Chemistry Reference
In-Depth Information
been studied by means of laser transient spectroscopy. Some of these include
8-azido-8-methoxypsoralen
27,42
and 2-azido-1-methylimidazole.
28
During this
same period, Platz investigated a series of fluorinated phenyl azides including
perfluorophenyl azide and a series of 4-substituted tetrafluorophenyl azides.
43
Nitrenium ions could be observed in these fluorinated systems, if irradiations
were conducted in dilute aqueous solutions of sulfuric acid to aid in the protonation
of the nitrenes. Unfortunately, no products could be isolated from these reactions as
the nitrenium ions apparently polymerized.
The next generation of ultrafast laser transient spectroscopy has made it possible
to visualize the extremely rapid events that were obscured by the long-probe laser
pulses in the previous studies. Platz, Burdzinski, and Bally have examined unadorned
polycyclic aryl nitrenes and observed them to undergo protonation to form nitrenium
ions, but in order for protonation to be competitive with intersystem crossing to the
triplet, the nitrenes must be generated in acidic solvents. Thus, the following singlet
nitrene lifetimes were observed when the nitrenes were generated in 88% formic
acid: 1-napthtyl nitrene,
8.4 ps
48
;
p
-biphenylyl nitrene,
11.5 ps
48
; phenyl
t ¼
t ¼
10 ps.
50
Much
less rapid protonation occurs in alcoholic solvents, for example, in methanol, where
2-fluorenyl nitrene has a lifetime of
12.0 ps (100% formic acid)
49
; and 2-fluorenyl nitrene,
nitrene,
t ¼
t ¼
250 ps.
50
The valuable information gleaned from these transient studies was that, if properly
substituted, aryl nitrenes are surprisingly strong bases that can abstract protons from
water without the aid of added acid. In order for the nitrenium ion-forming branch of
aryl nitrene chemistry to be favored over the ring-expansion branch in Scheme 3.7,
the nitrene must be conjugated to strong electron-donating groups or extended
p
t ¼
-systems. Detailed theoretical studies of phenyl azides substituted in the
para
position with a wide variety of substituents reinforces the observation that
para
-
electron-donating groups greatly stabilize the singlet state of nitrenium ions.
51
The
nitrenium ion pairs that result from protonation of these nitrenes are surprisingly
stable and do not collapse quickly, as might be expected, but survive into the
microsecond and even millisecond time domains. Furthermore, the mode of collapse
observed in these early studies was nucleophilic attack of water at the
para
position,
which results in hydrolysis to a quinone with loss of the original aryl azide
substituents (Scheme 3.8).
Many of these properties of aryl nitrenium ion are not particularly favorable for
development of photoaffinity-labeling systems. Thus, an ideal photoaffinity label
will form a strong covalent bond with neighboring molecules, and this bond must
survive isolation and analysis. As can be seen from the aforementioned examples, the
ketenimine branch affords cross-linking bonds that are easily broken by hydrolysis,
Scheme 3.7, and the nitrenium ion branch often does the same. In addition, while the
nitrenium ion pair is formed very rapidly, it collapses to form the pivotal cross-
linking bond very slowly in the micro- to millisecond time domain. So information
about specific binding sites derived from such slowly formed cross-links may be
spurious.
Some of these problems can be circumvented through the modification of the aryl
azide system as shown in Scheme 3.9. Thus, the PAL agent might be attached to the
