HETEROCYCLES

■ A New Alkylation of Pyridazines with Nitromethane and Nitroethane

Mitsuji Yanai,* Shigeko Takeda, and Makoto Nishikawa

*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

3-Hydroxy-4-ethoxycarbonyl-6-chloropyridazine (I) reacts with nitromethane and nitroethane to give the respective 5-methyl (I-A) and 5-ethyl (I-B) derivatives when their solution in DMSO is stirred at room temperatures in the presence of potassium carbonate. The scope of this type of nuclear alkylation of pyridazines is rather wide as shown in Table.

■ The Reaction of 6-Methyl-7-azido-5,8-quinolinediones with Cyclic Secondary Amines. A Convenient Synthesis of 6-Substituted Aminomethyl-7-amino-5,8-quinolinediones

Shigetaka Yoshina* and Hsien-Saw Kuo

*Faculty of Pharmacy, Meijo University, 150 Yagoto, Tempaku-ku, Nagoya, Aichi 468-8503, Japan

Abstract

The 6-methyl-7-azido-5,8-quinolinediones (Ia,b) react with amines (pyrrolidine, piperidine and morphorine) in benzene solution to give 6-substituted aminomethyl-7-amino-5,8- quinolinediones(IIIa-e).

■ Synthesis of the 6-Aza Analog of Trimethoprim

Khizar Wasti and Madeleine M. Joullié*

*Department of Chemistry, University of Pennsylvania, 231 South 34th Street Philadelphia, PA 19104-6323, U.S.A.

Abstract

The synthesis of the 6-aza analog of Trimethoprim, 3,5-diamino-6-(3,4,5-trimethoxybenzyl)-1,2,4-triazine, a potential antibacterial and antimalarial agent, is described.

■ A Novel Displacement Reaction of 1-Ethyl-6,7-methylenedioxyquinolines with Nucleophiles

Hideo Agui and Takenari Nakagome*

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

Abstract

The reaction of 4-amino- (3a) and 4-anilino-3-carboethoxy-1-ethyl-6,7-methylenedioxyquinolinium iodide (3b) with nucleophilic reagents produced 7-substituted 4-amino-3-carboxy-1-ethyl-6-hydroxyquinolinium betaines (5b-d) and 7-substituted 1-ethyl-1,4-dihydro-6-hydroxy-4-phenylimino-3-quinolinecarboxylic acid (6b-d), respectively, which led to 7-substituted 1-ethyl-1,4-dihydro-6-hydroxy-4-oxo-3-quinolinecarboxylic acids (1b-d) by alkaline hydrolysis.

■ Diels-Alder Reaction in a Polar System. Thermal Cycloaddition of 1-Phenyl-2-ethoxycarbonyl-3-benzoyl-Δ²-pyrroline-4,5-dione with Butadienes

Yoshisuke Tsuda,* Yoshie Horiguchi, and Takehiro Sano

*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan

Abstract

In thermal reactions of 1-phenyl-2-ethoxycarbonyl-3-benzoyl-Δ²-pyrroline-4,5-dione (1) with butadienes, two types of [4+2] cycloaddition were observed. One was a formation of pyrano-pyrrole derivative (type A), where butadiene behaved as a dienophile and pyrroline-4,5-dione as a diene. The other was an usual Diels-Alder product (type B). The type A adduct thermally rearranged in a [3,3lsigmatropic manner into the type B adduct. 1-Acetoxy-, 1-sulphenyl-, and 1-trimethylsilyloxy butadienes also cycloadded to 1 and afforded only type B adducts, which were suggested to be formed from the initially generated type A adducts. The similar phenomenon was observed in the cycloaddition reaction of 1 with norbornadiene.

■ Cycloaddition of 2-Phenyl-3-ethoxycarbonyl-Δ²-pyrroline-4,5-dione with Butadiene. Evidence of [1,3]Sigmatropy for Formation of the Diels-Alder Product

Takehiro Sano and Yoshisuke Tsuda*

*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan

Abstract

Thermal and photochemical cycloaddition of 2-phenyl-3-ethoxycarbonyl-Δ²-pyrroline-4,5-dione (1) with butadiene afforded the same 1,2-adduct (2) in reglo- and stereoselective manner. At elevated temperature the 1,2-adduct (2) changed by an 1,3-sigmatropic shift into the normal Dlels-Alder adduct (3). The easiness of sigmatropy was greatly influenced by the nature of N-substituents and decreased by the following order : H > Me > Ph. In case of N-phenyl derivative, the rearrangement was not observed.

■ Crystal Structure of the Photocycloadduct of 1-(4’-Bromophenyl)-2-phenyl-3-ethoxycarbonyl-Δ²-pyrroline-4,5-dione with Butadiene

Takehiro Sano, Yoshisuke Tsuda,* Haruo Ogura,* Kimio Furuhata, and Yoichi Iidaka

*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan

Abstract

The structure of the cycloadduct of 1-[4’-bromophenyl]-2-phenyl-3-ethoxycarbonyl-Δ²-pyrroline-4,5-dione with butadiene was determined by X-ray analysis using a heavy atom method.

■ Photocyclization of N-Chloroacetyl-2-methoxy- and 2,4-dimethoxyphenethylamines to 4-Azabicyclo[5.3.1]undeca-9-ene-3,8-diones

Yohmei Okuno and Osamu Yonemitsu*

*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

When N-chloroacetyl-2,4-dimethoxyphenethylamine (3) was irradiated, photocyclization occurred to form a transient cation intermediate (1), which was immediately attacked by a hydroxide ion to yield 11-hydroxy-10-methoxy-4-azabicyclo[5.3.1]undeca-9-ene-3,8-dione (5). Similarly, on irradiation, N-chloroacetyl-2-methoxyphenethylamine (8) gave the same type compound, 11-hydroxy-4-azabicyclo[5.3.1]undeca-9-ene-3,8-dione (9). Mechanistic consideration was also presented.

■ Studies on the Synthesis of Bisindole Alkaloids. VI. Novel Lactam Derivatives in the Vinblastine Series

James P. Kutney,* John Balsevich, and Gordon H. Bokelman

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

Abstract

The utilization of osmium tetroxide as an oxidant can provide a synthetic entry into lactam derivatives in the bisindole area. In complimentary investigations it was shown that iodine and air oxidation of a series of bisindole alkaloids can also provide some novel lactam derivatives. These substances are important for the purpose of biological evaluation as potential anti-tumor agents and, in particular, for information relating to structure-activity relationships in the clinically important vinblastine family of alkaloids.

■ The Reaction of β-Aminoenones with N-Substituted Ureas

Choji Kashima,* Yasuhiro Yamamoto, Yoshimori Omote, Tatsuo Ohtsuka, and Yoshihiko Tsuda

*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan

Abstract

The reaction of 2-amino-2-hepten-4-one with N-substituted ureas was described as well as 2,4-heptanedione. When the product ratios from both compounds were compared, β-aminoenones were concluded to react selectively. Also the selectivity was depend on the basicity of nitrogen of ureas.

■ The Photochemistry of Aromatic N-Oxides. A Crystal Review

François Bellamy and Jacques Streith*

*Ecole Nationale Supérieure de Chimie de Mulhouse, Université du Haut-Rhin, 68093 Mulhouse, France