Acetaldehyde

Acetaldehyde
IUPAC name ethanal
Other names Acetic Aldehyde Ethyl Aldehyde[1]
Identifiers
CAS number	75-07-0 Y
PubChem	177
ChemSpider	172 Y
UNII	GO1N1ZPR3B Y
EC number	200-836-8
KEGG	C00084 Y
ChEBI	CHEBI:15343 Y
ChEMBL	CHEMBL170365 Y
RTECS number	AB1925000
Jmol-3D images	Image 1 Image 2
SMILES O=CC CC=O
InChI InChI=1S/C2H4O/c1-2-3/h2H,1H3 Y Key: IKHGUXGNUITLKF-UHFFFAOYSA-N Y InChI=1/C2H4O/c1-2-3/h2H,1H3 Key: IKHGUXGNUITLKF-UHFFFAOYAB
Properties
Molecular formula	C2H4O
Molar mass	44.05 g mol−1
Appearance	Colourless liquid Pungent, fruity odor
Density	0.788 g cm−3
Melting point	−123.5 °C, 150 K, -190 °F
Boiling point	20.2 °C, 293 K, 68 °F
Solubility in water	soluble in all proportions
Viscosity	~0.215 at 20 °C
Structure
Molecular shape	trigonal planar (sp²) at C1 tetrahedral (sp³) at C2
Dipole moment	2.7 D
Hazards
MSDS	External MSDS
GHS pictograms	[2]
GHS hazard statements	H224, H319, H335, H351[2]
GHS precautionary statements	P210, P261, P281, P305+351+338[2]
EU classification	Very flammable (F+) Harmful (Xn) Carc. Cat. 3
R-phrases	R12 R36/37 R40
S-phrases	(S2) S16 S33 S36/37
NFPA 704	4 2 2
Flash point	234,15 K (-39 °C)
Autoignition temperature	458,15 K (185 °C)
Related compounds
Related aldehydes	Formaldehyde Propionaldehyde
Related compounds	Ethylene oxide
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Acetaldehyde (systematically ethanal) is an organic chemical compound with the formula CH₃CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part of their normal metabolism. It is also produced by oxidation of ethanol and is popularly believed to be a cause of hangovers from alcohol consumption through drinking spirits.^[3] Pathways of exposure include air, water, land or groundwater that can expose the human subject directly if they inhale, drink, or smoke.^[4]

Production

In 2003, global production was about 10⁶ tons/year.^[5] The main production method is the oxidation of ethylene via the Wacker process:

2 CH₂=CH₂ + O₂ → 2 CH₃CHO

Alternatively, hydration of acetylene, catalyzed by mercury salts gives ethenol, which tautomerizes to acetaldehyde. This industrial route was dominant prior to the Wacker process^[6] It is also prepared at smaller levels by both the dehydrogenation and the oxidation of ethanol. Some acetaldehyde forms upon hydrogenation of CO, but this method is not used commercially.^[5]

Reactions

Like many other carbonyl compounds, acetaldehyde tautomerizes to give the enol. The enol of acetaldehyde is vinyl alcohol (IUPAC name: ethenol):

CH₃CH=O $\overrightarrow{\leftarrow}$ CH₂=CHOH

The equilibrium constant is only 6 x 10⁻⁵ at room temperature, so that the amount of the enol in a sample of acetaldehyde is very small.^[7]

Ethanal-ethenol tautomerism

Condensation reactions

Because of its small size and its availability as the anhydrous monomer (unlike formaldehyde), it is a common electrophile in organic synthesis.^[8] With respect to its condensation reactions, acetaldehyde is prochiral. It is mainly used as a source of the "CH₃C⁺H(OH)" synthon in aldol and related condensation reactions.^[9] Grignard reagents and organolithium compounds react with MeCHO to give hydroxyethyl derivatives.^[10] In one of the more spectacular condensation reactions, three equivalents of formaldehyde add to MeCHO to give pentaerythritol, C(CH₂OH)₄.^[11]

In a Strecker reaction, acetaldehyde condenses with cyanide and ammonia to give, after hydrolysis, the amino acid alanine.^[12] Acetaldehyde can condense with amines to yield imines, such as the condensation with cyclohexylamine to give N-ethylidenecyclohexylamine. These imines can be used to direct subsequent reactions like an aldol condensation.^[13]

It is also an important building block for the synthesis of heterocyclic compounds. A remarkable example is its conversion upon treatment with ammonia to 5-ethyl-2-methylpyridine ("aldehyde-collidine”).^[14]

Acetal derivatives

Three molecules of acetaldehyde condense to form “paraldehyde,” a cyclic trimer containing C-O single bonds. The condensation of four molecules of acetaldehyde give the cyclic molecule called metaldehyde.

Acetaldehyde forms a stable acetal upon reaction with ethanol under conditions that favor dehydration. The product, CH₃CH(OCH₂CH₃)₂, is in fact called "acetal,"^[15] although acetal is used more widely to describe other compounds with the formula RCH(OR')₂.

Uses

Traditionally, acetaldehyde was mainly used as a precursor to acetic acid. This application has declined because acetic acid is made more efficiently from methanol by the Monsanto and Cativa processes. In terms of condensation reactions, 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.

Indoor Air Exposure

Although a relatively weak sensory irritant, acetaldehyde is a common contaminant in workplace, indoor, and ambient environments. It is also a potential carcinogen. ^[16]

Biochemistry and health effects

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.^[17] In the brain, alcohol dehydrogenase has a minor role in the oxidation of ethanol to acetaldehyde. Instead, the enzyme catalase primarily oxidizes ethanol to acetaldehyde.^[17] The last steps of alcoholic fermentation in bacteria, plants and yeast involve the conversion of pyruvate into acetaldehyde 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.

Tobacco addiction

Acetaldehyde is a significant constituent of tobacco smoke. It has been demonstrated to have a synergistic effect with nicotine, increasing the onset and tenacity of addiction to cigarette smoking, particularly in adolescents.^[18][19]

Alzheimer's disease

People who have 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 [late-onset Alzheimer's disease] …"^[20]

Alcohol problems

Acetaldehyde derived from the consumption of ethanol binds to proteins to form adducts that are linked to organ disease.^[21]

The drug disulfiram (Antabuse) prevents the oxidation of acetaldehyde to acetic acid, and it has the same unpleasant effect on drinkers. Antabuse is sometimes used as a deterrent for alcoholics who wish to stay sober.

Carcinogen

Acetaldehyde is a probable carcinogen in humans.^[22] In 1988 the International Agency for Research on Cancer stated, "There is sufficient evidence for the carcinogenicity of acetaldehyde (the major metabolite of ethanol) in experimental animals."^[23] 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.^[24] In addition, acetaldehyde is damaging to DNA^[25] and causes abnormal muscle development as it binds to proteins.^[26]

A study of 818 heavy drinkers found that those who are 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.^[27]

Safety

Acetaldehyde is toxic when applied externally for prolonged periods, an irritant, and a probable carcinogen.^[22] It is an air pollutant resulting from combustion, such as automotive exhaust and tobacco smoke. It is also created by thermal degradation of polymers in the plastics processing industry.^[28] Acetaldehyde naturally breaks down in the human body^[29] but has been shown to excrete in urine of rats.^[30]

See also

• Wine fault
• Alcohol dehydrogenase

References

1. ^ SciFinderScholar (accessed Nov 4, 2009). Acetaldehyde (75-07-0) Substance Detail.
2. ^ ^{a b c} Online Sigma Catalogue , accessdate: May 26, 2011.
3. ^ How Hangovers Work, HowStuffWorks
4. ^ CHEMICALS IN THE ENVIRONMENT: ACETALDEHYDE (CAS NO. 75-07-0)
5. ^ ^{a b} Marc Eckert, Gerald Fleischmann, Reinhard Jira, Hermann M. Bolt, Klaus Golka “Acetaldehyde” in Ullmann's Encyclopedia of Industrial Chemistry, 2006, Wiley-VCH, Weinheim. doi:10.1002/14356007.a01_031.pub2.
6. ^ Dmitry A. Ponomarev and Sergey M. Shevchenko (2007). "Hydration of Acetylene: A 125th Anniversary". J. Chem. Ed. 84 (10): 1725. doi:10.1021/ed084p1725. http://jchemed.chem.wisc.edu/HS/Journal/Issues/2007/OctACS/ACSSub/p1725.pdf. 
7. ^ March, J. “Organic Chemistry: Reactions, Mechanisms, and Structures” J. Wiley, New York: 1992. ISBN 0-471-58148-8.
8. ^ Sowin, T. J.; Melcher, L. M. ”Acetaldehyde” in Encyclopedia of Reagents for Organic Synthesis (Ed: L. Paquette) 2004, J. Wiley & Sons, New York. doi:10.1002/047084289X
9. ^ Behrens, C.; Paquette, L. A. (2004), "N-Benzyl-2,3-Azetidinedione", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=V75P0106 ; Coll. Vol. 10: 41 
10. ^ Walter, L. A. (1955), "1-(α-Pyridyl)-2-Propanol", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv3p0757 ; Coll. Vol. 3: 757 
11. ^ Schurink, H. B. J. (1941), "Pentaerythritol", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV1P0425 ; Coll. Vol. 1: 425 
12. ^ Kendall, E. C. McKenzie, B. F. (1941), "dl-Alanine", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV1P0021 ; Coll. Vol. 1: 21 
13. ^ Wittig, G.; Hesse, A. (1988), "Directed Aldol Condensations: β-Phenylcinnamaldehyde", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0901 ; Coll. Vol. 6: 901 
14. ^ Frank, R. L.; Pilgrim, F. J.; Riener, E. F. (1963), "5-Ethyl-2-Methylpyridine", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV4P0451 ; Coll. Vol. 4: 451 
15. ^ Adkins, H.; Nissen, B. H. (1941), "Acetal", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV1P0001 ; Coll. Vol. 1: 1 
16. ^ Spengler, John D.; McCarthy, John F.; Samet, Jonathan M.. Indoor Air Quality Handbook. New York, NY, USA: McGraw-Hill Professional Publishing, 2000. p 761. http://site.ebrary.com/lib/umassa/Doc?id=10180080&ppg=761 Copyright © 2000. McGraw-Hill Professional Publishing. All rights reserved.
17. ^ ^{a b} Hipolito, L.; Sanchez, M. J.; Polache, A.; Granero, L. Brain metabolism of ethanol and alcoholism: An update. Curr. Drug Metab. 2007, 8, 716-727.
18. ^ Study Points to Acetaldehyde-Nicotine Combination in Adolescent Addiction
19. ^ Nicotine's addictive hold increases when combined with other tobacco smoke chemicals, UCI study finds
20. ^ "Mitochondrial ALDH2 Deficiency as an Oxidative Stress". Annals of the New York Academy of Sciences 1011: 36–44. April 2004. doi:10.1196/annals.1293.004. PMID 15126281. http://www3.interscience.wiley.com/journal/118765604/abstract?CRETRY=1&SRETRY=0. Retrieved 2009-08-13. 
21. ^ Nakamura, K.; Iwahashi, K.; Furukawa, A.; Ameno, K.; Kinoshita, H.; Ijiri, I.; Sekine, Y.; Suzuki, K.; Iwata, Y.; Minabe, Y.; Mori, N. Acetaldehyde adducts in the brain of alcoholics. Arch. Toxicol. 2003, 77, 591.
22. ^ ^{a b} Chemical Summary For Acetaldehyde, US Environmental Protection Agency
23. ^ International Agency for Rescarch on Cancer, World Health Organization. (1988). Alcohol drinking. Lyon: World Health Organization, International Agency for Research on Cancer. ISBN 92-832-1244-4. http://monographs.iarc.fr/ENG/Monographs/vol44/volume44.pdf.  p3
24. ^ International Agency for Research on Cancer Monograph Working Group, Special Report: Policy A review of human carcinogens—Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. The Lancet 2009 10, 1033–1034
25. ^ http://www.ist-world.org/ResultPublicationDetails.aspx?ResultPublicationId=2c488c559db74d8cae0c14ae5b65e14e
26. ^ Nicholas S. Aberle, II, Larry Burd, Bonnie H. Zhao and Jun Ren (2004). "Acetaldehyde-induced cardiac contractile dysfunction may be alleviated by vitamin B₁ but not by vitamins B₆ or B₁₂". Alcohol & Alcoholism 39 (5): 450–454. doi:10.1093/alcalc/agh085. PMID 15304379. http://alcalc.oxfordjournals.org/cgi/content/full/39/5/450. 
27. ^ Nils Homann, Felix Stickel, Inke R. König, Arne Jacobs, Klaus Junghanns, Monika Benesova, Detlef Schuppan, Susanne Himsel, Ina Zuber-Jerger, Claus Hellerbrand, Dieter Ludwig, Wolfgang H. Caselmann, Helmut K. Seitz Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers International Journal of Cancer Volume 118, Issue 8, Pages 1998-2002
28. ^ Smoking. (2006). Encyclopædia Britannica. Accessed 27 October 2006.
29. ^ http://www.epa.gov/chemfact/f_acetal.txt
30. ^ Determinations of ethanol, acetaldehyde, and acetate in blood and urine during alcohol oxidation in man

External links

• International Chemical Safety Card 0009
• National Pollutant Inventory - Acetaldehde
• NIOSH Pocket Guide to Chemical Hazards
• Methods for sampling and analysis
• IARC Monograph: "Acetaldehyde"
• Hal Kibbey, Genetic Influences on Alcohol Drinking and Alcoholism, Indiana University Research and Creative Activity, Vol. 17 no. 3.
• United States Food and Drug Administration (FDA) information for acetaldehyde