Synthesis of 1-alkyl-3-arylamino-pyrrole-2,5-diones

Reaction of 1-alkyl-3-alkylaminopyrrole-2,5-diones with primary arylamine hydrochlorides in methanol or DMSO gives 1-alkyl-3-arylaminopyrrole-2,5-diones which could also be obtained from the reaction of arylaminofumarates with primary aliphatic amines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1001–1007, July, 2007.     

Nitropyrazoles. 11. Isomeric 1-methyl-3(5)-nitropyrazole-4-carbonitriles in nucleophilic substitution reactions. Comparative reactivity of the nitro group in positions 3 and 5 of the pyrazole ring

With reactions of isomeric 1-methyl-3-nitro- and 1-methyl-5-nitropyrazole-4-carbonitriles with anionic S-, O-, and N-nucleophiles (RSH, PhOH, and 3,5-dimethyl-4-nitropyrazole in the presence of K₂CO₃ or MeONa), it was shown that for N-substituted 3(5)-nitropyrazoles, the nitro group in position 5 is much more reactive than in position 3.     

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.     

Local chain configuration dependence of the mechanisms of analogous reactions of PVC. I. A conclusive study of the microstructure evolution in SN2 nucleophilic substitution

The nucleophilic substitution in poly(vinyl chloride) (PVC) with sodium benzenethiolate has been studied in two kinds of solvent differing in the molecular structure in the vicinity of the carbonyl group. From the evolution of the content of isotactic ( mm ), heterotactic ( mr ), and syndiotactic ( rr ) triads; and of mmmm, mmmr and rmmr isotactic pentads, in the unmodified parts of the polymer, as followed by ¹³C-NMR, it is unambiguously inferred that any chlorine but the central one of either the isotactic triad at mmr tetrads or the heterotactic triad at rmrr pentads is unreactive. Only a small fraction of mmr tetrads reacts occasionally by the central chlorine of its mr triad instead of the mm . Of those structures, the mmr , especially when located at the end of long isotactic sequences, proves to be highly reactive compared to the rmrr structure. By comparing quantitatively the microstructural changes with degree of substitution and taking into account that the reaction is of S_N2 type, the mechanisms of substitution through the three foregoing reactive chlorines have been stated. They are found to be independent of the type of solvent and to account for all the changes in triad and pentad content as experimentally found. Instead, the solvent dependence of the ratio between the mmr - and rmrr -based processes of substitution is such that the depletion of mmr compared to that of rmrr structure may be controlled. The conformational sensitivity of this behavior is discussed on the basis of side work in our laboratory. As a whole, the results of the present work provide some original concepts as to the role of the tacticity dependent microstructure and the related local conformations in the chemical reactions of PVC. © 1996 John Wiley & Sons, Inc.     

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).     

Preparation of poly(ether ketone)s derived from 2,5‐furandicarboxylic acid via nucleophilic aromatic substitution polymerization

From the viewpoint of the suppression of the petroleum consumption, aromatic poly(ether ketone)s (PEKs) were prepared by the nucleophilic aromatic substitution polymerization of 2,5‐bis(4‐fluorobenzoyl)furan (BFBF) synthesized from biomass and aromatic bisphenols. The model reaction of BFBF and p‐methoxyphenol revealed that BFBF possessed enough reactivity for the nucleophilic aromatic substitution reactions. The polymerizations of BFBF and aromatic bisphenols afforded high molecular weight polymers with good yields in N‐methylpyrrolidone and diphenyl sulfone for several hours. The longer polymerization time brought about the formation of insoluble parts in any solvents and reduction of molecular weight. The obtained PEKs were thermoplastics and exhibited good thermal stability, mechanical properties, and chemical resistance comparable to common high‐performance polymers. The thermal properties were tunable with the structure of bisphenols. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3094–3101     

The first nucleophilic aromatic substitution of suitably activated 2-methoxyfurans with Grignard reagents

The reaction of 2-methoxyfuroates 1 with Grignard reagents 2 leads to tertiary alcohols or S_NAr products depending on the position of the alkoxycarbonyl group. OMe-Displacement occurs only for 3-substituted derivatives. It takes place even for 3-acetyl-2-methoxyfuran while the presence of a further ester function at 4 position induces the formation of the sole 4-tertiary alcohol. The OMe-substitution has been verified for a wide range of furans and Grignard reagents and low yields have been found only in the reactions with the benzylic and allylic reagents which are delocalized anions. A mechanistic interpretation is given.     

Regiospecificity of nucleophilic substitution in 4,6-dinitro-1-phenyl-1H-indazole

The reactions of 4,6-dinitro-1-phenyl-1H-indazole with anionic nucleophiles RS^– and N₃ ^– lead to the regiospecific replacement of the nitro group at position 4. The reaction with N₂H₄·H₂O + FeCl₃ also results in reduction of only the 4-NO₂ group. Based on this fact, a procedure was developed for the preparation of previously unknown 3-unsubstituted 4-X-6-nitro-1-phenyl-1H-indazoles (X is a residue of a nucleophile or NH₂). Comparison of the data on the selective nucleophilic substitution (4-NO₂ group) in 3-Z-1-aryl-4,6-dinitro-1H-indazoles shows that in the case of Z = H, the regiospecificity of substitution is determined by the electronic effect of the annelated pyrazole ring.     

Intramolecular nucleophilic substitution at an sp carbon: synthesis of substituted thiazoles and imidazole-2-thiones

The nucleophilic substitution reactions of vinylic bromides with intramolecular thioamide or thiourea moieties proceed to give a series of substituted thiazoles and imidazole-2-thiones.     

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.     

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     

Reagents for specific modification of biopolymers 8. Synthesis of 2,7-diaminophenazinium salts by nucleophilic substitution of hydrogen

Direct nucleophilic substitution in quaternary 2-N-alkylacetamidophenazinium salts with primary and secondary amines can serve as a convenient method for the introduction of two different substituents under mild conditions.For part 7, see Ref. l.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 2059–2062, August, 1996.     

Vinylic nucleophilic substitution in functionalized 2-vinylpyrroles: a route to a new family of stable enols

2-(2-Cyano-1-ethylthioethenyl)pyrroles easy exchange their ethylthio group for hydroxyl (NaOH, H₂O-methanol, 40-45 °C, 1 h) to give 2-(2-cyano-1-hydroxyethenyl)pyrroles, a new family of stable enols, in 50-94% yields. The vinylic nucleophilic substitution proceeds at the double bond of both the starting pyrroles and their cyclic isomers, 3-iminopyrrolizines. X-ray structure analysis and NMR spectra show the enols to be stabilized by exceptionally strong intramolecular H-bonding.     

Separation of the enantiomers of 4-aryl-7,7-dimethyl- and 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones by chiral HPLC

Summary Analytical HPLC methods using derivatized cellulose chiral stationary phases have been developed for separation of the enantiomers of 25 racemic 4-aryl-7,7-dimethyl- or 1,77-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones, condensed derivatives of dihydropyrimidines. The enantiomers of the compounds were resolved by normal-phase chromatography on silica-based cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD) and amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD) columns with mobile phases consisting of mixtures ofn-hexane and an alcohol (2-propanol, ethanol, or methanol) in different proportions. The mobile phase and the chiral stationary phase were varied to achieve the best resolution. The effect of the concentration of alcohol in the mobile phase was studied. The resolution obtained on the two columns was complementary.     

Reinvestigation of the noncatalyzed coupling of aryllithium with haloarene: a novel aromatic nucleophilic substitution pathway

Noncatalyzed coupling reactions of aryllithiums and haloarenes proceed not only through the well-known aryne route but also, in some cases, through a novel addition-elimination pathway. Indeed, ortho-chloro- and ortho-bromomethoxyarenes lead selectively to the corresponding ortho-biaryls through a chelation-driven aromatic nucleophilic substitution pathway. Contrary to common belief, such noncatalyzed coupling reactions often proceed with high regioselectivity and high yield. These results underline the potency of such simple reactions and open up a straightforward access to a wide range of biaryl structures; this also appears particularly useful for large-scale and biaryl building-block syntheses, as only cheap and readily available substrates are involved.     

A domino protocol for the efficient synthesis of structurally diverse benzothiazolylquinoline-2,5-diones and their spiro analogues

Structurally diverse benzothiazolylquinoline-2,5-diones and their spiro analogues have been synthesized by an environmentally benign efficient and convenient synthetic method involving sulfamic acid catalyzed one-pot four-component reaction of Meldrum acid, 2-aminobenzothiazoles, dimedone, and isatin/carbonyl compound.     

The saddle point of the nucleophilic substitution reaction Cl− + CH3Cl: results of large-scale coupled cluster calculations

On the basis of large-scale coupled cluster calculations including connectedz triple substitutions in a perturbative way, the geometrical parameters of the D _{3 h} saddle point of the Walden inversion reaction Cl⁻ + CH₃Cl′→ ClCH₃ + Cl′⁻ are predicted to be R _s (C—Cl) = 2.301 ? and r _s (C—H) = 1.069 ?. The barrier height with respect to the reactants is recommended to be 11.5 ± 1.0 kJ mol⁻¹. Connected triple substitutions lower the barrier height by almost a factor of 2, but have very little influence on the geometric structure of the saddle point. Received: 26 June 1998 / Accepted: 15 July 1998 / Published online: 28 September 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.     

Nucleophilic substitution in 1-alkyl-4,5-dichloro-3-nitropyridazin-6-ones

Treatment of 1-alkyl-4,5-dichloro-3-nitropyridazin-6-one with C-nucleophiles and with ambident nucleophiles (2-azahetarylacetonitriles) leads to a selective substitution of a chorine atom by the quaternary carbon atom of the carbanion formed from a substituted acetonitrile. The pK_a of the CH-acid 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)malononitrile was determined by potentiometric titration. Reaction of 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)-2-hetarylacetonitriles with primary amines gives 6,7-dihydro-1H-pyrrolo[2,3-d]pyridazin-7-ones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 556–564, April, 2006.     

Unusual reactivity of 3-chloro-1-pentafluorosulfanylpropene in nucleophilic substitution reactions

Treatment of 3-chloro-1-pentafluorosulfanylprop-1-ene 1 with KCN yielded the product of prototropic rearrangement ClCHCHCH₂SF₅, whereas reactions with NaN₃ and KSCN gave the S_N2 products. Ab initio calculations at MP2/6-311++G** level are used to explain the unusual behaviour of cyanide. It was found that proton transfers from both 1 to CN⁻ and from HCN to the anion of 1 are exothermic. In contrast, azide and thiocyanate ions are too weakly basic to deprotonate 1.