Graphite acylation

Use of graphite-supported methodology has been reported for three types of reaction - the Friedel-Crafts acylation [15, 16, 27, 66], the acylative cleavage of ethers [15, 16], and the ketodecarboxylation of carboxylic diacids [67, 68], either with conventional heating (GS/A) or MW irradiation (GS/MW coupling) these are discussed below. First, however, we describe the analysis of two commercial graphites of different purity which are used for these experiments. 

In 1994 our preliminary results revealed, surprisingly, that FC acylation could be realized in the presence of graphite A, under solvent-free conditions, under the ac-... 

Comparative attempts at graphite-supported acylation of anisole, toluene, and naphthalene using classical heating afforded interesting results [66]. With nonvolatile reactants the yields were almost identical with those obtained under the action of MW. In contrast, if at least one reactant was volatile (MeCOCl, PrCOCl) or sublim-... 

Tab. 7.8 Acylation of aromatic compounds in the presence of a small amount of graphite and under the action of MW irradiation [27, 66].

The catalytic effect of graphite A thus depends on iron impurities, e. g. Fe304, and probably also on iron sulfides or sulfates, because sulfur is also present in this graphite, and all these iron compounds are known catalysts of FC acylation [69, 73, 74], In this respect, it seems that FeCl3 could be the true catalyst generated in situ by the reaction of the different iron compounds with acid chloride and hydrogen chloride. In the... 

Comparison with previous FC acylations, the above processes are clean, without aqueous workup, and therefore without effluents ( green chemistry ). The graphite is, moreover, inexpensive and can be safety stored or discarded. Its activity is, however, limited to activated aromatic compounds. 

The process which seems to have the most possibilities for a scale-up development is that using a low amount of graphite, for which the desorption treatment can be totally suppressed in a continuous flow system. We recently proposed the use of such a process to perform FC acylations under the action of MW with FeCl3 as catalyst [76 d]. The replacement of FeCl3 by a graphite bed is quite conceivable in the same continuous flow apparatus. 

Heterocyclic derivatives of a range of metals other than lithium have received considerable attention, especially as precursors for coupling reactions. These derivatives can be prepared either directly from halo compounds or from the lithio compounds. Thus, direct formation of the pyrrolylzinc compounds can be effected under very mild conditions by treatment of an iodide with a zincsilver couple deposited on graphite. The zinc reagents are formed in excellent yields and can be converted into acylated or allylated products (Scheme 140). For further discussion on this theme, see Section 3.3.3.8.8. 

In retrospect, it is ironic to it that when I met Ernst Schumacher in 1969 (he was then Professor at the University of Bern in Switzerland) we did not talk about the experiments he did at Zurich in the same building where I was at that time. Instead, his interest focussed on our work on borazine transition metal compounds and we discussed in some detail whether it would be possible to incorporate metal atoms like chromium or molybdenum between the layers of hexagonal boron nitride (BN) in a similar way as it can be done with graphite. In the course of these discussions I did not mention that, after I had moved to Zurich, we had begun to investigate the reactivity of nickelocene towards both nucleophilic and electrophilic substrates. The reason was that we were still at the beginning, and while we had been able to prepare a series of monocyclopentadienyl nickel complexes from Ni(C5H5)2 and Lewis bases, our attempts to obtain alkyl- or acyl-substituted nickelocenes by the Friedel-Crafts reaction failed. 

Quantitative conversion of 1-adamantanecarbonyl chloride to 1-adamantanecarbox-aldehyde has been accomplished by reduction of the acyl halide at carbon and mercury in MeCN containing TEAP [227]. Lozano and Barba [228] reduced 2-chloro-2-phenylacetyl chloride at mercury in methylene chloride containing TEACl and obtained derivatives of pyran-2-one and pyran-4-one. In subsequent work [229,230], these authors investigated the reduction of 2-bromo-2,2-diphenylacetyl bromide at graphite in methylene chloride containing TEABr and in the presence of inorganic sulfur compounds in the first study, a new sulfurated heterocyclic product was obtained ... 

Acylations. Catalyzed by graphite the Friedel-Crafts acylation as well as the transformation of ethers to esters by acyl halides in refluxing 1,2-dichloroethane are realized. Although aliphatic chlorides are inferior to aromatic halides this method is quite general as shown by the synthesis of benzoates (e.g., allyl benzoate from allyl benzyl ether and methyl benzoates from methyl f-butyl ether). 

Reaction of indoloquinazoline and anthranilic acids, adsorbed on graphite, led to 61 Reaction of aldehydes, 2-aminopyrimidine and alkyl isocyanide afforded 62. A route to 63 was described by reaction of A-acyl imidates with imidazolidine ketene aminals ... 

Consequently, a lot of research has been carried out in this area in order to find convenient catalysts, i.e. those able to activate the acylating reagent while giving labile complexes with ketones, in particular in hot conditions. Ferric chloride is the most common catalyst when the reaction is achieved in this manner (refs. 7, 8). With this same view, Friedel-Crafts acylation in the presence of small quantities of catalysts (for example FeCl3), is strongly activated by microwave irradiation, in particular when the catalyst is on a graphite substrate (ref. 9). 

Graphite has also been described as a surprising acylating catalyst whereas carbon black is inactive [31] again no information was given about the exact composition and metal impurity content, and the results should be considered with caution. 

Table 4.24 Aromatic acylation with acyl halides catalyzed by graphite...

To overcome tbe problem of tbe bigb amount of graphite utilized and mainly to avoid tbe use of tbe expensive and pollutant acyl balides and benzene, graphite can be coupled with para-toluenesulfonic acid and utilized to activate the more ecocompatible carboxylic acids toward electrophilic acylation. i With this catalyst, not only a solvent-free process can be developed but also high yields with not activated aromatic substrates and with unactivated carboxylic acids (i.e., para-nitrobenzoic acid) can be obtained (Table 4.25). 

Interestingly, in the presence of graphite or para-toluenesulfonic acid alone, no acylated products are isolated. The effect of the solvent is detrimental since only traces of the products are detected when the reactions are carried out in methylene chloride or chloroform. It must be underlined that graphite can be reused after simple washing with ethyl acetate and water, but the para-toluenesulfonic acid, which is not adsorbed on the graphite during the reaction, must be added again for the successive runs. 

Table 4.25 Aromatic acylation with carboxylic acids in the presence of graphite-para-toluenesulfonic acid mixture...

Kodomari, M., Suzuki, Y., and Yoshida, K. 1997. Graphite as an effective catalyst for Friedel-Crafts acylation. Chem. Commun. 1567-1568. 

Sarvari, M. H. and Sharghi, H. 2005. Solvent-free catalytic Friedel-Crafts acylation of aromatic compounds with carboxylic acids by using a novel heterogeneous catalyst system p-toluenesulfonic acid/graphite. Helv. Chim. Acta 88 2282-2287. 

Graphite combined with methanesulfonic acid represents an effective catalyst for the acylation of phenols and naphthols, wifh carboxylic acids giving a good yield of ortho-hydroxy aryl ketones (Table 5.4). The reactions seem to be faster with activated aromatic carboxylic acids. It must be emphasized that, in the absence of graphite, in the model reaction between mefa-cresol and BAC, the product is isolated in lower yield (20% versus 81%). 

Table 5.4 Promotion of acylation of phenols with carboxylic acids by graphite-methanesulfonic acid...

Sharghi, H., Hosseini-Sarvari, M., and Eskandari, R. 2006. Direct acylation of phenol derivatives in a mixture of graphite and methanesulfonic acid. Synthesis 2047-2052. 

---