More O'Ferrall–Jencks plot

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More O’Ferrall–Jencks plots are two-dimensional representations of multiple reaction coordinate potential energy surfaces for chemical reactions that involve simultaneous changes in two bonds. As such, they are a useful tool to explain or predict how changes in the reactants or reaction conditions can affect the position and geometry of the transition state of a reaction for which there are possible competing pathways. [1]

Reaction coordinate

In chemistry, a reaction coordinate is an abstract one-dimensional coordinate which represents progress along a reaction pathway. It is usually a geometric parameter that changes during the conversion of one or more molecular entities. In molecular dynamics simulations, a reaction coordinate is called collective variable.

Potential energy surface

A potential energy surface (PES) describes the energy of a system, especially a collection of atoms, in terms of certain parameters, normally the positions of the atoms. The surface might define the energy as a function of one or more coordinates; if there is only one coordinate, the surface is called a potential energy curve or energy profile. An example is the Morse/Long-range potential.

Chemical reaction Process that results in the interconversion of chemical species

A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking of chemical bonds between atoms, with no change to the nuclei, and can often be described by a chemical equation. Nuclear chemistry is a sub-discipline of chemistry that involves the chemical reactions of unstable and radioactive elements where both electronic and nuclear changes can occur.

Contents

Brief history

These plots were first introduced by R. A. More O’Ferrall to discuss mechanisms of β-eliminations [2] and later adopted by W. P. Jencks in an attempt to clarify the finer details involved in the general acid-base catalysis of reversible addition reactions to carbon electrophiles such as the hydration of carbonyls. [3]

In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.

Elimination reaction type of organic reaction in which two substituents are removed from a molecule in either a one or two-step mechanism

An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one or two-step mechanism. The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 reaction. The numbers do not have to do with the number of steps in the mechanism, but rather the kinetics of the reaction, bimolecular and unimolecular respectively. In cases where the molecule is able to stabilize an anion but possesses a poor leaving group, a third type of reaction, E1CB, exists. Finally, the pyrolysis of xanthate and acetate esters proceed through an "internal" elimination mechanism, the Ei mechanism.

In organic chemistry, a nucleophilic addition reaction is an addition reaction where a chemical compound with an electron-deficient or electrophilic double or triple bond, a π bond, reacts with electron-rich reactant, termed a nucleophile, with disappearance of the double bond and creation of two new single, or σ, bonds. The reactions are involved in the biological synthesis of compounds in the metabolism of every living organism, and are used by chemists in academia and industries such as pharmaceuticals to prepare most new complex organic chemicals, and so are central to organic chemistry. Addition reactions require the presence of groups with multiple bonds in the electrophile(due to the fact that double bonds and even triple bonds can both lack electron rich sources): carbon–heteroatom multiple bonds as in carbonyls, imines, and nitriles, or carbon–carbon double or triple bonds. The lack of electron rich sources is due to the fact that these bonds are partially empty, even though they remain connected, since the region occupying the orbital is essentially dead. This electrophilic behavior is defined as empty space since everything inside is basically without any source of electricity except from outside the bond, since bonds tend to want to attract more to themselves(whether this be electric or non-electric can differ in most situations). The addition of the nucleophile means the continuous addition of a negative charge throughout the reaction, unless an electrophile also makes itself present to form a complete structure with no charge at all. The negative charge being continuous throughout the reaction until the formation of an intermediate, bearing the charge, thus is the addition reaction we have before us. Once this meets an electrophile, then the intermediate formed with the negative charge can thus be neutralized to form a complete structure via a type of bond.

Description

Figure 1. A generic More O'Ferrall-Jencks plot. R, I(1), I(2) and P stand for reactant(s), intermediate(S) 1, intermediate(s) 2 and product(s) respectively. The thick arrows represent movement of the transtitions state (black dot) parallel and perpendicular to the diagonal (red line). The thin arrow is the vector sum of the thick arrows. Generic2.JPG
Figure 1. A generic More O’Ferrall–Jencks plot. R, I(1), I(2) and P stand for reactant(s), intermediate(S) 1, intermediate(s) 2 and product(s) respectively. The thick arrows represent movement of the transtitions state (black dot) parallel and perpendicular to the diagonal (red line). The thin arrow is the vector sum of the thick arrows.

In this type of plot (Figure 1), each axis represents a unique reaction coordinate, the corners represent local minima along the potential surface such as reactants, products or intermediates and the energy axis projects vertically out of the page. Changing a single reaction parameter can change the height of one or more of the corners of the plot. These changes are transmitted across the surface such that the position of the transition state (the saddle point) is altered. [1]

Consider a generic example in which the initial transition state along a concerted pathway is represented by a black dot on a red diagonal (Figure 1). Changing the height of the corners can have two effects on the position of the transition state: it can move along the diagonal, reflecting a change in the Gibbs free energy of the reaction (ΔG°), or perpendicular to it, reflecting a change in the energy of competing pathways. Thus, in accordance with the Hammond postulate, the transition state moves along the diagonal towards the corner that is raised in energy (a Hammond effect) and perpendicular to the diagonal towards the corner that is lowered (an anti-Hammond effect). [1] [4] In this example, R is raised in energy and I(2) is lowered in energy. The transition state moves accordingly and the vector sum of both movements gives the real change in its position.

Gibbs free energy gibbs energy of formation

In thermodynamics, the Gibbs free energy is a thermodynamic potential that can be used to calculate the maximum of reversible work that may be performed by a thermodynamic system at a constant temperature and pressure. The Gibbs free energy is the maximum amount of non-expansion work that can be extracted from a thermodynamically closed system ; this maximum can be attained only in a completely reversible process. When a system transforms reversibly from an initial state to a final state, the decrease in Gibbs free energy equals the work done by the system to its surroundings, minus the work of the pressure forces.

Applications

Elimination reactions

Figure 2. More O'Ferrall-Jencks plot of the competing b-elimination mechanisms: E2, E1 and E1cB. The arrows indicate the effects of increasing the leaving group ability on the position of the transition state. Elimination2.JPG
Figure 2. More O’Ferrall–Jencks plot of the competing β-elimination mechanisms: E2, E1 and E1cB. The arrows indicate the effects of increasing the leaving group ability on the position of the transition state.

Initially, More O’Ferrall introduced this type of analysis to discuss the continuity between concerted and step-wise β-elimination reaction mechanisms. The model also provided a framework within which to explain the effects of substituents and reaction conditions on the mechanism. [2] The appropriate lower energy species were placed at the corners of the two dimensional plot (Figure 2). These were the reactants (top left), the products (bottom right) and the intermediates of the two possible stepwise reactions: the carbocation for E1 (bottom left) and the carbanion for E1cB (top-right). Thus, the horizontal axes represent the extent of deprotonation (C-H bond distance) and the vertical axes represent the extent of leaving group departure (C-LG distance). By applying the Hammond and anti-Hammond effects, [4] he predicted the effects of various changes in the reactants or reaction conditions. For example, the effects of introducing a better leaving group on a substrate that initially eliminates via an E2 mechanism are illustrated in Figure 2. A better leaving group increases the energy of the reactants and of the carbanion intermediate. Thus, the transition state moves towards the reactants and away from the carbanion intermediate.

Carbocation cation containing an even number of electrons with a significant portion of the excess positive charge located on one or more carbon atoms

A carbocation is an ion with a positively charged carbon atom. Among the simplest examples are the methenium CH+
3, methanium CH+
5 and vinyl C
2H+
3 cations. Occasionally, carbocations that bear more than one positively charged carbon atom are also encountered.

A carbanion is an anion in which carbon is trivalent (forms three bonds) and bears a formal negative charge in at least one significant mesomeric contributor (resonance form). Absent π delocalization, carbanions assume a trigonal pyramidal, bent, or linear geometry when the carbanionic carbon is bound to three (e.g., methyl anion), two (e.g., phenyl anion), or one (e.g., acetylide anion) substituents, respectively. Formally, a carbanion is the conjugate base of a carbon acid:

In chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules, but in either case it is crucial that the leaving group be able to stabilize the additional electron density that results from bond heterolysis. Common anionic leaving groups are halides such as Cl−, Br−, and I−, and sulfonate esters such as tosylate (TsO−). Fluoride (F−) functions as a leaving group in the nerve-agent sarin gas. Common neutral molecule leaving groups are water and ammonia. Leaving groups may also be positively charged cations (such as H+ released during the nitration of benzene); these are also known specifically as electrofuges.

Figure 3. More O'Ferrall-Jencks plot of competing nucleophilic aliphatic substitution mechanisms: SN1 and SN2. The arrows represent the effect of increasing the nucleophilicity of the nucleophile on the position of the transition state. Substitution2.JPG
Figure 3. More O’Ferrall–Jencks plot of competing nucleophilic aliphatic substitution mechanisms: SN1 and SN2. The arrows represent the effect of increasing the nucleophilicity of the nucleophile on the position of the transition state.

Interestingly, the model does not predict any change in leaving group departure at the transition state. Instead the extent of deprotonation is expected to decrease. This can be explained by the fact that a better leaving group needs less assistance from a developing neighbouring negative charge in order to depart. The true change predicts more carbocation character at the transition state and a mechanism that is more E1-like. These observations can be correlated with Hammett ρ-values. [5] Poor leaving groups correlate with large positive ρ-values. Gradually increasing the leaving group ability decreases the ρ-value until it becomes large and negative, indicating the development of positive charge in the transition state.

Substitution reactions

A similar analysis, done by J. M. Harris, has been applied to the competing SN1 and SN2 nucleophilic aliphatic substitution pathways. [6] The effects of increasing the nucleophilicity of the nucleophile are shown as an example in Figure 3. An agreement with Hammet ρ-values is also apparent in this application. [7]

Addition to carbonyls

Figure 4. More O'Ferrall-Jencks plot of acid-catalyzed versus uncatalyzed nucleophilic addition to a carbonyl. The arrows represent the effects of increasing the strength of the acid on the position of the transition state. Addition.JPG
Figure 4. More O’Ferrall–Jencks plot of acid-catalyzed versus uncatalyzed nucleophilic addition to a carbonyl. The arrows represent the effects of increasing the strength of the acid on the position of the transition state.

Finally, this type of plot can readily be drawn to illustrate the effects of changing parameters in the acid-catalyzed nucleophilic addition to carbonyls. The example in Figure 4 demonstrates the effects of increasing the strength of the acid. In this case, the extent of protonation is the α-value in the Brønsted catalysis equation. The fact that the α-value remains unchanged explains the linearity of Brønsted plots for such a reaction. [8]

Ultimately, the More O’Ferrall–Jencks plots have qualitative predictive and explanatory power regarding the effects of changing substituents and reaction conditions for a wide variety of reactions.

See also

Related Research Articles

Catalysis chemical process

Catalysis is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst, which is not consumed in the catalyzed reaction and can continue to act repeatedly. Because of this, only very small amounts of catalyst are required to alter the reaction rate in principle.

Transition state set of states (each characterized by its own geometry, energy) in which an assembly of atoms, when randomly placed there, would have an equal probability of forming the reactants or of forming the products of that elementary reaction

The transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. At this point, assuming a perfectly irreversible reaction, colliding reactant molecules always go on to form products. It is often marked with the double dagger ‡ symbol.

In chemistry, a reactive intermediate or an intermediate is a short-lived, high-energy, highly reactive molecule. When generated in a chemical reaction, it will quickly convert into a more stable molecule. Only in exceptional cases can these compounds be isolated and stored, e.g. low temperatures, matrix isolation. When their existence is indicated, reactive intermediates can help explain how a chemical reaction takes place.

The Brønsted catalysis equation or law of correlation, after Johannes Nicolaus Brønsted, gives the relationship between acid strength and catalytic activity in general acid catalysis.

Nucleophilic aromatic substitution

A nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. There are 6 nucleophilic substitution mechanisms encountered with aromatic systems:

Hammonds postulate

Hammond's postulate, is a hypothesis in physical organic chemistry which describes the geometric structure of the transition state in an organic chemical reaction. First proposed by George Hammond in 1955, the postulate states that:

If two states, as, for example, a transition state and an unstable intermediate, occur consecutively during a reaction process and have nearly the same energy content, their interconversion will involve only a small reorganization of the molecular structures.

The Hammett equation in organic chemistry describes a linear free-energy relationship relating reaction rates and equilibrium constants for many reactions involving benzoic acid derivatives with meta- and para-substituents to each other with just two parameters: a substituent constant and a reaction constant. This equation was developed and published by Louis Plack Hammett in 1937 as a follow-up to qualitative observations in a 1935 publication.

The alpha effect refers to the increased nucleophilicity of an atom due to the presence of an adjacent (alpha) atom with lone pair electrons. This first atom does not necessarily exhibit increased basicity compared with a similar atom without an adjacent electron donating atom. The effect is well established with many theories to explain the effect but without a clear winner.

Enzyme catalysis catalysis of chemical reactions by specialized proteins known as enzymes

Enzyme catalysis is the increase in the rate of a chemical reaction by the active site of a protein. The protein catalyst (enzyme) may be part of a multi-subunit complex, and/or may transiently or permanently associate with a Cofactor. Catalysis of biochemical reactions in the cell is vital due to the very low reaction rates of the uncatalysed reactions at room temperature and pressure. A key driver of protein evolution is the optimization of such catalytic activities via protein dynamics.

Transition state theory scientific theory

Transition state theory (TST) explains the reaction rates of elementary chemical reactions. The theory assumes a special type of chemical equilibrium (quasi-equilibrium) between reactants and activated transition state complexes.

Physical organic chemistry, a term coined by Louis Hammett in 1940, refers to a discipline of organic chemistry that focuses on the relationship between chemical structures and reactivity, in particular, applying experimental tools of physical chemistry to the study of organic molecules. Specific focal points of study include the rates of organic reactions, the relative chemical stabilities of the starting materials, reactive intermediates, transition states, and products of chemical reactions, and non-covalent aspects of solvation and molecular interactions that influence chemical reactivity. Such studies provide theoretical and practical frameworks to understand how changes in structure in solution or solid-state contexts impact reaction mechanism and rate for each organic reaction of interest.

Energy profile (chemistry)

For a chemical reaction or process an energy profile is a theoretical representation of a single energetic pathway, along the reaction coordinate, as the reactants are transformed into products. Reaction coordinate diagrams are derived from the corresponding potential energy surface (PES), which are used in computational chemistry to model chemical reactions by relating the energy of a molecule(s) to its structure. The reaction coordinate is a parametric curve that follows the pathway of a reaction and indicates the progress of a reaction.

The Taft equation is a linear free energy relationship (LFER) used in physical organic chemistry in the study of reaction mechanisms and in the development of quantitative structure–activity relationships for organic compounds. It was developed by Robert W. Taft in 1952 as a modification to the Hammett equation. While the Hammett equation accounts for how field, inductive, and resonance effects influence reaction rates, the Taft equation also describes the steric effects of a substituent. The Taft equation is written as:

Enthalpy–entropy compensation is a specific example of the compensation effect. The compensation effect refers to the behavior of a series of closely related chemical reactions, which exhibit a linear relationship between one of the following kinetic or thermodynamic parameters for describing the reactions:

Nonclassical ion

Nonclassical carbocations are stabilized by charge delocalization from contributions of neighbouring C–C or C–H bonds, which can form bridged intermediates or transition states. Nonclassical ions have been extensively studied with the 2-norbornyl system, which as “naked” ion unambiguously exhibit such a bridged structure. The landmark of nonclassical ions are unexpectedly fast solvolysis rates and large differences between epimeric esters. Such behaviour is not restricted to 2-norbornyl esters, as has been shown with some cyclopentyl and steroidal esters with the tosyloxy leaving group.

George S. Hammond American chemist

George Simms Hammond was an American scientist and theoretical chemist who developed "Hammond's postulate", and fathered organic photochemistry,–the general theory of the geometric structure of the transition state in an organic chemical reaction. Hammond's research is also known for its influence on the philosophy of science. His research garnered him the Norris Award in 1968, the Priestley Medal in 1976, the National Medal of Science in 1994, and the Othmer Gold Medal in 2003. He served as the executive chairman of the Allied Chemical Corporation from 1979 to 1989.

In physical organic chemistry, the Grunwald–Winstein equation is a linear free energy relationship between relative rate constants and the ionizing power of various solvent systems, describing the effect of solvent as nucleophile on different substrates. The equation, which was developed by Ernest Grunwald and Saul Winstein in 1948, could be written

In chemistry, solvent effects are the influence of a solvent on chemical reactivity or molecular associations. Solvents can have an effect on solubility, stability and reaction rates and choosing the appropriate solvent allows for thermodynamic and kinetic control over a chemical reaction.

References

  1. 1 2 3 Anslyn, E. V., and Dougherty, D. A. Modern Physical Organic Chemistry. California: University Science Books, 2006, pp. 407–410.
  2. 1 2 More O’Ferrall, R. A. (1970). "Relationships between E2 and E1cB mechanisms of beta-elimination". J. Chem. Soc. B: 274–277. doi:10.1039/J29700000274.
  3. ↑ Jencks, William P. (1972). "General acid-base catalysis of complex reactions in water". Chemical Reviews. 72 (6): 705–718. doi:10.1021/cr60280a004.
  4. 1 2 Thornton, E. R. (1967) J. Am. Chem. Soc. 89, 2915
  5. ↑ Anslyn, E. V., and Dougherty, D. A. Modern Physical Organic Chemistry. California: University Science Books, 2006, pp. 586–588.
  6. ↑ Harris, J. Milton; Shafer, Steven G.; Moffatt, John R.; Becker, Allyn R. (1979). "Prediction of SN2 transition state variation by the use of More O'Ferrall plots". J. Am. Chem. Soc. 101 (12): 3295–3300. doi:10.1021/ja00506a026.
  7. ↑ Anslyn, E. V., and Dougherty, D. A. Modern Physical Organic Chemistry. California: University Science Books, 2006, p. 650.
  8. ↑ Anslyn, E. V., and Dougherty, D. A. Modern Physical Organic Chemistry. California: University Science Books, 2006, pp. 543–544.
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