willgerodt‐kindler reacon · 2009. 2. 6. · with ammonium polysulfide, named aer conrad...
TRANSCRIPT
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Willgerodt‐Kindler Reac1on
Yong Guan Jan. 30, 2009
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Introduc5on
• The Willgerodt rearrangement or Willgerodt reac5on is an organic reac5on conver5ng an aryl alky ketone to the corresponding amide by reac5on with ammonium polysulfide, named aEer Conrad Willgerodt.
• The related Willgerodt‐Kindler reac5on takes place with elemental sulfur and an amine like morpholine. The reac5on is named aEer Karl Kindler.
Ar
O
n
HNR2, S8Ar NR2
Shydrolysis
heat n Ar OH
O
n
+ H2S + HNR2
(a) Willgerodt, C. Ber. Dtsch. Chem. Ges. 1888, 21, 534–536. (b) Kindler, K. Liebigs Ann. Chem 1923, 431, 187–207.
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Mechanism
Ar
O OHN
Ar
O N
O
H
protontransfer
Ar
HO N
O
H
- H2O NAr
HH
OS8
NAr
SH
O
H
protontransfer NAr
SH
O
H
keto-enoltautomerism NAr
SH
O
N O
Ar
HS
Ar
NSH
O
keto-enoltautomerism
ArN
S
O
ArOH
O
H2O
hydrolysis
Name Reactions and Reagents in Organic Synthesis, 2nd ed; Bradford P. Mundy, Michael G. Ellerd, Frank G., Jr. Favaloro; Wiley-Interscience, pp 690.
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Alipha5c Substrates
Cavalieri, L; Pattison, D. B.; Carmack, M. J. Am. Chem. Soc., 1945, 67,1783.
O
OO O
NH2(NH4)2Sx
20-50%
O
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Aroma5c Substrates
Darabi, H., et al. Tetrahedron Lett., 1999, 40, 7549.
OS8, morpholine
microwave S
NO
81%
OS8, morpholine
microwave S
NO
55-74%
G G
G=Cl, Me, NH2, OMe
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Darabi, H., et al. Tetrahedron Lett., 1999, 40, 7549.
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Prepara5on of Amides and Acids
DeTar, D. F.; Carmack, M. J. Am. Chem. Soc. 1946, 68, 2025. Davies, I. W., et al. J. Org. Chem., 2000, 65, 8415.
MeO2S
O1) S8, morpholine
2) NaOH MeO2S
COOH
57%
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Three Components Reac5ons
Kanbara, T., et al. Synlett, 2007, 17, 2687.
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Kanbara, T., et al. Synlett, 2007, 17, 2687.
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Three Components Reac5ons
Kanbara, T., et al. Synlett, 2007, 17, 2687.
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Three Components Reac5ons
Kanbara, T., et al. Synlett, 2007, 17, 2687.
The addition of a small amount of Na2S·9H2O into the reaction mixture of sulfur with aniline caused a color change of the reaction system, from pale yellow to deep blue
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Protected Carbonyl Compounds
Darabi, H., et al. Tetrahedron Lett., 2004, 45, 4167.
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Darabi, H., et al. Tetrahedron Lett., 2004, 45, 4167.
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Darabi, H., et al. Tetrahedron Lett., 2004, 45, 4167.
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Domino Reac5ons
Neckers, D. C., et al. J. Org. Chem., 2007, 72, 3122.
2-aminobenzo[b]thiophenes
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Neckers, D. C., et al. J. Org. Chem., 2007, 72, 3122.