Showing papers on "Diazomethane published in 2020"

Addition reactions and diazomethane capture by the intramolecular P–O–B FLP: tBu2POBcat

Abstract: FLPs, R2POBcat (R = tBu 1, Mes 2), are readily derived from the reactions of the corresponding phosphine oxides, nBuLi and ClBcat. Despite the poor Lewis acidity of boron, these species react with PhOH, CO2, CS2, PhNCO, MesCNO, O2, 9,10-phenanthrenedione, and diazomethanes to effect FLP addition reactions affording a series of heterocycles. The reaction of 1 with EtO2CCHN2 gives the bicyclic product, EtO2CCHN2(tBu2POBcat)2. High-level DFT calculations reveal that these cyclization processes proceed via 1,1-addition to the terminal N of diazomethane followed by 1,2-boron-migration affording the five membered rings. The reaction of the EtO2CCHN2 derivative with the second equivalent of FLP 1 is attributed to less steric demands.

Insights into the mechanism and regiochemistry of the 1,3-dipolar cycloaddition reaction between benzaldehyde and diazomethane

Abstract: The 1,3-dipolar cycloaddition reaction of benzaldehyde with diazomethane is investigated, in gas phase and in diverse polar solvents, using the molecular electron density theory through density functional theory calculations at the B3LYP(+D3)/6-31G(d) level. Analysis of the reaction pathway reveals that this reaction takes place along a concerted but asynchronous mechanism. Computations show that the acetophenone product is kinetically and thermodynamically more favored than 2-phenylacetaldehyde product in agreement with experimental outcomes. The favored cyclization mode and the observed regioselectivity of this cycloaddition are rationalized by both activation energy calculations, frontier molecular orbital analysis and reactivity indices. Also, polar solvents effect favors the reaction. Furthermore, we performed electron localization function (ELF) topological analysis. The ELF topological analysis of diazomethane indicates that this reactant presents an allenic pseudoradical electronic structure.

Imidazotetrazines as Weighable Diazomethane Surrogates for Esterifications and Cyclopropanations

Abstract: Diazomethane is one of the most versatile reagents in organic synthesis, but its utility is limited by its hazardous nature. Although alternative methods exist to perform the unique chemistry of diazomethane, these suffer from diminished reactivity and/or correspondingly harsher conditions. Herein, we describe the repurposing of imidazotetrazines (such as temozolomide, TMZ, the standard of care for glioblastoma) for use as synthetic precursors of alkyl diazonium reagents. TMZ was employed to conduct esterifications and metal-catalyzed cyclopropanations, and results show that methyl ester formation from a wide variety of substrates is especially efficient and operationally simple. TMZ is a commercially available solid that is non-explosive and non-toxic, and should find broad utility as a replacement for diazomethane.

(3 + 2) cycloaddition reaction of 7-isopropylidenebenzonorbornadiene and diazomethane derivatives: A theoretical study

Abstract: The ability to synthesize targeted molecules hinges on detailed mechanistic insight of the reaction. The 1,3-dipolar cycloaddition reaction between diazomethane derivatives and 7-isopropylidenebenzonorbornadiene have been extensively studied using density functional theory (DFT) at the M06–2X/6-311G(d,p) level of theory in order to delineate the peri-, regio-, and stereo-selectivities of the reaction. The diazomethane is shown to periselectively add across the endocyclic olefinic bond of the 7-isopropylidenebenzonorbornadiene and stereoselectively in the exo fashion, yielding the exo-cycloadduct as the major product, with a rate constant of 3.83 × 104 s−1. The endo approach of this periselective path is the closest competing pathway with a rate constant of 8.78 × 101 s−1. Neither electron-donating groups (R = methyl, ethyl, amine, cyclopropyl) nor electron-withdrawing groups (R = cyano, nitro, carbonyl) on the diazomethane alters the peri- and stereo-selectivity of the reaction. However, the substituents do have an effect on whether the addition follow normal or inverse electron demand mechanisms. EDGs favor a normal electron demand mechanism while EWGs favor an inverse electron demand 1,3-dipolar cycloaddition reaction. While EDGs-substituted diazomethane derivatives behave as nucleophiles in reactions with 7-isopropylidenebenzonorbornadiene, EWGs-substituted diazomethane derivatives behave as electrophiles. The 1,3-dipole adds across the dipolarophile via a concerted asynchronous mechanism, but a stepwise diradical mechanism has been ruled out. The selectivities observed in the title reaction are kinetically controlled. Analysis of the nucleophilic Parr function ( P K − ) at the different reaction sites in the dipolarophile indicates that the diazomethane adds across the atomic centers with highest NBO and Mulliken atomic spin densities.

Atmospheric chemistry of diazomethane – an experimental and theoretical study

Abstract: The kinetics of the O3, OH and NO3 radical reactions with diazomethane were studied in smog chamber experiments employing long-path FTIR and PTR-ToF-MS detection. The rate coefficients were determi...

Synthesis of Cyclopropylmethyl Esters of Maleopimaric Acid and Diketocage Derivatives of Quinopimaric Acid by a Catalytic Reaction of the Corresponding Allyl Esters with Diazomethane

Abstract: A Pd(acac)2-catalyzed reaction of allyl esters of maleopimaric and diketocage quinopimaric acid derivative with diazomethane was studied for the first time with the aim to obtain cyclopropylmethyl derivatives of the pimaric acid series as potential pharmacologically active compounds. It was shown that the reaction proceeds under mild conditions and provides the desired cyclopropylmethyl derivatives in yields of 84–98%.

Synthesis of 2-(1,3-Diphenyl-1H-1,2,4-triazol-5-yl)-2,2-dinitroacetonitrile and Its Reaction with Diazomethane

Abstract: A method for the synthesis of 2-(1,3-diphenyl-1H-1,2,4-triazol-5-yl)-2,2-dinitroacetonitrile was developed, and its reaction with diazomethane was investigated to show the reaction involves 1,3-dipolar cycloaddition and forms a separable mixture of 4-[(1,3-diphenyl-1H-1,2,4-triazol-5-yl)dinitromethyl]-2H-1,2,3-triazoles. The latter react with KOH in ethanol to form potassium salts of 4-[(1,3-diphenyl-1H-1,2,4-triazole-5-yl)aci-nitromethyl]-1,2,3-triazoles.

Synthesis, characterization and biological activity of benzothiazoles derivatives

Abstract: In the present investigation 2-(hydrazinylmethyl)-1,3-benzothiazole was reacted with aryl aldehyde to give 2-{[2Z)-2-arylhydrazinyl]methyl}-1,3-benzothiazole (3a-f), which in absolute ethanol treated with thioglycolic acid (0001 mol) and anhydrous zinc chloride under reflux for 8 hr to get 3-[1,3-benzothiazol-2-ylmethyl) amino]-5-(aryl)-1,3-thiazolidin-2-ones (4a-f) On the other hand [Benzothiozole N-aryl thiozolemethanamines] (5a-f) were obtained, when the compounds (3a-f), are treated with diazomethane

Metabolites of the anaerobic degradation of diethyl ether by denitrifying betaproteobacterium strain HxN1.

Abstract: The constitutions of five metabolites formed during co-metabolic, anaerobic degradation of diethyl ether by the denitrifying betaproteobacterium Aromatoleum sp. strain HxN1 were elucidated by comparison of mass spectrometric and gas chromatographic data with those of synthetic reference standards. Furthermore, the absolute configurations of two stereogenic centers in the metabolites were established. Based on these results a degradation pathway for diethyl ether by Aromatoleum sp. HxN1 analogous to that of n-hexane is proposed. Synthesis of both enantiomers of methyl (E)-4-ethoxy-2-pentenoate was accomplished by etherification of ethyl (R)- or (S)-lactate, followed by hydrolysis of the ester group and reduction to furnish 2-ethoxy-1-propanol. The primary alcohol was converted by a Swern oxidation followed by a Horner-Wadsworth-Emmons reaction to methyl (E)-4-ethoxy-2-pentenoate that was finally hydrogenated to methyl 4-ethoxypentanoate. Methyl (S)-4-ethoxy-3-oxopentanoate was prepared by conversion of (S)-2-ethoxypropanoyl chloride with Meldrum's acid. Reduction of the resulting β-oxoester with NaBH4 or baker's yeast gave both diastereoisomers of methyl 4-ethoxy-3-hydroxypentanoate. The stereocenter at C-3 of the main diastereoisomer produced with baker's yeast was determined by Mosher ester analysis to be (R)-configurated. Dimethyl 2-(1-ethoxyethyl)succinate was prepared by Michael addition of nitroethane to diethyl maleate, followed by conjugate addition of sodium ethanolate, hydrolysis and esterification with diazomethane.

Method for preparing intermediate of 4-methoxypyrrole derivative

Abstract: The present invention relates to a method for preparing intermediates of 4-methoxypyrrole derivatives. The preparation method according to the present invention has advantages that a high-temperature reaction is not required as a whole, inexpensive and non-explosive reagents are used instead of (trimethylsilyl)diazomethane, and further an intermediate of 4-methoxy pyrrole derivatives can be prepared as a whole at a high yield.

DFT Study on the Mechanism of Iron-Catalyzed Diazocarbonylation.

Abstract: The mechanism of the carbonylation of diazomethane in the presence of iron–carbonyl–phosphine catalysts has been investigated by means of DFT calculations at the M06/def-TZVP//B97D3/def2-TZVP level of theory, in combination with the SMD solvation method. The reaction rate is determined by the formation of the coordinatively unsaturated doublet-state Fe(CO)3(P) precursor followed by the diazoalkane coordination and the N2 extrusion. The free energy of activation is predicted to be 18.5 and 28.2 kcal/mol for the PF3 and PPh3 containing systems, respectively. Thus, in the presence of less basic P-donor ligands with stronger π-acceptor properties, a significant increase in the reaction rate can be expected. According to energy decomposition analysis combined with natural orbitals of chemical valence (EDA–NOCV) calculations, diazomethane in the Fe(CO)3(phosphine)(η1-CH2N2) adduct reveals a π-donor–π-acceptor type of coordination.

Methylation of Quercetin by Diazomethane and Hypoglycemic Activity of its Tetra-O-Methyl Ether

Abstract: The tetra-O-methyl ether of quercetin (QU) 3 (54%), 3,7,4′-tri-O-methyl ether 4 (30%), and a previously unreported 3,7,3-tri-O-methyl ether of QU 5 (7%) were obtained via methylation of QU by an excess of diazomethane in dioxane. Their structures were established using 2D NMR (1H–1H COSY, 1H–1H NOESY, 1H–13C HSQC, 1H–13C HMBC). Tetra-O-methyl ether of QU 3 exhibited pronounced hypoglycemic activity, reduced alloxan-induced hyperglycemia in rats by 44.5% compared to a control, and was 2.7 times more active than QU.

Process of preparing diazomethane

Abstract: The present invention provides a process of preparing diazomethane. The process comprises: step S1, using N-methylurea as a raw material to continuously prepare a first product system containing N-methyl-N-nitrosourea in a continuous reactor; step S2, extracting and back-extracting the first product system continuously to obtain a N-methyl-N-nitrosourea solution; step S3, continuously reacting the N-methyl-N-nitrosourea solution with an alkali solution in a continuous reactor to obtain a second product system containing diazomethane; and step S4, continuously performing liquid separation and water removal by freezing on the second product system to obtain the diazomethane. A 2-methyltetrahydrofuran solution of MNU is obtained through a completely continuous reaction and posttreatment by using N-methylurea as a raw material, and then an anhydrous diazomethane solution is directly obtained through a completely continuous reaction and posttreatment. Water is removed by a freezing technology, and use of an expensive semipermeable membrane or liquid-liquid separator is avoided, so that the cost is lower.