Organic Chemistry Unit 3

Formaldehyde

Common aldehyde

Acetone

Acetone

Common Ketone

Nomenclature of Aldehydes

When naming the parent, the suffix “-al” indicates the presence of an aldehyde group (In an alkane the ending “e” changes)

When numbering the parent chain of an aldehyde, the aldehydic carbon is assigned number 1, despite the presence of alkyl substituents, π bonds, or hydroxyl groups (indicate chirality with R/Z)

A cyclic compound containing an aldehyde group immediately adjacent to the ring is named as a carbaldehyde

Benzaldehyde

Nomenclature of Ketones

When naming the parent, the suffix “-one” indicates the presence of a ketone group (in an alkane, the “e” changes to “one”

The carbon number connected to the ketone can be placed before suffix or before the parent

Acetophenone

Benzophenone

Ethyl Propyl ketone

what is of higher significance in naming, ketone or aldehyde

Aldehyde

Oxidation of Primary Alcohols (into aldehhyde)

Ozonolysis of Alkenes(into aldehyde)

Hydroboration- Oxidation of Terminal Alkynes

Oxidation of Secondary Alcohols (into ketone)

Ozonolysis of Alkenes (into ketone)

Acid- Catalyzed Hydration of Terminal Alkynes

Friedel-Ceafts Acylation (into ketone)

Reactivity of Ketones vs aldehydes

Aldehydes are generally more reactive than ketones toward nucleophilic attack

A ketones two alkyl groups contributes to more steric interacts during the attack compared to an aldehydes one alkyl group (steric effects)

Since alkyl groups are electron donating, a ketone having two electron donating alkyl groups (one more than an aldehyde) stabilize the partial positive charge of electrophilic carbon, making it less reactive.

Nucleophilic addition in basic conditions (product/mechanism)

Nucleophilic addition in acidic conditions (product/mechanism)

Possible Nucleophiles

Hydrate

Hydrate formation (ketone)

Position of Equlibrum during hydrate formation

The position of equilibrium generally favors the carbonyl group rather than the hydrate, except in the case of very simple aldehydes, such as formaldehyde

Base catalyzed Hydration (formaldehyde)

Acid Catalyzed hydration(formaldehyde)

Acetal

Common acid catalysts

TsOH and H2SO4

Acetal Formation Reagents

Aldehyde/Ketone

ROH

Acid Catalyst

Acetal Formation mechanism

Notes: The identity of the acid, HA+, is most likely a protonated alcohol, which received its extra proton from the acid catalyst.

The oxonium ion is deprotonated by a weak base (A), which is likely to be a molecule of alcohol present in solution.

Acid is not consumed in the process

Cyclic Acetal formation

Acetals as a protecting group

Can protect ketones from reacting (i.e. in reactions involving carboxylic acid)

Reagents for forming protecting group

Reagents for removing a protecting group

Protecting group example problem

Hemiacetal

Very difficult to isolate and is usually an intermediate

Stable hemiacetal formation

Imine

Forms when a primary amine reacts with an aldehyde/ketone

aldehyde to imine

Ketone/Aldehyde

CH3NH2

-H20

Acid catalyzed

Imine Formation Mechanism

In imine formation, why doesn’t the ketone get protinated

in the presence of an amine, any strong acid catalyst will transfer its proton to the amine, giving an ammonium ion

This process is effectively irreversible due to the vast pKa difference. The acidic species in solution will be ammonium ions rather than HCl, and under these conditions protonation of the ketone is highly unlikely, since protonated ketones are extremely acidic (pKa ≈ −7).

Relates to why ideal pH for imine formation is 4-5

Enamine

Forms when an aldehyde/ketone reacts with a secondary amine in acidic conditions

Enamine Formation Reagnets

Aldehydes/Ketones

R2NH

-H2O

Enamine Formation

Identical to mechanism for imine formation except for the last step

Hydrazone

Wolff-Kishner Reduction (starting with ketone)

Reducing a ketone to an alkane

Wolff-Kishner Reduction Mechanism(don’t need to know?)

N2 gas step is irreversable and allows favorable yields.

Hydrolysis of Acetals

Do not undergo hydrolysis under aqueous basic conditions

Reagent is H3O+

Hydrolysis of Acetals Mechanism

Imine Hydrolysis

Enamine Hydrolysis

Thioacetal

thioacetal reagents

2 RSH

Acid Catalyst

Cyclic thioacetal Reagent/formation

Ketone/Aldehyde

HS-CH2-CH2-SH

Acid Catalyst

Desulfurization

Removing Sulfur molecules

Can be used in non-cyclic thioacetals too

Thioacetal

Raney Ni

Full reduction of ketone using a thioacetal

Hydride

H-

Common Hydride reducing agents

LiAlH4 (+ H30+ in second step)

NaBH4(, MeOH)

LiALH4 vs NaBH4

LiAlH4 is much stronger and will fully reduce a ketone

Mechanism of ketones/aldehydes reduction with hydride agents

What happens if chiral center formed(hydride reduction)

Racemic mixture forms

Grignard Reagent

R-CH2-MgBr

(with H3O+)

Produces a nucleophilic(negative charge) carbon

Grignard reaction with Ketone/aldehyde

When treated with a Grignard reagent, aldehydes and ketones are converted into alcohols, accompanied by the formation of a new C-C bond

What happens if racemic micture is formed in Grignard Reaction

Racemic mixture formed

Cyanohydrin

Cyanohydrin Reagents

HCN, KCN(produces more CN- anions)

Cyanohydrin formation mechanism

Wittig Reagent

Wittig Reaction

Very useful for forming mono/di/tri substituted alkenes

Wittig Reaction mechanism

Wittig reagent formation

Start: Alkyl halide

1)PPh3 2) n-BuLi(any very strong base)

Sn2

Stereoselectivity of Wittig reaction

For a Wittig reagent only containing a simple alkyl halide: (Z)-alkene is favored

For a Wittig reagent containing an electron-withdrawing group: (E)-alkene is favored

Why in electron withdrawing group containing Wittig reagents does the (E)-alkene predominate?

Better stabalize the carbanion by resonance and is the stabilized, lower energy Wittig reagent

(E)-alkene is generally more stable, lower in energy

Baeyer– Villiger Oxidation of Aldehydes and Ketones

Converts ketones/aldehydes into esters

mCPBA

Regioselectivity of ester formation in unsymmetrical ketone

Certain groups will migrate better than others, and the ester oxygen will be inserted accordingly

Will be inserted on the side on the following priority; H > 3° > 2°, Ph > 1° > methyl

Cyanohydrin to amine

Cyanohydrin to carboxylic acid