Alkyl Halides and Nucleophilic Substitution Summary

Alkyl Halides: Nomenclature and Classification

• IUPAC name for tertiary butyl chloride: 2-chloro-2-methyl propane.
• Isobutyl chloride: primary alkyl halide.
• Secondary and iso-alkyl halide: 2-chlorobutane.

Reactions and Mechanisms

• Alcoholic KOH with $CH<em>3-CH</em>2-CH-CH<em>3$ yields $C</em>4H_8$.
  $Br$
• SN1 mechanism involves formation of carbonium ion.
• $CH<em>3-CH</em>2-OH + SOCl<em>2 \rightarrow CH</em>3CH<em>2Cl + SO</em>2 + HCl$
• Isopropyl chloride undergoes nucleophilic substitution in aqueous solution by both SN1 & SN2 mechanism.
• Reaction of haloalkane with $NH_3$ gives a mixture of 1°, 2°, and 3° amines.
• SN1 reactivity order: CH3X < RCH2X < R2CHX < R3CX
• 2-bromopentane with $C<em>2H</em>5OK$ in ethanol yields 2-pentene.
• $(CH<em>3)</em>3CMgCl + H<em>2O \rightarrow (CH</em>3)_3CH$ (Iso-butane).
• Grignard reagent + $CO_2 \rightarrow$ carbonyl compound.

Elimination Reactions

• Elimination reaction does not show nucleophilic substitution of $C<em>2H</em>5Br$ is $C<em>2H</em>5Br + H<em>2 \rightarrow C</em>2H_6 + HBr$

Ethers and Alcohols

• Alkyl halide + metal alkoxide yields ether (Williamson synthesis).
• $C<em>2H</em>5Cl \xrightarrow{Mg/ether} X \xrightarrow{H<em>2O} Y$ 'Y' is $C</em>2H_6$.
• $CH<em>3MgBr + C</em>2H<em>5CHO \rightarrow CH</em>3CH(OH)C<em>2H</em>5$
• ter-butyl chloride + sodium ethoxide: major product is $(CH<em>3)</em>2C=CH_2$

Nucleophiles and Leaving Groups

• Not a nucleophile: None of These (OH-, OR-, NH2, NH3, Cl- are nucleophiles).
• Best leaving group: $I^-$.

Grignard Reagents

• Ethyl magnesium bromide + $CO_2 \rightarrow$ propanoic acid.
• Grignard reagents react due to the polarity of the R-Mg bond.
• Grignard reagent + alkyl halide produce alkane.

Isomers and Aniline

• Isomeric alkyl halides with molecular formula $C<em>4H</em>9Cl$: 4.
• $CH<em>3-CH</em>2-CH_2-Br \xrightarrow{Alc.KOH} A \xrightarrow{HBr} B$ Product B is: All of These.
• Phenyl amine is also known as aniline.

Factors Affecting SN1 and SN2 Reactions

• Most favorable solvent for SN2 reaction: $CH_3CN$.
• Factors favoring elimination over substitution: Less polar solvent.
• Most nucleophilic: $SH^-$.
• Alkyl halides are highly reactive due to low bond energy of C-X bond.
• SN2 mechanism with an optically active compound yields a racemic mixture.
• Formation of Grignard reagent is a heterogenous reaction.
• Grignard reagent will produce alkane on reacting with all except: alkyl halide.

Reaction Products

• Methyl formate + excess Grignard reagent yields tertiary alcohol.
• $C<em>2H</em>5-Mg-Cl + CO_2 \rightarrow$ Propanoic acid.
• Grignard reagent + ester does not give alcohol
• Iodide ion is a good nucleophile and a good leaving group.
• 1-Chlorobutane + alcoholic potash yields 1-butene.
• Increasing order of reactivity in nucleophilic substitution: CHF > CH3Cl > CH3Br > CH_3I
• SN1 reaction on chiral center leads to partial racemization.
• $CH<em>3-CH</em>2Br + NaCN \rightarrow CH<em>3-CH</em>2CN + NaBr$ is fastest in Dimethyl formamide (DMF).
• Primary alkyl halide prefers SN2 reaction.
• $(CH<em>3)</em>3C-I$ undergoes SN1 reaction most readily.

Elimination vs. Substitution

• Bulky substrate favors elimination over substitution.
• Carbocation intermediate is not involved in: SN2, E2.
• Action of sodium ethoxide on alkyliodide: Nucleophilic substitution.
• Tertiary butyl halide + water follows SN1 mechanism.
• Inversion of configuration supports SN2 mechanism.
• Carbocations undergo all reactions except Rearrangement to form a less stable carbocation.
• Dehydrohalogenation: base abstracts proton on carbon next to the carbon with halogen.
  *Benzyl chloride + aqueous NaOH yields benzyl alcohol.
• $(CH<em>3)</em>3C-Cl$ is a tertiary alkyl halide.

SN1 and SN2

• SN2 is favored by non-polar solvents.
• 2-bromo-3, 3-dimethyl butane + alcoholic KOH gives major product: 2,3-dimethyl-2-butene.
• SN1 reaction rate is independent of nucleophile concentration.
• Electrophilic substitution in phenol occurs at ortho and para-positions.
• 1, 2-H shift, 3° product is the most primary carbocation.
• Reactivity order of alkyl halides: R-I > R-Br > R-Cl > R-F.
• SN2 reaction leads to inversion of configuration.
• In SN1, the added nucleophile plays no kinetic role.
• SN2 reactions: rate depends on concentration of nucleophile and alkyl halide.
• Tertiary alkyl halides are practically inert to SN2 due to steric hindrance.
• Ethyl alcohol is obtained when ethyl chloride is boiled with aqueous KOH.
• SN2: CH3CI shows complete stereochemical inversion.
• Reagent NaCl cannot be used to prepare alkyl halide from alcohol.
• Reactivity order towards elimination: 3°>2°>1°.
• SN2 mechanism proceeds through a transition state.
• SN1 reaction proceeds with 98% racemisation.