V6l MOT SO ANDEHIT THOM TONG HOP VA NGUNG TU 2-METOXY-4-(3-METYLFUROXAN-4-YL)-5-NITROPHENO-XIAXETYLHIDRAZIN

Tap chi Hoa hoc, T. 48 (6), Tr. 687 - 692, 2010. TONG HOP VA NGUNG TU 2-METOXY-4-(3-METYLFUROXAN-4-YL)-5-NITROPHENOXIAXETYLHIDRAZIN V6l MOT SO ANDEHIT THOM "••'•'. De'nTda. sogn3-11-2009. HO A N G THI TUYET LAN', NGUYEN HUU DINH' 'Trudng Dgi hgc Giao thong van tdi 'Trudng Dgi hgc Suphgm Hd Ngi. ABSTRACT 2-Methoxy-4-(3-methylfuroxan-4-yl)-5-nitrophenoxyacetylhydrazine synthesized from 2methoxy-4-(3-methylfuroxan-4-yl)-5-nitrophenoxyacetic acid was condensed with aromatic or heterocyclic aldehyde to give nine hydrazide-hydrazones. The structure of reported compounds have been confirmed by IR, 'H-NMR and '^C-NMR spectra. It is shown that the hydrazidehydrazones exist as syn and anti conformers at CO-NH hydrazide single bond. thdng bdo viec tao vdng furoxan tQ nhanh allyl cua axit isoeugenoxyaxetic (kf hieu A) nhd dd da dilu c h i dugc axit 2-metoxy-4-(3metylfuroxan-4-yl)-5-nitrophenoxyaxetic. Bai bdo nay trinh bdy kit qua tdng hgp va ngung ty 2-metoxy-4-(3-metylfuraxan-4-yl)-5nitrophenoxyaxetylhidrazin (kf hieu Hy) vdi mgt so andehit thom.. I - Md DAU Cac hgp chdt chQa vdng furoxan (1,2,5oxadiazole-2-oxit) thugc loai cac chdt giai phdng nita oxit (NO) trong dilu kien sinh ly (trong ca thi) gid'ng nhu glyxeryl trinitrat, hoac natri nitropmsside da dugc dung trong tri lieu benh tim mach [1,2]. Hien nay viec tong hgp vd nghien cQu cac hgp chdt cd chQa vdng furoxan dang thu hut su chu y cua cac nhd hda duac [3, 4].. II - THUC NGHIEM Cdc chdt dugc tdng hgp theo sa dd sau day:. Trong cdng trinh trudc [5], chung tdi da. ur. 02N^,^j:^OCH2COOH L !l 1|EtOH^)N2H4. .yv C/N-Q^N. OCH3 (A). 02N^^;x.,^OCH2C=0 T || I li~% ^N.^,N. 02N..„^.^j;rx^OCH2C=0 ArCHO. ^H3C\J^. 0CH3. NHN=CHAr OCH3. „/N,_.N (Hy). (1 - 9). So do tdng hgfp cdc chdt 2-Metoxy-4-(3-metylfuroxan-4-yl)-5nitrophenoxyaxetylhidrazin (Hy) dugc dieu c h i bang cdch chuyen axit 2-metoxy-4-(3-. metylfuroxan-4-yl)-5-nitrophenoxyaxetic (A) [5] thanh etyl este rdi dun hoi luu vdi Mgng du hidrazin hidrat. Kit tinh lai trong DMF-nudc 1: 687.

1, thu dugc cac tinh the hinh kim mau vang, ndng chay d 212°C, Meu suat 67%. Ngung ty Hy vdi cac andeMt dugc tiln hanh nhu sau: Dun hdi luu hdn hgp gom 1 mmol Hy, 1 mmol andeMt tham (hoac di vdng) va mgt lugng dioxan tdi tMeu (vQa du tan hit chat ddu) ttong vdng 8-^10 gid. Sau dd lam lanh hdn hgp phan Qng, Igc Idy chat rdn, kit tinh lai ttong. dung mdi tMch hgp, thu dugc cdc MdrazitMdrazon 1 - 9 (bang 1). NMet do ndng chay do tten may GALLENKAMP MPD-350. Pho IR ghi d dang vien nen vdi KBr tren may IMPACT 410 Nicolet. Pho NMR dugc ghi tren may Bnicker (500 MHz) ttong d^-DMSO tai Vien Khoa hgc va Cdng nghe Viet Nam.. Bdng I: Kit qua tong hgp cac hidrazit-hidrazon 1 - 9 Kl. Ar. Meu. Dung mdi kit tinh. Dang bl ngoai. Dilm chay, °C. Hieu suat, %. 4-CH3C6H4-. 1. Dioxan - Etanol. Hinh kim, mau vang. 206. 69. 2-aC6H4-. 2. DMF - Etanol. Hinh kim, mau vang. 209-210. 72. 2-02NC6H4-. 3. Dioxan - Nudc. Hinh tdm, mau vang. 213-214. 78. 4-02NC6H4-. 4. Dioxan - Nudc. Hinh kim, mau vang. 228. 78. 2-HOC6H4-. 5. DMF - Nudc. Hinh vay, mau vang. 198. 74. 3-HOC6H4-. 6. Dioxan - Nudc. Hinh tdm, man ttdng. 227-228. 69. 3-CH30C6H4-. 7. Dioxan - Nudc. Hinh kim, mau vang. 199. 57. 2,4-(HO)2QH3-. 8. DMF - Nudc. Hinh kim, vang dam. 240-241. 63. 3-Mdolyl. 9. Etanol - Nudc. Hinh kim, mau vang. 242-243. 63. III - KET QUA VA THAO LUAN Mgt sd van hdp thy tten phd hdng ngoai cua cac hgp chat ngMen cQu dugc het ke d bang 2. Bdng 2: Mgt sd van pho hong ngoai cua cac hgp chat nghien cQu, cm"' Hgp chat. VCH. Vc=o. 'Vc=N. C=C. furoxan. v=c-o. -/3333, 3290. 3053,2917, 2860. 1683. (1622), 1578, 1520. 1464. 1276. -/3199. 3098, 2977, 2855. 1691. 1615, 1582, 1526. 1481. 1274. 2. -/3344. 3069, 2935, 2851. 1707. 1623,1582, 1525. 1467. 1279. 3. -/3210. 3081,2925,2861. 1712. 1617,1580, 1527. 1470. 1275. 4. -/3194. 3095, 2975, 2862. 1691. 1611, 1583,1530. 1485. 1276. 5. 3100/3192. 3000, 2930,2852. 1686. 1618, 1590, 1532. 1491. 1274. 6. 3290 / 3200. 3070,2935,2850. 1702. 1612,1600,1531. 1455. 1278. 7. -/3199. 3093, 2930,2859. 1684. 1611,1583, 1523. 1470. 1250. 8. 3454/3143. 3065,2923,2850. 1670. 1611, 1587,1515. 1442. 1275. 9. -/3250, 3200. 3058, 2923,2859. 1694. 1614,1575, 1523. 1437. 1274. Hy 1. 688. VNO VOH/VNH.

Cac van hdp thy hong ngoai liet ke d bang 2 diu phu hgp vdi cau tao cua cac chdt nghien cQu. Tren pho cua cdc hidrazit-hidrazon 1 - 9 ben canh van hap thy manh d 1676 - 1712 cm dac trung cho nhdm C=6 hidrazit ludn xudt hien mgt van kha manh g 1611 - 1623 cm"'. Van nay la thi hien dao dgng hda tri ciia nhdm C=N hidrazon. Dao dgng khung cua nhan thom (vc^c VC=N) thudng thi hien bdi vai ba van trong khoang 1500 - 1600 cm"', trong sd dd van d tdn sd cao nhdt cd the vugt 1600 cm"' va xen phu vdi van hdp thy cua nhdm C=N hidrazon. Vi vay trong bang 2 chung dugc liet ke chung vao cot Vc=N. c=c- van hap thy ghi trong ddu ngoac don d 1622 cm"' cua Hy la thugc dao dgng bie'n dang 2 Mdi keo cua nhdm NH2 hydrazin. Van hap thu manh d 1437 - 1470 cm"' d phd cua cac chat. .iL!L..:i. trong bang 2 dugc quy cho nhdm 0-N-O furoxan la dya theo tai lieu [6]. Khac vdi Hy, pho 'H NMR cua 1 - 9 kha phQc tap vi bao gdm 2 bg tfn hieu dan xen vao nhau, cudng do tuong ddi cua 2 bg la 2:1. Cac nhdm nguyen tu d hgp phdn hidrazit dugc ghi sd tQ 1 den 10, d hgp phan andehit tQ 11 - 17 trong dd sd 11 gianh cho C cua nhan benzen dfnh true tilp vdi Ci (C cua nhdm -N=CH-), rieng vdi vdng indol, so chi vi trf dugc ghi nhu d cdng thQc dudi day. Viec quy kit cac van cdng hudng 'H-NMR mgt mat dya vao do chuyin dich hod hgc, do bdi va hdng sd tach, mat khde dya vao cac dQ lieu d cdc day hgp chdt tugng ty ma chung tdi da nghien cQu mgt each cd he thdng [7, 8], mdt sd trudng hgp da su dyng phd 2D NMR, thf dy nhu d hinh 1. Kit qua phan tfch p h d ' H NMR dugc liet ke d bang 3.. ^LU" "1., ;flJXLJ£jli @ C5. CO). 'S3>. cfife. ©. r. @ o SM-iiiM. 'H/ CS' '• <. Hinh 1: Mdt phdn phd HMBC cua hgp chat 9 ™ 5,^>;^ H3C, 9 8. ^CH,C=0. '0CH3. NHN=CH^. ,,,. '=VNHI Sd chi vi trf dung d l phan tfch pho NMR cua cac hidazit-hidazon. Bang 3 cho thdy, trong khi mdi nhdm proton d Hy chi cho 1 van cdng hudng thi hdu hit cdc nhdm proton d cdc hidrazit-hidrazon diu cho 2 van cdng hudng cd Mnh dang nhu nhau vdi do chuyin dich hoa hgc khac nhau rat ft. Hien tugng nay thudng gap d cac day hidrazithidrazon vd da dugc chung tdi chQng minh rdng. dd la do cdu dang syn va cdu dang anti d nhdm CO-NH hidrazit gay nen [9]. Ti le moi cua chung tfnh theo cudng do tten pho proton la 2:1. Tfn hieu cua cac proton d hgp phdn hidrazit (H3, H6, H7a, H7b, HIO, NH)' biln ddi rdt ft khi chuyen tQ hgp chat nay sang hgp chat kia vi cac proton dd d xa phan thay ddi cdu tao cua phan 689.

chat kia.. tu. Sy xudt hien van dan b 1,96 - 8,69 ppm chQng td sy cd mat cua nhdm CH=N hidrazon (Hi). Van pho cua proton nhdm nay va cua cdc proton khac thugc hgp phdn andehit (HI2 HI7) thay doi nhilu phu hgp vdi sy thay doi cdu tao cua cdc hgp phdn andehit tQ chat nay sang. O phan tQ cdc hidrazit-hidrazon 1 - 9 cd khoang 1 8 - 1 9 nguyen tu C nhtmg tren pho '^C NMR ddi vdi nhilu trudng hgp cd tdi gdn 30 tfn hieu cdng hudng (bang 4).. Bdng 3: Tfn hieu 'H-NMR cua cac hgp chat nghien cQu, 5, ppm; J, Hz Hy. 1 2. H3 H6 H7a 7,42 s 8,00 s 4,74 s 7,43 s, 7,84 s, 7,45 s 7,93 s 7,42 s, 7,86 s, 7,94 s. 7,43 s, 7,87 s, 5,45 s 7,45 s 7,94 s 4,97 s. 4. 7,43 s, 7,87 s, 7,93 s 7,42 s, 7,85 s, 7,45 s 7,95 s. 6. 7 8 9. HIO 3,96 s 2,01s. Hi. HN. -. 9,35 s. NH^: 4,37 s. 8,01 s, 11.64 s, H12,16: 7,62 d; 7,59 d; J 8; H13, 15: 8,24 s 11.65 s 7,26 d; 7,23 d; J 8; H17: 2,34 s; 2,33; s. 8,42 s, 11,86 s, H13: 7,53 d; J 7,5; H14: 7,45 t; J 7,5; H15: 7,42 t; J 7,5; H16: 8,03 t;7,97 t; J 8,68 s 7,5. 3,97 s, 2,02 s. 8,42 s, 11,98 s, H13: 8,13 d; 8,07 d; J 8; H14: 7,81 t; J 7,5; H15: 7,68 t; J 7,5; H16: 8,06 d; J 8,69 s 8,5. 3,97 s. 2,02 s. 8,14 s, 11,99 s, H12,16: 7,99 d; J 7; H13, 15: 8,28 d. 8,38 s 3.97 s, 2,02 s, 8,34 s, 11,65 s, H13: 6,92 d; J 7; H14: 7,25 t; 7,30 t; J 7,5; H15: 6,87 t; 6,91 t; J 7,5; H16: 7,72 8,51s 3.98 s d; 7,55; d; J 7,5; OH: 10,95 s; 10,05 s.. 5,51s 4,99 s 5,43 s 4,96 s. 7,43 s, 7,96 s, 5,44 s 3.97 s, 2,02 s, 7,84 s, 11.65 s, H12: 7,13 s; 7,17 s; H14: 6,83 d; J 7; 7,46 s 7,93 s 4,94 s 3.98 s 2,35 s 8,18 s 11.66 s 1,5; H15: 7,24 t; J 8; H16: 7,10 d; J 8; OH: 9,61 s . 7,43 s, 7,85 s, 5,46 s 3.98 s, 2,03 s. 8,02 s, 11,70 s, H12: 7,30 s; H14: 7,01 d; J 7; H15: 7,36 t; J 7,5; H16: 7,28 m;H17: 3,80 s. 8,26 s 7,45 s 7,94 s 4,95 s 3.99 s 7,41 s, 7,83 s, 7,45 s 7,94 s 7,43 s, 7,87 s, 7,45 s 7,97 s. 5,38 s 3,98 s, 2,02 s. 4,93 s 3,96 s 5,47 s 3,98 s. 2,02 s. 4,92 s. 8,21 s, 11,11 s, 8,36 s 11,43 s 8,23 s, 11,38 s, 8,44 s 11,36s. De quy kit cdc tfn hieu '^C NMR va mdt so tfn hieu 'H NMR, chung tdi da sQ dyng pho 2D NMR. Thf dy, ddi vdi hgp chat 9, dya vao do chuyin dich hda hgc da quy kit dugc mgt cdch chdc chdn cdc van don cua cac proton H7a, H7b, CIO, Hi. Cac van giao (cross peak) cua chung tren pho HSQC giup nhan ra cdc tfn hieu cua C7a, C7b, CIO, Ci. Tren pho HMBC giup nhan ra cac tfn hieu Cl, C2, C8, C9 va C=0. Tfn hieu cua H3 va H6 deu la nhung van dan, H6 d vi tri ortho so vdi nhdm NO2 cdn H3 d vi trf ortho so 690. Hkhac. 5,44 s 3.97 s, 2,03 s 4,93 s 3.98 s 5,47 s 3.97 s, 2,02 s, 4,96 s 3.98 s. 3. 5. H7b. H13: 6,30 s; H15: 6,35 m; H16: 7,32 d; 7,50 d; J 8,5; 20H:11,75 s; 9,94 s. H12: 7,82 s; 7,81 s; H14: 8,15 d; 8,14 d; J 7,5; H15: 7,15 t; 7,14 t; J 7,5; H16: 7,21 t; 7,19 t; J 7,5; H17: 7,45 d; NH(Indole): 11,56 s.. vdi nhdm OCH3 nen tfn hieu cua H6 d trudng ylu ban, vi t h i van dan d 7,87 ppm dugc quy cho H6. Tfn hieu cua H3 dan xen vdi tm Meu cua H17 nhung vdn nhan ra dugc nhd van giao cua nd vdi C8, Cl va C5 d thdp hgn so vdi cac van giao cua H17 vdi C19 va C15. Tfn hieu cua C12, C19, C13 dugc nhan ra nhd cac van giao c; a vd d; b wa. e ciia chung vdi Hi. Tm hieu cua H14 gom 2 van ddi vdi cudng do 0,77 H vd 0,33 H, van cd cudng do 0,33 H xen phu vdi van don cua Hi. Cac van giao/, gvah cua H14 cho phep.

nhan ra C18, C16 va C13. Tfn hieu cua H15 va H16 diu cd dang van ba vdi do chuyin dich hda hoc gdn nhau, chung dugc phan biet nhu sau: H16 cd van giao k va / vdi C18 va C14; H15 cd van giao mvan vdi C19 va C17. Nhu vay pho '^C NMR cua cac hidrazithidrazon 2, 3, 5 va 9 cung gom 2 bg tfn hieu nhu phd 'H-NMR, nhung tfn hieu cua '^C-NMR d cdu dang cd sd moi ft ban da khdng dii manh nen khdng quan sat dugc ddi vdi mgi vi trf. (bang 4). Tuy vay cdc sd lieu thu dugc la hoan toan phu hgp vdi cdu tnic du kiln. Tren pho ESI MS cua hidrazon 2 (M = 461) cung nhu cua hidrazon 6 (M = 443) pic cd cudng do ldn nhdt (100%) la pic M+ff (m/z = 462 va 444 tuong Qng). Canh pic m/z = 462 cd pic m/z = 464 vdi cudng do 40% phu hgp vdi 1 nguyen tQ Cl trong phan tu 2. Ngoai ra d phd cua hai chdt diu cd pic M-l-Na vdi gia tri m/z tuang Qng 466 vd 484, cudng do diu bdng 25%.. Bdng 4: Tin hieu '^C N M R cua H y va cdc hgfp chdt 2, 3, 5, 9,Sp p m Hy. 2. Cl C2 C3 C4 C5 C6 C7a C7b C8 C9 CIO C=0 Ci Cll C12 C13 C14 C15 C16. 149,01 153,64 114,58 115,06 139,91 110,27 67,13 56,85 156,32 113,65 7,57 165,77 -. 149,27 153,36 114,46 114,50 140,01 109,88 65,83; 56,80; 56,89 156,34; 113,68;7,61;168,35; 163,70 140,29; 143,84 131,47 133,00 129,87 131,15 127,11 127,53 -. C17; C18; C19. -. -. 3 149,24 153,36 114,48 114,55 139,77 109,86 65,79; 56,81; 156,34 113,69 7,61; 168,48 140,01 128,06 148,02 124,50 130,66 133,51 128,56. IV - KET LUAN Bang phan Qng ngung ty 2-metoxy-4-(3metylfuroxan-4-yl)-5-nittophenoxyaxetylhidrazin tdng hap tQ axit 2-metoxy-4-(3metylfuroxan-4-yl)-5-nitrophenoxyaxetic vdi mgt sd andehit tham hoac di vdng da thu dugc 9 hidrazit-hidrazon cd chQa vdng furoxan. Cdu tnic cua cdc hidrazit-hidrazon da duac xdc dinh nhd phd IR, 'H-NMR va "C-NMR. DQ lieu phd NMR thu dugc cho thay cdc hidrazit-hidrazon. 5. 9. 149,30; 148,92 153,36; 153,62 114,43; 114,48 114,69; 115,24 139,98; 139,90 109,87; 110,41 65,78; 67,07 56,78; 56,88 156,43; 156,36 113,69;7,59; 167,80; 163,27 141,89; 148,09 131,59; 131,30 157,30; 116,13; 116,35 129,14; 126,54 118,57;119,91; 119,35. 149,48; 149,19 153,71; 153,48 114,58; 114,48 114,67; 115,19 139,99; 109,89; 110,36 66,14; 67,41 56,86; 56,93 156,49; 113,79;7,65; 167,23; 162,50 141,83; 145,26 130,70; 111,32;121,84; 120,67; 120,52 122,72; -. -. 111,94; 137,16; 124,33; 124,12. -. nghien cQu ton tai d 2 cau dang syn va anti b lien kit dan CO-NH hidrazit. TAI. LIEU THAM K H A O. 1. S. V. Pirogov, S. F. Mel'nikova, I. V. Zelinskii, T. V. Romanova, N. P. Spiridonova, N. A. Medvedeva, T. V. Bulartina. Russ. Patent RU 2240321 C2 20 Nov 2004. 2. R. Ferioli, A. Fazzini, G. C. Folco, R. 691.

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