摘要:

J. Chem. Research (S), 1997, 33 J. Chem. Research (M), 1997, 0314–0320 The Total Synthesis of Salvinolone Yuan Tian,a Ning Chen,a Hui Wang,a Xin-Fu Pan,*a Xiao-Jiang Haob and Chang-Xiang Chenb aDepartment of Chemistry, National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China bLaboratory of Phytochemistry, Kunming Institute of Botany, Academia Sinica, Kunming 650204, P. R. China Salvinolone 1 is synthesized in seven steps starting from the readily available enone 3.Based on our previous studies on the syntheses of tricyclic diterpenes we now report the total synthesis of salvinolone 11 which is a natural abietane-type diterpene. As shown in Scheme 1, the known3 enone 3 was methylated by MeLi to afford compound 4 which was reduced by NaBH4 in the presence of CeCl3 .7H2O4 to afford the corresponding unsaturated alcohol 5. Stereoselective cyclization of 5 with a solution of phosphorus pentoxide in methanesulfonic acid5 gave an inseparable mixture of diastereoisomers. A 3 :1 ratio of trans-isomer 6a to cis-isomer 6b was shown in the 1H NMR spectrum.The stereochemistry of the cis-fused AB rings in 6b was indicated by characteristic signals at 0.85 ppm.6 Catalytic hydrogenation of 6 by 5% Pd–C afforded a mixture of 7a and 7b which was directly oxidized with CrO3–HOAc–H2O.7 In this oxidation, the trans-fused 7a was converted into the monoketone 8 and the cis-fused 7b was converted into the diketone 9.Then, 8 was refluxed with DDQ10 in methanol to give a,b-unsaturated ketone 10. Conversion of 10 into the target compound 1 was achieved by deprotection with BBr3.11 Techniques used: IR, 1H NMR, MS, column chromatography, TLC References: 11 Schemes: 3 Received, 19th August 1996; Accepted, 29th October 1996 Paper E/6/05751I References cited in this synopsis 1 L. Z. Lin, G. Blasko and G. A. Cordell, Phytochemistry, 1989, 28, 177. 3 X. L. Wang, Y. X. Cui and X. F. Pan, Tetrahedron Lett., 1994, 35, 423. 4 J. L. Luche, J. Am. Chem. Soc., 1978, 100, 2226. 5 B. W. Axon, B. R. Davis and P. D. Woodgate, J. Chem. Soc., Perkin Trans. 1, 1981, 2956. 6 E. Wenkert, A. Afonso, P. Berk, R. W. J. Carney, P. W. Jeffs and J. D. McChesney, J. Org. Chem., 1965, 30, 713. 7 R. Zhou, X. F. Wang, Y. Tian and X. F. Pan, Chin. Chem. Lett., 1995, 6, 657. 10 J. W. A. Findlay and A. B. Turner, J. Chem. Soc. C, 1971, 547. 11 J. F. Mcomie, M. L. Watts and D. E. West, Tetrahedron, 1968, 24, 2289. J. CHEM. RESEARCH (S), 1996 33 *To receive any correspondence. Scheme 1 Reagents and conditions: i, MeLi (100%); ii, NaBH4, CeCl3.7H2O (80%); iii, P2O5, MeSO3H (95%); iv, H2, 5% Pd–C (100%); v, CrO3–HOAc–H2O (22 and 70%); vi, DDQ, MeOH (87%); vii, BBr3 (33%)

ISSN:0308-2342    

DOI:10.1039/a605751i

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 34 J. Chem. Research (M), 1997, 0321–0335 Photocycloaddition of Cyanoethylenes onto 1,4-Dihydroand 1,4,5,6-Tetrahydro-pyridines Donato Donati, Stefania Fusi and Fabio Ponticelli* Istituto di Chimica Organica, Universit`a di Siena, pian dei Mantellini, 44, 53100 Siena, Italy The photochemical cycloaddition of cyanoethylenes onto the title compounds to give 2-azabicyclo[4.2.0]octanes shows a different degree of selectivity depending on the position of the chiral centre of the starting material, with a maximum effect in the case of the 4-position.Previously we reported that some enantiomeric induction is observed during the photoaddition of acrylonitrile onto 1,4-dihydropyridines carrying an easily removable tetraacetylglucoside substituent at the 1-position.1. In view of the continued interest in asymmetric synthesis, we now report a further insight into the above reaction, by considering the effect of the location of the chiral centre with respect to the C(2)–C(3) double bond.Photochemical addition of acrylonitrile onto dihydropyridine 2 followed by catalytic hydrogenation of the reaction mixture yielded two pairs of the diastereoisomeric amides, 3 and 4, with a low diastereoisomeric excess (d.e.) (5–15%). We then considered the 1,4-dibenzyl-1,4-dihydropyridine 5, but found it not suitable for our aims since upon irradiation it rearranges to the 1,6-dibenzyl-1,6-dihydropyridine 7. However, catalytic hydrogenation of 5 gave the tetrahydro derivative 8, which by acrylonitrile photoaddition gave nearly exclusively the 8-cyano-2-azabicyclo[4.2.0]octanes 11 and 12, showing a high degree of regio- and stereo-chemical control due to the 4-substituent.The structures of compounds 11 and 12 were assigned on the basis of 1H and 13C NMR chemical shift considerations and NOE experiments. In view of the synthetic potential of this reaction, a deeper insight into the mechanism was required.To this purpose we verified that the reaction requires a non-symmetrically substituted electron-deficient alkene. In fact, neither fumaronitrile nor vinyl ether underwent photoaddition onto 1,4-dihydropyridines. In addition, when we irradiated ethyl 1-benzyl- 1,4-dihydronicotinate in the presence of (Z)- or (E)-but- 2-enenitrile we obtained, after hydrogenation, the 2-azabicyclo[4.2.0]octanes 13, 14 or 15, 16, respectively. It is worth noting that the cross-over products, i.e. 13, 14 from the E-isomer or 15, 16 from the Z-isomer, were not formed. The structures of the above compounds were assigned on the basis of NMR, NOE and observed and calculated10 LIS data. In conclusion, alkene geometry is retained during the photoaddition onto the pyridine system, suggesting a concerted process and excluding long-lived radicals as intermediates. We thank the Ministero dell’Universit`a e della Ricerca Scientifica e Tecnologica, Rome (quota 60%) for financial support and Dr G.L. Giorgi, Centro di Analisi e Determinazioni Strutturali, University of Siena, Italy, for the recording of mass spectra. Techniques used: 1H and 13C NMR, IR, polarimetry, MS and HRMS References: 10 Schemes: 4 Figure 1: Stereoview of the conformation of 14 Table 1: 1H NMR data for 2-azabicyclo[4.2.0]octanes 3, 4, 11–18 Table 2: 13C NMR data for 2-azabicyclo[4.2.0]octanes 3, 4, 11–18 Table 3: Observed and calculated LIS data for 13–18 (17 and 18 are stereoisomers of 14/16). Received, 30th July 1996; Accepted, 29th November 1996 Paper E/6/05331I References 1 G. Adembri, D. Donati, S. Fusi and F. Ponticelli, J. Chem. Soc., Perkin Trans. 1, 1992, 2033. 10 J. Paasivirta, in Lanthanide Shift Reagents in Stereochemical Analysis, VCH, New York, 1986, pp. 119–126, 145–150. 34 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence. Scheme 1 Reagents and conditions: i, CH2�CHCN, hv; ii, H2 Scheme 2 Reagents and conditions: i, H2/Pd; ii, hv; iii, CH2�CHCN, hv Scheme 3 Conditions: i, irradiation with (Z)-but-2-enenitrile, catalytic hydrogenation; ii, irradiation with (E)-but-2-enenitrile, catalytic hydrogena

ISSN:0308-2342    

DOI:10.1039/a605331i

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 35 J. Chem. Research (M), 1997, 0355–0374 The Hydration of Indane-1,2,3-triones and Related Triones Keith Bowden* and Sanjay Rumpal Department of Biological and Chemical Sciences, Central Campus, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK A series of 5-mono- and 5,6-di-substituted indane-1,2,3-triones, phenalene-1,2,3-trione and 1,3-diphenylpropane- 1,2,3-trione form 2,2-dihydroxy-1,3-dione hydrates; the rates for the uncatalysed hydrations were measured and the structure of the transition state is elucidated from activation parameters, the kinetic role of water, and solvent isotope and substituent effects.The hydration of mono- and di-substituted indane- 1,2,3-triones (2), as well as of phenalene-1,2,3-trione and 1,3-diphenylpropane-1,2,3-trione, was investigated. The equilibrium constants and rate coefficients for mono-hydration, KH and k1, respectively, to form the substituted 2,2-dihydroxyindane- 1,3-diones (1) were estimated or measured.The results from 1H NMR and UV–VIS spectroscopic studies indicate that, in 0.7–96.7% (v/v) dioxane–water, the triones are almost completely (i.e. a98%) hydrated, cf. ref. 2. The rate coefficients, k1, for the uncatalysed hydration in dioxane–water (96.7%, v/v) were measured at 25.0, 35.0 and 45.0 °C. The activation parameters were evaluated with DH‡ between 4.0 and 6.6 kcal molµ1 and DS‡ between µ54 and µ46 cal molµ1 Kµ1. The effect of water content on the hydration rates in aqueous dioxane at 25.0 °C was studied.A plot of log k1 against log [H2O] was linear with a slope of 2.06. The kinetic solvent isotope effect, kH2O/kD2O, in dioxane–water (96.7%, v/v) was found to be 1.65 for 2a (X=Y=H). These results indicate two strongly hydrogen-bonded water molecules in the transition state and are very similar to the results found for dialdehydes.5 The application of a modified Hammett equation to the hydration of 2 gave a Hammett reaction constant (r) of ca. 1.05 in 96.7% aqueous dioxane at 25.0 °C. The latter indicates a significant extent of negative charge development at the reaction site in the transition state, relative to the initial state. A pathway is shown in the Scheme for the hydration of the triones with the transition state having one water molecule attacking the carbonyl group as a nucleophile and a second water molecule acting as a general acid– base catalyst transferring protons. Techniques used: UV–VIS, 13C NMR References: 25 Scheme: 1 Table 1: 13C NMR chemical shifts for the substituted indane- 1,2,3-triones and hydrates in [2H6]Me2SO Table 2: Rate coefficients (k1) for the hydration of substituted indane-1,2,3-triones in dioxane–water (96.7%, v/v) Table 3: Activation parameters for the hydration of substituted indane-1,2,3-triones in dioxane–water (96.7%, v/v) at 30.0 °C Table 4: Rate coefficients (k2) for the hydration of indane- 1,2,3-trione in aqueous dioxane at 25.0 °C Table 5: Hammett reaction constants (r) for the uncatalysed hydration of indane-1,2,3-triones in dioxane–water (96.7%, v/v) at 25.0 °C Table 6: The physical constants of the previously unreported substituted 2,2-dihydroxyindane-1,3-diones Table 7: The physical constants of the previously unreported substituted indane-1,2,3-diones Received, 25th October 1996; Accepted, 31st October 1996 Paper E/6/07281J References cited in this synopsis 2 W.Knoche, H. Wendt, M.-L. Ahrens and H. Strehlow, Collect. Czech. Chem. Commun., 1966, 31, 388. 5 K. Bowden, F. A. El-Kaissi and N. S. Nadvi, J. Chem. Soc., Perkin Trans. 2, 1979, 642; F. Anvia and K. Bowden, J. Chem. Soc., Perkin Trans. 2, 1990, 2093. J. CHEM. RESEARCH (S), 1997 35 *To receive any correspondence. Scheme

ISSN:0308-2342    

DOI:10.1039/a607281j

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 36–37 J. Chem. Research (M), 1997, 0301–0313 Synthesis of Enantiopure 4-Amino-6-fluoro- 3-(hydroxymethyl)chromanes via Intramolecular Nitrone Cycloadditions Gianluigi Broggini,a Luca Bruch�e,*b Enrico Cappellettia and Gaetano Zecchia aDipartimento di Chimica Organica e Industriale, Universit`a, via Golgi 19, 20133 Milano, Italy bDipartimento di Chimica, Politecnico, via Mancinelli 7, 20131 Milano, Italy Enantiopure 4-amino-6-fluoro-3-(hydroxymethyl)chromanes are synthesised starting from 5-fluorosalicylaldehyde and using (R)-(+)-(1-phenylethyl)hydroxylamine as chiral auxiliary. 4-Aminochromane derivatives are becoming increasingly utilised in the medicinal chemistry field of potassium channel openers,1–5 and the fundamental role of the absolute con- figuration in their physiological activity is well documented. 6–9 In a continuation of our research aimed at the synthesis of fluorinated heterocyclic compounds via intramolecular nitrone cycloadditions,10 we describe here a version of this strategy leading to enantiopure 4-amino-6-fluoro- 3-(hydroxymethyl)chromanes. Nitrones derived from allyl-type ethers of 5-fluorosalicylaldehyde and (R)-(+)-(1-phenylethyl)hydroxylamine (1) were envisioned as appropriate intermediates.Accordingly, 36 J. CHEM. RESEARCH (S), 1996 *To receive any correspondence. Scheme 1 Reagents and conditions: i, CaCl2, toluene, reflux; ii, H2, Pd/C, acetic acid, r.t. Scheme 2 Reagents and conditions: i, CaCl2, toluene, reflux; ii, H2, Pd/C, acetic acid, r.t.we synthesised compounds 2 and 8 and treated them with hydroxylamine 1, Schemes 1 and 2.Hydrogenolytic treatment of the cycloadducts resulted in both the removal of the benzyl-like N-pendant and the cleavage of the isoxazolidine ring, so disclosing the masked functionalities and resulting in the optically active amino alcohols 6, 7, 14–17, as three pairs of enantiomers. Their enantiomeric purity was proven to be E98% by NMR analysis in the presence of (R)-O-acetylmandelic acid.We thank the C.N.R. (Rome) and the MURST for financial support. Techniques used: IR, 1H NMR, mass spectrometry, microanalysis, polarimetry References: 14 Schemes: 2 Received, 27th September 1996; Accepted, 22nd October 1996 Paper E/6/06616J References cited in this synopsis 1 V. A. Ashwood, R. E. Buckingham, F. Cassidy, J. M. Evans, E. A. Faruk, T.C. Hamilton, D. J. Nash, G. Stemp and K. Willcocks, J.Med. Chem., 1986, 29, 2194; J. M. Evans and G. Stemp, Chem. Br., 1991, 439. 2 A. H. Weston, in The Pharmacology of Antihypertensive Therapeutics, ed. D. Ganter and P. J. Mulrow, Springer, Heidelberg, 1989, p. 643. 3 D. W. Robertson and M. I. Steinberg, J. Med. Chem., 1990, 33, 1529. 4 N. Taka, H. Koga, H. Sato, T. Ishizawa, T. Takahashi and J. Imagawa, Biomed. Chem. Lett., 1994, 4, 2893. 5 C. Z. Ding and A. V. Miller, Tetrahedron Lett., 1996, 37, 4447. 6 M. R. Attwood, B. S. Brown, R. M. Dansdon, D. N. Hurst, P. S. Jones and P. B. Kay, Biomed. Chem. Lett., 1992, 2, 229. 7 R. M. Soll, P. J. Dollings, R. J. McCaully, T. M. Argentieri, N. Lodge, G. Oshiro, T. Colatsky, N. W. Norton, D. Zebick, C. Havens and N. Halaka, Biomed. Chem. Lett., 1994, 4, 769. 8 R. C. Gadwood, L. M. Thomasco, V. E. Groppi, B. A. Burnett, S. J. Humphrey, M. P. Smith and W. Watt, Biomed. Chem. Lett., 1995, 5, 2101. 9 T. H. Brown, C. A. Campbell, W. N. Chan. J. M. Evans, R. T. Martin, T. O. Stean, G. Stemp, N. C. Stevens, M. Thompson, N. Upton and A. K. Vong, Biomed. Chem. Lett., 1995, 5, 2563. 10 A. Arnone, L. Bruch�e, L. Garanti and G. Zecchi, J. Chem. Res. (S), 1995, 282; A. Arnone, P. Bandiera, P. Bravo, L. Bruch�e and M. Zanda, Gazz. Chim. Ital., 1996, 126, 773. J. CHEM. RESEARCH (S), 1

ISSN:0308-2342    

DOI:10.1039/a606616j

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 38–39 J. Chem. Research (M), 1997, 0344–0354 Conformational Strains of (Z,Z)-, (E,Z)- and (E,E)-1,2,5,6-Tetrathiacycloocta-3,7-dienes based on ab initio Molecular Orbital Calculations Toshio Shimizu,a Kazuko Iwata,a Nobumasa Kamigata*a and Shigeru Ikutab aDepartment of Chemistry, Faculty of Science, Tokyo Metropolitan University, Minami-ohsawa, Hachioji, Tokyo 192-03, Japan bComputer Center, Tokyo Metropolitan University, Minami-ohsawa, Hachioji, Tokyo 192-03, Japan A comparison of the conformations and energies of (Z,Z)-, (E,Z)- and (E,E)-1,2,5,6-tetrathiacycloocta-3,7-dienes based on ab initio MO calculations is reported.Several conformational studies of cycloocta-1,5-diene have been reported based on forcefield calculations.2 We have also reported the conformational study of cycloocta-1,5-diene by ab initio molecular orbital calculations.3 Recently our interest has focused on the conformations of heterocyclic unsaturated compounds.More recently, we succeeded in isolating (Z,Z)-1,2,5,6-tetrathiacycloocta-3,7-diene (1,2,5,6-tetrathiocine) (1), and the conformation in the crystalline state was determined by X-ray crystallography.7 Here we report the conformations and strain energies of 1,2,5,6-tetrathiacycloocta- 3,7-diene through the Z,Z-1, E,Z-2 and E,E-3 isomers based on ab initio molecular orbital calculations. Six local minima were found for the Z,Z-1, E,Z-2 and E,E-3 isomers (Fig. 1). The twist conformer (1-T) of the Z,Z-isomer was calculated to be at a local minimum, in contrast to the corresponding twist conformer of cycloocta- 1,5-diene3 which by frequency analysis indicated the transition state.Furthermore, we attempted to optimize the chair conformer of the E,E-isomer 3 because the chair conformer of (E,E)-cycloocta-1,5-diene was found to lie at the local minimum.3 However, frequency analysis of the chair conformer of 3 showed one imaginary number assigned to be the transition state in the pathway from 3-TC to the other enantiomer of 3-TC.The trans-olefin moieties (S–C�C–S) for the E,Z- and E,E-isomers 2,3-T and 3-TC are twisted from the strain-free horizontal geometry: 144.9, 152.8 and 153.0° (average), respectively. These torsional strains are moderate compared with those of cycloocta-1,5-diene; 131–135°.3 The most interesting point of the conformations of the title compound is the twisted geometries around the sulfur–sulfur bonds. The torsional angles (C–S–S–C) of 3-T and 3-TC for the E,E-isomer are strongly reduced: 48.7 and 23.0°, respectively, corresponding to an increase in the sulfur–sulfur bond lengths.The twist conformer 1-T of the Z,Z-1 isomer was calculated to have the lowest potential energy among all the conformers at the local minima, as shown in Table 2 together with relative energies for cycloocta-1,5-diene. The calculated geometry of 1-T is in good agreement with the X-ray structure of 1 recently determined by us.7 The crystal structure of 1 was therefore the most stable form.The conformers of the E,E-isomer 3 were found to lie at higher energy levels, possibly because of the existence of ring strains. In order to estimate the strain energies of the olefin moieties, we calculated the torsional strain energies for the restricted geometries of but-2-ene as a model. The strain energies depend on the torsional strains around the olefin moieties for the six conformers 1-T, 1-C, 1-HC, 2, 3-TC and 3-TC and are 0.0, 0.0, 0.0, 5.0, 5.0 and 5.0 kcal molµ1, respectively.These strain energies for the E,Z-2 and E,E-3 isomers (5.0 kcal molµ1) are smaller than those for the corresponding geometries of cycloocta-1,5-diene.3 The torsional strains around the sulfur– sulfur bonds were also estimated using dimethyl disulfide as a model. The torsional strains of the disulfide units for the six conformers are 1.4, 1.2, 3.4, 4.3, 7.4 and 17.8 kcal molµ1, respectively.It was found that the torsional strains of the disulfide units for the conformers of the E,E-3 isomer are unexpectedly large compared with those of the olefin moieties in this ring system. The remaining relative energies after deduction of these torsional strain energies for the six conformers, relative to that of 1-T, are 0, 5.5, 9.8, 3.5, 3.0 and 1.8 kcal molµ1, respectively. As a result, the energy differ- 38 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence.Fig. 1 Optimized geometries for (Z,Z)-1, (E,Z)-2 and (E,E)-3 at the local minimaences for 1-T, 2, 3-T and 3-TC are explained by the strain energies caused by the torsional strains of the olefin moieties and the disulfide units. The remaining energy for 1-HC may be explained by bond angle strains. The bond angles of S(4)–C(5)–C(6) and C(5)–C(6)–S(7) for 1-HC are strongly extended (143.6°), and the bond angle strain on the olefin sp2 carbons was estimated to be 13.7 kcal molµ1 based on 1,2-bis- (methylsulfanyl)ethene as a model.This value is 9.9 kcal molµ1 larger than the corresponding bond angle strains for 1-T. The remaining energy for 1-C is attributed to the repulsion of the sulfur atom lone pairs. Geometries were optimized using the Hartree–Fock (HF) method with double-zeta plus polarization basis set. Energies were obtained using the second-order Møller–Plesset perturbation (MP2) method with the same basis set. The HF-optimized geometries were applied to these energy calculations.This work was supported by Grant-in-Aid for Scientific Research on Priority Areas and General Scientific Research from the Ministry of Educations, Science and Culture, Japan. Technique used: ab initio molecular orbital calculations References: 12 Fig. 2: Correlation diagram between the energies and torsional angles for dimethyl disulfide 5 Table 1: Selected bond lengths, angles, interatomic distances and torsional angles for optimized geometries of 1, 2 and 3 Table 3: Estimated strain energies depending on torsional angles around the olefin moiety and disulfide units Received, 29th July 1996; Accepted, 29th October 1996 Paper E/6/05304A References cited in this synopsis 2 R.Pauncz and D. Ginsburg, Tetrahedron, 1960, 9, 40; N. L. Allinger and J. T. Sprague, J. Am. Chem. Soc., 1972, 94, 5734; Tetrahedron, 1975, 31, 21; O. Ermer, J. Am. Chem. Soc., 1976, 98, 3964; D. N. J. White and M. J. Bovill, J. Chem. Soc., Perkin Trans. 1, 1977, 1610; W. R. Roth, O. Adamczak, R. Breuckmann, H.-W. Lennartz and R. Boese, Chem. Ber., 1991, 124, 2499. 3 T. Shimizu, K. Iwata, N. Kamigata and S. Ikuta, J. Chem. Res. (S), 1994, 436. 7 T. Shimizu, K. Iwata and N. Kamigata, Angew. Chem., 1996, 108, 2505; Angew. Chem., Int. Ed. Engl., 1996, 35, 2357. J. CHEM. RESEARCH (S), 1996 39 Table 1 Relative energies for optimized geometries of (Z,Z)-1, (E,Z)-2 and (E,E)-3 and cycloocta- 1,5-dienes Z,Z E,E E,Z T C HC TB T TC C 25.3b 23.2 14.0 11.8 11.4 5.3 0 a Relative energies --------------------------------------------------------------------------------------------------- (kcal molµ1) 28.2 20.1 12.0 4.2b 2.8 2.0 0 a Relative energies -------------------------------------------------------------------------------------------------------- (kcal molµ1) aGeometry could not be optimized as a stationary point. bTransition stat

ISSN:0308-2342    

DOI:10.1039/a605304a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 40–41 J. Chem. Research (M), 1997, 0336–0343 Synthesis of Novel Spiro and Fused Cyclopenta[c]-pyrazole and -pyrimidine Derivatives Hassan A. Albar,* Mohammed S. I. Makki and Hassan M. Faidallah Department of Chemistry, University of King Abdulaziz, Jeddah 21413, Saudi Arabia Condensation of diarylmethylidenecyclopentanes with hydrazine, hydroxylamine and thiourea derivatives afford the corresponding fused pyrazoles, oxazoles and pyrimidines. Nitrile imides are well known 1,3-dipoles and their reactions with a,b-unsaturated carbonyl compounds,1–4 4-arylmethylideneoxazolones5,6 and 3-arylmethylidene lactones7 have been extensively investigated.On the other hand, it has been reported that 2-substituted 5-methylidenecyclopentan- 2-ones are useful as intermediates for the synthesis of cyclopentenoid antibiotics and anticancer agents.8 For these reasons some new fused cyclopentapyrazole, cyclopentapyrimidine and spiropyrazoline derivatives have been synthesized either by the 1,3-dipolar addition of nitrile imides to arylmethylidenecyclopenta[c]pyrazole derivatives 2–6 or by other methods, with the two-fold objective of preparing compounds of biological importance and studying the regiochemistry of the cycloaddition process.The condensation of substituted hydrazines with the diarylmethylidenecyclopentanones 1a,b afforded 2,3-disubstituted 6-arylmethylidenecyclopenta[1,2-c]pyrazoles 2–6. Mild oxidation of 2, 3 and 5 with bromine water gave the corresponding pyrazoles 7, 8 and 9 respectively.Condensations of hydroxylamine with a,b-unsaturated ketones usually yield the corresponding isoxazolines, but in some cases the product was found to be the isoxazole derivative.9 However, in our case the reactions of 1a,b with hydroxylamine yielded the corresponding isoxazole derivatives 10a,b (Scheme 1). In view of the usefulness of 2-sulfanyl-1,4-dihydropyrimidines as vulcanizing accelerator agents and photographic stabilizers,10 we prepared some new pyrimidine derivatives 11 and 12 from the condensation of 1a with thiourea and methylthiourea.The reaction of 11 with bromoesters afforded the thioesters 13 and 14, while reaction with hydrazine hydrate afforded the 2-hydrazino derivative 15 which on condensation with acetylacetone in refluxing ethanol gave the triazolo derivative 16 (Scheme 1). The reactions of the nitrile imides 17, generated in situ by treatment of the corresponding hydrazonoyl chlorides 18 with triethylamine, with arylmethylidenecyclopentanes 2 and 4c were carried out in refluxing toluene.TLC analysis of the reaction mixture on silica gel with a mixture of light petroleum and ethyl acetate (5 :1 v/v) as eluent showed the formation of only one product. This was confirmed by 1H NMR analysis of the crude reaction product, in which only one methine singlet signal was observed. These findings indicate that the reactions studied are regiospecific, yielding one of the two possible regioisomers 19 and 19p.Techniques used: 1H NMR, MS, IR, elemental analysis References: 12 Table 1: Physical and elemental analytical data for pyrazoline and pyrazole derivatives Table 2: 1H NMR spectral data for the prepared compounds 40 J. CHEM. RESEARCH (S), 1997 Scheme 1 Reagents: i, NH2OH; ii, RNHNH2; iii, Br[CH2]nCO2Et; iv, (CH3CO)2CH2 Scheme 2 *To receive any correspondence.Received, 16th February 1996; Accepted, 29th October 1996 Paper E/6/01146b References cited in this synopsis 1 G.Bianchi, R. Gandolfi and C. DeMicheli, J. Chem. Res., 1981, (S) 6; (M) 0135. 2 S. T. Ezmirly, A. S. Shawali and A. M. Bukari, Tetrahedron, 1988, 44, 1743. 3 A. S. Shawali, B. E. Elanadouli and H. A. Albar, Tetrahedron, 1985, 41, 1877. 4 H. A. Albar, J. Chem. Res., 1996, (S) 316; (M) 1756. 5 N. G. Argypoulos and E. C. Argyropoulou, J. Heterocycl. Chem., 1984, 21, 1397. 6 E. C. Argyropoulou, N. G. Argypoulos and E. Thessalonikeos, J. Chem. Res., 1990, (S) 202; (M) 1557. 7 A. S. Shawali, A. M. Farag, M. S. Algharib and H. A. Albar, J. Chem. Res. (S), 1993, 80. 8 Narasaka Koichi, Jpn. Kokai Tokkyo Appt., 91/331,066, 1991 (Chem. Abstr., 1993, 119, 270683m). 9 A. R. Katritzky, Adv. Heterocycl. Chem., 1963, 2, 370. 10 J. Willems and A. Vandenberghe, C. R. Congr. Int. Chim. Ind., 1958, 31, 476 (Chem. Abstr., 1960, 54, 22657). J. CHEM. RESEARCH (S), 1997 41

ISSN:0308-2342    

DOI:10.1039/a601146b

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 42–43 J. Chem. Research (M), 1997, 0401–0429 Stereochemistry and X-ray Crystal Structure of ‘Pyrrole Trimer’: Synthesis of cis-2,5-Di(pyrrol-2-yl)pyrrolidine (cis Pyrrole Trimer) and X-ray Crystal Structure of cis- 1-(4-Methylphenylsulfonyl)-2,5-di(pyrrol-2-yl)pyrrolidine (Monotosyl cis Pyrrole Trimer) Yuekun Zhao, Roy L. Beddoes and John A. Joule* Chemistry Department, The University of Manchester, Manchester M13 9PL, UK Pyrrole reacts with aqueous hydrochloric acid at 0 °C to give a 2 :1 mixture of trans(1) and cis(2) isomers of 2,5-di(pyrrol- 2-yl)pyrrolidine which, by conversion into a mixture of the corresponding monotosyl derivatives then exposure of these to sodium hydroxide under phase-transfer conditions, are converted completely into the tosyl derivative (4) of the cis isomer, from which the tosyl group can be cleaved to produce pure cis ‘pyrrole trimer’.‘Pyrrole trimer’ [2,3-di(pyrrol-2-yl)pyrrolidine], produced in moderate yield by the brief treatment of pyrrole with 20% aqueous hydrochloric acid at 0 °C, was first described in 18881 but its structure was not established until 1957.2 Later it was assigned3 the stereochemistry shown in 1 on the grounds of the isolation of trans-pyrrolidine-2,5-dicarboxylic acid from oxidative degradation,4 though this work has never been described in full.Requiring the cis isomer 2, we sought confirmation of the trans stereochemistry assigned to pyrrole trimer thinking that it would be necesary to bring about isomerisation.Careful TLC and 1H NMR (in CDCl3) analyses seemed to show that ‘pyrrole trimer’ was homogeneous; however a small crystalline sample was subjected to X-ray analysis from which it was clear (Fig. 1) that the unit cell contained three molecules, two trans, but one cis. Careful HPLC then confirmed the composition of the material and allowed separation of small quantites of the two pure stereoisomers. The mixture of isomers reacted with toluene-p-sulfonyl chloride in the presence of diisopropylethylamine giving a 2:1 mixture of mono-tosyl derivatives, 3 and 4, in which only the central, pyrrolidine nitrogen had reacted.When the mixture of monotosyl derivatives was treated with sodium hydroxide under phase-transfer conditions, quantitative conversion into the pure cis isomer 4 took place. We envisage this as an equilibration, occurring via reversible pyrrole- N·H deprotonation then C·NTs cleavage (Scheme 1).An X-ray crystal-structure determination (Fig. 2) on 4 showed that the two pyrrole rings on one side of the pyrrolidine are well away from the tosyl substituent on the opposite side providing an explanation for the thermodynamic preference for the cis isomer. To conclude the synthesis of pure cis pyrrole trimer 2, sodium–ammonia treatment cleanly and quantitatively converted 4 into 2. 42 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence (e-mail: j.a.joule@man.ac.uk).Fig. 1 ORTEP plot of the structure of ‘pyrrole trimer’, 1+2 Scheme 1 Fig. 2 ORTEP plot of the structure of the monotosyl cis pyrrole trimer 4X-ray Crystallography.·Measurements were made on a Rigaku AFC5R diffractometer with graphite-monochromated MoKa radiation. Data were collected at 19�1 °C. Structures were solved by direct6 (1+2) and heavy-atom Patterson7 methods and expanded using Fourier techniques.8 For 1+2, non-hydrogen atoms were refined anisotropically; for 4, some were refined anisotropically and others isotropically.Hydrogen atoms were included but not refined. Data for 1+2.·Crystal size 0.60Å0.13Å0.13 mm; 5992 unique (Rint=0.021) reflections in the 6389 collected. An empirical absorption correction, using the program DIFABS,9 was applied resulting in transmission factors from 0.80 to 1.00. The data were corrected for Lorentz and polarization effects. A correction for secondary extinction was applied (coefficient=0.13510Å10µ4).The final cycle of fullmatrix least-squares refinement was based on 2397 observed reflections [Ia3.00s(I)] and 406 variable parameters and converged (largest parameter shift was s0.01 times its esd) with unweighted and weighted agreement factors of R=0.089 and Rw=0.064. The standard deviation of an observation of unit weight was 3.31. The weighting scheme was based on counting statistics and included a factor (p=0.005) to downweight the intense reflections.Crystal data for 1+2. Clear, prismatic, primitive monoclinic, Mr 603.81; V=3272(1) Å3; a=9.226(3), b=18.901(3), c=18.786(3) Å, b=92.67(2)°; space group P21/n (No. 14); Z=4; Dcalc=1.23 g cmµ3; F(000)=1296; h, 1 to 10; k, 0 to 22; l, µ22 to 22. Data for 4.·Crystal size 0.13Å0.28Å0.48 mm; 1826 reflections were collected. The data were corrected for Lorentz and polarization effects. The final cycle of full-matrix least-squares refinement was based on 1044 observed reflections [Ia3.00s(I)] and 118 variable parameters and converged (largest parameter shift was s0.01 times its esd) with unweighted and weighted agreement factors of R=0.061 and Rw=0.055.The standard deviation of an observation of unit weight was 3.06. The weighting scheme was based on counting statistics and included a factor (p=0.008) to downweight the intense reflections. The maximum and minimum peaks on the final, difference Fourier map corresponded to 0.33 and µ0.28 e ŵ1, respectively. Crystal data for 4.Clear, prismatic, primitive orthorhombic, Mr 355.45; V=1762.4(6) Å3; a=17.340(4), b=12.302(2), c=8.262(2) Å; space group Pnma (No. 62); Z=4; Dcalc=1.34 g cmµ3; F(000)=752; h, 0 to 20; k, 0 to 14; l, µ9 to 0. Y. Z. is an EPSRC-funded post-doctoral assistant: we thank the EPSRC for their support for this work and the SERC for funds for the purchase of the Rigaku AFC-5R diffractometer. Techniques used: IR, 1H NMR, mass spectrometry, X-ray crystallography References: 9 Schemes: 1 Tables 1–3: For ‘pyrrole trimer’, 1+2: positional parameters and B(eq); intramolecular distances (non-hydrogen atoms); intramolecular bond angles (non-hydrogen atoms) Tables 4–6: For monotosyl cis pyrrole trimer, 4: positional parameters and B(eq); intramolecular distances (non-hydrogen atoms); intramolecular bond angles (non-hydrogen atoms) Appendix: Anisotropic displacement parameters for 1+2 and 4 Received, 19th August 1996; Accepted, 30th October 1996 Paper E/6/05759D References cited in this synopsis 1 M.Dennstedt and J. Zimmerman, Chem. Ber., 1988, 21, 1478. 2 H. A. Potts and G. F. Smith, J. Chem. Soc., 1957, 4018. 3 G. F. Smith, Adv. Heterocycl. Chem., 1963, 2, 287. 4 Personal communication from R. Huisgen and V. Vossius, quoted in ref. 3. 6 R. Miller, S. M. Gallo, H. G. Khalak and C. M. Weeks, J. Appl. Crystallogr., 1994, 27, 613. 7 F. Hai-Fu, Structure analysis programs with intelligent control, Rigaku Corporation, Tokyo, Japan, 1991. 8 DIRDIF94: P. T. Beurskens, G. Admiraal, G. Beurskenes, W. P. Bosman, R. de Gelder, R. Israel and J. M. M. Smits, Technical report of the crystallography laboratory, University of Nijmegen, The Netherlands, 1994. 9 N. Walker and D. Stuart, Acta Crystallogr., Sect. A, 1983, 158. J. CHEM. RESEARCH (S), 1996

ISSN:0308-2342    

DOI:10.1039/a605759d

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 44–45 J. Chem. Research (M), 1997, 0375–0384 Synthesis of Some Coumarin Derivatives as Potential Laser Dyes Mohamed H. Elnagdi,a Sanaa O. Abdallah,*a Khadiga M. Ghoneim,b Elzeni M. Ebiedc and Kawser N. Kassabd aChemistry Department Faculty of Science, Cairo University, Egypt bChemistry Department Faculty of Pharmacy, Cairo University, Egypt cChemistry Department Faculty of Science, Tanta University, Egypt dNational Institute of Laser Science, Cairo University, Egypt With a view to extend the tunability range and maximum output of the coumarin series of dyes, 15 new 3-substituted 7-hydroxycoumarins emitting in the blue-green region of the visible spectrum are synthesized, some of which show laser activity.Several 3-substituted 7-hydroxycoumarins rank among the most efficient photostable laser dyes emitting in the bluegreen region of the visible spectrum. The lasing range covered by coumarin dyes is appreciably extended when the 3-substituent is a heterocyclic moiety.1,2 Therefore it seemed relevant to design and synthesize 7-hydroxycoumarins bearing different heterocycles at the 3-position with the aim to obtain a new photostable laser dyes having rigid structures that are tunable over a wide wavelength range within the visible spectrum.This approach was also stimulated by the assumption that the introduction of biologically active heterocycles at the 3-position of 7-hydroxycoumarin may lead to physiologically active fluorescent compounds of general and analytical biological interest.The syntheses of the new 3-substituted 7-hydroxycoumarins from b-resorcylaldehyde (2,4-dihydroxybenzaldehyde; 1) are outlined in the Scheme. The 3-benzothiazolyl, 3-benzimidazolyl and 3-benzoxazolyl derivatives of 7-hydroxycoumarin 3a–c were synthesized via condensation of b-resorcylaldehyde (1) with benzothiazol- 2-ylacetonitrile (2a),3 1H-benzimidazol-2-ylacetonitrile (2b)4 and benzoxazol-2-ylacetonitrile (2c),5 respectively.Solutions of these 7-hydroxycoumarins in different organic solvents were found to be strongly fluorescent. In order to investigate the effect of introducing an acetoxy group at position 7 on the fluorescence properties of these compounds, the 3-(benzazol-2-yl)-7-acetoxycoumarins 3d–f were prepared by acetylating compounds 3a–c. The strongly fluorescent 3-thiazolyl-7-hydroxycoumarins 6a–c were obtained by the reaction of 1 with 4-aryl-2-cyanomethyl- 1,3-thiazoles 5a–c. 2-Cyanomethyl-4-phenyl-1,3-thiazole (5a)6 was obtained by the reaction of w-bromoacetophenone (4a) with cyanothioacetamide. Likewise, the same method was adopted for the preparation of the novel 2-cyanomethyl-4-p-tolyl-1,3-thiazole (5b) and 4-p-chloro- 44 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence. Schemephenyl-2-cyanomethyl-1,3-thiazole (5c), using w-bromo- 4-methylacetophenone (4b) and w-bromo-4-chloroacetophenone (4c), respectively.Condensing 1 with ethyl (5-aryl-1,3,4-oxadiazol-2-yl)acetate 8a–b in ethanol containing piperidine as a catalyst afforded the 3-(5-aryl-1,3,4-oxadiazol-2-yl)-7-hydroxycoumarins 9a–b. Compound 8a7 was obtained by the reaction of ethyl 3-ethoxy-3-iminopropanoate hydrochloride with benzoylhydrazine (7a). The same method was used to prepare the unreported ethyl (5-p-anisyl-1,3,4-oxadiazol-2-yl)acetate (8b) utilising p-anisoylhydrazine (7b). Many dicoumarins show intensive anticoagulant activity and are used in the therapy of thromboembolisms.Hence it seemed worth synthesizing the dicoumarin 11, which was accomplished by condensing 1 with ethyl (5-cyanomethyl- 1,3,4-oxadiazol-2-yl)acetate (10)8 in a 2 :1 molar ratio in ethanol in presence of piperidine as a catalyst. The preparation of the 3-thiadiazolyl-7-hydroxycoumarins 14a–c was achieved by reacting 1 with the appropriate 2-acylamino- 5-cyanomethyl-1,3,4-thiadiazoles 13a–c. The thiadiazoles 13a9 and 13b10 were synthesized by treating 2-cyanoacetohydrazide with acetyl isothiocyanate (12a) and benzoyl isothiocyanate (12b), respectively.The novel 2-p-anisoylamino-5-cyanomethyl-1,3,4-thiadiazole (13c) was prepared in a similar manner using p-anisoyl isothiocyanate (12c). With a view to standardize the parameters to make the present dyes effective in the field of lasers, a study of their electronic absorption emission and excitation spectra in different organic solvents was carried out.The effects of acidity and temperature as well as dye concentration on their optical properties were also explored. The fluorescence quantum yields (ff) of these dyes are high and some showed lasing activity upon pumping with an N2 laser. The newly synthesized compounds showed variable antibacterial activities against some Gram positive, Gram negative and acid fast bacteria. Only the thiazole and the thiadiazole derivatives 3a, 6a–c and 14a–c showed significant activity against the acid fast Mycobacterium phlei, probably due to their ability to penetrate the lipid-rich cell wall which is resistant to acids, alkalis and chemical disinfectants.However, all compounds showed no significant activity against Pseudomonas fluorescence which is resistant to most antimicrobial agents. Techniques used: 1H NMR, IR, UV–VIS, MS References: 10 Scheme: 1 Received, 29th May 1996; Accepted, 5th October 1996 Paper E/6/03731C References cited in this synopsis 1 K. H. Drexhage, Topics in Applied Physics, Springer-Verlag, New York, 1973, vol. 1. 2 G. Jones II, W. R. Jackson, C. Choi and W. R. Bergmark, J. Phys. Chem., 1985, 89, 294. 3 K. Saito, S. Kambe, Y. Nakano, A. Sakurai and H. Midowkawa, Synthesis, 1983, 210. 4 J. Sawlewicz and B. Milczarska, Pol. J. Pharmacol. Pharm., 1974, 26, 639. 5 H. Moeller and C. Gloxhuber, Ger. Offen., 2 327 959 (Cl. CO 7D, A 6lK), 1975; Appl. Pat., 23 27 959.6-44, 1973 (Chem. Abstr., 1975, 82, 170 876a). 6 V. H. Schafer and K. Gewald, J. Prakt. Chem., 1974, 316, 684. 7 M. H. Elnagdi, A. W. Erian, K. U. Sadek and M. A. Selim, J. Chem. Res. (S), 1990, 148. 8 M. H. Elngadi, N. S. Ibrahiem, F. M. Abdelrazeck and A. W. Erian, Liebigs Ann. Chem., 1988, 909. 9 M. R. H. Elmoghayer, E. A. Ghali, M. M. M. Ramiz and M. H. Elnagdi, Liebigs Ann. Chem., 1985, 1962. 10 M. R. H. Elmoghayer, S. O. Abdallah and M. Y. A. S. Nasr, J. Heterocycl. Chem., 1984, 21, 781. J. CHEM. RESEARCH (S), 1996 45

ISSN:0308-2342    

DOI:10.1039/a603731c

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 46–47 J. Chem. Research (M), 1997, 0430–0436 Triphenyltruxenene: a C48 Polycyclic Buckybowl Precursor M. John Plater,* Marapaka Praveen and Alan R. Howie Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, UK The synthesis and X-ray crystal structure of the title compound are reported. The discovery of the fullerenes has led to a renaissance of interest in the synthesis of strained non-planar fragments whose structures represent sections of the buckminsterfullerene surface.1 Most notable is the synthesis by Rabideau of the C30 fragment semibuckminsterfullerene or hemifullerene by the pyrolysis of a mixture of tri- and tetra-chlorotruxenenes 1.2 This key fragment represents half of the C60 surface and has the correct carbocyclic framework for two enantiomeric halves to dimerise into the C60 cage.3 A previous attempt to prepare hemifullerene by the pyrolysis of truxenene 2 proved unsuccessful.4 Truxenene derivatives and their chemistry are clearly of great interest as a route to ‘buckybowl’ precursors.With this in mind we have prepared triphenyltruxenene 6 and obtained an X-ray crystal structure. Truxenequinone 4 was prepared (see Scheme) by the acidcatalysed cyclotrimerisation of indane-1,3-dione 3.4 Addition of benzylmagnesium bromide to truxenequinone 4 gave a mixture of the two isomeric alcohols 5 which were readily dehydrated to give triphenyltruxenene 6 by treatment with toluene-p-sulfonic acid in refluxing benzene.In contrast to the poor stability of truxenene 2 and the difficulty in preparing it owing to the reactive exocyclic methylene groups,4 triphenyltruxenene 6 is a thermally stable crystalline solid. Owing to the successful pyrolytic synthesis of hemifullerene from 1 by three consecutive ring couplings, the X-ray crystal structure of compound 6 was of particular interest to determine the distances between the coupling sites and to determine the preferred ground-state geometry.Truxenenes can exist in two diastereoisomeric conformations with the lowestenergy conformer calculated to have the three exocyclic alkenes projecting on the same face.4 For truxenene 2 the conformer with two alkenes projecting on one face and the other on the opposite side was calculated at the ab initio 3-21G level to be 2.52 kcal molµ1 less stable. The perspective drawing of the X-ray crystal structure (Figure) shows the molecules to possess a three-fold symmetry axis perpendicular to the best plane of the central six-membered ring.Each alkene group projects onto the same face, as expected from the calculations for truxenene 2,4 and the alkene bond C(9)·C(10) makes a dihedral angle of 22° to the bond C(2ii)·C(1) of the central benzene ring [C(2ii) ·C(1) ·C(9)·C(10)]. The carbon atoms of the ring-coupling position C(4)·C(10i) are fairly close at 3.221(15) Å. Interestingly, the central benzene ring A displays a regular alternation in the bond lengths with C(1)·C(2), C(1i) ·C(2), C(1)i)·(C2i) and (C1ii)·C(2ii) all 1.418(6) Å and C(1)·C(2ii), C(1)i)·C(2) and C(1ii)·C(2i) all 1.387(6) Å.We are currently continuing our studies into the synthesis of halogenated polycyclic derivatives of triphenyltruxenene 6 which may serve as useful precursors to the hemifullerene core. Crystal Data for 6.·C48H30, Mr=606, F(000)=1908, rhombohedral, a=17.457(5), c=19.134(6) Å, V=5050 Å3, space group R3c, (No. 161), Z=6, Dx=1.197 g cmµ3, m(MoKa)=0.063 mmµ1. The experimental data were collected at room temperature on a Nicolet P3 diffractometer using a graphite monochromator with MoKa radiation 46 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence (e-mail: m.j.plater@abdn.ac.uk). Scheme Reagents, conditions and yields: i, conc. H2SO4, room temp., 24 h, 75%; ii, PhCH2MgBr, THF, room temp., 8 h, 99%; iii, TsOH, C6H6, heat, 2 h, 56% Figure Perspective drawing of triphenyltruxenene showing the crystallographic atom-numbering scheme and 40% probability thermal vibration ellipsoids(l=0.71069 Å).The structure was solved by direct methods.5 The final R value was 0.062 (Rw=0.043). The estimated standard deviations for the geometrical parameters involving non-hydrogen atoms lie within the following ranges: bond lengths 0.006–0.015 Å; bond angles 0.6–1.0°. This work was supported by the Enginering and Physical Sciences Research Council (EPSRC) of the United Kingdom. Techniques used: IR, 1H and 13C NMR, mass spectrometry, X-ray crystallography References: 9 Schemes: 1 Table 1: Atomic coordinates and Ueq values for non-hydrogen atoms Table 2: Interatomic distances and angles Received, 14th October 1996; Accepted, 1st November 1996 Paper E/6/06989D References cited in this synopsis 1 P. W. Rabideau and A. Sygula, Acc. Chem. Res., 1996, 29, 235. 2 A. H. Abdourazak, Z. Marcinow, A. Sygula, R. Sygula and P. W. Rabideau, J. Am. Chem. Soc., 1995, 117, 6410. 3 M. J. Plater, H. S. Rzepa and S. Stossel, J. Chem. Soc., Chem. Commun., 1994, 1567. 4 F. Fabris, O. De Lucchi and F. Sbrogio, Synlett., 1994, 761. 5 G. M. Sheldrick, Acta Crystallogr., Sect. A, 1990, 46, 467. J. CHEM. RESEARCH (S), 1996 47

ISSN:0308-2342    

DOI:10.1039/a606989d

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 48–49 J. Chem. Research (M), 1997, 0437–0452 Conformational Analysis of Spirocyclopropane- and Spirooxirane-annelated Dibenzobicyclo[4.4.1]undecanes by 1H NMR Spectroscopy and X-Ray Crystallography Shuntaro Mataka,*a Masahiko Taniguchi,b Yoshiharu Mitroma,b Tsuyoshi Sawadaa and Masahi Tashiroa aInstitute of Advanced Material Study, Kyushu University, 6-1, Kasuga-koh-en, Kasuga-shi, Fukuoka 816, Japan bDepartment of Molecular Science and Technology, Graduate School of Engineering Sciences, Kyushu University, 6-1, Kasuga-koh-en, Kasuga-shi, Fukuoka 816, Japan Conformational behaviour of dibenzo[c,h]bicyclo[4.4.1]undecanes having a dichloro- and a dibromo-cyclopropane ring, together with an oxirane ring on the methylene bridge, has been studied by 1H NMR spectroscopy and X-ray crystallography.Of the possible conformations of bicyclo[4.4.1]undecane, the twin-boat type usually is the most unstable and the twin-chair the most stable.The twin-chair conformer is unstable in the case of dibenzobicyclo[4.4.1]undecane 1, owing to electronic repulsion between the p-electrons of the two layered benzounit, and thus 1 exists as an equilibrium mixture of the chairboat and boat-chair conformers.1 A twin-chair conformation with layered benzo-units is seen in the acetal and the alcohol 2 (Scheme 1),4,5 which have substituents on the methylene bridge of a dibenzobicyclo[4.4.1]undecane system. The present article reports on the conformational behaviour of dibenzobicyclo[4.4.1]undecanes having a spiroannelated three-membered ring on the methylene bridge.The methylene derivative 3 was prepared by dehydration of the alcohol 2 and converted into the spirocyclopropanes 4 and 5 by [2+1] cycloaddition with dihalocarbenes.6,7 Reductive removal of the halogen substituents of 4 with LiAlH4 8 gave 6. In contrast, the dichloro derivative 5 gave a mixture of 6 and the monochloro derivative 7. The desired 6 was more conveniently prepared by a Simmons–Smith reaction.9 Oxirane 8 was obtained by epoxygenation10 with m-chloroperbenzoic acid (m-CPBA) (Scheme 2).The flexible 6 exists at room temperature as an equilibrium of a mixture of the two indistinguishable chair-boat (C-B) and boat-chair (B-C) conformers. In the 1H NMR spectrum of 6 at µ60 °C, one of the two methylene groups of the spirocyclopropane moiety shows an up-field shift, since the methylene protons are shielded by the ring current of the benzene ring of the boat-like benzocycloheptene unit. Introduction of halogen atoms does not fix the conformation of 4, 5 or 7, while oxirane 8 is also flexible (Scheme 3).The conformer ratios for 4, 5 and 8 are given in Table 1. The ratio of 7 could not be determined because of overlapping of the signals. The parameters DH°, DS°, and DG° for 4, 5 and 8 were determined from the signals for the methylene protons of the spirocyclopropane rings and the oxirane ring in variable temperature 1H NMR spectra in CDCl3 run over a temperature range from µ60 to 0 °C (Fig. 1 and Table 2). The predominant conformation of 4 and 5 in solution is the C-B type, although it could be expected that the C-B conformation, in which the dihalogenomethylene group is positioned above the boat-like benzocycloheptene ring, might be sterically less preferable. On the other hand, 4 takes the B-C conformation in the solid state, as revealed by X-ray crystallographic analysis (Fig. 2). The conformer ratio of 5 is dependent on the ET-30 value of the solvent. With an increase in ET-30, the proportion of C-B conformer tends to increase. The solvent effect is less clear in 4. These facts seem to be in agreement with PM3 calculations of the dipole moment: the calculated dipole 48 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence (e-mail: mataka@cm.kyushu-u. ac.jp). Scheme 1 Scheme 2 Scheme 3J. CHEM. RESEARCH (S), 1996 49 Fig. 1 van’t Hoff plot for 4, 5 and 8 Fig. 2 ORTEP drawing of 4 Table 1 Conformer ratiosa and calculated dipole moments of 4, 5 and 8 Ratio of B-C/C-B conformers in solvent (ET-30) Dipole momentb [2H6]Acetone CD2Cl2 CDCl3 [2H8]THF [2H8]Toluene Compd. (B-C/C-B) (42.2) (41.1) (39.1) (37.4) (33.9) 458 1.21 D/1.35 D 1.07 D/1.61 D 1.38 D/2.06 D 40/60 28/72 90/10 37/63 29/71 71/29 37/63 31/69 68/32 47/53 40/60 100/0 43/57 43/57 100/0 aAt µ60 °C. bPM 3 calculation. Table 2 Parameters DH°, DS° and DG° for the B-C and C-B equilibriaa,b Compd.DH° (kJ molµ1) DS° (J molµ1 Kµ1) DG° (kJ molµ1)c 458 3.49 5.15 4.91 11.9 17.4 28.6 µ0.06 µ0.04 µ3.61 aIn CDCl3. bK\[B-C]/[C-B]. cAt 25 °C. moment of the C-B conformer is larger than that of the B-C conformer and the difference between the values is larger in 5 than in 4. The oxirane 8 prefers the B-C conformation in order to avoid the electronic repulsion between the lone-pair electrons of the oxygen atom and the p-electrons of the benzene ring.The ratio for 8 is more temperature-dependent than those for 4 or 5 (Fig. 1); it is estimated that in chloroform at 25 °C, more than 99% of 8 exists as the B-C conformer, having a smaller calculated dipole moment. The large difference in DS° for 8 may reflect tight solvation on the oxygen atom in the B-C conformer as compared to the C-B conformer. Crystal Data for 4.·C21H20Br2, Mr=432.19, orthorhombic, a=24.926(6), b=17.125(1), c=8.253(2) Å, V=3522.9(12) Å3, Dc=1.630 g cmµ3, space group Pbca, Z=8, F(000)=1728, m(CuKa)=5.791 cmµ1.Data were collected on an Enraf Nonius CAD-4 diffractometer using a graphite monochromator with CuKa radiation (l=1.54184 Å). The structure was solved by direct methods (SIR 92).11 The final R value was 0.033 (Rw=0.0886). The estimated standard deviations for the geometrical parameters involving non-hydrogen atoms lie within the following ranges: bond lengths, 0.004– 0.006 Å; bond angles 0.2–0.4°. We are indebted to Dr T.Thiemann (University of Coimbra) for helpful discussions. Techniques used: IR, 1H NMR, mass spectrometry References: 11 Schemes: 3 Figures: 2 Tables 3–6: Bond lengths and angles, fractional atomic coordinates and equivalent isotropic thermal parameters, and anisotropic thermal parameters for 4 Received, 15th July 1996; Accepted, 5th November 1996 Paper E/6/04939G References 1 S. Mataka, K. Takahashi, T. Hirota, K. Takuma, H. Kobayashi, M. Tashiro, K. Imada and M. Kuniyoshi, J. Org. Chem., 1986, 51, 4618. 4 S. Mataka, K. Takahashi, T. Hirota, K. Takuma, H. Kobayashi and M. Tashiro, J. Chem. Soc., Chem. Commun., 1985, 973. 5 S. Mataka, K. Takahashi, T. Hirota, K. Takuma, H. Kobayashi, M. Tashiro, K. Imada and M. Kuniyoshi, J. Org. Chem., 1985, 52, 2653. 6 G. W. Gokel, J. P. Shepherd, W. P. Weber, H. G. Boettger, J. L. Holwick and D. J. McAdoo, J. Org. Chem., 1973, 38, 1913. 7 L. A. Last, E. R. Fretz and R. M. Coates, J. Org. Chem., 1982, 47, 3211. 8 C. W. Jefford, D. Kirkpatrick and F. Delay, J. Am. Chem. Soc., 1972, 94, 8905. 9 R. J. Rawson and I. T. Harrison, J. Org. Chem., 1970, 35, 2057. 10 L. V. Hijfe, R. D. Little, J. Petersen and K. D. Moeller, J. Org. Chem., 1987, 52, 4647. 11 M. C. Altomare, M. Burla, G. Camalli, C. Cascarano, A. Giacovazzo, G. Guagliardi and J. Polidori, J. Appl. Crystallogr., 1994, 27, 435.

ISSN:0308-2342    

DOI:10.1039/a604939g

出版商:RSC    

年代:1997

数据来源: RSC