HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Regular Issue
Vol. 38, No. 4, 1994
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■ CNS Agents: Optical Resolution with Baker’s Yeast as Key Step in the Synthesis of Optically Active Tricyclic Amines
Bernhard Wünsch* and Heike Diekmann
*Institut für Pharmazie, und Lebensmittel chemie Universität München, Sophienstraße 10, D-80333 München, Germany
Abstract
The synthesis of the optically active 1,5-epoxy-3,4,5,6-tetrahydro-N-methyl-1H-2-benzoxocin-6-amines ((-)-10) and ((+)-10) is achieved by optical resolution of the racemic 1,5-epoxy-4,5-dihydro-1H-2-benzoxocin-6(3H)-one ((±)-8) with baker’s yeast as the key step. (+)-10 can also be prepared starting with the homochiral α-hydroxy-γ-butyrolactone ((-)-6a), which is easily obtained from (S)-(-)-malic acid.
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■ Oxidation of Substituted Pyridines PyrCH2X (X=H, COOR, COC6H5) with Hypervalent Iodine Reagents
Ian P. Andrews, Norman J. Lewis, Alexander McKillop, and Andrew S. Wells*
*SmithKline Beecham Pharmacuticals, Old Powder Mills, Nr Leigh, Tonbridge, Kent, TN11 9AN, U.K.
Abstract
Oxidation of a variety of pyridines, PyrCH2X (X=H, COOR, COC6H5) with hypervalent iodine reagents PhI(X)(Y) (X=OH, Y=OTs; X=Y=CH3COO; X=Y=CF3COO) has been studied. Simple alkylpyridines are unaffected by the reagents, but 2- and 4-substituted derivatives PyrCH2X(X=COOR, COC6H5) are oxidised at the CH2 group.
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■ The Chemistry of Cyclic Tautomers of Tryptophan: Highly Diastereoselective Aldol Condensations
David Crich,* Isaura Pastrana-Gress, Leticia Quintero-Cortes, and Jesús Snadoval-Ramirez*
*Department of Chemistry (M/C 111), University of Illinois at Chicago, 845 West Taylor St. , Chicago, IL 60607-7061, U.S.A.
Abstract
Highly diastereoselective aldol reactions of a cyclic tryptophan tautomer (1) are reported, together with stereochemical assignments of the products and a possible rationale for the selectivity.
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■ On the Synthesis of the Oxindole Alkaloid: (±)-Horsfiline
Sophie-Isabelle Bascop, Janos Sapi, Jean-Yves Laronze,* and Jean Lévy
*Laboratoire de Transformation et Syntheses deSubstances Naturelles, UA CNRS 492, Faculté de Pharmacie, Université de Reims-Champagne-Ardenne, 51, rue Cognacq-Jay, F-51096 Reims Cedex, France
Abstract
Two syntheses of the title compound [(±)-1a] have been described: the first one is based upon the oxidative rearrangement of 7-methoxy-N-methyltetrahydro-γ-carboline (6a), while the second path involves a spirocyclization between 2-oxo-5-methoxytryptamine (18a) and formaldehyde.
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■ Model Experiments for Acetylation of the Marine Sponge Purines Agelasimine-A and Agelasimine-B
Tozo Fujii,* Tohru Saito, Jun Chikazawa, Masashi Ohba, and Tadamasa Date
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
Reaction of 7-benzyl-N6,3-dimethyladenine (1b) and 7-benzyl-1,2-dihydro-1,3-dimethyladenine (2b), selected as models for the marine sponge alkaloids agelasimine-A (1a) and agelasimine-B (2a), with acetic anhydride in pyridine have been studied. The product from 1b was the imidazole derivative (6b), whose structure was determined by an X-ray crystallographic analysis. The product from 2b was the N6-acetyl derivative (4b). On treatment with boiling H2O, 4b gave 7-benzyl-2,3-dimethylhypoxanthine (5b) and a compound presumed to be 11.
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■ Studies with Polyfunctionally Substituted Heteroaromatics: Arylhydrazononitriles for the Synthesis of Polyfunctionally Substituted Azines
Mohamed Hilmy Elnagdi, Ahmed Hafez Hussien Elghandour, Abdel Fattah Ali Harb, Abdel Haleem Mostafa Hussien, and Soud Abdel Meniem Metwally
*Department of Chemistry, Faculty of Science, Cairo University, Ginza, Egypt.
Abstract
The reaction of arylhydrazononitriles with naphthols, phenols and glycine is reported.
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■ Pyrrole[2,1-a]isoindole-5-ones and Benz[3,4]azocin-1(2H)-1,4,6-triones
Abraham Nudelman,* Dana Marcovici, and Ayelet Nachum
*Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel
Abstract
Pyrrolo[2,1-a]isoindol-5-ones (8) have been obtained by base catalyzed cyclization and O-alkylation of N-phthalimido-substituted β-keto ester (1) via intermediate (7). Reaction of 1 with MeI/acetone/K2CO3 gave the C-alkylation product (3). With bulkier reagents than MeI in a variety of solvents and in the presence of various bases, compounds (8) were isolated. In the absence of an alkylating agent, reaction of 1 with NaH/DMF gave pyrrolo[2,1-a]isoindol-5-one derivative (6), found at room temperature in its keto form (6a) and at higher temperatures in the enol form pyrrolo[2,1-a]isoindol-5-one-1-carboxy-2-hydroxy-3-methyl methyl ester (6b), and 11 which at room temperature already appeared in the enol form. Reaction of acyl chloride (14) with ethyl cyanoacetate/NaH did not stop at ethyl-2-cyano-4-N-isoindol-3-oxopentanoate (15) but proceeded to rearrange to a single diastereomeric benz[3,4]azocin-1(2H)-1,4,6-trione (17).
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■ Synthesis of Some Furyl- and Thienylacrylates or Diacrylates and Aacrylic Acids by the Palladium Catalysed Vinylation of Substituted Bromofurans and Bromothiophenes
Grace Karminski-Zamola,* Jasna Dogan, Miroslav Bajic, Jelena Blazevic, and Miroslav Malesevic
*Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulicev trg 20, P.O Box 177, HR-10000 Zagreb, Croatia
Abstract
Furyl- and thienylacrylates (8-14) and acrylic acids (8a, 10a-14a) are prepared in moderate yields by palladium catalysed coupling of substituted bromofurans and bromothiophenes with ethyl acrylate.
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■ The Synthesis of 3H-Azepines: Thermal Reorganization of 2,4- and 3,5-Di-t-butyl-3a,5a-dihydro-3H-cyclobuta[b]pyrroles to 2,5- and 3,6-Di-t-butyl-3H-azepines
Kyosuke Satake,* Hidekazu Saitoh, Masaru Kimura, and Shiro Morosawa
*Department of Chemistry, Faculty of Science, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
Thermal reaction of cyclobuta[b]pyrroles, which derived by photochemical cyclization of methyl 2,5- and 3,6-di-t-butyl-1H-azepine-1-carboxylate gave di-t-butyl substituted 3H-azepines. The kinetics of the reaction were measured and the activation energy of the reorganization to 3H-azepines was estimated.
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■ An Improved Synthesis of 5-Alkyl-2,3-dihydrofuran-2,3-diones
C. Oliver Kappe,* Gert Kollenz, and Curt Wentrup
*Institute for Organic Chemistry, Karl-Franzens-University Graz, Heinrichstrasse. 28, A-8010 Graz, Austria
Abstract
The synthesis of 5-tert-butyl-2,3-dihydrofuran-2,3-dione (2a) from ethenyloxysilane (3) and oxalyl chloride is reinvestigated. Apart from 2a, two other reaction products, namely furan-3-yl oxalate (6) and difuran-3-yl oxalate (6) and difuran-3-yl oxalate (7) are isolated, explaining the low yield of 2a in this process. An improved method for the preparation of 2a, and its 5-methyl analog (2b) by cyclization of acylpyruvic acids (8a,b) is described.
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■ 1,3-Dipolar Cycloadditions of Pyridinium Dicyanomethylide under Microwave Irradiation
Angel Díaz-Ortiz, Enrique Díez-Barra, Antonio de la Hoz,* André Loupy, Alain Petit, and Luis Sánchez
*Facultad de Quimica, Universidad de Castilla-La Mancha, Campus Universitario, 13071 Ciudad Real, Spain
Abstract
Microwave irradiation induces a specific effect on the reactivity on the title reaction. Selectivity may be increased using a neutral bentonite as support.
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■ Selective Alkylations of 1,2,4-Triazole and Benzotriazole in the Absence of Solvent
David Abenhaïm, Enrique Díez-Barra,* Antonio de la Hoz, André Loupy, and Ana Sánchez-Migallón
*Facultad de Quimica, Universidad de Castilla-La Mancha, Campus Universitario, 13071 Ciudad Real, Spain
Abstract
Alkylation of 1,2,4-triazole and benzotriazole has been performed either in basic media under solvent free phase transfer catalysis conditions or in the absence of base by conventional and microwave heating, Several parameters affecting the selectivity have been studied. In the case of triazole alkylation, microwave irradiation produces specific (non thermal) effects both on reactivity and selectivity.
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■ A Convenient Synthesis of 5-Trifluoromethyl-3-thiazolines and 5-Trifluoromethyl-2,3,4,5-tetrahydro-1,2,4-triazines
Yasuhiro Kamitori, Masaru Hojo, Ryoichi Masuda,* Toshiya Takahashi, Masaaki Wada, Takehiro Hiyama, and Yoshio Mimura
*Department of Industrial Chemistry, Faculty of Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
Abstract
5-Trifluoromethyl-3-thiazolines (3) and 5-trifluoromethyl-2,3,4,5-tetrahydro-1,2,4-triazine (5) were conveniently synthesized from 3-(N-tert-butyl-N-methylhydrazono)-1,1,1-trifluoroalkan-2-ones (1) with the use of silica gel as an effective catalyst. 5-Trifluoromethylimidazole (6) was also abtained in good yield from 1.
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■ Pyrrolo[1,2-a]thieno[3,2-f][1,4]diazepines: New 4H and 4H-5,6-Dihydro Derivatives
Isabelle Rault, Sylvain Rault, and Max Robba*
*Centre d’ Etudes et de Recherche , Sur le Médicament de Normandie (CERMN), 5, rue Vaubénard, 14032 Caen Cedex, France
Abstract
Synthesis of 4H and 4H-5,6-dihydro pyrrolo[1,2-a]thieno[3,2-f][1,4]diazepines from 3-[2-(1-pyrrolyl)thienyl]benzylamine is described.
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■ Halogenated 2H-1-Benzopyrans: Syntheses and Reactivity toward Aluminium, Magnesium, and Lithium Organometallics
Ángel Alberola, Blanca Calvo, Alfonso González-Ortega,* Cristina López, and Fernando Villafañe
*Deparamento de Química Orgánica, Facultad de Ciencias, Universidad de Valladolid, 47005 Valladolid, Spain
Abstract
3-, 4-, or 6-Halo-2H-1-benzopyrans are prepared by reacting the halogenated coumarins with lithium, magnesium or aluminium organometallics, and further thermal cyclization of the resulting o-hydroxycinnamyl alcohols. The method is not applicable for 3-halo-2H-1-benzopyrans with no-substituents on C-2. The 3-, or 4-halo-2H-1-benzopyrans derivatives give mono-metallated products when the species obtained are subjected to metal-halogen interchange with butyllithium, whereas the 6-bromo derivatives afford 6-lithium-2H-1-benzopyrans.
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■ Norditerpenoid Alkaloids from the Aerial Parts of Aconitum balfourii Stapf
Khadga S. Khetwal, Haridutt K. Desai, Balawant S. Joshi, and S. William Pelletier*
*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.
Abstract
From the aerial parts of Aconitum balfourii Stapf nine norditerpenoid alkaloids: condelphine (1), bullatine C (2), neoline (3), isotalatizidine (4), 1-O-methyldelphisine (5), pseudaconitine (6), yunaconitine (7), bikhaconitine (8), and indaconitine (9), were isolated. The identity of these alkaloids was determined by comparison of mp, tlc and ir spectra with those of authentic samples and the carbon-13 nmr spectra of 2,5,6,7 and 8 with the published chemical shifts. Detailed nmr spectral studies (1H, 13C, 1H homonuclear COSY, HETCOR, and selective INEPT) carried out on 1,3,4 and 9 have provided accurate chemical shift assignments for these alkaloids.
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■ From Penicillins to 4,5-Dioxothiazolidines: A Thermal Rearrangement of Tritylaminopenam Derivatives
Marco Alpegiani and Ettore Perrone*
*Pharmacia Farmitalia Carlo Erba Srl, 20014 Nerviano, Milano, Italy
Abstract
Thermolysis of p-nitrobenzyl 6β-tritylaminopenicillanate 1β-oxide (1) afforded (2R)-3-methyl-2-(4-oxo-5-tritylimino-3-thiazolidinyl)-3-butenoate (8), which could be easily converted into 4,5-dioxothiazolidines (9, 11). The influence of catalytic amounts of 2-mercaptobenzothiazole in promoting the rearrangement, and the isolation of the thiazolidinone (10) from thermolysis of a model azetidinone (17), suggest that the unusual scission of the C-5,C-6 bond originally present in penam (1) occurred at the level of tritylamino-1,2-secopenicillanates. A mechanism is proposed after the observation that the 6α-deuteriated penam (2) rearranged to the undeuteriated thiazolidinone (8), whilst epimeric 2-deuterio derivatives (18) were produced from 1 in the presence of D2O.
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■ Mo(CO)6-Induced N-O Bond Cleavage of Isoxazoles. A Convenient Route to Pyridin-4(1H)-ones
Makoto Nitta* and Takanobu Higuchi
*Department of Chemistry, School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
The Mo(CO)6-induced reaction of 3-methyl-5-(2-oxoalkyl)isoxazoles, which are derived through proton-abstraction of 3,5-dimethylisoxazole followed by treatment with esters, gave pyridin-4(1H)-ones in good to modest yields in a single step.
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■ Addition Reaction of Photoenols from o-Methyl-substituted Aromatic Ketones with 5-Alkylidene-1,3-dioxane-4,6-dione Derivatives
Takashi Tsuno* and Kunio Sugiyama
*Department of Industrial Chemistry, College of Industrial Technology, Nihon University, -2-1, Izumi-cho, Narashino, Chiba 275-8575, Japan
Abstract
Photolyses of 2-methylacetophenone or 2-methylbenzophenone with isobutylidene Meldrum’s acid or 5-isobutylidene-1,3-dioxane-4,6-dione derivatives produced novel adducts, bonding between the β-carbon of the acylals and the 2-methyl carbon of the aromatic ketones. However, the photoenol derived from benzocyclobutenols by thermolysis did not undergo the addition reaction with the acylal. The benzocyclobutenols reacted with isobutenylketene derived by pyrolysis of isobutylidene Meldrum’s acid to yield corresponding benzocyclobutenyl 4-methyl-3-pentenoate derivatives.
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■ A New and Efficient Synthesis of the μ-Selective Opioid Antagonist Cyprodime
Roland Krassnig and Helmut Schmidhammer*
*Institute of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria
Abstract
The μ-selective opioid antagonist cyprodime has been prepared in a six-step sequence starting from naltrexone. The 3-hydroxy group of naltrexone was removed via tetrazolyl ether (3) which was hydrogenated catalytically to give 17-cyclopropylmethyl-4,5α-epoxy-14-hydroxymorphinan-6-one (4). Methylation gave 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-6,14-dimethoxymorphinan (5) and hydrolysis of it 17-cyclopropylmethyl-4,5α-epoxy-14-methoxymorphinan-6-one (6). Reductive opening of the 4,5-epoxy bridge and methylation of the resulting phenol (7) yielded cyprodime (1).
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■ Synthesis of 2-Silatetralin Derivatives Bearing Oxygen Functional Groups
Osamu Hoshino,* Akihisa Hirokawa, Toru Taguchi, and Kenji Miyauchi
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12.Ichigaya Funagawara-machi, Shinjuku-ku, Tokyo 162, Japan
Abstract
The Grignard reagents of methoxy- or methylenedioxyphenylmethyl chlorides (12a-e) were treated with trichlorovinylsilane in THF or ether to give methoxy- or methylenedioxybenzyldichlorovinylsilanes (13a-e). The reaction of 13a-d in the presence of AlCl3 in CS2 or CH2Cl2 followed by treatment with MeOH and cyclohexylamine or Et3N afforded methoxy-2-silatetralins (16a-d). Treatment of 16a-d with MeMgI or EtMgBr in ether gave the corresponding 2,2-dimethyl- or 2,2-diethyl-2-silatetralins (17a-d or 18). Demethylation of 17a, 17b or 18 with BBr3 in CH2Cl2 furnished hydroxy-2-silatetralins (19a, 19b or 20).
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■ The Reactivity of Acridinium Salts and Related Compounds
Wanda Sliwa
*Institute of Chemistry and Environmental Protection, Pedagogical University, Al. Armii Krajowej 13/15, 42-201 Czestochowa, Poland
Abstract
Reactions of quaternary acridinium salts and of N-substituted acridan systems are presented, along with derivatives and acridinium salts applied as chemiluminescent agents or DNA intercalators.