Mass spectroscopy of 3-arylpyrimido [ 4 , 5c ] pyridazine-5 , 7 ( 6 H , 8 H )-diones and 3-aryl-7-thioxo-7 , 8-dihydro-6 H-pyrimido [ 4 , 5c ] pyridazine-5-ones : Dimers containing water cluster and quasi-covalent hydrogen bond

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Hydrogen bonding plays a key rule in biology, chemistry and remains a topic of intense current interest as judge by an enormous continuing amount of literatures.A few selected recent articles exemplify the general scope of the topic, ranging from the rule of H-bonding in: weak interaction in the gas phase 8 , supramolecular assembles 9 , helical structure 10 , molecular rotors 11 , through to measurement of H-bond acidity of organic compounds 12 , diastereoselective formation of centrosymmetric 18-membered ring 13 and etc.

Results and Discussion
This paper presents results on the study of mass spectroscopy of 3-arylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones 1a-d and 3-aryl-7-thioxo-7,8-dihydro-6H-pyrimido[4,5-c]pyridazine-5-ones 2a-d.The general formula structures of 1a-d and 2a-d is shown at Scheme 1.All mass fragments of these compounds and their corresponding natural abundances (in parenthesis) are summarized in Table 1.In addition to 1 H NMR data 35 , we found that the mass spectra of these compounds show strongly water clustered in the structure in ratio of 1:1.We assume the monomer and dimer structures of 1a-d and 2a-d as X n (H 2 O) n where, X = heterocyclic compounds 1a-d and 2a-d, n = 1, 2 and thus, the structure of monomer and dimer containing of clustered water will be show as X 1 (H 2 O) 1 and X 2 (H 2 O) 2 , respectively.The mass spectra of these compounds show the both water clustered monomer and dimer forms (Figures 1, 2 and Scheme 2).This observation indicated that there is a strong H-bond between monomer-water and weak H-bond between monomer-monomer species in gas phase.The strong H-bond not only exists between monomer-water species in solution (in DMSO as a suitable solvent) but also in gas phase in ionization chamber.The proposed water clustered dimer forms assigned as I and II structures is shown in Scheme 2. Interestingly, the fragmentation of these compounds in mass ionization chamber show some significant fragments that support the existence of X 1 (H 2 O) 1 and X 2 (H 2 O) 2 (monomer-H 2 O and dimer-2H 2 O species, respectively).
For instance, the proposed fragmentations of 1d and 2d are shown in Scheme 3. The peak of two clustered water ion molecular of dimer (X 2 (H 2 O) 2 ) and monomer (X 1 (H 2 O) 1 ) forms of 1d appeared at m/z 552 ([M + +18] 2 ) in low intensity and at m/z 276 (M + +18) in 50% abundance, respectively.A peak at m/z 259 (M + +1) appeared as base peak (100% abundance) and corresponded to D and/or E fragments.Surprisingly, it seems that some other fragments also show the clustered water molecule and is shown in Scheme 3 and Figures 1 and 2. The X 1 (H 2 O) 1 (B form) was tautomerized to C then converted to D at m/z 259 with lose of water molecule and then captured hydrogen radical.The loss of hydroxyl radical from C can release the E form containing of a water clustered molecule.The capture of hydrogen radical by E was obtained F at m/z 260 (≈ 20%).The release of natural cyanic acid (HCN) from F obtained ion radical G containing of a water molecule at m/z 233 (33%).This form can convert to H then convert to I cation at followed by hydrogen radical loss.The instability of I forced to rearranged to 3-(4-fluorophenyl)oxazolo[4,5-c]pyridazine-6-ium ion (J) at m/z 232.Finally, the hydrogen radical capturing of J produced 3-(4-fluorophenyl)oxazolo [4,5-c]pyridazine (3d) at m/z 233 (33%).In parallel the fragmentation in the mentioned above, the peak at m/z 233 can be rationalized by retro Diels-Alder reaction on X 1 (H 2 O) 1 (B form) formed K involving HNCO loss, then cyclization of this form released β-lactam derivative containing of a clustered water (L).The L can tautomerize to H form (β-lactim).As demonstrates, the water molecule is appeared in many of the fragments and clustered to fragments by strong hydrogen-bonding (Scheme 3).
The fragment of 4-fluorobenzonitrile ion radical at m/z 121 (5d) can also arise from retro-Diels-Alder reaction of 1d and 2d on pyridazine ring moiety (Scheme 3).Fluorobenzene cation at m/z 95 generated from 5d with loss of cyanide radical.Fluorobenzene cation can also generated by heterolytic cleavage of the bond between C3-C9 in 1d and/or 2d molecule.The fragment of the fluorocyclobutadiene cation at m/z 69 generated from fluorobenzene cation with loss of natural acetylene and then loss of acetylene twice produced fluoroacetylene cation at m/z 43.This fragment converted to fluoroacetylene ion radical at m/z 44 by hydrogen radical capturing.
One of important fragmentation on these compounds is the retro-Diels-Alder reaction on pyrimidine ring moiety.This reaction generated the fragment of M with loss of HOCN in 1d and HSCN in 2d and then proton radical capturing produced ion radical of N at m/z 217.The ion radical of diazonium salt derivative (O) at m/z 190 generated from N with loss of neutral cyanic acid (HCN).Finally, the ion radical O generated the fragment of P at m/z 162 with loss of neutral nitrogen gas (N 2 ) (Scheme 3).Another interesting, important and intricate phenomenon in the spectra of 1a-d and 2a-d are the mass of the fragments generated from dimer form containing of two clustered water molecules (X 2 (H 2 O) 2 ).The range of these mass fragments are at 276 < m/z < 552 in 1d and at 292 < m/z < 584 in 2d as representative (Table 1).The fragment of L (m/z 233) can also generate by loss of HNCO and HNCS from 1d and 2d, respectively.The loss of water from L generated the fragment of U at m/z 215.The β-lactam U dimerized to fragment of W at m/z 430.In parallel, fragment of L generated the fragment X at m/z 190 by loss of HNCO.One of the other possible way to obtaining of the m/z 121 (Y) is the loss of water and propiolonitrile molecules from X (Scheme 5).

Table 1 .
Selected mass fragments of 1a-d and 2a-d