WILLIAM H. BROWN THOMAS POON www.wiley.com/college/brown CHAPTER SEVEN Haloalkanes Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-1 Structure • Haloalkane (alkyl halide): A compound containing a halogen atom covalently bonded to an sp3 hybridized carbon. – given the symbol RX Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-2 Nomenclature - IUPAC – Locate the parent alkane. – Number the parent chain to give the substituent encountered first the lower number. – Show halogen substituents by the prefixes fluoro, chloro-, bromo-, and iodo- and list them in alphabetical order with other substituents. – Locate each halogen on the parent chain. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-3 Nomenclature • Several polyhaloalkanes are common solvents and are generally referred to by their common or trivial names. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-4 Freons & Their Alternatives • The Freons are chlorofluorocarbons (CFCs) – Among the most widely used are/were – Much lower ozone-depleting alternatives are the hydrofluorocarbons (HFCs) and the hydrochlorofluorocarbons (HCFCs), including Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-5 Substitution & Elimination • In this chapter we, concentrate on two types of reactions: Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-6 Nucleophilic Substitution • In the following general reaction, substitution takes place on an sp3 hybridized (tetrahedral) carbon. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-7 Nucleophilic Substitution Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-8 Mechanism • Chemists propose two limiting mechanisms for nucleophilic substitutions. – A fundamental difference between them is the __________ of bond breaking and bond forming steps. • At one extreme, the two processes take place simultaneously;______________________. –S= –N= –2= – rate = k[haloalkane][nucleophile] Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-9 SN 2 – Both reactants are involved in the transition state of the rate-determining step. – The nucleophile attacks the reactive center from _____________________ the leaving group. The key step is reaction of a nucleophile and an electrophile to form a new covalent bond. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-10 SN 2 • Figure 7.1 An energy diagram for an SN2 reaction. – There is one transition state and no reactive intermediate. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-11 SN 1 • In the other limiting mechanism, bond breaking between carbon and the leaving group is ______________________before bond forming with the nucleophile begins. • This mechanism is designated SN1 where – S = substitution – N = nucleophilic –1= – rate = k[haloalkane] Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-12 SN 1 • SN1 is illustrated by the solvolysis* of tertbutyl bromide. – Step 1: Break a bond to form a stable ion or molecule. Ionization of the C-X bond gives a carbocation. *A reaction in which a solvent molecule (like water or alcohol) is also one of the reactants Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-13 SN 1 – Step 2: Reaction of a nucleophile and an electrophile to form a new covalent bond. – Step 3: Take a proton away. Proton transfer to methanol completes the reaction. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-14 SN 1 Figure 7.2 An energy diagram for an SN1 reaction. There are two transition states and one intermediate. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-15 SN1 and Carbocation Rearrangements When an SN1 reaction occurs from a 2° haloalkane, a 2° carbocation is formed, which is prone to rearrange to a more stable 3° carbocation (Section 5.4). Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-16 SN 1 • For an SN1 reaction at a stereocenter, the product is a racemic mixture. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-17 Evidence for SN Reactions • Let us examine some of the experimental evidence on which these two mechanisms are based and, as we do, consider the following questions. – What affect does the structure of the _______________ have on the rate of reaction? – What effect does the structure of the _______________ have on the rate of reaction? – What effect does the structure of the ________ _________have on the rate of reaction? – What is the role of the _____________? Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-18 Nucleophilicity • Nucleophilicity: a kinetic property measured by the rate at which a Nu: attacks a reference compound under a standard set of experimental conditions. – For example, the rate at which a set of nucleophiles displaces bromide ion from bromoethane in ethanol at 25 °C. • Table 7.2 shows common nucleophiles and their relative nucleophilicities Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-19 Relative Nucleophilicity Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-20 Summary • Consider the rate of each reaction type: – Sn2: rate = k[haloalkane][nucleophile] – Sn1: rate = k[haloalkane] • Because the rate of the nucleophile is only considered in Sn2 mechanisms, the following conclusion can be drawn: Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-21 Summary • Strong Nucleophiles favor _____ mechanism • Weak nucleophiles disfavors Sn2 mechanism and allows the Sn1 mechanism to compete successfully • Blue book problems 9.12 – 9.17 (p. 217) Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-22 Structure of the Haloalkane • SN1 reactions – Governed by __________________, namely the relative stabilities of carbocation intermediates. – Relative rates: • SN2 reactions – Governed by __________________, namely the relative ease of approach of the nucleophile to the site of reaction. – Relative rates: Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-23 Structure of the Haloalkane • Steric factors – Compare access to the reaction center in bromoethane and 2-bromo-2-methylpropane (tert-butyl chloride). Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-24 Structure of the Haloalkane • Figure 7.3 Effect of electronic and steric factors in competition between SN1 and SN2 reactions of haloalkanes. Blue Book 9.2 – 9.5 and 9.7 – 9.10 (p. 214) Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-25 The Leaving Group – The best leaving groups in this series are the halogens I–, Br–, and Cl–. (Generally, Good LG are conjugate bases of strong acids!) – OH–, RO–, and NH2– are such poor leaving groups that they are rarely if ever displaced in nucleophilic substitution reactions. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-26 The Leaving Group • Hydroxide ion, OH–, is a poor leaving. However, the –OH group of an alcohol can act as a leaving group, H2O, if the –OH group is first protonated by an acid to form —OH2+, a better leaving group. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-27 Blue Book page 218 & 219 Blue Book 9.19 – 9.26 Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-28 The Solvent • Protic solvent: a solvent that contains an –OH group and is a hydrogen bond donor. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-29 The Solvent • Aprotic solvent: A solvent that does not contain an –OH group and is not a hydrogen bond donor. – Aprotic solvents favor SN2 reactions. Although the solvents at the top of the table are polar, formation of carbocations in them is more difficult than in protic solvents. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-30 Summary of SN1 and SN2 Reactions of Haloalkanes Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-31 Nucleophilic Substitution – Example: Predict the product of each reaction, its mechanism, and the stereochemistry of the product. For more practice, blue book page 224: 9.30 – 9.35 Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-32 b-Elimination • β-Elimination: Removal of atoms or groups of atoms from adjacent carbons to form a ________________________________. – We study a type of b-elimination called ____________________ (the elimination of HX). Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-33 b-Elimination • Zaitsev’s rule: The major product of a β-elimination is the more stable (the more highly substituted) alkene. When cis-trans isomerism is possible, the trans isomer is favored. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-34 b-Elimination • There are two limiting mechanisms for β-elimination reactions. • E1 mechanism: at one extreme, breaking of the C-X bond is complete before reaction with base breaks the C-H bond. – Only R-X is involved in the rate-determining step. • E2 mechanism: at the other extreme, breaking of the C-X and C-H bonds is concerted. – Both R-X and base are involved in the ratedetermining step. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-35 E1 Mechanism – Step 1: Break a bond go give a stable molecule or ion. Rate-determining ionization of C-X gives a carbocation intermediate and halide ion. – Step 2: Take a proton away. Proton transfer from the carbocation to a base (in this case, the solvent) gives the alkene. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-36 E2 Mechanism • A one-step mechanism; all bond-breaking and bond-forming steps are concerted. Simultaneously (1) take a proton away and (2) break a bond to form a stable ion or molecule. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-37 Elimination Reactions Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-38 Substitution versus Elimination • Because many nucleophiles are also strong bases (OH– and RO–), SN and E reactions often compete. – The ratio of SN/E products depends on the _____________________ of the two reactions. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-39 SN1 versus E1 • Reactions of 2° and 3° haloalkanes in polar protic solvents give mixtures of substitution and elimination products. Product ratios are difficult to predict. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-40 SN2 versus E2 • It is considerably easier to predict the ratio of SN2 to E2 products. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-41 Summary of SN versus E for Haloalkanes – Examples: Predict the major product and the mechanism for each reaction. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 7-42