Nucleophilic substitution of 4-bromomethyltriazolium with different nucleophiles

1,2,3-Triazolium salts draw much attentions in recent years. We developed a new synthetic method to heteroatom-functionalized triazoliums via nucleophilic substitution of 4-bromomethyltriazolium. This method afforded triazoliums with different S, N, and O heteroatom-substituents. Moreover, S_N2′ reaction was observed with alcohols or hydroxides. In addition, debromination and debromomethylation reaction occurred in some cases.     

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.     

Oxidative nucleophilic substitution of hydrogen in nitroarenes with phenylacetic acid derivatives

Oxidative nucleophilic substitution of hydrogen (ONSH) in nitroarenes with carbanion of isopropyl phenyl acetate gives various products depending on the conditions and oxidant. The reaction carried out in liquid ammonia and KMnO₄ oxidant gives iso-propyl α-hydroxy-α-nitroarylphenylacetates formed via hydroxylation of the initial ONSH products. In some cases additionally dimeric, trimeric and tetrameric products are formed. In THF and Bu₄N⁺MnO₄⁻ or DDQ oxidants simple ONSH products are formed whereas oxidation by dimethyl dioxirane (DMD) gave iso-propyl hydroxyaryl phenyl acetates. The dimeric and trimeric products are apparently formed via coupling of nitrobenzylic radicals generated in course of oxidation with nitrobenzylic carbanions of the ONSH products.     

Nucleophilic aromatic substitution reactions of fluorobenzenechromium complexes with P-chiral secondary phosphine-boranes: synthesis of optically pure P-chiral (dialkyl)arylphosphine-boranes

Optically pure P-chiral (dialkyl)arylphosphine-boranes having high structural diversity were prepared by two- or three-component coupling of fluorobenzenechromium complexes, P-chiral secondary phosphine-boranes, and other nucleophiles. The stereochemical integrity at the P-stereogenic center was completely retained during the S_NAr process when the reaction was carried out in THF at low temperature.     

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.

     

Nucleophilic substitution of ferrocenyl alcohols by cerium ammonium nitrate: C-N, C-S, and C-O bonds formation

Nucleophilic substitution of ferrocenyl alcohols with N-, S-, O-centered nucleophiles promoted by a catalytic amount of cerium ammonium nitrate (CAN) was studied. By this protocol, a series of second arylamine, thioether, and ether were facilely synthesized in moderate to good yields under mild conditions.     

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.     

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.     

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.     

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     

Nucleophilic substitution approach to 4′-substituted thymidines by employing 4′-benzenesulfonyl leaving group

Synthesis of 4′-substituted thymidines was investigated based on nucleophilic substitution using organosilicon and organoaluminum reagents. Two substrates having a benzenesulfonyl leaving group at the 4′-position were prepared for this purpose: 1-[4-benzenesulfonyl-3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-α-l-threo-pentofuranosyl]thymine (8α) and the 4′-(benzenesulfonyl)thymidine derivative (8β). The reaction of 8α with organosilicon reagents (Me₃SiCH₂CHCH₂ and Me₃SiN₃) in combination with SnCl₄ gave preferentially the 4′-substituted β-d-isomer: the 4′-allyl (12β) and 4′-azido (15β) derivatives, respectively. The reaction of 8α with AlMe₃, however, gave the 4′-methyl-α-l-isomer (16α) as the major product, presumably through an ion pair mechanism. By employing the substrate 8β in this reaction, the 4′-methylthymidine derivative (16β) was obtained exclusively in high yield. The 4′-ethyl (20β) and 4′-cyano (24β) derivatives were also synthesized by reacting 8β with the respective organoaluminum reagent.     

Nucleophilic substitution at an sp carbon of vinyl halides with an intramolecular thiolate moiety: synthesis of 2-alkylidenethietanes

Various 2-alkylidenethietanes were synthesized by intramolecular nucleophilic substitution reactions at an sp² carbon of vinyl halides with thiolate moieties. The reaction pathway of the substitution reactions was confirmed as a very rare S_NVπ mechanism by theoretical and experimental studies.     

1,2,4,5-Tetrazines: An intriguing heterocycles family with outstanding characteristics in the field of luminescence and electrochemistry

The 1,2,4,5-Tetrazines, or s-tetrazines, are a particular example of small, high nitrogen content heterocycle with extremely original physico-chemical properties. In this review, we summarize the last 20 years of research on this topic, focusing more on fluorescence and related optical properties on tetrazines, and tetrazine derived materials.     

Reactivity of cyclic sulfamidates towards lithium acetylides: synthesis of alkynylated amines

A synthetically useful level of reactivity of cyclic sulfamidates toward acetylides is described. Ring-opening reactions of a structurally diverse set of 1,2- and 1,3-cyclic sulfamidates with a range of lithium acetylides from aliphatic, cyclic, aromatic, heteroaromatic, and functionalized alkynes proceed smoothly in a regioselective manner to give the corresponding N-sulfate intermediates. Hydrolysis of these intermediates under acidic conditions furnishes the alkynylated amines in yields ranging from 29% to 98%. The scope of the acetylenic substitution reaction with the structural variations in both the cyclic sulfamidates and alkynes is briefly examined.     

Direct substitution of propargylic alcohol with oxygen, nitrogen, and carbon nucleophiles catalyzed by molybdenum(VI)

Efficient and direct substitution of propargylic alcohol with a variety of oxygen, nitrogen, and carbon nucleophiles catalyzed by MoO₂(acac)₂/NH₄PF₆ system was developed. The functional alkynes were obtained in modest to good yields with this versatile and practical protocol.     

Simple preparation of 7-alkylamino-2-methylquinoline-5,8-diones: regiochemistry in nucleophilic substitution reactions of the 6- or 7-bromo-2-methylquinoline-5,8-dione with amines

7-Alkylamino-2-methylquinoline-5,8-diones (7) were prepared from 6-bromo-2-methylquinoline-5,8-dione (2) not from 7-bromo-2-methylquinoline-5,8-dione (1). The chemistry of the transformation of 6-bromo-2-methylquinoline-5,8-dione (2) and various alkylamines, such as piperidine, 2-methylaziridine, benzylamine, n-butylamine, cyclohexylamine, t-butylamine, and ammonia, to 7-alkylamino compounds 7 as well as the transformation of 7-bromo compound 1 and the alkylamines to 6-alkylamino-2-methylquinoline-5,8-diones 11 was studied. The efficient and simple synthetic routes of the key intermediates, 6- and 7-bromo-2-methylquinoline-5,8-diones (2 and 1), from 5,8-dihydroxy-2-methylquinoline (15) and 5,7-dibromo-8-hydroxy-2-methylquinoline (9), respectively, were developed. We also proposed the mechanism for the unusual regioselectivity on the nucleophilic amination of 6- and 7-bromo-2-methylquinoline-5,8-diones (2 and 1).     

Nucleophilic substitution reaction at an sp carbon of vinyl halides with an intramolecular thiol moiety: synthesis of thio-heterocycles

This article presents a full account of intramolecular vinylic substitution reactions of bromoalkenes having an acetylthio moiety, which give sulfur-containing heterocycles such as dihydrothiophene, tetrahydrothiopyran, and 2-alkylidenethietane derivatives. The reaction pathways of the substitution reactions were investigated by theoretical and experimental studies.     

Polymer-supported protic functionalized ionic liquids for nucleophilic substitution reactions: superior catalytic activity compared to other ionic resins

Three polymer-supported quaternary ammonium mesylates were synthesized for recyclable polymeric phase transfer catalysts (PTCs). Through comparison study using nucleophilic fluorination, tertiary alcohol containing polymer 3c proved to be the best catalyst with high catalytic activity and chemoselectivity. It also exhibited not only superior activity in other nucleophilic substitution reactions, such as chlorination, bromination, iodination, acetoxylation, and azidation, but also good recyclability without any loss of catalytic activity or product yield.     

Spectroscopic studies of a BINAM-based sensor: Highly selective fluorescent recognition of lysine in water solution through a nucleophilic substitution reaction

A BINAM-based compound (R)-1 is found to show significant fluorescence enhancement in the presence of Lys in aqueous solution (1%DMF). This probe achieves highly selective fluorescent recognition of Lys even in the presence of other natural amino acids. It can be used as a sensitive as well as selective fluorescent probe for Lys. The mechanism for the interaction of (R)-1 with Lys was studied by NMR and HRMS.