Chapter 16. Quinoline and isoquinoline derivatives

QUINOLINE DERIVATIVES

Cinchonan

Quinine hydrochloride Chinini hydrochloridum 9-oxy-6-metoxy-cinchonanhydro-chloride	Quinine sulfate Chinini sulfas 9-oxy-6-metoxy-cinchonan sulfate
Structure Quinine base is a cinchonan dericative, quinoline core, secondary aliphatic hydroxy group, substituted phenolic hydroxyl, quinuclidine (2 piperidine cycles), vinyl radical.
Substance is a salt of quinine base with hydrochloric acid (bond formed with quinuclidine nitrogenas the most active basic centre). White fine crystal powder, odorless, soluble in water.	Substance is a salt of quinine base with sulfuric acid (bond formed with quinuclidine nitrogen as the most active basic centre). White fine crystal powder, odorless, slightly soluble in water. Emits blue fluorescence under UV-light.

Identification

1. Melting temperature, UV and IR spectroscopy.
2. Tests.
   • Proof of salt: water solubility. Hydrochloride is soluble, sulfate is slightly soluble. pH is acidic, quinine base can be precipitated by sodium hydroxide or ammonia solution.
   • Basic properties: alkaloid precipitating reagents.
   • Group reaction: Thalleoquin's test (based on methoxy group). Bromine water and ammonia are added to aqueous solution of quinine salt, a green coloration is observed.

• Herapathite formation: spiritous solution of iodine is added to quinine solution in sulfuric acid, formation of dark-green crystals is observed.
• Erythroquine test: bromine water and alkaline solution of potassium hexacyanoferrate (III) are added to substance solution. Erythroquine formation is observed (red coloration).

• Distinguishing between substances: watersolubility, fluorescence, chloride- and sulfate-ions reactions.

Assay

• Quinine hydrochloride ― acid-base titration of quinuclidine and quinoline nitrogen.

• Quinine sulfate ― acid-base titration.

• Spectrophotometry, HPLC.

8-oxyquinoline derivatives

Nitroxoline

Nitroxolinum

5-nitro-8-oxyquinoline

Description: Fine yellow-green crystal powder; practically in soluble in water.

Identification

Melting temperature, UV and IR spectroscopy

Tests

1. Ampholyte ― acidic phenol hydroxyl and basic nitrogen.
2. All phenol hydroxyl reactions (see Phenols).
3. Chelate complex formation with magnesium salts.
4. Azo dye formation: can be performed with phenol hydroxyl or aromatic nitro group after reducing it to primary aromatic amino group.

Assay

Non-aqueous acid-base titration as acid. Solvent ― dimethylformamide, titrant ― spiritous solution of sodium hydroxide or alkali metal alcoholates (end product ― phenolate).

4-quinolone derivatives

Ciprofloxacin

Ciprofloxacinum

Description: White crystal powder, odorless, soluble in water.

Identification:

1. melting temperature, UV and IR spectroscopy;
2. organic fluorine ― mineralized by burning in oxygen flask:

a) with calcium salts ― white precipitate

Ca²⁺ + 2F^-= CaF₂↓;

b) discoloration of red iron thiocyanate solution;

c) reaction with zirconium-alizarin indicator;

3. dark-red chelate complex formation (with iron (III) chloride):

Assay

UV spectrophotometry, HPLC.

ISOQUINOLINE DERIVATIVES

Benzylisoquinoline derivatives

Papaverine hydrochloride

Papaverini hydrochloridum

Substance is a salt of a benzyl isoquinoline derivative containing 4 methoxy groups.

Description: white crystalline powder, odorless, sparingly soluble in water.

Identification

Melting temperature, UV and IR spectroscopy.

• Proof of ionic bond salt (water solubility, acidic pH, papaverine is a very weak base , therefore it is precipitated not only by ammonia and sodium hydroxide, but also with a solution of sodium acetate) precipitation with sodium acetate, as well as ammonia and sodium hydroxide).
• Proof of basic properties: general alkaloid reagents (formation of precipitates).
• Proof of methoxy groups (substituted phenol hydroxyls).
• Oxidation reactions. Formation of colored products: purple with concentrated sulfuric acid, yellow with concentrated nitric acid, Erdmann reagent, Marquis reagent, etc.

Assay

Non-aqueous acid-base titration. Solvent ― concentrated acetic acid with mercury acetate or acetic anhydride for binding of chloride-ion. Titrant ― HClO₄.

Phenanthrene isoquinoline derivatives

Morphine hydrochloride

Morphini hydrochloridum

Substance is a partially hydrated phenanthrene (A, B, C), hydrated isoquinoline (C, D), piperidine (D), salt of hydrochloric acid, has phenolic and aliphatic hydroxy groups.

Description: White crystalline powder, slightly soluble in water.

Codeine Codeinun	Codeine phosphate Codeini phosphas
White crystalline powder, slightly soluble in water, strong base.	White crystalline powder, freely soluble in water.