2-Amino-5-chlorobenzophenone

2-Amino-5-chlorobenzophenone ^[1]

Names
IUPAC name (2-Amino-5-chlorophenyl)phenylmethanone
Other names 2-amino-5-chlorobenzophenone 2-Benzoyl-4-chloroaniline (2-amino-5-chlorophenyl)(phenyl)methanone
Identifiers
CAS Number	719-59-5  Y
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL1417425
ChemSpider	12339
ECHA InfoCard	100.010.864
EC Number	211-949-7
PubChem CID	12870
UNII	FR80014ZBT
CompTox Dashboard (EPA)	DTXSID0052463
InChI InChI=1S/C13H10ClNO/c14-10-6-7-12(15)11(8-10)13(16)9-4-2-1-3-5-9/h1-8H,15H2 Key: ZUWXHHBROGLWNH-UHFFFAOYSA-N
SMILES C1=CC=C(C=C1)C(=O)C2=C(C=CC(=C2)Cl)N
Properties
Chemical formula	C13H10ClNO
Molar mass	231.68 g·mol−1
Hazards
GHS labelling: [1]
Pictograms
Signal word	Warning
Hazard statements	H315, H319, H335
Precautionary statements	P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

2-Amino-5-chlorobenzophenone is a substituted benzophenone that can be used in the synthesis of benzodiazepines.

Chemistry

2-Amino-5-chlorobenzophenone is a substituted derivative of benzophenone, where the hydrogen atom at the 2 position has been replaced by an amino group (-NH₂) and the one at the 5 position replaced with a chlorine atom. ^[1]

Synthesis

Among other methods, 2-amino-5-chlorobenzophenone can be synthesized by reducing isoxazole through iron powder. This process also involves using toluene and muriatic acid. ^[2]

Synthesis of benzodiazepines

2-Amino-5-chlorobenzophenone and its derivatives can be used to produce benzodiazepines, a few examples are listed below;

Prazepam

Prazepam can be produced by the acylation of 2-amino-5-chlorobenzophenone with cyclo-propanecarbonyl chloride and triethylamine, 2-cyclopropylmethylamino-5-chlorobenzhydrol is then obtained by using lithium aluminium hydride as a reducing agent, this product is then oxidized by using manganese dioxide. The resulting compound goes another acylation reaction using phthalimidoacetyl chloride and finally treated with hydrazine hydrate to produce prazepam. ^[3]

Lorazepam

Lorazepam can be made using 2-amino-2′,5-dichlorobenzophenone (a derivative of 2-amino-5-chlorobenzophenone), which is first reacted with hydroxylamine, the obtained product is then reacted with chloroacetyl chloride to give 6-chloro-2-chlormethyl-4-(2′-chlorophenyl)quinazolin-3-oxide, a reaction with methylamine produces ring expansion and rearrangement, which forms 7-chloro-2-methylamino-5-(2′-chlorphenyl)-3H-1,4-benzodiazepin-4-oxide, acetylation with acetic anhydride gives a product which goes under hydrolysis by reacting it with hydrochloric acid, this gives 7-chloro-5-(2′-chlorophenyl)-1,2-dihydro-3H-1,4-benzodiazepin-2-on-4-oxide, a second reaction with acetic anhydride gives 7-chloro-1,3-dihydro-3-acetoxy-5-(2′-chlorphenyl)-2H-benzodiazepin-2-one, the last step involves hydrolysis of this product under sodium hydroxide to give lorazepam. ^[4]

Chlordiazepoxide

To make chlordiazepoxide, 2-amino-5-chlorobenzophenone is first reacted with hydroxylamine, the resulting product is then reacted with chloracetyl chloride in acetic acid, resulting in 6-chloro-2-chloromethyl-4-phenylquinazolin-3-oxide, reaction with methylamine gives chlordiazepoxide. ^[4]

References

1. 2-Amino-5-chlorobenzophenone from PubChem
2. CN104230727A,刘为焱; 潘明& 黄雄,"Synthesis technology for producing 2-amino-5-chlorobenzophenone by reducing isoxazole through iron powder",issued 2014-12-24 
3. "Prazepam". Some Pharmaceutical Drugs. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 66. 1996. pp. 143–155. ISBN   978-92-832-1266-9. PMC   7681523 . PMID   9097122.
4. Vardanyan, R.S.; Hruby, V.J. (2006). "Anxiolytics (Tranquilizers)". Synthesis of Essential Drugs. pp. 69–82. doi:10.1016/B978-044452166-8/50005-4. ISBN   978-0-444-52166-8.