Ketene, acylating reactions

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

The intermediacy of ketenes in some enamine acylation reactions using acid chlorides was described above (386,387). Direct addition of ketene to enamines was studied simultaneously by several groups (414-420). The initially formed aminocyclobutanone products could be isolated in some instances, depending on the substitution of the initial enamine. Opening to give either the acylated enamine or the alternative vinylogous amide was found to occur spontaneously or on heating, particularly in adducts derived from enamines with an olefinic proton. 

Neier and coworkers have shown that piperidine diones (e.g., 105) can be prepared stereoselectively using a cascade Diels-Alder/acylation reaction of ketene acetal 104 <96T(52)11643>. 

Alternative catalytic asymmetric acylation reactions studied prochiral silyl imi-noketenes 89 [110] (Fig. 44, top) and silyl ketene acetals 90 [111, 112] (Fig. 44, middle), leading to the formation of quaternary stereocenters. Furthermore, the... 

This effect has recently been explained by considering that under microwave irradiation the route involving direct reaction between the acyl chloride and the imine competes efficiently with the ketene-imine reaction pathway, a situation highlighted by theoretical calculations (Scheme 9.69) [42 a],... 

Intramolecular acylation reactions with ketene complexes, generated, for instance, by thermolysis or photolysis of carbene complexes, can also be used for the preparation of six-membered rings. Illustrative examples are shown in Table 2.23. 

Further methods for preparing seven-membered rings with the aid of heteroatom-substituted carbene complexes include the intramolecular acylation reactions with ketene complexes discussed in Section I.2.6.2. 

There are many reactions in which pyridines are used as bases. However in a large number of reactions only pyridine itself is reactive. a-Substituted pyridines behave differently, e.g. in the catalysis of acylation reactions with acyl chlorides or anhydrides [45]. The sterical hinderance of the a-substituents decelerates reactions in which a pyridine reacts as a nucleophile. A reaction which can be base-catalyzed by a-substituted pyridines is the addition of alcohols to hetero-cumulenes such as ketenes and isocyanates. Therefore this reaction was investigated as a model reaction for base catalysis by concave pyridines. 

On HY, phenylacetate dissociates into phenol and ketene (reaction a). Ortho-hydroxyacetophenone is produced partly by the Fries rearrangement of phenylacetate (intramolecular reaction, reaction b) and by trans-acylation (reaction c) while para-hydroxyacetophenone is exclusively the result of trans-acylation (reaction d). Phenylacetate can also disproportionate into phenol and acetoxyacetophenones (reaction e). Para-acetoxyacetophenone can also be formed through transesterification between para-hydroxyacetophenone and phenylacetate (reaction f).The formation of secondary products like 2-methylchromone and 4-methylcoumarine is consecutive to the formation of... 

This chapter covers the kinetic resolution of racemic alcohols by formation of esters and the kinetic resolution of racemic amines by formation of amides [1]. The desymmetrization of meso diols is discussed in Section 13.3. The acyl donors employed are usually either acid chlorides or acid anhydrides. In principle, acylation reactions of this type are equally suitable for resolving or desymmetrizing the acyl donor (e.g. a meso-anhydride or a prochiral ketene). Transformations of the latter type are discussed in Section 13.1, Desymmetrization and Kinetic Resolution of Cyclic Anhydrides, and Section 13.2, Additions to Prochiral Ketenes. 

Fu has demonstrated that acetate anion attack on the silicon center of the silyl ketene acetal, as well as formation of an acyl pyridinium salt, contribute towards the promotion of these reactions [62]. Additionally, silyl ketene imines have also been shown to participate in analogous asymmetric C-acylation reactions to yield chiral quaternary nitriles, and this method was employed as a key step in the synthesis of verapamil [65]. 

Acid anhydrides in the presence of basic catalysts can be used instead of acyl chlorides in acylation reactions of thiols.Mixed anhydrides of N-protected amino acids and ethyl carbonate yield the corresponding S-f-butyl thiocarboxylic esters, which are useful reagents for peptide syntheses (equation 22). Acylation of thiols with ketenes (equation 23) is a method of long standing. In many cases the yields are nearly quantitative. Functionalities such as acetamino groups or carbon-carbon double bonds in the thiol are not attacked under the mild reaction conditions and optically active thiol esters are obtained without racemization. 3 ... 

Reactions. This reactive ketene acylates hindered amines to produce amides in almost quantitative yield. Tertiary alcohols are converted into esters this reaction is strongly catalyzed by boron trifluoride etherate. 

Acyl sulfenes, like all sulfenes, prefer to participate as 2ir components of [2 -I- 2] or [4 + 2] cycloadditions (Chapter 5). Nonetheless, a range of [4 -I- 2] cycloaddition reactions of acyl sulfenes have been described - (Scheme 8-XII), including their 47t participation in dimerization reactions and reactions with imines, carbodiimides, ketenimines, 1-azirines, vinyl ethers,and ketenes. The reactions often provide mixtures of [4 + 2] and [2 + 2] cycloadducts, and the observed course of the reaction usually depends on the reaction conditions. Consequently, many of the observed [4 + 2] cycloadditions of acyl sulfenes proceed by a stepwise, polar addition-cyclization reaction. 

The ability of iron(iii) chloride to genuinely catalyze Friedel-Crafts acylation reactions has also been recognized by HOlderich and coworkers [76]. By immobilizing the ionic liquid [BMIM]Cl-FeQ3 on a solid support HOlderich was able to acetylate mesitylene, anisole and m-xylene with acetyl chloride in excellent yield. The performance of the iron-based ionic liquid was then compared with the corresponding chlorostannate(ii) and chloroaluminate(iii) ionic liquids. The results are given in Scheme 5.2-30 and Table 5.2-3. As can be seen, the iron catalyst gave superior results to the aluminum or tin-based catalysts. The reactions were also carried out in the gas phase at between 200 and 300 °C. The acetylation reaction was complicated by two side reactions. For example, in the reaction of acetyl chloride with m-xylene, the decomposition of acetyl chloride to ketene and the formation of l-(l-chlorovmyl)-2,4-dimethylbenzene were also found to occur [76]. 

Preparation of Carboxylic Acid Chlorides (and Anhydrides). Oxalyl chloride has found general application for the preparation of carboxylic acid chlorides since the reagent was introduced by Adams and Ulich. Acid chlorides produced by this means have subsequently featured in the synthesis of acyl azides, bromoalkenes, carboxamides, cinnolines, diazo ketones, (thio)esters, lactones, ketenes for cycloaddition reactions, intramolecular Friedel-Crafts acylation reactions, and the synthesis of pyridyl thioethers. ... 

Although crotonic acid, or 2-pentenoic acid from HV comonomer, is the main decomposition product from the biopolymers at low temperature, other degradation products appear under high-temperature pyrolysis conditions. For PHB homopolymer these include propene and carbon dioxide from the breakdown of crotonic acid itself, isocrotonic acid from the obvious reorganization reaction and /3-butyrolactone as a short-lived intermediate that spontaneously decomposes by 0-alkyl scission to propene and carbon dioxide or by O-acyl scission to acetaldehyde and ketene. Similar reactions can be proposed for the comonomer decomposition and some pyrolysis experiments have already been reported. ... 

Bis(trifluoromethyl)keten reacts very readily in non-polar solvents with secondary alkylphosphines and with dialkyl phosphites by P-acylation, reactions which provide easily accessible routes to hexafluoroisobutyryl-phosphines and phosphates. 

The total synthesis of nocardicin A and its analogues has received considerable attention. One of the first approaches 11,14) made use of the classical keten-imine reaction for construction of the P-lactam ring. Reaction of phthalimido-acetyl chloride with the thioimidate (13) in the presence of triethylamine gave the P-lactam (14). Removal of the sulphvu grouping and deprotection afforded 3-ANA, which could be acylated with the appropriate side-chain acid to give nocardicins D, E and G. Reaction of nocardicin D with hydroxylamine produced nocardicin A. Alternative routes 15,16) utilise triazines such as (15) to provide a source of the imines of type (16). This sequence also removes the necessity of a desulphurisation step. 

Tertiary phosphines are known to behave as Lewis bases in acylation reactions that proceed through a nucleophilic activation mechanism (see Section 4.06.7 for possible mechanisms operating in organocatalyzed polymerization). Their use as nucleophilic catalysts in enantioselective processes, which include the addition of alcohols to ketenes, the rearrangement of O-acylated azlactones, and the kinetic resolution of alcohols, is also well documented. " ... 

Acylation of both aromatic and aliphatic compounds can be carried out with relative ease using acyl halides, acid anhydrides, ketenes, nitriles, amides, acids and esters in the presence of Friedel-Craft catalysts to give ketones. Similar substitution reactions with formic acid derivatives are therefore expected to yield the appropriate aldehydes. However, since the anhydride and acyl halides of formic acid, with the exception of formyl fluoride, are either not known or are not sufficiently stable to be used in Friedel-Crafts type acylation reactions, this objective cannot be fully realized. Table 1.1 compares the main ketone syntheses (based on acylating reagents) with the corresponding aldehyde syntheses (based on formylating reagents). 

Allylic phosphates are used for carbonylation in the presence of amines under pressure. Carbonylation of diethyl neryl phosphate (389) affords ethyl homonerate (390), maintaining the geometric integrity of the double bond[244]. The carbonylation of allyl phosphate in the presence of the imine 392 affords the /3-lactam 393. The reaction may be explained by the formation of the ketene 391 from the acyl phosphate, and its stereoselective (2 + 2] cycloaddition to the imine 392 to give the /3-lactam 393(247],... 

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