The most fundamental concepts in chemistry are structure, energetics, reactivity and their inter-relationships, which are indispensable for promoting chemistry into a rational science. In this regard, bond energy, the intrinsic determinant directly related to structure and reactivity, should be most essential in serving as a quantitative basis for the design and understanding of organic transformations. Although C-H activation/functionalization have drawn tremendous research attention and flourished during the past decades, understanding the governing rules of bond energetics in these processes is still fragmentary and seems applicable only to limited cases, such as metal-oxo-mediated hydrogen atom abstraction. Despite the complexity of C-H activation/functionalization and the difficulties in measuring bond energies both for the substrates and intermediates, this is definitely a very important issue that should be more generally contemplated. To this end, this review is rooted in the energetic aspects of C-H activation/functionalization, which were previously rarely discussed in detail. Starting with a concise but necessary introduction of various classical methods for measuring heterolytic and homolytic energies for C-H bonds, the present review provides examples that applied the concept and values of C-H bond energy in rationalizing the observations associated with reactivity and/or selectivity in C-H activation/functionalization.
Equilibrium acidity (pKa) scales of 15 substituted benzoic acids in four room temperature ionic liquids (RTILs), BmimOTf, BmimNTf2, BmpyNTf2, and Bm2imNTf2, were established under standard conditions using a modified indicator overlapping method. The effect of homo hydrogen bonding on equilibrium acidity was calibrated, and the derived pKa values were evidenced to be free from ion-paring complication. Regression analyses demonstrated that all of the pKa scales obtained in four RTILs are linearly correlated to each other with an R value better than 0.996. These scales are also correlated well with the pKa values in DMSO and with the corresponding gas-phase acidities with regression coefficients of 0.993 and 0.992, respectively. In addition, both the cation and anion of the ionic liquids were found to play a role in affecting the acidity of carboxylic acid.
Most organic transformation involves cleavage and formation of various covalent bonds, and naturally, can be regarded as a process of bond reorganization, which should be intrinsically related to bond energies (e.g., p K, BDE, etc.). However, in many cases such as in C-H bond activation/functionalization, direct correspondence between the bond energy and reaction rate or other relevant properties is only occasionally observed when applying the bond data by simple rules like the Linear Free-Energy Relationships (LFERs) in handling intricate reaction systems. In this Perspective, we present examples to argue that the above-mentioned situation is not a consequence of a diminishing role of the bond energetics in research, but most likely, comes from an improper use of energetic strategy, or simply due to a faulty selection of the data from unsuitable sources. Some advisable applications of bond energies in unscrambling the problems in modern day chemistry are exemplified through representative recent advances of the researches in this connection. Some of the possible directions of future research endeavors in the field of bond energetics and its prudent applications are recommended.
The acidity scale (∼14 p K units) of more than 90 triazolium, imidazolium, and imidazolinium based NHC precursors in DMSO was established systematically by a well-developed computational model. The substituent effects on the acidities of these NHC precursors were analyzed through acidity comparison and Hammett correlation. The binding energy (Δ G) of the reaction between NHC and CO was also calculated and linearly correlates with the basicity of the corresponding NHC, which implies that the stability of the NHC-CO adduct is essentially dictated by the basicity of NHC.
The rates of aromatic nucleophilic substitution reactions in liquid ammonia are much faster than those in protic solvents indicating that liquid ammonia behaves like a typical dipolar aprotic solvent in its solvent effects on organic reactions. Nitrofluorobenzenes (NFBs) readily undergo solvolysis in liquid ammonia and 2-nitrofluorobenzene is about 30 times more reactive than the 4-substituted isomer. Oxygen nucleophiles, such as alkoxide and phenoxide ions, readily displace fluorine of 4-NFB in liquid ammonia to give the corresponding substitution product with little or no competing solvolysis product. Using the pK(a) of the substituted phenols in liquid ammonia, the Brønsted β(nuc) for the reaction of 4-NFB with para-substituted phenoxides is 0.91, indicative of the removal of most of the negative charge on the oxygen anion and complete bond formation in the transition state and therefore suggests that the decomposition of the Meisenheimer σ-intermediate is rate limiting. The aminolysis of 4-NFB occurs without general base catalysis by the amine and the second-order rate constants generate a Brønsted β(nuc) of 0.36 using either the pK(a) of aminium ion in acetonitrile or in water, which is also interpreted in terms of rate limiting breakdown of the Meisenheimer σ-intermediate. Nitrobenzene and diazene are formed as unusual products from the reaction between sodium azide and 4-NFB, which may be due to the initially formed 4-nitroazidobenzene decomposing to give a nitrene intermediate, which may then give diazene or be trapped by ammonia to give the unstable hydrazine which then yields nitrobenzene.
A Brönsted basicity scale comprising nine representative N-heterocyclic olefins (NHOs) was established by measuring the equilibrium acidities of their corresponding precursors in DMSO using an ultraviolet–visible spectroscopic method. The basicities (pK aHs) of the investigated NHOs cover a range from 14.7 to 24.1. The basicities of unsaturated NHOs are stronger than those of their N-heterocyclic carbene (NHC) analogues; however, the basicities for the saturated ones are much weaker than those of their NHC analogues, which is largely due to the aromatization effect that intrinsically influences the acidic dissociations of NHC and NHO precursors. The nucleophilicities of four NHOs were measured photometrically by monitoring the kinetics of reactions of these NHOs with common reference electrophiles for quantifying nucleophilic reactivities. In general, the nucleophilicity of the NHOs is much stronger than that of commonly used Lewis bases such as Ph3P or DMAP [4-(dimethylamino)pyridine] but weaker than that of their NHC analogues; however, caution should be taken when generalizing this conclusion to a wide range of electrophiles with distinctively electronic and structural properties.
The amination of aryl halides in liquid ammonia (LNH(3)) is catalyzed by a copper(I) salt/ascorbate system to yield primary aromatic amines in good to excellent yields. The low concentrations of catalyst required and the ease of product isolation suggest that this process has potential industrial applications. Commonly used ligands for analogous metal-catalyzed reactions are not effective. The rate of amination of iodobenzene in liquid ammonia is first order in copper(I) catalyst concentration. The small Hammett ρ = 0.49 for the amination of 4-substituted iodobenzenes in liquid ammonia at 25 °C indicates that the C-I bond is not significantly broken in the transition state structure and that there is a small generation of negative charge in the aryl ring, which is compatible with the oxidative addition of the copper ion being rate limiting.
The rate constants for the reactions of a variety of nucleophiles reacting with substituted benzyl chlorides in liquid ammonia (LNH(3)) have been determined. To fully interpret the associated linear free-energy relationships, the ionization constants of phenols ions in liquid ammonia were obtained using UV spectra. These equilibrium constants are the product of those for ion-pair formation and dissociation to the free ions, which can be separated by evaluating the effect of added ammonium ions. There is a linear relationship between the pK(a) of phenols in liquid ammonia and those in water of slope 1.68. Aminium ions exist in their unprotonated free base form in liquid ammonia and their ionization constants could not be determined by NMR. The rates of solvolysis of substituted benzyl chlorides in liquid ammonia at 25 °C show a Hammett ρ of zero, having little or no dependence upon ring substituents, which is in stark contrast with the hydrolysis rates of substituted benzyl halides in water, which vary 10(7) fold. The rate of substitution of benzyl chloride by substituted phenoxide ions is first order in the concentration of the nucleophile indicative of a S(N)2 process, and the dependence of the rate constants on the pK(a) of the phenol in liquid ammonia generates a Brønsted β(nuc) = 0.40. Contrary to the solvolysis reaction, the reaction of phenoxide ion with 4-substituted benzyl chlorides gives a Hammett ρ = 1.1, excluding the 4-methoxy derivative, which shows the normal positive deviation. The second order rate constants for the substitution of benzyl chlorides by neutral and anionic amines show a single Brønsted β(nuc) = 0.21 (based on the aqueous pK(a) of amine), but their dependence on the substituent in substituted benzyl chlorides varies with a Hammett ρ of 0 for neutral amines, similar to that seen for solvolysis, whereas that for amine anions is 0.93, similar to that seen for phenoxide ion.
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