Synthesis of pyridazine derivatives. XXI. Tetrazolo-azido transformations in some fused azolopyridazines

6-Azidotetrazolo[1,5-b]pyridazine (III) has been prepared by two different routes and is easily transformed into the 6-amino derivative (IV). The attempted cyclization of 6-hydrazinotetrazolo[1,5-b] pyridazine (II) into the postulated tricycle has been shown to result in the formation of 6-azido-s-triazolo [4,3-b]pyridazine (VI), obtained also in a separate experiment from VII. The azido structure of VI has been confirmed from spectroscopic data and from its conversion into 6-amino-s-triazolo [4,3-b]pyridazine (VIII), obtained in another experiment from VII. Similarly, cyclization of II with cyanogen bromide resulted in the simultaneous formation of the s-triazolo ring and ring opening of the fused tetrazolo ring, giving IX. For 6-azido-2-phenylimidazo[1,2-b]pyridazine (XII) the expected azide structure proved to be correct.     

Sixth-order many-body perturbation theory. I. Basic theory and derivation of the energy formula

The general expression for the sixth-order Møller-Plesset (MP6) energy, E(MP6), has been dissected in the principal part A and the renormalization part R. Since R contains unlinked diagram contributions, which are canceled by corresponding terms of the principal part A, E(MP6) has been derived solely from the linked diagram terms of the principal part A. These have been identified by a simple procedure that starts by separating A into connected and disconnected cluster operator diagrams and adding terms associated with the former fully to the correlation energy. After closing all open disconnected cluster operator diagrams, one can again distinguish between connected and disconnected energy diagrams, of which only the former lead to linked diagram representations and, therefore, contributions to E(MP6). The connected diagram parts of A have been collected in four energy terms E(MP6)₁, E(MP6)₂, E(MP6)₃, and E(MP6)₄. The sum of these terms has led to an appropriate energy formula for E(MP6) in terms of first- and second-order cluster operators. © 1996 John Wiley & Sons, Inc.     

s-Triazines. I. Linear,sulfur bridged-s-triazine oligomers

A number of new thioether and disulfide oligomers of s-triazine have been prepared and identified. The reactions between 2,4-diphenyl-s-triazine-6-thiol and chloro substituted-s-triazines are described. A suggested mechanism for the formation of 2,2′-thiobis-(4,6-diphenyl-s-triazine) from 2,4-diphenyl-s-triazine-6-thiol is discussed.     

Myrochromanol und Myrochromanon,zwei weitere Metaboliten von Myrothecium roridum Tode ex Fr. Verrucarine und Roridine, 25. Mitt.

From cultures of Myrothecium roridum Tode ex Fr. myrochromanol ( 1 ) and myrochromanone ( 3 ), two new substituted chromanes, have been isolated. Their structures as 2-(1-propenyl)-4-hydroxy-6-methyl-chromane and 2-(1-propenyl)-4-oxo-6-methyl-chromane respectively, have been determined using spectroscopic techniques and by degradation to 2-hydroxy-5-methylbenzoic acid ( 6 ). The stereochemistry of 1 and 2 is deduced by NMR., CD. and by partial resolution ( Horeau method).     

Norbornanes. Part 10. Solvolysis of the Stereoisomeric 6-Cyano-2-norbornyl p-Toluenesulfonates. A Correction

The solvolysis products of the stereoisomeric 6-cyano-2-norbornyl p-toluene sulfonates 1 - 4 (R ? CN) in dioxane/water 7 : 3 have been determined. In contrast to an earlier report the 6exo-cyano-2exo-norbornyl p-toluenesulfonate ( 1 ; R?CN) yields 30% of the 2endo-alcohol 9 (R?CN) beside the 2exo-alcohol 10 and the norbornenes 12 and 13. The results confirm that - I substituents at C(6) reduce 1,3-bridging in the intermediate norbornyl cation and hence its rate of rearrangement. The relatively high rate constants for some 6-fluoro- and 6-cyano-2exo norbornyl p-toluenesulfonates are ascribed to C, C-hyperconjugation assisted by the conjugative effects of the 6-fluoro and cyano substituents.     

Dérivés C-glycosyliques. XXIV. Glycosyl-4-thiazoles

4-C-glycosylthiazoles have been prepared by reacting thiourea or thioacetamide with a 6-S-benzyl-6-chloro-1,2-O-isopropylidene-3-O-methyl-α-D-xylo-6-thiohexofuranos-5-ulose (7). The latter compound which constitutes an interesting synthetic intermediate in carbohydrate chemistry has been obtained by successive oxidation and chlorination of 6-S-benzyl-1,2-O-isopropylidene-3-O-methyl-α-D-6-thioglucofuranose.     

Synthese und Hydrolyse von 6endo-substituierten p-Toluolsulfonsäure-[2endo-norbornyl]estern. Norbornanreihe, 9. Mitteilung

The Synthesis and Hydrolysis of 6endo-Substituted 2endo-Norbornyl p-Toluenesulfonates The hydrolysis products of the p-toluenesulfonates of several hitherto unknown 6endo-substituted 2endo-norbornanols have been determined.     

Die Herzglykoside des Pfeilgiftes von Lophopetalum toxicum LOHER. 13. Mitteilung über Celastraceen-Inhaltsstoffe

The Heart Glycosides of the Arrow Poison of Lophopetalum toxicum LOHER From the cytotoxic and positive inotropic acting bark extract of the Philippinan Lophopetalum toxicum eight heart glycosides have been isolated and their structures have been elucidated mainly by field-desorption-MS- and ¹- and ¹³C-NMR spectroscopy. Besides the known k-Strophanthidin ( 1 ), Antiarigenin ( 6 ) and β-Antiarin (Antiarigenin-3-β-O-α-L -rhamnoside, 10 ) the following mono- and diglycosides could be identified: strophanthidin-3-β-O-α-6-desoxy-D -allopyranoside (strophalloside, 2 ), strophanthidin-3-β-O-β-6-desoxy-D -glucopyranoside (= Strophanthidin chinovoside, 3 ), strophanthidin-3-β-O[-4Oβ-D -allopyranosyl-β-6-desoxy-D -allopyranoside] ( 4 ), strophanthidin-3-β-O-[3-O-β-D -glucopyranosyl-β-6-desoxy-D -talopyranoside] ( 5 ), antiarigenin-3-β-O-[3-O-β-D -gulopyranosyl-β-6-desoxy-D -talopyranoside] ( 7 ), antiarigenin-3-β-O-[4O-β-D -allopyranosyl-β-6-desoxy-D -allopyranoside] ( 8 ), and antiarigenin-3-β-O-β-6-desoxy-D -allopyranoside (antiallosid) ( 9 ). The structure of strophanthidinchinovoside ( 3 ) could be confirmed by synthesis.     

Die Synthese von 6exo-substituierten p-Toluolsulfonsäure-[2exo-norbornyl]estern. Norbornanreihe, 1. Mitteilung

The Synthesis of 6 exo -Substituted 2 exo -Norbornyl p -Toluenesulfonates A number of hitherto unknown 6exo-substituted 2exo-norbornanols and their p-toluenesulfonates have been prepared by functionalization of intermediate norbornenes.     

1,2,5-Selenadiazoles. Synthesis and properties

4-Amino-1, 2, 5-selenadiazole-3-carboxylic acid and 4-amino-1, 2, 5-selenadiazole-3-carboxamides have been prepared by ring-cleavage of [1, 2, 5]selenadiazolo[3, 4-d]pyrimidin-7(6H)-one by basic reagents. The primary amide (III), as well as an N-alkyl amide, may be produced by the action of a primary amine. Hydrazine reductively cleaves the selenadiazole ring. The preparation of similar 4-ureido derivatives by ring-cleavage of [1,2,5]selenadiazolo[3, 4-d]pyrimidine-5, 7(4 H, 6H)-dione has been demonstrated with two examples. N-Butyl-4-ureido-1, 2, 5-selenadiazole-3-carboxamide is easily hydrolyzed in aqueous base to the corresponding acid, and it has been shown that this reaction proceeds by way of [1, 2, 5]selenadiazolo[3,4-d]pyrimidine-5, 7 (4H, 6H)-dione. The 4-amino-1, 2, 5-selenadiazole-3-carboxylic acid derivatives have marked cytotoxic, antibacterial, and antifungal activity.     

Studies on novel heterocyclic ring systems. Reaction of 4-hydroxylcoumarin with o-aminobenzaldehyde and 2-mercaptoaniline

Reactions of 4-hydroxycoumarin ( 1 ) with o-aminobenzaldehyde ( 2 ) and 2-mercaptoaniline ( 5 ) have been investigated. The yet unreported 6,12-dihydro-l-benzopyrano[3,4-b][1,4]benzothiazin-6-one ( 6 ) system has been synthesized and characterized on the basis of spectral and analytical data. A novel synthetic route to 6H-l-benzopyrano[4,3-b]quinolin-6-one ( 4 ) is reported. HMO calculations predict the most reactive sites on the molecules.     

Application of photoelectron spectroscopy to biologically active molecules and their constituent parts. II. 1,4-Benzodiazepines

The Hel photoelectron (PE) spectra of 5-phenyl-7-chloro-2H-1,4-benzodiazepin-2-one ( 1 ), its 1-methyl derivative ( 2 ), 3-hydroxy derivative ( 3 ), 1-methyl-3-hydroxy derivative ( 4 ), 3-(S)-methyl derivative ( 5 ), and 1-methyl-3-(S)-methyl derivative ( 6 ) have been recorded. The electronic structure of these compounds is discussed on the basis of the observed ionization energies, and of the semiempirical CNDO/2 calculations on model compounds 1a-6a , which have a hydrogen instead of the phenyl group in the 5-position. As a result the character of the seven highest occupied orbitals in 1–6 have been assigned.     

New heterocyclic ring systems. XII. Synthesis of [1,4]thiazinocarbazoles

Five [1,4]thiazinocarbazoles have been synthesized from 6-, 7- and 8-amino-2H[1,4]benzo-thiazin-3(4H)ones by the Jaap-Klingemann reaction with 2-hydroxymethylenecyclohexanone followed by Fischer indolisation of the resulting hydrazones. The structures of the hitherto unknown ring systems have been confirmed by pmr spectral data.     

Pteridines. Part XCVII. Synthesis and properties of 6-thioxanthopterin and 7-thioisoxanthopterin

6-Thioxanthopterin ( 13 ) was synthesized in four steps starting from 2-amino-4-(penthyloxy)pteridine ( 3 ) via the 8-oxide 4 , its subsequent interconversion to the 6-chloro ( 7 ) and 6-thio derivative ( 12 ) and final hydrolysis of the pentyloxy group. 7-Thioisoxanthopterin ( 15 ) was derived analogously from 2-amino-4-(pentyloxy)pteridine-7(8H)-thione ( 14 ) by alkaline hydrolysis. The various 6- and 7-thiopteridines were methylated to give the corresponding 6- ( 10, 11 ) and 7-(methylthio) derivatives ( 16, 17 ). The newly synthesized compounds have been characterized by elemental analyses, their UV spectra, and the determination of the acidic and basic pK_a values. The spectral relationships are discussed in detail.     

Pteridines. Part LXXXV. Chemical synthesis of deoxysepiapterin and 6-acylpteridines by acyl radical substitution reactions

A new synthesis of deoxysepiapterin ( 2 ), one of the two yellow eye pigments of the Drosophila mutant sepia, is described. The synthetic approach makes use of a homolytic nucleophilic acylation of 7-(alkylthio)pteridine derivatives ( 11, 13, 15, 18, 20 ) leading to the corresponding 6-acyl derivatives ( 21–27 ). Desulfurizations have been achieved for the first time in the pteridine series using Raney-Co,Raney-Cu, or Cu? Al alloy in alkaline medium. Besides cleavage of the C(7)? S bond, further reductions of the C?O group at C(6) and the C(7)?N(8) bond are detected as side reactions leading to 6-(1-hydroxyalkyl) ( 34, 35, 42, 43 ) and 6-acyl-7,8-dihydro derivatives ( 2, 36, 37 ), respectively, The newly synthesized compounds have been characterized by elemental analysis, p_K determination, UV and ¹H-NMR spectra.     

Derivatives of sym-Triazines. 6. Some Special Features of the Addition of Substituted Acetylenes to Triazine Monoazides

The special features of the interaction of 2-azido-4-R-6-R'-sym-triazines with some acetylenic compounds have been investigated. A series of new derivatives of sym-triazine linked at position 2 with a 1,2,3-triazole ring has been synthesized.     

Über Pterinchemie. 85. Mitteilung. Polyacetylierte 5,6,7,8-Tetrahydro-D- und -L-neopterine. Ein besonderer Fall von N(5)-Alkylierung des 5,6,7,8-Tetrahydroneopterin-Gerüstes

Polyacetylated 5,6,7,8-Tetrahydro-D - and L -neopterins. A Special Case of N(5)-Alkylation of 5,6,7,8-Tetrahydroneopterins Improved conditions are reported for the preparation of the earlier described (6R)- and (6S)-1′-O,2′-O,3′-O,2-N,5-pentaacetyl-5,6,7,8-tetrahydro-L -neopterins, one of which could be obtained as pure crystals. Its structure, determined by X-ray-diffraction analysis, corresponds to the (6R)-enantiomer. The method has also been used to make the corresponding D -diastereoisomers. Further acetylation of (6RS)-1′-O,2′-O,3′-O,2-N-tetraacetyl-5,6,7,8-tetrahydro-D -neopterin under drastic conditions yields a mixture of several polyacetylated D -neopterin derivatives and a polyacetylated ethyl-tetrahydro-D -neopterin which was isolated in crystalline form and established by X-ray-diffraction analysis to be (6R)-1′-O,2′-O,3′-O,4-O,2-N,2-N,8-heptaacetyl-5-ethyl-5,6,7,8-tetrahydro-D -neopterin.     

Pyridazines. IV. The synthesis and some reactions of acetylpyridazines

Two 3-acetylpyridazines have been prepared. N-Oxidation of 3-acetylpyridazine ( 6 ) gave only 3-acetylpyridazine 1-oxide ( 7 ). During the N-oxidation of 3-acetyl-6-methoxypyridazine ( 10 ), three primary products, namely, 3-acetyl-6-methoxypyridazine 1-oxide ( 12 ), 3-acetyl-6-methoxy-pyridazine 2-oxide ( 13 ), 3-acetylpyridazin-6-one ( 14 ) and an artifact, 3-methoxypyridazine 1-oxide ( 15 ) were obtained. Furthermore, it has been shown that 3-methoxypyridazine 1-oxide ( 15 ) can be obtained in quantitative yield by treatment of 3-acetyl-6-methoxypyridazine 2-oxide ( 13 ) with dilute sodium hydroxide solution at room temperature. This represents a novel deacylation reaction. Nitration of 3-acetylpyridazine 1-oxide, ( 7 ) gave 3,4-bis(3′-pyridazinoyl)furoxan 1′,1′-dioxide ( 19 ) rather than a simple nitration product. 3-Acetyl-pyridazine ( 6 ) and 3-acetyl-6-methoxypyridazine ( 10 ) also gave furoxans ( 22 and 23 ) upon nitration.     

Pteridines. Part XLI. Synthesis and properties of 6,7,8-trimethyl-4-thiolumazine

The first representative of the 8-substituted 4-thiolumazine series has been synthesized. In a sequence of reactions, 4,6-dichloropyrimidin-2-(1H)-one ( 1 ) is first converted into 4-chloro-6-(methylamino)pyrimidin-2(1H)-one ( 6 ), then the Cl-atom displaced by the thioxo group (→7) followed by a coupling reaction with 4-chlorophenyldiazonium chloride to introduce the necessary N-function into the 5-position (→ 9 ; Scheme 1). Reduction of the p-chlorophenylazo group leads to the 6-(methlyamino)-4-thiouracil-5-amine ( 10 ) which on condensation with diacetyl gives 6,7,8-trimethyl-4-thiolumazine ( 8 ). The physical properties of 8 are compared with the 2-thio analog and 6,7,8-trimethyllumazine indicating that 8 possesses the highest acidity and the longest UV absorption.     

Pteridine. Teil LXXX. Synthese,Reaktionen und Photochemie von Pteridinthionen

Synthesis, Reactions, and Photochemistry of Pteridinethiones The pteridine-6(5H)-thione 1 and various pteridine-7(8H)-thiones ( 13, 22, 26 ) have been synthesized, and their photochemical reactivity has been investigated under aerobic conditions. The formation of different photooxidation products is pH-dependent. In acidic to neutral media, disulfides ( 2, 15, 23, 29 ) are formed, whereas neutral to alkaline solutions favour the formation of pteridinesulfinic ( 3, 17 ) and -sulfonic acids ( 6, 16, 24, 30 ). Prolonged irradiation of the disulfides 2 and 15 led to the intensively yellow fluorescing bis(thio)dilumazines 19 and 20 , respectively.