Chemistry 22 Homework set 9

Chem 22 Homework set 9 1. Suggest a method for converting benzoyl chloride to each of the following. (a) benzaldehyde-d (PhCD=O) (b) N-ethylbenzamide (c) benzyl 2-propenoate (d) isopropyl benzoate (e) benzophenone, Ph2C=O (f) PhC(CH3)=NCH3 (g) PhC(CH3)2OH 2. Write the mechanism of each of the following reactions. (Note that the amino acid produced by hydrolysis of the lactam (a) should be protonated — sorry, but I'm not going to redraw it) H N (a) O H+ H2O H2N CO2H (b) O O (b) H+, H2O (c) HO–, H2O and draw the product (3-hydroxypropanoic acid in the first case; its conj base in the second) 3. Following the fate of an 18O label can provide insight into the mechanism of reactions of carboxylic acid derivatives. For example, consider the course of the acid-catalyzed hydrolysis of an ester labelled with 18O in the carbonyl group. (a) Write the hydrolysis mechanism. (b) Based on your mechanism, where would you expect the label to end up? That is, which oxygen(s) of the products would be 18O? (c) When the hydrolysis is allowed to go about half way to completion, and the "unreacted" ester is reisolated, some of the 18O is found to have been completely "washed out", i.e. replaced with the common isotope 16O. Explain how that happens. (Hint: Focus on the fate the neutral geminal-dihydroxy compound, RC(OH)2OR'.) (d) When a similarly labelled amide is partially hydrolyzed, the reisolated amide is found to have virtually all of its 18O label intact. Why doesn't the label wash out like it does in the ester hydrolysis? (Again, focus on the fate of the geminal-dihydroxy intermediate, RC(OH)2NR'2.) Chem 22 Spring 2010 Name _________________________________________ HW set 9 25 points; due Wed, April 7 at the beginning of class. 1. Hydrolysis of a benzoate ester is shown below. When R = ethyl, the reaction proceeds by the mechanism that you learned in class. One piece of evidence supporting this mechanism is that when ethyl benzoate is hydrolyzed in 18O-labelled water (i.e. 18OH2 instead of the usual 16OH2), all of the 18O ends up in the carboxylic acid, not the alcohol. (a) Write the mechanism, showing the fate of the label. A common way to show an isotopically labeled O is by coloring in the "O" with a pencil. Does your mechanism show the label ending up in the right place? O Ph O R H2O H+ Ph CO2H + ROH (b) An alternative might have been an SN2 attack by labelled water on the ethyl group of the protonated ester. Where would the label have ended up in this case? (c) When the ester having R = tert-butyl is hydrolyzed in 18O-labelled water, the 18O label ends up entirely in the alcohol, not in the acid. Write a mechanism that explains this result. (Don't even think about proposing an SN2 attack on a 3° C!) (d) Why does the tert-butyl ester react via a different mechanistic pathway? 2. Suggest methods for preparing the compounds below from benzoyl chloride (PhCOCl). (a) HO D Ph (b) OCH3 Ph (c) Ph N