Pengju Ji

The Essential Role of Bond Energetics in C–H Activation/Functionalization

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.

Copper(I)-Catalyzed Amination of Aryl Halides in Liquid Ammonia

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 Kinetics and Mechanisms of Aromatic Nucleophilic Substitution Reactions in Liquid Ammonia

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.

Standard and absolute pKa scales of substituted benzoic acids in room temperature ionic liquids.

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.

Liquid Ammonia as a Dipolar Aprotic Solvent for Aliphatic Nucleophilic Substitution Reactions

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.

The kinetics and mechanisms of organic reactions in liquid ammonia

Liquid ammonia is a potentially useful solvent for a variety of organic reactions and so understanding the kinetics and mechanisms of these processes is important. In contrast to the hydrolysis rates of the substituted benzyl halides in water which vary 107-fold, the rates of the solvolysis of substituted benzyl chlorides in liquid ammonia at 25 °C have little or no dependence upon ring substituents and vary only 2-fold between 4-methoxy- and 4-nitro- derivatives. The Hammett ρ-value is practically zero, which suggests there is no significant charge developed on the central carbon in the transition state. Activation energies for solvolysis of 4-nitro-, 4-methoxy-, 4-chloro- and unsubstituted benzyl chloride in liquid ammonia vary from 40.3 to 43.8 kJ mol−1 in the order of NO2 99%) selectivity towards O-benzylation of phenoxide ion, and with 1,2,4-triazolate anion gives predominantly (92%) substitution in the 1-position.

Ionization of Carbon Acids in Liquid Ammonia

The acidities of various carbon acids in liquid ammonia (LNH(3)) at room temperature were determined by NMR and rates of D-exchange. There is a reasonable linear correlation of the pK(a)s in LNH(3) with those in water and DMSO of slope 0.7 and 0.8, respectively. Carbon acids with an aqueous pK(a) of less than 12 are fully ionized in liquid ammonia. Nucleophilic substitution of benzyl chloride by carbanions in liquid ammonia generates a Brønsted β(nuc) = 0.38.

Is Amine a Stronger Base in Ionic Liquid Than in Common Molecular Solvent? An Accurate Basicity Scale of Amines

The equilibrium basicities of 21 frequently used amines in two room-temperature ionic liquids (RTILs) were measured precisely. The standard deviation was much superior to that sparsely reported elsewhere. The data comparisons revealed that amines are stronger bases in ionic ligquids than in DMSO and water but weaker base than in acetonitrile (AN). Interestingly, regression analyses demonstrate that the basicity scales obtained in two RTILs correlate well with that in AN but not with those in water and DMSO.

Copper catalysed azide–alkyne cycloaddition (CuAAC) in liquid ammonia

Copper(I) catalysed azide-alkyne cycloaddition reactions (CuAAC) occur smoothly in liquid ammonia (LNH(3)) at room temperature to give exclusively 1,4-substituted 1,2,3-triazoles with excellent yields (up to 99%). The CuAAC reactions in liquid ammonia require relatively small amounts of copper(I) catalyst (0.5 mole%) compared with that in conventional solvents. The product can be obtained conveniently by simply evaporation of ammonia, indicating its potential application in industry. The rate of the CuAAC reaction in liquid ammonia shows a second order dependence on the copper(I) concentration and the reaction occurs only with terminal alkynes. Deuterium exchange experiments with phenyl acetylene-d(1) show that the acidity of the alkyne is increased at least 1000-fold with catalytic amounts of copper(I) in liquid ammonia. The mechanism of the CuAAC reaction in liquid ammonia is discussed.

A Systematic Theoretical Study on the Acidities for Cations of Ionic Liquids in Dimethyl Sulfoxide

The acidities of 40 commonly seen cations of ionic liquids (CILs) in dimethyl sulfoxide (DMSO) were investigated by a well-established theoretical method, SMD/M06-2X/6-311++G (2df,2p)//B3LYP/6-31+G(d). The calculated p Kas agree excellently with the available experimental data and range from 20.0 to 45.8 with an acidity order of 1,3-dialkylimidazolium > amidinium > pyridinium > tetraalkylphosphonium > morpholinium > pyrrolidinium ≈ piperidinium > guanadinim cations. The established acidity scale in this work provides a useful tool, as verified by the acidity comparisons, to assess the stability of ILs under various extent basic conditions, and also reveals the relative basicity of several classical N-heterocyclic carbenes and olefins as well as ylides.