Mass Spectra of New Functionally Substituted Heterocycles: V. First Example of McLafferty Rearrangement in the Series of 5-(1-Ethoxyethoxy)-2,3-dihydropyridines and 3-(1-Ethoxyethoxy)pyridines Derived from α-Lithiated 1-(1-Ethoxyethoxy)allene and Methoxymethyl Isothiocyanate

Abstract

Previously unknown 5-(1-ethoxyethoxy)-2-methoxy-6-methylsulfanyl-2,3-dihydropyridine, 3-(1-ethoxyethoxy)-2-methylsulfanylpyridine, and 2-methylsulfanylpyridin-3-ol were synthesized from -lithiated 1-(1-ethoxyethoxy)allene, methoxymethyl isothiocyanate, and methyl iodide, and their fragmentation under electron impact was studied. At ionizing electron energies of 12 and 60 eV in the temperature range from 50 to 250°C, the molecular ions derived from 5-(1-ethoxyethoxy)-2-methoxy-6-methylsulfanyl-2,3-dihydropyridine and 3-(1-ethoxyethoxy)-2-methylsulfanylpyridine decompose along two main pathways: rupture of the C-O bond in the acetal moiety to give oxonium ions with m/z 73 (in the two cases) and 168 (pyridine derivative) and unexpectedly facile McLafferty rearrangement with elimination of ethoxyethene molecule to produce fragment ions with m/z 173 and 141, respectively. The latter pathway was not observed previously for dihydropyridines and acetals, and it predominates in the fragmentation of 3-(1-ethoxyethoxy)-2-methylsulfanylpyridine. Expulsion of methanol molecule from the molecular ion of 5-(1-ethoxyethoxy)-2-methoxy-6-methylsulfanyl-2,3-dihydropyridine occurred only above 170°C. * For communication IV, see [1].Recently reported reactions of metalated alkynes and dienes with heterocumulenes turned out to be a powerful tool in modern syntheses of the most important carbo-and heterocycles [2], including alkylsulfanyl-substituted pyridines [2-5] and still poorly studied 2,3-dihydropyridines [2-6].In continuation of these studies, by reaction of -lithiated 1-(1-ethoxyethoxy)allene with methoxymethyl isothiocyanate we have synthesized with high selectivity previously unknown and inaccessible by other methods 5-(1-ethoxyethoxy)-2-methoxy-6-methylsulfanyl-2,3-dihydropyridine (I). This compound showed an unexpectedly strong tendency to aromatization, leading to 3-(1-ethoxyethoxy)-2-methylsulfanylpyridine (II) [5] which was not described previously as well (Scheme 1). Interestingly, the aromatization process occurred even on storage of dihydropyridine I in a refrigerator, and elimination of ethanol was accelerated not only on heating (~120°C, 1 h) but also in the presence of acid catalysts (HCl, p-toluenesulfonic acid, ~30°C, 1 h). Mild hydrolysis (hydrochloric acid, 20°C, ~10 min) of pyridine II smoothly afforded 2-methylsulfanylpyridin-3-ol (III) [5] which was identified previously (by mass spectrometry) as one of the most important aromatizing components in smoked meat and smoking fluids [7].The presence of labile substituents, 2-methoxy and 5(3)-(1-ethoxyethoxy) groups, in molecules I and II makes these compounds interesting models for both chemical and mass spectrometric studies. It should be emphasized that the known studies on the mass spectra of pyridines were focused mainly on the simplest alkylpyridines [8], while mass spectra of 2,3-dihydropyridines were not reported at all. Moreover, the title

Mass spectra of new heterocycles: IX. Main fragmentaion laws of 7-methyl-2-(methylsulfanyl)-3-(1-ethoxyethoxy)-4,5-dihydro-3H-azepine and its structural isomers (2,3-dihydropyridine, pyrrole, thiophene) under electron impact

“…This is confirmed by the great abundance figure)]. These directions also do not occur in the fragmentation of the molecular ion of 2,3-dihydropyridine XI [14]. Yet in the mass spectrum of, for instance, acetaldehyde diethylacetal the intensity of the peak of the ion [M -Me] + (m/z 103) reaches 14%, here the most abundant peaks are also those with m/z 45 (100%) and 73 (48%) [17].…”

“…Therefore we are first to observe the formation alongside oxonium ions with m/z 73 and 45 two more oxygen-containing ions. Ions [M -OEt] + (m/z 200) and [M -CH(Me)OEt] + (m/z 172) were not also identified in the spectrum of 2,3-dihydropyridine XI [14], the most close in structure to 2,3-dihydropyridine II.…”

“…In contrast to the methoxy-substituted azaanalogs, pyrrole VIII, 2,3-dihydropyridine IX, and 4,5-dihydro-3H-azepine X, where the abundance of the molecular ion peaks attained 100, 50, and 58% respectively [12], compounds I-IV formed a metastable molecular ion with m/z 243 (I rel 1-6%) as was characteristic of aliphatic acetals (mass spectra of these compounds did not contain as a rule the molecular ion peaks) [17] and to a lesser degree, of acetal derivatives of 2,3-dihydropyridinols and pyridinols as we showed recently by the examples of 6-(methylsulfanyl)-2-methoxy-5-(1-ethoxyethoxy)-2,3- [14]. In these cases the intensity of the peaks of the molecular ions amounted to 1-16% (depending on the temperature) and 6-19% respectively.…”

“…In this study in continuation of our systematic research on the mass spectra of new heterocycles [1,[12][13][14][15][16] obtained from allene or acetylene carbanions and isothiocyanates we investigated for the first time and described the behavior of isomeric aza-and thiaheterocycles I-IV at electron impact (70 eV). Like in event of the described in [1,[12][13][14][15][16] heterocycles (thietanes, thiophenes, pyrroles, pyridines, dihydropyridines, azepines, dihydroazepines, etc.)…”

“…Like in event of the described in [1,[12][13][14][15][16] heterocycles (thietanes, thiophenes, pyrroles, pyridines, dihydropyridines, azepines, dihydroazepines, etc.) containing heteroatomic substituents (alkoxy, hydroxy, alkylsulfanyl, amino, imino groups) the molecular ion of compounds I-IV contains several competing centers of the charge and the unpaired electron localization capable of playing and as a rule playing a significant or key role in the processes of the molecular ion fragmentation.…”