DIAZINES

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DIAZINES
Only C-5 in pyrimidine NOT elctron def.
Diazines -Reacts even less readily with
electrophiles than pyridine -Reacts easily with
nucleophiles (additions / substitutions) -Reacts
with nucleophilic radicals (Minisci) -Reacts as
dienes in DA cycloadd. (less aromatic than
pyridine)
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Reactions with electrophiles
-Protonation -N-alkylation -Ox. to N-oxides
(H2O2, peracids) -Pract. no E-fil Ar subst. (C-5
pyrimidine) -Halogenation by add. / elim.
mechanisms
c.f. pyridines
weaker bases than pyridine
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Reactions with nucleophiles
Addition - Rearomatization
RMet RLi, RMgX ox DDQ, KMnO4
1,2- add 1,4-add
Add. av NH2- (Chichibabin)
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Substitution on halodiazines
Nucleophiles -ammonia / amines -thiolates -malona
tes etc. -water / alchohols / alchoxides
Leaving groups -halogen -OMe -SO2Me
rel. soft
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With hard Nu
Pd-cat. couplings
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Metallation
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Radical reactions (Minisci)
Cycloadditions (DA)
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Oxydiazines
Structure - Tautomerism
React. with E-files
More electron rich, reacts easier with E-files
than diazines OH o/p directing
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React. with Nu-files
Nu Ar subst
More complex mech.
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Undheim - Metaphase Inhibitors
Metaphase
Prophase
Anaphase
Telophase
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N-Deprotonation / Alkylation
O-silylation / N-alkylation
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N-Deprotonation / Alkylation
N-alkylation / C-alkylation
N-alkylation / O-alkylation
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C-Deprotonation / Metallation
Excess base Because of NH
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Replacement of oxygen
Halogenation
Oxo ? thio
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Cycloadditions
Cancer
Psoralenes - Psoriasis
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Aminodiazines

• Exists as aminodiazines (not imino)
• -NR2 electron donor Stronger bases
• -NR2 electron donor Participates easier in E-fil
  Ar subst.
• Diazotation reactions
• Dimroth rearrangement

Dimroth
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Synthesis of Pyridazines
Carbonyl condensations
Cycloadditions
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Synthesis of Pyrimidines
Carbonyl condensations etc.
Cycloadditions
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Bioactive Pyrimidines
DNA bases
Base pairs
Double a-helix
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Anticancer comp.
Antivirals
HIV (RT -inhibitors)
Barbiturates (old sedatives)
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Synthesis of Pyrazines
Carbonyl condensations etc.
Bioactive Pyrazines/Pyridazines Pteridines
Bacteria synthezize folic acid