摘要:

OEt O O N O O HN OEt N O O R3 N N O R1 R2 R3 HO N O OH N N R1 R2 OEt aq. HCl, reflux O R1 R2 R1 = R2 = H, Cl R1R2 = [CH]4 R3 = H cis or trans isomer R1 = R2 = H, Cl R1R2 = [CH]4 R3 = H trans isomer dry EtOH dry HCl room temp. dry EtOH dry HCl room temp. cis isomer R1 = R2 = R3 = H aq. HCl, reflux R1 = R2 = H R3 = Me, Ph cis or trans isomer R3 = H aq. HCl reflux H2/Pd 3 2 1 4 34–78% 50–80% N N O HO Ph CH2Ph N O CH2Ph Ph OH OEt O N N CH2Ph Ph OEt O C Ph NHCH2Ph H O N O CH2Ph Ph O + dry HCl dry EtOH room temp.aq. HCl reflux 8 7 6 5 J. CHEM. RESEARCH (S), 1997 115 J. Chem. Research (S), 1997, 115 J. Chem. Research (M), 1997, 0701–0719 The Reactions of w-Hydroxylactams obtained from the Photocyclisation of Dicarboximide Mannich Bases: a Route to Substituted Imidazoles Marjory Close,a John D. Coyle,*b Edmund J. Hawsa and Christopher J. Perrya aSchool of Applied Sciences, The University of Wolverhampton, Wolverhampton, West Midlands WV1 1SB, UK bCookson Group plc, 130 Wood Street, London EC2V 6EQ, UK Substituted imidazoles are formed by treatment of w-hydroxylactams with anhydrous ethanolic HCl.Although there have been many reports on the photocyclisation of N-substituted imides to give w-hydroxylactams,1 there have been few on the chemistry of these products. We have previously shown that lactams obtained from aromatic dicarboximide Mannich bases are converted by aqueous acid into quinolizinones or isoquinolinones.4e,5 We have now obtained further evidence for the mechanism of this reaction and also report that under anhydrous conditions a different reaction occurs to give a substituted imidazole.This reaction appears to have widespread application. We have shown that both cis and trans isomers of lactam 1 can be converted into quinolizinone 2 on heating with aqueous HCl and that this reaction proceeds via a dione which can be isolated when the labile H is replaced by a Me or a Ph group. Under anhydrous conditions the isomers behave differently; the trans isomer and its dichloro and naphthyl analogues are converted at room temperature into substituted imidazoles 3; a similar reaction occurs with the hydroxylactam derived from succinimide.Treatment of the cis isomer of 1 under the same conditions or the trans isomer with ethanolic HCl containing 10–50% water gave the iminoketoester 4 in addition to the imidazole. Hydrogenation of 4 followed by treatment with aqueous acid gave 2. Lactam 5 with anhydrous acid gave a mixture of imidazole 6 and an aminoketoester 7 the latter spontaneously changing via a dione to the isoquinolinone 8. Techniques used: IR, 1H and 13C NMR, MS References: 21 Schemes: 4 Received, 24th October 1996; Accepted, 16th December 1996 Paper E/6/07266F References cited in this synopsis 1 (a) Y. Kanaoka, Acc. Chem. Res., 1978, 11, 407 and references cited therein.; (b) J. D. Coyle, Pure Appl. Chem., 1988, 60, 941 and references cited therein. 4 (e) J. D. Coyle, J. F. Challiner, E. J. Haws and G. L. Newport, J. Chem. Res., 1985, (S) 351; (M) 3748. 5 J. D. Coyle, J. F. Challiner, E. J. Haws and G. L. Newport, J. Heterocycl. Chem., 1980, 1131. *To receive any correspondence. Scheme 1 Scheme 2

ISSN:0308-2342    

DOI:10.1039/a607266f

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

O O O O O O O OO 1 2 3 O 116 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 116–117 J. Chem. Research (M), 1997, 0720–0724 Synthesis of Acenaphthenequinone Bis(ethylene ketal): an Unusually Distorted Ketal M. John Plater,* Derek M. Schmidt and R. Alan Howie Department of Chemistry, Aberdeen University, Meston Walk, Aberdeen AB24 3UE, UK The title compound is prepared by the acid catalysed protection of acenaphthenequinone with ethylene glycol and characterised by single crystal X-ray crystallography.In the course of our synthetic studies aimed at the regiospecific functionalisation of polycyclic aromatic hydrocarbons for the synthesis of fragments of the buckminsterfullerene surface,1 we required a protected derivative of acenaphthenequinone. The two electrophilic carbonyl groups were expected to form ketals readily under acid catalysis and not undergo a benzil–benzilic acid ring contraction as this would lead to the formation of a strained fourmembered 1,1-peri-fused naphthalene.It was of interest to see which of the two possible ketals 2 or 3 would predominate as a consequence of molecular strain, anomeric effects and electrostatic repulsion between the electronegative oxygens. Treatment of acenaphthenequinone 1 with ethylene glycol and a catalytic amount of toluene-p-sulfonic acid in refluxing benzene with azeotropic removal of water gave a single colourless crystalline product in 70% yield. The IR spectrum showed the absence of a carbonyl group and the mass spectrum confirmed the molecular structure as the bis ketal 2 or 3.The 13C NMR spectrum confirmed the presence of a single product and showed one sharp resonance for the ethylene bridge carbons. The 1H NMR spectrum was, however, complex and difficult to interpret. A single-crystal X-ray structure determination confirmed ketal 3 to be the correct structure. The molecule adopts a cistetraoxadecalin double chair conformation with C2 symmetry (see Figure).This product is probably thermodynamically more stable than the alternative isomer 2 because the oxygens adopt a pairwise axial–equatorial arrangement which will reduce their electrostatic repulsion compared to the eclipsed oxygens in isomer 2. The complex 1H NMR spectrum is probably a well resolved AApBBp spectrum, owing to a rapid double chair inversion, to which we were unable to assign coupling constants. The spectrum is complex because each pair of chemically equivalent protons on the ethylene bridge (AAp and BBp) has a different J value (JAB8JABp) so that they are magnetically non-equivalent.2 Variable temperature 1H NMR spectroscopy confirmed the molecular flexibility because on heating to 110 °C in deuterated toluene the methylene proton spectrum remained sharp and unchanged, but on cooling between µ36 and µ40 °C the spectrum changed from a 16 to an 8 line spectrum.The geometry of six-membered rings allows for more favourable stabilising ground state anomeric effects than the geometry of five-membered rings.However, although the crystal structure shows some disorder limiting the accuracy to which the bond lengths can be determined, the C–O bond lengths are not consistent for a stabilising anomeric effect. The bonds C(1)–O(1) are in a pseudoaxial position relative to the C(1)–O(2) bonds of the adjacent ring and hence a stabilising anomeric effect would have been expected to lengthen the C(1)–O(1) bond and shorten the C(1)–O(2) bond.3–5 In the crystal structure the opposite variation of bond lengths is observed with the C(1)–O(1) bond (1.315 Å) considerably shorter than the C(1)–O(2) bond (1.488 Å).The expected anomeric effect appears to have been dominated by the influence of the planar p-system. The C(1)–O(1) bond lies approximately in the plane of the aromatic ring, and hence perpendicular to the p-system, while the C(1)–O(2) bond is remarkably close to 90° to the aromatic ring and coplanar with the p-system [(C(2)–C(1)–O(2)i=93.9° and C(1)i–C(1)–O(2)i=102.0°)].The long C(1)–O(2) bond could therefore be explained as a consequence of a ground state stereoelectronic effect owing to the electron push from the aromatic ring. Crystal data for 3. C16H14O4, Mr=170, F(000)=5680, monoclinic, a=11.561(11), b=8.768(5), c=13.092(9) Å, V=1247.6(16) Å3, space group C2/c (no. 15), Z=4, Dr=1.439 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 (l=0.71069 Å).The structure was solved by direct methods.6 The final R value was 0.058 (Rw=0.060). The estimated standard deviations for the geometrical parameters involving non-hydrogen atoms lie within the following ranges: bond lengths 0.006–0.021 Å; bond angles 0.3–1.8°. Techniques used: IR, 1H and 13C NMR, X-ray crystallography References: 11 Tables: 2 (atomic coordinates and Ueq values for non-H atoms; interatomic distances and angles) *To receive any correspondence. Figure Crystal structure of 3J. CHEM. RESEARCH (S), 1997 117 Received, 31st October 1996; Accepted, 19th December 1996 Paper E/6/07414F References cited in this synopsis 1 M. J. Plater, M. Praveen and D. M. Schmidt, Fullerene Science and Technology, in press. 2 W. Kemp, NMR in Chemistry: A Multinuclear Introduction, Mac- Millan, London, 1992. 3 P. Deslongchamps, Stereoelectronic Effects in Organic Chemistry, Pergamon Press, Oxford, 1986. 4 B. Fuchs, I. Goldberg and U. Schmueli, J. Chem. Soc., Perkin Trans. 2, 1972, 357. 5 L. Lopez, V. Cal`o and F. Stasi, Synthesis, 1987, 947. 6 G. M. Sheldrick, Acta Crystallogr., Sect. A, 1990, 46, 467.

ISSN:0308-2342    

DOI:10.1039/a607414f

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

PhthN O Cl PMP N Me N R PMP N PhthN N R PMP O PMP Me H N H2N OH R O PMP Me H H PhthN O Cl PMP N H OCH2Ph Me N PhthN OCH2Ph Me O PMP H H N H2N OH Me O PMP H H H three CH2Cl2 R = H R = Me 4 R = H R = Me H H N O PMP steps Et3N + 4 N O PMP 5 175 R = H R = Me ac O O 8 two steps N O PMP Et3N CH2Cl2 + 8b O O 207 14 15 ZNH (CO2Et)2 22 25 two steps steps three Me2 Me2 N S H3N HN O N O CO2H O SO3 – R2 O2 CNH2 H H R1 + 1 2 3 4 1¢ R1 = R2 = H R1 = Me, R2 = H R1 = H, R2 = Me R1 = R2 = Me R1 = CH2O2CNH2, R2 = H 1 a b c d 2 Carumonan 1, 2a–d† 118 J.CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 118–119 J. Chem. Research (M), 1997, 0725–0748 Simple and Condensed b-Lactams. Part 28.1 The Synthesis of C-Methylcarumonams and of a Related Bis(carbamate) J�ozsef Fetter,*a Ferenc Bertha,a M�aria Kajt�ar-Peredy,b K�aroly Lemperta and Attila S�apia aDepartment of Organic Chemistry, Technical University Budapest, H-1521 Budapest, Hungary bCentral Research Institute for Chemistry of the Hungarian Academy of Sciences, H-1525 Budapest, Hungary Racemic carumonam analogues 2a–d are synthesised and found to be devoid of any bacterial activity; NaBH4 reduction of 18 affords both epimers of 8c with the (3RS,4RS)-4-[(1RS)] epimer as the main product, and cyclocondensation of phthalimidoacetyl chloride with racemic imine 14 gives rise to the formation of (3RS,4RS)-4-[(1RS)]-15 as a single epimer.In the course of our studies into structure–activity relationships in the carumonam 12 series we have synthesised racemic C-substituted derivatives 2a–d of carumonam via key intermediates 8a–c and 25, respectively, as outlined in the Scheme. The two epimers of compound 8c were obtained by sodium tetrahydroborate reduction of acetyl derivative 185 (resulting from imine 175 on acid hydrolysis), followed by N-deacylation.As shown by X-ray molecular structure determination,13 the (3RS,4RS)-4-[(1RS)] epimer of compound 8c was formed as the main product. This is in agreement with the Felkin– Anh model14,15 of nucleophilic additions to the carbonyl group.On the other hand, cyclocondensation of phthalimidoacetyl chloride with racemic imine 14 afforded, in agreement with our expectation, the (3RS,4RS)-4-[(1RS)] compound 15 as the only epimer. Compounds 8a–c were subsequently converted by benzyloxycarbonylation into compounds 26a–c, while treatment of compound 25 with cation exchange resin Varion KS/H+ afforded compound 26d.Compounds 26a–d were converted in five steps (successive treatment with chlorosulfonyl isocyanate and aqueous NaSO3; demethoxyphenylation with CAN;8 N-sulfonation with pyridiniosulfonate, ion pair extraction9 and treatment with cation exchange resin Varion KS/Na+; debenzyloxycarbonylation by catalytic hydrogenolysis; acylation with acylating agent 3310 and de-tert-butylation) into the corresponding compounds 2a–d, none of which exhibited antibacterial activities. Techniques used: column chromatography, TLC, IR, 1H and 13C NMR, NOE, elemental analysis References: 15 Schemes: 7 *To receive any correspondence. †Compounds 2a–d are racemic, only one enantiomer shown; 2b,c have 2 epimers each.Scheme Synthesis of key intermediates 8a–c and 25. PhthN=phthalimido, PMP=4-methoxyphenyl, Z=benzyloxycarbonyl. Compounds 5, 8a–c, 14, 15 and 17 are racemic; only one enantiomer is shown. Both epimers of compound 8c have been isolated.N PhthN O Me PMP O H Me N H2N OH Me PMP O H Me H N ZNH OH R2 PMP O H Me N S N O S S N O CO2But a Racemic compounds, only one enantiomer shown. b (3 RS,4 RS)-4-[(1 RS)] epimer.c Both epimers. 18 a (3 RS,4 RS)-4-[(1 RS)]-8c a 26 3310 Me H Me CH2OH H Meb Mec H R1 H R2 H2N a b c d J. CHEM. RESEARCH (S), 1997 119 Received, 27th November 1996; Accepted, 23rd December 1996 Paper E/6/08035I References cited in this synopsis 1 Part 27, Le Thanh Giang, J. Fetter, K. Lempert, M. Kajt�ar- Peredy and A. G�om�ory, Tetrahedron, 1996, 52, 10 169. 2 M. Sendai, S. Hashiguchi, M. Tomimoto, S. Kishimoto, T. Matsuo, M. Kondo and M. Ochiai, J. Antibiot., 1985, 38, 346. 5 J. Fetter, H. V�as�arhelyi, M. Kajt�ar-Peredy, K. Lempert, J. Tam�as and G. Czira, Tetrahedron, 1995, 51, 4763. 8 D. R. Kronenthal, C. Y. Han and M. K. Taylor, J. Org. Chem., 1982, 47, 2765. 9 C. M. Cimarusti, H. E. Applegate, H. W. Chang, D. M. Floyd, W. H. Koster, W. A. Slusarchyk and M. G. Young, J. Org. Chem., 1982, 47, 179. 10 Takeda Chemical Industries, Eur. Pat. Appl., EP 93.376, 1983 (Chem. Abstr., 1984, 100, P 209.515z). 13 A. K�alm�an, personal communication. 14 M. Cerest, H. Felkin and N. Prudent, Tetrahedron Lett., 1968, 2199. 15 N. T. Anh and O. Eisenstein, Nouv. J. Chim., 1977, 1, 61; N. T. Anh, Top.

ISSN:0308-2342    

DOI:10.1039/a608035i

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

R Q X HO HO OH O O 1 3 6 5 1 3 6 5 1 3 6 5 1 C O 3 6 OH 5 1 3 6 5 9 13 15 15¢ 13¢ 9¢ a b c d e 1 Zeaxanthin (R = Q = a, X = OH) 3 Capsorubin (R = Q = e) 5 Lutein epoxide (R = b, Q = d) 2 Violaxanthin (R = Q = b) 4 Capsanthin (R = a, X = OH, Q = e) 120 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 120–121 J. Chem. Research (M), 1997, 0801–0841 Kinetic Studies on the Thermal Z/E-Isomerization of C40-Carotenoids P�eter Moln�ar,*a Tam�as K�ortv�elyesi,b Zolt�an Matusa and J�ozsef Szabolcs† Department of Medical Chemistry, University Medical School of P�ecs, Szigeti �ut 12., H-7624 P�ecs, Hungary bInstitute of Physical Chemistry, J�ozsef Attila University, Szeged Rerrich B.t�er 1., H-6720 Szeged, Hungary The kinetics of thermal Z/E-isomerization among all-E-, 9(9p)Z-, 13(13p)Z- and 15Z-isomers of zeaxanthin 1, violaxanthin 2, capsorubin 3, capsanthin 4 and lutein epoxide 5 are studied at 333.4–368.4 K. The thermal isomerization of 1–5 in pyridine or benzene over the temperature range 333–368 K yielded complex equilibria25 –26 governed by first-order forward and reverse elementary steps.28–29 In compliance with the analytical approach, four models (I–IV) were used to describe the mechanisms by which the Z- and all-E-isomers were interconverted.Model I was used to describe the thermal Z/E-isomerization when the formation or the consumption of the Z-isomers with high cis-peaks (13Z, 13pZ and 15Z) was monitored by UV–VIS-spectrophotometry:1,22,25–26,28–30 k1 All-EM13[13p(15)]Z kµ1 Model II consists of two reversible concurrent reactions11,23,25,32 and is represented by the following systems, typical of a symmetrical carotenoid: kµ1 k2 13ZMAll-EM15Z k1 kµ2 and an unsymmetrical carotenoid. kµ1 k2 13ZMAll-EM13pZ k1 kµ2 The reactions leading to equilibria were followed by HPLC.Model III was used for more complex systems containing All-E-, 13Z-, 15Z-, 9Z- and di-Z-isomers:22 kµ1 k2 13ZMAll-EM15Z k1 kµ2 kµ3 k3 9Z+di-Z (mixed peak) For the evaluation of the rate constants the respective formation and consumption of the 9Z-and di-Z- isomers were considered together.Model IV was based on the most detailed analysis of the thermal isomerization mixtures. *To receive any correspondence (e-mail: molpeter@apacs. pote.hu). †Present address: Benc�es Gimn�azium, V�ar 1., H-9090 Pannonhalma, Hungary. Table 7 Arrhenius and activation parameters of the reversible isomerization of the (all-E)-1 to (13Z)-1 and (15Z)-1 using the rate constants obtained in the simulation of the reaction mechanism defined by models II and III; Tav.=357.4 Ka Rate constant log (A/sµ1) EA/kJ molµ1 DH‡/kJ molµ1 DS‡/J molµ1 Kµ1 DG‡/kJ molµ1 Model II k1 kµ1 k2 kµ2 11.53 (0.31) 10.68 (0.16) 12.85 (0.41) 13.39 (0.61) 104.6 (3.1) 97.0 (1.3) 118.6 (4.6) 115.6 (11.1) 101.6 (3.1) 94.0 (1.4) 116.9 (5.1) 112.6 (11.2) µ34.1 µ50.6 µ5.1 µ1.6 113.8 112.1 118.7 112.0 Model III k1 kµ1 k2 kµ2 k3 kµ3 11.55 (0.48) 10.60 (0.26) 12.77 (0.42) 13.22 (0.67) —— 104.9 (6.0) 96.6 (2.4) 118.0 (4.8) 114.5 (10.8) —— 102.0 (6.0) 93.6 (2.4) 115.1 (4.8) 111.6 (10.8) —— µ33.6 µ51.8 µ10.3 µ1.8 —— 114.0 112.1 118.8 118.2 —— aData in parentheses are the standard deviations.Arrhenius and activation parameters of reactions (3), (µ3) and (4), (µ4) are not given because of significant error. Model IV was used, with relatively high deviation, to calculate k3, kµ3 and K4 MJ. CHEM.RESEARCH (S), 1997 121 kµ1 k2 13ZMAll-EM15Z k1 kµ2 kµ3 k3 9Z kµ4 k4 di-Z (mixed peak) Rate constants were calculated using the program package ZITA for advanced kinetic simulations;24 that is, the ordinary differential equations (ODE) of the kinetic models were solved by the GEAR method.33 Curve fitting was carried out applying the Marquard–Levenberg method.34 The Arrhenius parameters were calculated by non-linear parameter estimation with statistical weights wi=1/k2i . Values of EA, DH‡, DS‡, DG‡ and A were obtained from the rate constants determined on the basis of Models I–IV.The Arrhenius and activation parameters for thermal interconversions among (all-E)-1, (13Z)-1 and (15Z)-1, calculated from the rate constants obtained in simulation of the different models (II–IV), are listed in Table 7. Techniques used: UV–VIS spectroscopy, HPLC, column chromatography References: 48 Tables: 12 Received, 18th November 1996; Accepted, 23rd December 1996 Paper E/6/07820F References cited in this synopsis 1 J.Szabolcs, Pure Appl. Chem., 1976, 47, 147. 11 C. A. Pesek, J. J. Warthesen and P. S. Taoukis, J. Agric. Food Chem., 1990, 38, 41. 22 B. H. Chen, T. M. Chen and J. T. Chien, J. Agric. Food Chem., 1994, 421, 2391. 23 W. von E. Doering, C. Sotiriou-Leventis and W. R. Roth, J. Am. Chem. Soc., 1995, 117, 2747. 24 G. Peintler, A Comprehensive Program Package for Fitting Parameters of Chemical Reaction Mechanisms, A. J. University, Szeged (Hungary), 1993. 25 P.Moln�ar, Structural Elucidation of Mono- and Di-cis-Carotenoids, Isolation of New Carotenoids, Kinetics of E/Z-Isomerization, Ph.D. Dissertation, Department of Medical Chemistry, University Medical School of P�ecs, Hungary, 1988. 26 L. Zechmeister, Cis-Trans Isomeric Carotenoids, Vitamins A and Arylpolyenes, Springer, Wien, 1962. 28 Z. G. Szab�o, in Comprehensive Chemical Kinetics, ed C. H. Bamford and C. F. H. Tipper, Elsevier, Amsterdam, 1969, vol. 2, ch. 1. 29 K. Schwetlick, Reakci�omechanizmusok kinetikai viszg�alata (Investigation of Kinetics and Mechanism of Reactions), Mu��szaki K�onyvkiad �o (Technological Publishing House), Budapest, 1978. 30 H. A. Franck, Ann. N.Y. Acad. Sci., 1993, 691, 1. 32 (a) G. N. Vriens, Ind. Eng. Chem., 1954, 669l; (b) N. A. Sørensen, Beitr�age zur Kinetik der Mutarotation, I Kommission Hos F. Bruns Bokhandel, Trondheim, 1937. 33 A. C. Hindmarsch, Ordinary Differential Equation Solver, UCID- 30001 rev. 3. Lawrence Livermore Laboratory, P.O. Box 808, Livermore, CA 94550, 1974. 34 Y. Bard, Nonlinear Paramet

ISSN:0308-2342    

DOI:10.1039/a607820f

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

124 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 124–125 J. Chem. Research (M), 1997, 0773–0794 Rapid Synthesis of (�)-(E)- and (�)-(Z)-1-Amino- 1-aminomethyl-2-(hydroxymethyl)cyclopropanes, Preparation of their Dichloroplatinum(II) Complexes, and Crystal Structure of a Derivative of the (�)-(E) Isomer Fabrice Vergne,a David J. Aitken,*a Ang`ele Chiaroni,b Claude Richeb and Henri-Philippe Hussona aLaboratoire de Chimie Th�erapeutique associ�e au CNRS, Facult�e des Sciences Pharmaceutiques et Biologiques, Universit�e Ren�e Descartes (Paris V), 4 Avenue de l’Observatoire, 75270 Paris cedex 06, France bLaboratoire de Cristallochimie, Institut de Chimie des Substances Naturelles du CNRS, Avenue de la Terrasse, 99198 Gif-sur-Yvette cedex, France An efficient four-step synthesis of racemic Z and E forms of 1-amino-1-aminomethyl-2-(hydroxymethyl)cyclopropane is described, along with the preparation and cell-growth inhibition evaluation of the corresponding dichloroplatinum(II) complexes; the crystal structure of the synthetic intermediate (E)-1-[(benzyloxycarbonyl)aminomethyl]-1-dibenzylamino- 2-(hydroxymethyl)cyclopropane has been determined. Cyclopropane compounds continue to attract interest on account of their varied chemical and biological properties.1,2 As part of our research programme dealing with the preparation of polyfunctional cyclopropanes, particularly those containing diamine functions,15,26 we were interested in the synthesis of both diastereoisomers of the trifunctional molecule (�) - 1 - amino - 1 - aminomethyl - 2 - (hydroxymethyl)cyclopropane 2.In the search for new analogues of the anticancer drug cisplatin,16,17 the dichloroplatinum(II) complexes of 2 appeared attractive targets, since the presence of a peripheral non-metal-bound hydroxy group might be expected to improve the aqueous solubility and induce different biological activity profiles.23,24 The title compounds were prepared conveniently as shown in the Scheme.Double alkylation of N,N-dibenzylaminoacetonitrile with epibromohydrin gave cyclopropane 510 as a mixture of diastereoisomers (60 : 40), which was reduced with an excesss of borane.THF to give the diamine 6. It is noteworthy that no other products, such as those that might conceivably arise from decyanation25 or rearrangement processes, 26 were observed. Treatment of 6 with benzyl *To receive any correspondence. Scheme Fig. 1 X-Ray structure of compound (E)-7J. CHEM. RESEARCH (S), 1997 125 chloroformate led to the carbamate 7 whose low polarity facilitated separation of Z and E diastereoisomeric forms by flash chromatography. Each isomer of 7 was completely deprotected by hydrogenolysis to give the title compounds as hygroscopic oils. Each of the four steps in this sequence proceeded in high yield. Surprisingly, several attempts to transform the hydroxy group of (Z)-7 or (E)-7 into a halide or phosphate ester function met with failure, although it was possible to obtain the corresponding acetates by reaction with acetic anhydride.There was no obvious reason for the unusual lack of reactivity of the primary alcohol, but it was interesting to observe the existence of an intramolecular hydrogen bond between the carbamate hydrogen atom and the hydroxy group oxygen atom in the crystal structure of (E)-7 (Fig. 1), a phenomenon which could conceivably diminish the reactivity of the alcohol function.The dichloroplatinum(II) complexes 9 and 10 were prepared by reaction of the appropriate isomer of 2 with potassium tetrachloroplatinate. The expected cis-N2Cl2 squareplanar platinum ligand set was confirmed by the 195Pt NMR resonances at around µ2200 ppm,27 thus confirming that the hydroxy function was not metal-bound. The in vitro cellgrowth inhibition activities of 9 and 10 were evaluated as IC50 values on L1210 (murine leukaemia) cells, and were found to be 32 mM and a50 mM respectively. Both compounds were thus at least an order of magnitude less potent than cisplatin (IC50=1.6 mM).Crystal Data for (E)-7.·C27H30N2O3, Mr=430.55, orthorhombic, space group Pbca, Z=8, a=8.383(6), b=13.146(9), c=44.094(20) Å, V=4859.3 Å3, dc=1.18 g cmµ3, F(000)=1840, l(CuKa)=1.5418 Å, m=0.57 mmµ1. Experimental data were collected on a Nonius CAD-4 diffractometer using graphite-monochromated CuKa radiation. The structure was solved by direct methods and the final R value was 0.065 (Rw=0.079).Estimated standard deviations for geometrical parameters involving non-hydrogen atoms lie within the following ranges: bond lengths, 0.007–0.021 Å; bond angles, 0.4–1.3°. We thank Dr F. Libot (CNRS URA 1310) for recording mass spectra and Dr F. Siret (CNRS URA 400) for recording 195Pt NMR spectra. We are grateful to the Experimental Cancerology Laboratory of Institut de Recherches Servier for carrying out the biological tests, to the Comptoir Lyon Alemand Louyot for the gift of potassium tetrachloroplatinate, and to the Ligue Nationale Contre le Cancer for a fellowship to F.V.References: 30 Schemes: 2 Tables 1–5: Fractional atomic coordinates for non-H atoms, fractional atomic coordinates for H atoms, anisotropic thermal parameters, bond lengths and angles and selected torsion angles Received, 7th October 1996; Accepted, 2nd January 1997 Paper E/6/06840E References cited in this synopsis 1 The Chemistry of the Cyclopropyl Group, ed.Z. Rappoport, Wiley, New York, 1987. 2 J. Sala�un and M. S. Baird, Curr. Med. Chem., 1995, 2, 545; C. J. Suckling, Angew. Chem., Int. Ed. Engl., 1988, 27, 537. 10 D. Guillaume, D. J. Aitken and H.-P. Husson, Synlett, 1991, 747; D. J. Aitken, F. Vergne, A. S. Phimmanao, D. Guillaume and H.-P. Husson, Synlett, 1993, 599. 15 F. Vergne, D. J. Aitken and H.-P. Husson, J. Org. Chem., 1992, 57, 6071. 16 Platinum and Other Metal Complexes in Cancer Chemotherapy, ed. M. Nicolini, Martinus Nijhoff, Boston, 1988. 17 N. Farrell, Transition Metal Complexes as Drugs and Chemotherapeutic Agents, Kluwer Academic Press, Dordrecht, 1989. 23 S. Hanessian and J. Wang, Can. J. Chem., 1993, 71, 2102. 24 P. Mailliet, E. Segal-Bendirdjian, J. Kozelka, M. Barreau, B. Baudoin, M.-C. Bissery, S. Gontier, A. Laoui, F. Lavelle, J. B. Le Pecq and J.-C. Chottard, Anti-Cancer Drug Design, 1995, 10, 51. 25 K. Ogura, Y. Shimamura and M. Fujita, J. Org. Chem., 1991, 56, 2920. 26 F. Vergne, K. Partogyan, D. J. Aitken and H.-P. Husson, Tetrahedron, 1996, 52, 2421. 27 P. S. Pregosin, Annu. Rep. NMR Spectr

ISSN:0308-2342    

DOI:10.1039/a606840e

出版商:RSC    

年代:1997

数据来源: RSC

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126 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 126–127 J. Chem. Research (M), 1997, 0842–0849 Interaction of (+)-Tartrate with Methanediol in Alkaline Solutions Eugenijus Norkus,*a Algirdas Va8skelis,a Eugenijus Butkusb and Rasa Pauliukaitÿea aInstitute of Chemistry, A. Go8stauto 9, 2600 Vilnius, Lithuania bDepartment of Organic Chemistry, Vilnius University, Naugarduko 24, 2060 Vilnius, Lithuania The equilibrium of acetal-type compound formation from (+)-tartrate and methanediol in alkaline solutions has been studied and characterized quantitatively.The ability of formaldehyde to oxidize on Hg has been detected recently and (+)-tartrate [(2R,3R)-tartrate] has been shown to have a retarding effect on the oxidation process. 4 Mixed CuII complexes with tartrate and formaldehyde have been shown to form in some cases.5 Formaldehyde is known to exist largely in hydrated form in solution (Ke=2A103):6 HCHO+H2OmH2C(OH)2 (1) The dissociation of methanediol takes place in alkaline soltuions (pKa1137): H2C(OH)2mH2C(OH)Oµ+H+ (2) The limiting current of methanediol oxidation on a dropping mercury electrode (DME) is diffusion limited.The values of ilim do not depend on solution pH in the range 13.2–13.7 (0.1–0.6 mol dmµ3 NaOH) (curve 1, Fig. 2). The decrease in ilim in more alkaline solutions (pHa13.7) is related to increase in solution viscosity. The addition of tartrate into alkaline methanediol solutions at pH 13.0–14.0 diminishes the ilim (curve 2, Fig. 2). The results obtained can be explained by binding of a part of the methanediol to an electrochemically non-active compound which does not take part in the anodic oxidation process. On the basis of polarographic data a reaction for the formation of an acetal-type compound from methanediol and tartrate anion is proposed: COOµ COOµ ! ! HC·OH HC·O ! +H2 C(OH)2m ! \ /CH2+2H2O (3) HC·OH HC·O ! ! COOµ COOµ Ke The equilibrium constant Ke of reaction (3) was calculated from polarographic data (values of ilim), assuming that ilim is proportional to the methanediol concentration in solution and that equilibrium (3) is rather slow (acetal does not dissociate additionally in the polarographic oxidation process).The dissociation of one tartrate anion OHµ group was taken in account (pKa3=14.38): C4O6H4 2µ(T2µ)mC4O6H3 3µ(T3µ)+H+ (4) The results obtained show good agreement between the calculated log Ke values over the total pH range investigated, with the equilibrium of reaction (3) being shifted to the left (log Ke=µ0.810.1).The results obtained were confirmed using 1H NMR techniques. The 1H NMR spectra of formaldehyde in a D2O solution were recorded over the pH range 10–14. At pH 10, in addition to the solvent signal, the NMR spectrum exhibits a single signal for the methylene protons of the hydrated form of formaldehyde at d 4.88. At pH 14 a single peak is observed at d 4.90. The chemical shift difference between these two lines is small, ca.d 0.02, as should be expected since the magnetic environments of methanediol and its anion are very similar. The spectra observed may be explained by the dissociation reaction (2) and a weighted average of the two forms of methanediol is detected by NMR. Intensity measurements are inaccurate because the signals fall on the side of the strong water signal. The 1H NMR spectrum of the tartrate solution in D2O shows a single peak at d 4.35 for the protons adjacent to the hydroxy groups over the range of pH values studied.The mixtures of the solutions discussed above using various molar ratios of the compounds, i.e. tartrate–CH2O 10:1, 1:1 and 1: 2, were studied over the pH range 10–14, the NMR spectra being recorded at appropriate time intervals. The 1H NMR spectra recorded within a few minutes after making up of the solutions displayed signals corresponding to the individual components of the mixture with the shift values discussed above.However, after a 10–20 min period (this corresponds to the procedure used for polarographic measurements) new signals at d 5.16 and 4.62 could be detected. The shape of the signals indicates an interaction between the tartrate and the methanediol, resulting in the formation of the symmetrical structure as shown in eqn. (3). The singlet at d 5.16 is about 10% of the intensity of the methylene signal of methanediol and was assigned to the formation of an acetal-type compound [eqn.(3)]. The signal for the methylene protons is displaced downfield compared to that for hydrated acetals,9 and this can be explained by the non-customary acetal structure of this compound. This signal is observed also after the mixture was kept at room tempera- *To receive any correspondence (e-mail: vaskelis@ktl.mii.lt). Fig. 2 Dependence of the limiting current of methanediol oxidation on a DME on the solution pH: solution composition: 1, 3.2 mmol dmµ3 methanediol+NaOH; 2, 3.2 mmol dmµ3 methanediol+40 mmol dmµ3 (+)-tartrate+NaOHJ. CHEM.RESEARCH (S), 1997 127 ture for several days, although the intensity of the methylene signal of methanediol decreases significantly over this period owing to the Cannizzaro reaction. Peaks at d 3.35 and 8.46 are observed after 30 min of mixing the solutions and correspond to the methyl group of methanol and the methylene proton of formate ion, respectively. These signals increase significantly after longer reaction periods and ultimately the methylene signal of the methanediol is of the same intensity as the proton signal of the formate ion.We thank Mrs Marija Krenevi8cienÿe for assistance with the NMR experiments. Techniques used: DC-polarography, 1H NMR References: 9 Fig. 1: Polarographic calibration graph Fig. 3: 1H NMR spectrum of (+)-tartrate–methanediol mixture at pH 13 after 20 min Fig. 4: 1H NMR spectrum of (+)-tartrate–methanediol mixture at pH 13 after 12 h Table 1: Equilibria concentrations of reacting species and calculated values of log Ke of reaction (3) Received, 5th August 1996; Accepted, 2nd January 1997 Paper E/6/05461G References cited in this synopsis 4 A. Va8skelis and E. Norkus, J. Electroanal. Chem., 1991, 318, 373. 5 A. Va8skelis, E. Norkus and I. 8Zakaitÿe, Galvanotechnik in press. 6 L. F. Roeleveld, J. M. Los and B. J. C. Wetsema, J. Electroanal. Chem., 1975, 75, 819. 7 R. Schumacher, J. J. Pesek and O. R. Melroy, J. Phys. Chem., 1985, 89, 4338. 8 E. P. Serjeant and B. Dempsey, Ionisation Constants of Organic Acids in Aqueous Solutions, Pergamon, Oxford, 1979. 9 P. Greenzaid, Z. Luz and D. Samuel, J. Am. Chem. Soc., 1967, 89, 749.

ISSN:0308-2342    

DOI:10.1039/a605461g

出版商:RSC    

年代:1997

数据来源: RSC

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N N Me N OH O Ph N N Me N O OH Ph N N Me N OEt O Ph N N Me Ph O N Me N N Br H Me Ph O N N Me Ph OH Br N N Me Ph N Me OH OH N N Me Ph Cl Br N N Me Ph 1b 1a MeCH2I, K2CO3, –HI N Me 5 OH Cl –H2O, –HI 2 MeCONH2, pyridine, –HBr MeCONH2, pyridine, –HBr –H2O –HCl 4 3b 3a N N O N Me Me Ph N N O N OHC CHO Ph N N O N Ph N N Et Et Me N Et –2 H2O +2 N N O N OHC CHO Ph 7 N N O N Ph 9a-b N Et + N Et + I– H2O + 5 A 6 Me + A = 1-ethylpyridinium-2-yl A = 1-ethylquinolinium-2-yl A = 1-ethylpyridinium-4-yl 8,9a bc +2 SeO2 8a-c +1 SeO2 + 1,4-Dioxane A A 2 I– I– I– + A A Me 128 J.CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 128–129 J. Chem. Research (M), 1997, 0850–0865 Synthesis and Electronic Absorption Spectra of Some Five-membered Bisheterocyclic Polymethine Cyanine Dyes Reda Mahmoud Abd El-Aal Chemistry Department, Aswan-Faculty of Science, Aswan, Egypt 3,5-Dimethyl-1-phenyl-1H-pyrazolo[4,3-d]oxazole 5 was prepared and used as starting material in the synthesis of some new polymethine cyanine dyes incorporating a bisheterocyclic system.Polymethine cyanine dyes1 including mono-, di- and trimethine types have found various applications as photographic sensitisers for both colour and black and white films2 and textile dyes.3 They are also useful as photosensitisers in blue green light4–6 and as analytical reagents.7 In the present paper, a new synthesis of 3,5-dimethyl- 1-phenyl-1H-pyrazolo[4,3-d]oxazole 5 is developed and con- firmed by the interaction between 4-bromo-3-methyl- 1-phenyl-1,4-dihydropyrazol-5-one (3ak3b)8 and/or 4- bromo-5-chloro-3-methyl-1-phenylpyrazole 4 with pyridine as catalyst and ethanol as solvents, Scheme 1.Selective oxidation of 5 with an equi- or bi-molar ratio of SeO2 17 in boiling 1,4-dioxane afforded the corresponding 3 - m e t h y l - 1 - p h e n y l - 1 H- p y r a z o l o [ 4 , 3 - d] o x a z o l e - 5 - c a r b a l d e - hyde 6 or its 3,5-dicarbaldehyde 7, respectively.The 1H NMR spectra of the aldehydes 6 and 7 show characteristic absorptions at d 10.2 and 10.0, respectively, for the CHO groups and other signals which, along with the IR spectra, are presented in Table 4 (full text). The condensation of compounds 6 and 7 with 2(4)-methylsubstituted heterocyclic quaternary salts (equi- or bi-molar) in refluxing ethanol in the presence of piperidine as catalyst afforded the corresponding asymmetric 3-methyl-1-phenyl- 1H-pyrazolo[4,3-d]oxazol-5-yl [2(4)]-dimethine (8a–c) and symmetric 1-phenyl-1H-pyrazolo[4,3-d]oxazole-3,5-diyl [2(4)]- bis(dimethine) cyanine dyes (9a–c), Scheme 3.Quaternisation of 3,5-dimethyl-1-phenyl-1H-pyrazolo[4,3- d]oxazole 5 using iodoethane afforded the corresponding b i s q u a t e r n a r y - 2 , 4 - d i e t h y l - 3 , 5 - d i m e t h y l - 1 - p h e n y l - 1 H- p y r a - zolo[4,3-d]oxazole-2,4-diium bis(iodide) 10. Interaction of 10 with 1-methyl-pyridinium (-quinolinium or -isoquinolinium) iodide (equi- or bi-molar) afforded the corresponding asym- Scheme 1 Scheme 3N N O N Ph Et Et Me N N O N Ph N Et N N O N Ph Me Me N+ N O N Ph Me Me Et Et N Et +2 N Et Et Et N+ N O N Ph N Et Et Et Me N+ N O N Ph Et Et H2C (EtO)2CH CH2 CH(OEt)2 N Et +2 N Et 12a–c + 11,12 N Et + A = 1-ethylpyridinium-4-yl A = 1-ethylquinolinium-4-yl A = 1-ethylisoquinolinium-1-yl N+ N O N Ph Et Et a bc 2 I– A 5 10 + 2 I– A 2 I– + A + + 11a–c + 2 I– 2 I– 14 16a–c N+ N O N Ph A Et Et A Me + CH2CH(OEt)2 +2 CH(OEt)3 N Et + 13 15,16 N Et I– + 15a–c + CH(OEt)3 A = 1-ethylpyridinium-2-yl A = 1-ethylisoquinolinium-2 -yl A = 1-ethylpyridinium-4-yl a bc A EtI Me + A 2 I– A 2 I– + A + A 2 I– N Et + Me 2 I– + J.CHEM. RESEARCH (S), 1997 129 metric and symmetric monomethine cyanines 11a–c and 12a–c, Scheme 4. Treatment of 10 with ethyl orthoformate (equi- or bimolar) in the presence of piperidine afforded compounds 13 and 14 respectively. These compounds are key intermediates in the synthesis of asymmetric and symmetric trimethine cyanine dyes 15a–c and 16a–c via condensation with 2(4)-methyl-substituted heterocyclic quaternary salts (equior bi-molar).The electronic absorption spectra of the asymmetric and symmetric dimethine (8a–c, 9a–c), monomethine (11a–c, 12a–c) and trimethine (15a–c, 16a–c) cyanine dyes in 95% ethanol were dependent on the nature of the heterocyclic quaternary salts (A) and on the type of cyanine molecules, i.e. whether asymmetric or symmetric.The structures of all new compounds were confirmed by elemental analysis as well as by IR and 1H NMR spectral data. I am grateful to Professor Dr A. I. M. Koraiem, Professor of organic chemistry, Aswan-Faculty of Science, for his help and guidance in the preparation of the manuscript. Techniques used: IR, 1H NMR, GCMS, UV–VIS References: 17 Schemes: 4 Table 1: Characterisation data for 6, 7, 8a–c and 9a–c Table 2: Characterisation data for 10, 11a–c and 12a–c Table 3: Characterisation data for 13, 14, 15a–c and 16a–c Table 4: IR and 1H NMR data of selected cyanine dyes Received, 13th June 1996; Accepted, 3rd January 1997 Paper E/6/04155H References cited in this synopsis 1 N.Tyutyuikov, J. Fabian, A. Mehlhorm, F. Dietz and A. Tadjer, Polymethine Dyes – Structure and Properties, St. Kliment Ohridski University Press, Sofia, Bulgaria, 1991. 2 A. M. Osman and Z. H. Kalil, J. Appl. Chem. Biotechnol., 1975, 25, 633. 3 G. D. Kandel and G. F. Duffin, Br. Pat., 797 144, 1930. 4 L. G. S. Brooker and G. H. Keyes, J. Am. Chem. Soc., 1935, 57, 2488. 5 M. S. Fujiravara, T. K. Masukawe and M. Kawasaki, Ger. Offen., 2 734 335, 1978 (Chem. Abstr., 1978, 88, 161 442c). 6 S. Baba, B. Okubo and E. Sakamato, Ger. Offen., 260 968, 1976 (Chem. Abstr., 1977, 86, 49 175a). 7 A. S. Fakhonov, A. A. Anisimova, K. N. Bagdasarov and M. S. Chernovyant, Zh. Anal. Khim., 1984, 39, 1040. 13 L. Smith, Kgl. Fysiograf. Sallskab, Lond., Forh., 18 No. 1, 3, 1948 (Chem. Abstr., 1950, 44, 490. 17 Z. H. Khalil, A. I. M. Koraiem, M. A. El-Maghraby and R. M. Abu El-Hamd, J. Chem. Tech. Biotechnol., 1986, 36, 379. Scheme 4

ISSN:0308-2342    

DOI:10.1039/a604155h

出版商:RSC    

年代:1997

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130 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 130–131 J. Chem. Research (M), 1997, 0879–0866 Novel Reactions of Methyl 4-(Triphenylarsoranylidene)but- 2-enoate and Substituted 2H-Pyran-5-carboxylates: the Preparation of Highly Functionalized trans- 2,3-Divinylcyclopropanecarboxylates Cornelis M. Moorhoff Department of Chemistry, University of Tasmania, GPO Box 252-75, Hobart, Tasmania, Australia 7001 Crotonate arsonium ylide reacted with 2H-pyran-5-carboxylates to give divinylcyclopropanecarboxylates. 2H-Pyran-2-carboxylates 13 have the unique character to undergo reversible electrocyclic ring opening to the ketodiene 2,5 making these compounds available for Michael attack (Scheme 1). In this paper we have investigated novel reactions of substituted 2H-pyran-5-carboxylates 1 and methyl 4-(triphenylarsoranylidene)but-2-enoate 3.7 A Ca–C3 Michael attack of 3 to 2 followed by ring closure and expulsion of triphenylarsine gave mainly highly functionalized trans-2,3-divinylcyclopropanecarboxylates 4 (Scheme 1).Likewise, 2H-pyran-5-carboxylates 1b and 1c gave a mixture of diastereomeric trans-2,3-divinylcyclopropanecarboxylates 4b and 4c. Cyclopropanation from conjugated carbonyl compounds with arsonium ylides is known.14 Vinylcyclopropanation from conjugated carbonyl compounds and arsonium ylides is less common.16 Both trans- and cis-2,3-divinylcyclopropanecarboxylates 4 show large vicinal coupling constants.21 Jvic(trans) was in the range 7.0–7.9 Hz, and Jvic(cis) between 8.6 and 9.3 Hz.Apart from a diastereomeric mixture of cyclopropanes 4c, the reaction of 3 and 1c gave cyclohexa-3,5-diene-1,3-dicarboxylate 6c. A Cg–C3-Michael attack of the g-ylide of 3 on 2c followed by an intramolecular Wittig condensation gave 6c (Scheme 2).2,22 The 2H-pyrans 1d and 1e reacted with 3 and gave, apart from the expected mixture of diastereomeric trans-cyclopropanecarboxylates 4d and 4e, the trans-fused tetrahydrobenzofurans 7d and 7e respectively.This is the result of an initial Cg–C5 Michael addition as illustrated (Scheme 3). Then an intramolecular Ca–C3 nucleophilic attack of the new intermediate arsonium ylide occurs. This is followed by an attack of the enolate oxygen on Ca with the simultaneous expulsion of triphenylarsine to give the tetrahydrobenzofuran 7. The formation of dihydrofuran compounds is rare in arsonium ylide chemistry.25 Techniques used: 1H NMR, 13C NMR, CI HRMS, IR, UV References: 25 Schemes: 6 Received, 14th November 1996; Accepted, 14th January 1997 Paper E/6/07733A Table Products arising from reactions of 2H-pyran-5- carboxylates 1 with methyl 4-(triphenylarsoranylidene)-but-2- enoate 3 2H-Pyran-5-carboxylate Product yields (%) 1 X R Rp 4 6 7 a bc def H Cl HH Cl Br Me Me Me HH Me OMe OMe SEt OMe OMe OMe 71 33 35 47 24 2 3 — 12 2 —— 98 Scheme 1 Scheme 2 Scheme 3J.CHEM. RESEARCH (S), 1997 131 References cited in this synopsis 2 C. M. Moorhoff, Ph.D. Thesis, University of Stellenbosch, 1986. 3 Zh. A. Krasnaya, E. P. Prokof’ev, V. F. Kucherov and M. Sh. Zaripova, Izv. Akad. Nauk. SSSR, Ser. Khim., 1973, 10, 2356 (Chem. Abstr., 1974, 80, 47772v). 5 T. A. Gosink, J. Org. Chem., 1974, 39, 1942. 7 Y.-Z. Huang, Y.-C. Shen, J. Zheng and S. Zhang, Synthesis, 1985, 57. 14 Y.-Z. Huang, Y.-C. Shen, Y.-K. Xin and J.-J. Ma, Sci. Sin. (Engl. Ed.), 1980, 23, 1396. 16 Y. Shen and Y. Xiang, J. Chem. Res. (S), 1994, 198. 21 (a) Y. Tang, Z.-F. Chi, Y.-Z. Huang, L.-X. Dai and Y.-H. Yu, Tetrahedron, 1996, 52, 8747. 22 For the phosphonium analogue, see: F. Bohlmann and C. Zdero, Chem. Ber., 1973, 106, 3779. 25 V. G. Kharitonov, V. A. Nikanorov, S. V. Sergeev, M. V. Galakhov, S. O. Yakushin, V. V. Mikul’shina, V. I. Rozenberg and O. A. Reutov, Dokl. Akad. Nauk SSSR, 1991, 319 (Chem. Abstr., 1992, 116, 83474v).

ISSN:0308-2342    

DOI:10.1039/a607733a

出版商:RSC    

年代:1997

数据来源: RSC

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132 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 132–133 J. Chem. Research (M), 1997, 0880–0894 Synthesis of an Areno-anellated [3.3.1]Propellane Gerald Dyker,*a Jutta K�orning,b Peter Bubenitschekb and Peter G. Jonesc aFachbereich 6, Organische/Metallorganische Chemie der Gerhard-Mercator-Universit�at-GH Duisburg, Lotharstraße 1, D-47048 Duisburg, Germany bInstitut f�ur Organische Chemie der Technischen Universit�at Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany cInstitut f�ur Anorganische Chemie und Analytische Chemie der Technischen Universit�at Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany The reactivity of a highly strained [3.3.1]propellane 6 is exemplified by the addition of formic acid to the central C–C single bond.Propellanes have stimulated a multitude of syntheses and investigations of their chemical and physical properties because of their fascinating topology. Small-ring propellanes are especially of interest with regard to their structure and reactivity, as they allow the study of effects of high ring strain and in some cases inverted carbon geometries.1 Despite steric hindrance, the central C–C single bond of small-ring propellanes is, in practice, an available reaction site. Addition of carboxylic acids is a typical method used to determine the reactivity of these single bonds: the [4.2.1]propellane 1 adds acetic acid with a half life of 1.6 h at 50 °C,2 whereas the [3.3.1]propellane 23 and the [3.2.1]propellane 34 react rapidly at room temperature.The reactivity of other [3.3.1]propellanes5–7 was only examined marginally. Here we report the facile synthesis and structure of an areno-anellated [3.3.1]propellane. We tested two independent pathways to the [3.3.1]propellane 6 starting from the pentalene system 4.8,9 The reaction of 4 with dibromocarbene, generated in situ from tribromomethane and sodium hydroxide by phase-transfer catalysis, led to the formation of a poorly soluble powder in 87% yield, the mass spectrum of which was in accord with cycloadduct 5.The transformation into hydrocarbon 6, and at the same time the chemical proof of structure 5, took place via radical hydrodebromination with tributyltin hydride. The partially dehalogenated compound 7 was isolated as a by-product. Compared to this two-step procedure, the alternative onestep approach to 6 involving a Simmons–Smith reaction10 proved to be superior because it gave a higher overall yield, although in this case the major by-product, the isopropylsubstituted hydrocarbon 8, was formed in a side reaction, since the propellane 6 itself is stable under Simmons–Smith conditions.The mechanism for the formation of 8 is still unknown, but one can speculate that the isopropyl group is presumably formed via a methylene transfer involving C–H insertion into the ethylzinc group. X-Ray crystal structure analysis11 of the small-ring propellane 6 revealed an elongation of the central single bond C-6b–C-12b with a bond length of 155.4(2) pm compared to that in cyclopropane (152 pm). The geometry at the bridgehead carbon atoms is on the verge of being inverted; a slight pyramidalization was still observed: the carbon atom C-6b is only 6.0 pm out of the plane defined by the neighbouring carbon atoms C-6a, C-6c and C-13.Because of the distorted geometry at the bridgehead positions a pronounced reactivity was anticipated.In fact, the propellane 6 reacted slowly with formic acid at 95 °C (24 h reaction time). The formate 9 and the tertiary alcohol 10 were isolated as products of the addition reaction. Obviously, 10 is formed by hydrolysis of 9, as the product ratio is shifted in favour of 10 with increasing reaction time. From this result it is clear that 6 is somewhat less reactive towards the addition of carboxylic acids than the small-ring propellanes 1, 2 and 3. Crystal data for 6.C23H14, triclinic, space group P�1, a=770.38(12), b=881.9(2), c=1147.9(2) pm, a= 101.492(9)°, b=107.875(9)°, g=93.999(11)°, V=0.7201 nm3, Z=2, Dx=1.339 mg mµ3, l(Mo-Ka)=71.073 pm, m=0.08 mmµ1, T=µ130 °C. Data collection and reduction. A colourless tablet 0.8Å0.7Å0.3 mm was mounted in inert oil. Data were collected to 2ymax 50° with a Stoe SDADI-4 diffractometer. Of 2817 measured data, 2549 were unique. Structure solution and refinement. The structure was solved by direct methods and refined anisotropically on F2 by using *To receive any correspondence.Scheme 1J. CHEM. RESEARCH (S), 1997 133 all reflections (program SHELXL-93, G. M. Sheldrick, University of G�ottingen). Hydrogen atoms were included by using a riding model. The final wR(F2) was 0.104 for 209 parameters, conventional R(F) 0.038. S=1.04; max. D/ss0.001; max. D/r=227 e nmµ3. Financial support by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie is gratefully acknowledged. Techniques used: IR, UV–VIS, 1H and 13C NMR, EI-MS, elemental analysis, X-ray analysis Schemes: 1 Tables: 3 Figure: 1 Received, 23rd December 1996; Accepted, 10th January 1997 Paper E/6/08573C References cited in this synopsis 1 K.B. Wiberg, Chem. Rev., 1989, 89, 975. 2 P. Warner and R. LaRose, Tetrahedron Lett., 1972, 21, 2141. 3 R. E. Pincock, J. Schmidt, W. B. Scott and E. J. Torupka, Can. J. Chem., 1972, 50, 3958. 4 K. Wiberg and G. J. Burgmaier, J. Am. Chem. Soc., 1972, 94, 7396. 5 I. D. Reingold and J. Drake, Tetrahedron Lett., 1989, 30, 1921. 6 L. A. Paquette, T. Kobayashi and J. C. Gallucci, J. Am. Chem. Soc., 1988, 110, 1305. 7 A. Schuster and D. Kuck, Angew. Chem., 1991, 103, 1717; Angew. Chem., Int. Ed. Engl., 1991, 30, 1699. 8 G. Dyker, Tetrahedron Lett., 1991, 32, 7241. 9 G. Dyker, J. K�orning, P. G. Jones and P. Bubenitschek, Angew. Chem., 1993, 105, 1805; Angew. Chem., Int. Ed. Engl., 1993, 32, 1733. 10 S. E. Denmark and J. P. Edwards, J. Org. Chem., 1991, 56, 6974. Fig. 1 Molecu

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DOI:10.1039/a608573c

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年代:1997

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134 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 134–135 J. Chem. Research (M), 1997, 0901–0924 Synthesis of New Naturally Occurring 6-Deoxo Brassinosteroids Suguru Takatsuto,*a Tsuyoshi Watanabe,b Shozo Fujiokac and Akira Sakuraic aDepartment of Chemistry, Joetsu University of Education, Joetsu-shi, Niigata 943, Japan bTama Biochemical Co. Ltd., 2-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 163, Japan cThe Institute of Physical and Chemical Research (RIKEN), Wako-shi, Saitama 351-01, Japan New natural 6-deoxo brassinosteroids, 6-deoxoteasterone 1, 3-dehydro-6-deoxoteasterone 2 and 6-deoxotyphasterol 3, as well as 6-deoxocastasterone 4, are synthesized from (20S)-20-formyl-6b-methoxy-3a,5-cyclo-5a-pregnane 5.The occurrence of new 6-deoxo brassinosteroids (BRs), 6-deoxoteasterone 1, 3-dehydro-6-deoxoteasterone 2 and 6-deoxotyphasterol 3, along with 6-deoxocastasterone 4 (Fig. 1) in plants, has been demonstrated.3,4,6 Recently, we have identified 6-deoxotyphasterol 3, 6-deoxocastasterone 4, typhasterol and castasterone in a wild type of Arabidopsis thaliana, suggesting the possibility that both the late and early C6-oxidation pathways4 of the BR biosynthesis are operating in A.thaliana.9 In order to establish the involvement of the late C6-oxidation pathway of the brassinolide biosynthesis in A. thaliana, the 6-deoxo BRs (1, 2, 3 and 4) are required as authentic specimens. It is also necessary to evaluate their biological activities.Because of the scarcity of the natural products, we now describe the synthesis of these 6-deoxo BRs. The side chain of these 6-deoxo BRs was constructed in six steps (Scheme 1) in 26% overall yield from the known C-22-aldehyde 5.12 The key reactions for the construction of the (22R,23R,24S)-side chain of these C28 BRs are the reaction of the C-22-aldehyde 5 with the Grignard reagent derived from (Z)-1-bromoprop-1-ene, orthoester Claisen rearrangement13 of the resulting (22S,23Z)-allylic alcohol, and the asymmetric dihydroxylation10 of the crinosterol side chain.As the transformation of the diol 9 into brassinolide is *To receive any correspondence. Fig. 1 Structure of 6-deoxo brassinosteroids 1–4 Scheme 1 Reagent and conditions: i, BrMgCH�CHCH3, THF, 0 °C to room temp., 1 h; ii, Et(OEt)3, propionic acid, xylene, reflux, 2 h; iii, LiAlH4, THF, reflux, 2 h; iv, MeSO2Cl, Et3N, toluene, room temp., 2 h; v, OsO4, K3[Fe(CN)6], dihydroquinidine p-chlorobenzoate, K2CO3, methanesulfonamide, ButOH–H2O, room temp., 15 d Scheme 2 Reagent and conditions: i, TsOH, aq.dioxane, reflux, 4 h; ii, H2/Pd–C, EtOH, 40 °C, 2 h; iii, TsOH, acetone, room temp., 1 h; iv, MeSO2Cl, pyridine, room temp., 1 h; v, KO2, 18-crown-6, DMSO–DMF, room temp., 2 h; vi, 70% aq. AcOH, 100 °C, 4 h; vii, 5% KOH–MeOH, room temp., 1 h; viii, PCC, CH2Cl2, room temp., 1 h; ix, Li2CO3, DMF, 170 °C, 1 h; x, OsO4, NMO, aq. THF, room temp., 4 hJ. CHEM.RESEARCH (S), 1997 135 known,18 the formal synthesis of brassinolide was achieved. We next modified the A/B ring of the diol 9 for the target 6-deoxo BRs (Scheme 2). Regeneration of a 5-en-3b-ol system followed by hydrogenation provided 6-deoxoteasterone 1 quantitatively, which was converted to the sulfonate 11. Introduction of the 3a-hydroxy and 2-ene functionality was achieved in 66 and 71% yield, respectively. The 3a-alcohol 12 was deprotected to afford 6-deoxotyphasterol 3.The alcohol 12 was oxidized to give, after deprotection, 3-dehydro- 6-deoxoteasterone 2 in 83% yield. Introduction of the 2a,3a-diol group into the 2-ene 14 followed by deprotection afforded 6-deoxocastasterone 4 in 72% yield. In conclusion, we have developed a convenient method to construct the (22R,23R,24S) side chain of natural C28 BRs and synthesized three new 6-deoxo BRs (1, 2 and 3) and also 6-deoxocastasterone 4. The method is also suitable for the preparation of biosynthetically important 6-oxo BRs such as teasterone, 3-dehydroteasterone, typhasterol and castasterone.Techniques used: 1H and 13C NMR, EI-MS, EI-HR-MS, FAB-MS References: 38 Figure: 1 Schemes: 2 Received, 10th December 1996; Accepted, 17th January 1997 Paper E/6/08323D References cited in this synopsis 3 P. G. Griffiths, J. M. Sasse, T. Yokota and D. W. Cameron, Biosci. Biotech. Biochem., 1995, 59, 956. 4 Y.-H. Choi, S. Fujioka, T. Nomura, A. Harada, T. Yokota, S. Takatsuto and A. Sakurai, Phytochemistry, 1997, 44, 609. 6 Y.-H. Choi, S. Fujioka, A. Harada, T. Yokota, S. Takatsuto and A. Sakurai, Phytochemistry, 1996, 43, 593. 9 S. Fujioka, Y.-H. Choi, S. Takatsuto, T. Yokota, J. Li, J. Chory and A. Sakurai, Plant Cell Physiol., 1996, 37, 1201. 10 (c) W. Amberg, Y. L. Bennani, R. K. Chadha, G. A. Crispino, W. D. Davis, J. Hartung, K.-S. Jeong, Y. Ogino, T. Shibata and K. B. Sharpless, J. Org. Chem., 1993, 58, 844. 12 (a) D. G. Anderson, J. P. Thomas, C. Djerassi, J. Fayos and J. Clardy, J. Am. Chem. Soc., 1981, 53, 2307. 13 (a) M. Anastasia, P. Allevi, P. Ciuffreda and A. Fiecchi, J. Chem. Soc., Perkin Trans. 1, 1983, 2365. 18 S. Fung and J. B. Siddall, J. Am. Chem. Soc., 1980, 102, 658

ISSN:0308-2342    

DOI:10.1039/a608323d

出版商:RSC    

年代:1997

数据来源: RSC