Chapter 19 Aldehydes and Ketones Organic Chemistry, 6 th Edition L. G. Wade, Jr.

Content Carbonyl Structure & Properties Preparation  Functional group transformations  Carbon-carbon bond formation  C-C Bond cleavage Reactions of Aldehydes and Ketones C=O  -H,  - C

Some Common Functional Groups: alkane alkene alkyne aromatic alcohol ether aldehyde ketoneacid esteramide amine carbonyl groups

Carbonyl Compounds

IUPAC Names for Ketones Replace -e with -one. Indicate the position of the carbonyl with a number. Number the chain so that carbonyl carbon has the lowest number. For cyclic ketones the carbonyl carbon is assigned the number 1. 3-bromocyclohexanone 4-hydroxy-3-methyl-2-butanone 4-hydroxy-3-methylbutan-2-one Examples

Naming Aldehydes IUPAC: Replace -e with -al. The aldehyde carbon is number 1. If -CHO is attached to a ring, use the suffix -carbaldehyde. Example 2-cyclopentenecarbaldehyde cyclopent-2-en-1-carbaldehyde

Name as Substituent On a molecule with a higher priority functional group, C=O is oxo- and -CHO is formyl. Aldehyde priority is higher than ketone. 3-methyl-4-oxopentanal 3-formylbenzoic acid

Common Names for Ketones Named as alkyl attachments to -C=O. Use Greek letters instead of numbers. Historical Common Names methyl isopropyl ketone  bromoethyl isopropyl ketone acetone acetophenone benzophenone

Aldehyde Common Names Use the common name of the acid. Drop -ic acid and add -aldehyde. 1 C: formic acid, formaldehyde 2 C ’ s: acetic acid, acetaldehyde 3 C ’ s: propionic acid, propionaldehyde 4 C ’ s: butyric acid, butyraldehyde.  -bromobutyraldehyde 3-bromobutanal

Sec 1 Structure & Properties Carbon is sp 2 hybridized. C=O bond is shorter, stronger, and more polar than C=C bond in alkenes. The carbonyl group is planar with bond angles of 120

Carbonyl Structure 丙酮 Electrostatic Potential Map Positively polarized carbon Negatively polarized oxygen The oxygen of the carbonyl group is a nucleophilic center. The carbonyl carbon is an electrophilic center

Boiling Points More polar, so higher boiling point than comparable alkane or ether. Cannot H-bond to each other, so lower boiling point than comparable alcohol.

Solubility Good solvent for alcohols. Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O-H or N-H. Low molecular weight aldehydes and ketones (e.g. formaldehyde and acetone) are soluble in water. large molecular weight aldehydes and ketones are insoluble in water. Aromatic ketones and aldehydes are insoluble in water due to the hydrophobic aromatic ring. Acetone and acetaldehyde are miscible in water.

Formaldehyde Gas at room temperature. Formalin is a 40% aqueous solution. trioxane, m.p. 62  C formaldehyde, b.p. -21  C formalin

Industrial Importance Acetone and methyl ethyl ketone are important solvents. Formaldehyde used in polymers like Bakelite . Flavorings and additives like vanilla, cinnamon, artificial butter. 胶木

人造奶油 香兰素 开心果 肉桂 樟脑 除虫菊酯 香芹 麝香酮 擦剂, 吸剂 香芹籽 薄荷 麝香香料

互变异构体 ， 酸碱对烯醇式都 有促进作用 Tautomers

睾丸激素 黄体酮 可的松

Some Aldehydes and Ketones cellulose glucose C 6 H 12 O 6 cellulose is a polymer of glucose honey 蜂蜜是过饱和溶液，低温产生葡萄糖结晶，不结晶部分主要是果糖。

Some Aldehydes and Ketones 雄 ( 甾 ) 烯二酮 雄甾酮

Some Aldehydes and Ketones:

Some Aldehydes and Ketones Oxycodone( 氧可酮, 羟氢可待因酮 )is an effective analgesic for mild to moderate pain control, chronic pain syndromes, and for the treatment of terminal cancer pain. Five mg of oxycodone is equivalent to 30 mg of codeine( 可待因 )when administered orally. Oxycodone and morphine are equipotent for pain control in the normal population; 10 mg of orally- administered oxycodone is equivalent to 10 mg of subcutaneously administered morphine.

Nonmedical OxycodoneUsers:Nonmedical OxycodoneUsers:

Sec 2 Preparation Functional group transformations Aldehydes can be synthesized by the oxidation of primary alcohols, or by the reduction of esters, acid chlorides, or nitriles. Ketones can be synthesized by the oxidation of secondary alcohols. Carbon-carbon bond formation C-C Bond cleavage

1. Functional group transformations Aldehydes can be synthesized by the oxidation of primary alcohols,or by the reduction of esters, acid chlorides, or nitriles. 二异丁基氢化铝

1. Functional group transformations Oxidation 2  alcohol + Na 2 Cr 2 O 7  ketone 1  alcohol + PCC  aldehyde 冰片 樟脑 樟树精油

1. Functional group transformations Hydration of terminal alkyne Use HgSO 4, H 2 SO 4, H 2 O for methyl ketone

2. carbon-carbon bond formation Ketones can be synthesized from the reaction of acid chlorides with organocuprate reagents, or from the reaction of nitriles with a Grignard or organolithium reagent. Aromatic ketones can be synthesized by the Friedel- Crafts acylation.

Ketones from Nitriles A Grignard or organolithium reagent attacks the nitrile carbon. The imine salt is then hydrolyzed to form a ketone.

Aldehydes from Acid Chlorides Use a mild reducing agent to prevent reduction to primary alcohol.

Ketones from Acid Chlorides Use lithium dialkylcuprate (R 2 CuLi), formed by the reaction of 2 moles of R-Li with cuprous iodide.

3.C-C Bond cleavage obtained from the ozonolysis of suitably substituted alkenes.

Show how you would synthesize each compound from starting materials containing no more than six carbon atoms. (a) (b) Solved Problem

An alternative route to the target compound involves Friedel– Crafts acylation. (a) This compound is a ketone with 12 carbon atoms. The carbon skeleton might be assembled from two six-carbon fragments using a Grignard reaction, which gives an alcohol that is easily oxidized to the target compound. Solution

Alternatively, we could construct the carbon skeleton using acetylene as the two-carbon fragment. The resulting terminal alkyne undergoes hydroboration to the correct aldehyde. Solution (Continued) (b) This compound is an aldehyde with eight carbon atoms. An aldehyde might come from oxidation of an alcohol (possibly a Grignard product) or hydroboration of an alkyne. If we use a Grignard, the restriction to six-carbon starting materials means we need to add two carbons to a methylcyclopentyl fragment, ending in a primary alcohol. Grignard addition to an epoxide does this. Di(secondary)isoamylborane, 双异戊基硼烷, [(CH3)2CHCH2CH2]2BH

结构特征： 1 、 C: Sp2 杂化 ; 共平面 2 、  - 电子强烈流向氧， C  + 3 、  -H 活性 4 、醛酮差异 (-H), 决定二者差异  +  - Structure & Reactivity α- 氢的反应 醛的反应

Sec 3 Nucleophilic Additions  Nucleophilic addition involves the addition of a nucleophile to an aldehyde or a ketone. Aldehydes are more reactive than ketones  The nucleophile adds to the electrophilic carbonyl carbon  Charged nucleophiles & Neutral nucleophiles

Charged nucleophiles  Charged nucleophiles : give a charged intermediate  Carbanion addition : Grignard reagents (RMgX) or organolithium reagents (RLi)  Hydride addition: H: -  Lithium aluminum hydride (LiAlH 4 )  Sodium borohydride (NaBH 4 )  Cyanide addition: CN -  Bisulfite addition:  Addition of enolate ions

羰基的加成－－－亲核加成 1

 Neutral nucleophiles require acid catalysis and further reactions can take place after nucleophilic addition

羰基的加成－－－亲核加成 2

1 、 Wittig Reaction Nucleophilic addition of phosphorus ylides. Product is alkene. C=O becomes C=C.

Phosphorus Ylides Prepared from triphenylphosphine and an unhindered alkyl halide. Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus.

Mechanism of the Wittig RX Oxaphosphetane formation Betaine formation The oxaphosphetane will collapse, forming carbonyl (ketone or aldehyde) and a molecule of triphenyl phosphine oxide.

2 、 Carbanion addition Grignard reagents (RMgX) or organolithium reagents (RLi)

与格氏试剂加成

 Lithium aluminum hydride (LiAlH 4 )  Sodium borohydride (NaBH 4 ) Mechanism tor the reaction of a ketone with H - Step 2 3 、 Hydride addition: H -

4 、 Cyanide addition Addition of HCN ： HCN is highly toxic. Use NaCN or KCN in base to add cyanide, then protonate to add H. Reactivity ： formaldehyde > aldehydes > ketones >> bulky ketones.

5 、 Nitrogen Nucleophiles Addition Imine( 亚胺 ) formation Enamine （烯胺） formation Oximes( 月亏 ),semicarbazones （缩氨基脲） and 2,4-dinitrophenylhydrazones （苯腙）

Formation of Imines Ammonia or a primary amine reacts with a ketone or an aldehyde to form an imine. Imines are nitrogen analogues of ketones and aldehydes with a C ═ N bond in place of the carbonyl group. Nucleophilic addition of ammonia or primary amine, followed by elimination of water molecule. Optimum pH is around 4.5

Mechanism of Imine Formation Acid-catalyzed addition of the amine to the carbonyl compound group. Acid-catalyzed dehydration.

月亏 亚胺 腙 苯腙 缩氨基脲 氨基脲 联氨，肼 苯肼 Other Condensations

苯甲醛 二苯甲酮苯腙 丙酮 -2,4- 二硝基苯腙 月亏

三聚氰胺（ Melamine ） 密胺、蛋白精

6 、 Oxygen and Sulfur Nucleophiles Addition of Water In acid, water is the nucleophile. In base, hydroxide is the nucleophile.

Hydration of Ketones and Aldehydes In an aqueous solution, a ketone or an aldehyde is in equilibrium with its hydrate, a geminal diol. With ketones, the equilibrium favors the unhydrated keto form (carbonyl).

Mechanism of Hydration of Ketones and Aldehydes Hydration occurs through the nucleophilic addition mechanism, with water (in acid) or hydroxide (in base) serving as the nucleophile.

Addition of Alcohol

Mechanism Must be acid-catalyzed. Adding H + to carbonyl makes it more reactive with weak nucleophile, ROH. Hemiacetal forms first, then acid-catalyzed loss of water, then addition of second molecule of ROH forms acetal. All steps are reversible.

Acetal and ketal formation

Acetals as Protecting Groups Sugars commonly exist as acetals or hemiacetals. Hydrolyze easily in acid, stable in base and neutrosphere. Aldehydes more reactive than ketones.

7 、 Bisulfite addition Aldehydes ， aliphatic methyl ketones and cycloketones(<8C) can react in this way. Application: Identify Purification

steric effects %

8 、 Electronic and steric effects  Reactivity  Steric factors  Electronic factor 影响反应的因素 ①空间因素 ②电子因素 ③亲核试剂的亲核性

Inductive effect of (a) trifluoroethanal; (b) ethanal.  反应性：醛 > 酮  R:+I C=O  空间障碍

羰基的加成－－－亲核加成 COMPARE CH 3 COCH 3, CH 3 CHO,HCHO,Cl 3 CCHO  Cl 3 CCHO> HCHO> CH 3 CHO> CH 3 COCH 3

Predict the products of the following reactions: ClCH 2 CHO + HCN CH 2 O + KCN H 2 SO 4

ClCH 2 CHO + HCN ClCH 2 CHCN(95%) OH CH 2 O + KCN HOCH 2 CN (80%) H 2 SO 4 85% 80% Predict the products of the following reactions:

Sec 4 Reduction and Oxidation  Reduction to alkanes  Reduction to alcohols  Oxidation  Aldehydes can be oxidized to carboxylic acids, but ketones are resistant to oxidation

①金属氢化物还原 1 、 Common Reduction Methods

②催化氢化

Sodium borohydride, NaBH 4, reduces C=O, but not C=C. Lithium aluminum hydride, LiAlH 4, much stronger, difficult to handle. Catalytic Hydrogenation ： Hydrogen gas with catalyst also reduces the C=C bond. Widely used in industry. Raney nickel, finely divided Ni powder saturated with hydrogen gas. Pt and Rh also used as catalysts.

Deoxygenation Reduction of C=O to CH 2 Two methods: Clemmensen reduction if molecule is stable in hot acid. Wolff-Kishner reduction if molecule is stable in very strong base.

2 、 C=O CH 2 ① Wolff-kishner 反应 Form hydrazone, then heat with strong base like KOH or potassium t-butoxide. Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMSO.

Wolff-Kisher Reduction

② Clemmensen 还原

Oxidation of Aldehydes Easily oxidized to carboxylic acids.

① Tollen Ag(NH 3 ) 2 + ② Fehllihg 试剂 Ⅰ.CuSO 4 /H 2 O Ⅱ. 酒石酸钾钠， NaOH /H 2 O ③ Benedict CuSO 4 ， Na 2 CO 3 ， 柠檬酸三钠 /H 2 O 用于鉴别醛和酮 用于鉴别醛和酮，例： 弱氧化剂

氧化规律 氧化性能依次降低 Tollens : 所有的醛都可以 Fehling : 只有脂肪醛可以 Benedict: 除甲醛外的脂肪醛 用途 : 鉴别 砖红色 银镜

不同烃基迁移速度由高到低的次序： Baeyer - V Villiger Reaction

5. Cannizzaro reaction 只有无 α-H 的醛，如 HCHO, R 3 CCHO, ArCHO 等才能发生康尼查罗反应 反应体系中有甲醛的话，甲醛发生氧化反应。

RXS

3º 醇 合成例 1: 2- 甲基 -1- 苯基 -2- 丁醇 酮 格氏试剂

酮 3º 醇 合成例 1: 2- 甲基 -1- 苯基 -2- 丁醇

3º 醇 酮 格氏试剂 合成例 1: 2- 甲基 -1- 苯基 -2- 丁醇 思路 2

酮 格氏试剂 3º 醇 合成例 1: 2- 甲基 -1- 苯基 -2- 丁醇 思路 2

3º 醇 酮 格氏试剂 合成例 1: 2- 甲基 -1- 苯基 -2- 丁醇 思路 3

Copyright© 1999, Michael J. Wovkulich. All rights reserved. 酮 格氏试剂 3º 醇 合成例 1: 2- 甲基 -1- 苯基 -2- 丁醇 思路 3

合成例 2

The End Of Chap ; 19-41; 19-42: (a),(d),(g); 19-47;