Tổng hợp một số hợp chất hữu cơ chứa dị vòng Piridin, thăm dò hoạt tính kháng khuẩn và khả năng ức chế ăn mòn kim loại của chúng

DAI HOC QUOC GIA H A Npi TRirdNG DAI HOC KHOA HOC Tl/ NHIEN * ô!# ã!# ftf^ *!ô 9S0 * * ^ * ^t# * ^ *J» rj* *J» »J* *J» *J» *J» yv-^ TEN DE TAI ^ TONG HdP MOT SO HCfP CHAT HUU CCf • • • CHUA Dl VONG PIRIDIN, THAM DO HOAT TINH KHANG KHUAN VA KHA NANG (fC CHE AN MON KIM LOAI CUA CHIJNG MA SO: QG-08-08 x^ CHU TRI DE TAI: PGS TS TRAN THACH VAN CAC CAN Bp THAM GIA: ThS TRAN THI THANH VAN TS NGUYEN VAN NGOC OAI H O C feJUOC ^ i M f^A NOI TRUNG TAM THONG TIN THU VIEN_ UKim HA NOI - 2009 MUC LUC • • I BAO CAO TOM TAT n SUMMARY -* A L C > I M D A U B PHAN NOI DUNG CHINH } TONG QVAN VE AZOMETIN VA HOP CHAT THIAZOLIDlNON-4 1.1 TONG QUAN VE AZOMETIN i.1.1 C4u true dien tir ddng phan hinh hoc, tinh baza cua azometin 1.1.2 Cac phuang phap tong hop azometin 1.1.3 Pho cua azometin: 1.2 TONG U A N V E HOP CHAT T H I A Z O L I D I N O N - : 1.2.1 Tong quan: 1.2.2 Cac phuang phap t6ng hgrp thiazolidinon-4 [17]: 1.3 U'NG DUNG CUA AZOMETIN: 1.3.1 Hoat tinh sinh hoc cua cac azometin: 1.3.2 Tinh chit Ore ch6 an mon kim loai cua cac azometin: 1.4 PHUONG PHAP NGHIEN CUU CUA DE TAI KET QUA VA Tl-JAO LUAN 2.1 TONG HOP AZOMETIN: 2.1.1 Pl|ian tich kha nang phan img ciia cac amin va andehit chua di vong piridin: 2.1.2 K6t qua tong hop azometin: 2.1.3 Ph6 h6ng ngoai ciJa azometin: 2.1.4 Pho tCr ngoai cua cac azometin: 2.1.5 Ph6 kh6i lugng cua cac azometin: 2.1.6 Pho cong huang tir proton cua cac hgp chat ( ' H - N M R ) : 2.2 TONG HOP B I S - A Z O M E T I N 2.2.1 Ket qua tong hgp bis-azometin 2.2.2 Pho hong ngoai cua bis-azometin: 2.2.3 Pho tu ngoai cua cac bis-azometin 2.2.5 Ph6 cong huong tu hat nhan'lI-NMR: 2.3 TONG HOP CAC DAN XUAT CUA THIAZOLIDIN-4-ON VA BIS-THlAZOLlDlN-4-ON 2.3.1 Tong hgp cac lhiazolidin-4-on va bis-thiazolidin-4-on: 2.3.2 Pho hong ngoai ciia thiazolidin-4-on va bis- thiazolidin-4-on 2.3.3 Pho khoi lugng ciia cac thiazolidin-4-on va bis-thiazolidin-4-on: 2.3.4 Pho cong huong tu hat nhan H-NMR ciia cac thiazolidin-4-on va bis-thiazolidin-4-on 2.4 KHU'HOA AZOMETIN 2.4.1 Khu hoa azometin 2.4.2 Pho hong ngoai 2.4.3 Plli6 cong huong tu hat nhan 'H-NMR: 2.5 HOATTJNH SINH HOC CUA CAC AZOMETIN: 2.6 KHAO SAT TINH U'C CHE AN MON THEP CT-3 CUA CAC AZOMETIN TRONG MOI TRUONG AXIT HCl 2M THUC NGHIEM 3.1 TONG HOP AMINOPIRIDIN 3.2 TONG HOP AZOMETIN; 3.3 TONG HOP CAC BIS-AZOMETIN: 3.4 TONG HOPTHIAZONLIDINON-4: 3.5 KHU'HOA AZOMETIN: 3.6 HOAT TiNH SINH HOC CUA CAC AZOMETIN: 3.7 KHAO SAT KHA N A N G U C CHE A N MON THEP CT-3 CUA CAC AZOMETIN: -/ KfynuAN TAt LIEU THAM KHAO C PHU LUC \- ^ 6 b ^ t) ^ 10 12 12 12 15 /^ 15 15 17 20 22 26 30 34 34 38 38 44 46 46 46 49 52 57 57 57 58 60 63 6S 68 68 68 68 68 68 69 ~o ^/ 73 I BAO CAO TOM T A T a Ten de tai: " Tong hap mot so hgp chdt hiru ca chira di vdng piridin, thdm dd hoat tinh khdng khudn vd khd ndng itc che dn mdn kim loai cua chung" Ma so: QG-08-08 b Chij tn de tai: PGS TS Tran Thach Van c Can bg tham gia: - ThS Tran Thi Thanh Van - TS Nguy6n Van Ngoc d Muc tieu va npi dung nghien cuu: - Muc tieu: • Tong hop duac aminopiridin • Tong hop cac azometin chua vong piridin • Chuyen hoa cac azometin thiazolidinon-4 hoac amin bac • Khao sat hoat tfnh khang khuan, khang nam va kha nang uc che an mon ciia chiing - Npi dung: • Tong quan tinh hinh nghien cuu cac chat chua vong piridin theo huang tren • Tong hgp 2-azometinpiridin va 3-azometinpiridin • Tong hgp cac azometin chua vong piridin roi nghien cij*u cau true ciia chiing Khao sat kha nang khang khuan, khang nam ma cac ca quan phoi hgp co Xht h6 trg dugc Khao sat kha nang irc che an mon kim loai ciia cac azometin • Chuyen hoa azometin thiazolidinon-4 va amin bac roi khao sat cac hoat tfnh kt tren e Ket qua dat dugc: + Ket qud khoa hpc: • Da tong hgp dugc 37 azometin va 19 bis-azometin • Tong hgp dugc 11 thiazolidinon-4-on va bis-thiazolidin-4-on tu cac azometin va bis-azometin tuong ung • Da khiY hoa dugc azometin va bis-azometin ve amin bac bang NaBH4 • Cau tao cua cac azometin, bis-azometin, thiazolidinon-4 va san pham khu hoa dugc chirng minh bang hong ngoai tu ngoai cgng huong ' H-NMR va khoi lugng • Da thir hoat tinh sinh hgc cua 43 azometin va bis-azometin • Tien har^i khao sat kha nang ire che an mon kim loai theo phuang phap ton hao khoi lugng dugc 25 mau azometin va bis-azometin + Ket qud cdng bd: Vai ket qua da cong bo cong trinh sau day: - Tran Thach Van, Tran Thi Thanh Van, Le Thi Thanh Tra, 2009 "Tong hgp nghien cuu cau tao mot so hgp chat azometin va bis-azometin chira di vong I' ' , piridin" Tap chi Hoa hoc, T.47, so 2A, tr 126-131 - Tran Thach Van, Tran Thi Thanh Van, Le Thi Thanh Tra Cao Thi Huang Chu Thi Lanh, 2009 "Tong hgp, nghien cuu cau tao va hoat tinh sinh hgc ciia mot so azometin chua di vong piridin" Tap chi Hoa hgc, T.47, so 4A tr.269-274 - Tran Thach Van, Tran Thj Thanh Van, Le Thi Thanh Tra, 2009 ''Tong hgp nghien cim cau tao va hoat tinh sinh hgc ciia mot so bis-azometin chira di vong piridin" Tap chi Hoa hgc, T.47, s5 4A, tr.778-782 • Dua tren 66 tai da gop phan dao tao dugc: Da gop phan dao tao 01 thac sy (Le Thi Thanh Tra, CH K18), 02 sinh vien K50S (Cao Thj Huang va Chu Thi Lanh) bao ve cong khoa luSn tot nghiep va 02 sinh vien K51S (Nguyen Thi Nga va Nguydn Thi Phuong) lam nghien cuu khoa hgc f Tmh hinh su dung kinh phi: Tong kinh phi dugc cap cho viec thuc hien de tai la 90 trieu dong chii yeu dugc diing de mua hoa chat thi nghiem Mot phan khac dugc dimg de thue mudn chuyen mon va lao dong Hd noi, ngdy 10 thdng 12 ndm 2009 KHOA HOA HOC CHU NHIEM DE TAI P6S-,7^t^H U^^ v'o^t^ll^' PGS TS Tran Thach Van T R l / d N G DAI HOC KHOA H O C TlT N H I E N •HO Hif u naoNe ^c.]iY^\.y&^f^'^ ^)l^^^^'^^^^ n SUMMARY a Reaserching Project: "Synthesis and investigation of anti-bacterial corrosion inhibition activity of some compounds containing pyridine ring" and metallic Code: QG 08-08 b Director: Tran Thach Van, Prof.Ph.D c Members: - Tran TIiiTlianh Van, M.S - Nguyen Van Ngoc, Ph.D d Researching Attitudes and Contents: - Researching Attitudes: • Synthesis of aminopyridine • Synthesis of some azomethines containing pyridine ring • Transform sofctie azometines into thiazolidinon-4 or amine • Investigation of anti-bacterial and metallic corrosion inhibition activity of them - Researching Contents: • Synthesis of 2-aminopyridine and 3-aminopyridine pyridinandehid • Synthesis of some azomethines containing pyridine ring then determining the constitutions of the products Investigation of anti-bacterial and metallic corrosion inhibition activity of azometines • Transform some azometines into thiazolidinon-4 or amine then investigation of antibacterial and metallic corrosion inhibition activity e Results: • 37 azometines and 19 bis-azometines have been synthesized • 11 thiazolidinon-4 and bis-thiazolidinon-4 have been synthesized • azomethines and bis-azomethines have been disposed • Tlie constitutions of the products have been determined by using IR-, UV-VIS, MS and NMR spectroscopies • Anti-bacterial of 43 azomethines and bis-azomethines have been surr\'aied • Metallic corrosion inliibition activity of 25 azomethines and bis-azomethines have been surrvaied • Three reaserching paper has been submitted • The reaserching project has contributed to the graduations of one master two baciielors and the researchs of two juniors A LCJI MO DAU Cac azometin dugc ggi la baza Schiff la nhCmg hgp chat phan tu chiia nhom lien ket azometin ~C=N- kieu R-CH^N-R', R va R' la cac g6c ankyl ar\i hoac hetaryl Nguoi ta biet den loai hgp chat tir lau song chi vai chuc nam gan da\ chiing moi dugc nghien cuu nti'ieu, nhat la tir phat hien thay chung va cac san pham chuyen hoa tir chiing CO nhieu boat tinh sinh hgc quy gia; nhu tfnh khang kliuan, cliong \icm, dicl nam \a khang virul Dac biet la tinh chat ire che an mon rat cao vai nhieu loai kim loai va hgp kim cac moi truang khac Cac azometin co kha nang phan img cao, co the tham gia vao nhieu qua trinh sinh hoa va chuyen hoa hoa hgc khac tao nhieu hgp chat c6 the umg dung dugc pham bien tinh cao su, hoa phan tich va ITnh vuc phong chong an mon va bao ve kim loai NhijTig nam gan day, nhieu cong trinh nghien cim ve azometin chira nhan tham di vong da dugc cong bo Nhung vai cac azometin chira dj vong piridin it dugc de cap den Chfnh vi \ a> de tai dat mot so nhiem vu sau: • Tong hgp cac azometin di tir 2-aminopiridin, 3-aminopiridin • Tong hgp cac bis-azometin di tir piridin-2-andehit, piridin-3-andehit va piridin-4andehit • Chuyen hoa cac azometin va bis-azometin cac dan xuat thiazolidinon-4 tuang irng • Khir hoa cac azometin va bis-azometin cac amin bac tuang img • Thii' hoat tfnh sinh hgc ciia cac azometin va bis-azometin da tong hgp dugc • Kliao sat kha nang ire che an mon kim loai ciia cac azometin va bis-azometin V B PHAN NOI DUNG CHINH TONG QUAN VE AZOMETIN v A HOP CHAT THIAZOLIDINON-4 1.1 TONG QUAN VE AZOMETIN 1.1.1 C5u true dien tu, d6ng phan hinh hoc, tinh baza cua azometin Phan tir azometin co thi t6n tai a hai dang dong phan cis (syn) va trans (anti).[25.26] R t ^ H R c is ( s y n ) ^ H trans ( a m i ) t- C.H Waren va cgng su [25] da nghien cuu cau triic cua N-benzylidenanilin, tinh dugc goc R2NC va thdy ring dang syn co gia tri goc 253^ va dang anti co gia tri 117^ Momen luang cue ciia cac phan tu la 1,57 D V.A.Izmailski va cgng sir [23] da chi rang a cac azometin tham co hai kieu he lien hgp: Su lien hgp nha cac dien tir n (lien hgp TZ-K) va su lien hgp giira cac cap dien tir khong chia se tren nguyen tir nita ciia azometin va he thong dien tir n nhan tham amin (lien hgp n-n) Chinh sir lien hgp n-Ti lam cho nhan tham amin quay mot goc nao khoi mat phang cua phan tir azometin V.I Minkin va cgng su [13] da co mot loat nhirng cong trinh nghien cuu ve tfnh dong phang cua azometin Cac tinh toan ly thuyet cho thay goc khong dong phang la 40-90', tinh toan bang phuang phap tir ngoai thi goc khong dong phang la 45-60 Nguyen tir nita ciia lien ket azometin co cap dien tir khong chia se, vay nita la trung tam baza Lewis Su lien hgp n, 71 co anh huang nhat djnh den lire baza ciia azometin, cac nhom the a nhan tham hgp phan amin co anh huang ro ret den lire baza ciia phan tir azometin, cac nhom the a nhan tham hgp phan andehit co anh huong khong dang ke den tfnli baza cua phan tir azometin Cac gia tri pKb cua cac benzylidenanilin nam khoang 9-13 De xac dinh hang s5 pKb tuang doi cua cac baza azometin, nguai ta thuong diing phuang phap chuan do the axetonitrin hay etanol-nuac (1 : 1) Cac gia tri pKb nhan dugc CO mot su tuong quan tuyen tfnh tot vai cac hang so nhom the Hammelt Thong so phan irng p ciia su tuong quan tren luon duang (p>0) chimg to su co mat ciia cac nhom the hut dien tir nhan tham se lam giam mat dien tir a tren nguyen tir nita va lam giam lire baza cua phan tir azometin va ngugc lai 1.1.2 Cac phuong phap tong hop azometin Cac azometin co the dugc tdng hgp bang cac phuang phap kliac Sau day la nhung phuang phap chinh: 1.1.2.1 Phdn ung giua andehit vd amin bac mat Day la phuang phap thuan Igi nhat de tong hgp cac azometin xuat phat tir chat dau de kiem, cho hieu suat cao Phan img nhu sau: R'-CHO +R'-NH2 -^ R'CH=NR- +H2O Trong do: R va R co the la goc ankyl, aryl hay di vong Noi chung, cac azometin beo dieu che tir andehit beo va amin beo khong ben cac azometin tham ben vung han Dac biet cac azometin tham hoan toan thi rat ben virng CO che cua phan ung giura andehit va amin bac mot dugc bieu dien bang so tong qual sau: [7] !: (1) ^ ^ * R—CH-NHj—R ^ O" R—CH-NH OH {2) R ^ > R—CH=N-R + HnO (1) Khao sat mot so lan phan ung loai bang quang nguai ta nhan thay vach hap thu ciia nhom C ^ O bien di rat nlianh, tham chi co bien het truac xuat hien vach hap thu ciia nhom C = N; dieu chimg to sinh hgp chat trung gian (I) Xuc tac cho phan ung la axit hoac baza cho ca hai giai doan tan cong nucleophin ciia amin vao nhom cacbpnyl (1) va giai doan tach nuac de tao azometin (2) Khi diing xiic tac axit, CO che phan img dien nhu sau: 1^ ^ ^ + R—NHn + I OH c > i^- R—Chf-NH -^2^ R ^ + "^^ R—ChF^Nhf-R ^ R-LCH=N-R ^oti (D Con sir dung baza lam xuc tac, ca che dien nhu sau: R-NH2 ^ + B" ^ ' R-CH^^O ^ + R-NH" - R-NH =s=^ R1_CI-HNH R'^ +B^ -^ O ^ -^ r> , R—ChH—NH-R -V OH -Ufl < ^ R—CH=N-R^ Dac trung cua phan ung la sir thay d6i ca ch§ theo sir thay d6i pH ciia phan img [13] Khi tang tinh axit, pH giam, toe tach nuac tang nhung tang ndng amin a dang proton hoa, l6c phan img cgng giam Giai doan quyet djnh toe la giai doan cgng nucleophin Klii tang gia tri pH giam tinh axit, su proton hoa hgp chdt cgng giam, giai doan tach nuac cham va tra giai doan quyet dinh toe phan img 1.1.2.2 Phdn dng khfrhod amit the [lj 0-CH3-C6H4-CO-NH-C6H5 SnCl., - ^ ^ 0-CH.-C6H4-C-N-C0H5 0-CH3-C6H4-CH-N-C6H5 (62-70%) I CI Han che cua phuong phap la viec khir hoa khong chgn lgc, dong thai cac san pham trung gian de bi thuy phan 1.1.2.3 Di tir hpp chdt azo vd metylaren Phan une dien nhu sau: ^ CH3-N=N-C6H5 + CH3-C6H5 t° cao • CfeHs-N^CH-CftHs -QH5NH3 / 1.2.4 Di tir hpp chdt tham cd nhdm metyl hoat ddng vd hcrp chdt nitrozo /—\ (H3C)2N-Hf V N O + O2N /—\ HgC-^f V N O Na2C03, t ^ O^N (HaQjN—^ ' ^ N = C H ^ ^ ^ H2O OoN 1.1.2.5 Bdng phdn Ung giUa andehit tham vd hap chdt nitro tham Phan irng ciia andehit tham va hgp chat nitro tham cacbon oxit vai sir co mat ciia hgp chat chira paladi va cac hgp chat c6 chira nita, photpho va Fe2Mo7024 cho san pham azometin Thi du hon hgp cua benzandehit, nitrobezen, phuc Cb-piridin va CO benzen a 150 atm, 230"C gia cho benzyliden vai hieu suat % [10] CftHs - CHO + C6H5NO2 ^^Q^^"^-^h C6H5CH=N-C6H5 1.1.2.6 Ngung tu cdc hpp chat nitro beo hay thorn beo cd nhdm a-metylen vai cdc nitrozoaren Phan img xay vai su co mat cua natri hidroxit hay natri xianua [19] Cf,H5CH2NO^'+ HO // NaCN \s—K\(ru^\ N(CH3)2 ^^ uH ^nC R —n C—= M N 's'-e // \s N{CH3); 70 1.1.2.7 Bdng phdn ung giCta nitroaren vd cdc a-hetarylaxetonitrin Phan img xay co mat kiem, hieu suat dat tir 50-80%) O7N ~N CH2-CN w/ + C2H5OH CH2-CH2-C1 KOH CH3 N CH3 CH=N (\ \ ^/ /)—N-f-CH2-CH2-CI ^ '2 1.1.2.8 Di td' cdc di vdng chua nita cd nhdm metyl hoat ddng vd cdc nitrozoaren Phuang phap dat hieu suat tir 50-70%) + O.N •N-(-CH2-CI-l2-OH \\ // CH=N •N-(- \\ CH2-CH2-OH j // Trong cac phuang phap tong hgp azometin da neu tren thi phuang phap di tir andehit va amin bac la thuan Igi va bien hon ca 1.1.3 Pho cua azometin: 1.1.3.1 Pho hdng ngoai cda azometin: Trong hong ngoai cua cac azometin co dinh hap thu nam vimg 1590-1690 c m ' dac trung cho dao dgng hoa tri ciia nh6m lien ket azometin Vi tri vach hap thu phu thugc vao ban chat ciia cac nhom gan vai nhom lien ket azometin Thuong thi cac azometin beo co vach vc=N nam a so song cao han cac azometin beo tham va tham Dung moi anh huong kliong dang ke den cuong va vi tri cua vach nay, nhung thay doi nhom the hut dien tir thi cucmg cua vach DC-N giam di va ngugc lai Tinh dong phang cua phan tir cung co anh huang den cuong ciia vach 1.1.3.2 Phd tir ngoai cua azometin: Pho tir ngoai CLia azometin cung phu thugc rat nhieu vao ban chat ciia cac nhom the gan vai lien ket azometin, vao tfnh dong phang ciia phan tir va vao ban chat ciia dung moi So dai hap thu CO the la 2, hoac dai theo timg day azometin, song thuong chi co tir 2-3 cue dai hap thu nam viing 210-230, 240-270 va 320-390nm, cue dai hap thu thir nam vimg 420480nm vai cuong yeu va doi xuat hien dang diem uon va dac trung cho buac nhay dien tir n-7c Cue dai hap thu a viing 240-270nm doi tach hai dai 1.1.3.3 Phd khdi luang cua cdc azometin: Pho khoi lugng ciia cac azometin thuong cho pick ion phan tir rat manh, chfnli vi vay khoi lugng la phuang phap phan tfch hieu qua nhat viec chimg minh cau triic ciia cac azometin Ngoai dua vao ty le chieu cao giira cac pick chung ta c6 the de dang tinh dugc cong thirc cgng cua azometin va ket qua la mot yeu to gop phan khdng dinh cdu triic phan tir chat da tong hgp / 1.3.4 Phd cdng hudng tir hat nhdn ^H-NMR cua cdc azometin: Pho H-NMR la phuang phap chirng minh chfnh xac nhat cau triic ciia azometin rC-n H-NMR ciia cac azometin thuong thay xuat hien tfn hieu cgng huang ndm khoang lii' 8-9 ppm, dac trung cho proton a lien ket -CH=N- Thong thuong proton cho tfn hieu a dang singlet voi cuong manh, thugc vao nhom th§ trong_phan tir azometin ma dich chuyan hoa hgc cua proton co su khac chut it 1.2 TONG QUAN VE HOP CHAT THIAZOLIDINON-4: 1.2.1 Tong quan: Thiazolidinon^ la dan xuat ciia thiazolidin co nhom (C=0) vi tri s6 Co cong thirc nhu sau: •N-H Sthiazolidinon-4 r Nhieu hgp chat di vong thiazolidinon-4 da dugc h\k d§n nho nhung hoat tinh sinh hgc da dang Su co mat cua nhom chuyin nguyen t6 N-C-S va nhom C - loai hgp chdt da quyet dinli hang loat tinh chat sinh hgc quy gia nhu gay me, gay te, kliang amip, ch6ng co gifit chong lao, chong nhiem kliuan, tdy giun va diet ndm Viec t5ng hgp va nghien ciru \h cac hgp chat mai co chira he vong thiazolidinon-4 luon dugc nhiiu nguoi quan tam \ a no giu mot \'i tri quan trgng ITnh vuc nghien ciiu vk cac hgp chdt di vong Dia ban tien hanh nghien cuu Phong long hgp Huu co, Khoa hda hpc, trudng Dai hpc KHTN-DHQG Ha npi Muc tieu cua de tai • Tdng hgp dugc aminopiridin va piridinandehit • Tong hgp cac azometin chua vdng piridin • Chuyen hda cac azometin lhiazolidinon-4 hoac amin bac • Khao sat hoat tfnh khang khuan, khang nam va kha nang uc che an mdn ciia chung 10 Tom tdt noi dung nghien cihi cua de tai • Tong quan tinh hinh nghien cuu cac chat chua vdng piridin theo hudng tren • Tong hgp 2-aminopiridin va 3-aminopiridin • Tong hgp piridinandehit • Tong hgp cac azometin chua vdng piridin roi nghien cuu cau true ciJa chung Khao sat kha nang khang khuan, khang nam ma cac co quan phoi hgp cd the' hd trg dugc Khao sat kha nang uc che an mdn kim loai cua cac azometin • Chuyen hda azometin thiazolidinon-4 va amin bac roi khao sat cac boat tinh ke tren 11 Cac chuyen de nghien cuu du kien cua de tai • Tdng hgp amin bac • Tdng hgp andehit di vdng tham • Tong hgp va chuyen hda azomelin • Mdi lien quan giua cau true va boat linh sinh hpc 12 Cau true du kien bao cao ket qua cua de tai • Bao cao ldm tat bang tieng Viet va tieng Anh • Bao cao khoa hpc: Chuang 1: Tong quan \'6 tmh hinh nghien curu Tinh cap thiet va diem mdi ciia 66 lai Chuang 2: Cac qui trinh va phuang phap thuc nghiem Chuang 3: Cac ket qua thuc nghiem Chuong 4: Ket luan va kien nghi Tai lieu tham khao 13 Tinh da nganh va lien nganh cua de tai Di tai la su ket hgp cac linh vuc hda hiju co, hda li, hda sinh va moi trudng dugc bi^u bien nhu sau: Ndi dung ciia d^ tai gom cac phdn: • Tong hgp biJu ca nhdm tong hgp bfru ca thuc hien • Nghien cuu cau triic cac hgp chat nhdm cac phuang phap quang phd thuc hien • Khao sat kha nang khang khuan, khang nam phan sinh hda thuc hien (Trudng DH Dugc, Benh vien 19-8 Bd Cdng an) • Khao sat kha nang irc che an mdn Vien Nhiet ddi Viel-Nga, nhdm nghien cuu an mdn kim loai (Bp mdn Hda Ly, Khoa Hda hpc, Trudng DHKHTN) thuc hien 14 Phuong phap luan va phuomg phap khoa hoc sir dung de tai • Dung phuang phap long hgp amin bac (dac biet la thoai bien Hoffmann) de long hgp 3-aminopiridin di tii Nicotinamil • Dung phuang phap ket linh lai, sac ky ban mdng de tinh che san pham • Diing cac phuang phap IR, MS de xac dinh ca'u triic • Dung phuang phap dudng kihh vd khuan de xac dinh boat linh khang khuan • Diing phuang phap long tra va phuang phap khdi lugng de khao sat kha nang uc che an mdn kim loai 15 Kha nang ung dung co so vat chat, trang thiet bi cua Dai hoc Qudc gia: • Phdng thi nghiem long hgp huu co, Khoa Hda, Trudng Dai hpc Khoa hpc Tu nhien • Phdng thi nghiem Hda vat lieu (IR, UV-VIS, MS ) 16 Kha nang hgp tac qudc te 17 Cac boat dong nghien cuu cua de tai • Nghien ciiru If thuyet S • Di^u tra khao sat D • Xay diJTig mo hinh lhu nghiem Kl • Bien soan lai lieu D • Viet bao cao khoa hpc K • Hoi thao khoa hpc S • Hoat dons kliac Kl 18 Ket qua du kien • Sdn phdm khoa hoc: Tong hgp 3-aminopiridin ; 2-aminopiridin ; piridin andehit va khoang 10 den 20 azometin chua vdng piridin Chuyen hda cac azometin cac dan xuat thiazolidinon-4 va huang khac, du kien khoang 20 chat dan xua't Khao sal kha nang uc che an mdn ddng, thep CT-3 va kha nang khiing khuan ciia chiing Cac ket qua cd ihi cong bd dugc bai bao tren cac tap chf nude • Sdn phdm cong nghe: Cac chat cd boat tfnh cao nhat cd thi dugc chuyen giao cho CO quan thfch hgp de nghien cuu kha nang ling dung thuc te • Sdn phdm ddo tao: Dao lao cir nhan Cd lh6 buac dau tham dd kha nang dao tao thac sT 19 Noi dung va tien thuc hien cua de tai Thai han thuc hien STT San pham khoa hoc Hoat dong nghien cuu Tir thang Den thang Thu thap va viet l6ng quan lai lieu 01/2008 02/2008 Bao cao tdng quan Xay dung de cucmg nghien cuu chi tiet 02/2008 03/2008 Di cuong nghien cuu Tdng hgp aminopiridin 04/2008 06/2008 Bao cao chuyen de Tdng hgp mpt sd azomelin ciia aminopiridin vdi cac benzadebil 06/2008 08/2008 Bao cao chuyen de Khao sal kha nang khang khuan va lie che an mdn cua azometin 08/2008 10/2008 Bao cao chuyen di Hdi thao Chuyen hda azometin 12/2008 06/2009 Bao cao chuyen dd Khao sat hoat tfnh CLia san pham 06/2008 08/2009 Bao cao chuyen di Viet bao cao chuyen de 08/2008 09/2009 Bao cao 10 Hoi thao lan cuoi va hoan thien bao cao 09/2008 10/2009 Bao cao tdng ket 11 Nop san pham va nghiem lhu di lai 10/2008 12/2009 11/2008 Ki yeu 20 Phan bo kinh phi Dan vi tfnh: trieu dong Kinh phi Npi dung STT Nam thu 1 Nghien cuti khoa hoc 1.1 Thu thap va viet tdng quan tai lieu 2,0 1.2 Xay dung de cuang chi tiet 1,0 1.3 Tong hgp aminopiridin 7,0 1.4 Tdng hgp azometin 7,0 1.5 Khao sat kha nang uc che an mdn, boat tfnh khang khuan 1.6 Chuyen hda azometin 1.7 Khao sal boat tinh ciia san pham chuyen hda II Chi mua s3m trang thiet bi, nguyen vat lieu 2.1 Mua hda chat HI Viet bao cao khoa hoc nghiem thu 3.1 Viet bao cao 3.2 Hoi thao 3.3 Nghiem lhu VI Chi khac V Nam thirl 10,0 7,0 10,0 10,0 20,0 4,0 1,0 1,0 3,0 Mua van phdng pham 0,5 In a'n, pholocopi 1,6 Quan ll phf 2,5 Thii lao chii tri d^ tai 2,4 25,0 65,0 Tong kinh phi Tong cong 90,0 TAI LIEU THAM KHAO Giang Thi San va nhung ngudi khac Nghien cuu tdng hgp va tac dung sinh hpc cua azometin Tuyen tap cac cong trinh Hdi nghi Khoa hpc va Cong nghe Hda hiJu ca loan qudc lan thii: hai, trang 81-88 (2001) S L Li H Y Ma, S B Lei, R Yu and S H Chen Corrosion, 54, No 12, 12 (1998) Ngay^k thdng{^ndm NgdyO) thdngi^ndm 2007 2007 Chu tri de tai Phd Chu nhiem Khoa Hda hoc PGS TS Tran Thach Van PGS TS Tran Thi Nhu Mai Ngdy iO thdng \z ndm 2007 Ngdy thdng i Lndm 2007 Xac nhan cua trudng DHKHTN Phe duyet cua DHQGHN TL Giam ddc DHQG HN V ^Jxitgng Ban KHCN o re-i ^ G S TS o^ii^JA^^iz^n- TSKH Nguyen Dinh Due Dai hoc Quoc gia Ha ndi Trudng Oai hoc Khoa hoc Tir nhien KHOA HOA HOC-BO MON HOA HOC HUU CO PHIEU DANG Ki Hl/CING D A N SAU DAI HOC TRONG CAC DE TAI KHOA HOC CONG NGHE I Ten de tai luan van thac sT De tai 1: Nghien cuu tong hgp, chuyen hda va khao sal kha nang uc che an mdn kim loai ciia cac hgp chat azomelin di lir aminopiridin Di tai 2: Nghien cuu long hgp, chuyen hda va khao sal kha nang uc che an mdn kim loai ciia cac hgp chat azomelin di lu piridinandehit II Can bo hudng dan: PGS TS Tran Thach Van III Cao hoc vien IV Noi dung chinh cua luan van: Tdng hgp cac cha't dau [aminopirridin {di tai 1); piridinandehit (de tai 2)] Tdng hgp cac azometin lir cac amin va andehit da tong hgp dugc Chuyen hda cac azometin tbiazolidinon-4 hoac khir amin bac hoac p-amino este theo phan litig reformatsky Khao sal kha nang khang khuan, khang nam, uc che an mdn kim loai V Dieu kien thuc hien - Sir diing thiet bi hien co cua Trudng DHKHTN-Khoa Hda - Phoi hgp vdi Trudng DH Dugc Ha ndi va Benh vien 19-8 Bp Cdng an VI Du kien kinh phi danh cho luan van: 60 trieu dong Xac nhan ciia Khoa Hda hoc fC',Sli Iv^l t u N>^'^^^M Ha ndi, ^ thang 1^ nam 2007 Ngudi dang ki PGS TS Tran Thach Van Xac nhan cua Phdng dao tao Sau dai hoc fl^J^SXjl'Ll T/.j.nfi DAI HOC QUOC GIA HA NOI anh 4x6 LY LICH KHOA HOC (Ddnh cho cdc cdn bg ddng ky chu iri vd tham gia thuc hien cdc de tdi KHCN cua DHQGHN) THONG TIN CA NHAN Ho va ten: TRAN THACH VAN Nam sinh: 1951 Nam Noi sinh: Thach San-Lam Thao- Phii Tho Nguyen quan : Phii Thp Dia chi thuong tru hien nay; Phudng: NghTa Dp Quan: C^u Gia'y Thanh phd: Ha noi Dien thoai: NR 04 8360755 Mobile: 0979780866 E-mail: Hoc vi: Tien sT Nam bao ve: 1985 Noi bao ve: Khoa Hda hpc - DH Tong hgp Ha npi Nganh: Hda hpc Chuyen nganh: Tong hgp hiJu co Chuc danh khoa hoc: Phd giao su Noi phong : DHQG HN Nam phong: 2002 Chiirc danh nghien cuu: Giang vien chinh 10 Churc vu: II Co quan cong tac: Ten CO quan: Trudng Dai hpc KHTN- DHQG Ha ndi Phdng TN, Bp mdn, Khoa: Phdng Tong hgp biiu ca, Bd mdn Hda Huu co, Khoa Hda hpc Dia chi co quan: 19 Le Thanh Tong Ha npi Dien thoai: 04 8533503 TRINH DO HOC VAN 12 Qua trinh dao tao Chuyen mdn Noi dao lao Bac dao tao Hda huu ca DHTH Gdansk-Balan Dai hoc Hda hijTj c a DH Tdng hap Ha ndi Tien sT 13 Cac khoa dao tao khac 14 Trinh dd ngoai nsu Trinh dd C Trinh dd B TY Ngoai ngu Trinh dd A X Tiene Balan x Tieng Anh 11 Nam tdi nghiep 1975 1985 Chung chi qudc le KINH NGHlfiM LAM VIEC VA THANH TICH KHCN 15 Qua trinh cong tac Thdi gian Vi trf cong tac Ca quan cdng lac Dja chi caquan (Tir nam., den nam ) 8-1975 den Can bd giang day DHKHTN-DHOG HN 19 Le Thanh Tdng 16 Cac bai bao khoa hoc 16.2.1 Sd bai bao dang tren tap chf nude ngoai: 02 16.2.2 Sd bai bao dang tren tap chf nude: 14 16.2.3 So bao cao tham gia cac Hdi nghi khoa hpc Qudc te 16.2.4 Sd bao cao tham gia cac Hoi nghi khoa hpc nude: 02 16.2.5 Li6t ke ddy dii cac bai bao theo thu tu thdi gian: TT Ten bai bao La tac gia hoac Ten tap chi Nam dong tac gia cong bo cdng bd I Dong tac gia Synthesis of y-tetrazole analogues of Tetrahedron 1977 L-glutamic acid and its derivatives Tdng hgp mpt so baza azomelin va Dong lac gia Tap chf Hda 1982 thiazolidinon- cd chua ddng thdi di hpc vdng furan va thiazol Tong hgp mpt so azometin va Dong tac gia Tap chf Hda 1982 thiazolidinon-4 chua dong thdi di vdng hpc thiophen va thiazol Tong hgp mot so' dSn xuat ciia 5,6Dong tac gia Tap chf Hda 1984 benzoquinolin cbira he vdng arylfuran hoc Gdp phdn nghien cuu ca che phan ung Ddng tac gia Tap chf Hda 1985 giua axit thioglicolic vdi baza azometin hoc Tong hgp mot so thiazolidinon- chua Ddng tac gia Tap chf Hda 1986 he vdng arylfuran va benzothiazol hoac hpc naphtalen Dong tac gia Tong hgp mot sd azometin day 2Tap chf Hda 1987 amino- 4- arylthiazol hoc Tong hgp va nghien ciiu hoat tfnh khang Dong tac gia Tap chf Hda 1987 khuan mpt sd din xuat thiazolidinon-4 hpc va 5,6- benzoquinolin cd chua vdng arylfuran Dong tac gia Pho dien iir ciia cac azomelin day Tap chi khoa 1987 4- phenyl, 4-p-Tolyl- va 4-p-Clophenylhoc trudng 2-aminothiazol DHTH HN Dong tac gia 10 Reactivation of vanadium Biochimica et 1991 bromoperoxidase; inhibilation by Biophysica metallo-fluoric compounds Acta 11 The synthesis of thiazolo[4,5-n and Ddng tac gia j Hpi nghi Hoa 1993 thiadiazolo[4,5-f Iquinoline- 4hpc loan qudc cacboxylic acid ' lan thu 11 Tac gia 12 Tong hgp mpt sd azomelin day 5Thdng bao KH 1996 aminobenzothiazol va 5- amino ciia cac trudng benzothiadiazol Dai hoc i 12 13 14 15 16 17 18 Tong hgp va danh gia kha nang uc che an mdn kim loai ciia 2'-aminothiazolo( \ ' : 5,6)-quinolin Tong hgp mot sd' azometin day 2metyI-5- aminobenzothiazol Tdng hgp mot sd dan xual cua tetrazol Quan he giSa cau triic vdi kha nang lie che an mdn kim loai ciia 2'-amino thiazolo-(5\4': 5,6)-quinolin Tong hgp va khao sat kha nang uc che an mdn kim loai cua cac baza schiff chua nhan benzothiazol, benzothiadiazol va indol Tong hgp mot so' azometin cCia 5-amino1,2-dimelylindol Dong tac gia Tap chf HH va cdng nghiep hda chat 1997 Dong tac gia Tap chf Hda hoc Tap chf HH va CN hda chat Tap chi khoa hoc DHQG HN Tuy6n tap cac cdng trinh KH Hdi nghi KH lan lhu bai Tap chf Hda hoc 1998 Tac gia Ddng lac gia Dong tac gia Ddng lac gia 1998 1998 2000 2001 17 De tai, du an, nhiem vu KHCN cac cap da chu tri hoac tham gia 17.1 Di tai, du an, nhiem vu KHCN cac cap da va dang chii Iri Thdi gian (bat Caquan quan ly Tmh trang di tai Ten/cap dau-ke'l Ihiic) Trudng DH Da nghiem lhu Nghien cuu long hgp va lac dung uc che 1999-2000 Tong hgp HN an mdn dong cQa baza azometin chiia vdng benzothiazol Cap DHQG HN Da nghiem lhu 2001-2003 Nghien cuu kha nang uc che an mdn kim loai cua mpt so hgp chat chua vdng thiazol 17.2 De tai, du an, nhiem vu KHCN cac cap da va dang i\lam gia vdi tu each vien Thdi gian (bat Ca quan quan ly Tinh trang di tai Ten/ca'p dau-ke'l ihiic) Cap Bp Cdng Da nghiem lhu 1992 Nghien cuu qui irlnh long hgp cac chat nghiep nhe mau thuc pham sunset yellow FCF va tartrazine Cap nha nude Da nghiem thu 1990-1995 Xay dung qui trinh cdng nghe tach chiet, long hap cac chat mau thuc pham (KihieuKC.06 08) Cap nha nude Da nghiem thu 1993 Tong hgp, nghien cuu cau iriic, co che phan ung va tham dd kha nang ung dung ciia mpt sd hgp chat di vdng nita (Kihieu KT.04.416) Cap nha nude Da nghiem lhu 1996 Nghien cuu long hgp cac hgp chat di vdng cd hoat linh sinh hpc (Ki hieu KT.04.4.1.41) Cap nha nude Da nghiem thu 1997 Tdng hgp nhung hgp chat c6 boat tinh sinh hoc (Ki hieu 5.4.2) Cap nha nude Da nghiem thu 1998-2006 Tong hgp va chuyen hda mpt sd : ^ azometin di vdng Di tai NCCB 13 1 ' 1 18 Qua trinh tham gia dao tao SDH 18.1 So lugng tien sTda dao tao: 01 18.2 Thong tin chi tiet: Vai trd hudng dan Ten NCS Ten luan an ciia NCS Phu Nguyin Van Ngpc Nghien cuu tong hgp va timg dung mpt so hgp cha't di vdng chiia nita Ca quan cdng lac Vien nhiet ddi Viet-Nga Ngayl/t| thang jL nam 2007 XAC NHAN CUA THU TRUONG DON VI Ngudi khai PGS TS Tran Thach Van •v.- * T I; S ^ 'f^i f^un^ 14 'C^^i - / * W DAI HOC QU6C GIA HA N O I LY LICH KHOA HOC (Ddnh cho cdc cdn bp ddng ky chu tri vd tham gia thuc hien cdc de tdi KHCN cua DHQGHN) THONG TIN CA NHAN Ho va ten: TRAN THI THANH VAN Nam sinh: 1977 Nu Noi sinh: Thach San-Lam Thao- Phii Tho Nguyen quan : Phii Thp Dia chi thudng tru hien nay: Phudng: NghTa Dp Quan: Cau Gia'y Thanh pho: Ha ndi Mobile: 0989141695 Dien thoai: NR 04 7537624 E-mail: tvche@yahoo.com Hoc vj: Thac si Nam bao ve: 2003 Noi bao ve: Khoa Hda hpc Dai hpc Khoa hpc Tu nhien-t)HQG Ha npi Chuyen nganh: Tong hgp huu co Nganh: Hda hpc Chuc danh khoa hoc: Chuc danh nghien cuu: Giang vien 10 Chuc vu: Phd chii nhiem Bd mdn Hda huu co 11 Co quan cdng tac: Ten CO quan: Trudng Dai hpc KHTN- DHQG Ha npi Phdng TN, Bd mon, Khoa: Phdng Tong hgp hiju ca, Bp mon Hda Huu co, Khoa Hda hoc Dia chi ca quan: 19 Le Thanh Tdng Ha npi Dien thoai: 04 8533503 TRINH DO HOC VAN 12 Qua trinh d ao tao Chuyen mdn Nai dao lao Bac dao tao Hda huu ca Dai hpc Khoa hpc Tu Dai hpc nhien-DHOG Ha ndi Hda huu ca Dai hpc Khoa hpc Tu Thac sT nhien-DHQG Ha noi 13 Cac khoa dao tao khac 14 Trinh neoai neu Trinh B Trinh C TY Ngoai ngu Trinh A X Tieng Anh 15 Nam lot nghiep 1999 2003 Chung chi quoc Le 1 KINH NGHIEM LAM VIEC VA THANH TICH KHCN 15 Qua trinh cong tac Thai gian Vi tri cdng tac Ca quan cdng tac Dia chi caquan (TlT nam., den nam ) Tir 2000 den Can bp giang day DHKHTN-DHQG HN 19 Le Thanh Tdng 16 Cac bai bao khoa hpc 16.2.1 So' bai bao dang tren tap chi nude ngoai: 16.2.2 Sd bai bao dang tren tap chi nude: 04 16.2.3 Sd bao cao tham gia cac Hpi nghi khoa hpc Qudc le: 16.2.4 So bao cao tham gia cac Hpi nghi khoa hpc nude: 05 16.2.5 Liet ke ddy dii cac bai bao theo thir tu thdi gian: La tac gia/ Ten tap chi cong Nam Ten bai bao TT dong tac gia cdng bd bo Tdng hgp, xac dinh cau tao va thu boat Dong tac gia Tuyen tap cdng 2000 tfnh sinh hpc ciia mpt sd dan xuat 5trinh Hpi nghi aryl-2-mecaplo-1,3,4-oxadiazon, khoa hpc Trudng Dai hpc Khoa hoc Tu nhien Dong lac gia Tuyen lap cdng Pho hdng ngoai ciia mpt sd fomazan 2000 chiia di vdng quinolin irinh Hpi nghi khoa hpc Trudng Dai hpc Khoa hoc Tu nhien Tong hgp, xac dinh cau triic va thir boat Dong lac gia Tuyen tap cac 2001 tfnh sinh hpc ciia mpt sd dan xuat the d cdng trinh Hdi vi trf sd ciia 2-amino-1,3,4-lhiadiazol nghi Hda hpc va va l,2-diamino-l,3,4-triazoI Cdng nghe Hda Huu ca loan qudc Tong hgp, nghien ciiu cau tao va su tao Ddng tac gia Tuye'n lap cac 2003 phuc CLia mpt sd dan xuat fomazan cd bao cao tai Hoi kha nang lan nude nghi Hda hpc loan qudc lan thu tu Ddng lac gia Nghien cuu long hgp mot so fomazan Tap chf Khoa 2004 chiia di vdng pirol, tong hgp phuc cua hpc, Dai hpc fomazan chiia di vdng pirol va 4,5Qudc gia Ha noi dimetyl thiazolyl fomazan vdi mot sd ion kim loai chuyen tiep Tinh loan hang sd bin cua phuc Ddng tac gia Tap chf Phan lich 2005 fomazan chua di vdng vdi mpt sd ion Ly-Hda-Sinh kim loai chuven tiep Ddng tac gia Tap chi Hoa hoc Tong hop va nghien cihi cau lao mot sd 2005 hgp chat fomazan chiia di vdng furan, thiophen va pirol Dong tac gia Tuy^n lap cac Nghien cuu tdng hap mpt sd difomazan 2005 cdng trinh Hoi chua di vdng nghi khoa hoc va 16 Tong hgp, xac dinh cau tao va ihtr boat tfnh sinh hpc ciia mpt sd din xua't ciia axit aryl acrylic Dong tac gia cdng nghe hda biiu CO Tap chf Hda hpc va litig dung 2006 17 De tai, d u an, nhiem vu KHCN cac cap da chu tri hoac tham gia 17.1 Di tai, du an, nhiem vu KHCN cac ca'p da va dang chii tri Ten/ca'p Thdi gian (bat Co quan quan ly dau-ket thiic) Tong hgp mot sd phuc ran ciia fomazan 2004-2005 Trudng Dai hoc KHTN-DHQG chiia di vdng thiophen, pirol, furan va Ha ndi thiazol vdi ion kim loai chuyen tiep Dai hpc Qudc 2005-2006 Tong hgp mpt so hgp chat hiru co cd gia Ha ndi hoat ifnh sinh hoc 17.2 Di tai, du an, nhiem vu KHCN cac cap da va dang tham gia vdi lu each Thdi gian (bat Ca quan quan ly Ten/cap dau-ket thiic) Cap Nha nude 2005-2007 Nghien cuu long hgp Zidovudin mpt loai thudc chdng HIV-AIDS cd hieu qua hien Tmh trang de lai Da nghiem thu Da nghiem lhu vien Tmh trang d^ Iai Chua nghiem thu 18 Qua trinh tham gia dao tao SDH 18.1 Sd lugng tien si da dao tao: 18.2 Thdng tin chi tiet: Ngay 15 thang 07 nam 2007 Nguoi khai XAC NHAN CIJA THU TRUONG DON VI ThS Tran Thi Thanb Van u*^ 17 PHIEU DANG KY f: KET QUA NGHIEN CLfU K H C N Ten de tai (hoac du an): " Tong hap mot sd hap chdt hihi ca chira di vdng piridin^ thdm dd hoat tinh khdng khudn vd khd ndng ice che an mon kim loai cua chung " Ma so: QG- 08-08 Co quan chu tri de tai (hoac du an): Khoa Hda-Trudng DHKHTN Dia chi: 19 Le Thanh Tdng Ha ndi Tel: 04 38 533 503 Co quan quan ly de tai (hoac du an): Trudng Dai hpc Khoa hpc Tu nhien Dia chi: 334 Nguyen Trai- Thanh Xuan-Ha ndi Tel: 38584287 Tong kinh phi thuc chi: 90 000 000 ddng (Chin muoi trieu dong) Trong dd: - Tu ngan sach Nha nude: - Kinh phi cua trudng: 90 000 000 dong - Vay tin dung: - Vdn tucd: -Thu hoi: Thoi gian nghien cuu: 24 thang Thoi gian bat dau: 1/2008 Thoi gian ket thiic^ 12/2009 Ten cac can bp phdi hpp nghien cuu: So dang ky de tai: QG 08.08 - TliS Tran Thi Thanh Van - TS Nguyen Van Ngpc Sd chung nhan dang ky ket qua nghien cuu: Bao mat: a Pho bien rong rai: b Pho bien han che: D Ngay; c Bao mfit: LJ Tom tdt ket qua nghien cuu: Ket qua tdng hap: Da long hop duoc cac chat chira dj \ong piridin gdm 56 hgp chal azomelin 15 thiazolidinon-4-on 11 amin bac hai Cku tao cua chiing dugc khang dinh nhd cac phuang phap vat ly nhu phd hdng ngoai, tu ngoai, phd cdng hudng 'H-NMR va phd khdi lugng Kit qud thd'hoat tinh sinh hpc: 43 hgp chat azometin cd boat tinh khang vi khuan Gram (-), Gram (+) va nam men Albican d ndng dp 150|ag/l Ket qud thu khd ndng uc die dn mon: Cac azometin deu cd kha nang lie che an mdn ddi vdi thep CT-3 mdi trudng axit HCl 2M Kha nang chdng an mdn cua azometin cao hon rat nhieu so vdi cac andehit va amin phan Khd ndng ung dung: Trong sd cac azometin thi chat Til la: Vua cd cau tao don gian, vua cd kha nang bao ve kim loai tdt nhat nen cd the nghien ei^i'u chi tiet them nham miic dich sir dung thuc te Kien nghi ve quy md va ddi tugng ap dung nghien cuu: Chu nhiem de tai Thu trudng ca quan chii tri de tai Chii tich Hpi dong danh gia chinh thuc Thu tru