Comprehensive University Study Notes on Organic Chemistry: Haloalkanes, Carbonyls, Hydroxyls, and Carboxylic Derivatives

Haloalkanes and Alkylene Halides

• General Formula and Classification

  • Haloalkanes, also known as alkyl halides, have the general formula $C_nH_{2n+1}X$.
  • The halogen variable $X$ represents fluorine ($F$), chlorine ($Cl$), bromine ($Br$), or iodine ($I$).
  • In chemical studies, alkyl fluorides are considered separately because they do not follow the same trends as other alkyl halides.

• Methods of Preparation

  • Halogenation of Hydrocarbons: Alkanes are halogenated using light as a catalyst. This process is primarily used for preparing methyl halides but has limited preparative importance otherwise due to the risk of multiple substitution. The issue of multiple substitution is less prevalent with bromination than with chlorination. This process cannot be used for iodine.
  • From Alkenes: Alkenes add hydrogen halides ($HX$) to form alkyl halides, a reaction that follows Markownikoff’s rule.
  • From Grignard Reagents: The reaction of a Grignard reagent with a halogen yields an alkyl halide.

• Physical Properties

  • Lower members of the series are colourless gases.
  • While alkyl halides are colourless in their pure state, small amounts of decomposition upon exposure to light cause iodides to develop a red or brown coloration.
  • Lower members possess a sweetish smell and burn with green-edged flames.
  • They are almost insoluble in water but dissolve readily in ether and alcohol.

• Chemical Properties

  • Alkyl halides serve as vital reagents in organic synthesis because the halogen can be easily replaced in displacement reactions by nucleophiles (groups with lone pairs or negative charges), leading to aliphatic nucleophilic substitution reactions.
  • Reactions with Reactive Metals: They react with reactive metals to yield alkanes. Divalent metals produce organometallic compounds.
  • Reduction: Iodides, tertiary chlorides, and bromides are reduced to alkanes in the presence of a catalyst.
  • Ethanolic Potassium Hydroxide: Boiling alkyl halides with ethanolic potassium hydroxide ($KOH$) results in an elimination reaction to yield alkenes.
  • Ester Formation: Alkyl halides react with salts of acids to form certain esters.
  • Ether Formation: Heating alkyl halides with sodium ethoxide produces ethers.
  • Reaction with Alcoholic $AgNO_3$: Warmed alcoholic silver nitrate solution causes the slow precipitation of silver halide. The rate of precipitation follows the order: $benzyl, alkyl, 3^\text{o} > 2^\text{o} > 1^\text{o}$.

• Alkylene Halides

  • The halogen can be linked either directly to a double-bonded carbon or to a carbon containing a double bond.
  • Vinyl Halides: Examples include chloroethene (vinyl chloride, $CH_2=CHCl$). The halogen in vinyl halides is unreactive and does not undergo standard substitution reactions common to alkyl chlorides.
  • Allyl Halides: Examples include 3-chloro-1-propene (allyl chloride, $CH_2=CH-CH_2Cl$). The halogen is as mobile as in alkyl halides, allowing groups like $-OH$, $-NH_3$, and $-CN$ to replace it. Allyl chloride is a key starting material for synthesizing allyl derivatives.
  • Preparation of Vinyl Chloride: Prepared by heating dichloro- or dibromoethane with ethanolic potassium hydroxide or tertiary amines as a base. It can also be obtained by adding hydrogen chloride to ethyne.
  • Preparation of Allyl Halides: Prepared using methods similar to those for alkyl halides.

Aldehydes and Ketones

• Structural Definitions

  • These compounds contain the carbonyl functional group ($>C=O$).
  • Aldehyde: The carbonyl group is located on the terminal carbon atom.
  • Ketone: The carbonyl group is not on the terminal carbon but is attached to two other atoms.

• Nomenclature

  • Aldehydes: Common names replace "-oic acid" with "aldehyde." IUPAC names replace the "-ne" suffix of the parent alkane with "-nal."
  • Ketones: The trivial system names the two groups attached to the carbonyl followed by the word "ketone" (e.g., $CH_3CH_2COCH_3$ is methyl ethyl ketone; $CH_3CH(CH_3)COCH_3$ is methyl isopropyl ketone). IUPAC names find the longest chain including the carbonyl group, use numbers for position, and replace the "-e" suffix with "-one" (e.g., $butan-2-one$).
  • Aromatic Ketones: Examples include acetophenone ($C_6H_5COCH_3$) and benzophenone ($C_6H_5COC_6H_5$).

• Methods of Preparation: Aliphatic Aldehydes

  • Oxidation of Primary Alcohols: Yields aldehydes as initial products. Because aldehydes are more susceptible to oxidation than parent alcohols, the reaction is performed at temperatures where the aldehyde distils off (lower boiling points as they lack hydrogen bonding).
  • Calcium Salts: Reduction occurs by distilling a mixture of the calcium salt of methanoic acid and other carboxylic acids. Alternatively, passing vapours of the free acids over titanium oxide at $300-330^\text{o}C$ or over zinc dust at $300^\text{o}C$ yields the aldehyde.
  • Rosenmund Reduction: Treatment of acid chlorides with hydrogen using a palladium-on-barium-sulphate catalyst. Barium sulphate acts as a poison to prevent further reduction to alcohol. The reaction often occurs in boiling xylene with sulphur and quinolone as extra catalyst poisons.
  • Grignard Reagent: Yields aldehydes when reacted with a methanoic acid ester in a $1:1$ mole ratio. The Grignard must be added to the ester to avoid forming secondary alcohols. Hydrogen cyanide ($HCN$) also reacts with Grignard reagents to yield aldehydes.

• Methods of Preparation: Aromatic Aldehydes

  • Oxidation of Methyl Benzenes: Using chromium trioxide in acetic anhydride converts the formed benzaldehyde to benzylidene acetate, preventing further oxidation. Subsequent hydrolysis with dilute $HCl$ or $H_2SO_4$ yields benzaldehyde.
  • Catalytic Oxidation: Methyl benzene is oxidized using air diluted with nitrogen at $500^\text{o}C$ using oxides of manganese, molybdenum, or zirconium.
  • Gattermann-Koch Reaction: Bubbling carbon (II) oxide and hydrogen through a solution containing benzene and copper (I) chloride in nitrobenzene or ether.

• Methods of Preparation: Ketones

  • Oxidation of Secondary Alcohols: Reagents include acidified dichromate, potassium permanganate, or aluminum t-butoxide with acetone (Oppernauer oxidation).
  • Monocarboxylic Acids: Heating barium, calcium, or iron salts of acids (other than methanoic) yields ketones. Alternatively, passing acid vapours over manganese (II) oxide at $300^\text{o}C$. Dicarboxylic acids distilled with barium oxide yield cyclic ketones.
  • Ozonolysis of Alkenes: Alkenes of type $R_1R_2C=CR_2$ yield ketones or aldehyde-ketone mixtures.
  • Grignard Reagent: Reaction with alkyl cyanide followed by hydrolysis or with acyl chloride (using a $1:1$ ratio; adding Grignard to acyl chloride to avoid tertiary alcohols).
  • Malonic Ester: Hydrolysis and decarboxylation of alkyl malonic esters yield ketones.
  • Friedel-Crafts Acylation: Reaction of benzene with acyl chlorides using aluminum chloride ($AlCl_3$) catalyst to yield aromatic ketones.

• Physical and Chemical Properties

  • Physical States: Methanal is a gas with an unpleasant smell. Higher aldehydes are liquids, becoming fruitier with longer chains. Lower ketones are liquids; those with up to four carbons are water-soluble. Higher ketones can have flower-like or rancid smells.
  • Reactivity Site: The carbonyl group is a site for nucleophilic attack due to electronegativity differences. It also increases the acidity of the hydrogen on the alpha carbon, allowing strong bases to form carbanions.
  • Meerwin-Pondorf-Verley Reduction: Aldehydes/ketones heated with aluminum isopropoxide in isopropanol solution are reduced to alcohols. Specific to the carbonyl group; does not affect double bonds or nitro groups.
  • Clemmensen Reduction: Carbonyls (usually ketones) reduced to hydrocarbons by zinc amalgam in concentrated $HCl$.
  • Wolf Kishner Reduction: Used for acid-sensitive groups; uses hydrazine in the presence of a base.
  • Oxidation Differences: Aldehydes are easily oxidized to carboxylic acids by mild agents ($Cu^{2+}$ in Fehling's/Benedict's, or $Ag^+$ in Tollen's reagent). Only aliphatic aldehydes give a positive Benedict's test. Ketones require vigorous oxidation, leading to C-C bond cleavage.

• Addition Reactions

  • Water: Forms unstable hydrates in acidified aqueous solution.
  • Alcohol: Aldehydes form acetals in the presence of anhydrous mineral acid, removing water as an azeotrope. Acetals are stable to bases but easily cleaved by acids. Ketones form ketals via ethylorthoformate.
  • Grignard Reagent: Methanal yields primary alcohols; other aldehydes yield secondary alcohols; ketones yield tertiary alcohols.
  • Sodium Bisulphite: Forms crystalline adducts. Useful for separating aldehydes from impurities as they are water-soluble but ether-insoluble and can regenerate the original aldehyde via heating.
  • Hydrogen Cyanide: Forms cyanohydrins. Acidity must be controlled as high acidity retards the reaction. Hydrolysis of cyanohydrins yields unsaturated or alpha-hydroxyl carboxylic acids.

• Aldol Condensation

  • Aldehydes with an alpha-hydrogen condense in dilute alkali. A carbanion of one molecule adds to the carbonyl of a second to form an aldol. If two different aldehydes with alpha-hydrogens are used, a mixture of four products results.

• Tests for Carbonyl Compounds

  • General: Reaction with 2,4-dinitrophenyl hydrazine yields insoluble red or yellow hydrazones.
  • Aldehyde Differentiation: Color changes with $KMnO_4$ (purple to colourless) or $K_2Cr_2O_7$ (orange to green). Positive Tollen’s, Fehling’s, and Schiff’s reagent (magenta colour). Methyl ketones give a positive iodoform test.

Hydroxyl Compounds (Alcohols)

• Classification and Occurrence

  • Monohydric alcohols have the formula $C_nH_{2n+1}OH$.
  • Classification: Primary ($RCH_2OH$), Secondary ($R_1RCH-OH$), Tertiary ($R_{11}R_1RC-OH$).
  • Simplest alcohol is methanol (methyl alcohol or carbinol).

• Industrial Preparation

  • Ethanol via Fermentation: Starch to sugar, then fermented by yeast. Distillation leaves "mash" for cattle fodder. Fractional distillation yields $90-95\%$ ethanol and "fusel alcohol" ($1-propanol, 2-butanol, 2-methyl-1-butanol$). Water removal involves boiling with quicklime or azeotropic distillation with benzene ($azeotrope B.P. 65.85^\text{o}C$; absolute ethanol distils at $78.3^\text{o}C$).
  • Ethylene Hydration: Direct water addition or sulphuric acid addition followed by hydrolysis of alkenes.
  • Methanol (Coal): Destructive distillation of wood yields pyroligeneous acid (ethanoic acid, acetone, methanol). Acetic acid is fixed with $Ca(OH)_2$ as calcium ethanoate before fractional distillation.
  • Methanol (Catalytic): Reducing $CO$ with $H_2$ at $450^\text{o}C$ and $200$ atm using zinc/chromium oxide catalysts.

• Laboratory Preparation

  • Hydrolysis: Alkyl halides or esters heated with water, acids, or alkalis.
  • Grignard Reagent: Reaction with aldehydes/ketones/ethylene oxide. Ethylene oxide and methanal yield primary alcohols; other aldehydes yield secondary; ketones/esters yield tertiary.
  • Reduction: Bouveault-Blanc reduction uses sodium in ethanol. Lithium aluminum hydride ($LiAlH_4$) in ether reduces many groups but not C=C. Sodium borohydride ($NaBH_4$) in ethanol reduces aldehydes/ketones only and has no effect on acids/esters.

• Physical Properties

  • Colourless neutral compounds with burning tastes. Solubility decreases with mass ($C_1$ to $C_3$ are miscible). Melting/boiling points increase with mass.
  • Methanol is a powerful intoxicant and poison causing blindness and death.

• Chemical Reactions

  • C-OH Bond Break: Reactivity order: $allyl, benzyl > 3^\text{o} > 2^\text{o} > 1^\text{o}, CH_3$. Includes reactions with $HX$ (often $S_N1$), phosphorus trihalides, and dehydration to alkenes (using heat, alumina, or conc. $H_2SO_4$).
  • CO-H Bond Break (Acidic Reaction): Reactivity order: $1^\text{o} > 2^\text{o} > 3^\text{o}$. Includes reactions with active metals ($Na, K, Mg, Al$) to form alkoxides and $H_2$. Alcohols are usually weaker acids than water but stronger than ammonia and ethyne. Esterification with organic acids is catalysed by conc. $H_2SO_4$ or dry $HCl$.
  • Oxidation: Primary yield aldehydes/acids; secondary yield ketones (can be pushed to acid cleavage with hot $KMnO_4$); tertiary are resistant except to strong agents that cause C-C cleavage. Oppernauer oxidation uses aluminum t-butoxide for secondary to ketones.

• Tests for Alcohols

  • Lucas Reagent ($HCl + ZnCl_2$): $3^\text{o}$ reacts immediately (cloudiness); $2^\text{o}$ reacts in $5$ minutes; $1^\text{o}$ does not react at room temperature.
  • Iodoform Test: Identifies a methyl group on the carbon bearing the $-OH$ group.
  • Copper Oxidation ($300^\text{o}C$): $1^\text{o} \rightarrow$ aldehydes; $2^\text{o} \rightarrow$ ketones; $3^\text{o} \rightarrow$ alkenes.

Phenols

• Structure and Preparation

  • Aromatic alcohols with $-OH$ directly on the ring. Found in coal tar (middle oil fraction).
  • From Aromatic Halides: Heating with $8\%$ aqueous $NaOH$ and copper salts at high temperature.
  • From Amines: Conversion to diazonium salts and boiling in water (or using boiling $CuSO_4$ for complex salts).
  • Fusion: Fusing aromatic sulphonic acids with alkalis.
  • Arylthallium Compounds: Benzene reacted with thallium trifluoroacetate, then lead tetraacetate and tryphenylphosphine, followed by hydrolysis.

• Properties and Reactions

  • Phenol is a colourless crystalline solid ($m.pt 43^\text{o}C, b.pt 182^\text{o}C$), turning pink upon oxidation. Used as an antiseptic (carbolic acid) and in Bakelite synthesis.
  • Acidity: Stronger acids than alcohols due to resonance stabilization of the phenoxide ion and electron shift. Electron-withdrawing groups (like nitro) increase acidity ($2,4,6-trinitrophenol$ is as acidic as carboxylic acids); electron-donating groups decrease it.
  • Oxidation: yielding catechols or quinones; often results in complex mixtures.
  • Iron (III) Chloride Test: Enols like phenol give colored complexes (phenol gives violet).
  • Libermann’s Reaction: Coloration with potassium nitrite in concentrated $H_2SO_4$.
  • Ring Substitution: $-OH$ is a ring activator directing to ortho/para positions. Kolbe reaction adds a carboxylic group using $CO_2$. Condensation with formaldehyde forms Bakelite resins.

Carboxylic Acids

• Nomenclature and Physical Properties

  • General formula suffix is "-oic." Formic acid ($HCOOH$) is methanoic; Acetic acid ($CH_3COOH$) is ethanoic; Propionic acid ($CH_3CH_2COOH$) is propanoic.
  • Higher boiling points due to hydrogen bonding. Solubility decreases with size; melting points follow an odd-even trend.

• Preparation

  • Oxidation: Primary alcohols/aldehydes $\rightarrow$ acids; ketones require vigorous conditions (C-C break).
  • Nitrile Hydrolysis: Alkyl halides reacted with $NaCN/KCN$ then hydrolysed; gains one carbon.
  • Alkyl Benzenes: Side chain oxidation using hot $KMnO_4$.
  • Carbonation: Grignard reagent reacted with solid $CO_2$ (dry ice).
  • Alkenes: Heating with $CO$ and steam at $300-400^\text{o}C$ (catalyst: $H_3PO_4$) or via ozonolysis.

• Acidity and Chemical Properties

  • Weak acids but stronger than alcohols/phenols due to resonance. Salt formation with bases; liberates $CO_2$ from $NaHCO_3$.
  • Nucleophilic Substitution: Forms esters with alcohols, acid chlorides with $PCl_5$ or $SOCl_2$, and amides via acid chlorides.
  • Reduction: Resistant to reduction; requires $LiAlH_4$ or high-pressure $H_2$ with catalysts.
  • Decarboxylation: Heating sodium salts with sodalime yields alkanes.
  • Dicarboxylic Acids: Saturated acids with odd carbon numbers have lower melting points and higher solubility than even-numbered ones. Heating oxalic/malonic acids liberates $CO_2$; succinic/phthalic acids form cyclic anhydrides.

Esters and Nitrogen Compounds

• Esters

  • Naming replaces "-oic acid" with "-ate" (e.g., ethyl ethanoate). Produced via esterification, acid chloride alcoholysis, or using diazomethane for methyl esters.
  • Hydrolysis: Alkaline hydrolysis (saponification) forms soaps (metal salts of fatty acids) and glycerol. Soaps form micelles with hydrophobic heads inward; they fail in hard water ($Ca^{2+}/Mg^{2+}$). Detergents (from hydrogenolysis of fats then sulphonation) work in hard water.
  • Transesterification: Cleavage by alcohol, catalysed by $H_2SO_4$ or alkoxide.

• Amines

  • Alkyl-substituted ammonia. Classification: Primary ($RNH_2$), Secondary ($R_2NH$), Tertiary ($R_3N$), Quaternary ($R_4N^+$).
  • Preparation: Hofmann method (alkyl halide + $NH_3$), reduction of nitro/cyanides, Hoffmann degradation (amide to primary amine with one fewer carbon).
  • Tests: Primary amines give the Carbylamine test (unpleasant smell) and Mustard oil test ($isothiocyanate$). Secondary amines form yellow/brown nitrosoamines with nitrous acid. Tertiary amines are mostly inert to nitrous acid.

• Amides

  • Formula $R-CONR_1R_2$. Prepared by heating ammonium salts of acids or ammonolysis of esters/chlorides. Hydrolysis (acid/base) yields acids and ammonia/amines. Dehydration with $PCl_5$ yields alkyl cyanides.