New synthesis of diazepam

Abstract

An efficient preparation of 7-chloro-l-methyl-3,4-dihydro-lfl-l,4-benzodiazepine-2,5-dione from 5-chloro-jVmethylisatoic anhydride and glycine has been devised, and from it, by the action of phenylmagnesium chloride on its N-acetyl derivative followed by treatment with hydroxylamine and cleavage of the resulting desacetyl oxime with sodium bisulfite, diazepam has been synthesized. The overall yield is about 50% from 5-chloroisatoic anhydride.

Prescribed drugs containing nitrogen heterocycles: an overview

“…The latter is then hydrolyzed in an acidic medium, affording 2-methylamino-5chlorobenzophenone 529 that is subjected to cyclocondensation via reaction with ethyl ester of glycine hydrochloride to afford the desired diazepam 526 (Scheme 73). [536][537][538][539][540] Lorazepam 536, is also a benzodiazepine medicine. It is prescribed to treat anxiety disorders, trouble sleeping, active seizures including status epilepticus, alcohol withdrawal syndrome, and chemotherapy-induced nausea and vomiting.…”

The effect of metal chelate complexation on the reactivity and absorption spectra of 1,2-naphthoquinones: new types of near-infrared-absorbing metal complex dyes

“…Figure 2 shows that a maximum appears at [ligand]/([ligand] + [Metal]) 0.5 and 0.67, suggesting the formation of 1:l and 1:2 metal@)-ligand complexes in the solution, respectively. In Table 2, the spectral data of the free ligands, (k), (4b), and (7), and their metal complexes in 99% ethanol are summarized. In the cases of ligands (2) and ( 7) the maximum and constant absorbance were obtained in the molar ratio range [metal ion]/[(2c)] 1.2-2.0 and [metal ion]/[(7)] 2.0-4.0, while for (4b) the constant absorbance was obtained for [metal ion]/[(4b)] 100-120.…”

“…Among the three types of compound, (7) was found to be the most suitable ligand for the synthesis of near-IR-absorbing dyes, since it has a good ability to form a metal chelate, and a drastic spectral change is induced upon chelate complexation. As the ratio of molecular extinction coefficient (Re) increased 4.2-4.3 times in comparison with that of the free ligand (7), the resulting metal( 11)- (7) complexes have an intense absorption band in the near-IR region. The absorption maximum [h,,,(complex)] is controllable by changing the metal ion participating in the chelate complexation.…”

A facial synthesis of quinazolino[1,4]benzodiazepine alkaloids via reductive N-heterocyclization of N-(2-nitrobenzoyl)amides: total synthesis of asperlicin C, circumdatin H, and its analogues

“…Benzodiazepines 4a-d were readily prepared in excellent yields through the condensation of isatoic anhydride 3 with the appropriate L-amino acids in aqueous solution in the presence of triethylamine followed by cyclization in refluxing glacial acetic acid. 44,45 Benzodiazepine 4e was prepared in good overall yield by the coupling of glutamic acid with isatoic anhydride 3 50 followed by esterfication and subsequent cyclization of Benzoylation of proline-based 1,4-benzodiazepin-2,5-dione 4a [46][47][48][49] with freshly prepared 2-nitrobenzoyl chloride in the presence of DMAP and Et 3 N in dry CH 2 Cl 2 was used for optimization study. Monitoring the crude reaction mixture by TLC indicated the clean and complete conversion of 4a to the corresponding nitro derivative 6 within 3 hrs.…”