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. 34, No. 5, 1992
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■ Synthesis of 5-Alkyl Substituted Uracil Derivatives from Barbituric Acid
Ilaria Candiani, Walter Cabri, Angelo Bedeschi,* Tiziano Martinengo, and Sergio Penco
*Farmitalia Carlo Erba-R&D, Via dei Gracchi, 35, 20146 Milan, Italy
Abstract
A new two step synthesis of 5-alkyluracil derivatives from barbituric acids is described. Regioselective mono O-mesylation of barbituric acids, followed by desulfonylation under reductive conditions, afforded uracils in high overall yield. The reductive desulfonylation step is also discussed.
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■ A Convenient, One-Pot Synthesis of Tropocoronands and Tropopodans by Use of the Heterocycle-Exchange Reaction of Benzo[b]cyclohepta[e][1,4]oxazine
Tetsuo Nozoe,* Kimio Shindo,* Hidetsugu Wakabayashi, and Sumio Ishikawa
*Department of Chemistry, Faculty of Science, Josai University, Sakado, Saitama 350-02, Japan
Abstract
Treatment of benzo[b]cyclohepta[e][1,4]oxzine (5) with 1.2 equiv. of α,ω-diaminoalkanes (2, n=4-12) in ethanol at 80 °C gave tropocoronands (4, n=4-12) in one step in high yields, while the reaction of 5 with an excess of 2 afforded tropopodands (6, n=4-6). The reactions of 5 with 2 (n=2,3) yielded bicyclic pyrazino or diazepino compounds in high yields. Coronands [14 (instead of 4a) and 4b (n=3)] were, however, obtained by the reaction of 5 with N-acetyldiaminoalkanes. The reaction of 5 with α,ω-amino alcohol afforded the corresponding podands.
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■ Sesquiterpene Pyridine Alkaloids from Maytenus ebenifolia
Hideji Itokawa,* Osamu Shirota, Hiroshi Morita, and Koichi Takeya
*Department of Pharmacognosy, Tokyo College of Pharmacy, Horinouchi 1432-1, Hachioji, Tokyo 192-03, Japan
Abstract
Three new sesquiterpene pyridine alkaloids, ebenifolines W-I(1), E-I(2), and E-II(3) were isolated from the stem barks of Maytenus ebenifolia Reiss. (Celastraceae). Their structures were elucidated by spectroscopic methods.
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■ Synthesis of 6-Phenylaminofuro[2,3-d]pyrimidine-2,4(1H,3H)-diones from Barbiturylbenzylidenes and Isonitriles
José Daniel Figueroa-Villar,* Carisa Lopes Carneiro, and Elizabete Rangel Cruz
*Seção de Química, Instituto Militar de Engenharia, Pç Gal. Tibúrcio 80 22290, Rio de Janeiro, RJ, Brazil
Abstract
Barbiturylbenzylidenes, prepared by Perkin condensation of aromatic aldehydes with 1,3-dimethylbarbituric acid, react with phenylisonitrile to yield four 5-aryl-6-phenylamino-1,3-dimethylfuro[2,3-d]pyrimidine-2,4(1H,3H)-diones.
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■ Efficient Catalytic Furylation of 2-Acetoxy-5-pyrrolidone
Tomihisa Ohta, Sojiro Shiokawa, Eiichiro Iwashita, and Shigeo Nozoe*
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980, Japan
Abstract
2-Acetoxy-5-pyrrolidone was furylated under a catalytic combination of zinc bromide and chlorotrimethylsilane. The effective catalyst system extremely accelerated the furylation reaction.
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■ Studies on Pyridinium N-Ylides: One Step Synthesis of Heteropolycycles, Indolizinoquinolizines
Yoshiro Matsuda,* Makoto Yamashita, Kimitoshi Takahashi, Shizuki Ide, Kazuki Furuno, Katsura Torisu, Takahiro Itou, and Chieko Motokawa
*School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852, Japan
Abstract
The heteropolycycles, indolizinoquinolizines (3,4) were obtained by the reaction of pyridylketene dithioacetal (1) with two molar equivalents of pyridinium salts (2a,b).
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■ Synthesis of a Bicyclic γ-Lactam Dipeptide Analogue
Jack E. Baldwin, Victor Lee, and Christopher J. Schofield
*The Dyson Perrins Laboratory and the Oxford Centre for Molecular Sciences, South Parks Road, Oxford, OX1 3QY, U.K.
Abstract
The asymmetric synthesis of a bicyclic γ-lactam analogue of a dipeptide, in which the key step was the bis-alkylation of an optically active diphenyloxazinone chiral glycine anion equivalent is described.
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■ 5,6-Dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2-ij]quinoline-2,2-dioxide: A New N,N’-Cyclic Sulfamide
Serge Mignani,* Claude Gueremy, Jean-Luc Malleron, Alain Truchon, Jean-François Peyronel, and Jean-Pierre Bastart
*RHONE-POULENC RORER, Centre de Recherches de Vitry-Alfortville, 13 Quai Jules Guesde-BP 14, 94403 Vitry-sur-Seine Cedex, France
Abstract
The title compound (1a) and its potassium salt (1b)were prepared in two steps, starting from 8-nitroquinoline.
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■ A New Synthesis of 1-Hydroxyisoindoles
Jean-Michel Vierfond,*Christian Martin, Yvette Mettey, Annick Reynet, and Marcel Miocque
*Laboratoire de Chimie Organique GREAM, Faculté de Pharmacie, 14 rue du Jardin des Plantes, POITIERS 86034, France
Abstract
Heteroarylmethylation of halogenobenzonitriles in the presence of air (O2) gives 1-hydroxy-3-oxo-1-aryl-1H,3H-isoindoles in liquid ammonia. A "one-pot" or two-step synthesis is described and a mechanism is proposed.
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■ Studies in the Field of Pyridazine Compounds, 28. Synthesis of 5-Substituted 6(5H)-1,2,4-Triazolo[4,3-b]pyridazinones
Judit Kosáry
*Department of Chemistry and Biochemistry and the University for Horticulture and Food Industry, Budapest, P.O.Box 53, H-1502, Hungary
Abstract
The unknown 5-hydroxy-6(5H)-1,2,4-triazolo[4,3-b]pyridazinones (4) were prepared by rearrangement of 6-hydroxyalkoxy-1,2,4-triazolo[4,3-b]pyridazines (1) in polyphosphoric acid. The reaction was accompanied by the formation of bis(triazolopyrydazine) derivatives (2). The products (4) were transformed to chloro derivatives (5).
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■ A New Heterocyclic Ring System: Synthesis of Pyrazolo[3’,4’:4,5]pyrimido[2,1-a]phthalazine Derivatives
Maria Santagati, Andrea Santagati, Maria Modica, and Filippo Russo*
*Istituto di Chimica Farmaceutica e Tossicologica, Università di Catania, Viale A. Doria 6, Catania, Italy
Abstract
Derivatives (5-7) of a new heterocyclic system containing the pyrimido[2,1-a]phthalazine skeleton were obtained by condensation of phthalic anhydride with the appropriate hydrazides (2-4). Moreover the preparation of 9-substituted 1H-pyrazolo[3’,4’:4,5]pyrimido[2,1-a][1,2,4]triazolo[4,3-c]phthalazin-12-ones (20) and (21) is described.
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■ Synthesis of 2-Amino-4-(4-pyridinyl)-1,3,5-triazine and Its Novel Reaction with Isocyanates
Baldev Singh
*Department of Medicinal Chemistry, Sterling Winthrop Pharmaceuticals Research Division, Rensselaer, NY 12144, U.S.A.
Abstract
The reaction of the sodium salt of 2-amino-4-(4-pyridinyl)-1,3,5-triazine (4) with t-butyl, isopropyl, phenyl, and p-chlorophenyl isocyanates formed the corresponding N-(alkyl or aryl)-2-amino-4-(4-pyridinyl)-1,3,5-triazines (6) whereas the reaction with methyl isocyanate and propyl isocyanate formed the expected N-alkyl-N’-[4-(4-pyridinyl)-1,3,5-triazin-2-yl]ureas (7).
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■ Regioselective O-Demethylation of Bisbenzylisoquinoline Alkaloids
Jun-ichi Kunitomo,* Megumi Oshikata, Michinori Akasu, and Hisashi Ishii
*Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo, 663, Japan
Abstract
The cleavage of methyl ethers of several bisbenzylisoquinoline alkaloids was studied and regioselective O-demethylation was observed.
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■ Diastereoselective Reduction of Derivatives of 3,4-Dihydro-1-methylidene-2-tartaroylisoquinoline
Zbigniew Czarnocki, David B. MacLean, and Walter A. Szarek
*Department of Chemistry, McMaster University, Hamilton, Ontario, Canada L8S 4M1
Abstract
Various enamides were prepared from 3,4-dihydro-6,7-dimethoxy-1-methylisoquinoline by reaction with (R,R)-tartaric acid derivatives. The enamides were reduced with hydrogen over a platinum catalyst to afford diastereomeric mixtures enriched in the (1R)-isomer. The diastereoselectivity of the reduction step was assessed by conversion of the mixtures into N-acetylsalsolidine and measurement of its specific rotation. The enamide (5c), in which the hydroxyl groups of the 2-tartaroyl group are unprotected, cyclizes to an aminal (9) in the presence of acids. The reduction of 5c with sodium borohydride in acidic media afforded a diastereomeric mixture enriched in the (1S)-isomer.
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■ C-Nucleosides. 19. Synthesis of 7- and 8-Substituted 4-[1-(β-D-Ribofuranosyl)oxo]-1,3-dihydro-2H-1,5-benzodiazepin-2-one
Yasutaka Ito, Masakazu Wakimura, C. Ito, and Isamu Maeba*
*Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya 468, Japan
Abstract
The synthesis of 7- and 8-substituted 4-[1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)oxo]-1,3-dihydro-2H-1,5-benzodiazepin-2-one from furanone glycoside (1) is described. Treatment of 1,2-diamino-4-substituted benzenes (2a-c) with 1 gave a mixture of 7- and 8-substituted 4-[1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)oxo]-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one (3a-d). Dehydrogenation of 3a-d with DDQ and a trace of PTSA afforded 7- and 8-substituted 4-[1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)oxo]-1,3-dihydro-2H-1,5-benzodiazepin-2-ones (4a-f). The position of the substituent in compounds (4a-f) was confirmed by 1H- 13C long-range COSY and NOE experiments with the corresponding N1-methyl derivatives (5a-c). Deprotection of compounds (4a-e) with methanolic sodium hydroxide afforded 4g-k.
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■ Application of Photoamination to Synthesis of Benzylisoquinolines, Aporphins, and Isopavines
Masahide Yasuda,* Shuichi Hamasuna, Katsuhiko Yamano, Jun-ichi Kubo, and Kensuke Shima
*Department of Industrial Chemistry, Faculty of Engineering, Miyazaki University, Gakuen-Kibanadai, Miyazaki 889-21, Japan
Abstract
The preparation of benzylisoquinolines, isopavines, and aporphines was performed by the photoamination of stilbene, p-methoxystilbene, and phenanthrene with amino alcohols, aminoacetal, allylamine in the presence of dicyanobenzene followed by the cyclization with BF3 or CF3SO3H.
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■ A Route to 1-Azaspirans Related to Perhydrohistrionicotoxin
Charles M. Thompson
*Department of Chemistry, Loyola University of Chicago, Chicago, Illinois 60626, U.S.A.
Abstract
Described herein is a brief synthetic approach to 1-azaspirans. The key transformations in the sequence, starting from 2-cyclohexenone, employ a chelation-assisted regiochemical ring opening of an epoxide and the Lewis acid promoted, bishomoenolate dianion addition to a [substituted] cyclohexyl-N-benzylimine.
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■ Synthesis of 1,2,3,4-Tetrahydroacridine and 5,6,7,8-Tetrahydroquinoline Derivatives as Potential Acetylcholinesterase Inhibitors
Franco Gatta,* Maria Rosaria Del Giudice, Massimo Pomponi, and Maurizio Marta
*Laboratorio di Chimica del Farmaco, Istituto Superiore di Sanita, Viale Regina Elena, 299-00161 Roma, Italy
Abstract
This paper describes the synthesis of 1,3,4,5-tetrahydropyrazolo[3,4,5-kl]acridine (2) and 11-amino-1,3,4,5-tetrahydroazepino[3,2-b]quinolin-2-one (3) obtained by Schmidt reaction of 9-amino-3,4-dihydroacridin-1(2H)-one (1) and the preparation of 4,5-dihydro-3H-isoxazolo[3,4,5-kl]acridine (7) obtained in the same manner starting from 3,4-dihydroacridine-1,9(2H,10H)-dione (6). The corresponding pyrazolo[3,4,5-de]quinoline (20) and isoxazolo[5,4,3-de]quinoline (18) are also reported. The compounds have been prepared with the aim of studying their possible activity as acetylcholinesterase inhibitors.
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■ Triazolopyridines. 13. Reaction between Triazolopyridinium Ylides and Electrophiles
Belen Abarca,* Rafael Ballesteros, Mohamed R. Metni, Gurnos Jones,* David J. Ando, and Michael B. Hursthouse
*Departamento de Quimica Orgánica, Facultad de Farmaica, Universitat de Valencia, Avda. Blasco Ibañez, 46100 Valencia, Spain
Abstract
The triazolopyridinium ylides (4) are protonated and react with acylium and nitronium ions at the end of the side chain, giving acyl derivatives (8a, 8b) and dinitro derivatives (10a-10c). The structure of the dinitro compound (10b) is confirmed by X-ray diffraction.
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■ Synthesis of 4-, 5-, 6- and 7-Substituted N-Tosylindoles from Substituted Anilines
Yasushi Murai, Shougo Kobayashi, Seiichi Inoue,* and Kikumasa Sato
*Department of Applied Chemistry, Faculty of Engineering, Yokohama National University, Tokiwadai, Hodogaya-ku, Yokohama 240, Japan
Abstract
4-, 5-, 6-, and 7-Substituted N-tosylindoles are prepared from N-tosylanilides, carrying 2-acetoxy-1-(isopropylthio)ethyl group at the ortho position, which can be prepared from substituted anilines and dialkyl sulfide by [2,3] sigmatropic rearrangement.
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■ Directed Lithiation of 1-(tert-Butoxycarbonyl)indolines. A Convenient Route to 7-Substituted Indolines
Masatomo Iwao* and Tsukasa Kuraishi
*Department of Chemistry, Faculty of Liberal Arts, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852, Japan
Abstract
1-(tert-Butoxycarbonyl)indolines were regioselectively lithiated at 7-position with s-BuLi-TMEDA in ether or THF at -78 °C. The lithiated species were reacted with a range of electrophiles to give 7-substituted indoline derivatives.
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■ Study of the Reaction of Several Ketone Enolates with 3-Iodobenzo[b]thiophene under Thermally Initiated SRN1 Reaction Conditions
Montserrat Prats,* Carmen Gálvez, and Lluís Beltran
*Departament de Química Orgànica, Universitat de Barcelona, Martí i Franquès, 1-11, 08028 Barcelona, Spain
Abstract
The reaction of 3-iodobenzo[b]thiophene (1) with the potassium enolates of cyclohexanone (2a), acetone (2b), and acetophenone (2c) in DMSO for 1 h at room temperature in the dark, gave the desired α-hetaryl ketones (3a-c) in low yield. The thermally activated SRN1 reaction with the ion enolate (2a) was studied in more detail and it was found that the radical chain SRN1 mechanism could compete with one of ionic character.
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■ Convenient Synthesis of 5-Trifluoromethyl-3-oxazolines and 5-Trifluoromethyloxazoles
Yasuhiro Kamitori, Masaru Hojo,* Ryoichi Masuda, Toshiya Takahashi, and Masaaki Wada
*Department of Industrial Chemistry, Faculty of Engineering, Kobe University, Kobe 657, Japan
Abstract
Aldehyde tert-butyl(methyl)hydrazones were acylated with trifluoroacetic anhydride to afford 3-tert-butyl(methyl)hydrazono-1,1,1-trifluoroalkan-2-ones (4) in good yields. Several 5-hydroxy-5-trifluoromethyl-3-oxazolines (5) were successfully synthesized by thermally induced reaction of 4 adsorbed on silica gel. Treatment of 5 with POCl3/pyridine and subsequent dehydrochlorination with diisopropylethylamine gave 5-trifluoromethyloxazoles (6) in high yields.
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■ Synthesis of 2,3-Fused Quinolines from 3-Substituted Quinoline 1-Oxides. Part 1.
Yutaka Miura,* Sakae Takaku, Yasuo Fujimura, and Masatomo Hamana
*Exploratory Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotenba, Shizuoka 412, Japan
Abstract
3-(2-Bromoethyltosylamino)quinoline 1-oxide (4) reacted with TsCl-NH4OH and TsCl-K2CO3 to afford the 2-aminoquinoline (5) and the 2-quinolinone (8). Cyclization of 5 and 8 under basic conditions gave the piperazino-quinoline (6) and the morpholino-quinoline (9). Similar reactions of 3-(2-bromoethoxy)quinoline 1-oxide (13) in the presence of TsCl gave also the 2-aminoquinoline (14) and the 2-hydroxyquinoline (16), but accompanied with fair amounts of by-products (15 and, 15 and 17). Cyclization of 14 and 16 gave the morpholino-quinoline (18) and the 1,4-dioxano-quinoline (19) in somewhat lower yields.