Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula (CH3CO)2O. Commonly abbreviated Ac2O, it is the simplest isolable anhydride of a carboxylic acid and is widely used as a reagent in organic synthesis. It is a colorless liquid that smells strongly of acetic acid, which is formed by its reaction with moisture in the air.
|Preferred IUPAC name
|Systematic IUPAC name
Acetic acid anhydride
3D model (JSmol)
|Molar mass||102.089 g·mol−1|
|Density||1.082 g cm−3, liquid|
|Melting point||−73.1 °C (−99.6 °F; 200.1 K)|
|Boiling point||139.8 °C (283.6 °F; 412.9 K)|
|2.6 g/100 mL, see text|
|Vapor pressure||4 mmHg (20 °C)|
Refractive index (nD)
|Safety data sheet||ICSC 0209|
|R-phrases (outdated)||R10, R20/22, R34|
|S-phrases (outdated)||(S1/2), S26, S36/37/39, S45|
|Flash point||49 °C (120 °F; 322 K)|
|316 °C (601 °F; 589 K)|
|Lethal dose or concentration (LD, LC):|
LC50 (median concentration)
|1000 ppm (rat, 4 hr)|
|US health exposure limits (NIOSH):|
|TWA 5 ppm (20 mg/m3)|
|C 5 ppm (20 mg/m3)|
IDLH (Immediate danger)
Related acid anhydrides
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Acetic anhydride, like most acid anhydrides, is a flexible molecule with a nonplanar structure. The pi system linkage through the central oxygen offers very weak resonance stabilization compared to the dipole-dipole repulsion between the two carbonyl oxygens. The energy barriers to bond rotation between each of the optimal aplanar conformations are quite low.
Like most acid anhydrides, the carbonyl carbon of acetic anhydride has electrophilic character, as the leaving group is carboxylate. The internal asymmetry may contribute to acetic anhydride's potent electrophilicity as the asymmetric geometry makes one side of a carbonyl carbon more reactive than the other, and in doing so tends to consolidate the electropositivity of a carbonyl carbon to one side (see electron density diagram).
The Tennessee Eastman acetic anhydride process involves the conversion of methyl acetate to methyl iodide and an acetate salt. Carbonylation of the methyl iodide in turn affords acetyl iodide, which reacts with acetate salts or acetic acid to give the product. Rhodium chloride in the presence of lithium iodide is employed as catalysts. Because acetic anhydride is not stable in water, the conversion is conducted under anhydrous conditions.
Due to its low cost, acetic anhydride is usually purchased, not prepared, for use in research laboratories.
Aromatic rings are acetylated by acetic anhydride. Usually acid catalysts are used to accelerate the reaction. Illustrative are the conversions of benzene to acetophenone and ferrocene to acetylferrocene:
Aldehydes react with acetic anhydride in the presence of an acidic catalyst to give geminal diacetates. A former industrial route to vinyl acetate involved the intermediate ethylidene diacetate, the geminal diacetate obtained from acetaldehyde and acetic anhydride:
Acetic anhydride dissolves in water to approximately 2.6% by weight. Aqueous solutions have limited stability because, like most acid anhydrides, acetic anhydride hydrolyses to give carboxylic acids. In this case, acetic acid is formed:
As indicated by its organic chemistry, acetic anhydride is mainly used for acetylations leading to commercially significant materials. Its largest application is for the conversion of cellulose to cellulose acetate, which is a component of photographic film and other coated materials, and is used in the manufacture of cigarette filters. Similarly it is used in the production of aspirin (acetylsalicylic acid), which is prepared by the acetylation of salicylic acid. It is also used as a wood preservative via autoclave impregnation to make a longer-lasting timber.
In starch industry, acetic anhydride is a common acetylation compound, used for the production of modified starches (E1414, E1420, E1422)
Acetic anhydride is an irritant and combustible liquid. Because of its reactivity toward water, alcohol foam or carbon dioxide are preferred for fire suppression. The vapour of acetic anhydride is harmful.
Acetic acid , systematically named ethanoic acid , is a colourless liquid organic compound with the chemical formula CH3COOH (also written as CH3CO2H or C2H4O2). When undiluted, it is sometimes called glacial acetic acid. Vinegar is no less than 4% acetic acid by volume, making acetic acid the main component of vinegar apart from water. Acetic acid has a distinctive sour taste and pungent smell. In addition to household vinegar, it is mainly produced as a precursor to polyvinyl acetate and cellulose acetate. It is classified as a weak acid since it only partially dissociates in solution, but concentrated acetic acid is corrosive and can attack the skin.
Acetic acid is the second simplest carboxylic acid (after formic acid). It consists of a methyl group attached to a carboxyl group. It is an important chemical reagent and industrial chemical, used primarily in the production of cellulose acetate for photographic film, polyvinyl acetate for wood glue, and synthetic fibres and fabrics. In households, diluted acetic acid is often used in descaling agents. In the food industry, acetic acid is controlled by the food additive code E260 as an acidity regulator and as a condiment. In biochemistry, the acetyl group, derived from acetic acid, is fundamental to all forms of life. When bound to coenzyme A, it is central to the metabolism of carbohydrates and fats.
The global demand for acetic acid is about 6.5 million metric tons per year (Mt/a), of which approximately 1.5 Mt/a is met by recycling; the remainder is manufactured from methanol. Vinegar is mostly dilute acetic acid, often produced by fermentation and subsequent oxidation of ethanol.Acetic formic anhydride
Acetic formic anhydride is an organic compound with the chemical formula C3H4O3 and a structural formula of H3C-(C=O)-O-(C=O)H. It can be viewed as the mixed anhydride of acetic acid and formic acid.Acetic oxalic anhydride
Acetic oxalic anhydride is an organic compound with a chemical formula of C6H6O6 and a structural formula of (H3C-(C=O)-O-(C=O)-)2. It can be viewed as a mixed anhydride, formally derived from acetic acid (H3C-(C=O)OH) and oxalic acid ((-(C=O)OH)2), in 2:1 molecular ratio, by the loss of two water molecules.Acetyl iodide
Acetyl iodide is an organoiodine compound with the formula CH3COI. It is a colourless liquid. It is formally derived from acetic acid. Although far rarer in the laboratory than the related acetyl bromide and acetyl chloride, acetyl iodide is produced, transiently at least, on a far larger scale than any other acid halide. Specifically, it is generated by the carbonylation of methyl iodide in the Cativa and Monsanto processes that are the main industrial route to acetic acid. It is also an intermediate in the production of acetic anhydride from methyl acetate.Upon treatment with carboxylic acids, acetyl iodide does not exhibit reactions typical of acyl halides, such as acetyl chloride. Instead, acetyl iodide undergoes iodide/hydroxide exchange with most carboxylic acids:
CH3COI + RCO2H → CH3CO2H + RCOICalcium permanganate
Calcium permanganate is an oxidizing agent and chemical compound with the chemical formula Ca(MnO4)2. It consists of the metal calcium and two permanganate ions. It is noncombustible, but, being a strong oxidizing agent, it will accelerate the burning of combustible material. If the combustible material is finely divided, the resulting mixture may be explosive. Contact with liquid combustible materials may result in spontaneous ignition. Contact with sulfuric acid may cause fires or explosions. Mixtures with acetic acid or acetic anhydride can explode if not kept cold. Explosions can occur when mixtures of calcium permanganate and sulfuric acid come into contact with benzene, carbon disulfide, diethyl ether, ethyl alcohol, petroleum, or other organic matter.
It is prepared from the reaction of potassium permanganate with calcium chloride or from the reaction of aluminium permanganate with calcium oxide. It can be also prepared by reacting manganese dioxide with a solution of calcium hypochlorite and a little bit of calcium hydroxide to increase the pH level. If manganese dioxide is heated with calcium hydroxide with an oxidier such as Ca(NO3)2, Ca(ClO3)2, or Ca(ClO4)2, it will produce calcium manganate or mangamite ('hypomanganate').Cellobiose
Cellobiose is a disaccharide with the formula C12H22O11. Cellobiose, a reducing sugar, consists of two β-glucose molecules linked by a β(1→4) bond. It can be hydrolyzed to glucose enzymatically or with acid. Cellobiose has eight free alcohol (OH) groups, one acetal linkage and one hemiacetal linkage, which give rise to strong inter- and intramolecular hydrogen bonds. It can be obtained by enzymatic or acidic hydrolysis of cellulose and cellulose rich materials such as cotton, jute, or paper. Cellobiose can be used as an indicator carbohydrate for Crohn's disease and malabsorption syndrome.Treatment of cellulose with acetic anhydride and sulfuric acid, gives cellobiose octoacetate, which is no longer a hydrogen bond donor (though it is still a hydrogen bond acceptor) and is soluble in nonpolar organic solvents.Cellulose triacetate
Cellulose triacetate, (triacetate, CTA or TAC) is a chemical compound produced from cellulose and a source of acetate esters, typically acetic anhydride. Triacetate is commonly used for the creation of fibres and film base. It is chemically similar to cellulose acetate. Its distinguishing characteristic is that in triacetate, at least "92 percent of the hydroxyl groups are acetylated." During the manufacture of triacetate, the cellulose is completely acetylated; whereas in normal cellulose acetate or cellulose diacetate, it is only partially acetylated. Triacetate is significantly more heat resistant than cellulose acetate.Clandestine chemistry
Clandestine chemistry is chemistry carried out in secret, and particularly in illegal drug laboratories. Larger labs are usually run by gangs or organized crime intending to produce for distribution on the black market. Smaller labs can be run by individual chemists working clandestinely in order to synthesize smaller amounts of controlled substances or simply out of a hobbyist interest in chemistry, often because of the difficulty in ascertaining the purity of other, illegally synthesized drugs obtained on the black market. The term clandestine lab is generally used in any situation involving the production of illicit compounds, regardless of whether the facilities being used qualify as a true laboratory.Erlenmeyer–Plöchl azlactone and amino-acid synthesis
The Erlenmeyer–Plöchl azlactone and amino acid synthesis, named after Friedrich Gustav Carl Emil Erlenmeyer who partly discovered the reaction, is a series of chemical reactions which transform an N-acyl glycine to various other amino acids via an oxazolone (also known as an azlactone).
Hippuric acid, the benzamide derivative of glycine, cyclizes in the presence of acetic anhydride, condensing to give 2-phenyl-oxazolone. This intermediate also has two acidic protons and reacts with benzaldehyde, acetic anhydride and sodium acetate to a so-called azlactone. This compound on reduction gives access to phenylalanine.Liebermann–Burchard test
The Liebermann–Burchard or acetic anhydride test is used for the detection of cholesterol. The formation of a green or green-blue colour after a few minutes is positive.
Lieberman–Burchard is a reagent used in a colourimetric test to detect cholesterol, which gives a deep green colour. This colour begins as a purplish, pink colour and progresses through to a light green then very dark green colour. The colour is due to the hydroxyl group (-OH) of cholesterol reacting with the reagents and increasing the conjugation of the un-saturation in the adjacent fused ring. Since this test uses acetic anhydride and sulfuric acid as reagents, caution must be exercised so as not to receive severe burns.
Method: Dissolve one or two crystals of cholesterol in dry chloroform in a dry test tube. Add several drops of acetic anhydride and then 2 drops of concentrated H2SO4 and mix carefully.
After the reaction is finished, the concentration of cholesterol can be measured using spectrophotometry.Lumière–Barbier method
The Lumière–Barbier method is a method of acetylating aromatic amines in aqueous solutions. An example of this is the acetylation of aniline.
First aniline is dissolved in water using one equivalent of hydrochloric acid:
Then 1.2 equivalents of acetic anhydride is added followed by 1.2 equivalents of aqueous sodium acetate solution. Aniline attacks acetic anhydride followed by deprotonation of the ammonium ion:
Acetate then acts as a leaving group:
The acetanilide product is insoluble in water and can therefore be filtered off as crystals.Menke nitration
The Menke nitration is the nitration of electron rich aromatic compounds with cupric nitrate and acetic anhydride. The reaction introduces the nitro group predominantly in the ortho position to the activation group. The reaction is named after the Dutch chemist J.B. Menke.Monsanto process
The Monsanto process is an industrial method for the manufacture of acetic acid by catalytic carbonylation of methanol. The Monsanto process has largely been supplanted by the Cativa process, a similar iridium-based process developed by BP Chemicals Ltd which is more economical and environmentally friendly.
This process operates at a pressure of 30–60 atm and a temperature of 150–200 °C and gives a selectivity greater than 99%. It was developed in 1960 by the German chemical company, BASF, and improved by the Monsanto Company in 1966, which introduced a new catalyst system.Organic acid anhydride
An organic acid anhydride is an acid anhydride that is an organic compound. An acid anhydride is a compound that has two acyl groups bonded to the same oxygen atom. A common type of organic acid anhydride is a carboxylic anhydride, where the parent acid is a carboxylic acid, the formula of the anhydride being (RC(O))2O. Symmetrical acid anhydrides of this type are named by replacing the word acid in the name of the parent carboxylic acid by the word anhydride. Thus, (CH3CO)2O is called acetic anhydride. Mixed (or unsymmetrical) acid anhydrides, such as acetic formic anhydride (see below), are known.
One or both acyl groups of an acid anhydride may also be derived from another type of organic acid, such as sulfonic acid or a phosphonic acid. One of the acyl groups of an acid anhydride can be derived from an inorganic acid such as phosphoric acid. The mixed anhydride 1,3-bisphosphoglyceric acid, an intermediate in the formation of ATP via glycolysis, is the mixed anhydride of 3-phosphoglyceric acid and phosphoric acid. Acidic oxides are also classified as acid anhydrides.Organorhodium chemistry
Organorhodium chemistry is the chemistry of organometallic compounds containing a rhodium-carbon chemical bond, and the study of rhodium and rhodium compounds as catalysts in organic reactions.Stable organorhodium compounds and transient organorhodium intermediates are used as catalyst such as in olefin hydroformylation, olefin hydrogenation, olefin isomerization and the Monsanto processPummerer rearrangement
The Pummerer rearrangement is an organic reaction whereby an alkyl sulfoxide rearranges to an α-acyloxy–thioether (monothioacetal-ester) in the presence of acetic anhydride.
The stoichiometry of the reaction is:
RS(O)CHR'2 + Ac2O → RSC(OAc)R'2 + AcOHThebacon
Thebacon (INN; pronounced ), or dihydrocodeinone enol acetate, is a semisynthetic opioid that is similar to hydrocodone and is most commonly synthesised from thebaine. Thebacon is a derivative of acetyldihydrocodeine, where only the 6-7 double bond is saturated. Thebacon is marketed as its hydrochloride salt under the trade name Acedicon, and as its bitartrate under Diacodin and other trade names. The hydrochloride salt has a free base conversion ratio of 0.846. Other salts used in research and other settings include thebacon's phosphate, hydrobromide, citrate, hydroiodide, and sulfate. The US DEA Administrative Controlled Substance Control Number assigned by the Controlled Substances Act 1970 for thebacon and all of its salts is 9737.
Thebacon is an opioid agonist narcotic analgesic of the middle range and a strong antitussive, primarily used in Europe, although it is no longer in common use. Currently, dihydrocodeine and nicocodeine are used as second-line codeine replacements. Thebacon was invented in Germany in 1924, four years after the first synthesis of hydrocodone. The other dihydromorphinone used as an antitussive is hydromorphone (Dilaudid cough syrup); the other narcotic antitussives are either more directly related to codeine or not related at all (open chain methadone relatives and thiambutenes).
Thebacon is indicated for moderate to moderately severe pain and dry painful coughing, like hydrocodone. It has a duration of action in the range of 5 to 9 hours and doses typically start at 5 mg q6h. The drug is most commonly taken orally as an elixir, tablet, or capsule, although rectal and subcutaneous administration has the same advantages with hydrocodone as would taking a tablet or powder or a liquid concentrate buccally or sublingually.
Thebacon is generated by the esterification product of the enol tautomer of hydrocodone (dihydrocodeineone) with acetic anhydride. Although modification of thebaine is the most common way of making thebacon, it is not uncommonly prepared by refluxing hydrocodone with acetic anhydride, generally similar to how diacetylmorphine is produced. It is also a product of the metabolism of hydrocodone by Pseudomonas putida M10, the bacterium used for oil spill remediation. This also produces a morphinone reductase which can turn morphine into hydromorphone in a process which produces other active opioids, such as oxymorphone, oxymorphol, or hydromorphinol as intermediates.
Thebacon's analgesic and antitussive potency is slightly higher than that of its parent compound hydrocodone, which gives it approximately eight times the milligramme strength of codeine. The acetylation at position 3 and the conversion into a dihydromorphinone class semisynthetic (at position 14 on the morphine carbon skeleton) allows for the drug to more rapidly enter the central nervous system in greater quantity where it is de-acetylated into hydromorphone, and also converted by other processes into hydromorphinol, morphine and various other active and inactive substances; it therefore simultaneously takes advantage of two methods of increasing the effectiveness of morphine and its derivatives, those being catalytic hydrogenation (codeine into hydrocodone) and esterification (morphine into diamorphine, nicomorphine &c) in a manner not unlike to that of dihydrodiacetylmorphine.
Like all of its chemical relatives in this class (codeine-based semi-synthetic narcotic antitussives), thebacon exerts its analgesic effect and a large part of its antitussive and antiperistaltic action as a prodrug for stronger and/or longer-lasting opioids, primarily hydromorphone, which is formed in the liver by the cytochrome P450 2D6 (CYP2D6) enzyme pathway as well as acetylmorphone. As a result, the effectiveness of a given dose of thebacon will vary amongst patients, and some food and drugs can affect various parts of the liberation, absorption, distribution, metabolism and elimination profile, and therefore a variable proportion of the potency of thebacon. Thebacon can be said to be the 3-monoacetylmorphine analog of hydrocodone, and/or the acetylmorphone analog of codeine. It is also a close structural relative of 3,14-diacetyloxymorphone.
For both pain and coughing, thebacon can be made more effective along with NSAIDs, muscle relaxants, and/or antihistamines like tripelennamine, hydroxyzine, promethazine, phenyltoloxamine and chlorpheniramine.
Thebacon is a Schedule I controlled substance in the United States, never having been in medical use there.Trifluoroacetic anhydride
Trifluoroacetic anhydride (TFAA) is the acid anhydride of trifluoroacetic acid. It is the perfluorinated derivative of acetic anhydride. Like many acid anhydrides, it may be used to introduce the corresponding trifluoroacetyl group. The corresponding acyl chloride, trifluoroacetyl chloride, is a gas, making it inconvenient to work with. Trifluoroacetic anhydride is the recommended desiccant for trifluoroacetic acid.Wohl degradation
The Wohl degradation in carbohydrate chemistry is a chain contraction method for aldoses. The classic example is the conversion of glucose to arabinose as shown below. The reaction is named after the German chemist Alfred Wohl (1863–1939).
In one modification, d-glucose is converted to the glucose oxime by reaction with hydroxylamine and sodium methoxide. In the second step the pentaacetyl glycononitrile is formed by reaction with acetic anhydride in acetic acid with sodium acetate. In this reaction step the oxime is converted into the nitrile with simultaneous conversion of all the alcohol groups to acetate groups.
In the final step sodium methoxide in methanol is added, leading to removal of all the acetate groups and ejection of the nitrile group and collapse of the second carbon from a tetrahedral structure to an aldehyde.