Methoxynaphthalene acylation anhydrides

Another patent apphcation (28) describes the use of zeolite/TUD-1 with optionally a metal function for a variety of reactions. In an example, as-synthesized MCM-22 / TUD-1 was tested for acylation of 2-methoxynaphthalene with acetic anhydride to 2-acetyl-6-methoxynaphthalene at 240°C. After reaction for six hours, conversion of 2-methoxynaphthalene reached 56% with 100% selectivity to 2-acetyl-6-methoxynaphthalene. Other zeolite catalysts were similarly tested, but none were nearly as effective. 

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... 

Figure 3.2 Reaction scheme of the acylation of 2-methoxynaphthalene (2-MN) with acetic anhydride (AA) over zeolites. Most activated and activated positions for the electrophilic substitution are indicated by and, respectively...

Aromatic ketones are important intermediates in the production of fine chemicals and pharmaceuticals1,2. Thus, the anti-rheumatic Naproxen is produced by the Friedel-Crafts acetylation of 2-methoxynaphthalene into 2-acetyl-6-methoxynaphthalene and subsequent Willgerodt-Kindler reaction. Commercial acylation processes involve over-stoechiometric amounts of metal chlorides (e g. AICI3) as catalysts and acid chlorides as acylating agents, which results in a substantial formation of by-products and in corrosion problems. This is why the substitution of these corrosive catalysts by solid acid catalysts and of acid chlorides by anhydrides or acids is particularly desirable. 

The reaction was carried out at 100°C with sulpholane as solvent and acetic anhydride as acylating agent [9]. The results conversion of 2MN and the ratio of the two ketone products, l-acetyl-2-methoxynaphthalene (lAC) over 2-acetyl-6-methoxy-naphthalene (2AC), are given in Table 2. The selectivity for the two products was better than 95% in all cases. 

Acylation of 2-methoxynaphthalene with acetic anhydride was carried out using different solid acid catalysts such as zeolites, acid activated clays, ion exchange resins and sulphated zirconia. The products of the reaction are precursors of many organic and pharmaceutical intermediates. For example, the para isomer of the reaction product, 6-methoxy-2-naphthalene-a-methyl ketone is useful as a raw material for the manufacture of well-known anti-inflammatory dru called naproxen. The reaction products were isolated and confirmed by their melting points, H-NMR, gas chromatography, etc. 

The acylation of 2-methoxynaphthalene (yarayara) with acetic anhydride was studied systematically by using Amberlyst-15 and Indion-130, sulphated zirconia, Filtrol-24, K-10-montmorillonite clay, aluminium pillared clay(Al-PILC), HPA, HPA/KIO, H-ZSM-5, Y,... 

P. A. 2006. Acylation of 2-methoxynaphthalene with acetic anhydride over silica-embedded triflate catalysts. Appl. Catal. A Gen. 306 159-164. 

In another example, as-synthesized swollen MCM-22 / TUD-1 was tested (31) for acylation of 2-methoxynaphthalene with acetic anhydride to 2-acetyl-6-... 

Acylation of 1,4-dimethoxynaphthalene with acetic anhydride (1.2 equiv) and aluminum chloride (2.2 equiv) in ethylene dichloride (60 C, 3 h) gives two products, 6-acetyl-1,4-dimethoxynaphthalene (30%) and l-hydroxy-2-acetyl-4-methoxynaphthalene (50%). Suggest a rationalization for the formation of these two products and in particular for the differing site of substitution in the two products. 

Fe - and Zn -exchanged clays promote the acylation of 2-methoxynaphthalene with acetic anhydride affording the kinetically favored l-acetyl-2-methoxynaphthalene in 82% yield [69-71]. 

Also obtained by acylation of 2-methoxynaphthalene with propionic anhydride in nitrobenzene in the presence of zeolite-beta catalysts [7840]. 

Friedel-Crafts Reactions. Aluminum trifluoromethanesulfonate has been used for the Friedel-Crafts alkylation reaction of toluene with isopropyl and tert-butyl chlorides (eq 1), and for the acylation of benzene and toluene with acetyl and benzoyl chlorides in low to moderate yields. Intramolecular Friedel-Crafts acylation of an aromatic compound with Meldrum s acid has also been reported using catalytic amounts of Al(OTf)3. Acylation of 2-methoxynaphthalene with acetic anhydride has been reported using Al(OTf)3 and lithium perchlorate as an additive to afford the corresponding 6-acetylated adduct in 83% yield. Effective acylation of arenes with carboxylic acids has also been disclosed using polystyrene-supported Al(OTf)3. ... 

Sb(0S02CF3)3 has been reported as Lewis catalyst for reactions requiring traces of water. Benzoylation of toluene, acylation of m-xylene, and sulfonylation of toluene were examples demonstrating its role in Friedel-Crafts reactions [26]. Also, catalytic amount of Sb(OTf)3 catalyzed the reaction of 2-methoxynaphthalene with acetic anhydride in nitromethane-lithium perchlorate to afford 2-acetyl-6-methoxynaphthalene, a well-known intermediate for the synthesis of naproxen, in a high yield [27]. 

These catalysts have been tested in a variety of reactions such as acylation of alcohols and alkylation of phenols and naphthols [71,72,96,100,101,108]. The encapsulated triflate derivatives, and particularly the immobilized Lewis acid r rr-butyldimethylsilyltri-fluoromethanesulfonate, are very active catalysts in acylation of 2-methoxynaphthalene with acetic anhydride. In solvent-free conditions, the TOF is much higher than the values reported in literature for other heterogeneous catalysts. Moreover, leaching can be completely avoided when the solvent is omitted. The major product was in all cases the 1-acetylated methoxynaphthalene the isomerization to the 6-isomer was negligible even at high conversions. 

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