Nitroso, amides

Other compounds with nitrogen-nitrogen bonds have been used instead of diazonium salts. Among these are N-nitroso amides [ArN(NO)COR], triazenes, and azo compounds. Still another method involves treatment of an aromatic primary amine directly with an alkyl nitrite in an aromatic substrate as solvent. ... 

The aryl radical thus formed attacks the substrate to give the intermediate 1 (p. 898), from which the radical 26 abstracts hydrogen to give the product. N-Nitroso amides probably rearrange to N-acyloxy compounds, which cleave to give aryl radicals ... 

A method for the preparation of olefins from primary amines is shown in equation 120. Treatment of 2-(4-bromophenyl)ethylamine (358) with acetic acid, acetic anhydride and sodium nitrite generates the nitroso amide 359, which decomposes to 4-bromostyrene in the presence of rhodium(II) acetate. The procedure is thus a mild, non-basic alternative to the classical Hofmann elimination of amines396,397. 

For a report of formation of about 15% ortho product in the case of N,N-diaryl-N-nitroso amides, sec Titova Arinich Gorelik /. Org. Chem. USSR 1986, 22, 1407. 

The N-N bond of A-nitroso amides is also easily cleaved by hydrochloric acid.161... 

Analoge Verfahren existieren fur sek. Amide. Hierzu sind u. a. die Nitrosierung mit Nitro-sylchlorid413 oder Natriumnitrit414 in Acetanhydrid oder Tetrachlormethan zu zahlen. Die primar gebildeten N-Nitroso-amide zerfallen thermisch in die entsprechenden Carbonsauren. 

Bei der Umsetzung von Alkyl(Aryl)amiden mit Natriumnitrit bzw. Distickstofftetroxid entstehen uber die Zwischenstufe der N-Nitroso-amide unter Stickstoff-Abspaltung die entsprechenden Carbonsaure-ester363. 

This problem is not encountered in the thermal rearrangement of N-nitroso amides (7.10, R = alkyl). Aliphatic N-nitroso amides were first studied by von Pechmann (1898 a). The rearrangement was originally investigated and elucidated for aromatic A-nitroso amides by Huisgen and others (see summary by Zollinger, 1994, Sect. 6.7.5). 

Huisgen s work clearly showed that, in the rearrangement of the A-nitroso amides, the (jE )-diazo ester (7.11) is formed. Ionization of (7.11) leads to an ion pair (7.12), in which the distance between the C-atom adjacent to the diazonio group and the carboxylate group is greater than in the ion pair of the same stoichiometry, but formed by addition of a carboxylic acid to a diazoalkane (7.14). For obvious reasons, the carboxylate anion formed in such a protonation of a diazoalkane in an aprotic solvent is closer to the C-atom to be protonated. We will see in Section 7.3 that this hypothesis is consistent with different product ratios of dediazoniations of diazonium-carboxylate ion pairs originating from these two routes of formation. 

Instead of A-nitroso amides (7.10, R = alkyl or aryl), A-nitroso carbamates (7.10, R = OR") and A-nitroso ureas (7.10, R = NHR) can also be used (Kirmse and Wachtershauser, 1967 Hecht and Kozarich, 1973). More recently, Kirmse s group (Kirmse and Rode, 1986 Kirmse et al., 1986 a) demonstrated that A-nitroso carbamates are preferable to A-nitroso amides because of higher yields in the nitrosa-tion step. In the synthesis of A-[l-(3-hydroxypropyl)cyclopropyl] acetamide (7.17) Kirmse and Rode (1987 b) found that primary nitrosation takes place at the hydroxy group, and N-nitrosation was achieved only after complete O-nitrosation. 

Recently, White et al. (1992 a) showed that A-nitroso sulfamates (7.18), a class of compounds related to A-nitroso amides, can be used for the generation of diazonium ions in aqueous buffers at pH 2, i. e., in an acidity range where direct nitrosation of aliphatic amines is very slow. 

N-Nitroso amides can also be used for the formation of alkyldiazenolates (7.9) by bases. Alkyldiazenolates can be isolated from aprotic solvents as alkali metal salts, as found by Hantzsch and Lehmann (1902). More modern procedures have been described by Tandy and Jones (1965) and by Moss (1966). One obtaines the (Z)-diazenolate, as confirmed by X-ray analysis (Muller et al., 1963). From Scheme 7-3, one might assume that the route starting with diazenolates will lead to the same products as the nitrosation of alkylamines because the diazenol is common for both pathways. 

In a second paper, Streitwieser and Schaeffer (1957 b) used the same sample of [l- H]butylamine for the A nitroso amide method of deamination in acetic acid and found complete racemization. They rationalized this result by assuming the formation of 1-diazobutane as an intermediate, as shown in (7-15). Although a repetition of this process, but using the NMR method for stereochemical analysis, is not likely to give a substantially different result, it would be welcome for clarification. 

Maskill and Whiting s investigation is of general interest it allows comparison of yields in the ten reactions. Dediazoniation via triazenes (7.91 and 7.92) gives very good yields 93-99% (cis) and 77-85% (trans) via nitroso amides (7.93 and 7.94) 55 % (cis) and 75-84% (trans) are reported. Direct deamination yields are low, as expected (18% for cis, 14% for trans). Nevertheless, it is interesting to note that the yields in ra-deamination can be doubled (37%) when the reaction is conducted under nitrogen. ... 

The last-mentioned disadvantage of deaminations of amines with nitrosating compounds in aqueous and other protic solvents is, of course, not present if N-nitroso amides and related compounds discussed earlier (7.10, and footnote on p. 246, concerning White s pioneering work) are used in aprotic solvents. 

In conclusion, we propose a specific research program for deaminations in aqueous systems based on ideas mentioned in this section, namely to investigate (a) deamination kinetics and products of a series of simple aliphatic amines in water with sodium nitrite and perchloric acid at various acidities, (b) decompositions of diazenolates of the same amines in water and (c) decompositions of a standard type of N-nitroso amides, again of the same amines and all in the same aprotic solvent. The reaction conditions should be as similar as possible in the experiments of all three series. The series of amines should include methyl-, ethyl-, 1-methylethyl-, 1-methylpropyl-, and ( cr butyl)amine and [l- H]ethylamine, but not amines with longer aliphatic chains, as the very informative work of Southam and Whiting (1982) demonstrated clearly that, in deaminations of such amines, many mechanistically complex products are formed. In addition, micellar effects increase the complexity of reactions with such amines (see Sect. 7.3). It is obvious from the series of amines that we have proposed that this program is based on the work of Brosch and Kirmse (1991), Hovinen and Fishbein (1992), Hovinen et al. (1992), Finneman et al. (1993), and Ho and Fishbein (1994). Work with chiral 1-methylpropyl- and [l- H]ethyl-amine will provide information on the stereochemistry of these reactions. 

Investigations with N-nitroso amides and related N-nitroso compounds have the advantage that many difficulties with combined nitrosation and dediazoniation processes (as discussed above) can be avoided. Their results cannot, however, always be applied for an understanding and improvement of the most classical deamination method, i. e., the hydroxy-de-amination of an amine in an aqueous nitrosation. 

The analogous reaction of an aromatic iV-nitroso amide (7V-nitrosoacetanilide) with benzene forming biphenyl was discovered by Bamberger in 1897. 

Before we close this section, it should be mentioned that rhodium catalysts were added by Godfrey and Ganem (1990) to solutions of A-nitroso amides and they observed that the same products were obtained as with diazo compounds. This is, of course, not surprising, as diazo compounds are intermediates in the decomposition of A-nitroso amides. Yet, it is remarkable that, to the best of our knowledge, this method has not been investigated more frequently. 

---