Organic Chemistry Second Edition David Klein Chapter 21

21. 14 Synthetic Strategies Copyright © 2015 John Wiley & Sons, Inc. All rights

21. 3 Structure and Properties of Carboxylic Acids • In water, the equilibrium generally

21. 3 Structure and Properties of Carboxylic Acids • How does the p. Ka

Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry

21. 4 Preparation of Carboxylic Acids • In earlier chapters, we have already learned

21. 4 Preparation of Carboxylic Acids • Let’s examine two more ways to make

21. 4 Preparation of Carboxylic Acids • This gives us a second method to

21. 5 Reactions of Carboxylic Acids • Li. Al. H 4 is a strong

21. 5 Reactions of Carboxylic Acids • The more mild borane reagent can also

21. 6 Introduction to Carboxylic Acid Derivatives • When Z is a heteroatom, the

21. 7 Reactivity of Carboxylic Acid Derivatives • Carboxylic acid derivatives have electrophilic sites

21. 7 Reactivity of Carboxylic Acid Derivatives • Reactivity can be affected by –

21. 7 Reactivity of Carboxylic Acid Derivatives • Let’s examine the acid chloride –

21. 7 Reactivity of Carboxylic Acid Derivatives • Amides are the least reactive acid

21. 7 Reactivity of Carboxylic Acid Derivatives • Aldehydes and ketones are also electrophilic,

21. 7 Reactivity of Carboxylic Acid Derivatives • Nucleophilic acyl substitution is a two-step

21. 7 Reactivity of Carboxylic Acid Derivatives • Let’s analyze a specific example •

21. 7 Reactivity of Carboxylic Acid Derivatives • Do NOT draw the acyl substitution

21. 7 Reactivity of Carboxylic Acid Derivatives • Neutral nucleophiles are generally less reactive,

21. 7 Reactivity of Carboxylic Acid Derivatives • Depending on reaction conditions, up to

21. 7 Reactivity of Carboxylic Acid Derivatives • Give necessary reaction conditions and a

21. 8 Preparation and Reaction of Acid Chlorides • Acid chlorides have great synthetic

21. 8 Preparation and Reaction of Acid Chlorides Copyright © 2015 John Wiley &

21. 8 Preparation and Reaction of Acid Chlorides • The mechanism is more favored

21. 8 Preparation and Reaction of Acid Chlorides: HYDROLYSIS • To avoid an acid

21. 8 Preparation and Reaction of Acid Chlorides: ALCOHOLYSIS • Often acid chlorides are

21. 8 Preparation and Reaction of Acid Chlorides: AMINOLYSIS • Often acid chlorides are

21. 8 Preparation and Reaction of Acid Chlorides • Acid chlorides can also be

21. 8 Preparation and Reaction of Acid Chlorides • To stop the aldehyde from

21. 8 Preparation and Reaction of Acid Chlorides • Two equivalents of the Grignard

21. 8 Preparation and Reaction of Acid Chlorides • The Gilman reagent is another

21. 8 Preparation and Reaction of Acid Chlorides • Figure 21. 9 illustrates the

21. 8 Preparation and Reaction of Acid Chlorides • Fill in necessary reagents for

21. 9 Preparation and Reactions of Acid Anhydrides • Acetic anhydride can be synthesized

21. 9 Preparation and Reactions of Acid Anhydrides • A more practical synthesis occurs

21. 9 Preparation and Reactions of Acid Anhydrides • Given that they both contain

21. 9 Preparation and Reactions of Acid Anhydrides • Figure 21. 10 shows how

21. 9 Preparation and Reactions of Acid Anhydrides • Acetic anhydride is often used

21. 9 Preparation and Reactions of Acid Anhydrides • Practice with conceptual checkpoint 21.

21. 10 Preparation of Esters • Fischer esterification combines a carboxylic acid an alcohol

21. 10 Preparation of Esters • Fischer esterification mechanism continued • Each step is

21. 10 Preparation of Esters • The overall Fischer esterification reaction is an equilibrium

21. 10 Preparation of Esters • Esters can also be prepared by treating an

21. 11 Reactions of Esters • Esters can undergo hydrolysis in the presence of

21. 11 Reactions of Esters • Esters can also undergo aminolysis • The overall

21. 11 Reactions of Esters • Esters can be reduced using reagents such as

21. 11 Reactions of Esters • Li. Al. H 4 is a strong reducing

21. 11 Reactions of Esters • Esters can also react with LAH • Two

21. 11 Reactions of Esters • Esters can also react with Grignard reagents •

21. 11 Reactions of Esters • Give necessary reagents for the conversions below Copyright

21. 12 Preparation and Reactions of Amides • Nylon is a polyamide • Polyester

21. 12 Preparation and Reactions of Amides • Amides can be hydrolyzed with H

21. 12 Preparation and Reactions of Amides • Li. Al. H 4 can reduce

21. 12 Preparation and Reactions of Amides • The iminium is reduced with a

21. 13 Preparation and Reactions of Nitriles • When a 1° or 2° alkyl

21. 13 Preparation and Reactions of Nitriles • What base might you use? Copyright

21. 13 Preparation and Reactions of Nitriles • An aqueous strong acid solution can

21. 13 Preparation and Reactions of Nitriles • Basic hydrolysis of a nitrile can

21. 13 Preparation and Reactions of Nitriles • Nitriles can also react with Grignards

21. 13 Preparation and Reactions of Nitriles • Similar to how carboxylic acids can

21. 14 Synthetic Strategies • When designing a synthesis, there are two general considerations

21. 14 Synthetic Strategies • Give necessary reagents for the conversion below. Multiple steps

21. 14 Synthetic Strategies • There are 2 categories of bond-forming reactions Copyright ©

21. 14 Synthetic Strategies • When forming new carbon-carbon bonds, it is critical to

Additional Practice Problems • Give an appropriate name for the compound below Copyright ©

Additional Practice Problems • Rank the following molecules by increasing p. Ka values. Copyright

Additional Practice Problems • Predict the products for the reactions below. Copyright © 2015

Additional Practice Problems • Give an appropriate name for the amide below Copyright ©

Additional Practice Problems • Using induction, sterics, and resonance, explain why acid halides are

Additional Practice Problems • Using the quality of the leaving group, explain why acid

Additional Practice Problems • Give reagents necessary for the synthesis below where all carbon

Slides: 96

Download presentation

21. 3 Structure and Properties of Carboxylic Acids • In water, the equilibrium generally favors the acid • p. Ka values mostly range between 4 and 5. What is p. Ka? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -3 Klein, Organic Chemistry 2 e

21. 3 Structure and Properties of Carboxylic Acids • How does the p. Ka value for a carboxylic acid compare to a strong acid like HCl or a very weak acid like ethanol? H-Cl p. Ka = -7 • How can induction and resonance be used to explain the acidity of a carboxylic acid? • Practice with conceptual checkpoints 21. 4 through 21. 7 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -4 Klein, Organic Chemistry 2 e

21. 4 Preparation of Carboxylic Acids • In earlier chapters, we have already learned some methods to synthesize carboxylic acids Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -6 Klein, Organic Chemistry 2 e

21. 4 Preparation of Carboxylic Acids • Let’s examine two more ways to make carboxylic acids 1. The hydrolysis of a nitrile can produce a carboxylic acid – The mechanism will be discussed later – Carboxylic acids can be made from alkyl halides using a twostep process Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -8 Klein, Organic Chemistry 2 e

21. 4 Preparation of Carboxylic Acids • Let’s examine two more ways to make carboxylic acids 2. Carboxylation of a Grignard reaction can be achieved using CO 2 -Mg. Br – The Grignard reagent and the H 3 O+ can not be added together. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -9 Klein, Organic Chemistry 2 e

21. 4 Preparation of Carboxylic Acids • This gives us a second method to convert an alkyl halide into a carboxylic acid • Practice with conceptual checkpoint 12. 10 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -10 Klein, Organic Chemistry 2 e

21. 5 Reactions of Carboxylic Acids • Li. Al. H 4 is a strong reducing agent that can convert an acid to a primary alcohol • The LAH acts as a base first • Then, an aldehyde is produced Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -12 Klein, Organic Chemistry 2 e

21. 5 Reactions of Carboxylic Acids • Li. Al. H 4 is a strong reducing agent that can convert an acid to a primary alcohol • The aldehyde is further reduced to the alcohol • Can the reduction be stopped at the aldehyde? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -13 Klein, Organic Chemistry 2 e

21. 5 Reactions of Carboxylic Acids • The more mild borane reagent can also be used to promote the reduction • Reduction with borane is selective compared to LAH reduction • Practice with conceptual checkpoint 21. 11 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -14 Klein, Organic Chemistry 2 e

21. 6 Introduction to Carboxylic Acid Derivatives • When Z is a heteroatom, the compound is called a carboxylic acid derivative • Because it has the same oxidation state, a nitrile is also an acid derivative despite not having a carbonyl group Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -16 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Carboxylic acid derivatives have electrophilic sites • Where? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -17 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Reactivity can be affected by – – Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -18 Induction Resonance Sterics Quality of leaving group Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Let’s examine the acid chloride – The electronegative chlorine enhances the electrophilic character of the carbonyl. HOW? – There are 3 resonance contributors to the acid chloride – The chlorine does not significantly donate electron density to the carbonyl. HOW does that affect its quality as an electrophile Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -19 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Let’s examine the acid chloride – Describe how the presence of the chloride affects the sterics of the nucleophilic attack on the carbonyl – The chloride is a good leaving group, which also enhances its reactivity • Considering all of the factors involved, the acid chloride is quite reactive Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -20 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Amides are the least reactive acid derivative • Examine the factors below to explain amide reactivity – Induction – Resonance – Sterics – Quality of leaving group Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -21 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Aldehydes and ketones are also electrophilic, but they do not undergo substitution • WHY? Consider induction, resonance, sterics, and quality of leaving group Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -22 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Nucleophilic acyl substitution is a two-step process • Because C=O double bonds are quite stable, the “loss of leaving group” step should occur if a leaving group is present • – H and –R do not qualify as leaving groups. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -23 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Let’s analyze a specific example • The highest quality leaving group leaves the tetrahedral intermediate Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -24 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Do NOT draw the acyl substitution with an SN 2 mechanism • Sometimes a proton transfer will be necessary in the mechanism – Under acidic conditions, (–) charges rarely form. WHY? – Under basic conditions, (+) charges rarely form. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -25 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Neutral nucleophiles are generally less reactive, but they can still react if given enough time • An intermediate with both (+) and (-) charge forms • Intermediates with two (+) or two (-) charges are very unlikely to form. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -26 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Depending on reaction conditions, up to 3 proton transfers may be necessary in the mechanism • Draw a complete mechanism for the reaction below • Will the reaction be reversible? • What conditions could be employed to favor products? • Practice with Skill. Builder 21. 1 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -27 Klein, Organic Chemistry 2 e

21. 7 Reactivity of Carboxylic Acid Derivatives • Give necessary reaction conditions and a complete mechanism for the reaction below • Describe how conditions could be modified to favor the products as much as possible Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -30 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides • Acid chlorides have great synthetic utility. WHY? • An acid chloride may form when an acid is treated with SOCl 2 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -31 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides • The mechanism is more favored in the presence of a non-nucleophilic base like pyridine. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -33 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides: HYDROLYSIS • To avoid an acid chloride being converted into an acid, it must be protected from moisture Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -34 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides: ALCOHOLYSIS • Often acid chlorides are used to synthesize esters • Give a complete mechanism showing how pyridine acts as a base in the mechanism Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -35 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides: AMINOLYSIS • Often acid chlorides are used to synthesize amides • Give a complete mechanism showing WHY two equivalents are used Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -36 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides • Acid chlorides can also be reduced using LAH • The acid must be added after the LAH has given adequate time to react completely Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -39 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides • To stop the aldehyde from being reduced to the alcohol, a bulky reducing agent can be used • HOW does lithium tri(t-butoxy) aluminum hydride allow the reduction to be stopped at the aldehyde? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -40 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides • Acid chlorides can also be attacked by Grignard nucleophiles Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -41 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides • The Gilman reagent is another nucleophilic organometallic reagent that reacts readily with acid chlorides • The C-Cu bond is less ionic than the C-Mg bond. WHY? Gilman reagent R • How does the ionic character of the bond affect the reactivity of the organometallic reagent? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -43 Klein, Organic Chemistry 2 e

21. 8 Preparation and Reaction of Acid Chlorides • Figure 21. 9 illustrates the reactions of acid chlorides we discussed • Practice with conceptual checkpoints 21. 18 through 21. 20 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -44 Klein, Organic Chemistry 2 e

21. 9 Preparation and Reactions of Acid Anhydrides • Acetic anhydride can be synthesized by heating 2 moles of acetic acid • Why is so much heat needed to drive the equilibrium forward? • This process doesn’t work for most other acids, because their structures can not withstand such high temperatures Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -47 Klein, Organic Chemistry 2 e

21. 9 Preparation and Reactions of Acid Anhydrides • A more practical synthesis occurs when an acid chloride is treated with a carboxylate • The –R groups attached to the anhydride do not have to be equivalent Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -48 Klein, Organic Chemistry 2 e

21. 9 Preparation and Reactions of Acid Anhydrides • Given that they both contain quality leaving groups, how do you think the reactions of anhydrides compare to the reactions we already saw for chlorides? • Which has a better leaving group? WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -49 Klein, Organic Chemistry 2 e

21. 9 Preparation and Reactions of Acid Anhydrides • Figure 21. 10 shows how anhydrides can undergo many reactions analogous to those of acid chlorides Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -50 Klein, Organic Chemistry 2 e

21. 9 Preparation and Reactions of Acid Anhydrides • Acetic anhydride is often used to acetylate an amine or an alcohol Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -51 Klein, Organic Chemistry 2 e

21. 10 Preparation of Esters • Fischer esterification combines a carboxylic acid an alcohol using an acid catalyst Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -56 Klein, Organic Chemistry 2 e

21. 10 Preparation of Esters • Fischer esterification mechanism continued • Each step is an equilibrium • Under acidic conditions, (-) charges are avoided Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -57 Klein, Organic Chemistry 2 e

21. 10 Preparation of Esters • The overall Fischer esterification reaction is an equilibrium process • How might you use Le Chatelier’s principle to favor products? • How might you use Le Chatelier’s principle to favor reactants? • Is there an entropy difference that might be exploited? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -58 Klein, Organic Chemistry 2 e

21. 10 Preparation of Esters • Esters can also be prepared by treating an acid chloride with an alcohol – see section 21. 8 • Practice with conceptual checkpoint 21. 22 and 21. 23 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -59 Klein, Organic Chemistry 2 e

21. 11 Reactions of Esters • Esters can undergo hydrolysis in the presence of aqueous hydroxide (saponification) • Predict the last steps in the mechanism • To produce a carboxylic acid, H 3 O+ must be added at the end. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -62 Klein, Organic Chemistry 2 e

21. 11 Reactions of Esters • Esters can also undergo aminolysis • The overall equilibrium favors the amide formation – Because of enthalpy or entropy? • The synthetic utility is limited, because the process is slow and because there are more efficient ways to synthesize amides Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -63 Klein, Organic Chemistry 2 e

21. 11 Reactions of Esters • Esters can be reduced using reagents such as Li. Al. H 4 • Two equivalents of reducing agent are required • Two alcohols are produced • Draw a reasonable mechanism Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -64 Klein, Organic Chemistry 2 e

21. 11 Reactions of Esters • Li. Al. H 4 is a strong reducing agent, so a full reduction beyond the aldehyde to the alcohol can not be avoided • When performed at low temperature, reduction with DIBAH yields an aldehyde. HOW? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -65 Klein, Organic Chemistry 2 e

21. 11 Reactions of Esters • Esters can also react with LAH • Two moles can be used to make a tertiary alcohol Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -66 Klein, Organic Chemistry 2 e

21. 11 Reactions of Esters • Esters can also react with Grignard reagents • Two moles can be used to make a tertiary alcohol • Practice with conceptual checkpoint 21. 24 and 21. 25 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -67 Klein, Organic Chemistry 2 e

21. 12 Preparation and Reactions of Amides • Amides can be hydrolyzed with H 3 O+, but the process is slow and requires high temperature • The mechanism is very similar to that for the hydrolysis of an ester • Show a complete mechanism • WHY is the process generally slow? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -71 Klein, Organic Chemistry 2 e

21. 12 Preparation and Reactions of Amides • Amides can be hydrolyzed with H 3 O+, but the process is slow and requires high temperature • Should the equilibrium favor reactants or products? WHY? • Where does the NH 4+ come from? • Amide hydrolysis can also be promoted with Na. OH, although the process is very slow Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -72 Klein, Organic Chemistry 2 e

21. 12 Preparation and Reactions of Amides • Li. Al. H 4 can reduce an amide to an amine • The mechanism is quite different from the others we have seen in this chapter • When the H- attacks, which is the best leaving group? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -73 Klein, Organic Chemistry 2 e

21. 12 Preparation and Reactions of Amides • The iminium is reduced with a second equivalent of hydride • Practice with conceptual checkpoints 21. 26 through 21. 28 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -74 Klein, Organic Chemistry 2 e

21. 13 Preparation and Reactions of Nitriles • When a 1° or 2° alkyl halide is treated with a cyanide ion, the CN- acts as a nucleophile in an SN 2 reaction • Nitriles can also be made by dehydrating an amide using a variety of reagents including SOCl 2 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -76 Klein, Organic Chemistry 2 e

21. 13 Preparation and Reactions of Nitriles • An aqueous strong acid solution can be used to hydrolyze a nitrile • In the mechanism, the nitrogen is protonated multiple times and water acts as a nucleophile • Draw a complete mechanism Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -78 Klein, Organic Chemistry 2 e

21. 13 Preparation and Reactions of Nitriles • Basic hydrolysis of a nitrile can also be achieved • Which group in the reaction acts as a nucleophile? • Which group acts to protonate the nitrogen? • Draw a complete mechanism Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -79 Klein, Organic Chemistry 2 e

21. 13 Preparation and Reactions of Nitriles • Nitriles can also react with Grignards • After the nitrile is consumed, H 3 O+ is added to form an imine, which can be hydrolyzed with excess H 3 O+ (aq) to form a ketone. SHOW a mechanism Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -80 Klein, Organic Chemistry 2 e

21. 13 Preparation and Reactions of Nitriles • Similar to how carboxylic acids can be converted to alcohols using LAH (section 21. 5), nitriles can be converted to amines • Practice with conceptual checkpoints 21. 29 through 21. 31 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -81 Klein, Organic Chemistry 2 e

21. 14 Synthetic Strategies • When designing a synthesis, there are two general considerations that we make 1. Is there a change in the carbon skeleton? 2. Is there a change in functional groups? • We have learned many new functional group transformations in this chapter – see next slide • Practice with Skill. Builder 21. 2 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -82 Klein, Organic Chemistry 2 e

21. 14 Synthetic Strategies • Give necessary reagents for the conversion below. Multiple steps will be necessary Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -84 Klein, Organic Chemistry 2 e

21. 14 Synthetic Strategies • When forming new carbon-carbon bonds, it is critical to install functional groups in the proper location • Give necessary reagents for the conversion below. More than one step will be necessary • Practice with Skill. Builder 21. 3 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -86 Klein, Organic Chemistry 2 e

Additional Practice Problems • Using induction, sterics, and resonance, explain why acid halides are especially electrophilic from a kinetic perspective. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -94 Klein, Organic Chemistry 2 e

Additional Practice Problems • Using the quality of the leaving group, explain why acid halides are especially reactive from a thermodynamic perspective. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -95 Klein, Organic Chemistry 2 e

Additional Practice Problems • Give reagents necessary for the synthesis below where all carbon atoms in the product come from a molecule of the reactant Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 21 -96 Klein, Organic Chemistry 2 e