Aromatic acylation mixture

In connection with the elaboration of specific procedures for the manufacture of both of the isosorbide mononitrates, methods were developed to shift, with high regioselectivity, the course of the acylation reaction either towards the 5 (endo) or the 2 (exo) position, depending on the conditions applied.104-106 Thus, isosorbide 5-acylates are obtained in 70-85% yield when 3 is treated with the appropriate acid anhydride in the presence of lead(II) oxide or acetate for 20 to 40 h at room temperature. To avoid transesterifications to the appropriate 2-acylate, the workup procedures, especially during the distillation, have to be conducted under strictly neutral conditions. The contrary effect, a remarkable enrichment by the isosorbide 2-acylate (up to 90%) is realized by a transesterification process mediated by a small proportion of sodium or potassium carbonate, hydroxide, or meth-oxide, which are added to the acylation mixture from isosorbide at HOMO0, and subsequent removal of the 2-acylate by vacuum distillation.104 These two regioselective acylation methods may be used for aliphatic, as well as for aromatic, carboxylic acid anhydrides. 

Acylation of anisole with A AN is carried out in a mixture of GALDEN SV 135, a suitable fluorous solvent, and chlorobenzene in the presence of hafnium tetra[bis(perfluorooctanesulfonyl)amide] (1% mol) at 70°C-120°C for 1 to 5 h, giving para-methoxyacetophenone in 80% yield and 100% selectivity. It is significant to underline that aluminum chloride gives the mentioned product in only 2% yield under the present mild reaction conditions. The catalyst can be very easily recycled by directly reusing the lower fluorous catalytic phase in the successive reaction with another mixture of reactants, affording the product more than three times without decrease in catalytic activity. The catalytic process can be applied to dimethoxybenzenes and mesitylene with both aliphatic and aromatic acyl chlorides and anhydrides (80%-97% yield). Benzoylation of toluene gives para-methylbenzophenone in 35% yield. 

Table 4.25 Aromatic acylation with carboxylic acids in the presence of graphite-para-toluenesulfonic acid mixture...

It is thus particularly suitable for acylation by the more difficultly hydrolysable aromatic acyl chlorides. It usually suffices to shake a suspension of the amine in sodium hydroxide solution with the acid chloride for some time at room temperature the mixture is then sometimes heated for a short time to complete the reaction and hydrolyse unchanged acyl chloride the amide is finally filtered off or extracted with an organic solvent. Since the mixture should remain alkaline to the end of the reaction and a small proportion of the chloride will be hydrolysed, an approximately 25% excess of both the alkali and the chloride is usually used. 

Izumi et al. pioneered the use of heteropoly acids as catalysts for aromatic acylation. Silica-supported acids H4[SiWi204o] and H3[PWi204o] were found to effectively catalyse the acylation of p-xylene with benzoyl chloride. Cs2.5Ho.5[PWi204o] showed high efficiency in the acylation of activated arenes, such as p-xylene, anisole, mesitylene, etc., by acetic and benzoic anhydrides and acyl chlorides. This catalyst provided higher yields of acylated arenes than the parent acid H3[PWi204o], the latter being partly soluble in the reaction mixture. ... 

Iodine (2% mol) can be used as a catalyst for the acetylation of electron-rich aromatic compounds with aliphatic and aromatic acyl chlorides or anhydrides in 25-93% yields [8]. In successful acylations, the violet-colored refluxing mixture disappears after 15-30 min. Heterocyclic compounds such as furan and thiophene derivatives undergo easy acylation in the presence of variable amounts of iodine. The process is of particular synthetic interest since these heterocycle compounds are... 

Liquid crystal polyesters are made by a different route. Because they are phenoHc esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenoHc hydroxyl groups are acylated with a lower aHphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxyHc acid, sometimes in the presence of a catalyst. The phenoHc polyester forms readily as the volatile lower acid distills from the reaction mixture. Many Hquid crystal polymers are derived formally from hydroxyacids (97,98) and thein acetates readily undergo self-condensation in the melt, stoichiometric balance being automatically obtained. 

The steric bulk of the three iodine atoms in the 2,4,6-triiodoben2ene system and the amide nature of the 1,3,5-substituents yield rotational isomers of the 5-A/-acyl-substituted 2,4,6-triiodoisophthalamides. Rotational motion in the bonds connecting the side chains and the aromatic ring is restricted. These compounds also exhibit stereoisomerism when chiral carbon atoms are present on side chains. (R,5)-3-Amino-l,2-propanediol is incorporated in the synthesis of iohexol (11) and ioversol (12) and an (3)-2-hydroxypropanoyl group is used in the synthesis of iopamidol (10). Consequendy, the resulting products contain a mixture of stereoisomers, ie, meso-isomers, or an optical isomer. 

The nitrogen of aHphatic and aromatic amines is alkylated rapidly by alkyl sulfates yielding the usual mixtures. Most tertiary amines and nitrogen heterocycles are converted to quaternary ammonium salts, unless the nitrogen is of very low basicity, eg, ia tn phenylamine. The position of dimethyl sulfate-produced methylation of several heterocycles with more than one heteroatom has been examined (22). Acyl cyanamides can be methylated (23). Metal cyanates are converted to methyl isocyanate or ethyl isocyanate ia high yields by heating the mixtures (24,25). 

Acylation with aromatic acid chlorides was believed to occur on carbon 91). The dibenzoylation of the enamine (113) with benzoyl chloride in the presence of triethylamine has, however, been shown to give a mixture of three products (92). The major components are the cis and Irons isomers of the O-acylated enamino ketone (Ola and b) and the minor isomer is the 2,6-diacylated enamine (132). 

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. 

Reaction conditions reflux of a mixture of the aromatic compound, N-benzoylimid-azole, and trifluoroacetic acid in a molar ratio of 1 1.2 10. This method for acylating aromatic hydrocarbons works without the use of classical Friedel-Crafts catalysts. 

Acyl chlorides, Aromatic hydrocarbons EfFenberger, F. et al., Angew. Chem. (Intern. Ed.), 1972, 11, 300 Addition of catalytic amounts (1%) of the acid (stronger even than perchloric acid) to mixtures of acyl chlorides and aromatic hydrocarbons causes more or less violent evolution of hydrogen chloride, depending on the reactivity of the Friedel-Crafts components. 

The heat of decomposition (238.4 kJ/mol, 3.92 kJ/g) has been calculated to give an adiabatic product temperature of 2150°C accompanied by a 24-fold pressure increase in a closed vessel [9], Dining research into the Friedel-Crafts acylation reaction of aromatic compounds (components unspecified) in nitrobenzene as solvent, it was decided to use nitromethane in place of nitrobenzene because of the lower toxicity of the former. However, because of the lower boiling point of nitromethane (101°C, against 210°C for nitrobenzene), the reactions were run in an autoclave so that the same maximum reaction temperature of 155°C could be used, but at a maximum pressure of 10 bar. The reaction mixture was heated to 150°C and maintained there for 10 minutes, when a rapidly accelerating increase in temperature was noticed, and at 160°C the lid of the autoclave was blown off as decomposition accelerated to explosion [10], Impurities present in the commercial solvent are listed, and a recommended purification procedure is described [11]. The thermal decomposition of nitromethane under supercritical conditions has been studied [12], The effects of very high pressure and of temperature on the physical properties, chemical reactivity and thermal decomposition of nitromethane have been studied, and a mechanism for the bimolecular decomposition (to ammonium formate and water) identified [13], Solid nitromethane apparently has different susceptibility to detonation according to the orientation of the crystal, a theoretical model is advanced [14], Nitromethane actually finds employment as an explosive [15],... 

A variation of this method led to the generation of bis-benzimidazoles [81, 82], The versatile immobilized ortho-phenylenediamine template was prepared as described above in several microwave-mediated steps. Additional N-acylation exclusively at the primary aromatic amine moiety was achieved utilizing the initially used 4-fluoro-3-nitrobenzoic acid at room temperature (Scheme 7.72). Various amines were used to introduce diversity through nucleophilic aromatic substitution. Cyclization to the polymer-bound benzimidazole was achieved by refluxing for several hours in a mixture of trifluoroacetic acid and chloroform. Individual steps at ambient temperature for selective reduction, cyclization with several aldehydes, and final detachment from the polymer support were necessary in order to obtain the desired bis-benzimidazoles. A set of 13 examples was prepared in high yields and good purities [81]. 

Carbonyl oxygen atoms of aldehydes can also be efficiently acylated by 1-acylbenzotriazoles 915 in the presence of mild bases (K2CO3, Et3N). The released benzotriazolide anions are consecutively attached to the aldehyde carbonyl carbon atoms to produce esters 944 (Equation 20). Aliphatic aldehydes react quickly at room temperature, but aromatic aldehydes require elevated temperatures. The yields are good to quantitative. The amounts of benzotriazol-2-yl isomers of esters 944 in the products mixtures is strongly dependent on the reaction conditions and the character of groups R1 and Rz, and it may vary from 5% to 25% <1999JHC777>. 

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). 

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