MC LC

Trang M u....3 Phn I: Tng quan ........................................................................... .4 1.1.Ngnh k thut ha hc4 1.2.Chuyn ngnh ha dc v ha cht bo v thc vt.5 Phn II: Thit k quy trnh tng hp Phenobarbital7 2.1. Tng quan v phenobarbital7 2.1.1.Tn.7 2.1.2.Tnh cht vt l.8 2.1.3.Tnh cht ha hc.8 2.1.4.Tc dng dc l..8 2.1.5.Tiu chun dc in..17 2.1.6.ng dng.19 2.2. Nhng phng php tng hp Phenobarbital...20 2.2.1. Phng php 1...20 2.2.2. Phng php 2...20 2.2.3. Phng php 3...20 2.2.4. Phng php 4...21 2.2.5. Phng php 5...22 2.2.6. Phng php 6...22 2.2.7. Phng php 7...23 2.2.8. Phng php 8...24 2.3. Quy trnh cng ngh la chn.25 2.3.1. C s l thuyt la chn25 2.3.2. xut quy trnh phn ng..27 2.3.2.1.Phng trnh phn ng..27 2.3.2.2. M t quy trnh phn ng27 2.3.2.3. S khi quy trnh.28 1
n nhp mn k thut ha hc

2.3.3. Tnh cht cha mt s nguyn liu tham gia vo qu trnh phn ng....29 Kt lun32 Ti liu tham kho...33

2
n nhp mn k thut ha hc

M U
Ha hc l ngnh khoa hc lu i v lun hp dn con ngi i su nghin cu. Vi vai tr l sinh vin ngnh ha,chng em lun lun hc hi cc vn lin quan hiu hn v ngnh cng nh chuyn ngnh ca mnh. n nhp mn k thut ha hc p ng vi nhu cu ca chng em , n mang li c hi tham gia, tm hiu mt cch tng quan v ngnh k thut ha hc cng nh chuyn ngnh ha dc & ha cht bo v thc vt, gip chng em bc u tip xc vi cch hc tp chuyn su hn. ti ca chng em l tm hiu quy trnh tng hp phenolbarbital. Phenobarbital c c tnh l thuc ng, thuc an thn v thi min rt ni ting vo nm 1912, nhng khng ai bit n cng l mt chng co git c hiu qu cho n khi Alfred Hauptmann nhn ra khi s dng cho cc bnh nhn ng kinh ca mnh.Do tc dng trn vo thi Phenobarbital c cung cp rng ri v -c sn xut trn qui m cng nghip. Tuy ngy nay do cc tc dng ph ,Phenobarbital khng c khuyn khch l thuc u tin s dng,nhng i khi n vn c s dng nh mt thuc gim au hay thuc ng bnh nhn lo lng hoc kch ng hoc nhng ngi mn cm vi benzodiazepin , v cc loi thuc an thn mi hn. Khng th khng ni rng Phenobarbital c ngha to ln trong y hc v trong ngnh cng nghip dc vi vai tr l thuc c hiu qu rng ri chng co git u tin v lu i nht cn c s dng n ngy nay.

3
n nhp mn k thut ha hc

Phn I . TNG QUAN :

1.1. NGNH K THUT HA HC : [1][6] Ha hc l khoa hc nghin cu v cht v phng php bin i cht. Ha hc ni v cc nguyn t, hp cht, nguyn t, phn t, v cc phn ng ha hc xy ra gia nhng thnh phn . S phi tn rt nhiu thi gian lit k tt c cc sn phm chu nh hng bi cc k s ha hc, nhng bit v nhng ngnh cng nghip s dng cc k s ha hc c th gip bn hiu c phm vi cng vic ca h. Ngi k s cng ngh ho c th lm trong rt nhiu lnh vc khc nhau nh: nghin cu c bn v ng dng cc qu trnh ho hc, pht trin sn phm, thit k, m phng, hiu chnh cc quy trnh cng ngh v thit b, thit k, m phng, iu hnh hot ng ca cc nh my; cng tc cc c quan chnh ph, nghin cu v ging dy ti cc trng i hc, cc vin nghin cu hoc c th tham gia vo cc lnh vc thng mi nh: kinh doanh, qun l, marketing, c vn, bn hng Trong nhng ngnh cng nghip,k s ha cht da vo kin thc v ton hc v khoa hc, c bit l ha hc, vt qua vn k thut an ton v kinh t. V, tt nhin, h bi din v p dng cc kin thc gii quyt bt k nhng thch thc k thut m h gp phi. ng mc phi sai lm khi ngh rng k s ha hc lm mi vic, mc d chuyn mn ca h cng c p dng trong lnh vc php lut,gio dc, xut bn, ti chnh, v y hc, cng nh nhiu lnh vc khc c yu cu o to k thut. V d: cc k s ha hc ci thin k thut ch bin thc phm, v phng php sn xut phn bn , tng s lng v cht lng ca thc phm c sn. H cng to nn cc si tng hp lm cho qun o ca chng ta thoi mi hn v c kh nng chu nc, h pht trin phng php sn xut i tr thuc, lm cho chng c gi c phi chng hn, h tng an ton v hiu qu cc ca cc phng php tinh ch sn phm du m, nng lng v cc ngun ha cht, lm tng sn xut v hiu qu chi ph hn. H cng pht trin cc gii php cho cc vn mi trng, chng hn nh khc phc v kim sot nhim,h pht trin ha cht, th thng c s dng lm tt c mi th m ta nhn thy xung quanh mnh. K s ha hc gp phi nhng thch thc tng t m cc chuyn gia 4
n nhp mn k thut ha hc

khc phi i mt,v h p ng c nhng thch thc p dng kin thc k thut, k nng giao tip v lm vic theo nhm,thc hnh kt hp v nhn thc cc thng tin mi nht hin c. Li ch t ngnh k thut ho hc bao gm li ch kinh t, s cng nhn trong ngnh cng vic v x hi, v nim vui c c t lm vic vi khoa hc t nhin p ng nhu cu ca x hi. nh hng : Theo S Lao ng Hoa K, Phng Lao ngThng k, k s ha hc c d kin s c vic lm tng trng 8 phn trm trong d on mi nm t 2006 n 2016. y l kh nhanh cho tt c cc ngh. Mc d vic lm tng th v ngnh cng nghip ha hc sn xut d kin s gim, cc cng ty ha cht s tip tc nghin cu v pht trin mi ha cht v hiu qu quy trnh tng sn lng hin c nhiu hn na. Trong s cc ngnh cng nghip sn xut, dc phm c th cung cp tt nht c hi cho ngi tm vic. Tuy nhin, hu ht tng trng vic lm cho cc k s ha hc l cung cp cho ngnh nh nghin cu khoa hc, v dch v k thut, c bit i vi nghin cu v nng lng v pht trin lnh vc cng ngh sinh hc, cng ngh nano,nng lng sinh hc v mi trng. 1.2. CHUYN NGNH HA DC & HA CHT BO V THC VT:[2] Ha dc theo nh ngha ca IUPAC l mt ngnh khoa hc da trn nn tng ha hc nghin cu cc vn ca cc ngnh khoa hc sinh hc, y hc v dc hc. Ha dc bao gm vic khm ph, pht minh, thit k, xc nh v tng hp cc cht c tc dng hot tnh sinh hc, nghin cu s chuyn ha, gii thch c ch tc ng ca chng mc phn t, xy dng cc mi quan h gia cu trc v tc dng sinh hc hay tc dng dc l (gi l SAR) v mi quan h nh lng gia cu trc v tc dng sinh hc hay tc dng dc l (gi l QSAR). Vai tr ca ho dc l nghin cu cu trc phn t ca hp cht v ci thin tnh cht cha bnh ca hp cht . y l s giao thoa ca ho hc (khoa hc v vt cht) v dc hc (khoa hc v hot tnh ca thuc), lin kt 5
n nhp mn k thut ha hc

cht ch gia tnh cht dc l v cu trc ha hc. Hu ht cc loi thuc hu c u c c lp t thin nhin, mt trong nhng nhim v quan trng c bn ca lnh vc ha dc l lm thay i cu trc ho hc ca hp cht theo hng mong mun, c th bng tng hp hu c. Cc nghin cu v ha dc bt u ngay sau khi qu trnh tng hp hu c c hon tt : ngha l tin hnh xong phn tng hp cc phn t mong mun, trong khi nhim v ca ha dc l kho st cc hot tnh ca cc phn t ny. Khi ni n vic kho st cc phn t thuc th ngi ta lun lun dng s nhiu, lun lun l cc hot tnh ch khng bao gi dng li s t mt hot tnh no do ha dc c tnh a ngnh rt ln. Bn yu t quan trng trong ngnh ha dc l dc lc hc, dc ng hc (PK-ADME), c tnh v tnh cht l-ho hc. Ho dc vi c im lin ngnh ca n lm cu ni kt hp ha hu c, ho phn tch, ha hc phc cht, vt l ... vi sinh l hc v y hc. L mt ngnh khoa hc c tnh c bn rt cao trong vic pht hin, nghin cu bn cht ca thuc v cc nghin cu c bn v ang pht trin rt mnh trong thp k qua. Ngy nay vi s hp tc ca cc nh khoa hc trn nhiu lnh vc a v ang tin hnh nghin cu v tm cc loi hp cht mi c kh nng chng ung th, HIV-AIDS, virus, v m ra nhng hi vng cho cc bnh nhn mc bnh him ngho. -Thc trng ngnh cng ngh ho dc : Phi tha nhn mt thc t l xt v quy m, ngnh cng nghip ho dc nc ta cn tng i nh b v ngho nn v chng loi sn phm, cha sn xut c cc nguyn liu ch yu nhm p ng nhu cu bo ch cc loi thuc. Theo s liu ca ngnh dc v B Y t th cc cng ty dc Vit Nam ch yu thc hin bo ch gia cng, cn hu nh cc nguyn liu ho dc u phi nhp khu t 80-85%. i ng nghin cu ho dc ngy cng mai mt v by gi mi bt u o to li.y thc s l nhng th thch ln i vi ngnh ho dc Vit nam c v ngun nhn lc cng nh hng nghin cu v pht trin, quy hoch ngun nguyn liu, c s vt cht k thut nhm phc v cho ngnh khoa hc trng im ny.

6
n nhp mn k thut ha hc

Trong khi , ngnh ho dc trn th gii c lch s pht trin lu di,t c nhng bc tin di v nhiu thnh tu to ln.Trong nhng nm gn y,ngnh cng ngh ha dc tr thnh ngnh khoa hc trng im nhiu quc gia nh M,Anh,Nht Bn v nhiu nc chu u khc,ng gp to ln vo nn kinh t quc dn v quan trng hn c l ngy mt nng cao vic chm sc sc khe i sng con ngi. -nh hng pht trin: Theo quy hoch pht trin ngnh cng nghip ho dc nc ta, giai on t nay n nm 2015 s tp trung u t nhng d n iu tra tng th ngun nguyn liu t nhin; nh my sn xut ho dc v c v t dc thng thng; nh my chit xut ho dc c ngun gc thin nhin v bn tng hp; nh my lin doanh t dc cao cp; nh my sn xut thuc khng sinh (giai on 1); nh my sn xut sorbitol Giai on 2016-2025 s tp trung vo cc loi thuc khng sinh; vitamin; thuc h nhit gim au; thuc tim mch, tiu ng, chng lao, chng st rt, mt tr nh, iu chnh th trng; thuc phng dch Tp trung vo cc d n u t nh m rng cng sut nh my sn xut sorbitol ln 20.000 tn/nm; xy dng nh my sn xut khng sinh giai on 2; u t xy dng nh my sn xut mt s thuc gim st, gim au chng vim thng dng nh paracetamol, aspirin; nh my sn xut vitamin C cng sut 1.000 tn/nm.

Phn II. THIT K QUY TRNH TNG HP PHENOBARBITAL :

2.1 .Tng quan v phenobarbital 2.1.1. Tn: -Tn chung: phenobarbital -Tn ring: Luminal Eskabarb Solfoton Talpheno -Tn khoa hc: 5-etyl-5-phenylpyrimidine-2, 4,6 (1 H, 3 H, 5 H)-trione hay: 7
n nhp mn k thut ha hc

5-Ethyl-5-phenyl-2, 4,6 (1 H ,3 H ,5 H )-pyrimidinetrione (1 H, 3 H, 5 H)-pyrimidinetrione -Cng thc: Cng thc phn t: Phn t khi: 2.1.2.tnh cht vt l: -Tinh th khng mu hay bt kt tinh trng , khng mi .V hi ng. - tan: Rt kho tan trong nc,xp x 1 g phenobarbital ha tan trong 1l nc, hi tan trong cloroform, tan trong ether, tan trong ethanol 96%, to thnh hp cht tan trong nc v hydroxyd , carbonat kim v amoniac. -im nng chy: 175-179c -pH: 5,0-6,0 (bo ha dung dch) -Nhp P: 1,47 (thc nghim xc nh gi tr) 1,36 (tnh ton gi tr) -ion ha lin tc pK a: 7.4 -im si: 138-140 (12 torr) 138-140 (12 Torr) -Mt : 1.352 g/cm3 1,352 g/cm3 2.1.3.Tnh cht ha hc: Phenobarbital tan trong NaOH v cc dung dch kim khc to mui tan
O HN O HN O Na C2H5
+ NaOH

C12H12N2O3 232,24

O HN O N O C2H5
+

H2O

2.1.4.Tc dng dc l:[2] Dc l v c ch tc dng: Phenobarbital l thuc chng co git thuc nhm cc barbiturat. Phenobarbital v cc barbiturat khc c tc dng tng cng v/ hoc bt chc tc dng c ch synap ca acid gama aminobutyric (GABA) no; iu ny cho thy chng c nhng im tng ng vi cc benzodiazepin. Tuy nhin, cc barbiturat khc vi cc benzodiazepin tnh chn lc km hn; vi cc barbiturat, ngoi tc dng c ch chn lc ln 8
n nhp mn k thut ha hc

synap, ch cn tng liu nh cng gy c ch khng chn lc. Phenobarbital v cc barbiturat khc lm gim s dng oxygen no trong lc gy m, c l ch yu thng qua vic c ch hot ng ca neuron. Cc tc dng ny l c s ca vic s dng cc barbiturat phng nhi mu no khi no b thiu mu cc b v khi tn thng s no. Cc barbiturat c ch c hi phc hot ng ca tt c cc m. Tuy vy, vi cng mt nng trong huyt tng hay vi cc liu tng ng, khng phi tt c cc m u b nh hng nh nhau. H thn kinh trung ng nhy cm vi cc barbiturat hn rt nhiu; liu thuc gy ng v an thn ch c tc dng khng ng k ln c xng, c tim v c trn. Phenobarbital c ch h thn kinh trung ng mi mc , t an thn n gy m. Thuc ch c ch tm thi cc p ng n synap h thn kinh trung ng, nhng s hi phc ca synap b chm li v c s gim tr khng sau synap mt s synap, cc p ng a synap b nh hng nhiu hn; iu ny gii thch v sao tc dng chng co git v tc dng c ch ca thuc li ko di. Phenobarbital ch yu c dng chng co git, tuy vy thuc vn cn phn no c dng iu tr hi chng cai ru. Tc dng chng co git ca thuc tng i khng chn lc; thuc hn ch cn ng kinh lan ta v lm tng ngng ng kinh. Thuc ch yu c ch nh trong cn ng kinh ton b (cn ln), v ng kinh cc b (cc b vn ng hoc cm gic). Phenobarbital lm gim nng bilirubin huyt thanh tr s sinh, ngi bnh tng bilirubin huyt khng lin hp, khng tan huyt bm sinh v ngi bnh mt trong gan, c th do cm ng glucuronyl transferase, mt enzym lin hp bilirubin. Thuc ung c hp thu chm ng tiu ha (80%), thuc gn vo protein huyt tng ( tr nh 60%, ngi ln 50%) v c phn b khp cc m, nht l no, do thuc d tan trong m. Th tch phn b l 0,5 - 1 lt/kg. Nng nh trong huyt tng t sau khi ung 8 - 12 gi ngi ln, sau 4 gi tr em v nng nh trong no t sau 10 - 15 gi. Na i ca thuc trong huyt tng di (2 - 6 ngy) v thay i theo tui: Tr em 9
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t 1 n 10 tui o thi phenobarbital nhanh hn nhiu so vi ngi ln (40 - 50 gi tr em; 84 - 160 gi ngi ln) cn ngi bnh b suy gan hoc suy thn th di hn rt nhiu. Phi sau 15 - 21 ngy mi t trng thi cn bng ng ca thuc. Thuc t hu mn hu nh c hp thu hon ton rut gi. Nu tim tnh mch, tc dng ca thuc xut hin trong vng 5 pht v t mc ti a trong vng 30 pht. Tim bp tht, tc dng xut hin chm hn mt cht. Dng theo ng tim, phenobarbital c tc dng ko di t 4 n 6 gi. Phenobarbital c hydroxyl ha v lin hp ha gan. Thuc o thi ch yu theo nc tiu di dng cc cht chuyn ha khng c hot tnh (70%) v dng thuc nguyn vn (30%); mt phn nh vo mt v o thi theo phn. Phenobarbital l cht cm ng cytochrom P450 mnh nn c nh hng n chuyn ha ca cc thuc c chuyn ha gan thng qua cytochrom P450. Tc dng: Chng co git v an thn, gy ng. Dng thuc v hm lng Vin nn 15 mg, 50 mg, 100 mg; dung dch tim 200 mg/1 ml; dung dch ung 15 mg/5 ml; vin n. Ch nh ng kinh (tr ng kinh cn nh): ng kinh cn ln, ng kinh git c, ng kinh cc b. Phng co git do st cao ti pht tr nh. Vng da s sinh, v ngi bnh mc chng tng bilirubin huyt khng lin hp bm sinh, khng tan huyt bm sinh v ngi bnh mt mn tnh trong gan. Chng ch nh Ngi bnh qu mn vi phenobarbital. Ngi bnh suy h hp nng, c kh th hoc tc nghn. Ngi bnh ri lon chuyn ha porphyrin. Suy gan nng. Thn trng Ngi bnh c tin s nghin ma ty, nghin ru. Ngi bnh suy 10
n nhp mn k thut ha hc

thn. Ngi bnh cao tui. Khng c ngng thuc t ngt ngi bnh mc ng kinh. Dng phenobarbital lu ngy c th gy l thuc thuc. Ngi mang thai v ngi cho con b (xem phn di). Ngi bnh b trm cm. -Thi k mang thai Phenobarbital qua nhau thai. Cc b m c iu tr bng phenobarbital c nguy c con b d tt bm sinh cao gp 2 - 3 ln so vi bnh thng. Dng phenobarbital ngi mang thai iu tr ng kinh c nguy c gy nhiu d tt bm sinh cho thai nhi (xut huyt lc ra i, ph thuc thuc). Nguy c d tt bm sinh cng cao, nu thuc vn c dng m khng ct c ng kinh. Trong trng hp ny, cn nhc gia li v hi, vn phi cho tip tc dng thuc nhng vi liu thp nht n mc c th kim sot cc cn ng kinh. Nu ngi m khng b ng kinh, nhng c dng phenobarbital trong thi k mang thai, nguy c v d tt t thy, nhng tai bin xut huyt v l thuc thuc tr s sinh cn l vn ng lo ngi. Chy mu tr s sinh cng ging nh chy mu do b thiu ht vitamin K v iu tr khi bng vitamin K. phng chy mu lin quan n thiu ht vitamin K, cn b sung vitamin K cho m (tim 10 - 20 mg/ngy) trong thng cui cng ca thai k v cho tr s sinh (tim 1 4 mg/ngy trong 1 tun). tr s sinh c m dng barbiturat trong sut ba thng cui thai k c th c triu chng cai thuc. Cn theo di cht ch cc du hiu suy h hp tr s sinh m m dng phenobarbital lc chuyn d v nu cn th phi iu tr ngay ng c thuc phenobacbital qu liu. Tr thiu thng rt nhy cm vi tc dng c ch ca phenobarbital, nn phi rt thn trng khi dng thuc trong trng hp d bo non. -Thi k cho con b Phenobarbital c bi tit vo sa m. Do s o thi thuc tr b m chm hn, nn thuc c th tch t n mc nng thuc trong mu tr c th cao hn ngi m v gy an thn cho tr. Phi tht thn trng khi bt buc phi dng phenobarbital cho ngi cho con b. Phi dn cc b m cho con b m ung phenobarbital, nht l vi liu 11
n nhp mn k thut ha hc

cao, ch theo di con mnh xem c b tc dng c ch ca thuc hay khng. Cng nn theo di nng phenobarbital tr trnh mc gy c. Tc dng khng mong mun (ADR) Thng gp, ADR >1/100 Ton thn: Bun ng. Mu: C hng cu khng l trong mu ngoi vi. Thn kinh: Rung git nhn cu, mt iu ha ng tc, lo hi, b kch thch, l ln ( ngi bnh cao tui). Da: Ni mn do d ng (hay gp ngi bnh tr tui). t gp, 1/1000 < ADR < 1/100 C - xng: Ci xng, nhuyn xng, lon dng au c (gp tr em khong 1 nm sau khi iu tr), au khp. Chuyn ha: Ri lon chuyn ha porphyrin. Da: Hi chng Lyell (c th t vong). Him gp, ADR <1/1000 Mu: Thiu mu hng cu khng l do thiu ht acid folic. Hng dn cch x tr ADR Phi gim liu phenobarbital ngi bnh cao tui, ngi bnh c tin s bnh gan hay bnh thn. Nu tim phenobarbital vo tnh mch th phi tim tht chm (di 60 mg/pht). Tim qu nhanh c th gy c ch h hp. Cn dnh ng tim tnh mch cho cp cu trng thi ng kinh cp, ch nn tin hnh ti bnh vin v theo di tht cht ch. Khi c bt c tc dng ph no phi ngng dng phenobarbital ngay. Do tc dng cm ng ca phenobarbital ln cytochrom P450, nng trong huyt tng ca vitamin D2 v D3 (v c calci), ngi bnh c iu tr chng co git liu cao, di ngy, c th b gim thp. Ngi bnh iu tr bng phenobarbital phi c b sung vitamin D ( tr em 1200 - 2000 vqt mi ngy) v acid folic phng bnh ci xng v nhuyn xng do dng thuc chng co git. Liu lng v cch dng Cch dng Phenobarbital c th ung, tim di da, tim bp su v tim tnh 12
n nhp mn k thut ha hc

mch chm. ng tim di da gy kch ng m ti ch, khng c khuyn co. Tim tnh mch c dnh cho iu tr cp cu cc trng thi co git cp, tuy vy tc dng ca thuc cng b hn ch trong cc trng hp ny (thuc c la chn trong trng thi ng kinh l diazepam hoc lorazepam). Khi tim tnh mch, ngi bnh phi nm bnh vin v c theo di cht ch. Thuc phi tim chm vo tnh mch, tc khng qu 60 mg/pht. tim di da hoc tim bp, 120 mg bt natri phenobarbital khan c ha tan trong 1 ml nc ct pha tim v khun. tim tnh mch, 120 mg bt natri phenobarbital khan cn c ha tan trong 3 ml nc ct pha tim v khun. Nu dng di ngy, phi gim liu phenobarbital dn dn trnh cc triu chng cai thuc khi ngi bnh nghin. Khi chuyn sang dng thuc chng co git khc, phi gim liu phenobarbital dn dn trong khong 1 tun, ng thi bt u dng thuc thay th vi liu thp. Liu lng Liu lng ty thuc tng ngi bnh. Nng phenobarbital huyt tng 10 microgam/ml gy an thn v nng 40 microgam/ml gy ng a s ngi bnh. Nng phenobarbital huyt tng ln hn 50 microgam/ml c th gy hn m v nng vt qu 80 microgam/ml c kh nng gy t vong. Tng liu dng hng ngy khng c vt qu 600 mg. ng ung (tnh theo phenobarbital base): Liu thng thng ngi ln: Chng co git: 60 - 250 mg mi ngy, ung 1 ln hoc chia thnh liu nh. An thn: Ban ngy 30 - 120 mg, chia lm 2 hoc 3 ln mi ngy. Gy ng: 100 - 320 mg, ung lc i ng. Khng c dng qu 2 tun iu tr mt ng. Chng tng bilirubin huyt: 30 - 60 mg, 3 ln mi ngy. Liu thng thng tr em: Chng co git: 1 - 6 mg/kg/ngy, ung 1 ln hoc chia nh liu. An thn: Ban ngy 2 mg/kg, 3 ln mi ngy. 13
n nhp mn k thut ha hc

Trc khi phu thut: 1 - 3 mg/kg. Chng tng bilirubin - huyt: S sinh: 5 - 10 mg/kg/ngy, trong vi ngy u khi mi sinh. Tr em ti 12 tui: 1 - 4 mg/kg, 3 ln mi ngy. ng tim: (tim bp su hoc tim tnh mch). Liu thng thng ngi ln: Chng co git: 100 - 320 mg, lp li nu cn cho ti tng liu 600 mg/24 gi Trng thi ng kinh: Tim tnh mch 10 - 20 mg/kg, lp li nu cn. An thn: Ban ngy, 30 - 120 mg/ngy, chia lm 2 hoc 3 ln. Trc khi phu thut: 130 - 200 mg, 60 n 90 pht trc khi phu thut. Gy ng: 100 - 325 mg. Liu thng thng tr em: Chng co git: Liu ban u: 10 - 20 mg/kg, tim 1 ln (liu tn cng hoc liu np). Liu duy tr: 1 - 6 mg/kg/ngy. Trng thi ng kinh: Tim tnh mch chm (10 - 15 pht) 15 - 20 mg/kg. An thn: 1 - 3 mg/kg, 60 - 90 pht trc khi phu thut. Chng tng bilirubin huyt: 5 - 10 mg/kg/ngy, trong vi ngy u sau khi sinh. Ghi ch: Ngi bnh cao tui v suy nhc c th b kch thch, l ln hoc trm cm vi liu thng thng. nhng ngi bnh ny c th phi gim liu. Tng tc thuc -Phenobarbital l cht cm ng mnh cytochrom P450 enzym tham gia trong chuyn ha ca rt nhiu thuc. -Phenobarbital lm gim nng ca felodipin v nimodipin trong huyt tng. Cn xem xt chn la mt thuc chng tng huyt p khc hay mt thuc chng ng kinh khc. -Phenobarbital c th lm mt tc dng ca thuc trnh thai theo ng ung, khi c dng ng thi, do lm tng chuyn ha gan. 14
n nhp mn k thut ha hc

Cn p dng bin php trnh thai khc; nn chn bin php c hc. -Phenobarbital v doxycyclin dng ng thi: Na i ca doxycyclin ngn li, khin nng doxycyclin trong huyt tng gim. Cn tng liu doxycyclin hoc chia ung ngy hai ln. - Phenobarbital v corticoid dng ton thn: Phenobarbital lm gim tc dng ca cc corticoid. Cn ch iu ny, c bit ngi mc bnh Addison v ngi bnh c ghp tng. -Phenobarbital v ciclosporin: Nng trong huyt tng v tc dng ca ciclosporin b gim khi c mt phenobarbital. Cn tng liu ciclosporin trong khi iu tr bng phenobarbital v cn gim liu ciclosporin khi thi dng phenobarbital. -Phenobarbital v hydroquinidin v quinidin: Nng trong huyt tng v tc dng chng lon nhp ca quinidin b gim. Cn theo di lm sng, in tim, nng quinidin trong mu. Cn iu chnh liu quinidin. Phenobarbital v levothyroxin: Ngi bnh c tin s gim chc nng gip c nguy c b suy gip. Phi kim tra nng T3 v T4. Phi chnh liu levothyroxin trong v sau tr liu bng phenobarbital. -Phenobarbital v acid folic: Nng phenobarbital trong huyt tng gim c th lm gim tc dng ca acid folic. Phi iu chnh liu phenobarbital khi dng b sung acid folic. -Phenobarbital v theophylin: Nng trong huyt tng v tc dng ca theophylin b gim. Cn iu chnh liu theophylin trong khi iu tr bng phenobarbital. -Phenobarbital v cc thuc chng trm cm ba vng: Cc thuc chng trm cm loi imipramin c th lm tng nguy c xut hin cc cn co git ton thn. Cn phi tng liu cc thuc chng ng kinh. Phenobarbital v acid valproic: Nng trong huyt tng v tc dng an thn ca phenobarbital tng ln. Cn gim liu phenobarbital khi c du hiu tm thn b c ch. -Phenobarbital v cc thuc chng ng dng ng ung: Tc dng ca thuc chng ng b gim. Phi thng xuyn kim tra prothrombin huyt. Cn iu chnh liu thuc chng ng trong khi iu tr bng phenobarbital v trong 8 ngy sau khi ngng dng 15
n nhp mn k thut ha hc

phenobarbital. -Phenobarbital v digitoxin: Tc dng ca digitoxin b gim. -Phenobarbital v disopyramid: Tc dng chng lon nhp ca disopyramid gim do nng disopyramid trong huyt tng b gim. Phi iu chnh liu disopyramid. -Phenobarbital v progabid: Nng trong huyt tng ca phenobarbital tng. -Phenobarbital v carbamazepin: Nng trong huyt tng ca carbamazepin gim dn nhng khng lm gim tc dng chng ng kinh. -Phenobarbital v cc thuc trm cm khc, thuc khng H1, benzodiazepin, clonidin, dn xut ca morphin, cc thuc an thn kinh, thuc gii lo...: lm tng tc dng c ch h thn kinh trung ng. -Phenobarbital v phenytoin: Nng trong huyt tng ca phenytoin thay i bt thng. Cc triu chng ng c phenytoin c th xy ra khi ngng dng phenobarbital. Khi ng thi dng phenytoin th nng phenobarbital trong mu c th tng ln n mc ng c. -Phenobarbital v cc thuc chn beta (alprenolol, metoprolol, propranolol): Nng trong huyt tng v tc dng lm sng ca cc thuc chn beta b gim. -Phenobarbital v methotrexat: c tnh v huyt hc ca methotrexat tng do dihydrofolat reductase b c ch mnh hn. -Phenobarbital v ru: Ru lm tng tc dng an thn ca phenobarbital v c th gy hu qu nguy him. Phi trnh dng ru khi s dng thuc. n nh v bo qun Dung dch natri phenobarbital trong nc ni chung khng bn vng. Thuc trong polyethylen glycol hoc propylen glycol th bn vng hn. Khng c dng dung dch tim nu c ta. Trnh cc ng thuc tim tnh mch ra nh sng. Tng k Cc dung dch natri phenobarbital khng c dng ln vi cc dung 16
n nhp mn k thut ha hc

dch acid v c th lm ta phenobarbital. Cc dung dch phenobarbital tim khng ph hp v mt vt l v/hay ha hc vi nhiu thuc khc. Qu liu v x tr Liu gy c ca cc barbiturat rt dao ng. Ni chung, phn ng nng xy ra khi lng thuc ung vo nhiu hn liu thng dng gy ng 10 ln. T vong thng xy ra khi nng phenobarbital trong mu cao hn 80 microgam /ml. Khi ung qu liu barbiturat, h thn kinh trung ng b c ch t mc ng n hn m su ri t vong; h hp b c ch c th n mc c nhp th Cheyne - Stockes, gim thng kh trung tm v tm ti; gim thn nhit ri st, mt phn x, tim nhanh, huyt p tt, thiu niu. ng t thng hi co nhng nu ng c nng th li gin. Ngi bnh b qu liu nng thng c hi chng chong in hnh: Th chm, try mch, ngng h hp, v c th t vong. Cc bin chng vim phi, ph phi, suy thn c th gy t vong. Cc bin chng khc nh suy tim sung huyt, lon nhp tim, nhim khun ng tit niu cng c th xy ra. Phi iu tr v theo di ngi bnh ti khoa cp cu. iu tr qu liu ch yu l iu tr h tr, nht l gip cho ng th thng v nu cn thit th h hp vin tr v cho th oxy. Cch iu tr c a dng nht trong cp cu ng c phenobarbital l dng nhiu liu than hot, a vo d dy qua ng thng ng mi. Than hot lm tng o thi thuc v rt ngn thi gian hn m. Khng nn ra d dy hoc ht d dy tr khi chc chn l thuc mi c ung (trong vng 4 gi); cn ch khng ngi bnh ht vo phi cc cht cha trong d dy. Nu ngi bnh c chc nng thn bnh thng th c th gy li niu v kim ha nc tiu lm tng o thi phenobarbital qua thn. Nu ngi bnh b ng c nng, v niu hay b sc th nn thm phn phc mc hay lc mu thn nhn to. Thng tin qui ch Phenobarbital c trong danh mc thuc thit yu Vit Nam ban hnh ln th t nm 1999. 17
n nhp mn k thut ha hc

Thuc hng tm thn. 2.1.5.Tiu chun dc in:[4] C12H12N2O3 P.t.l: 232,2 Phenobarbital l acid 5- ethyl - 5 - phenylbarbituric, phi cha t 99,0 n 101,0% C12H12N2O3, tnh theo ch phm lm kh. nh tnh C th chn mt trong hai nhm nh tnh sau: Nhm I: A v B. Nhm II: B,C v D. A. Xc nh im chy (Ph lc 5.19) ca ch phm v ca hn hp ng lng ch phm vi phenobarbital chun. im chy ca ch phm v ca hn hp phi khong 176oC. S khc bit v im chy ca 2 mu trn khng c qu 2oC. B. Ph hng ngoi (Ph lc 3.2) ca ch phm phi ph hp vi ph hngngoi ca phenobarbital chun. C. Phng php sc k lp mng (Ph lc 4.4). Bn mng: Silicagel GF254. Dung mi khai trin: l lp di ca hn hp gm Amoniac m c ethanol 96% - cloroform (5: 15: 80). Dung dch th: Ho tan 0,1 g ch phm trong ethanol 96% (TT) c 100 ml. Dung dch i chiu: Ho tan 0,1 g phenobarbital chun trong ethanol96% (TT) c 100 ml. Cch tin hnh: Chm ring bit ln bn mng 10 l mi dung dch trn. Trin khai sc k ti khi dung mi i c khong 18 cm. Quan st ngay bn mng di nh sng t ngoi bc sng 254 nm. Vt chnh ca sc k thu c t dung dch th phi ging nhau v v tr v kch thc vi vt chnh ca sc k thu c t dung dch i chiu. D. Phn ng c trng ca barbiturat c hydro nhm NH khng b thay th (Ph lc 7.1). trong v mu sc ca dung dch Ho tan 1,0 g ch phm trong hn hp gm 4 ml dung dch natri hydroxyd

18
n nhp mn k thut ha hc

2 M v 6 ml nc. Dung dch phi trong (Ph lc 5.12) v mu khng c m hn mu mu V6 (Ph lc 5.17, phng php 2). Gii hn acid un si 1,0 g ch phm vi 50 ml nc trong 2 pht, ngui ri lc. Thm 0,15 ml dung dch methyl (CT) vo 10,0 ml dch lc, dung dch c mu vng cam. chuyn sang mu vng, th tch dung dch natri hydroxyd 0,1 N sdng khng c qu 0,1 ml. Tp cht lin quan Khng c qu 0,5%. Xc nh bng phng php sc k lp mng (Ph lc 4.4). Bn mng: Silicagel GF254. Dung mi khai trin: L lp di ca hn hp gm Amoniac m c ethanol 96% - cloroform (5: 15: 80). Dung dch th: Ho tan 1,0 g ch phm trong ethanol 96% (TT) v pha long n 100 ml bng cng dung mi. Dung dch i chiu: Pha long 0,5 ml dung dch th thnh 100 ml bng ethanol 96% (TT). Cch tin hnh: Chm ring bit ln bn mng 20 l mi dung dch trn. Trin khai sc k ti khi dung mi i c khong 15 cm. Quan st ngay bn mng di nh sng t ngoi bc sng 254 nm, phun thuc th diphenylcarbazon thu ngn (TT). kh bn mng ngoi khng kh, phun dung dch kali hydroxyd trong ethanol (TT) va mi pha. Sy bn mng 100 105oC trong 5 pht, quan st ngay tc khc. Khi quan st di nh sng t ngoi hoc sau khi phun thuc th, bt c vt ph no trn sc k thu c t dung dch th khng c m mu hn vt trn sc k thu c t dung dch i chiu. Mt khi lng do lm kh Khng c qu 1,0% (Ph lc 5.16). (1,000 g; 100 - 105oC; 2 gi). Tro sulfat Khng c qu 0,1% (Ph lc 7.7, phng php 2). 19
n nhp mn k thut ha hc

Dng 1,0 g ch phm. nh lng Ho tan 0,100 g ch phm trong 5 ml pyridin (TT), thm 0,5 ml dung dch thymolphtalein (CT) v 10 ml dung dch bc nitrat 8,5% trong pyridin. Chun bng dung dch natri hydroxyd 0,1 N trong ethanol n khi c mu xanh. Song song lm mu trng. 1 ml dung dch natri hydroxyd 0,1 N trong ethanol tng ng vi 11,61 mg C12H12N2O3. Bo qun Trong chai l kn. Ch phm Cn thuc phenobarbital. Vin nn phenobarbital. Tc dng v cng dng An thn, chng co git. 2.1.6. ng Dng:[5] Phenobarbital ch yu c dng chng co git, tuy vy thuc vn cn phn no c dng iu tr hi chng cai ru. Tc dng chng co git ca thuc tng i khng chn lc; thuc hn ch cn ng kinh lan ta v lm tng ngng ng kinh. Thuc ch yu c ch nh trong cn ng kinh ton b (cn ln), v ng kinh cc b (cc b vn ng hoc cm gic). iu tr vng da s sinh, chng tng bilirubin huyt khng lin hp bm sinh, khng tan huyt bm sinh v ngi bnh mt mn tnh trong gan.

2.2 NHNG PHNG PHP TNG HP PHENOBARBITAL [7] 2.2.1 Phng php th nht : phenyletylmalonicesterdiethyl d phn ng vi ure trong mi trng ca ethoxidenatri.

20
n nhp mn k thut ha hc

O Ar

O Ar OEt
H2N

Et

O O
OEt H2N

NaOEt

Et

NH

N H

2.2.2 Phng php th hai: Trong phng php th hai, phn ng cng tng t nh phng php u tin nhng natrimetoxit c s dng thay v ethoxide natri.

O Ar

O Ar OEt
H2N NH

Et

O O
OEt H2N

NaOMe

Et

N H

2.2.3 phng php th ba: Trong phng php th ba, malonate c ankyl ha hai ln trong mi trng c bn . TrongLn u tin, malonate c alkyl ho vi clorua etyl, v trong ln th hai n c alkyl ho vi clorua phenyl. xy ra phn ng ethylphenylmalonate vi guanidine v cyclization xy , sau nhm imino c thy phn tr thnh oxy v phenobarbital c to thnh .

21
n nhp mn k thut ha hc

O Et OEt EtCl Base

H

Cl

OEt

OEt

O Et
Ar

O NH2

OEt

Ar NH Et
N H NH

OEt

NH2 NaOEt

OEt

O O

NH

Ar H3O Et O
N H NH

2.2.4 phng php th t: Trong phng php th t, ethylphenylmalonate c tng hp nh trong phng php th ba. Tip l phn ng ca cyanoguanidine v decarboxyl-ated, c thy phn, kt qu to ra phenobarbital.

22
n nhp mn k thut ha hc

Cl O Et OEt EtCl O CN NH NH NH2 NaOEt O N H NH Ar CN Et N H2O Et CO2 O N H O NH OEt O O Ar OEt O OEt O

Base

2.2.5 phng php th nm: Trong phng php th nm, ethylphenylmalonate phn ng vi diethyloxalate tong mi trng ca ethoxide natri v acid sulfuric. Cc sn phm ethylphenyloacetate c nung nng 175 C v iu kin ny c gi cho n khi carbon monoxide hon ton ht, ta thu c diethylphenylmalonate v c alky-lated vi ethyliodide trong mi trng ca ethoxide natri. Cc sn phm phn ng l diethyl ethylphenylmalonate phn ng vi ur trong mi trng ca ethoxide natri. Phn ng cyclization din ra, ngng t ta c phenobarbital.

23
n nhp mn k thut ha hc

Ar

CH2 EtO2C-CO2Et

Et H

Ar-CH-CO-CO2Et nhit CO2Et

CO2 Et Ar-CH-CO2Et Ar Et I NaOEt CO2Et O NH2 NH2 NaOEt O Et N H O Ar CO2Et Et C-CO2Et

NH

2.2.6 phng php th su: Trong phng php th su, phn ng Knovenagel c s dng bi ngng t cyclohexa-none vi cyanoacetat v olefinic trung gian c to thnh. Sau n c alkyl ho vi ethyl halogen v c c c vi ur hoc cyanoguanidine. Cc sn phm A lhydrohysed v decarboxylated. Phenobarbital l sn phm cui cng. .
O O CN OEt O
CN O

OEt
NH Ar O

OEt

CN

Et CN NH

CN NH

Ar Et NH N CN

EtX
OEt O Ar

NH2

O san pham a

OH H2O

Et

NH

N H

24
n nhp mn k thut ha hc

: 2.2.7 phng php th by: Trong phng php th by phenylacetonitrile c cho phn ng vi diethylcacbonate trong mi trng ca natri v sau gia idoethane v natri kim loi c b sung vo hn hp phn ng. Ta thu c sn phm B , tip l phn ng ca B vi ur trong mi trng ca ethoxide natri v phn ng cyclization din ra dn n to ra sn phm c. C c thy phn bng acid HCl. Sn phm cui cng c to ra l Phenobarbital.

CN

Ar
CN

OEt O OEt

NaNH2

OEt

NH
Et

Ar
H2N CNH

Ar NH

EtI Na

O
OEt

O NH2

OEt

Et O
N H O

product B

productC Ar Et O
N H O NH

2.2.8 phng php th tm: Trong phng php th tm, phenylacetonitrile phn ng vi este ethyloxalate, sau ta cho phn ng vi etaliotdua trong mi trng kim loi Na. ta thu c sn phm D v Dc un nng xy ra phn ng decarboxylation v ta thu c sn phm E. E c c c vi ur trong mi trng ca ethoxide natri. Ngng t v phn ng cyclization din ra 25
n nhp mn k thut ha hc

ta thu c F, thy phn F bi acid hydrochlohidric ta thu c Phenobarbital.

H
OEt O CN Ar

O OEt
H Ar

CN EtI

O
tO CO2
O Et

OEt

O Na
CN H2N

Ar O
OEt

O H2N O

OEt NH san pham E

CN

san pham D Ar NaOEt Et

RA

NH

H \H2O

NH

Et
O N H

N H

san pham F

2.3 .QUY TRNH CNG NGH LA CHN: 2.3.1 c s l thuyt la chn Bng 1: hiu sut tng hp Phenobarbital(%) Loi v phng nng php th sut(%) nghim Nng sut(%) 1 recystallization 0.54 Nng sut(%) 2 recystallization Tng (%) s

Th nghim

1 Ln nht

Phng php 1

15.84

0.54

th Phng 1.66 php 2,

26
n nhp mn k thut ha hc

loi 1 Ln hai Ln nht Ln hai th Phng 1.36 php2, loi 1 th Phng 13.02 php 2, loi2 th Phng 22.48 php 2, loi 2 1.02 1.02

6.9

2.81

9.71

14.52

2.93

17.45

Bng 2: . Rf-Gi tr tiu chun v tng hp Phenobarbital (t phng php th hai , loi 2) Th nghim Std phenobarbital Ln th nht Ln th hai 0.56, 0.55 0.54, 0.56 Gi tr quang ph hng ngoi Tong hp phenobarbital 0.53, 0.57 0.55, 0.56

Bng 3: im nng chy ca Std Phenobarbita v tng hp Phenobarbita (t phng php 2, loi 2 ). Th nghim Ln th nht Ln th hai Ln th ba Std phenobarbital 172.3- 174.3 171.2-173.5 171.4-173.5 Tng hp phenobarbital 172.0- 172.5 171.3-172.5 170.3-171.7

Trn y l tm phng php tng hp phenobarbital.C hai phng php c nghin cu. Phng php u tin da trn phn ng ca ethylphenylmalonate diethyl v ur trong s c mt ca ethoxide natri (bng cch thm 1 / 2, 1 / 4, 1 / 8 v 1 / 8 phn ca ethoxide natri cho gi u tin th hai, th ba v th t, tng ng). Phng php th hai l da trn phn ng ca ethylphenylmalonatediethyl v ur trong s c mt ca metoxit 27
n nhp mn k thut ha hc

natri. Phng php ny c chia thnh hai loi. Loi u tin; : ethylphenylmalonate c b sung vo metoxit natri v sau b sung ur. i vi loi th hai; ur c b sung vo metoxit natri v cui cng ethylphenylmalonate diethyl c thm vo. S tng hp ca phenobarbital, s dng phng php th hai, cho nng sut t l phn trm cao nht (17,45%). Cc phenobarbital tng hp c xc nh bng cch s dng 3 k thut, sc k lp mng, quang ph tia hng ngoi v xc nh im nng chy. 2.3.2 xut quy trnh phn ng Da vo c s l thuyt trn, em s la chn phng php 2, loi 2 xy dng quy trnh sn xut. 2.3.2.1 phng trnh phn ng
Cl O

O Et OEt EtCl Base

H OEt

OEt

OEt

O
O Ar H2N

Ar OEt
NH

Et H2N

Et

O
OEt

NaOMe O
N H

2C2H5OH O

2.3.2.2 .m t quy trnh phn ng Cho urea kh v metoxitnatri vo ni phn ng ngng t khuy u. Nung n nhit si, sau tip tc cho ethylphenylmalonate vo ni khuy u, gi nhit si, kt hp khuy trn, trong qu trnh ny ru etylic sinh ra c a ra ngoi v ngng t. Sau mt thi gian a, hn hp ra , h nhit n nhit nh hn o C sau cho vo hn hp dung dch HCl c. tip ta lc vy ly tm ra trong nc lnh. Sau d ha tan ty mu nhit si, lc nng thu kt tinh, cho lc kt tinh trong nc lnh 28
n nhp mn k thut ha hc

bng phng php li tm sau sy kh trong chn khng ta c Phenobarbital nguyn cht vi tinh khit cao 2.3.2.3 .S khi ca quy trnh:

Ct loi cn Nhit si < 00C N-c ci

Ng-ng t ur Tinh ch Lc vy ly tm, ra

Ur kh+

NaOCH3

phenyletylmalonicest erdiethyl Lm HCl c + lnh H2O N-c lnh T0 si

Ho tan, ty mu B than Lc nng Kt tinh N-c ci Lc vy ly tm, ra Sy kh chn khng

N-c Than hot

N-c lnh

Sn phm cui cng c to ra l phenobarbital

29
n nhp mn k thut ha hc

2.3.3 tnh cht ca mt s nguyn liu tham gia vo qu trnh phn ng Ure [8] Cng thc:
NH2 H2N O

urea

a) Tnh cht ho hc: Nhiu kin tn thnh vi nghin cu ca Werner v cng thc dng vng v dng enol tn ti trong thi gian ngn ca ur nh- sau:
NH3

HN:C
O NH2

HN:C
OH

Tuy nhin, da vo nhng nghin cu ca Walker v Wood cho bit rng ur l mt baz yu v n khng c tnh cht axit. Ti p sut kh quyn v ti nhit nng chy ca ur n phn hu thnh amoniac, biur HN(CONH2), axit cyanuric C3N3(OH)3, ammelide NH2C3(OH)2, V triur NH2(CONH)2CONH2. Biur l thnh phn chnh v ng-i ta mong mun n c mt cng t cng tt trong ur tng hp bn trn th tr-ng. L-ng biur c mt trong cc sn phm phn bn ur nhiu hn 2% v khi l-ng rt c hi cho s pht trin ca cy. Ur hot ng nh- mt baz n v hnh thnh dng mui vi axit. Vi axit nitric n hnh thnh dng ur nitrat, CO(NH2).HNO3, Cht ny b phn hu rt mnh khi un nng:

CO(NH2)2

HNO3

CO(NH2)2.HNO3

Ur rn kh bn vng nhit phng v p sut kh quyn. Gia nhit trong chn khng nhit nng chy, ur thng hoa m khng thay i cu trc. Trong chn khng, ti nhit 180-1900C, ur 30
n nhp mn k thut ha hc

s thng hoa v b chuyn thnh amoni cyanat, NH4OCN. Khi ur rn -c un nng nhanh trong dng kh amonic ti nhit cao v p sut vi atm n thng hoa hon ton v bin i mt phn thnh axit cyanic, NHCO, v amoni cyanat. Ur lng cng c th ho tan trong amonic lng v hnh thnh dng hp cht c trng thi rt khng bn ur-ammonia,CO(NH2)2NH3, cht m b phn hu nhit trn 450C. Ur-ammonia phn ng vi kim loi kim hnh thnh dng mui nh- NH2CONHM hoc CO(NHM)2. Dung dch ur trong n-c b thu phn chm thnh amonic cacbamat ti nhit phng hoc ti nhit si ca n. Vt ca cyanat -c tm thy trong dung dch. un nng ur trong n-c thi gian di l nguyn nhn to thnh dng biur:
2NH2CONH2 NH2CONHCONH2 + NH3

Phn ng ny -c tin hnh p sut thp, nhit cao, v thi gian un nng di. Ti p sut 100200 atm, biur s chuyn tr li thnh ur vi s c mt ca amonic. Ur phn ng vi bc nitrat, AgNO3 vi s c mt ca natri hyrxyt, NaOH, to thnh dn xut diargentic, CON2H2Ag2, c mu vng nht. NaOH xc tc bin i ur thnh dng HNC(NH2)OH, cht phn ng AgNO3. Nhng tc nhn oxy ho trong s c mt ca NaOH chuyn ur thnh kh nit v cacbon dioxit. Sau cht ny li phn ng vi NaOH to thnh natri cacbonat.
NH2CONH2 + 3NaBr + 2NaOH N2 + 3NaBr + Na2CO3 + 3H2O

Phn ng ca ur vi r-u to thnh este ca axit cacbanic, thng th-ng gi l urtan.

NH2CONH2 + ROH NH2COOR + NH3

Ur phn ng vi formandehyt v cc dng hp cht nh- monometylolur, NH2CONHCH2OH, dimetylolur, v cc cht khc, ph thuc vo t l mol ca formandehyt vi ur v ph thuc vo pH ca dung dch. Ur phn ng vi hir peroxyt to thnh ur peroxyt, CO(NH2)2H2O2, L tinh th mu trng. N 31
n nhp mn k thut ha hc

-c bit n d-i ci tn th-ng mi l Hyperol, v th-ng -c dng lm tc nhn oxy ho. Dn xut ca ur -c dng trong d-c phm lm thuc ng, thuc an thn, gim au. Hp cht c bn ca nhng dn xut ny -c tng hp l axit bacbituric. C -c t phn ng ca ur v axit malonic ( chnh xc hn l t cc este ca n ).

COOH
CH2
+

NH2
CO NH2

HN OC HN

CO CH2 CO
+ H2O

COOH

b) Tnh cht vt l [15,696]: Ur l tinh th khng mu, hnh lng tr. Nhit nng chy 132,70C. Kh nng ho tan: tan trong n-c, r-u etlyic v tan t trong te. c) Ph-ng php iu ch: Tt c cc ph-ng php tng hp ur hin i u da trn nguyn tc ca phn ng gia amonic v cacbon dioxit trong l phn ng c p sut v nhit cao hnh thnh amoni cacbamat, v ng thi qu trnh hirat ho amoni cacbamat to thnh ur:
2NH3 + CO2 NH2COONH4 NH2COONH4 NH2COONH2 + H2O (phn ng 1) (phn ng 2)

Phn ng 1 l phn ng to nhit mnh. Nhit ca phn ng , tnh t amonic v cacbon dioxit 250C v p sut kh quyn, vo khong 38000 cal/g mol ca cacbamat rn to thnh 250C. Tc v trng thi cn bng ca phn ng 1 ph thuc phn ln vo p sut v nhit , v n c s thay i ln v th tch. Hoc ng-c li, phn ng ny c th ch xy ra ti nhit m thp hn p sut phn ly ca amoni cacbamat, p sut tin hnh trong l phn ng phi -c duy tr bn trn p sut bay hi ca cacbamat ti nhit tin hnh -c -a ra. Phn ng 2 to nhit vo khong 7500 cal/g mol ur to thnh.

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n nhp mn k thut ha hc

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n nhp mn k thut ha hc

KT LUN
Sau hai tun lm vic ht sc tp trung di s hng dn tn tnh ca c gio Nguyn Thy M. Nhm chng em d thu hoch c rt nhiu kin thc b ch: Nhng kin thc tng quan v ngnh cng ngh ha hc ni chung v chuyn ngnh ha cht v bo v thc vt. iu ny cng lm cho chng em thm yu ngh m mnh la chn. Cch lm, quy trnh lm mt n, mt ti nh. N gip cho chng em c kinh nghim, hay y chnh l bc tp duyt cho nhng ti nghin cu sau ny S phi hp, cch lm vic theo nhm. Quy trnh tng hp v cc kim thc v Phenobarbital. iu quan trng nht l chng em nhn ra nhng kin thc trng tm m mnh cn phi trau di trong nhng k tip theo c th hon thnh tt chng trnh hc ca mnh. Cui cng chng em xin cm n c gio Nguyn Thy M gip chng em hon thnh ti. H ni ngy 3 thng 12 nm 2010

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Ti liu tham kho

Ti liu ting Vit: 1.Bch khoa ton th m ting Vit,http://vi.wikipedia.org/ 2. GS.TS. o Vn Phan, Dc l hc tp1,nXBYH. 3. Dc th Vit Nam ,http://duocthu.com/index.php 4.Hi ng dc in, 2002. Dc in Vit Nam III. 5.To Duy Cn, 1998, Tra cu s dng thuc v bit d-c n-c ngoi, nh xut bn khoa hc v k thut, 497.

Ti liu Nc ngoi: 6."Chemical Engineering Overview" Prepared as part of the Sloan Career Cornerstone Center (www.careercornerstone.org) 7.Synthesis of phenobarbital, an an ticonvulsant drug, ca khesorn naniachit, v cng s. google.com 8.Kirk Othmer, 1965, Encyclopedia of chemical technology, 21, 37

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