organic chemistry: reactions of alcohols , alkyl halides and amines

• alcohols as nucleophiles in S_N2 chemistry

• relatively weak nucleophiles - have to make alkoxide to make it act as a nucleophile

• alkoxides tend to act as bases which leads to elimination reactions but can act as nucleophiles for substitution reactions at sp³ electrophiles

• need good leaving group to act as nucleophiles - C-X bond weak and X- stable anion

alcohols as electrophiles

• hydroxyl group is a bad leaving group - can be converted to better leaving group so that it sustains formation of negative charge

• tosylation of alcohols to form alkyl tosylates - good leaving groups, use tosyl chloride and polar protic solvent

• acylation of alcohols to form alkyl esters - ok leaving groups, use acyl chloride and polar protic solvent

• conversion of alcohols to alkyl halides - use PCl_3, PBr₃, HBr

alkyl halides as electrophiles

• R-X where X = Cl, Br, I are electrophiles

• R’CH₂-X bond is weak and X^- stable as an anion - good leaving group

• alcohols can be converted to alkyl halide via a tosylate - using ionic compound and polar protic solvent

azide and cyanide ions as nucleophiles

• linear, pointy, sterically unhindered, not too basic - good nucleophiles

• CN sp hybridized so has 50% s character - closer to nucleus so more stabilisation of anion

reactions of amines

• N-alkylation of amines - get a mixture of alkylation products as nucleophilic substitution will continue since primary and secondary amines still nucleophilic

• N-acylation with acid halides - amide formation via a tetrahedral intermediate, N in amide not nucleophilic as lone pair delocalised onto O atom

synthesis of amines

• primary amines:

alkyl halide made into alkyl azide using NaN₃ and good nucleophile, alkyl azide made into primary amine using H₂ and Pd-C

alkyl halide made into alkyl cyanide using NaCN and polar aprotic solvent, alkyl cyanide made into primary amine using strong reducing agent - cyanide ion weakly electrophilic so strong reducing agent can reduce it

• secondary amines:

amine (nucleophile) reacted with acyl chloride and polar protic solvent to form amide - weak electrophile so strong reducing agent can reduce it to secondary amine