台灣大學開放式課程 有機化學乙 蔡蘊明教授 本著作除另有註明, 作者皆為蔡蘊明教授, 所有內容皆採用創用 CC 姓名標示 - 非商業使用 - 相同方式分享 3.0 台灣授權條款釋出

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1 台灣大學開放式課程 有機化學乙 蔡蘊明教授 本著作除另有註明, 作者皆為蔡蘊明教授, 所有內容皆採用創用 CC 姓名標示 - 非商業使用 - 相同方式分享 3.0 台灣授權條款釋出

2 Chapter 16 Aldehydes and Ketones Nucleophilic addition to the carbonyl group Nomenclature carbonyl group ( 羰基 ) aldehyde 醛 ' ketone 酮 Aldehydes 3 C IUPAC: methanal ethanal propanal (formaldehyde) (acetaldehyde) (propionaldehyde) C 3 C 2

3 C 3 C 2 C 2 (butyraldehyde) benzenecarbaldehyde (benzaldehyde) cyclohexanecarbaldehyde

4 Ketones C 3 CC 3 C 3 C 2 CC 3 2-butanone (ethyl methyl ketone or methyl ethyl ketone; MEK) bp 80 o C 常用溶劑 C C 3 CC 2 C=C 2 4-penten-2-one C 3 propanone (acetone) bp 56 o C 常用溶劑 acetophenone 苯乙酮 benzophenone

5 As substituent alkanoyl (acyl) methanoyl (formyl) 3 C ethanoyl (acetyl = Ac) Ph benzoyl = Bz S 3 2-methanoylbenzoic acid (o-formylbenzoic acid) 4-ethanoylbenzenesulfonic acid (p-acetylbenzenesulfonic acid)

6 Physical properties Polar δ δ + ' ydrogen bonding with water soluble in water when small 3 C C 3 Some aldehydes and ketones have pleasant fragrances Z-jasmone (jasmine ordor) benzaldehyde (almond ordor) 3 C vanillin cinnamaldehyde

7 Structure ' C planar π bond ~365 kj/mol cf. C=C ~252 kj/mol C 387 kj/mol (in 3 C C 3 ) ' '

8 Preparation of aldehydes xidation of alcohols C 3 (C 2 ) 5 C 2 PCC C 2 Cl 2 C 3 (C 2 ) 5 C 93% zonolysis of olefin 1) 3 2) Zn

9 eduction of acid or derivatives or ' LiAl 4 C 2 more reactive than SM can not stop at aldehyde

10 ' ester educing agent used: Al diisobutylaluminum hydride 簡稱 :DIBAL or DIBAL- or DIBA (soluble in org. solv. at low T) C 3 (C 2 ) 10 CEt DIBAL hexane 78 o C Al( i Bu) 2 C 3 (C 2 ) 10 C Et 2 C 3 (C 2 ) 10 88% C stops here at low T (Bu i ) 2 Al Et higher T or longer time C 3 (C 2 ) 10 C DIBAL C 3 (C 2 ) 10 C

11 C N nitrile 1) DIBAL 2) 2 Mechanism: C N Al( i Bu) 2 C N Al( i Bu) 2 2 C 2 + N 例 C 3 C=CC 2 C 2 C 2 CN 1) DIBAL hex. 78 o C 2) 2 + N 2 C 3 C=CC 2 C 2 C 2 C

12 Preparation of ketones xidation C ' Jones reagent ' zonolysis 1) 3 ' 2) Zn ' Friedel-Crafts acylation Ar- + Cl AlCl 3 Ar

13 Terminal acetylene methyl ketone g 2+ g 2+ g 2+ +, 2 2 C 3 gx + C 3 tautomerization

14 From nitrile C N + 'MgX (or 'Li) NMgX ' 3 + ' 例 C N 1) PhMgBr, ether 2) 3 + Ph

15 eactions of aldehydes and ketones Nucleophilic addition to the carbonyl δ δ + ' + -Nu Nu ' electrophilic eversibility depends on the nucleophile

16 Under basic conditions ' + Nu Nu ' Nu Nu ' + Nu In general: when the nucleophilic center is a heteroatom such as, N, S reversible if C irreversible (unless stabilized anion) 例 ' + "MgBr MgBr C " '

17 Acid catalyzed use a protic acid or a Lewis acid ' + ' Nu Nu ' + + ' Nu ' an oxonium ion reactivity is enhanced

18 Stereochemistry of the attack ' C LUM ' C Nu Nu ~109 o

19 xygen nucleophile ydrates + 2 C a hydrate or a gem-diol (gem for geminal) Mechanism: + 2

20 Catalyzed by acid Catalyzed by base + 2 +

21 The equilibrium constant C K eq 2.2 x C hydrates usually can not be isolated and exists only in solution 3 C C x 10 3 Ph C 3 δ Cl 3 C δ + C x x 10 4 stabilized by conjugation destabilized by EWG F 3 C CF 3 exists as: F 3 C C CF 3 this one is special

22 Kinetically aldehyde is also more reactive due to steric effect formaldehyde is extremely reactive in fact, it forms a trimer Electronically: aldehyde is also more reactive More electron donating group attached to carbonyl carbonyl carbon is less positive

23 emiacetals ( 半縮醛 ) + ' ' ' hemiacetal Catalyzed by acid and base emiacetals are unstable usually exist in solution Cyclic hemiacetals are more stable + a cyclic hemiacetal glucose exists in this form

24 Acetals ( 縮醛 ) ' + ' + ' ' + 2 verall: acetal ' + 2 " + " " ' + 2 Mechanism: ' + ' " " ' " ' " + " ' " " ' " 2 ' "

25 Acetals are stable and isolable Sensitive to acidic condition ' " " " ' also called as a hydrolysis ( 水解 ) reaction stable under basic condition used as carbonyl protecting group ( 保護基 ) ' ", + 2 protection ' " " 2, + ' deprotection

26 Cyclic acetals are often used as protecting groups +, + 2 ' ' an ethylene acetal Deprotection: ' +, 2 ' +

27 Mechanism: ' + ' ' 2 ' + + ' ' + '

28 例 Et + Et 1) LA, Et 2 2) 2 NaB 4, Et Et 2 +, 2

29 Nitrogen nucleophiles eactions with amines 3 C + 2 N-C 3 ether also called: Schiff base 2 3 C N C 3 an imine ( 亞胺 ) (acetaldimine) hydrolyzes back very easily

30 Mechanism: usually catalyzd by acid best performed at p ~3-4 3 C + 3 C N 2 C 3 3 C N 2 C 3 3 C NC C NC 3 an iminium ion 3 C 2 NC 3

31 xime and hydrazone + 2 N N + 2 例 3 C hydroxylamine + 2 N an oxime N 3 C + 2 acetaldoxime + 2 NN 2 NN hydrazine a hydrazone + NN 2 NNPh + 2 phenylhydrazine a phenylhydrazone

32 Formation of enamines N 4 5 a secondary amine + N an enamine Mechanism: N N

33 Carbon nucleophiles Addition of CN pk a ~9 ' + CN + CN ' CN CN cyanohydrins

34 Mechanism: CN CN + CN CN Applications: CN CN 95% 2 S 4 Cl 2 C 2 β C 3 C α C C 2 C 3 α,β-unsaturated acid CN CN 1) LA 2) 2 C 2 N 2

35 The Wittig reaction ' + Ph 3 P C '" phosphorous ylide (or phosphorane) " 'C=C"'" + Ph 3 P= triphenylphosphine oxide Preparation of the ylide ' Ph 3 P + X " X Ph 3 P C " ' Ph 3 P C " '" Ph 3 P C " '" base: n-buli or Na

36 Mechanism: + Ph 3 P ' C " C '" ' PPh 3 C " '" a betaine PPh 3 ' C C " '" an oxaphosphetane 'C=C"'" + Ph 3 P= 例 (E + Z) + Ph 3 P=C 2 C 2 + Ph 3 P 1) C 3 MgBr 2) 2 regiospecific C 3 +, 2 C 3 + C 2 a mixture is obtained non-regiospecific

37 Q: ow to prepare PhC C 3 C 3? PhC 2 Br Ph 3 P CPh + C 3 PhC C 3 C 3 C 3 Ph + Ph 3 P C 3 C 3 Br C 3 C 3

38 The orner-wadsworth-emmons modification of Wittig reaction base P Et Et a phosphonate ester M + P Et Et M + P Et Et + 84% + M + P Et Et *Preparation of phosphonate ester (Arbuzov reaction): X Et + P + EtX Et Et P Et Et triethyl phosphite

39 Mechanism of Arbuzov reaction: Br Br + Et Et P Et P Et Et EtBr + P Et Et

40 xidation Jones KMn 4, ; + Ag 2, ; +

41 eduction Clemmensen reduction Zn(g), Et Cl, 24 hr + 2 C 3 C 3 93% C 3 (C 2 ) 5 C Zn(g) 25% Cl C 3 (C 2 ) 5 C 3 87% *Zinc amalgam: a solution of zinc metal in g

42 or ' or ' LA NaB 4 /Et

43 More about prochirality 3 C Viewing from the top face: conuter-clockwise Si face Viewing from a different angle: The bottom face (backside of the screen): e face Si face 3 C e face

44 A simple chemical test for aldehyde Tollen s test (silver mirror test) + Ag(N 3 ) Ag silver mirror attached on test tube ' + Ag(N 3 ) 2 2 negative test (no reaction) but: ' Ag(N 3 ) ' + Ag α-hydroxy ketone

45 Spectroscopy I: C= stretching ' ' This form has higher contribution in ketones has more single bond character (less reactive) (~1730) (~1715)

46 Conjugation effect: Ar (~1700) Ar (~1690) (~1700) (~1690) ing size effect: angle changes due to stretching smaller angle, higher strain, higher freq.

47 1 NM δ ~2 ppm δ ~9-10 ppm small J (~3 z) with α-hydrogens 13 C NM ' Ar ketone signal is weak

48 Mass α-cleavage ' M + M + 1 M + M + ' McLafferty rearrangement β α ' ' Cleavage of α,β-bond