A chemical intermediate is a molecular entity that forms during a chemical reaction, created from the initial reactants, and then reacts further to produce the final products. It is a temporary species that exists between the start and end of a reaction. This transient molecule is consumed in a subsequent step of the overall reaction.
The Role of Intermediates in Chemical Reactions
Many chemical reactions unfold through a series of individual steps, known as a reaction mechanism. Within this mechanism, an intermediate is a substance generated as a product in one elementary step that then acts as a reactant in a following step. Unlike initial starting materials or final products, intermediates are not present in the overall balanced chemical equation.
These intermediates are actual chemical species with a definite, though often very brief, existence. Their lifetime can range from picoseconds to several seconds, depending on their stability and reaction conditions. Intermediates influence the speed and direction a reaction takes, as their formation and subsequent reaction steps dictate the overall pathway.
Distinguishing Intermediates from Transition States
Chemical intermediates and transition states are distinct entities. An intermediate is a real molecule that occupies a “valley” or local minimum on a potential energy diagram. It exists for a measurable, albeit sometimes very short, period and could theoretically be isolated under specific conditions such as very low temperatures.
In contrast, a transition state is not a stable molecule but a fleeting, high-energy arrangement of atoms. It represents the peak of an energy barrier that molecules must overcome to transform from one state to another. A transition state has no measurable lifetime, existing only for the duration of a single molecular vibration.
On a reaction coordinate diagram, the x-axis illustrates the progress of the reaction, while the y-axis shows the potential energy; intermediates reside in energy dips, and transition states are at the energy peaks.
Key Types of Reactive Intermediates
Reactive intermediates are highly unstable and short-lived, playing a significant role in various chemical transformations.
Carbocations
Carbocations are one such type, characterized by a positively charged carbon atom that possesses only six valence electrons. This carbon atom is sp2 hybridized, resulting in a trigonal planar geometry, and it contains an empty p orbital that makes it electron-deficient and reactive as an electrophile. Carbocations form through the heterolytic cleavage of a covalent bond, where both bonding electrons leave with one atom, or by the addition of an electrophile to a pi bond.
Carbanions
Carbanions represent another class, featuring a negatively charged carbon atom that carries a lone pair of electrons. These species are electron-rich and behave as nucleophiles, readily donating electrons to form new carbon-carbon bonds. The stability of a carbanion is influenced by factors such as the inductive effect of adjacent electronegative atoms, the hybridization of the charged carbon, and the ability to delocalize the negative charge through resonance.
Free Radicals
Free radicals are highly reactive intermediates distinguished by having an unpaired electron on a carbon atom, giving them seven valence electrons. They are often formed through homolytic bond cleavage, where a covalent bond breaks such that each atom retains one of the bonding electrons. Like carbocations, free radicals are electron-deficient and tend to be stabilized by alkyl groups.
Carbenes
Carbenes are neutral carbon-based intermediates that possess two unshared valence electrons. The carbon atom in a carbene is covalently bonded to two other groups and has a total of six outer-shell electrons. Carbenes can exist in different electronic states, such as singlet or triplet. Due to their electron deficiency, carbenes are highly reactive and can act as either electrophiles or nucleophiles.
Intermediates in Biological and Industrial Processes
Intermediates are not confined to laboratory experiments; they are fundamental to processes in living organisms and large-scale industrial manufacturing.
Biological Processes
In biological systems, metabolic intermediates are compounds formed during biochemical reactions that convert initial substrates into final products, often for energy generation or biosynthesis. For example, the Krebs cycle, also known as the citric acid cycle, is a central pathway in cellular respiration. Here, compounds like citrate, isocitrate, alpha-ketoglutarate, succinate, fumarate, malate, and oxaloacetate are successively formed and consumed. These intermediates facilitate the oxidation of acetyl-CoA to produce carbon dioxide, generating energy carriers like NADH and FADH2, which are then used to synthesize ATP.
Industrial Processes
In industrial chemical synthesis, intermediates are crucial for efficiently producing a wide array of materials, including plastics, pharmaceuticals, and agricultural chemicals. These processes involve multiple steps where a stable intermediate might be synthesized, sometimes isolated, and then used as a starting material for a subsequent reaction. For instance, in the production of phenol and acetone, benzene and propylene are reacted to form cumene, which is then further processed. Similarly, alkyl chlorides serve as intermediates in the manufacture of various products. Utilizing intermediates allows for modular synthesis, enhancing overall yield and purity in large-scale production.