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Transcript
OXIDATIVE PREPARATION OF ALDEHYDES AND KETONES REMEMBER: •Go back to Special Topics Box at the beginning of Chapter 14. •Conversion of an alcohol to an aldehyde or ketone represents an oxidation (removal of H atoms). •Conversion of an aldehyde to a carboxylic acid is also an oxidation (addition of an O atom). •Oxidation can involve the addition of oxygen atoms or it can involve the removal of hydrogen atoms (dehydrogenation). Oxidations R CH2 OH O O C C R H O O C C R H R CH NOTE: A dehydrogenation is also a form of oxidation! OH C R' OH OH O R R R R' Oxidation of Primary Alcohols O O [O] R CH2 OH [O] R C H R C The aldehyde can be oxidized in a second step [O] represent an oxidation OH Oxidation of Secondary Alcohols OH O [O] R C H R R C R Oxidation of Tertiary Alcohols OH [O] R C R R NO REACTION Oxidation of Primary Alcohols with KMnO4 O O R CH2 OH KMnO4 heat R C H KMnO4 heat R C You can’t pull the aldehyde out of this reaction, so the only product is the carboxylic acid. OH Specifically... O R CH2 OH H2O + KMnO4 O C R K heat + KOH + MnO2 (brown precipitate) O O R C O + H3O+ R C OH + H2O •The aldehyde is formed as an intermediate, but it is unstable under the reaction conditions and cannot be isolated. •There is a color change that accompanies the reaction -- the purple solution (KMnO4) changes to a brown mud (MnO2) Primary alcohols are oxidized by atmospheric oxygen to aldehydes and carboxylic acids. O CH3 CH2 OH O2 CH3 C O H O2 This reaction is very slow. It is catalyzed by enzymes (Acetobacter) This is how wine turns to vinegar!!! CH3 C OH Oxidation of Primary Alcohols to Aldehydes • Requires less vigorous oxidation conditions. • We can try to remove the aldehyde from the reaction medium as quickly as it is formed – Generally, the aldehyde has a lower boiling point than either the corresponding alcohol or carboxylic acid • We can also try to find a milder oxidizing agent. Dehydrogenation over Copper O Copper metal R CH2 OH R C H + H2 200 - 300 °C •This reaction is generally done by passing the vapors of the alcohol through a tube furnace in a stream of inert carrier gas. •This is not a practical laboratory method -- it is better suited to industrial processes. •The reaction stops at the aldehyde stage -- no more removal of hydrogen can take place. Oxidation of Primary Alcohols with K2Cr2O7 O O R CH2 OH K2Cr2O7 H2SO4 R C H K2Cr2O7 H2SO4 R C + Cr OH 3+ •This reaction can also be done using CrO3 (chromic oxide) in sulfuric acid. •The aldehyde is distilled away from the reaction vessel as quickly as it is formed. If the aldehyde is not removed, it will suffer a second oxidation, and the product will be the carboxylic acid. • The acidic conditions keep the chromium in the Cr2O72state. • Potassium dichromate is not as powerful an oxidizing agent as is potassium permanganate • Sodium dichromate can be substituted for potassium dichromate -- it makes no difference. • There is a color change during the reaction. The orange color of the dichromate changes to the green of Cr3+ ion. • This is not the world’s greatest way to prepare an aldehyde! Dichromate Oxidation of Ethanol 3 CH3 CH2 OH + 2 Cr2O72- + 16 H+ Orange solution O 3 CH3 C OH + 4 Cr3+ + 11 H2O Green precipitate Secondary alcohols are oxidized to ketones OH R CH O 2Cr2O7 R R C R H2SO4 Here, it doesn’t really matter whether you use potassium permanganate, potassium dichromate, nitric acid, sodium hypochlorite (Bleach), or other oxidizing agents. Actually, it does matter, but here we are presenting the simple introduction! “Mechanism” of Oxidation O OH R C O R + CrO3 Cr OH O R H C R H O O Cr several OH CrO3H O O slow R C R C R H R H O H H O H H steps Cr3+ •The important point about the mechanism is that the loss of the alcohol C-H occurs during the rate-determining step. •What is not well understood is what happens to the chromium after the formation of the ketone. There is some sort of cascading down through a series of oxidation states, but no one is sure exactly how this happens. Which would react faster? OH OH R C H R or R C R D There is a primary isotope effect -- C-H bond-breaking occurs during the ratedetermining step! Tertiary alcohols are not oxidized Under acidic conditions, the only available reaction is dehydration. Let’s re-examine methods for oxidizing primary alcohols to aldehydes and secondary alcohols to ketones (and let’s try some modern reactions!) Oxidation of Secondary Alcohols OH R CH O R K2Cr2O7 H2SO4 R + Jones Oxidation C Cr R 3+ Example CH3 CH3 K2Cr2O7 H2SO4 O OH CH CH CH3 CH3 (-)-Menthol CH3 (-)-Menthone CH3 … but what if you want to make an aldehyde? •The problem is how to stop the oxidation at the aldehyde stage. •We need mild oxidizing conditions -- strong enough to do one 2-electron oxidation, but not strong enough to do the second 2-electron oxidation. •We can use the Jones oxidation (potassium dichromate and sulfuric acid) and try to distill the aldehyde out of the reaction vessel before it gets oxidized a second time. •Or, we can tinker with the oxidizing agent, to attenuate its properties -- i.e., we can try to “dial in” the power of the oxidizing agent to just the right level. •Which brings us to... Oxidation with Chromic Oxide and Pyridine OH R CH CrO3 . O N R R CH2Cl2 Sarett Oxidation C R The oxidizing reagent is a type of complex between the chromic oxide and the pyridine. CrO3 O N R CH2 OH R CH2Cl2 C H Preparation of an Aldehyde O CrO3 pyr CH CH CH2 OH Cinnamyl alcohol CH CH C CH2Cl2 Cinnamaldehyde Note that the reaction does not affect other functional groups. H Another useful reagent for oxidizing alcohols to aldehydes or ketones -- in good yield (!) -is pyridinium chlorochromate (PCC). The reagent is prepared by dissolving CrO3 in hydrochloric acid and then adding pyridine. The reagent precipitates as a solid, with the formula: . CrO3Cl pyr CrO3Cl N H The reagent is used in nearly stoichiometric ratios to perform oxidations under mild conditions. Because the reagent is mildly acidic, however, it may not be suitable for use with acid-sensitive compounds. Oxidation with Pyridinium Chlorochromate OH R CH O CrO3Cl . N R CH2Cl2 “PCC” Oxidation R C R Example O PCC CH3 (CH2)18 CH2 OH CH2Cl2 CH3 (CH2)18 C 92% yield H Example #2 CH3 CH3 PCC CH3 C CH3 OH CH2Cl2 CH3 C O CH3 97% yield Getting better! Example #3 PCC CH OH C CH2Cl2 100 yield WOW!!! O Notice how the other functional groups survive without being changed. CH3 HO CH2 CH2 C O CH CH C O CH3 CH3 PCC CH2Cl2 O H C CH3 CH2 C O CH CH CH3 83% yield C O CH3 CHANGE OF GEARS: •Aldehydes can be oxidized to carboxylic acids. •This oxidation can take place under very mild oxidizing conditions. •Aldehydes can be oxidized with such weak oxidizing agents as metal cations, especially: Ag+ Cu2+ The Tollens Test O O C R H + 2 Ag(NH3)2OH C R + + 2 Ag O NH4 silver mirror + H2O + NH3 This test is specific for aldehydes -- ketones will not react with silver ion. The Tollens test is important in carbohydrate chemistry, for proof of structure. These monosaccharides cyclize to form hemiacetals O H C H HO CH2 OH OH H C HO O H H OH H OH H OH H OH CH2 OH Glucose CH2 OH Fructose b-D-(+)-Glucopyranose OH H CH2 H O HO HO OH H H OHH Notice that this is a hemiacetal •The hemiacetal form is in equilibrium with the open-chain free aldehyde form (remember mutarotation?). •While in the free aldehyde form, glucose can reduce silver ion (give a silver mirror -a positive Tollens test). •Because it can reduce silver ion, glucose is considered a reducing sugar. b-D-(-)-Fructofuranose HO This is a hemiacetal O H HO H OH CH2OH OH H •Being a hemiacetal, the cyclic form of fructose is in rapid equilibrium with the open-chain, free ketone form •Therefore, fructose is also capable of reducing silver ion, and is thus classified a reducing sugar! Yeah, but…. •I thought you said that only aldehydes were capable of giving a positive Tollens test, and fructose is a ketone! •There is an exception: a-hydroxyketones also give a positive test! •Fructose is an a-hydroxyketone (go back and check out its structure). Maltose: A Disaccharide CH2OH H O OH H b CH2OH H H c O OH H H a OH O HO H OH Position (b) is now an acetal H OH Position (a) is still a hemiacetal Maltose is a reducing sugar Sucrose: A Disaccharide CH2OH O H H OH HO H a H CH2OH H b H H O OH O OH CH2OH OH H Both positions (a) and (b) are now acetals. Neither is in equilibrium with the open-chain free carbonyl form. Sucrose is a non-reducing sugar! What about a monosaccharide-ether (a glycoside)? OH H CH2 H O HO HO O CH3 H H OHH This is an acetal -- it is not in equilibrium with a free aldehyde form This is a non-reducing sugar How do hydride transfer (oxidation-reduction) reactions take place in biological systems? • We can’t use lithium aluminum hydride or pyridinium chlorochromate inside a living cell! • Any reagent has to be water-soluble, capable of being transported across cell membranes, and able to act in concert with an enzyme. Nicotinamide Adenine Dinucleotide NH2 H N H C N O N O N N CH2 O O H H H OH P O_ H OH O O P O CH2 O_ H H O H H OH OH NH2 •The reactive portion is the hydrogen attached to Carbon #4 of the pyridine ring (see previous slide) •NADH acts as a reducing agent by transfering a hydride from the C-4 position. Reduction of Acetaldehyde in Fermentation OH O CH3 C + H H CH3 C H H H H H O C C NH2 + N N R R NADH O + NAD NH2 Reduction of Pyruvic Acid in Muscle Tissue O O CH3 C C OH O OH H + CH3 C C OH H H H H O C C NH2 + N N R R NADH O + NAD NH2 A biological oxidation would take place as the reverse of the reactions shown.