Notes_CarbonylReactionsLecture

Notes_CarbonylReactionsLecture - Carbonyl Chemistry Survey...

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Unformatted text preview: Carbonyl Chemistry Survey of Reactions Lecture Supplements: pg. 4042 CFC, OWLS, PP: pg. 232256 Vollhardt: Chapter 17, SecEons 176, 177, 179 and 1711 Chapter 19, SecEon 199 to 1911 Chapter 20, SecEon 201 to 204 and 206 All materials herein are copyright 2008 Stephanie L. Gould. Materials are intended for personal use in conjuncEon with Chemistry 14D at UCLA. DistribuEon is not permiTed. Reactions 1) Hemiacetal/Hemiketal and Acetal/Ketal formaEon** 2) Imine formaEon** What is an imine? 3) Esters** FormaEon (Fischer EsterificaEon) Hydrolysis (ReacEon of Esters) 4) FormaEon of CC bonds** Grignard ReacEon Alkyne Anion ReacEon 5) Metal Hydride ReacEons** **Mechanisms covered in this secEon (you should know these!) Copyright 2008 Stephanie L. Gould Aldehyde + Alcohol Hemiacetal Acetal O C R H R'OH HO R OR' H R'OH R'O R OR' H Ketone + Alcohol Hemiketal Ketal O C R R' R R' R R' R''OH HO OR'' R''OH R''O OR'' CatalyEc H+ is necessary why? Copyright 2008 Stephanie L. Gould Hemiacetal/Hemiketal Formation O C R H HO R OR' H R'OH H+ H OH C R R'OH Solvent or Conjugate Base HO H OR' H R Copyright 2008 Stephanie L. Gould Acetal/Ketal Formation H+ HO R OR' H R'OH H+ R'O R OR' H Solvent or Conjugate Base H H2O R OR' H OR C R H + H2O R'O R OR' H R'OH Copyright 2008 Stephanie L. Gould Biologically Important? YES! O H HO H H H OH H OH OH CH2OH D-Glucose HO H OH OH OH OH O D-Glucose H OH H O HO HO H H H OH OH H2O H OH H OH HO HO H H H OH O H2O H OH H O HO HO H H OH OH H -D-Glucose -D-Glucose Forms interconvert over a Eme scale of hours in water Copyright 2008 Stephanie L. Gould Equilibrium RaEo: 36:64 (:) End of Lecture 1 Start of Lecture 2 Exam Information Rooms: La Kretz 110 Last Names AM Franz 1178 Last Names NZ Wednesday, May 28th, 57pm Copyright 2008 Stephanie L. Gould Generalized C=O Reactions O If X is an LG Nuc Nucleophilic Carbonyl Substitution O X Nuc O X Nuc If X is not an LG HO X Addition Nuc Copyright 2008 Stephanie L. Gould X=LG O C R O H R O C Cl R O C H XLG O C R R O C R O C R O R O O C R' O C R N R'' R' O C R S Copyright 2008 Stephanie L. Gould R Biologically Important? YES! H OH H O HO HO H H H OH OH H2O HO HO H H H OH H OH H OH O H2O H OH H O HO HO H H OH OH H -D-Glucose -D-Glucose OH H C O H+ C OH OH H C O H OH H H2O C O H OH Copyright 2008 Stephanie L. Gould Reactions 1) Hemiacetal/Hemiketal and Acetal/Ketal formaEon** 2) Imine formaEon** What is an imine? 3) Esters** FormaEon (Fischer EsterificaEon) Hydrolysis (ReacEon of Esters) 4) FormaEon of CC bonds** Grignard ReacEon Alkyne Anion ReacEon 5) Metal Hydride ReacEons** **Mechanisms covered in this secEon (you should know these!) Copyright 2008 Stephanie L. Gould Imine Formation Aldehyde/Ketone + Primary Amine Imine O C R R' R R'' R''NH2 N C R' Imine is a compound with the C=N bond Requires small amount of catalyEc H+ Copyright 2008 Stephanie L. Gould Imine Formation Mechanism H+ H O R''NH2 C R R' R H2O NH R'' R' O H2N R' R'' HO R H+ H N R R' R'' H2O HN R R' R'' HO HN R R' R'' aminol intermediate H2O H N R R'' N C R R'' R' R' Copyright 2008 Stephanie L. Gould Rhodopsin and Vision H3C H O CH3 H3C CH3 Protein Protein-NH2 H3O+ Protein=Opsin N H CH3 H3C H3C CH3 CH3 CH3 retinal rhodopsin Rhodopsin is a key part of your rod pigments as apart of the vision cycle Imine formaEon results in a key bond between cofactor (reEnal) and protein (opsin) Copyright 2008 Stephanie L. Gould Properties of Imines 1) Nucleophilic ATack O C R'' N C R' R R' Smaller magnitude of dipole R C=N Less reacEve than C=O to nucleophilic aTack 2) Electrophilic ATack N less electronegaEve than O Imine lone pair more reacEve to electrophilic reacEons 3) Enolate FormaEon Number of resonance structures the same N less electronegaEve Imine less likely to form enolate (needs strong base) Copyright 2008 Stephanie L. Gould Reactions 1) Hemiacetal/Hemiketal and Acetal/Ketal formaEon** 2) Imine formaEon** What is an imine? 3) Esters** FormaEon (Fischer EsterificaEon) Hydrolysis (ReacEon of Esters) 4) FormaEon of CC bonds** Grignard ReacEon Alkyne Anion ReacEon 5) Metal Hydride ReacEons** **Mechanisms covered in this secEon (you should know these!) Copyright 2008 Stephanie L. Gould Formation of an Ester (Esterification) Carboxylic Acid + Alcohol Ester O C R O H R'OH No RXN Copyright 2008 Stephanie L. Gould Carboxylic Acid + Alcohol + H3O+ Ester O C R O H vs R OH C O H O C R O H R'OH H+ (Strong Acid) R O C O R' Emil Fischer Nobel Prize 1902 Acid cat EsterificaEon 1895 Fischer ProjecEons 1891 Fischer EsterificaEon hTp://nobelprize.org/nobel_prizes/chemistry/laureates/1902/fischerbio.html Copyright 2008 Stephanie L. Gould Fischer Esterification Mechanism H O R' H + H+ O R' H O C R O H R OH C O H H O H H H O R OR' R' O R' H2O R O OH R' HO R O OH R' HO HO R OH R' R' O H H O R' O H O C R OR' Copyright 2008 Stephanie L. Gould R OR' Practice Problem - Mechanism O OH + H2SO4 HO O Isopentyl Acetate Pear Flavoring O Copyright 2008 Stephanie L. Gould O OH + H2SO4 HO H+ O O Isopentyl Acetate Pear Flavoring H OH C H2O OH O H OH O HO HO H O H H O O H2O O OH HO O OH O H H O O O Copyright 2008 Stephanie L. Gould O Ester Hydrolysis with a Base O O O NaOH H2O 2 O O O OH O O O + O O OH HO- O O O R' R O NaOH H2O O + OH R' O H Copyright 2008 Stephanie L. Gould End of Lecture 2 Start of Lecture 3 Exam Information Rooms: La Kretz 110 Last Names AM Franz 1178 Last Names NZ Wednesday, May 28th, 57pm Material Weeks 58 Do NOT use red pen on your exam Copyright 2008 Stephanie L. Gould Ester Hydrolysis with a Base O R' R HO- NaOH O H2O R O + OH R' O H -O OR' OH O + OR' O- Rxn Workup R O + OH R' O H R Copyright 2008 Stephanie L. Gould Reactions 1) Hemiacetal/Hemiketal and Acetal/Ketal formaEon** 2) Imine formaEon** What is an imine? 3) Esters** FormaEon (Fischer EsterificaEon) Hydrolysis (ReacEon of Esters) 4) FormaEon of CC bonds** Grignard ReacEon Alkyne Anion ReacEon 5) Metal Hydride ReacEons** **Mechanisms covered in this secEon (you should know these!) Copyright 2008 Stephanie L. Gould Grignard Reaction Forming a CC bond from a Carbonyl: R R' R'' + X O C R' R Mg Ether, rt R R' R'' MgX Franois Auguste Victor Grignard Nobel Prize 1912 Form with Methyl, 1, 2 or 3 alkyl halides R R' R'' C + R R' R'' Carbanion Copyright 2008 Stephanie L. Gould MgX C MgX hTp://nobelprize.org/nobel_prizes/chemistry/laureates/1912/grignard Using a Grignard Reagent Ketone + Grignard Reagent gives rise to a terEary alcohol product Mg H3C Br Ether, rt H3C MgBr + R O C R BrMg R O CH3 H+ R HO R CH3 R H3C Br 1. Mg 2. Ketone 3. H3O+ HO R CH3 R Copyright 2008 Stephanie L. Gould Using a Grignard Reagent Aldehyde + Grignard Reagent gives rise to a secondary alcohol product* Mg H3C Br Ether, rt H3C MgBr O + R C H R H R H BrMg O CH3 H+ HO CH3 H3C Br 1. Mg 2. Aldehyde 3. H3O+ HO R CH3 H Copyright 2008 Stephanie L. Gould *Primary alcohol when formaldehyde is the carbonyl reagent Using a Grignard Reagent Esters/Amide/Anhydride/Acid Chloride + Grignard Reagent gives rise to a terEary alcohol product (subsEtuEon then second addiEon) Mg Br Ether, rt MgBr O + R C OCH3 BrMg R O OCH3 O HO R H+ BrMg R Copyright 2008 Stephanie L. Gould O MgBr R What is the major product? O C Cl 1. CH3CH2CH2MgBr (excess) 2. H3O+ HO Cl 1. Mg 2. CH3COCH3 3. H3O+ 1. Mg 2. H2CO I 3. H3O+ C H2 OH Copyright 2008 Stephanie L. Gould Addition of Alkyne Anions R C C H NaNH2 R C C H has a pKa of 25 More acidic than CH bond in CH4 Can be removed with a strong base O C R R R R' O R H+ HO R R R' R' C C Copyright 2008 Stephanie L. Gould Worksheet Problems QuesEons included for this midterm: b, d, e, g, h, I, j O CH3 CH3CH2OH (excess) Cat. H+ CH3 O O b) O Cat. H+ d) H2N N Copyright 2008 Stephanie L. Gould Worksheet Problems e) O H OH O g) H3C C C Na O 1. CH2CHCH2CH2MgBr 2. H3O+ O THF CH3 h) Br 1. Mg, THF 2. H2CO 3. H3O+ OH Copyright 2008 Stephanie L. Gould End of Lecture 3 Start of Lecture 4 Reactions 1) Hemiacetal/Hemiketal and Acetal/Ketal formaEon** 2) Imine formaEon** What is an imine? 3) Esters** FormaEon (Fischer EsterificaEon) Hydrolysis (ReacEon of Esters) 4) FormaEon of CC bonds** Grignard ReacEon Alkyne Anion ReacEon 5) Metal Hydride ReacEons** **Mechanisms covered in this secEon (you should know these!) Copyright 2008 Stephanie L. Gould Metal Hydride Reactions O C R R 1. HR O R H 2. H+ HO R R H Hydride (H:) Common Hydride Sources: NaBH4 or LiAlH4 O C R O C R H R 1. LiAlH4 or NaBH4 2. H3O+ 1. LiAlH4 or NaBH4 3 Copyright 2008 Stephanie L. Gould HO R HO R R H H H Ketones give 2 Alcohols Aldehydes give 1 Alcohol 2. H O+ Mechansim for H:- Addition to C=O O OH 1. LiAlH4 THF 2. H3O+ H H Li+ Al H3 O H H+ Copyright 2008 Stephanie L. Gould Properties of Hydrides LiAlH4 Solvent NaBH4 Ethers Ethanol, Aq. Ethanol Et2O or THF Dilute Base <20% NaOH Avoid ProEc, Halogenated, Avoid Acids and Acid Solvents Ketone, Aldehyde Ester, Anhydride, Reacts With Carboxylic Acid, (and many other funcEonal grps) Products 1 and 2 Alcohols Copyright 2008 Stephanie L. Gould Ketone, Aldehyde 1 and 2 Alcohols Metal Hydride Reactions O C R O C R O C R O R 1. LiAlH4 or NaBH4 R 2. H3O+ 1. LiAlH4 or NaBH4 H 2. H3O+ 1. LiAlH4 2. H3O+ HO R HO R HO R H R H H H H O C R N R'' R' 1. LiAlH4 2. H3O+ R H H N R2 R1 Copyright 2008 Stephanie L. Gould What is the major product? O 1. LiAlH4 O 2. H3O+ OH H H + OH O C 1. NaBH4 2. H3O+ HO H O C NH 1. LiAlH4 2. H3 O+ H H NH O C N 1. NaBH4 2. H3 O+ No Rxn Copyright 2008 Stephanie L. Gould Presence of Acid Catalysis with C=O O If X is an LG O X Nuc O X Nuc If X is not an LG Nuc Nucleophilic Carbonyl Substitution HO X Addition Nuc O X H+ OH C X OH C X Nuc Copyright 2008 Stephanie L. Gould Presence of Base Catalysis with C=O O If X is an LG O X Nuc O X Nuc If X is not an LG Nuc Nucleophilic Carbonyl Substitution HO X Addition Nuc Base H Nuc Nuc Copyright 2008 Stephanie L. Gould Enzymes in Biological Systems Enzymes are the biological "Catalyst" Can hance rates as much as 1028 vs noncatalyzed reacEons How enzymes increase rate: 1) Organize Reactants in the correct orienaEon 2) Stabilize the transiEon state Copyright 2008 Stephanie L. Gould Copyright 2008 Stephanie L. Gould Hardinger Lecture Supplement pg. 42 Worksheet Problems Now you can complete parts a, c, f Copyright 2008 Stephanie L. Gould ...
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