Methylene Reagents Research Articles

One-step conversion of dipicolinic acid to its dimethyl ester using monomethyl sulfate salts for GC-MS detection of bacterial endospores

Methyl sulfate (MeSO4-) salts were explored as thermochemolysis-methylation (TCM) reagents for gas chromatographic (GC) analysis of dipicolinic acid (DPA) as its dimethyl ester (Me2DPA) from bacterial endospores. The reaction was carried out under non-pyrolytic conditions by inserting a small coiled wire filament coated with the sample and reagents directly inside a GC injection port at 290 °C. Above 10 : 1 methyl donor/DPA ratios, alkali metal salts of MeSO4- effected 80-90% conversion of DPA to Me2DPA, which was 10-20 times more active than the same amount of tetramethylammonium hydroxide (TMA-OH) at this temperature. A quaternary salt mixture consisting of 1 : 3 : 1 : 3 TMA+/Na+/OH-/MeSO4- methylated spore DPA with an average conversion of 86% (mean conversion by TMA-OH under the same conditions was 4%). Therefore, the sensitivity for detection of bacterial endospores was increased over 20-fold compared to that observed with the more commonly employed TMA-OH methylating reagent. The limit of detection by this method was 9 × 104 total spores. Mechanisms describing the observed behavior are proposed and discussed. This is the first use of MeSO4- as a TCM reagent for GC.

Rhodium(I)-Catalyzed Direct Carboxylation of Arenes with CO2 via Chelation-Assisted C−H Bond Activation

Rh-catalyzed direct carboxylation of unactivated aryl C-H bond under atmospheric pressure of carbon dioxide was realized via chelation-assisted C-H activation for the first time. Variously substituted and functionalized 2-arylpyridines and 1-arylpyrazoles underwent the carboxylation in the presence of the rhodium catalyst and a stoichiometric methylating reagent, AlMe(2)(OMe), to give carboxylated products in good yields. The catalysis is proposed to consist of methylrhodium(I) species as the key intermediate, which undergoes C-H activation to afford rhodium(III), followed by reductive elimination of methane to give nucleophilic arylrhodium(I). This approach demonstrates promising application of C-H bond activation strategy in the field of carbon dioxide fixation.

Study of Michael addition on chalcones and or chalcone analogues

Michael addition reaction of 1,3-diphenyl-propenone 1a, e, and f with o-amino thiophenol in the presence of indium trichloride gave the benzothiazine derivatives 2a–c. Condensation of the compound 1a, e with o-phenylene diamine in triethylamine gave the benzodiazepine derivatives 3a–b. Cyclization of 1d with malononitrile in the presence of NaOR/EtOH gave the compound 4. Addition of thiobarbituric acid in triethylamin to 1a gave 5. Condensation of compound 1c with malononitrile in the presence ammonium acetate gave compound 6. 1,3-diphenyl-propenone 1a used as key starting chalcone to react with different active methylene reagents under phase-transfer catalysis condition gave compound 7–9. The structures of the prepared compounds were mainly confirmed on the basis of spectroscopic methods.

O-Methylation of the Phenolic Bio-oil with Dimethyl Carbonate in an Ionic Liquid [bmim]Cl

O-Methylation of phenols has been studied as an important organic reaction, and its products, aryl methyl ethers, are valuable intermediates in fine chemicals. The phenolic component is one of the factors leading to the thermal instability of biomass pyrolysis oils. O-Methylation of phenols is helpful to improve the stability of bio-oil. Using dimethyl carbonate (DMC) as a methylation reagent, model O-methylations of three phenols (phenol, guaiacol, and eugenol) have been investigated in an ionic liquid, 1-butyl-3-methylimidazolium chloride ([bmim]Cl), in the presence of water and carboxylic acid, separately. In [bmim]Cl at 130 °C, both hydrolysis of DMC and esterification of acetic acid with DMC would occur and compete with the O-methylation of phenol and decrease the yield of the methylation. However, the esterification of carboxylic acids is helpful for bio-oil upgrading. Under the same reaction conditions, the methylation was performed for a phenolic bio-oil, which is the ether extractive from the bot...

Synthesis of some new pyrazole and pyrazolopyrimidine derivatives

Abstract magnified image A series of pyrazolo [3,4‐d] pyrimidine, pyrazolo [1,5‐a] pyrimidine, and pyrazolyl triazoles have been prepared via reaction of ethyl 5‐amino‐3‐phenylpyrazole‐4‐carboxylate with isothiocyanic esters, α,β‐unsaturated nitriles, and some active methylene reagents. J. Heterocyclic Chem., (2010).

ChemInform Abstract: One-Pot Synthesis of Polyfunctionally Substituted 2,3-Dihydrothiazoles and Thiazolidinones.

The reaction of phenyl isothiocyanate with the active methylene reagents 1a–e gives the nonisolable 1:1 adducts 2a–e. The latter react with α-halogenated compounds, e.g. phenacyl bromide, bromoacetyl bromide, chloroacetone, chloroacetonitrile and some hydrazonoyl halides to give the corresponding polyfunctionally substituted 2,3-dihydrothiazoles or thiazolidinone ring systems.

ChemInform Abstract: Cinnamoylnitrile, Pyran, and Pyranopyrazole Derivatives Containing the Salicylanilide Moiety with Anticipated Molluscicidal Activity.

The reaction of new cinnamonitriles containing the salicylyl moiety with active methylene reagents leads to the formation of the corresponding heterocycles. Their reaction with aniline yields the corresponding salicylanilide derivatives. The obtained pyrans and anilides were tested for molluscicidal activity.

ChemInform Abstract: Synthesis and Palladium-Catalyzed Cycloaddition of the Bifunctional Conjunctive Reagent Methyl Z-1-Methyl-2-trimethylsilylmethyl-2-butenyl Carbonate.

A simple synthesis of (Z)-2-trimethylsilylmethyl-2-buten-1-ol from 2-butyn-1-ol provides ready access to disubstituted bifunctional conjunctive reagents such as the title compound. Palladium(0) catalysts initiate cycloaddition to electron-deficient olefins to form methylenecyclopentanes with excellent regioselectivity

Application of Secondary Amines in the Synthesis of Some New Spiro Heterocyclic Compounds

1-Anilinocycloalkanecarbonitriles 1a–c were prepared and reacted with active methylene reagents to give compounds 5a–c through 10a–c and reacted with different other reagents such as benzaldehyde, ethyl aminoacetate, ethyl mercaptoacetate, or hydrazine carbothioamide, which afforded the desired spiro heterocycles compounds 11a–c through 14a–c.

ChemInform Abstract: 1,3‐Benzodithiole‐1,1,3,3‐tetraoxide (BDT) as a Versatile Methylation Reagent in Catalytic Enantioselective Michael Addition Reaction with Enals.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis and antiproliferative activity of indolizinophthalazine-5,12-dione derivatives, DNA topoisomerase IB inhibitors

A series of novel indolizinophthalazine-5,12-dione derivatives were designed and synthesized by the reaction of 6,7-dichlorophthalazine-5,8-dione with active methylene reagents (AMR) and pyridine derivatives. Some of synthesized compounds exhibited significant in vitro antiproliferative activity at micromolar level toward four human tumor cell lines, including lung adenocarcinoma cell, large-cell lung carcinoma cell, breast carcinoma cell and ardriamycin-resistance breast carcinoma cell. The DNA topoisomerase IB inhibitory assay indicated that DNA topoisomerase IB might be a biological target of the synthesized compounds.

Synthesis, Crystal Structure, and Reactivity of the Strong Methylating Agent Me2B12Cl12

Synthesis, Crystal Structure, and Reactivity of the Strong Methylating Agent Me₂B₁₂Cl₁₂

A cellulose synthase-like protein is required for osmotic stress tolerance in Arabidopsis

Osmotic stress imposed by soil salinity and drought stress significantly affects plant growth and development, but osmotic stress sensing and tolerance mechanisms are not well understood. Forward genetic screens using a root-bending assay have previously identified salt overly sensitive (sos) mutants of Arabidopsis that fall into five loci, SOS1 to SOS5. These loci are required for the regulation of ion homeostasis or cell expansion under salt stress, but do not play a major role in plant tolerance to the osmotic stress component of soil salinity or drought. Here we report an additional sos mutant, sos6-1, which defines a locus essential for osmotic stress tolerance. sos6-1 plants are hypersensitive to salt stress and osmotic stress imposed by mannitol or polyethylene glycol in culture media or by water deficit in the soil. SOS6 encodes a cellulose synthase-like protein, AtCSLD5. Only modest differences in cell wall chemical composition could be detected, but we found that sos6-1 mutant plants accumulate high levels of reactive oxygen species (ROS) under osmotic stress and are hypersensitive to the oxidative stress reagent methyl viologen. The results suggest that SOS6/AtCSLD5 is not required for normal plant growth and development but has a critical role in osmotic stress tolerance and this function likely involves its regulation of ROS under stress.

Reaction of Cage-opened Fullerene Derivative with Grignard Reagents and Subsequent Transannular Cyclization

Abstract 1,2-Addition of methyl and allyl Grignard reagents to a cage-opened fullerene derivative 2a selectively proceeded at −20 °C in THF at one of the two carbonyl groups. Under acidic conditions, the resulting alcohol underwent a transannular cyclization. The elevated LUMO levels of these products were shown by electrochemical and theoretical investigations.

1,3-Benzodithiole-1,1,3,3-tetraoxide (BDT) as a versatile methylation reagent in catalytic enantioselective Michael addition reaction with enals

Abstract A protocol of an organocatalytic highly enantioselective conjugate addition of nucleophilic BDT to enals has been developed and the versatile Michael adducts serve as useful building blocks for a variety of organic transformations.

An Efficient Preparation of N-Methyl-α-amino Acids from N-Nosyl-α-amino Acid Phenacyl Esters

In this paper we describe a simple and efficient solution-phase synthesis of N-methyl-N-nosyl-alpha-amino acids and N-Fmoc-N-methyl-alpha-amino acids. This represents a very important application in peptide synthesis to obtain N-methylated peptides in both solution and solid phase. The developed methodology involves the use of N-nosyl-alpha-amino acids with the carboxyl function protected as a phenacyl ester and the methylating reagent diazomethane. An important aspect of this synthetic strategy is the possibility to selectively deprotect the carboxyl function or alternatively both amino and carboxyl moieties by using the same reagent with a different molar excess and under mild conditions. Furthermore, the adopted procedure keeps unchanged the acid-sensitive side chain protecting groups used in Fmoc-based synthetic strategies.

Design, Synthesis, and Cytotoxicity of Indolizinoquinoxaline-5,12-dione Derivatives, Novel DNA Topoisomerase IB Inhibitors

A series of new indolizinoquinoxaline-5,12-dione derivatives were designed and synthesized via a heterocyclization reaction of 6,7-dichloroquinoxaline-5,8-dione with active methylene reagents and pyridine derivatives. The synthesized compounds exhibited significant activity to inhibit the growth of four human tumour cell lines, including lung adenocarcinoma cell, large-cell lung carcinoma cell, breast carcinoma cell, and ardriamycin-resistant breast carcinoma cell at micromolar range. These compounds were also investigated for their inhibition to DNA topoisomerase IB activity. The results indicated that the indolizinoquinoxaline-5,12-dione structure might be a potential pharmacophore in anti-cancer drug design.

A nitric oxide/cysteine interaction mediates the activation of soluble guanylate cyclase

Nitric oxide (NO) regulates a number of essential physiological processes by activating soluble guanylate cyclase (sGC) to produce the second messenger cGMP. The mechanism of NO sensing was previously thought to result exclusively from NO binding to the sGC heme; however, recent studies indicate that heme-bound NO only partially activates sGC and additional NO is involved in the mechanism of maximal NO activation. Furthermore, thiol oxidation of sGC cysteines results in the loss of enzyme activity. Herein the role of cysteines in NO-stimulated sGC activity investigated. We find that the thiol modifying reagent methyl methanethiosulfonate specifically inhibits NO activation of sGC by blocking a non-heme site, which defines a role for sGC cysteine(s) in mediating NO binding. The nature of the NO/cysteine interaction was probed by examining the effects of redox active reagents on NO-stimulated activity. These results show that NO binding to, and dissociation from, the critical cysteine(s) does not involve a change in the thiol redox state. Evidence is provided for non-heme NO in the physiological activation of sGC in context of a primary cell culture of human umbilical vein endothelial cells. These findings have relevance to diseases involving the NO/cGMP signaling pathway.

Nickel N-Heterocyclic Carbene Catalyst for Cross-Coupling of Neopentyl Arenesulfonates with Methyl and Primary Alkyl Grignard Reagents

Nickel N-heterocyclic carbene (NHC) catalytic system prepared in situ by the reaction of Ni(acac)(2) with NHC precursor efficiently catalyzed the cross-coupling reaction of alkoxysulfonylarenes with methyl, neopentyl, and benzyl Grignard reagents at ambient temperature.

A novel synthesis of some 1,4‐phenylene‐bis‐heterocyclic carboxamide derivatives

Abstract magnified image N,N′‐(1,4‐phenylene)bis(3‐oxo‐3‐phenylpropanamide) 1 reacts with DMFDMA in refluxing toluene to afford N,N′‐(1,4‐phenylene)bis(2‐benzoyl‐3‐(dimethylamino)acrylamide) 2. Compound 2 reacts with a twofold excess of the active methylene reagents 3a, 3b, 3c to afford the pent‐2‐enediamide derivatives 7 and 8a, 8b, respectively. Compounds 7 and 8a could be cyclized to afford the same compound N,N′‐(1,4‐phenylene)bis(5‐cyano‐6‐oxo‐2‐phenyl‐1,6‐dihydropyridine‐3‐carboxamide) 9a while 8b was cyclized to afford the 6‐thioxo analogue 9b. Compound 2 reacts with hydrazine derivatives 10a, 10b in refluxing ethanol/piperidine to afford the hydrazinylacrylamide derivatives 11a, 11b, which have been cyclized to the corresponding N,N′‐(1,4‐phenylene)bis(1H‐pyrazole‐4‐carboxamide) derivatives 12a, 12b, respectively. Compound 2 reacts also with urea derivatives 13a, 13b, 13c in refluxing ethanol/piperidine to afford the N,N′‐(1,4‐phenylene)bis(2‐benzoyl‐3‐substituted‐acrylamide) derivatives 14a‐c, which could be cyclized into N,N′‐(1,4‐phenylene)bis(6‐phenyl‐1,2‐dihydropyrimidine‐5‐carboxamide)‐2‐oxo; 2‐thioxo or 2‐imino derivatives 15a, 15b, 15c, respectively. J. Heterocyclic Chem., (2009).