Properties of diazirines

Diazirines, carbene precursors, have slowly gained in importance since Smith and Knowles (1973, 1975) first made 3-H-3-aryIdiazirines and suggested that they would make useful reagents. Three useful classes of diazirines are given in Table 3.1. 

---

The absorption properties of diazirines are characteristic. All possess an absorption band in the near ultraviolet (kmax 350 to 380 nm) which is resolved into a series of sharp peaks in non-polar solvents such as hexane. Extinction coefficients are modest, usually around 300 M-1 cm-1, but... 

In the last decade, limited research has been published on the thermodynamic properties of diazirines and diaziridines. Extensive coverage of this topic was presented in CHEC-II(1996) <1996CHEC-II(1A)347>. 

Aryl-1 -fluorocyclopropanes 2 were synthesized by irradiation of a 3-aryl-3-fluoro-3//-diazirine and an alkene (2 > 300 nm, 25 °C) in a screw-top Pyrex Carius tube (Houben-Weyl, Vol. E19b, p980). The starting 3-aryt-3-fluoro-3//-diazirines were prepared from the corresponding 3-aryl-3-bromo-3//-diazirines and anhydrous tetrabutylammonium fluoride. The products were purified by column chromatography on silica gel (purity > 97%). Due to the explosive properties of diazirines, this method is not suitable for large-scale preparations. 

The properties of the diazirines and the analytical results showed that a new class of isomeric diazo compounds had been discovered. The three-membered ring structure (65), which is made probable by the synthetic methods, is confirmed by the reactions of the diazirines. 

In an attempt to reduce the size of the photoreactive group, Emi and Khorana (1980) investigated the properties of tetrafluorodialkyl diazirines. Unfortunately these compact molecules (Fig. 3.17) did not yield insertion products on photolysis, but rearranged internally by alkyl migration to give olefins, and underwent intramolecular insertion to yield cyclopropanes. 

Brunner et al. (1980) have reported on the properties of a new class of aryl diazirines, the 3-aryl-3-trifluoromethyldiazirines. Besides forming a class of the most attractive photoactivatable reagents available, these molecules may be made in far higher yield than the corresponding 3-H-diazirines. The route used, which incidentally fails with the 3-H-com-pounds (Smith and Knowles, 1975), is shown in Fig. 3.24. Two drawbacks are the large number of steps involved and the difficulty of preparing... 

It should be pointed out that despite their high reactivity carbenes are selective, and while they will react with hydrocarbons in the absence of nucleophiles, a nucleophilic group exposed within the bilayer will preferentially be attacked. Some properties of the three most thoroughly tested reagents iodonaphthyl azide, adamantane diazirine, and 3-trifluoromethyl-3-(m-iodophenyl)diazirine are summarized in Table 6.1. There follows a brief description of a typical experimental procedure, a discussion of control experiments, and several caveats, followed by some examples of the applications of hydrophobic reagents. 

Diazirines are a reliable source of carbenes, and this property has dominated their application in the last decade. In particular, there has been considerable use of diazirines in macromolecular systems, both chemical and biological, and this is the subject of a recent review <2005SFM178>. Synthetic applications are documented in Section 1.11.6. 

The adducts 9 of arylchlorocarbenes, generated thermally or photolytically from the corresponding diazirines, to electrophilic alkenes have also been prepared the physical properties of these cyclopropanes were not reported. 

The diazirine method allows the electronic properties of organo(organooxy)carbenes to be characterized. 

Aryl(methoxy)carbenes, generated photolytically from 3-aryl-3-methoxy-3//-diazirines, underwent addition to 1,1-dimethylallene to give methylenecyclopropane derivatives 1 (no yields or physical properties of the products were reported). ... 

Derivatives of Cgo for photoaffinity labelling studies have been synthesized, including the cis and treats diazirine compounds (21a). The photochemical properties of these are currently being studied in various applications. An... 

The diazirines are of special interest because of their isomerism with the aliphatic diazo compounds. The diazirines show considerable differences in their properties from the aliphatic diazo compounds, except in their explosive nature. The compounds 3-methyl-3-ethyl-diazirine and 3,3-diethyldiazirine prepared by Paulsen detonated on shock and on heating. Small quantities of 3,3-pentamethylenediazirine (68) can be distilled at normal pressures (bp 109°C). On overheating, explosion followed. 3-n-Propyldiazirine exploded on attempts to distil it a little above room temperature. 3-Methyldiazirine is stable as a gas, but on attempting to condense ca. 100 mg for vapor pressure measurements, it detonated with complete destruction of the apparatus." Diazirine (67) decomposed at once when a sample which had been condensed in dry ice was taken out of the cold trap. Work with the lower molecular weight diazirines in condensed phases should therefore be avoided. 

---