Dimethylformamide as a Carbon Monoxide Source in Fast Palladium-Catalyzed Aminocarbonylations of Aryl Bromides

Abstract

Dimethylformamide (DMF) acts as an efficient source of carbon monoxide and dimethylamine in the palladium-catalyzed aminocarbonylation (Heck carbonylation) of p-tolyl bromide to provide the dimethylamide. Addition of amines to the reaction mixture in excess delivers the corresponding aryl amides in good yields. The amines employed, benzylamine, morpholine, and aniline, all constitute good reaction partners. The reaction proceeds smoothly with bromobenzene and more electron-rich aryl bromides, but electron-deficient aryl bromides fail to undergo aminocarbonylation. The reactions are conducted at 180-190 degrees C for 15-20 min with microwave heating in a reaction mixture containing imidazole and potassium tert-butoxide: the latter is required to promote decomposition of the DMF solvent at a suitable rate. The beneficial effects of controlled microwave irradiation as an energy source for the rapid heating of the carbonylation reaction mixture are demonstrated. The carbonylation procedure reported herein, which relies on the in situ generation of carbon monoxide, serves as a convenient alternative to other carbonylation methods and is particularly applicable to small-scale reactions where short reaction times are desired and the direct use of carbon monoxide gas is impractical.

Controlled Microwave Heating in Modern Organic Synthesis

“…[109][110][111][112][113] The key feature of all those protocols is the use of molybdenum hexacarbonyl as a solid precursor of carbon monoxide, which is required in carbonylation chemistry. [Mo(CO) 6 ] liberates enough CO in situ at 150 8C, for example, that rapid aminocarbonylation reactions take place (at 210 8C, CO is liberated instantaneously).…”

“…[110] Simple modifications of the general strategy outlined in Scheme 13 enabled the corresponding carboxylic acids [109] and esters [111] to be obtained instead of the amides. Further modifications by Alterman and co-workers have resulted in the use of DMF as a source of CO [112] and the use of formamide as a combined source of NH 3 and CO. [113] The latter method is useful for the preparation of primary aromatic amides from aryl bromides. In both cases, strong bases and temperatures around 180 8C (7-20 min) have to be used to mediate the reaction.…”

Creation of Novel Toxic Gas Surrogates and the Development of Safe and Facile Catalytic Reactions

“…At the time of this important discovery of CO generation from 20a, various CO surrogates were known, including formic acid, [48][49][50] paraformaldehyde, 50) N,N-dimethylformamide (DMF), 51) chloroform, 52) aldehydes, [53][54][55][56] metal carbonyl complexes, 57) acid chlorides, 58) and silacarboxylic acids. 59) Alkyl formates 60) had been also reported to act as CO surrogates.…”

The Development and Application of Sulfur Dioxide Surrogates in Synthetic Organic Chemistry

“…There are also several CO-surrogates, such as [Mo(CO) 6 ] [22] and DMF, [23] which can slowly release the required CO in situ and with the CO remaining dissolved, that satisfy all three ideal requirements of a surrogate. However, there can be dis- advantages to using surrogate reagents, for example, the use of super-stoichiometric amounts of metal reagents such as [Mo(CO) 6 ] and the associated waste generated as a result of the carrier species.…”