Organic Chemistry II: Practice Exam #2 Answer Key

1. Propose structures for compounds A-E in the following reaction sequence. The molecular formula for E is provided.

2. Draw structures for the products of any five (5) of the following reactions. If you answer more than five, you will receive credit for the best five.

3. We have seen several examples in which protecting a ketone as a cyclic acetal allows synthesis of hydroxy-ketones such as 1 shown below. If 1 is subsequently heated in the presence of ptoluene sulfonic acid (an acid catalyst, H+), cyclic hemiacetal 2 is produced. Propose a mechanism for the conversion of 1 into 2.

Mechanism

4. Circle the compound in each pair that will have the lower pKa (i.e. will be the stronger acid).

5. Complete one of the two following syntheses. If you do both, you will receive credit for the better one. A. Starting from 1-bromopropane and any other reagents, synthesize 2-methyl-1-pentene.

The key thing to recognize is the presence of an alkene in the final product. This should make you think of a Wittig reaction. The first step in the retrosynthesis shows how the alkene product could come from the corresponding ketone. From there, another step back involves a change of oxidation state to an alcohol. The left half of the molecule could be provided by the starting material while the right half would come from a two carbon aldehyde. The full synthesis is shown below the retrosynthesis and shows how two different carbon-carbon bond-forming reactions are combined to make the final product.

B. Perform the synthesis shown below using any necessary reagents.

This problem looks simple: you could make the organolithium reagent, add propanal, then oxidize with PCC or H2CrO4.. However, as discussed in class, the organolithium reagent would be destroyed by taking a proton from the carboxylic acid group of another molecule. Since we do not know any protecting groups for carboxylic acids, you must first convert it into something that can be protected. For example, reduction to an alcohol allows you to add a THP protecting group. You can then set out to make the new carbon-carbon bond in the product. The retrosynthesis on the next page uses the following logic: the ketone in the final product likely came from an alcohol, since we know several ways to make a new C-C bond with an alcohol as the final product, but no methods (yet!) to make a new C-C bond with a ketone as the product. At the same time, the carboxylic acid can be retrod to a primary alcohol. Thinking forwards from this point, you would use H2CrO4.to oxidize the alcohols to the required ketone and carboxylic acid.
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The next two steps show where the new C-C bond came from: an organolithium reagent (or Grignard) at the carbon where the bromine is attached in the starting material reacts with an aldehyde to yield the secondary alcohol. Introducing the THP protecting group at the appropriate time allows the organolithium reagent to be made and reacted with the propanal. The last retro step (and first forward step) shows conversion of the carboxylic acid into something that can be protected, an alcohol.

6. Solve one of the two following problems. If you do both, I will count the one on which you do better. A. Compound 1 is converted into compound 2 by reaction with chromic acid (H2CrO4). Based on the spectral data provided below, propose structures for 1 and 2. 1 (C5H8O2): IR (1710 cm-1), 1H-NMR 9.8 (s, 1H); 2.4 (t, 2H); 2.3 (t, 2H); 2.0 (s, 3H) 2 (C5H8O3)

There are two unsaturations in both compounds. NMR information for 1 gives an aldehyde (CHO), two CH2 groups and one CH3. This leaves CO from the formula, meaning that a ketone is likely present (also indicated by the IR). This is also consistent with the chemical shifts of the methyl and methylene groups. The only way to combine the five fragments to give a structure with the proper splitting is shown above. Chemical information (oxidation with chromic acid) indicates that the aldehyde is converted into a carboxylic acid. This matches the formula. B. Compound 3 has 1H-NMR spectral data given below. Based on this information, propose a structure for 3 and also write the structure of the product (4) that would form upon reaction of 3 with CH3MgBr followed by HCl/H2O. 3 (C9H18O2): IR (1710 cm-1); 1H-NMR 9H) 4.6 (s, 2H); 3.5 (s, 3H); 2.2 (t, 2H); 1.8 (t, 2H); 1.4 (s,

There is one unsaturation in 3 and the IR data indicates that this is a carbonyl. There is no aldehyde or carboxylic acid proton in the NMR spectrum, so this is likely a ketone. However, there are two oxygens in the molecule, so the second oxygen is either present as an alcohol or an ether. There is no signal in the NMR that integrates for one proton, so it cannot be an alcohol, so the second oxygen probably has two carbons bonded to it. The NMR data indicate the presence of a tbutyl group (s, 9H), two adjacent CH2 groups (two t, 2H), and isolated CH2 (s, 2H) and CH3 (s, 3H) groups. The chemical shifts for these last two groups are downfield, so it is likely that these are adjacent to the oxygen. The structure shown for 3 matches the NMR data.