2-Amino-5-nitrobenzophenone

An approach to shortening the timeframe between the emergence of new compounds on the drugs market and the availability of reference standards: The microscale syntheses of nitrazolam and clonazolam for use as reference materials, utilizing polymer-supported reagents.[Pubmed:29542872]

Drug Test Anal. 2018 Mar 15.

Nitrazolam and clonazolam are 2 designer benzodiazepines available from Internet retailers. There is growing evidence suggesting that such compounds have the potential to cause severe adverse events. Information about tolerability in humans is scarce but typically, low doses can be difficult to administer for users when handling bulk material. Variability of the active ingredient in tablet formulations can also be of a concern. Customs, toxicology and forensic laboratories are increasingly encountering designer benzodiazepines, both in tablet and powdered form. The unavailability of reference standards can impact on the ability to identify these compounds. Therefore, the need arises for exploring in-house approaches to the preparation of new psychoactive substances (NPS) that can be carried out in a timely manner. The present study was triggered when samples of clonazolam were received in powdered and tablet form at a time when reference material for this drug was commercially unavailable. Therefore, microscale syntheses of clonazolam and its deschloro analog nitrazolam were developed utilizing polymer-supported reagents starting from 2-amino-2'-chloro-5-nitrobenzophenone (clonazolam) and 2-Amino-5-nitrobenzophenone (nitrazolam). The final reaction step forming the 1,2,4-triazole ring moiety was performed within a gas chromatography-mass spectrometry (GC-MS) injector. A comparison with a preparative scale synthesis of both benzodiazepine derivatives showed that microscale synthesis might be an attractive option for a forensic laboratory in terms of time and cost savings when compared with traditional methods of synthesis and when qualitative identifications are needed to direct forensic casework. The reaction by-product profiles for both the micro and the preparative scale syntheses are also presented.

Structural features of the 2-amino-5-nitrobenzophenone by means of vibrational spectroscopy HF and DFT, first order hyperpolarizability, NBO, HOMO-LUMO and theromodynamic properties.[Pubmed:24152867]

Spectrochim Acta A Mol Biomol Spectrosc. 2014 Jan 24;118:835-46.

The FT-IR and Raman spectra of 2-Amino-5-nitrobenzophenone (ANBP) molecule have been recorded using Brucker IFS 66 V spectrometer in the range of 4000-100 cm(-1). The molecular geometry and vibrational frequencies in the ground state are calculated using the Hartree-Fock (HF) and B3LYP with 6-311+G(d) basis set. The computed values of frequencies are scaled using a suitable scale factor to yield good coherence with the observed values. The isotropic HF and DFT analysis showed good agreement with experimental observations comparison of the fundamental vibrational frequencies with calculated results by HF and B3LYP methods indicates that B3LYP/6-311+G(d) is superior to HF/6-311+G(d) for molecular vibrational problems. The electric dipole moment (mu) and first hyper polarizability (beta) values of the investigated molecule were computed using density functional theory calculations. Stability of the molecule arising from hyperconjucative interactions leading to its bioactivity, charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The calculated HOMO-LUMO energies shows that charge transfer occur within the molecule. The thermodynamic functions (heat capacity, internal heat energy, Gibbs energy and entropy) from spectroscopic data by statistical methods were obtained for the range of temperature 100-1000 K. The observed and calculated frequencies are found to be in good agreement.

Studies of polymorphism in three compounds by single crystal X-ray diffraction.[Pubmed:10692639]

Int J Pharm. 2000 Jan 25;194(2):147-53.

The role of single crystal diffraction in the quantitative determination of polymorphism is demonstrated by the examination of three compounds. Two polymorphs were found for each of the compounds bis(2-nitrophenyl) trisulphide (1), 2-Amino-5-nitrobenzophenone (2) and bis(2-nitrophenyl) sulphide (3). Only in one polymorph of (1) does molecular symmetry correspond with crystallographic symmetry. In (2) the polymorphs arise in the same crystal class and in the same crystallographic space group whereas in (3) the two polymorphs exist in different crystal classes and hence in different space groups. Crystallographic space group transformation is also discussed.

[The development of mass-screening method for benzodiazepines by radioimmunoassay].[Pubmed:8315856]

Nihon Hoigaku Zasshi. 1993 Feb;47(1):18-28.

For the mass-screening of benzodiazepines in urine, radioimmunoassays (RIAs) for two benzophenones (metabolites of the drugs) were established, and an animal experiment was carried out to verify their usefulness. Immunogens were prepared by condensing 2-hemisuccinyl derivatives of 2-amino-5-chlorobenzophenone (A-CBP) or 2-Amino-5-nitrobenzophenone (A-NBP) to bovine serum albumin (BSA). Antisera were produced in rabbits by immunization with the individual antigens. Two kinds of RIA were established separately for A-CBP and A-NBP using each antiserum, and their sensitivities were 150 pg/tube and 30 pg/tube, respectively. The antisera had broad cross-reactivity with many chlorbenzophenone and nitrobenzophenone derivatives, respectively. Diazepam or nitrazepam was administered to rats, and the total amounts of each in urine (benzodiazepines plus their metabolites such as benzophenones) were determined relative to time using the RIAs after acid hydrolysis of the specimen. The benzophenones were positive in urine even 9 h after administration, whereas diazepam was undetectable using a RIA against diazepam. The characterization of the antisera and the results of the animal experiments indicate that these RIAs will be very useful for mass-screening of benzodiazepines.

Determination of nitrazepam and its main metabolites in urine by thin-layer chromatography and direct densitometry.[Pubmed:4019664]

J Chromatogr. 1985 Apr 12;339(1):163-9.

A method for the direct quantitative densitometry of nitrazepam and its main metabolites (7-aminonitrazepam, 7-acetamidonitrazepam and 2-Amino-5-nitrobenzophenone) in urine was developed. The unchanged drug and its metabolites were extracted with benzene-dichloromethane (4:1), subjected to thin-layer chromatography, and determined by direct ultraviolet densitometry. Recovery experiments showed that the method was quantitative. The limit of detection was 5 ng/ml for 2-Amino-5-nitrobenzophenone and 10 ng/ml for other compounds. The method was applied to the determination of nitrazepam and its metabolites excreted in human urine after administration of 10 mg of the drug.

Effect of temperature and relative humidity on nitrazepam stability in solid state.[Pubmed:874750]

J Pharm Sci. 1977 May;66(5):676-80.

The decomposition of a 1% dilution of nitrazepam in microcrystalline cellulose was established by quantitative determination of the two main breakdown products, 2-Amino-5-nitrobenzophenone and 3-amino-6-nitro-4-phenyl-2(1H)-quinolone, using in situ diffuse reflectance measurements on thin-layer chromatograms. The decomposition and formation rate constant of nitrazepam and of the breakdown products, respectively, were determined at four temperatures and six relative humidities. By means of a three-parameter regression equation, it was possible to correlate quantitatively the decomposition constant of nitrazepam to both temperature and relative humidity.