Azide transfer reagents

Figure 28.14 A trifunctional label transfer reagent containing a thiol-reactive pyridyl disulfide group, a photo-reactive phenyl azide, and a biotin affinity tag. This compound can be used to label bait proteins through available thiol groups and capture interacting prey proteins by photoreactive conjugation.

Figure 28.15 Two similar label transfer reagents containing a thiol-reactive methanethiolsulfonate group to label bait protein through available sulfhydryls, a tetrafluorophenyl azide group for high-efficiency photoreac-tive conjugation with interacting prey proteins, and a long biotin affinity tag.

What happens to that second molecule of diazomethane By collecting a proton it turns into the very reactive diazonium salt, which collects a chloride ion, and MeCl is given off as a gas. The second method uses tosyl azide, which is known as a diazo transfer reagent—it s just N2 attached to a good leaving fcroup. 

Caution Although the mixture of dodecylbenzenesulfonyl azides is the safest of a group of diazo transfer reagents,2 one should keep in mind the inherent instability, shock sensitivity, and explosive power of azides. All users should exercise appropriate caution. 

Alkali metal azides react with epoxides in a appropriate solvent to give vicinal azidohydrins. Phase-transfer reagents may be used. The reactions usually require high temperatures and/or long reaction times. 

Green, G. M., Peet, N. P., Metz, W. A. Polystyrene-Supported Benzenesulfonyl Azide A Diazo Transfer Reagent That Is Both Efficient and Safe. J. Org. Chem. 2001, 66, 2509-2511. 

Naphthalenylsulphonyl azide has been advocated as a diazo transfer reagent of a capability superior to that of/ -toluenesulphonyl azide s. 

In diazo transfer reactions both N-atoms, i. e., the entire diazo group, are introduced into a suitable substrate from a diazo donor (2-46). In most cases this transfer reagent is a sulfonyl azide (Y=N2 = Ar-S02N=N2 or R-S02-N=N2), from which the N(yff)- and N(y)-atoms will form the diazo group in the product. There are, however, also cases in which the diazo group of an aromatic diazonium ion or of a diazoalkene is transferred. Such examples are of minor importance. 

The advantage of methanesulfonyl azide (mesyl azide) is that it is easily separated from the desired product by washing the organic phase (CH3CN or ether) with 1097o aqueous NaOH solution. Other transfer reagents are either more expensive or show similar disadvantages to those of 4-toluenesulfonyl azide (see Taber et al., 1986, references 5 and 6). Since 1985, Taber (1989) prefers mesyl azide to 4-toluenesulfonyl azide in all diazo transfers. 

Polymer-bound arylsulfonyl azides have been tested as diazo transfer reagents (Roush et al., 1974 Diirr et al., 1981). Yields with diethyl malonate and acetylace-tone are slightly lower than those with 4-toluenesulfonyl azide. In contrast to these compounds with two neighboring activating groups, yields with monoactivated methylenes (ethyl propionate and cyclohexanone) are much lower. This method is therefore, not recommended in the described form. 

The results discussed above clearly demonstrated that the cleavage of the dihydrotriazole ring to diazoalkane products following Scheme 2-67 is facilitated most by 4-toluenesulfonyl azide, although, in some cases, diazoalkanes can also be obtained with other aryl azides. Unfortunately, no study has been conducted comparing reactivity, products, and the yields of reactions with methanesulfonyl azide. This transfer reagent was recommended by Taber et al. (1986, see Sect. 2.6) as a superior reagent to 4-toluenesulfonyl azide. 

If cyanogen azide or 2-azido-3-ethylbenzothiazolium tetrafluoroborate is used as diazo transfer reagent, only the diazoamidines are detected (Regitz et al., 1981a). This is consistent with the interpretation of the results of Table 2-3. 

For acceptor-substituted alkynes, it is possible to use trimethylsilyl azide as transfer reagent (cyanogen azide does not react). The reaction (2-90) is not regiospecific, but the silylated triazoles 2.225 can be hydrolyzed and deprotonated to the anion 2.226. The latter reacts regiospecifically with cyanogen bromide to form the triazole-carbonitrile 2.227, which is in equilibrium with the a-diazo-A -cy-ano-imine 2.228 (Regitz et al., 1981 b). 

Azide transfer to 3-deoxyglycak. This explosive-prone reagent is prepared in situ... 

The synthesis of S-N-azido derivatives of N-acetylneuraminic acid has been accomplished by both enzymatic and chemical methods. In particular, SchmidP and Wong described the introduction of the azido group from known sialosyl donors 11a and 11b respectively by using trifluoromethanesulfonyl azide (triflic azide, TfNs) as the diazo transferring reagent (Scheme 3). 

Benzenesulfonyl azide transfers its azido function to Grignard reagents (164). The soft reagents do not attack the hard sulfonyl group. 

The direct diazo transfer from sulfonyl azides to methyl ketones is usually not a practicable process, with the exception of the a-diazotization of ketones with 2,4,6-triisopropylbenzenesulfonyl azide under phase-transfer conditions. However, diazomethyl ketones amenable to the Arndt-Eistert reaction can be easily prepared in two steps by a formylation-deformylation diazo-transfer sequence (Regitz procedure ). A related practical method advantageously applies the detrifluoroacetylation of a-trifluoroacetyl ketones tScheme 3 a). The preparation of 2-diazo-1,3-dicarbonyl compounds is commonly best performed with p-toluenesulfonyl azide (TsNg) as the diazo-transfer reagent tScheme 3.9h). > An issue... 

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