Reactions of Alcohols

Reactions of Alcohols • Formation of Tosylate Esters • The carbinol carbon of an alcohol is electrophilic; however, the OH- ion is a poor leaving group • The hydroxyl group can be converted to the tosylate ester, which acts as a very good leaving group.

Reactions of Alcohols • Formation of Tosylate Esters • Conditions: • TsCl • pyridine p-toluenesulfonyl chloride tosyl chloride, TsCl tosylate ester ROTs = pyridine

Reactions of Alcohols • Substitution and Elimination Reactions of Tosylate Esters • Since the tosylate ion is a good leaving group, tosylate esters undergo substitution and elimination reactions: E2 and SN2 reactions most useful synthetically…no rearrangements

Reactions of Alcohols Example: Predict the major product of each of the following reactions:

Reactions of Alcohols • Esterification of Alcohols • formation of an ester from an alcohol and a carboxylic acid or acid chloride • Formation of ester from the carboxylic acid is an equilibrium process: • drive reaction to the right by • removing water as formed • using large excess of acid or alcohol ester

Reactions of Alcohols • Esterification of Alcohols • Formation of ester from the acid chloride is not an equilibrium process ester

Reactions of Alcohols Example: Predict the product formed in each of the following reactions:

Reactions of Alcohols • Formation of Nitrate, Sulfate and Phosphate Esters • common inorganic acids such as nitric acid, sulfuric acid, and phosphoric acid form esters with alcohols glycerol glycerine nitroglycerine explosive

Reactions of Alcohols • Phosphate ester linkages are found in the backbone of the nucleic acids, RNA and DNA.

Reactions of Alcohols • Formation of Alkyl Halides • Best Reagents: • HBr or PBr3 produces RBr • SOCl2 or ZnCl2/HCl produces RCl • P/I2 producesRI • The reagent of choice depends on the type of alcohol used.

Reactions of Alcohols • Summary of Best Reagents for ROH RX * works only with selected alcohols of this type

Reactions of Alcohols • Reaction of Alcohols with HBr • 1o alcohols react via an SN2 mechanism • 2o and 3o alcohols react via an SN1 mechanism

Reactions of Alcohols • Reaction of Alcohols with HCl • similar mechanisms (SN1 and SN2) as with HBr • Chloride ion is weak nucleophile • ZnCl2 is added to promote the reaction of HCl with primary and secondary alcohols • ZnCl2 complexes with the oxygen of the OH group and makes it a better leaving group (CH3)2CHOH (CH3)2CHCl HCl (aq) ZnCl2

Reactions of Alcohols • Disadvantages of using HX to convert alcohols to alkyl halides • elimination competes with substitution • alkene formed • rearranged products may form with secondary alcohols • poor yields of 1o and 2o alkyl chlorides • Most alcohols give poor yields of the alkyl iodides when reacted with HI

Reactions of Alcohols • Reactions of Alcohols with PBr3 • for producing 1o and 2o alkyl bromides • poor yields with 3o alcohols

Reactions of Alcohols • Reactions of Alcohols with P/I2 • PI3 is unstable so P/I2 is used to generate PI3 “in situ” • best reagent for converting 1o or 2o alcohols to the corresponding alkyl iodide CH3(CH2)14CH2OH CH3(CH2)14CH2I P/I2

Reactions of Alcohols • Reactions of Alcohols with SOCl2 • Thionyl chloride (SOCl2) is the preferred reagent for producing alkyl chlorides

Reactions of Alcohols Example: Predict the product for each of the following reactions.

Reactions of Diols • Pinacol Rearrangement • dehydration of a tertiary 1,2-diol and subsequent rearrangement of the carbonium ion intermediate to form a ketone

Reactions of Diols • Mechanism of Pinacol Rearrangment

Reactions of Diols • Periodic Acid Cleavage of Diols • formation of aldehydes and/or ketones from glycols (1,2-diols) • forms same product as O3 followed by (CH3)2S

Reactions of Diols • Example:

Reactions of Alcohols Example: Propose a reasonable multistep synthetic route for the following conversions:

Reactions of Alcohols