Reaes de Adio Ligao Mtipla Carbono-Carbono Carbono-

QUMICA ORGNICA FUNDAMENTAL 2005/2

Orbitais moleculares sp2 - Molcula de eteno

electrostatic potential map

Orbitais moleculares sp Molcula de etino

Adies sin e anti

C C + A B addition A C C B

+ X

Y X

C Y

A syn addition

Y C C + X Y X C C A anti addition

Reaes de Adio: Hidrogenao Cataltica

C C + H H cat. H H C C + calor

H2 catalisador

H H

C C

H H

C C

hidrognio adsorvido no cat.

Complexo alqueno-cat.

C C H H

C C H

catalisador regenerado

O papel do catalisador

Mecanismo da hidrogenao cataltica

Alguns aspectos especiais da hidrogenao

CH3 CH3 + H2
Pt, 1 atm 25oC

CH3 CH3 H H (adio sin)

H2, Pd

H3C

CH3

H H3C
Pd, 1 atm

H CH3 CH3 C C CH3

CH3C CCH3

H2

(Lindlar) Pd/CaCO3/Pb

H H cis-2-Buteno C C CH2CH3

CH3CH2C CCH2CH3
O Ni OCCH 3
2

H2/Ni2B

CH3CH2

H H (Z)-3-Hexeno
NaBH 4 C2H5OH Ni2B P-2

H3C

CH3
H2 Pd/C

H3C

CH3

CH3 H H H

H3C

CH3 H H H CH3 no se forma

CH3

Adio anti de hidrognio: sntese de alquenos trans

CH3(CH2)2 C C (CH2)2CH3 1. Li, C2H5NH2, 78oC 2. NH4Cl CH3(CH2)2 C H C (CH2)2CH3 H

4-Octyne

(E)-4-Octyne (trans-4-Octyne) (52%)

R


Li

NHEt

R C C

R R Radical anion Vinylic radical A lithium atom donates an electron to The radical anion acts as a base and removes a the T bond of the alkyne. An electron proton from a molecule pair shifts to one carbon as the of the ethylamine. hybridization states change to sp2. R C C R H Li


R C C

H R H NHEt

R C C

R H Vinylic radical trans-Vinylic anion trans-Alkene The anion acts as a base and A second lithium atom donates an electron to removes a proton from a second molecule of ethylamine. the vinylic radical.

O
H2 Pd/C etanol

Hidrogenao cataltica de outros grupos funcionais

CO2Me

CO2Me

H2 Pd/C etanol

H2, cat. altas temperaturas e presses

Br
H2, Pd/CaCO3 KOH alcolico

HBr

Br

H2, Pt 25oC

HBr

Ni-Raney

S O

H2 SH

CH3CH2CH2CH3

H2S

S
SH BF3

Ni-Raney H2

Hidrogenao na indstria alimentcia e em sistemas biolgicos

O O
H2 Pd/C

c. linoleico (const. do leo vegetal)

O O

c. esterico (gordura saturada - margarina)

H H HO2C C C CO2H H H c. succnico + Enzima

Desidrog. Hidrog.

HO2C C=C H

H CO2H

c. fumrico + Enzima-H2 Enzima = Desidrogenase succnica

Calor de hidrogenao
C C + H H Pt C H C H
(H 120 kJ mol1

CH3CH2CH
H3C C C

CH2 + H2 1-Butene (C4H8)

CH3 + H2 Pt

Pt

CH3CH2CH2CH3 Butane
CH3CH2CH2CH3 Butane

(Ho = 127 kJ mol-1

(Ho = 120 kJ mol-1

H H cis-2-Butene (C4H8)

H3C C C

H + H2 Pt CH3CH2CH2CH3 Butane (Ho = 115 kJ mol-1

CH3 H trans-2-Butene (C4H8)

Padro de estabilidade relativa dos alquenos, com base no calor de hidrogenao

trans-2-butene > cis-2-butene > 1-butene.

H3C C=C H

CH3 H

E.P. H C=C H3C H (menos energtico) (H = - 27,6 Kcal/mol CH3 cis trans
(H trans (H cis

(mais energtico) (H = - 28,6 Kcal/mol

Curso da reao

R R

R > R

R R

R > H

R R

H > H

R H

H > R

R H

R > H

R H

H > H

H H

H H

Tetrasubstituted

Trisubstituted

Disubstituted

Monosubstituted Unsubstituted

ndice de Deficincia de Hidrognio (IDH)

Alcano: CnH2n + 2 Alquenos e cicloalcanos: CnH2n Alquinos e alcadienos: CnH2n - 2 IDH = Nmero de pares de hidrognio que devem ser subtrados da frmula molecular do alcano correspodente, afim de se obter a frmula molecular do hidrocarboneto considerado. Hexano C6H14 Hexeno C6H12 H2 ( 1 par)

IDH = 1

Consideraes Importantes na Utilizao dessa Metodologia

I. Presena de elementos do Grupo VI (O, S, Se, Te) - Ignorar o heterotomo e comparar a frmula resultante com o alcano correspondente:
O

C7H14O2

C7H14

C7H16 CnH2n + 2

( 2 H, IDH = 1)

Acetato de isopentila II. Presena de elementos do Grupo VII (F, Cl, Br, I) - Substituir o halognio por hidrognio (na prtica acrescentar um H por cada halognio) e comparar a frmula resultante com o alcano correspondente:

C2H3Cl3O2

C2H6

C2H6 CnH2n + 2

IDH = 0 Cloral

OH H OH

Cl3C C

III. Presena de elementos do Grupo V (N, P, As, Sb, Bi) - Subtrair um hidrognio para cada heterotomo e comparar a frmula resultante com o alcano correspondente:

C10H14N2

C10H12

C10H22 ( 10 H, IDH=5) CnH2n + 2

N N

Nicotina

Alternativamente o IDH pode ser calculado por:

IDH = 1 + 7[(no tomos do elemento particular) (NL 2)] 2 Considerando uma substncia contendo C, H, N, O e Cl; e as correspondentes nmero de ligaes (NL) O = 2, C = 4, N = 3, Cl = 1, temos: IDH = 1 + [nC x 2 + nH x (-1) + nN x 1 + nCl x (-1)] 2 IDH = 1 + nC - nH + nN - nCl 2 2 2 Exerccio: Calcular o IDH dos exemplos acima (acetato de isopentila, cloral e nicotina), sabendo-se que as frmulas moleculares so: C7H14O2, C2H3Cl3O2, C10H14N2 , respectivamente.

Exerccio
O cariofileno, composto encontrado no leo de cravo, tem a frmula molecular C15H24 e no tem ligao dupla. A reao do cariofileno com excesso de hidrognio, na presena de catalisador de platina, leva ao composto com a frmula C15H28 . (a) Quantas duplas ligaes tem o cariofileno? (b) quantos anis tem a molcula?
CH3O RO Eugenol: R = H Acetato de eugenila: R = Ac Cariofileno

Adio de X-Y a alquenos XC C + X Y C X T bond W bond C Y

2W bonds Bond formed

Bonds broken

Mecanismo geral da adio de HX (X = F, Cl, Br ou I)

1a Etapa

H C C + H X slow
+C

X

The T electron of the alkene form a bond with a proton from HX to form a carboncation and a halide ion.
H
2a Etapa

H fast C C

X The halide ion reacts with the carboncation by donating an electron pair; the result is an alkyl halide.
Ordem de reatividade: HI > HBr > HCl > HF

Parmetros cinticos e termodinmicos

H X H + C C C C+ + X

Electrophile Nucleophile

H C C
+

H + X C

X C

Electrophile Nucleophile

v = k[alqueno][HX]2 Diagrama de energia livre para adio de HX alquenos.

Regioqumica da adio de HX
H2C=CH2
H C H C H H

HBr
H H C H C

H3CCH2Br
H H C C H H

H Br

H H

Br

Br

H2C

CHCH3 +

HBr

CH3CHCH3 Br 2-Bromopropane

(little BrCH2CH2CH3) 1-Bromopropane

CH3

H3C C H3C 2-Methylpropene (isobutylene) CH2 + HBr H3C

CH3 C CH3 Br tert-Butyl bromide

(little H3C CH CH2 Br ) Isobutyl bromide

Regiosseletivdade - Regra de Markovnikov

1870: Vladimir Markovnikov (qumico russo) props a seguinte regra: If an unsymmetrical alkene combines with a hydrogen halide, the halide ion adds to the carbon atom with fewer hydrogen atoms (The addition of HX to an alkene, the hydrogen atom adds to the carbon atom of the double that already has the greater number of hydrogen atoms).
Carbon atom with the greater number of hydrogen atoms CH2 CHCH3 H Br
H X H + CH3CH CH2 CH3CH CH2 + 1o Carbocation (less stable)
CH3CH
+

CH2 H

CHCH3 Br

X

CH3CH CH2 + H

CH2 H +

X

2o Carbocation (more stable)

X CH3CH CH 2 HBr slow

CH3CH2CH2 1o
+

Br

CH3CH2CH2Br 1-Bromopropane (little formed)

CH3CHCH3 2 Step 1
o

Br

CH3CHCH 3

Br 2-Bromopropane (main product) Step 2

Diagrama de energia livre para adio de HBr ao propeno (G(2) menor que (G(1).

Postulado moderno para a regra de Markovnikov

In the ionic addition of an unsymmetrical reagent to a double bond, the positive portion of the adding reagent attaches itself to a carbon atom of the double bond so as to yield the more stable carbocation as an intermediate.
H3C C H3C 2-methylpropene
H+ H

H3C
+C

CH3 CH2 Cl  I H3C C Cl 2-Chloro-1-iodo-2-methylpropane CH2 I

CH2 + I

Cl

H3C

Exceo regra de Markovnikov Adio de HX na presena de perxidos

CH3CH

CH2 + HBr

ROOR

CH3CH2CH2Br

Estereoqumica da adio de HX
CH3CH2CH CH2 + HX * CH3CH2CHCH3 X
(a) H C2H5 CH CH2 H X
 C2H5 C+ + X

(a)

X C2H5 C H CH3

(S)-2-Halobutane (50%) (b) H CH3

CH2

H Achiral, trigonal planar carbocation 1-Butene accepts a proton from HX to form an achiral carbocation.

(b)

C2H5 C

X (R)-2-Halobutane (50%) The carbocation reacts with the halide ion at equal rates by path (a) or (b) to form the enantiomers as a racemate.

Adio de cido sulfrico a alquenos

O C C +H O S O
Alkene Sulfuric acid Carbocation

H OH
+C

O +


HO3SO OH C

H C

S O

Hydrogen sulfate ion Alkyl hydrogen sulfate

Soluble in sulfuric acid

H C H3C H CH 2 OSO 3H H
+C

H CH 2 H OSO H 3 H3C C CH 3

H3C

OSO 3H Isopropyl hydrogen sulfate

2o Carbocaion (more stable carbocation)

H2O, heat

Isopropyl alcohol

Adio de H2O catalisada por cido - Hidratao

C C + HOH H3 O+ C H H2C CH2 + HOH H3PO4 300 C
o

C OH

CH 3CH2OH
OH

H3O+

Mecanismo da hidratao
CH3 H 3C C CH2 H H O
+

1a

Etapa

slow

H 2C H 3C C+

H +

H O H

CH3 CH3H H3C C O

+

2a Etapa

CH3 H3C C+ CH3 +

H O H

fast

CH3
3a Etapa
H3C CH3H C CH3 O
+

H H + O H fast H3C

CH3 C CH3 O H + H

H O
+

Regioqumica e rearranjos
H3C C CH2 + HOH H3C 2-Methylpropene (isobutylene)
CH 3 H3C C CH 2 H H O
+

H3O
o

CH3 H3C C CH2 H

25 C

OH tert-Butyl alcohol
very slow CH 3 H3C C H + CH 2+ H O H

Praticamente no ocorre

CH 3 H3C C CH CH2 CH 3 3,3-Dimethyl-1-butene

H2SO4 H2O

OH H3C C CH CH3

CH3 CH3 2,3-Dimethyl-2-butanol (major product)

Adio de X2 a alquenos
CH3CH2CH CH2 + Cl2 9oC CH3CH2CH Cl CH2 (97%) Cl

CH3CH

CHCH 3 +

Cl2

9 C

CH3CH Cl

CHCH 3 (100%) Cl

Br2

Br 5 C H + enantiomer (95%) H CCl4 Br trans-1,2-Dibromocyclohexane (as a racemic form)

o

Utilizao clssica Caracterizao de alquenos e alquinos

room temperature in the dark, CCl4

+ Br2

An alkene Bromine (colorless)(red brown)

Br Br vic-Dibromide (colorless)

Rapid decolorization of Br2/CCl4 is a test for alkenes and alkynes.

Br2 + R H Alkane Bromine (colorless) (red brown)

room temperature in the dark, CCl4

no appreciable reaction

Mecanismo da adio de X2
1a Etapa

C
+

C Br

Br  Bromide ion

H Br H Br

Bromonium ion

Br

Br C
+ Br


Br C C + Br 

Br

Bromonium ion

2a Etapa

Br C C + Br  Br Bromide ion vic-Dibromide C C Br + Bromonium ion

Estereoqumica da adio de X2
H H H Br2 CCl4 Br + enantiomer H H

Br H trans-1,2-Dibromocyclopentane

Br  H Bottom attack

H
+

H H

H Br Br

Br

Br+

Br Br cis-1,2-Dibromocyclopentane (not formed)



Cyclopentene

Carbocation intermediate
Br 

Br

Br

Br

(b)

(b) (a)

Top Br H attack trans-1,2-Dibromocyclopentane

H Br

(a)

Br

Br+ Bromonium ion

Br

trans-1,2-Dibromocyclopentane enantiomers

Br  Br2
6 1 2 3 6 1 2 3

inversion at C1

Br

Cyclohexene

Br + Bromonium ion inversion at C2 Br Br

Br Diaxial conformation trans-1,2Dibromocyclohexane

Br Br Br Diequatorial conformation

Br

trans-1,2-Dibromocyclohexane

Reaes estereoespecficas
H3 C H C C H Br2 CH3 CCl4 Br CH3 H C C Br H

trans-2-Butene

CH3 (2R,3S)-2,3-Dibromobutane (a meso compound)

Br Me H C
+

Me H H Me Br

Br C C H Me

C


Me C H

H Me

Br

Br Me H C

Br C
+

trans-2-butene

H Me

Br C Me H C

Me

Br

Br

anti-addition

H3 C H3 C

C C

H Br2 H CCl4

Br H

CH3 H C C Br

CH3 H Br C C Br H

cis-2-Butene

CH3 (2S,3R)

CH3 (2S,3S)

Br H Me H C C H Me Me cis-2-butene Br Br H Me C
+

Me H Me

H C C

Br H Me

C


Br + Br H Me C C

Br C Br

H Me

Me

Br

anti-addition

(a) Br  (b) (a) H H CH3 H 3C C C Br

+

Br H H 3C C C

HCH 3 Br

H H3C

H CH3

H Br H Br

Bromonium ion (achiral)

(2R,3R-)2,3-Dibromobutane (chiral) Br H H3C (b) C C H CH3 Br (2S,3S)-2,3-Dibromobutane (chiral)

cis-2-butene reacts with bromine to The bromonium ion reacts with the yield an achiral bromonium ion and bromide ions at equal rates by paths (a) a bromide ion. [Reaction at the and (b) to yield the two enantiomers in other face of the alkene (top) would equal amounts (i.e., as the racemic form). yield the same bromonium ion.]

(a) Br  (b) (a) H CH3 H3C C C H Br

+

Br H H3C C C

CH3 H Br

H H3C

CH3 H

H Br H Br

Bromonium ion (chiral)

(R,S-)2,3-Dibromobutane (meso) Br H H3C (b) C C CH H 3 Br (R,S)-2,3-Dibromobutane (meso)

trans-2-Butene reacts with bromine yo yield chiral bromonium ions and bromide ions. [Reaction at the other face (top) would yield the enantiomer of the bromonium ion as shown here.]

When the bromonium ions react by either path (a) or path (b), they yiled the same achiral meso compound. [Reaction of the enantiomer of the intermediate bromonium ion would produce the same result.]

Adio de X2/H2O Formao de halohidrinas

C C + X2 + H2O X = Cl or Br C C + C C + HX

X OH Halohydrin (major)
C C X
+

X X vic-Dihalide (minor)
C + X

1a Etapa

C
H X H X

Halonium ion

This step is the same as for halogen addition to an alkene

2a e 3a Etapa
C X
+

H C + O H H X C C

H H O H X H C C O + H O H
+

Protonated Halohydrin halohydrin The protonated hallohydrin loses a Here, however, a water molecule acts as the nuclephile and attacks a proton (it is transferred to a molecule of water). This step produces the carbon of the ring, causing the halohydrin and hydronium ion. formation of a protonated halohydrin.

Halonium ion

Regiosseletividade
H3C C H3C CH2 Br2 CH3 H3C
H

CH2 Br H

OH2

+OH2

H3C

C CH3

CH2Br H3C

H OH C CH2Br

Mapa de contorno vermelho indica rea relativamente negativa e azul indica reas relativamente positiva (ou nemos negativa).

CH3 (73%)

The Sea: A Treasury of Biologically Active Natural Products

Br Cl Cl Br Cl

Cl

Cl

Cl Cl

Halomon: in preclinical evaluation as a cytotoxic agent against certain tumor cell types
OCH 3 Br
3

Tetrachloromertensene

Br Br OH Br O

Cl

(3R)- and (3S)-Cyclocymopol monomethyl ether: show agonistic or antagonistic effects on the human progesterone receptor, depending on which enantiomer is used

Dactylyne: an inhibitor of pentobarbital metabolism

Br Cl Br

O O Br

Kumepaloxane: a fish antifeedant synthesized by the Guam bubble snail Haminoea cymbalum, presumably as a defense mechanism for the snail.

(3E)-Laureatin:

HO H O O O H H O H H O H H O H O H O H H O H H H O O

H O

Brevetoxin B: associated with deadly red tides.