Acetylation

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Salicylic acid is acetylated to form aspirin Aspirin synthesis.png
Salicylic acid is acetylated to form aspirin

In chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed acetate esters or simply acetates . Deacetylation is the opposite reaction, the removal of an acetyl group from a chemical compound.

Contents

Acetylation/deacetylation in biology

Deacylations "play crucial roles in gene transcription and most likely in all eukaryotic biological processes that involve chromatin". [1]

Acetylation is one type of post-translational modification of proteins. The acetylation of the ε-amino group of lysine, which is common, converts a charged side chain to a neutral one. [2] Acetylation/deacetylation of histones also plays a role in gene expression and cancer. [3] These modifications are effected by enzymes called histone acetyltransferases (HATs) and histone deacetylases (HDACs). [4]

Two general mechanisms are known for deacetylation. One mechanism involves zinc binding to the acetyl oxygen. Another family of deacetylases require NAD+, which transfers an ribosyl group to the acetyl oxygen. [1]

Organic synthesis

Acetate esters [5] and acetamides [6] are generally prepared by acetylations. Acetylations are often used in making C-acetyl bonds in Friedel-Crafts reactions. [7] [8] Carbanions and their equivalents are susceptible to acetylations. [9]

Acetylation reagents

Many acetylations are achieved using these three reagents:

H2C=C=O + CH3CO2H → (CH3CO)2O

Acetylation of cellulose

Cellulose is a polyol and thus susceptible to acetylation, which is achieved using acetic anhydride. Acetylation disrupts hydrogen bonding, which otherwise dominates the properties of cellulose. Consequently, the cellulose esters are soluble in organic solvents and can be cast into fibers and films. [11]

Transacetylation

Transacetylation uses vinyl acetate as an acetyl donor and lipase as a catalyst. This methodology allows the preparation of enantio-enriched alcohols and acetates. [12]

See also

Related Research Articles

<span class="mw-page-title-main">Ketene</span> Organic compound of the form >C=C=O

In organic chemistry, a ketene is an organic compound of the form RR'C=C=O, where R and R' are two arbitrary monovalent chemical groups. The name may also refer to the specific compound ethenone H2C=C=O, the simplest ketene.

<span class="mw-page-title-main">Acetyl group</span> Chemical group, –C(=O)CH₃

In organic chemistry, acetyl is a functional group with the chemical formula −COCH3 and the structure −C(=O)−CH3. It is sometimes represented by the symbol Ac. In IUPAC nomenclature, acetyl is called ethanoyl.

<span class="mw-page-title-main">Acetate</span> Salt compound formed from acetic acid and a base

An acetate is a salt formed by the combination of acetic acid with a base. "Acetate" also describes the conjugate base or ion typically found in aqueous solution and written with the chemical formula C
2
H
3
O
2
. The neutral molecules formed by the combination of the acetate ion and a positive ion are also commonly called "acetates". The simplest of these is hydrogen acetate with corresponding salts, esters, and the polyatomic anion CH
3
CO
2
, or CH
3
COO
.

<span class="mw-page-title-main">Fischer–Speier esterification</span>

Fischer esterification or Fischer–Speier esterification is a special type of esterification by refluxing a carboxylic acid and an alcohol in the presence of an acid catalyst. The reaction was first described by Emil Fischer and Arthur Speier in 1895. Most carboxylic acids are suitable for the reaction, but the alcohol should generally be primary or secondary. Tertiary alcohols are prone to elimination. Contrary to common misconception found in organic chemistry textbooks, phenols can also be esterified to give good to near quantitative yield of products. Commonly used catalysts for a Fischer esterification include sulfuric acid, p-toluenesulfonic acid, and Lewis acids such as scandium(III) triflate. For more valuable or sensitive substrates other, milder procedures such as Steglich esterification are used. The reaction is often carried out without a solvent or in a non-polar solvent to facilitate the Dean-Stark method. Typical reaction times vary from 1–10 hours at temperatures of 60-110 °C.

In organic chemistry, an acyl chloride is an organic compound with the functional group −C(=O)Cl. Their formula is usually written R−COCl, where R is a side chain. They are reactive derivatives of carboxylic acids. A specific example of an acyl chloride is acetyl chloride, CH3COCl. Acyl chlorides are the most important subset of acyl halides.

<span class="mw-page-title-main">Acyl halide</span> Oxoacid compound with an –OH group replaced by a halogen

In organic chemistry, an acyl halide is a chemical compound derived from an oxoacid by replacing a hydroxyl group with a halide group.

<span class="mw-page-title-main">Triphosgene</span> Chemical compound

Triphosgene (bis(trichloromethyl) carbonate (BTC) is a chemical compound with the formula OC(OCCl3)2. It is used as a solid substitute for phosgene, which is a gas and diphosgene, which is a liquid. Triphosgene is stable up to 200 °C. Triphosgene is used in a variety of halogenation reactions.

<span class="mw-page-title-main">Acetic anhydride</span> Organic compound with formula (CH₃CO)₂O

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.

<span class="mw-page-title-main">Acetyl chloride</span> Organic compound (CH₃COCl)

Acetyl chloride is an acyl chloride derived from acetic acid. It belongs to the class of organic compounds called acid halides. It is a colorless, corrosive, volatile liquid. Its formula is commonly abbreviated to AcCl.

In chemistry, a dehydration reaction is a chemical reaction that involves the loss of water from the reacting molecule or ion. Dehydration reactions are common processes, the reverse of a hydration reaction.

<span class="mw-page-title-main">Organic acid anhydride</span> Any chemical compound having two acyl groups bonded to the same oxygen atom

An organic acid anhydride is an acid anhydride that is also 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, whereby reaction occurs between two different carboxylic acids. Nomenclature of unsymmetrical acid anhydrides list the names of both of the reacted carboxylic acids before the word "anhydride" (for example, the dehydration reaction between benzoic acid and propanoic acid would yield "benzoic propanoic anhydride").

In organic chemistry, the Arndt–Eistert reaction is the conversion of a carboxylic acid to its homologue. Named for the German chemists Fritz Arndt (1885–1969) and Bernd Eistert (1902–1978), the method entails treating an acid chlorides with diazomethane. It is a popular method of producing β-amino acids from α-amino acids.

<span class="mw-page-title-main">Mercury(II) acetate</span> Chemical compound

Mercury(II) acetate, also known as mercuric acetate is the chemical compound with the formula Hg(O2CCH3)2. Commonly abbreviated Hg(OAc)2, this compound is employed as a reagent to generate organomercury compounds from unsaturated organic precursors. It is a white, water-soluble solid, but some samples can appear yellowish with time owing to decomposition.

<span class="mw-page-title-main">Diphenylketene</span> Chemical compound

Diphenylketene is a chemical substance of the ketene family. Diphenylketene, like most stable disubstituted ketenes, is a red-orange oil at room temperature and pressure. Due to the successive double bonds in the ketene structure R1R2C=C=O, diphenyl ketene is a heterocumulene. The most important reaction of diphenyl ketene is the [2+2] cycloaddition at C-C, C-N, C-O, and C-S multiple bonds.

<span class="mw-page-title-main">Propionic anhydride</span> Chemical compound

Propionic anhydride is an organic compound with the formula (CH3CH2CO)2O. This simple acid anhydride is a colourless liquid. It is a widely used reagent in organic synthesis as well as for producing specialty derivatives of cellulose.

<span class="mw-page-title-main">Meerwein arylation</span> Organic reaction

The Meerwein arylation is an organic reaction involving the addition of an aryl diazonium salt (ArN2X) to an electron-poor alkene usually supported by a metal salt. The reaction product is an alkylated arene compound. The reaction is named after Hans Meerwein, one of its inventors who first published it in 1939.

The Schotten–Baumann reaction is a method to synthesize amides from amines and acid chlorides:

<span class="mw-page-title-main">Ethenone</span> Organic compound with the formula H2C=C=O

In organic chemistry, ethenone is the formal name for ketene, an organic compound with formula C2H2O or H2C=C=O. It is the simplest member of the ketene class. It is an important reagent for acetylations.

<span class="mw-page-title-main">Acetic acid</span> Colorless and faint organic acid found in vinegar

Acetic acid, systematically named ethanoic acid, is an acidic, colourless liquid and organic compound with the chemical formula CH3COOH. Vinegar is at least 4% acetic acid by volume, making acetic acid the main component of vinegar apart from water. It has been used, as a component of vinegar, throughout history from at least the third century BC.

<span class="mw-page-title-main">Acetic formic anhydride</span> Chemical compound

Acetic formic anhydride is an organic compound with the chemical formula C
3
H
4
O
3
, which can be viewed as the mixed anhydride of acetic acid and formic acid. It is used on a laboratory-scale as a formylating agent.

References

  1. 1 2 Seto, E.; Yoshida, M. (2014). "Erasers of Histone Acetylation: The Histone Deacetylase Enzymes". Cold Spring Harbor Perspectives in Biology. 6 (4): a018713. doi:10.1101/cshperspect.a018713. PMC   3970420 . PMID   24691964.
  2. Ali, Ibraheem; Conrad, Ryan J.; Verdin, Eric; Ott, Melanie (2018). "Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics". Chemical Reviews. 118 (3): 1216–1252. doi:10.1021/acs.chemrev.7b00181. PMC   6609103 . PMID   29405707.
  3. Bolden, Jessica E.; Peart, Melissa J.; Johnstone, Ricky W. (2006). "Anticancer activities of histone deacetylase inhibitors". Nature Reviews Drug Discovery. 5 (9): 769–784. doi:10.1038/nrd2133. PMID   16955068. S2CID   2857250.
  4. Shahbazian, Mona D.; Grunstein, Michael (2007). "Functions of Site-Specific Histone Acetylation and Deacetylation". Annual Review of Biochemistry. 76: 75–100. doi:10.1146/annurev.biochem.76.052705.162114. PMID   17362198.
  5. F. K. Thayer (1925). "Acetylmandelic Acid and Acetylmandelyl Chloride". Organic Syntheses. 4: 1. doi:10.15227/orgsyn.004.0001.
  6. Herbst, R. M.; Shemin, D. (1939). "Acetylglycine". Organic Syntheses. 19: 4. doi:10.15227/orgsyn.019.0004.
  7. 1 2 F. E. Ray and George Rieveschl, Jr (1948). "2-Acetylfluorene". Organic Syntheses. 28: 3. doi:10.15227/orgsyn.028.0003.
  8. 1 2 Merritt, Jr., Charles; Braun, Charles E. (1950). "9-Acetylanthracene". Organic Syntheses. 30: 1. doi:10.15227/orgsyn.030.0001.
  9. Denoon, C. E. Jr.; Adkins, Homer; Rainey, James L. (1940). "Acetylacetone". Organic Syntheses . 20: 6. doi:10.15227/orgsyn.020.0006.
  10. Arpe, Hans-Jürgen (2007), Industrielle organische Chemie: Bedeutende vor- und Zwischenprodukte (in German) (6th ed.), Weinheim: Wiley-VCH, pp. 200–1, ISBN   978-3-527-31540-6 [ permanent dead link ]
  11. Balser, Klaus; Hoppe, Lutz; Eicher, Theo; Wandel, Martin; Astheimer, Hans‐Joachim; Steinmeier, Hans; Allen, John M. (2004). "Cellulose Esters". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a05_419.pub2. ISBN   978-3527306732.
  12. Manchand, Percy S. (2001). "Vinyl Acetate". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rv008. ISBN   0471936235.