Acylation of thiophene

Sulfonated styrene—divinylbensene cross-linked polymers have been appHed in many of the previously mentioned reactions and also in the acylation of thiophene with acetic anhydride and acetyl chloride (209). Resins of this type (Dowex 50, Amherljte IR-112, and Permutit Q) are particularly effective catalysts in the alkylation of phenols with olefins (such as propylene, isobutylene, diisobutylene), alkyl haUdes, and alcohols (210) (see Ion exchange). Superacids. 

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. 

A very convenient method for the direct acylation of thiophenes with the free acids has been introduced by Yuryev. It consists of refluxing the acid with SiCb in benzene, and without isolation of the formed tetraacyloxysilanes, Si(OCOR)4, reacting them with SnCb and thiophene. >2 The yields are between 57 and 94%. The lower... 

Additional acylation studies were also reported (24), (26). In the first case it is claimed that acylation of thiophene is achieved by means of HC104 and acetic anhydride affording a 65 % yield of 2-acetylthiophene. In the second paper Levine and coworkers reported that while 2,5-dimethylthiophene could be readily acetylated, 2,5-dichlorothiophene acetylated sluggishly. This is, however, readily explained, since the presence of chlorine atoms on the thiophene ring decreased its reactivity in electrophilic substitution reactions. In the case of methyl substitution, however, the 3 and 4 positions of the ring are activated toward electrophilic substitution by the inductive and hyperconjugative effects. Thus 2,5-dimethylthiophene was successfully acylated by the boron fluoride etherate method in high yield with three aliphatic anhydrides. 

The acylation of thiophenes has been reviewed (86HC(44/3)309). The best catalyst for the Friedel-Crafts acylation of thiophene, using free carboxylic acids, appears to be 2-(trifhioromethylsulfonyloxy)pyridine (84) in conjunction with TFA. 2-Acylthiophene is formed in quantitative yield, without any evidence of the thiophene dimerizing. The reaction might be mediated by the mixed anhydride (85) (Scheme 15) (88BCJ455) (cf. (84CHEC-(4)74l)). 

Intramolecular acylation of thiophenes has been thoroughly examined and shown to provide a reasonable route to substituted cycloalkanones on desulfurization of the bicyclic products (53BSF62, 73BSF343). A variety of five-, six- and seven-membered ring systems have been constructed, e.g. (285) — (287). 

Hi) Carboxylic acids and derivatives. The haloform reaction on thienyl methyl ketones leads to thiophenecarboxylic acids, which can be treated with Raney nickel to produce the open-chain acids. This method has been used for the five-carbon homologation of carboxylic acids and to produce dicarboxylic acids (Scheme 51). Long-chain carboxylic acids may also be prepared by using dicarboxylic acid derivatives for the acylation of thiophenes (Scheme 52). In the synthesis of Queen substance, the precursor (213) has been generated by Raney nickel desulfurization of the appropriate thiophene-2-acetic acid derivative (79T329). 

Finiels, A., Calmettes, A., Geneste, P. and Moreau, P. Kinetic study of the acylation of thiophene with acyl chlorides in liquid phase over HY zeolites, Stud. Surf. Sci. Catal., 1993, 78, 595-600. 

As part of a program on replacing AICI3 with ecologically acceptable catalysts, the acylation of thiophene with 4-fluorobenzoyl chloride in the presence of commercial acid-treated clays has been investigated. Complete conversion could be achieved, leading to almost complete formation of the 2-acylthiophene with only traces of the 3-isomer (Equation 13) . 

Stable 2H-thiophenium ions formed on acylation of thiophene and its homologs with aluminum chloride (due to hydrogen chloride originating during the reaction) essentially lower the yields of ketones. The formation of such cr-complexes, a-C-protonation products, does not take place on preparation of ketones under the usual conditions of acylation in thiophene series, namely, in the presence of tin tetrachloride with... 

The first three reactions are all electrophilic substitution a bromination of a pyrrole, the nitration quinoline, and a Friedel-Crafts acylation of thiophene. Bromination occurs on the pyrrole at only remaining site. Nitration of quinoline occurs on the benzene rather than the quinoline r-fi (actually giving a mixture of 5- and 8-nitroquinolines, but don t worry if you didn t see t- Mi p. 1174), and the acylation would occur next to sulfur. 

Butyroyl chloride was utilized in the acylation of thiophene in the presence of zeolite Y with the aim of studying the nature and effect of the catalytic acid sites. The reaction is performed in chlorobenzene at... 

The same catalyst gives excellent synthetic results in the acylation of thiophene with different acyl chlorides. For example, 2-butyroylthio-phene is easily and quantitatively produced from the acylation of thiophene with butyroyl chloride at 100°C after 7 h. Higher homologs lead to identical results (Scheme 4.9). 

Kinetic study of the acylation of thiophene with acyl chlorides in liquid phase over HY zeolites... 

Acylation reactions of thiophene have been also investigated under heterogeneous conditions a montmorillonite clay and silica-alumina [9] and Nafion-H [10] have been shown to be efficient catalysts of the acylation of thiophene with acetyl chloride. 

Our interest in the use of zeolites as shape selective catalysts in liquid-phase acylation [12] and alkylation [13] reactions of aromatic derivatives led us to consider their ability to catalyse the acylation of thiophene in relatively mild conditions, compared with the previous results [11]. 

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