Itaconic anhydride

As discovered as early as 1836, attempted distillation of citric acid gives the so-called "pyrocitric acid" ("Brenzcitronensäure"), now known as itaconic anhydride.{{citation|surname1=S. Baup|periodical=Justus Liebigs Ann. Chem.|title=Ueber eine neue Pyrogen-Citronensäure, und ueber Benennung der Pyrogen-Säuren überhaupt|volume=19|issue=1|at=pp. 29–38|date=1836|language=German|doi=10.1002/jlac.18360190107

|url=https://zenodo.org/record/1866579}}

File:Itaconsäureanhydrid aus Citronensäure.svg

According to an organic synthesis protocol,{{cite journal|author=R.L. Shriner, S.G. Ford, L.J. Roll|title=Itaconic Anhydride and Itaconic Acid|journal=Organic Syntheses |year =1931|volume=11|page=70|doi=10.15227/orgsyn.011.0070}} itaconic anhydride is obtained from the rapid heating of citric acid monohydrate in a modest yield (37-47 %). The by-product is the thermodynamically more stable citraconic anhydride.{{cite journal|author=R.L. Shriner, S. G. Ford, L. J. Roll |title=Citraconic Anhydride and Citraconic Acid |journal=Organic Syntheses |year=1931 |volume=11 |page=28 |doi=10.15227/orgsyn.011.0028}}

Also when heating anhydrous citric acid to 260 °C in a vacuum, a mixture of itaconic and citraconic anhydride is achieved "in good yield".{{Cite patent|country=US |number =2258947 |title=Production of itaconic and citraconic anhydrides |gdate=1941-10-14 |fdate=1939-9-21 |invent1=J.H. Crowell |assign1=National Aniline & Chemical Co.}}

More productive are processes based on the biotechnologically accessible itaconic acid,{{cite web|title=Final Report Summary – BIO-QED (Quod Erat Demonstrandum: Large scale demonstration for the bio-based bulk chemicals BDO and IA aiming at cost reduction and improved sustainability)|publisher=CORDIS|url=https://cordis.europa.eu/result/rcn/237848_en.html|accessdate=2018-10-01|last=Novamont SpA|date=2018-07-26}} which produces exclusively itaconic anhydride in yields of up to 98% at temperatures of 165-180 °C and pressures of 10-30 mmHg in the presence of catalytic quantities of strong acids, such as concentrated sulphuric acid.{{Cite patent|country=GB |number =854999 |title=A process for the production of itaconic anhydride |gdate=1960-11-23 |fdate=1959-4-6 |assign1=Chas. Pfizer & Co., Inc.}}

File:Itaconsäureanhydrid aus Itaconsäure.svg

In order to avoid overheating and thus higher proportions of citraconic anhydride, the dehydration reaction can also be carried out in higher boiling aromatic solvents such as toluene or xylene in the presence of acidic montmorillonite{{Cite patent|country=US |number =5260456 |title=Process for producing itaconic anhydride |gdate=1993-11-9 |fdate=1992-4-21 |invent1=M. Alas, M. Gubelmann, J.-M. Popa |assign1=Rhone-Poulenc Chimie}} or in cumene in the presence of methanesulfonic acid.{{Cite patent|country=WO |number =9506026 |title=Dehydration of itaconic acid |gdate=1995-3-2 |fdate=1994-8-25 |invent1=A.G. Talma, A.G. Bovenkamp-Bouwman, H.P. Verlaanhooft |assign1=Akzo Nobel N.V.}} In both variants yields of 95-97 % of itaconic anhydride are achieved.

Another process of cyclizing dicarboxylic acids with diethyl carbonate in the presence of a chromium-salen complex with μ-nitrido-bis(triphenylphosphane) chloride as cocatalyst quantitatively provides itaconic anhydride contaminated with citraconic anhydride already at 40 °C in 1 millimolar preparations. However, the reaction is technically uninteresting because of its expensive catalysts.{{citation|surname1=C. Robert, F. de Montigny, C.M. Thomas|periodical=Nature Communications|title=Tandem synthesis of alternating polyesters from renewable resources|volume=2|at=pp. 1–6|date=2011|doi=10.1038/ncomms1596

|pmid=22158441|pmc=3247812|bibcode=2011NatCo...2..586R}}

At temperatures above its melting point, itaconic anhydride converts to citraconic anhydride. Even at significantly lower temperatures, such as in boiling chloroform, isomerization can take place in the presence of tertiary amines.{{citation|surname1=M.C. Galanti, A.V. Galanti|periodical=J. Org. Chem.|title=Kinetic study of the isomerization of itaconic anhydride to citraconic anhydride|volume=47|issue=8|at=pp. 1572–1574|date=1982|doi=10.1021/jo00347a041

}}

File:Citraconsäureanhydrid aus Itaconsäureanhydrid.svg

By treating itaconic anhydride with phosphorus pentachloride (PCl₅), itaconic acid dichloride (itaconyl chloride) is obtained:{{citation|surname1=W. Petri|periodical=Ber. Dtsch. Chem. Ges.|title=Beiträge zur Kenntnis der Itaconsäure, Mesaconsäure und Citraconsäure|volume=14|issue=2|at=pp. 1634–1637|date=1881|language=German|doi=10.1002/cber.18810140213

|url=https://zenodo.org/record/2194673}}

File:Itaconylchlorid Synthese.svg

from which polyamides with reactive vinylidene groups can be formed with diamines.{{citation|surname1=C. Wang, X. Wang, Z. Wie, X. Zeng|periodical=Polym. Mater. Sci. Eng.|title=Synthesis and characterization of poly(p-phenyleneitaconamide)|volume=34|issue=6|at=pp. 9–15|date=2018|doi=10.16865/j.cnki.1000-7555.2018.06.002

}}

Bromination of itaconic anhydride at – 20 °C and subsequent dehydrobromination produces 2-bromomethylmaleic anhydride in 70% yield by shifting the double bond into the five-membered ring.{{citation|surname1=J. Nokami, T. Tamaoka, H. Ogawa, S. Wakabayashi|periodical=Chem. Lett.|title=Facile synthesis of 2-methylene-4-butyrolactones|volume=15|issue=4|at=pp. 541–544|date=1986|doi=10.1246/cl.1986.541

}}

File:Bromierung von Itaconsäureanhydrid.svg

Otto Diels and Kurt Alder already described the addition (Diels-Alder reaction) of the dienophile itaconic anhydride to the diene cyclopentadiene in 1928.{{citation|surname1=O. Diels, K. Alder|periodical=Justus Liebigs Ann. Chem.|title=Synthesen in der hydroaromatischen Reihe|volume=460|issue=1|at=pp. 98–122|date=1928|language=German|doi=10.1002/jlac.19284600106

}} Also furfuryl alcohol, which is accessible from renewable raw materials, reacts as a diene to form the Diels-Alder adduct, in which the reaction of the alcohol group with the cyclic anhydride structure forms a lactone and a carboxylic acid group, i.e. the cyclic half ester of itaconic acid.{{citation|surname1=A.D. Pehere, S. Xu, S.K. Thompson, M.A. Hillmyer, T.R. Hoye|periodical=Org. Lett.|title=Diels-Alder reactions of furans with itaconic anhydride: Overcoming unfavorable thermodynamics|volume=18|issue=11|at=pp. 2584–2587|date=2016|doi=10.1021/acs.orglett.6b00929

|pmid=27214494|pmc=5136459}}

File:Diels-Alder-Reaktionen mit Itaconsäureanhydrid.svg

Itaconic anhydride can react with aromatics such as benzene via Friedel-Crafts acylation. This always happens in such a way that the ring opening occurs at the carbonyl group, which is further away from the methylene group (3-position).{{citation|surname1=K. Kameo, K. Ogawa, K. Takeshita, S. Nakaike, K. Tomisawa, K. Sato|periodical=Chem. Pharm. Bull.|title=Studies on antirheumatic agents: 3-benzoylpropionic acid derivatives|volume=36|issue=6|at=pp. 2050–2060|date=1988|doi=10.1248/cpb.36.2050

|pmid=3240440|doi-access=free}}

File:Friedel-Crafts-Acylierung mit Itaconsäureanhydrid.svg

Nucleophiles such as thiols can easily be added to the methylene group. With other nucleophiles, such as alcohols, ammonia,{{citation|surname1=H. Takeda, T.Tachinami, S. Hosokawa, M. Aburatani, K. Inoguchi, K. Achiwa|periodical=Chem. Pharm. Bull.|title=Efficient Preparation of Optically Active (S)-(-)-3-Methyl-γ-butyrolactone by Catalytic Asymmetric Hydrogenation Using Chiral N-Substituted Pyrrolidinebisphosphine Rhodium Complexes|volume=39|issue=10|at=pp. 2706–2708|date=1991|doi=10.1248/cpb.39.2706

|doi-access=free}} amines and hydroxylamine, itaconic anhydride reacts regioselectively in position 3 to the corresponding esters, amides and hydroxamic acids.

File:Itaconsäureanhydrid Reaktionen mit Nukleophilen.svg

The hydroxamic acid formed with O-benzylhydroxylamine can be cyclized in high yields with dicyclohexylcarbodiimide (DCC) to five-membered isoimides (iminofuranones) or with acetanhydride (Ac₂O) to imides.{{citation|surname1=M. Akiyama, K. Shimizu, S. Aiba, F. Banba|periodical=J. Chem. Soc. Perkin I|title=Synthesis of N-Hydroxymaleimide and N-Hydroxyitaconimide and their related derivatives|at=pp. 2122–2125|date=1980|doi=10.1039/P19800002122

}}

File:Cyclisierungsreaktionen von Itaconhydroxamsäuren.svg

A number of five-, six- and seven-membered heterocycles (such as benzothiazepines) are obtainable from itaconic anhydride in useful yields.{{citation|surname1=A.M. Medway, J. Sperry|periodical=Green Chem.|title=Heterocycle construction using the biomass-derived building block itaconic acid|volume=16|at=pp. 2084–2101|date=2014|issue=4|doi=10.1039/c4gc00014e

}}

File:Benzothiazepinessigsäure aus Itaconsäureanhydrid.svg

As an unsaturated cyclic anhydride, itaconic anhydride undergoes radical polymerization{{citation|surname1=D. Stawski, S. Polowinski|periodical=Polimery|title=Polymerization of itaconic acid|volume=50|issue=2|at=pp. 118–122|date=2005|url=http://en.www.ichp.pl/polimery-polymerization-of-itaconic-acid

}} and via polycondensation with diols or diamines. The two reactions can also be carried out sequentially – first radical polymerization, then polycondensation or vice versa.{{citation|surname1=F.H. Isikgor, C.R. Becer|periodical=Polym. Chem.|title=Lignocellulosic biomass: a sustainable platform for the production of bio-based chemicals and polymers|volume=6|at=pp. 4497–4559|date=2015|issue=25|doi=10.1039/c5py00263j

|arxiv=1602.01684|s2cid=51812213}}{{citation|surname1=T. Okuda, K. Ishimoto, H. Ohara, S. Kobayashi|periodical=Macromolecules|title=Renewable biobased polymeric materials: Facile synthesis of itaconic anhydride-based copolymers with poly(L-lactic acid) grafts|volume=45|issue=10|at=pp. 4166–4174|date=2012|doi=10.1021/ma300387j

|bibcode=2012MaMol..45.4166O}}

Radically produced itaconic anhydride polymers and copolymers can be alkaline hydrolyzed to polyitaconic acids under ring opening or converted into polymeric acid amides or esters subsequent to polymerization.{{citation|surname1=T. Otsu, J.-Z. Yang|periodical=Polymer Int.|title=Radical polymerization of itaconic anhydride and reactions of the resulting polymers with amines and alcohols|volume=25|issue=4|at=pp. 245–251|date=1991|doi=10.1002/pi.4990250408

}}

File:ITA-SMA-Copolymer.svg

The resulting copolymers show properties that suggest a potential use as biomaterials for therapeutic systems and prostheses.{{citation|surname1=S. Shang, S.J. Huang, R.A. Weiss|periodical=Polymer|title=Comb-like ionomers from sustainable resources: Copolymers of itaconic anhydride-co-stearyl methacrylate|volume=52|issue=13|at=pp. 2764–2771|date=2011|doi=10.1016/j.polymer.2011.04.025

}}

Functional polymers exclusively from biogenic monomers involves the ring-opening metathesis polymerisation of an oxanorbornene ester produced from itaconic anhydride and furfuryl alcohol by Diels-Alder lactonisation using a Grubbs II catalyst.{{citation|surname1=Y. Bai, J.H. Clark, T.J. Farmer, I.D.V. Ingram, M. North|periodical=Polymer Chem.|title=Wholly biomass derivable sustainable polymers by ring-opening metathesis polymerization of monomers obtained from furfuryl alcohol and itaconic anhydride|volume=8|issue=20|at=pp. 3074–3081|date=2017|doi=10.1039/C7PY00486A

|url=https://eprints.whiterose.ac.uk/118683/1/ROMP_esters_revised.docx}}

File:ROMP-Reaktion mit ITA-Diels-Alder-Addukt.svg

Category:Carboxylic anhydrides