Use the roadmap you made for problem 6.54, 7.29, 8.28,

Account for the fact that treatment of tert-butyl methyl ether with a limited amount of concentrated HI gives methanol and tert-butyl iodide rather than methyl iodide and tert-butyl alcohol.

Draw structural formulas for the major products of each reaction. CH3 (Excess) (a) CH3COCH3 1 HBr (b) (Excess) 1 HBr CH3 O

The trimethylsilyl protecting group is easily removed in aqueous solution containing a trace of acid. Propose a mechanism for this reaction. (Note that a TBDMS protecting group is stable under these conditions because of the greater steric crowding around silicon created by the t-butyl group.)

Consider the possibilities for stereoisomerism in the bromohydrin and epoxide formed from trans-2- butene. (a) How many stereoisomers are possible for the bromohydrin? Which of the possible bromohydrin stereoisomers are formed by treating trans-2-butene with bromine in water? (b) How many stereoisomers are possible for the epoxide? Which of the possible stereoisomers is/are formed in this two-step sequence?

Draw the expected products of Sharpless epoxidation of each allylic alcohol using (1)-diethyl tartrate as the chiral catalyst. HO HO OCH3

Write names for these compounds. Where possible, write both IUPAC names and common names. (a) O (b) OCH (c) 3 O OH O O O (d) (h) O O (e) (f) S (g) O

Draw structural formulas for these compounds. (a) 2-(1-Methylethoxy)propane (b) trans-2,3- Diethyloxirane (c) trans -2-Ethoxycyclopentanol (d) Ethenyloxyethene (e) Cyclohexene oxide (f ) 3- Cyclopropyloxy-1-propene (g) (R)-2-Methyloxirane (h) 1,1-Dimethoxycyclohexane

Each compound given in this problem is a common organic solvent. From each pair of compounds, select the solvent with the greater solubility in water. (a) CH2Cl2 and EtOH (b) Et2O and EtOH (d) O (c) Et2Oand Et2O and

Account for the fact that tetrahydrofuran (THF) is very soluble in water, whereas the solubility of diethyl either in water is only 8 g/100 mL water.

Because of the Lewis base properties of ether oxygen atoms, crown ethers are excellent complexing agents for Na1, K1, and NH4 1. What kind of molecule might serve as a complexing agent for Cl2 or Br2?

Write equations to show a combination of reactants to prepare each ether. Which ethers can be prepared in good yield by a Williamson ether synthesis? If there are any that cannot be prepared by the Williamson method, explain why not. (a) O (b) O (c) OMe O (d) (e) (f) OEt O

Draw structural formulas for the products formed when each compound is heated at refl ux in concentrated HI. O O (a) O O O (b) (c) (d)

Following is an equation for the reaction of diisopropyl ether and oxygen to form a hydroperoxide. Diisopropyl ether A hydroperoxide O 1 O2 O O OH Formation of an ether hydroperoxide is a radical chain reaction. (a) Write a pair of chain propagation steps that accounts for the formation of this ether hydroperoxide. Assume that initiation is by a radical, R. (b) Account for the fact that hydroperoxidation of ethers is regioselective; that is, reaction occurs preferentially at a carbon adjacent to the ether oxygen.

Triethanolamine, (HOCH2CH2)3N, is a widely used biological buffer, with maximum buffering capacity at pH 7.8. Propose a synthesis of this compound from ethylene oxide and ammonia.

Ethylene oxide is the starting material for the synthesis Cellosolve, an important industrial solvent. Propose a mechanism for this reaction. H2C CH2 Oxirane (Ethylene oxide) 2-Ethoxyethanol (Cellosolve) H2SO4 1 CH3CH2OH CH3CH2OCH2CH2OH

Ethylene oxide is the starting material for the synthesis of 1,4-dioxane. Propose a mechanism for each step in this synthesis. O OH OH HO HO O O 1,4-Dioxane H1 H1 1 O

Propose a synthesis for 18-crown-6. If a base is used in your synthesis, does it make a difference whether it is lithium hydroxide or potassium hydroxide?

Predict the structural formula of the major product of the reaction of 2,2,3- trimethyloxirane with each set of reagents. (a) MeOH/MeO2Na1 (b) MeOH/H1 (c) Me2NH

The following equation shows the reaction of trans-2,3-diphenyloxirane with hydrogen chloride in benzene to form 2-chloro-1,2-diphenylethanol. trans-2,3-Diphenyloxirane 2-Chloro-1,2- diphenylethanol C6H5 H H C6H5 C C 1 HCl O C6H5CH9CHC6H5 HO Cl (a) How many stereoisomers are possible for 2-chloro-1,2-diphenylethanol? (b) Given that opening of the epoxide ring in this reaction is stereoselective, predict which of the possible stereoisomers of 2-chloro-1,2- diphenylethanol is/are formed in the reaction.

Propose a mechanism to account for this rearrangement. O BF3 Tetramethyloxirane 3,3-Dimethyl-2- butanone O

Acid-catalyzed hydrolysis of the following epoxide gives a trans diol. Only this glycol is formed H2SO4 O H 1 H2O CH3 HO HO H 1 CH3 CH3 HO HO H This glycol is not formed Of the two possible trans diols, only one is formed. How do you account for this stereoselectivity?

Following are two reaction sequences for converting 1,2-diphenylethylene into 2,3-diphenyloxirane. 2,3-Diphenyloxirane 1,2-Diphenylethylene RCO3H PhCH9CHPh PhCH"CHPh O PhCH9CHPh O 2,3- Diphenyloxirane 1. Cl2, H2O 2. CH3O2Na1 Suppose that the starting alkene is trans-1,2- diphenylethylene. (a) What is the confi guration of the oxirane formed in each sequence? (b) Will the oxirane formed in either sequence rotate the plane of polarized light? Explain

The following enantiomer of a chiral epoxide is an intermediate in the synthesis of the insect pheromone frontalin. OH OO O Show how this enantiomer can be prepared from an allylic alcohol, using the Sharpless epoxidation.

Human white cells produce an enzyme called myeloperoxidase. This enzyme catalyzes the reaction between hydrogen peroxide and chloride ion to produce hypochlorous acid, HOCl, which reacts as if it were Cl1OH2. When attacked by white cells, cholesterol gives a chlorohydrin as the major product. Cholesterol Cholesterol chlorohydrin Me Me R white blood cells HO HO Me Cl OH Me R (a) Propose a mechanism for this reaction. Account for both its regioselectivity and stereoselectivity. (b) On standing or (much more rapidly) on treatment with base, the chlorohydrin is converted to an epoxide. Show the structure of the epoxide and a mechanism for its formation. This epoxide is believed to be involved in induction of certain cancers.

Propose a mechanism for the following acid-catalyzed rearrangement. H2SO4, THF O O

Show reagents and experimental conditions to synthesize the following compounds from 1-propanol (any derivative of 1-propanol prepared in one part of this problem may be used for the synthesis of another part of the problem). (a) Propanal (b) Propanoic acid (c) Propene (d) 2-Propanol (e) 2- Bromopropane (f ) 1-Chloropropane (g) 1,2-Dibromopropane (h) Propyne (i) 2-Propanone ( j) 1- Chloro-2-propanol (k) Methyloxirane (l) Dipropyl ether (m) Isopropyl propyl ether (n) 1-Mercapto-2- propanol (o) 1-Amino-2-propanol (p) 1,2-Propanediol

Starting with cis-3-hexene, show how to prepare the following diols. (a) Meso 3,4-hexanediol (b) Racemic 3,4-hexanediol

Show reagents to convert cycloheptene to each of the following compounds. (d) (g) (j) (k) (h) (b) (c) (i) (m) (n) (a) (e) (f) (l) O O H H SEt OH OH OH O NH2 O OMe Br OH O OH OH OH OMe OH CN NH2 OH OH C#CCH3 OH

Show reagents to convert bromocyclopentane to each of the following compounds. O O H H (a) (b) (e) (i) (g) (f) (d) (c) (j) (h) (k) OH OH OH OH Br O OH NEt2 OH OMe O OMe OH C#CH

Given the following retrosynthetic analysis, show how to synthesize the target molecule from styrene and 1-chloro-3-methyl-2-butene. O HO Cl OH O Styrene 1-Chloro-3-methyl-2-butene 1

Starting with acetylene and ethylene oxide as the only sources of carbon atoms, show how to prepare these compounds. (a) 3-Butyn-1-ol (b) 3-Hexyn-1,6-diol (c) 1,6-Hexanedio

Following are the steps in the industrial synthesis of glycerin. Cl2 heat Cl2 NaOH, H2O , H2O CH2"CHCH3 A (C3H5Cl) Ca(OH)2 heat H2O, HCl C (C3H7ClO2) D (C3H6O2) HOCH2CHCH2OH 1,2,3-Propanetriol (glycerol, glycerin) B (C3H6O) Propene OH Provide structures for all intermediate compounds (AD) and describe the type of mechanism by which each is formed.

Gossyplure, the sex pheromone of the pink bollworm, is the acetic Following is a retrosynthetic analysis for (7Z, 11E)-7,11-hexadecadien-1-ol, which then led to a successful synthesis of gossyplure. O9Si9t-Bu OH OH H 1 Br OH Br 1 H OH 1 H Br Br 1 H H O Me Me O9Si9t-Bu Me Me O9Si9t-Bu Me Me 1 2 3 4 5 6 7 8 9 (a) Suggest reagents and experimental conditions for each step in this synthesis. (b) Why is it necessary to protect the 9OH group of 6-bromo-1-hexanol? (c) How might you modify this synthesis to prepare the 7Z,11Z isomer of gossyplure?

Epichlorohydrin (Section 11.10) is a valuable synthetic intermediate because each of its three carbons contains a reactive group. Following is the fi rst step in its synthesis from propene. Propose a mechanism for this step. 5008C 1 Cl Propene 3-Chloropropene (Allyl chloride) Cl2 1 HCl

Each of these drugs contains one or more building blocks derived from either ethylene oxide or epichlorohydrin. Cl N N H Moclobemide (an antidepressant) O O OH (a) NH2 N H Atenolol (an antihypertensive) O O (b) O O Me Me OMe Diphenhydramine (Benadryl, an antihistamine) Spasmolytol (an antispasmodic) N Et Et Br N Br (c) (d) O N N Me N N OH Clozapine (an antischizophrenic) Cetirizine (Zyrtec, an antihistamine) (racemic) O N N H Cl (e) (f) Cl Identify the part of each molecule that can be derived from one or the other of these building blocks and propose structural formulas for the nucleophile(s) that can be used along with either ethylene oxide or epichlorohydrin to synthesize each molecule. We will learn about the actual syntheses of each molecule in later chapters.

Aldehydes and ketones react with one molecule of an alcohol to form compounds called hemiacetals, in which there is one hydroxyl group and one ether-like group. Reaction of a hemiacetal with a second molecule of alcohol gives an acetal and a molecule of water. We study this reaction in Chapter 16. "O 1 H2O The carbonyl group of an aldehyde or ketone A hemiacetal (has an 9OH and an 9OR group to the same carbon) ROH H1 OH OR An acetal (has two 9OR groups to the same carbon) OR OR ROH H1 Draw structural formulas for the hemiacetal and acetal formed from these reagents. The stoichiometry of each reaction is given in the problem. (a) "O 1 2 CH3CH2OH Cyclohexanone Ethanol H1 (b) "O 1 HOCH2CH2OH Cyclohexanone Ethylene glycol H1 O (c) 1 cis-1,2- Cyclohexanediol Acetone H1 OH OH

Use the roadmap you made for problem 6.54, 7.29, 8.28, 9.54, and 10.50, and update it to contain the reactions in the Key Reactions section of this chapter. Because of their highly specifi c nature, do not use reactions 2, 8, and 10 on your roadmap.

Write the products of the following sequences of reactions. Refer to your roadmap to see how the combined reactions allow you to navigate between the different functional groups. (a) 1. Na8 2. OH Br An alcohol (b) Cl 1. 1 Equivalent of KOtBu 2. mCPBA 3. H3O /H2O 1 A haloalkane (c) 1. BH3 2. H2O2/NaOH 3. PBr3 An alkene 4. 1 Equivalent of NaOEt (d) 1. Br2 and light 2. 1 Equivalent of KOtBu 3. MCPBA 4. NH3 An alkane

Using your roadmap as a guide, show how to convert 1-butene into dibutyl ether. You must use 1- butene as the source of all carbon atoms in the dibutyl ether. Show all required reagents and all molecules synthesized along the way. 1-Butene Dibutyl ether ? O

Using your roadmap as a guide, show how to convert cyclohexanol into racemic trans-1,2- cyclohexanediol. Show all required reagents and all molecules synthesized along the way. ? OH OH Cyclohexanol Trans-1,2-cyclohexanediol (racemic) OH OH OH

Using your roadmap as a guide, show how to convert 1-butanol and ethanol into racemic 2-ethoxy-1- butanol. You must use 1-butanol and ethanol as the source of all carbon atoms in the ether product. Show all required reagents and all molecules synthesized along the way. ? O O OH OH OH OH 1- Butanol 1 Ethanol 2-Ethoxy-1-butanol (racemic) 1

During the synthesis of the antiasthmatic drug montelukast (Singulair), a silyl ether protecting group is used to mask the reactivity of an OH group. The silyl group chosen is the tert-butyldimethylsilyl (TBDMS) group. Draw the product of the following transformation, assuming the TBDMS-Cl reagent reacts only once with the starting material. Briefl y explain your answer. HO Imidazole (base) DMF/CH2Cl2 CH3 CH3 CH3 CH3 OH H3C Si N C Cl Cl H3C H3C

The Sharpless epoxidation is used when a single enantiomer product is required. Predict the structure of the predominant product of the following transformation. (2)-Diethyl tartrate Ti(O9iPr)4 tert-Butyl hydroperoxide O Si O OH