C-H Bond Cleavage for Complex Organic Synthesis
Breaking the C-H bonds in Hydrocarbons to Synthesize Complex Organic Molecules
The carbon-hydrogen bonds in alkanes – especially those at the ends of the molecules, where each carbon has three hydrogen atoms bound to it– are tough to “crack” if you want to change the hydrogen atoms with other atoms. Methane (CH4) and ethane (CH3CH3) are composed, specifically, of such tightly bound hydrogen atoms. In the journal Angewandte Chemie, a group of scientists has currently defined precisely how they damage these bonds while forming brand-new carbon-nitrogen bonds (amidation).
If it were possible to conveniently damage the C-H bonds in hydrocarbons, it would certainly be feasible to synthesize complex natural particles, such as pharmaceuticals, far more conveniently and directly from oil. This strategy can also offer even more pathways for recycling plastic waste. The development of carbon-nitrogen bonds is of specific interest because these play a crucial duty in all-natural items. For instance, amide bonds connect individual amino acids right into healthy proteins.
Although there has been some success in the functionalization of hefty hydrocarbons, even at the end placements, the particularly strong C-H bonds of light alkanes, predominantly methane, can rarely be divided in all. Making use of these critical components of natural gas as the artificial foundation is specifically preferable, as it would undoubtedly allow for making use of this frequently lost side-product of oil removal.
A group led by Ana Caballero and also Pedro J. Pérez (Universidad de Huelva, Spain), along with John F. Hartwig (University of California, Berkeley, U.S.), has currently efficiently paired amides (nitrogen-containing natural compounds) to light alkanes with loss of a hydrogen atom. The products of these dehydrogenative amidations are called N-alkyl amides.
The starting factor for this approach was the amidation of C-H bonds in hefty alkanes with a copper-based catalyst and di-tert-butyl peroxide as an oxidizing representative, as established numerous years earlier by the Hartwig team. The variant of the catalyst led to success. Suppose the copper has phenanthroline-type ligands (an aromatic, nitrogen-containing system of three six-membered rings). In that case, it is feasible to create high yields in the response of ethane with benzamide – along with a variety of other amides – using benzene as a solvent. The answer also worked when supercritical carbon dioxide – a more eco-friendly alternative – was used as a solvent. The reaction with ethane is an unusual C-N bond development with a non-activated primary C-H bond.
Lp, n-butane, as well as iso-butane offered comparable outcomes. In the light alkanes, sensitivity is associated considerably more strongly with the dissociation energy of the C-H bonds than in greater alkanes.
And also methane? Even the most complex candidate – amidation of methane has never formerly been observed – could be coupled to the amide. Isotopic experiments were made use of to verify that methane reacts to develop N-methylbenzamide.
Reference: M. Ángeles Fuentes et al, Copper‐Catalyzed Dehydrogenative Amidation of Light Alkanes, Angewandte Chemie International Edition (2021). DOI: 10.1002/anie.202104737
