Ring transformation of 3-halo-4-methoxycoumarins into pyrazoles with hydrazines

3-Chloro- and 3-bromo-4-methoxycoumarins 1a,b were readily transformed into 4-halo-5-(2-hydroxyphenyl)-3-oxo-2,3-dihydropyrazoles 2a,b with hydrazines. In the reaction of 1a,b with excess hydrazine and phenylhydrazine in boiling ethanol, unexpected 4-hydrazono-3-(2-hydroxyphenyl)-2-pyrazolin-5-ones 3 , 5 were obtained. The structure of 3 was determined by X-ray diffraction analysis.     

A Novel Route to the Synthesis of 3-Pyridine Carboxaldehydes by Vilsmeier Reagent

2-Chloro-5-aryl-3-pyridine carboxaldehydes are obtained by Vilsmeier reaction of 4-aryl-3-buten-2-one oxime. The suspected intermediate N-(2-arylethenyl)acetamides also give the same 2-chloro-5-aryl-3-pyridine carboxaldehydes under identical reaction condition.     

BCL-2选择性抑制剂——ABT-199的合成工艺改进

以3,3-二甲基环己酮(2)为原料,经5步反应制得中间体1-氯-4-［2-(氯甲基)-5,5-二甲基环己基-1-烯］苯（5）;以5-溴-7-氮杂吲哚为原料,经3步反应制得制得5-羟基-1-三异丙基硅基-7-氮杂吲哚（8）; 8与4-［3-氟-4-(甲氧基羰基)苯基］哌嗪-1-甲酸叔丁酯（9）经取代反应制得4-｛3-［(7-氮杂吲哚)氧］-4-(甲氧基羰基)苯基｝哌嗪-1-甲酸叔丁酯（10）;10脱保护后与5进行S_N2取代反应,所得中间体与3-硝基-4-｛［（四氢-2H-吡喃-4-基)甲基］氨基｝苯磺酰胺经缩合反应合成了BCL-2选择性抑制剂ABT-199,总收率28.4%,其结构经¹H NMR和ESI-MS确证。     

A three-component,intramolecular Ugi reaction toward unique indoloketopiperazines

2-(3-Chloro-2-formyl-1H-indol-1-yl) acetic acid, as a bifunctional formyl-acid, is prepared in three steps. This compound undergoes a one-pot, four-center, three-component Ugi reaction with primary amines and alkyl isocyanides. A series of novel substituted indoloketopiperazine derivatives are obtained in moderate to high yields.     

The first nonthiolic, odorless 1,3-propanedithiol equivalent and its application in thioacetalization

2-[2-Chloro-1-(1-chlorovinyl)allylidene]-1,3-dithiane 1 was synthesized by the chlorination of 3-(1,3)-dithianylidenepentane-2,4-dione 2 using the Vilsmeier-Haack reagent in 99% yield. As a novel nonthiolic, odorless 1,3-propanedithiol equivalent, 1 was investigated in the thioacetalization reaction. Various types of aldehydes and ketones 3 were converted to the corresponding dithianes 4 in the presence of 1 in high yields (79-97%). Moreover, 1 exhibited obvious chemoselectivity between aldehyde and ketone in this thioacetalization reaction. A mechanism for this thioacetalization reaction is proposed.     

A convenient preparation of 2-fluoro-3-alkoxy-1,3-butadienes

[reaction: see text] 1-Chloro-1-fluoro-2-methoxy-2-methylcyclopropane eliminates HCl on heating in quinoline solution above 50 degrees C to give 2-fluoro-3-methoxy-1,3-butadiene in high yield. If an alcohol is added to the reaction then a 2-fluoro-3-alkoxy-1,3-butadiene is obtained in high yield. The dienes give smooth 4 + 2 cycloaddition reactions.     

Etude Stéréochimique par RMN 1H de Tetrahydropyrannes β-Chlorés α-Substitués

The ¹H NMR study of 2-alkyl-3-chlorotetrahydropyrans, obtained by reaction of Grignard reagents with a mixture of cis/trans-2,3-dichlorotetrahydropyrans, shows cis/trans configuration of two isomers in which the alkyl substituents are exclusively in the equatorial position. 3-Chloro-2-phenyltetrahydropyran exists in trans (eq-eq) configuration only. The ¹H NMR study of cis/trans 2-alkoxy (or aryloxy)-3-chlorotetrahydropyrans, obtained by reaction of alcohols or phenol with 2,3-dichlorotetrahydropyrans, shows the axial position of the alkoxy (or aryloxy) substituent.     

Ringschlüsse an Chinonylmethanfarbstoffen und analogen Merocyaninen. 2. Mitteilung. Dihydronaphthophenazinone; Beeinflussung der Löslichkeitseigenschaften durch Substitution,Isolierung und Charakterisierung einer Zwischenstufe des Ringschlusses

Cyclization Reactions of Quinonylmethane Dyes and Analogous Merocyanines. 2. Communication: Dihydro-oxo-naphto-phenazines. Correlation of Solubility and Substitution. Isolation and Characterization of an Intermediate Compound An intermediate compound of the cyclization reaction of 2-chloro-3-(1-cyclohexyl-3-methyl-1,2-dihydroquinoxalin-2-ylidenmethyl)-naphthoquinone was isolated and characterized by spectroscopic methods. 6-Chloro-8-cyclohexyl-5,8-dihydronaphtho[1,2-b]phenazinone was obtained as the final product of this reaction. Several more dihydronaphtho[1,2-b]phenazinone dyes were synthesized. The relationship of substitution and solubility of the dyes is discussed. The visible and ¹H-NMR. and some mass spectra of the dyes are given.     

Synthesis of macroheterocyclic compounds on the basis of 3-chloro-2-hydrazinoquinoxaline

2-Amino-1-[(3-chloro-2-quinoxalinyl)azo]naphthalene was obtained by oxidative coupling of 3-chloro-2-hydrazinoquinoxaline with 2-aminonaphthalenesulfonic acid; cross self-cyclization of the product was used to synthesize macrocyclic compounds, viz., [1,2,5,8,9,12]hexaazacyclotetradecene derivatives. 4-[(3-Chloro-2-quinoxalinyl)azo]-5-chloro-3-methyl-1-phenylpyrazole was obtained by the reaction of the 4-(3-chloro-2-quinoxalinyl)hydrazone of 2,4-dihydro-5-methyl-2-phenyl-3H-pyrazole-3,4-dione with POCl₃. Reaction of this product with 2,2-diaminoazobenzene under standard conditions gave [1,2,5,8,9,12]-hexaazacyclotetradecene derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 546–551, April, 1981.     

Studies on pyrazines. 31 Alkylation of chloropyrazine N-oxides by nickel-catalyzed cross-coupling reaction with dialkylzincs

3-Chloro-2,5-dimethylpyrazine 1-oxide underwent cross-coupling with dialkylzinc reagents forming 3-alkyl-2,5-dimethylpyrazine 1-oxides. The reaction was realized by catalytic 1,3-bis(diphenylphosphino)-propane nickel(II) chloride and the optimum results were examined.     

氯雷他定的合成

以N-甲基-4-哌啶酮和8-氯-10,11-二氢-4-氮杂-5H-二苯并[a,d]-5-环庚酮为原料,经McMurry反应得到8-氯-6,11-二氢-11-(1-甲基-4-哌啶烯基)-5H-苯并[5,6]庚环[1,2-b]吡啶,收率为83.9%,最后与氯甲酸乙酯反应得到氯雷他定,总收率为35.7%。对McMurry反应过程中产生的副产物3、4进行了分离、表征。     

Study of the Products from Reaction of 1(2)-Aminoanthraquinones with 1-Chloro-2,3-Epoxypropane

1(2)-(3-Chloro-2-hydroxypropylamino)anthraquinones were synthesized by the reaction of 1(2)-aminoanthraquinones with 1-chloro-2,3-epoxypropane and were then subjected to various transformations.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 505–516, April, 2005.     

2′-Deoxyisoguanosine and Base-Modified Analogues: Chemical and Photochemical Synthesis

The synthesis of 2′-deoxyisoguanosine ( 2 ), and the pyrrolo[2,3-d]pyrimidine and pyrazolo[3,4-d]pyrimidine 2′-deoxyribonucleosides 3 and 4 is described. Condensation of the imidazole precursor 5 with benzoyl isocyanate followed by reaction with ammonia gave 2 . Its N(7) regioisomer was obtained from 6 . Compound 2 was also prepared by the photochemically induced conversion of 2-Chloro- and 2-bromopurine 2′-deoxyribofuranosides 9a and 10 , respectively, in aqueous solution, The photo reaction was further used for the synthesis of the compounds 3 and 4 starting with the amino-chloro-2′-deoxynucleosides 9b and 9c , respectively.     

Reactions involving fluoride ion Part XIII. Reactions of perfluoro-4-vinylpyridine

1-Chloro-1-(2′,3′,5′,6′-tetrafluoropyridyl)tetrafluoroethane, obtained by reaction of chlorotrifluoroethylene with pentafluoropyridine in the presence of caesium fluoride, was dehalogenated over iron at 310°, giving perfluoro-4-vinylpyridine (IV). Reactions of (IV) have been surveyed; nucleophilic attack occurs at both the ring and the difluoromethylene group using MeO^- but with PhO^-, selective attack at the difluoromethylene group occurred. A dimer is produced by reaction of (IV) with CsF and the intermediate carbanion was trapped with tetrafluoropyridazine. Thermal cyclodimerisation of (IV) gave a single isomer whose structure was established by n.m.r. and by defluorination to a cyclobutene. Cyclobutanes were formed in thermal cycloaddition reactions with chlorotrifluoroethylene and with hexafluoropropene. Photochemical reaction of (IV) with hexafluoroacetone gave an oxetane.     

Reaction of 3-chloroallyltrimethylsilane with acid chloride and exploitation of a new regioselective synthesis of αβ-unsaturated epoxide

α-Chloro-βγ-unsaturated ketone (2) was synthesized from the reaction of 3-chloroallyltrimethylsilane (1) with acid chloride. The ketone was converted into αβ-unsaturated epoxide (3) regioselectively in good yield via reduction with NaBH₄ or LiAlH₄ followed by treatment with NaOH. Treatment with methyl lithium instead of reduction gave homologous epoxide (5).     

Cascade Transformations of (2,2-Diaryl-3,3-dichloroaziridin-1-yl)acetates

Esters of (2,2-diaryl-3,3-dichloroaziridin-1-yl)acetic acid prepared from glycine derivatives under alkylation conditions afford esters of 2-[N-alkyl-N-(2,2-diaryl-1-cyanovinyl)amino]-3,3-diarylacrylic acid in 20-40% yield. The reaction resulting in these compounds proceeds through a cascade of 3-chloro-2-azadiene and ylide intermediates. 3-Chloro-2-azadienes originating from (2,2-diaryl-3,3-dichloroaziridin-1-yl)acetates react with primary and secondary amines at the carbon atom of imine group providing ketenimines which undergo ketenimine-nitrile rearrangement or fragmentation. The other bases (KOH, MeONa, DBU) effect dehydrochlorination of the mentioned 3-chloro-2-azadienes giving nitrile-ylides which are trapped by nucleophilic reagents. The 3-chloro-2-azadiene obtained from methyl (2,2-diaryl-3,3-dichloroaziridin-1-yl)acetate and DBU was relatively stable and was isolated as an individual compound. (2,2-diaryl-3,3-dichloroaziridin-1-yl)propionates behave as nonfunctionalized dichloroaziridines.     

A tandem Finkelstein-rearrangement-elimination reaction: a straightforward synthetic route to allyl esters

Allyl esters can be obtained by a Finkelstein-rearrangement-elimination reaction of 2-chloro-1-(chloromethyl)ethyl esters induced by NaI. Sodium iodide can be used below equivalence using a reductive agent as sodium thiosulfate. High yields are obtained with most of the diverse esters studied. The method described avoids the use of allyl alcohol as a reagent. 2-Chloro-1-(chloromethyl)ethyl esters are prepared from glycerol, the main by-product of biodiesel industry. The effectiveness of iodine as reagent to hydrolyze allyl esters is also confirmed.     

1-Chloro-2-azapropenylium and 1-chloro-2,4-diazabutenylium salts. Intermediates for the synthesis of pyrido[1,2-a]-1,3,5-triazinium salts

1-Chloro-1,3-bis(dimethylamino)-3-phenyl-2-azaprop-2-en-1-ylium perchlorate obtained from the reaction of phosphorus oxychloride-N,N-dimethylbenzamide complex and dimethylcyanamide reacts with 2-amino-4-methylpyridine to yield 8-methyl-4-dimethylamino-2-phenylpyrido[1,2-a]-1,3,5-triazinium perchlorate ( 8 ). The structure is established by X-ray crystallography. Various suitably substituted pyridines react similarly to afford the corresponding pyrido[1,2-a]-1,3,5-triazinium salts. The intermediates obtained from several secondary amides give identical products when treated with the same pyridines. The limitations of this procedure are investigated.     

新型无卤硅-氮成炭剂的合成及其热稳定性

以三聚氯氰和γ-氨丙基三乙氧基硅烷为原料,经取代反应制得2-氯-4,6-二(3-三乙氧基硅烷-1-丙氨基)-1,3,5-三嗪(3); 3与二乙烯三胺(4)反应合成了一种新型的无卤高含硅量的成炭剂(5),其结构和性能经¹H NMR, FT-IR和TGA表征。考察了物料比、缚酸剂、反应时间、反应溶剂和反应温度对5收率的影响。实验结果表明:最佳反应条件为：甲苯为溶剂,三乙胺为缚酸剂, n(3): n(4)= 3.3 : 1,于100 ℃反应11 h,收率62.7%; 5的初始分解温度为197 ℃, 700 ℃时残炭为36.7%。     

1-Chloro-2,6-dinitro-4-perfluoroalkylthiobenzenes in the Synthesis of Heterocycles

1-Chloro-2,6-dinitro-4-perfluoroalkylthiobenzenes was obtained in first time by perfluoroalkylation of bis(4-chloro-3,5-dinitrophenyl)disulfide in the presence of xenon bisperfluoroalkylcarboxylates. At the interaction of these compounds with potassium ethylxanthogenate only substitution of chlorine atom occurred. The reaction with sodium N,N-dimethyldithiocarbamate leads to the nucleophilic substitution of nitro group with formation of 1,3-benzodithiol-2-one, but on action of ethyl thioglycolate the intramolecular condensation occurs with formation of benzothiazoles N-oxides.