Physical organic chemistry

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A branch of science concerned with the scope and limitations of the various rules, effects, and generalizations in use in organic chemistry by means of physical and mathematical methods. It includes, but is not limited to, the dynamics and energetics of organic chemical transformations, transient intermediates in these reactions, rate comparisons between families of reactions, dynamic stereochemistry, conservation of orbital symmetry, the least-motion principle, the isomer number for a given elemental composition, conformational analysis, nonexistent compounds, aromaticity, tautomerism, strain and steric hindrance, and the double-bond rule. Spectroscopy is the main tool employed, with nuclear magnetic resonance being the most widely used spectroscopic technique. With the advent of modern fast computers, computational chemistry has also become an important tool. See also Nuclear magnetic resonance (NMR); Spectroscopy.

Physical organic chemistry is traditionally distinguished from, yet totally intertwined with, synthetic organic chemistry, which deals with the question of how to obtain desired products from available compounds. This distinction can be illustrated with a diagram (see illustration) showing how the energy might vary during a chemical reaction in which the reactant R yields a product P (R → P). Whereas the synthetic organic chemist will be interested primarily in the practical problem of how to convert R into P, the physical organic chemist studies the curve or curves connecting R and P as well as the structure and physical properties at all extrema, including R and P. However, the demarcation between synthetic organic chemistry and physical organic chemistry is not sharp. Physical organic chemists have contributed greatly to the understanding of the chemistry of hydrocarbons and their derivatives and have enhanced the repertoire of the synthetic organic chemists. In turn, synthetic organic chemists have made possible the construction of the custom-made, often intricate molecules that physical organic chemists use for their studies. The efforts of both groups, moreover, have made possible the birth of such new fields as molecular biochemistry and computational chemistry. See also Computational chemistry.

Energy profile of an organic reaction R → P. T terms indicate transition states and I terms indicate intermediates.

Chemical reaction mechanisms

The diagram shown in the illustration is also useful in discussions of the dynamics of chemical reactions. It is an attempt to portray how the atoms in the reactant molecule R may move in space to their final positions in the product molecule P, and how the potential energy of the system would vary as a function of these positions. A complete correlation would be multidimensional; what is normally shown is a cross section in which the maximum potential energy is in fact a minimum (saddle point). While an essentially infinite number of pathways between R and P can be imagined and followed, the vast majority of the molecules will in practice use the one that makes the least demand on energy to reach the next maximum; this pathway is known as the reaction mechanism. The maxima (T terms in the illustration) are known as transition states, and the minima (I terms in the illustration) as intermediates.

If a reaction has a single transition state (and, hence, no intermediate), it is known as concerted; alternatively, it is step-wise. A stepwise reaction is simply a succession of concerted steps in which the intermediates are not isolated. See also Free radical; Organic reaction mechanism; Reactive intermediates; Photochemistry.

Chemical kinetics

The most important route to quantitative information about a reaction is the study of its kinetics. This must begin with an experimental determination of the rate law: the expression that shows how the rate of formation of product d[P]/dt (or loss of reactant: −d[R]/dt) depends on the concentration of all species involved in the reaction other than the solvent. The differential might be found to equal k[R₁], k[R₁] [R₂], k[R₁]², and so on; k is known as the rate constant, and the reaction is described as first-order, second-order, and so forth, depending on the total number of concentration terms. One important feature is that the reaction order equals the sum of all molecules that have participated in the formation of the transition state (T₂ in the illustration). Thus, for a reaction to be concerted, it is necessary that the order equal the sum of all reactant molecules involved in the stoichiometry. See also Catalysis; Chemical dynamics.

Stereochemistry

This is also a powerful tool in physical organic chemistry. Experimental work has demonstrated that when a chiral compound such as (−)HCR₁R₂X is converted into optically active HCR₁R₂Y by direct displacement with Y, the product obtained has an optical rotation that is opposite to that exhibited by the same material if it is produced in two steps, via initial displacement by A to give intermediate HCR₁R₂A as shown in the reaction scheme below. This result demonstrates that displacement reactions occur with inversion; the reagent approaches in front, and the leaving group departs in the back.

Isomers

The isomer number has perhaps been the most important organizing principle in organic chemistry since its inception. Simply put, it means that for every elemental composition and molecular mass the isomer number can be predicted by writing all possible sequences of the atoms present, obeying the valence numbers of the atoms: four for carbon, three for nitrogen, two for oxygen, one for hydrogen and the halogens, and so forth. Once reliable atomic weights became available so that elemental compositions could be reported with confidence, this simple rule proved remarkably successful. See also Chemical bonding; Organic chemistry; Valence.

The need to specify molecular mass has proved more troublesome: it requires a definition of the concept of a molecule. Such definitions usually refer to covalent bonds as the entities that hold the atoms together, to rule out ionic species such as sodium chloride as candidates.

Among the extra compounds, none have affected organic chemistry more drastically than the stereoisomers. It turns out that for all but the simplest compounds a given sequence of the atoms may represent two, more than two, or even many more isomers. See also Conformational analysis; Molecular isomerism.

Many compounds that are considered to be nonexistent, even though they are allowed by the simple rules of isomer numbers, in fact are transient intermediates in various reactions. Sometimes they can be detected spectroscopically, but cannot be isolated. There are instances in which neither of two isomers can be isolated, but mixtures of the two can. In other words, the barrier between the two is low, and the equilibrium constant is close to unity. An example is acetoacetic ester, which normally contains about 15% of the enol isomer. Such isomers are known as tautomers.