<p>Chapter 18 – Ketones and Aldehydes</p><p> Nomenclature</p><p> o Ketones have priority over alcohols</p><p>. Find the longest chain with the carbonyl in it.</p><p>. Name the parent and replace the “e” with “one”</p><p>. Say where the carbonyl is.</p><p>O</p><p> octan-3-one</p><p>. When the ketone is not the high-priority group, you call the carbonyl “oxo” to name it.</p><p>. Common names: Name the two pieces coming off the carbonyl and call it “ketone”</p><p>O</p><p> ethyl butyl ketone</p><p> o Aldehydes have priority over ketones</p><p>. Find the longest chain with the carbonyl at the end.</p><p>. Name the parent and replace the “e” with “al.”</p><p>O</p><p>O</p><p>3-oxo-octanal</p><p> Synthesis of ketones and aldehydes o Oxidation of alcohols</p><p>Chromic Acid KMnO4 PCC Swern 1° ROH RCOOH RCOOH RCHO RCHO 2° ROH Ketone Ketone Ketone Ketone 3° ROH NR NR NR NR</p><p> o Ozonolysis of alkenes </p><p>1) O3 O</p><p>2) DMS O</p><p>. See Chapter 8 for review</p><p> o Friedel-Crafts Acylation</p><p>O O</p><p>Cl</p><p>AlCl3</p><p>. See Chapter 17 for review</p><p> o Hydration of alkynes</p><p>. Acid-catalyzed</p><p>H2SO4 (aq) H HgSO4 O</p><p>. Hydroboration-oxidation</p><p>O 1) Sia2BH H - 2) H2O2, OH</p><p>. See Chapter 8 for review o Synthesis from carboxylic acids and acid chlorides</p><p>. Acids are first converted to acid chlorides.</p><p>O O SOCl2 OH Cl</p><p>. Acid chlorides are reduced to aldehydes with LiAlH(OtBu)3</p><p>O O 1) LiAlH(OtBu)3</p><p>Cl 2) H2O</p><p> LiCuR2</p><p> o LiCuR2 is like a specialty version of a Grignard that only replaces the Cl of acid chlorides.</p><p>O O</p><p>LiCu(CH2CH3)2 Cl</p><p> Wittig Reactions</p><p> o Overall reaction: turn a carbonyl into a carbon-carbon double bond.</p><p>. The carbon of the alkyl halide replaces the oxygen of the carbonyl.</p><p>O</p><p>Br Ph3P BuLi</p><p>CH3</p><p> o Step one: Triphenylphosphine attacks an alkyl halide</p><p>H Ph + Ph ·· CH3 P H Ph P Br Ph Ph Ph H</p><p> o Step two: Grignard deprotonates to form the ylide . What’s an ylide?</p><p> An ylide is when you have two atoms next to each other where one has a negative charge, the other has a positive charge, and they both have full octets.</p><p>Ph H Bu Li Ph + + - P H P H Ph Ph H Ph H Ph o Step 3: ylide attacks the carbonyl</p><p>Ph Ph + Ph3 P – O O Ph P +</p><p>- H H o Step 4: O- forms bond with P+</p><p>Ph3</p><p>+ P Ph3 P – O O</p><p> o Ring collapses – fun with arrows</p><p>Ph3</p><p>H H H P O H o Considerations: You want alkyl halide to be methyl or primary because they are best for </p><p>SN2</p><p> Hydration</p><p> o Acid-catalyzed</p><p>H H + O + O + OH H OH O OH H</p><p>H2O</p><p> o Base-catalyzed</p><p>O OH – OH OH O H2 O</p><p>-OH</p><p> o Rates</p><p>. This reaction doesn’t happen to a large degree with most ketones</p><p>. It happens a little more with aldehydes</p><p>. Keq for formaldehyde is 40</p><p> Formation of Cyanohydrins</p><p> o HCN is a toxic gas, so most often it is made in situ from excess NaCN and HCl.</p><p> o Step one: cyanide ion attacks the carbonyl.</p><p>O CN – O</p><p>-CN</p><p> o Step two: protonation</p><p>CN – CN O H--CN OH o Things you can do with cyanohydrins.</p><p>. Catalytic hydration</p><p>H H H H N O O CN H2/Pt</p><p>. Hydrolysis</p><p>H H O + O + H3O NH4 CN COOH +</p><p> Formation of imines</p><p> o Overall: The nitrogen replaces the oxygen of the carbonyl, forming a carbon- nitrogen double bond.</p><p>. It should be mildly acidic; pH between 4 and 5.</p><p>H O N + NH3, H</p><p> o Mr. Baker said that you are not responsible for the mechanism, but here it is in case you want to look at it.</p><p> o Step one: protonation of the carbonyl</p><p>H O O+ H+</p><p> o Step two: Amine attacks the activated carbonyl H H + O OH H + N H</p><p>H ·· H N</p><p>H o Step three: Deprotonation</p><p>H H OH H + OH N N H H</p><p> o Step four: Protonation of hydroxyl</p><p>H H H + H+ OH OH N N H H</p><p> o Step five: Loss of water</p><p>H H H H + H H OH N+ N N: H + o Step six: Deprotonation</p><p>H H H + N N  Formation of acetals</p><p> o You could call an acetal a geminal diether</p><p>. A hemiacetal is what you have when you’re halfway there.</p><p>. It is one hydroxyl and one alkoxy group coming off the same carbon.</p><p> o Step one: protonation of the carbonyl</p><p>H O O+ H+</p><p> o Step two: the alcohol attacks the activated carbonyl</p><p>H H O+ H O O+</p><p>O H</p><p> o Step three: deprotonation to give the hemiacetal</p><p>H</p><p>+ H O O H O O</p><p> o Step four: Protonation of the hydroxyl</p><p>H H+ + H O O H O O o Step five: water falls off</p><p>H + H O O + O</p><p> o Step six: another alcohol adds</p><p>H O+ + O O</p><p>O H</p><p> o Step seven: deprotonation gives the acetal</p><p>H + O O O O</p><p> Removing acetals</p><p> o Use very dilute acid</p><p> o The mechanism of hydrolysis of an acetal is just the same thing going backwards.</p><p> Acetals and hemiacetals in sugars</p><p> o Sugars exist in their cyclic forms as hemiacetals . The carbon which is the hemiacetal or acetal is called the anomeric carbon.</p><p>. When the OH is up, it’s Beta; when it’s down, it’s alpha.</p><p>OH</p><p>OH O OH OH</p><p> anom eric carbon OH</p><p> o When they link up to become polysaccharides, they become acetals.</p><p>OH</p><p>OH O OH</p><p>O OH OH O OH OH</p><p>OH</p><p> o Something you don’t need to know for this class, but the MCAT expects you to know:</p><p>. Sugars that differ by only one chiral center are called epimers.</p><p>CHO CHO</p><p>H OH H OH H OH HO H H OH H OH H OH H OH</p><p>CH2OH CH2OH</p><p>D-allose D-glucos e</p><p> Protecting groups</p><p> o Requirements of a good protecting group</p><p>. Easy to put on . Nonreactive under the reaction conditions</p><p>. Easily removable</p><p> Oxidation of aldehydes</p><p> o Aldehydes are oxidized to carboxylic acids by KMnO4 and chromic acid</p><p> Reductions of ketones and aldehydes</p><p> o The following reductions which have already been seen work on ketones and aldehydes:</p><p>NaBH4 LiAlH4 H2/ Raney Zn(Hg)/HCl N2H4/base Ni (aq)</p><p>Ketone 2° ROH 2° ROH 2° ROH Alkane Alkane</p><p>Aldehyde 1° ROH 1° ROH 1° ROH Alkane Alkane</p>