3H-1,4-Benzodiazepine 4-oxides

Ninety-eight grams of 6-chloro-2-chloromethyl-4-phenylquinazoline 3-oxide hydrochloride were introduced into 600 cc of ice cold 25% methanolic methylamine. The mixture was initially cooled to about 30°C and then stirred at room temperature. After 15 hours the reaction product which precipitated was filtered off. The mother liquor was concentrated in vacuo to dryness. The residue was dissolved in methylene chloride, washed with water and dried with sodium sulfate. The methylene chloride solution was concentrated in vacuo and the crystalline residue was boiled with a small amount of acetone to dissolve the more soluble impurities. The mixture was then cooled at 5°C for 10 hours and filtered. The crystalline product, 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide, was recrystallized from ethanol forming light yellow plates, MP 236° to 236.5°C. 

A solution of 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide in an equiv alent amount of methanolic hydrochloric acid was diluted with ether and petroleum ether. 

H-1,4-Benzodiazepine 4-Oxides by Ring Expansion of 2-(Chloromethy])quinazoiine 3-Oxides... 

SYNS CD 2 CDP CHLORDIAZEPOXIDE CHLORIDIAZEPIDE CHLORIDIAZEPOXIDE CHLORODIAZEPOXIDE 7-CHLORO-2-METHYL-AMINO-5-PHENYL-3H-1,4-BENZODIAZEPINE 4-OXIDE... 

CHLORO-2-METHYLAMINO-5-PHENYL-3H-1.4-BENZODIAZEPIN 4-OXIDE 7-CHLORO-N-METHYL-5-PHENYL-3H-l,4-BENZODIAZEPIN-2-AMINE-4-OXIDE... 

Sternbach and coworkers pointed out that the reactions of the 6-chloro-2-chloromethyl-l,2-dihydro-4-phenylquinazoline 3-oxides 11 with a base gives either the 1,3-dihydro-2//-azirino[ 1,2-fl]quinazoline 4-oxides 13 or the 3H-1,4-benzodiazepine 4-oxide 15. In the first step of the reaction the anion 12 is formed by abstraction of a proton from the 1-nitrogen. The intermediate anion 12 can rearrange to the ring-chain tautomer 14. The relative stabilities of the two anions 12 and 14 are assumed to determine whether product 13 or 15 is formed. Thus when R is hydrogen or chloromethyl, the anion 12 is relatively sufficiently stable to allow the formation of the azirino-quinazoline 13. If, however, R is the electron-releasing methyl group, the anion 12 is destabilized and is converted to anion 14, which leads to benzodiazepine 15. The solvent polarity also influences the stability of the anions 12 and 14. In a nonpolar solvent (ether), the 5//-benzodiazepine 16 (R = Me) was obtained, which can be derived from anion 12 (R = Me) via the azirinoquinazoline 13 (R = Me). In a polar solvent (aqueous ethanol), however, the 3H-benzodiazepine 15 derived from anion 14 (R = Me) was the major product. As bases, potassium /er/-butoxide and sodium hydride were used. ... 

H-l,4-Benzodiazepin-2(lH)-ones from 2-acetamino-3H-1,4-benzodiazepine 4-oxides via 3H-l,4-benzodiazepin-2(lH)-one 4-oxides Selective reduction of N-oxides... 

N HCl added at room temp, to a soln. of 7-chloro-2-(N-methylacetamido)-5-phenyl-3H-1,4-benzodiazepine 4-oxide in dioxane, and allowed to stand 14 hrs. at room temp. 7-chloro-5-phenyl-3H-l,4-benzodiazepin-2(lH)-one 4-oxide (Y 89%) dissolved in dioxane, and hydrogenated with Raney-Ni at room temp, and atmospheric pressure until 1 mole of Hg has been absorbed 7-chloro-5-phenyl-3H-l,4-benzodiazepin-2(lH)-one (Y 92%). F. reductions of N-oxides, also with PCI3, s. L. H. Sternbach and E. Reeder, J. Org. Chem. 26, 4936 (1961). 

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