Benzene acylation of, Friedel-Crafts

Dehydrogenation of alkylbenzenes, although useful in the industrial preparation of styrene, is not a general procedure and is not well suited to the laboratory preparation of alkenylbenzenes. In such cases an alkylbenzene is subjected to benzylic bromina-tion (Section 11.10), and the resulting benzylic bromide is treated with base to effect dehydrohalogenation. 

Outline a synthesis of 1-phenylcyclohexene from benzene and cyclohexene. 

Another version of the Friedel-Crafts reaction uses acyl halides instead of alkyl halides and yields aryl ketones. 

The electrophile in a Friedel-Crafts acylation is an acyl cation (also referred to as an acylium ion) and is formed on reaction of acyl chlorides with aluminum chloride in much the same way as alkyl cations are formed from alkyl halides. 

Electron delocalization in the acyl cation derived from propanoyl chloride is represented by the following two resonance contributors. Note that electron release from oxygen generates a contributing structure that satishes the octet rule and disperses the posihve charge. 

Acyl cations form by coordination of an acyl chloride with aluminum chloride, followed by cleavage of the carbon-chlorine bond. 

the industrial preparation of styrene from benzene and ethylene does not involve vinyl chloride but proceeds by way of ethylbenzene. 

Most stable resonance form oxygen and carbon have octets of electrons 

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Friedel-Crafts acylation of benzene with benzoyl chloride (CgH5CCl) (j) Nitration of the product from part (1)... 

In-situ IR-spectroscopic characterization of the Friedel-Crafts acylation of benzene in ionic liquids derived from AICI3 and FeCl3 showed that the mechanism of the reaction in ionic liquids was the same as that in 1,2-dichloroethane (128). The immobilization of ferric chloride-containing ionic liquid onto solid supports (e.g., silica and carbon) however failed to catalyze the acylation reaction, because leaching was a serious problem. When the reaction was carried out with gas-phase reactants, catalyst deactivation was observed. 

The antiasthamtic activity of the sulfur-free substituted long chain fatty acid seratrodast (59-5) is attributed to the antagonism of thromboxanes, whose structures also include a fatty side chain, rather than to leukotrienes. Friedel-Crafts acylation of benzene with the acid chloride from monomethyl pimelate (59-1) leads to... 

The structure of the pyridazine-based antidepressant agent minaprine (34-6) departs markedly from both the older tricyclic drugs and the more recent selective serotonin re-uptake inhibitors. There is evidence that the compound acts via a dopa-mimetic route. Friedel-Crafts acylation of benzene with itaconic anhydride (34-1) leads to the keto-acid (34-2). Condensation with hydrazine leads to the formation of the hydrazine and hydrazide bonds the double bond shifts into the ring to give the fully unsaturated pyridazinone (34-3) this is then converted to the chloride (34-4) in the usual way. The displacement of halogen by the amine on 3-(A -morpho-lino)propylamine (34-5) affords (34-6) [36]. 

The use of acyl chlorides in Friedel-Craft acylations of benzene rings, as well as their reactions with organometallics and reductions to aldehydes, has been discussed in Section 15.2. 

Phenyl heptyl ketone has been prepared by the Friedel-Crafts acylation of benzene with octanoyl chloride.6 It is also a product of the thermal decomposition of the mixed ferrous salts of benzoic and octanoic acids.7... 

Recalling that arylamines are normally prepared by reduction of nitroarenes, we see that ethyl m-nitrophenyl ketone is a pivotal synthetic intermediate. It is prepared by nitration of ethyl phenyl ketone, which is analogous to nitration of acetophenone, shown in Section 12.16. The preparation of ethyl phenyl ketone by Friedel-Crafts acylation of benzene is shown in Section 12.7. 

Attempted Friedel-Crafts acylation of benzene with t-BuCOCl gives some of the expected ketone, as a minor product, and also some f-butyl benzene, but the major product is the disubstituted compound C. Explain how these compounds are formed and suggest the order in which the two substituents are added to form compound C. 

There is one way to avoid umpolung and that is to make the disconnection outside the 1,4 relationship. As it happens, we have already seen this strategy in action (p, 799), It involves a Friedel-Crafts acylation of benzene (Chapter 22) with a cyclic anhydride and leads directly to this... 

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... 

Strategy To identify the carboxylic acid chloride used in the Friedel-Crafts acylation of benzene, break the bond between benzene and the ketone carbon and replace it with a -Cl. 

In the Friedel-Crafts acylation of benzene, the above procedure gave only poor yield, whereas a new catalyst system, Hf(OTf)4 and CF3SO3H, was found to catalyze the reaction of even deactivated benzenes, e.g. chlorobenzene and fluorobenzene (Eq. 13) [20]. 

Essentially every analog and derivative prepared in the project was ultimately derived from the corresponding 3-chloro-pyri-dazine. With the exception of a few 3-chloropyridazines which originated from a Friedel-Crafts acylation of benzene, the large majority of chloropyridazines were prepared by a sequence based on the addition of the masked acyl anion equivalent of a benzaldehyde to the appropriately substituted acrylate ester. 

In the presence of a stoichiometric amount of SbCls, Friedel-Crafts acylation proceeds with acyl hahdes and acid anhydrides [47], SbCls also promotes the Fries rearrangement of phenyl acetates [48], The electrophilic acylation of fluoro-olefins with acetyl fluoride or benzoyl fluoride is promoted by SbFs in liquid SOy [49], The Friedel-Crafts acylation of benzene and electron-rich arenes is successfully catalyzed by SbCl5-AgClO4 [50], SbCl, Ar.BCl [51], SbCl5-LiClO4 [52], or CaCI, AgSbFg [53] (Scheme 14,19), Acyl chlorides, acid anhydrides, and acyl enolates are used as sources of acyl groups. 

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