Benzodiazepine derivatives carbonylation reactions

For example, the fluorination with [ F]F2 of diazepam, a 1,4-benzodiazepine (Scheme 18), gives the 3-fluoro derivative in up to 60% radiochemical yield [100]. The mechanism proposed is the electrophilic reaction of [ F]F2 with the enol form of the amide (stabilised by conjugation) yielding, after fluorine attachment and reformation of the carbonyl group, the a-fluoroketo derivative. 

Derivatives of 1-methyl-3//-l,4-benzodiazepine-2,5(l/I,4/I)dione (193) were synthesized by ring closure of substituted 2-(A-chloro-acetyl-A-methylaminoJbenzamides with sodium methoxide in methanol.209 Treatment of 193 with lithium aluminum hydride led to reduction of both carbonyl groups.209 The parent tetrahydro system (194) has been prepared by reaction of the tosylate (195) with 1,2-dibromoethane followed by hydrolysis.210 The preparation of 194 by another route had previously been noted.204 Reaction of 194 with formaldehyde or benzaldehyde gave a compound formulated as 196 (R = H or C6H5).210 Hydrolysis of 196 (R = C6H5) with 0.1 N hydrochloric acid gave 194 while 196 (R = H) was not hydrolyzed at this acidity. 

Ring expansion of homophthalic anhydride 114 on reaction with N-i- r-N-methylhydrazine in acetic acid resulted in the 2,3-benzodiazepinedione derivative 115 in moderate yield. The combination of the less hindered nitrogen (NCH3) and the more reactive carbonyl group in 114 may explain the regioselectivity observed. Functionalisation of C5 by the azido group then led ultimately via the amine 116 and the peptide 117 to the 2,3-benzodiazepine-1,4-diones 118. These final compounds were designed to act as peptidomimetics at the carboxy terminus of hydroxyamides one such compound 118 (R =... 

Hydroxyamino)benzodiazepine (90) is acylated on oxygen upon reaction with acid chlorides (acetyl or benzoyl chloride) or isocyanates (methyl isocyanate) in the cold. On heating with acetic anhydride at 100°C, there is an oxido-reductive rearrangement to give the 3-acetoxy-2-methylamino derivative (91) (Scheme 14). This is considered to proceed by isomerization of the nitronium ion formed by cleavage of the N—O bond to the 3-carbonium ion which is trapped by the nucleophile (acetate) <80AP(313)926>. A similar mechanism is used to explain the formation of the 3-(l-imidazolyl) derivative (92) on reaction of (90) with carbonyl diimidazole. 

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