HETEROCYCLES

■ Neighbouring Group Interaction in ortho-Substituted Aminopyridines. Formation of 1,2,4-Oxadiazolylpyridines and Pyrido[2,3-d]pyrimidines 3-Oxides

Bojan Vercek, Ivan Leban, Branko Stanovnik, and Miha Tisler*

*Department of Chemistry, University of Ljubljana, 61000 Ljubljana, Slovakia

Abstract

Transformations of 2-amino-3-cyanopyridine with hydroxylamine and various one carbon atom connecting reagents are described. Various paths of interconversion of 4-aminopyrido[2,3-d]pyrimidine 3-oxide and 2-amino-3-(1’,2’,4’-oxadiazolyl-3’)pyridine are described. In some of the transformations also a pyrazolo[3,4-b]pyridine derivative was formed.

■ Reactions at C-9 Position of Acridine Derivatives. Part XVIII. On the Mechanism of Hydrolysis (Solvolysis) of 9-Chloroacridine in Aqueous Acetic Acid

Stanislaw Skonieczny*

*Laboratory of Chemistry and Biochemistry of Antitumour Compound, Institute of Organic and Food Chemistry and Technology, Techinical University of Gdansk, 80-952 Gdansk 6, Poland

Abstract

The kinetics of solvolysis of 9-chloroacridine (1) in 80 % aqueous acetic acid and its hydrolysis in aqueous hydrochloric acid of pH from 0 to 3 have been studied. The reaction occurs in two distinct stages in acetic acid but follows pseudo-first-order kinetics with respect to 1 in hydrochloric acid. No traces of the Π-complex (2) suggested for the former case are observed in the u.v. spectra, and reaction rate constant for the hydrolysis in hydrochloric acid are identical with those of the second step of the consecutive reaction in acetic acid at the same concentration of 1. This implies a mechanism with 9-chloroacridine hydrochloride (5) as an intermediate in the solvolysis process. Hydrogen bonded compound 4 is discussed as a possible intermediate in most nucleophilic substitution reactions at 9-position of 1.

■ Oxidation of Reissert Compounds with Molecular Oxygen

Somsak Ruchirawat* and Mayuree Chuankamnerdkarn

*Department of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

Abstract

Oxidation of dihydro Reissert compounds (Ia, b) with molecular oxygen under two-phase catalytic system yielded dihydroisocarbostyril (II). However, 6,7-dimethoxyisoquinaldonitrile (IV) was isolated when Reissert compound (III) was similarly oxidised.

■ Importance of the Baldwin Rules to the Intramolecular Anodic Coupling of Isoquinoline and Indole Derivatives

Malcolm Sainsbury*

*School of Chemistry, University of Bath, Bath, Avon. BA2 7AY, U.K.

Abstract

The coupling reactions of radical cations derived from certain isoquinolines and indoles is favoured only when six membered transition states are involved. In the case of 3-substituted indoles initial attack at position-3 occurs, followed by a selective bond breaking and rearrangement.

■ The Synthesis of Tetrahydrokuwanon C Tetramethyl Ether

Taro Nomura,* Yoshiki Sawaura, Toshio Fukai, Sachiko Yamada, and Shinzo Tamura

*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

The synthesis of tetrahydrokuwanon C tetramethyl ether (XlV) was achieved by Baker-Venkataraman method from 2-hydroxy-3-isopentyl-4,6-dimethoxyisoheptophenone (X) derived from phloroglucinol. From this result, the structures of morusin, cyclomorusin, compound A, oxydihydromorusin (morusinol), and kuwanon C were confirmed as I, II, III, TV, and V, respectively.

■ Oxidative Cyclization of 2-Unsaturated 1,4-Dioximes

Akio Ohsawa, Heihachiro Arai, and Hiroshi Igeta*

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

The major product of the oxidation of 1,4-diphenyl-2-butene-1,4-dioxime (4c) with phenyliodoso bis trifluoroacetate (PITFA) was 3,6-diphenyl-dihydroisoxazoloisoxazole (2c) which had been incorrectly assigned to the 3,6-diphenylpyridazine dioxide (1c) by other authors. Lead tetraacetate was found to be more applicable reagent than PITFA for the preparation of dioxides(1) from 2-unsaturated 1,4-dioximes.

■ The Reaction of O-Ethyl Succinimide with Primary and Secondary Amines. A Simple Synthesis of Some 4(3H)-Quinazolones and Quinazolones Having Propionic Acid at 2-Position

Tatsuo Nagasaka*, Fumiko Hamaguchi, Naganori Ozawa, and Sadao Ohki

*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Abstract

The reaction of O-ethyl succinimide (I) with various primary and secondary amines (II) afforded keto-amidines (III) in satisfactory yields. The treatment of keto-amidines (IIIi, IIIj, and IIIk) prepared from anthranilate and o-acylanilines with sodium in alcohol afforded quantitatively quinazolones (VIa and VIb) and quinazolines (VId and VIe) having propionic acid ester at 2-position. The sequence of these reactions for quinazolones and quinazolines can be carried out in the same reaction-vessel by successive addition of the reagents.

■ Reaction of Conjugated Enamines with Diazonium Salts. A Convenient Synthesis of Cinnoline Derivatives

Chananjah B. Kanner and Upendra K. Pandit*

*Organic Chemistry Laboratory, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands

Abstract

Aryldiazonium salts react with enamine esters and enamine amides to give iminium hydrazones, which cyclize with subsequent deamination to yield cinnoline derivatives.

■ New Synthesis of 2-Aryl-1,2,4-triazine-3,5(2H,4H)-diones (1-Aryl-6-azauracils)

Fumio Yoneda,* Masatsugu Higuchi, and Yoshihiro Nitta

*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan

Abstract

Treatment of 6-amino-5-arylazo-l,3-dimethyluracils with urea gave the respective 6-aryl-1,3-dimethyl-6,7-dihydro- 6-azalumazine-7(6H)-ones, which were hydrolyzed with alkali to afford 2-aryl-1,2,4-triazine-3,5(2H,4H)-dione-6-carboxylic acids (1-aryl-6-azauracil-5-carboxylic acids). Thermal decarboxylation of these carboxylic acids gave the corresponding 2-aryl-1,2,4-triazine-3,5(2H,4H)-diones (1-aryl-6-azauracils).

■ Studies on the Biosynthesis of Bisindole Alkaloids. The Final Stages in Biosynthesis of Vinblastine, Leurosine and Catharine

Kenneth L. Stuart, James P. Kutney,* Toshio Honda, and Brian R. Worth

*Department of Chemisry, University of British Columbia, Vancouver 8, V5T 1W5, Canada

Abstract

Radiolabelling experiments have demonstrated the incorporation by Catharanthus roseus cell free extracts of 3’,4’-dehydrovinblastine into vinblastine, leurosine and catharine. The enzyme catalysed formation of catharine from leurosine indicated that the former is not an artefact.

■ Alknyylation of Halopyridazines and Their N-Oxides Using Pd-Phosphine Complex

Yoshihito Abe, Akio Ohsawa, Heihachiro Arai, and Hiroshi Igeta*

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

3-Alkynylpyridazines and their 1-oxides were synthesized from 3-chloropyridazines and their 1-oxides, respectively, by the modification of the original method for the alkynylation of aryl iodides using [Pd(PPh₃)₂Cl₂-CuI] and Et₂NH (Sonogashira’s method). The N-oxidation of nitrogen atom in the 1-position.

■ Potential Carcinostatic Agents. Pseudo-Glycosidic Derivatives of 5-Fluorouracil

Willebrordus M. Odijk, Martinus J. Wanner, Gerrit-Jan Koomen, and Upendra K. Pandit*

*Organic Chemistry Laboratory, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands

Abstract

The synthesis and carcinostatic properties of pyranyl-, tetrahydrofuryl- and tetrahydrothienyl-derivatives of 5-fluorouracil are described.

■ The Structures of Ovatine, Lindheimerine, and Garryfoline, C₂₀-Diterpenoid Alkaloids of Garrya ovata var. lindheimeri Torr.

S. William Pelletier,* Naresh V. Mody, and David S. Seigler

*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.

Abstract

Chemical investigation of alkaloids from Garrya ovata var. lindheimeri Torr. has led to the isolation and characterization of two new C₂₀-diterpenoid alkaloids, ovatine (1) and lindheimerine (2), as well as the alkaloid garryfoline (3). Ovatine and garryfoline each exists as a mixture of C(20)-epimers; these alkaloids were chemically interconverted in high yield.

■ A New Ring Transformation of Benzorhiazolines to 3-Oxo-2,3-dihydro-4H-1,4-benzothiazines or Benzothiazoles

Mikio Hori,* Tadashi Kataoka, Hiroshi Shimizu, and Yutaka Imai

*Department of Pharmacognosy, Gifu College of Pharmacy, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan

Abstract

A new ring transformation of benzothiazolines to 3-oxo-2,3-dihydro-4H-1,4-benzothiazines or benzothiazoles was found in the reaction of 2,2-dimethyl- (1) or 2-methyl-2-phenylbenzothiazoline (2) with chloroacetyl chloride.

■ Intermediacy of 3’,4’-Dehydrovinblastine in the Biosynthesis of Vinblastine-Type Alkaloids

Kenneth L. Stuart, James P. Kutney,* Toshio Honda, and Brian R. Worth

*Department of Chemisry, University of British Columbia, Vancouver 8, V5T 1W5, Canada

Abstract

Cell free extracts from Catharanthus roseus plants have been used to demonstrate the formation of 3’,4’-dehydrovinblastine and leurosine from radiolabelled catharanthine and vindoline. 3’,4’-Dehydrovinblastine has been established as a precursor to the vinblastine group of alkaloids and a biosynthetic pathway is proposed.

■ Double-Cyclization Reactions of 1-Dibenzylamino-2-propanone and Related Compounds

Hiroaki Takayama,* Takayoshi Suzuki, Masayuki Takamoto, and Toshihiko Okamoto

*Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan

Abstract

1-Dibenzylamino-2-propanone and its 1-methyl derivative, 2-benzylamino-1-cyclohexanone, 2-benzylamino-1-cyclopentanone, and N,N-dibenzyl-p-X(X=H,Br,NO₂)-phenacylamine, by employing 70%-perchloric acid or triflic acid as cyclization catalyst, afforded 1-aza-5-methydibenzo[c,f]bicyclo[3.3.1]nona-3,6-diene and its 9-methyl derivative, 1-azadibenzo[h,m]tricyclo[5.3.3.0^2,7]trideca-8,12-diene, 1-azadibenzo[g,l]tricyclo[4.3.3.0^2,6]dodeca-3,6-diene, and 1-aza-5-p-X(X=H,Br,NO₂)-phenyldibenzo[c,f]bicyclo[3.3.1]nona-3,6 diene, in 74-95% isolated yields, respectively.

■ Synthesis of 1-Methyl-3-γ,γ-dimethylallyl-4,6,8-trimethoxy-2-quinolone, an Alkaloid from Ptelea trifoliata

Pietro Venturella,* Aurora Bellino, and M. Luisa Marino

*Dipartimento di Chimica Organica , Università digli Studi di Palermo, Viale delle Scienze, Parco d‘Orleans II, 90128 Palermo, Italy

Abstract

1-Methyl-3- h; b/-dimethylallyl-4,6,8- trimethoxy-2-quinolone (I), an alkaloid extracted from Ptelea trifolia.a, was synthesized by N,O-dimethylation of 3-k,)(- dimethylallyl-4-hydroxy-6,8-dimethoxy- 2-quinolone (11). 3,3'-Nethyl'enebis-4- hydroxy-6,8-dimethoxy-2-quinolone (111) was also obtained in the reaction of 2,4-dimethoxyaniline with diethyl 2-(3- methyl 2-butenyl) mzlonate.

■ A Simple Synthesis of 9-Aryltheophenyllines and 9-Aryl-8-azatheophyllines

Keitaro Senga,* Yukako Kanamori, and Sadao Nishigaki

*Pharmaceutical Institute, School of Medicine, Keio University, Shinanomachi 35, Shinjuku, Tokyo 160-0016, Japan

Abstract

Treatment of 6-arylamino-1,3-dimethyluracils (I) with diazotized aniline gave 6-arylamino-l,3-dimethyl-5- phenylazouracils (11). Reductive cyclization of (11) with sodium dithionite in formic acid afforded 9-aryl- theophyllines (111). Catalytic reduction of (11) with palladium charcoal and subsequent in situ treatment with sodium nitrite and hydrochloric acid yielded 9- aryl-8-azatheophyllines (IV) .

■ A New Synthesis of 5-Nitrofurylethylene Compounds

Jaroslav Kovác*

*Department of Organic Chemistry, Faculty of Chemical Technology, Slovak University of Technology, SK-812 37 Bratislava, Slovakia

■ Ringschlussreaktionen an Selenocarbonamid-derivativen zu 1,3-Selenazolen, 1,3,4-Aelenadiazinen und 1,3,4-Selenadiazolen

E. Bulka*

*Institut für Chemie und Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Soldtmannstrasse 16, D-17487 Greifswald, Germany

■ Some Applications on the ¹³C NMR in the Field of Heteroaromatic Compounds

José Elguero*

*Laboratoire de Chimie Moléculaire, Université d‘Aix-Marseille III, rue H. Poincaré, 13397 Marseille Cedex 13, France

■ Lactones as Building Blocks for the Synthesis of Alkaloid Like Heterocycles

Felix Zymalkowski* and Werner Meise

*Institute of Pharmacy, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany

■ Synthesis and Structure Determination of Thiazolines and Related Compounds

L. G. Toldy*

*Institute for Drug Research Ltd., H-1325 Budapest POB 82, Hungary

■ Studies on the Synthesis of Clinically Important Anti-tumour Alkaloids of the Vinblastine-vincristine Family

James P. Kutney*

*Department of Chemisry, University of British Columbia, Vancouver 8, V5T 1W5, Canada

■ Relations between the Structure and Reactivity of Bis-quinolizidine Derivatives and Other Cyclic Diamines

M. Wlewiórowski*

*Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O.Box 58, PL-01-224 Warszawa 42, Poland

■ Recent Syntheses of Heteroaronatic Amines by Cyclizations of Nitriles

K. Gewald*

*Institut für Physikalischce Chemie und Elektrochemie, Technische Universität Dresden, Mommsenstr. 13, D-01062 Dresden, Germany

■ Ring Transformations of Heterocycles; A Synthetic Tool

Henk C. van der Plas*

*Laboratory of Organic Chemistry, Agricultural University, De Dreijen 5, 6703 BC Wageningen, The Netherlands

■ Electronic Effects in the Heterocyclic Organosiicon Amines

E. Lukevics*

*Institute of Organic Synthesis, Academy of Science of the Latvian SSR, 21 Aizkraukels, Riga-6, Latvia, Latvia

■ Photochemistry a Modern tool in Heterocyclic Chemistry — Some Selected Examples

Heinrich Wamhoff*

*Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, D-53121 Bonn, Germany

■ The Role of Nitrenes in the Reactions of the Formation of Some Nitrogen Heterocycles

B. V. Ioffe*

*Leningrad University, Russia