Wheel of Diazotization Reactions

Leverage the power of diazotization!


The diazotization (aka diazonium salt formation reaction, or diazoniation, or diazotation, or Griess diazo reaction) is synthetically versatile as the salt can react with a variety of nucleophiles. These reactions take place by the aromatic nucleophilic substitution unimolecular mechanism (NAS, SN1Ar or SRN1).

During diazotization of primary arylamines, an excess of mineral acid is used as the acid prevents the coupling of the diazonium salt formed with the arylamine by converting the arylamine to its salt (deactivation of the p-position of the arylamine).


My fun fact 😊 about the azo dye: When I was doing my B. Pharm., I remember one of my labmates saying like, "Let him keep stirring it and finish the reaction so that we can go to the canteen to have some snacks and tea." as I was the one who was consistently using the stirring rod to facilitate the 'slow' reaction.



Wheel of diazotization reactions: Click/tap to enlarge the image


Reagents -> Products (on the infographic):

  1. Hypophosphorous acid or Sodium borohydride (or Absolute Ethanol (EtOH), Δ or Sodium stannite (Na2SnO2), Δ) -> Benzene (or Aniline (PhNH2) depending on the reducing agent)
  2. Deuterium oxide or Deuterated alcohol, pH > 7 -> Mono-deuterated benzene
  3. Fluoroboric acid, Δ (Balz-Schiemann reaction or Schiemann reaction) -> Fluorobenzene
  4. Copper(I) chloride, Δ (Sandmeyer reaction) or Copper, Hydrogen chloride, Δ (Gattermann reaction) -> Chlorobenzene
  5. Copper(I) bromide, Δ (Sandmeyer reaction) or Copper, Hydrogen bromide, Δ (Gattermann reaction) -> Bromobenzene
  6. Potassium iodide, Δ -> Iodobenzene
  7. Sulfuric acid, Water, Δ -> Phenol
  8. Alcohols, pH < 1 -> Alkyl phenyl ethers (aromatic ethers)
  9. Potassium alkyl xanthates, Potassium hydroxide -> Thiophenols
  10. Sodium salt of aryl mercaptans -> Aryl phenyl sulfides
  11. Potassium thiocyanate -> Phenyl thiocyanate
  12. Sodium azide -> Phenyl azide
  13. Sodium nitrite, Copper -> Nitrobenzene
  14. Trifluoromethyltrimethylsilane (Ruppert-Prakash reagent), Copper -> Benzotrifluoride
  15. Copper(I) cyanide, Δ (Sandmeyer reaction) or Copper, Potassium cyanide (Potassium copper(I) cyanide), Δ (Gattermann reaction) -> Benzonitrile
  16. Arenes, Sodium hydroxide -> Aryl benzenes

 

Reagents -> Products (NOT on the infographic):

 

17. Aniline (in mildly acidic solution) (azo coupling or diazo coupling) -> 4-(Phenyldiazenyl)aniline (PhN=NC6H4NH2, an azo dye called aniline yellow)

NOTE: A highly acidic solution (low pH) prevents the coupling of the diazonium salt with the arylamine by converting the arylamine to its non-nucleophilic salt (deactivation of the p-position of the arylamine). A highly basic solution (high pH) gives ArN=NOH (diazohydroxide) and ArN=NO- (diazotate anion) neither of which couples (non-electrophilic).

18. 2-Naphthol (in mildly basic solution) (azo coupling) -> 1-(Phenyldiazenyl)naphthalen-2-ol (C16H12N2O, an azo dye called Sudan I)

NOTE: A strongly acidic medium suppresses the ionization of the phenolic moiety to its more reactive conjugate base. A strongly basic medium gives ArN=NOH and ArN=NO- neither of which couples.

19. i. Sodium sulfite (Na2SO3), Hydrochloric acid (HCl), Δ ii. Sodium hydroxide (or Tin(II) chloride (SnCl2), HCl) -> Phenylhydrazine (PhNHNH2)

 

& others

 

When the coupling partners in 17/18 are arenes, viz., anilines and phenols, it's an EAS (electrophilic aromatic substitution).


What other wheel(s) 🎡 of organic reactions would you like to see❓ Questions❓ Let Chemaficionado know in the comments below or at mychemistryhomework@gmail.com❗


References:

(1)    Valiulin, R. Organic Chemistry: 100 Must-Know Mechanisms; De Gruyter: Berlin, 2023.

(2)    Diazonium compound. Wikipedia. https://en.wikipedia.org/wiki/Diazonium_compound.‌

(3)    Phenylhydrazine. Wikipedia. https://en.wikipedia.org/wiki/Phenylhydrazine.

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