["Ph\u01b0\u01a1ng \u00e1n hi\u1ec7n nay \u0111\u1ec3 ng\u01b0ng t\u1ee5 Claisen ch\u00e9o l\u00e0 C-axyl h\u00f3a enolat lithi c\u1ee7a este b\u1eb1ng cloanhi\u0111rit axit \u1edf \u0111i\u1ec1u ki\u1ec7n r\u1ea5t \u00eam d\u1ecbu trong THF : RCH2COOC2Hs 1 .(i-C \u1ef1 \u1ec97)2N L i,T H F ,- 780C \u201e + LiCl - - - ---------------- \u00bb R 'C O C H -C \\\" 2.R -C O C 1 1 OC2H5 R (60 - 80% ) Ph\u01b0\u01a1ng ph\u00e1p th\u00f4ng d\u1ee5ng n\u00e0y cho ph\u00e9p nh\u1eadn \u0111\u01b0\u1ee3c este c\u1ee7a P-xetoaxit kh\u00e1c nhau (P-xetoeste). Ph\u01b0\u01a1ng ph\u00e1p hi\u1ec7n \u0111\u1ea1i kh\u00e1c \u0111\u1ec3 cacboxyl h\u00f3a xeton l\u00e0 ng\u01b0ng t\u1ee5 enolat ki\u1ec3m c\u1ee7a xeton v\u1edbi \u0111ietyl cacbonat ho\u1eb7c \u0111ietyl clofomiat ClCOOEt \u0111\u01b0\u1ee3c x\u00fac t\u00e1c b\u1eb1ng NaH ho\u1eb7c LDA : _ OEt _ 3CH C 0 0 H - H 20 \/ ' \u1ef4 0 \u01a0\u00b0 l _ NaH \/ Y\\\" I toluen, 1 10\u00b0c cOOEt \u00b0\u00b0c ^CO OEt OEt \u0110\u1eb7c bi\u1ec7t, khi ng\u01b0ng t\u1ee5 v\u1edbi xeton ta nh\u1eadn \u0111\u01b0\u1ee3c \u1eca3-hi\u0111roxi este : CH3COOEt 1 . [(CH3)3Si]2NLi. THF. - 78\u00b0c \/ \\\\ OH 2 .0 = 0 CH2COOEt (80 - 90%) 14.8 Ph\u1ea3n \u1ee9ng Refom atski (Reformatsky) H\u1ee3p ch\u1ea5t c\u01a1 magie v\u00e0 c\u01a1 lithi kh\u00f4ng th\u1ec3 \u0111i\u1ec1u ch\u1ebf b\u1eb1ng c\u00e1ch cho magie ho\u1eb7c lithi t\u00e1c d\u1ee5ng v\u1edbi este c\u00f3 nh\u00f3m th\u1ebf halogen \u1edf v\u1ecb tr\u00ed a b\u1edfi v\u00ec thu\u1ed1c th\u1eed Grinha v\u00e0 h\u01a1p ch\u1ea5t c\u01a1 lithi t\u01b0\u01a1ng t\u00e1c v\u1edbi este. Vi\u1ec7c \u0111i\u1ec3u ch\u1ebf este c\u1ee7a 3=hi\u0111roxi \u00e2xit do ph\u1ea3n \u1ee9ng c\u1ed9ng h\u1ee3p d\u1eabn xu\u1ea5t c\u01a1 kim c\u1ee7a este v\u00e0o nh\u00f3m cacbonyl c\u1ee7a an\u0111ehit v\u00e0 xeton d\u01b0\u1ee3c th\u1ef1c hi\u1ec7n th\u00e0nh c\u00f4ng khi d\u00f9ng d\u1eabn xu\u1ea5t c\u1ee7a k\u1ebdm. Ph\u1ea3n \u1ee9ng n\u00e0y \u0111\u01b0\u1ee3c nh\u00e0 h\u00f3a h\u1ecdc Nga S.N. Re\u00edomatski ph\u00e1tminhn\u00e3m 1887. a-Bromeste t\u01b0\u01a1ng t\u00e1c v\u1edbi an\u0111ehit ho\u1eb7c xeton v\u00e0 k\u1ebdm kim lo\u1ea1itrongm\u00f4itr\u01b0\u1eddng aprotonic kh\u00f4ng ph\u00e2n c\u1ef1c (benzen, toluen) s\u1ebd t\u1ea1o th\u00e0nh este P-hi\u0111roxiaxit. Trong ph\u1ea3n \u1ee9ng n\u00e0y kh\u00f4ng c\u1ea7n ph\u1ea3i t\u00e1ch h\u1ee3p ch\u1ea5t c\u01a1 k\u1ebdm ra tr\u01b0\u1edbc m\u00e0 ch\u1ec9 c\u1ea7n th\u00eam k\u1ebdm tr\u1ef1c ti\u1ebfp v\u00e0o h\u1ed7n h\u1ee3p h\u1ee3p ch\u1ea5t cacbonyl v\u00e0 a-bromeste trong toluen ho\u1eb7c benzen. Khi tu\u00e2n th\u1ee7 nghi\u00eam ng\u1eb7t \u0111i\u1ec1u ki\u1ec7n th\u1ef1c nghi\u1ec7m, hi\u1ec7u su\u1ea5t este th\u01b0\u1eddng r\u1ea5t cao v\u00e0 \u0111\u1ea1t \u0111\u1ebfn 60 - 90% : OZnBr CH3CHCOOEt + C6H5 - C - C H 3 + Zn -^ -nf n-\u00bb C6H5 - C - C H - C f ------> 1 5 l\u00ed 80C 11 OEt Br 0 CH3 CH3 OH c 6h 5 - c - c h - < \u00b0 o c X , 1 V OEt ch 3c h 3 (80%) 384","\/\\\\ _ _____ 1 . Zn, toluen, 80\u00b0c \/ \\\\ ,OH < y = o + BrCH2COOEt (X \\\\\u2014 \/ 2. H20 - \u00ed-I2S0 4. 0 c \\\\\u2014 \/ CH2COOEt \u201e \u201e \u201e\u201e 1. Zn. toluen, 80\u00b0c _ _ 2 h 20 - h' s o ^ \u01a1\u0129c > CH3(CH2)5C H -C H 2COOEt CH3CCH2)5C - H + BrCH2COOEt OH 0 \u0110\u1ec3 tr\u00e1nh cho este v\u1edbi nh\u00f3m hi\u0111roxyl b\u1eadc hai ho\u1eb7c b\u1eadc ba b\u1ecb lo\u1ea1i n\u01b0\u1edbc th\u00e0nh este a , p-kh\u00f4ng no th\u00ec c\u1ea7n ph\u1ea3i ki\u1ec3m so\u00e1t c\u1ea9n th\u1eadn \u0111i\u1ec1u ki\u1ec7n thu\u1ef7 ph\u00e2n axit ancolat k\u1ebdm v\u00e0 ph\u1ea3i ti\u1ebfn h\u00e0nh \u1edf 0\u00b0c Trong th\u1eddi gian d\u00e0i ng\u01b0\u1eddi ta c\u1ed3ng nh\u1eadn thu\u1ed1c th\u1eed Re\u00edomatski \u0111\u01b0\u1ee3c ch\u1ebf t\u1ea1o t\u1eeb a-bromeste c\u00f3 c\u00f4ng th\u1ee9c BrZnCH(R)COOEt. Hi\u1ec7n nay, c\u1ea5u tr\u00fac c\u00f3 c\u01a1 s\u1edf h\u01a1n \u0111\u00f3 l\u00e0 enolat k\u1ebdm : RCH = c - O ZnB r. V\u00ec v\u1eady ph\u1ea3n \u1ee9ng Refomatski \u0111\u01b0\u01a1c xem nh\u01b0 tr\u01b0\u1eddng h\u1ee3p ri\u00eang c\u1ee7a OEt s\u1ef1 ng\u01b0ng t\u1ee5 an\u0111ol gi\u1eefa h\u1ee3p ch\u1ea5t cacbonyl v\u00e0 este enolat k\u1ebdm. \u0110\u1ed9ng l\u1ef1c c\u1ee7a qu\u00e1 tr\u00ecnh l\u00e0 s\u1ef1 t\u1ea1o th\u00e0nh ph\u1ee9c chelat m\u00e0 cation k\u1ebdm th\u1ef1c hi\u1ec7n vai tr\u00f2 t\u00e1c nh\u00e2n chelat h\u00f3a : \/B r OH \/Z n .. R - C - C H 2COOEt R - C - R ' + CH2= C ^ ------ > R ^ ? V l \u00cc OEt XA R' CH2 OEt R \u00b0 Dung m\u00f4i kh\u00f4ng ph\u00e2n c\u1ef1c x\u00fac ti\u1ebfn cho vi\u1ec7c t\u1ea1o th\u00e0nh ph\u1ee9c chelat v\u00e0 dung m\u00f4i n\u00e0y kh\u00f4ng solvat h\u00f3a hi\u1ec7u qu\u1ea3 cho ion k\u1ebdm. C\u01a1 ch\u1ebf c\u1ee7a ph\u1ea3n \u1ee9ng Refomatski r\u1ea5t ph\u00f9 h\u1ee3p v\u1edbi d\u1eef ki\u1ec7n th\u1ef1c nghi\u1ec7m b\u1edfi v\u00ec p~ v\u00e0 \u1ef4-bromeste kh\u00f4ng c\u00f3 kh\u1ea3 n\u0103ng t\u1ea1o th\u00e0nh enolat k\u1ebdm n\u00ean kh\u00f4ng tham gia ph\u1ea3n \u1ee9ng Re\u00ed\u00f2matski. 14.9 Ng\u01b0ng t\u1ee5 Knoevenagen (Knoevenagel) Ph\u1ea3n \u1ee9ng ng\u01b0ng t\u1ee5 gi\u1eefa an\u0111ehit v\u00e0 xeton th\u01a1m ho\u1eb7c an\u0111ehit v\u00e0 xeton thu\u1ed9c d\u00e3y b\u00e9o v\u1edbi axit malonic v\u00e0 c\u00e1c h\u1ee3p ch\u1ea5t kh\u00e1c c\u00f3 nh\u00f3m metylen linh \u0111\u1ed9ng khi c\u00f3 m\u1eb7t x\u00fac t\u00e1c baz\u01a1 \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 ng\u01b0ng t\u1ee5 Knoevenagen (1896): R \/ C = o + c h 2^ X p--per\u00ed\u0111in-> % = < x + h 20 R\u2019 Y RY v\u1edbi X, Y = COOH, COOR, CN, NO 2 Ph\u1ea3n \u1ee9ng Knoevenagen \u0111\u01b0\u1ee3c d\u00f9ng r\u1ed9ng r\u00e3i trong t\u1ed5ng h\u1ee3p h\u1eefu c\u01a1 nh\u01b0 m\u1ed9t ph\u01b0\u01a1ng ph\u00e1p th\u00f4ng d\u1ee5ng \u0111\u1ec3 \u0111i\u1ec1u ch\u1ebf axit, este, nitrin a, P-kh\u00f4ng no (b\u1ea3ng 14.3). 385","B \u1ea3ng 14.3 T\u1ed5ng h\u1ee3p axit, este v\u00e0 nitrin a, (3-kh\u00f4ng no theo Knoevenagen o c h 3< ch2)5c CX + CH2(COOH)2 - 100 c > pyri\u0111in, \u25a0\u00bb CH3(CH2)5C H = C H -C O O H + c o 2 + h 20 (79%) o piperi\u0111in \/\\\\ CN ^ COOCoH o + N C - C H 2COOC2H5. C H 3COOH \/ 2n 5 benzen, 80\u00b0c \\\\ (100%) o piperi\u0111in f _ \/ - c + CH2(COOH)2 CH = CHCOOH OoN' H 0 2N (80%) + CH2(COOH)2 piperi\u0111in o C H = CHCOOH 100\u00b0c (91%) CH=CHCN piperi\u0111in + N C - C H 2COOH pyri\u0111in, 100\u00b0c o o + CH2(COOC2H5)2 piperi\u0111in, T1CI4 \/ c o o c 2h. benzen c o o c 2h 5 (78%) piperi\u0111in COOC2H3 c o o c 2h 5 CH2(COOC2H5)2 - C-2CiOQH.. > \/ \\\\ - C H = C benzen \\\\= = \/ (90%) piperi\u0111in .C N 0 =o + CH2(CN)2 benzen, 80 c \\\\ __\/ x (75%) S\u1ef1 kh\u00e1c nhau \u0111\u1eb7c bi\u1ec7t gi\u1eefa ng\u01b0ng t\u1ee5 Knoevenagen v\u00e0 ng\u01b0ng t\u1ee5 an\u0111ol l\u00e0 \u1edf ng\u01b0ng t\u1ee5 Knoevenagen d\u00f9ng x\u00fac t\u00e1c amin, pyri\u0111in, piperi\u0111in ho\u1eb7c h\u1ed7n h\u1ee3p c\u1ee7a ch\u00fang. Amin c\u00f3 t\u00ednh baz\u01a1 v\u1eeba \u0111\u1ee7 \u0111\u1ec3 t\u1ea1o n\u1ed3ng \u0111\u1ed9 anion c\u00e2n b\u1eb1ng \u1ed5n \u0111\u1ecbnh khi \u0111eproton h\u00f3a este malonic, este xianaxetic, este nitroaxetic v\u00e0 este axetoaxetic c\u00f3 pKa ~ 10. Tuy nhi\u00ean, amin kh\u00f4ng c\u00f3 kh\u1ea3 n\u0103ng chuy\u1ec3n an\u0111ehit v\u00e0 xeton c\u00f3 pKa 1 8 - 2 0 th\u00e0nh ion enolat li\u00ean h\u1ee3p. \u0110i\u1ec1u quan tr\u1ecdng l\u00e0 386","gi\u1ea3m thi\u1ec3u \u0111\u01b0\u1ee3c s\u1ef1 t\u1ef1 ng\u01b0ng t\u1ee5 c\u1ee7a h\u1ee3p ch\u1ea5t cacbonyl. An\u0111ehit tham gia ph\u1ea3n \u1ee9ng Knoevenagen v\u1edbi c\u00e1c h\u1ee3p ch\u1ea5t kh\u00e1c nhau c\u00f3 nh\u00f3m metylen linh \u0111\u1ed9ng. Xeton \u00edt ho\u1ea1t \u0111\u1ed9ng h\u01a1n v\u00e0 d\u1ec5 d\u00e0ng ph\u1ea3n \u1ee9ng v\u1edbi CH2(CN)2 v\u00e0 CNCH2COOEt, nh\u01b0ng \u0111\u1ec3 ph\u1ea3n \u1ee9ng v\u1edbi este malonic v\u00e0 este axetoaxetic th\u00ec c\u1ea7n ph\u1ea3i c\u00f3 x\u00fac t\u00e1c TiCl4. \u0110i\u1ec1u ki\u1ec7n t\u1ed1i \u01b0u c\u1ee7a ng\u01b0ng t\u1ee5 Knoevenagen l\u00e0 d\u00f9ng x\u00fac t\u00e1c axetat piperi\u0111in c\u00f9ng v\u1edbi baz\u01a1 t\u1ef1 do. C\u01a1 ch\u1ebf ch\u00ednh x\u00e1c c\u1ee7a ph\u1ea3n \u1ee9ng n\u00e0y c\u0169ng ch\u01b0a th\u1eadt r\u00f5 r\u00e0ng, nh\u01b0ng c\u00f3 th\u1ec3 c\u00f3 gi\u1ea3 thi\u1ebft r\u1eb1ng, trong m\u00f4i tr\u01b0\u1eddng \u0111\u1ec7m (axetat piperi\u0111in), ph\u1ea7n t\u1eed c\u00f3 kh\u1ea3 n\u0103ng ph\u1ea3n \u1ee9ng l\u00e0 mu\u1ed1i imini, \u0111\u01b0\u1ee3c t\u1ea1o th\u00e0nh t\u1eeb h\u1ee3p ch\u1ea5t cacbonyl v\u00e0 amin b\u1eadc hai khi c\u00f3 m\u1eb7t axit li\u00ean h\u1ee3p. Sau \u0111\u00f3 mu\u1ed1i imini ph\u1ea3n \u1ee9ng v\u1edbi ion enolat, cu\u1ed1i c\u00f9ng t\u00e1ch lo\u1ea1i pyrimi\u0111in \u0111\u1ec3 ho\u00e0n ch\u1ec9nh s\u1ef1 t\u1ea1o th\u00e0nh h\u1ee3p ch\u1ea5t a, P-kh\u00f4ng no : \/\u2014 \\\\ AcOH \/ \u2014 \\\\+ R -C -H + HN > <=r> ( N = CHR.OAc + H20 o \/ \u2014\\\\ -_ \/ . XA \/ \\\\+ + HNO c< \\\" + { _ nh2 \/X CH\/ \/-A + -) - _ rL x ( N \u2014CHR + c h ' < = \u00b1 R C H -C H \\\" <-------- \u00bb R - C H - C \\\" V -y Y I Y +T i Y NH o R\\\\ \/ x \/-\\\\ \/~ N + c= c + HN > + ( NH2 HY X v\u00e0 Y = COOEt; CN M\u1ed9t ph\u01b0\u01a1ng ph\u00e1p kh\u00e1c \u0111\u1ec3 t\u1ed5ng h\u1ee3p axit a , P-kh\u00f4ng no \u0111\u00e3 \u0111\u01b0\u1ee3c Peckin ph\u00e1t tri\u1ec3n n\u0103m 1868. Trong ph\u1ea3n \u1ee9ng Peckin, an\u0111ehit th\u01a1m ho\u1eb7c th\u01a1m b\u00e9o ng\u01b0ng t\u1ee5 trong \u0111i\u1ec1u ki\u1ec7n kh\u1eafc nghi\u1ec7t h\u01a1n \u1edf 170 - 200\u00b0c v\u1edbi anhi\u0111rit axit b\u00e9o khi c\u00f3 m\u1eb7t mu\u1ed1i c\u1ee7a axit cacboxylic \u1ec9\u00e0m t\u00e1c nh\u00e2n baz\u01a1 : RCH?COONa _ \/ COOH 1 2ArCHO + v(RCH2C 0)20 1\u201470 - 200-c-- > A rC H = c \\\" + RCH2zCOOH Th\u00ed d\u1ee5 \u0111\u01a1n gi\u1ea3n nh\u1ea5t l\u00e0 ph\u1ea3n \u1ee9ng \u0111i\u1ec1u ch\u1ebf axit xinamic khi cho benzan\u0111ehit t\u00e1c d\u1ee5ng v\u1edbi anhi\u0111rit axetic c\u00f3 m\u1eb7t kali axetat l\u00e0m x\u00fac t\u00e1c : C06H35CHO + (CH3C 0 )20 (CCHH33CCQ0Q)2-0 ,-188g0i5\u1edd C6H5CH=CH CO O H J1 (60%) Ph\u1ea3n \u1ee9ng Peckin l\u00e0 m\u1ed9t d\u1ea1ng ph\u00e1t tri\u1ec3n c\u1ee7a ng\u01b0ng t\u1ee5 an\u0111ol trong \u0111\u00f3 vai tr\u00f2 t\u00e1c nh\u00e2n nucleophin l\u00e0 ion enolat c\u1ee7a anhi\u0111rit axit. C\u01a1 ch\u1ebf ph\u1ea3n \u1ee9ng c\u00f3 th\u1ec3 nh\u01b0 sau : 387","(CH3C 0)20 CII3COO oo - \u25a0\u25a0\u00bb II 1: \u00a9 t\u00b0 CH3- C - 0 - C - C H 2 00 \u1ecd\u1ecd II II - \u0129 II ArCHO + CH3- C - 0 - C - C H 2 < = \u1ec9 CH3- C - 0 - C n J \/C H , o - HC ^ I Ar \u1ecc _ \u00ecf \u00a3 O -C -C H 3(CH C 0)20 HO o i\u201e i ------\u25baA r - C H - C H 2- C r _ ----- > A r - C H - C H - C - 0 - C - C H 3 ------ > 1 \u1ece-COCH 3 0\u201c f\u0129 ^ \u00f3 -c -c h 3 I 0 ------ \u00bb ArCH= CHCOOAc + CH3COOH + CH3COCT ----- > ------\u00bb ArCH= CH\u2014COOH + Ac20 + AcO~ Hi\u1ec7u su\u1ea5t c\u1ee7a axit xinamic v\u00e0 d\u1eabn xu\u1ea5t ph\u1ee5 thu\u1ed9c v\u00e0o b\u1ea3n ch\u1ea5t nh\u00f3m th\u1ebf trong v\u00f2ng benzen c\u1ee7a an\u0111ehit th\u01a1m. Nh\u00f3m th\u1ebf h\u00fat electron (N 02, CN, Cl, Br...) c\u00f3 kh\u1ea3 n\u0103ng l\u00e0m t\u00e3ng hi\u1ec7u su\u1ea5t axit a, P-kh\u00f4ng no, trong khi \u0111\u00f3 nh\u00f3m \u0111\u1ea9y electron (CH3, C2H5, N(CH3)3) l\u00e0m gi\u1ea3m \u0111\u00e1ng k\u1ec3 hi\u1ec7u su\u1ea5t c\u1ee7a axit. Ng\u01b0\u1eddi ta kh\u00f4ng d\u00f9ng ph\u1ea3n \u1ee9ng Peckin cho c\u00e1c an\u0111ehit d\u00e3y b\u00e9o v\u00ec an\u0111ehit c\u00f3 khuynh h\u01b0\u1edbng t\u1ef1 ng\u01b0ng t\u1ee5. \u0110\u1ec3 di\u1ec1u ch\u1ebf cumarin ng\u01b0\u1eddi ta \u0111i t\u1eeb \u01a1-hi\u0111roxibenzan\u0111ehit theo ph\u01b0\u01a1ng tr\u00ecnh ph\u1ea3n \u1ee9ng sau : CHCOOH ^ CH 0 ________ _ CHiCOONa 0 -C -C H 3 0\u0129 14.10 Ph\u1ea3n \u1ee9ng Mannich C\u00e1c xeton c\u00f3 Ha t\u00e1c d\u1ee5ng v\u1edbi foman\u0111ehit v\u00e0 hi\u0111ro clorua c\u1ee7a amin b\u1eadc hai t\u1ea1o th\u00e0nh P-aminoxeton, \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 baz\u01a1 Mannich, c\u00f2n ph\u1ea3n \u1ee9ng aminoankyl h\u00f3a d\u01b0\u1ee3c g\u1ecdi l\u00e0 ph\u1ea3n \u1ee9ng Mannich (1912). Kh\u1ea3 n\u0103ng t\u1ed5ng h\u1ee3p n\u00e0y \u0111\u01b0\u1ee3c h\u1ea1n ch\u1ebf b\u1eb1ng c\u00e1ch s\u1eed d\u1ee5ng amin b\u1eadc hai, b\u1edfi v\u00ec c\u00e1c s\u1ea3n ph\u1ea9m \u0111\u01b0\u1ee3c t\u1ea1o th\u00e0nh khi ng\u01b0ng t\u1ee5 v\u1edbi amin b\u1eadc m\u1ed9t s\u1ebd tham gia v\u00e0o m\u1ed9t lo\u1ea1t ph\u1ea3n \u1ee9ng chuy\u1ec3n h\u00f3a ti\u1ebfp theo. Hi\u1ec7u su\u1ea5t ph\u1ea3n \u1ee9ng t\u1ea1o th\u00e0nh baz\u01a1 Mannich kh\u00e1 cao, th\u00ed du : 388","o o+ + HCHO + Me2NH \u2014 CH2-N H M e 2Cl L C2H5OH (85%) P h c f + HCHO + Me2NH P h - C - C H 2CH2-N H M e 2Cl c H i c2h5\u00b0h \u00ecr o 0 o (70%) + HCHO + n N H Ti\u1ec3u ph\u00e2n electrophin ho\u1ea1t \u0111\u1ed9ng trong ph\u1ea3n \u1ee9na Mannich l\u00e0 mu\u1ed1i imini \u0111\u01b0\u1ee3c sinh ra t\u1eeb foman\u0111ehit v\u00e0 amin b\u1eadc hai v\u1edbi x\u00fac t\u00e1c axit : HCHO + R2NH <=\u00b1 HOCH2NR2 Hemiaminal H + + HOCH2NR2 <= > H2O ^ C H 2 ^ N R 2 <==* CH2 = N R 2 + H20 Cation imini Mu\u1ed1i imini c\u0169ng c\u00f3 th\u1ec3 nh\u1eadn \u0111\u01b0\u1ee3c t\u1eeb ph\u1ea3n \u1ee9ng c\u1ee7a foman\u0111ehit v\u1edbi \u0111imetylamin trong metylen clorua c\u00f3 m\u1eb7t HBF4 \u1edf nhi\u1ec7t \u0111\u1ed9 th\u1ea5p : CH2C12. h b f 4 + HCHO + Me2NH ----- -> CH2= N M e2BF4 - 20 c Ti\u1ebfp theo, mu\u1ed1i imini t\u01b0\u01a1ng t\u00e1c v\u1edbi d\u1ea1ng enol c\u1ee7a xeton : \u1ec6\u1eca\u00ed\u1ead R - C - C H 2R' ? = \u00bb r - c = Q : h r ' \u2014 - - Me2> R - C - C H ^ R \u1ec9\u00ed (H \u00ec CH2N M e2 o l:OH 02 S\u1ef1 t\u1ea5n c\u00f4ng electrophin c\u1ee7a cation imini \u01b0u ti\u00ean h\u01b0\u1edbng v\u00e0o nguy\u00ean t\u1eed cacbon b\u1ecb th\u1ebf nhi\u1ec1u nh\u1ea5t c\u1ee7a enol. S\u1ef1 c\u1ea3i bi\u00ean m\u1edbi nh\u1ea5t c\u1ee7a ph\u1ea3n \u1ee9ng Mannich l\u00e0 d\u1ef1a v\u00e0o vi\u1ec7c s\u1eed d\u1ee5ng ete boric v\u00e0 ete silylic c\u1ee7a enol. Vinyloxiboran \u0111\u01b0\u1ee3c \u0111i\u1ec1u ch\u1ebf b\u1eb1ng c\u00e1ch cho xeton t\u00e1c d\u1ee5ng v\u1edbi diankylboryltriflometansunfonat c\u00f3 m\u1eb7t amin b\u1eadc ba : (C4H9)3B + CF3S 0 3H ------ \u00bb (C4H9)2B 0 S 0 2CF3 \u2014 Et2CQ------> N(\/-C3H7)2Et (84%) \u25a0\u00bb CH3CH2 - C = C H C H 3 + CF3S 0 3 NH(z-C3H7)2Et OB(C4H9)2 (95%) 389","CH3CH2- C = CHCH3 + CH2 = N M e2CF3COO \u0110MSQ> OB(C4H9)2 \u1ec9CH2 T 0 \u1ec9CH! 2:N\u201cMe32 + C F 3 C 0 0 T O Ete silylic c\u1ee7a enol c\u0169ng ph\u1ea3n \u1ee9ng t\u01b0\u01a1ng t\u1ef1 : OSiMe3 + o 3 l)CH2 = NR2X , c h 2n r 2 t\u00ecci4, CH2C12 + Me3SiX 2) H20 Ng\u00e0y nay, \u0111\u1ec3 ng\u01b0ng t\u1ee5 axeton v\u00e0 d\u1eabn xu\u1ea5t c\u1ee7a ch\u00fang ng\u01b0\u1eddi ta s\u1eed d\u1ee5ng mu\u1ed1i imini c\u00f3 s\u1eb5n l\u00e0 CH2 = N R 2X~. 14.11 Ng\u01b0ng t\u1ee5 benzoin Ng\u01b0ng t\u1ee5 benzoin thu\u1ed9c v\u00e0o lo\u1ea1i ph\u1ea3n \u1ee9ng l\u00e2u \u0111\u1eddi nh\u1ea5t trong h\u00f3a h\u1eefu c\u01a1, n\u00f3 \u0111\u01b0\u1ee3c Libic v\u00e0 Vu\u00eal\u01a1 t\u00ecnh c\u1edd ph\u00e1t hi\u1ec7n n\u0103m 1832 khi x\u1eed l\u00fd benzan\u0111ehit v\u1edbi kali xianua. H\u1ee3p ch\u1ea5t a-hi\u0111roxixeton t\u1ea1o th\u00e0nh trong ph\u1ea3n \u1ee9ng n\u00e0y \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 benzoin, t\u1eeb \u0111\u00f3 c\u00f3 t\u00ean g\u1ecdi ph\u1ea3n \u1ee9ng ng\u01b0ng t\u1ee5 benzoin : \u1eccH KCN, EtOH _ I PhCHO + PhCHO <\u25a0- = = r > P h - C H - C - P h 0 (90%) Trong ng\u01b0ng t\u1ee5 benzoin c\u00f3 s\u1ef1 tham gia c\u1ee7a hai ph\u00e2n t\u1eed an\u0111ehit th\u01a1m ho\u1eb7c an\u0111ehit d\u1ecb v\u00f2ng c\u00f3 m\u1eb7t ion xianua l\u00e0m x\u00fac t\u00e1c. Ph\u1ea3n \u1ee9ng l\u00e0 thu\u1eadn ngh\u1ecbch v\u00e0 khi x\u1eed l\u00fd benzoin v\u1edbi h\u1ed7n h\u1ee3p kali xianua v\u00e0 an\u0111ehit th\u01a1m kh\u00e1c s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c benzoin h\u1ed7n t\u1ea1p : ArCHOHCOAr' + Ar\\\"CHO KCN\u2019E\u2018QH > ArCHOHCOAr\\\" + Ar'CHO h 20 N\u00f3i chung t\u1eeb h\u1ed7n h\u1ee3p \u0111\u1eb3ng mol c\u1ee7a hai an\u0111ehit kh\u00e1c nhau, v\u1ec1 m\u1eb7t l\u00fd thuy\u1ebft l\u00e0 ph\u1ea3i nh\u1eadn \u0111\u01b0\u1ee3c 4 benzoin, tuy nhi\u00ean trong m\u1ed9t s\u1ed1 tr\u01b0\u1eddng h\u1ee3p ch\u1ec9 nh\u1eadn \u0111\u01b0\u1ee3c m\u1ed9t benzoin h\u1ed7n t\u1ea1p. Nhi\u1ec1u an\u0111ehit th\u01a1m ch\u1ee9a nh\u00f3m th\u1ebf \u0111\u1ea9y electron nh\u01b0 \u0111imetylaminobenzan\u0111ehit, piperonan\u0111ehit, 2,4-\u0111imetoxibenzan\u0111ehit... kh\u00f4ng tham gia ng\u01b0ng t\u1ee5 benzoin. Tuy nhi\u00ean, ch\u00fang tham gia v\u00e0o ng\u01b0ng t\u1ee5 h\u1ed7n t\u1ea1p v\u1edbi an\u0111ehit kh\u00e1c, ph\u1ea3n \u1ee9ng n\u00e0y \u0111\u01b0\u1ee3c d\u00f9ng c\u00f3 hi\u1ec7u qu\u1ea3 trong th\u1ef1c h\u00e0nh t\u1ed5ng h\u1ee3p, th\u00ed d\u1ee5 : PhCHO + ^ N\u2014\/ \\\\ - C H O - KC~ \u2014 tQ- -> PhCHOH\u2014C \u2014\/ ch3 \u1ecb \\\\==\/ h 3c w 0 (86%) 390","C\u01a1 ch\u1ebf ph\u1ea3n \u1ee9ng d\u1ef1a tr\u00ean c\u00e1c d\u1eef ki\u1ec7n \u0111\u1ed9ng h\u1ecdc c\u00f3 th\u1ec3 nh\u01b0 sau : \/ C = N h 20 \/C \u2014N _ (1) A rC ^ + :CN <==> ArCH\\\" <=\u00bb ArCH^ + OH H 0\u2022\u2022 : OH \/C = N OH~ - \/ C\u2014N (2) A rC H ^ < = \u00b1 ArC\\\" + H20 OH OH 8- CN H CN H - \/ C\u201c N 5+^0 1I H20 1I A r - C - c - Ar + OH (3) A r c \\\" + ArC^ < = \u00b1 Ar ~ c - c - Ar < = > 11 OH H 1 1_ OH OH OH o CN H r CN H H Ii OH' \u1ecaL 1 (4) A r - C - C - A r < = \u00b1 A r - C - C - A r < = \u1ec9 A r - C - C - A r + CN I I r1 1 \u01291 OH OH ^ o OH o OH C\u01a1 ch\u1ebf n\u00e0y gi\u1ea3i th\u00edcht\u1ea1i sao d\u00f9ng ionxian l\u00e0m x\u00fac t\u00e1c. Ch\u1ea5t x\u00fac t\u00e1ctrongng\u01b0ng t\u1ee5 benzoin kh\u00f4ng ch\u1ec9 l\u00e0 ch\u1ea5tnucleophin t\u1ed1t \u0111\u1ed1i v\u1edbi nh\u00f3m cacbonyl m\u00e0 c\u00f2nl\u00e0m x\u00fact\u00e1c cho s\u1ef1 d\u1ecbch chuy\u1ec3n proton t\u1eeb cacbon \u0111\u1ebfn oxi \u0111\u1ec3 t\u1ea1o th\u00e0nh cacbanion benzylic b\u1ec1n, trong \u0111\u00f3 nh\u00f3m xian h\u00fat electron tham gia v\u00e0o s\u1ef1 gi\u1ea3i t\u1ecfa \u0111i\u1ec7n t\u00edch. S\u1ea3n ph\u1ea9m ng\u01b0ng t\u1ee5 a-hi\u0111roxixeton d\u1ec5 d\u00e0ng b\u1ecb oxi h\u00f3a b\u1eb1ng oxit bismut (III) ho\u1eb7c \u0111\u1ed3ng (II) axetat th\u00e0nh 1,2-\u0111ixeton v\u1edbi hi\u1ec7u su\u1ea5t cao : R -C -C H O H R ' + Cu(OAc)2 ------> R - C - C - R ' l\u0129 l\u0129 II oo 0 (75 - 95%) lon xian ch\u1ec9 x\u00fac t\u00e1c cho s\u1ef1 ng\u01b0ng t\u1ee5 an\u0111ehit th\u01a1m. V\u1edbi an\u0111ehit d\u00e3y b\u00e9o th\u00ec ph\u1ea3i d\u00f9ng mu\u1ed1i thiazoli l\u00e0m ch\u1ea5t x\u00fac t\u00e1c, c\u1ee5 th\u1ec3 l\u00e0 d\u00f9ng N-\u0111o\u0111exylthiazoli bromua, trong \u0111\u00f3 c\u00f3 m\u1ea1ch ankyl d\u00e0i l\u00e0m cho n\u00f3 d\u1ec5 tan v\u00e0o dung m\u00f4i h\u1eefu c\u01a1 th\u00f4ng th\u01b0\u1eddng : r - N - C ,2H25 \u1ecd \u1eccH Br\\\" \u0129 1 ____________ \u25a0 2 CH3CH2CH2CHO \u2014> CH3CH2CH2C - C H C H 2LCH12CH35 3 21 benzen, NEt, i 22 (76%) Khi c\u1ed9ng h\u1ee3p ion xian v\u00e0o an\u0111ehit th\u01a1m t\u1ea1o th\u00e0nh cacbanion benzoin trung gian Ar - c \u2014CN . Cacbanion n\u00e0y c\u00f3 kh\u1ea3 n\u0103ng ph\u1ea3n \u1ee9ng cao kh\u00f4ng nh\u1eefng \u0111\u1ed1i v\u1edbi nh\u00f3m OH cacbonyl c\u1ee7a an\u0111ehit, m\u00e0 c\u0169ng ho\u1ea1t \u0111\u1ed9ng \u0111\u1ed1i v\u1edbi nh\u1eefng ch\u1ea5t nh\u1eadn electrophin kh\u00e1c, th\u00ed d\u1ee5 c\u1ed9ng h\u1ee3p v\u00e0o xeton (X, P-kh\u00f4ng no, este, nitrin : 391","ArCHO + CH2= C H - X KCN ho\u1eb7c N(C4H9)4CN Ar \u2014c \u2014CH2CH2X \u00ec > \u0110MF ho\u1eb7c \u0110MSO 0 (60 - 90%) x = \u2014C \u2014R ; - C - O R ; \u25a0CN 0\u00ec 0\u00ec 14.12 Ng\u01b0ng t\u1ee5 \u0110 ichm an (Dieckmann) - S\u1ef1 \u0111\u00f3ng v\u00f2ng Claisen Ng\u01b0ng t\u1ee5 Claisen n\u1ed9i ph\u00e2n t\u1eed \u0111ieste s\u1ebd h\u00ecnh th\u00e0nh v\u00f2ng. S\u1ef1 \u0111\u00f3ng v\u00f2ng Claisen n\u1ed9i ph\u00e2n t\u1eed \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 ng\u01b0ng t\u1ef1 \u0110ichman ho\u1eb7c v\u00f2ng h\u00f3a \u0110ichman. O o o \u1eca T ^ CH2\/ OEt NaH ( 1 \u0111l) \/^C H \u1edd u OEt OEt o C -O E t C -O E t Etyl 2-oxoxiclopentan cacboxylat \u0129 (71 - 81%) o o \u0110ietyl a\u0111ipat ( 1 ,6 -\u0111ieste) T\u1eeb \u0111imetyl pimelat (1,7-\u0111ieste) s\u1ebd thu \u0111\u01b0\u1ee3c metyl 2-oxoxiclohexan cacboxylat: O o o \u0129 s CH2 OMe NaH (l\u0111l) CH OMe C- C-OM e C -O M e 0 OMe \u00ec o 0 \u0110\u00e2y l\u00e0 ph\u01b0\u01a1ng ph\u00e1p \u0111\u01a1n gi\u1ea3n \u0111\u1ec3 t\u1ed5ng h\u1ee3p xeton v\u00f2ng : COOEt c=0 c=0 (CH2)n NaH H20 - H2SOz CH \\\\ COOEt toluen (C H 2)n CHCOOEt Ph\u1ea3n \u1ee9ng x\u1ea3y ra v\u1edbi hi\u1ec7u su\u1ea5t t\u1ed1t (70 - 80%) khi t\u1ea1o th\u00e0nh v\u00f2ng 5 ho\u1eb7c v\u00f2ng 6 ngh\u0129a l\u00e0 khi n = 4 - 5. Tuy v\u1eady, c\u0169ng c\u00f3 th\u1ec3 t\u1ea1o v\u00f2ng l\u1edbn v\u1edbi n > 12 khi d\u00f9ng k\u1ef9 thu\u1eadt pha lo\u00e3ng cao v\u00e0 d\u00f9ng NaH l\u00e0m baz\u01a1. S\u1ef1 \u0111\u00f3ng v\u00f2ng 1 ,3 -xetoeste c\u00f3 14 - 16 cacbon b\u1eb1ng ng\u01b0ng t\u1ee5 \u0110ichman ch\u1ec9 \u0111\u1ea1t \u0111\u01b0\u1ee3c hi\u1ec7u su\u1ea5t 30%. 14.13 T\u1ed5ng h\u1ee3p t\u1eeb este malonic v\u00e0 este axetoaxetic Vi\u1ec7c t\u1ea1o th\u00e0nh ion enolat c\u1ee7a c\u00e1c h\u1ee3p ch\u1ea5t 1 ,3 -\u0111 ica cb o n y l (este malonic, este axetoaxetic v\u00e0 1 ,3 -xetoeste kh\u00e1c) \u0111\u01b0\u1ee3c x\u1ea3y ra d\u1ec5 d\u00e0ng nh\u1edd c\u00f3 hai nh\u00f3m th\u1ebf h\u00fat electron l\u00e0 nh\u00f3m cacbonyl v\u00e0 nh\u00f3m cacbankoxi. Ion enolat c\u1ee7a este malonic v\u00e0 este axetoaxetic c\u00f3 392","t\u00ednh b\u1ec1n l\u1ed5n h\u01a1n ion enolat c\u1ee7a xeton v\u00e0 monoeste l\u00e0 do c\u00f3 s\u1ef1 gi\u1ea3i t\u1ecfa \u0111i\u1ec7n t\u00edch h\u1eefu hi\u1ec7u h\u01a1n nh\u1edd hai nh\u00f3m h\u00fat electron. \u0110i\u1ec1u n\u00e0y \u0111\u01b0\u1ee3c ph\u1ea3n \u1ea3nh l\u00ean gi\u00e1 tr\u1ecb pKa th\u1ea5p c\u1ee7a c\u00e1c h\u1ee3p ch\u1ea5t \u1ea5y. C\u00e1c enolat ki\u1ec1m c\u1ee7a este malonic ch\u1ecbu C-ankyl h\u00f3a \u0111\u1eb7c th\u00f9 v\u00f9ng d\u01b0\u1edbi t\u00e1c d\u1ee5ng c\u1ee7a ankyl halogenua b\u1eadc m\u1ed9t, b\u1eadc hai v\u00e0 sunfonat. V\u1edbi ankyl halogenua b\u1eadc ba ph\u1ea3n \u1ee9ng kh\u00f4ng thu\u1eadn l\u1ee3i v\u00ec trong tr\u01b0\u1eddng h\u1ee3p n\u00e0y h\u01b0\u1edbng ph\u1ea3n \u1ee9ng duy nh\u1ea5t l\u00e0 t\u00e1ch lo\u1ea1i. \u0110\u1ec3 \u00edt t\u1ea1o s\u1ea3n ph\u1ea9m C,C-\u0111iankyi ng\u01b0\u1eddi ta d\u00f9ng ankyl tosylat v\u00e0 c\u00e1c ankyl sunfonat kh\u00e1c thay cho ankyl bromua v\u00e0 ankyl io\u0111ua. Khi \u0111un d\u1eabn xu\u1ea5t c\u1ee7a este malonat v\u1edbi axit clohi\u0111ric \u0111\u1eb7c \u1edf 110 - 120\u00b0c \u0111\u1ec3 thu\u1ef7 ph\u00e2n \u0111\u1ed3ng th\u1eddi \u0111ecacboxyl h\u00f3a s\u1ebd thu \u0111\u01b0\u1ee3c axit axetic th\u1ebf. E t O - C - C H 2- C - O E t + EtO * EtOH + E t O - C - C H - C - O E t \u0129 II II \u0129 00 00 \u0110ietyl malonat lon enolat pKa= 12,9 \/\\\"X FfOH -> CH3 -C H -C H (C O O E t)2 (EtOOC)2CH + CH3- C H - B r + Br I c h 2- c h 3 c h 2- c h 3 (83%) CH3 -C H -C H (C O O E t)2 H1C115^\u201eC> CH3- C H - C H 2COOH + c o 2 CH2- C H 3 c h 2- c h 3 ho\u1eb7c : CH2(COOEt)2 - Et0Na\u2019EtQ- > (CH3)2C H -C (C O O E t)2 (CH3)2CHCHCOOH C2H5 3) (CH3)7cHI C2H5 (35%) Khi d\u00f9ng 1 mol ankyl \u0111ihalogenua \u0111\u1ec3 ankyl h\u00f3a este malonic ng\u01b0\u1eddi ta c\u00f3 th\u1ec3 \u0111i\u1ec1u ch\u1ebf \u0111\u01b0\u1ee3c axit v\u00f2ng, c\u1ee5 th\u1ec3 l\u00e0 axit xiclobutancacboxylic v\u00e0 axit xiclopropancacboxylic : CH2(COOEt)2 ! ; E^ Na\u2019EtQH> COOEt COOH \\\"'COOEt 2V 2) Br(CH2)3Br - K0H\u2019HlO\u1ec8\u1ec8 ~-ll2--> 2) H30 +, t\u00b0 (42 - 44%) Ph\u01b0\u01a1ng ph\u00e1p n\u00e0y c\u0169ng d\u00f9ng \u0111\u1ec3 \u0111i\u1ec1u ch\u1ebf \u0111iaxit n\u1ebfu ch\u00fang ta ankyl h\u00f3a b\u1eb1ng este c\u1ee7a axit co-halogencacboxylic : CH2(COOEt)2 1)EtQNa, Et0- \u00bb CH(COOEt)2 HG1\u1ecb\u1eadC> CH2COOH + C 0 2 + EtOH 2 1 2) Br(CH2)nCOOEt 1 z 115\u00b0c 1 z \u00ed (CH2)nCOOEt (CH2)nCOOH 393","C\u0169ng c\u00f3 th\u1ec3 \u0111i\u1ec1u ch\u1ebf \u0111iaxit b\u1eb1ng ph\u01b0\u01a1ng ph\u00e1p kh\u00e1c l\u00e0 cho ng\u01b0ng t\u1ee5 2 mol natri malonat v\u1edbi 1 ph\u00e2n t\u1eed \u0111ihalogenankan. Th\u00ed d\u1ee5, t\u1eeb metylen bromua v\u00e0 natri malonat s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c axit glutaric, t\u1eeb 1,2-\u0111ibrometan s\u1ebd \u0111\u01b0\u1ee3c axit a\u0111ipic, t\u1eeb 1,3-\u0111ibrompropan s\u1ebd \u0111\u01b0\u1ee3c axit pimelic. Ph\u01b0\u01a1ng ph\u00e1p n\u00e0y ch\u1ec9 \u00e1p d\u1ee5ng cho \u0111\u1ebfn a,(D-\u0111ihalogenankan : CH2Br2 + 2NaCH(COOEt)2 \u2014 N-> (EtOOC)2CHCH2CH(COOEt)2 HC1 f c> EtOH 115 c ------> HOOCCH2CH2CH2COOH Khi ankyl h\u00f3a este axetoaxetic th\u00ec s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c d\u1eabn xu\u1ea5t c\u1ee7a xeton : CH3- C - C H 2COOEt U-^ > CH3\u2014 c \u2014 CH\u2014 COOEt CH3- C - C H 2R + C 0 2 l\u00ed 2) RX 3 |f I t\u00b0 \u00ecr 0 0R 0 Th\u00ed d\u1ee5, \u0111\u1ec3 \u0111i\u1ec1u ch\u1ebf heptan-2-on ng\u01b0\u1eddi ta d\u00f9ng \u00ab-butyl bromua \u0111\u1ec3 ankyl h\u00f3a etyl axetoaxetat: 1CH3JCOCH12COOEt \u2014 e- QK\u2019ete> CH33COCHCOOEt \u2014 NaQf \u20192H0(\u00b0^c- > 2) rt-C4H9Br 2) H30 +, C4H9 ------\u00bb CH3COCH2CH2CH2CH2CH3 Este axetoaxetic d\u1ec5 t\u1ea1o th\u00e0nh \u0111ianion n\u1ebfu cho t\u00e1c d\u1ee5ng v\u1edbi baz\u01a1 m\u1ea1nh nh\u01b0 bis-(trimetylsilyl)ami\u0111ua lithi ho\u1eb7c natri, \u0111iisopropylami\u0111ua lithi, natri hi\u0111rua. Khi cho 1 \u0111\u01b0\u01a1ng l\u01b0\u1ee3ng RX ph\u1ea3n \u1ee9ng v\u1edbi \u0111ianion n\u00e0y th\u00ec n\u00f3 s\u1ebd ankyl h\u00f3a v\u00e0o nguy\u00ean t\u1eed cacbon n\u00e0o c\u00f3 t\u00ednh baz\u01a1 l\u1edbn h\u01a1n v\u00e0 t\u00ednh nucleophin l\u1ed1m h\u01a1n, ngh\u0129a l\u00e0 n\u00f3 s\u1ebd v\u00e0o nguy\u00ean t\u1eed Yso v\u1edbi este : \u00a9 . Li x 0\u1ecc 1 1 RXT H F 0 ? 0 \u00b0r > ^\u00a9 _\u00a9 \/^ c K - y\u00a9 '.\/.- X \\\\. ___ CH3 - C - C H 2COOEt > 0 LiCH2 c h OEt \u0110ianion \u00a9 .. Li o\\\" 'o ------> C-. \u00a9 ,-C h 20 RCH2COCH2COOEt RCH2 CH OEt Th\u00ed d\u1ee5, t\u1eeb etyl axetoaxetat v\u00e0 etyl bromua ng\u01b0\u1eddi ta \u0111\u00e3 nh\u1eadn \u0111\u01b0\u1ee3c etyl 3-oxohexanoat: CH3COCH2COOEt -i)NaH> CH3CH2CH2 - C - C H 2COOEt 2) EtBr II 0 (84%) 394","L\u00fd th\u00fa h\u01a1n n\u1eefa l\u00e0 ng\u01b0\u1eddi ta s\u1eed d\u1ee5ng \u0111ianion \u0111\u1ec3 \u0111iankyl h\u00f3a b\u1eb1ng c\u00e1c t\u00e1c nh\u00e2n ankyl h\u00f3a kh\u00e1c nhau v\u00e0 nh\u1eadn \u0111\u01b0\u1ee3c xeton kh\u00f4ng \u0111\u1ed1i x\u1ee9ng : \u00a9 \u00a9 \u0168 \u0168 o o oo li !l RBr 1: il R\u2019Br \u00a9 -> -C \\\\ yj_jp \u00a9\u00a9 \/ c * 0 .^C THF c h OEt RCH2 CH OEt LiCH2 HO 1* RCH2 \u2014c \u2014CH\u2014COOEt -77^ > RCH2 - C - C H 2R' IT H2 \u00b0 0 R' 0 Ankyl h\u00f3a \u0111ianion c\u1ee7a este axetoaxetic b\u1eb1ng \u0111ihalogenua s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c 1,3-xetoeste v\u00f2ng : \u00a9 Li oo PCTHI3rCnOCn Hi 2rCnOnOnEit -----2-L\u2014iN\u00b1(C-3-H--7---i>)2 e \/ cp^ . \u00a9 t Br(CH2)3Br CH2 ch OEt ch2- ch2 h 2c c = 0 \\\\ \u00ab r\u00a9 \/ CH2 CH -CO O Et c Br 11.14 Ng\u01b0ng t\u1ee5 ion g\u1ed1c c\u1ee7a xeton v\u00e0 este D\u01b0\u1edbi t\u00e1c d\u1ee5ng c\u1ee7a ch\u1ea5t kh\u1eed m\u1ea1nh c\u00f3 m\u1ed9t electron nh\u01b0 kim lo\u1ea1i ki\u1ec1m, trong m\u00f4i tr\u01b0\u1eddng aprotonic, xeton th\u01a1m t\u1ea1o anion g\u1ed1c b\u1ec1n, c\u00f3 m\u00e0u, trong \u0111\u00f3 \u0111i\u1ec7n t\u00edch \u00e2m t\u1eadp trung \u1edf oxi, c\u00f2n electron \u0111\u1ed9c th\u00e2n \u1edf nguy\u00ean t\u1eed cacbon : Ar Na ho\u1eb7c K Ar Na+ c=0 ete ho\u1eb7c THF \\\\ c -o Ar Ar Xetyl Anion g\u1ed1c nh\u01b0 th\u1ebf c\u00f3 t\u00ean th\u00f4ng th\u01b0\u1eddng l\u00e0 xetyl. T\u00ednh b\u1ec1n c\u1ee7a anion g\u1ed1c c\u1ee7a xeton th\u01a1m l\u00e0 do s\u1ef1 gi\u1ea3i t\u1ecfa electron \u0111\u1ed9c th\u00e2n v\u00e0o hai v\u00f2ng benzen. Anion g\u1ed1c c\u1ee7a xeton th\u01a1m b\u00e9o v\u00e0 \u0111\u1eb7c bi\u1ec7t l\u00e0 xeton d\u00e3y b\u00e9o v\u00e0 xeton v\u00f2ng c\u00f3 t\u00ednh b\u1ec1n k\u00e9m h\u01a1n nhi\u1ec1u v\u00e0 d\u1ec5 d\u00e0ng \u0111ime h\u00f3a t\u1ea1o th\u00e0nh ancolat 1 ,2 -\u0111iol. Ph\u1ea3n \u1ee9ng n\u00e0y c\u00f3 t\u00ean \u0111im\u00e9 h\u00f3a kh\u1eed pinacolic xeton. T\u1eeb xeton \u0111\u01a1n gi\u1ea3n nh\u1ea5t l\u00e0 axeton s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c pinacol (1,2-\u0111iol). Ch\u1ea5t kh\u1eed th\u01b0\u1eddng d\u00f9ng l\u00e0 kim lo\u1ea1i h\u00f3a tr\u1ecb hai nh\u01b0 Mg, Zn ho\u1eb7c h\u1ed7n h\u1ed1ng c\u1ee7a ch\u00fang, trong dung m\u00f4i aprotonic \u00edt ph\u00e2n c\u1ef1c nh\u01b0 benzen, toluen, metylen \u0111iclorua s\u1ebd x\u1ea3y ra ph\u1ea3n \u1ee9ng \u0111ime h\u00f3a anion - g\u1ed1c : 395","h 3c H .,c \\\\ \u0111ime h\u00f3a h 3c c h 3 \\\\ \u2022 \u201d \\\\ 7. x c =0 \/ C- 0 Mg - - -> c-c benzen H3C\u1ef5 \u1ecb\u00ec, \u1ecb1yN CH3 \/ H90 H ;C H+ \\\\\/ H,c Mg h 3c c h 3 c-c \/ 1 1\\\\ h 3c OH OH CH Pinacol (43 - 50%) Ng\u01b0ng t\u1ee5 axyloin c\u1ee7a este v\u1ec1 c\u01a1 ch\u1ebf c\u0169ng t\u01b0\u01a1ng t\u1ef1 nh\u01b0 ph\u1ea3n \u1ee9ng kh\u1eed pinacolic, n\u00f3 g\u1ed3m m\u1ed9t v\u00e0i giai \u0111o\u1ea1n k\u1ebf ti\u1ebfp nhau c\u1ee7a s\u1ef1 t\u1ea1o th\u00e0nh anion - g\u1ed1c v\u00e0 anion. S\u1ea3n ph\u1ea9m cu\u1ed1i c\u1ee7a ph\u1ea3n \u1ee9ng l\u00e0 \u0111ianion 1 ,2 -xeton, \u0111\u00f3 l\u00e0 en\u0111iolat sau khi proton h\u00f3a s\u1ebd chuy\u1ec3n th\u00e0nh a-hi\u0111roxixeton, \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 axyloin. Th\u00ed d\u1ee5 : o o Na+ a) 2 R - C OEt OEt Anion g\u1ed1c \u01a1 Na \u0111i me h\u00f3a EtO OEt \/ \\\\ _ _\/ b) 2 R - C R -C -C -R \u01a0Et \u0129_ I 0 ; 0- Na Na E*tcCV) y OEt R\u2014c c) I I\u2014r\u00ecC -R R -C -C -R + 2EtONa 2Na+ \u00b0Na+ \u0129F oo d) R\u2014C \u2014C \u2014R + 2Na o Na o Na+ \u0129 l\u00ed R -\u1edf ' I oo R -C R -C o Na o Na+ \u0110ianion 1,2-\u0111ixeton (en\u0111iolat) o Na CH3COOH R \u2014c OH -> R - C - C H - R II I R -C I OH 0 OH e) R - CI \\\\ R -C Axyloin o Na 396","S\u1ef1 t\u1ea1o th\u00e0nh axyloin khi kh\u1eed este c\u1ee7a axit cacboxylic d\u00e3y b\u00e9o b\u1eb1ng natri trong dung m\u00f4i tr\u01a1 \u0111\u00e3 \u0111\u01b0\u1ee3c Bouveault v\u00e0 Blanc quan s\u00e1t th\u1ea5y \u0111\u1ea7u ti\u00ean v\u00e0o n\u0103m 1903. 2R \u2014C \u2014OEt ---e-te--, -0--c--,-3-----5--n--g-\u00e0-y-- > R -C -C H -R II II \u1ecb 0 0 OH (50 - 75%) Ph\u1ea3n \u1ee9ng n\u00e0y ch\u01b0a t\u00ecm th\u1ea5y \u1ee9ng d\u1ee5ng trong h\u00f3a h\u1eefu c\u01a1 cho \u0111\u1ebfn n\u00e3m 1947 khi Stoll v\u00e0 Prelog d\u00f9ng n\u00f3 \u0111\u1ec3 t\u1ed5ng h\u1ee3p h\u1ee3p ch\u1ea5t v\u00f2ng cacbon v\u1edbi s\u1ed1 nguy\u00ean t\u1eed c trung b\u00ecnh (C8- C |3) ho\u1eb7c k\u00edch th\u01b0\u1edbc v\u00f2ng l\u1edbn t\u1eeb \u0111ieste c\u1ee7a axit a,co-\u0111icacboxylic. Th\u1ef1c ra, ph\u1ea3n \u1ee9ng axyloin h\u00f3a l\u00e0 ph\u01b0\u01a1ng ph\u00e1p t\u1ed1t nh\u1ea5t v\u00e0 tri\u1ec3n v\u1ecdng nh\u1ea5t \u0111\u1ec3 t\u1ed5ng h\u1ee3p v\u00f2ng l\u1edbn c\u00f3 t\u1eeb t\u00e1m nguy\u00ean t\u1eed cacbon tr\u1edf l\u00ean. \u0110ieste c\u1ee7a axit a,(\u1ee9-\u0111icacboxylic trong xilen s\u00f4i \u0111\u01b0\u1ee3c tr\u1ed9n l\u1eabn v\u1edbi natri t\u00e1n nh\u1ecf trong d\u00f2ng agon \u0111\u1ec3 ng\u0103n s\u1ef1 t\u1ea1o th\u00e0nh natri oxit, anion - g\u1ed1c v\u00e0 \u0111ianion trung gian. \u0110\u1ec3 \u0111\u1ea1t t\u1edbi hi\u1ec7u su\u1ea5t th\u1ecfa \u0111\u00e1ng c\u1ee7a axyloin c\u1ea7n ph\u1ea3i khu\u1ea5y m\u1ea1nh v\u1edbi v\u1eadn t\u1ed1c 3.000 - 10.000 v\u00f2ng\/ph\u00fat. V\u1edbi axyloin v\u00f2ng l\u1edbn c\u00f3 t\u1eeb 15C tr\u1edf l\u00ean, hi\u1ec7u su\u1ea5t \u0111\u1ea1t \u0111\u1ebfn 90 - 95% : Na ^C =0 CH30 - C - ( C H 2) 1 6 - C -\u20140 Co cHh 3 \u2014\u2014\u2014 - > (CH2) 16 , II II xiilleenn, 14U v \\\\ c H \u2014OH oo (96%) \u0110\u1ed1i v\u1edbi v\u00f2ng trung b\u00ecnh, hi\u1ec7u su\u1ea5t 2-hi\u0111roxixeton \u00edt khi th\u1ea5p h\u01a1n 50% : r^^^C O O C H 3 Na ^ ^ \/C O O C H 3 xilen, 140\u00b0c > \u0110imetyl xebaxinat 2-Oxoxiclo\u0111ecanol (6 6 %) \u0110\u1ed1i v\u1edbi c\u00e1c \u0111ieste c\u1ee7a axit cacboxylic th\u1ea5p th\u00ec ng\u01b0ng t\u1ee5 axyloin s\u1ebd c\u1ea1nh tranh v\u1edbi ng\u01b0ng t\u1ee5 \u0110ichman khi t\u1ea1o th\u00e0nh v\u00f2ng 5, 6 c\u1ea1nh. Ng\u01b0ng t\u1ee5 axyloin c\u1ea7n t\u1ed1i thi\u1ec3u 4 \u0111\u01b0\u01a1ng l\u01b0\u1ee3ng Na, trong khi \u0111\u00f3 \u0111\u00f3ng v\u00f2ng \u0110ichman ch\u1ec9 c\u1ea7n 1 \u0111\u01b0\u01a1ng l\u01b0\u1ee3ng Na ho\u1eb7c d\u00f9ng natri ancolat. Vi\u1ec7c ti\u1ebfn h\u00e0nh ph\u1ea3n \u1ee9ng khi s\u1eed d\u1ee5ng trimetylclosilan th\u00ec ho\u00e0n to\u00e0n lo\u1ea1i tr\u1eeb ng\u01b0ng t\u1ee5 \u0110ichman v\u00e0 hi\u1ec7n nay \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng nhi\u1ec1u : \/ COOCH3 Na, M e3SiCl ^ C \u2014OSiMe3 (c H2)n \u00bb (CH2)n II > COOCH3 Xllen c \u2014OSiMe3 -^ 2 ^ (C \u201e < r (CH2< i . : \u00b0 CH -O H CH2 n = 2 - 27 C\u00e1c an\u0111ehit b\u00e9o kh\u00f4ng no c\u00f3 Ha khi c\u00f3 m\u1eb7t KCN th\u01b0\u1eddng tham gia ph\u1ea3n \u1ee9ng axyloin h\u00f3a. \u0110\u1eadc bi\u1ec7t, \u00ed\u00f2man\u0111ehit khi c\u00f3 m\u1eb7t Ca(OH)2 c\u00f3 th\u1ec3 axyloin h\u00f3a th\u00e0nh a-hi\u0111roxiaxetan\u0111ehit, nh\u01b0ng s\u1ea3n ph\u1ea9m n\u00e0y l\u1ea1i an\u0111ol h\u00f3a ngay th\u00e0nh h\u1ed7n h\u1ee3p hexoz\u01a1 g\u1ecdi l\u00e0 fomo : 397","HCHO + HCHO,>y'\u00b0inll\u00d3a- > HOCH2-C H O 3HOCH2CHO Mdolh6a > C6H |20 6 Butlerop l\u00e0 ng\u01b0\u1eddi \u0111\u1ea7u ti\u00ean th\u1ef1c hi\u1ec7n ph\u1ea3n \u1ee9ng n\u00e0y v\u00e0o n\u0103m 1879. 14.15 C\u1ed9ng li\u00ean h\u1ee3p : ph\u1ea3n \u1ee9ng Maic\u01a1n (Michael) H\u1ee3p ch\u1ea5t cacbonyl a,P-kh\u00f4ng no th\u01b0\u1eddng c\u00f3 ho\u1ea1t t\u00ednh \u1edf li\u00ean k\u1ebft \u0111\u00f4i. Cacbon p c\u00f3 t\u00ednh electrophin v\u00ec n\u00f3 \u0111\u01b0\u1ee3c chia m\u1ed9t ph\u1ea7n \u0111i\u1ec7n t\u00edch d\u01b0\u01a1ng c\u1ee7a cacbon cacbonyl do s\u1ef1 c\u1ed9ng h\u01b0\u1edfng : o 0\u201c c f H \/C * H ^+ ^ \/ C = C ^ CH 3 <-----> \/ C = C ^ CH3 <-----> \/ C ~ C \\\\ CH HH HH HH T\u00e1c nh\u00e2n nucleophin c\u00f3 th\u1ec3 t\u1ea5n c\u00f4ng h\u1ee3p ch\u1ea5t cacbonyl a,p-kh\u00f4ng no ho\u1eb7c v\u00e0o nh\u00f3m cacbonyl ho\u1eb7c v\u00e0o v\u1ecb tr\u00ed [3. Khi s\u1ef1 t\u1ea5n c\u00f4ng th\u1ef1c hi\u1ec7n \u1edf nh\u00f3m cacbonyl, s\u1ef1 proton h\u00f3a oxi d\u1eabn \u0111\u1ebfn s\u1ea3n ph\u1ea9m c\u1ed9ng 1,2 trong \u0111\u00f3 t\u00e1c nh\u00e2n nucleophin v\u00e0 proton c\u1ed9ng v\u00e0o c\u00e1c nguy\u00ean t\u1eed c\u1ea1nh nhau. Khi s\u1ef1 c\u1ed9ng h\u1ee3p \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n \u1edf v\u1ecb tr\u00ed p, nguy\u00ean t\u1eed oxi l\u00e0 nguy\u00ean t\u1eed th\u1ee9 4 t\u00ednh t\u1eeb v\u1ecb tr\u00ed nucleophin v\u00e0 s\u1ef1 c\u1ed9ng h\u1ee3p n\u00e0y g\u1ecdi l\u00e0 c\u1ed9ng 1,4. C\u1ed9ng 1,2 : o 'N O -H Nuc \\\\ 1 . Nuc _ Nug: \/C = cT S u t, H k ch3 ch3\u00ed= ^ ch3 \u00ab= * ^c= c^ HH HH HH T\u1ea5n c\u00f4ng nh\u00f3m cacbonyl Proton h\u00f3a ankoxit C\u1ed9ng 1,4 : c\u1ed9ng Maic\u01a1rt > \u201e V\\\\ Nuc v \\\\ ^ H+ CH3 i= \u00b1 N u c - C - C ^ CH3 T = T\u1ea5n c\u00f4ng Cp HH Proton h\u00f3a enolat <=^ \u1edd \u2014H \u1ecc H1 H\u1eaa \\\\^ \\\\ \/ CJ\\\\ _ N u c - c - c t ' CH3 N u c - C - C \\\" CH3 HH H HH (enol) (xeto) Tautome h\u00f3a Ph\u1ea3n \u1ee9ng c\u1ed9ng h\u1ee3p ion malonat v\u00e0o este c\u1ee7a axit xinamic \u0111\u01b0\u1ee3c Maic\u01a1n ph\u00e1t hi\u1ec7n n\u0103m 1887, v\u00ec th\u1ebf ki\u1ec3u c\u1ed9ng h\u1ee3p t\u00e1c nh\u00e2n nucleophin n\u00e0y \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 ph\u1ea3n \u1ee9ng Maic\u01a1n : 398","C6H5CH = CH\u2014c \u2014OEt + CH(COOEt)2 C6H5CHCH2COOEt 0 CH(COOEt)2 (72%) \u0110\u1ea7u ti\u00ean, ng\u01b0\u1eddi ta g\u1ecdi s\u1ef1 c\u1ed9ng h\u1ee3p 1,4 ion enolat c\u1ee7a h\u1ee3p ch\u1ea5t 1 ,3 -\u0111icacbonyl v\u00e0o h\u1ee3p ch\u1ea5t cacbonyl a , [3-kh\u00f4ng no l\u00e0 ph\u1ea3n \u1ee9ng Maic\u01a1n : Hr\u1ecc X I ,3 n\u201e \/ C = C^- C - R 3 , ______ T ^ R -C -C H .-C -R 2 > R -C -C H -C -R 2 <= \u00b1 II 2 II II II oo oo <-=\u00bb R I\u2014 c \u2014CH\u2014 c1 \u2014C^H \u2014c \u2014R1 <B=H \u00b1 \u1ecbR 1\u2014 c \u2014CH \u2014c1 \u2014CH2\u2014c \u2014R3 1 Uo\u0129 1*1 Uol I o cT o o cT , o R R lon enolat \u0111\u01b0\u1ee3c t\u1ea1o th\u00e0nh do c\u1ed9ng h\u1ee3p 1,4 \u0111\u01b0\u1ee3c b\u1ec1n h\u00f3a nh\u1edd gi\u1ea3i t\u1ecfa \u0111i\u1ec7n t\u00edch v\u00e0o n\u1ed1i \u0111\u00f4i, trong khi \u0111\u00f3 s\u1ea3n ph\u1ea9m c\u1ed9ng h\u1ee3p 1,2 kh\u00f4ng \u0111\u01b0\u1ee3c b\u1ec1n h\u00f3a nh\u1edd li\u00ean h\u1ee3p. Do \u0111\u00f3 s\u1ea3n ph\u1ea9m c\u1ed9ng h\u1ee3p 1,4 v\u1ec1 m\u1eb7t nhi\u1ec7t \u0111\u1ed9ng h\u1ecdc b\u1ec1n h\u01a1n \u0111\u1ed3ng ph\u00e2n c\u1ee7a n\u00f3 l\u00e0 s\u1ea3n ph\u1ea9m c\u1ed9ng h\u1ee3p 1,2. Ng\u00e0y nay, l\u0129nh v\u1ef1c \u1ee9ng d\u1ee5ng ph\u1ea3n \u1ee9ng Maic\u01a1n \u0111\u01b0\u1ee3c m\u1edf r\u1ed9ng l\u00e0 nh\u1edd ion enolat c\u1ee7a xeton v\u00e0 enamin l\u00e0m t\u00e1c nh\u00e2n nucleophin (\u201cch\u1ea5t cho Maic\u01a1n\u201d) v\u00e0 c\u00e1c \u201cch\u1ea5t nh\u1eadn Maic\u01a1n\u201d kh\u00e1c nhau l\u00e0 h\u1ee3p ch\u1ea5t a , P-kh\u00f4ng no c\u1ee7a xeton, an\u0111ehit, este, nitrin, h\u1ee3p ch\u1ea5t nitro, h\u1ee3p ch\u1ea5t sunfo. M\u1ed9t v\u00e0i th\u00ed d\u1ee5 c\u1ed9ng h\u1ee3p ion enolat v\u00e0o h\u1ee3p ch\u1ea5t a , p-kh\u1ed3ng no c\u1ee7a xeton, este v\u00e0 nitrin \u0111\u01b0\u01a1c d\u1eabn ra d\u01b0\u1edbi \u0111\u00e2y : oo ( y 3 + c h 2 = c h - c - c 6h 5 (^C \u1ea1C H ^C O Q H , 0 (64%) H 3C \\\\ _FtONa F_tD_ HH3C J C\\\\ H2\/COOE\u201dt CH2(COOEt)2 + = C H \u2014COOEt >\u1ef5 C ^ H3C 25 c H3C CH(COOEt)2 (70%) CH3COCH2COCH3 + 2CH2=CHCN FuN EtOH n c c h 2c h 2 c h 2c h 2c n ^\/ c' h 3c - c c - c h 3 ' I0 I \u1ecf (77%) 27- H H CT2 399","B\u1eb1ng ph\u1ea3n \u1ee9ng c\u1ed9ng Maic\u01a1n gi\u1eefa ion enolat c\u1ee7a este malonat v\u1edbi metyl vinyl xeton, ti\u1ebfp theo ti\u1ebfn h\u00e0nh thu\u1ef7 ph\u00e2n v\u00e0 \u0111ecacboxyl h\u00f3a ta s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c \u00f4-xetoaxit: COOEt COOEt H \u1ecc ^ 1 EtO OC-CH o HI w H -C HOH I \/ C = C - C H 3 cH \u2014OEt * H C - C - C H , <: \u00b1 EtOOC \u2014CH \u2014c 1 H COOEt o H+, tA) COOH o 1 II \u00b1 EtOOC \u2014c h c h 2c h 2c \u2014c h 3 H ,0 1\u0129 (90%) H O O C - c h c h 2c h 2c - c h 3 Axit malonic th\u1ebf \u1ecci \u1ecc\u0129 \u25a0> H O - C ~ C H 2CH2CH2 - C ~ C H 3 5-xetoaxit 14.16 \u0110\u00f3ng v\u00f2ng Robins\u01a1n Ch\u00fang ta \u0111\u00e3 bi\u1ebft ph\u1ea3n \u1ee9ng c\u1ed9ng Maic\u01a1n c\u1ee7a enolat xeton (ho\u1eb7c enamin) v\u1edbi xeton a , (3-kh\u00f4ng no t\u1ea1o th\u00e0nh \u00f4-\u0111ixeton. N\u1ebfu c\u1ed9ng li\u00ean h\u1ee3p x\u1ea3y ra \u1edf m\u00f4i tr\u01b0\u1eddng baz\u01a1 m\u1ea1nh ho\u1eb7c axit m\u1ea1nh th\u00ec \u00f4-\u0111ixeton s\u1ebd ng\u01b0ng t\u1ee5 an\u0111ol n\u1ed9i ph\u00e2n t\u1eed, k\u00e8m theo \u0111ehi\u0111rat h\u00f3a s\u1ebd cho ta m\u1ed9t v\u00f2ng 6 c\u1ea1nh m\u1edbi, \u0111\u00f3 l\u00e0 xiclohexenon li\u00ean h\u1ee3p. Ph\u1ea3n \u1ee9ng n\u00e0y \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 ph\u1ea3n \u1ee9ng \u0111\u00f3ng v\u00f2ng Robins\u01a1n. H\u00e3y x\u00e9t th\u00ed d\u1ee5 d\u00f9ng xiclohexanon th\u1ebf l\u00e0m ch\u1ea5t cho Maic\u01a1n v\u00e0 metyl vinyl xeton (MVX) l\u00e0m ch\u1ea5t nh\u1eadn Maic\u01a1n, ta c\u00f3 ph\u1ea3n \u1ee9ng \u0111\u00f3ng v\u00f2ng Robins\u01a1n nh\u01b0 sau : a och 3 CH CH ch\/ S > (65%) Ph\u1ea3n \u1ee9ng b\u1eaft \u0111\u1ea7u b\u1eb1ng s\u1ef1 c\u1ed9ng enolat c\u1ee7a xiclohexanon v\u00e0o MVX \u0111\u1ec3 h\u00ecnh th\u00e0nh \u00f4-\u0111ixeton. Giai \u0111o\u1ea1n I : C\u1ed9ng Maic\u01a1n ch3^ _ ^ H \/H CH3 CH3 _ 1 0c h 3' \u00e8 - Qo H OH H t\u1ef8 i ch3 o o \u00d4-\u0110ixeton CH, o 400","\u00d4-\u0110ixeton c\u00f3 th\u1ec3 tham gia ng\u01b0ng t\u1ee5 an\u0111ol theo nhi\u1ec1u h\u01b0\u1edbng kh\u00e1c nhau, nh\u01b0ng thu\u1eadn l\u1ee3i nh\u1ea5t ch\u1ec9 c\u1ed5 m\u1ed9t, \u0111\u00f3 l\u00e0 h\u00ecnh th\u00e0nh v\u00f2ng 6 c\u1ea1nh. \u0110\u1ec3 h\u00ecnh th\u00e0nh v\u00f2ng 6 th\u00ec enolat c\u1ee7a metylxeton t\u1ea5n c\u00f4ng v\u00e0o nh\u00f3m cacbonyl c\u1ee7a xiclohexanon. s\u1ea3n ph\u1ea9m an\u0111ol \u0111\u01b0\u1ee3c \u0111ehi\u0111rat h\u00f3a s\u1ebd cho xiclohexenon. Giai \u0111o\u1ea1n 2 : An\u0111ol h\u00f3a \u0111\u00f3ng v\u00f2ng HO v H -O H Giai \u0111o\u1ea1n 3 : \u0110ehi\u0111rat h\u00f3a o- + OH B\u1eb1ng ph\u01b0\u01a1ng ph\u00e1p n\u00e0y ng\u01b0\u1eddi ta c\u00f3 th\u1ec3 t\u1ed5ng h\u1ee3p hocmon estron : ch\u1ea5t nh\u1eadn Maic\u01a1n ch\u1ea5t cho Maic\u01a1n 1) \u0111\u00f3ng v\u00f2ng 2 ) \u0111emetyl h\u00f3a Estron 401","Ch\u01b0\u01a1ng 15 H\u1ee2P CH\u1ea4T D\u1eca V\u00d2NG H\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng l\u00e0 nh\u1eefng h\u1ee3p ch\u1ea5t c\u00f3 ch\u1ee9a h\u1ec7 v\u00f2ng, trong v\u00f2ng \u0111\u00f3, ngo\u00e0i cacbon c\u00f2n c\u00f3 nguy\u00ean t\u1eed c\u1ee7a c\u00e1c nguy\u00ean t\u1ed1 kh\u00e1c n\u1eefa nh\u01b0 nit\u01a1, oxi, l\u01b0u hu\u1ef3nh, ... m\u00e0 ta th\u01b0\u1eddng g\u1ecdi l\u00e0 d\u1ecb nguy\u00ean t\u1eed hay d\u1ecb t\u1eed. C\u00e1c h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng l\u00e0 m\u1ed9t ch\u01b0\u01a1ng l\u1edbn, quan tr\u1ecdng v\u00e0 ph\u00e1t tri\u1ec3n m\u1ea1nh c\u1ee7a h\u00f3a h\u1ecdc h\u1eefu c\u01a1. Ch\u00fang ph\u00e2n b\u1ed1 r\u1ed9ng r\u00e3i trong thi\u00ean nhi\u00ean. Nhi\u1ec1u ch\u1ea5t gi\u1eef vai tr\u00f2 quan tr\u1ecdng trong c\u01a1 th\u1ec3 s\u1ed1ng nh\u01b0 c\u00e1c baz\u01a1 nit\u01a1 c\u1ee7a axit nucleic l\u00e0 nh\u1eefng h\u1ec7 d\u1ecb v\u00f2ng pyrimi\u0111in v\u00e0 purin ; clorophin trong c\u00e2y xanh v\u00e0 heme trong hemoglobin c\u1ee7a m\u00e1u l\u00e0 nh\u1eefng d\u1eabn xu\u1ea5t c\u1ee7a h\u1ec7 v\u00f2ng porphyrin ; c\u00e1c vitamin nh\u01b0 thiamin (vitamin B\u1ecb), nicotinamit (vitamin B3), axit ascobic (vitamin C ) ,... \u0111\u1ec1u l\u00e0 c\u00e1c h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng. C\u00e1c h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng c\u00f3 vai tr\u00f2 quan tr\u1ecdng trong c\u00e1c chu tr\u00ecnh trao \u0111\u1ed5i ch\u1ea5t, c\u00f3 ho\u1ea1t t\u00ednh sinh h\u1ecdc cao, v\u00ec v\u1eady ph\u1ea7n l\u1edbn c\u00e1c thu\u1ed1c ch\u1eefa b\u1ec7nh c\u00f3 ch\u1ee9a trong ph\u00e2n t\u1eed c\u00e1c d\u1ecb v\u00f2ng. \u0110i\u1ec1u \u0111\u00f3 gi\u1ea3i th\u00edch v\u00ec sao hi\u1ec7n nay h\u01a1n m\u1ed9t n\u1eeda s\u1ed1 c\u00f4ng tr\u00ecnh khoa h\u1ecdc c\u00f4ng b\u1ed1 trong c\u00e1c t\u1ea1p ch\u00ed v\u1ec1 h\u00f3a h\u1ecdc h\u1eefu c\u01a1 l\u00e0 thu\u1ed9c v\u1ec1 c\u00e1c h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng. Hi\u1ec7n nay ng\u01b0\u1eddi ta \u0111\u00e3 bi\u1ebft \u0111\u01b0\u1ee3c c\u00e1c h\u1ec7 v\u00f2ng c\u00f3 ch\u1ee9a nhi\u1ec1u nguy\u00ean t\u1ed1 c\u1ee7a b\u1ea3ng tu\u1ea7n ho\u00e0n, nh\u01b0ng \u0111\u01b0\u1ee3c ch\u00fa \u00fd nghi\u00ean c\u1ee9u nhi\u1ec1u nh\u1ea5t v\u1eabn l\u00e0 h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng n\u0103m v\u00e0 s\u00e1u c\u1ea1nh ch\u1ee9a c\u00e1c nguy\u00ean t\u1eed nit\u01a1, oxi v\u00e0 l\u01b0u hu\u1ef3nh. 15.1 P h \u00e2 n lo\u1ea1i C\u00f3 th\u1ec3 d\u00f9ng c\u00e1c c\u00e1ch sau \u0111\u00e2y \u0111\u1ec3 ph\u00e2n lo\u1ea1i h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng : - Theo k\u00edch th\u01b0\u1edbc c\u1ee7a v\u00f2ng : ta c\u00f3 v\u00f2ng ba, b\u1ed1n, n\u0103m, s\u00e1u v\u00e0 b\u1ea3y c\u1ea1nh. H\u1ee3p ch\u1ea5t v\u1edbi k\u00edch th\u01b0\u1edbc l\u1edbn h\u01a1n \u00edt g\u1eb7p (h\u1ee3p ch\u1ea5t v\u00f2ng l\u1edbn ki\u1ec3u ete crao th\u01b0\u1eddng kh\u00f4ng thu\u1ed9c v\u1ec1 h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng). Trong c\u00e1c th\u00ed d\u1ee5 d\u01b0\u1edbi \u0111\u00e2y ch\u00fang ta ch\u01b0a \u0111\u1ec1 c\u1eadp \u0111\u1ebfn c\u00e1ch g\u1ecdi t\u00ean m\u00e0 ch\u1ec9 ch\u00fa \u00fd \u0111\u1ebfn k\u00edch th\u01b0\u1edbc c\u1ee7a v\u00f2ng. HH H Theo ki\u1ec3u nguy\u00ean t\u1ed1 : ch\u1ee7 y\u1ebfu l\u00e0 c\u00e1c h\u1ee3p ch\u1ea5t ch\u1ee9a nit\u01a1, oxi v\u00e0 l\u01b0u hu\u1ef3nh. Ns 402","- Theo s\u00f4' c\u00e1c d\u1ecb t\u1eed : ph\u1ed5 bi\u1ebfn l\u00e0 m\u1ed9t ho\u1eb7c hai d\u1ecb t\u1eed, tuy v\u1eady ng\u01b0\u1eddi ta c\u0169ng bi\u1ebft c\u00f3 lo\u1ea1i ba ho\u1eb7c b\u1ed1n d\u1ecb t\u1eed trong v\u00f2ng. :> n N ^N N\u2014 N NN 1 HH i. Jn N N H H - Theo b\u1ea3n ch\u1ea5t v\u00e0 s\u1ef1 ph\u00e2n b\u1ed1 t\u01b0\u01a1ng h\u1ed7 c\u1ee7a m\u1ed9t v\u00e0i d\u1ecb t\u1eed. N -O On o o Theo m\u1ee9c \u0111\u1ed9 b\u00e3o h\u00f2a : d\u1ecb v\u00f2ng c\u00f3 th\u1ec3 th\u01a1m, ch\u01b0a no v\u00e0 no. N' N o H H\u00f3a h\u1ecdc c\u1ee7a d\u1ecb v\u00f2ng th\u01a1m \u0111\u01b0\u1ee3c nghi\u00ean c\u1ee9u t\u1ec9 m\u1ec9 nh\u1ea5t. D\u1ecb v\u00f2ng no ho\u1eb7c ch\u01b0a no, v\u1ec1 t\u00ednh ch\u1ea5t h\u00f3a h\u1ecdc kh\u00f4ng \u0111\u01b0\u1ee3c xem l\u00e0 h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng, m\u00e0 ch\u1ec9 l\u00e0 \u0111\u1ed3ng \u0111\u1eb3ng v\u00f2ng c\u1ee7a h\u1ee3p ch\u1ea5t b\u00e9o (ete, sunfua, amin b\u1eadc hai). - Theo s\u1ed1 v\u00f2ng : ph\u00e2n bi\u1ec7t h\u1ec7 \u0111\u01a1n v\u00f2ng, \u0111a v\u00f2ng (ch\u1ee7 y\u1ebfu g\u1ecdi l\u00e0 v\u00f2ng ng\u01b0ng t\u1ee5). S\u1ed1 v\u00f2ng v\u00e0 ki\u1ec3u v\u00f2ng c\u00f3 th\u1ec3 kh\u00e1c nhau. C ON N H 15.2 Danh ph\u00e1p d\u1ecb v\u00f2ng \u0111\u01a1n v\u00f2ng T\u00ean c\u1ee7a c\u00e1c h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng r\u1ea5t ph\u1ee9c t\u1ea1p l\u00e0 do s\u1ef1 kh\u00e1c nhau nhi\u1ec1u c\u1ee7a c\u00e1c ki\u1ec3u c\u1ea5u tr\u00fac d\u1ecb v\u00f2ng. M\u1eb7c d\u1ea7u \u0111\u1ea7u th\u1ebf k\u1ef7 20 \u0111\u00e3 x\u00e2y d\u1ef1ng h\u1ec7 t\u00ean g\u1ecdi ch\u00ednh th\u1ed1ng cho c\u00e1c h\u1ee3p ch\u1ea5t \u0111\u01a1n v\u00f2ng, nh\u01b0ng IUPAC v\u1eabn cho ph\u00e9p s\u1eed d\u1ee5ng t\u00ean th\u01b0\u1eddng v\u00e0 n\u1eeda h\u1ec7 th\u1ed1ng. 15.2.1 T\u00ean th\u01b0\u1eddng C\u00f3 kho\u1ea3ng 100 h\u1ee3p ch\u1ea5t \u0111\u01b0\u1ee3c d\u00f9ng t\u00ean th\u01b0\u1eddng nhi\u1ec1u h\u01a1n l\u00e0 t\u00ean h\u1ed9 th\u1ed1ng. Th\u01b0\u1eddng g\u1eb7p nh\u1ea5t l\u00e0 d\u1ecb v\u00f2ng 5, 6 c\u1ea1nh ch\u1ee9a 1 v\u00e0 2 d\u1ecb t\u1eed. - V\u00f2ng 5 c\u1ea1nh v\u1edbi 1 d\u1ecb t\u1eed : 43 \u1ee21 s N N N H H H Furan Thiophen Pyrol 2-Pyrolin Pyroli\u0111in* 403","V\u00f2ng 5 c\u1ea1nh v\u1edbi 2 d\u1ecb t\u1eed : \u1ee3. Q\u00bbNNI 1 \u1ee2 s11 NNi i t i o4 __3 HL \u0129 Ho 0o Thiazol 11 Pyrazol Imi\u0111azol Oxazol Isoxazol - V\u00f2ng 6 c\u1ea1nh v\u1edbi 1 d \u1ecb t\u1eed : N N 01 o H Pyri\u0111in 2H-Pyran 4H-Pyran Piperi\u0111in (a-Pyran) (y-Pyran) - V\u00f2ng 6 c\u1ea1nh v\u1edbi 2 d\u1ecb t\u1eed : Q; \u1eefN1 \u2019 \u1ed1 H aH N Pyri\u0111azin pyrim i\u0111in N1 \u1ed3N H M orpholin Pyrazin Piperazin Quy t\u1eafc IUPAC kh\u00f4ng quy \u0111\u1ecbnh v\u1ecb tr\u00ed c\u1ee7a d\u1ecb t\u1eed khi vi\u1ebft c\u00f4ng th\u1ee9c c\u1ee7a d\u1ecb v\u00f2ng, nh\u01b0ng th\u01b0\u1eddng d\u1ecb t\u1eed \u0111\u01b0\u1ee3c \u0111\u1eb7t ph\u00eda d\u01b0\u1edbi c\u00faa v\u00f2ng. Vi\u1ec7c d\u00e0nh s\u1ed1 nguy\u00ean t\u1eed c\u1ee7a h\u1ee3p ch\u1ea5t \u0111\u01a1n v\u00f2ng lu\u00f4n \u0111\u01b0\u1ee3c b\u1eaft \u0111\u1ea7u t\u1eeb d\u1ecb t\u1eed. N\u1ebfu d\u1ecb v\u00f2ng ch\u1ee9a c\u00e1c d\u1ecb t\u1eed kh\u00e1c nhau th\u00ec tu\u00e2n theo th\u1ee9 t\u1ef1 \u01b0u ti\u00ean sau : o > s > N. Ti\u1ebfp theo, d\u00e1nh s\u00f4 sao cho c\u1ea5c d\u1ecb t\u1eed c\u1ed1 locant nh\u1ecf nh\u1ea5t. Khi trong ph\u1ea7n t\u1eed c\u00f3 c\u00e1c nguy\u00ean t\u1eed nit\u01a1 kh\u00f4ng t\u01b0\u01a1ng \u0111\u01b0\u01a1ng nhau (= N - v\u00e0 - NH -) th\u00ec b\u1eaft \u0111\u1ea7u \u0111\u00e1nh s\u1ed1 \u1edf nguy\u00ean t\u1eed b\u00e3o h\u00f2a h\u01a1n. 15.2.2 T\u00ean h\u1ec7 th\u00f4ng \u0110\u1ed1i v\u1edbi h\u1ec7 \u0111\u01a1n v\u00f2ng ch\u1ee9a m\u1ed9t ho\u1eb7c m\u1ed9t v\u00e0i d\u1ecb t\u1eed trong v\u00f2ng ng\u01b0\u1eddi ta d\u00f9ng ph\u01b0cmg ph\u00e1p Hantzsch - VVidman. Theo ph\u01b0\u01a1ng ph\u00e1p n\u00e0y, t\u00ean g\u1ecdi d\u1ecb v\u00f2ng \u0111\u01b0\u1ee3c k\u1ebft h\u1ee3p c\u00e1c ti\u1ec1n t\u1ed1 \u201ca\u201d t\u01b0\u01a1ng \u1ee9ng : oxa \u0111\u1ed1i v\u1edbi nguy\u00ean t\u1eed oxi, thia \u0111\u1ed1i v\u1edbi nguy\u00ean t\u1eed l\u01b0u hu\u1ef3nh, aza \u0111\u1ed1i v\u1edbi nguy\u00ean t\u1eed nit\u01a1 v\u1edbi ph\u1ea7n c\u01a1 s\u1edf v\u00e0 h\u1eadu t\u1ed1 ph\u1ea3n \u00e1nh k\u00edch th\u01b0\u1edbc c\u00e1c v\u00f2ng (s\u1ed1 nguy\u00ean l\u1eed trong v\u00f2ng) v\u00e0 m\u1ee9c \u0111\u1ed9 no ho\u1eb7c kh\u00f4ng no c\u1ee7a v\u00f2ng (x. b\u1ea3ng 15.1). \u0110\u1ec3 cho d\u1ec5 \u0111\u1ecdc, \u0111\u00f4i khi ng\u01b0\u1eddi ta c\u00f3 th\u1ec3 b\u1ecf qua ch\u1eef \u201ca\u201d trong ti\u1ec1n t\u1ed1. Th\u00ed d\u1ee5 : l__ 2 V7 s N\u25a0 N V NI \u1ec9 I H H 0 tl\u00ecic tan 2 \u1ec9i-\u00ed\/zepin pehidror\/repin I \u00ed\/ziri\u0111in aviran -) K h \u00f4 n g d \u00f9 n g l\u00ean n \u00e0 y \u0111 \u1ec3 x \u00e2 y d \u1ef1 ng t\u00ean cho h\u1ec7 ng\u01b0ng t\u1ee5 404","Trong t\u00ean g\u1ecdi azepin d\u1eabn ra \u1edb tr\u00ean, k\u00fd hi\u1ec7u \u201cH\u201d (c\u00f3 ngh\u0129a l\u00e0 hi\u0111ro) \u0111\u01b0\u1ee3c d\u00f9ng \u0111\u1ec3 ch\u00ednh x\u00e1c h\u00f3a v\u1ecb tr\u00ed c\u1ee7a n\u1ed1i \u0111\u00f4i irong h\u1ec7 v\u1edbi s\u1ed1 c\u1ef1c \u0111\u1ea1i c\u1ee7a n\u1ed1i \u0111\u00f4i c\u00e1ch. Locant \u201cnh\u1eadn bi\u1ebft hi\u0111ro\u201d ch\u1ec9 ra r\u1eb1ng, nguy\u00ean t\u1eed hi\u0111ro \u201cd\u01b0 th\u1eeba\u201d \u1edf v\u1ecb tr\u00ed 2 , trong khi \u0111\u00f3 \u1edf c\u00e1c \u0111\u1ed3ng ph\u00e2n c\u1ee7a azepin, ngh\u0129a l\u00e0 trong c\u00e1c h\u1ee3p ch\u1ea5t v\u1edbi s\u1ef1 ph\u00e2n b\u1ed1 c\u00e1ch kh\u00e1c c\u1ee7a n\u1ed1i \u0111\u00f4i, n\u00f3 c\u00f3 th\u1ec3 \u1edf v\u1ecb tr\u00ed 1, 3, ho\u1eb7c 4. B \u1ea3 n g 15.1 Ph\u1ea7n c\u01a1 s\u1edf v\u00e0 h\u1eadu t\u1ed1 c\u1ee7a d\u1ecb v\u00f2ng S\u1ed1 nguy\u00ean t\u1eed V\u00f2ng ch\u1ee9a nit\u01a1 V\u00f2ng kh\u00f4ng ch\u1ee9a nit\u01a1 trong v\u00f2ng Kh\u00f4ng no + th\u01a1m No Kh\u00f4ng no + th\u01a1m No 3 4 - irin - iri\u0111in - iren - iran 5 - et - eti\u0111in - et - etan 6 - ol - oli\u0111in - ol - olan 7 - in * - epin * - in - an 8 - oxin * - epin - epan - oxin - okan \u2019 Kh\u00f4ng c\u00f3 h\u1eadu t\u1ed1 t\u01b0\u01a1ng \u1ee9ng m\u00e0 phd\u00ec th\u00eam li\u1ec1n t\u1ed1peh i\u0111ro v\u00e0o l\u00ean d\u1ecb v\u00f2ng kh\u00f4ng no ho\u1eb7c th\u01a1m. Khi c\u00f3 nhi\u1ec1u d\u1ecb nguy\u00ean t\u1eed c\u00f9ng lo\u1ea1i trong m\u1ed9t d\u1ecb v\u00f2ng th\u00ec d\u00f9ng th\u00eam c\u00e1c ti\u1ec1n t\u00f4' \u0111i-, tri-, tetra-, ... Locant c\u1ee7a c\u00e1c d\u1ecb t\u1eed \u0111\u01b0\u1ee3c \u0111\u1eb7t tr\u01b0\u1edbc ti\u1ec1n t\u1ed1 v\u1edbi g\u1ea1ch n\u1ed1i (-). N\u1ebfu c\u00f3 c\u00e1c d\u1ecb nguy\u00ean t\u1eed kh\u00e1c nhau trong m\u1ed9t d\u1ecb v\u00f2ng th\u00ec t\u1ed5 h\u1ee3p c\u00e1c ti\u1ec1n t\u1ed1 \u201ca\u201d theo th\u1ee9 t\u1ef1 gi\u1ea3m m\u1ee9c \u0111\u1ed9 \u01b0u ti\u00ean o > s > N : 4 4 n- n n- n 5 :\u1ecc .s ir N a \u1ecd .\u1ecc \u1ecd. T I H T 1,4-\u0110ioxan 1,2,4-Triazin lH-Tetrazol l,3,4-Thiadiazol T\u00ean g\u1ecdi c\u1ee7a g\u1ed1c h\u00f3a tr\u1ecb m\u1ed9t c\u1ee7a h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng th\u01b0\u1eddng \u0111\u01b0\u1ee3c h\u00ecnh th\u00e0nh b\u1eb1ng c\u00e1ch th\u00eam h\u1eadu t\u1ed1 -yl v\u00e0o t\u00ean th\u00f4ng th\u01b0\u1eddng ho\u1eb7c t\u00ean h\u1ec7 th\u1ed1ng c\u1ee7a h\u1ee3p ch\u1ea5t ban \u0111\u1ea7u. Tuy nhi\u00ean, t\u1ed5n t\u1ea1i c\u00e1c ngo\u1ea1i tr\u1eeb sau : furyl (\u0111\u1ed1i v\u1edbi furan), thienyl (\u0111\u1ed1i v\u1edbi thiophen), pyri\u0111yl, quinolyl, isoquinolyl. Trong t\u1ea5t c\u1ea3 c\u00e1c tr\u01b0\u1eddng h\u1ee3p, v\u1ecb tr\u00ed h\u00f3a tr\u1ecb t\u1ef1 do \u0111\u01b0\u1ee3c bi\u1ec3u th\u1ecb b\u1eb1ng locant xu\u1ea5t ph\u00e1t t\u1eeb quy t\u1eafc \u0111\u00e1nh s\u00f4' d\u1ecb v\u00f2ng : \u1ed9 \u1ecd- \u1ee2 H ' 2-Furyl 3-Thienyl Pyrazol-5-yl 2H-Pyran-6-yl G\u1ed1c c\u00f3 h\u00f3a tr\u1ecb t\u1ef1 do \u1edf nguy\u00ean t\u1eed nit\u01a1 \u0111\u01b0\u1ee3c g\u1ecdi t\u01b0\u01a1ng t\u1ef1 nh\u01b0 g\u1ed1c amin, c\u1ee5 th\u1ec3 l\u00e0 th\u00eam ch\u1eef \u201co\u201d v\u00e0o t\u00ean g\u1ecdi d\u1ecb v\u00f2ng : [> - \/\\\\ 1^ 2 \u1ed0 ^N - 4N x 1 Aziri\u0111ino- Morpholino- 67 lH-l,4-\u0110iazepino- 405","15.3 Danh ph\u00e1p h\u1ec7 d\u1ecb v\u00f2ng ng\u01b0ng t\u1ee5 15.3.1 T\u00ean th\u01b0\u1eddng M\u1ed9t s\u1ed1 h\u1ec7 d\u1ecb v\u00f2ng ng\u01b0ng t\u1ee5 \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng t\u00ean th\u00f4ng th\u01b0\u1eddng d\u01b0\u1edbi \u0111\u00e2y : Quinolin Isoquinolin 6 . H? 1 NT ^ N 7 Cromen \u00ab \/>s (\u0111\u1ed3ng ph\u00e2n 2H) Nt N , H .0 1 3 654 Purin Phenothiazin (\u0111\u1ed3ng ph\u00e2n 7H) q M9 10 1 6N 4 5 Phenazin 15.3.2 T\u00ean h\u1ec7 th\u1ed1ng T\u00ean h\u1ec7 th\u1ed1ng r\u1ea5t ph\u1ee9c t\u1ea1p v\u00ec v\u1eady ch\u00fang ta ch\u1ec9 \u0111\u1ec1 c\u1eadp \u0111\u1ebfn d\u1ea1ng chung nh\u1ea5t. Trong tr\u01b0\u1eddng h\u1ee3p \u0111\u01a1n gi\u1ea3n, \u1edf h\u1ec7 bixiclic khi d\u1ecb v\u00f2ng ng\u01b0ng t\u1ee5 v\u1edbi v\u00f2ng benzen (th\u01b0\u1eddng g\u1eb7p) th\u00ec t\u00ean g\u1ecdi xu\u1ea5t ph\u00e1t t\u1eeb t\u00ean d\u1ecb v\u00f2ng c\u1ed9ng th\u00eam ti\u1ec1n t\u1ed1 benzo- ho\u1eb7c benz- (n\u1ebfu ch\u1eef li\u1ec1n l\u00e0 nguy\u00ean \u00e2m). Th\u00ed d\u1ee5 : \u2014 N' 8 \u1ea2+ X X 54 l,4-Benzo\u0111iaz\u1eb9pin (\u0111\u1ed5ng ph\u1ea3n N, 0 Cation l-benzopirili H 1 Benzimi\u0111azol Benzofuran (cumaron) Khi c\u00f3 nhi\u1ec1u c\u00e1ch gh\u00e9p n\u1ed1i c\u00e1c v\u00f2ng, th\u00ed d\u1ee5 1,4-benzo\u0111iazepin (\u0111\u1ed3ng ph\u00e2n 3H) th\u00ec con s\u1ed1 tr\u01b0\u1edbc t\u00ean g\u1ecdi cho bi\u1ebft v\u1ecb tr\u00ed c\u1ee7a d\u1ecb t\u1eed \u0111\u1ed1i v\u1edbi v\u00f2ng benzen. Locant c\u1ee7a d\u1ecb t\u1eed l\u00fac n\u00e0y ph\u1ea3i b\u00e9 nh\u1ea5t. N\u00f3i chung, \u0111\u1ec3 thi\u1ebft l\u1eadp t\u00ean g\u1ecdi c\u1ee7a h\u1ec7 ng\u01b0ng t\u1ee5 c\u1ea7n x\u00e1c \u0111\u1ecbnh v\u00f2ng c\u01a1 s\u1edf v\u00e0 v\u1ecb tr\u00ed gh\u00e9p n\u1ed1i. V\u00f2ng c\u01a1 s\u1edf lu\u00f4n \u0111\u01b0\u1ee3c ch\u1ecdn l\u00e0 d\u1ecb v\u00f2ng ho\u1eb7c h\u1ec7 d\u1ecb v\u00f2ng ng\u01b0ng t\u1ee5, c\u00f3 t\u00ean g\u1ecdi th\u01b0\u1eddng. D\u00f9ng c\u00e1c ch\u1eef c\u00e1i a, b, c vi\u1ebft nghi\u00eang \u0111\u1ec3 k\u00fd hi\u1ec7u cho c\u00e1c c\u1ea1nh c\u1ee7a v\u00f2ng c\u01a1 s\u1edf. Ch\u1eef a gi\u1eefa c\u00e1c nguy\u00ean t\u1eed 1 v\u00e0 2 ; b : gi\u1eefa 2 v\u00e0 3 , th\u00ed d\u1ee5 : 3 Thiazol li----N L> 406","V\u1ecb tr\u00ed gh\u00e9p n\u1ed1i \u0111\u01b0\u1ee3c bi\u1ec3u di\u1ec5n b\u1eb1ng s\u1ed1, con s\u00f4' n\u00e0y \u0111\u1eb7t tr\u01b0\u1edbc ch\u1eef \u0111\u1eb7c tr\u01b0ng cho c\u1ea1nh c\u1ee7a v\u00f2ng c\u01a1 s\u1edf qua g\u1ea1ch n\u1ed1i. Tr\u1eadt t\u01b0 c\u1ee7a s\u1ed1 ph\u1ea3i t\u01b0\u01a1ng \u1ee9ng v\u1edbi tr\u1eadt t\u1ef1 c\u1ee7a ch\u1eef. S\u1ed1 v\u00e0 ch\u1eef \u0111\u01b0\u1ee3c \u0111\u1ec3 trong ngo\u1eb7c vu\u00f4ng v\u00e0 \u0111\u1eadt gi\u1eefa t\u00ean c\u1ea5u t\u1eed gh\u00e9p v\u00e0 t\u00ean v\u00f2ng c\u01a1 s\u1edf. T\u00ean c\u1ee7a c\u1ea5u t\u1eed gh\u00e9p c\u00f3 thay \u0111\u1ed5i m\u1ed9t \u00edt, th\u00ed d\u1ee5 : naphtalen -> naphto-, antraxen an tra-, furan -\u00bb furo-, thiophen \u2014> thieno-, pyri\u0111in \u2014> pyri\u0111o-, imi\u0111azol \u2014> imi\u0111axo-. Do \u0111\u00f3 locant trong ngo\u1eb7c vu\u00f4ng ch\u1ec9 t\u01b0\u01a1ng \u1ee9ng m\u1ed9t ph\u1ea7n ri\u00eang bi\u1ec7t c\u1ee7a h\u1ec7 ng\u01b0ng t\u1ee5. Th\u00ed d\u1ee5 d\u01b0\u1edbi \u0111\u00e2y m\u00f4 t\u1ea3 c\u00e1c c\u00e1ch gh\u00e9p n\u1ed1i v\u00f2ng thiazol v\u00e0 naphtalen. Thiazol ch\u1ec9 c\u00f3 th\u1ec3 gh\u00e9p n\u1ed1i \u1edf c\u1ea1nh d (v\u00ec v\u1edbi c\u00e1c c\u1ea1nh kh\u00e1c th\u00ec nguy\u00ean t\u1eed nit\u01a1 ho\u1eb7c l\u01b0u hu\u1ef3nh tr\u1edf th\u00e0nh m\u1ed9t ph\u1ea7n c\u1ee7a c\u1ea5u tr\u00fac naphtalen). Naphtalen c\u00f3 th\u1ec3 gh\u00e9p n\u1ed1i \u1edf c\u00e1c v\u1ecb tr\u00ed C\u1ecb - Cj ho\u1eb7c C2 - c 3, \u0111\u1ed3ng th\u1eddi c\u00e1c nguy\u00ean t\u1eed C| v\u00e0 c , kh\u00f4ng ph\u1ea3i l\u00e0 \u0111\u1ed3ng nh\u1ea5t. 1 v\u00e0 4n f Nb3 d\u1ecb O 2 oT\u1eeb r 1 a2 ta c\u00f3 Naphto[ 1,2-<\/]thiazol Naphto[2,3-d]thiazol Naphto[2,1-d]thiazol \u0110 \u00e1nh s\u00f4 h\u1ec7 ng\u01b0ng t\u1ee5. C\u00e1c \u0111i\u1ec1u ki\u1ec7n c\u1ea7n tu\u00e2n th\u1ee7 l\u00e0 : - d\u00e3y n\u1eb1m ngang c\u00f3 nhi\u1ec1u v\u00f2ng n h \u1ea5 t; - c\u00e1c v\u00f2ng c\u00f2n l\u1ea1i n\u1eb1m th\u1eb3ng g\u00f3c \u1edf ph\u00eda tr\u00ean ho\u1eb7c b\u00ean p h \u1ea3 i; - khi c\u00f3 d\u1ecb v\u00f2ng th\u00ec h\u1ec7 ph\u1ea3i \u0111\u01b0\u1ee3c \u0111\u1ecbnh h\u01b0\u1edbng sao cho d\u1ecb t\u1eed c\u00f3 locant nh\u1ecf nh\u1ea5t. Th\u00ed d\u1ee5 c\u1ea5u tr\u00fac ba v\u00f2ng (I) c\u00f3 th\u1ec3 bi\u1ec3u di\u1ec3n kh\u00f4ng ch\u1ec9 b\u1eb1ng c\u1eafc c\u00f4ng th\u1ee9c (II) - (IV) m\u00e0 c\u00f2n c\u00f3 nhi\u1ec1u c\u00e1ch kh\u00e1c n\u1eefa. Tuy v\u1eady, hai \u0111i\u1ec3m \u0111\u1ea7u c\u1ee7a c\u00e1c \u0111i\u1ec1u ki\u1ec7n c\u1ea7n tu\u00e2n th\u1ee7 ch\u1ec9 ph\u00f9 h\u1ee3p v\u1edbi c\u1ea5u tr\u00fac (I) v\u00e0 (II). Ti\u1ebfp theo, s\u1ef1 l\u1ef1a ch\u1ecdn ch\u1ec9 l\u00e0 c\u1ea5u tr\u00fac (I) v\u00ec \u1edf \u0111\u1eady nguy\u00ean t\u1eed nit\u01a1 \u1edf v\u1ecb tr\u00ed 4, c\u00f2n \u1edf c\u1ea5u tr\u00fac (II) l\u00e0 7, kh\u00f4ng ph\u00f9 h\u1ee3p. \u0111\u1ecbnh h\u01b0\u1edbng \u0111\u00fang \u0111\u1ecbnh h\u01b0\u1edbng kh\u00f4ng \u0111\u00fang 2 (I) (II) (III) (IV) Vi\u1ec7c \u0111\u00e1nh s\u1ed1 \u0111\u01b0\u1ee3c b\u1eaft \u0111\u1ea7u t\u1eeb v\u00f2ng b\u00ean ph\u1ea3i (ho\u1eb7c b\u00ean tr\u00ean) t\u1eeb nguy\u00ean t\u1eed th\u1ee9 nh\u1ea5t kh\u00f4ng tham gia v\u00e0o gh\u00e9p n\u1ed1i v\u1edbi c\u00e1c v\u00f2ng kh\u00e1c v\u00e0 theo chi\u1ec1u kim \u0111\u1ed3ng h\u1ed3. C\u00e1c nguy\u00ean t\u1eed cacbon \u1edf g\u00f3c kh\u00f4ng \u0111\u01b0\u1ee3c \u0111\u00e1nh s\u1ed1 m\u00e0 nh\u1eadn s\u1ed1 s\u1eb5n c\u00f3 c\u1ee7a nguy\u00ean t\u1eed tr\u01b0\u1edbc n\u00f3 c\u00f3 th\u00eam ch\u1eef a, b, c, ... Th\u00ed d\u1ee5 \u0111\u1ed1i v\u1edbi naphto[l,2-\u00ed\/]thiazol \u0111\u01b0\u1ee3c \u0111\u00e1hh s\u1ed1 nh\u01b0 sau : 407","\u0111\u1ecbnh h\u01b0\u1edbng v\u00e0 g\u1ecdi t\u00f4n \u0111\u00fang \u0111\u1ecbnh h\u01b0\u1edbng sai 2 t N = \u1ecb2 Ch\u1ecdn v\u00f2ng c\u01a1 s\u1edf. Trong tr\u01b0\u1eddng h\u1ee3p c\u00f3 th\u1ec3 t\u1ea1o nhi\u1ec1u t\u00ean g\u1ecdi c\u1ee7a h\u1ec7 ng\u01b0ng t\u1ee5 th\u00ec v\u00f2ng c\u01a1 s\u1edf \u0111\u01b0\u1ee3c ch\u1ecdn nh\u01b0 sau : 1. C\u1ea5u t\u1eed ch\u1ee9a nit\u01a1. Th\u00ed d\u1ee5 : Q XDN \\\" v\u00e0o 1 Furo[2,3-b]pyri\u0111in Trong th\u00ed d\u1ee5 tr\u00ean, khi \u0111\u00e1nh s\u1ed1 b\u1eaft \u0111\u1ea7u t\u1eeb d\u1ecb t\u1eed th\u00ec \u0111\u1ec3u nh\u1eadn \u0111\u01b0\u1ee3c locant c\u1ee7a c\u00e1c d\u1ecb t\u1eed l\u00e0 1 v\u00e0 7, nh\u01b0ng theo th\u1ee9 t\u1ef1 \u01b0u ti\u00ean th\u00ec ph\u1ea3i b\u1eaft \u0111\u1ea7u t\u1eeb oxi (O > s > N). 2. C\u1ea5u t\u1eed kh\u00f4ng ch\u1ee9a nit\u01a1 th\u00ec v\u00f2ng c\u01a1 s\u1edf \u0111\u01b0\u1ee3c ch\u1ecdn theo th\u1ee9 t\u1ef1 \u01b0u ti\u00ean : g: *ig J\u1ed5l Thieno[2,3-6]furan ch\u1ee9 kh\u00f4ng g\u1ecdi furo[2,3-6]thiophen 3. C\u1ea5u t\u1eed ch\u1ee9a nhi\u1ec1u v\u00f2ng. Trong th\u00ed d\u1ee5 d\u01b0\u1edbi \u0111\u00e2y, isoquinolin \u0111\u01b0\u1ee3c ch\u1ecdn ch\u1ee9 kh\u00f4ng ph\u1ea3i pyri\u0111in : v\u00e0 N 2 '3 6 54 Benzo[^]isoquinolin ch\u1ee9 kh\u00f4ng g\u1ecdi naphto[2,3-c]pyri\u0111in 4. C\u1ea5u t\u1eed ch\u1ee9a v\u00f2ng l\u1edbn h\u01a1n. Trong tr\u01b0\u1eddng h\u1ee3p n\u00e0y c\u1ea7n ch\u00fa \u00fd \u0111\u1ebfn c\u00e1ch \u0111\u00e1nh s\u1ed1 (c\u00e1c d\u1ecb t\u1eed ph\u1ea3i c\u00f3 locant b \u00e9 ): H 7H N1 N b v\u00e0 :g 4 N\u00ab Pyrolo[3,2-\u00f2]pyri\u0111in ch\u1ee9 kh\u00f4ng g\u1ecdi pyri\u0111o[3,2-\u00f2]pyrol 408","5. C\u1ea5u t\u1eed ch\u1ee9a nhi\u1ec1u d\u1ecb t\u1eed kh\u00e1c nhau. Th\u00ed d\u1ee5 : o \u1ed4\u1ed4;N ho\u1eb7c \u201eN o nTN H I H-PyrazoIo[4,5-6?]oxazol ch\u1ee9 kh\u00f4ng g\u1ecdi pyrazol[4,5-\u00ed\/]oxazol kh\u00f4ng g\u1ecdi lH-oxazolo[5.4-c]pyrazol 15.3.3 T\u00ean thay th\u00ea Ki\u1ec3u t\u00ean g\u1ecdi n\u00e0y c\u0169ng \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 t\u00ean g\u1ecdi \u201ca \u201d kh\u00f4ng ch\u1ec9 d\u00f9ng cho d\u1ecb v\u00f2ng m\u00e0 c\u00f2n d\u00f9ng cho c\u00e1c h\u1ee3p ch\u1ea5t kh\u00f4ng v\u00f2ng. Khi th\u1ebf c\u00e1c nh\u00f3m - CH2 - ho\u1eb7c - CH = trong c\u1ea5u tr\u00fac hi\u0111rocacbon b\u1eb1ng d\u1ecb t\u1eed th\u00ec t\u00ean g\u1ecdi \u0111\u01b0\u1ee3c th\u00eam ti\u1ec1n t\u1ed1 quen thu\u1ed9c oxa-, thia- ho\u1eb7c aza- \u0111\u1ed1i v\u1edbi oxi, l\u01b0u hu\u1ef3nh ho\u1eb7c nit\u01a1 t\u01b0\u01a1ng \u1ee9ng v\u00e0o t\u00ean hi\u0111rocacbon. Ti\u1ec1n t\u00f4' \u0111\u01b0\u1ee3c ghi nh\u1eadn theo th\u1ee9 t\u1ef1 \u0111\u1ed9 \u01b0u ti\u00ean v\u00e0 d\u1ecb t\u1eed \u0111\u01b0\u1ee3c \u0111\u00e1nh s\u00f4' v\u1edbi locant b\u00e9 nh\u1ea5t. V\u1edbi d\u00e3y kh\u00f4ng v\u00f2ng, t\u00ean g\u1ecdi n\u00e0y \u0111\u01b0\u1ee3c d\u00f9ng cho tr\u01b0\u1eddng h\u1ee3p khi g\u1ecdi t\u00ean nh\u00f3m th\u1ebf ph\u1ee9c t\u1ea1p, th\u00ed d\u1ee5 \u0111\u1ed1i v\u1edbi aminoete d\u01b0\u1edbi \u0111\u00e2y : 13 12 11 10 9 8 7 6 5 4 3 2 1 CH 3CH20CH2CH20 C H 2CH20 C H 2CH2NHCH3 5,8,1 l-Trioxa-2-azatri\u0111ecan V\u1edbi h\u1ec7 d\u1ecb v\u00f2ng ng\u01b0ng t\u1ee5 ch\u1ec9 c\u1ea7n bi\u1ebft t\u00ean g\u1ecdi hi\u0111rocacbon (v\u00f2ng ng\u01b0ng t\u1ee5 ho\u1eb7c c\u1ea7u n\u1ed1i) m\u00e0 kh\u00f4ng c\u1ea7n bi\u1ebft t\u00ean g\u1ecdi th\u01b0\u1eddng c\u1ee7a c\u1ea5u tr\u00fac d\u1ecb v\u00f2ng. C\u00e1ch \u0111\u00e1nh s\u1ed1 v\u1eabn gi\u1ed1ng nh\u01b0 \u0111\u1ed1i v\u1edbi hi\u0111rocacbon m\u00e0 kh\u00f4ng ph\u1ee5 thu\u1ed9c v\u1ecb tr\u00ed c\u1ee7a d\u1ecb t\u1eed. Th\u00ed d\u1ee5 : 8 07 1 9 .N n r\u00ec 2,7 -\u0110iazaphenantren C\u00d3 54 10 4 1,8,10-Triazaantraxen 1 -Oxa-4-thianaphtalen 4,7-\u0110iazaazulen \u1ee9t 7n L l-Azabixiclo[2.2. l]heptan w9 10 4 6-Oxaspiro[4.5]\u0111ecan Si \/O s^ X \/O . O' v o .2 1,4,8,11-Te\u01b0aoxaxiclotetra\u0111ecan Silaxiclopentan (Silolan) 409","15.4 T\u00ednh ch\u1ea5t \u1edf nhi\u1ec7t \u0111\u1ed9 ph\u00f2ng, c\u00e1c d\u1ecb v\u00f2ng no \u0111\u01a1n gi\u1ea3n \u0111\u1ec1u \u1edf th\u1ec3 l\u1ecfng (tr\u1eeb etilen o x it); ch\u00fang c\u00f3 nhi\u1ec7t \u0111\u1ed9 s\u00f4i cao h\u01a1n xicloankan t\u01b0\u01a1ng \u1ee9ng v\u00ec c\u00e1c d\u1ecb t\u1eed l\u00e0m t\u0103ng \u0111\u1ed9 ph\u00e2n c\u1ef1c c\u1ee7a ph\u00e2n t\u1eed. D\u01b0\u1edbi \u0111\u00e2y l\u00e0 nhi\u1ec7t \u0111\u1ed9 s\u00f4i c\u1ee7a m\u1ed9t s\u1ed1 d\u1ecb v\u00f2ng v\u00e0 xicloankan t\u01b0\u01a1ng \u1ee9ng : A 0 H Za -33\u00b0c ll\u00b0c sN ZA Z \u00c0 56\u00b0c 56\u00b0c \u25a1 D\u00b0 \u0169s d nh 12\u00b0c 48\u00b0c 94\u00b0C\/752 mmHg 63\u00b0C\/748 mmHg r1 r\u00b0\u00ec rH1 49\u00b0c 66\u00b0c 88\u00b0c thay nh\u00f3m - CH = CH - trong benzen b\u1eb1ng d\u1ecb t\u1eed, ta C\u00d3nhi\u1ec7t \u0111\u1ed9 s\u00f4i nh\u01b0 sau \u1ecc<3 \u1ecc o N H 80\u00b0c 32\u00b0c 84\u00b0c 131\u00b0c Nh\u01b0 v\u1eady, \u0111\u1ed1i v\u1edbi c\u00e1c h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng ch\u1ee9a nit\u01a1 c\u00f3 nh\u00f3m - NH - th\u00ec nhi\u1ec7t \u0111\u1ed9 s\u00f4i cao h\u01a1n, v\u00ec c\u00f3 li\u00ean k\u1ebft hi\u0111ro li\u00ean ph\u00e2n t\u1eed. M\u1eb7t kh\u00e1c, n\u1ebfu thay nh\u00f3m - CH = trong benzen b\u1eb1ng - N - th\u00ec nhi\u1ec7t \u0111\u1ed9 s\u00f4i t\u0103ng l\u00ean do \u0111\u1ed9 ph\u00e2n c\u1ef1c t\u0103ng, th\u00ed d\u1ee5 : 80\u00b0c 115\u00b0c 124\u00b0c 207\u00b0c |i = 2,26 D C\u00e1c d\u1ecb v\u00f2ng no c\u00f3 k\u00edch th\u01b0\u1edbc v\u00f2ng nh\u1ecf ( 3 - 4 c\u1ea1nh) d\u1ec5 tham gia ph\u1ea3n \u1ee9ng c\u1ed9ng m\u1edf v\u00f2ng v\u00e0 kh\u1ea3 n\u0103ng ph\u1ea3n \u1ee9ng cao h\u01a1n xicloankan v\u00f2ng nh\u1ecf nh\u1edd s\u1ef1 ph\u00e2n c\u1ef1c c\u1ee7a li\u00ean k\u1ebft cacbon - d\u1ecb t\u1eed. \/\u00b0 \\\\ +HBr ------------> CH2Br - CH2OH Ox\u1eeban |'~ y H + 2HC1 -------> C1CH2CH2CH2NH3+c f Azeti\u0111in 410","D\u00b0 v\u1ebft H2SO^ -> C2H5OCH2CH2CH2OH Oxietan + C2H5 0 H 25\u00b0c 3-Etoxipropan-l-ol H + 2HC1 (58%) N C6H5CHCH2NH3C r Q H ;-^ C1 2-Phenylaziri\u0111in 2-Clo-2-phenyletanamoni clorua SH H3C 0 + 100\u00b0c .C -C H o -N ) N H ,c h 3c H (61%) o H,0 C6H5CH2S - C H 2CH2CH2- O H j + C6H 5CH2S Na+ ^ (63%) 100 c N\u1ebfu d\u1ecb nguy\u00ean t\u1eed l\u00e0 nit\u01a1 m\u00e0 kh\u00f4ng li\u00ean h\u1ee3p v\u1edbi li\u00ean k\u1ebft 71, n\u00f3 s\u1ebd bi\u1ec3u hi\u1ec7n c\u00e1c t\u00ednh ch\u1ea5t c\u1ee7a m\u1ed9t amin nh\u01b0 t\u00ednh baz\u01a1 v\u00e0 ph\u1ea3n \u1ee9ng ankyl h\u00f3a. T\u00ednh baz\u01a1 c\u1ee7a d\u1ecb v\u00f2ng no ch\u1ee9a nit\u01a1 m\u1ea1nh h\u01a1n c\u1ee7a amin t\u01b0\u01a1ng \u1ee9ng, nh\u01b0ng t\u00ednh baz\u01a1 c\u1ee7a d\u1ecb v\u00f2ng th\u01a1m l\u1ea1i y\u1ebfu h\u01a1n. Th\u00ed d\u1ee5 : \u1eccH CH3 c h 3 Piperi\u0111in > I' I >o pK, 1 1 , 2 2 c h< 2 \/ c h 2 N r z Pyri\u0111in NH pKa 5,23 \u0110ietylamin pKa 10,93 C\u00e1c d\u1ecb v\u00f2ng thofm nh\u01b0 furan, thiophen, pyrol, pyri\u0111in tham gia c\u00e1c ph\u1ea3n \u1ee9ng th\u1ebf \u1edf nh\u00e2n th\u01a1m nh\u01b0 hi\u0111rocacbon th\u01a1m, nh\u01b0ng kh\u1ea3 n\u0103ng ph\u1ea3n \u1ee9ng s\u1ebd cao h\u01a1n hay th\u1ea5p h\u01a1n t\u00f9y theo c\u1ea5u tr\u00fac c\u1ee7a d\u1ecb v\u00f2ng v\u00e0 c\u01a1 ch\u1ebf ph\u1ea3n \u1ee9ng. D\u1eca V\u00d2NG TH\u01a0M S\u00c1U C\u1ea0NH 15.5 Nh\u00f3m pyri\u0111in Ch\u1ea5t \u0111\u1ea1i di\u1ec7n \u0111i\u1ec3n h\u00ecnh nh\u1ea5t c\u1ee7a d\u1ecb v\u00f2ng th\u01a1m s\u00e1u c\u1ea1nh m\u1ed9t d\u1ecb t\u1eed l\u00e0 pyri\u0111in. C\u00e1c d\u1eabn xu\u1ea5t c\u1ee7a pyri\u0111in c\u00f3 \u00fd ngh\u0129a sinh h\u1ecdc quan tr\u1ecdng, th\u00ed d\u1ee5 coenzym NAD+, NADP+ v\u00e0 c\u00e1c d\u1ea1ng kh\u1eed c\u1ee7a ch\u00fang, vitamin pp v\u00e0 c\u00e1c vitamin nh\u00f3m B6, m\u1ed9t s\u1ed1 ancaloit, ch\u1ea5t ph\u00f2ng tr\u1eeb d\u1ecbch h\u1ea1i v\u00e0 d\u01b0\u1ee3c ph\u1ea9m. 15.5.1 C\u1ea5u t\u1ea1o v\u00e0 \u0111\u1eb7c tr\u01b0ng chung c\u1ee7a kh\u1ea3 n\u0103ng ph\u1ea3n \u1ee9ng V\u1ec1 c\u1ea5u t\u1ea1o, n\u00f3 t\u01b0\u01a1ng t\u1ef1 benzen, ch\u1ec9 c\u00f3 m\u1ed9t m\u1eaft x\u00edch - CH = trong v\u00f2ng \u0111\u01b0\u1ee3c thay b\u1eb1ng - N =. Theo ph\u01b0\u01a1ng ph\u00e1p s\u01a1 \u0111\u1ed3 h\u00f3a tr\u1ecb, pyri\u0111in l\u00e0 s\u1ef1 lai h\u00f3a c\u1ed9ng h\u01b0\u1edfng c\u1ee7a m\u1ed9t v\u00e0i c\u1ea5u tr\u00fac gi\u1edbi h\u1ea1n gi\u1ed1ng nh\u01b0 benzen theo Kekule : 411","T\u1ea5t c\u1ea3 c\u00e1c nguy\u00ean t\u1eed cacbon v\u00e0 nguy\u00ean t\u1eed nit\u01a1 \u0111\u1ec1u c\u00f3 lai h\u00f3a sp2 v\u00e0 c\u00e1c li\u00ean k\u1ebft \u01a1 (C - c v\u00e0 c - N) n\u1eb1m tr\u00ean c\u00f9ng m\u1eb7t ph\u1eb3ng (h\u00ecnh 15.1). obitan p z th am gia li\u00ean h\u1ee3p \u1ee2) obitan sp 2 c\u00f3 c\u1eb7p ... w *\/ electron kh\u00f4ng ph\u00e2n chia _\/\/\/ ON<D \\\"0 a) H\u00ecnh 15.1 C\u1ea5u t\u1ea1o electron c\u1ee7a nguy\u00ean t\u1eed nit\u01a1 pyri\u0111in (a) v\u00e0 s\u1ef1 t\u1ea1o th\u00e0nh h\u1ec7 li\u00ean h\u1ee3p trong ph\u00e2n t\u1eed pyri\u0111in (b) \u1ede nguy\u00ean t\u1eed nit\u01a1 c\u00f3 3 obitan lai h\u00f3a th\u00ec 2 obitan t\u1ea1o li\u00ean k\u1ebft 0 v\u1edbi nguy\u00ean t\u1eed cacbon, c\u00f2n obitan th\u1ee9 ba ch\u1ee9a c\u1eb7p electron kh\u00f4ng ph\u00e2n chia, \u1edf obitan p kh\u00f4ng lai h\u00f3a n\u1ea7m th\u1eb3ng g\u00f3c v\u1edbi m\u1eb7t ph\u1eb3ng khung \u01a1 c\u00f3 1 electron, nh\u1edd electron n\u00e0y m\u00e0 nguy\u00ean t\u1eed nit\u01a1 tham gia t\u1ea1o th\u00e0nh \u0111\u00e1m m\u00e2y electron duy nh\u1ea5t v\u1edbi c\u00e1c obitan p c\u1ee7a 5 nguy\u00ean t\u1eed cacbon (x. h\u00ecnh 15.1b). Nguy\u00ean t\u1eed nit\u01a1 v\u1edbi c\u1ea5u h\u00ecnh electron nh\u01b0 th\u1ebf \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 nit\u01a1 pyri\u0111in. Nh\u01b0 v\u1eady, ph\u00e2n t\u1eed pyri\u0111in th\u1ecfa m\u00e3n v\u1edbi ti\u00eau chu\u1ea9n c\u1ee7a t\u00ednh th\u01a1m, \u0111\u00f3 l\u00e0 c\u00f3 m\u1eb7t ph\u1eb3ng khung \u01a1, h\u1ec7 electron li\u00ean h\u1ee3p \u0111\u00f3ng k\u00edn bao g\u1ed3m t\u1ea5t c\u1ea3 c\u00e1c nguy\u00ean t\u1eed c\u1ee7a v\u00f2ng v\u00e0 ch\u1ee9a 6 electron T\u00ed th\u1ecfa m\u00e3n c\u00f4ng th\u1ee9c Huckel (4n + 2 khi n = 1). Trong tr\u01b0\u1eddng h\u1ee3p n\u00e0y pyri\u0111in \u0111\u1eb3ng electron v\u1edbi benzen. Trong khi \u0111\u00f3 pyri\u0111in c\u00f3 m\u1ed9t s\u1ed1 c\u1ea5u tr\u00fac kh\u00e1c benzen. Th\u1ee9 nh\u1ea5t, ph\u00e2n t\u1eed c\u1ee7a n\u00f3 kh\u00f4ng ph\u1ea3i l\u00e0 h\u00ecnh 6 c\u1ea1nh \u0111\u1ec1u b\u1edfi v\u00ec li\u00ean k\u1ebft c - N ng\u1eafn h\u01a1n li\u00ean k\u1ebft c - c v\u00e0 do \u0111\u00f3 g\u00f3c h\u00f3a tr\u1ecb l\u1ec7ch 3 - 4\u00b0 so v\u1edbi 120\u00b0. Th\u1ee9 hai, pyri\u0111in c\u00f3 c\u1ef1c (2,26 D), \u0111\u00f3 l\u00e0 do nguy\u00ean t\u1eed nit\u01a1 c\u00f3 \u0111\u1ed9 \u00e2m \u0111i\u1ec7n l\u1edbn h\u01a1n so v\u1edbi cacbon, m\u1eb7t kh\u00e1c s\u1ef1 ph\u00e2n c\u1ef1c b\u1ed5 sung l\u00e0 do s\u1ef1 ph\u00e2n b\u1ed1 l\u1ea1i m\u1eadt \u0111\u1ed9 electron trong h\u1ec7 li\u00ean h\u1ee3p. B\u1eb1ng ch\u1ee9ng l\u00e0 s\u1ef1 so s\u00e1nh momen l\u01b0\u1ee1ng c\u1ef1c c\u1ee7a pyri\u0111in, \u0111\u1ed9 ph\u00e2n c\u1ef1c c\u1ee7a n\u00f3 l\u00e0 do hi\u1ec7u \u1ee9ng c\u1ea3m \u1ee9ng c\u1ee7a nguy\u00ean t\u1eed nit\u01a1. K\u1ebft qu\u1ea3 l\u00e0 trong ph\u00e2n t\u1eed pyri\u0111in ng\u01b0\u1eddi ta t\u00ecm th\u1ea5y s\u1ef1 ph\u00e2n b\u1ed1 m\u1eadt \u0111\u1ed9 electron kh\u00f4ng \u0111\u1ed3ng \u0111\u1ec1u. 0,139 nm 0,139 nm \u1ecb\u1ecbt V \u2022 \u1ecb ^ v \u2018\\\" 0,134 nm |i = 2,26 D n = 1,17 D P ip e ri\u0111 in Pyri\u0111in v\u00e0 c\u00e1c d\u1ecb v\u00f2ng kh\u00e1c ch\u1ee9a nguy\u00ean t\u1eed nit\u01a1 ki\u1ec3u pyri\u0111in (quinolin, c\u00e1c \u0111iazin) \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 h\u1ec7 khuy\u1ebft electron n hay thi\u1ebfu electron n. C\u00e1c h\u1ee3p ch\u1ea5t nh\u00f3m n\u00e0y v\u1ec1 h\u00ecnh th\u1ee9c \u0111\u01b0\u1ee3c coi l\u00e0 TC-t\u01b0\u01a1ng \u0111\u01b0\u01a1ng b\u1edfi v\u00ec s \u1ed1 electron 71 n\u00f3i chung t\u01b0\u01a1ng \u1ee9ng v\u1edbi s \u1ed1 nguy\u00ean t\u1eed trong","h\u1ec7 nhimg n\u00f3 v\u1eabn thu\u1ed9c v\u1ec1 7T-khuy\u1ebft l\u00e0 d\u1ef1a tr\u00ean t\u00ednh ch\u1ea5t nh\u1eadn electron c\u1ee7a d\u1ecb t\u1eed, d\u1eabn \u0111\u1ebfn khuy\u1ebft electron \u1edf c\u00e1c nguy\u00ean t\u1eed cacbon. T\u00ednh lu\u00e2n phi\u00ean c\u1ee7a \u0111i\u1ec7n t\u00edch ph\u1ea7n trong v\u00f2ng l\u00e0 t\u00ednh \u0111\u1eb7c bi\u1ec7t quan tr\u1ecdng c\u1ee7a s\u1ef1 ph\u00e2n b\u00f4' electron n trong pyri\u0111in : c\u00e1c nguy\u00ean t\u1eed c 2 v\u00e0 c 6 (v\u1ecb tr\u00ed a), c\u0169ng nh\u01b0 c 4 (v\u1ecb tr\u00ed y) c\u00f3 \u0111i\u1ec7n t\u00edch d\u01b0\u01a1ng ngh\u0129a l\u00e0 ch\u00fang thi\u1ebfu h\u1ee5t electron nhi\u1ec1u h\u01a1n, trong khi \u0111\u00f3 c\u00e1c nguy\u00ean t\u1eed c 3 v\u00e0 c 5 (v\u1ecb tr\u00ed \u1eca3) \u00e2m h\u01a1n m\u1ed9t \u00edt. S\u1ef1 t\u00ednh to\u00e1n c\u01a1 l\u01b0\u1ee3ng t\u1eed*}cho b\u1ee9c tranh \u0111\u1ecbnh l\u01b0\u1ee3ng \u0111i\u1ec7n t\u00edch n \u1edf m\u1ed7i m\u1ed9t nguy\u00ean t\u1eed c\u1ee7a v\u00f2ng trong ph\u00e2n t\u1eed pyri\u0111in : + 0,050 - 0,004 + 0,077 -0,195 M\u1ed9t trong c\u00e1c \u0111i\u1ec3m kh\u00e1c bi\u1ec7t c\u1ee7a pyri\u0111in so v\u1edbi benzen l\u00e0 t\u00ednh baz\u01a1 v\u1edbi s\u1ef1 t\u1ea1o th\u00e0nh mu\u1ed1i b\u1ec1n. Nguy\u00ean t\u1eed nit\u01a1 c\u1ee7a pyri\u0111in c\u00f3 kh\u1ea3 n\u0103ng t\u01b0\u01a1ng t\u00e1c v\u1edbi nhi\u1ec1u t\u00e1c nh\u00e2n electrophin, th\u1ec3 hi\u1ec7n t\u00ednh nucleophin c\u1ee7a n\u00f3 : C ) + E+ ------\u00bb [ f ^ | E+ = H+,R + (t\u1eeb R H al),N 0 2+, NN O H + (t\u1eeb R C O 3 H ), E RCO+ (t\u1eeb RCOHal), SO3 ... \u0110i\u1ec3m kh\u00e1c bi\u1ec7t n\u1eefa l\u00e0 ho\u1ea1t t\u00ednh th\u1ea5p c\u1ee7a pyri\u0111in v\u00e0 d\u1eabn xu\u1ea5t trong ph\u1ea3n \u1ee9ng th\u1ebf electrophin, nh\u01b0ng ho\u1ea1t t\u00ednh cao \u0111\u1ed1i v\u1edbi ph\u1ea3n \u1ee9ng th\u1ebf nucleophin. H\u01b0\u1edbng t\u1ea5n c\u00f4ng l\u00e0 do s\u1ef1 ph\u00e2n b\u1ed1 m\u1eadt \u0111\u1ed9 electron kh\u00f4ng \u0111\u1ed3ng \u0111\u1ec1u trong v\u00f2ng. T\u00e1c nh\u00e2n electrophin t\u1ea5n c\u00f4ng v\u00e0o v\u1ecb tr\u00ed p (nguy\u00ean t\u1eed c 3, c 5), t\u00e1c nh\u00e2n nucleophin v\u00e0o a v\u00e0 Y(nguy\u00ean t\u1eed C2, c 4, c 6) (s\u01a1 \u0111\u1ed3 15.1). Nu S\u01a1 \u0111 \u1ed5 15.1 V\u1ecb tr\u00ed c\u1ee7a s\u1ef1 t\u1ea5n c\u00f4ng electrophin (E) v\u00e0 nucleophin (Nu) trong ph\u1ea3n \u1ee9ng th\u1ebf \u1edf v\u00f2ng pyri\u0111in S\u1ef1 th\u1ebf electrophin v\u00e0o pyri\u0111in r\u1ea5t kh\u00f3 n\u00ean hi\u1ec7u su\u1ea5t s\u1ea3n ph\u1ea9m kh\u00f4ng cao. Ho\u1ea1t t\u00ednh th\u1ea5p c\u1ee7a pyri\u0111in l\u00e0 do thi\u1ebfu electron n c\u1ee7a d\u1ecb v\u00f2ng. Nhi\u1ec1u th\u00ed d\u1ee5 cho th\u1ea5y v\u00f2ng pyri\u0111in k\u00e9m ho\u1ea1t \u0111\u1ed9ng h\u01a1n benzen th\u1ebf kho\u1ea3ng 103 - 107 l\u1ea7n, ngh\u0129a l\u00e0 pyri\u0111in t\u01b0\u01a1ng t\u1ef1 nitrobenzen. M\u1ed9t nguy\u00ean nh\u00e2n kh\u00e1c l\u00e0 do trong m\u00f4i tr\u01b0\u1eddng axit, c\u00e2n b\u1eb1ng gi\u1eefa pyri\u0111in v\u00e0 mu\u1ed1i c\u1ee7a n\u00f3 th\u01b0\u1eddng chuy\u1ec3n d\u1ecbch v\u1ec1 ph\u00eda t\u1ea1o th\u00e0nh mu\u1ed1i, v\u00ec v\u1eady, n\u1ed3ng \u0111\u1ed9 c\u1ee7a baz\u01a1 - pyri\u0111in th\u1ea5p n\u00ean s\u1ef1 t\u1ea5n c\u00f4ng electrophin v\u00e0o nguy\u00ean t\u1eed cacbon c\u1ee7a v\u00f2ng (c\u00e1ch a) x\u1ea3y ra r\u1ea5t ch\u1eadm. \u0110i\u1ec1u ki\u1ec7n \u0111\u1ec3 t\u1ea5n c\u00f4ng electrophin v\u00e0o ion pyri\u0111ini (c\u00e1ch b) c\u0169ng kh\u00f4ng thu\u1eadn l\u1ee3i b\u1edfi v\u00ec s\u1ef1 t\u1ea1o th\u00e0nh ti\u1ec3u ph\u00e2n trung gian v\u1edbi hai \u0111i\u1ec7n t\u00edch d\u01b0\u01a1ng v\u1ec1 m\u1eb7t n\u0103ng l\u01b0\u1ee3ng l\u00e0 b\u1ea5t l\u1ee3 i: *\u2019 d\u1ef1a tr\u00ean plu\u00ed\u01a1ng ph\u00e1p obitan pli\u00e0n t\u1eed Hucke\u00ec 413","H+ (ho\u1eb7c E+), +^ NN H (a) (b) N H+ N+ N H Kh\u1ea3 n\u00e3ng ph\u1ea3n \u1ee9ng c\u1ee7a pyri\u0111in do s\u1ef1 proton h\u00f3a nguy\u00ean t\u1eed nit\u01a1 l\u00e0m gi\u1ea3m 10 3 l\u1ea7n, v\u00e0 trong to\u00e0n b\u1ed9 \u0111\u1ed1i v\u1edbi ph\u1ea3n \u1ee9ng th\u1ebf electrophin th\u00ec pyri\u0111in k\u00e9m benzen kho\u1ea3ng 1016- 1020 l\u1ea7n. S\u1ef1 c\u00f3 m\u1eb7t c\u1ee7a nguy\u00ean t\u1eed cacbon thi\u1ebfu h\u1ee5t electron \u1edf v\u1ecb tr\u00ed a v\u00e0 y trong pyri\u0111in l\u00e0m cho n\u00f3 c\u00f3 kh\u1ea3 n\u0103ng th\u1ebf nucleophin v\u00e0o nh\u00e2n. Tuy v\u1eady, vi\u1ec7c th\u1ebf nguy\u00ean t\u1eed hi\u0111ro trong pyri\u0111in t\u01b0\u01a1ng \u0111\u1ed1i kh\u00f3, nh\u01b0ng khi c\u00f3 c\u00e1c nh\u00f3m d\u1ec5 t\u00e1ch nh\u01b0 halogen ho\u1eb7c nitro \u1edf v\u1ecb tr\u00ed a ho\u1eb7c \u1ef4th\u00ec ph\u1ea3n \u1ee9ng th\u1ebf x\u1ea3y ra d\u1ec5 h\u01a1n. Th\u00ed d\u1ee5, t\u1ed1c \u0111\u1ed9 ph\u1ea3n \u1ee9ng th\u1ebf clo trong c\u00e1c d\u1eabn xu\u1ea5t clo h\u00f3a c\u1ee7a benzen v\u00e0 pyri\u0111in b\u1eb1ng ion metoxit t\u0103ng theo d\u00e3y : C1 C1 C1 N + +\u201e C1 N N C1 Ci H.3 CH; T\u1ed0C \u0111\u1ed9 t\u01b0\u01a1ng \u0111\u1ed1i 9.10 2.8.10 2,6.10 13 1,3.1021 c\u1ee7a ph\u1ea3n \u1ee9ng 15.5.2 T\u00ednh baz\u01a1 C\u1eb7p \u0111\u00f4i electron kh\u1ed5ng ph\u00e2n chia c\u1ee7a nguy\u00ean t\u1eed nit\u01a1 trong pyri\u0111in \u1edf obitan lai h\u00f3a sp2 kh\u00f4ng tham gia li\u00ean h\u01a1p, v\u00ec v\u1eady pyri\u0111in th\u1ec3 hi\u1ec7n t\u00ednh baz\u01a1, v\u1edbi axit m\u1ea1nh s\u1ebd t\u1ea1o th\u00e0nh mu\u1ed1i pyri\u0111ini k\u1ebft tinh : 4- HBr + Br N N H Pyri\u0111ini bromua Mu\u1ed1i pyri\u0111ini h\u1ea3o to\u00e0n t\u00ednh th\u01a1m b\u1edfi v\u00ec s\u1ef1 proton h\u00f3a \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n nh\u1edd c\u1eadp \u0111\u00f4i electron kh\u00f4ng ph\u00e2n chia, m\u00e0 c\u1eb7p \u0111\u00f4i electron n\u00e0y kh\u00f4ng tham gia t\u1ea1o khung th\u01a1m. T\u00ednh baz\u01a1 c\u1ee7a pyri\u0111in kh\u00f4ng cao (pKa = 5,2), k\u00e9m amoniac v\u00e0 amin th\u01a1m 4 - 6 b\u1eadc l\u00e0 do \u0111\u1ed9 \u00e2m \u0111i\u1ec7n c\u1ee7a nguy\u00ean t\u1eed nit\u01a1 lai h\u00f3a sp2 so v\u1edbi lai h\u00f3a sp3 c\u1ee7a nit\u01a1 trong amoniac (th\u00e0nh ph\u1ea7n s cao c\u1ee7a c\u1eb7p \u0111\u00f4i electron). V\u1edbi pyri\u0111in th\u1ebf th\u00ec nh\u00f3m th\u1ebf \u0111\u1ea9y electron l\u00e0m t\u0103ng t\u00ednh baz\u01a1, nh\u00f3m h\u00fat electron l\u00e0m gi\u1ea3m t\u00ednh baz\u01a1. Th\u00ed d\u1ee5 v\u1edbi c\u00e1c nh\u00f3m th\u1ebf \u1edf v\u1ecb tr\u00ed s\u1ed1 4 ta c\u00f3 c\u00e1c pKa l\u1ea7n l\u01b0\u1ee3t l\u00e0 : CH3 : 6,0 ; CH30 : 6,6 ; C1: 3,8 v\u00e0 N 0 2 : 1,9. 414","15.5.3 Ph\u00e1n \u1ee9ng v\u00f3i t\u00e1c nh\u00e2n electrophin Trong ph\u00e2n t\u1eed pvri\u0111in c\u00f3 hai trung t\u00e2m ph\u1ea3n \u1ee9ng c\u00f3 kh\u1ea3 n\u0103ng ti\u1ebfp nh\u1eadn s\u1ef1 t\u1ea5n c\u1ed1ng electrophin : - nguy\u00ean t\u1eed nit\u01a1 v\u1edbi c\u1eb7p electron kh\u00f4ng ph\u00e2n chia ; - h\u1ec7 electron 71c\u1ee7a v\u00f2ng th\u01a1m. a) C\u1ed9ng v\u00e0o nguy\u00ean t\u1eed nit\u01a1 Ngo\u00e0i proton, nguy\u00ean t\u1eed nit\u01a1 c\u00f3 th\u1ec3 c\u1ed9ng c\u00e1c ti\u1ec3u ph\u00e2n electrophin kh\u00e1c \u0111\u1ec3 chuy\u1ec3n th\u00e0nh cation pyri\u0111ini. A nkyl h\u00f3a. Khi t\u01b0\u01a1ng t\u00e1c v\u1edbi t\u00e1c nh\u00e2n ankyl h\u00f3a nh\u01b0 ankyl halogenua ho\u1eb7c ankyl sun\u00edat th\u00ec nguy\u00ean t\u1eed nit\u01a1 th\u1ec3 hi\u1ec7n t\u00ednh nucleophin v\u00e0 t\u1ea1o li\u00ean k\u1ebft c\u1ed9ng h\u00f3a tr\u1ecb v\u1edbi nguy\u00ean t\u1eed electrophin l\u00e0 cacbon c\u1ee7a t\u00e1c nh\u00e2n ph\u1ea3n \u1ee9ng. Mu\u1ed1i N-ankylpyri\u0111ini l\u00fac n\u00e0y v\u1eabn gi\u1eef nguy\u00ean t\u00ednh th\u01a1m b\u1edfi v\u00ec sau ph\u1ea3n \u1ee9ng 6 electron th\u01a1m kh\u00f4ng b\u1ecb ph\u00e1 v\u1ee1 : I CH3 N-metyl pyri\u0111ini io\u0111ua Kh\u00e1c v\u1edbi s\u1ef1 proton h\u00f3a, vi\u1ec7c ankyl h\u00f3a nguy\u00ean t\u1eed nit\u01a1 r\u1ea5t nh\u1ea1y c\u1ea3m v\u1edbi \u00e1n ng\u1eef kh\u00f4ng gian. T\u1ea5t c\u1ea3 c\u00e1c nh\u00f3m th\u1ebf \u1edf v\u1ecb tr\u00ed 2, k\u1ec3 c\u1ea3 nh\u00f3m \u0111\u1ea9y electron \u0111\u1ec1u l\u00e0m cho ph\u1ea3n \u1ee9ng x\u1ea3y ra kh\u00f3 kh\u00e3n; nh\u1eefng h\u1ee3p ch\u1ea5t nh\u01b0 th\u1ebf b\u1ecb ankyl h\u00f3a kh\u00f3 hom pyri\u0111in. Th\u00ed d\u1ee5, nh\u00f3m metyl l\u00e0m gi\u1ea3m t\u1ed1c \u0111\u1ed9 ph\u1ea3n \u1ee9ng 6,5 l\u1ea7n ; nh\u00f3m isopropyl gi\u1ea3m t\u1ed1c \u0111\u1ed9 75 l\u1ea7n ; 2,6-\u0111im etyl pyri\u0111in ph\u1ea3n \u1ee9ng ch\u1eadm h\u01a1n 40 l\u1ea7n ; c\u00f2n 2-te\/7-butyl pyri\u0111in h\u1ea7u nh\u01b0 kh\u00f4ng b\u1ecb ankyl h\u00f3a \u1edf 60\u00b0c. A xyl h\u00f3a. Khi t\u01b0\u01a1ng t\u00e1c v\u1edbi anhi\u0111rit ho\u1eb7c halogenanhi\u0111rit c\u1ee7a axit cacboxylic th\u00ec d\u1ec5 d\u00e0ng nh\u1eadn \u0111\u01b0\u1ee3c mu\u1ed1i N-axylpyri\u0111ini v\u1edbi hi\u1ec7u su\u1ea5t t\u1ed1t (mu\u1ed1i b\u1ecb th\u1ee7y ph\u00e2n \u1edf kh\u00f4ng kh\u00ed \u1ea9m) : N-axylpyri\u0111ini clorua Mu\u1ed1i N-axylpyri\u0111ini d\u1ec5 b\u1ecb t\u1ea5n c\u00f4ng nucleophin v\u00e0o nguy\u00ean t\u1eed cacbon c\u1ee7a nh\u00f3m cacbonyl, v\u00ec v\u1eady ng\u01b0\u1eddi ta d\u00f9ng ph\u1ea3n \u1ee9ng n\u00e0y l\u00e0m t\u00e1c nh\u00e2n axyl h\u00f3a. Vi\u1ec7c axyl h\u00f3a \u0111\u01b0\u1ee3c ti\u1ebfn h\u00e0nh khi d\u01b0 pyri\u0111in m\u00e0 kh\u00f4ng c\u1ea7n t\u00e1ch ra mu\u1ed1i axylpyri\u0111ini, sau \u0111\u00f3 x\u1eed l\u00fd mu\u1ed1i n\u00e0y v\u1edbi ancol ho\u1eb7c amin, th\u00ed d\u1ee5 : 20- HHCT2 415","+ , C1 + ROH py -> CH3- C ^ + \u1ecb + I C1 N OR N I H c. 'C H 3 Ph\u01b0\u01a1ng ph\u00e1p n\u00e0y r\u1ea5t t\u1ed1t khi axyl h\u00f3a h\u1ee3p ch\u1ea5t \u00edt b\u1ec3n trong m\u00f4i tr\u01b0\u1eddng axit. Sunfo h\u00f3a. Pyri\u0111in ph\u1ea3n \u1ee9ng m\u1ea1nh v\u1edbi l\u01b0u hu\u1ef3nh trioxit t\u1ea1o th\u00e0nh pyri\u0111ini-l-sunfonat tinh th\u1ec3, \u0111\u01b0\u1ee3c bi\u1ebft d\u01b0\u1edbi t\u00ean g\u1ecdi pyri\u0111in sunfotrioxit. N\u00f3 l\u00e0 h\u1ee3p ch\u1ea5t c\u00f3 kh\u1ea3 n\u00e3ng ph\u1ea3n \u1ee9ng m\u1ea1nh, b\u1ecb th\u1ee7y ph\u00e2n b\u1eb1ng n\u01b0\u1edbc n\u00f3ng : . * \u00bb1 ^ 0 Q ) hso; N N N H () = s =0 1 Pyri\u0111ini hi\u0111rosun\u0129at 0 Pyri\u0111in sun\u00edotrioxit (90%) Pyri\u0111in sunfotrioxit ch\u1ee7 y\u1ebfu \u0111\u01b0\u1ee3c d\u00f9ng l\u00e0m t\u00e1c nh\u00e2n sunfo h\u00f3a \u00eam d\u1ecbu cho c\u00e1c h\u1ee3p ch\u1ea5t d\u1ecb v\u00f2ng k\u1ef5 axit. Nitro h\u00f3a. Nitro h\u00f3a v\u00e0o nguy\u00ean t\u1eed nit\u01a1 \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n d\u1ec5 d\u00e0ng khi t\u00e1c d\u1ee5ng v\u1edbi nit\u01a1 (V) oxit ho\u1eb7c mu\u1ed1i nitroni, th\u00ed d\u1ee5 bo\u00edlonitroni NO^Bpy. D\u1eabn xu\u1ea5t N-nitroni t\u1ea1o th\u00e0nh \u0111\u01b0\u1ee3c d\u00f9ng l\u00e0m t\u00e1c nh\u00e2n nitro h\u00f3a \u00eam d\u1ecbu kh\u00f4ng c\u00f3 \u0111\u1eb7c tr\u01b0ng axit nh\u01b0 khi nitro h\u00f3a benzen d\u01b0\u1edbi \u0111\u00e2y : 4- n o 2+b f 4- ^ Q b f 4- SL\u1eca\u1ead. Q 2 + Q b f 4- N N^ N H L no2 1-Nitropyri\u0111ini bo florua Khi cho axit nitric t\u00e1c d\u1ee5ng tr\u1ef1c ti\u1ebfp l\u00ean pyri\u0111in ch\u1ec9 nh\u1eadn \u0111\u01b0\u1ee3c N-proton h\u00f3a, ngh\u0129a l\u00e0 t\u1ea1o th\u00e0nh mu\u1ed1i pyri\u0111ini. b) Th\u00ea v\u00e0o nguy\u00ean t\u1eed cacbon M\u1eb7c d\u00f9 t\u00e1c nh\u00e3n electrophin tr\u01b0\u1edbc h\u1ebft t\u1ea5n c\u00f4ng v\u00e0o nguy\u00ean t\u1eed nit\u01a1 nucleophinic, nh\u01b0ng ph\u1ea3n \u1ee9ng nh\u01b0 th\u1ebf th\u01b0\u1eddng l\u00e0 thu\u1eadn ngh\u1ecbch v\u00e0 trong m\u00f4i tr\u01b0\u1eddng axit t\u1ed3n t\u1ea1i m\u1ed9t l\u01b0\u1ee3ng nh\u1ecf baz\u01a1 t\u1ef1 do. VI v\u1eady, ph\u1ea3n \u1ee9ng th\u1ebf electrophin trong d\u00e3y pyri\u0111in c\u0169ng c\u00f3 th\u1ec3 x\u1ea3y ra nh\u01b0ng ti\u1ebfn h\u00e0nh trong \u0111i\u1ec1u ki\u1ec7n kh\u1eafc nghi\u1ec7t v\u00e0 r\u1ea5t kh\u00f3 kh\u0103n, k\u1ec3 c\u1ea3 nh\u1eefng ph\u1ea3n \u1ee9ng th\u00f4ng th\u01b0\u1eddng c\u0169ng kh\u00f4ng x\u1ea3y ra v\u1edbi pyridin (th\u00ed d\u1ee5 ph\u1ea3n \u1ee9ng ankyl h\u00f3a v\u00e0 axyl h\u00f3a theo Fri\u0111en - Crap). C\u01a1 ch\u1ebf ph\u1ea3n \u1ee9ng ph\u1ea7n l\u1edbn gi\u1ed1ng v\u1edbi ph\u1ea3n \u1ee9ng th\u1ebf electrophin trong aren. S\u1ef1 l\u1ea5n c\u00f4ng c\u1ee7a t\u00e1c nh\u00e2n electrophin v\u00e0o v\u1ecb tr\u00ed (3 \u0111\u01b0\u1ee3c gi\u1ea3i th\u00edch kh\u00f4ng ch\u1ec9 b\u1eb1ng s\u1ef1 ph\u00e2n b\u00f4 m\u1eadt \u0111\u1ed9 clcctron \u1edf tr\u1ea1ng th\u00e1i t\u0129nh m\u00e0 c\u00f2n do t\u00ednh b\u1ec1n l\u1edbn c\u1ee7a ph\u1ee9c \u01a1 t\u1ea1o th\u00e0nh khi t\u1ea5n c\u00f4ng v\u00e0o p. 416","Khi t\u1ea5n c\u00f4ng v\u1ecb tr\u00ed cx (c\u0169ng nh\u01b0 y) m\u1ed9t trong c\u00e1c c\u1ea5u t\u1ea1o gi\u1edbi h\u1ea1n c\u1ee7a ph\u1ee9c \u01a1 gi\u1ea3 thi\u1ebft l\u00e0 \u0111\u1ecbnh x \u1ee9 \u0111i\u1ec7n t\u00edch d\u01b0\u01a1ng \u1edf nguy\u00ean t\u1eed \u00e2m \u0111i\u1ec7n nit\u01a1, kh\u00f4ng thu\u1eadn l\u1ee3i v\u1ec1 m\u1eadt n\u0103ng l\u01b0\u1ee3ng v\u00e0 kh\u00f4ng t\u1ea1o th\u00e0nh s\u1ea3n ph\u1ea9m th\u1ebf \u1edf a. t\u1ea5n c\u00f4ng p E E H H -H ' N N NN N E E E NH t\u1ea5n c\u00f4ng a H ph\u1ee9c \u01a1 NH c\u1ea5u t\u1ea1o kh\u00f4ng thu\u1eadn l\u1ee3i Nitro h\u00f3a. Pyri\u0111in b\u1ecb nitro h\u00f3a v\u00e0o nh\u00e2n \u1edf \u0111i\u1ec1u ki\u1ec7n kh\u1eafc nghi\u1ec7t. Ph\u01b0\u01a1ng \u00e1n c\u1ed5 \u0111i\u1ec3n ti\u1ebfn h\u00e0nh ph\u1ea3n \u1ee9ng khi d\u00f9ng h\u1ed7n h\u1ee3p nitro h\u00f3a s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c kh\u00f4ng qu\u00e1 6% 3-nitropyri\u0111in*' \u1edf 300\u00b0c. N\u1ebfu thay axit nitric b\u1eb1ng kali nitrat th\u00ec k\u1ebft qu\u1ea3 s\u1ebd t\u1ed1t h\u01a1n : k n o 3, h 2s o 4 \u0111 NO, N' 300\u201dc N (15%) Khi c\u00f3 m\u1eb7t nh\u00f3m th\u1ebf ankyl th\u00ec qu\u00e1 tr\u00ecnh nitro h\u00f3a d\u1ec5 h\u01a1n, nh\u01b0ng trong nh\u00e2n ph\u1ea3i c\u00f3 t\u1ed1i thi\u1ec3u hai nh\u00f3m th\u1ebf \u0111\u1ec3 cho vi\u1ec7c oxi h\u00f3a nh\u00f3m th\u1ebf kh\u00f4ng c\u1ea1nh tranh v\u1edbi ph\u1ea3n \u1ee9ng nitro h\u00f3a. Th\u00ed d\u1ee5, coli\u0111in \u0111\u1ed1i x\u1ee9ng b\u1ecb nitro h\u00f3a v\u1edbi hi\u1ec7u su\u1ea5t cao \u1edf \u0111i\u1ec1u ki\u1ec7n \u00eam d\u1ecbu h\u01a1n nhi\u1ec1u : CH3 ch HNO3 (1, oleum H ,c 100\u00b0 c h 3c n c h 3 2,4,6-trimetyl-3-nitropyri\u0111in (90%) Sunfo h\u00f3a. Pyri\u0111in r\u1ea5t tr\u01a1 v\u1edbi t\u00e1c d\u1ee5ng c\u1ee7a axit sun\u00eduric \u0111\u1eb7c v\u00e0 oleum. Khi \u0111un n\u00f3ng l\u00e2u \u1edf nhi\u1ec7t \u0111\u1ed9 320\u00b0c ch\u1ec9 t\u1ea1o th\u00e0nh axit pyri\u0111in-3-sunfonic v\u1edbi hi\u1ec7u su\u1ea5t r\u1ea5t th\u1ea5p. S\u1ef1 sunfo h\u00f3a x\u1ea3y ra d\u1ec5 h\u01a1n khi c\u00f3 m\u1eb7t ch\u1ea5t x\u00fac t\u00e1c l\u00e0 mu\u1ed1i th\u1ee7y ng\u00e2n (II) ho\u1eb7c nh\u00f4m clorua. Vai tr\u00f2 c\u1ee7a x\u00fac t\u00e1c v\u1eabn ch\u01b0a \u0111\u01b0\u1ee3c l\u00e0m r\u00f5. + h 2s o 4 \u0111\u0103c SO3 H N 220\u00b0c N (70%) ; Tromg t\u1ea5t c\u1ea3 c\u00e1c ph\u1ea3n \u1ee9ng ti\u1ebfn h\u00e0nh \u1ecf m\u00f4i tr\u01b0\u1eddng axit m\u1ea1nh, s\u1ea3n ph\u1ea9m \u0111\u01b0\u1ee3c t\u1ea1o th\u00e0nh \u1edf d\u1ea1ng mu\u1ed1i. V\u00ec mu\u1ed1i d \u1ec5 d\u00e0ng chuy\u1ec3n th\u00e0nh baz\u01a1 t\u1ef1 do b\u1eb1ng t\u00e1c d\u1ee5ng c\u1eeda ki\u1ec1m n\u00ean giai \u0111o\u1ea1n n\u00e0y \u1edf \u0111\u00e2y v\u00e0 c\u00e1c s\u01a1 \u0111\u1ed3 sau \u0111\u01b0\u1ee3c b \u1ecf qua. 417","Halogen h\u00f3a. Brom h\u00f3a pyri\u0111in \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n th\u00e0nh c\u00f4ng khi c\u00f3 m\u1eb7t oleum. C\u00f3 th\u1ec3 ph\u00e1n \u1ee9ng x\u1ea3y ra qua s\u1ef1 t\u1ea1o th\u00e0nh pyri\u0111in sun\u00edotrioxil, b\u1edfi v\u00ec n\u1ebfu ch\u1ec9 c\u00f3 H2S 0 4 95% th\u00ec ph\u1ea3n \u1ee9ng kh\u00f4ng x\u1ea3y ra. ( 86%) Ti\u1ebfn h\u00e0nh clo h\u00f3a pyri\u0111in khi c\u00f3 m\u1eb7t nh\u00f4m clorua \u1edf 100\u00b0c s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c 3-clopyri\u0111in v\u1edbi hi\u1ec7u su\u1ea5t kh\u00f4ng cao (33%). 15.5.4 Ph\u1ea3n \u1ee9ng v\u1edbi t\u00e1c nh\u00e2n nucleophin Kh\u00e1c v\u1edbi c\u00e1c h\u1ee3p ch\u1ea5t c\u1ee7a d\u00e3y benzen, pyri\u0111in v\u00e0 d\u1eabn xu\u1ea5t c\u00f3 th\u1ec3 tham gia ph\u1ea3n \u1ee9ng th\u1ebf nucleophin v\u00e0o nh\u00e2n th\u01a1m. Ph\u1ea3n \u1ee9ng c\u00f3 th\u1ec3 x\u1ea3y ra nh\u01b0 sau : 6* Trong \u0111i\u1ec1u ki\u1ec7n t\u01b0\u01a1ng t\u1ef1 nhau v\u1ec1 c\u01a1 ch\u1ebf th\u1ebf eiectrophin v\u00e0 nucleophin c\u1ee7a lii\u0111ro trong h\u1ec7 th\u01a1m c\u1ea7n ph\u1ea3i ghi nh\u1eadn s\u1ef1 kh\u00e1c nhau v\u1ec1 nguy\u00ean t\u1eafc trong ph\u1ea3n \u1ee9ng n\u00e0y. \u1eda s\u1ef1 th\u1ebf electrophin, hi\u0111ro b\u1ecb t\u00e1ch ra \u1edf giai \u0111o\u1ea1n cu\u1ed1i d\u01b0\u1edbi d\u1ea1ng proton kh\u00e1 d\u1ec5 th\u00ec \u1edf s\u1ef1 th\u1ebf nucleophin ph\u1ea3n \u1ee9ng \u0111\u01b0\u1ee3c k\u1ebft th\u00fac b\u1eb1ng c\u00e1ch lo\u1ea1i ion hi\u0111rua. Giai \u0111o\u1ea1n n\u00e0y x\u1ea3y ra kh\u00f3 v\u00e0 th\u01b0\u1eddng \u0111\u00f2i h\u1ecfi s\u1ef1 c\u00f3 m\u1eb7t c\u1ee7a ch\u1ea5t oxi h\u00f3a \u0111\u00f3ng vai tr\u00f2 l\u00e0 ch\u1ea5t nh\u1eadn ion hi\u0111rua. Thu\u1ed9c lo\u1ea1i ph\u1ea3n \u1ee9ng th\u1ebf nucleophin l\u00e0 ph\u1ea3n \u1ee9ng amin h\u00f3a, hi\u0111roxyl h\u00f3a v\u00e0 ankyl h\u00f3a (aryl h\u00f3a), ngh\u0129a l\u00e0 \u0111\u01b0a tr\u1ef1c ti\u1ebfp nh\u00f3m nucleophin v\u00e0o v\u00f2ng pyri\u0111in v\u00e0 \u0111\u1ed3ng \u0111\u1eb3ng c\u1ee7a n\u00f3. \u0110\u1ed1i v\u1edbi d\u1eabn xu\u1ea5t c\u1ee7a pyri\u0111in c\u0169ng c\u00f3 th\u1ec3 th\u1ebf khi nh\u00e2n \u0111\u00e3 c\u00f3 nh\u00f3m ch\u1ee9c t\u01b0\u01a1ng t\u1ef1 nh\u01b0 trong d\u00e3y benzen. A m in h\u00f3a. Vi\u1ec7c \u0111\u01b0a tr\u1ef1c ti\u1ebfp nh\u00f3m amino v\u00e0o nh\u00e3n pyri\u0111in \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 ph\u1ea3n \u1ee9ng Chichibabin (1914) l\u00e0 th\u00ed d\u1ee5 \u0111i\u1ec3n h\u00ecnh nh\u1ea5t c\u1ee7a s\u1ef1 th\u1ebf nucleophin. Ph\u1ea3n \u1ee9ng th\u01b0\u1eddng x\u1ea3y ra khi \u0111un pyri\u0111in v\u1edbi natri ami\u0111ua ho\u1eb7c kali ami\u0111ua trong dung m\u00f4i aproton kh\u00f4ng n\u01b0\u1edbc (hi\u0111rocacbon ho\u1eb7c N,N-\u0111imetylanilin). C\u00f3 th\u1ec3 ti\u1ebfn h\u00e0nh ph\u1ea3n \u1ee9ng trong m\u00f4i tr\u01b0\u1eddng amoniac l\u1ecfng \u1edf nhi\u1ec7t \u0111\u1ed9 ph\u00f2ng v\u00e0 c\u0169ng c\u00f3 th\u1ec3 \u1edf - 33\u00b0c (nhi\u1ec7t \u0111\u1ed9 s\u00f4i c\u1ee7a amoniac) nh\u01b0ng l\u00fac n\u00e0y t\u1ed1c \u0111\u1ed9 ph\u1ea3n \u1ee9ng r\u1ea5t th\u1ea5p. Trong c\u1ea3 hai tr\u01b0\u1eddng h\u1ee3p \u0111\u1ec1u t\u1ea5n c\u00f4ng v\u00e0o v\u1ecb tr\u00ed a , c\u00f2n khi m\u00e0 c\u1ea3 hai v\u1ecb tr\u00ed a b\u1ecb chi\u1ebfm th\u00ec s\u1ebd t\u1ea1o th\u00e0nh \u0111\u1ed3ng ph\u00e2n y nh\u01b0ng hi\u1ec7u su\u1ea5t th\u1ea5p : NaOH (75%) Khi c\u00f3 d\u01b0 ami\u0111ua kim lo\u1ea1i \u1edb nhi\u1ec7t \u0111\u1ed9 cao (160 - 180\u00b0C) s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c 2,6-\u0111iamino- pyri\u0111in v\u1edbi hi\u1ec7u su\u1ea5t cao. 418","Ph\u1ea3n \u1ee9ng amin h\u00f3a \u0111\u01b0\u1ee3c d\u00f9ng r\u1ed9ng r\u00e3i v\u00ec t\u1eeb aminopyri\u0111in c\u00f3 th\u1ec3 d\u1ec5 d\u00e0ng \u0111i\u1ec1u ch\u1ebf c\u00e1c d\u1eabn xu\u1ea5t kh\u00e1c nhau c\u1ee7a pyri\u0111in. C\u01a1 ch\u1ebf c\u1ee7a ph\u1ea3n \u1ee9ng Chichibabin : M\u1eb7c d\u00f9 c\u01a1 ch\u1ebf \u0111\u1ea7u ti\u00ean \u0111\u01b0a ra t\u1eeb n\u0103m 1930, nh\u01b0ng \u0111\u1ebfn nay t\u1ea5t c\u1ea3 c\u00e1c chi ti\u1ebft c\u1ee7a c\u01a1 ch\u1ebf v\u1eabn ch\u01b0a \u0111\u01b0\u1ee3c gi\u1ea3i quy\u1ebft \u0111\u1ebfn t\u1eadn c\u00f9ng. \u0110i\u1ec1u \u0111\u00f3 l\u00e0 do ph\u1ea3n \u1ee9ng l\u00e0 qu\u00e1 tr\u00ecnh d\u1ecb th\u1ec3, natri ami\u0111ua th\u1ef1c t\u1ebf kh\u00f4ng tan trong dung m\u00f4i \u0111em d\u00f9ng. V\u1ec1 c\u00e1c d\u1ea5u hi\u1ec7u th\u00f4ng th\u01b0\u1eddng, ph\u1ea3n \u1ee9ng thu\u1ed9c lo\u1ea1i th\u1ebf nucleophin v\u00e0o nh\u00e2n th\u01a1m (SNAr) c\u1ee7a ion hi\u0111rua b\u1eb1ng ion ami\u0111ua N H ,. N\u1ebfu nghi\u00eam ng\u1eb7t h\u01a1n th\u00ec c\u00f3 th\u1ec3 xem l\u00e0 ph\u1ea3n \u1ee9ng c\u1ed9ng - t\u00e1ch (c\u01a1 ch\u1ebf AE). Th\u1ef1c ra, \u1edf giai \u0111o\u1ea1n \u0111\u1ea7u ti\u00ean ion ami\u0111ua t\u1ea5n c\u00f4ng v\u00e0o nguy\u00ean t\u1eed c 2 thi\u1ebfu electron \u0111\u1ec3 t\u1ea1o th\u00e0nh ph\u1ee9c \u01a1 amin (nguy\u00ean nh\u00e2n c\u1ee7a s\u1ef1 ch\u1ecdn l\u1ecdc cao v\u00e0o C2 ch\u1ee9 kh\u00f4ng v\u00e0o c 4 \u0111\u1ebfn nay v\u1eabn ch\u01b0a \u0111\u01b0\u1ee3c gi\u1ea3i th\u00edch r \u00f5 ) : + NaNH2 ------> H N' N\u2019 'N H 2 'N ' ' NH Na+ Na+ s\u1ea3n ph\u1ea9m ch\u01b0a x\u1eed l\u00fd ph\u1ee9c G , h2 N NH Na _ _ _ J. rN - n X I\\\\\u2014 Na tr\u1ea1ng th\u00e1i chuy\u1ebfn ti\u1ebfp Giai \u0111o\u1ea1n ch\u00eca kh\u00f3a c\u1ee7a ph\u1ea3n \u1ee9ng l\u00e0 s\u1ef1 th\u01a1m h\u00f3a ph\u1ee9c \u01a1. Trong tr\u01b0\u1eddng h\u1ee3p ph\u1ea3n \u1ee9ng ti\u1ebfn h\u00e0nh khi \u0111un n\u00f3ng, ion hi\u0111rua t\u1ef1 t\u00e1ch kh\u1ecfi ph\u1ee9c \u01a1 d\u01b0\u1edbi d\u1ea1ng ph\u00e2n t\u1eed H2 (nguy\u00ean t\u1eed hi\u0111ro th\u1ee9 hai t\u00e1ch ra d\u01b0\u1edbi d\u1ea1ng proton t\u1eeb aminopyri\u0111in). Giai \u0111o\u1ea1n quan tr\u1ecdng n\u00e0y ch\u1ee9ng t\u1ecf v\u1ec1 \u0111\u1eb7c tr\u01b0ng t\u1ef1 x\u00fac t\u00e1c c\u1ee7a ph\u1ea3n \u1ee9ng, ngh\u0129a l\u00e0 m\u1ed9t trong c\u00e1c s\u1ea3n ph\u1ea9m t\u1ea1o th\u00e0nh, m\u00e0 ch\u00ednh l\u00e0 mu\u1ed1i natri c\u1ee7a 2-aminopyri\u0111in th\u00fac \u0111\u1ea9y s\u1ef1 t\u00e1ch ion hi\u0111rua. Gi\u1ea3 thi\u1ebft r\u1eb1ng s\u1ef1 t\u00e1ch x\u1ea3y ra qua tr\u1ea1ng th\u00e1i chuy\u1ec3n ti\u1ebfp v\u00f2ng. Hi\u0111roxyl h\u00f3a. Pyri\u0111in c\u00f3 khuynh h\u01b0\u1edbng tham gia m\u1ed9t ph\u1ea3n \u1ee9ng n\u1eefa m\u00e0 benzen kh\u00f4ng c\u00f3 - \u0111\u00f3 l\u00e0 \u0111\u01b0a tr\u1ef1c ti\u1ebfp nh\u00f3m hi\u0111roxyl v\u00e0o nh\u00e2n. Ph\u1ea3n \u1ee9ng x\u1ea3y ra trong \u0111i\u1ec1u ki\u1ec7n h\u1ebft s\u1ee9c kh\u1eafc nghi\u1ec7t v\u00e0 hi\u1ec7u su\u1ea5t s\u1ea3n ph\u1ea9m r\u1ea5t th\u1ea5p b\u1edfi v\u00ec t\u00ednh nucleophin c\u1ee7a ion hi\u0111roxyl th\u1ea5p h\u01a1n ami\u0111ua. \u00dd ngh\u0129a th\u1ef1c t\u1ebf c\u1ee7a ph\u1ea3n \u1ee9ng n\u00e0y kh\u00f4ng cao : 320l)c ~N, \\\"O KOH - - - > . K N ' H\u0129 N O K+ Mu\u1ed1i kali c\u1ee7a 2-hi\u0111roxipyri\u0111in (ho\u1eb7c pyri\u0111-2 -on) A nkyl h\u00f3a v\u00e0 aryl h\u00f3a. C\u00e1c t\u00e1c nh\u00e2n nucleophin m\u1ea1nh nh\u01b0 h\u1ee3p ch\u1ea5t c\u01a1 lithi d\u1ec5 d\u00e0ng c\u1ed9ng v\u00e0o pyri\u0111in t\u1ea1o th\u00e0nh mu\u1ed1i 1,2-\u0111ihi\u0111ropyri\u0111in, h\u1ee3p ch\u1ea5t n\u00e0y \u0111\u00f4i khi c\u00f3 th\u1ec3 t\u00e1ch ra \u1edf tr\u1ea1ng th\u00e1i ri\u00eang bi\u1ec7t. Vi\u1ec7c chuy\u1ec3n th\u00e0nh h\u1ec7 th\u01a1m b\u1eb1ng c\u00e1ch t\u00e1ch ion hi\u0111rua nh\u1edd nhi\u1ec7t ho\u1eb7c ch\u1ea5t oxi h\u00f3a : 419","+ c 6H5Li \u1eca \\\\h 101 ^ n ^ c 6h 5 (80%) n\\\" \\\" - vn ^ q h 5 h\u00b0 ? c d ,m \u201e 6 \u201eg Li + Mu\u1ed1i lithi c\u1ee7a 1 ,2 -\u0111ihi\u0111ropyri\u0111in C\u0169ng gi\u1ed1ng nh\u01b0 ph\u1ea3n \u1ee9ng Chichibabin, s\u1ef1 th\u1ebf x\u1ea3y ra \u01b0u vi\u1ec7t \u1edf v\u1ecb tr\u00ed 2 ho\u1eb7c 2, 6 (c\u00f3 d\u01b0 t\u00e1c nh\u00e2n). Ph\u1ea3n \u1ee9ng Grinha (RMgX) c\u0169ng t\u1ea1o th\u00e0nh ankyl- v\u00e0 arylpyri\u0111in nh\u01b0ng \u00edt hi\u1ec7u qu\u1ea3 h\u01a1n. S \u1ef1 th\u00ea halogen ho\u1eb7c nh\u00f3m nitro. Halogen v\u00e0 nh\u00f3m nitro \u1edf v\u1ecb tr\u00ed 2 v\u00e0 4 d\u1ec5 d\u00e0ng b\u1ecb th\u1ebf d\u01b0\u1edbi t\u00e1c d\u1ee5ng c\u1ee7a t\u00e1c nh\u00e2n nucleophin : + CH.ONa N C1 3 N OCH; (95%) + H.. -,0 \u201460 c -> z - HNOt Pyri\u0111-4-on (95%) 3-Halogenpyri\u0111in \u00edt Q\u1ed7 kh\u1ea3 n\u0103ng ph\u1ea3n \u1ee9ng v\u00e0 gi\u1ed1ng v\u1edbi halogenbenzen. Nh\u1edd kh\u1ea3 n\u0103ng ph\u1ea3n \u1ee9ng th\u1ea5p c\u1ee7a v\u1ecb tr\u00ed p m\u00e0 c\u00f3 th\u1ec3 th\u1ebf ch\u1ecdn l\u1ecdc d\u1eabn xu\u1ea5t 3,4-\u0111ihalogen c\u1ee7a pyri\u0111in : 3,4-\u0110ibrompyri\u0111in (65%) T\u00e1c nh\u00e2n nucleophin c\u00f3 t\u00ednh baz\u01a1 m\u1ea1nh t\u01b0\u01a1ng t\u00e1c v\u1edbi 3- v\u00e0 4-haIogenpyri\u0111in theo c\u00e1ch kh\u00e1c. Th\u00ed d\u1ee5 khi cho natri ami\u0111ua trong amoniac l\u1ecfng t\u00e1c d\u1ee5ng v\u1edbi c\u00e1c \u0111\u1ed3ng ph\u00e2n 3- v\u00e0 4-clopyri\u0111in th\u00ec \u0111\u1ec1u nh\u1eadn \u0111\u01b0\u1ee3c c\u00f9ng m\u1ed9t h\u1ed7n h\u1ee3p c\u00e1c s\u1ea3n ph\u1ea9m th\u1ebf. K\u1ebft qu\u1ea3 nh\u01b0 th\u1ebf c\u00f3 th\u1ec3 l\u00e0 do t\u1ea1o th\u00e0nh 3,4-\u0111ehi\u0111ropyri\u0111in trung gian, sau \u0111\u00f3 c\u1ed9ng ion ami\u0111ua v\u00e0 proton. Kh\u00e1c v\u1edbi c\u00e1c th\u00ed d\u1ee5 \u0111\u00e3 x\u00e9t tr\u01b0\u1edbc kia v\u1ec1 s\u1ef1 th\u1ebf nucleophin, trong tr\u01b0\u1eddng h\u1ee3p n\u00e0y ph\u1ea3n \u1ee9ng x\u1ea3y ra theo m\u1ed9t c\u01a1 ch\u1ebf kh\u00e1c, \u0111\u00f3 l\u00e0 s\u1ef1 t\u00e1ch - c\u1ed9ng (EA), t\u01b0\u01a1ng \u0111\u1ed3ng v\u1edbi c\u01a1 ch\u1ebf aryn trong d\u00e3y benzen : 420","NH N NH' 3,4-\u0110ehi\u0111ropyri\u0111in N (25%) 15.5.5 Ph\u1ea3n \u1ee9ng oxi h\u00f3a v\u00e0 kh\u1eed O xi h\u00f3a \u1edf nguy\u00ean t\u1ee7 nit\u01a1. Pyri\u0111in d\u1ec5 d\u00e0ng chuy\u1ec3n th\u00e0nh N-oxit tinh th\u1ec3 d\u01b0\u1edbi t\u00e1c d\u1ee5ng c\u1ee7a peaxit (axit pebenzoic ho\u1eb7c axit peaxetic). Sau n\u00e0y ng\u01b0\u1eddi ta c\u00f3 th\u1ec3 d\u00f9ng H20 2 30% trong axit axetic : CH-\u1ecbCOOH, 65\\\"c ho\u1eb7c + + H20 2 VN N N - HiO 1 o0 Pyri\u0111in N-oxit (95%) T\u00e1ch lo\u1ea1i oxi h\u00f3a. V\u00f2ng pyri\u0111in c\u0169ng gi\u1ed1ng nh\u01b0 benzen r\u1ea5t b\u1ec1n v\u1edbi t\u00e1c d\u1ee5ng c\u1ee7a ch\u1ea5t oxi h\u00f3a \u1edf nhi\u1ec7t \u0111\u1ed9 th\u01b0\u1eddng. \u0110\u1ec3 \u0111\u00e1nh gi\u00e1 t\u00ednh b\u1ec1n t\u01b0\u01a1ng \u0111\u1ed1i c\u1ee7a ch\u00fang v\u1edbi ch\u1ea5t oxi h\u00f3a ng\u01b0\u1eddi ta \u0111\u00e3 d\u00f9ng m\u00f4 h\u00ecnh ph\u00e2n t\u1eed c\u00f3 ch\u1ee9a hai v\u00f2ng benzen v\u00e0 pyri\u0111in. Th\u1eadt v\u1eady, t\u1eeb th\u1eddi Chichibabin \u0111\u00e3 ch\u1ee9ng minh r\u1eb1ng khi oxi h\u00f3a 2-phenylpyri\u0111in b\u1eb1ng pemanganat trong m\u00f4i tr\u01b0\u1eddng ki\u1ec1m th\u00ec v\u00f2ng pyri\u0111in b\u1ecb ph\u00e1 h\u1ee7y, c\u00f2n trong m\u00f4i tr\u01b0\u1eddng axit th\u00ec v\u00f2ng benzen b\u1ecb ph\u00e1 : N (69%) Khi d\u00f9ng m\u00f4 h\u00ecnh kh\u00e1c, th\u00ed d\u1ee5 quinolin, l\u00fac n\u00e0y kh\u00f4ng ph\u1ee5 thu\u1ed9c m\u00f4i tr\u01b0\u1eddng, v\u00f2ng benzen b\u1ecb ph\u00e1 d\u1ec5 h\u01a1n : \u1eccQ KMn04 ^ .\/C O O H Quinolin 100\u00b0 c N COOH (70%) M\u1ea1ch nh\u00e1nh ankylpyri\u0111in b\u1ecb oxi h\u00f3a d\u1ec5 h\u01a1n v\u00f2ng v\u1edbi s\u1ef1 t\u1ea1o th\u00e0nh axit cacboxylic t\u01b0\u01a1ng \u1ee9ng gi\u1ed1ng nh\u01b0 \u0111\u1ed3ng \u0111\u1eb3ng c\u1ee7a benzen. B\u1eb1ng ph\u01b0\u01a1ng ph\u00e1p n\u00e0y, v\u1edbi quy m\u00f4 c\u00f4ng nghi\u1ec7p, t\u1eeb P-picolin ng\u01b0\u1eddi ta \u0111i\u1ec1u ch\u1ebf \u0111\u01b0\u1ee3c axit nicotinic, amit c\u1ee7a n\u00f3 v\u00e0 vitamin pp. M\u1ed9t s\u1ed1 d\u1eabn xu\u1ea5t kh\u00e1c c\u1ee7a axit nicotinic \u0111\u01b0\u1ee3c d\u00f9ng trong y h\u1ecdc, th\u00ed d\u1ee5 cor\u0111iamin l\u00e0 k\u00edch th\u00edch t\u1ed1, nico\u0111in l\u00e0 thu\u1ed1c th\u00f4ng m\u1eadt. 421","CH ^ X O O H \u1ec9 \u1ecbj 1 [0 ] \u00cd J c T N(C2H ,)2 - n h c h 2o h N Nx n' N P-Picolin Axit nicotinic Cor\u0111iamin Nico\u0111in Oxi h\u00f3a y-picolin s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c axit isonicotinic l\u00e0 s\u1ea3n ph\u1ea9m trung gian \u0111\u1ec3 t\u1ed5ng h\u1ee3p ch\u1ebf ph\u1ea9m ch\u1ed1ng lao isoniazit v\u00e0 phtivazit, nialamit l\u00e0 hi\u0111razit ho\u1eb7c hi\u0111razit th\u1ebf c\u1ee7a axit isonicotinic : NHNH2 \/N H N = C H - \/ V -O H OCH N N Isoniazit Phtivazit Ck .NHNHCH2CH2CONHCH2C6H, c N Nialamit K h\u1eed h\u00f3a. Hi\u0111ro h\u00f3a ho\u00e0n to\u00e0n pyri\u0111in \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n v\u1edbi x\u00fac t\u00e1c \u1edf \u0111i\u1ec1u ki\u1ec7n \u00eam d\u1ecbu : 1+ 3H 2 Pt, 20\u00b0c N N \u2014 \u2014 \u2014\u1ec9 2 1 atm H Piperi\u0111in (95%) Trong c\u1ed3ng nghi\u1ec7p, ng\u01b0\u1eddi ta \u0111i\u1ec1u ch\u1ebf p\u1ecbperi\u0111in b\u1eb1ng c\u00e1ch hi\u0111ro h\u00f3a pyridin v\u1edbi niken Raney \u1edf 170 - 200\u00b0c. \u1ede nhi\u1ec7t \u0111\u1ed9 cao h\u01a1n, li\u00ean k\u1ebft c - N b\u1ecb ph\u00e1 v\u1ee1 v\u00e0 t\u1ea1o th\u00e0nh pentylamin v\u00e0 c\u00f3 th\u1ec3 \u0111\u1ebfn pentan v\u00e0 amoniac. V\u00f2ng pyri\u0111in b\u1ecb kh\u1eed d\u1ec1 h\u01a1n benzen, \u0111i\u1ec1u n\u00e0y \u0111\u01b0\u1ee3c minh ch\u1ee9ng b\u1eb1ng ph\u1ea3n \u1ee9ng hi\u0111ro h\u00f3a 2-phenylpyri\u0111in v\u00e0 quinolin : [H] 2-Phenylp\u00ecperi\u0111in C\u1ecc[H] H ,2.3.4-tetrahi\u0111roquinolin 422","15.5.6 C\u00e1c d\u00e2n xu\u1ea5t c\u1ee7a pyri\u0111in Ch\u00fang la ch\u1ec9 ch\u00fa \u00fd \u0111\u1ebfn nh\u1eefng t\u00ednh ch\u1ea5t m\u00e0 d\u1eabn xu\u1ea5t c\u1ee7a benzen kh\u00f4ng c\u00f3. Ankylpyri\u0111in C\u00e1c \u0111\u1ed3ng \u0111\u00e1ng th\u1ea5p c\u1ee7a pyri\u0111in c\u00f3 t\u00ean th\u00f4ng th\u01b0\u1eddng : metylpyri\u0111in l\u00e0 picolin (g\u1ed3m a-, P- v\u00e0 y-picolin), \u0111imetylpyri\u0111in l\u00e0 luti\u0111in (th\u00ed d\u1ee5 2,3- ho\u1eb7c 2,6-luti\u0111in), trimetylpyri\u0111in l\u00e0 colli\u0111in (ph\u1ed5 bi\u1ebfn l\u00e0 2,4,6- ; th\u01b0\u1eddng g\u1ecdi l\u00e0 \u1ef5ytt\u00ed-colli\u0111in). T\u00ednh ch\u1ea5t \u0111\u1eb7c tr\u01b0ng c\u1ee7a ankylpyri\u0111in l\u00e0 t\u00ednh linh \u0111\u1ed9ng c\u1ee7a hi\u0111ro \u1edf nguy\u00ean t\u1eed cacbon li\u00ean k\u1ebft tr\u1ef1c ti\u1ebfp v\u1edbi v\u00f2ng, hay n\u00f3i c\u00e1ch kh\u00e1c \u0111\u00f3 l\u00e0 t\u00ednh axit c\u1ee7a C H - \u1edf v\u1ecb tr\u00ed k\u1ebft h\u1ee3p nh\u00f3m ankyl v\u00e0o v\u00f2ng. Kh\u1ea3 n\u00e3ng t\u00e1ch proton trong d\u00e3y \u0111\u1ed3ng ph\u00e2n picolin gi\u1ea3m theo tr\u1eadt t\u1ef1 \u1ef4- > a- \u00bb P-. Nguy\u00ean nh\u00e2n c\u1ee7a t\u00ednh axit C H - c\u1ee7a nh\u00f3m metyl l\u00e0 do \u1ea3nh h\u01b0\u1edfng h\u00fat electron c\u1ee7a nguy\u00ean t\u1eed nit\u01a1 \u1edf pyri\u0111in l\u00e0m ph\u00e2n c\u1ef1c li\u00ean k\u1ebft c - H, \u0111\u1ed3ng th\u1eddi kh\u00f4ng ch\u1ec9 do hi\u1ec7u \u1ee9ng c\u1ea3m \u1ee9ng (trong tr\u01b0\u1eddng h\u1ee3p n\u00e0y p-picolin chi\u1ebfm v\u1ecb tr\u00ed trung gian) m\u00e0 c\u00f2n do d\u1ea1ng \u0111\u1eb7c bi\u1ec7t c\u1ee7a s\u1ef1 li\u00ean h\u1ee3p, si\u00eau li\u00ean h\u1ee3p th\u1ec3 hi\u1ec7n \u1edf a - v\u00e0 \u1ef4-picolin. T\u00ednh axit C H - c\u1ee7a ch\u00fang t\u0103ng l\u00ean l\u00e0 do t\u00ednh b\u1ec1n l\u1edbn c\u1ee7a baz\u01a1 li\u00ean h\u1ee3p (c\u00e1c anion), trong \u0111\u00f3 m\u1ed9t trong c\u00e1c c\u1ea5u tr\u00fac gi\u1edbi h\u1ea1n mang \u0111i\u1ec7n t\u00edch \u1edf nguy\u00ean t\u1eed nit\u01a1 \u00e2m \u0111i\u1ec7n h\u01a1n (trong tr\u01b0\u1eddng h\u1ee3p p-picolin kh\u00f4ng c\u00f3 \u0111\u01b0\u1ee3 c): H N CH; N CH2 N CH * C ^ ch2 Si\u00f4u li\u00ean h\u1ee3p C\u00e1c c\u1ea5u tr\u00fac c\u1ed9ng h\u01b0\u1edfng c\u1ee7a anion cc-picolin \u1edb \u1ef4-picolin Khi t\u00e1c d\u1ee5ng v\u00f3i baz\u01a1 m\u1ea1nh th\u00ec 2- v\u00e0 4-ankylpyridin chuy\u1ec3n th\u00e0nh anion, c\u00f3 kh\u1ea3 n\u0103ng th\u1ec3 hi\u1ec7n l\u00e0 t\u00e1c nh\u00e2n nucleophin. Ph\u1ea3n \u1ee9ng v\u1edbi ankyl halogenua l\u00e0m k\u00e9o d\u00e0i m\u1ea1ch nh\u00e1nh c\u1ee7a pyri\u0111in, \u0111\u1ed3ng th\u1eddi, c\u00f9ng v\u1edbi nh\u00f3m ankyl c\u00f3 th\u1ec3 \u0111\u01b0a v\u00e0o m\u1ed9t s\u1ed1 nh\u00f3m ch\u1ee9c (kh\u00f4ng d\u1eabn ra \u1edf s\u01a1 \u0111\u1ed3). S\u1ef1 t\u01b0\u01a1ng t\u00e1c c\u1ee7a anion v\u1edbi C 0 2 cho ph\u00e9p nh\u1eadn \u0111\u01b0\u1ee3c axit pyri\u0111ylaxetic : + NaNH- C 4H 9C1 N c h 2c 4h< N CH- NHl N CH\u1ecdNa 1. c o 2 (60% ) 2. H + n ^ c h 2c o o h (45% ) Nh\u1edd s\u1ef1 c\u00f3 m\u1eb7t trung t\u00e2m axit C H - m\u00e0 2- v\u00e0 4-ankylpyri\u0111in c\u00f3 kh\u1ea3 n\u0103ng ph\u1ea3n \u1ee9ng v\u1edbi h\u1ee3p ch\u1ea5t cacbonyl theo ki\u1ec3u ng\u01b0ng t\u1ee5 an\u0111ol. Ph\u1ea3n \u1ee9ng \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n ho\u1eb7c l\u00e0 theo hai giai \u0111o\u1ea1n - v\u1edbi s\u1ef1 t\u1ea1o anion tr\u01b0\u1edbc (nh\u01b0 \u1edf th\u00ed d\u1ee5 tr\u00ean) ho\u1eb7c tr\u1ef1c ti\u1ebfp - khi c\u00f3 m\u1eb7t x\u00fac t\u00e1c axit Liuyt (ZnCl2). S\u1ef1 ng\u01b0ng t\u1ee5 v\u1edbi an\u0111ehit m\u1ea1ch th\u1eb3ng, th\u00ed d\u1ee5 v\u1edbi fomandehit t\u1ea1o th\u00e0nh d\u1eabn xu\u1ea5t p-hidroxiankyl - \u0111\u00f3 l\u00e0 c\u00e1c \u0111\u1ed3ng \u0111\u1eb3ng c\u1ee7a an\u0111ol : 42?","c h 2o f^ h 2s o 4 _Hn ^ 7 r \u0129 ^ I -\u00edX \u201c p N ' \\\"CH3 Z n- N CH2- C H 2OH 2 'N ' 'CH = CH2 a-Picolin 2-(2-Pyri\u0111yl) etanol 2-Vinylpyri\u0111in Ancol \u0111\u01b0\u1ee3c t\u1ea1o th\u00e0nh l\u00fac n\u00e0y r\u1ea5t d\u1ec5 b\u1ecb \u0111ehi\u0111ral h\u00f3a th\u00e0nh 2-vinylpyri\u0111in - l\u00e0 h\u1ee3p ch\u1ea5t \u0111\u1ea7u \u0111\u1ec3 t\u1ed5ng h\u1ee3p c\u00e1c d\u1eabn xu\u1ea5t c\u1ee7a pyri\u0111in v\u1edbi c\u00e1c nh\u00f3m ch\u1ee9c kh\u00e1c nhau \u1edf m\u1ea1ch nh\u00e1nh. Ngo\u00e0i ra, vinylpyridin (\u0111\u1eb7c bi\u1ec7t l\u00e0 \u0111\u1ed3ng ph\u00e2n \u1edf v\u1ecb tr\u00ed 3 m\u00e0 kh\u00f4ng th\u1ec3 t\u1ed5ng h\u1ee3p b\u1eb1ng c\u00e1ch n\u00e0y) \u0111\u01b0\u1ee3c d\u00f9ng l\u00e0m monome cho vi\u1ec7c copolime h\u00f3a v\u1edbi buta\u0111ien \u0111\u1ec3 s\u1ea3n xu\u1ea5t cao su vinylpyri\u0111in. V\u1edbi an\u0111ehit th\u01a1m th\u00ec t\u1ea1o th\u00e0nh ngay d\u1eabn xu\u1ea5t kh\u00f4ng no (t\u01b0\u01a1ng t\u1ef1 ng\u01b0ng t\u1ee5 croton): Q + c 6h , c h o 140 c Q N CH3 N CH = CHC6H5 Hi\u0111roxipyri\u0111in Hi\u1ec7n t\u01b0\u1ee3ng tautome l\u00e0 \u0111\u1eb7c tr\u01b0ng c\u1ee7a t\u1ea5t c\u1ea3 ba \u0111\u1ed3ng ph\u00e2n hi\u0111roxipyri\u0111in. 2- v\u00e0 4-Hi\u0111roxipyri\u0111in tautome h\u00f3a th\u00e0nh d\u1ea1ng 0 X0 , \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 pyri\u0111-2-on v\u00e0 pyri\u0111-4-on. Xu\u1ea5t ph\u00e1t t\u1eeb c\u00e1c d\u1eef ki\u1ec7n ph\u1ed5, trong dung m\u00f4i ph\u00e2n c\u1ef1c v\u00e0 \u1edf tr\u1ea1ng th\u00e1i tinh th\u1ec3 d\u1ea1ng pyri\u0111in c\u00f3 \u01b0u th\u1ebf h\u01a1n, \u0111i\u1ec1u n\u00e0y l\u00e0 do \u00e1i l\u1ef1c c\u1ee7a nit\u01a1 \u0111\u1ed1i v\u1edbi proton l\u1edbn h\u01a1n \u00e1i l\u1ef1c c\u1ee7a oxi \u0111\u1ed1i v\u1edbi proton. OH o OH N O H 3-Hi\u0111roxipyri\u0111in trong dung d\u1ecbch n\u1eb1m c\u00e2n b\u1eb1ng v\u1edbi ion \u1ec9\u01b0\u1ee1ng c\u1ef1c c\u1ee7a n\u00f3, M\u1eb7c d\u00e3u t\u1ed3n t\u1ea1i c\u00e1c \u0111\u1ed3ng ph\u00e2n kh\u00e1c nhau nh\u01b0ng ng\u01b0\u1eddi ta th\u01b0\u1eddng g\u1ecdi m\u1ed9t t\u00ean l\u00e0 hi\u0111roxipyri\u0111in. OH , 0 ' NN H V\u00ec pyri\u0111-2-on l\u00e0 lactam \u0111i\u1ec3n h\u00ecnh (amit v\u00f2ng), c\u00f2n d\u1ea1ng hi\u0111roxi c\u1ee7a n\u00f3 bao g\u1ed3m tautome c\u1ee7a nh\u00f3m amit - nh\u00f3m lactim - C(=NR)OH, c\u00e2n b\u1eb1ng n\u00e0y \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 h\u1ed7 bi\u1ebfn lactim-lactam. D\u1ea1ng tautome n\u00e0y \u0111\u1eb7c tr\u01b0ng kh\u00f4ng nh\u1eefng cho 2-hi\u0111roxipyri\u0111in m\u00e0 c\u00f2n cho c\u00e1c h\u1ec7 d\u1ecb v\u00f2ng kh\u00e1c c\u00f3 ch\u1ee9a nh\u00f3m hi\u0111roxi \u1edf nguy\u00ean t\u1eed cacbon b\u00ean c\u1ea1nh nguy\u00ean t\u1eed nit\u01a1 c\u1ee7a pyri\u0111in : d\u1ea1ng lactim d\u1ea1ng lactam 424","\u0110i\u1ec1u ehi nh\u1eadn quan tr\u1ecdng l\u00e0, v\u1ec1 h\u00ecnh Ih\u1ee9c pyri\u0111on kh\u00f4ng ch\u1ee9a v\u00f2ng pvri\u0111in, trong m\u1ed9l m\u1ee9c \u0111\u1ed9 nh\u1ea5t \u0111\u1ecbnh n\u00f3 \u00edhu\u1ed9c v\u1ec1 h\u1ec7 th\u01a1m. H\u1ec7 electron T\u00ed v\u00f2ng d\u01b0\u1ee3c b\u1ea3o \u0111\u1ea3m b\u1edbi s\u1ef1 li\u00ean h\u1ee3p p-n c\u1ee7a c\u1eb7p electron kh\u00f4ng ph\u00e2n chia \u1edf nguy\u00ean t\u1eed nit\u01a1 v\u1edbi nh\u00f3m cacbonyl. Hi\u1ec7n t\u01b0\u1ee3ng n\u00e0y \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 s\u1ef1 li\u00ean h\u1ee3p ch\u00e9o. \u0110\u1eb7c tr\u01b0ng th\u01a1m c\u1ee7a hi\u0111roxipyri\u0111in th\u1ec3 hi\u1ec7n \u1edb ch\u1ed7 ch\u00fang c\u00f3 kh\u1ea3 n\u0103ng tham gia ph\u1ea3n \u1ee9ng th\u1ebf electrophin v\u00e0 \u0111\u01b0\u1ee3c th\u1ebf d\u1ec5 hon b\u1ea3n th\u00e2n pyri\u0111in : oo HH 3-Nitropyri\u0111-4-on (50%) V\u1ec1 t\u00ednh ch\u1ea5t h\u00f3a h\u1ecdc th\u00ec 3-hi\u0111roxipyri\u0111in gi\u1ed1ng phenol nh\u01b0ng ho\u1ea1t t\u00ednh k\u00e9m h\u01a1n. N\u00f3 cho m\u00e0u t\u00edm v\u1edbi clorua s\u1eaft (III), trong khi \u0111\u00f3 c\u00e1c \u0111\u1ed3ng ph\u00e2n c\u1ee7a n\u00f3 (c\u00e1c pyri\u0111on) ch\u1ec9 cho m\u00e0u \u0111\u1ecf nh\u1ea1t. Aminopyri\u0111in C\u00e1c \u0111\u1ed3ng ph\u00e2n aminopyri\u0111in c\u00f3 t\u00ednh baz\u01a1 v\u1eeba ph\u1ea3i v\u00e0 t\u1ea1o v\u1edbi axit mu\u1ed1i k\u1ebft tinh \u1edf nguy\u00ean t\u1eed nit\u01a1 c\u1ee7a v\u00f2ng. T\u00ednh baz\u01a1 m\u1ea1nh nh\u1ea5t th\u1ec3 hi\u1ec7n \u1edf 2- v\u00e0 \u0111\u1eb7c bi\u1ec7t \u1edf 4-aminopyri\u0111in (pKa = 7,2 v\u00e0 9,1 t\u01b0\u01a1ng \u1ee9ng). C\u00e1c \u0111\u1ed3ng ph\u00e2n n\u00e0y t\u1ea1o cation ch\u1ec9 v\u1edbi m\u1ed9t \u0111\u01b0\u01a1ng l\u01b0\u1ee3ng axit, trong \u0111\u00f3 \u0111i\u1ec7n t\u00edch d\u01b0\u01a1ng gi\u1ea3i t\u1ecfa gi\u1eefa hai nguy\u00ean t\u1eed nit\u01a1 : Cation 4-arninopyri\u0111in 3-Aminopyri\u0111in c\u00f3 t\u00ednh baz\u01a1 y\u1ebfu nh\u1ea5t (pKa = 6,6) \u0111\u00f3 l\u00e0 do \u0111i\u1ec7n t\u00edch kh\u00f4ng th\u1ec3 gi\u1ea3i t\u1ecfa trong axit li\u00ean h\u1ee3p. \u0110\u1ed3ng ph\u00e2n 3- kh\u00e1c \u0111\u1ed3ng ph\u00e2n 2- v\u00e0 4- trong d\u00e3y chuy\u1ec3n h\u00f3a h\u00f3a h\u1ecdc, trong \u0111\u00f3 c\u00f3 ph\u1ea3n \u1ee9ng \u0111iazo h\u00f3a. 3-Aminopyri\u0111in gi\u1ed1ng amin th\u01a1m b\u1eadc m\u1ed9t, t\u1ea1o mu\u1ed1i \u0111iazoni : N a N 0 2, HC1 |^ % |^ N 2 C 1 N \u00b0 ' 5\u00b0c N Pyri\u0111in-3-\u0111iazoni clorua Mu\u1ed1i n\u00e0y c\u0169ng gi\u1ed1ng nh\u01b0 mu\u1ed1i aren\u0111iazoni, c\u00f3 kh\u1ea3 n\u0103ng chuy\u1ec3n h\u00f3a k\u1ec3 c\u1ea3 ph\u1ea3n \u1ee9ng gh\u00e9p. B\u1eb1ng c\u00e1ch n\u00e0y c\u00f3 th\u1ec3 nh\u1eadn \u0111\u01b0\u1ee3c c\u00e1c d\u1eabn xu\u1ea5t c\u00f3 nh\u00f3m ch\u1ee9c kh\u00e1c nhau c\u1ee7a pyri\u0111in. 425","2- v \u00e0 4-Aminopyridin ph\u1ea3n \u1ee9ng v\u1edbi axit nitr\u01a1 theo c\u00e1ch kh\u00e1c : v\u00ec t\u00ednh nh\u1ea1y c\u1ea3m cao c\u1ee7a c\u00e1c v\u1ecb tr\u00ed a- v\u00e0 y- \u0111\u1ed1i v\u1edbi s\u1ef1 t\u1ea5n c\u00f4ng nucleophin n\u00ean mu\u1ed1i \u0111iazoni trung gian \u0111\u01b0\u1ee3c t\u1ea1o th\u00e0nh d\u1ebd d\u00e0ng chuy\u1ec3n sang pyri\u0111on. Nh\u01b0 v\u1eady, trong ph\u1ea3n \u1ee9ng \u0111iazo h\u00f3a 2- v\u00e0 4-aminopyri\u0111in x\u1ea3y ra gi\u1ed1ng amin m\u1ea1ch th\u1eb3ng : N NH2 N aN Q 2.H + + H ,0 No N- H 0 - 5\u00b0c N N2 C\u00e1c aminopyri\u0111in c\u00f3 kh\u1ea3 n\u00e3ng tham gia ph\u1ea3n \u1ee9ng th\u1ebf electrophin v\u00e0o nguy\u00ean t\u1eed cacbon, v\u00e0 c\u0169ng gi\u1ed1ng nh\u01b0 hi\u0111roxipyri\u0111in, ph\u1ea3n \u1ee9ng x\u1ea3y ra d\u1ec5 h\u01a1n b\u1ea3n th\u00e2n pyri\u0111in : \u1ee2 NH2+ 02NT>NH2\u2666\u1ee3 ;: (60%) (20%) N-oxit pyri\u0111in Pyri\u0111in N-oxit th\u01b0\u1eddng \u0111\u01b0\u1ee3c bi\u1ec3u di\u1ec5n \u1edf d\u1ea1ng c\u1ea5u tr\u00fac (I) v\u1edbi li\u00ean k\u1ebft cho nh\u1eadn N - o m\u00e0 kh\u00f4ng ch\u1ec9 r\u00f5 s\u1ef1 ph\u00e2n b\u1ed1 m\u1eadt \u0111\u1ed9 electron trong ph\u00e2n t\u1eed. C\u1ea5u t\u1ea1o chi ti\u1ebft h\u01a1n \u0111\u01b0\u1ee3c m\u00f4 t\u1ea3 b\u1eb1ng s\u1ef1 c\u1ed9ng h\u01b0\u1edfng, c\u00f3 \u0111\u00f3ng g\u00f3p l\u1edbn l\u00e0 c\u1ea5u tr\u00fac (III) v\u00e0 (IV) v\u1edbi \u0111i\u1ec7n t\u00edch \u00e2m \u1edf nguy\u00ean t\u1eed cacbon. 0,993 0,87 0,987 1,01 0 <\u2014 >\u25a0 O t \u201d\u1eef )- > + 1,003 0,K4 NN NN N N I1 I II II .41 o o' o o o 1,880 (I) (II) (IV) (III) Pyri\u0111in N-oxit Pyri\u0111in \u0110i\u1ec3m \u0111\u1ed9c \u0111\u00e1o c\u1ee7a N-oxit l\u00e0 n\u00f3 c\u00f3 th\u1ec3 c\u00f3 \u0111\u1eb7c t\u00ednh cho electron v\u00e0 nh\u1eadn electron t\u00f9y thu\u1ed9c v\u00e0o t\u00e1c nh\u00e2n. Vi\u1ec7c t\u0103ng m\u1eadt \u0111\u1ed9 electron trong v\u00f2ng (\u1edf c\u1ea5u tr\u00fac III v\u00e0 IV) l\u00e0m cho pyri\u0111in N-oxit ti\u1ebfp nh\u1eadn ph\u1ea3n \u1ee9ng th\u1ebf electrophin t\u1ed1t h\u01a1n pyri\u0111in. \u0110i\u1ec1u n\u00e0y l\u00e0m cho pyri\u0111in N-oxit c\u00f3 t\u00ednh baz\u01a1 th\u1ea5p (pKa = 0,8, kho\u1ea3ng 4,5 l\u1ea7n th\u1ea5p h\u01a1n pyri\u0111in). VI v\u1eady, trong m\u1ed1i tr\u01b0\u1eddng axit pyri\u0111in N-oxit ph\u1ea3n \u1ee9ng \u1edf d\u1ea1ng kh\u00f4ng proton h\u00f3a \u1edf v\u1ecb tr\u00ed 2 v\u00e0 4, ngh\u0129a l\u00e0 pyri\u0111in \u00edt \u00e1i l\u1ef1c v\u1edbi ph\u1ea3n \u1ee9ng electrophin h\u01a1n : HNO- PCI, + H2S04, 90' c + POC1 N I (80%) o 426","\u1ede s\u01a1 \u0111\u1ed3 n\u00e0y cho th\u1ea5y c\u00f3 th\u1ec3 lo\u1ea1i b\u1ecf nh\u00f3m oxit \u0111\u1ec3 chuy\u1ec3n v\u1ec1 pyri\u0111in. Ngo\u00e0i vi\u1ec7c kh\u01b0 b\u1eb1ng photpho halogenua c\u00f3 th\u1ec3 d\u00f9ng hi\u0111ro h\u00f3a x\u00fac t\u00e1c tr\u00ean pala\u0111i ho\u1eb7c Ni x\u1ed1p v\u00e0 b\u1eb1ng nh\u1eefng ph\u01b0\u01a1ng ph\u00e1p kh\u00e1c. Vi\u1ec7c l\u1ef1a ch\u1ecdn ch\u1ea5t kh\u1eed ph\u1ee5 thu\u1ed9c v\u00e0o b\u1ea3n ch\u1ea5t c\u1ee7a nh\u00f3m ch\u1ee9c trong ph\u00e2n t\u1eed. Ph\u1ea3n \u1ee9ng c\u1ee7a pyri\u0111in N-oxit v\u1edbi t\u00e1c nh\u00e2n Grinha l\u00e0 m\u1ed9t th\u00ed d\u1ee5 v\u1ec1 s\u1ef1 t\u01b0\u01a1ng t\u00e1c v\u1edbi t\u00e1c nh\u00e2n nucleophin, \u1edf \u0111\u00e2y s\u1ef1 t\u1ea5n c\u00f4ng h\u01b0\u1edbng v\u00e0o v\u1ecb tr\u00ed 2 nh\u1edd s\u1ef1 \u0111\u00f3ng g\u00f3p c\u1ee7a c\u1ea5u tr\u00fac c\u1ed9ng h\u01b0\u1edfng (III): C6H5MgBr H h 7o H N C6H, MgBrOH N C6H5 - h 20 ^ + c 6h 5 N II o OMgBr OH (67%) Ph\u1ea3n \u1ee9ng halogen h\u00f3a b\u1eb1ng t\u00e1c d\u1ee5ng c\u1ee7a thionyl clorua SOC1-, ho\u1eb7c photphoryl clorua POCI3 c\u0169ng l\u00e0 ph\u1ea3n \u1ee9ng quan tr\u1ecdng c\u1ee7a pyri\u0111in N-oxit. Do k\u1ebft qu\u1ea3 O-axyl h\u00f3a m\u00e0 mu\u1ed1i pyri\u0111ini \u0111\u01b0\u1ee3c t\u1ea1o th\u00e0nh trung gian d\u1ec5 d\u00e0ng b\u1ecb t\u1ea5n c\u00f4ng nucleophin v\u00e0o v\u1ecb tr\u00ed 2 v\u00e0 4 : C1 + + SOCl2 + N N cf \\\" s\u00b0 2\u2019\u25a0 HC1 n \\\" C1 N \u1eca I o OSOC1 (50%) (40%) Nh\u01b0 v\u1eady, pyri\u0111in N-oxit l\u00e0 m\u1ed9t t\u00e1c nh\u00e2n qu\u00fd, nh\u1edd n\u00f3 m\u00e0 ta c\u00f3 th\u1ec3 \u0111i\u1ec1u ch\u1ebf c\u00e1c d\u1eabn xu\u1ea5t kh\u00e1c nhau c\u1ee7a pyri\u0111in. 15.5.7 Quinolin v\u00e0 isoquinolin Quinolin v\u00e0 isoquinolin l\u00e0 c\u00e1c \u0111\u1ed3ng ph\u00e2n c\u1ee7a h\u1ec7 ng\u01b0ng t\u1ee5 gi\u1eefa pyri\u0111in v\u1edbi benzen, ch\u00fang ch\u1ec9 kh\u00e1c nhau do c\u00e1ch gh\u00e9p hai v\u00f2ng : Quinolin v\u00e0 isoquinolin g\u1ed3m hai v\u00f2ng th\u01a1m n\u00ean n\u00f3 l\u00e0 h\u1ec7 th\u01a1m, th\u1ecfa m\u00e3n quy t\u1eafc Huckel (10 e\u1ec9ectron 7\u0128 li\u00ean h\u1ee3p), v\u1eeba k\u1ebft h\u1ee3p t\u00ednh ch\u1ea5t h\u00f3a h\u1ecdc c\u1ee7a pyri\u0111in v\u00e0 c\u1ee7a naphtalen. T\u00ednh baz\u01a1 v\u00e0 t\u00ednh nucleophin C\u0169ng gi\u1ed1ng nh\u01b0 pyri\u0111in, t\u00ednh baz\u01a1 v\u00e0 t\u00ednh nucleophin c\u1ee7a quinolin v\u00e0 isoquinolin l\u00e0 do c\u1eb7p \u0111\u00f4i electron c\u1ee7a nguy\u00ean t\u1eed nit\u01a1 kh\u00f4ng tham gia v\u00e0o h\u1ec7 li\u00ean h\u1ee3p. T\u00ednh baz\u01a1 c\u1ee7a ch\u00fang k\u00e9m t\u00ednh baz\u01a1 c\u1ee7a amin b\u00e9o (pKa t\u1eeb 4,9 \u0111\u1ebfn 5,4). V\u1edbi axit m\u1ea1nh quinolin t\u1ea1o mu\u1ed1i v\u00e0 t\u1ea1o mu\u1ed1i N-ankylquinolin b\u1eadc b\u1ed1n v\u1edbi ankyl halogenua. 427","Quinolini hi\u0111rosun\u00edat + CH.Br N Br Quinolin CH3 N-Metylquinolini bromua Ph\u1ea3n \u1ee9ng th\u00ea nucleophin C\u00f3 nhi\u1ec1u y\u1ebfu t\u1ed1 \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn t\u1ed1c \u0111\u1ed9 v\u00e0 h\u01b0\u1edbng ph\u1ea3n \u1ee9ng th\u1ebf v\u00e0o d\u1ecb v\u00f2ng ng\u01b0ng t\u1ee5, v\u00ec v\u1eady \u1edf \u0111\u00e2y ch\u00fang ta ch\u1ec9 x\u00e9t c\u00e1c th\u00ed d\u1ee5 \u0111\u01a1n gi\u1ea3n nh\u1ea5t. Trong hai v\u00f2ng th\u01a1m c\u1ee7a quinolin, v\u00f2ng ch\u1ee9a d\u1ecb t\u1eed thi\u1ebfu electron n do \u0111\u00f3 s\u1ef1 t\u1ea5n c\u00f4ng electrophin, \u0111\u1eb7c bi\u1ec7t trong m\u00f4i tr\u01b0\u1eddng axit m\u1ea1nh s\u1ebd h\u01b0\u1edbng v\u00e0o v\u00f2ng benzen \u1edf c 5 v\u00e0 c 8, ngh\u0129a l\u00e0 b\u00ean c\u1ea1nh v\u1ecb tr\u00ed c\u00e1c v\u00f2ng gh\u00e9p nhau : Ph\u1ea3n \u1ee9ng th\u1ebf electrophin \u1edf quinolin x\u1ea3y ra d\u1ec5 h\u01a1n so v\u1edbi pyri\u0111in nh\u01b0ng kh\u00f3 h\u01a1n nhi\u1ec1u so v\u1edbi naphtalen. Khi cho h\u1ed7n h\u1ee3p nitro h\u00f3a ph\u1ea3n \u1ee9ng v\u1edbi quinolin s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c c\u00e1c d\u1eabn xu\u1ea5t nitro \u0111\u1ed3ng ph\u00e2n v\u1edbi l\u01b0\u1ee3ng b\u1eb1ng nhau : N02 + HNO H2SO4 . 0 + r V \/0 N ol,c N Khi sunfo h\u00f3a quinolin b\u1eb1ng axit sunfuric \u0111\u1eb7c (\u1edf nhi\u1ec7t \u0111\u1ed9 220\u00b0C) ho\u1eb7c oleum (\u1edf 90\u00b0C) ch\u1ec9 nh\u1eadn \u0111\u01b0\u1ee3c axit 8-sunfonic. Trong ki\u1ec3m n\u00f3ng ch\u1ea3y axit n\u00e0y chuy\u1ec3n th\u00e0nh 8-hi\u0111roxiquinolin (ocxin): NaOH n\u00f3ng ch\u1ea3y SO3H OH Axit quinolin-8-sunfonic 8 -Hi\u0111roxiquinolin Ocxin \u0111\u01b0\u1ee3c d\u00f9ng r\u1ed9ng r\u00e3i l\u00e0m thu\u1ed1c th\u1eed cho h\u00f3a ph\u00e2n t\u00edch, n\u00f3 k\u1ebft h\u1ee3p v\u1edbi c\u00e1c ion c\u1ee7a nhi\u1ec1u kim lo\u1ea1i t\u1ea1o th\u00e0nh ph\u1ee9c chelat kh\u00f3 tan : Ph\u1ee9c c\u1ee7a ocxin v\u1edbi ion Mg 2 + 428","B\u1ea3n th\u00e2n ocxin (d\u01b0\u1edbi d\u1ea1ng sun\u00edat) l\u00e0 ch\u1ebf ph\u1ea9m quinozol v\u00e0 d\u1eabn xu\u1ea5t nitrocxolin \u0111\u01b0\u1ee3c d\u00f9ng l\u00e0m ph\u01b0\u01a1ng ti\u1ec7n kh\u00e1ng khu\u1ea9n trong y h\u1ecdc : N02 + SO4- N OH H N c 8 -Hi\u0111roxiquinolini sun\u00edat (quinozol) 8-Hi\u0111roxi-5-nitroquinolin Ph\u1ea3n \u1ee9ng halogen h\u00f3a quinolin r\u1ea5t ph\u1ee9c t\u1ea1p, ph\u1ee5 thu\u1ed9c v\u00e0o \u0111i\u1ec1u ki\u1ec7n ti\u1ebfn h\u00e0nh ph\u1ea3n \u1ee9ng. Khi brom h\u00f3a trong axit sunfuric \u0111\u1eb7c v\u00e0 \u0111un n\u00f3ng th\u00ec nh\u1eadn \u0111\u01b0\u1ee3c h\u1ed7n h\u1ee3p 5-brom- v\u00e0 8 -bromquinolin v\u1edbi t\u1ef7 l\u1ec7 x\u1ea5p x\u1ec9 1\/1. N\u1ebfu \u0111un s\u00f4i quinolin v\u00e0 brom khi kh\u00f4ng c\u00f3 axit th\u00ec s\u1ebd th\u1ebf v\u00e0o v\u00f2ng pyri\u0111in : CC14 r Br o n + Br? 3-Bromquinolin (82%) Ph\u1ea3n \u1ee9ng th\u00ea nucleophin B\u1eb1ng t\u00e1c d\u1ee5ng c\u1ee7a natri ami\u0111ua trong xilen \u1edb 100\u00b0c ta s\u1ebd \u0111\u01b0a tr\u1ef1c ti\u1ebfp nh\u00f3m amino v\u00e0o v\u1ecb tr\u00ed 2 c\u1ee7a quinolin gi\u1ed1ng nh\u01b0 \u0111\u1ed1i v\u1edbi pyri\u0111in (x. m\u1ee5c 15.5.4): _ T . T\u201e xilen f:\u00ed\u00ed^ v\u00ec i \u00ed5\u00edl + NaNH2 \u2014100 c > ^ I AI NH2 N 2-Aminoquinolin (40%) Ph\u1ea3n \u1ee9ng hi\u0111roxyl h\u00f3a quinolin \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n khi \u0111un n\u00f3ng v\u1edbi kali hi\u0111roxit n\u00f3ng ch\u1ea3y, ph\u1ea3n \u1ee9ng x\u1ea3y ra theo ki\u1ec3u c\u1ed9ng h\u1ee3p 1 ,2 ; s\u1ea3n ph\u1ea9m cu\u1ed1i c\u00f9ng \u1edf d\u1ea1ng lactam b\u1ec1n h\u01a1n : KOH H+ 250\\\"c H No nT OK H Quinol-2-on (50%) V\u1edbi isoquinolin, trong \u0111i\u1ec1u ki\u1ec7n t\u01b0\u01a1ng t\u1ef1 nh\u01b0 tr\u00ean, khi amin h\u00f3a v\u00e0 hi\u0111roxyl h\u00f3a ch\u1ec9 thu \u0111\u01b0\u1ee3c s\u1ea3n ph\u1ea9m th\u1ebf \u1edf v\u1ecb tr\u00ed 1 : NH2 o 1-Aminoisoquinolin lsoquino]-l-on 429","15.6 Nh\u00f3m pyran C\u00e1c d\u1ecb v\u00f2ng 6 c\u1ea1nh ch\u1ee9a oxi l\u00e0 pyran. V\u1edbi d\u1ecb v\u00f2ng 6 c\u1ea1nh kh\u00f4ng no ch\u1ee9a m\u1ed9t oxi ta c\u00f3 2H-pyran v\u00e0 4H-pyran, c\u0169ng c\u00f2n \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 a-pyran v\u00e0 y-pyran. :\u00d3: \u00f3: 0 o 1 4H-Pyran 2H-Pyran M\u1eb7c d\u00f9 ph\u00e2n t\u1eed pyran c\u00f3 li\u00ean h\u1ee3p p-7T v\u00e0 s\u1ed1 electron tham gia trong h\u1ec7 li\u00ean h\u1ee3p l\u00e0 s\u00e1u (th\u1ecfa m\u00e3n quy t\u1eafc Huckel) nh\u01b0ng pyran kh\u00f4ng thu\u1ed9c h\u1ee3p ch\u1ea5t th\u01a1m v\u00ec s\u1ef1 li\u00ean h\u1ee3p b\u1ecb ng\u1eaft qu\u00e3ng do 2H-pyran c\u00f3 C2 lai h\u00f3a sp3 v\u00e0 4H-pyran c\u00f3 C4 lai h\u00f3a sp3. Ng\u01b0\u1ee3c l\u1ea1i, c\u1ea3 hai d\u1ecb v\u00f2ng kh\u00f4ng th\u01a1m \u0111\u1ec1u kh\u00f4ng b\u1ec1n v\u1ec1 m\u1eb7t nhi\u1ec7t \u0111\u1ed9ng v\u00e0 l\u00e0 h\u1ee3p ch\u1ea5t kh\u00f4ng no c\u00f3 kh\u1ea3 n\u00e3ng ph\u1ea3n \u1ee9ng cao. 4H-Pyran b\u1ecb ph\u00e2n h\u1ee7y khi ch\u01b0ng c\u1ea5t (kho\u1ea3ng 80\u00b0C) v\u00e0 k\u1ec3 c\u1ea3 khi \u1ee9 ngo\u00e0i kh\u00f4ng kh\u00ed, c\u00f2n 2H-pyran \u0111\u1ebfn nay v\u1eabn ch\u01b0a \u0111i\u1ec1u ch\u1ebf \u0111\u01b0\u1ee3c. sp.3 C|| o \\\\j S sp V\u1edd \u1ecf \u01a1 4H-Pyran 2H-Pyran Tuy v\u1eady, ng\u01b0\u1eddi ta c\u0169ng bi\u1ebft \u0111\u01b0\u1ee3c v\u00e0 g\u1eb7p trong t\u1ef1 nhi\u00ean c\u00e1c h\u1ee3p ch\u1ea5t c\u1ee7a d\u00e3y pyran c\u00f3 t\u00ednh th\u01a1m v\u1edbi m\u1ed9t m\u1ee9c \u0111\u1ed9 n\u00e0o \u0111\u1ea5y, th\u00ed d\u1ee5 nh\u01b0 mu\u1ed1i c\u1ee7a pyrili v\u00e0 d\u1eabn xu\u1ea5t ch\u1ee9a oxi c\u1ee7a pyran l\u00e0 c\u00e1c pyron. 15.6.1 Mu\u1ed1i pyrili v\u00e0 pyron Kh\u00e1c v\u1edbi pyran, mu\u1ed1i pyrili b\u1ec1n v\u1ec1 m\u1eb7t nhi\u1ec7t \u0111\u1ed9ng h\u1ecdc. Cation pyrili (h\u00ecnh 15.2a) \u1ee9ng v\u1edbi ti\u00eau chu\u1ea9n th\u01a1m. C\u1eb7p \u0111\u00f4i electron c\u1ee7a nguy\u00ean t\u1eed oxi chi\u1ebfm obitan lai h\u00f3a sp2 n\u1eb1m trong m\u1eb7t ph\u1eb3ng c\u1ee7a v\u00f2ng. Obitan p kh\u00f4ng lai h\u00f3a ph\u00e2n b\u1ed1 song song v\u1edbi obitan p c\u1ee7a c\u00e1c nguy\u00ean t\u1eed cacbon (h\u00ecnh 15.2b) v\u00e0 t\u1ea1o th\u00e0nh \u0111\u00e1m m\u00e2y gi\u1ea3i t\u1ecfa \u0111\u1ed3ng nh\u1ea5t v\u1edbi ch\u00fang (h\u00ecnh 15.2c). ob itan p, ho\u1eb7c obitan sp C>0+O a) b) H \u00ecnh 15.2 Cation pyrili a) C\u00f4ng th\u1ee9c c\u1ea5u tr\u00fac ; b) c \u1ea5 u h\u00ecnh electron c\u1ee7a nguy\u00ean t\u1eed o xi ; c) S\u1ef1 t\u1ea1o th\u00e0nh h\u1ec7 gi\u1ea3i t\u1ecfa 430","S\u1ef1 t\u1ed3n t\u1ea1i h\u1ee3p ch\u1ea5t pyrili \u0111\u00e3 \u0111\u01b0\u1ee3c bi\u1ebft t\u1eeb cu\u1ed1i th\u1ebf k\u1ef7 19, \u0111\u1ea1i di\u1ec7n \u0111\u1ea7u ti\u00ean c\u1ee7a h\u1ee3p ch\u1ea5t n\u00e0y \u0111\u01b0\u1ee3c t\u1ed5ng h\u1ee3p b\u1eb1ng c\u00e1ch cho \u0111imetyl sun\u00edat ph\u1ea3n \u1ee9ng v\u1edbi 2,6-\u0111imetyl-y-pyron. Tuy nhi\u00ean, mu\u1ed1i pyrili kh\u00f4ng th\u1ebf (peclorat) \u0111\u1ea7u ti\u00ean ch\u1ec9 m\u1edbi \u0111\u01b0\u1ee3c t\u1ed5ng h\u1ee3p v\u00e0o n\u0103m 1953 : o OCH3 + (CH30 )2S02 CH3 0 S0 3 h 3c o c h 3 h 3c c h 3 2,6-\u0110imetyl-y-pyron 2.6-\u0110imetyl-4-metoxipyrili metylhi\u0111rosun\u00edat CIO 0 Pyrili peclorat Pyrili peclorat b\u1ec1n nhi\u1ec7t \u0111\u1ed9ng v\u00e0 ch\u1ec9 b\u1ecb ph\u00e2n h\u1ee7y \u1edb 275\u00b0c. Mu\u1ed1i pyrili th\u1ebf c\u00f2n b\u1ec1n h\u01a1n, \u0111\u1eb7c bi\u1ec7t \u1edf v\u1ecb tr\u00ed 2, 4, 6, k\u1ec3 c\u1ea3 h\u1ee3p ch\u1ea5t ng\u01b0ng t\u1ee5 v\u1edbi v\u00f2ng benzen. Mu\u1ed1i pyrili b\u1ec1n trong m\u00f4i tr\u01b0\u1eddng axit. C\u00e1c h\u1ee3p ch\u1ea5t ch\u1ee9a oxi c\u1ee7a pyran g\u1ed3m c\u00f3 a-pyron (\u0111\u00fang h\u01a1n ph\u1ea3i g\u1ecdi l\u00e0 2H-pyran-2-on) v\u00e0 \u1ef4-pyron (4H-pyran-4-on). Trong c\u1ea3 hai ph\u00e2n t\u1eed, t\u1ea5t c\u1ea3 c\u00e1c nguy\u00ean t\u1eed \u0111\u1ec1u \u1edf tr\u1ea1ng th\u00e1i lai h\u00f3a sp2, do \u0111\u00f3 c\u00f3 th\u1ec3 n\u00f3i v\u1ec1 s\u1ef1 li\u00ean h\u1ee3p c\u1ee7a c\u00e1c electron n c\u1ee7a v\u00f2ng v\u1edbi c\u1eb7p \u0111\u00f4i electron kh\u00f4ng ph\u00e2n chia c\u1ee7a oxi trong v\u00f2ng v\u00e0 v\u1edbi nh\u00f3m cachonyl. D\u1ea1ng gi\u1ea3i t\u1ecfa c\u1ee7a \u0111\u00e1m m\u00e2y clectron c\u1ee7a h\u1ec7 nh\u01b0 th\u1ebf l\u00e0m cho n\u00f3 c\u00f3 d\u1eb7c tr\u01b0ng th\u01a1m m\u1ed9t ph\u1ea7n, v\u00ec v\u1eady pyron thu\u1ed9c v\u1ec1 lo\u1ea1i h\u1ee3p ch\u1ea5t \u201cpseudoaromatic\u201d. \u1eef *( 0 2H-Pyran-2-on (a-pyron) 4H-Pyran-4-on (y-pyron) M\u1ed9t v\u00e0i chuy\u1ec3n h\u00f3a h\u00f3a h\u1ecdc ch\u1ee9ng t\u1ecf t\u00ednh th\u01a1m c\u1ee7a pyron. Th\u00ed d\u1ee5, khi brom h\u00f3a y-pyron s\u1ebd nh\u1eadn \u0111\u01b0\u1ee3c d\u1ea9n xu\u1ea5t mono- v\u00e0 \u0111ibrom (s\u1ea3n ph\u1ea9m ch \u00edn h ): o + Br FeCl3, 100\u00b0c - HBr Nh\u00f3m cacbonyl c\u1ee7a y-pyron kh\u00f4ng tham gia ph\u1ea3n \u1ee9ng t\u1ea1o oxim, phenylhi\u0111razon, baz\u01a1 Sip. N\u00f3 th\u1ec3 hi\u1ec7n t\u00ednh baz\u01a1 y\u1ebfu (pKa c\u1ee7a y-pyron l\u00e0 - 0,3), t\u1ea1o mu\u1ed1i k\u1ebft tinh v\u1edbi nhi\u1ec1u axit v\u00f4 c\u01a1 v\u00e0 h\u1eefu c\u01a1, th\u00ed d\u1ee5 : + OH + HC1 C1 29-HHC r2 431","\u0110\u1eb7c t\u00ednh th\u01a1m v\u00e0 Unh baz\u01a1 c\u1ee7a a-pyron th\u1ed5 hi\u1ec7n y\u1ebfu h\u01a1n. n\u00f3 c\u00f3 t\u00ednh ch\u1ea5t c\u1ee7a \u00f4-lacton kh\u00f4ng no. Ph\u1ea3n \u1ee9ng v\u1edbi t\u00e1c nh\u00e2n nucleophin g\u00e2y n\u00ean s\u1ef1 \u0111\u1ee9t li\u00ean k\u1ebft c - o c\u1ee7a v\u00f2ng v\u00e0 ph\u1ea3n \u1ee9ng n\u00e0y c\u0169ng x\u1ea3y ra khi th\u1ee7y ph\u00e2n b\u1eb1ng ki\u1ec1m : + HO r OH 0 = CH COOH 00 0o B\u1ea3n th\u00e2n a-pyron v\u00e0 \u0111\u1ed5ng \u0111\u1ea3ng t\u1ef1 polime h\u00f3a ch\u1eadm khi b\u1ea3o qu\u1ea3n, tham gia ph\u1ea3n \u1ee9ng t\u1ed5ng h\u1ee3p \u0111ien, \u0111i\u1ec1u n\u00e0y ch\u1ee9ng t\u1ecf n\u00f3 c\u00f3 \u0111\u1eb7c t\u00ednh kh\u00f4ng no. 15.6.2 C\u00e1c d\u1eabn xu\u1ea5t c\u1ee7a benzopyran H\u1ec7 ng\u01b0ng t\u1ee5 c\u1ee7a v\u00f2ng benzen v\u1edbi v\u00f2ng pyran r\u1ea5t ph\u1ed5 bi\u1ebfn trong h\u1ee3p ch\u1ea5t thi\u00ean nhi\u00ean. Hi\u1ec7n nay ng\u01b0\u1eddi ta v\u1eabn d\u00f9ng t\u00ean h\u1ec7 th\u1ed1ng l\u00e0 bemopyran. I\u01afPAC c\u00f2n cho ph\u00e9p s\u1eed d\u1ee5ng l\u00ean th\u01b0\u1eddng l\u00e0 cromen (c\u00e1c \u0111\u1ed5ng ph\u00e2n 2H- v\u00e0 4H-) d\u00f9ng cho c\u00e1c d\u1ea1i di\u1ec7n kh\u00f4ng no v\u00e0 croman cho c\u00e1c d\u1ecb v\u00f2ng no. 2H-l-Benzopyran C\u1ecf o. (2I\u1ec8-cromcn) 4H-l-Benzopyran 3,4-\u0110ihi\u0111ro-2H-1-benzopyran (4H-cromen) (croman) 4H - 1 -Benzopyran-4~on 2,3-\u0110ihi\u0111ro-4H-1-benzopyran-4-on (cromon) Flavonoit l\u00e0 m\u1ed9t nh\u00f3m \u0111\u1eb7c bi\u1ec7t c\u1ee7a benzopyran, l\u00e0 d\u1eabn xu\u1ea5t c\u1ee7a\/7avan, \u0111\u00f3 l\u00e0 croman c\u00f3 nh\u00f3m th\u1ebf phenyl \u1edf v\u1ecb tr\u00ed 2. D\u1eabn xu\u1ea5t 0X0 c\u1ee7a flavan l\u00e0 \/ lavanon v\u00e0 \u0111\u1ed3ng \u0111\u1eb3ng kh\u1ed3ng no c\u1ee7a n\u00f3 l\u00e0\u00fdlavon : Flavan Flavanon Flavon (2,3-\u0111ihi\u0111ro-2-phenyl- (2 -phenyl- 4H -1-benzopyran-4-on) 4H -1-benzopyran-4-on) Hi\u1ec7n nay s\u1ed1 \u00edlavonoit \u0111\u1ea1t \u0111\u1ebfn h\u00e0ng v\u00e0i ngh\u00ecn ch\u1ea5t. S\u1ef1 kh\u00e1c nhau c\u1ee7a c\u00e1c h\u1ee3p ch\u1ea5t thi\u00ean nhi\u00ean n\u00e0y l\u00e0 do c\u00f3 m\u1eb7t m\u1ed9t s\u1ed1 nh\u00f3m hi\u0111roxi v\u00e0 metoxi \u1edf c\u00e1c v\u1ecb tr\u00ed 3, 5, 7, 3\u2019, 4 \u2019 v\u00e0 5 \u2019. Ph\u1ed5 bi\u1ebfn l\u00e0 quercetin v\u00e0 naringenin : 432","OH o OH o Quercetin Naringenin 3,5,7-trihi\u0111roxi-2-(3',4'-\u0111ihi\u0111roxiphenyl)- 2,3-dihi\u0111ro-5,7-\u0111ihi\u0111roxi-2-(4'-hi\u0111roxiphenyl)- 4H -1-benzopyran-4-on 41 \u1ec9-1-benzopyran-4-on Cromcn t\u01b0\u01a1ng t\u1ef1 pyran, l\u00e0 h\u1ee3p ch\u1ea5t kh\u00f4ng b\u1ec1n. trong khi \u0111\u00f3 nhi\u1ec1u mu\u1ed1i c\u1ee7a d\u1ea7n xu\u1ea5t X0 0 v\u00e0 benzopyrili \u0111\u00f3ng vai tr\u00f2 quan tr\u1ecdng trong ho\u1ea1t \u0111\u1ed9ng s\u1ed1ng c\u00f9a th\u1ef1c v\u1eadt. C\u00f3 nhi\u1ec1u h\u1ee3p ch\u1ea5t trong s\u1ed1 c\u00e1c d\u1eabn xu\u1ea5t c\u1ee7a bcn\/.opyran c\u00f3 ho\u1ea1t t\u00ednh sinh h\u1ecdc c\u1ee9a c\u00e1c d\u1ea1ng kh\u00e1c nhau. C\u00e1c d\u1eabn xu\u1ea5t c\u1ee7a croman H\u1ec7 d\u1ecb v\u00f2ng croman thu\u1ed9c lo\u1ea1i tocophero\u1eca c\u0169ng c\u00f2n \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 nh\u00f3m vitamin E. \u0110\u01b0\u1ee3c bi\u1ebft nhi\u1ec1u nh\u1ea5t l\u00e0 a-tocopherol, c\u00f3 trong h\u1ea1t l\u00faa m\u1ea1ch, g\u1ea1o v\u00e0 trong nhi\u1ec1u d\u1ea7u th\u1ef1c v\u1eadt kh\u00e1c nhau. \u0110\u1ea1i di\u1ec7n kh\u00e1c c\u1ee7a nh\u00f3m n\u00e0y c\u00f3 ch\u1ee9a s\u1ed1 nh\u00f3m metyl kh\u00e1c nhau trong v\u00f2ng v\u00e0 d\u01b0\u1ee3c ph\u00e0n bi\u1ec7t b\u1eb1ng m\u1ee9c \u0111\u1ed9 kh\u00f4ng b\u00e3o h\u00f2a c\u1ee7a m\u1ea1ch nh\u00e1nh : Nh\u01b0\u1ee3c \u0111i\u1ebfm c\u1ee7a tocopherol l\u00e0 g\u00e2y v\u00f4 sinh v\u00e0 ph\u00e1 h\u1ee7y c\u00e1c ch\u1ee9c n\u00e3ng c\u1ee7a c\u01a1 th\u1ec3. Nh\u01b0ng ng\u01b0\u1eddi ta c\u0169ng th\u1ea5y r\u1eb1ng tocopherol \u0111\u00f3ng vai tr\u00f2 ch\u1ea5t ch\u1ed1ng oxi h\u00f3a khi k\u00ecm h\u00e3m qu\u00e1 tr\u00ecnh oxi h\u00f3a lipit. Ng\u01b0\u1eddi ta d\u00f9ng axetat a-tocopherol \u0111\u1ec3 l\u00e0m thu\u1ed1c. H\u1ec7 croman ng\u01b0ng t\u1ee5 v\u1edbi v\u00f2ng xiclohexen \u0111\u01b0\u1ee3c t\u00ecm th\u1ea5y trong ph\u00e2n t\u1eed tetrahi\u0111ro- cannabinol, l\u00e0 ngu\u1ed3n g\u1ed1c c\u1ee7a Ih\u1ef1c v\u1eadt. Nh\u01b0ng \u0111\u00e1ng ti\u1ebfc, n\u00f3 l\u00e0 th\u00e0nh ph\u1ea7n g\u00e2y \u1ea3o gi\u00e1c c\u1ee7a c\u1ea7n sa : CH3 Tetrahi\u0111rocannabinol C\u00e1c cumarin M\u1ed9t m\u1ea3nh d\u1ecb v\u00f2ng c\u1ee7a ph\u00e2n t\u1ee9 cumarin l\u00e0m ta nh\u1edb \u0111\u1ebfn h\u1ee3p ch\u1ea5t ch\u01b0a no h\u01a1n l\u00e0 h\u1ed9 gi\u1ea3 th\u01a1m (pseudoaromatic). Nh\u01b0 l\u00e0 m\u1ed9t \u00f4-lacton di\u00ean h\u00ecnh, cumarin d\u1ec5 b\u1ecb th\u1ee7y ph\u00e2n chuy\u1ec3n th\u00e0nh mu\u1ed1i c\u1ee7a axit cumarinic c\u00f3 c\u1ea5u h\u00ecnh cis \u1edf n\u1ed1i \u0111\u00f4i. Axit t\u1ef1 do kh\u00f4ng t\u00e1ch ra \u0111\u01b0\u1ee3c v\u00ec n\u00f3 t\u1ef1 \u0111\u00f3ng v\u00f2ng th\u00e0nh lacton ban \u0111\u1ea7u : 433"]
Search
Read the Text Version
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 16
- 17
- 18
- 19
- 20
- 21
- 22
- 23
- 24
- 25
- 26
- 27
- 28
- 29
- 30
- 31
- 32
- 33
- 34
- 35
- 36
- 37
- 38
- 39
- 40
- 41
- 42
- 43
- 44
- 45
- 46
- 47
- 48
- 49
- 50
- 51
- 52
- 53
- 54
- 55
- 56
- 57
- 58
- 59
- 60
- 61
- 62
- 63
- 64
- 65
- 66
- 67
- 68
- 69
- 70
- 71
- 72
- 73
- 74
- 75
- 76
- 77
- 78
- 79
- 80
- 81
- 82
- 83
- 84
- 85
- 86
- 87
- 88
- 89
- 90
- 91
- 92
- 93
- 94
- 95
- 96
- 97
- 98
- 99
- 100
- 101
- 102
- 103
- 104
- 105
- 106
- 107
- 108
- 109
- 110
- 111
- 112
- 113
- 114
- 115
- 116
- 117
- 118
- 119
- 120
- 121
- 122
- 123
- 124
- 125
- 126
- 127
- 128
- 129
- 130
- 131
- 132
- 133
- 134
- 135
- 136
- 137
- 138
- 139
- 140
- 141
- 142
- 143
- 144
- 145
- 146
- 147
- 148
- 149
- 150
- 151
- 152
- 153
- 154
- 155
- 156
- 157
- 158
- 159
- 160
- 161
- 162
- 163
- 164
- 165
- 166
- 167
- 168
- 169
- 170
- 171
- 172
- 173
- 174
- 175
- 176
- 177
- 178
- 179
- 180
- 181
- 182
- 183
- 184
- 185
- 186
- 187
- 188
- 189
- 190
- 191
- 192
- 193
- 194
- 195
- 196
- 197
- 198
- 199
- 200
- 201
- 202
- 203
- 204
- 205
- 206
- 207
- 208
- 209
- 210
- 211
- 212
- 213
- 214
- 215
- 216
- 217
- 218
- 219
- 220
- 221
- 222
- 223
- 224
- 225
- 226
- 227
- 228
- 229
- 230
- 231
- 232
- 233
- 234
- 235
- 236
- 237
- 238
- 239
- 240
- 241
- 242
- 243
- 244
- 245
- 246
- 247
- 248
- 249
- 250
- 251
- 252
- 253
- 254
- 255
- 256
- 257
- 258
- 259
- 260
- 261
- 262
- 263
- 264
- 265
- 266
- 267
- 268
- 269
- 270
- 271
- 272
- 273
- 274
- 275
- 276
- 277
- 278
- 279
- 280
- 281
- 282
- 283
- 284
- 285
- 286
- 287
- 288
- 289
- 290
- 291
- 292
- 293
- 294
- 295
- 296
- 297
- 298
- 299
- 300
- 301
- 302
- 303
- 304
- 305
- 306
- 307
- 308
- 309
- 310
- 311
- 312
- 313
- 314
- 315
- 316
- 317
- 318
- 319
- 320
- 321
- 322
- 323
- 324
- 325
- 326
- 327
- 328
- 329
- 330
- 331
- 332
- 333
- 334
- 335
- 336
- 337
- 338
- 339
- 340
- 341
- 342
- 343
- 344
- 345
- 346
- 347
- 348
- 349
- 350
- 351
- 352
- 353
- 354
- 355
- 356
- 357
- 358
- 359
- 360
- 361
- 362
- 363
- 364
- 365
- 366
- 367
- 368
- 369
- 370
- 371
- 372
- 373
- 374
- 375
- 376
- 377
- 378
- 379
- 380
- 381
- 382
- 383
- 384
- 385
- 386
- 387
- 388
- 389
- 390
- 391
- 392
- 393
- 394
- 395
- 396
- 397
- 398
- 399
- 400
- 401
- 402
- 403
- 404
- 405
- 406
- 407
- 408
- 409
- 410
- 411
- 412
- 413
- 414
- 415
- 416
- 417
- 418
- 419
- 420
- 421
- 422
- 423
- 424
- 425
- 426
- 427
- 428
- 429
- 430
- 431
- 432
- 433
- 434
- 435
- 436
- 437
- 438
- 439
- 440
- 441
- 442
- 443
- 444
- 445
- 446
- 447
- 448
- 449
- 450
- 451
- 452
- 453
- 454
- 455
- 456
- 457
- 458
- 459
- 460
- 461
- 462
- 463
- 464
- 465
- 466
- 467
- 468
- 469
- 470
- 471
- 472
- 473
- 474
- 475
- 476
- 477
- 478
- 479
- 480
- 481
- 482
- 483
- 484
- 485
- 486
- 487
- 488
- 489
- 490
- 491
- 492
- 493
- 494
- 495
- 496
- 497
- 498
- 499
- 500
- 501
- 502
- 503
- 504
- 505
- 506
- 507
- 508
- 509
- 510
- 511
- 512
- 513
- 514
- 515
- 516
- 517
- 518
- 519
- 520
- 521
- 522
- 523
- 524
- 525
- 526
- 527
- 528
- 529
- 530
- 531
- 532
- 533
- 534
- 535
- 536
- 537
- 538
- 539
- 540
- 541
- 542
- 543
- 544
- 545
- 546
- 547
- 548
- 549
- 550
- 551
- 552
- 553
- 554
- 555
- 556
- 557
- 558
- 559
- 560
- 561
- 562
- 563
- 564
- 565
- 566
- 567
- 568
- 569
- 570
- 571
- 572
- 573
- 574
- 575
- 576
- 577
- 578
- 579
- 580
- 581
- 582
- 583
- 584
- 585
- 586
- 587
- 588
- 589
- 590
- 591
- 592
- 593
- 594
- 595
- 596
- 597
- 598
- 599
- 600
- 601
- 602
- 603
- 604
- 605
- 606
- 607
- 608
- 609
- 610
- 611
- 612
- 613
- 614
- 615
- 616
- 617
- 618
- 619
- 620
- 621
- 622
- 623
- 624
- 625
- 626
- 627
- 628
- 629
- 630
- 631
- 632
- 633
- 634
- 635
- 636
- 637
- 638
- 639
- 640
- 641
- 642
- 643
- 644
- 645
- 646
- 647
- 648
- 649
- 650
- 651
- 652
- 653
- 654
- 655
- 656
- 657
- 658
- 659
- 660
- 661
- 662
- 663
- 664
- 665
- 666
- 667
- 668
- 669
- 670
- 671
- 672
- 673
- 674
- 675
- 676
- 677
- 678
- 679
- 680
- 681
- 682
- 683
- 684
- 685
- 686
- 687
- 688
- 689
- 690
- 691
- 692
- 693
- 694
- 695
- 696
- 697
- 698
- 699
- 700
- 701
- 702
- 703
- 704
- 705
- 706
- 707
- 708
- 709
- 710
- 711
- 712
- 713
- 714
- 715
- 716
- 717
- 718
- 719
- 720
- 721
- 722
- 723
- 724
- 725
- 726
- 727
- 728
- 729
- 730
- 731
