Anisole para selectivity

Bromodesilylation T-methoxy-l-indanones. Cyclization contrary to the normal para-selectivity of anisole derivatives can be effected by temporary use of an ort/jo-trimethylsilyl group introduced by directed orf/io-metallation (11,75). Thus the anisole derivative 1 undergoes bromodesilylation and hydrolysis to provide 2. This product undergoes cyclization to 3 in good yield on conversion to the lithio salt followed by bromine-lithium exchange (8,65-66). 

Anodic chlorination of toluene and anisole using graphite electrodes, chemically modified with a-cyclodextrin, results in higher para selectivity in comparison to chlorination with NaOCl in presence of a-cyclodextrin in solution384. Similar results are observed with a Pt electrode38. ... 

Microsolvent effects in the cyclodextrin cavity have also been observed in hypochlorite chlorination of acetophenone1029. Higher para selectivity has been observed in the bromination of acetanilide and benzanilide in presence of cyclodextrins or amylose1030 and in the anodic chlorination of anisole with cyclodextrin-modified electrode1031. 

All the catalysts tested were active in this reaction and all had very high para selectivity. In conclusion all heterogeneous catalysts can be active toward acylation of anisole with different types of acylation agent, which can be anhydrides, esters, or acids. One important point which is not always discussed in the literature is the ratio of the two reactants, which has a dramatic impact on the adsorption competition of the reactants and on the ability to desorb the formed product. 

Cyclodextrins exhibit remarkable ortho-para selectivity in the chlorination of aromatic compounds by hypochlorous acid (HOCl) [22] (Scheme 5). Chlorination takes place via formation of a covalent intermediate, a hypochlorite ester of cyclodextrin. In the chlorination of anisole by hypochlorous acid, pura-chlorination occurs almost exclusively in the presence of sufficient cyclodextrin, although in control experiments maltose had no effect on the product ratio. For example, selectivity for para-chlorination in the presence of 9.4 X 10 M a-cyclodextrin is 96%, which is much larger than that in the absence of a-cyclodextrin (60%). In the proposed mechanism, one of the secondary hydroxyl groups reacts with HOCl to form a hypochlorite ester, which attacks the sterically favorable para position of the anisole molecule included in the cyclodextrin cavity in an intracomplex reaction. The participation of one of the secondary hydroxyl groups at the C-3 position in the catalysis was shown by the fact that dodecamethyl-a-cyclodextrin, in which all the primary hydroxyl groups and all the secondary hydroxyl groups at the C-2 positions are methylated, exhibited equal or larger ortho-para specificity than native a-cyclo-... 

In all the reactions described above, CyDs promote para-selectivity. In some reactions, however, CyDs catalyze the formation of ortho-products. When anisole and pentyl chloroacetate in the presence of a-CyD (3 mM), ortho-alkylated anisole is efficiently and selectively formed (80% selectivity) [18a]. The selective reactions are ascribed to a cage effect and geometric control to the CyD cavity. 

Zeolites have been used to enhance the / r i-selectivity of chlorination reactions. For example, anisole has been chlorinated using sulfuryl chloride and ZF520 zeolite under reflux conditions [10]. A yield of 81% was achieved with a para to ortho product ratio of 74 26. Smith et al. reported complete conversion of alkylbenzenes using tertiary-butyl hypochlorite and HNaX zeolite at room temperature with para to ortho ratios of greater than 90 10 [11]. Molecular chlorine in the liquid phase with KL zeolite as the catalyst has been reported to give excellent para selectivity and good yields for deactivated benzenes [12]. 

Friedel-Crafts Acylation. Acetylation and benzoylation of aromatics have been performed in ionic liquids such as [BMIM]-[BF4] by using Cu(OTf)2 as catalyst. Under these conditions, benzoylation of activated aromatics such as anisole (eq 16) is reported to be quantitative and exhibits high para-selectivity (orthapara = 4 96). 

With toluene as substrate formylation proceeded in a high yield (99%) with respect to aldehyde formation and with good para-selectivity (90%) in a reaction time of only 1 hour. The reaction was carried out on phenol under the same reaction conditions. Surprisingly, the reactivity of phenol proved to be much lower than that of toluene and a reaction time of more than 4 hours was required to obtain acceptable yields, albeit with reduced para-selectivity. When the reaction was extended to anisole, only small differences compared to phenol were observed within the first hour of the reaction, but at extended reaction times phenol proved to give better conversions. The results indicate that the reaction is sustained for a longer time with phenol than with anisole. 

Chloro-aluminate ionic liquids promote the carbonylation of alkylated aromatic compounds, but fails in the case of oxygenated aromatics. Aldehyde yields of formylation in the acidified neutral ionic liquids were generally similar compared to reactions conducted in HF as solvent/catalyst (cf Table 2.2). The increase in aldehyde yields with the use of extended alkyl chain lengths of the cationic part of the melt, may be due to improved CO solubility. HF/BFs-acidified neutral ionic liquids showed both increases in para-selectivity compared to HF as solvent and catalyst. Formylation of anisole and toluene, but not of phenol in the neutral ionic liquids resulted in increased secondary product formation in comparison with hydrogen fluoride used as solvent/catalyst. This difference in behaviour is not understood at present, but suggests that phenol is a good substrate for formylation in this medium, particularly with the development of a system catalytic with respect to HF/BF3 in mind. 

Smith et al. (1998) have reported selective para acetylation of anisole, phenetole, and diphenyl ether with carboxylic anhydrides at 100 °C, in the presence of catalytic quantities of zeolites H-beta. The zeolite can be recovered and recycled to give essentially the same yield as that given by fresh zeolite. 

The catalytic activity of Mg/Al/O sample in m-cresol gas-phase methylation is summarized in Figure 1, where the conversion of m-cresol, and the selectivity to the products are reported as a function of the reaction temperature. Products were 3-methylanisole (3-MA, the product of O-methylation), 2,3-dimethylphenol and 2,5-dimethylphenol (2,3-DMP and 2,5-DMP, the products of ortho-C-methylation), 3,4-dimethylphenol (3,4-DMP, the product of para-C-methylation), and poly-C-methylated compounds. Other by-products which formed in minor amounts were dimethylanisoles, toluene, benzene and anisole (not reported in the Figure). 

Unsubstituted cycloamyloses have been used to catalyze a number of reactions in addition to acyl group transfer. Brass and Bender (8) showed that cycloamyloses promoted phenol release from diphenyl and bis(p-nitro-phenyl) carbonates and from diphenyl and bis(m-nitrophenyl)methyl phos-phonates. Breslow and Campbell (10,11) showed that the reaction of anisole with HOCL in aqueous solution is catalyzed by cyclohexaamylose and cycloheptaamylose. Anisole is bound by the cyclodextrins and is chlorinated exclusively in the para position while bound. Cycloheptaamylose has been used to promote regiospecific alkylation followed by the highly selective oxidation shown in reaction (3) (95). In addition cycloheptaamylose effec-... 

As reported in the literature, the acylation of aromatic hydrocarbons can be carried out by using zeolites as catalysts and carboxylic acids or acyl chlorides as acylating agents. Thus toluene can be acylated by carboxylic acids in the liquid phase in the presence of cation exchanged Y-zeolites (ref. 1). The acylation of phenol or phenol derivatives is also reported. The acylation of anisole by carboxylic acids and acyl chlorides was obtained in the presence of various zeolites in the liquid phase (ref. 2). The acylation of phenol by acetic acid was also carried out with silicalite (ref. 3) or HZSM5 (ref. 4). The para isomer has been generally favoured except in the latter case in which ortho-hydroxyacetophenone was obtained preferentially. One possible explanation for the high ortho-selectivity in the case of the acylation of phenol by acetic acid is that phenylacetate could be an intermediate from which ortho-hydroxyacetophenone would be formed intramolecularly. 

However, the frontier orbital picture based on the free arene does not account for nearly exclusive meta selectivity in addition to [(anisole)Cr(CO)3] LUMO for anisole shows essentially the same pattern as for toluene.98-100 With a strong resonance electron donor the traditional electronic picture (deactivation of the ortho and para positions) is sufficient to account for the observed meta selectivity. In this case the balance of charge control and orbital control is pushed toward charge control by strong polarization. The same argument applies to the aniline and fluotobenzene complexes. 

The products formed in these reactions are very sensitive to the functionality on the carbenoid. A study of Schechter and coworkers132 using 2-diazo-1,3-indandione (152) nicely illustrates this point. The resulting carbenoid would be expected to be more electrophilic than the one generated from alkyl diazoacetate and consequently ihodium(II) acetate could be used as catalyst. The alkylation products (153) were formed in high yields without any evidence of cycloheptatrienes (Scheme 33). As can be seen in the case for anisole, the reaction was much more selective than the rhodium(II)-catalyzed decomposition of ethyl diazoacetate (Scheme 31), resulting in the exclusive formation of the para product. Application of this alkylation process to the synthesis of a novel p-quinodimethane has been reported.133 Similar alkylation products were formed when dimethyl diazomalonate was decomposed in the presence of aromatic systems, but as these earlier studies134 were carried out either photochemically or by copper catalysis, side reactions also occurred, as can be seen in the reaction with toluene (equation 36). 

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