Acetyl Chloride
Properties
| State | Liquid (colorless, fuming in moist air, with sharp pungent odor) |
| Color | Colorless |
| Solubility | Reacts with water (hydrolysis to acetic acid and HCl); miscible with ether, acetone, benzene |
| Melting Point | -112°C |
| Boiling Point | 52°C |
About Acetyl Chloride
Acetyl chloride is the most reactive of the common acetyl-delivery reagents — about a thousand times more reactive than acetic acid for nucleophilic acyl substitution and an order of magnitude faster than acetic anhydride. The reactivity is straightforward to explain: chloride is a vastly better leaving group than hydroxide, and the carbonyl carbon in CH3COCl carries enough partial-positive charge that even weak nucleophiles attack readily. That speed is the selling point and also the headache. Acetyl chloride hydrolyzes the moment it touches water, fumes visibly in humid air, and reacts violently with alcohols and amines. The fumes are HCl, which is why bottles are kept tightly sealed and reactions run under nitrogen with anhydrous solvent. The trade-off versus acetic anhydride is real: anhydride is easier to handle and cleaner to work up, but acetyl chloride will acetylate hindered substrates that anhydride struggles with, and it's the reagent of choice when you need to push through a sluggish acetylation. It's also the standard acyl source for Friedel-Crafts acylation with AlCl3 — the Lewis acid abstracts chloride to generate the acylium cation [CH3CO]+, which then attacks aromatic rings. Industrially, it's made by chlorinating acetic acid with thionyl chloride, PCl3, or phosgene, all of which give acetyl chloride and a removable chlorinated byproduct.
Where you'll encounter it
If you've done a Friedel-Crafts acylation in undergraduate or graduate organic chemistry, acetyl chloride is most likely the reagent you used — it's the standard way to install an acetyl group on a benzene ring, with AlCl3 as the Lewis acid catalyst. In a research lab, it's the fallback when acetic anhydride doesn't get the job done — sterically hindered alcohols and weakly nucleophilic anilines often need the extra reactivity. The downside is that you now have to deal with HCl as a stoichiometric byproduct, which means scavenging it with pyridine, triethylamine, or DMAP, and that workup gets longer. The tradeoff is usually worth it when the alternative is a stalled reaction.
Common Uses
- Friedel-Crafts acylation of aromatic rings with AlCl3
- Acetylation of hindered alcohols and weakly nucleophilic amines
- Preparation of mixed anhydrides for selective acyl transfer
- Pharmaceutical and fine-chemical synthesis where speed matters
- Acetyl protection of -OH and -NH2 groups in synthesis
Safety Information
Flammable (flash point 4 °C) and corrosive — both the liquid and its vapor cause severe burns. Reacts violently with water, releasing HCl gas; storage requires a tightly sealed bottle in a dry cabinet. Vapor is lachrymatory at sub-ppm concentrations. Use only in a fume hood with thick gloves and full eye protection; have a sodium bicarbonate solution within reach for spills. TLV is 5 ppm TWA; in practice the smell shows up well below that.
This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals.