Photoelectron spectra of 1,4-benzodiazepines

Photoelectron (PE) spectra of 20 biologically active molecules of 1,4-benzodiazepine derivatives have been measured. The spectra in the range of low ionization energies (IE) were interpreted by comparison of MNDO quantum-chemical calculation data with the perturbation theory estimations. The effect of substituents and structural changes in the series studied is felt mainly by the -MOs of ring A; theortho effect is observed in the PE spectra ofortho isomers.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1583–1587, September, 1993.     

A general procedure for rounding m/z values in low-resolution mass spectra

It was revealed that nominal mass spectra extracted from the same NetCDF file using different gas chromatography/mass spectrometry (GC/MS) software products are not identical. This phenomenon is caused by differences in algorithms used for rounding floating-point m/z values to integers. It was found that all programs under consideration (AMDIS, ChemStation, ChromaTOF, MS Search, OpenChrom) use different procedures. It is necessary to know how fractional parts of accurate m/z values of ions are distributed to determine which algorithm yields more robust results. We estimated the respective distribution using two databases (PubChem and NIST). As a result, we came up with a procedure that minimizes the influence of random errors on rounding to integer m/z values. The procedure we suggest is to sum intensities of all floating-point m/z values in a bin [MZ − 0.38; MZ + 0.62] and assign MZ as a nominal m/z value, where MZ is an integer m/z value.     

The non-aqueous reactions of some 1,4-benzodiazepines.

The data presented for the behavior of 3-hydroxy-1,4-benzodiazepines during non-aqueous titrations indicate that: (a) the First stage protonation during titration as a base with perchloric acid occurs at the N—4 position and is relatively unaffected by substitution at the 3-position, except when the substituent is electron-withdrawing; (b) deprotonation during titration as an acid with tetrabutylammonium hydroxide occurs at the N-1 position rather than at the 3-OH substituent; (c) the similarity of the u.v. spectra of neutral and basic solutions of lorazepam indicate that a tautomerism in basic solution postulated previously does not occur to any great extent; and (d) titration with tetrabutylammonium hydroxide should be acceptable as an assay method tor lorazepam.     

Electron impact and chemical ionization mass spectra of 2,2-diphenyl-3-arylcyclobutanone oximes. Formation of ion m/z 167

The electron impact (EI) and chemical ionization (CI) spectra of 2,2-diphenyl-3-aryl cyclobutanone oximes (1–5) are reported. Formation of diphenylmethyl cation at m/z 167 is a major fragmentation process in both EI and CI spectra. Labelling studies established that the hydrogen involved in this rearrangement transfers from the NOH group and not from cyclobutane ring positions. The [M + 3]⁺ ions are formed under CI conditions as a result of C?N double bond reduction. An interesting secondary kinetic isotope effect is observed in the formation of ion e at m/z 183 in both EI and CI spectra. Other characteristic fragmentation pathways occurring in the EI and CI spectra of these compounds are outlined.     

On the stereospecificity of the structurally diagnostic m/z 84 ion in the mass spectra of gibberellins and kaurenes with a 15-hydroxy substituent

The presence of a 15-hydroxy substituent in naturally-occurring kaurenes and gibberellins gives rise to a structurally diagnostic ion at m/z84 (C₅H₈O) in their electron-impact mass spectra, which shifts to m/z156 for the TMS derivative, and is unaffected by differences in the A and B rings. Studies on a model tricyclic system have shown that this ion is more intense when the stereochemistry of the B/C ring junction is cis than when it is trans. In accordance with a previously proposed pathway for the formation of this ion, deuterium labelling confirms that there is a site-specific transfer of the β-hydrogen from the cis ring junction to the C₅ fragment ion, although a minor modification of the earlier mechanism is proposed.     

Interaction and rearrangement of trimethylsilyloxy functional groups. The structural significance of the m/e 147 ion in the mass spectra of trimethylsil steroidal ethers

Requirements for trimethylsilyloxy group interaction and rearrangement are discussed. It is evident that formation of the m/e 147 ion is a function of the stereochemistry, steric hindrance and separation of the trimethylsilyloxy groups and reflects the stereochemistry of the steroid itself. It is postulated that ring cleavage is not necessarily a prerequisite for the formation of this ion. The occurrence of the m/e 147 ion can be structurally informative in trimethylsilyl derivatives of steroidal alcohols.     

Rapid approach to 3,5-disubstituted 1,4-benzodiazepines via the photo-fries rearrangement of anilides

Different anilides derived from carboxylic acids and substituted anilines have been submitted to the photochemically induced Fries rearrangement giving the corresponding o-amino phenones under conditions that are compatible with the presence of acid-labile groups (such as N-Boc or TBDMSO) on R1 and R3. These compounds, not easily obtained in other ways, are useful building blocks for the preparation of benzocondensated heterocycles. After coupling with N-Boc amino acids and TFA-mediated deprotection, the products cyclized to the corresponding 3,5-disubstituted 1,4-benzodiazepin-2-ones, privileged structures predominantly active in the central nervous system. The same results were obtained by coupling with N-Cbz-protected alpha-amino acids followed by microwave assisted hydrogenolysis. When the Fries rearrangement was carried out on the anilide derived from N-Boc-Ala-OH and the further coupling done with N-Cbz-(OMe)Asp-OH, the formed benzodiazepines could be inserted in a peptide chain for the preparation of conformationally constrained peptidomimetics.     

A novel rearrangement reaction in doubly charged ion mass spectra of acetophenone derivatives

A novel rearrangement reaction for a methyl group is found in doubly charged ion mass spectra of p-substituted acetophenone derivatives. The driving force for the reaction is discussed.     

Negative ion mass spectra of some unsaturated C-glycosides following keV ion bombardment

A series of anomeric unsaturated C-glycosides were studied by negative ion mass spectrometry following keV ion bombardment The compounds bearing an acidic hydrogen show a prominent [M ? H]^? peak; in the other cases, the [M ? H]^? peak is of very low intensity. A retro-Diels–Alder fragmentation and the abstraction of a hydrogen atom from the aglycon residue are observed in all cases.     

1,4-benzodiazepines. Chemistry and some aspects of the structure-activity relationship

Numerous clinically used compounds having favorable tranquilizing and toxic properties possess the 1,4-benzodiazepine skeleton. This group of active substances is readily accessible, e.g. by ring enlargement of quinazoline derivatives, by ring contraction of benzoxadiazocines, and by synthesis from aminobenzophenones, constructing the seven-membered ring in many cases in one step. The relationships between type and position of substituents and the pharmacological properties are illustrated using 1,3-dihydro-5-phenyl-1,4-benzodiazepin-2-ones as examples.     

Emission and absorption spectra of some bridged 1,5-benzodiazepines

Absorption spectra in neutral and acidic media are reported for a series of bridged 1,5-benzodiazepines, which are unable to tautomerize. Comparison is made with non-bridged 1,5-benzodiazepines capable of tautomeric rearrangement. Both bridged and non-bridged 1,5-benzodiazepines are essentially non-fluorescent due to the “proximity effect” of interaction between singlet ηπ* and ππ* states of similar energy, a phenomenon previously recognised in six-membered nitrogen heterocycles.     

Skeletal rearrangement in the mass spectra of tetrasilaadamantanes

The loss of methyl group giving a peak of high intensity is observed in the mass spectra of 1,3,5,7-tetrasilaadamantanes. This skeletal rearrangement must involve the simultaneous rupture of three bonds and concomitant hydrogen transfer. The spectra of the tetrasilaadamantanes are considerably different from the spectrum of adamantane.     

Calibration of mass ranges up to m/z 10,000 in electrospray mass spectrometers

We report that the cesium salts of monobutyl phthalate, heptafluorobutyric acid, tridecafluoroheptanoic acid, and perfluorosebacic acid generate salt/cluster ions that provide calibration peaks for electrospray mass spectrometers. In the case of the cesium salt of tridecafluoroheptanoic acid ions are available up to m/z 10,000.     

Rapid determination of some 1,4-benzodiazepines by flow injection analysis

The rapid determination of three 1,4-benzodiazepines (lorazepam, bromazepam, and chlordiazepoxide) by spectrophotometry has been adapted to flow injection analysis. The effects of flow rate and manifold design on the determination are studied. At sampling rates of 120 samples per hour high reproducibility of measurements (relative standard deviations below 1.5% are obtained with 200-μ1 injection volumes) and low reagent consumtions were achieved. The system was applied to determination of these 1,4-benzodiazepines in pharmaceutical formulations and human urine.     

The mass spectra of some guanidines

The mass spectra of guanidine and ten of its derivatives have been studied under both high and low resolution conditions. Evidence was detected for the migration of methyl groups, the formation of intermediate three-membered ring structures and decompositions involving expulsion of N^. with release of kinetic energy.     

The mass spectra of some chromans

The mass spectra of 4-p-hydroxyphenyl-2,2,4-trimethylchroman and of its thia, selena and sulphonyl analogues are reported and discussed. Formal charge localization on the oxygen atom of the oxo compound is reflected in the production of an abundant [M - 15]⁺ ion. Lack of charge location on the heteroatom of the seleno compound leads to a retro-Diels-Alder reaction. The thio compound exhibits intermediate behaviour, but charge localization on the oxygen atoms is preferred in the sulphone.     

Negative ion mass spectra of some classes of metal carbonyl halides

The negative-ion mass spectra at 70 eV of the compounds Re(CO)₅X (X = Cl, Br, I), Mn(CO)₅X (Br, I), Re₂(CO)₈X₂ (X = Cl, Br, I), Mn₂(CO)₈Br₂ and Rh₂(CO)₄X₂ (X = Cl, Br, I) are reported. The negative molecular ions are absent and the current is mainly transported by fragments due to the loss of carbonyl groups. In the spectra of the bimetallic compounds a rather high intensity is displayed by ionic species containing the two halide substituents. The variations in the ionic abundances are related to the change of the metal-CO bond strength, while the nature of X seems to play a minor role.