Acylation Using Other Catalysts

In the acylation of 2-methoxynaphthalene, the isomer formed almost exclusively is l-acetyl-2-methoxynaphthalene and no, or very little, 6-acetyl-2-meth-oxynaphthalene is formed. The one-step acylation of 2-methoxynaphthalene in the 6 position remains a challenge and is of interest because 6-acetyl-2-methoxynaphthalene is a potential intermediate for the synthesis of naproxen, an important anti-inflammatory drug. 

As already mentioned, thiophene has also been acetylated with a variety of heterogeneous catalysts such as montmorillonite clay [28] and Nafion-H [29]. 

Interesting reactivity has recently been found in the use of Nafion/silica composite material [30]. Nafion resins are active in the acylation of anisole with acetyl chloride, but entrapping highly dispersed nanosized Nafion particles in a silica matrix leads to a much more active catalyst, as indicated in Table 5. 

Substrate Nafion catalyst yield (%) Nafion/silica composite yield (%) 

Extension of the scope of the this reaction by use of Nafion/silica composite resin shows that these catalysts can be active in the acylation of xylenes yet have low activity toward toluene (Table 6). 

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Acylation. To achieve acylation of thiophenes, acid anhydrides with phosphoric acid, iodine, or other catalysts have been widely used. Acid chlorides with AlCl, SnCl, ZnCl2, and BF also give 2-thienylketones. AH reactions give between 0.5 and 2.0% of the 3-isomer. There has been much striving to find catalyst systems that minimize the 3-isomer content attempting to meet to customer specifications. The standard procedure for formylation is via the Vil smeier-H a ack reaction, using phosphoms o xycbl o ri de / /V, / V- dim e tb yl fo rm a m i de (POCl /DMF) or /V-m ethyl form an i1 i de. 

With this purpose, several different types of solid acid catalysts have been investigated for the acylation of aromatics, but the best performances have been obtained with medium-pore and large-pore zeolites (3-9). In general, however, the use of acylating agents other then halides, e.g., anhydrides or acids, is limited to the transformation of aromatic substrates highly activated towards electrophilic substitution. In a previous work (10), we investigated the benzoylation of resorcinol (1,3-dihydroxybenzene), catalyzed by acid clays. It was found that the reaction mechanism consists of the direct 0-benzoylation with formation of resorcinol monobenzoate, while no primary formation of the product of C-benzoylation (2,4-dihydroxybenzophenone) occurred. The latter product formed exclusively by... 

Boron trifluoride complexes are also often applied. BF3 when used with acyl fluorides showed in some cases distinct differences compared to other catalyst-reagent combinations. For example, acylation of 2-methylnaphthalene with isoBuCOF and BF3 gives high yield (83%) of the 6-substituted isomer in contrast to AICI3 (30%).40 A similar example is shown here ... 

The preparation of the first unsaturated azlactone was reported in 1883 by Plochl/40 who condensed benzaldehyde with hippuric acid in presence of acetic anhydride. This approach was later used by Erlenmeyer/41 who extended the procedure to include other aldehydes and also established the usefulness of azlactones as intermediates in the synthesis of DHAs. The method involves the condensation of an A-acylglydne 4 with aldehydes and ketones in the presence of acetic anhydride and anhydrous sodium acetate (Scheme 2)J41 t5l Other catalysts such as copper(II) acetate/46 lead acetate/47,48 potassium carbonate/49 or potassium hydrogen carbonate 50 have also been used. The reaction proceeds via formation of an azlactone 5, which then condenses with the appropriate aldehyde or ketone to give unsaturated azlactone 6. Reaction of 6 with a nucleophile such as OH, OR, or NHR leads to the corresponding A-acyl-DHA derivatives 7. Reaction with the sodium salt of an amino acid gives a DHA containing dipeptide acid. 51 ... 

The acylal (4) can also be used to carry out reactions with nascent dimethylketene formed in situ. It is stable to t-butanol at the reflux temperature but with potassium carbonate present to ciitaly/,c cleavage it reacts smoothly to form /-butyl isobutyrate It reacts with an amine without other catalyst at room temperature to give an isohutyramide. In the presence of an alkali carbonate or the salt of a carboxylic acid, it converti an acid Into Its anhydride, probably via a mixed anhydride. With... 

When examining in detail these results it appeared very difficult for us to build upon these experimental results as the reaction condition differ drastically from one paper to the other. This prompted us to reinvestigate the scope and limitation of the Friedel-Crafts acylation using heterogeneous solid as catalysts in trying as much as we could to rationalized the observed effects. 

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