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. 6, 1994
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■ Generation and Trapping of a Sulfenyl Chloride from an Isothiazolone
Tirthankar Ghosh* and Steven K. Wolk
*Rohm and Haas Research Laboratories, 727 Norristown Road, Spring House, PA 19477, U.S.A
Abstract
We have investigated the reaction of HCl with 2-methylisothiazol-3-one (1). In the presence of HCl, at elevated temperatures, 1 exists in equilibrium with the ring opened sulfenyl chloride (4). The existence of 4 has been proven by trapping with norbornene and 1-octyne.
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■ A Study on Sonodynamic Therapy-Antitumor Effect of Novel Sonodynamic Compounds under Ultrasound
Toshio Suzuki,* Shinkou Kamada, Yasuo Yoshida, and Katsuo Unno
*Department of Pharmaceutical Sciences, Akita University Hospital, Hondo, Akita 010, Japan
Abstract
Diacetylhematoporphyrin-mitomycin C conjugate (diAc-Hp-MMC) (1) prepared by a condensation of diacetylhematoporphyrin with MMC in the presence of N,N-dimethylaminopyridine and dicyclohexylcarbodiimide, and two of the pyridocarbazole derivatives (8) and (9) were provided for sonodynamic compounds and these compounds were found to show excellent cell-killing effect, comparing to those of the known sonodynamic compound hematoporphyrin, Hp 2HCl (2), DiAc-Hp (3), Hp-Co (4), Hp-Fe (5), Acrinol (6) and MMC (7).
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■ A Synthesis of 1,3,5-Thiadiazepine Skeleton Derivatives: Benzimidazo[2,1-b][1,3,5]pyridothiadiazepine and Benzimidazo[2,1-b][1,3,5]benzothiadiazepine Derivatives
Byung-Woo Jin and Sung-Hye Cho*
*Department of Chemistry, College of Sciences, Chung-Ang University, Tong-Jak Gu, Seoul 156-756, Korea
Abstract
Pyrido and benzothiadiazepine derivatives have been successfully synthesized in good yields by the reaction of N-substituted thiourea (6) and N-substituted S-methylisothiourea (7) derivatives in the presence of DCC or potassium carbonate.
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■ Fluoride Ion Promoted Azomethine Ylid Generation from 1-Methyl-2-[methylthio(trimethylsilylmethylimino)methylimino]-1,2-dihydropyridine, a Synthetic Equivalent of Aminonitrile Ylid
Shinya Kohra* and Yoshinori Tominaga
*Department of Chemistry, Faculty of Liberal Arts, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
1-Methyl-2-[methylthio(trimethylsilylmethylimino)methylimino]-1,2-dihydropyridine (1), prepared from 2-amino-1-methylpyridinium iodide in 3 steps, reacted with carbonyl compounds in the presence of cesium fluoride in acetonitrile to give 2-(1-methyl-1,2-dihydropyridylidene)aminooxazoline derivatives (6) via the 1,3-dipolar cycloaddition. This reaction was the first example of reaction of aminonitrile ylid with the C=O double bond.
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■ Bifunctional Antitumor Agents: Pyrrolo[9,10]phenanthrenes as Intercalative Drug Delivery Vehicles
Graham B. Jones,* Jude E. Mathews, and W. Kenneth Banner
*Howard L. Hunter Laboratories, Department of Chemistry, Clemson University, Clemson, SC 29634-1905, U.S.A.
Abstract
The preparation of a pyrrolo[9,10]phenanthrene nucleus is described. The utility of the template as a potential DNA intercalating drug delivery system is demonstrated by synthesis of a derived bis chloroethylamine alkylating system.
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■ Syntheses of the 7-N-Oxides of 6-Mercaptopurine and 6-Methylthiopurine
Kazuo Ogawa, Taisuke Itaya, and Tozo Fujii*
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
6-Mercaptopurine 7-N-oxide (6) has been synthesized for the first time from 4,6-dichloro-5-nitropyrimidine (12) by following a "phenacylamine route" through the intermediates (8) and (9). Methylation of 9 and removal of the p-methoxybenzyl group provided 6-methylthiopurine 7-N-oxide (7).
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■ Cytotoxic 6-Substituted 5,6-Dihydro-2H-pyran-2-ones from a Brazilian Medicinal Plant, Chorisia crispiflora
Mamoru Matsuda, Yuichi Endo, Shinji Fushiya, Takeshi Endo, and Shigeo Nozoe*
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Three cytotoxic 6-substituted 5,6-dihydro-2H-pyran-2-ones (1-3) were isolated from a Brazilian medicinal plant, Chorisia crispiflora. 1 was identified as argentilactone, and the structures of two new compounds (2 and 3) were determined on the basis of the physicochemical properties.
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■ One-Step Synthesis and Enzyme Inhibiting Activities fo Pyrizinostatin Analogs
Kuniaki Tatsuta* and Masayuki Kitagawa
*School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
Pyrizinostatin analogs were synthesized from 2-methylfervenulone and a variety of methyl ketones in only one step and showed stronger enzyme inhibiting activities than pyrizinostatin itsel.
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■ Synthesis of an Optically Active 1-Azaspiro[4.4]non-8-en-7-one
Masazumi Ikeda,* Ken-ichiro Matsubayashi, Takayuki Imoto, Kaoru Kitao, Hiroyuki Ishibashi, and Tatsunori Sato
*Kyoto Pharmaceutical University, Misasagi-Shichonocho, Yamashina, Kyoto 607-8414, Japan
Abstract
The 1-azaspiro[4.4]one-8-en-7-one (7) and its (R)-9-(3,4-methylenedioxyphenyl)-substituted derivative (12) have been synthesized using an intramolecular aldol condensation of the pyrrolidine derivatives (6) and (11) as a key step.
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■ Synthesis of Azacarbazoles
Yves Blache, Olivier Chavignon, Marie E. Sinibaldi-Troin, Alain Gueiffier, Jean C. Teulade,* Yves Troin, and Jean C. Gramain
*Laboratoire de Chimie Organique Thérapeutique, Groupe de Recherche en Pharmacochimie, Faculté de Pharmacie, Université de Clermont I, 28, Place Henri Dunant, B.P. 38, 63001 Clermont-Ferrand Cedex, France
Abstract
Photocyclization of N-Benzylenaminone (7) led to azacarbolinones products which were fragmented to unexpected aldehydes (9) and (11).
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■ New Benzofuran-Type Antiarrhythmic Compounds Related to Propafenone
Gerhard Ecker, Wilhelm Fleischhacker,* and Cristian R. Noe
*Institute of Pharmaceutical Chemistry, University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria
Abstract
Synthesis of two benzofuran compounds (2a and 2b), which are structurally and - by their action as sodium channel blockers - also pharmacologically related to propafenone is described
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■ Alkyl Anhydronium Bases of Harmaline — A β-Carboline Alkaloid of Peganum harmala
Bina Shaheen Siddiqui,* Shahid Bader Usmani, Sabira Begum, and Salimuzzaman Siddiqui
*H. E. J. Postgraduate Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan
Abstract
This paper reports the synthesis of alkylanhydronium bases from harmaline on its reaction with different alkyl halides. There is no earlier procedure of formation of alkylharmaline with anhydronium skeleton, with these or any other reagent.
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■ Synthesis of 4-Substituted 11-Phenyl-1,2,3,4-tetrahydro-5H-azepino[3,4-b]quinolin-5-one Derivatives as Potential Peripheral Benzodiazepine-Receptor Ligands
Andrea Cappelli,* Maurizio Anzini, and Salvatore Vomero
*Dipartimento Farmaco Chimico Technlogico, Università degli Studidi Siena, Banchi di Sotto, 55 - 53100 Siena, Italy
Abstract
The synthesis of semirigid analogs of PK 11195, the highly specific peripheral benzodiazepine-receptor ligand, is reported. Compound (4) underwent the Wittig reaction with acetaldehyde to give olefin (7) which after allylic bromination was aminated to give the ω-amino esters (10a-c). These compounds were then hydrogenated and cyclized in boiling toluene with DMAP as catalyst. The standard procedure failed in the case of compound (10b), thus other cyclization procedures were examinated.
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■ Synthesis of 3-Alkynylpyridazines from 3-Trifluoromethanesulfonylpyridazines
Dominique Toussaint, Jean Suffert,* and Camille G. Wermuth
*Laboratoire de Pharmacochimie Moleculaire, (UPR 421 DU CNRS), Centre de Neurochimie du CNRS, 5, rue Blaise Pascal, 67084 Strasbourg-Cedex, France
Abstract
An efficient synthesis of 3-alkynylpyridaziens starting from the pyridazine triflates using a Pd° cross-coupling reaction is described.
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■ Three New Flavanone Derivatives from the Root Bark of Sorocea bonplandii Baillon
Irene Messana, Franco Ferrari, Franco Delle Monache, Rosendo A. Yunes,* and Eszter Gacs-Baitz
*Departamento de Quimica, Universidade Federale de Santa Catarina, Florianopolis, S.C. , Brazil
Abstract
Three new flavanone derivatives named sorocein C (2), sorocein D (1) and sorocein H (3) together with the known artonin D, kuwanon C, cyclomorusin, and kuwanon J were isolated from the methanolic extract of the roots of Sorocea bonplandii. The structures were assigned on the basis of spectroscopic evidences.
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■ A Synthesis of Heterocyclic Ring Systems. Pyrido[3‘,2‘:4,5]thieno[2,3-b]pyrrolizine and Pyrido[6‘,5‘:4,5][3‘,2‘:4,5]dithieno[2,3-b‘:2,3-b]dipyrrolizine
Carlos Peinador, Ma. Carment Veiga, Juan Vilar, and José Ma. Quintela*
*Departamento de Química Fundamental Industrial, Facultad de Ciencias, Universidad de La Coruña, Campus de A Zapateria, s/n, E-15071, La Coruña, Spain
Abstract
A synthesis for two new polycyclic heterocyclic ring systems is reported. Cyclization of pyrrolidinocarboxamide derivatives of ethyl 3-(pyrrol-1-yl)thieno[2,3-b]pyridine-2-carboxylate (4) and ethyl 3,5-di(pyrrol-1-yl)dithieno[3‘,2‘-e:2,3-b]pyridine-2,6-dicarboxylate (11) afford iminium salts that were transformed into the new heterocyclic compounds (6) and (13), respectively.
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■ Cycloaddition of Nitrile Oxides to 4-Oxobut-2-enoic Acid Derivatives
Francisco Fariña, M. Rosario Martín,* M. Victoria Martín, and Ana Martínez de Guereñu
*Departamento de Química Orgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, 28049-Madrid, Spain
Abstract
The 1,3-dipolar cycloadditions of aceto-, benzo- and bromoformonitrile oxides to cyclic and open-chain 4-oxobut-2-enoic acid derivatives have been investigated. The addition to 5-methoxyfuran-2(5H)-one (1) gave regioselectively 3-substituted 6-exo-methoxy-3a,6a-dihydrofuro[3,4-d]isoxazol-4(6H)-ones, whereas methyl (Z)- and (E)-4,4-dimethoxybut-2-enoates (2) and (3) afforded mixtures of regioisomeric isoxazolines.
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■ Synthesis and Amination of 4-Chloro-3-quinolinesulfonyl Chloride
Andrzej Maslankiewicz* and Leszek Skrzypek
*Department of Organic Chemistry, The Medical University of Silesia, Jagiellonska Str. 4, 41-200 Sosnowiec, Poland
Abstract
Chlorinolysis of 4-chloro-3-benzylthioquinoline (2) or thioquinanthrene (1) using chlorine gas in the presence of water gave 4-chloro-3-quinolinesulfonyl chloride (3). Amination of (3) performed in ether led to 4-chloro-3-quinolinesulfonamides (4). Reactions of compound (3) with an excess of primary or secondary amine in two phase (water/toluene or benzene) system gave 4-(substituted amino)-3-quinolinesulfonamides (5) with two identical amine rests. While 4-chloro-3-quinolinesulfonamides (4) were aminated with an excess of amine into aminosulfonamides (5) with two identical or two various amine rests.
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■ Ring-Chain Transformations of Semicyclic 3-Chloropropeniminium Salts to ω-Aminoalkyl-1,2-oxazoles Using Hydroxylamine
Jörg Bohrisch, Michael Pätzel, Jürgen Liebscher,* Peter G. Jones, and A. Chrapkowski
*Fachbereich Chemie, Humboldt-Universität Berlin, Hessische Strasse 1-2, D-10115 Berlin, Germany
Abstract
Semicyclic 3-chloropropeniminium salts (2) or (8) react with hydroxylamine giving either ω-aminoalkyl-1,2-oxazoles (4, 6, 10) by ring chain transformation or chlorovinyloximes (7) by ring opening
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■ Electrogeneration and Structural Discussion of 6-Benzyl-3,5-diphenylhydroxypyranones
Jose I. Lozano and Fructuoso Barba*
*Departamento de Química Orgánica, Universidad de Alcalá de Henares, 28871 Alcalá de Henares (Madrid), Spain
Abstract
The cathodic reduction of 2-chloro-2-phenylacetyl chloride in dichloromethanetetraethylammonium chloride on mercury cathode led to the formation of either a mixture of α- and γ-6-benzyl-3,5-diphenylhydroxypyranones or corresponding phenylacetate derivative of the latter depending on the conditions, in only one step. A study of these compounds solved the controversy which existed in the literature about the correct assignment of these structures.
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■ Application of the Mitsunobu Reaction in the Morphine Series. Preparation of 6β-Amino-14β-hydroxymorphine and 14-Hydroxycodeine Derivatives
Csaba Simon, Sándor Hosztafi, and Sándor Makleit*
*Department of Research, Alkaloida Chemical Co. Ltd., H-4440 Tiszavasvári, POB 1, Hungary
Abstract
By the application of the Mitsunobu reaction several 6β-phthalimido-14β-hydroxymorphine amd 14β-hydroxycodeine derivatives have been synthesized. Cleavage of the phthalimido derivatives with hydrazine hydrate afforded 6β-amino-14β-hydroxymorphine and 14β-hydroxycodeine derivatives. Catalytic hydrogenation of the Δ7,8 double bond offered a stereoselective way for the synthesis of the corresponding 6β-amino-14β-hydroxydihydrocoedine and 14β-hydroxydihydromorphine derivatives.
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■ 8-Piperazinyl-2,3-dihydro-1,4-dioxino[2,3-b]pyridine Derivatives: Synthesis and Interaction with 5-HT Serotonin Binding Sites
Benoît Joseph, Abdelhakim Benarab, and Gérald Guillaumet*
*Laboratoire de Chimie Bioorganique et Analytique, associe au CNRS, Université d‘Orléans, B.P. 6759, Rue de Chartres, 45067 Orleans Cedex 2, France
Abstract
The synthesis of 8-piperazinyl-2,3-dihydro-1,4-dioxino[2,3-b]pyridine derivatives (6a-c) are described. Their affinity and selectivity for 5-HT serotoninergic sites were evaluated.
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■ Synthesis of 2-Bnzamidoisoquinoline-1(2H)-one from 2-Vinylbenzoic Acid
Partha S. Ray* and Michael J. Manning
*Agricultural Chemical Group, FMC Corporation, P.O. Box 8, Princeton, New Jersey 08543, U.S.A.
Abstract
Treatment of N1-(2-vinylbenzoyl)-N2-benzoylhydrazine (2) with 3-chloroperoxybenzoic acid let to a cyclization of the intermediate epoxy derivative (3a) to give the alcohol (4a). Conversion of 4a to the thiocarbonate (5a) followed by a Chugaev type reaction gave the title compound (6).
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■ Selective Allylation and Propargylation of Azoles by Phase Transfer Catalysis in the Absence of Solvent
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
Phase transfer catalysis without solvent allows the selective preparation of N-allyl- and N-propargylazoles or N-(1-propenyl)- and N-(1,2-propadienyl) azoles by reaction of the parent azole with allyl or propargyl bromides. Small variations in the reaction conditions, base or temperature, afford the desired selectivity.
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■ Synthesis and Proton Nmr Spectra of the Monomethyl- and dimethylpyrimidine-5-carboxylic Acids. Regioselective Covalent Hydration at the 2- and 4-Ring Positions
Thomas J. Kress
*Chemical Process Research and Development Division, Lilly Reserach Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapaolis, IN 46285-4813, U.S.A.
Abstract
Pyrimidine-5-carboxylic acid, its 2-methyl-, 4-methyl, 2,4-dimethyl- and 4,6-dimethyl derivatives have been synthesized and their proton nmr spectra measured in dilute aqueous acid. Pyrimidine-5-carboxylic acid (1a, R2,4,6 =H) was found to afford an equilibrium mixture of covalent hydrates at both the 2- and 4-ring positions (2a and 3a). The 2-methyl derivative (1b, R2=me, R4,6=H) undergoes hydration exclusively at the 4-position (2b) while the 4-methyl derivative (1c, R2,6-=H, R4=Me) hydrates selectively at only the 2-position (3c). Convalent hydration was not observable for either the 2,4-dimethyl- (1d, R2,4=Me, R6=H) or 4,6-dimethyl- (1e, R2=H, R4,6=Me) pyrimidinecarboxylic acids. The synthetic routes to these substances are described and the degree of hydration for each compound was measured.
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■ Facile Synthesis of 4H,6H-Pyrrolo[3,4-c]isoxazoles
Hyung Jin Kiim and Jae Hyun Lee*
*Korea Research Institute of Chemical Technology, P.O.Box 9, Daedeog Danji, Daejoen 305-606, Korea
Abstract
Various 4H,6H-pyrrolo[3,4-c]isoxazoles (I) were prepared in good yields from the corresponding 4H,6H-furo[3,4-c]isoxazoles (II) by a ring cleavage and cyclization.
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■ Synthesis of Furan- and Pyrrole-containing α-Oligothiophenes via 1,4-Diketones
Liang-Huei Chen, Chin-Yu Wang, and Thung-Mei H. Luo*
*Department of Applied Chemistry, Chia Nan Junior College of Pharmacy, Tainan, 71710, Taiwan, R.O.C.
Abstract
Cyclization of the 1,4-dithienyl-1,4-diketones (3) by acid catalyst furnished the α-thienylfurans, whereas condensation with ammonium acetate provided the α-thienylpyrroles. The 2,5-bis[4-(2-thienyl)-1,4-butanedionyl]thiophene (5) similarly gave the first syntheses of 2,5-bis[2-(5,2‘-thienyl)pyrryl]thiophene (12) and 2,5-bis[2-(5,2‘-thienyl)furyl]thiophene (13).
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■ New Flavoid Glycosides of Helicteres angustifolia
Zong-Tsi Chen,* Shwu-Woan Lee, and Chiu-Ming Chen*
*Department of Applied Chemistry, Chia Nan Junior College of Pharmacy, Tainan, 71710, Taiwan, R.O.C.
Abstract
Two new flavonoid glycosides, takakin 8-O-β-D-glucuronide 6"-methyl ester (2), takakin 8-O-β-D-glucuronide 2"-sodium sulfate (3) together with a know flavonoid glycoside, takakin 8-O-β-D-glucuronide were isolated from the root bark of Helicteres angustifolia (Sterculiaceae). The structures of these compounds were established on the basis of spectroscopic and chemical evidence.
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■ Aminolysis of N-Acylpyrazoles
Choji Kashima,* Iwao Fukuchi, Katsumi Takahashi, and Akira Hosomi*
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
1-Acylpyrazoles reacted with amines having a tiny substituent to afford the corresponding amides. The aminolysis with bulky amines was controlled to be retarded by the steric factors. Due to this steric interaction, the stereoselective aminolysis was observed. This selectivity of aminolysis should increase the utility of pyrazoles as auxiliary compounds in the synthetic loop.
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■ Javacarboline, a New β-Carboline Alkaloid from the Stem of Picrasma javanica in Java
Kazuo Koike, Taichi Ohmoto,* Akira Uchida, and Isao Oonishi
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Javacarboline, a new β-carboline alkaloid was isolated from the stem of Picrasma javanica (Simaroubaceae). Its structure was elucidated at the extensive 1H and 13C nmr studies involving 1H-1H COSY, HSQC and HMBC experiments and X-ray diffraction analysis.