485-71-2

Basic information

• Product Name: Cinchonidine
• Synonyms: (8-alpha,9r)-cinchonan-9-o;(8alpha,9theta)-cinchonan-9-o;(8s,9r)-cinchonidine;2-Quinuclidinemethanol, alpha-4-quinolyl-5-vinyl-;Cinchonan-9-ol;Cinchonan-9-ol, (8alpha,9R)-;Cinchovatine;(-)-CINCHONIDINE
• CAS NO: 485-71-2
• Molecular Formula: C19H22N2O
• Molecular Weight: 294.39
• EINECS: 207-622-3
• Product Categories: cyclic compounds;Alkaloids;chiral;Biochemistry;for Resolution of Acids;Optical Resolution;Quinoline Alkaloids;Quinolinecarboxylic Acids, etc.;Quinolines;Synthetic Organic Chemistry;Aromatics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;AMEBARSONE
• Mol File: 485-71-2.mol
• Article Data: 17

Chemical Properties

• Melting Point: 204-206 °C(lit.)
• Boiling Point: 436.16°C (rough estimate)
• Flash Point: 234.723 °C
• Appearance: White to cream/Crystalline Powder
• Density: 1.0863 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: -107.5 ° (C=1, EtOH)
• Storage Temp.: Refrigerator
• Solubility: 0.25g/l
• PKA: 5.80, 10.03(at 25℃)
• Water Solubility: Insoluble
• Sensitive: Light Sensitive
• Stability: Stable, but light-sensitive. Incompatible with strong oxidizing agents.
• Merck: 14,2286
• BRN: 89690
• CAS DataBase Reference: Cinchonidine(CAS DataBase Reference)
• NIST Chemistry Reference: Cinchonidine(485-71-2)
• EPA Substance Registry System: Cinchonidine(485-71-2)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 20/21/22-42/43-36/37/38-20/22-48/22-43-22-63
• Safety Statements: 22-24/25-36/37-36-26
• RIDADR: 1544
• WGK Germany: 3
• RTECS: GD2975000
• TSCA: Yes
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 485-71-2(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powde

Uses

Different sources of media describe the Uses of 485-71-2 differently. You can refer to the following data:
1. antiamebic, antiprotozoal
2. Occurs in most varieties of Cinchona
3. Cinchonidine occurs in most varieties of Cinchona bark and is stereoisomeric with Cinchonine. Cinchonidine exhibits Antimalarial properties.

Definition

ChEBI: 8-epi-Cinchonan in which a hydrogen at position 9 is substituted by hydroxy (R configuration). A diasteroisomer of cinchonine, it occurs in the bark of most varieties of Cinchona shrubs, and is frequently used for directing chirality in asymmetric synthesis.

Flammability and Explosibility

Nonflammable

Purification Methods

Crystallise cinchonidine from aqueous EtOH. For the N-benzylcinchonidinium chloride see above entry in this section. [Beilstein 23 III/IV 2824.]

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-/m1/s1

Synthetic route

cinchonidine diphenylmethylsilyl ether → Cinchonidin (485-71-2)

Conditions	Yield
With potassium 4-(methoxy)phenyltrifluoroborate In dimethyl sulfoxide at 37℃; for 10h; Inert atmosphere;	64%

O-tosylcinchonidine (915134-81-5) → (Z)-1-(quinolin-4-yl)-3-((3R,4R)-3-vinylpiperidin-4-yl)prop-1-enyl 4-methylbenzene sulfonate (1393446-38-2) + (1S,3R,4S,8S,9S)-9-hydroxy-cinchonane (118-10-5, 485-70-1, 485-71-2, 550-54-9, 40134-63-2, 72402-55-2, 72402-56-3) + Cinchonidin (485-71-2)

Conditions	Yield
With salicylic acid In ethylene glycol at 95℃; for 0.25h; Microwave irradiation;	A 40% B 20% C 10%

(8S,9R)-cinchonane-9,6'-diol → Cinchonidin (485-71-2)

Conditions	Yield
ueber mehrere Stufen;

Cinchonin (118-10-5) + pentylalcoholic KOH-solution → Cinchonidin (485-71-2)

pentan-1-ol (71-41-0) + Cinchonin (118-10-5) + KOH → (1S,3R,4S,8S,9S)-9-hydroxy-cinchonane (118-10-5, 485-70-1, 485-71-2, 550-54-9, 40134-63-2, 72402-55-2, 72402-56-3) + Cinchonidin (485-71-2) + (+)-cinchonine (118-10-5, 485-70-1, 485-71-2, 550-54-9, 40134-63-2, 72402-55-2, 72402-56-3)

Conditions	Yield
Product distribution;

Cinchonin (118-10-5) → Cinchonidin (485-71-2) + epicinchonin; epicinchonidine

Conditions	Yield
With potassium hydroxide; pentan-1-ol

methyllithium (917-54-4) + Cinchonidin (485-71-2) → 2'-methylcinchonidine

Conditions	Yield
In tetrahydrofuran at -10 - 20℃; for 5h; Inert atmosphere;	100%
In tetrahydrofuran at -10 - 50℃; for 6h; Inert atmosphere; Schlenk technique;	100%
In tetrahydrofuran at -78.16℃; for 12h; Inert atmosphere;	14%
In tetrahydrofuran at -78.16℃; for 12h; Inert atmosphere;	14%

benzyl chloride (100-44-7) + Cinchonidin (485-71-2) → (8S,9R)-(-)-N-benzylcinchonidinium chloride (69221-14-3, 69257-04-1, 95189-65-4)

Conditions	Yield
In toluene for 2h; Reflux;	100%
With sodium iodide In tetrahydrofuran at 20℃; Reflux;

3,5-bistrifluoromethylphenylisothiocyanate (23165-29-9) + Cinchonidin (485-71-2) → O-((R)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)(3,5-bis(trifluoromethyl)phenyl)carbamothioate

Conditions	Yield
With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 12h; Inert atmosphere;	99%

2-{3-[(1R)-3-(3,4-dimethoxyphenyl)-1-hydroxypropyl]phenoxy}acetic acid (215169-00-9) + Cinchonidin (485-71-2) → C19H22N2O*C19H22O6

Conditions	Yield
In ethyl acetate at 50℃; for 1h;	99%

Cinchonidin (485-71-2) + methyl iodide (74-88-4) → O-methoxycinchonidine

Conditions	Yield
Stage #1: Cinchonidin 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;	98%
With sodium hydride In N,N-dimethyl-formamide at 0 - 50℃; for 2.5h;	46%
Stage #1: Cinchonidin With sodium hydride In tetrahydrofuran; mineral oil at 0 - 50℃; for 1.5h; Inert atmosphere; Schlenk technique; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 0℃; for 72h; Inert atmosphere; Schlenk technique;	1%

N2-acetyl-2,O4-dimethyltyrosine (96574-31-1) + Cinchonidin (485-71-2) → (R)-Quinolin-4-yl-((1S,2S,4S,5R)-5-vinyl-1-aza-bicyclo[2.2.2]oct-2-yl)-methanol; compound with 2-acetylamino-3-(4-methoxy-phenyl)-2-methyl-propionic acid

Conditions	Yield
	97.4%

tert-butyldimethylsilyl chloride (18162-48-6) + Cinchonidin (485-71-2) → 4-[(R)-(tert-Butyl-dimethyl-silanyloxy)-((1S,2S,4S,5R)-5-vinyl-1-aza-bicyclo[2.2.2]oct-2-yl)-methyl]-quinoline (183994-23-2)

Conditions	Yield
With dmap; triethylamine In N,N-dimethyl-formamide for 24h; Ambient temperature;	97%

Cinchonidin (485-71-2) + 4-(bromomethyl)-N-tert-butylbenzenesulfonamide (415679-05-9) → C30H38N3O3S(1+)*Br(1-)

Conditions	Yield
In methanol at 40℃; for 15h;	97%

C14H14BrNO2S + Cinchonidin (485-71-2) → C33H36N3O3S(1+)*Br(1-)

Conditions	Yield
In methanol at 40℃; for 15h;	97%

C14H14BrNO3S + Cinchonidin (485-71-2) → C33H36N3O4S(1+)*Br(1-)

Conditions	Yield
In methanol at 25℃; for 20h;	97%

Cinchonidin (485-71-2) + 1,3-bis-(bromomethyl)benzene (626-15-3) → α,α'-biscinchonidinium-m-xylene dibromide

Conditions	Yield
In ethanol; chloroform; N,N-dimethyl-formamide at 100℃; for 6h;	96%
In ethanol; chloroform; N,N-dimethyl-formamide at 100℃; for 4h;	72%
In ethanol; chloroform; N,N-dimethyl-formamide

Cinchonidin (485-71-2) + 1,3-bis-(bromomethyl)benzene (626-15-3) → C46H52N4O2(2+)*2Br(1-)

Conditions	Yield
In ethanol; chloroform; N,N-dimethyl-formamide at 100℃; for 6h;	96%

iodomethylbenzene (620-05-3) + Cinchonidin (485-71-2) → C26H29N2O(1+)*I(1-)

Conditions	Yield
In tetrahydrofuran for 12h; Inert atmosphere; Reflux;	96%

1-bromomethyl-4-nitro-benzene (100-11-8) + Cinchonidin (485-71-2) → (2S,4S,5R)-2-((R)-hydroxy(quinolin-4-yl)methyl)-1-(4-nitrobenzyl)-5-vinylquinuclidin-1-ium bromide (123355-59-9)

Conditions	Yield
In tetrahydrofuran Reflux;	95%
In acetonitrile Inert atmosphere;	83%
In tetrahydrofuran for 4h; Heating;

2-(bromomethyl)naphthalene (3163-27-7) + Cinchonidin (485-71-2) → (2S,4S,5R)-2-((R)-hydroxy(quinolin-4-yl)methyl)-1-(naphthalen-1-ylmethyl)-5-vinylquinuclidin-1-ium bromide

Conditions	Yield
In acetonitrile Inert atmosphere;	95%
In tetrahydrofuran Reflux;	80%

chloromethyldiphenylsilane (144-79-6) + Cinchonidin (485-71-2) → cinchonidine diphenylmethylsilyl ether

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;	95%

C13H11BrINO2S + Cinchonidin (485-71-2) → C32H33IN3O3S(1+)*Br(1-)

Conditions	Yield
In N,N-dimethyl-formamide at 25℃; for 20h;	94%

C11H16BrNO2S + Cinchonidin (485-71-2) → C30H38N3O3S(1+)*Br(1-)

Conditions	Yield
In N,N-dimethyl-formamide at 25℃; for 20h;	94%

C17H14BrNO2S + Cinchonidin (485-71-2) → C36H36N3O3S(1+)*Br(1-)

Conditions	Yield
In methanol at 40℃; for 18h;	94%

C14H14BrNO2S + Cinchonidin (485-71-2) → C33H36N3O3S(1+)*Br(1-)

Conditions	Yield
In N,N-dimethyl-formamide at 25℃; for 20h;	94%

Cinchonidin (485-71-2) → C19H21BrN2O

Conditions	Yield
With bromine; triethylamine In chloroform at 0 - 20℃; for 4h;	94%

4-Fluorobenzyl bromide (459-46-1) + Cinchonidin (485-71-2) → (1S,2S,4S,5R)-1-(4-Fluoro-benzyl)-2-((R)-hydroxy-quinolin-4-yl-methyl)-5-vinyl-1-azonia-bicyclo[2.2.2]octane; bromide

Conditions	Yield
In tetrahydrofuran Reflux;	93%

methanesulfonyl chloride (124-63-0) + Cinchonidin (485-71-2) → 9-O-mesyl cinchonidine

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 2h;	93%

Cinchonidin (485-71-2) → (-)-hydrocinchonidine (485-64-3)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol at 20℃; for 10h;	92%
With hydrogen; palladium on activated charcoal In methanol at 20℃; for 12h;	86%
With triethylsilane; 1% Pd on activated carbon In water at 45℃; for 24h; Reagent/catalyst; Green chemistry; chemoselective reaction;	83%

4-(bromomethyl)phenyl[di(1-naphthyl)]methanol (861815-63-6) + Cinchonidin (485-71-2) → 1-[4-{hydroxydiphenylmethyl}benzyl]cinchonidinium bromide

Conditions	Yield
In toluene; acetonitrile at 80℃; for 6h;	92%

4-(bromomethyl)-N-(phenyl)benzenesulfonamide (1308718-76-4) + Cinchonidin (485-71-2) → C32H34N3O3S(1+)*Br(1-)

Conditions	Yield
In N,N-dimethyl-formamide at 25℃; for 20h;	92%

1-(bromomethyl)-2,3,4-trifluorobenzene + Cinchonidin (485-71-2) → N-(2',3',4'-trifluoro)benzylhydrocinchonidinium bromide

Conditions	Yield
In ethanol; chloroform; N,N-dimethyl-formamide at 100℃; for 4h;	91%
In tetrahydrofuran for 4h; Heating;

5-(bromomethyl)-1,3-di-tert-butyl-2-methoxybenzene (93629-15-3) + Cinchonidin (485-71-2) → N-(4-methoxy-3,5-di-tert-butylbenzyl)cinchonidinium bromide

Conditions	Yield
In toluene for 4h; Heating;	91%

C13H9BrF3NO2S + Cinchonidin (485-71-2) → C32H31F3N3O3S(1+)*Br(1-)

Conditions	Yield
In methanol at 40℃; for 15h;	90%

4-Methylbenzyl bromide (104-81-4) + Cinchonidin (485-71-2) → (3ξ,8α,9R)-9-hydroxy-1-(4-methylbenzyl)cinchonan-1-ium bromide

Conditions	Yield
In tetrahydrofuran Reflux;	90%

Upstream product

• 118-10-5 Cinchonin 
• 71-41-0 pentan-1-ol 
• 915134-81-5 O-tosylcinchonidine 
• 560119-42-8 methanesulfonic acid (quinolin-4-yl)(5-vinyl-1-azabicyclo[2.2.2]oct-2-yl)methyl ester 
• 189309-24-8 O-tosylcinchonine 
• 560119-43-9 methanesulfonic acid (quinolin-4-yl)(5-vinyl-1-azabicyclo[2.2.2]oct-2-yl)methyl ester 
• 4363-93-3 quinoline-4-carboxaldehyde 
• 866454-14-0 C₂₆H₂₅N₃O₄ 
• 560119-43-9 C₂₀H₂₄N₂O₃S 
• 118-10-5 cinchonine 
• 560119-42-8 (8S,9R)-9-O-mesylcinchonidine 
• 118-10-5 cinchonidine 

Downstream Products

• 60210-91-5 L-2-(2,3,4,6-tetrachloro-phenoxy)-propionic acid 
• 69-24-9 cinchonicine 
• 772-14-5 (R)-3-phenylbutyric acid 
• 4286-15-1 (S)-2-phenylbutyric acid 
• 938-79-4 (2R)-2-phenylbutanoic acid 
• 3205-38-7 (S)-trans-1.2-bis-carboxymethyl-cyclohexane 
• 62057-34-5 (R)-trans-1.2-bis-carboxymethyl-cyclohexane 
• 127413-52-9 (S)-3-benzamido-3-phenylpropanoic acid 
• 60210-90-4 D-2-(2,3,4,6-tetrachloro-phenoxy)-propionic acid 
• 14402-56-3 (8S,9R)-9-Benzoyloxy-cinchonan 
• 73771-80-9 (2S,4S,5R)-1-ethyl-2-((R)-hydroxy(quinolin-4-yl)methyl)-5-vinylquinuclidin-1-ium iodide 
• 73804-27-0 (8S,9R)-9-hydroxy-1-methyl-cinchonanium; iodide 
• 14509-68-3 cinchonan-9-one 
• 490-11-9 3,4-pyridinecarboxylic acid 

Relevant articles and documents

Exploration of the Fluoride Reactivity of Aryltrifluoroborate on Selective Cleavage of Diphenylmethylsilyl Groups

The first known report on the fluoride catalytic reactivity of potassium aryltrifluoroborate is described. The fluoride reactivity of phenyltrifluoroborate was controlled by substituents on the trifluoroborate-attached benzene, such as the methoxy group a

An easy route to exotic 9-epimers of 9-amino-(9-deoxy) cinchona alkaloids with (8S, 9R) and (8R, 9S)-configurations through two inversions of configuration

Four exotic chiral organocatalysts, 9-amino-(9-deoxy) cinchona alkaloids with (8S, 9R) and (8R, 9S)-configurations, were conveniently synthesized for the first time in 27-72% total yields through two conversions of configuration at the 9-stereogenic centers of commercially available cinchona alkaloids.

Structure-reactivity study of O-tosyl Cinchona alkaloids in their new synthesis and in hydrolysis to 9-epibases. Unexpected formation of cinchonicine enol tosylate accelerated by microwave activation

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.