Chem 315 Reactions Work Page Beauchamp 1 Acid catalyzed reactions you should be able to write arrow-pushing mechanisms for. Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 2 O O N H SO /HO H2SO4 /H2O 2 4 2 C O H H NH2 (+H O) OH (+H2O) 2 O O O HO H SO /HO 2 4 2 OH add water/acid deprotects alcohols (+H2O) Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 3 OH H OTs OR OR (-H O) 2 OH HO O H2SO4 /H2O H2SO4 /H2O OH O OH (+H2O) (+H2O) Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 4 Some reactions with strong nucleophiles Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 5 Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 6 Examples of acyl substitution reactions, you should be able to write arrow-pushing mechanisms for. O O O O O O O N H OH N Cl O O O O O SH O O Cl S O O O AlCl3 Rriedel-Crafts OH reactions Cl O H O O O H Al H Li R N R H OH HO H N O Cl H O H B H O Na Li O R H very slow reaction Cu O Cl (cuprates) O Al O O O R 1. H (DIBAH) Al O 2. WK H 1. H (DIBAH) Cl H 2. WK O O O O N O R H N H H H O Cl undesired O side rxn. O 2 eqs. OH O 1. Li R R O 2. WK O R (Grignard reagents too) R Cl AlCl3 O H O Rriedel-Crafts 1. Na O reactions R 2. WK R O O O O OH HO OH O H O O O 1. Na O N 2. WK HN OH Tosylates, phosphates, sulfonates, nitrates, all from acid Cls Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 7 Reaction Mechanism Worksheet Guidelines 1. Factors to consider when looking at reactants, reaction intermediates and product(s). a. Are there any resonance effects? b. Are there any inductive effects? c. Are there any steric effects? d. Are there any stereochemical considerations? 2. Where are the pairs of electrons that can be donated? (nucleophilic sites) 3. Which site(s) can accept a pair of electrons? (electrophilic sites) 4. Is the reaction in acid? (A Lewis or Bronsted acid = E+ = strong, the acidity drives the reaction) + a. Usually use a strong acid to supply protons, often the strong acid is the protonated solvent. (ROH2 ), (nonproton Lewis acids can also be species with an empty valency such as BH3, BF3, AlCl3, FeBr3, TiCl4, SbF5, etc. which all complex very well with lone pairs.) b. There are no strong electron pair donors in strong acid (bases or nucleophiles are weak). Often the weak base or leaving group is the neutral solvent. (ROH) 5. Is the reaction in base? (The strong base/nucleophile drives the reaction.) a. Usually use a weak acid to supply protons, usually the neutral solvent, (ROH), or other neutral molecule of similar acidity. b. Usually an anion (often the conjugate base of the solvent) acts as the strong nucleophile, strong base or good leaving group (RO --) 6. Are free radicals or one electron transfers involved? Often a photon or neutral (or reduced) metallic compound is part of the reaction. Oxygen or a peroxide can also serve as a free radical initiator. In mechanism problems of our course include the following. 1. Show all lone pairs of electrons 2. Show all formal charge, when present 3. When resonance is a factor in the stability of an intermediate, draw at least one additional resonance structure, including the “best” resonance structure. 4. Show all curved arrows to show the flow of electrons (full headed arrow = 2 electron movement) 5. Any free radical centers if present (half headed/fish hook arrow = 1 electron movement) Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 8 A few examples and partial examples. (If something seems wrong, it might be. I make mistakes too.) Fill in all necessary mechanistic details (lone pairs, formal charge, curved arrows). Also, fill in blanks. Possible Key TsO H H H O H H O H OTs O O O OH HO OH OH O O OTs functional H ketone group = _____________ hemi-ketal H H common name = ________________ O H H H H O O H H H O H H H O OH O O O O O O O O ketal right common name = ________________ Remove H2O shifts equilibrium to the _________________ left Adding H2O shifts equilibrium to the _________________ Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 9 Related mechanisms 2. Fischer esterification: carboxylic acid + alcohol ester + water (TsOH = cat., remove water) Reverse = H2SO4 / add water 3. aldehydes, ketones + 1o amines imines + water (TsOH = cat., remove water) Reverse = H2SO4 / add water 4. aldehydes, ketones + 2o amines enamines + water (TsOH = cat., remove water) Reverse = H2SO4 / add water o 5. nitrile + water 1 amide (HCl / H2O, via enol-like intermediate) 6. nitrile or amide + water carboxylic acid (H2SO4 / H2O / , via enol-like intermediate) Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 10 7. alkyne + water ketone (H2SO4 / H2O / , via enol) H CH3 + CH2 C O H2SO4 /H2O=H3O C H H R R O (3 steps) R OH (2 steps = tautomers) terminal alkynes water enol tautomer keto tautomer Acyl substitution mechanism in base. Add in all necessary mechanism details (lone pairs, formal charge, curved arrows, resonance structures, etc.). Possible Key Na Na Na O O OR OH R O C R R C O R O O C H H H R O O H ester H O O O O H R O resonance H H alcohol C H C C R O R O R O 2. workup Na carboxylic acid (neutralize carboxylate) Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 11 Predict products and propose mechanisms for the following reactions. Look for common themes. The reactions are not identical, but do share many similarities. Use aqueous/acid conditions and show how each of the products + formed would react. How would any of the forward reactions below, as shown, change if H3O / H2O were the reaction conditions? 1 H H3C O H H3CHO 2 H OH H3C O H H3CHO 3 H H3C O H O H3CHO 4 H H3C O H H3CHO 5 H O H3C O H H3CHO 6 O H H H3C O H O H3CHO 7 H O H3C O H O H3CHO 8 H O H3C O H H CHO 3 Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 12 Supply any necessary, missing mechanistic details (curved arrows, formal charge, lone pairs). 1 H H H H C O H H 3 CH CH2 CH2 2 OCH H3CHO O CH3 H 3 H3CHO H H3C O H 2 H H H H H3C O H CH OH CH2 2 O H H OCH3 H3CHO O CH3 H3CHO H H3C O H 3 H H H H C O H O CH 3 CH2 2 H H OCH O O O CH3 3 H3CHO H H3C O H H H3CHO 4 H H H H H H H3C O H O H H3C H CHO H C O H H 3 H 3 H H C O H H3CHO 3 5 H H H H O O O O H3C O H H H3CHO O O H3C H3C O H H3CHH3CHO 6 H H H H O O O O H C O H H 3 H H H O O O O O O H H3CHO H C H3CH 3 H3CHO H3C O H 7 H H H H O O O O H3C O H O O O O O O H H3CHO H C H3CH 3 H3CHO H3C O H 8 H H OH O O OH H3C O H H H C O H CHO O 3 3 H3C H H3C O H H3CHO Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 13 How do these same compounds compare in base? Three sets of basic conditions have been listed below. Here there are very different observations. Predict which conditions lead to a reaction and where such a reaction occurs, provide a mechanism. Reaction A B Reaction Condition #2C Reaction Condition #1 Condition #3 Na HO Li = LDA N CH3 (MgBr) lithium diisopropylamide 9 10 OH 11 O 12 13 O 14 O H O 15 O O 16 O Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc Chem 315 Reactions Work Page Beauchamp 14 Fill in mechanistic details. H S 2 N C N ? Br H rotate groups to proper "anti" conformation for E2 reaction Br E2 R O H ? SN1 H H H R O E1 Br H H carbocation rearrangement rearrangement E1 SN1 O O O O R H R O H OR O OH O OR O O 1 H 2 Identify the functional groups involved: H 1 = O H OH 2 = H 2.