HETEROCYCLES

■ Synthesis of Condensed Nitrogen Heterocycles Derived from Indan-1,3-dione

P. V. Padmanabhan, K. J. Jagannadha Rao, D. V. Ramana, and S. R. Ramadas*

*Department of Chemistry, Indian Institute of Technology, Madras, 600 036, India

Abstract

Convenient procedures have been evolved out for the synthesis of condensed nitrogen heterocycles such as indenopyrrole, indenopyridazine, indenodiazepine and a few spiroheterocycles from indan-1,3-dione.

■ Study of the Reactivity of 3-Oxo-1,2,6-thiadiazine 1,1-Dioxides

P. Goya, C. Molina, C. Ochoa, and M. Stud*

*Instituto de Química Médica, C. S. I. C., Calle Juan de la Cierva 3, E-28006 Madrid, Spain

Abstract

Alkylation and glycosidation reactions of 5-amino-3-oxo-2H, 4H-1,2,6-thiadiazine 1,1-dioxide¹ and 3,5-dioxo-2H, 4H, 6H-1,2,6-thiadiazine 1,1-dioxide¹, which is only isolable as salt form² are reported. The structures of the newly synthesized compounds are discussed on the basis of their spectroscopic data.

■ Methylation of Pyridazines. The Crystal and Molecular Structure of 4,5-Diamino-1-methyl-3-methylthiopyridazinium Iodide

Bradford J. Graves, Derek J. Hodgson,* Sinh-Fong Chen, and Raymond P. Panzica

*Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, Chapel Hill, NC 27599-3290

Abstract

The crystal and molecular structure of 4,5-diamino-1-methyl-3-methylthiopyridazinium iodide (3) has been determined. This X-ray crystallographic study corroborates the suggested course of methylation of substituted pyridazines and established the direction of ring closure of mucochloric acid with methylhydrazine.

■ Phenols from Pyrylium Salts

Michael E. Garst* and Janice D. Frazier

*Department of Chemistry (D-006), University of California, San Diego, La Jolla, CA 92093-0682a, U.S.A.

Abstract

Treatment of pyrylium salts 1 and 2 with dimethylsulfonium methylide yields pnenols which appear to arise from an arene oxide.

■ Introducing Amino Group on 1(2H)-Phthalazinone Derivatives

Masayuki Ishikawa,* Yukuo Eguchi, and Akiko Sugimoto

*Tokyo Medical and Dental University, 2-3-10, Surugadai, Kanda, Chiyoda-ku 101-0062, Japan

Abstract

Nitration of 4-ethoxycarbonyl-1(2H)-phthalazinone (4) with KNO₃ and conc sulfuric acid at room temperature afforded the corresponding 5-nitro derivative (5) in about 50% yield. The latter compound was converted to 5-acetylamino-4-hydroxymethyl-1(2H)-phthalazinone (9). The preparation of 4-amino-7-ethoxycarbonyl-6,8-dimethyl-1(2H)-phthalazinone (13) through the Curtius reaction of the hydrazide (10) was also described.

■ Syntheses of 4-Hydrocymethyl-1(2H)-phthalazinone and Its Analogs

Masayuki Ishikawa* and Yukuo Eguchi

*Tokyo Medical and Dental University, 2-3-10, Surugadai, Kanda, Chiyoda-ku 101-0062, Japan

Abstract

4-Hydroxymethyl-1(2H)-phthalazinone (2) was preferably prepared by reduction of 4-ethoxycarbonyl-1(2H)-phthalazinone with NaBH₄ in EtOH in good yield. The synthetic method was applicable for the preparation of 7-ethoxycarbonyl-4-hydroxymethyl-1(2H)-phthalazinone and its 2-phenyl derivative, where the regioselective reduction of the ester at the position 4 was possible, leaving the ester at the position 7 intact. The Grignard reaction of 4-ethoxycarbonyl-1(2H)-phthalazinone was also described.

■ Syntheses of 2-Hydroxymethyl-4(3H)-quinazolinone and Its Analogs

Masayuki Ishikawa* and Yukuo Eguchi

*Tokyo Medical and Dental University, 2-3-10, Surugadai, Kanda, Chiyoda-ku 101-0062, Japan

Abstract

The syntheses of 6-ethoxycarbonyl-2-hydroxymethyl-5,7-dimethyl-4(3H)-quinazolinone, 7-(or 6-)-ethoxycarbonyl-2,6,8-(or 2,5,7-)-trimethyl-3-phenyl-4(3H)-quinazolinone were described. The 3-phenyl-4(3H)-quinazolinone compounds were further converted to the corresponding 2-hydroxymethyl derivative. The starting compounds, 2-amino-4-ethoxycarbonyl-3,5-dimethylbenzoic acid and 2-amino-5-ethoxycarbonyl-4,6-dimethylbenzoic acid were prepared by the Hofmann reaction of the corresponding phthalimide.

■ 1,3-Dipolar Cycloaddition Reactions of Munchnone and Sydnone Derivatives Obtained from 4,5,6,7-Tetrahydrothieno[3,2-c]pyridine-4 and -6-carboxylic Acids

Jean-Pierre Maffrand*

*Department Recherche et Developpement, Linge Hèmobiologie, Parcor, 195, route d’Espagne 31024 Toulouse Cedex, France

Abstract

The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with mesoionic munchnones and sydnones derived from 4,5,6,7-tetrahydrothieno(3,2-c)pyridine-4 and -6 carboxylic acids afforded respectively new ring-fused pyrroles and pyrazoles.

■ Synthesis of (±)-Elaeokanine E and (±)-12-Epielaeokanine D

Toshio Watanabe,* Yoshihiko Nakashita, Sadamu Katayama, and Masashige Yamauchi

*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

The synthesis of (±)-elaeokanine E (1) and (±)-12-epielaeokanine D (8) has been achieved by the stereoselective Birch reduction of epimeric dihydro-γ-pyrone derivatives (6) and (7).

■ Reactions of 3-Hydrazino-5H-1,2,4-triazino[5,6-b]indoles with Trifluoroacetic Anhydride, Acetylacetone, Hexafluoroacetylacetone and Acetophenone

Krishna C. Joshi* and Pooran Chand

*Department of Chemistry, University of Rajasthan, Jaipur 302 004, India

Abstract

3-Hydrazino-5H-1,2,4-triazino[5,6-b]indole affords a tetracyclic ring system containing compound: 3-trifluoromethyl-10H-1,2,4-triazolo[4’,3’:2,3][1,2,4]triazino[5,6-b]indole with trifluoroacetic anhydride. 3-Hydrazino derivatives, react with acetylacetone, in absolute ethanol giving rise to 3-[1-(3,5-dimethylpyrazolyl)]-5H-1,2,4-triazino[5,6-b]indoles while the reaction with hexafluoroacetylacetone gives ccrresponding hydrazone instead of expected 3-[1-(3,5-bis(trifluoromethyl)pyrazolyl)]-5H-1,2,4-triazino[5,6-b]indole. 3-Hydrazino derivatives also condense with acetophenone but the resulting hydrazone does not produce thiazolidinone with mercaptoacetic acid. All the synthesized compounds have been characterized on the basis of elemental analyses and ir, pmr, ¹⁹F nmr and mass spectral studies.

■ Cyclization of Guanidines with α,β-Unsaturated Ketones: Improved Synthesis of 2-Aminodihydropyrimidine Derivatives Containing Guanidine Moiety

Yong Hae Kim,* Cheol Min Yoon, and Nam Jin Lee

*Department of Chemistry, The Korea Advanced Institute of Science, P. O. Box 150 Chong yang ni, Seoul, Korea

Abstract

3,4-Dihydro-2-amino pyrimidine derivatives 4a, 4b, 4c, 4d, 4e and 4f containing guanidine moiety were successfully synthesized by cyclizatian of free N-monosubstituted guanidines with α,β-unsaturated ketones in tertiary butanol at 25°C. These products are the first examples to be isolated as pure compounds which are unstable in protic solvents such as water, methanol and ethanol. However they are stable in solid states or in aprotic solvents such as dimethyl sulfoxide, dimethyl formamide, pyridine and chloroform.

■ Some Aspects for 1,3-Dipolar Cycloaddition Reaction of Nitrile Oxide with Methyl Crotonate in the Synthesis of Carbapenam Antibiotics

Tetsuji Kametani,* Atsushi Nakayama, Yoshito Nakayama, Tsuneko Ikuta, Rumiko Kubo, Eiko Goto, Toshio Honda, and Keiichiro Fukumoto

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

1,3-Dipolar cycloaddition reaction of the nitrile oxides, generated in situ from the nitro compounds (6~9) and phenyl isocyanate, with methyl crotonate afforded the corresponding isoxazolines (10~17) in moderate yields. Hydrogenation of 12, 14 and 16 on platinum oxide gave the amino esters (18 and 20) and the lactam (22), respectively. The amino esters (18 and 20) were converted to the β-lactams (23~26) with ethylmagnesium bromide in tetrahydrofuran. Finally, 3,4-bond formation reaction for the mesyloxy derivative (27) of 24 furnished the carbapenam derivative (28) in good yield.

■ Total Synthesis of (±)-Epithienamycins A and B [(±)-Olivanic Acids NM22380 and 22382]

Tetsuji Kametani,* Shyh-Pyng Huang, Takayasu Nagahara, and Masataka Ihara

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

(±)-3R*-(1’S*-Hydroxyethyl)-4R*-(2’,2’-dimethoxyethyl)-2-azetidinone (6), which was obtained from the 4-methoxycarbonyl-isoxazoline (4) as a major product, was converted into (±)-epi-thienamycins A(2) and B(3) [(±)-olivanic acids MM22380 and 22382] via the carbene insertion reaction. This total synthesis confirms the relative stereochemistry of the natural antibiotics.

■ Synthesis of Some New Fluorine Containing 1,3,4-Trisubstituted 4,8-Dihydro-1H-pyraolo[3,4-e][1,4]thiazepin-7(6H)-ones and Related Compounds

Krishna C. Joshi,* Kalpana Dubey, and Anshu Dandia

*Department of Chemistry, University of Rajasthan, Jaipur 302 004, India

Abstract

A series of new fluorine containing 1,3,4-trisubstituted 4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7 (6H)-ones have been synthesized by the condensation of fluorine containing 5-amino-1,3-disubstituted pyrazoles with an appropriate aromatic aldehyde/ketone and mercaptoacetic acid in dry toluene. The reduction of 7-oxo group and the conversion of 7-oxo to 7-thione group have been carried out for the first time in such systems by an elegant procedure.

■ Synthesis of (±)-Rutacridone

Iuliu Mester,* Johannes Reisch, Szuzsa Rózsa, and Kálmán Szendrei

*Institute of Pharmaceutical Chemistry, University of Münster, Hittorfstraße 58-62, D-4400 Münster, Germany

Abstract

(±)-Rutacridone (1) was synthesized by condensation of 1,3-dihydroxy-10-methylacridone (3) with isoprene dibromide. As by-product the linear isomer (±)-isorutacridone (2) was also obtained.

■ New N-Alkylamidomethylation of Electron-rich Carbon in the Hexahydro-1,3,5-triazine — Acetyl Chloride System

Kiyoshi Ikeda,* Toshiaki Morimoto, Yoshiyasu Terao, and Minoru Sekiya

*Shizuoka College of Pharmacy, 2-2-1, Oshika, shizuoka-shi, 442 Shizuoka, Japan

■ Reaction of Halogen with Metal Salts of Pyridinecarboxylic Acid — Decarboxylative Ipso-Substitution

Sakae Uemura,* Sakuya Tanaka, Masaya Okano, and Masatomo Hamana

*Graduate School of Engineering, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan

■ Preparations, Reactions, Abilities of Complexation of Sulfer Compounds Containing Pyridine Nuclei

Hisashi Fujihara, Tsutomu Kawai, Keiko Kishimoto, Satoshi Ogawa, Naomichi Furukawa, and Shigeru Oae*

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

■ Molecular Orbital Study of the Reactivity of Active Alkyl Groups of Pyridine and Pyrimidine Derivatives

Yoshinobu Goto,* Tokihiro Niiya, Takao Sakamoto, Hiroshi Yoshizawa, Hiroshi Yamanaka, and Tanekazu Kubota

*Faculty of Pharmaceutical Sciences, Fukuoka University, Nakamura, Jonan-ku, Fukuoka, 814-0180, Japan

■ Micellar Alignment Effect on the Photodimerization of 2-Pyridones

Takeshi Kato and Yushin Nakamura*

*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

■ Reaction of Aromatic Amine N-Imines Reactivities of Unstable Intermediates Formed in 1,3-Dipolar Cycloaddition and Their Application

Toshihiro Takahashi and Masaaki Hirobe*

*Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan

■ Synthesis of Monocyclic 1,3-Diazepines from Pyridines

Jyoji Kurita,* Hirokazu Kojima, and Takashi Tsuchiya

*School of Pharmacy, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan

■ High-pressure Cycloaddition of Aza-aromatic Compounds

Kiyoshi Matsumoto,* Takane Uchida, Yukio Ikemi, and Morrin Acheson

*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-Nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan

■ The Chemistry of 4-Substituted Indoles

Masanori Somei,* Yoshio Karasawa, Shoichi Tokutake, Toshiya Shoda, Fumio Yamada, and Chikara Kaneko

*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan

■ Total Synthesis of Chanoclavine I

Hitoshi Ishida* and Alan P. Kozikowski

*Shizuoka College of Pharmacy, 2-2-1, Oshika, shizuoka-shi, 442 Shizuoka, Japan

■ Application of Nitrogen-containing Six-membered Pseudo-base Type Compounds on Organic Synthesis (IV) — Synthesis of Spiro-cyclopropane Ring Compounds from the Reaction with Dichlorocarbene

Yoshiki Hamada* and Michiharu Sugiura

*Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan

■ Reactions of Aromatic N-Oxides with Heterocyclic Active Methylenes in the Presence of Acetic Anhydride

Seitaro Saeki,* Mohammed M. Yousif, Kazuhisa Funakoshi, and Masatomo Hamana

*Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

■ Synthesis of Phosphonates from Heteroaromatic Cations and Their Use in Wittig-Horner Reaction: On Isoquinoline and Quinoline Series

Kin-ya Akiba,* Yoshio Negishi, Katsuyuki Kurumaya, and Naoki Inamoto

*Department of Chemistry, Faculty of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan

■ Syntheses of Isoxazole and Pyrrole Derivatives via O-Acylation of Aliphatic Nitro Compounds

Kazuho Harada,* Eisuke Kaji, and Shonosuke Zen

*School of Pharmaceutical Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo 108-8641, Japan

■ Selective Preparation of Unsymmetric Isoxazole from Enones

Choji Kashima,* Nobutoshi Yoshihara, and Shun-ichi Shirai

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