Catalysis of nucleophilic substitution reactions in supramolecular systems

The factors determining the catalytic effect of supramolecular systems on the nucleophilic substitution reactions are analyzed. The role of the structural and phase transitions of nanoaggregates in the catalytic mechanism are determined. The substrate specificity is shown for different structures of the supramolecular composition.     

Phase-transfer catalysis in reactions of electrophilic aromatic substitution

Electrophilic substitution in aromatic compounds under conditions of phase-transfer catalysis is considered. Catalysts of phase transfer of electrophilic reagents are used; their efficiency and the mechanism of their action in organic solvent-water systems are discussed.This review is based on materials of the report delivered at the Conference Phase-Transfer Catalysis. New Ideas and Methods (March 1994).Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1895–1900, October, 1995.     

New highly stable metallabenzenes via nucleophilic aromatic substitution reaction

Treatment of the ruthenabenzene [Ru{CHC(PPh(3))CHC(PPh(3))CH}Cl(2)(PPh(3))(2)]Cl (1) with excess 8-hydroxyquinoline in the presence of CH(3)COONa under air atmosphere produced the S(N)Ar product [(C(9) H(6)NO)Ru{CHC(PPh(3))CHC(PPh(3))C}(C(9)H(6)NO)(PPh(3))]Cl(2) (3). Ruthenabenzene 3 could be stable in the solution of weak alkali or weak acid. However, reaction of 3 with NaOH afforded a 7:1 mixture of ruthenabenzenes [(C(9)H(6)NO)Ru{CHC(PPh(3))CHCHC}(C(9)H(6)NO)(PPh(3))]Cl (4) and [(C(9)H(6)NO)Ru{CHCHCHC(PPh(3))C}(C(9)H(6)NO)(PPh(3))]Cl (5), presumably involving a P-C bond cleavage of the metallacycle. Complex 3 was also reactive to HCl, which results in a transformation of 3 to ruthenabenzene [Ru{CHC(PPh(3))CHC(PPh(3))C}Cl(2)(C(9)H(6)NO)(PPh(3))]Cl (6) in high yield. Thermal stability tests showed that ruthenabenzenes 4, 5, and 6 have remarkable thermal stability both in solid state and in solution under air atmosphere. Ruthenabenzenes 4 and 5 were found to be fluorescent in common solvents and have spectral behaviors comparable to those organic multicyclic compounds containing large π-extended systems.     

Substituent effects on the stereochemistry of gas-phase intracomplex nucleophilic substitutions

The mechanism and stereochemistry of the intracomplex solvolysis of proton-bound complexes [Y...H...M]+ between M = CH3 (18)OH and Y = 1-arylethanol [(S)-1-(para-tolyl)ethanol (1S), (S)-1-(para-chlorophenyl)ethanol (2S), (S)-1-(meta-alpha,alpha,alpha-trifluoromethylphenyl)ethanol (3S), (S)-1-(para-alpha,alpha,alpha-trifluoromethylphenyl)ethanol (4S), (R)-1-(pentafluorophenyl)ethanol (5R), (R)-alpha-(trifluoromethyl)benzyl alcohol (6R), and (R)-1-phenylethanol (7R)] have been investigated in the gas phase (CH3F; 720 Torr) in the 25-140 degrees C temperature range. Gas-phase solvolysis of [Y...H...M]+ (Y=2S, 3S, 4S, and 7R) leads to extensive racemization above a characteristic temperature t(#) (e.g. at t(#)>60 degrees C for 7R), whereas below that temperature the reaction displays a preferential retention of configuration. Predominant retention of configuration is instead observed in the intracomplex solvolysis of [Y...H...M]+ (Y=1S, 4S, 5R, and 6R) with the temperature range investigated (25 相似文献   

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)).     

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.     

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.     

Regioselective nucleophilic substitution reaction of meso-hexakis(pentafluorophenyl) substituted [26]hexaphyrin

Reaction of various alkoxides led to the selective replacement of the p-fluorine substituents of meso-hexakis(pentafluorophenyl) substituted [26]hexaphyrin. Reaction with isopropyl amine gave meso-hexakis(4-isopropylamino-2,3,5,6-tetrafluorophenyl) substituted [28]hexaphyrin.     

Dramatic enhancement of enone epoxidation rates in nonionic microemulsions

The ability of microemulsions to dissolve polar and non-polar components with a huge internal interface can overcome the reagent incompatibilities frequently encountered in organic reactions. We investigated model epoxidation reactions of alpha,beta-unsaturated enones and alkaline hydrogen peroxide in different nonionic microemulsions, both in the presence and absence of a phase-transfer agent (PTA). The obtained reaction profiles were compared with those for the corresponding surfactant-free two-phase systems. In addition, we defined a time constant tau as a measure for the rate of turnover. The epoxidation of trans-chalcone using an n-alkyl-polyoxyethylene surfactant based microemulsion was fastest in the system with the PTA (tau=66 min) and slightly slower without the PTA (tau=77 min). It was still slower in the two-phase system with a PTA (tau=114 min) and extremely sluggish without a phase-transfer agent. With n-alkyl beta-D-glucopyranoside as the surfactant the conversion was twice as fast than in the former microemulsion systems, but the PTA did not accelerate the reaction further (tau=35 and 33 min). The epoxidation of vitamin K(3), the second model system, was extremely accelerated. It proceeded a factor of approximately 35 faster in the microemulsion (tau=1.44 min) than in the corresponding two-phase system (tau=57 min).     

PEG 400 promoted nucleophilic substitution reaction of halides into organic azides under mild conditions

Abstract

Polyethylene glycol 400 (PEG 400) has been demonstrated as an efficient and eco-friendly reaction medium for the preparation of organic azides from structurally diverse halides by nucleophilic substitution reaction with NaN₃ under mild conditions. The advantages of this protocol are: operational simplicity, environmental safety, broad substrate scope, excellent functional group tolerance, and short reaction time. The PEG 400 can be recovered and reused.     

Alkali-metal-ion catalysis and inhibition in the nucleophilic displacement reaction of y-substituted phenyl diphenylphosphinates and diphenylphosphinothioates with alkali-metal ethoxides: effect of changing the electrophilic center from P=O to P=S

A kinetic study of the nucleophilic substitution reaction of Y‐substituted phenyl diphenylphosphinothioates 2 a – g with alkali‐metal ethoxides (MOEt; M=Li, Na, K) in anhydrous ethanol at (25.0±0.1) °C is reported. Plots of pseudo‐first‐order rate constants (k_obsd) versus [MOEt], the alkali ethoxide concentration, show distinct upward (KOEt) and downward (LiOEt) curvatures, respectively, pointing to the importance of ion‐pairing phenomena and a differential reactivity of dissociated EtO^? and ion‐paired MOEt. Based on ion‐pairing treatment of the kinetic data, the k_obsd values were dissected into k and k_MOEt, the second‐order rate constants for the reaction with the dissociated EtO^? and ion‐paired MOEt, respectively. The reactivity of MOEt toward 2 b (Y=4‐NO₂) increases in the order LiOEt?NaOEt>KOEt>EtO^?. The current study based on Yukawa–Tsuno analysis has revealed that the reactions of 2 a – g (P?S) and Y‐substituted phenyl diphenylphosphinates 1 a – g (P?O) with MOEt proceed through the same concerted mechanism, which indicates that the contrasting selectivity patterns are not due to a difference in reaction mechanism. The P?O compounds 1 a – g are approximately 80‐fold more reactive than the P?S compounds 2 a – g toward the dissociated EtO^? (regardless of the electronic nature of substituent Y) but are up to 3.1×10³‐fold more reactive toward ion‐paired LiOEt. The origin of the contrasting selectivity patterns is further discussed on the basis of competing electrostatic effects and solvational requirements as a function of anionic electric field strength and cation size (Eisenman’s theory).     

Use of acetate as a leaving group in palladium-catalyzed nucleophilic substitution of benzylic esters

The palladium complex prepared in situ from [Pd(η³-C₃H₅)(cod)]BF₄ and bidentate phosphine DPPF was a good catalyst for the nucleophilic substitution of benzyl acetate. Significant acceleration of the palladium-catalyzed substitution was observed when an alcohol was employed as a reaction solvent. The palladium catalyst was effective for the benzylation of various stabilized carbanions, amines, and benzenesulfinate with benzylic acetates.     

A nucleophilic substitution reaction in microemulsions based on either an alcohol ethoxylate or a sugar surfactant

A nucleophilic substitution reaction between 4-tert-butylbenzyl bromide and a series of iodide salts has been performed in oil-in-water microemulsions based on either a fatty alcohol ethoxylate or a sugar surfactant. The reaction kinetics was compared with the kinetics of the same reaction performed in a microhomogeneous reaction medium, d-MeOH. Previous results showing a particularly high reactivity in the microemulsion based on the fatty alcohol ethoxylate was confirmed. It was shown that in both microemulsions the reaction rate was almost independent of the choice of counterion to iodide. This indicates that complexation of the cation with the surfactant headgroup, which, in particular, could have taken place with surfactants containing oligooxyethylene chains (a “crown ether effect”), seems not to be of importance.

¹²⁷I NMR studies, as well as quadrupole splitting experiments performed by ²H NMR, indicate that there is a certain accumulation of iodide at the oil–water interface of the microemulsions. It is difficult to draw any quantitative conclusions in this respect, however.

The results obtained in this study, combined with results from previous investigations of the same reaction, indicate that the unexpectedly high reactivity obtained in the microemulsion based on a surfactant containing an oligooxyethylene headgroup is most probably due to the nucleophile being poorly solvated when present in the headgroup layer of such a microemulsion. Poorly solvated anions are known to be highly reactive nucleophiles.     

Phthalide as an activating group for the synthesis of poly(aryl ether phthalide)s by nucleophilic aromatic substitution

The phthalide ring was examined as an activating group for nucleophilic aromatic substitution. The proposed mechanism by which activation occurs is through a ring opening of the phthalide ring to form a Meisenheimer‐like σ complex. 3,3‐Bis(4‐fluorophenyl)phthalide was synthesized and examined under different reaction conditions to determine its suitability for polymer formation. Semiempirical calculations at the PM3 level suggested that 3,3‐bis(4‐fluorophenyl)phthalide is only moderately activated, whereas ¹H, ¹³C, and ¹⁹F NMR spectroscopy suggested that the monomer was not sufficiently activated for nucleophilic aromatic substitution. However, low‐molecular‐weight polymers (number‐average molecular weight < 7000 g/mol) were produced from bisphenol A, hydroquinone, and phenolphthalein. The polymers were characterized by gel permeation chromatography, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry, NMR spectroscopy, and differential scanning calorimetry. The polymers displayed relatively high glass‐transition temperatures. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3046–3054, 2002     

人类谷胱甘肽S-转移酶M1a-1a催化的亲核芳香取代反应的理论研究

利用分子力学和量子力学方法研究人类谷胱甘肽S-转移酶M1a-1a催化谷胱甘肽对1-氯-2,4二硝基苯(CDNB)的亲核芳香取代反应的细节.所获得的反应路径显示反应仅经历一个过渡态且能垒很低.电荷布居分析证明电子从谷胱甘肽基团流向二硝基苯,验证了反应的发生.计算结果表明活性位点3个残基(Tyr6,His107和Tyr115)参与了催化反应,尤其是His107,它在反应后期通过与产物形成氢键从而加速了Cl的释放.结果支持了Patskovsky等人提出的机理,并有助于其他谷胱甘肽S-转移酶的研究.