Beilstein Journal of Organic Chemistry 2009, 5, No. 24.
potential TOP type catalyst based on the excellent work of migrate to the surface where the holes react with water (or
under various energy sources (Table 1).
strong oxidants [21]. Nevertheless, the activation of titanium
dioxide under microwave irradiation is surprising since UV
light is more intense than microwave energy. However, low
has been suggested [23] that microwave energy can couple with
a crystalline solid generating a non-thermal distribution,
resulting in an increase in ion mobility, which leads to the diffu-
sion of electrons and positive holes to the surface and
subsequent hydroxyl radical formation [24]. It is believed that a
similar interaction is taking place in our system and in conjunc-
tion with TEMPO lead to the formation of keto-aldehydes or
diketones, which are trapped in situ to produce the required
products.
Table 1: Evaluation of energy sources.
Entry
Energy source
Time (h)
Yield (%)a,b
i
Natural sunlight
Incandescent lamp
UV light
3
90
25
10
87c
ii
3
iii
iv
3
Microwave
10 min
aMixture of TiO2 (0.5 mmol), alcohol (0.5 mmol), amine (0.5 mmol) and
TEMPO (0.05 mmol) in 3 ml methanol. bIsolated yield. cAbsence of
solvent.
In an attempt to extend the methodology, a preliminary invest-
igation into a titanium dioxide mediated tandem Wittig reaction
Titanium dioxide is known to be highly reactive under sunlight was attempted in which the intermediate aldehyde is trapped by
17] and this seemed to be the most obvious starting point. a stabilised phosphorane. Unfortunately, NMR spectroscopic
Initially, 2-hydroxyacetophenone was reacted with o-phenyle- analysis revealed a multitude of peaks, none of which were
nediamine under natural sunlight. We were delighted to observe attributable to the product. It is believed that this is due to the
the formation of the quinoxaline derivative in an isolated yield non-selective nature of the hydroxyl radicals [25]. Currently
of 90% in 3 h. While encouraged by this result we immediately studies are under way to moderate the reactivity of the titanium
realized the limitations of this procedure. The use of an incan- dioxide. In a recent publication [26], Zhao and co-workers
descent lamp gave a disappointing yield of 25% while a low reported the use of dye-sensitized titanium dioxide and TEMPO
wattage UV light afforded an equally disappointing yield of for the selective oxidation of alcohols to aldehydes and ketones.
1
0% in 3 h. We explored the use of microwave energy, which In our studies we have been examining similar systems with a
has been claimed to substantially improve reaction rates [18]. view to incorporating them into tandem type processes.
Surprisingly, the use of microwave energy produced the best
result with the quinoxaline derivative isolated in a yield of 87% Conclusion
in 10 min. With the optimized procedure in hand, an investiga- In summary, we have reported the use of titanium dioxide as a
tion into the scope of the methodology, using a range of alco- tandem oxidation catalyst, demonstrated by the rapid synthesis
hols and diamines, was conducted (Table 2).
of quinoxalines under microwave irradiation. The process is
advantageous due to the green credentials and low cost of the
After the successful synthesis of quinoxaline 3a, the effect of an oxidant, short reaction times and good yields.
alkyl substituent was explored, which is often claimed to be
Experimental
problematic due to the ‘hyper-reactivity’ of the intermediate
keto-aldehyde [19]. The reaction afforded the quinoxaline 2-Phenylquinoxaline (3a)
derivative 3b in a satisfactory isolated yield of 60%. The coup- 2-Hydroxyacetophenone (0.068 g, 0.50 mmol), o-phenylene-
ling of secondary alcohols 1c and 1d both proceeded smoothly, diamine (0.054 g, 0.50 mmol), titanium dioxide (0.040 g, 0.50
even though the hindered alcohol 1c required a longer reaction mmol) and TEMPO (0.008 g, 0.050 mmol) were added to a
time. Finally, the diamine component was varied (entries v-vii) sealed 10 mL CEM Discover® reaction vial equipped with a
with satisfactory yields obtained for both primary and magnetic stirrer bar. The reaction vial was irradiated (at 150 W
secondary alcohols.
with cooling) for 10 min (2 × 5 min) at 150 °C, after which the
vessel was rapidly cooled to 50 °C by the unit. The reaction
Concerning the mechanism, when titanium dioxide is irradiated mixture was diluted with dichloromethane (DCM) and passed
with an appropriate energy source, electrons are promoted from through a short silica plug. The solvent was removed in vacuo
the valence band to the conduction band leaving behind positive to produce a crude product which was purified using radial
holes in the valence band [20]. The positive holes and electrons chromatography (3:1 PE:EtOAc) to afford the pure product.
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