Presence Of 4-dimethylaminopyridine Research Articles

Derivatization procedure of estradiol with a combination of MPDNP-F and 4-dimethylaminopyridine to generate product ion containing estradiol-skeleton for reliable determination of its serum/plasma concentrations by LC/ESI-MS/MS

The quantification of serum/plasma estradiol (E2) is useful for the diagnosis, pathological analysis, and monitoring of the therapeutic efficacy of estrogen-dependent diseases. In this study, an improved derivatization method using 1-(2,4-dinitro-5-fluorophenyl)-4,4-dimethylpiperazinium iodide (MPDNP-F) was developed and combined with liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) for the sensitive and specific quantification of the serum/plasma E2. In the new method, the reaction time was reduced to 15 min from 90 min (two-step reaction in the previous method) by the direct reaction of MPDNP-F with E2 at 60°C in the presence of 4-dimethylaminopyridine (DMAP). DMAP served as the organic catalyst and had a less negative effect on the LC/ESI-MS/MS instrument compared to the non-volatile inorganic salt (NaHCO3), which was used in the previous method. The collision-induced dissociation of the molecular cation ([M]+) of the resulting derivative provided a product ion containing the E2-skeleton ([M–NO2–H]+), which significantly enhanced the assay sensitivity and specificity; compared to the dansyl chloride derivatization, which is the currently most-used derivatization procedure for the LC/ESI-MS/MS assays of E2, the MPDNP-F derivatization had significantly fewer interfering peaks and a clear and flat baseline in the serum sample analysis. The MPDNP-F derivatization–LC/ESI-MS/MS method enabled the precise and accurate quantification of E2 even at a 5.0 pg/mL concentration (lower limit of quantification) with a small sample volume (100 μL of serum/plasma) and had a tolerance for the matrix effect. This method was also proven to serve as a more sensitive and specific alternative to the clinically used chemiluminescence enzyme immunoassay.Graphical

Photoinduced Borylation of the Inert C(sp3)-O Bond of Alkyl Heteroaryl Ethers.

A photoinduced reductive Calkyl-O borylation of alkyl heteroaryl ethers with very negative reduction potential in the presence of 4-dimethylaminopyridine (DMAP) and bis(catecholato)diborane(B2cat2) was developed. Despite the high reducing power, various substrates with liable functional groups were well-tolerated as well as ethers derived from natural products and medicinal-relevant compounds. Mechanistic investigation implied that an intra-single electron transfer process in an electron donor-acceptor complex formed from ethers with the adduct of B2cat2 and DMAP should be involved.

Custom-modified oligolactide-cyclodextrin derivatives for electrospun drug formulations

Custom-synthesized cyclodextrin-oligolactide derivatives (CDLA) were used to produce electrospun nanofibers. The modified cyclodextrins were obtained through solution ring-opening oligomerization initiated by α-, β-, or γ-cyclodextrin in the presence of 4-dimethylaminopyridine. Following the NMR spectroscopy and mass spectrometry structural characterization, the CDLA derivatives are described as low molecular weight compounds having the lactate monomer units placed on the smaller rim of cyclodextrins as multiple short chains. The electrospinning (ESP) of the α-, β- and γ-CDLA homologous series was optimized for the use of high-concentration water/ethanol feed solutions. Scanning electron microscopy was employed for the morphology investigation of the nanofibrous webs, while the dynamic vapor sorption revealed the hygroscopicity changes induced through the ESP process. Further, the applicative potential was investigated by preparing α-, β- and γ-CDLA/curcumin nanofibrous webs. FTIR and NMR spectroscopy characterization, and thermogravimetric analysis were used to describe the particularities of curcumin association with CDLA in ESP process. The preservation of the curcumin antioxidative potential upon the ESP processing was tested, showing that β- and γ-CDLA/curcumin nanofibrous webs are better suited for curcumin formulations.

A Photochemical Protocol for the Synthesis of Weinreb and Morpholine Amides from Carboxylic Acids Cover Feature: (Eur. J. Org. Chem. 24/2023)

The Cover Feature illustrates the photochemical conversion of carboxylic acids to Weinreb and morpholine amides. Sunlight or LED 370 nm irradiation mediates the direct coupling of carboxylic acids to N,O-dimethylhydroxylamine or morpholine in the presence of 4-dimethylaminopyridine and bromotrichloromethane, providing the corresponding amides in satisfactory to high yields. More information can be found in the Research Article by C. G. Kokotos, G. Kokotos et al.

Atmosphere-controlled selective synthesis of ureas and thioureas from isothiocyanates

An atmosphere-controlled selective synthesis of ureas and thioureas from isothiocyanates in the presence of 4-dimethylaminopyridine is described. A series of disubstituted ureas and thioureas were prepared in air and nitrogen atmosphere, respectively. This protocol employs benign reagents and exhibits good chemoselectivity and practicality.

Synthesis of 2-Imino-1,3,4-oxadiazolines from Acylhydrazides and Isothiocyanates via Aerobic Oxidation and a DMAP-Mediated Annulation Sequence

In this work, an efficient synthesis of 2-imino-1,3,4-oxadiazolines from acylhydrazides and isothiocyanates is described. In the presence of 4-dimethylaminopyridine (DMAP) and molecular oxygen, various 2-imino-1,3,4-oxadiazolines were produced in good to high yields. The developed method showed a broad substrate scope and was effective on the gram scale. On the basis of the mechanistic studies and previous literature, it was proposed that the mechanism consists of an aerobic oxidation of acylhydrazides facilitated by DMAP and isothiocyanates, followed by a DMAP-mediated annulation of the in situ generated acyldiazenes with isothiocyanates.

4-Dimethylaminopyridine-catalyzed synthesis of isothiocyanates from amines and carbon disulfide

Isothiocyanates were synthesized by reactions between primary amines and CS2 in the presence of 4-dimethylaminopyridine as a catalyst and tert-butyl hydroperoxide as an oxidant. Various aryl, benzyl, alkyl, and hydroxyl amines were transformed into the corresponding isothiocyanates in 41–82% yields.

Photophysical Studies on Drug Conjugates of Stavudine/Zidovudine and 1,8-Naphthalimide in Different Solvent Systems

A number of fluorescent conjugates of popular anti-HIV drugs 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine, d4T) and 3′-azido-3′-deoxythymidine (zidovudine, AZT) with 1,8-naphthalimide were synthesized using the coupling reagent dicyclohexylcarbodiimide (DCC) in the presence of 4-dimethylaminopyridine (DMAP) and N,N-dimethylformamide (DMF) as solvent at room temperature. The steady-state fluorescence measurement studies on these conjugates showed solvatochromic effect. Further, the fluorescence of drug conjugates was recorded in the presence of ions like Na+ and K+ at body level concentration of 135-145 mmol L-1 and 3.6-5.1 mmol L-1, respectively, in phosphate buffer at pH 7.4 in aqueous media. It was observed that the drug conjugates did not show appreciable fluorescence quenching in presence of ions and buffer.

Synthesis of Tosyl- and Nosyl-Ended Polyisobutylenes with High Extent of Functionalities: The Effect of Reaction Conditions.

Endfunctional polymers possess significant industrial and scientific importance. Sulfonyl endgroups, such as tosyl and nosyl endfunctionalities, due their ease of substitution are highly desired for a variety of polymer structures. The sulfonylation of hydroxyl-terminated polyisobutylene (PIB-OH), a chemically and thermally stable, biocompatible, fully saturated polymer, with tosyl chloride (TsCl) and nosyl chloride (NsCl) is presented in this study. PIB-OHs derived from commercial exo-olefin-ended PIB (PIBexo-OH) and allyl-terminated polymer made via quasiliving carbocationic polymerization of isobutylene (PIBall-OH) were tosylated and nosylated in the presence of 4-dimethylaminopyridine (DMAP), pyridine and 1-methylimidazole (1-MI) catalysts and triethylamine (TEA). Our systematic investigations revealed that the end product distribution strongly depends on the relative amount of the components, especially that of TEA. While PIBexo-OTs with quantitative endfunctionality is readily formed from PIBexo-OH, its nosylation is not as straightforward. During sulfonylation of PIBall-OH, the formed tosyl and nosyl endgroups are easily substituted with chloride ions, formed in the first step of sulfonylation, leading to chloride termini. We found that decreased amounts of TEA afford the synthesis of PIBall-OTs and PIBall-ONs with higher than 90% endfunctionalities. These sulfonyl-ended PIBs open new ways for utilizing PIB in various fields and in the synthesis of novel PIB-containing macromolecular architectures.

Organocatalytic Regioselective [3+2] Annulation of Morita-Baylis-Hillman Carbonates with Azonaphthalenes: An Efficient Access to 3-Spiropyrazole- 2-oxindoles

Background: A cheap and commercially available organocatalyst, 4-dimethylaminopyridine was successfully employed in the regioselective [3+2] cycloaddition of isatin-derived Morita-Baylis- Hillman carbonates with azonaphthalenes for the construction of 3-spiropyrazole-2-oxindoles in excellent yields under mild conditions. Methods: In the presence of 4-dimethylaminopyridine with a loading of 10 mol%, a series of isatinderived Morita-Baylis-Hillman carbonates reacted smoothly with azonaphthalenes in dichloromethane at room temperature to furnish 3-spiropyrazole-2-oxindoles in 72-98% yield. Result and Conclusion: In summary, we have developed reasonably cheap and commercially available 4-dimethylaminopyridine-mediated regioselective [3+2] annulations between isatin-derived Morita- Baylis-Hillman carbonates and azonaphthalenes for the construction of 3-spiropyrazole-2-oxindoles under mild conditions.

POCOP-type cobalt and nickel pincer complexes bearing an appended phosphinite group

The reaction of 1,3,5-(iPr2PO)3C6H3 with Co2(CO)8 leads to the isolation of a POCOP-type mononuclear pincer complex {κP,κC,κP-2,4,6-(iPr2PO)3C6H2}Co(CO)2 (1) or a tetranuclear species {κP-{κP,κC,κP-2,4,6-(iPr2PO)3C6H2}Co(CO)2}2Co2(CO)6 (2), depending on the ligand to cobalt ratio employed. The latter compound can be an impurity during the synthesis of {2,6-(iPr2PO)2-4-Me2N-C6H2}Co(CO)2, when the ligand precursor 5-(dimethylamino)resorcinol is contaminated with phloroglucinol due to incomplete monoamination. Similarly, the reaction of 1,3,5-(iPr2PO)3C6H3 with NiCl2 in the presence of 4-dimethylaminopyridine provides {κP,κC,κP-2,4,6-(iPr2PO)3C6H2}NiCl (3) bearing an appended phosphinite group. Structures 1–3 have been studied by X-ray crystallography.

DMAP-Catalyzed One-Pot Synthesis of Quinazoline-2,4-diones from 2-Aminobenzamides and Di-tert-butyl Dicarbonate.

The one-pot synthesis of quinazoline-2,4-diones was developed in the presence of 4-dimethylaminopyridine (DMAP) by metal-free catalysis. The commercially available (Boc)2O acted as a key precursor in the construction of the 2-position carbonyl of quinazolinediones. The p-methoxybenzyl (PMB)-activated heterocyclization could smoothly proceed at room temperature instead of the microwave condition. This strategy is compatible with a variety of substrates with different functional groups. Furthermore, this protocol was utilized to smoothly prepare Zenarestat with a total yield of 70%.

A facile access to N-sulfonylthioimidates and their use for the transformation to 3,4-dihydroquinazolines.

N-Sulfonylthioimidates can be efficiently synthesized through one-pot three-component coupling of terminal alkynes, sulfonyl azides, and thiols by using a copper(i) catalyst in the presence of 4-dimethylaminopyridine. The proposed reaction is characterized by mild reaction conditions and tolerance of diverse functional groups. Additionally, the crucial pharmacophore of 3,4-dihydroquinazolines was synthesized using a one-pot synthetic strategy from N-sulfonylthioimidates.

Transesterification of Exocyclic Ester Group of Methyl Pheophorbide a

The reaction of methyl pheophorbide a with various alcohols in toluene in the presence of dimethylaminopyridine as a base was investigated. Under these conditions, a chemoselective transesterification of the exocyclic ring proceeds without the use of an activating agent (N-methyl-2-chloropyridinium iodide) or a catalyst (molecular iodine).

Activations of all Bonds to Silicon (Si-H, Si-C) in a Silane with Extrusion of [CoSiCo] Silicide Cores.

The [BP3 iPr]Co(I) synthon Na(THF)6{[BP3 iPr]CoI} (1, [BP3 iPr] = κ3-PhB(CH2P iPr2)3-) reacts with PhSiH3 or SiH4 to form unusual {[BP2 iPr](SiH2R)CoH2}═Si═{H2Co[BP3 iPr]} species (R = Ph, 2a; R = H, 2b; [BP2 iPr] = κ2-PhB(CH2P iPr2)2) that result from activation of all Si-H and Si-C bonds in the starting silanes. Solution-spectroscopic data (multinuclear NMR, IR) for 2a,b, and the solid-state structure of 2a, indicate substantial Co═Si═Co multiple bonding and minimal interaction of the core Si atom with nearby hydride ligands. In the presence of 4-dimethylaminopyridine (DMAP), 1 reacts with PhSiH3 to give [BP3 iPr](H)2CoSiHPh(DMAP) (3). Complexes 2a,b eliminate RSiH3 upon thermolysis in the presence of DMAP to generate {[BP2 iPr]Co(NC5H3NMe2)}═Si═{H2Co[BP3 iPr]} (4).

Copper-Catalyzed Double Thiolation To Access Sulfur-Bridged Imidazopyridines with Isothiocyanate.

A copper(I)-catalyzed sulfur-bridged dimerization of imidazopyridines has been developed using isothiocyanate as the sulfur source. This method enables a switchable synthesis of bis(imidazo[1,2- a]pyridin-3-yl)sulfanes or bis(2-(imidazo[1,2- a]pyridin-2-yl)phenyl)sulfanes in the presence of 4-dimethylaminopyridine (DMAP) or K2CO3 when different imidazopyridines were employed. Under optimized conditions, a variety of sulfur-bridged imidazopyridines were obtained in good yields. Moreover, thiourea was proved to be the key intermediate under catalytic system A.

Synthesis, Transformations and Characterization of 8 Aminomethyl Substituted Umbelliferones as Probable Anti-Arrhythmic Agents

Background: Coumarin and modified nitrogen heterocyclic nuclei show biological activity. Combining these into a hybrid molecule could lead to new pharmacological agents. A series of hybrid compounds combining coumarin and piperidine, piperazine, purine or tetrahydroisoquinoline moieties were synthesized and evaluated for anti-arrhythmic activity. Methods: The Mannich reaction of coumarins (peurutenicin, peucenol and 6-cyanoumbelliferrone) with formaldehyde and various amines, including several alkaloids – anabasine, theophylline or tetrahydroisoquinolines, proceeds by heating under reflux in dioxane in the presence of 4-dimethylaminopyridine. The Suzuki reaction of 6,8-disubstituted umbelliferone triflate was used for the introduction of an aryl substituent in position 7 of the the coumarin framework. Results: Twenty two novel coumarin-based Mannich bases were synthesized via introduction of functional aminomethyl group at position 8 of 6 substituted 7-hydroxy-2H-chromen-2-ones by Mannich reaction. The results illustrated that the C-6 and C-8 substituents’ effect was obvious in our designed system and there was a relationship between the structures and the anti-arrhythmic activity of the 6,7,8- trisubstituted coumarins. 8-(6,7-dimethoxy-1-(3,4,5-trimethoxyphenyl)-tetrahydroisoquinolinylmethyl)- substituted peucenol derivatives shown in vivo a pronounced and selective anti-arrhythmic activity on epinephrine arrhythmias in comparison with natural coumarin peucenol. The moderate toxicity of the new compound encouraged further design of therapeutically relevant analogues based on this novel type of coumarin- tetrahydroisoquinoline hybrids. Conclusion: We have developed a mild reaction protocol to synthesize new mannich products on the basis of substituted coumarins. The anti-arrhythmic activity of coumarin-tetrahydroisoquinoline hybrids was revealed. We report for the first time that coumarin containing 8-(1-(3,4,5-trimethoxyphenyl) tetrahydroisoquinolinyl)methyl) substituent offer a suitable scaffold for the development of novel anti-arrhythmic agents.

Screening commercial available resins for simultaneous removal of two potential genotoxins from API methanolic streams

ABSTRACTThis paper explores potential API loss mitigation during purification in recrystallization mother liquors, by including a resin adsorption step, to remove potential genotoxin impurities (PGTIs). Mometasone furoate (Meta) is used as model active pharmaceutical ingredient (API) in the presence of 4-dimethylaminopyridine (DMAP) and methyl p-toluenesulfonate (MPTS) as two model PGTIs. AG 50W-X2 and IRA68 resins efficiently removed DMAP and MPTS from methanol solutions, respectively, with adsorptions higher than 93% and Meta binding below 2%. Removal of GTIs using these resins sequentially, or combining them in a single step, was also assessed, with superior results for the later approach.Abbreviations: API, active pharmaceutical ingredient; DMAP, 4-dimethylaminopyridine; DMAP-Me, methylated DMAP; GTI, potential genotoxin impurity; Meta, Mometasone furoate; MPTS, methyl p-toluenesulfonate; PTSA, p-toluenesulfonic acid; TTC, threshold of toxicological concern.

Greening the Solid-Phase Peptide Synthesis Process. 2-MeTHF for the Incorporation of the First Amino Acid and Precipitation of Peptides after Global Deprotection

In solid-phase peptide synthesis, dichloromethane is the predominant solvent used to incorporate the first amino acid on a 2-chlorotrityl chloride resin (via nucleophilic substitution) and Wang resin (via activation with carbodiimide in the presence of 4-dimethylaminopyridine). However, legal authorities have restricted the use of this solvent, as it is considered hazardous and a potential occupational carcinogen. Therefore, there is a need for an alternative that is easy to handle and poses less risk for the environment and more importantly for human health. Herein, we describe 2-methyltetrahydrofuran as a greener alternative for the incorporation of the first protected amino acids on both 2-chlorotrityl chloride and Wang resins. The amounts of several amino acids loaded on 2-chlorotrityl chloride and Wang resins using dry dichloromethane or 2-methyltetrahydrofuran were comparable. In addition, the use of 2-methyltetrahydrofuran rendered acceptable racemization and dipeptide formation in the case of Wang...

Silylene Complexes of Late 3d Transition Metals Supported by tris-Phosphinoborate Ligands

The complexes [BP3R]MX ([BP3R] = PhB(CH2PR2)3–, R = Ph, iPr; M = Ni, Co, Fe; X = halide) were explored as platforms for generation of first-row metal silylene complexes. Direct silylation of [BP3Ph]NiCl or [BP3iPr]CoCl with (THF)2LiSiHMes2 resulted in formation of the silylene complexes [BP3Ph]Ni(μ-H)(SiMes2) and [BP3iPr]Co(μ-H)(SiMes2), respectively. In contrast, [BP3iPr]FeBr reacted with (THF)2LiSiHMes2 to produce the iron-alkyl [BP3iPr]Fe(CH2-2-(SiH2Mes)-3,5-Me2C6H2), a constitutional isomer of the expected silyl or silylene complex. Preparation of the nickel benzyl complex [BP3Ph]Ni(η2-Bn) allowed for exploration of addition–elimination chemistry for access to silylene complexes from simple primary and secondary silanes. Heating toluene solutions of [BP3Ph]Ni(η2-Bn) in the presence of CySiH3 resulted in the formation of a dimeric μ-silylene complex [Ni(μ-BP2Ph)(μ-SiHCy)]2. In the presence of 4-dimethylaminopyridine (DMAP), these conditions led to exclusive formation of the base-stabilized silylene com...