A kinetic study on the reductive opening of the diphenylmethylene acetal in methyl 2,3-O-diphenylmethylene-[alpha]-l-rhamnopyranoside

Accep ed Manusc ip A kine ic s udy on he educ i e opening o me hyl 2,3-O-diphenylme hylene- α-L- hamnopy anoside Dezső Szik a, A ila Mándi, Anikó Bo bás, Is án P. Nagy, Is án Komá omi, A ila Kiss-Szikszai, Mihály He czeg, Sándo An us PII: S0008-6215(11)00232-1 DOI: 10.1016/j.ca es.2011.04.041 Re e ence: CAR 5773 To appea in: Ca bohyd a e Resea ch Recei ed Da e: 31 Janua y 2011 Re ised Da e: 18 Ap il 2011 Accep ed Da e: 27 Ap il 2011 Please ci e his a icle as: Szik a, D., Mándi, A., Bo bás, A., Nagy, I.P., Komá omi, I., Kiss-Szikszai, A., He czeg, M., An us, S., A kine ic s udy on he educ i e opening o me hyl 2,3-O-diphenylme hylene-α-L- hamnopy anoside, Ca bohyd a e Resea ch (2011), doi: 10.1016/j.ca es.2011.04.041 This is a PDF ile o an unedi ed manusc ip ha has been accep ed o publica ion. As a se ice o ou cus ome s we a e p o iding his ea ly e sion o he manusc ip . The manusc ip will unde go copyedi ing, ypese ing, and e iew o he esul ing p oo be o e i is published in i s inal o m. Please no e ha du ing he p oduc ion p ocess e o s may be disco e ed which could a ec he con en , and all legal disclaime s ha apply o he jou nal pe ain. A kine ic s udy on he educ i e opening o me hyl 2,3-O-diphenylme hylene--L- hamnopy anoside Dezs Szik aa, A ila Mándib,c,*, Anikó Bo básb, Is án P. Nagya, Is án Komá omid, A ila Kiss- Szikszaic, Mihály He czegb, Sándo An usb,c a Depa men o Physical Chemis y, Uni e si y o Deb ecen, H-4032, Deb ecen, Hunga y b Resea ch G oup o Ca bohyd a es o he Hunga ian Academy o Sciences, H-4032, Deb ecen, Hunga y c Depa men o O ganic Chemis y, Uni e si y o Deb ecen, H-4032, Deb ecen, Hunga y d Th ombosis, Haemos asis and Vascula Biology Resea ch G oup o he Hunga ian Academy o Sciences, Uni e si y o Deb ecen, H-4032, Deb ecen, Hunga y Dedica ed o P o esso And ás Lip ák on he occasion o his 75 h bi hday Abs ac Reduc i e opening o me hyl 2,3-O-diphenylme hylene--L- hamnopy anoside has been in es iga ed by kine ic s udies, and he esul s ha e been compa ed o hose ecen ly ob ained by quan um chemical calcula ions. In con as o he p e ious heo e ical calcula ions which ela ed only o he p esumably a e limi ing s ep o he educ i e opening, he eac ion sys em among LiAlH4, AlCl3 and he i le compound consis s o a leas ou simul aneous eac ions. Ne e heless, easonable ag eemen can be ound be ween he ac i a ion Gibbs ee ene gy ob ained om kine ic measu emen s and he heo e ically calcula ed ones in spi e o he expe imen al e o s and he app oxima e na u e o heo e ical calcula ions. Keywo ds Diphenylme hylene ace al Reduc i e opening Chlo oalane Kine ics Co esponding au ho . Tel.: +36 52 512 900/22257; ax: +36 52 512 900/22342. E-mail add ess: [email p o ec ed] (A. Mándi). Reduc i e opening o cyclic ace als is e y impo an in syn he ic ca bohyd a e chemis y, acili a ing selec i e p o ec ion o polyol sys ems. Good examples a e he 4,6-O-benzylidene ace als o hexopy anosides,1,2 which can be opened selec i ely unde speci ic condi ions om bo h sides yielding 4-O- o 6-O- e he s.3,4 Reagen s applied o educ i e opening usually consis o an elec ophile (a Lewis o a p o ic acid) and a hyd ide dono . Mix u es o li hium aluminium hyd ide (LAH) and AlCl35 a e widely used o his pu pose, since in an equilib ium eac ion a ious alanes can o m, depending on he a io o LAH and AlCl3, di e ing in hei acidi y and hyd ide-dona ing abili y.6 Ve y ew kine ic expe imen s7,8 and heo e ical wo k9 can be ound in he li e a u e, howe e , o he ing opening o cyclic ace al de i a i es, and hese pape s deal mainly wi h benzylidene ace als and bo ane eagen s. Compa ing o he 4,6-O-benzylidene ace als, pa ial hyd ogenolysis o 2,3-O-diphenylme hylene ace als equi es milde condi ions. 10 Thus educ i e opening o me hyl 2,3-O-diphenylme hylene--L- hamnopy anoside de i a i es was s udied by Hajkó e al. applying LAH and AlCl3 in a 1:1 a io (i.e. chlo oalane) in E 2O/CH2Cl2 1:1. 11 While a he 4-unsubs i u ed de i a i e (1) only he 2-O- diphenylme hyl p oduc was o med, a he 4-OMe o he 4-deoxy cases he eac ion esul ed in a mix u e o 2-O- and 3-O-benzyl e he s, whe e he la e ones we e he majo p oduc s. In he 4- unsubs i u ed case a schema ic eac ion mechanism was p oposed in which i s a 4-O-chlo oalane de i a i e (2) o ms, ollowed by he opening o he dioxolane ing, and inally 3 is hyd olyzed by addi ion o wa e (Scheme 1). Scheme 1. P e ious assump ion o he mechanism o he educ i e opening o 111 F om he quick H2 o ma ion a he ini ial phase o he eac ion he conclusion can be d awn ha 12 eac ion s ep is subs an ially as e han he 23 one, he e o e he 23 ans o ma ion can be ega ded as he a e limi ing s ep. Recen ly, a heo e ical s udy has been p esen ed on he p esumed (23) a e limi ing s ep o he educ i e opening eac ion shown on Scheme 1.12 Based on he quan um chemical calcula ions, a modi ied eac ion mechanism was p oposed o he dioxolane ing opening. I was ound ha he aluminium spon aneously coo dina es o he O3 a om o ming a s ong, almos ully de eloped single bond (a), which leads o weakening o he O3-Cace alic bond. The e ollows a single s ep eac ion which is, howe e , a he asynch onous. Fi s he C-O bond p ac ically anishes (b), and only hen begins he C-H bond o ma ion (c). Ze o poin co ec ed ac i a ion ene gies we e ound o be a ound 125-130 kJ/mol wi h DFT me hods, consis en ly, while HF, MP2 and ONIOM calcula ions esul ed in somewha highe ansi ion s a e ene gies. In o de o u he suppo he eac ion mechanism p oposed ea lie ,12 we ha e pe o med kine ic measu emen s o de e mine he ac i a ion Gibbs ee ene gy o he eac ion expe imen ally. Me hyl 2,3- O-diphenylme hylene--L- hamnopy anoside (1)13,14 was p epa ed om me hyl -L- hamnopy anoside (5) and eshly p epa ed benzophenone dime hyl ace al15 in he p esence o (±)10-campho sul onic acid in MeCN (Scheme 2). Me hyl 2-O-diphenylme hyl--L- hamnopy anoside (4) was syn hesized acco ding o he li e a u e13 wi h LAH/AlCl3 1:1 in E 2O/CH2Cl2 1:1 o use as a s anda d o he HPLC measu emen s. Scheme 2. P epa a ion o 1 wi h ansace aliza ion Fo each (14) eac ion in he kine ic expe imen s we used me hyl 2,3-O-diphenylme hylene-α-L- hamnopy anoside (1), 2 equi . LAH and 2 eq . AlCl3, and he eac ions we e ca ied ou a 10, 15, 20 and 25 °C. LAH was added o he suga solu ion, and a e 1 min he eac ion was s a ed wi h he addi ion o AlCl3 (in o de o exclude he impac o he i s as s ep, i.e. he LAH + ee OH eac ion) (Scheme 3). Samples aken a ce ain imes we e analyzed by HPLC. Scheme 3. Fo ma ion o alkoxy-aluminium hyd ide 1a and he chlo oalane de i a i e 2 in wo s eps caused by he subsequen addi ion o LAH and AlCl3 Based on he p e ious assump ions11 and he heo e ical esul s12 he a e de e mining s ep o he eac ion should ollow i s o de kine ics. Howe e , ou kine ic da a con ain conside able expe imen al e o s, which can mainly a ise om wo ac o s. The i s one is one o he side eac ions, namely he hyd olysis o he ace al ing, since i seems o be e y sensi i e o he LAH/AlCl3 a io which is also a ec ed by a e y ew amoun o wa e may be p esen in he sys em. The second one is he a io o E 2O and CH2Cl2. E en a sligh change o his a io su p isingly seems o al e he a e o LAH-AlCl3 induced educ i e opening eac ions in a signi ican manne .16 Fu he e o s can a ise i.a. om he ela i ely ci cui ous simple p epa a ion p ocess o he HPLC measu emen s. As a consequence o hese ac s he o de o he eac ion could no be de e mined wi h high ce ain y. Ne e heless, he expe imen al da a do no con adic he i s o de kine ics. Acco dingly, a e cons an s o he consump ion o 1 o o ming 4 we e de e mined supposing i s o de kine ics. An example can be seen on Figu e 1. P ima y kine ic da a a e lis ed in Table S1 in he Supplemen a y da a. Figu e 1. Ra e cons an de e mina ion o en y 1 a 10 °C (see Table S1) H, S and G alues ha e been de e mined om hese a e cons an s using he Ey ing-Polányi equa ion (Figu e 2).17,18,19 Ac i a ion Gibbs ee ene gy was ound o be 94.09 kJ/mol. Figu e 2. Tempe a u e dependence o he a e cons an s. H = 64.47 kJ/mol, S = -99.32 J/molK, G = 94.09 kJ/mol a 298.15 K In his expe imen , howe e , he eac ion s eps om he ull eac ion can no be sepa a ed, i.e. i includes he eac ion o alkoxy-aluminium hyd ide (1a) wi h AlCl3 (Scheme 3), he mul iple equilib ium eac ion be ween he excess o LAH and AlCl3, he p esumable a e limi ing 23 eac ion i sel and he hyd olysis o he ace al ing esul ing in 5. Wi h o he wo ds, no only he o ma ion o 2, bu also he side eac ions a e included in he eac ion a e calcula ed om he expe imen s. Ne e heless, he ~100 kJ/mol seems o be he uppe limi o he ac i a ion ee ene gy o he a e de e mining s ep. Compa ing he heo e ically12 and he expe imen ally de e mined ac i a ion pa ame e s, i should be no ed, ha by calcula ions he ac i a ion ene gies co ec ed by ze o poin ib a ional ene gy (ZPVE) we e calcula ed while some kind o o e all ac i a ion ee ene gy was ob ained om he expe imen s. Accep ing he calcula ed ‘o e all’ expe imen al ac i a ion ee ene gy as an ac i a ion (Gibbs) ee ene gy o he eac ion we modeled (e en hough his alue is su e ing om expe imen al e o s) i is s ill subs an ially lowe han any o he p e iously compu ed ze o poin ZPVE co ec ed ac i a ion ene gies.12 I should be no ed, ha compa ison o he calcula ed ZPVE-co ec ed ene gy di e ences (as ac i a ion ene gy) o he ac i a ion ee ene gy is heo e ically inco ec . Howe e , a gas phase model, since he eac ion mechanism was p edic ed o be an in e molecula bond ea angemen nei he subs an ial en opy e ec no subs an ial olume changes a e expec ed and he calcula ed ZPVE- co ec ed ene gy di e ences should be close o he heo e ical ee ene gy di e ences as i was poin ed ou in ou p e ious pape .12 I is ue e en hough he ha monic app oxima ion o he low equency ib a ions can cause la ge unce ain y in he calcula ed ee ene gy, which can be an addi ional sou ce o di e ences be ween he heo e ical and expe imen al alues. Ne e heless, one o he main easons o he disc epancy men ioned abo e p obably esides in he ac ha no sol en molecules we e included in he heo e ical calcula ions. In sol en phase he pola sol en molecules wi h non-bonding elec on pai s can sol a e mo e e ec i ely he ansi ion s a e han he eac an due o he inc eased ha d cha ac e o aluminium a ansi ion s a e geome y compa ed o he eac an geome y. (In he la e case he hyd ide anion is pa ially le he aluminium.) This mo e p e alen sol a ion e ec esul s in bo h dec eased ac i a ion ene gy and loss o en opy (due o he mo e o de ed solu e-sol en in e ac ion) a ansi ion s a e compa ed o he hypo he ical gas phase eac ion. Ano he impo an eason can be ha he p e iously calcula ed a e limi ing eac ion is s ongly asynch onous, since he C-O bond b eaking p ecedes he C-H bond o ma ion and he ansi ion s a e co esponds dominan ly o a hyd ide anion ans e . Fo such sys ems he con ibu ion o unneling e ec is usually non negligible.20 In conclusion, eac ion kine ics s udies on he educ i e opening o me hyl 2,3-O-diphenylme hylene-- L- hamnopy anoside can be sa is ac o ily ea u ed by a i s o de kine ics model which is in a good acco dance wi h he heo e ical eac ion mechanism published ecen ly.12 The mode a e disc epancy be ween he published heo e ical and he expe imen al ac i a ion Gibbs ee ene gy as well as en opy alues p esen ed he e can be a ionalized based on he assump ion o di ec in e ac ion be ween he solu e and sol en molecules (wi h non-bonding elec on pai s) a he ansi ion s a e. 1. Expe imen al 1.1. Gene al Me hods Op ical o a ions we e measu ed a oom empe a u e wi h a Pe kin-Elme 241 au oma ic pola ime e . Mel ing poin s we e de e mined on a Ko le ho -s age appa a us and a e unco ec ed. TLC was pe o med on Kieselgel 60 F254 (Me ck) wi h de ec ion by 5% sul u ic acid in e hanol. Column ch oma og aphy was pe o med on Silica Gel 60 (Me ck 0.062–0.200 mm). The o ganic solu ions we e d ied o e MgSO4 and concen a ed in acuum. The 1H (400.13 and 500.13 MHz) and 13C NMR (100.61 and 125.76 MHz) spec a we e eco ded wi h B uke DRX-400 and B uke DRX-500 spec ome e s o solu ions in CDCl3. In e nal e e ences: TMS (0.00 ppm o 1H), CDCl3 (77.00 ppm o 13C). HPLC sepa a ion condi ions: Wa e s Symme y C18 column 3.5 µm 4.6 x 150 mm, me hanol- wa e 80:20 eluen , low a e: 0.6 ml/min, de ec ion: 220 nm. 1.2. Kine ic de ails Fo each (14) eac ion in he kine ic expe imen s we used 200 mg me hyl 2,3-O-diphenylme hylene- α-L- hamnopy anoside (1), 44 mg (2 equi .) LAH, 156 mg (2 eq .) AlCl3, 20 cm3 E 2O and 20 cm3 CH2Cl2. Reac ions we e ca ied ou in a double-walled eac ion essel a 10, 15, 20 and 25 °C unde A a mosphe e. Be o e s a ing he eac ion 2 cm3 sample was aken om he suga solu ion. LAH was added and a e 1 min he eac ion was s a ed wi h he addi ion o AlCl3 (in o de o exclude he impac o he i s as s ep, i.e. he LAH + ee OH eac ion). Fu he samples we e aken a 2, 5, 10, 20, 30, 40 and 60 minu es. Since he high ola ili y o he sol en s used would esul in a poo ep oducible sample olume, hey we e co ec ed by he mass o each sample. The 2-2 cm3 samples aken a ce ain imes we e quenched wi h a mix u e o me hanol and wa e , and he eac ion sol en s we e e apo a ed by he aid o A . Volumes we e illed up o 10 cm3 wi h me hanol-wa e 80:20, il e ed wi h 0.45 µm sy inge il e and analyzed by HPLC. Acknowledgemen s This wo k was inancially suppo ed by he Hunga ian Scien i ic Resea ch Fund (OTKA K-62802) and he TÁMOP 4.2.1./B-09/1/KONV-2010-0007 p ojec . The p ojec is co- inanced by he Eu opean Union and he Eu opean Social Fund. Supplemen a y da a Supplemen a y da a associa ed wi h his a icle can be ound, in he online e sion, a doi: