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Chapter 22 Alpha Substitution and Condensations of Enols and Enolate Ions Jo Blackburn Richland College, Dallas, TX Dallas County Community College District.

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Presentation on theme: "Chapter 22 Alpha Substitution and Condensations of Enols and Enolate Ions Jo Blackburn Richland College, Dallas, TX Dallas County Community College District."— Presentation transcript:

1 Chapter 22 Alpha Substitution and Condensations of Enols and Enolate Ions Jo Blackburn Richland College, Dallas, TX Dallas County Community College District  2006,  Prentice Hall Organic Chemistry, 6 th Edition L. G. Wade, Jr.

2 Chapter 222 Alpha Substitution Replacement of a hydrogen on the carbon adjacent to the carbonyl, C=O. =>

3 Chapter 223 Condensation with Aldehyde or Ketone Enolate ion attacks a C=O and the alkoxide is protonated. The net result is addition. =>

4 Chapter 224 Condensation with Esters Loss of alkoxide ion results in nucleophilic acyl substitution. =>

5 Chapter 225 Keto-Enol Tautomers Tautomers are isomers which differ in the placement of a hydrogen. One may be converted to the other. In base: =>

6 Chapter 226 Keto-Enol Tautomers (2) Tautomerism is also catalyzed by acid. In acid: =>

7 Chapter 227 Equilibrium Amounts For aldehydes and ketones, the keto form is greatly favored at equilibrium. An enantiomer with an enolizable hydrogen can form a racemic mixture. =>

8 Chapter 228 Acidity of  -Hydrogens pK a for  -H of aldehyde or ketone ~20. Much more acidic than alkane or alkene (pK a > 40) or alkyne (pK a = 25). Less acidic than water (pK a = 15.7) or alcohol (pK a = 16-19). In the presence of hydroxide or alkoxide ions, only a small amount of enolate ion is present at equilibrium. =>

9 Chapter 229 Enolate Reaction => As enolate ion reacts with the electrophile, the equilibrium shifts to produce more.

10 Chapter 2210 Acid-Base Reaction to Form Enolate Very strong base is required for complete reaction. Example: =>

11 Chapter 2211  Halogenation Base-promoted halogenation of ketone. Base is consumed. Other products are water and chloride ion. =>

12 Chapter 2212 Multiple Halogenations The  -halo ketone produced is more reactive than ketone. Enolate ion stabilized by e - -withdrawing halogen. =>

13 Chapter 2213 Haloform Reaction Methyl ketones replace all three H’s with halogen. The trihalo ketone then reacts with hydroxide ion to give carboxylic acid. Iodoform, yellow ppt. =>

14 Chapter 2214 Positive Iodoform for Alcohols If the iodine oxidizes the alcohol to a methyl ketone, the alcohol will give a positive iodoform test. =>

15 Chapter 2215 Acid Catalyzed Halogenation of Ketones Can halogenate only one or two  -H’s. Use acetic acid as solvent and catalyst. =>

16 Chapter 2216 Aldehydes and Halogens Halogens are good oxidizing agents and aldehydes are easily oxidized. =>

17 Chapter 2217 The HVZ Reaction The Hell-Volhard-Zelinsky reaction replaces the  -H of a carboxylic acid with Br. =>

18 Chapter 2218 Alkylation Enolate ion can be a nucleophile. Reacts with unhindered halide or tosylate via S N 2 mechanism. =>

19 Chapter 2219 Stork Reaction Milder alkylation method than using LDA. Ketone + 2  amine  enamine. Enamine is  -alkylated, then hydrolyzed. =>

20 Chapter 2220 Acylation via Enamines Product is a  -diketone. =>

21 Chapter 2221 Aldol Condensation Enolate ion adds to C=O of aldehyde or ketone. Product is a  -hydroxy aldehyde or ketone. Aldol may lose water to form C=C. =>

22 Chapter 2222 Mechanism for Aldol Condensation =>Also catalyzed by acid.

23 Chapter 2223 Dehydration of Aldol Creates a new C=C bond. =>

24 Chapter 2224 Crossed Aldol Condensations Two different carbonyl compounds. Only one should have an alpha H. =>

25 Chapter 2225 Aldol Cyclizations 1,4-diketone forms cyclopentenone. 1,5-diketone forms cyclohexenone. =>

26 Chapter 2226 Planning Aldol Syntheses =>

27 Chapter 2227 Claisen Condensation Two esters combine to form a  -keto ester. =>

28 Chapter 2228 Dieckmann Condensation A 1,6 diester  cyclic (5)  -keto ester. A 1,7 diester  cyclic (6)  -keto ester. =>

29 Chapter 2229 Crossed Claisen Two different esters can be used, but one ester should have no  hydrogens. Useful esters are benzoates, formates, carbonates, and oxalates. Ketones (pK a = 20) may also react with an ester to form a  -diketone. =>

30 Chapter 2230  -Dicarbonyl Compounds More acidic than alcohols. Easily deprotonated by alkoxide ions and alkylated or acylated. At the end of the synthesis, hydrolysis removes one of the carboxyl groups. malonic ester, pK a = 13 acetoacetic ester, pK a =11 =>

31 Chapter 2231 Malonic Ester Synthesis Deprotonate, then alkylate with good S N 2 substrate. (May do twice.) Decarboxylation then produces a mono- or di-substituted acetic acid. =>

32 Chapter 2232 Acetoacetic Acid Synthesis Product is mono- or di-substituted ketone. =>

33 Chapter 2233 Conjugate Additions When C=C is conjugated with C=O, 1,2-addition or 1,4-addition may occur. A 1,4-addition of an enolate ion is called the Michael reaction. =>

34 Chapter 2234 Michael Reagents Michael donors: enolate ions stabilized by two electron-withdrawing groups.   -diketone,  -keto ester, enamine,  -keto nitrile,  -nitro ketone. Michael acceptors: C=C conjugated with carbonyl, cyano, or nitro group.  conjugated aldehyde, ketone, ester, amide, nitrile, or a nitroethylene. =>

35 Chapter 2235 A Michael Reaction Enolates can react with ,  -unsaturated compounds to give a 1,5-diketo product. =>  -keto acid

36 Chapter 2236 Robinson Annulation A Michael reaction to form a  -diketone followed by an intramolecular aldol condensation to form a cyclohexenone. =>

37 Chapter 2237 Mechanism for Robinson Annulation (1) =>

38 Chapter 2238 Mechanism for Robinson Annulation (2) =>

39 Chapter 2239 End of Chapter 22


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