Methoxy Methyl Research Articles

A general and stereoselective approach to 14-membered cyclic bis-semicarbazones involving BF3-catalyzed amidoalkylation of 2-(trimethylsilyloxy)propene.

A general and stereoselective five-step approach to 14-membered cyclic bis-semicarbazones, 5,12-diaryl-7,14-dimethyl-1,2,4,8,9,11-hexaazacyclotetradeca-7,14-diene-3,10-diones, starting from aldehyde semicarbazones has been developed. The key intermediates, 4-(3-oxobut-1-yl)semicarbazones, were prepared by BF3-catalyzed amidoalkylation of 2-(trimethylsilyloxy)propene with 4-[(aryl)(methoxy)methyl]- or 4-[(aryl)(tosyl)methyl]semicarbazones. Treatment of these intermediates with excess of hydrazine gave hydrazones of 4-(3-oxobut-1-yl)semicarbazones or 4-(3-oxobut-1-yl)semicarbazides, which in the presence of TsOH were converted into the target macrocycles. All steps of this approach could be scaled up easily to the multi-gram level.

Effect of solvent type on the formation rate of benzyl cation intermediate in acidolysis of lignin

Abstract The purpose of this study was to examine how the type of solvent among aqueous 1,4-dioxane, tetrahydrofuran, ethanol, iso-propyl alcohol, or ethylene glycol and its content (mol%) affect the formation rate of benzyl cation intermediate (BC) in the acidolysis of lignin, using a simple model compound, 1,2-dimethoxy-4-methoxymethylbenzene. Because the BC forms from the model compound via two steps, i.e., protonation of the benzyl methoxymethyl group as the pre-equilibrium step and liberation of the methanol as the rate-determining step, the observed variation of the formation rate with type of solvent and solvent content originates from the effects on both steps undistinguishably. The formation rate of BC decreased with increasing mol% of any of the organic solvents for a range of relatively low mol%, but increased with it for relatively high mol%. The formation rate varied more in the ether than in the alcohol systems. These results seem to be regulated by the effect of changing the mol% on the pre-equilibrium step, i.e., on the proton activity, rather than on the rate-determining step. Two reaction products, 4-alkoxymethyl-1,2-dimethoxybenzene and 4-hydroxymethyl-1,2-dimethoxybenzene, exclusively formed in the aqueous alcohol systems. The former compound was confirmed to be thermodynamically more stable and kinetically the more favorable product.

Phosphazene base-catalyzed hydroamination of aminoalkenes for the construction of isoindoline scaffolds: Application to the total synthesis of aristocularine

A method for isoindoline synthesis via phosphazene base-catalyzed intramolecular hydroamination of aminoalkenes was developed. The reaction has a broad functional group tolerance, including for halide, cyano, and methoxy groups, and could also be used to synthesize tetrahydroisoquinoline, pyrrolidine, and piperidine. The method was used as a key step in the total synthesis of aristocularine in six steps in 35% overall yield. The strategy involved the construction of an isoindoline core through controlling the formation of the desired CN bond, with the relatively labile methoxymethyl group and arylbromide remaining intact.

Asymmetric synthesis of a cyclopropanecarboxylic acid derivative – the potential agonist/antagonist of GABA receptors

The synthesis of enantiomerically pure (1S,2S,S P)-1-[hydroxy(methyl)phosphonyl]-2-aminocyclopropanecarboxylic acid (1) (a potential agonist/antagonist of GABA receptors) was accomplished in six steps based on optically inactive methyl 2-[methoxy(methyl)phosphonyl]acrylate (2). The key steps of this synthesis included the cyclopropane ring formation by the asymmetric cyclopropanation reaction of 2 with (S)-dimethylsulfonium(p-tolylsulfinyl)methylide (3), regio and stereoselective installation of ethoxycarbonyl group in the cyclopropane ring, and the chemoselective desulfinylation reaction conducted with phenylsilane under the basic conditions.

Detailed DFT/MD simulation, surface analysis and electrochemical computer explorations of aldehyde derivatives for mild steel in 1.0 M HCl

Corrosion prevention in mild steel (MS) is a major issue in the industry. The development of an effective protection strategy is a popular research area. In this work, two molecules, namely methoxy cinnamaldehyde (MCA) and methyl cinnamaldehyde (MeCA) were evaluated as corrosion inhibitors for mild steel in 1.0 M HCl solution, providing a strong basis for the development of new inhibitors platform in the field of corrosion. The corrosion inhibition performance of MCA and MeCA has been studied by using weight loss, Impedance Spectroscopy (EIS), Potentiodynamic Polarization (PDP), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX) analysis, quantum chemical calculations and molecular dynamics (MD) simulation. Results showed that inhibition effectiveness of MCA and MeCA increases with their concentration. Polarization results showed that MCA and MeCA displayed mixed type behaviour. Inhibition efficiencies of MCA and MeCA followed the order: 88% (MCA) < 74% (MeCA). MeCA and MCA inhibit corrosion by adsorbing on MS surface and their adsorption mode followed Langmuir adsorption isotherm via physico-chemical adsorption. SEM/EDX observations of the electrode surface confirm the formation of a film on the metal surface. Theoretical calculations obtained from DFT and Molecular Dynamics (MD) simulation were used to investigate the correlation between the molecular structure of inhibitors and their corrosion inhibition performances, which agree well with the experimental results.

Design and Self-Assembling Behaviour of Calamitic Reactive Mesogens with Lateral Methyl and Methoxy Substituents and Vinyl Terminal Group.

Smart self-organising systems attract considerable attention in the scientific community. In order to control and stabilise the liquid crystalline behaviour, and hence the self-organisation, the polymerisation process can be effectively used. Mesogenic units incorporated into the backbones as functional side chains of weakly cross-linked macromolecules can become orientationally ordered. Several new calamitic reactive mesogens possessing the vinyl terminal group with varying flexible chain lengths and with/without lateral substitution by the methyl (methoxy) groups have been designed and studied. Depending on the molecular structure, namely, the type and position of the lateral substituents, the resulting materials form the nematic, the orthogonal SmA and the tilted SmC phases in a reasonably broad temperature range, and the structure of the mesophases was confirmed by X-ray diffraction experiments. The main objective of this work is to contribute to better understanding of the molecular structure–mesomorphic property relationship for new functional reactive mesogens, aiming at further design of smart self-assembling macromolecular materials for novel sensor systems.

Environmental modelling of hexamethoxymethylmelamine, its transformation products, and precursor compounds: An emerging family of contaminants from tire wear

Hexamethoxymethylmelamine (HMMM) is a polymer crosslinking agent used commercially to manufacture tires. HMMM is a ubiquitous contaminant in urban surface waters due to its presence in tire-wear particles and its tendency to be transported into receiving waters during rain events through road runoff. It has recently been determined that this chemical readily transforms into numerous other compounds, several of which have also been detected in the aquatic environment. However, there is limited knowledge about the fate and distribution of HMMM and its likely transformation products and precursor compounds. COSMO-RS solvation theory was used to estimate the physico-chemical properties of HMMM and 24 related derivatives, including their aqueous solubility, various partitioning properties, vapour pressure, and melting point. Using these properties as inputs to the Equilibrium Criterion (EQC) fugacity-based multimedia model, three different emission scenarios were modeled. Overall, these compounds were predicted to readily partition into aqueous media, with distributions in water increasing with the loss of methoxymethyl groups. In addition, the persistence of the transformation products of HMMM was predicted to decline with the extent of these transformations. The EQC model predictions indicate that these compounds are subject to overland transport into surface waters. This study provides insights into the fate and behaviour of HMMM and its transformation compounds and contributes to the growing literature on the hazards of organic chemicals derived from tire wear.

The Formation of C3O3H6 Structural Isomers in the Gas Phase through Barrierless Pathways: Formation and Spectroscopic Characterization of Methoxy Acetic Acid

Abstract Gas phase formation processes feasible at low temperatures are determined theoretically for 38 isomers obeying the C3O3H6 empirical formula, one of them, the simplest ketose dihydroxyacetone, has been observed in gas phase sources. A preliminary search for isomeric forms first targets ethoxy formic acid (C2H5–O–COOH) as the most stable isomer followed by lactic acid. Profiles corresponding to the minimum energy pathways reveal that the favored conformers of 14 of these isomers can be formed in the gas phase through 29 barrierless processes involving the OH*, CH3O*, HCO*, CH3*, CH2OH, HCOO*, and OHCO* radicals, all of them observed in the interstellar medium. Kinetic rates are provided at 200, 298, and 500 K, confirming the suitability of 16 processes at low temperatures. Faster processes involve the OH hydroxyl radical whereas, to a lesser degree, the processes involving the HOCO radical and the methoxy methyl radical CH3O*, are quite significant. Spectroscopic parameters (rovibrational and torsional) are obtained for methoxy acetic acid (CH3–O–CH2COOH) for which two low-lying isoenergetic conformers can be produced from the CH3OCH2* radical predicted to be a precursor of abundant observed molecules. Profiles and spectroscopic properties make methoxy acetic acid a good candidate to be detected in the gas phase of extraterrestrial sources.

Enantioselective Total Synthesis of (+)-Alstilobanine C, (+)-Undulifoline, and (-)-Alpneumine H.

We report herein the enantioselective total synthesis of three monoterpene indole alkaloids, namely, (+)-alstilobanine C, (+)-undulifoline, and (-)-alpneumine H. The key features of our synthesis include: a) introduction of chirality via enantioselective deprotonation of a prochiral 4-substituted cyclohexanone; b) use of methoxymethyl (MOM) ether as both a hydroxyl protective group and a latent oxonium species for the formation of bridged oxepane and c) domino double reductive cyclization to build both the indole and the piperidine ring at the end of the synthesis. The synthesis confirmed the absolute configuration of these natural products assigned based on the biogenetic hypothesis.

Enantioselective Total Synthesis of (+)‐Alstilobanine C, (+)‐Undulifoline, and (−)‐Alpneumine H

AbstractWe report herein the enantioselective total synthesis of three monoterpene indole alkaloids, namely, (+)‐alstilobanine C, (+)‐undulifoline, and (−)‐alpneumine H. The key features of our synthesis include: a) introduction of chirality via enantioselective deprotonation of a prochiral 4‐substituted cyclohexanone; b) use of methoxymethyl (MOM) ether as both a hydroxyl protective group and a latent oxonium species for the formation of bridged oxepane and c) domino double reductive cyclization to build both the indole and the piperidine ring at the end of the synthesis. The synthesis confirmed the absolute configuration of these natural products assigned based on the biogenetic hypothesis.

A Convenient Protecting Group for Uridine Ureido Nitrogen: (4,4'-Bisfluorophenyl)methoxymethyl group.

(4,4'-Bisfluorophenyl)methoxymethyl (BFPM) group of uridine ureido nitrogen shows good relative stability in a variety of chemical transformation reactions for uridine. The BFPM group can be cleaved via 2% of TFA in CH2Cl2 without affecting the Boc group.

A new C-anionic tripodal ligand 2-{bis(benzothiazolyl)(methoxy)methyl}phenyl and its bismuth complexes.

A new tripodal C-anionic ligand, 2-{bis(benzothiazolyl)(methoxy)methyl}phenyl (L), was stably generated by the reaction of the ligand precursor (L'), the corresponding bromide (2-BrC6H4)(MeO)C(C7H4NS)2 (C7H4NS = 2-benzothiazolyl), with nBuLi at -104 °C in the presence of TMEDA (N,N,N',N'-tetramethylethylenediamine). The ligand lithium salt reacted with BiCl3 to give a 2 : 1 complex L2BiCl. A 1 : 1 complex LBiCl2 was obtained in good yield by the redistribution reaction between L2BiCl and BiCl3. X-ray diffraction analysis revealed that the ligand L coordinated in an expected κ3-C,N,N' coordination mode in LBiCl2, while it coordinated in κ3-C,N,O and κ2-C,O coordination modes in L2BiCl. The ligand precursor reacted with BiX3 (X = Cl, Br) to give 1 : 1 complexes L'BiX3 and was found to act as a neutral tripodal C(π),N,N-ligand.

Efficient synthesis of α-amino secondary amides by direct aminocarbonylation of N-Boc-imines using carbamoylsilane as an amide source

A novel and practical procedure for the preparation of α-amino secondary amides by the aminocarbonylation of N-Boc-imines using carbamoylsilanes bearing methoxymethyl group as secondary amides source is presented herein. The protocol tolerates N-Boc-imines bearing different groups, including aryl, double bond conjugated aryl, heteroaryl and aliphatic groups. The reactions provide good to excellent yields of the products under mild and catalysts-free conditions. The electronic property and the steric hindrance of substituent on the N-Boc-imines affect the reaction.

Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome

Sarecycline is a new narrow-spectrum tetracycline-class antibiotic approved for the treatment of acne vulgaris. Tetracyclines share a common four-ring naphthacene core and inhibit protein synthesis by interacting with the 70S bacterial ribosome. Sarecycline is distinguished chemically from other tetracyclines because it has a 7-[[methoxy(methyl)amino]methyl] group attached at the C7 position of ring D. To investigate the functional role of this C7 moiety, we determined the X-ray crystal structure of sarecycline bound to the Thermus thermophilus 70S ribosome. Our 2.8-Å resolution structure revealed that sarecycline binds at the canonical tetracycline binding site located in the decoding center of the small ribosomal subunit. Importantly, unlike other tetracyclines, the unique C7 extension of sarecycline extends into the messenger RNA (mRNA) channel to form a direct interaction with the A-site codon to possibly interfere with mRNA movement through the channel and/or disrupt A-site codon-anticodon interaction. Based on our biochemical studies, sarecycline appears to be a more potent initiation inhibitor compared to other tetracyclines, possibly due to drug interactions with the mRNA, thereby blocking accommodation of the first aminoacyl transfer RNA (tRNA) into the A site. Overall, our structural and biochemical findings rationalize the role of the unique C7 moiety of sarecycline in antibiotic action.

Synthesis and characterization of ricinoleic acid based hyperbranched alkyds for coating application

Hyperbranched alkyds based on ditrimethylolpropane, dimethylolpropionic acid, and ricinoleic acid were synthesized. The synthesized resins were characterized by the determination of hydroxyl and acid numbers, viscosity, average molecular masses, and molecular masses distribution. Compared with conventional alkyd resins of similar molar masses, the synthesized hyperbranched alkyds have significantly lower viscosity values at a given temperature. Therefore, a significantly smaller amount of organic solvents is required for their dissolution and can be used as precursors to obtain eco-friendly coatings. The obtained hyperbranched alkyd resins were cured by two commercial melamine resins (mass ratio 70:30). The curing of the resin mixtures was examined by FTIR spectroscopy, rheometry, and by the determination of gel content. The curing of the resin mixtures proceeds via the reactions between hydroxyl and carboxyl groups of hyperbranched alkyds with isobutoxymethyl and methoxymethyl groups in melamine resins. Hyperbranched alkyd/melamine resin mixtures were cured at 150 °C for 60 min. Thermal properties, dynamic mechanical behavior, physico-mechanical characteristics, and chemical resistance of cured films were determined. The crosslinking densities of films obtained from mixtures using hexamethoxymethyl melamine resin are significantly higher than those based on mixtures using isobutylated melamine resin. The thermal degradation of cured films is a complex process, and their thermal stability increases slightly with the increase of hyperbranched alkyds generation. It is assumed that mixtures of synthesized hyperbranched alkyds with melamine resins would be suitable for obtaining the coatings with good chemical resistance and physical-mechanical properties.

Synthesis and Structure of Tin and Germanium Complexes as Precursors Containing Alkoxyaminoalkoxide Ligands for Thin Film Transistors

This paper describes the preparation of four novel Sn and Ge complexes containing alkoxyaminoalkoxide type ligands {L1H = 1‐[methoxy(methyl)amino]‐2‐methylpropan‐2‐ol; L2H = 1‐[methoxy(methyl)amino]‐2‐methylbutan‐2‐ol} for potential use as precursors for thin film transistors. All compounds were prepared at room temperature by stirring a solution containing Sn(btsa)2 [btsa = bis(trimethylsilyl)amide] or Ge(btsa)2 with two equivalents of L1H or L2H to form Sn(L1)2 (1), Sn(L2)2 (2), Ge(L1)2 (3) and Ge(L2)2 (4). All of the complexes were characterized by NMR and FTIR spectroscopy as well as elemental and thermogravimetric analyses. When the more symmetric and compact ligand L1H was applied, solid products 1 and 3 were generated and their structures were studied using X‐ray diffraction. Applying the strategy of ligand design at the molecular level, the symmetric ligand was changed to an asymmetric one, replacing one of the two neighboring methyl groups of the amino alcohol group with an ethyl group, and forming liquid complexes 2 and 4 for both metals.

Anchimerically Assisted Selective Cleavage of Acid-Labile Aryl Alkyl Ethers by Aluminum Triiodide and N,N-Dimethylformamide Dimethyl Acetal.

Aluminum triiodide is harnessed by N,N-dimethylformamide dimethyl acetal (DMF-DMA) for the selective cleavage of ethers via neighboring group participation. Various acid-labile functional groups, including carboxylate, allyl, tert-butyldimethylsilyl (TBS), and tert-butoxycarbonyl (Boc), suffer the conditions intact. The method offers an efficient approach to cleaving catechol monoalkyl ethers and to uncovering phenols from acetal-type protecting groups such as methoxymethyl (MOM), methoxyethoxymethyl (MEM), and tetrahydropyranyl (THP) chemoselectively.

Synthesis of the pentasaccharide repeating unit of the O-antigen from Enterobacter cloacae C4115 containing the rare α-d-FucNAc.

Total synthesis of the pentasaccharide repeating unit associated with the O-antigen of Enterobacter cloacae C4115 is reported. The synthesis of the said oligosaccharide was accomplished through rational protecting group manipulations on commercially available monosaccharides followed by stereoselective glycosylations either by activation of thioglycosides or glycosyl trichloroacetimidates and was found to be productive. Towards the synthesis of the rare sugar unit, α-d-FucNAc in this case, it was established that the methoxymethyl (MOM) group is advantageous over the earlier reported tetrahydro pyran (THP) protection. The effect of MOM-protection was successfully tested for the synthesis of a rare sugar synthon which can serve as a precursor to the rare d-fucosamine residue.

Identification of novel dynamin-related protein 1 (Drp1) GTPase inhibitors: Therapeutic potential of Drpitor1 and Drpitor1a in cancer and cardiac ischemia-reperfusion injury.

Mitochondrial fission is important in physiological processes, including coordination of mitochondrial and nuclear division during mitosis, and pathologic processes, such as the production of reactive oxygen species (ROS) during cardiac ischemia-reperfusion injury (IR). Mitochondrial fission is mainly mediated by dynamin-related protein 1 (Drp1), a large GTPase. The GTPase activity of Drp1 is essential for its fissogenic activity. Therefore, we aimed to identify Drp1 inhibitors and evaluate their anti-neoplastic and cardioprotective properties in five cancer cell lines (A549, SK-MES-1, SK-LU-1, SW 900, and MCF7) and an experimental cardiac IR injury model. Virtual screening of a chemical library revealed 17 compounds with high predicted affinity to the GTPase domain of Drp1. In silico screening identified an ellipticine compound, Drpitor1, as a putative, potent Drp1 inhibitor. We also synthesized a congener of Drpitor1 to remove the methoxymethyl group and reduce hydrolytic lability (Drpitor1a). Drpitor1 and Drpitor1a inhibited the GTPase activity of Drp1 without inhibiting the GTPase of dynamin 1. Drpitor1 and Drpitor1a have greater potency than the current standard Drp1 GTPase inhibitor, mdivi-1, (IC50 for mitochondrial fragmentation are 0.09, 0.06, and 10μM, respectively). Both Drpitors reduced proliferation and induced apoptosis in cancer cells. Drpitor1a suppressed lung cancer tumor growth in a mouse xenograft model. Drpitor1aalso inhibited mitochondrial ROS production, prevented mitochondrial fission, and improved right ventricular diastolic dysfunction during IR injury. In conclusion, Drpitors are useful tools for understanding mitochondrial dynamics and have therapeutic potential in treating cancer and cardiac IR injury.

Charge-Discharge Characteristics on Low Viscosity Phosphonium Ionic Liquid Electrolytes for Lithium Ion Battery

We evaluated low viscosity Ionic Liquids (ILs) based on quaternary phosphonium cations as electrolytes for Lithium Ion secondary Battery (LIB) in this work. The secondary batteries are required more safety and higher energy density per volume and/or mass for electric vehicles (EVs) to equipped to convenient driving technology, i.e. IOT, electric sensing technology and devices. LIB is one of the promising batteries for EVs, and is mainly used for cellular phones and portable devices for its large capacity and light weight. Carbonate solvents are commercially used as an electrolyte in LIBs, but they are highly inflammable for a short circuit and/or thermal runaway. Hence we focused on ILs as an electrolyte for LIB because of their properties (e.g. incombustibility, hard volatility, wide potential window and high ion conductivity, etc.). Since the discovery of water stable 1-ethyl-3-methylimidazolium tetrafluoroborate 1), ILs have attracted attention. The ILs which are based on mainly imidazolium cations, pyridinium cations and quaternary ammonium cations, etc., have been studied in various fields including electrolytes for LIB 2, 3). On the other hand, ILs based on quaternary phosphonium cations have more unique properties, especially, i.e. lower viscosity than quaternary ammonium cations system 4), while a few electrochemical properties as electrolyte for LIB are reported 5, 6). Moreover, they have higher thermal stability and wider potential window than ammonium cation systems, so their properties are advantageous for safety. High discharge capacities of near the theoretical capacity of LiCoO2 and coulomb efficiencies of ca. 100% were obtained during Charge-discharge cycle tests on P111X-FSA system which consist of trimethylphoshine (TMP) based phosphonium cations (P111X + ; X = 1O1(methoxymethyl group), Al(allyl group) etc.) and bis(fluorosulfonyl)amide anion (FSA-). Moreover, the discharge rate capability of P111(1O1)-FSA was quite higher than another functionalized ILs, while the ion conductivity was not so higher. This is indicated that some physical parameters, e.g. transport numbers of Li+ in ILs or electrode-electrolyte interfacial phenomenon would affect to the rate characteristics. [References] 1) S. Wilkes, and M.J. Zaworotko, J. Chem. Soc. Chem. Commun., 0, 965-967 (1992). 2) N. Papageourgiou, Y. Athanassov, M. Armand, P. Bonhote, H. Pettersson, A. Azam, and M. Gratzel, J. Electrochem. Soc., 143(10), 3099-3108 (1996). 3) H. Sakaibe, H. Matsumoto, and K. Tatsumi, J. Power Sources, 146, 693-697 (2005). 4) K. Tsunashima, F. Yonekawa, and M. Sugiya, Electrochem. Solid-State Lett., 12(3), A54-57 (2009). 5) K. Tsunashima, Y. Sakai, and M Matsumiya, Electrochem. Commun., 39, 30-33 (2014). 6) X. Lin, R. Kavian, Y. Lu, Q. Hu, Y. Shao-Horn, and M. W. Grinstaff, Chem. Sci., 6, 6601-6606 (2015).