Fragmentation of substituted pyrimido [6,1-a]isoquinolin-2-ones under electron ionization

Abstract

The mass spectral fragmentations of eight substituted pyrimido[6,1-a]isoquinolin-2-ones and four pyrimido[6,1-a]isoquinoline-2,4-diones under electron ionization were examined by metastable ion analysis, a collision-induced dissociation technique and exact mass measurements. The major fragmentation pathways began as radical site-initiated cleavage, and ionization of the nitrogen atom in the isoquinoline ring seemed to prevail. Only the isoquinolinediones gave fragments resulting from ionization of the phenyl ring. Substituents on N3 and C4 had larger effects on the peak intensities than substituents on C6. 2-6 The present work describes a mass spectrometric study of twelve pyrimido[6,1-a]isoquinolines bearing substituents in different positions (Table 1); it forms part of a project relating to investigation of the synthesis, stereochemistry, pharmacology and mass spectrometry of 1,3-oxazino[4,3-a]-and pyrimido[6,1-a]isoquinolines. [4][5][6][7][8][9] The compounds were prepared according to described methods. [8][9][10][11][12][13][14][15] . The fragmentations observed in the 70 eV electron ionization (EI) mass spectra were established by using metastable ion analysis and a collision-induced dissociation (CID) technique. Exact mass measurements were used to confirm the elemental compositions of the ions, but it should be borne in mind that the indicated ion structures are speculative, and merely meant to aid in the visualization of the fragmentation pathways. Our main interest, besides the basic fragmentations of this specific ring system, was focused on the effects of substituents on the fragmentation pathways. A comparison was also made with an earlier study on the mass spectrometric behaviour of 1,3-oxazino[4,3-a]isoquinolines. 7 EXPERIMENTALThe mass spectra were recorded using a Jeol JMS-D300 mass spectrometer (Jeol, Tokyo, Japan) equipped with a combined EI/CI ion source and connected to a Jeol JMA-2000H data system. For all measurements, samples were introduced through a direct inlet at temperatures of 428 to 493 K. Typical source conditions were temperature 433 K, electron energy 70 eV, accelerating voltage 3 kV and ionization current 300 µA. Accurate mass measurements were made for all the compounds by scanning the magnetic field using scan speed 20 s/decade at a resolution of 5000. Perfluorokerosene (PFK) was used as internal reference compound. For some of the compounds, the results were checked by using a Fourier transform ion cyclotron resonance mass spectrometer, Bruker BioApex 47e (Bruker Daltonics, Billerica, USA). The measurements were made in broad band mode (mass range 100-600) with resolution ≥ 30 000. The instrument was calibrated using perfluorotributylamine (PFTBA) as external calibrant. The average precision of the measurements was better than 3 ppm for six measurements. Fragmentation pathways were verified via metastable transitions and/ or CID spectra generated by linked scans at constant B/E. In the CID experiments, helium was added to the first field-free region so that the transmission ...

Selective Gas Adsorption and Unique Structural Topology of a Highly Stable Guest‐Free Zeolite‐Type MOF Material with N‐rich Chiral Open Channels

“…In conformity with the initial site of fragmentation, the types of reaction can be classified into two groups. Ionization occurs on the aromatic ring, as demonstrated in Scheme ( 6a and 7 ), giving rise to the primary ions25 [M–CH 3 ] + and [M–CH 3 O] + , or on the bridgehead N atom (Schemes ). Most new fragmentations were due to the ring N atom and the aromatic part of these molecules.…”

“…Most new fragmentations were due to the ring N atom and the aromatic part of these molecules. In substituted pyrimido[6,1‐ a ]isoquinolin‐2‐ones,25 1,3‐oxazines26–29 and 1,3‐benzoxazines,30 the ionization took place mainly on the N atom in the isoquinoline ring and the direct radical‐site‐initiated cleavages proceeded from there. The molecular ions fragment by losing CH 3 O .…”

Molecular Evolution Using Intramolecular Acyl Migration on myo‐Inositol Benzoates with Thermodynamic and Kinetic Selectors

“…The two most important fragmentation routes of compounds 1 – 4 proved to be (i) loss of the fragments C 8 H, C 8 H 8 , C 8 H and (ii) loss of the whole fused heterocyclic ring system to yield the ion at m/z 191. This ion fragmented further through the loss of a methyl radical giving the ion C 10 H 10 NO at m/z 176 14. Common primary fragmentations for compounds 1 – 10 are given in Scheme .…”

“…Mass spectrometry has been widely applied to the characterization of this class of compounds 12, 13. The mass spectral fragmentation of substituted pyrimido[6,1‐ a ]isoquinolin‐2‐ones14 and oxazino[4,3‐ a ]isoquinolines15 under electron ionization (EI) were studied in detail by the analysis of metastable ions, by the collision‐induced dissociation technique and by exact mass measurements. The EI‐induced fragmentation of N,N ‐ bis (2‐chloroethyl)‐substituted 1,3,2‐oxazaphoshorine‐2‐amine‐2‐oxide and 1,3,2‐oxazaphospholo‐2‐amine‐2‐oxide16 were examined by high‐resolution mass spectrometry and metastable ion analysis 17–19.…”

“…As already mentioned ( vide supra ), the mass spectra of these classes of compounds (especially the cyclophosphamides and hetero‐isoquinoline derivatives)12–22 have previously been studied in detail. Therefore, in the present study, special attention was paid to the influence of the size (five‐ or six‐membered) of the condensed heterocyclic ring moiety, to the effect of changing [4,3‐ a ]‐ to [3,4‐ b ]‐connectivity and to the effect of changing P(O)‐R 1 for SO [R 1 = Ph or N(CH 2 CH 2 Cl) 2 ] substitution on the initial losses in the fragmentation patterns of 1 – 17 .…”