An Under-Appreciated Source of Reproducibility Issues in Cross-Coupling: Solid-State Decomposition of Primary Sodium Alkoxides in Air

The decomposition of primary sodium alkoxide salts under ambient storage conditions and the effects of this phenomenon on commonly employed transition-metal-catalyzed cross-coupling reactions are described. By utilizing NMR, IR, and Raman spectroscopy, along with a modified Karl Fischer analysis, the main inorganic degradants were characterized, and CO₂ in the air was found to be a critical reactant within the decomposition process. The effects of storage conditions on decomposition were evaluated, and the preliminary experiments to understand the kinetics of this process were performed.

An Under-Appreciated Source of Reproducibility Issues in Cross-Coupling: Solid-State Decomposition of Primary Sodium Alkoxides in Air

The decomposition of primary sodium alkoxide salts under ambient storage conditions and the effects of this phenomenon on commonly employed transition-metal-catalyzed cross-coupling reactions are described. By utilizing NMR, IR, and Raman spectroscopy, along with a modified Karl Fischer analysis, the main inorganic degradants were characterized, and CO₂ in the air was found to be a critical reactant within the decomposition process. The effects of storage conditions on decomposition were evaluated, and the preliminary experiments to understand the kinetics of this process were performed.

Synthesis and Performances of Fatty Alcohol Polyoxyethylene Ether Sulfonate

Background: Fatty alcohol polyoxyethylene ether sulfonate (AESO) was synthesized by the following two steps reactions: fatty alcohol polyoxyethylene ether 5 (AEO-5) reacted with metallic sodium to form sodium alkoxide, then in toluene solvent, the sodium alkoxide reacted with 2-chloroethyl sulfonate sodium to form AESO. Methodology: The reaction factors, such as temperature, reaction time and reactant ratio, which effect on the product yield were discussed. The products were characterized by Fourier Transform Infrared (FTIR) spectra in order to examine the aim of the product synthesized. The AESO performances including thermal stability, salt resistance, emulsifying and surface properties were studied. Results: The results show that the optimum conditions of AESO synthesis are as follows: the reaction temperature is 64oC, the reaction time is 5h, the molar ratio of chloroethyl sulfonate sodium and sodium alkoxide is 1.2:1. In the above reaction conditions, the AESO has the highest yield, which is 74.43% and its purity is 89.25%. AESO’s surface properties, thermal stability, and salt resistance are much better than that of fatty alcohol polyoxyethylene ether sulfate (AES). The AESO presents the best emulsifying performance at the concentration of 1250mg/L. Conclusion: The solubility of AES and AESO are all increased due to the EO groups’ existence and their hard water resistances are better than that of lauryl sodium sulfate. The foamability test shows that AESO has the best foaming ability at the concentration of 1480mg/L, which decreases with the increase of the Ca2+ concentration, but the foam stability increases. It can be seen that AESO has favorable resistance to high temperature and high salinity.

Asymmetric α-Amination Reaction of Alkenoate Cyclic Esters Catalyzed by Chiral Tin Alkoxides

A catalytic enantioselective α-amination reaction of alkenoate cyclic esters with dialkyl azodicarboxylates was achieved by using a 3,3′-di(1-naphthyl)-substituted (R)-BINOL–dibromostannane complex as a chiral precatalyst in the presence of a sodium alkoxide and an alcohol. Optically active α-hydrazino ketones were obtained in moderate to high yields and with up to 91% ee in the presence of the chiral tin alkoxide generated in situ.

One-Pot Three-Component Synthesis of Pyrrolidin-2-ones via a Sequential Wittig/Nucleophilic Addition/Cyclization Reaction

A new efficient synthesis of pyrrolidin-2-ones via sequential Wittig reaction/nucleophilic addition/cyclization was developed. The Wittig reaction of the phosphoranes with isocyanates produced ketenimine intermediates that were then treated with primary amines to give amidines, which were treated with catalytic sodium alkoxide to give 2-imino-5-oxopyrrolidine-3-carboxylates in good yields.

An efficient and facile access to highly functionalized pyrrole derivatives

A straightforward and one-pot synthesis of pyrrolo[3,4-c]pyrrole-1,3-diones via Ag(I)-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with N-alkyl maleimide, followed by readily complete oxidation with DDQ, has been successfully developed. Further transformation with alkylamine/sodium alkoxide alcohol solution conveniently afforded novel polysubstituted pyrroles in good to excellent yields. This methodology for highly functionalized pyrroles performed well over a broad scope of substrates. It is conceivable that this efficient construction method for privileged pyrrole scaffolds could deliver more active compounds for medicinal chemistry research.

Palladium-Catalyzed Carbonylative Synthesis of Functionalized Benzimidazopyrimidinones

A new and convenient approach to functionalized benzimidazopyrimidinones is reported. It is based on a two-step procedure starting from readily available 1-(prop-2-yn-1-yl)-1H-benzo[d]imidazol-2-amines, consisting of a multicomponent palladium-catalyzed oxidative cyclocarbonylation–alkoxycarbonylation process, followed by base-promoted isomerization of the initially formed mixture of isomeric carbonylated products. Fair to good overall yields of the final alkyl 2-(2-oxo-1,2-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-3-yl)acetates are obtained, using different alcohols as solvent and nucleophile in the carbonylation step (carried out in the presence of 0.33–1 mol% PdI2 in conjunction with 17–50 mol% KI, at 100 °C and under 20 atm of a 4:1 mixture of CO–air) and the corresponding sodium alkoxide as base in the subsequent isomerization step (carried out in the alcoholic solvent at room temperature). The structures of a representative substrate [N-benzyl-1-(prop-2-yn-1-yl)-1H-benzo[d]imidazol-2-amine] and a representative product [methyl 2-(1-isopentyl-2-oxo-1,2-dihydrobenzo-[4,5]imidazo[1,2-a]pyrimidin-3-yl)acetate] were confirmed by X-ray diffraction analysis.

A direct and vicinal functionalization of the 1-methyl-2-quinolone framework: 4-alkoxylation and 3-chlorination

Bis(functionalization), 4-alkoxylation and 3-chlorination, of the 1-methyl-2-quinolone framework was achieved by a sequential treatment of 3-nitrated 2-quinolones with sodium alkoxide and NCS.