Diazines such as pyridine, pyrimidine, and pyrazine react less readily with electrophiles than pyridine but more easily with nucleophiles through additions and substitutions. They also undergo radical reactions and diene additions. Oxydiazines contain an oxygen atom, making them more electron-rich and able to react more easily with electrophiles than diazines. Aminodiazines contain amino groups that act as electron donors, allowing them to participate more readily in electrophilic aromatic substitutions. Several important bioactive compounds contain diazine rings, including DNA bases, anticancer drugs, HIV inhibitors, and pteridines.

1. DIAZINES
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)
Only C-5 in pyrimidine
NOT elctron def.

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. Pd-cat. couplings
With hard Nu:

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 Metaphase 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
Cycloadditions
Carbonyl condensations

18. Synthesis of Pyrimidines
Carbonyl condensations etc.
Cycloadditions

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

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