Ortho-acylated product

As expected, the para-acylated ketone 3 is the major reaction product, with only minor yields of the ortho-acylated product formed. Reaction is very rapid and complete conversions are obtained. Catalyst TOP numbers are >19000h under these conditions. Enolisation and further reaction with the anhydride results in formation of the vinyl ester. Minor amounts of diacile and side products are formed. Similar performances are observed with both supported and nonsupported ST A (at equivalent ST A loading in reactor). Use of nonsupported ST A resulted in agglomeration and deposition of the material onto the reactor wall, whereas the silica supported material could be readily removed by filtration. 

The first atropo-enantioselective total synthesis of a phenylanthraquinone natural product (Af)-knipholone was reported by G. Bringmann et al. In the late stages of the synthesis, an acetyl group had to be introduced under mild conditions. The advanced substituted anthraquinone intermediate was first deprotected with TiCU and then acylated with AC2O in the presence of TiCU. A spontaneous Fries-rearrangement took place to afford the ortho-acylated product in high yield. The natural product was obtained by a mono O-demethylation at C6 with AIBrs. 

Phenol esters of a,(3-unsaturated carboxylic acids have an interesting reactivity due to the synthetic utility of the resulting hydroxychalcones (Scheme 19). This aspect will be illustrated in Section IV. However, from the basic point of view, it is worth mentioning that the cis or trans configuration of the olefinic part of the acyl moiety can have a marked influence on the photochemical reactivity of the ester. When para-methoxyphenyl fumarates are irradiated, the normal ortho-rearranged products are obtained. By contrast, irradiation of para-me-thoxyphenyl maleates does not lead to rearrangement. Instead, cyclization products are obtained (Scheme 20). 

The rearrangement of aryl and naphthyl acetates has been reported to be catalyzed by Bi(0Tf)3xH20 (Scheme 9) [68, 69]. As previously reported, only ortho-Fries products (l-hydroxy-2-acylaromatics) were produced from substrates for which ortho acylation was possible. In the case of 2,6-dimethoxyphenyl acetate, only the 3,5-dimethoxy-2-hydroxy acetophenone was produced, indicating that in this case the mechanism involves an intermolecular acyl-group transfer. As in other reactions, the nature of the true catalyst is still unclear since triflic acid also catalyzes this reaction. 

The use of activated anthranihc acid derivatives facUitates the preparation of the amides in those cases where the amines are either umeactive or difficult to obtain. Thus, reaction of (87-1) with phosgene gives the reactive the isatoic anhydride (89-1). Condensation of that with ortho-toluidine leads to the acylation product (89-2) formed with a simultaneous loss of carbon dioxide. This is then converted to the quinazolone (89-3) by heating with acetic anhydride. Reaction with sodium borohydride in the presence of aluminum chloride selectively reduces the double bond to yield the diuretic agent metolazone (89-4) [99]. 

The acylation of alkylbenzenes with benzoyl chloride and a catalytic amount of per-fluorobutanesulfonic acid affords the corresponding alkyl-substituted benzophe-nones with unusually high amounts of ortho isomeric products (up to 30%) 38... 

Intramolecular Friedel-Crafits acylation can be used to make rings. Use Spartan-Build to build and minimize the ortho, meta, and para acylation products from the following reaction. Which product has the lowest strain energy How do the highen energy isomers reveal the presence of strain ... 

The Fries reaction can also be metal-promoted to afford, under the proper reaction conditions, good yields of specific ortho acyl migration products. For instance, o-bromophenyl pivaloate (248) has been treated at —95 °C with s-butyllithium to afford o-hydroxypivalophenone (249) in 76% yield (equation 178) . Similarly, benzoate 250 gave o-hydroxyketone 251 in 82% yield by treatment with n-butyllithium (equation 179) °. 

The production of aromatic hydroxyketones can also be performed by the Fries rearrangement in this case, the mode of para-acylation is probably different from that of ortho-acylation. Indeed, the ortho-isomer is a primary product, whereas the para-isomer seems to be a secondary product. Of course, other methods for... 

Unmodified BEA zeolite, on the other hand, shows the highest activity in the acylation of phenol wifh benzoic anhydride. Phenyl benzoate (PB) is the main product (61% yield), accompanied by C-acylated products (35%), with an interesting para-selectivity (ortho/para = 0.48). When the reaction time is increased from 4 to 20 h, an increase in para-hydroxy-benzophenone yield (from 11% to 23%) fogefher wifh a decrease in PB yield (from 79% to 64%) is observed however, a small increase in the orf/zo-hydroxybenzophenone yield (from 9% to 10%) cannof be avoided. The acfivify of the catalyst, together with its selectivity, does not distinctly decrease when the catalyst is used from fresh to firsf recycle. 

The acylation of anisole with C2 - C12 acids was carried out under the same conditions as that of toluene, except a shorter reaction time (5 h). The acylated anisole formed as the major product para/ortho = 59 1 - 96 1 and no meta isomers) together with esterification products - methyl esters of carboxylic acids and phenol. No phenyl esters formed. The selectivity to esters increases from acetic to dodecanoic acid, reaching 40% for the latter. The acylation of anisole, in contrast to that of toluene, is most efficient with C2 - C6 acids, giving a 62 - 65% yield of acylated products and only 2 - 6% of methyl esters. 

Some other transition metal carbonyl compounds were also investigated instead of Ru3(CO)i2, such as Os3(CO)i2, Rh4(CO)i2, Re2(CO)io, but none of them showed any activity in this reaction. The mechanism behind this reaction was most likely the fact that a coordinatively unsaturated metal center of the trinuclear cluster is attacked and coordinated by pyridine, and subsequent ortho-metalation gives the key intermediate. Olefin insertion into a linear and branched alkyl species, followed by CO coordination and insertion, produces the acyl species, which reacts further to the acylated product by reductive elimination. 

The acylation of arenes with alcohols has been shown to be possible using a palladium chloride catalyst in the presence of f-butylhydroperoxide. In 2-arylpyridines, substitution is directed to the ortho-position and, after initial paUadation, the formation of intermediate (59) is likely before reductive elimination yields the acylated product. The regioselective acetoxylation of indoles, at the 3-position, has been achieved using the palladium-catalysed reaction with phenyliodonium acetate. 3-Acyl indoles may also be prepared using acetyl chlorides with zirconium tetrachloride as a Lewis acid catalyst. 

Metal triflates that can be easily prepared from metal halides and triflic acid at -78°C [14] show several unique properties compared with the corresponding metal halides. The use of bismuth(III) triflate allows for acylation of both activated and deactivated aromatic compounds with anhydrides and acyl chlorides [15]. Thus, the acylation of deactivated aromatics such as trifluoromethoxyben-zene, fluorobenzene, and chlorobenzene can be achieved in high yields with benzoyl chloride in the presence of bismuth(III) triflate (10% mol) without solvent. The />ara-acylation product is the most abundant in all cases (trifluoromethoxybenzene 87% yield, ortho.para 4 96 fluorobenzene 86% yield, orthoipara 0 100 chlorobenzene 89% yield, ortho para 13 87). 

The rearrangement is found to be of intramolecular nature. The radical pair remains in the solvent cage and their recombination in the cage affords the acyl migration products, while hydrogen abstraction by the phenoxy radical from the solvent leads to the formation of phenol as by-product. When the reaction of phenyl acetate was carried out with deuterated phenol in methanol, the major products were ortho- and para-hydroxy acetophenones and phenol. Only trace amounts of crossover products were obtained [42]. The presence of methoxy substiment at meta- and para-positions increases the yield of ortho-Vries product [43]. For example, 39 gives 40. 

Acylated Corticoids. The corticoid side-chain of (30) was converted iato the cycHc ortho ester (96) by reaction with a lower alkyl ortho ester RC(OR )2 iu benzene solution ia the presence of i ra-toluenesulfonic acid (88). Acid hydrolysis of the product at room temperature led to the formation of the 17-monoesters (97) ia nearly quantitative yield. The 17-monoesters (97) underwent acyl migration to the 21-monoesters (98) on careful heating with. In this way, prednisolone 17a,21-methylorthovalerate was converted quantitatively iato prednisolone 17-valerate, which is a very active antiinflammatory agent (89). The iatermediate ortho esters also are active. Thus, 17a,21-(l -methoxy)-pentyhdenedioxy-l,4-pregnadiene-liP-ol-3,20-dione [(96), R = CH3, R = C Hg] is at least 70 times more potent than prednisolone (89). The above conversions... 

N-Substituted amides can be prepared by direct attack of isocyanates on aromatic rings.The R group may be alkyl or aryl, but if the latter, dimers and trimers are also obtained. Isothiocyanates similarly give thioamides. The reaction has been carried out intramolecularly both with aralkyl isothiocyanates and acyl isothiocyanates.In the latter case, the product is easily hydrolyzable to a dicarboxylic acid this is a way of putting a carboxyl group on a ring ortho to one already there (34 is... 

Regioselectivity in Friedel-Crafts acylations can be quite sensitive to the reaction solvent and other procedural variables.45 In general, para attack predominates for alkylbenzenes.46 The percentage of ortho attack increases with the electrophilicity of the acylium ion, and as much as 50% ortho product is observed with the formylium and... 

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