Preparation of 2,3- and 2,5-dihydropyrazine 1,4-dioxides from 2-hydroxyamino-2-methylpropanal oxime and some of their properties

3-Hydroxy-2,3-dihydropyrazine 1,4-dioxide derivatives were obtained by condensation of 2-hydroxyamino-2-methylpropanal oxime with glyoxal, diacetyl, and 1,2-cyclohexanedione in water, and 3-methoxy-2,3-dihydropyrazine 1,4-dioxide was obtained by condensation with diacetyl in methanol. 2,5-Dihydropyrazine 1,4-dioxide is formed when 2-hydroxyamino-2-methylpropanal oxime is heated in a solution of acetone and dilute hydrochloridic acid. The reduction of 3-hydroxy- and 3-methoxy-2,3-dihydropyrazine 1,4-dioxides and 2,5-dihydropyrazine 1,4-dioxide leads to 1,4-dihydroxypiperazines, and the bromination of 3-methoxy-2,3-dihydropyrazine 1,4-dioxide gives 5,6-bis(bromomethyl)-3-methoxy-2,3-dihydropyrazine 1,4-dioxide. 1,4-Dihydroxy-2,5-piperazinedione was obtained by oxidation of 2,5-dihydropyrazine 1,4-dioxide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1414–1418, October, 1983.     

Reactions of 4-Methoxy-3-quinolinyl and 1,4-Dihydro-4-oxo-3-quino-linyl Sulfides Aiming at the Synthesis of 4-Chloro-3-Quinolinyl Sulfides

The preparation of 1,4-dihydro-4-oxo-3′-alkylthio-3,4′-diquinolinyl sulfides 3 or 1,4-dihydro-4-oxo-3-(alkylthio)quinolines 4 by acid catalysed hydrolysis of 4-methoxy-3′-alkylthio-3,4′-diquinolinyl sulfides 1 or 4-methoxy-3-(alkylthio)-quinolines 2 is described. The reactions of 4-methoxy-3′-alkylthio-3,4′-diquinolinyl sulfides 1 or 1,4-dihydro-4-oxo-3′-alkylthio-3,4′-diquinolinyl sulfides 3 with phosphoryl chloride in DMF afforded 4-chloro-3′-alkylthio-3,4′-diquinolinyl sulfides 5 . Treatment of the title compounds 1 or 3 with boiling phosphoryl chloride systems:leads to 4-chloro-3-(alkylthio)quinolines 6 and thioquinanthrene but those of alkoxy- or oxo-quinolines 2 or 4 lead to 4-chloro-3-(alkylthio)quinolines 6 . The reactions of N-methyl-4(1H)-quinolinones 3n and 4n with phosphoryl chloride directed to 4-chloro-3-(alkylthio)quinolines 6 were studied as well.     

A 5-methylthiopenicillin analog and its transformation to novel bicyclic β-lactams

Reaction of methoxyacetyl chloride with 2-methylthio-2-thiazoline resulted in the stereoselective production of one isomer of 6-methoxy-5-methylthiopenam which underwent rearrangement to 6-methoxy-7-methylthio-5-oxo-2,3,4,5-tetrahydro-1,4-thiazepine when treated with trifluoroacetic acid. Subsequent thioamidation and alkylation with methyl iodide provided 5,7-bismethylthio-6-methoxy-2,3-dihydro-1,4-thiazepine which reacted with methoxyacetyl chloride and triethylamine to give a novel 1,4-thiazabicyclo[5.2.0]non-5-ene. Other substituted bicyclic β-lactams of similar structure have also been synthesized.     

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.     

Investigations toward the total syntheses of proapoiphine and homoproaporphine alkaloids

The reaction of 1,2,3,5-telrahydro-6-methoxy-1 -[2-(4-methoxy-1,4-eyelohexadien-1 -yl)eth-yl]-l-methyl-7-isoquinolinol ( 12 ) with hot phosphoric acid afforded (±)-tetrahydro-homoglazio-vine ( 14 ) in good yield. Similar treatment of 1,2,3,4-tetrahydro-6-methoxy-l -[2-(4-methoxy-1,4-cyelohexadien-l-yl)methyl]-2-methyl-7-isoquinolinol ( 13 ) did not produce the desired (±)-tetra-hydroglaziovine ( 18 ) but rather a mixture of diastereomeric 4,5,6,6a?,7,7a?,8,9,11, 11a?-deca-hydro-l-hydroxy-2-metlu>xy-6-methyl-10H-dibenzo[(de,g]quinolin-l-ones (16 and 17) was obtained.     

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%).     

醌型木素模型物的光学特性

为探索醌型木素化学结构与颜色的关系,以五种醌型木素模型物2-甲氧基-1,4-苯醌(I)、1,2-苯醌(II)、4-亚烯丙基-2-甲氧基-2,5-环己二烯酮(亚甲基醌)(III)、5-甲氧基-1,4-苯醌-2-氧负离子(IV)和5-甲基-1,4-苯醌-2-氧负离子(V)作为纸浆中醌型木素发色体的代表,在B3LYP/6-311++G(2d,p)水平上获得了它们在乙醇中的稳定基态构型,采用含时密度泛函理论(TD-DFT)在同等水平上计算了其在乙醇溶液中的电子光谱,并分析了它们在可见光范围内的吸收.结果发现:五种模型物在可见光范围内的吸收均源于电子的π→π*跃迁,它们的最大吸收波长顺序依次为IIIIIIIVV,吸光系数顺序依次为IVIVIIIII;漂白过程中生成的醌氧负离子以及邻醌类模型物具有中等大小的吸光系数(ε=1978-3197),吸收波长较长(445.47-552.36 nm),是漂白后纸浆具有颜色的重要原因.对醌类模型物吸收波长较小(414.91 nm),吸光系数大小为中等(ε=2094),亚甲基醌类模型物虽然吸光系数大(ε=31935),但吸收波长较小(407.90 nm),二者对漂白后纸浆的颜色影响较小.     

Palladium-catalyzed cross-coupling reactions of pyridylboronic acids with heteroaryl halides bearing a primary amine group: synthesis of highly substituted bipyridines and pyrazinopyridines

A range of halogenated aromatics and heteroaromatics bearing a primary amine group are shown to be suitable substrates for Suzuki cross-coupling reactions with arylboronic acids and pyridylboronic acids under standard conditions, without the need for protection/deprotection steps. New amino-substituted arylpyridines, bipyridines, and pyrazinopyridines have thereby been obtained. Conditions for the efficient syntheses of 2-methoxy-5-pyridylboronic acid 1 and 2-methoxy-3-pyridylboronic acid 2 in ca. 75 g batches have been defined. A 2-fold reaction of 2-amino-5-bromopyrazine with 2,5-dimethoxy-1,4-benzenediboronic acid affords 1,4-dimethoxy-2,5-bis[2-(5-aminopyrazyl)]benzene 31. The X-ray crystal structures of 1 and 31.DMF are reported.     

Investigation of nitrogen- and sulfur-containing heterocycles

The reaction of 5-amino-4-chloro- and -4-methoxy-6~mercaptopyrimidines with 4-methoxy-, 4-amino-, and 2,4-diethoxyphenacyl chlorides has yielded 5-amino-4-chloro- and -4-methoxy-6-phenacylthiopyrimidines. The reaction of 2, 5-diamino-4-methyl-6-mercaptopyrimidine with 4-methoxyphenacyl chloride has yielded 2-amino-6-hydroxy-6-(4-methoxyphenyl)-4-methyl-5, 6-dihydropyrimido[4, 5-b]-1,4-thiazine, and that with 4-aminophenacyl chloride has yielded the corresponding 7H-pyrimido[4, 5-b]-1,4-thiazine.For part IV, see [1].     

Utilisation of electrospray time-of-flight mass spectrometry for solving complex fragmentation patterns: application to benzoxazinone derivatives

In this paper we describe the application of electrospray time-of-flight mass spectrometry (ESI-TOFMS) to structural elucidation of the fragment ions formed from a range of natural and synthetic allelochemical derivatives. The extensive mass spectrometric characterisation of ten non-glucosylated benzoxazinone derivatives using this method is described here for the first time. The analytes include six naturally occurring 1,4-benzoxazin-3(4H)-one derivatives, including the hydroxamic acids DIMBOA [2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one] and DIBOA [2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one], lactams HBOA [2-hydroxy-2H-1,4-benzoxazin-3(4H)-one] and HMBOA [2-hydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one], benzoxazolinones BOA [benzoxazolin-2(3H)-one] and MBOA [6-methoxy-benzoxazolin-2(3H)-one] and four synthetic variations, 2'H-DIBOA [4-hydroxy-2H-1,4-benzoxazin-3(4H)-one], 2'OMe-DIBOA [2-methoxy-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one], 2'H-HBOA [2H-1,4-benzoxazin-3(4H)-one] and 2'OMe-HBOA [2-methoxy-2H-1,4-benzoxazin-3(4H)-one]. Assignments of the mass spectral fragments were aided by elemental composition calculation results, comparison of structural analogues and background literature, and acquired knowledge regarding feasible structures for the compounds. The influence of substituents on the chemical reactivity of the compounds with respect to the observed MS behaviour over varying nozzle potentials is addressed and, through comparison of the structural analogues, generic fragmentation patterns have also been identified.     

A new hydroquinone diglucoside from <Emphasis Type="Italic">Lysimachia fordiana</Emphasis>

A new hydroquinone diglucoside along with five known compounds was isolated from the whole plant of Lysimachia fordiana Oliv. The structure of the new compound was determined to be 2-heptyl-6-methoxy-1,4-hydroquinone-1,4-di-O--D-glucopyranoside (6). The five known compounds were identified as pentacosane (1), stigmasterol (2), 2-heptyl-6-methoxy-1,4-benzoquinone (3), palmitic acid (4), and rutin (5), respectively. This is the first report of the isolation of Lysimachia fordiana Oliv. in the family Primulaceae.Published in Khimiya Prirodnykh Soedinenii, No. 5, pp. 377–379, September–October, 2004.     

A new course of the Perkin cyclization of 2-(2-formyl-6-methoxyphenoxy)alkanoic acids. Synthesis of 2-alkyl-7-methoxy-5-nitrobenzo[b]furans

2-Alkyl-7-methoxy-5-nitrobenzo[b]furan, 2-alkyl-9-methoxy-7-nitro-3-oxo-2,3-dihydro-5H-benzo[e][1,4]-dioxepin-5-yl acetate and 2-alkyl-5-hydroxy-9-methoxy-7-nitro-5H-benzo[e][1,4]-dioxepin-3-one were formed as a result of the cyclization of 2-(2-formyl-6-methoxy-4-nitrophenoxy)alkanoic acids under classical Perkin reaction conditions. The products were characterized by spectroscopic methods and the mechanism of the cyclization is discussed.     

Mercuric ion-catalyzed hydration of derivatives of 1,4-dichloro-2-butyne. Hydration of 1-aryloxy-4-arylthio-2-butynes, 1,4-bis(arylthio)-2-butynes,and 1,4-bis(arylsulfonyl)-1-butynes

The mercuric ion-catalyzed hydration of 1,4-bis(arylthio)-2-butynes and 1-aryloxy-4-arylthio-2-butynes was studied. The 1,4-bis(arylsulfonyl)-2-butynes afforded 1,4-bis(arylsulfonyl)-2-butanones (7). The 1,4-bis(arylthio)-2-butynes afforded a variety of products in acetic acid among which were: 1,4-bis(arylthiomethyl)vinyl acetate ( 18 ); 1,4-bis(arylthio)-2-butanone ( 15 ); 1-(arylthio)-3-buten-2-one ( 16 ); and 1-(arylthio)-4-acetoxy-2-butanone ( 17 ). Ketone 15 eliminates arylthiol in an acidic medium yielding 16 which undergoes Michael addition of solvent to give 17. Treatment of 7 with base in the presence of a nucleophile (ArSH) analogously leads to elimination of arylsulfinic acid, followed by Michael addition of arylthiol. Hydration of 5 in methanol cleanly gave 1-(arylthio)-4-methoxy-2-butanones ( 19 ). In contrast, 1-aryloxy-4-arylthio-24)utynes afforded chromenes ( 8 ) by intramolecular cyclization. No thiochromenes were formed in any of the examples investigated.     

Influence of chirality of the preceding acyl moiety on the cis/trans ratio of the proline peptide bond

We report that the cis/trans ratio of the proline peptide bond can be strongly influenced by the chirality of the acyl residue preceding proline. Acyl moieties derived from (2S)-2,6-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid (8) and (2R)-3-methoxy-2-methyl-2-(4-methyl-2-nitrophenoxy)-3-oxopropanoic acid (5) in acyl-Pro molecules influence isomerization of the proline peptide bond constraining the omega dihedral angle to the trans orientation. Structures of benzyl (2S)-1-([(2S)-2,6-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl)-2-pyrrolidinecarboxylate (3) derived from 2D (1)H NMR conformational analysis and crystallographic data exhibit only the trans conformation of proline peptide bond. On the other hand the diastereomer 4, which contains an (R) acyl moiety, exhibits two sets of signals in (1)H NMR spectra. The signals were assigned to trans (72%) and cis (28%) conformers. Crystallographic analysis of 4 showed that only the cis conformation is present in the crystalline state. The (1)H NMR chemical shift pattern of three sets of signals observed in 2 was observed also in benzyl (2S)-1-[(2R/S)-3-methoxy-2-methyl-2-(4-methyl-2-nitrophenoxy)-3-oxopropanoyl]-2-pyrrolidinecarboxylate. (R)-Carboxylic acid 5, after coupling with (S)-ProOBn, yielded benzyl (2S)-1-[(2R)-3-methoxy-2-methyl-2-(4-methyl-2-nitrophenoxy)-3-oxopropanoyl]-2-pyrrolidinecarboxylate (6), which in DMSO-d(6) exhibited only the trans conformation of the proline peptide bond. These results suggest that in these particular cases acyl-Pro peptide bond isomerization is strongly influenced by the stereochemistry of the acyl residue preceding proline. (2S)-2,6-Dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid (8) and (2R)-3-methoxy-2-methyl-2-(4-methyl-2-nitrophenoxy)-3-oxopropanoic acid (5) are promising chiral peptidomimetic building blocks that can be used as acyl moieties to force the proline peptide bond into the trans conformation in a variety of acyl-Pro molecules.     

Palladium (II) Assisted Preparation of Methoxyarylbenzoquinones

The reaction of 2-methoxy-1,4-benzoquinone with methoxyphenolic derivative compounds obtained from wood tar constituents, assisted by palladium (II) acetate in acetic acid, allowed the preparation of five novel methoxyaryl-substituted 1,4-benzoquinones, as well as four structural isomer mixtures.     

Lewis acid-directed cyclocondensation of piperidone enol ethers with 2-methoxy-4-(N-phenylsulfonyl)-1,4-benzoquinoneimine: a new regioselective synthesis of oxygenated carbolines

Lewis acid-directed cyclocondensations of piperidone enol ethers with 2-methoxy-4-(N-phenylsulfonyl)-1,4-benzoquinoneimine are reported. Benzofurans are obtained with BF3.OEt2 as a promoter, whereas use of excess amounts of TiCl4:Ti(OiPr)4 leads to tetrahydrocarbolines. The latter reactions provide expedient routes to oxygen-substituted tetrahydrocarbolines and carbolines. As applications of this new methodology, the preparations of 1-[3-(dimethylamino)propyl]amino-7-methoxy- and 1-[3-(dimethylamino)propyl]amino-7,8-dimethoxy-5H-pyrido[4,3-b]indoles are described.     

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.     

Unusual course of a type II photoreaction

The type II photoreaction of 1-acetyl-2-ethylidene-1-methoxycyclohexane (1) affords 2-ethylidene-1-methoxy-6-methylbicyclo[3.1.1]heptan-6-ol (2) as a result from ring closure of the least stable 1,4-biradical.     

Control of electron demand in the cycloadditions of 2(H)-1,4-oxazin-2-ones

3-Methoxy-5-chloro-6-methyl-2(H)-1,4-oxazin-2-one 4, 3-methoxy-5-chloro-6-phenyl-2(H)-1,4-oxazin-2-one 5, 3-phenylsulfenyl-5-chloro-6-methyl-2(H)-1,4-oxazin-2-one 6, and 3-phenylsulfenyl-5-chloro-6-phenyl-2(H)-1,4-oxazin-2-one 7, are ambident dienes and undergo Diels-Alder cycloadditions with electron neutral, rich and deficient dienophiles.     

Nontrivial intramolecular interaction in ozonation of dimethyl ester of endo,cis-bicyclo[2,2,1]hept-5-en-2,3-dicarbonic acid in diethyl ether

The formation of the product of intramolecular interaction of a zwitterion and a methoxycarbonyl group was observed in the process of ozonating dimethyl ester of endo,cis-bicyclo [2,2,1]hept-5-en-2,3-dicarbonic acid in diethyl ether. The structure of racemic endo,cis-4-methoxy-5-methoxycarbonyl-6-formyl-1,4-epoxy-2,3-dioxacyclopenta[2,3-δ] cyclohexane was established by an X-ray structure analysis.