4-Chlorobutyronitrile

Last updated
4-Chlorobutyronitrile
3-ClC3H6CN.svg
Names
Other names
4-chlorobutanenitrile
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.010.029 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 211-031-6
PubChem CID
UNII
  • InChI=1S/C4H6ClN/c5-3-1-2-4-6/h1-3H2
    Key: ZFCFBWSVQWGOJJ-UHFFFAOYSA-N
  • C(CC#N)CCl
Properties
C4H6ClN
Molar mass 103.55 g·mol−1
Appearancecolorless liquid
Density 1.0934 g/cm3 @15 °C
Boiling point 189–191 °C (372–376 °F; 462–464 K)
Hazards
GHS labelling:
GHS-pictogram-skull.svg GHS-pictogram-exclam.svg
Danger
H301, H315, H319, H335
P261, P264, P270, P271, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501
Related compounds
Related compounds
3-Chloropropionitrile
Butyronitrile
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

4-Chlorobutyronitrile is the organic compound with the formula ClCH2CH2CH2CN. With both chloro and cyano functional groups, it is a bifunctional molecule. It is a colorless liquid.

Contents

Synthesis

Synthesis: 4-Chlorobutyronitrile synthesis.svg
Synthesis:

It is prepared by the reaction of potassium cyanide with 1-bromo-3-chloropropane.

Cyclopropyl cyanide is prepared by reaction of 4-chlorobutyronitrile with sodium amide in liquid ammonia. [2] However an increased yield was reported when the base/solvent mixture was changed to NaOH/DMSO. [3]

Drug Use

4-Chlorobutyronitrile is a precursor to the drugs buflomedil and buspirone. [4] Other known uses includes in the synthesis of MJ-7378 [21103-03-7], Tioperidone [52618-67-4], BP-897, NGB 2904, NGB 2849, FAUC 365, GR 103,691, Gepirone, Tandospirone, Tiospirone, CID:14086451 & Almotriptan.

Precursor

Synthesis: Stereoselective: 2-Phenylpyrrolidine synthesis.svg
Synthesis: Stereoselective:

4-Chlorobutyronitrile has been used as a starting material to prepare 2-Phenylpyrrolidine [1006-64-0]. This in turn is a chief precursor to a family of compounds called pyrroloisoquinolines. These are valuable agents in medicinal chemistry that are endowed with BAT subtrate reuptake inhibitor properties, elevating the synaptic concentration of serotonin and/or catecholamines. They therefore have application in the treatment of CNS diseases and eating disorders. A list of all of the known codenamed examples includes the following: JNJ-7925476, McN5652, Mcn-5292, Mcn 5707, McN-5908, McN 4612-z, McN-5558 & McN-5847.

More recently, an alternative synthetic protocol was also reported by Maryanoff. [7]

Related Research Articles

<span class="mw-page-title-main">Ketone</span> Organic compounds of the form >C=O

In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)–. The simplest ketone is acetone, with the formula CH3C(O)CH3. Many ketones are of great importance in biology and in industry. Examples include many sugars (ketoses), many steroids, and the solvent acetone.

<span class="mw-page-title-main">Imine</span> Organic compound or functional group containing a C=N bond

In organic chemistry, an imine is a functional group or organic compound containing a carbon–nitrogen double bond. The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bonds. Imines are common in synthetic and naturally occurring compounds and they participate in many reactions.

In organic chemistry, a nitrile is any organic compound that has a −C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, including methyl cyanoacrylate, used in super glue, and nitrile rubber, a nitrile-containing polymer used in latex-free laboratory and medical gloves. Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Organic compounds containing multiple nitrile groups are known as cyanocarbons.

<span class="mw-page-title-main">Anisole</span> Organic compound (CH₃OC₆H₅) also named methoxybenzene

Anisole, or methoxybenzene, is an organic compound with the formula CH3OC6H5. It is a colorless liquid with a smell reminiscent of anise seed, and in fact many of its derivatives are found in natural and artificial fragrances. The compound is mainly made synthetically and is a precursor to other synthetic compounds. Structurally, it is an ether with a methyl and phenyl group attached. Anisole is a standard reagent of both practical and pedagogical value.

<span class="mw-page-title-main">Trimethylaluminium</span> Chemical compound

Trimethylaluminium is one of the simplest examples of an organoaluminium compound. Despite its name it has the formula Al2(CH3)6 (abbreviated as Al2Me6 or TMA), as it exists as a dimer. This colorless liquid is pyrophoric. It is an industrially important compound, closely related to triethylaluminium.

An isocyanide is an organic compound with the functional group –N+≡C. It is the isomer of the related nitrile (–C≡N), hence the prefix is isocyano. The organic fragment is connected to the isocyanide group through the nitrogen atom, not via the carbon. They are used as building blocks for the synthesis of other compounds.

<span class="mw-page-title-main">Methyl vinyl ketone</span> Chemical compound

Methyl vinyl ketone (MVK, IUPAC name: butenone) is the organic compound with the formula CH3C(O)CH=CH2. It is a reactive compound classified as an enone, in fact the simplest example thereof. It is a colorless, flammable, highly toxic liquid with a pungent odor. It is soluble in water and polar organic solvents. It is a useful intermediate in the synthesis of other compounds.

<span class="mw-page-title-main">Cyclopropanation</span> Chemical process which generates cyclopropane rings

In organic chemistry, cyclopropanation refers to any chemical process which generates cyclopropane rings. It is an important process in modern chemistry as many useful compounds bear this motif; for example pyrethroids and a number of quinolone antibiotics. However, the high ring strain present in cyclopropanes makes them challenging to produce and generally requires the use of highly reactive species, such as carbenes, ylids and carbanions. Many of the reactions proceed in a cheletropic manner.

Acetone cyanohydrin (ACH) is an organic compound used in the production of methyl methacrylate, the monomer of the transparent plastic polymethyl methacrylate (PMMA), also known as acrylic. It liberates hydrogen cyanide easily, so it is used as a source of such. For this reason, this cyanohydrin is also highly toxic.

<span class="mw-page-title-main">Benzyl cyanide</span> Chemical compound

Benzyl cyanide (abbreviated BnCN) is an organic compound with the chemical formula C6H5CH2CN. This colorless oily aromatic liquid is an important precursor to numerous compounds in organic chemistry.

Organoiodine compounds are organic compounds that contain one or more carbon–iodine bonds. They occur widely in organic chemistry, but are relatively rare in nature. The thyroxine hormones are organoiodine compounds that are required for health and the reason for government-mandated iodization of salt.

<span class="mw-page-title-main">Dichlorophenylphosphine</span> Chemical compound

Dichlorophenylphosphine is an organophosphorus compound with the formula C6H5PCl2. This colourless viscous liquid is commonly used in the synthesis of organophosphines.

<span class="mw-page-title-main">Propionaldehyde</span> Chemical compound

Propionaldehyde or propanal is the organic compound with the formula CH3CH2CHO. It is the 3-carbon aldehyde. It is a colourless, flammable liquid with a slightly fruity odour. It is produced on a large scale industrially.

<span class="mw-page-title-main">Sodium chloroacetate</span> Chemical compound

Sodium chloroacetate is the organic compound with the formula CH2ClCO2Na. A white, water-soluble solid, it is the sodium salt of chloroacetic acid. Many of its uses are similar to those of the parent acid. It is prepared by treating chloroacetic acid with sodium carbonate.

<span class="mw-page-title-main">3-Chloropropionitrile</span> Chemical compound

3-Chloropropionitrile is an organic compound with the formula ClCH2CH2CN. A colorless liquid, it is prepared by the reaction of hydrogen chloride with acrylonitrile. It is used commercially as a precursor to the drug famotidine.

<span class="mw-page-title-main">Cyclopropyl cyanide</span> Chemical compound

Cyclopropyl cyanide is an organic compound consisting of a nitrile group as a substituent on a cyclopropane ring. It is the smallest cyclic compound containing a nitrile.

<span class="mw-page-title-main">1-Bromonaphthalene</span> Chemical compound

1-Bromonaphthalene is an organic compound with the formula C10H7Br.

<span class="mw-page-title-main">Cyclopropylacetylene</span> Chemical compound

Cyclopropylacetylene is an hydrocarbon with the chemical formula C
5
H
6
. Under normal conditions, the substance is a colorless liquid. Cyclopropylacetylene is a precursor pharmaceuticals and other organic compounds.

<span class="mw-page-title-main">Cyanoethylation</span>

Cyanoethylation is a process for the attachment of CH2CH2CN group to another organic substrate. The method is used in the synthesis of organic compounds.

1-Bromo-3-chloropropane is an organohalogen compound with the formula Br(CH2)3Cl. It is a colorless liquid, produced by free-radical addition of hydrogen bromide to allyl chloride. It is used as an alkylating agent to install the –(CH2)3Cl and –(CH2)3– groups. For example, it is a precursor to 4-chlorobutyronitrile.

References

  1. Charles F. H. Allen (1928). "γ-Chlorobutyronitrile". Organic Syntheses. 8: 52. doi:10.15227/orgsyn.008.0052.
  2. Schlatter, M. J. (1943). "Cyclopropyl Cyanide". Organic Syntheses. 23: 20. doi:10.15227/orgsyn.023.0020.
  3. J Bacha & C Selwitz, U.S. Patent 3,843,709 (1974 to Chevron USA Inc).
  4. Pollak, Peter; Romeder, Gérard; Hagedorn, Ferdinand; Gelbke, Heinz-Peter (2000). "Nitriles". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a17_363.
  5. Craig, L. C., Bulbrook, Helen., Hixon, R. M. (May 1931). "A GENERAL METHOD OF SYNTHESIS FOR ALPHA-SUBSTITUTED PYRROLINES AND PYRROLIDINES". Journal of the American Chemical Society. 53 (5): 1831–1835. doi:10.1021/ja01356a028.
  6. Zhang, Y., Kong, D., Wang, R., Hou, G. (2017). "Synthesis of chiral cyclic amines via Ir-catalyzed enantioselective hydrogenation of cyclic imines". Organic & Biomolecular Chemistry. 15 (14): 3006–3012. doi:10.1039/C7OB00442G.
  7. "N-VINYLPYRROLIDIN-2-ONE AS A 3-AMINOPROPYL CARBANION EQUIVALENT IN THE SYNTHESIS OF SUBSTITUTED 1-PYRROLINES: 2-PHENYL-1-PYRROLINE". Organic Syntheses. 75: 215. 1998. doi:10.15227/orgsyn.075.0215.