258506-66-0

Basic information

• Product Name: 2-Chloro-6-iodopyridine
• Synonyms: 2-CHLORO-IODOPYRIDINE;2-CHLORO-6-IODO-PYRIDINE;Chloroiodopyridine 26----;6-Iodo-2-chloro-pyridine
• CAS NO: 258506-66-0
• Molecular Formula: C₅H₃ClIN
• Molecular Weight: 239.44
• EINECS: 145-896-5
• Product Categories: compounds of pyridine;Halides;Pyridines
• Mol File: 258506-66-0.mol
• Article Data: 7

Chemical Properties

• Melting Point: 42-43 °C(lit.)
• Boiling Point: 255 ºC
• Flash Point: 108 ºC
• Appearance: /
• Density: 2.052
• Vapor Pressure: 0.026mmHg at 25°C
• Refractive Index: 1.642
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: -2.84±0.10(Predicted)
• CAS DataBase Reference: 2-Chloro-6-iodopyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-6-iodopyridine(258506-66-0)
• EPA Substance Registry System: 2-Chloro-6-iodopyridine(258506-66-0)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-41-43
• Safety Statements: 26-36/37/39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 258506-66-0(Hazardous Substances Data)

Usage

Description

2-Chloro-6-iodopyridine is an organic compound characterized by the presence of a pyridine ring with a chlorine atom at the 2nd position and an iodine atom at the 6th position. It is a versatile building block in the synthesis of various chemical compounds and has potential applications in the pharmaceutical and chemical industries due to its unique structural features.

Uses

Used in Pharmaceutical Industry:
2-Chloro-6-iodopyridine is used as a reagent for the synthesis of ruthenium half-sandwich complexes, which are known to serve as protein kinase inhibitors. These complexes play a crucial role in the development of targeted therapies for various diseases, including cancer, by modulating the activity of specific protein kinases involved in cellular signaling pathways.
In the synthesis of these ruthenium complexes, 2-chloro-6-iodopyridine acts as a key intermediate, providing the necessary structural framework and functional groups for the formation of the final product. The unique combination of chlorine and iodine atoms in the molecule allows for further functionalization and modification, enabling the development of a diverse range of ruthenium complexes with tailored properties and applications.
Furthermore, the use of 2-chloro-6-iodopyridine in the synthesis of these complexes highlights its importance as a building block in the design and development of novel therapeutic agents. Its versatility and reactivity make it a valuable component in the ongoing efforts to create more effective and targeted treatments for a wide range of diseases.

InChI:InChI=1/C5H3ClIN/c6-4-2-1-3-5(7)8-4/h1-3H

Synthetic route

2-chloropyridine (109-09-1) → 2-chloro-5-iodo-pyridine (258506-66-0)

Conditions	Yield
With n-butyllithium; 2-(N,N-dimethylamino)ethanol; iodine at -78℃;	91%
Stage #1: 2-chloropyridine With n-butyllithium; BuLi-LiDMAE In hexane at -78℃; for 1h; Metallation; Stage #2: With iodine In tetrahydrofuran at -78 - 0℃; for 1h; Condensation;	80%
With n-butyllithium; iodine; lithium 2-(dimethylamino)ethanolate	80%

2-bromo-6-chloro-pyridine (5140-72-7) → 2-chloro-5-iodo-pyridine (258506-66-0)

Conditions	Yield
Stage #1: 2-bromo-6-chloro-pyridine With n-butyllithium In diethyl ether; hexane at -75℃; for 0.75h; Stage #2: With iodine In tetrahydrofuran; diethyl ether; hexane at -75℃; for 0.75h;	84%
Stage #1: 2-bromo-6-chloro-pyridine With n-butyllithium In diethyl ether at -78℃; for 1h; Inert atmosphere; Schlenk technique; Stage #2: With iodine at 20℃; for 12h; Inert atmosphere; Schlenk technique;	80%

2-chloropyridine (109-09-1) → 2-chloro-4-iodopyridine (153034-86-7) + 2-chloro-3,6-diiodopyridine + 2-chloro-3-iodopyridine (78607-36-0) + 2-chloro-5-iodo-pyridine (258506-66-0)

Conditions	Yield
Stage #1: 2-chloropyridine With 2,2,6,6-tetramethyl-piperidine; n-butyllithium; ZnCl2-N,N,N’,N’-tetramethylethylenediamine In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran Inert atmosphere; regioselective reaction;	A 9 %Spectr. B 15% C 43 %Spectr. D 30%

2-chloropyridine (109-09-1) → 2-chloro-4-iodopyridine (153034-86-7) + 2,5-di-iodopyridine (116195-81-4) + 2-chloro-3,6-diiodopyridine + 2-chloro-3-iodopyridine (78607-36-0) + 2-chloro-5-iodo-pyridine (258506-66-0)

Conditions	Yield
Stage #1: 2-chloropyridine With 2,2,6,6-tetramethyl-piperidine; n-butyllithium; ZnCl2-N,N,N’,N’-tetramethylethylenediamine In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran Inert atmosphere; regioselective reaction;	A 6 %Spectr. B 4% C 3% D 41 %Spectr. E 10%

2,6-dichloropyridine (2402-78-0) → 2,6-diiodo-pyridine (53710-17-1) + 2-chloro-5-iodo-pyridine (258506-66-0)

Conditions	Yield
With hydrogen iodide; sodium iodide at 100℃; for 14h; Substitution; Title compound not separated from byproducts;

2,6-Dibromopyridine (626-05-1) → 2-chloro-5-iodo-pyridine (258506-66-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: iPrMgCl / tetrahydrofuran / 2 h / 0 - 25 °C 1.2: 73 percent / CF2ClCFCl2 / tetrahydrofuran / 1.75 h / 0 - 25 °C 2.1: nBuLi / diethyl ether; hexane / 0.75 h / -75 °C 2.2: 84 percent / I2 / hexane; diethyl ether; tetrahydrofuran / 0.75 h / -75 °C View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / diethyl ether / 1 h / -78 °C / Inert atmosphere; Schlenk technique 1.2: 12 h / 20 °C / Inert atmosphere; Schlenk technique 2.1: n-butyllithium / diethyl ether / 1 h / -78 °C / Inert atmosphere; Schlenk technique 2.2: 12 h / 20 °C / Inert atmosphere; Schlenk technique View Scheme

p-methylazidobenzene (2101-86-2) + 2-chloro-5-iodo-pyridine (258506-66-0) → 6-chloro-N-(p-tolyl)pyridin-2-amine

Conditions	Yield
With nickel(II) bromide dimethoxyethane; diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; tris(2,2′-bipyridyl)dichlororuthenium(II) hexahydrate; bathophenanthroline; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 27℃; for 20h; Irradiation;	98%

p-tolyltriethoxysilane (18412-57-2) + 2-chloro-5-iodo-pyridine (258506-66-0) → 2-chloro-6-(4-methylphenyl)pyridine (864913-65-5) + 6,6'-dichloro-2,2'-bipyridine (53344-72-2)

Conditions	Yield
With copper(l) iodide; cesium fluoride In N,N-dimethyl-formamide at 120℃; for 12h; Hiyama Coupling; Inert atmosphere;	A 70% B n/a

1,2-propanediene (463-49-0) + benzoyl chloride (98-88-4) + 2-chloro-5-iodo-pyridine (258506-66-0) → N-[2-(6-chloro-pyridin-2-yl)-allyl]-benzamide

Conditions	Yield
Stage #1: 1,2-propanediene; 2-chloro-5-iodo-pyridine With trifuran-2-yl-phosphane; Fmoc-deprotected Rink Amide MBHA resin; potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0) In N,N-dimethyl-formamide at 80℃; for 24h; Stage #2: benzoyl chloride With triethylamine In dichloromethane at 0 - 20℃; for 24h; Stage #3: With trifluoroacetic acid In dichloromethane at 20℃; for 0.333333h;	68%

N-Boc-indole-2-boronic acid (213318-44-6) + 2-chloro-5-iodo-pyridine (258506-66-0) → C13H9ClN2 (937810-25-8)

Conditions	Yield
Stage #1: N-Boc-indole-2-boronic acid; 2-chloro-5-iodo-pyridine With sodium carbonate; bis(triphenylphosphine)palladium(II)-chloride In 1,2-dimethoxyethane; water Suzuki cross-coupling reaction; Heating; Stage #2: With silica gel In dichloromethane at 80℃; Further stages.;	66%

triethylamine (121-44-8) + 2-chloro-5-iodo-pyridine (258506-66-0) → 2-chloro-6-acetylpyridine

Conditions	Yield
With water; oxygen; zinc(II) oxide In acetonitrile at 20℃; Irradiation;	62%

(trifluoromethyl)trimethylsilane (81290-20-2) + 2-chloro-5-iodo-pyridine (258506-66-0) → 2-chloro-6-trifluoromethylpyridine

Conditions	Yield
With potassium fluoride; copper(l) iodide In 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide at 25℃; for 6h;	59%

Conditions	Yield
Stage #1: 2-chloro-5-iodo-pyridine With 3-chloro-benzenecarboperoxoic acid In chloroform at 20℃; Stage #2: toluene-4-sulfonic acid; methoxybenzene at 40℃; for 2h;	59%

Conditions	Yield
In toluene at 80℃; for 24h;	56%

+ 1,2-propanediene (463-49-0) + 2-chloro-5-iodo-pyridine (258506-66-0) → ethyl (2S)-4-(6-chloro-pyridin-2-yl)-2-(2-methyl-prop-2-yl-(S)-sulfinylamino)-pent-4-enoate (879571-96-7)

Conditions	Yield
With piperidine; copper(l) iodide; trifuran-2-yl-phosphane; palladium diacetate; indium In N,N-dimethyl-formamide at 40℃; under 375.03 Torr; for 24h;	52%

1,2-propanediene (463-49-0) + 2-chloro-5-iodo-pyridine (258506-66-0) + ethyl ((RS)-N-tert-butylsulfinyl)iminoacetate (960133-71-5) → ethyl (2R)-4-(6-chloro-pyridin-2-yl)-2-(2-methyl-prop-2-yl-(R)-sulfinylamino)-pent-4-enoate (879571-97-8)

Conditions	Yield
With piperidine; copper(l) iodide; trifuran-2-yl-phosphane; palladium diacetate; indium In N,N-dimethyl-formamide at 40℃; under 375.03 Torr; for 24h;	49%

2-methyl-but-3-yn-2-ol (115-19-5) + 2-chloro-5-iodo-pyridine (258506-66-0) → 2-chloro-6-(3-methyl-3-hydroxybutynyl)pyridine

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine In triethylamine at 20℃; for 24h; Substitution;	47%

phenylacetylene (536-74-3) + 2-chloro-5-iodo-pyridine (258506-66-0) → 2-chloro-6-(2-phenylethynyl)pyridine

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine In triethylamine at 20℃; for 24h; Substitution;	46%

tert-butyl-3-iodoazetidine-1-carboxylate (254454-54-1) + 2-chloro-5-iodo-pyridine (258506-66-0) → tert-butyl 3-(6-chloropyridin-2-yl)azetidine-1-carboxylate

Conditions	Yield
Stage #1: tert-butyl-3-iodoazetidine-1-carboxylate With chloro-trimethyl-silane; zinc In tetrahydrofuran; ethylene dibromide at 20℃; for 2h; Inert atmosphere; Stage #2: 2-chloro-5-iodo-pyridine With tris-(dibenzylideneacetone)dipalladium(0); trifuran-2-yl-phosphane In tetrahydrofuran; ethylene dibromide at 60℃; for 16h; Inert atmosphere;	42.14%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 2-chloro-5-iodo-pyridine (258506-66-0) → 6-chloropyridine-2-carboxaldehyde (54087-03-5)

Conditions	Yield
With n-butyllithium	42%

Diphenylphosphine oxide (4559-70-0) + 2-chloro-5-iodo-pyridine (258506-66-0) → pyridine-2,6-diylbis(diphenylphosphine oxide) (64741-31-7)

Conditions	Yield
With potassium tert-butylate In acetonitrile at 20℃; for 6h; Inert atmosphere; Irradiation;	38%

4-ethynyl-5-methyl-1-(6-methylpyridin-3-yl)-1H-imidazole-2-carboxamide + 2-chloro-5-iodo-pyridine (258506-66-0) → 4-((6-chloropyridin-2-yl)ethynyl)-5-methyl-1-(6-methylpyridin-3-yl)-1H-imidazole-2-carboxamide

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 0 - 23℃; for 4h; Sonogashira Cross-Coupling; Inert atmosphere;	33%

C10H15BrOSn + 2-chloro-5-iodo-pyridine (258506-66-0) → C12H9BrClNO

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0) In toluene for 48h; Inert atmosphere; Schlenk technique; Reflux;	19%

2-chloro-5-iodo-pyridine (258506-66-0) + tert-butyl (1S,4R)-2-azabicyclo[2.2.1]heptan-5-en-2-carboxylate (702666-72-6) → (1R,4R,5R)-5-(6-Chloro-pyridin-3-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester + (1S,4S,6R)-6-(6-Chloro-pyridin-3-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) reductive Heck conditions; Yield given;

2-chloro-5-iodo-pyridine (258506-66-0) + benzyl (1S,4R)-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate → (1S,4S,6R)-6-(6-Chloro-pyridin-3-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid benzyl ester + (1R,4R,5R)-5-(6-Chloro-pyridin-3-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid benzyl ester

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) reductive Heck conditions; Yield given;

2-methyl-but-3-yn-2-ol (115-19-5) + 2-chloro-5-iodo-pyridine (258506-66-0) → 2-chloro-6-(2'-thienylpyridine) (35299-70-8)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane at 100℃; for 6h; Substitution;

2-chloro-5-iodo-pyridine (258506-66-0) → (2R,5R)-(-)-1-(6-tert-butoxypyrid-2-yl)-1-oxo-2,5-diphenylphospholane (949160-19-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 56 percent / toluene / 24 h / 80 °C 2: iPr2NEt; 1,3-bis(diphenylphosphanyl)propane / Pd(trans,trans-dibenzylideneacetone)2 / dimethylformamide / 18 h / 105 °C View Scheme

2-chloro-5-iodo-pyridine (258506-66-0) → (2S,5S)-(-)-1-(6-tert-butoxypyrid-2-yl)-1-oxo-2,5-diphenylphospholane (949575-86-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 56 percent / toluene / 24 h / 80 °C 2: 64 percent / iPr2NEt; 1,3-bis(diphenylphosphanyl)propane / Pd(trans,trans-dibenzylideneacetone)2 / dimethylformamide / 18 h / 105 °C View Scheme

2-chloro-5-iodo-pyridine (258506-66-0) → C25H29BNOP

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 56 percent / toluene / 24 h / 80 °C 2.1: iPr2NEt; 1,3-bis(diphenylphosphanyl)propane / Pd(trans,trans-dibenzylideneacetone)2 / dimethylformamide / 18 h / 105 °C 3.1: methyl triflate / 1,2-dimethoxy-ethane / 2 h 3.2: LiAlH4 / 1,2-dimethoxy-ethane / 1.5 h / 20 °C 3.3: 60 percent / BH3*SMe2 / toluene / 15 h View Scheme

2-chloro-5-iodo-pyridine (258506-66-0) → C25H29BNOP

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 56 percent / toluene / 24 h / 80 °C 2.1: 64 percent / iPr2NEt; 1,3-bis(diphenylphosphanyl)propane / Pd(trans,trans-dibenzylideneacetone)2 / dimethylformamide / 18 h / 105 °C 3.1: methyl triflate / 1,2-dimethoxy-ethane / 2 h 3.2: LiAlH4 / 1,2-dimethoxy-ethane / 1.5 h / 20 °C 3.3: 60 percent / BH3*SMe2 / toluene / 15 h View Scheme

2-chloro-5-iodo-pyridine (258506-66-0) → (2R,5R)-(-)-6-(tert-butoxypyrid-2-yl)-2,5-diphenylphospholane (949160-25-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 56 percent / toluene / 24 h / 80 °C 2.1: iPr2NEt; 1,3-bis(diphenylphosphanyl)propane / Pd(trans,trans-dibenzylideneacetone)2 / dimethylformamide / 18 h / 105 °C 3.1: methyl triflate / 1,2-dimethoxy-ethane / 2 h 3.2: LiAlH4 / 1,2-dimethoxy-ethane / 1.5 h / 20 °C 3.3: 60 percent / BH3*SMe2 / toluene / 15 h 4.1: 74 percent / DABCO / tetrahydrofuran / 2 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 56 percent / toluene / 24 h / 80 °C 2: iPr2NEt; 1,3-bis(diphenylphosphanyl)propane / Pd(trans,trans-dibenzylideneacetone)2 / dimethylformamide / 18 h / 105 °C 3: HSiCl3; NEt3 / acetonitrile / 24 h / Heating View Scheme

Upstream product

• 2402-78-0 2,6-dichloropyridine 
• 109-09-1 2-chloropyridine 
• 626-05-1 2,6-Dibromopyridine 
• 5140-72-7 2-bromo-6-chloro-pyridine 

Downstream Products

• 152356-57-5 1-(6-chloropyridin-2-yl)ethan-1-one 
• 64741-31-7 pyridine-2,6-diylbis(diphenylphosphine oxide) 
• 1220017-99-1 6-chloro-N-(p-tolyl)pyridin-2-amine 
• 54087-03-5 6-chloropyridine-2-carboxaldehyde 
• 864913-65-5 2-chloro-6-(4-methylphenyl)pyridine 
• 53344-72-2 6,6'-dichloro-2,2'-bipyridine 
• 1401527-40-9 (6-chloropyridin-2-yl)(4’-methoxyphenyl)iodonium tosylate 
• 949575-78-4 (2S,5S)-(+)-6-(tert-butoxypyrid-2-yl)-2,5-diphenylphospholane 
• 949160-25-2 (2R,5R)-(-)-6-(tert-butoxypyrid-2-yl)-2,5-diphenylphospholane 
• 949575-86-4 (2S,5S)-(-)-1-(6-tert-butoxypyrid-2-yl)-1-oxo-2,5-diphenylphospholane 
• 949160-19-4 (2R,5R)-(-)-1-(6-tert-butoxypyrid-2-yl)-1-oxo-2,5-diphenylphospholane 
• 39890-95-4 2-chloro-6-trifluoromethylpyridine 

Relevant articles and documents

Synthesis and spectroscopic characterization of group 4 post-metallocenes bearing (σ-aryl)-2-phenolate-6-pyridyl and -isoquinolinyl auxiliaries

A new series of group 4 bis(benzyl) complexes supported by (σ-aryl)-2-phenolate-6-pyridyl [O,C,N] ligands have been prepared, and all derivatives have been characterized by multinuclear NMR spectroscopy. In the 1H NMR spectrum of the Ti derivative where [N] = (ortho-F)-substituted isoquinolinyl, one of the two CH2 resonances is observed as a doublet of doublets (collapsing to a normal d upon 19F-decoupling), whereas the [1H,19F]-HMQC correlation spectrum reveals a strong crosspeak for this dd resonance only, thus indicating the presence of intramolecular C-H·F-C interactions. [1H,19F]-HMBC experiments have been performed which reveal a significant scalar component for this coupling and confirm that the interactions are genuine. The contrasting NMR spectral patterns for the (ortho-F)-pyridyl Hf analogue, which exhibits two sets of non-identical doublet of doublets for the methylene resonances, have been rationalized. The activities of the isoquinolinyl-based Ti-[O,C,N] catalysts for ethylene polymerization are superior to those of pyridyl-based congeners.

Deprotonative metalation of chloro- and bromopyridines using amido-based bimetallic species and regioselectivity-computed CH acidity relationships

A series of chloro- and bromopyridines have been deprotometalated by using a range of 2,2,6,6-tetramethylpiperidino-based mixed lithium-metal combinations. Whereas lithium-zinc and lithium-cadmium bases afforded different mono- and diiodides after subsequent interception with iodine, complete regioselectivities were observed with the corresponding lithium-copper combination, as demonstrated by subsequent trapping with benzoyl chlorides. The obtained selectivities have been discussed in light of the CH acidities of the substrates, determined both in the gas phase and as a solution in THF by using the DFT B3LYP method.

Trifluoromethyl-substituted pyridines through displacement of iodine by in situ generated (trifluoromethyl)copper

A literature method reported for iodobenzene and congeners was successfully extended to the pyridine series. 2-Iodopyridines can be converted into 2-(trifluoromethyl)pyridines almost quantitatively. In contrast, yields are moderate at best if 3- and 4-iodopyridines or 2-bromopyridines are used as the starting materials. WILEY-VCH Verlag GmbH 2002.