Benzodiazepine hydrolysis products

Chorazepate Chorazepate, 7-chloro-2,3-dihydro-2,2-dihydroxy-5-phenyl-1H-1,4-benzo-diazepin-3-carboxylic acid (5.1.34), which is used in the form of a dipotassium salt, is synthesized by yet another interesting synthetic scheme. 2-Amino-5-chlorobenzonitrile is used as the initial compound, which upon reaction with phenyhnagnesiumbromide is transformed into 2-amino-5-chlorbenzophenone imine (5.1.32). Reacting this with amino-malonic ester gives a heterocyclization product, 7-chloro-l,3-dihydro-3-carbethoxy-5-phenyl-2H-benzodiazepin-2-one (5.1.33), which upon hydrolysis using an alcoholic solution of potassium hydroxide forms a dipotassium salt (5.1.34), chlorazepate [30-32]. 

Amino-ll//-pyrido[2,l-b]quinazolin-ll-one (203) was obtained as a degradation product of 5,ll-dihydro-6//-pyrido[2,3-b][l,4]benzodiazepin-6-one (327, R = H) and pirenzepine (328) by basic and acidic hydrolysis... 

When 2,4-dimethylbenzodiazepine was treated with sodium nitrite in acetic acid, the major products were 2-methylbenzimidazole and 2-acetyl-3-methylquinoxaline the latter product could arise by initial nitrosation at C-3 to form a 3-hydroxyimino derivative that underwent rearrangement and hydrolysis (59JCS1132). Also isolated in low yield was a compound that, on spectroscopic evidence, was assigned the structure l-nitroso-2,4-dimethyl-1 //-benzodiazepine. 

The simple 1,5-benzodiazepine system (207, R = R = H) has been prepared by reaction of 1,3-dibromopropane with the ditosylate of o-phenylenediamine.220,221 This reaction leads to 207 (R = R = tosyl) which can be hydrolyzed directly to 207 (R = R = H).220 Partial hydrolysis of the tosylate led to 207 (R = H, R = tosyl) which on further hydrolysis gave the parent compound.221 In a similar manner the dipotassium salt of o-phenylenediamine ditosylate and 1,3-dibromoacetone gave 208.222 Treatment of 208 with base gave a deep red product for which structure 209 is favored. 

Detection of Benzodiazepines in Urine This test relies on die hydrolysis ofbenzodiazepines or their metabolites to the corresponding amino-benzophenones. The product is extracted, chromatographed, and detected by the formation of an azodye (Bratton Marshall reaction). 

Oxazepam (116) can be converted into a range of 3-(disubstituted-amino) derivatives, in moderate yield, by its reaction with the appropriate 2-amino-4,5-dihydro-l,3,2-dioxaphosphole. A direct route to the 3-amino-derivatives has also been reported.l,3-Dihydro-2//-l,4-benzodiazepin-2-ones react with most isocyanates to give the 1-carbamoyl derivative however, (114), on reaction with trichloroacetyl isocyanate and subsequent hydrolysis, gave the 3-amido-derivative. The latter has been converted into a range of 3-esters.Continuing work on the electrolytic reduction of 2,3-dihydro-l,4-diazepinium salts has shown that the AW-dibenzyl-6-phenyl-compound gives a diazepine dimer and an unexpected rearrangement product, which is 1,4-di-imidazolidinyl-butadiene. ... 

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