75806-84-7

Usage

Uses

Used in Pharmaceutical Industry:
2-Bromo-3-chloro-5-(trifluoromethyl)pyridine is used as an intermediate for the synthesis of various pharmaceutical compounds. Its unique combination of functional groups allows for the development of new drugs with potential therapeutic applications.
Used in Agrochemical Industry:
2-Bromo-3-chloro-5-(trifluoromethyl)pyridine is used as an intermediate for the synthesis of agrochemicals, including pesticides and herbicides. Its pesticidal and herbicidal activities make it a valuable component in the development of new agricultural products.
Used in Synthesis of Fine Chemicals:
Due to its versatile reactivity and functionality, 2-Bromo-3-chloro-5-(trifluoromethyl)pyridine can also be used in the synthesis of other fine chemicals, further expanding its applications in various industries.

InChI:InChI=1/C7H5F7N2/c1-3-2-4(16-15-3)5(8,9)6(10,11)7(12,13)14/h2H,1H3,(H,15,16)

Synthetic route

2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → 2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7)

Conditions	Yield
With trimethylsilyl bromide at 100℃; for 15h; Inert atmosphere;	90%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7)

Conditions	Yield
With phosphorus(V) oxybromide at 150℃; for 6h; Temperature;	58%

6-hydroxy-3-pyridinecarboxylic acid (5006-66-6) → 2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen fluoride; sulfur tetrafluoride / 12 h / 100 °C / 1125.11 Torr / Autoclave 2: N-chloro-succinimide / N,N-dimethyl-formamide; 1-methyl-pyrrolidin-2-one / 8 h / 20 °C 3: phosphorus(V) oxybromide / 6 h / 150 °C View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + 2-anilineboronic acid pinacol ester (191171-55-8) → 2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]aniline (824953-11-9)

Conditions	Yield
With water; sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In dimethyl sulfoxide for 16h;	95%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + 2-(trifluoromethyl)-N-vinylbenzamide (1450903-41-9) → fluopyram (658066-35-4)

Conditions	Yield
With Cyclohexanethiol; 10-phenyl-10H-phenothiazine; sodium formate In water; dimethyl sulfoxide at 23℃; for 16h; Irradiation; Inert atmosphere; Sealed tube; Cooling; regioselective reaction;	93%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + lithium cyanide (788104-34-7, 25733-05-5) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Stage #1: 2-bromo-3-chloro-5-(trifluoromethyl)pyridine With 4-pyrrolidin-1-ylpyridine In ethanol for 6h; Reflux; Large scale; Stage #2: lithium cyanide In water; 1,2-dichloro-ethane at 80℃; for 2h; Large scale;	88.1%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + (1-(tert-butoxycarbonyl)azetidin-3-yl)zinc(II) iodide (206446-38-0) → C9H8ClF3N2

Conditions	Yield
Stage #1: 2-bromo-3-chloro-5-(trifluoromethyl)pyridine; (1-(tert-butoxycarbonyl)azetidin-3-yl)zinc(II) iodide With trifuran-2-yl-phosphane; bis(dibenzylideneacetone)-palladium(0) In tetrahydrofuran at 50℃; for 18h; Stage #2: With hydrogenchloride In methanol; water at 20℃; for 60h;	88%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + (7‐methyl‐2‐nitro‐6,7‐dihydro‐5H‐imidazo[2,1‐b][1,3]oxazin‐7‐yl)methanol (1263188-55-1) → 7-({[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-7-methyl-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 2.33333h; Inert atmosphere;	88%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + N-benzoylethyleneimine (13313-25-2) → N-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethyl)benzamide

Conditions	Yield
With Cyclohexanethiol; 10-phenyl-10H-phenothiazine; sodium formate In water; dimethyl sulfoxide at 23℃; for 16h; Irradiation; Inert atmosphere; Sealed tube; Cooling; regioselective reaction;	82%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + 4-(trifluoromethyl)-N-vinylbenzamide → N-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethyl)-4-(trifluoromethyl)benzamide (659745-39-8)

Conditions	Yield
With Cyclohexanethiol; 10-phenyl-10H-phenothiazine; sodium formate In water; dimethyl sulfoxide at 23℃; for 16h; Irradiation; Inert atmosphere; Sealed tube; Cooling; regioselective reaction;	82%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + potassium vinyltrifluoroborate → 3-chloro-5-(trifluoromethyl)-2-vinylpyridine

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In tetrahydrofuran at 80℃; for 24h; Reagent/catalyst; Temperature; Time; Solvent; Inert atmosphere;	71%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + methyl 5-cyclopropyl-2-fluoro-4-((3-methylazetidin-3-yl)methoxy)benzoate hydrochloride → methyl 4-((1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-3-methylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluorobenzoate

Conditions	Yield
With caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; bis(dibenzylideneacetone)-palladium(0) In toluene at 110℃; for 16h; Inert atmosphere; Sealed tube;	70%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + allyltributylstanane (24850-33-7) → C9H7ClF3N

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride In N,N-dimethyl-formamide at 70℃; for 3h;	67%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + 10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole (1173983-43-1) → 10-Chloro-1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole (1173978-19-2)

Conditions	Yield
With [2,2]bipyridinyl; caesium carbonate; copper(l) iodide In 1-methyl-pyrrolidin-2-one at 150℃; for 16h;	43%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + 3-(difluoromethyl)-N-(1-hydroxypropan-2-yl)-1-methyl-1H-pyrazole-4-carboxamide (1105713-22-1) → 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)-1-methyl-ethyl]amide (1105713-21-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 100℃; for 3h;	34%

N-(2-iodophenyl)-2-(trifluoromethyl)benzamide (362694-31-3) + 2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → N-{2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]phenyl}-2-(trifluoromethyl)benzamide

Conditions	Yield
Stage #1: N-(2-iodophenyl)-2-(trifluoromethyl)benzamide With potassium acetate; bis(pinacol)diborane; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In dimethyl sulfoxide at 90℃; for 2h; Stage #2: 2-bromo-3-chloro-5-(trifluoromethyl)pyridine With water; sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In dimethyl sulfoxide at 20 - 90℃; for 16h;	13%

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + copper(l) cyanide + ammonium hydroxide → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
In N-methyl-acetamide; diethyl ether

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 3-chloro-5-trifluoromethylpyridine-2-carboxylic acid (80194-68-9)

Conditions	Yield
With n-butyllithium In diethyl ether; hexane; nitrogen; water

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → C15H9Cl2F6N

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2 / water; 1,4-dioxane / 0.5 h / 20 °C / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → C15H12Cl2F3N

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2 / water; 1,4-dioxane / 0.5 h / 20 °C / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine (1512811-37-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II); XPhos / water; 1,4-dioxane / 22 h / Inert atmosphere; Heating View Scheme
Multi-step reaction with 3 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2 / water; 1,4-dioxane / 20 °C / Inert atmosphere; Heating 3: palladium diacetate; ruphos; sodium t-butanolate / 1,4-dioxane / 22 h / 20 °C / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine (1512811-37-8) + C21H18ClF3N2 (1512812-57-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; ruphos; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) / water; 1,4-dioxane / 22 h / 20 °C / Inert atmosphere; Heating View Scheme
Multi-step reaction with 3 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2 / water; 1,4-dioxane / 20 °C / Inert atmosphere; Heating 3: palladium diacetate; ruphos; sodium t-butanolate / 1,4-dioxane / 22 h / 20 °C / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 5-(2-fluorophenyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine (1512811-66-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II); XPhos / water; 1,4-dioxane / 22 h / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 1-(3-(3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepin-5-yl)phenyl)ethanone (1512811-73-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II); XPhos / water; 1,4-dioxane / 22 h / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 5-(3,5-dimethoxyphenyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine (1512811-79-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II); XPhos / water; 1,4-dioxane / 22 h / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 4-(3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepin-5-yl)benzonitrile (1512811-85-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II); XPhos / water; 1,4-dioxane / 22 h / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 7-methyl-5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine (1512811-91-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II); XPhos / water; 1,4-dioxane / 22 h / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 7-methoxy-5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine (1512811-96-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II); XPhos / water; 1,4-dioxane / 22 h / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 7-fluoro-5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine (1512812-02-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II); XPhos / water; 1,4-dioxane / 22 h / Inert atmosphere; Heating View Scheme

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) → 5-(p-tolyl)-3,8-bis(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine (1512812-07-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 2: potassium carbonate; [Rh(OH)(cod)]2; chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II); XPhos / water; 1,4-dioxane / 22 h / Inert atmosphere; Heating View Scheme

Upstream product

• 76041-71-9 3-chloro-5-(trifluoromethyl)-2-hydroxypyridine 
• 5006-66-6 6-hydroxy-3-pyridinecarboxylic acid 
• 69045-84-7 2,3-dichloro-5-trifluoromethylpyridine 

Downstream Products

• 1512811-37-8 5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1512811-79-8 5-(3,5-dimethoxyphenyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1512811-85-6 4-(3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepin-5-yl)benzonitrile 
• 1512811-91-4 7-methyl-5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1512811-96-9 7-methoxy-5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1512812-02-0 7-fluoro-5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1512812-07-5 5-(p-tolyl)-3,8-bis(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1512812-19-9 5-(3-phenylpropyl)-3,8-bis(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1512812-13-3 5-(3-phenylpropyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1512812-25-7 8-methyl-5-(3-phenylpropyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1572044-91-7 C₂₄H₂₄ClF₃N₂ 
• 1512812-43-9 5-(3,4-dimethoxybenzyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine 
• 1512812-57-5 C₂₁H₁₈ClF₃N₂ 
• 1572039-14-5 C₂₃H₂₂ClF₃N₂ 

Relevant academic research and scientific papers

A for the synthesis of anti-cancer auxiliary drug pyridine medical process for the preparation of intermediates

The invention relates to the field of medical chemistry and discloses a method for synthesizing a pyridine medical intermediate, namely 2-bromo-3-chloro-5-trifluoromethyl pyridine, for synthesizing anti-cancer auxiliary medicines. The method comprises the following steps of: (1) reacting 6-hydroxynicotinic acid, hydrofluoric acid and sulfur tetrafluoride at the temperature of between 100 and 120DEG C and under the pressure of 0.1-0.3MPa, and adding water to obtain 2-hydroxy-5-trifluoromethyl pyridine; (2) reacting with N-chlorosuccinimide, and performing water precipitation to obtain 3-chloro-5-trifluoromethyl-2-hydroxypyridine; and (3) adding excessive phosphorus oxybromide, reacting at the temperature of between 145 and 160DEG C for 5 to 8 hours, cooling, violently stirring at the temperature of between -5 and 0DEG C, extracting, combining organic phases, drying, filtering, performing spin drying, and purifying by using a silica gel column. According to the method, raw materials are readily available, the cost is low, the method is suitable for industrial production and the yield exceeds 38 percent.

Multicomponent-multicatalyst reactions (MC)2R: Efficient dibenzazepine synthesis

A RhI/Pd0 catalyst system was applied to the multicomponent synthesis of aza-dibenzazepines from vinylpyridines, arylboronic acids, and amines in a domino process with no intermediate isolation or purification.