4-Chlorophenylacetonitrile
 | |
| Names | |
|---|---|
| Other names
p-Chlorobenzyl cyanide
| |
| Identifiers | |
3D model (JSmol)
|
|
| ChEBI | |
| ChemSpider | |
| ECHA InfoCard | 100.004.927 |
| EC Number |
|
| 1125640 | |
| KEGG | |
PubChem CID
|
|
| UNII | |
CompTox Dashboard (EPA)
|
|
| |
| |
| Properties | |
| C8H6ClN | |
| Molar mass | 151.59 g/mol |
| Density | 1.19g/cm3 |
| Melting point | 25–28 °C (77–82 °F; 298–301 K) |
| Boiling point | 265–267 °C (509–513 °F; 538–540 K) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
| |
4-Chlorophenylacetonitrile (sometimes referred to as 4-chlorobenzyl cyanide) is an organic compound that serves as a useful synthetic intermediate in medicinal chemistry. It is a chlorinated derivative of benzyl cyanide. The compound has a wide range of applications in the pharmaceutical industry and is also used in the synthesis of pesticides. It is toxic if ingested or absorbed through the skin,[1] and it acts as a chemical pollutant in the environment.[2]
Applications
[edit]Pharmaceuticals
[edit]4-Chlorophenylacetonitrile has beed used in the synthesis of:
Pesticides
[edit]4-Chlorophenylacetonitrile is sometimes used in the synthesis of 2-(4-chlorophenyl)-3-methyl butyric acid (aka fenvaleric acid [2012-74-0]).[10] This has use in the synthesis of fenvalerate.
Synthesis
[edit]196 g (4 mol) of sodium cyanide, 12.5 g (40 mmol) of tributylbenzylammonium chloride and 660 mL of water are initially introduced into a 2 l multineck apparatus with reflux condenser, internal thermometer and dropping funnel, and the mixture is heated to 90 °C. At the same temperature, 644 g (4 mol) of molten 4-chlorobenzyl chloride are added dropwise in 1 hr, and the mixture is then stirred for 2 hr. After having been cooled to about 35 °C., the organic phase is separated off, washed with water and fractionated over a short column. 552 g of 4-chlorobenzyl cyanide (91% of theory) are obtained.[11][12]
For alternative synthesis see:[13][14]
Reactions
[edit]- Hydrolysis of 4-chlorophenylacetonitrile gives 4-chlorophenylacetic acid [1878-66-6]. This has application in the synthesis of arhalofenate, clorindione, and metaglidasen
- Reduction of 4-chlorophenylacetonitrile gives 4-chlorophenethylamine [156-41-2]. This has application in the synthesis of lorcaserin.
Toxicity
[edit]4-Chlorophenylacetonitrile exhibits significant acute toxicity across multiple exposure routes. Oral administration in rats shows an LD50 of 50 mg/kg,[15][1] while intraperitoneal exposure in mice yields a lower LD50 of 27 mg/kg.[15] Skin exposure in rabbits demonstrates toxicity at 200 mg/kg (lowest lethal dose).[15] The compound is classified as Acute Toxicity Category 2-3 under GHS hazard statements, indicating fatal or toxic effects if swallowed, inhaled, or absorbed through skin.[2][16][1] It causes severe eye irritation (H319) and skin irritation (H315),[16][2] with additional respiratory risks from inhalation exposure (H335).[16] Regulatory data emphasize its Toxic designation for all primary exposure pathways, requiring strict handling precautions.[16][2][1]
References
[edit]- ^ a b c d "4-Chlorobenzyl cyanide". Safey Data Sheet. Thermo Fisher Scientific.
- ^ a b c d "4-Chloro Benzyl Cyanide" (PDF). Material Safety Data Sheet. CDH Fine Chemicals.
- ^ Castañer J, Roberts PJ (1977). "Halofenate". Drugs of the Future. 2 (7): 452. doi:10.1358/dof.1977.002.07.1002549.
- ^ US 8481597, Luskey K, Luo J, "Use of (-) (3-trihalomethylphenoxy) (4-halophenyl) acetic acid derivatives for treatment of insulin resistance, type 2 diabetes, hyperlipidemia and hyperuricemia", issued 9 July 2013, assigned to CymaBay Therapeutics Inc.
- ^ US 2935514, Hoffmann K, Hunger A, Kebrle J, Rossi A, "Benzimidazoles", issued 3 May 1960, assigned to Ciba Pharmaceutical Products Inc., Summit, N.J.
- ^ Lednicer D, Mitscher LA (13 May 1980). The Organic Chemistry of Drug Synthesis. John Wiley & Sons. p. 257. ISBN 978-0-471-04392-8.
- ^ DE 1905353, Walter LA, "New cyclic amidines, their therapeutic use and process for their preparation", issued 1969, assigned to Scherico Ltd.
- ^ US 3517051, Bolhofer WA, "Phenoxy substituted phenylacetic acids", issued 23 June 1970, assigned to Merck and Co Inc.
- ^ Jeffery JE, Kerrigan F, Miller TK, Smith GJ, Tometzki GB (1996). "Synthesis of sibutramine, a novel cyclobutylalkylamine useful in the treatment of obesity, and its major human metabolites". Journal of the Chemical Society, Perkin Transactions 1 (21): 2583. doi:10.1039/p19960002583.
- ^ US 5072037, Weber J, Lappe P, Springer H, "Process for the preparation of 2-(4-chlorophenyl)-3-methylbutyric acid", issued 10 December 1991, assigned to Hoechst AG
- ^ "Synthesis of 4-chlorobenzyl cyanide". PrepChem.
Literature source: US04650910
- ^ US 4650910, Henneke KW, Wedemeyer K, "Process for the preparation of substituted styrenes", issued 1987, assigned to Bayer AG
- ^ US 4056509, Verbrugge PA, Uurbanus EW, "Preparation of benzyl cyanides", issued 1 November 1977, assigned to Shell USA Inc.
- ^ Sera A, Tani H, Nishiguchi I, Hirashima T (1987). "A Facile Synthesis of Nitriles from 1-Nitro-1-alkenes by Electroreduction". Synthesis. 1987 (7): 631–633. doi:10.1055/s-1987-28028.
- ^ a b c "4-Chlorophenylacetonitrile" (PDF). Safety Data Sheet. TCI Chemicals.
- ^ a b c d "4-Chlorophenylacetonitrile". PubChem. U.S. National Library of Medicine.