Chapter 11

1 Chapter 11 Oxidation in Organic terms Oxidation Addition of O, X2; loss of H2 Reduction Addition of H2; loss of O or X2 Neither Anytime you oxidize one carbon but reduce another (ex. Adding H and OH to adjacent carbons) Oxidation of alcohols Chromic Acid KMnO4 PCC Swern 1 ROH RCOOH RCOOH RCHO RCHO 2 ROH Ketone Ketone Ketone Ketone 3 ROH NR NR NR NR Why don t you oxidize 3 alcohols? [O]5 bonds to carbon=crazy talk!OHO[O]5 bonds to carbon=crazy talk!OHO You won t need to draw the structure of PCC, but you do need to recognize it. pyridinium chlorochromate (PCC)CrOOClO N+Hpyridinium chlorochromate (PCC)CrOOClO N+H You don t need to know all the reagents of Swern Oxidation for Mr. Baker s class. Tollens Test Not tested in this course. o Qualitative test for aldehydes o Aldehyde + AgNO3 Carboxylic acid + silver metal o If you see the silver metal coating the tube, then you know you have an aldehyde.

2 NAD+/NADH o You need to know the structures of both! o NAD+ is the oxidized form/oxidizing agent H2sugarN+ONH2sugarN+ON o NADH is the reduced form/reducing agent NH2sugarNOHNH2sugarNOH Formation of Tosylates Ra sulfonyl chloridetosyl chloride(a specific sulfonyl chloride)SOOClSClOORa sulfonyl chloridetosyl chloride(a specific sulfonyl chloride)SOOClSClOO o Addition of tosyl chloride (TsCl) converts the hydroxyl into a good leaving group (-OTs) with retention of stereochemistry. -OTs is a weak base OHTsClOTsOHTsClOTs o Recognize that any sulfo nyl chloride will do this o You don t need to draw out the entire structure when you use tosyl chloride to make a tosylate You do need to draw out the entire structure when you use a different sulfonyl chloride to form a sulfonate. OHF3 COCF3 SOOClSOOOHF3 COCF3 SOOClSOO o The RSO3- is a very weak base, so it s an excellent leaving group.

3 O That s it! Don t stress out over this. Reacting with HX o The hydroxyl is protonated. Water falls off, leaving a carbocation intermediate HClO+HHOH+ Carbocations rearrange! HH++ o The halide ion attacks the carbocation. Cl ClH+ o With 1 alcohols, this reaction occurs through an SN2 mechanism. Specialty Reagents o PX3, PX5, and SOCl2 all replaced hydroxyl groups with halogens Sometimes you ll just see phosphorus and bromine (or P/I2) here. Think flexibly. It makes PBr3 (PI3). Don t worry about mechanism or stereochemistry here. SOCl2 works better than PCl3 and PCl5. o That s it! Dehydration of alcohols o Protonate the hydroxyl, water falls off, leaving a carbocation H2SO4H3PO4O+HHOH+H2SO4H3PO4O+HHOH+ o Eliminate in both directions + o Look to see if the original carbocation can rearrange H++ o Again, eliminate in all directions + Formation of symmetrical ethers industrial dehydration of alcohols H+O+HOHO+HHOHOH+O+HOHO+HHOHO o First, the hydroxyl group is protonated, creating a good leaving group.

4 O Then, another alcohol comes along and kicks off the water in an SN2 mechanism. o The reaction is finished off with the deprotonation of the oxygen. o Favored at reasonably hot temperatures (140 C), because higher temperatures would favor elimination o Works best on primary and methyl alcohols. It is an SN2 after all! o If you try to make asymmetrical ethers this way, you will get a mixture of products. Because you get a mixture of products, you can call this a low-yield reaction. Pinacol Rearrangement a reaction of vicinal diols o First, the hydroxyl group is protonated (see a pattern here?) H+OOHHOHO+HHH+OOHHOHO+HH o Then water falls off. OHO+HHOH+ o A methyl shift happens because the resulting carbocation is resonance-stabilized. O+HOHOH++ The resonanc e form with the positive oxygen is the most stable because of the octet rule.

5 O Finish it off by deprotonating the oxygen! O+HO o This reaction occurs with other vicinal diols as well, so don t expect it to just be pinacol on the quiz or test. Mr. Baker always gives you symmetrical molecules for this reaction, so it doesn t matter which hydroxyl you protonate in the first step. If you were given an asymmetrical molecule then you would get a mixture of products. o To get to the product without thinking about the mechanism: OHOHH+OOHOHH+O Make one of the OH s into a carbonyl. Put two methyls where they other hydroxyl was. Periodic Acid Cleavage of Vicinal Diols o Just cleave the bond between the two carbons and turn the alcohols into carbonyls. HIO4 OHOHOHOHIO4 OHOHOHO o Do not further oxidize aldehydes to carboxylic acids. Fischer Esterification o This is a big one to know!

6 ACS, MCAT, DAT, PCAT, OAT, etc. will expect you to know this! o Overall: Carboxylic acid + alcohol ester + water o Step 1: protonation of carbonyl to activate it for attack. H+OOHOHO+HH+OOHOHO+H o Step 2: Alcohol attacks carbonyl carbon of the acid OHO+HOHOHOHO+H o Step 3: Deprotonation of the oxygen from the alcohol OHOHO+HOHOHO o Step 4: Protonation of one of the oxygens from the acid H+OHOHOOHO+HHOH+OHOHOOHO+HHO o Step 5: Loss of water, forming a resonance-stabilized carbocation O+HOOHO+HHOOHO+ o Step 6: Deprotonation of carbonyl O+HOOO Esters of inorganic acids o Just take an acid that isn t a carboxylic acid (phosphoric, sulfuric, etc) and add an alcohol to make a different type of ester. OHHNO3 ONO2glycerinenitroglycerineOHONO2 ONO2 OHOHHNO3 ONO2glycerinenitroglycerineOHONO2 ONO2OH o Know that DNA and RNA are polymers with a phosphate ester in there.

7 Williamson Ether Synthesis o Just an SN2 with an alkoxide as the nucleophile. o Remember that you want the substrate to be either methyl or primary. An alkoxide would abstract a proton from a 2 or 3 substrate, in an E2 mechanism o Ex. How would you synthesize the following ether from two alcohols? O o Answer: TsClTsOHOTsClTsOHO NaHOHO NaHOHO OTsO OOTsO O