摘要:

S S 1 J. CHEM. RESEARCH (S), 1997 267 J. Chem. Research (S), 1997, 267 J. Chem. Research (M), 1997, 1882–1888 Synthesis and X-Ray Crystal and Molecular Structure of 1,6-Bis(3-thienyl)hexane Penny A. Chaloner,* Sumudu R. Gunatunga and Peter B. Hitchcock School of Chemistry, Physics and Environmental Science, University of Sussex, Falmer, Brighton BN1 9QJ, UK 1,6-Bis(3-thienyl)hexane has been prepared and characterised in an X-ray diffraction study. There is considerable interest in polythiophenes and oligothiophenes because they are conducting when doped and may be used for third harmonic generation.1 We report here that 1,6-bis(3-thienyl)hexane (1) is prepared by the coupling of 1,6-bis(bromomagnesiohexane) with 3-bromothiophene in the presence of [NiCl2(dppp)],14† the product being isolated by distillation followed by low temperature recrystallisation. It did not prove possible to cyclise 1 under oxidative conditions using palladium(II).16 Bromination of 1 (NBS–DMF†,17) gave 1,6-bis(2-bromo-3-thienyl)hexane in reasonable yield, but successful cyclisation of the bromo compound also proved elusive.The structure of 1 was determined (direct methods, SHELXS-86, SHELXL-93, R1=0.070, wR2=0.175) by X-ray crystallography (Fig. 1); the molecule lies across a crystallographic inversion centre. The thiophene ring is planar and unstrained, and the molecular dimensions are similar to those in bithiophene.2 Techniques used: 1H and 13C NMR spectroscopy, X-ray diffraction References: 23 Fig. 2: Packing diagram for 1 Tables 1, 2: Atomic coordinates, bond lengths and angles for 1 Received, 21st November 1996; Accepted, 6th May 1997 Paper E/6/07896F References cited in this synopsis 1 J. Roncali, Chem. Rev., 1992, 92, 711. 2 P. A. Chaloner, S. R. Gunatunga and P. B. Hitchcock, Acta Crystallogr., Sect. C, 1994, 50, 1941. 14 K. Tamao, K. Sumitani and M. Kumada, J. Am. Chem. Soc., 1972, 94, 4374. 16 I. V. Kozhevnikov and K. I. Matveev, Russ. Chem. Rev., 1978, 47, 649. 17 P. Bauerle, F. Wurthner, G. Gotz and T. Effenberger, Synthesis, 1993, 1099. *To receive any correspondence. †Abbreviations used: dppp=1,3-(diphenylphosphino)propane; NBS=N-bromosuccinimide. Fig. 1 Structure of 1,6-bis(3-thienyl)hexane) (1). C14H18S2, M=250.4, monoclinic, a=5.960(2), b=17.952(7), c=6.629(2) Å, b=107.36(3)°, V=677.0(4) Å3, space group P21/n (nonstandard No. 14), Z=2, Dx=1.23 g cmµ3. R1=0.070, wR2=0.175. Selected bond lengths (Å) and angles (°): S–C(1) 1.704(4); S–C(4) 1.700(4); C(1)–C(2) 1.360(5); C(2)–C(3) 1.411(5); C(3)–C(4) 1.390(5) Å. C(1)–S–C(4) 92.7(2); S–C(1)–C(2) 113.1(3); C(1)–C(2)–C(3) 110.0(4); C(2)–C(3)–C(4) 114.9(4); S–C(4)–C(3) 109.2(3)

ISSN:0308-2342    

DOI:10.1039/a607896f

出版商:RSC    

年代:1997

数据来源: RSC

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PhNHCOC Cl N NHC6H4X PhNHCOC NNC6H4X + – N N N N PhNHCO C6H4X C6H4X CONHPh + PhNHCOCONHNHC6H4X H2O –HCl 2 3 4 a X = 4-MeO b X = 4-Me c X = H d X = 4-Cl e X = 3-Cl f X = 4-EtOCO g X = 3-NO2 h X = MeCO i X = 4-NO2 1 PhNHCOC Cl NNHC6H4X + Et3N PhNHCOC Cl NNHC6H4X + Et3NH + Ka (fast) PhNHCOC Cl NNC6H4X PhNHCOC NNC6H4X + Cl– + – k1 (slow) PhNHCOC NNC6H4X + Cl– + – – – 268 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 268–269 J. Chem. Research (M), 1997, 1870–1881 Kinetics and Mechanism of Dehydrochlorination of N-Aryl 2-Oxo-2-phenylaminoethanehydrazonoyl Chlorides and their Mass Spectra Ahmad S.Shawali,* Nehal M. Elwan and Ahmad M. Awad† Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt The dehydrochlorination mechanism of the title compounds in solution and inside a mass spectrometer is studied. A number of studies on the chemistry of N-aryl 2-oxo-2- phenylaminoethanehydrazonoyl chlorides 1 have been reported in the literature,1,2 However, the kinetics of the base catalysed dehydrochlorination of such compounds have not yet been reported. We now report the kinetics and mechanism of such a process.In addition, the mass spectra of 1 were also studied to compare their unimolecular reactions in the mass spectrometer to those that would occur under normal solution conditions. A series of compounds 1a–i were prepared by reported methods.3 The structures of the new derivatives 1a and 1h were substantiated by both elemental and spectral (IR, 1H NMR and mass) analyses.Treatment of 1 with triethylamine in 1,4-dioxane–water (4:1 v/v) at 25 °C gave a mixture of the corresponding oxanilic hydrazide 3 and 1,4-diaryl-1,2,4,5- tetrazine 4. Such products are undoubtedly formed via the addition of water to the nitrilium imide 2 and by a headto- tail dimerization of 2 which is generated in situ by the action of triethylamine on 1 (Scheme 1). The kinetics of the formation of 2 from 1 were carried out under pseudo-first order conditions by keeping an excess (Å10 or greater) of triethylamine over 1 in 1,4-dioxane–water (4:1 v/v) at 25�0.1 °C with an ionic strength of 0.1.The reactions were followed potentiometrically up to 90% reaction extent by monitoring the increase in the chloride ion concentration using an ion selective electrode. The ionic strength was maintained at 0.1 in all the kinetic runs by the addition of the appropriate volume of sodium nitrate solution (5 M) in the same solvent system.The pseudo-first-order rate constant, k0, was computed from the linear (r2a0.990) least squares plot of log (Cl µCt) vs. time where Cl and Ct are the concentrations of the chloride liberated at infinite time and time t, respectively. The second-order rate constant, k2, was determined from the relation k2=k0/[Et3N]. In all cases, the plots of k0 vs. [Et3N] have zero intercepts indicating that the uncatalysed reaction is negligible under the reaction conditions employed.The second-order rate constant, k2, gave an excellent correlation with the substituent constant sµx . The equation of the regression line is: log k2=0.37sµx µ0.77; where r=0.940 and s=�0.09. A mechanism compatible with the small r2 value (0.37) is presented in Scheme 2. According to this suggested mechanism, it can be shown that k2=Kak1 and in turn the overall reaction constant r2 will be the algebraic sum of ra and r1. These two reaction constants are expected to have opposite algebraic signs, ra being positive whereas r1 being negative.Such opposite effects would thus lead to a small r2. This conclusion was substantiated by measuring the acid dissociation constants, pKa, of the related hydrazone series 5a–i in 1,4-dioxane–water (4:1 v/v) at 25�0.1 °C and ionic strength of 0.1. The choice of 5 was based on the similarity of the inductive effects of the CN and Cl groups (sI values of CN and Cl are 0.60 and 0.47, respectively).5 PhNHCOC(CN)�NNHC6H4X PhC(Br)�NNHC6H4X 5 6 PhC(Cl)�NC6H4X 7 The pKa data of 5a–i also showed an excellent correlation with sx.The equation of the regression line is: log Ka=1.18sx µµ0.87 where r=0.996 and s=�0.01. Substitution of the values of ra (1.18) and r2 (0.37) in the equation r2=ra+r1 gives a r1 value of µ0.81 which compares favourably with that (µ0.63) reported for the heterolysis of the C·Br bond of N-aryl benzenecarbohydrazonoyl bromides 6 in the same solvent system and at the same temperature.7 Furthermore, a comparison of the value of r1 (µ0.81) obtained in this work with that reported for the heterolysis of the C·Cl bond in the imidoyl chlorides 7 (r7=µ2.75) indicates that the transmission factor pp=(r1/r7) of the substituent effects for the trivalent anionic nitrogen bridge is 0.29.This small efficiency of anionic nitrogen to transmit substituent effects indicates that the changes in Ka are dominant in the studied reaction, that is the changes in k2 (=Kak1) are mainly due to changes in Ka.*To receive any correspondence. †Abstracted from the MSc thesis of A. M. Awad, University of Cairo, 1995. Scheme 1 Scheme 2PhNHCOC Cl N PhNHCOC NNHAr –H• –HCl NHAr + + PhNHCOC NNHAr + –Cl [M]+ [M–HCl]+ –PhNCO HC NNAr + –PhNCO ArN + [M–Cl]+ –PhNCO HC NNHAr + –HCN ArNH + . J. CHEM. RESEARCH (S), 1997 269 The mass spectra show that the molecular ions of 1 seem to undergo fragmentation via the two possible routes outlined in Scheme 3.The data indicate that the ions [MµCl]+ are considerably less abundant than [MµHCl]+ indicating that the formation of the latter is more favourable than the formation of the former azocarbocation. Furthermore, the data reveal that the abundance of the [MµHCl]+, which formally corresponds to the nitrilium imide seems to depend on the nature of the substituent of the N-aryl of the hydrazone moiety which is increased by electron-withdrawing substituents.Techniques used: Potentiometry, spectrophotometry, correlation analysis, mass spectrometry References: 12 Fig. 1: Plots of k2 for the base catalysed dehydrochlorination of 1a–i and pkas for the acid ionization of 5a–i against the substituent constant sx Table 1: Melting points and spectral data of the new compounds 1a,h,4c and 5f,h Table 2: Second-order rate constantss, k2, for dehydrochlorination of 1a–i and acid dissociation constants, pKa, of 5a–i in 1,4-dioxane– water (4:1 v/v) at 25 °C and ionic strength of 0.1 Table 3: The principal peaks in the mass spectra of the hydrazonoyl chlorides 1a–i Received, 2nd December 1996; Accepted, 18th April 1997 Paper E/6/08117G References cited in this synopsis 1 A. S. Shawali, Chem. Rev., 1993, 93, 2731. 2 A. S. Shawali and C. Parkanyi, J. Heterocycl. Chem., 1980, 17, 883. 3 A. S. Shawali and A. Osman, Tetrahedron, 1971, 27, 2517. 5 S. Y. Hong and J. E. Baldwin, Tetrahedron, 1965, 24, 3787. 7 F. L. Scott, M. Cashman and A. F. Hegarty, J. Chem. Soc., B, 1971, 1607. 8 A. F. Hegarty, J. D. Cronin and F. L. Scott, J. Chem. Soc., Perkin Trans. 2, 1975,

ISSN:0308-2342    

DOI:10.1039/a608117g

出版商:RSC    

年代:1997

数据来源: RSC

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N N R O– O– R + + 1 N N C –O O– C + + a X = COMe c X = CO2Me X Me Me X Me Me 3 270 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 270–271 J. Chem. Research (M), 1997, 1801–1809 Crystal Structure of (E)-1,2-Bis(1,1-dimethyl- 2-oxopropyl)diaz-1-ene-1,2-diium-1,2-diolate, the trans-Dimer of 3-Methyl-3-nitrosobutan-2-one Brian G. Gowenlock and Kevin J. McCullough* Department of Chemistry, Heriot-Watt University, Riccarton, Edinburgh EH14 4AS, UK The solid state structure of (E)-1,2-bis(1,1-dimethyl-2-oxopropyl)diaz-1-ene-1,2-diium-1,2-diolate, (3a), the trans-dimer of 3-methyl-3-nitrosobutan-2-one, has been determined by X-ray crystallographic analysis; subsequent comparison of the observed geometrical parameters for 3a with the literature values for eleven other trans or (E)-dimers suggests that there is no correlation between the N·N distances in these dimers and their respective rates of dissociation to monomer in solution.The results of our previous X-ray crystallographic studies1–3 of trans-azodioxy compounds (1) [trans- or (E)-dimeric nitroso compounds] along with other published structural data for related compounds indicate that the molecular geometry of the central coplanar C2N2O2 unit varies only slightly with alteration of the organic group R despite the marked differences exhibited by these compounds in their respective dissociation equilibria in solution at room temperature.We now report the single crystal X-ray analysis of (E)-1,2-bis(1,1- dimethyl-2-oxopropyl)diaz-1-ene-1,2-diium-1,2-diolate (3a), the trans-dimer of 3-methyl-3-nitrosobutan-2-one, prepared by the nitrosation of 3-methylbutan-2-one9 and recrystallised from chloroform–light petroleum (bp 60–80 °C).6 The molecular structure is illustrated in Fig. 1, and the observed bond distances and angles for 3a around the C2N2O2 moiety are compiled along with those obtained previously for other trans dimers in Table 3. Molecule 3a clearly has the trans- or (E)-configuration and, in a similar fashion to the related compound 3c, it adopts a low symmetry Ci conformation, presumably to minimise intramolecular steric interactions between the acetyl group and the distal NO group.3 Analysis of the structural data in Table 3 does not reveal any strong correlations between the N·N bond length, or indeed any other geometrical parameter, in dimeric nitroso compounds and the ease of dissociation to the monomer in solution.This is particularly true for compounds 3a and 3c which are structurally similar but markedly different in terms of their respective rates of dissociation.6 We conclude, therefore, that the dissociation process, although necessarily accompanied by stretching of the N·N bond, also involves other marked structural changes in the transition state as has been stated elsewhere.21,22 Crystal Data.·C10H18N2O4, Mr=230.3, colourless prisms, monoclinic, space group P21/n (non-standard setting of No. 1 4), a=6.7448(3), b=9.1438(7), c=10.3286(6) Å, b=104.829(12)°, V=615.78(7) Å3, Z=2 (the dimeric molecule sits on a crystallographic centre of symmetry), Dc= 1.242 g cmµ3, F(000)=248, m(Mo-Ka)=0.096 cmµ1. The intensity data were collected on an Enraf–Nonius FAST area detector diffractometer [temperature 293(2) K; y range 3.95–29.87°; µ9RhR6, µ11RkR12, µ14RlR12] *To receive any correspondence (e-mail: k.j.mccullough@ hw.ac.uk). Fig. 1 The molecular structure of the dimeric nitroso compunds 3a in the solid state (ORTEP;12 the non-hydrogen atoms are represented by 50% probability ellipsoids and the hydrogen atoms by spheres of arbitrary radius) Table 3 Bond-length and bond-angle data for trans-dimeric nitroso compounds (RNO)2 Bond length (Å) Bond angles (°) R NN NO CN CNN CNO NNO Ref. 2,6-Pri 2-C6H3 NO2CH2CH2 cyclo-C6H11 2-HO2C·C6H4 2-NO2·C6H10 PhCHNO2CH2 Norbornan-1-yl 4-I-C6H4 But Me2C·NO2 Me2C·CO2Me Me2C·COMe 1.323(2) 1.304(6) 1.319(6) 1.308(3) 1.302(4) 1.301(4) 1.308(5) 1.316(7) 1.309(2) 1.329(3) 1.322(3) 1.318(2) 1.267(2) 1.262(3) 1.272(6) 1.267(3) 1.274(3) 1.269(3) 1.269(5) 1.279(5) 1.265(2) 1.251(2) 1.269(3) 1.267(2) 1.467(2) 1.470(4) 1.488(6) 1.460(3) 1.487(2) 1.479(3) 1.483(5) 1.467(6) 1.533(2) 1.506(2) 1.504(3) 1.510(2) 118.16(12) 117.4(4) 118.4(4) 117.1(2) 117.4(3) 118.6(3) 119.2(3) 118.0(5) 119.91(14) 116.7(2) 117.4(2) 117.1(2) 120.86(13) 121.3(3) 121.4(4) 120.5(2) 121.4(2) 120.9(2) 120.7(3) 120.3(4) 119.65(14) 121.2(1) 122.4(2) 122.19(11) 120.93(13) 121.1(3) 120.2(4) 122.3(2) 121.2(2) 120.5(3) 120.1(3) 121.6(5) 120.41(15) 121.9(2) 120.2(2) 120.3(2) 2 13 14 15 16 16 17 18 1 19 3 This workJ.CHEM. RESEARCH (S), 1997 271 using graphite-monochromated Mo-Ka X-radiation (l 0.71073 A) and w-scanning.10 The structure was solved by direct methods (SHELXS-8611) and refined by full-matrix least-squares methods on F2 (SHELXTL/PC12) using all F0 2 data and anisotropic temperature factors for all the nonhydrogen atoms.At convergence, the discrepancy factors R and wR2 were 0.048 and 0.082 respectively for 851 observed intensities [F0a4s(F0)]. The weighting scheme, w=1/[s2(F0 2 )] was found to give satisfactory analysis of variance. We thank Professor M. B. Hursthouse (University of Wales, Cardiff) for access to data collection facilities via the EPSRC X-ray Crystallographic Data Collection Service. Technique used: X-ray crystallography References: 21 Table 1: Atomic coordinates for 3a Table 2: Derived bond lengths and angles and torsion angles for 3a Table 4: Anisotropic displacement parameters for 3a Table 5: Hydrogen coordinates and isotropic displacement parameters for 3a Fig. 2: A least-squares fit of the structures of the dimeric nitroso compounds 3a and 3c Received, 16th January 1997; Accepted, 24th April 1997 Paper E/7/00397H References cited in this synopsis 1 B. G. Gowenlock, K. J. McCullough and R. B. Manson, J. Chem.Soc., Perkin Trans. 2, 1988, 701. 2 B. G. Gowenlock and K. J. McCullough, J. Chem. Soc., Perkin Trans. 2, 1989, 551. 3 B. G. Gowenlock and K. J. McCullough, J. Chem. Res., 1993, (S), 360; (M) 2481. 6 L. Batt and B. G. Gowenlock, J. Chem. Soc., 1960, 376. 9 J. G. Aston, D. F. Menard and M. G. Mayberry, J. Am. Chem. Soc., 1932, 54, 1530. 10 M. B. Hursthouse, A. I. Karaulov, M. Ciechanowicz-Rutkowska, A. Kolasa and W. Zankowska-Jasinska, Acta Crystallogr., Sect. C, 1992, 48, 1257. 11 SHELXS-86, G. M. Sheldrick, Acta Crystallogr., Sect A, 1990, 46, 467. 12 SHELXTL/PC (ver. 5.03), G. M. Sheldrick, Siemens Analytical X-ray Instruments, Madison, WI, USA. 13 F. P. Boer and J. W. Turley, J. Am. Chem. Soc., 1969, 91, 1371. 14 M. Tanimura, K. Kobori, M. Kashiwagi and Y. Kinoshita, Bull. Chem. Soc. Jpn., 1970, 43, 1962. 15 D. A. Dieterich, I. C. Paul and K. Y. Curtis, J. Am. Chem. Soc., 1974, 91, 1371. 16 K. W. Chiu, P. D. Savage, G. Wilkinson and D. J. Williams, Polyhedron, 1985, 4, 1941. 17 M. L. Greer, H. Sarker, M. E. Medicino and S. C. Blackstock, J. Am. Chem. Soc., 1995, 117, 10 460. 18 D. A. Fletcher, B. G. Gowenlock, K. G. Orrell, V. ¢�Sik, D. E. Hibbs, M. B. Hursthouse and K. M. A. Malik, J. Chem. Soc., Perkin Trans. 2, 1996, 191. 19 B. Tinant, J. P. Declerq and O. Exner, Bull. Soc. Chim. Belg., 1987, 96, 149. 21 R. Hoffman, R. Gleiter and F. B. Mallory, J. Am. Chem. Soc., 1970, 92, 1460. 22 T. Minato, S. Yanabe and I. Oda, Can. J. Chem., 1982, 60, 274

ISSN:0308-2342    

DOI:10.1039/a700397h

出版商:RSC    

年代:1997

数据来源: RSC

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S S O O O O O O 1 2 R* R 3 4 4a O OH O H O S S R* R R* R 8 H SCl R* R 5 –HCl 1/2 S S R* R R R* 7 S R* R R R* 6 R* R H H –HCl H H –HCl + SCl S S HO O O OH 9 S S O HO O OH 10 Cl Cl 272 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 272–273 J. Chem. Research (M), 1997, 1810–1827 Organometalloidal Compounds with o-Phenylene Substituents. Part 29.1 Reaction of Sulfur Dichloride with 2-Methoxyphenol: Isolation and Characterization of 2,8-Dihydroxy-3,7-dimethoxy- and 1,6-Dichloro- 2,7-dihydroxy-3,8-dimethoxy-thianthrene Volker Mansel, Stefan Marthe, Martin Oberjat and G�unter Klar* Institut f�ur Anorganische und Angewandte Chemie der Universit�at Hamburg, Martin-Luther- King-Platz 6, D-20146 Hamburg, Germany From 2-methoxyphenol (4) and sulfur dichloride a wealth of compounds are formed, but the reaction conditions can be varied in such a way that either 2,8-dihydroxy-3,7-dimethoxythianthrene (9) or 1,6-dichloro-2,7-dihydroxy- 3,8-dimethoxythianthrene (10) is formed predominantly; both compounds are characterized by X-ray crystallographic analysis.Aromatic systems possessing two activating substituents in the ortho-positions react with sulfur dichloride to form thianthrenes. Thus, from 1,2-dimethoxybenzene (1), 2,3,7,8-tetramethoxythianthrene (2) is obtained.2 From systems like 3 with two different substituents, two isomers, one, 7, with a cisoid, the other, 8, with a transoid arrangement of the substituents, are to be expected.According to Scheme 1 the predominant formation of 7 is favoured by a quick addition of sulfur dichloride to 3, provided the activation by R in comparison with R* is stronger. In contrast, isomer 8 is favoured by a slow addition of sulfur dichloride. In this paper the reaction of sulfur dichloride with 2-methoxyphenol (4) is studied. Although the hydroxy and methoxy substituents show similar electronic effects in electrophilic substitution reactions,4,5 the behaviour of 4 according to Scheme 1 seemed possible, since, owing to the orthopositions of the two competing substituents, an intramolecular hydrogen bond, as in 4a, can be formed, which would lead to attack at the position para to the hydroxy group being favoured. Indeed, when sulfur dichloride was slowly added to 2-methoxyphenol (4), in glacial acetic acid, 2,8-dihydroxy- 3,7-dimethoxythianthrene (9) was the predominant product.However, when an excess of sulfur dichloride was added rapidly, mainly 1,6-dichloro-2,7-dihydroxy-3,8-dimethoxythianthrene (10) was formed, i.e.the expected transoid-substituted thianthrene (corresponding to 8), but it is chlorinated in the addition, probably through the equilibrium16 2SCl2mS2Cl2+Cl2. Both compounds were characterized by crystal structure determination. Suitable single crystals in form of the solvate 9.acetone and 10.2THF were measured at 170 K on a CAD4 four-circle diffractometer using Cu-Ka radiation (l=154 and 178 pm) and were corrected for Lorentz and polarization factors.The structures were solved by direct methods.17 Subsequent Fourier syntheses and LSQ calculations18 allowed the positions of all non-hydrogen atoms and, in addition, of the hydrogen atoms at the hydroxy groups to be determined; these atom positions were refined by anisotropic temperature factors. The positions of the other hydrogen atoms were calculated with fixed distances of 96 pm and isotropic temperature factors.The results are summarized in Tables 1, 4 and 5. As is typical for thianthrene derivatives the molecules of 9 and 10 are folded at their SS axes, the angles of fold (defined *To receive any correspondence. Scheme 1 Table 1 Crystal structure parameters for 9.acetone and 10.2THF 9.acetone 10.2THF Empirical formula Crystal system Space group a/pm b/pm c/pm b/° Z Mr V/106 pm3 r/g cmµ3 m/cmµ1 Scan range/° Independent reflections Reflections with |F0|a4s(|F|) Refined parameters R1, R2 C14H12O4S2.C3H6O monoclinic P P21/m 608.4(1) 1384.3(2) 1050.4(2) 103.38(2) 2 366.45 860.6(2) 1.414 29.7 4.5s2ys153 1738 1721 130 0.041, 0.047 C14H10Cl2O4S2.2C4H8O monoclinic P P21/n 1780.1(5) 808.1(2) 1828.8(6) 117.66(2) 4 521.48 2330(1) 1.486 45.2 4.5s2ys153 4298 4266 300 0.057, 0.061J.CHEM. RESEARCH (S), 1997 273 as angles between the normals to the best planes through the aryl rings) being 134.8 and 132.1°, respectively (Figs. 1 and 2). The methoxy and hydroxy substituents are coplanar with the aryl rings to which they belong.Whereas the methoxy group is turned to the outside position, the hydroxy group lies inside forming an intramolecular hydrogen bridge to the oxygen atom of the methoxy group. Owing to steric repulsion the angles OCC (endo) are larger than the corresponding exo ones, the effect being more pronounced for the methoxy groups. In comparison to 9, the introduction of the chloro substituents into 10 causes differentiation of the corresponding angles, especially in the C6 rings (Table 5).All distances lie in the normal ranges (Table 4) and no different influence of the methoxy and hydroxy substituents can be observed, though they differ in their kinetic effects as can be seen from the syntheses of 9 and 10. In the crystals the hydroxy groups also form intermolecular hydrogen bonds to the solvate molecules. In 9.acetone an infinite chain of alternating thianthrene and acetone molecules is formed (Fig. 3) since the oxygen atom of each acetone molecule is involved in two hydrogen bridges. In 10.2THF the crystal is built up by isolated THF...10...THF units. We thank the Fonds der Chemischen Industrie for financial support. Full text in German Techniques used: IR, 1H and 13C NMR, X-ray analysis References: 20 Tables 2 and 3: Atomic coordinates and equivalent isotropic thermal parameters for 9.acetone and 10.2THF Fig. 4: Arrangement of the THF ···10···THF units in the crystal of 10.2THF Schemes 2 and 3: Probable reaction paths leading to 9 and 10 Received, 13th March 1997; Accepted, 23rd April 1997 Paper G/7/02774E References 1 Part 28: S.Friederichs, J. Kudnig and G. Klar, Z. Naturforsch., B: Chem. Sci, 1996, 51, 1295. 2 T. Weiß and G. Klar, Liebigs Ann. Chem., 1978, 785. 4 A. Streitwieser, Jr., P. C. Mowery, R. G. Jesaitis and A. Lewis, J. Am. Chem. Soc., 1970, 92, 6529. 5 W. J. Hehre, L. Radom and J. A. Pople, J. Am. Chem. Soc., 1972, 94, 1496. 16 M. Trautz, Z. Elektrochem., 1929, 35, 110. 17 G. M. Sheldrick, SHELX-86, Programs for Crystal Structure Solutions, University of G�ottingen, 1986. 18 G. M. Sheldrick, SHELX-76, Programs for Crystal Structure Determination, University of Cambridge, England, 1976. Fig. 1 Molecular structure of 9.acetone Fig. 2 Molecular structure of 10.2THF Fig. 3 Infinite chains of alternating thianthrene and acetone molecules in the crystal of 9.acetone Table 4 Relevant bond lengths (pm) in 9.acetone and 10.2THF (mean values) 9.acetone 10.2THF C·Cl C·S Car·O Calk·O (S)C·C(S) (S)C·C (O)C·C (O)C·C(O) O·H O···Hintra O···Hinter · 177.0(2) 135.9(2) 142.3(3) 138.9(3) 139.8(3) 138.3(3) 141.1(3) 86(3) 220 196 173.5(3) 177.0(3) 135.7(4) 143.0(4) 139.7(4) 139.4(5) 138.0(5) 141.2(5) 80(4) 230 189 Table 5 Bond angles (°) in 9.acetone and 10.2THF (mean values) 9.acetone 10.2THF C·S·C C·O·C C·O·H Cl·C·C(S) Cl·C·C(O) S·C·Cendo S·C·C(H)exo S·C·C(Cl)exo O(CH3)·C·Cendo O(CH3)·C·Cexo O(H)·C·Cendo O(H)·C·Cexo C(H)·C(S)·C(S) C(Cl)·C(S)·C(S) C(S)·C(H)·C(O) C(S)·C(Cl)·C(O) C(H)·C(O)·C(O) C(Cl)·C(O)·C(O) O·H···Ointra O·H···Ointer 100.5(1) 117.9(1) 108(2) ·· 120.8(1) 119.4(1) · 125.9(1) 114.3(1) 121.3(1) 119.0(1) 119.9(1) · 120.3(1) · 119.8(1) · 115 150 100.8(1) 117.1(2) 114(2) 120.3(2) 117.7(2) 120.8(2) 118.3(2) 121.3(2) 125.9(3) 113.8(3) 121.4(3) 120.5(3) 118.5(3) 120.1(3) 122.0(3) 120.4(3) 118.6(3) 110 157

ISSN:0308-2342    

DOI:10.1039/a702774e

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Ph OH O Ph O X 1 3 4 5 Ph X OCH2CH2A Z-isomer (b) OCH2CH2A + Ph X E-isomer (a) Ph OH X OCH2CH2A 2a X = S, A = N(CH2CH2)2O b X = Se, A = N(CH2CH2)2O a X = S b X = Se 3 X = S, A = N(CH2CH2)2O 4 X = Se, A = N(CH2CH2)2O i ii 1 iii 274 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 274–275 J. Chem. Research (M), 1997, 1828–1849 Synthesis of Heterocyclic Analogues of Tamoxifen as Potential Antiestrogens Natarajan Srikanth, Choon-Hong Tan, Siu-Choon Ng, Teck-Peng Loh, Lip-Lin Koh and Keng-Yeow Sim* Department of Chemistry, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260 The synthesis of (E/Z)-1-aryl-2-phenyl-1-(2-thienyl/selenophen-2-yl)but-1-enes, derived from 2-phenyl-1-(2-thienyl/ selenophen-2-yl)butan-1-ones, is described; the key steps in the synthesis involve the reaction of the butan-1-ones with 4-(2-morpholinoethoxy)phenyl bromide, followed by dehydration of the resulting carbinols to give the target compounds which are separated by fractional recrystallisation. Non-steroidal antiestrogens of the triarylethylene type, notably Z-tamoxifen, have been widely used as the first line endocrine therapy drugs for the treatment of estrogendependent tumours.It is generally acknowledged that antiestrogens act by competitively inhibiting the binding of estradiol to the estrogen receptor.1 The clinical efficacy of tamoxifen in the treatment of breast cancer has attracted widespread interest in the synthetic and biological studies of antiestrogens.2 For this purpose it is essential that only the geometrical isomer of Z-configuration is used since the E-isomer has unwanted opposing estrogenic properties.3,4 The separation of the mixture of isomers that results from the synthesis is often not easy and the present separation methods of the E–Z mixture5,6 are usually by fractional recrystallisation from a suitable solvent. So far there has been only one report on the synthesis of triarylethylene analogues7 (1,2-diphenyl-1-pyridylbut-1-enes) in which one of the phenyl groups has been replaced by an aromatic heterocyclic ring (pyridine).An E:Z ratio of 1:1 was obtained and only the Z-isomer could be separated by fractional recrystallisation. We report herein the synthesis of (E/Z)-1-aryl-2-phenyl- 1-(2-thienyl/selenophen-2-yl)but-1-enes, derived from 2- phenyl-1-(2-thienyl/selenophen-2-yl)butan-1-ones. It is well known that selenium in the appropriate chemical form and concentration exhibits anticarcinogenic properties in numerous animal tumour model systems.8 The methodology used for the synthesis of (E/Z)-1-aryl- 2-phenyl-1-(2-thienyl/selenophen-2-yl)but-1-enes (3a, 3b, 4b) is depicted in the Scheme.The precursors, 2-phenyl- 1-(2-thienyl/selenophen-2-yl)butan-1-ones (1), were synthesised by the reaction of thiophene/selenophene with 2- phenylbutyric acid in trifluoroacetic anhydride.9 The products of electrophilic substitution at positions 2 and 3 of the 5-membered heterocycles can be differentiated by their 1H NMR data.10 The chemical shifts of 1a, d3 7.71, d4 7.05, d5 7.56 and coupling constants J34 3.83, J35 1.07, J45 4.92 Hz are consistent with the results reported for 2-substituted thiophenes10 (d3 7.80, d4 7.17, d5 7.80 and J34 3.74, J35 1.09, J45 5.07 Hz).Similarly the chemical shifts of 1b, d3 7.93, d4 7.29, d5 8.30 and coupling constants J34 3.98, J35 1.02, J45 5.50 Hz are consistent with the results reported for 2-substituted selenophene10 (chemical shifts d3 8.02, d4 7.43, d5 8.52 and coupling constants J34 3.96, J35 1.14, J45 5.54 Hz).The reaction of the 2-phenyl-1-(2-thienyl/selenophen-2-yl)butan-1-ones (1) with the 4-(2-morpholinoethoxy)phenyl bromide, followed by acid-catalysed dehydration of the tertiary alcohols 2 obtained furnished mixtures of geometric isomers 3 and 4. The E- and Z-isomers of the thiophene analogue, 3a and 3b (E:Z=1:2), could be separated by recrystallisation from methanol. However, only the Z-isomer for the selenium analogue 4b (E:Z=1:4) could be obtained in the pure state by recrystallisation.It is well known that the geometric isomers of the tamoxifen derivatives can be differentiated by their 1H NMR spectra.11 Thus the isomers with monosubstituted aromatic rings (1- and 2-phenyl groups) are readily identified on the basis of the chemical shifts of the AB quartet for the protons of the remaining disubstituted aromatic moiety. In the transisomer (Z-tamoxifen) the AB quartet is usually found at a higher field as a consequence of the combined shielding influence of the two adjacent phenyl rings.On this basis and assuming the heteroaromatic thiophene ring as being equivalent to a phenyl group, compound 3a, with an AB quartet at dH 6.57–6.85 (J 8.85 Hz) and other aromatic protons at dH 6.95–7.26, can be assigned as the E-isomer. Compound 3b, with an AB quartet at dH 6.94–7.23 (J 8.72 Hz) and other aromatic protons at dH 7.24–7.35, can be assigned as the Z-isomer. Further confirmation of these structures was obtained by comparing the chemical shifts of the ethyl and the OCH2 groups with those reported for the E/Z isomers of 1-[-4-(2-dimethylaminoethoxy)phenyl]-2-phenyl-1-(4-pyridyl) but-1-ene and other triarylethylene derivatives.7,12 Thus compound 3a, showing a triplet at dH 1.00 (CH3), a quartet at dH 2.67 (CH2) and a triplet at dH 3.99 (OCH2), is assigned the E-isomer.Compound 3b, showing a triplet at dH 0.87 (CH3), a quartet at dH 2.29 (CH2) and a triplet at dH 4.16 (OCH2), is assigned the Z-isomer. Similarly compound 4 was assigned the Z-configuration based on the above results. The struc- *To receive any correspondence. Scheme Reagents and conditions: i, TFAA, thiophene/ selenophene; ii, n-BuLi, p-BrC6H4OCH2CH2A, THF, µ78 °C; iii, H+, MeOH, room temperatureJ. CHEM. RESEARCH (S), 1997 275 tures of 3a,b have also been confirmed by X-ray diffraction analysis.The X-ray structures of the isomers 3a and 3b are shown in Figs. 1 and 2, respectively. The crystal structure of 3a has monoclinic symmetry. Each asymmetric unit contains one independent molecule. The thiophene ring is disordered to two sets by flipping over around the C(1)·C(1s) bond with site occupancy factors of 0.60 and 0.40. This is possibly due to the free rotation about the C(1)·C(1s) bond. The conformation at the C(1)�C(2) double bond is as follows: (1) bondings at both C(1) and C(2) are planar; (2) the thiophene ring is cis to the ethyl group and (3) the N(CH2CH2)2O ring has a chair conformation.The crystal structure of 3b has orthorhombic symmetry. The thiophene group is again disordered (0.65/0.35). The conformation at the C(1)�C(2) double bond is as follows: (1) bondings at both C(1) and C(2) are planar; (2) the thiophene ring is trans to the ethyl group and (3) the N(CH2CH2)2O ring has a chair conformation.Crystal Data for 3a.·C26H29O2NS, Mr=419.6, monoclinic, a=25.962 (5), b=5.7470 (10), c=31.424 (6) Å, b=97.34 (3)°, V=4650 (2) Å3, DC=1.199 mg mµ3, Z=8, F(000)=1792, m(Mo-Ka)=0.161 mmµ1, space group I2/a. Crystal Data for 3b.·C26H29O2NS, Mr=419.6, orthorhombic, a=30.604 (7), b=51.461 (11), c=5.8030 (10) Å, V=9139 (3) Å3, DC=1.220 mg mµ3, Z=16, F(000)=3584, m(Mo-Ka)=0.163 mmµ1, space group Fdd2. Crystallographic Analyses.·Data were collected on a Siemens R3m/V diffractometer and structures elucidated by direct methods13 and refined by full-matrix least-squares analysis.14 The final R value was 0.060 (Rw=0.089) for compound 3a and 0.039 (Rw=0.036) for compound 3b.A preliminary ligand-binding study of compound 3b (which has the same configuration as E-tamoxifen) on a Molt 4 cell line showed that it had a lower relative binding affinity than Z-tamoxifen. Studies on the bioactivities of the synthetic compounds are in progress.We thank the National University of Singapore for a grant in support of this research and for the award of a Research Scholarship to N. S. Techniques used: IR, 1H NMR, mass spec, elemental analyses, TLC and X-ray diffraction References: 14 Appendix: Tables of atomic coordinates and equivalent isotropic displacement coefficients, bond lengths and angles, anispic displacement coefficients, H-atom coordinates and isotropic displacement coefficients for 3a and 3b Received, 28th February 1997; Accepted, 25th April 1997 Paper E/7/01410D References cited in this synopsis 1 V.C. Jordan, Pharmacol. Rev., 1984, 36, 245. 2 R. A. Magarian, L. B. Overacre, S. Singh and K. L. Meyer, Curr. Med. Chem., 1994, 1, 61. 3 M. J. K. Harper and A. L. Walpole, Nature (London), 1967, 212, 87. 4 V. C. Jordan, B. Hablemann and K. E. Allen, Endocrinology, 1981, 108, 1353. 5 M. J. K. Harper, D. N. Richardson and A. L. Walpole, Br. Pat., 1 064 629, 1966. 6 L. Magdani, A.Hutak, E. Szatmari, I. Simoni, J. Halmos and F. Nemere, Belg. Pat., 892 662, 1982. 7 W. Schwarz, R. W. Hartmann and H. Schonenberger, Arch. Pharm. (Weinheim, Ger.), 1991, 324, 223. 8 G. N. Schrauzer, Selenium in Medicine and Biology, ed. J. Neve and A. Favier, Walter de Gruyter, Berlin, Germany, 1988, p. 251. 9 M. Jarman and R. McCague, J. Chem. Res., 1985, (S) 116; (M) 1342. 10 M. E. H. Nygaard, E. O. Pettersen, J. M. Dornish and R. Oftebro, Invest. New Drugs, 1987, 5, 259. 11 R. McCague, O. Tai Leung and M. Jarman, J. Chem. Soc., Perkin Trans. 2, 1988, 1201. 12 (a) R. McCague and G. Leclercq, J. Med. Chem., 1987, 30, 1761; (b) D. J. Collins, J. J. Hobbs and C. W. Emmens, J. Med. Chem., 1971, 14, 952. 13 G. M. Sheldrick, Crystallographic Computing, ed. G. M. Sheldrick, C. Kruger and R. Goddard, Oxford University Press, Oxford, 1985, 175. 14 G. M. Sheldrick, SHELX-76, A Program for X-ray Crystal Structure Determination, University of Cambridge, England, 1976. Fig. 1 X-Ray crystal structure of the E-isomer of 1[4-(2-morpholino- ethoxy)phenyl]-2-phenyl-1-(2-thienyl)but-1-ene Fig. 2 X-Ray crystal structure of the Z-isomer of 1-[4-(2-morpholino- ethoxy)phenyl]-2-phenyl-1-(2-thienyl)but-1-ene

ISSN:0308-2342    

DOI:10.1039/a701410d

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N X 3 N X N 2 hn hn X a X = NMe2 b X = NH2 c X = OEt 1 X 5 X 6 hn hn X a X = OMe b X = OEt c X = SMe d X = NMe2 4 N 11 9 NMe2 NMe2 10 + N N N NMe2 12 hn NH O N OEt N NH2 Et3O+BF4 – EtOH HOAc 7 1c 1b NH O N OEt D hn N NH2 N NMe2 2c 2b 2a N NH2 1b N NMe2 1a hn hn hn EtOH HOAc HNMe2 8 Et3O+BF4 – 276 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 276–277 J. Chem. Research (M), 1997, 1850–1869 Photoisomerization of 3H-Azepines Robert A. Odum and Bernard Schmall*,3 Department of Chemistry, Brooklyn College of The City University of New York, Brooklyn, NY 11210, U.S.A.Photoelectrocyclization of 3H-azepines substituted in the 2-position with ethoxy, amino, and dimethylamino groups yielded 3-substituted 2-azabicyclo[3.2.0]hepta-2,6-dienes as the only major volatile products, in all cases. An active area of photochemical research has been concerned with the photoisomerization reactions of conjugated double bonds and with the application of orbital symmetry theory for such processes.Photoelectrocyclization reactions have been observed for symmetrical cyclohepta-1,3,5-trienes and 1-azacyclohepta-2,4,6-trienes (1H-azepines). In all cases, only one electrocyclization product could be formed by a symmetry-allowed disrotatory closure. At least two different concerted bicyclic photoproducts are possible with unsymmetrical cyclohepta-1,3,5-trienes and 1H-azepines. However, a number of compounds have exhibited stereoselectivity in the formation of the bicyclic isomers. We have been interested in the photochemistry of 1-azacyclohepta-1,4,6-trienes (3H-azepines). 3H-Azepine itself is unstable. A number of 2-substituted 3H-azepines were known when our investigation was initiated.27,28,33 We were particularly interested in the photochemistry of 2-dimethylamino-3H-azepine,28 2-amino- 3H-azepine27 and 2-ethoxy-3H-azepine. Our studies showed that these compounds underwent selective photoelectrocyclization to 3-substituted 2-azabicyclo[3.2.0]hepta-2,6-dienes. Since our work was completed, further syntheses of 2-substituted 3H-azepines have been reported.Surprisingly, there has been only one additional example on the photoelectrocyclization of 2-substituted 3H-azepines to the 3-substituted azabicyclo[3.2.0]heptadiene. 2-Diethylamino-3H-azepine was isomerized to 3-diethylamino-2-azabicyclo[3.2.0]hepta- 2,6-diene in agreement with the selectivity exhibited by 2-dimethylamino-3H-azepine (1a). Concise reviews on the photochemistry of azepines have appeared.Although a preliminary account of our work has been given,55 full details of the syntheses have not been reported. Direct irradiation of dilute pentane solutions of 2-dimethylamino-3H-azepine (1a), 2-amino-3H-azepine (1b) and 2-ethoxy-3H-azepine (1c) with medium-pressure mercury lamps gave the corresponding 3-substituted 2-azabicyclo[3.2.0]hepta-2,6-dienes 2.55 Product yields were determined by GC analysis and were based on reactant consumed.Highest yields were obtained when pentane was employed as solvent and the azepines were irradiated at wavelengths corresponding to their maximum absorptions in the ultraviolet. Reaction solutions were purged of oxygen prior to irradiation. Irradiation of 1a–c gave 2a–c in 70, 50 and 60% yields, respectively. Although there were some uncharacterized products formed in the reactions, they do not alter the basic observation of selectivity in the photoisomerization of the 3H-azepines 1a–c to 2a–c because the minor compounds were formed in very small amounts.3 On the basis of elemental and spectroscopic (UV, IR, 1H NMR) evidence compounds 2a–c can be unequivocally assigned to the photoproducts of the 3H-azepines 1.The structural assignments for compounds 2a–c are supported by chemical transformations (Scheme 4). Although photoelectrocyclization reactions of the unsymmetrical 3H-azepine system can lead to the corresponding 5-substituted 6-azabicyclo[3.2.0]hepta-2,6-dienes 3 by orbital symmetry-allowed disrotatory processes, selectivity in the photoisomerization of the 3H-azepines 1 was observed, and the only major products were the 3-substituted 2-azabicyclo- [3.2.0]hepta-2,6-dienes 2 (Scheme 1).Conrotatory closure leading to azanorcaradiene structures should be sterically unfavourable. Sigmatropic rearrange- *To receive any correspondence. Current Address: National Institutes of Health, PET Department, Building 10, Room 1C-401, Bethesda, MD 20892.E-mail: Schmall@nmdhst.cc.nih.gov. Scheme 1 Scheme 2 Scheme 3 Scheme 4J. CHEM. RESEARCH (S), 1997 277 ment products should be unimportant since the 3H-azepine structure is the more stable tautomer.27 The selectivity of the 3H-azepines is different from that observed in the photoisomerization reactions of cyclohepta-1,3,5-trienes 4 (Scheme 2) with electron-donating substituents in the 1-position of the seven-membered ring.These unsymmetrical cycloheptatrienes have been observed to photoisomerize selectively to 5-substituted bicyclo[3.2.0]hepta-2,6-dienes 5 in direct contrast to the mode of reaction of the 3H-azepines 1, their heterocyclic analogues. A few percent of the 3-substituted bicyclo[3.2.0]hepta-2,6-dienes 6 may have escaped detection, and in fact, in the case of the dimethylamino isomer 4d, about 3% of 6d was observed. Photoelectrocyclization reactions of 3H-azepines 1 should be disrotatory processes, but the reasons for their observed selectivity are unknown. We have made the simple suggestion55 that in order to avoid the loss of resonance energy the preferred pathway for the amidine or imidate ester systems is that leading to the corresponding 3-substituted 2-azabicyclo- [3.2.0]hepta-2,6-dienes 2.The direction of the photo-ring closure of unsymmetrical cycloheptatrienes to bicyclo- [3.2.0]heptadienes may be controlled by the electronic nature of the substituent and the charge distribution in the excited state. However, this concept is not useful for the electrocyclization reactions of 3H-azepines.A reactivity index that predicts the site selectivity in the photocyclization of cycloheptatrienes has been derived by considering the energy change in the excited state. However, site selectivity predictions are inconsistent with experimental observations in unsymmetrical 1H-azepine systems, and have not been applied to the 3H-azepine system.Electrostatic considerations and extended Huckel calculations have been used to allow a choice between two symmetry-allowed pathways in the photochemical ring closure of 1-substituted cycloheptatrienes to bicyclo[3.2.0]heptadienes. However, arguments based on the direction of polarization of the excited state of the 3H-azepines leads to consideration of two extreme dipolar states. Unlike the case of 1-methoxycycloheptatriene, both states are stabilized.Therefore, the formation of both 2 and 3 may be expected from photolysis of 1. In agreement with our simple explanation, the failure to observe the formation of 3 may be due to the preferential excitation to the dipolar state in which the resonance stabilized amidine and imidate ester functions are maintained. Another simple explanation is that formation of 5-substituted 6-azabicyclo[3.2.0]hepta-2,6-dienes 3 involves a 1-azetine structure which may be potentially unstable. However, 1-azetine itself has been prepared and thermally transformed to 2-azabutadiene.The thermal ring opening of 1-azetine to 2-azabutadiene has been predicted by molecular orbital theory to proceed along a pathway similar to that for hydrocarbon analogues. The simple HMO method predicts that introduction of nitrogen atoms into butadiene and hexatriene should not cause any important perturbation in the course of electrocyclic reactions. Thus, 2-azabutadiene should react conrotatorily in a thermal reaction and disrotatorily upon photochemical excitation.Similar conclusions may also be drawn from a detailed all valence-electron calculation of the CNDO/2 or extended Huckel type. Although a number of 1-azetines have been reported in non-photolytic reactions, they have been observed only as intermediates or unstable products in light-induced electrocyclization reactions. Thus, 1-azetines have been prepared by irradiation of a dihydro- 3H-azepine to an unstable azetine structure which was not isolated, and is the postulated intermediate 12 in the irradiation of 2-dimethylamino-4,5-dihydro-3H-azepine (9) to an eneamine 10 and pyrimidine 11 (Scheme 3).75 In these reactions, however, an alternative electrocyclization reaction path did not exist and the formation of the 1-azetine structure demonstrates that without this alternative reaction path the loss of amidine resonance energy does occur.Therefore, although a 1-azetine structure may potentially be formed, albeit photochemically unstable, the observed selectivity in the photoisomerization of the 3H-azepines 1 may be due to preservation of amidine or imidate ester resonance energy.The full paper gives complete synthetic and spectroscopic details on the photoisomerization reactions of the 3H-azepines 1, which have not been previously reported. In addition, this paper reports an unexpected transformation of an amidine to an imidate ester which was observed during this investigation.In order to obtain pure 2-ethoxy-3H-azepine 1c for photochemical studies, the possibility of transforming amidines into imidate esters was investigated. Whereas there was ample precedent for the alcoholysis of imidate esters, the isolation of an imidate ester from the reaction of an amidine with an alcohol was unknown. The conversion of 1b and 2b to the corresponding imidate esters 1c and 2c in absolute ethanol was effected in the presence of a catalytic amount of glacial acetic acid.The possibility that orbital symmetry considerations could rationalize the direction of closure of the 3H-azepines 1 and unsymmetrical cyclohepta-1,3,5-trienes 4 is given elsewhere,3 where the concept is developed that, ‘given an orbital symmetry scheme’, orbital symmetry considerations can account for the direction of closure of unsymmetrical seven-membered ring systems without invoking steric or charge distribution arguments. Techniques used: UV, IR, 1H NMR, GC, polarimetry References: 90 Received, 10th April 1997; Accepted, 12th April 1997 Paper E/7/02465G References cited in this synopsis 3 Abstracted in part from the PhD Thesis of Bernard Schmall, The City University of New York, NY, Photoisomerization of 3HAzepines, Dissertation Abstracts International B, 1972, 33, 1060B, Avail. Univ. Microfilms, Ann Arbor, MI, Order No. 72–24; 248 pp, From Diss. Abst. Int. B, 1972, 33, 1060B. 27 von E. W. Doering and R. A. Odum, Tetrahedron, 1966, 22, 81, and pertinent references cited therein. 28 R. A. Odum and M. Brenner, J. Am. Chem. Soc., 1966, 88, 2074. 33 R. A. Odum and A. M. Aaronson, J. Am. Chem. Soc., 1969, 91, 5680. 55 R. A. Odum and B. Schmall, J. Chem. Soc., Chem. Commun., 1969, 1299. 75 E. Lerner, R. A. Odum and B. Schmall, J. Chem. Soc., Chem. Commun., 1973, 327.

ISSN:0308-2342    

DOI:10.1039/a702465g

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

O O 1 NBS (1 equiv.), H2SO4 (1 drop), MeOH 0 °C then room temp; 12 h, 85% (A:B = 60:40) O O 2a (isomer A) OMe Br + O O 2b (isomer B) Br MeO R O [CH2] n R1 R2 O R O [CH2] n O R1 R2 OMe Br R O [CH2] n O R1 R2 Br MeO isomer A isomer B + NBS, MeOH H2SO4 (1 drop), 0 °C then room temp. 278 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 278–279 J. Chem. Research (M), 1997, 1901–1916 Selective Side-chain Halogenoalkoxylation of Unsaturated (Meth)acrylic Esters Yves Fort* and Christine Gottardi-Dubosclard Laboratoire de Chimie Organique 1, URA CNRS 457, INCM, Facult�e des Sciences, Universit�e Henri Poincar�e - Nancy 1, BP 239, 54506 Vandoeuvre les Nancy cedex, France A convenient preparation of new halogenoalkoxylated methacrylates is described by selective side-chain halogenoalkoxylation of unsaturated methacrylic esters.As part of our ongoing interest in industrial (meth)acrylic esters,3–6 we needed an easy and economical route to bifunctional monomers which possibly could be useful intermediates in the synthesis of many polyfunctional derivatives.In this context, halogenoalkoxylation of unsaturated (meth)acrylates appeared attractive. This reaction has been successfully used in the synthesis of methoxybromide adducts from olefins7–11 but has never been described with polyolefinic compounds such as side-chain unsaturated (meth)acrylates. Here we report the selective preparation of some halogenoalkoxylated methacrylic esters.The halogenoalkoxylation was firstly investigated with the industrially available prop-2-enyl 2-methylprop-2-enoate (1), commonly called allyl methacrylate, which is probably the best model in order to study selective electrophilic functionalisation. 3 In exploratory experiments under classical conditions using bromine and methanol, treatment of 1 failed to give the bromomethoxylated adducts, giving rise to degradation of the starting material. We then changed to favourable conditions7–9 for the liberation of bromonium ions such as acidic conditions.10 Upon treatment with N-bromosuccinimide and a catalytic amount of sulfuric acid in methanol at room temperature, 1 was selectively converted to a mixture of the expected methoxy bromide derivatives 2a and 2b in 85% isolated yield (Scheme 1).As far as the regioselectivity of the reaction is concerned, Markovnikoff’s rule predicts the major formation of the isomer 2b. However this rule fails when electronic and steric effects intervene.14 In particular with allyl methacrylate (1), the formation of isomer 2a must be allowed both by the steric hindrance of the methacrylic part and still more by the µI effect of the ester group.The 2a:2b ratio was determined as 60:40 on the basis of the 400 MHz 1H NMR spectra obtained from the isolated mixture. It may thus be concluded that the major isomer 2a results from an anti-Markovnikoff addition favoured by the inductive and steric effects of the ester group.It must be noted that the absence of rearranged products in addition to 1 allows the direct neighbouring group participation observed in other electrophilic additions to allylic esters15,16 to be ruled out. To investigate further the participation of the ester in the product ratio obtained, we carried out several reactions with allylic acrylate and homologues or with methylated analogues of 1. The results are shown in Table 1. It first appeared that addition to allyl acrylate (entry 2) proceeds with the same regiochemistry as that obtained with 1.This observation allowed us to conclude that the steric effect of the (meth)acrylic moiety is weak. On the other hand, entries 3 and 4 showed that an extra methyl substituent on the unsaturated side-chain has a large effect on the regioselectivity of the reaction. The addition to 2-methylprop-2-enyl methacry- *To receive any correspondence (e-mail: Yves.Fort@lco1.unancy.fr). Scheme 1 Table 1 Selective bromomethoxylation of unsaturated (meth)acrylatesa Substrate Entry R n R1 R2 t/h Yield (%)b A:Bc 1234567 Me H Me Me Me Me H 1111288 HH Me HHHH HHH Me HHH 12 15 15 15 15 15 24 85 78 76 63 80 77 70 60:40 57:43 5:95 88:12 55:45 33:67 30:70 aReactions performed on a 10 mmol scale. Satisfactory spectroscopic data (1H and 13C NMR, IR, MS) were obtained. bIsolated yields by flash chromatography (purity up to 98% determined by 1H NMR and GC analyses.) cDetermined by 400 MHz 1H NMR spectroscopy and confirmed by derivatization.O O O O OR X NXS, ROH H2SO4 cat., (CCl4), 0 °C then room temp.O O X OR isomer A isomer B + J. CHEM. RESEARCH (S), 1997 279 late (entry 3) provided almost exclusively the methoxybromide derivative expected on the basis of carbonium ion stability while the addition to crotyl methacrylate led to an increase in the anti-Markovnikoff selectivity (entry 4). In the case of the homoallylic methacrylate (entry 5), only a weakly diminished effect of the ester moiety was observed leading to a 55:45 isomer ratio.Surprisingly, when the methacrylic or acrylic group is further removed from the double bond (entries 6 and 7) the anti-Markovnikoff adduct was obtained in a larger proportion although there are no longer any inductive effects. This led us to postulate that an w-assistance between the carbonyl group and the intermediate bromonium or carbonium ion exists. These results show the influence of the (meth)acrylic moiety on the functionalisation of the ester side-chain. Such an influence is not unique to bromomethoxylation but can be compared to other nucleophilic substitutions of a halogen atom on the esterifying chain.4–6 We next examined routes to other halogenoalkoxylated methacrylates, the results of which are shown in Table 2.These results clearly indicated that: (i) iodo- and chloromethoxylated derivatives of 1 can easily be obtained (entries 1 and 2).The reaction of N-chlorosuccinimide required 60 °C to work. In entry 1, the selectivity is weakly affected showing the effect of the steric hindrance on the attack of the nucleophile; (ii) primary and secondary alcohols (entries 3–8) were effective in the addition while tertiary alcohols (entry 9) were probably too sterically hindered to attack the intermediate bromonium ion. This hypothesis is in accordance with the results obtained with secondary alcohols where the regiochemical outcome was more oriented towards the anti-Markovnikoff addition product (entries 6–8); (iii) some functional alcohols may be introduced (entries 10–14).Particularly interesting were the reactions of 2-chloroethanol and 3-chloropropanol leading to dihalogenated derivatives (entries 10 and 11). In conclusion, we have shown that halogenoalkoxylated (meth)acrylic monomers can easily be obtained by selective electrophilic functionalisation of side-chain unsaturated methacrylates.The regioselectivity of the addition was influenced by steric and above all by electronic effects due to the (meth)acrylic part of the monomer. These results are the second example we have found of these particular interactions governing the functionalisation of (meth)acrylic monomers. Techniques used: 1H and 13C NMR, IR, CI-MS, elemental analysis References: 18 Schemes: 3 Figures: 2 Received, 5th November 1996; Accepted, 6th May 1997 Paper E/6/07529K References cited in this synopsis 3 Y.Fort, A. Olszewski-Ortar and P. Caubere, Tetrahedron, 1992, 48, 5099. 4 M. C. Berthe, Y. Fort and P. Caub`ere, Synth. Commun., 1992, 22, 617. 5 C. Dubosclard-Gottardi, P. Caubere and Y. Fort, Tetrahedron, 1995, 51, 2561. 6 C. Dubosclard-Gottardi and Y. Fort, Synth. Commun., 1995, 25, 3173; 1996, 26, 2811. 7 C. Guss and R. Rosentahl, J. Am. Chem. Soc., 1955, 77, 2549. 8 W. H. Puterbaugh and M. S. Newman, J. Am. Chem. Soc., 1957, 79, 3469. 9 V.L. Heasley, R. A. Skidgel, G. E. Heasley and D. Strickland, J. Org. Chem., 1974, 39, 3953. 10 V. L. Heasley, K. E. Wade, T. G. Aucoin, D. E. Gipe and D. F. Shellhammer, J. Org. Chem., 1983, 48, 1377. 11 P. L. Anelli, A., Beltrami, M. Lolli and F. Uggeri, Synth. Commun., 1993, 23, 2639. 14 D. R. Dalton, V. P. Dutta and D. C. Jones, J. Am. Chem. Soc., 1968, 90, 5498. 15 S. Winstein and L. Goodman, J. Am. Chem. Soc., 1954, 76, 436Z. K. M. Abd El Samii, M. I. Al Ashmawy and J. M. Mellor, Tetrahedron Lett., 1986, 27, 5289. Table 2 Bromoalkoxylation of allyl methacrylate (1)a Entry X ROH (equiv.b) t/h Yield (%)c A:Bd 123456789 10 11 12 13 14 Cl I Br Br Br Br Br Br Br Br Br Br Br Br MeOH (solvent) MeOH (solvent) EtOH (solvent) BunOH (solvent) n-C10H23OH (10) PriOH (solvent) c-C6H11OH (10) norborneol (10) ButOH (solvent) Cl[CH2]2OH (10) Cl[CH2]3OH (10) Me[(OCH2)2]2OH (10) H[(O(CH2)2]2OH (10) glycerol (10) 50e 2.5 12 24 72 72 62 48 144 48 48 24 24 5 60 80 80 75 75 74 44 59 19f 50 62 83 62g 48g 52:48 58:42 57:43 56:44 58:42 65:35 65:35 66:34 n.d.h 59:41 56:44 58:42 57:43 61:39 aReactions performed on a 10 mmol scale. Satisfactory spectroscopic data (1H and 13C NMR, IR, MS) were obtained. bCCl4 (20 mL) was used as solvent when 10 equiv. of alcohol were used. cIsolated yields by flash chromatography (purity up to 98% determined by 1H NMR and GC analyses). dDetermined by 400 MHz 1H NMR spectroscopy. eReaction performed at 60 °C. f48% Conversion. gYields in mono-adducts. hn.d.=not determined.

ISSN:0308-2342    

DOI:10.1039/a607529k

出版商:RSC    

年代:1997

数据来源: RSC

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N N O H X O H H 1 2 3 4 5 6 X = H X = OH X = Me X = F X = Cl X = Br X = I I II III IV V VI VIII 280 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 280–281 J. Chem. Research (M), 1997, 1917–1928 Binary and Ternary Interactions of Mercury(II) with Seven Pyrimidines and Ethylenediaminetetraacetic Acid Jos�e Louis Lucas Vaz,a Tayeb Atbir,b Abdallah Albourineb and Michelle Petit- Ramel*a aLaboratoire de Chimie Analytique II - LICAS, Universit�e Claude Bernard - Lyon 1, 43, boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France bLaboratoire de Chimie Physique, D�epartement de Chimie, Facult�e des Sciences, Universit�e Ibnou Zohr, BP 2810 Agadir, Morocco The introduction of an electronegative substituent at the C-5 position of a uracil ring leads to a decrease in the ring’s complexation constants; the formation of mixed ligand complexes of mercury(II) takes place above pH 6 and gives [Hg(edta)(thymine)]-type species, the mixed coordination of which leads to enhanced stability.It is well known that the metal complexes of pyrimidines and their nucleotides play a dominant role in many biochemical systems.6,8 The present paper reports a study of the stability of mercury(II) complexes in aqueous solution with seven pyrimidines of biological interest. Our contribution tries to quantify the influence on the stability constants of the C-5 substitution on the one hand and the stability of the ternary complexes formed with thymine or uracil in the presence of ethylenediaminetetraacetic acid (edta) on the other hand.Protometric studies on the pyrimidine analogues studied in the present work were performed according to the procedure previously described9,10 by the usual approach of varying the ratio of total ligand to total metal concentration. Measurements were carried out at 25 °C and at a constant ionic strength of 0.1 M (NaNO3), under a dynamic nitrogen atmosphere in order to avoid oxidation of the ligands. The acidity constants of the seven ligands had been determined previously12 and the acid enhancement effect of the uracil halogenation was demonstrated.The complexation between a metal ion M and the two ligands L and Lp can be described by the general equilibrium: pM+qH+rLsLpmMpHqLrLps bpqrs= [MpHqLrLps] [M]pÅ[H]qÅ[L]rÅ[Lp]s For simplicity, the charges of the species are omitted. The equilibrium constants bpqrs were calculated by a method using the average number of H+ ions bound per mole of ligand, �q, and a least-square refinement between the calculated average number of H+ ions bound per mole of ligand, �qcal, and the *To receive any correspondence.Table 1 Logarithms of the protonation and stability constants of the mercury(II)–pyrimidine systems (T=25 °C and I=0.1 M NaNO3) Ligand (L) pqrs log bpqrs Species pH uracil (I) 0 1 1 0 1 µ1 1 0 1 µ1 2 0 9.17�0.0112 2.17�0.04 6.05�0.08 [HgHµ1(L)] [HgHµ1(L)2]µ 6spHs12 8spHs12 isobarbituric acid (II) 0 1 1 0 1 µ1 1 0 1 µ1 2 0 8.12�0.0112 1.98�0.04 5.88�0.08 [HgHµ1(L)] [HgHµ1(L)2]µ 6spHs12 8spHs12 thymine (III) 0 1 1 0 1 µ1 1 0 1 µ1 2 0 9.56�0.0112 2.25�0.04 6.32�0.08 [HgHµ1(L)] [HgHµ1(L)2]µ 6spHs12 8spHs12 5-fluorouracil (IV) 0 1 1 0 1 µ1 1 0 1 µ1 2 0 7.86�0.0112 1.49�0.03 4.92�0.07 [HgHµ1(L)] [HgHµ1(L)2]µ 5spHs12 7spHs12 5-chlorouracil (V) 0 1 1 0 1 µ1 1 0 1 µ1 2 0 7.80�0.0112 1.42�0.03 4.81�0.06 [HgHµ1(L)] [HgHµ1(L)2]µ 5spHs12 7spHs12 5-bromouracil (VI) 0 1 1 0 1 µ1 1 0 1 µ1 2 0 7.83�0.0112 1.55�0.03 5.01�0.08 [HgHµ1(L)] [HgHµ1(L)2]µ 5spHs12 7spHs12 5-iodouracil (VII) 0 1 1 0 1 µ1 1 0 1 µ1 2 0 7.92�0.0112 1.62�0.04 5.12�0.08 [HgHµ1(L)] [HgHµ1(L)2]µ 5spHs12 7spHs12J. CHEM.RESEARCH (S), 1997 281 experimental average number of H+ions bound per mole of ligand, �qexp. Mercury(II)–pyrimidine systems. These systems were studied with low metal concentrations between 1.42 and 2.5Å10µ5 M with corresponding ligand to metal ratios of 4–7:1.In the acidic medium, the equilibrium constants (Table 1) were calculated by considering the presence of the [HgHµ1] species (=HgOH). From Table 1, it can be seen that the substitution of the uracil hydrogen atom in the C-5 position by a more electronegative substituent causes a decrease in the complex stability. Mercury(II)–edta system. In order to ensure the homogeneity of our study, we determined the protonation equilibrium constants of edta and complexation equilibrium constants of the mercury(II)–edta system under the same conditions of temperature, ionic strength and concentration of ligand.The results, in good agreement with the bibliographic data, are summarised in Table 2. As expected, edta has a greater complexing ability than pyrimidine bases. Mercury(II)–edta–pyrimidine base systems. The ternary systems showed the presence of the [Hg(edta)(thymine)] and [Hg(edta)(uracil)] ternary complexes (Fig. 4) in addition to [Hg(Hedta)] and [Hg(edta)] binary complexes.[HgHµ1 (uracil)], [HgHµ1(uracil)2], [HgHµ1(thymine)] and [HgHµ1 (thymine)2] were not present in the ternary systems. By comparison of the stability constants of the ternary and binary systems, it is demonstrated that ternary complexation is responsible for the stabilisation of the mixed complexes. Full text in French Techniques used: Protometry References: 15 Figures: 4 Received, 10th January 1997; Accepted, 30th April 1997 Paper F/7/03085A References cited in this synopsis 6 T.Itahara, T. Yoshitake and A. Nishino, Bull. Chem. Soc. Jpn., 1994, 67, 2257. 8 V. Noskov, A. Matsuda and H. Hayatsu, Mutation Research, 1994, 308, 43. 9 A. Albourine, M. Petit-Ramel, G. Thomas-David and J. J. Vallon, Can. J. Chem., 1989, 67, 959. 10 J. L. Lucas Vaz, G. Duc, M. Petit-Ramel, R. Faure and O. Vittori, Can. J. Chem., 1996, 74, 359. 12 J. L. Lucas Vaz, T. Atbir, A. Albourine and M. Petit-Ramel, Analysis, 1996, 24, 303. 13 G. Anderegg, Critical Survey of Stability Constants of EDTA Complexes, no. 14, part A, Pergamon Press, Oxford, 1977. 14 M. Petit-Ramel, G. Thomas-David, G. Perichet and P. Pouyet, Can. J. Chem., 1984, 62, 22. Fig. 4 Distribution curves for the mercury(II)–edta–thymine system: CM\5Å10µ5 M and CL\10µ4 M. The relative concentration of each species is given as a percentage of the total mercury(II) concentration CM. Table 2 Protonation equilibrium and formation constants of the mercury(II)–pyrimidine and mercury(II)–edta–pyrimidine bases systems (T=25 °C and I=0.1 M NaNO3) System pqrs log bpqrs (lit.) pH H4edta H3edta H2edta Hedta 0 4 0 1 0 3 0 1 0 2 0 1 0 1 0 1 21.33�0.08 (21.38�0.1813) 19.03�0.04 (19.18�0.0513) 16.29�0.02 (16.41�0.0213) 10.07�0.02 (10.25�0.0213) s3,5 1spHs5 2spHs9 a8 [HgHµ1]+ [Hg(Hedta)]µ [Hg(edta)]2µ 1 µ1 0 0 1 1 0 1 1 0 0 1 µ3.3�0.2 (µ3.1�0.114) 23.8�0.2 (24.3�0.113) 20.4�0.2 (21.6�0.113) s5 a2 [Hg(edta

ISSN:0308-2342    

DOI:10.1039/a703085a

出版商:RSC    

年代:1997

数据来源: RSC

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R2 R1 H 1 R1 = H, R2 = O 2 R1 = OH, R2 = a-H, 17b-OAc OH R1 H R1 R1 = H R1 = OH HO R1 = H R1 = OH not detected (13) OH HO (29) OH HO (8) OH OH OH R1 H R1 R1 = H R1 = OH (35) not detected R1 = H R1 = OH (17) not detected OH (20) OH (30) HO HO HO HO + + + + a-addition b-addition a-addition b-addition (28) (18 as 17b-acetate) (40 as 17b-alcohol) + 3 HO 282 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 282–283† Regio- and Stereo-chemical Effects in the Hydroboration of D2-Steroidal Allylic and Homoallylic Alcohols† James R.Hanson,* Mansur D. Liman and Sivajini Nagaratnam School of Molecular Sciences, University of Sussex, Brighton, Sussex BN1 9QJ, UK A comparison between the hydroboration of D2-steroidal 1a-allylic and 5a-homoallylic alcohols reveals that whereas both have a stereochemical directing effect, only the allylic alcohol modifies the regiospecificity of the reaction. An allylic hydroxy group has a significant effect on the products that are formed from an alkene by hydroboration and oxidation with alkaline hydrogen peroxide.1–3 In cyclic systems a significant proportion of the addition takes place adjacent and trans to the hydroxy group of the allylic alchol.4 These effects on regioselectivity may compete with the normal stereochemical directing effects of the steroid carbon skeleton.5,6 In order to evaluate the relative significance of electronic and steric contributions, we compared the results of hydroboration of the a-oriented axial allylic alcohol, 17b-acetoxy-1a-hydroxy-5a-androst-2-ene (2) and the a-oriented axial homoallylic alcohol, 5a,17b-dihydroxy- 5a-androst-2-ene (3).In both cases the axial hydroxy group is trans to the sterically directing 10b-methyl group. The substrates were prepared by literature methods.7,8,9 The hydroboration and oxidation reactions were carried out using 1 M borane in tetrahydrofuran followed by oxidation with alkaline hydrogen peroxide.The products were separated by chromatography on silica and the results are shown in Fig. 1. The structures of the products were established from the multiplicity of the CH(OH) resonances in the 1H NMR spectrum10 and by comparison with literature data.11 The axial 2b-H of 2a,17b-dihydroxy- and 2a,5a,17b-trihydroxy- 5a-androstane appeared as a triplet (J 10.9 Hz) of triplets (J 4.6 Hz) indicative of two diaxial and two axial:equatorial couplings. In 17b-acetoxy-1a,2a-dihydroxy-5a-androstane and the corresponding triol, the 2b-H (dH 3.82 and 3.85 respectively) appeared as a doublet (J 10.9 Hz) of doubledoublets (J 2.9 and 5.2 Hz).The 1b-H of the 17b-acetate was a doublet (dH 3.66, J 2.9 Hz). The smaller 1b:2a-coupling constant is probably indicative of a slightly different conformation of ring A brought about by hydrogen bonding in the 1:2 glycol. The equatorial 2a-H signals were broad singlets. The 3a,17b- and 3b,17b-dihydroxy- and 3a,5a,17b- and 3b,5a,17b-trihydroxy-5a-androstanes were known compounds. 11–13 *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Fig. 1 Yields (%) of hydroboration products of androst-2-enesJ. CHEM. RESEARCH (S), 1997 283 The influence of the allylic hydroxy group on the regiochemistry of the reaction can be seen in the increased proportion of hydroboration of 17b-acetoxy-1a-hydroxy-5a-androst- 2-ene at C-2 compared to the unsubstituted case.However the potential 1:3-diaxial interaction with the 10b-methyl group reduces the trans directing effect of the hydroxy group. On the other hand the homoallylic 5a-hydroxy group had relatively little effect on the position of the hydroboration but increased the proportion of b-face addition possibly through the formation of bulky borate esters on the a-face of the molecule.Experimental General experimental details have been described previously.5 The steroids were crystallized from ethyl acetate or acetone:light petroleum mixtures. 5a-Androst-2-en-17-one (1) had mp 107–108 °C (lit.,7 108–109 °C). 17b-Acetoxy-1a-hydroxyandrost- 2-ene, prepared by the treatment of 17b-acetoxy-1a,2a-epoxyandrostan- 3-one with hydrazine hydrate,8 had mp 131– 133 °C (Found: C, 75.4; H, 9.8. C21H32O3 requires C, 75.9; H, 9.7%), vmax/cmµ1 3510, 1734; dH (CDCl3) 0.72 (3 H, s, 18-H), 0.81 (3 H, s, 19-H), 2.04 (3 H, s, OAc), 3.71 (1 H, brs, 1b-H), 4.59 (1 H, t, J 8 Hz, 17a-H), 5.87 (2 H, s, 2- and 3-H). 5a,17b-Dihydroxyandrost-2-ene had mp 171–173 °C (lit.,9 171–172 °C). Hydroboration Experiments.·(a) 5a-Androst-2-en-17-one (1) (1 g) in dry THF (30 cm3) was treated with 1 M borane in THF (20 cm3) under nitrogen at 0 °C for 4 h. Water (10 cm3) was added and the solution was cooled. Aqueous 10% sodium hydroxide (20 cm3) was added followed by the dropwise addition of 30% hydrogen peroxide (30 cm3).The mixture was stirred overnight. Sodium sul- fite (2 g) was added followed by acetic acid (1 cm3), water (50 cm3), dil. hydrochloric acid (100 cm3) and ethyl acetate (100 cm3). The mixture was stirred for a further 15 min. The organic phase was separated, washed with water, brine and dried. The solvent was evaporated to give a residue which was chromatographed on silica. Elution with 25% ethyl acetate:light petroleum gave 3a,17b-dihydroxy- 5a-androstane (370 mg), prisms, mp 221–223 °C (lit.,11 222–224 °C).Elution with 28% ethyl acetate:light petroleum gave 3b,17b-dihydroxy-5a-androstane (180 mg), needles, mp 167– 169 °C) (lit.,11 168 °C). Further elution with 30% ethyl acetate:light petroleum gave 2a,17b-dihydroxy-5a-androstane (302 mg), needles, mp 172–174 °C (Found: C, 77.7; H, 11.0. C19H32O2 requires C, 78.0; H, 11.0%), vmax/cmµ1 3490, 3382; dH (CDCl3) 0.73 (3 H, s, 18-H), 0.80 (3 H, s, 19-H), 3.63 (1 H, t, J 8.6 Hz, 17a-H), 3.77 (1 H, tt, J 4.6 and 10.9 Hz, 2b-H).(b) 17b-Acetoxy-1a-hydroxy-5a-androst-2-ene (2) (600 mg) in dry THF (20 cm3) was treated with 1 M borane in THF (14 cm3) and oxidized with aqueous sodium hydroxide and hydrogen peroxide as above. The product was chromatographed on silica. Elution with 20% ethyl acetate:light petroleum gave 17b-acetoxy-1a,2a-dihydroxy- 5a-androstane (110 mg), needles, mp 113–114 °C (Found: C, 68.7; H, 9.5.C21H34O4 requires C, 68.7; H, 9.8%), vmax/cmµ1 3512, 1732; dH (CDCl3) 0.77 and 0.78 (each 3 H, s, 18- and 19-H), 2.03 (3 H, s, OAc), 3.66 (1 H, d, J 2.9 Hz, 1b-H), 3.82 (1 H, ddd, J 2.9, 5.2 and 10.9 Hz, 2b-H), 4.56 (1 H, t, J 8.2 Hz, 17a-H). Irradiation of the signals at dH 0.77 and 0.78 caused an nOe enhancement of the resonances at dH 3.66 (3.1%) and 3.82 (6.5%). Further elution gave 1a,2b,17b-trihydroxy-5a-androstane (80 mg), needles, mp 152–155 °C (Found: C, 71.5; H, 10.6.C19H32O3.0.5H2O requires C, 71.8; H, 10.5%), vmax/cmµ1 3340; dH (CDCl3) 0.74 (3 H, s, 18-H), 0.77 (3 H, s, 19-H), 3.65 (1 H, t, J 8.2 Hz, 17a-H), 3.74 (3 H, s, 1b-H), 4.11 (1 H, brs, 2a-H). Irradiation of the signal at dH 0.77 produced an nOe enhancement of the signal at dH 3.74 (1.9%). Further elution gave 1a,2a,17b-trihydroxy-5a-androstane (240 mg), needles, mp 140–142 °C (Found: C, 71.4; H, 10.3. C19H32O3.0.5H2O requires C, 71.8; H, 10.5%), vmax/cmµ1 3210; dH (CDCl3) 0.74 (3 H, s, 18-H), 0.79 (3 H, s, 19-H), 3.64 (2 H, m, 1b- and 17a-H), 3.85 (1 H, ddd, J 2.9, 5.2 and 10.9 Hz, 2b-H).(c) 5a,17b-Dihydroxyandrost-2-ene (1.2 g) was treated with 1 M borane in THF (20 cm3) and oxidized with aqueous sodium hydroxide and hydrogen peroxide as above. The products were separated by chromatography on silica. Elution with 30% ethyl acetate:light petroleum gave 3a,5a,17b-trihydroxyandrostane (251 mg), plates, mp 193–195 °C (lit.,12 194–196 °C).Further elution gave 2b,5a,17b-trihydroxyandrostane (105 mg), needles, mp 207–209 °C (Found: C, 70.0; H, 11.0. C19H32O3.H2O requires C, 69.9; H, 10.5%), vmax/cmµ1 3499, 3391, 3320; dH (CDCl3) 0.74 (3 H, s, 18-H), 1.21 (3 H, s, 19-H), 3.65 (1 H, t, J 8.5 Hz, 17a-H), 4.18 (1 H, brs, 2a-H). Elution with 32% ethyl acetate:light petroleum gave 2a,5a,17b-trihydroxyandrostane (368 mg), prisms mp 201–202 °C (Found: C, 72.3; H, 10.8. C19H32O3.0.5H2) requires C, 71.9; 10.5%), vmax/cmµ1 3501, 3405, 3310; dH (CDCl3) 0.74 (3 H, s, 18-H), 1.00 (3 H, s, 19-H), 3.64 (1 H, t, J 8.4 Hz, 17a-H), 4.10 (1 H, tt, J 4.5 and 11 Hz, 2b-H).Finally elution with 35% ethyl acetate:light petroleum gave 3b,5a,17b-trihydroxy-androstane (386 mg), plates, mp 193–195 °C (lit.,13 194–105 °C). S. N. thanks the Eastern University, Sri Lanka, for study leave and the British Council for financial assistance. Received, 24th March 1997; Accepted, 22nd April 1997 Paper E/7/02014G References 1 H. C. Brown and K. A. Keblys, J. Am. Chem. Soc., 1964, 86, 1791. 2 H. C. Brown and O. J. Cope, J. Am. Chem. Soc., 1964, 86, 1801. 3 H. C. Brown and R. M. Gallivan, J. Am. Chem. Soc., 1968, 90, 2906. 4 E. Dunkelblum, R. Levene and J. Klein, Tetrahedron, 1972, 28, 1009. 5 J. R. Hanson, P. B. Hitchcock, M. Liman and S. Nagaratnam, J. Chem. Soc., Perkin Trans. 1, 1995, 2183. 6 M. Alam, J. R. Hanson, M. Liman and S. Nagaratnam, J. Chem. Res. (S), 1997, 56. 7 G. C. Wolf and R. T. Blikenstaff, J. Org. Chem., 1976, 41, 1254. 8 P. S. Wharton and D. H. Bohlen, J. Org. Chem., 1961, 26, 3616. 9 H. L. Holland, J. A. Roas and P. C. Chenchaiah, J. Chem. Soc., Perkin Trans. 1, 1988, 2027. 10 J. E. Bridgeman, P. C. Cherry, A. S. Clegg, J. M. Evans, Sir Ewart Jones, A. Kasal, V. Kumar, G. D. Meakins, Y. Morisawa, E. E. Richards and P. D. Woodgate, J. Chem. Soc. (C), 1970, 250. 11 Dictionary of Steroids, ed. R. A. Hill, D. N. Kirk, H. L. Makin and G. M. Murphy, Chapman and Hall, London, 1992. 12 K. I. H. Williams, Steroids, 1963, 1, 377. 13 S. Julia, P. A. Plattner and H. Heusser, Helv. Chim. Acta, 1952, 35, 665.

ISSN:0308-2342    

DOI:10.1039/a702014g

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Me NAr NHAr + CN CN O O O O CN NAr Me NAr NH 1a–d 2 3a–d NAr NAr OH O CN NH NAr NHAr O– O CN NH O O CN 4a–d NAr NH NHAr + 5a–d O O CN CN 7 6a–d a Ar = Ph b Ar = 4-MeC6H4 c Ar = 4-MeOC6H4 d Ar = 4-ClC6H4 284 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 284–285† Reaction of N1,N2-Diarylacetamidines with 2,3-Dicyano- 1,4-naphthoquinone† Mohsen A. Gomaa,* Shaaban K. Mohamed and Ahmed M. Nour El-Din Chemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Arab Republic of Egypt The reaction of the N1,N2-diarylacetamidines 1a–d with 2,3-dicyano-1,4-naphthoquinone (2) led to the formation of benzo[f ]isoquinoline derivatives 6a–d; the reaction mechanism is discussed. One of the two cyano groups of 2,3-dicyano-1,4-naphthoquinone 2 undergoes substitution with primary amines, while the second cyano group is inert towards nucleophilic substitution. 1 Arylaminopyrazoles react with the nitrile 2 by replacement of one of the cyano groups followed by the addition (by their amino group) on the second cyano group to give pyrazolo[2,3-a]quinazolinediones.2 From the reaction of 2 with N,N-diarylbenzylideneanilines, 2-arylamino-3-cyano- 1,4-naphthoquinone together with the corresponding aldehydes are obtained, probably due to the hydrolysis of the primary substitution products.3 In an earlier publication4 we reported that the reaction of 2-(1,3-dioxo-2,3-dihydro-1Hinden- 2-ylidene)malononitrile 7 with N,Np-diarylacetamidines affords the corresponding indeno[1,2-d]azepines.However it has been reported that 7 undergoes a fast rearrangement with electron donors like acetamidines into 2,3-dicyano-1,4-naphthoquinone (2).5 Here we present the results obtained with the reaction of the diarylacetamidines 1a–d with 2. These results are compared with those obtained with the isomer of 2, i.e. 7. N1,N2-Diarylacetamidines 1a–c reacted with 2 in ethyl acetate at room temperature to give the benzo[ f ]isoquinolines 6a–d (in 40–72% yield).The IR spectra of 6a–d showed characteristic absorptions at vmax 3307–3340 cmµ1 for the hydroxy groups and at 3240–3250 cmµ1 for the NH group with further bands at 2190–2195 cmµ1 for the CN group and at 1681–1682 cmµ1 for the CO group. 1H NMR AB patterns with dA 2.99–3.02 and dB at 3.31–3.36 with |2J|-values 17.02–17.31 Hz are assigned to the C-1 methylene group adjacent to the chiral carbon atom C-10b. The presence of this methylene group is also evident from the 13C-DEPT spectra which exhibit negative signals at d 38.63–38.87. The broad band 1H-decoupled 13C NMR spectra showed one signal each at d 79.30–82.5 for C-10b bearing the hydroxy group and one signal each at d 117.71–119.50 for the cyano group.It is interesting to mention that the position of the signals of the olefinic C-atoms bearing the cyano groups, i.e. C-5 in 6a–d, show up at relatively higher field at d 57.06–57.20. The unexpected upfield shift in the range d 57–60 for the sp2 carbon attached to the nitrile group has been previously reported.6,7 It is plausible that the origin of the methylene group is the acetyl-derived methyl group in the acetamidines 1a–d.The formation of the benzo [ f ]isoquinolines 6a–d can be rationalized as follows: initial nucleophilic attack by the N2 of 1a–d on one nitrile carbon of 2 gives rise to compounds 3a–d which are in equilibrium with the tautomers 4a–d.8,9 The latter, being essentially ketene aminals, exhibit nucleophilic character at the terminal methylene carbon atom which attacks C-1 of 2 giving 5a–d which are ultimately isolated as 6a–d.From the above findings it may be concluded that the reaction of 7 with the acetamidines 1a–d is faster than the isomerization to 2. This may be ascribed to the fact that the basicity of the acetamidines 1a–d is not big enough to catalyse such a rearrangement. Experimental Melting points are uncorrected and obtained using a Griffin Georg melting point apparatus. Elemental analyses were obtained using a Carlo Erba 1106 CHN-analyser. Ir spectra were run as potassium bromide discs using a Shimadzu 470 spectrometer. 1H and 13C NMR were run at 300 and 75 MHz respectively using a Bruker WM 300 spectrometer with TMS as internal standard, m=multiplet.Mass spectra were run at 70 eV electron impact mode using a MAT 311A in connection with an AMD DP-10 data processing system. For preparative layer chromatography (PLC), an air dried 1.0 mm thick layer of slurry applied silica gel Merck PF254 on 48 cm wide and 20 cm high glass plates was employed using the solvents listed.Zones were detected by quenching of indicator fluorescence upon exposure to 254 nm light and eluted with acetone or ethyl acetate. The starting materials 2,3-dicyano-1,4-naphthoquinone10 (2) and N,Np-diarylacetamidines11 1a–d were prepared according to literature procedures. General Procedure for the Reaction of N,Np-Diarylacetamidines 1a–d with 2,3-Dicyano-1,4-naphthoquinone (2).·A solution of 2 (208 mg, 1.0 mmol) in 10 ml ethyl acetate was added dropwise to a solution of acetamidine (1a–d, 1.0 mmol) in 10 ml ethyl acetate at room temperature. After 10 min yellow crystals of benzo[ f ]isoquinolines 6a–d precipitated which were filtered off and recrystallized from ethyl acetate.The filtrate was evaporated and the residue was subjected to PLC using toluene–ethyl acetate (2:1) as eluent to give one zone which contained compounds 6a–d.*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 285 1 0 b - H y d r o x y - 4 - i m i n o - 3 - p h e n y l - 2 - p h e n y l i m i n o - 6 - o x o- 1 , 2 , 3 , 4 , 6 , 1 0 b - hexahydrobenzo[f]isoquinoline-5-carbonitrile (6a).·Yellow crystals (300 mg, 72%) mp 210–211 °C (from ethyl acetate), vmax (KBr)/ cmµ1 3321 (OH), 3240 (NH), 2184 (CN), 1682 (CO); dH (300 MHz, [2H6]DMSO) 2.99 (1 H, d, 1ap-H), 3.35 (1 H, d, 1bp-H, |2J| 17.15 Hz, CH2), 6.87, 7.02, 7.30, 7.39, 7.81, 7.83 and 7.97 (14 H, all m, aryl-H) and 7.50 (2 H, br, NH and OH); dC (75 MHz, [2H6]DMSO) 38.87 (C-1), 57.09 (C-5), 82.50 (C-10b), 118.50 (CN), 120.81, 120.59, 125.26, 127.18, 128.32, 128.98, 129.76 and 135.39 (all aryl- CH), 131.24 and 134.06 (C-6a and C-10a), 135.75 (C-4a), 148.61 (two aryl-C-N), 158.34 (C-2), 163.50 (C-4) and 193 (C-6); m/z 418 (M+, 6%), 391 (15), 247 (75), 210 (28), 170 (16), 155 (31), 118 (100), 93 (50), 77 (97) (Found: C, 74.52; H, 4.41; H, 13.20.C26H18N4O2 requires C, 74.62; H, 4.34; N, 13.39%). 1 0 b - Hydroxy- 4 - imino- 3 - (4 - methylphenyl) - 2 - (4 - methylphenylimino) - 6 - oxo- 1,2,3,4,6,10b - hexahydrobenzo[f]isoquinoline- 5 - carbonitrile (6b).·Yellow crystals (178 mg, 40%) mp 172–173 °C (from ethyl acetate); vmax (KBr)/cmµ1 3314 (OH), 3240 (NH), 2192 (CN), 1682 (CO); dH (300 MHz, [2H6]DMSO) 2.23 (3 H, s, CH3), 2.39 (3 H, s, CH3), 2.99 (1 H, d, 1ap-H), 3.33 (1 H, d, 1bp-H |2J| 17.31 Hz, CH2), 4.03 (2 H, br, NH and OH) and 6.75, 7.09, 7.25, 7.38, 7.63, 7.82 and 7.94 (12 H, all m, aryl-H); dC (75 MHz, [2H6]DMSO) 20.54 and 20.96 (two CH3), 38.86 (C-1), 57.20 (C-5), 80.50 (C-10b), 119.50 (CN), 122.73, 127.07, 128.05, 129.71, 130.40 and 135.59 (all aryl-CH), 125.31 and 131.19 (C-6a and C-10a), 132.59 (C-4a), 138.79 (two aryl-C-CH3), 145.88 (two aryl-C-N), 158.27 (C-2), 163.50 (C-4) and 193.01 (C-6); m/z 466 (M+, 4%), 419 (34), 404 (10), 390 (4), 329 (17), 278 (15), 261 (15), 171 (10), 106 (100), 91 (22), 77 (19) (Found: C, 75.45; H, 5.12; N, 12.32.C28H22N4O2 requires C, 75.32; H, 4.97; N, 12.55%). 10b - Hydroxy- 4 - imino- 3 - (4 - methoxyphenyl) - 2 - (4 - methoxyphenylimino- 6 - oxo- 1,2,3,4,6,10b - hexahydrobenzo[f]isoquinoline- 5 - carbonitrile (6c).·Yellow crystals (200 mg, 42%) mp 159 °C (from ethyl acetate); vmax (KBr)/cmµ1 3340 (OH), 3240 (NH), 2187 (CN), 1682 (CO); dH (300 MHz, [2H6]DMSO) 3.02 (1 H, d, 1ap-H), 3.36 (1 H, d, 1bp-H, |2J| 17.23 Hz, CH2), 3.69 (3 H, s, OCH3), 3.82 (3 H, s, OCH3), 6.84, 7.13, 7.36, 7.63, 7.82 and 7.95 (12 H, all m, aryl-H) and 6.88 (2 H, br, NH and OH); dC (75 MHz, [2H6]DMSO) 38.63 (C-1), 55.08 and 55.39 (two OCH3), 57.06 (C-5), 79.30 (C-10b), 114.24, 114.98, 121.78, 125.10, 126.71, 129.25, 130.53 and 135.31 (all aryl-CH), 119.5 (CN), 125.78 and 127.28 (C-10a and C-6a), 136.80 (C-4a), 140.97 (two aryl-CN), 155.70 and 159.50 (two aryl- C-OCH3), 159.50 (C-2), 163.90 (C-4) and 193.08 (C-6); m/z 478 (M+, 5), 451 (26), 436 (34), 420 (5), 419 (13), 345 (13), 294 (81), 149 (7), 123 (83), 108 (100), 92 (5), 77 (11) and 65 (6) (Found: C, 69.98; H, 4.70; N, 11.60.C28H22N4O4 requires C, 70.28; H, 4.62; N, 11.71%). 10b - Hydroxy - 4 - imino - 3 - (4 - chlorophenyl) - 2 - (4 - chlorophenylimino) - 6 - oxo- 1,2,3,4,6,10b- hexahydrobenzo[f]isoquinoline- 5 - carbonitrile (6d).·Yellow crystals (314 mg, 65%) mp 175–178 °C (from ethyl acetate); vmax (KBr)/cmµ1 3307 (OH), 3250 (NH), 2192 (CN), 1681 (CO); dH (300 MHz, [2H6]DMSO) 3.01 (1 H, d, 1ap-H), 3.31 (1 H, d, 1bp-H, |2J| 17.02 Hz, CH2), 6.92, 7.32, 7.40, 7.61, 7.86 and 7.98 (12 H, all m, aryl-H), and 7.67 (2 H, br, NH and OH); dC (75 MHz, [2H6]DMSO) 38.86 (C-1), 57.15 (C-5), 84 (C-10b), 118.55 (CN), 122.51 (C-10a), 122.83, 125.24, 127.29, 129.09, 129.62, 130.24, 132 and 135.65 (all aryl-CH), 127.63 (C-6a), 133.13 and 133.34 (aryl-C-Cl), 135.65 (C-4a), 147.68 (two aryl-C-N), 158.93 (C-2), 162.50 (C-4) and 192.84 (C-6); m/z 487 (M+, 18), 348 (7), 298 (14), 152 (23), 127 (100), 92 (18), 76 (10) and 65 (22) (Found: C, 64.12; H, 3.20; N, 11.42.C26H16Cl2N4O2 requires C, 64.06; H, 3.31; N, 11.50%). We are indebted to Prof. Dr Dietrich D�opp, Division of Organic Chemistry, Gerhard Mercator Universit�at GH Duisburg, for measuring the elemental analyses, 1H NMR and mass spectra. Received, 3rd February 1997; Accepted, 18th April 1997 Paper E/7/00766C References 1 K.-Z. Chu and J. Griffins, J. Chem. Soc., Perkin Trans. 1, 1978, 1083. 2 A. A. Hassan, N. K. Mohamed, Y. R. Ibrahim and A. E. Mourad, Liebigs Ann. Chem., 1993, 695. 3 M. A. Gomaa, Bull. Chem. Soc. Jpn., 1995, 68, 3131. 4 D. D�opp, M. A. Gomaa, G. Henkel and A. M. Nour El-Din, J. Chem. Soc., Perkin Trans. 2, 1996, 573. 5 G. J. Ashwell, M. R. Bryce, S. R. Davies and M. Hassan, J. Org. Chem., 1988, 53, 4585. 6 R. Dworczk, H. Sterk, C. Kratky and H. Junek, Chem. Ber., 1989, 122, 1323. 7 W. Bremser, B. Frank and H. Wagner, Chemical Shift Ranges in NMR Spectroscopy, Verlag Chemie, Weinheim, 1982. 8 H. P. Figeys, A. Mathy and A. Dralants, Synth. Commun., 1981, 11, 655. 9 M. Pfau, M. Chiriacescu and G. Revial, Tetrahedron Lett., 1993, 34, 327. 10 G. A. Renolds and J. A. Vanallan, J. Org. Chem., 1964, 29, 3591. 11 E. C. Taylor and W. A. Erhart, J. Org. Chem., 1963, 28,

ISSN:0308-2342    

DOI:10.1039/a700766c

出版商:RSC    

年代:1997

数据来源: RSC