Chapter 19 Aldehydes and Keton Ketones and Aldehyd Ketones and Aldehyd 4. Assemble the name alphabetically 3. Assign a locant (number) to each substituents 2. Identify the name of the substituents (side groups) 1. Identify and name the parent chain • Same procedure as with alkanes, alcohols, etc… • Four discrete steps to naming an aldehyde or ketone Nomenclature Nomenclature Nomenclature Nomenclature Nomenclature Nomenclature Physical Properties Preparing Aldehydes and K Preparing Aldehydes and K Preparing Aldehydes and K Preparing Aldehydes and K Preparing Aldehydes and K Preparing Aldehydes and K Preparing Aldehydes and K Nucleophilic Addition Rea • Aldehydes are generally more reactive towards nucleophiles than ket 1. Steric effects - aldehydes are less sterically hindered 2. Electronic effects - aldehyde has a larger δ+ on the carbonyl carbon: Nucleophilic Addition Rea • Weak nucleophiles may require acidic conditions to activate the ele (increase electrophilicity by protonating the carbonyl) in order for the to proceed. • Strong nucleophiles are sufficiently reactive and do not require acti the carbonyl group and can react under basic conditions. • Example: the Grignard reaction = strong nucleophile Nucleophilic Addition Rea Nucleophilic Addition Rea Nucleophilic Addition Rea Nucleophilic Addition Rea The Addition of Alcohols: Hemiacetals an Oxygen Nucleophile The Addition of Alcohols: Hemiacetals an The Addition of Alcohols: Hemiacetals an • Alcohols can attack ketones/aldehydes: • Acetal formation is an equilibrating process • Under acidic conditions, the ketone/aldehyde can react with 2 molecules o to form an acetal. Oxygen Nucleophile The Addition of Alcohols: Hemiacetals an Oxygen Nucleophile The Addition of Alcohols: Hemiacetals an The Addition of Alcohols: Hemiacetals an The Addition of Primary and Seconda The Addition of Primary and Seconda Nitrogen Nucleophile The Addition of Primary and Seconda The Addition of Primary and Seconda Cyanohydrin Formatio Cyanohydrin Formatio The Addition of Ylides: the Wittig R The Addition of Ylides: the Wittig R The Addition of Ylides: the Wittig Wittig Reactions Wittig Reactions Wittig Reactions Oxidation of Aldehyde The Baeyer-Villiger Oxid Note, the migratory aptitude is used to predict whether R or R’ mi The Baeyer-Villiger Oxid Review of Reactions Migratory aptitude: H > 3° alkyl > 2° alkyl ≈ phenyl > 1° alkyl > methyl. Baeyer-Villiger Oxidati Spectroscopic Analysis – IR Spectroscopic Analysis – IR • Protons neighboring carbonyl are weakly deshield by the carbonyl group, a appear +1 ppm downfield Spectroscopic Analysis – 1 Chapter 18 Aromatic Substitution Reac Electrophilic Aromatic Subs Halogenation • Using F2 or I2 does not work well: – Fluorination too violent to be practical – iodination is generally slow with low yields • Benzene can also undergo chlorination by using Cl2 instead of Br2 • In addition to FeBr3, aluminum tribromide could also be used as the Lewis for bromination of benzene: Halogenation Halogenation Halogenation The rate determining ste (RDS) is formation of th carbocation (step 1). Halogenation Sulfonation Sulfonation • Note the equilibrium that is formed and Le Chatelier’s principle • Sulfonation is sensitive to reagent concentration; it is a reversible proce Sulfonation • It is believed a nitronium ion (NO2+)is the active electrophile • Nitration occurs by using HNO3 as the source of the electrophile, and H acid catalyst: Nitration Nitration Nitration Friedel-Crafts Alkylati Friedel-Crafts Alkylati Friedel-Crafts Alkylati Friedel-Crafts Alkylati Friedel-Crafts Alkylati Friedel-Crafts Alkylati Friedel-Crafts Alkylatio Acyl group Friedel-Crafts Acylatio Friedel-Crafts Acylatio Friedel-Crafts Acylatio Friedel-Crafts Acylatio Note, the highly acidic conditions required for this reaction. • An acylation followed by a Clemmensen reduction is a good alternative • Some alkyl groups cannot be attached to a ring by Friedel Crafts alkylation rearrangements Friedel-Crafts Acylatio Note, the highly basic conditions required for this reaction. The Wolff-Kishner reduction is a complementary method for reducing a k hydrocarbon. The conditions involve treating the ketone with hydrazine elevated temperatures. The Wolff-Kishner Redu Friedel-Crafts Acylatio Synthetic Application Toluene reacts much faster than benzene. Th group is electron-donating, making the ring a nucleophile. Activating Groups There are three possible products: the nitro grou could be installed at the ortho, meta, or par positions. Activating Groups Activating Groups Activating Groups Activating Groups Electrophilic Aromatic Subs • The methoxy group donates electron density via resonance: • The methoxy group in anisole activates the ring 400 times more than benz Activating Groups Activating Groups Activating Groups Activating Groups Electrophilic Aromatic Subs Deactivating Groups Deactivating Groups Deactivating Groups Deactivating Groups Electrophilic Aromatic Subs Electrophilic Aromatic Subs Halogens: The Excepti Halogens: The Excepti Halogens: The Excepti Halogens: The Excepti Electrophilic Aromatic Subs • The directing effects of –CH3 and the –NO2 direct the bromine to the sa one product is obtained • The directing effects of all substituents attached to a ring must be consi EAS reaction Multiple Substituents NO2 group is or the stronger OH • IF the groups direct to different carbons, the stronger group will d directing effects Multiple Substituents 1. For a monosubstituted ring, the para product typically dominates, due t • Steric hindrance must be considered when more than one product is using these guidelines: Multiple Substituents 2. For 1,4 disubstituted rings, substitution will occur at the less sterically hin more than one site is favored by directing effects) • Steric hindrance must be considered when more than one product is p these guidelines: Multiple Substituents 3. For 1,3 disubstituted rings, substitution typically does not occur b existing substituents • Steric hindrance must be considered when more than one product is po these guidelines: Multiple Substituents Blocking Groups Multiple Substituents Synthesis Strategies Synthetic Strategies Synthetic Strategies Note how increasin number of EWGs the SNAr reaction facile (undergoes at conditions). Nucleophilic Aromatic Subs Nucleophilic Aromatic Subs 3. The leaving group must be positioned ortho or para to the withdrawi 2. The ring must possess a good leaving group (e.g. halide) ring must be electron poor) 1. The benzene ring must possess a strong electron-withdrawing grou to occur: • Three requirements must be met for Nucleophilic Aromatic Substitut Nucleophilic Aromatic Subs Elimination-Addition Elimination-Addition Elimination-Addition Benzyne: Nucleophilic Aromatic Subs Elimination-Addition Carboxylic Acids an Their Derivatives Introduction Carboxylic A Nomenclature of Carboxyli Nomenclature of Carboxyli Pentanedio Nomenclature of Carboxyli Lauric acid (C12H24) Nomenclature and Physical Pro Water-insoluble carboxylic acids dissolve in either aqueous sodium hydroxid sodium bicarbonate, but water-insoluble phenols dissolve in aqueous sodi but (except for some nitrophenols) do not dissolve in aqueous sodium bicarb Forming the carboxylate salt of a carboxylic acid can be used to purify car The pKa of a carboxylic acid is generally around 4. Therefore, NaOH or NaHC deprotonated carboxylic acids to form water soluble carboxylate salts. How have a pKa of ~10, and therefore are deprotated with NaOH, but not NaHCO3 Nomenclature and Physical Pro Structure & Properties of Car Spectroscopy of Carb. A Spectroscopy of Carb. A Spectroscopy of Carb. A Spectroscopy of Carb. A Preparation of Carboxylic This is a very mild and excellent way to oxidize aldehydes to carboxylic acid molecules, it may be advantageous to oxidize primary alcohols to the aldehy Ag2O-mediated oxidation to the carboxylic acid instead of using the follo harsh oxidations of the alcohol to the carboxylic acid. Preparation of Carboxylic Preparation of Carboxylic Preparation of Carboxylic Preparation of Carboxylic Preparation of Carboxylic Reactions of Carboxylic Reactions of Carboxylic Carboxylic Acid Derivati Acyl Substitution: Nucleophilic Ad Elimination at the Acyl Carbo Note , the reactivity correla the basicity of th group, such that weaker Brønst than RCO2⊖, weaker than RO is weaker than H2 Carboxylic Acid Derivati Naming Acid Halides Naming Acid Halides Naming Anhydrides Naming Anhydrides Naming Esters • Same rules apply if the ester is connected to carboxylic acid’s name with the suffix –ate • Esters are named by naming the alkyl group attached to the oxygen fol Naming Esters Naming Amides Naming Amides Naming Amides Naming Nitriles Reactivity of Carb. Acid Deri Reactivity of Carb. Acid Deri Reactivity of Carb. Acid Deri Nucleophilic Acyl Substit Acyl Chlorides The reaction mechanism involves a nucleophilic addition-elimination reacti Acyl Chlorides Acyl Chlorides Acyl Chlorides Carboxylic Acid Anhydri Alcoholysis of Acyl Chlor Aminolysis of Acyl Chlori Reduction of Acyl Chlori Synthesis of Aldehyde Stabile intermediate at low temperatures Synthesis of Aldehyde Reactions of Acid Chlori Reactions of Acid Chlori Reactions of Acyl Chlorides-S Preparation of Acid Anhyd Preparation of Acid Anhyd Reactions of Acid Anhydr Reactions of Acid Anhydr Acetylation of salicyl produces less gastroin issues and is more absorbed in the gu salicylic acid. Aspirin is a pro-dr salicylic acid (metabol the drug in the body). Reactions of Acid Anhydr Preparation of Ester Preparation of Ester Esters Preparation of Ester Preparation of Ester Reactions of Esters Reactions of Esters Esters Esters Reactions of Esters Esters Reactions of Esters Reactions of Esters Reactions of Esters Reactions of Esters Preparation of Amide Preparation of Amide Amides Note, one of the oxygen atoms is activated to be a good leaving grou a nucleophilic addition-elimination reaction can occur. Amides Amides Synthesis Strategies Amides Amides Amides Reactions of Amides a variety of reagents including SOCl2 or P2O5: • Nitriles can also be made by dehydration of a 1° amide using Preparation of Nitrile amide, and then Reactions of Nitriles Polyesters and Polyamides: Step-Growth The above sequence produces a polyester, because it is made up of linkages. Previously we learned about chain-growth polymers, where p occurs by radical chain reactions. Consider what would happen if the carboxylic acid was a dicarboxylic acid a (or amine) was a diol (or diamine). Each component is doubly functionalized react twice. Elongation of the chain produces a step-growth polymer. Polyesters and Polyamides: Step-Growth Polyesters and Polyamides: Step-Growth Study Guide for Mid-term 3 1. Aromatic substitution reactions • What is the electrophilic aromatic substitution (EAS) reaction? • Understand the mechanisms, conditions and limitations of four types of EAS reactions: o Halogenation o Sulfonation o Nitration o Friedel-Crafts Alkylation/Acylation • Understand the activating (Electron donating) and de-activating (Electron withdrawing) groups in disubstituted benzene. • Understand the ortho/para directors and meta directors o All activating groups are ortho/para directors, while most deactivating groups are meta directors o One exception: halogens are deactivating groups, but they are ortho/para directors • Need to know the common ortho/para directors and meta directors in slide 51. • In multi-substituted benzene, the directing effects of all substituents attached to a ring must be considered in an EAS reaction. o The stronger substituent will dominate the reaction site. o If all sites are possible, substitution will occur at the less sterically hindered site o For 1,3 disubstituted rings, substitution typically does not occur between the existing substituents o SO3H can be used as a blocking group to prevent the substitution at the para position. o Need to understand the synthetic strategies for disubstituted rings. • Nucleophilic Aromatic Substitution (SNAr) o The strong electron withdrawing group such as NO2 at the ortho or para position of the ring facilitates the SNAr reaction based on an additionelimination reaction mechanism. A good leaving group such as halide is needed. o If there is no strong electron withdrawing group in the ring, the SNAr reaction will occur at extreme conditions such as high temperature and high pressure. The benzyne intermediate will be generated under an elimination-addition mechanism. 2. Aldehydes and Ketones • Nomenclature of aldehydes and ketones • Physical properties of aldehydes and ketones such as boiling point • Preparation of aldehydes and ketones • Nucleophilic addition reactions to reduce carbonyl compounds to alcohols. • Understand the structure and reaction mechanism for hemiacetals and Acetals o The reactions are reversible o The acetals can be used as a protecting group for carbonyl groups to selectively reduce or oxidize the other functional groups. o Thioacetals can be used as a protecting group as well. • How to form imines and enamines from amines? (Understand the structure and reaction mechanisms) • Cyanohydrin formation and application • The Wittig reaction and Horner-Wadsworth-Emmons (HWE) reaction o Convert carbonyl compounds to alkenes • The Baeyer-Villiger Oxidation (Understand the mechasnim) • Spectroscopic Analysis – IR and 1H NMR Question 1 You have now studied eleven major organic reaction families. a) Acid base reactions b) Electrophile/nucleophile addition to alkenes c) Electrophilic aromatic substitution reactions d) Nucleophilic substitution reactions e) Elimination reactions Oxidation 9) Substitution at an acyl group h) Aldol condensation Claisen condensation Dimine formation k) Imine hydrolysis Identify the reaction family of each of the following: 1) OPP: 2) ca-ca- soos uloz met 31 NH Capsaicin pepper Question 5 Write out the mechanism of the following reaction. COA COA Base COA 'S + HSCOA
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