Elucidation of Reaction Mechanisms in Organic Chemistry (overall)
Identification of Products and Intermediates - Introduction
The starting products, products and intermediates are the most important cornerstones of a reaction mechanism. They form the basic framework of a mechanism. The identification of the starting products is rather trivial. This is usually true in the case of organic syntheses, as the starting products are given by the chemist. However, in the case of biochemical reaction mechanisms (click here for a beautiful example with 3D molecular animations), the starting products are given by nature. Therefore, it is not trivial but rather often very difficult for the biochemist to identify the enzymes, , solvent molecules (water), reduction equivalents (e.g. NADH) or energy suppliers (e.g. ATP) involved in the biochemical reaction. This section is restricted to organic syntheses.
Before attempting to explain the methods of identification of products and intermediates, the terms product and intermediate (product) must first be defined. In the course of the reaction along the reaction coordinate, the energy of the reactants changes depending on the extent to which bonds are expanded or broken, bond angles are deformed, or steric and electronic interactions appear at the respective point of the reaction coordinate. The change of energy along the reaction coordinate can be illustrated by the following diagram:
In the most elementary case, only one energy maximum is passed through on the course from the starting products to the products. If two or more local energy maxima are crossed, one or more local energy minima inevitably exist between these maxima. The structures of the reactants at such local energy minima represent the intermediates. Due to the sufficiently low activation energy , the intermediates are converted into the products (P). Under the reaction conditions, a further reaction of the products is impossible. The activation energy of all additionally conceivable conversions of the products such as, for example, the combustion, that is the complete oxidation by oxygen, is too high. Therefore, virtually no further reaction can occur. However, in equilibrium reactions the products can still be reconverted into the intermediates, or even into the starting products. Thus, the products represent the final point of the reaction coordinate.
The reaction rate of the conversion of the intermediates into the products (or back into the starting products) increases with the decrease in the activation energy of the respective step. That is, the deeper the valley between the energy maxima, the slower the accompanying intermediates are converted into the products, and the higher is the mean lifetime of the intermediates ( is related to the rate constant k of a reaction by the . In the most elementary case of a one-step reaction, the Arrhenius equation is: ln k = - / RT + ln A).
The concentration of an intermediate during a reaction depends, on the one hand, on the mean lifetime of the intermediate and, on the other hand, on the reaction rate at which the intermediate is formed from the starting products (in case of equilibrium reactions, it also depends on the reaction rate at which the intermediate is formed from the products). With a high formation rate and a high mean lifetime of the intermediate, a considerable concentration of the intermediate can occur.
These criteria considerably influence the practice of identification of the products and intermediates. The products are usually stable (very high mean lifetime), appear in a high concentration (at the end of the reaction), and they can usually be isolated as pure substances. In contrast, the intermediates are merely metastable. They are characteristic of a very short mean lifetime and a low concentration. Additionally, they virtually never occur at the end of the reaction, apart from equilibrium reactions, and they can rarely be isolated.
Therefore, the analytical methods that are applied in order to identify intermediates are often quite different from the methods of identifying products.