Tổng hợp và tính chất của một số hợp chất 2,4 dihydroxyquinolin thế có chứa hợp phần đường

I HC QUC GIA H NI TRNG I HC KHOA HC T NHIấN DNG THANH NGA TNG HP V TNH CHT CA MT S HP CHT 2, 4-DIHYDROXYQUINOLIN TH Cể CHA HP PHN NG LUN VN THC S KHOA HC Chuyờn ngnh: Húa Hu C Mó s : 60440114 H Ni 2017 I HC QUC GIA H NI TRNG I HC KHOA HC T NHIấN DNG THANH NGA TNG HP V TNH CHT CA MT S HP CHT 2, 4-DIHYDROXYQUINOLIN TH Cể CHA HP PHN NG LUN VN THC S KHOA HC Chuyờn ngnh : Húa Hu c Mó s :60440114 Cỏn b hng dn: GS TS Nguyn ỡnh Thnh H Ni - 2017 LI CM N hon thnh lun ny, trc tiờn cho em gi li cam n chõn tiGS TS Nguyn ỡnh Thnh a giao ti, tn tỡnhhng dnv ch bo em sut thi gian thc hin lun tt nghip Em cng xin chõn thnh cm n cỏc Thy, cụ b mụn Hoỏ Hu C, cỏc anh ch, cỏc bn v cỏc em phũng Tng Hp Hu C I ó luụn to iu kin, ng viờn, trao i v giỳp em hon thnh lun vntt nghip ny H Ni, thỏng nm 2017 Hc viờn Dng Thanh Nga CC K HIU VIT TT 13 C NMR : 13carbon C-Nuclear Magnetic Resonance (Ph cng hng t ht nhõn carbon-13) DMSO-d6 : Dimethyl sulfoxide c deuteri húa nc : im núng chy IR : Infrared Spectroscopy (Ph hng ngoi) MS : Mass Spectrometry (Ph lng) H NMR :1H-Nuclear Magnetic Resonance(Ph cng hng t ht nhõnproton) : chuyn dch húa hc DANH MC BNG BNG 3.1 Kt qu ph IR ca mt s hp cht 2-methylquinolin-4(1H)-on th 51 BNG 3.2 Kt qu ph IR ca mt s dn xut ca hp cht 2-methylquinolin-4(1H)-on th 55 BNG 3.3.Kt qu ph IR ca mt s dn xut ca hp cht 4-cloro-2-methylquinolin-4(1H)-on th 56 DANH MC HèNH Hỡnh 3.1.Ph IR ca 4-hydroxyquinolin-2-on 44 Hỡnh 3.2.Ph IR ca 4-hydroxy-7-methylquinolin-2-on 45 Hỡnh 3.3.Ph 1H NMR ca 4-hydroxy-7-methylquinolin-2-on 46 Hỡnh 3.4 Ph 13C NMR ca 4-hydroxy-7-methylquinolin-2-on .47 Hỡnh 3.5 Ph 1H NMR ca hp cht 4-propynyloxyquinolin-2(1H)-on 48 Hỡnh 3.6 Ph 1H NMR ca 7-methyl-4-propynyoxyquinolin-2-on .49 Hỡnh 3.7 Ph 13C NMR ca 7-methyl-4-propynyloxylquinolin-2-on .50 Hỡnh 3.8.Ph IR ca 2-methylquinolin-4-on 52 Hỡnh 3.9.Ph IR ca 2,8-dimethylquinolin-4(1H)-on 52 Hỡnh 3.10.Ph 1H NMR ca hp cht 2-methylquinolin-4(1H)-on 53 Hỡnh 3.11.Ph 13C NMR ca hp cht 2-methylquinolin-4(1H)-on .54 Hỡnh 3.12 Ph IR ca 2,8-dimethyl-4-cloroquinolin 55 Hỡnh 3.13 Ph IR ca hp cht 4-azido-2,8-dimethylquinolin 57 Hỡnh 3.14 Ph 1H NMR ca hp cht 4-azido-2,8-dimethylquinolin 58 Hỡnh 3.15 Ph 13C NMR ca hp cht 4-azido-2,8-dimethylquinolin .59 Hỡnh 3.16 Ph 1H NMR ca hp cht 4-azido-2,6-dimethylquinolin .60 Hỡnh 3.17 Ph 13C NMR ca hp cht 4-azido-2,6-dimethylquinolin 61 Hỡnh 3.18 Ph 1H NMR caPhn ng click gia 4-azido-2-methylquinolin vi propagyl Tetre-O-acetyl--Dglucopyranoside 63 Hỡnh 3.19 Ph C NMR caPhn ng click gia 4-azido-2-methylquinolin vi propagyl Tetre-O-acetyl--Dglucopyranoside 64 MC LC M U CHNG TNG QUAN 10 1.1 TNG QUAN V QUINOLIN 10 1.1.1 Gii thiu v quinolin 10 1.1.2 Tớnh cht ca quinolin 10 1.1.3 Tng hp quinolin 11 1.2 TNG QUAN V CC 2-METHYLQUINOLIN-4(1H)-ON TH 14 1.2.1 Gii thiu v cỏc 2-methylquinolin-4(1H)-on v dn xut 14 1.2.2 Tớnh cht húa hc 15 1.2.3 Phn ng tng hp 2-methylquinolin-4(1H)-on v dn xut 18 1.2.1 Hoat tớnh sinh hc 19 1.3 TễNG QUAN Vấ PHAN NG CLICK 20 1.3.1 Gii thiu 20 1.3.2 Tng quan tỡnh hỡnh nghiờn cu 21 1.4 Tng hp 4-hydroxyquinolin 27 1.4.1 Tng hp t ethyl oxaloacetate 27 1.4.2 Tng hp t ester ethyl ethoxylmethylenemalonic 28 1.4.3 Tng hp t hp cht thm ortho disubstituted 28 1.4.4 Tng hp t ethyl acetoacetat 29 CHNG PHN THC NGHIM 31 2.1 TNG HP 2, 4-DIHYDROXYQUINOLIN TH 32 2.1.1 Tng hp 2, 4-dihydroxyquinolin 32 2.1.2 Tng hp 7-methyl-2,4-dihydroxyquinolin 32 2.2 TNG HP 4-PROPYNYLOXYQUINOLIN-2-ON TH 33 2.2.1 Tng hp 4-propargyloxyquinolin-2-on 33 2.2.2 Tng hp 7-methyl-4-propargyloxyquinolin-2-on 33 2.3 TNG HP MT S HP CHT -ENAMIN CA ETHYL ANILINOCROTONATE TH 34 2.4 TNG HP MT S HP CHT CA CC 2METHYLQUINOLIN-4-ON TH 35 2.4.1 Tng hp 2-methylquinolin-4-on 35 2.4.2 Tng hp 2,8-dimethylquinolin-4-on 35 2.4.3 Tng hp 2,6-dimethylquinolin-4-on 36 2.4.4 Tng hp 8-methoxy-2-methylquinolin-4-on 37 2.5 TNG HP DN XUT 4-CLORO-2-METHYLQUINOLIN TH 37 2.5.1 Tng hp 2-methy-4-clorolquinolin 37 2.5.2 Tng hp 2,6-dimethyl-4-cloroquinolin 38 2.5.3 Tng hp 2,8-dimethyl-4-cloroquinolin 39 2.5.4 Tng hp 8-methoxyl-2-methyl-4-cloroquinolin 39 2.6 TNGHP CC 4-AZIDO-2-METHYL-QUINOLIN TH 40 2.6 Tng hp 4-azido-2-methylquinolin 40 2.6.2 Tng hp 4-azido-2,8-dimethylquinolin 41 2.6.3 Tng hp 4-azido-2,6-dimethylquinolin 41 2.6 Tng hp 8-methoxy-4-azido-2-methylquinolin 41 2.7 PHN NG CLICK CA 4-AZIDO-2-METHYLQUINOLITH VI PROPARGYL TETRA-O-ACETYL--D-GLUCOPYRANOSIDE 42 Chng KT QU V THO LUN 43 3.1 TNG HP 4-HYDROXYQUINOLIN-2(1H)-ON TH 43 3.1.1 Tng hp 4-hydroxyquinolin-2(1H)-on 43 3.1.2 Tng hp 4-hydroxy-7-methylquinolin-2(1H)-on 44 3.2 TNG HP MT S 4-PROPARGYLOXYQUINOLIN-2(1H)-ON TH 47 3.2.1 Tng hp 4-propargyloxyquinolin-2-on 47 3.2.2 Tng hp 7-methyl-4-propargyloxyquinolin-2-on 47 3.3 TNG HP CC 2-METHYLQUINOLIN-4-ON TH 49 3.3.1 iu ch enamin 49 3.3.2 Phn ng úng vũng cỏc enamin 49 3.3.3 Ph hng ngoi ca cỏc hp cht ca 2-methylquinolon-4(1H)-on th 50 3.3.4 Ph cng hng t ca cỏc hp cht ca 2-methylquinolon4(1H)-on th 52 3.4 TNG HP MT S 4-CLORO-2-METHYLQUINOLIN 53 3.5 TNG HP MT S 4-AZIDO-2-METHYLQUINOLIN 55 3.5.1 Ph hng ngoi cỏc dn sut ca cỏc hp cht ca 2-metylquinolon4(1H)-on th 55 3.5.2.Ph cng hng t ca 4-azido-2,8-dimethylquinolin 56 3.5.3 Ph cng hng t ca 4-azido-2,6-dimethylquinolin 58 3.6 PHN NG CLICK CA 4-AZIDO-2-METHYLQUINOLIN VI PROPAGYL TETRA-O-ACETYL--D-GLUCOPYRANOSIDE 61 KT LUN 64 TI LIU THAM KHO 65 PH LC 74 M U T thi xa xa, ngi ta ó bit iu ch v s dng mt s hp cht hu c i sng nh: gim, cht mu hu c, ru ethylic Ngy cựng vi s phỏt trin manh m ca khoa hc k thut núi chung v húa hc núi riờng, húa hc v tng hp cỏc cht hu ccng ngy cng phỏt trin nhm tao cỏc hp cht phc v cho i sng ca ngi, c bit l cỏc hp cht cú hoat tớnh sinh hc cao i vi c th ngi v sinh vt Cỏc hp cht ny ngy cng tr nờn cú ý ngha quan trng v c ỏp dng vo lnh vc y hc cha tr cỏc cn bnh him nghốo, nõng cao sc khe cho ngi v ng vt Nh chỳng ta ó bit, quinolin-4(1H)-on l hp cht hu c i t dn xut ca quinolone vi hoat tớnh sinh hc cao Chng han nh chng viờm, khỏng nm, khỏng khun, cú thuc chng co git, gim au [6,17] Ngoi cỏc dn xut ca quinolone 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2,8-dimethylquinolin-4-on 75 Hỡnh 3.Ph cng hng t 13C ca hp cht 2,8-dimethylquinolin-4-on 3.ph cng hng t H 13 C caPhn ng click gia 4-azido-2- methylquinolith vi propargyl tetra-O-acetyl--D-glucopyranoside Hỡnh 4 Ph cụng hng t 1H ca phn ng click4-azido-2-methylquinolith vi propargyl tetra-O-acetyl--D-glucopyranoside 76 Hỡnh ph cng hng t 13C ca phn ng click gia 4-azido-2methylquinolith vi propargyl tetra-O-acetyl--D-glucopyranoside 77 Hỡnh Ph cng hng t 1H NMR ca hp cht 4-azido-8-methoxyl-2methylquinolin 78 79 [Type text] Page 59 ... Sự cộng hợp vào liên kết bội carbon-carbon R R X [X] R R + Sản phẩm phụ (X = O, NR,+SR,+NR) (Sự tạo thành vòng ba cạnh) EWG EWG EWG + EWG EWG EWG (EWG: Nhóm hút electron) (Một số cộng hợp Michael)... 29 CHNG PHN THC NGHIM 31 2.1 TNG HP 2, 4 -DIHYDROXYQUINOLIN TH 32 2.1.1 Tng hp 2, 4 -dihydroxyquinolin 32 2.1.2 Tng hp 7-methyl -2,4- dihydroxyquinolin 32 2.2 TNG HP 4-PROPYNYLOXYQUINOLIN-2-ON... sinh hc, hoỏ hc b mt, khoa hc vt liu, cụng ngh nano [55-57] 23 Sự cộng hợp vòng hoá R N N N + R R Cu(I) CH N N N R (Sự cộng hợp vòng hoá 1,3-lưỡng cực azide alkyn cuối mạch) Sự m vòng nucleophil