Synthese und Reaktionsverhalten von 3-(Bis(alkylthio)methylen)-3H-isobenzofuran-1-on-und 2-(Bis(alkylthio)methylen)-3(2H)-benzofuranon-Derivaten

Summary 3(Bis(alkylthio)methylene)-3H-isobenzofuran-1-ones2a–e and 2-(bis(alkylthio)methylene)-3(2H)-benzofuranone derivatives4a–c are obtained by reaction of phthalides1a–d or 3(2H)-benzofuranone (coumaranone3), respectively, with carbon disulfide under basic conditions followed by alkylation. The reaction behaviour of the new compounds2 and4 is investigated. 2-((2-Dimethylthio-1-oxo)ethyl)benzoic acid N,N-dimethylamide (7a) and 2-((2-dimethylthio-1-oxo)ethyl)-benzoic acid 2-methylpiperidide (7b) are surprisingly formed instead of the methylthio substitution products by treatment of2a with the corresponding amine in the presence of aluminum chloride.

Herrn Professor Dr. Dr. h. c.Waldemar Adam zum 60. Geburtstag gewidmet     

Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters

Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO₂ in 6% H₂SO₄ in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K₂CO₃ and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.     

Preparation and Structure of (E)-1-(3′-Hydroxy-2-Furanyl)-3-(3″-Hydroxy-4″-Methoxyphenyl)-2-Propen-1-One

Abstract

A facile procedure is presented for the synthesis of (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2- propen-1-one (6). Galactosylisomaltol (1) was condensed with isovanillin (2) under strong alkaline conditions at 25 [ddot]C to form (E)-1-(3′-O-β-D-galactopyranosyloxy-2′-furanyl)-3-(3″- hydroxy-4″-methoxyphenyl)-2-propen-1-one (4). (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2-propen-1-one (6) was obtained by acid hydrolysis of 4 in a 53.9% yield. This hetero-cyclic 2-propen-1-one was characterized on the basis of spectral data (IR and ¹H NMR), physicochemical properties, and conversion to a mono-O-acetyl derivative.     

Synthesis and characterization of copper(II) complexes with 3-methylpicolinic acid. Crystal and molecular structure of bis (3-methylpicolinato- N,O )(4-picoline)copper(II)

Copper(II) complexes of 3-methylpicolinic acid (3-MepicH), namely [Cu(3-Mepic)₂] · 2H₂O (1) and [Cu(3-Mepic)₂(4-pic)] (2) were prepared and characterized by IR spectroscopy and thermal analysis (TGA/DTA). Crystal structure for 2 was determined by X-ray crystal structure analysis. 1 was prepared by reaction of copper(II) sulfate pentahydrate and 3-methylpicolinic acid in aqueous solution, while 2 was prepared by recrystallization of 1 from 4-picoline solution. Structure analysis revealed square-pyramidal copper(II) coordination and N,O-chelating mode of 3-methylpicolinic acid in 2. Copper(II) is coordinated by two 3-Mepic ligands in the basal plane of a square pyramid and by 4-picoline in the apical position. Crystal packing of 2 is dominated by weak intermolecular C–H ··· O hydrogen bonds and π ··· π stacking interactions forming a complex three-dimensional supramolecular architecture.     

Cadmium(II), manganese(II) and zinc(II) compounds

Three new compounds, [Cd(μ ₃ -Hpdh)(μ₂-Cl)] _n (1), Mn(Hpdh)₂(H₂O)₂ (2) and Zn(Hpdh)₂ (H₂O)₂ (3) (H₂pdh =?pyridine-2,3-dicarbo-2,3-hydrazide), have been synthesized and characterized by elemental analysis, IR spectra, TG and single-crystal X-ray diffraction. Under hydrothermal conditions, H₂pdh is generated by an in situ acylation of H₂pda (H₂pda =?pyridine-2,3-dicarboxylic acid) with hydrazine hydrate. Complex 1 features a 2D layer structure constructed by a dinuclear Cd(II) building block. In complexes 2 and 3, hydrogen bonding interactions connect mononuclear structures into 3D supramolecular frameworks.     

Two new triterpenoids from the seeds of blackberry (Rubus fructicosus)

Two new ursane-type triterpenoids (1, 2) attached to isopropylidenedioxy group were isolated from the seeds of blackberry (Rubus fructicosus L., Rosaceae) along with two known ursane-type triterpenoids, 2,3-O-isopropylidenyl-2α,3α,19α-trihydroxyurs-12-en-28-oic acid (3) and 1β-hydroxyeuscaphic acid (4). The chemical structures of 1 and 2 were determined to be 2,3-O-isopropylidene-1β,2β,3β,19α-tetrahydroxyurs-12-en-28-oic acid and 1,2-O-isopropylidene-1β,2α,3α,19α-tetrahydroxyurs-12-en-28-oic acid, respectively, based on spectroscopic data. Additionally, their cytotoxic activity towards HL-60 human leukaemia cells was evaluated. Among them, 3 demonstrated a clear cytotoxic activity with 72.8 μM of IC₅₀ value.     

Diels-Alder reaction of fulvenes with N-(3,5-dichlorophenyl)-maleimide

Summary N-(3,5-Dichlorophenyl)-maleimide reacts smoothly with a variety of substituted fulvenes (1) to give onlyendo adducts (3) independent of the nature of fulvene substituent,Lewis acid catalyst, and reaction solvent and temperature. The structure of theDiels-Alder adduct3f was determined by X-ray crystallography. Semi-empirical quantum methods (AM1) were used to rationalize theendo stereoselectivity.Dedicated to Professor Fritz Sauter on the occasion of his 65^th birthday     

Cu(II)/Cd(II) coordination polymers based on polycarboxylate and 2-(2-pyridyl)benzimidazole

Three polycarboxylate coordination polymers containing 2-(2-pyridyl)benzimidazole as co-ligand, [Cu(Bdc)(2-PyBIm)] _n (1), [Cu(HBtc)(2-PyBIm)] _n (2) and [Cd₂(HBtc)₂(2-PyBIm)₂] _n ·; nH₂O (3) (H₂Bdc?=?1,4-benzenedicarboxylic acid; H₃Btc?=?1,3,5-benzenetricarboxylic acid), have been synthesized and characterized by elemental analyses, IR spectra, TG-DSC and X-ray structural analyses. Complex 1 is a one-dimensional zigzag chain in which the Cu(II) is cis six-coordinated by two chelating carboxyl groups and a 2-PyBIm ligand. Complex 2 is a two-dimensional (4, 4) network in which H₃Btc is partially deprotonated. Complex 3 has a three-dimensional framework in which one Cd(II) is six-coordinate and the other is seven-coordinate. All 2-PyBIm groups are neutral, chelating, bidentate ligands in 1–3. These complexes are quite thermally stable. The luminescence of 3 has also been investigated.     

Enantioselective Synthesis of Ipsenol and Ipsdienol Using a (2-Bromoallyl)borane Derivative

(S)-(-)-Ipsenol (2b) and (S)-(+)-ipsdienol (4b), a major component of the sex pheromone of the bark beetle, and their enantiomers (3b and 5b) were prepared enantioselectively using tartrate esters of (2-bromoallyl)boronic acid in the key step.

     

Pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazine-7,9(6H8H)-diones

Some 5H-pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazine-7,9-(6H,8H)-diones (4 a–d) have been synthesised by the condensation of 3-alkyl-4-amino-5-mercapto-(1,2,4)-triazoles (1 a–d) with 5-bromobarbituric acid (2a). Similarly some 9a-nitro-5H-pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazine-7,9(8H,9aH)-diones (5 a–d) have been obtained by the condensation of1 a–d with 5-bromo-5-nitrobarbituric acid (2b) and final cyclisation withPPA. The structures have been confirmed by PMR spectra and analytical results.

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Pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazin-7,9(6H,8H)-dione

Zusammenfassung Es wurden einige 5H-pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazin-7,9(6H,8H)-dione (4 a–d) mittels Kondensation von 3-Alkyl-4-amino-5-mercapto-(1,2,4)-triazolen (1 a–d) mit 5-Brombarbitursäure (2 a) dargestellt. Des weiteren wurden einige 9a-Nitro-5H-pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazin-7,9(8H,9aH)-dione (5 a–d) über die Kondensation von1 a–d mit 5-Brom-5-nitrobarbitursäure (2 b) und anschließender Cyclisierung mitPPA synthetisiert. Die angeführten Strukturen wurden mittels PMR-Spektren und analytischen Daten abgesichert.

     

Darstellung und Charakterisierung von Halogeno(diethyldithiocarbamato) (triethyl- und triphenylphosphin)palladium(II)-Komplexen

The Complexes [Pd(PEt ₃)₂ dtc]X (1) and Pd(PR ₃)Xdtc (2, 3) (dtc=S₂CNEt ₃;X=Cl, Br, I;R=Et, Ph) have been prepared. Conductivity, susceptibility, UV and IR measurements show that the cations [Pd(PEt ₃)₂ dtc]⁺ of1 and the complexes2, 3 have square-planar structure.

     

Natural product chemistry,Part 132: Synthesis and oxidative cyclisation of 1,3-dihydroxy-10-methyl-4-(3-methylbut-2-enyl)-9(10H)-acridinone (glycocitrine-II)

Summary Reaction of 1,3-dihydroxy-10-methyl-9(10H)-acridinone (1) and 1-bromo-3-methylbut-2-ene (mol. ratio 1:1) in tetrahydrofuran at 20°C in the presence of alumina gave prenylacidinones2 (glycocitrine-II) and8 and the diprenylacridinone9; with an excess of 1-bromo-3-methylbut-2-ene, the prenyldihydropyranoacridinones12 and13 were formed. Oxidation of glycocitrine-II (2) withm-chloroperbenzoic acid furnished the furanoacridinone5 and the pyranoacridinone6; dehydration of the latter compound gave noracronycine (10).(the late)     

Rauvolfianine,a new antimycobacterial glyceroglycolipid and other constituents from Rauvolfia caffra. Sond (Apocynaceae)

The chemical investigation of the extract of the dried leaves of Rauvolfia caffra (Sond) (synonym Rauvolfia macrophylla) (Apocynaceae) led to isolation of a new glycoside derivative, rauvolfianine (1) as well as six known compounds: oleanolic acid (2), sitosterol-3-O-β-D-glucopyranoside (3), betulinic acid (4), vellosimine (5), sarpagine (6) and D-fructofuranosyl-β-(2→1)-α-D-glucopyranoside (7). Compounds 1, 2, 3, 4 and 7 were evaluated for antitubercular activity. Compounds 1 and 2 were the most active (MIC = 7.8125 and 31.25 μg/mL) towards the Isoniazid resistant strain of Mycobacterium tuberculosis AC45. Their structures and relative stereochemistry were elucidated by spectroscopic methods.     

The preparation of 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-one and its rearrangement to 3-amino-2,4(1H,3H)-quinazolinedione

When anthranilic acid hydrazide is reacted with 1,1-carbonyldiimidazole inTHF 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-one (4) is formed. It can also be prepared from 1-o-aminobenzoyl-4,4-dimethylsemicarbazide which eliminates methylamine when boiled withDMF. On heating the 5-(2-aminophenyl)-1,3,4-oxiadiazole above its melting point it rearranges to 3-amino-2,4(1H,3H)-quinazolinedione (5).

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Die Darstellung von 5-(2-Aminophenyl)-1,3,4-oxadiazol-2(3H)-on und dessen Umlagerung in 3-Amino-2,4(1H,3H)-chinazolindion

Zusammenfassung Bei der Reaktion von Anthranilsäurehydrazid mit 1,1-Carbonyldiimidazol inTHF wird 5-(2-Aminophenyl)-1,3,4-oxadiazol-2(3H)-on (4) gebildet. Dieses kann auch aus 1-o-Aminobenzoyl-4,4-dimethylsemicarbazid dargestellt werden, welches beim Kochen mitDMF Methylamin eliminiert. Beim Erhitzen von 5-(2-Aminophenyl)-1,3,4-oxadiazol über seinen Schmelzpunkt tritt Umlagerung zu 3-Amino-2,4(1H,3H)-chinazolindion (5) ein.

     

A DIRECT LITHIATION ROUTE TO 2-ACYL-1-(PHENYLSULFONYL)INDOLES

ABSTRACT

2-Acyl-1-(phenylsulfonyl)indoles (3, 7–9) are prepared in 75–84% yield from 1-(phenylsulfonyl)indoles (1, 5) in one operation by treatment of the latter with s-butyllithium followed by inverse quenching of the C-2 lithioindoles with carboxylic acid anhydrides (6).     

New Synthetic Route to (1S)-4,5-Dimethoxy-1-[(methylamino)methyl] Benzocyclobutane,a Key Intermediate of Ivabradine

An efficient process for the preparation of (1S)-4,5-dimethoxy-1-[(methylamino)methyl] benzocyclobutane (S)-3 as ivabradine intermediate, which was obtained in 56% yield, is described. The salient feature of this process is the racemization of the undesired (1R)-4,5–dimethoxy-1,2-dihydrocyclobutabenzene-1-carboxylic acid (R)-12, and the overall yield of (S)-12 was improved to 70% by three resolutions of the racemized acid with R-(α)-phenylethanamine. The reduction of amide (S)-13 was achieved with NaBH₄-I₂ in refluxing tetrahydrofuran, giving the corresponding amine (S)-3 in 90% yield. The improved synthetic route described herein is cost-efficient, environmentally friendly and feasibile for scale-up production.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

The (E)/(Z)-ratio in the reaction of 5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines with bromine

Summary 3-Aryl-, 3-benzyl-, and 3H-5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines3a–h react with bromine in acetic acid solution to give mixtures of the respective 5-aroylmethylene (E) and (Z) diastereomeric derivatives5 and6. They contain more than 85% of the (E)-diastereomers along with some pure isomers. The intermediacy of the 5-bromo derivatives4 is proven and a plausible route of the reaction is presented. Structures of compounds3–6 are evidenced by analytical and spectral data.

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Das Verhältnis von (E)- und (Z)-Isomeren bei der Reaktion von 5-(2-Aryl-2-oxomethyl)-2-thioxo-4-oxo-1,3-thiazolidinen mit Brom

Zusammenfassung 3-Aryl-, 3-Benzyl- und 3H-5-(2-Aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidine3a–h reagieren mit Brom in essigsaurer Lösung zu Gemischen der entsprechenden diastereomeren 5-Arylmethylen-Derivate ((E) und (Z))5 und6. Sie enthalten mehr als 85% des (E)-Diastereomeren. Die intermediäre Natur der 5-Brom-Derivate4 wird bewiesen; ein Reaktionsweg wird vorgeschlagen. Die Strukturen der Verbindungen3–6 werden durch analytische und spektroskopische Daten abgesichert.

     

FORMATION EQUILIBRIA OF COPPER(II) TERNARY COMPLEXES WITH (S)-LEUCINEHYDROXAMIC ACID AND (R)- OR (S)-AMINO ACIDS IN AQUEOUS SOLUTION

Abstract

Solution equilibria of binary copper(II) complexes with (S)-leucinehydroxamic acid and of ternary complexes with (R)- or (S)-amino acids (valine, proline, phenylalanine, tryptophan) were studied by potentiometry and electronic spectrophotometry at T=25°C and I= 0.5moldm^?3 (KCl). The mixed species [CuLA] and [CuLH-^IA]^? (L^?=leucinehydroxamate, A^?= aminoacidate), do not present stereoselectivity, but are strongly stabilized with respect to their parent binary complexes. Possible structures of the ternary complexes are proposed.     

Darstellung und Charakterisierung von Halogeno(diethyldithiocarbamato) (triethylphosphin)-nickel(II)-Komplexen

The complexes [Ni(PEt ₃)₂ dtc]X (1) and Ni(PEt ₃)Xdtc (2) (dtc=S₂CNEt ₂,X=Cl, Br, I) have been prepared. As conductivity, susceptibility, UV and IR measurements show, the cations [Ni(PEt ₃)₂ dtc]⁺ of1 and the complexes2 at ambient temperature have square-planar structure. We suppose there might exist an equilibrium for2 between square-planar and tetrahedral configuration.

     

Molybdic Acid-Catalysed Isomerization of D-Ribulose and D-Xylulose to the Corresponding 2-C-(Hydroxymethyl)-D-Tetroses

ABSTRACT

2-C-(Hydroxymethyl)-D-erythrose (2) and 2-C-(hydroxymethyl)-D-threose (4) have been stereospecifically synthesized in one-step by a molybdic acid-catalysed isomerization reaction from respective D-xylulose (1) and D-ribulose (3). In the case of interconversion of 1 to 2, the content of the 2-C-branched chain tetrose in the equilibrium mixture can be doubled if boric acid is present in the reaction mixture in addition to the catalyst.