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 connected 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 adhered hydrogen atoms. In the journal Angewandte Chemie, a group of scientists has currently defined precisely how they split these bonds while forming brand-new carbon-nitrogen bonds (amidation).

If it were possible to split the C-H bonds in hydrocarbons easily, it would certainly be feasible to synthesize complex organic molecules, such as pharmaceuticals, far more conveniently and directly from petroleum. 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 part in natural products. For instance, amide bonds connect individual amino acids with proteins.

Despite some achieved success in the functionalization of heavy hydrocarbons, even at the end placements, the powerful C-H bonds of light alkanes, predominantly methane, can rarely be divided. Using these primary components of natural gas as the synthetic building blocks is preferable, as it would undoubtedly allow for using this frequently lost side-product of petroleum extraction.

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 successfully 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 beginning of 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 agent, as elaborated 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 reaction 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.

Propane, n-butane, as well as iso-butane offered comparable outcomes. In the light alkanes, reactivity associates considerably more strongly with the dissociation energy of the C-H bonds than in higher alkanes.

And also methane? Even the most complex candidate – amidation of methane has never been observed – could be coupled to the amide. Isotopic experiments were utilized to verify that methane reacts to the formation of N-methylbenzamide.

Originally published on Laboratory Equipment. Read the original article.

Reference: M. Ángeles Fuentes et al, Copper‐Catalyzed Dehydrogenative Amidation of Light Alkanes, Angewandte Chemie International Edition (2021). DOI: 10.1002/anie.202104737