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11. |
Kinetics of the Reactions of O·-andHO· with α,α,α-Trifluorotoluene and4-Fluorotoluene† |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 172-173
Laura S. Villata,
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摘要:
172 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 172–173† Kinetics of the Reactions of O.µ and HO. with a,a,a-Trifluorotoluene and 4-Fluorotoluene† Laura S. Villata, Janina A. Rosso, M�onica C. Gonzalez* and Daniel O. M�artire*‡ Instituto de Investigaciones Fisicoqu�ýmicas Te�oricas y Aplicadas (INIFTA), Casilla de Correo 16, sucursal 4, (1900) La Plata, Argentina The absolute rate constants for the reactions of O.µ and HO. with a,a,a-trifluorotoluene and 4-fluorotoluene were obtained by flash photolysis.The photolysis of strong alkaline solutions (pHa12.7) of hydrogen peroxide (pKa=11.61) yields HO./O.µ radicals (pKa211.9) [eqns. (1) and (µ1) in Table 1]. In the presence of molecular oxygen, O.µ radicals reversibly react with O2 yielding ozonide radical ions, O3 .µ [eqns. (2) and (3)] .2–4 Ozonide itself is thought to be rather unreactive towards non-radical substrates; however its decay rate is extremely sensitive to small quantities of HO./O.µ scavengers.5–7 In previous investigations4 it has been shown that in solutions containing H2O2 concentrations of the order of 5Å10µ5 mol dmµ3 or larger and added substrates (S), competition between H2O2, S and O2 for O.µ/HO.radicals rules the formation efficiency and decay rate of O3 .µ. A detailed kinetic study on the O3 .µ concentration profiles following flash photolysis of alkaline hydrogen peroxide solutions in the presence of scavengers yields kinetic information on the reactions between O.µ/HO. and the substrates [eqns.(6) and (7)].4 Based on this methodology, we report here a kinetic study of the reactions of O.µ/HO. radicals with a,a,a-tri- fluorotoluene (TFT) and 4-fluorotoluene (4-FT). Experimental Hydrogen peroxide (Riedel-de Ha�en), TFT and 4-FT (Fluka) were used as received. The flash-photolysis set-up and experimental procedures are described elsewhere.4 All the experiments were carried out at 25�1 °C. In order to study the effect of substrates on the O3 .µ decay kinetics, a series of experiments with 1.16Å10µ4 mol dmµ3 hydrogen peroxide and systematic variations in the amounts of substrate (0–4Å10µ3 mol dmµ3) and pH were performed.Results and Discussion The time-resolved absorption curves obtained in the range 350–700 nm show the presence of a single intermediate identified as O3 .µ by its characteristic absorption spectrum.4 The traces can be well described by a first-order law over more than three lifetimes under all the experimental conditions (Fig. 1). The observed rate constant, kapp, linearly depends on the analytical concentration of added substrate at constant pH as shown in Fig. 2 (inset). Previous investigations on the photolysis of alkaline solutions of hydrogen peroxide, have shown that reactions (1)–(5) in Table 1 are the main reactions leading to ozonide formation and decay.4 If organic substrates such as 4-FT and TFT are added, they will also contribute to the depletion of O.µ/HO.according to reactions (6) and (7). Any possible reaction of O.µ/HO. and O3 .µ with the radical products, S., formed from eqns. (6) and (7) should also be considered. The total amount of S. formed can be estimated from the ratio of the areas of the ozonide decay profiles in the presence and absence of scavenger, respectively. For experiments with the highest concentrations of scavenger, [S.]total ss8Å10µ7 mol dmµ3. Consequently, S. cannot compete for O.µ/HO.radicals with the efficient scavenging by much larger concentrations of H2O2 and substrates, and eqn. (8) is negligible under our experimental conditions. However, the contribution of the reaction of S. with O3 .µ [eqn. (9)] cannot be evaluated a priori without a complete kinetic analysis. In a simplified analysis, reaction (9) will not be considered. O.µ/HO.+S.hProducts (8) O3 .µ+S.hProducts (9) The reaction mechanism shown in Table 1 can be analytically resolved assuming steady-state conditions for the extremely reactive O.µ and HO.radicals. From this kinetic analysis, a first-order law is expected for the decay of ozonide radical ions.4 The first-order apparent rate constant kapp is given by eqn. (10). A more detailed discussion on the reaction mechanism and kinetic analysis can be found in the literature.4 kapp= k3{kp[HOµ2 ]+ks[S]} k2[O2]+kp[HOµ2 ]+ks[S] (10) *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). ‡E-mail: dmartire@volta.ing.unlp.edu.ar. Table 1 Manifold of important reactions leading to the formation and decay of ozonide radical ions in the presence of efficient O.µ/HO. radical scavengersa Reaction k/dm3 molµ1 sµ1 HO.+HOµhO.µ O.µ+H2OhHO.+HOµ O.µ+O2hO3 .µ O3 .µhO.µ+O2 HO.+HOµ2 hO2 .µ+H2O O.µ+HOµ2 hO2 .µ+HOµ O.µ+ShProducts OH.+ShProducts 1.3Å1010 1.8Å106 3.6Å109 3.6–6.0Å103 sµ1 b 9.0Å109 5.0Å108 (1) (µ1) (2) (3) (4) (5) (6) (7) aTaken from refs. 5, 9 and 11. bThe value 4.0Å103 sµ1 was used at 25 °C, in line with the reported value for the activation energy of this reaction (46 kJ molµ1).12 Fig. 1 Logarithmic plots for the decay of [O3 .µ] obtained for airsaturated alkaline 1.16Å10µ4 mol dmµ3 H2O2 solutions (pH=13.9) containing (a) no added scavengers, (b) 3.87Å10µ5 mol dmµ3 4-FT and (c) 1.61Å10µ3 mol dmµ3 TFT: solid lines represent computer simulations of the decays (see text)J.CHEM. RESEARCH (S), 1997 173 with ks=k6+k7Kµ1[H+] kp=k5+k4[H+] /K K=[O.µ][H+]/[HO.] =1.26Å10µ12 (11) If k2[O2]+kp[HO2 µ]aaks[S], then the linear dependence of kapp on [S] is expected as observed experimentally. The ratio of the slope (b) to the intercept (a) of the plots of kapp vs. [S] (Fig. 2), times [HOµ2 ]Åkp yields ks at a given pH. According to eqn. (11), ks should linearly depend on [H+] as experimentally observed (Fig. 2). A least-squares analysis of the plots shown in Fig. 2 allows determination of k6 and k7 for each substrate from the intercept and slope, respectively. The values k6=(4�2)Å108 dmµ3 molµ1 sµ1, k7=(6�1)Å109 dm3 molµ1 sµ1 and k6=(2�1)Å107 dm3 molµ1 sµ1, k7=(1.1�0.2)Å109 dm3 molµ1 sµ1 are retrieved for 4-FT and TFT, respectively. The errors in the rate constants were estimated from the dispersions observed for the intercepts and the slopes in Fig. 2. In order to support the simplified kinetic analysis, other literature reactions involving the species present in the irradiated system,4 and not shown in Table 1, were considered in a kinetic simulation program together with reactions (6) and (7). An excellent agreement between experimental and simulated data was obtained for the observed kinetics of O3 .µ, also shown in Fig. 1, using the values of k6 and k7 retrieved from the simplified analysis. Thus, the contribution of reactions other than those shown in Table 1 is negligible under our experimental conditions.Reaction (9) between O3 .µ and the S. radicals was not considered in a first approximation, though its participation in the overall mechanism is expected to accelerate the decay kinetics of ozonide radical ions. Consequently, the retrieved values of k6 and k7 are upper limits for these rate constants. The contribution of this reaction to the concentration pro- files of O3 .µ in the presence of added S was evaluated with the aid of the computer simulation program.The simulations show that taking k9=2Å1010 dm3 molµ1 sµ1, and in the extreme conditions where no other decay reaction for S. is considered, the values of k6 and k7 that best fozonide profiles are 50% lower than those estimated without considering eqn. (9). There is almost no contribution from this reaction to the ozonide decay if k9R5Å108 dm3 molµ1 sµ1. The reactions of substituted benzenes with O.µ/HO.are known to yield reactive hydroxycyclohexadienyl and/or benzyl radicals.8 Consequently, S. may undergo other reactions in competition with reaction (9), and the effect of the latter reaction on the estimated values of k6 and k7 will be much lower than 50%. Thus, any possible effect of reaction (9) is already included within the reported error bars for k6 and k7, even in the case that eqn. (9) is diffusion-controlled. The rate constant obtained for the reaction of HO.and TFT is lower than the reported ones for toluene [(3–7)Å109 dm3 molµ1 sµ1] and benzene (5.0Å109 dm3 molµ1 sµ1), and similar to that for nitrobenzene (2Å109 dm3 molµ1 sµ1).9 This trend is expected from a radical addition of HO. to the aromatic ring, considering the electron-withdrawing ability of the CF3 group. On the other hand, the rate constant for the reaction of 4FT and HO. is of the same order as the reported values for other toluenes with para electron-withdrawing substituents (i.e. 7Å109, 2.9Å109 and 5.5Å109 dm3 molµ1 sµ1 for p-nitrotoluene, p-bromotoluene and p-chlorotoluene, respectively).9,10 The rate constant obtained for the reaction of O.µ and TFT is two orders of magnitude smaller than that observed for toluene (2.1Å109 dm3 molµ1 sµ1), but of the same order of magnitude than the reported ones for benzene (7.5Å107 dm3 molµ1 sµ1), benzonitrile (7Å107 dm3 molµ1 sµ1) and nitrobenzene (5Å107 dm3 molµ1 sµ1). The higher reactivity of O.µ with toluene indicates the preferential reaction of this radical by H abstraction from aliphatic side chains of the aromatic molecules, rather than by addition to the aromatic ring.9 On the other hand, the rate constant obtained for the reaction of O.µ and 4-FT is of the same order as the reproted values for other toluenes containing electron-withdrawing substituents, such as nitrotoluene (7.6Å108 dm3 molµ1 sµ1).9 M.C. G. and D. O. M. are research members of CONICET and CICPBA, respectively. This research was partially supported by grants number A-13218/1-000062 and A-13359/1-000084 of Fundaci�on Antorchas (Argentina) Received, 6th January 1997; Accepted, 4th February 1997 Paper E/7/00126F References 1 K.Chelkowska, D. Grasso, I. F�abi�an and G. Gordon, Ozone Sci. Eng., 1992, 14, 33. 2 J. Hunt and H. Taube, J. Am. Chem. Soc., 1952, 74, 5999. 3 J. H. Baxendale and J. A. Wilson, Trans. Faraday Soc., 1957, 53, 344. 4 M. C. Gonzalez and D.O. M�artire, Int. J. Chem. Kin., in press. 5 K. Sehested, J. Holcman, E. Bjerbakke and E. J. Hart, J. Phys. Chem., 1982, 86, 2066. 6 B. L. Gall and L. M. Dorfman, J. Am. Chem. Soc., 1969, 91, 2199. 7 G. Czapski, Annu. Rev. Phys. Chem., 1971, 22, 171. 8 (a) C. von Sonntag and H.-P. Schuchmann, Angew. Chem., Int. Ed. Engl., 1991, 30, 1229; (b) P. Neta, J. Grodkowski and A. B. Ross, J. Phys. Chem. Ref. Data, 1996, 25, 709. 9 (a) G. V. Buxton, C. L. Greenstock, W. P. Helman and A. B. Ross, J. Phys. Chem. Ref. Data, 1988, 17, 513; (b) Farhataziz and A. B. Ross, Selected Specific Rates of Reactions of Transients from Water in Aqueous Solutions. II. Hydroxyl Radical and Perhydroxyl Radical and Their Radical Ions, NSRDS-NBS 59, National Bureau of Standards, Washington DC, 1977. 10 G. Merga, B. S. M. Rao, H. Mohan and J. P. Mittal, J. Phys. Chem., 1994, 98, 9158. 11 P. Neta, R. E. Huie and A. B. Ross, J. Phys. Chem. Ref. Data, 1988, 17, 1027. 12 D. Behar, J. Phys. Chem., 1974, 78, 2660. Fig. 2 Plots of (b/a)Å[HO– 2]kp vs. [H+] for (d) TFT and (s) 4-FT: the error in each data point was estimated from the dispersion in the calculated values of a and b. For 4-FT, the error bars are of the same size as the symbols. Inset: Plots of kapp vs. [S] for air-saturated alkaline solutions containing 1.16Å10µ4 mol dmµ3 H2O2 and (a) TFT, pH=12.9; (b) TFT, pH=13.3; (c) 4-FT, pH=12.9 (upper
ISSN:0308-2342
DOI:10.1039/a700126f
出版商:RSC
年代:1997
数据来源: RSC
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12. |
Montmorillonite Clay Catalysis. Part 4.1An Efficient and Convenient Procedure for Preparation of1,1-Diacetates from Aldehydes |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 174-175
Zhan-Hui Zhang,
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摘要:
RCHO RCH(OAc)2 K-10 or KSF Ac2O, room temperature, 0.2–6 h 1 2 0–98% 174 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 174–175† Montmorillonite Clay Catalysis. Part 4.1 An Efficient and Convenient Procedure for Preparation of 1,1-Diacetates from Aldehydes† Zhan-Hui Zhang, Tong-Shuang Li* and Cheng-Guang Fu Department of Chemistry, Hebei University, Baoding 071002, Hebei Province, P.R. China An easy preparation of 1,1-diacetates from aldehydes with montmorillonite clays as catalysts has been carried out in excellent yield. 1,1-Diacetates have attracted considerable attention owing to their moderate stability and easy conversion into parent aldehydes. 2–7 They are an alternative protecting group to acetals for protecting aldehydes and can be used as starting materials for the synthesis of valuable intermediates for Diels–Alder cycloaddition reactions.8 Usually, the syntheses of 1,1-diacetates are carried out under the catalysis of strong proton acids, such as sulfuric acid,9,10 phosphoric or methanesulfonic acid,10 and Lewis acids, such as zinc chloride.11 These methods have not been entirely satisfactory, owing to such drawbacks as low yields, long reaction times, corrosivity, difficult work-up and effluent pollution. In recent years, several catalysts have been employed for this reaction to improve yields, to decrease reaction time and to eliminate the mentioned unfavourable effects.Phosphorus trichloride was used as a catalyst resulting in good yields with most aldehydes, but the yields were poor for aromatic aldehydes containing electron- withdrawing groups.12 Kochlar et al.2 developed a fast reaction (less than 30 min), catalysed by iron(III) chloride, even for a,b-unsaturated aldehydes and aromatic aldehydes having electron-withdrawing groups.Nafion-H,13 Y-zeolite,14 b-zeolite,15 sulfated zirconia16 and HZSM-517 have been relatively successfully used as catalysts for the conversion of aldehydes into 1,1-diacetates.Montmorillonite clays have been used as efficient catalysts for a number of organic reactions and offer several advantages over classic acids: strong acidity, non-corrosivity, cheapness, mild reaction conditions, high yield and selectivity, and ease of set-up and work-up.18 Here we report an easy and efficient procedure for the synthesis of 1,1-diacetates from aldehydes catalysed by montmorillonite clays (Scheme 1). As shown in Table 1, a series of 1,1-diacetates 2 were synthesized using montmorillonite K-10 or KSF as a catalyst at room temperature.K-10 and KSF gave similar results in terms of reaction time and yield. Both aromatic and aliphatic aldehydes gave high, although unmaximized, yields of the corresponding 1,1-diacetates. For example, furfural gave 2-furylmethanediyl diacetate (2j) in 74% yield and chloral diacetate (2b) was obtained in 53% yield after distillation. 4-Nitrobenzaldehyde (1h) required a relatively longer reaction time (6 h), possibly owing to the strong electron-withdrawing nitro substituent.Interestingly, the a,b-unsaturated aldehyde 1k gave a better yield in a shorter reaction time than the previously mentioned methods.2,12,16 *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 Table 1 Conversion of aldehydes into 1,1-diacetates in the presence of montmorillonite clays Mp (T/°C) [bp (T/°C)/Torr] Aldehyde 1 Diacetate 2 Catalyst/Solvent R R Time (t/h) Yield (%) Found Reported Et (1a) Cl3CCH(OH)2 (1b) Ph (1c) 4-MeC6H4 (1d) 4-MeOC6H4 (1e) 4-ClC6H4 (1f) 3-ClC6H4 (1g) 4-O2NC6H4 (1h) 3-O2NC6H4 (1i) 2-furyl (1j) PhCH�CH (1k) 2-HOC6H4 (1l) 3-MeO-4-HOC6H3 (1m) 3,4-(OCH2O)C6H3 (1n) 4-HOC6H4 (1o) 4-Me2NC6H4 (1p) Me2N (1q) Et (2a) Cl3C (2b) Ph (2c) 4-MeC6H4 (2d) 4-MeOCH6H4 (2e) 4-ClC6H4 (2f) 3-ClC6H4 (2g) 4-O2NC6H4 (2h) 3-O2NC6H4 (2i) 2-furyl (2j) PhCH�CH (2k) 2-AcOC6H4 (2l) 3-MeO-4-AcOC6H3 (2m) 3,4-(OCH2O)C6H3 (2n) no reaction no reaction no reaction K-10/none/0.8 K-10/none/4 K-10/none/0.2 KSF/none/0.2 K-10/none/0.5 K-10/none/0.5 K-10/CCl4/1 KSF/CCl4/0.6 K-10/none/1 KSF/none 0.6 K-10/CCl4/6 KSF/CCl4/6 K-10/none/4 KSF/none/4 K-10/none/2 K-10/none/0.5 K-10/none/1 K-10/none/1 K-10/none/0.5 KSF/none/0.5 K-10/none/48 KSF/none/48 K-10/none/48 KSF/none/48 K-10/none/48 KSF/none/48 87 53 98 98 98 98b 96 95 94b 96 90 96 94 94 74 97b 93b 92b 98b 96 —c —c —c —c —c —c [105–109/35] [145–148/32] 44–45 80.5–81.5 64–65 81–82 65–66 125.5–126.5 64–66 50.5–51.5 83.5–84.5 103–104 90–91 78–79 115–118/82 98–99/619 44–454 81–824 64–654 80–814 65–6610 123–12512 64–662 50–5110 84–8712 104–10520 79–8010 75–7610 aIsolated yield.bSatisfactory elemental analysis obtained: C�0.20, H�0.19%. c100% aldehyde was recovered.J. CHEM. RESEARCH (S), 1997 175 It is worth noting that the hydroxy groups in 2-hydroxyand 3-methoxy-4-hydroxy-benzaldehyde (1l and 1m) were also acetylised to afford the corresponding triacetates 2l and 2m under these conditions.The scope and limitation of this method were investigated. N,N-Dimethylformamide (1q) was not acetylised with acetic anhydride even under reflux for 3 h in the presence of K-10 or KSF. Ketones, such as cyclohexanone and acetophenone, were not converted into the corresponding 1,1-diacetates at room temperature.Therefore the present procedure is a selective preparation of the 1,1-diacetates 2 of aldehydes in the presence of ketones. We also attempted the reaction of maleic anhydride, phthalic anhydride and succinic anhydride with benzaldehyde (1c) with K-10 or KSF as catalyst. However, none of these reagents gave the expected cyclic diesters even when the reaction mixtures were stirred either at room temperature for 2 d or under reflux for 2 h.The starting materials were quantitatively recovered. It is worth noting that when 4-hydroxybenzaldehyde (1o) and 4-(dimethylamino) benzaldehyde (1p) were treated with acetic anhydride with K-10 or KSF as catalyst, to our surprise, none of the reactions gave the corresponding products even when the reaction mixtures were stirred at room temperature for 2 d. The starting materials were quantitatively recovered. We propose, as an explanation for this result, that selective adsorption of the phenolic and amino compounds (1o and 1p) at the hydroxy and dimethylamino groups of the catalyst occurs.This might keep the aldehyde away from the active site thus stopping the reaction and blocking the sites. Compound 1l would adsorb favourably for the reaction. The hydrogen bond and the bulk of the methoxy group in 1m might be enough to discourage adsorption in the ‘wrong’ manner. In conclusion, we have provided an alternative preparation of 1,1-diacetates from aldehydes, with the advantages of selectivity, operational simplicity, high yields, short reaction times and minimal environmental impact.Experimental Boiling points and melting points are uncorrected. K-10 and KSF were purchased from Fluka and employed directly for the reactions. The products were characterized by their melting or boiling points and/or IR, 1H NMR and mass spectra. General Procedure for the Preparation of 1,1-Diacetates 2.·A mixture of the aldehyde 1 (10 mmol), acetic anhydride (30 mmol) and K-10 (or KSF) montmorillonite (200 mg) was stirred at room temperature for the time indicated in Table 1.For the reactions with solvent, CCl4 (5 mL) was also added. The reaction was monitored by TLC. Upon completion, Et2O (10 mL) was added to the reaction mixture and the catalyst was filtered off. The catalyst was washed with Et2O (2Å10 mL) and then the filtrate was washed with 10% HCl (20 mL) and brine (2Å20 mL) and then dried (MgSO4).The solvent was removed under reduced pressure and the residue was purified by distillation or crystallization from cyclohexane to give 1,1-diacetates 2 in 0–98% yields. This project was supp the National Natural Science Foundation of China, the Education Commission of Hebei Province and the Science and Technology Commission of Hebei Province. Received, 10th December 1996; Accepted, 10th February 1997 Paper E/6/08318H References 1 Part 3: T. S. Li and S. H. Li, Synth. Commun., 1997, in the press. 2 K. S. Kochhar, B. S. Bal, R. P. Deshpande, S. N. Rajadhyaksha and H. W. Pinnick, J. Org. Chem., 1983, 48, 1765. 3 J. Kula, Synth. Commun., 1986, 16, 833. 4 M. J. Gregory, J. Chem. Soc. B, 1970, 1201. 5 E. R. Perez, A. L. Marrero, R. Perez and M. A. Autie, Tetrahedron Lett., 1995, 36, 1779. 6 Y. Y. Ku, R. Patel and D. Sawick, Tetrahedron Lett., 1993, 34, 8037. 7 S. V. Lieberman and R. Connor, Org. Synth., 1951, Coll. Vol. II, 441. 8 B. B. Snider and S. G. Amin, Synth. Commun., 1978, 8, 117. 9 M. Tomita, T. Kikuchi, K. Bessho, T. Hori and Y. Inubushi, Chem. Pharm. Bull., 1963, 11, 1484. 10 F. Freeman and E. M. Karcherski, J. Chem. Eng. Data, 1977, 22, 355. 11 I. Scriabine, Bull. Soc. Chim. Fr., 1961, 1194. 12 J. K. Michie and J. A. Miller, Synthesis, 1981, 824. 13 G. A. Olah and A. K. Mehrotra, Synthesis, 1982, 962. 14 C. Pereira, B. Cigante, M. J. Marcelo-Curto, H. Carreyre, G. Perot and M. Guisnet, Synthesis, 1995, 1077. 15 P. Kumar, V. R. Hegda and T. P. Kumar, Tetrahedron Lett., 1995, 36, 601. 16 S. V. N. Raju, J. Chem. Res. (S), 1996, 68. 17 M. V. Joshi, C. S. Narasimhan and O. Mukesh, J. Catal., 1993, 141, 308. 18 For a recent review see: T. S. Li and T. S. Jin, Chin. J. Org. Chem., 1996, 16, 385. 19 N. S. Vulfson, Zh. Obshch. Khim., 1950, 20, 595 (Chem. Abstr., 1951, 45, 557b). 20 I. Hisashi and T. Seisuke, J. Pharm. Soc. Jpn., 1952, 72, 876 (Chem. Abstr., 1953, 47, 6413b).
ISSN:0308-2342
DOI:10.1039/a608318h
出版商:RSC
年代:1997
数据来源: RSC
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13. |
Tandem Conjugate Carbon Addition–IntermolecularHetero Diels–Alder Reactions using Ethyl1H-Perimidine-2-acetate as a Ketene Aminal with Heatingor Microwave Activation† |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 176-177
Françoise Cado,
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摘要:
N R 1 N 2 4 3 4 X EWG 3 1 2 1 2 R = R¢CO, PhSO2, Me2N, Ph EWG = CO2Et, CN X = O, S N N H CO2Et N N H H CO2Et H N N CO2Et H R R N N CO2Et H 1,5-prototropy R a R b 3 a b 3¢ 6 4 7 1 2 3 4 5 6 7 8 9 10 11 12 N N H 6a 7a CO2Et H 12a b a R 3a 5 1 2 3 4 5 R 4 6b 176 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 176–177† Tandem Conjugate Carbon Addition–Intermolecular Hetero Diels–Alder Reactions using Ethyl 1H-Perimidine-2-acetate as a Ketene Aminal with Heating or Microwave Activation† Françoise Cado,a Patrick Jacquault,b Marie-Jo�elle Dozias,b Jean Pierre Bazureau*a and Jack Hamelina aSynth`ese et Electrosynth`ese Organiques 3, CNRS-UMR 6510, Bat. 10, Universit�e de Rennes 1, Campus de Beaulieu, F-35042 Rennes C�edex, France bProlabo, 54 rue Roger Salengro, F-94126 Fontenay sous Bois, France The reaction of ethyl 1H-perimidine-2-acetate 3 as a heterocyclic ketene-aminal with 2.1 equiv. of ethyl propiolate 4a or but- 3-yn-2-one 4b affords new fused perimidines in good yields by a tandem C-addition/hetero Diels–Alder reaction; the new 1-azabuta-1,3-diene intermediates are generated in situ from the initial trans C-addition products by thermal 1,5-prototropy. The hetero Diels–Alder reaction involving heterodienophiles1 and/or heterodienes2 has become a powerful tool for the construction of heterocyclic rings, particularly in natural product synthesis.3 However, the Diels–Alder reactions of 1-azabuta- 1,3-dienes of simple a,b-unsaturated imines 1 suffer from low conversion, and/or imine tautomerization precluding [4+2] cycloaddition.2a To solve these problems, various 1-azabuta- 1,3-dienes carrying substituents at the 1-position (R=acyl,3 sulfonyl,4 dimethylamino,5 phenyl6) have been developed to avoid instability arising from the imine moiety.Recently, Sakamoto et al.7 reported an interesting type of 1-azabuta-1,3-diene 2 (Scheme 1) in which the imine moiety is stabilized when introduced in a heterocyclic ring, such as 1,3-benzoxazoles and 1,3-benzothiazoles.The dienes 2 react with both electron-deficient and electron-rich dienophiles in intermolecular [4+2] cycloadditions. A recurrent theme of our ongoing studies with ethyl 1H-perimidine-2-acetate 3 (Scheme 2) is the nucleophilic reactivity of the b-position. Perimidine 3 simultaneously exhibits the distinct properties of heteroatomic systems with an excess of and a deficiency of p-electrons.8 Owing to the conjugation effect of the electron-donating amino groups and electron-withdrawing substituents, the double bond Ca�Cb is highly polarized and the electron density on Cb is increased,9 leading to greater nucleophilicity of carbon when compared to nigrogen.10 Encouraged by using perimidine 3 as an N,C bisnucleophilic synthon towards annulation from a- and b-dielectrophiles,11 we report here the first results obtained for the synthesis of new fused perimidines by a tandem conjugate C-addition–hetero Diels–Alder reaction.Moreover, as part of our programme to develop organic syntheses under microwave irradiation,12 we extended these reactions using solvent-free conditions under focused microwaves.13a Results and Discussion Treatment of 3 with 1.1 equiv. of ethyl propiolate 4a (MeOH, reflux, 3 h) mainly afforded the insoluble trans C-addition product 5a14 (Scheme 2, Table 1). Further treatment of 3 with 2.1 equiv. of 4a in refluxing ethanol for 3 h led to the fused perimidine 7a in quantitative yield (Table 1).The assigned structures of 5a and 7a were substantiated by the 1H and 13C NMR and MS analyses. Starting from 5a and 4a (5a:4a=1:1) under the same reaction conditions (EtOH, reflux, 3 h), compound 7a was also obtained in 98% crude yield: we reasoned that, by reacting the initial C-addition product 5a with 4a, the tautomer 6a might be readily trapped by an aza-Diels–Alder cycloaddition with the dienophile 4a. Interestingly, when 5a was refluxed in EtOH for 3 h, the 1H NMR spectrum of the crude reaction mixture showed the presence of compounds 3 (50%) and 7a (50%) as a result of a retro-reaction to give 3 and 4a, the latter reacting with the remaining 5a to give 7a.Finally, when an equimolecular mixture of 5a and N-phenyl- or N-methyl-maleimide as dienophile were refluxed in ethanol for 12 h, no Diels–Alder reaction took place but the labile nature of the vinylene segment of Cb in 5a was observed by identification of compounds 7a *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 4a,5a,7a R=CO2Et 4b,5b,7b R=COMe Scheme 2 Table 1 Synthesis of perimidines 5a and 7a–b from 3 and 4a–b Product R Reaction conditions 4:3 Yield (%) 5a 7a 7b CO2Et CO2Et COMe MeOH, 65 °C, 3 h EtOH, 78 °C, 3 h EtOH, 78 °C, 5 h 1.1:1 2.1:1 2.1:1 67a 98 78b 98 50b aYield of crude 5a obtained after filtration on a Buchner funnel.bYield of crude product estimated by 1H NMR and after chromatography on silica gel.J. CHEM. RESEARCH (S), 1997 177 and 3 (7a:3=1:1): the formation of 7a can be explained via a retro-addition reaction from 5a in ethanol (Scheme 2). Mechanistically, the reaction proceeds via the initial formation of the trans compound 5a by regioselective Cb-addition of ethyl propiolate 4a to perimidine 3 which affords the 1-azabuta-1,3-diene 6a in situ, by thermal 1,5-prototropy, then 6a reacts with a second equivalent of 4a as dienophile and gives 7a by [4+2] cycloaddition.In a further demonstration of this methodology, treatment of 3 with but-3-yn-2-one 4b (EtOH, reflux, 5 h) afforded 7b together with a small amount of 5b (Scheme 2). Purification on silica gel (CH2Cl2–MeCN, 19:1 as eluent, Rf 0.36) gave pure 7b in 50% yield (Table 1). In order to shorten the synthetic route to 7a, solvent-free conditions in an oil bath or focused microwave irradiation were used.13a A Synthewave 402® microwave oven monitored by a computer which adjusts the temperature13b of the reaction mixture was used.Some typical examples are shown in Table 2. The main features of this technique are, complete addition in less than 8 minutes and ease of purification of 7a. When the same reaction mixture was heated in an oil bath previously set at the same boiling point for the same reaction time (entries 3,4 and 5,6) the results were analogous.In these cases, a specific microwave effect can be excluded as it is not expected in this polar solvent,15 but microwave heating affords a straightforward and efficient method for the preparation of 7a. Experimental General Procedure for the Preparation of Fused Perimidines 7.·A mixture of ethyl 1H-perimidine-2-acetate 3 (1 g, 3.9 mmol) and 4 (8.2 mmol) in dry ethanol (20 ml) was heated at 78 °C for 3 h under vigorous magnetic stirring.After elimination of ethanol in vacuo, the crude residue was purified by chromatography on silica gel. Solvent evaporation gave the desired compound 7 as a nearly pure oil which crystallized on standing. Diethyl 9-ethoxycarbonylmethyl-7,9-dihydropyrido[1,2-a]perimidine- 8,10-dicarboxylate 7a was prepared from ethyl propiolate 4a (0.8 g, 8.2 mmol) as a colourless powder, mp=144–146 °C (from CH2Cl2–MeCN, 19:1 as eluent, Rf 0.79), 78% yield; dH (CDCl3, 300 MHz) 1.00 (t, 3 H, J 7.1 Hz), 1.38 (t, 2Å3 H, J 7.1 Hz), 2.61 (d, 2 H, J 5.7 Hz), 3.55 (qd, 2 H, J 7.1 Hz), 4.25 (2Åq, 2Å2 H, J 7.1 Hz), 5.68 (t, 1 H, J 5.7 Hz), 6.52 (d, 1 H, H-4), 6.89 (d, 1 H, H-9), 7.21 (m, 4 H, Ar), 7.81 (s, 1 H, �CH), 12.21 (br s, 1 H, NH); dC (CDCl3, 75 MHz) 13.7 (qt, J 127, 2.7 Hz), 14.5 (qt, J 127, 2.5 Hz), 14.6 (qt, J 127, 2.5 Hz), 37.3 (td, J 132, 2.1 Hz), 50.5 (dt, J 147 Hz, CH), 60.0 (tq, J 147, 4.4 Hz), 60.2 (tq, J 147. 4.4 Hz), 60.9 (tq, J 147, 4.4 Hz), 81.8 (s, C-8), 105.5–106.1 (dd, J 161 Hz, C-1, C-6), 105.7 (s, C-10), 117.8 (s, C-6b), 119.9–121.1 (d, J 160 Hz, C-3, C-4), 127.8 (d, J 160 Hz, C-2, C-5), 131.8–134.3 (sd, C-6a, C-12a), 134.6 (s, C-3a), 135.2 (dd, J 166, 4.2 Hz, C-11), 150.2 (s, C-7a), 165., 168.3 (sm, OC), 170.1 (sm, CO) (Found: m/z, 450.1775. C25H26N2O6 requires Mr 450.1790). Ethyl 10-acetyl-9-(2-oxopropyl)-7,9-dihydropyrido[1,2-a]perimidine- 8-carboxylate 7b was prepared from but-3-yn-2-one 3b (0.56 g, 8.2 mmol) as a colourless powder, mp=182–184 °C (from CH2Cl2–MeCN, 19:1 as eluent, Rf 0.36), 50% yield; dH (CDCl3, 300 MHz) 1.39 (t, 3 H, J 7 Hz), 2.16 (s, 3 H), 2.34 (s, 3 H), 2.72 (2Åd, 2 H), 4.28–4.29 (2Åq, 2 H, J 7 Hz), 5.88 (2Åd, 1 H, J 7 Hz), 6.59 (dd, 1 H, J 7, 1.5 Hz), 7.05 (d, 1 H, J 7 Hz), 7.22 (s, 1 H, H-4), 7.22 (m, 4 H, Ar), 7.78 (s, 1 H, �CH), 12.32 (br s, 1 H, NH); dC (CDCl3, 75 MHz) 14.6 (qt, J 127, 2.5 Hz), 24.1–31.2 (2Åq, J 127 Hz), 45.5 (tm, J 130 Hz), 49.3 (dq, J 147 Hz), 60.3 (tq, J 147, 4.5 Hz), 82.2 (sd, J 2.7 Hz, C-8), 105.6 (dm, J 160 Hz, C-6), 106.4 (dd, J 160 Hz, C-1), 116.3 (sm, C-6b), 118.0 (sq, C-10), 120.3–121.4 (dm, J 160 Hz, C-3, C-4), 127.9–128.0 (d, J 160 Hz, C-2, C-5), 131.6–134.7 (sd, C-6a, C-12a), 134.7 (sm, C-3a), 136.9 (dd, J 162, 3.8 Hz, C-11), 150.2 (st, C-7a), 168.1 (sm, CO), 193.4 (sm, CO), 205.4 (sm, CO) (Found: m/z, 390.1552.C23H22N2O4 requires Mr, 390.1580). Ethyl 4-(2,3-Dihydro-1H-perimidin-2-ylidene)-4-ethoxycarbonylbut- 2-enoate 5a.·Ethyl 1H-perimidine-2-acetate 3 (1 g, 3.9 mmol) and ethyl propiolate 4a (0.42 g, 4.3 mmol) were added to dry methanol (10 ml) and the mixture refluxed at 65 °C for 3 h with vigorous magnetic stirring.The methanol was removed in vacuo and the crude reaction mixture was triturated with dry diethyl ether (20 ml). After standing (1 h), the precipitated product was filtered off, washed with diethyl ether (2Å10 ml) and dried in a dessicator over CaCl2 to afford compound 5a (0.94 g, 67%); dH ([2H6]DMSO, 300 MHz) d 1.26 (2Åt, 6 H, J 7 Hz), 4.14 (2Åq, 4 H, J 7 Hz), 6.12 (d, 1 H, �CH, J 15 Hz), 6.76 (m, 2 H, H-4, H-9), 7.15 (m, 4 H, Ar), 7.70 (d, 1 H, �CH, J 15 Hz), 11.40 (br s, 2 H, NH); dC ([2H6]DMSO, 75 MHz) 14.2 (qt, J 127, 2.5 Hz), 14.4 (qt, J 127, 2.5 Hz), 58.6 (tq, J 148, 4.8 Hz), 59.4 (tq, J 148, 4.8 Hz), 79.7 (s, Cb), 106.1 (dm, J 163 Hz, �CH), 108.0 (dd, J 166, 5.1 Hz, C-4, C-9), 115.6 (sm, C-9b), 119.1 (dm, J 160 Hz, C-5, C-8), 127.9 (d, J 159 Hz, C-6, C-7), 133.5–133.6 (s, C-3a, C-9a, C-6a), 137.5 (d, J 148 Hz, �CH), 152.4 (s, C-2), 168.5 (sd, CO), 169.5 (sd, J 9 Hz, �CH·CO) (Found: m/z, 352.1432.C20H20N2O4 requires Mr 352.1423). We are indebted to Prolabo for financial support (to F. C.) and thank Dr Jacques Perrocheau for helpful NMR discussions. Received, 10th October 1996; Accepted, 6th February 1997 Paper F/7/01052D References 1 S. M. Weinreb and R.R. Staib, Tetrahedron, 1982, 38, 3087. 2 (a) D. L. Boger and S. M. Weinreb, in Hetero Diels–Alder Methodology in Organic Synthesis, Academic Press, San Diego, 1987; (b) D. L. Boger, in Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, vol. 5, ch. 4.3. 3 (a) M. Teng and F. W. Fowler, J. Org. Chem., 1990, 55, 5646; (b) M. E. Jung and Y. M. Choi, J. Org. Chem., 1991, 56, 6729. 4 (a) D. L. Boger and A. M. Kasper, J. Am. Chem. Soc., 1989, 111, 1517; (b) D.L. Boger, K. C. Kassidy and S. Nakohara, J. Am. Chem. Soc., 1993, 115, 10732. 5 M. Chigr, M. Fillion and A. Rougny, Tetrahedron Lett., 1988, 29, 5913. 6 C. Trione, L. M. Toledo, S. D. Kuduk, F. W. Fowler and D. S. Grierson, J. Org. Chem., 1993, 58, 2075. 7 (a) M. Sakamoto, A. Nozoka, M. Shimamoto, H. Ozaki, Y. Suzuki, S. Yoshioka, M. Nagamo, K. Okamura, T. Date and O. Tamura, Chem. Pharm. Bull., 1994, 42, 1637; (b) J. Chem. Soc., Perkin Trans. 1, 1995, 1759; (c) M.Sakamoto, M. Nagamo, Y. Suzuki, K. Satoh and O. Tamura, Tetrahedron, 1996, 52, 733. 8 A. F. Pozharskii and V. V. Dol’nikovskaya, Russ. Chem. Rev., 1981, 50, 816. 9 S. Rajappa, Tetrahedron, 1981, 37, 1453. 10 F. Cado, P. Jacquault, J. L. Di-Martino, J. P. Bazureau and J. Hamelin, Bull. Soc. Chim. Fr., 1996, 133, 587. 11 F. Cado, J. P. Bazureau and J. Hamelin, Bull. Soc. Chim. Belg., 1996, 105, 273. 12 P. Jacquault, F. Texier-Boullet, J. P. Bazureau and J. Hamelin, International Chemical Congress of Pacific Basin Societies, Honolulu, Hawaii, 17–22 December 1995. 13 (a) R. Commarmot, R. Didenot and J. F. Gardais, Fr. Demande, 2 560 529 (Cl.B01J19/12), 06 Sep. 1985, Appl. 84/3,496, 02 Mar 1984 (Chem. Abstr., 1986, 105, 17442e) [apparatus commercialized by Prolabo (Fr) under the name Synthewave 402®]; (b) temperature measured by an IR captor: Prolabo, Fr. Pat. 62241D, 14669Fr, 23 Dec. 1991. 14 R. C. F. Jones and M. J. Smallridge, Tetrahedron Lett., 1988, 29, 5005 and references cited therein. 15 S. D. Pollington, G. Bond, R. B. Moyes, D. A. Whan, J. P. Candlin and J. R. Jennings, J. Org. Chem., 1991, 56, 1313. Table 2 Synthesis of 7a using an oil bath or under focused microwave irradiation (mw) Yield (%)a Reaction Entry t/min conditions 3 5a 7a 1d 23 e 4e 5e 6e 88 35 35 40 40 mwb oil bathc mw oil bath EtOH/mw EtOH/oil bath R2 R2 R2 R2 38 38 0000 38 38 98 98 98 98 24 24 aYield of crude product estimated by 1H NMR. bReactions were run in a focused microwave oven (Synthewave 402®). cIn a thermostatted oil bath, temperature variation �1 °C. a110 °
ISSN:0308-2342
DOI:10.1039/a701052d
出版商:RSC
年代:1997
数据来源: RSC
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14. |
Facile Synthesis of 2-SubstitutedNaphtho[2,1-b]pyran-3-ones usingMicrowaves† |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 178-179
Mazaahir Kidwai,
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摘要:
CHO OH RCH2CO2H + 1–5 O O R 6–10 N S N Me S N N N N NH N O N Me O 1,6 2,7 3,8 4,9 5,10 R R 178 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 178–179† Facile Synthesis of 2-Substituted Naphtho[2,1-b]pyran- 3-ones using Microwaves† Mazaahir Kidwai* and Parven Kumar Department of Chemistry, Delhi University, Delhi-110007, India 2-Substituted naptho[2,1-b]pyran-3-ones have been synthesised by a novel one-pot method which involves cyclocondensation of 2-hydroxy-1-naphthaldehyde with 5-methyl-1,3,4-thiadiazol-2-ylsulfanyl-, 1H-1,2,3,4-tetrazol-1-yl-, 1H-indol-3-yl-, quinolin-8-yloxy- and 4-methylquinolin-2-yloxy-acetic acids in the presence of DCC–DMSO using microwaves as well as conventional heating.Nowadays there is considerable interest in the rapid synthesis of a variety of heterocyclic compounds under microwave irradiation in domestic microwave ovens.1 In continuation of our work on microwave-assisted synthesis2,3 we report herein a new facile method for the synthesis of 2-(5-methyl- 1,3,4-thiadiazol-2-ylsulfanyl)-, 2-(1H-1,2,3,4-tetrazol-1-yl)-, 2-(1H-indol-3-yl)-, 2-(quinolin-8-yloxy)- and 2-(4-methylquinolin- 2-yloxy)-naphtho[2,1-b]pyran-3-ones in the presence of dicyclohexylcarbodimide (DCC) and dimethyl sulfoxide (DMSO) using conventional heating as well as microwave irradiation.Thiadiazole,4 tetrazole,4 indole5 and quinoline6 derivatives are well known for their biological importance. Naptho[2,1- b]pyran-3-ones have shown antimicrobial,7 antiinflammatory8 and anticancer9 activities.In view of the biological importance of the above-mentioned species and the importance of MORE (microwave-induced organic reaction enhancement) chemistry, we thought it worthwhile to develop a new method for rapid synthesis of the title compounds incorporating thiadiazole, tetrazole, indole and quinoline rings and to screen the products for biological activity. 5-Methyl-1,3,4-thiadiazol-2-ylsulfanyl-, quinolin-8-yloxyand 4-methylquinolin-2-yloxy-acetic acids were prepared starting from 5-methyl-1,3,4-thiadiazole-2-thiol, 8-hydroxyquinoline and 2-hydroxy-4-methylquinoline respectively by treatment with ethyl bromoacetate3 followed by hydrolysis of the ester using aqueous KOH to give the corresponding acid (1, 4, 5). 1H-1,2,3,4-Tetrazol-1-yl- and 1H-indol-3-yl-acetic acids (2, 3) are commercially available. 2-Hydroxy-1-naphthaldehyde was condensed with an appropriate substituted acetic acid (1–5) in the presence of DCC using DMSO as solvent to obtain the corresponding naphtho[2,1-b]pyran-3-ones (6–10).In the classical approach, cyclocondensation of an aldehyde with acids 1–5 requires 18–20 h, with heating at 100–120 °C. Some impurities also formed in the final hours of the reactions. In contrast, the same reaction required 6–8 min when carried out under microwave irradiation and no such impurities were observed. No appreciable differences in yields of reactions were observed.The title compounds were characterised on the basis of analytical and spectral data (Experimental section). The IR spectra showed absorption at 1710–1730 cmµ1 due to the lactone of the coumarin ring. In the 1H NMR spectra, a singlet at d 8.3–8.5 was assigned to the 1-H proton of the naphtho[2,1-b]pyran-3-one ring. The reaction is depicted in Scheme 1. Experimental Mps (uncorrected) were recorded on an Electrothermal apparatus. IR (KBr) were recorded on a Perkin-Elmer spectrometer (model 599) and 1H NMR spectra were recorded on a Hitachi R-600 FT spectrometer using Me4Si as internal standard.Mass spectra were recorded on a JEOL-JMS-DX 303 mass spectrometer. The purities of the compounds were checked on silica gel coated Al plates (Merck). General Procedure for Synthesis of Naphtho[2,1-b]pyran-3-ones (6–10).·2-Hydroxy-1-naphthaldehyde (5 mmol, 0.86 g), the appropriate substituted acetic acid (6.25 mmol) and DCC (7.8 mmol, 1.6 g) were mixed in DMSO (16 ml) in a 100 ml conical flask covered with a funnel.The reaction mixture was irradiated in a microwave oven at low power setting. TLC was run after every 2 min to check the progress of the reaction. Once reaction was complete (in 8–10 min), the reaction mixture was treated with 15% aqueous acetic acid (100 ml) and stirred for 2 h before extraction with diethyl ether (2Å50 ml). Dicyclohexylurea which separated at the interface of the two layers was removed by filtration. The organic layer was washed with 5% NaHCO3 (50 ml) and 5% sodium metabisulfite (50 ml) solution to remove unreacted acid and 2-hydroxy-1-naphthaldehyde respectively. Finally, the ether layer was washed with water, dried over Na2SO4 (anhydrous) and evaporated to afford a residue which was triturated with benzene– ethyl acetate to afford the corresponding naptho[2,1-b]pyran- 3-ones. 2 - ( 5 - M e t h y l- 1 , 3 , 4 - t h i a d i a z o l - 2 - y l s u l f a n y l ) n a p h t h o [ 2 , 1 - b ]p y r a n - 3-one (6), yield 67%, had mp 213–214 °C; vmax/cmµ1 1710 (lactone of coumarin); dH (CDCl3+[2H6]DMSO) 2.72 (3 H, s, CH3 ring), 7.15–8.19 (6 H, m, arom.), 8.41 (1H, s, 1-H); m/z 326 (M+) (Found: C, 58.75; H, 3.10; N, 8.55.C16H10N2O2S2 requires C, 58.89; H, 3.06; N, 8.58%). 2-(1H-1,2,3,4-Tetrazol-1-yl)naptho[2,1-b]pyran-3-one (7), yield 61%, had mp 234–235 °C; vmax/cmµ1 1720 (lactone of coumarin); dH (CDCl3+[2H6]DMSO) 7.12–8.31 (6 H, m, arom.), 8.53 (1 H, s, 1-H), 9.51 (1 H, s, 5p-H of tetrazole ring); m/z 264 (M+) (Found: C, 63.80; H, 3.08; N, 21.24.C14H8N2O2 requires C, 63.63; H, 3.03; N, 21.21%). 2-(1H-Indol-3-yl)naphtho[2,1-b]pyran-3-one (8), yield 58%, had mp 208 °C; vmax/cmµ1 1715 (lactone of coumarin); dH (CDCl3+[2H6]DMSO) 7.18–8.19 (11 H, m, arom.), 8.35 (1 H, br s, NH), 8.50 (1 H, s, 1-H); m/z 311 (M+) (Found: C, 80.82; H, 4.19; N, 4.54. C21H13NO2 requires C, 81.02; H, 4.18; N, 4.50%). 2-(Quinolin-8-yloxy)naphtho[2,1-b]pyran-3-one (9), yield 64%, had mp 179–180 °C; vmax/cmµ1 1710 (lactone of coumarin); dH (CDCl3+[2H6]DMSO) 7.13–8.21 (12 H, m, arom.), 8.32 (1 H, s, *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 1J. CHEM. RESEARCH (S), 1997 179 1-H); m/z 339 (M+) (Found: C, 77.74; H, 3.80; N, 4.11.C22H13NO3 requires C, 77.87; H, 3.83; N, 4.12%). 2 - ( 4 - M e t h y l q u i n o l i n - 2 - y l o x y )n a p h t h o [ 2 , 1 - b ] p y r a n - 3 - o n e ( 1 0 ) , yield 60%, had mp 202–203 °C; vmax/cmµ1 1720 (lactone of coumarin); dH (CDCl3+[2H6]DMSO) 2.40 (3 H, s, CH3 ring), 7.18–8.06 (11 H, m, arom.), 8.5 (1 H, s, 1-H); m/z 353 (M+) (Found: C, 78.02; H, 4.26; N, 3.99. C23H15NO3 requires C, 78.18; H, 4.24; N, 3.96%). We are grateful to the University Grant Commission for financial support. Received, 22nd January 1997; Accepted, 17th February 1997 Paper E/7/00516D References 1 S. Caddick, Tetrahedron, 1995, 51, 10403. 2 M. Kidwai and P. Kumar, J. Chem. Res. (S), 1996, 254. 3 M. Kidwai and Y. Goel, Polyhedron, 1996, 15, 2819. 4 K. Kariyone, H. Harada, M. Kurita and T. Takano, J. Antibiot., 1970, 23, 131. 5 M. Kidwai, N. Negi and S. D. Gupta, Chem. Pharm. Bull., 1994, 42, 2363. 6 M. Kidwai, N. Negi and S. R. Chowdhbury, Acta Pharm., 1995, 45, 511. 7 A. Hammad, A. S. El-Sayed, I. E. Islam and N. Shafik, J. Chem. Soc. Pak., 1990, 12, 292 (Chem. Abstr., 1990, 115, 71479S). 8 G. M. Kulkarni, H. V. Kulkarni, V. D. Patil, D. B. Shridhar and M. Laxmana, Rev. Roum. Chim., 1990, 35, 549. 9 R. G. Harvey, C. Cortex, T. P. Ananthanarayan and S. Schmolka, J. Org. Chem., 1988, 53, 3936.
ISSN:0308-2342
DOI:10.1039/a700516d
出版商:RSC
年代:1997
数据来源: RSC
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15. |
Efficient Nucleophilic Cleavage of Oxiranes toChlorohydrins† |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 180-180
Chintamani Sarangi,
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摘要:
O R1 R2 SnCl2•2H2O–Mg THF–H2O Cl OH R2 R1 O O O O PhCH CH2 O PhCH CHPh O PhOCH2CH CH2 O ClCH2CH CH2 O OH Cl Cl OH Cl OH Cl OH Cl CHCH2OH Ph Cl CHCHOH OH Ph OH CHCH2Cl PhOCH2 OH CHCH2Cl ClCH2 180 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 180† Efficient Nucleophilic Cleavage of Oxiranes to Chlorohydrins† Chintamani Sarangi,a Nalin B. Das,*a Bhagabat Nanda,a Amaendu Nayaka and Ram P. Sharmab aRegional Research Laboratory, Bhubaneswar-751013, India bCentral Institute of Medicinal and Aromatic Plants, Lucknow-226015, India SnCl2 .2H2O–Mg and THF–H2O is an efficient system for the conversion of oxiranes into chlorohydrins.Epoxides are valuable intermediates in organic synthesis partly because of their nucleophilic cleavage leading to 1,2-difunctionalized systems and partly because such cleavages usually occur specifically with trans stereochemistry. The formation of halohydrins from epoxides has been extensively studied with a variety of reagents.1–8 Although there is precedent for the Lewis acid assisted cleavage of oxiranes to halohydrins, these reactions often afford only modest yields.The present work was undertaken in order to determine the general applicability of the reaction with epoxides. In continuation of our earlier studies on the uses of metal reagents,9,10 we found that SnCl2 .2H2O–Mg and THF–H2O is a promising system for the regioselective ring opening of oxiranes to the corresponding chlorohydrins in good yields.In acidic medium1 there is usually a greater tendency for nucleophilic attack at the more substituted carbon atom. Phenyl substituents at the epoxide ring can stabilize an intermediate positive charge by conjugation, and hence attack occurs at the more substituted carbon atom. However, in the case of epoxides with electron withdrawing substituents, nucleophilic attack at the unsubstituted carbon is usually favoured. Under these conditions, substituted epoxides (Table 1, entries 4, 7 and 8) reacted regioselectively affording the primary chloride.The cyclohexene oxide and the epoxide (entries 2 and 3 respectively) opened cleanly to afford the trans chlorohydrins, with the tertiary chloride being the major product in the latter case. However in the case of styrene oxide the secondary chloride predominates. The yield of the products corresponds to the total yield of the regioisomers. Cleavage of the oxirane ring has also been unsuccessfully attempted using SnCl2 .2H2O–THF alone.However, the use of a stoichiometric amount of magnesium facilitated the reaction. In addition, the possibility of active zero-valent tin (generated in situ by the reduction of SnII to Sn0 in the presence of magnesium) could effectively induce regioselective nucleophilic attack. Owing to the general interest in the smooth and selective cleavage of these compounds, mild reaction conditions, good yields and some possible synthetic applications, the SnCl2 .2H2O–Mg–THF system will be a useful addition to the existing findings.Experimental 1H NMR spectra were recorded on deuteriochloroform on a JEOL FX-90 instrument. IR spectra were recorded on a JASCO FT/IR-5300 instrument in chloroform. Mass spectra were recorded on an MS-30 instrument. TLC and preparative TLC were performed on silica gel (E. Merck). General Procedure.·In a typical procedure, a mixture of SnCl2.2H2O (442 mg, 2 mmol), Mg powder (36.5 mg, 1.5 mmol) and oxirane (1 mmol) in THF (10 ml) was stirred at room temperature.An exothermic reaction occurred with the liberation of hydrogen. The reaction mixture was stirred for 30 min. After completion of the reaction (TLC), usual work-up and purification by preparative chromatography yielded the corresponding chlorohydrins. Selected 1H NMR spectral data. For trans-2-chlorocyclohexanol: dH (CDCl3) 1.1–1.95 (8 H, m), 2.65 (1 H, br s), 3.05–3.5 (2 H, m). For 1-chloromethylcyclohexanol: dH (CDCl3) 1.2–1.75 (10 H, m), 2.15 (1 H, br s), 3.15 (2 H, s).For 1-chlorohexan-2-ol: dH (CDCl3) 1.15 (3 H, s), 1.35–1.95 (6 H, m), 2.6 (1 H, br s), 3.8 (2 H, d), 4.85 (1 H, t). For 2-chloro-2-phenylethanol: dH (CDCl3) 2.36 (1 H, s), 3.95–1.95 (2 H, d), 5.05 (1 H, t), 7.48 (5 H, m). We thank Professor H. S. Ray, Director, and Dr Y. R. Rao, Head, F&M Division, Regional Research Laboratory, for their valuable suggestions. C. S. acknowledges the pool scheme of the Government of India.Received, 18th November 1996; Accepted, 11th February 1997 Paper E/6/07796J References 1 J. G. Smith, Synthesis, 1984, 629. 2 H. O. House, Modern Synthetic Reactions, Benjamin, Menlo Park, 1972, p. 301. 3 M. A. Loreto, L. Pellacani and P. A. Tardella, Synth. Commun., 1981, 11, 287. 4 J. Kagan, B. E. Firth, N. Y. Shih and C. G. Boyajian, J. Org. Chem., 1977, 42, 343. 5 E. Mincione, G. Ortaggi and A. Sirna, J. Org. Chem., 1979, 44, 1569. 6 T. W. Bell and J. A. Ciaccio, Tetrahedron Lett., 1986, 27, 827. 7 C. L. Spawn, G. J. Drtina and D. F. Weiner, Synthesis, 1986, 315. 8 C. Einhorn and J. L. Luche, J. Chem. Soc., Chem. Commun., 1986, 1368 and references cited therein. 9 C. Sarangi, A. Nayak, B. Nanda, N. B. Das and R. P. Sharma, Tetrahedron Lett., 1995, 36, 7119. 10 C. Sarangi, A. Nayak, B. Nanda, N. B. Das and R. P. Sharma, J. Chem. Res. (S), 1996, 28 and references cited therein. *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 Oxirane ring opening with SnCl2.2H2O–Mg–THF–H2O Entry Oxirane Producta Yield (%)b 1 64 2 72 3 75 4 77 5 90 6 78 7 86 8 74 aAll the products gave satisfactory spectral data. bTotal yield of the regioisomers.
ISSN:0308-2342
DOI:10.1039/a607796j
出版商:RSC
年代:1997
数据来源: RSC
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16. |
Simple Routes to Keto-norsteroids |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 221-221
James R. Hanson,
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摘要:
Simple Routes to Keto-norsteroids James R. Hanson* and Cavit Uyanik School of Chemistry, Physics and Environmental Science, University of Sussex, Brighton, Sussex BN1 9QJ, UK Ring A and B keto-norsteroids have been obtained by applying the McMurray low valency titanium cyclization to steroidal seco ring A and ring B nor-keto-esters which were readily available by cleaving the corresponding unsaturated ketones. Nor-steroids often have an interesting pharmacological proRle when compared to their six-membered analogues.1 The established methods2 for the preparation of keto- norsteroids involve a series of steps which do not always proceed in good yield.Here we describe simple alternative routes to these compounds utilizing the McMurray reac- tion.4 Oxidative cleavage of steroidal D4-3-ketones 1 with potassium permanganate�}sodium periodate a€orded the 5-oxo-3,5-seco-4-nor-3-oic acids 2 in good yield. The acids were methylated with caesium �Puoride and methyl iodide.6 The resultant keto-esters were then reductively cyclized with a low-valency titanium reagent derived from the titanium trichloride : dimethoxyethane complex and a zinc : copper couple.7 This a€orded the 5b-A-nor-3-ketone 4 as the major product (67%) accompanied by the 3(5)-alkene 3 as the minor product.The sequence was applied to testosterone acetate 1a, 19-nortestosterone acetate 1b, progesterone 1c and cholest-4-en-3-one 1d which were converted to their respective 5b-A-nor-3-ketones 4a�}d together with small amounts of the 3(5)-alkenes.A similar sequence was applied to the preparation of a B-norsteroid. The readily available dehydroisoandro- sterone (3b-hydroxyandrost-5-en-17-one) was converted via its 3b-iodo derivative into androst-5-en-17-one 5.9 The latter was oxidized with the chromium trioxide�}3,5-dimethyl- pyrazole complex10 to androst-5-en-7,17-dione 6. Cleavage of the unsaturated ketone with potassium permanganate�} sodium periodate and methylation with caesium �Puoride�} methyl iodide gave methyl 5,17-dioxo-5,7-seco-6-nor- androstan-7-oate 7.This keto-ester was reductively cyclized with low valency titanium to the B-norketone. The major product (47%) was the B-nor-5a-androstan-6,17-dione 8 accompanied by the cis isomer 9 (15%). C.U. wishes to thank Kocaeli University, Izmit, Turkey, for study leave and Rnancial assistance. Techniques used: IR, 1H NMR, chromatography References: 15 Received, 25th November 1997; Accepted, 30th December 1997 Paper E/7/08520F References cited in this synopsis 1 P.G. Marshall, in Rodd's Chemistry of Carbon Compounds, ed. S. Co€ey, Elsevier, Amsterdam, 1970, vol. IID, p. 281. 2 For a review see: R. M. Scribner, in Organic Reactions in Steroid Chemistry, ed. J. Fried and J. A. Edwards, van Nostrand:Reinhold, New York, 1972, vol. 2, p. 408. 4 A. Furstner and B. Bogdanovic, Angew. Chem., Int. Ed. Engl., 1996, 35, 2442. 6 T. Sato, J. Otera and H. Nozaki, J. Org. Chem., 1992, 57, 2166. 7 J. McMurray, T. Lectka and J. G. Rico, J. Org. Chem., 1989, 54, 3748. 9 J. R. Hanson, H. J. Wadsworth and W. E. Hull, J. Chem. Soc., Perkin Trans. 1, 1988, 1381. 10 W. G. Salmond, M. A. Barta and J. Havens, J. Org. Chem., 1978, 43, 2057. J. Chem. Research (S), 1998, 221 J. Chem. Research (M), 1998, 1032�}1042 *To receive any correspondence. J. CHEM. RESEAR
ISSN:0308-2342
DOI:10.1039/a704747i
出版商:RSC
年代:1998
数据来源: RSC
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17. |
Semiempirical andAb InitioCalculations of Tautomerism in 2,3-Dihydroxypyrazine |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 222-223
Ahmed M. El-Nahas,
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摘要:
Semiempirical and Ab Initio Calculations of Tautomerism in 2,3-Dihydroxypyrazine Ahmed M. El-Nahas Chemistry Department, Faculty of Science, El-Menou�¡a University, Shebin El-Kom, Egypt Semiempirical (AM1 and PM3) and ab initio (MP2/6-31 a G*//HF/6-31 a G*) calculations on the relative stabilities of different tautomers of 2,3-dihydroxypyrazine show that this species exists not only in solution but also in the gas phase predominantly as a dioxo tautomer. Owing to its signi¢çcance in many chemical and biological reactions, the tautomerism of heterocyclic compounds continues to be a matter of intense experimental and theoretical research.3 Solvent e€ects often play an important role in organic chemistry and many chemical equilibria may be substantially modi¢çed by a change of the molecular environment.23 Most theoretical and experimental studies have concentrated on the tautomerism in 2-hydroxypyridine, uracil, thymine and cytosine.8¡¾13 A theoretical study28 at the AM1 and 3-21G levels on the tautomerism of hydroxy- pyrazine and mercaptopyrazine has shown that hydroxy- pyrazine and its oxo form are present in almost equal proportions while the thiol is of greater concentration than the thione.To our knowledge there previously have been neither theoretical nor experimental investigations involving 2,3-dihydroxypyrazine. A similar compound, 2,3- dioxopiperazine, has been studied both experimentally and theoretically and it was found that the dioxo form is the most stable species in the solid state.29 In this regard, it appeared interesting to study tautomerism in 2,3-dihydroxy- pyrazine.This compound can exist in three tautomeric forms, two of which exist in more than one conformer (Fig. 1). Our aim in this study is to use semiempirical (AM11 and PM32) and ab initio calculations to predict the stabilities of the 2-hydroxy-3-oxo and 2,3-dioxo tautomers of 2,3-dihydroxypyrazine. The geometries of the investigated tautomers were optimized at the AM1 and PM3 levels in the gas phase and in aqueous solutions without any symmetry constraints.Solvent e€ects in aqueous solution are calculated using the Self-Consistent Reaction Field (SCRF) method24 available in the VAMP5.5 program.33 The optimizations of the molecular geometries were carried out within C2v (1, 3, 6) and Cs (2, 4, 5) symmetries using the Hartree¡¾Fock method37 with the 6-31 a G* basis set.38 The e€ect of electron correlation on the calculated relative energies was investigated by performing Moeller¡¾Plesset calculations40 truncated at second order (MP2) with the 6-31 a G* basis set.Relative energies for the structures displayed in Fig. 1 are listed in Table 2. A plot of relative energies at di€erent theoretical levels in the gas phase and in aqueous solution is shown in Fig. 2. Compared to HF/6-31 a G*, the average errors in calculating di€erent properties using AM1 and PM3 procedures are given in Table 4.All calculated forms of 1, 2, 4, 5, 6 (Fig. 1) are minima on the potential energy surface of 2,3-dihydroxypyrazine, while structure 3 is a saddle point of second order and is, therefore, removed from further discussion. The energy J. Chem. Research (S), 1998, 222¡¾223 J. Chem. Research (M), 1998, 1014¡¾1031 Fig. 1 Optimized conformations of 2,3-dihydroxypyrazine Table 4 Absolute errors in relative energies (kcal mol¢§1), dipole moments (Debye), and ionization potentials (eV) obtained from AM1 and PM3 methods in the gas phase (w.r.t. 6-31 a G*) RE (kcal mol¢§1) DM (Debye) IP (eV) Structure AM1 PM3 AM1 PM3 AM1 PM3 1 0.0 0.0 0.088 0.172 0.278 0.402 2 0.18 0.74 0.529 0.830 0.331 0.412 3 4.52 9.81 0.961 0.390 0.408 0.476 4 1.01 2.28 0.594 0.923 0.129 0.129 5 3.21 3.80 0.384 0.980 0.128 0.096 6 1.28 4.00 1.206 1.981 0.164 0.152 Average errors 1.77 3.44 0.627 0.879 0.240 0.278 Table 2 Relative energies (kcal mol¢§1) for the investigated molecule at semiempirical and ab initio levels Gas phase Aqueous solution Structure AM1 PM3 AM1 PM3 6-31 a G* MP2/6-31 a G*//HF/6-31 a G* 1 0.0 0.0 0.0 0.0 0.0 0.0 2 1.19 0.63 ¢§1.12 ¢§1.15 1.37 1.02 3 10.63 5.34 4.84 0.10 15.15 14.16 4 ¢§0.65 0.62 ¢§4.92 ¢§3.45 ¢§1.66 0.86 5 ¢§0.30 0.29 ¢§4.98 ¢§3.69 ¢§3.51 ¢§1.49 6 ¢§7.24 ¢§4.52 ¢§13.31 ¢§10.12 ¢§8.52 ¢§3.82 222 J.CHEM. RESEARCH (S), 1998barrier required for transformation of the dihydroxy forms 1 to 2 amounts to 3 kcal mol¢§1 while that for conversion of the dihydroxy 1 to the hydroxyoxo 4 tautomer is 143 kcal mol¢§1, at the AM1 level in the gas and liquid phases.Inspection of Fig. 2 shows that the dioxo tautomer 6 is the most stable species at all the theoretical levels while the relative stabilities of the hydroxyoxo forms 4, 5 depend on the calculational level, as these are close enough energetically. In polar solvents, the tautomeric equilibrium of 2,3- dihydroxypyrazine is shifted in favor of the more polar oxo forms.22,41 The dioxo form 6 was found to be the most stable structure, with the stability in solution increased by 16 kcal mol¢§1 compared to that found in the gas phase.In solvents of high relative permittivity, the stability of the hydroxyoxo forms 4, 5 also increases, which indicates that 2,3-dihydroxypyrazine is present in solution predomi- nantly as hydroxyoxo and dioxo tautomers. These results may explain the predominance of the similar compound, 2,3-dioxopiperazine, in the solid state.29 The a-diketone is thus stable in the gas and condensed phases and can undergo condensation and other reactions at the carbonyl groups.Fig. 2 Plot of relative energies versus theoretical levels. All energies are relative to that of 1. SCF represents HF/6-31 a G* and MP2 represents MP2/6-31 a G*//HF/6-31 a G* The author thanks Professor P. v. R. Schleyer for facili- tating ab initio calculations at Erlangen, Germany. Techniques used: Semiempirical (AM1 and PM3), ab initio and self- consistent reaction ¢çeld theory calculations.References: 43 Table 1: Heats of formation (AM1 and PM3, in kcal mol¢§1) and total energies (ab initio, in a.u.) for the investigated species Table 3: Dipole moments (Debye) and ionization potentials (eV) for the investigated species in the gas phase Table 5: Optimized geometries for di€erent structures in the gas phase Received, 18th August 1997; Accepted, 22nd December 1997 Paper E/7/06037H References cited in this synopsis 1 M.J. S. Dewar, E. G. Zoebisch, E. F. Healy and J. J. P. Stewart, J. Am. Chem. Soc., 1985, 107, 3902. 2 J. J. P. Stewart, J. Comput. Chem., 1989, 10, 209, 221. 3 J. S. Kwaitowski, T. J. Zielinski and R. Rein, Adv. Quant. Chem., 1986, 18, 85. 8 W. M. F. Fabian, J. Phys. Org. Chem., 1990, 3, 332. 9 W. M. F. Fabian, J. Mol. Struct. (Theochem), 1990, 206, 295. 10 J. Leszczynski, J. Phys. Chem., 1992, 96, 1649. 11 H. Meghezzi and A.Boucekkine, J. Mol. Struct. (Theochem), 1992, 257, 175. 12 U. Narinder, J. Mol. Struct. (Theochem), 1989, 188, 199. 13 A. R. Katritzky, M. Szafran and J. Stevens, J. Mol. Struct. (Theochem), 1989, 184, 179. 23 C. Reichardt, in Solvent and Solvent E€ects in Organic Chemistry, VCH, Weinheim, 1988. 24 G. Rauhut, T. Clark and T. Steinke, J. Am. Chem. Soc., 1993, 115, 9174. 28 J. G. Contreras and J. B. Alderete, Bol. Soc. Chil. Quim., 1992, 37, 7. 29 A. Peeters, C. V. Alesony, A. T. H. Lenstra and H. G. Geise, Int. J. Quant. Chem., 1993, 46, 73. 33 G. Rauhut, A. Alex, J. Chandrasekhar and T. Clark, in VAMP5.5, Oxford Molecular Ltd., Oxford, 1993. 37 C. C. J. Roothaan, Rev. Mod. Phys., 1951, 23, 69. 38 (a) P. C. Harriharan and J. A. Pople, Theor. Chim. Acta, 1973, 28, 213; (b) T. Clark, J. Chandrasekhar, G. W. Spitznagel and P. v. R. Schleyer, J. Comput. Chem., 1983, 4, 294. 40 (a) C. Moeller and M. S. Plesset, Phys. Rev., 1934, 46, 618; (b) J. A. Pople, J. S. Binkley and R. Seeger, Int. J. Quant. Chem., 1976, 10, 1. 41 (a) J. Frank and A. R. Katritzky, J. Chem. S., Perkin Trans. 2, 1976, 1428; (b) M. Kuzuya, A. Noguchi and T. Okuda, J. Chem. Soc., Perkin Trans. 2, 1985, 1423. J. CHEM. RESEARCH (S), 1998 223
ISSN:0308-2342
DOI:10.1039/a706037h
出版商:RSC
年代:1998
数据来源: RSC
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18. |
Preparation of some Quinoxaline Quinones, their Electrochemical Reduction, and EPR and Theoretical Studies on their Semiquinone Anions |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 224-225
Sean L. W. McWhinnie,
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摘要:
Preparation of some Quinoxaline Quinones, their Electrochemical Reduction, and EPR and Theoretical Studies on their Semiquinone Anions Sean L. W. McWhinnie,a Abid R. Ahmad,a Luis P. Candeias,b Lina K. Mehta,a John Parrick*a and Eric L. Shorta aDepartment of Chemistry, Brunel University, Uxbridge, Middlesex UB8 3PH, UK bGray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, UK Novel 2,3-disubstituted quinoxaline quinones and a tricyclic quinone containing the quinoxaline nucleus are reported together with their one-electron reduction chemistry and the EPR spectra of the radical anions. The 2,3-substituents on quinoxaline quinones have an e€ect on the stability of the compounds.This is indicated by the observation that the parent quinone 1 is not stable and is best prepared immediately before use whereas the 2,3-bis(ethylsulfanyl)- and 2,3-dimethoxy-quinoxaline-5,8- quinones, 2 and 3, respectively are relatively stable in air and can be left in the solid state in the dark for a month or more without signi¢çcant decomposition.Our investigations were undertaken in order to gain more understanding of the e€ects produced by substituents at the 2- and 3-positions of the quinoxaline quinone nucleus on the ease of reduction of the quinone (Q) and the properties of the radical anion (Q ¢§ ) (Fig. 1). The present study was carried out using DMF as the solvent since semiquinones are more stable in aprotic solvents than in water.5 Good correlations exist between E(Q/Q ¢§ ) in water and in DMF.The tetrachloroquinoxaline quinone 5 was obtained from 5,8-dimethoxyquinoxaline 417 by oxidation with a mixture of concentrated nitric and hydrochloric acids, and the tetra- methoxyquinoxaline quinone 6 was formed by the action of sodium methoxide in methanol on 5 (Scheme 1). Reaction of 4 with 2 equiv. of disodium ethylene glycolate gave both 7 and 8, and 8 was also readily prepared from 7 by the action of sodium hydride in DMSO (Scheme 2).6 The tetra- methoxyquinoxaline 10 was available from 4.Oxidation of 5,8-dimethoxyquinoxalines 8, 9 and 10 to the corresponding quinones 11, 2 and 3 was achieved using ammonium cerium(IV) nitrate (CAN) (Scheme 2). The quinones showed a singlet between d 6.90 and 6.95 in their 1H NMR spectra due to the quinone ring hydrogens. This is at higher ¢çeld than for the quinoxaline-5,8-diones 1, 12 and 13 which have a singlet in their NMR spectra in the range d 7.24 to 7.29.The up¢çeld shift for 2, 3 and 11 is probably due to strong electron release from the 2- and 3-substituents. Treatment of the quinone 3 with 1-acetoxybutadiene gave 14 in a process involving both loss of acetic acid and dehydrogenation. The ¢çve compounds studied 2, 5, 6, 11 and 14, dis- played two reversible reduction processes corresponding to the reduction of Q to Q ¢§ and of Q ¢§ to Q2 ¢§ respectively, where Q2 ¢§ is the quinol dianion, with E(Q ¢§/Q2 ¢§ ) ¢§ E(Q/Q ¢§ ) values of between ¢§540 and ¢§700 mV (Table 1).Calculation of comproportion equilibrium constants (Kcom=exp{¢§(F/RT)[E(Q ¢§/Q2 ¢§ ) ¢§ E(Q/Q ¢§ )]}) from these data indicate that the semiquinones are stable with respect to disproportionation (Fig. 1). For comparison, the reduction potentials of 2,3-dichloro- 1,4-naphthquinone under identical conditions were ¢§0.472 and ¢§1.480 V respectively and fall within the range of the values obtained for the quinoxaline quinones so indicating that the nitrogen atoms have little e€ect upon the reduction potentials.Plots of return current against the square root of the scan rate for the ¢çrst reduction processes gave straight lines even when the second reduction was cycled and thus also con¢çrm the reversibility of the couples. The EPR spectra of the radical anions revealed g values of 12.005, typical of organic radicals, and small hyper¢çne J. Chem. Research (S), 1998, 224¡¾225 J.Chem. Research (M), 1998, 1043¡¾1055 Fig. 1 Stepwise one-electron reduction of a para-quinone and the equilibrium between quinone, radical anion and dianion Scheme 1 Reagents and conditions: i, concentrated HCl, concentrated HNO3, r.t., 1.5 h; ii, MeOH, NaOMe, r.t., 1 h Scheme 2 Reagents and conditions: i, HOCH2CH2OH, Na, THF, reflux, 4 h; ii, DMSO, NaH, r.t., 4 h; iii, EtSNa, EtOH, reflux, 2 h; iv, MeOH, NaOMe, r.t., 1 h; v, CAN, MeOH, H2O, ice-bath, 0.5 h *To receive any correspondence. 224 J.CHEM. RESEARCH (S), 1998Table 1 Electrochemical data for compounds 2, 5, 6, 11 and 14a E(Q/Q ¢§ ) E(Q ¢§/Q2 ¢§) E(Q/Q ¢§ ) ¢§ Comproportion equilibrium Compound E1/2/V DEp/mV E1/2/V DEp/mV E(Q ¢§/Q2 ¢§)/V constants 2 ¢§0.91 145 ¢§1.58 675 ¢§0.67 1.91011 5 ¢§0.49 85 ¢§1.19 85 ¢§0.70 6.01011 6 ¢§1.07 110 ¢§1.61 335 ¢§0.54 1.2109 9 ¢§0.96 75 ¢§1.55 195 ¢§0.59 8.4109 14 ¢§1.19 115 ¢§1.77 465 ¢§0.58 5.8109 aConditions are given in the Experimental section (full text).splittings (<1 mT), showing that the hyper¢çne coupling constants of the active nuclei are small. Initial attempts to record the spectrum of compound 5 led to the observation of a weak spectrum without the application of a current due to chemical reduction by the mercury working electrode. Semiempirical INDO calculations were carried out on the radical anions of the quinones as an aid to the assignment of the hyper¢çne coupling constants and in order to obtain their signs.We thank the Government of Pakistan for ¢çnancial support (A.R.A.), Mrs S. Sadiq for the preparation of 14 and Professor P. Wardman for helpful discussions. L.P.C. thanks the Cancer Research Campaign for support. Techniques used: IR, 1H NMR, EPR, mass spectrometry, cyclic voltammetry, INDO calculations References: 17 Schemes: 3 Fig. 2: Some resonance e€ects in 2,3-dimethoxyquinoxaline 5,8- quinone Fig. 3: Cyclic voltammogram of compound 5 at scan rate 200 mV s¢§1 Fig. 4: Cyclic voltammogram of compound 14 at scan rate 200 mV s¢§1 Fig. 5: g Values and hyper¢çne coupling constants of the radical anions of compounds 2, 5, 6, 11 and 14. Calculated hyper¢çne coupling constants are given in parentheses Fig. 6: Experimental and simulated EPR spectra of the radical anion of compound 2, (a) whole spectrum, (b) expansion Fig. 7: Experimental and simulated EPR spectra of the radical anion of compound 14 Received, 29th August 1997; Accepted, 7th January 1998 Paper E/7/06324E References cited in this synopsis 5 A. R. Ahmad, L. K. Mehta and J. Parrick, J. Chem. Soc., Perkin Trans. 1, 1996, 2443. 6 W. F. Gum, Jr. and M. M. JoullieA , J. Org. Chem., 1967, 32, 53. 17 S. Oguchi, Bull. Chem. Soc. Jpn, 1968, 41, 980. J. CHEM. RESEARCH (S), 1998 225
ISSN:0308-2342
DOI:10.1039/a706324e
出版商:RSC
年代:1998
数据来源: RSC
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19. |
Synthesis of Diversely Functionalised Dibenzylbutyrolactones and Aryltetralins from Silylated Cyanohydrin Anions |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 226-227
Robert S. Ward,
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摘要:
Synthesis of Diversely Functionalised Dibenzylbutyrolactones and Aryltetralins from Silylated Cyanohydrin Anions Robert S. Ward,*a Andrew Pelter,a Antonella Brizzi,b Alessandro Segab and Paola Paolic aChemistry Department, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK bIstituto di Chimica Organica dell' Universita di Siena, Pian del Mantellini 44, 53100 Siena, Italy cDipartimento di Energetica, Universita degli Studi di Firenze, Via Santa Marta 3, 50139 Firenze, Italy The aryltetralins 7a and 7b and the keto-lactone 8 are synthesised by cyclisation and deprotection of the conjugate addition products 4a and 4b; the structure of 7b was unambiguously confirmed by an X-ray structural analysis.Following the methodology developed by Iwasaki et al.1�}3 we have shown that tandem conjugate addition by anions derived from tert-butyldimethylsilylcyanohydrins 1 to butenolides proceeds stereoselectively to give dibenzyl- butrolactones 2, which in turn a€ord access to aryltetralin lignans 3 (Scheme 1).4 In order to synthesise di€erentially protected lignans belonging to the dibenzylbutyrolactone and aryltetralin series we have now prepared the tandem conjugate addition product 4 and have examined its reactions with tri�Puoroacetic acid (TFA) and tetrabutyl- ammonium �Puoride (TBAF).The compounds produced are potential precursors for the biotechnological production of clinically important podophyllotoxin derivatives, and for investigation of the stereochemistry of the biosynthetic pathway.5�}7 The tert-butyldimethylsilylcyanohydrin 5 was synthesised in 3 steps from 3,4-dihydroxybenzaldehyde.Treatment of 5 with LDA followed by butenolide gave the adduct 6 in 80% yield as a 4:1 mixture of two diastereoisomers (Scheme 2). Treatment of the mixture with LDA followed by 4-tert- butyldimethylsilyloxy-3,5-dimethoxybenzaldehyde gave two products 4a (30%) and 4b (59%) which could be separated by column chromatography. Both 4a and 4b consisted of a mixture of two epimers which di€ered in their conRguration of the benzylic OH group.Cyclisation of 4a with TFA at 0 8C a€orded a single product 7a in 61% yield while cyclisation of 4b under the same conditions gave the C-4 epimer 7b in 58% yield, the structure of which was conRrmed by X-ray crystallography (Fig. 1). J. Chem. Research (S), 1998, 226�}227 J. Chem. Research (M), 1998, 1056�}1081 Scheme 1 Scheme 2 Fig. 1 X-Ray crystal structure of 7b (Ar a 4-tert-butyldimethylsilyloxy-3,5-dimethoxphenyl) *To receive any correspondence (e-mail: r.s.ward@swan.ac.uk). 226 J. CHEM. RESEARCH (S), 1998In a second series of experiments the tandem conjugate addition products 4a and 4b were treated with TBAF at 0 8C, with a view to regenerating the carbonyl group at C-6.In the event 4a or 4b gave the same fully desilylated compound 8 in 80¡À99% yield as a mixture of the two epimeric alcohols. In contrast, treatment of 4b with TBAF at ¡¦78 8C gave a mixture of two partially deprotected com- pounds 9 and 10, each as a mixture of epimeric alcohols.Further treatment of 9 with TBAF at 0 8C converted it into 8 (Scheme 3). Crystal data for 7b.DC42H67NO8Si3, Mr=798, F(000)= 864, triclinic, a= 7.183(4), b= 17.383(3), c =19.708(3) A �º , V=2409(2) A �º 3, = 81.52(1), = 83.34(4), = 84.21(4)8, space group P1, Z =2, Dx=1.101mg m¡¦3, l(Cu-K) = 1.54178 A �º . The X-ray data were collected using an Enraf- Nonius CAD-4 X-ray di€ractometer.Techniques used: 1H and 13C NMR, MS, IR, X-ray crystallography References: 13 Tables: 10 (1H and 13C NMR spectra of 4a, 4b, 6, 7a and 7b and X-ray data for 7b) Received, 23rd June 1997; Accepted, 20th January 1998 Paper E/7/04399F References cited in this synopsis 1 T. Ogiku, S. Yoshida, M. Takahashi, T. Kuroda, H. Ohmizu and T. Iwasaki, Tetrahedron Lett., 1992, 33, 4473, 4477. 2 T. Ogiku, S. Yoshida, T. Kuroda, M. Takahashi, H. Ohmizu and T. Iwasaki, Bull. Chem. Soc. Jpn, 1992, 65, 3495. 3 Y. Moritani, C. Fukushima, T. Ogiku, T. Ukita, T. Miyagishima and T. Iwasaki, Tetrahedron Lett., 1993, 34, 2787. 4 A. Pelter, R. S. Ward and N. P. Storer, Tetrahedron, 1994, 50, 10829. 5 J. P. Kutney, M. Arimoto, G. M. Hewitt, T. C. Jarvis and K. Sakata, Heterocycles, 1991, 32, 2305. 6 J. P. Kutney, Y. P. Chen, S. Gao, G. M. Hewitt, F. Furi-Brena, R. K. Milanova and N. M. Stoynov, Heterocycles, 1993, 36, 13. 7 J. P. Kutney, X. Du, R. Naidu, N. M. Stoynov and M. Takemoto, Heterocycles, 1996, 42, 479. Scheme 7a and 7b Scheme 3 J. CHEM. RESE
ISSN:0308-2342
DOI:10.1039/a704399f
出版商:RSC
年代:1998
数据来源: RSC
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20. |
A Concise and Convenient Method for the Synthesis of Pure Substituted Thioureas |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 5,
1997,
Page 228-229
K. Ramadas,
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摘要:
A Concise and Convenient Method for the Synthesis of Pure Substituted Thioureas K. Ramadas* and N. Janarthanan Centre for Agrochemical Research, SPIC Science Foundation, 110, Mount Road, Guindy, Madras 600 032, India Zinc dialkyldithiocarbamates offer excellent substrates for the pure thioureas required for antifungal and X-ray crystallographic studies. The synthetic methodology for variously substituted sym- metrical1 and unsymmetrical2 thioureas and guanidines3 has been well established in this laboratory and their biological activity is also well known.4 In pursuit of our interest in the study of the antifungal properties of thioureas, we required the products in a highly pure state.It may be noted that the end products were contaminated with sulfur which is un- desirable for antifungal studies since sulfur is well known to function as a fungicide. The removal of sulfur from the product poses problems in the isolation of the pure product. The approach presented herein makes use of dialkyldithio- carbamates, particularly the zinc salt, which as substrates provide a ready access to mixed thiocarbamides.The high- lights of the work include easy removal of the by-product zinc sulRde by Rltration, trapping of hydrogen sulRde by triethanolamine5 and excellent yield of the product in a pure form. The method involves the reaction of a zinc salt of dialkyldithiocarbamic acid with primary aliphatic or aromatic amine in the ratio of 1:2 in dimethylformamide at 65�}70 8C which led to the trisubstituted unsymmetrical thioureas (Scheme, Table A).In the above procedure (Scheme), if 4 equivalents of amine nucleophile were used instead of 2, both the dialkyl amine functionalities were displaced to yield 1,3- disubstituted symmetrical thioureas (Scheme, Table B). 1,3-Diaryl symmetrical thioureas containing deactivated arylamines, which are otherwise dicult to synthesise, were obtained in good yields. The reactions of zinc dialkyldithio- carbamate were extended to those with aliphatic diamines to provide cyclic thioureas (Scheme, Table C).Cava and co-workers18 studied the reactions of tetramethylthiuram disulRde (TMTD) with phenyllithium and showed the products to be a mixture of about equal amounts of the thioamide and the corresponding aryldithiocarbamate formed by competing nucleophilic attack at the thione carbon of the TMTD and the sulfur atom respectively. However, in our reactions the formation of the product is rationalised in terms of the formation of the intermediate isothiocyanate resulting from the nucleophilic attack on the thione carbon of zinc dialkyldithiocarbamate exclusively.To conclude then, this strategy involving the inexpensive zinc salts as ideal substrates for the synthesis of di€erently substituted thioureas works better than other methods available for this purpose.23 Techniques used: 1H NMR and elemental analysis References: 23 Schemes: 3 Tables A�}C: Reaction times, yield, mp and literature references for all thioureas J.Chem. Research (S), 1998, 228�}229 J. Chem. Research (M), 1998, 1101�}1108 Scheme Table A Synthesis of trisubstituted thioureas using zinc dialkyldithiocarbamates Product Reaction Yield Entry R R' time/h (%) 1 Me n-Butyl 2.0 76 2 Me Phenyl 2.0 86 3 Me o-Tolyl 2.0 88 4 Me m-NO2C6H4 2.5 86 5 Et Cyclohexyl 1.5 90 6 Et Phenyl 1.5 82 7 Et o-Tolyl 1.5 79 8 Et p-ClC6H4 2.5 75 Table B Synthesis of 1,3-disubstituted symmetrical thioureas using dialkyldithiocarbamates Product Reaction Yield Entry R R' time/h (%) 9 Me Phenyl 2.0 86 10 Me o-Tolyl 2.0 80 11 Me Cyclohexyl 2.0 88 12 Me n-Butyl 2.0 78 13 Me m-NO2C6H4 3.0 72 14 Me o-ClC6H4 2.5 76 15 Et Phenyl 2.0 84 16 Et o-Tolyl 2.0 82 17 Et m-NO2C6H4 3.0 71 Table C Synthesis of cyclic thioureas using zinc dialkyldithiocarbamates Product Reaction Yield Entry R X' time/min (%) 18 Me 2 30 76 19 Me 3 45 70 20 Et 2 45 80 21 Et 3 60 72 *To receive any correspondence (e-mail: ramadas@agro.smi.ernet.in). 228 J. CHEM. RESEARCH (S), 1998Received, 24th November 1997; Accepted, 14th January 1998 Paper E/7/08483H References cited in this synopsis 1 K. Ramadas, N. Janarthanan and S. Velmathi, Synth. Commun., 1997, 27, 2255. 2 K. Ramadas, N. Srinivasan and N. Janarthanan, Tetrahedron Lett., 1993, 34, 6447; K. Ramadas and N. Srinivasan, Synth. Commun., 1995, 25, 3381. 3 K. Ramadas and N. Srinivasan, Tetrahedron Lett., 1995, 36, 2841; K. Ramadas, N. Janarthanan and R. Pritha, Synth. Lett., 1997, 1053. 4 D. C. Schroeder, Chem. Rev., 1955, 55, 181. 5 K. Ramadas, Tetrahedron Lett., 1996, 37, 5161. (The success of the synthesis of thioureas depends upon the elimination of hydrogen sul®de from the reaction mixture. Triethanolamine forms a water soluble adduct with H2S which is liberated quanti- tatively by gentle warming of the acidi®ed solution to regenerate the tertiary amine.) 18 K.-Y. Jen and M. P. Cava, Tetrahedron Lett., 1982, 23, 2001. 23 G. Y. Sarkis and E. D. Faisal, J. Heterocycl. Chem., 1985, 22, 137; Houben, Methoden Org. Chem. (Houben-Weyl), 1983, VE4, 843; N. Yamazaki, T. Tomioki and F. Higashi, Synthesis, 1975, 384; A. R. Katritzky and M. F. Govdeer, J. Chem. Soc., Perkin Trans. 1, 1991, 2199 and all other methods cited therein. J. CHEM. RESEARCH (S),
ISSN:0308-2342
DOI:10.1039/a708483h
出版商:RSC
年代:1998
数据来源: RSC
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