Acylium ions formation

Thus, the best compromises for Boc and Fmoc chemistries seem to be cyclohexyl and 2,4-dimethylpent-3-yl (Dmpn), which is of intermediate stability, and the removal of which by trifluoromethanesulfonic acid with the aid of thioanisole (see Section 6.22) leads to minimal imide formation (see Section 6.13). Points to note are that acidolysis of esters by hydrogen fluoride can lead to fission at the oxy-car-bonyl bond instead of the alkyl-oxy bond, thus generating acylium ions that can react with nucleophiles (see Sections 6.16 and 6.22), and that benzyl esters may undergo transesterification if left in methanol. The side reactions of cyclization (see Section 6.16) and acylation of anisole (see Section 6.22) caused by acylium ion formation do not occur at the side chain of aspartic acid.47-51... 

In contrast to this demonstration of bimolecularity, Hall and Lueck82 showed the possibility of acylium ion formation from benzoyl chloride by its reaction with mercuric perchlorate. In common with dimethylcarbamyl chloride, dimethylsulphamyl and tetramethyldiamidophosphochloridate, benzoyl chloride reacted readily to form the corresponding acylium ion /i-butyl chloroformate however was inert. Kivinen138 studied the effect of mercuric chloride on the ethanolysis of 4-methoxybenzoyl chloride, benzoyl chloride and 4-nitrobenzoyl chloride and obtained the following approximate relative rates for the effect of mercuric chloride (0.30 M) in ethanol, 4-MeO, 2.91 4-H, 1.00 4-NOz, 1.03, confirming the SN2 character of the 4-nitro-... 

Ladenheim, H., Bender, M. L. (1960). Acylium Ion Formation in the Reactions if Carboxylic Acid Derivatives. /. Application of the HR Acidity Function to the Diazotization ofBenzamide in Sulfuric Acid. Journal of the American Chemical Society, 82, 1895-1900. 

The trapping of an a,p-unsaturated ketone as its enol acetate, by acylium ion formation with chlorotrimethylsilane and acetic anhydride. 

There are other possibilities besides a T.L, such as acylium ion formation, ketene formation, and direct displacement analogous to an Sn2 reaction (Figure 10.16). Such mechanisms are viable under certain conditions. Acylium ions are formed with acid halides, esters, and some amides under highly acidic conditions, and acid halides can form ketenes with base catalysis. However, by far the most common pathway is addition-elimination via a tetrahedral intermediate. Let s examine the evidence for this intermediate. 

Note that h3 erconjugative interaction with the carbonyl group is not destroyed during acylium ion formation, since of the two mutually perpendicular antisymmetric combinations of CH bond orbitals one remains parallel to the CO TT-bond and the other interacts with the vacant p orbital. It is not implied that the transition state approximates to the free acetylium ion, or that the latter is ever formed during the reaction. It is sufficient that the transition state involve little or no covalent bond formation with water, and extensive delocalization of the TT-electrons without full development of positive charge. 

Mass Spectrometry Aldehydes and ketones typically give a prominent molecular ion peak m their mass spectra Aldehydes also exhibit an M— 1 peak A major fragmentation pathway for both aldehydes and ketones leads to formation of acyl cations (acylium ions) by cleavage of an alkyl group from the carbonyl The most intense peak m the mass spectrum of diethyl ketone for example is m z 57 corresponding to loss of ethyl radi cal from the molecular ion... 

Oxidative Ring Closure Reactions 4.03.4.1.1 C—N bond formation N—N bond formation C—S bond formation N—S bond formation O—C bond formation O—N bond formation S—S, S—Se and Se—Se bond formation Electrophilic Ring Closures via Acylium Ions and Related Intermediates Ring Closures via Intramolecular Alkylations... 

The formation of acyl halide-Lewis acid complexes have been observed by several methods. For example, both 1 1 and 1 2 complexes of acetyl chloride, with AICI3 can be observed by NMR spectroscopy. The existence of acylium ions has been demonstrated by X-ray diffraction studies on crystalline salts. For example, crystal structure determinations have been reported for /i-methylphenylacylium and acetylium ions as SbFg salts. There is also a good deal of evidence from NMR measurements which demonstrates that acylium ions can exist in nonnucleophilic solvents. " The positive charge on acylium ions is delocalized onto the oxygen atom. This delocalization is demonstrated in particular by the short O—C bond lengths in acylium ions, which imply a major contribution from the structure having a triple bond ... 

The reaction is initiated by formation of a donor-acceptor complex 4 from acyl chloride 2, which is thereby activated, and the Lewis acid, e.g. aluminum trichloride. Complex 4 can dissociate into the acylium ion 5 and the aluminum tetrachloride anion 4 as well as 5 can act as an electrophile in a reaction with the aromatic substrate ... 

The formation of the acylium ion from esters is favored by electron-withdrawing groups in the alcohol and electron-releasing groups in the... 

There is no reason to believe that any of these reactions involve formation of an intermediate acylium ion (Bentley et al., 1984) but the extent of C—Cl bond breaking probably increases markedly with increasing electron release from a substituent. Kinetic primary chloride isotope effects show that C—Cl bond breaking increases with increasing electron release in hydrolyses of 4-substituted benzoyl chlorides in aqueous acetone (Fry, 1970)... 

The cleavage of C5-C4 and formation of C5-C3 suggests that we have a 1,2-alkyl migration of C5 from C4 to a cationic C3. Then the electrons in the C2-C3 bond can move to form a new n bond between C3 and C4, leaving a stabilized acylium ion at C2. After addition of H2O to the acylium ion, an acid-catalyzed electrophilic addition of the resultant carboxylic acid to the alkene occurs to give the final product. 

Fig. 5.7. The acid-catalyzed hydrolysis of penicillins involves first the formation of an acylium ion (5.22), which, by reacting with H20, yields penicil-loic acids 5.24 (Pathway b). The participation of a neighboring 6-acylamido group increases the rate of hydrolysis. During this intramolecular reaction (Pathway a), oxazolylthiazolidines (5.23) are formed and then give rise to the degradation products penicilloic acids 5.24, penicillenic acids 5.25,...

The origin of the m/z 43 peak in the El mass spectrum of acetone should be quite clear now and we may examine the formation of the ion, m/z 15, next. In principle the ionic charge may reside on either fragment, the acyclium or the alkyl. In case of acetone, the formation of the acylium ion, CHsCO", m/z 43, is preferred... 

In Friedel-Crafts acylations, an acyl halide, almost always the chloride, in the presence of a Lewis acid is employed to acylate an aromatic ring. The process is initiated by polarization of the carbon-chlorine bond of the acyl chloride, resulting in formation of a resonance-stabilized acylium ion. 

A mechanistically significant feature of this reaction is the kinetic preference for formation of jS,y-unsaturated ketones. It has been suggested that this regiochemistry results from an intramolecular deprotonation, as shown in the mechanism above.5 A related reaction occurs between alkenes and acylium ions, as in the reaction between 2-methylpropene and... 

Both the reactions are essentially the additions of iodine carboxylate (formed in situ) to an alkene, i.e., the reaction of an alkene with iodine and silver salt. The Prevost procedure employs iodine and silver carboxylate under dry conditions. The initially formed transiodocarboxylate (b) from a cyclic iodonium ion (a) undergoes internal displacement to a common intermediate acylium ion (c). The formation of the diester (d) with retention of configuration provides an example of neighbouring group participation. The diester on subsequent hydrolysis gives a trans-glycol. 

Under nonequilibrium conditions the p,y-unsaturated ketone tends to predominate, which may be transformed to the more stable conjugated isomer. The intermediacy of 15 may allow further rearrangements to occur. However, acylation with preformed acylium ions, such as acetyl hexachloroantimonate, and in the presence of a base to prevent isomerization, affords exclusive formation of P,y-unsaturated ketones.109 This led to the suggestion of an ene reaction between the acylium ion and the alkene as a possible mechanistic pathway ... 

The existence of acylium ions in the reactions of acyl halides with Lewis acids has been amply demonstrated88,89, but they have not so far been directly observed in hydrolysis reactions. To achieve direct observation of an acylium ion, it must, at best, be generated into a non-reactive environment if its rate of formation is slow, or be detectable in small concentrations if it is destroyed rapidly. The limiting factors are, therefore, the rate and mechanism of heterolysis and the stability and concentration of the acylium ion formed. In this... 

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