Morpholine 4-nitro

Alkylation of the 5(4)-nitro compound with methyl sulfate in nonpolar solvents affords dimetridazole (91), ° an antitrichomonal agent used in veterinary practice. Alkylation with chlorohydrin leads to metronidazole (92), a drug that has found widespread use in the treatment of vaginal trichomoniasis. Finally, alkylation by means of iv-(2-chloroethyl)morpholine affords nitrimida-zine (93),... 

The reaction of 4-(l-cyclohexenyl)morpholine and ( )-(2-nitro-l-propenyl)benzene or (E)-3-(2-nitro-1-propenyl)furan gave almost exclusively the vyrc-adducts, as did the analogous reaction of l-(l-cyclohexenyl)piperidine13 14. 

In a similar vein, alkylation of 4-(5)-nitro-imidazole with N-(2-chloroethyl)morpholine affords a mixture of N-alkylated imidazoles (61 and 62). The compound containing the adjacent ring substituents (61) is the antitrichomonal agent nimorazole.15... 

Hydroxymethylation (formaldehyde) of nitro-imidazole 76 affords 77, which is oxidized to aldehyde 78. To prepare the other fragment for this convergent synthesis, reaction of epichlorohydrin with morpholine leads to the aminoepoxide 79, which is reacted with hydrazine to afford 80. Reaction of this substituted hydrazine with dimethyl carbonate affords oxazolinone 81 by sequential ester interchange reactions. Condensation of 81 with aldehyde 78 affords the antitricho-... 

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. 

TPA-Ru04 (4.5 mg, 0.013 mmol) is added to the nitro compound (0.13 mmol), A-methyl-morpholine-iV-oxide (22.7 mg, 0.194 mmol), AgOAc (43 mg, 0.258 mmol), K2CO, (90 mg, 0.65 mmol) and powdered 4A molecular sieves (0.1 g) in MeCN (2 ml). The mixture is stirred for 10 h at 40° C and Et20 (5 ml) is then added. Filtration through Celite and evaporation of the filtrate yields the ketone. 

The syntheses shown in Scheme 26 (71CB1573) are based on dibenzo-/3-tropolone (108) and its enamines. Condensation of 108 and benzoin in the presence of ammonia affords pyrrole 109. The morpholino enamine gives pyrazole 110 via benzoylation, hydrolytic elimination of morpholine, and cyclization, whereas diazo-group transfer onto the anilino enamine leads to triazole 111. Dione 108 and p-nitrophenylazide in one step give predominantly the p-nitro derivative of 111 (92G249). 

Cyclocondensation of 2-amino-5-nitro-3-pyridinecarboxamide with 4-hydroxybenzaldehyde in the presence of ZnCl2 in refluxing diethylene glycol dimethyl ether gave the pyridopyrimidine 351 <1994MIP2056742>. Reaction of ethyl 2-(l-ethoxyethylidene)amino-4,5,6-trisubstituted-3-pyridinecarboxylate with A -(2-aminoethyl)morpholine in the presence of HCl gave the polysubstituted pyridopyrimidin-4(3/7)-one 352 <1997W09719946>. 

Zu der in Bd.XI/1, S. 217ff. abgehandelten N-Alkylierung von Ammoniak und Aminen mit Sulfonsaure-alkylestern wird als weiteres detailliertes Beispiel die Herstellung von 2-Morpholino-l-oxo-cyclohexan3 durch Reaktion von Morpholin mit 2-(4-Nitro-benzol-sulfonyloxy)-l-oxo-cyclohexan beschrieben ... 

Die Umsetzung von 3,4-Dinitro-l-methyl-pyrrol mit eincm UberschuB an sekundaren Aminen wie Piperidin oder Morpholin ergibt 2,3-Dipiperidino(b7.w. Dimorpholino)-l-me-thyl-4-nitro-2,3-dihydro-pyrrol (85 bzw. 87%)z. 

Dimethyl-3,4-dinitrothiophene undergoes a different type of reaction with cyclic secondary amines. The product from the reaction with morpholine, obtained in nearly quantitative yield, has been identified as 2,5-dimethyl-rrans-2,3-dimorpholino-4-nitro-2,3-dihydrothiophene. Most notable in this reaction is the high stereospecificity. The reaction probably proceeds through initial reversible addition of a molecule of morpholine to the 2,3-double bond (Scheme 139) <80JCS(P2)1764). 

Bromination (Br2) of 4,5,6,7-tetrahydrobenzo[6]thiophen-4-one affords either a 2-bromo or a 5-bromo derivative, depending on whether the reaction is carried out at 0° in ether,445,446 or at—5 to 0°in 50% aqueous acetic acid.354 The 5-bromo derivative condenses with morpholine or potassium phthalimide to give 140a or 140b, respectively.445, 446 Hydrazinolysis of 140b fails to give any of the 5-amino derivative.445,446 On nitration, the 2-bromo derivative affords the 3-nitro compound or 141 (R = N02), depending on the reaction conditions.354 With sodium azide in PPA the 2-bromo and 2-bromo-3-... 

Unsaturated nitro compound and nitriles do not usually suffer nucleophilic attack by enols or enolates and both are good at conjugate addition. The addition of the morpholine enamine 57 of cyclohexanone to 58 demonstrates that the nitro group is more effective than the ester at promoting conjugate addition.7... 

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