pyrylium ions pyrylium ions and pyrones aromatic - … · pyrylium ions and pyrones (chapt 7-9) o o...
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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 - Reactive
Counter ion often ClO4-
O
XX=ClO4: 36 refs in SciFinder
X=BF4: 16 refs in SciFinder
Com. avail. (SciFinder) ca 170 in 2007
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
ArO RR
Ar
O RR
OR
OPh
Ph
Ph
Com. avail. with 12 diff.
anoins
Nu: Water, alcohols, ammonia, amines,
organometallics / carbanions, Wittig reagents
hydrides
1,2-Add. - Ring opening!
1,4-add. common on flavylium
Reactions with nucleophiles
O
Nu
O
Nu
H - HO Nu
O Nu
O
Nu
O
H Nu
Nu = -XH2 (-NH2, -CH2R)
ANRORC (add. of Nu., Ring Opening and Ring Closure)
More stable aromatic rings
Good yields
Availability starting material
N
Br
N
Br
H NH2
N
Br
HNH2
N
NH2
H
NaNH2
NH
NH
N
NH2
N
CH2R
R
NH2
O O XH
HX
H
H
HOX
XH2
- H2O
Cycloadditions
3-oxidopyryliums
Further transformations
to 7-membered rings
O
O
O
O
1,3-Dipol
EWG
O
EWG
O
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
O O
2-Pyrone
Me3OBF4
O OMe
O OHNot stable
HClO4ClO4
E
E-fil Aromatic Substitution like products, but by other mechanisms
O O
NO2
O ONO2O O
O2N
Br2
O O
Br
H
HBr
+
O O
Br
HBr
H-HBr O O
Br
Reactions with Nucleophiles
O O
Nu
lactone
OH-, RMgX
O O O
O
OH OO
OHO OHO
OH
H
O ONu
NH3, amines, CN-
O O O
H2N
H O
H
OHOH2N
NH
ONH3
H
-H2O
O
O
Nu
RMgX
O
O1) RMgX
2) H+
O
HO R
O
RHClO4
- H2OClO4
O
O
Nu
NH3, amines OH-
O
O
O
O
H
H2NOH
O
HNH2
NH
O
NH3 H
-H2O
Cycloadditions
[2+2] with tosyl isocyanate
Dienophile in DA
O O
Diene in DA react.
EWG
O EWG
O
- CO2
EWG
O O O O
H
H
O
O C
N
O
Ts
O
NO
O
Ts
- CO2 O
NTs
c.f. NH3 add to 4-pyrones
N
NTs
H
H+/H2O
N
NH2
NH3
O
O
O
O
H
H2NOH
O
HNH2
NH
O
NH3 H
-H2O
Benzopyrilium
No E-fil Ar subst in benzene ring
(in contrast to (iso)quinolines)O
O
Chromylium Isochromylium
O
Flavylium
Nu
Ph
Selectivity?•ROH at C-4 u. mild cond
•Ammonia / amines mixt
•Soft carbanions at C-4
•NB! C-2 attack leads to ring opening
Benzopyrones
O O
Coumarin
O
Isocoumarin
O
O
O
Chromone
O
O
OO
O
H+ / E+
OH
intermed. strongly acidic cond.
O
O
E
(also subst. in benzene ring for coumarines u. acidic cond)
O OO
O
Reacts with E-files u neutral conditions
React with E-files
React with Nu-files
O OO
O
Reacts with Nu-files
(ring openings)
Metallation
O
O
LDA
O
O
LiE
Synthesis - Pyrylium
O O
HH
H
O
HH
OH
1) - H2O2) [ox]
O
H
H
H
H
O
Cl
H H
O
O
ClO
H
O O-H2O-HCl -HCl
H
OH O
HH
O
HH
OH
1) - H2O2) [ox]
O
H
Synthesis - Pyrylium
O
H O
O
HH
- 2 H2O O
O
H O
- 2 H2OO
HO
Synthesis - Pyrones
O
HH
O OH
O
H
O O
OH
H
O O- H2O
OH O OH
O
H
+
O O
O
OOHH
OO-H2O
OH
O
H H
OR
O
O
O
- ROH
- H2O
Natural products etc.
O O
Pyrilium Chromylium
O
OH
HO
OH
OH
OH
Cyanidine / Cyanidol
B
O
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-!-D-glucoseO-!-D-glucose
R
OHR'
R=OH, R'=H: cyaninR=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: Quercetin
R= L-Rhamnose: Quercetrin
R= D-Glucose-L-Rhamsone: Rutin
Kawapyrones:
- Isolated from Káwa
- Relaxing drug used in Polynesia
Rothenone
-Insecticide
-Parasites in rivers
O
O
OO
H
H
OMe
OMe
O
OMe
O
R
R'
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
h!
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
OH
H
Aflatoxine B1
Sweet clover
(Melilotus
officinalis)
O
O
R
Vit K(kinon)
OH
OH
R
Vit K-hydrokinon
O
O
R
Vit K-epoksid
O
Vit.-K 2,3-epoksid reduktase
Vit.-K 2,3-kinonreduktase
CO2
O
HN
Glu i f. ex.deskarboksy protrombin
CO2
O
HN
f. ex.protrombin
O2C
CO2, O2
Hemmes av kumariner
R: