HETEROCYCLES

■ Preface

George Zweifel

*,

■ Preface

Andrew Pelter

*Chemistry Department, University of Swansea, Singleton park, Swansea SA2 8PP, U.K.

■ Profile of Professor H. C. Brown

Ei-ichi Negishi

*,

■ Regioselective Additions to 3-(Oxazolinyl)pyridine with Organolithium Reagents

A. I. Meyers* and Nicholas R. Natale

*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.

Abstract

Organolithium reagents have been found to add to the 4- or 6-position in pyridines depending on the nature of the oxazoline present. Thus, methoxy-containing oxazolines lead to the 4-addition product (>95%), whereas hydroxy-containing oxazolines direct addition to the 6-position in yields as high as 95%.

■ Pyrazolo[1,5-c]pyrimidines from Pyrylium Salts and Amidrazones and Pyridine lmidoyl-N-imides from lmidoyl Chlorides

Alan R. Katritzky* and Alberto Tárraga Tomás

*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-7200, U.S.A.

Abstract

2,4,6-Triphenylpyrylium salts react with unsubstituted amidrazones to give dihydropyrazolo[1,5-c]pyrimidines or salts of pyridine imidoyl-N-imides. Pyridine imidoyl-N-imides are conveniently prepared from N-aminopyridinium and imidoyl chlorides.

■ Catalytic Reduction of 3-(4,4-Dimethyl-5-keto-3-isoxazole)propionic Acid and Its Derivatives

Henry Feuer and Philip C. Scholl*

*Wetherill Laboratory, Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, U.S.A.

Abstract

Catalytic hydrogenation of 3-(4,4-dimethyl-5-keto-3-isoxazole)propionic acid (1) in glacial acetic acid in the presence of 5% palladium on charcoal gives 4-amino-5-methylhexanoic acid (2). Reductions of the corresponding ester, methyl 3-(4,4-dimethyl-5-keto-3-isoxazole)propionate (3) and amide, 3-(4,4-dimethyl-5-keto-3-isoxazole)propionamide (4) afford, however, γ-isopropylbutyrolactam (5). Reductions of 1 and 3 in aqueous acetic acid give 4-keto-5-methylhexanoic acid (6) and methyl 4-keto-5-methylhexanoate (7), respectively. On the other hand amide 4 is converted to 2-hydroxy-5-isopropylidene-Δ¹-pyrroline (8). Compound 8 is also obtained if 4 is reduced in acetic acid containing a small amount of hydrogen chloride.

■ Long Range Interactions in Bicyclic Semidiones Containing Hetero Atoms

Glen A. Russell,* Lourdes L. Herold, and K.-Y. Chang

*Department of Chemistry, Iowa State University, Ames, Iowa 50011, U.S.A.

Abstract

Long range hyperfine splittings are observed for anti hydrogen atoms in the semidiones 4, 8, 9, 11, and 12, but a corresponding spin delocalization by the lone pair of electrons of a nitrogen or phosphorous bridge in 8, 9, 10, 11, 12, or 13 cannot be observed.

■ Unusual Chemical Behavior of 1,2-Dithiaacenaphthene in the Reactions with Dinitrogen Tetraoxide and Aqueous Bromine — In Contrast to the Ordinary Oxidation with Fenton Reagent

Shigeru Oae,* Tatsuya Nabeshima, and Toshikazu Takata

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

Abstract

Unlike open chain disulfides or even cyclic disulfides, which are readily oxidized by N₂O₄ and aqueous bromine to sulfinyl and/or sulfonyl derivatives, 1,2-dithiaacenaphthene is readily nitrated with N₂O₄ and brominated with aqueous bromine at the naphthalene ring. Other oxidants, such as Fenton system: H₂O₂-TiCl₃, gave predominantly 1,2-dithiaacenaphthene 1-oxide as in the oxidation with H₂O₂.

■ Propellanes. LXIV. Preparation of Propellanones from Propellenes by Consecutive Hydroboration and Oxidation

Pnina Ashkenazi* and David Ginsburg

*Department of Chemistry, Israel Institute of Technology, Haifa 32000, Israel

Abstract

Hydroboration and subsequent oxidation of various olefinic propellanes leads to propellanones. The yields are low for diolefinic substrates.

■ Fuziline, a New Alkaloid from the Chinese Drug “Fuzi” (Aconitum carmichae Debx.)

S. W. Pelletier,* Naresh V. Mody, Kottayil I. Varughese, and Chen Szu-Ying

*Department of Medical Chemistry and Pharmacognosy, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, U.S.A.

Abstract

Chemical investigation of the famous Chinese drug “Fuzi” (Aconitum carmichaeli Debx) resulted in the isolation of a new alkaloid, fuziline, along with the known alkaloids, aconitine, hypaconitine, mesaconitine, neoline and songorine. The structure of fuziline (1) has been established by the use of carbon-13 and proton NMR spectroscopy. Subsequently this structure was confirmed by a single-crystal X-ray analysis.

■ Solvent Effects in Conformational Equilibria of Onium Salts

Kwang-Ting Liu, Ernest L. Eliel,* and William Rand Kenan Jr.

*Laboratories of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, U.S.A.

Abstract

The equilibria of the S-methyl group in cis- and trans-S-methyl-4-t-butylthianium salts and of the N-methyl groups in corresponding N-methyl-4-t-butylpiperidinium and N-cis-2,6-trimethylpiperidinium salts have been studied as a function of solvent, concentration and gegenion. The effects of these factors are appreciable, causing variations of up to 0.2 kcal/mol in ΔG° in the thianium and 0.4 kcal/mol in the piperidinium salts. Rationalizations for these effects are provided.

■ Synthetic Macrocyclic Ligands. V. “Crowned” Dinitrophenylazophenols: Dissolving and Colorating Agent of Alkali and Alkaline Earth Metal Salts in Organic Solvents

Kouichi Sugihara, Takahiro Kaneda, and Soichi Misumi*

*The Institute of Scientific and Industrial Research, Osaka University, 8-1. Mihogaoka, Ibaraki, Osaka 567-0047, Japan

Abstract

The complexations of the title compounds with a series of alkali and alkaline earth metal salts were studied under various conditions, e.g., amine, solvent, etc. A solution of azophenol 2₁-pyridine in chloroform displayed a noticeable metal-cation selective coloration for lithium salts of alkali metal salts.

■ Gandharamine: A New Benzylisoquinoline Alkaloid from Berberis baluchistanica

Musa H. Abu Zarga, Ghulam A. Miana, and Maurice Shamma*

*Department of Chemistry, The Pennsylvania State University, York Campus, P1031 Edgecomb Avenue, York, Pennsylvania 17403, U.S.A.

Abstract

Gandharamine (1) is a new quaternary oxobenzylisoquinolinium alkaloid found in Berberis baluchistanica Ahrendt (Berberidaceae), as well as in Thalictrum fendleri Engelm. ex Gray (Ranunculaceae). Its synthesis from dihydrobenzylisoquinoline 4 has been achieved. The only known naturally occurring close analog of gandharamine is N-methylpapaveraldine (7).

■ The Reactions of Benzenediazonium Ions with Some Purines and Pyrimidines

Ming-Hong Hung and Leon M. Stock*

*Department of Chemistry, University of Chicago, 5735 South Ellis Avenue, Chicago, IL 60637, U.S.A.

Abstract

The reactions of certain pyrimidines and purines with benzenediazonium ions in basic solution have been investigated to determine whether the reactions provide triazenes, azo coupling, or phenylation products. Under these conditions, the anion of uracil forms the 5-azo coupling product. No reaction occurs with the anion of uridine or 5’-uridylic acid. A complex mixture of products is obtained with cytosine, but cytidine and 5’-cytidylic acid fail to yield either azo coupling or phenylation products. Xanthine readily undergoes the 8-arylazo coupling reaction. Xanthosine is unreactive. In contrast, inosine yields 8-phenylinosine. Purine itself is converted to 6-phenylpurine. The structure of the product was proved by deuterium labeling experiments. The factors governing the reactivity of these compounds are briefly noted.

■ Facile Synthesis of N-Substituted 1H-Azepine Derivatives

Nagaraj R. Ayyangar,* Ramesh B. Bambal, and Ananda G. Lugade

*National Chemical Laboratory, Dr. Homi Bhabha road, Pune-411 008, India

Abstract

The facile synthesis of N-sulphonyl and N-ethoxycarbonyl substituted 1H-azepines in high yields by the pressure-induced sulphonylnitrene insertion reaction or, in anhydrous solvents, the 1,3-dipolar azide addition reaction with aromatic substrates containing electron-withdrawing substituents (e.g. dimethyl terephthalate) are described. The probable sequences of reactions involved in the two cases have been indicated.

■ Chemistry of 2,2-Dimethyl-1,3-dioxole. Two-carbon Homologation of Carbonyl Compounds to α-Ketoaldehydes and Dihydroxyacetonyl Moieties

Daniel L. Flynn, Lester A. Mitscher,* Tarik Veysoglu, and Zbigniew Wielogorski

*Department of Medicinal Chemistry, Kansas University, Lawrence, Kansas 66045, U.S.A.

Abstract

The lithium salt of 2,2-dimethyl-1,3-dioxole adds readily to aldehydes and ketones to form the blocked dihydroxyacetonyl moiety. Only in favorable cases, however, can deblocking be accomplished without rearrangement. More commonly, acid-catalyzed deblocking leads to concommitant dehydration and results in excellent yields of α-ketoaldehydes rather than substituted dihydroxyacetones.

■ Organoboron Compounds. 400. Boron-Containing Heterocycles from Vinylaminodialkylboranes and Isonitriles

Vladimir Dorokhov, Olga Boldyreva, Alexander Shashkov, and Boris Mikhailov*

*N. D. Zelinsky Institute of Organic Chemistry, Russia Academy of Science, Leninsky Prospekt 47, Moscow 119991, Russia

Abstract

Vinylaminodialkylboranes react with isonitriles to give the (4+1) cycloadducts (5). These adducts undergo thermal anionotropic rearrangements producing the derivatives of 2-amino-1,2-azaboroline (7), for which the reactions of splintering the exo-cyclic B-N bond are characteristic. On action of alcohol-aqueous solution of HCl, the heterocycles (7) turn into their oxygenous analogues - the 2-alkoxy-3H-1,2-oxaborol derivatives (10).

■ Novel Heterocyclic Systems. Part 7. New Species Containing Two Pyridine Rings by Dehydration of 3-Hydroxy-2(1H)-pyridone Using Phosphorus Pentoxide.

Ian Matthews, Keith Smith,* and Jhon R. Turner

*Department of Chemistry, University College of Swansea, Singleton Park, Swansea SA2 8PP, U.K.

Abstract

Dimeric dehydration products of 3-hydroxy-2(1H)-pyridone (1) are obtained by melting a mixture of (1) and P₂O₅ at 250-290°C. The major product is 3-hydroxy-1-(3-hydroxy-2-pyridyl)-2(1H)-pyridone (7). Also obtained are 1,6-diazaphenodioxin (5) and a novel betaine, 6-oxidodipyrido[2,1-b:2’,3’-d]oxazolium (6).

■ Novel Complexes of Amides and Other Species with a Heterocyclic Boron Betaine

Andrew S. Fletcher, Walter E. Paget, and Keith Smith*

*Department of Chemistry, University College of Swansea, Singleton Park, Swansea SA2 8PP, U.K.

Abstract

The heterocyclic boron-containing betaine (1) forms stable 1:1 addition complexes with water, amines and, more surprisingly, simple amides.

■ A Novel Synthesis of Symmetric Ketones by the Reaction of Organoboranes with Catechol Dichloromethylene Ether in the Presence of Methyllithium

Taihei Kawaguchi, Masahiro Ishidoya, and Akira Suzuki*

*Faculty of Engineering, Hokkaido University, Kita 13 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0828, Japan

Abstract

Organoboranes readily available from alkenes via hydroboration react with catechol dichloromethylene ether in the presence of methyllithium followed by the usual alkaline hydrogen peroxide oxidation to give corresponding symmetric ketones in good yields.

■ A Regiospecific Synthesis of Carbosubstituted Heteroaromatic Derivatives via Pd-Catalyzed Cross Coupling

Ei-ichi Negishi,* Fen-Tair Luo, Roger Frisbee, and Hajime Matsushita

*Wetherill Laboratory, Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, U.S.A.

Abstract

The Pd-catalyzed cross-coupling reaction of either heteroarylzinc derivatives with unsaturated organic halides or heteroaryl halides with organometallic reagents containing Zn or Al can produce cleanly and regiospecifically the corresponding carbo-substituted heteroaromatic compounds in high yields.

■ Bis(benzo-1,3-dithiafulvenyl)

Tokuzo Kawase, Hiroshi Awaji, Shigeo Yoneda, and Zen-ichi Yoshida*

*Department of Synthetic Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan

Abstract

Bis(benzo-1,3-dithiafulvenyl) (3) is newly prepared in three steps from o-benzenedithiol and 2,5-dimethoxytetrahydrofuran, and the cyclic voltammogram shows the excellent electron-donating property of 3.

■ Protonation Induced Carbon-13 NMR Shifts in Protonated Cyclic Amines

Mariappan Periasamy*

*Wetherill Laboratory, Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, U.S.A.

Abstract

Protonation induced Carbon-13 NMR chemical shifts are measured for five cyclic amines (1-5). The effect of sp³ hybridized positive charge on the chemical shifts of remote carbon atoms in protonated cyclic amines is compared with the effect of sp² hybridized positive charge on the chemical shifts of remote carbon atoms in arylcyclic carbocations.

■ Improved Procedure for Lithium Borohydride Reduction of Cyclic Anhydrides to Lactones in Tetrahydrofuran

Srinivasan Narasimhan*

*Wetherill Laboratory, Purdue University, West Lafayette, Indiana 47907, U.S.A.

Abstract

The rate of reduction of several cyclic anhydrides by lithium borohydride in tetrahydrofuran at 25°C has been studied. The reaction has been utilized for the rapid and selective conversion of cyclic anhydrides to lactones.

■ Synthesis and Properties of Derivatives of Cyclopenta[b]pyran and Cyclopenta[b]thiapyran Isoelectronic with Azulene

Masahiko Iyoda, Yoshio Aso, and Masazumi Nakagawa*

*Department of Chemistry, Faculty of Science, Osaka University, Toyonaka, Osaka 560-8531, Japan

Abstract

Cyclopenta[b]pyran and cyclopenta[b]thiapyran derivatives isoelectronic with azulene have been synthesized by intramolecular cyclization of substituted octadienyne-dials. The cyclization reaction of octadienyne-dials proceeds regiospecifically and the formation of cyclopenta[b]pyrans and/or cyclopenta[b]thiapyrans depends on a subtle variety of the reaction conditions.

■ Quinuclidin-4-yl Anion. Generation and Stability Comparison by Radical Anion Reduction

Shelton Bank* and William K. S. Cleveland

*Department of Chemistry, State University of New York at Albany, Albany, New york 12222, U.S.A.

Abstract

Radical anion reduction of 4-bromoquinuclidine and 1-bromobicyclo[2.2.2]octane leads to similar product distributions. The lone pair of electrons on the nitrogen atom in the heterocyclic compound do not affect the anion stability.

■ Synthesis of Naturally Occurring (R)-(+)-Muscopyridine

Kiitiro Utimoto,* Sadao Kato, Michio Tanaka, Yukihisa Hoshino, Sadao Fujikura, and Hitosi Nozaki

*Department of Industrial Chemistry, Faculty of Engineering, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan

Abstract

Incorporation of the chiral center of (R)-4-methyl-5-hexenyl tosylate gives the title compound. The synthesis establishes the absolute configuration of the natural product. The title compound is also obtained from (Z)-1,2-dehydromuscopyridine by asymmetric reduction with chiral alkylboranes.

■ Pheromone Synthesis via Organoboranes: A Stereospecific Synthesis of (E)-7-Alken-1-ols

Deevi Basavaiah*

*Wetherill Laboratory, Purdue University, West Lafayette, Indiana 47907, U.S.A.

Abstract

Borepane, obtained via hydridation of β-chloroborepane, hydroborates 1-bromo-1-alkynes cleanly to provide the β-(cis-1-bromo-1-alkenyl)borepanes. Treatment of these intermediates with sodium methoxide results in the displacement of bromine by one end of the boracycloalkyl moiety, producing the corresponding vinylboranes, containing the eight-membered borocane moiety. These intermediates, on controlled protonolysis followed by oxidation, provide the (E)-7-alken-1-ols. This process constitutes a simple, very convenient, stereospecific and general one-pot synthesis of (E)-7-alken-1-ols. Pheromones, (E)-7-tetradecen-1-ol, (E)-7-tetradecen-1-ol acetate and (E)-7-dodecen-1-ol acetate were prepared in excellent yields.

■ 1,3,2-Benzodioxaborole in Organic Synthesis: Preparation of Vinyl lodides

George W. Kabalka,* Kunda A. R. Sastry, and Vishwanatha Somayaji

*Chemistry Department, University of Tennessee, Knoxville, Tennessee, 37196, U.S.A.

Abstract

1,3,2-Benzodioxaborole readily hydroborates alkynes to form vinylboronic esters. The esters can be hydrolyzed to the corresponding vinylboronic acids which react with sodium iodide and chloramine-T to form isomerically pure (E)-iodoalkenes.

■ Cleavage of Cyclic Ethers with Boron Bromide. A Convenient Route to the Bromosubstituted Alcohols, Aldehydes and Ketones

Surendra U. Kulkarni* and Vemanna D. Patil

*Wetherill Laboratory, Purdue University, West Lafayette, Indiana 47907, U.S.A.

Abstract

Cyclic ethers are readily cleaved by BBr₃ under mild conditions, providing the corresponding ω-bromoalkylborates (1). Redistribution of 1 with methanol affords ω-bromoalcohols (2). Oxidation of 1 with pyridinium chlorochromate forms the corresponding ω-bromoaldehydes (3). Under these conditions, epoxides yield first the borates of the corresponding bromohydrins, with subsequent oxidation of the intermediate (without isolation), giving the α-bromoketones in high purity and satisfactory yield.