Benzoyl halides

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

Azoles containing a free NH group react comparatively readily with acyl halides. yV-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (75) — (76) or type (79)—>(80) or (81). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. 

Crunden and Hudson80, by comparison of solvolysis rates in formic acid and aqueous acetone (although the same authors have stated that this may be coincidental), obtained a value of 40% SN1 participation in aqueous acetone (65%) they also estimated the contribution of the SN1 route to the solvolysis of substituted benzoyl halides (Table 6). It must, however, be emphasized that the nature of the intermediate trapped in the work of Gold et al81 could either be the acylium ion RCO+ or the hydrated acylium ion [RC0H20]+. 

Bevan and Hudson86 have reported that the hydrolysis of benzoyl fluoride is acid-catalysed and follows the [H30+], whereas other unhindered benzoyl halides do not. A parallel situation is found with the benzyl fluoride and chloride. Satchell87 has likewise demonstrated the hydrolysis of acetyl fluoride and chloride to be acid-catalysed. 

Swain and Scott56 have measured the knC lkHF ratio in neutral or slightly acidic solutions for the hydrolysis of acetyl and benzoyl halides and compared them with those for triphenylmethyl halides. Values for the triphenyl-methyl halides are — 104 greater than those for acyl halides (Table 10) reflecting the tendency for C-X bond breaking to be more complete than O-C formation at the transition state of trityl hydrolysis and the opposite tendency with the benzoyl halides. The C-F bond is harder to break but the carbon atom is made more electropositive. 

Note, however, that the comparison is with measurements for the benzoyl halides in a more aqueous medium than the acetyl halides and that this would favour a greater contribution from the unimolecular mechanism in the benzoyl halides. 

Since benzoyl chloride reacts by a mechanism which is either a combination of Sn1/Sn2 (unimolecular/bimolecular) or some intermediate mechanism, a great deal of work has been directed towards elucidation of the factors which control its reactivity. In the context of the 3 and 4-substituted benzoyl halides, it is seen from the evidence of Hammett plots to react predominantly by a bimolecular mechanism in solvents of low polarity and by a unimolecular mechanism in solvents of high polarity. 

Hi) Reduction of Glycosyl Halides with Radical Rearrangement. The reduction of acetylated or benzoylated halides or selenides with a low concentration of tributylstannane leads to 2-deoxy sugar derivatives (Scheme 11). The driving force of this radical reaction is the 1,2-cA-selective migration of an ester group because of the stabilization of the radical at C-2.46... 

A similar synthesis can be used to generate DBr from benzoyl bromide if it is desired to study DBr and HBr in addition or as an alternative to DCl and HCl. In fact, if an equimolar mixture of the benzoyl halides is used along with D2O, which is about 95 percent D, the product mix will contain all isotopic forms with reasonable intensity ratios for an infrared scan of aU four species in a single ceU. Such a mixture can also be used for the determination of equilibrium constant Kp for the H D exchange reaction... 

Earlier work of this school was concerned to establish heats of formation of halogen-containing organic compounds by measuring heats of hydrolysis. Heats of hydrolysis of acetyl fluoride, chloride, bromide, and iodide402 of the chloro-substituted acetyl chlorides oi of the benzoyl halides and of chloral and bromal 3 have also been made. Comparison with heats of formation derived from heats of combustion is not normally possible, but there is a large discrepancy between the two methods for benzoyl chloride, where an early combustion measurement is available, in the sense that the determined heat of combustion appears to be about 14 kcal low. 

Palladium pincer complex 115-catalyzed selenylation of propargyl, allyl, benzyl, and benzoyl halides could be achieved under mild reaction conditions employing trimethylstannylphenylselenide 116 as selenylating agent <2005JOC9215>. 

Kinetic studies of the acylation of imidazoles with benzoyl halides and sulfonyl halides have been carried out. In acetonitrile, benzoyl fluoride reacts with imidazole in a mixed third- and fourth-order reaction i.e., the rate-determining transition state contains the acid fluoride and two or three molecules of imidazole. With benzoyl chloride in benzene a second-order equation is followed similar to the aroylation of anilines ... 

It is interesting to note that the hydrolysis of unhindered benzoyl chlorides is not catalyzed by acids, but benzoyl fluoride is acid catalyzed and follows Kq (Bevan and Hudson, 1953). Similarly, acid catalysis of benzyl fluoride hydrolysis which follows occurs (Swain and Spalding, 1960), but no acid catalysis of benzyl chloride hydrolysis is known. Furthermore, benzyl halide reactions show non-linear pa correlations (Hudson and Klopman, 1962 Hill and Fry, 1962 Swain and Langsdorf, 1951). Although much less work has been carried out on benzoyl halides, it would appear then that nucleophilic reactions with benzoyl halides resemble, in many respects, nucleophilic reactions with benzyl systems, including the considerable uncertainty as to the S l or bimolecular nature of these reactions (Thornton, 1964). 

Areneselenyl magnesium bromide has been reported to react with /7-substituted benzoyl halides, giving aromatic selenol esters " as the first examples exhibiting liquid crystal properties (equation 2). ... 

In addition to benzoyl chloride, a number of mono- and disubstituted benzoyl halides have been in Reissert compound... 

Kinetic studies of the acylation of imidazoles with benzoyl halides and sulfonyl halides have been carried out. In acetonitrile, benzoyl fluoride reacts with imidazole in a mixed third- and fourth-order reaction ... 

In addition to benzoyl chloride, a number of mono- and disubstituted benzoyl halides have been used16,18,19,21,29,36,38,46,47 in Reissert compound formation, as have acyl halides of furan-34 and thiophene-l-carboxlic acids.34,48 Besides simple aliphatic carboxylic acid halides, some co-haloacyl halides30,48,49 and pentafluorophenylacetyl chloride48 have been used. 4,4 -Oxydibenzoyl chloride with isoquinoline gave the Reissert compound 14.38... 

According to the different donor properties found in this group of solvents a distinction may be made between (a) oxyhalides with low donor numbers including carbonyl chloride, nitrosyl chloride, thionyl chloride, sulphuryl chloride, acetyl and benzoyl halides and (b) oxyhalides with medium donor numbers, namely phosphorus oxychloride, selenium oxychloride and phenyl phosphonic halides, the latter having donor properties approaching those of water or of the ethers. 

Table 2. Reaction between benzoyl halides and morpholine.

Orientation of the incoming acyl group in Friedel-Crafts acylations can be quite sensitive to the reaction solvent and other procedural variables. In general, however, para attack predominates for alkylbenzenes. The percentage of ortho attack increases with the electrophilicity of the acylium ion and approaches 1 1 with such less selective species as formyl and 2,4-dinitrobenzoyl ions. For simple alkanoyl and benzoyl halides, the o p ratio is usually 1 20 or higher. ... 

Reductive elimination of RCl from [R(X)RhCl(CO)L2] (which occurs during the decarbonylation of acid halides using rhodium catalysts) has been assumed to involve a trans stereochemistry the fact that the yields of chlorobenzene and bromobenzene from benzoyl halides rise as the cone angle of the phosphine, L, is decreased, confirms this point of view. " ... 

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