Naphthalene Friedel-Crafts acylation

Anthraquinone dyes are derived from several key compounds called dye intermediates, and the methods for preparing these key intermediates can be divided into two types (/) introduction of substituent(s) onto the anthraquinone nucleus, and (2) synthesis of an anthraquinone nucleus having the desired substituents, starting from benzene or naphthalene derivatives (nucleus synthesis). The principal reactions ate nitration and sulfonation, which are very important ia preparing a-substituted anthraquiaones by electrophilic substitution. Nucleus synthesis is important for the production of P-substituted anthraquiaones such as 2-methylanthraquiQone and 2-chloroanthraquiaone. Friedel-Crafts acylation usiag aluminum chloride is appHed for this purpose. Synthesis of quinizatia (1,4-dihydroxyanthraquiQone) is also important. 

The important bluish mixing component 11.22 for whitening polyester is made by Friedel-Crafts acylation of pyrene (Scheme 11.17). This tetracyclic hydrocarbon is not unlike anthracene in its susceptibility to substitution reactions. The most stable bond arrangement in pyrene appears to be that shown as form 11.47a, which contains three benzenoid (b) rings. Canonical form 11.47b, containing only two such rings, contributes to a lesser extent (Scheme 11.18). In all monosubstitutions, pyrene is attacked initially at the 3-position, corresponding to the a-positions in anthracene or naphthalene. 

Compounds 1 and 2 were identified by FTIR and 13C-NMR. The 13C proton decoupled spectra for 1 and 2 are dominated by signals ranging from 62 to 195 ppm. The 13C chemical shift assignments were made based on comparisons with 4,4 -(hexafluoroisopropylidene)diphenol and from calculations based on substituted benzenes and naphthalenes.15 The 13C-NMR spectrum clearly showed that the Friedel-Crafts acylation of 1 by 4-fluorobenzoyl chloride yielded the 1,4-addition product exclusively. The 13C chemical shifts for 2 are listed in Table 8.1. The key structural features in the FTIR spectrum of2 include the following absorptions aromatic C-H, 3074 cnr1, ketone C=0, 1658 cm-1, aromatic ether Ar—0—Ar, 1245 cm-1, and C—F, 1175 cm-1. 

Anthraquinone itself is traditionally available from the anthracene of coal tar by oxidation, often with chromic acid or nitric acid a more modern alternative method is that of air oxidation using vanadium(V) oxide as catalyst. Anthraquinone is also produced in the reaction of benzene with benzene-1,2-dicarboxylic anhydride (6.4 phthalic anhydride) using a Lewis acid catalyst, typically aluminium chloride. This Friedel-Crafts acylation gives o-benzoylbenzoic acid (6.5) which undergoes cyclodehydration when heated in concentrated sulphuric acid (Scheme 6.2). Phthalic anhydride is readily available from naphthalene or from 1,2-dimethylbenzene (o-xylene) by catalytic air oxidation. 

Synthesis of racemic naproxene Friedel-Crafts acylation (aluminum chloride - nitrobenzene) of p-naphthol methyl ether affords 2-acetyl-6-methoxy naphthalene, which, when treated with either dimethyl sulfonium or dimethylsulfoxonium methylide, gives 2-(6-methoxynaphthalen-2-yl)propylene oxide. Treatment of the latter with boron trifluoride etherate in tetrahydrofuran gives 2-(6-methoxynaphthalen-2-yl)propionaldehyde, which is oxidized using Jones reagent (4 M chromic acid) to yield the racemic 2-(6-methoxynaphthalen-2-yl)propionic acid. 

Fluorous biphase catalysis was also applied in Friedel-Crafts acylation with Yb tris(perfluoroalkanesulfonyl)methide catalysts with acid anhydrides.59 Of the aromatics studied, activated compounds and naphthalene (95% conversion) showed satisfactory reactivity. 

Hydroboration of a variety of alkenes and terminal alkynes with catecholborane in the fluorous solvent perfluoromethylcyclohexane was performed using fluorous analogs of the Wilkinson catalyst.135 136 Recycling of a rhodium-based alkene hydrosilylation catalyst was also successful.137 Activated aromatics and naphthalene showed satisfactory reactivity in Friedel-Crafts acylation with acid anhydrides in the presence of Yb tris(perfluoroalkanesulfonyl)methide catalysts.138... 

In a third microreactor, the anion of 4-ferf-butyl l-ethyl-2-(diethox-yphosphoryl)succinate was prepared in situ using sodium ethoxide 237 (in EtOH) and the Wittig-Horner olefination with benzaldehyde 116 performed using a residence time of 47 min to afford (E)-ferf-butyl-l-ethyl-2-benzylidenesuccinate 238 in excellent selectivity (89% yield). In a fourth reactor, the acid-catalyzed (TFA 239) ferf-butyl ester deprotection was achieved using a residence time of 5 min at 34 °C and employing DCM as the reaction solvent to afford (E)-3-(ethoxycarbonyl)-4-phenylbut-3-enoic acid 246 in 82% yield. The deprotection was subsequently followed by a Friedel-Crafts acylation, using triethylamine 14 and acetic anhydride 37, to afford 4-acetoxy-naphthalene-2-carboxylic acid ethyl ester 241 in quantitative yield when conducted at 130 °C (residence time = 47 min). 

Substrates of Friedel-Crafts acylations are benzene and naphthalene, as well as their halogen, alkyl, aryl, alkoxy, or acylamino derivatives. Acceptor-substituted aromatic compounds are inert. Because Friedel-Crafts acylations introduce an acceptor into the aromatic substrate, no multiple substitutions take place. This distinguishes them from Friedel-Crafts alkylations. Free OH and NH2 groups in the aromatic compound prevent Friedel-Crafts acylations because they themselves are acylated. However, the O-acylphenols available in this way can later be rearranged with A1C1, into orf/zo-acylated isomers (Fries rearrangement). 

The commercial preparation of anthraquinone dyes begins with the synthesis of anthraquinone itself. In this regard, the three-step synthesis involves (1) the oxidation of naphthalene to phthalic anhydride, (2) Friedel-Crafts acylation of benzene to give a keto acid, and (3) cyclodehydration using H2S04. See Fig. 13.110. The preparation of 1,4-disubstituted anthraquinones utilizes the intermediates... 

The most important method for the preparation of aryl ketones is known as Friedel-Crafts acylation. The reaction is of wide scope. Reagents other than acyl halides can be used," including carboxylic acids," anhydrides, and ketenes. Oxalyl chloride has been used to give diaryl 1,2-diketones." Carboxylic esters usually give alkylation as the predominant product (see 11-11)." A-Carbamoyl p-lactams reacted with naphthalene in the presence of trifluoromethanesulfonic acid to give the keto-amide." ... 

Free-ion attack is more likely for sterically hindered R. The ion CH3CO has been detected (by IR spectroscopy) in the liquid complex between acetyl chloride and aluminum chloride, and in polar solvents, such as nitrobenzene but in nonpolar solvents, such as chloroform, only the complex and not the free ion is present." In any event, 1 equivalent of catalyst certainly remains complexed to the product at the end of the reaction. When the reaction is performed with RCO+SbFg, no catalyst is required and the free ion" " (or ion pair) is undoubtedly the attacking entity." The use of LiC104 on the metal triflate-catalyzed Friedel-Crafts acylation of methoxy-naphthalene derivatives has been examined, and the presence of the lithium salt leads to acylation in the ring containing the methoxy unit, whereas reaction occurs in the other ring in the absence of lithium salts." Note that lithium perchlorate forms a complex with acetic anhydride, which can be used for the Friedel-Crafts acetylation of activated aromatic compounds." ... 

We have seen that naphthalene undergoes nitration and halogenation chiefly at the a-position, and sulfonation and Friedel-Crafts acylation at either the a- or jS-position, depending upon conditions. Now, to what position will a second substituent attach itself, and how is the orientation influenced by the group already present ... 

Derivatives of anthracene are seldom prepared from anthracene itself, but rather by ring-closure methods. As in the case of naphthalene, the most important method of ring closure involves adaptation of Friedel-Crafts acylation. The products initially obtained are anthraquinones, which can be converted into corresponding anthracenes by reduction with zinc and alkali. This last step is seldom carried out, since the quinones are by far the more important class of compounds. 

Gunnewegh, E.A., Gopie, S. S., and van Bekkum, H. 1996. MCM-41 type molecular sieves as catalysts for the Friedel-Crafts acylation of 2-methoxy-naphthalene. /. Mol. Catal. A Chem. 106 151-158. 

A number of commercially important fragrance molecules have been synthesised by Friedel-Crafts acylation reactions in these ionic liquids. Traseolide (5-acetyl-l,l,2,6-tetramethyl-3-isopropylindane) (Scheme 5.2-24) has been made in high yield in the ionic liquid [EMIMjCl-AlCls (X = 0.67). For the acylation of naphthalene, the ionic liquid gives the highest reported selectivity for the 1-position... 

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