c. Cyclohexanone Chemistry 262 Homework 2 Part II Winter 2018

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1 Chemistry 262 Homework 2 Part II Winter 2018 The following homework covers Chapter 10 in Loudon & Parise s Organic Chemistry, 6 th ed. and contains 24 questions, valued at point each, as well as 3 bonus questions valued at point each Name: KEY ALCOL AND THIOL ACID BASE CONSIDERATIONS 1. Which of the following has the highest pk a value in aqueous solution? a. Phenol b. Isopropanol c. Cyclohexanone d. Ammonium chloride e. para-toluene sulfonic acid Intended to be an easy opening question cyclohexanone has no heteroatom associated hydrogens. The most acidic H are to the carbonyl, with a typical ketone pk a 19-20, and cyclic ketones a little lower ( 17). Recall ammonia is a weak base, and as such the acid is weakly acidic (pk a = 9.24) ALCOL AND THIOL ACID BASE CONSIDERATIONS 2. Which of the following has the lowest pk a value in aqueous solution? a. Phenol b. Isopropanol c. Cyclohexanone d. Ammonium chloride e. para-toluene sulfonic acid Also intended to be an easy opener Ts (which happens as soon as you expose TsCl to water) is an analog of sulfuric acid (pk a = -3)

2 ALCOL AND THIOL ACID BASE CONSIDERATIONS 3. Which of the following would be substantially (> 10 %) deprotonated by sodium phenoxide (PhONa) a. Phenol b. Ammonium chloride c. para-toluene sulfonic acid d. 2 of the above e. All of the above The problem is how to interpret option (a) since it is the conjugate acid of sodium phenoxide. Treated as unique species (careful reading of the question should lead you to this conclusion since it is implied PhONa is to be added to each of the options) 50 % of the phenol would have been deprotonated (assuming equal amounts). On the other hand, if no means of discriminating which phenol was which was available (e.g. isotopically labeling either the phenol or sodium phenoxide) then the net amount of phenol would not change since every phenoxide that snags a proton become phenol DEHYDRATION OF ALCOLS 4. What is the expected outcome when 3-methyl-1-cyclohexanol is heated in conc. H 3 PO 4? a. 3-methyl-1-cyclohexene b. 1-methyl-1-cyclohexene Credit given for both (a) & (b) c. Cyclohexanone d. Adipic acid (1,6-hexanedioic acid) e. A 1:1 mixture of (a) and (b) conc. H3PO4 No opportunity to rearrange, since hydride shift leads to another 2 o carbocation. H2PO4 - is a stronger base than water. 4-methylcyclohexene also possible. However... H + conc. H3PO4 1,2-Hydride Shift

3 BONUS I: AN ALTERNATIVE PATHWAY TO DIRECT REARRANGEMENT IS REPETITIVE ELIMINATION AND ADDITION. SHOW HOW THIS COULD EXPLAIN THE FORMATION OF 2-METHYL-2-PENTENE FROM 4-METHYL-2-PENTANOL IN AQUEOUS H 2 SO 4 : Essentially shown above DEHYDRATION OF ALCOLS 5. What is the expected outcome when 3-methyl-1-cyclohexanol is heated in conc. HBr? a. 3-methyl-1-cyclohexene b. 1-methyl-1-cyclohexene c. 3-methyl-1-bromocyclohexane d. 1-methyl-1-bromocyclohexane e. All of the above Compared to dihydrogen phosphate, bromide is a much poorer base (H 3 PO 4 pk a = 2.1 HBr pk a = -9) but a decent nucleophile in this polar protic medium (though the reaction tends to go through an S N 1 mechanism. Always bear in mind there are no strong bases available in a strongly acidic environment REACTION OF ALCOLS WITH HYDROGEN HALIDES 6. What is the expected product when 2-methyl-2-propanol reacts with conc. hydrochloric acid? a. Isobutene b. Isobutane c. tert-butyl chloride d. Isobutyl chloride e. sec-butyl chloride This is actually a little trickier than one might expect if you recall S N 1 and E1 arise from a common transition state and are in competition with one another. It is important to bear in mind this is conc. HCl, and even though this translate to 12 M HCl (pure water being 55.5 M), a great deal of the water is occupied in hydrogen bonding the hydronium ions present. Heating the solution would favor elimination

4 BASE COMPATABLE ALCOL-DERIVED LEAVING GROUPS 7. What is the expected product if n-butanol is treated with tosyl chloride in pyridine, followed by tbuok in tbu? a. 1-butene b. 2-butene c. Butyl tert-butyl ether d. (a) and (b) in equal amounts e. (a) and (c) in equal amounts HW 10.39k. True, the possibility of ether formation exists, but tbuok is a rather awkward (you can almost hear the tuba playing) bulky nucleophile BASE COMPATABLE ALCOL-DERIVED LEAVING GROUPS 8. What would be the expected outcome of the following transformation? H SO 2 Cl CO - 2 Product? base C 2 H 5 H 3 CCO 2 H H O 2 C H 3 CCO 2 OSO 2 C 2 H 5 C 2 H 5 C 2 H 5 a. I I II III b. II c. III d. Equal amounts of I & II e. None of the above The formation of the initial mesylate, while an S N 2 process, has no bearing on the chiral carbon bearing the alcohol. The 2 nd reaction is also S N 2, and thus an inversion of configuration ensues. Carboxylates are actually decent nucleophiles, and this can be a thoughtful way of making esters where the alcohol portion is unusual

5 BASE COMPATABLE ALCOL-DERIVED LEAVING GROUPS 9. Which of the following will not convert an alcohol into a good leaving group? a. Tosyl chloride b. Mesyl chloride c. Triflic anhydride d. Dimethyl sulfate e. N/A; all of the above will convert an alcohol into a good leaving group Alkylating an alcohol turns it into an ether, and ethers are poor leaving groups since you would have to lose an alkoxide, the carbon based equivalent of hydroxide (recall alcohols are less acidic than water). It is interesting to contrast this to the use of isobutene in acid as a protecting group say if you wanted to carry out a Grignard and you did not want the alcohol to interfere by forming the t-butyl ether derivative, mild heat and acid would cause the loss of isobutene, returning your initial alcohol, but in no way will the alcohol oxygen be lost. If you methylate as a temporary measure, good luck getting it back off MODERN METHODS FOR CONVERSION OF ALCOLS TO ALKYL HALIDES 10. Which of the following will not convert an alcohol into an alkyl bromide? a. SOBr 2 + pyridine b. PBr 3 + pyridine c. Ph 3 PBr 2 + pyridine d. Conc HBr + heat e. N/A; all of the above will convert an alcohol to an alkyl bromide Yes, SOBr 2 exists (as you can readily rationalize) though it is much less common than SOCl 2 as it decomposes more readily. Remember PBr 3 and 3 PBR s are not the same one goes great with pyridine when halogenating, the other with big trucks and high caliber weaponry

6 MODERN METHODS FOR CONVERSION OF ALCOLS TO ALKYL HALIDES 11. Please show the mechanism by which benzyl alcohol is converted to benzyl chloride by thionyl chloride (SOCl 2 ) in the presence of pyridine (C 5 H 5 N) Cl Pyridinium ion pka = 5 so no chance of deprotonation before initial attack Cl Post initial attack, pyridine plenty strong enough to deprotonate pka est > -2 SO2 lost and pyridinium chloride formed as side products. If system is open & heated, HCl lost and pyridine acts as catalyst ORGANIC REDOX REACTIONS 12. Which of the following compounds is most oxidized? a. CH 4 b. CH 2 Cl 2 c. d. CH 2 O e. CCl 4 Assigning -1 to each higher electronegativity, singly bonded chlorine gives carbon an oxidation number of +4 ORGANIC REDOX REACTIONS 13. Considering only the anisole (phenyl methyl ether), the following is a CH3 a. 2 electron reduction for the reaction overall (+6 left side, +4 right) b. 4 electron reduction c. 2 electron oxidation d. 4 electron oxidation e. None of the above HW 10.48b

7 OXIDATION OF ALCOLS 14. Which of the formal oxidation number on manganese in KMnO 4? a. +4 b. +5 c. +6 d. +7 e. +8 Assign monoatomic ions their charge, assign O -2, and make certain all of the numbers add up to 0 (or the overall charge on an ion) OXIDATION OF ALCOLS 15. What is the final formal oxidation number at C1 after 1-hexanol has been heated with a concentrated alkaline solution of KMnO 4? a. 0 b. +1 c. +2 d. +3 e. +4 Oxidizes to hexanoic acid (2 -2 each, and 1 +1) CHEMICAL AND STEREOCHEMICAL GROUP RELATIONSHIPS 16. How many chemically nonequivalent sets of hydrogens are found in trans-3-hexene? a. 2 b. 3 c. 4 d. 5 e. 6 HW 10.44a (nicely shown in study guide). Note the symmetry.

8 CHEMICAL AND STEREOCHEMICAL GROUP RELATIONSHIPS 17. How many chemically nonequivalent sets of hydrogens are found in 1-bromo-1-chloro-2- methoxyethane? a. 1 b. 2 c. 3 d. 4 e. 5 HW 10.44b (also nicely shown in study guide). Notice the diasterotopic H s on the C bearing the methoxy group CHEMICAL AND STEREOCHEMICAL GROUP RELATIONSHIPS 18. What is the term best describing the methylene hydrogens at C3 in (S)-2-butanol? a. Homotopic b. Enantiotopic c. Diastereotopic d. Prochiral e. (c) and (d) Chiral center already present, and substituting each H in turn leaving existing chiral center alone - necessarily gives rise to diastereomers, since for compounds with more than 1 asymmetric center to exist as enantiomers, all centers must change absolute configuration. The methylene hydrogens are also prochiral, since changing either generates a new chiral center OCTET EXPANSION AND OXIDATION OF THIOLS 19. Which of the following is most oxidized? a. CH 2 SH b. CH 2 SCH 2 c. CH 2 SSCH 2 d. SO 2 Cl e. ( ) 2 SO Pretty easy with the 2 oxygen present. Disulfides are more interesting, and clearly they represent an increase in oxidation state compared to thiols, and are readily generated in mild oxidizing conditions (see following question)

9 OCTET EXPANSION AND OXIDATION OF THIOLS 20. Which of the following will oxidize butanethiol to the corresponding disulfide? a. Conc. HNO 3 b. I 2 in aqueous Na c. KMnO 4 /Na/ d. K 2 Cr 2 O 7 /H 2 SO 4 e. All of the above Gently now, we wouldn t want to over-oxidize to the corresponding sulfonic acid would we? SYNTHESIS OF ALCOLS 21. What principal product would you expect from the following reaction? H 3 O +? I II III a. I b. II c. III d. IV e. V IV IV This reaction was born to rearrange

10 SYNTHESIS OF ALCOLS 22. What principal product(s) would you expect from the following reaction sequence? i) BH 3, THF ii) H 2 O 2,Na? + enantiomer + enantiomer I II III IV a. I b. II c. III d. IV e. III & IV in equal amounts The initial addition of BH 3 is syn, which places it trans to the methyl group RETROSYNTHETIC ANALYSIS 23. Please synthesize butyl methyl ether from n-butanol I refer you to HW 10.39e as a very efficient strategy. Notice there is no chance for elimination in attacking methyl iodide, whereas first converting nbu to nbucl and attacking with NaOMe would diminish the yield slightly RETROSYNTHETIC ANALYSIS 24. Please synthesize di-tert-butyl ether from 2-methyl-2-propanol I refer you to HW 10.40h. Elemental potassium generates tbuok without any elimination since there are no electron pairs for deprotonation. However, when reacted with tbucl, the propensity of tbuok to act as a base instead of a nucleophile becomes apparent. Best to go the mellow route and react tbu in dilute H 2 SO 4

11 BONUS II: PLEASE SYNTHESIZE ETHYL BENZOATE FROM BENZYL ALCOL AND ETHYLENE I refer you to your lab notebooks, and recall all (oxidative) roads lead to benzoic acid. As for the ethanol you are going to couple to it, may I suggest an acid catalyzed alkene hydration? BONUS III: TAKE YOUR PICK OF THE FOLLOWING 2 QUESTIONS ANSWER ONLY ONE QUESTION A. What is the principal drawback to the gasification of coal for energy? C + 2H 2 CH 4 Answer: I would say the major drawbacks are (1) hydrogen is not energetically free, nor is it all that easy to get it to all of these coal deposits. Call me crazy, but finding a large body of water next to your coal deposits, electrolyzing the water to generate H 2 and O 2, then using C as a H 2 trap seems a tad kooky. Besides, when it is all said and done, you will still be generating CO 2 on combustion B. What do you get when you mix tosyl chloride with iceberg lettuce? Answer: A tosyled salad of course

Chemistry 262 Homework 2 Part II Winter 2018

Chemistry 262 Homework 2 Part II Winter 2018 The following homework covers Chapter 10 in Loudon & Parise s Organic Chemistry, 6 th ed. and contains 24 questions, valued at 0.3333 point each, as well as