2-Chloropyridine

2-Chloropyridine
Identifiers
CAS number	109-09-1 Y
ChemSpider	7689 Y
ChEBI	CHEBI:39174 Y
ChEMBL	CHEMBL509579 Y
Jmol-3D images	Image 1
SMILES Clc1ncccc1
InChI InChI=1S/C5H4ClN/c6-5-3-1-2-4-7-5/h1-4H Y Key: OKDGRDCXVWSXDC-UHFFFAOYSA-N Y InChI=1/C5H4ClN/c6-5-3-1-2-4-7-5/h1-4H Key: OKDGRDCXVWSXDC-UHFFFAOYAI
Properties
Molecular formula	C5H4ClN
Molar mass	113.54 g/mol
Appearance	colorless, clear liquid
Melting point	-46 °C, 227 K, -51 °F
Boiling point	166 °C, 439 K, 331 °F
Solubility in water	27 g/L
Acidity (pKa)	0.49 [1]
Hazards
MSDS	MSDS
R-phrases	R23 R38
S-phrases	S26 S37 S39 S45
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

2-Chloropyridine is an organohalide with the formula C₅H₄ClN. It is primarily used to generate fungicides and insecticides in industry. It also serves to generate antihistamines and antiarrythymics for pharmaceutical purposes.^[2]

Preparation

2-Choropyridine was originally synthesized in 1898 by the chlorination of 2-hydroxypyridine.^[3]

2-Chloropyridine can also be generated by halogenating pyridine. This reaction proceeds under heating by the direct chlorination of pyridine by molecular chlorine to afford a mixture of 2-chloropyridine and 2,6-dichloropyridine.^[2]

Another synthesis is to chlorinate pyridinol with phosporyl chloride.^[2]

Alternatively, 2-chloropyridines can be conveniently synthesized in high yields from pyridine-N-oxides.^[4]

Structure and properties

2-Chloropyridine reacts with nucleophiles to generate pyridine derivatives substituted at the second and fourth carbons on the heterocycle. Therefore, many reactions using 2-chloropyridine generate mixtures of products which require further workup to isolate the desired isomer.^[2]

Main reactions and applications

2-chloropyridine is primarily used to generate other pyridine derivatives. Some commercial products include pyrithione, pyripropoxyfen, chlorphenamine, and disopyramide. These reactions rely on chloride’s nature as a good leaving group to facilitate the transfer of a substrate onto the pyridine ring.^[2] Pyrithione, the conjugate base of 2-mercaptopyridine-N-oxide, is a fungicide found in some shampoos. It is generated from 2-chloropyridine by reacting the N-oxide of 2-chloropyridine with Na₂S in a basic solution, before adding aqueous HCl.^[5] Used as an antihistamine, pheniramine may be generated via several different pathways. One synthesis is to hydroformylate functionalized olefins. This reaction proceeds by reacting phenylacetonitrile with 2-chloropyridine in the presence of a base. The resulting intermediate is then alkylated by 2-(dimethylamino)ethyl chloride and the cyano group removed.^[6]

Environmental Properties

Though pyridine is an excellent source of carbon, nitrogen, and energy for certain microorganisms, introduction of a halogen moiety significantly retards degradation of the pyridine ring. With the exception of 4-chloropyridine, each of the mono- and di-substituted chloropyridines were found to be relatively resistant to microbiological degradation in soil or liquid media.^[7] Estimated time for complete degradation was > 30 days. 2-Chloropyridine exhibits extensive volatilization losses from water, less so when present in soil.^[8]

References

1. ^ Linnell, R. H., J. Org. Chem., 1960, 25, 290.
2. ^ ^{a b c d e} Shimizu, Shinkichi et al. Pyridine and Pyridine Derivatives. Ullmann’s Encyclopedia of Industrial Chemistry. 2000. DOI: 10.1002/14356007.a22_399
3. ^ Sell, William J.; Dootson, Frederick W. The chlorine derivatives of pyridine. Part I. Journal of the Chemical Society, Transactions. 1898, 73, pp. 432-441. http://www.rsc.org/ejarchive/CT/1898/CT8987300432.pdf
4. ^ P. Naender, B. Gangadasu, Chilukuri Ramesh, B.C. Raju and V.J. Rao. Facile and Selective Synthesis of Chloromethypyridines and Chloropyridines using Diphosgene/Triphosgene. Synthetic Communications. 34, 6, 1097, 2004
5. ^ Cheng, Hefeng; She, Ji. 14. Improved preparation of 2-mercaptopyridine-N-oxide. Zhongguo Yiyao Gongye Zazhi. 1990, 21, (2), pp. 55-56. ISSN: 1001-8255
6. ^ Botteghi, Carlo et al. New Synthetic Route to Pheniramines via Hydroformylation of Functionalyzed Olefins. 1994, 59, pp. 7125-7127. DOI: 10.1021/jo00102a044
7. ^ Sims, G. K. and L.E. Sommers. 1986. Biodegradation of pyridine derivatives in soil suspensions. Environmental Toxicology and Chemistry. 5:503-509.
8. ^ Sims, G. K. and L.E. Sommers. 1985. Degradation of pyridine derivatives in soil. Journal of Environmental Quality. 14:580-584.