pyrylium ions and pyrones (chapt 7-9). electron deficient ring: no react. with electrophiles no...
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PYRYLIUM IONS AND PYRONES(chapt 7-9)
O OO
O O O
O
Pyrilium Chromylium Isochromylium
2-Pyrone 4-Pyrone
O O
Coumarin
O
IsocoumarinO
O
O
Chromone
O
O
Electron deficient ring: No react. with
electrophiles
No react. with radicals
Reaction with nucleophiles
(Reacts in cycloadditions)
O O O O
PYRYLIUM IONS
N N N Nc.f.:
Aromatic - ReactiveCounter ion often ClO4
-
OX X=ClO4: 36 refs in SciFinder
X=BF4: 16 refs in SciFinder
Com. avail. (SciFinder) ca 170
OAr
Ar
O RRO ArArOAr
OAr
Ar
R
R O ArAr
Ar
Ar
O RR
R R
O ArAr
Ar
Ar Ar
O ArAr
Ar
O ArAr
R
O RR
Ar
OAr
Ar
O RR
R
O RR
OH
O COrRROrC
Ar
O COrRAr
Ar
R
ArOAr
Ar
Ar O RR
Ar
O RR
OR
OPh
Ph
Ph
Com. avail. with 12 diff. anoins
Reactions with nucleophiles
O
Nu
ONu
H - HO Nu
O Nu
Nu: Water, alchohols, ammonia, amines, organometallics / carbanions, Wittig reagents hydrides
1,2-Add. - Ring opening!
O
Nu
O
H Nu1,4-add. common on flavylium
Reactions with nucleophiles
Nu = -XH2 (-NH2, -CH2R)
O
XH2
O XH
H XH
HHO
- H2O X
NH2N
CH2R
R
ANRORC (add. of Nu., Ring Opening and Ring Closure)
N
Br NaNH2N
Br
H NH2
N
Br
HNH2
NNH2
HNH
NH
N
NH2
More stable aromatic rings
Good yields
Availability starting material
O
O
O
O
1,3-Dipol
EWG
O
EWG
O
Cycloadditions
3-oxidopyryliums
Further transformations to 7-membered rings
O O
2-Pyrone
HClO4
Me3OBF4
O OMe
O OH
ClO4
Not stable O
O
4-Pyrone
HClO4
Me2SO4
O
ClO4
OH pKa -0.3
O
OMe
No E-fil Ar Subst
Pyrones
Reactions with Electrophiles
O O
O
O
2-Pyrone
4-Pyrone
O O
Coumarin
O
IsocoumarinO
O
O
Chromone
O
O
E-fil Ar Subst prod. by other mechanisms
O O
NO2O ONO2
O O
O2N
Br2
O O
BrH
HBr
+
O O
Br
HBr
H-HBr O O
Br
Reactions with Electrophiles
Reactions with Nucleophiles
O O
OH
OO
OH OO
OH
H
O OHO
O ONH3
OH2N
H OH
OHOH2N
H
-H2O NH
O
O O
Nu
lactone
OH-, RMgX
O ONu
NH3, amines CN-
Reactions with Nucleophiles
O
O1) RMgX
2) H+
O
HO R HClO4
- H2O O
R
ClO4
O
O
NH3O
O
H
H2NH
OH
O
H NH2-H2O N
H
O
O
ONuRMgX
O
O
Nu
NH3, amines OH-
Cycloadditions
O O
Diene in DA react.
EWG
O EWG
O
- CO2
EWG
O
O C
N
O
Ts
O
NO
O
Ts
- CO2 O
NTs
NH3
c.f. NH3 add to 4-pyrones
N
NTs
H
H+/H2O
N
NH2
[2+2] with tosyl isocyanateO O O O
H
H
Dienophile in DA
O
O
NH3O
O
H
H2NH
OH
O
H NH2-H2O N
H
O
Synthesis - Pyrylium
HH
H
O
Cl
H H
O
O
ClO
H
O -H2O-HCl -HCl
H
O
OH O
HH
O
HH
OH
H1) - H2O2) [ox]
O
O O
H HH
O
HH
OH
H1) - H2O2) [ox]
O
Synthesis - Pyrylium
O
H O
O
HH
- 2 H2O O
O
H O
- 2 H2OOHO
Synthesis - Pyrones
O
HH
O OH
OH
O O
OH
HO O- H2O
OH O OH
OH
+
O O
O
O
-H2O
OHH
OO OH
O
H H
OR
OO
O
- ROH- H2O
Natural products etc.
O O
Pyrilium Chromylium
O
OH
HO
OH
OH
OH
Cyanidine / Cyanidol
BO
O
OH
HO
OH
OH
B
O
O
OH
HO
O
OH
O
Anthocyanines:
- Gycosides of polyhydroxyflavylium (Aglycon = anthocyanidin)
- Colored (red / violet / blue) pigments, red / blue flowers, blueberries, grapes (red wine) etc.
- Antioxidants - Polyphenols - Radical scavengers
OHO
O-β- -D glucose-O β- -D glucose
R
OHR'
= , = : R OH R' H cyanin= = : R R' OMe Malvin
Flavylium
Natural products etc.
O
O
O
O
4-Pyrone Chromone
O
O
Flavon
Flavonoids:
- Gycosides of polyhydroxyflavon
- Colored (yellow) pigments in plants
- Antioxidants Polyphenols - Radical scavengers
O
OOH
HO
OR
OH
OH
R=H: QuercetinR= L-Rhamnose: QuercetrinR= D-Glucose-L-Rhamsone: Rutin
O
OMe
O
R'R
Kawapyrones:
- Isolated from Káwa
- Relaxing drug used in Polynesia
Rothenone-Insecticide-Parasites in rivers
O
O
OO
H
H
OMeOMe
Natural products etc.
OO O
R
R'
R=R'=H: Psoralen
R=H, R'=OMe: Xantotoxin (8-MOP) -
Metoksalen - Geroxalen (R)
Psoralenes-Isolated from various plants-Photochemotherapy against psoriasis-[2+2] cycloadd. with cytosin / thymin in DNA
OO O
R
R'
HN
N
O
O
OO O
R
R'
HN
N
NNO
O NH2
ONN
NH2
O
hν
O O
2-Pyrone
O O
Coumarin
O O O
OHOH
O
Dicoumarol-Anticoagulant - Vit K antagonist-Sweet clower disease
O O
OH
O
Warfarin - Marevan®
O
O
R
Vit. K
Aflatoxines-From Aspergillus flavus (fungus)-Attacks nuts etc.-Carcinogenic
O O
Coumarin
O O
O
O
OHH
Aflatoxine B1
Sweet clover(Melilotus officinalis)
O
OR
Vit K(kinon)
OH
OHR
Vit K-hydrokinon
O
OR
Vit K-epoksid
O
Vit.-K 2,3-epoksid reduktase
Vit.-K 2,3-kinonreduktase
CO2
OHN
Glu i f. ex.deskarboksy protrombin
CO2
OHN
f. ex.protrombin
O2C
CO2, O2
Hemmes av kumariner
R: