If SOCl2 reacts with alcohols via SNi, why doesn't POCl3?

The reaction with SOCl2$\mathrm{S}\mathrm{O}\mathrm{C}\mathrm{l}{\phantom{X}}_2$ is also used instead of PCl3$\mathrm{P}\mathrm{C}\mathrm{l}{\phantom{X}}_3$ and PCl5$\mathrm{P}\mathrm{C}\mathrm{l}{\phantom{X}}_5$ when retention of stereochemistry is required. Phosphorus trichloride and phosphorus pentachloride both lead to inversion.

The mechanism proceeds via a SNi$\mathrm{S}{\mathrm{N}}_{\mathrm{i}}$ pathway, or internal nucleophilic substitution. This step has been highlighed in red; an intimate ion pair[see below]${}^{[\text{see below}]}$ is given in square brackets. Adding a nucleophilic solvent such as pyridine considerably increases inversion with SOCl2$\mathrm{S}\mathrm{O}\mathrm{C}\mathrm{l}{\phantom{X}}_2$ via an attack at the sulfur atom. Green marks blocking of the intramolecular substitution; blue is for inversion.

Reagent :Thionyl Chloride, SOCl2

Thionyl Chloride, SOCl₂

In a blatant plug for the Reagent Guide and the Reagents App for iPhone, each Friday  I profile a different reagent that is commonly encountered in Org 1/ Org 2. 

If there’s one thing you learn how to do well in Org 1, it’s make alcohols. Let’s count the ways: hydroboration, acid-catalyzed hydration, oxymercuration for starters, and then substitution of alkyl halides with water or HO(–). If you want to extend it even further, there’s dihydroxylation (to make diols) using OsO4 or cold KMnO4, and even opening of epoxides under acidic or basic conditions to give alcohols.

There’s just one issue here and it comes up once you try to use alcohols in synthesis. Let’s say you want to use that alcohol in a subsequent substitution step, getting rid of the HO(–) and replacing it with something else. See any problems with that? Remember that good leaving groups are weak bases – and the hydroxide ion, being a strong base, tends to be a pretty bad leaving group.

So what can we do?

Conversion Of Alcohols To Alkyl Halides

What you want to do is convert the alcohol into a better leaving group.  One way is to convert the alcohol into a sulfonate ester – we talked about that with TsCl and MsCl. Today I’m going to talk about a second approach: converting alcohols into alkyl chlorides with thionyl chloride (SOCl2). This is a useful reaction, because the resulting alkyl halides are versatile compounds that can be converted into many compounds that are not directly accessible from the alcohol itself.

If you take an alcohol and add thionyl chloride, it will be converted into an alkyl chloride. The byproducts here are hydrochloric acid (HCl) and sulfur dioxide (SO2).
[NOTE added later: there are significant differences in how this reaction is taught at different schools. Consult your instructor to be 100% sure that this applies to your course]. See post here

There’s one important thing to note here: see the stereochemistry? It’s been inverted.*(white lie alert – see below) That’s an important difference between SOCl2 and TsCl, which leaves the stereochemistry alone. We’ll get to the root cause of that in a moment, but in the meantime, can you think of a mechanism which results in inversion of configuration at carbon?

Conversion Of Carboxylic Acids To Acid Chlorides

As an extra bonus, thionyl chloride will also convert carboxylic acids into acid chlorides (“acyl chlorides”). Like alcohols, carboxylic acids have their limitations as reactants: the hydroxyl group interferes with many of the reactions we learn for nucleophilic acyl substitution (among others). Conversion of the OH into Cl solves this problem.

So how does it work?

Alcohols To Alkyl Chlorides With SOCl₂ – The Mechanism

As you might have guessed, conversion of alcohols to alkyl halides proceeds through a substitution reaction – specifically, an SN2 mechanism. The first step is attack of the oxygen upon the sulfur of SOCl2, which results in displacement of chloride ion. This has the side benefit of converting the alcohol into a good leaving group: in the next step, chloride ion attacks the carbon in SN2 fashion, resulting in cleavage of the C–O bond with inversion of configuration. The HOSCl breaks down into HCl and sulfur dioxide gas, which bubbles away.

Carboxylic Acids To Acid Chlorides With SOCl₂ – The Mechanism

The mechanism for formation of acid chlorides from carboxylic acids is similar.