Acyl bromides from carboxylic acids

The procedure described here allows for a convenient and efficient preparation in very high yields of large quantities of bromides from carboxylic acids containing an olefinic functionality. The Hunsdiecker reaction is traditionally accomplished by treating anhydrous silver carboxylates with bromine or iodine.2 Heavy metal salts such as mercury,3 lead,4 and thallium5 have also been used successfully as well as tert-butyl hypoiodite.6 The major disadvantages associated with the above methods, such as use of heavy metal salts and non-tolerance towards olefins, has led to the development of a more versatile method using O-acyl thiohydroxamates.7 8 The O-... 

Dehydration. This reagent is useful for synthesis of acyl azides from carboxylic acids, NaCN, and pyridine, with tetrabutylammomum bromide as catalyst (75-95% yield). In combination with pyridine, it effects dehydration of oximes to nitriles in 80-90% yield, P-Lactams can be prepared directly in 40-75 )t yield from carboxylic acids and imines with the reagent (1 equiv,) and triethylamine (excess). In general, a mixture of cis- and rra/j5-azetidinones is formed. 

Dehydration.1 This reagent is useful for synthesis of acyl azides from carboxylic acids, NaCN, and pyridine, with tetrabutylammonium bromide as catalyst (75-95% yield). In combination with pyridine, it effects dehydration of oximes to nitriles in 80-90% yield. 

In addition to acyl chlorides and acyl bromides, there are a number of milder and more selective acylating agents which can readily prepared from carboxylic acids, hnidazolides, the /V-acyl derivatives of imidazole, are examples.108 Imidazolides are isolable substances and can be prepared directly from the carboxylic acid by reaction with... 

In a direct route from carboxylic acids to acyl azides diphenyl phosphorazidate is used probably the reaction passes through a cyclic transition state (Scheme 41). With aromatic and heteroaromatic educts, yields as high as 75% may be obtained. If aliphatic acids are treated under the same conditions, the corresponding azides are, however, immediately transformed into urethanes via isocyanates. Aroyl azides can also be obtained in excellent yields by reaction of carboxylic acids with NaNa and phenyl di-chlorophosphate in the presence of tetrabutylammonium bromide or pyridine (Scheme 41). ... 

Conductivity measurements have revealed that DMF and carboxylic acid chlorides form salt-like adducts (22) in an equilibrium reaction (equation 12). Such adducts can be prepared either from DMF and acid halides (chlorides and bromides) or from chloromethyleneiminium salts and salts of carboxylic acids. Acyloxyiminium salts (23) can be prepared in the pure state by reacting acid amides with carboxylic acid chlorides in the presence of silver trifluoromethanesulfonate (equation 13). Salts of type (24 equation 14) are regarded as being intermediates in the synthesis of ketones from carboxylic acids and Grignard reagents in the presence of a-chloroenamines as well as in the preparation of acyl halides (F, Cl, Br, I) by action of a-haloenamines on carboxylic acids. ... 

A convenient one-pot procedure for the preparation of a-bromo thioesters from carboxylic acids based on the HVZ reaction was developed by H.-J. Liu and co-workers.The neat carboxylic acid was mixed with 0.4 equivalents of PBrs, the resulting mixture was heated to 100-120 °C in an oil bath and 1.2 equivalents of liquid bromine was added in 1.5h. In the same flask, now containing the a-bromo acyl bromide, the solution of the thiol in dichloromethane was added to give the desired a-bromo thioesters in high yield. 

Introduction. The Ph3PBr2 adduct was first used in synthesis in 1959 for the preparation of alkyl and acyl bromides from alcohols and carboxylic acids, and for the dehydration of amides and oximes to nitriles. Since then it has been widely employed as a versatile reagent for a number of synthetic reactions. 

These reactions are most important for the preparation of acyl fluorides.1061 Acyl chlorides and anhydrides can be converted to acyl fluorides by treatment with polyhydrogen fluoride-pyridine solution996 or with liquid HF at -10°C.1062 Formyl fluoride, which is a stable compound, was prepared by the latter procedure from the mixed anhydride of formic and acetic acids.1063 Acyl fluorides can also be obtained by reaction of acyl chlorides with KF in acetic acid1064 or with diethylaminosulfur trifluoride (DAST).1065 Carboxylic esters and anhydrides can be converted to acyl halides other than fluorides by the inorganic acid halides mentioned in 074, as well as with Ph3PX2 (X = Cl or Br), 066 but this is seldom done. Halide exchange can be carried out in a similar manner. When halide exchange is done, it is always acyl bromides and iodides that are made from chlorides, since chlorides are by far the most readily available.1067... 

The mercapto group of 9-mercapto-4//-pyrido[ 1,2-a]pyrimidin-4-ones 513 was alkylated with (het)aralkyl bromides and chlorides in the presence of potassium carbonate in dimethylformamide at ambient temperature for several hours. It also was acylated with carboxyl chlorides in the presence of potassium carbonate in acetone at room temperature or with mixed anhydride, prepared from aryl carboxylic acid and ethyl chloroformate,... 

Intramolecular acylation of alkylsilanes. Cyclopentanones can be prepared by ring closure of 5-(trimethylsilyl)alkanoyl chlorides mediated by AlCl,. The starting materials are readily available from alkylation of the dianion of a carboxylic acid with a 3-(trimethylsilyl)alkyl bromide or iodide (equation 1). 

The conversion of a carboxylic acid to its halide is usually accomplished by thionyl chloride or phosphorus halides. Phosphorus trichloride and glacial acetic acid give acetyl chloride (67%). The other product is phosphorus acid. Phosphorus pentachloride is converted to phosphorus oxychloride (b.p. 103°), from which the acyl halide is sometimes separated with difficulty. This reagent, however, finds use in the preparation of certain higher-molecular-weight halides. .. Most acyl bromides are made from phosphorus tribromide. ... 

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