Chemistry 251/253

Answer Key

Homework 7

1. In the following reaction, the ethyl propionate was added to a mixture of benzaldehye and sodium ethoxide in ethanol. Draw the structure of the major product.CCOC(=O)C(C)C(O)c1ccccc1

This reaction is a combination of an aldol condensation and a Claisen reaction. The benzaldehyde, which has no a-hydrogens, acts as the electrophilic component, while the ethyl acetate reacts with the NaOEt to produce the nucleophilic component.

2. In the following reaction, the acetaldehyde was added to a mixture of ethyl benzoate and sodium ethoxide in ethanol. Draw the structure of the major product.O=CCC(=O)c1ccccc1

This reaction is a also combination of an aldol condensation and a Claisen reaction. The ethyl benzoate, which has no a-hydrogens, acts as the electrophilic component, while the acetaldehyde reacts with the NaOEt to produce the nucleophilic component.

3. The reaction shown below produced a product with the following ¹H-NMR data: d, ppm 1.26, t, J= 6.8, 3H; 3.21, d, J = 2.6, 2H; 4.18, q, J = 6.8, 2H; 6.55, m, J = 2.6, 5.6, 1H; 6.68, d, J = 5.6, 1H; 7.18-7.58, m, 5H. Draw the structure of the product.CCOC(=O)C1=C(C=CC1)c2ccccc2

This reaction involves an intramolecular nucleophilic addition of an enolate ion to the carbonyl carbon of a ketone. The resulting alcohol undergoes dehydration during the work-up.

4. O=CCC(=O)c1ccccc1 In this reaction the ethyl formate does not have any a-hydrogens, so it can only act as an electrophile. The LDA deprotonates the methyl group of the acetophenone to produce a high concentration of enolate ion, which reacts with the ester in a nucleophilic acyl substitution reaction. Compare this question to question 2.

5.CCC#CC(=O)c1ccccc1 In this reaction the LDA deprotonates the terminal alkyne. The resulting carbanion then acts as a nucelophile in an Sn2 reaction with the ethyl bromide.

6. CC(=O)C(Cc1ccccc1)C(=O)C

7. CC(C)CC(C#N)C(=O)C It is useful to think of the cyano group as a "pseudo-carbonyl group". It stabilizes the conjugate base that is produced by deprotonation of the a-carbon. The pKa of the methylene protons in the starting ketone should be higher than, but close to, 9.

8. No reaction. The NaOEt will deprotonate the b-ketoester completely (K_eq = 10⁶), but the resulting enolate ion will not react with the 1-chloropropene because vinyl halides do not undergo Sn2 reactions. The Sn2 reaction occurs at sp³ hybridized carbon atoms.

9. CCC(=O)c1ccccc1 The first part of this transformation involves saponification of the ester. Acidification of the basic reaction mixture converts the carboxylate salt to the carboxylic acid, which, when heated, undergoes decarboxylation to produce the ketone.

10. CC(C)CCCC=O This is a straightforward alkylation of an aldehyde.

11.CC1CC2C3CCCCC3(C)C=CC2=CC1=O This is a straightforward alkylation of a ketone.

12.CCC(C(=O)CC)C(=O)OC

13. CSC(SC)c1ccccc1 This is an example of the formation of a thioacetal. The reaction is analogous to the nucleophilic addition of alcohols to aldehydes and ketones.

14. CCN(CC)CC1CC2(C)CCCC(C)(C)C2=CC1=O This is an example of a Mannich reaction.

15.CCC=CC(=O)c1ccccc1 In this reaction the methyl protons of the a,b-unsaturated ketone are the most acidic protons. They have a pK of approximately 19. The LDA deprotonates the methyl group and the resulting carbanion attacks the methyl iodide.

16.No reaction.

17.O=C(Cc1ccccc1)Cc2ccccc2 The first part of this sequence involves a Claisen condensation to produce compound A. Saponification of compound A produces the corresponding b-ketocarboxylic acid, which decarboxylates when heated in aqueous acid.

18. Select the compound that you could not prepare fromusing a Mannich reaction:

C The Mannich reaction involves the generation of a nucleophilic carbon atom at a position a to a carbonyl group.

19.The Mannich reaction shown below produces a mixture of isomeric substituted phenols. Select the phrase that best describes the composition of that mixture.

A. the ortho and meta isomers.

B. the ortho and para isomers

C. the meta and para isomers.

D. all three isomers.

You need to draw all the resonance structures that are involved in this reaction to predict the product mixture.

21. How many of these compounds will produce the same product when subjected to saponification followed by vigorous heating in aqueous acid? 2 The third and fourth compounds would produce the same ketone.

Questions 22-27 are related to the structures of 2-bromo-2,3-dichloropropionitrile, , 2,2,3-trichloropropionitrile,, and 2,3-dichloropropionitrile.

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22. The methylene protons in 2-bromo-2,3-dichloropropionitrile are

23. In the ¹H-NMR spectrum of 2-bromo-2,3-dichloropropionitrile the methylene protons would appear as

24. The methylene protons in 2,2,3-trichloropropionitrile are

25. In the ¹H-NMR spectrum of 2,2,3-trichloropropionitrile the methylene protons would appear as

26. In the ¹H-NMR spectrum of 2,3-dichloropropionitrile the methylene protons would appear as

A sawhorse projection of 2,3-dichloropropionitrile, , reveals that H_a and H_b are diastereotopic, which means that they are not identical and that they have different chemical shifts in the ¹H-NMR; H_a splits H_b into a doublet and vice versa. Likewise H_c splits each branch of these two doublets into doublets, so that the methylene protons appear as four doublets. Diagramatically the spin-spin splitting interactions look like this:

27. In 2,3-dichloropropionitrile, when the dihedral angle between the two C-Cl bonds is 180^o, the dihedral angles between H-1 and the two H-2 protons are

The sawhorse projection also shows that the dihedral angle between H_a and H_c is 60^o, while that between H_c and H_b is 180^o. That is why the coupling constants J_BC and J_AC do not have the same values.

28. Which of the following statements best describes the methylene protons in 3-chloro-3-methylpentane, ?

The molecule has a plane of symmetry that passes through the carbon atom of the methyl group attached to C-3, C-3, and the Cl atom attached to C-3. Therefore the two ethyl groups, and therefore the two methylene groups, are identical. However, the protons of the two methylene groups are not identical, they are diastereotopic as the diagram below indicates:

While C-3 of 3-chloro-3-methylpentane is not chiral, replacing H_B of C-2 with a D produces a new structure in which both C-2 and C-3 are chiral. The stereochemistries of the two chiral centers are R and S. respectively. Replacing H_A of C-2 generates a diastereomer of the compound produced by replacing H_B. Its stereochemistry is S,S. Exactly the same situation applies when you consider the two protons attached to C-4.

29. Enter any letters which correspond to reaction conditions that would achieve the following transformation:.ABThe first two steps of sequence D will generate an ester that will react with the ethyl lithium in the third stepto produce the desired product initially. However, that product is more reactive towards ethyl lithium than the ester is, so the actual product that sequence D would produce is .

30. To an organic chemist, the reaction is similar to each of the four reactions shown below. However, one of the four reactions shares a similarity that the others do not. Which one? A In both cases, the acidity of the proton that is abstracted by the base depends upon the ability of the adjacent heteroatom, S or P, to accomodate more than 8 electrons in its valence shell.