Anhydrides addition-elimination

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). 

In 1970, it was disclosed that it is possible to achieve the conversion of dimethylformamide cyclic acetals, prepared in one step from vicinal diols, into alkenes through thermolysis in the presence of acetic anhydride." In the context of 31, this two-step process performs admirably and furnishes the desired trans alkene 33 in an overall yield of 40 % from 29. In the event, when diol 31 is heated in the presence of V, V-dimethylforrnamide dimethyl acetal, cyclic dimethylformamide acetal 32 forms. When this substance is heated further in the presence of acetic anhydride, an elimination reaction takes place to give trans olefin 33. Although the mechanism for the elimination step was not established, it was demonstrated in the original report that acetic acid, yV, V-dimethylacetamide, and carbon dioxide are produced in addition to the alkene product."... 

Isoquinoline 2-oxide was converted by bromine in acetic anhydride in the presence of sodium acetate into the 4-bromo 2-oxide, presumably via an addition-elimination process (84MI2). Metallic derivatives have been used occasionally to prepare bromoisoquinolines, as in the formaton of 79, a process accompanied by ring-opening [87JCS(PI)1865]. 

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

In contrast, oxime ethers and esters are usually stable in solution but the E/Z isomerization can be induced by acids " or by irradiation ". Recently, Narasaka and colleagues"" "" studied the equilibration-isomerization of (E)-O-acyl oximes 239 in the presence of an acid in a nucleophilic solvent (equation 71). Isomerization probably proceeds via protonation of the oxime nitrogen followed by addition-elimination of a nucleophilic solvent until the equilibrium of E and Z isomers is achieved. The isomerization of the more labile 0-acyloximes occurs either by an Sjv2 substitution at the oxime nitrogen with acids and/or by acyl exchange through the formation of a mixed anhydride and the free oxime. 

The Grohe-Heitzer sequence (Scheme 4.2) begins with acylation of malonate derivative 37 with benzoyl chloride 36 to give malonate 38 (Mitscher, 2005). Condensation of the malonate with an ortho-ester in the presence of a dehydrating agent such as acetic anhydride affords enol ether 39. The enol ether then undergoes an addition-elimination... 

Thioamide formation benzodiazepinone, 505 heteiodiazepinone, 621 phosphorus pentasulf ide, 323, 600 Thioazole formation, nitrile addition, 301 Thiocarbamate formation, 588 phenol, 95 rearrangement, 517 Thioenol ether formation, 185, 517 addition-elimination, 554 Thioester formation, mixed anhydride, 184 Thioether formation, 241, 300, 413, 416 alkylation, 586, 588 aromatic displacement, 416 Thiohydantoin formation, 293 Thiol interchange, benzothiazole formation, 422... 

Tetraphenyltellurophene fails to undergo Diels-Alder addition with maleic anhydride even when heated at 220 °C for 21 h. Tetraphenyltellurophene 1,1-dibromide, however, on heating with maleic anhydride undergoes elimination of tellurium to produce tetraphenyl-furan and/or the dibenzopentalene derivatives (76) and (77) (61JA4406). 

Next, the carboxylate anion participates in an addition-elimination reaction with isobutyl chloroformate. Elimination of a chloride anion results in formation of intermediate A. These reactions are generally facilitated by the introduction of an amine base such as triethylamine (not shown in this problem). The mechanism is illustrated below using arrow pushing, and the illustrated product belongs to a class of compounds known as mixed carbonic anhydrides. 

Mixed carbonic anhydrides are a form of activated esters that can react with amines to form amides. The addition-elimination mechanism, illustrated below using arrow pushing, involves addition of an amine followed by an elimination step driven by the release of carbon dioxide. 

Pyridine /V-oxide is unreactive toward iron-catalyzed bromination at 110°C (55JA2902), but silver sulfate-catalyzed bromination in sulfuric acid at 200°C gives a 10% yield of 2- and 4-bromination in the ratio 1 2 (6ITL32). With bromine in oleum the main product is 3-bromopyridine /V-oxide (60%) together with the 2,5-dibromo (—35%), and 2,3- and 3,4-dibromo compounds (—5%) (62T227). Presumably the N-oxide function is here complexed with sulfur trioxide, which causes deactivation and 3-orientation. Bromination in acetic anhydride also gives 3-substitution (35%) an addition-elimination mechanism has been proposed (65JPJ62). 

Key Mechanism 21-1 Addition-Elimination Mechanism of Nucleophilic Acyl Substitution 998 Mechanism 21-2 Conversion of an Acid Chloride to an Anhydride 1001... 

Michels and Hayes102 investigated the nitration of a furan and used a mixture of acetic anhydride and nitric acid. The reaction takes place by the addition-elimination mechanism quoted above. They accomplished the nitration in the presence of weak bases, and were able to isolate a crystalline intermediate ... 

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