摘要:

N N O Me CN PhCH CHCOMe N H X Me H H Ph O MeOC H N H OH Me CONH2 H R O NC H RCH C(CN)CONH2 N H2NOC R CN O Me N H2NOC R CN O Me H 1 3 H 2, EtOH, C5H11N CH3COCH2CONH2 4 X = OH 5 X = OMe O CONH2 NH H 2, EtOH, C5H11N 6 7 N O H2NOC HO Me O NH2 H 2, EtOH, MeCO2NH4 H 2, C5H11N a, R = Ph; b, R = C6H4OMe- o; N H2NOC Me O Me d, e, c, R = C6H4OMe- p; R = C6H4Me- p; f, R = 4-pyridyl N O H2NOC Me O O 8 12 H R = C6H4Me-m; H 2, EtOH, C5H11N 9 H 10 11 13 2, C5H11N 2 J. Chem. Research (S), 1997, 50–51 J.Chem. Research (M), 1997, 0476–0497 Formation of Polysubstituted Pyridin-2-one Derivatives by Michael Addition of 3-Oxobutanamide to a,b-Ethylenic Ketones and Amides Conor N. O’Callaghan,* T. Brian H. McMurry, John E. O’Brien, Sylvia M. Draper and Fiona K. Gormley University Chemical Laboratory, Trinity College, Dublin 2, Ireland Reaction of 3-oxobutanamide with 4-phenylbut-3-en-2-one and with 3-aryl-2-cyanoprop-2-enamides and related compounds affords new di-, tetra- and hexa-hydropyridin-2-one derivatives, the degree of unsaturation of the product depending on the experimental conditions. Pyridin-2-one derivatives are of considerable biological importance, both as cardiotonic agents such as Milrinone 11 and as potential HIV-1 specific reverse transcriptase inhibitors. 2,3 The Michael addition of 3-oxobutanamide 2 to ethylenic ketones C�C·C�O and ethylenic amides C�C·C(�O)NH2, followed by cyclisation, provides a useful synthetic route to these compounds.When 3-oxobutanamide undergoes addition to 4-phenylbut- 3-en-2-one 3, cyclisation takes place through the amide group of the addend, affording the acetyl-substituted piperidin- 2-one derivative 4 (Scheme 1). Recrystallisation from methanol converts this into the methoxy derivative 5, the conformation of which, as determined by X-ray diffraction, is presented in Fig. 1 (where the heterocyclic ring has been numbered in accord with chemical numbering). It is evident that the 3- and 4-protons are axial, as is also the 6-methoxy group. 50 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence. Scheme 1 Fig. 1 Molecular structure of 3-acetyl-6-methoxy-6-methyl- 4-phenylpiperidin-2-one 5, showing the crystallographic numbering system Table Crystallographic data for compound 5 Molecular formula C15H19NO3 Mr 261.31 Crystal system monoclinic Space group p21/a Unit cell dimensions: a/Å b/Å c/Å b/° 11.893(3) 7.4378(8) 17.279(4) 108.877(11) V/A3 Z Dc/g cmµ3 Absorption coefficient/mmµ1 F(000) Crystal size y range Total data measured Total data unique Refinement method Number of parameters Goodness-of-fit on F2 Final R indices [Ia2s(I)] R indices (all data) Largest diff.peak and hole 1446.2(5) 4 1.200 0.083 560 0.45 mmÅ0.45 mmÅ0.35 mm 1.25–21.99° 1879 1769 [R(int)=0.0084] Full-matrix least-squares on F2 248 1.029 R1=0.0524, Rw=0.1266 R1=0.0850, Rw=0.1484 0.198 and µ0.174 e ŵ3In contrast to the reaction which affords the acetyl derivative 4, addition of 3-oxobutanamide to 2-cyanoprop-2-enamides 6 in ethanol containing piperidine results in cyclisation through the acetyl group of the addend, with formation of carbamoyl-substituted piperidin-2-ones 7, the stereochemistry of which is determined by NMR (J values and NOE experiments).(Some carbamoyl derivatives of pyridinones have previously been obtained from the reaction of a,b-unsaturated ketones with malonamide5,6,7 and cyanoacetamide. 8) The degree of saturation of the products obtained from the aryl-substituted amides 6a–e depends on the experimental conditions used.In the presence of ammonium acetate, loss of water occurs during the reaction, which affords tetrahydropyridin-2-ones 8, while in the absence of solvent loss of hydrogen also occurs and 1,2-dihydropyridin- 2-ones 9 are formed. The dipyridyl derivative 9f is readily obtained from 6f under very mild conditions. In a related synthesis, the reaction of 3-oxobutanamide with the bicyclic amide 10 affords the related saturated (11) and unsaturated (13) tricyclic products, together with the dimeric side-product 12.Crystal Structure Determination of the Piperidin-2-one 5.·Data were collected on an Enraf-Nonius CAD-4 diffractometer (Mo radiation, graphite monochromator, w-2y scans) at 20 °C. The crystal data and experimental parameters are summarised in the Table. The final cell parameters were determined using the Celdim routine.It was not found necessary to apply decay or absorption corrections to the data. The data were reduced to give the number of unique reflections and those with |F|a4s|F| were used in the structure solution and refinement. The structure was solved by automatic direct methods using SHELXS-8615 and refined by full-matrix least-squares analysis on F2 with SHELXL.16 The non-hydrogen atoms were refined anisotropically and all the hydrogen atoms were located from subsequent difference Fourier maps and refined with individual temperature factors to a final R value of 5.2%.Techniques used: IR, 1H NMR, 13C NMR, CH COSY and NOE, X-ray crystallography, elemental analysis References: 16 Table 1: Atomic coordinates and equivalent isotropic displacement parameters for 5 Table 2: Bond lengths and angles for 5 Table 3: Anisotropic displacement parameters for 5 Table 4: Mp, yield and IR data for 7c–e Table 5: Microanalytical data for 7c–e Table 6: NMR data for 7c–e Received, 19th August 1996; Accepted, 5th November 1996 PaperE/6/05767E References cited in this synopsis 1 (a) D.W. Robertson, E. E. Beedle, J. K. Swartzendruber, N. D. Jones, T. K. Elzey, R. F. Kauffman, H. Wilson and J. S. Hayes, J. Med. Chem., 1986, 29, 635; (b) M. D. Taylor, I. Sircar and R. P. Steffen, Annu. Rep. Med. Chem., 1987, 22, 87; (c) P. Dorigo, R. M. Gaion, P. Belluco,D. Fraccerollo, I. Maragno, G. Bombieri, F. Benetollo, L. Mosti and F. Orsini, J. Med.Chem., 1993, 36, 2475. 2 J. S. Wai, T. M. Williams, D. L. Bamberger, T. E. Fisher, J. M. Hoffman, R. J. Hudcosky, S. C. MacTough, C. S. Rooney, W. S. Saari, C. M. Thomas, M.E. Goldman, J. A. O’Brien, E. A. Emini, J. H. Numberg, J. C. Quintero, W. A. Schlief and P. S. Anderson, J. Med. Chem., 1993, 36, 249. 3 V. Doll�e, E. Fan, C. H. Ngugen, A.-M. Aubertin, A. Kim, M. L. Andreola, G. Jamieson, L. Tarrago-Litvak and E. Bisagui, J. Med. Chem., 1995, 38, 4679. 5 Z. Bomika, M. B. Andaburskaya, J. Pelcers and G. Duburs, Khim. Geterosikl. Soedin., 1975, 1108 (Chem. Abstr., 1975, 83, 193035). 6 Z. Bomika, G. Dubur, A. Krauze and E. Liepins, Khim. Geterosikl. Soedin., 1979, 1377 (Chem. Abstr., 1980, 92, 94201). 7 M. M. Al-Arab, J. Heterocycl. Chem., 1990, 27, 523. 8 C. N. O’Callaghan, T. B. H. McMurry, C. J. Cardin and D. J. Wilcock, J. Chem. Soc., Perkin Trans. 1, 1993, 2749. 15 G. M. Sheldrick, Acta Crystallogr., Sect. A, 1990, 46, 467. 16 G. M. Sheldrick, SHELXL 93, Program for Crystal Structure Refinement, University of G�ottingen, G�ottingen, 1993. J. CHEM. RESEARC

ISSN:0308-2342    

DOI:10.1039/a605767e

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 52–53† Zeolite-catalysed Selective Decomposition of Cumene Hydroperoxide into Phenol and Acetone† Manickam Sasidharan and Rajiv Kumar* Catalysis Division, National Chemical Laboratory, Pune-411 008, India Crystalline, microporous molecular sieves efficiently catalyse the selective decomposition of cumene hydroperoxide into phenol and acetone, both under batch (25 °C) and down-flow fixed-bed (60 °C) conditions; large-pore high-silica zeolites, mainly zeolite Beta and its metallo-silicate (B-, Fe- and Ga-silicate) analogues, are found to be particularly useful catalysts in this reaction giving ca. 92�3% phenol selectivity. Owing to their Br�onsted acidity, shape selectivity and thermal stability, crystalline microporous aluminosilicates, commonly known as zeolites, have been extensively used as environmentally friendly heterogeneous catalysts in a variety of organic transformations.1,2 Phenol is an industrially important chemical generally produced via acid-catalysed decomposition of cumene hydroperoxide.3 Various Br�onsted and Lewis acids in homogeneous systems4–7 at 0–50 °C and cation exchange resins in pseudo-heterogeneous systems8–10 have been reported as catalysts for cumene hydroperoxide decomposition. Phenol selectivity in the presence of an acid catalyst such as sulfuric acid was in the range 95–98% with more than 99% conversion.11 Commercially, the concentrated cumene hydroperoxide (CHP) solution is cleaved in the presence of sulfuric acid catalyst, the phenol yield being 95–98% mol%.The cleavage effluent, containing the acid used as catalyst as well as formic and acetic acids, formed as by-products, has to be neutralized and extracted to avoid corrosion and environmental problems.12 Now we report, for the first time, an efficient catalytic conversion of cumene hydroperoxide into phenol and acetone using solid zeolite catalysts under heterogeneous liquidphase conditions both in a batch and fixed-bed reactor system at between room temperature and 60 °C.Experimental In a typical batch experiment, to a solution of cumene hydroperoxide (2 g; 20% solution in cumene) in a 50 ml round bottomed flask was added the zeolite catalyst (0.2 g), obtained according to a known literature procedure.13–16 After completion of the reaction, the solid catalyst was filtered off before the products were analysed. In a fixed-bed down-flow reactor system, the H-form of the catalyst (zeolite Beta) was made into pellets (20–30 mesh size), and the binder-free zeolite (1 g anhydro.) was loaded at the centre of the down-flow silica-reactor (1 cm i.d., 30 cm length) using porcelain beads as the inert material.Cumene hydroperoxide (20% solution in cumene; 2 ml hµ1) along with carrier gas nitrogen (40 ml minµ1) was fed through a syringe pump (Sage Instruments, USA). The reactor temperature was maintained by an electrical heater. The products were analysed by capillary gas chromatography (HP-5880, using FID detector).Results and Discussion Table 1 indicates that the reaction was completed within 5 min at 25 °C and the phenol selectivity was 90�2% in all the cases where zeolite Beta analogues were used as catalyst (entries 1–4). Entries 2–4 suggest that not only aluminosilicate zeolites but their Fe, Ga or B analogues can also be effectively used as catalyst. The phenol selectivity is slightly higher for Fe, Ga and B-Beta samples.Zeolite ZSM-5 (entries 5–7) and Mordenite (entry 8) are also quite efficient catalysts. However, with these catalysts the phenol selectivity is slightly lower (86–88.5%) compared to that exhibited by Beta zeolites (88–95%). Over zeolite Y (entry 9), the conver- 52 J. CHEM. RESEARCH (S), 1996 *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem.Research (M). Table 1 Catalytic decomposition of cumene hydroperoxide over various zeolites SiM Reaction Conversion Phenol selectivity Entry Zeolite Ratioa Tb/°C time/min mass% mol% 123456789 10 11 12 13 14 15 16 17 18 19 H-[Al]-Bta H-[Ga]-Beta H-[Fe]-Beta H-[B]-Beta H-[Al]-ZSM-5 H-[Ga]-ZSM-5 H-[Fe]-ZSM-5 H-Mordenite H-Y H-[Al]-ZSM-12 H-[Al]-NCL-1 H-[Al]-ZSM-22 H-[Al]-MCM-22 H-[Al]-ZSM-48 H-[Al]-EU-1 H-SAPO-5 H-AlPO-5 H-[Al]-Betac No catalyst 14 20 22 30 30 35 30 7.0 2.5 40 40 60 30 50 50 —— 14 — RT RT RT RT RT RT RT RT 40 40 40 40 40 60 60 60 60 60 — 55555555 10 30 15 15 15 60 30 60 60 60 — 100 100 100 100 100 100 100 100 96.0 95.0 85.0 65.0 90.0 45.0 80.0 10.0 25.0 99.0 — 88.0 92.0 91.0 92.0 86.0 88.5 88.0 86.5 85.0 82.0 83.5 87.5 87.0 80.0 88.7 88.0 86.0 95.0 — aM=Al, Ga or Fe.bRT=room temperature. cFixed bed reaction: temperature=60 °C, catalyst=H-Beta (1 g), feed rate=2 ml hµ1, carrier gas=nitrogen (40 ml minµ1). Products were collected after 1 h.Mordenite and H-Y zeolites were obtained from Degussa, other catalysts were prepared according to the corresponding referenced method. The selectivity of phenol was confirmed by GC-5880 using a capillary column. The other products include quinones, catechol, acetophenone and higher boiling products such as a-methylstyrene and a-cumylphenol.sion was slightly less (96%) and the phenol selectivity was ca. 85%. However, over ZSM-12,13 NCL-1,14 ZSM-22,13 EU-1,13 MCM-2215 and ZSM-4813 (entries 10–15), lower conversions as well as selectivities were obtained.Medium-pore zeolites with unidimensional channels, such as ZSM-22, ZSM-48 and EU-1, exhibit lower conversions and selectivities due to diffusional restrictions imposed by the channel system of these zeolites on the reactant and products. However, large-pore unidimensional zeolites, such as ZSM-12, NCL-1 and MCM- 22, show ca. 85–90% conversion and selectivity.Entries 16 and 17 show the conversions and selectivities of cumene hydroperoxide over AlPO4-516 and SAPO-517 molecular sieves. Unlike aluminosilicates with strong Br�onsted acidity, aluminophosphates (neutral) and silicoaluminophosphates (weak Br�onsted acidity) exhibit lower activity in the cumene hydroperoxide decomposition, clearly suggesting the requirement of strong Br�onsted acid-sites for the decomposition of cumene hydroperoxide into phenol and acetone.The above results indicate that strong Br�onsted acid sites are needed for this reaction. Since Beta, ZSM-5 and Mordenite possess stronger acid sites compared to zeolites like Y, ZSM-22, ZSM-48, etc.,18,19 the conversion is complete using the former. Furthermore, with the reaction being quite fast, the quick diffusion of the reactants into the zeolite channels and of the products from the zeolite channels (as is the case of zeolite Beta with three-dimensional 12-membered-ring large-pore channels) will reduce the formation of secondary products such as quinones, a-methylstyrene, catechol, etc. and also the small amount of acetophenone.Hence it may be stated that a combination of strong Br�onsted acid sites and large pore intersecting channels in a high silica zeolite catalyst is suitable for this reaction. Entry 18 exhibits the results obtained using a fixed-bed, down-flow reactor giving 95% phenol selectivity at 99% conversion. The advantages of fixed-bed reaction conditions are: (i) there is no need to separate the solid catalyst from the products and (ii) higher phenol selectivities are obtained.These preliminary studies under unoptimised reaction conditions suggest the feasibility of the use of solid catalysts to replace environmentally hazardous mineral acids like sulfuric acid catalysts in CHP cleavage. Since under fixed-bed conditions the deactivation of the catalyst with time-on-stream is an important parameter, the effect of time-on-stream on activity and selectivity for the decomposition of cumeme hydroperoxide into phenol and acetone under fixed-bed conditions using H-Al-Beta catalyst was studied (Fig. 1). The time-on-stream data show that over 10 h, while the conversion remained the the phenol selectivity decreased slightly from ca. 95 to 90%. The successful use of a zeolite catalyst is thus demonstrated for the first time. Another advantage is that the zeolite can be regenerated in situ, regaining the initial activity and selectivity. Received, 24th July 1996; Accepted, 21st October 1996 Paper E/6/05186C References 1 R.P. Townsend, The Properties and Application of Zeolites, The Chemical Society, London, special publication no. 33, 1980. 2 W. F. H�olderich, M. Hesse and F. N�aumann, Angew. Chem., Int. Ed. Engl., 1988, 27, 226. 3 H. Hocks and S. Loung, Ber. Dtsch. Chem. Ges., 1944, 77, 257. 4 H. Hock, Angew. Chem., 1957, 69, 313. 5 R.A. Sheldon and J. A. Van Doorn, Tetrahedron Lett., 1973, 1021. 6 N. C. Deno, W. E. Billups, K. E. Kramer and R. R. Lastomirsky, J. Org. Chem., 1970, 35, 3080. 7 J. O. Turner, Tetrahedron Lett., 1971, 887. 8 R. M. Barrer, Hydrothermal Chemistry of Zeolites, Academic Press, London, 1982, pp. 251. 9 R. Szostak and T. L. Thomas, J. Catal., 1979, 59, 269. 10 J. Vodnar, P. Fejes, K. Varga and F. Berrger, Appl. Catal., 1995, 122, 33 and references cited therein. 11 K. Weissermel and H.-J. Arpe, Industrial Organic Chemistry, VCH, Weinheim, 2nd edn., 1993, p. 351. 12 K. Othmer, Encyclopedia of Chemical Technology, ed. Mary Howe-Grant, Wiley, New York, 4th edn., 1996, vol. 18, p. 596. 13 P. A. Jacobs and J. A. Martens, Stud. Surf. Sci. Catal., 1989, 33, 12, 22. 14 R. Kumar, K. R. Reddy and P. Ratnasamy, U.S. Pat., 5 219 813, 1993. 15 R. Ravishankar, T. Sen, V. Ramaswamy, H. S. Soni, S. Ganapathy and S. Sivasanker, Stud. Surf. Sci. Catal., 1994, 84, 331. 16 S. T. Wilson, B. M. Lok, C. A. Messina, T. R. Cannon and E. M. Flanigen, J. Am. Chem. Soc., 1982, 104, 1146. 17 B. M. Lok, C. A. Messina, R. L. Patton, R. T. Gajek, T. R. Cannan and E. M. Flanigen, J. Am. Chem. Soc., 1984, 106, 6092. 18 S. G. Hegde, R. N. Bhat, R. Kumar and P. Ratnasamy, Zeolites, 1989, 9, 233. 19 V. R. Chaudhary, A. P. Singh and R. Kumar, J. Catal., 1991, 129, 293. J. CHEM. RESEARCH (S), 1996 53 Fig. 1 Decomposition of cumene hydroperoxide into phenol and acetone over zeolite Beta (Si/Al=14): temperature=60 °C, LHSV, 2 hµ1; Conv=cumene hydroperoxide conversion, mol%; Sel=phenol selectivity,

ISSN:0308-2342    

DOI:10.1039/a605186c

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 54–55† Flash-photolysis Study of Potassium Hydroxide Solutions† M�onica C. Gonzalez* and Daniel O. M�artire Instituto de Investigaciones Fisicoqu�ýmicas Te�oricas y Aplicadas (INIFTA), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, (1900) La Plata, Argentina Flash-photolysis experiments of KOH solutions ([KOH]a0.03 M) are carried out in hydrogen- and air-saturated solutions; the formation of hydrated electrons is observed in hydrogen-saturated solutions, but the formation of O2 .µ and O3 .µ is observed in the presence of molecular oxygen and a reaction mechanism supported by kinetic computer simulations of the results is proposed.The dissociation threshold energy of water, yielding H. atoms and HO. radicals, lies in the region 6.41–6.71 eV.1 Accordingly, photodissociation of water [eqn. (1a)]2 has been reported to occur with quantum efficiencies of the order of 0.3 at 184.9 nm, 0.7 at 147.9 nm, and approaching 1 at 123.6 nm.In addition to eqn. (1a), the photolytic formation of eµ aq from eqn. (1b) has already been demonstrated in flash-photolysis experiments for photons of 6.54 eV.6 Experiments using the formation of fluoride ions from SF6 as a specific monitor for eµ aq indicate that photolysis of water in the wavelength range 175–200 nm produces hydrated electrons with a constant quantum yield of 0.05�0.01 at pH 4–9,3,4 increasing slowly with the irradiation energy.5 The observed independence of the quantum yields on pH was suggested as an indication that water, but not HOµ, is a source of eµ aq.An increase in the quantum yield above pH 9 was reported to be due to the reaction between H. and HOµ yielding eµ aq [eqn. (10)]. However, photoionization of OHµ, eqn. (2), has been proposed as the main reaction in H2-saturated KOH solutions.3 Photolysis of alkaline H2-saturated solutions has been reported as a nearly ideal source of eµ aq, since the reactions [eqns.(15) and (10)] add to the yields of hydrated electron produced from eqns. (1) and (2). However, no studies have been reported on the photolysis kinetics in oxygen- or airsaturated KOH solutions. Here we report the results of our flash-photolysis studies in the presence of dissolved oxygen, which turned out to be a rather clean method of ozonide radical generation. Experimental KOH (Mallinckrodt) was used without further purification.Distilled water was passed through a Millipore system and deaerated in order to avoid dissolution of carbon dioxide. Flash-photolysis experiments were carried out in a conventional apparatus (Xenon Co. model 720C) with modified optics and electronics.7 For observation wavelengths higher than 600 mm, a 500 nm cut-off filter was placed in front of the monochromator in order to eliminate detection of harmonics. In those experiments where detection above 650 nm was necessary, high analysing lamp intensities were required due to the low sensitivity of the photomultiplier (PMT) at these wavelengths.Under these conditions, detection at lower wavelengths (higher PMT sensitivity) required amplification values almost below the limit of the recommended range of linear responsivity of the PMT. This may be the cause of the discrepancy between our spectrum and that reported, both of which are shown in Fig. 1. In order to detect the formation of hydrated electrons, aqueous solutions of KOH (pHa12.5) degassed by three freeze-pump-thaw cycles were saturated with almost 1 atm of H2 and the cell was sealed.The solutions were irradiated for 10–20 min with a continuous mercury lamp, prior to the flash-photolysis experiments, in order to eliminate traces of oxygen and/or organic material.3 Photolysis studies of KOH in the presence of dissolved oxygen were performed in synthetic air-saturated solutions in order to avoid CO2 dissolution.The presence of CO3 2µ in the solutions was checked by flash irradiation experiments at 600 nm (lmax of CO3 .µ absorption8). Results and Discussion The absorption traces observed immediately after pulsed irradiation of H2-saturated KOH solutions showed a decay lifetime of the order of 0.5 ms and an absorption spectrum with a maximum around 715 nm, Fig. 1. Both the absorption spectrum and the decay lifetime are in agreement with reported values for the hydrated electron,3,9 thus indicating hydrated electron formation under our experimental conditions.On the other hand, the absorption traces observed after flash irradiation of KOH solutions saturated with synthetic air show a complex dependence on wavelength in the range 260–500 nm, indicating the absorption of more than one species. Fig. 2 shows the traces observed at 440 and 270 nm (inset), respectively. In the presence of molecular oxygen, solvated electrons and H. atoms are known to be efficiently scavenged by molecular oxygen, yielding O2 .µ/HO2 ., eqns.(4) and (11), respectively. Moreover, in strongly alkaline solutions, OH. radicals formed in the primary photochemical steps efficiently react with OHµ ions yielding O.µ, eqn. (13), which in the presence of molecular oxygen yields O3 .µ radical ions in a reversible reaction [eqns. (20) and (24)]. In fact, the absorption spectrum observed for irradiation wavelengths a300 nm agrees with that reported for O3 .µ10–15 and the build-up signal observed at 270 nm can be assigned to the absorption of O2 .µ, which is known to be relatively highly stable in alkaline solutions (free of catalytic amounts of metal impurities which may catalyse its decomposition).16 The participation of reactive HO., H.and eµ aq during flash photolysis of KOH solutions resembles the radiation chemistry of aqueous solutions and so the extensive information reported on these systems can be used. A set of well established reactions reported in the literature and involving the species present in the irradiated system are listed in Table 1.17–19 Those reactions whose participation was considered to 54 J.CHEM. RESEARCH (S), 1996 *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Fig. 1 Absorption spectrum of eµ aq.Data taken from ref. 3 represented by ——— and experimental data obtained in this work represented by s (uncorrected spectrum, refer to text for details)be negligible under our experimental conditions were omitted for simplicity. A detailed discussion on some of these reactions and on the establishment of HO./O.µ and O3 .µ/O.µ equilibria conditions can be found elsewhere.20 An ab initio computer program based on the numerical resolution of the differential equations system by the Runge Kutta method was used in order to simulate the reaction kinetics.20 The program considers the flash emission as a delta function, producing HO.radicals, hydrogen atoms and hydrated electrons. The initial concentrations of these transient species present after the pulse of light were handled as input parameters. According to eqns. (1a,b) and (2), the stoichiometry condition [HO.]0=[H.]0+[eµ aq]0 was considered. The simulation concentration profiles of O2 .µ and O3 .µ are not sensitive to the [eµ aq]0:[H.]0 ratio used as input parameter, as suggested by the participation of the efficient reaction [eqn.(10)] readily converting H. atoms into hydrated electrons. Those [HO.]0 values which best fitted the experimental concentrations of O3 .µ were used for the simulations. The simulated O2 .µ and O3 .µ concentration profiles obtained at 270 and 440 nm, respectively, are shown in Fig. 2. An acceptable agreement between simulated and experimental profiles supports the proposed mechanism.Any low-intensity emission of the flash lamp below 200 nm is efficiently absorbed by the water contained in the 0.8 cm pathlength thermostat jacket. Consequently, H2O photodissociation [eand 1(b)] is expected to be negligible and photoionization of HOµ ions [eqn. (2)] should be the main photochemical reaction in the present system. M. C. G. and D. O. M. are research members of CONICET and CICPBA (Argentina), respectively.This research was partially supported by the grants number A-13218/1-000062 and A-13359/1-000084 of Fundaci�on Antorchas (Argentina). Received, 12th September 1996; Accepted, 21st October 1996 Paper E/6/06288A References 1 D. N. Nikogosyan and H. G�orner, J. Photochem. Photobiol. B: Biol., 1992, 13, 219. 2 J. Barret and J. H. Baxendale, Trans. Faraday Soc., 1960, 56, 37; U. Sokolov and G. Stein, J. Chem. Phys., 1965, 44, 2189, 3329; Radiation Chemistry in Aqueous Systems, ed.G. Stein, Weizmann Science Press, Jerusalem, 1968, pp. 83–89, and references cited therein. 3 E. J. Hart and M. Anbar, in The Hydrated Electron, Wiley–Interscience, New York, 1970; D. Phillips, in Photochemistry, The Chemical Society, London, 1973, vol. 4, part II, p. 366 and references cited therein. 4 K.-D. Asmus and J. H. Fendler, J. Phys. Chem., 1969, 73, 1583. 5 G. O. Schenck and N. Getoff, Proc. Int. Conf. Photochem., 1967, 2, 720. 6 J. W. Boyle, J. A. Ghormley, C.J. Hochanadel and J. F. Riley, J. Phys. Chem., 1969, 73, 2886. 7 E. San Rom�an, P. F. Aramend�ýa and H. J. Schumacher, An. Asoc. Qu�ým. Argent., 1980, 70, 887. 8 G. L. Hug, Nat. Stand. Ref. Data Ser. (U.S. Nat. Bur. Stand.), 1981, 69, 30 and references cited therein. 9 K. Schmidt and E. J. Hart, ACS Adv. Chem., 1968, 81, 267 and references cited therein. 10 K. Sehested, J. Holcman, E. Bjerbakke and E. J. Hart, J. Phys. Chem., 1982, 86, 2066. 11 R. E. B�uhler, J. Staehelin and J.Hoign�e, J. Phys. Chem., 1984, 88, 2560. 12 G. Czapski and L. M. Dorfman, J. Phys. Chem., 1964, 68, 1169. 13 G. E. Adams, J.W. Boag and B. D. Michael, Nature (London), 1965, 205, 898. 14 G.E. Adams, J.W. Boag and B.D. Michael, Proc. R. Soc. London, A, Math. Phys. Sci., 1966, 289, 321. 15 L. J. Heidt and B. R. Landl, J. Chem. Phys., 1964, 41, 176. 16 B. H. J. Bielski, Methods Enzymol., 1984, 105, 81; B. H. J. Bielski and R. L. Araudi, Anal. Biochem., 1983, 133, 170. 17 P. Neta, R.E. Nuie and A. B. Ross, J. Phys. Chem. Ref. Data, 1988, 17, 1027. 18 Fahataziz and A. B. Ross, Selected Specific Rates of Reactions of Transients from Water in Aqueous Solutions. Part II. Hydroxyl Radical and Perhydroxyl Radical and their Radical Ions. NSRDSNBS 59, National Bureau of Standards, Washington DC, 1977. 19 G. V. Buxton, C. L. Greenstock, W. P. Helman and A. B. Ross, J. Phys. Chem. Ref. Data 1988, 17, 513. 20 M. C. Gonzalez and D. O. M�artire, Int. J. Chem. Kin., in the press.J. CHEM. RESEARCH (S), 1996 55 Fig. 2 Experimental (---) and simulated (———) absorbance traces for absorption curves as obtained for O3 .µ decay (440 nm) and O2 .µ build-up at 270 nm (inset) in 1 M KOH containing 2.5Å10µ4 M O2. Optical path length 20 cm, e(O3 .µ)440 nm=1900 dm3 molµ1 cmµ18 and e(O2 .µ)270 nm=1360 dm3 molµ1 cmµ1 10 were used in the calculations Table 1 Important reactions taking place during UV irradiation of alkaline water Reaction Rate constant k/dm3 molµ1 sµ1 H2O+hvhHO.+H. (1a) H2O+hvhHO.+H++eµ aq (1b) HOµ+hvhHO.+eµ aq (2) eµ aq+eµ aq (+H2O)hH2+2HOµ (3) 5.5Å109 eµ aq+O2hO2 .µ (4) 1.9Å1010 eµ aq+H.hH2+HOµ (5) 2.5Å1010 eµ aq+HO.hHOµ (6) 3.0Å1010 eµ aq+O.µ (+H2O)h2HOµ (7) 2.2Å1010 H.+H.hH2 (8) 7.7Å109 H.+HO.hH2O (9) 7.0Å109 H.+OHµhH2O+eµ aq (10) 2.2Å107 H.+O2hHO2 . (11) 2.1Å1010 HO.+HO.hH2O2hH++HO2 µ (12) 5.5Å109 HO.+HOµhH2O+O.µ (13) 1.3Å1010 HO.+O.hHO2 µ (14) R2Å1010 HO.+H2hH2O+H. (15) 4.2Å107 HO.+HO2 µhHOµ+HO2 . (16) 7.5Å109 HO.+O2 .µhO2+HOµ (17) 8.0Å109 O.µ+H2OhHOµ+HO. (18) 1.8Å106 O.µ+O.µ (+H2O)hHO2 µ+HOµ (19) 8.0Å109 O.µ+O2hO3 .µ (20) 3.6Å109 O.µ+H2hHOµ+H. (21) 8.0Å107 O.µ+HO2 µhHOµ+O2 .µ (22) 4.0Å108 O.µ+O2 .µ+H2OhO2+2HOµ (23) 6.0Å108 O3 .µhO.µ+O2 (24) 3.6–6.0Å103a O.µ+O3 .µhO2 .µ+O2 .µ (25) 8.0Å108 HO.+O3 .µhH++2O2 .µ (26) 1.1Å1010 O2 .µ+O2 .µhO2+HOµ+HO2 µ (27) s102 O3 .µ+O2 .µ+H2Oh2HOµ+2O2 (28) 5.0Å104 aU

ISSN:0308-2342    

DOI:10.1039/a606288a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 56–57† Regioselectivity in the Hydroboration of Steroidal D3-Allylic Alcohols† Muzaffar Alam, James R. Hanson,* Mansur Liman and Sivajini Nagaratnam School of Molecular Sciences, University of Sussex, Brighton, Sussex BN1 9QJ, UK The presence of an allylic 5a-hydroxy group in an androst-3-ene increases the proportion of addition of a borane to the adjacent C-4 compared to the unsubstituted steroid and directs the addition to the face of the alkene anti to the hydroxy group with stereochemical effects that may oppose those of the C-10b-methyl group.Hydroboration proceeds in a cis-manner on the less-hindered face of an alkene with anti-Markownikoff regioselectivity.1,2 The directing effects of electronegative substituents in allyl derivatives modify the regiospecificity favouring addition of the borane at the 2-position.3 In cyclohex-2-en-1-ols, the hydroxy group also affects the stereospecificity and directs the addition of the borane to the opposite face of the alkene.4 Other directing effects in cyclic systems may arise from transannular diaxial interactions between the borane and sterically bulky groups.The relative contributions of these effects require evaluation. In the steroid series, the directing effect of an allylic hydroxy group on the hydroboration of the trisubstituted alkene, androst-4-ene, is sufficient to overturn the normal directing effect of the C-10 methyl group. The C-10 angular methyl group can also affect the stereochemistry of reactions of the disubstituted androst-3-enes.The absence of a Markownikoff effect can afford greater potential for an adjacent hydroxy group to modify both the regiochemistry and stereochemistry of hydroboration. The hydroboration of 17b-acetoxy-5a-hydroxyandrost-3-ene and 17b-acetoxy-5a-hydroxy-19-norandrost-3-ene was compared to 17b-acetoxy-5a-androst-3-ene and 17b-acetoxy-19-nor- 5a-androst-3-ene to contrast the directing role of the 10b- methyl group with that of the pseudo-axial 5a-hydroxy group.The results are shown in Table 1. The structures of the products were readily established from the multiplicity of the CH(OH) resonances in the 1H NMR spectra6 and by comparison with literature data.7 The 5a-hydroxy group increased the proportion of addition at C-4 in the hydroboration of androst-3-enes despite the fact that this is a more hindered position than C-3. The trans directing effect of the 5a-hydroxy group opposed the steric hindrance of the 10b-methyl group and increased the amount 56 J.CHEM. RESEARCH (S), 1996 *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Table 1 Yields (%) of hydroboration products of androst-3-enesof addition to the b-face of the 3-ene. In the case of the 19-nor steroid, lacking this methyl group, only products arising from addition to the b-face were obtained when a 5a- hydroxy group was present. Comparison of the results of hydroboration of 5a-hydroxyandrost-3-ene and the corresponding 19-nor steroid suggests that the 10b-methyl group and the 5a-hydroxy group have approximately equivalent directing effects.Experimental General experimental details have been described previously.5 Steroids were crystallized from ethyl acetate or acetone–light petroleum mixtures.Hydroboration Experiments.·17b-Acetoxy-5a-androst-3-ene. The steroid (1 g) in dry THF (30 cm3) was treated with borane in THF (30 cm3, 1 M) for 4 h. Water (10 cm3) was added and the solution cooled to 0 °C. Aqueous sodium hydroxide (20 cm3, 10%) was added followed by the dropwise addition of hydrogen peroxide (20 cm3, 30%). The mixture was stirred overnight. Sodium sulfite (2 g) was added followed by acetic acid (1 cm3), water (50 cm3), dil.hydrochloric acid (50 cm3) and ethyl acetate (100 cm3). The organic layer was separated, washed with water, brine and then dried. The solvent was evaporated and the residue chromatographed on silica. Elution with 25% ethyl acetate–light petroleum gave successively (i) 3b,17b-dihydroxy-5a-androstane (64 mg), needles, mp 167–169 °C (lit.,7 168–169 °C), vmax/cmµ1 3450, 3304; dH (3 H, s, 18-H), 0.79 (3 H, s, 19-H), 3.61 (2 H, m, 3a- and 17a-H); (ii) 4a,17b-hydroxy-5a-androstane (263 mg), prisms, mp 231–233 °C (lit.,8 235–237 °C), vmax/cmµ1 3506, 3433; dH 0.73 (3 H, s, 18-H), 0.81 (3 H, s, 19-H), 3.45 (1 H, dt, J 4.6 and 10.5 Hz, 4b-H), 3.63 (1 H, t, J 8.6 Hz, 17a-H); (iii) 4b,17b-dihydroxy-5a-androstane (92 mg), needles, mp 179–181 °C (lit.,8 176–178 °C), vmax/cmµ1 3490, 339; dH 0.72 (3 H, s, 18-H), 0.99 (3 H, s, 19-H), 3.62 (1 H, t, J 8.6 Hz, 17a-H), 3.88 (1 H, m, 4a-H); (iv) 3a,17b-dihydroxy-5a-androstane (278 mg), prisms, mp 220–223 °C (lit.,7 222–224 °C), vmax/cmµ1 3490, 3400; dH 0.73 (3 H, s, 18-H), 0.79 (3 H, s, 19-H), 3.62 (1 H, t, J 8.6 Hz, 17a-H), 4.05 (1 H, brs, 3b-H). 17b-Acetoxy-19-nor-5a-androst-3-ene. The 19-nor steroid (1 g) gave (i) 4b-17b-dihydroxy-19-nor-5a-androstane (63 mg), needles, mp 167–169 °C (Found: C, 77.5; H, 10.8. C18H30O2 requires C, 77.6; H, 10.9%); vmax/cmµ1 3305; dH 0.74 (3 H, s, 18-H), 3.64 (1 H, t, J 8.2 Hz, 17a-H), 3.76 (1 H, brs, 4a-H); (ii) 4a,17b-dihydroxy-19-nor- 5a-androstane (240 mg), plates, mp 200–220 °C (Found: C, 77.5; H, 10.9.C18H30O2 requires C, 77.5; H, 10.9%); vmax/cmµ1 3230; dH 0.75 (3 H, s, 18-H), 3.21 (1 H, td, J 10.5 and 4.6 Hz, 4b-H), 3.64 (1 H, t, J 8.2 Hz, 17a-H); (iii) 3a,17b-dihydroxy-19-nor-5a-androstane (145 mg), needles, mp 163 °C (Found: C, 77.6; H, 11.0. C18H30O2 requires c, 77.6; H, 10.9%); vmax/cmµ1 3279; dH 0.72 (3 H, s, 18-H), 3.64 (1 H t, J 8.2 Hz, 17a-H), 4.12 (1 H, brs, 3b-H); (iv) 3b,17b-dihydroxy- 19-nor-5a-androstane (120 mg), needles, mp 141–143 °C (Found: C, 77.5; H, 10.7.C18H30O2 requires C, 77.6; H, 10.9%); vmax/cmµ1 3348; dH 0.74 (3 H, s, 18-H), 3.57 (1 H, t, J 10.5 and 4.5 Hz, 3a-H) 3.62 (1 H, t, J 8.1 Hz, 17a-H). 17b-Acetoxy-5a-hydroxyandrost-3-ene. The 5a-hydroxy steroid (1 g) gave 4a,17b-dihydroxy-5a-androstane (147 mg) and 4b,17b-dihydroxy-5b-androstane (30 mg) which were identified by their 1H NMR spectra. Further chromatography gave 4a,5a,17b-trihydroxyandrostane (90 mg), prisms, mp 219–220 °C (Found: C, 71.7; H, 10.3.C19H32O3.0.5H2O requires C, 71.9; H, 10.5%); vmax/cmµ1 3498, 3409, 3335; dH 0.73 (3 H, s, 18-H), 0.94 (3 H, s, 19-H), 3.65 (2 H, m, 4b- and 17a-H). The 4a,17b-diacetate, prepared with acetic anhydride in pyridine, had mp 170–172 °C (Found: C, 70.7; H, 9.5. C23H36O5 requires C, 70.4; H, 9.2%); vmax/ cmµ1 3380, 1720; dH 0.71 (3 H, s, 18-H), 0.91 (3 H, s, 19-H), 1.96 and 1.99 (each 3 H, s, OAc), 4.51 (1 H, t, J 7.8 Hz, 17a-H), 4.91 (1 H, dd, J 6.0 and 10.5 Hz, 4b-H).Further chromatography gave 4b,5a,17b-trihydroxyandrostane (281 mg), prisms, 223–225 °C (Found: C, 71.5; H, 10.3. C19H32O3.0.5H2O requires C, 71.9; H, 10.5%); vmax/cmµ1 3490, 3400, 3367; dH 0.74 (3 H, s, 18-H), 1.18 (3 H, s, 19-H), 3.54 (1 H, t, J 2.8 Hz, 4a-H), 3.64 (1 H, t, J 8.4 Hz, 17a-H). The 4b,17b-diacetate, prepared with acetic anhydride in pyridine, had mp 181–183 °C (Found: C, 70.2; H, 9.0. C23H36O5 requires C, 70.4; H, 9.2%); vmax/cmµ1 3240, 1740, 1720; dH 0.74 (3 H, s, 18-H), 1.10 (3 H, s, 19-H), 1.96 and 1.99 (each 3 H, s, OAc), 4.54 (1 H, t, J 7.8 Hz, 17a-H), 4.65 (1 H, t, J 2.6 Hz, 4a-H).Further elution gave 3b,5a,17b-trihydroxyandrostane (201 mg), mp 192–194 °C (lit.,9 193–196 °C). 17b-Acetoxy-5a-hydroxy-19-norandrost-3-ene. The 5a-hydroxy- 19-nor steroid (1 g) gave successively (i) 5a,17b-dihydroxy-19-norandrostane (40 mg) as a gum, m/z 292 (M+), 274 (MµH2O) 256 (Mµ2H2O); vmax/cmµ1 3512; dH 0.75 (3 H, s, 18-H), 3.65 (1 H, t, J 8.2 Hz, 17a-H); (ii) 17b-acetoxy-4b,5a-dihydroxy-19-norandrostane (160 mg), plates, mp 187–189 °C (Found: C, 71.3; H, 9.7.C20H32O4 requires C, 71.4; H, 9.6%); vmax/cmµ1 3320, 1742; dH 0.78 (3 H, s, 18-H), 2.02 (3 H, s, OAc), 3.47 (1 H, t, J 3.0 Hz, 4a-H), 4.58 (1 H, t, J 8 Hz, 17a-H); (iii) 17b-acetoxy-3b,5a-dihydroxy-19-norandrostane (80 mg), needles, mp 218–220 °C (Found: C, 70.7; H, 9.6. C20H32O4 requires C, 71.4; H, 9.6%); vmax/cmµ1 3358, 1720; dH 0.75 (3 H, s, 18-H), 2.04 (3 H, s, OAc), 3.98 (1 H, tt, J 9.6 and 4.5 Hz, 3a-H), 4.62 (1 H, t, J 8.2 Hz, 17a-H); (iv) 4b,5a-17b-trihydroxy- 19-norandrostane (410 mg), prisms, 203–205 °C (Found: C, 71.5; H, 10.2.C18H30O3.0.5H2O requires C, 71.2; H, 10.3%); vmax/cmµ1 3450; dH 0.74 (3 H, s, 18-H), 3.48 (1 H, t, J 2.8 Hz, 4a-H), 3.65 (1 H, t, J 8 Hz, 17a-H). Received, 28th August 1996; Accepted, 22nd October 1996 Paper E/6/05946E References 1 A. Pelter and K. Smith, in Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, vol. 8, p. 703. 2 M. Husim, Y. Mazur and F. Sondheimer, J. Org. Chem., 1964, 29, 1420. 3 H. C. Brown and R. M. Gallivan, J. Am. Chem. Soc., 1968, 90, 2906. 4 E. Dunkelblum, R. Levene and J. Klein, Tetrahedron, 1972, 28, 1009. 5 J. R. Hanson, P. B. Hitchcock, M. Liman and S. Nagaratnam, J. Chem. Soc., Perkin Trans. 1, 1995, 2183. 6 J. E. Bridgeman, P. C. Cherry, A. S. Clegg, J. M. Evans, Sir Ewart R. H. Jones, A. Kasal, V. Kumar, G. D. Meakins, Y. Morisawa, E. E. Richards and P. D. Woodgate, J. Chem. Soc. C, 1970, 250. 7 Dictionary of Steroids, ed. R. A. Hill, D. N. Kirk, H. L. J. Makin and G. M. Murphy, Chapman and Hall, London, 1992. 8 D. Marcano and H. Rojas, Acta Cient. Venezolana, 1974, 25, 195. 9 S. Julia, P. A. Plattner and H. Heusser, Helv. Chim. Acta, 1952, 35, 665. J. CHEM. RESEARCH (S), 1996 57

ISSN:0308-2342    

DOI:10.1039/a605946e

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Membrane Carrier Selectivities Identified by CompetitionTransport Experiments Burkhard Ko ¡ì nig,*a Marc Mu¡ì ller,b Hubertus Wichmannb and Mu¡ì fit Bahadirb aInstitut fu ¡ì r Organische Chemie derTechnischen Universita¡ì t Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany bInstitut fu ¡ì r O¡ì kologische Chemie und Abfallanalytik derTechnischen Universita ¡ì t Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany With a single experiment the transport selectivity of a membrane carrier towards a given set of metal cations can be determined.Here we report an approach that facilitates the testing of carrier selectivities in the transport through supported and bulk liquid membranes.1a A single competition transport ex- periment with ten metal nitrates and subsequent simul- taneous metal ion analysis of the receiving phase with ICP- OES8 yields the transport selectivity pattern of a carrier for a given set of metal cations and the experimental conditions applied.The unrestricted choice of metal salts used in the procedure allows a rapid screening of membranes for separ- ation technology. However, it must be emphasized that the observed selectivities are only valid for the employed mix- ture: coupling between the movements of di€erent ions is likely in a multi-component system. Thereby transport rates might change with the source phase composition. Compound 1 is well known to bind and transport sodium ions selectively.9 However, complete selectivity was not expected and therefore 1 was used as a membrane carrier to investigate multielement transport experiments.By standard procedures 1 was incorporated into a porous polypropylene membrane with ortho-nitrophenyl octyl ether (NPOE) as sol- vent.7 The so obtained SLM was used in transport exper- iments with an aqueous source phase containing equimolar amounts (0.15 mol L¢§1) of ten nitrate salts. The analysis of the receiving phase after 168 h shows the expected high pre- ference for sodium nitrate transport (Fig. 1). However, some transport of potassium and lead nitrate was also detected. To monitor the entire transport process, i.e. the ion concen- tration of the source and receiving phase before and after ion .ux, lower salt concentrations had to be used. A source phase with ten nitrate salts, each of a concentration of 50 mg L¢§1, proved to be useful (Fig. 2). Competitive transport experiments were used to determine the transport properties of new or not yet tested carrier mol- ecules 2¡¾5 and 7.The results are summarized in Table 1. With benzo-crown[5] (6) as carrier, multielement competitive transport experiments trough BLMs were performed. Chloroform, dichloromethane or freon were used as the organic membrane phase. The transport selectivity patterns of 1 and 7¡¾9 in dichloromethane were measured accord- ingly. For podant 9 an unexpectedly high lead transport J. Chem. Research (S), 1998, 58¡¾59 J.Chem. Research (M), 1998, 0401¡¾0410 O O O O O O O O O O O 1 O N O H n 2 n = 6 3 n = 8 N N N O Bu H N Bu H O N N N O Bu H N Bu H O 4 O 6 5 O O O O O 6 O O O O O 2 7 S S Si S Si S Si Si 8 O O O O O 9 Fig. 1 Competitive transport of metal nitrates through an SLM with carrier1. Concentration in receiving phase after168 h; transport rates J are given in [10¢§8 molm¢§2 s¢§1]12 *To receive any correspondence. 58 J. CHEM. RESEARCH (S), 1998Fig. 2 Competitive transport of metal nitrates through an SLM withcarrier1. Concentration in source and receiving phase after168 h;transport rates J are given in [10£¾8 molm£¾2 s£¾1]Table 2 Carriermediated competitive transport through bulk liquidmembranesaCarrier Al Ca Cd Cu Fe K Mg Na Pb Zn6b ^c ^ ^ ^ ^ 0.2 ^ 2.4 0.01 ^6d ^ ^ ^ ^ ^ 24.6 ^ 10.7 0.14 ^6e ^ ^ ^ ^ ^ ^ ^ 0.1 ^ ^1f ^ ^ ^ ^ ^ 0.7 ^ 176 0.05 ^7g ^ ^ ^ ^ ^ 0.2 ^ ^ ^ ^8h ^ ^ ^ ^ ^ ^ ^ 1.7 ^ ^9f ^ ^ ^ ^ ^ 1.4 ^ 0.6 26 ^aAll rates are given in [10£¾8 mol m£¾2 s£¾1].12 Source phase concentration 0.15mol L£¾1 for eachmetal salt and dichloromethane bulk liquidmembrane unless otherwise stated.bSource phase concentration 1000 mg L£¾1 for eachmetal salt; chloroformas organic phase; 120 htransport time. cNot detected; concentration in receiving phase<0.2mg L£¾1. dSource phase concentration 1000mg L£¾1 for eachmetal salt;dichloromethane as organic phase; 120 h transport time eSource phase concentration 1000mg L£¾1 for eachmetal salt; freon(trichlorotrifluoroethane) as organic phase; 120 h transport time.f24 h transport time. g24 h transport time; chloroform bulk liquidmembrane.h48 h transport time.Table 1 Transport rates through supported liquid membranesaCarrier Al Ca Cd Cu Fe K Mg Na Pb Zn1b ^c ^ ^ ^ ^ 0.2 ^ 44.2 0.02 ^1b,d ^ ^ ^ ^ ^ ^ ^ 5.9 ^ ^2e ^ ^ ^ ^ ^ ^ ^ 2.8 ^ ^3e ^ ^ ^ ^ ^ ^ ^ 0.3 ^ ^4e ^ ^ ^ ^ ^ ^ ^ 5.3 ^ ^5e ^ ^ ^ ^ ^ ^ ^ ^ ^ ^6e ^ ^ ^ ^ ^ 45 ^ 1.6 0.4 ^7e ^ ^ ^ ^ ^ 13 ^ ^ 0.08 ^aAll transport rates are given in [10£¾8 mol m£¾2 s£¾1].12 Source phase concentration 0.15 mol L£¾1 for eachmetal salt unless otherwise stated.b Transport for 168 h. cNot detectable; concentration in receiving phase<0.2mg L£¾1.dSource phase concentration 50 mg L£¾1 for eachmetalsalt. e Transport for 24 h.rate was found in dichloromethane. The results are summar-ized in Table 2.In summary we have shown that the laborious testing ofmembrane carrier selectivities towards a given set of metalcations and specic conditions can be reduced to a singletransport competition experiment using ICP-OES for simul-tanous ion analysis.Technique used: ICP-OESReferences: 21Received, 16th July 1997; Accepted, 6th October 1997Paper E/7/05092EReferences and notes cited in this synopsis1 (a) F.de Jong and H. C. Visser, in Comprehensive Supra-molecular Chemistry, ed. J.-M. Lehn, J. L. Atwood, J. E. D.Davies, D. D. Macnicol, F. Vo gtle and D. N. Reinhoudt,Pergamon, Oxford, 1996, vol. 10, pp. 13¡Ó51.7 (a) T. B. Stolwijk, E. J. R. Sudho lter and D. N. Reinhoudt,J. Am. Chem. Soc., 1987, 109, 7042. (b) R. M. Izatt, R. L.Bruening, M. L. Bruening, G. C. LindH and J. J. Christensen,Anal. Chem., 1989, 61, 1140; (d) E. G. Reichwein-Buitenhuis,H. C. Visser, F. de Jong and D. N. Reinhoudt, J. Am. Chem.Soc., 1995, 117, 3913.8 (a) Inductively Coupled Plasmas in Analytical AtomicSpectrometry, ed. A. Montaser and D. W. Golightly, VCH,Weinheim, 2nd edn., 1992.9 M. A. McKervey, M.-J. Schwing-Weill and F. Arnaud-Neu,in Comprehensive Supramolecular Chemistry, ed. J.-M. Lehn,J. L. Atwood, J. E. D. Davies, D. D. Macnicol, F. Vo gtle andG. W. Gokel, Pergamon, Oxford, 1996, vol. 1, pp. 537¡Ó603 andreferences cited therein.12 The reported uxes are transient uxes for the given experimen-tal conditions. However, if the experiments are repeated fordierent periods of time a kinetic analysis of the competitivetransport is possible. From such measurements steady stateuxes can be derived. All experiments were performed at20(23) 8C. The solutions were constantly stirred at 50 rpm.J. CHEM. RESEARCH (S), 1998 59

ISSN:0308-2342    

DOI:10.1039/a705092e

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Palladium-catalysed Cyclisation and Cyclisation^ Carbonylation of Unsaturated C-Glycoside Derivatives. The Importance of Relative Stereochemistry CedricW. Holzapfel* and Lizel Marais Department of Chemistry and Biochemistry, Rand Afrikaans University, P.O. Box 524, Auckland Park, 2006, South Africa The Pd-catalysed `metallo-ene type' cyclisation and cyclisation^carbonylation of selected 2,3-unsaturated C-glycosides is described and attention is drawn to the importance of relative stereochemistry in the latter type of reactions.The palladium(0)-catalysed intramolecular carbocyclisation of allyl acetates with alkenes, a type of palladium-ene reaction,1 exempli¢çes an attractive methodology leading to usefully functionalised ¢çve- and six-membered carbo- and hetero-cyclic compounds. Not only are these reactions regio- and most often stereo-selective, but they are also entropically favoured. Palladium-catalysed cyclisation onto carbohydrate tem- plates2 o€ers a fast and e.cient route to chiral, highly func- tionalised polycyclic compounds that can be transformed into versatile synthetic intermediates.Recently, we described the Pd0-catalysed cyclisation of selected pseudoglycal 1,6- diene and 1,6-enyne derivatives for the synthesis of cis-annu- lated pyranoside products.3 We herein describe4 the for- mation of 5,6-bicyclic systems by palladium(0)-catalysed cyclisation of acetoxy-1,6-diene and 1,6-enyne C-glycoside derivatives.The catalysing properties of palladium were also exploited in the preparation of the starting material C-glyco- sides 3 and 7 (Scheme 2). `Metallo-ene type' cyclisation of 3 in acetic acid13 at 70 8C in the presence of a catalytic amount of Pd(PPh3)4 a€orded the cis-fused annulated C-glycoside derivative 4 as the sole product. The same product was obtained, in a somewhat reduced reaction time and in a slightly higher yield, when the isomeric C-glycoside 7 was subjected to similar reaction conditions. Although the precise mechanism for the cyclisation reac- tion is as yet unknown, it has been established that it pro- ceeds in a suprafacial manner, i.e. the alkene inserts predominantly into an intermediate p- (or s-)allylpalladium species, cis relative to the palladium atom.1 The observation that both the cis and trans substituted allyl acetate deriva- tives 3 and 7 gave the same cis annulated cyclisation pro- duct 4, analogous to observations made by Oppolzer,14 presumably implies a relatively slow trans¡¾cis isomerisation (Scheme 3) of the intermediate p-allylpalladium complex, allowing the palladium to be situated syn to the `enophile'.Additional useful functionality was incorporated into the molecule when the cyclised alkylpalladium intermediate was trapped1 with carbon monoxide instead of undergoing a b- elimination termination step. The trans disposed C-glycoside 7 was converted (Scheme 4) into the cyclised carboxylic acid product (isolated as the methyl carboxylate derivative 8) by Pd2(dba)3CHCl3/trio-o-tolylphosphine catalysis (dba= di- benzylideneacetone) in acetic acid at 46 8C in the presence of carbon monoxide (1 atm).Interestingly, similar treatment of 3 under prolonged reac- tion conditions produced only unreacted starting material (Scheme 4). This phenomenon can best be ascribed to a decrease in the electron density at the metal centre caused by the strong p-acceptor properties of the CO ligand, J.Chem. Research (S), 1998, 60¡¾61 J. Chem. Research (M), 1998, 0411¡¾0422 O OAc AcO AcO O OAc AcO OAc O OAc AcO CE2 i,ii iii E = CO2Et 1 2 3 O OAc O OAc AcO OAc O OAc AcO CE2 vi.viii iii 5 6 7 AcO OBut v O OAc H H E E 4 iv iv 1 2 3 4 5 6 7 8 9 Scheme 2 Reagents and conditions: i, water^1,4-dioxane, reflux; ii, Ac2O, py (1to 2; 93%); iii, diethyl allylmalonate, NaH, Pd(PPh3)4, THF (90%); iv, Pd(PPh3)4, HOAc,70 8C (83^89%); v,ButOH, BF3Et2O,THF (75%); vi, K2CO3,MeOH (99%); vii, PPh3, HOAc, DEAD,THF (93%); viii, Ac2O, ZnCl2, CH2Cl2Cl2, 0 8C (85%) O OAc CE2 Pd AcO L n O OAc CE2 Pd AcO L n Scheme 3 O OAc AcO CE2 E = CO2Et 3 O OAc AcO CE2 7 O OAc H H E E i i,ii H CO2Me 8 Scheme 4 Reagents and conditions: i, Pd2(dba)3CHCl3, tri-o-tolylphosphine, CO (1atm), HOAc, 46 8C; ii, CH2N2^diethyl ether, CH2Cl2, 0 8C (7 to 8; 80%) *To receive any correspondence. 60 J. CHEM. RESEARCH (S), 1998thereby suppressing p-allylpalladium complex formation.16 As a consequence, the rate of trans±cis isomerisation so dramatically decreased and only the trans substituted allyl acetate 7, which has favourable relative stereochemistry, undergoes cyclisation±carbonylation.Finally, cyclisation±carbonylation of the enyne 11 (Scheme 5) under the above reaction conditions proceeded faster17 with the alkyne `enophile', as compared to the alkene `enophile', to furnish 12, after diazomethane methyl- ation, in a high yield. In conclusion, we believe that this facile palladium cata- lysed preparation of chiral, functionalised 5,6-bicyclic sys- tems will be of value in the preparation of intermediates for the synthesis of polycyclic natural products.Furthermore, attention is drawn to the importance of paying due con- sideration to the relative stereochemistry of a precursor when planning and executing a palladium catalysed cyclisa- tion±carbonylation reaction. We are grateful to AECI (Ltd) and the Rand Afrikaans University for ®nancial support.Techniques used: NMR (1H, 13C and ROSY), ms, polarimetry Schemes: 5 References: 21 Received, 2nd September 1997; Accepted, 6th October 1997 Paper E/7/06399G References cited in this synopsis 1 Reviews: (a) W. Oppolzer, Pure Appl. Chem., 1990, 62, 1941; (b) W. Oppolzer, Angew. Chem., Int. Ed. Engl., 1989, 28, 38; (c) W. Oppolzer, In Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, vol. 5, p. 29. 2 Further examples include: (a) J.-F. Nguefack, V. Bolitt and D. Sinou, J. Org. Chem., 1997, 62, 1341; (b) J.-F. Nguefack, V. Bolitt and D. Sinou, Tetrahedron Lett., 1996, 37, 59. 3 C. W. Holzapfel, G. J. Engelbrecht, L. Marais and F. Toerien, Tetrahedron, 1997, 53, 3957. 4 Preliminary results on a part of this work: G. J. Engelbrecht and C. W. Holzapfel, Tetrahedron Lett., 1991, 32, 2161. 13 The acetic acid is thought to promote the reaction by protonation of the acetate ligand, thereby facilitating the formation of a cationic ( 3-allyl)palladium complex, a key inter- mediate in these reactions: E. Go mez-Bengoa, J. M. Cuerva, A. M. Echavarren and G. Martorell, Angew. Chem., Int. Ed. Engl., 1997, 36, 767. 14 (a) W. Oppolzer and J.-M. Gaudin, Helv. Chim. Acta, 1987, 70, 1477; (b) W. Oppolzer, Pure Appl. Chem., 1988, 60, 39. 16 L. S. Hegedus, Transition Metals in the Synthesis of Complex Organic Molecules, University Science Books, Mill Valley, USA, 1994, 23. 17 This observation has been previously made, see: W. Oppolzer and J. Ruiz-Montes, Helv. Chim. Acta, 1993, 76, 1266. O AcO AcO O AcO OAc O AcO CE2 i,ii iii E = CO2Et 9 10 11 O H H E E iv,v CO2Me 12 Scheme 5 Reagents and conditions: i, ButOH, I2,THF, reflux (70%); Ac2O, ZnCl2 (90%); iii, dimethyl prop-2-ymylmalonate, Pd(PPh3)4, NaH, THF (50%); iv, Pd2(dba)3CHCl3, tri-o-tolylphosphine, CO (1atm), HOAc, 46 8C; v, CH2N2-diethyl ether, CH2Cl2, 0 8C (11to 12, 65%) J. CHEM. RESEARCH (S), 1998 61

ISSN:0308-2342    

DOI:10.1039/a706399g

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Syntheses of Ferrocene Derivatives with Potentially Mesogenic Functional Substituents W. Edward Lindsell* and Lin Xinxin Department of Chemistry, Heriot-Watt University, Riccarton, Edinburgh EH14 4AS, UK Ferrocenyl imines, Fe{5-C5H4CH=NC6H4OCnH2n + 1-4)}(5-C5H5) and Fe{5-C5H3-1-(CO2Et)-3-(CH=NC6H4O- CnH2n + 1-4)}(5-C5H5) (n = 5^9) produced fromformylferrocene and1-(ethoxycarbonyl)-3-(formyl)ferrocene, respectively, and some diaryl esters of ferrocenedicarboxlic acids have been synthesised and characterised by analysis and spectroscopy. There is considerable interest in metal-containing liquid crystalline materials1 and a number of mesogenic com- pounds containing the ferrocene moiety has been made in recent years, including monofunctionalised, 1,3- and 1,1'- difuntionalised and trifunctionalised systems.3 We are inter- ested in developing mesogenic ferrocene entities with suit- able substituents for inclusion as side-chains in polymers.In this paper we report syntheses and characterisation of some precursor compounds.Various 1,3-ferrocene diesters with enantiotropic meso- phases have previously been prepared from ferrocene-1,3- dicarboxylic acid (1a), but the only reported route to the precursor diacid involves a lengthy set of sequential reac- tions from ethylferrocene.3,15 We have used a simpler, more versatile route to 1,3-disubstituted ferrocenes from (Z5- cyclopentadienyl)(Z6-p-xylene)iron(II) hexa�uorophosphate, easily prepared from unsubstituted ferrocene, and 2-(ethoxy- carbonyl)-6-(dimethylamino)pentafulvene, see Scheme 1.16 The initial product, following work-up by hydrolysis, is 1-(ethoxycarbonyl)-3-(formyl)ferrocene (2) and this can be used directly to form other 1,3-substituted derivatives by reactions at the aldehydic and/or ester functions.Alternatively, 2 is readily oxidised by silver(I) to ferrocene- 1,3-dicarboxylic acid (1a) from which 1,3-diesters and re- lated ferrocenes are preparable.Using 2 as a precursor, the new derivatives 10±14 were prepared. Also, for synthetic and spectroscopic comparisons, the imines 5±9 were obtained from formyl ferrocene. Moreover, we produced diester derivatives from 1a, includ- ing the previous uncharacterised species 3 and 4, and the re- lated 1,1'-isomers 15 and 16 from ferrocene-1,1'-dicarboxylic acid. The new compounds were characterised by analytical measurements and by IR, 1H and, in some cases, 13C NMR spectra. NMR resonances were assigned and include typical signals for the aromatic, imine and ester nuclei; e.g.[Fe{Z5- 1,3-C5H3(CO2Et)(CH=NC6H4OC5H11-4)}(Z5-C5H5)] (10) dH (CDCl3) 0.9 (br, 3 H, CH3), 1.4 (complex, 7 H, CH2 and CH3), 1.8 (m, 2 H, CH2), 3.95 (0t, 2 H, OCH2), 4.98, 5.07 and 5.40 (br, 3 H, H-2, -4, -5 of C5H3), 6.9 and 7.1 (AA'BB' m, 4, H, C6H4), 8.30 (s, 1 H, CH=N); dC (13C{1H}; CDCl3) 14.0 and 14.5 (CH3), 22.4, 28.2 and 29.0 (CH2), 60.4 and 68.3 (OCH2), 70.9 (C5H5), 70.7, 71.1 and 72.5 (CH, C-2, -4, -5 of C5H3), 74.0 (quat.-C, CCO2Et of C5H4), 83.8 (quat.-C, CCH=N of C5H4), 115.1 and 121.7 (arom.-CH), 145.2 (quat.arom.-C), 157.3 (CH=N), 157.6 (quat. arom.-C), 170.6 (CO). Visual observations of the thermal properties of the isolated compounds, using a hot-stage microscope, do not indicate well de®ned thermotropic mesogenic properties for most of the products, but attachment of an array of these entities as side chains to a functionalised polymer backbone by linking to the second substituent of a di-substituted ferrocene may generate liquid crystalline polymers.J. Chem. Research (S), 1998, 62±63 J. Chem. Research (M), 1998, 0423±0433 Fe CH 5–9 n = 5–9, respectively N OCnH2 n + 1 Fe X 15 X = CO2 CN 16 X = CO2 CO2 1b X = CO2H OMe X Fe+ PF6 – + NMe2 CO2Et Fe HO2C CO2H 1a Fe+ EtO2C CHO 2 Fe EtO2C HC 10–14 n = 5–9, respectively N OCnH2 n + 1 Fe ArO2C CO2Ar i,ii iii v vi iv 3 Ar = CN 4 Ar = OMe CO2 Scheme1 Reagents: i, h, ii,NaOHag^EtOH; iii, Ag2O^NaOH; iv, H2NC6H4OCnH2n + 1-4; v, (COCl)2; vi,HOAr *To receive any correspondence (e-mail: W.E.Lindsell@hw.ac.uk). 62 J. CHEM. RESEARCH (S), 1998L. X. thanks the Chinese Government for support. We also thank Professor J. M. G. Cowie, Heriot-Watt University, for helpful discussions. Techniques used: IR, 1H and 13C NMR, thermal polarising optical microscopy Tables: 1 (yields, melting points and analytical data for ferrocene derivatives) References: 23 Received, 13th August 1997; Accepted, 7th October 1997 Paper E/7/05941H References cited in this synopsis 1 E.g., see: S. A. Hudson and P. M. Maitlis, Chem. Rev., 1993, 93, 861; A.-M. Giroud-Goquin and P. M. Maitlis, Angew. Chem., Int. Ed. Engl., 1991, 30, 375; D. W. Bruce, J. Chem. Soc., Dalton Trans., 1993, 2983. 3 E.g., see: R. Deschenaux and J. W. Goodby, Ferrocenes, 1995, ed. A. Togni and T. Hayashi, VCH, Weinheim, ch. 9 and refer- ences cited therein. 15 (a) A. N. Nesmeyanov, E. V. Leonova, N. S. Kochetkova, A. I. Malkova and A. G. Makarovskaya, J. Organomet. Chem., 1975, 96, 275; (b) M. Hisatome, O. Tachikawa, M. Sasho and K. Yamakawa, J. Organomet. Chem., 1981, 217, C17; A. Kashara, T. Izumi, Y. Yoshida and I. Shimizu, Bull. Chem. Soc. Jpn., 1982, 55, 1901. 16 P. Bickert, B. Hildebrandt and K. Hafner, Organometallics, 1984, 3, 653. J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a705941h

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

3-(2-Alkoxy-1-hydroxyethyl)azetidin-2-ones: Potential Intermediates for the Synthesis of Novel Carbapenems Aisling C. O'Leary, Caroline M.Waldron, Catherine M. Burke, Raymond D. Keaveny and Mary J. Meegan* Department of Pharmaceutical Chemistry, School of Pharmacy,Trinity College, Dublin 2, Ireland 3-Vinyl and 3-isopropenylazetidin-2-ones can be transformed into the corresponding 3-(2-alkoxy-1-hydroxyethyl)azetidin-2- ones and 3-(1-alkoxy-2-hydroxypropan-2-yl)azetidin-2-ones by regioselective alcoholysis of 3-(1,2-epoxyethyl)azetidin-2-ones; 4-acetoxy-3-(1-hydroxy-2-methoxyethyl)-1-(4-methoxyphenyl)azetidin-2-one 14 is a synthetic precursor for carbapenems having both alcohol and alkoxyalcohol substituents at C-8.The 1-hydroxyethyl substituent at C-6 is a characteristic feature of many carbapenems isolated and synthesised to date and the presence of this group consistently demon- strates potent antibacterial activity e.g. thienamycin 1a, imipenem 1b and meropenem 2.1 Extensive carbapenem modiRcations have been reported, the vast majority of which involve the substituents at C-1 and C-2.2 However, Mastalerz et al.have reported a study on the synthesis and antibacterial activity of 6-aminoalkylcarbapenems4 and related compounds. Other C-6 modiRcations that have been investigated include 6-(1-�Puoroethyl),5 6-ethylidene,6 6-heteroethylidene7 and 6-[1-(hydroxymethyl)ethylidene] carbapenems (asparenomycins).8 The cholesterol absorption inhibition of 3-(2-aryloxy-1-hydroxyethyl)azetidin-2-ones has also been reported.9 The synthesis of a 4-acetoxy-3-(1-hydroxy-2-methoxy- ethyl)-1-(4-methoxyphenyl)azetidin-2-one 14 and related compounds is now described with a view to the introduction of alkoxyalkyl and related substituents at C-8 of carba- penems.We investigated the regioselective epoxide ring opening of 3-(1,2-epoxyethyl)azetidin-2-ones with alcohols and other oxygen nucleophiles under the mild and neutral conditions12,14,15 required for b-lactam chemistry.The required epoxides 5a�}f were obtained as illustrated in Scheme 1. The 3-vinyl-b-lactams 4a�}f were obtained by reaction of crotonyl chloride or 3,3-dimethylacryloyl chloride with the appropriate Schi€ bases 3a�}f. We have reported the use of 3-vinylazetidin-2-ones as intermediates in the synthesis of asparenomycin type carbapenem antibiotics10 while Manhas et al. have reported their use as intermediates for the PS series of carbapenems.11 The epoxides 5a�}f were prepared by oxidation of the 3-vinyl b-lactams 4a�}f with mCPBA and were obtained as diastereomeric mixtures.Treatment of the epoxides 5a�}f with methanol, ethanol or acetic acid with Woelm 200 neutral alumina12 was then carried out and the epoxides 5a�}f were opened regioselectively in each case to a€ord the corresponding b-alkoxyalcohols 6a�}h and related esters as diastereomeric mixtures. The trans nature of the b-lactam protons was maintained throughout the procedure.The regioselectivity of the process was evident from the 1H NMR spectrum. Diol 8 is produced in 25% yield from epoxide 5a together with required b-alkoxy alcohol 6a if conditions are not anhydrous. Oxidation of the b-alkoxy- alcohols 6a�}c to the corresponding carbonyl compounds 7a�}c with pyridinium chlorochromate provided conclusive proof of the regioselectivity of the alumina method for opening the 3-(1,2-epoxyethyl)azetidin-2-ones with alcohols.This procedure allowed the introduction of the alcohols methanol and ethanol at C-6 while the use of acetic acid as nucleophile allowed the introduction of an ester substituent of C-6. Regioselective methanolysis of 3-(1,2-epoxyethyl)-4- (4-methoxyphenyl)-1-phenylazetidin-2-one 5b by DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)14 was achieved giving rise to the corresponding b-methoxy alcohol 6b as a diastereomeric mixture in 49% yield. A similar alcoholysis reaction was carried out on b-lactam epoxides 5a, f using cerium ammonium nitrate (CAN) as the catalyst15 to a€ord the b-alkoxyalcohol products 6a, i, j, k.The alumina, CAN and DDQ methods are suitable for use in b-lactam chem- istry where mild neutral conditions are required to avoid unwanted reactions. In order to demonstrate the utility of the procedure for carbapenem synthesis we then examined the preparation of suitably modiRed 4-acetoxyazetidin-2-ones, well recognised as intermediates for carbapenem synthesis.19 This regio- selective alcoholysis of 3-(1,2-epoxyethyl)azetidin-2-ones was therefore applied to a 4-acetoxy substituted azetidin-2-one which would a€ord products which could be considered as precursors for carbapenems having the b-alkoxy alcohol type substituent at C-6.The 4-acetoxy-3-vinylazetidin-2-one 12 was obtained from the corresponding 4-formyl-3- vinylazetidin-2-one20 (Scheme 2) by oxidation to the car- boxylic acid followed by decarboxylation�}acetoxylation.10 Epoxidation of the vinyl compound 12 a€orded the epoxide product 13 as a diastereomeric mixture which was then reacted with methanol in the presence of alumina to a€ord the corresponding b-methoxy alcohol 14 as a diastereomeric mixture.A procedure for the synthesis of b-lactams containing a b-alkoxy alcohol type substituent at C-3 is described. This reaction gives access to b-lactam products which have the characteristic hydroxy group at C-5 of the side chain as found in clinically important carbapenems, and contain an additional alkoxyalkyl substituent at C-6.The development of this methodology for the stereoselective introduction of varied nucleophiles at C-9 of carbapenems is currently in progress. J. Chem. Research (S), 1998, 64�}65 J. Chem. Research (M), 1998, 0434�}0456 *To receive any correspondence. 64 J. CHEM. RESEARCH (S), 1998Scheme 1 Reagents and conditions: i, MeCH1CHCOCl or (Me)2C1CHCOCl, Et3N; ii, mCPBA; iii, R5OH, alumina, DDQ, or CAN; iv, pyridinium chlorochromate Scheme 2 Reagents and conditions: i, mCPBA, CH2Cl2; ii,MeOH, alumina We thank the Irish American Partnership and Forbairt for postgraduate scholarships (C.M.B., A.C.O'L and C.M.W).Techniques used: 1H and 13C NMR, IR, mass spectrometry, TLC Schemes: 2 Tables: 1 References: 23 Received, 24th July 1997; Accepted, 16th October 1997 Paper E/7/05350I References cited in this synopsis 1 R. Southgate, Contemp.Org. Synth., 1994, 1, 417. 2 J. Kant and D. G. Walker, in The Organic Chemistry of -Lactams, ed. G. I. Georg, VCH, New York, 1993, pp. 121± 196. 4 H. Mastalerz, M. Menard, E. Reudiger and J. Fung-Tomc, J. Med. Chem., 1992, 35, 953. 5 J. G. de Vries and G. Sigmund, Tetrahedron Lett., 1985, 26, 2765. 6 D. Habich and W. Hartwig, Tetrahedron Lett., 1987, 28, 781. 7 S. Coulton and I. Francois, J. Chem. Soc., Perkin Trans. 1, 1991, 2699. 8 K. Tanaka, J. Shoji, Y. Terui, N. Tsuji, E. Kondo, M. Mayama, Y. Kawamura, T. Hattori, K. Matsumoto and T. Yoshida, Antibiot., 1981, 34, 909. 9 M. P. Kirkup, R. Rizvi, B. B. Shankar, S. Dugar, J. W. Clader, S. W. McCombie, S. I. Lin, N. Yumibe, K. Huie, M. Van Heek, D. S. Compton, H. R. Davis and A. T. McPhail, Bioorg. Med. Chem. Lett., 1996, 6, 2069. 10 A. C. O'Leary, A. D. Neary, C. M. Waldron and M. J. Meegan, J. Chem. Res., 1996, (S) 368; (M) 2162. 11 M. S. Manhas, M. Ghosh and A. K. Bose, J. Org. Chem., 1990, 55, 575. 12 G. H. Posner and D. Z. Rogers, J. Am. Chem. Soc., 1977, 99, 8208. 14 N. Iranpoor and J. M. Baltork, Tetrahedron Lett., 1990, 31, 735. 15 N. Iranpoor and J. M. Baltork, Synth. Commun., 1990, 20, 789. 19 C. Palomo, in Recent Progress in the Chemical Synthesis of Antibiotics, ed. G. Lukacs and M. Ohno, Springer Verlag, Berlin, Heidelberg, 1990, p. 565. 20 B. Alcaide, Y. Martin-Cantalejo, J. Perez-Castell, J. Rodriguez- Lopez, M. A. Sierra, A. Monge and V. Perez-Garcia, J. Org. Chem., 1992, 57, 5921. J.

ISSN:0308-2342    

DOI:10.1039/a705350i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Kinetics and Mechanism of the Oxidation of Oxalic andFormic Acids by 2,2'-Bipyridinium ChlorochromateKavita Loonker, Pradeep K. Sharma and Kalyan K. Banerji*Department of Chemistry, J.N.V. University, Jodhpur 342 005, IndiaThe oxidation of formic and oxalic acids by 2,2'-bipyridiniumchlorochromate (BPCC) involves initial formation of an anhydride inter-mediate and its subsequent decomposition via a symmetrical cyclic transition state.2,2'-Bipyridinium chlorochromate has been used as a mildand selective oxidizing reagent.1 Here we report the kineticsof oxidation of oxalic acid (OA) and formic acid (FA) by2,2'-bipyridinium chlorochromate (BPCC) in dimethyl sulf-oxide (DMSO) as a solvent.The mechanistic aspects are dis-cussed. The oxidation of these acids by pyridinium uoro-,chloro- and bromo-chromates (PFC, PCC, PBC) have beenpreviously reported from this laboratory.6¡Ó8The reactions were studied under pseudo-rst-order con-ditions by keeping an excess (15 or greater) of the organicacid over BPCC.The solvent was DMSO, unless otherwisespecied. The reactions were followed by monitoring thedecrease in the concentration of BPCC at 365nm for up to80% reaction extent. Pseudo-rst-order rate constants, kobs,were evaluated from linear plots (r> 0.990) of log[BPCC]against time.The oxidation of organic acids by BPCC resulted in theformation of carbon dioxide. The overall reaction may,therefore, be written as eqns (1) and (2).COOH2 O2CrClO£¾bpyH£¾42CO2 2H2O OCrClO£¾bpyH 1HCOOH O2CrClO£¾bpyH£¾4CO2 H2O OCrClO£¾bpyH 2The reactions were found to be rst order with respect toBPCC.Michaelis¡ÓMenten type kinetics were observed withrespect to the organic acids. This leads to the postulation ofthe following overall mechanism [eqns (3) and (4)] and therate law (5).organic acid BPCC £¾£¾* )£¾£¾Kcomplex 3complex£¾4k2 products 4£¾dBPCC=dt k2KBPCC organic acid=1 Korganic acid 5The dependence on the concentration of the organic acidwas studied at dierent temperatures and the values of Kand k2 were calculated from the double reciprocal plots.Thethermodynamic parameters for the complex formation andthe activation parameters for the decomposition of thecomplex were calculated.To ascertain the importance of the cleavage of thea-CH bond in the rate-determining step, the oxidation ofa-deuterioformic acid (DCO2H) was studied. The resultsshowed that the formation constants of the formic acid¡ÓBPCC complex for ordinary and deuteriated acids do notdier much.The decomposition of the complex showedthe presence of a substantial primary kinetic isotope eect(kH/kD=5.77 at 303 K).The addition of acrylonitrile had no eect on the reactionrate. This indicates that a hydrogen abstraction mechanism,giving rise to free radicals, is unlikely.Solvent Eect.The oxidation of formic acid was studiedin 19 dierent solvents. There was no reaction with the sol-vents chosen and the kinetics were similar in all the solvents.It was observed that the formation constant, K, of the for-mic acid¡ÓBPCC complex does not vary much with the sol-vent but there is a considerable variation in the values of k2.The correlation of k2, in 18 solvents (CS2 was not con-sidered, as the complete range of solvent parameters wasnot available), in terms of the linear solvation energy re-lationship of Kamlet et al.10 is not signicant.The data on the solvent eect were analysed in terms ofSwain's equation12 of the cation- and anion-solvating con-cept of the solvents [eqn.(12)].log k2 aA bB C 12Here A represents the anion-solvating power of the sol-vent and B the cation-solvating power and C is the interceptterm. The rates of oxidation in the dierent solvents showan excellent correlation in terms of the Swain's equation[eqn. (12)], with cation-solvating power playing the majorrole.logK2 1:4320:04A 1:7220:03B £¾ 5:76R2 0:9970; sd 0:03; n 19 13The presence of a substantial kinetic isotope eectconrmed that an a-C0H bond is cleaved in the rate-determining step.The highly unfavourable entropy termobserved in the complex formation of the oxalic acid¡ÓBPCCJ. Chem. Research (S),1998, 66¡Ó67J. Chem. Research (M),1998, 0457¡Ó0471CO2HCO2H+OCrO¡VbpyH+O ClOCrO¡VbpyH+O ClC OC OO+ H2O(A)OCrO¡VbpyH+O ClC OC OOKk2 2 CO2 + CrOClO¡VbpyH+OH C OHOCrO¡VbpyH+O Cl+K OCrO¡VbpyH+HO ClC O O(B)HCrOClOO¡VbpyH+ OHC OHCO2 + H2O + CrOClO¡VbpyH+#Scheme 1 *To receive any correspondence.66 J.CHEM. RESEARCH (S), 1998reaction suggests that oxalic acid acts as a didentate ligand and forms a cyclic intermediate complex. In chromic acid oxidation also, the formation of a cyclic anhydride inter- mediate, oxalyl chromate, has been postulated.13 For the formic acid oxidation, the cation-solvating power of the solvents plays a relatively more important role. Therefore, formation of an electron-de¢çcient carbon centre in the transition state is indicated. Thus the decomposition of the BPCC¡¾formic acid complex may involve a hydride ion transfer via an anhydride intermediate (Scheme 1).However, there is no real evidence for a hydride-ion trans- fer. In a concerted cyclic process, the di€erence between proton, atom and hydride-ion transfer is very subtle and cannot be established experimentally. The large kinetic iso- tope e€ect simply shows that a hydrogen transfer is involved in the transition state.The involvement of a concerted cyclic process is supported by a study of the temperature dependence of the kinetic isotope e€ect. The data for protio- and deuterio-formic acids when ¢çtted in the familiar expression kH/kD=AH/AD exp(¢§DH*/RT) show a direct correspondence with the properties of a symmetrical transition state in which the di€erences in the activation energies for the protio and deuterio compounds are equal to the di€erences in the zero point energies of the corresponding C0H and C0D bonds (ca. 4.5 kJ mol¢§1) and the entropies of the activation of the respective reactions are almost equal.14,15 The reaction is catalysed by hydrogen ions. The hydrogen-ion dependence has the following form: kobs=a+ b[H+]. This suggests a reversible protonation of the anhydride with both the unprotonated and protonated forms being reactive. The protonated anhydride decomposes at a rate higher than the decomposition of the unprotonated anhydride (Scheme 2).Thanks are due to the University Grants Commission (India) and the Council of Scienti¢çc and Industrial Research (India) for ¢çnancial support. Techniques used: Spectrophotometry, correlation analysis References: 15 Equations: 16 Table 1: Rate constants for the oxidation of organic acids by BPCC in DMSO at 303K Table 2: Formation constants and thermodynamic parameters for the organic acid¡¾BPCC complexes in DMSO Table 3: Rate constants and activation parameters for the oxidation of organic acids by BPCC in DMSO Table 4: Dependence of the reaction rate on hydrogen ion concen- tration Table 5: Solvent e€ect on the oxidation of formic acid by BPCC at 303K Received, 29th July 1997; Accepted, 13th October 1997 Paper 7/05487D References cited in this synopsis 1 F.S. Guziec and F. A. Luzzio, Synthesis, 1980, 691. 6 R. Asopa, A. Mathur and K. K. Banerji, J. Chem. Res., 1992, (S) 152; (M) 1117. 7 S. Varshney, S. Kothari and K. K. Banerji, 1992, (S) 356; (M) 2901. 8 S. Rathore, P. K. Sharma and K. K. Banerji, J. Chem. Res. (S), 1994, 504. 10 M. J. Kamlet, J. L. M. Abboud, M. H. Abraham and R. W. Taft, J. Org. Chem., 1983, 48, 2877 and references cited therein. 12 C. G. Swain, M. S. Swain, A. L. Powell and S. Alumi, J. Am. Chem. Soc., 1983, 105, 502. 13 F. Hassan and J. Rocek, J. Am. Chem. Soc., 1972, 92, 9073. 14 H. Kwart and M. C. Latimer, J. Am. Chem. Soc., 1971, 93, 3770. 15 H. Kwart and J. H. Nickel, J. Am. Chem. Soc., 1973, 95, 3394. O Cr O.bpyH+ O Cl C O C O O H + (A) + H+ + 2 CO2 + HOCrClO.bpyH+ O Cr O.bpyH+ HO Cl C O OH + (B) + H+ H + CO2 + H2O + HOCrClO.bpyH+ Scheme 2 J. CHEM. RESEARCH (S), 1998 67

ISSN:0308-2342    

DOI:10.1039/a705487d

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Synthesis of Naturally Occurring (Z)-3- Benzylidenephthalide and (2) 3-Benzylphthalides{ Raghao S. Mali,* Archna P. Massey and Manohar I. Talele Garware Research Centre, Department of Chemistry, University of Pune, Pune 411007, India A convenient method, involving the generation of the phthalide anion, is described for the synthesis of naturally occurring (Z)-3- benzylidenephthalide (5) and (2) 3-benzylphthalides (6c, 10a^c), starting fromphthalides (7a and 7b). 3-Benzylidenephthalides are found to be synthetically useful intermediates for a wide variety of carbocyclic and hetero- cyclic compounds including some alkaloids.1 The (Z)-3-ben- zylidenephthalide (thunberginol-F 5),2 3-benzylphthalides3±5 (balantiolide 10a) and related phthalides (10b, 10c and 10e) and hydramacrophyllols A and B (6a and 6b) have been iso- lated from natural sources.These phthalides are valuable as they possess interesting biological activities. In view of the importance of 3-benzylidenephthalides, several general methods are reported for their synthesis.8 Since the iso- lation2 of thunberginol-F 5 in 1992, three methods have been reported for its synthesis.11±13 However, the naturally occurring 3-benzylphthalides 10a±c have not been syn- thesised so far.Since considerable work has been done in our laboratory on the synthesis of naturally occurring 3-alkylidenephtha- lides using the iodolactonisation approach, the approach was extended to the synthesis of 3-benzylidenephthalides15 (Scheme 1).The 3-benzylidenephthalides (3 and 4) were obtained in 13 and 12% yields respectively. The stereochem- istry of the 3-benzylidenephthalides (3 and 4) was deter- mined by 1H NMR. As the yields by this approach were poor, the syntheses of thunberginol-F 5 (2) 3-benzylphtha- lides 10a±c and the dimethyl ether 6c of hydramacrophyllols 6a and 6b have been achieved using the phthalide anion route (Scheme 2). For the synthesis of thunberginol-F, the anion of phtha- lide 7a,19 generated in situ18 using LDA in THF at ¡78 8C was treated with veratraldehyde.The hydroxyphthalide 8a was obtained as a mixture of diastereoisomers (1:1.6), in 55% yield. Dehydration of 8a using toluene-p-sulfonic acid in re—uxing benzene gave the trimethyl ether of thunbergi- nol-F, 9a, mp 186 8C (lit.,13 186±188 8C). The conversion of J. Chem. Research (S), 1998, 68±69 J. Chem. Research (M), 1998, 0472±0500 CO2H Ph O O Ph I H O O Ph H O O H Ph I2,aq KI, aq NaHCO3 NaOAc, EtOH reflux + 1 2 3 4 Scheme1 Scheme 2 O HO O H OH OH O OR O R2 OR 5 6a R = R1 = H, R2 = OH b R = R2 = H, R1 = OH c R = Me, R1 = OH, R2 = H 1 2 3 4 5 6 7 1c 2c 3c 4c 5c 6c H R1 $Dedicated to Professor M. S.Wadia on the occasion of his 60th birthday. *To receive any correspondence (e-mail: rsmali@chem.unipune. ernet.in). 68 J. CHEM. RESEARCH (S), 19989a to thunberginol-F 5 using BBr3 has already been reported in the literature.12,13 The syntheses of balantiolide 10a and related phthalides 10b and 10c have been achieved from phthalide 7b.The anion of 5,7-dimethoxyphthalide (7b) was reacted with veratraldehyde and 4-benzyloxy-3-methoxybenzaldehyde to obtain the hydroxyphthalides 8b and 8c. These phthalides 8b and 8c on dehydration using toluene-p-sulfonic acid gave the (Z)-3-benzylidenephthalides 9b and 9c which were hydrogenated, to give (2) O-methylbalantiolide (10b) and the (2) 3-benzylphthalide (10c) in 84 and 77% yields re- spectively.The naturally occurring 3-benzylphthalide, balantiolide (10a), has been synthesised from the benzylidenephthalide 9b via the intermediacy of 9e. The tetramethoxy 3-benzyl- idenephthalide 9b was reacted with AlCl3 in methylene chloride at room temperature, to give phthalide 9e in 82% yield. Hydrogenation of 9e using 10% Pd/C in ethyl acetate gave the (2) 3-benzylphthalide 10a in 71% yield. The 5,6-dimethoxyphthalide (7c)21 on similar sequence of reactions provided (2) 3-(4-methoxybenzyl)-5,6-dimethoxy- phthalide (10d), via the 3-hydroxyphthalide 8d and 3-benzyl- idenephthalide 9d.Using the phthalide anion approach the synthesis of 6c, a dimethyl ether of 6a and 6b, has been achieved in 73% yield from phthalide 7a. We are thankful to Professor N. S. Narasimhan for critical reading of the manuscript and valuable discussions. A.P.M. thanks the CSIR, New Delhi, for the award of a Senior Research Fellowship. M.I.T.thanks UGC New Delhi for the award of a teacher fellowship. Techniques used: IR, 1H NMR, elemental analysis, TLC and column chromatography References: 22 Schemes: 2 Received, 20th October 1997; Accepted, 22nd October 1997 Paper E/7/07565K References cited in this synopsis 1 (a) R. A. Aitken, H. R. Cooper and A. P. Mehrotra, J. Chem. Soc., Perkin Trans. 1 1996; 475; (b) Y. Masahisa, K. Kenshi, K. Takaki, A. Michitaka, K. Toshio and O. Nobuhiro, J. Med. Chem., 1993, 36, 4052; (c) T.Nishio, J. Chem. Soc., Perkin Trans. 1, 1995, 561; (d) E. Napolitano, R. Fiaschi, V. Scartoni and A. Marsili, J. Chem. Soc., Perkin, Trans. 1, 1986, 781. 2 M. Yoshikawa, E. Uchida, N. Chatani, N. Murakami and J. Yamahara, Chem. Pharm. Bull., 1992, 40, 3121. 3 L. Kraut, R. Mues and M. Sim Sim, Phytochemistry, 1994, 37, 1337. 4 Y. Asakawa, K. Takikawa, M. Tori and E. O. Campbell, Phytochemistry, 1986, 25, 2543. 5 (a) Y. Asakawa, K. Takikawa and M. Tori, Phytochemistry 1987, 26, 1023; (b) personal communication from Professor Asakawa. 8 (a) M. Noda, M. Yamaguchi, E. Ando, K. Takeda and K. Nokihara, J. Org. Chem., 1994, 59, 7968; (b) B. S. Joshi, Q. Jiang, T. Rho and S. W. Pelletier, J. Org. Chem., 1994, 59, 8220; (c) T. A. Crabb and A. Patel, J. Chem. Soc., Perkin Trans. 1, 1982, 2783; (d) N. E. Cundasawmy and D. B. MacLean, Can. J. Chem., 1972, 50, 3028; (e) T. Takada and S. Ohki, Chem. Pharm. Bull., 1971, 19, 977. 11 S. Ohta, Y. Kamata, T. Inagaki, Y. Masuda, S. Yamamoto, M. Yamashita and I. Kawasaki, Chem. Pharm. Bull., 1993, 41, 1188. 12 M. Yoshikawa, E. Harada, N. Yagi, Y. Okuno, O. Muraoka, H. Aoyama and N. Murakami, Chem. Pharm. Bull., 1994, 42, 721. 13 Zhi-Wei Wang, Shao-Bai Li and Yu-Lin Li, Indian J. Chem., 1996, 35B, 363. 15 M. I. Talele, M. Phil. Dissertation, University of Pune, 1986. 18 R. S. Mali, P. G. Jagtap, S. R. Patil and P. N. Pawar, J. Chem. Soc. Chem. Commun, 1992, 883. 19 R. S. Mali, P. G. Jagtap and S. G. Tilve, Synth. Commun, 1990, 20, 2641. 21 J. A. McRae, R. B. VanOrder, F. H. Gri�ths and T. E. Habgood, Can. J. Chem., 1951, 29, 482. J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a707565k

出版商:RSC    

年代:1998

数据来源: RSC