Azide phosphine reaction

The important compounds of nitrogen with hydrogen are ammonia, Irydrazine, and hydrazoic acid, the parent of the shock-sensitive azides. Phosphine forms neutral solutions in water reaction of phosphorous halides with water produces oxoacids without change in oxidation number. 

In a number of ways the reactions of stable silylenes resemble those of phosphines, R3P, to which they are isolobal analogs. Examples are provided by the reactions of 59 with covalent azides. Phosphines are known to react with azides to give phosphineimines, Ph3P=NR. In similar fashion, 59 reacted with triphenylmethyl azide in THF to give the silanimine 72 as its THF complex (equation 109)148. This reaction provides a new method for synthesizing compounds containing Si=N double bonds, which have previously been made by salt elimination reactions375. 

Denmark, S. E., Dorow, R. L. The stereochemical course of migration from phosphorus to nitrogen in the photo-Curtius rearrangement of phosphinic azides (Harger reaction). J. Org. Chern. 1989, 54, 5-6. 

The reactions with hydrogen cyanide, hydrazoic acid, phosphines, and arsines (Section 16.5) have been used as routes to the organotin cyanides, azides, phosphines and arsines, respectively. Examples are given in the following equations.29... 

The reaction of a large number of other nucleophiles with iminium salts will at least be mentioned in this section. Among the nucleophiles which react with iminium salts are cyanide 48,115-119), mercaptide 48), alkoxide 48), amine 120), azide 44), phosphine 44), and phosphate ester 44). One can say with little reservation that almost all nucleophiles will react... 

The nucleophilic displacement reactions with azide, primary amines, thiols and carboxylatc salts arc reported to be highly efficient giving high (>95%) yields of the displacement product (Table 9.25). The latter two reactions are carried out in the presence of a base (DBU, DABCO). Radical-induced reduction with tin hydrides is quantitative. The displacement reaction with phenolates,61j phosphines,6M and potassium phthalimide608 gives elimination of HBr as a side reaction. 

A similar microwave-assisted cyclization in the presence of ammonium acetate of an a-ketoamide, obtained by acylation of an a-aminoketone, was recently described for the synthesis of the antifungal agent Nortopsedin D [46]. The problem of the instabiUty of the a-amino ketones was successfully resolved by in situ acylation of the amine derived from Staudinger reaction of the azide 50 with a phosphine (Scheme 16). This ketoamide was... 

A convenient aziridine synthesis using 2-iodoalkyl azides and triphenyl-phosphine has been reported. The reaction is stereospecific and is thought to proceed by attack of the phosphine on azide ... 

Aryldioxophosphoranes such as aryl- and alkyl-iminooxophosphoranes number among the short-lived metaphosphonates. The former are best obtained by fragmentation of cyclic phosphinic esters, and the latter by rearrangement of aryl- and alkyl-substituted phosphoryl azides and nitrenes, respectively. This reaction is reminiscent of the phosphorylcarbene/methyleneoxophosphorane rearrangement discussed in Section 2. 

In general, azides are more easily available than nitro compounds by SN2 reaction of the corresponding halides. Thus, the direct conversion of an azide into a nitro group is useful for the synthesis of nitro compounds. Corey and coworkers have reported the easy conversion of azides to nitro compounds via ozonolysis of phosphine imines (Eq. 2.70).139... 

Hydroxymethyl phosphines are susceptible to oxidation to form the phosphine oxide derivative. Therefore, avoid excess oxygen, oxidizing agents, or azide compounds, which react with phosphines in the Staudinger reaction (Chapter 17, Section 5). In addition, metallic surfaces can be modified via the phosphine group to result in hydroxymethyl group substitutions. 

Early in the last century, the Nobel Prize winning chemist Hermann Staudinger discovered a reaction between phosphines and azides, which became known as the Staudinger reaction (Staudinger and Meyer, 1919). Triphenylphosphine reacts with azides to form an intermediate iminophosphorane with the release of nitrogen gas. This intermediate quickly breaks down in aqueous environments to yield triphenylphosphine oxide and a primary amine (Figure 17.17). 

Figure 17.17 The Staudinger reaction involves the reduction of an azide to a primary amine with loss of N2 and the concomitant oxidation of a phosphine derivative to a phosphine oxide.

Figure 17.18 The Staudinger ligation reaction uses a modified phosphine derivative containing an electrophilic group that acts as a trap for the nucleophilic nitrogen in the intermediate aza-ylide. The resultant shift yields an amide bond derivative between the phosphine-containing molecule and the azide-containing molecule.

There now are available a number of alkyl azide compounds that may be used in click chemistry reactions and the Staudinger ligation processes. It is not recommended, however, to use aryl azide compounds, as these are light sensitive and photoreactive as well as highly susceptible to reduction in the presence of thiols. Unfortunately, at the time of this writing there are fewer choices in aryl phosphine compounds to participate in this reaction, as commercial sources of labeling reagents are limited. 

The methods used for in vivo incorporation of azido-monomers and performing a labeling reaction with live cells are relatively simple. The following protocol is based on the methods of Saxon and Bertozzi (2000), which uses acetylated azidoacetylmannosamine as the azido-monomer source and a biotin-PEG-phosphine compound to biotinylate cell surface glycoproteins at the specific azide-sialic acid incorporation sites (Figure 17.19). 

Figure 17.20 An azido-palmitic acid derivative can be added to cells to obtain palmitoylated proteins that contain an azide group able to participate in the Staudinger ligation reaction. Biotinylation of these post-translationally modified sites then can be done in vivo using a biotin-phosphine reagent.

---