HETEROCYCLES

■ Contents

■ Regioselective Synthesis of 1-Benzyl- and 1-Methyl-4-vinylimidazole and Their Reactions with N-Phenylmaleimide

Carl J. Lovely,* Hongwang Du, and H. V. Rasika Dias

*Department of Chemistry and Biochemistry, The University of Texas at Arlington, 502 Yates Street, Arlington, TX 76019, U. S. A.

Abstract

The regioselective synthesis of 1-benzyl- and 1-methyl-4-vinylimidazole from 4,5-diiodoimidazole is described. Their Diels-Alder reactions with N-phenylmaleimide provide a variety of adducts, including the anticipated enamine and the corresponding aromatized isomer. However, additional products including ene adducts, a bis Diels-Alder adduct and oxidation products were isolated.

■ Palladium-catalyzed Asymmetric Allylic Alkylation Using Chiral Prolinol-derived Aminophosphine Ligands

Takashi Mino,* Youichi Tanaka, Koji Akita, Masami Sakamoto, and Tsutomu Fujita

*Chiba University, Faculty of Engineering, Department of Materials Technology, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (4) with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of a new chiral prolinol-derived aminophosphine ligand (3e) in good yield with good enantioselectivity (up to 96% ee).

■ Electrolytic Partial Fluorination of Organic Compounds. 66. Anodic Fluorination of (Thiazol-2-yl)acetonitriles

Sayed M. Riyadh and Toshio Fuchigami*

*Department of Electronic Chemistry, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan

Abstract

Electrochemical partial fluorination of (4-arylthiazol-2-yl)acetonitriles was carried out to afford the corresponding (4-aryl-5-fluoro-5H-thiazol-2-ylidene)acetonitriles as main products in addition to (4-aryl-5-fluorothiazol-2-yl)acetonitriles and (4-arylthiazol-2-yl)fluoroacetonitriles. AM1 calculations were conducted to compare the stability of the fluorinated products.

■ One-Pot Synthesis of Macrocyclic Dioxatetralactones from the Sequential Inter- and Intramolecular [2+2] Photocycloaddition Reactions

Tetsuro Shimo, Makoto Kawamura, Eriko Fukushima, Mikio Yasutake, Teruo Shinmyozu, and Kenichi Somekawa*

*Kagoshima University, Faculty of Engineering, Department of Applied Chemistry, Korimoto, Kagoshima 890, Japan

Abstract

Sensitized photocycloaddition reactions of polymethylenedioxy-di-2-
pyrones (1 - 3) with ethylene diacrylate (4a) afforded macrocyclic dioxatetralactones (6a - 8a) having sixteen- to eighteen-membered rings. Similar reaction of 1 with ethylene dimethacrylate (4b) afforded similar lactones (6b) and (9). The stereochemical features of 6a and 7a depending on the chain length elucidated by the X-Ray crystal analysis are figured by MOPAC conformational analysis of the reactants (1, 2 and 4a).

■ The Palladium-catalyzed Cross-coupling reactions of 3-Chloro-4-halogeno-1,2,5-thiadiazoles

Alain Merschaert* and Hugo J. Gorissen

*Lilly Research Laboratories, Chemical Process R & D, Lilly Development Centre S. A., B-1348 Mont-Saint-Guibert, Belgium

Abstract

3,4-Dichloro- and 3-chloro-4-halogeno-1,2,5-thiadiazoles (halogeno-: bromo- and iodo-) are involved in Pd-catalyzed cross-coupling reactions under Stille and Suzuki conditions. As a result, by using the commercially available 3,4-dichloro-1,2,5-thiadiazole as substrate, several 3-alkyl-, 3-alkenyl-, 3-alkynyl- and 3-aryl-4-chloro-1,2,5-thiadiazoles can easily be prepared. However, these reactions through direct desymmetrization of the 3,4-dichloro-1,2,5-thiadiazole always occur with side-reactions resulting from the concurrent decomposition of the heterocyclic ring of the starting material. These problems are resolved by involving, in these Pd-catalyzed cross-coupling reactions, the more reactive and selective 3-bromo-4-chloro- and 3-chloro-4-iodo-1,2,5-thiadiazole. These new dihalogeno-1,2,5-thiadiazoles can easily be prepared, via diazotization reaction followed by halogen substitution, from the 3-amino-4-chloro-1,2,5-thiadiazole.

■ Phosphine-assisted Rearrangement of 4,5-Dihydroxy-1,2-dithianes to 4-Hydroxy-3-mercaptotetrahydrothiophenes

Sang Hyup Lee and Harold Kohn*

*Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, U.S.A.

Abstract

Treatment of 4,5-dihydroxy-1,2-dithianes with trialkylphosphines and triphenylphosphine under neutral and moderately basic conditions led to the efficient and stereospecific production of 4-hydroxy-3-mercaptotetrahydrothiophenes. The reaction is projected to proceed through three successive intramolecular rearrangements.

■ Synthesis of Heterocyclic γ-Amino-α,β-unsaturated Acid Derivatives and Peptide-Heterocycle Hybrids

Antonio Salgado, Enrique Mann, Francisco Sánchez-Sancho, and Bernardo Herradón*

*Instituto de Química Orgánica General, C. S. I. C., Calle Juan de Cierva, 3, 28006 Madrid, Spain

Abstract

The syntheses of the γ-amino-α,β-unsaturated esters [(R)-4, (S)-5, and (±)-6] are reported. The methodology for the preparation of these triannular heterocycles involves two synthetic sequences from N-substituted amino alcohols: a ‘one-pot’ sequential Swern oxidation-Wittig reaction and an intramolecular Heck reaction. The γ-amino-α,β-unsaturated ester [(R)-4] has been used for the synthesis of the peptide-heterocycle hybrids (19-21).

■ Novel Synthesis of Model Dihydroazepine-fused Indolo[2,3-c]quinolines

Adel M. Al-Khashashneh, Mustafa M. El-Abadelah,* and Roland Boese

*Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan

Abstract

A synthetic route involving double Pictet-Spengler condensations at the indolic C-2 and C- 4 positions of a 3-diaminophenylindole (8) is described leading to a novel dihydroazepine-fused indoloquinoline system. MS and NMR spectral data are in accordance with the assigned pentacyclic structures namely, 7,8-dihydro-1,12-iminobenzo[c]pyrido[4,3,2-ef][1]benzazepines (9a,b), as con-firmed by X-Ray measurements.

■ ¹H NMR Spectroscopy and Conformational Analysis of N-Benzylimidazolidines

Isabel A. Perillo,* Carlos de los Santos, and Alejandra Salerno

*Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 (1113) Buenos Aires, Argentina

Abstract

¹H NMR spectra of a series of 1-benzyl- and 1,3-dibenzylimidazolidines are analyzed and correlated with their conformational features. The spectra are assigned on the basis of chemical shifts and proton coupling constant values, and confirmed by NOESY spectra. C₂-Unsubstituted imidazolidines (1, 9) show a fast inversion of the nitrogen atoms. By contrast, 1,2,3-trisubstituted imidazolidines display a preferential conformation with a transoid orientation of the N₁, N₃, and C₂ substituents.

■ Regioselective Reduction of N-Alkyl-3-sulfonyl Glutarimide. Formal Synthesis of 1,2,3,4,6,7,12,12b-Octahydroindolo[2,3-a]quinolizine and Homobaclofen

Meng-Yang Chang and Shui-Tein Chen*

*Institute of Biological Chemistry, Academia Sinica, 128, Yan-Chiu-Yuan Road, Sec II, NanKang, Taipei, 11529, Taiwan, R.O.C.

Abstract

Reduction of N-alkyl-3-sulfonylglutarimides with (1) sodium hydride and then with lithium aluminum hydride, or (2) sodium borohydride yielded two different types of regioselectively reduced hydroxypiperidinones which were further dehydrated to two pyridin-2-ones in the presence of boron trifluoride etherate. Cycloaddition and regioselective reduction were combined to synthesize 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine and homobaclofen.

■ Synthesis and Extraction Propertieis of New Bis-crown Ethers Derived from Stereoisomer of 1,2-Cyclohexanediols for Alkali Metal Cations

Seyed Mohammad Seyedi,* Ali Gouran, and Tahereh Malekshah

*Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, 91775, Iran

Abstract

Stereoisomers of new bis(benzo-15-crown-5) derivatives were synthesized from cis- and trans-1,2-cyclohexanediols. The complexing ability of these bis-crown ethers toward sodium, potassium, lithium, calcium, and magnesium cations has been measured by the solvent extraction method. The extraction data show that the extractabilities of these cations are increased due to the formation of “sandwich-type” complexes by the cis-isomer. The results also show that steric hindrance of substituent on the benzene rings does not have any interference with the formation of a sandwich-type complex in the cis-form.

■ Chlorination and Subsequent Cyclization to 1,3,4-Oxadiazoles of N¹-Acyl-N³-cyanoguanidines and Related Compounds

Takayuki Suyama,* Tadashi Hasegawa, Motokazu Oda, Masahiko Tomaru, and Hiroyuki Ohkoshi

*Kanagawa Institute of Technology, Faculty of Engineering, Department of Applied Chemistry, Shimo-ogino, Atsugi-shi 243-02, Japan

Abstract

N¹-Acyl-, N¹-alkoxycarbonyl-, and N¹-(N,N-dialkylcarbamoyl)guanidines bearing electron-withdrawing cyano or sulfonyl group at the N³-position were found to provide corresponding rearranged products, 1,3,4-oxadiazoles, when these guanidines were chlorinated by sodium hypochlorite followed by treating with base. Assignments of obtained compounds were accomplished by means of some reactions such as acid hydrolysis, alkoholysis, and catalytic hydrogenations, and of MS spectra.

■ Synthesis of Dibenzo[a,f]quinolizinium and 2-Phenyloxazolo[3,2-a]quinolinium Perchlorates via Acid-catalyzed Cyclization of 1-(2-Oxo-2-phenylethyl)quinoline-2(1H)-ones

I-Li Chen, Yeh-Long Chen, Tai-Chi Wang, and Cherng-Chyi Tzeng*

*School of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, 100 Shih Chuen 1st Rd., Kaohsiung 807, Taiwan, R.O.C.

Abstract

Treatment of certain N-alkylated quinolin-2(1H)-ones with concentrated H₂SO₄ afforded oxazolo[3,2-a]quinolin-10-ylium perchlorates via a Z-form enol intermediate while others gave dibenzo[a,f]quinolizinium perchlorates via an E-form enol intermediate. We examined the structure of starting N-alkylated quinolin-2(1H)-ones and found that a methoxy group substituted at R₄ is required for the formation of tetracyclic dibenzo[a,f]quinolizinium perchlorates.

■ A Pseudo Thiacrown Compound Formed by Hydrophobic Interaction of Its Lipophilic Parts in Water: Ag⁺-Selective Fluorophore in Water

Seiichi Inokuma, Susumu Nishio, Takashi Funaki, Norio Atarashi, Tetsuya Shirakawa, and Jun Nishimura*

*Department of Chemistry, Faculty of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu 376-8515, Japan

Abstract

Amphiphilic podand (3) was prepared by conventional thioether synthesis in ethanol. It shows exclusive selectivity toward Ag⁺ ion in a liquid-liquid extraction. It was also found to exhibit selective fluorescence decrease only in the presence of Ag⁺ ion in water. From the fluorometric titration, the complexing stability constant toward Ag⁺ in water estimated to be log K_a = 4.2, which value is comparable to cyclic dithia-18-crown-6. This extraordinarily high value was caused by a pseudo cyclic structure formed in water, which was supported by ¹H NMR spectral analysis.

■ Phosphodiesterase Inhibitory Coumarinolignoids from Duranta repens

Kiran Iqbal, Itrat Anis, Naveen Muhktar, Abdul Malik,* Naheed Fatima, and Muhammad Iqbal Chaudhary

*International Centre for Chemical Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Pakistan

Abstract

Durantins A-C (1-3), new coumarinolignoids together with three known compounds cleomiscosins A (4), 6,7,8-trimethoxycoumarin (5) and 5,4’-dihydroxy-3,6,7-trimethoxyflavone (6) have been isolated from a CHCl₃ soluble fraction of Duranta repens. Their structures were assigned on the basis of spectral studies. Compounds (1, 3 and 4) showed inhibitory activity against phosphodiesterase enzyme.

■ Six Flavonostilbenes from Gnetum afircanum and Gnetum gnemon

Ibrahim Iliya, Toshiyuki Tanaka,* Zulfiqar Ali, Munekazu Iinuma, Miyuki Furusawa, Ken-ichi Nakaya, Yoshiaki Shirataki, Jin Murata, Dedy Darnaedi, Nobuyasu Matsuura, and Makoto Ubukata

*Gifu Prefectrual Institute of Health and Environmental Sciences, 1-1 Nakafudogaoka, Kakamigahara, Gifu 504-0838, Japan

Abstract

Six new flavonostilbenes (gnetoflavanols A, B, C, D, E and F) were isolated from the stem of Gnetum africanum and the root of G. gnemon. The structures of the compounds were determined by spectroscopic analysis. The antioxidant activity of the compounds on lipid peroxide inhibition and superoxide scavenging activity were also investigated.

■ An Easy Method for the N-Alkylation of Amides, Carbamates, Ureas and Azoles. Reactivity of 4-Chloromethylpyrazoles with Weak Nucleophiles under Neutral Conditions

Mayoral Elena Pérez and Ballesteros Paloma

*Departamento de Química Orgánica y Biologiá, Faclutade de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain

Abstract

4-Chloromethylpyrazoles are shown to react readily with amides, carbamates, ureas and azoles under neutral conditions giving the corresponding N-monoalkylated derivatives with moderate yields. Alkylation of alcohols and thiols occurs under the same conditions. The procedure described may provide a convenient and easy method for the introduction of a 4-pyrazolylmethyl group into molecules containing functional groups with weak nucleophilic character.

■ Anticoccidial Activity of Some Azacyclo Organoborinates

Hitoshi Tabuchi, Harumoto Kawaguchi, Hisashi Taniguchi, Hideyuki Imazaki, and Yoshio Hayase*

*Aburahi Laboratories, Shionogi & Co. Ltd., Gotanda, Koka-cho, Koka-gun, Shiga 520-3423, Japan

Abstract

A series of new azacyclo organoborinates derivatives of piperidinyl and pyridinyl alcohols with anticoccidial activity in vivo assay system in battery trials are described. Parameters of anticoccidial efficacy that were evaluated were body weight, lesion scores and number of oocysts. Among them, di(4-chlorophenyl)(2-piperidinylmethoxy-O,N)boron, and di(3-trifluoromethyl-phenyl)(2-pyridinylethoxy-O,N)boron showed good anticoccidial activity against both of the important parasite, Eimeria tenella and Eimeria acervulina

■ A Review on 2-Heteryl- and Heteroalkyl 4(3H)-quinazolinones

Padala Satyanarayana Reddy,* Padi Pratap Reddy, and Thipireddy Vasantha

*Department of Chemistry, Osmania University, Hyderabad 500 007, India

Abstract

Recent progress in the synthesis and pharmacological activity of 2-heteryl / heteroalkyl-4(3H)-quinazolinones is reviewed.