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PRCTICA I.10
ANLISE DO IBUPROFENO RACMICO E
(S)-IBUPROFENO POR FORMAO DE
DERIVADOS DIASTERIOISOMRICOS
INTRODUO GERAL
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CH3
CH3
N
1)
N
N
COOH
R
H
CH3
N
CO2
N
N
H2N
2)
(2R)-ibuprofeno
1,1'-Carbonildiimidazol
CH3
N
+
CH3
CH3
(S)-(-)--metilbenzilamina
CH3
CH3
N
1)
N
N
COOH
R
H
CH3
N
2)
(2S)-ibuprofeno
1,1'-Carbonildiimidazol
CH3
N
+
N
+
H2N
R
CH3
CH3
(S)-(-)--metilbenzilamina
CH3
R=
CH3
TCNICA
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CO2
gua. Seque a fase orgnica com sulfato de sdio anidro e elimine os solventes por
evaporao em evaporador rotativo.
Proceda a uma anlise por CCF (gele de slica 60 F254; Clorofrmio:ter de petrleo
6080, 7:3) do(s) produto(s) sintetizado(s), assim como de solues clorofrmicas de
(2S,2R)-ibuprofeno e (2S)-ibuprofeno.
REAGENTES E MATERIAL
1.
2.
OBJECTIVOS PEDAGGICOS
estudantes a contactar com tcnicas que permitam diferenciar uma mistura racmica de
um dos enantimeros. A tcnica seleccionada estava j descrita na literatura [2], no
entanto a anlise das amidas diasterioisomricas era realizada por RMN de 1H. Na
medida em que RMN constitui um mtodo que no acessvel a muitos laboratrios de
Qumica Farmacutica, efectuou-se a anlise das amidas sintetizadas por mtodos
cromatogrficos.
Madalena M. M. Pinto
madalena@ff.up.pt;
Honorina M. M. Cidade
hcidade@ff.up.pt
trabalho
em
laboratrios
de
Qumica
Medicinal
requer
vidrarias
de
solventes
no
representam
problemas
documento
foi
supervisionado
CIDADE(hcidade@ff.up.pt)
pelo
Prof.
HONORINA
inflamabilidade,
riscos
de
exploso,
etc.),
Se
seu
exerccio
ou
prtica
envolver
qualquer
risco
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EXERCISE I.10
ANALYSIS OF RACEMIC IBUPROFEN AND
(S)-IBUPROFEN BY THE FORMATION OF
DIASTEREOISOMERIC DERIVATIVES
Honorina Cidade and Madalena Pinto
Laboratrio de Qumica Orgnica, Faculdade de Farmcia,
Universidade do Porto, Rua Anbal Cunha, 164 4050-047 Porto,
Portugal
E-mail: madalena@ff.up.pt
INTRODUCTION
Materials
Precoated silica gel 60 F254 (Merck) TLC plates were used for TLC analysis. (2R,2S)ibuprofen was purchased from Sigma Chemical Co. (2S)-ibuprofen and S-()-methylbenzylamine were obtained from Aldrich, and 1,1'-carbonyldiimidazole was
obtained from Fluka.
Methods [2]
The sample (50 mg) is dissolved in 0.9 mL of chloroform in a round-bottom flask. 0.3
mL of a solution of 1,1'-carbonyldiimidazole (0.14 g/mL in chloroform) is added
dropwise, and the solution is stirred for 5 min at room temperature. 31 L of (S)-()-methylbenzylamine is then added by an automatic pipette to the reaction mixture. The
solution is stirred for an hour at room temperature. The reaction is quenched by an
addition of 3 mL of hexane and then washed with 2 4 mL of a solution of sodium
bicarbonate (5 %), 2 4 mL of 1 M hydrochloric acid, 2 4 mL of a solution of sodium
bicarbonate (5 %), and finally with 2 4 mL of water. After drying the organic layer
with anhydrous sodium sulfate, the solution is evaporated to dryness to obtain the crude
amide mixture, which is analyzed by TLC (silica gel 60F254; chloroform:petroleum
ether 6080, 7:3).
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1)
COOH
CH3
CH3
N H
CO2
N
(2R)-ibuprofen
N
CH3
2) R
CH3
H2N
R
CH3
N H
CH3
(S)-(-)--methylbenzylamine
1)
COOH
2) R
N H
CO2
(2S)-ibuprofen
1,1'-carbonyldiimidazole
N
N
CH3
CH3
CH3
CH3
H2N
R
CH3
N H
CH3
(S)-(-)--methylbenzylamine
CH3
R=
CH3
REFERENCES
1.
2.
Madalena Pinto
madalena@ff.up.pt
your
exercise
involves
any
special
risks,
please
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