MCAT Study Guide Ochem Ch. 6 – Aldehydes and Ketones 2017-08-15T06:45:06+00:00

I.          6.1:  ALDEHYDES AND KETONES

AQUEOUS OXIDANTS ANHYROUS OXIDANTS
Chromic acid (H2CrO4) Pyridinium Chlorochromate (PCC)
Chromate salts (CrO42-)
Dichromate salts (Cr2O72-)
Permanganate (MnO4)
Chromium Trioxide (CrO3)

 A.     ACIDITY AND ENOLIZATION

1.     α-protons are relatively acidic, so can be removed with a strong base (OH) or alkoxide ion (OR) to yield a resonance stabilized carbon

2.     The remaining electron pair that is left behind can be delocalized in the carbonyl π system

3.     Enolate ion – resonance stabilized carbanion where an α-proton is removed

a)     This is negatively charged an nucleophilic (at the carbon where the proton was extracted)

B.     KETO-ENOL TAUTOMERISM

1.     Tautomerism – two molecules that are readily interconvertible constitutional isomers in equilibrium

2.     Ketone is more stable, therefore equilibrium lies closer to the left

C.    NUCLEOPHILIC ADDITION REACTIONS TO ALDEHYDES AND KETONES

1.     Because oxygen is has high electronegativity, the C of the carbonyl group is slightly positively charged and therefore electrophilic

a)     It will attract nucleophiles and can be reduced (OIL RIG)

2.     Nucleophilic addition reactions are defined by bond changes:

a)     π bond broken, 2 σ bonds formed

b)     This allows carbonyl group to convert into alcohols via hydride reduction

3.     NOTE:  LiAlH4 and NaBH4 are common reducing agents!! They add hydride (H and pair of electrons) to carbonyl

D.    ORGANOMETALLIC REAGENTS (reducing agents)

Basic structure is RM+

1.     Act as electron rich (anionic) carbon atoms that function as strong bases or nucleophiles

2.     Most common are Grignard and lithium reagents

a)     Grignard reagent – R–MgBr

b)     Organolithium reagent – R–Li

3.     Both require ether and H3O

E.     WITTIG REACTION

Don’t know mechanism, just recognize

1.     Wittig reagents – phosphonium ylides (Ph3P–R)

F.     ACETALS AND HEMACETALS

1.     Structure

a)     Acetal must have the structure R2C(OR’)2

b)     Hemiacetals only have 1 -O–R group attached to the carbon

2.     Acetyl formation – formed when aldehydes or ketones react with alcohols in the presence of acid

G.    IMINE FORMATION

Closely resembles acetyl formation

1.     Catalyzed by a weakly acidic buffer system

2.     The H’s attached to the N are lost, with the O, in the form of water

H.    ALDOL CONDENSATION

Happens when the enolate anion of a carbonyl compound reacts with the carbonyl group of another carbonyl compound

1.     3 important points:

a)     Requires a strong base (OH or RO) to first remove the α proton

b)     One of the aldehyde/ketones must act as a source for the enolate ions, while the other will come under nucleophilic attack by the enolate carbanion

c)     The condensation does not require the two carbonyl groups to be the same

(1)   Cross aldol condensation – the condensation of two different carbonyl groups

(2)   To avoid a mixture of products, choose one group with no α protons to remove so it cannot be converted into the enolate anion and therefore cannot be the nucleophile

2.     The α carbon of the enolate ion attaches to the carbonyl carbon of the other compound

a)     These new compounds are called β–hydroxy carbonyl compounds

3.     Heating of β–hydroxy carbonyl compounds – this will result in an elimination reaction (dehydration) to form α,β-unsaturated carbonyl compound

I.    CONJUGATE ADDITION TO α,β-UNSATURATED CARBONYL COMPOUNDS

1.     With α,β-unsaturated carbonyl compounds the nucleophile attacks the β-carbon, thereby unsaturating the alkene and attaching to that spot

II.          6.2:  CARBOXYLIC ACIDS

Important in biochem! Fatty acids are long chains of carboxylic acids

A.     ACIDITY AND HYDROGEN BONDING

1.     Carboxylic acids are stable because of resonance

B.     INDUCTIVE STABILIZATION OF CARBOXYLATE IONS BY ELECTRON-WITHDRAWING GROUPS

1.     Inductive effect – Electron withdrawing groups further stabilize carboxylic acids by increasing the stability of the negative charge of the carboxylic acid ion

2.     The closer the electron-withdrawing group, the stronger the inductive effect

3.     Electron-withdrawing groups make the acid more acidic!!

C.    HYDROGEN BONDING IN CARBOXYLIC ACIDS

1.     Carboxylic acids form strong H-bonds because they contain a H-donor and H-acceptor

D.    DECARBOXYLATION REACTIONS OF β-KETO ACIDS

1.     Carboxylic acids that have carbonyl groups β to the carboxylate are unstable

2.     They lose a CO2 from the β-keto acid

 

III.          6.3:  CARBOXYLIC ACID DERIVATIVES

A.     NUCLEOPHILIC ADDITION ELIMINATION REACTION

1.     This is when a nucleophile ends up replacing an electronegative group on a carboxylic acid derivative

B.     ESTERIFICATION REACTIONS

1.     Occurs when a carboxylic acid reacts with an alcohol in the presence of a catalytic amount of acid

2.     The H of the acid is replaced with the R group of the alcohol, resulting in an ester

C.    ACIDIC AND BASIC HYDROLYSIS OF ESTERS

1.     Esters can react with either an acid or a base (nucleophile or electrophile), and by differing mechanisms, end up as a carboxylic acid

2.     In any nucleophilic addition-elimination reaction of an acid derivative, there will always be a tetrahedral intermediate → is this important?

D.    SAPONIFICATION:  AND EXAMPLE OF BASE-MEDIATED HYDROLYSIS REACTION

1.     The treatment of triaclyglycerides with strong base yields a molecule of glycerol and 3 fatty acids

E.     SYNTHESIS OF THE CARBOXYLIC ACID DERIVATIVES

1.     Acid Halides (2 ways)

a)     Carboxylic acids + SOCl2 or PX3 makes alkyl halide

2.     Acid Anhydrides (2 ways)

a)     Made by the condensation of 2 carboxylic acids with the loss of water

b)     Carboxylic acid plus acid halide

3.     Esters (2 ways)

a)     Esterification, see above (carboxylic acid + alcohol)

b)     Acid halide or anhydride + corresponding alcohol

4.     Amides

a)     Amine + corresponding acid halide, anhydride, or ester

b)     Cannot be made from carboxylic acid directly!

5.     Carboxylic Acids

a)     Can be made from any derivative by heating in acidic aqueous solution

6.     Relative Reactivity of Carboxylic Acid Derivatives

a)     Directly related to the basicity of the leaving group (stronger the base, the worse the leaving group, and therefore the less reactive)

 

 IV.          6.4:  CYCLOADDITION REACTIONS

A.     Concerted reactions

Reactions that occur in one step without the formation of intermediates; usually highly stereoselective

B.     Dies-Alder reaction

Concerted reaction where a cyclohexene ring is formed from the cycloaddition of a diene with a dieneophile

 

 

SUMMARY

 

 

CHAPTER 6 SUMMARY:

○       The C=O bond is very polarized due to the high electronegativity of O, resulting in the carbon of the carbonyl group being very electrophilic

○       Protons α to the carbonyl are acidic and can be removed by a strong base to yield a nucleophilic carbanion, or enolate

○       Keto-enol tautomerism is the rapid equilibration of the more stable keto form of a carbonyl and the less stable enol form where the α-proton shifts to the carbonyl oxygen

○       Nucleophilic additions involve the attack of a nucleophile on the carbon of an aldehyde or ketone; these reactions break one of the π bond to form two σ bonds

○       Hydride reduction, a type of nucleophilic addition, can convert ketones or aldehydes into alcohols; alcohols can be converted back to carbonyl compounds using oxidizing agents

○       An aldol condensation is a C-C bond forming reaction where the carbonyl carbon of one molecule is the electrophile, while the α carbon of another carbonyl is the nucleophile

○       α β -Unsatruated carbonyl compounds are electrophilic at the β carbon and undergo Michael, or conjugate, addition reactions

○       Acidity of carboxylic acid result from the resonance stability of the carboxylate anion

○       Electron withdrawing groups increase the acidity of carboxylic acids by stabilizing the negative charge of the carboxylate anion via the inductive effect

○       The reactivity of carboxylic acid derivatives decreases as follows:

■       acid halide > acid anhydride > ester > amide

○       Nucleophilic addition to the carbonyl carbon in a carboxylic acid derivative is usually followed by elimination due to the presence of a good electronegative leaving group

MCAT Study Guide Ochem - Kim Matsumoto


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