Total 100 ALLOWED: Periodic System of the Elements (printed, w/o handwriting on it). Molecular models (you can bring pre-made models). Simple, non-programmable calculator (not really needed). NOT ALLOWED: Books. Notes. Electronic devices of any kind (other than a simple calculator).
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Question 1. Enols and Aldol Reactions. (20 points) (a) Butanal (H3C−CH2−CH2−CHO) is an enolizable aldehyde. Draw the two important resonance forms of the anion formed by deprotonation of butanal. Show all lone pairs and formal charges; use the correct resonance arrow. Use curved arrows to show the electron flow that converts one resonance forms into the other. (6 points)
(b) Draw the structure of the mosquito repellent 2-ethylhexane-1,3-diol (a.k.a. “6-12”). This pesticide can be prepared in two steps beginning with butanal. The first reaction is a base-catalyzed aldol reaction of butanal. Provide structural formula of butanal aldol. The second reaction is a __hydrogenation___ and requires a catalyst such as __Ni__. (6 points)
“6-12”, 2-ethylhexane-1,3-diol
Butanal Aldol
(c) Cinnamaldehyde (H5C6−CH=CH−CHO) and dibenzalacetone (H5C6−CH=CH−CO−CH=CH −C6H5) can be prepared in two-step sequences consisting of an aldol reaction and thermal condensation. These syntheses involve a _mixed or crossed_ aldol reaction between the non-enolizable aldehyde __benzaldehyde__ with either the enolizable aldehyde __acetaldehyde__ or the enolizable ketone ____acetone____. (4 points) (d) Draw the structure of the product of the aldol condensation reaction of cinnamaldehyde with acetone in the presence of NaOH. (4 points)
Partial credit (2 pts) for the aldol product (i.e., product before condensation): (Ph−CH=CH−CH(OH)−CH2)2CO
Expected Product
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Question 2. Carboxylic Acids. (20 points) (a) Carboxylic acids form strongly bonded dimeric aggregates (homodimers). The electrostatic potential surface plot is shown of the homodimer of formic acid (HCOOH)2. In very dilute solution, formic acid will be monomeric and form hydrogen bonds with water molecules. One structure (HCOOH)(H2O) is particularly interesting because the water molecule acts both as HB-donor and HB acceptor to the same carboxylic acid and the electrostatic potential surface plot of this aggregate also is shown. Draw the complete structural formula of both aggregates in the space above the plot. Your structure drawing should be aligned as much as possible with the orientation of the molecules in the ESP plots. Indicate H-bonds as dashed lines. (8 points)
(b) Syntheses of carboxylic acids. Provide substrate, reagent or product as requested. (12 points)
Product formed by oxidation of propylbenzene, C6H5−C3H7 with hot KMnO4:
Product formed by oxidation of o-xylene, with hot KMnO4:
Reagent used for the oxidation of glyoxal, OHC−CHO to oxalic acid:
CrO3, or K2Cr2O7
in sulfuric acid
Reagent that reacts with the Grignard reagent formed from tert-butylbromide (H3C)3CBr to form
(H3C)3C−COOH after workup with dilute acid:
O=C=O
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Question 3. Carboxylic Acid Esters. (20 points) (a) Ethyl acetate H3C−CO−O−CH2−CH3 can be made by Fischer esterification of the carboxylic acid ______________ (formic acid, acetic acid, benzoic acid) and the alcohol __________ (methanol, ethanol, phenol). Consider the mechanism of the formation of ethyl acetate by Fischer esterification, that is, the ester formation catalyzed by a strong mineral acid. Draw the structural formulas of the species indicated (show all lone pairs and formal charges). You may abbreviate the methyl group as “H3C−” or as “Me−” and the ethyl group as “H5C2−” or as “Et−”. (14 points)
1: Protonated carboxylic acid, i.e., the actual substrate for alcohol addition
2: Product formed by addition of alcohol to the protonated carboxylic acid
3: Neutral gem tri-functional intermediate
4: Protonated gem tri-functional intermediate that will lead to water elimination
(b) γ-Hydroxybutyric acid (GHB), a.k.a. “Lollipops”, “Liquid Ecstasy”, “Liquid X”, “Liquid G”, and “Fantasy”, is one of the three most common date rape drugs. GHB is easily synthesized by reaction of γ-butyrolactone (GBL) with NaOH. GBL itself is a prodrug because it is converted to GHB in vivo. Draw the structural formulas of the species indicate (show lone pairs, formal charges). (6 points)
Structure of GHB
Geminal tri-functional intermediate in the ester hydrolysis of GBL with NaOH
Structure of GBL
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Question 4. Carboxylic Acid Halides and Anhydrides. (20 points) (a) Consider the preparation of acetyl chloride from acetic acid using _________ (PCl3, PCl4, PCl5, (HO)3PCl2, (HO)2PCl3, OPCl3). Draw structural formulas of the substrate, of the reagent, of the organic product (the acetyl chloride), and also of the inorganic products. (8 points)
(b) Succinic acid is the trivial name of butanedioic acid (note “butane”). Succinic anhydride is the intramolecular anhydride of succinic acid. Draw the structure of succinic anhydride in the box to the right. (2 points) (c) Malic acid is the trivial name of Z-butenedioic acid (note “butene”). Draw the structure of malic anhydride in the box to the right. Maleic anhydride ____ (is, is not) an intramolecular anhydride. (2 points) (d) Fumaric acid is the trivial name of E-butene-dioic acid (note “butene”). Draw the structure of fumaric anhydride in the box to the right. Fumaric anhydride ____ (is, is not) an intramolecular anhydride. (2 points) (e) Suggest a synthesis of benzoic acetic anhydride. Your synthesis should result only in the mixed anhydride without formations of acetic anhydride or benzoic anhydride. Draw structural formulas of the substrates and of the organic product (the mixed anhydride). (6 points)
Full credit for the alternative rxn: Ph-CO-Cl + acetate (i.e., exchange Me and Ph).
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Question 5. Carboxylic Acid Amides. (20 points) (a) Consider the electronic structure of N-methylacetamide, H3C−CO−NH−CH3. This amide is a very simple model of a peptide bond. Provide complete Lewis-Kekule structures of the major resonance forms of the molecule and indicate their relative contributions (i.e., “minor” or “major”). Specify the preferred N-hybridization for each of the resonance forms. Discuss whether the amino group is pyramidal or whether it is planar. (8 points)
(b) Draw the structure of the product of hydrolysis of alanine dipeptide, HOOC−CH(CH3)−NH−CO−CH(CH3)−NH2 in the presence of NaOH. [Hint: Account for salt formation.] (4 points) 2 molecules of (c) Consider the formation of N,N-dimethylacetamide, H3C−CO−N(CH3)2 by reaction of acetic anhydride with dimethylamine. Two molecules of the amine are required for every molecule of acetic anhydride used. Show reaction equations for the reaction A of the first amine with the anhydride and for the reaction B of the second amine with the _acetic acid_ formed in the preceding reaction. (8 points)
