Phenolysis and aminolysis of 4‐nitrophenyl and 2,4‐dinitrophenyl S‐methyl thiocarbonates in aqueous ethanol

The reactions of S‐methyl O‐(4‐nitrophenyl) thiocarbonate ( 1 ) and S‐methyl O‐(2,4‐dinitrophenyl) thiocarbonate ( 2 ) with a series of secondary alicyclic (SA) amines and phenols are subjected to a kinetic investigation. Under nucleophile excess, pseudo‐first‐order rate coefficients (k_obs) are obtained. Plots of k_obs against the free nucleophile concentration at constant pH are linear with slopes k_N. The Brønsted plots (log k_N vs. nucleophile pK_a) for the reactions are linear with slope (β) values in the 0.5–0.7 range, in accordance with concerted mechanisms. Comparison of the SA aminolysis of 1 with the same one carried out in water shows that the change of solvent from water to aqueous ethanol destabilizes the zwitterionic tetrahedral intermediate, changing the mechanism from stepwise to concerted. This destabilization is greater than that due to the change from SA amines to quinuclidines. For the phenolysis reactions, the k_N values in aqueous ethanol are smaller than those for the same reactions in water. Considering that the nucleophile is an anion, this result is unexpected because the anion should be more stabilized in the more polar solvent. This result is explained by the facts that the phenoxide reactant has a negative charge that is delocalized in the aromatic ring and the transition state is highly polar. © 2011 Wiley Peiodicals, Inc. Int J Chem Kinet 43: 353–358, 2011     

Dual Nucleophilic Substitution Reactions of O,O‐Diethyl 2,4‐dinitrophenyl Phosphate and Thionophosphate Triesters

The reactions of the title compounds with phenoxides, secondary alicyclic (SA) amines, and pyridines, in 44 wt% ethanol–water, at 25°C and an ionic strength of 0.2 M, were subjected to kinetic and product studies. From analytical techniques (HPLC and NMR), two pathways were detected (nucleophilic attack at the phosphoryl center and at the C‐1 aromatic carbon) for the reactions of all the nucleophiles with the phosphate ( 2 ) and for the pyridinolysis of the thionophosphate ( 1 ). Only aromatic nucleophilic substitution was found for the reactions of 1 with phenoxides and SA amines. For the dual reactions, the nucleophilic rate constants (k_N) were separated in two terms: $k_{\rm N}^{\rm P}$ and $k_{\rm N}^{{\rm Ar}}$, which are the rate constants for the corresponding electrophilic centers. The absence of a break in the Brønsted‐type plots for the attack at P is consistent with concerted mechanisms. The Brønsted slopes, β_Ar 0.32–0.71, for the attack at the aromatic C‐1, are in agreement with stepwise mechanisms where formation of a Meisenheimer complex is the rate‐determining step. © 2013 Wiley Periodicals, Inc. Int J Chem Kinet 45: 202–211, 2013     

Concerted aminolysis of diaryl carbonates: Kinetic sensitivity on the basicity of the nucleophile,nonleaving group,and nucleofuge

The kinetics of the reactions of 4‐methylphenyl, phenyl, and 4‐chlorophenyl 2,4,6‐trinitrophenyl carbonates ( 1 , 2 , and 3 , respectively) with a series of anilines and secondary alicyclic (SA) amines has been carried out spectrophotometrically in 44 wt% ethanol–water, at 25.0°C, ionic strength 0.2 M. The Brønsted plots (statistically corrected) for the reactions of carbonates 1 – 3 with anilines and SA amines were linear with slopes (β_N) in the range of 0.69–0.78 and 0.45–0.48, respectively, attributed to a concerted mechanism. The negative values found for the sensitivity of log k_N to the basicity of the nonleaving (β_nlg) and leaving (β_lg) groups are discussed. Anilines are more reactive than isobasic SA amines, probably because of the greater steric hindrance offered by the latter. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 604–611, 2012     

Anilinolysis of reactive aryl 2,4‐dinitrophenyl carbonates: Kinetics and mechanism

The reactions of a series of anilines with phenyl 2,4‐dinitrophenyl ( 1 ), 4‐nitrophenyl 2,4‐dinitrophenyl ( 2 ), and bis(2,4‐dinitrophenyl) ( 3 ) carbonates are subjected to a kinetic investigation in 44 wt% ethanol–water, at 25.0 ± 0.1°C and an ionic strength of 0.2 M. Under amine excess pseudo‐first‐order rate coefficients (k_obs) are obtained. Plots of k_obs against free amine concentration at constant pH are linear, with slopes k_N. The Brønsted plots (log k_N vs. anilinium pK_a) for the anilinolysis of 1 – 3 are linear, with slope (β) values of 0.52, 0.61, and 0.63, respectively. The values of these slopes and other considerations suggest that these reactions are ruled by a concerted mechanism. For these reactions, the k_N values follow the reactivity sequence: 3 > 2 > 1 . Namely, the reactivity increases as the number of nitro groups attached to the nonleaving group increases. Comparison of the reactions of this work with the stepwise pyridinolysis of carbonates 1 – 3 indicates that the zwitterionic tetrahedral intermediate (T^±) formed in the pyridinolysis reactions is destabilized by the change of its pyridino moiety by an isobasic anilino group. This is attributed to the superior leaving ability from the T^± intermediate of anilines, relative to isobasic pyridines, which destabilize kinetically this intermediate. The k_N values for the anilinolysis of carbonates 1 – 3 are similar to those found in the reactions of these carbonates with secondary alicyclic amines. With the kinetic data for the anilinolysis of the title substrates and 4‐methylphenyl and 4‐chlorophenyl 2,4‐dinitrophenyl carbonates, a multiparametric equation is derived for log k_N as a function of the pK_a of the conjugate acids of anilines and nonleaving groups. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 191–197, 2011     

Brønsted Acid Mediated Novel Rearrangements of Diarylvinylidenecyclopropanes and Mechanistic Investigations Based on DFT Calculations

Diarylvinylidenecyclopropanes undergo a novel rearrangement in the presence of the Brønsted acid Tf₂NH (Tf: trifluoromethanesulfonyl) to give the corresponding naphthalene derivatives in good to high yields upon heating, whereas in the presence of the Brønsted acid toluene‐4‐sulfonic acid (p‐TSA), the corresponding triene derivatives are afforded in moderate to good yields under mild conditions. Corresponding mechanistic studies on the basis of density functional theory (DFT) with the Gaussian03 program by using the B3LYP method have revealed that the pK_a value of the Brønsted acid, as well as the entropy and solvent effects, plays a significant role in this reaction; these factors can discriminate the differences in the reactivity and regioselectivity among the Brønsted acids used in this reaction. In the presence of Lewis acid Sn(OTf)₂, a butatrienecyclopane can produce the corresponding ring‐opened products in moderate yields.     

A Spiro Phosphamide Catalyzed Enantioselective Proton Transfer of Ylides in a Free Carbene Insertion into N−H Bonds

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pK_a Brønsted acid catalysts that enable free carbene insertion into N−H bonds of amines to prepare chiral α-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pK_a Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton-transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.     

Enantioselective Addition Reaction of Azlactones with Styrene Derivatives Catalyzed by Strong Chiral Brønsted Acids

An enantioselective intermolecular addition reaction of azlactones, as carbon nucleophiles, with styrene derivatives, as simple olefins, was demonstrated using a newly developed chiral Brønsted acid catalyst, namely, F₁₀BINOL‐derived N‐triflyl phosphoramide. Addition products having vicinal tetrasubstituted carbon centers, one of which is an all‐carbon quaternary stereogenic center, were formed in good yields with moderate to high stereoselectivities. Extremely high acidity of the new chiral Brønsted acid was confirmed by its calculated pK_a value based on DFT studies and is the key to accomplishing not only high catalytic activity but also efficient stereocontrol in the intermolecular addition.     

Aminolysis of 2,4-dinitrophenyl X-substituted benzoates and Y-substituted phenyl benzoates in MeCN: effect of the reaction medium on rate and mechanism

Second‐order rate constants (k_N) have been determined spectrophotometrically for the reactions of 2,4‐dinitrophenyl X‐substituted benzoates ( 1 a – f ) and Y‐substituted phenyl benzoates ( 2 a – h ) with a series of alicyclic secondary amines in MeCN at 25.0±0.1 °C. The k_N values are only slightly larger in MeCN than in H₂O, although the amines studied are approximately 8 pK_a units more basic in the aprotic solvent than in H₂O. The Yukawa–Tsuno plot for the aminolysis of 1 a – f is linear, indicating that the electronic nature of the substituent X in the nonleaving group does not affect the rate‐determining step (RDS) or reaction mechanism. The Hammett correlation with σ^? constants also exhibits good linearity with a large slope (ρ_Y=3.54) for the reactions of 2 a – h with piperidine, implying that the leaving‐group departure occurs at the rate‐determining step. Aminolysis of 2,4‐dinitrophenyl benzoate ( 1 c ) results in a linear Brønsted‐type plot with a β_nuc value of 0.40, suggesting that bond formation between the attacking amine and the carbonyl carbon atom of 1 c is little advanced in the transition state (TS). A concerted mechanism is proposed for the aminolysis of 1 a – f in MeCN. The medium change from H₂O to MeCN appears to force the reaction to proceed concertedly by decreasing the stability of the zwitterionic tetrahedral intermediate (T^±) in aprotic solvent.     

Nucleophilicities and carbon basicities of pyridines

Rate and equilibrium constants for the reactions of pyridines with donor‐substituted benzhydrylium ions have been determined spectrophotometrically. The correlation equation log k(20 °C)=s(N+E), in which s and N are nucleophile‐specific parameters and E is an electrophile‐specific parameter, has been used to determine the nucleophilicity parameters of various pyridines in CH₂Cl₂ and aqueous solution and to compare them with N of other nucleophiles. It is found that the nucleophilic organocatalyst 4‐(dimethylamino)pyridine (DMAP) and tertiary phosphanes have comparable nucleophilicities and carbon basicities despite widely differing Brønsted basicities. For that reason, these reactivity parameters are suggested as guidelines for the development of novel organocatalysts. The Marcus equation is employed for the determination of the intrinsic barriers of these reactions.     

Analysis of linear free-energy relationships combined with activation parameters assigns a concerted mechanism to alkaline hydrolysis of x-substituted phenyl diphenylphosphinates

A kinetic study is reported for alkaline hydrolysis of X‐substituted phenyl diphenylphosphinates ( 1 a – i ). The Brønsted‐type plot for the reactions of 1 a – i is linear over 4.5 pK_a units with β_lg=?0.49, a typical β_lg value for reactions which proceed through a concerted mechanism. The Hammett plots correlated with σ^o and σ^? constants are linear but exhibit many scattered points, while the corresponding Yukawa–Tsuno plot results in excellent linear correlation with ρ=1.42 and r=0.35. The r value of 0.35 implies that leaving‐group departure is partially advanced at the rate‐determining step (RDS). A stepwise mechanism, in which departure of the leaving group from an addition intermediate occurs in the RDS, is excluded since the incoming HO^? ion is much more basic and a poorer nucleofuge than the leaving aryloxide. A dissociative (D_N + A_N) mechanism is also ruled out on the basis of the small β_lg value. As the substituent X in the leaving group changes from H to 4‐NO₂ and 3,4‐(NO₂)₂, ΔH ^≠ decreases from 11.3 kcal mol^?1 to 9.7 and 8.7 kcal mol^?1, respectively, while ΔS ^≠ varies from ?22.6 cal mol^?1 K^?1 to ?21.4 and ?20.2 cal mol^?1 K^?1, respectively. Analysis of LFERs combined with the activation parameters assigns a concerted mechanism to the current alkaline hydrolysis of 1 a – i .     

Nonlinear Brønsted and Hammett Correlations Associated with Reactions of 4‐Chloro‐7‐nitrobenzofurazan with Anilines in Dimethyl Sulfoxide Solution

The kinetics and mechanism of nucleophilic aromatic substitution reactions of 4‐chloro‐7‐nitrobenzofurazan 1 with 4‐X‐substituted anilines 2a–g (X = OH, OCH₃, CH₃, H, I, Cl, and CN) are investigated in a dimethyl sulfoxide (Me₂SO) solution at 25°C. The Hammett plot of log k₁ versus σ is nonlinear for all the anilines studied due to positive deviations of the electron‐donating substituents. However, the corresponding Yukawa–Tsuno plot resulted in a good linear correlation with σ+r (σ⁺?σ). The corresponding Brønsted‐type plot is also nonlinear, i.e., the slope (β_nuc) changes from 1.60 to 0.56 as the basicity of anilines decreases. These results indicate a change in a mechanism from a polar S_NAr process for less basic nucleophiles (X = I, Cl, and CN) to a single electron transfer for more basic nucleophiles (X = OH, OCH₃, and CH₃). The satisfactory log k₁ versus E^o correlation obtained for the reactions of 1 with anilines 2a–d in the present system is consistent with the proposed mechanism. Interestingly, the β_nuc = 1.60 value measured for 1 in Me₂SO reflects one of the highest coefficients Brønsted ever observed for S_NAr reactions. © 2013 Wiley Periodicals, Inc. Int J Chem Kinet 45: 152–160, 2013     

Solvent Effects in Acid‐Catalyzed Biomass Conversion Reactions

Reaction kinetics were studied to quantify the effects of polar aprotic organic solvents on the acid‐catalyzed conversion of xylose into furfural. A solvent of particular importance is γ‐valerolactone (GVL), which leads to significant increases in reaction rates compared to water in addition to increased product selectivity. GVL has similar effects on the kinetics for the dehydration of 1,2‐propanediol to propanal and for the hydrolysis of cellobiose to glucose. Based on results obtained for homogeneous Brønsted acid catalysts that span a range of pK_a values, we suggest that an aprotic organic solvent affects the reaction kinetics by changing the stabilization of the acidic proton relative to the protonated transition state. This same behavior is displayed by strong solid Brønsted acid catalysts, such as H‐mordenite and H‐beta.     

A Supramolecular Model for the Co-Catalytic Role of Nitro Compounds in Brønsted Acid Catalyzed Reactions

Nitro compounds are known to change reaction rates and kinetic concentration dependence of Brønsted-acid-catalyzed reactions. Yet, no mechanistic model exists to account for these observations. In this work, an atomistic model for the catalytically active form for an alcohol dehydroazidation reaction is presented, which is generated by DFT calculations and consists of an H-bonded aggregate of two molecules of Brønsted acid and two molecules of nitro compound. The computed O−H stretching frequencies for the aggregate indicate they are stronger acids than the individual acid molecules and serve as predictors for experimental reaction rates. By applying the model to a chemically diverse set of potential promoters, it was predicted and verified experimentally that sulfate esters induce a similar co-catalytic effect. The important implication is that Brønsted-acid catalysis must be viewed from a supramolecular perspective that accounts for not only the pK_a of the acid and the bulk properties of a solvent, but also the weak interactions between all molecules in solution.     

Kinetic Studies on SNAr Reactions of Substituted Benzofurazan Derivatives: Quantification of the Electrophilic Reactivities and Effect of Amine Nature on Reaction Mechanism

Kinetics of the nucleophilic aromatic substitution reactions of 7‐L‐4‐nitrobenzofurazans 1 ( 1a : L = Cl and 1b : L = OCH₃) and secondary cyclic amines (morpholine, piperidine, and pyrolidine) 2a–c have been measured in acetonitrile solution at 20°C. The derived values of second‐order rate constants (k ₁) have been employed to determine the electrophilicity parameters E for both benzofurazans 1a and 1b according to the linear free enthalpy relationship: log k (20°C) = s_N(E + N ) (Eq. 1 ). The second‐order rate constants for reactions of benzofurazans 1 with a series of 4‐X‐substituted anilines 3a–d (X = OH, OCH₃, CH₃, and H) have also been measured in MeCN and found to agree within a factor of 0.14–50 with those calculated by Eq. 1 from the electrophilicity parameters E measured in this work and the known nucleophile‐specific parameters N and s _N of anilines 3 . On the other hand, the reactions of these benzofurazans 1 with anilines 3 exhibit linear Brønsted‐type plots with β_nuc = 1.27 for 1a and 1.01 for 1b , which are considerably greater than those (0.57 for 1a and 0.62 for 1b ) obtained with the secondary cyclic amines 2 . These high values of β_nuc have been interpreted in terms of a single electron transfer mechanism. Secondary evidence for the validity of this mechanism is provided by the agreement between the rate constants, k ₁, for substitution of benzofurazans 1 by the anilines 3 and their oxidation potentials E °.     

Zwitterion/Brønsted Acid Mixtures Showing Controlled Lower Critical Solution Temperature‐Type Phase Changes with Water

A new ammonium‐type zwitterion (ZI), N,N‐dihexyl‐N‐monopentyl‐3‐sulfonyl‐1‐propaneammonium (N₆₆₅C3S) with adequate hydrophobicity showed reversible and highly temperature‐sensitive lower critical solution temperature (LCST)‐type phase transitions after being mixed with pure water. Generally for such compounds, those with longer alkyl chains were immiscible with water and those with shorter chains were miscible with water, regardless of temperature. A slightly more hydrophobic ZI than N₆₆₅C3S showed LCST‐type phase behavior with water when it was mixed with equimolar amounts of a Brønsted acid such as trifluoromethanesulfonic acid (HTfO). The phase‐transition temperature of the ZI/Brønsted acid mixed aqueous solution was controllable by water content.     

Intramolecular catalysis and the rate-determining step in the alkaline hydrolysis of ethyl salicylate

The alkaline hydrolysis of ethyl salicylate has been studied at 35°C within the [ōH] range of 0.001–2.00 M. The observed hydroxide ion concentration dependence of rate has been explained by proposing the occurrence of two parallel kinetic steps shown as in the rate law: rate = k₁[H₂O] [ES ] + k₂[ōH] [ES ] where ES^? represents ionized ethyl salicylate. The value of k₁, is ca. 10⁶ times larger than the expected value of rate constant for uncatalyzed aqueous cleavage of ethyl-p-hydroxybenzoate. This rate advantage is attributed to intramolecular general base catalysis. The analysis of observed activation parameters indicates that ca. 10⁶ times rate enhancement is entirely due to favorable entropy change. The Brønsted-type plots show an extremely low sensitivity of rate constants k₁ and k₂ with respective Brønsted coefficient of β = ?0.03 ± 0.01 and β = ?0.01 ± 0.05, on the basicity of leaving groups of salicylate esters (alkoxide and phenoxide ions). The low values of these Brønsted coefficients indicate essentially little or an insignificant amount of bond cleavage between carbonyl carbon and leaving group in the rate-determining step in both the k₁ and k₂ steps. The rate constants obtained at different ethanol concentration follow Grunwald-Winstein mY equation with m = 0.14 ± 0.01.     

Transesterification Kinetics Investigation of R‐Substituted Phenyl Benzoates with 4‐Methoxyphenol in the Presence of K2CO3 in DMF

Transesterification of R‐substituted phenyl benzoates 1–5 with 4‐methoxyphenol 6 was kinetically investigated in the presence of K₂CO₃ in dimethylformamide (DMF) at various temperatures. The Hammett plots for the reactions of the 1–5 demonstrate good linear correlations with σ⁰ constants. Low magnitude of ρ_LG values indicate that the leaving group departure occurs after the rate‐determining step. The Brønsted coefficient values for the reactions (?0.2, ?0.16, ?0.13 at 15, 24, 36°C, respectively) demonstrate the weak effect of leaving group substituent on the reactivity of R‐substituted phenyl benzoates 1–5 for the reactions with 4‐methoxyphenol 6 in the presence of K₂CO₃ in DMF. The leaving group substituent effect on free energy (ΔG^≠), enthalpy (ΔH^≠), and entropy (ΔS^≠) of activation was examined. It was shown that the activation parameters obtained depend weakly on the leaving group substituent effect. The reaction is entropy controlled in case the leaving group substituent becomes electron withdrawing.     

Phosphonate‐Modified UiO‐66 Brønsted Acid Catalyst and Its Use in Dehydra‐Decyclization of 2‐Methyltetrahydrofuran to Pentadienes

Phosphorus‐modified all‐silica zeolites exhibit activity and selectivity in certain Brønsted acid catalyzed reactions for biomass conversion. In an effort to achieve similar performance with catalysts having well‐defined sites, we report the incorporation of Brønsted acidity to metal–organic frameworks with the UiO‐66 topology, achieved by attaching phosphonic acid to the 1,4‐benzenedicarboxylate ligand and using it to form UiO‐66‐PO₃H₂ by post‐synthesis modification. Characterization reveals that UiO‐66‐PO₃H₂ retains stability similar to UiO‐66, and exhibits weak Brønsted acidity, as demonstrated by titrations, alcohol dehydration, and dehydra‐decyclization of 2‐methyltetrahydrofuran (2‐MTHF). For the later reaction, the reported catalyst exhibits site‐time yields and selectivity approaching that of phosphoric acid on all‐silica zeolites. Using solid‐state NMR and deprotonation energy calculations, the chemical environments of P and the corresponding acidities are determined.     

Activating Pronucleophiles with High pKa Values: Chiral Organo‐Superbases

Direct deprotonation represents an extremely simple, straightforward, and atom‐economic strategy to activate pronucleophiles bearing an acidic proton. However, the difficulty often arises in activating pronucleophiles with high pK_a values by using conventional chiral tertiary amines. To overcome this challenge, a handful of novel chiral Brønsted superbases, including amidines, guanidines, cyclopropenimines, and iminophosphoranes, have been discovered in recent years. This minireview focuses on the application of these organo‐superbases in the catalytic asymmetric reactions of weakly acidic pronucleophiles, and highlights their comparison to the conventional tertiary amines, demonstrating the highly efficient deprotonation processes and stereoselectivity controlled conversions of the superbases. The advantage of these new superbases brings a great opportunity for developing more asymmetric transformations of weakly acidic pronucleophiles.     

An efficient one‐pot synthesis of bis‐indolylmethanes containing pyrazolyl catalyzed by Brønsted acidic ionic liquid under solvent‐free conditions

Brønsted acidic ionic liquid [PyNCH₂CO₂H][HSO₄] was found to be an effective catalyst for the condensation reactions of indoles with various 4‐formylpyrazoles to afford the corresponding bis‐indolylmethanes containing pyrazole under solvent‐free conditions. The satisfactory results were obtained with excellent yields, short reaction time, and simplicity in the experimental procedure. J. Heterocyclic Chem., (2011).