HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Rolf Huisgen's Special Issues, Vol. 40, No. 2, 1995
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■ Isolation and Structure of the Human Cancer Cell Growth Inhibitory Phakellistatin 4 from the Western Pacific Sponge Phakellia Costata
George R. Pettit, Jun-ping Xu, Zbigniew Cichacz, Jean M. Schmidt, Ann-Christine Dorsaz, Michael R. Boyd, and Ronald L. Cerny
*Cancer Research Institute, Department of Chemistry and Biochemistry, Arizona State University, Main Campus, P.O. Box 872404, Tempe, AZ 85287-1604, U.S.A.
Abstract
Structural elucidation by high field 2D nmr and FAB-ms/ms techniques led to cyclo-(Pro-Thr-Pro-Phe-Ile-Phe-Ser) as the assignment for phakellistatin(4) a new cell growth inhibitory peptide from the Chuuk Archipelago marine sponge Phakellia costata.
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■ Face Selectivity in Diels-Alder Reaction of 4-Substituted Semicyclic Dienes with Dienophiles
Shigeru Nagashima, Yumiko Takaoka, Kumiko Kawakami, Motoo Shiro, and Ken Kanematsu
*Institute of Synthetic Organic Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Abstract
Face selectivity in Diels-Alder reactions of the semicyclic dienes (1a) and (1b) with maleic anhydride (MA) and N-phenylmaleimide (NPM) was examined. Cycloaddition reaction of 1 with MA occurred preferentially from the diene face anti to the allylic hydroxy group, on the other hand, the cycloaddition with NPM occurred preferentially from the syn to the hydroxy group.
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■ Thermal Reactions of 2-Cyclopropyl-2H-azirines
Kazuaki Isomura, Hideshi Kawasaki, Kenji Takehara, and Hiroshi Taniguchi
*Department of Chemical Engineering, Kitakyushu National College of Technology, Shii, Kokuraminami-ku, Kitakyushu 803, Japan
Abstract
Thermal rearrangement of 2H-azirines having a cyclopropane ring was revealed to give pyridines. Ene reaction involving a C=N bond to form tricyclic compound was observed in the case of 2-cyclopropyl-2H-azirine having an isobutenyl group cis to the azirine ring, whereas the trans isomer gave a pyridine ring exclusively.
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■ A Pericyclic Cascade in the Addition of Diphenyl Nitrile Imine to Pyridine
Pierluigi Caramella, Anna Gamba Invernizzi, Eros Pastormerlo, Paolo Quadrelli, and Antonino Corsaro
*Dipartamento di Chimica Organica, Università de Pavia, V. le Taramelli 10, 27100 Pavia, Italy
Abstract
On refluxing in benzene in the presence of excess pyridine monocycloadduct of diphenyl nitrile imine to pyridine smoothly undergoes a [1,5] sigmatropic shift and a subsequent electrocyclic opening to afford 1,2,4-triazole derivatives.
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■ Synthesis of New Bis-Crown Ethers That Show Specific Metal Ion Transport Properties
Kiyoshi Matsumoto, Shinji Okuno, Hirokazu Iida, and James W. Lown
*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-Nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
A variety of bis-crown ethers were prepared in moderate to good yields (46-95%) by high pressure SNAr reactions (0.8 GPa, 100°C). Some of them have indicated specific transport properties for Ag+ ion.
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■ Asymmetric Syntheses of O-Methylaphanorphine
Albert I. Meyers, Wolfgang Schmidt, and Braulio Santiago
*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.
Abstract
Two routes leading to the preparation of racemic, (+), and (-) O-methylaphanorphine via the asymmetric alkylation of 2-oxazolines are described.
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■ Reactions of Azapyrylium Ions with Nucleophiles: From Crazy products to a Novel Pyridine Synthesis
Kai Homann, Reinhold Zimmer, and Hans-Ulrich Reissig
*Institut of Organic Chemistry, Technical University Dresden, D-01062 Dresden, Germany
Abstract
Reaction of an azapyrylium ion as generated from a 6H-1,2-oxazine provided a β-azidoaldehyde by subsequent substitution, [3,3] sigmatropic rearrangement, and retro-Diels-Alder reaction. With moderately electron-rich alkynes azapyrylium ions react in a Diels-Alder reaction with inverse electron demand, and after fragmentation of a formyl cation pyridine derivatives are formed. Mechanism, scope and limitations of this novel pyridine synthesis are discussed.
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■ Palladium-mediated Carbomacrolactonization of Terminal Hydroxyacetylenes and Its Utilization for a Synthesis of Exaltolide
Masaki Setoh, Osamu Yamada, and Kunio Ogasawara
*Pharnaceutical Institute, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan
Abstract
Carbomacrolactonization took place to give macrolactoneacetylenes when terminal hydroxyacetylenes were stirred under atmospheric pressure of carbon monoxide at room temperature in the presence of palladium(II) acetate and triethylamine. Using 15-pentadecyn-2-olide obtained, exaltolide was synthesized on catalytic hydrogenation.
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■ 1,3-Dipolar Cycloadditions of Azidoalkylphosphonates to Enamines. Synthesis of Δ2-1,2,3-Triazolines and Triazoles
Francisco Palacios, Ana Ma Ochoa de Retana, and Jaione Pagalday
*Departamento de Química Orgánica, Facultad de Farmacia, Universidad del País, Vasco, Apto. 450, 01006 Vitoria, Spain
Abstract
5-Amino-Δ2-1,2,3-triazolines (3) and 1,2,3-triazoles (4) and (8) derived from aminoalkylphosphonates have been obtained in a regioselective fashion, by treating diethyl azidoalkylphosphonates (1) with enamines (2) and (6). Reaction of azidomethylphosphonate (1) with an excess of norbornadiene yields triazoline (10). This monoadduct undergoes nitrogen evolution and retro Diels-Alder reaction to give aziridine (11) and triazole (12), respectively.
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■ Novel Synthesis of Quinoline Derivatives by Zirconium-Promoted Cyclization
Miwako Mori, Alice Emi Imai, and Noriaki Uesaka
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
Zirconium-promoted cyclization of the diene (1) resulted in the perhydroquinoline derivatives (2a) and (3a) in moderate yields. The intermediary zirconacycles can be converted into the iodinated products (2c) and (3c) by treatment with iodine, and into the tricyclic ketones (12) by treatment with carbon monoxide.
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■ Synthesis of Alkano-1H-imidazo-azepine Derivatives from 3,6-Alkano-oxepines
Brigit Karl and Werner Tochtermann
*Institute of Organic Chemistry, University of Kiel, Ott-Hahn-Platz 4, D-24098 Kiel, Germany
Abstract
The title compounds (3a) and (3b) have been synthesized by reaction of the dihydromethoxyoxepines (1a) and (1b) with glycine methyl ester hydrochloride.
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■ The π-Donor Ability of Vinamidine Chelates (Co, Ni, Cu, Zn, Pd) Assessed by X-Ray, IR and NMR
Rudolf Knorr, Reinald Zölch, and Kurt Polborn
*Institute of Organic Chemistry, University of Munich, Karlstrasse 23, D-80333, München, Germany
Abstract
Formyl groups were used as reporter substituents attached to positions with high Π-electron densities in the vinamidine moieties of a 2,3-dihydro-1,4-diazepinium cation (7a) and of five metal complexes (9a-e). X-Ray structure analyses of the latter indicated significant Π donation to the coplanar formyl groups but insignificant changes of the formyl geometry. Infrared wave numbers in solution revealed a weak Π donation from the vinamidinium system (7a) and a uniformly strong one from the metal bis(chelates) (9a-e), but infrared intensities were inconclusive. However, clear evidence emerged from the rates of aldehyde rotation at the vinamidine moieties, as measured for these diamagnetic or paramagnetic heterocycles by 1H nmr: The Π-donor chararacters were energetically quantified by comparisons of literature data with the rotational barriers 11.0 kcal/mol at vinamidinium (in 7a) and 14.7-15.8 kcal/mol at vinamidin(id)e (in 9a, b, d and e).
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■ Photoinduced Reactions of Benzo[b]phenazine
Elisa Fasani*, Mariella Mella, and Angelo Albini
*Dipartiment di Chimica Organica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy
Abstract
While the photochemistry of azines is generally dominated by hydrogen abstraction from nΠ* states, benzo[b]phenazine has low-lying ΠΠ* states and undergoes both [4+4] dimerization (the main product is the less hindered biplanemer (2), but a small amount of the alternative dimer (3) is also formed) and self-sensitized photo-oxygenation to yield the endo-peroxide (5) (better obtained with an added sensitizer). Compound (5) undergoes decomposition by O-O bond cleavage to yield the quinone (4) and the diol (6).
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■ A 15N NMR Study of N-Phenylazoles
J. Hodge Markgraf and Joseph P. Sadighi
*Department of Chemistry, Williams College, 47 Lab Campus Drive, Williamstown, MA 01267, U.S.A.
Abstract
The 15N chemical shifts for a series of eleven N-phenylazoles were determined. Assignments for a triazole and four tetrazoles were based on 15N enrichment at specific sites.
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■ Synthesis of Dimethylpyrazolo[1,2-a]benzotriazoles and of Methylpyrazolo[1,2-a]quinoxalines by Cyclization of 3,5-Dimethyl-1-(2-nitrenopenyl)pyrazoles
Angelo Albini, Gianfranco Bettinetti, and Giovanna Minoli
*Dipartiment di Chimica Organica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy
Abstract
The thermal and photochemical decomposition of a series of 5-substituted 1-(2-azidophenyl)-3,5-dimethylpyrazoles has been examined under a homogeneous set of conditions. Cyclization to pyrazolo[1,2-a]benzotriazole (via singlet nitrene) is an efficient process except when the phenyl substituent induces intersystem crossing to the azide triplet or compensates for its electrophilicity. On the contrary, cyclization to pyrazolo[1,2-a]quinoxaline (via triplet nitrene) is not a preparatively useful process, due to competition with dimerization to the azo derivatives and reduction to aminophenylpyrazoles.
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■ Acid Catalyzed Hydrolysis of Cyclic Benzophenone Acetals. Effects of Ring Size and Ring Substituent
Takumi Oshima, Shin-ya Ueno, and Toshikazu Nagai
*Institute of Chemistry, College of General Educatin, Osaka University, Toyonaka, Osaka 560-8531, Japan
Abstract
Rates of acid-catalyzed hydrolysis of 5- to 8-membered ring benzophenone acetals (1-4) in 80% dioxane-water(v/v) were dependent upon the ring size and the ring-substituted methyl group as well as the condensed-rings. These kinetic results are interpreted in terms of the ring strain, the stereoelectronic effects, and the hydrophobicity.
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■ 1,3-Dipolar Cycloaddition of Nitrile Oxides to 8-Azaheptafulvenes
Remo Gandolfi, Anna Gamba, and Paolo Grünanger
*Dipartiment di Chimica Organica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy
Abstract
Azaheptafulvenes (2) reacted readily with nitrile oxides (1) to give, as a rule, only adducts derived from a reaction involving the C=N moiety of 2. The adducts consisted of a mixture of rapidly equilibrating “spiro” and “condensed” isomers, i.e. 6€8, whose ratio was found to be dependent on substituents, temperature and solvent. The zwitterion (7) is an appealing intermediate both for cycloaddition and isomerisation. Decomposition of the adducts to benzene, R1CN and R2NCO provided evidence in favor of the presence of the “norcaradiene” derivatives (14) (undetectable by nmr) in equilibrium with 6 and 8. Only products arising from the “spiro” isomer (6) were obtained in high yields in the catalytic hydrogenation of 6/8.
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■ Azobridges from Azines XIII. Azobridged Polycycles: Skeletal Reaarangements by Denitrogenation of Triazolines and Solvolyses of Aziridines
Siegfried Hünig and Petra Kraft
*Institüte of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany
Abstract
Triazolines (2, 6 and 12) derived from the corresponding azobridged polycycles undergo rapid denitrogenation in the presence of several heterogeneous acids (e.g. silica gel) with formation of the aziridines (3, 7, and 13) together with the rearrangement products (4) and (8). In addition to 7 and 8, further products are formed on extrusion of nitrogen from 6 by dissolved acids, especially formic acid. In these reactions the azo group of 6 is involved, and hydrazine (9) and enamine (10) are produced. These two products are also isolated from the very slow acid catalyzed rearrangement of aziridine (7). The most likely reaction paths are exemplified with triazoline (6) in Scheme 1.
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■ An Aproach to the Synthesis of a Papaverine Analogue Containing a Quinazoline Ring System
Akira Miyashita, Hideaki Matsuda, Yoshiyuki Matsuoka, Ken-ichi Iwamoto, and Takeo Higashino
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
Synthesis of a papaverine analogue containing a quinazoline ring system (4-azapapaverine) was achieved. In the synthesis of 4-azapapaverine catalytic aroylation is a useful reaction. Preparation of several 4-aroyl-6,7-dimethoxyquinazolines was accomplished by aroylation.
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■ Heterocyclisation of 3-Trifluoroacetyllactams by Hydrazines
Jean-Philippe Bouliion, Anne-Marie Frisque-Hesbain, Zdenek Janousek, and Heinz G. Viehe
*Laboratoire de Chimie Organique, Université de Louvain, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium
Abstract
3-Trifluoroacetyllactams may heterocyclize with hydrazine or with its methyl or phenyl derivative either without ring opening to annelated trifluoromethylpyrazoles or by Ring Opening - Ring Closure (RORC) reaction to zwitterionic salts of 4-ω-alkylamino-5-hydroxy-3-trifluoromethylpyrazoles.
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■ Crosss-conjugated and Pseudo-Cross-conjugated Mesomeric Betaines, 19. Cycloaddition Products from Mesomeric Pyrimidiniumolates and TCNE and Their Thermal Ring Transformation Reaction
Thomas Kappe, Wolfgang Lube, Kurt Thonhofer, Christoph Kratky, and Ulrike G. Wagner
*Institute of Organic Chemistry, Karl-Franzens-University Graz, Heinrichstr. 28, A-8010 Graz, Austria
Abstract
The bicyclic pyrido-pyrimidine mesoion (2) reacts with TCNE under the loss of HCN to yield the tricyanovinylated derivative (3). However, monocyclic pyrimidine betaines (4a-d) (substituted at C-5) afford with TCNE 14-dipolar cycloaddition products (5a-d). Compounds (5c,d) (with CH2 groups at the malonyl moiety) rearrange above 200°C under the loss of HCN and phenyl isocyanate to yield cyclopenta[d]pyrmidines (6a,b).
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■ Preparation of beta-Lactams from beta-Hydroxy Amides, and Annulation of N-Malonyl beta-Lactams by Manganese(III) Acetate-promoted Free Radical Cyclization and by Aldol Cyclization
Peter J. Crocker, Ulrika Karlsson-Andreasson, Bruce T. Lotz, and Marvin J. Miller
*Department of Chemistry and Biochemistry, College of Science, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
Abstract
β-Lactams are formed from β-hydroxy amides by base-promoted cyclization of the β-methylsulfonoxyamide. In the system studied, this amide-based mesylate cyclization proceeded in high yields, whereas the analogous β-chloroamide afforded only the α,β-unsaturated amide. Also, two new methods of synthesizing carbacephams by annulation of malonate-substituted β-lactams were demonstrated. The first was a manganese(III) acetate-promoted oxidative free radical cyclization. The second was a spontaneous aldol cyclization of an intermediate aldehyde generated by ozonolysis of an alkene.
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■ Syntheses of Racemic and Enantiomeric (S)-(+)-4,5,6,7-Tetrahydro-5-methyl-imidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one Derivatives
Hans Rudolf Pfaendler and Frank Weisner
*Institute of Organic Chemistry, University of Munich, Karlstrasse 23, D-80333, München, Germany
Abstract
Racemic and enantiomeric (S)-(+)-4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one derivatives were prepared using free amino acids and 3-nitroisatoic anhydride. Simultaneous reduction of two amide functions was efficiently achieved using diborane.
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■ The Application of Symmetrical Vinamidinium Salts to the Preparation of Monosubstituted Triazolo[1,5-a]pyrimidines
Scott A. Petrich, Zhenrong Qian, Lisa M. Santiago, John T. Gupton,* and James A. Sikorski
*Department of Chemistry, University of Central Florida, Orlando, Florida 32816, U.S.A.
Abstract
The reaction of 2-substituted vinamidinium salts with 3-amino-1,2,4-triazole under basic conditions to yield 6-substituted triazolo[1,5-a]pyrimidines is described.
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■ Reactions of an o-Quinone Monoimide with Pyrroles
Harold W. Heine, Matthew G. LaPorte, Robert H. Overbaugh, and Elizabeth A. Williams
*Department of Chemistry, Bucknell University, Lewisburg, PA 17837, U.S.A.
Abstract
The o-quinone monoimide (7) undergoes inverse electron demand Diels-Alder reactions with 1-benzenesulfonyl- and 1-carbomethoxypyrroles. The initial adduct (9), formed when 7 interacts with 1-carbomethoxypyrrole, underwent a further cycloaddition with 7 yielding a 2:1 adduct (10). Similar 2:1 adducts result when 7 reacts with 1-methyl-2-acetyl- and 1-methyl-2-carbomethoxypyrroles. Compound (7) reacts formally as an electrophile when it is admixed with 1-methyl- and 1-methyl-3-acetylpyrroles to give substituted pyrroles.
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■ Cyclization of the Ene Reaction Products from Hexafluoroacetone Imine: Synthesis of Bis(trifluoromethyl)pyrrolidine Derivatives
Tetsuo Shimada, Akihiro Fujimoto, Toshiyuki Takagi, Mayumi Koyama, Akira Ando, and Itsumaro Kumadaki
*Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan
Abstract
N-Tosylhexafluoroacetone imine reacted as a good enophile with ene components to give α,α-bis(trifluoromethyl)homoalIylamine derivatives. Cyclization of the ene reaction products in the presence of p-toluenesulfonic acid gave α,α-bis(trifluoromethyl)pyrrolidine derivatives, when the δ position of the homoallylamino group was substituted with an aromatic ring, while no reaction occurred, when substituted with an alkyl group.
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■ Bispyridyl- and Bisquinolylmenthanes. NMR-based Charge Mapping of the Carbanions and Metal Ligand Properities
Alessandro Abbotto, Silvia Bradamante, Giorgio A. Pagani, Henry Rzepa, and Federica Stoppa
*Dipartimento di Chimica Organica e Industriale, Centro C. N. R., V. Venezian 19 I-20133 Milano, Italy
Abstract
Nmr evidence is obtained for mixtures of geometrical stereoisomers of carbanions in DMSO solution of bis(4-)- and bis(2-pyridyl)methane (1) and (2), bis(2-pyridyl)acetonitrile (3), and bis(2-quinolyl)methane (4). When incorporated into Π-charge/shift relationships the 13C and 15N nmr data provide access to charge demands cx of the heterocycles, that is the fraction of Π-charge withdrawn by the rings from the carbanionic carbon. Compounds (3) and (4) behave as ligands LH, whose anions L- produce neutral chelates with divalent metal ions (Met = Zn2+, Pd2+). With Met = Co2+, Cu2+, Mn2+ the ligand LH 3 affords the dimer L2.
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■ Silver Carbonate Promoted Reaction of Hydrazonyl Chlorides with Allylic Alcohols
Luisa Garanti, Giorgio Molteni, and Gaetano Zecchi
*Dipartimento di Chimica Organicane Industriale, dell'Universitè, Via Golgi 19, I-20133 Milano, Italy
Abstract
The title reaction affords two main kinds of products: (i) pyrazole derivatives due to cycloaddition of a nitrile imine intermediate to the ethylenic bond; (ii) open-chain carbonyl compounds due to the electrophilic attack of a nitrilium-like carbocation to the ethylenic bond. Mechanistic possibilities are discussed.
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■ Synthesis of 5-Isopropenyl/Vinyl Substituted Pyrimidinones via[4+2] Cycloaddition Reactions of 1,3-Diaza-1,3-butadienes with Isopropenyl/Vinyl ketenes and Their Further Transformations: [4+2] and Unusual [3+2] cycloadditions with α-nitrosostyrenes
Arun K. Sharma and Mohinder P. Mahajan
*Department of Chemistry, North-Eastern Hill University, Shillong-793003, Meghalaya, India
Abstract
1,3-Diaza-1,3-butadienes (1 and 5) underwent [4+2] cycloaddition reactions with isopropenyl/vinylketenes (2), acting as 2Π components, to result in pyrimidinones (4 and 7). The treatment of 5-isopropenyl substituted pyrimidinones with phosphorus pentasulfide in the presence of sodium carbonate in dry tetrahydrofuran gave pyrimidinones (8). The reactions of nitrosoalkenes with 5-vinyl substituted pyrimidinones resulted in [4+2] cycloadditions leading to 1,2-oxazines (15), whereas 5-isopropenyl substituted pyrimidinones resulted in unusual [3+2] cycloaddition reactions yielding the nitrones (14).
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■ Synthesis of 1,5-Substituted Tetrazoles from Secondary Thioamides
Stefan Lehnhoff and Ivar Ugi
*Institut für Organische Chemie und Biochemie, Technische Universität München, Lichtenbergstrasse 4, D-85747 Garching, Germany
Abstract
A new, rather simple method for the conversion of thioamides and similar structures into 1,5-substituted tetrazoles is described. The procedure employs TMS-N3 and a mild Lewis acid, like SnCl4, in an inert solvent at room temperature and leads to high yields. Such compounds are of increasing interest for their pharmaceutical properties.