- Kinetic Study of the Nitrosation Reaction of 1,3-Dimethylurea in Dioxane-Water Mixtures
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The nitrosation of dimethylurea has been studied in dioxane-water mixtures showing that the kinetic characteristics of the reaction depend on the proportion of dioxane in the medium.Adding dioxane to pure water causes the reaction rate to decrease, and pass through a minimum as a certain concentration of dioxane is reached.The further addition of dioxane increases the reaction rate steadily.At low concentrations of dioxane the system shows the behaviour seen in water, i.e. catalysis by bases and not by nucleophiles, suggesting proton transfer as the slow step.At very high proportions of dioxane, halides and thiocyanate catalyse the process, which is interpreted in terms of the formation of the corresponding nitrosyl halides which may act as efficient nitrosating agents towards the urea.The observed order of efficiency of the catalysts is the opposite to that seen in nitrosation or diazotization processes in water.
- Bravo, Carlos,Herves, Pablo,Iglesias, Emilia,Leis, J. Ramon,Pena, M. Elena
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- Kinetic study of the nitrosation of 1,3-dialkylureas in aqueous-perchloric acid medium
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The kinetics of the nitrosation of 1,3-dimethyl (DMU), 1,3-diethyl (DEU), 1,3-dipropylurea (DPU), 1,3-dibuthyl (DBU), and 1,3-diallylurea (DAU) were studied in a conventional UV/vis spectrophotometer in aqueous-perchloric acid media. The kinetic study was carried out using the initial rate method. The reaction rate observed was r = k[H+]2/[H+] + Ka [Diurea][Nitrite] where Ka is the acidity constant of nitrous acid. The diureas exhibited the reactivity order DMU ? DEU > DPU > DAU, which can be interpreted as a function of the steric impediment generated by the R alkyl group in the rate controlling step. A probable relationship between both the chemical reactivity and structure of the nitrosable substrate with the biological activity of the N-nitroso compounds generated is proposed.
- Gonzalez-Alatorre, Guillermo,Guzman-Maldonado, Salvador H.,Escamilla-Silva, Eleazar M.,Loarca-Pina, Guadalupe,Hernandez Benitez, Carlos
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- Alternative synthetic routes to N-methyl-1,2,4-triazoline-3,5-dione (MeTAD) and other triazolinedione derivatives
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N-Methyl-1,2,4-triazoline-3,5-dione (MeTAD) is a powerful electrophile and a versatile synthetic reagent. In this Letter we describe two methods for the synthesis of N-methylurazole, the direct precursor to MeTAD, on gram scales and in good yields. Both methods provide pure urazole while avoiding the necessity of large scale purification via column chromatography or recrystallization. One of the methods proved to be amenable for the synthesis of derivatives other than N-methyl.
- Breton, Gary W.,Turlington, Mark
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supporting information
p. 4661 - 4663
(2015/02/19)
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- HETEROCYCLIC HYDRAZONE COMPOUNDS AND THEIR USES TO TREAT CANCER AND INFLAMMATION
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The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).
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Page/Page column 65
(2011/02/24)
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- Application of N-nitrosoureas in the synthesis of organophosphorus compounds
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N-nitrosoureas which are readily accessible from the reaction of urea derivatives with sodium nitrite and aqueous H2SO4 reacted with acetylenic esters in the presence of Ph3P in ethyl acetate at ambient pressure to give stable phosphorus ylides. This methodology is introduced as a simple and inexpensive procedure for the preparation of organophosphorus compounds in excellent yields.
- Afshar, Davood Aghaei,Islami, Mohammad Reza
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scheme or table
p. 509 - 511
(2009/04/06)
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- Solvent-induced changes in nitrosation mechnisms. Part 3. The effects of tetrahydrofuran-water and dimethyl sulfoxide-water mixtures on the nitrosation of ureas
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Kinetic studies of the nitrosation of 1,3-dimethylurea and 2-imidazolidone in tetrahydrofuran-water and dimethyl sulfoxide-water mixtures have been carried out.In tetrahydrofuran-water mixtures, the results obtained show that the kinetic characteristics of the reaction depend on the proportion of tetrahydrofuran in the medium.At low concentrations of organic solvent, the reaction is not catalysed by chloride ions and the reaction mechanism is probably the same as in pure water.At very high proportions of tetrahydrofuran (more than 80percent by weight), there is a change in the reaction mechanism.Halide ions catalyse the process, which is interpreted in terms of formation of the corresponding nitrosyl halides which act as efficient nitrosating agents of ureas.In dimethyl sulfoxide-water mixtures the results obtained show that the addition of the organic solvent up to 85percent by weight of dimethyl sulfoxide inhibits the reaction rate, which increases slightly upon further increasing the proportion of dimethyl sulfoxide.However, unlike other organic solvents in dimethyl sulfoxide-water mixtures we did not observe catalysis by halide ions.The reaction mechanism seems to be the same as in pure water, with the proton transfer from the protonated nitroso compound to the medium being the rate limiting step.
- Herves, P.,Leis, J. R.
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p. 2035 - 2040
(2007/10/03)
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- Solvent-induced Mechanistic Changes in Nitrosation Reactions. Part 2. Effect of Acetonitrile-Water Mixtures in the Nitrosation of Ureas
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The nitrosation of 1,3-dimethylurea in acetonitrile-water mixtures has been studied kinetically.The results obtained show that the addition of acetonitrile until the medium holds 70percent acetinitrile by weight inhibits the reaction.The reaction is not catalysed by chloride ions in these circumstances, and the reaction mechanism is probably the same as in pure water.Addition of acetonitrile to a solution already containing more than 70percent acetonitrile increases the reaction rate, and catalysis by halides becomes possible.The change in reaction mechanism this suggests was studied in detail in a medium containing 90percent acetonitrile.The reaction rate increases non-linearly with increasing halide concentration and acidity, but seems to tend to the same limiting value in all cases, depending only on the nitrous acid and urea concentrations.Nitrosyl halides are therefore good nitrosating agents of ureas, though the catalytic efficiency of the different halides is the reverse of that in water, probably because of solvation-induced changes in their nucleophilicity.The tendency of the reaction rate towards a limiting value is evidence that the mechanism changes with the catalyst or acid concentration.In the limit, the reaction rate will only depend on nitrous acid and urea concentrations; this is consistent with a limiting step consisting of the rearrangement of the "nitrosourea", the nitroso group transferring from the more nucleophilic O atom to the N atom.Thus, there is direct kinetic evidence that the nitrosation of amides occurs initially on oxygen.
- Bravo, Carlos,Herves, Pablo,Leis, J. Ramon,Pena, M. Elena
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p. 2091 - 2096
(2007/10/02)
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- Kinetics and Mechanism of the Formation and Decomposition of N-Nitrosoamides and Related Compounds
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Kinetic studies of the nitrosation reactions of ethyl N-ethylcarbamate, N,N'-dimethylurea, and 2-imidazolidone have shown that all are subject to primary solvent isotope effects and to general base catalysis with bases of pKa in the range 0.6-4.6.Both these features are indicative of a slow proton transfer.The characteristics of this proton transfer and the reactivity of the substrate depend to a large extent on the nature of the substrate: for ethyl N-ethylcarbamate the Broensted plot is linear (β=0.34) and the solvent isotope effect is 5.5; for N,N'-dimethylurea*-he curved Broensted plot suggests that the reaction with acetate ion is diffusion-controlled, and the isotope effect is 3.2 in the absence of added base and 1.1 when the reaction is catalysed by acetate; for 2-imidazolidone the slightly curved graph of reaction rate against base concentration shows the proton donor to be an intermediate in the steady state, and the solvent isotope effects for the uncatalysed and acetate-catalysed reactions are 2.9 and 1.4, respectively.These facts suggest that the protonated intermediate has a near-zero pKa value.Complementary studies of the denitrosation of N-nitroso-N-methylurea, N-nitroso-N,N'dimethylurea, and N-nitroso-2-imidazolinone have shown that the rate-controlling step of each of these reactions is protonation of the substrate.These data, together with those from the nitrosation experiments, imply a pKa of ca. -12 for the nitroso-amide.The discrepancy between the two results suggests that nitrosation initially takes place at the oxygen atom; this followed first by a slow proton transfer and subsequently by a fast internal rearrangement to produce the thermodinamically more stable N-nitroso-amide.
- Castro, Albino,Iglesias, Emilia,Leis, J. Ramon,Pena, M. Elena,Tato, Jose Vazquez
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p. 1725 - 1730
(2007/10/02)
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- Synthesis of Novel N-Nitrosothioureas and Examination of Their Mechanisms of Formation by High-Field Nitrogen-15 and Carbon-13 Nuclear Magnetic Resonance Spectra of Specifically Labeled Compounds
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An examination by 15N NMR of Na15NO2 under various conditions of acidity led to the identification of several electrophilic nitrogen species.This permitted the selection of reaction conditions of low acidity which favor nitrosation at the nitrogen atom of thioureas rather than on the normally more reactive sulfur, leading to the isolation of novel N-nitrosothioureas.In contrast it was shown by employing 15N and 13C labeling that higher acidity conditions favor reaction via a detectable thionitrosyl intermediate.
- Lown, J. William,Chauhan, Shive M. S.
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p. 507 - 512
(2007/10/02)
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- Synthesis of Nitrosothioureas. 15N N.M.R. Evidence for the Formation of Thionitrosyl Compounds in the Nitrosation of Thioureas
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Nitrosothioureas may be prepared by treatment of thioureas with NaNO2 in 0.1 N HCl at -5 deg C by direct N-nitrosation whereas 15N n.m.r. studies at -10 deg C which employed specifically 15N-enriched compounds revealed the intermediacy of a thionitrosyl compound under more acidic conditions which gave the urea by hydrolysis.
- Lown, J. William,Chauhan, Shive M. S.
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p. 675 - 676
(2007/10/02)
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- Conformational Preferences in Alkylnitrosoureas
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The spectroscopic properties of several N-alkyl-N-nitrosoureas, N,N'-dialkyl-N-nitrosoureas, and N,N',N'-trialkyl-N-nitrosoureas have been studied in carbon disulfide and chloroform solutions.The NH stretching frequencies in the IR spectra have been observed in both concentrated and dilute solution and in the presence of added dioxane.The results indicate that there is a strong intramolecular hydrogen bond in the mono- and dialkylnitrosoureas.The chemical shifts and line widths of the NMR spectra have also been studied in these solvents.The large chemical shift differences, about 1.3 ppm, for the NH protons in the monoalkylnitrosoureas and other spectroscopic features in the monoalkyl- and dialkylnitrosoureas also indicate that an intramolecular hydrogen bond contributes to a strong conformational preference.The temperature dependence of the NMR spectra of several N,N',N'-trialkyl-N-nitrosoureas establishes that the energy barrier for rotation about the carbon dialkylamide bond is about 13 kcal mol-1.Dipolar resonance interactions are primarily responsible for this barrier.This interaction is augmented by a strong, 8-10 kcal mol-1, hydrogen bond in the mono- and dialkylnitrosoureas.
- Snyder, John K.,Stock, Leon M.
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p. 886 - 891
(2007/10/02)
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