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To explain 1H-NMR is based on four informations: ☺Integration: ratio of H atoms ☺Chemical shift: chemical environment ☺Spin-spin coupling: information about neighboring nuclei ☺Coupling constant: isomers (cis or trans)

有機化學祕笈 陳清玉

當你會draw bond line後，仍無法清楚描繪結構 ↓ 共振，clouds of electron density 1.畫共振結構的工具是彎曲箭 (指電子流動的方向) ․不能break single bond ․不可違背Octet rule 2.共振結構中的形式電荷 (共用電子對可以不用畫) 3.應stepwise畫共振結構

有5種模式常用來畫共振 緊鄰p鍵的lone pair 2.緊鄰cation的lone pair 3.緊鄰cation的p鍵 4. 2個原子間的p鍵，其中一個原子electronegativity高 (This is better to have examples)

5.環繞整個環的p鍵 ↓ 估計共振結構的相對重要性

follows some rules: 1.電荷越少越好 2.負電荷需位於陰電性高的原子上 3.有些情形，其中的正電荷在陰電性原子上(先決條件合乎八隅體法則)

Acid – Base 前面幾章都是在說明分子結構的一切，但有一種反應例外，就是酸鹼化 學。為何不在後面再來談酸鹼化學? 要搞清楚酸鹼化學並不難，有一項技術: 面對負電荷時，要能看出它有 多穩定。 ↓ 先教是因電荷穩定度是了解分子結構不可或缺的部份 ∴4個重要因素來判斷那類電荷穩定，哪類電荷不穩定

電荷放在哪個原子上？ ․陰電性 ․大小 例： C- < F- (陰電性important) I- > F- (大小important)

2.共振 (resonance) 例： 3.感應 (inductive)

4.軌域 (orbital) More s character, more electronegative sp3, sp2, sp are similar outlook, but size different 上述的4個因素之重要性依次遞減：1 > 2 > 3 > 4

↓ 測量酸性pka值 (定量) 前面都是在討論定性方面，也就是相對的酸性，現在要來看定量 pka 4 is acidic than pka 7 for 1000 times 預估平衡位置 (equilibrium) A-/B- 兩個化合物的質子(H+)爭奪戰

分子幾何學 本章要教你無須思考就能對化合物的幾何結構了然於胸 ☻各種軌域與混成狀態 ☻幾何學 了解如何決定混成狀態，下一步要知道三種不同的混合狀態， 各有怎樣的幾何結構 ↓ valence shell electron pair repulsion theory, VSEPR 簡單地說，所有含有外層電子的軌域，要盡可能互相遠離

構形 conformation 由同一個分子所擺出來的種種不同姿勢稱為構形 姿勢有能量高低 例: 倒立無法喝水 跑步得先站起來 藉由了解分子構形能量高低，才能判斷某種反應是否會發生 有兩種結構畫法來幫助我們預測分子的構形 ․Newman projection ․chair conformation

組態 configuration 左臂、右臂切下來不能互相交換，∴一個分子在3D的空間內， 我們來選用R/S表示兩種可能 構形指分子透過rotation呈現不同姿勢，但組態則指左手型或右手型 ☻找出立體中心的位置 stereoisomer: enantiomer, diastereomer ☻光學活性 R/S: 人設立方便測量 +/-: 平面偏極光穿過化合物時，偏光的平面會發生旋轉，+表示順時鐘方向 旋轉，-表示逆時鐘方向旋轉，+/-是測量到的物理效應，而且+/-的數值與溫 度有密切關係所以，我們可以決定R/S，但不能預測+/-

mechanism ☻反應機構記錄電子的流動 未共用電子對attack bond 2. bond attack lone pair 3. bond attack bond 4. lone pair attack lone pair

☻ 鹼槓上了親核基 (basicity / nucleophilicity) nucleophilicity: 反應速度 (快∕慢)(kinetic control) basicity: 指平衡的位置(thermodynamic control) ☻ 反應機構內包含了區域選擇性 (regiochemistry) Elimination: Zaitsev product; Hoffmann product Addition: Markovnikov product; anti-Markovnikov product ☻ 反應機構內包含了立體化學 (stereoselective) Syn-addition and anti-addition ☻ 反應機構清單

․Second-Row Nucleophiles in the SN2 Reaction Basicity－ measure of a compound shared its lone pair 可經由equilibrium constant （acid dissociation constant Ka）strong / weak Nucleophilicity － measure of a compound is able to attack an electron－deficient atom可經由rate constant (K) 來得知 good / poor RULE 1 (Second-row) nucleophiles: Are approximately the same size. The stronger the base, the better the nucleophile. stronger base, better nucleophile weaker base, poorer nucleophile OH– > H2O CH3O– > CH3OH H2N– > NH3 CH3CH2NH– > CH3CH2NH2 19

RULE 2 attacking atoms are very different in size 則要考慮Polarizability Higher-Row Nucleophiles in the SN2 Reaction Down a column of the periodic table: nucleophiles become larger and more polarizable, but less solvated and less basic. Polarizability means that the loosely held electron cloud of iodide is readily distorted The tightly held electron cloud of fluoride is less polarizable. 20

Substitution ☻Effect 1, E+ electrophile (substrate, 受質) ☻Mechanism In organic chemistry, 95% belong to Nu- + E+ reactions (SN1 and SN2) ☻Effect 1, E+ electrophile (substrate, 受質) 因為mechanism不同，其rate-determining的因素不同 ☻Effect 2, Nu- nucleophile

☻Effect 3, Leaving group 若受質substrate 20 , 而Nu-溫和，則SN1? SN2? ․Extremely good leaving group: (中性) ․Good leaving group, stable anion: ․Bad leaving group: RO-, R2N-

分類of leaving group (stability): neutral > stable anion > unstable anion 其中leaving group對SN1 and SN2影響各有不同 ∴SN1對leaving group的要求較SN2敏感

☻Effect 4, Solvent SN2: we need polar aprotic solvent (acetone, DMSO, DME, DMF), 不會stabilize Nu- ∴good for reaction 當上述的4個因素互相牴觸時，我們得逐一衡量它們各自的影響力， 找出誰能壓倒其他因素，操控反應的進行與走向。 整個化學中多半可由steric / electronic來解釋. (electronic effect, eg. Substrate, leaving group, solvent effect etc…)

Elimination 與SN1 and SN2 的concept similar ․Effect 1: Substrate ․Effect 2: Base

Here, we should talk about Nu- / Base 得強弱 ∵Nu-屬於kinetic attack (eg. S- is better Nu- than O-, ∵S-會極化∴induce電子密度) base 屬於thermodynamic attack

․Effect 3: Leaving group E1 is more sensitive to the tendency of the leaving group ․Effect 4: Solvent effect polar aprotic solvent (acetone, DMSO, DME, DMF) ☻Regiochemistry, Stereochemistry For the regiochemistry, There are two different products, one is Zaitsev product, the other is Hoffmann product For stereochemistry, you need to know the elimination mechanism are syn-elimination or anti-elimination. You can use Newman project technique.

Addition reaction 加成反應要考慮Markovnikov addition or Anti-Markovnikov reaction ↓ regiochemistry, stereochemistry 先畫反應機構，要同時考慮regiochemistry and stereochemistry 這樣就會寫到right answer

預測產物 每回要決定產物為何時需3問個問題: ․發生的反應屬於那一類？ ․反應的regiochemistry為何？ ․反應的stereochemistry為何？