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.

Visiting Professors View all
03 Nov 2017
Michele Pagano is a graduate of the University of Pisa, a leading scientist, the author of more than 200 publications in international journals, and a participant in many international research projects
International Projects View all
Similar newsletter View all
22 Oct
RUDN chemist creates catalyst to produce anti-mosquito substances

A chemist from RUDN University has developed a catalyst for the production of eugenol acetate, a substance that destroys the larvae of mosquitoes transmitting dangerous diseases, being a safe chemical for human health.

22 Oct
RUDN soil scientists developed a new method for assessing soil fertility

RUDN soil scientists have revealed a direct correlation between the rate of soil formation of carbon dioxide, called CO2 emissions, and the content of microbial biomass in it. It is known that CO2 emission from soil is mainly conditioned by respiration of soil microorganisms and plant roots. The more CO2 soil emits, the more microbial biomass it usually contains. It was shown that CO2 emission by chernozem of different ecosystems (or different types of land use) correlates with the content of microbial biomass, and most closely with the rate of its microbial respiration. And the soil with good microbial properties has the “best quality”, is more fertile, provides the highest yield of crops and other plant biomass.

22 Oct
RUDN University chemists proposed a way to reduce three times the temperature for the oxidation of alkanes

RUDN University chemists and their colleagues from the Russian Academy of Sciences have proposed new catalysts that allow to reduce the temperature of the oxidation reaction of alkanes three times — from 150 to 50 degrees. This significantly reduces the cost of synthesizing alcohols, aldehydes and other compounds needed, in particular, for the production of nylon and capron.

Similar newsletter View all