Products Of Nucleophilic Substitution Research Articles

Acyl Transfer Reactions of 2,4-Dinitrophenyl Furoates: Comparative Effects of Nucleophiles and Non-Leaving Groups

This study investigated the acyl group transfer reactions of 2,4-dinitrophenyl 5-substituted-2-furoates, promoted by 4-substituted phenoxides/phenols in a 20 mol% DMSO aqueous solution at 25 °C. The reactions yielded nucleophilic substitution products and displayed second-order kinetics, with βacyl values ranging from −2.24 to −2.50, ρ(x) values between 3.18 and 3.56, and βnuc values of 0.81 to 0.84. These findings indicate an addition–elimination mechanism where the initial step is rate-determining. Comparative analysis with previous data revealed that the transition state structure remained largely consistent when altering the non-leaving group from thienyl to furyl under similar conditions. Notably, a shift in the rate-determining step was observed when changing the nucleophile from secondary amines/ammonium ions to 4-substituted phenoxides/phenols, highlighting the significant impact of nucleophile selection on the reaction kinetics and mechanisms in acyl transfer reactions.

The study of the interaction of 1,2- and 1,4-naphthoquinones with aminophosphonic esters

A number of new biologically active phosphorus-containing quinones were prepared by the reaction of 2,3-dichloro-1,4-naphthoquinone and sodium 1,2-naphthoquinone-4-sulfonate with phosphonate nucleophilic reagents, aminophosphonic acid esters. The structures of the synthesized compoumds were confirmed by ESI-MS, 1H NMR, IR-spectroscopies and elemental analysis. It was shown that aminophosphonic esters form products of nucleophilic substitution of a chlorine atom of 1,4-naphthoquinone or a sulfonyl group of 1,2-naphthoquinone on an aminophosphonic fragment. The products of the interaction of sodium 1,2-naphthoquinone-4-sulfonate with primary aminophosphonates existed in solution in 1,2-quinoid or 2-hydroxy-1,4-quinonimine tautomeric form depending on pH. The antimicrobial activity of the prepared compounds was investigated against Escherichia coli В-906, Staphylococcus aureus 209-Р, Mycobacterium luteum В-917, Candida tenuis VKM Y-70 and Aspergillus niger VKM F-1119 strains by the method of diffusion in agar of their 0.1% and 0.5% solutions. 1,2-Naphthoquinone derivatives showed good activity against S. aureus at a concentration of 0.1%, in its turn 1,4-napthoquinone derivatives showed activity against M. luteum at a concentration of 0.5%.

Synthesis and reactions of allylic azides of the adamantane series

A mixture of nucleophilic substitution product and isomeric azide resulting from [3,3]-sigmatropic rearrangement was obtained by interaction of allyl bromides of adamantane series with sodium azide. Epoxidation reactions of allylic azides of the adamantane series were investigated. The reduction of the obtained trans -2-(adamantan-1-yl)-3-(azidomethyl)oxirane with lithium alumohydride synthesized ( S *)-(adamantan-1-yl)[( S *)-aziridin-2-yl]methanol which, when heated with hydrochloric acid, gives the product of the aziridine ring opening is (1 S *,2 R *)-1-(adamantan-1-yl)-3-chloro-1-hydroxypropan-2-amino chloride.

UNUSUAL TRANSFORMATIONS OF MONO- AND DISACCHARIDE INTERMEDIATES IN THE SYNTHESIS OF OLIGOSACCHARIDES RELATED TO FRAGMENTS OF THE CAPSULAR POLYSACCHARIDE OF <i>HAEMOPHILUS INFLUENZAE</i> TYPE E

In the course of the synthesis of oligosaccharides related to fragments of the capsular polysaccharide of Haemophilus influenzae type e, the transformations of various 2-O-trifluoromethanesulfonate derivatives of β-D-glucopyranosides in reactions with an azide anion was studied. It gives the products of both nucleophilic substitution and a rearrangement of the 6-membered pyranose ring with its contraction to the 5-membered one through (О-5–С-2)-cyclization. Their formation was interpreted for the first time using quantum mechanical calculations.

Computational Studies of Coinage Metal Anion M- + CH3X (X = F, Cl, Br, I) Reactions in Gas Phase.

We characterized the stationary points along the nucleophilic substitution (SN2), oxidative insertion (OI), halogen abstraction (XA), and proton transfer (PT) product channels of M− + CH3X (M = Cu, Ag, Au; X = F, Cl, Br, I) reactions using the CCSD(T)/aug-cc-pVTZ level of theory. In general, the reaction energies follow the order of PT > XA > SN2 > OI. The OI channel that results in oxidative insertion complex [CH3–M–X]− is most exothermic, and can be formed through a front-side attack of M on the C-X bond via a high transition state OxTS or through a SN2-mediated halogen rearrangement path via a much lower transition state invTS. The order of OxTS > invTS is inverted when changing M− to Pd, a d10 metal, because the symmetry of their HOMO orbital is different. The back-side attack SN2 pathway proceeds via typical Walden-inversion transition state that connects to pre- and post-reaction complexes. For X = Cl/Br/I, the invSN2-TS’s are, in general, submerged. The shape of this M− + CH3X SN2 PES is flatter as compared to that of a main-group base like F− + CH3X, whose PES has a double-well shape. When X = Br/I, a linear halogen-bonded complex [CH3−X∙··M]− can be formed as an intermediate upon the front-side attachment of M on the halogen atom X, and it either dissociates to CH3 + MX− through halogen abstraction or bends the C-X-M angle to continue the back-side SN2 path. Natural bond orbital analysis shows a polar covalent M−X bond is formed within oxidative insertion complex [CH3–M–X]−, whereas a noncovalent M–X halogen-bond interaction exists for the [CH3–X∙··M]− complex. This work explores competing channels of the M− + CH3X reaction in the gas phase and the potential energy surface is useful in understanding the dynamic behavior of the title and analogous reactions.

Preparation, Structure, and Reactivity of Pseudocyclic β‐Trifluorosulfonyloxy Vinylbenziodoxolone Derivatives

AbstractPseudocyclic β‐trifluorosulfonyloxy vinylbenziodoxolones were prepared starting from hydroxybenziodoxolones and alkynes in the presence of trifluoromethanesulfonic acid. The reaction of these compounds with azide anion leads to β‐azido vinylbenziodoxolones as products of vinylic nucleophilic substitution in which addition‐elimination reactions occur and the double bond configuration is retained. The structures of β‐trifluorosulfonyloxy vinylbenziodoxolone and β‐azido vinylbenziodoxolone were established by single crystal X‐ray diffraction.magnified image

A Fluorogenic and Chromogenic Probe Distinguishes Fluoride Anions and Thiols: Implications for Discrimination of Fluoride-Containing G Series and Sulfur-Containing V Series Nerve Agents.

A coumarin-based probe, FP2, was designed for the differential detection of fluoride anions and thiols, i.e., the corresponding nucleophilic substitution products from fluorine-containing G agents and sulfur-containing V agents, thus having the potential to discriminate between these two nerve agents. FP2 with two functional reaction groups, α, β-unsaturated ketone and silyl groups, can react selectively with fluoride anions and thiols at the μM level respectively. Intriguingly, in the THF solution, FP2 reacts with the fluoride anion but not with the thiol, whereas in the EtOH/HEPES solution, FP2 reacts with the thiol but not with the fluoride anion. As a result, FP2 can produce different fluorophores in the two detection solutions, thus displaying significant fluorescence changes. In addition, the FP2 detection system can show a significant color change from colorless to yellow within seconds when detecting fluoride anions in THF detection solutions, and from yellow to light blue when detecting thiols in EtOH/HEPES solutions, which will facilitate visual detection by emergency responders at the scene of an incident involving a nerve agent.

Aromatic nucleophilic substitution: A case study of the interaction of a lithiated nitronyl nitroxide with polyfluorinated quinoline-N-oxides

A 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl lithium derivative was found to react with 5,6,7,8-tetrafluoro- or 5,7,8-trifluoro-6-(trifluoromethyl)quinoline-N-oxides with the formation of products of aromatic nucleophilic substitution of the H atom at position 2 of the quinoline ring. The reaction regioselectivity is supported by the data of quantum-chemical calculations. Molecular and crystal structures of the obtained nitronyl nitroxides were solved by monocrystal X-ray diffraction analysis, and the nature of the radical was ascertained by electron spin resonance spectroscopy. Heterospin complexes of Cu(hfac)2 with the synthesized quinoline-substituted nitronyl nitroxides were prepared. According to X-ray diffraction analysis, seven-membered metallocycles are formed in the complexes owing to simultaneous coordination of the nitroxyl and N-oxide groups by the Cu atom.

INTERACTION OF α-CARBANIONS OF LITHIUM ACYLATES WITH 1,2-DIBROMOALKANES

We have studied the interaction of α-carbanions of lithium acylates with 1,2-dibromoalkanes with different length of the carbon chain in order to establish the direction of the reaction. Interaction of α-carbanions of lithium acylates obtained by metallation of acetic, butyric and isobutyric acids with lithium diisopropylamide and 1,2-dibromoalkanes (1,2-dibromohexane, 1,2-dibromoheptane or 1,2-dibromononane) with a molar ratio of reactants equal to 1: 2: 1 in argon atmosphere in tetrahydrofuran under normal conditions (20-25 °C) for 2 h leads to the products of the oxidative coupling of enolate anions: succinic acid, 2,3-diethylsuccinic acid (mixture of diastereomers of meso- and (±) -form in a ratio of ~ 2: 1) and 2,2,3,3-tetramethylsuccinic acid with 10-70% yields. We didn’t observe any products of sequential nucleophilic substitution in reaction. The yields of dicarboxylic acids depend on the structure of the initial α-carbanion of lithium acylate and on the carbon chain length of 1,2-dibromoalkane involved in the reaction. We established that the oxidative coupling proceeds most effectively in the interaction of 1,2-dibromoalkanes with an α-carbanion containing an anionoid center at the secondary α-carbon atom - α-carbanion of lithium butyrate (2,3-diethylsuccinic acid yields are 31-70%). We suggested the most probable anion-radical scheme of the formation of the products of the oxidative coupling of α-carbanions of lithium acylates through electron transfer from the enolate anion to 1,2-dibromoalkane with the generation of its radical anion. The pathways for the formation of primary bromoalkanes (1-bromohexane, 1-bromoheptane, 1-bromononane) and terminal olefins (hexene-1, heptene-1, nonene-1) that are generated from the corresponding 1,2-dibromoalkanes during the elimination of their radical anions with the loss of the bromine anion and the subsequent stabilization of 1-bromoalkyl radicals by abstraction of the hydrogen atom from the solvent, or by bromine elimination, are shown.

Some Features of the Reaction of 6-Methyl-2S-substituted Pyrimidin-4-ols with the Vilsmeier–Haack Reagent

Formylation of 6-methyl-2S-substituted pyrimidin-4-ols under the conditions of the Vilsmeier–Haack reaction leads to the formation of nucleophilic substitution products of the hydroxyl group. The formation of the expected formylation products does not occur.

Synthesis and Selected Reactions of 2(3)-Furoyl Phosphonates Functionalyzed at the Neighbor Position of the Furan Ring

Reactions of 2-and 3-furoyl chlorides having chloromethyl or butylthiomethyl group in the adjacent position of the furan ring as well as of analogous N-morpholinomethylfuroyl chloride hydrochlorides with triethyl phosphite have been studied. The synthesized chloromethylfuroyl phosphonates have given the corresponding products of nucleophilic substitution in the reactions with sodium azide and potassium thiocyanate in the case of 4-chloromethyl-3-furoyl phosphonate. In the reaction of 3-chloromethyl-2-furoyl phosphonate with sodium azide, cleavage of the P-C bond takes place simultaneously with nucleophilic substitution. Potassium thiocyanate forms 3-thiocyanatomethyl-2-furoyl phosphonate in the reaction with this substance. The synthesized stable furoyl phosphonates enter the Wittig reaction with resonance-stabilized phosphoranes to give phosphorylated furylalkenes. If these compounds carry a chloromethyl group in the furan ring, they react with sodium azide and potassium thiocyanate to give the corresponding products of nucleophilic substitution. Analogously, aminomethyl derivatives have been obtained in the reaction with morpholine at room temperature.

Naphthalimide-sulfonamide fused dansyl-sulfonamide fluorescent probe for tracking glutathione of lysosome with a dual-emission manner

Developing glutathione-specific fluorescent probes with novel fluorescence-responsive manners can enrich the applications of probes in living cells. In this work, we designed and synthesized a dual fluorophores (naphthalimide and dansyl) co-modified fluorescent probe, which displayed a high selectivity toward glutathione (GSH). In living cells, this probe could specifically visualize the GSH of lysosome and accompanied by two different fluorescence emissions. One is green emission that can be assigned to the nucleophilic substitution product (GSH-linked naphthalimide) while the other is orange emission that can be derived from the cleavage product (dansyl). Especially, such dual-emission bioimaging in living cells had a spatiotemporal and synchronous manner. It is expected to provide an alternative strategy for designing the functional fluorescent probes to be applied in multi-color bioimaging in future.

Nucleophilic substitution in nitroarenes: a general corrected mechanism

Nucleophilic substitution in electron-deficient arenes is one of the fundamental processes in organic chemistry; however, its mechanism as presented in textbooks does not adequately describe the process. According to this generally accepted mechanism, it is limited to substitution of halogens via nucleophilic addition at positions occupied by halogens. The possibility of addition at positions occupied by hydrogen is totally ignored. Research papers have shown that nucleophilic addition at positions occupied by hydrogen is a fast and reversible process, and σH adducts are initially formed as intermediates. These σH adducts can be converted into products of nucleophilic substitution of hydrogen in a few different ways or dissociate so that substitution of halogen can proceed. This general picture is confirmed by many examples presented.

New Synthesis of 2-Oxoalkanamide Oximes

Reactions of α-halocarboxylic acid amides with 3 equiv of hydroxylamine hydrochloride in the presence of bases involves formation of products of nucleophilic substitution of the halogen atom and their subsequent oxidation to the corresponding oximes. This one-pot transformation can be accomplished in various aprotic solvents or ethanol at 80°C. Dimethyl sulfoxide as solvent ensures the highest selectivity for the oxidation products. The yields of N-substituted 2-(hydroxyimino)carboxylic acid amides range from 22 to 92%.

Reactions of Substituted Indoles with 2,3-Dichloro-1,4-naphthoquinone and Electrochemical Properties of Some 2,3-Substituted 1,4-Naphthoquinones

The reactions of 2,3-dichloro-1,4-naphthoquinone with some indoles and thiols were investigated. The resulting nucleophilic substitution products were characterized by spectroscopic methods (FT-IR, 1H and 13C NMR, MS) and microanalysis. The effects of polar and nonpolar solvents on the electronic absorption spectra and electrochemical properties of some newly synthesized compounds were also studied.

Reactions of Lithium Acylates α-Carbanions with 1,2-Diiodoethane

The interaction of lithium acylates α-carbanions (obtained via metallation of acetic, butyric, and isobutyric acids with lithium diisopropylamide) with 1,2-diiodoethane under argon in tetrahydrofuran at 20–25°C has proceeded as oxidative cross-coupling of enolate anions to form succinic, 2,3-diethylsuccinic, and 2,2,3,3-tetramethylsuccinic acids with yields 50, 53, and 16%, respectively. The products of sequential nucleophilic substitution of iodine atoms with alkyloxycarbonyl species have not been detected.

Reactions of the N-isopropyl-α-chloroketimines with PIV dithioacids

A primary iminium salt formed in the reaction of PIV dithioacids with N-isopropyl-α-chloroketimines is transformed into products of nucleophilic substitution of the chlorine atom by dithiophosphorus group (SN pathway), if the imine carbon atom is bonded to the donor and small-volume methyl group, or undergoes reduction of the CCl bond (C-Cl→C-H) (Red pathway), when it is bonded with the bulky acceptor phenyl group. The same effect of substituents was discovered, when replacing methyl group with phenyl one in the position 2 of N-tert-butyl-2-chloraldimines: SN: Red ratio is 1: 0 in the case of Me and 1: 9 in the case of Ph. The iminium salts were transformed into new type ketones containing a phosphor functionality.

Regioselective Functionalization of the [ closo-1-CB9H10]- Anion through Iodonium Zwitterions.

Reactions of [ closo-1-CB9H9-1-R]- (2, R = H, COOH, C5H11) with PhI(OAc)2 lead to mixtures of regioisomers [ closo-1-CB9H8-1-R-6-IPh] (5[6]) and [ closo-1-CB9H8-1-R-10-IPh] (5[10]) in ratios of ∼3:1 to 1:1, of which the former isomer undergoes selective reactions with nucleophiles (MeCN, pyridine, MeC(═NH)NH2, CN-). The products and the unreacted 10-isomers 5[10] are separated achieving kinetic resolution of the isomeric iodonium zwitterions. Pure 5[10] is reacted with nucleophiles (pyridine, 4-C7H15OPyridine, Me2NCHS, PhCO2-, CN-, N3-, I-, MeC(═NH)NH2, and MeCN), giving substitution products. The mechanism of the substitution is investigated with density functional theory (DFT) methods. Some of the nucleophilic substitution products are transformed further, expanding the scope of available functional groups for the [ closo-1-CB9H10]- anion. Four derivatives are characterized with single-crystal XRD methods: [ closo-1-CB9H9-10-N2] (4[10]a), [ closo-1-CB9H9-6-NC5H5] (9[6]a), [ closo-1-CB9H9-10-NC5H5] (9[10]a), and [ closo-1-CB9H9-10-NHC(NH2)Me] (10[10]a). Spectroscopic data for selected derivatives are interpreted in terms of transmission of electronic effects through the { closo-1-CB9} cluster (NMR) and interaction with substituents (IR, UV). The latter results are compared to those of TD-DFT computational methods.

Modification of Polyfluoro-Containing 3-(Ethoxycarbonyl)flavones by Biogenic Amines and Amino Acids

Aim and Objective: The objective of our work was to study the peculiarities of transformations of fluorine-containing flavone-3-carboxylates with N-nucleophiles, including biogenic amines and amino acids. Materials and Methods: 6,7,8-Trifluoro and 5,6,7,8-tetrafluoroflavone-3-carboxylates were involved in interactions with a number of N-nucleophiles, such as pyrrolidine, morpholine, proline, arginine, gammaaminobutyric acid, beta-alanine, histamine, dopamine and amantadine under different reaction conditions. All synthesized compounds were characterized by NMR 1H, 19F, (NMR 13C for some compounds) and IR spectroscopic data, and elemental analysis. Results: 3-(Ethoxycarbonyl)polyfluoroflavones react with morpholine, pyrrolidine and L-proline to form 7- monosubstituted flavone-3-carboxylates. For the reactions of tetrafluoroflavone with pyrrolidine and morpholine, the formation of 5,7-disubstituted products is also possible. Interaction with gamma-aminobutyric acid leads to the 4-{[3-ethoxy-2-(2-hydroxypolyfluorobenzoyl)-3-oxo-1-phenylprop-1-enyl]amino}butanoic acids as a result of the pyrone ring opening. In reactions with dopamine, histamine, L-arginine and β-alanine, polyfluoroflavone-3-carboxylates underwent a chromone-coumarin rearrangement. 3-(Ethoxycarbonyl)tetrafluoroflavone forms with amantadine the nucleophilic aromatic substitution product, while trifluoro-substituted analog gives the chromone-coumarin rearrangement product. Conclusion: This work showed possibilities of chemical modification of polyfluorinated flavones in the reactions with amines depending on the structure of the nucleophilic reagent. Synthesized compounds are of interest for biological testing.

5-Amino-Substituted Derivatives of 4-Nitrofurazane: Synthesis, Structure, and Biological Activity

New amination reactions of 5-chloro-4-nitrobenzofurazane with different amines were studied. The reactions of 5-chloro-4-nitrobenzofurazane with 2,4,6-trichloro-, para-acetyl-, and para-carboxyethylanilines gave the products of aromatic nucleophilic substitution of the chlorine substituent in the nitrogenous heterocycle, the composition and structure of which was established by chemical, physical, and physicochemical methods and X-ray diffraction analysis. The thermal stability was studied by synchronous thermogravimetry and differential scanning calorimetry (TG‒DSC). The synthesized compounds showed a high antibacterial and antimycotic activity against human and animal pathogenic microflora.