HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Tetsuji Kametani's Special Issues, Vol. 15, No. 2, 1981
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■ Structure and Synthesis of Bissantanolides
Seiichi Inayama,* Tetsushi Ohsaka, Tetsuichi Shibata, Tadaaki Hirose, Takeshi Kawamata, Hitoshi Hori, and Yoichi Iitaka
*Pharmaceutical Institute, Keio University, Shinanomachi 35, Shinjuku, Tokyo 160-0016, Japan
Abstract
2-Hydroxy-hexahydro-l-α-santonins (1) and (2) were transformed in reasonable yield to the corresponding bissantanolides (3) and (4) using p-toluenesulfonic acid, respectively. The structures and conformations of (3) and (4) were determined on the basis of their spectral data and X-ray crystallographic analysis of (3).
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■ A Novel Synthesis of Pyrroles by the Reactions of Tris(alkylthio)cyclopropenium Salt with Amines
Shigeo Yoneda, Hideo Hirai, and Zen-ichi Yoshida*
*Department of Synthetic Chemistry, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan
Abstract
“One pot” synthesis of 2,3-bis(alkylthio)pyrroles in 45~80% yields under mild conditions was achieved by the reactions of tris(tert-butylthio)cyclopropenium salt (1) with secondary amines in the presence of t-BuOK in DMF. Although the reaction of 1 with primary amine such as methylamine gave only the ring opening product, the use of primary amines having structure of XCH2NH2 (X=CN, COOMe, Ph) resulted in the formation of the pyrroles bearing the substituent at the α-position in 44~71% yields.
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■ Studies on 3,5-Dioxopiperidines: Novel and Facil Synthetic Routes to 3-Amino-5-hydroxypyridine Derivatives
Yasumitsu Tamura,* Masanobu Fujita, Ling Ching Chen, Hiroshi Kiyokawa, Kyoji Ueno, and Yasuyuki Kita
*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
Three novel synthetic routes to the title compounds were described. Modified Polonovski reaction of 3-acetamido-1-benzyl-5-oxo-3,4-dehydropiperidine (4) or Semmler-Wolff aromatization of 1-benzyl-3-methoxy-5-oxo-3,4-dehydropiperidine oxime (9) followed by reductive debenzylations gave 3-acetamido-5-hydroxypyridine (6) or 3-acetamido-5-methoxypyridine (11), respectively. Nucleophilic replacement of 3,5-dibromopyridine N-oxide (13) with methoxy and amino groups followed by deoxygenation gave 3-amino-5-methoxypyridine (12) .
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■ A Novel Conversion of Thiochroman-4-ones to Tetrahydro-1-beozothiepin-5-ones via Sulfonium Methylides
Yasumitsu Tamura,* Yasushi Takebe, Chisato Mukai, and Masazumi Ikeda
*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
Thermal reaction of thiochroman-4-ones with dimethyl diazomalonate in the presence of cupric sulfate gave the corresponding biscarbomethoxymethylides (4) and 2,3,4,5-tetrahydro-1-benzothiepin-5-ones (5). Treatment of the sulfonium methylides (4) with triethylamine afforded (5) and/or ring opening products (6).
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■ The Acid-catalyzed Epimerization at the Sulfur Atom of Optically Active 1,2,3-Benzoxathiazine 2-Oxide and Stereospecificity in Its Nucleophilic Substitution
Kunio Hiroi,* Ryuichi Kitayama, and Shuko Sato
*Department of Synthetic Organic Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
The acid-catalyzed epimerization of 2a was accomplished under extremely mild conditions by using hydrogen chloride, BF3 etherate, trifluoroacetic acid, acetic acid, and AlCl3 to give 2b. The action of nucleophiles to 2 proceeded highly stereospecifically with inversion of configuration.
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■ Synthesis of 3-(3-Amino-3-carboxypropyl)uridine (A Modified Nucleoside in Certain RNAS) by Four Component Condensation
Kiyomi Tsuchida,* Yoshihisa Mizuno, and Kazuyoshi Ikeda
*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan
Abstract
3-(3-Amino-3-carboxypropyl)uridine [a modified nucleoside in certain transfer RNA (viz., Echerichia coli tRNA1Ile)] was prepared by a simultaneous condensation of four components [aldehyde, (2-picolyl 1-oxide)amine, cyclohexenyl-isocyanide and acetic acid] as the key reaction.
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■ A New Toxic Fungal Metabolite, Silvaticamide from Aspergillus silvaticus
Mikio Yamazaki,* Haruhiro Fujimoto, Yoichi Ohta, Yoichi Iitaka, and Akiko Itai
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
In this brief report, the isolation and structure of silvaticamide which was isolated from a toxic strain of Aspergillus silvaticus as a toxic principle are described.
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■ N7-Alkylation and Ring-transformation of N6-Acyl-9-substituted Adenines
Yoshifumi Maki,* Mikio Suzuki, Keiji Kameyama, Masaru Kawai, Munehiro Suzuki, and Magoichi Sako
*Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Abstract
An N6-acyl group in 9-substituted adenines shows the prominent substituent effect in the alkylation with alkyl halides; In a sharp contrast to 9-substituted adenines, alkylation of their N6-acyl derivatives occurred at N7-nitrogen rather than N1-nitrogen. The N6-acyl-7-alkyl-9-substituted adeninium halogenides thus prepared were converted into 7-substituted adenine and pteridine derivatives.
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■ On Reaction Rate for Hydrolysis of Substituted Cyclic Nitrosoureas
Yutaka Kawazoe* and Masanari Kato
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
The rates for hydrolyses of 20 derivatives of N-nitrosodimethyleneurea and N-nitrosotrimethyleneurea were measured. Discussion is made on the relationship between structure and rate for hydrolysis.
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■ Formation of Isocyanates by Thermal Reactions of 4-Hydroxy-5,5-dimethyl-4-phenyloxazolidone-2 Derivatives
Norio Saito, Kiyotaka Hatakeda, Shota Ito, Takashi Asano,* and Takashi Toda
*Goverment Industrial Research Institute, Tohoku, Nigatake, Haranomachi, Sendai 983, Japan
Abstract
Thermolysis of 3N-substituted 4-hydroxy-5,5-dimethyl-4-phenyloxazolidone-2 derivatives, which were prepared by the reaction of carbon dioxide and α-bromo-isobutyrophenone in the presence of primary amines, afforded corresponding isocyanates derived from 3N-substituents.
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■ A Novel Synthesis of Dibenzo[c,f ]-1-azabicyclo[3.3.1]nonanes
Hiroshi Hara, Osamu Hoshino, and Bunsuke Umezawa*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
Treatment of the N-benzylated p-quinol acetates (1a and 1b) with trifluoroacetic acid gave (±)-3-hydroxydibenzoazabicyclononanes (5a and 5c) in good yields. On the other hand, lead tetraacetate oxidation of 2-benzyl-6-hydroxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline (3a) the o-quinol acetate (6), which rearranged into the 4-acetoxy-6-hydroxy derivative (4a) at room temperature. Acid treatment of the 4-acetate (4a) afforded a cyclization product (5e) having the same skeleton as that of 5a.
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■ The Synthesis of 8-Aryl-1,2,3,4-tetrahydroisoquinolines
Hiroshi Hara, Osamu Hoshino, and Bunsuke Umezawa*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
Treatment of a mixture of the p-quinol acetate (1a) and aryl alkyl ethers with trifluoroacetic acid gave the 8-aryl-1,2,3,4-tetrahydroisoquinolines (5a-f) in good yields. Similar reaction of 1a and corypalline (2a) afforded the corypalline dimer (7).
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■ Oxidation of Aporphines by Triplet Benzophenone
Luis Castedo,* Teresa Iglesias, Alberto Puga, José M.Saá, and Rafael Suau.
*Department of Organic Chemistry, Laboratory of Medicinal Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15706, Santiago de Compostela, Spain
Abstract
A mild and efficient method to dehydrogenate nonphenolic and phenolic aporphine and noraporphine alkaloids is described. It is based on the photoreduction of benzophenone by amines.
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■ Condensation Products of the Porphyrin Precursor 5-Aminolevulinic Acid
Burchard Franck* and Helmut Stratmann
*Organisch-Chemisches Institut, Universität Münster, Orleansring 23,D-4400 Münster, Germany
Abstract
Condensation of the biogenetic porphyrin precursor 5-aminolevulinic acid (1) in alkaline solution yields besides some porphobilinogen (2) a dihydropyrazine (6) as the predominant product, which was isolated and characterized after dehydrogenation to the stable pyrazine (7a). This ends a longstanding uncertainty and reveals that the azomethine reaction, as can be expected for α-aminoketones, is strongly preferred by 5-aminolevulinic acid (1) under nonenzymatic conditions. A nor-porphobilinogen (9) was formed by condensation of a protected aminoacetoacetic ester with (1).
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■ Structure, Chemistry, and Antimalarial Properties of Mefloquineaziridine
Manfred Rösner, Arnold Brossi,* and James V.Silverton
*Laboratory of Chemistry, Metabolism and Digestive Diseases, National Institute of Arthritis, Bethesda, Marylanf 20014, U.S.A.
Abstract
Mefloquine, a synthetic antimalarial, can be converted into a bicyclic aziridine which has photochromic properties in the solid state. The structure of this aziridine was corroborated by a single crystal X-ray analysis. Reaction of mefloquine-aziridine with acetic anhydride afforded derivatives of mefloquine, with retention of configuration. None of the tested compounds showed antimalarial activity.
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■ Reactions with Indole Derivatives, XLV. The Stereoselextive Total Synthesis of Akagerine
Werner Benson and Ekkehard Winterfeldt*
*Institut fuer Organische Chemie, Universitaet Hannover, Schneiderberg 1B,D-3000 Hannover, Germany
Abstract
A stereoconvergent approach to a pentacyclic dilactame (4) is reported and its conversion into the new indole alkaloid akagerine is described.
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■ A Novel Thermal Rearrangement of 1-Tritylimidazoles
Ikutaro Saji, Katsumi Tamoto, Hiroshi Yamazaki, and Hideo Agui*
*Research Department, Sumitomo Chemical Co. Ltd., 4-2-1, Takatsukasa, Takarazuka, Hyogo, Japan
Abstract
Heating of 1-[(2-chlorophenyl)diphenylmethyl]imidazole (1a) afforded (2-chlorophenyl)-[4-(imidazol-1-yl)phenyl]phenylmethane (2a). Similarly 1-tritylimidazole was converted to diphenyl-[4-(imidazol-1-yl)phenyl]methane (2b).
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■ Lithiation of Some 3[2-(2’-Bromophenyl)ethyl]thiophenes and Intramolecular Transmetalation
Salo Gronowitz,* Karin Stenhammar, and Leif Svensson
*Departamento de Quimica/ Instituto de Tecnologia Quimica, UPV-CSIC, Universidad Politécnica de Valencia, Apartado 22012, E-46071-Valencia, Spain
Abstract
The reaction of some halo-1-(thienyl)-2-phenylethanes such as 3-(2-phenylethyl)thiophene (1), 3-[2-(2’-bromophenyl)ethyl]thiophene (2), 4-[2-(2’-bromo-4’-chlorophenyl)ethyl]-2-methylthiophene (3) and 4-[2-(2’-bromophenyl)ethyl]-2-chlorothiophene (4) with butyllithium and lithium-diisopropylamide (LDA) under various conditions has been investigated. Competition between halogen-metal exchange in the benzene ring and metalation of the thiophene ring was observed and an intramolecular transmetalation reaction was found.
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■ A Convenient Synthesis of β-(1-lmidazolyl)enones from α,β-Dibromoketones
C. Kashima,* M. Shimizu, and T. Tajima
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
As the convenient preparative method of β-(substituted)-phenyl-β-(1-imidazolyl)enones, we succeeded in the preparation of β-aryl-β-(1-imidazolyl)enones from α,β-dibromo-β-arylketones with imidazole in the presence of triethylamine.
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■ Syntheses of Bifunctional Spin Label Molecules and Their Orientations in Membranes
Man Wing Tse-Tang, Betty Jean Gaffney,* and Robert E. Kelly
*The Johns Hopkins, Department of Chemistry, Baltimore, Maryland, U.S.A.
Abstract
The synthesis of new derivatives of substituted pyrrolidine nitroxide free radicals is reported. The molecules are hydrophobic and bifunctional. A preliminary study of their orientation in lipid model membranes has been made by EPR. Molecules having chains of up to 17 atoms and polar end groups take up a conformation in membranes which is tentatively assigned to a bent configuration with both functional groups on one side of the membrane. These molecules are synthetic precursors of spin-labeled cross-linking reagents for membrane proteins.
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■ New Methods and Reagents in Organic Synthesis. 11. Reaction of Trimethylsilyldiazomethane with Aromatic Aldehydes
Norio Hashimoto, Toyohiko Aoyama, and Takayuki Shioiri*
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
Trimethylsilyldiazomethane adds to aromatic aldehydes in the presence of triethylamine in methanolic solution to give epoxides and homologous compounds.
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■ New Methods and Reagents in Organic Synthesis. 12. Reaction of Diethyl Phosphorocyanidate(DEPC) with Aromatic Amine Oxides. A Modified Reissert-Henze Reaction
Shinya Harusawa, Yasumasa Hamada, and Takayuki Shioiri*
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
Diethyl phosphorocyanidate (DEPC) reacts with aromatic amine oxides in the presence of triethylamine to give α-cyanated compounds; the reaction may be called a modified Reissert-Henze reaction.
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■ Photooxygenation of 7-Substituted Cycloheptatrienes
Toyonobu Asao,* Morio Yagihara, and (the late) Yoshio Kitahara
*Department of Chemistry, College of General Education, Tohoku University
Abstract
Photooxygenation of 7-substituted cycloheptatrienes, including the Me, Et, iPr, Ph, CN, COOMe, COOEt, and CONH2 groups was studied, and several products among the tropilidene-type (1 and 2) and norcaradiene-type (3 and 4) endoperoxides, o-substituted benzaldehydes (5), diepoxides (6 and 7), and ketoalcohols (8) were obtained. Mechanism of the formations of the products was discussed. Thermal isomerization of the endoperoxides (1, 3 and 4) to the corresponding diepoxides (10, 6 and 7), and the reaction of the endoperoxides (1 and 3) with triethylamine were examined.
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■ The Structure of Carbazomycin B
Miyuki Kaneda, Katsu-ichi Sakano, Shoshiro Nakamura,* Yoshihiko Kushi, and Yoichi Iitaka
*Institute of Pharamceutical Sciences, Faculty of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
Abstract
The structure of carbazomycin B was determined to be 4-hydroxy-3-methoxy-1,2-dimethylcarbazole by 1H- and 13c-nmr studies of carbazomycin B and its derivatives, and was unequivocally confirmed by X-ray crystallographic analysis.
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■ Chemical Studies on Tuberactinomycin. XVIII. Syntheses of DL-Dihydroviomycidine and DL-Viomycidine
Tateaki Wakamiya,* Kunikazu Konishi, Haruyuki Chaki, Tadashi Teshima, and Tetsuo Shiba
*Department of Chemistry, Faculty of Science, Osaka University, Toyonaka, Osaka 560-8531, Japan
Abstract
Dihydroviomycidine (2) and viomycidine (3) were guanidino amino acids derived artificially from tuberactidine (1) in peptide antibiotics tuberactinomycin A and B (viomycin). The amino acids 2 and 3 of DL-forms were synthesized from common precursor, threo-2-amino-3,5-dihydroxypentanoic acid derivative. Guanidination of 3-hydroxyl group gave 2, while further oxidation of 5-hydroxyl group afforded 3. Both diflavianates of synthetic DL-2 and DL-3 were completely identical with those of the corresponding natural L-compounds in respect of tlc, pc, hplc, amino acid analysis, and nmr.
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■ The 13C-NMR Assignment of Some Spirocyclopropane-attached Derivatives of the Dicyclopentadiene by the Epoxidation Shift
Tosihide Hatsui and Hitoshi Takeshita*
*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan
Abstract
The 13C-NMR assignment of dispiro[cyclopropane-1,3’-tricyclo[5.2.1.02,6]-deca-4’,8’-diene-10’,1”-cyclopropane] and its derivatives was given by the comparison of the magnitudes of the residual coupling in the off-resonance spectra and by the chemical shift differences induced by the epoxidation of a double bonds. This was in accord with the former assignment for the dicyclopentadiene by Nakagawa et al.
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■ Formation of Furo[3,2-c]quinoline Derivatives through the Fries-type Acid-catalyzed Rearrangement of 1-Arylazetidin-2-ones
Shinzo Kano,* Shiroshi Shibuya, and Tsutomu Ebata
*Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan
Abstract
1-Aryl-3-(2-hydroxyalkylidene)azetidin-2-ones were heated with trifluoroacetic acid under reflux for 1.5 hr to give furo[3,2-c]quinoline derivatives in one-step through 2,3-dihydro-3-β-ketoalkyl-4(1H)-quinolone intermediates. By this method, 7,8,9,10-tetrahydro-2-methoxybenzofuro[3,2-c]quinoline (11), 2-methyl-3-phenylfuro[3,2-c]quinoline (15), 2-methylfuro[3,2-c]quinoline (20a), 2-ethyIfuro[3,2-c]quinoline (20b) and 2-methyl-8-methoxyfuro[3,2-c]quinoline (20c) were obtained from the corresponding 1-aryl-3-(2-hydroxyalkylidene)azetidin-2-ones.
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■ Antimicrobial Agents from Higher Plants. New Synthesis and Bioactivity of Tryptanthrin(Indolo-[2,1-b]quinazolin-6,12-dione) and Its Analogues
Lester A. Mitscher,* Wai-Cheong Wong, Teresa DeMeulenaere, Jerzy Sulko, and Stephen Drake
*Department of Medicinal Chemistry, Kansas University, Lawrence, Kansas 66045, U.S.A.
Abstract
Base-catalyzed condensation of substituted isatins and substituted isatoic anhydrides provides a convenient, one-step flexible synthesis of indolo-[2,1-b]-quinazolin-6,12-diones, including the antifungal natural product tryptanthrin. This new process provides the basis for a systematic exploration of the relationship between structure and antimicrobial activity. Preliminary findings demonstrate that non-symmetrically substituted analogues are easily prepared and the method tolerates the presence of a variety of ring substituents.
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■ The Structure of the Enantioselectivity Determining Intermediate in the Phosphine-Rhodium Assisted Asymmetric Hydrogenation of β-Methylene Acids
K. Achiwa*
*Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan
Abstract
The general mechanism of the phosphine-rhodium catalyzed asymmetric hydrogenation of β-methylene acid was proposed to account the chemical evidences on the structure of the enantioselectivity determining key intermediate, [Rh(BPPM)-(β-Methylene Acid)(H2)]+X- (3a).
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■ An Electron Spin Resonance Study on the Properties of 1-Methyl-2-methoxycarbonylpyridinyl and the Dimer
Yusaku Ikegami,* Masako Sawayanagi, and Shozo Kubota
*Institute of Chemical Reaction Science, Tohoku University, Katahira, Aoba-ku, Sendai 980-8577, Japan
Abstract
The electron spin resonance study of the 1-methyl-2-methoxycarbonylpyridinyl radical, which is in equilibrium with a large amount of the dimer in solution, elucidated the hyperfine splitting constants, the remarkable dependence of the signal intensity on temperature, and the line-broadening with a rise in temperature above 0°C. The activation energy for the monomerdimer interconversion was evaluated to be 9.4 kcal/mol in 2-methyltetrahydrofuran. Light irradiation of the dimer in 2-methyltetrahydrofuran at 77 K led to an appearance of the triplet spectrum with D = 0.0155 cm-1 due to the radical pair generated by photochemical dissociation of the dimer. Further irradiation of the solution altered gradually the line shape.