Nitrosation application

Hexamethyleneimine, N-nitroso-synthesis, 7, 518 Hexamethylenetetramine applications, 3, 529 degradative nitrosation, 3, 488 food preservative, 1, 411 quatemization, 3, 488 reactivity, 3, 487 88 structure, 2, 6 synthesis, 3, 509... 

The formation of nitrosamines in aprotic solvents has applicability to many practical lipophilic systems including foods (particularly bacon), cigarette smoke, cosmetics, and some drugs. The very rapid kinetics of nitrosation reactions in lipid solution indicates that the lipid phase of emulsions or analogous multiphase systems can act as "catalyst" to facilitate nitrosation reactions that may be far slower in purely aqueous media (41, 53, 54). This is apparently true in some cosmetic emulsion systems and may have important applicability to nitrosation reactions in vivo, particularly in the GI tract. In these multiphase systems, the pH of the aqueous phase may be poor for nitrosation in aqueous media (e.g., neutral or alkaline pH) because of the very small concentration of HONO or that can exist at these pH ranges. 

Safe" secondary amines resulting in non-carcinogenic N-nitroso compounds after nitrosation (German Patent Application No P 3029 318 6)... 

S -nitrosothiols, several of which occur naturally, e.g., iS -nitrosocysteine and S-nitrosoglutathione, have an important role in NO transport and regulation in biological systems. Potential applications of RSNO compounds include their use as vasodilators in the treatment of angina and in the search for a cure for male impotence.11 The most convenient route to S-nitrosothiol formation is the nitrosation of thiols. 

The syntheses of N-hydroxy-N-nitrosamines are usually carried out by the nitrosation of the corresponding N-hydroxyamines (Scheme 3.8) [123, 124]. N-Hydroxyamines are readily obtained by the reduction of the corresponding nitro-compounds. The most efficient methods are neutral or basic reactions. Recent applications of this method have resulted in the preparation of a variety of cupferron derivatives (Scheme 3.8) via nitrosation of phenylhydroxylamine with amyl nitrite/ammonia [125] or methyl nitrite/ammonia [126]. Behrend and Konig have shown that the organic... 

The constants Ka increase with increasing nucleophilicity of X (Cl < Br < scisr < (H2N)2CS). The rate constants for the nitrosation step (ki in equation 26) are close to diffusion control in the case of X = Cl or Br but lower for reactions with nitrosation reagents XNO with stronger nucleophiles X (as expected). As in the case of diazotization by N203 (Section II.E), either the formation of XNO or the nitrosation may be rate-limiting. The rate equation 28 is applicable only for reactions with a steady-state of XNO. 

Five methods for the nitrosation of amides will be mentioned here. Of these, the methods using dinitrogen tetroxide appears to have the widest applicability in terms of the classes of amides which can be nitrosated and the purity of the products obtained. However, the other methods also have special utility. 

In view of the general applicability of dinitrogen tetroxide as a nitrosating agent for amides, the application of this reagent for reaction with other nitrogen compounds is strongly indicated. 

There appears to have been no systematic study, at least in recent years, of the nitrosation of substituted hydrazines. Work at the beginning of the century indicates that the nitrosation of primary hydrazines may result in the intermediate formation of nitroso compounds, but that these compounds subsequently react further, in the presence of nitrous acid, to give a variety of products. 1-Benzyl-1-nitrosohydrazine evidently has been prepared and subsequently benzoylated. The resultant A-nitrosohydrazide apparently is reasonably stable [61]. More recently, A-nitroso-A-alkylhydrazides have been prepared by ring cleavage of compounds such as A-benzamidopiperidine and A-benzamidopyrrolidine [62]. This method, however, does not appear to have very general applicability. 

In addition to the nitration of phenols by substitution of sulpho groups (p. 130) the method of nitrosation of phenols, followed by oxidation of the nitroso to the nitro group has some practical application ... 

Of the methods for determining lignin in solution based on a specific chemical reaction, that involving nitrosation, the so-called Pearl-Benson method, has found the widest application. In this procedure, reaction of the phenolic units in lignin with acidified sodium nitrite leads to the formation of a nitrosophenol which, upon addition of alkali, is tautomerized to an intensely colored quinone mono-oxime. The absorbance of the latter structure is measured at 430 nm and related to lignin concentration by calibration with a standard lignin. The procedure described below is essentially that developed by Barnes et al. (1963), who modified the original Pearl-Benson method (Pearl and Benson 1940) to improve its sensitivity. 

Summary 4,6-Dinitroresorcinol is prepared by the action of 70% nitric acid on resorcinol diacetate. Some urea is added in-order to control the nitration and ensure no by-product nitrosation takes place. After the addition of the 70% nitric acid, the intermediate produced is treated with 90% nitric acid yielding the 4,6-dinitroresorcinol as a golden yellow solid. Commercial Industrial note For related, or similar information, see Application No. 001,243, January 7,1987, by SRI International, to Robert J. Schmitt, (Mountain View, CA, David S. Ross, Palo Alto, CA, James F. Wolfe, Palo Alto, CA. 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. 

The purging of nitrogen oxides from exhaust gases (913) and treatment of smoking materials (914) with ascorbates are of interest, particularly the latter, wherein a lower production of potentially carcinogenic nitrosated compounds may result if the application were to be put into effect. 

NDMA has been found in soil at 1-8 ig/kg (dry basis) in Belle and Charleston, WV, New Jersey and New York City (Fine et al. 1977c). It is speculated that occurrence of NDMA in soil may have arisen from (a) absorption of NDMA in air, (b) absorption of dimethylamine from air and its subsequent N-nitrosation, or (c) from pesticide application. 

The vast literature on applications of PTC in substitution reactions is mainly restricted to nucleophilic substitution reactions with an anionic reagent. However, recently the use of PTC in electrophilic reactions, like diazotization andazocou-pling C-and N-nitrosation, C-alkylation, acid hydrolysis of esters, chloromethylation, nitrite-initiated nitrations, and so on have been reported(Velichko et al., 1992 Kachurin et al., 1995). Alkylbenzene sulfonates and lipophilic sodium tetrakis[3,5-bis(trifluoromethyl)phenylboranate are typical electrophilic PT catalysts. Lipophilic dipolar molecules of the betaine type and zwitterionic compounds also function well as PT agents for both nucleophilic as well as electrophilic reactions. 

Summarizing the work accomplished on the synthesis of aliphatic diazo compounds by nitrosation of aminoalkanes, it has to be emphasized that precaution is absolutely necessary in its application. With few exceptions (e.g., amino-a,a -di-carbonyl compounds), the results are unreliable for most classes of amines. This method is not recommended if the specific compound has not been described so far in the literature, or if another method (see Sects. 2.4-2.6) is available. 

A mechanistically different type of nitrosation was discovered by Keefer and Roller (1973), namely a nitrosation of secondary aliphatic amines with nitrite anions in alkaline solution, catalyzed by aldehydes. Although it is unlikely to be applicable to diazotization, i. e., to primary amines, it will be mentioned here because it is a good example of the fact that, in chemistry, particularly in organic chemistry, for a certain type of reaction, e. g., nitroso-de-protonation (which includes substitution of protons bonded to C, N, O, S, etc., atoms), practically all methods follow the same basic pattern (in the case of nitrosation substitution by an electrophilic nitrosating reagent). The Keefer-Roller nitrosation is apparently different if one looks at the stoichiometric equation (4-8). A careful kinetic investigation (Casado et al., 1981b, 1984 a) on the concentration and pH dependence of this reaction revealed that the nitrite anion and free amine base enter the substitution process and that formaldehyde is a true catalyst, as it is not required in equimolar amounts. 

As an outsider in the chemistry of bicyclic aliphatic hydrocarbons, I have the feeling that these reactions are intrinsically so complex that it is too difficult to deduce from them generally applicable rules for deamination mechanisms. It would appear that concentration on reagents as simple in structure as possible would be more promising, as purity determinations by instrumental analyses of all types are easier to interpret and as the number of products would be smaller. This is clearly indicated by some of the reactions discussed in Section 7.3, particularly Brosch and Kirmse s stereochemical investigation (1991) of the [l- H]butylamine deamination and the reactions investigated by Fishbein s group, namely the first steps of the methylamine nitrosation (Hovinen and Fishbein, 1992 Hovinen et al., 1992), the decomposition... 

There is a paucity of information regarding the environmental formation or stability of N-nitrosopesticides. For example, the extensive use of atrazine in crop production programs utilizing heavy application of nitrogen fertilizers has raised the possibility of its N-nitrosation in soils (65). 

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