Phthaloyl Dichloride1

[88-95-9]  · C8H4Cl2O2  · Phthaloyl Dichloride  · (MW 203.02)

(converts carboxylic acids to acid chlorides;2 phthaloyl protecting group for amines;3 useful Friedel-Crafts synthon4)

Physical Data: mp 15-16 °C; bp 281 °C, 131-133 °C/9-10 mmHg; d 1.409 g cm-3.

Solubility: sol CH2Cl2, THF, sulfolane, nitrobenzene.

Form Supplied in: liquid; commercially available; phthalic anhydride is an impurity.

Handling, Storage, and Precautions: store in the absence of moisture; corrosive, handle with gloves in a fume hood.

Conversion of Acids and Esters to Acid Chlorides.

Phthaloyl dichloride has been used for the conversion of acids into acid chlorides,2 and anhydrides into bis-acid chlorides (eq 1).5

It is particularly suited to the preparation of fairly volatile acid chlorides which can be simply distilled out of the reaction mixture, though a greater range of chlorides can be prepared than with lower boiling Benzoyl Chloride. Zinc Chloride has been used as a catalyst. Phthaloyl dichloride has been used in a two-pot sequence for the in situ generation of acetyl chloride from Carbon Dioxide, using catalytic N,N-Dimethylformamide.6 In the presence of Chlorosulfonic Acid, it performs the useful conversion of ethyl esters into acid chlorides (eq 2).7

Protection of Amines.

Amines can be protected with the phthaloyl group using phthaloyl dichloride and 4-Dimethylaminopyridine or Pyridine.3 This method may offer an advantage over more usual procedures, e.g. phthalic anhydride, in hindered cases.

Friedel-Crafts Reactions.

Though not strictly acting as a reagent, phthaloyl dichloride undergoes Friedel-Crafts acylation of hydroquinones to give 1,4-dihydroxyanthraquinones, the ring system of the daunomycin antitumour family (eq 3).4

Miscellaneous.

Aromatic nitro groups have been reported to undergo displacement with fluorine using Potassium Fluoride as the fluoride source (eq 4). Phthaloyl dichloride was found to be an effective trapping agent for K2O, formed by the decomposition of KNO2, by conversion to phthalic anhydride.8


1. Fieser, L. F.; Fieser, M. FF 1967, 1, 1989, 14, 263.
2. Ott, E. OSC 1943, 2, 528.
3. (a) McDonald, I.; Palfreyman, M. G.; Jung, M.; Bey, P. TL 1985, 26, 4091. (b) Schirlin, D.; Gerhart. F.; Hornsperger, J. M.; Hamon, M.; Wagner, J.; Jung, M. J. JMC 1988, 31, 30.
4. Sartori, G.; Casnati, G.; Bigi, F.; Robles, P. TL 1987, 28, 1533.
5. Kyrides, L. P. OSC 1955, 3, 422.
6. Banks, W. R.; Digenis, G. A. TL 1989, 30, 6473.
7. Middleton, W. J. JOC 1979, 44, 2291.
8. Yazawa, N.; Suzuki, H.; Yoshida, Y.; Furusawa, O.; Kimura, Y. CL 1989, 2213.

Peter Hamley

Fisons Pharmaceuticals, Loughborough, UK



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