Leaving Group Conversions - Sulfonyl Chlorides - Online Tutor, Practice Problems & Exam Prep

Alcohols are poor leaving groups in organic reactions, often converted to sulfonate esters, which are excellent leaving groups due to their stability and ability to delocalize negative charge. The conversion involves using sulfonyl chlorides, where the alcohol's oxygen acts as a nucleophile, forming a sulfonate ester while retaining configuration. Common sulfonate esters include mesylate, tosylate, and triflate. This process allows for subsequent nucleophilic attacks, enhancing reaction efficiency in organic synthesis.

Learning the mechanism of Sulfonyl Chlorides.

Alcohols are really bad leaving groups, so we're often in the position where we want to convert the alcohol to a better leaving group. And one of the options that we can use is sulfonate esters. It turns out that sulfonate esters are really the ultimate leaving groups of organic chemistry because they're so extremely stable after they leave. They do an amazing job balancing out that negative charge and delocalizing it. So, how do we turn an alcohol into a sulfonate ester? All we do is we just use the chloride of that sulfonate ester. So we're going to use a sulfonyl chloride to convert the alcohol into a sulfonate ester. And I'll show you guys how to do that in just a second.

First of all, what is a sulfonate ester? Well, if you guys remember, the general structure was just that you had basically an S with 2 double bond O's. S==O=O So I'm just going to draw a line here. And then you had an R group. So a sulfonate ester would have basically an O on this side, =O where the Cl is, then an S, the 2 double one O's and then your R group. Now the identity of the R group is just going to change the name of the sulfonate ester.

In general, all of these different molecules can be categorized as sulfony esters but they do get individual names. So, for example, the simplest situation would just be what if it's just a methyl group? Well, then that's called a mesyl or a mesylate sulfonate ester or mesylate. How about if it's a benzene ring with a methyl group? Well, then that's called a tosyl. So basically, if the R is a benzene and a CH3, then that's a tosylate. And finally, if it's a CF3, so I just replace 3 H's with F's, that's called a triflate.

What is a Sulfonyl Chloride? Well, a Sulfonyl Chloride just means remove the O and put a chlorine right there. SOCl Okay? So, let's just start off with the first step of the mechanism. When my oxygen on the alcohol is considered my nucleophile because it has electrons that are freely able to donate, it will initiate the reaction. If I were to attack one of the atoms on the Sulfonyl Chloride, the sulfur, due to electron pull, creates a partial positive, thus being the most electrophilic. I'm going to move these electrons up to the O, creating a structure with a new bond formation and cleavage that leads to a stable intermediate. Now the next step might involve dealing with the good leaving group, Cl. I could just reform the double bond and kick out the Cl. This will transform the intermediate into a sulfonate ester.

Finally, this is how the sulfonate ester looks: O=S-=OR. Notice how stable this structure is due to no formal charges anymore. We can keep this sulfonate ester around as long as we want, just like an alkyl halide, and then when I finally want to react with it, I could introduce a nucleophile for a backside attack.

This reaction amazingly proceeds with retention of configuration because the oxygen never moves, maintaining its position throughout the reaction. This contrasts reactions with thionyl chloride and phosphorus bromide, which proceed with inversion of configuration during their nucleophilic substitution reactions.

Here’s what students ask on this topic:

What are sulfonate esters and why are they considered good leaving groups in organic chemistry?

Sulfonate esters are compounds where a sulfonyl group (SO₂) is bonded to an oxygen atom, which is further bonded to an organic group (R). They are considered excellent leaving groups because they are highly stable after leaving, due to their ability to delocalize the negative charge over the sulfur and oxygen atoms. This stability makes them very effective in facilitating nucleophilic substitution reactions, enhancing the efficiency of organic synthesis.

How do you convert an alcohol to a sulfonate ester using sulfonyl chlorides?

To convert an alcohol to a sulfonate ester, you react the alcohol with a sulfonyl chloride. The oxygen atom of the alcohol acts as a nucleophile and attacks the sulfur atom of the sulfonyl chloride, forming a bond. This reaction proceeds with the retention of configuration, resulting in the formation of a sulfonate ester. Common sulfonyl chlorides used include mesyl chloride, tosyl chloride, and triflyl chloride, leading to the formation of mesylates, tosylates, and triflates, respectively.

What is the mechanism of converting an alcohol to a sulfonate ester?

The mechanism involves the nucleophilic attack of the alcohol's oxygen on the sulfur atom of the sulfonyl chloride. This forms a tetrahedral intermediate, which then collapses, expelling a chloride ion and forming the sulfonate ester. The reaction proceeds with retention of configuration because the oxygen atom remains in the same spatial position throughout the process. The final product is a stable sulfonate ester, which can be used in subsequent nucleophilic substitution reactions.

What are the common types of sulfonate esters and their corresponding sulfonyl chlorides?

Common types of sulfonate esters include mesylates, tosylates, and triflates. Mesylates are derived from mesyl chloride (CH₃SO₂Cl), tosylates from tosyl chloride (C₇H₇SO₂Cl), and triflates from triflyl chloride (CF₃SO₂Cl). These sulfonate esters are widely used in organic synthesis due to their excellent leaving group properties, which facilitate various nucleophilic substitution reactions.

Why do sulfonate esters retain configuration during their formation from alcohols?

Sulfonate esters retain configuration during their formation from alcohols because the reaction mechanism does not involve a backside attack. The oxygen atom of the alcohol directly attacks the sulfur atom of the sulfonyl chloride, forming a bond without changing the spatial arrangement of the atoms. This retention of configuration is in contrast to reactions involving thionyl chloride or phosphorus tribromide, which proceed with inversion of configuration due to backside attack mechanisms.