of carbonyl group chemistry An overview of carbonyl group chemistry

CARBONYL GROUP sp2      sp2 sp2      sp2 C=O bond length 1.22 A C=C bond length 1.33 A

CARBONYL GROUP ELECTRONIC STRUCTURE Lone-pair electrons - Lone-pair electrons π-bond + Carbon or Hydrogen Carbon or Hydrogen

CARBONYL GROUP ORBITALS

POLARIZATION OF CARBONYL GROUP AND ITS REACTIVITY Nucleophilic oxygen reacts with acids and electrophiles - + Electrophilic carbon reacts with bases and nucleophiles

TYPES OF CARBONYL COMPOUNDS ALDEHYDES Hydrogen or carbon cannot stabilize negative charge and therefore cannot act as leaving group KETONES

TYPES OF CARBONYL COMPOUNDS Carboxylic acid Carboxylic acid chloride Carboxylic acid anhydride Carboxylic acid ester Carboxylic acid amide Electronegative atom (oxygen, halogen, nitrogen) bonded to acyl group R-CO- can stabilize a negative charge, therefore groups –OH, -Cl, -OCOR’, -OR’, -NH2 can serve as leaving groups in substitution reactions.

TYPES OF CARBONYL COMPOUNDS Cyclic acid anhydride Cyclic ester (lactone) Cyclic amide (lactam)

POLARITY OF CARBONYL COMPOUNDS Type of carbonyl group Dipole moment (D) HCHO CH3CHO (CH3)2CO PhCOCH3 Cyclobutanone CH3COOH CH3COCl CH3COOCH3 CH3CONH2 CH3CON(CH3)2 Aldehyde Ketone Carboxylic acid Acid chloride Ester Amide 2.33 2.72 2.88 3.02 2.99 1.74 1.72 3.76 3.81

TYPES OF CARBONYL COMPOUNDS REACTIONS GENERAL MECHANISMS Nucleophilic addition Nucleophilic acyl substitution -Substitution Condensation reactions

Nucleophilic addition to carbonyl group 1st step Carbonyl carbon rehybridizes from sp2 to sp3

Nucleophilic addition to carbonyl group 2nd step Two ways of stabilization of tetrahedral intermediate

Nucleophilic addition to carbonyl group EXAMPLE 1 – addition of methylmagnesium bromide to cyclohexanone Synthesis of tertiary alcohol from ketone

Nucleophilic addition to carbonyl group EXAMPLE 2 – cyclohexanone imine formation Net effect – replacing C=O by C=NR

Nucleophilic acyl substitution Net effect – replacing of group Y with nuclephile. -Y is called leaving group Y = -OR (ester) -OCOR (anhydride) -Cl (acid chloride) -NH2, -NHR, -NR2 (amide)

Nucleophilic acyl substitution EXAMPLE – ester synthesis from acid chloride and alkoxide Net effect – replacing of Cl by OR

-Substitution reactions -substituted carbonyl compound Intermediates

-Substitution reactions Net effect – extending of carbonyl compound hydrocarbon framework by –CH2R fragment at -carbon

-Substitution reactions EXAMPLE – -methylation of cyclohexanone

Carbonyl condensation reactions New C-C bond Two aldehydes Aldol product (aldehyde + alcohol)

Carbonyl condensation reactions Carbonyl condensation reaction is a combination of -substitution step and nucleophilic addition step acetaldehyde By condensation of acetaldehyde 3-hydroxybutanal is prepared 3-hydroxybutanal

Nucleophilic addition reactions of carbonyl compounds Alcohol Alcohol Cyanohydrin Alkene Imine Alkane Acetal Enamine

Negatively charged nucleophiles Neutral nucleophiles Hydroxide ion Hydride ion A carbanion An alkoxide ion Cyanide ion Water An alcohol Ammonia An amine