Alkyl nitrite as reagent

In most cases diazonium salts are not isolated, but are converted into products by reactions that can be carried out in situ. Moreover, it is actually recommended not to isolate these salts, not even for purification purposes, as many of them have a tendency to explode. In addition, the high solubility of most diazonium salts in water makes precipitation from this medium difficult. Therefore, to obtain solid diazonium salts the recommended method for many decades was to carry out diazotizations in ethanol followed by precipitation with ether. As inorganic salts of nitrous acid are scarely soluble in ethanol, Knoevenagel recommended alkyl nitrites (ethyl or isopentyl nitrite) as diazotization reagents as long ago as 1890. Various other solvents have subsequently been used for diazotizations with alkyl nitrites (see Saunders and Allen, 1985, p. 23 ff.), but as a method for obtaining solid diazonium salts this has been superseded by the isolation of diazonium tetrafluoroborates and, to a lesser degree, of hexafluorophosphates. 

HF—Amine Complexes Complexes of fluorhydric acid (HF) with pyridine or alkyl amines (Et3N, Et2NH) are often utilized as reagents in nucleophilic fluorination reactions such as the opening of oxiranes," the bromofluorination of double bonds in the presence of NBS, or the diazotation/fluorination of amines with sodium nitrite (the Balz-Schiemann-like reaction) (Figure 2.1). ... 

As indicated above, tertiary aromatic amines are directly C-nitrosated. The usual reagents are sodium nitrite and dilute hydrochloric acid, sodium nitrite and glacial acetic acid containing concentrated hydrochloric acid, and nitrite esters with hydrochloric acid [21a, 27]. While tertiary amines with such complex alkyl groups as found in A,A-di(3,5,5-trimethylhexyl)aniline are readily nitrosated [25], of the four A-butyl-A-methylaniline isomers, JV-r-butyl-A-methylaniline does not undergo the reaction, and even the nitroso compounds which did form were only unstable oils [27]. 

The thiazolyl radicals are, in comparison to the phenyl radical, electrophilic as shown by isomer ratios obtained in reaction with different aromatic and heteroaromatic compounds. Sources of thiazolyl radicals are few the corresponding peroxide and 2-thiazolylhydrazine (202, 209, 210) (see Table III-34) are convenient reagents, and it is the reaction of an alkyl nitrite (isoamyl) on the corresponding (2-, 4-, or 5-) amine that is most commonly used to produce thiazolyl radicals (203-206). The yields of substituted thiazole are around 40%. These results are summarized in Tables III-35 and ni-36. 

The first A-acylannino acid azides were synthesized according to procedures developed by Curtius.01 The reactions were carried out under acidic conditions, such as aqueous acetic acid, hydrochloric add or mixtures of both. Low temperature solutions of sodium nitrite were used as oxidizing agents.h l These older procedures have been comprehensively de-scribedh and are presently used mainly in the preparation of reagents like Boc-Nj (see Section 2.1.1). Since the sodium nitrite procedure when applied to peptide hydrazides, is cumbersome and readily accompanied by side reactions, alternative methods were developed by Honzl and Rudinger which are based on the use of alkyl nitrites. With these... 

More recently another modification for the preparation of peptide azides was introduced by Alfeeva et al-f l using tetrabutylammonium nitrite as auxiliary reagent. In contrast to the alkyl nitrites which are relatively unstable and therefore have to be purified prior to use by distillation, tetrabutylammonium nitrite is a crystalline and stable compound, which is soluble in anhydrous dipolar aprotic solvents. Moreover, in this procedure the acidity of the reaction mixture is adjusted with anhydrous p-toluenesulfonic acid instead of HCl in anhydrous organic solvents. These conditions are experimentally convenient and more easily controlled than those of the Honzl-Rudinger method. Comparative model reactions performed with ferf-butyl nitrite and tetrabutylammonium nitrite produced nearly identical peptide yields. To date, there are no reports of the condensation of larger fragments and peptide cyclization by this azide procedure. 

Propyl nitrite has been shown to be a poor reagent for nitrosation of aniline derivatives, but the reaction can be catalysed by halide ions the probable mechanism involves rapid equilibrium formation of the nitrosyl halide, which then reacts with aniline. A similar mechanism has been proposed when alkyl nitrites and titanium tetrahalides are used as a nitrosating reagent. ... 

Nitrosyl halides, particularly NOCl and NOBr, can also be used as diazotization reagents undo" anhydrous conditions, as these gases (NOCl mp —59.6°C, bp —6.4°C NOBr bp 0°C) are readily soluble in many organic solvents. They can also be generated in situ in chlorinated hydrocarbons by reaction of trimethylsilyl halides with alkyl nitrites (equation 13) as shown by Weiss and Wagner . The group of Weiss found also that NW-bissUylated anilines react in aprotic dichloromethane with generation of diazonium salts and formation of the nonnucleophilic hexamethyldisiloxane (equation 14). 

Before we talk about this group of aromatic Sfjl reactions in more detail, let s consider how to make the diazonium salt. The reagent we need is the reactive nitrogen electrophile NO. You met NO in Chapter 20, but to remind you, it forms when the nitrite anion (usually sodium nitrite) is treated with acid at around 0 °C. Protonation of nitrite gives nitrous acid, HONO protonation again gives a cation, which can lose water to form NO. Butyl nitrite (or other alkyl nitrites) can also be used as a source of NO. ... 

The triazene T1 linker has been successfully used as a linker for arenes. Up to now, more than 100 different anilines have been immobilized by the Erase group and others [234,235]. In general, the synthesis starts with diazota-tion of an aniline derivative in an organic solvent using alkyl nitrite reagents. The immobilization on solid supports has been successfully carried out using... 

Selective denitration of methyl 4,6-O-benzylidene- and 4,6-O-alkyl-idene-D-hexopyranoside 2,3-dinitrates to yield 3-nitrates has also been achieved by using sodium nitrite in ethanol as the reagent.233,238, 241.242 interestingly, when the nitrate group is on a primary carbon atom, reaction with this reagent takes place to give the primary alcohol,232,241,243 but the conversion may, on occasion, proceed only with... 

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