Phthalic anhydride

Phthalic anhydride was first reported in 1836 by Auguste Laurent. Early procedures involved liquid-phase mercury-catalyzed oxidation of naphthalene.{{cite journal |last1=Laurent |first1=Aug. |title=Sur l'acide naphtalique et ses combinaisons |journal=Annales de Chimie et de Physique |date=1836 |volume=61 |pages=113–125 |url=https://babel.hathitrust.org/cgi/pt?id=hvd.hx3dwy&view=1up&seq=119 |series=2nd series |trans-title=On naphthalic acid and its compounds |language=French}} The modern industrial variant process instead uses vanadium pentoxide (V₂O₅) as the catalyst in a gas-phase reaction with naphthalene using molecular oxygen. The overall process involves oxidative cleavage of one of the rings and loss of two of the carbon atoms as carbon dioxide.

An alternative process involves oxidation of the two methyl groups of o-xylene, a more atom-economical process. This 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 + {{sfrac|7|1|2}} 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–Wohl naphthalene oxidation reaction) has declined relative to the o-xylene route.

File:V2O5OxNaphth.svg-catalyzed oxidation of naphthalene to phthalic anhydride, with V₂O₅ represented as a molecule versus its true extended structure.{{cite book|doi=10.1002/9780470638859.conrr270|chapter=Gibbs-Wohl Naphthalene Oxidation|title=Comprehensive Organic Name Reactions and Reagents|year=2010|pages=1227–1229 |isbn=9780470638859}}]]

Phthalic anhydride can also be prepared from phthalic acid by simple thermal dehydration above 210°C.{{Ullmann|first1=Peter M.|last1=Lorz|first2=Friedrich K. |last2=Towae|first3= Walter|last3=Enke|first4=Rudolf|last4=Jäckh|first5=Naresh|last5= Bhargava|first6=Wolfgang|last6=Hillesheim|display-authors=3|year=2007|doi=10.1002/14356007.a20_181.pub2|isbn=978-3527306732|title=Phthalic Acid and Derivatives}}

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 million tonnes 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 {{eqm}} C₆H₄(CO₂R)₂ + H₂O

The most important diester is bis(2-ethylhexyl) phthalate ("DEHP"), used in the manufacture of polyvinyl chloride compounds.

File:Quinoline Yellow SS.svg is a popular dye derived from the condensation of phthalic anhydride and 2-methylquinoline.]]

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 anthraquinone dye quinizarin by reaction with para-chlorophenol followed by hydrolysis of the chloride.{{OrgSynth | author = L. A. Bigelow and H. H. Reynolds | title = Quinizarin | collvol = 1 | collvolpages = 476| year = 1941 | prep = CV1P0476}} 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.{{cite journal | author = Baeyer, A. | date = 1871 | title = Ueber eine neue Klasse von Farbstoffen | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 4 | issue = 2 | pages = 555–558 | doi = 10.1002/cber.18710040209 | url = https://zenodo.org/record/1425008 }}{{cite journal | author = Baeyer, A. | date = 1871 | title = Ueber die Phenolfarbstoffe | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 4 | issue = 2 | pages = 658–665 | doi = 10.1002/cber.18710040247 | url = https://zenodo.org/record/1425010 }}{{cite journal | author = Baeyer, A. | date = 1871 | title = Ueber die Phenolfarbstoffe | journal = Polytechnisches Journal | volume = 201 | issue = 89 | pages = 358–362 | url = http://dingler.culture.hu-berlin.de/article/pj201/ar201089 }}

File:Phenolphthalein Synthesis.svgMax Hubacher, {{US patent|2192485}} (1940 to Ex Lax Inc)]]

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.{{Cite journal| vauthors=Neurath AR |title=Microbicide for prevention of sexually transmitted diseases using a pharmaceutical excipient. |journal= AIDS Patient Care STDs |volume=14 |issue= 4 |pages= 215–9 |year= 2000 |pmid= 10806641 |doi= 10.1089/108729100317830}} Phthalic anhydride is a degradation product of CAP.{{Cite journal|vauthors=Mayhew JW, Gideon LT, Ericksen B, Hlavaty JJ, Yeh SM, Chavdarian CG, Strick N, Neurath AR |display-authors=3|title=Development of a gel permeation chromatographic assay to achieve mass balance in cellulose acetate phthalate stability studies. |journal= J Pharm Biomed Anal |volume=49 |issue= 2 |pages= 240–6 |year= 2009 |pmid=19070984 |pmc= 2859192 |doi= 10.1016/j.jpba.2008.10.039}}

Phthalic anhydride is a versatile intermediate in organic chemistry, in part because it is bifunctional and cheaply available.

Hydrolysis by hot water forms ortho-phthalic acid:{{cite book | last = Noller | first = Carl R. | title = Chemistry of Organic Compounds |edition=3rd | publisher = W. B. Saunders | year = 1965 | location = Philadelphia | pages = 602 }}

: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.{{OrgSynth | author = Joseph Kenyon | title = d- and l-Octanol-2| collvol = 1 | collvolpages = 418| year = 1941 | prep = CV1P0418}} A related ring-opening reaction involves peroxides to give the useful peroxy acid:{{OrgSynth | author = George B. Payne | title = Monoperphthalic acid| collvol = 5 | collvolpages = 805| year = 1973 | prep = CV5P0805}}

:C₆H₄(CO)₂O + H₂O₂ → C₆H₄(CO₃H)CO₂H

Phthalimide can be prepared by heating phthalic anhydride with aqueous ammonia giving a 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.{{OrgSynth | title = β-Bromoethylphthalimide | collvol = 1 | collvolpages = 119 | prep = cv1p0119 | year = 1941 | author = P. L. Salzberg and J. V. Supniewski}}

Phthalic anhydride is used to dehydrate short-chain nitro-alcohols to yield nitroalkenes, compounds with a high tendency to polymerize.{{cite journal|author1=Ranganathan, Darshan |author2=Rao, Bhushan |author3=Ranganathan, Subramania |author4=Mehrotra, Ashok |author5=Iyengar, Radha |display-authors=3|name-list-style=amp |title=Nitroethylene: a stable, clean, and reactive agent for organic synthesis|journal=The Journal of Organic Chemistry|year=1980|volume=45|issue=7|pages=1185–1189|doi=10.1021/jo01295a003}}

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's reaction on human health is generally an asthma–rhinitis–conjunctivitis syndrome or a delayed reaction and influenza-like symptoms and with increased immunoglobulin (E and G) levels in the blood.

{{reflist}}

• [http://www.inchem.org/documents/icsc/icsc/eics0315.htm International Chemical Safety Card 0315]
• [https://www.cdc.gov/niosh/npg/npgd0512.html NIOSH Pocket Guide to Chemical Hazards]

{{Authority control}}

{{DEFAULTSORT:Phthalic Anhydride}}

Category:Carboxylic anhydrides

Category:Phthalides

Category:Commodity chemicals

Category:Substances discovered in the 19th century