Acidity of -Hydrogens

Hydrogens alpha to a carbonyl group are more acidic than hydrogens of alkanes, alkenes, and alkynes but less acidic than the hydroxyl hydrogen of alcohols
Type of Bond pK a CH 3 CH 2 O-H O CH 3 CCH 2 -H CH 3 C C-H CH 2 = CH- H CH 3 CH 2 -H 16 20 25 44 51

Acidity of -Hydrogens
-Hydrogens are more acidic because the enolate anion is stabilized by
1. delocalization of its negative charge 2. the electron-withdrawing inductive effect of the adjacent electronegative oxygen
O CH3 - C-CH2 -H + :A-

O CH3 - C CH2

O-

:
CH3 - C= CH2 + H- A Enolate an ion

Keto-Enol Tautomerism
protonation of the enolate anion on oxygen gives the enol form; protonation on carbon gives the keto form
O CH3 - C-CH2 H- A OCH3 - C= CH2 H- A

Enolate an ion O A + CH3 - C-CH3 Keto form OH +A CH3 - C= CH2 Enol form

Keto-Enol Tautomerism
Keto-enol equilibria for simple aldehydes and ketones lie far toward the keto form
Keto form
O CH3 CH O CH3 CCH3 O

Enol form
OH CH2 = CH OH CH3 C= CH2 OH

% Enol at Equilibrium

6 x 10-5 6 x 10-7 1 x 10-6

OH

4 x 10-5

Keto-Enol Tautomerism
For certain types of molecules, however, the enol is the major form present at equilibrium
for -diketones, the enol is stabilized by conjugation of the pi system of the carboncarbon double bond and the carbonyl group
O O
conjugated system H H H O H HO H

O OH 1,3-Cycloh exanedione

Otro ejemplo de Tautomera

En este par de tautmeros, la fenol-imina se convierte fotoqumicamente, o sea, por absorcin de luz , en ceto-enamina. La irradiacin de la fenol-imina causa que el hidrgeno unido al oxgeno vaya al nitrgeno de la ceto-enamina. En la oscuridad la ceto-enamina, cambia a la fenol-imina ms estable

Oxidation of Aldehydes
Aldehydes are oxidized to carboxylic acids by a variety of oxidizing agents, including H2CrO4
CHO Hexanal H2 Cr O4 COOH Hexanoic acid

Ejemplos Oxidacin de Aldehidos

Facilmente se oxidan a cidos carboxlicos

Chapter 18

Oxidation of Aldehydes
Aldehydes are oxidized by O2 in a radical chain reaction
liquid aldehydes are so sensitive to air that they must be stored under N2
O 2 CH Benzaldehyde + O2 2 O COH Benzoic acid

Oxidation of Aldehydes
Aldehydes are also oxidized by Ag(I)
in one method, a solution of the aldehyde in aqueous ethanol or THF is shaken with a slurry of silver oxide
O CH3 O HO CH T HF, H 2 O N aOH HCl H2 O CH3 O HO O COH

+ A g2 O Vanillin

+ Ag Vanillic acid

Test Tollens
Adicionar solucin de amonaco a solucin de AgNO3 hasta que el precipitado se disuelva. Reaccin con aldehido forma un espejo de plata.
O R C H + 2
+ Ag(NH3)2

_ + 3 OH

O H2O 2 Ag + R C O

_ + 4

+ g(NH3)2

_ + 3 OH

O H2O 2 Ag + R C O

_ + 4 NH3 + 2 H2O

Oxidation of Ketones
ketones are not normally oxidized by chromic acid they are oxidized by powerful oxidants at high temperature and high concentrations of acid or base
O OH HN O 3 HO Cyclohexanone (k e to form) Cyclohexanone (e nol form) O OH O Hexanedioic acid (Adipic acid)

En el organismo los oxidantes y reductores utilizados son diferentes en su estructura a los usados comnmente en el laboratorio. La estructura indicada corresponde NAD+, un oxidante en el organismo. En la diapositiva que sigue aparece NAD+ con la palabra ad unida al anillo heterocclico para indicar la ribosa unida a ADP

Reduction
aldehydes can be reduced to 1 alcohols ketones can be reduced to 2 alcohols the C=O group of an aldehyde or ketone can be reduced to a -CH2- group
Aldehydes O RCH RCH3 Can Be Reduced to RCH2 OH Ketones O RCR' RCH2 R' Can Be Reduced to OH RCHR'

Hidrogenacin Catalitica
Ampliamente usada en la industria. Niquel Raney: Ni en polvo finamente dividido saturado con hidrgeno gas. Pt y Rh tambien se usan como catalizadores.

OH Raney Ni H

Catalytic Reduction
Catalytic reductions are generally carried out at from 25 to 100C and 1 to 5 atm H2
O + Cyclohe xanone H2 Pt 25 o C, 2 atm Cyclohe xanol OH

2 H2 OH 1-Butanol

H Ni trans- 2-Butenal (Crotonalde hyde)

Catalytic Reduction
A carbon-carbon double bond may also be reduced under these conditions
O 2 H2 OH 1-Butanol H Ni trans- 2-Butenal (Crotonalde hyde)

by careful choice of experimental conditions, it is often possible to selectively reduce a carbon-carbon double in the presence of an aldehyde or ketone

Metal Hydride Reduction

The most common laboratory reagents for the reduction of aldehydes and ketones are NaBH4 and LiAlH4
both reagents are sources of hydride ion, H:-, a very powerful nucleophile
H Na
+

H Li
+

H- B- H

H- A l- H

H: Hydride ion

H Sodium borohydride

H Lithium aluminum hydride (LAH)

Reduccin
Borohidruro de sodio, NaBH4, reduce C=O, pero no C=C. Hidruro de Litio y aluminio, LiAlH4, mucho ms fuerte, difcil de manejar Hidrgeno gaseoso con catalizador tambien reduce el enlace C=C.

NaBH4 Reduction
reductions with NaBH4 are most commonly carried out in aqueous methanol, in pure methanol, or in ethanol one mole of NaBH4 reduces four moles of aldehyde or ketone
O 4 RCH + NaBH4 methanol ( RCH2 O) 4 B Na A tetraalkyl borate
+

H2 O

4 RCH2 OH + borate salts

NaBH4 Reduction
The key step in metal hydride reduction is transfer of a hydride ion to the C=O group to form a tetrahedral carbonyl addition compound
H H O
+ Na H-B-H + R-C-R'

O BH3 Na R-C-R' H

H2 O OH R-C-R' H from water

from the h ydride re ducing agent

LiAlH4 Reduction
unlike NaBH4, LiAlH4 reacts violently with water, methanol, and other protic solvents reductions using it are carried out in diethyl O ether or tetrahydrofuran (THF)
4RCR + LiAlH4 ether H2O OH 4RCHR + aluminum salts

(R2CHO)4Al- Li+ A tetraalkyl aluminate

Clemmensen Reduction
refluxing an aldehyde or ketone with amalgamated zinc in concentrated HCl converts the carbonyl group to a methylene group
OH O Zn( Hg) , HCl OH

Wolff-Kishner Reduction
in the original procedure, the aldehyde or ketone and hydrazine are refluxed with KOH in a high-boiling solvent the same reaction can be brought about using hydrazine and potassium tert-butoxide in DMSO
O + H2 NN H2 Hydrazine KOH diethylen e glycol (reflux)

+ N 2 + H2 O

 A continuacin en la siguiente diapositiva se describe la reduccin en el organismo, mediante el reductor NADH, diferente en estructura a los utilizados en el laboratorio.

Formacin de hemiacetales cclicos en Carbohidratos

Cyclic hemiacetal formation

Figure 25.3

Haworth Projections
Haworth projections
five- and six-membered hemiacetals are represented as planar pentagons or hexagons, as the case may be, viewed through the edge most commonly written with the anomeric carbon on the right and the hemiacetal oxygen to the back right the designation - means that -OH on the anomeric carbon is cis to the terminal CH2OH; - means that it is trans

Haworth Projections
CHO H 2 OH HO 3 H H H 4 5 6 OH OH 1 6 CH2 OH OH H5 O H 4 OH H C 1 H HO 3 2 H OH anomeric carbon anomeric CH2 OH carbon O H H H + OH H HO OH( ) H OH -D -Glucopyranose ( -D -Glucose)

redraw

CH2 OH D -Glucose

CH2 OH O H OH ( ) H OH H HO H H OH -D-Glucopyranose (-D -Glucose)

Haworth Projections
six-membered hemiacetal rings are shown by the infix -pyran five-membered hemiacetal rings are shown by the infix -furan-

Furan

Pyran

Conformational Formulas
five-membered rings are so close to being planar that Haworth projections are adequate to represent furanoses
HOCH2 H OH( ) H HOCH2 H

H H

H H HO OH -D-Ribofuranose (-D -Ribose)

H OH( ) HO OH -D -Ribofuranose (-D-Ribose)

Conformational Formulas
for pyranoses, the six-membered ring is more accurately represented as a strain-free chair conformation
CH2 OH HO HO OH -D-Glucopyranos e (chair conformation) O OH ()

Conformational Formulas
if you compare the orientations of groups on carbons 1-5 in the Haworth and chair projections of -D-glucopyranose, you will see that in each case they are up-down-up-downup respectively
CH2 OH O H OH ( ) H OH H HO H H OH -D-Glucopyranose (Haworth projection) CH2 OH HO OH

HO

O OH ( )

-D -Glucopyranose (chair conformation)

Mutarotation
Mutarotation: the change in specific rotation that occurs when an or form of a carbohydrate is converted to an equilibrium mixture of the two
Monosaccharide -D-glu cose -D-glu cose -D-galactose -D-galactose [] after Mutarotation [] (degre es) (degre es) +112.0 +18.7 +150.7 +52.8 +52.7 +52.7 +80.2 +80.2 % Pres ent at Equilibrium 36 64 28 72

Haworth formulas for and -pyranose forms of D-glucose

Figure 25.4

Species present in aqueous solution of D-ribose

Figure 25.5

Mutarotation
HO HO CH2 OH O OH( )

OH -D-Glucopyranose [ ] D25 + 18.7 CH2 OH OH O HO C H CH2 OH O HO

HO HO

HO HO

Open-chain form

OH( ) -D-Glucopyranose [ ] D 25 + 112