RUDN University chemist showed that water plays a crucial role in the mechanism of the Henry reaction catalyzed by new copper complexes

RUDN University chemist showed that water plays a crucial role in the mechanism of the Henry reaction catalyzed by new copper complexes

A RUDN University chemist revised the mechanism of the Henry reaction catalyzed by copper(II) complexes. Thus, using new copper(II) complexes (obtained in the same laboratory), he showed that water plays a crucial role in the asymmetric Henry reaction, directly participating in the catalytic cycle of the reaction. Previously, this factor was never taken into account, and all scientists thought that the copper(II) complex works as a classical Lewis acid.

In fact, it turned out that the copper complex in coordination with the water molecule activates it, turning it into Bronsted acid, and thus the water activates the original aldehyde. The data obtained from the experiment allow us to understand the mechanism of the Henry reaction and will help in the creation of the most important classes of substances for the pharmaceutical industry: α-nitroketones, ketones, nitroalkenes and β-amino alcohols. 

Asymmetric Henry reaction, allowing the synthesis of valuable organic molecules, was first conducted by Japanese chemist Masakatsu Shibasaki in 1992. He was able to conduct a reaction with high enantioselectivity, using catalysts based on copper complexes. However, before this work, there were still questions about the mechanism of this reaction. Vladimir Larionov, an employee of the Department of Inorganic Chemistry of RUDN University, Ph.D. in Chemistry, using new copper(II) complexes showed that the water molecule plays a crucial role in the Henry reaction and is directly involved in the catalytic cycle. Previously, scientists did not pay much attention to this, but only stated the fact that the reaction rate increases by several orders with the participation of water.

These complexes can be used to produce precursors of drugs such as (S)-propranolol (β-blocker), ®-norepinephrine and ®-salbutamol (β-receptor agonists), amprenavir-Vertex 478 (HIV protease inhibitor) and L-acosamine (class of anthracycline antibiotics).

It was known from previous studies that the asymmetric Henry reaction is better performed in aqueous and alcoholic solvents. Therefore, the authors of the study tested the reaction in solvents (methanol, aldehyde-nitromethane-water) with two catalytic systems — cobalt (III) and copper(II) complexes. In the case of the cobalt complex, the metal ion did not participate in the reaction, and the copper ion could coordinate the water molecule (or molecules). The reaction was faster with the copper complex, and chemists obtained several necessary types of chemicals (ligands and nitrated alcohol). Cobalt catalyst functioned worse, especially in the production of nitrated alcohol. That is why the authors decided to focus on the copper catalyst.

However, the use of a copper catalyst in methanol also caused problems. The formation of nitrated alcohol only of the racemic form was observed during the condensation. In this case, the reaction rate did not slow down, and blocking of the catalytic center of the copper ion did not occur. Calculations have shown that water forms a strong bond between the copper center and the carbonyl group. The reaction was completed within 1 hour, and the yield of nitrated alcohol reached 61%. At the same time, nitrated alcohol was displaced by water and did not block the catalytic center of the copper complex. Thus, contrary to previous ideas, it was

Chemists concluded that the effectiveness of previously studied chiral catalysts based on copper (II) was underestimated because the water (or alcohol) content of the reaction was not taken into account and was not evaluated. This research will open the way to study the Henry reaction mechanism and to create the new catalytic systems based on copper complexes.

The results are published in the international American journal Inorganic Chemistry.

News
All news
Science
22 Oct
A Chemist from RUDN University Developed a New Method for Combating Antibiotic Resistance in Microbes

Bacteria in biofilms are 1,000 times more resistant to antibiotics, disinfectants, mechanical treatment, and other types of stress. A chemist from RUDN University suggested a method to prevent the formation of biofilms and reduce the resistance of bacteria to antimicrobial medications. This might help increase the efficiency of antibacterial treatment in the food industry, medicine, and agriculture.

Science
20 Oct
RUDN University Professor Suggested how to Clean Up Space Debris

A specialist in spacecraft movement control analyzed the process of placing vehicle stages, boosters, and other space debris into the so-called disposal orbit and suggested cleaning lower orbits up with a spacecraft that has modules with engine units on board. These modules will attach to space debris objects and move them away. As for the geostationary orbit, a preferable way to clean it up would be a towing spacecraft that transports space debris objects into the disposal orbit.

Science
14 Oct
A Biologist from RUDN University Found Sex Differences in Inflammatory Reactions in Rat Pups

A biologist from RUDN University studied the development of the immune response in prepubertal male and female animals. According to her, the severity and mortality of infectious and inflammatory diseases at this age depend not on the sex hormones, but mainly on the chromosome set or karyotype.