The use of clays has unsurprisingly led to patented procedures for the use of montmorillonite in the synthesis of amides and this approach will be an important one for the preparation of amides that do not possess significantly sensitive functional groups elsewhere in the molecule. The montmorillonite catalyst had been used a couple of years earlier in a slightly less general procedure, in which an enormous range of amines were reacted with acetic, propanoic, or butanoic acids, using the acid itself as the solvent at reflux. The K-10 montmorillonite clay has also proved very popular with those attempting to develop environmentally friendly catalytic chemistry this clay has been used in the synthesis of a range of alkyl- and arylamides, by refluxing in alcohols that boil at ∼100 ☌, and it would appear to be a very powerful method, with yields typically in excess of 90%. For example, a whole range of alkyl, aryl, and heterocyclic amines were acylated with acetic acid at only a little over 100 ☌, using the HY zeolite. One major development in the direct synthesis of amides from carboxylic acids has been the discovery that clays and zeolites are able to catalyze the reaction, not only allowing the direct synthesis of amides from the corresponding acid and amine, but even bringing the temperature down, often to less than 100 ☌. The rigidity of the remainder of the structure allows the cyclization to the amide to be a straightforward process, and it is of course mechanistically similar to normal amide bond formation, although the final product does not possess the additional stability that is usually associated with the amide bond. Even more surprisingly, the reaction also occurs at room temperature at pH 4, although the amide is then observed in its hydrate form it is worth noting that this “most twisted amide” possesses an angle of around 90 ° between the carbonyl π-bond and the nitrogen lone pair, and that its reactions are essentially those of a tertiary amine and a ketone. For example, Kirby’s group demonstrated that the “most twisted amide,” based on the adamantane structure, can be prepared by simply subliming the amino acid at 80 ☌ ( Scheme 4). Nevertheless, the formation of five- and six-membered rings is often surprisingly simple provided that other factors can be brought into play to assist in the condensation. Amides are not in general accessible by the direct condensation of amines with carboxylic acids for two reasons: first, both components are readily deactivated by a transfer of a proton from the acid to the amine and second, the hydroxy unit on the carbonyl of the acid is a relatively poor leaving group.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |