Nitroso intermediate

Nitrated fluoro compounds are synthesized by electrophilic (NOz+), radical (NO2 ), or nucleophilic (NO2-) methods Indirect nitration routes can suppress the side reactions associated with severe reaction conditions and some nitration reagents Novel fluoronitro compounds, unobtainable by direct nitration, can also be pre pared For example, the nitration of (2-fluoro-2,2-dinitroethoxy)acetaldoxime followed by oxidation of the nitroso intermediate with hydrogen peroxide yields 2-fluoro-2,2-dinitioethyl 2,2-dinitroethyl ether [f] (equation 1)... 

Because the nucleophiles can be introduced at the orr/io-posidon of the nitro group, various heterocycles can be prepared via VNS and related reacdons. Indoles and related compounds are prepared via the VNS reacdon and subsequent cyclizadon. The VNS reaction of nitroarenes followed by cyclizadon v/ithEt- N-Me SiCl gives 1-hydroxyindoles fEq. 9.53. Cyclizadon is Mso catrilyzed on treatment v/ith bases, in which nitroso intermediates are postidated. 

Tricyclic antihistamines as a rule carry aliphatic nitrogen as a substituent on a side chain attached to the central ring the side chain nitrogen may be part of a heteroaromatic ring. Conjugate addition of p-chloroaniline (49) to the substituted vinylpyridine 50 gives the alkylated aniline 51. Treatment of that intermediate with nitrous acid leads to N-nitroso intermediate 52 which is then reduced to the hydrazine (53). Reaction of 53 with N-methyl-4-piperidone... 

Let us note that there is no need for any organic nitroso intermediate for N2 formation. Therefore, two adsorbed oxygen species Oads (ex-NO) are remaining, strongly adsorbed... 

The furazan ring can be constructed by the one-pot reaction of iV-(5,5-dimethyl-3-oxocyclohexenyl)-.S,.S-diphenyl-sulfilimine 272 with isopentyl nitrite <2006SC2087> and also by a one-pot procedure from sulfinimines 273, without isolation of the nitroso intermediates, in refluxing toluene (Scheme 71) <2002T10073>. 

All reactions initially produce silyl nitronates, which react with nucleophiles to give nitroso intermediates A. The latter give products 114 to 116 either during the reaction or upon aqueous treatment. 

These procedures differ in the nature of the initiating nucleophile (Nu, ) and the reaction temperature range. For anions derived from secondary AN a lower concentration of active nitroso intermediate B is strongly recommended. Therefore, the C,C-coupling of anions obtained from secondary AN is realized at higher temperature (see Table 3.32). 

This suggests that the attack of the thiolate anion, at least with this product, occurs principally on the 3-position of the furoxan ring. An alternative mechanism to that discussed above was proposed to explain NO-donation by this product. It implies the preliminary cleavage of the 1-2 bond of the furoxan ring, rather than of the 2-3 bond as suggested by Feelisch, to give a tertiary nitroso intermediate. Reasonable mechanisms may be put forward to explain the production of different NO-redox forms from this intermediate [20] (Scheme 6.9). Interestingly, some furoxans, such as 31 and related compounds, produce NO, detected as nitrite, spontaneously without the assistance of thiols [21]. 

Sterically hindered amino substituents or amino substituents with electron-with-drawing groups in the 3-position of the sydnonimine ring, as in Marsidomine 88, C89-4095 89 or C4144 90, have little impact on the stability of the heterocyclic system toward ring opening, but are able to slow down the process of oxidative NO-release from the nitroso intermediates [107]. 

Due to the electron-demanding carbamoyl substructure on the nitroso hydrazine intermediates 129 the oxidative process that initiates the NO-release is much slower than with the active sydnonimine metabolites. The elimination of HNO from the nitroso intermediates and the subsequent oxidation to NO cannot be completely ruled out for this type of compounds. In vivo, an alternative, possibly thiol mediated route for the NO formation plays a role in the activity [147]. In this reaction the formation of nitrosothiols as unstable NO precursor intermediates is the most likely process. 

Nitric oxide formation from hydroxyurea requires a three-electron oxidation (Scheme 7.15) [114]. Treatment of hydroxyurea with a variety of chemical oxidants produces NO or NO-related species , including nitroxyl (HNO), and these reactions have recently been extensively reviewed [114]. Many of these reactions proceed either through the nitroxide radical (25) or a C-nitroso intermediate (26, Scheme 7.15) [114]. The remainder of the hydroxyurea molecule may decompose into formamide or carbon dioxide and ammonia, depending on the conditions and type of oxidant (one-electron vs. two electron) employed. 

The reduction of aliphatic nitrocompounds in acid solution proceeds in two steps. First the nitrosocompound is formed. A low steady state concen ation of 2-methyl-2-nitrosopropane has been detected during the reduction of 2-methyl-2-nitropropane [13]. At the cathode potential necessary to attach the first electron to a nitro group, the nitroso intermediate undergoes further reduction to the hydroxyla-mine. When the nitrocompound has one a-hydrogen substituent, tautomerism of the nitroso intermediate to an oxime is in competition with further reduction. Both temperature and proton availability affect the rate of this isomerisation. Reduction of aliphatic nitrocompounds to the hydroxylamine is usually carried out in acid solution at 0-5° C to minimise oxime formation [14, 15], The hydroxylamine is stable towards further reduction in acid solution. Oximes in acid solution are reduced... 

Most reactions of nitroso intermediates are however too slow to compete with further reduction. In these cases it is necessary to carry out the tandem reduction to the hydroxylamine stage and then oxidation back to the nitroso compounds using the type of double-cell sketched in Fig. 11.2. The intermediate is then allowed to... 

Biochemical transformations of the —C=N—OH function of synthetic drugs to an NO and to nitroso intermediates " were recently demonstrated as a new pathway for metabolic activation of oxime-containing molecules. These reactions were recently explored in detail, and may underlie possible biochemical transformations of the —C=N— OH moiety in mammalian tissues, which are likely to be catalyzed by cytochrome P450 and by flavin-containing monooxygenase " . 

Metabolic activation of a,/ -unsaturated oximes, such as 46, leads to the conclusion that this class of unsaturated oximes are pro-haptens. They can undergo epoxidation that eventually produces reactive nitroso intermediates which act as strong contact sensitizers . Here, the oxime function plays a major role in the chemical activation that results in the reactive nitrosoaUcenes. It was further pointed by the authors that oximes can be hydrolyzed in vivo to the corresponding carbonyl compounds which are potential allergens. 

Finally, an interesting deamination reaction of aziridines was reported, in which treatment of N-unsubstimted aziridines (152) with dinitrogen tetroxide (2 equiv) in the presence of Et3N results in clean deamination to provide the corresponding alkenes (154) with remarkably high yields (>90%). The reaction is believed to proceed via the N-nitroso intermediate 153, so that the driving force for the reaction is liberation of N O <99SC1241>. 

The diimines (229) differ considerably in thermal stability. The sulfonyl compounds (226) and (229a) are stable crystalline compounds which rearrange at elevated temperatures. The acyl derivatives (229b and c) and the dianion formed by demesylation of (226) undergo retrocyclization below -15 °C at a rate equal to or faster than loss of N2O from N- nitroso intermediates. 

J.C. Hoffsomer, D.J. Glover, Thermal Decomposition of 1,3,5-Trinitro-l,3,5-Triazine (RDX) Kinetics of Nitroso Intermediates Formation, Combust. Flame, 59 (1985) 303. 

Summary MON is prepared by nitrating maltose with 99% nitric acid in the presence of urea, followed by the presence of fuming sulfuric acid. The urea is added to form a urea nitroso intermediate, which aids in the nitration of the maltose. After the reaction, the mixture is refluxed for a short period, and then drowned into ice water to precipitate the product. Recrystallization yields a purity of 99%. 

Summary 2,4-Dinitrophenol is prepared by reacting phenol with sodium hydroxide, sodium nitrite, and dilute nitric acid. A nitroso intermediate is formed, which is then converted to 2,4-dinitrophenol by treatment with 60% nitric acid. The 2,4-Dinitrophenol is then recovered by filtration. After which, the DNP is washed and dried. Commercial Industrial note For related, or similar information, see Application No. 365,208, May 30, 1973, by David Anthony Salter, 35, Roseacres, Takely, Essex, England, Robert John James Simkins, 3, Upper Park, Harlow, Essex, England. Part or parts of this laboratory process may be protected by international, and/or commercial/industrial processes. Before using this process to legally manufacture the mentioned explosive, with intent to sell, consult any protected commercial or industrial processes related to, similar to, or additional to, the process discussed in this procedure. This process may be used to legally prepare the mentioned explosive for laboratory, educational, or research purposes. 

N-oxidation can occur in a number of ways to give either hydroxylamines from primary and secondary amines [Eqs. (11) and (12)], hydroxamic acids from amides, or N-oxides from tertiary amines [Eq. (13)]. The enzyme systems involved are either cytochrome P450 or a flavoprotein oxygenase. Hydroxylamines may be further oxidized to a nitro compound via a nitroso intermediate [Eq. (11)]. Oximes can be formed by rearrangement of the nitroso intermediate or N-hydroxylation of an imine, that could in turn be derived by dehydration of a hydroxylamine [Eq. (11)]. N-Oxides may be formed from both tertiary arylamines and alkylamines and from nitrogen in heterocyclic aromatic systems, such as a pyridine ring. 

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