Diazepin-4-ones

Chloromethylpyrimidines such as (281), with bases, undergo ring expansion to 1,3-diazepin-2-ones (284 X = OR, CN, CH(C02Et)2) (77CJC895) via (282) and (283). 

Diazepam. 7-Chloro-l,3 dihydro-l methyN5 phenyl-2H-l,4-benzodiazepin-2-one 7-chloro -1 -methy l-S-phenyl-S/f-IA-benzodiazepin-lOJIfJ-one methyl diazepin-one diacepin La 111 Ro 5-2807 Wy 3467 NSC-77518 Alupram Ansiolin Apauiin Apozcpam Atcnsioc Atilen ... 

Structural isomerization of three-membered rings with exocyclic unsaturation (Scheme 21) has been found with aziridineimines (Section 5.04.3.13) and diaziridineimines (Section 5.08.3.2.4). This involves an acyclic intermediate, while large ring systems prefer to isomerize through bicyclic ones. The 1,2- to 1,3-diazepine conversion is an example (Scheme 22) (Section 5.18.2.2). 

Thieno[ 1,2,3]diazaborines, dihydro-bromination, 1, 656 deuteration, 1, 658 iodination, 1, 656 nitration, 1, 656 nucleophilic substitution copper-promoted, 1, 658 Thienodiazepines synthesis, 7, 595 Thieno[ 1,2]diazepines synthesis, 7, 598 Thieno[2,3-d][l, 2]diazepines synthesis, 4, 749 Thieno[3,2-d][l,2]diazepines synthesis, 4, 749 Thieno[ 1,3]diazepines synthesis, 7, 607 Thieno[ 1,4]diazepinones as anticonvulsants, 1, 170 Thieno[3,4-d][l,3]dioxol-2-one, 4,6-diphenyl-... 

A well-studied case of tautomerism is that of l,2-diazepin-4-ones tautomers 47a and 47b were characterized by NMR, the former being the most stable (85JOC2141). 3,5-Dihydro-4//-2,3-benzodiazepin-4-ones exist as 48a and not as 4-hydroxy tautomers 48b (74JHC401). 

Wentrup s paper [98JCS(P2)2247] contains one of the very few contributions to the tautomerism of functionalized 1,3-diazepines. l,3-Dihydro-l,3-diazepin-2-ones (49a) exist as such and not as hydroxy tautomers 49b ( H and NMR in DMSO solution and IR in the solid state). 

Cyclization of 6-diethylaminohex-3-en-5-yn-2-one (375), an ynaminoketone vinylog, with hydrazine yields 3-diethylamino-7-methyl-5//-l,2-diazepine (375) (97DIS). 

B) Preparation of 7-Chloro-3-Methoxycarbony/-5-Phenyl-2-0xo-2,3-Dihydro-iH-Benzo [fl-1,4-Diazepine (4347 CB) A solution of 9.2 g (0.04 mol) of compound 4356 CB in 20 ml of methanol is added dropwise, in the course of one hour and 30 minutes, to a boiling solution of 9.2 g (0.05 mol) of the hydrochloride of methyl aminomalonate in 30 ml of methanol. When this is completed, heating under reflux is continued for 30 minutes and the product then concentrated to dryness under reduced pressure. The residue is taken up in water and ether, the ethereal layer separated, the product washed with water and dried over sodium sulfate. The solvent is evaporated under reduced pressure. The residue, which consists of the methyl ester, could not be obtained in the crystalline state. It is dissolved in 25 ml of acetic acid, heated under reflux for 15 minutes, the product evaporated to dryness and the residual oil taken up in ether. A colorless solid separates which... 

To a solution of 10 g of 2-N-methyl-aminoacetamido-3-o-chlorobenzoyl-5-ethylthiophene in 50 ml of pyridine are added 20 ml of benzene and 1.9 g of acetic acid. The resulting mixture is refluxed with stirring for 10 hours in a flask provided with a water-removing adaptor. The reaction mixture is concentrated, and the residue is extracted with chloroform. The chloroform layer is washed with water and then with a sodium hydrogen carbonate solution, then dried over magnesium sulfate. The chloroform is distilled off under reduced pressure, and toluene is added to the residue. Thus is precipitated white crystalline-5-o-chloropheny -7-ethyl-1 -methyi-1,2-dihydro-3H-thieno-[2,3-e] [ 1,4] diazepin-2-one, MP 105°C to 106°C. 

Chemical Name 10-[2-(dimethylamino)ethyl] -5,10-dihydro-5-methyl-11H-dibenzo[b,ej-[1,4] diazepin-11-one hydrocliloride... 

Removal of the solvent gave an oil which was taken up In ether and filtered through a pad of Woelm grade I alumina. The eluent was concentrated and the residue was crystallized from methylene chloride/hexane yielding 1-methyl-7-nitro-5-(2-fluorophenyl)-3H-1,4-benzo-diazepin-2(1 H)-one as pale yellow needles melting at 166° to 167°C. 

B) Preparation of 7-Chloro-1,2,3,4-Tetrahydro-1-Methyl-6H-1,4-Bemodiazepin-5-one A mixture of 25.25 g (0.1 mol) of 4-acetyl-7-chloro-1,2,3,4-tetrahydro-1-methyl-5H-1,4-benzo-diazepin-5-one, 33.3 ml (0.1 mol) of 3 N sodium hydroxide and 350 ml of ethanol was heated under reflux for 15 minutes and then concentrated to dryness in vacuo. The residue was treated with 500 ml of water, collected and washed with ethanol to give 20.2 g... 

B) Add to a suspension of 34 g of 3-acetoxy-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzo-diazepin-2-one in 80 ml of alcohol, 6 ml of 4N sodium hydroxide. Allow to stand after complete solution takes place to precipitate a solid. Redissolve the solid by the addition of 80 ml of water. Acidify the solution with acetic acid to give white crystals. Recrystallize from ethanol to obtain 7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1 4-benzodiazepin-2-one, melting point 203°Cto 204°C. 

This reaction can also be used for the synthesis of substituted 1-benzoxepins with one modification instead of the 4/T-benzopyran the 2/7-isomer must be used. 2-[Diazo(phosphoryl)meth-yl]-2//-benzopyrans decompose in the presence of ))3-allylpalladium chloride dimer with elimination of nitrogen to give 1-benzoxepins 2.192 In some cases, the reaction takes a different course and gives 2-methylene-2//-benzopyrans 3.192 In this respect, the bicyclic system behaves differently to the monocyclic diazo(pyranyl)methane. The 2-isomers of the latter structure could not be isolated and gave l//-l,2-diazepines.190 The 4//-benzopyrans do not form benzoxepins but undergo an intramolecular [2+1] cycloaddition to 3,4-dihydro-2,3,4-metheno-2//-ben-... 

The (diazoacetyl)dihydropyrazole 4a is converted into the 1 //-l, 2-diazepin-6(7//)-one 5a in hot acetic acid 73 a somewhat similar reaction affords the diphenyl analog 5b.74... 

An ice-cold solution of diazepinone 5a (1.76 g, 8.8 mmol) in 10% aq K.OH (10 mL, 18 mmol) was treated dropwisc with a solution of dimethyl sulfate (1.4 mL, 11.2 mmol) in MeOH (2mL), whereupon a red solid was precipitated. H20 (10mL) was added and the solid was filtered off, washed with 10% aq MeOH and suspended in MeOH (10 mL). 2M HC1 (15 mL) was added slowly, whereupon the solid dissolved and presently orange crystals of l,5-dimethyl-4-phenyl-l//-1,2-diazepin-6(7//)-one (12) appeared. H20 (10mL) was added and the product was collected yield 0.74g (39%) mp 71-72 C. The filtrate was made alkaline by slowly adding 40% K.OH, whereupon the betaine 13 separated yield 0.76 g (41 %) red plates mp 90-91 C (Et20). 

Aroyl-1 H-1,2-diazepin-3(2//)-ones 27 are obtained80 by demethylation90 of 3-methoxy-l H-1,2-diazepines (vide supra) with chlorotrimethylsilane/sodium iodide. 

The Diels-Alder reaction of cyclopropenes with 1,2,4,5-tetrazines (see Vol.E9c, p 904), a reaction with inverse electron demand, gives isolable 3,4-diazanorcaradienes 1, which are converted into 4H-1,2-diazepines 2 on heating. The transformation involves a symmetry allowed [1,5] sigmatropic shift of one of the bonds of the three-membered ring, a so-called walk rearrangement , followed by valence isomerization.106,107... 

Electrocyclization of certain a,/ y,<5-unsaturated diazo compounds, in which one of the double bonds is embedded in an aromatic ring, affords benzodiazepines. The diazoalkenes 1, produced by heating the sodium salts of the corresponding tosylhydrazoncs, can undergo two kinds of cyclization, [1,5] to yield 3//-pyrazoles, and [1,7] to give diazepines. 

An analogous reaction of (2-acylphenyl)acetic acids with hydrazine or substituted hydrazines in refluxing benzene, xylene or butanol with azeotropic removal of water gives 3//-2,3-benzo-diazepin-4(5//)-ones 3.128,129... 

The bromo derivative 16 reacts with phenylmagnesium bromide in diethyl ether, followed by workup with 5% aqueous hydrobromic acid, to give 2-methyl-4,5-diphenyl-2//-2,3-benzo-diazepin-l(5//)-one (17) in 55% yield.137 No further details were reported. 

The formation of 5//-dibenzo[r/,/][l,3]diazepin-6(7//)-one (13, R = H) in good yield by fusing biphenyl-2,2 -diamine with urea was reported in 1901177 and has since been extended to the preparation of numerous analogs.178 Selected examples are given yields were generally not reported.177-179... 

The 3-methoxy-2//-l,4-diazepines 1 are hydrolyzed to 1/7-1,4-diazepin-2(3//)-ones 2 by hydrochloric acid.160... 

---