Would you expect the reaction of propyl bromide with sodium cyanide (NaCN), that is

Give IUPAC names for each of the following.

Classify each of the following organic halides as primary, secondary, tertiary, alkenyl, or aryl.

Write the following as net ionic equations and designate the nucleophile, substrate, and practice Problem 6.3 leaving group in each reaction: (a) CH3I + CH3CH2ONa 9: CH3OCH2CH3 + NaI (b) NaI + CH3CH2Br 9: CH3CH2I + NaBr (c) 2 CH3OH + (CH3)3CCl 9: (CH3)3COCH3 + CH3OH2 + Cl(d) NaCN Br CN 9: NaBr (e) Br 2 NH3 NH2 9: NH4Br

Draw a hypothetical free-energy diagram for the SN2 reaction of iodide anion with 1-chlorobutane. Label the diagram as in Fig. 6.4, and assume it is exergonic but without specific values for DG and DG8.

Using chair conformational structures (Section 4.11), show the nucleophilic substitution reaction that would take place when trans-1-bromo-4-tert-butylcyclohexane reacts with iodide ion. (Show the most stable conformation of the reactant and the product.)

SN2 reactions that involve breaking a bond to a chirality center can be used to relate configurations of molecules because the stereochemistry of the reaction is known. (a) Illustrate how this is true by assigning R,S configurations to the 2-chlorobutane enantiomers based on the following data. [The configuration of (-)-2-butanol is given in Section 5.8C.] (+)-2-Chlorobutane 9: HOSN2 (-)-2-Butanol [A]d 25 = +36.00 Enantiomerically pure [A]d 25 = -13.52 Enantiomerically pure (b) When optically pure (+)-2-chlorobutane is allowed to react with potassium iodide in acetone in an SN2 reaction, the 2-iodobutane that is produced has a minus rotation. What is the configuration of (-)-2-iodobutane? Of (+)-2-iodobutane?

Rank the following carbocations in order of increasing stability:

Keeping in mind that carbocations have a trigonal planar structure, (a) write a structure for the carbocation intermediate and (b) write structures for the alcohol (or alcohols) that you would expect from reaction of iodocyclohexane in water: H2O SN1 (CH3)3C I CH3

What product(s) would you expect from the methanolysis of the iodocyclohexane practice Problem 6.9 derivative given as the reactant in Practice Problem 6.8?

The relative rates of ethanolysis of four primary alkyl halides are as follows: CH3CH2Br, 1.0; CH3CH2CH2Br, 0.28; (CH3)2CHCH2Br, 0.030; (CH3)3CCH2Br, 0.00000042. (a) Is each of these reactions likely to be SN1 or SN2? (b) Provide an explanation for the relative reactivities that are observed.

For example, the hydroxide ion (HO-) is a stronger base than a cyanide ion (Niw C-); at equilibrium it has the greater affinity for a proton (the pKa of H2O is 16, while the pKa of HCN is 10). Nevertheless, cyanide ion is a stronger nucleophile; it reacts more rapidly with a carbon bearing a leaving group than does hydroxide ion. practice Problem 6.12 Rank the following in terms of decreasing nucleophilicity: CH3CO2 - CH3OH CH3O- CH3CO2H Niw C

Rank the following in terms of decreasing nucleophilicity in a protic solvent. CH3CO2 - CH3O- CH3S- CH3SH CH3OH

Classify the following solvents as being protic or aprotic: formic acid, HCO2H; acetone, CH3COCH3; acetonitrile, CH3Ciw N; formamide, HCONH2; sulfur dioxide, SO2; ammonia, NH3; trimethylamine, N(CH3)3; ethylene glycol, HOCH2CH2OH.

Would you expect the reaction of propyl bromide with sodium cyanide (NaCN), that is, CH3CH2CH2Br + NaCN 9: CH3CH2CH2CN + NaBr to occur faster in DMF or in ethanol? Explain your answer.

Which would you expect to be the stronger nucleophile in a polar aprotic solvent? Practice Problem 6.16 (a) CH3CO2 - or CH3O- (b) H2O or H2S (c) (CH3)3P or (CH3)3N

When tert-butyl bromide undergoes solvolysis in a mixture of methanol and water, the Practice Problem 6.17 rate of solvolysis (measured by the rate at which bromide ions form in the mixture) increases when the percentage of water in the mixture is increased. (a) Explain this occurrence. (b) Provide an explanation for the observation that the rate of the SN2 reaction of ethyl chloride with potassium iodide in methanol and water decreases when the percentage of water in the mixture is increased.

List the following compounds in order of decreasing reactivity toward CH3O- in an SN2 reaction carried out in CH3OH: CH3F, CH3Cl, CH3Br, CH3I, CH3OSO2CF3, 14CH3OH.

Starting with (S)-2-bromobutane, outline syntheses of each of the following compounds: (R)-CH3CHCH2CH3 OCH2CH3 (a) (R)-CH3CHCH2CH3 SH (c) O (R)-CH3CHCH2CH3 OCCH3 (b) (R)-CH3CHCH2CH3 SCH3

Which SN2 reaction of each pair would you expect to take place more rapidly in a protic solvent? (a) (1) Cl O Cl EtO or (2) Cl O EtOH HCl (b) (1) 9: Cl Cl or (2) 9: (C6H5) (c) (1) 3N or (2) (C6H5)3P 9: Br (d) (1) (1.0 M) MeO (1.0 M) 9: Br (1.0 M) MeO (2.0 M) 9: Br or (2) EtO EtS Br 9: Cl Cl O S Br Br Br OMe Br OMe N(C6H5)3 P(C6H5)3

Which SN1 reaction of each pair would you expect to take place more rapidly? Explain your answer. (a) (1) H2O 9: HCl (2) H2O 9: HBr or (e) (1) H2O 9: HCl (2) H2O 9: HCl or (b) (1) H2O 9: HCl (2) MeOH 9: HCl or (c) (1) EtO (1.0 M) (1.0 M) 9: Cl (2) or EtOH EtO (2.0 M) (1.0 M) 9: Cl EtOH (d) (1) EtO (1.0 M) (1.0 M) 9: Cl (2) or EtOH EtO (1.0 M) (2.0 M) 9: Cl EtOH Cl OH Br OH Cl OH Cl OH Cl OMe Cl OEt Cl OEt Cl OEt Cl OEt

Show how you might use a nucleophilic substitution reaction of 1-bromopropane to synthesize each of the following compounds. (You may use any other compounds that are necessary.) (a) OH (b) 1-Iodopropane (c) O (d) CH3CH2CH2iSiCH3 (e) O O (f) N3 (g) N(CH3)3 Br (h) N (i) SH

With methyl, ethyl, or cyclopentyl halides as your organic starting materials and using any needed solvents or inorganic reagents, outline syntheses of each of the following. More than one step may be necessary and you need not repeat steps carried out in earlier parts of this problem. (a) CH3I (b) I (c) CH3OH (d) OH (e) CH3SH (f) SH (g) CH3CN (h) CN (i) CH3OCH3 (j) OMe

Listed below are several hypothetical nucleophilic substitution reactions. None is synthetically useful because the product indicated is not formed at an appreciable rate. In each case provide an explanation for the failure of the reaction to take place as indicated. (d) Br (a) HO CH3 (e) NH3 CH3OCH3 CH3NH2 CH3OH CH3NH3 (f) NH3 CH3OH2 H2O (b) HO H (c) HO Br CN OH OH OH

Your task is to prepare styrene by one of the following reactions. Which reaction would you choose to give the better yield of styrene? Explain your answer. (1) KOH EtOH, Br or (2) KOH EtOH, Br Styrene Styrene

Your task is to prepare isopropyl methyl ether by one of the following reactions. Which reaction would give the better yield? Explain your answer. (1) CH3ONa I Isopropyl methyl ether OCH3 or CH3 (2) I ONa OCH3 Isopropyl methyl ether

Starting with an appropriate alkyl halide and using any other needed reagents, outline syntheses of each of the following. When alternative possibilities exist for a synthesis, you should be careful to choose the one that gives the better yield. (a) Butyl sec-butyl ether (b) S (c) Methyl neopentyl ether (d) Methyl phenyl ether (e) CN (f) O O (g) (S)-2-Pentanol (h) (R)-2-Iodo-4-methylpentane (i) (j) cis-4-Isopropylcyclohexanol (k) H CN (l) trans-1-Iodo-4-methylcyclohexane

Which product (or products) would you expect to obtain from each of the following reactions? In each part give the mechanism (SN1, SN2, E1, or E2) by which each product is formed and predict the relative amount of each product (i.e., would the product be the only product, the major product, a minor product, etc.?).(a) EtO EtOH, 50 C (b) t -BuOK t -BuOH, 50 C t -BuOK t -BuOH, 50 C (c) MeO MeOH, 50 C (d) Br Br Br Br acetone, 50 C (e) t-Bu I Cl MeOH, 25 C (f) t-Bu Cl (g) 3-Chloropentane 9999: MeOMeOH, 50 C (h) 3-Chloropentane 99999: CH3CO2 - CH3CO2H, 508C (i) (R)-2-bromobutane 99: HO25C (j) (S)-3-Bromo-3-methylhexane 99: 258C MeOH (k) (S)-2-Bromooctane 9999:

Although ethyl bromide and isobutyl bromide are both primary halides, ethyl bromide undergoes SN2 reactions more than 10 times faster than isobutyl bromide does. When each compound is treated with a strong base/nucleophile (EtO-), isobutyl bromide gives a greater yield of elimination products than substitution products, whereas with ethyl bromide this behavior is reversed. What factor accounts for these results?

Consider the reaction of I - with CH3CH2Cl. (a) Would you expect the reaction to be SN1 or SN2? The rate constant for the reaction at 608C is 5 * 10-5 L mol-1 s-1 . (b) What is the reaction rate if [I -] = 0.1 mol L-1 and [CH3CH2Cl] = 0.1 mol L-1 ? (c) If [I -] = 0.1 mol L-1 and [CH3CH2Cl] = 0.2 mol L-1 ? (d) If [I -] = 0.2 mol L-1 and [CH3CH2Cl] = 0.1 mol L-1 ? (e) If [I -] = 0.2 mol L-1 and [CH3CH2Cl] = 0.2 mol L-1 ?

Which reagent in each pair listed here would be the more reactive nucleophile in a polar aprotic solvent? (a) EtO EtOH, 50 C (b) t -BuOK t -BuOH, 50 C t -BuOK t -BuOH, 50 C (c) MeO MeOH, 50 C (d) Br Br Br Br acetone, 50 C (e) t-Bu I Cl MeOH, 25 C (f) t-Bu Cl (g) 3-Chloropentane 9999: MeOMeOH, 50 C (h) 3-Chloropentane 99999: CH3CO2 - CH3CO2H, 508C (i) (R)-2-bromobutane 99: HO25C (j) (S)-3-Bromo-3-methylhexane 99: 258C MeOH (k) (S)-2-Bromooctane 9999: I - MeOH, 508C (a) CH3NH or CH3NH2 (b) CH3O- or CH3CO2 - (-OAc) (c) CH3SH or CH3OH (d) (C6H5)3N or (C6H5)3P (e) H2O or H3O+ (f) NH3 or +NH4 (g) H2S or HS(h) CH3CO2 - (-OAc) or HO

Write mechanisms that account for the products of the following reactions: (a) HO HO H2O O Br (b) H2N HO H2O N

Draw a three-dimensional representation for the transition state structure in the SN2 reaction of Niw C:- (cyanide anion) with bromoethane, showing all nonbonding electron pairs and full or partial charges.

Many SN2 reactions of alkyl chlorides and alkyl bromides are catalyzed by the addition of sodium or potassium iodide. For example, the hydrolysis of methyl bromide takes place much faster in the presence of sodium iodide. Explain.

Many SN2 reactions of alkyl chlorides and alkyl bromides are catalyzed by the addition of sodium or potassium iodide. For example, the hydrolysis of methyl bromide takes place much faster in the presence of sodium iodide. Explain.

Consider the general problem of converting a tertiary alkyl halide to an alkene, for example, the conversion of tert-butyl chloride to 2-methylpropene. What experimental conditions would you choose to ensure that elimination is favored over substitution? (b) Consider the opposite problem, that of carrying out a substitution reaction on a tertiary alkyl halide. Use as your example the conversion of tert-butyl chloride to tert-butyl ethyl ether. What experimental conditions would you employ to ensure the highest possible yield of the ether?

1-Bromobicyclo[2.2.1]heptane is extremely unreactive in either SN2 or SN1 reactions. Provide explanations for this behavior.

Give structures for the products of each of the following reactions: (a) NaI (1 mol) C5H8FI NaBr H Br F H acetone (b) NaI (1 mol) acetone Cl Cl (1 mol) C6H12ClI NaCl (c) Br NaS Br SNa (1 mol) C4H8S2 2 NaBr (d) NaH (H2) Et2O Et2O, heat Cl C4H8ClONa C4H8O NaCl OH (e) NaNH2 (NH3) liq. NH3 C3H3Na 9: C4H6 NaI CH3I

When tert-butyl bromide undergoes SN1 hydrolysis, adding a common ion (e.g., NaBr) to the aqueous solution has no effect on the rate. On the other hand, when (C6H5)2CHBr undergoes SN1 hydrolysis, adding NaBr retards the reaction. Given that the (C6H5)2CH+ cation is known to be much more stable than the (CH3)3C+ cation (and we shall see why in Section 15.12A), provide an explanation for the different behavior of the two compounds.

When the alkyl bromides (listed here) were subjected to hydrolysis in a mixture of ethanol and water (80% EtOH/20% H2O) at 55 8C, the rates of the reaction showed the following order: (CH3)3CBr 7 CH3Br 7 CH3CH2Br 7 (CH3)2CHBr Provide an explanation for this order of reactivity.

The reaction of 18 alkyl halides with nitrite salts produces both RNO2 and RONO. Account for this behavior.

What would be the effect of increasing solvent polarity on the rate of each of the following nucleophilic substitution reactions? (a) Nu: + RiL 9: RiNu + + :L- (b) RiL + 9: R+ + :L

Competition experiments are those in which two reactants at the same concentration (or one reactant with two reactive sites) compete for a reagent. Predict the major product resulting from each of the following competition experiments: (a) DMF I Cl Cl (b) acetone H2O

In contrast to SN2 reactions, SN1 reactions show relatively little nucleophile selectivity. That is, when more than one nucleophile is present in the reaction medium, SN1 reactions show only a slight tendency to discriminate between weak nucleophiles and strong nucleophiles, whereas SN2 reactions show a marked tendency to discriminate. (a) Provide an explanation for this behavior. (b) Show how your answer accounts for the following: NaCN (0.01 M) EtOH Cl CN Major product NaCN (0.01 M) EtOH Cl OEt Major product

The reaction of chloroethane with water in the gas phase to produce ethanol and hydrogen chloride has H8 = +26.6 kJ mol-1 and S 8 = +4.81 J K-1 mol-1 at 25 8C. (a) Which of these terms, if either, favors the reaction going to completion? (b) Calculate G8 for the reaction. What can you now say about whether the reaction will proceed to completion?c) Calculate the equilibrium constant for the reaction. (d) In aqueous solution the equilibrium constant is very much larger than the one you just calculated. How can you account for this fact?

When (S)-2-bromopropanoic acid [(S)-CH3CHBrCO2H] reacts with concentrated sodium hydroxide, the product formed (after acidification) is (R)-2-hydroxypropanoic acid [(R)-CH3CHOHCO2H, commonly known as (R)-lactic acid]. This is, of course, the normal stereochemical result for an SN2 reaction. However, when the same reaction is carried out with a low concentration of hydroxide ion in the presence of Ag2O (where Ag+ acts as a Lewis acid), it takes place with overall retention of configuration to produce (S)-2-hydroxypropanoic acid. The mechanism of this reaction involves a phenomenon called neighboring-group participation. Write a detailed mechanism for this reaction that accounts for the net retention of configuration when Ag+ and a low concentration of hydroxide are used

(R)-(3-Chloro-2-methylpropyl) methyl ether (A) on reaction with azide ion (N3 - ) in aqueous ethanol gives (S)-(3-azido-2-methylpropyl) methyl ether (B). Compound A has the structure ClCH2CH(CH3)CH2OCH3. (a) Draw wedgedashed wedgeline formulas of both A and B. (b) Is there a change of configuration during this reaction?

Predict the structure of the product of this reaction: NaOH in aqueous EtOH HS C6H10S Cl The product has no infrared absorption in the 16201680-cm-1 region

cis-4-Bromocyclohexanol 99: t@BuOt@BuOH racemic C6H10O (compound C) Compound C has infrared absorption in the 16201680-cm-1 and in the 35903650-cm-1 regions. Draw and label the (R) and (S) enantiomers of product C.

1-Bromo[2.2.1]bicycloheptane is unreactive toward both SN2 and SN1 reactions. Open the computer molecular model at the books website titled 1-Bromo[2.2.1]bicycloheptane and examine the structure. What barriers are there to substitution of 1-bromo[2.2.1]bicycloheptane by both SN2 and SN1 reaction mechanisms?

Open the computer molecular model titled 1-Bromo[2.2.1]bicycloheptane LUMO at the books website for the lowest unoccupied molecular orbital (LUMO) of this compound. Where is the lobe of the LUMO with which the HOMO of a nucleophile would interact in an SN2 reaction?

In the previous problem and the associated molecular model at the books website, you considered the role of HOMOs and LUMOs in an SN2 reaction. (a) What is the LUMO in an SN1 reaction and in what reactant and species is it found? (b) Open the molecular model at the books website titled Isopropyl Methyl Ether Carbocation LUMO. Identify the lobe of the LUMO in this carbocation model with which a nucleophile would interact. (c) Open the model titled Isopropyl Methyl Ether Carbocation HOMO. Why is there a large orbital lobe between the oxygen and the carbon of the carbocation?

Consider the solvolysis reaction of (1S,2R)-1-bromo-1,2-dimethylcyclohexane in 80% H2O/20% CH3CH2OH at room temperature. (a) Write the structure of all chemically reasonable products from this reaction and predict which would be the major one. (b) Write a detailed mechanism for formation of the major product. (c) Write the structure of all transition states involved in formation of the major product.

Consider the following sequence of reactions, taken from the early steps in a synthesis of v-fluorooleic acid, a toxic natural compound from an African shrub. (v-Fluorooleic acid, also called ratsbane, has been used to kill rats and also as an arrow poison in tribal warfare. Two more steps beyond those below are required to complete its synthesis.) (i) 1-Bromo-8-fluorooctane + sodium acetylide (the sodium salt of ethyne) 9: compound A (C10H17F) (ii) Compound A + NaNH2 9: compound B (C10H16FNa) (iii) Compound B + Ii(CH2)7iCl 9: compound C (C17H30ClF) (iv) Compound C + NaCN 9: compound D (C18H30NF) (a) Elucidate the structures of compounds A, B, C, and D above. (b) Write the mechanism for each of the reactions above. (c) Write the structure of the transition state for each reaction.