J.N. Abrams
Tetrahedron xxx (xxxx) xxx
of reactivity within several seconds marked by gas evolution and
reaction darkening. The gas bubbling does not subside until after
the carbonate/carboxylate addition has completed. As well, ac-
cording to TLC analysis there is unnoticeable reaction conversion
after the completion of this addition. The reaction does not appear
to be intolerant to oxygen.
Continued investigation of the generality of this methodology
and its refinement together with the unraveling of the critical
mechanistic details of this process may enable its application to-
wards triazenes that present synthetic challenges, and pave the
way for this methodology's application in related transformations
as well.
Scheme 15. Triazenes via Outer-Sphere ET.
This scenario is regarded as being the most likely in Doyle's DMF
promoted hydrodediazoniation of in situ generated diazonium salts
[ 30].
2.1. Cautionary statements
As the release concomitantly of CO and Hþ occurs regardless of
carbonate in this current investigation's reaction system seems to
serve a critical role as buffer against developing reaction acidity. As
well, the reaction progress may be facilitated in part by conversion
of the generated carbonic acid, formed during this neutralization,
into water and CO2, which according to Le Chatelier's Principle
drives the reaction towards completion. This may account for the
significantly reduced requirement of working reaction tempera-
ture, observable even between 25 and 30 ꢂC, when compared with
Markgraf's investigation [32]. The cesium carbonate may further-
more play an influential role in dictating the nature of in-
termediates in play, as diazonium chemistry is known to be
sensitive to reaction pH as previously described [36].
Diazonium salt handling in the laboratory requires precaution-
ary measures [3b,56] because these species are heat and shock
sensitive. Nevertheless, the tetrafluoroborate counterions usually
impart sufficient stability to render acceptability to all of the non-
heterocyclic aromatic compounds [57] that have been used in this
and our previous work [26].
2.2. General procedure
The reaction setup does not require any elaborate manipula-
tions, and all materials are sufficiently handled. This reaction pro-
cedure first involves the generation of a homogeneous methanolic
solution of cesium phenyl propiolate salt or simply a methanolic
solution of cesium carbonate. In either case cesium carbonate is
quickly charged into a round bottom flask under Schlenk conditions
due to its modest hygroscopic nature and either combined with
phenyl propiolic acid or left as is before addition of methanol. In
both circumstances the methanolic mixture reaches complete
dissolution after a period of about 1 h at room temperature. Next,
dropwise addition of this newly generated homogeneous ca. 0.2 M
anhydrous methanolic solution to a ca. 0.2 M anhydrous DMF so-
lution of diazonium salt that had been heated to 50e60 ꢂC occurs
over the course of several minutes. Gas evolution is noted, as
indicated by some reaction bubbling, eventually subsiding after the
dropwise addition is completed. Nevertheless subsequent stirring
at this temperature commences for a period of a few hours, akin to
the work of Doyle. As another indicator of reaction progress, the
reaction darkens significantly during the time course of the drop-
wise addition, turning from usually a pale yellow color initially to a
reddish hue, and then to a very dark purple tone.
1.10. Work most closely resembling this methodology
The working conditions of Markgraf et al. [32]. most closely
resemble those employed in this current investigation. Markgraf
also utilized an isolated diazonium tetrafluoroborate salt that was
dissolved in DMF. His work however required high heating of up to
100 ꢂC over a 2 h period en route to mainly protodediazonized
product along with a sparing amount of one triazene product,
observed apparently in about 10% yield. No other procedure that I
am aware of stipulates a triazene product generation via a method
of this nature. Clearly the diazonium salt activation in this current
study, by dropwise addition of carbonates or carboxylates, is an
important feature change that has enabled reactions to take place
even at room temperature. Complete consumption of diazonium
salt occurs within minutes.
Likewise, the reaction workup is performed in a simple fashion
by first adding a small portion of Amberlyst 15 DRY to the crude
mixture until affording a mildly acidic pH (ca. 6) as observed by
litmus paper. Second, gravity or vacuum filtration is performed to
remove spent ion exchange resins. Finally, crude product isolation
is completed via rotovap concentration. Residual DMF is removed
via azeotropic distillation with small amounts of added toluene.
The concentrated crude products are then subjected to flash
chromatographic separation under gradient mobile solution con-
ditions (straight hexanes followed by 0.5% and usually up to 3%
ethyl acetate in hexanes) to provide a modest isolated yield of tri-
azene products (20e40%).
2. Conclusion
In conclusion, the addition of methanolic solutions of carbon-
ates or carboxylates to shelf stable isolated diazonium tetra-
fluoroborate salts dissolved in DMF has enabled the preparation of
a variety of triazene derivatives under mild and operationally
straightforward conditions. From a microscopic perspective, this
chemical transformation harnesses the potential energy of diazo-
nium salt starting materials by producing relatively more stable
aryl dialkyl triazene products [3b,54] under mild conditions.
Furthermore the accompaniment of the irreversible loss of gaseous
species facilitates the reaction progress. This modified methodol-
ogy for the generation of 1-aryl-3,3-dialkyl-triazenes has been
accomplished by way of in situ generated dimethyl amine radicals
(or related species) originating from DMF and their subsequent
coupling with isolated diazonium salts 1. Activation appears to
embark only once the dropwise addition of the carbonate/carbox-
ylate species to the diazonium salt commences [55]. In this regard,
visual reaction progress analysis demonstrates an immediate onset
2.3. Detailed experimental procedure
An actual procedure follows. A homogeneous methanolic solu-
tion is created by combining cesium carbonate (391 mg, 1.21 mmol,
1.6 equivalents) with phenyl propiolic acid (109 mg, 0.75 mmol, 1.0
equivalents) with complete dissolution occurring over a 1-h period.
(Here as well, many successful procedures used just a slight excess
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