Transcript Orbitals - drjosephryan.com

14.2 Preparing Aldehydes and Ketones
Aldehydes from oxidation of primary alcohols using the DessMartin periodinane reagent
Preparing Aldehydes and Ketones
Aldehydes from reduction of carboxylic esters using
diisobutylaluminum hydride (DIBAH)
Preparing Aldehydes and Ketones
Secondary alcohols are oxidized by variety of chromium-based
reagents to give ketones
Aryl ketones from Friedel-Crafts acylation reactions
Nucleophilic Addition of Grignard and Hydride
Reagents: Alcohol Formation
Mechanism of Grignard
Reaction
Nucleophilic Addition of Grignard and Hydride
Reagents: Alcohol Formation
In an analogous manner the reaction of aldehydes and
ketones with hydride reagents may be represented as
proceeding through a nucleophilic addition of a hydride ion
(:H–) to the C=O carbon
• LiAlH4 and NaBH4 act as if they are donors of hydride ion
14.7 Nucleophilic Addition of Amines: Imine
and Enamine Formation
Primary amines, RNH2, add to aldehydes and ketones to yield
imines, R2C=NR
Secondary amines, R2NH, add similarly to yield enamines,
R2N-CR=CR2
Nucleophilic Addition of Amines: Imine and
Enamine Formation
Imines are common biological intermediates where they are
often called Schiff bases
Nucleophilic Addition of Amines: Imine and
Enamine Formation
Imine and enamine formations reach maximum rate
around pH = 4 to 5
• Slow at pH > 5 because there is insufficient H+ present in
solution to protonate intermediate carbinolamine –OH to
yield the better leaving group –OH2+
• Slow at pH < 4 because the basic amine nucleophile is
protonated and initial nucleophilic addition cannot occur
Worked Example 14.1
Predicting the Product of Reaction between a
Ketone and an Amine
Nucleophilic Addition of Alcohols: Acetal
Formation
Acetal and hemiacetal groups are common in carbohydrate
chemistry
• Glucose, a polyhydroxy aldehyde, undergoes intramolecular
nucleophilic addition
• Exists primarily as a cyclic hemiacetal
14.9 Nucleophilic Addition of Phosphorus Ylides:
The Wittig Reaction
Wittig reaction
• Converts aldehydes and ketones into alkenes
• Phosphorus ylide, R2C–P(C6H5)3, adds to aldehyde or
+
ketone to yield dipolar, alkoxide ion intermediate
•
Ylide (pronounced ill-id) is a neutral, dipolar compound with
adjacent positive and negative charges
• Also called a phosphorane and written in the resonance form
R2C=P(C6H5)3
• Dipolar intermediate spontaneously decomposes through a
four-membered ring to yield alkene and triphenylphosphine
oxide, (Ph)3P=O
• Wittig reaction results in replacement of carbonyl oxygen
with R2C= group of original phosphorane
Nucleophilic Addition of Phosphorus Ylides:
The Wittig Reaction
Wittig reaction mechanism
Nucleophilic Addition of Phosphorus Ylides:
The Wittig Reaction
• Phosphorus ylides are prepared by SN2 reaction of
primary and some secondary alkyl halides with
triphenylphosphine, (Ph)3P, followed by treatment with
base
Nucleophilic Addition of Phosphorus Ylides:
The Wittig Reaction
Wittig reactions used commercially to synthesize numerous
pharmaceuticals
Worked Example 14.3
Synthesizing an Alkene Using a Wittig Reaction
What carbonyl compound and what phosphorus ylide
might you use to prepare 3-ethylpent-2-ene?
Worked Example 14.3
Synthesizing an Alkene Using a Wittig Reaction
Solution
Biological Reductions
Cannizzaro reaction is a nucleophilic acyl substitution reaction
of aldehydes and ketones
•
•
•
OH¯ adds to aldehyde to give tetrahedral intermediate
H:¯ ion is transferred to a second aldehyde
The aldehyde accepting the H:¯ ion is reduced and the aldehyde
transferring the H:¯ is oxidized
Biological Reductions
Cannizzaro reaction mechanism is analogous to biological reduction
in living organisms by nicotinamide adenine dinucleotide, NADH
•
NADH donates H:¯ to aldehydes and ketones, similar to tetrahedral
alkoxide intermediate in Cannizzaro reaction
Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones
Conjugate addition occurs because the nucleophile can add to
either one of two electrophilic carbons of the a,b-unsaturated
aldehyde or ketone
Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones
Conjugated double bond of a,b-unsaturated carbonyl is
activated by carbonyl group of the aldehyde or ketone
• C=C double bond is not activated for addition in absence of
carbonyl group
Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones
Primary and secondary amines add to a,b-unsaturated
aldehydes and ketones to yield b-amino aldehydes and
ketones
•
Both 1,2- and 1,4-addition occur
• Additions are reversible
• More stable conjugate addition product accumulates
Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones
Conjugate addition of an alkyl or other organic group to an a,bunsaturated ketone (but not aldehyde) is a useful 1,4addition reaction
Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones
Conjugate addition of alkyl groups to an a,b-unsaturated
ketone (not aldehyde) is accomplished with a lithium
diorganocopper reagent, R2CuLi (Gilman reagent)
•
Lithium diorganocopper reagent is prepared by reaction of 1
equivalent of copper(I) iodide and 2 equivalents of an
organolithium reagent, RLi
• Organolithium reagent is prepared by reaction of lithium metal with
an organohalide
Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones
Primary, secondary, and even tertiary alkyl groups undergo
conjugate addition
•
Alkynyl groups react poorly
• Grignard reagents and organolithium reagents normally give direct
carbonyl addition to a,b-unsaturated ketones
Worked Example 14.4
Using a Conjugate Addition Reaction
How might you use a conjugate addition reaction to
prepare 2-methyl-3-propylcyclopentanone?
Worked Example 14.4
Using a Conjugate Addition Reaction
Solution
Spectroscopy of Aldehydes and Ketones
Spectroscopy of Aldehydes and Ketones
Aldehyde protons (RCHO) absorb near 10 d in the 1H NMR
• Aldehyde proton shows spin-spin coupling with protons on
the neighboring carbon, with coupling constant J ≈ 3 Hz
• Hydrogens on carbon next to a carbonyl group are slightly
deshielded and absorb near to 2.0 to 2.3 d
Spectroscopy of Aldehydes and Ketones
Carbonyl-group carbon atoms of aldehydes and ketones have
characteristic 13C NMR resonances in the range of 190 to
215 d