Phthalic anhydride is the organic compound with the formula C6H4(CO)2O. It is the anhydride of phthalic acid. Phthalic anhydride is a principal commercial form of phthalic acid. It was the first anhydride of a dicarboxylic acid to be used commercially. This white solid is an important industrial chemical, especially for the large-scale production of plasticizers for plastics. In 2000, the worldwide production volume was estimated to be about 3 million tonnes per year.
|Preferred IUPAC name
3D model (JSmol)
CompTox Dashboard (EPA)
|Molar mass||148.1 g/mol|
|Density||1.53 g/cm3, solid; 1.20 g/mL, molten|
|Melting point||131.6 °C (268.9 °F; 404.8 K)|
|Boiling point||295 °C (563 °F; 568 K) sublimates|
|0.62 g/100g (20—25 °C); |
19.0 g/100g (100 °C);
|Vapor pressure||0.0015 mmHg (20°C)|
|R-phrases (outdated)||R22, R37/38, R41, R42/43|
|S-phrases (outdated)||(S2), S23, S24/25, S26, S37/39, S46|
|Flash point||152 °C (306 °F; 425 K)|
|Lethal dose or concentration (LD, LC):|
LD50 (median dose)
|4020 mg/kg (oral, rat)|
1520 mg/kg (oral, mouse)
800 mg/kg (oral, cat)
800-1600 mg/kg (oral, rat)
2210 mg/kg (oral, mouse)
|US health exposure limits (NIOSH):|
|TWA 12 mg/m3 (2 ppm)|
|TWA 6 mg/m3 (1 ppm)|
IDLH (Immediate danger)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Synthesis and productionEdit
Phthalic anhydride was first reported in 1836 by Auguste Laurent. More contemporary[clarification needed] routes include oxidation of naphthalene or ortho-xylene. Vanadium pentoxide (V2O5) is the active oxidant for several key steps of the processes, and is regenerated by molecular oxygen.
Starting from o-xylene, the oxidation reaction is run at about 320–400 °C and has the following stoichiometry:
- C6H4(CH3)2 + 3 O2 → C6H4(CO)2O + 3 H2O
The reaction proceeds with about 70% selectivity. About 10% of maleic anhydride is also produced:
- C6H4(CH3)2 + 7.5 O2 → C4H2O3 +4 H2O + 4 CO2
Phthalic anhydride and maleic anhydride are recovered by distillation by a series of switch condensers.
The naphthalene route (the Gibbs phthalic anhydride process or the Gibbs–Wohg naphthalene oxidation reaction), a process whose use has declined in compared to the o-xylene route, has the following mechanism:
Phthalic anhydride can also be prepared from phthalic acid by simple dehydration.
Phthalate esters plasticizersEdit
The primary use of phthalic anhydride is a precursor to phthalate esters, used as plasticizers in vinyl chloride. Phthalate esters are derived from phthalic anhydride by the alcoholysis reaction. In the 1980s, approximately 6.5×109 kg of these esters were produced annually, and the scale of production was increasing each year, all from phthalic anhydride. The process begins with the reaction of phthalic anhydride with alcohols, giving the monoesters:
- C6H4(CO)2O + ROH → C6H4(CO2H)CO2R
The second esterification is more difficult and requires removal of water:
- C6H4(CO2H)CO2R + ROH ⇌ C6H4(CO2R)2 + H2O
Precursor to dyestuffsEdit
Phthalic anhydride is widely used in industry for the production of certain dyes. A well-known application of this reactivity is the preparation of the anthroquinone dye quinizarin by reaction with para-chlorophenol followed by hydrolysis of the chloride. Phenolphthalein can be synthesized by the condensation of phthalic anhydride with two equivalents of phenol under acidic conditions (hence the name). It was discovered in 1871 by Adolf von Baeyer.
Phthalic anhydride treated with cellulose acetate gives cellulose acetate phthalate (CAP), a common enteric coating excipient that has also been shown to have antiviral activity. Phthalic anhydride is a degradation product of CAP.
Phthalic anhydride is a versatile intermediate in organic chemistry, in part because it is bifunctional and cheaply available.
Hydrolysis, alcoholysis, ammonolysisEdit
- C6H4(CO)2O + H2O → C6H4(CO2H)2
Hydrolysis of anhydrides is not typically a reversible process. Phthalic acid is however easily dehydrated to form phthalic anhydride. Above 180 °C, phthalic anhydride re-forms.
Chiral alcohols form half-esters (see above), and these derivatives are often resolvable because they form diastereomeric salts with chiral amines such as brucine. A related ring-opening reaction involves peroxides to give the useful peroxy acid:
- C6H4(CO)2O + H2O2 → C6H4(CO3H)CO2H
Phthalimide can be prepared by heating phthalic anhydride with aqueous ammonia giving 95–97% yield. Alternatively, it may be prepared by treating the anhydride with ammonium carbonate or urea. It can also be produced by ammoxidation of o-xylene. Potassium phthalimide is commercially available and is the potassium salt of phthalimide. It may be prepared by adding a hot solution of phthalimide to a solution of potassium hydroxide; the desired product precipitates.
Preparation of aliphatic nitroalkenesEdit
The most probable human exposure to phthalic anhydride is through skin contact or inhalation during manufacture or use. Studies show that exposure to phthalic anhydride can cause rhinitis, chronic bronchitis, and asthma. Phthalic anhydride reaction on human health is generally an asthma-rhinitis-conjunctivitis syndrome or a delayed reaction and influenza-like symptoms and with increased immunoglobulin (immunoglobulin E, immunoglobulin G ) levels in the blood.
- "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 835. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4.
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