCN/KCN} \text{Ar-CN}$ - **Gattermann Reaction:** Similar to Sandmeyer, but uses copper powder/HX. Less yield. - $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{Cu/HCl} \text{Ar-Cl}$ - $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{Cu/HBr} \text{Ar-Br}$ - **Replacement by Iodine:** $\text{Ar-N}_2^+\text{Cl}^- + KI \rightarrow \text{Ar-I} + N_2 + KCl$ - **Replacement by Fluorine (Balz-Schiemann Reaction):** - $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{HBF_4} \text{Ar-N}_2^+\text{BF}_4^- \xrightarrow{\text{heat}} \text{Ar-F} + BF_3 + N_2$ - **Replacement by H (Reduction):** $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{H_3PO_2/\text{H}_2O \text{ or } C_2H_5OH} \text{Ar-H} + N_2 + H_3PO_3/CH_3CHO + HCl$ - **Replacement by -OH:** $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{H_2O/\text{warm}} \text{Ar-OH} + N_2 + HCl$ - **Replacement by -NO₂:** $\text{Ar-N}_2^+\text{Cl}^- \xrightarrow{NaNO_2/Cu} \text{Ar-NO}_2 + N_2 + CuCl$ - **Reactions involving retention of Nitrogen (Coupling Reactions):** - Diazonium salts act as electrophiles and react with electron-rich aromatic compounds (phenols, anilines) to form azo compounds (colored dyes). - **With Phenol:** $\text{Ar-N}_2^+\text{Cl}^- + C_6H_5OH \xrightarrow{H^+/\text{weakly acidic/alkaline}} \text{Ar-N}=\text{N}-C_6H_4-OH \text{ (p-hydroxyazobenzene, orange dye)}$ - **With Aniline:** $\text{Ar-N}_2^+\text{Cl}^- + C_6H_5NH_2 \xrightarrow{H^+/\text{weakly acidic}} \text{Ar-N}=\text{N}-C_6H_4-NH_2 \text{ (p-aminoazobenzene, yellow dye)}$ ### Nitro Compounds - **Definition:** Organic compounds containing the nitro group (-NO₂). - **Aliphatic Nitro Compounds:** $R-NO_2$. - **Aromatic Nitro Compounds:** $Ar-NO_2$. - **Nomenclature:** Nitroalkanes (e.g., Nitromethane $CH_3NO_2$). Nitrobenzene $C_6H_5NO_2$. - **Preparation:** - **Aliphatic:** Reaction of alkyl halides with $NaNO_2$. $R-X + NaNO_2 \rightarrow R-NO_2 + NaX$ - **Aromatic:** Nitration of benzene (or substituted benzene) with conc. $HNO_3$ and conc. $H_2SO_4$. - **Chemical Reactions:** - **Reduction:** Primary aliphatic nitro compounds can be reduced to 1° amines. - $R-NO_2 \xrightarrow{H_2/Pd} R-NH_2$ - $C_6H_5NO_2 \xrightarrow{Sn/HCl \text{ or } Fe/HCl} C_6H_5NH_2$ (Aniline) - **Electrophilic Substitution (Aromatic):** -NO₂ group is a strong deactivating and meta-directing group. ### Cyanides and Isocyanides #### 1. Cyanides (Nitriles) - **Formula:** $R-C\equiv N$ - **Nomenclature:** Alkanenitriles (e.g., Ethanenitrile, $CH_3CN$). - **Preparation:** - From alkyl halides: $R-X + KCN \xrightarrow{Ethanol/H_2O} R-CN + KX$ - From amides (dehydration): $R-CONH_2 \xrightarrow{P_2O_5/\text{heat}} R-CN + H_2O$ - **Chemical Reactions:** - **Hydrolysis:** - Partial hydrolysis: $R-CN + H_2O \xrightarrow{H^+/\text{dil. alkali}} R-CONH_2$ (Amide) - Complete hydrolysis: $R-CN + 2H_2O \xrightarrow{H^+/\text{alkali}} R-COOH + NH_3$ (Carboxylic acid) - **Reduction:** - $R-CN \xrightarrow{LiAlH_4/\text{Ether} \text{ or } H_2/Ni} R-CH_2NH_2$ (Primary amine) - Stephen reaction: $R-CN \xrightarrow{SnCl_2/HCl \text{ then } H_3O^+} R-CHO$ (Aldehyde) #### 2. Isocyanides (Carbylamines) - **Formula:** $R-N^+\equiv C^-$ (or $R-N=C$) - **Nomenclature:** Alkyl isocyanides (e.g., Methyl isocyanide, $CH_3NC$). - **Preparation:** Carbylamine reaction (from 1° amines). - **Chemical Reactions:** - **Hydrolysis:** $R-NC + 2H_2O \xrightarrow{H^+/\text{heat}} R-NH_2 + HCOOH$ (Primary amine + Formic acid) - **Reduction:** $R-NC \xrightarrow{H_2/Ni \text{ or } LiAlH_4} R-NHCH_3$ (Secondary amine)