Acetylation, of alcohols

Although the acetylation of alcohols and amines by acetic anhydride is almost invariably carried out under anhydrous conditions owing to the ready hydrolysis of the anhydride, it has been shown by Chattaway (1931) that phenols, when dissolved in aqueous sodium hydroxide solution and shaken with acetic anhydride, undergo rapid and almost quantitative acetylation if ice is present to keep the temperature low throughout the reaction. The success of this method is due primarily to the acidic nature of the phenols, which enables them to form soluble sodium derivatives, capable of reacting with the acetic... 

Nearly all commercial acetylations are realized using acid catalysts. Catalytic acetylation of alcohols can be carried out using mineral acids, eg, perchloric acid [7601-90-3], phosphoric acid [7664-38-2], sulfuric acid [7664-93-9], benzenesulfonic acid [98-11-3], or methanesulfonic acid [75-75-2], as the catalyst. Certain acid-reacting ion-exchange resins may also be used, but these tend to decompose in hot acetic acid. Mordenite [12445-20-4], a decationized Y-zeohte, is a useful acetylation catalyst (28) and aluminum chloride [7446-70-0], catalyzes / -butanol [71-36-3] acetylation (29). 

The rate constant /ct, determined by means of Eq. (6-47) or (6-48), may describe either general base or nucleophilic catalysis. To distinguish between these possibilities requires additional information. For example, in Section 3.3, we described a kinetic model for the N-methylimidazole-catalyzed acetylation of alcohols and experimental designs for the measurement of catalytic rate constants. These are summarized in Scheme XVIIl of Section 3.3, which we present here in slightly different form. 

The ability of enzymes to achieve the selective esterification of one enantiomer of an alcohol over the other has been exploited by coupling this process with the in situ metal-catalysed racemisation of the unreactive enantiomer. Marr and co-workers have used the rhodium and iridium NHC complexes 44 and 45 to racemise the unreacted enantiomer of substrate 7 [17]. In combination with a lipase enzyme (Novozyme 435), excellent enantioselectivities were obtained in the acetylation of alcohol 7 to give the ester product 43 (Scheme 11.11). A related dynamic kinetic resolution has been reported by Corberdn and Peris [18]. hi their chemistry, the aldehyde 46 is readily racemised and the iridium NHC catalyst 35 catalyses the reversible reduction of aldehyde 46 to give an alcohol which is acylated by an enzyme to give the ester 47 in reasonable enantiomeric excess. 

Metal triflate Lewis acids can also be dispersed in ionic liquids for catalytic applications. Acetylation of alcohols with acetic anhydride and acetic acid has been reported with Cu(OTf)2, Yb(OTf)3, Sc(OTf)3, In(OTf)3, HfClq. (THF)2, and InCl3 in ionic liquids that consist of [BMIM] and the anions BF4, PF, or SbF 166). With lmol% acid, all the catalysts in [BMIMJPF showed >99% acetylation products in acetyl anhydride acetylation of benzyl alcohol. Sc(OTf)3 showed the best yield with recycling, with a 25% drop in yield after two cycles. A relatively long reaction period was needed to obtain a high yield (95-98%) for the acetylation of benzyl alcohol with acetic acid, indicating that the activities of the catalysts were... 

Nafion-H exhibits lower activity. In the acetylation of alcohols,673 in the transformation of aldehydes and ketones with trimethyl orthoformate to the corresponding dimethylacetals,674 and in the formation of acylals,675 longer reaction times (several hours) are required to achieve high yields at room temperature. Furthermore, the formation of ethylenedithioacetals in benzene674 and the direct transformation of acetals to thioacetals with ethane-1,2-thiol in dichloromethane676 can only be performed at reflux temperature. 

S. A. Forsyth, D. R. MacFarlane, R. J. Thomson, and M. von Itzstein, Rapid, clean and mild O-acetylation of alcohols and carbohydrates in a ionic liquid, Chem. Commun. (2002) 714-715. 

Acetylation of alcohol 186 gave the ester 187 in 87% yield after distillation. Claisen rearrangement of 187 with lithium diethylamide as base avoided the usual... 

Sano, T. Ohashi, K. Oriyama, T. Remarkably fast acylation of alcohols with PhCOCl promoted by TMEDA. Synthesis 1999, 1141-1144. Carrigan, M. D. Freiberg, D. A. Smith, R. C. Zerth, H. M. Mohan, R. S. A simple and practical method for large-scale acetylation of alcohols and diols using Bi(OTf)3. Synthesis 2001, 2091-2094. 

Alleti, R., W.S. Oh, M. Perambuduru, Z. Afrasiabi, E. Sinn and V.P. Reddy, Gadolinium Triflate Immobilized in Imidazolium Based Ionic Liquids A Recyclable Catalyst and Green Solvent for Acetylation of Alcohols and Amines, Green Chemistry, 7, 203-206 (2005). 

Forsyth, S.A., D.R. MacFarlane, R.J. Thomson and M. von Itzstein, Rapid, Clean, and Mild O-Acetylation of Alcohols and Carbohydrates in an Ionic Liquid, Chemical Communications, 714-715 (2002). 

Gholap, A.R., K. Venkatesan, T. Daniel, R.J. Lahoti and K.V. Srinivasan, Ultrasound Promoted Acetylation of Alcohols in Room Temperature Ionic Liquid Under Ambient Conditions, Green Chemistry, 5, 693-696 (2003). 

Use of acetic anhydride. Acetic anhydride is inexpensive and convenient to use, and it often gives better yields than acetyl chloride for acetylation of alcohols (to make acetate esters) and amines (to make acetamides). 

A number of Lewis acidic metal salts have been tested in the acetylation of alcohols with acetic anhydride and acetic acid.[67] Of these, copper(II) triflate showed by far the highest activity, but the recycling potential was low. The recyclability was found to be much better with either Sc(OTf)3 or Yb(OTf)3. The reaction between benzyl alcohol and acetic anhydride proceeded to completion within one hour, whereas with acetic acid two days were required under identical reaction conditions. Of the ionic liquids tested, the best activities were obtained in [C4Ciim][PF6]. 

The first example of a Friedel-Crafts type reaction in an ionic liquid medium dates back to 1976 when the electrochemical oxidation of hexamethylbenzene in [C2py]Br-AlCl3 afforded a mixture of alkylated polyphenyl compounds.[69] Other early examples include the alkylation of benzene in C2Ciim C1-A1C137 and the acylation of ferrocene in [C2Ciim]I-AlClJ71 There are now numerous examples of Lewis- or Bronsted acid-catalysed Friedel-Crafts type reactions in ionic liquids. These include alkylation,[72 76] acylation,[71,77"83] arylation,[77 841 sulfonylation,[851 sulfoamylation[86] and O-acetylation of alcohols.[87,881... 

Heravi, M.M., Behbahani, F.K., and Bamoharram, F.F. 2006b. H14[NaP5W300110] A heteropolyacid catalyzed acetylation of alcohols and phenols in acetic anhydride. Journal of Molecular Catalysis A Chemical, 253 16-19. 

Das B, Thirupathi P (2007) A Highly Selective and Efficient Acetylation of Alcohols and Amines with Acetic Anhydride Using NaHS04.Si02 as a Heterogeneous Catalyst. J Mol Catal A Chem 269 12... 

Acetylation of alcohols and phenols by ketene has limited use. Unless apparatus for the preparation of ketene is readily available, less troublesome methods can usually be found. Worthy of mention, however, are the acetylations of lactic esters in 94-98% yields and of tertiary alcohols and phenols in 89-96% yields.Catalysts are necessary even to convert a high percentage of n-butyl alcohol to n-butyl acetate. Sulfuric and p-toluenesulfonic acids are commonly used. Certain aldehydes and ketones are attacked by ketene. Acetates of enol forms of ketones may be made in this way. ° Under certain conditions / -lactones are formed (cf. method 327),... 

Protection and deprotection oj 0-acetylation of alcohols and accu Trityl ethers are cleaved by ITV not affected. Discrimination of ary l (alkyl TBS ethers are selectively hy such amides by brief treatment witf Thioacetals are converted to car lodinations. In the preparat added. lodination of aromatic 1 -(tosyloxy)-1,2-benziodoxol-3( 1H iodination of 3,4-bis(trimethylsilyl i a combination of iodine and sih unsymmetrical 3,4-diarylthiophene a-Methoxy-a,P-unsaturated et (1 -methoxyalkylidene)-mngsten(O) the unsaturated esters. When iodim low. 

Acetylation. Sulfamic acid is an excellent catalyst for acetylation of alcohols (including phenols) with acetic anhydride at room temperature. 

Functional group protections. Effective mediation by TaClj/SiOj is noted in the acetylation of alcohols and the formation of phthalimides from amines and phthalic anhydride, the latter process assisted by microwaves. The catalyst system is also useful for tetrahydropyranation of alcohols and dithioacetalizadon of aldehydes. ... 

Esterification. Formylation and acetylation of alcohols can be effected using... 

Acetylation. The reagents can be used for the acetylation of alcohols, phenols, and amines and for Friedel-Crafts acetylation of reactive aromatics. In general 2-acetoxypyridine is more reactive than the 3-isomer. 

Acetylation. The reagent, neat or in nitromethane solution, acylatcs aromatic compounds in good yield (I). It is an effective reagent for O-acetylation of alcohols (2), for S-acetylation of mercaptans, and for N-acetylation of primary and secondary amides. 

Forsyth SA, MacFarlane DR, Thomson RJ, von Itzstein M (2002) Rapid, clean, and mild 0-acetylation of alcohols and carbohydrates in an ionic liquid. Chem Commun 7 714-715... 

The acetylation of alcohols and phenols with acetic anhydride and HSZ-360 zeolite at 60oC used no solvent. The acetate of 1-dodecanol was obtained in 98% yield, and the acetate from 1 naphthol in 100% yield.183 The acylation of anisole with acetic anhydride at 100oC without solvent using zeolite H-/8 gave 4-methoxyacetophenone (6.30) in 98%yield.184 The catalyst could be recovered, regenerated, and reused with no decrease in yield. These reactions show that not all zeolites are used at high temperatures in the vapor phase. 

Acetylation. The acetylation of alcohols (including phenols), thiols, and amines by acetic anhydride is catalyzed by LiCl. 

Allylation. TaCls is useful for promoting allylation of aldehydes with allyl-trimethylsilane as well as acetylation of alcohols, therefore these two reactions can be achieved without isolation of the homoallylic alcohols. 

Reactions. Various types of zeolites continue to be exploited as catalysts or supports for common transformations acetylation of alcohols with HO Ac, reduction of... 

Protecting-group manipulations. Tetrahydropyranyl ethers are switched to t-butyldimethylsilyl ethers on reaetion of RjSiOTf and EtjN in dichloromethane at room temperature. f-Butyl esters also undergo group exchange in the presence of t-butyl ethers. IV-r-Butoxycarbonyl derivatives of primary amines are further silylated with M SiOTf to give the base stable produets. Rapid acetylation of alcohols is promoted by the same catalyst. ... 

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