The Vespiary

The Hive => Methods Discourse => Topic started by: pHarmacist on November 15, 2002, 06:51:00 PM

Title: Synthesis of benzodiazepines
Post by: pHarmacist on November 15, 2002, 06:51:00 PM

Patent US5466799 (http://l2.espacenet.com/dips/viewer?PN=US5466799&CY=gb&LG=en&DB=EPD)

Abstract
A general method is provided for the synthesis of substituted 2,3-dihydro-5-phenyl-1H-1,4-benzodiazepines by the reaction of bis-trifiated-2,5-dihydroxy benzophenones with 1,2-bisaminoethanes, followed by displacement of the 7-trifloxy group.

...

...Although 5-phenyl-3H-1,4-benzodiazepin-2-(1H)-one can be prepared from 2-aminobenzophenone and glycine ether ester hydrochloride in one step, the synthesis of ring-substituted benzodiazepines requires the use of bis-substituted benzophenones, such as 2-amino-5-chlorobenzophenone, that are both more difficult to obtain and to manipulate. See, for example, U.S. Pat. No. 3,313,815. Thus, a need exists for new syntheses of benzodiazepines that can be readily adapted to the synthesis of a variety of known and novel diazepam analogs...

Dedicated to weedar  ;)

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Title: Pharmacist
Post by: SPISSHAK on November 16, 2002, 11:58:00 PM

I happen to be in pharmacy scholl myself.
But if yu look under the klonazepam synthesis on rhodium's page you will find a preaparation of a 5-nitro, -2- chloro amino benzophenone.
Via a
Freidel crafts reaction between 2-chloro benzoyl choride, and a 4-nitroanaline.

using ZnCl2 as a Lewis acid catalyst.
the yeilds are low I suspect because of side reactions like the formation of an anilide, and multiple frediel crafts alkyltions.
but it's there.
I have a question once you have the bromacetamido chloro, nitro benzophenone, and you react it with hexamethylene tertamine in the presecne of an acid; what is the cycliization mechanism that produces your benzdazopinone?
Cyclization mechanisms can be tricky to decipher.

Title: HMTA cyclization
Post by: Rhodium on November 17, 2002, 12:19:00 AM

Spisshak: It might be found in

https://www.thevespiary.org/rhodium/Rhodium/pdf/benzodiazepine.chemistry.review.pdf (https://www.thevespiary.org/rhodium/Rhodium/pdf/benzodiazepine.chemistry.review.pdf)