Preparation of Alkyl Halides and Tosylates from Alcohols

In alcohols, the -OH can be "activated" wherein it is converted to a better leaving group.

Chlorination, bromination, and tosylation

For example bromination and chlorination with PBr₃ and SOCl₂ respectively occur by a substitution.  Recall that these reagents convert the OH to a better leaving group which is substituted by the Cl^- or Br^- anions.  The displacement is an S_N2 reaction so there's an inversion of stereochemistry that's apparent if the alcohol is chiral.

Tertiary Alcohols

Halogenation of Tertiary (3^o) Alcohols

Tertiary alcohols can be converted to the corresponding chlorides and bromides by using HCl and HBr.  Recall that this proceeds via and SN1 pathway.

1^o and 2^o Alcohols

As we've discussed, the hydroxyl group (-OH) is a poor leaving group, hindering direct substitution reactions at the carbon bearing the -OH group. To effectively convert alcohols to alkyl halides, we need to activate the hydroxyl group, transforming it into a better leaving group.  Both thionyl chloride (SOCl₂) and phosphorus tribromide (PBr₃) are valuable reagents for achieving this. These reactions efficiently converts alcohols to alkyl chlorides and bromides, providing a valuable synthetic tool.

This activation occurs through the formation of an intermediate. With thionyl chloride, this intermediate is a chlorosulfite (-OSOCl), while PBr₃ forms a dibromophosphite (-OPBr₂) intermediate. These intermediates are then susceptible to nucleophilic attack by the corresponding halide ion (chloride or bromide, respectively), which acts as the nucleophile in the SN2 reaction. Because the SN2 mechanism involves a backside attack, both reactions proceed with inversion of stereochemistry at the carbon atom bearing the hydroxyl group.

Chlorination of 1^o and 2^o alcohols

Bromination of 1^o and 2^o alcohols

Tosylation of 1^o and 2^o alcohols

However, in tosylations, the reaction of an alcohol with tosyl chloride does not invert the stereochemistry.  This is a result of the direct reaction of the hydroxyl group O atom with the tosyl chloride.

Dehydration

Dehydration reactions typically occur by way of elimination reactions.  Treating acohols with strong acid in absence of water typically results in eliination

Acid Catalyzed

Typically utilizes concentrated H₂SO₄, H₃PO₄ or pTSA.

This occurs by an E1 elimination.  The -OH is protonated and the water expelled to generate a carbonation.  The carbocation is then deprotonated to form an alkene.  This does not work well for substrates that are sensitive to acid, since the alcohol must be heated in the presences of a strong acid.

POCl₃/Pyridine

POCl3/pyridine is useful for acid sensitive substrates

Recall that the mechanism proceeds as follows.  Notice the E2 elimination in the second step in which pyridine behaves as a base.