Acetic anhydride toluene acylation

Amino-5-methylamino-l,2,4-thiadiazole similarly gives a 3-toluene-p-sulfonamido111,122 (237) and a monobenzamido derivative (for structure, see ref. 122) an excess of the appropriate reagent yields non-acidic di- and tri-substitution products, the latter probably of structure 239. With acetic anhydride, however, acylation terminates with the formation of the 3-monoacyl derivative.111,122 Similar observations areon record concerning 3-amino-5-anilino-1,2,4-thiadiazole86 the only anomalous observation is the ability of this compound to form di- and tri-acetyl derivatives.58... 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

Lipase-catalyzed enantioselective transesterification of 0-substituted-l,2-diols is another practical route for the synthesis of P-blockers. Lipase PS suspended in toluene catalyzes the transesterification of (63) with vinyl acetate to give the (5)-ester in 43% yield and >98% ee (78). The desired product, optically pure (R)-ttitylglycidol, is then easily obtained by treating the ester with alcohoHc alkaU. Moreover, Pseudomonas Hpase catalyzes the acylation of oxazohdinone (64) with acetic anhydride in very good yield and selectivity (74). PPL-catalyzed transesterification of a number of /n j -norbomene derivatives proceeds in about 30% yield and 92% ee (79,80). 

Among the wide variety of organic reactions in which zeolites have been employed as catalysts, may be emphasized the transformations of aromatic hydrocarbons of importance in petrochemistry, and in the synthesis of intermediates for pharmaceutical or fragrance products.5 In particular, Friede 1-Crafts acylation and alkylation over zeolites have been widely used for the synthesis of fine chemicals.6 Insights into the mechanism of aromatic acylation over zeolites have been disclosed.7 The production of ethylbenzene from benzene and ethylene, catalyzed by HZSM-5 zeolite and developed by the Mobil-Badger Company, was the first commercialized industrial process for aromatic alkylation over zeolites.8 Other typical examples of zeolite-mediated Friedel-Crafts reactions are the regioselective formation of p-xylene by alkylation of toluene with methanol over HZSM-5,9 or the regioselective p-acylation of toluene with acetic anhydride over HBEA zeolites.10 In both transformations, the p-isomers are obtained in nearly quantitative yield. 

For the first example, we chose to acylate olefin alcohol la. This was readily accomplished using acetic anhydride and 4-DMAP in pyridine to provide ester 17. Methylenation, using Takai s (10) protocol, yielded the acyclic enol ether 18 which was subsequently cyclized with 15 mol % of the Schrock catalyst 6 in hot toluene to afford the glycal 19 in good yield. Hydroboration and oxidative work-up led to the methyl-C-glycoside 20 (Scheme 4). With this proof of principle in hand, we then set out to prepare a number of additional examples as shown in Table 1 (11). 

Because a carboxylic anhydride and BF3 constitute a mild Friedel-Crafts acylating system, it is not surprising that nucleophilic aromatic substrates such as toluene, mesi-tylene, and anisole have been acetoacetylated [61]. The expected 1,3-diketones are formed when a sufficient excess of acetic anhydride is present in the reaction mixtures. The process is illustrated with anisole in Eq. (33) [61]. 

For acylations with propionyl and phenylacetyl chlorides, see Ref. 71JCS(C)706. 4-Amino-5-phenyltriazole, refluxed with ethyl acetoacetate in toluene, gave 4-acetoacetamido-5-phenyltriazole (7 hr, 67%), which hot acetic anhydride converted to the 3-acetyl derivative. However, the reaction of 4-aminotriazole-5-carboxamide with cold acetoacetic ester gave a IV-vinyl (and not a iV-acyl) derivative (see Section III,B) [73JCS(P1)943]. 

Catalytic acylation of electron-rich aromatics is achieved with a combination of InCls and silver perchlorate (Scheme 8.114) [157]. Acetic anhydride, acetyl chloride and isopropenyl acetate serve as satisfactory acyl donors. By using an InCl3-impreg-nated Si-MCM-41 catalyst at low concentration, acylation of aromatic compounds (benzene, toluene, p-xylene, mesitylene, anisole, naphthalene, methylnaphfhalene, and methoxynaphfhalene) by acyl chlorides (benzoyl chloride, phenylacetyl chloride, propionyl chloride, or butyryl chloride) can be accomplished rapidly (3 h) at 80 °C in high yield, even in the presence of moisture in the aromatic substrate or solvent (dichloroethane) (Scheme 8.115) [158], In(OTf) j is an efficient catalyst in the sulfonylation of both activated and deactivated aromatic compounds (Scheme 8.116) [159]. 

Anisole can be acylated with acetic anhydride in 99% yield (6.12). Yttterbium triflate can also be used. The yields are low when there is no activating group in the ring. The rate is accelerated by the addition of lithium perchlorate.56 Acylation of alcohols works well with 1 mole% of scandium triflate as a catalyst (6.13).57 The less toxic toluene has also been used as the solvent in such acylations. The... 

Differential thermal analysis measurement at atmospheric pressure. b Prepared by acylation of 12a with acetic anhydride in refluxing toluene (24h) and recrystallization from benzene. 

Good synthetic results have been achieved in the acylation of ferrocene with acetic anhydride (AAN) in EtMeimCl-AlClg/toluene mixture. The monoacetylated product can be obtained in 80%-96% yield, ft is significant that no acetylation of toluene is observed under these conditions. 

Botella, R, Corma, A., Lopez-Nieto, J. M., Valencia, S., and Jacquot, R. 2000. Acylation of toluene with acetic anhydride over Beta zeolites influence of reaction conditions and physicochemical properties of the catalyst. /. Catal. 195 161-168. 

In contrast to anisole, the acylation of toluene with HPA is far less efficient than that with H-Beta. These results can be explained by the well-known strong affinity of bulk HPA towards polar oxygenates, which would lead to the preferential adsorption of acetic anhydride on HPA, blocking access for toluene to the catalyst surface. It appears that the hydrophobic zeolites with high Si/Al ratios less strongly differentiate the adsorption than the hydrophilic HPA and, therefore, are more suitable catalysts for the acylation of nonpolar aromatics like toluene. 

The hydrothermally prepared HBEA zeolites, using amorphous silica as the silicon source, give a very selective synthesis of 4-methylacetophenone 11 in the acylation of toluene with acetic anhydride. In particular, it is shown that HBEA(32) gives product 11 with 80% yield and 98% selectivity (Scheme 3.6) [31]. 

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