摘要:

N N N Ar 1 N N N Ar 2 CH2SiMe3 Tf – N N N Ar 3 CH2 – + N N N Ar 8 i N N N 10 NHAr 9 N N N Ar + N N N RO2C RO2C Ar H H –58.9 –239.0 61.5–62.0; 4.05–4.25 86–87 1 2 3 4 5 6 6a 7 8 9 10 10a 4 R = Me 5 R = Et N RO2C CO2 R NH CN Ar 125–127; 7.1 –200.9 –281.1 139.5–140.5 –135.3 heat ii + 6 R = Me 7 R = Et 428 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 428–429† Spiro-fused Tricyclic 7,8,9,10-Tetrahydro- 3H,5H-benzo[d]pyrrolo[1,2-c][1,2,3]triazoles and their Thermal Rearrangement to 1,3,4-Trisubstituted 2-(4-Cyanobutyl)pyrroles.Azolium 1,3-Dipoles† Richard N. Butler* and Denise C. Grogan Chemistry Department, University College Galway, Ireland New substituted tricyclic 7,8,9,10-tetrahydro-3H-5,H-benzo[d]pyrrolo[1,2-c][1,2,3]triazoles 4 and 5 rearrange on heating to afford high yields of 1-arylamino-2-(4-cyanobutyl)-3,4-bis(alkoxycarbonyl)pyrroles 6 and 7. Despite the range of known routes to the pyrrole ring system, 1 there is still a need to develop new routes to pyrroles with special substitution patterns2 because of the great importance of substituted pyrroles in natural products.3 Herein we describe a new route to 1,2,3,4-tetrasubstituted pyrroles 6 where the 2-substituent is a 4-cyanobutyl group.The precursor to these products is a new spiro-fused tricyclic benzo[d]pyrrolo[1,2-c][1,2,3]triazole ring system 4. We have recently4 established the efficacy of 1,2,3-triazolium- 1-(unsubstituted methanides) as 1,3-dipoles.Herein the tetrahydro-1,2,3-benzotriazolium-1-methanide series 3 has been generated in solution by in situ treatment of the unstable precursory trimethylsilyl methyl trifluoromethanesulfonate salts 2 with CsF following a literature5,6 desilylation process. When trapped with alkyne dipolarophiles, the dipoles 3 gave the new tricyclic products 4 and 5. These were isolated in moderate yields (Table 1) and were always accompanied by the side-products 9 and 10 formed by ring opening of 3 to afford the conjugated triazatriene species 8 from which compounds 9 and 10 arise via 1,6- and 1,5-electrocyclisations respectively.These side-products cannot be avoided and they are the only products when the species 2 are treated with CsF in the absence of an alkyne dipolarophile. The fused systems 4 and 5 proved to be efficient precursors for the special polysubstituted pyrrole systems 6 and 7. Thus heating of compounds 4 or 5 under reflux in toluene resulted in high-yield rearrangements to compounds 6 and 7 (Table).These were isolated as gums and purified by column chromatography. The driving force of the rearrangement is an aromatisation of the fused dihydropyrrole moiety of 4 and 5 to give the N-aminopyrrole structure in 6 and 7 as shown (Scheme 1). All of the compounds gave satisfactory microanalyses and the structures were established by IR and 1H, 13C and 15N NMR spectra. For compounds 4 and 5, the quaternary fused bridgehead C-10a appeared at dC 86–87 and the 3-CH2 saturated carbon appeared dC 61.5–62.The methylene hydrogens of the latter gave AB doublets at dH 4.05 and 4.25. In the aromatised products 6 and 7, these carbon signals were replaced by the pyrrole C-2 signal at dC 139.5–140.5 and the pyrrole 5-CH signal at dC 125–127 (dH 7.1). All of the other expected proton and carbon-13 NMR signals were observed. The carbon-13 assignments were supported by off-resonance decoupled spectra. Compound 4a showed 15N shifts for the doubly bound nitrogen at dN µ58.9 and for the singly bound N atoms at dN µ239, as expected,7 and the pyrrole 7a also showed the expected7 15N shifts (Scheme 1).The sideproducts 9 and 10 are standard products which arise unavoidably from ring-opening of 1,2,3-triazolium-1-methanide 1,3-dipole systems and we have listed their spectroscopic properties for other derivatives previously.8 The low-yield compounds 9 were oils while compounds 10 were solids.Experimental Mps were measured on an Electrothermal apparatus. Microanalyses were measured on a Perkin Elmer Model 240 CHN analyser. 1H and 13C NMR spectra were measured from internal Me4Si on a JEOL Lambda 400 MHz instrument with CDCl3 as solvent (J values in Hz). 15N shifts are from MeNO2. IR spectra were measured with a Perkin Elmer 983G spectrophotometer. The substrates 1 were prepared by procedures previously described.8,9 The following are typical examples. D i m e t h y l 5 - P h e n y l - 7 , 8 , 9 , 1 0 - t e t r a h y d r o - 3 H - 5 H - b e n z o [ d ] p y r r o l o - [1,2-c][1,2,3]triazole-1,2-dicarboxylate 4a.·A solution of 1a (0.5 g, 2.5 mmol) in trimethylsilylmethyltrifluoromethanesulfonate (0.75 cm3, 3.75 mmol) was stirred at 90 °C for 5 h, cooled to ambient temperatures, treated with dry CH2Cl2 (20 cm3) and dimethyl acetylenedicarboxylate (1.23 cm3, 10 mmol) followed by CsF (0.57 g, 3.75 mmol) and the mixture stirred at ambient temperature for 8 h and then filtered to remove salts.After the solvent had been removed under reduced pressure, the residue in CH2Cl2 (3 cm3) was placed on a silica gel-60 column (230–400 mesh ASTM) and eluted with a gradient of light petroleum (bp 40–60 °C)–Et2O *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). Scheme 1: a, Ar=Ph; b, Ar=p-BrC6H4; c, Ar=p-MeC6H4; d, Ar=p-MeOC6H4. Some key 1H and 13C shift ranges and 15N NMR shifts (for 4a and 7a) shown. Reagents: i, CsF; ii, RO2C�CO2RJ. CHEM. RESEARCH (S), 1997 429 (1:0–1:1 v/v) to give compound 4a (40%), mp 129–131 °C (from EtOH); vmax/cmµ1 (mull) 1724, 1736 (ester C�O); dH 1.9–2.0, 2.21–2.40, 2.52–2.54, 2.71–2.74 (multiplets, 8-H, cyclohexyl, four CH2); 3.75 and 3.91 (singlets, 3 H each, two CO2Me); 4.05, 4.25 (AB, doublets, J 17.3, 3-CH2); 7.0–7.04 (m, 2 H, Ph Hortho); 7.28–7.33 (m, 3 H, Ph Hmeta,para); dC 22.5, 25.9 (C-8, C-9); 26.1, 39.0 (C-10, C-7); 52.2, 52.8 (two MeO); 61.8 (3-CH2); 86.7 (C-10a); 148.2, 116.4, 128.7, 122.5 (5-N-Ph C-1p, C-2p, C-3p, C-4p respectively); 132.3, 142.9, 150.8 (C-1, C-2, C-6a); 162.3, 166.0 (ester C�O); dN µ58.9 (N-6); µ239.0 (N-4, N-5).Further elution with increasing portions of Et2O in the eluent recovered compounds 9a, (10%), 10a (25%) and 1a (5%) from the column.Dimethyl 1-Anilino-2-(4-cyanobutyl)pyrrole-3,4-dicarboxylate 6a. ·A solution of 4a (200 mg, 0.56 mmol) in dry tuluene (10 cm3) was stirred under reflux for 48 h, cooled, the solvent removed under reduced pressure and the residue in CH2Cl2 (3 cm3) placed on a silica gel-60 column (230–400 mesh, ASTM) and eluted with Et2O to give compound 6a as a low melting gum (85%): vmax/cmµ1 (mull) 3298 cmµ1 (NH), 1719 (br) (ester C�O), 2248 (C�N); dH 1.57, 2.20, 2.31, 2.76 (8 H, ms, four CH2); 3.76, 3.84 (s, 3 H each, two CO2Me); 6.49–6.51 (m, 2 H, Ph Hortho); 6.90 (m, 1 H, Ph Hpara); 7.15–7.24 (m, 2 H, Ph Hmeta); 7.1 (s, 1 H, pyrrole 5-CH); 7.7 (br, 1 H, NH); dC 16.0 (CH2·CN); 22.8, 24.3, 27.8 [(CH2)3] 51.1, 51.2 (two MeO); 110.9, 113.5 (C-3, C-4); 146.6, 112.5, 129.0, 121.3 (N-Ph C-1p, C-2p, C-3p, C-4p); 119.4 (C�N); 126.6 (pyrrole 5-CH); 140.0 (pyrrole C-2); 163.8, 164.8 (ester C�O).Received, 14th July 1997; Accepted, 5th August 1997 Paper E/7/05030E References 1 R.J. Sundberg, in Comprehensive Heterocyclic Chemistry II, ed. A. R. Katritzky, C. W. Rees and E. F. Scriven, Pergamon, Oxford, 1996, vol. 2, pp. 119–206 and references cited therein. 2 N. P. Pavri and M. L. Trudell, J. Org. Chem., 1997, 62, 2649. 3 D. M. Collard and M. A. Fox, J. Am. Chem. Soc., 1991, 113, 9415; C. P. Andrieux, P. Audebert, P. Hapiot and J. M. Saveant, J. Am. Chem. Soc., 1990, 112, 2439. 4 R. N. Butler, P. D. McDonald, P. McArdle and D.Cunningham, J. Chem. Soc., Perkin Trans. 1, 1996, 1617. 5 E. Vedejs, S. Larsen and F. G. West, J. Org. Chem., 1985, 50, 2170. 6 R.C. F. Jones, J. R. Nichols and M. T. Cox, Tetrahedron Lett., 1990, 31, 2333. psoborn and R. Muller, Angew. Chem., Int. Ed. Engl., 198, 25, 383. 8 R. N. Butler, J. P. Duffy, D. Cunningham, P. McArdle and L. A. Burke, J. Chem. Soc., Perkin Trans. 1, 1992, 147. 9 R. N. Butler, F. A. Lysaght, P. D. McDonald, C. S. Pyne, P. McArdle and D. Cunningham, J. Chem. Soc., Perkin Trans. 1, 1996, 1623; R.N. Butler, A. M. Gillan, S. Collier and J. P. James, J. Chem. Res. (S), 1987, 332. Table 1 Yields and physical and analytical data for products By-products Found (required) (%) 10 9 Cpd. (Mp T/°C) Yield (%) C H N Mp (T/°C) Yield (%) Yield (%) 4a 4b 4c 4d 5a 6a 6b 6c 6d 7a 129–131a 128–130a 130–132a 106–108a 79–81b —c —c —c —c —c 40 31 42 28 35 85 82 92 77 85 64.25 (64.2) 52.4 (52.5) 65.3 (65.0) 62.2 (62.3) 66.0 (65.8) 64.6 (64.2) 52.1 (52.5) 64.8 (65.0) 62.3 (62.3) 65.6 (65.8) 5.6 (5.9) 4.7 (4.6) 6.1 (6.3) 6.4 (6.0) 6.3 (6.5) 6.0 (5.9) 4.5 (4.6) 6.5 (6.3) 6.3 (6.0) 6.8 (6.5) 11.4 (11.8) 9.3 (9.7) 11.2 (11.4) 10.5 (10.9) 11.0 (11.0) 11.4 (11.8) 9.5 (9.7) 11.7 (11.4) 10.5 (10.9) 10.7 (11.0) 149–151 205–207 179–181 160–162 149–151 ————— 25 42 20 43 27 ————— 10 13 14 8 12 ————— aFrom EtOH. bFrom pentane. cLow-melting gum purified by column chromatography.

ISSN:0308-2342    

DOI:10.1039/a705030e

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

430 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 430–431† Environmentally Friendly Catalysis using Supported Reagents: Enhanced Selectivity without Loss in Activity in the Alkylation of Benzene using Hexagonal Mesoporous Silica (HMS)-supported Aluminium Chloride†,1 James H. Clark,*a Peter M. Price,a Keith Martin,b Duncan J. Macquarriea and Tony W. Bastockb aDepartment of Chemistry, University of York, Heslington, York YO1 5DD, UK bContract Catalysts Ltd., Knowsley Business Park, Prescot, Merseyside L34 9HY, UK Substantial increases in selectivity towards monoalkylation of benzene with alkenes can be achieved through the use of mesoporous HMS as support for immobilised aluminium chloride and through the use of external site poisons while maintaining activities comparable to homogeneous AlCl3.The selective monoalkylation of aromatics using alkenes is an important goal notably in the production of linear alkylbenzenes for the manufacture of detergents.2 Traditional homogeneous catalysts such as AlCl3 and HF give good rates of reaction but poor product selectivities.2,3 Their use also leads to health and safety, plant-corrosion and waste-disposal problems and is being phased out.Zeolites are solid acids that are safe to handle and can lead to much improved product selectivities but their activity, especially in reactions involving larger alkenes, is poor·the reaction of benzene with dodec-1-ene catalysed by HZSM-4, for example, is carried out at high temperatures and pressures.2 We recently reported the first example of an immobilised form of aluminium chloride which has an activity in alkylations comparable to that of AlCl3 itself but offers the advantages of a solid catalyst and is reusable.4 These supported reagents were based on broad pore-size-distribution silicas and acid-activated clays but still led to a small but significant improvement in selectivity towards monoalkylation.Further improvements in product selectivity are however extremely important, especially in these environmentally conscious days when waste minimisation is becoming a priority in many industries. 5 We now report that substantial improvements in selectivity towards monoalkylation can be achieved through the use of narrow pore-size-distribution hexagonal mesoporous silica (HMS).6 The catalyst shows significant improvements in selectivity in the alkylation of benzene using a range of alkenes (C6–C16) compared to both homogeneous aluminium chloride and aluminium chloride supported on acid-treated *To receive any correspondence (e-mail: jhc1@unix.york.ac.uk). †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 Comparison of reaction selectivities in the alkylation of benzene with various alkenes using supported aluminium chloridea Reaction Alkene time conversion Monoalkyl Polyalkyl Alkene Catalystb (t/h) (GC) (%) benzene benzenesc Oligomers Hex-1-ene Hex-1-ene Hex-1-ene Hex-1-ene Hex-1-ene Oct-1-ene Oct-1-ene Oct-1-ene Oct-1-ene Oct-1-ene Oct-1-ene Dodec-1-ene Dodec-1-ene Dodec-1-ene Dodec-1-ene Dodec-1-ene Dodec-1-ene Dodec-1-ene Dodec-1-ene Tetradec-1-ene Tetradec-1-ene Tetradec-1-ene Tetradec-1-ene Hexadec-1-ene Hexadec-1-ene Hexadec-1-ene Hexadec-1-ene Hexadec-1-ene AlCl3 K10–AlCl3 a HMS(24 Å)–AlCl3 HMS–AlCl3–Ph3N(1:5) HMS–Ph3SiCl–AlCl3 d AlCl3 K10–AlCl3 d SiO2(70 Å)–AlCl3 HMS(24 Å)–AlCl3 HMS–AlCl3–Ph3N(1:5) HMS–Ph3SICl–AlCl3 d AlCl3 K10–AlCl3 d HMS(24 Å)–AlCl3 HMS–AlCl3 e HMS–AlCl3–Ph3N(1:6) HMS–AlCl3 f HMS–Ph3SiCl–AlCl3 d HZSM-4g AlCl3 HMS(24 Å)–AlCl3 HMS–AlCl3–Ph3N(1:5) HMS–Ph3SiCl–AlCl3 d AlCl3 K10–AlCl3 d HMS(24 Å)–AlCl3 HMS–AlCl3–Ph3N(1:5) HMS–Ph3SiCl–AlCl3 d 0.5 2.5 0.5 0.5 0.5 0.5 2.0 1.25 0.5 0.5 0.5 0.5 2.0 0.5 1.0 0.5 0.5 0.5 ? 0.5 0.5 0.5 0.5 0.5 4.5 0.5 20.0 0.5 100 100 100 100 100 100 100 100 100 99.8 100 100 100 100 100 100 100 100 100 100 100 100 100 100 85.5 100 19.9 99.5 58.7 69.2 72.0 82.5 73.3 64.1 76.3 78.3 80.3 84.0 83.0 71.6 77.3 81.3 76.1 86.4 87.3 84.7 65.7 67.3 86.9 95.3 89.4 77.2 71.0 92.0i 14.4 95.1 41.3 30.8 28.0 17.5 26.7 35.9 23.7 21.7 19.7 15.8 17.0 28.4 21.3 18.7 23.8 13.6 12.7 15.3 ? 31.2 13.1 4.7 10.6 22.8 14.5 8.0 4.7 4.4 ——————————————————? ————————— aReactions were carried out at room temperature using 0.2 mol of benzene, 0.1 mol of alkene and 2 g catalyst (3 mmol with AlCl3 itself) under a nitrogen blanket, unless stated otherwise.bAll AlCl3 loadings=1.5 mmol gµ1, unless otherwise stated. cProducts heavier than dialkylates were only observed in the AlCl3 reactions. d0.75 mmol gµ1. eHMS left in a desiccator for 0.5 h before use. f0.05 mol alkene. gRef. 2; reaction carried out at 205 °C and 14 bar; 92% conversion after an unspecified time. hIsolated yields of product, iMinimum value: the starting material is only 92% pure and we were unable to purify it further: the % of non-monoalkylate=the original % impurity.J.CHEM. RESEARCH (S), 1997 431 clay K10 (Table 1). The selectivity of the catalyst is enhanced by using triphenylamine to poison external catalytic sites. The largest increase in selectivity, without significant loss in activity, was achieved at an AlCl3:Ph3N ratio of 1:5. Increases in selectivity were also observed when the HMS was pretreated with an excess of triphenylchlorosilane.This is presumably due to elimination of external hydroxy groups resulting in the aluminium chloride being supported within the pores of the HMS. Remarkably, for all the catalysts, activity remains high and is comparable with that of aluminium chloride (Fig. 1). For all alkylations, rearrangement of the alkene was observed resulting in the production of a variety of isomers for both the mono- and di-alkylated products.The monoalkylated isomers, identified by GC–MS, were due to the position of the phenyl group on the alkyl chain and are in close agreement with previous results;7 no branching of the alkyl chain was observed. The catalyst exhibited small improvements in selectivity towards the preferred 2-phenyl isomer.2,3 The results suggest that the increased selectivity of the catalyst is due to the alkylation taking place within the pores of the catalyst. The selectivity can be enhanced by poisoning any external catalytic sites with a bulky amine, or the removal of external hydroxy groups via the reaction with triphenylchlorosilane prior to catalyst preparation.Experimental GC–MS was carried out on a Varian 3400CX gas chromatograph with DB5 capillary column interfaced to a Finnigan Mat Magnum Mass Spectrometer. The 24 Å HMS support was prepared as described elsewhere.6 General Preparation of the Catalyst.·To sodium-dried benzene (0.2 mol) was added 2 g of support (dried at 300 °C for 18 h before use) and anhydrous aluminium chloride (3 mmol).The slurry was stirred at reflux for 1 h under dry nitrogen. Alkylation of Benzene.·To sodium-dried benzene (0.2 mol), containing the catalyst (2 g), was added the alkene (0.1 mol) over a period of 30 min, resulting in small exotherm (s10 °C). At 30 min intervals, small samples were taken from the reaction vessel and filtered to remove any catalyst. The products were identified by GC–MS.Poisoning of External Catalytic Sites.·To the catalyst (as previously prepared) was added triphenylamine (0.6 mmol) in benzene (1 ml). The mixture was stirred at room temperature for 30 min resulting in a blue-green catalyst. Modification of HMS.·To sodium-dried toluene (40 ml) was added 2 g of HMS (pre-dried at 300 °C for 18 h) and triphenylchlorosilane (0.06 mol). The mixture was stirred at reflux overnight under dry nitrogen. The resulting solid was filtered off, washed with acetone and dried on a rotary evaporator.We thank Contract Chemicals Ltd., EPSRC, the Royal Academy of Engineering (for a Fellowship to J. H. C.) and the Royal Society (for a University Research Fellowship to D. J. M.) for their financial support and other members of the EnvirocatsTM and York Clean Synthesis Groups for helpful discussions. Received, 26th June 1997; Accepted, 8th August 1997 Paper E/7/04509C References 1 J. H. Clark, P. M. Price, K. Martin and T. W. Bastock UK Pat. Appl., March 1997, P96302GB. 2 J. L. G. de Almeida, M. Dufaux, Y. Ben Taarit and C. Naccache, J. Am. Oil Chem. Soc., 1994, 71, 675. 3 S. Sivasanker and A. Thangaraj, J. Catal., 1992, 138, 386. 4 J. H. Clark, K. Martin, A. J. Teasdale and S. J. Barlow, Chem. Commun., 1995, 2037. 5 Chemisry of Waste Minimisation, ed. J. H. Clark, Chapman and Hall, London, 1995. 6 P. T. Tanev and T. J. Pinnavaia, Science, 1995, 267, 865. 7 R. D. Swisher, E. F. Kaelble and S. K. Liu, J. Org. Chem., 1962, 56, 4066. Fig. 1 Comparison of catalyst selectivities towards the monoalkylation of benzene using various alkenes

ISSN:0308-2342    

DOI:10.1039/a704509c

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

C NHR X COCHClR 1 O C C R Cl ZnCl2 RC NOH 3 28 20 R C N O + – N R C X ZnCl2 CO2Et NH2 11 CO2Et NH 12 CO 2 PhNCO ZnCl2 + CO2Et N(CONHPh)2 13 CO2Et NCONHPh2 14 + CO2Et 15 + N Ph HN O O + CO2Et NH2 16 CONHPh CO2Et NH2 11 CO2Et NHCOCH2Cl 23 ClCH2COCl–NEt3–CHCl3 CO2Et NH2 24 COCH2Cl + CO2Et NH 29 C Ph NOH PhClC NOH–Et3N ZnCl2 434 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 434 J. Chem. Research (M), 1997, 2434–2458 Reactions of Azulene and 2-Aminoazulene Derivatives with Isocyanates, Ketenes and Nitrile Oxides Noritaka Abe,*a Hiroshi Chijimatsu,a Satoru Kondo,b Hiroyuki Watanabeb and Katsuhiro Saito*b aDepartment of Chemistry, Faculty of Science, Yamaguchi University, Yamaguchi 753, Japan bDepartment of Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466, Japan Azulene reacted with heterocumulenes in the presence of Lewis acid to give 1-substituted azulenes whereas 2-aminoazulenes reacted with heterocumulenes to give 2-(substituted amino)azulenes together with 1-substituted azulenes.The cycloaddition of azulenes to reactive acetylenes gives a short and versatile access to heptalenes.3 With the expectation of novel cycloadditions and the formation of new azulene derivatives, we investigated the reactions of azulene and 2-aminoazulenes with heterocumulenes such as isocyanates, ketenes and nitrile oxides. The formation of some azulene derivatives and their properties are now reported.The reactions of azulene 1 with isocyanates, ketenes and nitrile oxides in the presence of Lewis acid occurred electrophilically at C-1 and gave azulene-1-carboxamides 3, 1-acylazulenes 20 and 1-aroylazulene oximes 28, respectively. Better yields were achieved in the reaction of 1 with isocyanates if the reactions were carried out without solvent and using zinc chloride as a Lewis acid. Reaction of 1 with chlorosulfonyl isocyanate in boiling xylene caused the cyanation of 1 at C-1 and C-3 as in the case of 1-azaazulenes7 and gave 3-chloroazulene-1-carbonitrile and azulene-1,3-dicarbonitrile. Reaction of ethyl 2-aminoazulene-1-carboxylate 11 with phenyl isocyanate occurred at C-1 and the amino group and gave rise to 1,3-bis(azulen-2-yl)urea 12, 3-(azulen- 2-yl)-1,5-diphenylbiuret 13, 1-(azulen-2-yl)-3-phenylurea 14, 1,2,3,4-tetrahydro-2,4-dioxo-1,3-diazabenz[a]azulene 15 and ethyl 2-amino-3-(N-phenylcarbamoyl)azulene-1-carboxylate 16.Chloroketene reacted with 11 at the amino group and C-3 to give the amide 23 and the acyl derivative 24.Phenyl nitrile oxide reacted with 11 at the amino group and gave ethyl 2 - { [ a- ( h y d r o x y i m i n o ) b e n z y l ] a m i n o } a z u l e n e - 1 - c a r b o x y l a t e 29. Techniques used: 1H and 13C NMR, IR, mass spectra References: 12 Schemes: 4 Table 1: The reactions of azulene 1 with isocyanates 2a–d Table 2: The reactions of azulene 1 with ketenes 19a–d Table 3: The reactions of azulene 1 with nitrile oxides 27a–e Received, 2nd June 1997; Accepted, 12th August 1997 Paper E/7/03817H References 3 K.Hafner, R. Diel and H. U. S�uss, Angew. Chem., 1976, 88, 121 (Angew. Chem., Int. Ed. Engl., 1976, 15, 104); K. Hafner, G. L. Knaup and H. J. Linden, Bull. Chem. Soc. Jpn., 1988, 61, 155 and references cited therein; W. Bernhard, H. R. Zumbrunnen and H.-J. Hansen, Chimia, 1979, 33, 324; W. Bernhard, P. Br�ugger, J. J. Daly, P. Sch�onholzer, R. W. Weber and H.-J. Hansen, Helv. Chim. Acta, 1985, 68, 415; W. Bernhard, P. Br�ugger, T. A. Jenny and H.-J. Hansen, Helv. Chim. Acta, 1985, 68, 429; Y. Chen, R. W. Kunz, P. Uebelhard, R. W. Weber and H.-J. Hansen, Helv. Chim. Acta, 1992, 75, 2447; P. Uebelhard and H.-J. Hansen, Helv. Chim. Acta, 1992, 75, 2493. 7 N. Abe, H. Matsuda, Y. Sugihara and A. Kakehi, J. Heterocyl. Chem., 1996, 33, 1323. *To receive any corresp

ISSN:0308-2342    

DOI:10.1039/a703817h

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Synthesis of Some Uridine and Cytidine Derivatives A. F. Sayed Ahmed Faculty of Science, Zagazig University, P.O. Box 322, Zagazig, Egypt Some modified nucleosides were prepared from 5,6-disubstituted uridine, 5-substituted cytidine and cytidine by nucleophilic substitution reactions in alkaline or neutral medium; preliminary antibacterial activities of the synthesized compounds have been measured. 5-(20-Thienyl) and (30-thienyl)cytosine derivatives were prepared as shown in Scheme 1.The iodination of cytosine then the trimethyl silylation reaction and the concentration with tributyl-2- and 3-thienyl ring were performed as before.15�}19 The coupling of both of the silylated derivatives, 5-(20-thienyl) and (30-thienyl)cytosine, with 1,2-di-O-acetyl- 3,5-di-O-benzoyl-b-D-ribofuranoside was carried out in N,N-dimethylformamide to give compounds 3 and 4 in high yield. The latter compounds were reacted with thionyl chloride in acetonitrile at 75 8C to give the chloro derivatives 5 and 6.Both 3 and 4 were converted into the corres- ponding 2'-azido compounds 7 and 8, respectively, by the reaction with diphenyl phosphorazidate, and diethyl azodi- carboxylate and triphenylphosphine, in THF. Advantage was taken of the facile formation of 6-azidouridine from uridine and of the ease with which the 6-azido group undergoes nucleophilic substitution to prepare 6-amino-5-hydroxymethyluridine (17) from 5-hydroxymethyl- uridine, and 6-amino-5-ethoxycarbonylmethyluridine (18) from 5-bromouridine.Mention should be made that compound 17 was prepared by reaction of 5-hydroxymethyluridine with sodium to form 5-hydroxymethyl-6-azidouridine (11) which was reacted with ammonia solution to give 6-amino-5-hydroxymethyl- aminouridine. The latter compound reacted with HCl in dioxane to give 17. On the other hand, compound 18 was prepared by the reaction of bromouridine with ethyl glycine ester. The resulting product reacted with sodium azide to give the 6-azido derivative which reacted with ammonium hydroxide solution to a€ord 18.Techniques used: IR, 1H NMR and mass spectrometry References: 21 Schemes: 2 Received, 9th March 1998; Accepted, 30th June 1998 Paper E/8/02182A References cited in this synopsis 15 D. Peters, A. B. HoE rnFeldt and S. J. Gronowitz, Heterocycl. Chem., 1991, 28, 1613. 16 K. A. Watanabe, T.-L. Su, R. S. Klein, C. K. Chu, A. Matsuda, M. W. Chun, C. Lopez and J. J. Fox, J. Med. Chem., 1983, 26, 152. 17 D. Peters, A-B. HoE rnfeldt, S. Gronowitz and N. G. Johansson, Nucleosides Nucleotides, 1992, 11, 115. 18 M. Krecmerova, H. Hrebabecky, M. Masojidkov and A. Holly, Collect. Czech. Chem. Commun., 1995, 61, 458. 19 A. Matsuda, J. Yasuoka, T. Sasaki and T. Ueda, J. Med. Chem., 1991, 34, 999. J. Chem. Research (S), 1998, 675 J. Chem. Research (M), 1998, 2880�}2894 Scheme 1 Scheme 2 J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a802182a

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Some Rearrangements of Gibberellins Catalysed by Tetracyanoethylene James R. Hanson* and Cavit Uyanik School of Chemistry, Physics and Environmental Science, University of Sussex, Brighton, Sussex BN1 9QJ, UK Tetracyanoethylene in methanol has been shown to catalyse the rearrangement of ring A of gibberellic acid to the 3 -methyl ether of gibberellenic acid and to the 19-2 -isolactone whilst the 13-hydroxygibberellin 16,17-epoxides are converted to 8:13-isogibberellins. Tetracyanoethylene has recently attracted interest as a mild p-acid catalyst for the methanolysis, cyclization and re- arrangement of epoxides.1�}6 The gibberellin plant hormones undergo a number of decomposition and rearrangement reactions in the presence of mineral acid.7 Under mildly acidic conditions at room temperature, gibberellic acid (1) a€ords gibberellenic acid (3) and allogibberic acid (5) whilst under more vigorous conditions a Wagner�}Meerwein re- arrangement of rings C and D takes place, leading to the formation of the 8:13-isogibberellins such as gibberic acid (7).8 This reaction, which is a characteristic of 13-hydroxy- gibberellins, has also been observed with 13-hydroxy-16,17- epoxides.11,12 Treatment of gibberellic acid (1) with tetracyanoethylene in methanol at 50 8C gave the 3b-monomethyl ether of gibberellenic acid 4 and the 19-2a-isolactone 9.Both com- pounds were identiRed by the characteristic position and multiplicity of the 1H NMR signals for their ring A protons. The 16a,17-epoxides 2,6 and 10 underwent rearrangement under the same conditions to a€ord the 17-hydroxy-8:13- isogibberellins 12 and 13, 8, and 11, respectively. These were identiRed primarily by the presence of the primary alcohol resonances in the 1H NMR spectrum and the cyclo- pentanone signal in the 13C NMR spectrum.Whilst the ring A epoxide of 10 was unchanged, ring A of 2 underwent rearrangement to form the 19-2a-isolactone. The methyl esters required for this work were prepared by methylation using methyl iodide and caesium �Puoride in dimethylformamide.16 This may be a less hazardous procedure for making gibberellin methyl esters than the conventional procedure using diazomethane.C.U. wishes to thank Kocaeli University, Izmit, Turkey, for study leave and Rnancial assistance. Techniques used: IR, 1H and 13C NMR References: 18 Table 1: 13C NMR data for 8:13-isogibberellins Received, 2nd June 1998; Accepted, 10th July 1998 Paper E/8/04144J References cited in this synopsis 1 Y.Masaki, T. Miura and M. Ochiai, Synlett, 1993, 847. 2 Y. Masaki, T. Miura and M. Ochiai, Bull. Chem. Soc. Jpn., 1996, 69, 195. 3 J. A. Boynton, J. R. Hanson and C. Uyanik, J. Chem. Res. (S), 1995, 334. 4 J. R. Hanson, P. B. Hitchcock and C. Uyanik. J. Chem. Res., 1998 (S) 300, (M) 1366. 5 I. G. Collado, J. R. Hanson and A. J. Macias-Sanchez, Tetrahedron, 1996, 52, 7961. 6 I. G. Collado, J. R. Hanson, R. Hernandez-Galan, P. B. Hitchcock, A. J. Macias-Sanchez and J. C. Racero, Tetrahedron, 1998, 54, 1615. 7 For a review see J. R. Hanson, Nat. Prod. Rep., 1990, 7, 41. 8 B. E. Cross, J. Chem. Soc., 1954, 4670. 11 K. Schreiber, G. Schneider and G. Sembdner, Tetrahedron, 1968, 24, 73. 12 A. G. Avent, M. K. Baynham, J. R. Hanson, P. B. Hitchcock and B. H. de Oliveira, J. Chem. Soc., Perkin Trans. 1, 1989, 627. 16 T. Sato, J. Otera and H. Nozaki, J. Org. Chem., 1992, 57, 2166. J. Chem. Research (S), 1998, 676 J. Chem. Research (M), 1998, 2850�}2861 *To receive any correspondence. 676 J. CHEM. RESEARCH (

ISSN:0308-2342    

DOI:10.1039/a804144j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Oxidative Addition of Tetraethylthiuram Disulfideto Tin(II) Catecholate: X-Ray and TheoreticalInvestigationsRadhakrishnan Selvaraju,a Parthasarathi Laavanya,aKrishnaswamy Panchanatheswaran,*a Lorenzo Pelleritob andG. La MannacaDepartment of Chemistry, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, IndiabDipartimento di Chimica Inorganica, Universita di Palermo, Via Archirafi 26, 90123 Palermo, ItalycDipartimento di Chimica Fisica, Universita di Palermo, Via Archirafi 26, 90123 Palermo, ItalyThe reaction of tin(II) catecholate with tetraethylthiuram disulfide yields the addition product(o-C6H4O2)Sn[S2CN(C2H5)2]2, whose structure has been elucidated by X-ray crystallography, as a rare neutral trischelate of tin(IV).The oxidative addition of several addenda to tin(II) cate-cholate is known.6 However, diphenyl disulde was reportednot to undergo oxidative addition with tin(II) catecholate.6This prompted us to investigate the reactivity of the lattertowards another disulde, viz.tetraethylthiuram disulde, amolecule capable of generating chelating dithiocarbamatefragments during oxidative addition. The results of ourinvestigation are presented below.A solution of TDS (3.64 mmol) in about 10 ml ofmethanol was added dropwise to a suspension of tin(II) cate-cholate (3.66 mmol) in methanol. The mixture was stirredfor about 15 h, whence a clear solution was obtained. Thesolvent was then removed in vacuo. The resulting orange¡Óred solid was washed with light petroleum (bp 40¡Ó60 8C)and dried under high vacuum.The product was solublein chloroform, benzene and tetrahydrofuran. Yield: 1.1 g;mp 231 8C(d). A perspective view of the molecule alongwith the atom numbering scheme is given in Fig. 1. Thetin atom has a distorted octahedral environment withtwo bidentate dithiocarbamato groups and one bidentatecatecholato group. The PM3 energy minimized structure22yielded bond lengths and angles which agreed well withthe experimental values.The thermodynamic stability of(o-C6H4O2)Sn[S2CN(C2H5)2]2 is revealed by its calculatedheat of formation (DHf=£¾30.97 kcal mol£¾1).Some details and results of the crystallographic study areas follows. Empirical formula, C16H24N2O2S4Sn; FormulaMr, 523.30; crystal colour/habit, orange¡Óred/plates; tem-perature, 298(2) K; wavelength, l 0.71069 A ; crystalsystem, triclinic; space group, P1; unit cell dimensions,a 9.759(1), b 10.391(4), c 13.199(1) A ; a 95.63(6),b 105.77(2), g 117.65(2)8; volume 1101(1) A 3; Z 2;Density (cald) 1.579 Mg m£¾3; absorption coecient 1.552 mm£¾1; F(000) 528; y range for data collection,2.29¡Ó24.988; index ranges 0EhE11, £¾12EkE10,£¾15ElE15; reections collected, 4116; independent reec-tions 3866 [Rint=0.0279]; renement method, full-matrixleast-squares on F2; data/restraints/parameters 3866/0/227;goodness-of-t on F2, 1.087; nal R indices [I>2s(I)],R1=0.0574, wR2=0.1974 (for 3474 data); R indices (alldata) R1=0.0637, wR2=0.2065; largest di.peak and hole1.565 and £¾1.793 e A £¾3, respectively; radiation, graphite-monochromated Mo-Ka; scan method, 2y. Additionalcrystal data can be found in the full text version.R.S. thanks the CSIR, Government of India, for nancialsupport in the form of SRF [CSIR award No. 9/475(44)93].K.P. thanks the UGC, New Delhi for research grants [F.12-108/90(RBB II) dt., 23.04.91] EMR-I].Techniques used: IR, 1H and 119Sn NMR, 119Sn Mo ssbauer, massspectrometry, single crystal X-ray diractionReferences: 22Table 1: Crystal data and renement parameters for(o-C6H4O2)Sn[S2CN(C2H5)2]2Table 2: Selected bond lengths and angles for(o-C6H4O2)Sn[S2CN(C2H5)2]2 by X-ray and PM3 calculationsReceived, 21st April 1998; Accepted, 24th July 1998Paper E/8/02982BReferences cited in this synopsis6 H.E. Mabrouk and D. G. Tuck, J. Chem. Soc., Dalton Trans.,1988, 2539.22 J. J. P. Stewart, MOPAC6.0, QCMP 137, QCPE, Bloomington,IN, USA.J. Chem. Research (S),1998, 677J. Chem. Research (M),1998, 2925¡Ó2945Fig. 1 Thermal ellipsoidal plot of (o-C6H4O2)Sn[S2CN(C2H5)2]2with 30% probability of thermal ellipsoids. Bond lengths (A )Sn¡ÓO(1) 2.033(5); Sn¡ÓO(2) 2.026(5); Sn¡ÓS(1) 2.541(3);Sn¡ÓS(2) 2.527(3); Sn¡ÓS(3) 2.548(2); Sn¡ÓS(4) 2.508(2). Bondangles (8) O(2)¡ÓSn¡ÓO(1) 81.3(2); S(2)¡ÓSn¡ÓS(1) 71.12(9);S(4)¡ÓSn¡ÓS(3) 71.40(9)*To receive any correspondence.J. CHEM. RESEARCH (S), 1998 677

ISSN:0308-2342    

DOI:10.1039/a802982b

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

The Regio- and Stereo-chemistries of the (2p á 2p) Photocycloaddition of Electron-deficient Ethenes to Isoquinolin-1(2H)-one Nader Al-Jalal,a Christopher Covellb and Andrew Gilbert*b aDepartment of Chemistry, Faculty of Science, Kuwait University, PO Box 5969, Safat, 13060 Kuwait bDepartment of Chemistry, The University of Reading, Whiteknights, PO Box 224, Reading, Berkshire, RG6 6AD UK The (2 á 2 ) photocycloaddition of isoquinolin-1(2H)-one to electron-deficient ethenes is efficient, regiospecific and highly stereoselective: 254 nm irradiation of the acrylonitrile adduct induces retroadditon and rearrangement to an N-vinylisoindolinone with equal efficiencies.Literature describing the (2p á 2p) photocycloaddition of ethenes to isoquinolinones is sparse but there does appear to be agreement that the reaction occurs with head-to- tail regioselectivity.4±10 These cyclobutane derivatives are reported to undergo photochemical cleavage using short- wavelength radiation to give either 2-ethenylbenzamides 1 or starting materials dependent on the adduct structure.10 We now report on the regio- and stereo-chemistries of the (2p á 2p) photocycloaddition reaction, and give the details of the photorearrangement of the cycloadduct 5 of isoquinolinon-1(2H)-one and acrylonitrile.The formation of the N-vinylisoindolinone 6 from 5 using 254 nm radiation11 transpires to be temperature dependent and only becomes a signi®cant process above 35 8C.At lower temperatures, a labile isomer is formed which has spectral data consistent with those of the ring-opened isomer 7: this then yields 6 by an intramolecular conjugate addition. The (2p á 2p) photoaddition arises from the triplet excited state of isoquinolin-1(2H)-one and is most favoured with electron-de®cient ethenes. The results for acrylonitrile derivatives as the addends are summarised in Table 1. Signi®cant features of these additions are (i) the regiospeci®- city derived from polar features in the addends, (ii) the high exo stereoselectivity of the cyano group and (iii) the pro- nounced selectivity for trans geometry of the cyano and alkyl or alkoxy substituents on the cyclobutane ring of the adducts regardless of the cis:trans ratio of the starting 3-substituted acrylonitriles.The dienophilic ethenes, methyl acrylate, methyl methacrylate and methyl vinyl ketone, also gave (2p á 2p) photoadducts with isoindolin-1(2H)-one with similar yields and selectivities to those observed for the acrylonitriles.Techniques used: 1H and 13C NMR, IR and mass spectrometry References: 16 Tables: 2 Received, 20th July 1998; Accepted, 21st July 1998 Paper E/8/05642K References cited in this synopsis 4 G. R. Evanega and D. L. Fabiny, Tetrahedron Lett., 1971, 1749. 5 T. Naito and C. Kaneko, Chem. Pharm. Bull., 1985, 33, 5328. 6 T. Naito and C. Kaneko, Tetrahedron Lett., 1981, 2671. 7 H. Suginome, Y. Kajizuka, M. Suzuki, H.Senboku and K. Kobayashi, Heterocycles, 1994, 37, 283. 8 T. Chiba, Y. Takada, T. Naito and C. Kaneko, Chem. Pharm. Bull., 1990, 38, 2335. 9 T. Chiba, Y. Takada, C. Kaneko, F. Kiuchi and Y. Tsuda, Chem. Pharm. Bull., 1990, 38, 3317. 10 C. Kaneko, N. Katagiri, K. Uchiyama and T. Yamada, Chem. Pharm. Bull., 1985, 33, 4160. 11 N. Al-Jalal, M. G. B. Drew and A. Gilbert, J. Chem. Soc., Perkin Trans. 1, 1996, 965. J. Chem. Research (S), 1998, 678 J. Chem. Research (M), 1998, 2912±2924 Table 1 The (2p á 2p) photocycloaddition of substituted acrylonitriles to isoquinolin-1(2H)-one Acrylonitrile derivative (2p á 2p) Cycloadducts Yield (%) Methacrylonitrile 16, 17a respective ratio 9:1 70b But-2-enenitrile (cis:trans ratio; 1:3)d 18, 19a respective ratio 9:1 35c Cis-pent-2-enenitrile 20 57b 3-Methoxyacrylonitrile (cis:trans ratio; 1:2)d 21e 75b 3-Ethoxyacrylonitrile (cis:trans ratio; 1:2)d 22 80b 2-Chloroacrylonitrile 23 45b aStructures tentatively assigned from 1H NMR spectra of enriched mixtures with its isomer.The yields of the adducts were not optimised and the values reported are those obtained following purification/separation by flash chromatographyb and two recrystallisations from methanolc at complete conversion of the isoquinolinone. dEstimated from 1H NMR spectroscopy. eMinor amounts (ca. 5%) of an unidentified 1:1 adduct isomer were also formed. *To receive any correspondence. 678 J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a805642k

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Ene-heterocyclic/Aromatic Schiff Bases as Potential Mesogens Claire Coutterez,a Alessandro Gandini,*a Giovanna Costab and Barbara Valentic aMate�Ê riaux Polyme! res, Ecole Franc�� aise de Papeterie et des Industries Graphiques (INPG), 38402 Saint Martin d'He! res, France bIstituto di Studi Chimico-Fisici di Macromolecole Sintetiche e Naturali, CNR, Via di Marini 6, 16149 Genova, Italy cDipartimento di Chimica e Chimica Industriale, Via Dodecaneso 31, 16146 Genova, Italy The condensation of aromatic mono- and di-amines with alkenyl furanic and/or thiophenic aldehydes gave a series of Schiff bases, some of which displayed liquid crystal properties.The recent synthesis of well-deRned conjugated oligomers bearing furan and/or thiophene heterocycles and a terminal aldehyde function,11 prompted us to investigate the possi- bility of using the latter reactive site to build structures possessing interesting properties. In the present context the speciRc feature sought was related to mesomorphicity and, therefore, applications related to the liquid crystal domain.The simple aldehyde/amine condensation was chosen for this study which involved, on the one hand, various dimeric alkenyl heterocyclic precursors and, on the other hand, several primary aromatic mono- and di-amines bearing di€erent substituents. The resulting Schi€ bases, obtained in high yields, had therefore the general structures shown below. Spectroscopic and elemental analyses conRrmed the validity of each expected structure.A thorough inspection of the thermal and morphological properties of all these compounds was then conducted using DSC and optical microscopy, both applied in successive heating�}cooling cycles. This enabled Rrst of all the assess- ment of the primary features related to the melting and crystallization and then a thorough search for mesophases. Only a limited number of structures displayed mesogenic properties. Among the monofunctional imines, only those bearing a thiophene ring attached to the CH.N moiety and, at the same time, a 4-cyano substituent (a well-known mesophase enhancer) on the aromatic ring showed the appearance of a nematic monotropic feature.The introduction of a methyl group at the C5 position of the outside heterocycle raised the mesophase stability and led to enantiotropic behaviour. Most of the Schi€ bases prepared with difunctional aromatic amines exhibited a clear-cut mesomorphism, but the high melting temperatures of some of them induced problems related to chemical stability.Techniques used: FTIR, 1H NMR, UV�}VIS, mass spectrometry, elemental analysis, DSC, optical microscopy References: 14 Fig. 1: Monotropic nematic texture of sample 7 at 86 8C Fig. 2: Enantiotropic nematic phase of sample 11 at 171 8C, on heating Fig. 3: DSC heating proRle of sample 11 Fig. 4: DSC heating proRle of sample 24 after cooling from the melt Table 1: Structures of the synthesized Schi€ bases Table 2: Thermal properties of the Schi€ bases resulting from the reaction with monofunctional amines Table 3: Thermal properties of the Schi€ bases resulting from the reaction with bifunctional amines Received, 7th July 1998; Accepted, 28th July 1998 Paper E/8/05254I References cited in this synopsis 11 C. Coutterez and A. Gandini, Polymer, 1998, 39, 7009. J. Chem. Research (S), 1998, 679 J. Chem. Research (M), 1998, 2966�}2987 Scheme 1 *To receive any correspondence. J. CHEM. RESEARCH (

ISSN:0308-2342    

DOI:10.1039/a805254i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Kinetic Evidence for the Mechanism of the Metal-substitution Reaction of Lead(II)-porphyrin with Cobalt(II) Rita Giovannetti,*a Vito Bartoccib and Giovanni Vitalib aCentro Interdip. Grandi Apparecchiature, Universita¢® di Camerino, 62032 Camerino, Italy bDipartimento di Scienze Chimiche, Universita¢® di Camerino, 62032 Camerino, Italy The catalytic effect of lead(II) in the reaction of 3,8,13,18-tetramethyl-21H,23H-porphine-2,7,12,17-tetrapropionic acid with cobalt(II) has been studied and the kinetic evidence is reported.Porphyrins have been extensively studied due to their very important role as complexing agents of metal ions; the general mechanism of metallation has been reviewed by several authors.4¡¾8 In this paper, we report a spectrophoto- metric study of the incorporation reaction of lead(II) and cobalt(II) into aqueous solutions of 3,8,13,18-tetramethyl- 21H,23H-porphine-2,7,12,17-tetrapropionic acid (CPI), in the temperature range 298¡¾321 K at pH 11.9 and an ionic strength of 0.28 mol L¢§1.The equilibrium (K) and kinetic (k1 and k¢§1) constants for the reaction PbII a CPI N PbII(CPI) (1) at 298 K were K a 5.820.1105 L mol¢§1, k1=79.020.1 L mol¢§1 s¢§1 and k¢§1=1.420.110¢§4 s¢§1. The reaction between cobalt(II) with CPI (CoII a CPI NCoII)(CPI) (5), is slower than reaction 1; its kinetic constant is k3=26.220.3 L mol¢§1 s¢§1, although the reaction may be accelerated by lead(II). This reaction, catalysed by lead(II) (3.5710¢§7 mol L¢§1) at ionic strength 0.28 mol L¢§1 and temperature of 298 K, occurs in two steps (Fig. 2); in the ¢çrst, PbII(CPI) is formed by reaction 1, while in the second CoII(CPI), according to the reaction PbII(CPI) a COII N CoII(CPI) a PbII (3), with k2=1.8820.04105 L mol¢§1 s¢§1.The kinetic par- ameters for reaction 1 are DH$=99.525.6 kJ mol¢§1 and DS$=133.621.4 J mol¢§1 K¢§1; for reaction 3: DH$= 6.720.7 kJ mol¢§1 and DS$=¢§ 113.020.2 J mol¢§1 K¢§1; and for reaction 5: DH$=51.220.9 kJ mol¢§1 and DS$= ¢§37.520.2 J mol¢§1 K¢§1.Techniques used: UV¡¾VIS References: 14 Table 1: Kinetic constants at di€erent temperatures Table 2: Activation parameters and Arrhenius constants for reactions 1, 3 and 5 at I a 0.28 mol L¢§1, 298 K Figure 1: Change in the spectrum (a) and in absorbance values (b) with time in the reaction between lead(II) (4.82010¢§5 mol L¢§1) and CPI (8.36610¢§6 mol L¢§1) at I a 0.28 mol L¢§1, 298 K Received, 27th April 1998; Accepted, 27th July 1998 Paper E/8/03146K References cited in this synopsis 4 D. K. Lavallee, Coord. Chem. Rev., 1985, 61, 55. 5 D. K. Lavallee, Comments Inorg. Chem., 1986, 155. 6 P. Hambright, in Porphyrins and Metalloporphyrins, ed. K. M. Smith, Elsevier, Amsterdam, 1975, pp. 232. 7 W. Schneider, Struct. Bonding, 1975, 23, 123. 8 M. Tanaka, Pure Appl. Chem., 1983, 55, 151. J. Chem. Research (S), 1998, 680 J. Chem. Research (M), 1998, 2958¡¾2965 Fig. 2 Change in the absorbance at 408 and 460 nm during the two-step reaction between cobalt(II) (7.59010¢§6 mol L¢§1) and CPI (1.55110¢§5 mol L¢§1) catalysed by lead(II) (3.57010¢§7 mol L¢§1), at ionic strength 0.28 mol L¢§1, 298 K *To receive any correspondence (e-mail: Giovannetti<bartocci@ camserv.unicam.it>). 680 J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a803146k

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Steroids Related to the Diterpenoid TumourInhibitor AphidicolinJames R. Hanson,* Peter B. Hitchcock and Cavit UyanikThe School of Chemistry, Physics and Environmental Science, The University of Sussex,Brighton, Sussex BN1 9QJ, UKThe syntheses of 2,17-dihydroxy-2-hydroxymethyl-A-nor-5-androstane, 3,17-dihydroxy-3-hydroxymethyl-5-androstane and 3,17-dihydroxy-3-hydroxymethyl-5,13-androstane are described, and the stereochemistry ofosmylation of a 3-methylene-5-androstane is established by X-ray crystallography.The diterpenoid fungal metabolite aphidicolin (1),1 which isa specic inhibitor of DNA polymerase a,2 has attractedinterest because it shows a potentially useful level of anti-tumour and antiviral activity.Structure¡Óactivity studies,which have been restricted by the availability of material,have revealed3¡Ó5 the importance of the distance between thering A and ring D hydroxy functions. This separation maybe mimicked on the readily available steroid skeleton.6Molecular models reveal that the superimposition of theC-17 hydroxy group of a steroid over the ring A C-18hydroxyl group of aphidicolin brings steroidal ring Aglycols, such as those based on C-3 of an androstane (2) orC-2 of an A-nor steroid (3), into juxtaposition with the ringD glycol of aphidicolin.The synthesis of the steroids 4, 5and 6 is described in this context.17b-Acetoxy-5a-androstan-3-one (7) was converted into17b-acetoxy-A-nor-5a-androstan-2-one (8),8 and thence bya Wittig reaction into 17b-acetoxy-2-methylene-A-nor-5a-androstane (9).The glycol 10 was obtained by reaction witha catalytic amount of osmium tetraoxide and potassiumhexacyanoferrate(III).9 Nuclear Overhauser enhancement stu-dies established the b-orientation of the hydroxymethylgroup. Hydrolysis of the 17b-acetate aorded the triol 4.A Wittig reaction with 17b-acetoxy-5a-androstan-3-one(7) gave the 3-methylene derivative 11,10 which was inturn osmylated and hydrolysed to form the glycol 5.Thestereochemistry at C-3 was established by an X-ray crystalstructure of the corresponding diacetate, 12 (Fig. 1). Theanalogous compound in the 13a-series was prepared via5a,13a-androstane-3,17-dione (13).12 The C-3 and C-17carbonyl groups diered suciently in steric hindrance fora selective Wittig reaction to generate the 3-methylenederivative 14. The glycol 6 was obtained from this bycatalytic osmylation and reduction at C-17.13The stereochemistry of osmylation of these alkenes hasled to the axial hydroxymethyl group with an equatorialtertiary alcohol.This may be rationalized in stereo-electronic terms in which the facial selectivity of reaction isfavoured by hyperconjugative interaction between the alkeneand the allylic axial C¡ÓH bonds.14Crystallographic Data and Structure Determination for 12.C24H38O5, Mr 406.5, monoclinic, space group P21 (no. 4),a 6.207(3), b 11.758(6), c 15.763(3) A , 908, 98.78(3)8, V 1136.9(8) A 3, Z 2, D 1.19 g cm£¾3,F(000) 444, monochromated Mo-K radiation, 0.71073 A , 0.08 mm£¾1 Data were collected for a crystalof size 0.200.200.05 mm on an Enraf Nonius CAD4diractometer.A total of 2290 reections were collectedfor 2<<258 and 0<h<7, 0<k<13, £¾18<l<18. Therewere 2103 independent reections and 946 reections withJ. Chem. Research (S),1998, 682¡Ó683J. Chem. Research (M),1998, 2862¡Ó2879*To receive any correspondence.682 J. CHEM.RESEARCH (S), 1998Fig. 1 X-Ray crystal structure of compound 12 I>2(I) which were used in the re®nement. There was no crystal decay and no absorption correction was applied. The structure was solved by direct methods using SHELXS-8615 and SHELXL-9316 for the structure re®nement. The non- hydrogen atoms were re®ned anisotropically by full-matrix least-squares. Hydrogen atoms were included in riding mode with Uiso=1.2Ueq(C) or 1.5Ueq(C) for methyl groups. The ®nal R indices were R1=0.0771, wR2=0.1705 and R indices (all data) R1=0.1863.wR2=0.2385. The goodness of ®t on F2 was 0.964 and the maximum shift/e.s.d. was 0.003. Tables of atomic coordinates and equivalent isotropic displacement parameters, bond lengths and angles, aniso- tropic displacement parameters, hydrogen atom coordinates and isotropic displacement parameters are given in the Appendix of the full-text paper. C.U. thanks the Kocaeli University, Izmit, Turkey for study leave and ®nancial assistance.Techniques used: 1H NMR, nOe, IR, X-ray crystallography References: 16 Appendix: Crystallographic data for 12 Received, 28th May 1998; Accepted, 2nd July 1998 Paper E/8/04002H References cited in this synopsis 1 W. Dalziel, B. Hesp, K. M. Stevenson and J. A. J. Jarvis, J. Chem. Soc., Perkin Trans. 1, 1973, 2841. 2 S. Ikegami, T. Taguchi and M. Ohashi, Nature (London), 1978, 275, 458. 3 S. Hiranuma, T. Shimizu, H. Yoshioka, K. Ono, H. Nakane and T. Takahashi, Chem. Pharm. Bull. Jpn., 1978, 35, 1641. 4 K. Ono, Y. Iwata and H. Nakane, Biomed. Pharmacother., 1983, 37, 27. 5 L. Arabshi, N. Brown, N. Khan and G. Wright, Nucleic Acid Res., 1988, 16, 5107. 6 J. A. Boynton and J. R. Hanson, J. Chem. Soc., Perkin Trans. 1, 1995, 2189. 8 T. Rull and G. Ourisson, Bull. Soc. Chim., Fr., 1958, 1573. 9 M. Minato, K. Yamamoto and J. Tsuji, J. Org. Chem., 1990, 55, 766. 10 J. Kalvado and H. Kaufman, J. Chem. Soc., Chem. Commun., 1976, 209. 12 J. R. Billeter and K. Miescher, Helv. Chim. Acta, 1951, 34, 2052. 13 T. Nambara, H. Hosoda and S. Goya, Chem. Pharm. Bull. Jpn., 1968, 16, 1266. 14 C. R. Johnson, B. D. Tait and A. S. Cieplak, J. Am. Chem. Soc., 1987, 109, 5875. 15 G. M. Sheldrick, in SHELXS-86 Program for the Solution of Crystal Structures, University of GoÈ ttingen, Germany, 1985. 16 G. M. Sheldrick, in SHELXL-93 Program for Crystal Structure Re®nement, University of GoÈ ttingen, Germany, 1993. J. CHEM. RESEARCH (S), 1998 683

ISSN:0308-2342    

DOI:10.1039/a804002h

出版商:RSC    

年代:1998

数据来源: RSC