Reaction Of Diazomethane Research Articles

MEDT study of the 1,3-DC reaction of diazomethane with Psilostachyin and investigation about the interactions of some pyrazoline derivatives with protease (Mpro) of nCoV-2

The molecular electronic density theory (MEDT) was invested to elucidate the chemo-, regio- and stereo-selectivity of the 1,3-dipolar cycloaddition between Diazomethane (DZM) and Psilostachyin (PSH). The DFT method at B3LYP/6-31 + G (d,p) level of theory was used. Reactivity indices, transition structures theory, IGM and ELF analysis were employed to reveal the mechanism of the reaction. The addition of DZM to PSH takes place through a one-step mechanism and an asynchronous transition states. Eight possible addition channels of reaction were investigated (addition of C (sp2) to Diazomethane at C4, C5, C6 or C7). The addition of C (sp2) at C5 leading to P1 product is the preferred channel. The addition of ether does not affect the chemo-, regio- and stereo-selectivity of the reaction. Analysis of transfer of charges along the IRC path associated with the P1 product shows a polar character for the studied reaction. We have also used the noncovalent interaction (NCI) which is very helpful to reveal the most favored addition channel of the reaction, by analyzing the weak interactions in different TSs. Finally, we investigate about the potential of inhibition of some pyrazoline compounds against COVID-19-Mpro by performing a molecular docking calculations.

Huisgen's 1,3‐Dipolar Cycloadditions to Fulvenes Proceed via Ambimodal [6+4]/[4+2] Transition States

AbstractHuisgen's 1960 announcement of the concept of 1,3‐dipolar cycloadditions was published the year before Alder's study of the reaction of diazomethane and dimethylfulvene. The diazomethane reaction was studied again in 1970 by Houk et al. and shown to give a [6+4] adduct. Padwa's nitrile ylide cycloaddition to dimethylfulvene (1978) gave [6+4] and [4+2] adducts. We performed computational studies of these reactions with density functional theory (DFT) and show that they involve ambimodal [6+4]/[4+2] transition states that can lead to either type of cycloadduct from one transition state. We dedicate this paper to the extraordinary life and humanity of Rolf Huisgen, and to the undying influence of his discoveries on chemistry.

Huisgen's 1,3-Dipolar Cycloadditions to Fulvenes Proceed via Ambimodal [6+4]/[4+2] Transition States.

Huisgen's 1960 announcement of the concept of 1,3-dipolar cycloadditions was published the year before Alder's study of the reaction of diazomethane and dimethylfulvene. The diazomethane reaction was studied again in 1970 by Houk et al. and shown to give a [6+4] adduct. Padwa's nitrile ylide cycloaddition to dimethylfulvene (1978) gave [6+4] and [4+2] adducts. We performed computational studies of these reactions with density functional theory (DFT) and show that they involve ambimodal [6+4]/[4+2] transition states that can lead to either type of cycloadduct from one transition state. We dedicate this paper to the extraordinary life and humanity of Rolf Huisgen, and to the undying influence of his discoveries on chemistry.

Dong-Pyo Kim.

"My biggest motivation is the happiness that comes from scientific discussions. For me, science is a tool of good communication in friendship, irrespective of age, language, or culture. Guaranteed to make me laugh is finding similarities in human nature and science …" Find out more about Dong-Pyo Kim in his Author Profile.

Lab-scale production of anhydrous diazomethane using membrane separation technology.

Diazomethane is among the most versatile and useful reagents for introducing methyl or methylene groups in organic synthesis. However, because of its explosive nature, its generation and purification by distillation are accompanied by a certain safety risk. This protocol describes how to construct a configurationally simple tube-in-flask reactor for the in situ on-demand generation of anhydrous diazomethane using membrane separation technology and thus avoiding distillation methods. The described reactor can be prepared from commercially available parts within ∼1 h. In this system, solutions of Diazald and aqueous potassium hydroxide are continuously pumped into a spiral of membrane tubing, and diazomethane is generated upon mixing of the two streams. Pure diazomethane gas diffuses out of the reaction mixture through the membrane tubing (made of gas-permeable Teflon AF-2400). As the membrane tubing is immersed in a flask filled with the substrate solution, diazomethane is instantly consumed, which minimizes the risk of diazomethane accumulation. For this protocol, the reaction of diazomethane with benzoic acid on a 5-mmol scale has been selected as a model reaction and is described in detail. Methyl benzoate was isolated in an 88-90% yield (597-611 mg) within ∼3 h.

Cycloaddition Reactions of the Phosphinidene-Bridged Complex [Mo2Cp(μ-κ1:κ1,η5-PC5H4)(CO)2(η6-HMes*)] with Diazoalkanes and Other Heterocumulenes.

The title phosphinidene complex reacted at room temperature with CS2 and SCNPh to give the phosphanyl derivatives [Mo2Cp{μ-κ2P,S:κ1S',η5-P(CS2)C5H4}(CO)2(η6-HMes*)] and [Mo2Cp{μ-κ2P,S:κ1P,η5-P(C(NPh)S)C5H4}(CO)2(η6-HMes*)], respectively (Mes* = 2,4,6-C6H2tBu3), which result from a [2 + 2] cycloaddition of a C═S bond in the organic reagent to the Mo═P bond of the phosphinidene complex, with further insertion of S into the remaining Mo-P bond, in the CS2 reaction. The title complex also reacted with diazoalkanes N2CRR' at room temperature to give the corresponding phosphaalkene derivatives [Mo2Cp{μ-η2:κ1P,η5-P(CRR')C5H4}(CO)2(η6-HMes*)] (CRR' = CH2, CPh2, CH(SiMe3)). These products follow from a formal [2 + 1] cycloaddition of the carbene CRR' fragment to the Mo═P bond of the parent compound but were shown to proceed through a [3 + 2] cycloaddition of the diazoalkane molecule, followed by N2 elimination. The diazomethane reaction allowed the identification at low temperature of a stabilized form of the intermediate product, the phosphanyl complex [Mo2Cp{μ-κ2P,N:κ1P,η5-P(CHN2H)C5H4}(CO)2(η6-HMes*)], which follows from a reversible 1,3-shift of a methylenic H atom from C to N. It was concluded that all of the above cycloaddition reactions are initiated by heteroatom coordination of the unsaturated organic molecule to the MoCp(CO)2 fragment in the parent phosphinidene complex, this triggering the P-C bond formation step which leads to the products eventually isolated. The structures of the new complexes were determined by spectroscopic, diffractometric, and (in some cases) density functional theory methods.

Reactions of Diazomethanes with 5‐Benzylidene‐3‐phenylrhodanine – A Computational Study

AbstractIt has been shown previously that the reaction of diazomethane with 5‐benzylidene‐3‐phenylrhodanine (1) in THF at −20° occurs at the exocyclic CC bond via cyclopropanation to give 3a and methylation to yield 4, respectively, whereas the corresponding reaction with phenyldiazomethane in toluene at 0° leads to the cyclopropane derivative 3b exclusively. Surprisingly, under similar conditions, no reaction was observed between 1 and diphenyldiazomethane, but the 2‐diphenylmethylidene derivative 5 was formed in boiling toluene. In the present study, these results have been rationalized by calculations at the DFT B3LYP/6‐31G(d) level using PCM solvent model. In the case of diazomethane, the formation of 3a occurs via initial Michael addition, whereas 4 is formed via [3+2] cycloaddition followed by N2 elimination and H‐migration. The preferred pathway of the reaction of 1 with phenyldiazomethane is a [3+2] cycloaddition, subsequent N2 elimination and ring closure of an intermediate zwitterion to give 3b. Finally, the calculations show that the energetically most favorable reaction of 1 with diphenyldiazomethane is the initial formation of diphenylcarbene, which adds to the S‐atom to give a thiocarbonyl ylide, followed by 1,3‐dipolar electrocyclization and S‐elimination.

Synthesis and ultrafast spectroscopic study of new [6,6]methanofullerenes

Ultrafast transient absorption and terahertz spectroscopic studies have been performed on new [6,6]methanofullerenes synthesized by the reaction of diazomethane with fullerene[60] via eco-friendly methodology, amine-assisted 1,3 dipolar cycloaddition (AACA).

Facile Synthesis of 2,4-Disubstituted Thiooxazoles and 2,4-Disubstituted Oxazole Sulfonyl Chlorides via Acyl Isothiocyanates and TMS-Diazomethane

An expedient method for the direct conversion of acyl isothiocyanates to 2,4-disubstitued thiooxazoles and 2,4-disubstituted oxazole sulfonyl chlorides is described. The method takes advantage of an early observation by Sheehan and the reaction of diazomethane with isocyanates to form oxazolones. However, in this case an acyl isothiocyanate is utilized as well as the readily available TMS-diazomethane to provide access to the desired 4-substituted sulfur derivatives. The 2,4-disubstituted oxazole systems synthesized represent novel thiooxazoles and oxazole sulfonyl chlorides not previously described.

A Solvent Effect in the Reaction of Diazomethane with Norbornane-2,3-dione 3-Hemiketals

A solvent effect in the reaction of diazomethane with norbornane-2,3-dione 3-hemiketal in various aprotic solvents such as ether, dichloromethane, tetrahydrofuran (THF), dioxane, and chloroform is reported. Unlike in methanol, preparatively useful quantities of oxetane derivatives were obtained along with a novel hexahydro-1H-cyclopenta[c]furan-1-one in these aprotic solvents. Dichloromethane and THF gave optimal yields of the two products. In some cases, α-ketoketals were formed as minor products along with the aforementioned products. Interestingly, TMSCHN2 furnished hexahydro-1H-cyclopenta[c]furan-1-one as the predominant product.

ChemInform Abstract: Unusual Reaction of Diazomethane with Stereoisomeric 3‐(Benzylcarbamoyl) ‐5,6,7,8‐tetrachloro‐1,4‐methano‐1,2,3,4‐tetrahydronaphthalene‐2‐carboxy lic Acids.

AbstractAttempts to convert cyclic amido acid (I) and its diastereomer (III) into corresponding amido esters by treatment with diazomethane result in the unexpected selective formation of corresponding dicarboxylic acid amides.

Unusual reaction of diazomethane with stereoisomeric 3-(benzylcarbamoyl)-5,6,7,8-tetrachloro-1,4-methano-1,2,3,4-tetrahydronaphthalene-2-carboxylic acids

Diazomethane is commonly used as efficient alkylating agent in the preparation of methyl esters and as a component in [2 + 3]-cycloaddition reactions [1]. However, there are no published data on dehydrating ability of diazomethane. With a view to accomplish cis–trans epimerization of cyclic amido acids I and II, an attempt was made to convert them into endo-cis and exo-cis amido esters III and IV by treatment with diazomethane in diethyl ether at 20°C. Unexpectedly, these reactions chemoselectively afforded the corresponding dicarboxylic acid imides V and VI, while even traces of esters III and IV were not detected. The structure of imides V and VI was confirmed by the H and C NMR spectra and independent synthesis from the corresponding anhydrides. It should be noted that known methods for the preparation of imides from amido acids require more severe conditions, in particular prolonged heating in high-boiling solvents (usually in DMF or Ac2O) in the presence of dehydrating agents [2]. rel-(1S,2R,3S,4R)-N-Benzyl-5,6,7,8-tetrachloro1,4-methano-1,2,3,4-tetrahydronaphthalen-2,3-dicarboximide (V). A solution of diazomethane in diethyl ether was added to a suspension of 0.9 g of amido acid I in diethyl ether until the mixture became homogeneous. The mixture was evaporated at 20oC, ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 10, pp. 1548–1549. © Pleiades Publishing, Ltd., 2013. Original Russian Text © S.A. Ismailov, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 10, pp. 1569–1570.

A Novel Series of 3,4‐Disubstituted Dihydropyrazoles: Synthesis and Evaluation for MAO Enzyme Inhibition

In this study, the authors have designed and synthesized a novel series of 3‐acyl‐4‐aryl‐4,5‐dihydropyrazoles, with the aim to obtain new potential scaffolds for the inhibition of both isoforms of monoamine oxidase (MAO) enzyme. The synthetic pathway to these compounds includes as a key step the 1,3‐dipolar cycloaddition reaction of diazomethane with a chalcone. All the compounds were fully characterized by means of spectroscopic and analytical data and showed specific inhibition against MAO A.

Smardaesidins A-G, isopimarane and 20-nor-isopimarane diterpenoids from Smardaea sp., a fungal endophyte of the moss Ceratodon purpureus.

Five new isopimarane diterpenes, smardaesidins A-E (1- 5) and two new 20-nor-isopimarane diterpenes, smardaesidins F (6) and G (7), together with sphaeropsidins A (8) and C-F (10-13) were isolated from an endophytic fungal strain, Smardaea sp. AZ0432, occurring in living photosynthetic tissue of the moss Ceratodon purpureus . Of these, smardaesidins B (2) and C (3) were obtained as an inseparable mixture of isomers. Chemical reduction of sphaeropsidin A (8) afforded sphaeropsidin B (9), whereas catalytic hydrogenation of 8 yielded 7-O-15,16-tetrahydrosphaeropsidin A (14) and its new derivative, 7-hydroxy-6-oxoisopimara-7-en-20-oic acid (15). The acetylation and diazomethane reaction of sphaeropsidin A (8) afforded two of its known derivatives, 6-O-acetylsphaeropsidin A (16) and 8,14-methylenesphaeropsidin A methyl ester (17), respectively. Methylation of 10 yielded sphaeropsidin C methyl ester (18). The planar structures and relative configurations of the new compounds 1-7 and 15 were elucidated using MS and 1D and 2D NMR experiments, while the absolute configurations of the stereocenters of 4 and 6-8 were assigned using a modified Mosher's ester method, CD spectra, and comparison of specific rotation data with literature values. Compounds 1-18 were evaluated for their potential anticancer activity using several cancer cell lines and cells derived from normal human primary fibroblasts. Of these, compounds 8, 11, and 16 showed significant cytotoxic activity. More importantly, sphaeropsidin A (8) showed cell-type selectivity in the cytotoxicity assay and inhibited migration of metastatic breast adenocarcinoma (MDA-MB-231) cells at subcytotoxic concentrations.

Continuous In Situ Generation, Separation, and Reaction of Diazomethane in a Dual‐Channel Microreactor

Continuous In Situ Generation, Separation, and Reaction of Diazomethane in a Dual‐Channel Microreactor

Continuous In Situ Generation, Separation, and Reaction of Diazomethane in a Dual‐Channel Microreactor

Ein bissiger Hund: Die bedarfsgesteuerte kontinuierliche In-situ-Erzeugung, Trennung und Reaktion von Diazomethan in einem Zweikanalmikroreaktor (siehe Bild; Diazald=N-Methyl-N-nitroso-p-toluolsulfonamid) ermöglicht die Durchführung zahlreicher Diazomethanreaktionen unter Vermeidung der gängigsten Probleme bei Herstellung, Handhabung, Transport und Zersetzung.

ChemInform Abstract: Synthesis and Reaction of Tributylstannylpyrazoles.

1,3-Dipolar cycloaddition reaction of diazomethane and ethyl diazoacetate with tributylstannyl-acetylenes occurred regioselectively to afford the corresponding 3(5)-tributylstannylpyrazoles. The cycloaddition reaction of 3-phenylsydnone with the stannylacetylenes proceeded also regioselectively, and 3-tributylstannyl-1-phenylpyrazoles were isolated. 4-Tributylstannyl- and 5-tributylstannyl-1-phenylpyrazole were prepared by the stannylation of 4-lithio- and 5-lithio-1-phenylpyrazoles with tributylstannyl chloride. Iodination, benzoylation, and phenylation of the stannylpyrazoles were examined

ChemInform Abstract: Diastereofacial Selectivity in 1,3-Dipolar Cycloadditions. Reactions of Diazomethane with endo,cis-5,6-Disubstituted Bicyclo(2.2.2)oct-2- enes.

Abstract The reaction of diazomethane with endo,cis-5,6-diacetoxy, dimesyloxy, bis(methoxycarbonyl) and dihydroxybicyclo[2.2.2]oct-2-ene derivatives, respectively, afforded either only the anti adduct or a mixture of anti and syn adducts wherein the anti diastereoisomer was highly dominant (10:1). The observed facial selectivity provides convincing evidence that direct through space interactions between the attacking 1,3-dipole and acetoxy, hydroxy etc. substituents are, as a whole, repulsive. Steric “non-bonded” repulsions and dipole-dipole interactions override possible stabilizing interactions, e.g. orbital interactions and hydrogen bonding effects.

Rhodamines NN: A Novel Class of Caged Fluorescent Dyes

A bright future: The reaction of diazomethane with acid chlorides obtained from N,N,N′,N′-tetraalkylrhodamines affords 2-diazo-2,3-dihydro-1H-indenespiro[1,9′]-9H-xanthen-3-ones—a novel class of caged rhodamines. These dyes allow new imaging procedures based on the step-wise activation and detection of several fluorescent markers (see picture).

DFT investigation on mechanism of dirhodium tetracarboxylate-catalyzed O-H insertion of diazo compounds with H2O

Abstract The mechanism of the dirhodium tetracarboxylate-catalyzed O-H insertion reaction of diazomethane and methyl diazoacetate with H2O has been studied in detail using DFT calculations. The rhodium catalyst and a diazo compound couple to form a rhodiumcarbene complex. Of two reaction pathways of the Rh(II)-carbene complex with H2O, the stepwise pathway is more preferable than the concerted one. Formation of a Rh(II) complex-associated oxonium ylide is an exothermal process, and direct decomposition of the ylide gives a very high barrier. The high barriers for the 1,2-H shift of Rh(II) complex-associated oxonium ylides make the ylides become stable intermediates in both reactions, especially for the reactions in solution. Difficulty in formation of a free oxonium ylide supports experimental results, indicating that the Rh(II) complex-catalyzed nucleophilic addition of a diazo compound proceeds via a Rh(II) complex-associated oxonium ylide rather than via a free oxonium ylide.