Dissolve 0.206 moles (50 gr.) 2-amino-5-nitrobenzophenone in 250 mL dry chloroform, add over 5 min. 24 mL (314 mmol) chloroacetyl chloride, stir 2 hrs at 35 °C with moisture protection.
Evaporate all volatiles at the rotary evaporator, add more 100 mL chloroform to the residue and evaporate again to total dryness.
Take up the resultant 2-(chloroacetamido)-5-nitrobenzophenone in 200 mL THF, add 42 g (0.3 moles) Hexamine (hexamethylenetetramine), 900 mL 96% alcohol, and 220 mL (2.95 moles NH3) 25% ammonia solution, density 0.91 kg/L.
Reflux for 6 hrs, evaporate (rest in vacuo at the rotary evaporator) all volatiles, add 240 mL toluene and 1 gr. toluenesulfonic acid hydrate and shake.
Reflux with Dean-Stark adapter/condenser for 90 min., add 150 mL hot water and let cool down over night.
Filter of the brown solid, wash twice with 100 mL water and dissolve in 400 mL dichloromethane.
Pack a 30 mm diameter column 5 cm high with silica gel (F254, Merck) / dichloromethane, filter the solution of the crude product through it.
Wash the column with 100 mL more dichloromethane (the absorptive filtration will remove some tar), and evaporate the complete filtrate to complete dryness.
If I replace 2-amino-5-nitrobenzophenone by 2-amino-5-nitro-2'-fluorobenzophenone Can I then use the same method to produce Flunitrazepam??????
No you can't, althought it might seem possible at first. (but who knows?)
The correct synthesis for 2'-fluoro-5-nitro-benzodiazepine compds. AFAIK goes like follows:
starting from 2-[methyl]amino-2'-fluorobenzophenone, simply condense this with ethylglycinate hydrochloride (glycine ethyl ester HCl salt) to get a [n-methylated] "fluorazepam", then simply nitrate this with HNO3/H2SO4 to yield flunitrazepam.......
(you might want to take a look at patents US3116203, US3123529, US3203990 and FR2529203 too.. )
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