Acylation and Alkylation Reactions

The general feature in these reactions under sonication is the possibility of using solid bases even in apolar solvents, with the advantage of minimizing side reactions. Alkali carbonates can be used with success. 

The alkylation of 5-(4-hydroxyphenoxy)-l/f-l,2,3-triazoles (147) under alkaline conditions exclusively yields the isomeric N(2) and N(3) alkylation products (148) and (149) (Equation (9)). For R = PhCH2, the N(2) and N(3) isomers are obtained in almost equal amounts, but for R = PhjC, only 1% of the N(3) isomer is formed because of steric hindrance. No N(l) alkylation is observed. Acylation and sulfonation of (147) under similar conditions results in attack at the phenolic oxygen 82JHCl 147 . Reaction of benzotriazole with 2-chlorothiophen-3-ones (150) in acetic acid gives 5-(benzotriazol-l-yl)-3-hydroxythiophene-2-carboxylates (151) (Equation (10)) 87JHC1301 . 

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Neither Friedel-Crafts acylation nor alkylation reactions can be earned out on mtroben zene The presence of a strongly deactivating substituent such as a nitro group on an aromatic ring so depresses its reactivity that Friedel-Crafts reactions do not take place Nitrobenzene is so unreactive that it is sometimes used as a solvent m Friedel-Crafts reactions The practical limit for Friedel-Crafts alkylation and acylation reactions is effectively a monohalobenzene An aromatic ring more deactivated than a mono halobenzene cannot be alkylated or acylated under Friedel-Crafts conditions... 

Another important use of BCl is as a Ftiedel-Crafts catalyst ia various polymerisation, alkylation, and acylation reactions, and ia other organic syntheses (see Friedel-Crafts reaction). Examples include conversion of cyclophosphasenes to polymers (81,82) polymerisation of olefins such as ethylene (75,83—88) graft polymerisation of vinyl chloride and isobutylene (89) stereospecific polymerisation of propylene (90) copolymerisation of isobutylene and styrene (91,92), and other unsaturated aromatics with maleic anhydride (93) polymerisation of norhornene (94), butadiene (95) preparation of electrically conducting epoxy resins (96), and polymers containing B and N (97) and selective demethylation of methoxy groups ortho to OH groups (98). 

Boron Bromide. Approximately 30% of BBr produced in the United States is consumed in the manufacture of proprietory pharmaceuticals (qv) (7). BBr is used in the manufacture of isotopicaHy enriched crystalline boron, as a Etiedel-Crafts catalyst in various polymerization, alkylation, and acylation reactions, and in semiconductor doping and etching. Examples of use of BBr as a catalyst include copolymerization of butadiene with olefins (112) polymerization of ethylene and propylene (113), and A/-vinylcarbazole (114) in hydroboration reactions and in tritium labeling of steroids and aryl rings (5). 

Compared to the chemical modification reactions of PS, alkylation and acylation reactions are preferred to other reactions, such as halogenation, nitrolation, sulfo-nation, amination, and chloromethylation, etc. because the obtained polyfunctional PS has higher physico-me-chanical properties. 

Many variations of the reaction can be carried out, including halogenation, nitration, and sulfonation. Friedel-Crafts alkylation and acylation reactions, which involve reaction of an aromatic ling with carbocation electrophiles, are particularly useful. They are limited, however, by the fact that the aromatic ring must be at least as reactive as a halobenzene. In addition, polyalkylation and carbocation rearrangements often occur in Friedel-Crafts alkylation. 

These alkylation and acylation reactions are important because Friedel-Crafts alkylation and acylation (11-12, 11-14) cannot be applied to most nitrogen heterocycles. See also 13-15. 

Scheme 7.8 Microwave assisted N-alkylation and acylation reactions...

Zinc chloride exchanged clay catalysts have been reported to be highly active for the Friedel-Crafts alkylation and acylation reactions these are commercially sold by Contract Catalysts under the name Envirocats. These are montmorillonite catalysts modified by ZnCU and FeCli. Some of the reported examples of Friedel-Crafts reactions are given below there are claims that some of the processes are commercially practised. 

BF3 is an effective reagent for various kinds of reaction such as Friedel-Crafts alkylation and acylation reactions (Scheme 63),291 cyclization reactions, rearrangement,292 Diels-Alder reactions,293 and aldol reactions. 

Following are several commercially available fluoromonomers (1-4) that contain functional groups and have been utilized to make polymeric membranes for ion separations6"9 or as catalysts for aromatic alkylation and acylation reactions.1011 They are also convenient starting precursors, allowing for further functionalization reactions. 

Kaldor [49 i, 55] demonstrated the advantages of applying solid-supported scavengers to the preparation of parallel arrays in a multi-step fashion. In these studies he examined the clean-up of multiple amine alkylation and acylation reactions using a variety of immobilized electrophilic and nucleophilic scavenger reagents including an amine, isocyanate, aldehyde and acid chloride (Tab. 2.1). 

Undesirable intermolecular reactions can be avoided during certain synthetic conversions. Thus it is often useful to carry out C-alkylation and C-acylation of compounds that form enolate anions, for example, esters with a-hydrogens. Such reactions are often complicated by self-condensation since the enolate anion can attack the carbonyl group of a second ester molecule. Attachment of the enolizable ester to a polymer support at low loading levels allows the alkylation and acylation reactions (Eq. 9-79) to be performed under... 

N-Alkylation and acylation reactions show the normal behavior for cyclic amines. 

The intermediacy of an anhydro base (57) was referred to in Scheme 46. Analogous anhydro bases (pyridone methides) can be formed by deprotonation of quaternary salts of 2- and 4-benzylpyridines and the like. The pyridone methides are usually highly reactive and not readily isolable some stable examples are shown in Scheme 49. Pyridine methides are intermediates in the base-catalyzed alkylation and acylation reactions of pyridinium salts at the exocyclic carbon. Compounds of type (60) have been estimated to have 25-30% dipolar character. Protonation of (60) occurs at the 2 - and 3 -positions in the ratio 4 1 respectively (70JCS(C)800). 

In addition to those methods described in CHEC(1984) and CHEC-II(1996) (primarily alkylation and acylation reactions), Vicentini <1996T7179> has shown that 5-methylimidazo[4,5-f]pyrazole 28 can undergo electrophilic attack on nitrogen by hydroxylamine 0-sulfonic acid to yield the 4-amino species 29 (Equation 1). 

A 1 2 mixture of l-methyl-3-ethylimidazolium chloride and aluminum trichloride, an ionic liquid that melts below room temperature, has been recommended recently as solvent and catalyst for Friedel-Crafts alkylation and acylation reactions of aromatics (Boon et al., 1986), and as solvent for UV/Vis- and IR-spectroscopic investigations of transition metal halide complexes (Appleby et al., 1986). The corresponding 1-methyl-3-ethylimidazolium tetrachloroborate (as well as -butylpyridinium tetrachlo-roborate) represent new molten salt solvent systems, stable and liquid at room temperature (Williams et al., 1986). 

In the acylation of alkylbenzene the product almost always is the para isomer. The synthesis of (4-fert-butylphenyl)ethanone illustrates this as well as, the sequential use of alkylation and acylation reactions ... 

Several important reactions of arenols involve aromatic substitution of arenolate ions with carbon electrophiles. In a sense, these reactions are alkylation and acylation reactions as discussed for arenes (Sections 22-4E and 22-4F). In another sense, they are alkylation and acylation reactions of enolate anions and therefore could give rise to products by C- and O-alkyla-tion, or C- and O-acylation (Section 17-4). Thus ... 

Among the oxidants that have been used to generate radicals, manganese (HI) acetate has emerged as a powerful reagent to mediate radical cyclizations.147 The manganese(III) acetate-mediated oxidation of enolizable carbonyl compounds is one of the best methods available for the cyclization of electrophilic radicals. The substrates are vety easily prepared by standard alkylation and acylation reactions. Radicals are formed with high selectivity by oxidation of acidic C—H bonds, and, because the reaction is an oxi-... 

The wide scope of application of the electrophilicity index of Parr, Szentpaly, and Liu has been reviewed.1 Applications to electrophilic aromatic substitutions discussed are few. However, some alkylation and acylation reactions do correlate well with electrophilicity values. In the case of the nitration of toluene and chlorobenzene, correlation is not very good and it is suggested2 that electrophilicity is a kinetic quantity with inherent thermodynamic information. 

The major differences in the selective properties observed in the alkylation and acylation reactions are related to the stability of the... 

The unsubstituted nitrogen atom in 1,2,4-dithiazolidines is more prone to electrophilic reactions. Both the potassium salt 11 and the initial product 12 can participate in alkylation and acylation reactions. Alkylation of salt 11 with alkyl halides is carried out in DMF or MeCN and compound 12 can react with alkyl halides in MeCN in the presence of inorganic bases (NaH, Bu OK, AcONa, NaHCOj, CS2CO3) NaHCO( proved to be the base of choice. Yields of alkylation products 26 in some cases reach 85-90%. Compound 12 was acylated by benzoyl chloride in pyridine to form the iV-benzoyl derivative 25 (Scheme 15) <2000SL1622, 20030BC3015>. 

Study of the reactivity of aromatic C-H bonds in the presence of transition metal compounds began in the 1960s despite the quite early discovery of Friedel-Crafts alkylation and acylation reactions with Lewis acid catalysts. In 1967, we reported Pd(II)-mediated coupling of arenes with olefins in acetic acid under reflux [1], The reaction involves the electrophilic substitution of aromatic C-H bonds by a Pd(II) species, as shown in Scheme 2, and this is one of the earliest examples of aromatic C-H bond activation by transition metal compounds. Al-... 

Scheme 8.11 Alkylation and acylation reactions adjacent to carbonyls.

Many alkylation and acylation reactions are most effective using anions of /3-dicarbonyl compounds that can be completely deprotonated and converted to their enolate ions by common bases such as alkoxide ions. The malonic ester synthesis and the acetoacetic ester synthesis use the enhanced acidity of the a protons in malonic ester and acetoacetic ester to accomplish alkylations and acylations that are difficult or impossible with simple esters. 

Write equations showing the expected products of the following enamine alkylation and acylation reactions. Then give the final products expected after hydrolysis of the iminium salts. 

Aluminum chloride, AICI3 Acts as a Lewis acid catalyst in Friedel-Crafts alkylation and acylation reactions of aromatic compounds (Section 16.3). 

Ionic liquids can be used as replacements for many volatile conventional solvents in chemical processes see Table A-14 in the Appendix. Because of their extraordinary properties, room temperature ionic liquids have already found application as solvents for many synthetic and catalytic reactions, for example nucleophilic substitution reactions [899], Diels-Alder cycloaddition reactions [900, 901], Friedel-Crafts alkylation and acylation reactions [902, 903], as well as palladium-catalyzed Heck vinylations of haloarenes [904]. They are also solvents of choice for homogeneous transition metal complex catalyzed hydrogenation, isomerization, and hydroformylation [905], as well as dimerization and oligomerization reactions of alkenes [906, 907]. The ions of liquid salts are often poorly coordinating, which prevents deactivation of the catalysts. 

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