5958-24-7

Usage

Chemical Properties

White Yellow Solid

Uses

Chlordiazepoxide (C327050) derivative.

InChI:InChI=1/C15H10Cl2N2O/c16-9-14-18-13-7-6-11(17)8-12(13)15(19(14)20)10-4-2-1-3-5-10/h1-8H,9H2

Synthetic route

chloroacetyl chloride (79-04-9) + 2-amino-5-chlorobenzophenone oxime (18097-52-4) → 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7)

Conditions	Yield
In acetic acid at 50℃; for 0.166667h;	74%

2-Amino-5-chlorobenzophenone (719-59-5) → 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89 percent / NH2OH*HCl / aq. ethanol / 10 h / Heating 2: 74 percent / acetic acid / 0.17 h / 50 °C View Scheme

6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) + dimethyl amine (124-40-3) → 6-Chlor-2-(dimethylamino)methyl-4-phenyl-chinazolin-3-oxid (72624-66-9)

Conditions	Yield
In methanol for 72h; Ambient temperature;	97%

6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) → N-Demethylchlordiazepoxide (7722-15-8)

Conditions	Yield
With ammonia In methanol for 72h; Ambient temperature;	96%

6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) + N-methylaniline (100-61-8) → 6-Chlor-2-<(N-methyl)-phenylamino>methyl-4-phenyl-chinazolin-3-oxid

Conditions	Yield
In methanol for 72h; Ambient temperature;	76%

6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) + aniline (62-53-3) → 6-Chlor-4-phenyl-2-(phenylamino)methyl-chinazolin-3-oxid (27424-13-1)

Conditions	Yield
In methanol for 72h; Ambient temperature;	65%

4-(2-AMINOETHYL)MORPHOLINE (2038-03-1) + 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) → (7-chloro-4-oxy-5-phenyl-3H-benzo[e][1,4]diazepin-2-yl)-(2-morpholin-4-yl-ethyl)-amine

4-(3-Aminopropyl)morpholine (123-00-2) + 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) → (7-chloro-4-oxy-5-phenyl-3H-benzo[e][1,4]diazepin-2-yl)-(3-morpholin-4-yl-propyl)-amine

6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) → 6-chloro-2-phenylbenzo[d]oxazole (15952-20-2)

Conditions	Yield
In benzene Irradiation;

6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) → 8-chloro-6-phenyl-1H-benzo[d][1,2,6]oxadiazocin-2-one oxime (30739-32-3)

Conditions	Yield
With potassium chloride; hydroxylamine hydrochloride In ethanol

piperidine (110-89-4) + 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) → 6-Chlor-4-phenyl-2-piperidinomethyl-chinazolin-3-oxid (21804-17-1)

Conditions	Yield
In methanol for 72h; Ambient temperature;	1.74 g

N,N-dimethyl acetamide (127-19-5) + 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) → <7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ylidene>N,N-dimethylacetamide 4-oxide (109774-48-3)

Conditions	Yield
With lithium diisopropyl amide 1) hexane, tetrahydrofuran, below -50 deg C 2) warming to room temperature, 1 h; Yield given. Multistep reaction;

6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) → <7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ylidene>-N,N-dimethylacetamide (109774-49-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) lithium diisopropylamide / 1) hexane, tetrahydrofuran, below -50 deg C 2) warming to room temperature, 1 h 2: PCl3 / CH2Cl2 / 0.5 h View Scheme

6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide (5958-24-7) → 7-chloro-alpha-(hydroxyimino)-N,N-dimethyl-5-phenyl-3H-1,4-benzodiazepine-2-acetamide 4-oxide (109789-71-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) lithium diisopropylamide / 1) hexane, tetrahydrofuran, below -50 deg C 2) warming to room temperature, 1 h 2: 73 percent / sodium nitrite, acetic acid / 1 h View Scheme

Upstream product

• 719-59-5 5-chloro-2-aminobenzophenone 
• 79-04-9 chloroacetyl chloride 
• 18097-52-4 2-amino-5-chlorobenzophenone oxime 

Downstream Products

• 109789-71-1 7-chloro-alpha-(hydroxyimino)-N,N-dimethyl-5-phenyl-3H-1,4-benzodiazepine-2-acetamide 4-oxide 
• 109774-49-4 <7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ylidene>-N,N-dimethylacetamide 
• 30739-32-3 8-chloro-6-phenyl-1H-benzo[d][1,2,6]oxadiazocin-2-one oxime 
• 15952-20-2 6-chloro-2-phenylbenzo[d]oxazole 
• 7722-15-8 N-Demethylchlordiazepoxide 
• 27424-13-1 6-Chlor-4-phenyl-2-(phenylamino)methyl-chinazolin-3-oxid 
• 72624-66-9 6-Chlor-2-(dimethylamino)methyl-4-phenyl-chinazolin-3-oxid 
• 109774-48-3 <7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ylidene>N,N-dimethylacetamide 4-oxide 

Relevant academic research and scientific papers

Mechanism of selective formation of 2-amino-substituted 1,4-benzodiazepin-4-oxides and 2-aminomethyl substituted quinazolin-3-oxides from chloromethyl quinazolin-N-oxides indications from perturbation theory

The o-amino-acetophenone and -benzophenone oximes 1a-c react with chloroacetyl chloride giving the 2-chloromethyl-quinazoline-3-oxides 6a-c. The mechanism is explained using the perturbation theory. With ammonia and N-prim. aliphatic amines, compounds 6a-c yield 1,4-benzodiazepines 16 and 17 as ring-enlarged products, with aromatic and with N-sec. aliphatic amines, quinazoline derivatives 10-13 are formed. The constitution of the heterocycles is proved by nmr spectroscopic methods. Selective formation of the heterocyclic products is explained with the relative thermodynamic stability of the corresponding 2-adducts 14.

Process for preparing 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide and intermediates therefor

A process is described for the preparation of 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide, a key intermediate in the synthesis of the known useful psychotherapeutic agents: chlorodiazepoxide and diazepam. This intermediate is prepared by the cyclization of 2-(1'-chloroimino-2'-chloromethyl)-5-chlorobenzophenone, itself a new compound. This compound in turn is prepared by the chloroacetylation of 2-amino-5-chlorobenzophenone to 2-chloroacetamido-5-chlorobenzophenone, another novel compound, and subsequent iminochloride formation.