摘要:

Reductive Coupling of Aromatic Carbonyl Compoundsto Pinacols Using Zinc Powder in Aqueous Media$Lei Wang, Xinghua Sun and Yongmin Zhang*Department of Chemistry, Hangzhou University, Hangzhou, 310028, P.R. ChinaZinc-mediated reductive coupling of aromatic carbonyl compounds occurs to give corresponding 1,2-diols in moderateto good yields in saturated NH4Cl(aq)¡ÓTHF solution at room temperature.1,2-Diols are very useful synthons for a variety of organicsyntheses.1 The reductive coupling of carbonyl compoundsis an important method for the formation of 1,2-diols,2 andis usually carried out under anhydrous conditions.On theother hand, many reagents such as TiCl3,3 Zn¡ÓZnCl2,4Al(Hg),5 Cp2TiCl6 and Mn7 have been developed forpinacolic coupling reactions in aqueous media becauseorganic reactions in aqueous media oer a number ofadvantages over conventional organometallic reactions inorganic solvents.8 As a cheap and ecient reagent, metalliczinc powder has been used for the preparation of homo-allylic alcohols by the coupling of allylic halides with car-bonyl compounds in aqueous media.9 To the best of ourknowledge there are no literature examples of pinacoliccoupling using zinc powder in saturated NH4Cl(aq)¡ÓTHFsolution.We therefore report herein that zinc-mediatedreductive coupling of aromatic carbonyl compounds topinacols can be carried out in aqueous media at room tem-perature. The results are summarized in Table 1.Table 1 shows that aromatic aldehydes undergo couplingin the presence of zinc powder in THF¡ÓNH4Cl(aq) solutionto give pinacolic coupling products (1,2-diols) in moderateto good yields at ambient temperature. Except for that of2 g, the DL : meso ratio of diols (entries a¡Óf, h) is nearly 1:1(1H NMR).The reason for the eect of the triuoromethylgroup in the 4-position of the aromatic ring (entry g) on theDL:meso ratio is not clear. Unfortunately, the aromaticketone (entry h) gives the pinacolic coupling product inpoor yield.We have tried to use anhydrous THF, THF¡Ówater (4 :1)or water in place of THF¡ÓNH4Cl(aq) (4 :1) respectively.However, no product was formed under these conditions.Also, other metal powders such as tin and indium in placeof zinc gives no reaction.In summary, zinc is a useful metal to mediate the reduc-tive coupling of aromatic carbonyl compounds in aqueousmedia at room temperature. The advantages of this reactionare mild and neutral reaction conditions, simple operationand good yields.Experimental1H NMR spectra were recorded on a JEOL PMX 60 SIinstrument.All NMR samples were measured in CDCl3 using TMSas internal standard. IR spectra were obtained on a Perkin-Elmer683 spectrophotometer as KBr plates.General Procedure for the Preparation of Pinacols.The aromaticcarbonyl compound (1.0 mmol) and metallic zinc powder(1.2 mmol) were added to saturated aqueous NH4Cl¡ÓTHF (1:4,5 ml) solution. The resulting mixture was stirred at room tempera-ture for 8 h, then dilute hydrochloric acid (0.5 mol l£¾1, 2ml) wasadded to quench the reaction and the mixture was extracted withdiethyl ether (20 ml2).The extracts were washed with brine,J. Chem. Research (S),1998, 336¡Ó337$Table 1 Zinc-mediated reductive coupling of aromatic carbonyl compoundsEntry Ar R Yield(%)aDL : mesob 1H NMR(d) IR(~/cm£¾1)a C6H5 H 65 55 : 45 3.78 (2 H, s, OH),c 4.40 (s, DL) and 4.60 (s, meso)(2 H, 2 PhCH), 6.50¡Ó7.30 (10 H, m, Ph)3100¡Ó3600(s)b p-ClC6H4 H 77 58 : 42 2.85 (2 H, s, OH),c 4.40 (s, DL) and 4.63 (s, meso)(2 H, 2 PhCH), 6.60¡Ó7.30 (8 H, m, Ar)3200¡Ó3600(s)c p-BrC6H4 H 76 50 : 50 2.46 (2 H, s, OH),c 4.50 (s, DL) and 4.60 (s, meso)(2 H, 2 PhCH), 6.60¡Ó7.60 (8 H, m, Ar)3100¡Ó3600(s)d p-FC6H4 H 73 55 : 45 3.15 (2 H, s, OH),c 4.55 (s, DL) and 4.70 (s, meso)(2 H, 2 PhCH), 6.60¡Ó7.50 (8 H, m, Ar)3150¡Ó3620(s)e m-BrC6H4 H 70 52 : 48 3.33 (2 H, s, OH),c 4.33 (s, DL) and 4.50 (s, meso)(2 H, 2 PhCH), 6.70¡Ó7.40 (8 H, m, Ar)3100¡Ó3500(s)f o-BrC6H4 H 68 50 : 50 2.90 (2 H, s, OH),c 4.55 (s, DL) and 4.65 (s, meso)(2 H, 2 PhCH), 6.70¡Ó7.50 (8 H, m, Ar)3100¡Ó3600(s)g p-CF3C6H4 H 82 74 : 26 3.04 (2 H, s, OH),c 4.45 (s, DL) and 4.66 (s, meso)(2 H, 2 PhCH), 6.65¡Ó7.50(8 H, m, Ar)3100¡Ó3600(s)h C6H5 CH3 32 51 : 49 1.42 (s, DL) and 1.55 (s, meso) (6 H, 2 CH3), 2.40(2 H, s, OH),c 6.80¡Ó7.30 (10 H, m, Ph)3100¡Ó3600(s)aIsolated yields.bRatios determined from the intensities of benzylic protons in 1H NMR spectra(entries a¡Óg), in which the protons ofthe DL isomer appeared at a higher magnetic field compared to that of the meso isomer, or from the intensities of methyl protons in1H NMR spectra(entry h), in which the methyl protons of the DL isomer appeared at higher magnetic field compared to that of the mesoisomer.10 cIn all examples this signal disappeared on adding D2O.dried over anhydrous Na2SO4 and the solvent was removed underreduced pressure.The residue was then puried by preparative TLCon silica gel with light petroleum¡Óether as the eluent to give theproduct.$This is a Short Paper as dened 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.336 J. CHEM. RESEARCH (S), 1998Received, 20th January 1998; Accepted, 25th February 1998 Paper E/8/00478A References 1 A. Ghribi, A. Alexakis and J. F.Normant, Tetrahedron Lett., 1984, 3083. 2 B. E. Kahn and E. D. Rieke, Chem. Rev., 1988, 88, 733; J. M. Pons and M. Santelli, Tetrahedron, 1988, 44, 4295. 3 A. Clerici and O. Porta, Tetrahedron Lett., 1982, 23, 3517. 4 K. Tanaka, S. Kishigami and F. Toda, J. Org. Chem., 1990, 55, 2981. 5 M. Hulce and T. LaVaute, Tetrahedron Lett., 1988, 29, 525. 6 M. C. Barden and J. Schwartz, J. Am. Chem. Soc., 1996, 118, 5484. 7 C. J. Li, Y. Meng, X. H. Yi, J. Ma and T. H. Chan, J. Org. Chem., 1997, 62, 8632. 8 C. J. Li, Chem. Rev., 1993, 93, 2023; A. Lubineau, J. Auge and Y. Queneau, Synthesis, 1994, 741; C. J. Li, Tetrahedron, 1996, 52, 5643. 9 C. Petrier and J. L. Luche, J. Org. Chem., 1985, 50, 910; J. Einhorn and J. L. Luche, J. Organomet. Chem., 1987, 322, 177; S. R. Wilson and M. E. Guazzaroni, J. Org. Chem., 1989, 54, 3087. 10 Y. Handa and J. Inanaga, Tetrahedron Lett., 1987, 28, 5717; R. E. Balsells and A. R. Frasca, Tetrahedron, 1982, 38, 2525. J. CHEM. RESEARCH (S), 1998 337

ISSN:0308-2342    

DOI:10.1039/a800478a

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Amination of Optically Active Azaallylic Anions$% Stefania Fioravanti, Lauso Olivieri, Lucio Pellacani* and Paolo A. Tardella* Dipartimento di Chimica, Universita¢® `La Sapienza', P.le Aldo Moro 2, I-00185 Roma, Italy The reaction of azaallylic anions with ethyl N-[4-nitrobenzenesulfonyl)oxy]carbamate in the presence of a base gives a mixture of an -amino ketone derivative with a slight preference for the (S) enantiomer and of an -hydrazino ketone derivative as by-product; the same azaenolates react with bis(tert-butoxycarbonyl)diazene giving the analogous -hydrazino ketone derivative, with a slight preference for the (R) enantiomer.Chiral enamines, imines and hydrazones allow good enantio- and diastereo-selectivity in carbon¡¾carbon bond- forming reactions.1 We have recently been exploring the for- mation of carbon¡¾nitrogen bonds starting from enamines.2 Our attention was then directed towards the amination reaction of azaallylic anions derived from imines.In this paper we describe results concerning the reactions of two aminating agents, namely ethyl N-[(4-nitrobenzene- sulfonyl)oxy]carbamate (NsONHCO2Et) and bis(tert- butoxycarbonyl)diazene [N2(CO2But)2, TBD] with azaallylic anions. The reaction of NsONHCO2Et in the presence of LiOH was ¢çrst carried out with the N-cyclohexylidene- benzylamine lithium salt 1 in order to optimise the yields of 2-[(ethoxycarbonyl)amino]cyclohexanone 2 (Scheme 1). The best results were obtained using a mixture of THF or DME and CH2Cl2.As a base we ¢çrst chose LiOH in order to have a common cation in the reaction mixture. The best conditions are those of entry 5 (Table 1). We note that this is the ¢çrst successful amination by NsONHCO2Et at low temperatures, although electrophilic amination by TBD of ester enolates3 and chiral amide cuprates4 has been reported. The reaction was then extended to chiral substrates 3 and 4 (Scheme 2). The chiral metallated hydrazone 5, usually employed in alkylation reactions,5 was unreactive.In Table 2 the results of reactions run using NsONHCO2Et are collected. Entries 1, 7 and 9 refer to the best conditions of Table 1. The major enantiomer of 2 showed an S con¢çguration6 as expected on the basis of an attack from the less hindered side and as previously noted in the amination of (S)-(¢§)-1- (1-cyclohexenyl)-2-(methoxymethyl)pyrrolidine in the presence of calcium oxide.2b When the anion was generated by the use of KH (entries 4, 6 and 8) the e.e.rose slightly, according to data reported for the alkylation of N,N-disubstituted amides.7 The large excess of LiOH required for the NsONHCO2Et deprotonation, might be responsible for the low e.e. observed in the aminations of 4, probably interfering with the formation of a rigid ¢çve membered chelate.8 J. Chem. Research (S), 1998, 338¡¾339$ Scheme 1 Scheme 2 Table 1 Amination of compound 1 with NsONHCO2Et and LiOH Molar ratio Reaction Yield of Entry Solvent T (8C) 1: NsONHCO2Et: LiOH time (h) 2 (%) 1 THF 0 1:3:10 20 2 2 THF ¢§50 1:3:10 24 5 3 DME ¢§70 1:3:10 3 16 4 THF/CH2Cl2 ¢§70 1:3:10 2 10 5 DME/CH2Cl2 ¢§70 1:3:10 3 32 6 DME/CH2Cl2 ¢§70 1:5:10 3 31 TBD gives a slow amination reaction only in the presence of HMPA, showing a lower reactivity towards this kind of azaenolates than that observed towards enolates.9 The reaction conditions and the yield of 2-[N,N'-bis(tert- butoxycarbonyl)hydrazino]cyclohexanone 7 (Scheme 3) are reported in Table 3.The R con¢çguration of the major enan- $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). %Presented in part at the XXIII Convegno Nazionale della Divisione di Chimica Organica della SocietaA Chimica Italiana, Monopoli, Italy, September 22¡¾27, 1996, P99. *To receive any correspondence (e-mail: pellacani@uniroma1.it). 338 J. CHEM. RESEARCH (S), 1998tiomer and the e.e. values were established on the basis ofthe [a]D values (see Experimental section). In this case theobserved reversal of facial selectivity might be rationalised ifone assumes a role of HMPA, as suggested in alkylation ofhydrazone lithio anions.10Free bases of the salts 1, 3 and 5, were treated directlywith TBD in toluene at reux, under conditions reported forMichael additions to the same substrates.11 After 2¡Ó5 h ofheating and subsequent hydrolytic work-up, the rst twobases gave the same product 7 in 45 and 30% yield, respect-ively.In the last case only 5% e.e. was found.ExperimentalGeneral Procedure for the Reactions of 1 with NsONHCO2Et.Asolution of BunLi in hexane (Fluka, 25 mmol, 1.6 M) was addeddropwise to a solution of diisopropylamine (25 mmol) in 20 ml ofTHF or DME, under nitrogen at 0 8C, and stirred for 30 minto obtain LDA. Then N-cyclohexylidenebenzylamine (20 mmol) in150 ml of anhydrous THF or DME or CH2Cl2 (Table 1, entries4¡Ó6) was added slowly and the mixture stirred for 1.5 h.AnhydrousLiOH (Carlo Erba) was added batchwise and NsONHCO2Et addedportionwise in 30 min. The mixture was allowed to warm to roomtemperature, poured into water¡ÓTHF, acidied to pH13 with 1 Moxalic acid and extracted with diethyl ether. Compound 212 wascollected by ash chromatography on silica gel (hexane¡Ódiethylether, 1:1) in the yields reported in Table 1.Reaction of 3, 4 and 5 with NsONHCO2Et.The general pro-cedure was followed, changing the cation (entries 4¡Ó6, 8 and 10 ofTable 2), the bases (entries 2, 3, 5 and 6) and the molar ratios(entries 2 and 3).After work-up, the products 2 and/or 613 wereseparated by ash chromatography on silica gel. The e.e. wasevaluated upon conversion into diastereomeric ketals with (2R,3R)-2,3-butanediol.6 6: C 14.20, 24.14 (CH3) 26.56, 29.52, 30.58, 41.18(CH2), 61.84 (NCH), 62.19, 62.75 (OCH2), 156.65 (CO2) and 207.67(CO).Reaction of 3, 4 and 5 with TBD.A solution of BunLi inhexane (50 mmol, 1.6 M) was added dropwise to a solution ofdiisopropylamine (50 mmol) in 200 ml of THF, under nitrogen at0 8C, and stirred to obtain LDA.After 30 min HMPA (50 ml) and3, 4 or 5 (20 mmol) in 100 ml of anhydrous THF were added slowlyand the mixture was stirred for 1.5 h. TBD (Fluka) in 100 ml ofTHF was added in the molar ratios reported in Table 3. After 1 h,the mixure was allowed to warm to room temperature and stirred(3¡Ó8 d) in the dark.After work-up with water¡ÓTHF and 1 M oxalicacid, the mixture was extracted with diethyl ether and the organiclayer washed with a saturated solution of NaCl. Compound 72b wascollected by ash chromatography on silica gel (hexane¡Óethylacetate, 8 : 2) in the yields and e.e. reported in Table 3. The e.e. wasobtained by comparison between the []D values (25 8C, c 0.12 inCH2Cl2) for 7 and that previously measured for a dierent enantio-meric mixture of the same -hydrazino ketone derivative (£¾12,CH2Cl2).2bReaction of free bases of 1, 3 and 5 with TBD.A solution ofsubstrate (10 mmol) and TBD (12 mmol) and 50 ml of toluenewas reuxed for 2¡Ó9 h.The mixture was poured into water¡ÓEtOH,acidied with 1 M oxalic acid and extracted with diethyl ether. Afterwork-up, starting from the rst two bases the product 7 wasobtained by ash chromatography on silica gel (hexane¡Óethylacetate, 8 : 2).Starting from the free base of 5, only the substratewas recovered by ash chomatography.This work was supported by the Ministero dell'Universitae della Ricerca Scientica e Tecnologica (MURST) and theConsiglio Nazionale delle Ricerche (CNR, Roma).Received, 24th December 1997; Accepted, 23rd February 1998Paper E/7/09277FReferences1 P. W. Hickmott, Tetrahedron, 1982, 38, 3363.2 (a) S. Fioravanti, L. Pellacani, D. Ricci and P. A. Tardella,Tetrahedron: Asymmetry, 1997, 8, 2261; (b) S.Fioravanti,L. Pellacani and P. A. Tardella, Gazz. Chim. Ital., 1997, 127, 41.3 J. P. Genet, S. Mallart, C. Greck and E. Piveteau, TetrahedronLett., 1991, 32, 2359.4 N. Zheng, J. D. Armstrong III, J. C. McWilliams and R. P.Volante, Tetrahedron Lett., 1997, 38, 2817.5 (a) D. Enders, H. Eichenauer, U. Baus, H. Schubert andK. A. M. Kremer, Tetrahedron, 1984, 40, 1345; (b) D. Enders,W. Gatzweiler and E. Dederichs, Tetrahedron, 1990, 46, 4757.6 S. Fioravanti, M. A. Loreto, L. Pellacani and P.A. Tardella,J. Chem. Res. (S), 1987, 310.7 M. Larcheveque, E. Ignatova and T. Cuvigny, TetrahedronLett., 1978, 3961.8 A. I. Meyers, D. R. Williams, G. W. Erickson, S. White andM. Druelinger, J. Am. Chem. Soc., 1981, 103, 3081.9 G. Guanti, L. Ban and E. Narisano, Tetrahedron, 1988, 44,5553; D. E. Evans, T. C. Britton, R. L. Dorow and J. F.Dellaria, Jr., Tetrahedron, 1988, 44, 5525.10 K. G. Davenport, H. Eichenauer, D. Enders, M. Newcomb andD. E. Bergbreiter, J. Am. Chem. Soc., 1979, 101, 5654.11 J. D'Angelo, D. Desmae le, F. Dumas and A. Guingant,Tetrahedron: Asymmetry, 1992, 3, 459.12 T. Hiyama, H. Taguchi, S. Fujita and H. Nozaki, Bull. Chem.Soc. Jpn., 1972, 45, 1863.13 R. M. Moriarty and I. Prakash, Synth. Commun., 1985, 15, 649.Table 2 Amination of compounds 3, 4 and 5 with NsONHCO2EtAdded Molar ratio Yield of 2 Yield of 6Entry Substrate M base substrate:NsONHCO2Et base (e.e., %) (e.e., %)1 3 Li LiOH 1:3:10 23% (28) ¡Ó2 3 Li Et3N 1:3:3.5 ¡Ó 22% (¡Ó)3 3 Li ¡Ó 2:1:¡Ó ¡Ó 13% (¡Ó)4 3 K LiOH 1:3:10 25% (34) 10% (8)5 3 K K2CO3 1:3:10 ¡Ó ¡Ó6 3 K CaO 1:3:10 13% (30) 10% (8)7 4 Li LiOH 1:3:10 12% (24) ¡Ó8 4 K LiOH 1:3:10 10% (36) 5% (9)9 5 Li LiOH 1:3:10 ¡Ó ¡Ó10 5 K LiOH 1:3:10 ¡Ó ¡ÓTable 3 Amination of compounds 3, 4 and 5 with TBDSubstrateMolar ratioHMPA: substrate:TBDTime(d)Yield of 7(e.e., %)[a]Dof 73 7:1:2.5 3 23% (¡Ó) ¡Ó4 6:1:1.25 4 19% (29) 9.05 6:1:1.25 8 28% (33) 11.2Scheme 3J. CHEM. RESEARCH (S), 1998 339

ISSN:0308-2342    

DOI:10.1039/a709277f

出版商:RSC    

年代:1998

数据来源: RSC

ISSN:0308-2342    

DOI:10.1039/a800135i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Organic Synthesis with Anion-exchange Resins:Reaction of Imines with Active MethyleneCompounds$Dilip Konwar,* Dilip Kumar Dutta and Birendra Nath GoswamiRegional Research Laboratory, Jorhat-785 006, Assam, IndiaImines undergo addition¡Óelimination reaction with active methylene compounds in the presence of Amberlite IRA-400(OH£¾) as catalyst to yield arylidenemalononitrile derivatives.Polymer-supported methods rst developed by Merrield1in polypeptide synthesis have been utilised in many trans-formations in organic chemistry.2 In recent years thecombinatorial chemistry has received much attention inorganic synthesis.3Anion-exchange resins, particularly Amberlite IRA-400,have been shown to be excellent catalysts in various organicreactions, for example aldol condensation,4 Knovenageland Michael condensation,5 cyanohydrin formation,6 etc.Recently, they have been in phenyl sulde formation7 andselective reduction of alkyl halides to alkanes.8 We reporthere an addition¡Óelimination reaction between imines andactive methylene compounds in the presence of AmberliteIRA-400 (OH£¾) as catalyst to give synthetically usefularylidenemalononitrile derivatives9 (Scheme 1).The reaction was carried out by stirring the imines 1a¡Ójand the active methylene compounds 2a¡Óc in the presence ofa molar equivalent of Amberlite IRA-400 (OH£¾) in ethanolunder reux.The product was obtained by simple ltrationevaporation of the solvent under reduced pressure andcrystallisation from appropriate solvents.The results aresummarized in Table 1.In conclusion, we have observed that the anion-exchange resin Amberlite IRA-400 (OH£¾) can rapidlyexchange its labile hydroxide ion with the enolate of theactive methylene compounds in ethanol solution producingAmberlite IRA 400 (HCR0CN£¾) which reacts with theazomethine carbon of the imines and eliminates amines insolution. Work is in progress to understand the mechanismof the reaction.ExperimentalThe mps were measured in a Buchi apparatus and are un-corrected.IR spectra were recorded on a Perkin-Elmer 237B spec-trophotometer, 1H NMR spectra on a Varian T-60 spectrometerwith TMS as internal standard and mass spectra on an AEIMS-30spectrometer The anion-exchange resin Amberlite IRA-400 wasusually purchased from Aldrich as the chloride salt (16¡Ó60 mesh).This conversion into the hydroxide form was accomplished bywashing with 1 M sodium hydroxide until the eluent gave a negativesilver nitrate test for chloride ion.The resin was thoroughly washedwith distilled water, dried for several hours at 40 8C and kept in avacuum desiccator for 24 h. before use. The imines were preparedby the literature method10 or a slight modication thereof.Preparation of Arylidene Malononitrile 3a.In a typical exper-iment, malononitrile (1.32 g, 0.02 mol) in ethanol (25 ml) wasmixed with Amberlite IRA-400 (OH£¾) (7.3 g, 0.02 mol) having acapacity of 2.8 milliequvalent per dry g and benzylideneaniline 1a(3.62 g, 0.02 mol) was stirred for 4 h at the reux temperatureof ethanol.The reaction mixture was ltered through a pad ofCelite and the solvent evaporated under reduced pressure to give aresidue which on crystallation from light petroleum (bp 40¡Ó60 8C)yielded arylidenemalononitrile 3a as white needles, mp 87 8C(lit.,11 87 8C). Yield: 2.5 g (82%). The other nitriles were preparedsimilarly.We wish to express our sincere thanks to Dr N.Borthakur and Dr J.C. S. Kataky, scientists, and Dr J. S.Sandhu, Acting Director, Regional Research Laboratory,Jorhat for their keen interest and help in carrying out thiswork.Received, 3rd February 1998; Accepted, 2nd March 1998Paper E/8/00951AReferences1 R. B. Merried, J. Am. Chem. Soc., 1963, 85, 2194.2 Organic Synthesis, Today and Tomorrow, ed. B. M. Trost andC. R. Hutchison, Pergamon Press, Oxford, 1981, pp. 19¡Ó28 andreferences therein.3 J. S. Fruch and G. Jung, Angew.Chem, Int. Ed. Engl., 1936, 35,2194.4 G. V. Austerwell and R. Palloud, Bull. Soc. Chim. Fr., 1963, 678;P. Mastagi, Z. Zariadis, G. Durr, A. Floch and G. Lagrange,Bull Soc. Chim. Fr. 1953, 693; M. H. Astle and J. A. Zaslowsky,Bull Soc. Chim. Fr. 1952, 2867.5 B. W. Howk and C. M. Langkaminerer, U.S. Pat., 2 579 580,25th December, 1951; E. D. Bergmann and R. Corret, J. Org.Chem., 1956, 21, 107; 1958, 23, 1507.Scheme 1Table 1 Synthesis of arylidenemalononitriles 3a¡ÓjaEntry R R0 t/h Yield (%)1 Ph CN 5 822 p-ClC6H4 CN 4.5 803 p-O2NC6H4 CN 4 754 CN 4.5 705 CN 5 656 Ph CONH2 4 797 Ph CN 5 828 CONH2 5 659 Ph-CH1CH CO2Et 6 6510 Ph CO2Et 6 70aAll the compounds gave satisfactory spectroscopic analyses andwere comparable with authentic samples.J. Chem.Research (S),1998, 342¡Ó343$$This is a Short Paper as dened 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.342 J. CHEM. RESEARCH (S), 19986 C. J. Schmidle and R. C. Mans®eld, Ind. Eng. Chem., 1952, 44, 1388. 7 N. M. Yoon, J. Choi and H. J. Ahn, J. Org. Chem., 1994, 59, 3490. 8 N. M. Yoon, J. H. Lee, H. J. Ahn and J. Choi, J. Org. Chem., 1994, 59, 4687. 9 F. Freeman, Chem. Rev., 1969, 69, 591; 1980, 80, 329; Synthesis, 1981, 925. 10 The Chemistry of Carbon Nitrogen Double Bond, ed. S. Patai, Wiley, New York, 1970. 11 P. J. Bhuyan, R. C. Boruah and J. S. Sandhu, J. Org. Chem., 1990, 55, 568. J. CHEM. RESEARCH (S), 1998 343

ISSN:0308-2342    

DOI:10.1039/a800951a

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Synthesis and Characterization of m-AlkyneMolybdenum¡Ó and Tungsten¡ÓCobalt Clusterscontaining Functionally SubstitutedCyclopentadienyl Ligands$Li-Cheng Song,* Qing-Mei Hu, Jin-Song Yang and Jin-Yu ShenDepartment of Chemistry, Nankai University, Tianjin 300071, ChinaEight new -alkyne molybdenum¡Ó and tungsten¡Ócobalt clusters containing functionally substituted cyclopentadienylligands have been synthesized via organic carbonyl transformation reactions of clusters [(5-MeCOC5H4)(OC)2M-(-C2Ph2)Co(CO)3] (M Mo or W).Transition-metal clusters, particularly those containingfunctionally substituted cyclopentadienyl ligands are ofgreat interest due to their potential applications in catalyticprocesses1¡Ó4 and for synthesizing a variety of novel clusterderivatives which would be dicult or even not possible byother methods.5,6 Herein we report some transformationreactions of the carbonyl group on the cyclopentadienylring of clusters [(Z5-MeCOC5H4)(OC)2(m-C2Ph2)Co(CO)3](M Mo or W), from which eight new m-alkyne molyb-denum¡Ó and tungsten¡Ócobalt cluster derivatives wereobtained.We found that clusters [(Z5-MeCOC5H4)(OC)2M-(m-C2Ph2)Co(CO)3] (A, M Mo; B, M W) could bereduced by NaBH4 in methanol to give secondary alcoholclusters 1 and 2, whereas they reacted with MeMgI followedby acidic hydrolysis to give tertiary alcohol clusters 3 and 4,respectively.More interestingly, reactions of A and B with2,4-dinitrophenylhydrazine aorded their phenylhydrazonederivatives 5 and 6, whereas when treated with Wittigreagent Ph3P1CH2 they gave corresponding olenic clusterderivatives 7 and 8, respectively.All the reactions mentionedare summarized in Scheme 1.Compounds 1¡Ó8 are all new functional cyclopentadienylMCoC2 clusters (M Mo or W), which have been wellcharacterized by elemental analysis, IR, 1H NMR and MSdata. For example, the IR spectra of 1¡Ó4 show the hydroxylgroup absorption bands at 3400¡Ó3436 cm£¾1; 5¡Ó8 exhibit theabsorption bands characteristic of the functional groupsof C1N at 1614 cm£¾1 and C1C at 1625¡Ó1630 cm£¾1,respectively.The 1H NMR spectra of 1¡Ó8 reveal all thecorresponding protons, such as those of the hydroxylgroups of 1¡Ó4 between d 1.46 and 1.60, the protons of the2,4-dinitrophenyl groups of 5, 6 at d 7.83¡Ó9.20, and thoseattached to the double bond of 7, 8 at d 4.84¡Ó5.13.ExperimentalIR and 1H NMR spectra were recorded on a Nicolet FT-IR 5DXspectrophotometer and a JEOL FX 90Q spectrometer.Analyses(C, H), MS and melting point were determined using a Perkin-Elmer 240C model analyzer, a HP 5988A spectrometer and aYanako MP-500 instrument, respectively. All reactions werecarried out under nitrogen. Commercial NaBH4, Ph3PCH3Br and2,4-dinitrophenylhydrazine were used as received; MeMgI7 and[(Z5-MeCOC5H4)(OC)2M(m-C2Ph2)Co(CO)3] (M Mo or W)8 wereprepared according to literature methods.Preparations.Compounds of 1 and 2. A 50 ml two-necked askwas charged with [(5-MeCOC5H4)(OC)2M(-C2Ph2)Co(CO)3] A(58 mg, 0.1 mmol) or [(5-MeCOC5H4)(OC)2W(-C2Ph2)Co(CO)3] B(69 mg, 0.1 mmol), NaBH4 (7.6 mg, 0.2 mmol) and MeOH (3 ml).The mixture was stirred for 1.5 h at r.t.and then subjected toTLC using CH2Cl2 as eluent to give 1 or 2. 1: red oil, yield 76%;~max/cm£¾1 2057, 2000, 1975, 1926 (C2O), 3400 (OH); H (CDCl3)1.40 (d, 3 H, J 7.2, CH3), 1.46¡Ó1.60 (br, 1 H, OH), 4.48 (q, 1 H,J 7.2 Hz, CH), 5.18¡Ó5.54 (m, 4 H, C5H4), 7.10¡Ó7.58 (m, 10 H,2C6H5); m/z 402 (M £¾ 2Ph £¾ CO, 1), 181 (C2CoMo, 3%)(Found: C, 53.74; H, 3.26.C26H19CoMoO6 requires C, 53.63; H,3.29%). 2: red oil, yield 51%; ~max/cm£¾1 2049, 2000, 1975, 1926(C2O), 3435 (OH). H (CDCl3) 1.40 (d, 3 H, J 7.2, CH3), 1.48¡Ó1.60 (br, 1 H, OH), 4.50 (q, 1 H, J 7.2 Hz, CH), 5.20¡Ó5.58 (m, 4 H,C5H4), 7.00¡Ó7.40 (m, 10 H, 2C6H5); m/z 614 (M £¾ 2CO, 8), 267(C2CoW, 5%) (Found: C, 47.08; H, 2.63. C26H19CoO6W requiresC, 46.59; H, 2.86%).Compounds 3 and 4. A 50 ml two-necked ask was chargedsequentially with diethyl ether (10 ml), A (197 mg, 0.34 mmol) or B(227 mg, 0.34 mmol) and MeMgI¡Ódiethyl ether solution (0.59 M,2.0 ml) with stirring at r.t.After stirring for 3 h, distilled water(50 ml) and dilute HCl (0.167 M, 10 ml) were added. The etherphase was separated and the aqueous phase extracted with diethylether (210 ml). All the ether layers were combined. After removalof the ether, the residue was subjected to TLC separation usingCH2Cl2¡Ólight petroleum (bp 60¡Ó90 8C) (2 :1) as eluent to give 3 or4. 3: red oil, yield 12%; ~max/cm£¾1 2049, 2000, 1975, 1934 (C2O),3436 (OH); dH (CDCl3) 1.52 (s, 6 H, 2CH3), 1.40¡Ó1.50 (br, 1 H,OH), 5.14 (t, 2 H, J 2.4, H3, H4), 5.48 (t, 2 H, J 2.4 Hz, H2, H5),7.12¡Ó7.48 (m, 10 H, 2C6H5); m/z 542 (M £¾ 2CO, 0.3), 181(C2CoMo, 0.4%) (Found: C, 54.80; H, 3.62. C27H21CoMoO6requires C, 54.38; H, 3.55%). 4: red oil, yield 15%; ~max/cm£¾1 2049,2000, 1975, 1926 (C2O), 3403 (OH); dH (CDCl3) 1.54 (s, 6 H,2CH3), 1.46¡Ó1.56 (br, 1 H, OH), 5.32 (t, 2 H, J 2.4, H3, H4), 5.52(t, 2 H, J 2.4 Hz, H2, H5), 7.28 (s, 10 H, 2C6H5); m/z 628J.Chem. Research (S),1998, 344¡Ó345$Scheme 1$This is a Short Paper as dened 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.344 J. CHEM. RESEARCH (S), 1998(M £¾ 2CO, 0.5), 267 (C2CoW, 3%) (Found: C, 49.09; H, 3.02.C27H21CoO6W requires C, 47.40; H, 3.09%).Compounds 5 and 6. A 50 ml two-necked ask was charged withA (150 mg, 0.26 mmol) or B (400 mg, 0.26 mmol) and anhydrousethanol (5 ml), to which was slowly added a 2,4-dinitrophenylhydra-zine solution (1.5 ml, 0.52 mmol) (prepared by dissolving 1.0 g of2,4-dinitrophenylhydrazine in 5 ml of 98% H2SO4, 10ml of H2Oand 35 ml of 95% C2H5OH) with stirring.After stirring at r.t. for1.5 h to give a precipitate, which was puried by TLC usingCH2Cl2¡Ólight petroleum¡Ódiethyl ether (1:5:1) as eluent to aord 5or 6. 5: brown-red solid, mp 95 8C (decomp.), yield 41%; ~max/cm£¾12049, 1983, 1942 (C2O), 1614 (C1N); dH (CDCl3) 1.72 (s, 3 H,CH3), 5.52 (s, 2 H, H3, H4 of C5H4 ring), 5.76 (s, 2 H, H2, H5of C5H4 ring), 7.20 (s, 10 H, 2C6H5). 7.83 (d, 1 H, J 9.8, H6 ofbenzene ring), 8.30 (d, 1 H, J 9.8 Hz, H5 of benzene ring), 9.20(s, 1 H, H3 of benzene ring), 10.88 (s, 1 H, NH) (Found: C, 51.00;H, 3.29; N, 7.58. C32H21CoMoN4O9 requires C, 50.54; H, 2.78;N, 7.37%). 6: brown-red solid, mp 128 8C (decomp.), yield 72%;~max/cm£¾1 2049, 2000, 1975, 1934 (C2O), 1614 (C1N); dH(CDCl3) 1.70 (s, 3 H, CH3), 5.62 (t, 2 H, J 2.5, H3, H4 of C5H4ring), 5.82 (t, 2 H, J 2.5, H2 H5 of C5H4 ring), 7.21 (s, 10 H,2C6H5) 7.85 (d, 1 H, J 9.7, H6 of benzene ring), 8.36 (d, 1 H, J9.7 Hz, H5 of benzene ring), 9.18 (s, 1 H, H3 of benzene ring), 10.91(s, 1 H, NH) (Found: C, 45.13; H, 2.60; N, 6.85.C32H21CoN4O9Wrequires.C, 45.31; H, 2.50; N, 6.61%).Compounds 7 and 8. A 50 ml two-necked ask was chargedwith Ph3PCH3Br (528 mg, 1.48 mmol) and THF (20 ml), to whichwas slowly added a BunLi¡Óhexane solution (1.06 M, 1.4 ml) at 0 8Cand then stirred for 4 h at r.t. to give a mixture containing Wittigreagent Ph3P1CH2. To this was added 10 ml of a THF solutionof A (429 mg, 0.74 mmol) or B (494 mg, 0.74 mmol) and then themixture was stirred for 3 h at r.t. It was subjected to TLC usingCH2Cl2¡Ólight petroleum (1: 3) as eluent to give 7 or 8. 7: red solid,mp 56¡Ó57 8C, yield 43%; ~max/cm£¾1 2041, 2007, 1975, 1934 (C2O),1625 (C1C); dH (CDCl3) 1.76 (s, 3 H, CH3), 4.84 (s, 1 H, C1CH),5.13 (s, 1 H, C1CH), 5.20 (s, 2 H, H3, H4), 5.48 (s, 2 H, H2, H5),7.23 (s, 10 H, 2C6H5); m/z 524 (M £¾ 2CO, 7%) (Found: C, 56.88;H, 3.60. C27H19CoMoO5 requires C, 56.94; H, 3.54%). 8: red solid,mp 78¡Ó80 8C, yield 23%; ~max/cm£¾1 2041, 2000, 1975, 1942 (C2O),1631 (C1C); dH (CDCl3) 1.72 (s, 3 H, CH3), 4.86 (s, 1 H, C1CH),5.10 (s, 1 H, C1CH), 5.30 (s, 2 H, H3, H4), 5.52 (s, 2 H, H2, H5),7.18 (s, 10 H, 2C6H5); m/z 610 (M £¾ 2CO, 9%) (Found: C, 48.95;H, 3.10.C27H19CoO5W requires C, 48.68; H, 2.87%).We thank the National Natural Science Foundation ofChina, the Laboratory of Organometallic Chemistry and theSpecial Foundation of State Education Committee of Chinafor nancial support.Received, 13th January 1998; Accepted, 2nd March 1998Paper E/8/00350EReferences1 E. L. Muetterties and M. J. Krause, Angew. Chem., Int. Ed.Engl., 1983, 22, 135.2 M. D. Curtis, J. E. Penner-Hahn, J. Schwank, O. Baralt, D. J.McCabe, L. Thompson and G. Waldo, Polyhedron, 1988, 7, 2411.3 M. R. DuBois, Chem. Rev., 1989, 89, 1.4 P. Braunstein and J. Rose, in Comprehensive OrganometallicChemistry II, ed. E. W. Abel, F. G. A. Stone and G. Wilkinson,Pergamon, Oxford, 1995, vol. 10, p. 351.5 L-C. Song, J-Y. Shen, Q-M. Hu and X-Y. Huang, Organo-metallics, 1995, 14, 98.6 L-C. Song, J-Y. Shen, Q-M. Hu and X-Y. Huang, Inorg. Chim.Acta, 1996, 249, 175.7 H. Gilman, E. A. Zoellner and J. B. Dickey, J. Am. Chem. Soc.,1929, 51, 1576.8 L-C. Song, J-Y. Shen, Q-M. Hu, B-S. Han, R-J. Wang and H-G.Wang, Inorg. Chim. Acta, 1994, 219, 93.J. CHEM. RESEARCH (S), 1998 345

ISSN:0308-2342    

DOI:10.1039/a800350e

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Preparation and Electrooxidative SO-Extrusion of Halogenated 7-Thiabicyclo[2.2.1]heptene 7-Oxides$ Thies Thiemann,*a,b M. Luisa Sa¡� e Melo,a Andre¡� S. Campos Neves,*a Yuanqiang Li,b Shuntaro Mataka,b Masashi Tashiro,b Uwe Gei¡Ælerc and David Waltonc aDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Coimbra, P-3000 Coimbra, Portugal bInstitute of Advanced Material Study, Kyushu University, 6-1, Kasuga-koh-en, Kasuga-shi, Fukuoka 816, Japan cSchool of Natural and Environmental Sciences, Coventry University, Coventry CV1 5FB, UK Halogenated thiophenes have been cycloadded oxidatively to maleimides to give halogenated thiabicyclo[2.2.1]heptene S-oxides which have been subjected to an electrochemical extrusion of SO to give various halogeno-substituted phthalimides.Torssell1 and Fallis and co-workers2 have shown that oxidative cycloaddition occurs on treating alkyl-substituted thiophenes with m-chloroperbenzoic acid (m-CPBA) in the presence of an electron-poor dienophile.We have studied the reaction in greater detail and found it valuable to synthesize novel alkyl-substituted 7-thiabicyclo[2.2.1]heptene 7-oxides in connection with crown ether systems.3 Recently, it was shown that the yield for the oxidative cycloaddition of alkyl-substituted thiophenes, proceeding via intermediate thiophene S-monoxides, could be greatly enhanced by add- ing BF3 Et2O to m-CPBA.4 While the uncatalysed reaction can be run at 0 8C to ambient temperature, the catalysed reaction is run typically at ¢§78 8C.The greater stability of thiophene S-oxides towards further oxidation under catalysed conditions was demonstrated.4,5 The further oxidation of thiophene S-monoxides to the S,S-dioxides is a main side reaction in the oxidative cycloaddition. Oxidation of thiophenes at sulfur proceeds readily when the thiophenes are substituted with electron donors such as alkyl groups. Electron-withdrawing or more ambidentate substituents hinder the oxidation.For this reason the oxidative cycloaddition of halogenated thiophenes does not proceed well at room temperature. Nevertheless, at more elevated temperatures, 7-thiabicyclo[2.2.1]heptene S-oxides from readily in the reaction of 2,5-chlorinated or bromi- nated thiophenes with such idenophiles as maleimides or maleic anhydride (Scheme 1). The products are not very soluble in dichloromethane and partly precipitate during the reaction. Further precipitation can be induced by addition of diethyl ether.Apart from diligent washing with diethyl ether, the products need no additional puri¢çcation for a further transformation, although for analytical purposes column chromatography and recrystallization have been performed. It has been found that the addition of BF3 Et2O has no bene¢çcial e€ect on the reaction, if the thiophene is halo- genated at position 2 and/or 5. In the case of 3,4-dibromo- 2,5-dimethylthiophene 1d, however, an acceptable yield of the cycloadduct was obtained when the reaction was run at ¢§20 8C in presence of BF3 Et2O.In the cycloaddition ¢çve stereocentres are created. Nevertheless, only one isomer is isolated. Although no crystal structural analysis has been performed, it is thought to be the endo-product with the lone-electron pair of the sulfur directed to the newly formed ole¢çnic bond. This is evidenced by comparison to compounds formed in cyclo- additions with donor-substituted compounds.3¡¾5 Thiabicyclo[2.2.1]heptene S-oxides of type 3 are quite stable thermally and extrude SO only in excess of 150 8C.6 On the other hand, 3 may be viewed as precursors for corre- sponding arenes.Photochemical6 and oxidative extrusion3 of SO in 3 has been found to proceed at much lower tem- peratures than the purely thermal extrusion. Nevertheless, the photochemical extrusion has synthetic limitations as to the reaction scale and in some cases gives a number of side products.The oxidative extrusions at ambient temperature, which are run under PTC conditions,7 often require an excess of oxidizing agent (KMnO4) and do not work well in all cases. The extrusion is thought ot proceed via an intermediate oxidation of the bridging sulfoxy group to a sulfone. For these reasons an electrochemical oxidative SO extrusion was tried. A number of electrochemical oxidations both of the thioether and of the sulfoxy moiety are known.Direct8 and indirect9 electrochemical oxidations have been reported. Moreover, oxidations of thioethers and sulfoxides often yield sulfones as by-products.10 First, the cycloadducts 3 were electrolysed in a medium containing NaCl or NaBr in a mixture of acetic acid in water AcOH¡¾H2O 4 :1 (v/v).11 For such systems it is known that the chloride or bromide ions are oxidized to the corre- J. Chem. Research (S), 1998, 346¡¾347$ Scheme 1 Oxidative cycloaddition of halogenated thiophenes. aFor preparation, see ref. 4 $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. 346 J. CHEM. RESEARCH (S), 1998sponding halogens, which disproportionate in aqueous aceticacid to give hypohalites.12 These are the species responsiblefor the oxidation of the sulfoxides. This could be demon-strated as in a similar case in the literature by replacingsodium halide as electrolyte with sodium sulfate whenno reaction took place.In the electrooxidation using NaClor NaBr as electrolyte [Pt/Pt, 0.1 M NaX, AcOH¡ÓH2O 4:1(v/v)] the desired phthalimides 4 we found as the majorproducts in the early phase of the reaction (up to 15% ofconversion has been achieved) with a small amount ofthe corresponding cyclohexadienes as side products. As thereaction proceeds, however, the reaction mixture becomesmore complex, and a number of products emerge.This canbe attributed to halogenation of the methylidene carbon ato the carbonyl function of the imido moiety. Very slowaddition of bromine to the thiabicyclo[2.2.1]heptene S-oxidesleads to the formation of products identical to those found asside products in the electrooxidation. Thus, a second methodof electrochemical oxidative SO extrusion was studied.It is known that thioethers can be transformed to sulfo-xides directly at platinum electrodes.Moreover, thioacetalsare cleanly oxidatively cleaved to alkanones at suchelectrodes.13 Interestingly, it could be shown that thecycloadducts 3 could be transformed to the correspondingphthalimides 4 under the same conditions [Pt/Pt, CH3CN¡ÓH2O (20 :1 v/v) or dry CH3CN, 0.5 M LiClO4]. In thesereactions the sulfur bridge is oxidized before it is extruded.A sulfone bridge in these molecules is much less stable thanthe corresponding sulfoxy bridge.Although it is believedthat SO2 itself is extruded from the molecules, the gas phaseover the reaction solution has not yet been analysed forSO2. For most systems tried, a satisfactory transformationcould be achieved. Scheme 2 shows a typical example. In allcases a divided cell had to be used. The starting materialsand the products are imides and can be reduced readily atthe cathode. Furthermore, in many cases less material, pro-duct and starting material could be isolated from the anodicchamber with increasing reaction time.Thus, it becamemandatory to shorten reaction times using the same set-up.Moreover, in almost all experiments a gradual blocking ofthe anode was observed. This may be due to oxidized sulfurspecies adsorbing on the electrode.14 To circumvent blockingof the electrode and to shorten the reaction time of theoxidative extrusion, ultrasound was employed. Its use15during electrolysis increases mass transport of the substrateto the electrode and of the product from the electrode inmany cases.16 An increase in current at constant potentialwas noted when using ultrasound.The reaction time of theoxidative SO-extrusion can be shortened without alteringthe product distribution. The electrochemical cell wasimmersed in an ultrasonic bath (Bandelin SonoreperRK 510H). Typically, reaction times could be shortened by30% (e.g. from 6 to 4 h). The yield of 4a was increased to87% upon application of sonication.ExperimentalOxidative Cycloaddition of Halogenated Thiophenes with Phenyl-maleimides.A mixture of 2,5-dibromothiophene 1b (2.42 g,10 mmol), N-phenylmaleimide 2a (1.8 g, 10.4 mmol), and m-chloro-perbenzoic acid (7.3 g, 60 weight %, 25.4 mmol) in dichloro-methane 60 cm3) was reuxed for 48 h.Thereafter the solution wascooled, the precipitate formed ltered o, and the ltrate dilutedwith dry diethyl ether (100 cm3). A second crop of crystallineprecipitate formed and was ltered o.Further concentration ofthe ltrate in vacuo and addition of ether (100 cm3) yielded furtherprecipitate. The combined precipitate was washed with ether(220 cm3) and dried. An analytical sample was recrystallized fromdry ether to give 3b as a pale yellow solid (1.73 g, 42%), mp 254 8C;IR (KBr) ~/cm£¾1=3100, 3062, 2858, 1720, 1494, 1390, 1205, 1130,963, 757, 733, 696, 682, 668. 1H NMR (250 MHz, CDCl3): 4.27(2 H, s), 6.52 (2 H, s), 7.19¡Ó7.22 (2 H m, aromatic H), 7.42¡Ó7.47(3 H, m, aromatic H). 13C NMR (62.9 MHz, CDCl3): 52.78,72.18, 126.25, 129.27, 130.92, 132.79, 135.10, 170.09 (C1O).MS (FAB, 3-nitrobenzyl alcohol): m/z (%) 434 ([81Br2]MH,2.5), 432 ([79Br81Br]MH, 4.1), 430 ([79Br2]MH, 2.1), 394([79Br81Br]MH £¾ SO, 1.5). HRMS (FAB, 3-nitrobenzyl alcohol)(C14H9Br2NO3S H): (81Br2MH) 433.8708 (calc.), 433.8698(found); ([79Br81Br]MH) 431.8728 (calc.), 431.8729 (found);(79Br2MH) 429.8748 (calc.), 429.8746 (found).Electrochemical SO-Extrusion.Typically, a solution of a tetra-bromothiabicyclo[2.2.1]heptene S-oxide (3c, 100 mg, 0.17 mmol)in acetonitrile¡Ó5 volume % water (16 cm3) containing LiClO4(0.5 M, 8 mmol) was electrolysed in a divided cell equipped with aplatinum-sheet anode (21 cm2) at a constant current of 6 mA[cathode compartment: palladium-sheet cathode (21 cm2), CH3CN¡Ó10 volume % water (16 cm3), 0.5 M LiClO4].The electrolysis wascontinued until most of the starting material had been consumed(TLC, until about 4.2 F mol£¾1 were passed). Then the anolyte wasconcentrated in vacuo, ether (15 cm3) was added and the precipitateltered o.The ltrate was dried over MgSO4 and concentrated invacuo. The residue was chromatographed on silica gel (eluent:chloroform) to yield N-phenyltetrabromophthalimide 4a (66 mg,72%) as colorless crystals, mp 278 8C (lit.,17 280 8C); IR (KBr)~/cm£¾1= 1705, 1490, 1385, 1335, 1277, 1122, 753, 735, 688, 663.The groups from Coimbra, Portugal, and from Coventry,UK, are grateful to the European Community for nancialsupport of this work (no.CHRX CT94 0475).Received, 3rd November 1997; Accepted, 2nd March 1998Paper E/7/07882JReferences1 K. Torssell, Acta Chem. Scand., Ser. B, 1976, 30, 353.2 A. M. Naperstkow, J. B. Macaulay, M. J. Newlands and A. G.Gallis, Tetrahedron Lett., 1989, 30, 5077.3 Y. Li, T. Thiemann, T. Sawada and M. Tashiro, J. Chem. Soc.,Perkin Trans. 1, 1994, 2323.4 Y. Li, M. Matsuda, T. Thiemann, T. Sawada, S. Mataka andM. Tashiro, Synlett, 1996, 461; Y.Li, T. Thiemann, T. Sawada,S. Mataka and M. Tashiro, J. Org. Chem., 1997, 62, 7926.5 P. Pouzet, I. Erdelmeier, P. Ginderow, J. P. Mornon, D. M.Dansette and D. Mansuy, J. Chem. Soc., Chem. Commun., 1995,473.6 C. Thiemann, T. Thiemann, Y. Li, T. Sawada, Y. Nagano andM. Tashiro, Bull. Chem. Soc. Jpn., 1994, 67, 1886.7 D. Scholz, Monatsh. Chem., 1981, 112, 241; D. G. Lee andN. Srinivasan, Sulfur Lett., 1982, 1, 1.8 E. Fichter and F. Braun, Ber. Dtsch. Chem. Ges., 1910, 43, 3422.9 C. F. Bennett and D. W. Goheen, US Pat., 3 418 224, 1968(Chem. Abstr., 1969, 70, 43434 g).10 D. S. Houghton and A. A. Humray, Electrochim. Acta, 1972,17, 1421; A. A. Humray and D. S. Houghton, Electrochim.Acta, 1972, 17, 1435.11 K. Uneyama and S. Torii, Tetrahedron Lett., 1971, 329; S. Torii,K. Uneyama, K. Iida and K. Sasaki, Tetrahedron Lett., 1972,4513.12 M. Eigen and K. Kustin, J. Am. Chem. Soc., 1962, 84, 1355.13 M. Kimura, H. Kusai and Y. Sasaki, Electrochim. Acta, 1997,42, 497.14 L. R. Moraes, M. Weber and F. C. Nart, Electrochim. Acta,1997, 42, 617.15 See D. Walton and V. S. Phull, Adv. Sonochem., 1996, 4, 205.16 F. Marken, R. G. Compton, S. Savies, S. Bull, T. Thiemann,M. L. Sa e Melo, A. S. Campos Neves, J. Castillo, G. Jung andA. Fontana, J. Chem. Soc., Perkin Trans. 2, 1997, 2055 and refstherein.17 D. S. Pratt and C. O. Young, J. Am. Chem. Soc., 1918, 40, 1415.Scheme 2 Electrochemical SO-extrusionJ. CHEM. RESEARCH (S), 1998 347

ISSN:0308-2342    

DOI:10.1039/a707882j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

An Expeditious Synthesis of Flavones on Montmorillonite K 10 Clay with Microwaves$% Rajender S. Varma,* Rajesh K. Saini and Dalip Kumar Department of Chemistry and Texas Regional Institute for Environmental Studies (TRIES), Sam Houston State University, Huntsville, TX 77341-2117, USA A manipulatively simple and rapid method for the synthesis of flavones is described via a solid-state dehydrative cyclization of o-hydroxydibenzoylmethanes on a clay surface using microwaves. Flavonoids are a group of naturally occurring phenolic compounds widely distributed in the plant kingdom, the most abundant being the �Pavones.Members of this class have been shown to display a wide variety of biological activities1 and have proven useful in the treatment of var- ious diseases.2 There are number of methods available for the synthesis of �Pavones and their analogues,3a�}e including the Allan�}Robinson synthesis,3c synthesis from chalcones4 and via an intramolecular Wittig strategy.5 The most com- mon method, however, involves the Baker�}Venkataraman rearrangement6,7 wherein o-hydroxyacetophenone is benzoy- lated to form the benzoyl ester which is treated with base (pyridine/KOH) to e€ect an acyl group migration, forming a 1,3-diketone.The ensuing diketone is then cyclized under strongly acidic conditions using acetic acid and sulfuric acid to deliver the �Pavone. Consequently, there is a need for the development of a milder protocol for the cyclization process.Clay-catalysed organic reactions have generated consider- able interest in recent years in view of their inexpensive nature and special catalytic attributes under heterogeneous reaction conditions.7 Microwave (MW) heating is used for a wide variety of organic reactions and has found application in rapid and cleaner synthesis of organic compounds.8�}11 More recently, the emphasis has shifted in favor of micro- wave-assisted methods under solvent-free conditions9�}11 which have special appeal as they provide an opportunity to work with open vessels, thus avoiding the risk of high pressure development.Further, this approach enhances the possibility of upscaling the reactions on a preparative scale. In continuation of our studies on microwave-accelerated solvent-free reactions on mineral solid supports,10 we now report a manipulatively simple and rapid microwave protocol for the solid-state cyclodehydration of o-hydroxy- dibenzoylmethanes to �Pavones on a clay surface.The method in its entirety involves the microwave irradiation of o-hydroxydibenzoylmethanes adsorbed on montmorillonite K 10 clay for 1�}1.5 min (bulk temperature of alumina bath reaches 80�}120 8C). The exclusive for- mation of cyclized �Pavones 2a�}g occurs which are easily extractable in good yields from the support (Table 1). The alumina bath, in addition to being a container for the reac- tion vessel, also serves as a heat sink for the microwaves in view of the small amount of reactants normally employed. Among the various other mineral supports explored, namely silica gel, neutral or basic alumina, the formation of �Pavone is ideally accomplished on K 10 clay; some reaction does occur on neutral alumina and silica surfaces but it is not complete.In conclusion, we have developed a simple and mild method for the solid-state cyclodehydration of o-hydroxy- dibenzoylmethanes to �Pavones on a clay surface using microwave irradiation.Experimental Mps are uncorrected. 1H NMR spectra were recorded in CDCl3 solutions at 60 MHz, using TMS as an internal standard. o-Hydroxydibenzoylmethanes 1a�}g were obtained by rearrange- ment of the corresponding o-benzoyloxyacetophenones.13 A Sears Kenmore household microwave oven operating at 2450 MHz was used at its full power, 900 W, for all the experiments. Products were identiRed by comparison of their mp, IR and NMR spectra with those of authentic samples.Typical Procedure: 4'-Methyl-6-methoxy�Pavone 2f.D1-(2-Hydroxy- 5-methoxyphenyl)-3-(4-methylphenyl)propane-1,3-dione 1f (0.2 g, 0.70 mmol) was dissolved in a small amount of dichloromethane (1 ml) and adsorbed on montmorillonite K 10 clay (1.0 g). The contents, in a test-tube, were placed in an alumina bath inside the microwave oven and irradiated for 1.5 min. The crude product was extracted in dichloromethane (215 ml) and then crystallized from methanol to a€ord 2f in 80% yield, mp 161�}162 8C; 1H NMR (CDCl3) 2.26 (3 H, s, C4'�}CH3), 3.36 (3 H, s, C6-OCH3), 6.26 (1 H, s, C3�}H), 6.53�}7.33 (7 H, m, aromatic H); m/z 266 (100%).That the e€ect may not be purely thermal14 is supported by the fact that the reaction could not be completed (65%) in 24 h at the same bulk temperature of 80 8C using an alternate mode of J. Chem. Research (S), 1998, 348�}349$ Scheme Table 1 Synthesis of flavones from o-hydroxydibenzoylmethanes on claya mp (8C) Entry R1 R2 Yield (%) Observed Reported 2a H H 75 96 953b 2b H CH3 77 108�}109 1103d 2c H OCH3 76 155�}157 156�}1573d 2d H NO2 78 244�}245 246�}2473d 2e OCH3 H 73 161 163�}1643e 2f OCH3 CH3 80 161�}162 �} 2g OCH3 OCH3 72 193�}194 19512 aMW irradiated for 1 min (the bulk temperature of the alumina bath reached 80 8C at full power of the MW oven, 900 W).$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). %Presented in part at the 6th International Conference on Microwave and High frequency Heating, Fermo, Italy, 9�}13th September, 1997. *To receive any correspondence (e-mail: chm_rsv@shsu.edu). 348 J. CHEM. RESEARCH (S), 1998heating (oil-bath). The temperature of the reaction mixture inside the alumina bath reached 180 8C after 1 min of irradiation in a MW oven operating at full power of 900 W.We are grateful to Texas Advanced Research Program (ARP) in chemistry (Grant No. 003606-023) and TRIES, Oce of Naval Research/SERDP (Grant No. N00014-96-1- 1067) for Rnancial support. Received, 22nd December 1997; Accepted, 26th February 1998 Paper E/7/09146J References 1 A. F. Welton, L. D. Tobias, C. Fiedler-Nagy, W. Anderson, W. Hope, K. Meyers and J. W. Co€ey, in Plant Flavonoids in Biology and Medicine, ed. V. Cody, E. Middelton Jr and J. B. Harborne, Alan R. Liss, New York, 1986, p. 231. 2 B. Havsteen, Biochem. Pharmacol., 1983, 32, 1141. 3 (a) H. Wagner and L. Farkas, in The Flavonoids, ed. J. Harborne, T. J. Mabry and H. Mabry, Academic Press, New York, 1975, p. 127; (b) A. Banerji and N. Goomer, Synthesis, 1980, 874; (c) J. Allan and R. Robinson, J. Chem. Soc., 1924, 20, 2192; (d ) M. S. Khanna, O. V. Singh, C. P. Garg and R. P. Kapoor, J. Chem. Soc., Perkin Trans. 1, 1992, 2565; (e) J. H. Looker and W. W. Hanneman, J. Org. Chem., 1962, 27, 381. 4 Y. Hoshino, T. Oohinata and N. Takeno, Bull. Chem. Soc. Jpn., 1986, 59, 2351. 5 Y. LeFloc'h and M. LeFeuvre, Tetrahedron Lett., 1986, 27, 2751. 6 W. Baker, J. Chem. Soc., 1933, 1381; H. S. Mahal and K. Venkataraman, J. Chem. Soc., 1934, 1767. 7 M. Balogh and P. Laszlo, Organic Chemistry Using Clays, Springer, Berlin, 1993; J. Chisem, I. C. Chisem, J. S. Rafelt, D. J. Macquarrie and J. H. Clark, Chem. Commun., 1997, 2203. 8 S. Caddick, Tetrahedron, 1995, 51, 10403. 9 R. S. Varma, in Microwaves: Theory and Application in Material Processing IV, ed.D. Clark, W. Sutton and D. Lewis, American Ceramic Society, Ceramic Transactions, 1997, vol. 80, pp. 357�} 365. 10 R. S. Varma, M. Varma and A. K. Chatterjee, J. Chem. Soc., Perkin Trans. 1, 1993, 999; R. S. Varma, A. K. Chatterjee and M. Varma, Tetrahedron Lett., 1993, 34, 3207; R. S. Varma, J. B. Lamture and M. Varma, Tetrahedron Lett., 1993, 34, 3029; R. S. Varma, A. K. Chatterjee and M. Varma, Tetrahedron Lett., 1993, 34, 4603; R.S. Varma and R. K. Saini, Tetrahedron Lett., 1997, 38, 2623; R. S. Varma and R. Dahiya, Tetrahedron Lett., 1997, 38, 2043; R. S. Varma and H. M. Meshram, Tetrahedron Lett., 1997, 38, 5427, 7973; R. S. Varma, R. Dahiya and S. Kumar, Tetrahedron Lett., 1997, 38, 2039, 5131; R. S. Varma and R. K. Saini, Synlett, 1997, 857; R. S. Varma, R. K. Saini and H. M. Meshram, Tetrahi, Tetrahedron Lett., 1997, 38, 7029, 7823, 8819; R. S. Varma and R. K. Saini, Tetrahedron Lett., 1997, 38, 4337; R. S. Varma and R. Dahiya, Tetrahedron Lett., 1998, 39, 1307; R. S. Varma and R. K. Saini, Tetrahedron Lett., 1998, 39, 1481; R. S. Varma and K. P. Naicker, Molecules Online, 1998, 2, 94. 11 J. M. Lerestif, L. Toupet, S. Sinbandhit, F. Tonnard, J. P. Bazureau and J. Hamelin, Tetrahedron, 1997, 53, 6351; A. L. Marrero-Terrero and A. Loupy, Synlett, 1996, 245; A. Benalloum, B. Labiad and D. Villemin, J. Chem. Soc., Chem. Commun., 1989, 386. 12 Dictionary of Organic Compounds, Chapman and Hall, New York, 5th Edn., 1985, p. 159. 13 Vogel's Text Book of Practical Organic Chemistry, ed. B. S. Furniss, A. J. Hannaford, V. Rogers, P. W. G. Smith and A. R. Tatchell, Longman, Harlow, 4th edn., 1987, p. 925. 14 K. D. Raner, C. R. Strauss, F. Vyskoc and L. Mokbel, J. Org. Chem., 1993, 58, 950. J. CHEM. RESEARCH (S), 1998 349

ISSN:0308-2342    

DOI:10.1039/a709146j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Reductive Cleavage of the Se¡ÓSi Bond inArylselenotrimethylsilanes: Novel Method forthe Synthesis of Unsymmetrical Selenides$Songlin Zhang and Yongmin Zhang*Department of Chemistry, Hangzhou University, Hangzhou, 310028, P.R. ChinaArylselenotrimethylsilanes are reduced by samarium diiodide to yield samarium areneselenolates, which react with alkylhalides to give unsymmetrical selenides.As a powerful and versatile one-electron transfer reducingand coupling reagent, SmI2 has been applied widely inorganic synthesis.1¡Ó3 Our previous work on the reductivecleavage of S¡ÓS, Se¡ÓSe and Te¡ÓTe bonds with SmI24.5 ledus to investigate the reductive cleavage of Se¡ÓSi bonds bySmI2.Selenides are involved in important transformationssuch as the synthesis of alkanes,6¡Ó8 alkenes,9¡Ó11 and alkylhalides,12,13 but relatively few syntheses of selenides havebeen described. A useful approach to the synthesis ofselenides is based on the alkylation of selenide ion, whichcan easily be prepared from elemental selenium by reductionwith sodium in liquid ammonia,14 sodium tetrahydroboratein ethanol15 or water16 or with tetraalkylammonium tetra-hydroborates.17 In another approach, alcohols and selenolswere treated with acid to give selenides.18 Most of thesemethods have been applied successfully to the synthesis ofselenides.Here we report that SmI2 reduces arylselenotrimethyl-silanes to samarium areneselenolates under a nitrogen atmo-sphere.This new selenolate anion species reacts with alkylhalides to give unsymmetrical selenides in good yield underneutral conditions (Scheme 1).In summary, a novel method for the preparation ofunsymmetrical selenides has been elucidated, the advantagesof which are simple manipulation, mild and neutralconditions.ExperimentalGeneral Procedure.A solution of arylselenotrimethylsilane19(1 mmol) in THF (1 ml) was added by syringe to a deep bluesolution of SmI2 (2.2 mmol) in THF (10 ml) at reux temperatureunder a nitrogen atmosphere.The deep blue solution graduallybecame brown within 3 h, which showed that the Se¡ÓSi bond hadbeen reductively cleaved by SmI2 and that the samarium arene-selenolate (ArSeSmI2)20 had been generated. Alkyl halides (1 mmol)in THF (1 ml) were then added by syringe and stirred at reuxingtemperature for 3 h. A dilute solution of HCl and diethyl etherwas added. The organic layer was washed with water (20 ml2)and dried over anhydrous Na2SO4. The solvent was removedin vacuo.The crude product was puried by preparative TLC onsilica gel (cyclohexane as eluent). Some results are summarized inTable 1.1.20 mp 34¡Ó35 8C, dH (CCl4) 3.93 (2 H, s), 7.00¡Ó7.40 (10 H, m);~max/cm£¾1 3100, 3080, 3040, 2950, 1610, 1590, 1500, 1485, 1460,1440, 1180, 1080, 1020, 1000, 910, 760, 740, 660, 6002.21 Oil, dH (CCl4) 0.80 (3 H, t), 1.07¡Ó1.60 (12 H, m), 2.75 (2 H,t), 7.00¡Ó7.50 (5 H, m); ~max/cm£¾1 3100, 3080, 2980, 2980¡Ó2940,2870, 1590, 1485, 1460, 1440, 1380, 1075, 1020, 1000, 730, 690, 660.3.22 Oil, dH (CCl4) 0.80 (3 H, t), 1.07¡Ó1.57 (16 H, m), 2.77 (2 H,t), 7.00¡Ó7.60 (5 H, m); ~max/cm£¾1 3100, 3080, 2980, 2960¡Ó2940, 2870,1590, 1486, 1440, 1380, 1080, 1020, 1000, 730, 690, 665.4.10 Oil, dH (CCl4) 0.82 (3 H, t), 1.07¡Ó1.60 (20 H, m), 2.77 (2 H,t), 7.00¡Ó7.60 (5 H, m); ~max/cm£¾1 3100, 3080, 2980, 2960¡Ó2940,2870, 1590, 1485, 1470, 1440, 1380, 1080, 1020, 1000, 730, 690, 660.5.23 mp 33¡Ó34 8C, dH (CCl4) 0.80 (3 H, t), 1.07¡Ó1.60 (28 H, m),2.77 (2 H, t), 7.00¡Ó7.60 (5 H, m); ~max/cm£¾1 3100, 3080, 2980,2960¡Ó2940, 2870, 1590, 1485, 1470, 1440, 1075, 1020, 1000, 730,690, 665.6.24 Oil, dH (CCl4) 2.20 (3 H, s), 3.87 (2 H, s), 6.83¡Ó7.40 (9 H,m); ~max/cm£¾1 3100, 3080, 3040, 2990, 2950, 2870, 1600, 1500, 1470,1460, 1385, 1270, 1200, 1180, 1040, 820, 760, 690, 650, 600.7.25 Oil, dH (CCl4) 2.30 (3 H, s), 2.54 (3 H, s), 6.90¡Ó7.40 (4 H,m); ~max/cm£¾1 3100, 3080, 2980, 2950, 2870, 1595, 1485, 1470, 1440,1380, 1040, 735, 650.8.25 Oil, dH (CCl4) 1.30 (3 H, t), 2.30 (3 H, s), 2.73 (2 H, q),6.91¡Ó7.45 (4 H, m); ~max/cm£¾1 3100, 3080, 2980, 2960, 2870, 1590,1485, 1470, 1440, 1380, 1040, 730, 690, 660.9.25 Oil, dH (CCl4) 1.36 (6 H, d), 2.30 (3 H, s), 3.01¡Ó3.08 (1 H, m)6.90¡Ó7.40 (4 H, m); ~max/cm£¾1 3100, 3080, 2980¡Ó2960, 2870, 1590,1485, 1470, 1440, 1380, 1040, 730, 690, 665.1H NMR spectra were recorded on a PMX-60 MHZ instru-ment (TMS as internal reference), IR spectra on a PE-683 spec-trometer.J. Chem.Research (S),1998, 000¡Ó000$Scheme 1Table 1 Yields of the products ArSeREntry Ar R¡ÓX Product Yielda (%)a Ph PhCH2Clb 1 PhSeCH2Ph 84b Ph PhCH2Brb 1 PhSeCH2Ph 84c Ph CH3(CH2)7Br 2 PhSe(CH2)7CH3 80d Ph CH3(CH2)9Br 3 PhSe(CH2)9CH3 77e Ph CH3(CH2)11Br 4 PhSe(CH2)11CH3 79f Ph CH3(CH2)15Br 5 PhSe(CH2)15CH3 75g o-CH3C6H4 PhCH2Clb 6 o-CH3C6H4SeCH2Ph 82h o-CH3C6H4 PhCH2Brb 6 o-CH3C6H4SeCH2Ph 82i o-CH3C6H4 CH3I 7 o-CH3C6H4SeCH3 80j o-CH3C6H4 CH3CH2I 8 o-CH3C6H4SeCH2CH3 76k o-CH3C6H4 CH3CH(Br)CH3 9 o-CH3C6H4SeCH(CH3)2 68aOf isolated product. b Alkylation at room temperature for 4 h.We are grateful to the National Natural ScienceFoundation of China and Laboratory of OrganometallicChemistry, Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences, for nancial support.$This is a Short Paper as dened 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.350 J. CHEM. RESEARCH (S), 1998Received, 22nd December 1997; Accepted, 9th March 1998 Paper E/7/09124I References 1 P. Girard, J. L. Namy and H. B. Kagan, J. Am. Chem. Soc., 1980, 102, 2693. 2 G. A. Molander, Chem. Rev., 1992, 92, 29. 3 G. A. Molander and C. R. Harris, Chem. Rev., 1996, 96, 307. 4 S. X. Jia and Y. M. Zhang, Synth. Commun., 1994, 24, 787. 5 Y. M. Zhang, Y. P. Yu and R. H. Lin, Synth.Commun., 1993, 23, 189. 6 M. Sevrin, D. Van Ende and A. Krief, Tetrahedron Lett., 1976, 30, 2643. 7 W. Dumont, P. Bayet and A. Krief, Angew. Chem., Int. Ed. Engl., 1974, 13, 804. 8 D. Seebath and A. K. Beck, Angew. Chem. Int. Ed. Engl., 1974, 13, 804. 9 D. N. Jones, D. Mundy and R. D. Whitehouse, Chem. Commun., 1970, 86. 10 K. B. Sharpless and M. W. Young, J. Org. Chem., 1975, 40, 947. 11 S. Halazy and A. Krief, Tetrahedron Lett., 1979, 49, 4233. 12 M. Sevrin and A.Krief, Tetrahedron Lett., 1976, 30, 2647. 13 M. Sevrin and A. Krief, J. Chem. Soc., Chem. Commun., 1980, 2, 656. 14 D. Linotta, W. Markiewicz and H. Santiesteben, Tetrahedron Lett., 1977, 50, 4365. 15 D. L. Klayman and T. S. Gri�n, J. Am. Chem. Soc., 1973, 95, 197. 16 J. Bergman and L. Engman, Org. Prep. Proced. Int., 1978, 10, 289. 17 J. Bergman and L. Engman, Synthesis, 1980, 7, 569. 18 M. Clarembeau and A. Krief, Tetrahedron Lett., 1984, 25, 3625. 19 M. R. Detty, J. Org. Chem., 1979, 44, 4528. 20 S. I. Fukuzawa, Y. Niimoto, T. Fujinami and S. Sakai, Heteroat. Chem., 1990, 1, 491. 21 G. Pandey, B. B. V. Soma Sekhar and U. T. Bhalerao, J. Am. Chem. Soc., 1990, 112, 5650. 22 A. Krief, W. Dumont, J. Noel, G. Everard and B. Norbery, J. Chem. Soc., Chem. Commun., 1985, 569. 23 A. Toshimitsu, H. Owada, S. Uemura and M. Okano, Tetrahedron Lett., 1980, 21, 5037. 24 G. Paul and T. M. Aellen, J. Chem. Soc. Chem. Commun., 1980, 558. 25 A. D. Baker, G. H. Armen and G. D. Yang, J. Org. Chem., 1981, 46, 4127. J. CHEM. RESEARCH (S), 1998 3

ISSN:0308-2342    

DOI:10.1039/a709124i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Enamine-induced Ring Transformations of 6-Substituted 5-Formyl-1,3-dimethyluracils$ Harjit Singh,* Dolly, Swapandeep Singh Chimni and Subodh Kumar* Department of Chemistry, Guru Nanak Dev University, Amritsar-143 005, India 5-Formyl-1,3,6-trimethyluracil 1 undergoes facile ring transformation with enamines under acidic conditions to provide 1-heteroaroyl-1,3-dimethylurea derivatives. Uracil derivatisation at each of its reactive sites has attained paramount signi®cance in potential medicinal target com- pounds.1 The nucleophile-induced modi®cations of uracil and its derivatives emanating from their reactions at C(5) and/or C(6) or at an electrophilic appendage at C(5) make use of relatively strong nucleophiles, viz.amines, hydrazines, cyanide ion, etc. or of strongly basic reaction conditions (NaOH, NaOEt, BuLi, etc.).2±6 The steric bulk of a methyl group at C(6) of uracil, in general, slows down or com- pletely restricts nucleophilic addition at C(6) and causes alternative reactions due to generation of an anion4b,7 at CCH3.Recently, we have reported8 that 5-formyl-1,3- dimethyluracil reacts with enamines, even under acidic con- ditions, to provide unique annulation products. We envi- saged that in the reactions of enamines with 5-formyl-1,3,6- trimethyluracil under acidic conditions9 the probability of generation of an anion at the 6-CH3 carbon would be low and annulation might constitute the major mode of reaction. Hence, the reactions of 5-formyl-1,3,6-trimethyluracil 1 with enamines have been studied. 5-Formyl-1,3,6-trimethyluracil 1 on reaction with 3-amino- 5,5-dimethylcyclohex-2-enone 2 in re�uxing acetonitrile± TFA solution gives a product (50%), mp 92 8C. The parent ion peak at m/z 303 (Má) in its mass spectrum shows it to be a condensation product of 1 and 2. In its 1H NMR spectrum the appearance of one Me signal as a doublet (d 2.99, J 4.8 Hz) and other Me units as singlets points towards the N(1)0C(6) ring opening of the uracil moiety and a 1 H singlet at d 8.07 shows the presence of the aromatic ring.From these spectral data and the elemental analysis the structure 3 is proposed for this compound. Therefore, 1 undergoes ring transformation with enamines and the 6-Me of 1 does not participate in the reaction (Scheme 1). Similarly, compound 1 reacts with 6-amino-1,3-dimethyl- uracil 4 and 3-aminobut-2-enenitrile 6 in re�uxing acetonitrile±TFA solution to give ring transformation products 5 (80%), mp 180±182 8C, Má at m/z 319 and 7 (8%), mp 120±125 8C, Má at m/z 246, respectively.Therefore, despite the presence of a methyl group, com- pound 1 reacts with enamines through attack at CHO with subsquent annulation at C(6) but the area unit is eliminated and after annulation the uracil ring is opened. We argued that if uracil is substituted at C(6) with Cl, a leaving group, the formation of annulation products with intact uracil units could be facilitated.The reaction of compound 8 with 4 in re�uxing acetonitrile±TFA solution gives annulation product 9, mp 300±310 8C, Má at m/z 303. However, ethyl b-amino/anilino crotonates 10 with 8 provide respective 6-anilino-5-formyl- uracils 11a (70%), mp 222 8C (lit.,10 225 8C) and 11b (45%), mp 180 8C, Má at m/z 259 and corresponding ring- transformed products are not formed (Scheme 2). The formation of compounds 3, 5 and 7 could be rationalised through the initial nucleophilic attack of enamine at CHO to give intermediate 12 which subsequently through intramolecular attack of NH2 at C(6) of uracil provides ring-transformed products6,8 3, 5, 7.The well documented reversibility11 of nucleophilic attack of amines, thiols, alcohols etc. at C(6) of uracil and higher reactivity of formyl than C(6) carbon rule out the possibility of alter- native initial attack of amine nitrogen at C(6) of 1. Also, as J. Chem. Research (S), 1998, 352±353$ Scheme 1 Scheme 2 $This is a Short Paper as de®ned 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. 352 J. CHEM. RESEARCH (S), 1998the electron-withdrawing ability of the substituent (R1) atthe b position of the enamine increases, the nucleophilicityof enamine NH2 and consequently the yield of the ring-transformation product [CON (80%), CO (50%), CN (8%)]decreases. Further in the case of reactions of 5-formyl-1,3-dimethyluracil with these enamines, the formation ofdihydropyridines through intermediate 14 occurs8 but whenMe is present at C(6), the intermediate 13 does notform dihydropyridine derivatives.It has been found that5-vinyluracil and 6-methyl-5-vinyluracils have cis- and trans-diene congurations, respectively, which the intermediates13 and 14 would respectively acquire. In intermediate 13 thesteric bulk of the Me group probably restricts the attack ofenamine and respective dihydropyridine derivatives are notformed (Scheme 3).Thus, 5-formyl-1,3,6-trimethyluracil 1 undergoes facilering tranformations with enamines under acidic conditionsto provide carbamoylpyridine derivatives, and the methylat C(6) does not contribute 6-CH2£¾ induced annulationreactions and rather restricts the usual Hantszch-typedihydropyridine formation reactions of the 5-formyl group.ExperimentalMelting points were determined in capillaries and are uncorrected.1H and 13C NMR spectra were run on a Bruker AC200 MHzinstrument using TMS as an internal standard. Mass, infraredand UV spectra were recorded on Shimadzu GCMS-QP-2000,Philips Scientic SP3-300 and Shimadzu UV-240 spectrometers,respectively.Elemental analyses of solid samples were performedat the microanalytical laboratory of the Regional SophisticatedInstrumentation Centre, Chandigarh.Reactions of 5-Formyluracils 1, 8 with Enamines: General Procedure.A solution of compound 1 or 8 (1.00 g, 5.95 mmol), enamine(2 equivalent, 12 mmol) in CH3CN (10 ml) containing TFA (0.1 ml)was reuxed.The progress of the reaction was monitored by TLCand after completion (5¡Ó6 h) the solvent was distilled o. Theresidue was chromatographed on a silica gel column using hexane¡Óethyl acetate mixtures as eluents.Compound 3.Yield 50%, mp 92 8C, M+ at m/z 303 (EtOH);1H NMR (CDCl3) 1.14 (s, 6 H, 2CH3), 2.58 (s, 4 H, 2CH2),2.99 (d, J 4.8 Hz, 3 H, NHCH3), 3.02 (s, 3 H, CH3), 3.09 (s,3 H, CH3), 8.07 (s, 1 H, C1CH), 9.03 (br, 1 H, NH); 13C NMR(CDCl3) (Normal/DEPT-135) 22.72 (ve, CH3), 27.04 (ve,CH3), 26.23 (ve, CH3), 34.15 (ve, CH3), 46.22 (£¾ve, CH2), 51.75(£¾ve, CH2), 131.52 (ve, CH), 124.60 (absent), 131.53 (absent),154.60 (absent), 156.42 (absent), 162.55 (absent), 172.15 (absent),196.36 (absent); IR (KBr) ~max 1660 (C1O), 1600 (C1O),1700 cm£¾1 (C1O).(Found: C, 63.5; H, 6.6; N, 13.8.C16H21N3O3requires C, 63.37; H, 6.93; N, 13.86%).Compound 5.Yield 80%, mp 180¡Ó182 8C (EtOH), M at m/z319; 1H NMR (CDCl3) 2.56 (s, 3 H, CH3), 3.10 (s, 3 H, CH3),3.30 (s, 3 H, CH3), 3.47 (s, 3 H, NCH3), 3.71 (d, J 4.63 Hz, 3 H,NHCH3), 8.25 (s, 1 H, 1CH); 13C NMR (CDCl3) (Normal/DEPT-135) 25.10 (ve, CH3), 28.43 (ve, NCH3), 29.49 (ve,NCH3), 34.38 (ve, NCH3), 39.36 (ve, NCH3), 134.93 (ve, CH),106.43 (absent), 107.95 (absent), 127.28 (absent), 134.97 (absent),154.97 (absent), 160.17 (absent), 164.6 (absent), 171.17 (absent);IR (KBr) ~max 1610 (C1O), 1700 cm£¾1 (C1O) (Found: C, 51.9;H, 5.24; N, 21.3.C14H17N5O4 requires C, 52.66; H, 5.37;N, 21.94%).Compound 7.Yield 8%, mp 120¡Ó125 8C (EtOH), M at m/z246; 1H NMR (CDCl3) 2.58 (s, 3 H, CH3), 2.79 (s, 3 H, CH3),2.96 (d, J 4.8 Hz, 3 H, NHCH3), 3.09 (s, 3 H, NCH3), 7.72 (s,1 H, 1CH); 13C NMR (CDCl3) (Normal/DEPT-135) 22.76 (ve,CH3), 23.58 (ve, CH3), 27.12 (ve, NCH3), 34.07 (ve, NCH3),106.74 (absent), 115.99 (absent), 129.59 (absent), 136.67 (ve, CH),154.66 (absent), 157.41 (absent), 162.19 (absent), 171.02 (absent);IR (KBr) ~max 1661 (C1O), 1690 (C1O), 2240 cm£¾1 (C2N).Compound 9.Yield 80%, mp 300¡Ó310 8C (CHCl3¡Óhexane), Mat m/z 303MR (CDCl3) 3.49 (s, 6 H, 2NCH3), 3.75 (s,6 H, 2NCH3), 9.18 (s, 1 H, CH); 13C NMR (CDCl3) 28.71(q NCH3), 30.15 (q, NCH3), 96.20 (s, >C<), 106.52 (s, >C<),139.73 (d, CH), 172.6 (s, C1O), 193 (s, C1O); IR (KBr) ~max 1660(C1O), 1600 cm£¾1 (C1C) (Found: C, 50.74; H, 4.02; N, 24.68%.C13H13N5O4 requires C, 51.48; H, 4.29; N, 23.10%).We thank the University Grants Commission (India) fornancial assistance.Received, 2nd December 1997; Accepted, 9th March 1998Paper E/7/08683KReferences1 H.Wamho, J. Dzenis and K. Hirota, in Adv. Heterocycl.Chem., 1992, 55, 129; D. J. Brown, in ComprehensiveHeterocyclic ChemistryThe Structure, Reactions, Synthesis andUses Of Heterocyclic Compounds, ed. A. R. Katritzky and C.W.Rees, Pergamon Press, Oxford, 1984, vol. 3, pp. 57¡Ó155.2 E. G. Sander, in Bioorganic Chemistry, ed. E. E. Van Tamelen,Academic Press, New York, 1977, vol. 2, pp. 273¡Ó297 and refs.therein; T. K. Bradshaw and D. W. Hutchinson, Chem. Soc.Rev., 1977, 6, 43.3 H. C. van der Plas, Ring Transformations of Heterocycles,Academic Press, New York, 1975, vol. 1¡Ó2; Tetrahedron, 1985,41, 237.4 K. Hirota, Y. Kitade and S. Senda, (a) J. Chem. Soc., PerkinTrans. 1, 1984, 1859 and refs. therein; (b) J. Org. Chem., 1981,46, 3949.5 S. Kumar, S. S. Chimni, D. Cannoo and J. Singh, Bioorg. Med.Chem., 1995, 3, 891 and refs. therein.6 H. Singh, P. Singh, S. S. Chimni and S. Kumar, J. Chem. Soc.,Perkin Trans. 1, 1995, 2363.7 K. Hirota, K. A. Watanabe and J. J. Fox, J. Org. Chem., 1978,43, 1193; K. Hirota, T. Asao, I. Sugiyama and S. Senda,Heterocycles, 1987, 15, 289; M. Noguchi, K. Sakamoto,S. Nagata and S. Kajigaeshi, J. Heterocycl. Chem., 1988, 25,205; N. Yasue, S. Ishikawa and M. Noguchi, Bull. Chem. Soc.Jpn., 1992, 65, 2845; K. Hirota, Y. Kitade, K. Shimada andY. Maki, J. Org. Chem., 1985, 50, 1512.8 H. Singh, Dolly, S. S. Chimni and S. Kumar, Tetrahedron, 1995,51, 12775.9 Under neutral conditions, enamines fail to react with aldehydes.See also K. Hirota, K. Kubo, H. Sajaki, Y. Kitade, M. Sakoand Y. Maki, J. Org. Chem., 1997, 62, 2999.10 A. Sivaprasad, J. S. Sandhu and J. N. Baruah, Indian J. Chem.,Sect. B, 1985, 24, 305.11 I. H. Pitman, M. J. Cho and G. S. Pork, J. Am. Chem. Soc.,1974, 96, 1840; B. A. Otter, E. A. Falco and J. J. Fox, J. Org.Chem., 1968, 33, 3593.Scheme 3J. CHEM. RESEARCH (S), 1998 353

ISSN:0308-2342    

DOI:10.1039/a708683k

出版商:RSC    

年代:1998

数据来源: RSC