NaOMe In MeOH Research Articles

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids.

(R,R)-Dimethyl tartrate acetonide 7 in THF/HMPA undergoes deprotonation with LDA and reaction at −78 °C during 12–72 h with a range of alkyl halides, including non-activated substrates, to give single diastereomers (at the acetonide) of monoalkylated tartrates 17, 24, 33a–f, 38a,b, 41 of R,R-configuration, i.e., a stereoretentive process (13–78% yields). Separable trans-dialkylated tartrates 34a–f can be co-produced in small amounts (9–14%) under these conditions, and likely arise from the achiral dienolate 36 of tartrate 7. Enolate oxidation and acetonide removal from γ-silyloxyalkyl iodide-derived alkylated tartrates 17 and 24 give ketones 21 and 26 and then Bamford–Stevens-derived diazoesters 23 and 27, respectively. Only triethylsilyl-protected diazoester 27 proved viable to deliver a diazoketone 28. The latter underwent stereoselective carbonyl ylide formation–cycloaddition with methyl glyoxylate and acid-catalysed rearrangement of the resulting cycloadduct 29, to give the 3,4,5-tricarboxylate-2,8-dioxabicyclo[3.2.1]octane core 31 of squalestatins/zaragozic acids. Furthermore, monoalkylated tartrates 33a,d,f, and 38a on reaction with NaOMe in MeOH at reflux favour (≈75:25) the cis-diester epimers epi-33a,d,f and epi-38a (54–67% isolated yields), possessing the R,S-configuration found in several monoalkylated tartaric acid motif-containing natural products.

A novel one-pot three-component approach to 4-amino-functionalized spiropyrimidine-2-thiones

A series of 4-amino-functionalized spiropyrimidine-2-thione derivatives were simply produced by the one-pot three-component reaction of alicyclic carbonyl compounds, nitriles containing an acidic methylene, and thiourea in the presence of NaOMe in MeOH.

Synthesis and biological evaluation of novel C1-glycosyl thiazole derivatives as acetylcholinesterase inhibitors

A new series of C1-glycosyl thiazole derivatives was synthesised by the reaction of 1-(1,3,4,6-tetra- O-acetyl-2-deoxy-β-D-glucopyranos-2-yl)thiourea with 2-bromoacetophenone derivatives. Subsequent removal of the acetyl groups were conducted using NaOMe–MeOH. The structures of all new products were confirmed by IR, 1H NMR and HRMS (ESI). The acetylcholinesterase inhibitory activities of these new compounds were tested. Among them, N-(2-acetamido-3,4,6-tri- O-acetyl-2-deoxy-β-D-glucopyranosyl)-4-(4-nitrophenyl)-1,3-thiazole-2-amine showed the best activity with an inhibition rate of 43.21%.

Experimental Study on the Reaction Pathway of α-Haloacetophenones with NaOMe: Examination of Bifurcation Mechanism

Abstract The reaction of PhCOCH2Br and NaOMe in MeOH gave PhCOCH2OH as the major product and PhCOCH2OMe as the minor product. Substituent effects on the reactivity and product selectivity revealed that an electron-withdrawing substituent on the phenyl ring enhanced the overall reactivity and gave more alcohol than ether. It was indicated that the alcohol was formed via carbonyl addition-epoxidation, whereas the ether was formed by direct substitution. Substituent effects on the reaction rates, as well as the effects of NaOMe concentration on the rate and product ratio for both reactions of PhCOCH2Br and PhCOCH2Cl are in line with the mechanism that the alcohol and ether products were formed via two independent and concurrent routes, carbonyl addition and α-carbon attack, respectively, and thus the reaction mechanism could be different from the bifurcation mechanism previously predicted for the reaction of PhCOCH2Br by a simulation study in the gas phase.

Synthesis of Octopus Type Trimethylene Glycol β-D-glucopyranosides

ABSTRACT The octopus type oligo-hydroxypropylene glycol β-D-glucopyranosides were successfully synthesized in this studies: the sterospecific compound of allyl 2, 3, 4, 6-tetra-O-acetyl-β-D-glucopyranosides (1) was deacetylated with NaOMe in MeOH lead to allyl-β-D-glucopyranoside (2) which was perallylated and followed by hydroboration and subsequent oxidation afforded (3-hydroxy-propyl) 2, 3, 4, 6-tetraO(3-hydroxy-propyl)- β-D-glucopyranoside (4). As a result, not only allylpropylene glycol β-D-glucopyranosides (5, 7, and 9) but also hydroxypropylene glycol β-D-glucopyranosides (6, 8, and 10) were synthesized by repeated sequential perallylation followed by hydroboration/oxidation. Keywords : hydroboration/oxidation, perallylation, oligo-hydroxypropylene glycol β-D-glucopyranosides 1. INTRODUCTION Carbohydrates are naturally occurring abund-ant compounds that have been widely studied for a plethora of applications (Hanessian, 1983; Scott, 1994; Middleton et al., 1993). Of parti-cular interest has been their use as polyfunctional molecules for the design and/or synthesis of car-bohydrate-centered multivalent glycoclusters and glycodendrimers (Lindhorst et al., 1998; Lind-horst et al., 2001; Lindhorst et al., 2006). Most of them are based on a multi-step synthesis con-sisting of oligo-glycosylation in order to achieve a uniform O-hydroxy-spacer, such as ethylene or propylene glycol not only in the 2, 3, 4, 6-tetra hydroxy groups but also at the α-anomeric po-sition, turning them into carbohydrate-centered cluster glycosides (Lindhorst et al., 1998; Lind-horst et al., 2001; Lindhorst et al., 2006).Thus, it became our goal to attempt the syn-thesis of the exhaustive glycosylation of octopus type β-D-glucopyranosides. This could provide us with a great potential opportunity of a novel class of high-molecular weight monosaccharide mimetics, which could possibly be adapted for the generation of various spacers with different

Syntheses, molecular structures, and antiviral activities of 1- and 2-(2′-deoxy-d-ribofuranosyl)cyclohepta[d][1,2,3]triazol-6(1H)-ones and 1-(2′-deoxy-d-ribofuranosyl)cyclohepta[b]pyrrol-8(1H)-one

The synthesis of a novel class of 2′-deoxyribonucleosides possessing tropone-fused nitrogen heterocycles as nucleobases was developed. The reaction of alkali metal salts of 1H-cyclohepta[d][1,2,3]triazol-6-one with 2-deoxy-3,5-di-O-(p-toluoyl)-α-d-ribofuranosyl chloride (α-chlorosugar) afforded an anomeric mixture of N1- and N2-coupled glycosylation products. Good stereospecificity in relation to the amount of the β-anomer was achieved in the less polar solvent DME. The reactions of the sodium salt of 1H-cyclohepta[b]pyrrol-8-one and its 3-methyl derivative with an α-chlorosugar in DME gave the β-anomer of the N1-coupled glycosylation products. The glycosylation products were treated with NaOMe in MeOH to produce the desired 2′-deoxyribonucleosides. X-ray structural analyses of the three nucleosides prepared confirmed their anomeric configuration and revealed that their sugars were puckered. The β-anomers of the nucleosides had weak antiviral activities for herpes simplex virus type 1 and herpes simplex virus type 2 in comparison with those of acyclovir (ACV). These nucleosides showed no cytotoxicity on a lung (A549) and two colon (HT-29 and HCT-116) cancer cell lines.

ChemInform Abstract: A Synthetic Approach to Anhydroketopyranoses Having a 6,8‐Dioxabicyclo[3.2.1]octane Structure from Ketopyranoses.

AbstractThe compounds (III) and (VIII) are quantitatively converted to the corresponding compounds (IV) and (IX) by using NaOMe in MeOH.

Synthesis and properties of a novel nucleoside derivative possessing a 2,3,5,6-tetraazabenzo[cd]azulene skeleton

Abstract We describe herein the synthesis and properties of the novel nucleoside derivative, 4,7-diamino-2-(2-deoxy-β- d -erythro-pentofuranosyl)-2,6-dihydro-7H-2,3,5,6-tetraazabenzo[cd]azulene (1). The palladium catalyzed cross-coupling reaction of 2,4-diamino-5-iodo-7-(2-deoxy-β- d -erythro-pentofuranosyl)pyrrolo[2,3-d]pyrimidine (9) with acrylonitrile afforded 2,4-diamino-5-[(E)-1-cyano-2-ethenyl]-7-(2-deoxy-β- d -erythro-pentofuranosyl)pyrrolo[2,3-d]pyrimidine (10) in 77% yield, which was treated with NaOMe in MeOH in the presence of NaSPh to give the desired 1 in 64% yield. Whereas 1 was stable in concentrated ammonia at room temperature, it was gradually hydrolyzed in water to give 4-amino-2-(2-deoxy-β- d -erythro-pentofuranosyl)-2,6-dihydro-7H-2,3,5,6-tetraazabenzo[cd]azulen-7-one (12). Density functional calculations indicated that 12 was 20 kcal/mol more thermodynamically stable than 1 in a model study.

ChemInform Abstract: Nucleophilic Displacement in Polyhalogenoaromatic Compounds. Part 14. Chloroazulenes.

Methoxydechlorination of 5,6-dichloroazulene in NaOMe–MeOH shows second-order kinetics, apparently proceeding by the SNAr mechanism in which the attack of the nucleophile, and not the loss of chloride ion, is rate-determining. No evidence of a Meisenheimer-type intermediate is found. The rate of the reaction is not affected by light, nor by the presence of nitrobenzene; radical contributions to the process are therefore unlikely. The corresponding reactions of 4,5,6,7- and 1,3,5,6-tetrachloroazulene, and of 1- and 3-nitro-5,6-dichloroazulene all show second-order kinetics and are all accelerated compared to the parent compound; 1,3,4,5,6,7-hexachloroazulene reacted too rapidly for measurement. As expected, the extent of such acceleration is conditioned not only by the nature of the substituent but also by its position. Unexpectedly, chlorine substituent effects are clearly greater from the five-membered ring than from the ring undergoing attack.Semi-empirical all-valence-electron SCF–MO calculations are presented which rationalise the orientation of attack and describe the observed substituent effects.

Modular Synthesis of 5-Substituted Thiophen-2-yl C-2′-Deoxyribonucleosides

A new modular methodology of preparation of 5-substituted thiophene-2-yl C-nucleosides was developed. A Friedel-Crafts-type of C-glycosidation of 2-bromothiophene with toluoyl-protected methylglycoside 2 gave the desired protected 1beta-(5-bromothiophen-2-yl)-1,2-dideoxyribofuranose 4a in 60%. The key intermediate 4a was then subjected to a series of palladium-catalyzed cross-coupling reactions. The cross-coupling reactions with alkyl organometallics gave beta-(5-alkylthiophen-2-yl)-2-deoxyribonucleosides 4 and 7 in moderate yields accompanied by side-products of reduction. On the other hand, cross-couplings with arylstannanes proceeded smoothly to give a series of beta-(5-arylthiophen-2-yl)-2-deoxyribonucleosides 4 in good yields. Deprotection of toluoylated nucleosides by NaOMe in MeOH and silylated nucleosides by Et 3N.3HF gave a series of free C-nucleosides 6. Alternatively, other types of 5-arylthiophene C-nucleosides 6 were prepared in one step by the aqueous-phase cross-coupling reactions of unprotected 1beta-(5-bromothiophen-2-yl)-1,2-dideoxyribofuranose with boronic acids. Title 5-arylthiophene C-nucleosides 6 exhibit interesting fluorescent properties with emission maxima varying from 339 to 396 nm depending on the aryl group attached.

Assessment of synthetic methods for the preparation of N-β- d-glucopyranosyl-N′-substituted ureas, -thioureas and related compounds

Preparation of O-peracetylated N-β- d-glucopyranosyl- N′-acyl urea derivatives resulted in the formation of anomeric mixtures under the following conditions: acylation of O-peracetylated β- d-glucopyranosyl urea by acyl chlorides in the presence of ZnCl 2 in refluxing CHCl 3; addition of O-peracetylated β- d-glucopyranosylamine to acyl isocyanates in acetonitrile at rt; addition of carboxamides to in situ prepared O-peracetylated β- d-glucopyranosyl isocyanate in refluxing toluene. Deprotection of O-peracetylated N-β- d-glucopyranosyl- N′-acyl ureas either under base (NaOMe in MeOH at or below rt) or under acid (KHSO 4 or AcCl in MeOH at rt) catalyzed transesterification conditions resulted in unavoidable partial cleavage of the N′-acyl moieties. Reaction of β- d-glucopyranosylammonium carbamate with an isocyanate, isothiocyanate or isoselenocyanate in dry pyridine at rt appears as a general method for the preparation of the corresponding β- d-glucopyranosyl ureas, -thio- and -selenoureas, respectively, inclusive N′-acyl derivatives.

Some transition metal complexes derived from mono- and di-ethynyl perfluorobenzenes

Transition metal alkynyl complexes containing perfluoroaryl groups have been prepared directly from trimethylsilyl-protected mono- and di-ethynyl perfluoroarenes by simple desilylation/metallation reaction sequences. Reactions between Me(3)SiC[triple bond, length as m-dash]CC(6)F(5) and RuCl(dppe)Cp' [Cp' = Cp, Cp*] in the presence of KF in MeOH give the monoruthenium complexes Ru(C[triple bond, length as m-dash]CC(6)F(5))(dppe)Cp' [Cp' = Cp (); Cp* ()], which are related to the known compound Ru(C[triple bond, length as m-dash]CC(6)F(5))(PPh(3))(2)Cp (). Treatment of Me(3)SiC[triple bond, length as m-dash]CC(6)F(5) with Pt(2)(mu-dppm)(2)Cl(2) in the presence of NaOMe in MeOH gave the bis(alkynyl) complex Pt(2)(mu-dppm)(2)(C[triple bond, length as m-dash]CC(6)F(5))(2) (). The Pd(0)/Cu(i)-catalysed reactions between Au(C[triple bond, length as m-dash]CC(6)F(5))(PPh(3)) and Mo( identical withCBr)(CO)(2)Tp* [Tp* = hydridotris(3.5-dimethylpyrazoyl)borate], Co(3)(mu(3)-CBr)(mu-dppm)(CO)(7) or IC[triple bond, length as m-dash]CFc [Fc = (eta(5)-C(5)H(4))FeCp] afford Mo( identical withCC[triple bond, length as m-dash]CC(6)F(5))(CO)(2)Tp* (), Co(3)(mu(3)-CC[triple bond, length as m-dash]CC(6)F(5))(mu-dppm)(CO)(7) () and FcC[triple bond, length as m-dash]CC[triple bond, length as m-dash]CC(6)F(5) (), respectively. The diruthenium complexes 1,4-{Cp'(PP)RuC[triple bond, length as m-dash]C}(2)C(6)F(4) [(PP)Cp' = (PPh(3))(2)Cp (); (dppe)Cp (); (dppe)Cp* ()] are prepared from 1,4-(Me(3)SiC[triple bond, length as m-dash]C)(2)C(6)F(4) in a manner similar to that described for the monoruthenium complexes -. The non-fluorinated complexes 1,4-{Cp'(PP)RuC[triple bond, length as m-dash]C}(2)C(6)H(4) [(PP)Cp' = (PPh(3))(2)Cp (); (dppe)Cp (); (dppe)Cp* ()], prepared for comparison, are obtained from 1,4-(Me(3)SiC[triple bond, length as m-dash]C)(2)C(6)H(4). Spectro-electrochemical studies of the ruthenium aryl and arylene alkynyl complexes - and -, together with DFT-based computational studies on suitable model systems, indicate that perfluorination of the aromatic ring has little effect on the electronic structures of these compounds, and that the frontier orbitals have appreciable diethynylphenylene character. Molecular structure determinations are reported for the fluoroaromatic complexes , , , and .

Formation of Cyclobutylidenepyrazolines by Methanolysis of 6‐(2,3,3‐Trifluorocyclobutenyl)‐4,5‐diazaspiro[2.4]hept‐4‐ene

AbstractThe reaction of 6‐(2,3,3‐trifluorocyclobutenyl)‐4,5‐diazaspiro[2.4]hept‐4‐ene with NaOMe in MeOH results in a mixture of isomeric (6E)‐ and (6Z)‐6‐(2‐fluoro‐3,3‐dimethoxycyclobutylidene)‐4,5‐diazaspiro[2.4]hept‐4‐ene due to the formal substitution of methoxy groups for two geminal fluorine atoms. Both of the isomers selectively add acetyl chloride at the azo‐olefin unit to give 4‐acetyl‐6‐(1‐chloro‐2‐fluoro‐3,3‐dimethoxycyclobutyl)‐4,5‐diazaspiro[2.4]hept‐4‐ene as the trans‐isomer in greater than 95% yield. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2003)

Metal–metal and ligand–ligand interactions in gold poly-yne systems

The acetylide-functionalised thiophene gold(I) complexes [(PPh3)Au(CC(C4H2S)(C4H3S))] 1, [(PPh3)Au(CC(C4H2S)CC)Au(PPh3)] 2, [(PR3)Au(CC(C4H2S)2CC)Au(PR3)] (R = Ph 3, Cy 4) and [(PPh3)Au(CC(C4H2S)3CC)Au(PPh3)] 5 have been prepared by the reaction of the trimethylsilylethynyl oligothiophene with KOH/MeOH, followed by the addition of a stoichiometric amount of the gold(I) phosphine chloride and NaOMe in MeOH. The products have been characterised spectroscopically and their single crystal X-ray structures determined. In the molecular structures of all the complexes the Au(I) centres adopt the expected linear, two-coordinate geometry, except that in 2 the material forms a polymer through additional Au⋯Au interactions [Au⋯Au 3.2915(10) and 3.2347(9) A] between the molecular units. With the longer acetylene-functionalised spacer groups no Au⋯Au interactions are present, but hydrogen bonding and π⋯π interactions are of significance. The solution absorption and emission spectra of these complexes have been recorded and the maxima are increasingly red-shifted as the length and planarity of the functionalised spacer groups increases which is consistent with the absorptions and emissions being dominated by ligand-centred π–π* transitions.

Rearrangement of O-benzoyl-N-(diphenylphosphinothioyl) hydroxylamine: An 18O-labelling investigation of oxygen-sulfur transposition

When Ph 2 P(S)NHOCOPh labelled with 18 O in the CO group (43% isotopic enrichment) reacts with NaOMe in MeOH, the products are unlabelled Ph 2 P(O)NH 2 and labelled PhCO 2 Me (43% isotopic enrichment). By implication, the intermediate Ph 2 P(O)NHSCOPh that results from rearrangement (transposition of O and S atoms) has all the label in the CO group and none in the PO group. Isotopic labelling ( ● = 18 O ) shows that the benzoyl CO group retains its identity in the rearrangement.

Diiron(III) and polymeric iron(III)–sodium complexes with bridging and terminal pyridonate ligands: structures and magnetic properties

The reaction of anhydrous iron(III) chloride or [NEt4]2[Fe2Cl6O] with equimolar quantities of 6-chloro-2-pyridone (Hchp) and NaOMe in MeOH afforded, after recrystallisation from tetrahydrofuran (thf), the one-dimensional polymer [{Fe(µ-chp)6Na3(µ-MeOH)6·2thf}n]1. When the reaction of FeCl3 with NaOMe and Hchp was performed in the presence of 4,4′-dimethyl-2,2′-bipyridine (dmbipy) or 1,10-phenanthroline (phen) the dinuclear complexes [Fe2(µ-OMe)2(chp)4(dmbipy)2]·2MeOH 2 or [Fe2(µ-OMe)2(chp)4(phen)2]·2MeOH 3 resulted. The molecular structures at 150 K and magnetic properties between 1.8 and 280 K of 1–3 have been investigated. Complex 1 displays magnetic behaviour consistent with a paramagnet while 2 and 3 exhibit antiferromagnetic exchange interactions between the spins of the iron(III) ions through OMe bridges (J=–26.8 to –28.6 cm–1).

Synthesis of 3-acetyl-2-amino-4-pyridone

A method hxsynthesizing 3-acetyl-2-amino-4-pyyridone has been suggested. The synthesis involves the condensation of dimethylformamide dimethylacetal at the NH2 group of diphenylboron chelate diacetylketene aminal followed by its intramolecular cyclization under the action of NaOMe in MeOH.

A novel ring cleavage and recyclization of N-cyanomethyl-1,2,3,4-tetrahydroisoquinolinium methiodides: A biomimetic synthesis of litebamine

Summary Treatment of N-cyanomethyl-6-hydroxy-1.2,3,4-tetrahydroisoquinolinium methiodide (1) with NaOMe in MeOH caused C1-N fission and simultaneous recyclization to give 8-hydroxy-5-methoxymethyl-1,2,3,4-tetrahydroisoquinoline (2). By using of the rearrangement synthesis of litebamine (4) was carried out.

Nucleophilic additions to the chiral rhenium alkene complexes [Re(η5-C5H5)(NO)(PPh3)(H2CCHR)]BF4(R = H, Me, CH2CH2Me, Ph or CH2Ph): regio-, diastereo- and enantio-selectivities

Reactions of alkene complexes [Re(η5-C5H5)(NO)(PPh3)(H2CCHR)]BF41(R = H a, Me b, CH2CH2Me c, Ph d or CH2Ph e) and LiCuMe2 in tetrahydrofuran (thf) at –80 °C gave the primary, β-branched alkyl complexes [Re(η5-C5H5)(NO)(PPh3)(CH2CHMeR)]2(79–99%). No secondary alkyl complexes derived from additions to the unsubstituted CH2 termini were detected. Product diastereomer and enantiomer ratios matched those of the reactants. Thus, the additions are regiospecific, diastereospecific and enantiospecific. A chemical correlation involving [Re(η5-C5H5)(NO)(PPh3){CH2CH(CD3)Me}] and a crystal structure determination [(SR,RS)-2e·0.5C6H14] show that attack occurs on the CC face anti to the rhenium. Reactions of 1a or 1b(in thf) with NaOMe–MeOH gave predominantly the 2-methoxyalkyl complexes [Re(η5-C5H5)(NO)(PPh3){CH2CH(OMe)R}](R = H 4a or Me 4b)(92–97%). Analogous reactions of 1c or 1d gave 81–77:19–23 mixtures of 4c or 4d and the alkenyl complexes (E)-[Re(η5-C5H5)(NO)(PPh3)(CHCHR)](85–71%). A similar reaction of 1e gave mainly the allyl complex [Re(η5-C5H5)(NO)(PPh3)(CH2CHCHPh)].

Syntheses of glycyrrhetic acid alpha-diglycosides and enol alpha-glycosides.

Glycyrrhetinate alpha-monoglycoside derivatives 8, 10 and 12, all having a trichloroacetyl group at the C-2 position of the pyranose ring, were treated with NH3-saturated ether at 0 degrees C to give the corresponding alcohols 13, 15 and 17, accompanied by 2'-chloroderivatives, 14, 16 and 18, respectively. Glycosylations of the alcohols 13, 15 and 17 with methyl 2,3,4-tri-O-acetyl-alpha-D-glucuronatopyranosyl bromide 19 in the presence of AgOTf in dry CH2Cl2 gave the corresponding alpha-diglycosides 20, 22 and 24 together with the enol alpha-glycosides 21, 23 and 25, respectively. Glycosylations of the diglycoside derivatives 20, 22 and 35 having no reactive OH group in the molecules with 19 for longer reaction times gave quantitatively the enol alpha-glycoside derivatives 21, 23 and 36, respectively. Glycosylation of the monoglycoside derivative 37, which has a poorly reactive OH group at the C-4 position on the pyranose ring, with 19 gave an enol alpha-glycoside 38. The mechanism of the formation of enol alpha-glycosides was investigated. Removal of the protecting groups of 20, 22 and 24 by successive treatment with 1.5N NaOMe in MeOH and 5% KOH in EtOH-H2O (1:1) gave the free alpha-diglycosides 26-28, and removal of those of 31, 21, 23, 25 and 36 by treatment with 5% KOH in EtOH-H2O (1:1) under reflux gave the free enol alpha-glycosides 41-45, respectively.