Quinine
Title: Quinine
CAS Registry Number: 130-95-0
CAS Name: (8a,9R)-6¢-Methoxycinchonan-9-ol
Molecular Formula: C20H24N2O2
Molecular Weight: 324.42
Percent Composition: C 74.04%, H 7.46%, N 8.63%, O 9.86%
Literature References: Primary alkaloid of various species of Cinchona (Rubiaceae), see Cinchona. Representative samples of dried bark contain ~0.8 to 4% quinine. Optical isomer of quinidine, q.v. Isoln: Pelletier, Caventau, Ann. Chem. Phys. [2], 15, 291 (1820). Extraction procedure: Jucker, Stoll, in Ullmanns Encyklopädie der technischen Chemie vol. 3, 213-218 (1953). Configuration: Prelog, Zalán, Helv. Chim. Acta 27, 535 (1944); Prelog, Häfliger, ibid. 33, 2021 (1950); Roth, Pharmazie 16, 257 (1961). Synthesis: Woodward, Doering, J. Am. Chem. Soc. 66, 849 (1944); 67, 860 (1945); Taylor, Martin, ibid. 94, 6218 (1972); Gutzwiller, Uskokovic, ibid. 100, 576 (1978); G. Grethe et al., ibid. 589; T. Imanishi et al., Chem. Pharm. Bull. 30, 1925 (1982). Review of structural elucidation and early synthetic studies: R. B. Turner, R. B. Woodward in The Alkaloids vol. 3, 1-63 (1953); of bioactivity: F. E. Hahn, Ed. in Antibiotics vol. 5 (pt. 2) (Springer-Verlag, New York, 1979) pp 353-362. Comprehensive description of the hydrochloride: F. J. Muhtadi et al., Anal. Profiles Drug Subs. 12, 547-621 (1983). LC determn in soft drinks: L. P. Valenti, J. Assoc. Off. Anal. Chem. 68, 782 (1985). HPLC determn in blood: V. K. Dua et al. J. Chromatogr. 614, 87 (1993). Clinical evaluation to relieve nocturnal leg cramps: P. S. Connolly et al., Arch. Intern. Med. 152, 1877 (1992). Clinical efficacy in malaria: P. G. Kremsner et al., J. Infect. Dis. 169, 467-470 (1994). Review of historical importance and total syntheses: T. S. Kaufman, E. A. Ruveda, Angew. Chem. Int. Ed. 44, 854-885 (2005).
Properties: Triboluminescent, orthorhombic needles from abs alcohol, mp 177° (some decompn). Sublimes in high vacuum at 170-180°. [a]D15 -169° (c = 2 in 97% alcohol), [a]D17 -117° (c = 1.5 in chloroform), [a]D15 -285° (c = 0.4M in 0.1N H2SO4). pK1 (18°) 5.07; pK2 9.7. pH of satd aq soln 8.8. Absorption spectra: Dobbie, Lauder, J. Chem. Soc. 99, 1260 (1911); Dobbie, Fox, ibid. 101, 78 (1912). Fluorescence: Rabe, Marschall, Ann. 382, 362 (1911). The blue fluorescence is especially strong in dil H2SO4. One gram dissolves in 1900 ml water, 760 ml boiling water, 0.8 ml alcohol, 80 ml benzene (in 18 ml benzene at 50°), in 1.2 ml chloroform; 250 ml dry ether, 20 ml glycerol, 1900 ml of 10% ammonia water. Almost insol in petr ether.
Melting point: mp 177° (some decompn)
pKa: pK1 (18°) 5.07; pK2 9.7
Optical Rotation: [a]D15 -169° (c = 2 in 97% alcohol); [a]D17 -117° (c = 1.5 in chloroform); [a]D15 -285° (c = 0.4M in 0.1N H2SO4)
 
Derivative Type: Trihydrate
Properties: Microcrystalline powder, mp 57°, efflorescent, loses one H2O in air, two H2O over H2SO4, anhydr at 125°.
Melting point: mp 57°
 
Derivative Type: Bisulfate heptahydrate
CAS Registry Number: 6183-68-2; 549-56-4 (anhydrous)
Trademarks: Biquinate (Aventis)
Molecular Formula: C20H24N2O2.H2SO4.7H2O
Molecular Weight: 548.60
Percent Composition: C 43.79%, H 7.35%, N 5.11%, O 37.91%, S 5.84%
Properties: Very bitter crystals or cryst powder; efflorescent on exposure to air and darkens on exposure to light. One gram dissolves in 9 ml water, 0.7 ml boiling water, 23 ml alcohol, 0.7 ml alcohol at 60°, 625 ml chloroform, 2500 ml ether, 15 ml glycerol. pH: 3.5.
 
Derivative Type: Dihydrochloride
CAS Registry Number: 60-93-5
Additional Names: Quinine dichloride; quinine bimuriate; acid quinine hydrochloride
Molecular Formula: C20H24N2O2.2HCl
Molecular Weight: 397.34
Percent Composition: C 60.46%, H 6.60%, N 7.05%, O 8.05%, Cl 17.85%
Properties: Very bitter powder or crystals. One gram dissolves in about 0.6 ml water, in about 12 ml alcohol. Slightly sol in chloroform, very slightly sol in ether. Aq solns are strongly acid to litmus paper (pH about 2.6).
 
Derivative Type: Hydrochloride dihydrate
CAS Registry Number: 6119-47-7; 130-89-2 (anhydrous)
Molecular Formula: C20H24N2O2.HCl.2H2O
Molecular Weight: 396.91
Percent Composition: C 60.52%, H 7.36%, N 7.06%, O 16.12%, Cl 8.93%
Properties: Bitter, silky needles. Effloresces on exposure to warm air. Does not lose all its water below 120°. One gram dissolves in 16 ml water, in 0.5 ml boiling water, in 1.0 ml alcohol, in about 7.0 ml glycerol, in about 1 ml chloroform, in about 350 ml ether. pH (1% aq soln): 6.0-7.0. Bitterness threshold 1:30000. Protect from light.
 
Derivative Type: Sulfate dihydrate
CAS Registry Number: 6119-70-6; 804-63-7
Trademarks: Quinamm (Aventis); Quinate (Aventis)
Molecular Formula: (C20H24N2O2)2.H2SO4.2H2O
Molecular Weight: 782.94
Percent Composition: C 61.36%, H 6.95%, N 7.16%, O 20.44%, S 4.10%
Properties: Dull needles or rods, making a light and readily compressible mass. Becomes brownish on exposure to light. Loses its water of crystn at about 100°. [a]D15 -220° (5% soln in about 0.5N HCl). One gram dissolves in 810 ml water, 32 ml boiling water, 120 ml alcohol, 10 ml alcohol at 78°. Slightly sol in chloroform, ether, but freely sol in a mixture of 2 vols chloroform and 1 vol abs alcohol. Aq solns are neutral to litmus, pH of satd soln 6.2.
Optical Rotation: [a]D15 -220° (5% soln in about 0.5N HCl)
 
Use: Flavor in carbonated beverages.
Therap-Cat: Antimalarial; muscle relaxant (skeletal).
Therap-Cat-Vet: Antiprotozoal for fish.
Keywords: Antimalarial; Muscle Relaxant (Skeletal).

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