HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Alan R. Katritzky's Special Issues, Vol. 37, No. 3, 1994
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■ Photocyclizations of Arylthiofluoroaromatic Compounds: Synthesis of Benzothiophenes
Ziqi Jiang and Jorge Marquet*
*Department of Chemistry, Universitat Autònoma de Barcelona, Bellaterra. 08193-Barcelona, Spain
Abstract
Intramolecular defluoro-photocyclizations of o-arylthiofluoroaromatic compounds in aqueous solution afforded benzothiophene derivatives. Similar photoreactions in acetonitrile led, when possible, to arene thiolate displacement. A mechanistic rationale is discussed.
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■ A Short Synthesis of a Conformationally Restricted Analog of the Neurotransmitter Serotonin with Reduced Basicity
John E. Macor* and Kevin Ryan
*Department of Medical Chemistry, Central Research Division, Pfizer Inc., Eastern Point Road, Groton, Connecticut 06340, U.S.A.
Abstract
The synthesis of a less basic, conformationally restricted analog of serotonin is described [2-(5-methoxyindol-3-ylmethyl)imidazole (1)]. The crucial carbon-carbon bond formation step in this synthesis involves the attack of a 2-lithioimidazole anion on an indole-3-carboxaldehyde derivative.
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■ Synthesis of Chiral Lactams as Templates for Enzyme Inhibitors: An Unusual Annulation in the Intramolecular Wadsworth-Horner-Emmons Reaction
Ramaswamy Shankar and A. Ian Scott*
*Center for Biological NMR, Department of Chemistry, Texas A & M University, College Station, Texas 77843-3255, U.S.A.
Abstract
Intramolecular carbonylolefination of a dipeptide keto phosphonate furnished unexpected lactams through rearrangement of the phosphonate carbanion.
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■ A Study of the Hetero Diels-Alder Reaction of N-Alkyl-2-cyano-1-azadienes with 2-Vinylindole
Bouchra Dufour, Irina Motorina, Frank W. Fowler,* and David S. Grierson*
*Institut des Chimie des Substances Naturelles, C.N.R.S., Avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France
Abstract
The N-alkyl-2-cyano-1-azadienes (2a) and (2b) derived from ethanolamine react with 2-vinylindole under thermal conditions to give the Michael addition adducts (9) and (9’) as the principle product. In the reaction of 2a with vinylindole the Diels-Alder product (11) was also isolated. In the reaction with 2b, formation of compounds (9) was accompanied by the cyclized product (10) and the Diels-Alder adduct (13).
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■ The Trifluoroacetylpyridine Analog of Nicotinamide Adenine Dinucleotide
Peter J. Channon, William J. D. Whish, Roger Harrison, and Robert Eisenthal*
*Biochemistry Department, University of Bath, Bath, BA2 7AY, U.K.
Abstract
3-Trifluoroacetylpyridine adenine dinucleotide has been synthesized enzymically in two steps. The first step involved forming a glycosidic link via the ring nitrogen of 3-trifluoroacetylpyridine to ribose-5-phosphate by reaction of 3-trifluoroacetylpyridine with 5-phosphoribosyl pyrophosphate, catalyzed by nicotinamide phosphoribosyl transferase. The resulting mononucleotide was allowed to react with adenosine triphosphate in the presence of NAD pyrophosphorylase to yield the NAD analog, trifluoroacetylpyridine adenine dinucleotide. The analog behaved as an inhibitor of several NAD-dependent dehydrogenases, but it did not act as a substrate.
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■ Photolytic Generation of N-Acylnitrenium Ions under Neutral Conditions: Synthesis of Polycyclic Lactams
Rudolph A. Abramovitch* and Qing Shi
*Department of Chemistry, Clemson University, Clemson, SC 29631, U. S. A.
Abstract
Intramolecular electrophilic aromatic acylamination has been achieved by the photolysis of N-aroylaminopyridinium tetrafluoroborates under neutral conditions. Acylnitrenium ions were most likely generated which substituted the adjacent ring without undergoing Curtius-type rearrangement.
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■ Reductive Lithiation of Halopyridines Using Lithium Naphthalenide
Yoshinori Kondo, Naoko Murata, and Takao Sakamoto*
*Pharnaceutical Institute, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan
Abstract
Chloropyridines were converted into lithiopyridines via reductive lithiation using lithium naphthalenide as an electron transfer reagent.
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■ Asymmetric Synthesis with Chiral Hydrogenolysable Amines: A New Route to Enantiopure Ethanolamines
Olivier Lingibé, Bernadette Graffe, Marie-Claude Sacquet, and Gérard Lhommet*
*Université P. et M. Curie, Laboratoire de Chimie des Hétérocycles, associé au CNRS, 4 Place Jussieu, case courrier 43, 4 Place Jussieu, F-75252 Paris Cedex 05, France
Abstract
Enantiopure ethanolamines have been obtained via diastereoselective reduction of chiral 2,3-dihydro-6H-1,4-oxazin-2-ones
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■ A Computational Examination of the Anomeric Effect in 1,3-Diazanes
John T. Blair and John Stevens
*Technical Computations, 201-2S-05, 3M center, At. Paul, MN., U.S.A.
Abstract
The anomeric effect was examined for several 1,3-diazane molecules, with computations carried out at the HF/ 6-31G, HF/6-31G*, MP2-FC/6-31G*, and HF/6-311G** levels. Results were analyzed using the NBO method, and concepts of steric hindrance. The effect of n→σ* donation to C-N antibonds appears to control the conformation of diazane systems in which nitrogens are monosubstituted. The computed and experimental results show that specific n→σ* donation to C-N antibonds is irrelevant to the conformations of 1,3-diazane systems in which the nitrogens are trisubstituted. Lone pair electron repulsion would normally operate in the same sense as n→σ* donation. but extensive delocalization of the lone pairs in the σ orbitals appears to diminish this effect to insignificant levels. In the methyl substituted molecules, a generalized and subtle type of steric hindrance seems to be dominant over n→σ* electron donation in determining conformational preference.
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■ A Regiospecific Synthesis of Diphenyl-4-pyridylcarbinol
Gerald L. Goe,* Gregory F. Hillstrom, Ramiah Murugan,* Eric F. V. Scriven, and Angela R. Sherman
*Reilly Industrial inc., Indianapolis, IN 46242-0912, U.S.A.
Abstract
A regiospecific synthesis of diphenyl-4-pyridylcarbinol based on the reaction of benzophenone with 4-cyanopyridine in the presence of sodium [or calcium, lithium and samarium (II)] is reported.
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■ Effect of Substituteents on the 1H and 13C NMR Chemical Shift of trans-Pyridineacrylic and Substituted trans-Cinnamic Acids
Bratislav Jovanovic,* Milica Misic-Vukovic, Sasa Drmanic, and János Csanádi
*Facluty of Technology and Metallurgy, University of Belgrade, 11000 Belgrade, Yugoslavia
Abstract
The principles of linear free energy relationships were applied to the 1H nmr and 13C nmr chemical shifts induced by suhstituents in three isomeric trans-pyridineacrylic and substituted trans-cinnamic acids. The data for the carboxy proton chemical shift correlated well with the simple Hammett equation. Taft’s dual substituent parameter equation was used for the interpretation of the balance of the inductive and resonance effects through the ethylenic bond for the Cα and Cβ 13C nmr shift. Using the nuclear Overhauser method, the conformation of the carboxylic group in 2-pyridineacrylic acid was determined, and its unexpected behaviour in both 1H nmr chemical shifts and in the previously studied reaction with diazodiphenylmethane was interpreted by the increased electron density in the Π-electronic system favoured by the orbital symmetry of the part of the acid molecule.
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■ Transmission of Electronic Effects through the Vinyl Group. Reactivities of the (E)-α-4-Substituted Phenyl-β-pyridineacrylic Acids
Milica Misic-Vukovic,* Sasa Drmanic, and Bratislav Jovanovic
*Facluty of Technology and Metallurgy, University of Belgrade, 11000 Belgrade, Yugoslavia
Abstract
The reactivities of a series of 18 (E)-α-4-substituted phenyl-β-(3N and 4N)pyridineaclylic acids, with a wide range of substituent effects, were investigated in their reaction with diazodiphenylmethane, in dimethylformamide at 30°C, by the known spectrophotometric method. The Hammett equation in its original form has been applied to the results, using the sum of substituent constants from the both aromatic nuclei, but the overall correlation was only fair. Better insight into the transmission of substituent effects was obtained using Taft’s Dual Substituent Parameter (DSP) method, where it was possible to distinguish the contributions from the inductive and resonance effects of the substituents.
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■ Ring Transformation Reactions in 4-Nitroimidazoles Following an Attack of Nucleophiles
Jerzy Suwinski,* Wojciech Pawlus, Ewa Salwinska, and Krzysztof Swierczek
*Instiute of Organic Chemistry and Technology, Silesian University of Technology, ul. Krzywoustego 4, 44-101 Gliwice, Poland
Abstract
It was proved that 4-nitroimidazoles substituted at the nitrogen atom 1 with electron acceptor groups (aryl, arenesulfonyl, nitro) in reactions with some nucleophiles yield the products of ordinary or degenerated imidazole ring transformation (oxadiazoles, triazoles, imidazoles).
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■ A Facile Synthesis of Mercaptopyrazolidine Useful for Construction of the Pendant Moiety of 1β-Methylcarbapenem L-627
Toshio Kumagai, Satoshi Tamai, Takao Abe, Yunosuke Nagase, Yoshinori Inoue, and Yoshimitsu Nagao*
*Faculty of Pharmaceutical Sciences, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Abstract
A 4-mercaptopyrazolidine derivative (3), which is a synthetic intermediate of the pendant moiety of 1β-methylcarbapenem L-627 (2), was synthesized by a practical method starting from hydrazine hydrate.
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■ Substituent Effects in the Reactions of Some 2-Methoxy-3-nitro-5-X-thiophenes with Pyrrolidine and Piperidine in Methanol
Caterina Arnone, Giovanni Consiglio,* Vincenzo Frenna, Elisabetta Mezzina, and Domenico Spinelli
*Dipartimento di Chimica Organica 'A. Mangini', Via S. Donato 15, 40127 Bologna, Italy
Abstract
The kinetics of the title reactions have been studied as a function of amine and methoxide ion concentrations in buffered solutions. All the reactions studied are general base-catalysed. An examination of the catalytic coefficients obtained for each mine-substrate system has showed that the catalysis observed occurs through a SB-GA mechanism and that the general base-catalysed productforming step is controlled by the ring size of the cyclic mine. The Hammett p1 values calculated are consistent with previous evidence concerning the interactions between the substituent at the C-5 para-like carbon atom and the leaving group. Moreover, the results confirm that a methyl group in such a position can behave as a weakly electron-attracting substituent.
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■ Oxidation of N-Acyl Hydrazones of o-Aminoaryl Ketones: Synthesis of 2-Acylaminoindazoles
Antigoni Kotali* and Philip A. Harris
*Laboratory of Organic Chemistry, College of Engineering, University of Thessaloniki, Thessaloniki 54006, Greece
Abstract
Synthesis of 3-shstituted-2-acylminoindazoles via the lead tetraacetate oxidative cyclization of N-carbonylhydrazones of o-aminoarylketones is reported. A mechanism involving formation of organolead, azoacetate and o-quinonemethide imine intermediates isproposed. The formation of the indazole heterocycle was confirmed by an independent synthesis of 2-benzoylamino-3-phenylindazole.
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■ Polycondensed Nitrogen Heterocycles. Part 26. Aminopyrrolo[1,2-f]phenanthridines by Decomposition and Cyclization of 2-Aryl-1-(3-azidophenyl)pyrroles
Anna Maria Almerico, Girolamo Cirrincione, Patrizia Diana, Stefania Grimaudo, Gaetano Dattolo, Enrico Aiello,* Francesco Mingoia, and Paola Barraja
*Instituto Farmacochimico, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy
Abstract
Acid catalyzed decomposition of 1-(3-azidophenyl)pyrroles (8a-d) afforded the 6-amino- and 8-aminopyrrolo[1,2-f]phenanthridines of type (11) and (12) through cyclization of the intermediate protosolvated arylnitrenium ions (9). In the case of azide (8a,b) intermolecular side-reactions led also to the hydroxyphenyl derivatives (10).
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■ Selective N-Alkylation of (E)-Urocanic Acid
Nancy Lauth-de Vinguerie, Natalia Sergueeva, Monique Damiot, Hiba Mawlawi, Monique Riviere, and Armand Lattes*
*CNRS, Laboratoire IMRCP, Université Paul Sabatier, 118, route de Narbonne, 31062 Toulouse Cedex 04, France
Abstract
Various methods of selective alkylation of the N (t)- and N (Π)- nitrogen atoms of (E)- urocanic acid derivatives are reported. Solid-liquid phase transfer catalysis gave the best results for N (t)-alkylation of urocanic acid alkyl esters. Liquid-liquid phase transfer catalysis allowed direct N (t)-alkylation of urocanic acid itself. The N (Π)-nitrogen atom was alkylated after protection of the N (t)-nitrogen with a phenacyl group.
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■ Use of 3,3'-Polymethylene-bridged Thiazolium Salts Plus Bases as Catalysts of the Benzoin Condensation and Its Mechanistic Implications: Proposal of a New Mechanism in Aprotic Conditions
Francisco López-Calahorra,* Josep Castells, Laura Domingo, Josep Martí, and Josep M. Bofill
*Departamento de Química Orgánica, Universitat de Barcelona, Martí i Franques, 1-11, E-08028 Barcelona, Spain
Abstract
3,3’-Polymethylene-bridged thiazolium and benzothiazolium salts are used as precatalysts for the benzoin condensation and it is found that catalytic activity depends strongly on the methylene bridge length. This result supports our previous postulation that, at least in strictly aprotic medium, bis(thiazolin-2-ylidene)s, and not thiazolin-2-ylidenes, are the catalytic species in the benzoin condensation catalyzed by thiazolium salts plus base. As a consequence, a new mechanism based in experimental data and AM1 calculations is proposed.
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■ Crystal Structure of 2,2,4,4,6,6-Hexaphenyl-1,3,5-trithia-2,4,6-trigermacyclohexane (Ph2GeS)3
Katsumi Tanaka, Hidetaka Yuge, Keiichiro Ogawa, Shigenobu Aoyagi, and Yoshito Takeuchi
*Department of Chemistry, The College of Arts & Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo 153, Japan
Abstract
The X-ray crystallographic analysis of 2,2,4,4,6,6-hexaphenyl-1,3,5-trithia-2,4,6-trigermacyclohexane (2) indicates that the six membered ring (Ph2GeS)3 is a twist boat which contrasts to a nearly flat structure observed for the (Ph2GeO)3 ring.
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■ On the Reduction of vic-Dioxopyrrolo[2,3-b]indoles with Lithium Aluminum Hydride
Gert Kollenz* and Chang He Xi
*Institute of Organic Chemistry, Karl-Franzens-University Graz, Heinrichstr. 28, A-8010 Graz, Austria
Abstract
Dioxopyrrol[2,3-b]indoles and their structural analogues, diaza[n,3,3]propellanediones were reduced by lithium aluminum hydride affording their hydrogenated derivatives (1) and (2), each of them representing a mixture of diastereomers. Under equal reaction conditions an open-chain compound (3) was obtained by reduction of 2,3-dioxo-8,8a-diphenyl-1,2,8,8a-tetrahydropyrrolo[2,3-b]indole. 3 cyclizes with oxalyl chloride affording 4. Under acidic conditions 1 and 2 could be decomposed to the indole derivatives (5) and (6), respectively.
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■ Synthesis and Flash Vacuum Pyrolysis of Isoxazolo- and Isothiazolo[5,4-d]pyrimidines
C. Oliver Kappe, Robert Flammang, and Curt Wentrup*
*Department of Chemistry, The University of Queensland, Brisbane, Qld 4072, Australia
Abstract
The multi-step synthesis of isothiazolo[5,4-d]pyrimidines (1c,d) and isoxazolo[5,4-d]pyrimidine (1b) is described. Flash vacuum pyrolysis of 1b leads to phenyliminopropadienone, Ph-N=C=C=C=O, which was identified by Ar matrix infrared spectroscopy.
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■ Adamantylation of N-Unsubstituted Pyrazole Derivatives: Mechanistic and Structural Studies
Pilar Cabildo, Rosa María Claramunt,* Isabelle Forfar, Concepción Foces-Foces,* Antonio L. Liamas-Saiz, and José Elguero
*Departamento de Química Orgánica y Biologiá, Faclutade de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain
Abstract
Reaction of NH-pyrazoles with 1-bromoadamantane in a high pressure stainless steel autoclave gives regioselectively 1-(1-adamanty1)-or 4-(1-adamantyl)pyrazoles depending on the temperature. A series of cross-experiments allows to establish the mechanism of this reaction. The molecular structure of the most simple derivative, 4-(1-adamantyl) pyrazole (3a), has been determined. Intermolecular N-H···N hydrogen bonds hold the four independent molecules together in a helix system parallel to the c axis. The crystal is built up of two centrosymmetricaliy related helices.
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■ Kinetics of Hydrolysis of 1,3,5-Triazine in Mildly Acidic Media
Marina Privman and Petr Zuman*
*Department of Chemistry, Clarkson University, Postdam, NY 13699-5810, U.S.A.
Abstract
Acid catalyzed hydrolysis of 1,3,5-triazine at pH 2 to 5 is governed by the rate of the ring opening. This follows from the value of the dissociation constant involved (pKa 2.7 at μ = 0.5 and pKa 2.3 at μ = 0.1), from the lack of pH-dependence of concentration of 1,3,5-triazine at t = 0, and from the irreversibility of the studied reaction.
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■ Preparation of 2-Aryl-4a,5-dihydro-4H-[1.3.4]oxadiazino[4,5-a]indole as a [a]-Fused Indoles Derivatives
Kimiyoshi Kaneko,* Kana Watanabe, Masuki Gokita, Koji Torisawa, Asuko Takeda, Akira Kato, and Hajime Katayama
*Niigata College of Pharmacy, 5-13-2 Kamishin'ei-cho, Niigata 950-2081, Japan
Abstract
The formation of 2-aryl-4a,5-dihydro-4H-[1,3,4]oxadiazino[4,5-a]indoles was effected by the intramolecular Mitsunobu reaction between primary hydroxy and NH-amide groups in excellent yield.
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■ Synthetic Studies on Colchicine: Reaction of Homomorphinandienones
Hiromichi Ogasawara, Shin-ichi Tasaki, Fumiaki Mutoh, Hiroshi Hara, Hiroharu Nishikawa, Mitsuaki Tanaka, and Osamu Hoshimo*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12, Ichigaya Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
Abstract
For the purpose of synthetic approaches toward colchicine (2) from O-methylandrocymbine (1a), reaction of homomorphinandienones (1a,b) was carried out. Oxidation of 1a,b with 35% aqueous hydrogen peroxide gave a separable diastereomeric mixture of N-oxides (5,6). Polonovski reaction of the N-oxides (5) with acetic anhydride in CH2Cl2 afforded N-demethyl-N-acetamide (7a), whereas that of 5 and 6 with acetic anhydride in the presence of triethylamine gave enamines (8a,b) together with N-demethyl-N-acetamides (7a,b). Furthermore, reaction of enamines (8a,b) with N-bromosuccinimide in dimethoxyethane-H2O or methanol produced α-bromo amides (9a,b).
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■ The Reaction of Isatin Azomethine Ylides with (Z)- and (E)-2-Oxoindolin-3-ylidene Acetophenones: Concerted vs Apparent Non-conceeted 1,3-Dipolar Cycloaddition
Adele Casaschi, Giovanni Desimoni*, Giuseppe Faita, Anna Gamba Invernizzi, and Paolo Grünanger*
*Dipartamento di Chimica Organica, Università de Pavia, V. le Taramelli 10, 27100 Pavia, Italy
Abstract
The reaction of 1-benzyl-5-bromoisatin with proline, sarcosine, or glycine gives azomethine ylides that can be trapped by (Z)- or (E)-2-oxoindolin-3-ylidene acetophenones acting as dipolmphiles in a 1,3-dipolar cycloaddition. The configuration of the adducts was determined by 1H-nmr with nOe experiments. The kinetically controlled adducts always retain the configuration of the reacting dipolarophile but they can rearrange, sometimes under extremely mild conditions. The rearrangements were demonstrated to involve a 1,3-dipolar cycloreversion/ cycloaddition sequence since the intermediates were trapped by more reactive dipolarophiles.
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■ Synthesis of tert-Butylcyclopentane-fused 1,3-Oxazines and 1,3-Thiazines
Gábor Bernáth,* Zsolt Szakonyi, Ferenc Fülöp, and Pál Sohár
*Institute of Pharmaceutical Chemistry, Albert Szent-Györgyi Medical University, H-6701 Szeged, Eötvös u.6., Hungary
Abstract
From 2-hydroxymethyl-4-ten-butyl-1-cyclopentyes (6) and (S), by different ring-closure methods, a number of tert-butylcyclopentanefused 1J-oxazines and 1,3-thiazines were synthesized.
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■ Substitued Vinyl Azides in Synthesis of Furo[3,2-b:4,5-b']diplyrroles and Pyrrolo[2',3':4,5]furo[3,2-c]pyridines
Alzbeta Krutosiková* and Miloslava Dandárová
*Department of Organic Chemistry, Faculty of Chemical Technology, Slovak Technical University, SK-81237 Bratislava, Slovakia
Abstract
A number of pyrrolo[2’,3’:4,5]furo[3,2-c]pyridines (5a-5d) were prepared by the reaction of corresponding iminophosphoranes (4a, 4b), available from substituted vinylazides (1a, 1b) and triphenylphosphine, with phenyl or 3-chlorophenyl isocyanates. The appropriate vinylazides (1a, 1b) were used for the preparation of substituted furo[3,2-b:4,5-b]dipyrroles (2a, 2b). Compounds (3a, 3b) were prepared in phase transfer catalysis condlions.
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■ Intramolecular Vicarious Nucleophilic Substitution of Hydrogen in 3-Nitrochloroacetanilides. A Synthesis of Oxidole Derivatives
Mieczyslaw Makosza* and Hanna Hoser
*Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O.Box 58, PL-01-224 Warszawa 42, Poland
Abstract
3-Nitrochloroacetanilides were treated with a strong base to form the α-chlorocarbanions, which enter intramolecular reaction with the nitroaromtic rings producing nitrooxindoles.