Acetaldehyde (IUPAC systematic nameethanal) is anorganic chemical compound with theformulaCH3CH=O, sometimes abbreviated asMeCH=O. It is a colorless liquid or gas, boiling near room temperature. It is one of the most importantaldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit,[11] and is produced by plants. It is also produced by the partial oxidation ofethanol by the liver enzymealcohol dehydrogenase and is a contributing cause ofhangover afteralcohol consumption.[12] Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke.[13] Consumption ofdisulfiram inhibitsacetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.
In 2013, global production was about 438 thousand tons.[23] Before 1962,ethanol andacetylene were the major sources of acetaldehyde. Since then, ethylene is the dominantfeedstock.[24]
The main method of production is the oxidation ofethene by theWacker process, which involves oxidation of ethene using ahomogeneous palladium/copper catalyst system:
2 CH2=CH2 + O2 → 2 CH3CH=O
In the 1970s, the world capacity of the Wacker-Hoechst direct oxidation process exceeded 2 million tonnes annually.
Smaller quantities can be prepared by the partialoxidation of ethanol in an exothermic reaction. This process typically is conducted over a silver catalyst at about 500–650 °C (932–1,202 °F).[24]
2 CH3CH2OH + O2 → 2 CH3CH=O + 2 H2O
This method is one of the oldest routes for the industrial preparation of acetaldehyde.
The mechanism involves the intermediacy ofvinyl alcohol, whichtautomerizes to acetaldehyde. The reaction is conducted at 90–95 °C (194–203 °F), and the acetaldehyde formed is separated from water and mercury and cooled to 25–30 °C (77–86 °F). In thewet oxidation process,iron(III) sulfate is used to reoxidize the mercury back to the mercury(II) salt. The resultingiron(II) sulfate is oxidized in a separate reactor withnitric acid.[24]
The enzymeAcetylene hydratase discovered in the strictly anaerobic bacteriumPelobacter acetylenicus can catalyze an analogous reaction without involving any compounds of mercury.[26] However, it has thus far not been brought to any large-scale or commercial use.
Traditionally, acetaldehyde was produced by the partialdehydrogenation of ethanol:
CH3CH2OH → CH3CH=O + H2
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,[24] but in modern times is not economically viable.
Thehydroformylation ofmethanol with catalysts like cobalt, nickel, or iron salts also produces acetaldehyde, although this process is of no industrial importance. Similarly noncompetitive, acetaldehyde arises fromsynthesis gas with modest selectivity.[24]
Theequilibrium constant is 6×10−7 at room temperature, thus that the relative amount of the enol form in a sample of acetaldehyde is very small.[27] At room temperature, acetaldehyde (CH3CH=O) is more stable thanvinyl alcohol (CH2=CHOH) by 42.7 kJ/mol:[28] Overall the keto-enol tautomerization occurs slowly but is catalyzed by acids.
Photo-induced keto-enol tautomerization is viable underatmospheric or stratospheric conditions. This photo-tautomerization is relevant to the Earth's atmosphere, because vinyl alcohol is thought to be a precursor tocarboxylic acids in the atmosphere.[29][30]
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 moleculemetaldehyde. 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 thanH2SO4 as the catalyst. At −40 °C (−40 °F) in the presence of acid catalysts, polyacetaldehyde is produced.[24] There are twostereomers 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 0 °C (32 °F). He found it quite remarkable that when paraldehyde washeated with a trace of the same acid, the reaction went the other way, recreating acetaldehyde.[38]
Acetaldehyde forms a stableacetal upon reaction withethanol under conditions that favor dehydration. The product,CH3CH(OCH2CH3)2, is formally named1,1-diethoxyethane but is commonly referred to as "acetal".[39] This can cause confusion as "acetal" is more commonly used to describe compounds with thefunctional 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.
In theliver, theenzymealcohol dehydrogenase oxidizesethanol into acetaldehyde, which is then further oxidized into harmlessacetic acid byacetaldehyde dehydrogenase. These two oxidation reactions are coupled with the reduction ofNAD+ toNADH.[41] In the brain, the enzymecatalase is primarily responsible for oxidizing ethanol to acetaldehyde, andalcohol dehydrogenase plays a minor role.[41] The last steps of alcoholicfermentation in bacteria, plants, andyeast involve the conversion ofpyruvate into acetaldehyde andcarbon dioxide by the enzymepyruvate 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.
ManyEast Asian people have anALDH2 mutation which makes them significantly less efficient at oxidizing acetaldehyde. On consuming alcohol, their bodies tend to accumulate excessive amounts of acetaldehyde, causing the so-calledalcohol flush reaction.[42] They develop a characteristic flush on the face and body, along with "nausea, headache and general physical discomfort".[43] Ingestion of the drugdisulfiram, which inhibits ALDH2, leads to a similar reaction(see:§ Aggravating factors below).[44]
The global market for acetaldehyde is declining. Demand has been impacted by changes in the production of plasticizer alcohols, which has shifted becausen-butyraldehyde is less often produced from acetaldehyde, instead being generated by hydroformylation ofpropylene. Likewise,acetic acid, once produced from acetaldehyde, is made predominantly by the lower-cost methanol carbonylation process.[45] The impact on demand has led to increase in prices and thus slowdown in the market.
Production of Acetaldehyde
Consumption of acetaldehyde (103 t) in 2003[24] (* 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
China is the largest consumer of acetaldehyde in the world, accounting for almost half of global consumption in 2012. Major use has been the production of acetic acid. Other uses such aspyridines and pentaerythritol are expected to grow faster than acetic acid, but the volumes are not large enough to offset the decline in acetic acid. As a consequence, overall acetaldehyde consumption inChina may grow slightly at 1.6% per year through 2018. Western Europe is the second-largest consumer of acetaldehyde worldwide, accounting for 20% of world consumption in 2012. As with China, the Western European acetaldehyde market is expected to increase only very slightly at 1% per year during 2012–2018. However,Japan could emerge as a potential consumer for acetaldehyde in the next five years due to newfound use in commercial production ofbutadiene. The supply of butadiene has been volatile in Japan and the rest of Asia. This should provide the much needed boost to the flat market, as of 2013.[46]
Thethreshold limit value is 25ppm (STEL/ceiling value) and the MAK (Maximum Workplace Concentration) is 50 ppm. At 50 ppm acetaldehyde, no irritation or local tissue damage in thenasalmucosa is observed. When taken up by the organism, acetaldehyde is metabolized rapidly in the liver to acetic acid. Only a small proportion is exhaled unchanged. Afterintravenous injection, the half-life in the blood is approximately 90 seconds.[24]
Acetaldehyde is an irritant of the skin, eyes, mucous membranes, throat, and respiratory tract. This occurs at concentrations as low as 1000 ppm. Symptoms of exposure to this compound includenausea,vomiting, andheadache. These symptoms may not happen immediately. Theperception threshold for acetaldehyde in air is in the range between 0.07 and 0.25 ppm.[24] At such concentrations, thefruityodor of acetaldehyde is apparent.Conjunctival irritations have been observed after a 15-minute exposure to concentrations of 25 and 50 ppm, but transient conjunctivitis and irritation of therespiratory tract have been reported after exposure to 200 ppm acetaldehyde for 15 minutes.
Acetaldehyde induces DNA interstrand crosslinks, a form of DNA damage. These can be repaired by either of two replication-coupled DNA repair pathways.[54] The first is referred to as the FA pathway, because it employs gene products defective inFanconi's anemia patients. This repair pathway results in increased mutation frequency and altered mutational spectrum.[54] The second repair pathway requires replication fork convergence, breakage of the acetaldehyde crosslink, translesion synthesis by a Y-family DNA polymerase and homologous recombination.[54]
People with a genetic deficiency for the enzyme responsible for the conversion of acetaldehyde intoacetic acid may have a greater risk ofAlzheimer's disease. "These results indicate that theALDH2 deficiency is a risk factor for LOAD [late-onset Alzheimer's disease] ..."[55]
A study of 818 heavy drinkers found that those exposed to more acetaldehyde than normal through a genetic variant of the gene encoding forADH1C, ADH1C*1, are at greater risk of developing cancers of theupper gastrointestinal tract and liver.[56]
The drugdisulfiram (Antabuse) inhibits acetaldehyde dehydrogenase, an enzyme that oxidizes the compound into acetic acid. Metabolism of ethanol forms acetaldehyde before acetaldehyde dehydrogenase forms acetic acid, but with the enzyme inhibited, acetaldehyde accumulates. If one consumes ethanol while taking disulfiram, the hangover effect of ethanol is felt more rapidly and intensely (disulfiram-alcohol reaction). As such, disulfiram is sometimes used as a deterrent for alcoholics wishing to stay sober.[44]
Acetaldehyde is a potential contaminant in workplace, indoors, and ambient environments. Moreover, the majority of humans spend more than 90% of their time in indoor environments, increasing any exposure and the risk to human health.[57]
In a study inFrance, the mean indoor concentration of acetaldehydes measured in 16 homes was approximately seven times higher than the outside acetaldehyde concentration. Theliving room had a mean of 18.1±17.5 μg m−3 and thebedroom was 18.2±16.9 μg m−3, whereas the outdoor air had a mean concentration of 2.3±2.6 μg m−3.[citation needed]
It has been concluded thatvolatile organic compounds (VOC) such as benzene, formaldehyde, acetaldehyde, toluene, andxylenes have to be considered prioritypollutants with respect to their health effects. It has been pointed that in renovated or completely new buildings, the VOCs concentration levels are often several orders of magnitude higher. The main sources of acetaldehydes in homes include building materials, laminate, PVC flooring, varnished wood flooring, and varnished cork/pine flooring (found in the varnish, not the wood). It is also found in plastics, oil-based and water-based paints, in composite wood ceilings, particle-board, plywood, treated pine wood, and laminated chipboard furniture.[58]
The use of acetaldehyde is widespread in different industries, and it may be released into waste water or the air during production, use, transportation and storage. Sources of acetaldehyde include fuel combustion emissions from stationary internal combustion engines and power plants that burn fossil fuels, wood, or trash, oil and gas extraction, refineries, cement kilns, lumber and wood mills and paper mills.[59] Acetaldehyde is also present in automobile anddiesel exhaust.[60] As a result, acetaldehyde is "one of the most frequently found air toxics with cancer risk greater than one in a million".[15]
Acetaldehyde has been found incannabis smoke. This finding emerged through the use of new chemical techniques that demonstrated the acetaldehyde present was causing DNA damage in laboratory settings.[65]
Manymicrobes produce acetaldehyde from ethanol, but they have a lower capacity to eliminate the acetaldehyde, which can lead to the accumulation of acetaldehyde in saliva, stomach acid, and intestinal contents.Fermented food and many alcoholic beverages can also contain significant amounts of acetaldehyde. Acetaldehyde, derived from mucosal or microbial oxidation of ethanol, tobacco smoke, and diet, appears to act as a cumulative carcinogen in the upper digestive tract of humans.[66] According to European Commission's Scientific Committee on Consumer Safety's (SCCS) "Opinion on Acetaldehyde" (2012) thecosmetic products special risk limit is 5 mg/L and acetaldehyde should not be used inmouth-washing products.[67]
Although the levels produced by this process are minute acetaldehyde has an exceedingly low taste/odor threshold of around 20–40 ppb and can cause an off-taste in bottled water.[69] The level at which an average consumer could detect acetaldehyde is still considerably lower than any toxicity.[70]
Candida albicans in patients with potentially carcinogenic oral diseases has been shown to produce acetaldehyde in quantities sufficient to cause problems.[71]
^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. Onpages 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.
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:Dabit (1800)."Extrait du mémoire du cit. Dabit sur l'éther" [Extract of the memoir by citizen Dabit on ether].Annales de Chimie.34:289–305.
Fourcroy and Vauquelin stated that sulfuric acid was not consumed in the production of acetaldehyde:Fourcroy; Vauquelin (1800)."Sur l'éther préparé à la manière du cit. Dabit" [On the ether prepared in the way of citizen Dabit].Annales de Chimie.34:318–332.
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Döbereiner, J.W. (1832)."Bildung des Sauerstoff-Aethers durch atmosphärische Oxidation des Alkohols" [Formation of oxy-ether by atmospheric oxidation of alcohol].Journal für Chemie und Physik.64:466–8. In this paper, Döbereiner made acetaldehyde by exposing ethanol vapor to air in the presence of platinum black.
^Brock, William H. (1997).Justus von Liebig: The Chemical Gatekeeper. Cambridge University Press. pp. pp. 83–84.ISBN0-521-52473-3.
^Liebig, J. (1835)."Sur les produits de l'oxidation de l'alcool" [On the products of the oxidation of alcohol].Annales de Chimie et de Physique.59: 289–327 See p. 290.Je le décrirai dans ce mémoire sous le nomd'aldehyde; ce nom est formé dealcool dehydrogenatus. [I will describe it in this memoir by the name ofaldehyde; this name is formed fromalcohol dehydrogenatus.]
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