CHM 222 Chap 18-21

• Chapter 17 introduces carbonyls, functional carbonyl groups, and general reactions of these groups
• Subsequent chapters focus on specific carbonyl groups and their reactions
• Repetition in the textbook chapters is minimized

Aldehydes and Ketones

• Aldehydes contain at least one H atom bonded to the carbonyl carbon
• Ketones have two alkyl or aryl groups (or a combination) bonded to the carbonyl carbon
• Reactivity towards nucleophiles increases in the order: ketone < aldehyde
• Steric hindrance increases in the order: aldehyde < ketone

Common Names of Aldehydes

• C atom numbers 1-6 have respective parent names form-, acet-, propion-, butyr-, valer-, and capro-
• A benzene ring has a parent name benz-

Common Names of Ketones

• Naming involves naming both groups on the carbonyl carbon alphabetically and adding "ketone"
• IUPAC name for ethyl methyl ketone is butan-2-one
• Widely used common names for simple ketones that do not follow the convention: acetone, acetophenone, benzophenone

Preparation of Aldehydes

• Oxidation of primary (1°) alcohols by PCC yields aldehydes
• Reduction of esters using DIBAL-H followed by H₂O will yield aldehydes
• Reduction of acid chlorides using LiAlH[OC(CH₃)₃]₃ followed by H₂O will yield aldehydes
• Hydroboration-oxidation of an alkyne using R₂BH followed by H₂O₂, ⁻OH yields aldehydes

Preparation of Ketones

• Oxidation of secondary (2°) alcohols with Cr⁶⁺ reagents (CrO₃, Na₂Cr₂O₇, K₂Cr₂O₇, PCC) yields ketones
• Friedel-Crafts acylation leads to the production of ketones
• Oxidative cleavage of alkenes (ozonolysis) is another method to make ketones and aldehydes

General Reactions

• Reaction at the carbonyl carbon involves adding H and Nu to the carbonyl group
• Reaction at the α carbon involves enolates reacting as nucleophiles with electrophiles (E⁺) to form new bonds

Nucleophilic Addition Reactions

• Specific examples of nucleophilic addition are outlined in Figure 18.4
• Chapter 17 reduction and organometallic reactions are key

Carbonyl Group Formation

• Treating an aldehyde or ketone with NaCN and a strong acid (HCl) adds HCN across the C=O π bond
• Forming a cyanohydrin, establishing a new carbon-carbon bond
• CN can be changed to a CO group

Wittig Reaction

• The Wittig reaction uses a carbon nucleophile from a Wittig reagent to form alkenes from carbonyl groups
• A Wittig reaction forms two new carbon-carbon bonds via one new σ bond and one new π bond
• Also forms a phosphorus by-product of Ph₃P=O (triphenylphosphine oxide)

Wittig Reagent

• Wittig reagent is an organophosphorus reagent with a phosphorus atom bonded to three phenyl groups and an alkyl group with a negative charge
• Ylide is a species where two oppositely charged atoms are bonded to each other, with both atoms having octets
• Phosphorus is a second-row element and can be surrounded by more than eight electrons
• A second resonance structure can be drawn between carbon and phosphorus
• One resonance structure shows the carbon bearing a negative charge

Results of Wittig Reagents

• The overall result is oxygen replacement by CRR' and R and/or R' can be H, alkyl, aryl (combinations)

Drawbacks of Wittig Reagents

• One limitation of the Wittig reaction is that a mixture of steroisomers sometimes forms

Retro Synthesis via Wittig Reagents

• What starting materials are needed to synthesize alkene X
• Cleave the carbon-carbon double bond into two components
• Add "O" to one side
• Add "Ph₃ " to other

Additional Information

• Wittig reaction to synthesize alkenes always favors a single constitutional isomer in comparison to grignard
• Derivatives of aldehydes and ketones: imines, enamines, gemdiols, acetals, hemiacetals

Chapter 19: Carboxylic Acids

• Slides concentrate on reactions, mechanisms, and concepts
• This chapter has some previous discussions of carbonyls that will not be repeated

Carboxylic Acids

• Contain the carboxy group (COOH), abbreviated as RCOOH or RCO₂H

Nomenclature

• Carboxylic acids are identified by a suffix added to the parent name of the longest chain with different endings
• Endings depend on whether the carboxy group is bonded to a chain or a ring
• If the group is on a chain, then the longest chain ends with "oic acid"
• Examples from the text: (acetic acid, formic acid, hexanoic acid)
• If the COOH is bonded to a ring, name the ring and add the words "carboxylic acid”
• Diacids are named as "dioic acid (2 COOH groups)

Metal Salts

• Metal salts of the acid contain the metal with an "ate" suffix at the end of the name

Carboxylic Acid Synthesis

• Oxidation of 1° alcohols (Section 12.12B)
• Oxidation of aldehydes (Section 17.8)
• Carboxylation of Grignard reagents (Section 17.14)
• Oxidation of alkyl benzenes (Section 16.15A)
• Oxidative cleavage of alkynes (Section 12.11)

Ozone Use

• Use of ozone in oxidative cleavage of alkenes, see chapt 18 From Chapt 18
• Use of ozone in synthesis from alkynes (Chapter 12.11), oxidative cleavage of all bonds of the triple bond

Synthesis from Alkyl Arenes

• Arenes containing at least one benzylic C-H bond are oxidized with KMnO4 to benzoic acid

Oxidation of Alcohols

• Primary alcohols are oxidized to either aldehydes or carboxylic acids by replacing either one or two C-H bonds by C-O bonds. (chapter 12.12b)
• Secondary alcohols are oxidized to ketones by replacing one C-H bond with a C-O bond
• Tertiary alcohols have no H atoms on the carbon with the OH group, so they are not easily oxidized

Oxidation Reagents

• Primary alcohols can be oxidized to carboxylic acids using strong reagents
• Na₂Cr₂O₇, K₂Cr₂O₇, or CrO₃ in the presence of H₂O and H₂SO₄

Reactions

• Carboxylic acids are strong organic acids and readily react with Brønsted–Lowry bases to form carboxylate anions

Common Deprotonation Bases

• Common Bases Used to Deprotonate Carboxylic Acids as outlined in Table 19.4

Substituent Effects on Acidity

• Substituents on a benzene ring donate or withdraw electron density, determining the acidity of substituted benzoic acids
• Electron-donating groups destabilize a conjugate base, making an acid less acidic
• Electron-withdrawing groups stabilize a conjugate base, making an acid more acidic

Common Substituents

• Common substituents affect the reactivity of a benzene ring towards electrophiles and the acidity of substituted benzoic acids (Figure 19.7)
• Groups that donate electron density activate a benzene ring towards electrophilic attack and make a benzoic acid less acidic
• Groups that withdraw electron density deactivate a benzene ring towards electrophilic attack and make a benzoic acid more acidic

Chapter 20: Carboxylic Acid Derivatives

• Functionality leads to other functionalities
• Awareness of functional groups is important
• Mechanisms in this chapter will selected

Introduction and Definition

• Carboxylic acid functionality is important because it leads to other types of functionalities via reactions
• Be aware of the different functional groups (there are several)
• Determine how they are synthesized (basic concepts)
• Concentration will be on the general reactions
• There are a large number of reactions and mechanisms in this chapter (only selected mechanisms will be discussed)
• Z = An atom more electronegative than carbon

Resonance Structures

• Three resonance structures stabilize carboxylic acid derivatives (RCOZ)
• As resonance structures 2 and 3 contribute to the resonance hybrid, the more stable RCOZ becomes
• The more basic Z is, the more it donates its electron pair, and the more resonance structure 3 contributes to the hybrid.

Basicity and stability

• As the basicity of Z increases, stability of RCOZ increases because of added resonance stabilization
• So the amides are less reactive than the other groups.

Nucleophilic Acyl Substitution

• Z can be a leaving group in nucleophilic acyl substitutions

General Nu Reactions

• Reaction occurs with both negatively charged nucleophiles and neutral nucleophiles
• Carboxylic acid derivatives (RCOZ) react with nucleophiles because they contain an electrophilic, unhindered carbonyl carbon
• Substitution occurs, not addition, because carboxylic acid derivatives (RCOZ) have a leaving group Z on the carbonyl carbon

Nucleophilic Acyl Substitution

• General mechanism

Steps of Substitution

• The nucleophile attacks the electrophilic carbonyl group
• The π bond is broken, moving an electron pair out on oxygen and forming an sp³ hybridized carbon
• An electron pair on oxygen re-forms the bond and Z comes off as a leaving group with the electron pair in the C-Z bond
• Nucleophiles that participate in this reaction include are Oxygen or Nitrogen nucleuphiles

Leaving Groups

• Nu replaces the leaving group

Rules

• For a reaction to occur, Z must be a better leaving group than Nu.

Reactivity and Leaving Group

• :Cl;
• Overall reactivity
• The final product is an amide

Steps of Reaction

• An acid chloride, having the best leaving group of acid derivatives
• HCl is usually formed as a product
• A weak base like pyridine is added to the reaction mixture to remove the strong acid (HCl)
• A pyridine ring removes the H on the new molecule, and a Cl bonds to the pyridine from the leaving group (HCl as a product)

Other Reactions

• Acid chlorides reacts with oxygen nucleophiles to form anhydrides, carboxylic acids, and esters

Acid Halides

• Acid chlorides react with ammonia and amines (primary, secondary, tertiary) to form amides (primary, secondary, tertiary, respectively)
• In this case a acid (halide) will leave, taking with it one of the Hydrogens on the first reactant
• This will create a unstable leaving group
• The 2nd halide will want to take a more stable atom, which is a H, therefore, it will want to find a hydrogen

Proton Removal

• For Carboxylic acids , nucleophiles as strong bases will remove a proton before any electrophilic substitution reaction can take place

Nucleophiles

• For a reaction with carboxylic acids, the nucleophile will first act as a base before the main reaction takes place (acid-base reaction)

Reactions

• Acyl substitution reactions of carboxylic acids

Acid Chlorides

• Treatment of a carboxylic acid with thionyl chloride (SOCI₂) affords an acid chloride

Fischer esterification

• The reaction of a carboxylic acid with an alcohol (needs catalyst)

The Elimination of Protons

• OH has to become good leaving group and step 2 has to be enacted

Presence of a Base

• Ester formation does not occur in the presence of a base
• Base removes a proton from the carboxylic acid, forming the carboxylate anion, and a poor leaving group
• Therefore, base cannot React with a nucleophile

Acidity and Making New Substances

• Each line represents what can be made with that material (doesn't tell what you need to add)

Chapter 21 Reactions on CARBONYL Groups

Primary Discussions

• Primarily concentrated on the reactions of Carbon
• Primarily if a H is of the reaction it is a reaction at the carbon
• Reactions can be determined by what atoms on the carbon
• This section focus primary on one hydrogen bonds

Enols and Enolates

• Carbons react by enolates and through use of Intermediates
• This reactions can be broken down into three steps:

1. Enol is introduced by alpha to Carbon bonding
2. A reaction with enolate the replaces H 3 .Interest and addition of the reaction replaces Enolate to alpha with Carbon boning

Carbon Bonds

• This reaction is determined by a base which removes a proton, removing a carbon
• The α carbon is less still acidic