摘要:

CH2 CH2 N N Me Me Me Me CH2 CH2 N N Me Me Me Me N N N Me Et N P N Me2N Me2N P NMe2 NMe2 NMe2 1 DMAMN 3 MTBD 2 DMAMB 4 P2Et J. CHEM. RESEARCH (S), 1997 151 J. Chem. Research (S), 1997, 151 J. Chem. Research (M), 1997, 1021–1040 Protonation of Very Strong Bases by Phenols in Nonaqueous Solutions Bogumil/ Brzezi�nski,a Eugeniusz Grech,b Zbigniew Malarski,c Maria Rospenk,c Grzegorz Schroedera and Lucjan Sobczyk*c aFaculty of Chemistry, A. Mickiewicz University, 60-780 Pozna�n, Poland bInstitute of Fundamental Chemistry, Technical University, 71-065 Szczecin, Poland cFaculty of Chemistry, University of Wrocl/aw, 50-383 Wrocl/aw, Poland The interactions between the very strong proton sponge bases 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) and Phosphazene Base, P2Et, and phenols of varying strength were studied in non-aqueous solutions using UV–VIS and IR spectroscopy.Whilst the interaction of proton sponges 1 and 2 with various proton donors has been the subject of numerous studies,8 there is little known about the complexation of very strong bases 3 and 4 in non-aqueous solvents.14 Consequently IR and UV–VIS studies of these bases with phenols were undertaken.Phenols can be considered as model proton donors15 as, by the introducing of various substituents, one can regulate their acidity over a broad pKa range. Their UV spectra are a sensitive indicator of the interaction strength and particularly of the degree of proton transfer.On the other hand, the IR spectra of the phenol complexes with bases provide important information on the features of hydrogen bonds formed between OH groups and the basic centres. 4-Methylphenol, 4-chlorophenol, 4-cyanophenol, 2,4,6-trichlorophenol and pentachlorophenol were used in CCl4, CHCl3, CH2Cl2 and MeCN. A variety of situations were found to be present depending on the solvent and phenol used. For weaker phenols in non-polar CCl4 complexation equilibria without proton transfer were observed whereas in the case of stronger phenols in MeCN complete complexation and the creation of strongly polar8 proton transfer states take place. Various intermediate states were found for medium strong phenols in weakly polar solvents.In many cases the ion pairs are characterized by extended charge separation. The UV band shifts upwards very long wave lengths, Fig. 1. The IR spectra reflect the complicated situation which appears in the intermediate states, Fig. 2. For 1:1 complexes only a weak band assigned to the ‘free’ N+–H group occurs which is characteristic of a tetrachloroaureate salt and a ‘continuum’ characteristic of hydrogen bridges with double minimum or with a broad asymmetrical single minimum potential. 18 For the 2:1 complexes the intensity of the continuum reaches high values that correspond to the formation of (OHO)µ bridges. Simultaneously the intensity of the +N–H bands indicates a full proton transfer to the MTBD molecule.The financial support from the Committee for Scientific Research (KBN grant 3 T09A 059 10) is acknowledged. Techniques used: IR, UV–VIS References: 31 Table 1: pKa values of N-bases in acetonitrile Table 2: Complexation and proton transfer equilibrium constants for systems phenols-strong bases in various solvents with positions of phenolic band in the UV region Figs. 1–9: UV and IR spectra of various phenol-N-base systems in non-aqueous solvents Received, 8th November 1996; Accepted, 22nd January 1997 Paper E/6/07619J References cited in this synopsis 8 B.Brzezi�nski, A. Jarczewski, J. Olejnik and G. Schroeder, J. Chem. Soc., Perkin Trans. 2, 1992, 2257; G. Schroeder, B. Brzezi �nski and A. Jarczewski, J. Mol. Struct., 1992, 274, 83; G. Schroeder, B. Brzezi�nski, Z. Malarski and L. Sobczyk, Pol. J. Chem., 1994, 68, 261. 14 B. Brzezi�nski, P. Radzijewski and G. Zundel, J. Chem. Soc., Faraday Trans., 1995, 91, 3141. 15 Th. Zeegers-Huyskens and P. Huyskens, Proton Transfer and Ion Transfer Complexes in Molecular Interactions, eds. H. Ratajczak and W. J. Orville-Thomas, Wiley, New York, 1980, vol. 2. 18 G. Zundel, Trends Phys. Chem., 1992, 3, 129. *To receive any correspondence. Fig. 1 UV spectra of 2,4,6-trichlorophenol–MTBD systems in MeCN: (1) phenol; (2) 1:1 system; (3) phenol in CCl4 with added KOH in ethanol; (4) phenol in water with KOH Fig. 2 IR spectra of 4-cyanophenol–MTBD systems in MeCN: (1) 1:1 system; (2) 2:1 system; (3) MTBD.HAuCl4 salt

ISSN:0308-2342    

DOI:10.1039/a607619j

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

MeO MeO O NMe MeO MeO NO2 O MeO MeO NH2 O O NCOR O MeO MeO NHCOR O MeO NCOR O O OH MeO MeO NCOR O 19 2 OH 19 1 O R¢O O 7 5 NMe 8 9 O R¢O O 17 NMe 1 2 3 9 14 10 4 NH NH CH2R 4 7 i R O ii iii O MeO viii vii NMe iv 5 vi O N 8 6 O R iv v,iv 10 Me Ph PhCH2CH2 PhCH2O PhCH2 PhCH2CH2CH2 CH3[CH2]4 a b c d e f g R HO ix O NH O MeO O N O R O R Me 11 + 8 4 MeO O N O R H OH MeO O N O OH O O N OH 18 R O R Me 12 + 7 + 152 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 152–153 J. Chem.Research (M), 1997, 1001–1020 Short Synthesis of 14b-Acylaminocodeinones from the Cycloadducts of Thebaine and Acylnitroso Compounds Ross I. Gourlay and Gordon W. Kirby* Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK Thebaine 1 has been converted in four steps, via its cycloadducts 7 with acylnitroso compounds and the derived dimethyl ketals 8 or ethylene ketals 13, into 14b-acylaminocodeinones 5 (Rp=Me), analgesics formerly prepared from 14b-aminocodeinone dimethyl ketal 3. 14b-Aminocodeinone dimethyl ketal 3, originally prepared2 from thebaine 1 via the nitro ketal 2, was a key intermediate in the synthesis of the acylamino- 5 (Rp=Me) and alkylamino- codeinones 6 (Rp=Me) (Scheme 1).1 These codeinones and the corresponding morphinones (Rp=H) have shown promise as clinically useful analgesics. For example, 14b-pentylaminomorphinone, pentamorphone 6 (R=Bu, Rp=H), has been evaluated3 in man and identified as an effective analgesic with clinically tolerable side-effects in the dose range 0.12–0.24 mg kgµ1.In the mouse hot-plate test, pentamorphone showed4 1872 times the potency of morphine and 4 times that of fentanyl. Since the compounds having substantial analgesic potency are all N-acyl (5) or N-alkyl (6) derivatives of the parent aminocodeinone, we have now devised a synthetic route from thebaine 1 in which the required acyl groups are introduced directly in the first step and which avoids nitration with tetranitromethane and the consequent formation of potentially hazardous salts of trinitromethane. Thebaine 1 reacts with transient acylnitroso compounds, RCONO, generated in situ by oxidation of hydroxamic acids, RCONHOH, with periodate, to give the cycloadducts 7 in high yield.7 In principle, a general synthesis of the acylamino ketals 4 might then be completed in two, unremarkable steps, viz.methanolysis of the cyclic ketals 7 and deoxygenation of the resulting hydroxamic acids 8.The 3-phenylpropanoyl cycloadduct 7c was selected initially for detailed study since the corresponding codeinones 5c (Rp=Me) and 6c (Rp=Me) and morphinones (Rp=H) were especially potent analgesics. Brief treatment of the cycloadduct 7c with dry, methanolic hydrogen chloride at 0 °C gave the dimethyl ketal 8c in good yield. However, attempted deoxygenation of the hydroxamic acid 8c with standard reagents was uniformally unsatisfactory. For example, zinc in acetic acid, or acetic acid alone, simply regenerated the cycloadduct 7c, while zinc and ammonium acetate caused no significant change.Other, more powerful reducing agents caused reductive removal of the entire 14-acylamino group. However, phosphorus trichloride in pyridine10 at 10 °C rapidly gave, in high yield, the required amide 4c, which was hydrolysed with methanolic hydrochloric acid to afford the codeinone 5c (Rp=Me). Other transformations of the cycloadduct 7c gave successively the hydroxamic acid 9c and the bridged phenol 10c (Scheme 1)7 and the oxazolidine 12c (Scheme 3).Unexpectedly, a serious limitation of this route to the dimethyl ketals 4 became apparent when other cycloadducts 7 were investigated. Although methanolysis of the 3-phenylpropanoyl derivative 7c was essentially quantitative, incomplete conversion was observed for all the other cycloadducts tested. The approximate positions of the equilibria 7M8, determined from the 1H NMR spectra of the reaction mixtures, are expressed, as follows, as % conversions into the ketals 8: 8a, 85%; 8b, 63; 8c, a95; 8d, 50; 8e, 90; 8f, 60; 8g, 70.Since methanol was already employed in a large excess as the solvent, there was no means of displacing the ketal equilibria substantially in the forward direction. Attention was there- Scheme 1 Reagents and conditions: i, C(NO2)4 in MeOH–NH3; ii, Zn–NH4Cl in MeOH; iii, RCOCl–pyridine; iv, HCl–H2O; v, B2H6–THF or LiAlH4; vi, RCONHOH–NaIO4; vii, dry MeOH–HCl; viii, PCl3–pyridine at 10 °C; ix, NaOEt–EtOH at 20 °C Scheme 2 Reagents and conditions: SO2 in pyridine at 115 °C Scheme 3 Reagent: NaBH3CN–HCl in dry THF *To receive any correspondence.O O O NCOR OH O 14 O O NHCOR 13 7 5 i ii iii J.CHEM. RESEARCH (S), 1997 153 fore turned to the thermodynamically more stable, cyclic, ethylene ketals 13 (Scheme 4).6 Treatment of the cycloadduct 7c in dichloromethane with an excess of anhydrous, glycolic hydrogen chloride at room temperature effected essentially quantitative formation of the ethylene ketal 13c.Significantly, the benzoyl cycloadduct 7b, which gave only ca. 63% of the dimethyl ketal 8b, also underwent essentially complete conversion into the ethylene ketal 13b. Although the ketals 13 were deoxygenated effectively with phosphorus trichloride in pyridine, an alternative method,13 which gave cleaner products, was devised. Thus, solutions of the ethylene ketals 13 in pyridine were saturated at room temperature with sulfur dioxide then heated under reflux, to afford the amides 14 in good yield.When this method was applied to the dimethyl ketal 8c, concomitant deoxygenation and cyclisation gave the oxazoline 11c (Scheme 2). Finally, hydrolysis of the ethylene ketals 14 with hydrochloric acid gave the acylaminocodeinones 5 (Rp=Me). In conclusion, the route (Scheme 4) involving deoxygenation of the ethylene ketals 13 with sulfur dioxide in pyridine is recommended generally for the conversion of thebaine, in four steps, into 14b-acylaminocodeinones.No chromatographic purifications are necessary and yields of 70–80% per step are usual. The route (Scheme 1) employing deoxygenation of the dimethyl ketals 8 with phosphorus trichloride in pyridine was satisfactory only for the cycloadducts 7a, c and e; with the other derivatives the equilibration 7M8 reduced the overall yield. We thank the SERC for financial support, Reckitt and Colman Pharmaceutical Division for pharmacological tests and their interest in this work and Dr J.W. Lewis for helpful discussions. Techniques used: IR, 1H NMR, mass spectrometry References: 14 Schemes: 4 Received, 23rd December 1996; Accepted, 22nd January 1997 Paper E/6/08557A References cited in this synopsis 1 R. J. Kobylecki, I. G. Guest, J. W. Lewis and G. W. Kirby, DTOLS 2,812,580, 1978 (Chem. Abstr., 1979, 90, 87709t); DTOLS 2,812,581, 1978 (Chem. Abstr., 1979, 90, 39100r); see also J. W. Lewis, C. F. C. Smith, P. S. McCarthy, D. S. Walter, R. J. Kobylecki, M. Myers, A. S. Haynes, C. J. Lewis and K. Waltham, NIDA Res. Monogr. Ser., 1988, 90, 136. 2 R. M. Allen, G. W. Kirby and D. J. McDougall, J. Chem. Soc., Perkin Trans. 1, 1981, 1143; see also C. F. Henderson, G. W. Kirby and J. Edmiston, J. Chem. Soc., Perkin Trans. 1, 1994, 295. 3 P. S. A. Glass, E. M. Camporesi, D. Shafron, T. Quill and J. G. Reves, Anesth. Analg. (N.Y.), 1989, 68, 302. 4 F. G. Rudo, R. L. Wynn, M. Ossipov, R. D. Ford, B. A. Kutcher, A. Carter and T. C. Spaulding, Anesth. Analg. (N.Y.), 1989, 69, 450. 6 G. W. Kirby and D. McLean, J. Chem. Soc., Perkin Trans. 1, 1985, 1443. 7 G. W. Kirby and J. G. Sweeny, J. Chem. Soc., Perkin Trans. 1, 1981, 3250. 10 E. Ochiai, J. Org. Chem., 1953, 18, 534. 13 Cf. G. W. Kirby, H. McGuigan and D. McLean, J. Chem. Soc., Perkin Trans. 1, 1985, 1961. Scheme 4 Reagents and conditions: i, dry (CH2OH)2–HCl at 20 °C; ii, SO2 in pyridine at 115 °C; iii, HCl–H2O–MeOH

ISSN:0308-2342    

DOI:10.1039/a608557a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N N NH N X Me N NNH2 O Me N NNHCXR O Me N N N O Me N S O Ph O N N O N NPh S O N O O Me N N N N R Me N N Me N N N Ar Me (2n) O O O O O O O O O O O S S Me Ph C6H4NO2-m C6H4NO2- p C6H4OMe- p C6H4Cl- p NH2 NHC6H4NO2-m NHC6H4OMe- p NH2 NHPh a b c d e f g h i j k l n R = CH CHPh 2 X NH 8a 8b R X = O 11 CH CHPh 9 6 NH CH CHPh 7 1 10 N NNHCOCH2Cl O Me CH2(CO2H)2 2 (2h, 2l) Heat H2NCXNH2 (2b) CH3CO2 – NH4 + H2NNHCSNH2 N NNHSO2C6H4Me- p O Me RCXY NaOEt –HY –H2O H+ H2NCMe X = S N N NH R O 2m ClCOCH2Cl 2o ClSO2C6H4Me- p (2g) NaOEt (2a-g) –H2O, 3a-g J.Chem. Research (S), 1997, 154–155 J. Chem. Research (M), 1997, 1041–1063 Synthesis and Biological Evaluation of Some New Fused Quinazoline Derivatives Salah S. Ibrahim, Ali M. Abdel-Halim, Yassien Gabr, Soummaia El-Edfawy and Reda M. Abdel-Rahman* Department of Chemistry, Faculty of Education, Ain-Shams University, Roxy, Cairo, Egypt We report that biologically active fused quinazolines have been synthesized via treatment of 3-(N-acyl/ aroylamino)quinazolin-4(3H)-ones (2) with various nucleophilic reagents; some of the products showed moderate antibacterial activity.The present work describes the synthesis of some new fused quinazolines starting from 3-(N-acyl/aroylamino)-2-methylquinazolin- 4(3H)-ones11 (2) and their antimicrobial activity in order to establish a relation between structure and reactivity. 2-Substituted pyrazolo[5,1-b]quinazolin-9(1H)-ones (3a–g) were obtained by refluxing 2 with sodium ethoxide (Scheme IA).Acylation of 3e followed by treatment with ammonium acetate–acetic acid13 afforded the heterocyclic system 5 (Scheme II). Also, 2-cinnamyl-5-methyl-s-triazolo[2,3-c]quinazoline (6) and 4-(4-chlorophenyl)-2,7-dimethyl[1,2,4,6]tetrazepino[ 2,3-c]quinazoline (7) were isolated from refluxing 2b with ammonium acetate–acetic acid and 2g with acetamidine hydrochloride in sodium ethoxide14 respectively. Investigations of the structure–activity relationships of 2h and 2l indicated that their activities are increased by fusion above their melting points to give 2-hydroxy/sulfanyl- 5-methyl-s-triazolo[1,5-c]quinazolines (8a,b).Interestingly, it was found that 2n on reaction with malonic acid in acetyl chloride15 produced 1-(2-methyl-4-oxoquinazolin-3-yl)-3 p h e n y l - 2 , 3 - d i - h y d r o - 2 - t h i o x o p y r i m i d i n e - 4 , 6 ( 1 H, 5H ) - d i o n e (10) which on refluxing with sodium ethoxide gave the pyrimido[ 3p,4p: 2,3]pyrazolo[5,1-b]quinazolinedione 11.The IR spectrum of 11 showed characteristic absorption bands at vmax 3194 (OH), 1692 (C�O), 2923 (CH2, CH3), 1316 (NCS) and 1109 cmµ1 (C·S). The mass spectrum of 11 showed loss of Ph and H2 to give a base peak at m/z 281. Isomeric structures 12 and 13 were obtained respectively from treatment of 2m with ammonium acetate–acetic acid and the interaction between 1 and chloroacetamide in N,N-dimethylformamide (DMF) (Scheme IB).The structures of 12 and 13 were deduced from their IR spectra which revealed bands at vmax 3404 (OH), 3277, 3130 (NH), 2977, 2871 (CH3, CH2), 1657 (C�O) and 1608 cmµ1 (cyclic C�C). The UV spectrum of 12 showed bands at lmax 320, 306, 266 and 255 nm. Bands of this type are found with all aromatic azo compounds.16 A convenient method for the synthesis of the fully fused quinazolines 17 was deduced from treatment of 2-methyl/ phenyl-4-(arylmethylidene)oxazol-5(4H)-ones (14a,b) with 1 followed by cyclocondensation via hydrazinolysis in basic media.The IR spectrum of 17 showed disappearance of the NH2, NH and C�O absorption bands, indicating the formation of a cyclic structure. 154 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence. Scheme IAN N NH C6H4Cl- p O N N NH C6H4NO2- p O N N NH C6H4OMe- p O N N NH C6H4NO2- p O N N N C6H4Cl- p O N N N C6H4NO2- p O N N N C6H4OMe- p O N N N C6H4NO2- p O COCMe3 COCH2Cl CH2OH CH2 N N N N N C6H4NO2- p HCHO–piperidine–MeOH HCHO–MeOH ClCOCH2Cl ClCOCMe3 5 CH3CO2NH4 H+ 4b 3e 4a 3g 4c 3f 4d O 3e Measurements of the biocidal activity of some of the prepared compounds employing Cup-diffusion techniques17 showed that 16a is the most bactericidal and displays an effect18 equal to that of gentamycin towards E.coli. Techniques used: UV–VIS, IR, 1H NMR and mass spectroscopy; X-ray and elemental analysis References: 17 Table 1: Physical data for new compounds Schemes: 3 Charts: 4 (Fragmentation patterns of compounds 2g, 8a, 11 and 13) Received, 9th January 1996; Accepted 5th November 1996 Paper E/6/00184J References cited in this synopsis 11 P. Mishra, P. N. Gupta and A. K. Shakya, J. Indian Chem Soc., 1991, 68, 618. 14 R. M. Abdel-Rahman, Indian J. Chem., 1988, 27B, 548. 15 M. Seada, R. M. Abdel-Rahman and M. Abdel-Megid, Indian J. Heterocycl. Chem., 1993, 9. 16 O. H. Wheeler and P. H. Gore, J. Org. Chem., 1961, 26, 3298. 17 T. J. Mackie and J. E. MacCartheny, Practical Medical Microbiology, 30th edn., Churchill Livingstone, Edinburgh, London, New York, 1989. 18 S. A. Abdel-Aziz, H. A. Allimony, H. M. El-Shaaer, U. F. Ali and R. M. Abdel-Rahman, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 113, 67. J. CHEM. RESEARCH (S), 1997 155 Scheme IB S

ISSN:0308-2342    

DOI:10.1039/a600184j

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

156 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 156–157 J. Chem. Research (M), 1997, 1064–1074 A Study of the Electrochemical Synthesis of Tri-n-butylstannyldiphenylphosphine and of the Reaction between Chlorodiphenylphosphine and Alkyl Halides Hugh C. Brookes,a Elena I. Lakobaa and Michael H. Sosabowski*b aDepartment of Chemistry, University of Natal, Durban, 4014, Dalbridge, South Africa bDepartment of Pharmacy, University of Brighton, Cockcroft Building, Moulsecoomb, Brighton BN2 4GJ, UK The electrochemical synthesis of tri-n-butylstannyldiphenylphosphine is described, and a new mechanism for the electrochemical coupling between Ph2PCl and Bu3SnCl and between PH2PCl and alkyl halides is proposed.Trialkylstannylphosphines, R3SnPR2, have attracted considerable attention in the last decade owing to their usefulness in organometallic synthesis,1–4 affording compounds which would otherwise prove inaccessible. However, they are of limited use because of inherent difficulties in their preparation. This work focuses on the development of an electrochemical synthetic route using chlorodiphenylphosphine as starting material.Perichon et al.7,8 have used a mixture of Ph2PCl and an alkyl chloride or bromide in DMF (N,N-dimethylformamide) with Mg as a sacrificial anode under controlled-current conditions to prepare alkyldiphenylphosphines. The following mechanism was proposed: cathode: Ph2PCl+2eµhPh2Pµ+Clµ (3) anode: MghMg2++2eµ (4) solution: Ph2Pµ+RXhPh2PR+Xµ (5) Here we report on our attempts to repeat these findings using Bu3SnCl instead of an ordinary alkyl halide.Initially, possible interactions between the components of our system were investigated, and the formation of tetraphenyldiphosphine was detected. In the presence of an electric current, only Ph2PPPh2 was formed when Ph2PCl reacted with BunBr, Br[CH2]4Br or Bu3SnCl in an undivided electrochemical cell with Mg as a sacrificial anode under controlled potential conditions (µ1.6 vs.SCE). Other workers11 have reported that electrolysis of Ph2PCl solution in acetonitrile in the presence of an excess of PhCH2Br in a conventional two-compartment cell with Pt electrodes does not yield the expected benzyldiphenylphosphine. The following mechanism was proposed to account for the formation of the reaction products: Ph2P·PPh2+PhCH2BrhPh2P·P+Ph2(CH2Ph)Brµ (7) BrµPh2P·P+Ph2(CH2Ph)hPh2PBr+Ph2PCH2Ph (8) Ph2PCH2Ph+PhCH2BrhPh2P+(CH2Ph)2Brµ (9) We propose the following interpretation of the results as an alternative to that suggested by Perichon et al.7,8 It is known that under controlled-current conditions the potential of an electrochemical system is not always constant but can shift gradually to progressively more negative potentials. If the solution contains more than one electroactive species, eventually a new electrode reaction occurs.12 In such a system the sequence of electrochemical reactions is determined by the relative values of the reduction potentials for each compound.A sequence leading to the tertiary phosphines is proposed as follows: Ph2PCl+2eµhPh2Pµ+Clµ E1 1/2 (10) Ph2Pµ+Ph2PClhPh2P·PPh2+Cl Ph2P·PPh2+2eµn2Ph2Pµ E2 1/2 (11) Ph2P+RXhPh2PR+Xµ or Ph2P.+RXhPh2PR+X. However, if alkyl halide reduction occurs before the Ph2P·PPh2 reduction, the formation of the tetraphenyldiphosphine is primarily observed. R. or Rµ+Ph2P·PPh2hno reaction (12) Consequently, an alkyl halide with a reduction potential more negative than that of tetraphenyldiphosphine should give the alkyldiphenylphosphine as the major product under constant-current conditions.Comparison of the reduction potentials (E1/2) for Ph2PCl and Bu3SnCl in DMF at the Pt electrode showed that the first reduction wave of Bu3SnCl had a slightly less negative value than that of Ph2P·PPh2, while the second wave had approximately the same value. From these data it might be expected that the reduction of Bu3SnCl would be slightly more favourable in comparison with Ph2P·PPh2.However, the similarity of the E1/2 values suggests that at some potential both reactions occur simultaneously. This is possible because the reduction waves overlap to some extent. Both electrogenerated species will react with the constituents of the solution: Bu3SnCl+eµh[Bu3Sn.]+Clµ [Bu3Sn.]+Bu3SnClhBu3SnSnBu3+Cl. 17 [Bu3Sn.]+Ph2P·PPh2hno reaction (13) Ph2P·PPh2+2eµh2[Ph2Pµ] [Ph2Pµ]+Bu3SnClhBu3SnPPh2+Clµ (14) It is clear that the first reaction depletes the supply of Bu3SnCl necessary to provide for the second reaction.The second reaction gives tributylstannyldiphenylphosphine, the required product. This work clearly shows that: (1) Bu3SnPPh2 is synthesised in the course of the electrolysis as a result of cleavage of the P·P bond in Ph2PPPh2; (2) reduction of Bu3SnCl occurs more easily than that of Ph2PPPh2; and (3) the yield of Bu3SnPPh2 can be increased by increasing the concentration of Bu3SnCl in the mixture.Techniques used: CV, 31P NMR, MS References: 20 Table 1: Half-wave potentials for the electrochemical reduction of Ph2PCl *To receive any correspondence.J. CHEM. RESEARCH (S), 1997 157 Fig. 1(a): Cathodic reduction of Ph2PCl in DMF at Pt working electrode Fig. 1(b): CV of Ph2PCl in DMF at Pt working electrode Fig. 2: Cathodic reduction of Bu3SnCl in DMF at Pt wire electrode Fig. 3: CV of Bu3SnCl in DMF at glassy carbon rotating disc electrode Received, 26th November 1996; Accepted, 29th January 1997 Paper E/6/08005G References cited in this synopsis 1 S. E. Tunney and J. K. Stille, J. Org. Chem., 1987, 52, 748. 2 T. N. Mitchell and H.-J. Belt, J. Organomet. Chem., 1990, 386, 167. 3 D. Dakternieks and C. L. Rolls, Inorg. Chim. Acta, 1989, 161, 105. 4 H. Schumann, Angew. Chem., 1968, 81, 970. 7 J. C. Folest, J.-Y. Nedelec and J. Perichon, Tetrahedron Lett., 1987, 28, 1885. 8 J. Chaussard, J. C. Folest, J. Y. Nedelec, J. Perichon, S. Sibille and M. Troupel, Synthesis, 1990, 5, 369. 11 T. J. Hall and J. H. Hargis, J. Org. Chem., 1986, 51, 4185. 17 R. E. Dessy, T. Chivers and W. Kitching, J. Am. Chem. Soc., 1966, 88, 4543.

ISSN:0308-2342    

DOI:10.1039/a608005g

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N S N O Me NH2H H H CO2H Me 1 158 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 158–159 J. Chem. Research (M), 1997, 1101–1126 4-Acetoxy-3-[1-(2-arylamino-1-hydroxy)ethyl]azetidin- 2-ones: Intermediates for the Synthesis of Novel Carbapenems Mary J. Meegan,* Caroline M. Waldron, Raymond D. Keaveny and Anthony D. Neary Department of Pharmaceutical Chemistry, School of Pharmacy, Trinity College Dublin, 18 Shrewsbury Road, Dublin 4, Ireland 3-Vinyl- and 3-isopropenyl-azetidin-2-ones are transformed into the corresponding 4-acetoxy-3-[1-(2-arylamino- 1-hydroxy)ethyl]azetidin-2-ones and 4-acetoxy-3-[1-(2-arylamino-1-hydroxy)propyl]azetidin-2-ones, intermediates for the synthesis of novel carbapenems.Many carbapenems isolated and synthesised to date possess a 1-hydroxyethyl substituent at C-6, and the presence of this group consistently demonstrates potent antibacterial activity.1 Mastalerz et al.2 have reported improvements in activity against Gram negative bacteria, particularly against Pseudomonas aeruginosa, by replacing the hydroxy group of the hydroxyalkyl substituent at C-6 of carbapenems with an amino group.The 6-(1-aminoethyl)carbapenem 1 was demonstrated to be more active than the corresponding 6-(1-hydroxyethyl)carbapenem but was unstable in solution.3 In this work the synthesis of hitherto unreported 4-acetoxy- 3-[1-(2-arylamino-1-hydroxy)ethyl]azetidin-2-ones is described with a view to the introduction of such b-amino alcohol substituents at C-6 of carbapenems.The aminolysis of epoxides provides a convenient route to b-amino alcohols and such reactions are well documented.5,9 There are many methods available for the regioselective ring opening of epoxide with amines, e.g. using diethylaluminium amides7 and aminolead compounds.8 In this work, the cobalt(II) chloride catalysed aminolysis of 1,4-diaryl-3-(1,2- epoxyethyl)azetidin-2-ones 3a–e with aniline, p-anisidine, p-toluidine and p-chloroaniline under mild conditions was first investigated.The diastereomeric epoxides 3a–e required for this study were obtained by m-chloroperbenzoic acid (MCPBA) oxidation of trans-3-vinylazetidin-2-ones 2a–e, which were prepared by stereoselective addition of crotonyl chloride to the appropriate Schiff bases. The epoxides 3a–e were opened regioselectively on the least substituted carbon in all cases, giving rise to the corresponding b-amino alcohols 4a–i in moderate yield as diastereomeric mixtures, Scheme 1.As an alternative method for the regioselective aminolysis of b-lactam epoxides under mild conditions, the use of diethylaluminium amides7 was investigated, Scheme 2. The diethylaluminium amide nucleophiles were prepared by reaction of triethylaluminium with the appropriate aryl amines. The amides were reacted with epoxides 3a–e to generate after base catalysed hydrolysis the corresponding b-amino alcohols 4a,i, 5a–c as diastereomeric mixtures.Products 4a,i were found to be identical with those produced using the cobalt(II) catalyst reaction; however in most cases the cobalt (II) catalysed reaction afforded superior yields and ease of preparation. Additional proof of the regioselectivity of this reaction was provided by the oxidation of the b-amino alcohol product 4i to the corresponding b-aminoketone 7, Scheme 2. The aminolysis of 3-(1,2-epoxyethyl)azetidin-2-ones was now applied to 4-acetoxy-1-(4-methoxyphenyl)azetidin-2-ones affording products which could be considered as precursors for carbapenems having the b-amino alcohol type substituent at C-6.The 4-acetoxy-3-vinylazetidin-2-ones 11a,b were obtained from the 4-formyl-3-vinylazetidin-2-ones 9a,b. The 4-formyl-3-vinylazetidin-2-ones 9a,b were prepared by reaction of crotonic acid and 3,3-dimethylacrylic acid with N,Np-dip- anisylethylenediimine (8) using Mukaiyama’s reagent (2-chloro-N-methylpyridinium iodide)15 as the carboxylic acid *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 Reagents and conditions: i, MCPBA, CH2Cl2; ii, R3C6H4NH2, CoCl2, MeCNN O CH2 HO R3R4N R2 R1 N Ph Ph O CH2 O PhNH 3a–e R1 = 3,4-OCH2O, R2 = CO2Me, R3 = Ph, R4 = H R1 = R2 = R4 = H, R3 = Ph R1 = 3,4-OCH2O, R2 = CO2Me, R3 = R4 = Ph R1 = 4-OMe, R2 = H, R3 = R4 = Ph R1 = Cl, R2 = CO2Me, R3 = R4 = Ph a i a b c 4 5 7 4i i ii N N N O CHO R N O CO2H R N O OCOMe R N O OCOMe HO CH2 10a b R = H R = Me N O OCOMe R a b 9 R = H R = Me R = H R = Me 11a b R = H R = Me HN Ph 13a b R = H R = Me R 12 O a b i 8 iii iv v OMe OMe OMe OMe OMe OMe MeO ii J.CHEM. RESEARCH (S), 1997 159 activating agent followed by acid hydrolysis of the resulting 4-imino b-lactam intermediate. This method offers an alternative direct synthetic route to the 4-formyl compounds as the previously reported procedures involved reaction of the acid chloride with the diimine.16 Decarboxylation–acetoxylation of the carboxylic acids 10a,b was carried out with lead tetraacetate to afford the 4-acetoxy b-lactams 11a,b.17 Epoxidation of 11a,b with MCPBA was carried out to afford the corresponding epoxides 12a,b respectively as diastereomeric mixtures. The trans 4-acetoxy-3-(1,2-epoxyethyl)azetidin-2-ones 12a,b were treated with aniline and cobalt(II) chloride and afforded the corresponding b-amino alcohol product 13a,b Scheme 3.A procedure for the synthesis of b-lactams containing a b-amino alcohol type substituent at C-3 is described, by aminolysis of 3-(1,2-epoxyethyl)azetidin-2-ones and 3-[2-(1,2- epoxypropyl)]azetidin-2-ones, under mild conditions and without destruction of the b-lactam ring. The products 13a,b represent synthetic precursors for analogues of thienamycin and carpetimycin type carbapenem antibiotics having a b-amino alcohol function rather than a 1-hydroxyethyl or 2-hydroxypropyl C-6 substituent.Work is in progress on the elaboration of these intermediates to novel carbapenems containing a b-amino alcohol substituent at C-6. On preliminary evaluation, the 3-[1-(2-amino-1-hydroxy)- ethyl]azetidin-2-ones 4a,f and 5a displayed antibacterial activity against Escherischia coli (18), Staphylococcus aureus (Oxford), Klebsiella pneumoniae 1588 and Bacillus subtilis (Oxford) at a concentration of 1 mg mlµ1, using a radial growth assay procedure.We thank Forbairt for Postgraduate Research Scholarships (A. D. N., C. M. W.). Techniques used: 1H and 13C NMR, IR, mass spectrometry, TLC Schemes: 3 References: 20 Received, 22nd January 1997; Accepted, 6th February 1997 Paper E/7/00513J References cited in this synopsis 1 R. Southgate, Contemp. Org. Synth., 1994, 1, 417. 2 H. Mastalerz, M. Menard, E. Ruediger and J. Fung-Tomc, J.Med. Chem., 1992, 35, 953. 3 M. Menard, J. Banville, A. Martel, J. Desiderio, J. Fung-Tomc and R. A. Partyka, in Recent Advances in the Chemistry of Antiinfective Agents, ed. P. H. Bentley and R. Ponsford, The Royal Society of Chemistry, Cambridge, 1993, pp. 3–20. 5 M. Bartok and K. L. Lang, in Heterocyclic Compounds, ed. A. Hassner, Wiley, New York, 1985, vol. 42, part 3, pp. 1–196. 7 L. E. Overman and L. A. Flippin, Tetrahedron Lett., 1981, 22, 195. 8 J. Yamada, M. Yumoto and Y. Yamamoto, Tetrahedron Lett., 1989, 30, 4255. 9 J. Iqbal and A. Pandey, Tetrahedron Lett., 1990, 31, 575. 15 G. I. Georg, P. M. Mashava and X. Guan, Tetrahedron Lett., 1991, 32, 581. 16 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. 17 A. C. O’Leary, A. D. Neary, C. M. Waldron and M. J. Meegan, J. Chem. Res., 1996, (S) 368; (M) 2162. Scheme 2 Reagents and conditions: i, R3R4NAlEt2, CH2Cl2; ii, pyridinium chlorochromate Scheme 3 Reagents and conditions: i, MeCR�CHCO2H, Mukaiyama’s reagent, Et3N, CH2Cl2; ii, Jones’ reagent, Me2CO; iii, Pb(OAc)4, DMF; iv, MCPBA, CH2Cl2; v, PhNH2, CoCl2, Me

ISSN:0308-2342    

DOI:10.1039/a700513j

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

H H H H H H H 1 2 3 4 H 162 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 162–163† Dynamics of Cyclic Allenes. Conformational Energy Surface of Cyclodeca-1,2,4,5-tetraene† Issa Yavari,* Robabeh Baharfar, Davood Nori-Shargh and Ahmad Shaabani Chemistry Department, Tarbiat Modarres University, P.O. Box 14155-4838, Tehran, Iran Iterative molecular mechanics calculations using Boyd’s computer program MOLBUILD and AM1 semi-empirical SCF MO calculations for two diastereoisomeric forms of cyclodeca-1,2,4,5-tetraene are reported for four conformations and three transition states for conformational interconversions. Allenes are an important class of unsaturated hydrocarbons which contain two double bonds in an orthogonal geometry. 1,2 Ring constraints bend and twist the normally linear perpendicular allene and engender substantial strain and resultant kinetic reactivity.3 Monocyclic medium-ring diallenes with the allene groups in a ring that has more than nine members appear to be fairly stable. Simple monocyclic diallenes possess two chiral centres and should exist in two diastereoisomeric forms, one diastereoisomer being racemic and the other a meso compound.Such isomers have been isolated in the case of the 12-membered diallene cyclododeca-3,4,9,10-tetraene-1,7-dione4 and 14-membered diallene cyclotetradeca-3,4,10,11-tetraene- 1,8-dione.4 The cyclic diallenes cyclodeca-1,2,5,6-tetraene (1)5 and cyclodeca-1,2,6,7-tetraene (2)6 are available via the bis(dibromocarbene) adducts of cycloocta-1,4-diene and cycloocta-1,5-diene, respectively. However, treatment of the bis(dibromocarbene) adduct of cycloocta-1,3-diene with methyllithium at µ30 °C produces cyclodeca-1,2,4,5-tetraene as an elusive compound that affords a good yield of bicyclo[6.2.0]deca-1,7,9-triene.7 While the conformational properties of 1 and 2 have been studied both experimentally8 and theoretically,9 there are no published experimental or theoretical data on the structure or conformational features of meso- and (�)-cyclodeca- 1,2,4,5-tetraene (3 and 4).In view of the success of iterative molecular mechanics calculations and AM1 semi-empirical SCF MO calculations in investigating the conformational properties of cyclic allenes8–11 and diallenes,8,12,13 we carried out corresponding investigations of 3 and 4 and report here our results. Experimental MM calculations were carried out on an IBM 3390 computer, using Boyd’s iterative computer program MOLBUILD.14,15 The parameters used in these calculations have been previously reported.16,17 The conjugation energy terms for 3 and 4 were obtained from the torsional angle of single bonds flanked by two double bonds.A two-fold potential with a stabilization (negative strain energy) of 4.24 kcal molµ1 for the planar (0 and 180°) arrangement was chosen because this reproduces experimentally the barrier to rotation seen in buta-1,3-diene.18 Semi-empirical calculations were carried out using the AM1 method with the MOPAC 6.0 program,19 implemented on a VAX 4000-300 computer.Energy-minimum geometries were located by minimizing energy, with respect to all geometrical coordinates, and without imposing any symmetry constraints. The structures of the transition state geometries were obtained using the optimized geometries of the equilibrium conformations and the procedure of Dewar et al.20 (keyword SADDLE). We have checked that all of the conformations obtained in the present work are true local-energy minima and energy maxima, as evidenced by the fact that they all are calculated to have 3Nµ6 and 3Nµ7 real vibrational frequencies, respectively.21 Results and Discussion meso-Cyclodeca-1,2,4,5-tetraene (3).·The results of MM calculations for important geometries of 3 are shown in Table 1.The unsymmetrical twist (3-T) conformation is calculated to have the lowest strain energy. By constraining the torsional angle f89101 from 74 to 12°, a smooth conformational change occurred, leading to a transition state (3Th3TC)#.Further changing of the same torsional angle yielded another energy minimum, namely the twist-chair (3-TC) conformation, which lacks symmetry. Since 3-TC is calculated to be 0.8 kcal molµ1 above 3-T, it is expected to be significantly populated at room temperature. The calculated strain-energy barrier for interconversion of 3-T and 3-TC is 4.6 kcal molµ1.The plane-symmetrical chair (3-C) geometry is a transition state between the chiral 3-TC and its mirror-image conformation 3-TCp. The calculated strain energy for 3-C is ca. 4.9 kcal molµ1. This pathway has the lowest calculated energy of the several pathways investigated. The relevant structural parameters and heats of formation (DHf°) for various geometries of 3, as calculated by the AM1 method, are given in Table 1 and Fig. 1. The twist (3-T) conformation has the lowest calculated heat of formation.The calculated heat of formation for 3-TC is ca. 1.8 kcal molµ1 above that of 3-T. The structure of the transition-state geometries (3Th3TC)# and 3-C were obtained from MOPAC 6.0 using the optimized geometries of 3-T, 3-TC and 3-TCp conformations and the procedure of Dewar et al. (Keyword SADDLE).20 The agreement between the AM1 and MM results is fairly good (Table 1). Representative structural parameters for the important geometries of the meso-isomer (3) are given in Table 1.The internal angles are close to the unstrained values in 3-T and 3-TC, but fairly expanded in transition-state geometries. The *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 Calculated structural parameters [bond angles (y) and dihedral angles (f) in °] and energies (kcal molµ1) in various forms of meso-cyclodeca-1,2,4,5-tetraene (3) 3-T, C1 3-TC, C1 (3-Th3-TC)#, C1 3-C, CS MM AM1 MM AM1 MM AM1 MM AM1 Es a 6.08 6.92 10.68 10.96 DEs b 0.00 0.84 4.60 4.88 DHf c 75.27 77.09 79.85 82.08 DDHf b 0.00 1.82 4.58 6.81 y123 y234 y345 y456 y567 y678 y789 y8910 y9101 y1012 f10134 f2345 f3467 f5678 f6789 f78910 f89101 f91012 170 121 120 167 123 111 113 114 112 123 µ76 0 77 µ91 82 µ120 74 48 169 120 120 171 123 110 113 113 112 123 µ76 0 73 µ87 85 µ132 73 48 166 120 120 165 122 110 116 116 114 121 µ70 µ8 66 µ111 119 µ58 µ43 125 168 119 119 168 122 109 115 117 113 121 µ71 µ10 66 µ106 121 µ68 µ35 121 167 119 119 165 122 112 114 118 116 123 µ84 µ9 74 µ106 110 µ95 12 98 168 118 119 170 122 110 114 119 116 122 µ77 µ10 71 µ98 115 µ95 µ1 102 165 118 118 165 122 113 120 120 113 122 µ72 0 72 µ129 82 0 µ81 129 166 118 118 167 122 112 120 120 112 122 µ71 0 70 µ128 84 0 µ83 128 aStrain energy.bRelative to the best conformation of the same compound.cHeat of formation.J. CHEM. RESEARCH (S), 1997 163 C�C�C moieties are bent in various geometries of 3 and they are 10–15° compressed from the normal value of 180°. The C(sp3)-C(sp2)-C(sp2)-C(sp2) arrangements (f3467 and f10134) in the allenic moieties of all forms are fairly twisted from their energy minima at 90°, as a result of ring strain. Contributions to the overall strain energy in the four geometries of the meso-diallene 3, as calculated by the MM procedure, are shown in Table 2.The bond and out-of-plane bending terms are small in all forms. The transition-state geometries have higher bond-angle and torsional terms than the minimum-energy conformations. The other strain-energy contributions are substantial and vary over a relatively wide range of values. (�)-Cyclodeca-1,2,4,5-tetraene (4).·Three geometries (two energy minima and a transition state) were found to be necessary in a description of the conformational properties of the (�)-diallene (4).The most stable conformation of 4, as calculated by the MM method, is the axial symmetrical twistboat- chair (4-TBC) The calculated torsional and internal angles of 4-TBC are given in Table 3. The calculated strain energy for the second energy-minimum conformation, viz. twist-chair-chair (4-TCC) (C2) is 0.4 kcal molµ1. Conformations 4-TBC and 4-TCC are important because they are expected to be significantly populated at room temperature. The calculated strain-energy barrier (8.17 kcal molµ1) for interconversion of the two forms is substantial.This feature makes a dynamic NMR spectroscopic study of the (�)-isomer 4 attractive. The relevant structural parameters and heats of formation (DHf°) for various geometries of 4 are given in Table 3. The twist-boat-chair (4-TBC) conformation has the lowest calculated heat of formation. The calculated heat of formation of 4-TCC is 1.68 kcal molµ1 above that of 4-TBC.The structure of the transition state (4-T) was obtained from MOPAC 6.0 using the optimized geometries of 4-TBC and 4-TCC conformations and the procedure of Dewar et al.20 (see Fig. 2). Received, 10th December 1996; Accepted, 24th January 1987 Paper E/6/08314E References 1 A. Greenberg and J. F. Liebman, Strained Organic Molecules, Academic Press, New York, 1978. 2 M. Traetteberg, P. Bakken and A. Almenningen, J. Mol. Struct., 1981, 70, 287. 3 R. P. Johnson, Chem.Rev., 1989, 89, 1111. 4 P. G. Garrat, K. C. Nicolaou and F. Sondheimer, J. Am. Chem. Soc., 1973, 95, 4582. 5 M. S. Baird and C. B. Reese, Tetrahedron, 1976, 32, 2153. 6 E. V. Dehmlow and T. Stiehm, Tetrahedron Lett., 1990, 31, 1841. 7 S. Masamune, C. G. Chin, K. Hojo and R. T. Seidner, J. Am. Chem. Soc., 1967, 89, 4804. 8 F. A. L. Anet and I. Yavari, J. Am. Chem. Soc., 1977, 99, 7640. 9 I. Yavari, S. Asghari and A. Shaabani, J. Mol. Struct. (THEOCHEM), 1994, 309, 53. 10 I. Yavari, J.Mol. Struct., 1980, 65, 169. 11 I. Yavari, R. Baharfar and S. Asghari, J. Mol. Struct. (THEOCHEM), 1993, 283, 277. 12 I. Yavari, F. Aghajani and A. Shaabani, J. Chem. Res. (S), 1994, 110. 13 I. Yavari, R. Baharfar and D. Nori-Shargh, J. Mol. Struct. (THEOCHEM), 1996, in press. 14 R. H. Boyd, J. Chem. Phys., 1968, 49, 2574. 15 F. A. L. Anet and R. Anet, Tetrahedron Lett., 1985, 26, 5355. 16 F. A. L. Anet and I. Yavari, Tetrahedron, 1978, 34, 2879. 17 F. A. L. Anet and I.Yavari, J. Am. Chem. Soc., 1977, 99, 7640. 18 L. A. Carreira, J. Chem. Phys., 1975, 62, 3851. 19 J. J. P. Stewart, QCPE 581, Department of Chemistry, Indiana University, Bloomington, IN, USA; J. J. P. Stewart, J. Comput.- Aided Mol. Des., 1990, 4, 1. 20 M. J. S. Dewar, E. F. Healy and J. J. P. Stewart, J. Chem. Soc., Faraday Trans., 1984, 80, 227. 21 O. Ermer, Tetrahedron, 1975, 31, 1849; J. W. McIver, Jr., Acc. Chem. Res., 1974, 7, 72. Fig. 1 Calculated AM1 profile for conformational enantiomerization of 3-T and 3-Tp via the plane-symmetrical chair (3-C) geometry Fig. 2 Calculated AM1 profile for conformational interconversion of 4-TBC and 4-TC via the axial-symmetrical 4-T geometry Table 2 Calculated strain energies in different conformations of meso-cyclodeca-1,2,4,5-tetraene (3) and (�)-cyclodeca-1,2,4,5-tetraene (4 Strain-energy contributions (kcal molµ1) 3-T, C1 3-TC, C1 (3-Th3-TC)#, C1 3-C, Cs 4-TBC, Cs 4-TCC, C2 4-T, C2 Bond stretching Bond-angle bending Torsional strain Out-of-plane bending Non-bonded interactions Total strain energy 0.25 2.74 2.02 0.21 0.86 6.08 0.27 4.91 0.25 0.58 0.91 6.92 0.39 5.57 2.68 0.16 1.88 10.68 0.42 8.02 0.47 0.36 1.69 10.96 0.24 1.90 2.92 0.46 0.76 6.28 0.26 4.78 1.03 0.37 0.24 6.68 0.41 11.14 0.82 0.54 1.54 14.45 Table 3 Calculated structural parameters [bond angles (y) and dihedral angles ( f) in °] and energies (kcal molµ1) in various forms of (�)-cyclodeca-1,2,4,5-tetraene (4) 4-TBC, C2 4-TCC, C2 4-T, C2 MM AM1 MM AM1 MM AM1 Es a 6.28 6.68 14.45 DEs b 0.00 0.40 8.17 DHf c 75.45 77.13 87.75 DDHf b 0.00 1.68 12.30 y345 y456 y567 y678 y789 f2345 f3467 f5678 f6789 f78910 120 172 124 113 112 µ62 72 µ31 µ65 161 119 172 124 112 113 µ54 77 µ45 µ58 155 118 167 123 112 116 µ33 73 µ123 95 µ69 117 168 123 112 116 µ34 76 µ119 97 µ77 119 163 119 116 121 µ25 68 µ130 39 µ26 116 164 120 116 123 µ27 75 µ129 34 µ26 aStrain energy.bRelative to the best conformation of the same compound. cHeat of form

ISSN:0308-2342    

DOI:10.1039/a608314e

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

O R N N N N Ar O R N N N N Ar 1 2 heat N N N N O Ph F N N N N O CH3 N N N N O Ph F N N N N O CH3 N N N N O CH3 F N N N N O Ph 1b 1a 2a + 2b 2c 2d O N N N N Ar R 3 d– d+ 164 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 164–165† Intramolecularity of the Thermal Rearrangement of Allyloxytetrazoles to N-Allyltetrazolones† M. Lurdes S. Cristiano and Robert A. W. Johnstone* Department of Chemistry, University of Liverpool, Liverpool L69 3BX, UK The intramolecularity of the thermal rearrangement of 1-aryl-5-allyloxy-1H-tetrazoles 1 to 1-aryl-4-allyl-1,4-dihydrotetrazol- 5-ones 2 has been investigated through cross-over studies: the results support the hypothesis for a concerted sigmatropic rearrangement occurring through a highly polar transition state, in which a partially positively charged allyl group migrates from oxygen to nitrogen, without leaving the solvent cage. 1-Aryl-5-allyloxytetrazoles 1 (Scheme 1) rearrange thermally to give 1-aryl-4-allyltetrazolones 2 in high yield.1,2 As with the analogous Claisen rearrangement,3 this reaction has potential for producing unusual bonding patterns from readily available starting materials.Rate measurements on a series of 1-aryl-5-allyloxytetrazoles in polar and non-polar solvents have been reported.2 These studies showed that the rearrangement was unimolecular and afforded measurements of enthalpies and entropies of activation. Based on enthalpies and entropies of activation, relative rates of migration for variously substituted aryl and allyl groups in polar and non-polar solvents and a lack of electron paramagnetic resonance effects, the results suggested a rearrangement mechanism involving a cyclic polar transition state, in which a partially positively charged allyl group migrates from oxygen to nitrogen with inversion, similar to the [3,3] Claisen rearrangement of allyl aryl ethers to allylphenols4 or of allyl vinyl ethers to alkenyl carbonyl compounds.5 However, the rate studies did not show whether the rearrangement of the tetrazoles was intra- or inter-molecular, viz.whether it took place entirely within a solvent cage. By simultaneously rearranging two different allyloxytetrazoles, which are known to undergo migration at similar rates in high yield, any intermolecularity in the reaction would be expected to show up by the presence of ‘cross-over’ products. This cross-over criterion has been used successfully for other rearrangements as, for example, with the Claisen transformation of allyl aryl ethers.6 In the present experiments, a mixture of 1 - ( 4 - f l u o r o p h e n y l ) - 5 - [ ( E) - 3 - p h e n y l p r o p - 2 - e n - 1 - y l o x y ] - 1 Htetrazole 1a (R=Ph, Ar=4-fluorophenyl) and 4-[(E)-but- 2-en-1-yloxy]-1-phenyl-1H-tetrazole 1b (R=Me, Ar=Ph), for which the rates of rearrangement at 100 °C are similar,2 was examined for evidence of the formation of crossed products (Scheme 2).Results and Discussion Thermal rearrangement of a mixture of tetrazoles 1a,b (Scheme 2) would be expected to yield products 2a,b if the migration were intramolecular but products 2a,b,c,d if the reaction were wholly or partly intermolecular. Because of the mass differences of the products 2a–d, mass spectrometry is a convenient method for analysis of the products of mixed rearrangement. Molecular ions of the products of reaction at m/z 296 and 216 would imply no cross-over, but ions at m/z 296, 278, 234 and 216 would indicate that the reaction was not totally intramolecular.An equimolar mixture of compounds 1a,b in 1,1,2,2-tetrachloroethane was heated to 100 °C for 4 h, a time known to be more than sufficient for complete reaction.2 After evaporation of the solvent, the residue (X) represented an almost 100% yield of rearranged material; a 1H NMR spectrum of this residue (X) was indistinguishable from that of a material (Y) obtained by separately mixing equimolar quantities of the authentic rearrangement products 2a,b.By mass spectrometry of the crude product mixture (X) only ions at m/z 296 and 216 were observed and there were no ions at m/z 234 or 278 that exceeded the normal noise level of the mass spectrum. From the sensitivity setting of the mass spectrometer and the detectable peak heights, the maximum crossover that could have occurred was less than about 0.3% of the total reaction product. Mass spectra from the mixed rearrangement process (X) and from the authentic mixture of products (Y) were identical. Since the experiment revealed no detectable cross-over, it is reasonable to conclude that the two allyl groups were never completely free of the solvent cage for each tetrazole.The earlier hypothesis of a concerted [3,3] sigmatropic rearrangement proceeding through a charged transition state similar to that shown in structure 3,2 based on the structures of the rearranged products, on the order of reaction, on the analysis of thermal activation energies and on the negative results of EPR experiments, is further supported by these cross-over results.Scheme 1 Scheme 2 *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).J. CHEM. RESEARCH (S), 1997 165 Experimental Melting points were recorded on a Reichert microscopic apparatus and are uncorrected. Mass spectra were obtained on a VG 7070E mass spectrometer by electron ionization (EI), at 70 eV.IR spectra were recorded on a Perkin Elmer 1720X FT-IR spectrometer, liquids as films and solids as KBr disks. NMR spectra were recorded either on a Bruker WM 250 MHz FT or on a Bruker AC 200 FT spectrometer, using tetramethylsilane as internal standard. Solvents, diethyl ether and tetrahydrofuran, were freshly dried by refluxing them over sodium diphenylketyl prior to use.Other chemicals were used as purchased. Preparation of Tetrazoles 1a,b·(i) A slow stream of chlorine was bubbled through a solution of 4-fluorophenyl isothiocyanate (2 g, 14.8 mmol) in CH2Cl2 (40 mL) for 24 h. The solution was then purged of excess of chlorine by nitrogen gas, filtered and the filtrate concentrated to give N-(4-fluorophenyl)-1,1-dichloroazomethine as a colourless liquid (2.25 g, 79%); dH (CDCl3) 7.0–7.2 (m); vmax/ cmµ1 1651, 1502, 1232, 897 and 833.This product was used without further purification. Activated sodium azide (0.12 g, 1.9 mmol) was added to the N-(4-fluorophenyl)-1,1-dichloroazomethine (0.31 g, 1.61 mmol) in 1,2-dimethoxyethane (5 mL) and the mixture was stirred at room temperature for 36 h. The resulting sodium chloride was filtered off and the filtrate was evaporated to afford a colourless solid, which was recrystallized from benzene–ethanol (1:1) to give colourless crystals of the required 5-chloro-1-(4- fluorophenyl)-1H-tetrazole (0.25 g, 78%), mp 85–86 °C (lit.,7 88 °C) (Found: C, 42.5; H, 2.0; N, 28.1.Calc. for C7H4ClFN2: C, 42.3; H, 2.0; N, 28.2%); dH (CDCl3) 7.2–7.4 (m, 2 H), 7.5–7.7 (m, 2 H); m/z 198, 200 (M+, 3:1, Cl isotopes). A mixture of (E)-3-phenylprop- 2-en-1-ol (cinnamyl alcohol; 0.15 g, 1 mmol) and sodium hydride (0.048 g, 1.6 mmol) in THF (10 mL) was stirred at room temperature until effervescence had ceased, at which stage a solution of 5-chloro-1-(4-fluorophenyl)-1H-tetrazole (0.2 g, 1 mol) in THF (5 mL) was added.After the mixture had been stirred for a further 2 h, the reaction was worked up by addition of ice–water (30 mL) and extraction with diethyl ether. After drying (Na2SO4), evaporation of solvent and ‘flash’ chromatography on silica gel with CH2Cl2 as eluent, colourless crystals of 1-(4-fluorophenyl)- 5-[(E)-3-phenylprop-2-en-1-yloxy)-1H-tetrazole 1a were isolated (0.11 g, 37%), mp 83–85 °C (Found: C, 65.2; H, 4.5; N, 18.7.C16H13FN4O requires C, 64.9; H, 4.4; N, 18.9%): dH (CDCl3) 5.25 (d, 2 H, J 6 Hz), 6.4-6.6 (m, 1 H), 6.9 (d, 1 H, J 14.8 Hz), 7.2–7.6 (m, 7 H), 7.6–7.8 (m, 2 H); vmax/cmµ1 1563, 1514, 1367 and 1232; m/z 296 (M+). (ii) (E)-But-2-en-1-ol (crotyl alcohol; 1.0 g, 13.9 mmol) in dry THF (20 mL) was added to a slurry of sodium hydride (0.6 g, 14.6 mmol) in dry THF (20 ml) and the mixture was stirred at room temperature under nitrogen until effervescence had ceased (30 min).To the resulting mixture was added 5-chloro-1-phenyl-1Htetrazole (2.5 g, 13.9 mmol) in dry THF (10 mL). After the mixture had been stirred at room temperature for 2 h, the reaction products were worked up as for the tetrazole 1a above to afford a light yellow oil, which was recrystallized from light petroleum (bp 40–60 °C) to give 5-[(E)-but-2-en-1-yloxy]-1-phenyl-1H-tetrazole 1b as pale yellow crystals (1.8 g, 61%), mp 36–37 °C (lit.,8 32–33 °C) (Found: C, 61.1; H, 5.6; N, 26.0.Calc. for C11H12N4O. C, 61.1; H, 5.6; N, 25.9%); dH (CDCl3) 1.75 (d, 3 H, J 8.7 Hz), 5.05 (d, 2 H, J 7.9 Hz), 5.7–5.9 (m, 1 H), 5.9–6.1 (m, 1 H), 7.4–7.6 (m, 3 H), 7.75 (d, 2 H, J 8.3 Hz); IR, vmax/cmµ1 1597, 1560, 1505, 1448 and 761; m/z 216 (M+). N-Allyltetrazolones 2a,b.—(i) The tetrazole 1a (0.3 g, 1 mmol) was heated in 1,1,2,2-tetrachloroethane at 100 °C for 3 h. After evaporation of the solvent, 1-(4-fluorophenyl)-4-(1-phenylprop- 2-en-1-yl)-1,4-dihydrotetrazol-5-one 2a was isolated as a colourless oil (0.29 g, 98%) (Found: C, 64.8; H, 4.4; N, 18.8.C16H13FN4O requires C, 64.9; H, 4.4; N, 18.9%); dH (CDCl3) 5.26–5.52 (m, 2 H), 6.0 (d, 1 H, J 5.7 Hz), 6.39–6.55 (m, 1 H), 7.12–7.50 (m, 7 H), 7.90–8.0 (m, 2 H); vmax/cmµ1 1729, 1605, 1511, 1386, 1233 and 723; m/z 296 (M+). (ii) Similarly, 1-phenyl-4-(but-3-en-2-yl)-1,4-dihydrotetrazol-5-one 2b was prepared from the tetrazole 1b and was isolated as a colourless oil (98% yield) (Found: C, 61.0; H, 5.6; N, 26.1.C11H12N4O requires C, 61.1; H, 5.6; N, 25.9%); dH (CDCl3) 1.65 (d, 3 H, J 5.7 Hz), 4.9–5.1 (m, 1 H), 5.22–5.4 (m, 2 H), 6.0–6.2 (m, 1 H), 7.3–7.55 (m, 3 H), 7.95 (d, J 8.6 Hz); vmax/cmµ1 1729, 1599, 1504, 1382 and 757; m/z 216 (M+). Cross-over Experiment.·A mixture of 1b (0.044 g, 0.2 mmol) and 1a (0.060 g, 0.2 mmol) in 1,1,2,2-tetrachloroethane (4 ml) was heated at 100 °C for 4 h. The product was isolated by evaporation of the solvent to give an oily residue which was subjected to mass spectrometry (EI). Molecular ion peaks in the mass spectrum at m/z 296 and 216 were observed, corresponding to the molecular ions of the two tetrazolones 2a,b resulting from rearrangement of the tetrazoles, but no peaks were observed at m/z 234 or 278 that would correspond to cross-over.The appearance of the mass spectrum resulting from heating the mixture of tetrazoles 1a,b was identical with that produced by an authentic mixture of the N-allyltetrazoles 2a,b.We gratefully acknowledge the financial assistance to M. L. S. C. of JNICT (Portugal) and of the Eschenmoser Trust. Received, 11th December 1996; Accepted, 21st January 1997 Paper E/6/08333A References 1 M. L. S. Cristiano, R. A. W. Johnstone and P. J. Price, J. Chem. Soc., Perkin Trans. 1, 1996, 1453. 2 M. L. S. Cristiano and R. A. W. Johnstone, J. Chem. Soc., Perkin Trans. 1, 1996, in press; M. L. S. Cristiano, PhD Thesis, University of Liverpool, 1994. 3 P. A. Evans, A. B. Holmes and K. Russel, J. Chem. Soc., Perkin Trans. 1, 1994, 3397; K. M. Mattia and B. Ganem, J. Org. Chem., 1994, 59, 720; S. Blechert, Synthesis, 1989, 71; M. Lounasmaa, P. Hanhinan and R. Jokela, Tetrahedron, 1995, 51, 8623; P. J. Parsons, C. S. Penkett and A. J. Shell, Chem. Rev., 1996, 96, 195; P. A. Evans, A. B. Holmes, R. P. McGeary, A. Nadim, K. Russel, P. J. Ohanlon and N. D. Pearson, J. Chem. Soc., Perkin Trans 1, 1996, 123. 4 C. J. Moody, Adv. Heterocycl. Chem., 1987, 42, 203; G. B. Bennett, Synthesis, 1977, 589; F. E. Ziegler, Acc. Chem. Res., 1977, 10, 227. 5 F. E. Ziegler, Chem. Rev., 1988, 88, 1423. 6 J. F. Bunnett, in Techniques in Chemistry, Vol. VI: Investigation of Rates and Mechanisms of Reactions, part 1, ed. E. S. Lewis, Wiley, New York, 3rd edn., 1974, pp. 129–209; R. G. Pearson, J. Chem. Phys., 1955, 20, 1478. 7 J. C. Kawer and W. A. Sheppard, J. Org Chem., 1967, 32, 3580. 8 J. K. Elwood and J. W. Gates, J. Org. Chem., 1967, 32, 2956.

ISSN:0308-2342    

DOI:10.1039/a608333a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

H O N N N Ph Ar Cl Cl O O N N Cl– Ar N HO N Ar 1a–j + + solvent HO R.T. Ar = Ph Ar = 2-MeC6H4 Ar = 3-MeC6H4 Ar = 4-MeC6H4 Ar = 2-MeOC6H4 Ar = 3-MeOC6H4 Ar = 4-MeOC6H4 Ar = 2-ClC6H4 Ar = 3-ClC6H4 Ar = 4-ClC6H4 a b c d e f g h i j 1,3,4 3a–j 4a,d,g,j NaOH 166 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 166–167† Reaction of Triazene 1-Oxides: Novel Synthesis of Solid Arenediazonium Chlorides† Shaaban K. Mohamed,* Mohsen A.-M. Gomaa and Ahmed M. Nour El-Din Chemistry Department, Faculty of Science, El-Minia University, El-Minia, A.R. Egypt Treatment of 1,3-diaryltriazene 1-oxides with oxalyl chloride in dry toluene at room temperature gives only solid arenediazonium chlorides; however, treatment with acetyl and benzoyl chlorides does not afford the corresponding diazonium chlorides. In previous reports1,2 we have shown that 1,3-diaryltriazene 1-oxides form stable charge-transfer complexes (1:1) with the electron-deficient tetracyanoethylene in different solvents.1 The photolysis of these 1,3-dipoles in aromatic and nonaromatic solvents leads to their decomposition2 giving 2-hydroxyazobenzene and mono- and di-substituted biaryls.These results prompted us to study the reactivity of these oxides towards different chemical reagents. Here we report the results of our investigations of the effect of acid chlorides on 1,3-diaryltriazene 1-oxides. It has been reported3 that the analogous 1,3-dipoles, nitrones, rearranged to the isomeric amides on treatment with acetyl chloride.However the reaction of N-aryl nitrones with oxalyl chloride led to the introduction of the chlorooxalyl group at the ortho position of the N-aryl group.4 In the present work, the reaction of the 1,3-dipoles 1,3-diaryltriazene 1-oxides 1a–i with acid chlorides behaved differently. Addition of oxalyl chloride to the 1,3-dipoles 1a–i in dry toluene at room temperature gave only the arenediazonium chlorides in good yields (80–95%), Table 1. The physical and spectral properties of the diazonium salts 3a–i are summarised in Table 1.The well known instability of diazonium compounds is one of their outstanding characteristics, and they usually explode on heating above their melting points, a property which complicates both their analyses and mass spectral fragmentation. The IR spectra of 3a–i in KBr disks showed a sharp absorption characteristic of the diazonium group ·+N�N at 2250–2280 cmµ1. Because of the instability of the diazonium salt, the 1H NMR spectra could not be recorded. Chemical evidence for the diazonium salt structure was provided by coupling the salts 3a,d,g,i with an ethanolic alkaline solution (NaOH) of 2-naphthol, which afforded the corresponding azo dyes5,6 4a,d,g,i (Scheme 1).Chromatographic separation of the mother liquors did not give any pure compounds. A rationale for the formation of the arenediazonium salts 3a–i is presented in Scheme 2.It is expected from the dipolar nature of the triazene 1-oxides that the oxygen of the azoxy function will behave as a nucleophile and may attack the electron-deficient carbonyl carbon of the oxalyl chloride to form the dipoles 5a–i. Proton shift followed by decomposition of 6a–i may give rise to the diazonium salts 3a–i, chlorooxalic acid 7 and nitrene 8. In previous work7 on the thermal characterization of triazene 1-oxides, we succeeded in capturing the nitrene species 8 which underwent dimerisation to form azobenzene in low yield (0.01%; GC–MS analysis).It was too difficult to separate the dimer by preparative TLC. However, the chloroxalic acid 7 could not be separated and although there are plenty of reports8 on this acid, reference to explain the separation was not found. In contrast to the oxalyl chloride reaction, treatment of triazene 1-oxides 1a–i with acetyl chloride and benzoyl chloride did not give the corresponding arenediazonium salts but instead gave resins.Chromatographic separation gave decomposed compounds in small quantities, which could not be isolated in a pure form. Experimental All melting points were recorded on a Galenkamp melting point apparatus and are uncorrected. Oxalyl chloride, benzoyl chloride and acetyl chloride were obtained from Aldrich. Toluene was distilled and dried following the method of Vogel.9 Triazene 1-oxides 1a–i were prepared according to literature methods.10 IR spectra *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 Physical and spectral data of diazonium chlorides 3a–i Compound Yield Mp 3 (%) Colour °C vmax (KBr)/cmµ1 a bc def ghij 93 80 86 80 87 95 90 80 83 89 White Pink Buff Brown White White Grey Orange Brown White 59 (decomp.) 71–72 79–80 65 60–61 70–72 74–75 133–135 75–77 87–88 3000 (Ar–CH), 2280 (–N+�N) 3000 (Ar–CH), 2900 (aliph-CH), 2255 (–N+�N) 3030 (Ar–CH), 880 (aliph-CH), 2260 (–N+�N) 3030 (Ar–CH), 2850 (aliph-CH), 2250 (–N+�N) 3010 (Ar–CH), 2900 (aliph-CH), 2255 (–N+�N) 3030 (Ar–CH), 2885 (aliph-CH), 2265 (–N+�N) 3000 (Ar–CH), 2800 (aliph-CH), 2280 (–N+�N) 3000 (Ar–CH), 2265 (–N+�N), 775 (C–Cl) 3030 (Ar–CH), 2280 (–N+�N), 800 (C–Cl) 3030 (Ar–CH), 2260 (–N+�N), 780 (C–Cl) Scheme 1H O– N+ N N Ar Ph Cl O Cl O H O N+ N N Ar Ph C Cl O C Cl O O N N N Ar Ph C Cl O C Cl O N N Cl– Ar + – decomposition 1a–j Cl O HO O 2 5a–j –H+ – 6a–j + Ph N + 7 + 8 3a–j J.CHEM. RESEARCH (S), 1997 167 were recorded on Shimadzu 470 and Perkin Elmer 283 spectrophotometers (KBr disk). Synthesis of Solid Diazonium Chlorides 3a–i.·To a clear stirred solution of the unsymmetrical triazene 1-oxides 1a–i (1 mmol) in dry toluene (10 ml), oxalyl chloride 2 (1 mmol) in dry toluene (5 ml) was added dropwise. The reaction mixture became turbid and after 10 min at room temperature the solid diazonium chloride products precipitated.The diazonium chlorides 3a–i were separated by filtration in 80–95% yield. Reaction of Triazene 1-Oxides 1a–i with Acetyl Chloride and Benzoyl Chloride.·To a stirred solid cold (µ10 °C) solution of triazene 1-oxide (1 mmol) in dry toluene (10 ml), acid chloride (1 mmol) in dry toluene (5 ml) was added dropwise over 10 min. The reaction mixture was allowed to warm to room temperature and gradually became darker giving an oily viscous material.Separation of these resins by preparative TLC afforded multi-decomposed compounds in small quantities which could not be isolated in pure solid form. Preparation of the Azo Dyes 4a,d,g,i.·Addition of a solution of the solid diazonium salt 3a,d,g,i (1 mmol) in cold water (5 ml) to an ethanolic alkaline solution (10% NaOH) of 2-naphthol (1 mmol) at 0–5 °C gave a red precipitate. The reaction mixture was then allowed to stand at room temperature for 10 min and then filtered.The solid obtained was dried and then recrystallized from an appropriate solvent. The melting points of the product dyes were compared with those of authentic samples.5,6 4a: scarlet red (93%), mp 132 °C (lit.,5 132–133 °C). 4d: deeply red (96%), mp 133 °C (lit.,6 133–134 °C). 4g: red dye (87%), 140 °C (lit.,6 139–140 °C). 4i: bright red (94%), mp 156 °C (lit.,6 155–157 °C). Received, 17th July 1996; Accepted, 27th January 1997 Paper E/6/05013A References 1 A. M. Nour El-Din, A. A. Hassan, S. K. Mohamed, F. F. Abdel- Latif and H. A. El-faham, Bull. Chem. Soc. Jpn., 1992, 65, 553. 2 A. M. Nour El-Din, S. K. Mohamed and D. Doepp, Bull. Chem. Soc. Jpn., submitted for publication. 3 J. Hamer and A. Macaluso, Chem. Rev., 1964, 64, 473. 4 D. Liotta, A. D. Baker, N. L. Goldman and R. Engel, J. Org. Chem., 1975, 39. 5 R. P. Lastovsk and I. Zhur, J. Gen. Che.), 1948, 18, 921. 6 J. W. Raymond, Le Fevre and H. T. Liddicoet, J. Chem. Soc., 1951, 2743. 7 S. K. Mohamed, PhD Thesis, El-Minia University, 1994. 8 H. A. Abdel-Nabi, PhD Thesis, El-Minia University, 1992. 9 Text Book of Practical Organic Chemistry, ed. A. I. Vogel, Longman, London, 4th edn., 1978. 10 T. Mitsuhashi and O. Simamura, J. Chem. Soc. B, 1970, 705. Scheme 2

ISSN:0308-2342    

DOI:10.1039/a605013a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

But But ClH2C CH2Cl R HSH2C CH2 SH But But R S S + 6 3 8 But But 1 1 But R R = H R = Me R = OMe 2a 2b 2c 18 i ii 5 But But 11 9 6 2 But But Me Me 16 15 5 13 3a 3b 3c R = H R = Me R = OMe 4a 4b 4c R = H R = Me R = OMe 168 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 168–169† Synthesis and Structure of Novel 1,8-Bridged Fluorenophanes† Akihiko Tsuge,*a Yasuhiro Ueda,a Tadashi Arakia Tetsuji Moriguchi,a Kazunori Sakata,a Keizo Koya,b Shuntaro Matakab and Masashi Tashirob aDepartment of Chemistry, Kyushu Institute of Technology, Tobata-ku, Kitakyushu 804, Japan bInstitute of Advance Material Study, Kyushu University, Kasuga, Fukuoka 816, Japan A novel 1,8-bridged fluorenophane (4a) is found to assume an ‘inward-folded’ conformation with the bulky tert-butyl group located in the cavity, a situation which is different from the conformation of the corresponding dithiafluorenophane (3a).Cyclophanes are cyclic compounds consisting of aromatic units.Many aromatic components have been used in the cyclophane skeleton.1 Considerable attention has been paid to particular properties of the components, because of the strained structure of the ring system and its ability to form p-electronic interactions. It is of interest to examine the properties of a fluorene unit in cyclophane compounds, because of its aromatic nature and acidic proton. To the best of our knowledge, however, [2.2](2,7)fluorenophane is the only example2 to have been investigated so far.This is due to difficulties in introducing a functional group into sites other than the 2- and 7-positions by electrophilic reactions. In previous work3 we found that a chloromethyl group can be introduced into the 1,8-positions of the fluorene molecule by treatment with chloromethyl methyl ether in the presence of an appropriate Lewis acid. This chloromethylated fluorene should be a precursor for the synthesis of fluorenophane compounds. Thus, we describe here the synthesis of novel 1,8-bridged fluorenophanes and their conformational properties. Treatment of 3,6-di-tert-butylated fluorenophane with chloromethyl methyl ether in the presence of TiCl4 gave the 1,8-bis(chloromethyl)fluorene 1 in 58% yield.Bromination of 4-tert-butyl-m-xylene with N-bromosuccinimide (NBS), followed by treatment with thiourea afforded the bis(thiol) 2a. Compounds 2b and 2c were obtained according to reported methods.4 Cyclization of 1 and 2a–c using CsOH as a base under highly dilute conditions afforded the corresponding dithiafluorenophanes (3a–c) in 72–84% yields (Scheme 1).The 1H NMR spectra of 3a–c are summarized in Table 1. Signals for the CH2 bridge reflect the dynamic behaviour of the dithiafluorenophane. The C-9 hydrogens of 3a show a broad singlet, indicating that inversion of the ring at room temperature is slow on the NMR time-scale. In contrast, a pair of doublets with a separation of 22 Hz was observed in the spectra of 3b and 3c.These results strongly suggest that the barrier to inversion in dithiafluorenophanes depends on the bulkiness of the inner substituent (R). In order to determine for 3a the coalescence temperature and the free energy of activation for inversion, the temperature- dependent 1H NMR technique was employed. The measured barrier for the observed dynamic process is 11.54 kcal molµ1 at µ15 °C in CDCl3.‡ In contrast, there were no changes in the NMR signals for 3b or 3c, even at 150 °C in [2H6]Me2SO, indicating that 3b and 3c have rigid structures.We have already prepared various metacyclophanes consisting of three aromatic rings and confirmed their ‘inwardfolded’ conformation, which is characterized by one aromatic ring being folded into the cavity produced by the other two aromatic rings.5 Taking into account these results and the chemical shifts of the tert-butyl protons, it may be deduced that the dithia- fluorenophanes 3a–c assume a conformation in which the substituent R of the benzene ring is accommodated inside the cavity.After oxidation of 3a–c with m-chloroperbenzoic acid (MCPBA), pyrolysis was carried out in order to obtain the fluorenophanes 4a–c (Scheme 1). However, in spite of repeated trials, all attempts to prepare 4b and 4c resulted in failure, in most cases only the dimethyl compound 5 being isolated from very complex mixtures. In contrast, in the case of 3a the desired fluorenophane 4a was obtained in 29% yield.This is certainly due to steric hindrance of the substituent R during recombination of radical intermediates in pyrolysis: even when hydrogen was the substituent, the yield was not good. Data for the 1H NMR spectrum of 4a are also shown in Table 1. In 4a it is noted that the protons of the tert-butyl group attached to the benzene ring show an unexpectedly upfield shift, suggesting a conformation in which the tertbutyl group is located in the cavity formed by the p-cloud of the fluorene ring.This is in fairly good agreement with a considerable upfield shift of the aromatic protons adjacent to *To receive any correspondence (e-mail: tsuge@che.kyutech.ac.jp). †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). ‡1 cal=4.184 J. Scheme 1 Reagents and conditions: i, CsOH, EtOH;; ii, MCPBA, then 500 °C, 2 TorrBut But S H S But But H But But d 5.84 4a 3a J.CHEM. RESEARCH (S), 1997 169 the tert-butyl group. Inversion of one aromatic ring occurs during the transformation into a smaller cyclic system (Scheme 2). Further investigations of other types of 1,8-bridged fluorenophanes are in progress. Experimental All melting points are uncorrected. 1H NMR spectra were recorded at 500 MHz on a Nippon Denshi JEOL a-500 spectrometer in CDCl3 with Me4Si as an internal reference.Mass spectra were obtained on a Nippon Denshi JEOL DX-300 spectrometer at 75 eV using a direct-inlet system. Elemental analyses were carried out on a Yanaco MT-3 spectrometer. Column chromatography was performed on silica gel (Wako gel, C-300). (3-tert-Butyl-5-sulfanylmethylphenyl)methanethiol 2a.·A solution of 1,3-bis(bromomethyl)-5-tert-butylbenzene (30 g, 93 mmol) and thiourea (18.0 g, 0.24 mol) in DMSO (450 ml) was stirred at room tempearture for 15 h under an argon stream.After the reaction mixture had been poured into cold 10% aqueous NaOH (500 ml) and acidified with 10% hydrochloric acid, it was extracted with CH2Cl2. The extract was washed with water, dried over MgSO4, and evaporated in vacuo to leave a residue which was distilled to afford the bis(thiol) 2a (16.5 g, 79%) as a colourless liquid, bp 140–145 °C at 2 Torr (Found: C, 63.86; H, 8.13. C12H18S2 requires C, 63.65; H, 8.03%); m/z 226 (M+); dH 1.31 (9 H, s), 1.75 (2 H, t, J 8 Hz), 3.70 (4 H, d, J 8 Hz), 7.12 (1 H, s), 7.19 (2 H, s).Dithiafluorenophanes 3. General Procedure: Preparation of 6 , 1 5 , 1 8 - t r i - t e r t - b u t y l - 2 , 1 1 - d i t h i a [ 3 ] m e t a c y c l o [ 3 ] ( 1 , 8 ) f l u o r e n o p h a n e 3a.·A solution of 13 (1.09 g, 2.9 mmol) and 2a (0.70 g, 3.1 mmol) in EtOH–benzene (1:1; 300 ml) was added dropwise from a Hershberg funnel with stirring to a solution of CsOH (1.21 g, 8.07 mmol) and NaBH4 (0.12 g, 3.2 mmol) in EtOH (2 l) for 1 h.After solvents had been evaporated, the residue was extracted with CH2Cl2. The extract was washed with water, dried over MgSO4, and evaporated in vacuo to give 3a (1.22 g, 79%) as colourless prisms, mp 234–235 °C (from hexane) (Found: C, 79.32; H, 8.41. C35H44S2 requires C, 79.47; H, 8.40%); m/z 528 (M+); dH 1.34 (9 H, s), 1.38 (18 H, s), 2.70 (2 H, br s), 3.70 (4 H, s), 3.74 (4 H, s), 7.17 (2 H, d, J 1.5 Hz), 7.19 (2 H, s), 7.45 (1 H, s), 7.62 (2 H, d, J 1.5 Hz). 6 , 1 5 , 1 8 -T r i - t e r t - b u t y l- 2 , 1 1 -d i t h i a [ 3 ] m e t a c y c l o [ 3 ] ( 1 , 8 )f l u o r e n o - phane 3b.·3b was obtained according to the general procedure. Thus 13 (0.53 g, 1.41 mmol) and 2b4 (0.35 g, 1.46 mmol) gave 3b (0.64 g, 84%) as colourless prisms, mp 189–191 °C (from hexane) (Found: C, 79.83; H, 8.49. C36H46S2 requires C, 79.63; H, 8.56%); m/z 542 (M+); dH 1.32 (9 H, s), 1.36 (18 H, s), 1.90 (1 H, d, J 22 Hz), 2.39 (3 H, s), 2.90 (1 H, d, J 22 Hz), 3.48 (2 H, d, J 12 Hz), 3.74 (2 H, d, J 14 Hz), 3.95 (2 H, d, J 14 Hz), 3.99 (2 H, d, J 12 Hz), 7.14 (2 H, s), 7.15 (2 H, d, J 1.5 Hz), 7.61 (2 H, d, J 1.5 Hz). 6 , 1 5 , 1 8 - T r i - t e r t - b u t y l - 9 - m e t h o x y- 2 , 1 1 - d i t h i a [ 3 ] m e t a c y c l o [ 3 ] - (1,8)fluorenophane 3c.·3c was obtained according to the general procedure. Thus 13 (0.32 g, 0.85 mmol) and 2c4 (0.23 g, 0.90 mmol) gave 3c (0.34 g, 72%) as colourless prisms, mp 191–193 °C (from hexane) (Found: C, 77.58; H, 8.50.C36H46S2O requires C, 77.35; H, 8.31%); m/z 558 (M+); dH 1.32 (9 H, s), 1.35 (18 H, s), 2.03 (1 H, d, J 22 Hz), 3.21 (1 H, d, J 22 Hz), 3.51 (2 H, d, J 12 Hz), 3.60 (2 H, d, J 14 Hz), 3.86 (3 H, s), 3.93 (2 H, d, J 14 Hz), 3.99 (2 H, d, J 12 Hz), 7.13 (2 H, d, J 1.5 Hz), 7.18 (2 H, s), 7.58 (2 H, d, J 1.5 Hz). 5,13,16-Tri-tert-butyl[2]metacyclo[2](1,8)fluorenophane 4a.—The sulfone derivative of 3a (0.52 g, 0.88 mmol) was pyrolysed at 500 °C under reduced pressure (2 Torr) in a horizontal quartz tube.The resultant product was chromatographed with hexane as an eluent to afford 4a (0.12 g, 29%) from the first fraction as colourless needles, mp 296–298 °C (from hexane) (Found: C, 90.16; H, 9.66. C35H44 requires C, 90.44; H, 9.54%); m/z 464 (M+); dH 0.69 (9 H, s), 1.37 (18 H, s), 2.93–3.86 (8 H, m), 3.07 (1 H, d, J 19 Hz), 3.80 (1 H, d, J 19 Hz), 5.83 (2 H, s), 6.91 (2 H, d, J 1.5 Hz), 7.09 (1 H, s), 7.23 (2 H, d, J 1.5 Hz).Received, 5th August 1996; Accepted, 21st January 1997 Paper E/6/05440D References 1 F. V�ogtle, Supramolecular Chemistry, Wiley, Chichester, 1989; F. Diederich, Cyclophanes, The Royal Society of Chemistry, Cambridge, 1991; F. V�ogtle, Cyclophane Chemistry, Wiley, Chichester, 1989. 2 M. W. Haenel, Tetrahedron Lett., 1976, 3121; 1977, 1273. 3 A. Tsuge, T. Yamasaki, T. Moriguchi, T. Matsuda, Y. Nagano, H. Nago, S. Mataka, S. Kajigaeshi and M. Tashiro, Synthesis, 1993, 205. 4 M. Tashiro and T. Yamato, J. Org. Chem., 1981, 46, 1543. 5 A. Tsuge, T. Sawada, S. Mataka, N. Nishiyama, H. Sakashita and M. Tashiro, J. Chem. Soc., Chem. Commun., 1990, 1066; A. Tsuge, T. Sawada, S. Mataka, N. Nishiyama, H. Sakashita and M. Tashiro, J. Chem. Soc., Perkin Trans 1, 1992, 1489; A. Tsuge, H. Takeo, H. Kabashima, T. Moriguchi, S. Mataka and M. Tashiro, Chem. Lett., 1996, 425. Scheme 2 Table 1 1H NMR spectra of fluorenophanes [d values (CDCl3)] Compound But R 9-H 1 1.41 (18 H) 3.95 (s) 3a 1.33 (9 H) 7.09 2.69 (br s) 1.37 (18 H) (Ar-H) 3b 1.32 (9 H) 2.39 1.89 (d, J 22 Hz) 1.36 (18 H) (CH3) 2.90 (d, J 22 Hz) 3c 1.32 (9 H) 3.86 2.03 (d, J 22 Hz) 1.36 (18 H) (OCH3) 3.20 (d, J 22 Hz) 4a 0.69 (9 H) 7.09 3.07 (d, J 19 Hz) 1.37 (18 H) (Ar-H) 3.80 (d, J 19

ISSN:0308-2342    

DOI:10.1039/a605440d

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N N O Me N3 N3 N N O Me Cl N3 N N O Me Cl N N N N O Me N N N N N OMe N O Me 4a,b R = H, Ac N N R 1 NR 3 2a OMe MeO 2b 170 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 170–171† Photochemistry of 4,6-Diazido-3-methylisoxazolo- [4,5-c]pyridine: a Convenient Entry to 3-Methylisoxazolo[1,3]diazepine Systems† Donato Donati, Stefania Fusi and Fabio Ponticelli* Istituto di Chimica Organica, Universit`a di Siena, pian dei Mantellini, 44, 53100 Siena, Italy UV irradiation of 4,6-diazido-3-methylisoxazolo[4,5-c]pyridine in methanol gives the 3-methylisoxazolo-1,3-diazepine derivatives 3,4 by nitrogen loss and solvent addition.Following our interest on the photochemistry of heterocycles, 1 we focused our attention on diazido-isoxazolopyridines, in view of the possibility of rearrangement of the isoxazole system2 and fragmentation of the azide moiety.3 In addition, cross-over photoreactions involving both processes might be expected. The photochemistry of aromatic azides has been largely investigated as a useful access to sevenmembered aza-heterocycles.3 However, no data have been reported on the photochemical behaviour of a,ap-diazidopyridines (simple or with condensed rings), in spite of the potential synthetic interest in obtaining larger polyazaheterocyclic rings.Reaction of 4,6-dichloro-3-methylisoxazolo[4,5-c]pyridine4 with an excess of sodium azide gave the 4,6-diazido derivative 1 in good yield. When an equivalent amount of sodium azide was used, we obtained the diazide 1 and the unreacted dichloroisoxazolopyridine.Only a trace of the 4-azido- 6-chloro-3-methylisoxazolo[4,5-c]pyridine 2 was formed, as indicated by the NMR spectrum of the reaction mixture. Compound 2 can be easily prepared from the corresponding 4-hydrazino derivative4 and nitrous acid, the product existing in the solid state as the tetrazole tautomer 2b, whereas the azide form 2a is present in solution. In fact, only in the IR spectrum of a chloroform solution of this compound did we find a strong band at 2135 cmµ1, attributable to the stretching of the N3 group.Also, compound 1 exists in solution mainly in the diazide form, since the 1H and 13C NMR and UV spectra (the last both in CHCl3 and in methanol) are very similar to those of 2a. UV irradiation of 1 in methanol gave two main products, arising from 1 through the loss of one or two molecules of nitrogen followed by the addition of one or two molecules of the solvent.NMR and mass spectral analysis of both compounds did not allow any definitive conclusion about their structures. The complete configurational assignment of the isoxazolotetrazolodiazepine 3 was performed via X-ray crystallographic analysis (Fig. 1), using a crystal obtained by slow evaporation of an ethereal solution of this compound. In spite of several attempts using different solvents, we were unable to obtain well formed crystals of compound 4a.However, acetylation of 4a with acetyl chloride–triethylamine gave the diacetyl derivative 4b, which from cyclohexane –diethyl ether afforded crystals suitable for X-ray crystallographic analysis (Fig. 2). The formation of the diazepines 3 involves elimination of N2 from the azido group in position 4, ring enlargement to a cyclic carbodiimide3 and methanol addition. Similarly, in order to explain the formation of 4a, we may suppose N2 elimination from the azido group in position 6, ring enlargement and methanol addition, but in this case, the intermediate 4-azido diazepine decomposes and the resulting nitrene adds methanol without a second ring insertion.*To receive any correspondence (E-mail: donati@unisi.it). †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). ‡Atomic coordinates, thermal parameters, and bond lengths and angles have been deposited at the Cambridge Crystallographic Data Centre (CCDC).See Instructions for Authors, J. Chem. Research (S), 1997, Issue 1. Any request to the CCDC for this material should quote the full literature citation and the reference number 423/4. Scheme 1 Fig. 1 X-Ray structure of compound 3, with 30% probability thermal ellipsoids Fig. 2 X-Ray structure of compound 4b, with 30% probability thermal ellipsoidsJ. CHEM. RESEARCH (S), 1997 171 It is to be noted that, unexpectedly, the isoxazole ring is not involved in these photochemical rearrangements. These results show that this reaction is a good entry to the previously unknown isoxazolo[4,5-d]- and -[4,5-e]-[1,3]diazepine systems.Taking into account the easy opening of the isoazole moiety and the versatile addition on the intermediate carbodiimides, it is possible to prepare also several diazepine derivatives, a class of heterocycles with potential biological interest.5 Experimental IR spectra were obtained, unless otherwise stated, for KBr discs with a Perkin-Elmer 782 spectrometer. 1H and 13C NMR spectra were recorded for solutions in CDCl3 on a Bruker AC 200 instrument operating at 200 MHz for 1H and at 50 MHz for 13C. Chemical shifts are given in ppm relative to internal SiMe4. Electronimpact mass spectra (70 eV) were recorded on a VG 70 250S instrument. Photochemical reactions were carried out with a medium-pressure mercury immersion lamp (125 W) filtered and cooled with copper(II) sulfate solution (30 g dmµ3; cut off 300 nm); nitrogen was constantly bubbled through the irradiated solution.Diffractometer data were collected on a Siemens P4 diffractometer, at room temperature (293�2 °K), using graphite monochromated MoKa radiation (l=0.7107) with the w-scan technique and corrected for Lorentz and polarization effect, no absorption corrections. The structures were solved by direct methods and refined by full-matrix least-squares on F2 using the program packages SHELXTL-PC6 and SHELXL93.7‡ 4,5-Diazido-3-methylisoxazolo[4,5-c]pyridine 1.·Reaction of 4,6-dichloro-3-methylisoxazolo[4,5-c]pyridine4 with an excess of sodium azide in propan-1-ol–water, 5:1 at 60 °C for 24 h gave compound 1 as a colourless solid, yield 88%, mp 71–72 °C (from ethanol–water); vmax/cmµ1 3095 (CH), 2230, 2200, 2135 (N3), 1610, 1590 and 1450; vmax/cmµ1 (CHCl3), 2180, 2090; dH 2.56 (3 H, s, Me), 6.59 (1 H, s, 7-H); dC 11.0 (Me), 90.7 (C-7), 108.1 (C-3a), 149.0 (C-4), 153.6 (C-6), 153.8 (C-3), 171.1 (C-7a); m/z 216 (M+, 34%), 160 (6), 107 (87), 79 (34), 67 (100) (Found: C, 39.0; H, 1.9; N, 51.6.C7H4N8O requires C, 38.9; H, 1.9; N, 51.8%). 5-Chloro-9-methylisoxazolo[4,5-c][1,2,3,4]tetrazolo[1,5-a]pyridine 2b.·6-Chloro-4-hydrazino-3-methylisoxazolo[4,5-c]pyridine4 (10 mmol) dissolved in 3 M hydrochloric acid (30 cm3) was treated with sodium nitrite (10 mmol) and the mixture was repeatedly extracted with diethyl ether.Solvent evaporation and sublimation in vacuo gave compound 2b as a colourless solid, yield 62%, mp 95–96 °C; vmax/cmµ1 3060 (CH), 1650 (C�N), 1580, 1515; vmax/cmµ1 (CHCl3) 2230, 2135; dH 2.59 (3 H, s, Me), 7.20 (1 H, s, 6-H); dC 11.2 (Me), 102.2 (C-6), 109.8 (C-9a), 149.7 (C-10), 149.8 (C-5), 153.9 (C-9), 170.4 (C-6a); m/z 209/211 (M+, 42/14%), 181/183 (12/4), 146 (29), 114 (22), 88 (43), 67 (100) (Found: C, 39.9; H, 1.9; N, 33.6.C7H4ClN5O requires C, 40.1; H, 1.9; N, 33.4%). Irradiation of Compound 1.·Compound 1 (2 mmol) in methanol (100 ml) was irradiated until about half of the starting material had disappeared (TLC). Solvent evaporation and column chromatography on silica gel [chloroform–methanol 95:5 (v/v)] gave, after the unreacted compound 1 (0.8 mmol), 5-methoxy-7-methyl- 10H-isoxazolo[5,4-f][1,2,3,4]tetrazolo[1,5-c][1,3]diazepine 3 as a white solid, yield 15%, mp 155–156 °C (from diethyl ether); vmax/ cmµ1 1700 (C�N), 1625, 1590, 1440; dH 2.34 (3 H, s, Me), 4.20 (3 H, s, OMe), 4.65 (2 H, s, CH2); dC 8.9 (Me), 22.7 (C-10), 56.9 (OMe), 121.2 (C-6a), 141.3 (C-5), 150.5 (C-10a), 150.9 (C-9a), 158.4 (C-7); m/z 220 (M+, 10%), 191 (3), 151 (14), 136 (9), 123 (46), 108 (100), 83 (18), 66 (69) (Found: C, 43.8; H, 3.7; N.C8H8N6O2 requires C, 43.6; H, 3.7; N, 38.2%). Crystal Data for 3: C8H8N6O2, Mr=220.20, orthorhombic, space group Fdd2, a=17.244(3), b=34.136(7), c=6.802(1) Å, V=4003.9(12) Å3, Z=16, Dc=1.461 Mg mµ3, F(000)=1824, m=0.112 mmµ1, crystal dimensions 0.15Å0.20Å0.65 mm. 1565 unique reflections were collected. Non-hydrogen atoms were refined as anisotropic, hydrogen atoms were located in the difference- Fourier map and refined as isotropic. Final R1=0.042, wR2=0.091 for 176 parameters. Largest difference peak in the Fourier map was 0.207 e.ŵ3, maximum shift/esd=0.425 for U11 of H16A. Further elution afforded 6,8-dimethoxy-3-methyl-5,6-dihydro- 4H-isoxazolo[4,5-e][1,3]diazepin-4-imine 4a as a yellowish solid, yield 25%, mpa330 °C (from benzene–hexane); vmax/cmµ1 3400 (NH), 3150br (NH), 1680 (C�N), 1635, 1610, 1550, 1520; dH 2.48 (3 H, s, Me), 3.57, 3.69 (each 3 H, 2 s, 2ÅOMe), 5.63 (1 H, s, CH); dC 11.2 (Me), 54.8 (6-OMe), 55.5 (8-OMe), 82.5 (C-8), 106.2 (C-3a), 155.0 (C-4), 155.7 (C-6), 158.9 (C-3), 172.4 (C-8a); m/z 224 (M+, 47%), 223 (16), 209 (59), 194 (70), 193 (100), 181 (79), 168 (28), 136 (40), 122 (18), 107 (26), 81 (32) (Found: C, 47.9; H, 5.2; N, 25.2.C9H12N4O3 requires C, 48.2; H, 5.4; N, 25.0%). N - (7 - Acetyl- 6,8 - dimethoxy- 3 - methyl- 7,8 - dihydro- 4H - isoxazolo[4,5 - e] [1,3]diazepin-4-ylidene)acetamide 4b.·To a solution of compound 4a (1 mmol) in anydrous dichloromethane (16 cm3) and triethylamine (0.3 cm3) acetyl chloride (0.28 cm3) was added. After 30 min, water was added and the organic layer was washed with water and evaporated to give, after column chromatography on silica gel with diethyl ether–hexane 3:1 (v/v), compound 4b as colourless crystals, yield 78%, mp 141–142 °C (from cyclohexane–diethyl ether); vmax/ cmµ1 1717 (CO), 1709 (CO), 1660, 1640, 1605, 1435; dH 2.21, 2.32 (each 3 H, s, 2ÅMeCO), 2.48 (3 H, s, Me), 3.54, 3.93 (each 3 H, 2 s, 2ÅOMe), 6.74 (1 H, s, CH); dC 11.6 (Me), 22.9, 25.0 (2ÅMeCO), 76.8 (C-8), 112.6 (C-3a), 144.0 (C-4), 149.5 (C-6), 159.5 (C-3), 167.5 (C-8a), 169.2, 185.8 (2 CO); m/z 308 (M+, 10%), 293 (38), 251 (100), 225 (36), 219 (34), 191 (18), 43 (79) (Found: C, 50.4; H, 5.1; N, 18.2.C13H16N4O5 requires C, 50.6; H, 5.2; N, 18.2%). Crystal data for 4b. C13H16N4O5, Mr=308.30, monoclinic, space group C2/c, a=16.580(1), b=11.750(1), c=16.664(1) Å, b=101.05(1)°, V=3109.1(4) Å3, Z=8, Dc=1.317 Mg mµ3, F(000)=1296, m=0.103 mmµ1, crystal dimensions 0.20Å0.45Å 0.60 mm. 5314 reflection were collected with 4464 unique reflections (Rint=0.0160). Non-hydrogen atoms were refined as anisotropic. Hydrogen atoms were located in the difference Fourier map and refined as isotropic with a common displacement parameter free to refine for the methyl groups.Final R1=0.051, wR2=0.138 for 249 parameters. Largest difference peak in the Fourier map was 0.232 e ŵ3, maximum shift/esd=0.103 for y/b of H17C. The availability of the mass spectrometer and of the X-ray diffractometer in the ‘Centro di Analisi e Determinazioni Strutturali’ of the University of Siena is gratefully acknowledged.This work was supported by the ‘Ministero dell’Universit` a e della Ricerca Scientifica e Tecnologica’ (MURST). Received, 16th December 1996; Accepted, 3rd February 1997 Paper E/6/08413C References 1 D. Donati, S. Fusi and F. Ponticelli, Tetrahedron Lett., 1996, 37, 5783 and references cited therein. 2 D. Donati, F. Ponticelli, P. Bicchi and M. Meucci, J. Phys. Chem., 1990, 94, 5271. 3 A. Reisinger and C. Wentrup, Chem. Commun., 1996, 813 and references cited therein; J. C. Hayes and R. S. Sheridan, J. Am. Chem. Soc., 1990, 112, 3879; C. J. Shields, D. R. Chrisope, G. B. Schuster, A. J. Dixon, M. Poliakoff and J. J. Turner, J. Am. Chem. Soc., 1987, 109, 4723; C. Wentrup and H. W. Winter, J. Am. Chem. Soc., 1980, 102, 6161; Y. Z. Li, J. P. Kirby, M. W. George, M. Poliakoff and G. B. Schuster, J. Am. Chem. Soc., 1988, 110, 8092. 4 G. Adembri, A. Camparini, F. Ponticelli and P. Tedeschi, J. Chem. Soc., Perkin Trans. 1, 1975, 2190. 5 R. I. Fryer and A. Walser, in Bicyclic Diazepines, ed. R. I. Fryer, John Wiley, New York, 1991, pp. 130–131. 6 G. M. Sheldrick, SHELXTL-PC, Siemens Analytical X-Ray Instruments, Madison, Wisconsin, USA, 1990. 7 G. M. Sheldrick, SHELXL93, Program for Crystal Structure Solution, University of Gottingen, Germany, 199

ISSN:0308-2342    

DOI:10.1039/a608413c

出版商:RSC    

年代:1997

数据来源: RSC