HETEROCYCLES

■ Contents

■ Crown Compounds Containing a 1,3,4-Thiadiazole Moiety: Microwave Assisted Synthesis, Crystal Structure and Quantum Calculations

Mounim Lebrini, Fouad Bentiss, Hervé Vezin, Jean Pierre Wignacourt, Pascal Roussel, and Michel Lagrenée*

*Laboratory of Cristallochemistry and Physicochemistry of the Solide, CNRS UMR 8012, ENSCL, BP. 90108, F-59652 Villeneuve d’Ascq Cedex, France

Abstract

A number of macrocyclic polyether compounds containing a 2,5-bis(2-hydroxyphenyl)-1,3,4-thiadiazole moiety are quickly prepared by a nucleophilic substitution reaction involving ethylene or polyethyleglycol ditosylate and a biphenol, the 2,5-bis(2-hydroxyphenyl)-1,3,4-thiadiazole, with solid anhydrous carbonate as a base under microwave irradiation. The quantum calculations at DFT level and the structure of different conformations of the 2,5-bis(2-hydroxyphenyl)-1,3,4-thiadiazole were performed both in vacuum and acetonitrile solvent using PCM method. The structures are ascertained by spectroscopic properties. The crystal structure of one of the crown compounds has been determined and shows the sufur atom to be inside the macroring cavity.

■ Reactions of 4-Pentenoic Acid with Sulfenyl Cations Generated Electrochemically from Bisquinolinyl and Bispyridinyl Disulfides

Krzysztof Marciniec, Andrzej Maslankiewicz,* Maria J. Maslankiewicz, and Zbigniew Ciunik

*Department of Organic Chemistry, The Medical University of Silesia, Jagiellonska 4, 41-200 Sosnowiec, Poland

Abstract

Lactonization of 4-pentenoic acid to 5-(azinylthio)methyloxolan-2-ones (8) was performed by addition of electrochemically generated azinylsulfenyl cations starting from the respective 3,3’-bis(pyridinyl or quinolinyl) disulfides (2) or (5) and 4,4’-bis(7-chloroquinolinyl or 3-methylthioquinolinyl) disulfides (6b), (6c) and using a bromide ion as a redox catalyst. Sulfenyl cations generated in the same manner from 2,2’-bispyridinyl and 2,2’-bisquinolinyl disulfides (1) or (4) reacted with 4-pentenoic acid to form thiazolo[3,2-a]pyridinio- or quinoliniopropanoate (9a) or (9b). In the case of 8,8’-bisquinolinyl disulfide (7), oxolan-2-one (8e) was accompanied by 2,3-dihydro-1,4-thiazinequinolinio derivative (10). 4,4’-Bis(pyridinyl nor quinolinyl) disulfides (3) and (6a) did not give such products.

■ Stereoselective Functionalization of Alkenyl-β-lactams

Luigino Troisi,* Emanuela Pindinelli, Luisella De Vitis, Catia Granito, and Ludovico Ronzini

*Department of Sciences and Biological and Environmental Technologies, University of Lecce, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy

Abstract

Alkenyl-β-lactams, obtained by palladium-catalyzed [2+2] cycloaddition of imines with allyl halides, were functionalized in a stereoselective way by a simple deprotonation with LDA, and subsequent capture of the formed carbanion by various electrophiles. Alkyl, hydroxy and epoxy functionalities were inserted exclusively at the C-3 carbon atom of the β-lactamic system, without performing new cyclizations. High stereoselectivity was noticed with the quenching taking place preferentially at the C_α with respect to the C_γ carbon atom of the allylic moiety of the azetidinyl anion generated by deprotonation.

■ Synthesis of Functionalized 5,5-Disubstituted Isoxazolines via 1,3-Dipolar Cycloaddition Reactions of Geminal Disubstituted Alkenes

Ashton T. Hamme, II,* Jianping Xu, Jun Wang, Tiffany Cook, and Erick Ellis

*Department of Chemistry, Jackson State University, Jackson, Mississippi 39217, U.S.A.

Abstract

Regioselective syntheses of functionalized 5,5-disubstituted 2-isoxazolines were achieved through 1,3-dipolar cycloaddition reactions of various aromatic nitrile oxides with geminal disubstituted alkenes.

■ 1-(3-Nitrobenzenesulfonyl)-3,4-dimethylimidazolinium Iodide: A More Active Tetrahydrofolate Coenzyme Model

Yongbin Zhang, Donghong Li, Chizhong Xia, and Wei Guo*

*School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China

Abstract

Reaction of tetrahydrofolate coenzyme model, 1-(3-nitrobenzenesulfonyl)-3,4-dimethylimidazolinium iodide (2) with a series of aromatic amines produced N,N,N’-trisubstituted-2-methylethylenediamine derivatives (3-7). Reaction of the model with indole or carbazole in the presence of NaH provides two imidazolidine derivatives. The action of one-carbon transfer of the model with several bifunctional nucleophiles is also tested.

■ An Enantioselective Synthesis of 1-Azaspiro[5.5]undecane Ring System of Histrionicotoxin Alkaloids from D(+)-Glucose

Smritilekha Bera

*National Chemical Laboratory, Pune 411 008, India

Abstract

The preparation of 1-azaspiro[5.5]undecane ring system common to histrionicotoxin alkaloids has been accomplished from D-glucose diacetonide.

■ Stereochemistry of Fully Acetylated Tetrahydropterins and Tetrahydroquinoxalines

Ning Chen, Kazuhisa Ikemoto, Shingo Komatsu, and Shizuaki Murata*

*Graduate School of Environmental Studies, Nagoya University, Chikusa, Nagoya, 464-8601, Japan

Abstract

Completely acetylated derivatives of naturally occurring tetrahydro-D-monapterin, (6R)-2-acetamido-6-[(1R,2R)-1,2,3-triacetoxypropyl]-5,8-diacetyl-5,6,7,8-tetrahydropteridin-4(3H)-one, show plus and minus CD signs at λ 280 and 240 nm, respectively. Similar CD spectra are obtained on (2S)-1,4-diacetyl-1,2,3,4-tetrahydro-2-isopropylquinoxaline and (2S)-1,4-diacetyl-1,2,3,4-tetrahydro-2-isobutylquinoxaline but not on (2S)-1,4-diacetyl-1,2,3,4-tetrahydro-2-methylquinoxaline nor on the 2-ethyl derivative. The similarity of their CD spectra is represented the same stereogenic structure based on the boat conformation confirmed by X-Ray crystallographic analyses.

■ A New Synthesis of Phenolic 1-Hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines

Motoki Ikeuchi, Miyuki Ikeuchi, Kumiko Inoue, Syuhei Yamamoto, Aiko Yamauchi, and Masaru Kihara*

*Faculty of Pharmaceutical Sciences, University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan

Abstract

7,8-Dihydroxy-1-phenyl- and 1-(3- and 4-hydroxyphenyl)-1-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine derivatives (2a,b) and (3a-c) were synthesized by intramolecular Barbier reaction of N-(2-iodophenethyl)-phenacylamines (5a,b) and (12a-c) with n-C4H9Li as a key reaction step.

■ A Convenient Procedure for the Synthesis of Substituted 4-Methylaminocoumarins

Khadeejh H. A. Al-Zghoul, Kifah S. M. Salih, Mikdad T. Ayoub,* and Mohammad S. Mubarak*

*Chemistry Department, Faculty of Science, University of Jordan, Amman, Jordan

Abstract

3-Bromo-7-methoxy-4-methylcoumarin and 3-bromo-4,7-dimethyl-coumarin give a mixture of the corresponding 3-aminocoumarins and 4-aminomethylcoumarins upon the reaction with a number of secondary amines. In addition, the reaction of 7-methoxy- and 7-methyl-4-bromomethylcoumarins with secondary diamines affords the corresponding N,N`-dicoumarinmethyldiamine.

■ An Efficient Synthesis of New Spiro[indolo-3(1H),2’(3’H)-oxadiazolyl] and 1-(Triazol-4-ylmethyl)isatin Derivatives

Rachid Bouhfid, Nicolas Joly, Mohamed Massoui, Roméo Cecchelli, Vincent Lequart, Patrick Martin,* and El Mokhtar Essassi

*Blood-Brain Barrier Laboratory (EA 2465), IUT of Béthune, University of Artois, BP 819, F-62408 Béthune, France

Abstract

The synthesis and the characterization of new isatin derivatives obtained by 1,3-dipolar cycloaddition reactions on allylisatin and propargylisatin are described. The products thus regiospecifically obtained in good yields bear oxadiazolyles or trizolyles groups, and were characterized by FT-IR spectroscopy, NMR spectroscopy and mass spectrometry.

■ Improvement of Synthetic Pathways to Thalidomide Ester Derivatives

Gaël Mansard, François Estour, Hervé Galons, and Olivier Lafont*

*Pharmacochemistry Laboratory, Department of pharmaceutical organic chemistry, Faculty of Medicine and Pharmacy, 22 Boulevard Gambetta, 76183 Rouen Cedex 1, France

Abstract

Three synthetic approaches to N-substituted Thalidomide prodrugs from (S)-phtaloylglutamic acid, (S)-Boc-glutamic acid or phtaloylglutamic anhydride are described and compared. The most efficient method is a one-pot synthesis which allowed to obtain an ester derivative of Thalidomide with 67 % yield.

■ Formal Synthesis of (±)-Trachelanthamidine

Meng-Yang Chang,* Dong-Ciao Wu, and Nein-Chen Chang

*Department of Applied Chemistry, National University of Kaohsiung, Kaohsiung 811, Taiwan, R.O.C.

Abstract

Base-induced coupling-cyclization stepwise [3+2] annulation of α-sulfonylacetamide with (Z)-2-bromoacrylate yielded the polysubstituted pyroglutamate with three contiguous chiral centers with trans-trans orientation in a one-pot synthesis. The pyrrolizidine skeleton was obtained via the ring-closing metathesis (RCM) method. This facile strategy was used to synthesize (±)-trachelanthamidine.

■ Concise Route to 4,5-Dioxo-4,5-dihydronaphtho[1,2-b]thiophene-2-carboxylates

Kazuhiro Kobayashi,* Satoshi Yamane, Kazuna Miyamoto, Osamu Morikawa, and Hisatoshi Konishi

*Department of Materials Science, Faculty of Engineering, Tottori University, Koyama-minami, Tottori 680-8552, Japan

Abstract

Reactions of 3-acyl-1,2-naphthoquinones with ethyl mercaptoacetate followed by protection of the resulting hydroxyl groups and thiophene ring formation using 1-trimethylsilylimidazole, deprotection with hydrochloric acid, and oxidation with cerium(IV) ammonium nitrate (CAN) gave, in one-pot, the title thienonaphthoquinone derivatives in moderate to good yields.

■ An Efficient Synthetic Route to New Imidazo[1,2-a]pyridines by Cross-Coupling Reactions in Aqueous Medium

Caroline Castera, Maxime D. Crozet, and Patrice Vanelle*

*Laboratory of Pharmaceutical Organic Chemistry (LCOP), UMR CNRS 6517, University of the Méditerranée , Faculty of Pharmacy, 27 Boulevard Jean Moulin, 13385 Marseille cedex 5, France

Abstract

The Suzuki cross-coupling reaction of 6-bromo-3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]pyridine and 6-bromo-3-nitro-2-tosylmethylimidazo[1,2-a]pyridine provided an efficient route to the corresponding 6-aryl- 3-nitro-2-phenylsulfonylmethylimidazo[1,2-a]pyridines and 6-aryl-3-nitro- 2-tosylmethylimidazo[1,2-a]pyridines. The reaction was catalyzed by palladium(0) in aqueous medium.

■ Chemical Modification of the Sugar Moiety of Pyrimidine Nucleosides via a 4’,5’-Epoxyuridine Intermediate

Hideki Takasu, Hironao Sajiki,* and Kosaku Hirota*

*Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan

Abstract

The reaction of 4’,5’-unsaturated nucleoside (5) with m-CPBA provided different products depending on the solvent. 4’,5’-Epoxynucleoside (6) was generated as a key intermediate although 6 was not stable enough to isolate and further reaction progressed. When the reaction was performed in CH₂Cl₂, 2,4’-cyclonucleoside (7) and 4’-ketonucleoside (8) were obtained. On the other hand, 4’-alkoxy derivatives (9 and 11) together with their epimers (10 and 12) were aquired as a mixture by the nucleophilic attack of alcohol.

■ Regiospecific Aryl Nitration of meso-Tetraarylporphyrins: The Directive Effect of para-Substituent

Hong-Liang Zhang, Wei-Min Shi, and Jian Wu*

*Department of Chemistry, Zhejiang University , Hangzhou, 310027, China

Abstract

Regiospecific nitration of single p-substituted tetraphenylporphyrins with excess nitric acid is reported. The directive effects of different p-substituents, including nitro, acetamido and hydroxy groups, were demonstrated. The electron- withdrawing p-nitro group was found to lead to predominant nitration at the neighboring phenyl ring, and the electron-releasing p-acetamido and p-hydroxy groups lead to adjacent nitration at the same phenyl ring.

■ Synthesis of Glycosides Containing Quinazolin-4(3H)-one Ring System

Gamal A. El-Hiti* and Mohamed F. Abdel-Megeed

*Centre for Clean Chemistry, Department of Chemistry, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, U.K.

Abstract

Reactions of various aminoquinazolin-4(3H)-ones with monosaccharides in the presence of a catalytic amount of glacial acetic acid afforded the corresponding N-glycosylamines as a mixture of α- and β-anomers. Acetylation of this mixture gave the corresponding β-glycoside acetates. However, β-glycoside acetates could be obtained directly from reactions of per-O-acetyl-α-D-glucosyl bromides with quinazolin-4(3H)-one derivatives which deacetyalted to the corresponding β-glycosides. A series of S-glycosides have been synthesised from reaction of per-O-acetyl-α-D-glucosyl bromides with quinazolinethiones.