Multicomponent
Reactions
MCR
Daniela Baumstark
xx.xx.2006
Definition
A MCR is a reaction, which delivers a
product by the reaction of at least 3
components.
„ The product has to show essential
structural elements of the educts.
„
History
„
1838: first MCR by Laurent and Gerhardt
CN
CHO
+
NH3
+
HCN
NH2
CHO
+
CN
N
History
1850: Strecker introduced the general
formation of α-aminocyanides
„ First documented MCR
„ S-3CR
„
NH3
+
HCN
+
CN
O
R
H
- H2O
R
NH2
History
„
1890: Hantzsch found a way to form
Pyridin- and Pyrrolderivates (Ha-3CR)
2 CH3COCH2CO2C2H5
H
Cl
O
+
H
O
H
+
NH3
COOR
+
O
R
H
H H
OO
H3C
CO2C2H5
HN
R
H3C
CO2C2H5
- H2O
COOR
COOR NH3
N
H
History
„
1893: Biginelli prepared Pyrimidinderivates
from aldehydes and urea (B-3CR)
R2
NH2
O
NH2
+
O
R1
R2
+
R3CHO
R1
HN
- 2 H2O
R3
N
O
H
History
„
1921:Passerini introduced the first MCRs
of the isocyanides (P-3CR)
R1NC
+
O
R2
OH
+
O
R3
R3
H
H
R1
N
O
O
O
R2
History
1934: Bergs and Bucherer introduced the
BB-4CR by adding CO2 to the S-3CR
„ First 4-Component-Reaction
„
O
R
NH3
+
HCN
+
O
R
H
+
CO2
- H2O
H
N
N
O
H
History
„
1958: Ugi et al. introduced the fourcomponent reaction of the isocyanides (U4CR)
R1NC
+
O
R2
H
+
H
R3
N
H
+
H
O
R4
OH
- H2O
R1
R2
N
O
N
O
R3
R4
Three types of MCRs
Type I: All subreactions are equilibrating
reactions
„ Type II: There is a equilibrium between
educts and intermediates, but the last step
is irreversible
„ Type III: All subreactions are irreversible
„
Biginelli-3CR
O
H2N
O
Ph
Ph
NH2
HO
H
H2N
O
Ph
Me
O H2N
NH
O
H
H+, -H2O
O
H
N
EtO
Ph
HO
+
NH
Me
EtO
O
Ph
EtO
Me
O
H2N
O
O
O
NH
N
H
O
Ph
EtO
-H2O
Me
NH
N
H
O
Passerini-3CR
O
R1
O
+
R2
R3
O
R1
R2
OH
H
H
O
O
O
R3
R4NC
O
R1
R2
O
R3
N
R4
O R1
R3
O
R2 R4
N
O
H O
H
O
R1
R2
O
N
R4
R3
Ugi-4CR
O
O
R1
+
H
NH2
R2
N
R1
R2
R3
H + R2
N
OH
H
+
R3
H
R1
N
R4
O
R
H
R
N
N
R
O
O
R
O
Advantages
Complexity
„ Diversity
„ No deprotection steps
„ Automation
„ Efficient solid phase or solution phase
synthesis
„
Disadvantage
„
No split-pool synthesis
References
„
„
„
„
„
„
http://www.priaton.de/Technologies/MCR_Chemistry/MCR_Definition/mcr_definition.h
tml
http://www.organic-chemistry.org/frames.htm?http://www.organicchemistry.org/Highlights/2005/05April.shtm
Pure Appl. Chem., Vol. 73, No. 1, pp. 187–191, 2001
http://www.oci.uni-hannover.de/AK_Kalesse/OCFvortraege05WS/Multikomponentenreaktionen.pdf
http://images.google.de/imgres?imgurl=http://www2.tju.edu.cn/colleges/pharmtier/img
/lige.gif&imgrefurl=http://www2.tju.edu.cn/colleges/pharmtier/html/chinese/publication/
ab/volume_one/ligeguotao.htm&h=180&w=445&sz=5&tbnid=2z8y4VXWeSzGJM:&tbnh=50&tbnw=124&
hl=de&start=6&prev=/images%3Fq%3DSplit%2Bpool%2Bsynthesis%26svnum%3D1
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Skript zur Vorlesung Kombinatorische Chemie und Festphasensynthese (part 5)