Morpholine migration

Flash vacuum pyrolysis (FVP) of the 3-(iV-(pyrimidin-2-yl)imino-l-morpholino)propanoate 179 led to pyrimido-pytimidines 182 and 184, as a result of competition between thermal loss of ethanol or morpholine. The ketenimine 181, being unable to undergo cyclization, underwent [l,3]-ethoxy migration to form 183, leading to 184 (Scheme 28). The ratio of the products was studied on variation of the temperature (400, 530, and 600 °C) and the nature of the amino substiuent (NR1R2 = morpholino, pyrrolidino, N(Me)Ph ) <2004AJC577>. 

Its chemical structure does not allow elimination of HNO, thus supporting the oxidative pathway of activation to NO, a mechanism still possible in this blocked SIN-1A derivative. The final product of the NO-release was found to be l-amino-2-cyanomorpholine (110) [106]. Its formation can be rationalized assuming that, after the oxidative NO-release, deprotonation occurs at the a-position of the morpholine, followed by migration of the cyano group and hydrolytic cleavage of the hydrazone moiety. 

Migration of nitrosamines into consumer products can occur via direct contact of materials such as waxed containers, elastic and rubber etc.81. Morpholine is used extensively as an industrial solvent for wax formulations. The wax formulations are used for coating fruits and vegetables to prevent moisture loss and increase shelf-life of the products. Paper and cardboard packed with morpholine was also found to give rise to NDMA, as these packaging materials were found to be contaminated with NDMA as well. Besides this, rubber products also provided a migratory source for both nitrosamines and nitros-able amine precursors, as trace levels of NDEA and TV-nitrosodibutylamine (NDBA) have been reported in cured meats with amine-based accelerators in the rubber nettings82. 

Further direct evidence for orientation by chemoreception was provided by tagging fish from the above experiment with ultrasonic transmitters, and charting the reaction of treatment and control fish to plumes of morpholine in open lake waters (Scholz 1980). Morpholine imprinted fish always stopped swimming when they encountered a morpholine plume, and remained until it dissipated (0.5-0.4 h) they never stopped for plumes of other chemicals (PEA). In contrast, fish never exposed to morpholine (control) swam directly through plumes of morpholine without stopping (Scholz 1980). The author concluded that morpholine was responsible for guiding the migration of fish imprinted with this chemical to the morpholine scented stream. 

Treatment of [ C]methyl aryl ketones with thaUium(lll) nitrate in acidic methanol (McKillop rearrangement) or with ammonium polysulfide or sulfur and morpholine at elevated temperatures (Willgerodt-Kindler reaction) provides labeled arylacetic acid derivatives. In the first case the aryl group migrates from the carbonyl position into the former methyl position, so that the label is shifted by one position. For example (Figure 6.12), in the synthesis of [6- / C]porphobilinogen the pyrrole 22 was acetylated with... 

---