Acetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO, sometimes abbreviated by chemists as MeCHO. 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.
The International Agency for Research on Cancer has listed acetaldehyde as a Group 1 carcinogen. Acetaldehyde is "one of the most frequently found air toxins with cancer risk greater than one in a million".
History
Acetaldehyde was first observed by the Swedish pharmacist/chemist Carl Wilhelm Scheele ; it was then investigated by the French chemists Antoine François, comte de Fourcroy and Louis Nicolas Vauquelin, and the German chemists Johann Wolfgang Döbereiner and Justus von Liebig. In 1835, Liebig named it "aldehyde"; the name was later altered to "acetaldehyde".Production
In 2003, global production was about 1 million 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 system:
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 partial oxidation of ethanol in an exothermic reaction. This process typically is conducted over a silver catalyst at about 500–650 °C.
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 salts:The mechanism involves the intermediacy of vinyl alcohol, which tautomerizes to acetaldehyde. The reaction is conducted at 90–95 °C, and the acetaldehyde formed is separated from water and mercury and cooled to 25–30 °C. In the wet oxidation process, iron sulfate is used to reoxidize the mercury back to the mercury salt. The resulting iron sulfate is oxidized in a separate reactor with nitric acid.
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, 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 of acetaldehyde to vinyl alcohol
Like many other carbonyl compounds, acetaldehyde tautomerizes to give an enol :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: 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.
Condensation reactions
Acetaldehyde is a common electrophile in organic synthesis. In condensation reactions, acetaldehyde is prochiral. It is used primarily as a source of the "CH3C+H" synthon in aldol and related condensation reactions. Grignard reagents and organolithium compounds react with MeCHO to give hydroxyethyl derivatives. In one of the more spectacular condensation reactions, three equivalents of formaldehyde add to MeCHO to give pentaerythritol, C4.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.
Acetal derivatives
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 H2SO4 as the catalyst. At -40 °C in the presence of acid catalysts, polyacetaldehyde is produced., R1 = CH3, R2 = CH3CH2
Acetaldehyde forms a stable acetal upon reaction with ethanol under conditions that favor dehydration. The product, CH3CH2, 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 RCH2 or RR'C2 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 NAD+ 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.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. The impact on demand has led to increase in prices and thus slowdown in the market.
Consumption of acetaldehyde in 2003
| 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 as pyridines 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 in China 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 next five years due to newfound use in commercial production of butadiene. 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.
Safety
Exposure limits
The threshold limit value is 25ppm and the MAK is 50 ppm. At 50 ppm acetaldehyde, no irritation or local tissue damage in the nasal mucosa 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. After intravenous injection, the half-life in the blood is approximately 90 seconds.Dangers
Toxicity
No serious cases of acute intoxication have been recorded. Acetaldehyde naturally breaks down in the human body but has been shown to excrete in urine of rats.Irritation
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 include nausea, vomiting, and headache. These symptoms may not happen immediately. The perception threshold for acetaldehyde in air is in the range between 0.07 and 0.25 ppm. At such concentrations, the fruity odor 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 the respiratory tract have been reported after exposure to 200 ppm acetaldehyde for 15 minutes.Carcinogenicity
Acetaldehyde is carcinogenic in humans. In 1988 the International Agency for Research on Cancer stated, "There is sufficient evidence for the carcinogenicity of acetaldehyde in experimental animals." In October 2009 the International Agency for Research on Cancer updated the classification of acetaldehyde stating that acetaldehyde included in and generated endogenously from alcoholic beverages is a Group I human carcinogen. In addition, acetaldehyde is damaging to DNA and causes abnormal muscle development as it binds to proteins.Aggravating factors
Alzheimer's disease
People with a genetic deficiency for the enzyme responsible for the conversion of acetaldehyde into acetic acid may have a greater risk of Alzheimer's disease. "These results indicate that the ALDH2 deficiency is a risk factor for LOAD ..."Genetic conditions
A study of 818 heavy drinkers found that those exposed to more acetaldehyde than normal through a defect in the gene for acetaldehyde dehydrogenase are at greater risk of developing cancers of the upper gastrointestinal tract and liver.Disulfiram
The drug disulfiram prevents the oxidation of acetaldehyde to acetic acid. Antabuse is sometimes used as a deterrent for alcoholics wishing to stay sober.Indoor air
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.In a study in France, the mean indoor concentration of acetaldehydes measured in 16 homes was approximately seven times higher than the outside acetaldehyde concentration. The living room had a mean of 18.1±17.5 μg m−3 and the bedroom was 18.2±16.9 μg m−3, whereas the outdoor air had a mean concentration of 2.3±2.6 μg m−3.
It has been concluded that volatile organic compounds such as benzene, formaldehyde, acetaldehyde, toluene, and xylenes have to be considered priority pollutants 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, linoleum, wooden varnished, and cork/pine flooring. It is also found in plastic water-based and matt emulsion paints, in wood ceilings, and wooden, particle-board, plywood, pine wood, and chipboard furniture.