Carbonium ions, acylation

The initiating step in these reactions is the attachment of a group to the sulfoxide oxygen to produce an activated intermediate (5). Suitable groups are proton, acyl, alkyl, or almost any of the groups that also initiate the oxidations of alcohols with DMSO (40,48). In a reaction, eg, the one between DMSO and acetic anhydride, the second step is removal of a proton from an a-carbon to give an yUde (6). Release of an acetate ion generates the sulfur-stabilized carbonium ion (7), and the addition of acetate ion to the carbonium ion (7) results in the product (eq. 15) ... 

In this reaction, three steps, ie, acylation, cyclization, and replacement of the chlorine atom by the hydroxyl group, take place simultaneously in concentrated sulfuric acid. In the course of cyclization 2,7-dichlorofluoran (31) may be formed as a by-product presumably through the carbonium ion (30) ihustrated as follows. The addition of boric acid suppresses this pathway and promotes the regular cyclization to form the anthraquinone stmcture. The stable boric acid ester formed also enables the complete replacement of chlorine atoms by the hydroxyl group. Hydrolysis of the boric acid ester of quinizarin is carried out by heating in dilute sulfuric acid. The purity of quinizarin thus obtained is around 90%. Highly pure product can be obtained by sublimation. 

Although in general azoles do not undergo Friedel-Crafts type alkylation or acylation, several isolated reactions of this general type are known. 3-Phenylsydnone (120) undergoes Friedel-Crafts acetylation and Vilsmeier formylation at the 4-position, and the 5-alkylation of thiazoles by carbonium ions is known. 

The acyl residue controls the formation and stability of the carbonium ion. If the carbonium ion is destabilized (by electron withdrawing groups), then cyclization to the phenanthridine nucleus will be sluggish. The slower the rate of cyclization, the greater the chance of side reactions with the cyclization reagent. Therefore, the yield of the phenanthridine will depend on the relative rates of cyclization and side reactions, which is controlled by the stability of the carbonium ion. 

Esters of diphenylacetic acids with derivatives of ethanol-amine show mainly the antispasmodic component of the atropine complex of biologic activities. As such they find use in treatment of the resolution of various spastic conditions such as, for example, gastrointestinal spasms. The prototype in this series, adiphenine (47), is obtained by treatment of diphenyl acetyl chloride with diethylaminoethanol. A somewhat more complex basic side chain is accessible by an interesting rearrangement. Reductive amination of furfural (42) results in reduction of the heterocyclic ring as well and formation of the aminomethyltetrahydro-furan (43). Treatment of this ether with hydrogen bromide in acetic acid leads to the hydroxypiperidine (45), possibly by the intermediacy of a carbonium ion such as 44. Acylation of the alcohol with diphenylacetyl chloride gives piperidolate (46). ... 

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

Olivier and Berger335, who measured the first-order rate coefficients for the aluminium chloride-catalysed reaction of 4-nitroben2yl chloride with excess aromatic (solvent) at 30 °C and obtained the rate coefficients (lO5/ ) PhCI, 1.40 PhH, 7.50 PhMe, 17.5. These results demonstrated the electrophilic nature of the reaction and also the unselective nature of the electrophile which has been confirmed many times since. That the electrophile in these reactions is not the simple and intuitively expected free carbonium ion was indicated by the observation by Calloway that the reactivity of alkyl halides was in the order RF > RC1 > RBr > RI, which is the reverse of that for acylation by acyl halides336. The low selectivity (and high steric hindrance) of the reaction was further demonstrated by Condon337 who measured the relative rates at 40 °C, by the competition method, of isopropylation of toluene and isopropylbenzene with propene catalyzed by boron trifluoride etherate (or aluminium chloride) these were as follows PhMe, 2.09 (1.10) PhEt, 1.73 (1.81) Ph-iPr, (1.69) Ph-tBu, 1.23 (1.40). The isomer distribution in the reactions337,338 yielded partial rate factors of 2.37 /mMe, 1.80 /pMe, 4.72 /, 0.35 / , 2.2 / Pr, 2.55337 339. 

The reaction between carbonium ions and carbon monoxide affording oxocarbonium ions (acyl cations) is a key step in the well-known Koch reaction for making carboxylic acids from alkenes, carbon monoxide and water ... 

Sometimes acylium ions lose carbon monoxide to generate an ordinary carbonium ion. It will be recalled that free acyl radicals exhibit similar behavior at high temperatures. Whether or not the loss of carbon monoxide takes place seems to depend on the stability of the resulting carbonium ion and on the speed with which the acylium ion is removed by competing reactions. Thus no decarbonylation is observed in Friedel-Crafts reactions of benzoyl chloride, the phenyl cation being rather unstable. But attempts to make pivaloyl benzene by the Friedel-Crafts reaction produce tert-butyl benzene instead. With compound XLIV cyclization competes with decarbonylation, but this competition is not successful in the case of compound XLV in which the ring is deactivated.263... 

Reaction of the carbonium ion with water could be reduced if overlap occurred with the carboxylate anion of aspartic acid-52 either during or after the glycoside-cleavage step. Since the carboxylate anion would be held adjacent to the carbonium ion in the active site, equilibrium should be far to the side of the acylal. Reaction of acylal with H2O would then very probably be ratedetermining in the forward direction. Evidence has been obtained that the solvent is directly involved in the hydrolysis of the cyclic acylal 2-(p-nitrophenoxy)phthalide where steric factors are similar... 

While the rates of alkaline and pH-independent hydrolysis of [93] and [94] are similar, hydronium ion catalysis is 2500 times less favourable in the case of the cyclic acylal. The large rate difference in comparison with the open chain analogue may reflect the fact that, if a carbonium ion intermediate with a carboxyl group held rigidly adjacent to the carbonium carbon atom were formed in an A-1 reaction, rapid reclosure of the ring would result from recapture of the carbonium carbon by the carboxyl group [equation (55)]. A greatly diminished rate of hydrolysis would result. Perhaps there is a... 

Other hand, reactions catalysed by lysozyme are readily reversible, as shown by the occurrence of transglycosidation. The simplest explanation is that an acylal intermediate is not produced in the rate-determining step. Formation of an acylal after the ratedetermining step by carbonium ion capture by the aspartate anion is an attractive possibility in explaining transglycosidation but should lead to detectable concentrations of acylal. 

A reaction in which an electrophile participates in het-erolytic substitution of another molecular entity that supplies both of the bonding electrons. In the case of aromatic electrophilic substitution (AES), one electrophile (typically a proton) is substituted by another electron-deficient species. AES reactions include halogenation (which is often catalyzed by the presence of a Lewis acid salt such as ferric chloride or aluminum chloride), nitration, and so-called Friedel-Crafts acylation and alkylation reactions. On the basis of the extensive literature on AES reactions, one can readily rationalize how this process leads to the synthesis of many substituted aromatic compounds. This is accomplished by considering how the transition states structurally resemble the carbonium ion intermediates in an AES reaction. 

N-acylamino acids does not appear to have been studied previously. In solution, N-acyl-N-nitroso-a-amino acids are moderately stable to weak bases, such as triethylamine or sodium carbonate, but are decomposed rapidly at 0° to expel nitrogen on addition of sodium hydroxide (43). For example, treatment of N-nitroso-N-benzoyl-D,L-pheny1-alanine LXIIb with an aqueous sodium hydroxide solution at 0 gives benzoic acid and 1-hydroxy-3-phenylpropanoic acid LXVa in a 93% yield. The facile base-catalysed formations of a-hydroxy acids LXV are a general reaction and probably occur by intramolecular attack as shown in LXII->LXIII->LXIV. Oxadiazolone LXIV can decompose by various possible pathways to give LXV among which the carbonium ion pathway is least likely. 

Presence of a phenyl 6ubetitu nt at C(jj, as in 2,3-epoxy-3-phemy) -cyclohexanone caused a preponderance of acyl migration (Eq. 47. j. presumably by stabilizing the carbonium ion generated by Cjar bond rupture. Formation of a oerbonium ton at Ct ) rather than is favored also on electrostatic grounds by the proximity of C( to tlie positive terminal of the carbonyl dipole.8 ... 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

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