Microwave-activated Coupling Reaction on Polyethylene Glycol

Chinese Chemical Letters Vol. 13, No.1, pp 1 - 2, 20021http://www.imm.ac.cn/journalcc.htmlMicrowave- activated Coupling Reaction on Polyethylene GlycolMin XIA, Yan Guang WANG*Department of Chemistry, Zhejiang University, Hangzhou 310027Abstract: The two-step Sonogashira coupling reaction took place rapidly under microwave :activation conditions. PEG bound substrates acted as PTC and polymer support as well. Itsyields are 80~90% and the products are in high purity.Keywords: Microwave activated, coupling and cleavage, PEG liquid- phase.The liquid-phase synthesis of small organic compounds on soluble polymers has been thepreferable strategy. It has both the advantages of liquid-phase and solid-phase methods'.One particular attractive field is the coupling reaction with the solvent-free phase-transfer catalysis (PTC) in microwave activation'. Recently, it has been reported thatPEG bound substrates could play the role of PTC in some reactions', here we reportedthe first example of the microwave activated Sonogashira reaction under the solvent-freecondition using PEG 4000 as the PTC and polymer support (Scheme 1).Scheme 110%Cul, 5%Pd(PPh 3)XCl 2DCC 1 DMAP (cat)=-R，K2CO3HOOC- ICH2Cl2 3fc<0-1M.W.460w,1.5min.PEG- o'overnight, 98.75vieldi) IMol/L NaOH (aq. 10mL)M.W.600w. lmin.一HOC-O>-=--Ri) 5Mol/L HCI (aq. 3mL)Table 1 (entries 1, 3) showed that the microwave method could shorten thecoupling reaction time dramatically (from 3 h to 1.5 min), the yields of products wereapproximately equal though. For the entries 3 and 2 (Table 1), one could find that theyields of product were also improved significantly, when PEG 4000 supported 4-iodobenzoic acid was used as the substrate. In the coupling reaction, PEG 4000 actedas the solid-liquid PTC and polymeric support as well. Our study indicated thatmicrowave radiation was also efficiently for the cleavage of products from PEG support.The cleavage proceeded very fast just in one minute, while it took 5 hours at 50°C for thetraditional heating method. To our knowledge, there is no report on the cleavage of* E-mail: orgwyg @ css.zju.edu.cn中國煤化工MHCNMH G.Min XIA et al.products from PEG support by microwave activated method.Table 1 Microwave activated coupling and cleavage reactions on PEG 4000 support°EntYield Purityalkynes'H-NMR (500MHz, CDCI,)' δ pm(%)(%)"HC = CCHOH91dHC= CCHOH681.80(br, lH, OH), 4.40 (s, 2H, CH2)HC= CCH2OH893.90 7.54 (d, 2H, J=8.3Hz ArH,8.067.47(m, 2H, PhH), 7.57(m, 3H, PhH)Hq=CPh95.457.64(d, 2H, J=8.5Hz, ArH), 8.1 l(d, 2H, J=8.5Hz, ArH)0.96 (1, 3H, J=7.2Hz, CH), 1.49 (m, 2H, CH2)HE=CCH9-1001.61 (m, 2H, CH), 2.45 (t, 2H, J=7.2Hz, CH)7.49 (d, 2H, J=8.5Hz, ArH), 8.03 (d, 2H, J=8.5Hz, ArH)c=CIH0.98(s, 3H, 130 CH)0.88~2.41(m, 24H, OH and bond-H), 5.85 (s,norethindron7.48(d, 2H, J=8.5Hz. ArH), 8.04 (d, 2H, J=8.5Hz, ArH)a. the coupling and cleavage reactions were carried out under microwave heating withoutadditional solvent; b. based on the original loading capacity of PEG 4000 with 0.5 mmol/g;c. based on the analysis of GC; d. the coupling with 4-iodobenzoic acid was carried out inCH.CN under traditional heating at 40°C for 3 hours; e. the coupling with 4 iodobenzoic acidwas carried out on silica gel under microwave heating; f. The proton signal of COOH could notbe checked;EkecHg. norethindron =ReferencesP. Wentworth, K. D. Janda, Chem. Commun, 1999, 1917.S. Deshayes, M. Liagre, A. Loupy, J. L. Luche, A. Petit, Tetrahedron,1999 .55. 10851.3. C. G. Blettner, W. A. Konig, W. Stenzel, T. Schotten,J. Org. Chem., 1999, 64, 3885.Received 20 February, 2001Revised 18 October, 2001中國煤化工MHCNMH G.