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TONG HdP MOT SO O A N XUAT HYDRAZON CUA AXIT GLUCONIC NGUYEN MINH THAO, N G U Y I N T H | MINH THI/, TRAN THI NHU MAI, NGO T H | THUAN, L^ TH| PHUONG DUNG Khpa Hda hpe - Trudng D^i hpc KHTN - DHQG HN SUMMARY Twelve hydrazone derivatives of gluconic acid fiave been synthesized via sodium gluconate, ethyl ester and hydrazide of gluconic acid. These structure and biological activities have been identified. M d DAU Trong mdt sdcOng trinh trudc ddy [1], chung tdi da thOng bdo v l phuong phdp oxi hda xuc tdc chpn tpc glucoza thdnh axit gluconic. Mgt khdc, nhu ehung ta da bilt, tdp chit hydrazon cua nhilu logi axit khde nhau thudng Id nhOng hpp chit cd hogt tfnh sinh hpc dg CHO COONa COOC2H5 (CHOH), - ^ 2 0 ^ (CH0H)4 -£lll^5V (CHOH). O2, XI CH2OH (I) I CH2OH (II) dang [2,3]. Trong bdi bdo ndy, chijng tdi nghign cUu tong hpp mpt day hydrazon cua axit gluconic thdng qua mpt day chuyin hda tQ axit gluconic thdnh mudi natri, etyt este, hydrazit vd cudi cung thdnh cdc hydrazon. CONHNH2 ili^::^ j CH2OH (III) R' J^ (^m-N=C^y _^L^(LoH), I tHiOH (IV) V , ^ /4 CH2 CH2OH (V,.|2) dddyR' vaP^ = H, CH}, phenyl M,... Mudi natri gtuconat nhgn dupc bdng q d trinh oxi hda glueozo trgn xuc tde nano Au/MCM-41, sQ dgng dung djch NaQH td tdc nhdn chinh pH ddng thPi eung td tde nhdn tgo mudi. Higu sud't sdn phlm cua qud trinh ndy dgt 80%. Clu tgo cua mud'i ndy dupe xdc djnh bdi pho hdng ngogi vd phd cdng hudng tQ hgt nhdn. (s, 2H, C-H2); 3,79 (d, IH, Z^-W,^)•, 4,00 (s, IH, C3-H) vd4,1 (s, IH, C2-H). Trgn phd ^^C-NMR thiy rO tfn higu cua 6 cacbon Qng vdi dp chuyin djch hda hpc nhu sau: (5ppm): 62,66 (Ce); 71,03 (C5); 71,27 (C,); 71,58 (C2); 74,09 (C,) vd 178,76 (C„ tQc Id CO). Trin phd hdng ngogi ed cdc dinh hip thg d 3.542, Bdng phdn Qng e d mudi natrigtucenat vdi etyt bremua 3.432, 3.313 vd 3.159cm"^ dde trung eho dao dOng hda trong thdi gian Idu ddi (4 - 5 ngdy) da nhgn dupc etyt trj cilia nhdm OH. Ngodi ra trgn phO cd dinh hip thg d 1.630em"\ dgc trung cho dao dfng hda trj cua ion gtuconat (III) vPi higu sd't khodng 70%. Trgn phd hdng cacboxytat (CO). ngogi cug hpp chit ndy thiy x d t hign 4 dinh hip thg treng viing tQ 3.200 din 3.540em"' dgc trung che dao Trgn phd cOng hudng tQ proton ghi trong dung mOi D2Q trgn mdy AV 500 Bruker cho thd'y d c tfn higu cfng dpng hda trj eua cdc nhdm OH aneol. Dgc bigt trdn phi hudng tuong Qng vdi dO chuyin djch hda hpc cua d c x d t hign dinh hip thg rit dgc trUng ehe dae ddng hda proton nhu sau: (5ppm, JH^): 3,64(d, IH, C5-H, 1); 3,74 trj cua nhdm CO este d 1.718cm"\ Hda hpc & U n g d u n g Si 20 (io4)/2oog ceo TQ etyt gtuconat, khi phdn Qng vdi hydrazin hydrat 80%, da nhdn dope gluconyt hydrazit (I) vPi higu s d t 40 - 50%. Trgn phd hdng ngogi cijg hydrazit cd vung hd'p thg rdng treng khodng 3.000 - 3.600cm"\ cd te Id dae dpng hda trj cua cdc nhdm QH, NH vd NH2, nhung dgc bigt cd cdc dinh hip thg d 1.655cm"\ dgc trgng cho dae dgng hda trj cCia nhdm CO amit (amit 1) vd 1.626cm"' dgc trung ehe dao ddng biln dgng e d nhdm NH2 (5NH2- vgeh gmit 2). Trgn phd cdng hodng tU proton e d hydrgzit, ghi trong dung mdi dimetylsunfoxit (DMSOde), thd'y xud't hign tfn higu cpng hudng Qng vdi 14 proton trong phdn tQ vdi dd chuyin djch hdg hpc nhg sau: (5ppm): 8,98 (s, IH, NH); 4,08 (d, 2H, NHj, 3,8Hz); 3,84-3,39 (m, 4H, C2-H, C3-H, C^-H, C5-H); 1,87 vd 1,04 (m, 2H, CH2); 1,78 (s, 5H, cdc proton cua 5 nhdm OH). Khi nggng tg hydrazit cua axit gluconic vdi d c andehit hoge xeton thdm (hoge bdo thom) da nhgn dope mpt day cdc din x d t hydrazon toong Qng (V,.,,). Cdc hydrazon dig la cdc chit rdn k i t tinh, cd nhigt dd ndng chdy rd rdng vd gid trj R, trgn sdc ky bdn mdng khdc vdi R, cua cdc chit diu. Kit qud dope gidi thigu d bing 1. Bing 1: Cdc d3n xuit hydrazon cua axit gluconic (V,.,,) H0CH2-(CH0H),-C0-NH-N=Cr R Sti.V R' 1° T R; HlOu su^t, % Ph(f hdng ngo?!, cm'^ voH vd VNH VCO VCN Nh6m khdc 1 CeHs- H 75-76 0.8 40 3445-3167 1666 1621 1571 - 2 P-CH3C6H4- H 149-150 0,6 55 3399-3152 1617 1566 - 3 p-CtCeHr H 199-200 0,79 60 3440-3100 1626 1588 819 (01) 4 p-BrCeH*- H 226-227 0,78 42 3450-3406 1619 1584 805 (Br) 5 0-O2N CgH^- H 185-186 0,6 60 3543-3156 1623 1571 1519,1343 (NO2) 1610 6 m-OzN C6H4- H 229-230 0,7 59 3445-3102 1678 1524 (NO2) 1631 7 P-O2N C6H4- H 305-306 0,52 42 3425-3176 1625 1524,1348 1599 1524.1343 (NO2) 8 0-OHC6H4- H 219-220 0.74 58 3462-3044 1621 1571 - 9 p-(CH3)2N C6H4- H 264-265 0.75 37 2903 - 1598 - 10 3-(CH30)-4-(0H) CsHs- H 160-161 0.45 51 3484-3329 1630 1602 1030 (C(x;) 11 3,4-(0CH20)- CsHj- H 205-206 0,74 43 3100-2915 1651 1630 1601 1033 (COC) 12 CeHs- CH3 110-111 0.71 68 3053-2926 1662 1600 1563 - * Bin mdng siticageL Hi dung mdi: n-hexan:Axetpn = 2:1 (Thep thi tfch) O)) Hda hpc & Ung dung Si 20 (io4)/2oog Trgn phd hdng ngogi ciJa cdc hydrazon diu thiy x d t hign 3 - 4 dinh hip thg trong vung 3.000 - 3.500em"' dgc trung cho dao ddng hda trj ciJa cdc nhdm OH vd NH. Dinh hip thg dgc trung che nhdm CO (amit) ndm trong vung 1.600 - 1.662cm"' vd dinh ddc trung cho dao ddng hda trj cua nhdm C=N d khodng 1.563- 1.602cm'\ Ngodi ra cung cdn cdc dinh hip thg ddc trung eho dae ddng c d cdc nhdm khdc (NO2, halogen). Phd cdng hudng tQ proton eua hydrazon V7 (sdn phlm ngUng tg e d gluconyt vdi p-nitrobenzandehit) che thiy cdc tfn higu cpng hudng cua cdc proton trong phdn tQ cd dd chuyen djch hda hpe nhu sau (5, ppm): nS': HO ^CH CH C NH-N=CH OH 8,86 (s, IH, CH=); 8,37 (d, 2H, Cs-H vd C9-H, J = 8,5Hz); 8.16 (d, 2H, C7-H vd C,o-H, J = 8,5Hz); 4,3 (t, 3H, C3-H, C4-H vd C5-H, J = 5,0 Hz); 3,44 (m, 6H, 5H cua 5 nhdm OH vd C%). NO, logi vi sinh vdt dupc thQ nghigm td: Cdu khuIn Gram (+): Staphylococcus epidermidis (S.e); Trgc khuIn Gram (-): Klesieila pneumonia (K.p) vd nim men: Candida albicans (Ca). Dung djch thQ nghigm dQpc nhd vdo ede 10 dgc trgn nin thgch da ciy vi sinh vdt vPi ede mQc lOOnl vd 150|it. Hogt tfnh khdng vi sinh vdt dQpc ddnh gid thee dp Idn cua duPng kfnh vdng trdn vd khdn (mm). Kit q d dupe gidi thigu d bing 2. Cdc hydrazcn cung dupe ehung tdi gQi tdi Phdng Nghign cQu Vi sinh - Bgnh vign 19/8 (Bg COng an) de thQ nghigm hogt tfnh khdng khuin vd chdng nim. Cdc ehd't thQ nghigm dQpc pha d ndng dp 5mg/mt. Chung Bing 2: Hogt tfnh khdng khuIn vd chlTng nl'm ciJa cdc hydrazon (V,.,:) K.p (Gr -) S.e (Gr *) C a (Nd'm men) HIdrazon V IOOMI 150MI lOOnl 150nt lOOnt 150^t 12 0 10 13 10 0 13 13 13 22 17 22 25 20 20 25 20 22 11 10 10 10 0 13 10 10 11 18 18 20 18 20 15 18 17 17 10 13 0 12 0 12 12 0 12 15 15 0 20 0 15 20 10 15 12 20 0 22 14 20 '•,< 1 2 3 4 5 6 7 8 9 10 11 12 Kit q d trgn cho thiy hlu hit d c hydrazon diu cd khd ndng khdng khdn cd Gr (+) vd Gr (-), cung nhu chdng nd'm men d mQc ddng chu y, nhlt td 6 mQc 150^1. Hda hpc & Ung d u n g Si 20 (104)120og ceo n. THi;C NGHIEM * Tdng h(fp natri gluconat (II): Hda tan 49,5 gam glueozo monehydrat vdo trong 500ml nude rdi chuyin vdo binh phdn Qng cd chQa 0,05 gam xuc tde Au/MCM41. Khdng khf dupe cung d p vdi td'c dp 20mi/phut, dilu chinh bdng Flo-Meter 110, ddng thdi dn djnh nhigt dp d 50°C. Dilu chinh pH din 9 bdng dung djch NaOH 0,5M vd thgc hign phdn Qng oxi hda glueozo. Theo thdi gian, axit sinh ra Idm pH cua dung djch phdn Qng gidm ddn, vl vgy treng thdi gian phdn Qng, lign tgc thgm kilm d l dn djnh pH d 9. Lgpng kilm tigg tdn trong khi phdn Qng tgong Qng vPi IQpng axit sinh ra. Tilp tgc thgc hign phdn Qng din khi pH khdng ddi. Lpc Id'y dung djch phdn Qng. Chuyin dung djch ndy vdo cd'c, thgm vdo 150ml cdn tuygt ddi, dua vdo thilt bj tdm Ignh, nhigt dp ~ 4''C treng 24 gid, tinh t h i mud'i natri gluccnat tgo thdnh ldng d ddy cd'c. Lpc ggn lly tinh t h i vd rQg sgch bdng edn tuygt ddi. Ldm khO d nhigt dO thudng trong 1 ngdy. Mudi thu dupc hod tan Igi trong nuPc, sau dd kit tinh tgi trong cdn Ignh. Lpc r d vd sly khd sdn phlm d 80°C, dupe tinh t h i mudi natri gtuconat mdu trdng vdi higu sd't khddng 80%. * Tdng h(fp etyl gluconat (III): Hdn hpp phdn Qng gdm lOg md't natri gtuconat, 5,1 mt etyt bromua (d = 1,46g/ml), (lupng etyt bremua dupe lly du 1,5 tin d l phdnOng cd t h i h d n todn hOn) trong 50mt etanol. Oun sdi hdn hpp phdn Qng trdng sudt 4 - 5 ngdy. D l ngugi rdi pha toang hdn hpp bdng nudc d l hod tan hit mudi natri bremua. Tdch rifing tdp hOu co, Idm khd bdng Na2C03 khan, ed't Icgi etyt bremua du. Lpc kg't tijg rdn tdch ra rdi tinh c h l Igi, thu dQpc 7,3 gam (70%) este etyt gtuconat. * Tdng h(rp gluconyl hydrazit (IV): Hdn hpp phdn Qng gdm 1 gam etyt gtuconat vd 0,35mt hydrazin hydrat 80% treng 30mt etanol, thgm vdo vdi gipt axit axetic. Dun sdi hdn hpp treng 8 giP. Tilp tgc thgm vdo 0,35mi hydrazin hydrat 80% nQa vd tgi dun sdi treng 8 gid. CO cgn bdt dung mdi rdi d l ngupt, thu dupc gluconyt hydrazit d dgng diu dgc vdi higu suit khodng 40 - 50%. * Pht/ong phdp chung tdng h^p cdc hydrazon cua axit gluconic (V1.12): Hdn hpp phdn Qng gdm 0,005mol (1,05g) gluconyt hydrazit (IV) vd 0,005mol hpp chit eaebonyl (andehit hoge xeton) treng 30mt etanol, thSm vdo vdi gipt axit axetic. Dun sdi hdi luu hdn hpp phdn Qng khodng 1 0 - 2 0 gid. O l ngupi din nhigt dg phdng rdi tpc hut kit tua tdch ra (Cd t h i cho bay hdi bdt dung mdi phdn Qng). Kit qud dupc gidi thigu d bing 1. III. KET LU^N TQ phdn Qng oxi hda glueozo tgo mudi natri gluconat, dupc chuyin qua etyt este rdi hydrazit md tQ dd ngung \\) vdi cdc hpp ehd't eaebonyl d l tgo thdnh mpt ddy 12 hpp chit hydrazon cua axit gluconic. Clu tgo vd hogt tfnh sinh hpc cug cdc hydrazon da dupe xdc djnh. TAI Lieu THAM KHAO 1. Nguyin Thj Minh Thu, Trin Thj Nhu Mai, Ngd Thj Thdn. Chit^o xuc tie Au/MCt^-41 cho phin Ung oxi hda chpn ipc glucpzd Tgp ehf Khoa hpc, KHTN vd CN, DHQG Hd Npi 8/2009. 2. Hd Thj Digp, Luin in Phd tiin si Hda hpc HUu cd - TruPng Ogi hpc Tdng hpp Hd Npi - Hd Npi, 1989. 3. Trdn Qude SPn, Nguygn Tiln COng, Phgm Thj Hoa, T^p ehf Hda hpc, T.43, sd6, tr.725 (2005). 4. Nguyin Minh Thdo, Vu Minh Tdn, Phgm Vdn Nhigu, T9P ehf Hda hpe, T.42, sd 3, tr.311 (2004).» NgiMphdn bifn: PGS, TS NGUYEN DINH THANH Cdng trinh niy dUdc hoin thinh vdi si/ hd trp tii ehfnh cua ehUdng trinh nghiin cUu khda hpc cua D^i hpe Qude gia Hi NOi (Di tii QT-09-31). O)) Hda hpc & Lfng dung Si 20 (i04)/2oog