Phase-transfer agents as catalysts for a nucleophilic substitution reaction in microemulsions

The reaction between 4-tert-butylbenzyl bromide and potassium iodide was carried out in microemulsions based on different nonionic surfactants, and the reaction rates were compared with those obtained in two-phase systems with added phase-transfer agent, either a quaternary ammonium salt or a crown ether. The reactions were relatively fast in the microemulsions and extremely sluggish in the two-phase systems without additional phase-transfer agent. Addition of a phase-transfer agent did not accelerate the reaction when a hydrocarbon was used as organic solvent, neither in the two-phase system nor in the microemulsion. When a chlorinated hydrocarbon was used as solvent, phase-transfer catalysis became effective and the rate obtained in the two-phase system with an equimolar amount of phase-transfer agent added was higher than that obtained in the microemulsion. When a catalytic amount of phase-transfer agent was used, the rate in the two-phase system was about the same as the rate obtained in the microemulsion without the phase-transfer agent. The combined approach, that is, use of a microemulsion as the reaction medium and addition of a phase-transfer agent, gave the highest reaction rate. The quaternary ammonium salt (tetrabutylammonium hydrogen sulfate) was a more efficient catalyst in the microemulsion system than the crown ether ([18]crown-6).     

Acid-catalyzed nucleophilic aromatic substitution: experimental and theoretical exploration of a multistep mechanism

The mechanism for the acid-mediated substitution of a phenolic hydroxyl group with a sulfur nucleophile has been investigated by a combination of experimental and theoretical methods. We conclude that the mechanism is distinctively different in nonpolar solvents (i.e., toluene) compared with polar solvents. The cationic mechanism, proposed for the reaction in polar solvents, is not feasible and the reaction instead proceeds through a multistep mechanism in which the acid (pTsOH) mediates the proton shuffling. From DFT calculations, we found a rate-determining transition state with protonation of the hydroxyl group to generate free water and a tight ion pair between a cationic protonated naphthalene species and a tosylate anion. Kinetic experiments support this mechanism and show that, at moderate concentrations, the reaction is first order with respect to 2-naphthol, n-propanethiol, and p-toluenesulfonic acid (pTsOH). Experimentally determined activation parameters are similar to the calculated values (Delta H exp not equal =105+/-9, Delta H calcd not equal =118 kJ mol(-1); Delta G exp not equal =112+/-18, Delta G calcd not equal =142 kJ mol(-1)).     

Unusual nucleophilic substitution in the nitrophthalimide series

The reactions of 3- and 4-nitrophthalimides with hydroxylamine in aqueous alcohol media were studied. A mixture of 3-amino-4-nitro- and 4-amino-5-nitrophthalimides is formed in the case of 4-nitrosubstituted derivative, whereas 3,6-dihydroxyphthalimide is unexpectedly found to be the main product of the reaction of 4-nitrosubstituted derivative. A possible mechanism of the transformation was suggested. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1250–1252, June, 1998.     

Vicarious nucleophilic substitution of hydrogen versus vinylic substitution of halogen in the reactions of carbanions of halomethyl aryl sulfones with dialkyl halofumarates and halomaleates

Reaction of halomethyl aryl sulfone carbanions with dialkyl halofumarates and halomaleates results in nucleophilic substitution of hydrogen and/or of the halogen. The reaction with halofumarates proceeds via addition of the carbanions to the vinylic carbon atom connected with hydrogen, followed by base promoted β-elimination of hydrogen halide in which the halogen originates from the carbanion moiety or from the alkene. In the case of halomaleates the reaction proceeds via an elimination-addition sequence.     

Retention of configuration in the nucleophilic substitution reactions of some nine-membered ansa derivatives of cyclotriphosphazatriene

X-ray crystallographic evidence shows that nucleophilic substitution reactions of two different types of cyclophosphazene derivatives with relatively rigid nine-membered ansa rings leads to the first demonstration of retention of configuration in these molecular systems.     

Energy landscapes of nucleophilic substitution reactions: a comparison of density functional theory and coupled cluster methods

We have carried out a detailed evaluation of the performance of all classes of density functional theory (DFT) for describing the potential energy surface (PES) of a wide range of nucleophilic substitution (SN2) reactions involving, amongst others, nucleophilic attack at carbon, nitrogen, silicon, and sulfur. In particular, we investigate the ability of the local density approximation (LDA), generalized gradient approximation (GGA), meta-GGA as well as hybrid DFT to reproduce high-level coupled cluster (CCSD(T)) benchmarks that are close to the basis set limit. The most accurate GGA, meta-GGA, and hybrid functionals yield mean absolute deviations of about 2 kcal/mol relative to the coupled cluster data, for reactant complexation, central barriers, overall barriers as well as reaction energies. For the three nonlocal DFT classes, the best functionals are found to be OPBE (GGA), OLAP3 (meta-GGA), and mPBE0KCIS (hybrid DFT). The popular B3LYP functional is not bad but performs significantly worse than the best GGA functionals. Furthermore, we have compared the geometries from several density functionals with the reference CCSD(T) data. The same GGA functionals that perform best for the energies (OPBE, OLYP), also perform best for the geometries with average absolute deviations in bond lengths of 0.06 A and 0.6 degrees, even better than the best meta-GGA and hybrid functionals. In view of the reduced computational effort of GGAs with respect to meta-GGAs and hybrid functionals, let alone coupled cluster, we recommend the use of accurate GGAs such as OPBE or OLYP for the study of SN2 reactions.     

Evidences for the key role of hydrogen bonds in nucleophilic aromatic substitution reactions

The effect of hydrogen bonds on the fate of nucleophilic aromatic substitutions (S(N)Ar) has been studied in silico using a density functional theory approach in the condensed phase. The importance of these hydrogen bonds can explain the "built-in solvation" model of Bunnett concerning intermolecular processes between halogenonitrobenzenes and amines. It is also demonstrated that it can explain experimental results for a multicomponent reaction (the Ugi-Smiles coupling), involving an intramolecular S(N)Ar (the Smiles rearrangement) as the key step of the process. Modeling reveals that when an intramolecular hydrogen bond is present, it lowers the activation barrier of this step and enables the multicomponent reaction to proceed.     

Poly(arylene sulfide)s via nucleophilic aromatic substitution reactions of halogenated pyromellitic diimides

Nucleophilic aromatic substitution (SNAr) reactions are exploited to prepare poly(arylene sulfide)s (PAS's) via the reaction of bis-thiolates and dibrominated pyromellitic diimide (PMDI) derivatives. Small-molecule model studies reveal the reaction is well-defined and proceeds in quantitative yield in practical times at room temperature. Variation in comonomer feed ratios allowed some control over target polymer molecular weights in the step polymerization, but control was likely limited by the relatively poor polymer solubility in the dipolar aprotic solvents typically employed to promote SNAr reactions. One substitution pattern produces a steric “pocket” around the PMDI units, inducing a peculiar solubility trend in halogenated solvents; that is, greatly reduced solubility in CHCl₃ relative to CH₂Cl₂ and C₂H₂Cl₄. One example small-molecule readily dissolves in CHCl₃ at room temperature, then rapidly grows poorly soluble crystals revealed by single-crystal XRD to contain CHCl₃ molecules in the steric pockets. Finally, the recently demonstrated depolymerization of phthalonitrile-based PAS's via ipso substitution with monothiolates as chain scission agents yields quantitative molecular weight reduction to monomeric species from the polymers reported here.     

Structural modification of unsymmetrically substituted monophthalocyanines by nucleophilic reactions

New 2-nitro-substituted phthalocyanine zinc complexes were synthesized. The nucleophilic substitution of the NO₂ group was used for the first time for the structural modification of unsymmetrically substituted monophthalocyanines. The electronic absorption spectra of phthalocyanines were studied. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2036–2040, September, 2005.     

Multistep nucleophilic substitution of the halogen atom in 2-halo-2-alkenals

pso-Substitution of the halogen atom in 2-halo-2-alkenals under the action of secondary amines proceedsvia three consecutive steps: addition, nucleophilic substitution, and -elimination (the Ad_N-S_N-E mechanism). The main intermediates arising in the reactions of 2-chloropropenal and 2-chloro-2-butenal with piperidine were detected by NMR spectroscopy. A general scheme of the reaction is proposed.Translated fromIzvestiya Akademii. Seriya Khimiicheskaya, No 1.pp. 139–142.January, 1996.     

Oxidative nucleophilic substitution: transformation of alkylboronic derivatives

An efficient amidation reaction is described in this paper. Potassium alkyltrifluoroborate salts can be transforming to amides from nitriles in the presence of copper acetate and boron trifluoride. An extension of this reaction allowed the formation of amines, ethers, and C-C bond.     

Lewis base-catalyzed double nucleophilic substitution reaction of N-tosylaziridinofullerene with thioureas or guanidines

Lewis base-catalyzed double nucleophilic substitution reaction of N-tosylaziridinofullerene with thioureas or guanidines affords the fullerothiazolidin-2-imine or fulleroimidazolidin-2-imine derivatives, respectively. In the case of unsymmetrical thioureas connecting an alkyl and an aryl group on each of the nitrogen atom, the transformation exhibits excellent chemoselectivity with only the aryl substituted nitrogen atom bonding to C₆₀. The generated tri-4-methoxyphenyl substituted fulleroimidazolidin-2-imine reacts with CS₂ smoothly to generate di-4-methoxyphenyl fulleroimidazolidin-2-thione.     

Hydroxylation of nitro-(pentafluorosulfanyl)benzenes via vicarious nucleophilic substitution of hydrogen

Para- and meta-nitro-(pentafluorosulfanyl)benzenes react with anions of cumyl hydroperoxide in the presence of t-BuOK in liquid ammonia to form nitro-(pentafluorosulfanyl)phenols. Their reduction with hydrogen in the presence of Raney-Nickel provides amino-(pentafluorosulfanyl)phenols.