Friedel Crafts with iron chloride

Friedel-Crafts catalyst. Iron serves as a satisfactory catalyst for the reaction of phenolic ethers with f-butyi chloride.5... 

Chiral diene—iron tricarbonyl complexes were acylated using aluminum chloride to give acylated diene—iron complexes with high enantiomeric purity (>96% ee). For example, /ra/ j -piperjdene—iron tricarbonyl reacted with acyl haUdes under Friedel-Crafts conditions to give l-acyl-l,3-pentadiene—iron tricarbonyl complex without any racemization. These complexes can be converted to a variety of enantiomericaHy pure tertiary alcohols (180). 

The chlorination of benzene can theoretically produce 12 different chlorobenzenes. With the exception of 1,3-dichlorobenzene, 1,3,5-trichlorobenzene, and 1,2,3,5-tetrachlorobenzene, all of the compounds are produced readily by chlorinating benzene in the presence of a Friedel-Crafts catalyst (see Friedel-CRAFTS reactions). The usual catalyst is ferric chloride either as such or generated in situ by exposing a large surface of iron to the Hquid being chlorinated. With the exception of hexachlorobenzene, each compound can be further chlorinated therefore, the finished product is always a mixture of chlorobenzenes. Refined products are obtained by distillation and crystallization. 

The Friedel-Crafts acylation reaction has also been performed in iron(III) chloride ionic liquids, by Seddon and co-workers [96]. An example is the acetylation of benzene (Scheme 5.1-66). Ionic liquids of the type [EMIM]Cl/FeCl3 (0.50 < X(FeCl3) < 0.62) are good acylation catalysts, with the added benefit that the ketone product of the reaction can be separated from the ionic liquid by solvent extraction, provided that X(FeCl3) is in the range 0.51-0.55. 

The ability of iron(III) chloride genuinely to catalyze Friedel-Crafts acylation reactions has also been recognized by Holderich and co-workers [97]. By immobilizing the ionic liquid [BMIM]Cl/FeCl3 on a solid support, Holderich was able to acetylate mesitylene, anisole, and m-xylene with acetyl chloride in excellent yield. The performance of the iron-based ionic liquid was then compared with that of the corresponding chlorostannate(II) and chloroaluminate(III) ionic liquids. The results are given in Scheme 5.1-67 and Table 5.1-5. As can be seen, the iron catalyst gave superior results to the aluminium- or tin-based catalysts. The reactions were also carried out in the gas phase at between 200 and 300 °C. The acetylation reac-... 

The chloride is usually (but not always) stabilised in storage by addition of aqueous alkali or anhydrous amines as acid acceptors. A 270 kg batch which was not stabilised polymerised violently when charged into a reactor. Contact of the chloride (slightly hydrolysed and acidic) with rust led to formation of ferric chloride which catalysed an intermolecular Friedel-Craft reaction to form polybenzyls with evolution of further hydrogen chloride. Contact of unstabilised benzyl chloride with aluminium, iron or rust should be avoided to obviate the risk of polycondensation. See Benzyl bromide Molecular sieve... 

Proton acids can be used as catalysts when the reagent is a carboxylic acid. The mixed carboxylic sulfonic anhydrides RCOOSO2CF3 are extremely reactive acylating agents and can smoothly acylate benzene without a catalyst.265 With active substrates (e.g., aryl ethers, fused-ring systems, thiophenes), Friedel-Crafts acylation can be carried out with very small amounts of catalyst, often just a trace, or even sometimes with no catalyst at all. Ferric chloride, iodine, zinc chloride, and iron are the most common catalysts when the reactions is carried out in this manner.266... 

Acetylation and formylation are classical reactions in porphyrin chemistry. H. Fischer s synthesis of hemin, for which he was awarded the 1930 Nobel prize, required treatment of deuterohemin (49) with acetic anhydride (or acetyl chloride) in the presence of tin(IV) chloride as a Friedel-Crafts catalyst the product, 3,8-diacetyldeuterohemin-IX (50), was obtained in high yield. Fischer also accomplished formylation of iron porphyrins using dichloromethyl methyl ether and a Friedel-Crafts catalyst (B-37MI30700). Both of Fischer s examples resulted in peripheral substitution of unsubstituted iron porphyrins. However,... 

Pentamethylcyclopentadienyl) ( j5-cyclopentadienyl) iron has been prepared by the alkylation of ferrocene under Friedel-Crafts conditions with methylchloride,1 and also by reaction of ferrous chloride or FeBr2 DME (DME = 1,2-dimethoxyethane) with equimolar quantities of pentamethyl-cyclopentadienyl sodium and cyclopentadienyl lithium.2,3... 

Weak Base Anion Exchangers. Both styrenic and acrylic copolymers can be converted to weak base anion-exchange resins, but different synthetic routes are necessary. Styrene—DVB copolymers are chloromethylated and aminated in a two-step process. Chloromethyl groups are attached to the aromatic rings (5) by reaction of chloromethyl methyl ether [107-30-2], CH3OCH2Cl, with the copolymer in the presence of a Friedel-Crafts catalyst such as aluminum chloride [7446-70-0], A1C13, iron(III) chloride [7705-08-0]9 FeCl3, or zinc chloride [7646-85-7], ZnC. ... 

The former is prepared (Expt 6.15) by the reaction of cyclopentadiene with iron(n) chloride in the presence of diethylamine. Iron(n) chloride is prepared in situ from iron(m) chloride in tetrahydrofuran by reduction with iron metal. This preparation is one of the simplest for ferrocene, although not of general application for substituted ferrocenes. The acetylation of ferrocene in a Friedel-Crafts manner to yield the monoacetyl derivative is described in Expt 6.122. 

Friedel-Crafts sulfonylation of benzene and its derivatives can also be carried out using iron(III) chloride-based ionic liquids, as was shown by Samant and coworkers [23]. For example, the synthesis of diphenyl sulfone, an important intermediate for the anti-leprosy drug Dapsone, was achieved in 78% yield catalyzed by 1-butyl-3-methylimidazolium chloride combined with FeCl3 (Scheme 6.7). 

Benzyl acetate was prepared by addition of benzyl chloride (containing 0.6% pyridine as stabiliser) to preformed sodium acetate at 70°, followed by heating at 115°, then finally up to 135°C to complete the reaction. On one occasion, gas began to be evolved at the end of the dehydration phase, and the reaction accelerated to a violent explosion, rupturing the 25 mm thick cast iron vessel. This was attributed to presence of insufficient pyridine to maintain basicity, dissolution of iron by the acidic mixture, and catalysis by ferric chloride of a Friedel-Craft type polycondensation reaction to polybenzyls, with evolution of hydrogen chloride, which at 130°C would produce an overpressure approaching 100 bar. Previously the chloride had been supplied in steel drums containing 10% sodium carbonate or 3% sodium hydroxide solutions as... 

An explosion occurred during the preparation of iron(III) chloride from iron powder and chlorine gas in a chlorinated pyridine solvent. This was attributed to formation of iron(II) chloride, its interaction with the solvent to give iron(III) chloride, then reduction of the latter by iron to iron(II) chloride. The exotherm and increasing evolution of hydrogen chloride caused the reactor to fail [1], Another account of what seems to be the same incident attributes the mnaway to Friedel Crafts type polymerisation of trichloromethylpyridines largely present in the reactor [2]. 

Friedel-Crafts alkylation occurs when biphenyl is treated with tert-butyl chloride and iron (III) chloride (a Lewis acid catalyst) the product of monosubstitution is p-ferf-butylbiphenyl. All the positions of the ring that bears the tert-butyl group are sterically hindered, so the second alkylation step introduces a tert-butyl group at the para position of the second ring. 

Benzylation of toluene with benzyl chloride, which is a typical example of Friedel-Crafts alkylation, is known to be catalyzed by Lewis-type superacids such as A1C13 and BF3. This type of catalyst has been mostly used for the Friedel-Crafts reaction, which is one of the most studied of organic reactions. This reaction was performed over several metal oxides and sulfates, and iron sulfates showed an unexpected effectiveness for the reaction (102-104). The catalytic activities of FeS04 and Fe2(S04)3 for the reaction were examined in detail the activities were remarkably dependent on calcination temperature, the maximum activity being observed with calcination at 700°C (105-107). Catalytic actions analogous to the above case were also observed with other Friedel-Crafts reactions, the benzoyl-ation of toluene with benzoyl chloride (108), the isopropylation of toluene with isopropyl halides (109), and the polycondensation of benzyl chloride UIO). 

Reaction of Complex III with acetyl chloride and aluminum chloride under typical Friedel-Crafts conditions affords acetylcyclobutadiene-iron tricarbonyl (VII) in high yields. The corresponding benzoyl derivative is similarly prepared with benzoyl chloride. Formylation with AT-methyl-formanilide and POCI3 produces cyclobutadienecarboxaldehyde-iron tricarbonyl (VIII), while chloromethylation with formaldehyde and HCl affords the chloromethyl derivative (IX). 

For the preparation of unsymmetrical ferrocenes, two ways by which only mono-substituted derivatives are produced have been suggested. One route starts from iron tetracarbonyl and a substituted cyclopenta-diene the other from monocyclopentadienyl iron dicarbonyl bromide, which on treatment with a substituted cyclopentadienyl lithium is finally converted into the corresponding mono-substituted ferrocene. Experience shows the first method to be more suitable for the preparation of aryl, and the latter method for the preparation of alkyl, derivatives (57). Corresponding work already carried out on substitution in Ru(C5H6)2 and Os CsH5)2 has also been fruitful. It is found that in the Friedel-Crafts reaction with acetyl or benzoyl chloride there is a distinct predominance of mono- over disubstitution as the atomic weight of the central atom increases (47, 72). 

The Friedel-Crafts synthesis involves the union of a relatively active compound, like a halide, with a relatively stable hydrocarbon in the presence of an anhydrous halide of aluminum, iron or zinc. For example, when a mixture of benzyl chloride and benzene are treated in the cold with aluminum chloride, a vigorous reaction takes place with elimination of hydrogen chloride resulting in the union of the phenyl and benzyl radicals to form diphenylmethane ... 

Although few examples of acylations of 1,3-butadienes have been described, Friedel-Crafts acylations of diene complexes, in particular iron tricarbonyl derivatives, can give synthetically useful yields. In acylations of iron tricarbonyl complexes with the Perrier reagent from acetyl chloride and aluminum chloride, acylation occurs only at unsubstituted terminal carbons (Scheme 18). ° The primary product is... 

The use of metal in Friedel-Crafts acylation has been patented for the production of diketones, significant in the field of material chemistry. Thus, l,4-bis(4-methoxybenzoyl)benzene 36 can be synthesized by double acylation of anisole with terephthaloyl chloride 35 in the presence of zinc or iron metal (Scheme 3.8). ... 

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