C h a p t e r T w e n t y : Carboxylic Acids & Their Derivatives

Transcription

1 C h a p t e r T w e n t y : Carboxylic Acids & Their Derivatives N C3 N Lysergic acid, the depressant used to make LSD, the famous acid of the 1960s LSD and the Search for God, a San Francisco-based band

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3 CM 323: Summary of Important Concepts YConcepts for Chapter 20: Carboxylic acids and Their Derivatives I. Nomenclature and structure of carboxylic acids A. IUPAC system: Alkanoic acid 1. Drawn as, C 2, C 2. For complex alkanes, name as an aalkanecarboxylic acid B. Common names 1. Most common are a. Formic acid C 2 b. Acetic acid C 3 C 2 c. Benzoic acid II. A. Typically form -bonded dimers Properties B. Are acidic (duh) 1. pk a usually # 5 a. inductive effect b. resonance effect 2. eact with bases to form alkanoates a. micelle formation: basis of soaps, cell membranes C. Spectroscopy 1. NM a. - appears in the 1 NM region δ b. C= appears in the 13 C NM region δ I a. broad - stretch over the region cm -1 b. C= stretch appears in the cm -1 region 177

4 III. eactions A. eduction using LiAl 4 1. LiAl B. Esterifications catalyzed esterification + ' + ' + 2 a. mechanism: ' +.. ' '.. ' ' + + '... + ' + ' + ' +.. ' ' '

5 2. methyl ester formation using diazomethane + C 2 N 2 ether C 3 + N 2 a. mechanism + C N + N + N + N C 3 N N + C. Acyl halide formation + SCl 2 + S 2 + Cl D. Decarboxylation 1. typically observed with β-ketoacids or β-dicarboxylic acids ) (enol) (keto) + C 2 179

6 IV. Derivative classes A. Acid halides CX 1. IUPAC nomenclature alkanoyl halide X Cl ethanoyl chloride (acetyl chloride) Cl benzoyl chloride B. Acid anhydride (C=)(C=) 1. IUPAC nomenclature alkanoic anhydride ethanoic anhydride (acetic anhydride) benzoic anhydride C. Esters C 2 1. IUPAC nomenclature alkyl alkanoate ethyl ethanoate (ethyl acetate) D. Amides CN 2 1. IUPAC nomenclature alkanamide methyl benzoate ethanamide (acetamide) N-methyl benzamide 180

7 2. Common amides formamide N,N-dimethylformamide (DMF) E. Nitriles C/N 1. IUPAC nomenclature alkanenitrile ethanenitrile (acetonitrile) benzenenitrile (benzonitrile) V. eactivities in acyl transfer A. General trend: Acyl halides > Anhydrides > Esters > Amides > Nitriles > Carboxylates B. Interconvertability chart: X SCl 2 ' N 2 C N 181

8 VI. General mechanism of acyl transfer Z + Nu- Z Nu + Z- Nu VII. Types of acyl transfer reactions A. ydrolysis: Nu = 2 1. Substrates... Cl + + Cl Cl- + Cl a. CX, (C=)(C=) b. C 2 i. acid-catalyzed C 3 + C C 3 + C C C

9 ii. in aqueous base (saponification) C + - C C C 3 c. CN 2 i. very similar to esters (be sure you can write reasonable mechanisms) d. C/N i. hydrolyze via amide intermediates B. Alcholysis 1. Substrates a. CX, (C=)(C=) i. mechanistically identical to hydrolysis ii. typical to use 1 equiv of a base (triethylamine, pyridine, or K 2 C 3 ) to neutralize the acid that forms as a co-product b. C 2 (transesterification) i. acid-catalyzed < mechanistically identical to acid-catalyzed hydrolysis C. Ammoniolysis 1. Substrates a. CX, (C=)(C=) i. mechanistically identical to hydrolysis ii. typical to use 2 equiv of ammonia or amine to neutralize the acid that forms as a co-product b. C 2 i. mechanistically identical to base hydrolysis D. Alkylation 1. Substrates a. CX i. form ketones from 2 CuLi CX + 2 CuLi 6 (C=) 183

10 b. C 2 i. form 3E s from MgX or Li < ketones are intermediates 2 MgX + 'C ' 2 C + 2 c. CN 2 i. form ketones with Li < formamides yield aldehydes Li + 'CN 2 6 '(C=) + N 2 E. eduction 1. substrates a. C 2 i. form alcohols using LiAl 4 < aldehydes are intermediates C 2 + LiAl 4 6 C 2 + ii. form aldehydes using DIBAL C 2 + DIBAL 6 C + b. CN 2 i. form amines using LiAl 4 < N-substituted and N,N-disubstituted amides also work well CN 2 + LiAl 4 6 C 2 N 2 c. C/N i. form amines using LiAl 4 CN + LiAl 4 6 C 2 N 2 184

11 1. Provide synthetic routes for reasonable laboratory preparations of the following compound, using a sequence of chemical reactions from your study of organic chemistry. You must begin with the material given, and may use any other organic or inorganic reagents you require. a., prepared from benzoic acid 2. Predict the structure of major organic product produced by each of the following reactions, including stereochemistry where appropriate. If you believe that no reaction will occur with the given conditions, write "N". a. b. Cl 1. LiAl 4, ether

12 c. Br 100 EC 3. Provide a clear, complete mechanism that explains the following chemical reaction: C 3 C 3 C 3 C 2 186

13 4. The reaction conditions given for following reactions may lead to the formation of a major product. Identify that product, including stereochemistry where appropriate. IF there is no reaction, indicate so by writing "N": a C 3 C 2 MgBr b. Cl (C 3 C 2 C 2 ) 2 CuLi ether c. 1. NaB 4, ether 2. 2 d. C 3 1. LiAl 4, TF 2. 2 e. 2 + ) 187

14 5. Provide a clear, complete, correct reaction mechanism for the following transformation: 2 MgBr + 1. ether 2. aq Cl 188

15 6. Using a series of chemical reactions that you have studied inorganic chemistry, propose chemically reasonable syntheses of both of the following compounds. a. 6-methyl-1,2,4-heptanetriol from methyl 3-methylbutanoate and allyl alcohol as the only carbon sources b. ethyl 5-tert-butoxypentanoate from 1,5-pentanediol 189

16 7. Ethyl 5-tert-butoxypentanoate, which you prepared in problem 3 b, above, is found to undergo the following chemical transformation when treated with 1 equiv. Br in acetic acid at room temperature: Br C 3 C 2 T + + Br Propose a clear, complete reaction mechanism that explains how this transformation occurs. 190