Nitroso compounds, table

Nitrosamines, 1074, 1076 Nitrosobenzene, 629, 630 Nitroso compounds, table of, 1085 p-Nitroso derivatives, 660 N-Nitrosodiethylamine, 426 N-Nitrosodimethylamine, 426 p-Nitrosodimetlivlaniline, 562,573 N-Nitrosoethylaniline, 570 N-Nitrosomethylaniline, 562. 563, 570 p-Nitroso-N-methylanOine, 563, 574 Nitrosomethylurea. 968, 969 a-Nitroso-(3-naphthol, 958 (3-Nitrostyrene, 709, 717 a(3-Nonenoic acid, 405, 468 -Nonoic acid. 487... 

OXIMES AND NITROSO COMPOUNDS TABLE 96. NITROSO COMPOUNDS... 

The yields of the dimeric nitroso compounds are good. Thus the aliphatic nitroso compounds which previously were difficult to obtain become readily available. A series of dimeric nitroso compounds with primary and secondary alkyl groups are given in Table III. 

Tilden and Leech have prepared nitrosocyanides of limonene by the action of potassium cyanide on the nitroso compounds. The table on opposite page gives tbe melting-points and optical rotation of the principal of these and other limonene compounds. 

Common inhibitors include stable radicals (Section 5.3.1), oxygen (5.3.2), certain monomers (5.3.3), phenols (5.3.4), quinones (5.3.5), phenothiazine (5.3.6), nitro and nitroso-compounds (5.3.7) and certain transition metal salts (5.3.8). Some inhibition constants (kjkp) are provided in Table 5.6. Absolute rate constants (kj) for the reactions of these species with simple carbon-centered radicals arc summarized in Tabic 5.7. 

The data in Table 3-1 demonstrate, however, that the sequence of catalytic efficiency mentioned above is caused not by higher nitrosation reactivity k2 of the respective nitroso compounds XNO, but by the more favorable position of the equilibrium in Scheme 3-26, i.e., by higher values for A"Xno-... 

The intramolecular /zetero-Diels-Alder reactions of 4-O-protected acyl-nitroso compounds 81, generated in situ from hydroxamic acids 80 by periodate oxidation, were investigated under various conditions in order to obtain the best endo/exo ratio of adducts 82 and 83 [65h] (Table 4.15). The endo adducts are key intermediates for the synthesis of optically active swainsonine [66a] and pumiliotoxin [66b]. The use of CDs in aqueous medium improves the reaction yield and selectivity with respect to organic solvents. 

In 1976, Ross al. first reported that the powerful carcinogens, N-nitrosodimethylamine (NOMA) and N-nitrosodi-n-propyl-amine (NDPA) were found at parts per million (ppm) concentrations in certain commercial herbicide formulations (1., ). Since then, scientists have learned that carcinogenic N-nitroso compounds can be formed in a wide variety of media of interest to those who manufacture, use, or study pesticide products. Some of these nitrosation-supporting media are listed in Table I. 

Almost any class of reduced nitrogen compound can serve as the nitrosatable precursor of an N-nitroso compound. To make matters worse, every nitrogen coordination state from primary to quaternary has been converted to a nitrosamine. A glance at the list of some of the known nitrosatable substrates given in Table II illustrates what a wide variety of N-nitroso compounds analysts might expect to encounter in our complex environment. 

An attempt to estimate human daily impact of N nitroso compounds is shown in Table I. The apparent intake from food of preformed nitrosamines is comparatively low, at least in these surveys of a Western diet in England (3). The Intake directly to the respiratory tract from smoking could be somewhat larger. However, if the blood levels reported are confirmed as correct, then inputs of up to 700 meg per day of at least N nitrosodimethylamine (NDMA) may be calculated, based on pharmacokinetic considerations of data obtained in animals and extrapolated to man. It should be emphasized that no information is available at present on nitrosamide intake or in vivo formation, largely because of analytical limitations. 

This far into a nitrosamine symposium it should hardly be necessary to point out that nitrosamines are technically just one of a group of Ji-nitroso compounds that also includes nitros-amides, nitrosocarbamates, nitrosoureas, etc. Or that nitrosa-table pesticides encompass all the categories just mentioned and more. Or that many diverse pesticides, including herbicides, insecticides, and fungicides have been converted to Ji-nitroso derivatives in the laboratory (a recent review contained a 3-page, probably incomplete, compilation), or that some of the Ji-nitroso compounds thus synthesized were determined to be carcinogenic in test animals or mutagenic in various assays. 

Selected electron spin resonance data for spin adducts of C-nitroso-compounds (see also Table l)0 ... 

Rate constants for spin trapping of alkyl radicals measured by the procedures outlined here, are collected with other spin-trapping rate data in Table 5. It will be seen that most nitrone and nitroso traps scavenge reactive radicals of diverse types with rate constants generally in the range 10s-10 1 mol-1 s l. Of the nitroso-compounds, the nitroso-aromatics (except for the very crowded TBN) are particularly reactive, whilst MBN and DMPO are the most reactive nitrones. Much of the data for spin trapping by nitrones has been accumulated by Janzen and his colleagues, who have discussed in a short review how steric and electronic factors influence these reactions (Janzen et ai, 1978). 

TABLE 5. Bond lengths and angles in some nitroso compounds... 

Photoelectron spectra of amines, nitroso and nitro compounds TABLE 5. (continued)... 

In Table 13 the ionization potentials of some more C-nitroso compounds are collected. The spectrum of monomeric t-nitrosobutane126 exhibits a well separated band at 9.05 eV. The following ionizations show maxima at 11.85 and 12.46 eV. The spectrum is dominated by a strong composite band from 12.9-14.5 eV. The spectrum can be assigned by comparison with nitrosomethane. The substitution of Me by t-Bu lowers the n ionization energy of the nitroso group by 0.7 eV, whereas the n+ and it ionization energies are lowered by 1.8 and 1.7 eV, respectively. 

The PE spectrum of nitrosobenzene has been investigated by Rabalais and Colton129 and by Green and coworkers128. Unfortunately, the published IP values are considerably at variance. From the characteristic IPs of C-nitroso compounds only IP(n ) = 8.51 eV could be assigned as the first IP. IP2 and IP3 were identified as ionizations of electrons from the benzene MOs ni and 7r3 (Table 13). 

The H-NMR spectra of amino, nitro and nitroso compounds have been reviewed16,17, and the effects of these substituents on the proton chemical shifts have been investigated16. Table 4 gives these substituent effects for mono-substituted benzenes. 

TABLE 16. 1SN chemical shifts of nitroso compounds in CDCI3 measured with respect to 4.5M NH4NO3... 

Interest in nitroso compounds as intermediates for organic synthesis has faded due mainly to their potential toxic effects. Table 6, shows that activity in this field is centered mainly on occupational and environmental pollution subjects. An ample review appeared recently on V-nitroso compounds, including chemical, biochemical and analytical aspects566. 

TABLE 6. Examples of environmental and occupational protocols for nitroso compounds of industrial significance... 

TABLE 7. A-Nitroso compounds in the diet, carcinogenicity and occurrence"... 

Reduction of nitrocompounds involves a series of one-electron additions and chemical steps and an important reaction intermediate is the nitrosocompound. The redox properties of nitro- and nitroso-compounds will be discussed first. Some values of reduction potentials for nitrocompounds are collected in Table 11.1. 

Quinone oximes and nitrosoarenols are related as tautomers, i.e. by the transfer of a proton from an oxygen at one end of the molecule to that at the other (equation 37). While both members of a given pair of so-related isomers can be discussed separately (see, e.g., our earlier reviews on nitroso compounds and phenols ) there are no calorimetric measurements on the two forms separately and so discussions have admittedly been inclusive—or very often sometimes, evasive—as to the proper description of these compounds. Indeed, while quantitative discussions of tautomer stabilities have been conducted for condensed phase and gaseous acetylacetone and ethyl acetoacetate, there are no definitive studies for any pair of quinone oximes and nitrosoarenols. In any case. Table 4 summarizes the enthalpy of formation data for these pairs of species. 

In contrast to a straightforward and predictable decomposition pattern of photolysis with >400 nm light, irradiation of nitrosamides under nitrogen or helium with a Pyrex filter (>280 nm) is complicated by the formation of oxidized products derived from substrate and solvent, as shown in Table I, such as nitrates XXXIII-XXXV and nitro compound XXXVI, at the expense of the yields of C-nitroso compounds (19,20). Subsequently, it is established that secondary photoreactions occur in which the C-nitroso dimer XIX ( max 280-300 nm) is photolysed to give nitrate XXXIII and N-hexylacetamide in a 1 3 ratio (21). The stoichiometry indicates the disproportionation of C-nitroso monomer XVIII to the redox products. The reaction is believed to occur by a primary photodissociation of XVIII to the C-radical and nitric oxide followed by addition of two nitric oxides on XVIII and rearrangement-decomposition as shown below in analogy... 

Table 1 indicates our survey of prescription and non-prescription drugs. We have investigated only a single manufacturer s product for each item. Contaminants in three presciption and two over-the-counter formulations were shown to give a positive TEA response. Subsequent chemical tests showed that for the prescription drugs, the impurities were probably N-nitroso compounds, although this has not been confirmed by mass spectrometry. Several other drugs which contained TEA positive materials were demonstrated not to contain N-nitroso compounds by a series of chemical tests used in conjunction with HPLC-TEA. 

In those instances where TEA responsive materials were present, the levels were in the low ppb range (40-81 ppb). Should any of these materials be confirmed as real N-nitroso compounds, and if these are known or suspected carcinogens, then there may be a health risk for persons taking them. However, it must be emphasized that we have no evidence at present with regard to the carcinogenic risk of any of the drug product impurities indicated in Table 1. 

Properties of miscellaneous aromatic nitroso compounds are given in Table IV. 

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