118-10-5

Basic information

• Product Name: Cinchonine
• Synonyms: D-CINCHONINE;(+)-CINCHONINE;CINCHONINE;CINCHONAN-9-OL,(9S)-;(+)-cinconine;(8r,9s)-cinchonine;(9s)-cinchonan-9-o;(9S)-Cinchonan-9-ol
• CAS NO: 118-10-5
• Molecular Formula: C₁₉H₂₂N₂O
• Molecular Weight: 294.39
• EINECS: 204-234-6
• Product Categories: Miscellaneous Natural Products;chiral;Alkaloids;Biochemistry;for Resolution of Acids;Optical Resolution;Quinoline Alkaloids;Quinolinecarboxylic Acids, etc.;Quinolines;Synthetic Organic Chemistry;Asymmetric Synthesis;Chiral Resolution Reagents;Chiral Resolving ReagentsChiral Catalysts, Ligands, and Reagents;Cinchona Alkaloids;Privileged Ligands and Complexes;Aromatics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;API;DOBUTREX
• Mol File: 118-10-5.mol
• Article Data: 16

Chemical Properties

• Melting Point: 260-263 °C
• Boiling Point: 436.16°C (rough estimate)
• Flash Point: 234.7 °C
• Appearance: White to light beige/Micro-Crystalline Powder
• Density: 1.0863 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 223 ° (C=0.5, EtOH)
• Storage Temp.: Store below +30°C.
• Solubility: 0.25g/l
• PKA: 5.85, 9.92(at 25℃)
• Water Solubility: Insoluble
• Sensitive: Light Sensitive
• Stability: Stable, but may be light sensitive. Incompatible with strong oxidizing agents.
• Merck: 14,2287
• BRN: 89689
• CAS DataBase Reference: Cinchonine(CAS DataBase Reference)
• NIST Chemistry Reference: Cinchonine(118-10-5)
• EPA Substance Registry System: Cinchonine(118-10-5)

Safety Data

• Hazard Codes: Xn
• Statements: 20/22-20/21/22
• Safety Statements: 26-36-36/37
• RIDADR: 1544
• WGK Germany: 3
• RTECS: GD3500000
• F: 8-34
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 118-10-5(Hazardous Substances Data)

Usage

Description

Cinchonine is a cinchona alkaloid generally found in the bark of Cinchona officinalis plants. It is a pseudoenantiomer that is commonly employed in malaria therapy. Cinchonine is also used as an organocatalyst in many asymmetric reactions. It is a stereoisomer and pseudo-enantiomer of cinchonidine. It is structurally similar to quinine, an antimalarial drug.

Chemical Properties

white to light yellow crystal powde

Uses

Different sources of media describe the Uses of 118-10-5 differently. You can refer to the following data:
1. cardiotonic
2. Stereomeric with Cinchonidine (C441925). Antimalarial.
3. Cinchonine occurs in most varieties of cinchonabark (Cinchona micrantha and Rubiaceae).It is used as an antimalarial agent.

Definition

ChEBI: Cinchonan in which a hydrogen at position 9 is substituted by hydroxy (S configuration). It occurs in the bark of most varieties of Cinchona shrubs, and is frequently used for directing chirality in asymmetric synthesis.

Health Hazard

The toxic effects from high doses of cinchonineinclude tinnitus, vomiting, diarrhea, andfever. The toxic effects noted in rats were excitement, change in motor activity, andconvulsions. An intraperitoneal LD50 valuein rats is 152 mg/kg.

Flammability and Explosibility

Nonflammable

Purification Methods

Crystallise cinchonine from EtOH or diethyl ether. For the N-benzylcinchoninium chloride see above entry in this section. [Rabe Justus Liebigs Ann Chem 365 366, 371 1909, Beilstein 23 III/IV 2819, 2832.]

InChI:InChI=1/C19H22N2O/c1-2-13-12-21-10-8-14(13)11-18(21)19(22)16-7-9-20-17-6-4-3-5-15(16)17/h2-7,9,13-14,18-19,22H,1,8,10-12H2/p+1/t13-,14-,18+,19-/m0/s1

Synthetic route

O-tosylcinchonine (189309-24-8) → (Z)-1-(quinolin-4-yl)-3-((3R,4R)-3-vinylpiperidin-4-yl)prop-1-enyl 4-methylbenzene sulfonate (1393446-38-2) + Cinchonin (118-10-5) + (+)-cinchonine (118-10-5, 485-70-1, 485-71-2, 550-54-9, 40134-63-2, 72402-55-2, 72402-56-3)

Conditions	Yield
With salicylic acid In ethylene glycol at 95℃; for 0.5h; Microwave irradiation;	A 60% B 15% C 15%

methanesulfonic acid (quinolin-4-yl)(5-vinyl-1-azabicyclo[2.2.2]oct-2-yl)methyl ester (560119-43-9) → Cinchonin (118-10-5) + (+)-cinchonine (118-10-5, 485-70-1, 485-71-2, 550-54-9, 40134-63-2, 72402-55-2, 72402-56-3) + (1S,2R,3S,5S,6R)-2-(quinolin-4-yl)-6-vinyl-1-azabicyclo[3.2.2]nonan-3-ol (560119-45-1) + (E)-cinchene

Conditions	Yield
With water; tartaric acid at 100℃; Title compound not separated from byproducts;	A n/a B n/a C 48% D 1%

cinchonan-9-one (14509-68-3, 14528-54-2, 72402-48-3, 72402-49-4) + acetic acid (64-19-7) + iron powder → Cinchonin (118-10-5)

cinchonan-9-one (14509-68-3, 14528-54-2, 72402-48-3, 72402-49-4) + ethanol (64-17-5) + sodium → Cinchonin (118-10-5)

benzoylcinchonine (14402-57-4) + alcoholic KOH-solution → benzoic acid (65-85-0) + Cinchonin (118-10-5)

Conditions	Yield
at 60 - 70℃;

(9S,10Ξ)-10-iodo-10,11-dihydro-cinchonan-9-ol; dihydriodide hydrate + water → Cinchonin (118-10-5) + 9,10-Epoxy-10,11-dihydro-cinchonan (7299-23-2) + apocinchonine

Conditions	Yield
at 150 - 160℃; im Rohr; isomer(ic) I;

Cinchonin (118-10-5) + Tert-butyl isocyanate (1609-86-5) → (9S)-9-deoxy-cinchonin-9-yl tert-butylcarbamate

Conditions	Yield
With dibutyltin(II) dilaurate In toluene at 110℃; for 48h;	99%

methyllithium (917-54-4) + Cinchonin (118-10-5) → 2'-methylcinchonine

Conditions	Yield
In tetrahydrofuran at -10 - 50℃; for 6h; Inert atmosphere; Schlenk technique;	99%
In tetrahydrofuran at -78.16℃; for 12h; Inert atmosphere;

anthracenylmethyl chloride (24463-19-2) + Cinchonin (118-10-5) → (2R,5R,1'S)-1-(9-anthracenyl)methyl-5-ethylene-2-[1-hydroxy-1-(quinol-4-yl)]methyl-1-azoniabicyclo[2.2.2]octane chloride

Conditions	Yield
In toluene at 110℃; for 2h;	98%
In toluene Reflux;	94%
In toluene for 24h; Heating;	80%

(1E,4E)-1,5-bis(4-(bromomethyl)phenyl)penta-1,4-dien-3-one + Cinchonin (118-10-5) → C57H60N4O3(2+)*2Br(1-)

Conditions	Yield
In tetrahydrofuran; N,N-dimethyl-formamide Reflux;	98%

5,5'-bis(bromomethyl)-2,2'-bipyridine (92642-09-6) + Cinchonin (118-10-5) → C50H54N6O2(2+)*2Br(1-)

Conditions	Yield
In tetrahydrofuran Reflux;	96%

benzyl chloride (100-44-7) + Cinchonin (118-10-5) → (9S)-9-hydroxy-1-(phenylmethyl)-cinchonanium chloride (69221-14-3)

Conditions	Yield
In ethanol; chloroform; N,N-dimethyl-formamide at 100℃; for 10h;	95%
With ethanol
In N,N-dimethyl-formamide at 80℃; for 3h; N-quaternization;

(1E)-1,2-bis[3-(bromomethyl)phenyl]diazene (60682-97-5, 66888-72-0, 29477-66-5) + Cinchonin (118-10-5) → C54H58N4O2(2+)*2Br(1-)

Conditions	Yield
In tetrahydrofuran; acetonitrile Reflux;	95%

p-toluenesulfonyl chloride (98-59-9) + Cinchonin (118-10-5) → O-tosylcinchonine (189309-24-8)

Conditions	Yield
Stage #1: Cinchonin With sodium hydride In tetrahydrofuran at 70℃; for 2h; deprotonation; Stage #2: p-toluenesulfonyl chloride In tetrahydrofuran at 60 - 70℃; for 10h; Tosylation;	94%
With tributyl-amine; potassium hydroxide In dichloromethane; water at 20℃; for 24h;	90%
With pyridine

Cinchonin (118-10-5) → dihydrocinchonine (485-65-4)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 10h;	92%
With sulfuric acid; palladium Hydrogenation;
With palladium; acetic acid Hydrogenation;

Cinchonin (118-10-5) + methyl iodide (74-88-4) → (1S,4S,5R)-2-((S)-methoxy(quinolin-4-yl)methyl)-5-vinylquinuclidine

Conditions	Yield
Stage #1: Cinchonin With potassium hydride In N,N-dimethyl-formamide; mineral oil; pentane at 0 - 50℃; for 3h; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil; pentane at 0 - 20℃; Inert atmosphere;	91%
Stage #1: Cinchonin With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil at 20℃;	60%
Stage #1: Cinchonin With potassium hydride In tetrahydrofuran; mineral oil at 0 - 50℃; for 3h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere;	59%

p-(chloromethyl)benzoyl chloride (876-08-4) + Cinchonin (118-10-5) → C27H27ClN2O2

Conditions	Yield
With triethylamine In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 20℃; under 760.051 Torr; for 16h;	90%

methanesulfonyl chloride (124-63-0) + Cinchonin (118-10-5) → methanesulfonic acid (quinolin-4-yl)(5-vinyl-1-azabicyclo[2.2.2]oct-2-yl)methyl ester (560119-43-9)

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃;	88%

4-chlorobenzyl bromide (622-95-7) + Cinchonin (118-10-5) → N-(4-chlorobenzyl)cinchoninium bromide

Conditions	Yield
In tetrahydrofuran for 5.5h; Reflux;	87.8%
In tetrahydrofuran for 84h; Heating;	52%

benzyl chloride (100-44-7) + Cinchonin (118-10-5) → O-benzylcinchonine (1261665-86-4)

Conditions	Yield
Stage #1: Cinchonin With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Stage #2: benzyl chloride In N,N-dimethyl-formamide; mineral oil	87%
Stage #1: Cinchonin With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Stage #2: benzyl chloride In N,N-dimethyl-formamide; mineral oil	86%

allyl bromide (106-95-6) + Cinchonin (118-10-5) → O-allylcinchonine (852951-76-9)

Conditions	Yield
Stage #1: Cinchonin With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Stage #2: allyl bromide In N,N-dimethyl-formamide; mineral oil	87%
Stage #1: Cinchonin With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Stage #2: allyl bromide In N,N-dimethyl-formamide; mineral oil	87%
Stage #1: Cinchonin With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Stage #2: allyl bromide In N,N-dimethyl-formamide; mineral oil at 20℃;	87%
With sodium hydride In N,N-dimethyl-formamide at 30℃; for 2h;	87%

benzyl bromide (100-39-0) + Cinchonin (118-10-5) → (1S,2R,4S,5R)-1-benzyl-2-((S)-(1-benzylquinolin-1-ium-4-yl)(hydroxy)methyl)-5-vinylquinuclidin-1-ium bromide

Conditions	Yield
In N,N-dimethyl-formamide; isopropyl alcohol at 70℃; for 12h; Inert atmosphere;	87%

4,6-dichloro-2,5-diphenylpyrimidine (29133-99-1) + Cinchonin (118-10-5) → C35H31ClN4O

Conditions	Yield
With potassium hydroxide In toluene for 1h; Inert atmosphere; Reflux;	87%

benzyl bromide (100-39-0) + Cinchonin (118-10-5) → (+)-N-benzylcinchonineammonium bromide (85653-34-5)

Conditions	Yield
In tetrahydrofuran for 4.5h; Reflux;	86.9%
In tetrahydrofuran for 16h; Reflux;	82%
In acetonitrile at 20℃; for 24h; Inert atmosphere;

C27H31Br + Cinchonin (118-10-5) → C46H53N2O(1+)*Br(1-)

Conditions	Yield
In tetrahydrofuran for 16h; Reflux;	86%

3,5-bis(trifluoromethyl)benzyl bromide (32247-96-4) + Cinchonin (118-10-5) → N1-3,5-bis(trifluoromethyl)benzylcinchonium bromide

Conditions	Yield
In tetrahydrofuran for 12h; Heating;	85%
In tetrahydrofuran for 24h; Reflux;	79%
In toluene at 80℃; Inert atmosphere;	72%

succinic acid anhydride (108-30-5) + Cinchonin (118-10-5) → C23H26N2O4

Conditions	Yield
With dmap In dichloromethane at 50℃;	84%

2-bromomethylnaphthyl bromide (939-26-4) + Cinchonin (118-10-5) → N-(2-napthylmethyl)cinchoninium bromide (207561-98-6)

Conditions	Yield
In tetrahydrofuran for 16h; Reflux;	83%

2-Iodobenzyl bromide (40400-13-3) + Cinchonin (118-10-5) → N-2-iodobenzylcinchoninium bromide (1410875-87-4)

Conditions	Yield
In tetrahydrofuran for 12h; Reflux; Inert atmosphere;	82%

1-bromomethyl-2-chlorobenzene (611-17-6) + Cinchonin (118-10-5) → N-(2-chlorobenzyl)cinchoninium bromide (1261665-70-6)

Conditions	Yield
In tetrahydrofuran for 6h; Reflux;	81.2%

Cinchonin (118-10-5) → (8R,9R)-9-amino(9-deoxy)epicinchonin

Conditions	Yield
Stage #1: Cinchonin With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃; for 0.25h; Inert atmosphere; Stage #2: With diphenylphosphoranyl azide In tetrahydrofuran at 0 - 50℃; Inert atmosphere; Stage #3: With hydrogenchloride In dichloromethane; water	81%
Stage #1: Cinchonin With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: With ammonia In tetrahydrofuran; chloroform at 0 - 60℃;	78%
Multi-step reaction with 2 steps 1.1: diphenyl phosphoryl azide; triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran / 0 - 50 °C 2.1: triphenylphosphine / 15 h / 50 °C 2.2: 24 h / 20 °C View Scheme

9,1-bis(chloromethyl)anthracene (10387-13-0) + Cinchonin (118-10-5) → C54H56N4O2(2+)*2Cl(1-)

Conditions	Yield
In ethanol; chloroform; N,N-dimethyl-formamide at 100℃;	80%

9-bromoethylanthracene (2417-77-8) + Cinchonin (118-10-5) → N-(anthracen-9-ylmethyl)cinchoninium bromide (365567-24-4)

Conditions	Yield
In tetrahydrofuran for 4.5h; Reflux;	79.6%
In tetrahydrofuran for 8h; Inert atmosphere; Reflux;	71%
In tetrahydrofuran for 16h; Reflux;	52%

p-Methoxybenzyl bromide (2746-25-0) + Cinchonin (118-10-5) → N-(4-methoxybenzyl)cinchoninium bromide (207561-99-7)

Conditions	Yield
In tetrahydrofuran for 3.5h; Reflux;	78.6%

1-bromomethyl-4-bromobenzene (589-15-1) + Cinchonin (118-10-5) → N-(p-bromobenzyl)-cinchoninium bromide

Conditions	Yield
In chloroform 1.) reflux, 40 min, 2.) room temperature, 19 h;	77%
In tetrahydrofuran for 5.5h; Reflux;	66.3%
In tetrahydrofuran for 44h; Heating;	41%

3-phenylprop-2-en-1-yl bromide (4392-24-9) + Cinchonin (118-10-5) → N-cinnamyl-cinchoninium bromide

Conditions	Yield
In chloroform 1.) reflux, 2.) room temperature;	77%

Upstream product

• 14402-57-4 benzoylcinchonine 
• 560119-43-9 C₂₀H₂₄N₂O₃S 
• 118-10-5 cinchonine 
• 866454-14-0 C₂₆H₂₅N₃O₄ 
• 560119-42-8 (8S,9R)-9-O-mesylcinchonidine 
• 118-10-5 cinchonidine 
• 189309-24-8 O-tosylcinchonine 
• 4363-93-3 quinoline-4-carboxaldehyde 
• 560119-43-9 methanesulfonic acid (quinolin-4-yl)(5-vinyl-1-azabicyclo[2.2.2]oct-2-yl)methyl ester 

Downstream Products

• 118-10-5 10,11-dihydrocinchonidine 
• 118-10-5 C⁽⁹⁾-epi-cinchonidine 
• 69-24-9 cinchonicine 
• 485-71-2 Cinchonidin 
• 118-10-5 (1S,3R,4S,8S,9S)-9-hydroxy-cinchonane 
• 118-10-5 (+)-cinchonine 
• 486-74-8 4-quinolinic acid 
• 53913-66-9 cinchotenine 
• 64-18-6 formic acid 
• 82260-55-7 (3R,4S)-1-<2-(4-benzyloxy-3-methyloxyphenyl)-2-hydroxyethyl>-3-ethyl-4-piperidineacetic acid ethyl ester 
• 82260-54-6 (3R,4S)-(+)-1-(4-benzyloxy-3-methoxyphenacyl)-3-ethyl-4-piperidineacetic acid ethyl ester 

Related news

Solvent effect on absorption and fluorescence spectra of Cinchonine (cas 118-10-5) and cinchonidine dications: Estimation of ground and excited state dipole moments by experimental and numerical studies08/30/2019

Absorption and fluorescence spectra of dications of cinchonine (C2 +) and cinchonidine (Cd2 +) have been measured at room temperature in solvents of different polarities. Ground and excited state electric dipole moments are determined experimentally using solvatochromic shift method based on bul...detailed

Polymer microenvironmental effects on the photophysics of Cinchonine (cas 118-10-5) dication08/28/2019

Photophysical properties of cinchonine dication (C++) have been studied in protic and aprotic polymers by monitoring steady state and time resolved measurements. It is found to be sensitive towards the microenvironment of polymers. Edge excitation red shifted emission (EERS) is observed in all p...detailed

ArticleChitosan-supported Cinchonine (cas 118-10-5) as an efficient organocatalyst for direct asymmetric aldol reaction in water08/26/2019

Chitosan-supported succinic anhydride-cinchonine (CTS-SA-CN) was synthesized via a two-step route with succinic anhydride as the linker. The catalyst was used to promote the direct asymmetric aldol reaction between cyclohexanone and a variety of aromatic aldehydes in aqueous medium. Aldol adduct...detailed

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New methods for O-tosylation of the natural Cinchona alkaloids have been discovered as a biphasic processes with Bu3N as a catalyst. The optimized excess of tosyl chloride, necessary for transformation of each of the four alkaloids into O-tosyl derivative, decreases in the following order: quinine, quinidine, cinchonidine and cinchonine. The same decreasing order has been noticed for the hydrolysis rate of the appropriate tosylates to 9-epibases. Difficult conversion of O-tosylcinchonine in the hydrolytic medium of aqueous tartaric acid gives 9-epicinchonine together with parallel formation of cinchonicine enol tosylate. The latter product is obtained as the main when both cinchonine and cinchonidine tosylates react in the presence of salicylic acid under controlled microwave heating. On the basis of X-ray structure of the new alkene product, the stereoselective syn-E2 quinuclidine ring opening process, competing to the SN2 hydrolysis is postulated for this transformation. ARKAT-USA, Inc.