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. 26, No. 3, 1987
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■ Synthesis of 5-Substituted Pyrimidines through ortho-Directed Lithiation Reactions
Akimori Wada, Junpei Yamamoto, and Shoichi Kanatomo
*School of Pharmacy, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan
Abstract
Treatment of 2- and/or 4-substituted pyrimidine with LiTMP in ether at 0°C, followed by quenching with various electrophiles afforded the corresponding 5-substituted pyrimidines.
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■ New Secocularine Alkaloids from Sarcapnos Species
Luis Castedo, Domingo Domínguez, Susana López, Emilia Tojo, and Carmen Villaverde
*Departmento de Química Orgánica, Facultad de Química y Sección de Alcaloides, Universidad de Santiago de Compostela, E-15706, Santiago de Compostela, Spain
Abstract
Five new secocularine alkaloids have been isolated from Sarcocapnos species and their structures elucidated by spectroscopic studies and chemical correlations.
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■ Synthesis of Sequiterpene Alkaloids, Guaipyridine, Epiguaipyridine, and Related Compounds
Teruyo Okatani, Junko Koyama, Kiyoshi Tagahara, and Yukio Suzuta
*Kobe Women’s College of Pharmacy, Motoyamakita, Higashinad, Kobe, Hyogo 658, Japan
Abstract
Synthesis of sesquiterpene alkaloids. guaipyridine, epiguaipyridine and related compounds. was accomplished by application of Diles-Alder reaction of 1,2,3-triazine with enamines.
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■ Four New Dimeric Monoterpene Alkaloids from Scaevola racemigera Däniker (Goodeniaceae)
Alexios-Leandros Skaltsounis, François Tillequin, Michel Koch, Jacques Pusset, and Gerard Chauvière
*U.A. au C.N.R.S.n°484, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, 4, Avenue de l’Observatoire, F-75006 Paris, France
Abstract
Four new dimeric monoterpene alkaloids (1-4) have been isolated from the aerial parts of Scaevola racemigera Däniker. Their structures have been elucidated by spectroscopic studies and chemical correlations.
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■ The Formation and X-Ray Crystal Structure of a Novel Bridged Dilactone Derived from Chrysanthemic Acid by Dimerization of Lavandulylic Acids
Zeev Goldschmidt, Bernard Crammer, and Hugo E. Gottlieb
*Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel
Abstract
Thermal acid catalysed rearrangement of chrysanthemic acid or its ethyl ester afforded 5,8-[1-(2-methylpropyl)]-ethano-3,3,8- trimethyl-5-(2-methylethyl)-3,4,4a,5,8,8a-hexahydro-1H,6H-pyrano[3,4-c]- pyran-1,6-dione, the structure of which was confirmed by X-ray analysis.
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■ A Novel Preparation of Polarized Ethylenes by the Reaction of Thioamides or Dithiocarboxylates with Tetracyanoethylene Oxide. Synthesis of Pyrazoles and Pyrimides
Yoshinori Tominaga, Yoshiki Matsuoka, Shinya Kohra, and Akira Hosomi
*Center of Instrumental Analysis, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
Polarized ethylenes having both electrondonating (an amino or a methylthio group) and electronaccepting (two cyano groups) groups on the adjacent two olefinic carbon atoms were prepared by the reaction of thioamides or methyl dithiocarboxylates with tetracyanoethylene oxide in good yields. Reactions of these polarized ethylenes with hydrazine or guanidine carbonate gave the corresponding pyrazole and pyrimidine derivatives in good yields.
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■ Introduction of Functional Groups into the α-Position of N-Alkoxycarbonylpyrrolidines
Tatsuo Nagasaka, Hirohisa Tamano, Tomoaki Maekawa, and Fumiko Hamaguchi
*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
The reactions for the introduction of 0-, S-, N-, and C- functional groups into the α - position of N -alkoxycarbonylpyrrolidines using N-alkoxycarbonyl-α-ethoxypyrrolidines are described.
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■ Heteroanalogous Dezapurines via Novel 4+2 Cycloaddition Reactions of Ketenimines
Gert Kollenz, Gerhard Penn, Walter Ott, Karl Peters, Eva-Maria Peters, and Hans Georg von Schnering
*Isotope Department, Institut fur Organische Chemie, Karl-Franzens-Universitat Graz, Heinrichstr. 28, A-8010 Graz, Austria
Abstract
The heterocyclic 2,3-diones 1 and the ketenimines 2 combine yielding heteroanalogous deazapurines 4, 6 and 7 partly having so far unknown molecular skeletons, which were made evident with aid of X-ray structure analyses (6b,7a). IR- and 13C NMR measurements. The reaction pathways include 4+2 cycloaddition processes across the C=N-bond of the ketenimine, accompanied by several surprising rearrangements. These are the first examples observed of 4+2 cycloaddition reactions with ketenimines of to oxa-1,3-dienes.
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■ Synthesis of Novel Fluorine-containing Cephalosporins
Kiyoharu Nishide, Takeo Kobori, Daiei Tunemoto, and Kiyoshi Kondo
*Sagami Central Research Center, 4-4-1 Nishi-Ohnuma, Sagamihara, Kanagawa 229-0012, Japan
Abstract
Cephalosporins with (E)- and (Z)-7β-[2-(2-aminothiazol-4- yl)-4,4,4-trifluoro-2-butenamido] side chain were synthesized. Of these, the cephalosporin 12e having pyridiniomethyl group at the 3-position exhibited excellent activity against most of microorganisms tested.
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■ A New Synthetic Method of 6-Aryl- or Vinyl-substituted 2-Oxotetrahydro-1,3-oxazines
Takushi Kurihara, Tatsuya Terada, Yoshitaka Matsubara, and Ryuji Yoneda
*Faculty of Pharmaceutical Science, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
Abstract
A novel transformation of benzylic or allylic hydroxy-substituted N-tert-butoxycarbonyl compounds by treatment with methanesulfonyl chloride in the presence of triethylamine into 2-oxotetrahydro-1,3-oxazines is described.
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■ The Convergent AB+CD Route to 9-Acetyl-7,8,9,10-tetrahydronaphthacenedione
Krishanan Ravichandran, Donald J. Gosciniak, and Michael P. Cava
*Department of Chemistry, University of Alabama, Box 870336, University, Tuscaloosa, Alabama 35478-0336, U.S.A.
Abstract
The annelated sulfolene derivative (9) has been used as an “AB” synthon in a convergent AB + CD route to 9-acetyl-7,8, 9,10-tetrahydro-5,12-naphthacenedione (6), a key precursor to the highly deoxygenated anthracyclinone 4-demethoxy-6,11-dideoxydaunomycinane (5).
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■ Observations on the Reactions of Isocyanoacetane Esters with Isothiocyanates and Isocyanates
Daniel M. Solomon, Razia K. Rizvi, and James J. Kaminski
*Pharmaceutical Research Division, Schering-Plogh Research Institute, Bloomfield, NJ 07003, U.S.A.
Abstract
The reactions of the metal salts of α-isocyanoacetate esters with isothiocyanates and isccyanates were examined. The effects of modifying the reaction parameters on the outcome of the reaction (Schem I) of methyl α-isocyanoacetate (1a) with phenyl isothiocyanate (2a) have been studied, thus providing enhanced understanding of the factors controlling this useful process. Specifically, the substantial influence of reaction temperature and mode of addition of reagents on the yield of main product, thiazole 3a--as well as the novel observation of the formation of imidazole 4 as a minor, but reprducible and significant, side-product--has been documented. Previausly reported oxazole formation in the low-temprature reaction of the lithio derivative of 1 with phenyl isothiocyanate (2a) was not observed in the present study; only thiazole (3a) was detected under these conditions. The reaction of isocyano ester 1a with benzyl isothiocyanate (2b) gave thiazole ester 3b or the corresponding caboxylic acid; no imidazole product was isolatd, in contrast to the result obtained with penyl isothiocyanate (2a). The previously unreported reaction of the salt of an α-isocyanoacetate ester with an isocyanate was shown to produce an amino (alkoxycarbonyl) oxazole in low yield (not optimized). No correspoding hydroxy(alkoxycarbonyl)imidazole was deteded. (See Schemes IV and VII.)
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■ Synthetic Potential of Papaverine Derivatives via Benzynes
Angel Rodriguez de Lera, Santiago Aubourg, Rafael Suau, and Luis Castedo
*Departmento de Química Orgánica, Facultad de Química y Sección de Alcaloides, Universidad de Santiago de Compostela, E-15706, Santiago de Compostela, Spain
Abstract
When 6’-bromoderivatives of papaverine and papaveraldine were treated with dimsyl sodium, products which incorporate the reagent are obtained. Under similar conditions 6’-bromopapaverine methiodide afforded the expected aporphine skeleton.
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■ A New Rearrangement in the Methylation of 2-(Diethylamino)-3-(ethoxycarbonyl)-5-phenylazepinyl Anion
Johannis W. Streef, Henk C. van der Plas, Yun Y. Wei, Jean P. Declercq, and Maurice Van Meerssche
*Laboratory of Organic Chemistry, Agricultural University, De Dreijen 5, 6703 BC Wageningen, The Netherlands
Abstract
Treatment of the anion of 2-(diethylamino)-3-(ethoxycarbonyl)-5-phenyl-3H-azepine with methyl iodide leads to the formation of 2-(diethylamino)-7-(etholrycarbonyl)-7- methyl-3,4-dihydro, the structure of which was confirmed by an X-ray analysis of its picrate. The mechanism of this rearrangement reaction will be discussed.
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■ Transformations of 1,2,4-Thiadiazolo[2,3-x]azines
Bozidar Koren, Branko Stanovnik, and Miha Tisler
*Department of Chemistry, E. Kardelj University, Murnikova 6, 61000 Ljubljana, Slovenia
Abstract
Hydrolysis of 1,2,4-thiadiazolo/2,3-c/pyrimidine derivative 2 produced cyanoaminopyrimidine 4, while treatment of 1,2,4-thiadiazolo/2,3-b/ pyridazine 5 with hydrazine hydrate gave thiourea derivative 7. 1,2,4-Thiadiazolo/2,3-a/pyridine 8 and 1,2,4-thiadiazolo//2,3-a/pyrazine 9 gave by alkaline hydrolysis the corresponding pyridopyrimidine 10 and pteridine 11, respectively . The compound 10 was converted with phenacyl bromide into 14 and further cyclized in PPA into pyrido/2,3-d/ thiazolo/2,3-a/pyrimidine 15. Pyrazinylthiourea derivative 16 was cyclized in acidic solution into thiazolo/4,5-b/pyrazine 17, which was converted by hydrolysis and decaroxylation into amino derivative 20. This gave with ethyl acetoacetate pyrazino/2’,3’:4,5/thiazoIo/3,2-a/pyrimidine 23. 1,2,4-Thiadiazoloazines 24 and N-ethoxycarbonyl-N ’-azinylthioureas 25 were transformed with hydrogen peroxide into urea derivatives 26.
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■ Synthesis and Spectroscopic Studies on Some New Substituted 2-Quinoxalinecarboxamides and Their N-Oxides
Salim S. Sabri, Mustafa M. El-Abadelah, and Bassam A. Al-Bitar
*Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan
Abstract
Series of new 2-(N-phenylcsrbamoyl)-3-methylquinoxaline 1,4-dioxides (I), monoxides (II,III) and their nonoxygenated analogues (IV), as well as the corresponding series lacking the C3 methyl(V-VIII) have been prepared, and their 1H-nmr spectral data analyzed. The C3-Me protons in the di-N-oxides (I) resonate at higher field (δ2.45-2.80) than in the corresponding non-oxygenated analogucs(IV) (δ=3.0). The observed upfield shift for the C3-Me protons in the di-N-oxides (I) is maximum when two methylene carbons would separate to the “interacting” phenyl and quinoxaline rings. A comparable trend is observed for the quinoxaline-1-oxides (II), whereas the isomeric 4-oxides (III) closely resemble the parent quinoxalines (IV). This behavior might be due to the predominance of the intramolecular H-bonded conformation (A) in the di-N-oxides (I) and the N-1-oxides (II). Comparative nmr study of compounds (V-VIII) is also noted.
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■ Synthesis of a Reduced Neoproaporphine
Leon Mandell, Carol Anne Wilson, Shenna Sinclair, and Frederick Joseph Heldrich
*Department of Chemistry, Emory University, 1521 Pierce Drive Atlanta, Georgia 30322, U.S.A.
Abstract
Hydrolysis of the Birch reduction pmduct from a 1-benzyltetrahydroisoquinoline, 8, affords a novel reduced neoproaporphine skeleton, 16. The formation of 16 is believed to proceed by initial formation of an intermediate bis-enone, 5, followed by an intramolecular Michael addition.
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■ The Synthesis of the Isoquinoline Alkaloid Calycotomine via Functionalization of Enamide Double Bonds
George R. Lenz
*Department of Chemistry, G. D. Searle & Company, 4901 Searle ParkwaySkokie, Illinois 60077, U.S.A.
Abstract
The novel alkaloid calycotanine, a 1-hydroxymethylenetetrahydroisoquinoline, has been synthesized from 1-methyl-3,4-dihydroisoquinoline via the 2-benzyloxycarbonyl enamide derivative. Oxidation of the enamide with osmim tetroxide results in bis-hydroxylation and ring opening to form hydroxyacetcphenone carbamates. Hydrogenation results in reclosure of the isoquinoline ring and further reduction yielding l-hydroxymethylenetetrahydroisoquinolines.
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■ Homolytic Alkoxycarbonylation Reactions in Two-phase Systems 3. Introduction of a Single Carboxylic Acid Ester Function into Cyano- or Alkoxycarbonyl Substituted N-Heteroaromatics
Gottfried Heinisch and Gerhard Lötsch
*Institut für Pharmazeutische Chemie, Universität Wien , Pharmaziezentrum, Althanstrasse, 14 A-1090 Wien, Austria
Abstract
Homolytic alkoxycarbonylatlon reactions with cyanopyridines 1a, 2a, 3a, alkyl pyridinecarboxylates 1b, 2b, 3b, 3c and ethyl 4-pyridazinecarboxylate 4 in presence of dichloromethane were studied. It is demonstrated that under these conditions multiple substitution in general is suppressed markedly. Thus, this experimentally simple procedure represents an efficient and versatile method for single-step preparations of slkyl cyanopyridinecarboxylates 7a, 8a, 9a, 10a. Furthermore,it provides convenient access to so far not available mixed esters 5b, 7b, 8b,10b,13, derived from 2,3-pyridine-, 2,4-pyridine-, 3,4- pyridine- and 4,5-pyridazinedicarbaxylic acid.
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■ A New Termal Decomposition of the Isoxazole Ring
Andreina Corsico Coda, Luigi De Gaudenzi, Giovanni Desimoni, Pier Paolo Righetti, and Gianfranco Tacconi
*Dipartamento di Chimica Organica, Università di Pavia, V. le Taramelli 10, 27100 Pavia, Italy
Abstract
The thermal decomposition of 5-methoxy-3-methyl-4-phenylazoisoxazole (1) was re-investigated. Cleavage in the presence of dipolarophiles gave methyl 5-methyl-2-phenyl-l,2,3-triazole-4-carboxylate (3) , which derives from a known rearrangement, and N-phenylmethoxycarbony1nitrilimine, which was trapped. The mechanism of the thermal decomposition is discussed.
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■ Synthesis of Diazepino-fused Heterocycles: Reactions with 4-Chlorobutyl Isocyanate
Ahmed Kamal, Narendra A. V. Reddy, and Prahlad B. Sattur
*Regional Research Laboratory, Hyderabad 500 007, India
Abstract
The reactlon of anthranilonitrile with 4-chlorobutyl isocyanate gives urea 3, which undergoes a double cyclization to form 2,3,4,5-tetrahydro[1,3]- diazepino[1,2-c]quinazolin-7(8H)-one, upon heating or treatment with a base. Similarly, the reaction of 2-hydroxybenzonitrile with 4-chlorobutyl isocyanate and upon cyclization affords 2,3,4,5-tetrahydro[1,3]diazepino[1,2-c][1,3]benzoxazin-7-one.
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■ 1,3-Dipolar Cycloaddition of N-Oxide with 2-Methylene-1,3-dithiane
Makoto Yamamoto, Tsuyoshi Suenaga, Kazuya Suzuki, Kiyoshi Naruchi, and Kazutoshi Yamada
*Department of Applied Chemistry, Faculty of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
1,3-Dipolar cycloaddition of nitrile oxides and nitrones with 2-methylene-1,3-dithiane gave 5-substituted isoxazolines and isoxazolidines in good yield. By treatment with mercuric chloride or NBS isoxazolidine (12) was converted to corresponding lactone (13) which was a precursor of β-amino acid.
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■ Structure of Mulberrofuran R, a Novel 2-Arylbenzofuran Derivative from the Cultivated Mulberry Tree (Morus lhou Koidz.)
Hideki Kohno, Kazuhiro Takaba, Toshio Fukai, and Taro Nomura
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
A novel 2-arylbenzofuran derivative, mulberrofuran R, was isolated from an ethyl acetate extract of the root bark of the cultivated mulberry tree (Roso, a cultivated variety of Morus lhou Koidz.). Its structure was shown to be 1, on the basis of spectral evidence. Mulberrofuran R is regarded biogenetically as a variation of a Diels-Alder type adduct of s chalcone derivative and a dehydroprenyl-2-arylbenzofuran derivative.
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■ Hydrogenation and Hydrosilylation of Quinoxaline by Homogeneous Rhodium Catalysts
Shizuaki Murata, Takashi Sugimoto, and Sadao Matsuura
*Graduate School of Environmental Studies, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan
Abstract
Hydrogenation of quinoxalines by a homogeneous rhodium catalyst gives tetrahydroquinoxalines. The catalytic process is applicable for hydrosilylation of quinoxalines. 2-Methylquinoxaline is asymmetrically hydrosilylated by a chiral catalyst.
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■ Synthesis and Cycloaddittion Rection of 2a,4,5-Triazabenz[cd]azulene Derivatives
Noritaka Abe and Atsuko Gomi
*Department of Chemistry, Faculty of Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan
Abstract
2a, 4,5-Triazabenz [cd] azulene derivatives derivatives (2) were synthesized by the reaction of 8-hydrazino-3-phenyl-1-azaazulenes (1) with triethyl orthoformate. 2-Chloro substituted compound (2b) was easily hydrolized on silica gel and gave (2-chloro-8-imino-3-phenyl-l-aza-1,8-dihydroazulen-l-yl)formaldehyde oxime. Reaction of 2a with dimethyl acetylenedicarboxylate gave dimethyl 1-phenyl-2a,5-diazabenz [cd]azulene-3,4-dicarboxylate and dimethyl (l-cyano-3-phenyl-1,8-dihydro-1-azaazulen- 8-ylideneamino)maleate.
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■ A Natural Abundance 17O NMR Investigation of Substituted 1-Mehtyl and 1-Phenyl-2-thiohydantions
David W. Boykin
*Department of Chemistry, Georgia State University, University Plaza, Atlanta, GA 30303, U.S.A.
Abstract
Natural abundance 170 nmr spectroscopic data for seventeen 1-methyl- and 1- phenyl-2-thiohydantoins obtained in acetonitrile are reported: the relationship of 170 chemical shift to structure is discussed.
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■ Some Recent Advances in the Chemistry of Imines, in Particular Cycloaddition Reactions
Jagir Singh Sandhu and Bir Sain
*Division of Drug and Pharmaceutical Chemistry, Regional Research Laboratory, Jorhat 785 006, Assam, India
Abstract
This articale summarizes recent advances in the chemistry of imines in general and cycloaddition reactions of 1-aze-l,3-butadienes, 2-aza-1,3-butadienes, 1,4-diaza- 1,3-butadienes and 2,3-diaza-1,3-butadienes in particular.