Anisole benzoylation with benzoyl chloride

Ethers are unaffected by sodium and by acetyl (or benzoyl) chloride. Both the purely aliphatic ethers e.g., di-n-butyl ether (C4H, )30 and the mixed aliphatic - aromatic ethers (e.g., anisole C3HSOCH3) are encountered in Solubility Group V the purely aromatic ethers e.g., diphenyl ether (C,Hj)20 are generally insoluble in concentrated sulphuric acid and are found in Solubility Group VI. The purely aliphatic ethers are very inert and their final identification may, of necessity, depend upon their physical properties (b.p., density and/or refractive index). Ethers do, however, suffer fission when heated with excess of 67 per cent, hydriodic acid, but the reaction is generally only of value for the characterisation of symmetrical ethers (R = R ) ... 

Amorphous and mesostructured Zr02 solid catalysts impregnated with various amounts of triflic acid were tested in the acylation of biphenyl356,357 and toluene358 (with benzoyl chloride and para-toluyl chloride, respectively, nitrobenzene solvent, 170°C and 130°C). All catalysts exhibited lower activity when compared with neat triflic acid. The mesoporous catalysts, however, showed complete selectivity in the formation of para-benzoylbiphenyl. A triflic acid-silica catalyst, in turn, prepared using an aminopropyl-modified silica, showed good characteristics in the solvent-less acetylation of anisole and 2-methoxynaphthalene with acetic anhydride.359,360 The activity of 1,1,2,2-tetrafluoroethanesulfonic acid, either neat or embedded in silica, was found to be similar to that of triflic acid in the acetylation of anisole.196... 

Several metal triflate salts have been tested in the Friedel-Crafts acylation of anisole with benzoyl chloride in [C4Ciim][BF4]. At a reaction temperature of 80°C and catalyst loadings of 10 mol%, all salts led to 100% conversion with reaction rates decreasing in the order Cu(OTf)2 > Zn(OTf)2 > Sn(OTf)2 Sc(OTf)3, see Scheme 9.22.[92]... 

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]. 

Table 14.5 Benzoylation of anisole with benzoyl chloride catalyzed with several zeolites.

Table 14.5 shows the results obtained for several zeolites in the reaction of benzoylation of anisole with benzoyl chloride. 

Diarylketones are also the important fine chemical intermediates, which could be prepared by the acylation of aromatic hydrocarbon with benzoyl chloride and benzoic anhydride. The ionic liquids have also been used to catalyze the synthesis of diarylke-tone. Earle et al. [105] have reported the benzoylation of benzene, derivants of benzene (toluene, anisole, isobutyl benzene, phenyl chloride and fluoride) to synthesize the diarylketone by use of chloroindate (III) ionic liquids as the green dual catalysts and solvents. As a result, good yields (75-96%) were obtained under proper conditions with the ionic liquids as the clean reaction medium and recyclable catalysts. 

An example is as follows. After protection as a silyl ether, amidation of benzyl A-(5,6-0-isopropylidene-4-hydroxycyclohex-2-enyl)carbamate 229 (prepared from 3-bromo-lS,2S-0-isopropylidenecyclohexa-3,5-diene) with (6-bromo-3,4-methylenedioxy)benzoyl chloride gave the protected N-benzyloxycarbonyl-A-(cyclohex-2-enyl)benzamide 230. A modified Heck reaction of 230 in anisole produced the protected lycoricidine 231 in 27% yield (two steps) by A-detosylation. Acid treatment of 231 provided (-H)-lycoricidine (204) in 85% yield (Scheme 22). 

The same catalyst (10% mol) can be utilized in the benzoylation of anisole by benzoyl chloride (BC), showing yield improvement when performed in combination with microwave irradiation. The BC conversion is 95% (with ortho/para isomer ratio 0.06) after 1 min irradiation at 165°C and 300 W power. The reaction can be applied to different activated arenes, giving products in high yields and showing the characteristics of an economical energy-saving process able to perform clean reactions in reduced time. A further advantage is the avoidance of the solvent since the aromatic substrate can replace it. 

The preparation and use of indium trichloride, gallium trichloride, and zinc chloride supported on MCM-41 as Lewis acids in the Friedel-Crafts acylation of aromatics with acyl chlorides was investigated. The support itself shows no catalytic activity in the benzoylation of benzene with BC, whereas the highest activity is showed by the supported indium trichloride. The order for acylation activity of the supported metal chloride (indium trichloride > gallium trichloride zinc chloride) is quite similar to that of the redox potential of the metals [E , +/, (-0.34 V) > E°Ga /Ga ( 0.53 V) > E 2n +/zn ( 0.74 V)] and confirms a possible relationship between the redox potential and the catalytic activity of the supported metal chloride. The reaction can be efficiently applied to a variety of aromatic compounds, including toluene, para-xylene, mesitylene, anisole, and 2-MN (70%-90% yield), confirming the moisture insensitivity of the catalyst. ... 

Benzoylation of anisole with BC at the para-position is performed in the presence of a catalytic amount of iron(III) oxide (85% yield) lower yields of 4-halobenzophenones are achieved with the weakly deactivated chlorobenzene (33%), bromobenzene (31%), and iodobenzene (30%). However, taking into account the possible leaching of active iron trichloride produced by the reaction of iron(III) oxide with hydrogen chloride, the contribution of the homogeneous iron-based Lewis acid form is strongly suspected. 

Zinc oxide, an inexpensive and commercially available inorganic solid, can be utilized as an efficient catalyst in the Friedel-Crafts acylation of activated and unactivated aromatic compounds with acyl chlorides at room temperature for 5 to 120 min (Table 4.14). Acylation is claimed to occur exclusively at the para-position of the monosubstituted aromatic compounds. The catalyst can be recovered and reused, after washing with methylene chloride, for at least two further cycles, showing quite similar high yield (-90%) in the model benzoylation of anisole. Mechanistically, it seems that zinc chloride can be the true catalyst, generated in situ by the reaction of zinc oxide with hydrogen chloride. 

Yadav, G. D., Asthana, N. S., and Kamble, V. S. 2003. Cesium-substituted dodecatungstophosphoric acid on K-10 clay for benzoylation of anisole with benzoyl chloride. /. Catal. 217 88-99. 

Friedel-Crafts acylation of anisole with benzoyl chloride (2 moles) by their addition together to a solution of anhydrous (5 mol%) cobait ll) chloride in dry methyl cyanide afforded a 72% yield of 4-methoxybenzophenone (ref. 126). 

Izumi et al. pioneered the use of heteropoly acids as catalysts for aromatic acylation. Silica-supported acids H4[SiWi204o] and H3[PWi204o] were found to effectively catalyse the acylation of p-xylene with benzoyl chloride. Cs2.5Ho.5[PWi204o] showed high efficiency in the acylation of activated arenes, such as p-xylene, anisole, mesitylene, etc., by acetic and benzoic anhydrides and acyl chlorides. This catalyst provided higher yields of acylated arenes than the parent acid H3[PWi204o], the latter being partly soluble in the reaction mixture. ... 

Preparation by demethylation of l,3-di-(p-methoxy-benzoyl)- benzene (SM) with hydrobromic acid (d = 1.49) in refluxing acetic acid for 6 h (68%) [1449] or for 10 h [1450]. SM was obtained by Friedel-Crafts acylation of anisole with isophthaloyl chloride [1450]. 

Also obtained by reaction of benzoyl chloride with anisole [1497]. 

D. Baudry-Barbier studied the catalytic properties of Sc, La and Nd modified KIO clays in Friedel-Crafts acylations of anisole with benzoyl chloride for yielding 4-methoxybenzophenone, and found La modified KIO clay exhibited the best catalytic activity for acylations of anisole. In comparison with the acid catalyzed reactions using liquid acids, the solid acid catalyzed process was non-polluting and also the final work-up didn t require any aqueous treatment, which exhibited wide prospect for the clean synthesis of building block and fine chemicals [195]. 

Microwave heating was applied for the liquid-phase acylation of anisole by acetic anhydride or benzoyl chloride at 80°C, with the reaction rate increasing dramatically compared to a traditional heating [181]. In addition, a significantly shorter reaction time compared to the conventional heating was observed. 

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