Chemists from Spain and the United States have come up with a new method for synthesizing macrocycles. They obtained them from covalent organic frameworks containing double bonds in their structure. The chemists broke these bonds using ozonolysis, and as a result, they obtained cycles of more than a hundred atoms. Previously, macrocycles of this type could not be obtained, the authors of the study write in the journal Science.
Macrocyclic molecules are typically prepared by macrocyclization reactions, in which a linear molecule is closed into a cycle. These reactions often have low yields because the molecules react more quickly with each other than with themselves. As a result, the reaction mixture must be highly diluted so that the molecules encounter each other less often, which slows the reaction rate.
A method for synthesizing macrocycles without using macrocyclization was proposed by chemists led by Jorge Albalad from the Autonomous University of Barcelona. Their idea was to first obtain covalent organic frameworks containing double bonds. And then break these bonds so that the desired macrocycles are released from the framework.
The researchers began by synthesizing a covalent organic framework from substituted stilbene with four amino groups and terephthalaldehyde. The two-dimensional structure of this framework was a kagome-type structure or a trihexagonal mosaic in which hexagonal and triangular pores alternate. Moreover, the double bonds in it were located in the triangular pores, and when they were broken, the hexagonal pores should not be damaged.
Next, the chemists oxidized all the imine groups in the framework to amide groups so that the imines would not be destroyed during ozonolysis, and then carried out the ozonolysis itself. The scientists bubbled ozone through a yellow suspension of the framework in a mixture of N,N-dimethylformamide, tetrahydrofuran, and methanol at -78 degrees Celsius for 10 minutes. After the reaction was complete, they obtained a colorless, transparent solution, to which they added dimethyl sulfide. As a result, all the carbon-carbon double bonds in the framework were destroyed, and in their place, each of the carbon atoms formed a double bond with oxygen.
As the chemists expected, the reaction product was a macrocycle, which they purified using size-exclusion chromatography and characterized using NMR spectroscopy and mass spectrometry. A similar framework, but with carboxyl groups instead of aldehydes, was obtained by the scientists when they used oxone instead of dimethyl sulfide in the second stage of the ozonolysis reaction. Both of the resulting macrocycles contained 114 atoms per cycle.
Thus, the chemists proposed a new approach to the synthesis of polyamide macrocycles. They managed to obtain several more products with 138 and 162 atoms in the cycle, as well as a polyimide macrocycle with 114 atoms in the cycle - and all this with practically quantitative yields and for gram loads of the starting materials.
Covalent organic frameworks are often used to absorb gases. For example, we recently reported on how chemists synthesized the first covalent organic framework capable of selectively absorbing up to two millimoles of carbon dioxide per gram of absorbent within an hour.