 | |
 | |
| Names | |
|---|---|
| Preferred IUPAC name Phenylmethanamine | |
| Other names α-Aminotoluene Benzyl amine Phenylmethylamine | |
| Identifiers | |
| |
3D model (JSmol) | |
| 741984 | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
|
| DrugBank |
|
| ECHA InfoCard | 100.002.595 |
| EC Number |
|
| 49783 | |
| KEGG |
|
| RTECS number |
|
| UNII | |
| UN number | 2735 |
| |
| |
| Properties | |
| C7H9N | |
| Molar mass | 107.156 g·mol−1 |
| Appearance | Colorless liquid |
| Odor | weak,ammonia-like |
| Density | 0.981 g/mL[1] |
| Melting point | 10 °C (50 °F; 283 K)[2] |
| Boiling point | 185 °C (365 °F; 458 K)[2] |
| Miscible[2] | |
| Solubility | miscible inethanol,diethyl ether very soluble inacetone soluble inbenzene,chloroform |
| Acidity (pKa) | 9.34[3] |
| Basicity (pKb) | 4.66 |
| −75.26·10−6 cm3/mol | |
Refractive index (nD) | 1.543 |
| Structure | |
| 1.38D | |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards | Flammable and corrosive |
| GHS labelling: | |
  | |
| Danger | |
| H302,H312,H314 | |
| P260,P264,P270,P280,P301+P312,P301+P330+P331,P302+P352,P303+P361+P353,P304+P340,P305+P351+P338,P310,P312,P321,P322,P330,P363,P405,P501 | |
| NFPA 704 (fire diamond) | |
| Flash point | 65 °C (149 °F; 338 K)[2][1] |
| Safety data sheet (SDS) | Fischer Scientific |
| Related compounds | |
Relatedamines | aniline |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Benzylamine, also known asphenylmethylamine, is anorganicchemical compound with thecondensed structural formula C6H5CH2NH2 (sometimes abbreviated asPhCH2NH2 orBnNH2). It consists of abenzyl group, C6H5CH2, attached to an aminefunctional group, NH2. This colorless water-soluble liquid is a common precursor inorganic chemistry and used in the industrial production of manypharmaceuticals. Thehydrochloride salt was used to treatmotion sickness on theMercury-Atlas 6 mission in whichNASA astronautJohn Glenn became the first American to orbit the Earth.
Benzylamine can be produced by several methods, the main industrial route being the reaction ofbenzyl chloride andammonia. It is also produced by the reduction ofbenzonitrile andreductive amination ofbenzaldehyde, both done overRaney nickel.[4]
It was first produced accidentally byRudolf Leuckart in the reaction of benzaldehyde withformamide in a process now known as theLeuckart reaction.[5]
Benzylamine occurs biologically from the action of theN-substituted formamide deformylase enzyme, which is produced byArthrobacter pascens bacteria.[6] Thishydrolase catalyses the conversion ofN-benzylformamide into benzylamine withformate as a by-product.[7] Benzylamine is degraded biologically by the action of themonoamine oxidase Benzyme,[8] resulting in benzaldehyde.[9]
Benzylamine is used as a masked source ofammonia, since afterN-alkylation, the benzyl group can be removed byhydrogenolysis:[10]
Typically a base is employed in the first step to absorb the HBr (or related acid for other kinds of alkylating agents).
Benzylamine reacts withacetyl chloride to formN-benzylacetamide.
Isoquinolines can be prepared from benzylamine andglyoxalacetal by an analogous approach known as the Schlittler-Müller modification to the Pomeranz–Fritsch reaction. This modification can also be used for preparing substituted isoquinolines.[11]
Benzylamine is used in the manufacture of other pharmaceuticals, includingalniditan,[12]lacosamide,[13][14]moxifloxacin,[15] andnebivolol.[16]
Benzylamine is also used to manufacture the military explosivehexanitrohexaazaisowurtzitane (HNIW), which is superior to oldernitroaminehigh explosives likeHMX andRDX. Illustrating the debenzylation tendency of benzylamines, four of the benzyl groups are removed from hexabenzylhexaazaisowurtzitane by hydrogenolysis catalysed bypalladium on carbon.[17]
Benzylamine has been found to act as amonoamine oxidase inhibitor (MAOI), including of bothmonoamine oxidase A (MAO-A) andmonoamine oxidase B (MAO-B).[18]
Aderivative,pargyline (N-methyl-N-propargylbenzylamine), is an MAOI that has been usedpharmaceutically as anantihypertensive agent andantidepressant.[19]α-Methylbenzylamine (1-phenylethylamine) is an MAOI, inhibiting both MAO-A and MAO-B, as well.[18]
Another derivative,α,N-DMMDBA (MDM1EA; α,N-dimethyl-3,4-methylenedioxybenzylamine), partially substitutes forMDMA at high doses indrug discrimination tests in rats.[20][21] Benzylamine is also similar instructure tobenzylpiperazine (BZP), which is amonoamine releasing agent andpsychostimulant.[22] However, both benzylamine and α-methylbenzylamine have been found to be inactive asnorepinephrine releasing agents.[23]
Thehydrochloridesalt of benzylamine, C6H5CH2NH3Cl or C6H5CH2NH2·HCl,[24] is prepared by reacting benzylamine withhydrochloric acid, and can be used in treatingmotion sickness.NASA astronautJohn Glenn was issued with benzylamine hydrochloride for this purpose for theMercury-Atlas 6 mission.[25] The cation in this salt is called benzylammonium and is a moiety found in pharmaceuticals such as theanthelmintic agentbephenium hydroxynaphthoate, used in treatingascariasis.[26]
Other derivatives of benzylamine and its salts have been shown to haveanti-emetic properties, including those with theN-(3,4,5-trimethoxybenzoyl)benzylamine moiety.[27] Commercially available motion-sickness agents includingcinnarizine andmeclizine are derivatives of benzylamine.
1-Phenylethylamine is amethylated benzylamine derivative that ischiral;enantiopure forms are obtained byresolvingracemates. Its racemic form is sometimes known as (±)-α-methylbenzylamine.[28] Both benzylamine and 1-phenylethylamine form stable ammonium salts and imines due to their relatively highbasicity.
Benzylamine exhibits modest oral toxicity in rats withLD50 of 1130 mg/kg. It is readily biodegraded.[4]
The β-phenethylamine skeleton is a critical feature of the molecule since either increasing or decreasing the number of carbons between the phenyl ring and the nitrogen reduced or abolished the activity. Both the γ-phenylpropylamines (e.g., 1-phenyl-3-aminobutane, γ-phenylpropylamine, γ-phenyl-N,N-dimethylpropylamine) and the benzylamines (e.g., α-methylbenzylamine, N,N-diethylbenzylamine, benzylamine) were found to be inactive as releasers of norepinephrine (Daly et al., 1966).
