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. 24, No. 11, 1986
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■ A Convenient Preparation of Sulfinic Acids by the Reaction of 2-Sulfonylpyridines and Their N-Oxides with Nucleophiles
Naomichi Furukawa,* Masayuki Tsuruoka, and Hisashi Fujihara
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
Ipso-substitution reaction of 2-sulfonylpyridines and their N-oxides with alkoxide or thiolate anion afforded the sodium salts of sulfinic acids together with the corresponding substitution products in high yields. This procedure becomes a convenient and versatile method for preparation of various sulfinic acids.
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■ The Structural Study on 2-Aminodihydropyrimidine Derivatives
Yong Hae Kim* and Hyoung Rae Kim
*Department of Applied Chemistry, Korea Advanced Institute of Science and Technology, P.O.Box 150 Chong-Yang-ni, Seoul 131, Korea
Abstract
The structures of dihydropyrimidines synthesized from mono- or dialkyl-guanidine with methyl acrylate were assigned as 1-alkyl-2-amino-(6b) or 1-alryl-2-alkylamino-5,6-dihydropyrirmidin-4-one(6d) by comparing 1H nmr, ir, and uv spectral data with those from 6b and 6d synthesized by the other route. The λmax values of the dihydropyrimidines showed significant differences from those of the hydrochlorides whose significant blue shifts are thought to be a good evidence and a tool for the conjugative system of the two double bonds in 2-aminodihydropyrimidines.
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■ Novel Ring Opening Reaction of 2-Aryl-1,2-benzisoselenazol-3(2H)-one with Thiols
Nobumasa Kamigata,* Mayumi Takata, Haruo Matsuyama, and Michio Kobayashi
*Department of Chemistry, Faculty of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan
Abstract
Reaction of 2-aryl-1,2-benzisoselenazol-3(2H)-one (1) with alkane- and arenethiols in dichloromethane at room temperature gives ring opening adducts, 2-alkyl- and 2-arylthioselenobenzanilides, respectively, probably via nucleophilic reaction of carbonyl oxygen of compound 1 to thiol hydrogen to give 3-hydroxy-2-aryl-1,2-benzisoselenazolium ion and thiolate anion, and subsequent nucleophilic attack on selenium atom by the resulting thiolate anion to generate the final ring opening product.
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■ Isolation of Photo-Diels-Alder Mono-adducts of 4,6-Dimethyl-2-pyrone and Formation of Cross-adducts
Tetsuro Shimo, Hiroyuki Yoshimura, Hisako Uemura, Kenichi Somekawa,* and Otohiko Tsuge
*Department of Applied Chemistry, Faculty of Engineering, Kagoshima University, Korimoto, Kagoshima 890, Japan
Abstract
The Diels-Alder mono-adducts between 4,6-dimethyl-2-pyrone and olefinic dienophiles could be isolated from the low temperature photochemical reactions. The adducts reacted with second olefins to afford cross-adducts with the concurrent decarboxylation. Irradiation of the cross-adducts to p-benzoquinone gave cage compounds.
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■ One Carbon Unit Transfer to Enamines through Oxazolidines and Tetrahydro-2H-1,3-oxazine
Harjit Singh,* Rakesh Sarin, and Kamaljit Singh
*Department of Chemistry, Guru Nanak Dev University, Amritsar -143 005, Punjab, India
Abstract
Oxazolidines and tetrahydro-2H-1,3-oxazine undergo acid catalysed transfer of C2 carbon unit inbetween two nucleophilic carbons of stabilised enamines.
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■ A Convenient Method for the Synthesis of Diiodo Compounds. Facile Cleavage of Cyclic Ethers by Phenyl Dichlorophosphate and Sodium Indide
Hsing-Jang Liu,* Lisa M. Shewchuk, and Montse Llinas-Brunet
*Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
Abstract
Cyclic ethers were found to react readily with phenyl dichlorophosphate and sodium iodide to give diiodo compounds under mild reaction conditions.
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■ Organogerminium Compounds: First General Methods for Synthesis of Bioactive Trithiagermatranes with Novel Functional Groups
Norihiro Kakimoto,* Katsuyuki Sato, Masanao Matsui, Toyozo Takada, and Mitsuo Akiba
*Asai Germanium Research Institute, 1-6-4, Izumihon-cho, Komae-shi Tokyo 201, Japan
Abstract
The first general methods for the synthesis of 1-substituted trithiagermatranes (3) have been developed using the reaction of tris-(2-mercaptoethyl)amine with trimethoxygermyl compounds (5), sesquioxides (6) and sesquisulfides(7). These newly prepared compounds were found to have the capacity to relieve pain, thus indicating them to have strong inhibitory activity toward a decomposition enzyme for enkephalin which is an opioid peptide in a living body.
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■ Cyclization of Dinitriles by Hydrogen Halides. 3. The influence of the Tautomerism
Pedro Victory* and Miquel Garriga
*Departmento de Química Orgánica, Instituto Químico de Sarriá, Universitat de Barcelona, 08028 Barcelona, Spain
Abstract
In order to study the possible influence of the tautomerism in the direction of cyclization by hydrogen halides of the 6-cyanamino-5-cyano-3,4-dihydro-2-pyridones (3), the non-tautomeric N-methylcyanamino substituted derivatives 10 have been synthesized. The reaction of 10 with hydrogen halides leads regiospecifically to the 4-halogeno-2-imino-1-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones 12, 13 and 14, showing the insufficient reactivity of the N-cyano group in front of the conjugated one. On the basis of the results of the cyclization of 10, an interpretation of the more complex cyclization of 3 is proposed.
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■ Preparation of 5-Ethoxycarbonyl- and 5-Cyano-5,6-dihydro-3,7-diphenyl-4H-diazepines and Their Halogenations
Kichinosuke Kamata and Otohiko Tsuge*
*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan
Abstract
5-Ethoxycarbonyl- and 5-cyano-5,6-dihydro-3,7-diphenyl-4H-1,2-diazepines were prepared and their halogenations were investigated under various conditions. The halogenation products were found to be strongly dependent upon the nature of 5-substituents as well as the reaction conditions.
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■ A Practical and Short Acess to 4-Hydroxy-3-indolecarbaldehyde and Its Application for the Synthesis of Pindolol Analog
Masanori Somei,* Etsuo Iwasa, and Fumio Yamada
*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
4-Hydroxy-3-indolecarbaldehyde (1) is produced simply by heating (3-formylindol-4-yl)thallium bis-trifluoroacetate with copper sulfate in N,N-dimethylformamide and water. Alkylation of 1 afforded predominantly 1-alkyl derivatives. Utilizing these results pindolol analog, 1-allyl-4-(3-t-butylamino-2-hydroxypropoxy)-3-indolecarbaldehyde was synthesized.
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■ Synthesis of Benzannelated Cycl[3.2.2]azine: Benzo[a]cycl[3.2.2]azine
Yoshinori Tominaga,* Yoshihide Shiroshita, Hiromi Gotou, and Yoshiro Matsuda
*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
Benzo[a]cycl[3.2.2]azine (3) was synthesized from 6-cyanobenzo[a]indolizine (4) and dimethyl acetylenedicarboxylate.
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■ Synthesis of 5H-Dipyrido[1,2-a:3’,2’-e]pyrimidin-5-one and 5-H-Pyrido[3’,2’:5,6]pyrimido[1,2-a]quinazolin-5-ones
Ahmed Kamal,* Maddamsetty Venkateswara Rao, and Pralhard Balvantrao Sattur
*Regional Research Laboratory, Hyderabad 500 007, India
Abstract
α-Amino-N-heteroarenes on cyclocondensation with 2-chloropyridine-3-carboxylic acid chloride afford the title compounds 4 and 7. Although compound 4 is obtained in one-pot while compound 7 is formed via its amide intermediate 6.
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■ Synthesis and Activity of a Tetrahydrofolate Inhibitor of the Enzyme N10-Formyl-H4-folate-Met-tRNAfMet Transformylase
Ka-Kong Chan,* Perry Rosen, Anthony Specian, Jr., Herbert Weissbach, and Carlos Spears
*The Department of Chemistry Research, Hoffman-La Roghe Inc., Nutley, New Jersey 07110, U.S.A.
Abstract
The N-formylmethionine-tRNAfMet is involved in the initiation of protein biosynthesis in procaryotic organisms and is farmed via the transfer of a formyl group from N10-formyltetrahydrofolic acid to the amino group of methionine in Met-tRNAfMet. Based on a proposed intermediate for this formylation step, a transition state analog was designed and synthesized and was shown in vitro to be an excellent inhibitor of the transformylase reaction.
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■ Dihydroisoxazolo[2,3-d][1,4]benzodiazepine Ring System: Stereochemistry and Conformation
Giuseppe Capozzi,* Rosaria Ottanà, Giovanni Romeo, and Nicola Uccella
*Dipartimento di Chimica Organica "Ugo Schiff", Università di Firenze, Via Gino Capponi 9, I-50121 Firenze, Italy
Abstract
The configurational properties of dihydroisoxazolo[2,3-d][1,4]benzodiazepine derivatives, obtained by 1,3-dipolar cycloaddition between chlordiazepoxide and various substituted alkynes, have been determined by 1H nmr spectroscopy, largely by computer-simulation of lanthanide induced shifts (LIS). Cycloadducts exist in solution as a 3:2 mixture of two lnterconvertible diastereoisomers, which are the result of the heptaatomic ring mobility. The stereochemistry of examined derivatives has been found appropriate to determine the further rearrangement to pyrrole-fused quinoxalines, observed in this new tricyclic system.
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■ Carbene versus Dimer Formation from Diazo Derivatives: The Anomalous Behaviour of 2-Diazothiazolines
Josep Castells,* Francisco López Calahorra, and Fernando Geijo
*Departmento de Química Orgánica, Instituto Químico de Sarriá, Universitat de Barcelona, 08028 Barcelona, Spain
Abstract
Different oxidation procedures of 2-thiazolinone hydrazones, the anomalous behaviour of the resulting 2-diazothiazolines and a quantum-theoretical interpretation based in MNDO calculations are reported.
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■ Synthesis and Pharmacological Activity of C(1)- and N(2)-Substituted β-Carboline Derivatives
Ralf Plate, Rutger J. F. Nivard, Harry C. J. Ottenheijm,* Julianna Kardos, amd Miklos Simotyi
*Department of Organic Chemistry, University of Nijmegen, Toernooiveld, 6525 ED Nijmegen, The Netherlands
Abstract
A series of C(1) as well as N(2)-hetero-substituted β-carbolines has heen synthesized from indoles via N-hydroxytryptophan derivatives (Schemes I and II). Preliminary pharmacodynamical data are provided (Tabel I). Of the β-carbolines 4,5,14-16 prepared, the compounds 4,5 and 14 show appreciable in vitro affinity towards the benzodiazepine receptor.
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■ Attempted Intramolecular Polonovski Cyclisation of an Indole-linked Quinuclidine Derivative — A Novel Intramolecular Oxygen Transfer Reaction
Robert F. Chapman, Norman I. J. Phillips, and Robert S. Ward*
*Department of Chemistry, University College of Swansea, Singleton Park, Swansea SA2 8PP, U.K.
Abstract
An attempted modified Polonovski reaction on the indole-linked quinuclidine 8 resulted information of the amide 10 by transfer of an oxygen atom from the quinuclidine N to the indole C-2 position.
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■ Mechanism of H/D Exchange in 5-(p-Nitrobenzyl)barbituric Acid
Misa V. Jovanovic* and Edward R. Biehl
*Department of Chemistry, Southern Methodist University, P.O. Box 750314, Dallas, TX 75275-0314, U.S.A.
Abstract
Title compound 1 and related systems exist in DMSO solution as a tautomeric mixture of enol and keto forms which were easily identified by 13C nmr spectroscopy. Base-catalyzed H/D exchange of 1 occurs at both the C-5 and the methylene group. A mechanism to account for the novel H/D exchange at methylene position is proposed.
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■ Pyrazolo[1’,5’:1,6]pyrimido[4,5-d]pyridazin-7(8H)-one: A New Heterocyclic Ring System from Isoxazolopyridazinones
Vittorio Dal Piaz,* Giovanna Ciciani, and Stefano Chimichi
*Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via Gino Capponi 9, I-50121 Firenze, Italy
Abstract
Treatment of isoxazalo[3,4-d]pyridazin-7(6H)-ones (1a-d) with hydrazine afforded the pyrazole derivatives (3a-d) which were converted in high yields into the new pyrazolo[1’,5’:1,6]pyrimido[4,5-d]pyridazin-7(8H)-ones (4a-d) by ring-closure with acetic anhydride.
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■ Synthesis of 4-(4-Indolyl)-3-oxobutanoic Acid Derivatives from 5-Halo-4-oxo-4,5,6,7-tetrahydroindoles
Masakatsu Matsumoto* and Nobuko Watanabe
*Sagami Central Research Center, 4-4-1 Nishi-Ohnuma, Sagamihara, Kanagawa 229-0012, Japan
Abstract
The reaction of 5-halo-4-oxo-4,5,6,7-tetrahydroindoles with dianion of acetoacetic acid esters or N,N-dimethylamide followed by dehydration and dehydrohalogenation gave 4-(4-indolyl)-3-oxobutanoic acid derivatives. 4-Acetonylindoles with benzoyl and p-toluenesulfonyl at γ-position of the side chain were also synthesized.
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■ A Facile Synthesis of 4-(Cyanomethyl)indoles and 4-(Ethoxycarbonylmethyl)indoles from 5-Halo-4-oxo-4,5,6,7-tetrahydroindoles
Masakatsu Matsumoto,* Nobuko Watanabe, and Yasuko Ishida
*Sagami Central Research Center, 4-4-1 Nishi-Ohnuma, Sagamihara, Kanagawa 229-0012, Japan
Abstract
4-(Cyanomethyl)indoles and 4-(ethoxycarbonylmethyl)indoles were synthesized from 5-halo-4-oxo-4,5,6,7-tetrahydroindoles by means of Horner-Wittig reaction and successive dehydrohalogenation.
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■ Isoazadirolide, a New Tetranortriterpenoid from Azadirachta indica A. Juss (Meliaceae)
Salimuzzaman Siddiqui,* Bina Shaheen Siddiqui, Shaheen Faizi, and Tariq Mahmood
*H. E. J. Postgraduate Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan
Abstract
A new ring-C seco tetranortriterpenoid γ-hydroxybutenolide named as isoazadirolide, has been isolated from the acidic fraction of the fresh, undried, winter leaves of Azadirachta indica A.Juss (neem), along with a coumarin identified as scopoletin. The structures of these compounds have been established through chemical and spectral studies. It is the first instance of isolation of a coumarin from any of the various parts of neem tree.
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■ Carbon-13 NMR Studies on Some Quinoxaline Amino Esters and Their N-Oxides
Salim S. Sabri,* Mustafa M. El-Abadelah, Hasan I. Tashtoush, and Helmut Duddeck
*Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan
Abstract
Carbon-13 chemical shift assignments are reported for a series of N-(2-quinoxaloyl)-α-amino esters, their mono- and di-N-oxides as well as their C-3 methyl analogues. The influences of substituents at C-2 and/or C-3 on the N-oxidation shifts are discussed in terms of mesomeric states and intramolecular hydrogen bridging.
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■ Synthesis of 2H-Pyrazolo[3,4-c]quinoline Derivatives by One Pot Rearrangement of Phenylhydrazones of 3-Acylindoles
Giuseppe Cusmano,* Gabriella Macaluso, Nicolò Vivona, and Michele Ruccia
*Instituto de Chimica Organica, Facolta de Scienze, Università digli Studi di Palermo, 20 via Archirafi, 90123 Palermo, Italy
Abstract
The phenylhydrazones 4a-g of 3-acylindoles led to the 2-phenyl-2H-pyrazolo[3,4-c]quinoline derivatives 9a-e and 10a-b. The reaction mechanism proposed involves an acid catalyzed 6Π heteroelectrocyclic reaction and a ring opening to the pyrazole derivatives 8 followed by a spontaneous ring closure of the latter compounds.
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■ Hofmann Degradation of 2,3-Dihydro-9-phenyl-1H,9H-pyrazolo[1,2-a]indazole Derivatives
Yasuo Fujimura* and Masatomo Hamana
*Central Research Laboratories, Chugai Pharmaceutical Company, Ltd., Takada 3-41-8, Toshima-ku, Tokyo 171, Japan
Abstract
Treatment of 2,3-dihydro-9-phenyl-1H,9H-pyrazolo[1,2-a]indazoles (2)with alkyl iodides followed by heating with potassium hydroxide solution gave 1-alkyl-6-phenyl-1,2,3,4-tetrahydro-1,5-benzodiazocines (A) and 2-(3-alkylaminopropylamino)benzophenones (B) through the 4-alkyl and the 10-alkyl quaternary salts of 2, respectively.
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■ Synthesis of Substituted 4,5-Dihydro-4-oxo-2-[(2-trans-phenylcyclopropyl)amino]-3-furancarboxylic Acids and Ethyl Esters
Vassil St. Georgiev,* Robert A. Mack, and C. Richard Kinsolving
*Department of Organic Chemistry, Pharmaceutical Division, Pennwalt Corporation, Rochester, New York 14623, U.S.A.
Abstract
The synthesis and biological activity of a series of novel 4,5-dihydro-4-oxo-2-[(2-trans-phenylcyclopropyl)amino]-3-furancarboxylic acids and their ethyl esters, is described. When tested in broth and agar dilution tests, some of the title compounds exerted in vitro antimicrobial activity against a number of gram-positive and gram-negative bacteria, as well as in vitro antifungal activity against dermatophyte and yeast fungi.
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■ Synthesis of 4-Substituted 3-Pyridyl Ketones
Daniel L. Comins* and Eric D. Stroud
*Department of Chemistry abd Biochemistry, Utah State University, Logan, Utah 84332-0300, U.S.A.
Abstract
In the presence of a catalytic amount of cuprous iodide, the addition of Grignard reagents to the 1-phenoxycarbonyl salts of 3-acylpyridines gives 3-acyl-4-alkyl-1-phenoxycarbonyl-1,4-dihydropyridines. The crude dihydropyridines were aromatized with hot sulfur to give 4-substituted 3-pyridyl ketones.
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■ Preparation of 6-(3,5-Dimethylisoxazol-4-yl)-6-oxohexanoic Acids via 3,5-Dimethylisoxazol-4-ylmagnesium Iodide or 3,5-Dimethylisoxazol-4-yllithium
Teresa Antequera, Vincente Ramos, and Tomas Torroba*
*Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Extremadura, Avenida de Elvas s/n, 06071-Badajoz, Spain
Abstract
3,5-Dimethylisoxazol-4-ylmagnesium iodide 1 or 3,5-dimethylisoxazol-4-yllithium 3 react with cyclohexanones 2a-c to give 4-(methylcyclohexen-1-yl)-3,5-dimethylisoxazoles 4a-c which in turn gave the title acids by oxidation.
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■ Reinvestigation of a Cyclization Reaction of 2-Hydrazino-3-(1H-pyrrol-1-yl)pyridine
Norton P. Peet* and Shyam Suder
*Indianapolis Center, Merrell Dow Research Institute, 9550 Zionsville Road, Indianapolis, Indiana 46268-0470, U.S.A.
Abstract
The reaction of 2-hydrazino-3-(1H-pyrrol-1-yl)pyridine (3) with acetylacetone affords 2-(3,5-dimethyl-1H-pyrazol-1-yl)-3-(1H-pyrrol-1-yl)pyridine (7) rather than 3,5-dimethyl-10-(1H-pyrrol-1-yl)pyrido[2,1-c][1,2,4]triazepine (5), as previously reported.
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■ Polycyclic N-Hetero Compounds. XXVIII. Synthesis and Antidepressive Evalution of 4-Substituted 9-Chloro-6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepine
Takashi Hirota,* Masami Fukumoto, and Kenji Sasaki
*Okayama UniversityFaculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
4-Substituted 9-chloro-6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepines (IIIa-j) were synthesized by the reaction of 4,9-dichloro-6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepine (I) with amines (IIa-j) and their antidepressive activities were investigated.