Reactions of aldehydes and ketones: oxidation reduction nucleophilic addition Aldehydes are easily oxidized, ketones are not. Aldehydes are more reactive in nucleophilic additions than ketones.

alkane alcohol reduction reduction aldehyde ketone addition product nucleophilic addition oxidation carboxylic acid

nucleophilic addition to carbonyl:

Mechanism: nucleophilic addition to carbonyl 1) 2)

Mechanism: nucleophilic addition to carbonyl, acid catalyzed 1) 2) 3)

Aldehydes & ketones, reactions: Oxidation Reduction Addition of cyanide Addition of derivatives of ammonia Addition of alcohols Cannizzaro reaction Addition of Grignard reagents 8) (Alpha-halogenation of ketones) 9) (Addition of carbanions)

1) Oxidation Aldehydes (very easily oxidized!) CH3CH2CH2CH=O + KMnO4, etc.  CH3CH2CH2COOH carboxylic acid CH3CH2CH2CH=O + Ag+  CH3CH2CH2COO- + Ag Tollen’s test for easily oxidized compounds like aldehydes. (AgNO3, NH4OH(aq)) Silver mirror

Ketones only oxidize under vigorous conditions via the enol.

b) Methyl ketones: Yellow ppt test for methyl ketones

2) Reduction: To alcohols

Then + H+  alcohol

Reduction b) To hydrocarbons

3) Addition of cyanide

1) 2)

Cyanohydrins have two functional groups plus one additional carbon Cyanohydrins have two functional groups plus one additional carbon. Nitriles can be hydrolyzed to carboxylic acids in acid or base:

4) Addition of derivatives of ammonia

1) 2) 3)

melting points of derivatives ketones bp semi- 2,4-dinitro- oxime carbazone phenylhydrazone 2-nonanone 195 119 56 acetophenone 202 199 240 60 menthone 209 189 146 59 2-methylacetophenone 214 205 159 61 1-phenyl-2-propanone 216 200 156 70 propiophenone 220 174 191 54 3-methylacetophenone 220 198 207 55 isobutyrophenone 222 181 163 94

5) Addition of alcohols

Cannizzaro reaction. (self oxidation/reduction) a reaction of aldehydes without α-hydrogens

Formaldehyde is the most easily oxidized aldehyde Formaldehyde is the most easily oxidized aldehyde. When mixed with another aldehyde that doesn’t have any alpha-hydrogens and conc. NaOH, all of the formaldehyde is oxidized and all of the other aldehyde is reduced. Crossed Cannizzaro:

7) Addition of Grignard reagents.

1) 2)

#3 synthesis of alcohols #3 synthesis of alcohols. Used to build larger molecules from smaller organic compounds.

Aldehydes & ketones, reactions: Oxidation Reduction Addition of cyanide Addition of derivatives of ammonia Addition of alcohols Cannizzaro reaction Addition of Grignard reagents 8) (Alpha-halogenation of ketones) 9) (Addition of carbanions)

Planning a Grignard synthesis of an alcohol: The alcohol carbon comes from the carbonyl compound. The new carbon-carbon bond is to the alcohol carbon. New carbon-carbon bond

“The Grignard Song” (sung to the tune of “America the Beautiful”) Harry Wasserman The carbonyl is polarized, the carbon end is plus. A nucleophile will thus attack the carbon nucleus. The Grignard yields an alcohol of types there are but three. It makes a bond that corresponds from “C” to shining “C.”

or

HX Mg ROH RX RMgX larger alcohol H2O ox. R´OH -C=O

Stockroom: alcohols of four-carbons or less: (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-2-propanol, 2-methyl-1-propanol.) benzene cyclohexanol any needed inorganic reagents or solvents.

Grignard synthesis of 4-methyl-2-pentanol from alcohols of four-carbons or less: Step one: determine the carbonyl compound and Grignard reagent that you would use: H2O CH3 CH3CHCH2MgBr + CH3CH=O CH3 CH3CHCH2CHCH3 OH Step two: show the syntheses of the Grignard reagent and the carbonyl compound from alcohols…

CH3 HBr CH3 Mg CH3 4-methyl-2-pentanol CH3CHCH2OH CH3CHCH2Br CH3CHCH2MgBr H+ K2Cr2O7 CH3 CH3CH2OH CH3CH=O CH3CHCH2CHCH3 special cond. OH 4-methyl-2-pentanol

2-phenyl-2-propanol

1-methylcyclohexanol

cyclohexylmethanol

ketone aldehyde RCOOH ROH ROR alkene RX Alcohols are central to organic syntheses RH alkyne

HX Mg ROH RX RMgX larger alcohol H2O ox. R´OH -C=O

Using the Grignard synthesis of alcohols we can make any alcohol that we need from a few simple alcohols. From those alcohols we can synthesize alkanes, alkenes, alkynes, alkyl halides, ethers, aldehydes, ketones, carboxylic acids… eg. Outline all steps in a possible laboratory synthesis of 3-methyl-1-butene from alcohols of four carbons or less. CH3 CH3CHCH=CH2

Retrosynthesis: alkenes, syntheses: 1. Dehydrohalogenation of an alkyl halide 2. Dehydration of an alcohol 3. Dehalogenation of a vicinal dihalide 4. Reduction of an alkyne Methods 3 & 4 start with compounds that are in turn made from alkenes.

Dehydration of an alcohol? CH3 H+ CH3CHCHCH3 yields a mixture of alkenes OH CH3 H+ CH3CHCH2CH2-OH yields a mixture of alkenes E1 mechanism via carbocation!

Dehydrohalogenation of an alkyl halide? CH3 KOH(alc) CH3CHCHCH3 yields a mixture of alkenes Br CH3 KOH(alc) CH3 CH3CHCH2CH2-Br CH3CHCH=CH2 only product  E2 mechanism, no carbocation, no rearrangement

CH3 HBr CH3 CH3CHCH2CH2-OH CH3CHCH2CH2-Br 1o alcohol, SN2 mechanism, no rearrangement! CH3 KOH(alc) CH3 CH3CHCH2CH2-Br CH3CHCH=CH2 Use the Grignard synthesis to synthesize the intermediate alcohol from the starting materials.

CH3 PBr3 CH3 Mg CH3 CH3CHCH2-OH CH3CHCH2Br CH3CHCH2MgBr K2Cr2O7 CH3OH H2C=O special cond. H2O CH3 CH3CHCH2CH2-OH HBr CH3 KOH(alco) CH3 CH3CHCH=CH2 CH3CHCH2CH2-Br

Notes on Exam I: Given the structures, be able to name aldehydes/ketones using either common or IUPAC names. Be able to outline all steps in the mechanisms: nucleophilic addition & acid catalyzed nucleophilic addition. Be able to draw structures for the organic products of the reactions of aldehydes/ketones. Be able to outline possible laboratory syntheses of aldehydes/ketones and Grignard syntheses of alcohols, etc. Be able to match structures with their IR spectra. Be able to predict the 1H-nmr spectrum, given the structure. Given the 1H-nmr spectrum and formula, be able to draw the structure of the compound.