Organic Chemistry Lecture 9th Edition Chapter 6 PDF

Organic Chemistry, 9th Edition L. G. Wade, Jr. Chapter 6 Lecture Alkyl Halides;...

Organic Chemistry, 9th Edition L. G. Wade, Jr. Chapter 6 Lecture Alkyl Halides; Nucleophilic Substitution Chad Snyder, PhD Grace College © 2017 Pearson Education, Inc. © 2014 Pearson Education, Inc.  Classes of Alkyl Halides Alkyl halides: Halogen H H is directly bonded to an H C C Br sp3 carbon. H H Vinyl halides: Halogen alkyl halide H H is bonded to an sp2 C C carbon of alkene. H Cl Aryl halides: Halogen is I vinyl halide bonded to an sp2 carbon on a benzene ring. aryl halide © 2017 Pearson Education, Inc.  Polarity and Reactivity Halogens are more electronegative than C. Carbon–halogen bond is polar, so carbon has partial positive charge. Carbon can be attacked by a nucleophile. Halogen can leave with the electron pair. © 2017 Pearson Education, Inc.  IUPAC Nomenclature Name as a haloalkane. Choose the longest carbon chain, even if the halogen is not bonded to any of those carbons. Use lowest possible numbers for position. 1 2 1 2 3 4 1 2 3 4 5 6 7 2-chlorobutane 4-(2-fluoroethyl)heptane © 2017 Pearson Education, Inc.  Examples 1 2 3 4 5 6 7 8 9 6-bromo-2-methylnonane cis-1-bromo-3-fluorocyclohexane © 2017 Pearson Education, Inc.  Systematic Common Names The alkyl groups is a substituent on halide. It is useful only for small alkyl groups. isobutyl bromide sec-butyl bromide tert-butyl bromide © 2017 Pearson Education, Inc.  Common Names of Halides CH2X2 is called methylene halide. CHX3 is a haloform. CX4 is carbon tetrahalide. Common halogenated solvents: – CH2Cl2 is methylene chloride. – CHCl3 is chloroform. – CCl4 is carbon tetrachloride. © 2017 Pearson Education, Inc.  Alkyl Halides Classification Methyl halides: Halide is attached to a methyl group. Primary alkyl halide: Carbon to which halogen is bonded is attached to only one other carbon. Secondary alkyl halide: Carbon to which halogen is bonded is attached to two other carbons. Tertiary alkyl halide: Carbon to which halogen is bonded is attached to three other carbons. © 2017 Pearson Education, Inc.  Primary, Secondary, and Tertiary Alkyl Halides © 2017 Pearson Education, Inc.  Types of Dihalides Geminal dihalide: Two halogen atoms are bonded to the same carbon. Vicinal dihalide: Two halogen atoms are bonded to adjacent carbons. © 2017 Pearson Education, Inc.  Uses of Alkyl Halides Industrial and household cleaners Anesthetics – CHCl3 was used originally as a general anesthetic but it is toxic and carcinogenic. – CF3CHClBr is a mixed halide and is sold as Halothane. Freons are used as refrigerants and foaming agents. – Freons can harm the ozone layer, so they have been replaced by low-boiling hydrocarbons or carbon dioxide. Pesticides such as DDT are extremely toxic to insects but not as toxic to mammals. – Haloalkanes can not be destroyed by bacteria, so they accumulate in the soil to a level that can be toxic to mammals, especially humans. © 2017 Pearson Education, Inc.  Dipole Moments Electronegativities of the halides: F > Cl > Br > I Bond lengths increase as the size of the halogen increases: C—F < C—Cl < C—Br < C— I Bond dipoles C—Cl > C—F > C—Br > C— I 1.56 D 1.51 D 1.48 D 1.29 D Molecular dipoles depend on the geometry of the molecule. © 2017 Pearson Education, Inc.  Dipole Moments and Molecular Geometry Notice how the four, symmetrically oriented polar bonds of the carbon tetrahalides cancel to give a molecular dipole moment of zero. © 2017 Pearson Education, Inc.  Boiling Points Greater intermolecular forces, higher b. p. – Dipole–dipole attractions are not significantly different for different halides. – London forces are greater for larger atoms. Greater mass = higher b. p. Spherical shape decreases b. p. (CH3)3CBr CH3(CH2)3Br 73 °C 102 °C © 2017 Pearson Education, Inc.  Densities Alkyl fluorides and alkyl chlorides (those with just one chlorine atom) are less dense than water (1.00 g/mL). Alkyl chlorides with two or more chlorine atoms are denser than water. All alkyl bromides and alkyl iodides are denser than water. © 2017 Pearson Education, Inc.  Preparation of Alkyl Halides Free radical halogenation (Chapter 4) – Chlorination produces a mixture of products. This reaction is not a good lab synthesis, except in alkanes where all hydrogens are equivalent. – Bromination is highly selective. Free radical allylic halogenation – Halogen is placed on a carbon directly attached to the double bond (allylic). © 2017 Pearson Education, Inc.  Halogenation of Alkanes Chlorination is not selective. Bromination is highly selective: 3° carbons > 2° carbons > 1° carbons © 2017 Pearson Education, Inc.  Allylic Bromination Allylic radicals are resonance stabilized. Bromination occurs with good yield at the allylic position (sp3 C next to C C). © 2017 Pearson Education, Inc.  Reaction Mechanism The mechanism involves an allylic radical stabilized by resonance. Both allylic radicals can react with bromine. © 2017 Pearson Education, Inc.  N-Bromosuccinimide N-Bromosuccinimide (NBS) is an allylic brominating agent. It keeps the concentration of Br2 low. © 2017 Pearson Education, Inc.  Example of Allylic Halogenation with NBS © 2017 Pearson Education, Inc.  Reactions of Alkyl Halides © 2017 Pearson Education, Inc.  The SN2 Reaction The halogen atom on the alkyl halide is replaced with the nucleophile (HO–). Since the halogen is more electronegative than carbon, the C—I bond breaks heterolytically and the iodide ion leaves. © 2017 Pearson Education, Inc.  SN2 Mechanism Bimolecular nucleophilic substitution (SN2) Concerted reaction: New bond forming and old bond breaking at same time Reaction is second order overall. Rate = kr[alkyl halide][nucleophile] © 2017 Pearson Education, Inc.  SN2 Energy Diagram The SN2 reaction is a one-step reaction. Transition state is highest in energy. © 2017 Pearson Education, Inc.  Uses for SN2 Reactions © 2017 Pearson Education, Inc.  SN2: Nucleophilic Strength Stronger nucleophiles react faster. Strong bases are strong nucleophiles, but not all strong nucleophiles are basic. © 2017 Pearson Education, Inc.  Basicity Versus Nucleophilicity Basicity is defined by the equilibrium constant for abstracting a proton. Nucleophilicity is defined by the rate of attack on the electrophilic carbon atom © 2017 Pearson Education, Inc.  HINT Steric hindrance (bulkiness) hinders nucleophilicity more than it hinders basicity. © 2013 Pearson Education, Inc. Chapter 6 29  Trends in Nucleophilicity A negatively charged nucleophile is stronger than its neutral counterpart: Nucleophilicity decreases from left to right: It increases down periodic table as size and polarizability increase: © 2017 Pearson Education, Inc.  Polarizability Effect Bigger atoms have a soft shell that can start to overlap the carbon atom from a farther distance. © 2017 Pearson Education, Inc.  Solvent Effects: Protic Solvents Polar protic solvents have acidic hydrogens (O—H or N—H) that can solvate the nucleophile, reducing their nucleophilicity. Nucleophilicity in protic solvents increases as the size of the atom increases. © 2017 Pearson Education, Inc.  Solvent Effects: Aprotic Solvents Polar aprotic solvents do not have acidic protons and, therefore, cannot hydrogen bond. Some aprotic solvents are acetonitrile: DMF, acetone, and DMSO. SN2 reactions proceed faster in aprotic solvents. © 2017 Pearson Education, Inc.  Crown Ethers Crown ethers solvate the cation, so the nucleophilic strength of the anion increases. Fluoride becomes a good nucleophile. © 2017 Pearson Education, Inc.  Leaving Group Ability The best leaving groups are Electron-withdrawing, to polarize the carbon atom. Stable (not a strong base) once they have left. Polarizable, to stabilize the transition state. © 2017 Pearson Education, Inc.  HINT Do not write SN2 reactions that show hydroxide ions, alkoxide ions, or other strong bases serving as leaving groups. © 2013 Pearson Education, Inc. Chapter 6 36  Structure of Substrate on SN2 Reactions Relative rates for SN2: CH3X > 1° > 2° >> 3° Tertiary halides do not react via the SN2 mechanism due to steric hindrance. © 2017 Pearson Education, Inc.  Effect of Substituents on the Rates of SN2 Reactions © 2017 Pearson Education, Inc.  Steric Effects of the Substrate on SN2 Reactions Nucleophile approaches from the back side. It must overlap the back lobe of the C—X sp3 orbital. © 2017 Pearson Education, Inc.  Stereochemistry of SN2 SN2 reactions will result in an inversion of configuration also called a Walden inversion. © 2017 Pearson Education, Inc.  Back-Side Attack in the SN2 Reaction © 2017 Pearson Education, Inc.  HINT (R) and (S) are just names. Don’t rely on names to determine the stereochemistry of a reaction. © 2013 Pearson Education, Inc. Chapter 6 42  The SN1 Reaction The SN1 reaction is a unimolecular nucleophilic substitution. It has a carbocation intermediate. Rate = kr[alkyl halide] Racemization occurs. © 2017 Pearson Education, Inc.  SN1 Mechanism Step 1: Formation of the carbocation Step 2: Attack of the nucleophile If the nucleophile is an uncharged molecule like water or an alcohol, the positively charged product must lose a proton to give the final uncharged product. © 2017 Pearson Education, Inc.  SN1 Mechanism: Step 1 Formation of carbocation (rate-determining step) © 2017 Pearson Education, Inc.  SN1 Mechanism: Step 2 The nucleophile attacks the carbocation, forming the product. © 2017 Pearson Education, Inc.  SN1 Mechanism: Step 3 If the nucleophile is neutral, a third step (deprotonation) will be needed. © 2017 Pearson Education, Inc.  SN1 Energy Diagram Forming the carbocation is an endothermic step. Step 2 is fast with a low activation energy. © 2017 Pearson Education, Inc.  Rates of SN1 Reactions Order of reactivity follows stability of carbocations (opposite to SN2). – 3° > 2° > 1° >> CH3X – A more stable carbocation requires less energy to form. A better leaving group will increase the rate of the reaction. © 2017 Pearson Education, Inc.  Substituent Effects SN1 reactivity: 3° > 2° > 1° > CH3X © 2017 Pearson Education, Inc.  SN2 vs SN1: Nucleophilic Strength Stronger nucleophiles react faster SN2. Weak nucleophiles favor SN1. © 2017 Pearson Education, Inc.  Solvation Effect Polar protic solvent is best because it can solvate both ions strongly through hydrogen bonding. © 2017 Pearson Education, Inc.  Structure of the Carbocation Carbocations are sp2 hybridized and trigonal planar. The lobes of the empty p orbital are on both sides of the trigonal plane. Nucleophilic attack can occur from either side, producing mixtures of retention and inversion of configuration if the carbon is chiral. © 2017 Pearson Education, Inc.  Carbocation Stability Carbocations are stabilized by inductive effect and by hyperconjugation. © 2017 Pearson Education, Inc.  Stereochemistry of SN1 The SN1 reaction produces mixtures of enantiomers. There is usually more inversion than retention of configuration. © 2017 Pearson Education, Inc.  Rearrangements Carbocations can rearrange to form a more stable carbocation. Move the smallest group on the adjacent carbon: – Hydride shift: H– on adjacent carbon moves. – Methyl shift: CH3– on adjacent carbon moves. © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc.  Hydride and Methyl Shifts Since a primary carbocation cannot form, the methyl group on the adjacent carbon will move (along with both bonding electrons) to the primary carbon, displacing the bromide and forming a tertiary carbocation. The smallest groups on the adjacent carbon will move: If there is a hydrogen, it will give a hydride shift. © 2017 Pearson Education, Inc.  SN1 or SN2 Mechanism? © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc.