Nucleophilic aromatic substitution of hydrogen through lithiated phosphine borane complexes and N-phosphorylphosphazenes

Organophosphorus compounds containing nitroaryl and cyanoaryl groups have been prepared in good yield through nucleophilic aromatic substitution of hydrogen using α-lithiated phosphazenes and phosphine borane complexes as nucleophiles. In all cases, nearly exclusive replacement of the hydrogen in the para position with respect to the activating group has been observed.     

Nucleophilic aromatic substitution reactions of 1,2-dihydro-1,2-azaborine

Could go either way: The addition of nucleophiles to the parent 1,2-dihydro-1,2-azaborine and subsequent quenching with an electrophile generates novel substituted 1,2-azaborine derivatives. Mechanistic studies are consistent with two distinct nucleophilic aromatic substitution pathways depending on the nature of the nucleophile.     

Nucleophilic aromatic substitution reaction of nitroarenes with alkyl- or arylthio groups in dimethyl sulfoxide by means of cesium carbonate

Treatment of nitroarenes having electron-withdrawing groups at the ortho or para position with alkanethiol in the presence of cesium carbonate in dimethyl sulfoxide at 25 °C leads to nucleophilic displacement of the nitro group with the alkylthio group. Cesium carbonate is superior to other bases such as potassium carbonate, sodium carbonate, and triethylamine. The cesium-mediated nucleophilic aromatic substitution reaction provides a mild yet powerful and user-friendly protocol for the synthesis of aryl sulfides.     

Direct synthesis of trimethyl(2-phenoxyethyl)silanes from aromatic fluorides

A direct synthesis of trimethyl(2-phenoxyethyl)silanes from the corresponding aromatic fluorides and 2-(trimethylsilyl)ethanol was developed. A variety of substituents were tolerated and a substitution reaction using 1-bromo-3-chloro-5-fluorobenzene was demonstrated.     

Transition metal carbene chemistry: Nucleophilic substitution reactions of imidazolide and benzimidazolide ions with Fischer carbene complexes in MeOH

Rate constants for the nucleophilic substitution reactions of imidazolide (IZ⁻) and benzimidazolide (BIZ⁻) ions with 4-Cr-Z and 5 in MeOH at 25 °C are reported and Hammett ρ values are evaluated to be 1.50 ± 0.10 and 1.51 ± 0.08 for 4-Cr-Z-IZ⁻ and 4-Cr-Z-BIZ⁻ reactions, respectively. The comparable reactivity and also almost identical ρ values for these reactions indicate that there is no difference in sensitivity towards electronic effects due to slightly bigger size of BIZ⁻ over IZ⁻ and bond formation at the transition states are equally progressed. The higher ρ values for these reactions compared to those with a wide range of nucleophiles may arise mainly due to lower polarity of the solvent MeOH which enhances the requirement for stabilization of the negative charge in the transition state by the Z-substituents.     

Ultrasound-promoted aromatic nucleophilic substitution of dichlorobenzene iron(II) complexes

The nucleophilic aromatic substitution under ultrasound irradiation of a dichlorobenzene iron η⁶-complex with various secondary amines is reported. The reaction time at moderate temperatures is considerably shortened (15 min) compared to non sonicated reaction conditions at room temperature (several days) or at solvent refluxing temperature (12-48 h). Controlled mono- or di-substitution was achieved by the tuning of the amine nucleophilicity and the solvent polarity. The method was successfully applied to the synthesis of differently substituted phenylenediamines.     

Nucleophilic substitution of (sulfonyloxymethyl)aziridines: an asymmetric synthesis of both isomers of mexiletine

The nucleophilic substitution reactions of 1-[1′(R)-α-methylbenzyl]-(2R)- and (2S)-(sulfonyloxymethyl)aziridines were carried out with various nucleophiles including N₃⁻, MeO⁻, CN⁻, SCN⁻, and diarylcuprates. The reaction pathway is influenced by the stereochemistry of the substrates, nucleophiles, and also the structure of the leaving groups. When the reaction site is less sterically hindered for the reactive nucleophiles to approach to the substrate 1-[1′(R)-α-methylbenzyl]-(2S)-(p-toluenesulfonyloxymethyl)aziridines, product is obtained as a single isomer while all the other starting materials afford a mixture of two isomers from two different reaction pathways. Application of this method enabled us to prepare both isomers of orally effective antiarrhythmic agent mexiletine.     

A practical synthesis of optically active aromatic epoxides via asymmetric transfer hydrogenation of α-chlorinated ketones with chiral rhodium-diamine catalyst

A practical method for the synthesis of optically active aromatic epoxides has been developed via the formation of optically active α-chlorinated alcohols and intramolecular etherification. Optically active alcohols with up to 99% ee can be obtained from the asymmetric reduction of aromatic ketones with a substrate/catalyst ratio of 1000-5000 using a formic acid/triethylamine mixture containing a well-defined chiral Rh complex, Cp*RhCl[(R,R)-Tsdpen]. The asymmetric reduction of α-chlorinated aromatic ketones with a chiral Rh catalyst is characterized by a rapid and carbonyl group-selective transformation because of the coordinatively saturated nature of diamine-based Cp*Rh(III) hydride complexes. The outcome of the reduction is significantly influenced by the structures of the ketonic substrates as well as the hydrogen source such as formic acid or 2-propanol. Commercially available reagents and solvents can be used in this reaction without special purification. This epoxide synthetic process in either a one- or two-pot procedure is practical and particularly useful for the large-scale production of optically active styrene oxides from α-chlorinated ketones.     

Study of Ultrasound Promoted Aromatic Nucleophilic Substitution of Halobenzenes with Amines

Summary.  The sonochemical nucleophilic aromatic substitution of substituted haloarenes with different amines were studied. The reaction course was found to be strongly depended on basicity, bulkiness, and boiling point of amines as well as on the electron-withdrawing property of the substituents. Corresponding author. E-mail: toma@fns.uniba.sk Received May 6, 2002; accepted (revised) May 29, 2002     

The umpolung of substituent effect in nucleophilic aromatic substitution. A new approach to the synthesis of N,N-disubstituted melamines (triazine triskelions) under mild reaction conditions

By the umpolung of substituent effect 1,3,5-triazines substituted with three dialkylamino groups were prepared under mild reaction conditions by treatment of cyanuric chloride with tertiary amines. Quaternary N-triazinylammonium salts were identified as reactive intermediates activating the triazine ring and strongly promoting the persubstitution of all chlorine atoms. The final degradation of intermediate N-triazinylammonium chlorides proceeded at room temperature or in boiling dichloromethane spontaneously within irreversible evolution of appropriate chloroalkane.     

Reactions of 3-R-5-nitropyridines with nucleophiles: Nucleophilic substitution vs conjugate addition

A number of 3-R-5-nitropyridines were synthesized and their reactions with various types of nucleophiles were investigated. The reaction outcome depends on the nature of a nucleophile: in case of anionic O-, N- and S-nucleophiles the previously unreported substitution of non-activated nitro group occurred while carbon nucleophiles underwent dearomatization of the pyridine ring with the formation of products of 1,2- and 1,4-addition.     

Facile synthesis,X-ray analysis,and spectroscopic studies of di-iron propanedithiolate complexes with tris(aromatic)phosphine ligands

Three new propanedithiolate-type iron–sulfur complexes containing tris(aromatic)phosphine ligands, [{(μ-SCH₂)₂CH₂}Fe₂(CO)₅L] (L?=?P(PhOMe-p)₃, 1; P(PhMe-p)₃, 2; P(PhF-p)₃, 3), have been prepared through carbonyl substitution in the presence of Me₃NO. The new complexes 1–3 were characterized by elemental analysis, IR, ¹H, ¹³C{¹H}, and ³¹P{H} NMR spectra. The molecular structures of 1–3 were unequivocally determined by single crystal X-ray diffraction, in which the tris(aromatic)phosphine coordinated to Fe resides in an apical position of the pseudo-square-pyramidal geometry. IR spectroscopy and X-ray crystallographic analysis for 1–3 have indicated that the highly electron rich tris(aromatic)phosphine ligands (where the corresponding electron-donating abilities display the following order of P(PhOMe-p)₃?>?P(PhMe-p)₃?>?P(PhF-p)₃) result in a considerable red shift of the CO-stretching frequencies and a clear change of the Fe–Fe bond distances in 1–3.     

The synthesis of N-substituted ureas II: Nucleophilic substitution of ureas at the carbonyl group

Summary N-Arylsubstituted ureas undergo exchange of the N-residue upon reaction with amines. Using kinetic measurements, investigation of product distribution, regioselectivity, catalysis, and substrate influences, it was shown that this reaction proceeds via a second order nucleophilic substitution at the urea carbonyl center. By means of semiempirical calculations using the MNDO method the alternative mechanism of fragmentation was investigated.

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Zur Synthese N-substituierter Harnstoffe II: Nucleophile Substitution von Harnstoffen an der Carbonylgruppe

Zusammenfassung N-Arylsubstituierte Harnstoffe erleiden bei der Reaktion mit Aminen einen Austausch des N-Restes. Durch kinetische Messungen, Untersuchung der Produktverteilung, Regioselektivität, Katalyse und des Einflusses des Edukts konnte abgeleitet werden, daß es sich hiebei um eine nucleophile Substitution zweiter Ordnung am Carbonylzentrum des Harnstoffs handelt. Durch semiempirische Rechnungen mit Hilfe der MNDO Methode wurde der alternative Reaktionsmechanismus einer Fragmentierung untersucht.

     

Study on the synthesis of 6-alkylaminouridines via the nucleophilic aromatic substitution reaction of 6-cyanouridine derivatives

6-Cyanouracil derivatives underwent direct substitution reactions with selective primary amines in the presence of N,N-dimethylaminopyridine as a catalyst to give the corresponding 6-alkylaminouracils. This reaction provides a facile access to versatile 6-alkylaminouridine derivatives.     

Activation of chlorine and fluorine by a phenylazo group towards nucleophilic aromatic substitution. Regioselective preparation of polysubstituted anilines

A phenylazo group was used for selective activation of ortho fluorine and chlorine atoms towards nucleophilic aromatic substitution with the propanethiolate anion. This enabled a regioselective synthesis of three substituted 4-alkoxyanilines. The regioselectivity of substitution was confirmed by comparison of experimental NMR chemical shifts with empirically predicted values. The observed reactivity of the substrates is discussed in the context of the substituent effect.     

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.     

Ortho-selectivity in the nucleophilic aromatic substitution (SNAr) reactions of 3-substituted, 2,6-dichloropyridines with alkali metal alkoxides

3-Substituted, 2,6-dichloropyridines have featured in the syntheses of small molecule inhibitors of a wide variety of biological targets. Hence, the regioselective displacement of the chlorines is of significant interest. Through conducting an extensive solvent study, we have found that non-polar, aprotic solvents of low hydrogen bond basicities favour substitution of the chlorine ortho to the 3-substituent by alkali metal alkoxides. We present convincing evidence that coordination of the alkali metal counter-ion to the 3-substituent (nitro, ester, amide) is the origin of the ortho-selectivity to give a cyclic, six-membered transition state. Excellent ortho-selectivities (?98:2) for secondary and tertiary alkoxides were realized with the sodium counter-ion, whereas the more reactive primary alkoxides required the harder, more Lewis acidic lithium counter-ion.     

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.     

Efficient synthesis of unsymmetrical diaryl thioethers via TBAF-mediated denitrative substitution of nitroarenes with PhSTMS under mild and neutral conditions

Tetrabutylammonium fluoride(TBAF) effectively facilitated a denitrative substitution reaction of electron-deficient nitroarenes with phenylthiotrimethylsilane(PhSTMS) under mild and base-free neutral conditions at room temperature,providing a practical and efficient synthesis of useful unsymmetrical diaryl thioethers.Nitroarenes bearing ortho-and para-positioned electron-withdrawing groups are the most reactive substrates,indicating that this reaction most possibly proceeded via the nucleophilic aromatic substitution(S_NAr) mechanism.