Ionic Substitution Lab Expt # 10 Chemistry 250-02 Organic Chemistry I Fall, 2014 Day 32 Mon., Nov., 17, 2014 Chapter 11 Alkyl Halides Rδ+-Xδ- Ionic Substitution Lab Expt # 10 Chem Act 13 C, D

R-OH -> R-Cl R-OH -> R-Br Chapter 10

One Step and Two Step Nucleophilic Substitution Chem Activity 13A (13B) and 13C slow (RDS) fast One Step Two Steps

McMurry Problem 11.26 A “Walden” cycle What is the purpose for making B ? What is “OTos” ? Why is [α]D for B positive ? What kind of reaction is B -> C and what is the solvent and the mechanism ? What is the optical purity of C and what are the %’s of the two enantiomers of C ? How could you make C from B with 100 % enantiomeric excess (i.e. optically pure) ? What kind of reaction is D -> E and what is the mechanism ? How can you convert A into CH3-CHCl-CH2 -Phenyl ? into CH3-CHD-CH2 -Phenyl ?

Chem Activity 13

Substrate Steric Effects in SN2 on sp2

How Nucleophiles Affect SN2 Rate increases as nucleophilicity increases Nucleophilicity increases and Periodic Table

How Leaving Groups Affect SN2 Good LG is the Conj Base of a Strong Acid

How Solvents Affect Substitution Polar aprotic accelerate SN2 Polar protic accelerate SN1

Chem Act 14 Table page 220 Favored Mech. Base/Nuc R-X Rate dependent on [??] Solvent Temp SN1 SN2 E1 E2

What statement about the SN2 reaction of methyl bromide with hydroxide is incorrect? The reaction kinetics is first-order in hydroxide. In the transition state the carbon is sp2 hybridized. Absolute configuration is inverted from R to S. The reaction is faster in HMPA than in water. The reaction can be catalyzed by I–.

Consider the reaction of (S)-(–)-1-iodo-2-methylbutane to produce (+)-2-methyl-1-butanol. What is the absolute configuration of the product? R S R and S (racemic mixture) R and S (unequal amounts-scalemic) There is no chiral center in the product

Which of the following is the best nucleophile? (CH3)3N (CH3)2P– (CH3)2O CH3O–

Which of the following reagents is the best nucleophile for an SN2 reaction? methanol methoxide acetate hydroxide water

Which of the following is the product of the SN2 reaction between the hydroxide ion (HO–) and (R)-CH3–CHDI? D = 2H (deuterium) 1. 2. 3. 4. 5.

Select the substrate which would react fastest in the substitution reaction. 1. 2. 3. 4. 5.

Select the reagent and solvent combination which would result in the fastest rate of substitution (R = CH3 in all cases). R-OH, HMPA R-S–, H2O R-O–, H2O R-S–, DMSO R-SH, H2O

Which electrophile will react the fastest by the SN2 mechanism with cyanide (:N≡C:–) in DMF? phenyl iodide (Ph–I) vinyl tosylate (H2C=CH–OTos) ethyl bromide cyclohexyl bromide benzyl tosylate (Ph-CH2-OTos)

Which set of reaction conditions represents the best way to carry out the following transformation? AcOH NaOAc in AcOH NaOAc in H2O NaOAc in DMSO AcOH in HMPA

Which of the following will give the fastest SN1 reaction? 1. 2. 3. 5. 4.

Which set of reaction conditions represents the best way to carry out the following transformation? AcOH NaOAc in AcOH NaOAc in H2O NaOAc in DMSO AcOH in HMPA

Chem Act 13 Exercise 25, Part D, page 200

SN2 It’s not always straight inversion. R. Wester, M. Weidem-ller (U SN2 It’s not always straight inversion ! R. Wester, M. Weidem-ller (U. Freiburg), W. Hase (Texas Tech) Science 2008, 319, 183

SN2 With Retention ! Nucleophilic Substitution Catalyzed by a Supramolecular Cavity Proceeds with Retention of Absolute Stereochemistry Chen Zhao , F. Dean Toste *, Kenneth N. Raymond *, and Robert G. Bergman * Chemical Sciences Division, Lawrence Berkeley National Laboratory, and Department of Chemistry, University of California, Berkeley, California 94720, United States J. Am. Chem. Soc., 2014, 136 (41), pp 14409–14412 DOI: 10.1021/ja508799p Publication Date (Web): September 29, 2014