Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

1.5- Benzodiazepines oxidation

Lormetazepam (84) is readily synthesized by Polonovski rearrangement of benzodiazepine oxide derivative by heating with acetic anhydride followed by saponification of the resulting rearranged ester.The mechanism of this rearrangement to... [Pg.196]

Benzodiazcpine 4-oxides are also produced from 2-(chloromethyl)-l,2-dihydroquin-azoline 3-oxides 11. Thus, the action of potassium /< )7-butoxide on compound 11a gives the fused aziridine 12a, which readily isomerizes to the 5H-], 4-benzodiazepine 4-oxidc 13a on heating. The homolog lib similarly affords the 5//-benzodiazepine oxide 13b on treatment with potassium rerr-butoxide via the aziridine 12b, which, however, could not be isolated. Under different conditions, i.e. with aqueous ethanolic sodium hydroxide, compound 11b is transformed into the tautomeric 3//-1,4-benzodiazepine 4-oxide 14.222... [Pg.400]

The benzodiazepine oxide 5 is converted into the 3//-1,4-benzodiazepine 6 by catalytic hydrogenation,21 ... [Pg.402]

Greenblatt DJ, Divoll M, Abernethy DR, et al. Antipyrine kinetics in the elderly prediction of age-related changes in benzodiazepine oxidizing capacity. J Pharmacol Exp Ther 1982 220 120-126. [Pg.44]

Diazepam is a benzodiazepine. Diazepam is more reliably absorbed following oral rather than intramuscular admininstration. This may be due to precipitation in the muscle. Diazepam appears to undergo enterohepatic recirculation with a second plasma peak occurring 4-6 hours after initial administration. This may be associated with re-sedation. Diazepam is oxidised in the liver to active metabolites including desmethyldiazepam (nordiazepam), which has a half-life of over 100 hours. Benzodiazepine oxidation may be impaired in patients with liver disease and in some elderly patients. Metabolism of benzodiazepines such as oxazepam and lorazepam is not impaired in the elderly and in those with liver dysfunction. [Pg.89]

Alprazolam, U5P. Alprazolam. 8-chloro-l-methyl-6-phcnyl-4Ay-s-lriazoIo 4.3-oJll.4 bcnzodiazepinc (Xanax), is rapidly absorbed from the GI tract. Protein binding is lower (—70%) than with most benzodiazepines. Oxidative metabolism of the methyl group to the methyl alcohol followed by conjugation is rapid consequently, the duration of action is short. The drug is a highly potent anxiolytic on a milligram basis. [Pg.492]

The main impetus that led to extensive studies of the conversion of quinazolines (e.g., 105) into benzodiazepines (e.g., 106), benzoxadiazepines, benzotriazocines (e.g., 108) and benzoxadiazocines (e.g., 109), and the reverse transformations, has been the wide medicinal usefulness of several benzodiazepines (e.g.. Librium, Valium, Serax) as tranquilizers. The 2-chloro-methylquinazoline 3-oxide 105 reacted with alkylamines in which the alkyl group (e.g., methyl) is small to give the benzodiazepine oxide 106 (R = H ... [Pg.50]

A regiospecific cycloaddition occurs between the benzodiazepine oxide (277) and ap-unsaturated esters,leading to the adduct (278). iV-Acylacetylphenyl-... [Pg.399]

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to... Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...
Azete, trisdimethylamino-isolation, 7, 278 Azetes, 7, 237-284, 278-284 benzo fused, 7, 278 benzodiazepine fused applications, 7, 284 fused ring, 7, 341-362 structure, 7, 360 2,3-naphtho fusion, 7, 278 reactivity, 7, 279 structure, 7, 278 synthesis, 7, 282-283 Azetidine, acylring expansion, 7, 241 synthesis, 7, 246 Azetidine, 3-acyl-irradiation, 7, 239 synthesis, 7, 246 Azetidine, N-acyl-synthesis, 7, 245 Azetidine, alkyl-synthesis, 7, 246 Azetidine, 3-alkylthio-synthesis, 7, 246 Azetidine, 3-amino-synthesis, 7, 246 Azetidine, N-amino-oxidation, 7, 241 synthesis, 7, 246 Azetidine, aryl-synthesis, 7, 246... [Pg.524]

Benzodiazepines as antianxiety agents, 1, 170 as anticonvulsants, 1, 166 organometallic complexes, 7, 604 as sedatives, 1, 166 IH- 1,2-Benzodiazepines conversion to 3H-1,2-benzodiazepines, 7, 604 synthesis, 7, 597, 598, 604 3H-1,2-Benzodiazepines acid-catalyzed reactions, 7, 601 nucleophilic reactions, 7, 604 oxidation, 7, 603 synthesis, 7, 596 thermal reactions, 7, 600 5H-1,2-Benzodiazepines photochemical reactions, 7, 599 synthesis, 7, 603... [Pg.544]

Neither the oxide nor the amidine function are in fact required for activity. Treatment of the oxime, 7, with chloro-acetyl chloride in the presence of sodium hydroxide proceeds directly to the benzodiazepine ring system (14)(the hydroxyl ion presumably fulfills a role analogous to methylamine in the above rearrangement). Reduction of the N-oxide function of 14 leads to diazepam (15). ... [Pg.365]

Chemical Name 7-chloro-N-methyl-5-phenvl-3H-1,4-benzodiazepin-2-amino-4-oxide hydrochloride... [Pg.304]

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. [Pg.305]

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. [Pg.305]

To a stirred suspension of 10 grams (35 mmol) of 7-chloro-5-phenyl-3H-1,4-benzodiazepin-2(1H) one 4-oxide in approximately 150 ml of methanol was added in portions an excess of a solution of diazomethane in ether. After about one hour, almost complete solution had occurred and the reaction mixture was filtered. The filtrate was concentrated in vacuo to a small volume and diluted with ether and petroleum ether. The reaction product, 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2(1 H)-one 4-oxide, crystallized in colorless prisms. The product was filtered off and recrystallized from acetone, MP 188°-189°C. [Pg.466]

A mixture of 3 grams (0.01 mol) of 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2(1 H)-one 4-oxide, 30 ml of chloroform and 1 ml of phosphorus trichloride was refluxed for one hour. The reaction mixture was then poured on ice and stirred with an excess of 40% sodium hydroxide solution. The chloroform was then separated, dried with sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in methylene chloride and crystallized by the addition of petroleum ether. The product, 7-chloro-Tmethyl-5-phenyl-3H-1,4-benzodiazepin-2(1 H)-one, was recrystallized from a mixture of acetone and petroleum ether forming colorless plates melting at 125°-126°C. [Pg.466]

Chloro-1 -dihvdro-5-phenvl-2H-1,4-benzodiazepin-2-one-4-oxide Acetic anhydride Sodium hydroxide... [Pg.1130]

A) Suspend lOg of 7-chloro-l -dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide in 150 ml of acetic anhydride and warm on a steam bath with stirring until all the solid has dissolved. Cool and filter off crystalline, analytically pure 3-acetoxy-7-chloro-1,3-dihydro-5-phenyl-2H-1 /t-benzodiazepin-2-one, melting point 242°C to 243°C. [Pg.1130]

P-Blockers, benzodiazepines, NSAIDs, barbiturates NSAIDs, protease inhibitors, P-blockers, benzodiazepines Antimalarials, NSAIDs, P-blockers, bronchodilators Phosphine oxides, NSAIDs, anticonvulsants Bronchodilators, P-blockers... [Pg.303]

Reduction of the 1//-1,2-benzodiazepines 6 with lithium aluminum hydride results in the dihydro compounds 8, which are dehydrogenated to the 3H-1,2-benzodiazepines 9 by 4-phenyl-4//-l,2,4-triazole-3,5-dione.123 The products readily revert to the 1//-tautomers in the presence of sodium methoxide. 3//-1,2-Benzodiazepines react with 3-chloroperoxybenzoic acid to give mixtures of 1- and 2-oxides, 10 and 11, in which the latter predominate. Treatment of the 2-oxides 11 with nucleophiles provides 3-substituted H- 1.2-benzodiazepines 12. Selected examples are given.124... [Pg.355]

Reactions of 3//-1,2-Benzodiazepine 2-Oxides 11 with Nucleophiles Under Basic Conditions. Preparation of 3-Methoxy-lW-l,2-bcnzodiazepine (12c) Typical Procedure 124... [Pg.357]

The benzodiazepine 2-oxide 11a (0.20 g, 1.25 mmol) in MeOH (5 mL) was treated with NaOMe (0.15 g, large excess) and the mixture was stirred at 20 C for 18 h and evaporated in vacuo. The residue was extracted with CH2C12. The extract was washed with H,0. dried (MgS04) and evaporated and the residue was chromatographed (silica gel, hexane/i-Pr20, 1 1) yield 0.143 g (66%) yellow prisms (i-Pr20) mp 85-86 C. [Pg.357]

H-1,4-Benzodiazepine 4-Oxides by Ring Expansion of 2-(Chloromethy])quinazoiine 3-Oxides... [Pg.399]

Chloromethyl)quinazoline 3-oxides, c.g. 8, react with ammonia and primary amines to yield 3//-1,4-benzodiazepine 4-oxides 10, sometimes accompanied by the simple substitution products 9.219 Dimethylamine220 and pyrrolidine221 react analogously, but other secondary amines afford only products of type 9. [Pg.399]

Chloro-5-phenyl-3i/-l,4-benzodiazepin-2-amine 4-Oxide (10 a) Typical Procedure 219... [Pg.400]

Chloro-3-methyl-5-phenyl-3//-1,4-benzodiazepine 4-Oxide (14) Single Procedure 222... [Pg.401]

Chloro-5-phenvl-l//-l,4-benzodiazepin-2(3//)-one 4-Oxide (I6d) Typical Procedure 223... [Pg.401]

C hloro-5-phenyl-1 /7-1,4-benzodiazepin-2(3f/)-onc 4-oxide (1) is produced by the action of peracetic acid on the corresponding benzodiazepinone.223... [Pg.401]

Chloro-5-(2-fluorophenyl)-l-methyl-2-(methylsulfanyl)-17/-l,4-benzodiazepine (3) is oxidized by 3-chloroperoxybenzoic acid to the corresponding sulfoxide 2 or sulfone 4, depending on the amount of the reagent used.230... [Pg.402]

The benzodiazepine 4-oxide 5 (15 g, 50 mmol) in warm dioxane (200 mL) was cooled to 20 C and hydrogenated at atmospheric pressure in the presence of Raney nickel (20 g). The theoretical volume of hydrogen had been absorbed after 2 h. The precipitated product was dissolved by heating tile mixture and the catalyst was removed by filtration. The product separated yield 14.1 g (99.5%) yellowish plates mp 240-241 C (acetone). [Pg.402]


See other pages where 1.5- Benzodiazepines oxidation is mentioned: [Pg.508]    [Pg.508]    [Pg.544]    [Pg.544]    [Pg.544]    [Pg.679]    [Pg.98]    [Pg.466]    [Pg.356]    [Pg.368]    [Pg.388]    [Pg.401]    [Pg.401]    [Pg.401]    [Pg.402]    [Pg.403]   
See also in sourсe #XX -- [ Pg.17 , Pg.39 ]




SEARCH



3//-l,4-Benzodiazepine 4-oxides

3H-1,4-Benzodiazepine 4-oxides

3H-l,4-Benzodiazepin-2 -one 4-oxides, 2-acylamino

Polonovski reaction benzodiazepine oxide

© 2024 chempedia.info