Tổng hợp một số dẫn xuất Hyđrazon của Axit Gluconic

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