摘要:

J. CHEM. RESEARCH (S), 1997 69 J. Chem. Research (S), 1997, 69 J. Chem. Research (M), 1997, 0556–0567 Synthesis of a Sulfur-bridged Calixarene Burkhard K�onig,*a Martin R�odel,a Ina Dixb and Peter G. Jonesb aInstitut f�ur Organische Chemie der Technischen Universit�at Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany bInstitut f�ur Analytische und Anorganische Chemie der Technischen Universit�at Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany A thiacalix[4]arene was obtained by the reaction of the 2,5-thiophene dianion with SCl2; the analogous reactions of dianions of diaryl thioethers did not yield macrocyclic structures and under the applied conditions diaryl sulfones were further deprotonated and the structure of the fourfold Me3Si-adduct 11 determined by X-ray crystallography.The first thiacalix[4]arene 8 was isolated in small amounts from the reaction of the 2,5-thiophene dianion with SCl2. Thiophene was deprotonated to the 2,5-dianion by treatment with BuLi–TMEDA.6 Slow addition of the biselectrophile SCl2 to a cold solution of the thiophene dianion gave, after work-up, a white solid.From the crude product a small amount of the thiacalix[4]arene 8 could be isolated. The thiophene moieties of the compound rotate freely on the NMR timescale in solution, as shown by simple NMR spectra. To increase the yield of the thiacalix[4]arene 8 a stepwise synthesis was investigated. However, the reaction was improved neither by the use of the thioether 96 nor the sulfone 10.5 In the latter case the regioselectivity of the deprotonation was lost, as illustrated by the formation of the tetrasilylated compound 11 upon treatment of the anion solution with Me3SiCl.The structure of 11 was confirmed by X-ray analysis.7 The thiophene units show an anti arrangement in the solid state and the geometry of the central sulfur atom is nearly ideal tetrahedral. Crystal Data.·C20H38O2S3Si4, monoclinic, a=1663.0(2), b=1055.0(0), c=1736.8(1) pm, b=103.89(1)°, V=2.958(2) nm3, space group P21/n, Z=4. The structure was solved by direct methods and refined anisotropically on F2, using the program SHELXL-93.7 Hydrogen atoms were included as rigid methyl groups or with a riding model.Final refinement with 274 parameters led to a final wR(F2) for all reflections of 0.084, S=0.934, with a conventional R(F) of 0.034; max. Dr 393 e nmµ3. A colourless prism ca. 0.64Å0.44Å0.42 mm was mounted on a glass fibre in inert oil.Measurements were performed on a Siemens P4 diffractometer with an LT-2 lowtemperature attachment at 173 K using graphite-monochromated Mo-Ka radiation (l=71.073 Å). 5196 independent reflections below 2y=50° were measured with the w-scan method. 3794 reflections with F0a4s(F0) were used in the structure solution and refinement.† We conclude that the reaction of dianions with SCl2 is less suitable for the synthesis of heteroatom-bridged macrocycles.Compared to Me2SiCl2,1 the reaction is less selective because of the high reactivity of the biselectrophile SCl2, yielding only small amounts of macrocycles. However, from the reaction of the 2,5-thiophene dianion and SCl2 the first thiacalix[4]arene 8 was isolated. Techniques used: 1H NMR, 13C NMR, MS, UV, IR, combustion analysis, X-ray diffraction References: 7 Schemes: 4 Table 1: Crystal data and structure refinement for 11 Table 2: Atomic coordinates and equivalent isotropic displacement parameters for 11 Table 3: Intramolecular bond distances and angles for 11 Appendix: 1H and 13C NMR spectra for compound 8 Received, 31st October 1996; Accepted, 19th November 1996 Paper E/6/07416B References cited in this synopsis 1 B.K�onig, M. R�odel, P. Bubenitschek and P. G. Jones, Angew. Chem., 1995, 107, 752; Angew. Chem., Int. Ed. Engl., 1995, 34, 661; B. K�onig, M. R�odel, P. Bubenitschek, P. G. Jones and I. Thondorf, J. Org. Chem., 1995, 60, 7406. 5 E. Jones and I. M. Moodie, Tetrahedron, 1965, 21, 2413. 6 L. Brandsma, Preparative Polar Organometallic Chemistry 1, Springer, Berlin, 1990; B. J. Wakefield, Organolithium Methods, Academic Press, London, 1988. 7 G. M. Sheldrick, SHELX-93, Program for Crystal Structure Refinement, University of G�ottingen, G�ottingen, Germany, 1993. *To receive any correspondence. †Atomic coordinates, bond lengths and angles, and thermal parameters are given in the full text and have also been deposited at the Cambridge Crystallographic Data Centre (CCDC). Any request to the CCDC for this material should quote the full literature citation and the reference number 423/3. Scheme 3 Scheme 4 Fig. 1

ISSN:0308-2342    

DOI:10.1039/a607416b

出版商:RSC    

年代:1997

数据来源: RSC

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J. Chem. Research (S), 1997, 70–71 J. Chem. Research (M), 1997, 0501–0508 Attempted Synthesis of Cyclopenta-1,2-diene and Wurtz-like Condensation Products in the Reaction of 2,3-Dibromocycloalkenes with Zinc Mustafa Ceylan,*a Hasan Se6cenb and Ya6sar S�utbeyazb aDepartment of Chemistry, Faculty of Science, Gaziosmanpa6sa University, 60110 Tokat, Turkey bDepartment of Chemistry, Faculty of Science, Atat�urk University, 25240 Erzurum, Turkey Fluoride ion-promoted elimination of 2-bromo-3-trimethylsilylcyclopentene 5 and the reaction of five-, six- and sevenmembered 2,3-dibromocycloalkenes with zinc gave Wurtz-like dimeric products instead of the expected cyclic allenes.Allenes are an important class of unsaturated hydrocarbons which contain two cumulative orthogonal double bonds. In cyclic allenes, ring constraints bend and twist the normally linear, perpendicular allene and result in substantial strain and kinetic reactivity.1 Recently, we reported the synthesis of an allene unit in six- and seven-membered rings by fluoride ion-promoted elimination of a b-halogenosilane.4 In this paper, we applied fluoride ion-promoted elimination of halogenosilane to 5 and zinc catalysed elimination to 4 to synthesise the highly strained cyclic allene cyclopenta-1,2-diene 8.In addition, we applied zinc catalysed elimination to 12 and 13. To synthesise 5, cyclopent-2-enone 1 as starting material was used. Addition of bromine and triethylamine to 1 followed by reduction of 2 with NaBH4 afforded the bromoalcohol 3.Substitution of 3 with PBr3 gave dibromoalkene 4. To convert 4 to 5, a published procedure was used.4 In this reaction, 6 and 7 were also obtained in a combined yield of 13%. When the same reaction was carried out at µ70 °C, the yield of 6 and 7 increased to 55% (Scheme 1). Treatment of 5 with tetrabutylammonium fluoride (Bu4NF) and KF under different conditions resulted in the formation of two isomeric Wurtz-like condensation products 6 and 7 in a combined yield of 48–50% (Scheme 2).Treatment of 4 with activated zinc in DMSO at 85 °C gave 6 and 7 in a combined yield of 58% (Scheme 3). The structures of 6 and 7 were determined on the basis of 1H and 13C NMR spectral data. The identical product distribution from the three different reactions, implies a common intermediate 11. 12 and 13 were synthesised according to literature procedures.4,6 Treatment of 12 and 13 with activated zinc in THF at 65 °C resulted in the formation of two isomeric Wurtz-like condensation products 18,19 (combined yield, 73%) and 20,21 (combined yield, 68%), respectively.The same condensation products 18, 19, 20, 21 were also obtained in the synthesis of silyl compounds 167 and 174 from 70 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence. Scheme 1 Scheme 2 Reagents and conditions: i, Bu4NF, DMSO, 85 °C; ii, Bu4NF, toluene, 110 °C; iii, KF, AgNO3, HMPA, 110 °C; iv, Bu4NF, THF, DBI, 65 °C; v, Bu4NF, toluene, DBI, 110 °Cdibromides 12 and 13 and the mesylate compound 22 which was synthesised by a literature procedure.3a,8 Treatment of 12 and 13 with trimethylsilylcopper (CuSiMe3) gave the silyl compounds 16 (54%) and 17 (20%) and the condensation products 18,19 (combined yield, 10%) and 20,21 (combined yield, 28%), respectively.In addition, treatment of 22 with trimethylsilylcopper at µ40 °C also gave 17 (6%) and 20,21 (combined yield, 35%).In contrast, reaction of 16 and 17 with Bu4NF had resulted in the formation of 14 and 15 in good yield4 (Scheme 5). We are indebted to the Atat�urk University for financial support of this work (Project No: 1991/4) and the State Planning Organization of Turkey (DPT) for purchasing a 200 MHz NMR. Techniques used: 1H and 13C NMR, IR spectrometry References: 8 Schemes: 5 Received, 8th August 1996; Accepted, 11th November 1996 Paper E/6/05543E References cited in this synopsis 1 R. P. Johnson, Chem. Rev., 1989, 89, 1111; H. F. Schuster and G. M. Coppola, Allenes in Organic Synthesis, Wiley, New York, 1984. 3 (a) M. Balci and W. M. Jones, J. Am. Chem. Soc., 1980, 102, 7607. 4 Y. S�utbeyaz, M. Ceylan and H. Seçen, J. Chem. Res., 1993, (S) 293; (M) 2189. 6 J. Sonnenberg and S. Winstein, J. Org. Chem., 1962, 27, 748. 7 S. E. Denmark and C. Klix, Tetrahedron, 1988, 44, 4043. 8 Leo A. Paquette and A. Leone-Bay, J. Am. Chem. Soc., 1983, 105, 7352. J. CHEM. RESEARCH (S), 1997 71 Scheme 3

ISSN:0308-2342    

DOI:10.1039/a605543e

出版商:RSC    

年代:1997

数据来源: RSC

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OH HO R R R R HO HO HO OH OH OH OOC COO H3C CH3 CH3 H3C COO COO COO OOC OOC OOC O O O O O O O O CO CO CO CO CO CO CO CO O O O O O O O O CO CO CO CO CO CO CO CO a R = Me b R = Ph c R = C6H4OH- p e 1 2 c b d 2 O CO f 5 O CO 6 4 O CO 1 3 O CO 4 3 H H H H a J. Chem. Research (S), 1997, 72–73 J. Chem. Research (M), 1997, 0509–0517 Synthesis and Solvent Inclusion Complexation Studies of Benzoyl Derivatives of Resorcinol-aldehyde Tetramers by 1H NMR and Thermogravimetric Analysis Harmit Singh* and Serjinder Singh Department of Food Science and Technology, Guru Nanak Dev University, Amritsar 143005, India Benzoyl derivatives of resorcinol-aldehyde cyclophanes have been synthesized in order to observe their binding behaviour towards inclusion complex formation with solvent molecules using thermogravimeteric and 1H NMR techniques.Tetrameric cyclophanes 1a–c, obtained from the cyclization of resorcinol and acetaldehyde, benzaldehyde and p-hydroxybenzaldehyde respectively, have been used to synthesize 2–4 by the Schotten–Baumann reaction.The increased number of phenyl moieties is supposed to increase the size of the hydrophobic cavity of 1a–c. The inclusion properties of 2 and 3 have been studied by 1H NMR and thermogravimeteric analysis in order to understand the hydrophobic effect of the additional phenyl group. The results confirm that the size of the cavity is smaller in 3 than in 2. Compound 3 does not form any inclusion complex with molecules containing bigger atoms, e.g.CHCl3, and is therefore more selective, whereas 2 is more versatile. 1H NMR spectroscopy showed maximum binding for smaller molecules like CH3CN and CHCl3 with host 2. Complexation appears to involve the benzoyl groups, as indicated by the complexation-induced shift in the 1H NMR signals of the host protons (Table 4). The substituted cyclophanes 2–4 were characterized by elemental analysis and NMR spectroscopy. The resorcinol protons of the tetramer 1a were overlapped by the benzoyl protons in 2–3 and 4 and integration favoured the formation of octabenzoates.There were no D2O-exchangeable protons, indicating the absence of any free resorcinol OH. The 13C NMR spectrum of 2 contained a quartet for C-1 at d 19.8 which was replaced by a singlet in 3 and 4. The carbonyl C-7 was at d 164.39 while C-3, C-4 and C-5 gave signals at d 130.2 (s), 151.67 (s) (due to attached O) and 116.89 (d) respectively. The C-2 doublet was present at d 44.94 (s) in 2 and 30.3 (s) in 3.C-3, C-6, C-8, C-9, C-10 and C-11 were very close to each other as overlapping signals at d 130.2 (s), 129.44 (d), 136.2 (s), 128.2 (d), 128.35 (d) and 131.6. As investigated by 1H NMR1,2 and X-ray crystallographic 72 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence.studies,3 the host 1a forms inclusion complexes with small guests like the methyl group of quaternary amines, CHCl3 and CH3CN, as these fitted best in the cavity.It was thought that the cavity size should increase with the presence of benzoyl phenyls around the central bowl of the cyclophane 1. As is clear from the present study the effective size of the cavity remains almost the same, although the benzoyl groups help in binding the guest, as supported by 1H NMR studies. Experiments were designed to check directly the loss of guest thermogravimetrically. The sample was weighed on a microbalance after recrystallization and drying at 25 °C by vacuum suction from the solvent guest.The same sample was also weighed after drying at 100 °C by vacuum suction. The difference in the weight gave the ratio of host to guest (Tables 1–3). Host 2 was found to accommodate small apolar molecules such as CH2Cl2, CHCl3, C6H6 and ethyl acetate, forming 1:1 host–guest complexes, while with acetone and methanol 2 formed 1: 2 complexes (Table 1). Host 3 forms a high complex ratio with methanol, i.e., 1: 4 (Table 2), and it was interesting that 3 did not form any inclusion complex with CHCl3 because of the three large chlorine atoms, con- firming the previously established fact4 that 1b is smaller than 1a (from which 3 and 2 were synthesized).To explore the effect of size in more detail, the more selective 3 was investigated further with regard to its binding with various alcohols (Table 3). It was clear from these studies that linear molecules were preferred over branched ones.tert-Butyl alcohol did not form any complex with 3 whereas n-butanol formed a 1:1 complex. 1H NMR Complexation-induced Shifts of Solvent Guest Protons with Host 2.·It was interesting to study the less selective host 2 for its size discrimination by 1H NMR investigations. Compound 2, with a large hydrophobic cavity encircled by twelve phenyl groups, was recrystallized from various solvents. The host–guest inclusion complexation was studied by the shifts in the host as well as the guest signals. The shift in signals indicates clearly the interaction of various guests with different sites of 2.The Ha protons of host 2 were shifted upfield by d 0.274–0.165 for various solvents, but the effect on Hb was negligible (except for benzene), signifying that the effect on Ha is due to strain in the cyclophane ring while binding the guest. The protons of the resorcinol units, i.e. Hc and Hd, are deeply buried under the benzoyl groups and did not interact with the guest, as indicated by negligible shifts in the signals for these protons (Table 4).The maximum shift of the benzoyl signals was from d µ0.463 to µ0.297 for the He and d 0.456 for the Hf protons. The He protons showed a downfield shift implying a decrease in electron density at the ortho position of the benzoyl groups in the inclusion complexes. That the Hf protons showed the maximum upfield shift of all the host 2 protons indicated quite clearly that the benzoyl groups are enclosing the guest.The trend of the complexation-induced shifts also shows that the basic cavity, lined by four resorcinol units in 1a, is supplemented for its binding behaviour in 2 by the addition of eight benzoyl units which act as a source of lipophilic interactions. The signal shifts for the guest also indicate clearly the role of the benzoyl groups in 2 in binding the guest. The CH3OH groups show only a negligible shift (Table 4), indicating that in solution the cavity may be too hydrophobic after addition of the eight phenyls to attract hydrophilic molecules such as methanol.Shifts are maximal for apolar guests such as CHCl3, CH3CN and C6H6 (d 0.19, 0.29 and 0.17 respectively) (Table 4). Financial aid from CSIR and DST (New Delhi) is greatly acknowledged. Techniques used: 1H NMR, 13C NMR, microanalysis, thermogravimetry References: 15 Tables: 4 Received, 27th March 1996; Accepted, 13th November 1996 Paper E/6/02153K References cited in this synopsis 1 H.Schnieder, D. Guttes and U. Schnieder, Angew. Chem., Int. Ed. Engl., 1986, 25, 647. 2 J. R. Moran, S. Kharbach and D. J. Cram, J. Am. Chem. Soc., 1982, 104, 5828. 3 T. M. Linda, J. A. Tucker, E. D. Jurgen, W. I. A. Breyent, J. C. Shermon, R. C. Helgeson, C. B. Knobler and D. J. Cram, J. Org. Chem., 1989, 54, 1305. 4 S. Singh and H. Singh, Indian J. Chem., 1990, 29B, 601. J. CHEM. RESEARCH (S), 1997 73 Table 1 Inclusion complexes of 2 with various solvent guests Loss calculated Loss Host:guest Solvent for 1:1 observed ratio in guest complex (mg) (mg) complex CH2Cl2 CHCl2 C6H6 AcoEt Me2CO MeOH 1,4-Dioxane THF 0.28 0.18 0.22 0.16 0.29 0.05 0.30 0.32 0.30 0.18 0.23 0.14 0.58 0.09 0.97 0.53 1:1 1:1 1:1 1:1 1:2 1:2 1:2 2:3 Table 2 Inclusion complexes of 3 with various solvent guests Loss calculated Loss Host:guest Solvent for 1:1 observed ratio in guest complex (mg) (mg) complex CH2Cl2 CHCl3 C6H6 AcOEt Me2CO MeOH THF 0.08 0.20 0.05 0.25 0.14 0.04 0.20 0.04 0.06 0.14 0.23 0.08 0.17 0.19 2:1 1:0 1:3 1:1 2:1 1:4 1:1 Table 3 Inclusion complexes of 3 with various alcohols Loss calculated Loss Host:guest for 1:1 observed ratio in Alcohol complex (mg) (mg) complex MeOH PriOH BuiOH BunOH EtOH 0.04 0.17 0.15 0.15 0.1 0.17 0.24 0.17 0 0.09 1:4 2:3 1:0 1:1 1:1 Table 4 1H NMR complexation-induced shifts of host 2 and guest solventsa Dd (shift for host protons) MeOH CHCl3 MeCN C6H6 EtOH Et2O Ha Hb Hc Hd He Hf Shift of guest signal 0.27 0.02 0.09 0.06 µ0.29 0.54 0.02 0.20 0.03 0.09 0.05 µ0.36 0.48 0.19 0.26 0.03 0.06 0.00 µ0.29 0.51 0.29 0.24 0.17 0.06 0.06 µ0.29 0.61 0.17 0.16 µ0.02 0.03 0.03 µ0.39 0.45 0.09b 0.20 0.03 0.03 0.05 µ0.46 0.048 0.07b aNegative indicates a downfield shift.bShift for CH3.

ISSN:0308-2342    

DOI:10.1039/a602153k

出版商:RSC    

年代:1997

数据来源: RSC

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O CH2 O CH2 ROCH2 OH [CH2]2 CH2OR OH 2a [CH2] n 3a n = 2 ROH 4a R = Me 5a R = Et 6a R = Ac HO OH O O OH MeO OMe OH Ag2O C6H6 2a (70%) 4a (76%) 1a Ag2O MeOH J. Chem. Research (S), 1997, 74–75 J. Chem. Research (M), 1997, 0518–0529 Medium-sized Cyclophanes. Part 40.1 Generation of a Bis(o-quinone methide) from [n.2]Cyclophanes having a Spiro Skeleton and their Trapping Reaction with Nucleophiles and Dienophiles Takehiko Yamato,*a Jun-ichi Matsumoto,a Mitsuhiro Sato,a Koji Fujitaa and Yoshiaki Naganob aDepartment of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga-shi, Saga 840, Japan bTohwa Institute of Science, Tohwa University, 1-1 Chikushigaoka, Minami-ku, Fukuoka 815, Japan Spiro compounds 2, obtained from the oxidation of dihydroxy[n.2]metacyclophanes 1 with K3Fe(CN)6, readily generate a bis(o-quinone methide) 3 with mild heating which is trapped with nucleophiles and dienophiles to give diarylalkanes 4–6 and [4+2] cycloadducts 8, respectively.Quinone methides have been postulated as reactive intermediates in organic reactions for many years.2 A quinone methide with an unsubstituted methylene group has not been isolated except at low temperatures3 or in the case of highly hindered molecules.4 Filar and Winstein5 have shown the existence of a p-quinone methide in dilute solution. A quinone methide intermediate is usually identified from product studies. Balon6 has reported the oxidation of 4-substituted 2,6-dimethylphenols with various oxidizing agents such as silver oxide in methanol to form 4-substituted 2-methoxymethyl-6-methylphenols by trapping the o-quinone methide with the nucleophilic methanol.o-Quinone methide intermediate formation was subsequently confirmed by the formation of a [4+2] cycloadduct with reactive dienophiles to form chromane skeletons.7 We recently found that the oxidation of 5,13-di-tert-butyl- 8,16-dihydroxy[2.2]MCP (MCP=metacyclophane) 1a with K3Fe(CN)6 afforded the intramolecular O–C coupling product 2a having a spiro skeleton.8–11 Compound 2a corresponds to the intramolecular [4+2] cycloadduct of the bis(oquinone methide) 3a.Here we report the cycloreversion of 2 with mild heating to generate 3 and the reaction of 2 with alcohols, acetic acid and ethenes. The effects on strain with increasing methylene bridge length of the cycloreversion product are also investigated. Oxidation of 5,13-di-tert-butyl-8,16-dihydroxy[2.2]MCP 1a12 in refluxing benzene by Ag2O, as well as by aqueous K3Fe(CN)6, for 3 h afforded the intramolecular O–C coupling product 2a in 70% yield (Scheme 1).When methanol was used instead of benzene, an unexpected product 4a, which corresponds to a 1: 2-adduct of 3a and methanol, was obtained in 76% yield. The formation of 4a suggests that the spiro compound 2a produced in the oxidation of 1a by Ag2O reacted with methanol. Therefore, 2a was treated separately with methanol, ethanol and acetic acid.When 2a was treated with boiling methanol, the expected 4a, whose structure was determined by its spectral data, was obtained in 76% yield. Ethanol similarly reacted with 2a to give 5a in good yield. Compound 2a reacted with acetic acid to give diester 6a in good yield. 74 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence (e-mail: yamatot@cc.saga-u. ac.jp). Scheme 1 Scheme 2 Table 1 Reaction of 2a with methanol, ethanol and acetic acid Reagent T/°C t/h Products (%)a MeOH EtOH HOAc reflux reflux 100–105 322 4a (76) 5a (96) 6a (84) aIsolated yields.O O R2 R1 R1 R2 R1 R2 benzene reflux, 24 h 2a [3a] a R1 = H, R2 = OEt b R1 = Me, R2 = Ph (96%) (99%) 8 OH EtOCH2 [CH2] n OH CH2OEt EtOH reflux 2 [3] a n = 2 b n = 3 c n = 4 d n = 5 5 The above results suggest the intermediate formation of the bis(o-quinone methide) 3a from the spiro metacyclophane 2a.In order to confirm this, reactions of 2a with electron- rich dienophiles3 such as ethyl vinyl ether (7a) and a-methylstyrene in refluxing benzene (7b) were investigated. The expected [4+2] cycloadducts, 8a and 8b, were obtained in 96 and 99% yield, respectively.The reaction of 2a with electron-deficient dimethyl acetylenedicarboxylate did not give the expected cycloadduct; instead a complex mixture of unidentified products was obtained. In conclusion, the spiro compound 2a is a convenient precursor of the bis(o-quinone methide) 3a, generated after mild heating of 2a.These novel ring fissions, generating bis(o-quinone methide) intermediate 3a after mild heating of 2a, might occur as a result of releasing the strain in the spiro compound 2a. Thus, there is substantial interest in investigating the effects on strain of increasing the length of the methylene bridge of spiro [n.2]cyclophanes by the formation of bis(oquinone methide) intermediates. W h e n 5 p, 6 - d i - t e r t - b u t y l - 3 p, 8 - p r o p a n o s p i r o [ c h r o m a n e - 2,1p-cyclohexa-3p,5p-dien]-2p-one 2b was treated with boiling ethanol for 2 h, the expected product 5b derived from a bis(oquinone methide) intermediate was obtained in 13% yield along with 87% recovery of the starting compound.Prolonged reaction times led to complete formation of 5b. Similar treatment of the larger-ring-sized spiro compound 2c (n=4) with boiling ethanol afforded only 5c in 16% yield, while with the larger-ring spiro compound 2d only recovered starting material was obtained.Although Biali et al.14 reported the preparation of bis- (spirodienone) derivatives of p-tert-butylcalix[4]arene and various reactions in protic media, the present novel ring fission to generate bis(o-quinone methide) intermediates has not been observed so far. Therefore, the above results suggest that the effects of strain in [n.2]cyclophanes having a spiro skeleton 2 do exist. Thus, the generation of a bis(oquinone methide) on mild heating is possible for [2.2]cyclophane 2a and [3.2]cyclophane 2b having a spiro skeleton and can be attributed to the strain of a medium ring which can be released by conversion into the strain-free bis(o-quinone methides) 3a and 3b.We conclude that the spiro compounds 2 obtained in the oxidation of dihydroxy[n.2]MCPs 1 with K3Fe(CN)6, readily generate a bis(o-quinone methide) 3 on mild heating, which is trapped with methanol, ethanol and acetic acid to give diarylalkanes.Techniques used: 1H NMR, IR, MS, VPC References: 14 Tables: 2 Schemes: 5 Received, 13th August 1996; Accepted, 18th November 1996 Paper E/6/05667I References cited in this synopsis 1 Part 39: T. Yamato, K. Fujita, T. Ando, S. Ide, Y. Nagano and M. Tashiro, J. Chem. Res., 1996, (S) 264; (M) 1434. 2 A. B. Turner, Quart. Rev., 1964, 28, 347. 3 (b) A. Merrijan, B. A. Shoulders and P. D. Gardner, J. Org. Chem., 1963, 28, 2148. 4 A. Bistrzycki and C. Herbst, Chem. Ber., 1903, 36, 2335. 5 L. J. Filar and S. Winstein, Tetrahedron Lett., 1960, 25, 9. 6 D. A. Balon, J. Org. Chem., 1970, 35, 715. 7 D. A. Balon, J. Org. Chem., 1970, 35, 3666. 8 M. Tashiro, T. Yamato, S. Horie and S. Mataka, Chem. Pharm. Bull., 1984, 32, 1641. 9 T. Yamato, J. Matsumoto, K. Tokuhisa, K. Suehiro, S. Horie and M. Tashiro, J. Org. Chem., 1992, 57, 6368. 10 T. Yamato, J. Matsumoto, K. Tokuhisa, K. Suehiro and M. Tashiro, J. Chem. Soc., Chem. Commun., 1992, 865. 11 T. Yamato, K. Fujita, J. Matsumoto, M. Sato, Y. Nagano and M. Tashiro, J. Chem. Res. (S), 1996, 262. 12 (b) M. Tashiro, K. Koya and T. Yamato, J. Am. Chem. Soc., 1982, 104, 3707. 14 A. M. Litwak, F. Grynszpan, O. Aleksiuk, S. Cohen and S. E. Biali, J. Org. Chem., 1993, 58, 393. J. CHEM. RESEARCH (S), 1997 75 Scheme 3 Scheme 5 Table 2 Reaction of 2 with EtOH Substrate 2 t/h Products 5 (%)a Recovd. a bbc d 22 36 36 36 (100) (13) (100) (16) (0) (0) (87) (0) (84) (100) aYields were determined from 1H NMR spectroscopy.

ISSN:0308-2342    

DOI:10.1039/a605667i

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N F F F F R N C6F5CH R N F F HN F R R N F F X F Me Me N F a R = H b R = OMe c R = Me d R = But e R = F f R = Cl g R = Br a R = H b R = OMe c R = Me d R = But e R = F f R = Cl g R = Br 4 1 a R = H b R = OMe c R = Me d R = But e R = F f R = Cl g R = Br 7 a X = F b X = 3, 5-Me2C6H3NH 11 12 OMe J. Chem. Research (S), 1997, 76–77 J. Chem. Research (M), 1997, 0530–0555 One-pot Synthesis of 1,2,3,4-Tetrafluoroacridines from Pentafluorobenzaldehyde1 Adrian J. Adamson, R. Eric Banks,* Roy Fields and Anthony E.Tipping* Chemistry Department, University of Manchester Institute of Science and Technology (UMIST), Manchester M60 1QD, UK 1,2,3,4-Tetrafluoroacridines (accompanied in certain cases by their 3-arylamino derivatives) have been prepared in onepot fashion (via formation in situ of the corresponding Schiff bases) by heating pentafluorobenzaldehyde with a 2 molar equivalence of aniline, para-substituted anilines 4-RC6H4NH2 (R=OMe, Me, But, F, Cl, Br) or 3,5-dimethylaniline in boiling o-dichlorobenzene.It seems that 1,2,3,4-tetrafluoroacridine (1a) was first synthesised in the early 1960s from bromobenzene via a low-yield, laborious, multi-step synthesis based on a modified Lehmstedt –Tanasescu rearrangement.2 Since this route involved both 1,2,3,4-tetrafluoro-9(10H)-acridone and 9-chloro- 1,2,3,4-tetrafluoroacridine as intermediates, it possessed potential as a source of several other derivatives of 1,2,3,4-tetrafluoroacridine; however, this opportunity seems not to have been pursued, although the development of other routes to 1,2,3,4-tetrafluoro-9(10H)-acridone (electrochemical oxidation of 2-amino-3,4,5,6-tetrafluorobenzophenone; KF-driven cyclization of 2p-amino-2,3,4,5,6-pentafluorobenzophenone) was undertaken, and this led to the synthesis of octafluoro-9(10H)-acridone.3,4 Of more relevance to the work described in detail1 here are reports concerning fluorinated acridones from Russian researchers in the 1970s, notably that (i) thermal treatment of methyl pentafluorophenyl ketone with aniline affords, inter alia, 3-anilino-1,2,4-tri- fluoro-9-methylacridine5 (a reaction extended later to derivatives of aniline6) and (ii) the preparation of 1,2,3,4-tetra- fluoroacridine (1a) from pentafluorobenzaldehyde and the Grignard reagent PhNHMgBr.7 The work reported here stemmed from a serenedipitous discovery, made during mass spectrometric studies on fluorinated Schiff bases,8,9 that condensation of pentafluorobenzaldehyde with p-anisidine under forcing conditions yields 4-methoxy-N-(pentafluorobenzylidene)aniline (4b) contaminated with, inter alia, a product of molecular formula C14H7F4NO.Having shown by X-ray crystallographic analysis12 that the by-product was 1,2,3,4-tetrafluoro-7-methoxyacridine (1b), the generality of the pentafluorobenzaldehyde –primary arylamine reaction as a route to 1,2,3,4-tetrafluoroacridines carrying no 9-substituent has been probed.We have established that 1,2,3,4-tetrafluoroacridine (1a) and a range of 7-substituted analogues (1b–g) can be produced by heating pre-formed Schiff bases (E)-C6F5CH� NC6H4R-p (4a–g) (from C6F5CHO+H2NC6H4R-p) with the parent aniline H2NC6H4R-p (1:1 molar ratio) or a 1: 2 molar mixture of the aldehyde C6F5CHO and the aniline H2NC6H4R-p (R=H, OMe, Me, But, F, Cl and Br) in boiling toluene or, preferably, 1,2-dichlorobenzene. Except where R=But, F, Cl or Br, substantial amounts of the corresponding 3-anilino-1,2,4-trifluoroacridines (7a–e) are also formed.Inter alia, 1,2,3,4-tetrafluoro-6,8-dimethylacridine (11a) and its 3-(3,5-dimethylanilino) derivative (11b) can be obtained by heating pentafluorobenzaldehyde with 2 molar equivalence of 3,5-dimethylaniline at 180 °C in o-C6H4Cl2, while 1-fluoro-7-methoxyacridine (12) is produced under similar conditions from 2,6-difluorobenzaldehyde and p-anisidine · a conversion which heralds numerous extensions envisioned for this new acridine ring synthesis.The formation of 1,2,3,4-tetrafluoroacridines 1a–g is best rationalized in terms of intramolecular ring closure of 2-arylamino derivatives of Schiff bases 4a–g generated in situ via ortho-SNAr attack on those Schiff bases by the arylamines involved. The 19F NMR spectra of tetrafluoroacridines 1a–g and 11a are unexpectedly simple (four equally intense 17 Hz triplets under routine operating conditions, with digital resolution of 1.6 Hz/point).Techniques used: UV, MS, NMR (1H, 19F, 13C) References: 18 Tables: 4 (yields, mps, elemental analyses and spectrsopic data for products of thermal reactions between C6F5CHO and arylamines) Schemes: 4 Received, 11th November 1996; Accepted, 18th November 1996 Paper E/6/07642D References cited in this synopsis 1 Preliminary communication: A. J. Adamson, R. E. Banks and A. E. Tipping, J. Fluorine Chem., 1993, 64, 5. 76 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence.2 P.L. Coe, A. E. Jukes and J. C. Tatlow, J. Chem. Soc. C, 1966, 2020. 3 C. M. Jenkins, A. E. Pedler and J. C. Tatlow, Tetrahedron, 1971, 27, 2557. 4 D. M. Owen, A. E. Pedler and J. C. Tatlow, J. Chem. Soc., Perkin Trans. 1, 1975, 1380. 5 T. N. Vasilevskaya, I. I. Baturina, M. I. Kollegova, T. N. Gerasimova and V. A. Barkhash, J. Org. Chem. USSR, 1971, 7, 1269. 6 T. N. Gerasimova, L. L. Gelumbovskaya, I. I. Baturina and E. P. Fokin, Izv. Sib. Otd. Akad. Nauk SSSR, Ser. Khim. Nauk, 1973 (part 2), 88 (Chem. Abstr., 1973, 79, 53161r). 7 T. N. Gerasimova, N. V. Semikolenova and E. P. Fokin, Izv. Sib. Otd. Akad. Nauk SSSR, Ser. Khim. Nauk, 1977 (part 2), 142 (Chem. Abstr., 1977, 87, 134160g). 8 W. T. Flowers and P. DeFigueredo, unpublished results. 9 D. J. Bell and W. T. Flowers, unpublished results; D. J. Bell, Ph.D. Thesis, University of Manchester, 1987. 12 A. J. Adamson, Y. Archambeau, R. E. Banks, B. Beagley, M. Helliwell, R. G. Pritchard and A. E. Tipping, Acta Crystallogr., Sect. C, 1994, 50, 967. J. CHEM. RESEARCH (S), 1997

ISSN:0308-2342    

DOI:10.1039/a607642d

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

CH C(CONH2)COMe NO2 CH(OH)CH(CONH2)COMe NO2 1 2 78 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 78–79 J. Chem. Research (M), 1997, 0643–0649 2-Hydroxy-2-methyl-2H-1-benzopyran-3-carboxamide Derivatives produced by Knoevenagel Condensation Conor N. O’Callaghan* and T. Brian M. McMurry University Chemical Laboratory, Trinity College, Dublin 2, Ireland The reaction of 2-hydroxybenzaldehydes with 3-oxobutanamide affords 2,4-dihydroxy-2-methyl-2H-3,4-dihydro- 1-benzopyran-3-carboxamides and 2-hydroxy-2-methyl-2H-1-benzopyran-3-carboxamides, depending on the particular aldehyde and the experimental conditions used.Many benzopyran derivatives occur in nature,1 and 2,2-disubstituted 2H-1-benzopyrans are of considerable biological importance. The tocopherol (vitamin E) compounds have been known for many years,2 and more recently 7-methoxy- 2,2-dimethyl-2H-1-benzopyran was shown to inhibit insect hormone activity.3 At present there is widespread interest in the potassium channel modulatory (antihypertensive) activity of a range of 3-hydroxy-2,2-dimethyl-2H-1-benzopyran derivatives, 4 which have been developed following the discovery of cromakalim.5 New 2,2,3-tri- and 2,2,3,4-tetra-substituted benzopyran derivatives, obtained by the reaction of 2-hydroxybenzaldehydes with 3-oxobutanamide, are now reported. 3-Oxobutanamide has been little studied in the Knoevenagel condensation, but it is clearly less reactive than the classical activated methylene derivatives normally cited,6 and is more sensitive to alterations in reaction conditions. Thus, for example, reaction with o-nitrobenzaldehyde under normal basic conditions affords the expected product 1, but in mildly acid solution two diastereoisomeric racemates 2 are obtained.There is a considerable literature describing the Knoevenagel condensations of salicylaldehyde 3a.6,7 With methylene compounds activated by, e.g., C�N and CO2R groups, the reaction affords, almost invariably, coumarin-type products or products derived from these.Initial examination of the reaction of salicylaldehyde with 3-oxobutanamide 4 indicates that it fits into this pattern. Even under very mild Knoevenagel conditions, the only stable, solid product (obtained in very small yield) is the benzopyranopyridine derivative 13 (R=coumarin-3-yl). Under less mild conditions, a complex solid foam is obtained, the two main components of which are the bridged tricyclic derivatives 14 (R=coumarin-3-yl) where Rp=OH and NH2 respectively.All three of these products have previously been shown to be obtained from the reaction of 3-acetyl-2H-1-benzopyran-2-one 10a with ammonia.8 *To receive any correspondence. Scheme 1 a X=H; b X-6-Cl; c X=8-OMe; d X=7-OMe; e X=6,8-Br2; f X=(5,6)-CH�CH·CH�CH (benzopyran numbering)H HO H2NOC O OH Me H In contrast to this, the sole product formed from the reaction of salicylaldehyde with 3-oxobutanamide in ethanol containing acetic acid and minimal piperidine is the crystalline dihydroxy derivative 6a.The observed vicinal coupling constant, 10.5 Hz, for the pyran ring protons H3 and H4 establishes that the latter are trans, with H3 axial and H4 quasiaxial. It is most likely that the 2-hydroxy group is also axial, as shown in Fig. 1 (cf. ref. 9). The fully saturated compound 6a is stable in the solid state and is recrystallisable, but when the [2H6]DMSO NMR solution is stored, it is clear that it undergoes dissociation into the original two components within 48 h.The reaction of 5-chloro-2-hydroxybenzaldehyde 3b with 3-oxobutanamide under similar conditions affords the analogous dihydroxy compound 6b as the main product. NMR confirms this formulation, but shows that in solution in [2H6]DMSO the pyran ring rapidly undergoes ring-opening. Two racemic openchain compounds 5b are present in solution, but these intermediate decomposition products are too unstable to be isolated; further decomposition, with liberation of the original aldehyde, is evident within 2 h.The instability of the compounds 6 in solution is discouraging, but other, substituted o-hydroxybenzaldehydes afford products which are considerably more stable. In contrast to salicylaldehyde and 5-chloro-2-hydroxybenzaldehyde, the reaction of 2-hydroxy-3-methoxybenzaldehyde with 3-oxobutanamide (in methanol containing catalytic piperidine) affords the 2,2,3-trisubstituted product 9c and a little of the coumarin-type product 10c.The compounds 9 and 10 are much more stable than the saturated structures 6 (which are formed without dehydration), and rapid ring-opening and decomposition reactions are not evident. 2-Hydroxy-1-naphthaldehyde behaves like 2-hydroxy- 3-methoxybenzaldehyde, affording the 3,3-disubstituted tricyclic product 12 in moderate yield. Two other aldehydes which afford the same type of product (9e and 9d respectively) but in much smaller yield, are 3,5-dibromo- and 2-hydroxy- 4-methoxybenzaldehyde; in the case of the latter, the 2-oxo derivative 10d is the main product formed.The isolation of the two types of product 9 and 10 shows that the initial condensation can result in the formation of both of the possible stereoisomers 7 and 8. The sequence of formation of the various products can be summarised as shown in Scheme 1. Techniques used: IR, mp, 1H and 13C NMR, elemental analysis References: 12 Schemes: 1 Figures: 1 Received, 29th October 1996; Accepted, 9th December 1996 Paper E/6/07362J References cited in this synopsis 1 E.E. Schwiezer and D. Meeher-Nycz, in Chromenes, Chromanones and Chromones, ed. G. P. Ellis, Wiley, New York, 1977, p. 29. 2 See, e.g. K. Mukai, J. Kageyama, T. Ishida and K. Fukuda, J. Org. Chem., 1989, 54, 552; T. Rosenan and W. D. Habicher, Synlett., 1996, 427. 3 T. R. Kasturi and T. Manithomas, Tetrahedron Lett., 1967, 2573; D. R. Boyd, N. D. Sharma, R. Boyle, T. A. Evans, J. F. Malone, K. M. McCombe, H. Dalton and J. Chima, J. Chem. Soc., Perkin Trans. 1, 1966, 1757. 4 See, e.g., F. Cassidy, J. M. Evans, M. S. Hadley, A. H. Haladi, P. E. Leach and G. Stemp, J. Med. Chem., 1992, 35, 1623. 5 cf. C. J. Roxburgh, Synthesis, 1996, 307. 6 G. Jones, Org. React. (N.Y.), 1967, 15, 204. 7 C. N. O’Callaghan, T. B. H. McMurry and C. J. Cardin, J. Chem. Res., 1990, (S) 132; (M) 0901. 8 C. N. O’Callaghan and T. B. H. McMurry, J. Chem. Res., 1989, (S) 329; (M) 2501. 9 W. D. Cotterill, D. A. Johnston and R. Livingstone, J. Chem. Res., 1995, (S) 226; (M) 1466. 10 N. P. Buu-Hoi, T. B. Loc and N. D. Xuong, Bull. Soc. Chim. Fr., 1957, 561. 11 P. Czerney, H. Hartmann and J. Liebscher, Ger. (East) Pat. 140,252, 1980 (Chem. Abstr., 1980, 93, 114 327). 12 E. Knoevenagel and R. Schroeter, Ber. Dtsch. Chem. Ges., 1904, 37, 4484. J. CHEM. RESEARCH (S), 1997 79 Fig. 1 Probable conformation of the dihydroxy derivat

ISSN:0308-2342    

DOI:10.1039/a607362j

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

C N O C A B N A B C O O D N A B O O D C PhCH CHCOCl N Ar CO2Et CO2Et Ph O N Ph O Ar CO2H N Ph O Ar COCHN2 N Ph O ArNHCH(CO2Et)2 Ar 2 3a,b CO2Me N Ph O 4a,b KOH (2 equiv.) i, SOCl2, benzene Ar Et3N, benzene reflux CO2H EtOH–H2O/reflux ii, CH2N2, ether–CH2Cl2 5a,b 6a,b N O O H H Ar reflux Ag2O, MeOH 7a,b KOH, EtOH–H2O reflux PPA, 100 °C a Ar = p-chlorophenyl b Ar = m-nitrophenyl 8 1a,b + COCl N CO2Et CO2Et Ar O N HO2C O Ar N O Ar N2HC N O Ar MeO2C ArNHCH(CO2Et)2 Et3N, benzene reflux i, SOCl2 N O Ar 11a,b 9 10a,b HO2C 12a,b ii, CH2N2 13a,b 14a,b N O Ar Ag2O, MeOH 2 KOH, acetone–H2O reflux H H KOH, EtOH O reflux reflux 15a,b PPA O 100 °C 1a,b + 80 J.CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 80–81 J. Chem. Research (M), 1997, 0568–0583 Studies on g-Lactams: Synthesis of some 3-Aryl- 1,3a,4,9b-tetrahydrobenzo[e]indole-2,5-dione Derivatives and its Implication in the Total Synthesis of Functionalized 17-Azasteroids Gandhi K. Kar, Dandala Ramesh, Basanta G.Chatterjee and Jayanta K. Ray* Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India The g-lactam esters 3 and 10, prepared from anilinomalonates and 3-arylacryloyl chloride, are hydrolysed and selectively decarboxylated to the trans-acids 4 and 11; further homologation and cyclization produce the tri- and tetra-cyclic g-lactam derivatives 8 and 15 that simulate the B-C-D/A-B-C-D ring system of many azasteroids. g-Lactam moieties, fused to carbocyclic rings, are common in bioactive natural products1,2 and consequently many synthetic strategies have been recorded.3–6 We report here a novel sequence of reactions that synthesise g-lactams with appropriate functionalities for further elaboration and thus construction of azasteroids (Schemes 1 and 2).Our strategy involved the construction of the g-lactam moiety first, the starting materials already having rings B/A+B, followed by the construction of the ring C in the final stage to achieve model and target 17-azasteroids (Fig. 1). Thus condensation of arylaminomalonates 1 with b-arylacryloyl chlorides 2 in the presence of triethylamine extensively produced the g-lactam diesters 3 in good yields (Scheme 1). Saponification with in situ decarboxylation of 3 with alcoholic KOH (2 equiv.) under reflux exclusively produced the trans-acid 4 in excellent yield. The structure was confirmed by spectral data (IR, NMR, MS) and elemental analysis. The trans-geometry was assigned by the coupling constants of 4-H and 5-H (J ca. 4–5 Hz). Annulation of the CO2H side chain was achieved by the Arndt–Eistert method. Thus the g-lactam monoacid 4 was converted into the acid chloride with SOCl2 and subsequent treatment of the acid chloride with diazomethane gave the diazoketone 5 in excellent yield. The *To receive any correspondence. Fig. 1 Scheme 1 Scheme 2J. CHEM. RESEARCH (S), 1997 81 diazoketone when refluxed with Ag2O in MeOH produced the g-lactam ester 6 in 50–70% yield.Trans-stereochemistry of the 4-H and 5-H was proved by X-ray crystallography15 of 6a. Alkaline hydrolysis of the ester 6 gave the acid 7 (78–82%) which when cyclised with PPA (at 100 °C) produced the B-C-D ring simulating an azasteroid, i.e. 3-aryl- 1,3a,4,9b-tetrahydrobenzo[e]indole-2,5-dione in moderate to good yield. Following a similar reaction sequence and starting from an anilinomalonate derivative and 2-(2-naphthyl)acryloyl chloride 9 the high yielding total synthesis of the functionalized 17-azasteroid was achieved (Scheme 2).Anilinomalonates 1 on reaction with 9 in the presence of Et3N produced the g-lactam ester 10 in excellent yields. Compound 10 on hydrolysis (aq. acetone/KOH, 2 equiv., reflux), with decarboxylation followed by homologation of the CO2H sidechain by the Arndt–Eistert method produced 13 in high overall yields. Saponification (KOH/EtOH–H2O, reflux) of 13 afforded the acid 14 which when subjected to cyclization with PPA at 100 °C afforded the 17-azasteroid derivatives 15 in 59–63% yield in the final step of the reaction.The spectroscopic data as well as elemental analysis of the compounds gave satisfactory results. We are grateful to Dr A. K. Patra (University of Calcutta, India), Dr M. Ghosh (Stevens Institute of Technology, USA) and Dr E. Ali (IICB, Calcutta, India) for 1H and 13C NMR and mass spectral data. Thanks are due to DST and CSIR, New Delhi, for financial support. Techniques used: IR, 1H and 13C NMR, MS, elemental analysis Figures: 7 References: 15 Received, 24th April 1996; Accepted, 2nd December 1996 Paper E/6/02882I References cited in this synopsis 1 J. E. Baldwin, G. P. Lynch and J. Pitlik, J. Antibiot., 1991, 44, 1. 2 L. N. Jungheim and R. J. Ternansky, in The Chemistry of b-Lactams, ed. M. I. Page, Blackie, London, 1992, pp. 306– 324. 3 J. E. Baldwin, R. M. Adlington, R. H. Jones, C. J. Schofield, C. Zarocostas and W. C. Greengrass, J. Chem. Soc., Chem. Commun., 1984, 194. 4 J. E. Baldwin, R. T. Freeman and C. J. Schofield, Tetrahedron Lett., 1989, 30, 4011. 5 J. E. Baldwin, C. Lowe and C. J. Schofield, Tetrahedron Lett., 1986, 27, 3461. 6 J. E. Baldwin, M. F. Chan, G. Gallacher, M. Otsuka, P. Monk and K. Prout, Tetrahedron, 1984, 21, 4513. 15 G. K. Kar, B. G. Chatterjee and J. K. Ray, Synth. Commun., 1993, 23, 1953.

ISSN:0308-2342    

DOI:10.1039/a602882i

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

82 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 82–83 J. Chem. Research (M), 1997, 0584–0596 A New Route for the Preparation of Fluorene Derivatives using Friedel–Crafts Intramolecular Cyclobenzylation Takehiko Yamato,* Masayasu Komine and Koji Matsuo Department of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga-shi, Saga 840, Japan A convenient preparation of fluorene derivatives based on a novel Friedel–Crafts intramolecular cyclobenzylation, involving the action of Cl2CHOMe and TiCl4 on a variety of biphenyls (constructed such that electrophilic substitution occurs ortho to the biphenyl linkage), is described.Although there are numerous reports on the synthesis of fluorenes from 2-mono- and 2,2p-di-substituted biphenyls using cyclization reactions,3–5 there has not been any report concerning Friedel–Crafts intramolecular benzylation of 2-halomethylbiphenyls to give fluorenes. Recently we reported6 that the chloromethylation of 4,4p-dimethoxy- 3,3p,5,5p-tetramethylbiphenyl 1b affords the Friedel–Crafts intramolecular benzylation products, 2,7-dimethoxy- 1,3,6,8-tetramethylfluorene derivatives in 20–40% yield.However, the selective preparation of substituted fluorenes using Friedel–Crafts intramolecular cyclobenzylation by the action with chloromethyl methyl ether was very difficult because of low yields as well as their separation from the reaction mixture. On the other hand, Meth-Cohn and coworkers have reported7 that Lewis acid catalysed formylation of diarylmethanes with dichloromethyl methyl ether affords anthracenes by a direct Bradsher reaction. However, this is limited to the preparation of benzothiophene derivatives.This strategy is proposed to be employed for the preparation of fluorene derivatives. Here we report the first success in the formation of a fluorene skeleton via a Friedel–Crafts intramolecular benzylation during the action of Cl2CHOMe and TiCl4 on 4,4p-di-tert-butylbiphenyl 1a and 4,4p-dimethoxy- 3,3p5,5p-tetramethylbiphenyl 1b, which are constructed such that electrophilic substitution occurs ortho to the biphenyl linkage.A series of biphenyls 1a–d was prepared according to previous reports.6,9 On treatment of 1a with Cl2CHOMe (7 equiv.) in the presence of TiCl4 at 0 °C for 5 h, the expected 2,7-di-tert-butyl-9-chloro-4-formylfluorene 5a was obtained in 78% yield along with 2,7-di-tert-butyl-4-formylfluoren- 9-one 6a in 5% yield.The same result was obtained in the case of compound 1b. The reaction was again carried out under the same conditions and the expected 9-chloro-4-formyl-2,7-dimethoxy-1,3,6,8- tetramethylfluorene 5b was obtained in 87% yield. It was also found that treatment of 2,2p,3,3p-tetramethoxybiphenyl 1c with TiCl4 for 24 h under the same conditions as described above resulted only in a quantitative recovery of starting compound. This result indicates that two methoxy groups at the ortho position of compound 1c might disturb the electrophilic substitution at both the 2- and 2p-positions of the biphenyl.Similar treatment of 4,4p-di-tert-butyl-2,2p-dimethylbiphenyl 1d with Cl2CHOMe in the presence of TiCl4 afforded 4,4p-di-tert-butyl-6-formyl-2,2p-dimethylbiphenyl 7 in 70% yield. The present novel intramolecular benzylation reaction is strongly affected by the methyl groups at the 2- and 2p-positions of the biphenyls which are forced to arrange in a conformation appropriate for the subsequent further intramolecular benzylation reaction.However, from consideration of molecular models, 2,2p-dimethylbiphenyl 1d is unlikely to form an intermediate suitable for undergoing intramolecular cyclobenzylation, because a chloromethoxymethyl group at the 6-position would be pushed away from the 6p-position of the other benzene ring in order to avoid crowding between the two methyl groups at the 2- and 2p-positions.The reduction of 5a with chlorohydroalane in diethyl ether afforded the 4-hydroxymethyl derivative 10 in 64% yield. Successive conversion of the hydroxymethyl group to a methyl group was achieved via the chloromethyl derivative. Recently, we have found that Nafion-H, a perfluorinated resin sulfonic acid,10 catalyses Friedel–Crafts benzylations of *To receive any correspondence. Table 1 Formylation of substituted biphenyls 1 with Cl2CHOMe to give fluorenes 5 Run Biphenyl 1 t/h Product 5 (%)a 123 a bc 55 24 a (78)b b (87) d (0)c aIsolated yields.b2,7-Di-tert-butyl-4-formylfluoren-9-one 6a was obtained in 5% yield. cStarting compound 1c was recovered in almost quantitative yield.J. CHEM. RESEARCH (S), 1997 83 benzene and substituted benzenes with benzyl alcohols under relatively mild conditions. The Nafion-H-catalysed transalkylation of 12 in toluene afforded the desired 4-methyl- fluorene 13 in 65% yield together with formation of tertbutyltoluene 14.Trans-alkylation of 12 with Nafion-H catalyst gave a better yield than that achieved with AlCl3–MeNO2 catalyst (30%).12 Although 4-methylfluorene 13 has been prepared by passing 2,2p-dimethylbiphenyl over Pd–charcoal at 450 °C,13 the preparative conditions are very severe as an experimental laboratory procedure in comparison with our method. Furthermore, Kajigaeshi et al.12 have reported the construction of the fluorene skeleton using an Ullmann coupling reaction of 4,4p-di-tert-butyl-2,2p-diiododiphenylmethane.However, the introduction of iodine groups at the 2,2p-positions of 4,4p-di-tert-butyldiphenylmethane seems quite difficult and leads to low product yield and difficult product separation. Utilizing the present novel Friedel–Crafts intramolecular cyclobenzylation reaction we have developed a much more convenient procedure to convert 4,4p-di-tert-butylbiphenyl 1a directly to 4-methylfluorene 13. Consequently, the preparative route to compound 13 can be accomplished in six steps starting from biphenyl.Techniques used: 1H NMR, IR, MS, VPC analysis References: 13 Schemes: 2 Equations: 4 Received, 16th August 1996; Accepted, 9th December 1996 Paper E/6/05730F References cited in this synopsis 3 E. C. Taylor and E. J. Strojny, J. Am. Chem. Soc., 1960, 82, 5198. 4 F. G. Baddar, S. Sherif, L. Ekladios and A. E. Azab, J. Chem. Soc., 1967, 506. 5 W. Reid and D. Freitag, Angew. Chem., Int. Ed. Engl., 1968, 7, 835. 6 T. Yamato, M. Komine, N. Sakaue, T. Matsuda, Y. Nagano and M. Tashiro, J. Chem. Res. (S), 1993, 146. 7 (b) M. Ahmed. J. Ashby, M. Ayad and O. Meth-Cohn, J. Chem. Soc., Perkin Trans. 1, 1973, 1099. 9 (b) T. Yamato, C. Hideshima, K. Suehiro, M. Tashiro, G. K. S. Prakash and G. A. Olah, J. Org. Chem., 1991, 56, 6248. 10 (b) T. Yamato, J. Synth. Org. Chem. Jpn., 1995, 53, 487 and references cited therein. 12 S. Kajigaeshi, T. Kadowaki, A. Nishida and S. Fujisaki, Bull. Chem. Soc. Jpn., 1986, 59, 97. 13 M. Orchin and E. O. Woolfolk, J. Am. Chem. Soc., 1945, 67, 122. Scheme 2

ISSN:0308-2342    

DOI:10.1039/a605730f

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

R Me O R NMe2 O N O O R¢ DMF, DMA 3 O R O R¢COHN 4 a R = Ph b R = 2-thienyl c R = 2-furyl d R = 2-pyridyl e R = 2-naphthyl f R = pyrrol-2-yl a R = R¢ = Ph b R = 2-thienyl, R¢ = Ph c R = 2-furyl, R¢ = Ph d R = 2-pyridyl, R¢ = Ph e R = 2-naphthyl, R¢ = Ph f R = pyrrol-2-yl, R¢ = Ph g R = Ph, R¢ = Me h R = 2-thienyl, R¢ = Me i R = 2-furyl, R¢ = Me j R = 2-naphthyl, R¢ = Me 8 4a–f 5 R NMe2 CN CN O O NMe2 CN NH2 R NH2 O NC R NMe2 NH O R NC CN R NC NMe 9 10 CN CH2 X X = CN X = CONH2 11 13 12 4a–c 9–13a R = Ph b R = 2-thienyl c R = 2-furyl J.Chem. Research (S), 1997, 84–85 J. Chem. Research (M), 1997, 0601–0615 1-Substituted 3-Dimethylaminoprop-2-en-1-ones as Building Blocks in Heterocyclic Synthesis: Routes to 6-Aryland 6-Heteroaryl-2H-pyran-2-ones and 6- and 4-Arylpyridin- 2(1H)-ones Fatima Al-Omran,* Nouria Al-Awadhi, Mervat Mohammed Abdel Khalik, Kamini Kaul, Abdel Abu EL-Khair and Mohammed Hilmy Elnagdi* Department of Chemistry, Faculty of Science, University of Kuwait, PO Box 5969, Safat 13060, Kuwait Several new 6-substituted-3-acylamino-2H-pyran-2-ones 6a–j have been prepared from the reaction of enaminones 4a–f with N-acyl- and N-benzoyl-glycines; the enaminones 4a–c react with malononitrile in ethanol solution and in the presence of a base to yield amides 11a–c which are converted into 6-aryl-1,2-dihydro-2-oxypyridine-3-carbonitriles 13a–c on reflux in acetic acid.In conjunction with our interest in the synthesis of functionally substituted heteroaromatic compounds as potential pharmaceuticals,7–10 the development of an efficient route for the synthesis of 6-aryl- and 6-heteroaryl-2H-pyran-2-ones as potential anti-HIV agents seemed interesting.Recently Kocevar and co-workers12–14 have described a one-pot synthesis of 3-acylaminopyranones by mixing 1,3-dicarbonyl compounds, triethyl orthoformate or dimethylformamide dimethyl acetal and N-acylglycines with a large excess of acetic anhydride.Since this method seemed the simplest way to synthesise our required compounds we investigated the reaction of hippuric acid, dimethylformamide dimethyl acetal and the methyl ketones 3a–f. However, under these conditions only oily mixtures of products were obtained. We thus decided to modify this synthetic approach by first condensing 3a–f with dimethylformamide dimethyl acetal, utilizing a literature procedure for the synthesis of 4a from 3a15 and reacting the produced 1-substituted 3-dimethylaminoprop- 2-en-1-ones 4a–c,e with N-acylglycines.We found that 4a reacts with hippuric acid in refluxing acetic anhydride to yield a product of molecular formula C18H13NO3 which can be formulated as the oxazolone derivative 7a or the pyranone 8a. Structure 8a was established for this product based on the 1H NMR spectrum which revealed an absence of any signals for sp3 carbons at d 3.0–5.0 but showed two doublets at d 7.16 and 8.22 for the pyranone 5-H and 4-H, respectively.Similarly the reaction of 4b–f with hippuric acid afforded the pyranones 8b–f. When 4a–c,e were refluxed with glycine in the presence of acetic anhydride the pyranones 8g–j were obtained in good yields. It is assumed that acetyl glycine generated in situ is cyclised into 5b which then reacts with 4a–c,e yielding the final isolable 8g–j. The 1H NMR spectra of all compounds 8a–j revealed characteristic doublets for 4-H and 5-H with J=8 Hz. The formation of 8a-j from 4a–f with either N-acylglycines or hippuric acid can thus be considered as an extension of the Kepe pyranone synthesis12–14 to enable the synthesis of 6-aryl- and 6-heteroaryl-pyran- 2-ones.Compounds 4a–c reacted with malononitrile in ethanol and in the presence of a base, affording 1:1 adducts. We first assigned the pyran structures 10a–c for these products, by assuming initial formation of the Michael adducts 9a–c and subsequent cyclization. However, the 1H NMR spectrum for compound 11b, for example, revealed a two-proton doublet at d 5.77 and 7.23 with a J value of 13 Hz which can be only attributed to trans olefinic protons.We therefore considered structures 11a–c for these reaction products. They are assumed to be formed via initial hydrolysis of malononitrile to cyanoacetamide by water present in the solvent. This was followed by condensation of the active methylene group with the carbonyl of compounds 4a–c. Water eliminated in the reaction then hydrolyses a further amount of malononitrile and the reaction can thus proceed to completion.This structure was confirmed by preparing the same reaction products via condensation of cyanoacetamide with 4a–c under the same reaction conditions. Furthermore, compounds 11a–c were converted into the pyridinones 13a–c which were also obtained by hydrolysis of 3 - a r y l - 2 - c y a n o - 5 - d i m e t h y l a m i n o - 2 , 4 - p e n t a - 2 , 4 - d i e n e n i t r i l e s 12a–c by the action of acetic acid–hydrochloric acid mixture.Attempts to prepare 11a–c by direct hydrolysis of 12a–c, recently obtained in our laboratory,21 in ethanol–piperidine for 24 h, failed, thus supporting the assumption that cyanoacetamide and not malononitrile is the reactive species in this reaction. 84 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence.R O NMe2 HN O CN R CN CONH2 14 4a,b NaOEt a R = Ph b R = 2-thienyl In contrast to the observed formation of the pyridinones 13a–c, treatment of 4a,b with cyanoacetamide in sodium ethoxide solution afforded the pyridinones 14a,b.This work was financed by University of Kuwait Research grants SC 055 and SC 071. We are grateful to the general facility projects at the Chemistry Department, Faculty of Science, University of Kuwait, for analytical and spectral measurements. Techniques used: IR, 1H and 13C NMR, mass spectrometry References: 21 Received, 31st July 1996; Accepted, 10th December 1996 Paper E/6/05368H References cited in this synopsis 7 H.Al-Awadhi, F. Al-Omran, M. H. Elnagdi, L. Infants, C. Foces- Foces, N. Jagerovic and J. Elguero, Tetrahedron, 1995, 51, 12 745. 8 M. H. Elnagdi, A. H. Elghandour, M. K. A. Ibrahim and I. S. A. Hafiz, Z. Naturforsch., 1992, 476, 572. 9 F. A. Abou-Shanab, M. H. Elnagdi, F. M. Ali and B. J. Wake- field, J. Chem. Soc., Perkin Trans. 1, 1994, 1449. 10 M. H. Elnagdi and A. W. Erian, Arch. Pharm. (Weinheim, Ger.), 1991, 324, 853. 11 J. D. Hepworth, in Comprehensive Heterocyclic Chemistry, ed. A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford, 1984, vol. 3, pp. 737–883. 12 V. Kepe, M. Kocevar and S. Polance, Heterocycles, 1995, 41, 1299. 13 M. Kocevar, S. Polance, B. Vercek and M. Tisler, Liebigs Ann. Chem., 1990, 501. 14 V. Kepe, M. Kocevar, S. Polance, B. Vercek and M. Tisler, Tetrahedron, 1990, 46, 1081. 15 S. Tseng, J. W. Epstein, H. J. Brbander and G. Francisco, J. Heterocycl. Chem., 1987, 24, 837. 16 A. A. Elagamey, F. M. A. El Taweel, S. Z. A. Sowellium, M. A. Sofan and M. H. Elnagdi, Collect. Czech. Chem. Commun., 1990, 55, ???. 17 M. H. Elnagdi, R. M. Abdel-Motaleb, M. Mustafa, M. F. Zayed and E. M. Kamel, J. Heterocycl. Chem., 1987, 24, 1677. 28 C. P. Dell, T. J. Howe and W. C. Prowe, J. Heterocycl. Chem., 1994, 31, 749. 19 B. J. N. Martin, A. Martinez-Grau and C. Seoane, J. Heterocycl. Chem., 1995, 32, 1381. 20 N. M. Abed, N. S. Ibrahim and M. H. Elnagdi, Z. Naturforsch., 1986, 416, 925. 21 F. Al-Omran, M. M. Abdel Khalik and M. H. Elnagdi, Heteroatom Chem., 1995, 6, 545. J. CHEM. RESEARCH (S), 1997 85

ISSN:0308-2342    

DOI:10.1039/a605368h

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

86 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 86–87 J. Chem. Research (M), 1997, 0616–0642 Syntheses of Some 1,2- and 1,4-Dihydropyridines and X-Ray Crystal Structures of 1-Dimethylamino- 5-ethoxycarbonyl-1,4-dihydro-3-methoxycarbonyl-2-methyl- 4-phenylpyridine, 3-Cyano-3,4-dihydro-5-methoxycarbonyl- 6-methyl-4-phenylpyridin-2(1H)-one and 5-Ethoxycarbonyl-1,4-dihydro-3-methoxycarbonyl- 1,2-dimethyl-4-phenylpyridine Max D. Pendleton,a Roy L. Beddoes,a Neil J. Andrew,a Michael Butters*b and John A.Joule*a aChemistry Department, The University of Manchester, Manchester M13 9PL, UK bProcess Research and Development, Pfizer Central Research, Sandwich, Kent CT13 9NG, UK We describe a synthesis of an a-unsubstituted 1,4-dihydropyridine 10 and its 1,2-dihydro isomer, and crystal structures of 10 and some by-products 5 and 6 obtained during the ring synthesis. Considerable interest in the synthesis of 1,4-dihydropyridines derives from their activity as calcium antagonists and thus for the development of drugs for the treatment of cardiovascular diseases.4 1,4-Dihydropyridines are also candidates for the treatment of multidrug resistance (MDR) during cancer chemotherapy,6 as possible thromboxane synthetase inhibitors, 7 PAF-acether antagonists,8 and antithrombotic-antihypertensive agents.10 An alternative to the usual means for the synthesis of 1,4-dihydropyridines2 is the partial reduction11 of pyridinium salts.The addition of 1,1-dimethylhydrazine to ethyl propiolate produced the imine 2, condensation of which with benzaldehyde provided the hydrazone 3.The heterocyclic ring was produced by the reaction of 3 with methyl 3-aminocrotonate in hot acetic acid giving the dihydropyridine 4 accompanied by two other compounds, the structures of which were established by X-ray determinations: 5 and 6. Oxidation of 4 with cerium(IV) ammonium nitrate17 produced 7, subsequent quaternisation giving the salt 8.Reduction of the salt 8 with sodium borohydride in the presence of sodium carbonate produced the 1,2-dihydropyridine 9, whereas reduction with sodium dithionite gave a mixture of the 1,4-dihydropyridine 10 (62%) with 9 (20%). X-ray Crystallography.·Data from crystals (5, approx. 0.30Å0.45Å0.56 mm; 6, 0.40Å0.42Å0.60 mm; 10, 0.25Å 0.35Å0.50 mm) were obtained using a Rigaku AFC5R diffractometer with graphite-monochromated CuKa radiation and a 12 kW rotating anode generator. Structures were solved by direct methods.19 All calculations were performed using the TEXSAN crystallographic software package.21 Data for 5.·There were 2982 unique (Rint=0.049) reflections in the 3134 collected.The final cycle of full-matrix leastsquares refinement was based on 2450 observed reflections [Ia3.00s(I)] and 227 variable parameters and converged (largest parameter shift was s0.01 times its esd) with unweighted and weighted agreement factors of R=0.064 and Rw=0.086.The standard deviation of an observation of unit weight was 3.50. Crystal data for 5. Colourless, prismatic, monoclinic, M, 344.41; V=1873.5(2) Å3; a=12.404(1), b=9.5640(6), c=15.8180(0) Å; b=93.260(6)°; space group P21/n (No. 14); Z=4; Dcalc=1.221 g cmµ3; F(000)=736; h, 0 to 13, k, 0 to 10, l, µ17 to 17. Data for 6.·There were 2182 unique (Rint=0.049) reflections in the 2341 collected. The final cycle of full-matrix leastsquares refinement was based on 1589 observed reflections [Ia3.00s(I)] and 182 variable parameters and converted (largest parameter shift was s0.01 times its esd) with unweighted and weighted agreement factors of R=0.086 and Rw=0.130.The standard deviation of an observation of unit weight was 5.57. *To receive any correspondence.J. CHEM. RESEARCH (S), 1997 87 Crystal data for 6. Colourless prismatic, monoclinic, M, 270.29; V=1393.2(4) Å3; a=13.581(2), b=11.6960(8), c=8.7717(6) Å; b=90.700(8)°; space group P21/c (No. 14); Z=4; Dcalc=1.288 g cmµ3; F(000)=568; h, µ15 to 15, k, µ13 to 9, l, µ8 to 9. Data for 10.·There were 2462 unique (Rint=0.102) reflections in the 2621 collected. The final cycle of full-matrix least-squares refinement was based on 2168 observed reflections [Ia3.00s(I)] and 208 variable parameters and converged (largest parameter shift was s0.01 times its esd) with unweighted and weighted agreement factors of R=0.071 and Rw=0.103. The standard deviation of an observation of unit weight was 4.39.Crystal data for 10. Colourless, prismatic, triclinic, M, 315.37; V=831.0(2) Å3; a=10.279(1), b=13.837(2), c=5.921(1) Å; a=95.28(1), b=93.260(6), g=83.489(9)°; space group P�1 (No. 2); Z=2; Dcalc=1.260 g cmµ3; F(000)=336; h, µ8 to 11, k, µ15 to 15, l, µ6 to 6. We thank the EPSRC and Pfizer Central Research, UK, for CASE awards (to M. D. P. and N. J. A.) and support, and the SERC for funds for the purchase of the Rigaku AFC-5R diffractometer. Techniques used: IR, UV, 1H NMR, mass spectrometry, X-ray crystallography References: 22 Schemes: 1 Tables 1–9: Positional parameters and B(eq) values, intramolecular distances (non-hydrogen atoms) and intramolecular bond angles (non-hydrogen atoms) for 5, 6 and 10 Received, 22nd October 1996; Accepted, 13th December 1996 Paper E/6/07198H References cited in this synopsis 2 A.Hantzsch, Liebigs Ann. Chem., 1892, 215, 1. 4 F. Bossert, H. Meyer and E. Wehinger, Angew. Chem., Int. Ed. Engl., 1981, 20, 762; F.Bossert and W. Vater, Med. Res. Rev., 1989, 9, 291; S. Goldman and J. Stoltefuss, Angew. Chem., Int. Ed. Engl., 1991, 30, 1559; G. C. Rovnyak, S. D. Kimball, B. Beyer, G. Cucinotta, J. D. DiMarco, J. Gougoutas, A. Hedberg, M. Malley, J. P. McCarthy, R. Zhang and S. Moreland, J. Med. Chem., 1995, 38, 119. 6 K. Ohsumi, K. Ohishi, Y. Morinaga, R. Nakagawa, Y. Suga, T. Sekiyama, Y. Akiyama, T. Tsuji and T. Tsuruo, Chem. Pharm. Bull., 1995, 43, 818. 7 C. Ennis, S.E. Granger, V. C. Middlefell, M. E. Philpot and N. B. Shepperson, J. Cardiovasc. Pharmacol., 1989, 13, 511. 8 C. E. Sunkel, M. F. de Casa-Juana, L. Santos, M. M. G�omez, M. Villarroya, M. A. Gonz�alez-Morales, J. G. Priego and M. P. Ortega, J. Med. Chem., 1990, 33, 3205. 10 J. L. Archibald, G. Bradley, A. Opalko, T. J. Ward, J. C. White, C. Ennis and N. B. Shepperson, J. Med. Chem., 1990, 33, 646. 11 Key references are: W. Hanstein and K. Wallenfels, Tetrahedron, 1967, 23, 585; F. W. Fowler, J. Org. Chem., 1972, 37, 1321; E. Booker and U. Eisner, J. Chem. Soc., Perkin Trans. 1, 1975, 929; E. E. Knaus and K. Redda, Can. J. Chem., 1977, 55, 1788; D. L. Comins and N. B. Mantlo, J. Org. Chem., 1986, 51, 5456; K. Wallenfels, H. Schuly and D. Hofmann, Liebigs Ann. Chem., 1959, 621, 106; W. S. Caughey and K. A. Schellenberg, J. Org. Chem., 1966, 31, 1978; J.-F. Biellmann and H. J. Callot, Bull. Soc. Chim. Fr., 1969, 1299; Y.-S. Wong, C. Marazano, D. Gnecco and B. C. Das, Tetrahedron Lett., 1994, 35, 707. 17 J. R. Pfister, Synthesis, 1990, 689. 19 G. M. Sheldrick, SHELX-86, Universities of York and Louvain, 1985. 21 TEXSAN-TEXRAY Structure Analysis Package, Molecular Structure Corporation, 1985. Fig. 1 ORTEP plot of 5 Fig. 2 ORTEP plot of 6 Fig. 3 ORTEP plot

ISSN:0308-2342    

DOI:10.1039/a607198h

出版商:RSC    

年代:1997

数据来源: RSC