Organic Letters
Letter
Brief experimentations demonstrated that low concentration
position, 2b[X] and 2f[X] for the C(1) position, and 2c[X] for
the analogous C(5) position. This is in full agreement with
DFT computational results. Also in each reaction, only a single
product, starting material, and intractable highly colored
byproducts were observed. In the case of 2f[Br], radical
1b[Br] was accompanied by its debromination product 1b.
(
∼1 mM) degassed solutions in CH Cl exposed to a 300 W
2
2
halogen lamp work well, and after 12 h of irradiation radical 1a
was isolated in 31% or 98% yield, considering recovered,
47
unconsumed starting 2a[NO ] (Figure 2). Similar experi-
2
ments with 2a[Br] gave 1a in higher yields (64%), while the
unsubstituted 2a[H] gave 1a in 40% yield after 72 h of
irradiation. Photocyclization reactions of 1-substituted 2-
naphthyloxy derivatives 2b[X] were more efficient. For
instance, radical 1b was isolated in 35% yield from 2b[Br]
The requisite precursors 2[H], 2[Br], and 2[NH ] were
2
31
obtained from 8-fluoro-3-phenylbenzo[e][1,2,4]triazine (3)
by nucleophilic aromatic substitution reactions with appro-
priate ortho-substituted phenols 4[X] in the presence of NaH
(Scheme 1). Reactions of 3 with 2-nitro-1-naphthol
after 3 h and in 55% from 2b[NO ] after 6 h (Figure 2). It was
2
observed that 2b[NO ] was so photoreactive that it was
(4d[NO ]) did not yield the substitution product even at
2
2
higher temperatures, presumably due to steric effects. There-
fore, 2e[NO ] was obtained in a similar manner using 8-
2
hydroxy-3-phenylbenzo[e][1,2,4]triazine (5) and nitro deriva-
tive 6e[NO2].
a
Scheme 1. Synthesis of Derivatives 2[X]
a
Reagents and conditions: (i) ortho-substituted phenol 4[X], 60%
NaH, DMSO, 80 °C, 1−12 h; (ii) ortho-halo nitroarene 6[NO ], 60%
2
+
−
NaH, DMSO, 80 °C, 1 h; (iii) [Bu N] OH , THF, 80 °C, 48 h.
4
Figure 2. Photocyclization of 2[X] to radicals 1: Method: 2[X] (300
mL CH Cl , c ≈ 1 mM) is irradiated with a 300 W halogen lamp at
For a better understanding of experimental results, photo-
cyclization of model derivatives 2[X], in which the C(3)−Ph
group is replaced with a hydrogen atom, was modeled at the
2
2
3
0−35 °C for 3−72 h in a Pyrex flask. Time, yields of isolated 1 and
yields based on consumed 2[X] are given.
(
TD)CAM-B3LYP/6-31G(d,p) level of theory using a relaxed
scan of the PES along the N(1)···C trajectory (e.g., Figure
).
Analysis of results indicates that the heights of the energy
Similar efficiency of cyclization was observed for 6-
48
3
quinolinoxy derivatives 2c[H] and 2c[NH ], for which 1c
2
was isolated in 14% and 47% yield, respectively, after 12 h of
exposure to halogen lamp light. The yield was essentially the
same in the presence of air. Irradiation of 1-naphthyloxy
derivative 2d[H] gave complete consumption of the staring
material in 48 h, and radical 1d was isolated in 85% yield.
Extending the irradiation time did not significantly affect the
yields presumably due to increased optical density of the
solutions and possible photodegradation of the radicals.
Similarly, high yields of 1e were obtained by irradiation of 3-
barrier to cyclization of 2[X] in the S state is lower for X =
1
NH and H than for X = NO . Results also demonstrate a
2
2
strong preference for regioselective cyclization at the C(1)
position of naphthalene in 2b[X] and 2f[X] (Figure 3) and for
the C(5) position in 6-quinolinoxy derivatives 2c[X].
Inspection of the lowest energy excitations of 2[X] shows
that the observed regiochemistry of cyclization corresponds to
the distribution of the excited state, and that the density of the
π orbital localized on the aryloxy fragment could be used as a
nitro-4-quinolinoxy derivative 2e[NO ] (Figure 2). In
48
2
contrast, no expected radical 2f was formed by irradiation of
3
2
-bromo or 3-amino-2-naphthyloxy derivatives, 2f[Br] and
f[NH ]. Instead, the former gave a mixture of 1b[Br] and 1b
2
in about 1:10 ratio, based on MS data, while the product of the
latter precursor was isolated in a low yield and identified as
1
b[NH ]. This selectivity for photocyclization at the
2
naphthalene C(1) position suggests a possible route to
functionalized derivatives. The desired radical 1f was obtained
in 14% yield by treatment of 2f[Br] with t-BuLi and in 76%
yield by thermolysis of N-nitrosoacetamide 2f[N(NO)Ac]
25,32
32
according to previous methods.
The aza-Pschorr method
did not yield radicals 1b and 1c using 2b[NHAc] and
2
c[NHAc], respectively.
Comparative analysis of photocyclization products revealed
Figure 3. Relative energy of a PES relaxed scan along the N(1)···C(1)
vector (blue), leading to 1b, and N(1)···C(3) vector (red), leading to
complete selectivity in cyclization of 2a[X] for the C(2)
1f, in the S state of model 2b[H]*.
1
B
Org. Lett. XXXX, XXX, XXX−XXX
Bartos, Paulina
