Efficient remote axial-to-central chirality transfer in enantioselective SmI2-mediated reductive coupling of aldehydes with crotonates of atropisomeric 1-naphthamides

Control of enantioselectivity by remote amide conformation has been studied in SmI2-mediated reductive coupling of aldehydes with the crotonates possessing different 2-substituted 8-methoxy-1-naphthamides. The enantiomers of atropisomeric 8-methoxy-1-naphthamides were prepared through a chemical resolution process, and their absolute stereochemistry was determined by X-ray crystal structural analysis. It was found that the linkage between crotonate and the C2 position of 8-methoxy-1-naphthamides remarkably influenced the efficiency of remote chirality transfer originated from the amide conformation. Among the four crotonates examined, the one derived from 2-hydroxy-8-methoxy-1-naphthamide reacted with pentanal to afford the highest ee of > 99% for the cis-gamma-butyrolactone and in 90% combined yield with a cis/trans ratio of 90:10. We developed a new procedure for attaching the chiral crotonate via the C8 oxygen to a Rink amide resin under mild conditions and obtained the same level of highly remote axial-to-central chirality transfer in the solid-phase reaction.     

Sur l'orientation et les anomalies de l'acetylation des Bz-méthoxy nitro-2 benzofurannes

4-Methoxy-, 5-methoxy- and 7-methoxy-2-nitrobenzofurans have been acetylated via the Friedel-Crafts reaction under the same reaction conditions. 2-Nitrobenzofuran does not undergo acetylation while 6-methoxy-2-nitrobenzofuran only produces decomposition products. As a result of the positive acetylation reactions, 7-acetyl-4-methoxy-, 4-acetyl-5-methoxy- and 4-acetyl-7-methoxy-2-nitrobenzofuran have been prepared. As side products in the acetylation reactions, 4-methoxy-3-(4′-methoxy-2′-nitro-7′-benzofuranyl)-2,3-dihydrobenzofuran-2-one was isolated when 4-methoxy-2-nitrobenzofuran was the starting material and, likewise, when 5-methoxy-2-nitrobenzofuran was the starting material, 3-chloro-5-methoxy-2,3-dihydrobenzofuran-2-one was obtained. Furthermore, 5-methoxy-2-nitrobenzofuran participated in an unexpected chlorination leading to 4-chloro-5-methoxy-2-nitrobenzofuran.     

A convergent approach to huperzine A and analogues

We describe a concise and convergent synthesis of (rac)-5-methoxy-6-azatricyclco[7.3.1.0(2,7)]trideca-2(7),3,5,11-tetraen-13-ol, which has the basic ring system of huperzine A, a potent inhibitor of acetylcholinesterase. We also describe the synthesis of the novel system 5-methoxy-6-azatricyclo[7.2.2.0(2,7)]trideca-2(7),3,5-trien-10-one and a series of related systems.     

Ring-closing metathesis for the synthesis of substituted indenols,indenones, indanones and indenes: Tandem RCM-dehydrogenative oxidation and RCM-formal redox isomerization

A number of substituted indenols have been synthesized using ruthenium-mediated ring-closing metathesis (RCM) with Grubbs second generation catalyst as the key step. The required dienes were synthesized by two strategies. The first entailed the isomerization of 2-allyl-3-isopropoxy-4-methoxybenzaldehyde to its styrene derivative, isopropoxy-4-methoxy-2-propenylbenzaldehyde using [RuClH(CO)(PPh₃)₃]. This compound and 3-isopropoxy-4-methoxy-2-(1-phenyl-propenyl)-benzaldehyde were then treated with vinyl- or isopropenyl-magnesium bromide to afford four of the scaffolds required for the metathesis. As the compound 3-isopropoxy-4-methoxy-2-(1-methyl-2-propenyl)benzaldehyde proved to be difficult to isomerize, the diene substrates 1-[3-isopropoxy-4-methoxy-2-(1-methylpropenyl)-phenyl]-prop-2-en-1-ol and 1-[3-isopropoxy-4-methoxy-2-(1-methylpropenyl)-phenyl]-2-methylprop-2-en-1-ol were synthesized by the addition of the Grignard reagents to 3-isopropoxy-4-methoxy-2-(1-methyl-2-propenyl)benzaldehyde, followed by isomerization of the arylallyl group to the thermodynamically favoured isomer with potassium t-butoxide. The use of harsher conditions (higher temperature and catalyst loadings) for the metathesis reactions resulted in the formation of substituted indenones, formed by a tandem RCM-dehydrogenative oxidation in the absence of a hydrogen acceptor. Further manipulations of the reaction conditions generated two substituted indanones by way of a tandem RCM-formal redox isomerization sequence. Finally the synthesis of some substituted indenes was accomplished from their corresponding dienes by the use of RCM.     

Synthesis, stability and optimized photolytic cleavage of 4-methoxy-2-nitrobenzyl backbone-protected peptides

We demonstrate the potential of 4-methoxy-2-nitrobenzyl as a Boc chemistry-compatible fully reversible backbone modification for synthetic peptides.     

PLE and HLE catalyzed reverse enantiomeric separation of (±)-methyl-2-methoxy-1-methyl-2,5-cyclohexadiene-1-carboxylate derivatives

We describe the diversities of hydrolase-type enzymes PLE and HLE on the hydrolysis of (±)-methyl-2-methoxy-1-methyl-2,5-cyclohexadiene-1-carboxylate and (±)-methyl-2-methoxy-1-methyl-2,5-cyclohexadiene-4-one-1-carboxylate to afford both enantiomers with 92–96% ee.     

Microwave-mediated Claisen rearrangement followed by phenol oxidation: a simple route to naturally occurring 1,4-benzoquinones. The first syntheses of verapliquinones A and B and panicein A

The naturally occurring 1,4-benzoquinones 2-methoxy-6-propyl-1,4-benzoquinone (1), 2-methoxy-6-pentyl-1,4-benzoquinone (primin 2), 2-methoxy-6-pentadecyl-1,4-benzoquinone (3), 2-methoxy-6-heptadecyl-1,4-benzoquinone (dihydroirisquinone, pallasone B; 4) were synthesized by a simple protocol involving microwave accelerated Claisen rearrangement of allyl ethers 10, followed by hydrogenation of the side chain alkene, and oxidation to the quinone. The Claisen-based methodology was extended to the first synthesis of the marine benzoquinones verapliquinones A and B (5 and 6), and panicein A (7). Isoarnebifuranone (9) was also synthesized by a similar strategy.     

Synthetic studies of the antitumor antibiotic streptonigrin. I. Synthesis of the A-B ring portion of streptonigrin

Bromination of 6-methoxy-5,8-quinolinedione gave the 7-bromo derivative in quantitative yield. Treatment of the bromo compound with sodium azide followed by hydrogenation yielded 7-amino-6-methoxy-5,8-quinolinedione, the A-B ring portion of the antitumor antibiotic strep tonigrin. The corresponding 2-methyl homolog was prepared in a similar manner from 6-methoxy-2-methyl-8-nitroquinoline, which in turn, was obtained by a Skraup synthesis from 2-nitro-anisidine and crotonaldehyde.     

Synthesis and dehydration reaction of 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphth-2-ol: possible intermediate of Lasofoxifene

The paper deals with a simple and sufficient synthesis of key precursor of Lasofoxifene. The 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-3,4-dihydronaphthalene was prepared by a sequence of five reactions steps: first 1-(4-benzyloxyphenyl)-6-methoxy-3,4-dihydronaphthalene was prepared (70%), and this was quantitatively epoxidized to 7b-[4-(benzyloxy)phenyl]-5-methoxy-1a,2,3,7b-tetrahydronaphtho[1,2-b]oxirene. Catalytic (ZnI₂) isomerization of the epoxide gave 1-(4-benzyloxyphenyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-2-one (75%). Its subsequent reaction with phenylmagnesium bromide gave 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,2,3,4-tetrahydro-2-naphthol (87%). Acid-catalysed dehydration of this alcohol by polyphosphoric acid (25°C) provides 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,4-dihydronaphthalene (80%). Dehydration in the system of acetic anhydride/polyphosphoric acid gives 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-3,4-dihydronaphthalene (66%).     

Alkyl Esters of 2-[5-Chloro(bromo)-6-methoxy-4-methylpyrimidinyl-2-oxy]alkanoic Acids

The reaction of a mixture of formaldehyde and sodium cyanide or of lactic acid nitrile with trimethyl(6-methoxy-4-methylpyrimidinyl-2)ammonium chloride give the 2-(6-methoxy-4-methylpyrimidinyl-2-oxy)alkanoic acid nitriles. They were subsequently converted to the corresponding alkyl esters by a Pinner reaction and then to their 2-(5-halo-6-methoxy-4-methylpyrimidinyl-2-oxy) derivatives using N-halosuccinimides.     

Synthesis of carbazomycin B by radical arylation of benzene

Iodination of 2-methoxy-3,4-dimethyl-5-nitrophenol followed by acetylation yields (6-iodo-2-methoxy-3,4-dimethyl-5-nitrophenyl) acetate. Reduction with iron and acetic acid followed by reaction with methyl chloroformate then provides N-methoxycarbonyl-3-acetoxy-2-iodo-4-methoxy-5,6-dimethylaniline. Treatment of this substance in benzene at reflux with tributyltin hydride and a catalytic quantity of diphenyl diselenide leads to the formation of N-methoxycarbonyl-3-acetoxy-2-(2,5-cyclohexadienyl)-4-methoxy-5,6-dimethylaniline which on exposure to phenylselenenyl bromide affords a phenylselenenyl tetrahydrocarbazole. Oxidation deselenation and rearomatization are achieved by heating with tert-butylhydroperoxide finally affording carbazomycin B after saponification.     

Synthesis of 2-(6-Methoxy-2-Quinolyl) Chromone Derivatives

In the continuous investigation of structure and activity correlation of flavonoids, several 2′-hydroxy-2-6(6-methoxy-2-quinolyl)chromone derivatives and their intermediates 2′-hydroxy-2-(6-methoxy-2-quinolyl)acrylophenones were synthesized by the condensation of 6-methoxy-2-quinoline aldehyde with appropriate 2-hydroxoxy-acetophenones in the presence of alcoholic potassium hydroxide, and then oxidized by selenium dioxide.     

Addition-Rearrangement of Aryl- and Alkoxysulfonyl Isocyanates with 5-Methyl-Substituted 3,4-Dihydro-2-methoxy-2H-pyrans. Selective Synthesis of Functionalized 2-Piperidones(1)

3,4-Dihydro-2-methoxy-5-methyl-2H-pyran and 3,4-dihydro-2-methoxy-5,6-dimethyl-2H-pyran undergo addition-rearrangement reactions with arylsulfonyl isocyanates to generate the corresponding 3-formyl- and 3-acetyl-6-methoxy-3-methyl-1-(arylsulfonyl)-2-piperidones. For example, 3,4-dihydro-2-methoxy-5-methyl-2H-pyran and phenylsulfonyl isocyanate afforded 3-formyl-6-methoxy-3-methyl-1-(phenylsulfonyl)-2-piperidone as a separable trans/cis mixture in high yield. The more reactive phenoxysulfonyl and alkoxysulfonyl isocyanates provided analogous results.     

Cyclization of 2-methoxy-6-(substituted benzyloxy)acetophenone hydrazones in the presence of polyphosphoric acid(PPA)

Cyclization of 2-methoxy-6-benzyloxy acetophenone hydrazone gave 3-methyl-4-meth-oxy indazole and 3-methyl-4-methoxy-7-benzyl indazole in the presence of polyphosphoric acid(PPA).The hydrazone was probably converted to 2-hydroxy-6-methoxy acetophenone hydra-zone and 2-hydroxy-3-benzyl-6-methoxy acetophenone hydrazone followed by cyclization to thecorresponding indazoles in acidic conditions.Cyelization of 2-methoxy-6-(halo or alkyl or arylbenzyloxy)acetophenone hydrazones gave similar products.Cyclization of 2-methoxy-6-(p-nitrobenzyloxy)acetophenone hydrazone gave 2-(p-nitrophenyl)-3-methyl-4-methoxy benzo-furan and 3-methyl-4-methoxy indazole while 2-methoxy-6-(m-nitrobenzyloxy)acetophenonehydrazone gave 3-methyl-4-methoxy indazole,3-methyl-4-methoxy-7-(m-nitrophenyl)indazole and3-methyl-4-(m-nitrobenzyloxy)indazole.     

Condensation of 2-(3,4-dihydro-6-methoxy-1-naphthyl)-ethenol acetate with 3,5-dimethyl-3-cyclopentene-1,2-dione

Summary The diene condensation of 2-(3,4-dihydro-6-methoxy-1-naphthyl)ethenol acetate (I) with 3,5-dimethyl-3-cyclopentene-1,2-dione (II) goes structurally specifically with formation of an adduct of the steroid type with functional groups in normal positions and an angular methyl group.We are deeply grateful to Prof. Buchta (Erlangen University) for the provision of a sample of 2-ethyl-7-methoxy-1-methylphenanthrene.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1051–1058, June, 1965     

A new approach to the synthesis of conjugated polymer-nanocrystal composites for heterojunction optoelectronics

We report a simple one pot process for the preparation of lead sulfide (PbS) nanocrystals in the conjugated polymer poly (2-methoxy-5-(2'ethyl-hexyloxy)-p-phenylene vinylene)(MEH-PPV), and we demonstrate electronic coupling between the two components.     

Determination of residual solvents and reagents in X-ray contrast media by automatic static headspace capillary gas chromatography

A specific, sensitive, and simple method for the quantitation of residual methanol, 2-propanol, 2-butanol, 2-methoxy-1-ethanol, 1-chloro-3-methoxy-2-propanol, 3-chloro-2-methoxy-1-propanol, and 1,3-dimethoxy-2-propanol in two non-ionic X-ray contrast media, has been developed. The headspace of a 25 % w/V aqueous solution of contrast media, obtained at 90–110°C in 15 min, was injected onto a capillary column coated with cyanopropyl, phenyl, dimethylpolysiloxane polymer. The internal standards used were 2-pentanol and 3-methoxy-1-butanol. The limits of detection were below 5 μg/g. The repeatability of the method at 50 μg/g of each solvent was below 5 %; and at 100 μg/g of the methoxypropanol compounds and 2-methoxy-1-ethanol, below 10 % (RSD, N = 5).     

The practical synthesis of (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthylamine via optical resolution of 2-(3-methoxybenzyl)succinic acid

We describe the practical synthetic route for (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthylamine 1(2S)-2-amino-7-methoxytetraline; (S)-AMT]. (2R)-2-(3-Methoxybenzyl)succinic acid [(R)-1] was obtained by the optical resolution of 2-(3-methoxybenzyl)succinic acid (1) as the salt of (1R,2S)-2-(benzylamino)cyclohexylmethanol (7), and (R)-1 was converted to the optically active (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthoic acid [(S)-2] by the intramolecular Friedel-Crafts reaction followed by catalytic hydrogenation. (S)-AMT was obtained from the acid (S)-2 by Hofmann rearrangement without racemization.     

Ultrafiltration and Pyrolysis Gas Chromatography Mass Spectrometry of Chlorolignins in Pulp Mill Effluent

Abstract

Investigations on the effluent of a German pulp mill on the river Rhine using ultrafiltration and pyrolysis gas chromatography mass spectrometry have shown the presence of several chlorinated 2-methoxyphenols, which probably originate from chlorinated lignin or lignosulfic acid. Chlorinated phenolic pyrolysis products identified were 2-methoxy-6-chlorophenol, 2-methoxy-4-methyl-6-chlorophenol, 2-methoxy-dichlorophenol, 2-methoxy-4-vinyl-6-chlorophenol, 2-methoxy-4-(chloropropyl)phenol, 2-methoxy-4-(prop-2-enyl)-6-chlorophenol, 2-methoxy-4-(propan-2-one)-6-chlorophenol, 2-methoxy-3, 5, 6-trichlorophenol, 2-methoxy-4-vinyl-3, 5, 6-trichlorophenol. Monochlorinated 2-methoxyphenols were the dominant chlorinated pyrolysis products, smaller amounts of di- and trichloromethoxyphenols were also detected. 2-Methoxyphenols (guaiacols) were the dominant lignin pyrolysis products, only small amounts of 2, 6-dimethoxyphenols (syringols) were detected. This indicates the origin from soft wood. A Py-(GC)-(MS)-TIC-chromatogram of reference spruce milled wood lignin is comparable with the TIC-chromatogram of pulp mill effluent MW-fraction > 10,000, showing many similar compounds. The ultrafiltration fraction 1000 < MW < 10,000 showed a remarkably empty TIC-chromatogram, with 2-methoxyphenol and 2-methoxy-6-chlorophenol as the only significant phenolic peaks. This may indicate a high degree of oxidation/chlorination of lignin in this fraction.     

Isothermal vapour–liquid equilibria in the binary and ternary systems composed of 2-propanol, diisopropyl ether and 1-methoxy-2-propanol

Vapour pressures for 1-methoxy-2-propanol are reported as well as the vapour–liquid equilibrium data in the two binary 2-propanol + 1-methoxy-2-propanol, and diisopropyl ether + 1-methoxy-2-propanol systems, and in the ternary 2-propanol + diisopropyl ether + 1-methoxy-2-propanol system. The data were measured isothermally at 330.00 and 340.00 K covering the pressure range 5–98 kPa. The binary vapour–liquid equilibrium data were correlated using the Wilson, NRTL, and Redlich–Kister equations; resulting parameters were then used for calculation of phase behaviour in the ternary system and for subsequent comparison with experimental data.