50488-42-1

Basic information

• Product Name: 2-Bromo-5-(trifluoromethyl)pyridine
• Synonyms: 2-BROMO-5-(TRIFLUOROMETHYL)PYRIDINE;6-BROMO-3-TRIFLUOROMETHYLPYRIDINE;BUTTPARK 27\06-86;2-bromo-5-(trifluoromethyl)pyr;2-Bromo-5-(trifluoromethyl)pyridine 97%;2-Bromo-5-(trifluoromethyl)pyridine97%;2-bromo-5-(trifuorometnyl)pyridine;2-Bromo-5-(trifluomethyl)pyridine
• CAS NO: 50488-42-1
• Molecular Formula: C₆H₃BrF₃N
• Molecular Weight: 225.99
• EINECS: 2017-001-1
• Product Categories: Pyridine;Pyridine series;Halides;Pyridines;C6Heterocyclic Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Building Blocks;C5 to C6;C6 to C7;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks;Fluorine series
• Mol File: 50488-42-1.mol
• Article Data: 2

Chemical Properties

• Melting Point: 44-48 °C
• Boiling Point: 78 °C
• Flash Point: 78-81°C/30mm
• Appearance: /Crystalline
• Density: 1.707 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.572
• Storage Temp.: Room temperature.
• Solubility: Soluble in methanol and ethanol.
• PKA: -1?+-.0.10(Predicted)
• CAS DataBase Reference: 2-Bromo-5-(trifluoromethyl)pyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Bromo-5-(trifluoromethyl)pyridine(50488-42-1)
• EPA Substance Registry System: 2-Bromo-5-(trifluoromethyl)pyridine(50488-42-1)

Safety Data

• Hazard Codes: T,Xi,Xn
• Statements: 25-36/37/38-20/21/22
• Safety Statements: 26-36/37/39-22-36
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• HazardClass: IRRITANT
• PackingGroup: Ⅲ
• Hazardous Substances Data: 50488-42-1(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow needles

Uses

Different sources of media describe the Uses of 50488-42-1 differently. You can refer to the following data:
1. 2-Bromo-5-(trifluoromethyl)pyridine is substrate used in a palladium-catalyzed α-arylation of a Refomatsky reagent.
2. 2-Bromo-5-(trifluoromethyl)pyridine is a substrate used in a palladium-catalyzed α-arylation of a Refomatsky reagent.

InChI:InChI=1/C13H8F2O2/c14-11-6-5-10(7-12(11)15)8-1-3-9(4-2-8)13(16)17/h1-7H,(H,16,17)

Synthetic route

2-chloro-5-trifluoromethylpyridine (52334-81-3) → 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1)

Conditions	Yield
With trimethylsilyl bromide In various solvent(s) for 20h; Heating;	76%

2-bromo-5-iodo-pyridine (73290-22-9) + (trifluoromethyl)trimethylsilane (81290-20-2) → 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1)

Conditions	Yield
With potassium fluoride; copper(l) iodide In 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide at 25℃; for 6h;	29%

2,5-dibromopyridine (624-28-2) → 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: nBuLi / hexane; diethyl ether / 0.75 h / -75 °C 1.2: 84 percent / I2 / hexane; tetrahydrofuran; diethyl ether / 0.75 h / -75 °C 2.1: 29 percent / KF; CuI / dimethylformamide; 1-methyl-pyrrolidin-2-one / 6 h / 25 °C View Scheme

methanol (67-56-1) + carbon monoxide (201230-82-2) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 5-(trifluoromethyl)-pyridine-2-carboxylic acid methyl ester (124236-37-9)

Conditions	Yield
With triethylamine; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 at 80℃; under 3102.97 Torr; for 3h;	100%

tert-butyl (2-chloroethoxy)dimethyl silane (89031-81-2) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-(2-(tert-butyldimethylsilyloxy)ethylthio)-5-(trifluoromethyl)pyridine (1558056-06-6)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; Sodium thiosulfate pentahydrate; caesium carbonate In ethylene glycol; dimethyl sulfoxide at 120℃; Schlenk technique; Inert atmosphere; Green chemistry;	98%
With 1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; Sodium thiosulfate pentahydrate; caesium carbonate In ethylene glycol; dimethyl sulfoxide at 120℃; Inert atmosphere;	98%

(8R,9aS)-8-hydroxyoctahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride (1613630-17-3) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → (8R,9aS)-8-hydroxy-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one (1613630-18-4)

Conditions	Yield
With sodium carbonate In dimethyl sulfoxide at 100℃;	98%

potassium (2,4-difluorophenyl)trifluoroborate + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-(2',4'-difluorophenyl)-5-(trifluoromethyl)pyridine (387827-64-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 24h; Suzuki Coupling; Inert atmosphere; Sealed tube;	98%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 24h;	98%

S-Methylisothiourea sulfate (867-44-7) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-(methylthio)-5-(trifluoromethyl)pyridine (650592-47-5)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 1h;	98%

para-thiocresol (106-45-6) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-(p-tolylthio)-5-(trifluoromethyl)pyridine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 24h; Sealed tube; Inert atmosphere;	98%

5-(5-bromo-1-methyl-1H-pyrazol-4-yl)-7-methyl-4-(pyrrolidin-1-yl)imidazo[5,1-f][1,2,4]triazine + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 7-methyl-5-(1-methyl-5-(5-(trifluoromethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-4-(pyrrolidin-1-yl)imidazo[5,1-f][1,2,4]triazine

Conditions

Yield

Stage #1: 5-(5-bromo-1-methyl-1H-pyrazol-4-yl)-7-methyl-4-(pyrrolidin-1-yl)imidazo[5,1-f][1,2,4]triazine With TurboGrignard In tetrahydrofuran; 2-methyltetrahydrofuran at -10℃; for 1h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; 2-methyltetrahydrofuran at -10 - 20℃; for 1h; Inert atmosphere; Stage #3: 2-bromo-5-(trifluoromethyl)pyridine With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In tetrahydrofuran; 2-methyltetrahydrofuran at 80℃; for 22h; Inert atmosphere;

97%

4-(carbazol-9-yl)phenylboronic acid (419536-33-7) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 9-(4-(5-(trifluoromethyl)pyridin-2-yl)-phenyl)-9H-carbazole (1617519-03-5)

Conditions	Yield
With palladium diacetate; potassium carbonate In ethanol; water at 80℃;	96%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; N,N-dimethyl-formamide at 120℃; for 48h; Suzuki Coupling; Schlenk technique;	78%

3-chloro-5-(dihydroxyboryl)-1-(4-isopropoxyphenyl)-1H-indole-2-carboxylic acid ethyl ester (871829-81-1) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 3-chloro-1-(4-isopropoxyphenyl)-5-(5-trifluoromethylpyrid-2-yl)-1H-indole-2-carboxylic acid ethyl ester (871829-82-2)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; water; toluene at 85℃; for 3h;	95%
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; toluene at 85℃; for 3h; Product distribution / selectivity;	95%

2,4-difluorophenylboronic acid (144025-03-6) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-(2',4'-difluorophenyl)-5-(trifluoromethyl)pyridine (387827-64-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water for 36h; Reflux; Inert atmosphere;	95%
With potassium phosphate; methanesulfonic acid(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) In tetrahydrofuran; water at 40℃; for 4h; Inert atmosphere;	95%
With palladium diacetate; potassium carbonate; triphenylphosphine In ethanol; water; toluene Inert atmosphere; Reflux;	86%

2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) + 4-(diphenylamino)phenyl boronic acid (201802-67-7) → N-[4-(5-trifluoromethylpyridin-2-yl)phenyl]-N,N-diphenylamine

Conditions	Yield
With palladium diacetate; potassium carbonate In ethanol; water at 80℃; for 0.166667h; Suzuki Coupling;	95%
With palladium diacetate; potassium carbonate In ethanol; water at 80℃; Suzuki Coupling;
With palladium diacetate; potassium carbonate In ethanol; water at 80℃; Suzuki Coupling;

2,4-difluorophenylboronic acid (144025-03-6) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-(2,4-difluorophenyl)-4-(trifluoromethyl)pyridine

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran at 70℃; for 17h; Inert atmosphere; Schlenk technique;	95%

5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole-2-carboxylic acid ethyl ester (736990-02-6) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 5-(5-trifluoromethylpyrid-2-yl)-1H-indole-2-carboxylic acid ethyl ester (871829-38-8)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; water; toluene at 80℃; for 24h;	94%
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; toluene at 80℃; for 24h;	94%
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; toluene at 80℃; for 18h;	77%

methyl 2-[(tert-butoxycarbonyl)amino]acrylate (55477-80-0) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → C15H19F3N2O4

Conditions	Yield
With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate In water; dimethyl sulfoxide at 23℃; for 16h; Irradiation;	94%

5-bromo-2-methoxypyridine-3-carbonitrile (941294-54-8) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-methoxy-5-[5-(trifluoromethyl)-2-pyridyl]pyridine-3-carbonitrile

Conditions	Yield
Stage #1: 5-bromo-2-methoxypyridine-3-carbonitrile With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; bis(pinacol)diborane In 1,4-dioxane at 120℃; for 30h; Microwave irradiation; Stage #2: 2-bromo-5-(trifluoromethyl)pyridine With sodium carbonate In 1,4-dioxane; water at 100℃; for 0.5h; Microwave irradiation;	94%

4-azetidin-1-yl-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f ][1,2,4]triazine (1394034-58-2) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 4-(azetidin-1-yl)-7-methyl-5-(1-methyl-5-(5-(trifluoromethyl)pyridin-2-yl)-1H-pyrazol-4-yl)imidazo[5,1-f ][1,2,4]triazine (1394033-54-5)

Conditions	Yield
With potassium carbonate; bis(η3-allyl-μ-chloropalladium(II)) In 1,4-dioxane; dichloromethane at 102℃; for 36h; Inert atmosphere;	93%
With bis(η3-allyl-μ-chloropalladium(II)); potassium carbonate In 1,4-dioxane at 102℃; for 36h; Inert atmosphere; Reflux;	93%

thiophene boronic acid (6165-68-0) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-(thiophen-2-yl)-5-(trifluoromethyl)pyridine

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,2-dimethoxyethane; water at 80℃; for 14h;	93%

3-bromo-1H-pyrazole (14521-80-3) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-(3-bromo-1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 18h;	92.6%

1-(4-cyclopentyloxyphenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indole-2-carbonitrile (902772-15-0) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 1-(4-cyclopentyloxyphenyl)-5-(5-trifluoromethylpyridin-2-yl)-indole-2-carbonitrile (902772-16-1)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; water; toluene at 80℃; for 23h;	92%

isopropylamine (75-31-0) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → N-isopropyl-5-(trifluoromethyl)pyridin-2-amine (847240-94-2)

Conditions	Yield
at 100℃; for 8h; Sealed tube;	92%

2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) + (5-cyano-2-methoxyphenyl)boronic acid (612833-37-1) → 4-methoxy-3-[5-(trifluoromethyl)-2-pyridyl]benzonitrile

Conditions	Yield
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); sodium carbonate In water; N,N-dimethyl-formamide at 100℃; for 2h;	92%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In water; N,N-dimethyl-formamide at 100℃; for 2h;	92%

tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (375853-82-0, 286961-14-6) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → tert-butyl 5-(trifluoromethyl)-1,2,3,6-tetrahydro-[2,4-bipyridine]-1-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In water; toluene at 85℃; for 3h; Temperature; Solvent; Sealed tube; Inert atmosphere;	91.2%

4,4,5,5-tetramethyl-2-(2,2'',5,5''-tetramethyl-[3,2':3’,3''-terthiophen]-5'-yl)-1,3,2-dioxaborolane (1320351-63-0) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-(2,2'',5,5''-tetramethyl-[3,2':3',3''-terthiophen]-5'-yl)-5-(trifluoromethyl)-pyridine (1320351-72-1)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In tetrahydrofuran; water Suzuki coupling; Reflux;	91%
With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In tetrahydrofuran; water Inert atmosphere;

p-hydroxymethylphenylboronic acid (59016-93-2) + 1,2-diamino-benzene (95-54-5) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → C19H12F3N3

Conditions	Yield
With 5%-palladium/activated carbon; ammonium bicarbonate In water at 100℃; for 24h; Schlenk technique; Inert atmosphere; Green chemistry;	91%

1-dimesitylboryl-2-ethynylbenzene (1058722-73-8) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → C32H29BF3N

Conditions	Yield
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In tetrahydrofuran at 90℃; Schlenk technique; Inert atmosphere;	91%

2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 5-trifluoromethyl-pyridin-2-ylhydrazine (89570-85-4)

Conditions	Yield
With hydrazine hydrate In ethanol at 20 - 90℃;	90%
Stage #1: 2-bromo-5-(trifluoromethyl)pyridine With t-butoxycarbonylhydrazine; t-BuBrettPhos; [tBuBrettPhosPd(allyl)]OTf; sodium t-butanolate In water at 45℃; for 16h; Inert atmosphere; Stage #2: With sulfuric acid In ethanol; water at 90 - 95℃; Inert atmosphere; Sealed tube;

S-tert-butylsulfinimide (146374-27-8) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 2-methyl-N-(5-(trifluoromethyl)pyridin-2-yl)propane-2-sulfinamide (1338209-78-1)

Conditions	Yield
With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; for 15h; Inert atmosphere;	89%

(7R,8aS)-tert-butyl 7-hydroxyhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate (1204603-42-8) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → tert-butyl (7R,8aS)-7-{[5-(trifluoromethyl)pyridin-2-yl]oxy}hexahydro-pyrrolo[1,2-a]pyrazine-2(1H)-carboxylate (1429200-40-7)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 20℃; for 3h;	88%

1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine (5807-14-7) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → 1-(5-(trifluoromethyl)pyridin-2-yl)-2,3,4,6,7,8-hexahydro-pyrimido-[1,2-a]pyrimidine

Conditions	Yield
Stage #1: 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine; 2-bromo-5-(trifluoromethyl)pyridine With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 20℃; for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: With potassium tert-butylate In toluene at 90℃; for 5h; Schlenk technique; Inert atmosphere;	88%

tert-butyl (3R)-3-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-oxa-8-azaspiro[4.5]decane-8-carboxylate (1227473-84-8) + 2-bromo-5-(trifluoromethyl)pyridine (50488-42-1) → tert-butyl (3R)-3-(3-[5-(trifluoromethyl)pyridin-2-yl]phenyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylate (1227473-85-9)

Conditions	Yield
With sodium carbonate; bis-triphenylphosphine-palladium(II) chloride In water; acetonitrile at 85℃; Suzuki Coupling;	87%

Upstream product

• 624-28-2 2,5-dibromopyridine 
• 52334-81-3 2-chloro-5-trifluoromethylpyridine 
• 73290-22-9 2-bromo-5-iodo-pyridine 
• 81290-20-2 (trifluoromethyl)trimethylsilane 

Downstream Products

• 124236-37-9 5-(trifluoromethyl)-pyridine-2-carboxylic acid methyl ester 
• 871829-82-2 3-chloro-1-(4-isopropoxyphenyl)-5-(5-trifluoromethylpyrid-2-yl)-1H-indole-2-carboxylic acid ethyl ester 
• 27012-22-2 5-methyl-2-phenylpyridine 
• 866154-36-1 Ethyl 4-(5-trifluoromethylpyridin-2-yloxy)benzenecarboxylate 
• 248274-16-0 1-(5-(trifluoromethyl)pyridin-2-yl)ethan-1-one 
• 80194-69-0 5-(trifluoromethyl)picolinic acid 
• 902772-16-1 1-(4-cyclopentyloxyphenyl)-5-(5-trifluoromethylpyridin-2-yl)-indole-2-carbonitrile 
• 902765-93-9 3-formyl-1-(4-isopropoxyphenyl)-5-(5-trifluoromethylpyridin-2-yl)indole-2-carboxylic acid ethyl ester 
• 1057075-60-1 Ethyl 2-methyl-2-(4-(5-(trifluoromethyl)pyridin-2-yl)phenyl)propanoate 
• 874646-12-5 (3R)-3-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]piperazine 
• 863679-62-3 2-[1-(phenylmethyl)-2,5-dihydro-1H-pyrrol-3-yl]-5-(trifluoromethyl)pyridine 
• 95727-86-9 2-cyano-5-trifluoro-methylpyridine 

Relevant articles and documents

Recommendable routes to trifluoromethyl-substituted pyridine- and quinolinecarboxylic acids

As part of a case study, rational strategies for the preparation of all ten 2-, 3-, or 4-pyridinecarboxylic acids and all nine 2-, 3-, 4-, or 8-quinolinecarboxylic acids bearing trifluoromethyl substituents at the 2-, 3-, or 4-position were elaborated. The trifluoromethyl group, if not already present in the precursor, was introduced either by the deoxygenative fluorination of suitable carboxylic acids with sulfur tetrafluoride or by the displacement of ring-bound bromine or iodine by trifluoromethylcopper generated in situ. The carboxy function was produced by treatment of organolithium or organomagnesium intermediates, products of halogen/metal or hydrogen/ metal permutation, with carbon dioxide. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).