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Transcript
Chemistry 2600 Lecture Notes Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Page 1 of 15 Addition Reactions of aldehydes and ketones; introduction to sugar chemistry • Next six chapters in the text deal with the carbonyl group (three to be covered in Chem2600) • This chapter deals with nucleophilic addition to aldehydes and ketones (only) • We start by reviewing what we have already learned in this course about carbonyl chemistry 1. Synthesis of carbonyl compounds was covered in Chapter 8: Type of alcohol Oxidation reaction Result H Primary R OH O [O] R Aldehydes under mild oxidation conditions H H H Primary R OH O [O] R Carboxylic acids under aggresive oxidation conditions O H H R' Secondary R OH O [O] R R' Ketones under all oxidation conditions, mild conditions generally prefered H R' Tertiary R OH [O] No reaction because no H to eliminate R'' Name of reagent Reagent/condition Result Swern Enzymes (alcohol dehydrogenase) • DMSO, ClCOCOCl ‚NEt3 NAD+ or NADP + “coenzyme” Collin’s reagent CrO 3 .py2 in CH2 Cl2 at R.T. Corey’s reagent PCC = (pyH+)(CrO 3 Cl)– Jones’ reagent (high valence Cr in acid condit.) MnO4 – (high valence Mn in base condit.) MnO2 (freshly prepared) CrO 3 in H2 SO4 = “H2 Cr2 O7 ” or CrO 3 in CH3 COOH • MnO4 – in H2 O, OH– ‚ H3 O+ (workup to release acid) MnO2 in acetone, R.T. or MnO2 in benzene, R.T. °1 ROH to aldehyde °2 ROH to ketone °1 ROH to aldehyde °2 ROH to ketone °1 ROH to aldehyde °2 ROH to ketone °1 ROH to aldehyde °2 ROH to ketone °1 ROH to carboxylic acids (°2 ROH to ketone – not best!)\ °1 ROH to carboxylic acids (°2 ROH to ketone – not best!)\ Allylic and benzylic alcohols only °1 ROH to aldehyde °2 ROH to ketone Chemistry 2600 Lecture Notes 2. Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Addition of organomagnesium, organolithium, organocopper and acetylides (Chapter 13) Grignard Reagents Page 2 of 15 Chemistry 2600 Lecture Notes 3. Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Reduction of addition products: Hydride Reduction Page 3 of 15 Chemistry 2600 Lecture Notes 4. Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Page 4 of 15 Hydrogen reduction of aldehydes and ketones • Metal-catalyzed addition of hydrogen to a double bond (p. 416) O • H H2, Pt OH Hydrogenolysis occurs for benzylic alcohols O H H H2, Pt 5. Zinc amalgam reduction of aldehydes and ketones 6. The Baeyer-Villager Oxidation • The conversion of a ketone to an ester using a peroxo-carboxylic acid, usually PTFA H O R R' H O3CCF 3 H + O R -:O O 3CCF3 R R' + O R H H O -:O CCF 2 3 O R R' • This differs from oxidations learned in Ch. 8. Why? O R' O O R' O CF3 Chemistry 2600 Lecture Notes • Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Page 5 of 15 Cyclic ketones lead to an important class of cyclic esters called LACTONES O O CF3CO3H Remember, CF3CO3H is of course: O O CF3 O O H “Migratory aptitude of R’ group” Aryl > 4° > 3° > 2° > 1° > Methyl • So for asymmetric ketones the following happens: O O CF3CO3H O AND O R • O CF3CO 3H CH3 R O CH3 R > one carbon Hydrolysis of the products leads to alcohols (e.g. ROH and acetic acid for above right) (see Chapter 19) • The conversion of an aldehyde to a carboxylic acid is another consequence of the Baeyer-Villager reaction. O CF3CO3H H O OH (this is not a new concept; just another way to oxidize aldehydes, p.355 to p.358) Chemistry 2600 Lecture Notes Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Nucleophilic addition reactions to aldehydes and ketones: Mechanism 1. • Order of reactivity of aldehydes and ketones: • Reason: Nucleophilic HCN addition under basic conditions gives a cyanohydrin There are two workup reactions indicatated: Page 6 of 15 Chemistry 2600 Lecture Notes Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones 2. Nucleophilic addition of HX form geminal halohydrins 3. Nucleophilic addition of Water: formation of “hydrates” or “Gem-diols” • Page 7 of 15 For most aldehydes and ketones, the hydrate is not stable, but there are important exceptions: Chemistry 2600 Lecture Notes 4. Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Page 8 of 15 Nucleophilic addition of alcohols: formation of Acetals (sometimes called Ketals) • Addition to aldehydes is always potentially a two-stage reaction: 1.) 2.) • Mechanism involves acid catalysis (a crucial mechanism, learn it well): • The same mechanism applies for the addition of thiols and dithiols Chemistry 2600 Lecture Notes • Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Addition to ketones is also two-stage but requires more forcing conditions A hemiacetal (older: hemiketal) An acetal (older: ketal) • The mechanism is the same as for addition to aldehydes • We met acetals in Chapter 13 as protecting groups for with alcohols and ketones Alcohol + vinylic ether Alcohol + a-chloroether Ketone + vicinal diol Page 9 of 15 Chemistry 2600 Lecture Notes 5. Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Page 10 of 15 Hemiacetals are the key to understanding the carbohydrates (“sugars”) • Ring-chain tautomerism of hemiacetals result in stable rings under special conditions • Stable rings are commonly seen among sugars Chain-glucose a-glucopyranose ß-glucopyranose Chemistry 2600 Lecture Notes Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones • Sugars are classified by the number of carbon atoms in the chain • There are three-carbon, four-carbon, five-carbon and six-carbon sugars • Sugars may be aldoses (contain an aldehyde) or ketoses (contain a ketone) Page 11 of 15 Chemistry 2600 Lecture Notes Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Molecular Modeling of Sugars – relation to Fischer and Haworth projections Page 12 of 15 Chemistry 2600 Lecture Notes Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones β-D-Glucopyranose • Page 13 of 15 α-D-Glucopyranose Take β-D-Glucopyranose, and place on its side, with CH2 OH group at bottom, then break bond to anomeric carbon, and open up the chain: Chemistry 2600 Lecture Notes Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones Sugar Chemistry • Acetal derivatives are made by addition of alcohol to aldose carbonyl groups • The alcohol can be from another sugar, producing di- and polysaccharides • Sucrose and Lactose are common disaccharides • Carbohydrates are polysaccharides: Amylose (starch) Cellulose • Polysacharides are hydrolysed to sugars under acid conditions because they are acetals Page 14 of 15 Chemistry 2600 Lecture Notes Chapter 17 Nucleophilic Addition Reactions of Aldehydes and Ketones • Reduction of the carbonyl groups of sugars produces alditols which are polyols • Oxidation of sugars leads to: carboxylic acids using aqueous Br2 • Such long-chain carboxylic acids can also cyclise to give cyclic esters (lactones) • With concentrated nitric acid, dicarboxylic acids also called aldaric acids are produced Page 15 of 15