ndian Journal of Chemistry 'ol.40B, October2001, pp. 985-988 The Baylis-Hillman reaction: Rate acceleration in silica gel solid phase medium' Deevi Basavaiah • & Ravi Mallikarjuna Reddy School of Chemistry, University of Hyderabad, Hyderabad-500 046, India Received 24 January 2001 ; accepted 23 May 2001 Remarkable rate acceleration in the Baylis-Hillman reaction of aromatic aldehydes with acrylates, particularly rerrbutyl acrylate, in silica gel solid phase medium has been described. The Baylis-Hillman reaction is an atom economy 1d versatile carbon-carbon bond forming reaction ~tween the a-position of the activated alkenes and trbon electrophiles under the influence of catalytic nount of tertiary amine, particularly 1,4azabicyclo[2.2.2]octane (DABCO), producing densely mctionalized molecules which have been utilized in uious important organic transformations t-s. The ost accepted mechanism of this reaction is described Scheme I, taking the reaction between alkyl :rylate and aldehyde as a model case. However, >plication of this reaction is some what crippled by ; slow reaction rate. Thus, the reaction requires vera) days to several weeks for completion, ~pending upon the reactivity of both activated alkene td electrophile.' ·3 As it is desirable for any synthetic ocess, from both practical and economic point of ew, to be accomplished faster and high yielding, trious methods have been described to accelerate the lylis-Hillman reaction. Thus, the application of high 11 essure, 9· 10 microwave irradiation have been ported to provide significant rate acceleration. Rafel .d Leahy have reported that the reaction is faster at C. 12 Kawamura and Kobayashi reported remarkable celeration in the rate of Baylis-Hillman reaction talyzed by DABCO, using lithium perchlorate as a -catalyst in ether at -25°C-0°C. 13 Recently, Aggarwal and co-workers described that 1thanum triflates accelerate the Baylis-Hillman upling of acrylates with aldehydes catalyzed by 14 !\BC0. ·15 Later Aggarwal has also reported that 3U is far superior catalyst for the Baylis-Hillman 1ction between activated alkenes and aldehydes JViding the adducts at much faster rate than using \BCO or 3-hydroxyquiniclidine. 16 !dicated to Prof. U. R. Ghatak on his 70'h birthday Scheme I Literature survey reveals that rate increase also has been observed due to the presence of hydrogen 17 bonding using methanol as solvent or using 3hydroxyquiniclidine1 8 as a catalyst or terminal 19 hydroxy acrylates as activated alkenes. Increased rates have also been reported when the reaction is 21 carried out in water20 or fluorinated solvents due to hydrophobic and fluorophobic effects respectively. During our investigations on applications of the Baylis-Hillman adducts in various stereoselective transformations, we required these adducts derived from tert-butyl acrylate. Literature survey reveals that the usual Baylis-Hillman reaction of benzaldehyde with tert-butyl acrylate under the catalytic influence of DABCO requires 28 days to provide the desired adduct tert-butyl 3-hydroxy-3-phenyl-2-methylenepropanoate in 65 % yield (93 % yield based on converted aldehyde) .Z2 Literature survey also reveal s that the presence of very small amounts of acetic acid (3 mol%) provide better results, thus Baylis-Hillman reaction of benzaldehyde and 4-bromobenzaldehyde with tert-butyl acrylate under the catalytic influence INDIAN J CHEM . SEC B, OCTOBER 2001 986 OH PhCHO, 28d ~ DABCO(cat.) ~ /COOBu' Ph . . ..~ 65% yield 93% (Based on recovored aldehyde) 0 OH {as"' PhCHO, AcOH(cat.) DABCO(cat.), 21 d ~ /COOBu' TI Ph 77% yield OH ~ ArCHO, AcOH(cat.) DABCO(cat.) , 21d Ar· /COOBu' TI 81 % yield Ar = 4-8rC6 H4 Scheme II of DAB CO (1 5 mol%) in the presence of aceti c acid (3 mol%) requires 21 days to provide the desired adducts, tert-but y l 3-hydroxy-3-phenyl-2-methylenepropanoate and tert-but y l 3-hydroxy-3-(4bromophenyl)-2- methyl enepropanoate in 77% and 8 1% yields respecti vely (Scheme 11)? 3 These are very inconveni entl y slow reactions and hence there is a necessity of finding simple meth ods for carrying out these reactions at faster rates. Accordingly, we envisioned th at appropriate solid phase medium reacti on using silica gel or alumina (both neutral and ac idic) might res ult in accelerati on of the reacti on rate. During our attempts in this di rection we have can·ied out the reacti on between benzaldehyde and tert-butyl acrylate in the presence of I 5 mol% of DABCO under vari ous condi tions and the best results were obtained when the reacti on was carri ed out in silica gel (>200 mesh) solid phase medium thus providing the required product, tenbutyl 3-hydroxy-3-phenyl-2-meth ylenepropanoate in 8 1% isolated yields in 36h time. Encouraged by the remark able rate accelerati on in thi s reacti on we have subjected various aro mati c aldehydes to the Bay li s- AcCHO + J ~ Hillman reaction with tert-buty l acry late in the silica gel solid phase medium to provide the desired adducts in good yields (eq .l , Table 1). With a view to furth er understanding this reaction we have also carried out the reaction of benzaldehyde and p-tolualdehyde with methyl and ethyl acrylates in silica gel solid phase medium in the presence of I 5 mol% DABCO (Table I). These res ults are indeed reasonabl y encourag ing. With a view to have a direct compari son of these solid phase medium reaction results with that of the usual DABCO catalyzed reacti ons, we have also carri ed out parallel ex periments wi th the catalyti c amount of DABCO only (without silica gel) under simi lar conditions and a qui ck compari son has been presented in the Table I. We have also presented the literature results (y ields and reaction times) fo r know n mo lecul es in the Table L In concl usion, we have demonstrated th e application of silica gel as solid phase medium for perfo rming the Bay lis-Hillman reacti on parti cul arl y between tert-butyl acrylate and aromatic aldehydes under the influence of catalyti c amou nt of DA BCO (IS mol%) at increased rates. .OR . DABCO(cat.) , rt • Silica gel(>200 mesh) 60-81 % R =methyl , ethyl, 12h-19d tert-butyl AcxTI /CODA - 1-10 (eq .l ) BASA VAIAH et a/. : THE BAYLI S-HILLMAN REACTION 987 rable 1-Bayli s-Hillman reac ti on between aromatic aldehydes and acrylates in silica gel solid phase medium": A compari so n with usual DABC O catal yzed reactio nsb ::HO COOR R= T ime in hrs/d ays Product" Me Me Bu' Bu' Bu' Bu' Bu' Bu' Bu' Et 12h 48h 36h lOd 12d 16d J8d 6d 19d 14h 124 224 324 enyl neth ylphenyl enyl n ethylphenyl n ethylphenyl :thy Iphenyl sopropy Iph en y I ~ro mo ph e n y l phth - 1-yl enyl 4 5 6 7 g24 9 1024 Yi eldsd(%) Silica ge l+ Only DAB CO DAB CO 78 31 79 21 81 18 66 10 T race 78 62 T race 60 Trace 14 65 T race 63 80 5 Literature results Time in Yi eld days (%) 22 6d 94 25 30d 95 28d 9322.23 7d 83 22 \II reac ti o ns were carri ed o ut o n I 0 mmo le scale o f aldehyde w ith ac rylate ( 15 mmo le), DA BC O ( 1.5 mmo le), and silica ge l (2 .50ig). b) All reactions were carri ed o ut o n 10 mmo le scale o f aldehyde with acrylate ( 15 mmo le) and DABC O ( 1.5 mmole). c) T hese ec ul es (1-3, 10) were obtained as colo rless liquids, and the mo lec ul es (4-9) were obtained as s~lid s . d) Yi elds o f the pure produ cts 10) (based o n aldehyde) a fte r column chro matography (s ilica ge l 10% eth yl acetate in hexanes) followed by crystalli zatio n (ethyl tate:hexanes, I :4) at 0°C or di still atio n. perimental Section All melting points were recorded on a Superfit dia) capillary melting po int apparatu s and are corrected. IR spectra were recorded on JASCO-FTmodel 5300 or Perkin Elmer model 1310 !ctrometer using samples as neat liquids or as KBr 1 13 ttes. H NMR (200 MHz) and C NMR (50 MHz) !Ctra were recorded in CDCI 3 on Bruker-AC-200 ~c trometer usin g TMS as an intern al stand ard . emental an alyses were recorded on Perkin-Elmer OC-CHN analyzer. General Procedure for the Baylis-Hillman action in silica gel solid phase medium. Aldehyde 0 mmole), acrylate ( 15 mmole), and DABCO ( 1.5 mo le, 0.168g), silica gel {(>200 mesh), (2.5075g) } were th oroughly and uni fo rmly mixed and is mixture was left at roo m temperature. Reacti o ns !re monitored by TLC. After appropriate time (see tbl e I), ethyl acetate (I 0 mL) was added and stirred oroughl y and filtered . Th e so lid silica ge l was ashed with ethyl acetate (4x l0 mL). The co mbined gani c layer was dri ed ove r anhyd. Na 2S04 and mcentrated. The crude compo und was purified by ,)umn chromatograph y (s ilica gel, 10% ethyl acetate hexanes) fo ll owed by di still ati on or by ystalli zati o n (eth yl acetate: hex an es, I :4) at 0°C to ·ov ide the pure Bayli s-Hillman alcoho ls (1-10). The >mpounds 1-3, 8, and 10 are known in the literature 1d their spectral (IR, 1H and I o r 13C NMR) data are :ported. Spectral data of these mo lecul es are in ~reement with literature data. 25 tert - Butyl 3-hydroxy-2-methylene-3-( 4-methylhenyl)propanoate 4: Co lo rl ess crystals; yield : 66%; 1 1 m.p. 41-43 °C; IR : 1639, 1714,3414 cm- ; H NMR: 8 1.40 (s, 9H), 2.33 (s, 3H), 2.98 (b, 1H), 5.47 (s, I H), 5.71 (s, 1H), 6.23 (s, lH), 7.14 (d, 2 H, I= 7.6 Hz), 7.24 (d, 2H, I= 7.6 Hz) ; 13 C NMR: 8 2 1.05, 27 .93, 73 .15, 81.40, 124.71 , 126.54, 128.95 , 137.18 , 138 .79, 143.74, 165 .67. An al. Calcd for Ct 5H2o0 3: C, 72.55; H, 8. 12. Found : C, 72.65 ; H, 8.10 %. tert-Butyl 3-hydroxy-2-methylene-3-(2-methylphcnyl)propanoate 5: Co lorl ess crystals; yield: 78%; 1 1 m.p. 54-55 °C ; IR: 1640, 1716, 3350 cm- ; H NMR : 8 1.43 (s, 9H), 2. 33 (s, 3H), 2.90 (b, I H), 5.50 (s, 1H), 5.74 (s, 1H), 6.23 (s, 1H ), 7.13-7 .27 (m, 3H), 7.357.43 (m, 1H) ; 13 C NMR: 8 19. 11 , 27 .97 , 69.52, 8 1.50, 125.05 , 126.14, 126. 26, 127.72, 130.3 8, 135 .70, 139.20, 143.37, 166.07 . An al. Calcd fo r C1 5H2oOf C, 72.55; H, 8.12 . Found : C, 72.31 ; H, 8.16 %. tert-Butyl 3-hydroxy-2-methylene-3-(4-ethylphenyl)propanoate 6 : Colorl ess crys tals; yield : 62%; m.p. 46-48 °C ; IR : 1635,- 1714,3337 cm-1; 1H NMR: 8 1.22 (t, 3 H, I= 7 .2 Hz), 1.40 (s, 9 H), 2.64 (q, 2 H, I = 7.2 Hz), 3.05 (d, lH , I= 5.0 Hz), 5.48 (d, I H, I = 5.0 Hz), 5.72 (s, lH ), 6.24 (s, 1H), 7.1 6 (d, 2 H, I= 7.8 Hz), 7.27 (d, 2 H, I= 7. 8 Hz); 13 C NMR : 8 15.5 1, 28 .00, 28.56, 73.36, 81.51 , 124.77 , 126.65, 127. 83 , 139.09, 143.74, 165 .78. An al. Calcd fo r C1 6H220 3: C, 73.25; H, 8.45 . Found : C, 72 .97 ; H, 8.42 %. tert-Butyl 3-hydroxy-2-methylene-3-(4-isopropylphenyl)propanoate 7: Co lorless crystals; yield: 1 1 60%; m.p. 43-45 °C ; lR: 1635, 171 4, 3325 cm- ; H NMR : 8 1.24 (d, 6H , I= 7.0 Hz), 1.40 (s, 9H ), 2.90 (sept, I H, I= 7.0 Hz), 3.02 (d, I H, I= 5.6 Hz), 5.49 988 INDIAN 1 CHEM. SEC B, OCTOBER 2001 (d, 1H, 1=5.6 Hz), 5.72 (s, 1H), 6.24 (s, 1H), 7.19 (d, 2H, I= 8.0 Hz), 7.28 (d, 2H, 1 = 8.0 Hz); 13C NMR: 8 23.97, 28.00, 33.85, 73.38, 81.51, 124.77, 126.39, 126.64, 139.22, 143.91, 148.41, 165.80. Anal. Calcd for C 17 H24 0 3: C, 73.88; H, 8.75. Found: C, 74.09; H, 8.73 %. tert-Butyl 3-hydroxy-2-methylene-3-(naphth-1yl)propanoate 9: Colorless crystals; yield: 63 %; m.p. 95-98 °C; IR: 1639, 1714, 3412 em·'; 1H NMR: 8 1.42 (s, 9H), 1.91 (b, 1H), 5.51 (s, I H), 6.27 (s, 1H), 6.34 (s, 1H), 7.44-8.09 (m, 7H); 13 C NMR: 8 27.97, 69.38, 81.54, 123.84, 124.41, 125.34, 125 .58, 125.71, 126.15, 128.49, 128.71 , 131.02, 133.85, 137.01 , 143.62, 166.10. Anal. Calcd for C, 8 H2o0 3 : C, 76.03; H, 7.09. Found: C, 75 .85; H, 7.12 %. Acknowledgement We thank DST, New Delhi for funding this project and the UGC, New Delhi for the Special Assistance Program in Organic Chemistry in the School of Chemistry, University of Hyderabad. RMR. thanks CSIR, New Delhi for his research fellowship. References I Drewes S E & Roos G H P, Tetrahedron , 44, 1988, 4653. 2 Basavaiah D, Dharma Rao P & Suguna Hyma R, Tetrahedron , 52, 1996, 8001. 3 Ciganek E, Organic reactions, Vol. 51, Edited by Paquette, L. A. (John Wiley, New York), 1997, p 201-350. 4 lwabuchi Y, Nakatani M, Yokoyama N & Hatakeyama S, 1 Am Chem Soc, 121, 1999, 10219. 5 Sugahara T & Ogasawara K, Synle/1, 1999, 419. 6 Basavaiah D, Krishnamac haryulu M, Suguna Hyma R, Sarma P K S & Kumaragurubaran N, 1 Org Clwn, 64, 1999, 1197. 7 Basavaiah D, Bakthadoss M & Pandiaraju S, Chem Commun, 1998, 1639. 8 Yang K S & Chen K, Organic Lei/, 2, 2000, 729. 9 Hill 1 S & Isaacs N S, Tetrahedron Lell, 27, 1986, 5007. 10 Hill 1 S & Isaacs N S, 1 Chem Res, 1988,330. II Kundu M K, Mukherjee S B, Balu N, Padmakumar R & Bhat S V, Syn/e/1, 1994,444. 12 Rafel S & Leahy 1 W, 1 Org Chem, 62. 1997, 1521. 13 Kawamura M & Kobayas hi S, Tetrahedron Lell, 40, 1999, 1539. 14 Aggarwal V K, Tarver G 1 & McCague R, Chem Commun , 1996,27 13. 15 Aggarwal V K, Mereu A, Tarver G 1 & McCague R, 1 Org Chem, 63, 1998, 7183. 16 Aggarwal V K & Mereu A, Chem Commun, 1999. 23 11. 17 Ameer F, Drewes S E, Freese S & Kaye P T, Synth Commun, 18, 1988, 495 . 18 Drewes S E, Freese S D, Emslie N D & Roos G H P, Synth Commun. 18, 1988, 1565. 19 Basavaiah D & Sarma P K S, Synth Commun, 20, 1990, 1611. 20 Auge J, Lubin N & Lubineau A, Tetrah edron Lei/, 35, 1994. 7947. 21 Vojkovsky T, Abstr Pap Am Chem Soc, 211, 1996, 288. 22 Fort Y, Berthe M C & Caubere P, Tetrahedron, 48, 1992, 6371. 23 Hoffman H M R, Gassner A & Eggert U, Chem Ber, 124, 1991 , 2475. 24 These mo lec ules were earlier prepa red and wel l characterized. Fo r molec ul es I, 3 and 10 see ref. 22. For molecules 3 and 8, see ref. 23 . For molecu le 2, see ref. 25. 25 Foucaud A & Roui lle E, Synth esis, 1990, 787.
© Copyright 2024 Paperzz