Acetoxylations

The kinetics of nitration in acetic anhydride are complicated. In addition to the initial reaction between nitric acid and the solvent, subsequent reactions occur which lead ultimately to the formation of tetranitromethane furthermore, the observation that acetoxylation accompanies the nitration of the homologues of benzene adds to this complexity. 

Acetoxylation and nitration. It has already been mentioned that 0- and m-xylene are acetoxylated as well as nitrated by solutions of acetyl nitrate in acetic anhydride. This occurs with some other homologues of benzene, and with methyl phenethyl ether,ii but not with anisole, mesitylene or naphthalene. Results are given in table 5.4. 

The addition of sulphuric acid increased the rate of nitration of benzene, and under the influence of this additive the rate became proportional to the first powers of the concentrations of aromatic, acetyl nitrate and sulphuric acid. Sulphuric acid markedly catalysed the zeroth-order nitration and acetoxylation of o-xylene without affecting the kinetic form of the reaction. ... 

In the nitration and acetoxylation of o-xylene the addition of acetic acid increased the rate in proportion to its concentration, the presence of 3-0 mol 1" accelerating the rate by a factor of 30. In the presence of a substantial concentration (2-2 mol 1 ) of acetic acid the rate of reaction obeyed the following kinetic expression... 

TABLE 5.4 Yields moles %) in the nitration and acetoxylation of some derivatives of benzene at 25 °C... 

Expts. 16, //. Pure nitric acid was used. In expt. 16 the reaction was of the first order in the concentration of the aromatic, and of half-life 1-1-5 minutes (similar to that of toluene under the same conditions). In expt. 17 the sodium nitrate slowed the reaction (half-life c. 60 min). About 2 % of an acetoxylated product was formed (table 5-4). 

The fact that nitration with acetyl nitrate is sometimes accompanied by acetoxylation has been mentioned ( 5.3.3). In proposing the ion pair ACONO2H+ NOg- as the nitrating agent, Fischer, Read and Vaughan also suggested that it was responsible for the acetoxylation, which was regarded as an electrophilic substitution. 

If acetoxylation were a conventional electrophilic substitution it is hard to understand why it is not more generally observed in nitration in acetic anhydride. The acetoxylating species is supposed to be very much more selective than the nitrating species, and therefore compared with the situation in (say) toluene in which the ratio of acetoxylation to nitration is small, the introduction of activating substituents into the aromatic nucleus should lead to an increase in the importance of acetoxylation relative to nitration. This is, in fact, observed in the limited range of the alkylbenzenes, although the apparently severe steric requirement of the acetoxylation species is a complicating feature. The failure to observe acetoxylation in the reactions of compounds more reactive than 2-xylene has been attributed to the incursion of another mechan-104... 

More information has appeared concerning the nature of the side reactions, such as acetoxylation, which occur when certain methylated aromatic hydrocarbons are treated with mixtures prepared from nitric acid and acetic anhydride. Blackstock, Fischer, Richards, Vaughan and Wright have provided excellent evidence in support of a suggested ( 5.3.5) addition-elimination route towards 3,4-dimethylphenyl acetate in the reaction of o-xylene. Two intermediates were isolated, both of which gave rise to 3,4-dimethylphenyl acetate in aqueous acidic media and when subjected to vapour phase chromatography. One was positively identified, by ultraviolet, infra-red, n.m.r., and mass spectrometric studies, as the compound (l). The other was less stable and less well identified, but could be (ll). 

Tetralin shows evidence in n.m.r. spectroscopy, similar to that mentioned above, for the formation of one or more addition complexes. Tetralin (like indan) is known to undergo acetoxylation. ... 

It is noteworthy that the compounds which have been shown to undergo extensive acetoxylation or side-chain nitration, viz. those discussed above and hemimellitene and pseudocumene (table 5.4), are all substances which have an alkylated ring position activated towards electrophilic attack by other substituents. 

In MeOH, l,4-dimethoxy-2-cyclohexene (379) is obtainejl from 1,3-cydo-hexadiene[315]. Acetoxylation and the intramolecular alkoxylation took place in the synthesis of the naturally occurring tetrahydrofuran derivative 380 and is another example of the selective introduction of different nucleo-philes[316]. In intramolecular 1,4-oxyacetoxylation to form the fused tetrahy-drofurans and tetrahydropyrans 381, cis addition takes place in the presence of a catalytic amount of LiCI, whereas the trans product is obtained in its absence[317]. The stereocontrolled oxaspirocyclization proceeds to afford the Irons product 382 in the presence of Li2C03 and the cis product in the presence of LiCl[ 318,319]. 

Three oxidative reactions of benzene with Pd(OAc)2 via reactive rr-aryl-Pd complexes are known. The insertion of alkenes and elimination afford arylalk-enes. The oxidative functionalization of alkenes with aromatics is treated in Section 2.8. Two other reactions, oxidative homocoupling[324,325] and the acetoxylation[326], are treated in this section. The palladation of aromatic compounds is possible only with Pd(OAc)2. No reaction takes place with PdCl2. 

In the first step of the reaction, the acetoxylation of propylene is carried out in the gas phase, using soHd catalyst containing pahadium as the main catalyst at 160—180°C and 0.49—0.98 MPa (70—140 psi). Components from the reactor are separated into Hquid components and gas components. The Hquid components containing the product, ahyl acetate, are sent to the hydrolysis process. The gas components contain unreacted gases and CO2. After removal of CO2, the unreacted gases, are recycled to the reactor. In the second step, the hydrolysis, which is an equhibrium reaction of ahyl acetate, an acid catalyst is used. To simplify the process, a sohd acid catalyst such as ion-exchange resin is used, and the reaction is carried out at the fixed-bed Hquid phase. The reaction takes place under the mild condition of 60—80°C and ahyl alcohol is selectively produced in almost 100% yield. Acetic acid recovered from the... 

Allyl Acetate. Industrial production of aHyl acetate started only rather recendy. Nevertheless, among the aHyl compounds, its production is second to that of aHyl chloride. It is produced mostiy for manufacturing aHyl alcohol and its manufacture by acetoxylation of propylene has been described previously. The aHyl acetate obtained may be separated and purified by distillation. 

An especially interesting case of oxygen addition to quinonoid systems involves acidic treatment with acetic anhydride, which produces both addition and esterification (eq. 3). This Thiele-Winter acetoxylation has been used extensively for synthesis, stmcture proof, isolation, and purification (54). The kinetics and mechanism of acetoxylation have been described (55). Although the acetyhum ion is an electrophile, extensive studies of electronic effects show a definite relationship to nucleophilic addition chemistry (56). 

Electrophilic addition to quinones, eg, the reaction of 2-chloro-l,4-ben2oquinones with dia2onium salts, represents a marked contrast with acetoxylation in product distribution (58). Phenyldia2onium chloride (Ar = C H ) yields 8% 2,3-substitution [80632-59-3] 75% 2,5-substitution [39171-11-4] and 17% 2,6-substitution [80632-60-6]. Fory)-chlorophenyldia2onium chloride, the pattern is 28% 2,3-substitution [80632-61-7], 35%... 

Other large-volume esters are vinyl acetate [108-05-4] (VAM, 1.15 x 10 t/yr), methyl methacrylate [80-62-6] (MMA, 0.54 x 10 t/yr), and dioctyl phthalate [117-81-7] (DOP, 0.14 x 10 t/yr). VAM (see Vinyl polymers) is produced for the most part by the vapor-phase oxidative acetoxylation of ethylene. MMA (see Methacrylic polymers) and DOP (see Phthalic acids) are produced by direct esterification techniques involving methacryHc acid and phthaHc anhydride, respectively. 

Coumarin-3-carboxylic acid, 6-nitro-ethyl ester reduction, 3, 691 Coumarinic acid synthesis, 3, 685 Coumarinoisocoumarin synthesis, 3, 834 Coumarins acetoxylation, 3, 680 acylation, 3, 689 annelated... 

Possible Interference from Hydroxy and Acetoxyl Groups... 

An isolated acetoxyl function would be expected to be converted into the alkoxide of the corresponding steroidal alcohol in the course of a metal-ammonia reduction. Curiously, this conversion is not complete, even in the presence of excess metal. When a completely deacetylated product is desired, the crude reduction product is commonly hydrolyzed with alkali. This incomplete reduction of an acetoxyl function does not appear to interfere with a desired reduction elsewhere in a molecule, but the amount of metal to be consumed by the ester must be known in order to calculate the quantity of reducing agent to be used. In several cases, an isolated acetoxyl group appears to consume approximately 2 g-atoms of lithium, even though a portion of the acetate remains unreduced. Presumably, the unchanged acetate escapes reduction because of precipitation of the steroid from solution or because of conversion of the acetate function to its lithium enolate by lithium amide. 

However, suitably located hydroxyl and acetoxyl functions can assist the cisoid approach of the peracid reagent. While 4jS-acetoxycholest-5-ene gives a 9 1 ratio of the a- and jS-epoxides, the 4a-acetoxy-5-ene yields the a-epoxide exclusively. The directive effect can be used to prepare and /9-oxiranes from A -steroids as illustrated by the epoxidation of (16) and (18). 

However, this does not explain the structural requirements for the oxygen function vicinal to the nitrite ester a-ketones, ketals and hydroxyls are cleaved, but a-acetoxyls are not. 

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