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. 48, No. 6, 1998
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■ Facile in situ Preparation of o-Azaxylylene from N,O-Diethoxycarbonyl-o-aminobenzyl Alcohol
Kota Nishiyama, Hajime Kubo,* Tomohide Sato, Kimio Higashiyama, and Shigeru Ohmiya
*Department of Synthetic Organic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
o-Azaxylylenes were generated only by gentle refluxing of N,O-diethoxycarbonyl-o-aminobenzyl alcohols in o-dichlorobenzene and then underwent the Diels-Alder reaction with dienophiles to give 1,2,3,4-tetrahydroquinolines.
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■ Merckonine, a New Aconitine-Type Norditerpenoid Alkaloid with a -N=C-19H Functionality
Haridutt K. Desai, L. Phillip Silverman, and S. William Pelletier*
*Institute for Natural Products Research and Department of Chemistry, Chemistry Building, The University of Georgia, Chemistry Building, AthensGeorgia 30602-2556, U.S.A.
Abstract
From a commercial source of aconitine, "Aconitine Potent Merck", isolated from Aconitum napellus L., Lot No. 30169, a new minor norditerpenoid alkaloid, "merckonine" has been isolated. Structure (1) for the new alkaloid was assigned on the basis of its physical and spectroscopic data and synthesis from aconitine. The known alkaloids 3-deoxyaconitine, aconitine and mesaconitine were also isolated in pure form from this commercial source.
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■ Regioselective Nucleophilic Substitution of Halogen Derivatives of 1-Substituted 4-Oxo-1,4-dihydroquinoline-3-carboxylic Acids
István Hermecz,* Lelle Vasvári-Debreczy, Benjamin Podányi, Géza Kereszturi, Mária Balogh, Ágnes Horváth, and Péter Várkonyi
*CHINOIN Pharmaceutical and Chemical Works Ltd., P. O. Box 110, H-1325 Budapest, Hungary
Abstract
The rate of the nucleophilic displacement of the fluoro atom of 7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate could be enhanced either by the introduction of further fluoro atom(s) into position(s) 6 and/or 8, or by the formation of a boron chelate (e.g. 3). The regioselectivity of the nucleophilic substitution of the chloro atom in 1-substituted 6-fluoro-7-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids could also be enhanced by the formation of a boron chelate (e.g. 7).
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■ Syntheses of 1-Hydroxytryptamines and Serotonins Having Fattyacyl or (E)-3-Phenylpropenoyl Derivatives as an Nb-Substituent, and a Novel Homologation on the 3-Substituent of the 1-Hydroxytryptamines upon Treatment with Diazomethane
Masanori Somei,* Harunobu Morikawa, Koji Yamada, and Fumio Yamada
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
1-Hydorxytryptamines (6a-f) having (E)-3-phenyl-, (E)-3-(4-hydroxyphenyl)-, (E)-3-(4-hydroxy-3-methoxyphenyl)propenoyl, octanoyl, hexadecanoyl, and docosanoyl group as a Nb-substituent are prepared for the first time. Preparations of serotonins (2a-c, e) from the corresponding 1-hydroxytryptamines (6a-c, e) are also reported. A novel homologation on the 3-substituent of 1-hydroxytryptamines is discovered upon treatment with diazomethane in chloroform or dichloromethane.
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■ Synthesis of 2-Alkylidene-3,3-dialkyl-1,4-dithianes and Their Oxathiane Analogues by 1,2-Sulphur Migration
M. Teresa Barros, Christopher D. Maycock,* and Lúcia S. Santos
*Instituto de Tecnologia Quimica e Biologia, Universidade Nova de Lisboa, Rua da Quinta Grande 6, 2780 Oeiras, Portugal
Abstract
2-Alkylidene-3,3-dialkyl-1,4-dithianes and their oxathiane analogues were prepared from 1,2-diketones by a process involving formation of the monodithioacetal, transformation to a tertiary alcohol with organometallic reagents and ultimately 1,2-sulphur migration using methanesulphonyl chloride in pyridine as the activating agent.
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■ Synthesis of 5-Substituted Indole Derivatives, I. An Improved Method for the Synthesis of Sumatriptan
Béla Pete, István Bitter, Csaba Szántay, Jr., István Schön, and László Töke*
*Department of Organic Chemical Technology, Technical University Budapest, H-1521 Budapest, Gellért tér 4, Hungary
Abstract
An improved synthesis of sumatriptan (1b) via Fischer cyclization was achieved by introducing the ethoxycarbonyl group on the N-atom of the sulphonamide moiety in N-methyl-4-hydrazinobenzenemethanesulphonamide (7). As a result, substitution on the benzylic carbon of the indole nucleus could be avoided; however, formation of 1,1-bis-(indol-2-yl)-4-dimethylaminobutane-type by-product (19) was observed. The indolization procedure was optimized to suppress the unwanted side reaction. The N-protection of the sulphonamide moiety was found to be beneficial regarding the purification of the 3-[2-(dimethylamino)ethyl]-N-ethoxycarbonyl-N-methyl-1H-indole-5-methanesulphonamide (18).
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■ Electrochemistry of 7-Carboethoxycycloheptatriene and Its Aza-analogues: Ring Contruction of Azepine Derivatives to AnilineDerivatives by Oxidation and N—N Bond Rupture of Diazepine Derivatives to 1-Amino-4-cyano-1,3-butadiene Derivatives by Reduction
Satoru Kondo, Hiroshi Suzuki, Tatsuya Hattori, Takayasu Ido, and Katsuhiro Saito*
*Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
Abstract
Electrochemical reduction or oxidation of 7-ethoxycarbonylcycloheptariene afforded 2-ethoxycarbonylcycloheptatriene and ethyl phenylacetate, respectively. N-Alkoxycarbonyl-1H-azepine formed N-alkoxycabonylaniline in electrochemcial oxidation via a ring contruction. N-Alkoxycarbonyl-1H-1,2-diazepine afforded N-alkoxycarbonyl-1-amino-4-cyano-1,3-butadiene in electrochemical reduction via an N-N bond fission.
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■ Synthesis of Thieno[2,3-d]pyrimidines and Aminopyrimidines from 2-Alkoxy-5-cyano-4-thioxopyrimidine Intermediates
Matthias Rehwald* and Karl Gewald
*Department of Organic Chemistry, Technical University of Dresden, Mommsenstrasse 13, D-01062 Dresden, Germany
Abstract
β-Chloro-α-cyanocinnamonitrile reacts in an one-pot reaction with potassium thiocyanate and alkanol to form 2-alkoxy-6-phenyl-5-cyano-1,4-dihydro-4-pyrimidinthiones. The products were S-alkylated to yield thieno[2,3-d]pyrimidines on cyclization and aminopyrimidines on substitution of alkoxy and alkylthio groups.
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■ Electron Impact Induced Fragmentation of 4-Aryl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-diones
Klaus K. Mayer,* Stefan Dove,* Herwig Pongratz, Mevlüt Ertan, and Wolfgang Wiegrebe
*Pharmazeutische Chemie I, Institut für Pharmazie, Universität Regensburg, Universitätsstraße 31, D-93040 Regensburg, Germany
Abstract
The molecular ions (M+·) of 4-substituted aryl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-diones (Biginelli compounds) (2-18) decompose by loss of the substituents X of the phenyl group (X = o-F; o-, m-, p-Cl, Br, OCH3,CH3; 2,3-, 2,4-, 2,6-, 3,4-dichloro) giving rise to prominent (M - ·X)+ ions at 70 and 12 eV, respectively. In the cases of o-Cl and o-Br substitution, the M+· is extremely unstable. In general, metastable M+· (1st ffr) eliminates preferably H·, that of 15 (2,6-dichloro), however, exclusibely a chlorine atom. As corroborated by 2H-labelling, reversible H-migration from C-4 to the phenyl group takes place (1, 1a-1c). The collisional activation spectra of the (M· - X)+ ions of 3 (o-Cl) and 6 (o-Br) are identical but different from the indistinguishable spectra of the (M - ·X)+ ions of 4 (m-Cl), 5 (p-Cl), 9 (o-OCH3), 11 (p-OCH3), and 14 (p-CH3). Semiempirical MO calculations (MOPAC 6.0, PM 3 Hamiltonian) of the M+· of all ortho-substituted derivatives support a close interaction of o-Cl and o-Br with the carbonyl oxygen, leading to elimination of these substituents and affording cyclic oxonium ions. In th other cases loss of X· is explained as a consequence of 4-H migration to the phenyl group.
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■ A Novel Synthesis of 1,6-Diamino-2-pyridones and [1,2,4]Triazolo-[1,5-a]pyridine Derivatives
Yoichi Yamada,* Heinosuke Yasuda, and Akiko Takayama
*Department of Chemistry, Faculty of Education, Utsunomiya University, 350 Mine, Utsunomiya 321-8505, Japan
Abstract
3-Cyano-1,6-diamino-2-pyridone derivatives (3) posessing various alkoxycarbonyl groups are prepared directly from the reaction of dialkyl (E)-2,3-dicyanobutendioates (1) with cyanoacetohydrazide (2). The resulting diamine (3) (R = Et) is readily cyclized to 2-substituted [1,2,4]triazolo[1,5-a]pridine derivatives (5) in high yields by treatment with orthocarboxylic esters (4) such as trimethyl orthoformate or triethyl orthoacetate etc. Furthermore, 3-cyano-6-amino-2-pyridones (6) are although abtained in excellent yields by the reductive deamination of 3. The structural study of 6 was carried out by spectroscopic methods in some details.
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■ Preparative Scale Conversion of D-Xylose into Hydrophilically Functionalized Pyrazoles
Volker Diehl, Eckehard Cuny, and Frieder W. Lichtenthaler*
*Institut für Organische Chemie, Technische Universität Darmstadt, Petersenstr. 22, D-64287 Darmstadt, Germany
Abstract
An expeditious, 4-step procedure is described for the conversion of bulk-scale accessible D-xylose into 5-hydroxymethyl-1-phenylpyrazole-3-carboxaldehyde (3), which, in turn, is converted into various pyrazole building blocks with versatile application profiles, such as the 1-phenylpyrazole-3,5-dicarboxylic acid (9), the respective 3,5-dialdehyde (10), and 3,5-bis(aminomethyl)-1-phenylpyrazole (13).
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■ Synthesis of Pluriaminated Pyridines
Angela De Munno,* Vincenzo Bertini, Nevio Picci, Francesca Iemma, and Marco Pocci
*Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgnimento 35, I-56126 Pisa, Italy
Abstract
The key reagent 3,5-dichloro-4-pyridinecarbonitrile (1) was used to synthesize 4-aminomethylpyridine derivatives 3,5-disubstituted with various amino groups, very active as inhibitors of diamine oxidase. The study of the reaction allowed to discover conditions for the gradual substitution in good yields of the two chlorine atoms to give symmetrically and unsymmetrically disubstituted derivatives (3), or the substitution of the cyano group, or the formation of amidines. The reduction of the cyano to aminomethyl group in compounds (3) afforded the target bioactive products.
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■ Alternative Synthesis of (-)-Malyngolide Utilizing (-)-Quinic Acid
Keizo Matsuo,* Takuya Matsumoto, and Keiji Nishiwaki
*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan
Abstract
(-)-Malyngolide, an antibiotic isolated from a blue-green algae, was synthesized starting from (-)-quinic acid.
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■ Synthesis of Pyrazolo[4,3-c]quinoline-5-oxide by Reductive Cyclization of 4-Acetyl-5-(2-nitrophenyl)pyrazole: Revision of the Reported Structures
Genadiy D. Kalayanov and Joong-Kwon Choi*
*Korea Research Institute of Chemical Technology, P.O. Box 107, Yousung, Taejeon, 305-600, Korea
Abstract
Cyclocondensation of 3-(2-nitrobenzoyl)pentane-2,4-dione with phenylhydrazine provided 4-(2-nitrobenzoyl)-3,5-dimethyl-1-phenylpyrazole (5) instead of 4-acetyl-3-methyl-5-(2-nitrophenyl)-1-phenylpyrazole (2). Catalytic hydrogenation of 2 resulted in the stepwise formation of 3,4-dimethyl-1-phenylpyrazolo[4,3-c]quinoline-5-oxide (3), 3,4-dimethyl-1-phenyl-1H-pyrazolo[4,3-c]quinoline (12), and 3,4-dimethyl-1-phenyl-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (13). Alternate routes for reduction of 5 under different conditions and a facile synthesis of 2 are also described.
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■ Pyrrolo[2,3-d][1,2,3]triazoles as Potential Antineoplastic Agents
Alessandra Passannanti, Patrizia Diana, Paola Barraja, Francesco Mingoia, Antonino Lauria, and Girolamo Cirrincione*
*Instituto Farmacochimico, Università Degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy
Abstract
Halonitropyrrole (1a) underwent nucleophilic substitution by substituted benzylamines (7) to give the intermediates (8), which by reduction and diazotization followed by an intramolecular coupling reaction led to derivatives of the title ring system (10).
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■ New Efficient Synthesis of Ethyl 2,3-Cycloalkenopyridine-4-carboxylate
Ha Young Kim, Sung Hoon Kim, Ghilsoo Nam, Hyenjoo Son, Tae Jo Park, Sook Ja Lee, Jahyo Kang, Dae Yoon Chi,* and Joong Hyup Kim*
*Biochemicals Reserach Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 131-650, Korea
Abstract
Ethyl 2,3-cycloalkenopyridine-4-carboxylates (6a-c) from 2-chlorocycloalkanone and ethyl cyanoacetate have been synthesized in 4 steps with overall 68, 68, 25% isolation yield for cyclopenteno (6a), cyclohexeno (6b) and cyclohepteno (6c) derivatives, respectively. Pyridine ring is constructed from 1,5-dicarbonyl precursor and nitrogen source. In order to prepare 1,5-dicarbonyl precursor, malonic ester synthesis is used. Alkylation of 2-chlorocycloalkanone (1a-c) with ethyl cyanoacetate affords ethyl cyano-(2-oxocycloalkanoyl)acetate (3a-c). Second alkylation of 3a-c with allyl bromide gives ethyl 2-cyano-2-(2-oxocycloalkanoyl)-4-pentenoate (4a-c). Ozonolysis of olefins (4a-c), and continuously pyridine ring formation with hydroxylamine provides ethyl 2,3-cycloalkenopyridine-4-carboxylate N-oxide (7a-c). This N-oxide is easily reduced with phosphorous trichloride in chloroform. Replacement of hydroxylamine hydrochloride by ammonium foramte as a nitrogen source reduced one step in this process, directly forming 2,3-cycloalkenopyridine-4-carboxylate.
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■ Hydrolysis of 4-Amino-3-qunolinesulfonamides
Leszek Skrzypek
*Department of Organic Chemistry, The Medical University of Silesia, Jagiellonska Str. 4, 41-200 Sosnowiec, Poland
Abstract
Acid hydrolysis of 4-amino-3-quinolinesulfonamides (3) gives 1,4-dihydro-4-oxo-3-quinolinesulfonamides (4), 4-aminoquinolines (5) or a mixture of these compounds.
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■ Recent Advances in Selective Syntheses of 6- and 7-Substituted Pteridines
Shizuaki Murata,* Kenji Kiguchi, and Takashi Sugimoto
*Human Informatics, Graduate of School, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan
Abstract
Novel regioselective methods for construction of biologically important pteridines which contain carbon substitution on the 6- or 7-position using pteridine ring-forming cyclocondensations, nucleophilic substitution reactions, and radical reactions are reviewed.
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■ Acid-catalysed C-3 Epimerization of Reserpine and Other Indolo-[2,3-a]quinolizidines
Mauri Lounasmaa,* Mathias Berner, and Arto Tolvanen
*Laboratory for Organic and Bioorganic Chemistry, Technical University of Helsinki, P.O. Box 6100, FIN-02150 HUT Espoo, Finland
Abstract
The acid-catalysed C-3 epimerization of the indole alkaloid reserpine (1) and other closely related indolo[2,3-a]quinolizidines is reviewed. The three mechanisms that have been proposed and relevant experimental findings are discussed. Representative examples of C-3 epimerization reactions are included.