Aldehydes, Ketones, Carboxylic Acids and Amides

The carbonyl group >C=O is one of the most biologically important chemical entities in Organic Chemistry

Aldehydes, Ketones, Carboxylic Acids and Amides

Four families of compounds contain the carbonyl group:

R

C

O

H Aldehydes

R

CR

O

Ketones

R C

OH

O

R C

HN R

O

Carboxylic Acids

Amides

R

C

O

H Aldehydes

•We replace the –e ending of compounds with –al for aldehydes

•We know that aldehyde has to be at the end of the molecule.

•Why?

H

C

O

H

H3C C

H

O

MethanolorFormaldehyde

EthanolorAcetaldehyde

Aldehydes are found in many oils and natural extrcts

R

CR

O

Ketones

We replace the –e ending with -one

H3C C

CH3

O

Propanone

The simplest Ketone.

Why?

R C

O -

R C

OH

OO

+ H+

Carboxylic Acid

•Weak Acids

•They have an acidic proton because of the electron withdrawing effect of the carbonyl oxygen and resonance stabilization of the resultant carboxylate anion

H

H

H

OH

O

O

Formaldehyde

Formic Acid

Carboxylic AcidsNamed by replacing the –e with –oic acid

OH

O

O

H

H3C

H3C OH

Benzoic Acid

Acetic AcidAcetaldehyde

From Alcohols to Acids

H3CCH2

OH

CH3

CH H3C C

OH

O O

Progressively Oxidizing (adding Oxygen) the alcohol allows us to go from an alcohol to a carboxylic acid

AmidesAn Amide is a compound containing an amine bound to a carboxyl group

R

CO

N R

H

An Amide

A peptide bond is an example of an amide

Note:

When drawing organic structures, keep in mind the hybridization of the carbons

• Alkanes have sp3 hybridized carbons– Geometry?

• Carbonyl carbons have sp2 hybridized carbons– Geometry?

Esters

• The fatty acids in our bodies are examples of esters

• Esters are formed from the condensation of a carboxylic acid and an alcohol

H2C

HC

H2C

OH

OH

OH

HO

O

HO

O

HO

O

Amines

NH H

H

NH H

CH3

NH CH3

CH3

NH3C CH3

CH3

Amine Methylamine

1° Amine

Dimethylamine

2° Amine

Trimethylamine

3° Amine

•Amines are compounds derived from ammonia

•Amines tend to be associated with strong, often unpleasant odors

Putrescine NH2(CH2)4NH2

Cadaverine NH2(CH2)5NH2

Amino Acids• The building blocks

of proteins are amino acids

• Amino Acids have an amino group and a carboxylic acid on them

• When the ribosome forms a protein from amino acids, it does so in a condensation reaction that forms an amide

Organic Chemistry 2: Important Reactions

In the biological world, organisms are capable of synthesizing or degrading nearly any molecule

For the remainder of this class, we are going to look at the chemistry of basic biological molecules and the reaction mechanisms these molecules are involved in

Reaction TypesWe are going to focus on 3 basic reaction types: 1. Nucleophilic Substitution Reactions: An electron rich atom

(nucleophile) attacks a electron deficient atom2. Acid-Base Catalysis: Certain amino acid side chains of

enzymes can accept or donate protons, making them act like acids (donate protons) or bases (accept protons)

3. Condensation Reactions: The involve the combining of two molecules to form a larger molecule and a smaller one

• The reverse reaction is called a Hydrolytic Reaction. We’ll look at those as well.

Nucleophilic Substitution Reactions

Terminology:• Nucleophile: An electron rich atom. May be

negatively charged or have an available lone pair• Electrophile: An electron poor atom. May or may

not have a positive charge

Nucleophilic Substitution Reactions

• Two types of Sn Reactions Exist• They are classified and named based upon the slowest (rate limiting)

step: Sn1 and Sn2• The General form of these reactions is:

R:X + :Z --> R:Z + X

:Z is the nucleophileX is the leaving group

• In a condensation reaction for the formation of a lipid from a glycerol and a fatty acid, a glycerol hydroxyl is the nucleophile attacking the carbonyl carbon of the carboxylic acid

• Remember: The nucleophile attacks atoms of partial positive charge

Types of Nucleophilic Substitution Reactions

• Sn1: The rate is dependent on the leaving group leaving– Stands for: Substitution Nucleophilic

Unimolecular

Note: The first step is the dissociation of the chlorine

Types of Nucleophilic Substitution Reactions

• Sn2: The rate is dependent on the nucleophile and the substrate forming a bond at the SAME TIME the leaving group dissociates– Stands for: Substitution Nucleophilic

Bimolecular•Steric hindrances may prevent Sn2 reactions

•The concentration of both reactants affects the rate

Nucleophilic Substitution Reactions

• Actually, many reactions are mixtures of Sn1 and Sn2 mechanisms

• Many factors affect whether a reaction proceeds via the Sn1 or Sn2 route, including:– Nucleophilicity– Bond polarizability– Leaving group stability– Solvent composition

• Think about these factors, you will see them again in Organic Chemistry

General Acid-Base Catalysis• In these reactions, groups accept or donate protons,

thereby acting as acids or bases

• In proteins, acid-base catalysis is mediated by side chains containing:– Imidazole, hydroxyl, carboxyl, sulfhydryl, amino and phenol

groups

• For an enzyme catalyzed reaction in which the enzyme abstracts a proton from a substrate, the protein is acting like a base

R-H+ + R-O- --> R + R-OH

General Acid-Base Catalysis• For an enzyme catalyzed reaction in which the enzyme donates

a proton to a substrate, the protein is acting like an acid

R-H+ + R-O- --> R + R-OHWe would call this General Acid Catalysis

• For an enzyme catalyzed reaction in which the enzyme abstracts a proton from a substrate, the protein is acting like a base

R-H+ + R-OH --> R + R-O-

We would call this General Base Catalysis

General Acid-Base Catalysis: An Example

• Keto-Enol Tautomerization

Adapted from Voet, Voet and Pratt. Fundamentals of Biochemistry, 3rd Ed. 2008.

General acid catalysis: Partial proton transfer from an acid lowers the free energy of the high-free energy carbanionlike transition state of the keto-enol tautomerization

General base catalysis: The rate can be increased by partial proton abstraction by a base.

Uncatalyzed

Concerted acid-base catalyzed reactions involve both processes occurring simultaneously.

General Acid-Base Catalysis: An Example

Enzymatic Degradation of 4-Nitrophenylacetate proceeds via a General Acid-Base mechanism

•Imidazole nitrogen extracts proton from water initiating the reaction

Condensation Reactions

• Two molecules combine with the generation of a smaller molecule

Condensation Reactions

• Reaction of Acetic Acid and Ethanol

Looking at the Reaction Mechanism

1. The carbonyl carbon is:• Electron deficient• In a trigonal planar geometry

• 120º between substituents

2. The carbonyl oxygen is pulling electrons towards it

• Resonance stabilization3. The Lone Pair of the alcohol oxygen can react

with the carbonyl carbon to set the whole thing in motion

4. Remember your VSEPR Geometry

Condensation Reactions: Making Lipids from Sugars and Fatty Acids

• Your cells can synthesize lipids from glycerol and fatty acids in a condensation reaction

Condensation Reactions: Polymerizing Carbohydrate Monomers

Condensation Reactions: Forming a Peptide Bond

1. What are the amino acids in the figure?

2. What function group is formed?

Its not really this simple, but it illustrates a point!

Hydrolysis: The Opposite of Condensation

•In a hydrolytic reaction, we add the elements of water (H+ and OH-) across a bond

•Many enzymes use this kind of reaction to degrade polymers

•Lipases: Hydrolyze lipid esters

•Glycosidases: Hydrolyze carbohydrate polymers

•Peptidases: Hydrolyze peptide bonds

•Compound Name + ase : Usually indicates a hydrolase (but not always!)

•If it isn’t a compound name and ase, then it usually does something else:

•Lyase

•Reductase

•Kinase

•Transferase

Hydrolysis of Sugar Polymers

• We add water across the Glycosidic Bond of Maltose to break it and generate 2 monomers

• Catalyzed by a glycosidase (Maltase perhaps?)

Hydrolysis of Peptides

• Dipeptide (What are the amino acids) is hydrolyzed to ???

• Catalyzed by a peptidase or a protease