The Chemistry of Acid Chlorides, ROCl

Acid Chlorides:

Highly Reactive Carboxylic Acid Derivatives such as Acid Chlorides can be easily formed:

Easy preparation of acid halides from Carboxylic Acids

Easy preparation of acid halides from Carboxylic Acids

Acid Chlorides are:

  • Highly reactive functional groups.
  • Mainly involved in nucleophilic substitution reactions.
  • Have identical reactions to acid bromides and acid anhydrides (so I will only focus on the Chlorides).
Flash animation showing the Step-by-step mechanism of the formation of an Acid Chloride from Thionyl Chloride and a Carboxylic Acid. Click to launch.
Flash animation showing the Step-by-step mechanism of the formation of an Acid Chloride from Thionyl Chloride and a Carboxylic Acid. Click to launch.

Acid Chlorides undergo a fair number of useful reactions. Below is a table illustrating them:

Paths to common, useful products of Acid Chlorides

Paths to common, useful products of Acid Chlorides

The mechanism for all of these substitution reactions begins with the addition of Nu- or :NuH to the δ+ carbon atom of the carbonyl. This then creates an tetrahedral intermediate which then collapses to eject the chlorine (Cl-). The only difference with :NuH is an additional step where a base (such as pyridine) removes the H+ from the nucleophile.

NuH on Acid Chloride

Nucleophilic Substitution using Nu- and :NuH on Acid Chloride

Acid Chlorides can be converted into Ketones using organocopper reagents such as Me2CuLi and Ph2CuLi. This can be extremely useful in increasing chain length, amongst other things. The reason we used organocopper reagents instead of Grignard reagents (which we already know work) is down to how far the reaction goes. Grignard reagents are capable of converting Ketones into tertiary alcohols, and so tend to follow this route to completion.

The reactions involving Hydride ions are all run using weaker sources of H- than LiAlH4 (which would normally be the obvious choice). This is because the LiAlH4 will continue the conversion from an Aldehyde to a primary alcohol.

Addition of Aromatic Rings (Friedel Crafts Acylation):

Aromatic rings have no direct route for attack. They are poor nucleophiles (due to their stability) and as such require the Acid Chloride to be activated (made into a better electrophile) so they can be pulled in.

This activation can be achieved by using a Lewis acid such as AlCl3 or FeBr3. This reaction type is know as a Friedel Crafts Acylation. The animation below shows the mechanism and reaction scheme for this activation, and joining.

Friedel Crafts Acylation Mechanism - Addition of an Aromatic Ring to form Ketone. Click to launch.

Friedel Crafts Acylation Mechanism - Addition of an Aromatic Ring to form Ketone. Click to launch animation.

If you’re wondering why the product does not reach further, simply consider the properties of the carbonyl group. The carbonyl group has electron withdrawing properties and as such reduces the available of electrons in the aromatic ring…requiring stonger conditions to instigate a second acylation reaction.

7 thoughts on “The Chemistry of Acid Chlorides, ROCl

  1. Pingback: Bookmarks about Chemistry

  2. stepnrazor

    one of the good mechanisms for acid chloride formation using thionyl chloride that i have seen on the inet.

  3. Adeeb

    Pretty nice post. I just came across your site and wanted to say
    that I’ve really enjoyed browsing your blog posts. Any way
    I’ll be subscribing to your feed and I hope you write again soon!

  4. Shelvasha

    By far the most helpful breakdown of acyl chloride reactions on the net. Thank you so much!

Comments are closed.