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. 16, No. 9, 1981
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■ Reactions of 2-Chloroindoles: Synthesis of 2,2’-Biindolyls
Akinori Kubo* and Keijiro Uchino
*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Abstract
3-Alkyl-2-chloroindoles (2) react with 3-alkylindoles (4) in the presence of boron trifluoride etherate to afford 3,3’-dialkyl-2,2’-biindolyls (3) in good yields.
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■ The Nonregiospecific Condensation of Citral and 2-Hydroxycarbazole
Vinayak V. Kane,* Arnold R. Martin, and Jo Ann Peters
*Department of Pharmaceutical Sciences, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, U.S.A.
Abstract
Condensation of citral and 2-hydroxycarbazole in the presence of pyridine has been shown to be regioselective and not regiospecific as has been reported previously. The isolation, characterization and spectral properties of the major (non linear) and the minor (linear) isomers are described.
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■ Reaction of Phenacyldimethylsulfonium Iodine with o-Phenylenediamines
Shinzo Kano* and Yoko Yuasa
*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
The reaction of o-phenylenediamine with phenacyldimethylsulfonium iodide gave 2-phenylquinoxaline. The same reaction by use of 3,4-diaminotoluene and 1,2-diamino-4-chlorobenzene instead of o-phenylenediamine afforded a mixture of the corresponding 6- and 7-substituted 2-phenylquinoxalines. In the case of 1,2-diamino-4-nitrobenzene, 6-nitro-2-phenylquinoxaline was obtained. On the other hand, the reaction of 1,2-diamino-4-methoxybenzene and phenacyldimethylsulfonium iodide gave 7-methoxy-2-phenylquinoxaline. Furthermore, condensation of maleonitrile with phenacyldimethylsulfonium iodide gave 2,3-dicyano-6-phenylpyrazine.
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■ The Chemistry of 1,6-Diazaphenalene. Electrophilic Substitution and Reaction with Singlet Oxygen
Kamlakar Avasthi, Shieu-Jeing Lee, James M. Cook,* James E. Pickett, and Harry H. Wasserman
*Department of Chemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, U.S.A.
Abstract
The nitration, bromination, acylation, and alkylation of 1,6-diazaphenalene (1) have been investigated as well as the reaction of the title compound with singlet oxygen. These transformations have been compared to similar reactions known to take place with imidazoles.
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■ 2-Azabicyclo[3.2.0]heptane-3,4-diones (6). A Novel Method of Regio-controlled Synthesis of Functionalized Hydroindoles and Erythrinan Derivatives
Takehiro Sano,* Jun Toda, Yoshie Horiguchi, Kazue Imafuku, and Yoshisuke Tsuda
*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
Abstract
A regio-controlled synthesis of functionalized hydroindoles from a Δ2-pyrrolinedione and its application to the synthesis of erythrinan skeleton were described. The method is to construct with [2+2] photocycloaddition of a trimethylsilyloxybutadiene to a Δ2-pyrrolinedione followed by thermal [1,3]-rearrangement to yield a hydroindole silyl enol ether, which is isomeric with the hydroindole silyl enol ether obtained by Diels-Alder cyclization between the same substrates.
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■ Studies in the Dihydropyridine Series. V. Synthesis of Pyridocarbazole Alkaloids: Olivacine and Guatambuine
James P. Kutney,* Masaki Noda, Morman G. Lewis, Beatrice Monteiro, Danuta Mostowicz, and Brian R. Worth
*Department of Chemisry, University of British Columbia, Vancouver 8, V5T 1W5, Canada
Abstract
The tricarbonylchromium(0) complex 8 effectively stabilized the very reactive dihydropyridine system during one carbon insertion. Release of the complex allowed cyclization to the pyridocarbazole product 13 which was elaborated to olivacine 1 and guatambuine 2.
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■ SRN1 Reaction. Synthetic Application to 4-Azaindoles
Rafael Fontan, Carmen Galvez,* and Pere Viladoms
*Departamento de Química Orgánica, Facultad de Química de Tarragona, Universidad de Barcelona, Pl. Imperial Tarraco s/n, Tarragona, Spain
Abstract
A new synthetic method for 4-azaindoles, based on nucleophilic heteroaromatic substitution via a radical intermediate (SRN1 reaction) is described.
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■ New Iridoid Glucosides, Canpenoside and 5-Hydroxycampenoside, from Campsis chinensis Voss
Shigeru Kobayashi,* Yasuhiro Imakura, Yoshinobu Yamahara, and Tetsuro Shingu
*Faculty of Pharmaceutical Sciences, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Abstract
Two novel iridoid glucosides, campenoside and 5-hydroxycampenoside were isolated from the leaves of Campsis chinensis Voss and their structures were shown to be 2 and 3, respectively.
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■ A Simple Synthesis of the Blue-green Alga Alkaloids, Hyellazole
Seiichi Takano,* Yujiro Suzuki, and Kunio Ogasawara
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
A simple total synthesis of hyellazole (10) isolated from the Hawaiian blue-green alga Hyella caespitosa has been achieved.
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■ An Alternative Synthesis of (±)-Dihydrosetocleavine
Mitsutaka Natusme* and Hideaki Kuratake
*Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158, Japan
Abstract
Synthetic route was developed for 8-oxoergoline derivatives 1d and 1e starting from 4f and 4g by way of 9a and 9b. (±)-Dihydrosetoclavine (3a) was synthesized from 1d.
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■ New Synthetic Applications of 4-Acetoxyazetidin-2-one: Carboxylate and Nitrogen Nucleophile Displacements
Malcolm M. Campbell* and V. John Jasys
*School of Chemistry, University of Bath, Bath, Avon. BA2 7AY, U.K.
Abstract
Reaction conditions for displacement of the acetate group in 4-acetoxyazetidin-2- one by carboxylate and nitrogen nucleophiles have been studied, giving firstly, a 4-malonyloxyazetidin-2-one from which was synthesized the clavulanic acid degradation product benzyl 3,7-dioxo-4-oxa-1-aza[3.2.0.]bicycloheptan-7-one 2-carboxylate, and secondly, new routes to 4-aza substituted azetidin-2-ones.
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■ New Synthesis of Diazepinone Skeleton Using Palladium Catalyzed Carbonylation
Miwako Mori, Minoru Ishikura, Toshihito Ikeda, and Yoshio Ban*
*Faculty of Pharmaceutical Sciences, Hokkaido University, Hokkaido University
Abstract
Palladium catalyzed carbonylation to the secondary amine (10) which was easily prepared from N-methyl-2-bromo-4-chloroaniline (1a) and carbobenzyloxyglycine (2a) gave 3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione derivative (11) in the yield of 30%. N-Acetyl derivative (14) of 8 was treated in the same manner to give the cyclic imide (15) in a fairly good yield and its result constitutes a new synthesis of diazepam (16).
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■ Synthesis of Azapenem and Azacephem Ring System
Isao Nagakura*
*Institute de Chimie Organique, Université de Lausanne, 2, rue de la Barre, CH 1005 Lausanne, Switzerland
Abstract
Novel β-lactam ring systems, 7-oxo-1,3-diazabicyclo[3.2.0]hept-3-ene (III), 7-oxo-1,4-diazabicyclo[3.2.0]hept-3-ene (IV), and 8-oxo-1,3-diazabicyclo[4.2.0]oct-3-ene (V) have been synthesized via cyclization of olefinic azide.
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■ Synthesis of Vinyl-substituted Indolizine Derivatives by a Novel Reaction of Indolizines with Ethoxyethylenes Having Electron Withdrawing Substituents
Yoshiro Yamashita, Daisuke Suzuki, and Mitsuo Masumura*
*Department of Applied Chemistry, Faculty of Engineering, University of Tokushima, Minamijosanjima-cho, Tokushima 770-8506, Japan
Abstract
Reactions of indolizine derivatives with electron deficient ethoxyethylenes such as ethoxymethylenemalononitrile gave vinyl-substituted indolizines 3 by the Michael type addition reaction followed by ethanol elimination. Hydrolisis of 3-dicyanovinylindolizines afforded 3-formylindolizines.
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■ The Intramolecular Cycloaddition Reaction of o-Cinnamyloxybenzylidene(methoxycarbonyl)phenylmethylamines
Otohiko Tsuge,* Kazunori Ueno, and Ikuhiko Ueda
*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan
Abstract
o-Cinnamyloxybenzylidene(methoxycarbonyl)phenylmethylamines undergo an intramolecular cycloaddition via their 1,3-dipolar tautomers to the alkenyl group, affording three stereoisomeric cycloadducts.
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■ Synthesis of Methyl 3(R)-Methyl-5-oxopentanoate, a Potential Chiral Synthon for Versatile Natural Products, from Common Chiral Intermediates
Seiichi Takano,* Ken’ichi Masuda, and Kunio Ogasawara
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Conversion of both 3(R)-methylcyclopentanone (4) and ι-menthone (8) into methyl 3(R)-methyl-5-oxopentanoate (7) and its derivatives through a α-diketone monothioketal intermediate has been achieved. Using these chiral products as common synthons, an enantioselective route to rose oxide[(4R)-(21)] and its enantiomer[(4S)- (21)] has been developed.
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■ Synthetic Studies on the Lycopodium Alkaloids. A Formal Total Synthesis of (±)-Lycodoline
Sang-Won Kim,* Ikuo Fujii, Keishiro Nagao, and Yutaka Ozaki
*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
Abstract
The tricyclic amine (10) was reacted with the acid chloride (17) to afford the amide (18), which was converted in 3 steps into the amino-alcohol (16). Its preparation constitutes a formal total synthesis of (±)-lycodoline.
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■ New Condensed Triheterocyclic Systems Pyrrolothienopyrimidines
Yamien Effi, Michel Cugnon de Sevricourt, Sylvain Rault, and Max Robba*
*Laboratoire de Chimie Thérapeutique, U. F. R. des Sciences Pharmaceutiques, Université de Caen, 1, rue Vaubénard, 14032 Caen Cedex, France
Abstract
Cyclisation of the azide derivative of the 1-(3-thienyl) pyrrolylcarboxylic acid resulted in the formation of 4,5-dihydropyrrolo[1,2-a]thieno[2,3-e]pyrimidin-4-one.
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■ A Facile Route to 1-Acetoxy- and 1-Methoxyindols
Masanori Somei* and Toshiya Shoda
*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
A simple and practical synthetic method for 1-acetoxy- and 1-methoxyindoles from 2-nitrotoluene is described.
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■ Synthesis of 9-Substituted 1-Nitro- and 1,7-Disubstituted Phenothiazines via Smiles Rearrangement
Radha Raman Gupta,* Gopal Singh Kalwania, and Mahendra Kumar
*Department of Chemistry, University of Rajasthan, Jaipur 302 004, India
Abstract
Substituted phenothiazines without nitro group at position-1 have been prepared via Smiles rearrangement of 2-formamido-2’-nitro-3,4’-disubstituted diphenyl sulphides. The latter were obtained by the action of formic acid on 2-amino-2’-nitro-3,4’-disubstituted diphenyl sulphides which have been prepared by condensing substituted o-aminothiophenol with o-halonitrobenzenes. 9-Substituted 1-nitrophenothiazines have also been synthesised by Smiles rearrangement in situ which involves condensation of 2-amino-3-chloro/methoxy thiophenols with 2,6-dinitrochlorobenzene in the presence of ethanolic sodium hydroxide. All the synthesised compounds have been characterised by IR, NMR and Mass spectral studies.
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■ Synthesis of Some Heterocyclic Compounds from Phosphorus Ylides
Shubha Verma, Narendra Mohan Kansal, Ram Sujan Mishra, and Mishri Mal Bokadia*
*School of Studies in ChemistryVikram University, Ujjain-456 010, M.P., India
Abstract
A series of phosphorus heterocyclic compounds have been prepared from phosphorus ylides and carbonyl compounds. The ylides have been prepared using carbene method under different experimental conditions giving rise to new types of ylides.
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■ Fluorine Containing Bioactive Heterocycles. Part III: Synthesis of Some New Fluorine Containing Phenylglyoxals and 1,2,4-Triazine Derivatives
Krishna C. Joshi,* Kalpana Dubey, and Anshu Dandia
*Department of Chemistry, University of Rajasthan, Jaipur 302 004, India
Abstract
Some medicinally important new fluorine containing phenylglyoxals have been synthesized by selenium dioxide oxidation of appropriate fluorinated acetophenones and characterized by spectral studies. The phenylglyoxals were treated with thiosemicarbazide to give corresponding thiosemicarbazones (III) which were cyclized, in situ, to yield 5-(fluorophenyl)-1,2,4-triazine-3(2H)-thiones. The 5-(4-fluorophenyl)-1,2,4-triazine-3-(2)-thione (IV) undergoes nucleophilic displacement when refluxed with hydrazine hydrate to give corresponding 3-hydrazino-5-(4-fluorophenyl)-1,2,4-triazine. The hydrazino derivative reacts with fluorinated 1,3-diketones, in glacial acetic acid yielding 5-(4-fluorophenyl)-3-[1-(3,5-disubstituted)pyrazolyl]-1,2,4-triazines (VII). All synthesized compounds have been characterized on the basis of elemental analyses, ir, pmr and 19F nmr studies.
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■ A Convenient Synthesis and Reactions of Spiro[3H-Indole-3,2’-thiazolidine]-2,4’(1H)-diones
Krishna C. Joshi,* R. Pathi, and Pooran Chand
*Department of Chemistry, University of Rajasthan, Jaipur 302 004, India
Abstract
Spiro[3H-indole-3,2’-thiazolidine]-2,4’(1H)-diones have been obtained by the condensation of indole-2,3-dione, aromatic amine and mercaptoacetic acid without isolating the intermediates i.e., isatin-3-anils. The spiro compounds have further been subjected to Mannich reaction, acetylation and chloracetylation. All the synthesized compounds have been characterized on the basis of elemental analyses and ir and pmr.
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■ 1,2,5-Thiadiazole-1-oxides. I. Synthesis and Reactions of Alkoxy and Alkylthio Analogs
Sandor Karady,* Joseph S. Amato, Daniel Dortmund, and Leonard M. Weinstock
*Division of Merec and Co., Inc, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065, U.S.A.
Abstract
Diethoxy and dithiomethyl 1,2,5-thiadiazole oxides were synthesized from the corresponding oxalimidates with thionyl chlorides. The alkoxy and alkythio groups were readily replaced by amines, carbon nucleophiles and hydroxide. The resulting hydroxy compounds were alkylated and acylated on the ring nitrogen. The N-alkyl products could be also obtained by thermal O to N rearrangement of the alkoxy derivatives.
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■ 1,2,5-Thiadiazole-1-oxides. II. The Chemistry of the Amines
Sandor Karady,* Joseph S. Amato, Daniel Dortmund, Robert A. Raemer, and Leonard M. Weinstock
*Division of Merec and Co., Inc, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065, U.S.A.
Abstract
Amino-substituted 1,2,5-thiadiazole-1-oxides form salts with NaOMe or NaH. These reacted with alkyl halides, acyl chlorides, isocyanates and methyl acrylate to afford ring nitrogen substituted products. The 3-amino, 4-ethoxy analog participates in a self condensation with KOH to form bis-thiadiazolopyrazine oxide dipotassium salt. Alkylation of this with benzyl bromide afforded a dibenzyl derivative with the benzyl groups attached to the central pyrazine nitrogens. Alkylaminothiadiazole oxides cyclized with the diethoxy derivatives to produce similar tricyclic compounds. These tricyclic bis sulfoxides formed diastereomers, indicating that the sulfur is pyramidal and the two forms are stable, i.e. there is no sulfur inversion at room temperature.
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■ Activated Lactams. Ring-expanding Reaction of Ketene-S,N-acetals with Dimethyl Acetylenedicarboxylate
HIroki Takahata, Akira Tominaga, and Takao Yamazaki*
*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
Reaction of ketene-S,N-acetals (1a,b,c) with DMAD gave ring-expanded products (3a,b,c) in good yields. In a similar manner, the reaction of ketene-S,N-acetal derivatives (4a,b,c) also afforded the corresponding ring-enlarged compounds (5a,b,c).
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■ α,β-Unsaturated Carboxylic Acid Derivatives. 20. N-Methylation of α-Dehydroamino Acid Ester and Its Cyclic Dipeptide from Various Routes
Chung-gi Shin,* Yoshiaki Sato, Masato Hayakawa, Masamichi Kondo, and Juji Yoshimura
*Departmnet of Applied Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan
Abstract
The selective N-methylation of 1-, 4-, and 1,4-positions of individual 3- and 3,6-dialkylidene-2,5-piperazinediones (PDO) either by the cyclization of α-dehydroamino acid ester with methylamine or by the reaction of PDO with methyl iodide in the presence of sodium hydride was performed to give the desired product in a fairly good yield.
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■ A Simple Potosynthesis of Pyrroloindoloquinones
Mitsuo Akiba,* Satoshi Ikuta, and Toyozo Takada
*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
The improved photoreaction of pyrrolidino-1,4-benzoquinones having the active methylene groups afforded a simple and preparative route to the synthesis of pyrroloindoloquinones, which were the mother framework of mitomycins.
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■ A Short Synthesis of 3-Oxo-1,2,3,4,5,6,7,8-octahydroisoquinoline-1-spiro-1’-cyclohexane
Kai S. Ng, Richard E. S. Sutcliffe, Peter S. Rutledge,* and Paul D. Woodgate
*Department of Chemistry, University of Auckland, Private Bag 92019, Auckland, New Zealand
Abstract
Equimolar amounts of cyclohexanone and 1-cyclohexenylacetonitrile in polyphosphoric acid give 3-oxo-1,2,3,4,5,6,7,8-octahydroisoquinoline-1-spiro-1’-cyclohexane (4).
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■ Acetonation of Carbohydrates under Kinetic Control by Use of 2-Alkoxypropenes
Jacques Gelas and Derek Horton*
*Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, U.S.A.
Abstract
Polyols, as exemplified by the sugars and their derivatives, undergo acetonation by 2-alkoxypropenes to give cyclic acetals under kinetic control. The products generally differ from those of conventional thermodynamic acetonation and constitute chirally substituted 1,3-dioxanes, 1,3-dioxolanes, and larger heterocycles, of wide potential utility in synthesis. Free sugars react without tautomerization, and the hemiacetal hydroxyl group does not generally take part in the reaction. The stoichiometry may be controlled to give either mono- or di-acetals, and strained-ring acetals.