Bai 1: Diéu ché NaCl A. Cau hi dau gid: Pp tinh ché trong bai nay la gi? Nhuge diém ciia pp nay? Pp tinh ché sd trong bai nay la két tinh = pp c6 can, Nhurge diém cita pp nay: tén thé gian, kh6 ap dung cho nhiing dung mdi khé bay hoi, hay nhing hop chat kém é hgp chat thu duoc khdng tinh khiét. Dé ngoai kk mudi bj oxh va chay nudc, mudi duge dung da loai hét cdc ion KL kiém thé nén ko bi chay Mau sac céc chi thi? rung tinh hoa ma ko mt kiém hay a ? Vi day la dd tiém truyén nén phai trung tinh hoa dé Tai sao khong duge dun dén s6i cua gian dogn 2a? Vi khi dun dén s6i mudi NaCl sé két tinh lai va bj loai bé khi Igc Lam giam higu suat. 6 gian doan nay chi can dun nhe dé tia carbonat kiém thé hoan toan va logi b6 ching khi loc. Tai sao ko dun dén can kh6? Tai sao phai nén chat mudi trong phéu x nude cé nhiéu Br- ‘Néu c6 can qué thi sé ko dat tc gi khi kiém nghigm? anion I’ va cation Ca* Ko dun dén can dé logi cdc tap [a ion tan trong nude nhur I, Br’, K°. (vi giai doan sau rira = nude lanh) Cho biét pH cia dd khi diéu chinh = 2 chi thi khoan bao nhiéu? Tai sao ion COs” khi dun néng thi CO2 sé bay hoi kim pH tang lén nén thém HCI dé dd tro vé trung tinh. Cho biét nguyén tc loai KL kiém thé va nhimg lw ¥ khi thye hign? KL thé de logi bé duéi dang tia Carbonat, Giai doan tiia ktra = ech dun néng 6 60°C KL kiém thé dé két tinh > dé loai tap. Ko duge dun s6i > mat sin phim > gidm higu suit, Nude béc hoi kim NaCl két tinh cing vi nhiig mudi KL kiém thé > mat higu sudt. Khong ding K2CO3 thay thé cho Na2CO3 str dung mét chi chi xanh bromthymol cé de k ? ko vi khoang di mau cia xanh brométhyml nam trong vung pH kiém 7,6 dén 6 nén néu khi trung tinh héa dd c6 du acid né k phat hién de sd methy da cam truoc e6 de k? ko vi dd dang 0 pH kiém Khi cho Na2CO3vio dé tao ta o buée2. Vung chuyen mau cua methy da cam 3 den 4,4 nén né k phat hien de ‘Tai sao phai thir véi 2 chi thi? ~ Xanh bromothymol ddi mau ving sang xanh 6 pH 6 -> 7,6. Methyl da cam d6i mau tir d6 sang ving cam 6 pH 3,1 > 4. Néu chi diing xanh bromothymol thi khi thira acid s& khdng phat hign duge, vi chi thi di mau 6 pH kiém. Néu chi ding methyl da cam thi khi thira kigm sé khdng phat hign duge, vi chi thj d6i mau 6 pH acid. Ma digu ché NaCl thye hién 6 pH trung tinh, Vi khi trung hia = HCI dé tao thanh dd c6 pH khodn 4,4-6 nén khi diing 2 chi thj dé tranh acid qua hay base qua. Hign tugng san pham bj chay nude sau khi say? Do qua trinh Igc chwra hét mude & réo hét nude. Do qué trinh Igc chwa loai hét tap, CaCI2 chay nude. Do thém NaxCOs chua dit Khi nao mudi duge dung ko dat gidi han Ca”’, Mg” Do thém NagCO3 chu dit ‘Tap lan qué nhiéu trong mudi C6 2 pp két tinh la c6 can va két tinh Iai, ~dé cho hét nuée, vi trongBai 2 TT Héa Duge: Kiém dinh NaCl B. Cfu hdi dau giv: 4. Luu ¥ gi khi thy hign dinh tinh NaCl? tra Idi: phai dim bao dd dinh tinh de acid héa, tia xudt hign phai tan trong amoniae du. 2. Viét cdc pt gidi thich qui trinh dinh Iugng NaCl, cho biét tén phuong phap dinh lugng? tra Idi: phurong phip Mohr, dinh long trye tiép = phuong phap két tiia phurong trinh pu: NaCl + AgNO3 --> NaNO3 + AgCl két tia tai diém tong duong: AgNO3 + K2Cr204 --> 2KNO3 + Ag2Cr204 két tha d6 gach C. Cau héi miéng: 1. Giai thich 6 dau ta e6 s6 0,01% tinh theo Ca (sich trang 30) tra ldi: theo thye nghiém va qui dinh cia DDVN IV, hodc ta c6 thé tinh tir s6 2,5 ml chuan 6 ra. 2. Tai sao phai thém Kém sulfat 0,1M khi tién hinh thir gidi han tap chat Mg va cdc kim loai kkiém tho? tra Idi: 1. Thir d6 mhay cita chi thi 2. Loai cdc ion khaée gay sai s6 DL true khi cho dd cin DL vio kim. 3. Phan dinh lwong: Tai sao Ky Sml dd vira pha dé DL ma ko ly lun SOml trong BDM ban dau? tra ldi: 1. trong phong TN ko cé dung cy dit lén dé tién hanh dinh lrgng | lan hét SOml. 2. Dé ton kém vi Ag dic tién. 4. Néu han ché cua pp DL nay’ tra Idi: chi tién hinh de 6 méi trudng pH trung tinh, va ko lim duge néu 6 lin ede tap thuge nhém Halogen khic Clo.Bai 3: Tong hgp Aspirin A. Cfu hoi dau gid: 1. Néu cho du H2SO4 thi sé anh huéng ntn dén diéu ché? tra léi: Néu cho du H2S04 --> sé cé nhiéu H+ trong méi trang --> canh tranh pu voi Carbon C+ cua anhydrid acetic --> giam higu sudt pu. (c6 thé tra google or wiki dé xem dang lién hop cia acid anhydrid acetic va vi tri C+ ca 6). 2. Néu cho dur acid anhydrid acetic thi sé anh huéng ntn dén diéu ché? tra léi: sin phim diéu ché Aspirin tan trong acid anhydrid acetic dur, nén sé ko thé két tinh khi thém nue --> ko thu de sn phim. B. CAu héi migng: 1. Vai tré cia a. H2SO4 la gi’? - la chat xite tée 2. Thay acid anhydrid acetic = a. acetic thi c6 de ko? ko de, vi OH gan chat trén phenol (cia a.salicylic) nén khé tn céng vao gée C+ ciia a. acetic, muén pu dé xy ra hon thi phai c6 thém | nhém hit dién tir nita dé C+ tro nén duong hon - ~> nén ko thé thay... 3. Néu ko biét time dun la 30' thi kim ntn dé biét khi nao nén dig dun? dén khi pu xay ra hoan toan. Nhn biét = thye nghiém ding pp séc ky lép mong 6 ting thoi dén khi, xudt hién 1 chat méi va acid salicylic khéng con nita. 4. bude tiép theo, cho nude cit vao dé kim gi’ Joai tap tan trong nude: a. acetic, a. anhydrid, a. H2SO4. két tinh Aspirin. Luu y: lam cang nhanh cang tét, tranh aspirin bi thay phan. giai doan tigp theo, hoa tan tré Igi cdn ggi la gi? giai doan tinh khiét ha, tinh ché. dung pp gi dé tinh ché? pp két tinh lai. 7. tai sao sit dung dm két tinh Iai la c6n- nude ti Ig 1:4? viG ti lé nay, Aspirin sé tan 6 nhigt 46 cao (60 46) va két tinh lai 6 nhiét d6 thap durge Aspirin tinh khiét 8, Tai sao ta hoa tan Aspirin trude trong edn, ri cho thém muse 60 46 ma ko kim edch khée: cho aspirin vio hdn hgp edn + nue & 60 462 Néu lim theo cach 2 thi khi dun néng hén hop cén nude thi cdn cé thé bj bay hoi | phan true khi cho Aspirin vio, vi khi cho vao thi Aspirin c6 thé bj thiy phan boi nude 6 nhigt dO cao. Luu J: luén chuan bj sin bude tiép theo khi lam bai nay do Aspirin rat dé bj thay phan. > thuBai Kiém dinh Aspirin A. Cau hoi dau gid: 1. Khi thir gidi han -ylic nén lam 6ng chuiin true hay dng thir tre? Tai sao? > Tra li: Nén lam dng chuan trude, vi dé lau aspirin bj thay phan gay sai sé khi kiém nghigm gigi han acid salicylic. oO. oH Ox OH Or ne acetylonlicylic ecid water salicylic acid acetic acid aspitn) 2. Cp nhit sau B. Cau héi miéng: 1. Phan tng dinh tinh A dé xc dinh phan gi cia acid acetyl salicylic? > Tra loi: xae dinh nhém-COOH cia aspirin, aspirin sau khi bj thy phan thanh acid salicylic, nhém—COOH va -OH sé pu véi FeCl; cho dd cé mau tim COOH c CL + Fecl, —> cL Fe + 3HCl ‘OH 9 H 3 salicylic acid complex helat salt (violet color) 2. Phan img djnh tinh B dé xac djnh phan gi ciia acid acetyl salicylic? >_ Tra loi: nhom acetyl f drug with formation calcium salicylate and acetate calcium: 2 of “| ce + ccxycooy,ce + 24,0ve vi & Khi pha dd A, Néu aspirin tan hoan toan thi dd thu de bao nhiéu %? C6 miy loai nong d6 %? Khi cfn 2g ta cin chinh xac hay chinh xac khoan? Tai sao? 2 . o Tra lois for = 4% (g/m). C6 3 loai ndng d6 %: kVKI, kUtt, tt © Cfn chinh xc vi sau khi can ta pha vao binh dinh mite ¢6 thé tich xe din SOml ii sao phai dé ngudi rdi loc? joa tan dd A, loc dé thu de gi? 1 Tra lois co Dé thu tap tan trong nude: CI, SOs. co Phai dé ngudi vi aspirin va a. salicylic tan 1 it trong nude & nhiét d6 cao va két tinh lai 6 nhigt 46 thip hon > kh6 nhgn xét dd duc or trong khi thir tap CI, SOs. Cich soi d6 dye? Cach so mau khi thir tap salicylic? Tai sao phai thém acid acetic trong thir tap salicyli Tra Wi: 0 Soi dé duc la nhin tir trén xudng trén nén den. o So mau li nhin ngang trén nén tring. © Via. acetic 14 1 sin phim trong qué trinh thay phan ciia aspirin, nén khi thém a. acetic vao ta s® han ché duge aspirin thity phan trong lite kigm nghigm. Cfn chinh xc, cn chinh xd khoan li gi? Khi dinh long, ta cn chinh xc hay chinh xée Khoan? Tai sao? Tai sao ko cfin v6i d@ sai lech lon: 50%? Tra loi: © Can chinh xée li cén t6i 0,1 mg, 0,01 mg hoe 0,001 mg tity theo 46 nhay cua loai cain phan tich sir dung, sao cho sai s6 cita phép cn khong qué 0,1%. © Can chinh xac khoan la cén dé dy 1 long khéng qua +10% lugng chi dinh. mer mLT* am trong giGi han can do thdi. o Can chinh xac khoan, vi sau dé ta 06 thé lap ti sé o Vitrong pp DL nay khodin sai s6 cho phép cl Tai sao phai trung tinh héa etanol? Giai doan trung tinh héa alcol, khi cho 1 giot phenolphtalein yao néu cé mau hong thi Lam sao, néu khéng mau thi lam sao? Tai sao phai dinh lwgng trong thau née 4? Tra ois © Etanol cé tinh acid > gay sai sé dinh long. co Néu cé mau hdng: ta thém HCI cho dd trong suét, ri thye hign trung tinh hoa = NaOH 0,1N dén khi thita 1 gigt NaOH 0,1N dd sé c6 miu hdng lot. Néu khéng mau: ta tién hanh trung tinh héa binh throng. é giit nhigt 46 khodn 8-10 °C. Trinh aspirin bj thity phan, ‘Trong pp DL nay, ta DL nhém chite nao cia aspirin? 1 Duong hrgng NaOH pu véi may duwong lwgng aspirin trong pp nay? Pp dinh lwong ( nghiém) nay khong t de (ko cho két qua ding) trong trung hgp nao? Tra lois © Nhém-COOH ol o Khiaspi bj thiy phan.9. sao chi kiém tap a. salicylic ma ko kiém tap a. acetic? Néu mu6n DL aspirin theo g6c ‘ster thi phai Lam sao? Tai sao ding cdn dé hda tan aspirin ma ko ding nude (khéi trang, tinh héa)? > Tri loi: © Via. acetic d8 tan, a. salicylic kh6 tan nén khi tap a. salicylic dat thi a, acetic ciing dat. 0 Tacho I hgng NaOH du chinh xée + dé cho pur xay ra hoan toan, 10i tién hinh DL thira trir= HCI, chi thi phenolphtalein, http://intranet,tdmu.edu, ua/data/kafedra/internal/pharma_2/metod_rozrobky/en/pharm/prov_pharm/ptn/ph armaceutical%20chemistry/3%20course/12%20Pharmaceutical%20analysis%200f%20esters%20and%20 amides%20of%20aromatic%20carboxylic%20acids%20and%20derivatives%4200f%20p- aminophenol.htmBai 5: TONG HOP METHYL SALICYLAT Co ché pur ester hoa. Phuong phap: chist tach. ‘San pham co ~OH phenol nén dé bj oxh > ¢6 mau, thity phan boi nhigt d6 Sau pu, dd trong binh bj duc do methanol bay hoi, née sinh ra khéng déng tan voi Methy! salicylat nén dd bi duc. Cau héi 1. Vai tro ciia methanol? Pu xdy ra theo chiéu thud Ii do? Tai sao phai dai vi acid salieylic khong? Tai sao? ~ Tae nhan thm gia pu va dung mdi héa tan, - Pw xay ra theo chiéu thuan la do: © Lam khan nuée, dun hoi lu, day dng silicagel. © HySOy dd kim xite tée va hiit nude. © Methanol du. = Viday la pu thuan nghich, néu khéng day kin thi nude bén ngoai vao cé thé lam pu di chuyén theo chiéu nghich. = Khéng nén cho thira H;S0s va acid salicylic vi H” gin vao OH cia methanol khé tach > giim higu suat pu. ~ Khéng cho thira acid salicylic vi né la chat rén, khé pur hodn toan, Khi thira cing kh6 thu hoi. 2. Néu dun hoi lu sai thi dd s€ ntn? Tai sao? Tai sao silicagel ding trong éng day c6 miu? - dd sé bi dyc do metanol bay hét, khéng con dung méi héa tan ché pham, nén dd ~ Silicagel c6 mau khée nhau khi khan nuéc va di ngim day nude dé nbjin biét han sir dung. 3. Tai sao phai khtr methanol? Sau khi thu héi hét methanol néu tigp tuc dun thi nhiét ké cé ting lén hay ko? Tai sao phai Jam ngudi qua Ié 6 bude 4° = visp hon héa trong methanol -> khéng thé thu de san pham tinh khiét. Ngoa chat dc -> anh hudng dén an toan khi sir dung sp. Khéng, vi dun cach thy trong n6i, nhiét 46 trong qua Ié sé thdp hon nhiét 46 si ciia née Li 100 Gt d6 sOi cita methyl salicylat la 220°C) i thy phan khi gap nude & nhiét dO cao. (lie nhe, dé yén 1°, kin? Cé nén cho thira H2SOs ra, methanol edn la é léu qua ester sé bj thily OH durac ko? Tai sao? Ruta lai 4, Diing NaHCO; bio hia dé kim gi? Tai sao? Cé thé thay NaHCO: ester v6i 10 ml nude cat dé Lim gi? = Dé loai acid salicylic ty do, néu loai kh6ng sch thi sp s& khdng trong. = Ding néng d@ bio hoa dé gidm lugng nuée, vi nhiéu nude thi methy! salicylat d& bj nhl ~ Khdng, vi ding xi dé thay phan ester. = Dé loai mudi natri salicylat, natri sulfat, NaHCO} 5. Giai don kim khan, c6 nén cho du NaSO, khong? Néu cho nhiéu Nay trong thi kim sao? Tai sao phai dun ech thiy? = Khéng, vi du NaSO, kim hao hut sin phim. = San phm kh6ng trong 14 do c6 lin acid salicylic, lic niy phai rita lai = NaHCO, va nurée cét. - Vikhi chiét tach = binh ling gan, sp co thé bi nhii, khi ting nhiét d6 cdc phan tir trong dd di chuyén nhanh hon, dé tach Iép, pha nhdi hon, lic dé Na;SOy dé dang hit nude, tich nude ra Khoi sp, dd tir due tré nén trong. 5. Pp dé tinh ché methyl salicylat khdc? = Chung eat phan doan: dudi ép suét gidm, khan nurée, 6, Dun héi lu ntn 1a ding? Vai tro cia Sng silicagel? Lic nao thi silicagel trong éng khéng con ding duge nita? 0, ma san phdm vin khong uu ding la: hé thong phai kin, va hoi nuéc trong ng sinh han khéng cao qua “4 ong, nue ludn day ong va di chuyén nguge chiéu voi dong khi bén trong. ~ Trinh dé nude bén ngosi vio trong binh pu khi dun hoi ru??? Khi n6 ddi mau tir xanh sang hong hoje vang (do CoC! khan hay ngim nude). C6 thé tai sir dung = cdich hoat héa lai trong tii sdy cho dén khi chuyén sang mau xanh,7. Néu khéng biét théi gian dun 1a 90°, thi lim sao biét dun dén khi ndo dimg? Sau pu acid salicylic eon hay ko? Lam sao biét? Sau pu trong dd co nhiing. chat nio? = Dun dén khi pu xy ra hoan toan, kiém tra = SKLM: chim cae vét: dd pu, acid salicylic. Lap lai SKLM cho dén khi khéng cén vet cia acid salicylic trong dd pur, nghia li pu da xay ra hoan toan, - Con, vi day 1a pu thudn nghich, higu suat khong thé dat t6i 100%, - Acid salicylic, methanol, H2SO,, née, methyl salicylat. 8. Vai tro cia acid H2SO, dd trong tong hop aspirin va methyl salicylat? Cu trite methyl salicylat ¢6 ging aspirin ko? = Aspirin: xtc tac. ~ Methyl salicylat: xite tie + hitt made. = Gidng, cé phan ester. 9. Giai thich hign tuong nhiét gidm tir 64 °C cdn 60 °C khi chung ct methanol? ~ Vimhigt d6 s6i ctia methanol 1d 64 °C, nén khi bay hoi, tiép xtc lam nhigt ké chi 64°C, sau d6 nhigt dQ giim din do lrgng methanol cang lite cdng it 10. Cé thé thay Na>SO, khan = = Voi sng: CaO, MgSO, CaSO4, K2S0, 14. Co ché pu téng hop methyl salicylat? - ad 412. Dé nghi pp dinh tinh va dinh hrong methyl salicylat? Dinh tinh: © dya vio -OH phenol, cho tac dung véi FeCI3 -> phtte mau tim. © Do ti trong hay khdi hrgng riéng ciia methyl! salicylat: 1,1825 g/ ml. © Do diém dong dic (hay diém chay): -8,3 °C. - Dinh Iugng: o UV-VIS, HPLC. © Dinh lugng géc ester = NaOH 0,1 N dur, chudin dG NaOH 0,1 N du'= HCI 0,1 N, chi thi do, phenol. 13.Bai 6: Kiém dinh methyl salicylat Cau hoi 14, Nguyén tic dinh lwgng methy! salicylat? Nguyén tie nay thong 4p dung cho nhimg chat c6 edu trie ntn? Ap dyng cho chat c6 céu tric amid de ko? Tai sao? "Dinh Iugng thira trit, Céu trac ester. Khdng ap dung cho chat e6 céu trie amid duge vin6 bén hon, kh6 thity phn hodn toan -> dinh lang ko chinh xe, 15, San pham thiy phan cia ester methyl salicylat? * Acid salicylic va methanol 16. Tai sao so mau voi dd V7 (co mau vang)? Cho biét 1 thude gidm dau cing dé bj bién mau vang (cé amin thom b4c 1)? * Vi trong cdu tric e6 -OH phenol dé bj bién mau vang trong qué trinh bao quan. = Paracetamol. 17. Dinh nghia cin chinh xc, va chink xic khodn? Trong bO mon, “ein chinh xc” thi sai sé n6 Ki bao nhigu:1 g, 1/10 g, 1/100g, 1 mg, 0,1 mg. Tai sao trong dinh rong cé y chinh xe khoan? "Sach thye hanh trang 19 & 25. = 0,1 mg . TT : = Visau cn ta lip ti s6 86 k= aT > triét tiéu sai s6 do cn. (nhung chi trong gidi ‘han cho phép cua pp dinh lugng. VD: ko thé can dur 100g rai lap ti sé nhu trén) 18. Tai sao diing cdn lam mdi truvg trong djnh lgng? Khi cho chi thj dé phenol vio dd dinh long cé mau gi? Tai sao? = Vi methyl salicylat tan tot trong con. = Mau vang, vi methyl salicylat 06 tinh acid nhe do g6c -OH phenol. 419. Néu khi cho chi thj dé phenol yao ma dd cé mau vang thi gd trung tinh phai lam sao? ‘Tiép sau gd trung tinh héa, cho SOml NaOH 0,1N vio -> dd ¢6 miu 46 -> Chuan do dén khi nio? = Trung tinh hoa = NaOH 0,1N cho dén khi dur 1 gigt NaOH Lim dd c6 mau d6 thi dimg. Dén khi 1 gigt thira HCI0,1N vao lam dd cé mau vang. i sir long HCI sir dung li V ml, thi lrong NaOH tac dung trén géc ester Ja bao nhiéu? Cho biét 1 duong lugng NaOH tac dung may duong lugng methyl salicylat? = 50-V (mb). = 1 duong long methyl salicylat. 21. 6 gd trung tinh héa, khi cho chi thj vao, néu dd cé mau vang thi phai lam sao? New mau xanh durong thi phai kim sao? = Néu dung dich e6 mau vang thi tite 1 m6i trudmg dang acid, ta trung tinh hoa = ‘NaOH 0,1N dén khi thita 1 gigt NaOH lam dd déi mau xanb. = Néu dung dich c6 mau xanh, ta cho HCI vao cho dén khi dung dich déi mau vang, 10i tién hanh trung tinh hoa = NaOH 0,1N nhu trén. 22. Néu sy khée nhau ciia phn trung tinh héa trong giai dogn kiém giéi han acid va 20. dinh long? Ki han acid Dinh krgng = Trong dd chi cé cn = Cén + methyl salicylat = Chi thj xanh bromo cresol ~ Chi th dé phenol = Mau chi thj ving — xanh dong ~ miu vang - 46= pH chi thj3,6~5,2 ~ pH chi thi 6,8 ~8,2 inh tinh A mudn thir phan nao cia methyl salicylat? Tiia tinh thé tao thanh [a gi? = Tra loi: Thir géc ester cia methyl salicylat, Tua tinh thé tao thanh la acid salicylic. 24. Trong phan thir tinh khiét, néu cach so mau dung dich? C6 con cach so miu nao khac ko? = Tra loi: Trong bai nay sir dung pp so miu la nhin ngang trén nén tréng (do éng nghiém dang sir dung la logi day tron). Trong DDVN cé qui dinh cdn ¢6 pp so mau nhin trén xuéng trén nén tring voi dng nghiém cé day bing. 25, Mau va pH ciia chi thj Bromocresol? = Tra loi: Vang ~ xanh durong. pH 3,6-5,2 26. Tinh ti trong dd méu thir cia minh? (Xem cach tinh trong DDVN) 27. Tai sao gd nay trung tinh héa con truée rdi méi cho ché phim vao (khdc vi phan dinh lwgng)? Tra loi: Vi cdn cé thé lin acid, nén ta céin loai bé sai s6 do cOn trude khi tién hanh thir gigi han acid ciia methyl salieylat -> kira xem c6 Fin tap acid ko? = Trong phan dinh lwong, ta tién hanh trung héa luén ca con va methyl salicylat nham loai hét cdc sai sé cé thé xay ra (do cn, hay do tap acid), truée khi tién hinh dinh lugng = NaOH 0,1N 28. Tap acid cé thé 6? "Tra loi: Acid salicylic vi HO. 29. Pp dun hdi lu dang ding cé ding hay ko? Vi sao = Tra ldi: Dung, vi ethanol bay lén chua t6i 2 dng sinh han da roi xuéng 30. Cé céch nado khac dé djnh lrgng methyl t ko? = Tra loi: HPLC, UV. 23.Bai 7: TONG HOP SALICYLAMID Cau h Amoniac hoa long trong diéu kign nao? Sinh han dé lam gi? Nude trong binh pv tir dau ma c6? DD ampniae dim dic bao nhiéu %? Ap suit cao Ngung tu nuée bay hoi dé kéo theo NH,OH, do NH,OH tan tét trong nude. Nurée tir dd amoniac dim de - 25-28% ng nig - Ko, vic bai aspirin la dé tranh san pham aspirin bj thiy phan, bai nay git nhiét d6 6 60-70 °C dé: Xem cau tiép theo Nhigt 6 qué cao (+100 °C) trong khi amid héa c6 anh huéng dén higu suat tong hop? - NH,OH bay hoi nhiéu cé thé gay giam higu suat tng hop - Methyl salicylat co thé bj thiry phan - Sin phim salicylamid e6 thé bj oxy héa, Nhin cdch thye hién pu, tai sao biét khi thue hién pu chic chin NH;OH bay hoi ma ko ngin de? = Thye hign trong ti hut. ‘Tai sao san pham dé bi oxy héa? Tai sao ban dau binh pu bi duc, sau do thi trong lai? = Do c6 nhom—OH phenol Do ban dau trong dd c6 nuée, NH,OH la dung méi phan ewe, va Methyl salicylat li dung m6i khong phin cye nén 2 turémg nay khong tan vao nhau, khi c6 tac dng khudy s& tgo nha tuong > due dung dich, Sau do khi pu két thi, trong dung dich c6 NH,OH du, nude, CHOH va salicyladmid tan trong nuéc néng nén dung dich trong sué - Tuy nhién cdc pu tong hop nay khéng co higu suat 100%, do methyl salicylat bi thay phan | phan thinh acid salicylic phan img voi NH,OH tao thank mudi amoni salicylat tan trong nude nén dung dich van trong suét. = Sau khi bj thay pl n cho amoni salicylat khong cOn kha ning pu amid héa dé tao salicylamid nita vi Khéng cén tac nhan acyl héa Nito ciia amoniac Co ché phan img? Téc nhan acyl héa bai nay? Tac nhin acyl héa manh nit li 2 ~ Céng di nhan - Ester methyl salicylat. - Tée nhan acyl hoa manh nhat: acyl halogenie > anhydrid acid > ester > acid. - Methyl salicylat co nhom methyl day dién ti yéu hon nén Carbocanion duong nhiéu hon Ethyl salicylat > kha ning pur amid héa cao hon, - Acid salicylic trong dung dich phan ly cho ion H” & -COO’, pu tgo mudi amoni -> ko cho pu amid hoa, > Kha nang pur amid héa yéu din theo thir tyr Methyl salicylat > Ethyl sali Tai sao khi tinh ché aspirin phai git nhigt 46 60 °C, cn véi salicylamid ¢6 thé ding nude ~ Aspirin c6 lign két ester dé bj thiiy phan é nhigt d6 cao nén phai gitt 6 60 °C, edn salicylamid 66 lién két amid bén vi nhigt hon nén ¢6 thé ding nude séi. ich cia giai doan dun bay hoi hn hop sau pu? Dé loai NH,OH, CH3OH, | pI 20 gitip san pham dé két tinh hon, - Nhung muc dich chinh la dé loai NH,OH giip sin phim dé két tinh hon,10. Tai sao khi dun bay hoi hén hop khéng durge dun qui can? - I phan san phim sé bj oxy héa. - Trdnh két tinh tap chung véi sin phim. VD: amoni, CI, SO,” 11, Hay 48 nghi_1 cach khéc dé loai NH,OH, giip sin phim d ~ Trung hoa NH,OH. VD: ding acid HCI, nhumg sau dé phai loai tap NH,Cl 12. Salicylamid nam trong nhom thudc gi? ~ NSAID. 13. Trong kiém nghiém salicylamid, ngoai Cl, SO,” ngudi ta con kiém tap cation nio? NH," 6 dang mudi. 14, Gitta acid salicylic va benzoic, acid néo manh hon? ~ Acid salicylic vi nhém —OH va ~COOH dé tgo ester ndi phin tir Kim cho H” d8 bj phan ly hon. Nén ngudi ta gidm tinh acid ciia né = cdch chuyén dang ester (aspirin), amid (salicylamid). 15. Phuong phip tinh khiét sit dung trong bai nay Li gi? Tai sao s4y 6 70 °C? Tai sao tinh thé to thi t6t hon? - Ket tinh lai Vi sin phim dé bj oxy hoa & nhiét d6 cao do cé nhém —OH phenol. - Vitinh thé to it chira tap hon. 16. Cé thé tong hop salicylamid bing phuong phap nao khac khdng ding céc este salicylic? C6 2 phuong phép khic: 1. Anhydrie salicylic © 2. Acyl salyeilat véi tae nhin COCI Laws: Khi thye hign pu amid héa phai lau sach silicon edt con thira trén sinh han va 6 erlen, sau d6 bdi silicon méi Khi dun dé c6 dung dich phai khuay lién tue, cho dén khi thé tich < 50 ml. Giai doan 3 (tinh khiét sin pham):xép gidy loc phai cao, phai lun luén c6 sin nude sdi, trang gidy loc = nude s6i trude, khi loc ludn dé day gidy loc + dat bercher trén bép (giit nhiét) -> tiép tue cho én khi loc hét bercher, sau cing néu sp két tinh trén gidy nhiéu thi ding nue s6i riza 1 lan, Nhanh chong dem ca phéu Igc va bercher lén bép (ké ca chua loc xong hét, gd nay phai cam phéu Igc = tay), Sau khi sp trong bercher tan hét thi nhin duéi phéu loc + kéo sp bam trén thanh bercher xuéng. Nhe nhang dit bercher 6 noi yén tinh dé ngudi ty nhién, sau cing méi lim lanh = nude di. Nhu vay sp sé thu de nhiéu va dai, dep.BAI 8: KIEM DINH VITAMIN B, VA Be Tém tit & so sanh: Thiamin hydroclori Dinh tinh: 1.1. Séch TT: kali ferricyanid, CI (AgNO3). 1.2. DBVN IV: IR, Cl (AgNOS), kali ferricyanid (2 tests du thude nhém wu tin) 1.3. BP 2013: IR, Cl (AgNO3), kali ferricyanid (2 tests du thuge nhom wu tién) 1.4. USP 2012: IR, CI (AgNO3). Kiém nghiém: (thir tinh khiét) 2.1. Sach TT: khong 6. 2.2. DDVN IV: a, BO trong vi mau b. pH: 2,7-3,3., c. HPLC: tap chat lign quan. 4. Sulfat: < 0,03 %. ¢. Kim logi ning < 20 ppm f, Nude: < 5,0 % cho 0,40 g ché pham. g. Tro sulfat trong 1g ché phim: < 0,1 %. 2.3. BP 2013: ging DVN IV. 2.4. USP 2012: a. Tro sulfat trong 1g ché phim: b. Gigi han nitrat: c. HPCL: Tap lign quan < 1,0.% d. pH: 2,7-3,4 Ge: < 5,0 % cho 0,40 g ché phim is: mau thir va mau tring ko Iéch nhau qua 0,025 ic dd: trong suét, vi khong duge dim hon dd V7 hay VL7 <0,2%. fch TT: khdng 6, 3.2. DDVN IV: dinh lurgng méi trudng khan trong 2 phat. DTD xée dinh = do dign thé, Lam thém miu trang. 3.3. BP 2013: giéng DBVN IV. 3.4. USP 2012: HPLC. Vit. B6: Pyridoxin Hydrocl Dinh tinh: Sach TT: pur véi sit (I11) clorid, Cr (AgNOs) 1.2, DDVN IV: IR, Cl (AgNO3), UV, TLC (2 tests du thuge nhém 1) 1.3. BP 2013: IR, Cl (AgNO3), UV, TLC (2 tests dau thude nhém 1) 1.4, USP 2012: pur véi sat (III) clot ._Kiém nghiém (thir tinh khiét): hoa tan 2,5 g ché pham trong 50 ml nude cat. 2.4. Séch TT: a, Kim logi ning < 20 ppm b. pH: 2,4—3,0. 2.2. DBVN IV: a. Dé trong va mau sic: trong sudt, va khong duge dam hon dd V7 b. pH: 2,4— 3,0. c. Kim loai nging < 20 ppm 4. TLC e. Mat khéi lurgng khi say 1g 6 105 °C: < 0,5 % f. Tro sulfat 1g ché phim: < 0,1 %. 2.3. BP 2013 A : a. DO trong vi mau sc: trong suét, va khéng duge dam hon dd Y7 b. pH: 2,4— 3.0.©. HPLC 4d. Kim logi ning < 20 ppm e. Mat khdi long khi say 1g 6 105 °C: < 0,5 % £. Tro sulfat trong 1g che pham: < 0,1 % 2.4. USP 2012: HPLC, UV. 3. Dinh lugng: 3.1. Sach TT: pp acid — base méi trudmg khan, Chi thi tim tinh thé, 3.2. DVN LV: pp acid — base moi trudmg khan. Chi thj tim tinh thé, 3.3. BP 2013: pp acid — base méi truémg khan. DTD xic dinh = do dign thé, Lam thém mau tring. 3.4. USP 2012: Separately add 25.0 mL of isopropyl alcohol to 5 mL cach of the Standard solution and the Sample solution. Transfer 5 mL of each of the resulting solutions to separate, glass- stoppered, 25-mL graduated cylinders or test tubes, and add in succession, mixing after each addition, 1.0 mL of Buffer, 1.0 mL of a 0.2-g/mL solution of sodium acetate, and 1.0 mL of water. Cool to 25°, add 1.0 mL of Color reagent, and shake vigorously for 10 s, accurately timed. Determine the absorbance 90 s after the addition of the Color reagent. Repeat the procedure both for the Standard solution and the Sample solution, but substitute 1.0 ml of a 50-mg/mL. solution of boric acid solution for the 1.0 mL of water. Cau h Thiamin hydroclorid (Vitamin B1) - Thue vat: trong men, im lia mi, cdm ggo, du twong, du phong ‘D6ng vat: trong gan, than, thit heo, long do trimg, sita. 1, Tén thudng goi cla Thiamin hydroclorid? Pu dinh tinh 1 dé dinh tinh phan nio cia Thiamit yydroclorid? Chat nao sé phat quang trong pur dinh tinh nay? Tai sao phat quang duce? Vai tro cua dung dich butanol? Tai sao acid h6a thi huynh quang mat di? C6 thé ding pu nay dé dinh Iugng de khong? - Vit. BI ‘Thiamin. OH -en -ol cua p: Thiocrome: do n6 da dong vong -> céu trite cimg chiic hon, dé phat quang hon, lic tan trong butanol, Bude song soi UV 1a 365 Thiocrome it tan trong nude, dé tan trong butanol, nén ta ding dd butanol dé hoa tan ‘Thiocrome, sau d6 soi UV 365. Do Thiocrome khdng bén trong mdi trrdng acid manh, bj mé Vong, nén khong edn phat hujnh quang due nia, Neu kiem héa sé déng vong tro li. ‘Duye, do phat huynh quang = huynh quang ké. : dinh tinh 2 dé dinh tinh phan nao cia Thiamin hydroclorid? Cé céch nao khic dé phan biét Thiamin vi Thiamin hydroclorid khong? HCI = C6 2cécl © Dung giiy qui do pH. Thiamin cé tinh base (cé nhiéu Nito trong phan tix), Thiamin hydroclorid cé tinh acid. © Thiamin khé tan, Thiamin hydroclorid d& tan trong nude. Dé nghi phuong phap dinh long thiamin hydroclorid?- Ppacid — base: chun 46 HCI = Dd dinh Iugng NaOH 0,1N, chi thi phenolphtalein (I ml of 0,1 M solution of sodium hydroxide corresponds to 0,03373 g of thiamine hydrochloride.) - Pp Fajans, dd dinh lwong AgNO3, chi thi xanh bromophenol (1 ml of 0,1 M silver nitrate solution corresponds to 0,01686 g of thiamine hydrochloride.) © Nhuge diém 2 pp trén li khi Thiamin bi ¢gidm him long nhung két qua dinh Iuong khéng thé hién duge diéu 46, do tién hanh trén phan HCl. - HPLC. dinh: - Dw phéng va dieu tri thiéu Vitamin B1. - Viém da than kinh,Pyridoxin (Vitamin B6) 1, Phin ing dinh tinh 1 6 thir phan nio cia Vitamin BO? = -OH phenol : 2. Phan ding dinh tinh 2 dé thir phin nio cia Vitamin B6 2 - HCl 3. Cho biét 1 purhéa hoc khae dé dinh tinh B6 2 co cl Luru ¥ gi khi thir tinh khiet ? Thir tinh khiét cia pyridoxin hydroclorid e6 ding nude dun s6i dé ngudi ko? Tai sao? ~ Diing mrdc dun séi dé ngudi = C6. Vi: thir pH, va kim loai ning? 5. Tai sao phai thir giéi han kim loai ning ? Tai sao thir gidi han kim loai nang lai qui ra chi ? thioacetamid 14 gi? Vai tro ? Kim loai nang la gi ? VD ? Thir kim loai nang soi ntn ? Mau soi la mu ciia chit gi ? Tai sao cho 2 ml dung dich B vio éng chun ? ~ Kim logi ning dc véi co thé, de bigt 1a khi tich Idy trong thd gian dai, - Vichi la kim logi phé bién, va dd chuan sir dung 1a chi. nos = CHsCSNH2: yt % is hen / d - Vai tré : dé tao H2S pu véi kim loai nang thanh két tua dang cn den. - KL ning 1a kim loai c6 khdi long rigng Sg/em’. VD : Pb, As, Hg, Cd, Au, Bi...~ Mau la mau den ciia mudi kim loai nang va ru hujnh. VD : PbS, HgS. - Theo ly thuyét ta sé soi miu dung dich: nhin ngang trén nén trang. = Tuy nhién, mudi sulfit kim loai nang khéng bén @ pH 3,5 nén phan hay thinh hu huynh mau tring kim duc dung dich. Vi vay trong bai nay ta phai soi tir trén xudng trén nén tring. Glycerin dé hé try quan sat. - 2ml dd thir : Bong vai tro nhu a chat di chiéu ciia kim loai nding khae kh6ng phai la chi, 6. Trong bai nay pw dinh Iuong la dé dinh long phan nao ciia Pyridoxin hydroclorid ? Tai sao dinh lugng trong mdi trudng khan 2 Acid formic dé lim gi? Anhydrid acetic dé lam gi ? Ngoai cach sit dung do dién thé va chi thi tim tinh thé, cdn cach nao dé phat hién DTD ko ? - Dinh Iuong phan Pyridoxin, - - Vi Pyridoxin la m@t base yéu trong méi trang nude, nén khéng thé dinh lrgng true tiép trong moi truémg nude duige. - Acid formic dé héa tan che phim va tao mdi truéng khan. - Anhydrid acetic dé gitt ede anion khéc (CI) khdng pu gay sai sé thiéu. - Céch khdc dé phat hién DTD: 7. Trong dinh long, cn 0,15¢ li cén chinh xc hay chinh xc khodn ? Gidi han cin 0,15g ché phim a bao nhiéu ? dinh nghia cn chinh xéc va cn chinh xéc khoan ? Sai s6 ciia edn phan tich tro PTN [a bao nhiéu ? Mau trang 1a gi ? - Cn chinh xée khoan. - Tir0,135¢-0,165g. - Dinh nghia : SGK/ 19 & 25. - 0,1 mg. = Mau trang la mau giéng nhu mau thir nhung khong c6 ché pham. 8. Luu y khi sit dung chi thi tim tinh thé - LAy diing thé tich. - Dung cy ly phai kh, néu khong s& sai mau. - Néu lin nudc sé gay sai s6 dinh lugng. 9. Phuong phap khée dé dinh lrong Vitamin B6 = Ppacid ~ base : chun d HCI = dd NaOH 0,1 N, chi thi xanh bromothymol 10. Chi din u tr thiéu Vitamin nhém B: ngudi nghién regu, suy thin phai tham phan.BAI 9: DINH TINH CAC CYCLIN KIEM DINH CLORAMPHENICOL Removal of dimethylamine reduces activity. Addition of higher CH, | alkyylamines reduces activity. N—CH, Stereochemical configuration @ iis important for the activity ,-OH— Substitution of the amide by |_| aldehydes or nitrites reduces the k activity. The coordination of the metals platinum and palladium on Mr ring A of tetracycline and doxycycline increases activity. ‘The system Keto-ethanol Ring D is important for activity. Stereochemical configuration at C-12A is important for the activity. Modifications at positions 1, 3, 4A and 10 result in loss of activity A. DINH TINH CAC CYCLIN: 1. C6 do nang suit quay cue kiém tra tinh khiét tetracylin duoc khong? Dua vio dau ? - 0 - _cacbon bat déi va dong phan quang hoc. 2. Trong tetraeylin bao quan khong kithi tap chit gi dé xy ra? Ko 6 tic dung va dée nia va hai thn ni - dang epitetracylin ..22? 3. Tai sao nhém cyclin c6 miu ving ? 1. Phan Gng dinh tinh chung : 1, Phan Ging mau v6i FeCl, 4, P.u F3CLa do nhom nao? - nhom OH PHENOL tao phite mau chelat. 1.2, Phan ing khir v6i thudc thir Fehling: 5. Phan img véi thuée thir Fehling li do nhom gi? - -CHO 6. Thanh phan cia thudc thir Fehling? - Fehling A: dd CuSO4 - Fehling B: hén dich cia NaOH véi mudi tartrate ca Na va K c6 c6ng thite: NaQOC-CH(OH)-CH(OH)-COOK 1.3, Phan ng phat huynh quang: Il Phan tng dinh tinh phan biét : 11.1, Phain ving voi H2SO4 aa 7. Thue chat cua phan ung cua H2SOx la gi? - laphan ung tach loai nuoc tach o vi tri R3 ll, Phan tng xdc dinh mudi hydroclorid: 8. trong phan dinh tinh trong da so truong hop khi cho AgNO3 vao se cho Tua trang nhung co truong hop lai cho Tua den?- Vikhi dung HINO3 acid hoa da acid hoa k htoan nen AgNO3 tdung voi NaOH Tao AgOH. khéng bén tao Ag:0 co mau den, IV. Binh danh khang sinh thuéc nhém Cyclin: B. KIEM DINH CHLORAMPHENICOL: |. Binh tinh: rs —€ —eney on pT ae a ap Pn St a NaCl + AgNO3 > AgCl| + NaNO3; AgCl| + 2NHjOH —; [Ag(NH3)3]Cl + 2H 0. I. Dinh lwong: 9. Phan dinh luong phan do quang vi Sao k dung giay co Mui thom Lau coc thach anh 2 ~ nhung khan giay co Mui da so trong cthue etao se co vong nen se hap Thu Tia UV nen se gay sai so khi do quang 10. Sit dung céc do nao trong dinh rong? tai sao? ~ Céc thgch anh vi do quang bude sng 278 nm trong viing tit ngoai 11, Ui & Nhuge diém cia pp dinh lung ? - Uudiém ; dé lam, tuong doi chinh xac. - Nhuge diém © Khéng phan bigt duge suat quay cute). © Phai cé trang thiét bi do quang. © Ngudi tién hanh phai qua dao tgo chuyén mén. 12. Lum ¥ Khi tién hinh dinh hong : - Hoa tan phai hoan ton, - Dé ngudi rdi méi thém nude néu kh6ng sé sai thé tich. 1g phan c6 hoat tinh cla Chloramphenicol (phan biét ~ do nang Do quang 6 278 nm > vung tir ngoai > ding céc thach anh. ‘TEST ON PURITY Acidity. To 1 gof the drug is added 2 ml of 96% alcolio! R neutralized by phenolphthalein, carefully mixed for 1 muinute and filtered. Filtrate after the adding of 2 dops of phenolphthaiein solution R and 0.08 ral of 0.1 Msolution of sodton hydroxide should paints in the pink color that persists for 3 minutes. ASSAY. Nitrtometry (ater the previous recovery of aromatic nitro-group) Approximately 0.2 g of the product (exact weight) placed in a conical flask with capacity of 100 ml, ad 10 ml of Indhochioric acid R and carefully in small portions 2 of zinc powder R. Thea add another S ual of Indrochloric acid R wask the Walls of the Dask. and after complete dissolution of zine power P (cau be heated) solution quantitatively transfer ito a glass for dinzotation that is cooled with ie, add 1.5 g of potassium bromide R aad slowly tate by 0.1 Af solution of sodlum nitrite, Titatioa considered complete when a drop of liguid was taken out aRer 3 minutes after adding of 0,1 A soltion of sodium nitrite will cause a immediate blue color ofthe starch-iodine piece of paper. ae lee aetna OLE} we we fee {02 + 2KI-+ SHCL + Ty + 2NO} + 2NaCl + 2KCI+ 2420. Eq = Mem. 1 ml of 01 Msolutian of socom nitrite coresponds to 0,03231 g of lacvomycetin,Copper-iodometry, tration by substitute Approximately 0,1 g of product (exact weight) dissolved in 10 ml of water R. ad $ ml of 1096 sodian hydroxide solaion and 3% copper sulfate. hake the mix ‘uring 2 minute, filtered through a small cotton ball (not very tight, which can eater on 1-1,S cm in the tube of the fnnel) and washed 3 times with water, $m in each portion To the filtrate add by érops acid sulfate dilted solution R to the discoloration, 2 g of potassium iodide R and titrate by 0,01 M solution of sodium thiosulfate tothe bleaching (indicator - sarch soletion Rl. poe = “et oe pet cnc, eo ser {pte wn hn 2CuS04 = AKI -+ 1p + Curly, +2K2S045 Ig + NayS;O3_» 2Nal + NaySOg- {In parallel conzol experiment is conducted. 1 ml 9,01 Mfzodnun thiomlfat soltion conesponds 0,00646 g of laevousycetn, http://intranet,tdmu,edu, ua/data/kafedra/internal/pharma_2/metod_rozrobky/en/pharm/prov_pharm/ptn/ph I%20chemistry/4% ise/24%20Quality% lysis%200f%20the% icines%2 m%20antibiotic?%E2%80%99s%20group%200f%20the%20alicyclic%20and%20aromatic%20rows.htmDINH TINH PENICILLIN KIEM DINH STREPTOMYCIN SULFAT G,V : nhom penicillin c6 dién, khong bén trong méi trudng acid hay base. Phé khang Khudn chit yéu ld gram (+), yéu trén gram (-) khong tac dong trén true khuan gram (-) b. Amoxicillin: penicillin nhom III A (Ampicillin, amoxicillin...), yéu hon penicillin G trén gram (+), nhung manh hon trén gram (-), bén véi acid, nhung nhay cam véi beta-lactamase, hap thu kém qua Penicillin G Penicillin V HO \ Amoxicillin > Corché tic dong dua trén vige tre ché VK ting hop thanh té bao do tao hop chat bén véi enzyme tng hgp thanh té bao VK, lim bat hoat enzyme ny. Phd KK cia mt penicillin phu thude vo: ~ Cu tric - Kha ning xuyén ming VK gram am -Tinh nhay edm véi betalactamse - Ai lye v6i enzym muc tiéu transpeptidase - Téc d6 bi bom ra ngéai & VK gram am. B-lactam mechanism of action ABX-free Cell Wall Synthesis ern ren ceph Mono cota —_8l0ck of transpeptidase activity interrupts cross-linking & cel! wall synthesis Vii D-Ala-0-Ala structural mimics> Vikhudin dé khang beta-lactamin theo cfc co ché sau: © Dé khang enzyme: VK san xuat f -lactamase. Y Khac phuc: két hop thém | trong cac chat sau: HCOOH Q. 4 N- ‘CHZOH Hq acid clavulanic Sulbactam o Dé khang khéng enzyme = Thay doi tinh tham thau cia mang té bao. * Bién mat hoic bién doi cdc PBP. ‘* Hinh thanh hé thong bom bén trong, day thudc ra khdi té bo. ¥ Néu ding két hgp a. Clavulanic hay Sulbactam thi cing khong higu qua. IL. Thye hanh: IL1 Dinh tinh ede peni LL Phin dng djnh tinh chung : Co ché hydroxy amin li 1 te nn ai nn (do 66 N gid dign tit) sé tn cong vo Carbocation cia vong betalatam, kim mé vong, sau 46 dong pu tao hgp chat c6 mau xanh, 1.1.2. Phiin tng phan bigt ; a. Phan tmg mau voi H)SO.d¢: ~ Corché: do vong f lactamase khong bén trong mi trudng acid nén bi mo ving, sin phim e6 miu??? b. Phan img véi Formaldehyd trong H2SO, OH H. QO ‘ a ama oD phenol formaldehyde oO ‘OH aakeie §¢. Phan img vii thudc thir Fehling: 11.2 Kiém djnh streptomycin sulf ~ Khang sinh nhém aminosid, dye chigt xuét tir ndm Streptomyces 12.1 Dinh tinh: a. Phan tng do nhém guanidin: tao NHs bay lén lam xanh gidy qui NH HoN@ ~NH2 Guanidin b. Phén tng do nhom streptose: rn Te | Streptose Mattol phhite Fe mau tim Cau héi: 1. Nhuge diém cia pp dinh luong may 132 = Khdng xdc dinh duge chinh xc hoat lyre khang sinh do khong biét khang sinh c6 cin nguyén ven khi dink lrgng hay khong. 2. Tai sao phai lay wi tri mat d ang can do trong khoan 0,24 do quang & 535 nm ‘Néu cho thita qué nhiéu (acid H;SO, khéng thé trung hda hét) thi sé tao tia Fe(OH); e6 mau néu d6_ lm can tr do quang gay sai sé dinh lugng. = viphén st amoni cé miu ving nhat nhat nén durge chon i ko? (Tai sao phaiBAI 11: BINH TINH PHTALAZOL KIEM DINH SULFANILAMID PHTALAZOL (Phthalylsulfathiazole) I. Ly thy - ’Phthalylsulfathiazole thuéc nhém thudc goi la sulfonamid. Thudc la mot khang sinh phé rong, c6 thé diéu tr cdc loai khac nhau cla nhiém tring bao gdm ca rudt. Co ché tac dng phy thudc dya trén sy d6i khang canh tranh voi acid para-aminobenzoic va Wc ché hoat déng cia synthetase dihydropteroate, ma lan lugt dan dén téng hop suy giam acid dihydrofolic va két qua la chat chuyén héa 06 hoat tinh cia né la can thiét cho sy téng hop purine va pyrimidine. - Thudc duge chi dinh trong digu tri bénh kiét ly, viém dai trang, viém da day rudt va phdu thuat rust Cac tac dung phy cé thé bao gém cac phan tng di trng, suy vitamin B, mat bach cau hat, thiéu mau bat san. ~ Phan tng téng hop: Qo N\ fo) Ss Sy Xx» Ha ‘SO,NH J 9 N o H " N (sulfathiazo!) H ° ‘COpH Phthalic anhydrid Phihalylsulfathiazole (phtalazol) Il. BINH TINH: ting véi B- naphtol: Pu nay dé dinh tinh phan gi? viét pu? - Pu nay dé dinh tinh nhém Sulfathiazol sau khi bi thay phan, bing céch diazo héa nhém amin thom bac 1 alia sulfathiazol tao hop chat ob mau dé cam. ~ Phan tng xay ra theo 2 giai doan: Giai doan 1: thiy phan in o oe roo Hel “On BS coon - 2 6 ON : rye ‘Sulfathiazol acid phthalic anhydrid Giai doan 2: pu’ diazo héa nhém amin thom bac 1 NH, t= = oo aa HCL a aan Tey, Jee —o Bo2. Vai trd ciia HCl trong pu nay? Thay HCl = NaOH dé thy phan de ko? - HCI dé thiy phan phtalazol, va tao méi tréng cho pu diazo héa. - Burge, nhung phai trung hda lai = HCI vi pur diazo chi xay ra trong méi trvéng acid HCI, nhigt 46 anh 3. Tai sao phai lam lanh éng nghiém? (didu kién thuc hién pw diazo héa - _Nhiét d6: lanh 2-5 °C, do mudi diazoni bén & nhiét 46 thap, va acid nitro dé bj phan hiy - Amin thom bac 4 - _ M@i truéng: Acid nitro (hay mudi nitrit/ acid) - HCI du vi tranh phan ting ghép di 06 thé xay ra gitka mudi diazo méi tao thanh véi amin tw do cdn chua phan Ging IL4 Phin ing v6i resorein: Hai: 1. Pu nay dé dinh tinh phan gi? Viét pu? - Purnay dé dinh tinh phan acid Phthalic anhydrid duge sinh ra tr pu thy phan cia Phtalazol. ENTIFICATION D. (BP, SPU, suppl. 2) Reaction of uoresceine formation (or rest of phthalic ci Toi gail 05 gf esorino! Ran 0.3 wl of sulphuric ac Rnd heat on a waterbath wail a homogenous mictuei cbrained, Allow to cool. Add Smal of dite scion inchoxide colton R Dil Ot of hs Brom ed mre 2° rl with noter Am intense greeauorexcence appears hich disappears oe aiiaton as i Phthalic anhydrid | ~ i AX AA resorcin Natri fluorescein (cho huynh quang xanh) - _ Natri thioresin (trong mdi truéng kim) cé cAu tric cizng chc, nhiéu néi déi nén cé thé phat huynh quang. KIEM SULFNILAMID I. LY THUYET: 1.1 Téng hop: 02 NHe NHCOCH, CO HNO, Fe, Ct CHycO0 Hy S0y NHCOCH, NHCOCH, NH;*C! NH, HOSOI Niy es Nacos HO ct Nee Hy NH,1.2. Corché tac dyng va phé khang khudn PABA (para amino benzoic acid) 4 ngudén nguyén liéu can thiét cho vi khuan téng hop acid folic dé phat trién. Do o9 cu tric héa hoe gan gidng voi PABA nén sulfamid da tranh chp voi PABA ngan can qua trinh téng hop acid folic cla vi khuan. Ngoai ra, sulfamid cdn irc ché dihydrofolat synthetase, mdt enzym tham gia téng hop acid folic. Vi vay sulfamid la chat kim khudn. Té bao déng vat 06 vii va vi khudn nao c6 thé sir dung tryc tiép acid folic tir ‘méi truéng thi déu kh6ng chiu anh huéng cia sulfamid Ve mat ly ‘huyet, phé khang khudn cia sulfamid rat rong, gom hau hét cac cau khuan, trye khuan gram. (#),va (-). Nhung hién nay, ty 8 khang thuéc va khang chéo gita cdc sulfamid dang rat cao nén da han ché viéc str dung sulfamid rat nhiéu. Vi khudn khang thudéc bang cach tang ting hyp PABA hoac giam tinh thm voi sulfamid. Il. BINH TINH: IL1 Pw azoic héa véi dd B- naphtol: = Pu dé dinh tinh nhém amin thom bac 1 cia Sulfanilamid 4H, | i= "oN NaNO, nN Hel ee Haan On nN, oye, AUC Hei 1. Vai trd oa HCI? Sulfanilamid 06 tan trong nue, base, acid ko? = Dé hda tan ché pham va tao acid nitro tham gia pu' diazo héa. - Sulfanilamid khé tan trong née, tan duigc trong acid va base do 6 tinh lung tinh (amin=NH, 6 tinh base, sulfamid= SO,NH, cé tinh acid) IL.2 Sic ki 16p méng: 2. Tai sao phdi lac silicagel trong 2 phut? - 6 silicagel dui thi gian trueng nd (do co nhiéu nhom —OH), néu som hon thi silicagel qua long > chay; néu lau hon thi qua dac ko trang dug. 3. Ngoai soi UV, cbn cach nao dinh tinh suifamid? Cé cach nao ko ding thuéc thiy soi UV van thé ko? ni hydrin dé nhan dién nhom amin. - PDAD: p- dimetylamino benzaldehyd Silicagel c6 trgn sn chat phat quang Ill. Thi tinh khiét: Hoi 1. Tai sao phai ding nv6c dun s6i dé ngudi dé pha dd A? Néu ko d& ngudi ma pha naay thi sao? - Vicé thir gidi han pH, nén phai loai CO; 06 trong nue, va céc khi khdc: NHs, HCl 06 trong phong thi nghigm bj nhiém vao nue gay sai s6 khi kiém gi6i han pH. (Ngoai ra, CO2 cdn tao tia vei kim loai nang, gay sai i - KhOng dé ngudi sé 6 thé tich va Sulfanilamid bj tan trong nue néng, sau khi loc xong, dé guéi sé két tinh lai lam sai léch cdc két qua thi nghiém sau do. 2. IV. Dinh wong: 1. Taisao 6 DTD tha 1 giot NaNO2 thi chi thi déi mau ngay lap tire? Tai sao cha dén diém twong dyong ni - NaNO; oxy héa KI = Vitrong dd cé acid, gap KI trén gidy sinh ra HI khdng ban, bj oxy héa bi khong khi thanh I>BAI 12: KIEM DINH INH (RIMIFON) 2 phan tng tong hop INH: 1 9 ° HNNH. FO Ont SAAN GS ONHNH, NA NYA 2. (S) ICHACH. Hy oO 4.NaoH.s |G" NH A CHEN NG? 2. HNNH, ‘S ° OCHA(CH.),CHs 1. Dinh tinh: LI Pw tgo phite v6i natri nitroprussiat: do nhém amin bac 2. 1.2. Pu tgo tia véi CuSO4 : 1.3 Pw tao tia véi vanilin : ‘Aidehyd pu véi amin cho ra baseship (imin) thung cé mau. Nén khi uéng INH phai uéng cach xa Vit B6. Do INH pu v6i dang piridoxan cua Vit. BE oH ; OH ° sl Ns co "> 6 5 yese g | +H9 Nig 4c N HC yellow precipitate IL. Thir tinh khiét: nue dun séi dé naudi? i166 ib han pH11.2. Hydrazin va tap chat lién quan: Sac ki lép mong 2. Cac tap chat lién quang khi kiém isoniazid la nhieng cht nhy thé nao? - La nhiing chat 06 n6i doi (phat hign = soi UV), va c6 nhém -NH, (phat hién = PDAB) 3._ Tai sao phai kiém tap hydrazin? Do hydrazin durgc sir dung trong qua trinh ting hgp INH 4._ Silicagel str dung trong sac ki lop méng la? Silicagel GF254: silicagel pha dao, phat quang bude song 254 nm. 5._Cé can phai chdm hét 5 ul lén ban sac ki ko? Tai sao? Cé, vi day Ia phép ban dinh long. cé so mau khi phun PDAB, khéng tinh Rf. 6. Cé mAy loai cht d6i chiéu? C6 may loa tap va cdch phat hién? 2 io chat ai chiéu Hydrazin va 0,2 ml dd thir (d6ng vai trd la chat d6i chi8u oa tap khdng phai l& Hydrazin néu 06) C6 2 loai tap: C6 ni doi, va cé nhém amin bac 1 C6 2 céch phat hién: © Soi UV > phat hién tap 06 ndi doi (nhan thom) © Phun PDAB > phat hién hydrazin va cdc chat c6 nhém amin bac 1. (PDAB = para dimethyl amino benzaldehyd) 7. Khi soi UV, nhin thay de it nhdt 66 may chat? [a chat gi? Phun PDAB truéc khi soi UV dc ko? Tai a0? ‘Thay duge it nhat 1 chat: INH & ca mau chudn va mau thi? (kh6ng thé thay vét hydrazin) Khéng duge, vi phun PDAB sé che mau cac vét tap chat lién quan do PDAB hp thu anh sang bue séng 254 nm > két qua la ban sc ki khong con phat quang dudi dén UV 254 nm > khong con nhin thay dc vét nao niva. IIL. Dinh long 8. Nguyén tac dinh Iwona? pu oxy héa kht. 1; oxy héa hydrazin 9. Vai trd NaHCOs? Thay NaHCOs = NazCOy dugc khong? Vai tro: Phan hy INH tao hydrazin © Tao méi truéng kiém dé lz oxy héa hydrazin. Khéng duge, vi NaHCO; cé tinh kiém yéu hon hydrazin, va pu oxy héa xay ra trong méi tréng kiém nhe. 10. Tai sao phai lam trong tdi? Tai sao phai cho HCI va phai cho tir tu? Dung chat gi thay thé dung dich 12 48 cho ra 12 mdi sinh? Vi iodid bj bién chat bdi anh sang thanh Ip. é trung hda NaHCO,, vi méi trong dinh lweng la acid Phaii cho tir tl’ vi HCI gp NaHCO; sinh ra CO, bay Ién sé cudng theo I thang hoa Kalli iodid va acid + iodat. Pp nay giup khac phuc nhuge diém |; dé bay hoi khién dinh Iuwgng khong chinh xac. 11. D8 xudt 2 pp dinh Ivong kh4c? Do UV Dinh Ivgng moi trudng khan, 12. Nhéing diém can Iwu ¥ khi dinh lwong? Luén gid lanh Thao téc nhanh Cho HTB gan DTD.