Friedel-Crafts acetylation

Conjugated dienes, upon complexation with metal carbonyl complexes, are activated for Friedel-Crafts acylation reaction at the akyhc position. Such reactions are increasingly being used in the stereoselective synthesis of acylated dienes. Friedel-Crafts acetylation of... 

Although in general azoles do not undergo Friedel-Crafts type alkylation or acylation, several isolated reactions of this general type are known. 3-Phenylsydnone (120) undergoes Friedel-Crafts acetylation and Vilsmeier formylation at the 4-position, and the 5-alkylation of thiazoles by carbonium ions is known. 

In the reactions of 2,5-disubstituted thiophenes elimination of an a-substituent occurs to a much greater extent than in the benzene series. The Friedel-Crafts acetylation of 5-bromo-2-ethylthiophene in the presence of SnCE gives 2-ethyl-5-acetyIthiophene. Elimination of an a-bromine occurs also in the chloromethylation of 2,5-di-bromothiophene, leading to a mixture of 2-bromo-5-chloromethyIthio-phene and 2,5-dibromo-3-chloromethyIthiophene. Bromine atoms at both the and -position are exchanged for chlorine in the... 

Synthesis of the prototype begins with Friedel Crafts acetylation of salicylamide ( ). Bromination of the ketone (25) followed by displacement with amine gives the corresponding ami noketone ( ). Catalytic hydrogenation to the ami noalcohol completes the synthesis of labetolol (24). The presence of two chiral centers at remote positions leads to the two diastereomers being obtained in essentially equal amounts. 

Both Friedel-Crafts acetylation and Vilsmeier formylation of the 2,3-dihydrooxazole 5 occur at C-5, indicating that the A-acyliminium ion is more stable than the oxonium ion17. This is corroborated by ab initio calculations, which show that 3-formyl-2,5-dihydro-3-oxazolium 7 is ca. 46 kJ mol 1 more stable than 3-formyl-2,4-dihydro-l-oxazolium 817. 

Scheme 3 Proposed mechanism of the Friedel-Crafts acetylation in the presence of MCI3...

Dimethylarsacymantrene (71) undergoes Friedel-Crafts acetylation at the /3 position to give adduct 110.26 By analogy to the heteroferrocene series, it is presumbed that the a position would be more reactive however, no a-unsubstituted arsacymantrenes have been reported. For comparison, 3,4-dimethylphosphacymantrene (111) is clearly acylated at the a position. See Scheme 15. 

Methyl 5-vinylsalicylate was prepared as shown in Scheme II (3). Friedel-Crafts acetylation of methyl salicylate gave the 5-acetyl derivative in 80% yield. Blocking of the phenol followed by NaBH reduction then provided methyl 5-(1-hydroxyethyl)acetyl-salicylate in an overall yield of 70%. The hydroxyethyl compound was dehydrated over KHSO at 225°C/0.2 mm, and the... 

Compound 102 is used as the building block for the syntheses of PNU-86093 and its analogues, as described in Scheme 21. Namely, the Friedel-Crafts acetylation reaction of 102 under acetic anhydride, methanesulfonic acid, and methanesulfonyl anhydride [51,65] affords compound 103 (PNU-... 

Friedel-Crafts acetylation of 64 gives a monoacetyl derivative (85%) originally formulated as 8-acetyl-1,2,3,4-tetrahydrodibenzothio-phene. Subsequent work - revealed that it was in fact the... 

Friedel-Crafts acetylation of 4-methyldibenzothiophene yields 2-acetyl-4-methyldibenzothiophene (33%), which readily undergoes the Mannich reaction. ... 

Methyl 2-(2 -acetyl-3 -benzofuranyl)acetate (121), available by Friedel-Crafts acetylation of methyl 2-(3 -benzofuranyl)acetate (120, Scheme 29), on treatment with boiling methanolic sodium methoxide affords 2,4-dibenzo-furandiol (122). ... 

C17H24O, Mr 244.38, mp 35 °C, is a synthetic musk fragrance. It is prepared by Friedel-Crafts acetylation of 1,1,2,3,3,5-hexamethylindane, which can be obtained as a 70 30 mixture with l,l,3,5-tetramethyl-3-ethylindane by reacting a,p-dimethyl-styrene with amylenes or 2-methyl-2-butanol in a mixture of acetic acid and concentrated sulfuric acid [155] ... 

C14H18N2O5, Mr 294.31, mp 137 °C, does not occur in nature. It forms yellowish crystals with a sweet, very persistent, slightly animal musk odor. Musk ketone is prepared by Friedel Crafts acetylation of l,3-dimethyl-5-tert-butylbenzene, and nitration of the resulting 2,6-dimethyl-4-/cr/-butylacetophenone with nitric acid. 

In agreement with MO calculations (V-acylation of 5H- dibenz[6,/]azepine alters considerably the pattern of electrophilic substitution. In the N-unsubstituted heterocycle the sites of electrophilic substitution are at C-2 and C-8 i.e. ortho and para to the free NH see Section 5.16.3.9.1). However, as predicted theoretically, IV-acylation deactivates the car-bocyclic nuclei towards substitution via mesomers of structure (32). As a result Friedel-Crafts acetylation furnishes the 5,10-diacetyl derivative (108). Electrophilic bromination (Br2/CHC13), unlike the free radical process (see Section 5.16.3.7), yields the 10,11-dibromo compound. In contrast, nitration of the (V-acetyl derivative at low temperature affords only the 3-nitro isomer (74CRV101). 

A report on the Friedel-Crafts acetylation of 3-methyl-4//-thiopyran (3)4 should be considered with caution because of lack of a sufficient structure proof for 3. 

Their utility has been demonstrated in various Friedel-Crafts reactions,44-47 halogen addition,48 49 electrophilic nitration of aromatics,50 and various hydrogenation processes51-53 including the Ru-catalyzed hydrogenation of C02 to /V,/V-dipropyl formamide in supercritical C02 under biphasic conditions 54 The use of in situ IR spectroscopy allowed Horvath and coworkers to demonstrate that the same substrate-catalyst and product-catalyst complexes are produced in Friedel-Crafts acetylation of benzene in ionic liquids as in CH2C12 55... 

Electrophiles attack xanthene at C-2 and sometimes also at C-7 when conditions are sufficiently vigorous. Nitric acid simultaneously oxidizes xanthene to the xanthone and thus gives 2-nitroxanthone. Friedel-Crafts acetylation of xanthene gives either 2-acetyl- or 2,7-diacetylxanthene according to the temperature (0 or 18 °C) and the proportion of acetyl chloride (74BSF2963). 

Friedel—Crafts acetylation can be achieved, but the introduction of one acetyl group deactivates the remaining chelate rings so that mixtures of mono-, di- and tri-acetyl products are formed in the case of chiomium(III) and cobalt(III) complexes, but only mono- and di-acetyl products from rhodium(III) acetylacetonate. 

Alkoxybenzo[6]thiophenes undergo electrophilic substitution in the 2-position. Thus, 6-ethoxybenzo[6]thiophene affords its 2-bromo, 2-formyl, and 2-acetyl derivatives on bromination, Vilsmeier-Haack formylation, and Friedel-Crafts acetylation, respectively,424 and 6-methoxybenzo[6]thiophene undergoes Friedel-Crafts reaction with /3-carbomethoxypropionyl chloride in the 2-position.618... 

Dimethoxy- and 5,6-methylenedioxybenzo[6]thiophene undergo bromination, Vilsmeier-Haack formylation, and Friedel-Crafts acetylation in the 2-position (see Section VI, A).189 With nitric acid, however, 5,6-methylenedioxybenzo[6]thiophene affords an unidentified mononitro derivative, which is not the 2-nitro compound.548... 

Fe(cyclooctatetraene)(CO)3] reacts under Friedel-Crafts acetylation conditions (acetyl chloride/AlCb), but only low yields of the substituted product (24) are formed the major product being the bicyclic cation (25) (equation 12).36-38... 

The formylation of hexadeuteriobenzene, C6D6, with HCOF-BF3 shows a kinetic hydrogen isotope effect of ku/kn = 2.68, based on comparison of the reactivity of C6H6/CH3C6H5 and CfiDg/CHjCfiHs432 This isotope effect is similar to that observed in Friedel-Crafts acetylation and propanoylation reactions, and it indicates that the proton elimination step is at least partially rate-determining. The low substrate... 

Dihydroxyacetophenone (6) (cognate preparation in Expt 6.107), which cannot be prepared by a Friedel-Crafts acetylation of hydroquinone, is obtained in good yield when hydroquinone diacetate (5) is heated in the presence of 3.3 mol of aluminium chloride. 

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