2-Amino-5-chlorobenzophenone

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

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
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.010.864 Edit this at Wikidata
EC Number
  • 211-949-7
UNII
  • 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
  • C1=CC=C(C=C1)C(=O)C2=C(C=CC(=C2)Cl)N
Properties
C13H10ClNO
Molar mass 231.68 g·mol−1
Hazards
GHS labelling:[2]
GHS07: Exclamation mark
Warning
H315, H319, H335
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).

Chemistry

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is a substituted derivative of benzophenone, where the hydrogen atom at the 2 position has been replaced by an amino group (-NH2) and the one at the 5 position replaced with a chlorine atom.[1]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

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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.[3]

Synthesis of benzodiazepines

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

Prazepam

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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.[4]

Lorazepam

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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.[5]

Chlordiazepoxide

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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.[6]

References

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  1. ^ a b "2-Amino-5-chlorobenzophenone". pubchem.ncbi.nlm.nih.gov.
  2. ^ "2-Amino-5-chlorobenzophenone". pubchem.ncbi.nlm.nih.gov. Retrieved 16 February 2024.
  3. ^ 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 
  4. ^ Humans, IARC Working Group on the Evaluation of Carcinogenic Risks to (1996), "Prazepam", Some Pharmaceutical Drugs, vol. 66, International Agency for Research on Cancer, pp. 143–155, PMC 7681523, PMID 9097122, retrieved 2024-02-16
  5. ^ "Lorazepam - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-02-16.
  6. ^ "Chlorobenzophenone - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-02-16.