1. 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)

2. 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

3. Reactions with nucleophiles
Addition - Rearomatization
RMet: RLi, RMgX
[ox]: DDQ, KMnO4
1,2- add
1,4-add
Add. av NH2- (Chichibabin)

4. Substitution on halodiazines
Nucleophiles:
-ammonia / amines
-thiolates
-malonates etc.
-water / alchohols / alchoxides
Leaving groups:
-halogen
-OMe
-SO2Me
rel.
soft

5. With hard Nu:
Pd-cat. couplings

6. Metallation

7. Radical reactions (Minisci)
Cycloadditions (DA)

8. Oxydiazines Structure - Tautomerism React. with E-files
More electron rich, reacts easier with E-files than diazines
“OH” o/p directing

9. React. with Nu-files
Nu Ar subst
More complex mech.:

10. Undheim - Metaphase Inhibitors
Prophase
Anaphase
Telophase

11. N-Deprotonation / Alkylation
O-silylation / N-alkylation

12. N-Deprotonation / Alkylation
N-alkylation / C-alkylation
N-alkylation / O-alkylation

13. C-Deprotonation / Metallation
Excess base
Because of NH

14. Replacement of oxygen
Halogenation
Oxo  thio

15. Cycloadditions
Cancer
Psoralenes - Psoriasis

16. 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

17. Synthesis of Pyridazines
Carbonyl condensations
Cycloadditions

18. Synthesis of Pyrimidines
Carbonyl condensations etc.
Cycloadditions

19. Bioactive Pyrimidines
DNA bases
Base pairs
Double a-helix

20. Anticancer comp. Antivirals HIV (RT -inhibitors)
Barbiturates (old sedatives)

21. Synthesis of Pyrazines
Carbonyl condensations etc.
Bioactive Pyrazines/Pyridazines: Pteridines
Bacteria synthezize folic acid