Naphthyridine chemistry. VIII. The mass spectra of the 1,X-naphthyridines and some of their methyl derivatives

The mass spectra of the four parent 1,X-naphthyridines, the 2,3 and 4-monomethyl-1,5-,1,6-. and 1,8- naphthyridincs, seven dimethyl-1,8-naphthyridines, and one trimethyl-1,8-naphthyridine are reported. Evidence for an azatropylium ion intermediate in the fragmentation of the methyl compounds is presented. The fragmentation modes of the naphthyridines are similar to those for the quinolines in addition to several new processes     

Amination of 3,6-dinitro-1,8-naphthyridines

Treatment of 2-amino-3,6-dinitro-1,8-naphthyridines with liquid ammonia/potassium permanganate gives 2,4-diamino-3,6-dinitro-1,8-naphthyridine. From 2-ethoxy-3,6-dinitro-1,8-naphthyridine a mixture of 4-amino-and 5-amino-3,6-dinitro-1,8-naphthyridine was obtained. 2-Chloro-3,6-dinitro-1,8-naphthyridine afforded a mixture of four compounds i. e. 2,4- and 2,5-diamino-3,6-dinitro-1,8-naphthyridine and 2-chloro-5-amino-3,6-dinitro-1,8-naphthyridine and 2-amino-3,6-dinitro-1,8-naphthyridine. A study on covalent amination has shown that 4-amino-2-ethoxy-3,6-dinitro-1,8-naphthyridine undergoes covalent amination at C-5, whereupon in this adduct amino-deethoxylation takes place. In a similar way, 2-chloro- and 2-ethoxy-5-amino-3,6-dinitro-1,8-naphthyridine give covalent amination at C-4.     

1,5-naphthyridines and their N-oxides

The N-oxidation reactions of 2-hydroxy- and 2-amino-1,5-naphthyridines were investigated. 2-Hydroxy-1,5-naphthyridine 5-oxide and 2-hydroxy-, 2-amino-, and 2-acetamido-1,5-naphthyridine 1,5-dioxides were obtained. The structures of the compounds obtained were proved by means of IR and PMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1237–1240, September, 1972.     

Synthesis and properties of 4-substituted 1,5-naphthyridines and their N-oxides

4-Substituted 1,5-naphthyridines and their N-oxides were synthesized, and their structures and properties were studied. The IR and UV spectra of 4-hydroxy- and 4-methoxy-1,5-naphthyridines and their 1-oxides and 1-ethyl-4-oxo-1,4-dihydro-1,5-naphthyridine were examined. It is shown that 4-hydroxy-1,5-naphthyridine and its 1-oxide exist in the crystalline state in the lactam form. A quantitative estimate of the position of the tautomeric equilibrium of 4-hydroxy-1,5-naphthyridine as a function of the polarity of the solvent is given, and the tautomeric equilibrium constants and the percentages of the lactim form are calculated. The basicity constants of 4-chloro-, 4-methoxy-, 4-hydrazino-, 4-methylthio-, 4-acetamido-, and 4-amino-1,5-naphthyridines were measured. A comparison of the calculated and experimental pK_a data provides evidence in favor of the fact that the compounds are protonated at the N₁ atom. A correlation of the basicity constants with the substituent constants is examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 792–799, June, 1981.     

2-(<Emphasis Type="Italic">N</Emphasis>-Phosphorylamino)-substituted 1,8-naphthyridines. synthesis and structure

The previously unknown 2-(N-phosphorylamino)-substituted 1,8-naphthyridines were synthesized by the direct phosphorylation of 2-amino-5,7-dimethyl-1,8-naphthyridine with phosphoryl chlorides of different structures. The structures of the reaction products were confirmed by mass spectrometry, ¹H and ³¹P NMR spectroscopy, and X-ray diffraction study (for one of the compounds).     

Covalent amination of 3,6-dinitro-1,8-naphthyridines

The preparation of 3,6-dinitro-2-R-1,8-naphthyridines ( 1 , R = OH, NH₂, OC₂H₅, Cl) is described and their addition patterns with liquid ammonia are studied. Compound 1 (R = OH, NH₂) gives with liquid ammonia at - 45° as well as at room temperature formation of the covalent ó-adduct 4-amino-1,4-dihydro-3,6-dinitro-2-R-1,8-naphthyridine ( 2 , R = OH, NH₂). Compound 1 (R = OC₂H₅) yields with ammonia at - 45° two σ-adducts, i.e. the C-4 adduct ( 2 , R = OC₂H₅) and the C-5 adduct 5-amino-5,8-dihydro-3,6-dinitro-2-R-1,8-naphthyridine ( 3 , R = OC₂H₅). The ratio is about 50:50. This ratio depends on the temperature; at room temperature the C-5 adduct is more favoured. After staying overnight the ethoxy group has been exchanged for the amino group, yielding 2 (R = NH₂). With 1 (R = Cl) both adducts 2 (R = CI) and 3 (R = CI) were formed, the C-4 adduct 2 (R = CI) is more favoured at room temperature. Prolonged treatment with liquid ammonia leads to an exchange of the chloro atom by the amino group, yielding 2 (R = NH₂).     

Mass spectral fragmentation pattern of 4,4′-bipyridines. Part II. 4,4′-oxybispyridine and 4,4′-thiobispyridine

The mass spectra of 4,4′-oxybispyridine and 4,4′-thiobispyridine are reported. In the former the base peak is due to the molecular ion and the fragmentation routes involve loss of H, CO, HCN, C₂H₂N and C_sHO from the molecular ion as well as rupture of the central bonds. In the latter the base peak is also due to the molecular ion and the fragmentation routes involve loss of H, CS, S, HCN and C₂HS as well as central bond rupture.     

Substituent and H/D randomization in the mass spectra of substituted diphenylacetylenic compounds

The mass spectra of several substituted diphenylacetylenes are reported and the [metastable ion]/[daughter ion] ratios for the isomeric chloro- and bromodiphenylacetylenes suggested substituent scrambling in their respective molecular ions. The metastable ion data also indicated equilibration of the chloro substituents in a series of isomeric dichlorodiphenylacetylenes. In addition, the fragmentation patterns for the amino- and nitrodiphenylacetylenes differed somewhat from most other aromatic amino and nitro compounds. The aminodiphenylacetylenes fragment with expulsion of H₂CN from the molecular ion and the expulsion of HCN from the [M – 1]⁺ ion was only a relatively minor reaction. 4-Nitrodiphenylacetylene loses NO from the molecular ion and OH from the [M – NO]⁺˙, whereas the more familiar loss of OH from the molecular ion was not observed. The mass spectra of several deuterated substituted diphenylacetylenes clearly showed extensive (but not complete) H/D equilibration in the molecular ion or some subsequent decomposition ion. Comparative studies between 4-chloro and 4-bromo substituted biphenyl, diphenylacetylene and diphenyldiacetylene indicated similar degrees of H/D randomization, and the results showed that the ? C?C? group did not inhibit the proton equilibration between the two phenyl groups.     

Proximity effects in the mass spectra of crowded bis(dimethylamino)arenes: Part II—Rearrangements of the molecular radical cations of ‘proton sponges’ by reciprocal methyl/hydrogen transfer

The EI induced fragmentation pathways of 4,5-bis(dimethylamino)fluorene, 4-(d₆-dimethylamino)-5-(dimethylamino)fluorene, 4,5-bis(d₆-dimethylamino)fluorene, 4-(dimethylamino)-5-methylaminofluorene, 4,5-bis-(methylamino)fluorene, 4-amino-5-methylaminofluorene, 1,8-bis(dimethylamino)naphthalene, 1,8-bis(d₆-dimethyl-amino)-naphthalene and 1,8-bis(dimethylamino)-2,7-dimethoxynaphthalene were investigated. A mechanism is pro-posed for the surprising elimination of CH₃? NH₂ from the molecular ion, followed by loss of C₂H₅·, C₂H₄ and CH₃CN and for the accompanying cyclizations to stable heterocyclic ions: prior to fragmentation the molecular radical ion rearranges to new, distonic radical ions by reciprocal H and CH₃ transfers between the adjacent dimethylamino groups. Each of these new, isomeric molecular ions decomposes subsequently in a characteristic way.     

Bridgehead nitrogen heterocycles—II: The mass spectra of some pyrazolo[1,5-a]pyridines

Pyrazolo[1,5-a]pyridine undergoes fragmentation upon electron-impact by loss of HCN or C₂H₂N·. In the 2,3-dimethyl derivative loss of HCN and CH₃CN were both observed from the [M – 1]⁺ ion and, in the 3-methyl-2-phenyl derivative, loss of PhCN occurred from the corresponding [M – 1]⁺ ion. Loss of methyl and phenyl radicals was also observed. In 3-acetyl-2-methyl and 3-benzoyl-2-phenyl derivatives, characteristic losses of the CH₃CO· and PhCO· groups were noted. The introduction of a 7-methyl substituent into the six-membered ring had little effect on the fragmentation pattern.     

Mass spectrometry of 4-amino-4′-nitroazobenzene compounds

The mass spectra of 32 substituted 4-amino-4′-nitroazobenzene compounds have been recorded and the most intense peaks have been used to characterize these spectra. It was found that the spectra of 4-amino-4′-nitroazobenzene compounds are characterized by peaks due to: (1) molecular ions, (2) fragment ions formed by cleavage of one of the carbon-nitrogen bonds adjacent to the azo linkage with the positive charge remaining with the amine fragment, (3) ions formed by cleavage alpha to the amine nitrogen with the charge remaining with the amine substituent, (4) ions formed by cleavage beta to the amine nitrogen with the loss of the amine substituent fragment, (5) secondary ions formed by cleavage beta to the amine nitrogen with the loss of the amine substituent fragment from the primary amine fragment (2), and (6) ions formed by loss of NO from the molecular ion. This work shows that 4-amino-4′-nitroazobenzene compounds exhibit fragmentation which is dependent in a consistent manner on the types of substituents. This work provides a basis for a systematic approach to the identification of 4-amino-4′-nitroazobenzene compounds.     

On the amination of 3-nitro-1,8-naphthyridines

A number of 3-nitro-2-X-1,8-naphthyridines (X = H,Cl,NH₂,OE_t) were successfully aminated into the corresponding 4-amino-3-nitro-2-X-naphthyridines, using liquid ammonia and potassium permanganate as reagents. 4-Amino-1,4-dihydro-3-nitro-2-X-1,8-naphthyridines are the actual species being oxidized by the potassium permanganate; their existence has been by ¹H nmr spectroscopy.     

Mass spectra of some syn- and anti-aromatic aldoximes

The mass spectra of eight pairs of geometric isomers of aromatic oximes and four other single aromatic oximes are reported. The loss of H₂O, HO and HCN are major fragmentations from the molecular ion of all the benzaldoximes studies; however, the loss of HCN from the molecular ion did not occur in the oximes of 9-phenanthraldehyde, 1-naphthaldehyde and 2-naphthaldehyde. The halogen substituted benzaldoximes eliminate HCNO and H₂CNO forming an additional fragmentation pathway from the molecular ion. In general, variations were found for each pair of syn- and anti-oximes but no consistent patterns could be found in the spectra for all the syn-isomers versus all of the anti-isomers. The geometric isomerism of four oximes previously reported in the literature have been established for the first time as anti-m-bromobenzaldoxime, syn-9-phenanthraldoxime, syn-1-naphthaldoxime and syn-2-naphthaldoxime. Three new oxime acetates were prepared and their mass spectra are discussed.     

Pd-catalyzed amidation of 2-chloro- and 2,7-dichloro-1,8-naphthyridines

[reactions: see text] The catalytic amidation between 2-chloro- and 2,7-dichloro-1,8-naphthyridines and primary amides bearing functional groups is reported. When Pd(OAc)2, xantphos, and K2CO3 are used, it is possible to obtain symmetric as well as nonsymmetric 2,7-diamido-1,8-naphthyridines in 50-90% yield with good functional-group tolerance. Monoamidation of 2,7-dichloro-1,8-naphthyridine using 0.9 equiv of the amide proceeded with good selectivity compared to the formation of the diamide, but as a result of the difficult isolation of the product, isolated yields were poor to moderate (22-42%).     

Synthesis of 2– and 4-amino-1,5-naphthyridines

The structure of the product obtained from the reaction of potassium amide in liquid ammonia on 1,5-naphthyridine has been identified as 4-amino-1,5-naphthyridine by comparison with a known sample. The 2-amino isomer was not detected in the mixture. The NMR spectra for 2-and 4-amino-1,5-naphthyridine along with the corresponding chloroisomers are described.     

Mass spectrometry and structure of ions of heterocyclic compounds activated by collision: Naphthiridines and benzazines

The dissociation and the structure at the isomeric [M — HCN]⁺ and [M — 2HCN]⁺ ions, formed during the fragmentation of naphthiridines and benzazines, were investigated by the collisionally activated dissociation (CAD) method. It was established that the stable [M — HCN]⁺ ions of 1,5- and 1,8-naphthiridines, 1,6-naphthiridine, quinoxaline, and quinazoline have different structures. The [M — 2HCN]⁺ ions can exist in two isomeric forms, one of which is characteristic of naphthiridines and the other of benzazines.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vo. 25, No. 5, pp. 626–629, September–October, 1989.     

The electron-impact-induced fragmentation of acridine

Studies of both high and low resolution spectra, and of metastable decompositions occurring in both the first and second field-free regions of the mass spectrometer have led to a postulated scheme for the fragmentation of acridine under electron-impact. There is no specific loss of label from either [9-²H₁]acridine or [4,5-²H₂]acridine in any fragmentation, nor is there any total scrambling of label in either molecular ion prior to loss of HCN. There is certainly some degree of scrambling preceding HCN loss from [M]⁺˙ at 70 eV, but this does not involve the 9-H to any detectable extent. There is no strong evidence for the acridine molecular ion having the same structure as that of four other C₁₃H₉N isomers.     

Massenspektrometrische Fragmentieungen Aomatischer Isocyanide

The mass spectra of 19 aromatic isocyanides are reported and discussed. The main feature of the fragmentation of these compounds is loss of HCN usually indicated by a metastable peak. Although this process is characteristic of the behaviour of aromatic isocyanides the extent to which it dominates the mass spectrum of any aromatic isocyanide is determined by the relative ease of cleavage of other bonds within the molecule. 2,4,6-d₃-phenylisocyanide (Ib) loses predominantly DCN from the molecular ion while 2,4-d₂-1-naphthylisocyanide (lIIb) eliminates HCN. It is therefore concluded that the loss of HCN from aromatic isocyanides is mainly a non-random process (no randomization prior to fragmentation).     

Mass spectral fragmentation pattern of 2,2′-bipyridyls. Part VIII. 2,2′-Bipyridyl-5-carboxylic Acid and 2,2′-bipyridyl-5-sulphonic acid

The mass spectra of 2,2′-bipyridyl-5-carboxylic acid and 2,2′-bipyridyl-5-sulphonic acid obtained by electron impact are described. The principal initial fragmentation routes from the molecular ion of the carboxylic acid involve loss of CO, CN^˙, HCN, CO₂, OH^˙ and H₂O. From the molecular ion of the sulphonic acid the principal fragmentations are accompanied by loss of HCN, O₃, SO₂ and SO₃.     

Electron impact ionization mass spectrometry and tandem mass spectrometry of phenylalkylpyridazines

The mass spectrometric fragmentation behaviour of pyridazine and four monosubstituted derivatives containing a pbenylalkyl side-chain (3- and 4-benizylpyridazine, 3- and 4-(2-pbenylethyl)pyridazine) was investigated. In the electron impact ionization mess spectra of the 3-substituted compounds abundant [M – H]⁺ peaks are observed. This allows a clear distinction between 3- and 4-substituted pyridazines, as the spectra of the latter isomers show only very weak [M – H]⁺ signals. The stability of [M – H]⁺ ions derived from 3-alkylpyridazines (deduced from only the very low abundance of further fragment ions) gives strong evidence for a cyclic structure of these ions. One fragmentation pathway typical of the parent pyridazine, the [M - N₂] fragmentation, was not detectable with any of the phenylalkylpyridazines investigated. Instead, loss of HCN, H₃CN⁺ and N²H⁺ was observed. An interesting fragmentation, observed with 3-(2-phenylethyl)pyridazine, is the loss of ⁺CH₃ from the molecular ion and also from the [M – H]⁺ ion.