Organic Chemistry JEE Mains

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General Organic Chemistry (GOC) Electronic Effects Inductive Effect (I-Effect): Permanent displacement of $\sigma$-electrons towards more electronegative atom. $+I$ groups: alkyl groups (e.g., $-\mathrm{CH}_3$, $-\mathrm{C}_2\mathrm{H}_5$) $-I$ groups: $-\mathrm{NO}_2$, $-\mathrm{CN}$, $-\mathrm{COOH}$, $-\mathrm{F}$, $-\mathrm{Cl}$, $-\mathrm{Br}$, $-\mathrm{I}$ Stability of carbocations: $3^\circ > 2^\circ > 1^\circ > \mathrm{CH}_3^+$ Stability of carbanions: $\mathrm{CH}_3^- > 1^\circ > 2^\circ > 3^\circ$ Resonance Effect (M-Effect): Delocalization of $\pi$-electrons. $+M$ groups: $-\mathrm{OH}$, $-\mathrm{OR}$, $-\mathrm{NH}_2$, $-\mathrm{NR}_2$, $-\mathrm{X}$ (halogens) - donate electrons $-M$ groups: $-\mathrm{CHO}$, $-\mathrm{COR}$, $-\mathrm{COOH}$, $-\mathrm{COOR}$, $-\mathrm{CN}$, $-\mathrm{NO}_2$ - withdraw electrons Hyperconjugation: Delocalization of $\sigma$-electrons of C-H bond with adjacent empty p-orbital (carbocation) or $\pi$-orbital (alkene/alkyl benzene). "No bond resonance". More $\alpha$-hydrogens $\implies$ more hyperconjugation $\implies$ more stability. Stability of alkenes: more substituted $\implies$ more stable. Acidity and Basicity Acidity: Directly proportional to stability of conjugate base. Factors increasing acidity: $-I$, $-M$ groups; higher s-character (e.g., $\mathrm{sp} > \mathrm{sp}^2 > \mathrm{sp}^3$) Carboxylic acids $>$ Phenols $>$ Alcohols $>$ Alkynes Order for substituted carboxylic acids: $\mathrm{FCH}_2\mathrm{COOH} > \mathrm{ClCH}_2\mathrm{COOH} > \mathrm{BrCH}_2\mathrm{COOH} > \mathrm{CH}_3\mathrm{COOH}$ Basicity: Directly proportional to electron density on the atom and availability of lone pair. Factors increasing basicity: $+I$, $+M$ groups. Amines: Gas phase: $3^\circ > 2^\circ > 1^\circ > \mathrm{NH}_3$ Aqueous phase (steric + solvation): $2^\circ > 1^\circ > 3^\circ > \mathrm{NH}_3$ (for $\mathrm{CH}_3$) or $2^\circ > 3^\circ > 1^\circ > \mathrm{NH}_3$ (for $\mathrm{C}_2\mathrm{H}_5$) Aromatic amines are less basic than aliphatic amines due to resonance. Isomerism Compounds having the same molecular formula but different physical or chemical properties. 1. Structural Isomerism (Constitutional Isomerism) Same molecular formula, different connectivity of atoms. Chain Isomerism: Different carbon skeletons. Example: $n$-butane ($\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CH}_3$) and isobutane ($\mathrm{CH}(\mathrm{CH}_3)_3$). Position Isomerism: Same carbon skeleton, different position of functional group/substituent/multiple bond. Example: Butan-1-ol ($\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{CH}_2\mathrm{OH}$) and Butan-2-ol ($\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}(\mathrm{OH})\mathrm{CH}_3$). Functional Group Isomerism: Different functional groups. Example: Ethanol ($\mathrm{CH}_3\mathrm{CH}_2\mathrm{OH}$) and Dimethyl ether ($\mathrm{CH}_3\mathrm{OCH}_3$). Aldehydes and Ketones (e.g., Propanal and Propanone). Carboxylic Acids and Esters (e.g., Propanoic acid and Methyl acetate). Metamerism: Different alkyl groups attached to the same polyvalent functional group. Example: Diethyl ether ($\mathrm{CH}_3\mathrm{CH}_2\mathrm{OCH}_2\mathrm{CH}_3$) and Methyl propyl ether ($\mathrm{CH}_3\mathrm{OCH}_2\mathrm{CH}_2\mathrm{CH}_3$). Tautomerism: Special type of functional isomerism where isomers exist in dynamic equilibrium, usually involving migration of a proton and a double bond. Keto-enol Tautomerism: Most common. Requires an $\alpha$-hydrogen. R-CO-CH2-R' R-C(OH)=CH-R' (Keto form) (Enol form) Example: Acetone ($\mathrm{CH}_3\mathrm{COCH}_3$) and Propen-2-ol ($\mathrm{CH}_2=\mathrm{C}(\mathrm{OH})\mathrm{CH}_3$). 2. Stereoisomerism Same molecular formula, same connectivity, different spatial arrangement of atoms. Conformational Isomerism: Different spatial arrangements arising from rotation about single bonds. Interconvertible at room temperature. Example: Ethane (staggered, eclipsed), Cyclohexane (chair, boat). Configurational Isomerism: Interconversion requires bond breaking. Geometrical Isomerism (cis-trans or E/Z): Restricted rotation around a double bond or in a cyclic structure. Requires each carbon of the double bond to be attached to two different groups. Cis/Trans: For simple cases. Cis if identical groups are on the same side, trans if on opposite sides. E/Z (Entgegen/Zusammen): For more complex cases. E (opposite) if higher priority groups are on opposite sides, Z (same) if on the same side (Cahn-Ingold-Prelog rules for priority). Example: But-2-ene. Cis-but-2-ene has two methyl groups on the same side of the double bond. Trans-but-2-ene has two methyl groups on opposite sides. Optical Isomerism: Due to chirality (non-superimposable mirror images). Chiral Center: An atom (usually carbon) bonded to four different groups. Enantiomers: Stereoisomers that are non-superimposable mirror images of each other. They have identical physical and chemical properties (except rotation of plane-polarized light and reaction with other chiral molecules). Rotate plane-polarized light in equal but opposite directions (dextrorotatory 'd' or '+', levorotatory 'l' or '-'). R/S Configuration: Absolute configuration based on Cahn-Ingold-Prelog priority rules. Diastereomers: Stereoisomers that are not mirror images of each other. They have different physical and chemical properties. Meso Compounds: Compounds that possess chiral centers but are optically inactive due to the presence of an internal plane of symmetry. Racemic Mixture: An equimolar mixture of a pair of enantiomers. Optically inactive due to external compensation. Resolution is the process of separating enantiomers. Nomenclature (IUPAC) Systematic naming of organic compounds. Identify the longest continuous carbon chain: This is the parent chain. If a functional group is present, the chain containing the functional group is chosen, even if it's not the longest. Number the parent chain: Start numbering from the end that gives the lowest locant (number) to the principal functional group. If multiple bonds are present, they get preference over substituents. If both double and triple bonds are present, number from the end that gives the lowest locant to the first multiple bond. If a choice remains, give the lowest locant to the double bond. Identify and name substituents: Alkyl groups: methyl, ethyl, propyl, isopropyl, etc. Halogens: fluoro, chloro, bromo, iodo. Other groups: nitro ($\mathrm{NO}_2$), methoxy ($\mathrm{OCH}_3$), etc. Alphabetize substituents: Before the parent chain name, list substituents in alphabetical order. Prefixes like di-, tri-, tetra-, sec-, tert- are ignored for alphabetization (but iso-, neo- are included). Combine into a single name: Locant for functional group (suffix) or substituent (prefix). Parent chain name. Suffix for functional group. Priority of Functional Groups (decreasing order): Carboxylic Acid ($\mathrm{COOH}$) > Sulfonic Acid ($\mathrm{SO}_3\mathrm{H}$) > Ester ($\mathrm{COOR}$) > Acid Halide ($\mathrm{COX}$) > Amide ($\mathrm{CONH}_2$) > Nitrile ($\mathrm{CN}$) > Aldehyde ($\mathrm{CHO}$) > Ketone ($\mathrm{CO}$) > Alcohol ($\mathrm{OH}$) > Amine ($\mathrm{NH}_2$) > Alkene (ene) > Alkyne (yne) > Alkane (ane) > Ether ($\mathrm{OR}$) > Halogen ($\mathrm{X}$) > Nitro ($\mathrm{NO}_2$). Example 1: $\mathrm{CH}_3-\mathrm{CH}_2-\mathrm{CH}(\mathrm{OH})-\mathrm{CH}_3$ Parent chain: Butane. Functional group: $-\mathrm{OH}$ (alcohol). Numbering from right gives $-\mathrm{OH}$ at C-2. Name: Butan-2-ol. Example 2: $\mathrm{CH}_3-\mathrm{CH}(\mathrm{Cl})-\mathrm{CH}_2-\mathrm{COOH}$ Parent chain: Butanoic acid. Functional group: $-\mathrm{COOH}$ (priority 1). Numbering from $-\mathrm{COOH}$ end. Substituent: Chloro at C-3. Name: 3-Chlorobutanoic acid. Example 3: $\mathrm{CH}_2=\mathrm{CH}-\mathrm{CH}_2-\mathrm{CHO}$ Parent chain: Butanal. Functional group: $-\mathrm{CHO}$ (aldehyde) at C-1. Double bond at C-2. Name: But-2-enal. Hydrocarbons Alkanes Preparation: Hydrogenation of alkenes/alkynes (Raney $\mathrm{Ni}$, $\mathrm{Pt}$, $\mathrm{Pd}$): $\mathrm{R-CH=CH-R'} + \mathrm{H}_2 \xrightarrow{\mathrm{Ni}/\mathrm{Pt}/\mathrm{Pd}} \mathrm{R-CH}_2\mathrm{CH}_2\mathrm{R'}$. Wurtz Reaction: $2\mathrm{RX} + 2\mathrm{Na} \xrightarrow{\text{dry ether}} \mathrm{R-R} + 2\mathrm{NaX}$ (for symmetrical alkanes, odd number carbons are difficult). Example: $2\mathrm{CH}_3\mathrm{Cl} + 2\mathrm{Na} \xrightarrow{\text{dry ether}} \mathrm{CH}_3\mathrm{CH}_3 + 2\mathrm{NaCl}$. Decarboxylation: $\mathrm{RCOONa} + \mathrm{NaOH} \xrightarrow{\mathrm{CaO}, \Delta} \mathrm{RH} + \mathrm{Na}_2\mathrm{CO}_3$. Example: $\mathrm{CH}_3\mathrm{COONa} + \mathrm{NaOH} \xrightarrow{\mathrm{CaO}, \Delta} \mathrm{CH}_4 + \mathrm{Na}_2\mathrm{CO}_3$. Reactions: Free Radical Halogenation ($\mathrm{Cl}_2/\mathrm{Br}_2$, $\mathrm{h}\nu$ or $\Delta$): $\mathrm{CH}_4 + \mathrm{Cl}_2 \xrightarrow{\mathrm{h}\nu} \mathrm{CH}_3\mathrm{Cl} + \mathrm{HCl}$. Selectivity: $3^\circ > 2^\circ > 1^\circ$. Combustion: $\mathrm{CH}_4 + 2\mathrm{O}_2 \to \mathrm{CO}_2 + 2\mathrm{H}_2\mathrm{O}$. Alkenes Preparation: Dehydration of alcohols ($\mathrm{H}_2\mathrm{SO}_4$, $\Delta$): Saytzeff's rule (most substituted alkene). Example: $\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}(\mathrm{OH})\mathrm{CH}_3 \xrightarrow{\text{conc. } \mathrm{H}_2\mathrm{SO}_4, \Delta} \mathrm{CH}_3\mathrm{CH}=\mathrm{CHCH}_3$ (major) + $\mathrm{CH}_2=\mathrm{CHCH}_2\mathrm{CH}_3$ (minor). Dehydrohalogenation of alkyl halides (alcoholic $\mathrm{KOH}$): Saytzeff's rule. Example: $\mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}(\mathrm{Br})\mathrm{CH}_3 + \text{alc. KOH} \to \mathrm{CH}_3\mathrm{CH}=\mathrm{CHCH}_3$ (major) + $\mathrm{CH}_2=\mathrm{CHCH}_2\mathrm{CH}_3$ (minor) + $\mathrm{KBr} + \mathrm{H}_2\mathrm{O}$. Dehalogenation of vicinal dihalides ($\mathrm{Zn}$ dust). Partial hydrogenation of alkynes (Lindlar's catalyst for cis-alkene, $\mathrm{Na}/\mathrm{NH}_3(l)$ for trans-alkene). Example: $\mathrm{R-C}\equiv\mathrm{C-R'} + \mathrm{H}_2 \xrightarrow{\text{Pd/BaSO}_4, \text{CaCO}_3, \text{quinoline}} \text{cis-R-CH=CH-R'}$ (Lindlar's). $\mathrm{R-C}\equiv\mathrm{C-R'} + \mathrm{Na}/\mathrm{NH}_3(l) \to \text{trans-R-CH=CH-R'}$ (Birch reduction). Reactions: Electrophilic Addition: $\mathrm{HBr}/\mathrm{HCl}/\mathrm{HI}$: Markovnikov's rule (H to C with more H's). Example: $\mathrm{CH}_3\mathrm{CH}=\mathrm{CH}_2 + \mathrm{HBr} \to \mathrm{CH}_3\mathrm{CH}(\mathrm{Br})\mathrm{CH}_3$. Anti-Markovnikov with $\mathrm{HBr}$ in presence of peroxide (Kharasch effect). Example: $\mathrm{CH}_3\mathrm{CH}=\mathrm{CH}_2 + \mathrm{HBr} \xrightarrow{\text{Peroxide}} \mathrm{CH}_3\mathrm{CH}_2\mathrm{CH}_2\mathrm{Br}$. $\mathrm{H}_2\mathrm{O}/\mathrm{H}^+$ (hydration): Markovnikov. $\mathrm{Br}_2/\mathrm{Cl}_2$: Anti-addition (vicinal dihalide). $\mathrm{HBr}/\mathrm{NBS}$: Allylic bromination. Oxidation: Baeyer's Reagent (cold, dilute, alkaline $\mathrm{KMnO}_4$): forms vicinal diols (syn-addition). Example: $\mathrm{R-CH=CH-R'} \xrightarrow{\text{cold dil. KMnO}_4} \mathrm{R-CH(OH)-CH(OH)-R'}$. Hot, acidic $\mathrm{KMnO}_4$: Cleavage of double bond, forms carboxylic acids/ketones/$\mathrm{CO}_2$. Ozonolysis ($\mathrm{O}_3, \mathrm{Zn}/\mathrm{H}_2\mathrm{O}$): Cleavage of double bond, forms aldehydes/ketones. Example: $\mathrm{R-CH=CH-R'} \xrightarrow{\text{1. O}_3, \text{2. Zn/H}_2\mathrm{O}} \mathrm{R-CHO} + \mathrm{R'-CHO}$. Polymerization. Alkynes Preparation: From vicinal/geminal dihalides (alcoholic $\mathrm{KOH}$ then $\mathrm{NaNH}_2$). From Calcium Carbide: $\mathrm{CaC}_2 + 2\mathrm{H}_2\mathrm{O} \to \mathrm{HC}\equiv\mathrm{CH} + \mathrm{Ca}(\mathrm{OH})_2$. Reactions: Acidic nature of terminal alkynes: $\mathrm{RC}\equiv\mathrm{CH} + \mathrm{NaNH}_2 \to \mathrm{RC}\equiv\mathrm{C}^-\mathrm{Na}^+ + \mathrm{NH}_3$. Forms silver/copper acetylides. Electrophilic Addition: Similar to alkenes, but two additions. Markovnikov's rule. Hydration ($\mathrm{H}_2\mathrm{O}, \mathrm{HgSO}_4/\mathrm{H}_2\mathrm{SO}_4$): Forms ketones (except ethyne $\to$ ethanal). Example: $\mathrm{CH}\equiv\mathrm{CH} + \mathrm{H}_2\mathrm{O} \xrightarrow{\mathrm{HgSO}_4/\mathrm{H}_2\mathrm{SO}_4} [\mathrm{CH}_2=\mathrm{CH-OH}] \xrightarrow{\text{tautomerism}} \mathrm{CH}_3\mathrm{CHO}$. Polymerization: Linear (e.g., ethyne to polyacetylene) or cyclic (e.g., ethyne to benzene at red hot iron tube). Aromatic Compounds (Benzene) Electrophilic Aromatic Substitution (EAS): Nitration: Benzene + $\mathrm{HNO}_3/\mathrm{H}_2\mathrm{SO}_4 \to$ Nitrobenzene + $\mathrm{H}_2\mathrm{O}$. ($\mathrm{NO}_2^+$ is the electrophile). Halogenation: Benzene + $\mathrm{X}_2 + \mathrm{FeX}_3$. Sulfonation: Benzene + Conc. $\mathrm{H}_2\mathrm{SO}_4$. Reversible. Friedel-Crafts Alkylation: Benzene + $\mathrm{RCl} + \mathrm{AlCl}_3 \to$ Alkylbenzene + $\mathrm{HCl}$. Polyalkylation, rearrangement. Friedel-Crafts Acylation: Benzene + $\mathrm{RCOCl} + \mathrm{AlCl}_3 \to$ Acylbenzene + $\mathrm{HCl}$. No polyacylation, no rearrangement. Directing Groups: Ortho-para directing, activating: $-\mathrm{OH}$, $-\mathrm{OR}$, $-\mathrm{NH}_2$, $-\mathrm{NR}_2$, $-\mathrm{CH}_3$, $-\mathrm{R}$ (alkyl groups). Ortho-para directing, deactivating: Halogens ($\mathrm{F}, \mathrm{Cl}, \mathrm{Br}, \mathrm{I}$). Meta directing, deactivating: $-\mathrm{NO}_2$, $-\mathrm{CN}$, $-\mathrm{CHO}$, $-\mathrm{COR}$, $-\mathrm{COOH}$, $-\mathrm{COOR}$, $-\mathrm{SO}_3\mathrm{H}$. Alkyl Halides and Aryl Halides Alkyl Halides (R-X) Preparation: From alcohols: $\mathrm{ROH} + \mathrm{HX} \xrightarrow{\mathrm{ZnCl}_2} \mathrm{RX}$ (Lucas test for $1^\circ, 2^\circ, 3^\circ$ alcohols). $\mathrm{ROH} + \mathrm{PCl}_5 \to \mathrm{RCl}$. $\mathrm{ROH} + \mathrm{SOCl}_2 \to \mathrm{RCl} + \mathrm{SO}_2 + \mathrm{HCl}$ (Darzen's reaction, best method). From hydrocarbons: Free radical halogenation (alkanes), Electrophilic addition (alkenes). Halogen exchange: Finkelstein reaction ($\mathrm{RI}$ from $\mathrm{RCl}/\mathrm{RBr}$ using $\mathrm{NaI}$ in acetone). Swarts reaction ($\mathrm{RF}$ from $\mathrm{RCl}/\mathrm{RBr}$ using $\mathrm{AgF}/\mathrm{Hg}_2\mathrm{F}_2/\mathrm{CoF}_2/\mathrm{SbF}_3$). Reactions: Nucleophilic Substitution ($\mathrm{S_N}1, \mathrm{S_N}2$): $\mathrm{S_N}1$: $3^\circ > 2^\circ > 1^\circ$. Two steps, carbocation intermediate, racemization. Step 1: R3C-X --> R3C+ + X- (slow, rate-determining) Step 2: R3C+ + Nu- --> R3C-Nu $\mathrm{S_N}2$: $1^\circ > 2^\circ > 3^\circ$. One step, concerted, inversion of configuration (Walden inversion). Nu- + R-CH2-X --> [Nu---CH2---X]- (transition state) --> Nu-CH2-R + X- Reactivity order of leaving groups: $\mathrm{I}^- > \mathrm{Br}^- > \mathrm{Cl}^- > \mathrm{F}^-$. Elimination (E1, E2): E1: $3^\circ > 2^\circ > 1^\circ$. Two steps, carbocation intermediate. E2: $3^\circ > 2^\circ > 1^\circ$. One step, concerted, anti-periplanar transition state. Strong base/high temperature favors elimination. Reaction with metals: Grignard reagent ($\mathrm{RMgX}$), Wurtz reaction. Aryl Halides (Ar-X) Less reactive towards nucleophilic substitution due to resonance stabilization of C-X bond and $\mathrm{sp}^2$ hybridized carbon. Reactivity increased by electron-withdrawing groups at ortho/para position (e.g., $-\mathrm{NO}_2$). Nucleophilic Substitution: Requires harsh conditions (high T, P) or strong electron-withdrawing groups (e.g., Dow's process for chlorobenzene to phenol). Electrophilic Substitution: Halogens are deactivating but o,p-directing. Alcohols, Phenols, Ethers Alcohols (R-OH) Preparation: From alkenes: Acid-catalyzed hydration (Markovnikov), Hydroboration-oxidation ($\mathrm{BH}_3/\mathrm{H}_2\mathrm{O}_2, \mathrm{OH}^-$, Anti-Markovnikov). From aldehydes/ketones: Reduction with $\mathrm{LiAlH}_4$ or $\mathrm{NaBH}_4$. From Grignard reagents: $\mathrm{RMgX} + \mathrm{HCHO} \to 1^\circ$. $\mathrm{RMgX} + \mathrm{R'CHO} \to 2^\circ$. $\mathrm{RMgX} + \mathrm{R'COR''} \to 3^\circ$. Reactions: Acidity: $\mathrm{H}_2\mathrm{O} > \mathrm{ROH}$. $1^\circ > 2^\circ > 3^\circ$ (due to $+I$ effect). Reaction with $\mathrm{Na}$: $2\mathrm{ROH} + 2\mathrm{Na} \to 2\mathrm{RONa} + \mathrm{H}_2$. Esterification: $\mathrm{ROH} + \mathrm{R'COOH} \rightleftharpoons \mathrm{R'COOR} + \mathrm{H}_2\mathrm{O}$. Oxidation: $1^\circ \mathrm{ROH} \xrightarrow{\mathrm{PCC}} \mathrm{RCHO}$. $\xrightarrow{\text{strong oxidizing agent}} \mathrm{RCOOH}$. $2^\circ \mathrm{ROH} \xrightarrow{\text{oxidizing agent}} \mathrm{RCOR'}$. $3^\circ \mathrm{ROH}$: Resistant to oxidation under mild conditions, undergo dehydration under strong conditions. Dehydration: $\mathrm{ROH} \xrightarrow{\text{conc. } \mathrm{H}_2\mathrm{SO}_4, 413\mathrm{K}} \text{Alkene}$ (Saytzeff). Reaction with $\mathrm{HX}$, $\mathrm{PX}_3$, $\mathrm{SOCl}_2$ (formation of alkyl halides). Phenols (Ar-OH) Preparation: From Haloarenes (Dow's process): Chlorobenzene $\xrightarrow{\mathrm{NaOH}, 623\mathrm{K}, 300 \text{ atm}}$ Phenol. From Benzene sulfonic acid: $\mathrm{C_6H_5SO_3H} \xrightarrow{\mathrm{NaOH}, \Delta} \mathrm{C_6H_5ONa} \xrightarrow{\mathrm{H}^+} \text{Phenol}$. From Diazonium salts: $\mathrm{ArN_2^+Cl^-} \xrightarrow{\mathrm{H}_2\mathrm{O}, \Delta} \text{Phenol}$. From Cumene: Cumene $\xrightarrow{\mathrm{O}_2} \text{Cumene hydroperoxide} \xrightarrow{\mathrm{H}^+} \text{Phenol + Acetone}$. Reactions: Acidity: Phenol $>$ Alcohols. Electron-withdrawing groups increase acidity (ortho/para $-\mathrm{NO}_2$). Electron-donating groups decrease acidity. Electrophilic Aromatic Substitution: Highly activating, o,p-directing. Nitration: Dilute $\mathrm{HNO}_3 \to \text{o- and p-nitrophenol}$. Conc. $\mathrm{HNO}_3 \to \text{2,4,6-trinitrophenol (Picric acid)}$. Bromination: $\mathrm{Br}_2/\mathrm{CS}_2 \to \text{o- and p-bromophenol}$. $\mathrm{Br}_2/\mathrm{H}_2\mathrm{O} \to \text{2,4,6-tribromophenol}$ (white ppt). Kolbe's Reaction: Phenol $\xrightarrow{\mathrm{NaOH}} \text{Sodium phenoxide} \xrightarrow{\mathrm{CO}_2, 140^\circ\mathrm{C}, 4-7 \text{ atm}} \text{Salicylic acid}$. Reimer-Tiemann Reaction: Phenol $\xrightarrow{\mathrm{CHCl}_3/\mathrm{NaOH}} \text{Salicylaldehyde}$. Reaction with $\mathrm{Zn}$ dust: Phenol $\xrightarrow{\mathrm{Zn}, \Delta} \text{Benzene}$. Oxidation: With $\mathrm{CrO}_3$ to benzoquinone. Ferric Chloride Test: Phenols give characteristic coloration with neutral $\mathrm{FeCl}_3$. Ethers (R-O-R') Preparation: Williamson Synthesis: $\mathrm{RONa} + \mathrm{R'X} \to \mathrm{ROR'} + \mathrm{NaX}$ ($1^\circ$ alkyl halide preferred to avoid elimination). Dehydration of alcohols: $2\mathrm{ROH} \xrightarrow{\text{conc. } \mathrm{H}_2\mathrm{SO}_4, 413\mathrm{K}} \mathrm{ROR} + \mathrm{H}_2\mathrm{O}$ (for $1^\circ$ alcohols). Reactions: Cleavage with $\mathrm{HI}/\mathrm{HBr}$: $\mathrm{ROR'} + \mathrm{HX} \to \mathrm{RX} + \mathrm{R'OH}$ (at room temp). If excess $\mathrm{HX}$ or higher temp, $\mathrm{RX} + \mathrm{R'X}$. Order of reactivity: $\mathrm{HI} > \mathrm{HBr} > \mathrm{HCl}$. Cleavage occurs at the smaller alkyl group for $1^\circ/2^\circ$ ethers. For $3^\circ$ ethers, $\mathrm{S_N}1$ mechanism dominates, so $\mathrm{X}$ attaches to $3^\circ$ carbon. Peroxide formation: Ethers react with $\mathrm{O}_2$ to form dangerously explosive peroxides. Aldehydes and Ketones Preparation Oxidation of alcohols: $1^\circ \mathrm{ROH} \xrightarrow{\mathrm{PCC}} \mathrm{RCHO}$. $2^\circ \mathrm{ROH} \xrightarrow{\text{oxidizing agent}} \mathrm{RCOR'}$. Ozonolysis of alkenes: $\mathrm{RCH}=\mathrm{CHR'} \xrightarrow{\mathrm{O}_3, \mathrm{Zn}/\mathrm{H}_2\mathrm{O}} \mathrm{RCHO} + \mathrm{R'CHO}$. Hydration of alkynes: $\mathrm{RC}\equiv\mathrm{CH} \xrightarrow{\mathrm{HgSO}_4/\mathrm{H}_2\mathrm{SO}_4} \mathrm{RCOR}$ (except ethyne $\to$ ethanal). From Grignard reagents: $\mathrm{RMgX} + \mathrm{HCN} \to \mathrm{RCHO}$. $\mathrm{RMgX} + \mathrm{R'CN} \to \mathrm{RCOR'}$. Specific for Aldehydes: Rosenmund Reduction: $\mathrm{RCOCl} \xrightarrow{\mathrm{H}_2, \mathrm{Pd}/\mathrm{BaSO}_4} \mathrm{RCHO}$. Stephen Reaction: $\mathrm{RCN} \xrightarrow{\mathrm{SnCl}_2/\mathrm{HCl}} \mathrm{RCH}=\mathrm{NH}\cdot\mathrm{HCl} \xrightarrow{\mathrm{H}_2\mathrm{O}} \mathrm{RCHO}$. Etard Reaction: Toluene $\xrightarrow{\mathrm{CrO}_2\mathrm{Cl}_2} \text{Chromium complex} \xrightarrow{\mathrm{H}_3\mathrm{O}^+} \text{Benzaldehyde}$. Gatterman-Koch Reaction: Benzene $\xrightarrow{\mathrm{CO}/\mathrm{HCl}, \mathrm{AlCl}_3/\mathrm{CuCl}} \text{Benzaldehyde}$. From Esters (DIBAL-H): $\mathrm{RCOOR'} \xrightarrow{\mathrm{DIBAL-H}} \mathrm{RCHO}$. Specific for Ketones: Friedel-Crafts Acylation: Benzene $\xrightarrow{\mathrm{RCOCl}/\mathrm{AlCl}_3} \mathrm{ArCOR}$. From Nitriles: $\mathrm{RCN} + \mathrm{R'MgX} \xrightarrow{\mathrm{H}_3\mathrm{O}^+} \mathrm{RCOR'}$. Reactions Nucleophilic Addition Reactions: (Aldehydes are more reactive than ketones due to steric hindrance and electronic effect). Addition of $\mathrm{HCN}$: Cyanohydrin formation. Addition of $\mathrm{NaHSO}_3$: Bisulfite addition product. Addition of Grignard reagents: Alcohols. Addition of Alcohols: Hemiacetals $\to$ Acetals (ketals for ketones). Addition of Ammonia derivatives: ($\mathrm{NH}_2\mathrm{Z}$), forms imines, oximes, hydrazones, 2,4-DNP derivatives. Reduction: To Alcohols: $\mathrm{LiAlH}_4$, $\mathrm{NaBH}_4$. Clemmensen Reduction: $\mathrm{RCHO}/\mathrm{RCOR'} \xrightarrow{\mathrm{Zn-Hg}/\text{conc. }\mathrm{HCl}} \mathrm{RCH}_3/\mathrm{RCH}_2\mathrm{R'}$. Wolff-Kishner Reduction: $\mathrm{RCHO}/\mathrm{RCOR'} \xrightarrow{\mathrm{NH}_2\mathrm{NH}_2, \mathrm{KOH}/\text{Ethylene glycol}, \Delta} \mathrm{RCH}_3/\mathrm{RCH}_2\mathrm{R'}$. Oxidation: Aldehydes easily oxidized to carboxylic acids (e.g., Tollens' reagent, Fehling's solution, Benedict's solution, mild $\mathrm{KMnO}_4$). Ketones resistant to mild oxidation, require strong conditions (cleavage of C-C bond, Popoff's rule). Aldol Condensation: Carbonyl compounds with $\alpha$-hydrogens. Forms $\beta$-hydroxy carbonyl compound, dehydrates to $\alpha,\beta$-unsaturated carbonyl compound. Example: $2\mathrm{CH}_3\mathrm{CHO} \xrightarrow{\text{dil. NaOH}} \mathrm{CH}_3\mathrm{CH}(\mathrm{OH})\mathrm{CH}_2\mathrm{CHO} \xrightarrow{\Delta} \mathrm{CH}_3\mathrm{CH}=\mathrm{CHCHO} + \mathrm{H}_2\mathrm{O}$. Cross-Aldol: Between two different aldehydes/ketones. Cannizzaro Reaction: Aldehydes without $\alpha$-hydrogens. Disproportionation reaction. Example: $2\mathrm{HCHO} \xrightarrow{\text{conc. }\mathrm{KOH}} \mathrm{CH}_3\mathrm{OH} + \mathrm{HCOOK}$. Haloform Reaction: Methyl ketones ($\mathrm{CH}_3\mathrm{CO}$ attached to C or H) or alcohols that can be oxidized to methyl ketones. Example: $\mathrm{CH}_3\mathrm{COR} + 3\mathrm{X}_2 + 4\mathrm{NaOH} \to \mathrm{CHX}_3 + \mathrm{RCOONa} + 3\mathrm{NaX} + 3\mathrm{H}_2\mathrm{O}$. Carboxylic Acids Preparation Oxidation of $1^\circ$ alcohols/aldehydes: $\mathrm{RCH}_2\mathrm{OH}/\mathrm{RCHO} \xrightarrow{\text{strong oxidizing agent}} \mathrm{RCOOH}$. From Nitriles and Amides: $\mathrm{RCN} \xrightarrow{\mathrm{H}_3\mathrm{O}^+/\Delta} \mathrm{RCOOH}$. $\mathrm{RCONH}_2 \xrightarrow{\mathrm{H}_3\mathrm{O}^+/\Delta} \mathrm{RCOOH}$. From Grignard reagents: $\mathrm{RMgX} + \mathrm{CO}_2 \xrightarrow{\text{dry ether}} \mathrm{RCOOMgX} \xrightarrow{\mathrm{H}_3\mathrm{O}^+} \mathrm{RCOOH}$. Hydrolysis of Acyl halides/Anhydrides/Esters. From Alkylbenzenes: $\mathrm{ArCH}_3 \xrightarrow{\text{strong oxidizing agent}} \mathrm{ArCOOH}$. Reactions Acidity: Carboxylic acids $>$ Phenols $>$ Alcohols. Electron-withdrawing groups increase acidity. Electron-donating groups decrease acidity. Formic acid $>$ Acetic acid. Benzoic acid is stronger than acetic acid. Formation of derivatives: Esters: Esterification with alcohol ($\mathrm{H}^+$ catalyst). Acyl chlorides: $\mathrm{RCOOH} \xrightarrow{\mathrm{PCl}_5/\mathrm{PCl}_3/\mathrm{SOCl}_2} \mathrm{RCOCl}$. Amides: $\mathrm{RCOOH} \xrightarrow{\mathrm{NH}_3, \Delta} \mathrm{RCONH}_2$. Anhydrides: $2\mathrm{RCOOH} \xrightarrow{\mathrm{P}_2\mathrm{O}_5, \Delta} (\mathrm{RCO})_2\mathrm{O}$. Reduction: $\mathrm{RCOOH} \xrightarrow{\mathrm{LiAlH}_4} \mathrm{RCH}_2\mathrm{OH}$. Decarboxylation: $\mathrm{RCOONa} \xrightarrow{\mathrm{NaOH}/\mathrm{CaO}, \Delta} \mathrm{RH}$. Hell-Volhard-Zelinsky (HVZ) Reaction: $\mathrm{RCH}_2\mathrm{COOH} \xrightarrow{\mathrm{X}_2/\text{red P}} \mathrm{RCH(X)COOH}$. Amines Preparation Reduction of nitro compounds: $\mathrm{RNO}_2 \xrightarrow{\mathrm{Sn}/\mathrm{HCl} \text{ or } \mathrm{Fe}/\mathrm{HCl} \text{ or } \mathrm{H}_2/\mathrm{Pd}} \mathrm{RNH}_2$. Ammonolysis of alkyl halides: $\mathrm{RX} + \mathrm{NH}_3 \to \mathrm{RNH}_2 \to \mathrm{R}_2\mathrm{NH} \to \mathrm{R}_3\mathrm{N} \to \mathrm{R}_4\mathrm{N}^+\mathrm{X}^-$. Gabriel Phthalimide Synthesis: For $1^\circ$ aliphatic amines. Phthalimide $\xrightarrow{\mathrm{KOH}} \text{Potassium phthalimide} \xrightarrow{\mathrm{RX}} \text{N-alkyl phthalimide} \xrightarrow{\mathrm{H}_2\mathrm{O}/\mathrm{OH}^- \text{ or } \mathrm{N}_2\mathrm{H}_4} \mathrm{RNH}_2$. Hoffmann Bromamide Degradation: $\mathrm{RCONH}_2 + \mathrm{Br}_2 + 4\mathrm{NaOH} \to \mathrm{RNH}_2 + \mathrm{Na}_2\mathrm{CO}_3 + 2\mathrm{NaBr} + 2\mathrm{H}_2\mathrm{O}$ (one carbon less). Reduction of nitriles: $\mathrm{RCN} \xrightarrow{\mathrm{LiAlH}_4 \text{ or } \mathrm{H}_2/\mathrm{Ni}} \mathrm{RCH}_2\mathrm{NH}_2$. Reduction of amides: $\mathrm{RCONH}_2 \xrightarrow{\mathrm{LiAlH}_4} \mathrm{RCH}_2\mathrm{NH}_2$. Reactions Basicity: (See GOC section). Acylation: $\mathrm{RNH}_2 + \mathrm{R'COCl} \to \mathrm{RNHCOR'} + \mathrm{HCl}$. Carbylamine Reaction (Isocyanide Test): $1^\circ$ amine $\xrightarrow{\mathrm{CHCl}_3/\mathrm{KOH}, \Delta} \mathrm{RNC}$ (foul smelling). Reaction with Nitrous Acid ($\mathrm{HNO}_2$): $1^\circ$ aliphatic amine $\xrightarrow{\mathrm{NaNO}_2/\mathrm{HCl}} \text{Diazonium salt} \to \text{Alcohols}$ (with $\mathrm{N}_2$ gas evolution). $1^\circ$ aromatic amine $\xrightarrow{\mathrm{NaNO}_2/\mathrm{HCl}, 0-5^\circ\mathrm{C}} \text{Arenediazonium salt}$ (stable below $5^\circ\mathrm{C}$). $2^\circ$ amine $\to \text{N-nitrosoamine}$ (yellow oily). $3^\circ$ aliphatic amine $\to \text{soluble salt}$. $3^\circ$ aromatic amine $\to \text{p-nitroso compound}$. Hinsberg Test: Distinguishes $1^\circ, 2^\circ, 3^\circ$ amines using benzenesulfonyl chloride ($\mathrm{C_6H_5SO_2Cl}$). $1^\circ$ amine: Product soluble in $\mathrm{KOH}$. $2^\circ$ amine: Product insoluble in $\mathrm{KOH}$. $3^\circ$ amine: No reaction. Electrophilic Substitution on Aniline: Amino group is highly activating, o,p-directing. Bromination: Aniline $\xrightarrow{\mathrm{Br}_2/\mathrm{H}_2\mathrm{O}} \text{2,4,6-tribromoaniline}$. To get mono-substituted product, protect $\mathrm{NH}_2$ group by acetylation (e.g., with acetic anhydride). Nitration: Direct nitration gives tarry products and meta product due to anilinium ion formation. Protect $\mathrm{NH}_2$ first. Sulfonation: Aniline $\xrightarrow{\text{conc. }\mathrm{H}_2\mathrm{SO}_4} \text{Anilinium hydrogen sulfate} \xrightarrow{\Delta} \text{Sulfanilic acid}$ (zwitterionic). Biomolecules Carbohydrates Monosaccharides: Glucose, Fructose. Glucose: Aldohexose. Anomers ($\alpha/\beta$), epimers (at $\mathrm{C}_2$, $\mathrm{C}_4$). Forms hemiacetal ring (pyranose). Open chain form: CHO-(CHOH)4-CH2OH. Fructose: Ketohexose. Forms hemiketal ring (furanose). Reducing sugars: Have free aldehyde/ketone group (e.g., glucose, fructose, maltose, lactose). Reduce Tollens' and Fehling's reagents. Disaccharides: Sucrose, Maltose, Lactose. Sucrose: Glucose + Fructose, non-reducing. Linkage: $\alpha$-D-Glucopyranosyl-$\beta$-D-Fructofuranoside. Maltose: Glucose + Glucose, reducing. Linkage: $\alpha$-1,4-glycosidic. Lactose: Galactose + Glucose, reducing. Linkage: $\beta$-1,4-glycosidic. Polysaccharides: Starch, Cellulose, Glycogen. Starch: Amylose ($\alpha$-1,4-glycosidic) + Amylopectin ($\alpha$-1,4- and $\alpha$-1,6-glycosidic). Cellulose: $\beta$-1,4-glycosidic linkages. Proteins Amino acids: Building blocks. Amphoteric nature (zwitterions). Essential amino acids: Cannot be synthesized by body. Isoelectric point (pI): pH at which amino acid has no net charge. Peptide bond: $-\mathrm{CONH}-$ linkage. Example: $\mathrm{R-CH(NH_2)-COOH} + \mathrm{R'-CH(NH_2)-COOH} \to \mathrm{R-CH(NH_2)-CO-NH-CH(R')-COOH} + \mathrm{H}_2\mathrm{O}$. Structure: Primary: Sequence of amino acids. Secondary: $\alpha$-helix, $\beta$-pleated sheet (H-bonding). Tertiary: 3D folding (disulfide bonds, H-bonds, ionic, hydrophobic). Quaternary: Arrangement of multiple polypeptide units. Denaturation: Loss of biological activity due to change in $2^\circ, 3^\circ, 4^\circ$ structures (heat, pH change). Enzymes Biochemical catalysts that accelerate the rate of biochemical reactions. All enzymes are proteins (except ribozymes). Specificity: Highly specific for their substrate and reaction type. Absolute specificity: Acts on only one substrate. Group specificity: Acts on structurally similar substrates. Stereochemical specificity: Acts on specific stereoisomers. Mechanism of Action: Enzymes bind to specific substrates at their active site to form an enzyme-substrate (ES) complex. Lower the activation energy of the reaction. Lock and Key Model: Substrate (key) fits perfectly into the active site (lock). Induced Fit Model: Active site changes shape slightly to accommodate the substrate. Factors Affecting Enzyme Activity: Temperature: Optimal temperature (e.g., human body temp $37^\circ\mathrm{C}$). High temp denatures enzymes. pH: Optimal pH (e.g., Pepsin pH 1.5-2.5, Trypsin pH 8.5). Extreme pH denatures enzymes. Substrate Concentration: Activity increases with substrate concentration until saturation. Enzyme Concentration: Activity is directly proportional to enzyme concentration. Inhibitors: Molecules that reduce enzyme activity. Competitive: Bind to active site, resemble substrate. Non-competitive: Bind to allosteric site, change active site shape. Classification (based on reaction type): Oxidoreductases: Catalyze redox reactions. Transferases: Transfer a group from one molecule to another. Hydrolases: Catalyze hydrolysis reactions. Lyases: Catalyze removal of groups without hydrolysis, forming double bonds. Isomerases: Catalyze isomerization reactions. Ligases: Catalyze joining of two molecules. Vitamins Fat-soluble: A, D, E, K. Water-soluble: B complex, C. Deficiency diseases (e.g., Vit A $\to$ night blindness, Vit C $\to$ scurvy). Nucleic Acids DNA: Deoxyribonucleic acid. Double helix. Bases: A, T, G, C. Sugar: Deoxyribose. Phosphate. RNA: Ribonucleic acid. Single strand. Bases: A, U, G, C. Sugar: Ribose. Phosphate. Complementary base pairing: A-T (DNA), A-U (RNA), G-C. Practical Organic Chemistry Qualitative Analysis Detection of Elements: Lassaigne's Test: For N, S, Halogens. Organic compound fused with $\mathrm{Na}$. Nitrogen: Prussian blue color with $\mathrm{FeSO}_4$ (due to $\mathrm{Na}_4[\mathrm{Fe}(\mathrm{CN})_6]$). Sulfur: Blood red color with $\mathrm{FeCl}_3$ (if N present, due to $\mathrm{Fe}(\mathrm{CNS})^+$). Violet color with $\mathrm{Na}_2[\mathrm{Fe}(\mathrm{CN})_5\mathrm{NO}]$ (due to $\mathrm{Na}_4[\mathrm{Fe}(\mathrm{CN})_5\mathrm{NOS}]$). Halogens: White/yellow ppt with $\mathrm{AgNO}_3$. $\mathrm{AgCl}$ (white, soluble in $\mathrm{NH}_4\mathrm{OH}$), $\mathrm{AgBr}$ (pale yellow, sparingly soluble), $\mathrm{AgI}$ (yellow, insoluble). Functional Group Tests: Alcohols: Lucas test ($1^\circ, 2^\circ, 3^\circ$), Ceric ammonium nitrate test (red color). Phenols: Neutral $\mathrm{FeCl}_3$ test (violet/blue/green color). Aldehydes: Tollens' reagent (silver mirror), Fehling's solution (red ppt), Schiff's reagent (pink/magenta). Ketones: 2,4-DNP test (yellow/orange ppt). Carboxylic acids: Bicarbonate test ($\mathrm{CO}_2$ effervescence). Amines: Carbylamine test ($1^\circ$), Hinsberg test. Unsaturation: Baeyer's test (disappearance of purple color of $\mathrm{KMnO}_4$), Bromine water test (decolorization). Quantitative Analysis Liebig's method (C, H). Dumas method (N). Kjeldahl's method (N, not for nitro, azo, or N in ring). Carius method (Halogens, S). Phosphorus (magnesium pyrophosphate). Purification Methods Distillation (simple, fractional, vacuum, steam). Crystallization. Sublimation. Chromatography (column, thin layer, paper, gas). Differential Extraction.