Sodium Methoxide In Methanol Research Articles

A novel synthesis of β- d-mannopyranosyl azide by phase transfer catalysis

A simple stereoselective synthesis of per- O-benzoyl-β- d-mannopyranosyl azide from per- O-benzoyl-α- d-mannopyranosyl bromide using phase transfer catalysis was developed. The stereochemistry at C-1 of the anomeric O-benzoylated α- and β- d-mannopyranosyl azides was unambiguously established using 2D NOESY NMR spectroscopy. Pure deprotected β- d-mannopyranosyl azide was prepared by debenzoylation with sodium methoxide in methanol.

Synthesis of Functionalized Dialkyl Cyclobutane-1,1-dicarboxylates and Alkyl 5,6-Dihydro-4H-pyran-3-carboxylates via Michael-Induced Ring Closure of δ-Chloro-α,β-Unsaturated Diesters and Ketoesters

Michael-induced ring closure (MIRC) of dimethyl 2-(3-chloro-2,2-dimethylpropylidene)malonate, upon treatment with sodium tert-butylthiolate, sodium methoxide or sodium cyanide in methanol, provided a short and efficient synthesis of new 2-functionalized cyclobutane-1,1-dicarboxylic esters. Under similar conditions, methyl 2-acetyl-5-chloro-4,4-dimethylpent-2-enoate afforded 4-functionalized methyl 5,6-dihydro-4H-pyran-3-carboxylates as the MIRC products.

Biodiesel Production via Rapid Transesterification

Biodiesel, an alternative diesel fuel derived from vegetable oil, animal fats, or waste vegetable oils, is obtained by reacting the oil or fat with monohydric aliphatic alcohols having 1–5 carbon atoms (ester exchange or transesterification) to their esters. Chemically, biodiesel is a fatty acid (m)ethyl ester. Biodiesel plays an important role in meeting future fuel requirements in view of its ability to reduce emissions from diesel engines for many air pollutant precursors, the lower toxicity of the diesel particulate matter emissions, and its edge over conventional diesel as they are obtained from renewable sources. In the supercritical alcohol transesterification method, the yield of conversion raises 50–95% for the first 8 min. In the catalytic supercritical methanol transesterification method, the yield of conversion raises 60–90% for the first minute. The reaction between sodium methoxide in methanol and a vegetable oil is very rapid; for example, they are completely transesterified in 4–6 min at room temperature.

Synthesis of 2‐imino‐7‐methyl‐2,3‐dihydroimidazo[1,2‐a]‐pyrimidin‐5(1H)‐ones and their reactions with nucleophiles

Abstractmagnified image[2‐Alkylthio‐6‐methyl‐4‐oxopyrimidin‐3(4H)‐yl]acetonitriles (3‐5) treated with sodium methoxide in methanol followed by ammonium chloride were cyclized to 2‐imino‐7‐methyl‐2,3‐dihydroimidazo[1,2‐a]‐pyrimidin‐5(1H)‐ones (6‐8). Under acid or base‐catalyzed hydrolysis they were converted to 7‐methyl‐imidazo[1,2‐a]pyrimidine‐2,5‐[1H,3H]‐diones (9‐11), whereas in the reaction with butyl‐ or benzylamine the corresponding 7‐methyl‐2‐(substitutedamino)imidazo[1,2‐a]pyrimidin‐5(3H)‐ones (13‐18) were produced. The latter were found to exist in two tautomeric forms in CDCl3 solution.

The Competition of the Loss of a Beta Fluoride and Hydron Transfer Between Carbon and Oxygen During Exchange and Elimination Reactions

Abstract Reactions of methanolic sodium methoxide with the series p-CF3C6H4C i HClRX [RX is -CH2Cl, -CH2F, -CHClF, -CHF2, -CF2Cl or -CF3] are reported to probe reaction mechanisms for dehydrohalogenation reactions compared to hydron exchange. All of the dehydrochlorinations and dehydrofluorinations from CH2F occur by a two step mechanism via a hydrogen-bonded carbanion intermediate. Dehydrofluorinations from CHF2 occurs via a carbanion no longer stabilized by a hydrogen bond and the fluoride ion is eliminated faster than proton transfer from methanol. Reactions from the CF3 occur from a similar intermediate but exchange of the benzylic proton is faster than the dehydrofluorination. Reactions of ethanolic sodium ethoxide are also reported with the series p-CF3C6H4C i HFRX [RX is -CH2F, -CHF2, -CF2Cl or -CF3]. Density functional calculations using B3LYP/6-31+G(d,p) were used to probe the compounds and intermediates.

Synthesis of Novel 3-Oxopiperidin-2-ones from Methyl 2-Alkoxy-5-amino-2-pentenoates

Alkylamino-substituted 2-alkoxy-2-pentenoates, obtained through ring transformation of 4-(1-chloro-1-methylethyl)-or 4-(2-halo-1,1-dimethylethyl)azetidin-2-ones upon treatment with sodium methoxide in methanol, have been evaluated as substrates for the cyclization towards pyrrolidines and piperidines. Thus, a convenient approach for the transformation of methyl 2-alkoxy-5-amino-4,4-dimethyl-2-pentenoates into 5,5-dimethyl-3-oxopiperidin-2-ones is described utilizing an excess of concentrated sulfuric acid.

Chemical analysis of atherosclerotic plaque cholesterol combined with histology of the same tissue

Sensitive method for chemical analysis of free cholesterol (FC) and cholesterol esters (CE) was developed. Mouse arteries were dissected and placed in chloroform-methanol without tissue grinding. Extracts underwent hydrolysis of cholesteryl esters and derivatization of cholesterol followed by liquid chromatography/mass spectrometry (LC/MS/MS) analysis. We demonstrated that FC and CE could be quantitatively extracted without tissue grinding and that lipid extraction simultaneously worked for tissue fixation. Delipidated tissues can be embedded in paraffin, sectioned, and stained. Microscopic images obtained from delipidated arteries have not revealed any structural alterations. Delipidation was associated with excellent antigen preservation compatible with traditional immunohistochemical procedures. In ApoE(-/-) mice, LC/MS/MS revealed early antiatherosclerotic effects of dual PPARalpha,gamma agonist LY465606 in brachiocephalic arteries of mice treated for 4 weeks and in ligated carotid arteries of animals treated for 2 weeks. Reduction in CE and FC accumulation in atherosclerotic lesions was associated with the reduction of lesion size. Thus, a combination of LC/MS/MS measurements of CE and FC followed by histology and immunohistochemistry of the same tissue provides novel methodology for sensitive and comprehensive analysis of experimental atherosclerotic lesions.

Practical Methylation Procedure for (1H)‐1,2,4‐Triazole

Conversion of (1H)‐1,2,4‐triazole to its sodium salt with methanolic sodium methoxide is followed by reaction with iodomethane. A scalable approach that overcomes problems associated with water‐soluble starting material and water‐soluble product combined continuous extraction (chloroform/water) with a final short‐path distillation under a controlled vacuum to obtain spectroscopically pure 1‐methyl‐1,2,4‐triazole in 63% yield. Adaptation to microwave synthesis conditions, while providing a faster reaction time, offers no product yield or purification advantages over the conventional approach described. Conversions of this product to related derivatives such as 1,4‐dimethyl‐1,2,4‐triazolium iodide and 1‐methyl‐1,2,4‐triazolium hydrochloride are readily achieved.

Synthesis of Carbohydrate-Conjugated dT Analogues Using ‘Click Chemistry’

A new type furo[2,3-d]pyrimidine nucleoside conjugated with various carbohydrates was synthesized using Sonogashira coupling and ‘click chemistry’. In the subsequent deprotection of the 4-toluoyl and acetyl groups with catalytic sodium methoxide in methanol, the furo[2,3-d]pyrimidine rearranged to an opened ketone-type structure. Their structures were confirmed on the basis of spectroscopy.

Synthesis of Methyl 2-Amino-3H-1-benzazepine-4-carboxylates and 2-(Cyanomethyl)-2,3-dihydro-1H-indole-2-carboxylates from Morita-Baylis-Hillman Acetates of 2-(Acylamino)benzaldehydes

Methyl 2-Amino-3H-1-benzazepine-4-carboxylates or methyl 2-(cyanomethyl)-2,3-dihydro-1H-indole-2-carboxylates were prepared from the reaction of 3-[2-formamido-, 2-acetamido-, or 2-(propanoylamino)phenyl]-substituted methyl 2-(cyanomethyl)propenoates with sodium methoxide in methanol, respectively. The latter were readily obtained from the Morita-Baylis-Hillman reaction of N-protected 2-aminobenzaldehydes with methyl acrylate followed by acetylation and cyanation.

Ring transformations of heterocyclic compounds. XXV. Phenanthrene aldehyde imines via ring transformation of pyrylium salts with methylenedihydroisoquinolines—A novel access to the phenanthrene skeleton

Abstractmagnified imageThe ring transformation of 2,4,6‐triarylpyrylium salts 1 with 2‐methylenedihydroisoquinolines 6, generated in situ from the related 2‐methylisoquinolinium salts 2, in the presence of bases is reported. Whereas the transformation of 1 with 2(6) and sodium methoxide in methanol leads to 2‐(2,4,6‐triarylphenyl)isoquinolinium salts, with sodium ethoxide in ethanol the aryl substituted phenanthrene‐9‐carbaldehyde imines 4 are obtained, the structure of which was confirmed by an X‐ray structure determination of the 1‐(4‐methylphenyl) substituted derivative. Acid catalyzed hydrolysis of the imines 4 gives rise to the parent phenanthrene aldehydes. The transformation 1 + 2(6) → 4 represents a novel access to the phenanthrene skeleton.

Novel Gold(I) 7-Azacoumarin Complex: Synthesis, Structure, Optical Properties, and Cytotoxic Effects

A mixture of pyridoxalrhodanine, triethylphosphinegold(I) chloride, and sodium methoxide in methanol unexpectedly afforded the azacoumarin complex [Au(TS)(PEt3)] [HTS = 5-(hydroxymethyl)-8-methyl-3-thiol-7-azacoumarin], which was characterized by X-ray diffractometry. Its crystals consist of independent molecules in which the metal atom is bound to the azacoumarin [Au-S = 2.9458(18) A] and the phosphine [Au-P = 2.262(2) A] in an almost linear arrangement [P1-Au1-S1 = 176.93(7) degrees]. The complex showed better in vitro antitumor activity than cisplatin against the cisplatin-resistant cell line A2780cis.

Novel synthesis of 2-aminopentanedinitriles from 2-(bromomethyl)aziridines and their transformation into 2-imino-5-methoxypyrrolidines and 5-methoxypyrrolidin-2-ones

1-Arylmethyl-2-(bromomethyl)aziridines were transformed into 2-[ N-(arylmethyl)amino]pentanedinitriles upon treatment with an excess of potassium cyanide in DMSO through an unprecedented and peculiar reaction mechanism, involving base-induced ring opening of intermediate 2-(cyanomethyl)aziridines into allylamines, followed by migration of the double bond out of the conjugation towards aldimines via enamine intermediates. The resulting aminopentanedinitriles served as substrates for the synthesis of novel 2-imino-5-methoxypyrrolidines upon treatment with sodium methoxide in methanol, which were either acetylated at the free imino group to afford the more stable N-acetylimino derivatives or hydrolyzed towards the corresponding synthetically relevant 5-methoxypyrrolidin-2-ones.

Electroorganic synthesis of benzathine

Benzathine is prepared in good yields from cyanobenzene by a combination of electrochemical hydrogenation and Kolbe electrolysis using nickel and platinum electrodes in the presence of methanolic sodium methoxide in an undivided cell.

Domino Metal‐Free Allene‐β‐lactam‐Based Access to Functionalized Pyrroles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Caveolar Endocytosis and Microdomain Association of a Glycosphingolipid Analog Is Dependent on Its Sphingosine Stereochemistry

We have previously shown that glycosphingolipid analogs are internalized primarily via caveolae in various cell types. This selective internalization was not dependent on particular carbohydrate headgroups or sphingosine chain length. Here, we examine the role of sphingosine structure in the endocytosis of BODIPYtrade mark-tagged lactosylceramide (LacCer) analogs via caveolae. We found that whereas the LacCer analog with the natural (D-erythro) sphingosine stereochemistry is internalized mainly via caveolae, the non-natural (L-threo) LacCer analog is taken up via clathrin-, RhoA-, and Cdc42-dependent mechanisms and largely excluded from uptake via caveolae. Unlike the D-erythro-LacCer analog, the L-threo analog did not cluster in membrane microdomains when added at higher concentrations (5-20 microm). In vitro studies using small unilamellar vesicles and giant unilamellar vesicles demonstrated that L-threo-LacCer did not undergo a concentration-dependent excimer shift in fluorescence emission such as that seen with BODIPYtrade mark-sphingolipids with natural stereochemistry. Molecular modeling studies suggest that in d-erythro-LacCer, the disaccharide moiety extends above and in the same plane as the sphingosine hydrocarbon chain, while in L-threo-LacCer the carbohydrate group is nearly perpendicular to the hydrocarbon chain. Together, these results suggest that the altered stereochemistry of the sphingosine group in L-threo-LacCer results in a perturbed structure, which is unable to pack closely with natural membrane lipids, leading to a reduced inclusion in plasma membrane microdomains and decreased uptake by caveolar endocytosis. These findings demonstrate the importance of the sphingolipid stereochemistry in the formation of membrane microdomains.

Synthesis of β‐Fluoroalkyl‐β,β‐dimethoxy Ketones and β‐Fluoroalkyl‐β‐methoxy‐α,β‐enones.

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Synthesis and Characterization of Osmium(II) Trispyrazolylborate Complexes

Treatment of H2OsBr6 with excess 1,5-cyclooctadiene (cod) in boiling tert-butyl alcohol affords the polymer [OsBr2(cod)]x (1), which reacts with acetonitrile to form the mononuclear adduct OsBr2(cod)(CH3CN)2 (2). Polymer 1 reacts with potassium trispyrazolylborate (KTp) in ethanol to afford the hydride TpOs(cod)H (3) and the bromide complex TpOs(cod)Br (4). Bromide complex 4 reacts with sodium methoxide in methanol to afford TpOs(cod)OMe (5), which has been structurally characterized. Treatment of hydride 3 with methyl trifluoromethanesulfonate (MeOTf) in diethyl ether results in loss of methane and formation of the triflate complex TpOs(cod)OTf (6), which reacts with MgMe2 to give the methyl complex TpOs(cod)Me (7). The addition of bis(dimethylphosphino)methane (dmpm) to the known compound TpOs(PPh3)2Cl yields a mixture of the substitution products TpOs(eta1-dmpm)(PPh3)Cl (8) and TpOs(eta2-dmpm)Cl (9); the latter reacts with methyllithium to generate the methyl compound TpOs(dmpm)Me (10). NMR and IR data for these new compounds are reported. Crystal data for 5.MeOH at -80 degrees C are as follows: monoclinic, P2(1)/n, a = 10.728(1) A, b = 14.004(2) A, c = 13.906(2) A, beta = 102.42(6) degrees , V = 2040.3(5) A3, Z = 4, R(F) = 0.0247 for I > or = 2sigma(I), and R(wF2) = 0.0539 for all data.

Synthesis of 1-Arylmethyl-2-(cyanomethyl)aziridines and Their Ring Transformation into MethylN-(2-Cyanocyclopropyl)benzimidates

1-Arylmethyl-2-(cyanomethyl)aziridines were prepared in high yields from the corresponding 2-(bromomethyl)aziridines upon treatment with potassium cyanide in DMSO. Ring opening of the aziridine moiety with N-chlorosuccinimide in CCl4 and subsequent treatment of the thus formed 4-chloro-3-(N-chloro-N-(alpha,alpha-dichlorobenzyl)amino)butanenitriles with sodium methoxide in methanol resulted in novel methyl N-(2-chloro-1-(cyanomethyl)ethyl)benzimidates, although in low yields. The latter gamma-chloro nitriles were smoothly converted into methyl N-(2-cyanocyclopropyl)benzimidates as precursors of biologically relevant beta-ACC derivatives through a 1,3-cyclization protocol by reaction with potassium tert-butoxide in THF.

Comparison of gas‐phase acidities of some carbon acids with their rates of hydron exchange in methanolic methoxide

AbstractHydron exchange reaction rates, kexch M−1s−1, using methanolic sodium methoxide are compared with gas‐phase acidities, ΔG kcal/mol, for four 9‐YPhenylfluorenes‐9‐iH, seven YC6H4CiH(CF3)2, seven YC6H4CiHClCF3, and C6F5iH. Fourteen of the fluorinated benzylic compounds and pentafluorobenzene result in near unity experimental hydrogen isotope effects that suggest substantial amounts of internal return associated with the exchange process. Although the reactions of 9‐phenylfluorene have experimental isotope effects that appear to be normal in value, they do not obey the Swain–Schaad relationship. This suggests that they occur with small amounts of internal return. The entropies of activation, ΔS‡, are +12 to +14 eu, for the benzylic compounds and different significantly from those for the 9‐YPhenylfluorenes, ΔS‡ of −8 to −12 eu. The ΔS‡ ∼ 1 eu for the reactions of pentafluorobenzene falls between the other compounds. Density functional calculations using B3LYP/6‐31+G(d,p) are reported for the reactions of CH3O−(HOCH3)3 with C6F5H, C6H5CH(CF3)2, C6H5CHClCF3, and 9‐phenylfluorene. Copyright © 2006 John Wiley & Sons, Ltd.