Predicting Organic Reactivity

A mechanism describes, as a function of time, the chemical steps necessary for one molecule to be transformed into another. It gives the interrelationships among the molecules whose motions and collisions are necessary for the chemical transformation. Specifically, it provides the relative positions and energies of all nuclei and electrons in the reactants, intermediates, activated complexes, and products, as well as tho.se of the solvent, at each stage of the transformation. Gould likened the mechanism to a motion picture of the chemical transformation. By analyzing each frame of the motion picture individually, we can analyze each step of the reaction in a sequential manner. 

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Socorro IM, Goodman JM (2006) The ROBIA program for predicting organic reactivity. J Chem Inf Model 46(2) 606-614 http //www.reaxys.com. Accessed 17 Oct 2013... 

The fonn of the classical (equation C3.2.11) or semiclassical (equation C3.2.11) rate equations are energy gap laws . That is, the equations reflect a free energy dependent rate. In contrast with many physical organic reactivity indices, these rates are predicted to increase as -AG grows, and then to drop when -AG exceeds a critical value. In the classical limit, log(/cg.j.) has a parabolic dependence on -AG. Wlren high-frequency chemical bond vibrations couple to the ET process, the dependence on -AG becomes asymmetrical, as mentioned above. 

Addy Press s book, Theoretical and Physical Principles of Organic Reactivity, Wiley, New York, 1995, is an invaluable tool for understanding the way constructing a reaction profile can help the physical chemist to predict the outcome of a chemical reaction. Lowry and Richardson s Mechanism and Theory in Organic Chemistry (above) is also germane. 

The introduction of a substituent in an organic compound may affect its reactivity in a given reaction. A number of quantitative relationships have been suggested in connection with the effect of substituents on the rate constant of the reaction. Such structure-reactivity co-relations are helpful in predicting the reactivity of organic compounds in various reactions and also in verifying the reaction mechanism. One such useful relationship was proposed by Hemmett, which relates the equilibrium and rate constants for the reaction of meta and para substituted benzene derivatives. 

To summarize, there is still a need for carefully determining more rate constants for various substances of biological interest in their various charged forms. This phase of the subject will be complete when critically chosen values have passed into the Tables and when theoretical correlations have been sufficiently developed to enable rate constants for unexamined substances to be reliably predicted. There is also still a need to correlate the reactivity of the hydrated electron with the reactivity of free radicals such as H, OH, organic radicals, peroxy radicals, etc., so as to be able to predict the reactivity of unexamined free radicals. Another need is to establish the influence of conditions on the rate constants. The influence of ionic strength is now well known, but other factors, such as the dielectric properties of the medium, have been shown to have an effect in some cases (2, 20). Also, the effect of temperature has been investigated in only a few cases (9). 

This book will be particularly valuable to all investigators working with complex organic molecules, whether they be synthetic, medicinal or bioorganic chemists, since it will provide a timely view of stereoelectronic effects and how they may be applied, both to rationalise and to predict organic chemical reactivity. 

Problems 1-3 emphasize the three dimensional representation of various cyclic molecules and evaluation of their energies by the A, G, and U parameters. In Problems 4-6, we apply conformational analysis to predict the reactivity of carbocyclic systems toward various reagents and to gather information regarding the preferred stereochemical course of the corresponding reactions. Further examples of applications of conformational analysis in organic synthesis are incorporated in Problems 7-9. 

One approach of use in ground state organic chemistry is a static one. This assumes that one can predict the reactivity of a molecule from a description of the starting material itself. Thus, very electron rich centers are subject to electrophilic attack, electron poor sites in the molecules are expected to be susceptible to facile nucleophilic attack, weak bonds are subject to scission, etc. This approach is imperfect, in that a reaction course is really determined by a preference for the lowest energy transition state. Nevertheless, this starting state reasoning is quite useful, since most often it is, indeed, the predicted site of attack which affords the preferred transition state. 

As mentioned at the end of Chapter 1, an understanding of heterolytic reaction mechanisms must be accompanied by an understanding of the properties of organic acids and bases. Through this understanding, an ability to predict the reactive species in organic reactions and the reactive sites in organic molecules will evolve. Therefore, this chapter focuses on the properties of acids, dissociation constants, and the relative acidities observed for protons in different environments. 

Thomson Click Organic interactive to learn to draw the structures of carbonyl enolates and predict their reactivity. 

An understanding of interaction diagrams is not absolutely necessary for using the principle of electron flow to predict organic reaction products. However, it is useful for understanding reactivity trends and the stability of reactive intermediates. This section relies on the principles discussed in Section 1.6, An Orbital View of Bonding. 

This section is intended to provide the organic chemist with relatively simple guidelines, rational structure reactivity relationships and rules-of-thumb to predict the reactivity of biradicals and their response to changes in manageable parameters such as temperature, solvent polarity and magnetic fields. The same considerations hold, mutatis mutandis, for carbenes and nitrenes. 

It is difficult, if not impossible, to predict the reactivity of coal based on physical or chani-cal analyses, because coal is a complex mixture of macromolecules as well as a physical mixture of organic and inorganic constituents. Evidence can be accumulated to reason that reactions in the organic materials can be influenced by both clay minerals and pyrites found distributed within the organic coal matrices. One convenient basis for understanding the reactions in both systems is to examine reactive functional groups. 

CHEMICAL reactivity presents one of the great unsolved problems of organic chemistry. We know a great deal about how to approach the problem but are usually stymied by the fact that we always seem to have more parameters to fix than we have results to calculate. In this chapter we shall consider contributions of the LCAO method toward predicting relative reactivities of organic molecules. We shall be illustrative rather than comprehensive, and many excellent treatments will necessarily have to be omitted to keep the discussion within reasonable bounds. Fortunately, a number of comprehensive reviews on the subject are available. 

HOMO and LUMO, as particularly important MOs to predict the reactivities in many types of reaction. They also postulated that the electron delocalization or transfer between the reagent and reactant in the vicinity of the transition state is essential in determining the reactivity of organic compounds and the frontier orbitals play a most important role in such an electron delocalization. 

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