摘要:

N N Me CHO Ph NH2 1 N N Me Ph 11 N CN NH2 N N Me Ph NH2 3 OH H H CONHY C N NCCH2CONHY N N Me Ph 4 N CONHY NH H H OH H 2a 2a,b N N Me Ph 5a,b N CONHY NH2 –H2O 2,5 a b H NH2 Y N N Me Ph 12 N CN Ph N N Me Ph 13 N NHCOPh O H N N Me Ph 14 NHCO2Et CHO 1 PhCOCH2CN (8) ClCO2Et (10) PhCONHCH2CO2H (2) CH2(CN)2 (7) N N Ph Me NH CN O 6 N N Me Ph N CN X OH H N N Me Ph NH EtO CN X 1 + 11 X = CN X = CO2Et –HCN N N Me Ph N X OH CHO CH C CN X 18a X = CO2Et b X = CN 15,16 a b X CO2Et CN CN X Ar 1 + N N Me Ph N X OH 20 X = CO2Et X = CN 11 6 X = CO2Et, CN 19 Ph p-anisyl p-ClC6H4 2-furyl 2-thienyl Ph p-anisyl p-ClC6H4 2-furyl 2-thienyl CN CN CN CN CN CO2Et CO2Et CO2Et CO2Et CO2Et a bc def gh ij Ar X Ar 19 16 17 15 20 J.CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 20–21 J. Chem. Research (M), 1998, 0231–0241 Polycyclic Pyrazoles: Routes to New Pyrazoloazines Abdel M. Hussein*a and T. I. El-Emaryb aChemistry Department, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt bChemistry Department, Faculty of Science, Assiut University, Assiut 71516, Egypt A number of substituted pyrazolo[3,4-b]pyridines and pyrazolo[4p,3p:5,6]pyrido[2,3-d]-pyrimidinones and -1,2,3 -triazinones have been made, starting from 5-amino-3-methyl-1-phenylpyrazole-4-carbaldehyde. Pyrazoles have been found to be excellent precursors for the syntheses of condensed polyfunctionally substituted pyrazoles. 10–11 We report here the facile synthesis of some new pyrazolo[3,4-b]pyridines from 5-amino-3-methyl-1-phenylpyrazole- 4-carbaldehyde (1) which was first described by H�aufel and Breitmaier.12 Cyclocondensation of 1 with cyanoacetamide (2a) in refluxing ethanolic piperidine yielded a product which could have been either the cyano-pyridone 6 or the amino-amide 5a (Scheme 1).Structure 5a was considered to be the only reaction product on the basis of spectroscopic data. Compound 1 also reacted with cyanoaceto hydrazide 2b to yield the pyrazolo[3,4-b]pyridine 5b.Similarly 1 reacted with malononitrile (7) in refluxing ethanolic piperidine to yield the corresponding pyrazolopyridine 11 via addition followed by elimination of water. In analogy, cyclocondensation of 1 with benzoylacetonitrile (8) afforded the pyrazolopyridine derivative 12. The reaction of 1 with hippuric acid was also investigated. Thus, cyclocondensation of 1 with hippuric acid (9) in glacial acetic acid afforded the pyrazolopyridine 13. Also, the reaction of 1 with ethyl chloroformate 10 in ethanolic piperidine yielded the urethane 14.Compound 1 reacted with ethyl ethoxymethylidenecyanoacetate (15a) to yield the substitution product 16 (Scheme 2). Efforts to cyclize 16 under various reaction conditions failed. Also, ethoxymethylidenemalononitrile (1b) failed to yield 18 in reaction with 1, compound 11 instead being formed under the reaction conditions. Efforts to cyclize 1 with arylmethylidenes 19a–j to afford 20a–j were not successful; instead, 6 and 11 were isolated.12 Synthetic approaches to aminocarboxamide derivatives have been extensively studied, and many syntheses using aminocarboxamides as starting materials have been reported.13–16 We found that the aminocarboxamide 5a reacted with urea derivatives to yield the pyrazolopyridopyrimidine derivatives 22a,b (Scheme 3).Similarly, formic acid, acid chlorides, aryl aldehydes and phenyl isothiocyanate reacted with 5a to give *To receive any correspondence.Scheme 1 Scheme 2N N N N NH Me O X H Ph 22a X = O b X = S N N N N NH Me O Ph 25a R = H b R = Me c R = CH2Cl R N N N N NH Me O Ph Ar Ar a bc Ph p-ClC6H4 p-anisyl 26,27 N N N N NH Me O Ph NHPh 29 N N N N N NH Me O Ph 30 NH2C(X)NH2 (21) HCO2H (23) RCOCl (24a R = Me b R = CH2Cl) ArCHO (26) PhNCS (28) NaNO2 AcOH 5a 27 J. CHEM. RESEARCH (S), 1998 21 the corresponding pyrazolopyridopyrimidine derivatives 25, 27 and 29 respectively. Treatment of the aminocarboxamide 5a with sodium nitrite in acetic acid at room temperature afforded the 1,2,3-triazinone derivative 30.Techniques used: IR, NMR (1H, 13C), mass spectrometry, microanalysis References: 16 Table 1: Mps, yields and elemental analysis of 5a–c, 11, 12, 13, 14, 16, 22a,b, 25a–c, 27a–c, 29 and 30 Table 2: IR and 1H NMR of 5a,b, 11, 12, 13, 14, 16, 22a,b, 25a–c, 27a–c, 29 and 30 Table 3: 13C NMR of 22a and 27b Received, 2nd June 1997; Accepted, 29th September 1997 Paper E/7/03809G References cited in this synopsis 10 C. R. Hardy, Adv. Hetrocycl. Chem., 1984, 36, 343. 11 M. H. Elnagdi, G. E. H. Elgemeie and R. M. H. El-Moghayar, Adv. Heterocycl. Chem., 1987, 41, 319. 12 J. H�aufel and E. Breitmaier, Angew. Chem., Int. Ed. Engl., 1974, 13, 604. 13 G. M. Coppola and M. J. Shapiro, J. Heterocycl. Chem., 1980, 17, 1163. 14 Y. Imai, S. Sato, R. Takasawa and M. Ueda, Synthesis, 1981, 35. 15 J. Clark and G. Hitiris, J. Chem. Soc., Perkin Trans. 1, 1984, 2005. 16 T. M. Stevenson, F. Kazmierczak and N. J. Leonard, J. Org. Chem., 1986, 51, 616. Sche

ISSN:0308-2342    

DOI:10.1039/a703809g

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

O OR OMe RO OR OR RO H O 1 R = H 1a R = Ac OR H 1 2¢ 3¢ 4¢ 5¢¢ 6 7 8¢¢ 11¢¢ 13¢¢ 3¢¢ 2¢ 4¢¢¢ 1¢¢ 5 R 3 S O OH HO OH HO OMe OH O H H H 3 3 7 R 5 S R O OH HO OH HO OMe OH O H H H 4 S S S S OH H O OH HO H H H 5 and 6 O OH O MeO HO R S R OH HO H HO H O HO OMe OH O 3 S 2 22 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 22–23 J. Chem. Research (M), 1998, 0265–0279 Novel Diarylheptanoids from the Seeds of Alpinia blepharocalyx: Revised Structure of Calyxin A Jeevan Kumar Prasain,a Yasuhiro Tezuka,a Jian-Xin Li,a Ken Tanaka,b Purusotam Basnet,a Hui Dong,c Tsuneo Nambaa and Shigetoshi Kadota*a aResearch Institute for Wakan-Yaku (Traditional Sino-Japanese Medicines), Toyama Medical and Pharmaceutical University, 2630-Sugitani, Toyama 930-01, Japan bNational Research Institute of Police Science, 6 Sanban-cho, Chiyoda-Ku, Tokyo 102, Japan cChina Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, China Calyxins A (1), E (2) and F (3), 6-hydroxycalyxin F (4), Calyxin G and epicalyxin G (5 and 6), novel diarylheptanoids having a chalcone or a flavanone moiety, were isolated from Alpinia blepharocalyx K.Schum. and their structures, including the corrected one of calyxin A (1), were elucidated by spectroscopic methods. As part of our continuing studies on the chemistry of traditional Chinese medicine, we have examined the constituents of Alpinia blepharocalyx K. Schum. (Zingiberaceae). The ethanolic extract obtained from the seeds of A.blepharocalyx showed significant hepatoprotective activity against CCl4- induced hepatotoxicity in rats and, therefore, it was further partitioned with hexane and diethyl ether to give hexane- and ether-soluble fractions. The ether-soluble and residual frac- *To receive any correspondence.J. CHEM. RESEARCH (S), 1998 23 tions exhibited a more significant hepatoprotective effect than others in the same experimental liver injury model. After repeated chromatography with silica gel and Sephadex LH-20, the ether-soluble fraction yielded a series of new diarylheptanoids having the novel feature of a diarylheptanoid part bearing a chalcone or flavanone moiety.In a previous paper,3 we reported the isolation and structure determination of six novel diarylheptanoids named calyxin B, epicalyxin B, calyxin C, epicalyxin C, calyxin D and epicalyxin D from the seeds of A. blepharocalyx. Herein we report the isolation and structure determination of six additional novel diarylheptanoids, calyxins A (1), E (2) and F (3) and 6-hydroxycalyxin F (4) along with a mixture of calyxin G and epicalyxin G (5 and 6).Their structures have been elucidated by spectroscopic methods and the structure of calyxin A (1) has been corrected, as it was reported erroneously in a preliminary communication.4 Calyxin A (1) was obtained as an optically active, light yellow amorphous solid. The formula C35H34O9, determined by high-resolution FAB–MS, and the COSY and HMQC experiments indicated 1 to be a diarylheptanoid bearing a chalcone moiety.The long-range correlations observed in the HMBC spectrum of 1 provided evidence for the attachment of the chalcone moiety to the diarylheptanoid part at the C-5 position. In our preliminary communication,4 the location of the chalcone moiety in 1 was erroneously assigned at C-7. The 13C NMR spectral analysis of 1, together with the inference provided by chemical reaction of an ethanolic KI solution with 1, indicated the presence of one hydroperoxy and five hydroxy groups.5 The absolute stereochemistry at C-3 and C-5 within 1 was determined to be S and R respectively, based on the NMR studies of the a-methoxy-a-tri- fluoromethylphenylacetyl (MTPA) ester of hexamethyldeoxycalyxin A.Calyxins E (2) and F (3) had the molecular formula C35H34O8. The 1H and 13C NMR data of both the compounds were similar to those of 1, but 2 differed from it by having a flavanone moiety, instead of a chalcone, while 3 differed in terms of the diarylheptanoid structure.A tetrahydropyran ring like that of (µ)-centrolobine7 was found in the diarylheptanoid part of 3. The absolute stereochemistry at C-3 of both the compounds was assumed to be S in view of the biogenesis. The relative stereochemistry of the protons at the three chiral centres (C-3, C-5 and C-7) within 3 was deduced to be axial on the basis of their coupling constants and an NOE experiment and the conformation of the tetrahydropyran ring was determined to be a boat-form.The absolute configuration of 3 at other chiral centres is 5R,7R, on the assumption that 3 has the same absolute configuration at C-3 (i.e., S) as that of calyxin A (1). Compound 4 appeared to be 6-hydroxycalyxin F from its spectral data. Calyxin G (5) and epicalyxin G (6) were obtained as an epimeric mixture and their NMR data indicated the presence of the same diarylheptanoid moiety as 3 and the same flavanone moiety as 2. Techniques used: Polarimetry, UV, IR, NMR, MS References: 8 Tables: 2 (1H- and 13C-NMR data for 1–6) Scheme: 1 Figures: 3 Received, 27th August 1997; Accepted, 30th September 1997 Paper E/7/06250H References cited in this synopsis 3 J. K. Prasain, Y. Tezuka, J.-X. Li, K. Tanaka, P. Basnet, H. Dong, T. Namba and S. Kadota, Tetrahedron, 1997, 53, 7833. 3 Preliminary communication: S. Kadota, H. Dong, P. Basnet, J. K. Prasain, G.-J. Xu and T. Namba, Chem. Pharm. Bull., 1994, 42, 2647. 5 F. S. El. Feraly, Y. M. Chan, E. H. Fairchild and R. W. Doskotch, Tetrahedron Lett., 1977, 23, 1973. 7 A. A. Craveiro, A. D. C. Prado, O. R. Gottlieb and P. C. W. De Albuquerque, Phytochemistry, 1970, 9, 1869.

ISSN:0308-2342    

DOI:10.1039/a706250h

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

N HN O O R O HO HO N F ClFCH Et Et + F – , DMF N HN O O R O O HO ClFCH N Et Et F – + 5 N HN O O R O O O ClFCH N Et Et N N O O R O HO 7 (60%) 6 (15–20%) Major path b 1 Minor path a a R = Me b R = H N N O O R O O O F N O Me Me 13 N N O O R O O O F Cl H N N O O R O O ClFCH N Et Et 12 8 F N N O O R O O ClFCH N Et Et OH 11 N N O O R O O ClFCH N Et Et + F – N N O O R O HO 7 a R = Me b R = H N N O O R O F 9 10 24 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 24–25 J. Chem. Research (M), 1998, 0301–0326 The Reaction of 2p-Deoxynucleosides with N-(2-Chloro- 1,1,2-trifluoroethyl)diethylamine: Mechanisms of O2,3p-Anhydro-2p-deoxynucleoside and By-product Formation Raj K.Sehgal* and Joseph G. Turcotte Department of Medicinal Chemistry, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island 02881, USA Reaction mechanisms consistent with the formation of isopropylidene-like trans-furanose-3p,5p-[2-(R)(S)-aminochloro- fluoromethyl-1,3-dioxanyl]-2p-deoxynucleoside intermediates 6, O2,3p-anhydro-2p-deoxynucleosides 7 and other minor reaction products and the yield-limiting effect of 6 on the cyclization of 7 are proposed.In our ongoing efforts to develop anti-HIV liponucleotides with distinct biophysical properties, the synthesis of the immediate anhydro precursors (7a, 7b) of azidothymidine and azidodeoxyuridine via reaction of 2p-deoxynucleoside series of compounds with N-(2-chloro-1,1,2-trifluoroethyl)- diethylamine (CTFDA) was investigated in detail.5a,7,9 We herein report our preliminary findings on the reaction mechanism underlying the formation of O2,3p-anhydronucleosides and by-product analysis envisaged to optimize the reaction conditions for this intriguing transformation. The main features of the proposed mechanism as outlined in Schemes I and II are an equilibrium between the transfuranose intermediates 6 and 5, with the latter iminium species undergoing intramolecular cyclization to form anhydronucleosides 7.To rationalize the formation of the minor novel product *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Scheme I Scheme IIN HN O O R O TsO N3 16 N HN O O R O HO N3 N HN O O R O N3 N3 15 14 N HN O R O HO N3 + O 7 N N O O R O O N N O O R O O ClFCH N Et Et 9 LiN3, DMF N N O O R O O ClFCH N Et Et OH LiN3, DMF O ClFCH N Et Et N N O O R O HO 11 6 a R = Me b R = H – N3 + 17 J.CHEM. RESEARCH (S), 1998 25 13a, analogous intermediates 8a, 9a and 12a are invoked. The extremely acidic hydrogen atom of the chlorofluoromethyl group of 12a is readily removed via base, with the resulting intermediate fluorocarbene inserting into the C·H bond of the solvent (DMF); elimination of hydrogen chloride to the enolate gives rise to the isolated ester 13a (preferred keto form).Azide displacements on the stable bicyclic intermediates 6 with lithium azide in DMF afforded the corresponding disubstituted derivatives 17 (Scheme III) via the likely intermediates 11 and 9. The stereochemical course of the resulting diazido nucleosides having the 3p-a-stereochemistry was ascertained and confirmed by an independent synthetic route. The products of reaction of 2p-deoxycytidine with CTFDA proved too unstable to isolate chromatographically (silica gel). Techniques used: 1H NMR, MS, IR References: 18 Schemes: 4 Received, 5th August 1997; Accepted, 30th September 1997 Paper E/7/05686I References cited in this synopsis 5 (a) R. P. Glinski, M. S. Khan and R. L. Kalamas, J. Org. Chem., 1973, 38, 4299. 7 G. Kowollik, K. Gaertner and P. Langen, Tetrahedron Lett., 1969, 3863. 9 R. L. Rideout, D. W. Barry, S. F. Lehrman, M. H. St. Clair, P. A. Furman, L. M. Beecham II, H. S. LeBlanc and G. A. Freeman, Eur. Pat. Appl., 86301896.6, 1986. Scheme III

ISSN:0308-2342    

DOI:10.1039/a705686i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Me R O NNHAr X CN Ar¢ 1 a bc d Ar Ph C6H4Me- p Ph C6H4Me- p R CO2Et CO2Et COMe COMe 2 a b c def Ar¢ Ph C6H4Cl- p C6H4OMe- p Ph C6H4Cl- p C6H4OMe- p X CN CN CN CO2Et CO2Et CO2Et Ar¢ CO2Et X CNO N HN Ar 1a,b + 2a,f O NNHAr O Ar¢ NC NC N N O CO2Et Ar¢ Ar O N OH Ar¢ N N O CO2Et Ar¢ Ar NC N Ar N N O CO2H Ar¢ Ar Route a Route b X = CN –EtOH X = CO2Et –CH2(CN)CO2Et 3 4 6 5 7 8 5,8 abcdef Ar Ph Ph Ph C6H4Me- p C6H4Me- p C6H4Me- p Ar¢ Ph C6H4Cl- p C6H4OMe- p Ph C6H4Cl- p C6H4OMe- p –HCN CN X H2N CN R Me CN X H2N NNHAr CN NC HN N N Me COMe Ar NH2 X 9a X = CN b X = CO2Et 11 NH O ArHNN Me X CN CN 13a Ar = Ph, X = CN b Ar = C6H4Me- p, X = CN N N N Me CO2Et NH2 Ar X HN N N N Me COMe NH2 Ar X HN 14 12 Ar Ph C6H4Me- p Ph C6H4Me- p X CN CN CO2Et CO2Et N N N Me CO2Et NH2 Ar HO2C HN 16 N N N Me CO2Et NH2 Ar H2NOC HN 15 1c,d R = COMe 1a,b –EtOH R = CO2Et X = CO2Et X = CN Ar = Ph Ar = C6H4Me- p 1 + abcd 26 J.CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 26–27 J.Chem. Research (M), 1998, 0188–0197 Studies on Polyfunctionalised Heteroaromatics: a Novel Synthesis of Polyfunctionalised Pyridine, Pyridazine and Pyrido[2,3-c]pyridazine Derivatives Mohamed Hilmy Elnagdi,*a Magda Abdel-aziz Barsy,b Fawi Mohamed Abdel-Latifb and Kamal Usef Sadek*c aDepartment of Chemistry, Faculty of Science, University of Kuwait, P.O. Box 5969, Safat 13060, Kuwait bDepartment of Chemistry, Faculty of Science, South Valley University, Aswan, Egypt cDepartment of Chemistry, Faculty of Science, Minia University, 61519, Minia, Egypt Ethyl 2-arylhydrazono-3-oxobutyrates react with a,b-unsaturated nitriles to afford either pyridopyridazine or pyridine derivatives depending on the structure of the unsaturated nitrile.As a part of our programme aimed at synthesising pyridazinones with substitution patterns required for a biological chemistry programme, we report here a novel synthesis of several pyridazines and condensed pyridazines which are difficult to obtain through established synthetic routes.11–13 Ethyl 3-oxo-2-phenylhydrazonobutyrate (1a) (Ar=Ph, R=CO2Et) reacted with 2a in the presence of ammonium acetate to yield 3,5-dihydroxy-4-phenylazobiphenyl-2-carbonitrile (5a).The formation of 5a is assumed to proceed through a Michael-type addition of the methyl function in 1a to the activated double bond in 2a, affording the acyclic adducts 3 which then cyclises via loss of ethanol and then aromatise via elimination of HCN to yield 5 (Scheme 1, route a).Similarly 1a reacted with 2b,c and 1b reacted with 2a–c to afford 5b–f, the 1H NMR spectrum for the reaction products revealed in each case a multiplet for aromatic and pentasubstituted benzene protons and two one-proton signals for OH groups. In contrast, the reaction of 1a with 2d afforded a compound of molecular formula C17H12N2O3 [m/z 293 [M+)]. The 1H NMR spectrum of the reaction product revealed only a multiplet at d 7.12–7.77 integrating for aromatic protons.Moreover, we could detect by TLC the presence of ethyl cyanoacetate in the reaction mixture. Structure 8a was suggested for the reaction product. The formation of 8a is assumed to proceed through the intermediacy of the Michael *To receive any correspondence. Scheme 1 Scheme 2J. CHEM. RESEARCH (S), 1998 27 adduct 3 which loses ethyl cyanoacetate via an SN2 displacement into dihydropyridazinone (6) which undergoes hydrolysis and autooxidation under the reaction conditions affording the acid 8a.Similarly, the reaction of 1a with 2e,f and of 1b with 2d–f afforded 8b–f. Compounds 1c,d reacted with 2-amino-1,1,3-tricyanopropene (9a) via a Knoevenagel condensation to yield the intermediate 11, which then cyclised into pyridopyridazines 12a,b. In the reaction of 1c,d with 9b the formed esters were hydrolysed to give the corresponding acids 12c,d by the water eliminated during the condensation step (see Scheme 2).The reaction of 9a with the ethyl arylhydrazonoacetoacetate 1a afforded a mixture (1.2:1) of two products of molecular formulae C16H10N6O (M+=302) and C18H18N6O3 (M+=365), respectively. The former was identified as the pyridine derivative 13a and the latter as the pyridazinecarboxamide 15a. Structural assignments were based on analytical and spectral data. Thus, compound 13a is coloured due to the presence of the hydrazone chromophore which is indicated by a strong UV band at 380 nm.The IR spectrum revealed the presence of a ring CO band at 1680 cmµ1, as well as two cyano bands at 2225 cmµ1. The 1H NMR spectrum of 13a indicated the expected aromatic multiplets, as well as signals at d 8.22 for an NH proton and d 2.35 for a methyl group. The IR spectrum of 15a indicated the presence of bands for amide CO and NH2 groups. The 1H NMR spectrum was also in accordance with the proposed structure. A possible mechanism for the formation of both 13 and 15 is depicted in Scheme 2: in each case a Knoevenagel condensation would yield an intermediate 10, cyclisation of which via the elimination of an ethanol molecule would afford 13, while intramolecular cyclisation and hydrolysis would give 15. Similarly, 13b and 15b were formed from the reaction of 1b with 9a. The reaction of 1a,b with ethyl 3-amino-2,4-dicyanoprop- 2-enoate (9b) afforded only the carboxylic acids 16a,b which are believed to be formed via hydrolysis of the esters 14c,d. Techniques used: 1H NMR, MS References: 13 Received, 9th June 1997; Accepted, 1st October 1997 Paper E/7/03978F References cited in this synopsis 11 M. H. Elnagdi, A. M. Negm and K. U. Sadek, Synlett., 1994, 27 and references cited therein. 12 M. H. Elnagdi, N. S. Ibrahim, K. U. Sadek and M. H. Mohamed, Liebigs Ann. Chem., 1988, 1005. 13 H. A. Awadhi, F. Al-Omran, M. H. Elnagdi, L. Infantes, C. F. Foces, N. Jagerovic and J. Elguero, Tetrahedron, 1955, 12 745.

ISSN:0308-2342    

DOI:10.1039/a703978f

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

O O Ph3P CHCOR + O C OH C O– C H COR COR H CHCOR Ph3P COR C ROC H 6a–d 1 8a–d 9a–d E-10a–d 6,8–10 a R = OMe; b R = OEt; c R = Me; d R = Ph –Ph3PO 6 –Ph3P O Cl Cl O NC NC O Cl Cl O– NC NC O Cl Cl OR NC NC O Cl Cl OH NC NC O Cl Cl OH NC NC OH Cl Cl OH NC NC P OR OR OR P OR OR P OR OR OR OH P(OR)2 O O P(OR)3 13 4 14 15 R = Me 18 14A 17a,b TAPO + A B +H2 O (RO)2P(O)H 16 13–17 a R = Me; b R = Et + –ROH 28 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 28–29 J. Chem. Research (M), 1998, 0327–0339 Comparative Behaviour of 2,6-Di-tert-butyl- and 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone with Some Phosphorus Reagents Wafaa M.Abdou,*a Monier A. I. Salemb and Ashraf A. Sediekb aDepartment of Pesticide Chemistry, National Research Centre, Tahrir St., Dokki, Cairo, Egypt bDepartment of Chemistry, Ain Shams University, Cairo, Egypt 2,6-Di-tert-butyl-1,4-benzoquinone (1) reacts with phosphorus ylides to give alkyl 1-p-hydroxyarylfumarates (ca. 75%); triethyl/methyl phosphites react with 1 and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 4) on oxygen but triisopropyl phosphite reacts with 1 on oxygen and with 4 on carbon.In connection with previous investigations,1,3 we are continuing our study of the interaction of the p-quinones 2,6-di-tertbutyl- 1,4-benzoquinone (1) and 2,3-dichloro-5,6-dicyano- 1,4-benzoquinone (DDQ, 4) with some penta- and tri-valent phosphorus reagents. 1. Reactions of 2,6-Di-tert-butyl-1,4-benzoquinone (1) with Phosphorus Ylides 6a–d.·Treatment of the quinone 1 with 2 mol.equiv. of alkoxy- (6a,b) or b-oxo-alkylidenephosphoranes (6c,d) in dry toluene solution followed by chromatography of the product mixture afforded the corresponding substituted phenols 10a-d in ca. 75% yield (Scheme 1). The reaction of 6c,d with 1 requires a protonating reagent (benzoic acid). The phenols 10a–d were only obtained in the E-configuration and assigned the alkyl 1-p-hydroxyarylfumarate structure.Points in favour of this conclusion are (a) compounds 10 have sharp melting points and did not show any spectral evidence for isomerism; (b) it is generally accepted7–9 that the geometry of the double bond in intramolecular Wittig reaction is usually E; (c) other related examples3,4 of stabilizd ylide reactions with p-quinones lead to either E-stereoselectivity or complete E-stereospecificity in these condensations. Mechanistically, the initially formed p-quinone methane intermedites 8a–d give, by Michael addition of a second ylide species 6, the betaines 9 which eliminate triphenylphosphine to give E-10a–d. 2. Reactions of Quinones 1 and 4 with Trialkyl Phosphites. ·In dichloromethane solution, the products of the reaction of 4 with trimethyl phosphite 13a were the p-alkoxyaryl dialkyl phosphate 15a (18%), the p-hydroxyaryl dialkyl phosphate 17a (20%) and the hydroquinone 18 (45%) (Scheme 2). No methyl chloride or acetonitrile could be detected.The results with triethyl phosphite (13b) were similar, except that the parallel p-ethoxyaryl diethyl phosphate (15; R=Et) was not observed. However the phosphate 17b (28%) and 18 (55%) were isolated by fractional crystallization of the product mixture. These results can be explained via intial attack by phosphorus on oxygen in 4 to yield the phosphonium species 14 which in the case of 13a (R=Me) would allow group translocation, giving the alkyl ether of dialkyl p-hydroxyaryl phosphate 15 (Path A, Scheme 2).Conversely, partial hydrolysis of 14 (adversion water) results in the formation of 17a,b via with intermediate 14A (Path B). On the other hand, the formation of 18 can be explained in terms of the high redox potential of DDQ15a together with the strong reducing character of the tertiary phosphite reagents14 which would facilitate the reduction of 4 with water (unavoidable moisture) to give 18 along with trialkyl phosphate. That 17b and 18 are only formed from the reaction of 13b with 4 can be attributed to the high reduction potential of 13b as compared to its methyl analogue,2,16 which facilitates the other competing reaction (reduction of DDQ) with formation of 18 in a high yield (55%).Conversely, when 4 was allowed to react with triisopropyl phosphite (13c) under the same reaction conditions as used with 13a,b, the reaction went via a different pathway to give the benzoquinone–diisopropyl phosphoante derivative 20 and the hydroquinone monoisopropyl ether 21 in nearly equal amounts (135%) (Scheme 3).It is obvious that carbon attack takes palce in the latter reaction to give the alkoxyphosphonium salt 19, which is then dealkylated by the displaced chloride ion (Michaelis–Arbuzov reaction) to give 20. Meanwhile, initial reduction of DDQ 4 to 18 (see above) and *To receive any correspondence. Scheme 1 Scheme 2OR Cl Cl OH NC NC O Cl O– NC NC O P(OR)2 Cl O NC NC Cl P OR O OR R O 18 + 21 19 20 13c –RCl 4 + P(OR)3 13c c, R = Pri + O– O OR O OH OH HO O P(OR)2 O P(OR)3 P(OR)2 O 23a R = Me b R = Et 24 22a–c 25a–c (R as in 16) 1 P(OR)3 13a–c Path A Path B P(OR)2OH NaOR a R = Me b R = Et c R = Pri 16 J.CHEM. RESEARCH (S), 1998 29 further alkylation of the product with a second molecule of 13c affords the respective monoisopropyl ether 21. Next, the reaction of the trialkyl phosphites 13a–c with 2,6-di-tert-butyl-1,4-benzoquinone (1) was also investigated. The reaction of 1 with trimethyl and triethyl phosphites (13a,b) proceeded smoothly in boiling toluene (3 h) to give the corresponding ether phosphates 23a (72%) and 23b (80%), respectively.With 13c, the same reaction conditions afforded 25c (80%). Hydroquinone 24 was, however, formed in the three reactions (s8%) (Scheme 4). The formation of 25c instead of the parallel 23c is not unexpected in view of the bulky isopropyl group which would impede the Arbuzov reaction. The structures of 23a and 23b were assigned through elemental analysis and by IR, 1H and 31P NMR and mass spectroscopy, but the identity of the known18 compound 25c was established by mp, mixed mp and comparative IR and mass spectra with an authentic sample prepared by the action of diisopropyl phosphite on 1 in the presence of sodium alkoxide.18 Techniques used: Elemental analysis, mass spectrometry, IR, 1H and 31P NMR References: 24 Equations: 6 Schemes: 4 Received, 23rd June 1997; Accepted, 2nd October 1997 Paper E/7/04394E References cited in this synopsis 1 W.M. Abdou, Y. O. Elkhoshnieh and A. A. Kamel, J. Chem. Res., 1996, (S) 326; (M) 1841. 3 W. M. Abdou, M. A. I. Salem and A. A. Sediek, Tetrahedron, 1997, 53, 13 945. 4 H. J. Bestmann and H. J. Lang, Tetrahedron Lett., 1969, 457. 7 B. E. Maryanoff and A. R. Reitz, Chem. Rev., 1989, 89, 863. 8 J. Leonard and G. Ryan, Tetrahedron Lett., 1987, 28, 2525. 9 I. I. Cubero and M. T. P. Lopez-Espinosa, Carbohydr. Res., 1988, 173, 41. 14 G. M. Kosolapoff, Organophosphorus Compounds, Wiley, London, 1950, p. 188. 15 J. Marsh, Advanced Organic Chemistry, Reactions, Mechanisms and Structures, 3rd edn., Wiley, New York, 1985; (a) ch. 15 and 16. 17 D. B. Denney and A. D. Pendse, Phosphorus Sulfur Relat. Elem., 1978, 5, 249. 18 N. A. Mukmeneva, V. Kh. Kadyrova, V. V. Moskva and N. A. Moskva, Zh. Obshch. Khim., 1985, 55, 696 (Chem. Abstr., 1985, 103, 123597). Scheme 3 Scheme 4

ISSN:0308-2342    

DOI:10.1039/a704394e

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

N O CO2Et Me Me 1 N O CO2Et Me 2 N O CH(OH)CO2R2 Me R1 3 OH Me Me OH NH2 + Me OMe O O Cl N O H Me OH OMe Cl Me 4 OH NH R1 •• Cl CO2R2 O Me 12 h r.t N Cl HO CO2R2 OH Me R1 N Cl HO CO2R2 O– Me R1 N OH O CO2R2 R1 Me a b N O O H O OR2 R1 Me 5 N O Me O H O R2 R1 3 a b EtOH NaOEt 30 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 30–31† The Reaction of Ethyl 2-Chloroacetoacetate with 2-(Alkylamino) Alcohols: an Unexpected Formation of the 2-Methyloxazolidine Ring† Lubomir Nechev, Alexander Dobrev,* Ivailo Ivanov and Tzvetanka Cholakova University of Sofia, Faculty of Chemistry, 1126 Sofia, Bulgaria The reaction of 2-(alkylamino) alcohols and ethyl 2-chloroacetoacetate in the presence of sodium alkoxides proceeds with unexpected formation of 2-hydroxy-2-(2-methyloxazolidin-2-yl)acetic esters instead of the aza analogues of carboxin (5,6-dihydro-1,4-oxazines) as previously reported in the literature.Carboxin (2-methyl-5,6-dihydro-1,4-oxathiine-3-carboxanilide) and its 4,4-dioxide analogue are well known as synthetic fungicides and are the active components of many commercially available pesticides with worldwide use.1–3 As part of our efforts to synthesise oxazine analogues of these compounds we became interested in the possibility that they may be prepared by the reaction of 2-chloroacetoacetate derivatives with 2-(alkylamino) alcohols instead of the 2-mercapto alcohols as used in the synthesis of carboxin.4 To our knowledge the only example of such a reaction, which appeared in the literature as a collateral result in another type of investigation, is the interaction of ethyl 2-chloroacetoacetate with 2-(methylamino)ethanol.5 In this case the 5,6-dihydro-1,4-oxazine structure 1 was attributed to the reaction product.Our attempt to repeat the cited reaction under the same conditions as used by Baues and co-workers5 led us to a compound with the same melting point as that reported by the authors.However, its IR and 1H NMR spectra revealed clearly the presence of a hydroxy group in the molecule and its mass spectrum supported a non-dehydrated structure. These observations prompted us to study this interaction in detail. For this purpose we studied the behaviour of 2-(methylamino)- and 2-(ethylamino)-ethanol towards 2-chloroacetoacetic esters. The reaction was carried out under the same reaction conditions as used by Baues. The 1H NMR spectra of the products indicated a signal for an OH group as well as a signal for CH, both appearing as doublets (J 5–6 Hz).After D2O had been added, the signal for the OH disappeared and the doublet for CH turned to a singlet. This fact shows unambiguously that the hydroxy group and the methine proton are connected to the same carbon atom. This conclusion obliged us to reject the structure 2 on a possible reaction products, as may have been suggested from the analogous reaction of 2-chloro ketones with 2-amino alcohols.6,7 This rejection of structure 2 was supported by our failure to transform the products into the corresponding 5,6-dihydro-1,4-oxazines by dehydration in the presence of hydrochloric8 or toluenep- sulfonic acid.9 On the other hand, reaction of methyl 2-chloroacetoacetate with 1-aminopropan-2-ol, in the absence of base, gave the crystalline product 4 (see Scheme 1). This reaction is well known for acetoacetic esters,10–12 but in this case the isolation of 4 shows that the initial attack of the nucleophic nitrogen centre occurs on the carbon atom of the carbonyl group (nucleophilic addition reaction) and not on the one connected to the chlorine atom (nucleophilic substitution reaction).Supported by data from elemental analysis and IR and mass spectroscopy, we concluded that the reaction of 2-(alkylamino) alcohols with 2-chloroacetoacetic esters results, most likely, in products with the corresponding 2-hydroxy- 2-(2-methyloxazolidin-2-yl)acetic acid structure 3.On the basis of all these results we propose a probable mechanism (shown in Scheme 2) for the interaction between 2-chloroacetoacetic esters and 2-(alkylamino) alcohols. The key step is the formation of the epoxide ring. The attack of the OH group on the carbon atom at position 3 (attack ‘a’) leads to products 3. None of the alternative product 5 (attack ‘b’) was observed under these reaction conditions. All compounds 3 were obtained as mixtures of diastereoisomers.The isomeric ratio, determined according to the signals for C·CH3 for both isomers in the 1H NMR spectra, is about 4:1 in all cases. The reaction products, initially obtained as oils, crystallized and after two recrystallizations *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 Scheme 2J. CHEM. RESEARCH (S), 1998 31 from light petroleum the diastereoisomer A was obtained pure. In the case of 3b, column chromatography of the residual oil allowed separation of the two isomers A and B. Experimental Melting points were determined on a Boetius hot-stage microscope and were uncorrected. 1H NMR spectra were recorded on Brucker AVANCE DRX-250 (250 MHz) and Tesla BS 487 C (80 MHz) spectrometers and IR spectra on a Specord 75 IR spectrometer. Column chromatography was carried out using 0.032–0.063 mm silica gel (Merck) and with cyclohexane–acetone (3:1 v/v) as mobile phase.Light petroleum used for recrystallizations was the fraction of bp range 50–70 °C. M e t h y l 2 - C h l o r o - 3 ( 2 - h y d r o x y p r o p y l a m i n o ) b u t - 2 - e n o a t e ( 4) . — Methyl 2-chloroacetoaceate (21.1 g, 180 mmol) was added dropwise with stirring (1.5 h) to 1-aminopropan-2-ol (28.1 g, 375 mmol). The reaction mixture was stirred for 12 h at room temperature and heated for an additional 1 h at 50 °C. The resulting red oil was extracted several times with diethyl ether (700 ml). The solvent was evaporated and the resulting yellow oil crystallised.Recrystallisation from water gave the chloro ester 4 as colourless crystals (24.3 g, 65%), mp 86–88 °C, vmax/cmµ1 (CHCl3) 3645 (OH), 3320 (NH), 1660 (C�O), 1600 (C�C); dH (CDCl3, 80 MHz) 1.25 (3 H, d, J 6.0 Hz, CH3CH), 2.22 (3 H, s, CCH3), 2.75 (1 H, br s, OH), 3.28 (2 H, m, NCH2), 3.75 (3 H, s, OCH3), 4.03 (1 H, m, CHCH3); m/z (EI) 208 (MH+) (Found: C, 47.07; H, 6.94; N, 6.68.C8H4ClNO3 requires C, 46.27; H, 6.94; N, 6.68%). General Procedure for the Synthesis of 2-Hydroxy-2-(2-methyloxazolidin- 2-yl)acetic Esters (3).·To a stirred alcohol (methanol or ethanol) solution of the corresponding amino alcohol (125 mmol) was added dropwise a solution of 2-chloroacetoacetic ester (63 mmol) in anhydrous alcohol. The reaction mixture was stirred for 12 h at room temperature and sodium alkoxide (methoxide or ethoxide), obtained from 1.38 g sodium and 50 ml anhydrous alcohol, was then added.After refluxing for a further 1 h, the alcohol was evaporated in vacuo and water was added. The mixture was extracted with chloroform (3Å100 ml), dried (MgSO4) and the solvent was evaporated. The crude product was distilled in vacuo to give the analytically pure compounds. Ethyl 2-(2,3-dimethyloxazolidin-2-yl)-2-hydroxyacetate (3a). 2-(Methylamino)ethanol (9.4 g, 125 mmol) was treated with ethyl 2-chloroacetoacetate (10.4 g, 63 mmol) to give the ethyl ester 3a (7.67 g, 60%), bp 116–120 °C at 0.05 Torr, mp 102–104 °C (from light petroleum), vmax/cmµ1 (CHCl3) 3415 (OH), 1680 (C�O); dH (CDCl3, 250 MHz) 1.16 (3 H, t, J 7.0 Hz, CH3CH2), 1.50 (3 H, s, CCH3), 3.06–3.14 (1 H, m, 4-H), 3.11 (3 H, s, NCH3), 3.48 (2 H, m, CH2CH3), 3.62 (1 H, m, 4-H), 3.75–3.92 (2 H, m, 2Å5-H), 4.25 (1 H, d, J 5.4 Hz, H-a), 4.45 (1 H, d, J 5.4 Hz, OH); m/z (CI) 204 (MH+) (Found: C, 53.74; H, 8.13; N, 6.90.C9H17NO4 requires C, 53.19; H, 8.43; N, 6.89%). Methyl 2-(2,3-dimethyloxazolidin-2-yl)-2-hydroxyacetate (3b). 2-(Methylamino)ethanol (9.4 g, 125 mmol) was treated with methyl 2-chloroacetoacetate (9.48 g, 63 mmol) to give thyl ester 3b (6.2 g, 52%), bp 118–122 °C at 0.05 Torr, mp 82–84 °C (from light petroleum); vmax/cmµ1 (CHCl3) 3410 (OH), 1685 (C�O) (Found: C, 50.89; H, 7.86; N, 7.35. C8H15NO4 requires C, 50.78; H, 7.99; N, 7.40%).Two isomers were separated by column chromatography on silica gel (cyclohexane–acetone, 3:1 v/v). Isomer A, RF 0.22, had mp 82–84 °C (from light petroleum) dH (CDCl3, 250 MHz) 1.49 (3 H, s, CCH3), 3.07–3.15 (1 H, m, 4-H), 3.11 (3 H, s, NCH3), 3.22 (3 H, s, OCH3), 3.61–3.93 (3 H, m, 4-H, 2Å5-H), 4.26 (1 H, d, J 5.3 Hz, H-a), 4.45 (1 H, d, J 5.3 Hz, OH). Isomer B, RF 0.15, was an oil, nD 1.4837; dH (CDCl3, 250 MHz) 1.29 (3 H, s, CCH3), 3.09 (3 H, s, NCH3), 3.23–3.36 (1 H, m, 4-H), 3.33 (3 H, s, OCH3), 3.61–3.90 (3 H, m, 4-H, 2Å5-H), 4.10 (1 H, d, J 6.0 Hz, OH), 4.44 (1 H, d, J 6.0 Hz, H-a).Methyl 2-(3-ethyl-2-methyloxazolidin-2-yl)-2-hydroxyacetate (3c). 2-(Ethylamino)ethanol (11.1 g, 125 mmol) was treated with methyl 2-chloroacetoacetate (9.48 g, 63 mmol) to give the methyl ester 3c (6.15 g, 48%), bp 108–115 °C at 0.05 Torr, mp 77–80 °C (from light petroleum), vmax/cmµ1 (CHCl3) 3410 (OH), 1675 (C�O); dH (CDCl3, 80 MHz) 1.20 (3 H, t, CH3, J 6.8 Hz). 1.39 (3 H, s, CCH3), 3.38 (3 H, s, OCH3), 3.48–4.13 (6 H, m, 2Å4-H, 2Å5-H, CH2CH3), 4.11 (2 H, m, H-a, OH) (Found: C, 53.50; H, 8.39; N, 6.84. C9H17NO4 requires C, 53.19; H, 8.43; N, 6.89%). Received, 17th April 1997; Accepted, 17th September 1997 Paper E/7/02638B References 1 B. von Schmeling and M. Kulka, Science, 1966, 152, 659. 2 B. von Schmeling, M. Kulka, D. S. Thiara and W. A. Harrison, U.S. Pat., 3249499, 1966 (Chem. Abstr., 1966, 65, 7190g). 3 M. Kulka, Can. J. Chem., 1980, 58, 2044. 4 B. von Schmeling, M. Kulka, D. S. Thiara and W. A. Harrison, U.S. Pat., 3393202, 1968 (Chem. Abstr., 1967, 66, 95055w); U.S. Pat., 3399214, 1968 (Chem. Abstr., 1968, 68, 78294x); U.S. Pat., 3402241, 1968 (Chem. Abstr., 1968, 68, 95830m). 5 M. Baues, V. Kraatz and F. Korte, Liebigs Ann. Chem., 1973, 1310. 6 N. Cromwell and K. Tsuo, J. Am. Chem. Soc., 1949, 71, 993. 7 J. Lutz, J. Freek and R. Murphy, J. Am. Chem. Soc., 1972, 94, 8722. 8 S. Yakimovich and V. Nikolaev, Zh. Org. Khim., 1981, 17, 1104. 9 R. Lutz and R. Jordan, J. Am. Chem. Soc., 1949, 71, 996. 10 Ph. Weintkaub, D. Meyer and Ch. Aiman, J. Org. Chem., 1980, 45, 4989. 11 S. Yakimovich and V. Nikolaev, Zh. Org. Khim., 1982, 18, 1173. 12 P. Vainiotalo, P. Savilainen, M. Ahlgrien, P. J. Malkonen and J. Vepsalainen, J. Chem. Soc., Perkin Trans. 2, 1991,

ISSN:0308-2342    

DOI:10.1039/a702638b

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

O CO2Me CO2Me CO2Me O OH IBD–KOH MeOH H2O PhI O CO2Me R a R = H b R = Me 1 PhI CO2Me O 5 2 3 4 2–4 a R = H; b R = Me HCl (a) (b) O CO2Me O CO2Me O CO2Me IBD–KOH MeOH IBD–KOH MeOH OMe OMe 6 7 8 OH OMe OMe R R R OMe O CO2Me 6 OTs 10 HTIB CH2Cl2 O CO2Me 9 2a HTIB CH2Cl2 (a) (b) OTs CO2Me O– 2a –OMe IBD–KOH MeOH CO2Me O I Ph OMe 11 –OMe O OMe CO2Me 12 –OMe 3a PhI(OMe)2 32 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 32–33† Functionalization of Fused Cyclopentane Derivatives using Hypervalent Iodine Reagents† Robert M.Moriarty,* Neena Rani, Eric J. May, Liang Guo and Om Prakash*‡ Department of Chemistry, University of Illinois at Chicago, 845 West Taylor St., Chicago, IL 60607, USA Fused cyclopentane derivatives, viz. methyl 2-oxobicyclo[3.1.0]hexane-1-carboxylate (2a), methyl 6-methyl- 2-oxobicyclo[3.1.0]hexane-1-carboxylate (2b) and methyl 3-oxotricyclo[3.3.0.02,8]octane-2-carboxylate (6), have been functionalized by using the hypervalent iodine reagents iodobenzene diacetate (IBD) and [hydroxy(tosyloxy)iodo]benzene (HTIB).Considerable attention has been devoted to the development of methods for the synthesis and functionalization of fused cyclopentane derivatives because of the presence of this ring system in a large number of biologically active natural products.1,2 As part of our programme on the synthetic utility of hypervalent iodine reagents, we have earlier reported a useful approach for intramolecular cyclopropanation.3,4 This methodology, involving copper(I)-catalysed decomposition of iodonium ylides, has led to the synthesis of various bicyclic and tricyclic compounds containing a cyclopentane ring.In this paper we describe the application of hypervalent iodine reagents to the functionalization of fused bi- and tricyclopentane derivatives, viz. methyl 2-oxobicyclo[3.1.0]hexane- 1-carboxylate (2a), methyl 6-methyl-2-oxobicyclo[3.1.0]hexane- 1-carboxylate (2b) and methyl 3-oxotricyclo[3.3.0.02,8]- octane-2-carboxylate (6).The cyclic oxo esters 2a, 2b and 6, synthesized by copper( I)-catalysed intramolecular cyclization of the respective iodonium ylides 1a, 1b and 5,3 were first subjected to oxidation with iodobenzene diacetate (IBD) in methanolic potassium hydroxide. This system (IBD–KOH/MeOH) is employed to introduce a hydroxy group at the a-position of an enolizable ketone via a-hydroxy dimethyl acetal formation. 5 In the present study, oxidation of bicyclic ketones 2a and 2b with IBD (1 mol equivalent) in KOH–MeOH afforded the normal a-hydroxy dimethyl acetals 3a and 3b, but no indication of the formation of such a product was observed in the oxidation of the tricyclic ketone 6 (Scheme 1a).Instead, this reaction led to the formation of the a,a-dimethoxy ketone 8 in about 35% yield (Scheme 1b). The formation of product 8 occurs via the intermediate 7. As expected, treatment of 6 with 2 mol equivalents of IBD gave 8 in optimum yield (77%).Keeping in mind that methyl 3-hydroxy-2-oxobicyclo- [3.1.0]hexane-1-carboxylate (4a) could be used as a ring A synthon in vitamin D synthesis,6 it was considered worthwhile to hydrolyse the acetals 3a and 3b to 4a and 4b respectively. Thus, 3a and 3b were treated with dilute hydrochloric acid to obtain the corresponding a-hydroxyketones (4a and 4b). We then turned our attention to effecting a-tosyloxylation of the ketones 2a and 6 with [hydroxy(tosyloxy)iodo]benzene (HTIB, Koser’s reagent).The method of Koser et al.7,8 successfully transformed these ketones into the corresponding a-tosyloxy ketones 9 and 10 (Scheme 2a and b). The observed difference in the reactivity pattern of the bicyclic and tricyclic ketones towards IBD–KOH/MeOH may be rationalized on the basis of steric factors involved in the mechanistic pathway. The first step in the iodine(III)- mediated a-hydroxy dimethyl acetal formation is the creation of an electrophilic centre a to the carbonyl group by addition of the hypervalent iodine species PhI(OMe)2 [generated from IBD–KOH/MeOH] to give an IIII intermediate (e.g., 11 from 2a).The fate of this intermediate is controlled both by the reaction conditions as well as its chemical structure. In the presence of KOH–MeOH, formation of an a-hydroxy dimethyl acetal occurs by nucleophilic attack of methoxide ion in two steps: initial attack of µOMe at the carbonyl group gives epoxide 12, which subsequently undergoes ring opening by the second attack of µOMe to yield the product (3a starting from 2a; Scheme 3).The tricyclic ketone 6 does not follow the normal pathway, presumably because of the steric hindrance associated with *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). ‡On leave of absence from Kurukshetra University, India.Scheme 1 Scheme 2 Scheme 3OMe CO2Me 13 O CO2Me 14 OH OMe OMe J. CHEM. RESEARCH (S), 1998 33 the epoxide 13 which is prerequisite for the formation of the desired a-hydroxy dimethyl acetal 14.5 In this case the IIII intermediate (analogous to 11) undergoes nucleophilic substitution by methoxide ion followed by further oxidation of the resultant a-methoxy ketone 7 to yield the a,a-dimethoxy ketone 8. The formation of the a-toxyloxy ketones 9 and 10 occurs according to the general pathway for a-tosyloxylation of ketones.7,8 Finally, noteworthy features of this study are: (i) several new a-functionalized ketones containing bicyclo[3.1.0]hexane and tricyclo[3.3.0.02,8]octane systems are easily accessible; (ii) reaction conditions employed for these a-functionalizations do not affect the cyclopropane system of the ketones 2a, 2b or 6; (iii) it is demonstrated that hypervalent oxidative a-hydroxylation of ketones using IBD–KOH/MeOH is applicable to the [3.1.0]bicyclic ketones 2a and 2b, but that the ketone 6, which contains the tricyclo[3.3.0.02.8]octane system, leads to an a,a-dimethoxylated ketone; and (iv) the HTIB-induced method works successfully to introduce a tosyloxy group at the a-position for both bicyclic and tricyclic ketones.Experimental Mps and bps are uncorrected. Silica gel (230–400 mesh) was used for column chromatography. The cyclic ketones 2a, 2b and 6 were prepared according to our previous method involving copper(I)-catalysed decomposition of the corresponding iodonium ylides 1a, 1b and 5, which in turn were prepared from the reaction of appropriate b-oxo esters with IBD– KOH/MeOH.3 Conversion of Methyl 2-Oxobicyclo[3.1.0]hexane-1-carboxylate (2a) into Methyl 3-Hydroxy-2-oxobicyclo[3.1.0]hexane-1-carboxylate (4a).·Step 1.Methyl 3-hydroxy-2,2-dimethoxybicyclo[3.1.0]hexane- 1-carboxylate (3a). To a stirred solution of potassium hydroxide (1.68 g, 30 mmol) in methanol (40 ml) at 0 °C was added a solution of the ketone 2a (1.54 g, 10 mmol) in methanol (10 ml) over 10 min.The solution was stirred for another 10 min and then iodobenzene diacetate (3.54 g, 11 mmol) was added in three portions over 10 min. The resulting homogenous mixture was stirred for 2 h at 0 °C and then for 2 h at room temperature, concentrated in vacuo, diluted with water (40 ml) and extracted with dichloromethane (3Å50 ml).The combined organic extracts were dried (MgSO4) and concentrated in vacuo to remove solvent and iodobenzene. The crude hydroxy dimethyl acetal 3a (1.60 g), obtained as an oil [vmax/cmµ1 (neat) 3505, 1725; dH (400 MHz, CDCl3) 1.35 (m, 1 H), 1.48 (t, J 5.5 Hz, 1 H), 1.76 (d, J 14 Hz, 1 H), 2.07 (m, 1 H), 2.24 (m, 1 H), 3.29 (s, 3 H), 3.59 (s, 3 H), 3.62 (s, 3 H), 4.01 (d, J 7.0 Hz, 1 H). dC (100 MHz, CDCl3) 16.87, 26.88, 31.84, 34.454, 59.26, 51.39, 53.04, 73.43, 108.21, 171.10; m/z (CI) 217 (M+1, 1.4%), 199 (3), 185 (51), 1543 (100)], was used as such for the next step.Step 2. Methyl 3-hydroxy-2-oxobicyclo[3.1.0]hexane-1-carboxylate (4a). To a solution of the crude dimethyl acetal 3a (1.5 g) in methanol (10 ml) was added 2 M HCl (10 ml) and the homogeneous mixture was allowed to stir at room temperature for 3 h. Methanol was removed in vacuo and the aqueous mixture was extracted with dichloromethane (4Å25 ml). The combined organic extracts were dried (MgSO4) and concentrated in vacuo and the resulting residual mass was purified by flash column chromatography on silica gel eluting with hexanes–diethyl ether (1:1 v/v) to give 0.5 g (42%) of 4a as an oil, v,max/cmµ1 (neat) 3463, 1757, 1722; dH (300 MHz, CDCl3) 0.84 (d, J 5.5 Hz, 1 H), 1.69–1.74 (m, 1 H), 2.16–2.22 (m, 1 H), 2.40 (d, J 18 Hz, 1 H), 2.78 (d, J 2.7 Hz, 1 H), 2.83–2.91 (m, 1 H), 3.76 (s, 3 H), 5.01 (s, 1 H); dC (75.43 MHz, CDCl3) 17.87, 21.28, 30.90, 38.38, 52.37, 75.02, 172.70, 211.82; m/z (CI) 171 (M+1, 31%), 153 (100), 139 (22) (Found: C, 55.86; H, 5.99.C8H10O4 requires C, 56.47; H, 5.88%). Conversion of 2b into 4b was also effected according to the above method. 3b: oil; yield 51%; vmax/cmµ1 (neat) 3521, 1732; dH (300 MHz, CDCl3) 1.03 (d, J 6.3 Hz, 3 H), 1.33–1.48 (m, 2 H), 1.64 (t, 1 H), 2.32–2.43 (m, 1 H), 2.62 (br d, 1 H), 3.27 (s, 3 H), 3.53 (s, 3 H), 3.67 (s, 3 H), 4.10 (m, 1 H); dC (75.43 MHz, CDCl3) 13.37, 25.35, 28.20, 29.59, 33.69, 42.46, 49.99, 51.57, 51.77, 76.98, 107.60; m/z (CI) 231 (M+1, 11%), 213 (23), 199 (30), 185 (74), 167 (90), 153 (100), 135 (45) (Found: C, 58.13; H, 7.50.C11H18O5 requires C, 57.39; H, 7.83%). 4b: oil; vmax/cmµ1 (neat) 1754, 1723; dH (300 MHz, CDCl3) 1.18–1.23 (m, 1 H), 1.31 (d, J 6.0 Hz, 3 H), 2.05 (t, J 5.4 Hz, 1 H), 2.42 (d, J 18 Hz, 1 H), 2.76–2.88 (m, 2 H), 3.79 (s, 3 H, 4.83 (s, 1 H); dC (75.43 MHz, CDCl3) 11.45, 26.59, 27.14, 35.67, 38.65, 52.16, 75.80, 171.46, 212.16; m/z (CI) (M+1, 54%), 167 (100), 153 (58), 135 (26) (Found: C, 58.48; H, 6.74.C9H12O4 requries C, 58.70; H, 6.52%). Methyl 4,4-Dimethoxy-3-oxotricyclo[3.3.0.02,8]octane-2-carboxylate (8).·A solution of the ketone 6 (1.8 g, 10 mmol) in methanol (5 ml) was treated with KOH (3.36 g, 60 mmol) in methanol (50 ml) followed by IBD (6.44 g, 20 mmol) according to the procedure described for the conversion of 2 into 3. The crude product was purified by flash column chromatography on silica gel, eluting with hexanes–diethyl ether (1:1) to give 1.74 g (77%) of 8 as an oil, vmax/ cmµ1 (neat) 1733, 1717; dH (300 MHz, CDCl3) 1.80–2.04 (m, 3 H), 2.18–2.34 (m, 2 H), 2.74–2.79 (m, 1 H), 2.85–2.92 (m, 1 H), 3.44 (s, 3 H), 3.57 (s, 3 H), 3.68 (s, 3 H); dC 22.93, 31.36, 33.03, 39.93, 40.29, 49.47, 50.40, 51.99, 52.82, 100.39, 169.20, 211.94; m/z (CI) 241 (M+1, 15%), 223 (30), 209 (100) (Found: C, 59.61; H, 6.62; C12H16O5 requires C, 60.00; H, 6.67%).Procedure for the a-Tosyloxylation of 2 and 6.·To a stirred solution of the ketone (10 mmol) in dichloromethane (30 ml) was added [hydroxy(tosyloxy)iodo]benzene (7.84 g, 20 mmol) and the mixture was refluxed overnight.The solvent was removed in vacuo and the residue was chromatographed on silica gel to give the a-tosyloxy ketone as a colourless crystalline solid which was recrystallized from the appropriate solvent. Methyl 2-oxo-3-tosyloxybicyclo[ 3.1.0]hexane-1-carboxylate (9), yield 65%, had mp 118–119 °C; vmax/cmµ1 (KBr) 1765, 1720, 1372, 1177; dH (400 MHz, CDCl3) 1.62 (t, J 5.4 Hz, 1 H), 2.08 (dd, J1 2.6 Hz, J2 15.1 Hz, 1 H), 2.13 (m, 1 H), 2.40 (s, 3 H), 2.50 (m, 1 H), 2.61 (m, 1 H), 3.67 (s, 3 H), 4.65 (dd, J1 2.6 Hz, J2 9.7 Hz, 1 H), 7.33 (d, J 8.1 Hz, 2 H), 7.75 (d, J 8.1 Hz, 2 H); dC (100 MHz, CDCl3) 21.66, 23.67, 29.45, 29.56, 36.79, 52.53, 78.08, 128.08, 129.92, 132.85, 145.33, 167.80, 197.37; m/z (CI) 325 (M+1, 100%), 293 (39), 169 (17), 155 (49), 153 (94) (Found: C, 55.48; H, 4.95; S, 9.87.C15H16O6S requires C, 55.56; H, 4.94; S, 9.88). Methyl 3-oxo-4-tosyloxybicyclo[3.1.0.02,8]octane-2-carboxylate (10), yield 75%, had mp 158–160 °C; vmax/cmµ1 (KBr) 1738, 1711, 1368, 1179; dH (400 MHz, CDCl3) 1.85 (m, 1 H), 2.10–2.20 (m, 3 H), 2.38 (m, 1 H), 2.49 (s, 3 H), 2.68 (d, 1 H), 2.98 (dd, J1 4.3 Hz, J2 7.7 Hz, 1 H), 3.75 (s, 3 H), 5.08 (t, J 5.0 Hz, 1 H), 7.38 (d, J 8.3 Hz, 2 H), 7.80 (d, J 8.3 Hz, 2 H); dC (100 MHz, CDCl3) 15.47, 21.66; 24.04, 37.47, 38.93, 44.26, 45.66, 52.49, 73.91, 127.80, 130.14, 133.33, 145.44, 166.63, 200.53; m/z (CI) 351 (M+1, 79%), 319 (8), 179 (100) (Found: C, 57.89; H, 5.16; S, 8.84.C17H18O6S requires C, 58.29; H, 5.14; S, 9.14). We are thankful to the National Science Foundation for the financial support of this work (Grant No. CHE- 95230157). Received, 28th February 1997; Accepted, 18th September 1997 Paper E/7/01440F References 1 L. A. Paquette, Top. Curr. Chem., 1979. 40, 41. 2 O. Sticher, in New Natural Products and Plant Drugs with Pharmacological, Biological or Therapeutical Activity, ed. H. Wagner and P. Wolff, Springer, Berlin and New York, 1977, p. 137. 3 R. M. Moriarty, O. Prakash, R. K. Vaid and L. Zhao, J. Am. Chem. Soc., 1989, 111, 6443. 4 R. M. Moriarty, J. Kim and L. Guo, Tetrahedron Lett., 1993, 34, 4129. 5 For review articles see: R. M. Moriarty and O. Prakash, Acc. Chem. Res., 1986, 19, 244; O. Prakash, N. Saini, M. P. Tanwar and R. M. Moriarty, Contemp. Org. Synth., 1995, 2, 121. 6 H. Nemoto, X.-M. Wu, H. Kurobe, M. Ihara and K. Fukumoto, Tetrahedron Lett., 1983, 24, 4257; H. Nemoto, X.-M. Wu, H. Kurobe, M. Ihara, K. Fukumoto and T. Kameleni, Tetrahedron Lett., 1984, 25, 3095. 7 G. F. Koser, A. G. Relenyi, A. N. Kalos, L. Rebrovic and R. H. Wettach, J. Org. Chem., 1982, 47., 2487. 8 For a review, see R. Moriarty, R. K. Vaid and G. F. Koser, Synlett, 1990, 365.

ISSN:0308-2342    

DOI:10.1039/a701440f

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

O CH2OH N R CH2 Ph R¢ H + O CH2OH H R¢ N CH2 Ph R heat O CH2OH N H R3 R1 R2 1 1 O CH2OH N R1 R2 R3 + H a R1 = R2 = CH2Ph, R3 = Bun b R1 = R2 = CH2Ph, R3 = [CH2]3OCH2Ph c R1 = H, R2 = CH2Ph, R3 = Bun d R1 = H, R2 = CH2 OMe, R3 = [CH2]3OCH2Ph d R1 = H, R2 = CH2 OMe, R3 = Bun 2 34 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 34–35† Thermolysis Improvements in Retro-Diels–Alder Reactions of Benzylamino Alcohols under Microwave Irradiation† Michel Bortolussi,* Robert Bloch and Andr�e Loupy R�eactivit�e et Synth`ese S�elective (UA CNRS 478), I.C.M.O., B�at. 420, Universit�e de Paris-Sud, 91405 Orsay, France Microwave activation under solvent-free conditions is shown to be the best procedure for performing retro-Diels–Alder reactions. Retro Diels–Alder reactions often require drastic conditions, high temperatures and even sometimes flash vacuum thermolysis (FVT).1–4 Such thermolytic procedures have been used to prepare unsaturated amino alcohols from a variety of amino alcohols (Scheme 1).In the case of dibenzylamino alcohols (R=PhCH2), satisfactory yields are obtained by refluxing in xylene solution for rather long times (6 h). However, these conditions prove unsuccessful in the case of monobenzylamino compounds (R=H) where only a solvent-free method (heating of the neat product for 6 h at 160 °C) leads to a mostly clean reaction. Owing to the lack of volatility of these compounds, FVT is not useful in this case, since decomposition occurs before evaporation in the hot tube.A dry technique, coupled with microwave activation, has been advocated in the case of hightemperature transformations6,7 and for the displacement of volatile polar molecules.8 Several reactions were therefore performed under microwave irradiation for a variety of neat liquid adducts 1 using a single mode reactor (Synthewave 402 apparatus from Prolabo) in order to control precisely the experimental conditions (power and temperature).To check the possible specific effects (non-thermal) of microwaves, the results were compared with those obtained under conventional heating in a thermostatted oil bath, conditions elsewhere being equal. Yields were quantitative for all five desired products within very short times (10 or 15 min) and at relatively low temperatures (120–140 °C). A very important specific effect of microwaves is clearly exemplified, as on conventional heating under strictly otherwise identical conditions yields were less than 2%.Under classical thermal conditions, reaction times of 6–10 h were necessary to obtain acceptable yields (however always lower than under microwaves) of less pure products. The specific effect of microwaves is here very important, although not always obvious under homogeneous conditions.10 It is interesting to note that such an intrinsic effect of microwaves occurs in the most difficult cases yet observed for other types of solvent-free reactions.11 Such an observation is coherent with a remark of Lewis12 who underlined a generalization which has recently become obvious, stating that the more important microwave effects are connected to the more difficult reactions.Microwave activation coupled with solvent-free conditions is shown to be by far the most efficient method for performing these retro Diels–Alder reactions. The improvements are remarkable if we consider that both classical thermolysis and FVT (leading to decomposition) are poorly productive (or non-operative).Especially for monobenzylated amino compounds 1c–e, solvent-free conditions plus microwave irradiation constitute the only method of giving fast and clean reactions. Experimental Focused microwave irradiations were carried out with a Synthewave S402 single mode reactor from Prolabo (2450 MHz, 300 W) with irradiation monitoring by PC, infrared9 measurement and continual feedback temperature control. Indicated temperatures *To receive any correspondence (e-mail: mbortolu@icmo.upsud.fr). †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 Microwave-assisted thermolysis of neat benzylamino alcohols 1a–e Microwave activation Classical heating Time Yield (%)a Time Substrate T/°C (t/min) of 2 T/°C (t/min) Yield (%)a 1a 1b 1c 1d 1e 120 140 140 120 120 100 120 15 10 10 15 15 15 15 66 E98 E98 E98 E98 E65 E98 140 140 160 120 120 180 480 360 180 600 70 84 74 50 84 aIsolated yield of pure product.Scheme 1 Scheme 2J. CHEM. RESEARCH (S), 1998 35 were reached in less than 1 min and maintained by power regulation. For sake of comparison, reactions were also conducted under classical heating in a thermostatted oil-bath. Neat amino alcohols 1a–e (10 mmol)5 were placed in a Pyrex open flask allowing the removal of furan.After microwave irradiation or conventional heating, the products were removed with methylene dichloride and analysed by 1H NMR spectroscopy. Unsaturated amino alcohols 2 obtained under microwaves were highly pure and did not need further purification. Products 2a–e showed similarities in their 1H NMR spectra: in particular the values of the coupling constants between the vicinal ethylenic protons (J110 Hz) were characteristic of Z-olefins. For example, the full 1H NMR spectrum of compound 2a was the following: dH (CDCl3, 250 MHz) 0.89 (t, J 6.5 Hz, 3 H), 1.23–1.44 (m, 5 H), 1.77–1.85 (m, 1 H), 2.40 (bs, 1 H), 3.37 (dt, J 8.5, 6.1 Hz, 1 H), 3.5 (d, J 13.6 Hz, 2 H), 3.73 (d, J 13.6 Hz, 2 H), 3.9 (ddd, J 6.5, 5, 1 Hz, 1 H), 3.93 (ddd, J 6.5, 6, 1 Hz), 5.57 (ddt, J 9.8, 9.5, 1 Hz, 1 H), 5.91 (ddt, J 9.8, 6.6, 1 Hz, 1 H), 7.21–7.40 (m, 10 H).Received, 26th June 1997; Accepted, 16th September 1997 Paper F/7/06839E References 1 J. L. Ripoll, A. Rouessac and F. Rouessac, Tetrahedron, 1978, 34, 19. 2 M. C. Lasne and J. L. Ripoll, Synthesis, 1985, 121. 3 A. Ichihara, Synthesis, 1987, 207. 4 C. Cinquin, M. Bortolussi and R. Bloch, Tetrahedron, 1996, 52, 6943. 5 M. Bortolussi, C. Cinquin and R. Bloch, Tetrahedron Lett., 1996, 37, 8729. 6 A. Loupy, G. Bram and J. Sansoulet, New J. Chem., 1992, 16, 233. 7 S. Caddick, Tetrahedron, 1995, 51, 10403. 8 A. Loupy, A. Petit, M. Ramdani, C. Yvanaeff, M. Majdoub, B. Labiad and D. Villemin, Can. J. Chem., 1993, 71, 90. 9 P. Jacquault, Eur. Pat., 92-420477.9, 1992. 10 R. Laurent, A. Laporterie, J. Dubac, J. Berlan, S. Lefeuvre and M. Audhuy, J. Org. Chem., 1992, 57, 7099. 11 A. Loupy, P. Pigeon and M. Ramdani, Tetrahedron, 1996, 52, 6705 and references cited therein. 12 D. A. Lewis, Mater. Res. Soc. Symp. Proc., 19

ISSN:0308-2342    

DOI:10.1039/a706839e

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

OAc H H O H O H H (–)-1 (–)-2 3 C O CH2Cl CHO H CHO H H 4 5 6 CHO CHO OH OH 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 i ii H 6 OH OH 1 2 3 4 5 6 7 8 9 10 11 12 15 i H 7 OH OH O OH H 8 OH OH OH ii iii H O R H O H OH H OAc vi v iv 10 (–)-2 9 R = a-CH2OH 11 R = b-CH2OH (–)-1 36 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 36–37† Partial Synthesis of (µ)-11,12-Dinordriman-8-one and the (µ)-Enantiomer of Polywood† Manuel Cort�es,* Luis Moreno and Jos�e L�opez Facultad de Qu�ýmica, Pontifica Universidad Cat�olica de Chile, Casilla 306, Correo 22, Santiago, Chile A chiral sequiterpene diol 6, readily available from the natural product polygodial (4), has been used for the first partial synthesis of the title compounds.In a study of the odour evaluation of trans-decalins, the secondary acetate (�)-1 and the ketone (�)-2 have been reported to possess a woody tonality.1,2 Racemic 1 (known as Polywood) and 2 have been previously synthesized by acid-catalysed cyclization of acyclic or monocyclic precursors.3,4 Later, the acetate (µ)-1 and ketone (µ)-2 were prepared using enzyme-catalysed kinetic resolution of (�)-3.5 Pursuing our interest in the synthesis of terpenoids and related products from naturally chiral compounds, 6–8 we report here the first partial syntheses of (µ)-1 and (µ)-2, using readily available starting material and cheap reagents.The starting material was the chiral diol 69–10 derived from isopolygodial (5) which in turn was obtained by basic isomerization of polygodial (4), available from various natural sources11–13 (Scheme 1).The synthetic sequence is shown in Scheme 2. Epoxidation of 6 with m-chloroperbenzoic acid produced a single epoxide (7) in 75% yield. the a-stereochemistry of the epoxide was determined by means of both 1H and 13C NMR spectroscopy. Comparison of the 7-H signal in the 1H NMR spectrum of 7 (d 3.3, dd, W1/2 5.2 Hz) with that of 11-acetoxy- 7a,8-epoxydrimane (d 3.04, dd, W1/2 4.6 Hz)14 indicated that both compounds have the same epoxide stereochemistry. On the other hand the signal for C-5, appearing at a field of 15.2 ppm higher than that corresponding to 6 in the 13C NMR spectrum, confirmed the a configuration of the epoxide as reported for similar compounds.15 This stereochemistry is explained by considering that the hydrogen bonding between the hydroxy group at C-11 and the peracid directs the epoxidation reactions.16 The epoxide 7 was refluxed with LiAlH4 in tetrahydrofuran (THF) to afford the triol 8 in 85% yield.Oxidative degradation of 8 with sodium periodate gave the ketol 9 in 75% yield. Transformation of 9 into (µ)-2 was carried out by treatment with Jones reagent. The carboxylic acid could not be isolated because decarboxylation was spontaneous. The retro-aldol process was discarded because when the ketol 9 was treated with a mixture of sulfuric acid, water and acetone (Jones reagent without CrO3), the starting material was recovered exclusively.The physical constants and spectral data of (µ)-2 were in accord with the values described by Gautier et al.5 Compound (µ)-2 was reduced with DIBALH to give the b-alcohol 10 in 80% yield. Finally, acetylation of 10 with Ac2O in pyridine gave (µ)-1 in 97% yield. It is important to note that attempted oxidation of the epimeric ketol 11 (prepared by the same sequence starting with the diol derived from polygodial) gave a large number of products, none of which could be identified. We have no explanation for the difference in reactivity between the two epimers. Experimental Melting points were determined on a Kofler hot-stage apparatus and are uncorrected.Optical rotations were obtained for solutions in chloroform (g/100 mL) on a Perkin Elmer 241 polarimeter. 1H and 13C NMR spectra were recorded on a Bruker AM 200 spectrometer. Chemical shifts are reported in ppm downfield relative to tetramethylsilane (d scale) in CDCl3 solutions.Carbon substitution degrees were established by DEPT pulse sequence. For analytical TLC, Merck silica gel 60G in 0.25 mm thick layers was used. Chromatographic separations were carried out by conventional column on Merck silica gel 60 (70–230 mesh) using hexane– EtOAc mixtures of increasing polarity. All organic extracts were dried over anhydrous sodium sulfate and evaporated under reduced pressure, below 65 °C. (µ)-Polygodial (4) was purified from a light petroleum extract of the bark of Drimys winteri.11 7a,8-epoxy-(9b-H)-drimane-11,12-diol (7).·To a solution of the diol 6 (1 g, 4.2 mmol) in CH2Cl2 (30 mL) m-chloroperbenzoic acid *To receive any correspondence (e-mail: rmeza@lascar.puc.cl).†This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Scheme 1 Reagents: i, KOH, MeOH (50%); ii, NaBH4, MeOH (80%) Scheme 2 Reagents: i, m-chloroperbenzoic acid, CH2Cl2, 15 °C (75%); ii, LiAlH4, THF (85%); iii, NaIO4, MeOH (75%); iv, CrO3, H2SO4, acetone (72%); v, DIBALH, THF (80%); vi, Ac2O, Py (97%)1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 J.CHEM. RESEARCH (S), 1998 37 (0.94 g, 5.4 mmol) was added in small portions at room temperature during 10 min. Stirring was continued at room temperature for 35 min. The reaction mixture was washed with NaHCO3 and water, dried and concentrated.The residue was chromatographed over silica gel to afford the (unstable) epoxide 7 (0.79 g, 75%), mp 105–107 °C (from acetone–hexane); [a]D 25 µ69.2 (1.01, CHCl3) dH 0.84 (s, 3 H), 0.87 (s, 3 H), 0.94 (s, 3 H) and 3.3 (dd, W1/2 5.2 Hz) (Found: C, 69.90; H, 10.60. C15H26O3 requires C, 70.83; H, 10.30%). (8R)-(9b-H)-Drimane-8,11,12-triol (8).·To a stirred mixture of LiAlH4 (0.6 g, 16 mmol) in dry THF (50 mL) a solution of the epoxide 7 (1.15 g, 4.5 mmol) in dry THF (30 mL) was added and the mixture was heated at reflux temperature under nitrogen for 4 h.The excess of reagent was decomposed by the addition of EtOAc and an aqueous solution of HCl (10%). The mixture was extracted with EtOAc and the organic phase was washed with NaHCO3 and water, dried and concentrated to give the triol 8 (0.99 g, 85%) mp 117–120 °C (from EtOAc); [a]D 25 µ41.6 (c, 1.12), dH 0.75 (s, 3 H), 0.82 (s, 3 H) 1.01 (s, 3 H) and 3.5–4.0 (m, 4 H) (Found: C, 69.90; H, 11.09.C15H28O3 requires C, 70.27; H, 11.01%). 11-Hydroxy-(9b-H)-12-nordriman-8-one (9).·To a stirred solution of NaIO4 (0.76 g, 3.53 mmol) in water (15 mL) a solution of the triol 8 (0.86 g, 2.54 mmol) in MeOH (10 mL) was added at room temperature during 1.5 h. The reaction solution was extracted with EtOAc and the organic phase was washed with NaHCO3, water and dried. The crude product was purified by column chromatography to provide compound 9 (0.5 g, 75%), mp 111–112 °C (from acetone–hexane); [a]D 25 µ22.1 (c, 0.68 in CHCl3); dH 0.92 (s, 3 H), 0.94 (s, 3 H), 0.94 (s, 3 H), 2.1–2.4 (m, 2 H) and 3.93 (m, 2 H) (Found: C, 74.80; H, 10.80.C14H24O2 requires C, 74.95; H, 10.78%). 11,12-Dinordriman-8-one [(µ)-2].·To compound 9 (3.2 g, 15.4 mmol) in acetone (50 mL) Jones reagent (11.5 mL, 2.6 M; 30.8 mmol) was added while swirling and the reaction was monitored by TLC. Usual work-up gave the ketone (µ)-2 (2.2 g, 72%), mp 90–92 °C (from hexane) (lit.,5 88–90 °C); [a]D 25 µ81.8 (c, 1.1 in CHCL3) {lit.,5 [a]20 D µ81.6 (c, 1.23 in CHCl3)}.For spectroscopic data see ref. 5. 11,12-Dinordriman-8b-ol (10).·To a solution of the ketone (µ)-2 (0.5 g, 0.52 mmol) in dry THF (20 ml) at 0.1 M solution of diisobutylaluminium hydride in hexane (5 mL, 5 mmol) was added dropwise at room temperature. The reaction mixture was stirred for 2 h at room temperature. EtOAc (5 mL) and water (5 mL) were then successively added and the organic phase was separated.The aqueous layer was extracted with EtOAc. The combined organic phases were washed with brine, dried and concentrated. The residue was purified bography to afford the b-alcohol 10 (0.43 g, 80%), mp 89–91 °C (from hexane) (lit.,5 89–90 °C), [a]D 25 µ18.8 (c, 0.32 in CHCl3) [lit.,5 µ19.6 (c, 1.2 in CHCl3)]. For spectral data, see ref. 5. 8b-Acetoxy-11,12-dinordrimane (µ)-2 (Polywood).·Acetylation of 10 (0.06 g, 0.31 mmol) under normal conditions with Ac2O– pyridine gave the acetate (µ)-1 (0.07 g, 97%) as an oily product; [a]D 25µ15.60 (c, 0.52 in CHCl3) (lit.,5 [a]D 20µ16.47).The 1H and 13C NMR spectra were in accord with those kindly sent to us by Dr N�af (ref. 5). We gratefully acknowledge the Consejo Nacional de Ciencia y Tecnolog�ýa (Research Grant 1960451) for financial support. We also thank Dr F. N�af (Firmenich SA, Research Lab. Switzerland) for 1H and 13C NMR spectra of compounds (µ)-2 and (µ)-1 and Professor S.Alegr�ýa for helpful discussions. Received, 22nd April 1997; Accepted, 29th September 1997 Paper E/7/02743E References 1 G. Ohloff, The Fragrance of Ambergris, in Fragrance Chemistry, ed. E. T. Theimer, Academic Press, New York, 1982, p. 553. 2 G. Ohloff, Experientia, 1986, 42, 271. 3 G. Ohloff, F. N�af, R. Decorzant, W. Thommen and E. Sundt, Helv. Chim. Acta, 1973, 56, 1414. 4 S. M. Linder, D. Reichlin and R. L. Snowden, Tetrahedron Lett., 1993, 34, 4789. 5 A. Gautier, C. Vial, C. Morel, M. Lander and N. N�af, Helv. Chim. Acta, 1987, 70, 2039. 6 M. Cort�es and J. L�opez, Nat. Prod. Lett., 1994, 5, 183. 7 V. Armstrong, M. Cort�es and J. L�opez, Nat. Prod. Lett., 1996, 8, 225. 8 M. E. Reyes, V. Armstrong, E. Madriaga, M. Cort�es and J. L�opez, Synth. Commun., 1996, 26, 1995. 9 A. J. Aasen, T. Nishida, C. R. Enzell and H. Appel, Acta Chem. Scand., Ser. B, 1997, 31, 51. 10 G. Aranda, I. Facon, J. I. Lallemand, M. Leclaire, R. Azerad, M.Cort�es, J. L�opez and H. Ramirez, Tetrahedron. Lett., 1992, 51, 7845. 11 M. Cort�es and M. L. Oyarz�un, Fitoterapia, 1981, 52, 33. 12 C. S. Barnes and J. W. Loder, Aust. J. Chem., 1962, 15, 322. 13 Y. Fukuyama, T. Sato, Y. Asakawa and T. Takemoto, Phytochemistry, 1982, 21, 2895. 14 D. M. X. Donelly, J. O’Reilly, A. Chiaroni and J. Polonsky, J. Chem. Soc., Perkin Trans 1, 1980, 2196. 15 M. G. Sierra, M. I. Colombo, M. E. Zudenigo and E. A. Ruveda, Phytochemistry, 1984, 23, 1685. 16 M. Mousseron-Canet, B. Labeeuw and J. C. Lane, Bull. Soc. Chim. Fr., 1968, 2125. Table 1 13C NMR data (CDCl3, 50.3 MHz) Compound Carbon 6 7 8 9 (µ)-2 10 (µ)-1 C-1 C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-11 C-12 C-13 C-14 C-15 COCH3 COCH3 36.5 18.8 42.7 33.1 54.1 24.3 127.5 137.2 43.3 36.0 63.1 67.7 21.7 22.0 33.0 36.3 18.3 42.4 32.8 38.9 22.8 56.9 61.9 48.4 34.8 60.3 66.7 22.1 22.8 32.9 37.4 20.1 42.2 33.4 56.7 18.8 33.1 76.5 48.5 37.6 60.9 69.4 21.8 23.7 33.1 39.3 18.5 42.2 33.4 46.0 23.2 36.8 214.7 67.1 40.0 60.7 · 22.0 22.0 33.5 42.0 18.8 42.3 33.2 52.2 23.1 42.0 211.7 59.6 38.4 —— 19.4 21.4 33.3 42.4 18.3 42.5 33.0 54.3 17.0 35.2 67.9 51.3 34.2 —— 21.4 21.4 33.1 42.1 18.3 42.4 33.0 53.9 17.6 32.2 70.6 47.8 34.2 —&

ISSN:0308-2342    

DOI:10.1039/a702743e

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

R OH + O CO2Et R O O Me K-10 or KSF toluene, reflux 0-96 % 1 2 38 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 38–39† Montmorillonite Clay Catalysis. Part 7.1 An Environmentally Friendly Procedure for the Synthesis of Coumarins via Pechmann Condensation of Phenols with Ethyl Acetoacetate† Tong-Shuang Li,* Zhan-Hui Zhang, Feng Yang and Cheng-Guang Fu Department of Chemistry, Hebei University, Baoding 071102, Hebei Province, P.R. China Coumarins are synthesised via Pechmann condensation of phenols with ethyl acetoacetate catalysed by montmorillonite clay in satisfactory yields; the scope and limitation of the method have been investigated.Coumarins occupy a special place in the realm of natural and synthetic organic chemistry because many products which contain this subunit exhibit useful and diverse biological activity such as molluscacides,2 have anthelmintic, hypnotic and insecticidal properties,3 or serve as anticoagulant agents4 or fluorescent brighteners.5 These compounds can also be used for the synthesis of other products such as furocoumarins, chromenes, coumarones and 2-acylresorcinols.6 There have been many synthetic routes to the coumarins7 including the Pechmann,8 Perkin,9 Knoevenagel,10,11 Reformatsky12 and Wittig5,13 reactions.However, the Pechmann reaction has been the most widely applied method for preparing coumarins since it proceeds from very simple starting materials and gives good yields of coumarins substituted in either the pyrone or benzene ring or in both.The course of the reaction depends on the substituents on the phenol, on the catalyst used and on the nature of the b-oxo ester. The Pechmann reaction has been studied with homogeneous acid catalysts such as sulfuric, hydrochloric, phosphoric8 and tri- fluoroacetic acid,14 and with Lewis acids such as zinc chloride, iron(III) chloride, tin(IV) chloride, titanium chloride and aluminium chloride.8 However, these conventional catalysts have to be used in excess, and they are subject to increasing environmental pollution and are non-recoverable.Consequently, there is a need for efficient and heterogeneous catalytic methods for this reaction by using inexpensive, easily handled and non-polluting catalysts. Cation-exchange resins,15 Nafion-H,16 zeolite-HBEA and other solid acids17 have been employed for this purpose. More recently, microwave irradiation was applied to accelerate this reaction.18 Montmorillonite clays have been used as efficient catalysts for a variety of organic reactions.19 They are inexpensive nontoxic powders which can be filtered easily from reaction mixtures and may be reused.However, syntheses of coumarins directly catalysed by montmorillonite clays have not been reported. In connection with our work on montmorillonite clays catalysis,20 herein we describe an environmentally friendly procedure for the synthesis of coumarins via Pechmann reaction catalysed by montmorillonite K-10 and KSF.As shown in Table 1, in the presence of montmorillonite clays, several phenols (1a, 1b 1f) and ethyl acetoacetate were *To receive any correspondence (e-mail: orgsyn@hbu.edu.cn). †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Scheme 1 Table 1 Synthesis of coumarin from phenols with ethyl acetoacetate catalysed by montmorillonite clays Yield(%)a Mp (T/°C) Coumarin Catalyst/solvent/ Phenol substituents temp.(T/°) t/h Found Lit. Found Reported Resorcinol (1a) 4-Me-7-OH K-10/none/150 4 96 9016 188–188.5 18416 K-10/toluene/reflux 8 94 KSF/none/150 5 88 KSF/toluene/reflux 10 90 Phloroglucinol (1b) 4-Me-5,7-(OH)2 K-10/toluene/reflux 8 85 49.115 284–285 284.5–28515 KSF/toluene/reflux 8 88 Pyrogallol (1c) 4-Methyl-7,8-(OH)2 K-10/toluene/reflux 10 66 5616 234–235 23316 m-Cresol (1d) 4,7-Me2 K-10/none/150 8 69b 2516 131.5–132 13416 KSF/none/150 12 61b p-Cresol (1e) 4,6-Me2 K-10/none/150 12 61b 014 149–150 150–15124 a-Naphthol (1f) 4-Me-7,8-benzo K-10/none/150 8 80 8521 170.5–171 17021 Phenol (1g) 4-Me K-10/none/150 10 65b 322 83–84 83–8423 2-Naphthol (1h) 4-Me-6,7-benzo K-10/none/150 12 68b 2025 182–183 18325 2-Nitrophenol (1i) no reaction K-10/none-150 12 —c 3-Nitrophenol (1j) no reaction K-10/none/150 12 —c 4-Nitrophenol (1k) no reaction K-10/none/150 12 —c 2-Chlorophenol (1l) no reaction K-10/none/150 12 —c 2,4-Dichlorophenol (1m) no reaction K-10/none/150 12 —c Hydroquinone (1n) no reaction K-10/none/150 12 —c Salicylaldehyde (1o) no reaction K-10/none/150 12 —c 4-Hydroxybenzaldehyde (1p) no reaction K-10/toluene/reflux 12 —c 2-Aminophenol (1q) no reaction K-10/toluene/reflux 12 —c 4-Aminophenol (1r) no reaction K-10/toluene/reflux 12 —c 4-(4-Nitrophenylazo)orcinol (1s) no reaction K-10/toluene/reflux 12 —c aIsolated yield.bNet yield, conversion rate of 1d=15%, conversion rate of 1e=4%, conversion rate of 1g=7%, conversion rate of 1h=5%. c100% of starting materials were recovered.J. CHEM. RESEARCH (S), 1998 39 heated in the absence of solvent or in refluxing toluene to give the corresponding coumarins in high yields. Pyrogallol (1c) afforded a good yield, m-cresol (1d), p-cresol (1e), phenol (1g) and b-naphthol (1h) provided poor conversion rates whereas nitrophenol (1i, 1j and 1k), 2-chlorophenol (1l), 2,4-dichlorophenol (1m), hydroquinone (1n), salicylaldehyde (1o), p-hydroxybenzaldehyde (1p), o-aminophenol (1q), p-aminophenol (1r) and 4-(p-nitrophenylazo)orcinol (1s) all failed to afford the corresponding coumarins.From the experimental results, it can be proved that phenols having electron-donating substituents in the position meta to the phenol hydroxy group promote the condensation. The +E effects of these substituents support formation of the reactive polarised carbonation in the ortho position. An alkyl group is not strong enough to furnish the activation needed and thus gives a low yield (1d).In contrast, electron-withdrawing groups inhibit the reaction. Generally speaking, K-10 worked better than KSF in term of reaction time and yield. The optimum amount of the catalyst used was between 25 and 30% by weight of the total reactants. Catalysts were easily regenerated by washing with ethanol, followed by drying at 110 °C for 12 h.The catalyst K-10 and KSF could be reused four times in the reaction with 1a without significant loss of activity. In conclusion, the use of montmorillonite clays as heterogeneous catalysts is a viable alternative to existing procedures. Furthermore, this method is advantageous because of easy separation, consistent yield, minimal environmental effects and recyclability of the catalyst. Experimental Melting points are uncorrected. Montmorillonite K-10 and KSF were purchased from Fluka and dried at 100 °C prior to use.Ethyl acetoaceate and all liquid phenols were distilled before use. The products were characterized by their melting points and/or IR and 1H NMR spectra and by comparison with their literature data. General Procedure for the Synthesis of Coumarins.—A mixture of the phenolic compound 1 (5 mmol), ethyl acetoaceate (5 mmol) and montmorillonite K-10 (or KSF) (30 wt% to 1 and ethyl acetoacetate) was refluxed in toluene (10 ml) using a Dean– Stark apparatus to remove water (or heated at 150 °C for those reactions in the absence of solvent) with constant stirring for 4–12 h as indicated in Table 1.The reaction was monitored by TLC. The montmorillonite was filtered off and washed with hot ethanol (2Å5 ml). The solvent was removed under reduced pressure to afford the crude product. The crude product was purified by column chromatography on silica gel [light peroleum (bp 60–90 °C)–ethyl acetate as eluent] to give the pure coumarin 2, yield 0–96% (Table 1).We are grateful to NSFC (29572039), the Science and Technology Commission of Hebei Province and the Education Commission of Hebei Province for financial support. Received, 28th May 1997; Accepted, 29th September 1997 Paper E/7/03694I References 1 Part 6, Z.-H. Zhang, F. Yang, T.-S. Li and C.-G. Fu, Synth. Commun., 1997, 27, 3823. 2 A. Schonberg and N. Latif, J. Am. Chem. Soc., 1954, 76, 6208. 3 A. Mitra, S. K. Misra and A. Patra, Synth. Commun., 1980, 10, 915. 4 L. A. Singer and N. P. Kong, J. Am. Chem. Soc., 1966, 88, 5213. 5 N. S. Narasimhan, R. S. Mali and M. V. Barve, Synthesis, 1979, 906. 6 S. M. Sethna and N. M. Shah, Chem. Rev., 1945, 36, 1. 7 S. Wawzoek, in Heterocyclic Compounds, ed. R. C. Elderfield, Wiley, New York, 1951, vol. 2, p. 173. 8 S. Sethna and R. Phadka, Org. React., 1953, 7, 1. 9 J. R. Johnson, Org. React., 1942, 1, 210. 10 G. Jones, Org. React., 1967, 15, 204. 11 G. Brufola, F. Fringuelli, O. Piermatti and F. Pizzo, Heterocycles, 1996, 43, 1257. 12 R. L. Shirner, Org. React., 1942, 1, 1. 13 R. S. Mali, S. N. Yeola and B. K. Kulkarni, Indian J. Chem., 1983, 22B, 352. 14 L. L. Woods and J. Sapp, J. Org. 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ISSN:0308-2342    

DOI:10.1039/a703694i

出版商:RSC    

年代:1998

数据来源: RSC