Morpholine

About: Morpholine is a research topic. Over the lifetime, 5411 publications have been published within this topic receiving 51063 citations. The topic is also known as: diethylene imidoxide & diethylene oximide.

Photogeneration and reactivity of naphthoquinone methides as purine selective DNA alkylating agents.

Abstract: A one-step protecting-group-free synthesis of both 6-hydroxy-naphthalene-2-carbaldehyde and the bifunctional binaphthalenyl derivative afforded 6-hydroxymethylnaphthalen-2-ol, 6-methylaminomethyl-naphthalen-2-ol, [(2-hydroxy-3-naphthyl)methyl]trimethyl ammonium iodide, and a small library of bifunctional binol analogues in good yields. Irradiation of naphthol quaternary ammonium salt and binol-derivatives (X = OH, NHR, NMe3+, OCOCH3, and l-proline) at 310 and 360 nm resulted in the photogeneration of the 2,6-naphthoquinone-6-methide (NQM) and binol quinone methide analogues (BQMs) by a water-mediated excited-state proton transfer (ESPT). The hydration, the mono- and bis-alkylation reactions of morpholine and 2-ethanethiol, as N and S prototype nucleophiles, by the transient NQM (λmax 310, 330 nm) and BQMs (λmax 360 nm) were investigated in water by product distribution analysis and laser flash photolysis (LFP). Both the photogeneration and the reactivity of NQM and BQMs exhibited striking differences. BQM...

Nickel‐Catalyzed Formation of a Carbon–Nitrogen Bond at the β Position of Saturated Ketones

Abstract: Gone fishing: When propiophenone and related ethyl ketones are treated with morpholine in the presence of K(3)PO(4), chlorobenzene, and [Ni(cod)(2)]/PMe(3) catalyst, a carbon-nitrogen bond is formed selectively at the beta position (see scheme; cod = cycloocta-1,5-diene). Secondary amines were employed as substrates to give the corresponding beta-enaminones.

Morpholine derivatives greatly enhance the selectivity of mammalian target of rapamycin (mTOR) inhibitors.

Abstract: Dramatic improvements in mTOR-targeting selectivity were achieved by replacing morpholine in pyrazolopyrimidine inhibitors with bridged morpholines. Analogues with subnanomolar mTOR IC(50) values and up to 26000-fold selectivity versus PI3Kalpha were prepared. Chiral morpholines gave inhibitors whose enantiomers had different selectivity and potency profiles. Molecular modeling suggests that a single amino acid difference between PI3K and mTOR (Phe961Leu) accounts for the profound selectivity seen by creating a deeper pocket in mTOR that can accommodate bridged morpholines.

The chemistry of nitroso-compounds. Part 11. Nitrosation of amines by the two-phase interaction of amines in solution with gaseous oxides of nitrogen

Abstract: The formation of secondary N-nitrosoamines when MeCN solutions of amines are brought into contact with gaseous NO, N2O3, and N2O4 at 25 °C is reported. With NO, N-nitrosoamine formation from piperidine, morpholine, and diphenylamine occurs very slowly (t½ca. 8 days). Reaction rates are largely independent of the amine, suggesting that oxidation of NO by adventitious oxygen is the slow step. Very much faster reactions are observed, however, with N2O3 and N2O4. With a ca. 10-fold excess of N2O3 or N2O4, quantitative yields of both N-nitrosopiperidine and N-nitrosodiphenylamine are found in less than 3 min. With a 27-fold excess of piperidine and N2O4 only, ca. 8%N-nitropiperidine and 92%N-nitrosopiperidine are obtained. Rapid reactions also ensue when solutions of either primary aromatic or secondary amines dissolved in 0.1M-aqueous NaOH are brought into contact with gaseous N2O3 and N2O4. With a ca. 2–400-fold excess of these nitrogen oxides, 12–65% of the amine is converted either to N-nitrosoamine or diazonium ion in less than 3 min. Competitive hydrolysis of the nitrogen oxide by the solvent is not HO–-catalysed and the amine : H2O reactivities are in ca. 1 000 : 1. The extent of N-nitrosation varies insignificantly over a wide range of basicities (pKa, 11.12 to –1.0), but no reaction occurs with either 2,4-dinitroaniline or N-butyl-acetamide. With N2O4, smaller amounts of N-nitroamines form concurrently and increase with decreasing amine basicity. The results are discussed in relation to amine nitrosation by N2O3 and N2O4 in aqueous acidic solutions. It is suggested that the lower selectivity for the dissolved gaseous reagents may relate to the presence of more reactive N2O3 and N2O4 isomers. The results also show that carcinogenic N-nitrosoamines form under a much wider range of experimental conditions than previously known, some of which are relevant to atmospheric pollution.

Synthesis and Biological Activity of 3- and 5-Amino Derivatives of Pyridine-2-carboxaldehyde Thiosemicarbazone

Abstract: A series of 3- and 5-alkylamino derivatives, as well as other structurally modified analogues of pyridine-2-carboxaldehyde thiosemicarbazone, have been synthesized and evaluated as inhibitors of CDP reductase activity and for their cytotoxicity in vitro and antineoplastic activity in vivo against the L1210 leukemia. Alkylation of 3- and 5-amino-2-(1,3-dioxolan-2-yl)pyridines (1, 2) resulted in corresponding 3-methylamino, 5-methylamino, 3-allylamino, 5-ethylamino, 5-allylamino, 5-propylamino, and 5-butylamino derivatives (5, 6, and 11-15), which were then condensed with thiosemicarbazide to yield the respective thiosemicarbazones (7, 8, and 16-20). Oxidation of 3,5-dinitro-2-methylpyridine (21) with selenium dioxide, followed by treatment with ethylene glycol and p-toluenesulfonic acid, produced the cyclic ethylene acetal, 23. Oxidation of 2-(1,3-dioxolan-2-yl)-4-methyl-5-nitropyridine (26) with selenium dioxide, followed by sequential treatment with sodium borohydride, methanesulfonyl chloride, and morpholine afforded the morpholinomethyl derivative 30. Catalytic hydrogenation of 23 and 30 with Pd/C yielded the corresponding amino derivatives 24 and 31. Catalytic hydrogenation of 5-cyano-2-methylpyridine (33) with Raney nickel, followed by treatment with acetic anhydride, gave the amide derivative 35. N-Oxidation of 35, followed by rearrangement with acetic anhydride, produced the acetate derivative, 5-[(acetylamino)methyl]-2-(acetoxymethyl)pyridine (37). Repetition of the N-oxidation and rearrangement procedures with compound 37 yielded the diacetate derivative 39. Condensation of compounds 24, 31, and 39 with thiosemicarbazide afforded the respective 3,5-diaminopyridine-, 4-(4-morpholinylmethyl)-5-aminopyridine-, and 5-(aminomethyl)pyridine-2-carboxaldehyde thiosemicarbazones (25, 32, and 40). The most biologically active compounds synthesized were the 5-(methylamino)-, 5-(ethylamino)-, and 5-(allylamino)pyridine-2-carboxaldehyde thiosemicarbazones (8, 17, and 18), which were potent inhibitors of ribonucleotide reductase activity with corresponding IC50 values of 1.3, 1.0, and 1.4 microM and which produced significant prolongation of the survival time of L1210 leukemia-bearing mice, with corresponding optimum % T/C values of 223, 204, and 215 being obtained when administered twice daily for six consecutive days at dosages of 60, 80, and 80 mg/kg, respectively.