Acylation by acid anhydrides

Baddeley and Voss also showed that the aluminium halide-catalysed acylation by acid anhydrides proceeds via the initial formation of the acyl halide, equilibrium (200)... 

The inclusion of DMAP to the extent of 5-20 mol % in acylations by acid anhydrides and acyl chlorides increases acylation rates by up to four orders of magnitude and permits successful acylation of tertiary and other hindered alcohols. The reagent combination of an acid anhydride with MgBr2 and a hindered tertiary amine, e.g., ( -Pr)2NC2H5 or 1,2,2,6,6,-pentamethylpiperidine, gives an even more reactive acylation system, which is useful for hindered and sensitive alcohols.105... 

Magnesium enolates play an important role in C-acylation reactions. The magnesium enolate of diethyl malonate, for example, can be prepared by reaction with magnesium metal in ethanol. It is soluble in ether and undergoes C-acylation by acid anhydrides and acyl chlorides (entries 1 and 3 in Scheme 2.14). Monoalkyl esters of malonic acid react with Grignard reagents to give a chelated enolate of the malonate monoanion. 

The inclusion of DMAP to the extent of 5-20 mol% in acylations by acid anhydrides and acyl chlorides increases acylation rates by up to four orders of magnitude and permits successful acylation of tertiary and other hindered alcohols. 

Pyrrole and alkylpyrroles are acylated by acid anhydrides above 100°C. Pyrrole itself gives a mixture of 2-acetyl- and 2,5-diacety 1-pyrrole on heating with acetic anhydride at 150-200°C. N-Acylpyrroles are obtained by reaction of the alkali metal salts of pyrrole with an acyl halide. iV-Acetylimidazole efficiently acetylates pyrrole on nitrogen (65CI(L)1426). Pyrrole-2-carbaldehyde is acetylated on nitrogen in 80% yield by reaction with acetic anhydride in methylene chloride and in the presence of triethylamine and 4-dimethylaminopyridine (80CB2036). 

Homophthalic acids are acylated by acid anhydrides in the presence of pyridine, producing 4-acylisochroman-l,3-diones (494) (80CB3927). Rearrangement to a 3-alkylisocoumarin-4-carboxylic acid (495) occurs in acid solution and may be accompanied by decarboxylation. 

The acylation of aromatic ethers by acyl chlorides is highly regioselective in the presence of 10 mol% Sml3.53 Some aromatic compounds are efficiently acylated by acid anhydrides catalysed by niobium pentachloride with silver perchlorate.54 Arenes of a range of reactivity are acylated by acetic anhydride in a fluorous biphasic system catalysed by Hfps SCLCgFn L (1 mol%)55 The catalyst is easily recoverable and can usually be used again without decrease in activity. 

Acylation by acid anhydrides also prevents somerization, but Ihis is wastelut ot reagent, since half of If IS converted into the cartao> ylic acid, and is therefore economicafly unacceptable. Nevertheless, cyclic anhydrides are viable reagents, as m the Haworth reaction (see Chapter 12). 

SpN 495 was also acylated by acid anhydride, benzoyl chloride, benzyl chloro-formate, potassium cyanate, and phenyl isocyanate to give 593-596 (91JHC97). 

Amides are readily prepared by acylation of ammonia and amines with acyl chlorides acid anhydrides or esters... 

Nucleophilic acyl substitution (Sections 20 4 20 6 and 20 12) Acylation of am monia and amines by an acyl chloride acid anhydride or ester is an excep tionally effective method for the for mation of carbon-nitrogen bonds... 

Ketone Synthesis. In the Friedel-Crafts ketone synthesis, an acyl group is iatroduced iato the aromatic nucleus by an acylating agent such as an acyl haUde, acid anhydride, ester, or the acid itself. Ketenes, amides, and nittiles also may be used aluminum chloride and boron ttitiuotide are the most common catalysts (see Ketones). 

Methylation of 1-hydroxyindoles can be achieved readily by the reaction with diazomethane, Mel, orMc2S04 in the presence of an appropriate base, as described in previous reviews (79MI1, 90AHC105, 91YGK205, 99H1157). Alkylation and acylation also work well with alkyl halides, acyl halides, acid anhydrides, and acids in the presence of acid activators such as DCC and so on. 

Primary and secondary amines are acylated by acid chlorides and anhydrides, in particular also by the chloride of benzene sulphonic add (p. 192). The preparation of acetanilide has already been described (pp. 125, 128). The acetyl- and benzoyl-derivatives of all the simpler primary amines of the benzene and naphthalene series are known, so that these derivatives can always serve for purposes of identification. 

Acylaminocarboxylic acids 288 are converted into 5(4//)-oxazolinones 289 by acid anhydrides (Scheme 140). In an extension of this reaction, A-acyl derivatives of glycine 290 react with aldehydes with concomitant cyclization to give azlactones 291 (Scheme 141) this is the basis of the Erlenmeyer synthesis of amino acids. Treatment of amino acid derivatives 292 with PBr3 affords the thiazolidine-2,5-dione 293 (Scheme 142) <1971CB3146>. 

The selenophene ring may be acylated by acyl chlorides under Friedel-Crafts conditions7 63 by acid anhydrides in the presence of 85% phosphoric acid64 and by organic silicoanhydrides (tetraacyloxy-silanes) in the presence of stannic chloride.65-67 When acylated by silicoanhydrides of dibasic organic acids (succinic, adipic, azelaic, or... 

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