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61. |
Synthesis of 4-Substituted Hexahydro-2(3H)-benzofuranones by Addition of Hydrides or Trimethylaluminium to 2-Ethoxycarbonylmethyl-cyclohexanones |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 8,
1997,
Page 482-483
Victor Oswaldo Nava-Salgado,
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摘要:
Synthesis of 4-Substituted Hexahydro-2(3H)- benzofuranones by Addition of Hydrides or Trimethylaluminium to 2-Ethoxycarbonylmethylcyclohexanones$ Victor Oswaldo Nava-Salgado and Marta Albores-Velasco* Departamento de Qu�Ê mica Orga�Ê nica, Facultad de Qu�Ê mica, Universidad Nacional Auto�Ê noma de Me�Ê xico, Circuito Interior Ciudad Universitaria, 04510 Me�Ê xico, D.F. The addition of complex hydride and trimethyl aluminium to 3-substituted and 3,3-disubstituted-2-carboxymethylcyclohexanones to produce cyclohexanols which could be cyclized to the corresponding benzofuranones was investigated; the stereochemistry of the addition was strongly influenced by the nature and size of the added nucleofiles and by the cyclohexanone-substituent.Hexahydro-2(3H)-benzofuranones constitute part of a number of biologically active natural products, including sesquiterpene lactones.1 Synthetic methods for these compounds are the focus of attention of many chemists.2 In the search for an alternative general method for the stereoselective synthesis of hexahydro-2(3H)-benzofurans, we present our results on the stereochemical course of the addition of hydrides and trimethylaluminium to and 3-R-3-vinyl-2-ethoxycarbonylmethylcyclohexanones (R a H or Me).Although the addition of hydrides or organometallic compounds to cyclohexanones has been widely studied,3 new methods are still sought.4 The hydride addition stereo- chemistry depends both on the size of the hydride and the cyclohexanone substituents,5 whereas the outcome of the addition of trimethylaluminium in hydrocarbon solvents depends on the substrate/organometallic reagent ratio.6 2-Ethoxycarbonylmethyl 3-R-3-vinylcyclohexanones (1, R a H) and (2, R a Me) were prepared by the addition of vinyl cuprate to cyclohex-2-en-1-one or to 3-methylcyclohex- 2-en-1-one and subsequent trapping the enolate with ethyl iodoacetate according to Andriamialisoa.7 The correspond- ing acid 3 was obtained in high yield by hydrolysis of a sample of the ketoester 2 with aqueous NaOH. The addition of hydrides and trimethylaluminium to cyclohexanones 1, 2 and 3 gave the corresponding alcohols 4�}8 (Scheme 1, Table 1).The cis alcohols cyclize spon- taneously to the cis-g-lactones under the reaction conditions, while trans alcohols only cyclize under acidic conditions (toluene-p-sulfonic acid). The well-established chemical shifts of the g-proton of hexahydro-(2H)-benzofuranones (ca. 4.5 ppm for the cis and 4.0 ppm for the trans fusion)8 were used to support the assignment of the cis and trans diastereoisomers. The cis�}lactones to trans-hydroxy esters ratios were determined from isolated products after column chromatography. The sodium tetrahydroborate reduction of the 3-vinyl- cyclohexanone 1 produced the corresponding axial and equatorial products 4 (Table 1, entry 1), in a 40:60 cis : trans ratio, the equatorial alcohol being the favoured product;3a,b whereas reduction of the 3-methyl-3-vinyl-cyclohexanone 2 gave the cis and trans cyclohexanols 5 in a 83:17 ratio, (Table 1, entry 2), the result of the stronger bulk e€ect of the substituents.3c�}e In contrast to the last result, the lithium aluminium hydride reduction of the 3-methyl-3- vinyl-keto-acid 3 a€orded the cis, and trans hydroxy-acids 6 in a 40 :60 ratio (Table 1, entry 3).The electronic e€ect produced by the hydride complexation with the acid group and the subsequent hydride transfer from the same side of the acid substituent9 might explain this result.The cis-6 hydroxy-acid also cyclizes to the cis-11 lactone, while the trans-6 hydroxy-acid was isolated, esteriRed with diazomethane and cyclized by acid catalysis to the trans-11 lactone. The reaction of trimethylaluminium with the ketoesters 1 and 2 and with the keto-acid 3 gave exclusively cis (axial) alcohols 7, 8, and 9, which cyclize spontaneously to the respective cis lactones 12 and 13 (Table 1, entries 4�}6).Apparently, the steric e€ect of the nucleophile and/or the 2- and 3-substituents determines the course of the addition by the equatorial side of the molecule, in spite of previous reports of trimethyl aluminium transfer of methyl group by the axial side of cyclohexanones.6 In summary, the addition of the trimethylaluminium to 2-ethoxycarbonylcyclohexanones leading to the corre- sponding cis alcohols, which cyclize spontaneously to the cis-g-lactones, constitutes an alternative stereoselective synthesis for 4-substituted cis-hexahydro-2(3H)-benzo- furanones.By addition of hydrides, mixtures are obtained, depending on the cyclohexanone substituents. The trans alcohols can be cyclized by re�Puxing in benzene with acid catalysis to give the corresponding trans benzofuranones. J. Chem. Research (S), 1998, 482�}483$ Scheme 1 $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 482 J. CHEM. RESEARCH (S), 1998Experimental Reduction of Ketoester 1 with NaBH4.DA solution of 1 (700 mg, 3.30 mmol) in 20 ml ethanol was stirred with (42.0 mg, 1.11 mmol) sodium tetrahydroborate at room temperature. After 4 h, the reac- tion was quenched with solid NH4Cl, the ethanol was evaporated and the solid residue was extracted with diethyl ether.After column chromatography [silica gel; hexane/AcOEt (9 :1)], 190 mg of cis-10 and 354 mg of trans-4 (40:60) was obtained. Total yield: 84%. cis-10 Colourless oil; /cm¡¦1=1778 (C1O); H (90 MHz, CDCl3) 1.00¡À2.80 (m, 10 H), 4.57 (q, J 3.5 Hz, 1 H), 4.85¡À5.10 (m, 2 H), 5.45 (ddd, J 6.5, 7.9 and 18.0 Hz, 1 H); m/z (EI) 166 (M�¢, 75%), 67 (100). trans-4: Colourless oil; /cm¡¦1 3450 (OH), 1730 (C1O); H (90 MHz, CDCl3) 1.00¡À2.60 (m, 14 H), 3.30 (dt, J 5.0 and 10.1 Hz, 1 H), 4.01 (q, J 7.1 Hz, 2 H), 4.90¡À5.15 (m, 2 H), 5.60 (ddd, J 6.5, 7.9 and 18.0 Hz, 1 H); m/z (EI) 212 (M�¢, 3%), 67 (100).Reduction of Ketoester 2 with NaBH4.DUsing the previous method, cis-11 and trans-5 were obtained. cis-11: Colourless oil; /cm¡¦1 1780 (C1O); H (90 MHz, CDCl3) 0.99 (s, 3 H), 1.00¡À2.70 (m, 9 H), 4.60 (m, 1 H), 5.00¡À5.20 (m, 2 H), 5.8 (dd, J 12.0 and 18.0 Hz, 1 H). m/z (EI) 180 (M�¢, 36%), 81 (100). trans-5: Colourless oil; /cm_1 3450 (OH), 1740 (C1O); H (90 MHz, CDCl3) 0.87 (s, 3 H), 0.98¡À2.30 (m, 13 H), 3.40 (dt, J 5.0 and 10.2 Hz, 1 H), 4.00 (q, J 7.1 Hz, 2 H), 4.80¡À5.10 (m, 2 H), 5.60 (dd, J 10.2 and 17.3 Hz, 1 H).trans-Hexahydro-4-vinyl-2(3H)benzofuranone 10.DA mixture of trans-4 (200 mg, 0.94 mmol) and toluene-p-sulfonic acid (ca. 5mg) was boiled under re¡¥ux in 20 ml benzene for 2 h. After cooling to room temperature, the product was extracted with 30 ml of diethyl ether. Column chromatography [silica gel; hexane/AcOEt (9 :1)] produced 131 mg (84%) of trans-10 as colourless oil./cm_1 1780 (C1O); H (90 MHz, CDCl3) 1.00¡À2.60 (m, 10 H), 3.95 (dt, J 4.0 and 10.0 Hz, 1 H), 5.00¡À5.30 (m, 2 H), 5.8 (ddd, J 6.5, 7.9 and 18.0 Hz, 1 H); m/z (EI) 166 (M�¢, 69%), 67 (100). trans-Hexahydro-4-methyl-4-vinyl-2(3H)benzofuranone 11.DUsing the previous method, trans-11 was obtained as colourless oil. /cm¡¦1 1775 (C1O); H (90 MHz, CDCl3) 1.00 (s, 3 H), 1.20¡À2.60 (m, 10 H), 4.05 (m, 1 H), 4.85¡À5.30 (m, 2 H), 5.60 (dd, J 12.0 and 18.0 Hz, 1 H).m/z (EI) 180 (M�¢, 52%), 81 (100). Addition of Al(CH3)3 to Ketoester 1.Dcis-Hexahydro-7a-methyl-4- vinyl-2(3H)benzofuranone 12. To a solution of 1 (1.00 g, 4.76 mmol) in 20 ml benzene was added 4Al(CH3)33Et2O10 (1.37 g, 4.75 mmol) at room temperature. After the addition, the reaction mixture was heated at 50 8C for 3 days. The reaction was allowed to cool to room temperature, diluted with 50 ml diethyl ether and quenched by addition of 30 ml water.The NaCl saturated aqueous phase was extracted with diethyl ether (350 ml). After column chromatog- raphy of the organic (95: 5)], 7.20 mg (84%) of cis-12 was obtained as colourless oil. /cm¡¦1 1770 (C1O); H (90 MHz, CDCl3, TMS) 1.10¡À2.50 (m, 13 H), 4.90¡À5.10 (m, 2 H), 5.45 (ddd, J 6.5, 7.9 and 18.0 Hz, 1 H); m/z (EI) 180 (M�¢, 23%), 165 (100). cis-Hexahydro-4,7a-dimethyl-4-vinyl-2(3H)benzofuranone 13.DUsing the previous method, cis-13 was obtained as colourless oil./cm¡¦1 1780 (C1O); H (90 MHz, DCCl3) 0.85 (s, 3 H), 1.05¡À2.40 (m, 12 H), 4.65¡À5.00 (m, 2 H), 5.60 (dd, J 12.0 and 18.0 Hz, 1 H). m/z (EI) 194 (M�¢, 45%), 81 (100%). Received, 24th December 1998; Accepted, 8th April 1998 Paper E/7/09279B References 1 (a) M. A. Battiste, L. Strekowski, D. P. Varderbilt, M. Visnick, R. W. King and J. L. Nation, Tetrahedron Lett., 1983, 24, 2611; (b) C. H.Chen, L. M. Yang, T. T. Y. Lee, Y. C. Shen, D. C. Zhang, D. J. Pan, A. T. MacPhail, D. R. MacPhail and S. Y. Liu, Bioorg. Med. Chem., 1994, 2, 137; (c) R. J. Marles, L. Pazos-Sanou, C. M. Compadre, J. M. Pezzuto, E. Bloszyk and J. T. Arnason, Recent Adv. Phytochem., 1995, 29, 336; (d) O. S. Giordano, M. J. Pestchanker, E. Guerreiro, J. R. Saad, R. D. Enriz, A. M. Rodriguez, E. A. Jauregui, J. Guzman, A. O. M. Maria and G. H. Wendel, J. Med. Chem., 1992, 35, 2452. 2 (a) A. Masayoshi, Yuki Gosei Kagaku Kyokaishi 1992, 50, 858; (b) A. K.Banerjee, W. J. Vera and N. C. Gonzalez, Tetrahedron, 1993, 49, 4761; (c) P. T. Lansbury and J. J. La Clair, Tetrahedron Lett., 1993, 34, 4431. 3 (a) H. Handel and J. L. Pierre, Tetrahedron Lett., 1976, 24, 2029; (b) A. L. Gemal and J. L. Luche, J. Am. Chem. Soc., 1981, 103, 5454; (c) J. Ficini and A. Maujenn, Bull. Soc. Chem. Fr., 1971, 219; (d) H. Felkin and C. Frajerman, Tetrahedron Lett., 1971, 383; (e) J. R. Luderer, J.E. Wodall and J. L. Pyle, J. Org. Chem., 1971, 36, 2909; ( f ) J. T. Laemmie, E. C. Ashby and P. V. Roling, J. Org. Chem., 1973, 38, 2526. 4 (a) M. C. Barden and J. Schwartz, J. Org. Chem., 1995, 60, 5963; (b) Y. Yamamoto, H. Kin, I. Suzuki and N. Asao, Tetrahedron Lett., 1996, 37, 1963; (c) C. W. Lindsley and M. DiMare, Tetrahedron Lett., 1994, 35, 5141; (d) G. A. Molander, Chem. Rev., 1992, 92, 29; (e) R. Adam, C. Villiers, M. Ephritikhine, M. Lance, M. Nierlich and J. Vigner, New J. Chem., 1993, 17, 455. 5 (a) E. L. Eliel and Y. Senda, Tetrahedron, 1970, 2411; (b) J. C. Richer, J. Org. Chem., 1965, 30, 324; (c) J. A. Marshall and P. O. Carroll, J. Org. Chem., 1965, 30, 2748. 6 (a) E. C. Ashby, S. H. J. Yu and P. V. Roling, J. Org. Chem., 1972, 37, 1918; (b) E. C. Ashby and J. T. Laemmie, Chem. Rev., 1975, 75, 521. 7 R. Z. Andriamialisoa, M. Fetizon and I. Hanna, Tetrahedron, 1984, 40, 4285. 8 (a) W. Herz and L. A. Glick, J. Org. Chem., 1973, 28, 2970; (b) P. A. Greico, T. Oguri, C. J. Wang and E. Williams, J. Org. Chem., 1977, 42, 4113. 9 M. Akhtar and S. Marsh, J. Chem. Soc. (C), 1966, 937. 10 D. T. Hurd, J. Org. Chem., 1948, 13, 711. Table 1 Nucleophilic additions to substituted cyclohexanones 1, 2 and 3 Product Entry Substratea Nucleophile Alcohol Lactone Yieldb (%) Ratioc (cis:trans) 1 1 NaBH4 4 10 84 40:60 2 2 NaBH4 5 11 68 83:17 3 3 LiAlH4 6 11 45 40:60 4 1 Al(CH3)3 d 7 12 84 100:0 5 2 Al(CH3)3 d 8 13 56 100:0 6 3 Al(CH3)3 d 9 13 76 100:0 aStructures in Scheme 1. bIsolated material after column chromatography. ccis Lactones:trans hydroxyesters. dUsed as etherate [4Al(CH3)33OEt2]. J. CHEM. RESEARCH (S), 1998
ISSN:0308-2342
DOI:10.1039/a709279b
出版商:RSC
年代:1998
数据来源: RSC
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62. |
A Convenient Synthesis of 2-Aryl Derivatives of 4a,5,6,7,8,8a-Hexahydrospiro[4H-1,3-benzoxazine-4,1′-cyclohexane] |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 8,
1997,
Page 484-485
Axel Couture,
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摘要:
A Convenient Synthesis of 2-Aryl Derivatives of 4a,5,6,7,8,8a-Hexahydrospiro[4H-1,3-benzoxazine- 4,1'-cyclohexane]$ Axel Couture,* Eric Deniau, Pierre Grandclaudon and Mihai Vata Laboratoire de Chimie Organique Physique, Associe�Ê au CNRS (URA n8 351), Universite�Ê des Sciences et Technologies de Lille I, F-59655 Villeneuve d'Ascq Cedex, France Various 2-aryl derivatives of 4a,5,6,7,8,8a-hexahydrospiro[4H-1,3-benzoxazine-4,1'-cyclohexane] have been efficiently prepared by the acid-catalysed reaction of 2-(1-cyclohexen-1-yl)cyclohexanol with aromatic carbonitriles. 5,6-Dihydro-4H-1,3-oxazines are a class of six-membered heterocyclic compounds that have found use in a wide variety of procedures. Thus, they are useful in the synthesis of surfactants1 and liquid crystals2 and have been used for cationic ring-opening polymerizations.3,4 The oxazine ring system can be regarded as a masked carbonyl moiety5 and chiral oxazines are valuable synthons for certain asymmetric syntheses.6 In addition, derivatives of these ring systems have displayed various useful pharmacological activities. For example, they have been shown to be hydrocarbon anti- oxidants7 and choline acetyl transferase inhibitors.8 However, the construction of architecturally sophisticated compounds with a spiro carbon centre embedded in their skeleton is particularly demanding and their elaboration still remains a synthetically challenging task.9,10 We report here a convenient and ecient synthesis of the previously unattainable cis- and trans-2-aryl-hexahydrobenzoxazines possessing a spiro heterocyclic framework.Several synthetic routes to partly or fully substituted 5,6-dihydro-4H-1,3-oxazines have been reported, includ- ing (a) the reaction of 2,4-diols,11 1,3-dioxanes12 and unsaturated alcohols13 with carbonitriles, (b) the photo- induced ring closure of aromatic dienamides14 and (c) the heterocyclization of N-(g-halogenoalkyl)amides with potass- ium �Puoride on alumina.15 However, the most ecient route relies upon the amidoalkylation of oleRns.16a Some of these methods allow the formation of 4,4-disubstituted model compounds but are mainly conRned to the synthesis of monocyclic 5,6-dihydro-4H-1,3-oxazines. Several synthetic strategies have been developed for the elaboration of cycloalkyl-fused bicyclic oxazines, namely by intramolecular [4 a 2] cycloaddition of N-acyliminium compounds with alkene dienophiles16 but these methods are rather limited in scope and do not permit the incorporation of a spiro carbon centre.Our strategy hinges upon the acid-catalysed reaction of cis- and trans-2-(1-cyclohexen-1-yl)cyclohexanol (2) with the aromatic carbonitriles 3a�}f and allows the synchronous formation of the hexahydrobenzoxazine framework13 and the creation of the spiro carbon centre (Scheme 1). Initially the bicyclic g,d-unsaturated alcohol 2 was easily obtained as a mixture of cis and trans isomers (60 : 40)17 by reduction of the parent 2-(1-cyclohexen-1-yl)cyclohexanone 1, a pro- duct of the aldol dimerization of cyclohexanone.18 After numerous attempts we found that completion of the annula- tion reaction was best achieved as a one-pot reaction by slow and dropwise sequential addition of the suitable carbo- nitriles 3a�}f followed by the alcohol 2 in ice-cooled sulfuric acid.The results of a representative series of products obtained by this method are presented in Table 1.The cis and trans stereochemistry of the fused compounds 4a�}f obtained has been assigned from the chemical shift of the proton vicinal to the oxygen atom (e.g. cis-4a, d a 4.51 ppm; trans-4a, d a 3.97 ppm). Detailed analysis by NMR spectroscopy on related systems19 has clearly established that the 8a-H chemical shifts of the cis isomers are invari- ably increased by 0.50�}0.60 ppm compared with their trans counterparts. Moreover the spiro structure of 4a�}f was con- Rrmed mainly by 75 MHz 13C NMR spectroscopy, which clearly indicates the presence of three (4a,e,f ) or four (4b�}d) non-protonated carbon centres in the spiro annulated com- pounds 4. In particular the non-protonated character of the carbon nucleus a to the nitrogen atom (e.g.d 53.3 ppm for trans-4a) was unambiguously established by comparison of (DEPT) spectra with di€erent pulse angles y. From a mechanistic point of view we can assume that the formation of the annulated products 4a�}f proceeds via the intermediacy of the protonated imidate 5 obtained after preliminary protonation of the carbonitrile 3 and nucleo- philic attack of the unsaturated alcohol 2.Subsequent addition on the protonated cycloalkenyl moiety ensures completion of the spiroannulation reaction. It is noteworthy that the use of a g,d-unsaturated alcohol is a prerequisite to the spiroannulation process since all attempts to perform J. Chem. Research (S), 1998, 484�}485$ Scheme 1 Reagents and conditions: i, LiAlH4, THF, reflux 3 h; ii, H2SO4 (96%), 0 8C, then 3a�}f, then 2, 0 8C, 10 h $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 484 J. CHEM. RESEARCH (S), 1998the same reaction with the isomeric allylic alcohol 620 were unrewarding. Experimental General Procedure for the Preparation of 2-Aryl-4a,5,6,7,8,8a- hexahydrospiro[4H-1,3-benzoxazine-4,1'-cyclohexanes] 4a�}f.DTo ice- cooled sulfuric acid (96%, 7 mL) was added the appropriate carbo- nitrile 3a�}f (6 mmol) by syringe over a period of 15 min.The mixture was then stirred under Ar for 5 min and the alcohol 3 (1 g, 5.5 mmol) was then slowly added to the sulfuric acid solution. The reaction mixture was stirred at 0 8C for an additional 10 h and the resulting solution was slowly and carefully transferred into a 100 mL beaker containing a vigorously stirred CH2Cl2�}ice mixture (30 mL/30 g).After the addition was complete, concentrated aqueous KOH (30%), previously cooled in ice, was then carefully added until the solution was neutralized. The organic layer was separated and the aqueous phase was extracted twice with CH2Cl2 (220 mL). The combined organic extracts were washed with water and dried (MgSO4). Removal of the solvent under vacuum a€orded a residual viscous liquid which was puriRed by column chromatog- raphy on silica gel using AcOEt�}hexane (5:95) as eluent.The trans isomers of compounds 4 were invariably eluted Rrst in all cases. Received, 30th January 1998; Accepted, 3rd April 1998 Paper F/8/02696C References 1 T. Saegusa, M. Miyamoto and Y. Sano, Eur. Pat. 244 828, 1987 (Chem. Abstr., 1988, 108, 151211). 2 A. Waechler and B. Scheuble, Ger. Pat., 3 601 221, 1986 (Chem. Abstr., 1987, 106, 25896). 3 P. Le Perchec, R.SalleA and B. Sillion, Revue de l'Institut Franc�� ais du PeAtrole, 1986, 41, 275. 4 S. Koyabayashi and T. Saegusa, in Ring Opening Polymer- ization, ed. K. J. Ivin and T. Saegusa, Elsevier, New York, 1981, vol. 2, p. 761. 5 T. W. Greene, Protective Groups in Organic Synthesis, Wiley, New York, 1991, p. 265. 6 A. I. Meyers and M. Shipman, J. Org. Chem. 1991, 56, 7098. 7 P. R. Parlman and L. D. Burns, US Pat., 4 313 738, 1980 (Chem. Abstr., 1982, 96, 126041). 8 N. B.Mekta, D. L. Musso and H. L. White, Eur. J. Med. Chem. (Chim. Ther.), 1985, 20, 443. 9 S. F. Martin, Tetrahedron, 1980, 36, 419. 10 (a) A. P. Krapcho, Synthesis, 1976, 425; (b) B. M. Trost and B. R. Adams, J. Am. Chem. Soc., 1983, 105, 4849. 11 (a) E. J. Tillmanns and J. J. Ritter, J. Org. Chem., 1957, 22, 839; (b) A. A. Gevorkyan, G. G. Tokmadzhyan and L. A. Saakyan, Arm. Khim. Zh. 1977, 30, 693 (Chem. Abstr., 1978, 88, 170053). 12 (a) A. A. Gevorkyan, G. G. Tokmadzhyan and L.A. Saakyan, Arm. Khim. Zh., 1977, 30, 748 (Chem. Abstr., 1978, 88, 152510); (b) A. A. Gevorkyan and G. G. Tokmadzhyan, Arm. Khim. Zh., 1977, 30, 2696 (Chem. Abstr., 1977, 87, 68260). 13 A. A. Gevorkyan and G. G. Tokmadzhyan, USSR Pat., 649 713, 1979 (Chem. Abstr., 1979, 90, 204113). 14 C. Bochu, A. Couture, P. Grandclaudon and A. Lablache- Combier, J. Chem. Soc., Chem. Commun., 1986, 839. 15 M. A. Mitchell and B. C. B(a) A. R. Katritzky, I. V.Shcherbakova, R. D. Tack and Xue- Qian Dai, Tetrahedron, 1993, 49, 3907 and refs cited therein; (b) P. M. Scola and S. M. Weinreb, J. Org. Chem., 1986, 51, 3248. 17 T. W. Bell, J. R. Vargas and G. Crispino, J. Org. Chem., 1989, 54, 1978. 18 C. Bochu, A. Couture and P. Grandclaudon, J. Org. Chem., 1988, 53, 4852. 19 (a) G. Bernath, F. Fulop, L. Gera, L. Hackler, A. Kalman, Gy. Argay and P. Sohar, Tetrahedron, 1979, 35, 799; (b) A. R. Katritzky, I. V. Shcherbakova, R. D.Tack and B. Mancheno, Magn. Reson. Chem., 1993, 31, 615. 20 J. Saltiel and G. R. Marchand, J. Am. Chem. Soc., 1991, 113, 2702. Table 1 Selected data for 2-aryl-4a,5,6,7,8,8a-hexahydrospiro[4H-1,3-benzoxazine-4,1'-cyclohexanes] 4a�}f Found (calc.) (%) Compound Ar Yielda (%) Mp (T/ 8C) dH b (ppm) dC (ppm) C H N 4a C6H5 65 trans 117�}118 1.10�}1.70 (13 H, m), 1.77�} 1.85 (4 H, m), 2.17�}2.31 (2 H, m), 3.97 (1 H, dt, J 10.5, 4.5), 7.30�}7.37 (3 H, m), 7.98�}8.00 (2 H, m) C, 53.3, 135.0, 150.4; CH, 47.9, 73.0, 127.1, 127.8, 129.7; CH2, 21.3, 21.5, 24.4, 25.3, 26.3, 27.0, 33.0, 34.6, 36.6 80.4 (80.5) 8.9 (8.9) 5.0 (4.9) cis 79�}80 1.04�}1.85 (18 H, m), 2.19 (1 H, dt, J 10.4, 4.5), 4.51 (1 H, s), 7.31�}7.41 (3 H, m), 7.93�}7.99 (2 H, m) C, 54.9, 134.6, 152.4; CH, 37.6, 69.3, 127.1, 127.8, 129.3; CH2, 19.9, 21.2, 21.8, 21.9, 25.4, 26.1, 31.1, 35.7, 39.1 4b 4-MeC6H4 63 trans 90�}91 80.8 (80.8) 9.0 (9.15) 4.7 (4.7) cis 80�}81 4c 4-ClC6H4 66 trans 104�}105 72.1 (71.8) 7.5 (7.6) 4.2 (4.4) cis 81�}82 4d 4-MeOC6H4 62 trans 93�}94 76.5 (76.6) 8.7 (8.8) 4.5 (4.6) cis 79�}80 4e 2-Thienyl 50 trans 91�}92 1.05�}1.90 (13 H, m), 1.70�} 1.86 (4 H, m), 2.14�}2.28 (2 H, m), 3.96 (1 H, dt, J 10.5, 4.4), 6.98 (1 H, dd, J 5.0, 3.6), 7.27 (1 H, dd, J 5.0, 1.25), 7.45 (1 H, dd, J 3.6, 1.25) C, 53.5, 139.7, 147.3; CH, 48.0, 73.3, 126.8, 126.9, 127.7; CH2, 21.2, 21.4, 24.3, 25.3, 26.2, 27.0, 32.9, 34.5, 36.5 70.8 (70.55) 8.0 (8.0) 4.85 (4.8) cis 102�}103 1.01�}1.88 (18 H, m), 2.13�} 2.17 (1 H, m), 4.50 (1 H, s), 6.99 (1 H, dd, J 5.0, 3.6), 7.29 (1 H, dd, J 5.0, 1.25), 7.50 (1 H, dd, J 3.6, 1.25) C, 55.1, 138.9, 149.2; CH, 37.6, 69.7, 127.0, 127.1, 127.6; CH2, 19.8, 21.2, 21.7, 21.9, 25.4, 26.0, 31.0, 35.5, 38.9 4f 2-Furyl 42 trans 79�}80 75.0 (74.8) 8.5 (8.6) 5.0 (5.1) cis 91�}92 aYields determined for the mixture (trans a cis) before chromatographic separat
ISSN:0308-2342
DOI:10.1039/a802696c
出版商:RSC
年代:1998
数据来源: RSC
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63. |
The Aza-ene Reaction of Heterocyclic Ketene Aminals with 4-Phenyl-1,2,4-triazoline-3,5-dione |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 8,
1997,
Page 486-487
Jian-Heng Zhang,
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摘要:
The Aza-ene Reaction of Heterocyclic Ketene Aminals with 4-Phenyl-1,2,4-triazoline-3,5-dione$ Jian-Heng Zhang, Mei-Xiang Wang and Zhi-Tang Huang* Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100080, China Heterocyclic ketene aminals bearing a secondary enamine moiety underwent an efficient aza-ene reaction with 4-phenyl- 1,2,4-triazoline-3,5-dione under very mild conditions, while no reaction was observed with their tertiary enamine analogues. The ene reaction has received much attention for a number of decades because of its synthetic potential and its interest- ing mechanistic aspects in organic chemistry.1 While the ene reactions of an ole¢çn bearing an allylic hydrogen atom (the `carba-ene') with activated alkenes and alkynes (the `carba-enophiles') and with heteroenophiles, including carbonyl, thiocarbonyl compounds, imines, nitroso and azo compounds, are well documented,1 little is known of the ene reactions involving hetero-ene components.2¡¾4 This is particularly true for those of hetero-ene systems contain- ing a heteroatom at the 2-position (X a heteroatom) (Scheme 1).2,3 Nevertheless, we envisaged that hetero-ene reactions of secondary enamines would provide novel and valuable synthetic routes to imines 3 and to ketones, amines and N-heterocycles, respectively, upon the hydrolysis, reduction and cyclization of 3.Heterocyclic ketene aminals, also known as cyclic 1,1-ene- diamines, are powerful and versatile synthons for various types of compounds that are di.cult to obtain by other synthetic methods.5 Most noticeably, however, heterocyclic ketene aminals bearing a secondary amino group have been shown recently to be a unique aza-ene component, and the aza-ene reaction proceeded readily when ethyl propiolate was used as an enophile.6 To examine the scope and limi- tations of this novel aza-ene component in organic synthesis, we have extended the aza-ene reactions of heterocyclic ketene aminals utilizing a range of carba- and heteroeno- philes.Herein we report the reaction of aroyl-substituted heterocyclic ketene aminals with 4-phenyl-1,2,4-triazoline- 3,5-dione (9, PTAD). The reaction of imidazolidine-containing heterocyclic ketene aminals 4 and 5 with 9 was rapid and e.cient at room temperature and the corresponding adducts (12) were obtained immediately and the products 13 were formed within one hour. Signi¢çcantly, when 1,3-dimethyl-2-aroyl- methyleneimidazolidine 6 was employed, no reaction was observed and the starting materials were recovered.It should be noted that the only di€erence in structure between 4 or 5 and 6 is that the former has at least one secondary amino group, being a secondary enamine species, while the latter is a tertiary enamine compound. These results suggest that the addition of heterocyclic ketene aminals to PTAD does not proceed through a Michael addition mechanism, or through a [2 a 2] cycloaddition followed by rearrangement pathway.6 In other words, a secondary enamine is a reactive component and therefore the aza-ene reaction is most likely involved (Scheme 2).Surprisingly, the reaction of six-membered heterocyclic ketene aminals 7 with 9 under the same conditions did not yield the desired aza-ene adducts. Instead, benzoylphenyl- urea (PhCONHCONHPh) 15 was isolated as the sole pro- duct. Only when the reaction temperature was lowered to ¢§60 8C, using dichloromethane (DCM) as solvent, was the aza-ene reaction e€ected e.ciently.Aza-ene adduct 14 was found to decompose readily at room temperature when treated with ethanol and other solvents, resulting in the formation of 15. The instability of aza-ene products from 1-methylpyrimidine-substituted heterocyclic ketene aminals 8 inhibited their successful isolation, though the initial formation of the aza-ene adducts was evident by thin-layer chromatography. The reason for the fragmentation of 14 into 15 is not clear. From the above ¢çndings it can be concluded that hetero- cyclic ketene aminals are e€ective aza-ene components.The aza-ene reaction between them and the hetero-enophile J. Chem. Research (S), 1998, 486¡¾487$ Scheme 1 Scheme 2 $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 486 J. CHEM. RESEARCH (S), 1998PTAD takes place easily under very mild thermal con- ditions. Experimental For general experimental details see our previous paper.6 General Procedure for the Synthesis of 12 and 13.�¢To the solution of heterocyclic ketene aminals 4 or 5 (1.0 mmol) in 1,4- dioxane (20 cm3) was added dropwise a solution of 4-phenyl-1,2,4- triazoline-3,5-dione (9)7 (1.0 mmol) in 1,4-dioxane (5 cm3) at room temperature. Product 12 precipitated immediately after the addition of 3 while 13 was formed after another 0.5¡¾1 h.Recrystallization from the appropriate solvent gave pure 12 and 13. 12a. Yield: 75%, mp 203¡¾205 8C (white solid from ethanol); (Found: C, 63.0; H, 4.6; N, 19.2. C19H17N5O3 requires C, 62.80; H, 4.72; N, 19.28%); max/cm¢§1 3430, 3300, 1740 and 1675; lmax/nm (log e in ethanol) 226 (4.21) and 292 (4.04). dH [200 MHz, (CD3)2SO] 10.95 (s, 1 H), 9.05 (s, 1 H), 8.00 (s, 1 H), 7.50¡¾7.15 (m, 10 H), 3.75 (t, 2 H) and 3.55 (t, 2 H); dC [50 MHz, (CD3)2SO] 186.4, 163.6, 150.2, 149.6, 141.5, 132.3, 128.4, 128.3, 127.3, 127.1, 126.0, 125.9, 88.1, 44.2 and 41.8; m/z (FAB) 363 (Ma); m/z (EI) 303 (4%), 201 (24), 180 (53), 105 (54) and 44 (100). 12b.Yield: 65%, mp 205¡¾207 8C (white solid from ethanol); (Found: C, 63.5; H, 5.0; N, 18.9. C20H19N5O3 requires C, 63.65; H, 5.07; N, 18.56%); max/cm¢§1 3420, 3280, 1740 and 1675; lmax/nm (log e in ethanol) 228 (4.22) and 296 (4.11); dH 10.95 (s, 1 H), 9.10 (s, 1 H), 7.90 (s, 1 H), 7.43 (d, 2 H), 7.12 (d, 2 H), 7.40¡¾7.20 (m, 5 H), 3.65 (t, 2 H), 3.62 (t, 2 H), 2.30 (s, 3 H); dC 186.3, 163.7, 150.4, 149.5, 138.7, 138.1, 132.3, 128.6, 128.1, 127.4, 126.1, 126.0, 88.1, 44.3, 41.9 and 20.9; m/z (EI) 377 (Ma, 2%), 317 (27), 258 (6), 215 (19), 194 (92) and 119 (100). 12c. Yield: 70%, mp 187¡¾189 8C (white solid from ethanol); (Found: C, 60.4; H, 4.97; N, 17.7. C20H19N5O4 requires C, 61.06; H, 4.87; N, 17.80%); max/cm¢§1 3400, 3300, 1745 and 1670; lmax/nm (log e in ethanol) 225 (sh) and 302 (4.13); dH 10.95 (s, 1 H), 9.10 (s, 1 H), 7.88 (s, 1 H), 7.43 (d, 2 H), 7.40¡¾7.25 (m, 5 H), 6.86 (d, 2 H), 3.75 (s, 3 H), 3.70 (t, 2 H) and 3.55 (t, 2 H); dC 185.6, 163.8, 159.7, 150.4, 149.7, 133.7, 132.3, 128.5, 127.9, 127.3, 126.1, 112.8, 87.9, 55.1, 44.3 and 41.9; m/z (EI) 393 (Ma, 2%), 333 (13), 231 (10), 210 (43) and 135 (100). 12d. Yield: 80.5%, mp 208¡¾210 8C (white solid from ethanol); (Found: C, 57.3; H, 4.3; N, 17.2.C19H16ClN5O3 requires C, 57.36; H, 4.05; N, 17.61%); max/cm¢§1 3400, 3300, 1745 and 1670; lmax/nm (log e in ethanol) 228 (4.30) and 296 (4.20); dH 10.95 (s, 1 H), 9.02 (s, 1 H), 8.02 (s, 1 H), 7.42 (d, 2 H), 7.40¡¾7.30 (m, 5 H), 7.24 (d, 2 H), 3.75 (t, 2 H), 3.55 (t, 2 H); dC 185.0, 163.6, 150.5, 149.8, 140.4, 133.4, 132.3, 128.7, 128.0, 127.7, 127.4, 126.1, 88.2, 44.4 and 41.9; m/z (FAB) 398 (M a 1)a; m/z (EI) 337 (6%), 235 (20), 214 (30) and 139 (100). 13a. Yield: 53%, mp 162¡¾164 8C (colourless needles from ethanol); (Found C, 63.8; H, 5.1; N, 18.4. C20H19N5O3 requires C, 63.65; H, 5.07; N, 18.56%); max/cm¢§1 3410, 3210, 1740 and 1680; lmax/nm (log e in ethanol) 226 (4.19) and 294 (4.16); dH 11.25 (s, 1 H), 9.65 (s, 1 H), 7.45¡¾7.08 (m, 10 H), 3.65 (s, 4 H), 2.95 (s, 3 H); dC 188.9, 161.7, 150.2, 149.3, 141.8, 131.8, 128.5, 128.1, 127.5, 127.2, 126.0, 125.6, 88.0, 51.7, 41.5 and 33.2; m/z (EI) 377 (Ma, 6%), 293 (11), 229 (20), 180 (32) and 119 (100). 13b. Yield: 68%, mp 169¡¾171 8C (colourless needles from ethyl acetate/light petroleum, bp 60¡¾90 8C); (Found: C, 64.3; H, 5.4; N, .3. C21H21N5O3 requires C, 64.43; H, 5.41; N, 17.89%); max/cm¢§1 3410, 3200, 1745 and 1690; lmax/nm (log e in ethanol) 228 (4.17) and 296 (4.16); dH 11.30 (s, 1 H), 9.85 (s, 1 H), 7.40 (d, 2 H), 7.38¡¾7.16 (m, 5 H), 7.14 (d, 2 H), 3.63 (t, 2 H) 3.58 (t, 2 H), 2.95 (s, 3 H), 2.35 (s, 3 H); dC 190.6, 162.4, 151.1, 151.0, 138.7, 138.1, 131.5, 128.9, 128.4, 127.9, 126.0, 125.8, 89.1, 52.1, 41.5, 33.6 and 21.2; m/z (EI) 391 (Ma, 2%), 307 (11), 229 (24), 194 (34) and 119 (100). 13c. Yield: 70%, mp 120¡¾122 8C (colourless needles from light petroleum, bp 60¡¾90 8C/1,4-dioxane) (Found: C, 61.7; H, 5.5; N, 17.1. C21H21N5O4 requires C, 61.90; H, 5.20; N, 17.19%); max/cm¢§1 3400, 3220, 1740 and 1685; lmax/nm (log e in ethanol) 225 (sh) and 300 (4.20); dH 11.15 (s, br, 1 H), 9.75 (s, 1 H), 7.42 (d, 2 H), 7.45¡¾7.10 (m, 5 H), 6.88 (d, 2 H), 3.75 (s, 3 H), 3.60 (s, 4 H), 2.95 (s, 3 H); dC 188.3, 161.9, 159.5, 150.3, 149.5, 134.1, 131.9, 128.7, 128.3, 127.5, 126.2, 112.8, 88.0, 55.1, 51.9, 41.6 and 33.4; m/z (EI) 407 (Ma, 2%), 323 (11), 229 (14), 210 (15) and 135 (100). 13d. Yield: 92%, mp 165¡¾167 8C (colorless white needles from ethanol) (Found: C, 58.4; H, 4.5; N, 16.6. C20H18ClN5O3 requires C, 58.32; H, 4.40; N, 17.01%); max/cm¢§1 3410, 3200, 1745, 1680; lmax/nm (log e in ethanol) 228 (4.25) and 296 (4.18); dH 11.30 (s, br, 1 H), 9.60 (s, 1 H), 7.40 (d), 7.40¡¾7.30 (m, 5 H), 7.12 (d, 2 H), 3.60 (s, 4 H) and 2.95 (s, 3 H); dC 187.6, 161.8, 150.4, 149.5, 140.6, 133.2, 131.8, 128.8, 127.9, 127.8, 127.6, 126.2, 88.2, 51.9, 41.7 and 33.4; m/z (EI) 411 (Ma, 2%), 327 (4), 292 (4), 273 (4), 214 (6), 139 (45) and 119 (100).General Procedure for the Preparation of 14.�¢A suspension of PTAD (1 mmol) in CH2Cl2 (5 cm3) was added to a stirred solution of heterocyclic ketene aminals 7 (1 mmol) in CH2Cl2 (10 cm3) at ¢§60 8C.The colour of PTAD faded within 0.5 h and white solid products precipitated from the solution. After being ¢çltered o€ and washed thoroughly with ethanol, pure products 14 were obtained. 14a. Yield: 58%, mp 156¡¾158 8C (white solid from ethanol) (Found: C, 63.4; H, 5.1; N, 18.3. C20H19N5O3 requires C, 63.65; H, 5.07; N, 18.56%); max/cm¢§1 3420, 3230, 1755 and 1690; lmax/nm (log e in ethanol) 290 (4.03); dH 10.85 (s, 1 H), 10.82 (s, br, 1 H), 7.62 (s, 1 H), 7.62 (s, 1 H), 7.10¡¾7.50 (m, 10 H), 3.38 (t, 4 H), 1.86 (quin, 2 H); dC 186.4, 158.4, 151.3, 151.2, 142.5, 132.7, 130.0, 129.5, 129.2, 128.3, 127.0, 126.4, 91.2, 41.1, 38.5 and 20.1; m/z (FAB) 378 (M a 1)a; m/z (EI) 359 (29%), 317 (23), 243 (54) and 227 (100). 14b. Yield: 72%, mp 158¡¾160 8C (white solid from ethanol) (Found: C, 64.1; H, 5.5; N, 17.7. C21H21N5O3 requires C, 64.43; H, 5.41; N, 17.89%); max/cm¢§1 3420, 3230, 1755 and 1690; lmax/nm (log e in ethanol) 292 (4.06); dH 10.92 (s, br, 1 H), 10.82 (s, 1 H), 7.60 (s, 1 H), 7.43 (d, 2 H), 7.16 (d, 2 H), 7.06¡¾7.38 (m, 5 H), 3.32 (t, 4 H), 2.26 (s, 3 H) and 1.88 (quin, 2 H); dC 185.4, 157.7, 150.5, 150.2, 139.4, 137.5, 132.5, 128.6, 128.0, 127.3, 126.1, 125.9, 89.8, 40.8, 37.7, 21.0 and 19.6; m/z (EI) 373 (3%), 331 (2), 257 (38), 227 (30) and 119 (100). 14c. Yield: 61%, mp 153¡¾155 8C (white solid from ethanol) (Found: C, 61.7; H, 5.1; N, 17.1. C21N21N5O4 requires C, 61.90; H, 5.20; N, 17.19%); max/cm¢§1 3420, 3230, 1755 and 1690; lmax/nm (log e in ethanol) 298 (3.89); dH 11.00 (s, 1 H), 10.84 (s, br, 1 H), 7.58 (s, 1 H), 7.40 (d, 2 H), 7.20¡¾7.36 (m, 5 H), 6.82 (d, 2 H), 3.72 (s, 3 H), 3.38 (t, 4 H) and 1.88 (quin, 2 H); dC 184.8, 157.7, 150.5, 150.1, 159.4, 134.6, 132.6, 128.6, 127.6, 127.4, 126.2, 112.8, 89.6, 55.1, 37.9, 37.6 and 19.7; m/z (EI) 389 (4%), 347 (4), 273 (77), 27 (23) and 135 (100). 14d.Yield: 75%, mp 171¡¾173 8C (white solid from ethanol) (Found: C, 58.2; H, 4.8; N, 16.7.C20H18ClN5O3 requires C, 58.32; H, 4.40; N, 17.01%); max/cm¢§1 3420, 3230, 1760 and 1690; lmax/nm (log e in ethanol) 292 (4.05); dH 10.90 (s, 1 H), 10.76 (s, br, 1 H), 7.70 (s, br, 1 H), 7.40 (d, 2 H), 7.18¡¾7.36 (m, 5 H), 7.17 (d, 2 H), 3.36 (t, 4 H) and 1.86 (quin, 2 H); dC 183.9, 157.4, 150.4, 150.1, 140.8, 132.7, 132.3, 128.5, 127.7, 127.4, 127.3, 126.0, 89.7, 37.6, 37.5 and 19.4; m/z (EI) 393 (19%), 351 (9), 277 (30) and 227 (100). Reaction of Heterocyclic Ketene Aminal 7a with PTAD at Room Temperature.�¢This followed the same procedure for the synthesis of 12 and 13, reaction of 7a with 9 gave a viscous yellow solution.After the removal of solvent, the residue was recrystallized in ethanol to give benzoylphenylurea as white needles. Yield: 73%, mp 208¡¾210 8C (lit.8 208¡¾209 8C); max/cm¢§1 3210 and 1685; H 10.96 (s, 1 H), 9.72 (s, br, 1 H), 7.10¡¾8.10 (m, 10 H); C 168.7, 152.2, 137.2, 133.3, 132.1, 129.0, 128.8, 128.1, 124.4 and 120.5. We thank the National Natural Science Foundation of China for ¢çnancial support. Received, 24th February 1998; Accepted, 8th April 1998 Paper E/8/01566J References 1 For reviews of ene reactions, see (a) W. Carruthers, Cycloaddition Reactions in Organic Synthesis, Pergamon Press, Oxford, 1990; (b) B. B. Snide, Ene Reactions With Alkenes as Enophiles in Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, vol. 5, ch. 1.1. 2 P. C. Montevecchi and M. L. Navacchia, J. Org. Chem., 1995, 60, 6455. 3 J. Cossy, A. Bouzide and M. Pfau, J. Org. Chem., 1997, 62, 7106. 4 J. E. Baldwin, R. M. Adlington, A. U. Jain, J. N. Kolhe and M. W. D. Perry, Tetrahedron, 1986, 42, 4247. 5 M.-X. Wang and Z.-T. Huang, J. Org. Chem., 1995, 60, 2807 and references therein. 6 Z.-T. Huang and M.-X. Wang, J. Chem. Soc., Perkin Trans. 1, 1993, 1085. 7 Org. Synth., 1988, Coll. Vol. 6, p. 936. 8 M.-Z. Deng, P. Caubere, J. P. Senet and S. Lecolier, Tetrahedron, 1988, 44, 6079. J. CHEM. RESEARCH (S), 1998
ISSN:0308-2342
DOI:10.1039/a801566j
出版商:RSC
年代:1998
数据来源: RSC
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Sodium Hydroxide: a Mild and Inexpensive Catalyst for the Regioselective Synthesis of 2-Substituted 5-Methylthiazolo[3,2-b]-s-triazoles‡ |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 8,
1997,
Page 488-489
Majid. M. Heravi,
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摘要:
Sodium Hydroxide: a Mild and Inexpensive Catalyst for the Regioselective Synthesis of 2-Substituted 5-Methylthiazolo[3,2-b]-s-triazoles$% Majid. M. Heravi*a and Mahmood Tajbakhshb aChemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Iran bDepartment of Chemistry, University of Mazandaran, Iran The facile and regioselective synthesis of 2-substituted 5-methylthiazolo[3,2-b]-s-triazoles has been performed by the catalytic action of NaOH on 3-propynylthio-s-triazoles.Thiazolo[3,2-b]-s-triazoles 3 were Rrst synthesized by Potts and Hussain1 via the reaction of 1 with chloroacetone and subsequent dehydration of the corresponding ketone in the presence of POCl3. In 1978, Srinvasan and co-workers2 reported the synthesis of 5-arylprop-3-ynlthio-s-triazoles 2 in moderate yields, through the reaction of 1 with propynyl bromide, in the presence of sodium acetate. Further annula- tion of 2 to give thiazolo [3,2-b]-s-triazoles has been also reported under mercury(II) acetate catalysis in poor to moderate yields.2 In the above attempt to prepare 22, through use of 1, propynyl bromide and alkali, the moderate yields obtained perhaps is due to formation of 3-allenylthio substituted s-triazole derivatives via the intermediacy of an s-propynyl derivative 2.Here, we report a simple and ecient synthesis of 3-propynylthio-s-triazoles 2 and regioselective cyclization of the latter to give 3 in moderate to high yields.When compound 1 (R a Me) was condensed with propynyl bromide in re�Puxing absolute ethanol in the absence of base, prop-3-ynylthio-s-triazole 2 (R a Me) was obtained, mp a 126 8C. In the 1H NMR spectrum of this compound methylene protons appear as a doublet and the acetylenic proton as triplet showing a long range coupling (J a 2.4 Hz). To establish the generality of method, several 5-substituted 3-thio-s-triazoles 1 were employed and condensed with propynyl bromide to a€ord 2 in good to excellent yields (Table 1).For cyclization of 2 (R a Ph) in moderate yield, Srinvasan and co-workers used mercury(II) acetate which is poisonous and expensive. However the use of 1 M sodium hydroxide solution for cyclization obviated these disadvantages and regioselective cyclization occurred to give the desired products in much better yield. Thus when 2 (R a Me) was re�Puxed in 1 M sodium hydroxide solution with subsequent neutralization a single (TLC) compound was obtained.Its 1H NMR showed signals at d 2.5 (d, J a 1.5 Hz 3 H, Me), 2.6 (s, 3 H, Me), 6.5 (q, J a 1.5 Hz, CH of thiazole). Although fusion of thiazole and the triazole nuclei can occur in two di€erent ways to give thiazolo[3,2-b]-s- triazole 3 and thiazolo[2,3-c]-s-triazole 4, from analytical, spectral and melting point data as well as by comparison with an authentic sample, the product was identiRed as 2,5-dimethylthiazolo[3,2-b]-s-triazole 3 (R a Me). This indi- cates that sodium hydroxide has smoothly catalyzed regio- selective cyclization and isomerization of the acetylenic moiety of the propynylthio group.The reaction proceeds via 5-exo-diagonal cyclization3 followed by isomerization and aromatization4�}6 A mechanism is suggested in Scheme 1. Various prop-3-ynylthio-s-triazoles 2 were employed in order to prepare condensed thiazoles and to establish the generality of method. We found that one-pot cyclization and aromatization of 2 to 3 can be carried out in high regioselectivity and excellent yields.Melting points are reported in Table 2. In conclusion in comparison with the presently available synthetic methods1,2 which show drawback's from the stand point of yields, price and limited availability of catalyst or low regioselectivity, the eciency of the present method is apparent from the availability of inexpensive sodium hydroxide and the unique regioselectivity as well as high yield with lack of side products.Owing to the simplicity of the conditions and use of inexpensive catalyst this method- ology should Rnd utility in organic synthesis. Experimental Melting points (uncorrected) were obtained on a Koer Hazbank Rischart type 4841 apparatus. The 1H NMR spectra were obtained on a Varian 60A spectrometer and mass spectra were scanned on a Varian Mat CH-7 instrument at 70 eV. Preparation of 5-Substituted 3-Propynylthio-s-triazoles (2) (Typical Procedure).DAn appropriate 3-thioxo-s-triazole (5 mmol) was dis- solved in ethanol (50 ml) to which was added propynyl bromide (5 mmol) dropwise. This mixture was re�Puxed for 3 h.After evapor- ation of solvent and pouring the residue into crushed ice, the solid that separated was Rltered and crystallized from a suitable solvent (see Table 1). J. Chem. Research (S), 1998, 488�}489$ Table 1 Synthesis of prop-3-ynylthio-s-triazoles (2a�}g) Product R Yield (%) Mpa/8C Recrystallisation solvent 2a H 68 109 ethanol 2b Me 59 126 ethanol 2c Ph 72 127 (128) benzene 2d o-MeC6H4 71 144 (145) benzene 2e p-MeC6H4 68 92 (90) benzene 2f o-ClC6H4 75 85 (84) benzene 2g p-ClC6H4 67 144 (145) benzene a1st values, 2nd in parentheses.$This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). %This paper is dedicated to Professor A. ShaRee on the occasion of his 60th birthday. *To receive any correspondence. 488 J. CHEM. RESEARCH (S), 1998Selected Data for 2a.H ([2H6]DMSO) 3.05 (t, J 2.4 Hz, 1 H,2CH), 3.9 (d, J 2.4 Hz, 2 H, CH2), 8.45 (s, 1 H, CH of triazole).IR (KBr disc), v 3240, 2850, 2500, 2110 cm£¾1; m/z (%) 139(4),138(6), 137(48), 110(76), 84(51), 38(80), 32(67), 28(100).Selected Data for 2b.H ([2H6]DMSO) 2.5 (t, J 2.4 Hz, 1 H,2CH), 2.7 (s, 3 H, CH3), 4.0 (d, J 2.4 Hz, 2 H, CH2). IR (KBrdisc), v 3230, 2500, 2850, 2100 cm£¾1; m/z (%) 153 (4), 159(20), 150(79), 149 (65), 110 (70), 84 (54), 28 (100).Selected Data for 2c.H (CDCl3), 2.35 (t, J 2.4 Hz, 1 H,2CH), 4.0 (d, J 2.4 Hz, 2 H, CH2), 7.45¡Ó7.70 (m, 5 H, Ph).IR(KBr disc), v 3300, 2500, 2850 cm£¾1; m/z (%) 215 (10), 213 (3), 212(18), 211 (18), 102 (19), 32 (27), 28 (100).Preparation of 2-Substituted 5-Methylthiazolo[3,2-b]-s-triazoles (3)(Typical Procedure).An appropriate prop-3-ynylthio compound 2(0.01 mol) was dissolved in 1 M NaOH (20 ml) and the mixturereuxed for 2 h.The reaction mixture was cooled to room tempera-ture and neutralized by addition of HCl. The solid was ltered oand crystallized from suitable solvent (see Table 2).Selected Data for 3a.H (CDCl3), 2.6 (d, J 1.5 Hz, 3 H,CH3), 6.7 (q, J 1.5 Hz, 1 H, CH of thiazole ring), 8.25 (s, 1 H,CH of triazole ring). IR (KBr disc), v 3050, 1480, 1400, 1180,650 cm£¾1; m/z (%) 139 (2), 138 (13), 136 (100), 110 (70), 66 (67), 32(39), 27 (25), 28 (98), 16 (30).Selected Data for 3b.H (CDCl3) 2.5 (d, J 1.5 Hz, 3 H, CH3),2.6 (s, 3 H, CH3), 6.55 (q, J 1.5 Hz, 1 H, CH of thiazole ring). IR(KBr disc), v 3070, 3020, 3000, 1580, 1500 cm£¾1; m/z (%) 153 (5),152 (10), 151 (100), 110 (32), 70 (23), 66 (56), 44 (23), 28 (23).Selected Data for 3c.H(CDCl3) 2.55 (d, J 1.5 Hz, 3 H, CH3),6.55 (q, J 1.5 Hz, 1 H, CH of thiazole ring), 7.3¡Ó7.6 (m, 3 H ofPh), 8.83 (m, 2 H of Ph).IR (KBr disc), v 3100, 1475, 1450, 1320,1280, 710 cm£¾1; m/z (%) 215 (4), 212 (100), 142 (35), 101 (46), 70(95), 32 (54).Received, 13th March 1998; Accepted, 11th May 1998Paper E/8/02038HReferences1 K.T. Potts and S. Hussain, J. Org. Chem., 1971, 36, 10.2 Pramod Upadhyaya, T. G. Surendra Nath and V. R. Srinvasan,Synthesis, 1978, 288.3 J. E. Baldwin, J. Chem. Soc., Chem. Commun., 1976, 434.4 M. M. Heravi and M. Bakavoli, J. Chem. Res. (S), 1995, 11, 480.5 M. M. Heravi, M. Shafaie, M. Bakavoli, M. M. Sadeghi andA. R. Khoshdast, Indian J. Chem., Sect. B, 1996, 35, 1260; Chem.Abstr., 1996, 126, 1442,44a.6 M. M. Heravi, K. Aghapoor, M. A. Nooshabadi and M. M.Mojtahedi, Monatsh. Chem., 1997, 128, 1143.Table 2 Synthesis of 2-substituted 5-methylthiazolo[3,2-b]-s-triazoles (3a¡Óg)Product R Yield (%) Mp/8C Recrystallisation solvent3a H 95 66¡Ó70 ethanol3b Me 92 69¡Ó70 (lit.,1 68¡ethanol3c Ph 90 124¡Ó125 (lit.,1 123) chloroform3d o-MeC6H4 85 84¡Ó85 (lit.,2 85) chloroform3e p-MeC6H4 80 142 (lit.,2 141) methanol3f o-ClC6H4 90 84¡Ó85 (lit.,2 82) chloroform3g p-ClC6H4 80 117¡Ó118 (lit.,2 118) chloroformJ. CHEM. RESEARCH (S), 1998 489
ISSN:0308-2342
DOI:10.1039/a802038h
出版商:RSC
年代:1998
数据来源: RSC
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65. |
N,S Ligands for Preconcentration or Elimination of Heavy Metals. Synthesis and Characterisation of Aminoethanethiols and Aminoethanethiol-modified Silica Gel |
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Journal of Chemical Research, Synopses,
Volume 0,
Issue 8,
1997,
Page 490-490
Carole Bresson,
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摘要:
N,S Ligands for Preconcentration or Elimination of Heavy Metals. Synthesis and Characterisation of Aminoethanethiols and Aminoethanethiol-modified Silica Gel Carole Bresson, Marie-Joe¡í lle Menu,* Miche¢® le Dartiguenave and Yves Dartiguenave Laboratoire de Chimie Inorganique, Universite¡� P. Sabatier, 118 Route de Narbonne, F-31062 Toulouse-Cedex, France Molecular (N,S) aminothiols R(CH2)3NH(CH2)2SH (1), R(CH2)3NH(CH2CHMe)SH (2), R(CH2)3NH(CH2)2S(CH2)2SH (3), R(CH2)3NH(CH2CHMe)S(CH2CHMe)SH (4) and R(CH2)3N[(CH2)2SH]2 (5) [Ra (EtO)3Si] have been prepared by a one step reaction of olefin sulfide on aminopropyltriethoxysilane and characterised by physicochemical methods; the grafting of 1 on silica is reported.During the last decade, much of the current interest in the synthesis and metal coordination of multidentate aminothiol (N, S) ligands1 was related to their application in bio- inorganic chemistry (enzyme modelisation) and in medical imaging. More recently, the use of these ligands was extended to environmental problems, ¢çrst because of their good complexing properties towards heavy metals such as Zn, Cd or Hg which allowed metal depollution and secondly because they can be functionalised by a triethoxysilane group and thus easily grafted on a silica support to give supported molecular traps.5 We have, in a long term objective, performed the syn- thesis of a series of tuneable aminothiol ligands directed to heavy metal speciation, concentration or elimination. Here we describe the synthesis of the ligands resulting from the one-step reaction directed from the reaction of ole¢çn sul¢çde on aminopropyltriethoxysilane (Scheme 1).Five compounds were isolated as liquids, after fractional distillation and characterised by spectroscopic data. 1, 2 and 5 resulted from the monoinsertion (1,2) and diinsertion (5) reaction of the ole¢çn sul¢çde in the N0H bond while 3 and 4 were obtained by the more unusual double insertion reaction of the ole¢çn sul¢çde in the N0H a S0H bonds.The yields depend on the reaction stoichiometry and the steric hindrance of the ole¢çn sul¢çde (R a H, Me). They range from 80% for 2 to 33% for 3. Compound 1 was grafted on silica (Silica Gel Merck 60 230¡¾400 Mesh) by triethoxysilane hydrolysis. The 13C CPMAS NMR spectrum of the solid indicated that 1 is not grafted on the silica through all the ethoxy groups since the presence of a free SiOEt group is clearly apparent.24 No change in the donor atoms of 1 is observed after graft- ing as indicated by comparing the IR spectra of the solid [v(NH) 3312 cm¢§1; v(SH) 2580 cm¢§1] and pure compound [v(NH) 3307 cm¢§1, v(SH) 2557 cm¢§1].A grafting yield of 0.9 mmol g¢§1 was determined from elemental analysis, which agrees with literature data.12a,23 Techniques used: 1H and 13C NMR, MS, 13C CPMAS NMR, elemental analysis References: 25 Tables: 3 (yields for ethylene sul¢çde and propylene sul¢çde; 13C NMR) Figures: 2 (13C-DEPT NMR, Raman spectra) Schemes: 5 Received, 23rd February 1998; Accepted, 5th May 1998 Paper E/8/01521J References cited in this synopsis 1 (a) L.F. Lindoy, Coord. Chem. Rev., 1969, 4, 41 and references cited therein; (b) M. Akbar Ali and S. E. Livingstone, Coord. Chem. Rev., 1974, 13, 101 and references cited therein. 5 (a) G. Bandoli and T. I. A. Gerger, Inorg. Chim. Acta, 1987, 126, 205; (b) D. Yoon Chi and J. A. Katzenellenbogen, J. Am. Chem. Soc., 1993, 115, 7045. 12 (a) K. Oshima, H. Watanabe and K. Haraguchi, Anal. Sci., 1986, 2, 131. 23 (a) M. S. Iamamoto and Y. Gushiken, Analyst, 1989, 114, 983; (b) O. I. Voroshilova, A. V. Kiselev and Y. S. Nikitin, Kollodnyi Zh., 1980, 42, 223; (c) Y. Gushiken and W. C. Moreira, Colloids Surf., 1987, 25, 155; (d) S. Akman, H. Ince and U E . Ko E kluE , Anal. Sci., 1991, 7, 799; (e) M. Grote, A. Schwalk and A. Kettrup, Fresenius Z. Anal. Chem., 1982, 313, 297; ( f ) S. Akman, H. Ince and U E . Ko E kluE , J. Anal. Atom. Spectrosc., 1992, 7, 187. 24 J. BluE mel, J. Am. Chem. Soc., 1995, 117, 2112. J. Chem. Research (S), 1998, 490 J. Chem. Research (M), 1998, 1919¡¾1932 Scheme 1 *To receive any correspondence. 490 J. CHEM. RESEARCH (S), 19
ISSN:0308-2342
DOI:10.1039/a801521j
出版商:RSC
年代:1998
数据来源: RSC
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