Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula . It is a colorless liquid or gas, boiling near room temperature. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and is a contributing cause of hangover after alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke. Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.
Although the International Agency for Research on Cancer has listed acetaldehyde as a Group 1 carcinogen, there is insufficient evidence from human studies to prove a cause-and-effect relationship between acetaldehyde exposure and cancer.
History Acetaldehyde was first observed by the Swedish pharmacist/chemist Carl Wilhelm Scheele (1774);Scheele, C. W. (1774) "Om Brunsten eller Magnesia nigra och dess egenskaper" (On brown-stone or black magnesia [i.e., manganese ore] and its properties), Kungliga Svenska vetenskapsakademiens handlingar (Proceedings of the Royal Swedish Academy of Sciences), 35 : 89–116; 177–194. On pages 109–110, Scheele mentions that refluxing ("digesting") ethanol (Alkohol vini) with manganese dioxide (Brunsten) and either hydrochloric acid (Spirtus salis) or sulfuric acid (Spiritus Vitrioli) produces a smell like "Aether nitri" (ethanol treated with nitric acid). Later investigators realized that Scheele had produced acetaldehyde. it was then investigated by the French chemists Antoine François, comte de Fourcroy and Louis Nicolas Vauquelin (1800),Note: Dabit, a pharmacist in Nantes, France, performed a series of experiments and concluded that acetaldehyde was formed when hydrogen in ethanol combined with oxygen in sulfuric acid to form water: Fourcroy and Vauquelin stated that sulfuric acid was not consumed in the production of acetaldehyde: and the German chemists Johann Wolfgang Döbereiner (1821, 1822, 1832)See: Döbereiner named the new "ether" "Sauerstoffäther" (oxygen-ether).
In this paper, Döbereiner made acetaldehyde by exposing ethanol vapor to air in the presence of platinum black. and Justus von Liebig (1835).
In 1835, Liebig named it "aldehyde", and in the middle of the century the name was altered to "acetaldehyde".
Production In 2013, global production was about 438,000 tonnes. Before 1962, ethanol and acetylene were the major sources of acetaldehyde. Since then, ethylene is the dominant feedstock.
The main method of production is the oxidation of ethylene by the Wacker process, which involves oxidation of ethylene using a homogeneous palladium/copper catalyst system:
In the 1970s, the world capacity of the Wacker-Hoechst direct oxidation process exceeded two million tonnes annually.
Smaller quantities can be prepared by the partial oxidation of ethanol in an exothermic reaction. This process typically is conducted over a silver catalyst at about .
This method is one of the oldest routes for the industrial preparation of acetaldehyde.
Other methods Hydration of acetylene Prior to the Wacker process and the availability of cheap ethylene, acetaldehyde was produced by the hydration of acetylene. This reaction is catalyzed by mercury(II) salts:
The mechanism involves the intermediacy of vinyl alcohol, which tautomerizes to acetaldehyde. The reaction is conducted at , and the acetaldehyde formed is separated from water and mercury and cooled to . In the wet oxidation process, iron(III) sulfate is used to reoxidize the mercury back to the mercury(II) salt. The resulting iron(II) sulfate is oxidized in a separate reactor with nitric acid.
The enzyme Acetylene hydratase discovered in the strictly anaerobic bacterium Pelobacter acetylenicus can catalyze an analogous reaction without involving any compounds of mercury. However, it has thus far not been brought to any large-scale or commercial use.
Dehydrogenation of ethanol Traditionally, acetaldehyde was produced by the partial dehydrogenation of ethanol:
In this endothermic process, ethanol vapor is passed at 260–290 °C over a copper-based catalyst. The process was once attractive because of the value of the hydrogen coproduct,Eckert, Marc et al. (2007) "Acetaldehyde" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim but in modern times is not economically viable.
Hydroformylation of methanol The hydroformylation of methanol with catalysts like cobalt, nickel, or iron salts also produces acetaldehyde, although this process is of no industrial importance. Similarly noncompetitive, acetaldehyde arises from synthesis gas with modest selectivity.
Reactions Tautomerization to vinyl alcohol
Like many other carbonyl compounds, acetaldehyde tautomerizes to give an enol (vinyl alcohol; IUPAC name: ethenol):
∆H298,g = +42.7 kJ/mol
The equilibrium constant is 6 at room temperature, thus that the relative amount of the enol form in a sample of acetaldehyde is very small. At room temperature, acetaldehyde () is more stable than vinyl alcohol () by 42.7 kJ/mol:Johnson, R.D. III "CCCBDB NIST Standard Reference Database". nist.gov Overall the keto-enol tautomerization occurs slowly but is catalyzed by acids.
Photo-induced keto-enol tautomerization is viable under atmospheric or stratospheric conditions. This photo-tautomerization is relevant to the Earth's atmosphere, because vinyl alcohol is thought to be a precursor to carboxylic acids in the atmosphere.
Addition and condensation reactions Acetaldehyde is a common electrophile in organic synthesis.Sowin, T. J.; Melcher, L. M. (2004) "Acetaldehyde" in Encyclopedia of Reagents for Organic Synthesis (Ed: L. Paquette), J. Wiley & Sons, New York. In addition reactions acetaldehyde is prochiral. It is used primarily as a source of the "" synthon in aldol reactions and related condensation reactions.. Grignard reagents and organolithium compounds react with MeCHO to give hydroxyethyl derivatives. In one of the more spectacular addition reactions, formaldehyde in the presence of calcium hydroxide adds to MeCHO to give pentaerythritol, and formate.
In a Strecker reaction, acetaldehyde condenses with cyanide and ammonia to give, after hydrolysis, the amino acid alanine. Acetaldehyde can condense with amines to yield imines; for example, with cyclohexylamine to give N-ethylidenecyclohexylamine. These imines can be used to direct subsequent reactions like an aldol condensation.
It is also a building block in the synthesis of heterocyclic compounds. In one example, it converts, upon treatment with ammonia, to 5-ethyl-2-methylpyridine ("aldehyde-collidine").
Polymeric forms
Three molecules of acetaldehyde condense to form "paraldehyde", a cyclic trimer containing C-O single bonds. Similarly condensation of four molecules of acetaldehyde give the cyclic molecule metaldehyde. Paraldehyde can be produced in good yields, using a sulfuric acid catalyst. Metaldehyde is only obtained in a few percent yield and with cooling, often using HBr rather than as the catalyst. At in the presence of acid catalysts, polyacetaldehyde is produced. There are two stereomers of paraldehyde and four of metaldehyde.
The German chemist Valentin Hermann Weidenbusch (1821–1893) synthesized paraldehyde in 1848 by treating acetaldehyde with acid (either sulfuric or nitric acid) and cooling to . He found it quite remarkable that when paraldehyde was heated with a trace of the same acid, the reaction went the other way, recreating acetaldehyde.
Although vinyl alcohol is a tautomeric form of acetaldehyde (), polyvinyl alcohol cannot be produced from acetaldehyde.
Acetal derivatives
Acetaldehyde forms a stable acetal upon reaction with ethanol under conditions that favor dehydration. The product, , is formally named 1,1-diethoxyethane but is commonly referred to as "acetal". This can cause confusion as "acetal" is more commonly used to describe compounds with the functional groups RCH(OR')2 or RR'C(OR'')2 rather than referring to this specific compound — in fact, 1,1-diethoxyethane is also described as the diethyl acetal of acetaldehyde.
Precursor to vinylphosphonic acid Acetaldehyde is a precursor to vinylphosphonic acid, which is used to make adhesives and ion conductive membranes. The synthesis sequence begins with a reaction with phosphorus trichloride:
Biochemistry In the liver, the enzyme alcohol dehydrogenase oxidizes ethanol into acetaldehyde, which is then further oxidized into harmless acetic acid by acetaldehyde dehydrogenase. These two oxidation reactions are coupled with the reduction of to NADH. In the brain, the enzyme catalase is primarily responsible for oxidizing ethanol to acetaldehyde, and alcohol dehydrogenase plays a minor role. The last steps of alcoholic fermentation in bacteria, plants, and yeast involve the conversion of pyruvate into acetaldehyde and carbon dioxide by the enzyme pyruvate decarboxylase, followed by the conversion of acetaldehyde into ethanol. The latter reaction is again catalyzed by an alcohol dehydrogenase, now operating in the opposite direction.
Many East Asian people have an ALDH2 mutation which makes them significantly less efficient at oxidizing acetaldehyde to acetic acid. On consuming alcohol, their bodies tend to accumulate excessive amounts of acetaldehyde, causing the so-called alcohol flush reaction. They develop a characteristic reddening of the skin on the face and body, alongside nausea, headache and general physical discomfort.
Uses Traditionally, acetaldehyde was mainly used as a precursor to acetic acid. This application has declined because acetic acid is produced more efficiently from methanol by the Monsanto and Cativa processes. Acetaldehyde is an important precursor to pyridine derivatives, pentaerythritol, and crotonaldehyde. Urea and acetaldehyde combine to give a useful resin. Acetic anhydride reacts with acetaldehyde to give ethylidene diacetate, a precursor to vinyl acetate, which is used to produce polyvinyl acetate.
The global market for acetaldehyde is declining. Demand has been impacted by changes in the production of plasticizer alcohols, which has shifted because n-butyraldehyde is less often produced from acetaldehyde, instead being generated by hydroformylation of propylene. Likewise, acetic acid, once produced from acetaldehyde, is made predominantly by the lower-cost methanol carbonylation process."Acetaldehyde". ihs.com. The impact on demand has led to increase in prices and thus slowdown in the market.
+Consumption of acetaldehyde (103 t) in 2003(* Included in others -glyoxal/glyoxalic acid, crotonaldehyde, lactic acid, n-butanol, 2-ethylhexanol) Product USA Mexico W. Europe Japan Total Acetic Acid/Acetic anhydride - 11 89 47 147 Acetate esters 35 8 54 224 321 Pentaerythritol 26 – 43 11 80 Pyridine and pyridine bases 73 – 10 * 83 Peracetic acid 23 – – * 23 1,3-Butylene glycol 14 – – * 14 Others 5 3 10 80 98 Total 176 22 206 362 766