Reaktion von 2-(N-Alkyl-p-hydroxyanilino)-1,4-benzochinonen Diazomethan. N-(Alkyl-p-hydroxyanilino)-4,7-indazolchinone und ihre isomeren N-Methylderivate

The reaction of N-alkyl-p-hydroxyanilinobenzoquinones1 a–d, its acetylderivatives1 ₁–c₁ and the methoxyderivative1 a₂ with diazomethan yields in dependence on the reaction-conditions the indazolquinones2 a–d, 2 a₁–c₁ or2a ₂, the1-methylindazolquinones3 a–d and3 ₁–c₁, and finally the methoxy-1-methylindazolquinones5 a–d. The 2-methyl-isomeres6 a–d are formed only in small amounts. Methylation of2 a with dimethylsulfate gives5 a and6 a in the ratio of appr 2 to 1. Acetylation of2 a–d with acetanhydride leads to the N–O-acetylderivatives, which are easily hydrolyzed to2 a₁–d₁ during work up;3 a d yields3 a₁–d₁. The structures are established by the described crossexperiments and by spectroscopy (UV/VIS, IR, NMR).

Herrn Prof. Dr.G. Zigeuner zum 60. Geburtstag gewidmet.     

Der Einfluß von Stickstoffsubstituenten bei der Synthese von 3-Methyl-1,4-Benzoxazinen

Starting from1 the azomethine2 is obtained. The intermediates4 a and4 b of this reaction sequence cause the high yields. Cyclization of theN-alkylderivatives4 d and8 b leads also to an azomethine, which is obtained as its salt11. Cyclization of theN-acetylderivative13 yields however the anamine14. The structures of the new products are established by chemical and spectroscopic methods.

Teile aus der DissertationW. Kropp, Universität Wien, 1977.     

Strukturelle Abwandlungen an partiell silylierten Kohlenhydraten mittels Triphenylphosphan-Azodicarbonsäureester, 5. Mitt.: Transformationen an Glykonolactonen

Reaction ofD-glucono-1,5-lactone1 with two equivalents oft-butyldimethylchlorosilane yields via a ringcontraction 2,6-bis-O-(t-BDMSi)-D-glucono-1,4-lactone2a as main product and a small amount of 5,6-bis-O-(t-BDMSi)-D-glucono-1,4-lactone2c. Under the same conditionsL-mannono-1,4-lactone3 is transformed to the derivatives 2,6-bis-O-(t-BDMSi)-L-mannono-1,4-lactone3a and 3,6-bis-O-(t-BDMSi)-L-mannono-1,4-lactone3c as the minor product. 2,6-bis-O-(t-BDMSi)-D-galactono-1,4-lactone4a and 2,6-bis-O-(t-BDMSi)-D-gulono-1,4-lactone5a are also prepared from the corresponding glyconolactones4 and5. Whereas the compounds2a, 2c, 4a and5a withAc ₂O-pyridine give the bisacetylderivatives2b, 2d, 4b and5b, 3c is converted by an accompanying migration of one silylgroup to the 5,6-bis-O-(t-BDMSi)-2,3-bis-O-acetyl-L-mannono-1,4-lactone3d. The gluconolactone derivative2a reacts easily withTPP/DEAD/HX to the 5-X-L-idono-1,4-lactone derivatives6a (X=N₃),6b (X=p-NO₂-C₆H₄COO) and6c (3-O-acetylderivative of6a). Treating6b with a second equivalentTPP/DEAD/HX leads to the unsaturated sugarlacton7b. Without an external nucleophile2a affords withTPP the mixture of 2,6-bis-O-(t-BDMSi)-3,5-carbonato-D-glucono-1,4-lactone2c, 3,5-anhydro-L-idono-1,4-lactone8 and 3,6-anhydro-D-glucono-1,4-lactone9. Analogous procedures applied to4a yield theL-altronolactonoderivatives10a, 10b and10c, the unsaturated sugarlactone11b on the one and the 3,5-carbonatogalactonolactone4c and the 2,6-bis-O-(t-BDMSi)-3-desoxy-5-ethoxycarbonyl-D-threo-hex-2-en-1,4-lactone12 on the other hand.Whereas the bis-silyletherderivative3a is transformed by the title system exclusively by an elimination process to13, the derivative5a affords withTPP/DEAD without any elimination the 3,6-anhydrosugar14. Partial desilylation of14 followed by acetylation gives the derivatives14a and14b.Structural elucidations were achieved by¹H-NMR-analysis. In some cases also CD-measurements allowed suitable correlations.

Mark, E., Zbiral, E., Brandstetter, H. H., 4. Mitt., Mh. Chem.111, 289 (1980).     

Synthesis of imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridones and imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridines as potential antibacterial agents

Abstract  New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug. Graphical abstract        

Synthetic studies in quest of Platonic hydrocarbon dodecahedrane

In pursuit of Platonic hydrocarbon dodecahedrane1, a retrosynthetic theme indicated in scheme 1, was formulated. The precursor tetraquinanedione synthon5 was first designed through a photo-thermal olefin metathesis approach. The tetraquinanedione 5 was further elaborated toexo, exo-tetraquinane diester15 through carbonyl homologation, oxidation, esterification sequence, scheme 5. Bis-cyclopentannulation ofexo,exo-diester15 by Greene methodology delivered a functionalised C₂₀-hexaquinane44, havingexo-annulated cyclopentane rings. Cyclopentane inversion was achieved by a set of reactions involving enone generation, double bond isomerisation and hydrogenation to give spheroidal (C_2v)-C₂₀-hexaquinanedione-diester47, the penultimate precursor of dodecahedrane 1. Several interesting transformations and rearrangements of polyquinanes are also described. IUPAC nomenclature: Undecacyclo[9.9.0.0^2,9.0^3,7.0^4,20.0^5,18.0^6,16.0^8,15.0^10,14.0^12,19.0^13,17]eicosane.     

水溶性稠杂环均三唑并噻二唑体系的合成及生物活性(I): 哌嗪取代衍生物

4-氨基-5-吡啶-4-基-均三唑硫醇(1)在复合催化剂DMAP和TBAB作用下与对卤代苯甲酸经环缩合反应以高收率得到中间体6-(5-氯-3-甲基-1-取代苯基-1H-吡唑-4-基)-3-吡啶-3-基-均三唑并[3,4-b][1,3,4]噻二唑(2a～2c), 接着苯环卤原子与取代哌嗪在聚乙二醇催化作用下发生亲核取代反应得到相应的哌嗪游离碱(3a～3c). 其中, 单取代哌嗪游离碱3a与含功能基的卤代物缩合得到功能基取代的哌嗪衍生物(4a～4g). 这些产生的游离碱与盐酸反应得到相应的水溶性盐酸盐. 所合成新化合物的结构经元素分析和光谱数据表征, 并评价了它们的体外抗菌活性及构效关系.     

Synthesis and Biological Activities of Novel 1,4-Bridged Bis-1,2,4-Triazoles,Bis-1,3,4-Thiadiazoles and Bis-1,3,4-Oxadiazoles

Abstract

The terephthalic acid hydrazide(1) reacted with phenyl/benzyl isothiocyanate2a,bto yield the corresponding bis-thiosemicarbazides4a,b,viaacid hydrolysis of the intermediate 3whereas cyclization of4gave the bis-1,2,4-triazoles 5,6and bis-1,3,4-thiadiazoles7,8. Similarly, compound 1reacted with phenyl isocyanate9to give the bis-semicarbazide10, which was cyclized to the bis-oxadiazole 11and/or bis-1,2,4-triazole12in POCl_ti3and NaOH respectively.     

2-[3-(Trifluoromethyl)phenyl]furo[3,2-b]pyrroles: synthesis and reactions

The synthesis and reactions of methyl 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole-5-carboxylate (1a) are described. Upon reaction with methyl iodide, benzyl chloride, or acetic anhydride, this compound gave N-substituted products 1b-d. By hydrolysis of compounds 1a-c, the corresponding acids 2a-c were formed, or by reaction with hydrazine-hydrate, the corresponding carbohydrazides 3a-c were formed. By heating 2-[3-(trifluoromethyl)phenly]-4H-furo[3,2-b]pyrrole-5-carboxylic acid (2a) in acetic anhydride, 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-b]pyrrole (4) was formed. By hydrolysis of 4, 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole (5a) was formed, and reactions with methyl iodide or benzyl chloride gave N-substituted products 5b-c. The reaction of 4 with dimethyl butynedioate gave substituted benzo[b]furan 6. Compound 3a reacted with triethyl orthoesters giving 7a-c, which afforded with phosphorus (V) sulphide the corresponding thiones 8a-c. The thiones 8a-c reacted with hydrazine hydrate to form hydrazine derivatives 9a-c. The reaction of triethyl orthoformiate with compounds 9a-c led to furo[2′,3′: 4,5]pyrrolo[1,2-d][1,2,4]triazolo[3,4-f][1,2,4]triazines 10a-c. Hydrazones 11a-c were formed from 3a-c and 5-[3-(trifluoromethyl)phenyl]furan-2-carboxaldehyde. The effect of microwave irradiation on some condensation reactions was compared with “classical” conditions. The results showed that microwave irradiation shortens the reaction time while affording comparable yields.     

焦脱镁叶绿酸甲酯的Vilsmeier反应合成δ-meso-甲酰乙烯基卟吩和苯并异细菌卟吩

From methyl pyropheophorbide-a (MPPa, 1), the vinyl group of methyl pyropheophorbide-a was converted into alkylcarbonyl group by Grignard reaction and oxidization to give chlorins 2, 3 and 5. The Vilsmeier reaction of nickel 3-substituent-3-devinylpyropheophorbide-a (6), which was prepared by the metallation with nickel acetate, with 3-dimethylamino-acrolein/phosphoryl chloride (3-DMA/POCl3) was carried out to give δ-meso-formylvinylpyropheophorbide-a (7) in good yield. The benzoisobacterichlorin (8) was obtained by the treatment of 7b with concentrated sulfuric acid.     

Stereochemie von Metallocenen, 43. Mitt.: Torsionsisomere Biphenyl-tricarbonylchrom-Komplexe: Darstellung,Konformationsanalyse und Kinetik der Interkonversion

Complexation of methyl 3-nitro-2-(o-tolyl)-benzoate (2, ano-trisubstituted biphenyl) with hexacarbonyl chromium gave the isomeric Cr(CO)₃ complexes3 and4 both existing as two torsional isomersa andb, as seen by nmr. For the main product3 the preferred conformations of the two torsional isomersa andb were deduced by the lanthanide induced shift (LIS) technique. The activation energy for the interconversion process could be determined from kinetic measurements and especially from¹H-nmr coalescence temperature of the methylsignals. The barrier of 91±1.5 kJ/mol (21.7±0.3 kcal/mol) in3 reflects the interaction of theo-H-atom of the benzene ring passing the Cr(CO)₃ moiety of the benchrotrene ring during the interconversion.A partial optical resolution of3 was achieved by asymmetric reduction with a chiral lithium-aluminium hydride yielding (+)-3 with [] _D ²⁰ +30° (benzene) and the levorotatory alcohol (–)-7.

42. Mitt.:K. Schlögl undR. Schölm, Mh. Chem.109, 1227 (1978).     

Synthetic study of hepoxilins

Total synthesis of trioxilin (10S,11S,12S)-B₃ was performed starting from a hepoxilin synthon, (2S,3S)-2,3-epoxyundec-5-yn-1-ol, available from the corresponding allylic alcohol by Sharpless enantiodirected epoxidation. The synthesis features stereoselective (7 ∶ 1)syn-addition of the acetylenide anion to the intermediate (2S,3S)-2,3-(isopropylidenedioxy)undec-5-yn-1-al and regioselective partial hydrogenation of a triacetylene trioxilin precursor, which allowed the preparation of 14,15-dehydro-(10S,11S,12S)-TrXB₃. For part 8, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 545–551, March, 2000.     

Synthesis of 3-methyl-coumarins, -thiacoumarins and -carbostyrils

Reaction of 3,6-dimethyl-4-phenyl-3,4-dihydrocoumarin5a with anhydrous aluminum chloride gave 3,6-dimethyl-coumarin (6a); likewise, 6-chloro-3-methyl-coumarin (6b) was obtained from5b. Substituted 3-methyl-thiacoumarins (8a,b and 3-methyl-carbostyrils (10a-e) were prepared from the reactions of the respectivea-methyl-cinnamoyl derivatives (7a,b and (9a-e), of thiophenols and anilines.     

Protoberberine ausReissert-Verbindungen, 5. Mitt.: Synthese des (±)-Bharatamins

Summary Alkylation of theReissert compound1 by methyl 2-bromomethylbenzoate (2) followed by spontaneous intramolecular cyclization affords dibenzo [a,g]quinolizinone4 which in turn can be reduced to benzyl ether5 by LiAlH₄/NaBH₄. Debenzylation of5 by ethanolic HCl furnishes the title compound6 in improved total yield.

     

三有机锡（4R）-3-[[（2S）-5-氧-2-吡咯烷基]羰基]-4-噻唑烷甲酸酯的合成、结构和体外抗癌活性

利用三有机锡氢氧化物和手性配体（4R）-3-[[（2S）-5-氧-2-吡咯烷基]羰基]-4-噻唑烷甲酸（HL）反应合成了3个三有机锡（4R）-3-[[（2S）-5-氧-2-吡咯烷基]羰基]-4-噻唑烷甲酸酯R₃SnL[1,R=c-C₆H₁₁（a）,C₆H₅（b）,C₆H₅C（CH₃）₂CH₂（c）],通过元素分析、IR、¹H NMR和X-射线单晶衍射表征了其结构。化合物1a属正交晶系,P2₁2₁2₁空间群;化合物1b属单斜晶系,P2₁空间群。二者均为由羧基氧和内酰胺羰基氧桥联配位形成的右螺旋链状有机锡配位聚合物,锡原子具有五配位[SnC₃O₂]畸变三角双锥构型。化合物1a和1b对体外2种人癌细胞Colo205和Bcap37增殖均有强的抑制作用,其活性为1b >1a。     

Are all charge-repulsed carbocations really unstable? Dramatic difference in reactivities of benzyl- and p -methoxybenzyl halides in benzene

Two distinct reaction mechanisms are proposed for the reactions of1,5 and6 with nucleophiles as against those of11,12 and16. The former set undergoes the reactions through carbocation type intermediates2 and3 as efficiently as the stable carbocation4 does, even under similar and very mild conditions. The compounds from the latter group do not form the carbocations under the same conditions and undergo only direct substitution by strong nucleophiles.     

Crystal structure and vibrational spectra of pyridine-2,6-dithio-carbomethylamide

The crystal structure of Pyridine-2,6-dithio-carbomethylamide (PDTA) is described: C₉H₁₁N₃S₂, monoclinic, P2₁/c,Z=4,a=6.000 (1) Å,b=8.840 (1) Å,c=21.452 (1) Å, =105.47 (1)^o,d _x=1.47 gcm^–3. The structure was solved with direct methods and refined to a conventionalR-factor of 0.047. The molecule is nearly planar in the crystal. There are possibly weak intramolecular H-bonds between the two amide nitrogens and the pyridine nitrogen and intermolecular H-bonds between two amide nitrogens and one thioamide sulfur atom. The IR andRaman spectra ofPDTA and deuteratedPDTA are discussed.

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Kristallstruktur und Schwingungsspektren von Pyridin-2,6-dithiocarbomethylamid

Zusammenfassung Die Kristallstruktur von Pyridin-2,6-dithiocarbomethylamid (PDTA) wurde bestimmt: C₉H₁₁N₃S₂, monoklin, P2₁/c,Z=4,a=6,000 (1) Å,b=8,840 (1) Å,c=21,452 (1) Å, =105,47 (1)^o,d _x=1,47 gcm^–3. Das Phasenproblem wurde mittels direkter Methoden gelöst und die Struktur bis zu einemR-Faktor vonR=0,047 verfeinert. Das Molekül ist im Kristall nahezu planar. Das Vorliegen schwacher intramolekularer Wasserstoffbrücken zwischen den beiden Thioamid-Stickstoffatomen und dem Pyridinstickstoff sowie intermolekularer Wasserstoffbrücken zwischen Thioamid-Stickstoff- und Thioamid-Schwefelatomen wird postuliert. IR- undRaman-Spektren vonPDTA und deuteriertemPDTA werden diskutiert.

     

Synthesis,structure and isomerism of “three-bridge” exo-nido-osmacarborane clusters

The reaction of OsCl₂(PPh₃)₃ with [nido-7-R¹-8-R²-C₂B₉H₁₀]K⁺ produced a series of new exo-nido-osmacarborane complexes exo-nido-5,6,10-[Cl(Ph₃P)₂Os]-5,6,10-(-H)₃-10-H-7-R¹-8-R²-7,8-C₂B₉H₆ (1: R¹ = R² = H; 2: R¹ = R² = Me; 3: R¹ = R² = PhCH₂; 4: R¹ + R² = 1,2-C₆H₄(CH₂)₂; 5: R¹ = H, R² = Me) in which the osmium-containing group is linked to the nido-carborane ligand through three two-electron three-center bonds. Compounds 1—5 are formed as mixtures of symmetric (a) and asymmetric (b) isomers; pure symmetric isomers 2a and 4a were isolated by fractional crystallization, and the mixture of isomers 3a, was quantitatively separated into individual compounds 3a and 3b by column chromatography on silica gel. Detailed analysis of the ³¹P{¹H}, ¹H, ¹¹B NMR spectra of 1a,b—5a,b and 2D ¹H-¹H{¹¹B} and ¹¹B{¹H}-¹¹B{¹H} NMR spectra of 3a and 3b was performed. The structures of isomers 2a and 4a were confirmed by an X-ray diffraction study. According to the NMR and X-ray diffraction data, the isomerism of exo-nido-complexes 1a,b—5a,b is actually the cis—trans-isomerism of ligand arrangement in the octahedral coordination of the Os atom.     

Copper and palladium complexes with N-heterocyclic carbene ligands functionalised with carboxylate groups

The new imidazolium salts functionalised with the trimethylsilyl ester group 1a–c, were easily obtained by quaternisation of alkyl- or aryl-imidazoles with trimethylsilyl bromoacetate. Salt 1a was isolated and fully characterised. It reacted with mesityl copper (Cu₅Mes₅) under trimethylsilyl abstraction to form the complex 2. Methanolysis of 1a–c gave good yields of the carboxylic acid functionalised imidazolium salts 3a–c. Deprotonation of the latter in liquid ammonia led to the zwitterionic imidazolium carboxylates 4a–c. Reaction of 4a with (Cu₅Mes₅) gave solutions from which the insoluble polymeric 5a crystallised slowly. Generation of the carboxylate-functionalised NHC in situ followed by reaction with Pd(OOCCH₃)₂ gave the new complex 6a in which the NHC-carboxylate ligand is chelate bidentate.     

Zur Umsetzung von 8a-Methoxy-3,4-dihydro-2H-1,4-benzoxazin-6(8aH)-onen mit Diazoalkanen, 2. Mitt.

Summary 8a-Methoxy-3,4-dihydro-2H-1,4-benzoxazin-6(8aH)-ones2 undergo regio- and stereospecific 1,3-dipolar cycloaddition reactions with diazomethane or diazoethane to yield 3,4,6a,9,9a,9b-hexahydro-pyrazolo[3,4-h][1,4]benzoxazin-6(2H)-ones3, which slowly isomerize in solution to give the 3,4,8,9,9a,9b-hexahydro-pyrazolo[3,4-h][1,4]benzoxazin-6(2H)-ones5. The carbon of the diazoalkane dipole is attached to carbon C-8 of the benzoxazinone. The structures of the obtained products were determined by¹H- and¹³C-NMR spectroscopy. An X-ray crystal structure analysis of3 a was carried out at room temperature:C₁₁H₁₅N₃O₃,M _r =237.26, orthorhombic, Pc2₁n,a=9.173 (5),b=9.133 (4),c=13.281 (6),V=1112.6 (9) ų,Z=4,d _x =1.416 g/cm^–3, =0.93 cm^–1,R=4.33%,R _w =3.95% (919 observations, 168 parameters).

Herrn Prof. Dr. W. Fleischhacker zum 60. Geburtstag gewidmet