HETEROCYCLES

■ The C(2) Stereochemistry of Iboluteine

Ernest Wenkert* and Hugo E. Gottlieb

*Department of Chemistry, Rice University, Houston, Texas 77251, U.S.A.

Abstract

All carbon shifts of iboluteine and its hydroxyindoline and indoline reduction products have been assigned. A lanthanide shift study revealed a R configuration for the spiro carbon of these substances.

■ Synthesis of 4-Aryl-2-picolines

Cheng-Hsia Wang* and Jhy-Ming Horng

*Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei, 116, Taiwan, R.O.C.

Abstract

Thirteen 4-aryl-2-picolines were synthesized by the reaction of a pyridine ring formation in yields the reaction of a pyridine ring formation in yields up to 42%. Six of the picolines synthesized were new compounds.

■ Dihydroimidazobenzothiadiazine Dioxides

Richard Friary* and Elijah H. Gold

*Schering Research, 60 Orange Street, Bloomfield, New Jersey 07003, U.S.A.

Abstract

Reductive cyclization of 2-methylthio-1-(2-nitrobenzenesulfonyl)-4,5-dihydroimidazolides gave a series of 1H-2,3-dihydroimidazo[1,2-b][l,2,4]benzothiadiazine 5,5-dioxides, three of which were isomerized by potassium iodide to 3H-1,2-dihydroimidazo[2,1-c][1,2,4]benzothiadiazine 5,5-dioxides.

■ Studies on the Nature of Vitanin B₆ Intermediates

Wayne P. Duncan, Charles B. Rose,* and Gerald O. Dudek

*Department of Chemistry, University of Nevada, Reno, Nevada 89557-0020, U.S.A.

Abstract

The extent of intramolecular hydrogen-bonding of Pyridoxal analogs can be determined by the phenoxyl H chemical shift.

■ Terrein, an Optically Active Prostaglandin Synthon of Fungal Origin. I. Chemical Conversion to a Corey-type Lactone

Lester A. Mitscher,* George W. Clark. III, Gordon Bokelman, Hollis D. H. Showalter, Kunikatsu Shirahata, P. Bryan Hudson, Earl Fager, Norman Wideburg, and R. Jack Theriault

*Department of Medicinal Chemistry, University of Kansas, 4070 Malott Hall, Lawrence, Kansas 66045-2506, U.S.A.

■ Chiroptical Properties of Fluorescamine Condensation Compounds with Chiral Secondary Amines in situ

Voldemar Toome,* Bodge Wegrzynski, and June Dell

*The Department of Chemistry Research, Hoffman-La Roghe Inc., Nutley, New Jersey 07110, U.S.A.

Abstract

Chiral secondary amines react readily with fluorescamine (FLURAM®) to form aminoenone-type chromophores with long wavelength absorption maxima at 300-320 nm. The chiroptical properties of the reaction mixtures reflect the absolute configuration of secondary amines in situ.

■ Regioselectivity of Nitrile Oxide Cycloadditions to Electron-Deficient Dipolarophiles

K. N. Houk,* Yau-Min Chang, Robert W. Strozier, and Pierluigi Caramella

*Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803-1804, U.S.A.

Abstract

Nitrile oxides give predominantly 5-substituted isoxazolines even with very electron-deficient alkene dipolarophiles, but very electron-deficient alkyne dipolarophiles give substantial amounts of 4-substituted isoxazoles. The contrast between nitrones and nitrile oxides, and between alkenes and alkynes, can be explained on the basis of orbital energies and changes in orbital energies upon molecular distortions in the cycloaddition transition States.

■ A Novel Formation of Cyclopropa[c]quinolines from Some 2-Substituted Quinoline N-Oxides

Seitaro Saeki, Haruyoshi Honda, Yoshio Kaku, Kazuhisa Funakoshi, and Masatomo Hamana*

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

Abstract

2-Chloroquinoline N-oxide (1) reacts with ethyl cyanoacetate in the presence of benzoyl chloride and triethylamine to give ethyl 1-cyano-2-oxo-1a,2,3,7b-tetrahydrocyclopropa[c]quinoline-1-carboxylate (2) in 78% yield. The reaction of 2-phenylquinoline N-oxide also affords ethyl 1-cyano-2-phenyl-1a,7b-dihydrocyclopropa[c]quinoline-1-carboxylate though in a lower yield. The reaction of 1 with malonodinitrile gives not a cyclopropaquinoline but 1-benzoyloxy-2-(α,β-dicyanomethylene)-1,2-dihydroquinoline.

■ Hindered Rotation Around Amide OC-N Bonds: Its Energy Dependence on C-N-C Bond Angle

Tadahisa Sato, Yoshimasa Fukazawa, Yutaka Fujise, and Shô Itô*

*Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Compounds 1-5 exhibit the presence of rotamers in their PMR spectra measured at room temperature. After assignment of signals to each rotamer, temperature dependent change of the signal shape was simulated for 3-5 using line-shape method. Activation parameters deduced therefrom contain usually large free energy of activation for all of these compounds compared with the corresponding dimethylamides. This abnormality was ascribed to the additional destabilization in rotational transition states because of the unusually wide C-N-C angle in the cage system.
To support the large free energy of activations, pure rotamer 5A and nearly pure rotamer 5B were isolated by preparative TLC.

■ On the Formation of Bile Pigments from Heme Proteins

Andrew D. Hamilton and David Dolphin*

*Department of Chemisry, University of British Columbia, Vancouver 8, V5T 1W5, Canada

Abstract

It is proposed that the catabolism of heme to biliverdin involves a initial epoxidation of a protein-bound porphyrin at the exposed γ-methine bridge. Rearrangement of the γ- to an α-epoxide follwed by ring opening to a homooxaporphyrin would generate an electron-rich system capable of reacting with molecular oxygen to form a dioxetane. Fragmentation of the dioxetane to a mono formate ester of biliverdin followed by loss of carbon monoxide would give the bile pigment.

■ The Synthesis of Porphyrins via Dipyrromethenes

John B. Paine. III, Chi Kwong Chang, and David Dolphin*

*Department of Chemisry, University of British Columbia, Vancouver 8, V5T 1W5, Canada

Abstract

The Fischer porphyrin synthesis from dipyrromethene precursors has been improved. The same conditions (bromine in refluxing anhydrous formic acid) which give enhanced yields of centrosymmetric porphyrins from 5-bromo-5’-methyl-2,2’-dipyrromethenes also give substantially higher yields of porphyrins derived from readily available 5,5’-dimethyl and 5,5’-dibromodipyrromethenes.

■ Synthetic Studies on β-Lactam Antibiotics. Part 5. A Synthesis of 7β-Acylamino-3-methyl-1-oxadethia-3-cephem-4-carboxylic Acids

Masayuki Narisada,* Hiroshi Onoue, and Wataru Nagata

*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan

Abstract

Chloroazetidinone 10, prepared from 6-APA, was etherified with propargyl alcohol and zinc chloride to a 2:1 mixture of cis- and trans-ethers 18. The separated cis-ether 18 was converted into a keto ylide 21d, which was cyclized by intramolecular Wittig reaction to 3-methyl 1-oxacephalosporin 22. From this compound, four optically active 3-methyl oxacephalosporins 25a-d were prepared. Interestingly all of them except 25d, 1-oxacephalexin, exhibited antibacterial activity as four to eight times high as that of the corresponding cephalo- sporins.

■ Lipophilic (Hydrophobic) Cyclams with Long Alkyl Side-Chains

Iwao Tabushi* and Mariko Fujiyoshi

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

Abstract

One or two long alkyl chains were introduced either on carbon or nitrogen atom of cyclam (1,4,8,11-tetraazacyclotetradecane) via the direct alkylation or the condensation of the alkylmalonate with the tetramine followed by the borane reduction. Long alkyl substituted cyclams thus obtained are sparingly soluble in water and can extract heavy metal ions from aqueous solution to an organic phase.

■ The Beckmann Rearrangement of Bishomocubanone Oximes

Ken-ichi Hirao,* Hidetoshi Miura, and Osamu Yonemitsu

*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

The Beckmann rearrangement of the title compounds gave brendane derivatives (7, 10, 17, 19, 22) through a regiospecific fission of the C₂-C₃ bond and hetero-cage lactams (8, 9) through a concerted rearrangement of intermediates (viii, ix). The product distribution depends on the reaction conditions.

■ Reactions of New Cyclic Sulphur 1,4-Ylide, 9-Cyano-10-methyl-10-thiaanthracene with Electrophiles

Mikio Hori,* Tadashi Katraoka, Hiroshi Shimizu, and Sachio Ohno

*Department of Pharmacognosy, Gifu College of Pharmacy, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan

Abstract

Reaction of 9-cyano-10-methyl-10-thiaanthracene (1) and dimethyl acetylenedicarboxylate gave the novel intramolecular rearrangement products, 9-cyano-9-R-thioxanthenes (2, 3 and 4) besides 9-cyano-9-methylthioxanthene (5) and thioxanthone (6). And also 9-cyano-9-(dicyanomethyl)thioxanthene (12) and others were obtained from the treatment of 1 with tetracyanoethylene.

■ 1,3-Dipolar Cycloaddition Reaction of Aromatic N-Oxide with Hexafluorobutyne-2

Yoshiro Kobayashi,* Itsumaro Kumadaki, and Shomi Fujino

*Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Abstract

Reaction of quinoline and isoquinoline N-oxides with hexafluorobutyne-2 (1) was examined. The former gave 2-(2-quinolyl)-3-trifluoroacetoxy-1,1,1,4,4,4-hexafluoro-2-butene, quinolinium trifluoromethyltrifluoroacetylmethylide, 2-(2,2,2-trifluoroethy1)quinoline and 2,3-bis(trifluoromethyl)furo[3,2-b]quinoline. The latter gave isoquinolinium trifluoroacetylfluorocarbonylmethylide and three pyrrolo[2,1-b]isoquinoline compounds which were probably formed by addition of the primarily formed ylide, isoquinolinium trifluoromethyltrifluoroacetylmethylide, to 1.

■ A Novel Synthesis of 4-Hydroxypyrimidine Derivatives

Edward Grochowski* and Zygmunt Eckstein

*Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O.Box 58, PL-01-224 Warszawa 42, Poland

Abstract

It was found that 2,2,2-trichloroethylidene-N,N’-bis-phenylacetamide derivatives in alcoholic potassium hydroxide undergo a cyclization to give 5-aryl-6-arymethyl-2-dichloromethyl-4-hydroxypyrimidines.

■ Facile Diketopiperazine Formation from Dipeptides Containing α-Aminoisobutyric Acid. Conformational Factors Influencing Cyclisation

Ramakrishnan Nagaraj and Padmanabhan Balaram*

*Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India

Abstract

Diketopiperazines were formed in good yields on deprotection of N-protected dipeptide esters containing α-aminoisobutyric acid residues. Cyclisation is likely to be favoured by conformational constraints introduced by the gem dialkyl groups.

■ Isolation of 1-Methyl-4,5-dibromopyrrole-2-carboxylic Acid and Its 3’-(Hydantoyl)propylamide (Midpacamide) from a Marine Sponge

Lionel Chevolot, Steve Padua, B. N. Ravi, Peter C. Blyth, and Paul J. Scheuer*

*Department of Chemistry, University of Hawaii at Manoa, 2545 Tha Mall, Honolulu, Hawaii 96822-2275, U.S.A.

Abstract

From an unidentified marine sponge collected in the Marshall islands we have isolated 1-methyl-4,5-dibromopyrrole-2-carboxylic acid (III) and its 3’-(hydantoyl)propylarmide, midpacamide (III). The acid was synthesized and the structure of the amide was determined by spectral analysis and by hydrolysis in alkaline and acid media.

■ Synthesis and Ring Expansion of 3-Methyl-3-vinyl-2-dimethylamino-1-azirine

Léon Ghosez,* André Demoulin, Michel Henriet, Etienne Sonveaux, Maurice Van Meerssche, Gabriel Germin, and Jean-Paul Declercq

*Laboratoire de Chimie Organique de Synthése, Université de Louvain, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium

Abstract

The reaction of 1-chloro-1-dimethylamino-2-methylbuta-1,3-diene with NaN₃ gave directly the title 2-amino-1-azirine (I) and molecular nitrogen. (I) thermally rearranged in the vapour phase to give an aminocarbene resulting from C-C bond cleavage. This carbene cyclised to form an aminopyrrole. With dimethylacetylenedicarboxylate, (I) gave a seven-membered heterocycle resulting from C₃-N bond cleavage and cyclisation at the terminal vinylic carbon atom.

■ Reaction of 1,2-Diphenyl-1-azaspiro[2.2]pentane with C,N-Diphenylnitrone

Otohiko Tsuge* and Hiroyuki Watanabe

*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

Abstract

The reaction of 1,2-diphenyl-1-azaspiro[2.2]pentane (1) with C,N-diphenylnitrone (2) has been investigated under various con- ditions. Azaspiropentane 1 reacts with 5 to give the 1:1 adduct 3, tetrahydro-1H-1,3-benzodiazepin-4-one compound 4, and/or its ring opening isomer 5, whose relative yields depended on the nature of solvents employed. The reaction pathways are also described.

■ Entry into the Allene Oxide-Cyclopropanone System via Vinylsilanes. IV. Reaction of Allene Oxides with Cyclopentadiene

Beng Soon Ong and Tak-Hang Chan*

*Department of Chemistry, McGill University, 7 Montreal, Quebec H3A 2K6, Canada

Abstract

Alkyl-substituted allene oxides reacted with cyclopentadiene to give substitution products whereas aryl-substituted allene oxides reacted with cyclopentadiene and related heterocycles to give cycloaddition products. The difference is explained by a facile rearrangement of aryl-substituted allene oxides to cyclopropanones.

■ A Simple Synthesis of 4-Oxazolidinones, 1,3-Oxazin-4-ones and 1,3-Oxazepin-4-ones from Amide Alcohols

Tetsji Kametani,* Kazuo Kigasawa, Mineharu Hiiragi, Nagatoshi Wagatsuma, Toshitaka Kohagizawa, and Hitoshi Inoue

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

Abstract

Acid-catalysed cyclisation of the secondary amides (3) having a hydroxyl group at α,β or γ-position with formaldehyde gave oxazolidine, 1,3-oxazine or 1,3-oxazepine derivatives, respectively.

■ Leucoxylonine and Ocoxylonine — Hexaoxygenated Aporphines from Ocotea leucoxylon

Roshan Ahmad and Michael P. Cava*

*Department of Chemistry, University of Pennsylvania, 231 South 34th Street Philadelphia, PA 19104-6323, U.S.A.

Abstract

Leucoxylonine and ocoxylonine, two aporphine alkaloids isolated from Ocotea leucowlon (Lauraceae) have been assigned structures 1 and 2, respectively. They are the first examples of aporphine bases in which all but one of the aromatic positions are oxygenated.

■ The Absorption and the Emission Spectra of Some Substituted 3-Phenylcoumarins

C. Y. Chen* and T. E. Gompf

*Research Laboratories, Eastman Kodak Company, Rochester, New York 14650, U.S.A.

Abstract

Additive substituent rules are described which correlate the absorption and the emission maxima, λ_max and E_max, of 3-phenylcoumarins substituted at 7- and 4’-positions. For these compounds, the correlation between transition energies calculated from simple Hückel Molecular Orbital (HMO) treatment and the observed E_max values is better than that for the observed λ_max values.

■ The Introduction of Methoxy Group to the Aromatic Ring of Heteroaromatic Systems; A Model Study for the Introduction of Methoxy Group to the 5-Position of 3,3-Disubstituted Indoline Alkaloids

Takeshi Oishi,* Mineo Fukui, and Yumiko Endo

*The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-0198, Japan

Abstract

Introduction of methoxy group to the 5-position of 3,3-disubstituted indoline derivative was achieved by the substitution of chlorine of the corresponding 5-chloroindoline with methoxy group, substitution being assisted by chromium tricarbonyl complex formation and by the use of “naked” methoxide anion.

■ Diazapolycyclic Compounds. XV. Opening of the Epoxide Rings in Diazaquinone Adducts: A New Condensed 1,4-Oxazepine Derivative

Berta López, Manuel Lora-Tamayo,* and Pilar Navarro

*President of the Centro Nacional de Química Orgánica, C. S. I. C., Juan de la Cierva 3 , E-28006 Madrid, Spain

Abstract

Epoxidation by m-chloroperbenzoic acid of adducts of 5-hydroxy and 5-chlorophthalazin-1.4-dione and 1,2-dimethylencyclohexane, respectively, is reported. Compounds IIa and IIb, 4a,14a-epoxide derivatives, were transformed into the 1,2-diols IIIa and IIIb by treatment with a mixture of aqueous sulfuric acid and acetone in high yields. Reaction of IIa in an alkaline solution resulted in opening of the ring C of pyridazinedione, yielding an intermediate sodium carboxylate IV which, in acidic medium, led to the formation of V, this compound being isolated in another different crystalline form VI. All structures have been determined by analytical and ir, pmr and mass spectroscopic evidences. The structure of V and VI was unambigously established by X-ray analysis.

■ Sulfur Heterocycles from the Reaction of α-Diazo Ketones with Carbon Disulfide

Peter Yates* and J. A. Eenkhorn

*Lash Miller Chemical Laboratories, University of Toronto, Toronto, Ontario, M5S, 1A1, Canada

Abstract

The major determining factor of the course of the reactions of α-diazo ketones RCOCN₂R’ with carbon disulfide is the nature of R’. When R’ = Ph, 1,3-dithiolanes are the sole products; when R’ = Me, both 1,3-dithiolanes and 1,3-dithietanes are formed; when R’ = H, a 1,2,3-thiadiazole is formed.

■ Isolation of an Insect Antifeedant N-Methylflindersine and Several Benz[c]phenanthridine Alkaloids from East African Plants; A Comment on Chelerythrine

Frances Y. Chou, Kurt Hostettmann, Isao Kubo, Koji Nakanishi,* and Makoto Taniguchi

*Department of Chemistry, Columbia University, 3000 Broadway, Mail Code 3114, New York, New York 10027, U.S.A.

Abstract

Several benzphenanthridine type alkaloids have been isolated by following insect antifeedant assays for fractionation. There is a possibility that the well-known chelerythrine could be an artefact, at least in the present case.

■ The Role of Isovincoside (Strictosidine) in the Biosynthesis of the Indole Alkaloids

A. I. Scott,* S. L. Lee, P. de Capite, M. G. Culver, and C. R. Hutchinson

*Department of Chemistry, Texas A & M University, College Station, Texas 77843-3255, U.S.A.