Friedel-Crafts acylation See

Acid chlorides are easily converted to 1° alcohols and aldehydes (see Section 5.7.21) and 3° alcohols and ketones through the choice of appropriate metal hydride and organometallic reagents (see Section 5.5.5). Acid chloride reacts with benzene in the presence of Lewis acid (AICI3) in Friedel-Crafts acylation (see Section 5.5.6). 

For reviews of Friedel-Crafts acylation, see Olah Friedel-Crafts and Related Reactions Wiley New York, 1963-1964, as follows vol. 1, Olah, pp. 91-115 vol. 3, Gore, pp. 1-381 Peto, pp. 535-910 Sethna, pp. 911-1002 Jensen Goldman, pp. 1003-1032. For another review, see Gore Chem. Ind. (London) 1974, 727-731. 

Friedel-Crafts acylations (see Chapter 2) are used to prepare aromatic ketones. The preparation of acetophenone from benzene and acetyl chloride is a typical Friedel-Crafts acylation. 

Most of the reactions of the phenothiazinyl ketones discussed here were carried out on compounds of the 2 series readily available by Friedel-Crafts acylation (See Section V,A,4,c) many products derived from these ketones are of pharmacological importance. 

When a phenyl ring on the backbone of polystyrene (represented by the solid sphere) is reacted with benzoyl chloride and aluminum chloride, the product is the benzoyl derivative 167 (this is a Friedel-Crafts acylation see Chapter 21, Section 21.3.3). If reacted with 168, the product is 169 (an acyl addition reaction of an organolithium reagent see Chapter 18, Section 18.4). When the methyl group of the pyridine unit in 169 is treated with phenyllithium to form the (pyridyllCHgLi derivative, reaction with formaldehyde leads to 170. If 170 is linked to iV-benzoyl 2 -0-isobutyladenosine-3 -monophosphate (171), the product is 172, in which the first nucleotide is bound to the polymer via the 3 position. 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

With a substituted aromatic ring compound 2, mixtures of isomeric coupling products may be formed the ort/zo-product usually predominates. The rules for regiochemical preferences as known from electrophilic aromatic substitution reactions (see for example Friedel-Crafts acylation), do not apply here. 

In an initial step the reactive formylating agent is formed from N,N-dimethylformamide (DMF) 2 and phosphorus oxychloride. Other N,N-disubstituted formamides have also found application for example A -methyl-A -phenylformamide is often used. The formylating agent is likely to be a chloromethyl iminium salt 4—also called the Vilsmeier complex (however its actual structure is not rigorously known)—that acts as the electrophile in an electrophilic substitution reaction with the aromatic substrate 1 (see also Friedel-Crafts acylation reaction) ... 

Friedel-Crafts acylation reaction and,557-558 resonance in, 558 Acyl group, 557, 686 names of, 753 Acyl phosphate, 816 naming, 788 Acylation (aromatic), see... 

Hydroxyalkyl)porphyrins,84-85 I07b 109 easily accessible from porphyrins by Friedel-Crafts acylation and subsequent reduction, undergo a stereoselective Claisen rearrangement with N,N-dimethylacetamide dimethyl acetal. The substitution pattern and the stereochemical arrangement of the derived chlorins match those of naturally occurring chlorins9 (see Section 1.2.1.2.). 

Protonation and deprotonation reactions of corroles have already been mentioned (see Introduction). Attempts to achieve electrophilic substitution reactions, at the corrole, e.g. Friedel-Crafts acylation, have been unsuccessful.1 Heating corroles with acetic anhydride yields the corresponding 21-acetyl derivatives l.8a,b... 

Aromatic compounds, 13 108-109 13 680. See also Aromatics acylation of, 12 173-181 amination of, 12 184 arylation of, 12 170-171 Cycloalkylation of, 12 169 in diesel fuel, 12 425 formylation of, 12 178 Friedel-Crafts acylation of, 12 174 Friedel-Crafts alkylation of, 12 164 nitration of, 12 182-183 oxidative coupling of, 19 654 sulfonation of, 12 181 sulfonation reagents for, 23 521-524 Aromatic-containing polymers, sulfonation of, 23 535-536... 

A similar problem of complex formation may be encountered if either amino or phenol groups are present in the substrate, and the reaction may fail. Under such circumstances, these groups need to be blocked (protected) by making a suitable derivative. Nevertheless, Friedel-Crafts acylations tend to work very well and with good yields, uncomplicated by multiple acylations, since the acyl group introduced deactivates the ring towards further electrophilic substitution. This contrasts with Friedel-Crafts alkylations, where the alkyl substituents introduced activate the ring towards further substitution (see Section 8.4.3). 

Cyclizations can also be carried out with an esterified oligomer of phosphoric acid called polyphosphate ester. This material is soluble in chloroform.49 (See entries 11 and 12 in Scheme 11.4.) Another reagent of this type is trimethylsilyl polyphosphate.50 Neat methanesulfonic acid is also an effective reagent for intramolecular Friedel-Crafts acylation.51 (See entry 13 in Scheme 11.4.)... 

The first agent of this class to be introduced in the clinic, haloperidol (18-8), interestingly shares the 4-phenylpiperidine structural fragment found in the central analgesic agent meperidine and its derivatives (see Chapter 7). The former compound may well have been discovered in the course of further SAR studies on the opiate [20]. An unusual synthesis of haloperidol starts with the product (18-1) from Friedel-Crafts acylation of 4-fluorobenzene with succinic anhydride. Successive protection of the... 

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