PYRYLIUM IONS AND PYRONES
(chapt 7-9)
O
O
O
Pyrilium
Chromylium
Isochromylium
O
O
O
O
O
O
O
2-Pyrone
O
O
O
O
O
Coumarin
Isocoumarin
4-Pyrone
Chromone
PYRYLIUM IONS
O
O
O
O
Aromatic - Reactive
Counter ion often ClO4c.f.:
N
N
N
Electron deficient ring:
•No react. with electrophiles
•No react. with radicals
•Reaction with nucleophiles
•(Reacts in cycloadditions)
N
X=ClO4: 36 refs in SciFinder
X=BF4: 16 refs in SciFinder
X
O
Ph
Com. avail. (SciFinder) ca 170
Ar
Ar
Ar
O
R
R
O
R
Ar
R
R
R
Ar
O
R
R
O
Ar
R
O
Ar
Ar
Ar
Ar
ROrC
O
R
Ar
O
O
R
R
R
Ar
O
R
Ar
O
O
Ar
Ar
O
Ar
Ar
R
Ar
O
Ar
R
R
R
O
Ar
COrR
Ar
R
R
R
Ar
Ar
Ar
O
Ph
Com. avail. with 12 diff.
anoins
O
Ar
OR
OH
O
O
Ph
Ar
Ar
Ar
Ar
Ar
Ar
O
Ar
O
COrR
Reactions with nucleophiles
1,2-Add. - Ring opening!
Nu
Nu
O
O H
O
-H
O
Nu
Nu: Water, alcohols, ammonia, amines,
organometallics / carbanions, Wittig reagents
hydrides
Nu
Nu
1,4-add. common on flavylium
O
H Nu
O
Reactions with nucleophiles
ANRORC (add. of Nu., Ring Opening and Ring Closure)
Br
Br
NaNH2
Br
N
N
H NH2
H
N
NH2
N
NH2
NH
NH
H
XH2
O
O
X
H
H
HO X
H
H
- H2O
X
Nu = -XH2 (-NH 2, -CH2 R)
NH2
More stable aromatic rings
N
Good yields
CH2R
R
Availability starting material
NH2
N
Cycloadditions
1,3-Dipol
3-oxidopyryliums
O
O
O
O
O
O
EWG
EWG
Further transformations
to 7-membered rings
Pyrones
O
O
O
2-Pyrone
O
O
O
O
O
Coumarin
Isocoumarin
O
O
O
O
4-Pyrone
Chromone
OH pKa -0.3
Reactions with Electrophiles
O
HClO4
O
Me2SO4
ClO4
HClO4
O
O
O
OH Not stable
4-Pyrone
Me3OBF4
2-Pyrone
ClO4
O
OMe
O
O
OMe
No E-fil Ar Subst
Reactions with Electrophiles
E-fil Aromatic Substitution like products, but by other mechanisms
O2N
NO2
O
O
O
ONO2
O
O
Br2
Br H
Br
H
O O
+
Br
H
Br
H
O O
Br
-HBr
O
O
Reactions with Nucleophiles
lactone
H
Nu
O
Nu
OH
OH-, RMgX
O
O
O
O
NH3, amines CN-
NH3
O
O
O
H2N
H
O
O
OH
O
O
H
O
O OH
O
HO
O
H
H2N
HO
O -H2O
N
H
O
Reactions with Nucleophiles
Nu
O
O
1) RMgX
2) H+
RMgX
O
O
O
O
Nu
O
HClO4
R
- H2O
O
O
ClO4
O
O
H
O
NH3, amines OH-
HO R
NH3
O
H2N
O
H
H NH OH
2
-H2O
N
H
Cycloadditions
O
Diene in DA react.
O
EWG
EWG
O
O
Dienophile in DA
- CO2
EWG
H
O
O
O
[2+2] with tosyl isocyanate
O
O
C
N
O
O
O N Ts
N
Ts
N
Ts
Ts
O
- CO2
NH2
+
NH3
H /H2O
O
N
H
N
c.f. NH3 add to 4-pyrones
O
O
O
H
NH3
O
H2N O
H
H NH OH
2
O
-H2O
N
H
H
O
Synthesis - Pyrylium
HH
H
H
O
O
O
1) - H2O
2) [ox]
H
H
OH
O
H
OH
H
H
H
Cl
-HCl
O
H
H
O
O
H
H
O
H
H
H
-HCl O
Cl
O
O
-H2O
O
H
OH
1) - H2O
2) [ox]
O
Synthesis - Pyrylium
H
O
O
HH
O
- 2 H2O
O
H
O
O
HO
- 2 H2O
O
Synthesis - Pyrones
H
OH
H
H
O
O
O
O
OH
H
O - H2O
O
O
+
OH
H
O
OO
O
H
-H2O
O
H
O
O
O
H H
OH
OH
O
O
OR
O
- ROH
- H2O
O
O
Natural products etc.
O
O
O
Pyrilium Chromylium
Flavylium
Anthocyanines:
- Gycosides of polyhydroxyflavylium (Aglycon = anthocyanidin)
- Colored (red / violet / blue) pigments, red / blue flowers, blueberries, grapes (red wine) etc.
- Antioxidants - Polyphenols - Radical scavengers
O-β-D-glucose
O-β-D-glucose
HO
R=OH, R'=H: cyanin
R=R'=OMe: Malvin
R
O
OH
R'
Cyanidine / Cyanidol
OH
OH
OH
HO
O
OH
OH
HO
B
O
OH
B
OH
OH
O
O
HO
O
OH
O
Natural products etc.
O
O
O
O
O
O
4-Pyrone
Chromone
Flavon
Kawapyrones:
- Isolated from Káwa
- Relaxing drug used in Polynesia
OMe
Flavonoids:
- Gycosides of polyhydroxyflavon
- Colored (yellow) pigments in plants
- Antioxidants Polyphenols - Radical scavengers
OH O
OR
HO
O
OH
R=H: Quercetin
R= L-Rhamnose: Quercetrin
R= D-Glucose-L-Rhamsone: Rutin
O
O
'R
R
Rothenone
-Insecticide
-Parasites in rivers
OH
OH
O
O
OMe
OMe
O
H
Natural products etc.
O
O
O
2-Pyrone
O
Coumarin
Psoralenes
-Isolated from various plants
-Photochemotherapy against psoriasis
-[2+2] cycloadd. with cytosin / thymin in DNA
R
O
O
O
R'
R=R'=H: Psoralen
R=H, R'=OMe: Xantotoxin (8-MOP) Metoksalen - Geroxalen(R)
O
N
O
O
HN
O
N
NH2
R
HN
hν
N
O
O
R'
O
O
O
R
N
N
NH2
N
O
O
R'
O
O
Dicoumarol
-Anticoagulant - Vit K antagonist
-Sweet clower disease
O
Coumarin
OH
O
Sweet clover
(Melilotus
officinalis)
OH
Vit. K
R
O
OO
O
O
O
OH
Warfarin - Marevan®
CO2
O2C
HN
CO2
O
O
O
f. ex.
protrombin
Glu i f. ex.
deskarboksy protrombin
O
OH
O
R
R
OH
O
HN
Aflatoxines
-From Aspergillus flavus (fungus)
-Attacks nuts etc.
-Carcinogenic
O
CO2 , O2
Vit K-epoksid
Vit.-K 2,3-epoksid
reduktase
Vit K-hydrokinon
Vit.-K 2,3-kinon
reduktase
R
O
Vit K
(kinon)
O
Hemmes av
kumariner
O
R:
O
H
O
O
H
O
Aflatoxine B1