Acid chlorides acyl transfer

In an acyl group transfer reaction, the acyl group of an acid chloride is transferred from the Cl of the acid chloride to the N of an amine or ammonia. The product is an amide. 

Recently, N-methyliraidazole-mediated KR of racemic secondary alcohols during the transfer of a chiral acyl moiety was developed [41]. This resolution process proceeds via chiral acyl imidazolium chlorides 11 with very good selectivity. The discriminating ability between the enantiomers of alcohols was observed only with the N-methylimidazole derivative and not with the parent acid chloride acyl donor. Various acyl imidazolium chlorides were reacted with racemic alcohols to produce the enantiomerically enriched esters and alcohols. Strong non-covalent cation-Ji interactions in a specific conformation of an intermediate cation-)i complex (parallel stacking) provide high selectivity as shown in 12. 

An important difference between Fnedel-Crafts alkylations and acylations is that acyl cations do not rearrange The acyl group of the acyl chloride or acid anhydride is transferred to the benzene ring unchanged The reason for this is that an acyl cation is so strongly stabilized by resonance that it is more stable than any ion that could con ceivably arise from it by a hydride or alkyl group shift... 

Acyl-transfer reactions are some of the most important conversions in organic chemistry and biochemistry. Recent work has shown that adjacent cationic groups can also activate amides in acyl-transfer reactions. Friedel-Crafts acylations are known to proceed well with carboxylic acids, acid chlorides (and other halides), and acid anhydrides, but there are virtually no examples of acylations with simple amides.19 During studies related to unsaturated amides, we observed a cyclization reaction that is essentially an intramolecular acyl-transfer reaction involving an amide (eq 15). The indanone product is formed by a cyclization involving the dicationic species (40). To examine this further, the related amides 41 and 42 were studied in superacid promoted conversions (eqs 16-17). It was found that amide 42 leads to the indanone product while 41... 

A viable iron carbonyl-mediated reduction process converts acid chlorides and bromoalkanes into aldehydes [3, 6]. Yields are high, with the exception of nitro-benzoyl chloride, and the procedure is generally applicable for the synthesis of alkyl, aryl and a,(i-unsaturated aldehydes from the acid chlorides. The reduction proceeds via the initial formation of the acyl iron complex, followed by hydride transfer and extrusion of the aldehyde (cf. Chapter 8). 

Electrophiles, which lead to high yields, are methyl iodide, trialkyltin- and trialkylsUyl chlorides, diphenylphosphinyl chloride, acid chlorides, aldehydes and carbon dioxide. Remarkably, though highly acidic ketones are formed on acylation, no deprotonation or racemization by excess of carbanionic species occurs. Other alkyl halides than methyl iodide react very sluggishly with low yields. Benzylic and aUylic halides lead to partial racemization, presumably due to single-electron transfer (SET) in the alkylation step. As very recently found by Papillon and Taylor, racemization of 42 can be suppressed by copper-zinc-lithium exchange before alkylation to 43 via the Knochel cuprates (equation 7) °. 

Several polymeric acyl-transfer reactants have been used to give am-ide/ester products in the solution phase. The excess polymer-bound acyl-transfer reactants and polymer-bound nucleofuge byproducts are easily removed after completion of the reactions. One such application involved the activated nitrophenyl esters 25 (reaction 8).40 A mixture of 10 acid chlorides was converted to an equimolar mixture of 10 amide products a potent preemergent herbicide was discovered using this parallel synthetic approach.41... 

BrOP). These active esters react smoothly with amines at room temperature (reaction 9).42 Similarly, supported oximino esters 2743 and hydroxamic esters 2844 undergo facile acyl transfer reactions with amines at room temperature (reaction 10). The spent activating agent can be regenerated many times (by acylation with the appropriate acid chloride) without appreciable loss in activity. 

The acyl group of the carboxylic acid, acyl chloride, or acid anhydride is transferred to the oxygen of the alcohol. This fact is most clearly evident in the esterification of chiral alcohols, where, because none of the bonds to the chirality center is broken in the process, retention of configuration is observed. 

Unfortunately, several important classes of a-diazo ketones cannot be prepared in good yield via these standard methods. a -Diazo derivatives of a.p-unsaturated ketones, for example, have previously proved to be particularly difficult to prepare.1113 12 The acylation of diazomethane with a.p-unsaturated acid chlorides and anhydrides is generally not a successful reaction because of the facility of dipolar cycloaddition to conjugated double bonds, which leads in this case to the formation of mixtures of isomeric pyrazolines. Also problematic are diazo transfer reactions involving base-sensitive substrates such as certain a,p-enones and heteroaryl ketones. Finally, the relatively harsh conditions and lack of regioselectivity associated with the thermodynamically controlled Claisen formylation step in the "deformylative" diazo transfer procedure limit the utility of this method when applied to the synthesis of diazo derivatives of many enones and unsymmetrical saturated ketones. 

Modified Curtius rearrangement. Acyl azides, preferably prepared in situ under phase-transfer conditions by reaction of acid chlorides and NaN, are converted to tri-fluoroacetamides by reaction with CF,COOH in refluxing CH CI, solution. These products are cleaved to primary amines under mild conditions (equation I). ... 

N-Acylsaccharins (13) possess a certain potential as acylating agents. They will acylate amines, but will react with water or alcohols only when acid or base is present.167 The method was used to acylate a-amino-penicillanic acid.170 Micheel162-165 has based a peptide (38) synthesis on the acyl transfer from 31 [Z = carbobenzoxy, obtained through reaction with DCC or with pseudosaccharin chloride (6) or with thionyl chloride and imidazole] to amino acids. Pseudosaccharin anhydride 323, lee js thg product of a condensation between 6 and 1, mostly from hydrolysis of 6. Formation of 32 tends to occur in nonprotic solvents with base catalysis, even when practical precautions are taken to exclude moisture. Water and protic solvents seem to shield the anion 19 and prevent attack on 6. 

Asymmetric Alkylation. 4-Pseudoephedrine ([IS, 2S]-(+)) is a commodity chemical employed in over-the-counter medications with annual worldwide production in excess of 300 metric tons. The enantiomer, /-pseudoephedrine, is also readily available in bulk and is inexpensive. Pseudoephedrine has been shown to be highly effective as a chiral auxiliary in asymmetric alkylation reactions. Treatment of either enantiomer of pseudoephedrine with carboxylic acid chlorides and anhydrides leads to efficient and selective iV-acylation to form the corresponding tertiary amide derivatives (Table 1). Typically, the only by-product in the acylation reactions is a small amount (<5%) of the A,0-diacylated product, which is easily removed by crystallization or flash column chromatography. Because intramolecular 0- -N acyl transfer within pseudoephedrine 3-amino esters occurs rapidly, and because the A-acyl form is strongly favored under neutral or basic conditions, products arising from (mono)acylation on oxygen rather than nitrogen are not observed. 

In Friedel-Crafts acylation, a benzene ring is treated with an acid chloride (RCOCl) and AICI3 to form a ketone. Because the new group bonded to the benzene ring is called an acyl group, the transfer of an acyl group from one atom to another is an acylation. 

The AlCl3 mediated electrophilic substitution of alkynylsilanes with acid chlorides provides a convenient route to alkynyl ketones. Transfer of the acetylenic moiety from silicon to the acyl chloride proceeds via the acyl cation (acylium ion) formed by reaction of the acyl chloride with AlClg. " ... 

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