CHM 251 Organic Chemistry I s1

CHM 251 Organic Chemistry I Homework #3 Due: Friday, December 10, 2004 by 5:00 pm

1. Iodide anion is a good nucleophile and sodium iodide is quite soluble in acetone. On the other hand, sodium chloride and sodium bromide have low solubilities in acetone. As a result, the reaction of alkyl bromides and alkyl chlorides with NaI/acetone can serve as a simple test as indicated below.

The reactivity order of the following alkyl bromides with NaI/acetone is as follows:

Explain the observed reactivity order. What type of reaction is likely occurring here (SN1, SN2, E1, E2)?

2. Predict the reactivity order for the following alkyl chlorides with NaI/acetone based upon what you learned in questions #1. Explain your ordering.

3. The optical rotation of a solution of (+)-2-bromobutane (opt. rot. = +45°) in diethyl ether does not change with time. However, when tetrabutylammonium bromide (draw this molecule and calculate formal charges) is dissolved in solution, the optical rotation decreases slowly with time to ZERO. The NMR spectrum of the solution does NOT change. Clearly explain what is happening (in terms of a reaction mechanism) and include structural representations. Why does the rotation decrease to zero? Why doesn’t it become negative? 4. Explain the following observation:

5. When 4-chloro-2-methyl-2-pentene reacts with acetic acid (solvent), two substitution products are formed with one product predominating versus the other. When small amounts of the acetate anion are added to the reaction mixture, no change in rate is observed.

(a) The minor isomeric product can actually exist in two different stereochemical forms as a result of the course of this reaction. What are the structures corresponding to each of these products and what is the stereochemical relationship between the two? Are they likely to be formed in equal quantities?

relationship

stereoisomer #1 stereoisomer #2

(b) Provide a complete reaction mechanism that explains how the two different stereoisomers of the minor product are formed. (c) In part (b), you should have generated a key intermediate structure. This is not the most stable form of this intermediate. SHOW (using the curved arrow formalism) how this intermediate alters itself to achieve a more stable configuration of groups. If resonance is involved, be sure to draw all of the possible resonance contributors. How does this affect the percentage of regioisomers formed (major vs. minor)?

starting intermediate ending intermediate

(d) Overall, what is the reaction that is occurring here (SN1, SN2, E1, E2) and why does the addition of small amounts of the acetate not affect the rate of reaction?

6. Complete the table below in which you will rank the carbocations shown in DECREASING order of stability. Be sure to indicate the type(s) of special effects that are contributing to the relative stability of each ion. For those ions that exhibit a resonance stabilization effect --- show ALL possible resonance structures.

Order of stability Stabilizing Effects (Reason for ranking)

(most stable) =

(least stable) =

7. Given the following incomplete reaction:

H3C O Na (S)-3-iodo-3-methylhexane H2O

(a) Draw a skeletal structure for the reactant in the reaction showing the correct stereochemistry.

(b) Draw a CIRCLE around the nucleophile in the reaction. (c) Draw a SQUARE around the best leaving group in the reaction. (d) Place a CHECK MARK next to the any electrophilic carbons. (e) Is the leaving group attached to a primary, secondary, or tertiary carbon?

(f) Do you have a good leaving group or poor leaving group?

(g) Is your nucleophile a strong base or weak base?

(h) Do you have a good nucleophile or a poor nucleophile?

(i) What type of solvent is used in this reaction – PAD or PPD (See SAM pg. 10)? Why do we want to use this type of solvent in this case?

(j) Given your answers to parts (e-i), do you think this reaction is more likely SN1 or SN2?

(k) Provide a mechanism showing all relevant transition states/intermediates for the reaction chosen.

(l) Provide skeletal structure(s) of the expected major product(s). (m) Draw a fully labeled reaction energy diagram that is consistent with your chosen type of reaction

Be sure to answer the following questions AFTER drawing your energy diagram. (a) Which species does the first transition state resemble more closely? (b) Which species does the second transition state resemble more closely? (c) Which step describes the rate-determining step? (d) Use the bond dissociation energies listed pages 36 and 355 of your book to estimate the H for the reaction. Use this value to calculate the Keq for this reaction. Is the reaction exothermic or endothermic as written? Explain.

- 8. The azide ion (N3 ) is known to react by an SN2 mechanism thousands of times more rapidly with 2-bromopentane than with its constitutional isomer neopentyl bromide (1-bromo-2,2- dimethylpropane), despite the fact that the leaving group is at a secondary carbon in the first compound and at a primary carbon in the second. Explain these facts by drawing/interpreting their structures.

2-bromopentane neopentyl bromide 9. To reach the conclusion that the reaction of the azide ion with 2-bromopentane in the

previous problem (#8) did indeed occur as an SN2 reaction, the chemists studying the reaction did several additional experiments. Predict what the scientists would have observed in each

experiment if the reaction really took place via an SN2 pathway.

(a) they used optically active (R)-2-bromopentane

(b) they doubled the concentration of the alkyl bromide

(c) they doubled the concentration of the azide ion

10. Consider the reaction shown below.

H N + NaCN +

(a) Name the amine reactant (on the left).

(b) Circle the most acidic hydrogen in the amine reactant (on the left). (c) The other compound is sodium cyanide. What type of compound is sodium cyanide? What is the role of CN? What is the role of Na?

Type of compound =

Role of CN =

Role of Na =

(d) Realizing that the amine and sodium cyanide will react with one another in an acid-base reaction, use the curved-arrow formalism to show the flow of electrons as the reaction proceeds from reactants to products (forward direction). You may have to redraw NaCN. (e) Which species is acting as your Bronsted-Lowry acid? Which species is acting as your Bronsted-Lowry base?

B.L. acid = B.L. base = (f) Which species is your nucleophile (Lewis base) and which is your electrophile (Lewis acid)?

Nucleophile (Lewis base) = Electrophile (Lewis acid) =

(g) Which species will utilize its HOMO and which will utilize its LUMO in the reaction?

Utilizes HOMO = Utilizes LUMO =

(h) Draw the structures for the expected products of this reaction based upon the mechanism you derived in part (d) – place in the boxes provided (above).

(i) Report the appropriate pKa values for both acids in your equilibrium. (j) Designate each of the species in your reaction as a strong acid (SA), strong base (SB), weak acid (WA), or weak base (WB) – label directly on the reaction above. (k) Show the conjugate acid-base pairs – show directly on the reaction above. (l) For the amine product (after hydrogen removal), draw all important resonance structures to show how resonance contributes significantly to stabilizing this anion.

(m) Calculate the net pKa (from the individual pKa’s)

(n) Convert your net pKa to an overall Ka.

(o) Use the Ka from part (n) to find G°rxn at room temperature (26 °C).

(p) Is this a product or reactant favored equilibrium? Explain.