Diazotization of aliphatic amines

For reviews of rearrangements arising from diazotization of aliphatic amines, see, in Patai The Chemistry of the Amino Group Wiley NY, 1968, the articles by White, E.H. ... 

One might expect that diazotization of aliphatic amines under alkaline conditions or in the presence of strong proton acceptors used for general base catalysis might also yield diazoalkanes. This alternative route, however, has not been successful so far, as shown by the experiments of Maltz et al. (1971), who nitrosated amines with disodium pentacyanonitrosyl ferrate (Fe[CN]5NO Na2 ) at pH up to 12.7 (see Sect. 2.3). 

Friedman, L., and J. H. Bayless Aprotic Diazotization of Aliphatic Amines. Hydrocarbon Products and Reaction Parameters. J. Amer. Chem. Soc. 91, 1790... 

Although Hammett convincingly explained the nitrosation of aliphatic amines and the diazotization of aniline under the conditions employed by Schmid and others, one unsatisfactory point remained namely the second-order kinetic equation obtained by Hantzsch and the workers who followed him for diazotization in a more weakly acidic medium. Comparison of experimental details shows that at concentrations of free mineral acid below 0.05 m the reaction is apparently second-order, but it becomes third-order at higher concentrations of acid. 

As the proton release is often too slow under the acidic conditions used for the diazotization of aromatic amines, syntheses of aliphatic diazo compounds by this method are carried out without an excess of mineral acid. Usually, equimolar amounts of amine, HCl and NaN02, or amine and NOCl, are used. A better alternative is nitrosation with pentyl nitrite in the presence of up to 30% acetic acid, as found by Takamura et al. (1975). Yields higher than 60% were obtained with a-amino-substituted esters of some aliphatic carboxylic acids. 

An azo coupling reaction of primary aromatic and aliphatic amines with diazotized 4-nitroaniline in water-organic solutions has been investigated. It has been demonstrated that depending on the nature of an organic solvent different azo derivatives are formed in neutral medium. 

It is worth noting, however, that the prototropic equilibrium between the N-nitrosoamine (3.7) and the diazohydroxide (3.9) has been determined semiquan-titatively for the analogous diazotization of an aliphatic amine. Fishbein and coworkers (Hovinen et al., 1992) determined an upper limit for the nitrosoamine equilibrium concentration (<1.5% see also Zollinger, 1995, Sec. 7.2). 

Diazonium ions generated from ordinary aliphatic primary amines are usually useless for preparative purposes, since they lead to a mixture of products giving not only substitution by any nucleophile present, but also elimination and rearrangements if the substrate permits. For example, diazotization of n-butylamine gave 25% 1-butanol, 5.2% 1-Chlorobutane, 13.2% 2-butanol, 36.5% butenes (consisting of 71% 1-butene, 20% trans-2-butene, and 9% cw-2-butene), and traces of butyl nitrites. ... 

For aromatic amines, the reaction is very general. Halogen, nitro, alkyl, aldehyde, sulfonic acid, and so on, groups do not interfere. Since aliphatic amines do not react with nitrous acid below a pH of 3, it is even possible, by working at a pH of 1, to diazotize an aromatic amine without disturbing an aliphatic amino group in the same molecule. ... 

Despite the fact that diazotization takes place in acid solution, the actual species attacked is not the salt of the amine, but the small amount of free amine present. It is because aliphatic amines are stronger bases than aromatic ones that at pH values below 3 there is not enough free amine present for the former to be diazotized, while the latter still undergo the reaction. In dilute acid the actual attacking species is N2O3, which acts as a carrier of NO. Evidence is that the reaction is second order... 

The intermediates resulting from the diazotization of primary, aliphatic amines are unstable they are rapidly converted into carbocations after loss of nitrogen, and yield products derived from substitution, elimination or rearrangement processes. 

Answer By diazotization of B via procedure X1M. Note that it is possible to diazotizc an aromatic amine in the presence of an aliphatic amine provided the pH of the solution is kept below 3. 

Aliphatic amines can also be diazotized, but the products are too unstable to be isolated and rapidly evolve nitrogen gas. The relative stability of aromatic diazonium salts is a result of delocalization of the positive charge on nitrogen into the 7i-system of the ring, as illustrated by the canonical forms 16-18. 

Secondary aliphatic amines form stable N-nitrosoamines, however, and therefore, their investigation will be discussed briefly in this section, although N-nitroso derivatives of secondary aliphatic amines do not fall within the scope of this book. We will see that kinetics and mechanisms of nitrosation of secondary amines display many similarities with the diazotization of primary aromatic amines. 

Catalysis by other nucleophiles has also been found for secondary aliphatic amines, e. g., by thiocyanate (Fan and Tannenbaum, 1973), and by thiourea and its tetramethyl derivative (Meyer and Williams, 1988, and earlier investigations mentioned there). The results are comparable to those of aromatic diazotizations (Zollinger, 1994, Sect. 3.3). 

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 discussed in Chapter 2, diazotization of primary aliphatic amines generally does not lead to diazoalkanes, because the intermediate alkanediazonium ion loses the diazonio group faster than a proton of the C(a)-atom. Diazoalkane formation is dominant if the deprotonation rate is increased by acidifying substituents in the a-position (see Sect. 2.3). Curtius synthesis of ethyl diazoacetate (1883) is the classical example. Hart and Brewbaker (1969) showed clearly that acidifying substituents favor diazoalkane formation over dediazoniation electron-donating substituents exert the opposite effect. 

Several readers of this section would be disappointed that not more mechanistic results that can certainly be found in the literature are discussed here. There is no doubt that there are investigations of good quality, but in most cases it is my feeling that they are useful and interesting only within the limits of the specific reaction or structure involved, but not for a broader scientific context. This is the reason for the brief character of this section. It demonstrates a very significant difference in the mechanisms of diazotization of aromatic and aliphatic primary amines ... 

As mentioned in Section 1.1, the first diazotization of amines, followed by dediazoniation, was carried out by Piria in 1848, well before Griess discovered and isolated aromatic diazo compounds (1858). Piria added an impure HNO3 —HCl solution to a mixture of asparagine and aspartic acid in water and obtained malic acid (7-1). It was not possible for Piria, however, to realize that the primary reaction products were diazonium ions. Yet, Piria s process was one of the few types of reaction via aliphatic diazonium ions that became important for synthetic purposes, after Ingold s group (Brewster et al., 1950) discovered that a-amino acids undergo clean retentive deamination (see Sect. 7.7). 

A] Diazotization Reactions. There exists a marked and pronounced difference between the aliphatic amines and the primary aromatic amines whereby the former reacts with cold aqueous nitrous acid (HNOg) to give rise to the formation of the corresponding primary alcohol as the major product of reaction and the latter under identical experimental parameters exclusively results into the formation of benzenediazonium chloride (salt), sometimes also termed as diazo-benzene chloride as illustrated below ... 

What is the major difference between diazotization of an aliphatic amine and an aromatic primary amine ... 

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