摘要:

Sunlight-induced Regio- and Stereo-specific (2p a 2p) Cycloaddition of Arylethenes to 2-Substituted-1,4-naphthoquinones$ Christopher Covell,a Andrew Gilbert*a and Christoph Richterb aDepartment of Chemistry, The University of Reading, Whiteknights, P.O. Box 224, Reading, Berkshire RG6 6AD, UK bPlataforma Solar de Almer�Ê a, 04200 Tabernas, Almer�Ê a, Spain 2-Acetoxy-1,4-naphthoquinone undergoes photochemical regio- and stereo-specific (2p a 2p) addition to styrene and 1,1-diphenylethene in high yield, whereas the stilbenes yield mainly spirooxetanes: the cyclobutane formation occurs essentially quantitatively in sunlight. Our recent interest in the photochemistry of 1,4-naphtho- quinone has been to elucidate the features which may control the site of addition of ethenes to give spirooxetanes and cyclobutane derivatives.1 Although there is some indi- cation for alkenes that the ease of electron transfer to the quinone is an important aspect, for other ethenes structural e€ects appear to control the site of reaction but not in a wholly predictable manner.The cyclobutane formation could, however, provide a versatile and convenient access to cyclobutene quinones 1, the ring-opened isomer 2 of which has potential in anthracyclinone and pyranoquinone syn- thesis. 1,4-Naphthoquinones 3 with an electron-donor sub- stituent at the 2-position appeared to be suitable for this purpose as formation of the cyclobutane adduct would be favoured over the spirooxetane process because of the increase in the energy of the quinone 3np* state2 and, furthermore, conversion into the cyclobutene moiety may be facilitated.However, the 2-hydroxy-, 2-amino-, and 2-thio-1,4-naphthoquinones undergo (3 a 2) photocyclo- addition to ethenes thereby giving a useful entry to naphtho[2,3-b]furan,3 benz[ f ]indole,4 and naphtho[2,3-b]- thiophene5 derivatives respectively; and cyclobutane adducts from 2-methoxy-1,4-naphthoquinone yield hydroxyoxetanes from a secondary photochemical process.6 Furthermore, 2-halogeno-1,4-naphthoquinones undergo non-selective addition with the ethenes of interest in the present study.7 Our studies to develop a realistic route to cyclobutene quinones have thus focused on the photochemistry of protected 2-hydroxy- and 2-amino-quinones and the recent account by Suginome et al.8 of the photoaddition of 2-acetoxy-1,4-naphthoquinone 4 to 2-methylpropene in benzene solution to give the head-to-head adduct 5 in 41% yield using a Pyrex-Rltered high-pressure mercury arc lamp prompts us to report our Rndings with these systems.The projected application of the cyclobutene quinones from this study necessitated the use of arylethenes as the photo- chemical addends to the quinones, and the facile high-yield access to the required cyclobutanes is illustrated here by the additions of styrene and of 1,1-diphenylethene to the 2-acetoxy derivative (Scheme 1). The initial studies used Pyrex-Rltered radiation from a (medium-pressure mercury arc) on methanol or acetonitrile solutions of the addends.Preliminary spectroscopic analysis of the crude material showed that only the head-to-head isomers 6 and 7 were formed from styrene and 1,1-diphenyl- ethene respectively. Although the crude yields of these photoadducts were in excess of 80%, the need to remove minor impurities by �Pash chromatography reduced the isolated yields to approximately 50%.Detailed NMR spec- tral data of the adduct from 4 and styrene allowed the exp structure 6 (R2=H, R3 = Ph) to be assigned. The head-to- head regiospeciRcity of the adducts is expected from for- mation of the most stable intermediate 1,4-diradical but the observed stereospeciRcity is not common for quinone additions. For example, both the exo and endo cyclobutane isomers are formed from styrene and 1,4-naphthoquinone.1 In contrast to the reaction-mode speciRcity for cyclobutane formation with both styrene and 1,1-diphenylethene, both cis and trans stilbenes gave exclusively spirooxetanes with 2- acetoxy-1,4-naphthoquinone from attack at the 4-carbonyl group and in each case one stereoisomer predominated (>80%).Again, this contrasts with the parent quinone which yields both spirooxetanes and the cyclobutane isomers with the stilbenes.7 Protection of 2-amino-1,4-naphtho- quinone also promotes cyclobutane formation with ethenes in preference to the (3 a 2) photoaddition reported for the parent derivative.4 The proposed route to cyclobutene quinones would only be acceptable as a realistic synthetic procedure if the photo- chemical step giving the cyclobutane adducts could be scaled-up and gave the product with purity suitable for the next step without the need for chromatography. In an attempt to achieve these aims and to ensure that the photo- chemistry would be environmentally acceptable as well as hazard-free, we investigated the sunlight-induced formation of the cyclobutanes from 4 and the arylethenes at the Plataforma de Solar in AlmeroA a.The small-scale reactor at the facility allows cycling and cooling of the reactant solution (1 l) and comprises an exposed borosilicate glass tube (Duran, 1.0 m0.032 m o.d.) at the focal line of a J. Chem. Research (S), 1998, 316�}317$ Scheme 1 $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J.Chem. Research (M). *To receive any correspondence. 316 J. CHEM. RESEARCH (S), 1998compound parabolic collector aluminium mirror which hasan optical concentration of 2. In this apparatus a greaterthan 96% conversion of 4 (10 g) into 6 (R2=H, R3 = Ph)or 7 was achieved in 6 h exposure, and furthermore theadducts were obtained in a high state of purity directlyby rotary evaporation of the solvent (recycled) from thereaction mixture: in particular, the minor by-products usingarticial light were not evident in the high-resolution 1HNMR spectrum of the `crude' material from solar radiation.The concentration of the quinone can be increased to 6%w/v without any adverse eects: this has the advantage ofincreasing the absorption cut-o of the quinone from ca.370 to 430 nm (at absorbance 1.5) in the region of highincrease in solar emission and so producing higher yields ofthe cyclobutane adducts from shorter exposure times.Thephotoaddition is also not inuenced by temperature up to60 8C so that water cooling of the solar-irradiated solutionsis not essential.The solar-induced process has thus given access to multi-gram quantities of the cyclobutane adducts in excellentyields and purities and with a minimum work-up procedure.ExperimentalPhotochemical Methods.(a) Articial irradiation. The photo-chemical source comprised a 125 W medium-pressure mercury arcinside a water-cooled Pyrex immersion well: this was placed in aPyrex vessel containing an acetonitrile solution of the 2-substitutedquinone (0.005 mol) and the arylethene (0.02 mol) under air.Thereaction was monitored by HPLC (10004.6 mm, 5 mm ODScolumn; 20% aqueous acetonitrile eluent). The adducts were puri-ed by ash chromatography using ICN silica 32-63 (Park ScienticLtd.) with ethyl acetate¡Óhexane (1:3) as eluent.(b) Sunlight irradiation. The essential features of this apparatusare briey described above. The reactions were monitored by HPLCand the adducts obtained in essentially quantitative yield and>99% purity by rotary evaporation: the adducts can be recrystal-lised from methanol.Compound 6 (R2=H, R3= Ph).mp 134¡Ó136 8C; dH (400 MHz,CDCl3) 8.27 (1 H, dd, J 7.32, J 0.73), 8.20 (1 H, dd, J 7.32, 0.73),7.83 (2 H, dd), 7.37 (2 H, m, aryl H), 7.29 (3 H, m, aryl H), 3.97(1 H, br overlapping dd, J 9.16, 1.1), 3.62 (1 H, ddd, J 12.46, 5.87,1.1), 3.12 (1 H, ddd, J 13.55, 12.46, 9.16), 2.60 (1 H, ddd, J 13.55,9.16, 5.87 Hz), 2.00 (3 H, s, CH3); dC (100 MHz, CDCl3) 195.77(C1O), 191.84 (C1O), 170.37 (ester C1O), 135¡Ó135 (12 aryl C),81.00, 49.54, 45.43, 28.02, (cyclobutane C), 20.46 (CH3);~max (Nujol)/cm£¾1 1726s, 1687s, 1683s (Found: C, 74.92; H, 5.17.Calc.for C20H16O4: C, 75.04; H, 5.04%); m/z 321.1129, [M H](Calc. for C20H17O4: 321.1127).Compound 7. mp 191¡192 8C; dH (400 MHz, CDCl3) 7.93 (1 H,dd, J 7.70, 0.73), 7.80 (1 H, dd, J 7.33, 1.1), 7.58 (2 H, m, J 7.70,7.32, 1.09, 0.73), 7.49 (2 H, m), 7.35 (3 H, m), 7.222 (2 H, d, J7.32), 6.98 (3 H, overlapping dd), 3.57 (1 H, dd, J 10.62, 4.40), 3.51(1 H, dd, J 12.20, 4.40), 3.43 (1 H, dd, J 12.20, 10.62), 2.12 (3 H, s,CH3); dH (100 MHz, CDCl3) 195.65, 192.34, 170.76, 134.66¡Ó126.41(18 lines), 81.10, 58.55, 48.87, 33.79, 20.78; ~max (Nujol)/cm£¾1 1741s,1695s (Found: C, 78.20; H, 5.20.Calc. for C26H20O4: C, 78.79;H, 5.09%); m/z 397.1447, [M H] (Calc.for C26H21O4:397.1444).This study was carried out under the EU-TMR Pro-gramme Nr. ERB FMGECT 950023.Received, 16th January 1998; Accepted, 11th February 1998Paper E/8/00445EReferences1 D. Bryce-Smith, E. H. Evans, A. Gilbert and H. S. McNeil,J. Chem. Soc., Perkin Trans. 1, 1992, 485.2 See references in, J. M. Bruce, The Chemistry of QuinoidCompounds, ed. S. Patai and Z. Rapport, Wiley, New York,1974, vol. 1, ch. 9; K. Maruyama and A. Osuka, The Chemistryof Quinonoid Compounds, ed. S. Patai and Z. Rapport, Wiley,New York, 1988, vol. 2, ch. 13.3 K. Kobayashi, H. Shimizu, A. Sasaki and H. Suginome, J. Org.Chem., 1991, 56, 3204; 1993, 58, 4614; K. Kobayashi, Y. Kannoand H. Suginome, J. Chem. Soc., Perkin Trans. 1, 1993,1449; H. Suginome, H. Kamekawa, H. Sakurai, A. Konishi,H. Senboku and K. Kobayashi, J. Chem. Soc., Perkin Trans. 1,1994, 471.4 K. Kobayashi, H. Takeuchi, S. Seko, Y. Kanno, S. Kujime andH. Suginome, Helv. Chim. Acta, 1991, 74, 1091; 1993, 76, 2942.5 H. Suginome, K. Kobayashi, A. Konishi, H. Minakawa andH. Sakurai, J. Chem. Soc., Chem. Commun., 1993, 180.6 T. Otsuki, Bull. Chem. Soc. Jpn, 1976, 49, 2596.7 A. Gilbert and P. Kamonnawin, unpublished results.8 H. Senboku, Y. Kajizuka, K. Kobayashi, M. Tokuda andH. Suginome, Heterocycles, 1997, 44, 341.J. CHEM. RESEARCH (S), 1998 317

ISSN:0308-2342    

DOI:10.1039/a800445e

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Convenient Syntheses of Naturally Occurring Angular and Linear Naphthopyrans$ Madhusudan V. Paradkar,* Himanshu M. Godbole, Anup A. Ranade and Augustine R. Joseph Department of Chemistry, Post Graduate & Research Centre, A.G. College, Karve Road, Pune 411 004, India A convenient synthesis of naturally occurring angular naphthopyrans and their 6-demethoxy derivatives is described starting from 2-acetyl-1-naphthols along with the synthesis of linear naphthopyrans from 3-acetyl-2-naphthol. 2,2-Dimethylnaphtho[1,2-b]pyrans like mollugin,1 dihydro lapachenole2 (3a), lapachenole3 (4a) and their 6-demethoxy derivatives4 (3b and 4b) have been isolated from natural sources. Recently 3,4-dihydronaphtho[2,3-b]pyran5 (7a), a linear naphthopyran, has also been isolated from the roots of Withania somnifera. Although a few approaches have been reported for the synthesis of angular naphthopyrans (3a, 3b, 4a and 4b), surprisingly so far no attempt has been made to obtain the linear naphthopyrans (7a, 7b and 8). The reported methods for the synthesis of angular naphthopyrans involve (i) con- densation of 1-naphthol with 3,3-dimethylacrylic acid or its derivatives,3,6�}9 (ii) Claisen rearrangement of the propargyl ether of 1-naphthol,10�}12 (iii) condensation of 1-naphthol with isoprene providing the dihydronaphthopyran13 and (iv) conversion of the corresponding benzocoumarin into the dimethyl pyran ring system using methylmagnesium iodide.7,14 In connection with our interest in the synthesis of various naturally occurring naphthopyrans and their transform- ations into other naturally occurring and biologically active pyranonaphthoquinones, we wanted a common method, applicable for both angular and linear naphthopyrans.Our approaches for the synthesis of naphthopyrans (3a, 3b, 4a, 4b, 7b and 8) are depicted in Schemes 1 and 2. 2-Acetyl-1- naphthol15 (1b) was treated with acetone in the presence of pyrrolidine16 to obtain 3,4-dihydro-2,2-dimethyl-4H- naphtho[1,2-b]pyran-4-one (2b) in 65% yield which on Clemmensen reduction provided 3b and on reduction with NaBH4 followed by acid-catalysed dehydration gave 2,2-dimethylnaphtho[1,2-b]pyran 4b.This strategy was then extended for the synthesis of lapachenole 4a and dihydro- lapachenole 3a from 2-acetyl-l-hydroxy-4-methoxynaphtha- lene 1a via the intermediacy of 2a (Scheme 1). 3-Acetyl-2-hydroxynaphthalene17 5 required for the syn- thesis of the linear naphthopyrans 7b and 8 was obtained as delineated below (Scheme 2).The hydroxy ketone 5 on condensation with acetone a€orded 2,2-dimethyl-4H- naphtho[2,3-b]pyran-4-one 6 in 52% yield. The g-pyrone 6 was then converted into the 2,2-dimethylnaphtho[2,3-b]- pyran 8 and its dihydro derivative 7b by adopting the above conditions. To conclude, a convenient method has been described for the synthesis of naturally occurring angular naphthopyrans (4a and 4b), their dihydro derivatives (3a and 3b) and the new isomeric linear naphthopyrans (7b and 8).Experimental All melting points are uncorrected. 1H NMR spectra were recorded on a JEOL FX 90 Q instrument in CDCl3 using TMS as an internal standard, IR spectra on a Perkin-Elmer FT IR 1600 spectrophotometer. 2-Acetyl-3-hydroxynaphthalene 5.DA solution of the dimethyl- amide (0.022 mol), obtained from 2-methoxy-3-naphthoyl chloride (0.027 mol) and dimethylamine (40% aqueous solution, 70 ml), in dry benzene (50 ml) was treated with methylmagnesium iodide, prepared from methyl iodide (0.05 mol) and magnesium turnings (0.05 mol) with stirring.The reaction mixture was stirred for 4 h, then acidiRed using 1:1 HCl. The solvent layer, after work-up, provided the 2-acetyl-2-methoxynaphthalene as a dark oil. This (0.02 mol) was subjected to demethylation by treating it with an J. Chem. Research (S), 1998, 318�}319$ Scheme 1 Reagents and conditions: i, acetone, pyrrolidine, C6H6; ii, Zn�}Hg/HCl; iii, NaBH4, MeOH; iv, H3Oa, 658C Scheme 2 Reagents and conditions: i, MeMgI, C6H6; ii, AlCl3, CH2Cl2; iii, acetone, pyrrolidine, C6H6; iv, NH2NH2 H2O, ethylene glycol, KOH; v, NaBH4, MeOH; vi, H3Oa, 658C $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 318 J. CHEM. RESEARCH (S), 1998intimate mixture of anhydrous aluminium chloride (0.068 mol) anddry dichloromethane (50 ml), with vigorous stirring.The reactionmixture was stirred for 1 h. The excess of dichloromethane wasremoved under reduced pressure and the solid residue thus obtainedadded portionwise to ice-cold 1:1 HCl (70 ml), when a dark solidformed. This was ltered o, dried and puried by column chroma-tography over silica gel using hexane as the eluent. The 2-acetyl-3-hydroxynaphthalene was obtained as golden yellow akes (70%yield); mp 110 8C (lit.,17 110.0¡Ó111.8 8C) (Found: C, 77.38; H, 5.40.C12H10O2 requires C, 77.40; H, 5.4%); H 2.5 (3 H, s, CH3), 7.0(1 H, s, H-1), 7.1¡Ó7.9 (4 H, m, H-5, H-6, H-7, H-8), 8.0 (1 H, s,H-4), 12.6 (1 H, s, OH).2,2-Dimethylnaphthopyran-4-ones 2a, 2b and 6.A solution of theappropriate o-acetylnaphthol (0.0162 mol), pyrrolidine (0.0080 mol)and dry acetone (0.0240 mol) in dry benzene (30 ml) was rst stirredat room temperature for about 15 min.It was then reuxed using aDean Stark separator for about 48 h, then acidied with 1:1 HCl.The organic solvent layer which separated after work-up provided asemi-solid which on purication by column chromatography usingsilica gel and hexane aorded the desired -pyrone.Compound 2a. (Yield 60%); mp 124 8C (lit.,7 121 8C) (Found: C,74.96; H, 6.27. C16H16O3 requires C, 74.98; H, 6.29%); dH 1.49 [6 H,s, C(CH3)2], 2.67 (2 H, s, CH2), 3.82 (3 H, s, OCH3), 6.82 (1 H, s,H-5), 7.13¡Ó7.40 (2 H, m, H-8 and H-9), 7.76¡Ó8.00 (2 H, m, H-7 andH-10).Compound 2b.(Yield 65%); Oil (lit.,6 Oil) (Found: C, 79.60; H,6.23. C15H14O2 requires C, 79.62; H, 6.24%); dH 1.60 [6 H, s,C(CH3)2], 2.85 (2 H, s, CH2), 7.38 (1 H, d, J 9, H-5), 7.48¡Ó7.90(4 H, m, H-7, H-8, H-9, H-10), 8.33 (1 H, d, J 9, H-6 Hz).Compound 6. (Yield 52%); mp 96 8C (Found: C, 79.61; H, 6.22.C15H14O2 requires C, 79.62; H, 6.24%); dH 1.49 [6 H, s, C(CH3)2],2.84 (2 H, s, CH2), 7.25¡Ó7.45 (2 H, m, H-7 and H-10), 7.45¡Ó7.60(1 H, m, H-8), 7.73 (1 H, br, J 6, H-6), 7.90 (1 H, br, J 6 Hz, H-9),8.50 (1 H, s, H-5).3,4-Dihydro-2,2-dimethylnaphthopyrans 3a, 3b.Water (20 ml)was added to a mixture of zinc powder (2.00 g) and HgCl2 (0.10 g).The resulting slurry was shaken thoroughly for 5 min.To it wasadded HCl (50%, 10 ml) and the mixture again shaken vigorouslywhen zinc amalgam was obtained. To this zinc amalgam was addedthe -naphthopyrone (0.0022 mol) and HCl (80%, 25 ml) andthe contents were reuxed for 3 h.After completion of the reaction(Monitored by TLC) the contents were extracted with diethylether. Work-up of the organic layer provided a product whichon purication using column chromatography yielded the desireddihydronaphthopyrans.Compound 3a. (Yield 78%); mp 73 8C (lit.,14 76 8C) (Found: C,79.29; H, 7.47. C16H18O2 requires C, 79.31; H, 7.49%); dH 1.43 [6 H,s C(CH3)2], 1.90 (2 H, t, J 6, CH2CH2Ar), 2.90 (2 H, t, J 6,CH2CH2Ar), 3.95 (3 H, s, OCH3), 6.50 (1 H, s, H-5), 7.30¡Ó7.60(2 H, m, H-8 and H-9), 8.05¡Ó8.25 (2 H, m, H-7 and H-10).Compound 3b.(Yield 80%); Oil (lit.,12 Oil) (Found: C, 84.85; H,7.40. C15H16O requires C, 84.87; H, 7.60%); dH 1.48 [6 H, s,C(CH3)2], 1.95 (2 H, t, J 6, CH2CH2Ar), 2.93 (2 H, t, J 6,CH2CH2Ar), 7.20 (1 H, d, J 9, H-5), 7.28 (1 H, d, J 9, H-6), 7.35¡Ó7.50 (2 H, m, H-8 and H-9), 7.70¡Ó7.80 (1 H, m, H-7), 8.20¡Ó8.35(1 H, m, H-10).3,4-Dihydro-2,2-dimethylnaphtho[2,3-b] pyran 7b.A mixture of2,2-dimethyl-4H-naphtho[2,3-b]pyran-4H-one 6 (0.0022 mol), hydra-zine hydrate (0.5 ml) and ethylene glycol (10 ml) was reuxed for15 min.To this hot solution KOH pellets (0.0053 mol) were addedin portions over a period of 10 min, then reuxed for 1 h. Aftercooling, the reaction mixture was made acidic and extracted withether. Work-up of the orgvent layer provided a sticky masswhich was further puried by column chromatography yielding thedesired dihydronaphthopyran 7b (60% yield); mp 110 8C (Found:C, 84.86; H, 7.51.C15H16O requires C, 84.87; H, 7.60%); H 1.39[6 H, s, C(CH3)2], 1.92 (2 H, t, J 7, CH2CH2Ar), 3.01 (2 H, t, J 7,CH2CH2Ar), 7.17 (1 H, s, H-5), 7.22¡Ó7.36 (2 H, m, H-7 and H-8),7.55 (1 H, s, H-10) and 7.63¡Ó7.69 (2 H, m, H-6 and H-9).2,2-Dimethylnaphthopyrans 4a, 4b and 8.To a well stirredsolution of naphthopyran-4-one (0.0022 mol) in methyl alcohol(10 ml) was added NaBH4 (0.0026 mol) over a period of 20 min.Usual work-up provided a semi-solid residue which was dissolved inmethyl alcohol (10 ml), HCl (4 mol dm£¾3, 20 ml) added and heatedat 65 8C for about 30 min.The reaction mixture was cooled, pouredinto cold water and extracted with ether. Work-up of the etherlayer provided a semi-solid mass which on purication by columnchromatography yielded the desired product.Compound 4a. (Yield 71%); mp 56 8C (lit.,7 58 8C) (Found: C,79.96; H, 6.70. C16H16O2 requires C, 79.97; H, 6.71%); dH 1.55 [6 H,s, C(CH3)2], 3.97 (3 H, s, OCH3), 5.68 (1 H, d, J 11, H-3), 6.43(1 H, d, J 11 Hz, H-4), 6.55 (1 H, s, H-5), 7.43¡Ó7.65 (2 H, m, H-8and H-9), 8.10¡Ó8.35 (2 H, m, H-7 and H-10).Compound 4b.(Yield 73%); mp 42 8C (lit.,12 44 8C) (Found: C,85.66; H, 6.70. C15H14O requires C, 85.68; H, 6.71%); dH 1.48 [6 H,s, C(CH3)2], 5.58 (1 H, d, J 10, H-3), 6.42 (1 H, d, J 10, H-4), 7.11(1 H, d, J 9, H-5), 7.33 (1 H, d, J 9, Hz, H-6), 7.34¡Ó7.51 (2 H, m,H-8 and H-9), 7.58¡Ó7.82 (1 H, m, H-7), 8.06¡Ó8.31 (1 H, m, H-10).Compound 8.(Yield 62%); mp 91 8C (Found: C, 85.59; H, 6.69.C15H14O requires C, 85.68; H, 6.71%); dH 1.48 [6 H, s, C(CH3)2],5.82 (1 H, d, J 10, H-3), 6.51 (1 H, d, J 10 Hz, H-4), 7.14 (1 H, s,H-10), 7.20¡Ó7.40 (2 H, m, H-7 and H-8), 7.42 (1 H, s, H-5), 7.58¡Ó7.72 (2 H, m, H-6 and H-9).We thank Dr A. S. Inamdar, Principal, A.G. College,Pune for providing the necessary facilities, Professor R. S.Mali, University of Pune for useful discussions andUniversity of Pune for the spectral and elemental analyses.H. M.Godbole (SRF) and A. R. Joseph (JRF) thank CSIRfor providing the nancial assistance.Received, 3rd December 1997; Accepted, 9th February 1998Paper E/7/08718GReferences1 L. Hari, L. F. De Buyck and H. L. De Pooter, Phytochemistry,1991, 1726.2 A. R. Burnett and R. H. Thomson, J. Chem. Soc. C, 1968, 850.3 R. Livingstone and M. C. Whiting, J. Chem. Soc., 1955, 3631.4 A. R. Burnett and R. H. Thomson, J. Chem. Soc. C, 1968, 854.5 A. S. R. Anjaneyulu and Rao D. Satyanarayana, Indian J.Chem., Sect. B, 1997, 36, 424.6 A. S. R. Anjaneyulu, Row L. Ramachandra, Krishna C. Sri andC. Shrinivasulu, Curr. Sci., 1968, 37, 513.7 R. Livingstone and R. B. Watson, J. Chem. Soc., 1956, 3701.8 L. Elhadi, M. Laurence and Z. Henri, Synth. Commun., 1993,23, 3019.9 V. K. Tandon, M. Vaish, S. Jain, D. S. Bhakuni and R. C.Srimal, Indian J. Pharm. Sci., 1991, 53, 22.10 A. S. R. Anjaneyulu and B. Isaa, J. Chem. Soc., Perkin Trans.1, 1991, 2089.11 J. Hlubucek, E. Ritchie and W. C. Taylor, Tetrahedron Lett.,1969, 17, 1369.12 B. K. Rohatgi, R. S. Gupta and R. N. Khanna, Indian J.Chem., Sect. B, 1981, 20, 505.13 V. K. Ahluwalia, P. K. Hira and R. S. Jolly, Indian J. Chem.,Sect. B, 1982, 21, 961.14 A. K. Das Gupta, R. M. Chatterje and T. P. Bhowmic,Tetrahedron, 1969, 25, 4207.15 I. R. Green, J. Chem. Educ., 1982, 59, 698.16 H. J. Kabbe and A. Widdig, Angew. Chem., Int. Ed. Engl., 1982,21, 247.17 I. M. Hunsberger, J. Am. Chem. Soc., 1950, 72, 5626.J. CHEM. RESEARCH (S), 1998 319

ISSN:0308-2342    

DOI:10.1039/a708718g

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Influence of Ionic Strength and Cation Nature on the Deprotonation of Methanediol in Alkaline Solution$ Eugenijus Norkus,*a Rasa Pauliukaite¡ì ,a Algirdas Vas©« kelis,a Eugenijus Butkus,b Zenonas Jusysa and Marija Krenevic©« iene¡ìb aInstitute of Chemistry, A. Gos©« tauto 9, 2600 Vilnius, Lithuania bDepartment of Organic Chemistry, Vilnius University, Naugarduko 24, 2006 Vilnius, Lithuania The pKa values of methanediol deprotonation were found to decrease with increase in solution ionic strength as estimated by a 13C NMR titration method. Formaldehyde is hydrated in aqueous solutions forming methanediol: HCHO a H2O¢§¢§¢§4 3¢§¢§¢§H2COOHU2 O1U The equilibrium constant of reaction (1) was found to be 2103 1 and 2.3103.2,3 This suggests that nearly all for- maldehyde is present in hydrated form in aqueous solutions.In alkaline aqueous solutions dissociation (deprotonation) of methanediol occurs:4 H2COOHU2 Ka ¢§¢§¢§4 3¢§¢§¢§H2COOHUO¢§ a Ha O2U or H2COOHU2 a OH¢§ ¢§¢§¢§4 3¢§¢§¢§H2COOHUO¢§ a H2O O3U Methanediol and its anion are assumed to be of di€erent activity in various reactions, e.g.methanediol anion rather than methanediol is thought to participate in anodic oxi- dation of formaldehyde in alkaline solutions.5¡¾10 However, methanediol is an active species during the interaction with tartrate.11 Therefore it is important to know the exact value of the deprotonation constant (pKa) of methanediol. Di€erent values of methanediol deprotonation constants (pKa from 12.5 to 13.6 at 20¡¾25 8C) were obtained using various experimental techniques: 12.5 (spectrophotometry),12 13.1 (13C NMR),7 13.3 (conductometry)13 13.42 and 13.6 (polarography).14 The scatter in the available pKa values can be attributed to the di€erent ionic strengths of the solutions investigated.Therefore the aim of this work was to determine the in.uence of ionic strength on methanediol deprotonation. The systems investigated were: CH2O¡¾ KOD¡¾KNO3¡¾D2O, CH2O¡¾NaOD¡¾NaNO3¡¾D2O and CH2O¡¾LiOD¡¾LiNO3¡¾D2O.Results and Discussion To study the equilibrium between methanediol and its anion form we have used 13C NMR spectroscopy. Various NMR techniques can be used, e.g. 1H, however the latter method is not very accurate since the di€erence of the chemical shift between two forms in some solutions does not exceed 0.1 ppm.15 The 13C spectra were measured in formaldehyde solutions (0.38 mol dm¢§3) at the ionic strength (I) of the electro- lyte, 0.4 and 1.0 mol dm¢§3.Formaldehyde solutions in water are known to form polyoxymethylene glycols of various compositions and molecular weights.4 In this work we studied alkaline solutions of formaldehyde prepared by dissolving trioxymethylene in supporting electrolyte solutions. The low concentration of formaldehyde was used to avoid oligomer formation and no signals of the oligo- meric forms of formaldehyde were observed in the NMR spectra under these conditions.Owing to the rapid proton exchange between methanediol and its anion a single 13C signal which is the weighted average of the shift of both species is observed in the spectrum. The chemical shift (d) of the protonated form of methanediol is observed at 83.0 ppm in accordance with literature data.16 The chemical shift was measured relative to the methylene and methyl carbon lines of ethanol as a reference compound by addition of ca. 10% J. Chem. Research (S), 1998, 320¡¾321$ Fig. 1 The 13C chemical shift of methanediol vs. pD at 25 8C [CH2O] a 0.38 mol dm¢§3 I/mol dm¢§3 a 0.4 (a), 1.0 (b). w, LiOD a LiNO3; *, NaOD a NaNO3; &, KODa KNO3 $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 (e-mail: Norkus@ktl.mii.lt). 320 J. CHEM. RESEARCH (S), 1998ethanol to the electrolyte solution.To obtain a reliable 13Csignal in the strongly alkaline solutions, i.e. pHr13.5, agreater number of scans was necessary due to the longerrelaxation times of the methanediol anion caused by astronger solvation of the nuclei and the increased viscosityof the solution. However, the chemical shift values were notchanged within the measurement error on varying the pulseinterval. A shift of the methylene carbon of methanediol tolower elds was observed in all cases with increasing pH ofthe alkaline solutions.Although the methanediol anionis more strongly solvated in such solutions the deshieldingeect of the charged oxygen atom is dominant. TheCannizzaro reaction did not proceed signicantly during theperiod of recording spectra as the probes were analysed bypolarography.17The dependences of the 13C chemical shift of methanediolvs. pD (Fig. 1) have a form18,19 typical of titration curvesfrom which pKa values were determined.We suppose thatthe conversion of the protonated and the base form ofmethanediol in eqn. (2) corresponds to a linear scale vs. thechemical shift value at least in the range of pH below 13.5,as has analogously been found for carboxylic acids andother small molecules.20 Thus the pKa values were taken asthe inection point of the dependence of d vs. pD.The results obtained show a trend of decrease in pKavalues with increase in ionic strength of the solution(Table 1). The pKa values of methanediol deprotonationwere found to be in the range from 13.05 to 13.55 inCH2O¡ÓD2O solution depending on the ionic strength andthe cation of the supporting electrolyte.This decreasein pKa values is consistent with the known trend of theinuence of ionic strength on the reaction rate constant, i.e.the ionic strength does not inuence the rate constant ofreaction between non-charged species [direct reaction (2)]and increases the rate of reaction involving two species withopposite charge [reverse reaction (2)].21,22When comparing numerical pKa values at the ionicstrengths 0.4 and 1.0 mol dm£¾3 respectively it is seen thatthe smallest dierence is observed in the case of LiOD¡ÓLiNO3 as supporting electrolyte and the dierence rises inthe sequence of alkali-metal ions Li<Na<K. This canbe related to dierent changes in the activity coecients ofLiNO3, NaNO3 and KNO3 with increase in concentration,e.g.with increase in molal concentration from 0.5 to 1.0 molkg£¾1 in the case of LiNO3 the activity coecient changesinsignicantly (rises 0.018), and considerably decreases inNaNO3 solution (0.070) and, especially, in KNO3 solution(0.103).23ExperimentalThe 13C NMR spectra were recorded on a Tesla BS 587Aspectrometer operating at 20 MHz with intervals of 2, 5 and 10 sbetween the pulses, the probe temperature being 2521 8C.D2Owith deuterium content 99.8% was used as a solvent and ethanol asinternal standard. The chemical shifts were measured relative to themethylene and methyl carbon lines of ethanol with an accuracy of0.1 ppm.The solutions for spectral measurements were prepared bydissolving known amounts of paraformaldehyde (trioxymethylene)in solutions containing deuteriated alkali-metal hydroxides andnitrates and were allowed to equilibrate for several minutes beforerecording the spectra. The ionic strength of solutions was kept con-stant at 0.4 or 1.0 mol dm£¾3.The pD of solutions was measured using an EV-74 pH-meter(Belarus). The glass electrode was kept in 0.1 mol dm£¾3 DClsolution before the measurements.The calibration was carriedout by taking into account known values of the NaOD activitycoecients in D2O and the ionic product of D2O, equal to 14.96.2Received, 29th September 1997; Accepted, 9th February 1998Paper E/7/06993FReferences1 P. Greenzaid, Z. Luz and D. Samuel, J. Am. Chem. Soc., 1967,89, 749.2 A. Calusaru, L. Crisan and J. Kuta, J. Electroanal. Chem.Interfacial Electrochem., 1973, 46, 51.3 P.Valenta, Collect. Czech. Chem. Commun., 1960, 25, 853.4 J. F. Walker, Formaldehyde, Reinhold Publ. Corp., New York,1964.5 R. S. Buck and L. R. Grith, J. Electrochem. Soc., 1962, 109,1005.6 J. E. A. M. van den Meerakker, J. Appl. Electrochem., 1981, 11,395.7 R. Schumacher, J. J. Pesek and O. R. Melroy, J. Phys. Chem.,1985, 89, 4338.8 Z. Jusys, J. Electroanal. Chem. Interfacial Electrochem., 1994,375, 257.9 Z. Jusys and A. Vas kelis, Electrochim. Acta, 1997, 42, 449.10 A.Vas kelis, E. Norkus, R. Jus kenas, E. Matulionis andG. Stalnionis, Galvanotechnik, 1995, 86, 2114.11 E. Norkus, A. Vas kelis, E. Butkus and Pauliukaite , J. Chem.Res., 1997, (S) 126, (M) 0842.12 D. Barnes and P. Zuman, J. Electroanal. Chem., InterfacialElectrochem., 1973, 46, 323.13 R. P. Bell and D. P. Onwood, Trans. Faraday Soc., 1962, 58,1557.14 K. Vesely and R. Brdicka, Collect. Czech. Chem. Commun.,1947, 12, 313.15 M. Hellin, J. Delmau and F. Coussemant, Bull. Soc. Chim. Fr.,1967, 3355.16 I. Ya. Slonim, A. G. Gruznov, T. F. Oreshnikova, V. N.Klyuchnikov, L. M. Romanov and R. Z. Pavlikov, Vysokomol.Soed., 1987, 29, 282.17 E. Norkus, Pauliukaite and A. Vas kelis, Ber. Bunsenges. Phys.Chem., submitted.18 G. de Vit, A. P. G. Kiebom and H. van Bekkum, TetrahedronLett., 1975, 3943.19 D. L. Holmes and D. A. Lightner, Tetrahedron, 1995, 51, 1607.20 D. Farcasiu and A. Ghenciu, Prog. Nucl. Magn. Reson.Spectrosc., 1996, 29, 129.21 P. C. Jordan, Chemical Kinetics and Transport, Plenum Press,New York, 1980.22 K. A. Connors, Chemical Kinetics. The Study of Reaction Ratesin Solution, VCH, New York, 1990.23 D. Dobos, Electrochemical Data, Akademiai Kiado, Budapest,1978.Table 1 Dependence of methanediol pKa values(calculated from 13C NMR data) on the ionicstrength of solution at 25 8CI/mol dm£¾3 Supporting electrolyte pKa0.4 LiOD¡ÓLiNO3 13.55NaOD¡ÓNaNO3 13.25KOD¡ÓKNO3 13.551.0 LiOD¡ÓLiNO3 13.45NaOD¡ÓNaNO3 13.05KOD¡ÓKNO3 13.30J. CHEM. RESEARCH (S), 1998 321

ISSN:0308-2342    

DOI:10.1039/a706993f

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Simple Reduction of Various Ketones with Sodium Tetrahydroborate and Alumina in Hexane$ Shigetaka Yakabe,a Masao Hirano,*a James H. Clarkb and Takashi Morimotoa aDepartment of Applied Chemistry, Faculty of Technology, Tokyo University of Agriculture and Technology (TUAT), Koganei, Tokyo 184-8588, Japan bDepartment of Chemistry, University of York, Heslington, York YO1 5DD, UK A combination of NaBH4 and alumina preloaded with a small amount of water is a highly efficient reducing agent for cycloalkanones, substituted cyclohexanones and unsaturated and aromatic ketones in hexane, affording the corresponding alcohols in excellent yields under mild conditions (20�}60 8C).There are many reagents and methodologies available for the catalytic and stoichiometric reduction of a broad range of functional groups.1 Sodium tetrahydroborate (NaBH4) is one of the most extensively employed hydride donors,2 owing to its mild reducing capability and versatility. In addition, its insensitivity to moisture and relatively easy exchangeability of the Naa ion for other cations (Lia, Ca2a, Ba2a, Zn2a, Al3 a, Sn4a)2 to produce agents with di€erent reducing power, chemo- and/or stereo-selectivities make NaBH4 very attractive as a major laboratory synthetic reagent.2,3 Recently, we have observed that in situ generated alumina-supported reagents can be successfully used for the selective oxidation of sulRdes,4a�}c alcohols,4d,e and ketones4f and the regioselective nuclear monochlorination of activated arenes4g,h in water-free media.The remarkable ability of alumina to catalyse the reactions under mild conditions led us to investigate the reduction of organic compounds with a combination of NaBH4 and alumina. Although alumina-supported NaBH4 reagents are known to e€ect reductions5,6 and some of these are now available from commercial sources (Aldrich, Fluka, etc.), their prep- aration is time-consuming (i.e. a few hours' thorough mixing of alumina and aqueous NaBH4, followed by overnight drying in vacuo)5b and commercial reagents are rather ex- pensive.Consequently, it is of value to provide a convenient reduction method based on the use of NaBH4 under solid- solution biphasic conditions by taking advantages of our in situ method.4,7 The reduction of a ketone 1 was carried out instantly by eciently stirring a heterogeneous mixture of NaBH4, 1, and hexane under a dry atmosphere in the presence of chro- matographic neutral alumina preloaded with the optimum amount of water (moist alumina; vide infra).The reaction was clean and did not su€er from the formation of any by-product, and therefore essentially pure alcohol 2 was obtained simply by Rltration of the insoluble materials and removal of the solvent from the combined Rltrate and wash- ings. The applicability of the NaBH4/moist alumina system for typical ketones is summarised in Scheme 1 and Table 1. Thus, simple C5�}C12 alicyclic ketones 1a�}e (Entries 1�}5), substituted cyclohexanones 1f�}j (Entries 6�}10), and aro- matic ketones 1m and 1n (Entries 13 and 14, respectively) were readily reduced to a€ord the corresponding alcohols in excellent to quantitative yields under optimum conditions.Successful reduction of the steroidal ketone 1k (Entry 11) and the unsaturated ketone 1l (Entry 12) might extend the utility of the current procedure. Independent reactions of cyclohexanone 1b, 2-methylcyclohexanone 1f, and 2-tert- butylcyclohexanone 1i under the conditions of Entry 2 showed that their conversions were 100, 78, and 44%, respectively, clearly indicating that their apparent reactivities towards NaBH4 decrease as the substituents adjacent to the J.Chem. Research (S), 1998, 322�}323$ Scheme 1 Table 1 Reduction of ketones to the alcohols with NaBH4 and moist alumina in hexanea Entry Ketone NaBH4 (mmol) T/8C t/h moist Al2O3/g Alcohol (%)b 1 1a 0.3 20 1 0.5 2a (97) 2 1b 0.3 20 1 0.5 2b (92) 3 1c 0.3 20 3 0.5 2c (quant.) 4 1d 0.5 30 3 1.0 2d (quant.) 5 1e 0.6 60 3 0.5 2e (98) 6 1f 0.4 30 3 1.0 2f (87) 7 1g 0.3 20 1 0.5 2g (93) 8 1h 0.3 20 1 0.5 2h (91) 9 1i 0.8 40 3 1.5 2i (quant.) 10 1j 0.5 30 3 1.0 2j (quant.) 11 1k 0.3 40 3 0.5 2k (96) 12 1l 0.3 40 3 0.5 2l (quant.) 13 1m 0.3 40 3 0.5 2m (98) 14 1n 0.4 60 3 0.5 2n (98) 15c 1n 16 60 3 10 2n (quant.) aKetone 1 mmol, hexane 10 ml.bIsolated yield of 2 based on the starting 1. cBenzophenone 1n: 40 mmol (7.28 g), hexane 50 ml, and ether washing (530 ml) were used.$This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 322 J. CHEM. RESEARCH (S), 1998carbonyls (R1 in Scheme 1) increase in size. This fact might suggest that the steric hindrance of the alkyl groups plays an important role in determining the reactivities of the ketones.The current procedure can favorably be compared to the reduction with the preformed alumina-supported NaBH4 reagent.5b Indeed, the reduction of benzophenone 1n gave benzhydrol 2n in superior yield (98%) to that obtained by the earlier procedure, in which crude 2n was obtained in 88% yield.5b Finally, an attempted reduction of 1n on a large (40 mmol) scale was accomplished successfully (Entry 15). In conclusion, the in situ generated alumina-supported NaBH4 reagent serves as a convenient, inexpensive and high-yielding reduction system for various ketones under mild conditions.Experimental General.DThe 1H NMR spectra were recorded on a JEOL PMX- 60 (60 MHz) spectrometer for solutions using deuteriochloroform with TMS as an internal standard. Analytical gas chromatography was performed on a Shimadzu GC-14B instrument with a 2 m4 mm diameter column packed with 5% PEG-20M on Chromosorb WAW-DMCS, with temperature programming.Mass spectra were determined on a JEOL SX-102A mass spectrometer coupled to a Hewlett-Packard GC5890 Series II GC apparatus via a heated capillary column. Starting Materials.DHexane was rigorously dried (CaCl2), dis- tilled and stored over molecular sieves. Commerical NaBH4 was ground to a Rne powder in a dry-box and stored in a desiccator. Ketones 1a�}n were available from commercial sources and used without further puriRcation. Moist alumina (water content 10 wt%) was prepared by adding deionised water (0.05 g) to predried (500 8C, 6 h) alumina (ICN BIOMEDICALS, Alumina N, Super I; 0.45 g) in portions, followed by vigorous shaking of the mixture on every addition for a few minutes until a free-�Powing powder was obtained, which was immediately used for the reduction.Typical Reduction Procedure.DA heterogeneous mixture of benzophenone 1n (1 mmol; 0.182 g), hexane (10 ml), Rnely ground NaBH4 (0.4 mmol; 0.151 g) and freshly prepared moist alumina (0.5 g) in a 30 ml round-bottom �Pask was vigorously stirred for 3 h at 60 8C.The cooled reaction mixture was transferred onto a sintered glass funnel, and the Rlter cake thoroughly washed with portions of dry diethyl ether (ca. 60 ml). Removal of the solvent from combined clear Rltrate on a rotary evaporator gave satisfac- torily pure (GC, NMR, and TLC) benzhydrol 2n in 98% yield (0.180 g): mp 63.2�}63.8 8C (lit.,8 mp 65�}67 8C). The reductions of ketones 1a�}m with the NaBH4/moist alumina system were performed under conditions determined in terms of their reactivity and the yield of 2, followed by the normal work-up, a€orded alcohols 2a�}m, which were fully characterised by spectro- scopic comparisons (IR, NMR, and MS) with commercial authentic samples.It is noteworthy that although certain ketones and alcohols have only limited solubilities in hexane under the conditions employed, the reduction of the ketones and work-ups of the products were readily achieved.A large-scale reduction of 1n was carried out under the conditions indicated in Entry 15 to a€ord 2n quantitatively. The authors wish to thank Dr Masahiro Natsume for the provision of GC�}MS facilities at TUAT. One of us (J.H.C.) would like to thank the RAEng/EPSRC for a Clean Technology Fellowship. Received, 18th December 1997; Accepted, 9th February 1998 Paper E/7/09081A References 1 (a) H. O. Ho W.A. Benjamin, California, 1972, ch. 1�}4, (b) J. March, Advanced Organic Chemistry. Reactions, Mechanisms, and Structure, Wiley, New York, 1992, 4th edn., ch. 19; (c) M B. Smith, Organic Synthesis, McGraw-Hill, New York, 1992, ch. 4; (d) J. S. Pizey, Synthetic Reagents, Ellis Horwood, Chichester, 1974, vol. 1, ch. 2; (e) C. F. Lane, Synthesis, 1975, 135; ( f ) J. M. Khurana and A. Gogia, Org. Prep. Proced. Int., 1997, 29, 3. 2 For example, see ref. 1(c), section 4.5.B. 3 See Ref 1(a), ch. 2; ref. 1(b), ch. 19, pp. 1206�}1223. 4 (a) M. Hirano, S. Yakabe, S. Itoh, J. H. Clark and T. Morimoto, Synthesis, 1997, 1161; (b) M. Hirano, S. Yakabe, J. H. Clark and T. Morimoto, J. Chem. Soc., Perkin Trans. 1, 1996, 2693; (c) M. Hirano, S. Yakabe, J. H. Clark, H. Kudo and T. Morimoto, Synth. Commun., 1996, 26, 1875; (d ) M. Hirano, S. Nagasawa and T. Morimoto, Bull. Chem. Soc. Jpn., 1991, 64, 2857; (e) M. Hirano, H. Kuroda and T. Morimoto, Bull. Chem. Soc. Jpn., 1990, 63, 2433; ( f ) M.Hirano, M. Oose and T. Morimoto, Chem. Lett., 1991, 331; (g) M. Hirano, S. Yakabe, H. Monobe, J. H. Clark and T. Morimoto, J. Chem. Soc., Perkin Trans. 1, 1997, 3081; (h) M. Hirano, S. Yakabe, H. Monobe, J. H. Clark and T. Morimoto, Synth. Commun., 1997, 27, 3749. 5 (a) F. Hodosan and N. Serban, Rev. Roum. Chim., 1969, 14, 121; (b) E. Santaniello, F. Ponti and A. Manzocchi, Synthesis, 1978, 891; (c) E. Santaniello, C. Farachi and A. Manzocchi, Synthesis, 1979, 912. 6 See E. Santaniello, Preparative Chemistry using Supported Reagents, ed. P. Laszlo, Academic Press, San Diego, 1987, ch. 18, p. 181 and 182; J. M. Maud, Solid Supports and Catalysis in Organic Synthesis, ed. K. Smith, Ellis Horwood, Chichester, 1992, p. 356 and 357. 7 J. H. Clark, Catalysis of Organic Reactions by Supported Inorganic Reagents, VCH, New York, 1994; J. H. Clark, A. P. Kybett and D. J. Macquarrie, Supported Reagents. Preparation, Analysis, and Applications, VCH, New York, 1992; Preparative Chemistry Using Supported Reagents, ed. P. Laszlo, Academic Press, San Diego, 1987; Solid Supports and Catalysis in Organic Synthesis, ed. K. Smith, Ellis Horwood, Chichester, 1992; M. Balogh and P. Laszlo, Organic Chemistry Using Clays, Springer, Berlin, 1993. 8 Dictionary of Organic Compounds, Chapman and Hall, London, 6th edn., 1996. J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a709081a

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Solid State Oxidation of Benzoins on Alumina-Supported Copper(II) Sulfate under Microwave Irradiation$ Rajender S. Varma,* Dalip Kumar and Rajender Dahiya Department of Chemistry and Texas Regional Institute for Environmental Studies (TRIES), Sam Houston State University, Huntsville, TX 77341-2117, USA Benzoins are rapidly oxidised to benzils in high yields by the solid reagent system copper(II) sulfate�}alumina, under the influence of microwaves. The oxidative transformation of benzoins to benzils has been accomplished by a variety of reagents namely nitric acid,1 Fehling's solution,1 thallium(III) nitrate (TTN),2,3 ytterbium(III) nitrate,4 clayfen5 and ammonium chlorochromate�}alumina.6 Besides extended reaction times, most of these processes su€er from drawbacks such as the use of corrosive acids and toxic metallic compounds that generate undesirable waste materials.Consequently, there is a need for the development of a manipulatively easy and environmentally benign solvent-free protocol for the oxidation of benzoins.In this context, organic reactions on solid supports7,8 and those assisted by microwaves,8�}10 especially under solvent-free conditions,8,9 have attracted attention recently because of their enhanced selectivity, milder reaction conditions and associated ease of manipu- lation. Since only the polar reactants adsorbed on the surface of the solid support absorb microwaves, a variety of reagents supported on such surfaces can be utilised for the enhancement of organic reactions using an unmodiRed microwave oven.We have an ongoing program to develop solvent-free synthetic protocols that are accelerated by ultrasound or microwave irradiation.8 A recent report on the utility of copper salts for the oxidation of hydroquinones and coupling of naphthols11 prompts us to report our results on the facile oxidation of benzoins to benzils that proceeds expeditiously using copper(II) sulfate impregnated on alumina. A wide variety of benzoins, symmetrical as well as unsymmetrical (Table 1), undergo rapid oxidation with this solid reagent system, CuSO4�}Al2O3, to a€ord vicinal diketones in high yields within 2�}3 min of microwave irradiation. These solvent-free reactions are conducted by mixing benzoins thoroughly with the catalyst followed by irradiation in a domestic microwave oven.The optimum ratio of substrate to reagent is found to be (1:0.85, mole:mole) that ensures complete conversion of benzoins into benzils.Interestingly, the oxidative protocol is e€ective only for a-hydroxyketones; other secondary alcohols, includ- ing 1,2-diphenylethane-1,2-diol, are not oxidised under these conditions. Experimental Melting points are uncorrected. A Sears Kenmore household microwave oven operating at 2450 MHz was used at its full power of 900 W for all the experiments. The products were identiRed by comparison of the mp, IR and NMR spectra of the products with authentic samples.Preparation of the Reagent, CuSO4�}Al2O3.DNeutral alumina (25 g) was added to a well stirred solution of copper sulfate penta- hydrate (3.9 g) in distilled water (50 ml) vacuum. The resulting sky blue powder was stored in a tightly closed bottle and used without prior activation. The reagent retains its activity for an extended period; the original batch is still active 3 years after its preparation. General Oxidation Procedure.DBenzoin (1 mmol) and CuSO4�} Al2O3 (1.5 g, 0.85 mmol of CuSO4 5H2O) were mixed thoroughly on a vortex mixer.The reaction mixture contained in glass tubes was placed in an alumina bath (heat sink) inside the microwave oven and irradiated for a speciRed time. On completion of the reaction, followed by TLC examination (hexane-ethyl acetate, 9:1), the product was extracted into methylene chloride (310 ml). The solvent was removed under reduced pressure and the residue crystal- lised from an appropriate solvent to a€ord nearly quantitative yields of benzils.That the e€ect may not be purely thermal12 is borne out by the fact that for a similar product yield the reaction could be completed in 1.5 h (entry 1, Table 1) at the same bulk temperature of 120 8C using an alternate mode of heating (oil-bath); the temperature of the reaction mixture inside the alumina bath reached0120 8C after J. Chem. Research (S), 1998, 324�}325$ Table 1 Oxidation of benzoins on CuSO4�}Al2O3 under microwave irradiation mp ( 8C) Entry R1 R2 t/min Yield(%)a found reported 1 Ph Ph 2.0 96 92�}93 94�}963 2 Ph p-MeC6H4 3.0 81 30�}31 29�}305 3 Ph p-MeOC6H4 2.5 85 62 62�}635 4 p-ClC6H4 p-ClC6H4 3.5 82 194�}196 195�}1973 5 p-MeC6H4 p-MeC6H4 2.0 92 102�}104 101�}1043 6 p-MeOC6H4 p-MeOC6H4 2.5 86 131�}133 132�}1343 7 2.5 82 161�}163 162�}1646 aRefers to pure isolated products obtained. 2 min of irradiation in a microwave oven operating at full power of 900 W. In conclusion, this solvent-free oxidation of benzoins using CuSO4-`doped' alumina is a simple and high-yielding protocol $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence (e-mail: chm_rsv@shsu.edu). 324 J. CHEM. RESEARCH (S), 1998which avoids the drastic conditions that are typical of conventional oxidation reactions. Yet another environmentally benign feature is that the alumina support employed can be recovered and reused after washing o€ the products; the usual activation of the support by heating at elevated temperatures under vacuum for extended periods is not required.We are grateful to the Texas Advanced Research Program (ARP) in chemistry (Grant No. 003606-023) and Texas Regional Institute for Environmental Studies (TRIES) for Rnancial support. Received, 22nd December 1997; Accepted, 9th February 1998 Paper E/7/09148F References 1 J.S. Buck and S. S. Jenkins, J. Am. Chem. Soc., 1929, 51, 2163 and refs. therein. 2 A. McKillop, B. P. Swann and E. C. Taylor, Tetrahedron Lett., 1970, 5281. 3 A. McKillop, B. P. Swann, M. E. Ford and E. C. Taylor, J. Am. Chem. Soc., 1973, 95, 3641. 4 P. Girara and H. B. Kagan, Tetrahedron Lett., 1975, 4513. 5 M. Besemann, A. Cornelis and P. Laszlo, C. R. Acad. Sci. Ser. C, 1984, 299, 427. 6 G.-S. Zhang, Q.-Z. Shi, M.-F.Chen and K. Cai, Synth. Commun., 1997, 27, 9534. 7 A. McKillop and D. W. Young, Synthesis, 1979, 401, 481; P. Laszlo, Preparative Chemistry using Supported Reagents, Academic Press, San Diego, 1987; K. Smith, Solid Supports and Catalyst in Organic Synthesis, Ellis Horwood, Chichester, 1992; J. H. Clark, Catalysis of Organic Reactions by Supported Inorganic Reagents, VCH, New York, 1994. 8 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, Tetrahedron Lett., 1997, 38, 6525; R. S. Varma, R. Dahiya and R. K. Saini, Tetrahedron Lett., 1997, 38, 7029, 7823; R. S. Varma and R. K. Saini, Tetrahedron Lett., 1997, 38, 4337; 1998, 39, 1481. 9 D. Villemin and A. Benalloum, Synth. Commun., 1991, 21, 1, 63; A. Oussaid, L. N. Thach and A. Loupy, Tetrahedron Lett., 1997, 38, 2451; J. M. Lerestif, L. Toupet, S. Sinbandhit, F. Tonnard, J. P. Bazureau and J. Hamelin, Tetrahedron, 1997, 53, 6351. 10 A. G. Whittaker and D. M. P. Mingos, J. Microwave Power Electromagn. Energy, 1994, 29, 195; S. Caddick, Tetrahedron, 1995, 51, 10403; C. R. Strauss and R. W. Trainor, Aust. J. Chem., 1995, 48, 1665; A. K. Bose, B. K. Banik, N. Lavlinskaia, M. Jayaraman and M. S. Manhas, Chemtech, 1997, 27, 18; R. S. Varma, in Microwaves: Theo, ed. D. Clark, W. Sutton and D. Lewis, American Ceramic Society, Ceramic Transactions, 1997, vol. 80, pp. 357�} 365. 11 T. Sakamoto, H. Yonehara and C. Pac, J. Org. Chem., 1997, 62, 3194. 12 D. Raner, C. R. Strauss, F. Vyskoc and L. Mokbel, J. Org. Chem., 1993, 58, 950. J. CHEM. RESEARCH (S), 1998 3

ISSN:0308-2342    

DOI:10.1039/a709148f

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Synthesis and Diels¡¾Alder Reaction of Acetylenic Sulfonate$ Albert W. M. Lee,* W. H. Chan, Z. P. Zhong, K. F. Lee and Anissa B. W. Yeung Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong The first synthesis of acetylenic sulfonate and its Diels¡¾Alder reactions are reported. Diels¡¾Alder reactions are amongst the most useful and versatile reactions in organic synthesis. In a single trans- formation, two new carbon¡¾carbon bonds and a six- membered ring system are formed.Much e€ort has been devoted to the design of new and e.cient dienophiles1 for the Diels¡¾Alder process including the acetylenic sulfoxides reported by us.2.3 It has long been our interest to explore the use of sulfur base functionality to activate vinylic4 or acetylenic5 units to serve as two-carbon synthons in organic synthesis, in particular the syntheses of heterocycles and alkaloids. Sulfoxide, sul¢çnate6 and recently sultone7 have been used by us as the activators.We envisioned that sulfonate which is a powerful electron-withdrawing group8 should be another ideal activator of an acetylenic dieno- phile. Sulfonate is a very common functional group in organic synthesis, mainly used as a leaving group through cleavage of C0O bonds. However, it is seldom used as an activator through C0S linkages. One exception may be the vinylene sulfonates which have been successfully used as dienophiles in both inter-9 and intra-molecular10 Diels¡¾Alder reactions.To follow our previous report on the synthesis and Diels¡¾ Alder reactions of acetylenic sul¢çnates,6 we report the ¢çrst synthesis of the previously unknown acetylenic sulfonate and its reactions in Diels¡¾Alder processes. Our approach to the synthesis of the acetylenic sulfonate is through oxidation of the corresponding sul¢çnate ¢çrst prepared by us based on the chemistry described by Whitesell11 in a two-step one-pot reaction. Cyclohexanol was treated with a ten-fold excess of thionyl chloride in diethyl ether at ¢§20 8C.After the reaction, the excess of thionyl chloride was removed at low temperature under high vacuum. The remaining labile cyclohexanosul¢çnyl chloride was then treated with 2-triisopropyl- or 2-trimethyl- silylethynyllithium to a€ord acetylenic sul¢çnate 1 or 2 respectively in good yield. Compound 1 is more stable than 2 which sometimes decomposes upon storage. Although oxidation of sul¢çnate to sulfonate may look straightforward, only a few isolated examples have been reported using potassium permanganate,12a hydrogen peroxide12b and peracid12c as the oxidizing agents.To our surprise, the triisopropylsilyl-protected acetylenic sul¢çnate resisted oxidation by many oxidants we tried including MCPBA, OXONE, H2O2¡¾SeO2 and RuO4 generated from RuCl3¡¾NaIO4.13 Eventually, 1 or 2 was ¢çrst deprotected to acetylenic sul¢çnate 3 (84% overall yield from cyclohexanol) which could then be smoothly oxidized by MCPBA at room temperature to the previously unknown acetylenic sulfonate, cyclohexyl ethynesulfonate 4, in 83% isolated yield (Scheme 1).Cyclohexyl ethynesulfonate 4 is a colour- less viscous liquid which has to be stored at 0 8C to avoid decomposition. The results of the Diels¡¾Alder reactions of 4 with a series of dienes are summarized in Table 1. For reactive dienes such as cyclopentadiene the cycloaddition took place readily at 0 8C to a€ord the bicyclic cycloadduct 6 in almost quantitative yield.Incidentally, compound 6 has also been synthesized by us through the oxidation of the cycloadduct 5 of acetylenic sul¢çnate 3 with cyclopentadiene.6 As depicted in Scheme 2, acetylenic sul¢çnate and acetylenic sulfonate are complementary dienophiles in the Diels¡¾Alder process. To prepare compound 6, oxidation could take place either at the dienophile (3 to 4) or at the cycloadduct (5 to 6). For less reactive dienes, the reactions were carried out at elev- ated temperatures or under sealed-tube conditions if the dienes were volatile.For unsymmetrical dienes 1:1 mixtures of regeoisomers resulted. We also found that the addition of a tiny amount of BHA or BHT to the reaction mixtures generally improved the yields and suppressed the formation of polymeric side products. In summary, we report the ¢çrst synthesis of the acetylenic sulfonate and its Diels¡¾Alder reactions. Further studies including Michael addition of nucleophiles to the vinylic sulfonate cycloadducts are in progress.Experimental The NMR spectra were recorded on a JEOL-EX 270 (270 MHz for 1H and 67.8 MHz for 13C) spectrometer in CDCl3 with tetra- methylsilane as internal standard, infrared spectra on a Hitachi J. Chem. Research (S), 1998, 326¡¾327$ Scheme 1 Reagents: (i) excess of SOCl2/Et2O, ¢§20 8C; (ii) RC2CLi; (iii) KF/MeCN; (iv) MCPBA Scheme 2 $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 326 J. CHEM. RESEARCH (S), 1998270-30 spectrometer and mass spectral data on an EI MS30spectrometer.Cyclohexyl Ethynelsulfonate 4.Cyclohexyl ethynesulnate pre-pared according to ref. 6 (0.56 g, 3.26 mmol) was stirred withm-chloroperoxybenzoic acid (MCPBA) (1.12 g, 6.52 mmol) inmethylene chloride (12 ml) for 48 h at room temperature.Themixture was then quenched with 10% aqueous sodium hydroxidesolution (2.6 ml). The mixture was extracted with methylene chlor-ide (310 ml). The combined extracts were dried over anhydroussodium sulfate followed by concentration. The crude product waspuried by column chromatography on silica gel using 5% ethylacetate in light petroleum as eluent to give sulfonate 4 as a colour-less oil (0.51 g, 83%): H (270 MHz, CDCl3) 1.31¡Ó2.04 (10 H, m),3.31 (1 H, s), 4.80¡Ó4.88 (1 H, m); C (67.8 MHz, CDCl3) 23.18,24.66, 31.95, 76.03, 77.83 and 86.04; IR 2080 cm£¾1 (Found: M,m/z 188.0510.C8H12O3S requires 188.0508).Diels¡ÓAlder Reaction of Cyclopentadiene with Sulfonate 4.At0 8C and under a nitrogen atmosphere, cyclohexyl ethynesulfonate(50.4 mg, 0.27 mmol) was stirred with an excess of freshly distilledcyclopentadiene and BHA (5 mg) in a 5 ml round bottomed askfor 8 h. The crude product was concentrated and puried by ashcolumn chromatography on silica gel using 14% ethyl acetate inlight petroleum as the eluent to aord the cycloadduct 6 (67.5 mg,99%) as a yellowish oil, identical (IR, 1H and 13C NMR) to thecompound prepared previously.6Financial support from the Research Grant Council(HKBC 136/94P) and Faculty Research Grant (FRG/95-96/II-29) are gratefully acknowledged.Received, 15th January 1998; Accepted, 11th February 1998Paper E/8/00420JReferences1 W.Curruther, Cycloaddition in Organic Synthesis, PergamonPress New York, 1990.2 A.W. M. Lee, W. H. Chan and M. S. Wong, J. Chem. Soc.,Chem. Commun., 1988, 1585.3 A. W. M. Lee, W. H. Chan, F. Y. Ji and W. H. Poon, J. Chem.Res. (S), 1995, 368.4 A. W. M. Lee, W. H. Chan and T. T. Chan, J. Chem. Soc.,Perkin Trans. 1, 1992, 309, 945; W. H. Chan, A. W. M. Lee andT. Y. Lee, J. Chem. Soc., Perkin Trans 1, 1994, 2355.5 W. H. Chan, A. W. M. Lee and L. Jiang, Tetrahedron Lett.,1995, 36, 715; A. W. M. Lee, W. H. Chan and T. Mo,Tetrahedron Lett., 1997, 38, 3001.6 W. H.Chan, A. W. M. Lee and K. M. Lee, J. Chem. Res. (S),1994, 138.7 A. W. M. Lee, W. H. Chan, L. S. Jiang and K. W. Poon, Chem.Commun., 1997, 611.8 K. Tanake, in The Chemistry of Sulphonic Acids, Esters andTheir Derivatives, ed. S. Patai and Z. Rappoport, Wiley, NewYork, 1991, 401.9 H. Distler, Angew. Chem., Int. Ed. Engl., 1965, 4, 300; L. L.Klein and T. M. Deeb, Tetrahedron Lett., 1985, 26, 3935.10 P. Metz, M. Fleischer and R. Fro hlich, Tetrahedron, 1995, 51,711.11 J. K. Whitesell, Chem. Rev., 1992, 92, 953.12 J. Kenyon, H. Phillips and F. M. H. Taylor, J. Chem. Soc.,1933, 173; W. Gerrard, J. Kenyon and H. Phillips, J. Chem.Soc., 1937, 153; R. M. Coates and J. P. Chen, Tetrahedron Lett.,1969, 2705.13 Y. Gao and K. B. Sharpless, J. Am. Chem. Soc., 1988, 110,7538.Table 1 Diels¡ÓAlder reactions of compound 4Diene Conditions (yield) AdductCH2Cl2, 0 8C8 h (99%)benzene, 80 8C30 h (94%)benzene, 60 8Ca9 h (65%)benzene, 80 8C11 h (78%)benzene, 50 8Ca37 h (57%)bbenzene, 50 8Ca60 h (64%)baSealed tube. bMixture of regeoisomers.J. CHEM. RESEARCH (S), 1998 327

ISSN:0308-2342    

DOI:10.1039/a800420j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

An Experimental and Calculated Study ofIntramolecular Hydrogen Atom Transfer inDiethylene Glycol Bis(Allyl Carbonate)$Asfia Qureshi and Carl H. Schiesser*School of Chemistry, The University of Melbourne, Parkville, VIC 3052, AustraliaDeuterium labeling experiments and molecular orbital (MNDO) calculations indicate that 1,6-homolytic hydrogentransfer from C8 to C3 is not responsible for the products observed when diethylene glycol bis(allyl carbonate) is treatedwith tert-butoxyl radicals in the presence of 1',1',3',3'-tetramethylisoindolinyl-2'-oxyl.As part of ongoing studies into the polymerizationchemistry of diethylene glycol bis(allyl carbonate) 1a,1,2 wereported recently that reaction of 1a with tert-butoxyl rad-ical, generated through thermal decomposition of di-tert-butylperoxalate, in the presence of 1',1',3',3'-tetramethyl-isoindolinyl-2'-oxyl, gave rise to products resulting fromhydrogen atom abstraction at C8, rather than the expectedposition, namely C3.MNDO calculations provide strongsupport that abstraction at C8 is the kinetically preferredpathway, while the thermodynamic product is that arisingfrom abstraction at C3.2 In order to rule out the possibilitythat products at C8 were arising by initial abstractionat C3 followed by intramolecular homolytic hydrogen trans-fer of a C8 hydrogen to a radical centre at C3, it seemedappropriate to explore the analogous chemistry of deuter-ium-labelled diethylene glycol bis(allyl carbonate) 1b.Wenow report that reaction of 1b with tert-butoxyl radicalsleads exclusively to products in which deuterium is retainedat C3; a result consistent with (MNDO) molecular orbitalcalculations.Deuteriated allyl alcohol 2 was prepared according tothe methods of Wawzonek and Hallum3 and Salomonand Reuter.4 This was then treated with N,N'-carbonyl-diimidazole and the product 3 subsequently treated withdiethylene glycol to give 1b (Scheme 1). Treatment of 1bwith tert-butoxyl radicals, generated from di-tert-butylperox-alate, in the presence of a 10% excess of the known radicalscavenger 1',1',3',3'-tetramethylisoindolinyl-2'-oxyl5 (TMIO,ca. 0.2 M) at 608C for 70 min aorded a single major UVabsorbing peak upon analysis by HPLC.Preparativereversed-phase HPLC aorded 4b. The structure wasdeduced from 1H NMR spectroscopy and by comparisonwith a similar product 4a obtained previously from 1a.2 Theonly dierence in the 1H NMR spectra of the two com-pounds was the absence of the peaks at d 4.62 and 4.66 dueto the allylic protons in the spectrum of 4a which are notpresent for 4b (Fig. 1). These results indicate that intra-molecular hydrogen abstraction from C8 by a radicalat C3 had not taken place. Thus C8 of diethylene glycolbis(allyl carbonate) is the initial site of hydrogen atomabstraction in this reaction.This experimental study was complemented by an MNDOstudy. The transition state for hydrogen atom abstractionfrom C8 by the radical at C3 was located and is displayedin Fig. 2. The activation energy DE% for this transformationwas calculated to be 33.2 kcal mol£¾1. Given well estab-lished log A values for intramolecular 1,6-hydrogen transfer[log (A/s£¾1) 8.5¡Ó10],6 it would seem that intramolecularhydrogen transfer is not competitive with the near diusion-controlled trapping (kT=1109M£¾1 s£¾1)7 of the radicalformed at C3 by 1',1',3',3'-tetramethylisoindolinyl-2'-oxyl.%On the basis of these data, even if abstraction at C3 werecompetitive with abstraction at C8, it is highly unlikely thatthe intramolecular process would lead to the radical at C8.The origin of the kinetic preference for hydrogen abstractionat C8 over C3 has been discussed previously2 and attributedto the greater conjugative stabilizing inuence of the etheroxygen (a-eect)8 combined with the possible additionalstabilization aorded by the carbonate oxygen (b-eect)9 onthe radical at C8 than the similar combined eects of olenand carbonate oxygen on the radical at C3.In summary, both deuterium labelling experimentsand MNDO calculations indicate that intramolecular 1,6-J.Chem. Research (S),1998, 328¡Ó329$Scheme 1 Reagents and conditions: i, THF, 1 h;ii, (a) pyridine¡ÓCHCl3 £¾18 8C; (b) reflux, 3 h$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.%To achieve 1% rearrangement under the reactions conditionsdescribed (ca. 0.2 M in TMIO), an energy barrier of less than about3¡Ó5 kcal mol£¾1 would be required.328 J. CHEM. RESEARCH (S), 1998hydrogen transfer chemistry is not involved in the formationof products obtained when diethylene glycol bis(allyl car-bonate) 1a is treated with tert-butoxyl radicals derivedfrom di-tert-butylperoxalate in the presence of 1',1',3',3'-tetramethylisoindolinyl-2'-oxyl.ExperimentalPreparation of Compound 3.To N,N'-carbonyldiimidazole(8.01 g, 0.049 mol) in freshly distilled THF (30 ml) was added com-pound 2 (2.97 g, 0.049 mol) dropwise with stirring.The mixture wasstirred for 1 h, transferred to a separatory funnel, washed withwater (210 ml) and dichloromethane (210 ml), dried (Na2SO4)and the solvent evaporated. Distillation of the crude materialaorded 3 (7.45 g, 99%), bp 78 8C/15 mmHg. IR (lm) max/cm£¾11756, 1648, 1318, 1297, 1245 H (CDCl3, 300 MHz) 5.25 (d, 1 H,H1a, J 10.3), 5.33 (d, 1 H, H1b, J 17.3 Hz), 5.89 (m, 1 H, H2), 6.94(s, 1 H, H10), 8.03 (s, 1 H, H7).C (75 MHz) 68.3 (C3), 116.8(C10), 119.9 (C1), 130.1 (C2), 130.3 (C9), 136.8 (C7), 148.1 (C5).N (30 MHz) 185 (N6), 265 (N8). m/z 154 (M, 62), 109 (90),58 (100%). Accurate mass m/z 154.0714 (C7H6D2N2O2 requires154.0711).Preparation of Compound 1b.Diethylene glycol (2.32 ml,0.0245 mol) was added to pyridine (2.2 ml, 0.027 mol) and chloro-form (30 ml) at £¾18 8C, followed by a mixture of compound 3 inchloroform (7.45 g, 0.049 mol).The mixture was reuxed for 3 h,then transferred to a beaker of distilled water (75 ml), acidied withconcentrated HCl and extracted with dichloromethane (350 ml).The crude residue was subjected to ash chromatography followedby distillation to yield 1b (3.88 g, 57%), bp 166¡Ó168 8C/2 mmHg IR(lm) max/cm£¾1 2953, 1742, 1641, 1276, 113.8. H (CDCl3,300 MHz) 3.72 (m, 4 H, H8, H10), 4.29 (m, 4 H, H7, H11), 5.26 (d,2 H, H1a, H17a, J 10.5), 5.36 (d, 2 H, H1b, H17b, J 17.1 Hz), 5.90(dd, 2 H, H2, H16, J 17.1, 10.5 Hz). C (75 MHz) 66.8 (C7, C11),68.9 (C8, C10), 72.4 (C3, C15), 119.1 (C1, C17), 131.3 (C2, C16),160.6 (C5, C13).m/z 279.Reaction of Compound 1b with tert-Butoxyl in the Presenceof 1',1',3',3-Tetramethylisoindolinyl-2'-oxyl.A solution of com-pound 1b (2.036 g, 7.24 mmol), di-tert-butylperoxalate (40.91 mg,0.18 mmol) and 1',1',3',3'-tetramethylisoindolinyl-2'-oxyl (69.33 mg,0.4 mmol) was degassed by repeated freeze/thaw cycles, sealedin vacuo and heated in a water-bath at 60 8C for 70 min.Thereaction mixture was analysed by HPLC. The major reaction pro-duct 4b was isolated and characterized by 1H NMR spectroscopy.H (CDCl3, 400 MHz) 1.35¡Ó1.55 (4 br s, 12 H, ring methyls), 3.93(ddd, 1 H, H10b, J 11.5, 6.2, 4.1), 4.16 (ddd, 1 H, H10a, J 11.7,5.1, 4.1), 4.22 (dd, 1 H, H7a, J 11.5, 5.1), 4.25 (dd, 1 H, H7b, J11.5, 6.2), 4.30 (ddd, 2 H, H11, J 7.3, 5.4, 3.9), 5.12 (dd, 1 H, H8, J6.1, 5.4), 5.26 (ddd, 1 H, H17a, J 10.4, 2.7, 1.2 Hz), 5.28 (ddd, 1 H,H1a, J 10.5, 2.7, 1.2 Hz), 5.36 (ddd, 1 H, H17b, J 17.1, 2.9, 1.5),5.38 (ddd, 1 H, H1b, J 17.3, 2.9, 1.5), 5.94 (m, 2 H, H2, H16), 7.09(dd, 2 H, H4', H7', J 5.1, 2.7), 7.23 (dd, 2 H, H5', H6', J 5.4,2.9 Hz).Molecular Orbital Calculations.Molecular orbital calculationswere performed at the unrestricted Hartree¡ÓFock (UHF) levelfor open-shell species using MNDO in MOPAC version 6.10 Struc-tures were optimized to minima using the BFGS11 method or totransition states using the eigenvector following (EF) algorithm12 ona Sun Sparcstation 2 computer.Financial support from the University of Melbourne (toA.Q.) and the Australian Research Council is gratefullyacknowledged.Received, 30th September 1997; Accepted, 11th February 1998Paper E/7/07048IReferences1 A. Qureshi, D.H. Solomon and D. P. Kelly, Eur. Polym, J.,1995, 31, 809.2 A. Qureshi, C.H. Schiesser and D. H. Solomon, Eur. Polym. J.,1996, 32, 85.3 S. Wawzonek and J. V. Hallum, J. Org. Chem., 1953, 18, 288.4 R. G. Salomon and J. M. Reuter, J. Am. Chem. Soc., 1977, 99,4372.5 E. Rizzardo and D. H. Solomon, Polym. Bull., 1979, 1, 529.6 Landolt-Bornstein, Numerical Data and Functional Relationshipsin Science and Technology, ed. H. Fischer, Springer, Berlin,1994, vol. II/18; S. W. Benson, Thermochemical Kinetics, Wiley,New York, 1968; J. A. Franz, D. H. Roberts and K. F. Ferris,J. Org. Chem., 1987, 52, 2256.7 A. L. J. Beckwith and V. W. Bowry, J. Org. Chem., 1988, 53,1632.8 V. Malatesta and J. C. Scaiano, J. Org. Chem., 1982, 47, 1455.9 D. H. R. Barton, W. Hartwig and W. B. Motherwell, J. Chem.Soc., Chem. Commun., 1982, 447.10 M. J. S. Dewar and W. Thiel, J. Am. Chem. Soc., 1977, 99,4907, 4899.11 C. G. Broyden, J. Inst. Math. Appl., 1970, 6, 222; R. Fletcher,Comput. J., 1970, 13, 317; D. Goldfard, Math. Comput., 1970,24, 23; D. F. Shanno, Math. Comput., 1970, 24, 647.12 J. Baker, J. Comput. Chem., 1986, 7, 385.Fig. 1 1H NMR Spectra of the allylic region of compounds4a (above) and 4b (below)Fig. 2 MNDO Calculated transition state for hydrogen atomabstraction by C3 from C8J. CHEM. RESEARCH (S), 1998 329

ISSN:0308-2342    

DOI:10.1039/a707048i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Improved Synthesis of 2-Amino-3-cyanopyridinesin Solvent Free Conditions under MicrowaveIrradiation$Satya Paul,a Rajive Gupta*a and Andre LoupybaDepartment of Chemistry, University of Jammu, Jammu 180006, IndiabLaboratoire des Reactions Selectives sur Supports ICMO, UA 478 Batiment 410,Universite de Paris - Sud, 91405 ORSAY, Cedex, FranceA simple and efficient method is developed for the rapid synthesis of 2-amino-3-cyanopyridines 3¡Ó5 from arylidenemalanonitriles1 and ketones 2 or 4 in presence of ammonium acetate without solvent/containing traces of solvent undermicrowave irradiation : reaction times are considerably reduced with improved yields as compared to those obtainedunder classical heating.Organic synthesis under microwave irradiation is nowwidely used.1¡Ó3 Dry media techniques by microwave heatinghave attracted much attention4¡Ó6 and oers several advan-tages: solvents are often expensive, toxic, dicult to removein case of aprotic dipolar solvents with high boiling points,and are agents that pollute the environment.Liquid¡Óliquidextraction is avoided for the isolation of the reaction pro-ducts. The absence of solvent also reduces the risk ofhazardous explosions when the reaction takes place in aclosed vessel in the microwave oven.The preparation of 2-amino-3-cyanopyridines continuesto be the subject of numerous papers as these are versatileintermediates for the synthesis of variety of heterocycliccompounds.7¡Ó9 Many of the standard procedures10¡Ó12require either longer reaction times or in some cases lead tomixtures of products and proceed in low yields.Keeping in view the importance of 2-amino-3-cyano-pyridines and recent trends of phasing out the use oforganic solvents and devising environmentally-friendly tech-niques, we report the synthesis of 2-amino-3-cyanopyridines3¡Ó5 from arylidenemalanonitriles 1 and ketones 2 or 4 in thepresence of ammonium acetate using microwaves withoutsolvent or containing traces of solvent.In the classical approach, the synthesis of 3 or 5 requires5¡Ó8 h reuxing in benzene.In contrast, the same reactionwhen performed under microwave irradiation required3¡Ó5 min and improvement in yields was also observed. Thework-up is simply reduced to treatment with ethanol, whichon standing gave 2-amino-3-cyanopyridines as crystallineproducts.The amount of ammonium acetate and power outputwas adjusted to get the maximum yield of the products3 or 5.By carrying out reactions with dierent amountsof ammonium acetate at dierent power outputs, it hasbeen found that 8 mmol of the ammonium acetate furnishedthe maximum yield for 1 mmol of the reactants, whenirradiated at a power output of 275 W. Furthermore, ithas been found that if o-dichlorobenzene (0.5 ml) was addedto the reactants (3 mmol), the yields increase considerablye.g. in 5b it increases from 50 to 78%. The addition ofJ. Chem. Research (S),1998, 330¡Ó331$Table 1 Analytical and spectral data of compounds 5Compound Mp (8C) Ma umax/cm£¾1 dHb m/z (%)5a 169¡Ó170 C20H15N3 3420, 3350, 3175, 2210 2.55¡Ó2.95 [m, 4 H, (CH2)2], 5.20¡Ó5.50 (br s,2 H, NH2) 7.00¡Ó7.80 (m, 9 H, aryl H)297 (100)5b 164¡Ó165 C21H17N3O 3450, 3350, 3150, 2220 2.60¡Ó3.0 [m, 4 H, (CH2)2], 3.85¡Ó3.95 (s,3 H, OCH3), 5.25¡Ó5.35 (br s, 2 H, NH2),6.95¡Ó7.60 (m, 8 H, aryl H)327 (100)5c 215¡Ó216 C22H19N3O2 3450, 3310, 3180, 2210 1.50¡Ó1.57 (t, 3 H, £¾CH3), 3.60¡Ó3.66 (s, 2 H,£¾CH2), 3.90¡Ó3.98 (s, 3 H, OCH3), 4.20¡Ó4.28 (q, 2 H, OCH2), 5.25¡Ó5.32 (br s, 2 H,NH2), 6.98¡Ó7.60 (m, 7 H, aryl H)357 (100)5d 208¡Ó209 C23H21N3O3 3430, 3330, 3150, 2200 1.50¡Ó1.60 (t, 3 H, CH3), 3.60¡Ó3.65 (s, 2 H,CH2), 3.90¡Ó4.0 (s, 6 H, 2OCH3), 4.20¡Ó4.30 (q, 2 H, OCH2), 5.30¡Ó5.38 (br s, 2 H,NH2), 6.95¡Ó7.55 (m, 6 H, aryl H)387 (100)aAll the compounds gave C, H and N analyses within20.5%.bThe 1H NMR spectra were recorded in CDCl3.Scheme 1$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [J.Chem. Research (S), 1998, Issue 1]; there is thereforeno corresponding material in J. Chem. Research (M).*To receive any correspondence.330 J. CHEM. RESEARCH (S), 1998o-dichlorobenzene as an energy-transfer medium is to permit a higher temperature and better homogeneity in the reaction medium. In order to study the possible existence of a speci¢çc microwave e€ect, we have carried out all the reactions using the conventional heating mode (oil bath) at the same ¢çnal temperatures and reaction times as measured in the micro- wave experiments. In all cases no reactions were detected as determined by TLC.Lower yields were obtained with the conventional heating mode, even after 4 h of reaction, indi- cating that the e€ect of microwave irradiation is not purely thermal. The title compounds were characterised on the basis of analytical, spectral data and by comparison with authentic samples prepared by known methods12 (Table 1).The reac- tion pathway is shown in Scheme 1. The reaction times and yields using microwave and conventional methods have been compared (Table 2). Experimental Melting points were determined in open capillaries on a Toshniwal melting point apparatus and are uncorrected. The reac- tions were monitored by means of TLC, IR spectra (umax in cm¢§1) were recorded on a Shimadzu-435 spectrophotometer using KBr discs and 1H NMR spectra in CDCl3 and CDCl3¡¾[2H6]DMSO on Varian EM-390 (90 MHz) or Bruker AM-250 (250 MHz) spec- trometers.The compound SiMe4 was used as an internal standard; the chemical shifts are expressed in d down¢çeld from SiMe4. The mass spectra were performed on a Delsi/Nermag spectral 30 spectrometer. Reactions were carried out in a BMO-700 T domestic microwave oven manufactured by BPL multimode Sanyo utilities and Appliances Ltd., Bangalore operating at 2450 MHz at a maximum power of 650 W. General procedure for the synthesis of 2-amino-3-cyanopyridines.�¢A mixture of arylidenemalanonitrile 1 (3 mmol), ketone 2 or 4 (3 mmol), ammonium acetate (24 mmol) and o-dichlorobenzene (0.5 ml) was placed in a borosil beaker (100 ml) and mixed thoroughly with the help of a glass rod. The mixture was then sub- jected to microwave irradiation for an optimized time (Table 2) at a power output of 275 W. After completion of the reaction (moni- tored by TLC), ethanol (4 ml) was added to the reaction mixture and kept at room temperature for 5¡¾10 min, the crystalline product obtained was ¢çltered, washed with ethanol and recrystallised from the appropriate solvent (benzene, light petroleum (bp 40¡¾60 8C)¡¾ ethanol or tetrahydrofuran).The analytical and spectral data of 5a¡¾5d are given in Table 1 while 3a¡¾3d were characterised by their literature melting points.12 In conclusion, we have developed a simple, e.cient and environmentally friendly method for the synthesis of 2-amino-3- cyanopyridines using an unmodi¢çed domestic microwave oven.Yields were enhanced by addition of a small amount of solvent, here o-dichlorobenzene. One of us (S. P.) thanks the CSIR, New Delhi for the award of a senior research fellowship. Received, 25th November 1997; Accepted, 25th February 1998 Paper E/7/08521D References 1 R. A. Abramovitch, Org. Prep. Proced. Int., 1991, 23, 685. 2 S. Caddick, Tetrahedron, 1995, 51, 10403. 3 S. A. Galema, Chem. Soc. Rev., 1997, 26, 223. 4 A. Loupy, G. Gram and J. Sansoulet, New J. Chem., 1992, 16, 223; A. Loupy, A. Petit and B. Bonnet-Delpom, J. Fluorine Chem., 1995, 95, 15. 5 A. Loupy, A. Petit, M. Ramdani, C. Yvanae€, M. Majdoub, B. Labiad and D. Villemin, Can. J. Chem., 1993, 71, 90; R. S. Varma, R. Dahiya and S. Kumar, Tetrahedron Lett., 1997, 38, 5131. 6 D. Bogda J. Pielichowski and K. Jaskot, Heterocycles, 1997, 45, 715; D. Villemin and M. Hammadi, Synth. Commun., 1996, 26, 4337. 7 K. Doe, K. Avasthi, R. Pratap, D. S. Bakuni and M. N. Joshi, Indian J. Chem., Sect. B, 1990, 29, 459. 8 C. J. Shishoo, M. B. Devani, V. S. Bhadti, S. Ananthan and G. V. Ullas, Tetrahedron Lett., 1983, 24, 4611. 9 L. I. Ibrahiem, G. H. Tammam and T. M. S. Abdin, J. Chem. Soc. Pak., 1989, 11, 227; P. L. Barili, G. Biagi, O. Livi, L. Mucci and V. Scartoni, J. Heterocycl. Chem., 1987, 24, 997. 10 A. A. Fadda, Indian J. Chem., Sect. B, 1991, 30, 28. 11 L. Prakash, Shaihla, S. Malik and R. L. Mittal, Curr. Sci., 1989, 58, 967. 12 S. Kambe, K. Saito, A. Sakurai and H. Midorikawa, Synthesis, 1980, 366. Table 2 Comparison of reaction times and yields for compounds 3 and 5 using microwave and classical methods Reaction time Yield (%) Microwave (min) Microwave Compound Without solvent Trace solvent Classical reflux with benzene (h) Without solvent Trace solvent Classical 3a 4.0 3.0 5 52 72 49 3b 4.0 3.5 6 43 75 46 3c 4.5 3 5.5 58 78 69 3d 3.5 3.5 6 52 69 46 5a 4.0 4.0 5.5 51 70 52 5b 4.5 4.0 6 50 78 55 5c 4.0 3.5 6 42 72 46 5d 4.5 3.5 5.5 52 70 48 J. CHEM. RESEARCH (S), 1998 331

ISSN:0308-2342    

DOI:10.1039/a708521d

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Efficient Synthesis of 3-Arylphthalides$Madhusudhan V. Paradkar,* Anup A. Ranade, Madhuri S. Kulkarni,Himanshu M. Godbole and Augustine R. JosephDepartment of Chemistry, Post Graduate & Research Centre, A.G. College, Karve Road,Pune 411 004, IndiaA convenient method for the synthesis of 3-arylphthalides (3a¡Óq) involving condensation of phthalaldehydic acids(1a,b) with aromatic substrates (2a¡Ók) in the presence of TFA is described.Phthalides, isobenzofuran-1(3H)-ones, constitute an import-ant class of naturally occurring oxygen ring compounds,well known for their interesting biological properties.1 Theyare also used as intermediates for the synthesis of iso-coumarins,2 anthraquinones3 and anthracyclines.4 In viewof this, various methods have been reported for theirsynthesis.As a part of our ongoing programme directed towardsthe synthesis of various naturally occurring and biologicallyactive anthraquinones, we needed 3-arylphthalides asprecursors for their synthesis.Most methods reported forthe synthesis of 3-arylphthalides involve (i) heteroatom-directed lithiation of benzamides, followed by reaction withan appropriate aryl aldehyde as an electrophile,5 (ii) reactionof phthalaldehydic acids with arylmagnesium halides6 and(iii) acid-catalysed condensation of phthalaldehydic acidswith aromatic substrates.7¡Ó9 Method (iii) in the presenceof an acid appeared to us more convenient as it does notinvolve sensitive organometallic reagents and critical reac-tion conditions.The acids used were sulfuric acid7 in dier-ent concentrations, concentrated hydrochloric acid8 andmethanesulfonic acid9 (MSA).Even though the yields of 3-arylphthalides were moderateby using sulfuric acid, the experimental conditions variedfrom substrate to substrate; for example, in some cases con-centrated sulfuric acid was used while in others a mixture ofsulfuric acid with oleum was used. Furthermore in somecases a mixture of isomeric phthalides was obtained.MSAwas used for condensation of naphthalene and its monosub-stituted derivatives only and the reaction required stirringovernight.It was therefore decided rst to use concentrated hydro-chloric acid. Adopting the reported procedure,8 when hydro-quinone dimethyl ether and resorcinol dimethyl ether weretreated with phthalaldehydic acid 1a10 in the presence ofconcentrated hydrochloric acid the corresponding phthalides3b and 3a were obtained in 50¡Ó55% yield. Both reactionsrequired 2 h for completion and steam distillation to obtainpure products.Hence it was decided to look for anotherreagent which would be general and could provide the nalproducts in high yields and shorter reaction times.As triuoroacetc acid (TFA), having good ionizing powerand very low nucleophilicity, has been used as a reagent forelectrophilic aromatic substitution reactions,11 it was thusdecided to use TFA (Scheme 1). As a test case, when asolution of phthalaldehydic acid 1a and resorcinol dimethylether 2a in TFA was heated on water-bath the reaction wascomplete in 15 min as evident from TLC and the desiredphthalide 3a, mp 105 8C (lit.,8 106 8C) was obtained in 90%yield. Similarly when hydroquinone dimethyl ether 2b wascondensed with 1a it provided the phthalide 3b, mp 808C(lit.,8 80 8C) in 85% yield.With these encouraging results,various other aromatic substrates were subjected to con-densation with 1a and the corresponding phthalides 3a¡Ókwere obtained in 80¡Ó85% yield using TFA.Compound 1b12on similar reaction with aromatic substrates provided thecorresponding phthalides 3l¡Óq. The starting acid 1b wasobtained by hydrolysis of ethyl 2-formyl-3,5-dimethoxy-benzoate which in turn was obtained by formylation of ethyl3,5-dimethoxybenzoate using Vilsmeier¡ÓHack reaction.To conclude, the present paper describes a simple andecient method for the synthesis of 3-arylphthalides. Themajor advantages of TFA over other acid-catalysed methodsare (i) the desired phthalides are obtained in high yields,(ii) the work-up procedure is simple and (iii) milder reactionconditions are required.ExperimentalAll melting points are uncorrected. 1H NMR spectra wererecorded on a JEOL FX 90 Q instrument in CDCl3 using TMS asinternal standard, IR spectra on a Perkin Elmer FT IR 1600spectrophotometer. All compounds gave satisfactory microanalysis(20.2% for C and H).General Procedure.A solution of phthalaldehydic acid 1(0.002 mol), aromatic substrate 2 (0.002 mol) and TFA (1 ml) washeated on water-bath for 15 min.The reaction mixture was cooledand poured on crushed ice. The solid thus obtained was ltered oand puried by column chromatography using hexane¡Óethyl acetate(9:1) as an eluent.3a. R=R2=R4=H; R1=R3=OCH3 (90% yield); mp 105 8C(lit.,8 106 8C); ~max/cm£¾1 (Nujol) 1750 (lactone carbonyl); dH 3.70(s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 6.55 (s, 1 H, CH), 6.85 (s, 1 H,H-Ar), 7.10 (m, 1 H, H-Ar), 7.60¡Ó8.00 (m, 4 H, H-Ar), 8.20 [br d1 H (J=8 Hz), H-Ar].3b. R=R2=R3=H; R1=R4=OCH3 (75% yield); mp 80 8C(lit.,8 80 8C); ~max/cm£¾1 (Nujol) 1750 (lactone carbonyl); dH 3.70(s, 3 H, OCH3) 3.90 (s, 3 H, OCH3), 6.65 (s, 1 H, CH), 6.80¡Ó7.00(m, 3H, H-Ar), 7.40¡Ó7.70 (m, 3 H, H-Ar), 7.95 [br d 1 H (J=8 Hz),H-Ar].J.Chem. Research (S),1998, 332¡Ó333$Scheme 1$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [J. Chem. Research (S), 1998, Issue 1]; there is thereforeno corresponding material in J.Chem. Research (M).*To receive any correspondence.332 J. CHEM. RESEARCH (S), 19983c. R=R1=R4=H; R2=R3=OCH3 (90% yield); mp 146 8C (lit.,13 148 8C); ~max/cm¢§1 (Nujol) 1760 (lactone carbonyl); dH 3.90 (s, 3 H, OCH3) 4.00 (s, 3 H, OCH3), 6.55 (s, 1 H, CH), 6.90 (br s, 1 H, H-Ar), 7.05 (m, 1 H, H-Ar), 7.30¡¾8.00 (m, 4 H, H-Ar), 8.15 [br d 1 H (J=8 Hz), H-Ar]. 3d. R=R2=R3=H; R1=OCH3; R4=CH3 (85% yield); mp 118 8C (lit.,7b 121 8C); ~max/cm¢§1 (Nujol) 1755 (lactone carbonyl); dH 2.20 (s, 3 H, CH3), 3.90 (s, 3 H, OCH3), 6.80¡¾6.90 (m, 2 H, CH, H-Ar), 7.10 [d (J=2), 1 H, H-Ar], 7.30¡¾7.65 (m, 4 H, H-Ar), 7.95 [br d (J a 8 Hz), H-Ar]. 3e. R=R2=R4=H; R1=CH3; R3=OCH3 (75% yield); mp 121 8C; ~max/cm¢§1 (Nujol) 1750 (lactone carbonyl); dH 2.50 (s, 3 H, CH3) 3.85 (s, 3 H, OCH3), 6.55¡¾7.05 (m, 3 H, CH, H-Ar), 7.45 [d (J=8), 1 H, H-Ar], 7.55¡¾7.95 (m, 3 H, H-Ar), 8.10 [br d (J=8 Hz), 1 H, H-Ar]. 3f. R=R2=H; R1=R4=OCH3; R3=CH3 (85% yield); mp 138 8C; ~max/cm¢§1 (Nujol) 1765 (lactone carbonyl); dH 2.25 (s, 3 H, CH3) 3.85 (s, 3 H, OCH3), 3.95 (s, 3 H, OCH3), 6.65 (s, 1 H, CH), 6.95 (br s, 2 H, H-Ar), 7.50¡¾7.85 (m, 3 H, H-Ar), 8.20 [br d (J=8 Hz), 1 H, H-Ar]. 3g. R=R2=H; R1=CH3; R3=R4=OCH3 (80% yield); mp 102 8C; ~max/cm¢§1 (Nujol) 1765 (lactone carbonyl); dH 2.50 (s, 3 H, CH3), 3.70 (s, 3 H, OCH3), 3.90 (s, 3 H, OCH3), 6.30 (s, 1 H, CH), 6.65 (s, 1 H, H-Ar), 6.75 (s, 1 H, H-Ar), 7.35 [br d (J=8), 1 H, H-Ar], 7.55¡¾7.75 (m, 2 H, H-Ar), 8.00 [br d (J=8 Hz), 1 H, H-Ar]. 3h. R=H; R1=R4=OCH3; R2, R3=[CH2]4 (75% yield); oil; ~max/cm¢§1 (Nujol) 1755 (lactone carbonyl); dH 1.80¡¾2.10 (m, 4 H, 2CH2), 2.50¡¾3.00 (m, 4 H, 2CH2), 3.70 (s, 3 H, OCH3), 3.90 (s, 3 H, OCH3), 6.25 (s, 1 H, CH), 6.90 (s, 1 H, H-Ar), 7.40¡¾7.80 (m, 3 H, H-Ar), 8.05 [br d (J=Hz), 1 H, H-Ar]. 3i. R=H; R1=R4=OCH3; R2=R3=CH1CH0CH1CH (80% yield); mp 143 8C ~max/cm¢§1 (Nujol) 1750 (lactone carbonyl); dH 3.75 (s, 3 H, OCH3), 4.05 (s, 3 H, OCH3), 6.15 (s, 1 H, CH), 7.05 (s, 1 H, H-Ar), 7.35¡¾7.70 (m, 5 H, H-Ar), 7.90¡¾8.15 (m, 2 H, H-Ar), 8.25 [br d (J=8 Hz), 1 H, H-Ar]. 3j. R=R3=R4=H; R1, R2=CH1CH0CH1CH (85% yield); mp 135 8C (lit.,9 137 8C); ~max/cm¢§1 (Nujol) 1750 (lactone carbonyl); dH 6.50 (s, 1 H, CH), 7.10¡¾8.00 (complex multiplet, 10 H, H-Ar), 8.20 [br d (J a 8 Hz), 1 H, H-Ar]. 3k. R=R1=R2=R4=H; R3=OCH3 (85% yield); mp 117 8C (lit.,13 118 8C); ~max/cm¢§1 (Nujol) 1760 (lactone carbonyl); dH 3.90 (s, 3 H, OCH3), 6.50 (s, 1 H, CH), 7.10¡¾7.90 (m, 7 H, H-Ar), 8.15 [br d (J a 8 Hz), 1 H, H-Ar]. 3l. R=R2=R3=OCH3; R1=R4=H (85% yield); mp 119 8C; ~max/cm¢§1 (Nujol) 1760 (lactone carbonyl); dH 3.85 (s, 3 H, OCH3), 3.90 (s, 3 H, OCH3), 3.95 (s, 6 H, 2OCH3), 6.40 (s, 1 H, CH), 6.65¡¾7.05 (m, 4 H, H-Ar), 7.10 [d (J a 2 Hz), 1 H, H-Ar]. 3m. R=R1=R3=OCH3; R2=R4=H (85% yield); mp 162 8C; ~max/cm¢§1 (Nujol) 1750 (lactone carbonyl); dH 3.75 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 3.90 (s, 3 H, OCH3), 3.95 (s, 3 H, OCH3), 6.30¡¾6.60 (m, 2 H, CH, H-Ar), 6.65¡¾6.90 (m, 3 H, H-Ar), 7.05 [d (J a 2 Hz), 1 H, H-Ar]. 3n. R=R1=R4=OCH3; R2=R3=H (80% yield); mp 149 8C; ~max/cm¢§1 (Nujol) 1760 (lactone carbonyl); dH 3.70 (s, 3 H, OCH3), 3.80 (s, 3 H, OCH3), 3.90 (s, 3 H, OCH3), 3.95 (s, 3 H, OCH), 6.55 (s, 1 H, CH), 6.65¡¾7.05 (m, 4 H, H-Ar), 7.10 [d (J a 2 Hz), 1 H, H-Ar]. 3o. R=R1=R4=OCH3; R2=H; R3=CH3 (80% yield); mp 149 8C; ~max/cm¢§1 (Nujol) 1765 (lactone carbonyl); dH 2.25 (s, 3 H, CH3), 3.65 (s, 3 H, OCH3), 3.75 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 3.95 (s, 3 H, OCH3), 6.40 (s, 1 H, CH), 6.70¡¾7.00 (m, 3 H, H-Ar), 7.10 [d (J a 2 Hz), 1 H, H-Ar]. 3p. R=R3=R4=OCH3; R1=CH3; R2=H (80% yield); mp 172 8C; ~max/cm¢§1 (Nujol) 1760 (lactone carbonyl); dH 2.50 (s, 3 H, CH3), 3.70 (s, 3 H, OCH3), 3.75 (s, 3 H, OCH3), 3.95 (s, 6 H, 2OCH3), 6.35 (s, 1 H, CH), 6.60 (s, 1 H, H-Ar), 6.70¡¾6.90 (m, 2 H, H-Ar), 7.10 [d (J a 2 Hz), 1 H, H-Ar]. 3q. R=R1=R4=OCH3; R2, R3=[CH2]4 (75% yield); mp 193 8C; ~max/cm¢§1 (Nujol) 1755 (lactone carbonyl); dH 1.50¡¾2.05 (m, 4 H, 2CH2), 2.45¡¾3.00 (m, 4 H, 2CH2), 3.60 (s, 3 H, OCH3), 3.75 (s, 3 H, OCH3), 3.90 (s, 3 H, OCH3), 4.00 (s, 3 H, OCH3), 6.15 (s, 1 H, CH), 6.70¡¾7.00 (m, 2 H, H-Ar), 7.15 [d (J a 2 Hz), 1 H, H-Ar]. We thank Dr A. S. Inamdar, Principal, A.G. College, Pune for providing the necessary facilities, Professor R. S. Mali, University of Pune for useful discussions and University of Pune for the spectral and elemental analysis.H. M. Godbole (SRF) and A. R. Joseph (JRF) thank CSIR for ¢çnancial assistance. Received, 29th January 1998; Accepted, 20th February 1998 Paper E/8/00804C References 1 E. Sing and P. C. Gupta, J. Indian Chem. Soc., 1973, 50, 676. 2 N. S. Narasimhan and R. S. Mali, Synthesis, 1975, 797. 3 J. E. Baldwin and K. W. Bair, Tetrahedron Lett., 1978, 2559. 4 K. S. Kim, M. W. Spatz and F. Johnson, Tetrahedron Lett., 1979, 331. 5 W. H. Putersbaugh and C. R. Hauser, J. Org. Chem., 1964, 29, 853. 6 Fr. M 5,606, Soc. Des. Usinem Chimiques, Rhone Poulenc (Chem. Abstr., 71, P 49976c). 7 (a) V. W. Floutz, J. Org. Chem., 1960, 25, 643; (b) V. W. Floutz, J. Org. Chem., 1961, 26, 2584; (c) R. Al-Hamdany, J. M. Al-Rawi and S. Ibrahim, J. Prakt. Chem., 1987, 126. 8 E. S. Jones, W. H. Perkin Jr. and R. Robinson, J. Chem. Soc., 1912, 10, 257. 9 M. S. Newman, J. Org. Chem., 1975, 2996; M. S. Newman, V. Sankaran and D. R. Olson, J. Am. Chem. Soc., 1976, 98, 3237. 10 Org. Synth., 1955, Coll. Vol. III, 737. 11 M. S. Newman and W. M. Hung, Org. Prep. Proced. Int., 1972, 4, 227; L. L. Woods and J. Sapp, J. Org. Chem., 1964, 29, 3445; 1962, 27, 3703. 12 S. A. Kulkarni, Ph.D. Thesis, Pune University, 1995. 13 J. N. Chatterjea, H. C. Jha and A. K. Chattopadhyay, Tetrahedron Lett., 1972, 3409. J. CHEM. RESEARCH (S), 1998 333

ISSN:0308-2342    

DOI:10.1039/a800804c

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Novel Synthesis of a-Benzotriazolyl-substituted Ketones$ Alan R. Katritzky,*a Ashraf A. Abdel-Fattah,a Sergei A. Belyakova and Amine F. M. Fahmyb aCenter for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA bDepartment of Chemistry, Faculty of Science, Ain Shams University, Abbassia, Cairo, Egypt Silyl enol ethers react with 1-chlorobenzotriazole to provide a new general method for the preparation of -benzotriazolyl- substituted ketones.a-Benzotriazolyl-substituted ketones are versatile inter- mediates in the synthesis of a variety of organic compounds, including substituted acetylenes,1 3,5-diarylphenols2 and alkyl aryl ketones;3 these ketones were also used to prepare 2-arylquinoxalines, 1,4,5,6-tetrahydropyridazines,4 5-(amino-substituted)pyrid-2-ones and indolopyrid-2-ones.5 a-Benzotriazolyl-substituted ketones possess enhanced reac- tivity based on the increased acidity of the bridge proton(s) which is(are) activated by the neighbouring benzotriazole moiety and carbonyl group.Some of their reactions (e.g. of their hydrazones with metalloorganic compounds, etc.6) can not be performed using their structural analogues, a-halo ketones, because of the high lability of the C±Hal bond. Ketones bearing a benzotriazole moiety in an a-position were previously prepared by (i) reactions of a-halo ketones with benzotriazole or its sodium salt in re�uxing aprotic solvents,4±7 (ii) acylation of N-(trimethylsilylmethyl)benzo- triazole with acid chlorides3 and (iii) reactions of a-lithiated- 1-methylbenzotriazoles with aromatic or aliphatic esters.1 These methods were mostly applied to the preparation of aryl benzotriazolylmethyl ketones.We now report that reactions of 1-chloromethylbenzo- triazole with ketone silyl enol ethers represent a general method for the preparation of aliphatic, alicyclic and aromatic ketones substituted at the a-carbon atom by a benzotriazole moiety.The silyl enol ethers used were prepared by known reactions of the corresponding ketones with trimethylsilyl chloride in the presence of lithium diisopropylamide (LDA) J. Chem. Research (S), 1998, 334±335$ Table 1 Preparation of a-benzotriazole-substituted ketones 3a±l Found (calcd.) (%) Reaction mp, (t/8C) Molecular Ketone 3 time (t/h) Yield (%) (lit. mp, (t/8C) formula C H N a 3 59 111±113 C14H16N3O (112±1136) b 3 54 129±131 C15H13N3O (130±1311) c 4 56 141±143 C15H13N3O2 15.64 (67.39) (4.91) (15.73) d 4 58 157±159 C14H10BrN3O 53.27 3.11 13.24 (53.33) (3.20) (13.34) e 4 62 97±99 C15H13N3O 16.61 (71.68) (5.22) (16.73) f 5 65 158±159 C20H15N3O (161±1637) g 8 51 138±139 C13H10N4O 23.28 (65.54) (4.23) (23.52) h 6 38 101±103 C12H15N3O 66.12 6.73 19.05 (66.34) (6.96) (19.34) i 5 42 100±102 C11H13N3O 20.34 (64.99) (6.45) (20.68) j 6 52 157±159 C18H21N3O 14.16 (73.19) (7.17) (14.23) k 6 56 126±128 C15H11N3O 71.86 4.42 16.75 (72.26) (4.45) (16.87) l 10 54 142±144 C16H13N3O a aFound: m/z, 263.1058.C16H13N3O requires Mr 263.1058. Scheme 1 $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. 334 J. CHEM. RESEARCH (S), 1998(1a±e)8 or LDA±NaI for (1f±j).9 Indanone (1k) and tetra- lone (1l) silyl enol ethers were synthesized in a DMF± triethylamine mixture.10 All ethers were puri®ed by distilla- tion except 1h which was used without puri®cation.Heating neat mixtures of a ketone silyl enol ether 1a±l and 1-chlorobenzotriazole (2) at 100 8C (Scheme 1) gave the corresponding a-benzotriazolyl-substituted ketones 3a±l. These compounds were isolated by column chromatography in moderate yields (38±65%) and characterized by NMR (1H, 13C) and elemental analysis or HRMS (Table 1). Our new methodology enables the preparation of ketones of types 3 g,k,l, which previously known methods [see above, (i)±(iii)] do not allow.Experimental General Procedure for the Preparation of -Benzotriazolyl- substituted Ketones 3a±l.�A mixture of the corresponding silyl enol ether 1a±l (2 mmol) and 1-chlorobenzotriazole 2 (0.36 g, 2.4 mmol) was stirred at 100 8C for the time speci®ed in Table 1. Chloroform (60 ml) was added, and the mixture was washed with NaOH solution (5%, 330 ml). The organic layer was separated and dried over MgSO4.The solvent was removed in vacuo, and the remaining oil was subjected to column chromatography (silica gel; eluent, CHCl3) to give the pure product 3a±l. Received, 5th January 1998; Accepted, 16th February 1998 Paper E/8/00167G References 1 A. R. Katritzky, J. Wang, N. Karodia and J. Li, J. Org. Chem., 1997, 62, 4142. 2 A. R. Katritzky, S. A. Belyakov and S. A. Henderson, J. Org. Chem., 1997, 62, 8215. 3 A. R. Katritzky and J. N. Lam, Heteroatom Chem., 1990, 1, 21. 4 A. R. Katritzky, J. Wu, S. Rachwal and P. J. Steel, Acta Chem. Scand., 1993, 47, 167. 5 A. R. Katritzky and I. V. Shcherbakova, J. Heterocycl. Chem., 1996, 33, 2031. 6 A. R. Katritzky, L. Wrobel, G. P. Savage and M. Deyrup- Drewniak, Aust. J. Chem., 1990, 43, 133. 7 A. R. Katritzky and J. Wu, Synthesis, 1994, 597. 8 E. J. Corey and A. W. Gross, Tetrahedron Lett., 1984, 25, 495. 9 P. Cazeau, F. Duboudin, F. Moulines, O. Babot and J. Dunogues, Tetrahedron, 1987, 43, 2075. 10 H. O. House, L. J. Czuba, M. Gall and H. D. Olmstead, J. Org. Chem., 1969, 34, 2324. J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a800167g

出版商:RSC    

年代:1998

数据来源: RSC