Topic 3 Aldehydes and Ketones

Transcription

1 3-1 Topic 3 Aldehydes and Ketones Aldehydes and Ketones ' aldehyde ketone The polarized oxygen-carbon -bond renders aldehydes and ketones electrophilic: ' The electrophilicity of the oxygen-carbon -bond can be further increased by protonation of the carbonyl oxygen lone pair: CEM 2312 Spring 2017 Notes: C.J. ahrni

2 3-3 Electrophilicity Based on M Theory C C C Due to the higher electronegativity of oxygen compared to carbon, the LUM energy of a C= bond is lower compared to a non-polar C=C bond. This renders the C= bond electrophilic Nomenclature Aldehydes: methanal formaldehyde ethanal acetaldehyde propanal propionaldehdye alkane => alkanal Example: Ketones: butanone ethyl methyl ketone 2-pentanone methyl propyl ketone pent-4-en-2-one allyl methyl ketone ' alkane => #-alkanone alkyl alkyl ketone Example: CEM 2312 Spring 2017 Notes: C.J. ahrni

3 Physical Properties The carbonyl group is has a permanent dipole moment; therefore, aldehydes and ketones have higher boiling points than hydrocarbons of the same molecular weight: butane propanal acetone 1-propanol Boiling point Molecular weight 0.5 C C C C xidation and eduction of Carbonyl Compounds xidation: increase of the formal oxidation number eduction: decrease of the formal oxidation number [ox] [ox] [ox] [red] [red] [red] CEM 2312 Spring 2017 Notes: C.J. ahrni

4 xidation of Alcohols eagent: Na 2 Cr 2 7, 2 S 4, 2 (or 2 Cr 4 ) Primary Alcohols: [ox] Secondary Alcohols: [ox] ' Tertiary Alcohols: " ' [ox] 3-8 Problem: Write the reaction product(s) for the following conversions: 1. KMn 4, K, Na 2 Cr 2 7, 2 S 4 2 Na 2 Cr 2 7, 2 S 4 2 CEM 2312 Spring 2017 Notes: C.J. ahrni

5 xidation of Alcohols: Mild xidants Primary Alcohols: [ox] PCC C 2 Cl 2 PCC = pyridinium chlorochromate N Cr 3 Cl xidation of Aldehydes 1. KMn 4, K, Na 2 Cr 2 7, 2 S 4 2 Ag 2, Na 2 AgN 3, N 3 Na, 2 CEM 2312 Spring 2017 Notes: C.J. ahrni

6 xidation of Ketones: Baeyer-Villiger eaction C 3 C 3 Mechanism: Migratory aptitude: Ph > 3 > 2 > 1 > Me 3-12 Problem: Write the reaction product(s) for the following conversions: C 3 C 3 1. KMn 4, K, heat 2. 3 CEM 2312 Spring 2017 Notes: C.J. ahrni

7 eduction of Carboxylic Acid Derivatives ' [red] [red] 1. LiAl LiAl Note: NaB 4 is a milder reducing agent and does not reduce carboxylic acids or esters 16.4C 3-14 eduction of carboxylic acid derivatives with sterically hindered reducing agents: Cl LiAl(t-Bu) 3 78 C t Bu Al t Bu t Bu Li C 3 DIBAL- 78 C Al C N DIBAL- 78 C CEM 2312 Spring 2017 Notes: C.J. ahrni

8 eduction of Aldehydes and Ketones [red] NaB 4 reduces both aldehydes and ketones to the corresponding alcohols: 1. LiAl 4 or NaB LiAl 4 or NaB verview Br Cl CEM 2312 Spring 2017 Notes: C.J. ahrni

9 12.4C/D Alkenes: Chemical Tests for unctional Groups Alkenes decolorize bromine through a 1,2-addition reaction Br 2 in CCl 3 alkene brown solution colorless 2. Primary and secondary alcohols: The Jones eagent orange solution blue solution Na 2 Cr 2 7, 2 S 4 1 or 2 alcohol ' 2 ' 16.13B Tollen s Test for Aldehydes: Aldehydes reduce Ag(I) to Ag(0) which forms a silver mirror: colorless solution silver mirror aldehyde AgN 3, N 3 Na, 2 carboxylic acid CEM 2312 Spring 2017 Notes: C.J. ahrni

10 xidation of primary alcohols: Synthesis of Aldehydes PCC C 2 Cl 2 2. eduction of carboxylic acid derivatives: 1) DIBAL-, 78 C C 3 2) 2 Cl C 3 1) LiAl(t-Bu) 3, 78 C 2) 2 1) DIBAL-, 78 C 2) 2 C N 1) DIBAL-, 78 C 2) xidation of secondary alcohols: Synthesis of Ketones KMn 4, 2 S 4 2 or: 2. zonolysis of alkenes: Zn, Ac 3. ydration of alkynes: gs 4 2 S 4 4. riedel-crafts acylation: C 3 C3 CCl AlCl 3 CEM 2312 Spring 2017 Notes: C.J. ahrni

11 Problem: Provide a synthesis of 3-hexanone from starting materials with three or fewer carbon atoms Problem: Provide a synthesis of cyclohexanone starting from cyclohexane CEM 2312 Spring 2017 Notes: C.J. ahrni

12 16.6; 12.1A 3-23 Nucleophilic Addition to the C= Double Bond General eaction 1 2 Nu Examples: CN 16.6; 12.1A 3-24 xygen Nucleophiles: Addition of Water and Alcohols 1. Addition of Water: ' ' hydrate 2. Addition of Alcohols: ormation of emiacetals and Acetals ' ' hemiacetal ' hemiacetal ' ' ' acetal 2 CEM 2312 Spring 2017 Notes: C.J. ahrni

13 Mechanism for the Acid Catalyzed ormation of ydrates: Mechanism for the Base Catalyzed ormation of ydrates: CEM 2312 Spring 2017 Notes: C.J. ahrni

14 Thermodynamics of ydrate ormation ' K eq ' hydrate ' K eq % hydrate C x C(C 3 ) x C 3 C x C 3 C 3 22, Electronic actors: Electron donating substituents stabilize the carbonyl group and yield a less favorable G for hydrate formation (and vice versa): ' C 3 C 3 Steric actors: Bulky groups destabilize the hydrae product due to steric crowding: ' ' sp 2 sp 3 CEM 2312 Spring 2017 Notes: C.J. ahrni

15 emiacetals Acid-Catalyzed ormation of emiacetals: Base-Catalyzed ormation of emiacetals: ' 3-30 Problem: Most simple sugars exist primarily in a cyclic hemiacetal form. Draw the open chain structure (aldehyde form) for ()-glucose shown below. ()-Glucose CEM 2312 Spring 2017 Notes: C.J. ahrni

16 16.7B 3-31 Acetals Acetals are only formed under acid-catalyzed conditions: ' ' hemiacetal Why doesn t this reaction proceed under basic conditions? 16.7B 3-32 All steps in the formation of an acetal from an aldehyde (or ketone) are reversible. In excess water, acetals undergo acid-catalyzed hydrolysis: cyclic acetal Microscopic reversibility: orward and back reactions take place via the same transition states and intermediates. CEM 2312 Spring 2017 Notes: C.J. ahrni

17 16.7C 3-33 Acetals as Protecting Groups Although acetals are hdyrolyzed to aldehydes (or ketones) in aqueous acid, they are stable in basic solution => This offers a convenient method from undesired reactions under basic conditions Example: eduction of an ester to an alcohol in the presence of a ketone Et? Et 1. LiAl Problem: Shown below is the structural formula for sucrose (table sugar). Identify the acetal group(s) in this molecule Sucrose CEM 2312 Spring 2017 Notes: C.J. ahrni

18 Problem (16.44): Dutch elm disease is caused by a fungus transmitted to elm trees by the bark beetle. The female beetle releases several hormones, including multistriatin, which attract male beetles carrying the deadly fungus. Treating multistriatin with dilute acid at room temperature leads to formation of a product, C , which shows a strong infrared peak near 1715 cm 1. Propose a structure for this product multistriatin 16.8A 3-36 Nitrogen Nucleophiles: Addition-Elimination 1. Addition of a primary amine: N ' ' N 2 imine 2 Mechanism: 2 N CEM 2312 Spring 2017 Notes: C.J. ahrni

19 16.8D Addition of a secondary amine: ' N ' ' ' N enamine 2 Mechanism: N 16.8B 3-38 eactions with other Ammonia Derivatives 1. Addition of hydroxylamine: 2 N hydroxylamine N oxime 2 2. Addition of hydrazine: N N 2 2 N N 2 hydrazine hydrazone 2 2 N NN 2 N 2 2 N N N N 2 2 2,4-dinitrophenyl hydrazine 2,4-dinitrophenylhydrazone CEM 2312 Spring 2017 Notes: C.J. ahrni

20 16.8C 3-39 Wolff-Kishner eduction 2 N N 2 K heat benzophenone diphenylmethane Mechanism: Ph Ph N 2 N N 2 Ph Ph N 16.9, Addition of hydrogen cyanide: Carbon Nucleophiles CN CN hydrogen cyanide cyanohydrine 2. Addition of organometallic compounds: 1. ' M M ' 2. 2 ' Ph 1. C 3 -Li 2. 2 Ph C 3 CEM 2312 Spring 2017 Notes: C.J. ahrni

21 rganometallic Compounds rel. orbital energy LUM M C Br C C C Li The nucleophilicity of organometallic compounds depends on the electronegativity of the metal: CEM 2312 Spring 2017 Li C C Na MgX 1.2 ZnX 1.7 2CuLi 1.8 Notes: C.J. ahrni

22 rganolithium and rganomagnesium Compounds Preparation: alogen-metal Exchange X 2 Li Li LiX X Mg X Zn eactivity: I > Br > Cl >> Solvent is usually Et 2 or tetrahydrofuran (T) eactivity of Li and MgX eagents 1. Addition to Carbonyl Groups: 1. 3 C MgBr Ph 2. 2 MgCl Ph 1. Ph Li Ph 2. 2 Na CEM 2312 Spring 2017 Notes: C.J. ahrni

23 12.7B ingopening of epoxides: C 3 1. Ph MgCl 2. 2 C C 2. 2 Li 3. Grignard (MgX) and Lithium eagents as Bases: 3 C MgBr 3 C MgBr 3 C Li 3 C Li C 3 Note: MgX and Li react with alkylhalides via E2 elimination rather than SN2 substitution 3-46 Problem: Identify the structures of compounds A-E in the following scheme: 2 Cr 4 acetone A 1. C 3 MgBr 2. 2 B 2 S 4 C 6 10 C 7 14 C 1. 3 D 2. Zn, Ac 1. Ag 2, Na 2. 3 E C 7 12 C C CEM 2312 Spring 2017 Notes: C.J. ahrni

24 12.8A 3-47 Designing Syntheses with Li and MgX eagents Target: Ph C 3 etrosynthetic analysis: Ph C 3 Ph Ph C 3 3 C Ph C 3 Ph C 3 Problem: Propose a synthesis of 2-methyl-2-hexanol from starting materials with four or fewer carbon atoms CEM 2312 Spring 2017 Notes: C.J. ahrni

25 3-49 Problem: Starting from benzene, propose a synthesis of the following aldehyde: 12.8B 3-50 estrictions on the Use of Li and MgX eagents Mg X MgX ether Grignard and lithium organic reagents are very strong nucleophiles and bases. or this reason, Grignard reagents containing the following functional groups cannot be prepared: functional groups with lower pka N 2 C 2 S 3 S C C CN 2 electrophiles ' N 2 CN CEM 2312 Spring 2017 Notes: C.J. ahrni

26 3-51 Similarly, the electrophile used for the Grignard reaction cannot contain any of the functional groups listed on the previous slide. Example: C 3 MgBr 3-52 Protecting Groups in Grignard Syntheses Example: ow would you achieve the following transformation? Br CEM 2312 Spring 2017 Notes: C.J. ahrni

27 rganozinc Compounds: The eformatsky eaction 3-53 rganozinc reagents are less nucleophilic than Grignard and lithium reagents. While they still undergo addition to aldehydes and ketones, the less electrophilic esters do not react. Example: Br Et Zn, benzene ZnBr Et 1. PhC 2. 2 Sergey N. eformatsky Problem: Propose a multistep synthesis for the following conversion: Me Me CEM 2312 Spring 2017 Notes: C.J. ahrni

28 Special Topic: G Lithium Dialkylcuprates Lithium dialkylcuprates are much less basic than Grignard or organolithium reagents but still suf ciently nucleophilic to undergo substitution reactions: Example: C 3 Li Br Br (C 3 ) 2 CuLi Preparation: 3 C Br 2 Li 3 C Li LiBr 3 C Li CuI 2 3 C Cu C 3 Li 3-56 Substitution eactions at sp 2 carbon centers (Corey-ouse synthesis): vinyl halides Br Et 2 CuLi aryl halides I Bu 2 CuLi CEM 2312 Spring 2017 Notes: C.J. ahrni

29 16.10 Addition of Ylides to Aldehydes and Ketones: The Wittig eaction 3-57 Wittig eaction: PPh 3 Br 1 2 PPh 3 Br 2. BuLi 1 2 PPh 3 LiBr phosphonium ylide 1 2 PPh Georg Wittig Mechanism: 1 2 PPh CEM 2312 Spring 2017 Notes: C.J. ahrni

30 16.10B 3-59 Alternate Method: Use of a phosphonate ester (orner-wadsworth-emmons eaction) P Et Et Na P Et Et Na phosphonate ester P Et Et Na 16.10A 3-60 Designing Syntheses with the Wittig eaction Target: etrosynthetic analysis: PPh 3 Ph 3 P CEM 2312 Spring 2017 Notes: C.J. ahrni

31 3-61 Problem: The following structure is an intermediate in the synthesis of prostaglandins. Write structures for the phosphonate ester and carbonyl reactant that were used to form this (E)-alkene. Ac Spectroscopic Properties of Aldehydes and Ketones Problem: Propose a structure for compound A based on the following data: The compound contains C,, Br, and M = 184 and 186 Positive Tollen s test I 1690 cm 1 1 NM: singlet at 10.1 ppm, doublets at 8.1 and 7.5 ppm CEM 2312 Spring 2017 Notes: C.J. ahrni

32 3-63 Problem: Propose a structure for compound B based on the following data: CEM 2312 Spring 2017 Notes: C.J. ahrni