Sodium Methoxide In Methanol Research Articles

Reduction of Five-Membered .ALPHA.,.BETA.-Unsaturated Lactones and Related Compounds with the Ni2+/BH4- System.

The reductions of an α, β-unsaturated lactone (5) and lactam (7) with the Ni2+/BH-4 system resulted in the formation of cis-hydrogenated products (8a and 9a) with high stereoselectivity. The cis products (8a and 9a) were easily isomerized to the corresponding trans isomers (8b and 9b, respectively) by refluxing with sodium methoxide in anhydrous methanol. Isotope labeling studies with methyl cinnamate as the substrate indicated that the reduction with this reducing system poceeds stepwise via a carbon-nickel intermediate.

ChemInform Abstract: Phosphorus‐Nitrogen Compounds. Part 62. The Reactions of 2,2‐Diamino‐4,4,6,6,8,8‐hexachloro‐ (III) and 2,6‐Diamino‐2,4,4,6,8,8‐hexachlorocyclotetraphosphazatetraene (II) with Sodium Methoxide in Methanol. The First Example of Amino Group Migration in the Tetramer System. 31P, 1H, and 13C NMR Spectroscopic Investigations of the Products.

ChemInform Abstract: Phosphorus‐Nitrogen Compounds. Part 62. The Reactions of 2,2‐Diamino‐4,4,6,6,8,8‐hexachloro‐ (III) and 2,6‐Diamino‐2,4,4,6,8,8‐hexachlorocyclotetraphosphazatetraene (II) with Sodium Methoxide in Methanol. The First Example of Amino Group Migration in the Tetramer System. 31P, 1H, and 13C NMR Spectroscopic Investigations of the Products.

Photolabile, spacer-modified oligosaccharides for probing malto-oligosaccharide binding sites in proteins

O-Deacylation and S-deacylation of the diastereomers of 2-azido-4- S-benzoyl-4-mercaptobutyl 2,3,4,6-tetra- O-acetyl-α- d-glucopyranoside ( 9) with methanolic sodium methoxide and coupling of the resulting thiol to methyl 3,4-anhydro-6-deoxy-β- l- arabino-hex-5-enopyranoside ( 2) gave the corresponding diastereomers of the spacer-modified disaccharide methyl 4- S-(3-azido-4-α- d-glucopyranosyloxybutyl)-6-deoxy-4-thio-α- d- xylo-hex-5-enopyranoside ( 10). Glucosylation of the diastereomers of 10 with α-cyclodextrin-CGTase and treatment of the products with beta-amylase gave the diastereomers of the spacer-modified oligosaccharides methyl 4- S-(3-azido-4-α-maltosyloxybutyl)-6-deoxy-4-thio-α- d- xylo-hex-5-eno pyranosides ( 11) and 4- S-(3-azido-4-α-maltotriosyloxybutyl)-6-deoxy-4-thio-α- d- xylo-hex-5-enopyranosides ( 12). The diastereomers of 10 each had a good affinity for pancreatic alpha-amylase and the maltose-binding protein from E. coli. The affinities of the diastereomers of 11 and 12 were higher by at least one order of magnitude.

ChemInform Abstract: Synthesis of 2‐t‐Butyl‐5‐hydroxypyrimidine via Hydrolysis of 2‐t‐Butyl‐5‐halopyrimidines.

Abstract2‐tert‐Butylpyrimidine (I) reacts with bromine or chlorine to give the 2‐tert‐butyl‐5‐halopyrimidines (II).

Synthesis and antiviral activity of some 7-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine analogs of sangivamycin and toyocamycin

The sodium salt of 4-amino-3-cyanopyrazolo[3,4-d]pyrimidine (1) was condensed with (2-acetoxyethoxy)methyl bromide (2) to provide the corresponding protected acyclic nucleoside, 4-amino-3-cyano-1-[(2-acetoxyethoxy)methyl]-pyrazolo[3,4-d]pyrimid ine (3). Treatment of 3 with sodium methoxide in methanol provided a good yield of methyl 4-amino-1-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine-3- formimidate (4). Treatment of the imidate (4) with sodium hydrogen sulfide gave the thiocarboxamide derivative 5. Aqueous base transformed 4 into 4-amino-1-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine-3- carboxamide (6) in good yield. Treatment of 5 with mercuric chloride furnished the toyocamycin analogue 7. Evaluation of compounds 1, 3-7 revealed that only the heterocycle (1) and the thiocarboxamide acyclic nucleoside (5) were active. Compound 5 was the more potent with activity against human cytomegalovirus and herpes simplex virus type 1.

Location of O-acetyl groups in the heteropolysaccharide of the cactus Pereskia aculeata

The complex polysaccharide of the leaves of Pereskia aculeata is highly branched, containing units of arabinofuranose, arabinopyranose, galactopyranose, galactopyranosyluronic acid, and rhamnopyranose. Glucopyranose units are also present. The location of 25 molar % of acetate ester groups was determined using modified Bouveng procedures, one of the changes being the use of refluxing methanolic sodium methoxide for the removal of N-methyl- N-phenylcarbamoyl groups. With the aid of g.l.c.-m.s. on a capillary column of DB-210, which separated the various isomeric mono-, di-, and tri- O-methyl arabinitol acetates, and by examination of e.i. fragmentation patterns of various derivatives deuterated at C-1, the O-acetyl groups were located. They were found mainly as monosubstituents at O-2 and O-3 of nonreducing arabinofuranosyl end-groups and at O-2 of 4- O-substituted galacto- and gluco-pyranosyl units.

Base-promoted ring-opening and elimination of 4-chloro- and 4-(methylthio)azetidinones

In a search for elimination within the β-lactam ring, reactions of N-phenyl- and N-benzyl-, 4-chloro-, and 4-(methylthio)azetidinones with sodium methoxide in methanol have been investigated. The products formed are enamine esters, consistent with the occurrence of both an elimination reaction and opening of the β-lactam ring. Substituent and leaving-group effects indicate, however, that ring-opening is the first and rate-controlling reaction and that elimination occurs from an initially formed ring-opened intermediate. Thus a small leaving-group rate ratio (k Cl /k SMe ) and insensitivity of the rate to the stereochemistry of cis- and trans-3-(tosyloxy)-4-chloro substituents rule out elimination by a concerted mechanism (E2), while similar substituent effects at the 3- and 4-positions, and reaction at the predicted rate for β-lactam methanolysis, exclude a carbanion mechanism (E1cB)

Anomalous Zemplén deacylation reactions of 2- O-acyl-3- O-alkyl or -3- O-glycosyl derivatives of d-galactose and d-glucose: synthesis of O-α- d-mannopyranosyl-(1→4)- O-α- l-rhamnopyranosyl-(1→3)- d-galactose and an intermediate for the preparation of 2- O-glycosyl-3- O-(α- d-mannopyranosyl)- d-glucoses

Treatment of 2- O-benzoyl ( 1) and 2- O-acetyl ( 5) derivatives of benzyl 4,6- O-benzylidene-3- O-(2,3,4-tri- O-acetyl-α- l-rhamnopyranosyl)-β- d-galactopyranoside under Zemplén conditions (catalytic amount of sodium methoxide in methanol) gave partially deacylated disaccharides in which the 2- O-acyl groups were retained. Likewise, a similar result was obtained with the β- l-rhamnopyranosyl analogue ( 3) of 1. This anomalous reaction was used in a synthesis of the title trisaccharide ( 17) and of methyl 4,6- O-benzylidene-3- O-(2,3:4,6-di- O-isopropylidene-α- d-mannopyranosyl)-α- d-glucopyranoside, an intermediate for the synthesis of 2- O-glycosyl-3- O-(α- d-mannopyranosyl)- d-glucoses.

Synthesis of [5‐14C]pentostatin, an antileukemic agent and potent adenosine deaminase inhibitor

AbstractReaction of triethyl ortho[14C]formate (2) with 2‐amino‐1‐(5‐amino‐1H‐imidazol‐4‐yl)ethanone dihydrochloride (1) in the presence of molecular sieves 4A gave 6,7‐dihydro[5‐14C]imidazo[4,5‐d][1,3]diazepin‐8(3H)‐one hydrochloride monodimethyl sulfoxide (3) (radiochemical yield, 60%). The latter was persilylated with bis(trimethylsilyl)trifluroacetamide (4) and glycosylated with 2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐D‐erythro‐pentofuranosyl chloride (6) to give a mixture from which the 3‐N‐β‐glycosylated product 8 was isolated by chromatography and crystallization (13%). Deprotective saponification with methanolic sodium methoxide and subsequent sodium borohydride reduction of the 8‐keto function gave a (R,S)‐mixture from which the desired (R)‐isomer, [5‐14C]pentostatin (11), was isolated by preparative HPLC over a C18 column, desalting with Diaion‐HP20, and subsequent crystallization (39%).

Septanose Carbohydrates. III. Oxidation-Reduction Products From 1,2-3,4-Di-O-isopropylidene-α-D-glucoseptanose: Preparation of L-Idose Derivatives

Oxidation of 1,2:3,4-di-O-isopropylidene-α-D-glucoseptanose (1a) with dimethyl sulfoxide and acetic anhydride has yielded methylthiomethyl ether (1b), ketone (2), and a novel product (3). Reduction of (2) gave (1a) and its L-ido isomer (4a) which yielded the mono-O-isopropylidene compound (5a) on aqueous acid hydrolysis. Treatment of (5a) with acidified acetone gave (4a) and 1,2:4,5-di-O-isopropylidene-β-L- idoseptanose (7a). Reaction of (2) with methylmagnesium iodide yielded the two 5-C-methyl compounds (8) and (9). Hydrolysis of (8) and (9) gave 5-C-methyl-D-glucose (10) and 5-C-methyl-L-idose (11), respectively, as crystalline compounds which yielded crystalline pentaacetates on acetylation. Treatment of the p-toluenesulfonate (1c) with lithium benzoate in dimethylformamide gave the benzoate of (4a) and an elimination product (17). Reaction of (1c) with sodium methoxide in methanol yielded (17) and the isomeric elimination product (18).

Synthesis of an Epoxide Derivative of Thymidine as a Potential Enzyme Inhibitor

Abstract Attempts to prepare I -[7,8-anhydro-2,5,6-trideoxy-α-L-lyxo-(and β-n-ribo)-octofuranosyl]thymine (10) by treatment of halohydrins 6–9 with sodium hydride in DMF or sodium methoxide in methanol gave mixtures of the epoxides 10 or 11 and the 3′,8′-anhydronucleoside 12. The structure of 12 was confirmed by oxidation to the cyclic ketone 14. The successful synthesis of 10 involved a Wittig reaction on the thymidine-5′-aldehyde 16 to give the unsaturated ketoacetate 18 which was reduced in two steps to the diacetate 20. The 7′-O-tosyl derivative 21 upon treatment with sodium methoxide in chloroform gave the pure epoxide 10 which was marginally toxic to L1210 cells in culture (I50=25 μM) and demonstrated borderline in vivo activity (24% ILS) against P388 murine leukemia.

Synthesis of 2-t-Butyl-5-hydroxypyrimidine via Hydrolysis of 2-t-Butyl-5-halopyrimidines

The hydrolysis of 2-t-butyl-5-halopyrimidine (halogen=bromine or chlorine) with sodium methoxide in methanol yields 2-t-butyl-5-hydroxypyrimidine. The side reaction product, 2-t-butylpyrimidine, is substantially reduced, especially in the case of the bromo derivative, with catalytic amounts of elemental sulfur

Preparation and reactions of epoxy-activated cellulose.

Cellulose acetate fibers were treated with sodium methoxide in methanol for replacing acetyl group with sodium atom. The resulting sodium-contaning cellulose was treated with epichlorohydrine (ECH) in DMSO for preparing epoxy-activated cellulose (CGE). The amount of epoxy group introduced into cellulose increasing with sodium-content but was independent of the reaction time, reaction temperature or ECH concentration. Besides epoxidation, some side reactions occured through ring-opening reaction of epoxy group. CGE could be converted to various functional cellulosic materials through reactions with substances containing active hydrogen, such as amines, amino acids or carboxylic acids. Polyethylenimine (PEI) reacted easily with CGE in DMF. The PEI content of the product and the conversion of epoxy groups increased with decrease in molecular weight of PEI. Other amines such as ammonia, methylamine, dimethylamine or 4-aminopyridine also reacted with CGE. Since methylamine and dimethylamine reacted with CGE in similar ways, the reactivity was considered to be similar with primary and secondary amino groups in PEI. Glycine also reacted with CGE in aqueous solution, and the degree of the reaction increased with increase in pH of the solution. Glycine methyl ester hydrochloride dissolved in DMSO reacted easily with CGE by adding basic compound such as 1, 8-diazabicyclo [5, 4, 0] undecene-7 (DBU). Some carboxylic acids including propionic, n-butyric and succinic acids also reacted readily with CGE, especially in the presence of DBU. However, the reactivity of succinic acid was lower than that of glycine in an aqueous alkaline solution, suggesting that the amino group of glycine was more reactive than the carboxyl group to CGE in aqueous solution.

PHOSPHORUS-NITROGEN COMPOUNDS. PART 62.1 THE REACTIONS OF 2,2-DIAMINO-4,4,6,6,8,8-HEXACHLORO- AND 2,6-DIAMINO-2,4,4,6,8,8-HEXACHLORO CYCLOTETRAPHOSPHAZATETRAENE WITH SODIUM METHOXIDE IN METHANOL. THE FIRST EXAMPLE OF AMINO GROUP MIGRATION IN THE TETRAMER SYSTEM. 31P, 1H, AND 13C NUCLEAR MAGNETIC RESONANCE SPECTROSCOPIC INVESTIGATIONS OF THE PRODUCTS

Abstract The reaction of octachlorocyclotetraphosphazatetraene with aqueous ammonia yields the geminal 2,2- and the nongeminal 2,6-diamides, N4P4Cl6(NH2)2 as well as a trace of the monoamide, N4P4CI7(NH2). The reactions of 2,2-diamino-4,4,6,6,8,8-hexachloro- and 2,6-diamino-2,4,4,6.8,8- hexachloro-cyclotetraphosphazatetraene with sodium methoxide in methanol were studied. The former yields the geminal hexamethoxide, N4P4(NH2)2(OMe)6, a rearranged 2,6-isomer (being the first example of an amino group migration in the tetramer system), and the heptamethoxide, N4P4(NH2)(OMe)7, whilst the latter gives rise to two isomeric 2,6-derivatives, N4P4(NH2)2(OMe)6, together with the heptamethoxide. The 31P, 1H and 13C nuclear magnetic resonance spectra of the products are reported.

Further studies on the moisture‐related properties of hydrolyzed poly(ethylene terephthalate)

AbstractContact angle measurements with water indicate that the hydrophilicity of poly(ethylene terephthalate) (PET) film decreased in the order PET treated with aqueous sodium hydroxide > untreated PET > PET treated with methanolic sodium methoxide. When the sodium‐methoxidetreated polyester was hydrolyzed with caustic soda, its contact angle fell, indicating that the methyl ester groups formed during the sodium methoxide reaction by a base‐catalyzed ester interchange had been the cause of the high contact angles. Thus it appears that carboxyl groups at the surface of hydrolyzed PET play an important role in determining its hydrophilicity. It appears from adsorption experiments that there is a marked increase in the surface area of PET fibers on treatment with aqueous sodium hydroxide. The increase is attributed to the presence of the pits produced by the hydrolysis. It is suggested the higher surface area leads to increased numbers of hydrophilic groups on the fiber surface causing the greater wettability observed in the caustic hydrolyzed samples.

Syntheses of 3-methylpyrrole via methyl 4-methylpyrrole-2-carboxylate. A thermal oxazolone–pyrone rearrangement

3-Ethoxy-2-methylpropenal with hippuric acid and acetic anhydride gave 4-(3-ethoxy-2-methylallyl-idene)-2-phenyloxazol-5(4H)-one. By successive treatment with methanolic potassium hydroxide, acetic–hydrochloric acid, and methanolic sodium methoxide, methyl 4-methylpyrrole-2-carboxylate was formed in high overall yield, and was converted into 3-methylpyrrole by hydrolysis and decarboxylation. The oxazolone with sodium hydroxide in acetone or dioxane gave 4-(3-hydroxy-2-methylallylidene)-2-phenyloxazol-5(4H)-one, isomerized in boiling acetone, or on melting, to 3-benzoylamino-5-methylpyran-2-one. 3-Ethoxy-2-methylpropenal condensed with glycine methyl ester to give an enaminal, cyclized in moderate yield to methyl 4-methylpyrrole-2-carboxylate.

Photocyclisation of 2-aroylquinoxalines; formation of coloured indolo[l,2-a]quinoxalines

Irradiation of 2-benzoylquinoxaline ( 10) and 2-benzoyl-3-methylquinoxaline ( 11) in the presence of trifluoroacetic acid resulted in cyclisation to the orange-red 7-hydroxyindolo-[l,2-a]quinoxalin-5-ium trifluoroacetate ( 16) and the 6-methyl homologue 17 respectively. Similarly, irradiation of quinoxaline 11, 2-benzoyl-3-benzylquinoxaline ( 12), 2-(2,4-dimethylbenzoyl)-3-methylquinoxaline ( 23), and 2-benzoyl-3,6,7-trimethylquinoxaline ( 24) in methanol, or in ether, containing p-toluenesulphonic acid gave orange-red salts; 6-methyl-(18), 6-benzyl- (19), 6,8,10-trimethyl- ( 26), and 2,3,6-trimethyl-7-hydroxyindolo[l,2-a]-quinoxalin-5-ium p-toluenesulphonate ( 27) respectively. The purple photoproduct, 6-methyl- indolo[l,2-a]quinoxalin-7(5 H)-one ( 15) was formed on irradiation of quinoxaline 11 in methanol. The 7-hydroxyindolo[l,2-a]quinoxalinium salts 16, 18, 19 and 27 formed yellow 7-acetoxyindolo[l,2-a]quinoxalines 20,21,22, and 29 respectively, and quinoxalinium salt 26 was converted into 6,8,10-trimethyl-7-propionoxyindolo[l,2-a]quinoxaline ( 28). In aerated methanolic sodium methoxide, the purple photoproduct 15 was converted into l-(2-carboxyphenyl)-3-methylquinoxalin-2(1 H)-one (34).

Synthesis of (±)-3-amino-2,4-dihydroxy-6-hydroxymethyl-8-oxabicyclo[3.2.1]octane derivatives, and their anhydroring-migration with hydrogen bromide-acetic acid

Nitromethane-mediated cyclization of the dialdehyde generated by periodate oxidation of (±)-2 exo,3 exo-dihydroxy-5 endo-hydroxymethyl-7-oxabicyclo[2.2.1]-heptane ( 2) in methanolic sodium methoxide afforded, after neutralisation, three diastereoisomers ( 4a–6a) of (±)-2,4-dihydroxy-6-hydroxymethyl-3-nitro-8-oxabicyclo[3.2.1]octane in 52% combined yield. Their structures were assigned on the basis of 1H-n.m.r. spectra of the respective triacetates ( 4b–6b). Hydrogenation of the nitro compounds in methanol-acetic anhydride with Raney nickel followed by acetylation gave the corresponding N-acetyl derivatives ( 4c–6c), treatment of which with 15% hydrogen bromide-acetic acid at 80° replaced the primary acetoxyl group with bromine, giving the monobromo derivatives 4d–6d. Migration of the anhydro rings also occurred with 4c and 6c, yielding the respective isomers (1 RS,2 RS,4 SR, 5 RS,6 RS,7 SR)-7-acetamido-2,6-diacetoxy-4-bromomethyl-8-oxabicyclo[3.2.1]octane ( 7) and (1 RS,2 RS,4 SR,5 RS,6 SR,7 SR)-6-acetamido-4,7-diacetoxy-2-bromo-methyl-8-oxabicyclo[3.2.1]octane ( 8a). The mechanism of these reactions is considered.

A facile synthesis of 6‐alkoxy‐2,4‐diaryl‐5‐cyanopyridine

AbstractA new synthesis of substituted pyridine is reported. The base catalyzed reaction of substituted chalcones with malononitrile using sodium ethoxide in ethanol at room temperature afforded 2,4‐diaryl‐5‐cyano‐6‐ethoxypyridine. Similarly, 2,4‐diaryl‐5‐cyano‐6‐methoxypyridine have been prepared in presence of sodium methoxide in methanol as a catalyst.

Synthesis and molecular structure of a "lantern" dimer, bis(tetraphenylarsonium) tetrakis(N,N'-ethylenebis(2-mercaptoactamide)dioxoditechnetate(2-)

Reaction of (Bu{sub 4}N)(TcOCl{sub 4}) with a 5-fold excess of N,N{prime}-ethylenebis(2-mercaptoacetamide) (H{sub 4}ema) in methanolic sodium methoxide yielded a blue precipitate which was metathesized to give (AsPh{sub 4}){sub 2}(Tc{sub 2}O{sub 2}(H{sub 2}ema){sub 4}) (1). Complex 1 crystallized as a hexahydrate and was structurally characterized by single-crystal x-ray crystallography. The structure of the dianion showed a centrosymmetric dianion with two square-pyramidal OTcS{sub 4}cores bridged 4-fold by the (H{sub 2}ema{sup 2{minus}}) dithiolate ligands. The metal-oxo groups are oriented into the center of the cage created by the bridging ligands, giving what is referred to as a lantern structure. The intramolecular Tc-Tc* distance was 7.175 (4) {angstrom}, and the distance between the two metal oxo ligands, O1-O1*, was 3.96(2) {angstrom}. The six water molecules per dimer were found to be hydrogen-bonded to each other and to the amide NH and CO groups on the ligands. Compound 1 was converted to (AsPh{sub 4})(TcO(ema)) when heated in solution or when reacted with aqueous base. 19 refs., 3 figs., 5 tabs.