TAP CH PHAT TRIEN KH&CN, TAP 11, SO 08 - 2008

NGHIN CU S DNG BENTONITE BNH THUN BIN TNH LM XC TC CHO PHN NG GHP I HECK GIA IODOTOLUENE V STYRENE
Phan Thanh Sn Nam, Vng Quang Tho Trng i hc Bch khoa, HQG -HCM 1. GII THIU Phn ng ghp i xy dng b khung carbon t nhng phn t n gin nh vo cc xc tc kim loi chuyn tip v ang thu ht s quan tm ca cng ng cc nh khoa hc trong sut hn 30 nm qua [1]. Trong , phn ng ghp i Heck gia cc dn xut halogen ca hydrocarbon thm vi cc alkene u mch nh styrene v dn xut ca n c xem l mt trong nhng phn ng quan trng nht, c ng dng rng ri trong ngnh sn xut cc ho cht cao cp, sn xut cc dc phm quan trng cng nh cc vt liu k thut c tnh nng cao [2,3]. Phn ng Heck thng s dng xc tc Pd dng ng th hoc d th, trong xc tc Pd d th ang c quan tm do vn tch v tinh ch sn phm d dng hn, cng nh xc tc d th s c kh nng thu hi v ti s dng tt hn ph hp vi hng i ca ha hc xanh [4]. Ngy nay, ngi ta vn phi s dng cc xc tc phc Pd t tin cho phn ng Heck, v cc nh khoa hc vn ang nghin cu vi mc ch s tm ra mt loi xc tc tt nht cho phn ng ny [5]. Vic s dng bentonite Bnh Thun bin tnh lm xc tc cho cc phn ng tng hp hu c c cc nh khoa hc trong nc nghin cu t nhiu nm qua, c bit l nhm nghin cu ca tc gi Ng Th Thun v cc cng s i hc Quc gia H Ni [6,7]. Cc nghin cu ni trn tp trung vo vic trao i bentonite Bnh Thun vi cc kim loi nh Fe3+, Al3+, Zn2+ lm xc tc acid rn trong cc phn ng alkyl ho hoc ng phn ho, hoc s dng bentonite Bnh Thun lm cht mang cho cc tc nhn oxy ho. Theo hiu bit ca chng ti, mc d phn ng ghp i ni chung v phn ng Heck ni ring ang c cc nh khoa hc trn th gii quan tm nghin cu nhng cc nhm nghin cu Vit Nam vn cha c cc cng b v vn ny. Trong bi bo ny, nhm nghin cu ca chng ti cng b cc kt qu nghin cu v kh nng s dng bentonite Bnh thun trao i vi Pd2+ lm xc tc cho phn ng ghp i Heck gia 4iodotoluene v styrene.

2. THC NGHIM 2.1. iu ch xc tc Bentonite Bnh Thun c s ch v tinh ch theo quy trnh cng b trc y ca nhm nghin cu chng ti [8]. Bentonite tinh ch c hot ho bng dung dch HCl 10% vi t l rn:lng l 1:22 (tnh trn khi lng kh tuyt i), khuy lin tc 70oC trong 6 gi. Hn hp sau em lc, ra bng nc ct cho n ht ion Cl - (kim tra bng dung dch AgNO3), sy kh v nghin mn, thu c bentonite-H+. Bentonite-H+ c tin hnh trao i vi dung dch mui PdCl2 0,016 M (PdCl2 c cung cp bi Cng ty Kanto Chemical Nht Bn) vi t l rn lng l 1:8 (tnh trn khi lng kh tuyt i), khuy lin tc 70oC trong 24 gi. Hn hp sau khi trao i xong c em lc, ra bng nc ct cho n ht ion Cl- (kim tra bng dung dch AgNO3), sy kh v nghin mn, ry qua ry 100 mesh, thu c xc tc bentonite-Pd2+, bo qun trong bnh ht m. 2.2. Xc nh mt s c trng ca xc tc

Science & Technology Development, Vol 11, No.08 - 2008 Mu bentonite-H+ c xc nh ph nhiu x Rnghen ti Vin Du Kh Vit Nam, s dng my Rnghen Siemens ca c trong iu kin ng pht tia bng Cu, bc sng K = 1,5046 , cng ng pht 35 mA, in p 40 KV, gc qut 2 thay i t 3-65o, phm lc Ni. B mt ring ca xc tc bentonite-Pd2+ c xc nh bng phng php hp ph BET theo N2 77 K. Mu c o ti Phng Th nghim Phn tch thuc Vin Cng ngh Ho hc TP. H Ch Minh. Hm lng Pd trong xc tc bentonite-Pd2+ c xc nh bng phng php quang ph hp thu nguyn t (AAS). Mu c o ti Trung tm Dch v Phn tch Th nghim TP. H Ch Minh. 2.3. Kim tra hot tnh xc tc trong phn ng Heck Hot tnh ca xc tc bentonite-Pd2+ c xc nh trong phn ng ghp i Heck gia 4iodotoluene v styrene. Quy trnh phn ng c thc hin da theo cc ti liu cng b trc y [9]. Pha 250 ml dung dch gc ca 4-CH3-C6H4I trong cc dung mi tng ng, c cha mt lng hexadecane C16H34 dng lm ni chun cho phn ng, vi t l mol 4-CH3-C6H4I : C16H34 l 1:1. Mi phn ng thc hin vi 5 ml dung dch hn hp ni trn, tng ng vi 0,12 ml 4-CH3C6H4I. Dung dch phn ng c cho vo bnh cu 2 c c cha sn mt lng xc tc tng ng, v cho thm mt lng base tng ng vi t l mol 4-CH3-C6H4I: base c c nh l 1:3. Sau cho 0,2 ml styrene vo dung dch phn ng, tng ng vi t l mol 4-CH3-C6H4I : styrene c nh l 1:1,5. Hn hp phn ng c nng n nhit thch hp bng bp khuy t gia nhit. Ti thi im ban u v cch mi gi phn ng, dng kim tim ly 0,2 ml mu, ho tan vo 1 ml ether v trch ly vi 1 ml nc ct. Tc cht v sn phm tan trong pha ether v base tan trong pha nc. Pha ether c em i phn tch sc k kh (GC), t tnh chuyn ho ca phn ng theo phng php da trn ni chun. Sn phm ca phn ng cn c kim chng bng phng php sc k kh ghp khi ph (GC-MS) vi iu kin: ct Agilent 19091s, 30 m x 0,25 mm x 0,25 mm x 0,25 m; detector MS, kh mang helium, nhit injector 300oC, nhit detector 300 oC, vn tc kh mang 36 cm/s, chng trnh nhit nh sau: 60oC (1 pht) 5oC/pht o 100 C 10oC/pht o 145 C 25oC/pht o 300 C (3 pht)

3. KT QU V THO LUN Tng t nh cng b trc y ca nhm nghin cu chng ti khi iu ch xc tc bentonite Bnh Thun bin tnh cho phn ng alkyl ho [8], kt qu ph nhiu x Rnghen ca mu bentonite-H+ cho thy bentonite Bnh Thun hot ho bng dung dch HCl 10% cha thnh phn ch yu l montmorillonite v qu trnh hot ha loi b hon ton lng khong calcium. Kt qu phn tnh b mt ring BET cho thy din tch b mt ring ca xc tc bentonite-Pd2+ l 160,36 m2/g. Kt qu phn tch quang ph hp thu nguyn t (AAS) cho thy hm lng Pd c trong xc tc bentonite-Pd2+ l 0,14 mmol/g xc tc. Hot tnh ca xc tc bentonite-Pd2+ c nh gi thng qua phn ng ghp i Heck gia 4-iodotoluene v styrene (Hnh 1). Phn ng c thc hin trong dung mi vi s c mt ca mt base. Sn phm ca phn ng l trans-4-methylstilben (I) v 1-phenyl-1-tolylethylene (ng phn gem-) (II), trong sn phm chnh lun lun l trans-4-methylstilben [4], l sn phm bn nht v c nhit si cao nht. Kt qu nghin cu trc y ca chng ti cho thy sn phm ca phn ng Heck s dng xc tc bentonite bin tnh l ng phn trans-, gem- v vt ca ng phn cis-, c phn bit da trn thi gian lu ca cc cht chun (Sigma-Aldrich) trn sc k [10]. Kt qu ny tng t nh kt qu nghin cu ca nhm nghin cu Varma v cng s

TAP CH PHAT TRIEN KH&CN, TAP 11, SO 08 - 2008 Trng i hc Sam Houston State (Hoa K) trong xc tc Pd c iu ch da trn khong st montmorillonite K10 [11]. Kt qu phn tch sc k kh cho thy t l sn phm (I) : (II) vo khong 7,5:1. Ln lt kho st nh hng ca cc yu t dung mi phn ng, loi base, nhit phn ng, hm lng xc tc ln chuyn ho tng cng ca phn ng.
I + CH3 CH3 CH3 (I) (II) Pd to +

Hnh 1. Phn ng Heck gia iodotoluene v styrene

3.1. nh hng ca dung mi phn ng Phn ng Heck s dng xc tc bentonite Bnh Thun bin tnh c thc hin trong ba loi dung mi khc nhau: dung mi phn cc khng c proton l dimethylformamide (DMF), dung mi phn cc c proton l ru isoamyl (C5H11OH), v dung mi khng phn cc l xylene. Nhit ca phn ng l 120oC, base s dng l triethylamine (Et3N), hm lng xc tc s dng l 0,5 mol% (t l mol gia Pd v 4-iodotoluene). Kt qu nghin cu cho thy phn ng t chuyn ha tng cng cao nht khong 61,3% trong dung mi DMF sau 6 gi phn ng, trong khi cc dung mi C5H11OH v xylene ch cho chuyn ha hu nh khng ng k, di 2% trong cng thi gian phn ng (Hnh 2).
80 DMF chuyn ho (%) 60 40 20 0 0 1 2 3 4 Thi gian (h) 5 6 isoamyl xylene

Hnh 2. nh hng ca dung mi ln chuyn ho ca phn ng (nhit 120oC, 0,5 mol% xc tc Pd, base l triethylamine)

T cho thy DMF l dung mi thch hp cho phn ng Heck s dng xc tc bentonite Bnh Thun bin tnh. C nhiu quan im cho rng cc dung mi phn cc khng c proton nh DMF c kh nng gp phn h tr cho qu trnh kh Pd (II) v Pd (0), v Pd (0) mi l xc tc thc s cho phn ng Heck [4,5]. Qu trnh kh Pd (II) v Pd (0) cng thun li th cng thc y cho phn ng Heck xy ra. Cc dung mi khng phn cc nh xylene hoc phn cc c proton nh ru isoamyl do khng giu in t nn khng h tr cho qu trnh kh Pd (II) v Pd (0). Tuy nhin, c ch ca qu trnh ny vn cha c gii thch r rng trong cc cng trnh khoa hc cng b. 3.2. nh hng ca loi base c s dng

Science & Technology Development, Vol 11, No.08 - 2008

Hnh 3. nh hng ca base ln chuyn ho ca phn ng (nhit 120oC, dung mi DMF, 0,5 mol% xc tc Pd)

Phn ng Heck gia 4-iodotoluene v styrene sinh ra sn phm ph l HI, v acid ny s phn ng vi xc tc Pd. V vy, cn phi s dng mt base trung ha lng acid ny, ti sinh li xc tc dng Pd (0) [2]. kho st nh hng ca cc base s dng, phn ng c thc hin trong dung mi DMF nhit 120oC vi hm lng xc tc l 0,5 mol%. Cc nghin cu trc y cho thy c th s dng nhiu loi base khc nhau cho phn ng Heck, c th l base hu c hay base v c, ty thuc vo loi xc tc cng nh iu kin phn ng [5]. Cc base c s dng cho phn ng gia 4-iodotoluene v styrene trong nghin cu ny ln lt l triethyl amine (Et3N), Na2CO3, v CH3COONa. Kt qu nghin cu (Hnh 3) cho thy trong giai on u, phn ng s dng base dng ha tan l Et3N cng nh CH3COONa cho chuyn ha cao hn so vi trng hp s dng base kh tan l Na2CO3. Do xc tc Pd s dng dng rn, lng HI sinh ra vn cn kt hp vi cc trung tm Pd dng rn ny. V vy, qu trnh trung ha HI ph thuc vo qu trnh khuch tn base vo bentonite. Trong giai on u, base Na2CO3 dng bt rn c tan trong DMF thp hn so vi Et3N v CH3COONa nn phn ng tng ng cho chuyn ha thp hn. Sau khong 4 gi phn ng, lng Na2CO3 tan trong DMF ln, chuyn ha ca phn ng tng ln v t 61,3% sau 6 gi, cao hn so vi phn ng s dng Et3N (47,9%) v CH3COONa (44%). Nh vy trong cc base s dng, Na2CO3 thch hp cho phn ng Heck s dng xc tc bentonite bin tnh. 3.3. nh hng ca nhit Trong nhiu nghin cu, phn ng Heck vi xc tc Pd rn c thc hin trong mt khong nhit kh rng, khong t 80oC n 150oC, ty thuc vo loi xc tc v tc nhn phn ng [4]. Nhit cao gip cho phn ng xy ra d dng hn. Tuy nhin DMF d b phn hu mt phn nhit gn nhit si (153oC) nn trong nghin cu ny, cc phn ng c kho st cc nhit ln lt l 120oC, 110oC v 100oC. Cc phn ng s dng hm lng xc tc l 0,5 mol% v base l Na2CO3 trong dung mi DMF. Kt qu nghin cu (Hnh 4) cho thy sau 6 gi phn ng, phn ng thc hin nhit 120oC, 110oC v 100oC c chuyn ha ln lt l 61,3%, 37,7% v 6,8%.

TAP CH PHAT TRIEN KH&CN, TAP 11, SO 08 - 2008

80
chuyn ho (%)

60 40 20 0 0 1

100 110 120

Thi gian (h)

Hnh 4. nh hng ca nhit ln chuyn ho ca phn ng (dung mi DMF, base l Na2CO3, 0,5 mol% xc tc Pd)

3.4. nh hng ca hm lng xc tc Phn ng Heck gia 4-iodotoluene v styrene c kho st vi cc hm lng xc tc khc nhau: 0,7 mol%, 0,5 mol% v 0,3 mol%. Cc phn ng c thc hin trong dung mi DMF, nhit 120oC vi base l Na2CO3. Kt qu th nghim (hnh 5) cho thy sau 6 gi phn ng, chuyn ha t c ln lt l 76% ( hm lng xc tc 0,7 mol%), 61,3% ( hm lng xc tc 0,5 mol%) v 20,7% ( hm lng xc tc 0,3 mol%). Kt qu ny tng t nh nhiu nghin cu khc, trong tc phn ng tng theo hm lng xc tc s dng. Tuy nhin do Pd l mt kim loi qu v xc tc c chi ph cao, trong thc t ty iu kin c th m chn lng xc tc thch hp. Kt qu nghin cu cn cho thy xc tc bentonite Bnh Thun bin tnh c hiu qu trong phn ng Heck hm lng Pd tng i thp.
80
chuyn ho (%)

0.5% 0.3% 0.70%

60 40 20 0 0 1 2 3 4 5 6
Thi gian (h)

Hnh 5. nh hng ca hm lng xc tc ln chuyn ho ca phn ng (dung mi DMF, nhit 120oC, base l Na 2CO3)

3.5. Kh nng thu hi v ti s dng xc tc Mt vn cn quan tm ca cc phn ng s dng xc tc rn l kh nng thu hi v ti s dng xc tc. Sau khi cc phn ng kt thc, lng xc tc bentonite-Pd2+c lc ra nhiu ln vi cc dung mi nh toluene, DMF, nc, ethanol loi b cc tc cht hp ph vt l trn b mt xc tc. Sau xc tc thu hi c sy kh v s dng li cho phn ng mi gia 4iodotoluene v styrene. iu kin phn ng tng t nh phn ng vi xc tc mi: dung mi s dng l DMF, base s dng l Na2CO3, nhit phn ng l 120oC, khi lng xc tc thu hi v lng tc cht phn ng tng t nh trng hp phn ng s dng xc tc mi. Kt qu nghin cu cho thy sau 6 h, phn ng s dng xc tc thu hi cho chuyn ha 41,1% (phn ng s

Science & Technology Development, Vol 11, No.08 - 2008 dng xc tc mi trong cng iu kin cho chuyn ha 61,3%). Nh vy mc d hot tnh gim, xc tc bentonite Bnh Thun bin tnh vn c kh nng thu hi v ti s dng. Tuy nhin, vn ny cn c tip tc cc nghin cu tip theo. 3.6. Thc hin phn ng trong iu kin c s h tr ca vi sng Vic thc hin cc phn ng tng hp hu c trong iu kin c s h tr ca vi sng (microwave) v ang thu ht s quan tm ca cc nh ha hc. Cc phn ng hu c thc hin trong l vi sng c thi gian phn ng ngn hn nhiu so vi cc phng php gia nhit thng thng [12]. Ngoi ra, cc nghin cu trc y cho thy vi s c mt ca vi sng, chuyn ha ca phn ng c tng mt cch ng k [13]. Trong nghin cu ny, phn ng Heck gia 4-iodotoluene v styrene c thc hin trong l vi sng gia dng Whirlpool, Model AVM541/WP/WH c th iu chnh c cng sut v thi gian. Phn ng c thc hin cng sut 800 W trong bnh cu c gn sinh hn hon lu nc t trong lng l vi sng. iu kin phn ng tng t nh trng hp gia nhit thng thng: dung mi s dng l DMF, base s dng l Na2CO3, hm lng xc tc bentonite Bnh Thun bin tnh s dng l 0,5 mol% Pd.
100
chuyn ho (%)

80 60 40 20 0 0 15 30 45 60
Thi gian (pht)

Hnh 6. chuyn ha phn ng Heck trong iu kin c h tr ca vi sng (dung mi DMF, base l Na2CO3, 0,5 mol% xc tc Pd, cng sut 800 W)

Kt qu nghin cu (Hnh 6) cho thy tc phn ng tng mt cch ng k so vi trng hp gia nhit thng thng. chuyn ha ca phn ng t n 97% ch sau 1 gi phn ng. Trong khi , phn ng trong iu kin gia nhit thng thng ch cho chuyn ha 61,3% sau 6 gi phn ng vi cng mt hm lng xc tc (0,5 mol%), cng dung mi (DMF) v cng base (Na2CO3). iu ny c th c gii thch da trn tc dng ca vi sng trong iu kin s dng dung mi phn cc nh DMF. Cn lu cc phn t phn cc chu nh hng ca vi sng nhiu hn. Cp nhit bng vi sng din ra trong lng dung dch v ng nht hn, gip cho qu trnh phn ng cng nh cc qu trnh khuch tn, hp ph v gii hp ph trn b mt xc tc din ra tt hn [14]. 4. KT LUN Tm li, nhm nghin cu chng ti iu ch xc tc bentonite Bnh thun bin tnh theo phng php trao i cation vi dung dch PdCl2, vi hm lng Pd c trong xc tc l 0,14 mmol/g xc tc. Xc tc c b mt ring BET l 160,36 m2/g. Xc tc Pd iu ch c c hot tnh cao trong phn ng ghp i Heck gia 4-iodotoluene v styrene, t c chuyn ho 61,3% (trong t l sn phm trans-4-methylstilben: 1-phenyl-1-tolylethylene vo khong 7,5:1) sau 6 gi phn ng vi iu kin: dung mi phn ng l DMF, hm lng xc tc l 0,5 mol%, nhit phn ng l 120oC, base s dng l Na2CO3. Kt qu nghin cu cn cho thy xc tc iu ch c c kh nng thu hi v ti s dng trong phn ng Heck. Khi thc hin

TAP CH PHAT TRIEN KH&CN, TAP 11, SO 08 - 2008 phn ng trong iu kin c s h tr ca vi sng, tc phn ng tng ln ng k, chuyn ha t n 97% ch trong 1 gi phn ng, vi hm lng xc tc 0,5 mol%. Mc d y mi ch l nhng kt qu bc u nhng m ra trin vng s dng bentonite Bnh Thun bin tnh lm xc tc cho cc phn ng ghp i xy dng b khung carbon l cc phn ng quan trng ang c cc nh khoa hc trn th gii quan tm nhng vn cha c nghin cu nhiu Vit Nam - v hng nghin cu ny cn c tip tc.

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TI LIU THAM KHO [1]. K. C. Nicolaou, Paul G. Bulger, and David Sarlah, Palladium-catalyzed cross-coupling reactions in total synthesis, Angewandte Chemie International Edition, 44, 4442-4489 (2005). [2]. David H. Brown, Evaluation of kilogram-scale Sonogashira, Suzuki, and Heck coupling routes to oncology candidate CP-724,714, Organic Process Chemical Research & Development, 9, 440-450 (2005). [3]. Lutz F. Tietze, Hiriyakkanavar IIa, and Hubertus P. Bell, Enantioselective palladiumcatalyzed transformations, Chemical Reviews, 104, 3453-3516 (2004). [4]. Irina P. Beletskaya, and Andrei V. Cheprakov, The Heck reaction as a sharpening stone of palladium catalysis, Chemical Reviews, 100, 3009-3066 (2000). [5]. Nam T. S. Phan, Matthew Van Der Sluys, and Christopher W. Jones, On the nature of the active species in palladium catalyzed Mizoroki-Heck and Suzuki-Miyaura couplings homogeneous or heterogeneous catalysis, a critical review, Advanced Synthesis & Catalysis, 348, 609-679 (2006). [6]. Nguyn c Chu, Trng Minh Lng, Ng Th Thun, Phn ng ankyl ha toluen bng isopropyl bromua trn xc tc bentonit Thun Hi bin tnh, Tp ch Ha hc, 35, 70-74 (1997). [7]. Ng Th Thun, Hoa Hu Thu, Nguyn Vn Bnh, Trn Th Thu Nga, Tng hp v c trng ca t st Thun Hi c chng bng cc polioxocation kim loi, Tp ch Ha hc, 35, 29-33 (1997). [8]. Trn Th Vit Hoa, Trn Hu Hi, Phan Thanh Sn Nam, Nghin cu phn ng alkyl ha toluene trn xc tc bentonite bin tnh, Tp ch Pht trin Khoa hc & Cng ngh, 3, 6471 (2000). [9]. Nam T. S. Phan, David H. Brown, Harry Adams, Sharon E. Spey, and Peter Styring, Solid-supported cross-coupling catalysts derived from homogeneous nickel and palladium coordination complexes, Dalton Transactions, 1348-1357 (2004). [10]. Phan Thanh Sn Nam, Bi Th Hng Hng, ng c Tu, Trn Th Thanh Tho, Nghin cu s dng bentonite Bnh Thun bin tnh lm xc tc cho phn ng Heck ca iodobenzene v styrene, Hi ngh Xc tc & Hp ph ton quc ln th IV, thng 8 nm 2007. [11]. Rajender S. Varma, Kannan P. Naicker, Per J. Liesen, Palladium chloride and tetraphenylphosphonium bromide intercalated clay as a new catalyst for the Heck reaction, Tetrahedron Letters, 40, 2075-2078 (1999). [12]. C. Oliver Cappe, Controlled microwave heating in modern oragnic synthesis, Angewandte Chemie International Edition, 43, 6250-6284 (2004). [13]. Nicholas E. Leadbeater, Fast, easy, clean chemistry by using water as a solvent and microwave heating: the Suzuki coupling as an illustration, Chemical Communications, 2881-2902 (2005). [14]. Antonio de la Hoz, Angel Diaz-Ortiz, Andres Moreno, Microwaves in organic synthesis: thermal and non-thermal microwave effects, Chemical Society Reviews, 34, 164-178 (2005).