HETEROCYCLES

■ Contents

■ Synthesis of Nitrogen Heterocycles Utilizing Molecular Nitrogen as a Nitrogen Source and Attempt to Use Air Instead of Nitrogen Gas

Miwako Mori*

*Health Sciences University of Hokkaido, Ishikari-Tobetsu 061-0293, Japan

Abstract

Nitrogen fixation using transition metals is a challenging subject. Using a titanium-nitrogen complex, discovered by Yamamoto in 1967, and titanium isocyanate complex, molecular nitrogen could be incorporated into organic compounds to afford various heterocyclic compounds. Furthermore, novel titanium-catalyzed nitrogenation procedure was developed. That is, a THF solution of TiCl₄ or Ti(OⁱPr)₄, and an excess amount of Li and TMSCl was stirred under nitrogen (1 atm) at room temperature overnight and to this solution was added phthalic anhydride. The whole solution was refluxed overnight to afford a phthalimide in over 100 % yield. Using the stoichiometric conditions of the novel nitrogenation, various indole, pyrrole, pyrrolizine, indolizine derivatives and lactams were obtained in good to moderate yields after usual workup. Although the structure of the titanium-nitrogen complex has not been determined yet, the complex is thought to be a mixture of N(TMS)₃, TiX₂N(TMS)₂ and XTi=NTMS. Nitrogen in air could be directly fixed using this method, and the natural products, such as monomoline I, lycopodine and pumiliotoxin C, could be synthesized from nitrogen in air as a nitrogen source.

■ First Formation of Thiepino[2,3-b]- and Thiepino[3,2-a]indolizine Derivatives

Hidetoshi Isawa, Hiroyuki Suga, and Akikazu Kakehi*

*Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, Wakasato, Nagano 380-8553, Japan

Abstract

The reactions of potassium 1,3-bis(ethoxycarbonyl)indolizine-2-thiolates with ethyl 4-bromocrotonate afforded the corresponding indolizine derivatives having (E)-(3-ethoxycarbonyl-2-propenyl)thio, (E)- and (Z)-(3-ethoxycarbonyl-1-propenyl)thio group at the 2-position. The alkaline treatment of these S-alkylated indolizines gave the title compounds in good yields.

■ Effect of a Metal Salt on Thiiranation of 2’-Adamantylidene-9-benzonorbornenylidene with 4,4’-Dithiodimorpholine and Acetic Anhydride

Yoshiaki Sugihara,* Hiroki Koyama, and Juzo Nakayama*

*Department of Chemistry, Graduate School of Science and Engineering, Saitama University, Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan

Abstract

Using a solution of a metal salt, it was possible to decrease the quantity of Ac₂O used in the thiiranation of 2’-adamantylidene-9-benzonorbornenylidene 1 with 4,4’-dithiodimorpholine 4 and Ac₂O. Thiiranation in a 0.1 M Et₂O solution of LiClO₄ at -15 °C afforded thiiranes 2 and 3 in moderate yields without the decomposition of the thermally less stable 3.

■ Synthesis and Thermal Decomposition of Thiirane 1-Imides of 2’-Adamantylidene-9-benzonorbornenylidene

Yoshiaki Sugihara,* Ayumi Kobiki, and Juzo Nakayama*

*Department of Chemistry, Graduate School of Science and Engineering, Saitama University, Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan

Abstract

Two isolable thiirane 1-imides 21 and 22 were synthesized successfully by imination of anti- and syn-2’-adamantylidene-9-benzonorbornenylidene sulfides 19 and 20 with Chloramine T in CH₂Cl₂ and MeCN at -18 °C. Thermal decompositions of 21 and 22 in solution at room temperature or in the solid state on heating gave mainly 19, alkene 23, and aziridine 24.

■ Synthesis of Tetra- and Penta-heterocyclic Compounds Incorporated Isoquinoline Moiety

Tayseer A. Abdallah,* Hamdi M. Hassaneen, and Hayam A. Abdelhadi

*Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Abstract

7-Amino-2,3-dimethoxy-9-phenyl-5,6,9,6a-tetrahydropyridino[2,1-a]isoquinoline-8,10-dicarbonitrile 5 was prepared via Michael addition reaction of benzylidenemalononitrile 2 with isoquinoline-1-carbonitrile 1. Reaction of 5 with triethyl orthoformate and formamide led to the formation of the corresponding 4-ethoxymethylene and 4-aminopyrimidine derivatives of benzo[a]quinolizines 6 and 7, respectively. Compound 6 reacted with hydrazine to give imino-amino compound 8. The latter compound reacted with formic acid, triethy1 orthoformate, acetic anhydride or benzoy1 chloride to give the triazolopyrimidine derivatives 9, 10 and 11, respectively. Compound 8 reacted with hydrazonoy1 halides 12, 13 and diethy1 oxalate to give triazinopyrimidine and triazolopyrimidine derivatives 16, 17 and 20, respectively.

■ Transformations of 3-(1-Aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione with Hydrazines

Konstantin V. Shcherbakov, Yanina V. Burgart, and Victor I. Saloutin*

*I. Ya. Postovski Institute of Organic Synthesis of Urals Division of Russian Academy of Sciences, 22/20, S. Kovalevskoi / Akademicheskaya Str., Ekaterinburg, GSP-147, 620041 Russia

Abstract

3-(1-Aminoethylidene)-5,6,7,8-tetrafluorobenzopyran-2,4-dione reacts with the substituted hydrazines depending on hydrazine nucleophilicity and the reaction conditions. 3-R-hydrazinoethylidene-5,6,7,8-tetrafluorobenzopyrandiones are formed as a result of the transamination at aminoethylidene fragment by hydrazine NH₂-group. In the case of methylhydrazine and hydrazine the transamination can be accompanied by the substitution of fluorine atom at the atom C-7. Benzopyrano[2,3-c]pyrazolone derivatives are produced due to the intramolecular addition of the RNH-group at the C-2 atom followed by the intramolecular substitution of fluorine atom by hydroxyl group.

■ Synthesis of 2,4,5-Triaryl-5H-chromeno[4,3-b]pyridines in Ionic Liquid

Hui Wu,* Yu Wan, Xiu-mei Chen, Lei-lei Lu, Yang Shen, Cai-fa Chen, Hai-qiang Xin, Hua-hong Xu, Li-ling Pang, Rui Ma, and Cai-hui Yue

*School of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou, 221116, P. R. China

Abstract

The synthesis of 2,4,5-triaryl-5H-chromeno[4,3-b]pyridines via a three-component one-pot cascade reaction of 2-hydroxyacetophenone, aromatic aldehyde and ammonium acetate in ionic liquid [BMIM][BF₄] was reported.

■ Studies on the Amino-Heck Reactions of Unsaturated Ketones O-Phosphinyloximes for the Preparation of Substituted Pyridines

Jia-Liang Zhu,* Yi-Lin Su, Yu-Hui Chan, I-Chia Chen, and Chuan-Chen Liao

*Department of Chemistry, National Dong-Hwa University, Hualien 974, Taiwan, R.O.C.

Abstract

The amino-Heck cyclization process has been applied into a range of γ,δ-unsaturated ketone O-diethylphosphinyloximes 1 and δ,ε-unsaturated ketone O-diethylphosphinyloximes 7. Under the specific catalytic conditions developed by us, these substrates were found to preferentially undergo the 6-endo cyclization to give the formation of 2-substituted pyridines 3 and substituted methylpyridines 8, respectively, in moderate to good yields. Besides, several interesting aspects on the effects of phosphinyl groups, solvents, bases and molecular sieves on the regioselectivity of the cyclization of 1 have also been realized.

■ Chemistry of the Pseudobasic Amino Alcohols. Part 40. Synthesis of Three New Condensed Nitrogen Heterocyclic Systems

Dezso Korbonits,* Benjamin Podányi, Árpád Illár, Kálmán Simon, Miklós Hanusz, and István Hermecz

*Chinoin Ltd, Tó utca 1-5, H-1045 Budapest, Hungary

Abstract

Replacement of the central oxygen atom of the heptacyclic condensed diisoquinoline 3 by reaction with hydrazine, hydroxylamine or thiourea in a simple method gave three new heterocyclic ring systems involving 1,2,4,5- tetrazine (7), 1,2,4,5-oxatriazine (8) and 1,2,4,6-tetrazepine (9) central rings.

■ Synthesis of Unusual Naphtho[2,1-b]furans and Novel 1H-Benz[e]indolinones via Selective Intramolecular Cyclization

Zhi-qi Cong and Hiroshi Nishino*

*Department of Chemistry, Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1, Kumamoto 860-8555, Japan

Abstract

The 2-(2-methoxy-1-naphthyl)-3-oxobutanamides were treated with concentrated hydrochloric acid in acetic acid at room temperature to exclusively give the unusual 5-chloronaphtho[2,1-b]furans in moderate to excellent yields. The same reaction was carried out in ethylene glycol at 80 °C to selectively produce the novel 1H-benz[e]indolinones in good yields. The characterization of the products and the reaction pathway of the selective intramolecular cyclization were discussed.

■ One-Pot Three Component Reaction for the Synthesis of 2-Alkylthio-3-aroylimidazo[2,1-a]isoquinoline in Aqueous Media

Ebrahim Kianmehr,* Reza Faramarzi, and Hamid Estiri

*School of Chemistry, University College of Science, University of Tehran, P.O. Box 14155-6455 Tehran, Iran

Abstract

A one-pot, three component reaction between isoquinoline, phenacyl bromide derivatives and thiocyanates leading to imidazo[2,1-a]isoquinoline derivatives in good yields is reported. Reactions are carried out in water or DMF as the solvent at reflux.

■ NMR Studies of 2-Aryl Derivatives of Benzimidazole, Benzimidazolium Ion, and Benzimidazoline

Chang Kiu Lee and In-Sook Han Lee*

*Department of Chemistry, Kangwon National University, Chuncheon 200-701, S. Korea

Abstract

A series of 2-arylbenzimidazoles, 2-aryl-1,3-dimethylbenzimidazolium iodides, and 2-aryl-1,3-dimethylbenzimidazolines were prepared and their NMR spectra were examined. The substituent parameters were calculated for 2-benzimidazolyl, 2-benzimidazoliumyl, and 2-benzimidazolinyl groups on the chemical shifts of the protons and the carbons of benzene ring. The 2-benzimidazoliumyl group was found to cause a significant up-field shift of the ipso-carbon signal and down-field shift for the ortho- and para-carbon signals. On the other hand, the 2-benzimidazolyl and the 2-benzimidazolinyl groups cause down-field shift of the ipso-carbon signals but cause almost negligible change on the other carbon signals.

■ Synthesis of Fluoroalkylated Dihydroazolo[1,5-a]pyrimidines and Their Ring-Chain Isomerism

Marina V. Goryaeva,* Yanina V. Burgart, Victor I. Saloutin, Elena V. Sadchikova, and Evgeny N. Ulomskii

*I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, Ekaterinburg, 620041, Russia

Abstract

Cyclisation of ethyl 2-ethoxymethylidene-3-polyfluoroalkyl-3-oxo-propionates with 3-amino-1H-[1,2,4]triazole, 3-amino-5-methylpyrazole, ethyl 3-aminopyrazole-4-carboxylate and ethyl 5-aminoimidazole-4-carboxylate hydrochloride results in the formation of polyfluoroalkylated dihydroazolo[1,5-a]pyrimidines. The latter are subject to ring-chain isomerisation in solutions depending on the solvent and the “length” of the fluoroalkyl substituent to yield ethyl 3-polyfluoroalkyl-3-oxo-2-[(azol-3-yl)aminomethylidene]propionates via opening of the heterocycle at the C-N bond. Dehydration of dihydroazolo[1,5-a]pyrimidine were realized.

■ One-Pot Synthesis of 2-Imino-1,3-oxaselenolanes by Reaction of Isoselenocyanates with 2-Bromoethanol

Yosuke Toyoda, Dinesh R. Garud, and Mamoru Koketsu*

*Division of Instrumental Analysis, Life Science Research Center, Gifu University, 1-1 Yanagito, Gifu, Gifu 501-1193, Japan

Abstract

One-pot synthesis of 2-imino-1,3-oxaselenolanes has been achieved by reactions of isoselenocyanates with 2-bromoethanol in good to excellent yields. The structure of the 2-imino-1,3-oxaselenolanes was confirmed by spectroscopic and X-ray analysis. The thermal rearrangement of 2-imino-1,3-oxaselenolanes to 1,3-selenazolidin-2-one is observed for the first time.

■ Synthesis of Cyclopenteno[c] Fused 2,2’-Bipyridine Based Cyclophane by Ring-Closing Metathesis (RCM)

Justyna Lawecka, Danuta Branowska, Zbigniew Karczmarzyk, and Andrzej Rykowski*

*Department of Chemistry University of Podlasie, 08-110 Siedlce, Poland

Abstract

A route to cyclophane 7 incorporating mixed 2,2’-bipyridine 3, consisting of the two different heterocyclic units, i.e. uncondensed pyridine and cyclopenta[c]pyridine, using as a crucial step ring-closing metathesis is reported.

■ One-Pot Synthesis of Alkoxyamine Derivatives by Reductive Alkoxyamination with a 2-Picoline-Borane Complex

Yasushi Kawase, Takehiro Yamagishi, Tero Kutsuma, Kimio Ueda, Takeo Iwakuma, Tadashi Nakata, and Tsutomu Yokomatsu*

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

Abstract

Reduction of oxime ethers with a 2-picoline-borane complex was examined to give alkoxyamine derivatives. The reduction was found to proceed in the presence of aqueous HCl in MeOH-AcOH. The method was extended to one-pot synthesis of alkoxyamine derivatives from aldehydes and ketones. The reaction of carbonyl compounds with alkoxyamines in MeOH-AcOH (10:1), followed by sequential treatment with 2-picoline-borane and 3M HCl afforded alkoxyamine derivatives in good yields. This procedure can be applied to the synthesis of various alkoxyamine derivatives from aliphatic/aromatic aldehydes and ketones.

■ Regio- and Stereoselective Ring-Opening Reaction of Chiral Aziridines: A Facile Synthesis of Chiral β-Amino Alcohols

Kimio Higashiyama,* Masataka Matsumura, Hiroshi Kojima, and Takayasu Yamauchi

*Institute of Medicinal Chemistry; Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

The reaction of chiral 2-alkylsubstituted aziridines (1a-d) with acetic acid afforded β-amino alcohols with an (S)-chiral center at the β position (with respect to oxygen). In contrast, a reaction of the same chiral aziridines with acetyl chloride followed by treatment with water gave β-amino alcohols that have an (S)-chiral center at the α position. In addition, the reaction of the same chiral aziridines with benzyl bromide followed by treatment with 2% sulfuric acid gave the β-amino alcohols with an (R)-chiral center at the α position. Thus, we could control the regioselectivity and stereoselectivity of the ring-opening reaction of chiral aziridines (1a-d).

■ An Efficient Protocol for the Friediänder Synthesis of Quinolines Using the Lewis Acidic Ionic Liquid Choline Chloride·2ZNCL₂

Huey-Min Wang,* Rei-Sheu Hou, Hui-Ting Cheng, and Ling-Ching Chen*

*Graduate Institute of Pharmaceutical Sciences, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.

Abstract

Lewis acidic ionic liquid choline chlorideÅE2ZnCl₂ is shown to be for the first time an excellent solvent and efficient catalyst for the synthesis of quinolines via Friedländer annulation under mild conditions.