Unexpected imidazoquinoxalinone annulation products in the photoinitiated reaction of substituted-3-methyl-quinoxalin-2-ones with N-phenylglycine

Article abstract of DOI:10.1111/php.12162

Photoinduced electron transfer between N-phenylglycine (NPG) and electronically excited triplets of 7-substituted-3-methyl-quinoxalin-2-ones in acetonitrile generate the respective ion radical pair, where by decarboxylation the phenyl-amino-alkyl radical, PhNHCH₂?, is generated. This radical reacts with the 3-methyl-quinoxalin-2-ones ground states, leading to the product 2. Other, unexpected, 7-substituted-1,2,3,3a-tetrahydro-3a-methyl-2- phenylimidazo[1,5-a]quinoxalin-4(5H)-ones, annulation products, 3a-f, were generated; likely by the addition of two PhNHCH₂? radicals, to positions 3 and 4 of the quinoxalin-2-ones. The reaction mechanism includes a photoinduced one electron transfer initiation step, propagation steps involving radical intermediates and NPG with radical chain termination steps that lead to the respective products 2a-f and 3a-f and NPG by-products. The proposed mechanism accounts for the strong dependency found for the initial photoconsumption quantum yields on the electron-withdrawing power of the substituent. Therefore, photolysis of common reactants widely used such as NPG and substituted quinoxalin-2-ones may provide a simple synthetic way to the unusual, unreported tetrahydro-imidazoquinoxalinones 3a-f.

Full text of DOI:10.1111/php.12162

Photochemistry and Photobiology, 2013, 89: 1335–1345
Unexpected Imidazoquinoxalinone Annulation Products in the
Photoinitiated Reaction of Substituted-3-Methyl-Quinoxalin-2-Ones
with N-Phenylglycine†
1
2
1
1
3
ꢀ
~
Julio R. De la Fuente *, Alvaro Canete , Carolina Jullian , Claudio Saitz and Christian Aliaga
1
ꢀ
ꢀ
Departamento de Química Organica y Fisicoquímica, Facultad de Ciencias Químicas y Farmaceuticas, Universidad de
Chile, Santiago, Chile
2
ꢀ
ꢀ
Departamento de Química Organica, Facultad de Química, Pontificia Universidad Catolica de Chile, Santiago, Chile
3Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago,
Chile
Received 15 May 2013, accepted 19 August 2013, DOI: 10.1111/php.12162
strongly suggest that the quinoxalin-2-one derivatives might
interact with potential electron-donating amino acids residues.
ABSTRACT
Photoinduced electron transfer between N-phenylglycine
Despite the thoughtful biological, synthetic and pharmacologi-
(NPG) and electronically excited triplets of 7-substituted-3-
methyl-quinoxalin-2-ones in acetonitrile generate the respective
ion radical pair, where by decarboxylation the phenyl-amino-
alkyl radical, PhNHCH2•, is generated. This radical reacts
with the 3-methyl-quinoxalin-2-ones ground states, leading
to the product 2. Other, unexpected, 7-substituted-1,2,3,3a-
tetrahydro-3a-methyl-2-phenylimidazo[1,5-a]quinoxalin-4(5H)-
ones, annulation products, 3a–f, were generated; likely by the
addition of two PhNHCH2• radicals, to positions 3 and 4 of
the quinoxalin-2-ones. The reaction mechanism includes a
photoinduced one electron transfer initiation step, propaga-
tion steps involving radical intermediates and NPG with radi-
cal chain termination steps that lead to the respective
products 2a–f and 3a–f and NPG by-products. The proposed
mechanism accounts for the strong dependency found for the
initial photoconsumption quantum yields on the electron-
withdrawing power of the substituent. Therefore, photolysis
of common reactants widely used such as NPG and substi-
tuted quinoxalin-2-ones may provide a simple synthetic way
to the unusual, unreported tetrahydro-imidazoquinoxalinones
3a–f.
cal studies on quinoxalin-2-one derivatives there are relatively
few reports on the photochemical and the radical chemistry of
these heterocyclic compounds. Some derivatives initiate free rad-
ical polymerization by electron transfer from N-phenylglycine
(NPG) used as an electron donor (13). Photoreduction of quinox-
alin-2-ones by amines originates the corresponding dihydro-
quinoxalin-2-ones or the reductive dimers, depending on the
substituent in position 3 of the heterocycle ring (14). Also,
efficient [2 + 2] cycloadditions of quinoxalin-2-ones and related
oxazinones with alkenes leading to tricyclic azetidines have been
reported (14–18).
Ten years ago we studied two 3-phenyl-quinoxalin-2-one
derivatives and found a nearly quantitative reversible photoreduc-
tion by amines (19). This photoreduction proceeded through a
stepwise transference of electron–proton–electron from the amine
to the excited triplet of the 3-phenyl-quinoxalin-2-ones, leading
to a metastable semireduced anion capable of reverting almost
quantitatively to the original quinoxalin-2-ones.
This photoreduction mechanism was further supported by
laser flash photolysis experiments which allowed the identifica-
tion of the photoreduction intermediate absorptions (20). The
stepwise electron–proton–electron transfer mechanism observed
for quinoxalin-2-one derivatives is similar to the one we reported
for the oxoisoaporphines derivatives studied in the last years
(21–25). Both kinds of compounds, quinoxalin-2-ones and oxo-
isoaporphines, contain conjugated C=N and C=O moieties in
their structures, which are the groups inducing their photoreactiv-
ity toward amines, showing the unusual thermal reversion of
metastable semireduced photoproducts.
INTRODUCTION
In the last few decades, many studies on the biological properties
of quinoxalin-2-one derivatives have been published because of
their several pharmacological properties such as: antimicrobial,
antifungal, anxiolytic, analgesic, antithrombotic, antitumoral and
due to their capacity as inhibitors of the activity of certain
enzymes involved in HIV-1 (1–8).
Several works locate the quinoxalin-2-one derivatives inside
different proteins receptors, generally close to the ATP-binding
pocket. These interactions have been modeled by molecular
dynamics docking and in some cases the adduct structures were
supported by X-Ray crystallographic studies (9–12). These facts
In this article, we report the result obtained in the photoreduc-
tion in acetonitrile by NPG of six 7-substituted-3-methyl-quinox-
alin-2(1H)-one derivatives, 1a–f, shown in Chart 1.
We selected NPG as a model reductant amino acid because its
radical cation, NPG•+, likely present as the carboxylate zwitterion
radical PhN(H)•+-CH2COOꢀ has a reported absorption at 460 nm
(26), which will be helpful for future laser flash photolysis studies.
Together with this absorption, NPG•+ decarboxylates rapidly (27)
at rates >108 sꢀ1, generating the phenyl-amino-alkyl radical
*Corresponding author email: jrfuente@ciq.uchile.cl (Julio R. De la Fuente)
†This article is part of the Special Issue dedicated to the memory of Elsa Abuin
© 2013 The American Society of Photobiology
1335

1336 Julio R. De la Fuente et al.
1f: 7-Cyano-3-methyl-1H-quinoxalin-2-one—HRMS (EI+) m/z cal-
culated for C10H7N3O: 185.05891; found: 185.05877. 1H NMR
(300 MHz, CDCl3) d 11.88 (s, 1H, NH), 7.91 (d, J = 8.3 Hz, 1H), 7.64
(d, J = 1.3 Hz, 1H), 7.59 (dd, J = 8.3, 1.6 Hz, 1H), 2.68 (s, 3H).
HRMS (70 eV) [EI+]: for product 3a: m/z calculated for C18H19N3O2:
309.14773; found 309.14766 and for product 3e; m/z calculated for
C18H16F3N3O, 347.12455: found 347.12462. Poor quality 13C NMR
spectra were obtained due to the low amount of isolated products.
Steady-state photolysis. Typically acetonitrile solutions (3 mL) con-
taining 0.1 mM of substrates 1a–f, with absorbances approximately 1.0 at
366 nm, in the presence of appropriate NPG concentration were saturated
with Ar for 20 min, protected from light. Each sample was photolyzed
directly in the spectrophotometer with a 150 W low-pressure Hg lamp,
equipped with a 366 nm filter in an Agilent 8453 diode array spectropho-
tometer provided with a stirred cell holder. For the perylene photosensi-
tized reaction, a filter absorbing below 385 nm was used and the
photolysis time was limited to 20 min. Stock solutions of each reactant
were prepared and mixed in the appropriate proportions before Ar bub-
bling. During these procedures, the samples were protected from light.
Typical concentration in the quartz cell was 0.05 mM perylene, approxi-
mately 1 mM NPG and between 0.05 and 0.8 mM, for 1d–f. The initial
concentrations of perylene and NPG were kept constants in these
experiments. The photolyzed samples at the higher [1d-f] were also ana-
lyzed by GC–MS. For these experiments, the photoconsumption was
evaluated as the absorbance difference at t = 0 and t = 20 min:
Abst=0 ꢀ Abst=20 min, at each considered wavelength.
H
R
R
N
O
a = CH3O
b = CH3
c = F
N
d = H
e = CF3
f = CN
1
Chart 1. Structure
of
7-substituted-3-methyl-quinoxalin-2(1H)-one
derivatives.
PhNHCH2• absorbing at 400 nm (28). The fast decarboxylation of
NPG•+, Scheme 1, should avoid a back electron transfer to the
electron acceptor.
MATERIALS AND METHODS
Materials. Acetonitrile Merck, HPLC grade and acetonitrile-d3 99% D,
Aldrich, spectroscopic grade were used as received. NPG, Aldrich 97%,
was crystallized twice from water before use.
Synthesis of substituted 3-methyl-2(1H)-quinoxalin-2-ones 1a–f.
Substituted 3-methyl-2(1H)-quinoxalin-2-ones 1a–f were prepared by the
classical reaction of the corresponding o-phenylendiamines (1 mmol) by
adding drop by drop methyl pyruvate (1.2 mmol) and triethylamine
(3 mmol) in ethanol (5,15). Solutions were heated at 80°C for 2 h under
nitrogen atmosphere. After 2 h the heating was stopped and the reactants
were allowed to cool. The contents of the flask were filtered through celite
under reduced pressure and washed with a minimal amount of absolute eth-
anol. The solvent was removed in vacuum to afford the crude compound,
which was purified by flash column chromatography eluted with ethyl ace-
tate:hexane 9:1 and finally crystallized from acetonitrile, to give the pure
quinoxalin-2-one derivatives. In reactions where a mixture of isomers in
positions 6 and 7 was obtained, the isomers were separated by flash column
chromatography using silica gel and THF:1,2-dichloroetane 1:1.
The spectral characterization of 1a–f by 1H NMR and HRMS (EI+) is
in agreement with the expected structures. DMSO-d6 1H and 13C NMR
for the substrates are provided as Supplementary Materials.
Preparative photolysis. Preparative photolysis was done in acetonitrile
for derivatives 1a and e with solutions containing 150 mg of NPG and
approximately 40 mg (1.8–2.1 mmol) of 1e and
a respectively, in
150 mL acetonitrile HPLC quality, and bubbled with Ar for 1 h. Photol-
ysis of these solutions, under continuous Ar bubbling and stirring, using
a 150 W Black Ray UV lamp equipped with a 366 nm filter, was per-
formed for 2 h. Samples of the products (0.5 mL) were reserved for GC-
mass analyses. The remnant was dried out, and seeded in Merck, Silica
gel 60F254 2 mm thin layer preparative plates, which were eluted with
hexane:ethyl acetate 1:1, which showed seven main separated bands.
These bands were scraped and extracted in acetonitrile, to prepare sam-
ples for GC mass. The fraction of interest was further purified by thin
layer chromatography (TLC) with hexane:ethylacetate; 3:1, dried out and
dissolved in deuterated acetonitrile for NMR spectroscopy.
NMR spectroscopy. 1H NMR, COSY, HMBC, HMQC and 13C NMR
DEPT 135º were done in a Bruker Advance DRX-400, 400 MHz spec-
trometer, using tetramethylsilane as the internal standard. Due to the low
concentration of the samples, experiments lasted several hours.
1a: 7-Methoxy-3-methyl-1H-quinoxalin-2-one—HRMS (EI+) m/z
calculated for C10H10N2O2: 190.07422; found: 190.07420. 1H NMR
(300 MHz, CDCl3) d 11.49 (s, 1H, NH), 7.70 (d, J = 8.9 Hz, 1H), 6.92
(dd, J = 8.9, 2.6 Hz, 1H), 6.71 (d, J = 2.6 Hz, 1H), 3.91 (s, 3H), 2.58
(s, 3H).
Photoconsumption quantum yields (ΦPC). Photoconsumption quantum
yields (ΦPC) were evaluated from the initial photoconsumption rates, V0,
measured at the maximum of the lower energy absorption band of the
respective substrates 1a–f and corrected by the initial sample absorption
at 366 nm, A-366, against Aberchromeâ540 (29), taking ΦAber = 0.2
1b: 3,7-Dimethyl-1H-quinoxalin-2-one—HRMS (EI+) m/z calculated
for C10H10N2O: 174.07932; found: 174.07911. 1H NMR (300 MHz,
CDCl3) d 12.45 (s, 1H, NH), 7.67 (d, J = 8.6 Hz, 1H), 7.6 (s, 1H), 7.13
(dd, J = 7.6 Hz, 1H), 2.62 (s, 3H), 2.48 (s, 3H).
ꢀ1
and; eAber at 494 nm as 8200 M cmꢀ1. The expression used was as fol-
1c: 7-Fluoro-3-methyl-1H-quinoxalin-2-one—HRMS (EI+) m/z cal-
culated for C9H7FN2O: 178.05424; found: 178.05412. 1H NMR
(300 MHz, CDCl3) d 11.92 (s, 1H, NH), 7.79 (dd, J = 8.8, 5.6 Hz, 1H),
7.06 (dd, J = 5.5, 2.8 Hz, 1H), 7.03 (t, J = 2.7 Hz, 1H), 2.61 (s, 3H).
1d: 3-Methyl-1H-quinoxalin-2-one—HRMS (EI+) m/z calculated for
C9H8N2O: 160.06366; found: 160.06344. 1H NMR (300 MHz, CDCl3) d
11.38 (s, 1H, NH), 7.81 (d, J = 8.1 Hz, 1H), 7.49 (t, J = 7.1 Hz, 1H),
7.29-7.33 (m, 2H), 2.64 (s, 3H).
lows: ΦPC = (V0/ekmax 9 ΦAber)/[VAber/eAber 9 (1 ꢀ 10Aꢀ366)], where
ekmax was the absorption coefficient of 1a–f at the wavelength maximum
and VAber the rate of the appearance of absorption at 494 nm. All these
experiments were made with 3 mL solutions in acetonitrile at absor-
bances between 0.9 and 1.1 for [1a–f] approximately 0.1 mM and with
[NPG] > 1 mM, in the plateau zone.
GC–MS spectral analyses and HRMS were obtained using a MAT 95 XP
Thermo Finnigan Spectrometer at 70 eV EI+. High-resolution mass spectra
were made at 70 eV (Positive) with reference perfluoro kerosene. Low-pres-
sure CI analyses, using methanol as reagent, were done in a Varian 421-GC
with a 220-MS detector. Mass–mass tandem spectra were obtained in a
Thermo Scientific Quantum XLS triple quadrupole detector, in a Trace GC,
1e: 3-Methyl-7-trifluoromethyl-1H-quinoxalin-2-one—HRMS (EI+)
m/z calculated for C10H7F3N2O: 228.05106; found: 228.05110. 1H NMR
(300 MHz, CDCl3) d 10.31 (s, 1H, NH), 7.92 (d, J = 8.4 Hz, 1H), 7.56
(d, J = 8.4 Hz, 1H), 7.47 (s, 1H), 2.65 (s, 3H).
H
H
H
H
H
O
H
O
H
O
H
H
O
H
N
N
- e-
+ H+ + CO2
N
H
Scheme 1. Decarboxylation of N-phenylglycine radical cation.

Photochemistry and Photobiology, 2013, 89 1337
with a column Restek Rtx-5MS 30 m 9 0.25 mm 9 0.25 lm GC–MS/MS.
Oven method: Initial temperature 70°C, initial time 2.0 min, ramp 1°C/min,
final temperature 300°C, hold time 4.0 min and constant flow of 1 mL/min;
carrier gas He.
7.0x10-7
0.4
0.2
6.0x10-7
5.0x10-7
4.0x10-7
3.0x10-7
2.0x10-7
CN
CF3
Laser flash photolysis experiments were performed on the modernized
instrument described previously (20,23,25). Now it was provided with a
Continuum Surelite I 10 Hz Q-switched Nd-YAG laser and the signals
were now captured by a WaveSurfer 600 MHz LeCroy oscilloscope.
Software written in National Instrument LabViews 8.0 controls the laser,
monochromator and shutters and captured the data which are fed to Igor
Pro 6.3 written program for treatment and display. The system is pro-
vided with a peristaltic pump and a 0.5 mL flow cell to assure the con-
tinuous renovation of solutions. Optimal results were obtained with
solutions with absorbances between 0.4 and 0.6 at the 355 nm excitation
wavelength. The laser power impinging the cell was attenuated using
glass plates to ~10 mJ per pulse. Quenching experiments were typically
made with solutions (3 mL) of substrates bubbled with Ar for 20 min in
10 mm square quartz cells sealed with a septum. After purging, aliquots
of quenchers were added and the lifetimes s at definite wavelengths mea-
sured. Quenching constants were obtained from slopes of Stern–Volmer-
type plots of 1/s vs [quencher] which resulted in linear regression with
r > 0.95 in all of the experiments.
1.0x10-7
0.0
F
0.0
H
0
1
2
4
[NPG] mM 3
-0.2
-0.4
-0.6
-0.8
CH3
ρ
= 0.577 +/- 0.04
r = 0.97077
CH3O
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
σ+
0.2
0.4
0.6
0.8
Figure 2. Hammett plot for the Φpc/Φpc-H vs the electrophilic substituent
parameter r+ often used for radical reactions. The inset shows the [N-
phenylglycine] effect in the initial photoconsumption rate, V0, for 0.1 mM
7-F-derivative 1c, V0 expressed Abs/s.
Transient spectra in the presence of 1,4-diazabicyclo[2.2.2]octane
(DABCO) or NPG were obtained with Ar bubbled 250 mL acetonitrile
solutions containing 0.1 mM of the quinoxalin-2-one. These solutions
were monitored in the 0.5 mL flow cell at a flow rate of 1 mL/min tak-
ing a mean of five laser shots for each monitored wavelengths at each
DABCO or NPG concentration used. The Ar bubbling was maintained
during the whole experiment.
Table 1. Photoconsumption quantum yields for the photoreduction of 7-
substituted-3-methyl-quinoxalin-2-ones by N-phenylglycine with the
respective electrophilic substituent Hammett parameter r+.
RESULTS AND DISCUSSION
Derivative
Substituent 1a CH3O 1b CH3
1c F
1d H 1e CF3 1f CN
Steady-state photolysis
+
r
ꢀ0.778
ꢀ0.311 ꢀ0.073
0.68 1.15
0.0
1.10
0.612
1.88
0.659
2.49
ΦPC
*
0.27
All of the quinoxalin-2-one derivatives studied were photostable
in air-saturated acetonitrile solutions, irrespective of the presence
of NPG. In argon-saturated solutions, a fast photoreaction with
significant spectral changes occurred. One or several isosbestic
points appeared, depending on the quinoxalin-2-one substituent.
These isosbestic points strongly suggest the formation of a single
product or a mixture in a constant molar ratio. The absence of
photoreaction in air-saturated solutions strongly points to a reac-
*Photoconsumption quantum yields are the average of two or more mea-
sures and have a bounded 5% error.
tion from the quinoxalin-2-ones triplet manifold. As an example
of these photoreactions, Fig. 1 is included, showing the 7-CF3-
derivative 1e photoreduction by NPG with three isosbestic points
in the spectral region of interest.
For all of the derivatives studied, the initial photoconsumption
rates were strongly dependent on the NPG concentration, increas-
ing monotonically up to plateau values at [NPG] ≥ 1.5 mM, for
~0.1 mM quinoxalin-2-ones, (for the 7-fluor derivative, 1c, see
inset in Fig. 2). By measuring initial rates, at [NPG] in the plateau
region, photoconsumption quantum yields, Φpc, were evaluated as
described in the Experimental Section. The values determined for
Φpc were as low as 0.27 for the 7-CH3O derivative, 1a, to a
surprisingly high 2.49 for the 7-CN derivative, 1f. This large Φpc
value cannot be explained by considering only a photochemical
reaction between electronically excited 1 and NPG, suggesting a
radical chain reaction between photochemically NPG-generated
radicals and likely, the ground state quinoxalin-2-one.
Interestingly, the Φpc increased with an increase in the
electron-withdrawing power of the substituent (Table 1) and
correlated well with the Hammett electrophilic substituent r+
parameter (30), with a q = 0.577 ꢁ 0.04 (r = 0.9708), as shown
in Fig. 2. The observed correlation strongly suggests that the
reaction mechanism is the same for all the derivatives studied,
irrespective of the quinoxalin-2-one substituent.
2.0
1.5
1.0
0.5
0.0
8.0x10-5
6.0x10-5
4.0x10-5
335 nm
351 nm
[1e] / M
2.0x10-5
0.0
0
500
1000 1500 2000 2500 3000
t / s
250
275
300
325
350
375
400
λ
nm
Figure 1. Photolysis of 0.1 mM CF3-substituted derivative 1e in the
presence of 1.0 mM N-phenylglycine. The arrows show the absorbance
changes. The inset shows the kinetic traces at 335 nm (□) and 351 nm
(○) used to evaluate the initial rates for photoconsumption quantum
yields.
Positive q values, similar to those obtained in this work, have
been related to radical addition reactions of alkyl radicals to the
aromatic nuclei of substituted toluenes (31), to aminoxyl radical
addition to arylketenes (32), to the ratio between addition and

1338 Julio R. De la Fuente et al.
electron abstraction on aromatic rings (33–35) and to the addi-
tion of thiyl radicals to vinyl monomers (36,37).
Product GC-MS analysis
Electronic impact, EI GC-mass analysis of the photolyzed sam-
ples, reveals several NPG oxidation products such as: aniline
Taking into account the stepwise photoreduction reported for 3-
phenyl-quinoxalin-2-ones (19,20), the lack of any photoreaction
for 1a–f derivatives in aerated samples, and some laser flash pho-
tolysis results (vide infra) that showed that the first step of photore-
action is mainly a one electron transfer from the NPG, as
PhNHCH2COOꢀ, to the excited triplet state of the substituted
3-methyl-quinoxalin-2-one, 31, it can be proposed that the
formation of a ion radical pair, Eq. (1) is the first step of the photo-
reaction.
(PhNH2,
m/z = 93)
and
N,N′-diphenylethylenediamine
((PhNHCH2)2, m/z = 212), which are confirmed by comparison
with the respective standards, and N-methylenebenzenamine
(PhN=CH2, m/z = 105), which was identified by its database
NIST© mass spectra. In addition, NPG excess with m/z = 151
and the remnant quinoxalin-2-ones with their respective m/
z = M, for each derivative 1a–f were also detected.
3
H
N
H
*
−
•
R
O
R
N
O
+ PhNHCH2COO-
NPG
+ PhNHCH2COO-
NPG•+
N
N
(1)
−
31*
1•
Reaction of 1●ꢀ with media H+ from the NPG should lead to
the captodative-stabilized radical (H)1• and by decarboxylation
of NPG•+ should be formed the radical PhNHCH2•, Eq. (2). The
quinoxalin-2-one radical anion 1•ꢀ is similar to those reported
previously as intermediaries by us for the amine photoreduction
of 3-phenyl-quinoxalin-2-ones (19,20).
The presence of N-methylenebenzenamine and N,N′-dipheny-
lethylenediamine in the product mixtures strongly supports
the involvement of PhNHCH2• in the photoreaction and hence
the decarboxylation reaction of Scheme 1. Among the mentioned
NPG products, other unidentified NPG products with m/z: 223,
H
H
H+
R
N
O
.
N
H
–
1 + NPG
+
+ CO2
(2)
H
N
H
.
(H)1
On the other hand, by considering a competitive hydrogen
transfer from the NPG to the excited quinoxalin-2-one, a fast for-
mation of (H)1• and the a-aminoalkyl radical PhNH-•CHCOOꢀ
which after protonation also decarboxylate (27,28), leading to the
same radicals shown in Eq. (2) can be expected. Flash photolysis
experiments (vide infra) show evidence of this competitive con-
tributing reaction path.
The combination of the two radicals PhNHCH2• and (H)1•
should lead to product 2, Eq. (3), with a nominal mass M + 107,
where M is the molecular mass of the original 7-substituted-3-
methyl-quinoxalin-2-one.
230 and 340 appeared in all of the experiments, independent of
the quinoxalin-2-one substituent.
For all of these experiments, the EI GC-mass analysis showed
only two quinoxalin-2-one main products for each of the 1a–f
products investigated. These products can be easily recognized
because their m/z ratios differ in the substituent masses. The first
product, appearing at lower retention times, had a m/z = M + 2,
and the second, totally unexpected products, named 3, appearing at
longer retention times, had a m/z = M + 119, where M is the nom-
inal mass of the respective 7-substituted-quinoxalin-2-one deriva-
tives 1a–f.
H
H
R
N
O
N
H
.
(H)1 +
(3)
H
N
H
HN
2

Photochemistry and Photobiology, 2013, 89 1339
In these analyses, the expected product 2, from the radical
addition, Eq. (3), with m/z = M + 107 was not found. The detec-
tion of a product with m/z = M + 2 suggests the formation of
the dihydro-quinoxalin-2-one derivatives by the reduction in the
imino moiety. To confirm the m/z ratio for these products, a
more mild chemical ionization detection (CI GC–MS) was used
for the analyses of photolyzed mixtures for substrates 1a and e.
We selected these derivatives because their substituents have
similar but opposed r+ values. The results of these analyses
show products 2a and e appearing with m/z = M + 108, with M
being the mass of 1a or e. These findings agree with the addition
of PhNHCH2• plus the extra proton added by the CI. Therefore,
by extension, the expected products 2a–f, are actually formed
with m/z = M + 107 molecular ion, which cannot be detected by
EI. Under the same conditions, that is CI GC–MS, the second
quinoxalin-2-one products 3a and e, appeared with m/
z = M + 120, confirming that the molecular ion m/z corre-
sponded to those obtained by EI mass analyses. Again M is
the mass of products 1a–f. These results are summarized in
Table 2.
These results clearly show that the expected addition products
2a–f are present after the photolysis and that the molecular ion
of product 3 has m/z = M + 119, suggesting the involvement of
at least two PhNHCH2• in their formation. Moreover, for both
products 2 and 3, the m/z ratios are odd for all the substituents
with the exception of CN. Therefore, according to the nitrogen
rule, these molecular ion masses confirm an odd number of N
atoms in both kinds of products, with the exception of the CN-
substituted product 3f.
336.00
H
F3C
N
O
100
80
60
40
20
0
+ H+
N
H
HN
336.90
316.00
2e
106.00
243.00
317.00
338.00
298.00
H
100
80
60
40
20
0
O
N
O
+ H+
N
H
HN
298.90
280.00
2a
205.00
223.00
151.80
281.00
300.00
193.00
106.00
100
150
200
250
300
350
m/z
Figure 3. Mass spectra for the molecular ions obtained by chemical ion-
ization for: the CF3-derivative product 2e and for the CH3O-derivative
product 2a. For the molecular ions, the m/z ratio corresponds to M + 1,
M being the molecular mass of products 2a–e.
Mass spectra analysis
Mass spectra of products 2a–f obtained by CI show similar fea-
tures for the substrates studied, with the release of two main neu-
tral fragments; one with nominal mass 93, which is independent
of quinoxalin-2-one substituent, and another dependent on it,
with mass M + 2, where M is the quinoxalin-2-one mass. This
fragment can explain the m/z ratio observed when using elec-
tronic impact ionization. The loss of 93 mass units, likely ani-
line, accounts for the observed peaks at m/z = 205 and 243,
shown in Fig. 3, for the products 2a and e, respectively. The
peak at m/z = 106, likely Ph+NH=CH2, accounts for the loss of
the M + 2 neutral fragments. These ionized fragments probably
are those observed in EI mass spectra. The fragmentation pattern,
the same for all of the substrates studied, fits well the proposed
structure for products 2a–f.
90.99
H
N
F3C
242.10
O
100
80
60
40
20
0
119.00
N
N
3e
213.47
198.85
347.15
91.99
90.99
132.86
171.94
245.16
204.11
H
O
N
O
100
80
60
40
20
0
In the same manner as for the products 2a–f, a regular frag-
mentation pattern was found for the products 3a–f, in the EI
GC-mass experiments. For all the photolyzed substrates, together
with the molecular ion with m/z = M + 119, the mass spectra
N
119.01
N
3a
308.19
Table 2. Nominal m/z ratio for the products molecular ions generated in
the photoreduction by N-phenylglycine of 7-substituted-3-methyl-quinox-
alin-2-ones 1a–f.
176.07
161.03
132.92
91.98
90.44
265.97
Derivative
Substituent
100
150
200
250
300
350
1a CH3O 1b CH3 1c F 1d H 1e CF3 1f CN
m/z
Substituent mass
m/z product 2
m/z product 3
31
297
309
15
281
293
19
285
297
1
267
279
69
335
347
26
292
304
Figure 4. Mass–mass spectra for product 3 molecular ions show the
common fragments with m/z = 91 and 119 and those corresponding to
M + 14 fragments; for the CF3-derivative 3e, m/z = 242; and B) for the
CH3O-derivative 3a, m/z = 204.

1340 Julio R. De la Fuente et al.
show two fragments with m/z 91 and 119 irrespective of the sub-
strate 1a–f. Others fragments derived from the loss of 105 mass
units with respect to the molecular ions, with m/z = M + 14
were found for all the derivatives. In Fig. 4 are shown the tan-
dem mass–mass spectra corresponding to the molecular ions 3a
and e, showing clearly the common 91 and 119 fragments, and
those with m/z 204 and 242 observed for 3a and e, respectively.
According to the nitrogen rule, these last fragments have an even
number of N atoms in their structure. Thus, these fragments with
shown in Eq. (4). This aniline elimination may occur by proton-
ation of one of the PhNHCH2 tethered to the quinoxalin-2-one
followed by the nucleophilic displacement of aniline. However,
this reaction requires two PhNHCH2• radicals, which have to be
generated in a radical chain reaction to explain the photocon-
sumption quantum yields observed for the most electron-with-
drawing substituted derivatives 1e and f, see Table 1 and Fig. 2.
To generate the two PhNHCH2• radicals needed to obtain
product 3, two electron or hydrogen transfers steps from NPG to
H
H
R
N
O
R
N
O
H
N
R
O
(
N
N
+ PhNH2
(4
+ 2PhNHCH2
HN
N
N
HN
3
m/z = M + 14 suggest a CH2 bounded to the original quinoxa-
lin-2-ones 1a–f and one N atom less than products 3a–f.
1, Eq. (1), followed by decarboxylation of the NPG radical
cations or their a-aminoalkyl radical are required. Hence, the
limit for the quinoxalin-2-one photoconsumption quantum yield,
Φpc, leading only to product 3 cannot be larger than 0.5. On the
other hand, by assuming that the reaction leads only to product
2, a Φpc = 1 can be expected. Any combination of both products
2 and 3 should give Φpc values below 1.0 but, for 1c–f, values
are larger than 1.0 and for 1e and f the observed values are 1.88
and 2.49, respectively. Therefore, a purely photochemical reac-
tion cannot explain the experimental results, suggesting a chain
radical propagation, leading to PhNHCH2• radicals. If this
assumption is true, generating the PhNHCH2• radicals in the pres-
ence of the quinoxalin-2-ones, but without involving any of their
excited states, the same photoproducts 2 and 3 should be found.
Product isolation and NMR analysis
The preceding mass spectra results do not give enough informa-
tion to elucidate the structure of the products. Therefore, we did
some preparative photolysis with 1a and e, and the products
were separated using TLC. The details are given in the Experi-
mental Section. Each fraction was extracted and analyzed by GC
mass searching for products 2 and 3. In these fractions, the same
above-mentioned NPG oxidation products were found. One of
these fractions contained nearly pure product 3. But product 2
was not found in any of the fractions, likely due to its decompo-
sition by a reaction with the TLC silica.
The fraction containing 3a or e was further purified by TLC,
Sensitized photolysis
1
dried out and dissolved in CD3CN for H NMR, COSY, HMBC,
HMQC and 13C NMR DEPT 135° experiments, which were
employed to elucidate their structure. The NMR results are sum-
marized in Table 3 and the 1H NMR spectrum for 3e is shown
in Fig. 5.
It was reported that the photolysis of NPG sensitized by polycy-
clic aromatic hydrocarbons, among the perylene, leads to the
PhNHCH2• radicals by electro-proton transfer (38). Perylene
which absorbs at longer wavelengths to not excite simultaneously
some of the substrates, 1d–f, seems a good sensitizer. Thus,
using the proper cut-off filter that transmits for k > 385 nm, we
can selectively excite perylene in the presence of substrates 1d–f
and NPG. In these experiments, the perylene and NPG concen-
tration were kept constant, while changing the substrate 1d–f
concentrations. The use of perylene as a photosensitizer pre-
cluded energy transfer to the quinoxalin-2-ones, thus any reaction
which can be observed should be attributed to the PhNHCH2•
radicals formed by proton transfer from NPG to excited perylene
(38,39). Details about this photosensitized reaction are given in
the Experimental Section. As we expected in the GC-mass analy-
ses of these samples, we found the respective products 2d–f and
3d–f, confirming the radical character of the reaction. Moreover,
by increasing the quinoxalin-2-one concentration at constant
[perylene] and [NPG], an increase in the consumption of NPG
and 1d–f, was observed, and concomitantly perylene consump-
tion decreased, as shown in Fig. 6 for 1d. These results show
that consumption increased by a factor of ~3 and 5 for 1d and
NPG, respectively, for a 7.5-fold increase in product 1d, at the
same photon flux. Similar results were obtained with the other
By extending these results to the other derivatives, which
show the same EI mass spectral pattern, products 3a–f can be
unequivocally identified as the respective 7-substituted-1,2,3,3a-
tetrahydro-3a-methyl-2-phenylimidazo[1,5-a]quinoxalin-4(5H)-
ones. Moreover, high-resolution mass spectra, HRMS, were
determined for 3a and f, with expected masses 309.14773 and
347.12455 and molecular ions were found with m/z 309.14766
and 347.12462, respectively. These values differ from the calcu-
lated exact mass by less than 0.25 ppm, confirming the proposed
structures. By considering these structures it is possible to
account for the fragments observed in mass spectra as shown in
Scheme 2.
To rule out other possible sources of product 3, we tested the
photoreactions of 1a and e with N,N′-diphenylethylenediamine
(PhNHCH2)2 and aniline, which appeared as NPG oxidation
products. All of these attempts were unsuccessful rejecting any
reaction with these NPG products.
The present results provide strong evidence that product 3 for-
mation should involve the attack of two PhNHCH2• radicals
derived from the NPG, followed by the elimination of aniline, as

Photochemistry and Photobiology, 2013, 89 1341
Table 3. 1H and 13C chemical shifts d [H-X, multiplicity, J(H,H) (Hz)]* of 3a-Methyl-2-phenyl-7-trifluoromethyl-1,2,3,3a-tetrahydro-5H-imidazo[1,5-a]
quinoxalin-4-one, 3e, and 7-methoxy-3a-methyl-2-phenyl-1,2,3,3a-tetrahydro-5H-imidazo[1,5-a]quinoxalin-4-one, 3a.
3e
3a
Position
1c
d(1H)
d(13C)
62.9¶
53.9¶
HMBC†
3, 3a
d(1H)
d(13C)
63.3¶
54.2¶
HMBC†
3, 3a
4.75 [H-1, d, J(1, 1) = 4.0]‡
4.97 [H-1, d, J(1, 1) = 4.0]‡
3.71 [H-3, d, J(3, 3) = 8.7]‡
3.77 [H-3, d, J(3, 3) = 8.7]‡
4.71 [H-1, d, J(1, 1) = 3.0]‡
4.83 [H-1, d, J(1, 1) = 3.0]‡
3.64 [H-3, d, J(3, 3) = 8.5]‡
3.76 [H-3, d, J(3, 3) = 8.5]‡
3c
CH3, 3a, 4
CH3, 3a, 4
3a
4(C=O)
5
—
—
62.1
167.0
—
—
—
—
—
—
62.0
167.0
—
—
—
—
8.74 [N-H, s]§
8.3 [N-H, s]
5a
6
7
8
9
9a
1′
2′
3′
4′
—
126.6
111.8
133.7
121.2
112.4
126.7
146.1
112.3
129.0
117.5
18.3
—
5a, 7, 8
—
—
120.6
99.7
—
5a, 7, 8
—
7.16 [H-6, s]
—
7.35 [H-8, d, J(8, 9) = 8.3]
6.81 [H-9, d, J(9, 8) = 8.3]
—
6.34 [H-6, s]
—
6.42 [H-8, d, J(8, 9) = 8.6]
6.83 [H-9, d, J(9, 8) = 8.6]
—
156.7
103.3
116.3
120.9
146.0
111.7
129.1
116.8
16.9
6, 7, 9, 9a
5a, 7, 8, 9a
—
6, 7, 9, 9a
5a, 7, 8, 9a
—
—
—
—
—
6.74 [H-2′, d, J(2′, 3′) = 7.9]
1′, 3′, 4′
1′, 2′, 4′
2′, 3′
3, 3a, 4
—
6.72 [H-2′, d, J(2′, 3′) = 8.0]
7.29 [H-3′, t, J(3′, 2′, 4′) = 7.6]
6.77 [H-4′, t, J(4′, 3′) = 7.3]
1.23
3.80
1′, 3′, 4′
1′, 2′, 4′
2′, 3′
3, 3a, 4
7
7.30 [H-3′, t, J(3′, 2′, 4′) = 7.9]
6.80 [H-4′, t]k
CH3
OCH3
1.31[s]
—
—
54.8
*In ppm from TMS. †13C, 1H HMBC connectivity. ‡H-1 and H-3 are diastereotopic protons. §N-H signal disappeared when D2O was added. kThe H-4′
triplet signal is overlapped by the H-9 doublet signal. The integration 2 corresponds to this couple of signals. ¶Negative phase in 13C NMR DEPT 135°
spectrum.
Figure 5. Signal assignation for 1H NMR spectrum in CD3CN for product 3e. Atom numbering is that shown in the structure and in Table 3. There is
a signal at 8.74 ppm, corresponding to NH at position 5, which disappears by adding D2O.
derivatives studied, supporting a radical chain reaction generating
PhNHCH2• radicals, hence explaining the larger Φpc for 1e–f.
lower for DABCO (8.1 9 107 to 9.2 9 108 Mꢀ1sꢀ1). These
quenching constants do not show dependency on the substitu-
ent’s nature. The obtained values are in line with the reported
oxidation potential of 0.99 and 0.60 V vs SCE for NPG (38) and
DABCO (40), respectively. Therefore, the quenching processes
should be mainly attributed to a one electron transfer from the
NPG or DABCO to the 1a–f excited triplet state with the genera-
tion of the corresponding radical ion pair. Figure 7 shows the
triplet–triplet transient absorption spectra obtained for derivative
Laser flash photolysis
All these quinoxalin-2-ones 1a–f show strong transients absorp-
tions between 350 and 450 nm that were quenched by NPG and
DABCO with rate constants close to diffusion limit (1.2 to
7.5 9 109 Mꢀ1 ꢀ1) for NPG and one or two magnitude order
s

1342 Julio R. De la Fuente et al.
105
N
H
N
R
O
H
N
R
O
N
N
N
3.+
m/z = M + 14
H
N
R
O
H
N
N
CH2=CH2
R
O
N
N
N
N
3.+
m/z = 119
m/z = 91
Scheme 2. Electronic impact fragmentation for products 3a–f.
0.05
3.0
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
2.5
2.0
1.5
1.0
0.5
0.0
800
780
760
740
720
0.04
0.03
0.02
0.01
0.00
-0.01
250 300 350 400 450 500
Wavelength
0.00 0.01 0.02 0.03 0.04 0.05
[H O] M
2
0.0
0.1
0.2
0.3
0.4
0.5
0.6
-0.02
300
350
400
450
500
550
600
650
700
[ 1d ] mM
Wavelength nm
Figure 6. Photoconsumption evaluated as (Abst=0 ꢀ Abst=20 min
) at:
336 nm (□), 290 nm (○) and 433 nm (D), corresponding to the nonsub-
stituted 3-methyl-quinoxalin-2-one 1d, N-phenylglycine (NPG) and peryl-
ene, respectively. The inset shows absorbance changes in the sensitized
photoreaction of 0.05 mM perylene, 0.9 mM NPG and 0.3 mM 1d. The
arrows show the direction of the absorbance changes.
Figure 7. Time-resolved absorption spectra for 1d excited state triplet
(□) 1.0 ls after the laser pulse with kmax = 410 nm; the anion radical
1d•ꢀ at kmax = 430 nm (○) generated in the presence of 1 mM DABCO
0.5 ls after the laser pulse; and the hydrogenated radical (H)1d• at
kmax = 380 nm (D) after 15 ls delay. The inset shows the effect of
[H2O] on the maximal absorption of (H)1d• at kmax = 380 nm.
1d in acetonitrile with a maximum at 400 nm, and the spectra
obtained in the presence of DABCO at delays of 0.5 and 15 ls
after the laser pulse with absorption maxima at 430 and 380 nm,
respectively. The spectra obtained in the presence of DABCO were
attributed to the radical anion 1d•ꢀ at 0.5 ls and to the (H)1d•
generated by proton transfer from adventitious water to 1d•ꢀ
after a 15 ls delay. The (H)1d• absorption band at 380 nm
increases when water is added to the acetonitrile confirming our
assignment, the [H2O] effect on DOD at 380 nm is shown in the
inset of Fig. 7. Similar behavior was observed for the other
derivatives and can be represented by Eq. (5).
1
ꢂꢀ þ Hþ ! ðHÞ1ꢂ
ð5Þ
In the presence of NPG, a more complex behavior was
observed, see Fig. 8; shortly after the laser shot, the transient

Photochemistry and Photobiology, 2013, 89 1343
0.06
0.05
0.04
0.03
0.02
0.01
0.00
-0.01
-0.02
0.012
0.010
0.008
0.006
0.004
0.002
0.000
-0.002
-0.004
-0.006
-0.008
-0.010
0.008
0.006
0.004
0.002
0.000
-0.002
-0.004
-0.006
0.000
-0.002
-0.004
-0.006
340 nm
0
20
40
60
80 s
0
10
20
30
40
t
μ
t
μ
s
[NPG] mM
0.0 0.2 0.4 0.6 0.8 1.0 1.2
1.25x105
1.00x105
k
4
obs 7.50x10
5.00x104
2.50x104
0.00
300
350
400
450
500
550
600
650
700
300
350
400
450
500
550
600
650
700
Wavelenght nm
Wavelenght nm
Figure 8. Transient spectra for 0.7 mM 1d in the presence of 1 mM NPG
at delays of: 0.5, 5 and 80 ls, (□), (○) and (D), respectively. The upper
inset shows the ground depletion at 340 nm and the lower inset shows
the effect of [N-phenylglycine] on the ground depletion pseudo first-order
Figure 9. Radical anion 1d•ꢀ (□) spectrum obtained in the presence of
DABCO; normalized spectrum of 1d in the presence of 1 mM N-phenyl-
glycine (NPG) (○) and the resulting spectrum after subtraction of 1d•ꢀ
(D); (D = ○ ꢀ □) showing the absorption of NPG•+ between 440 and
480 nm; a maximum at 360 nm attributed to (H)1d• and a shoulder at
410 nm and a not resolved absorption band with maximum below
320 nm attributed to PhNHCH2•. The inset shows the kinetics profiles of
1d in the presence of 1 mM NPG; from up to down at 430, 380, 460 and
340 nm, respectively.
rate constant decay kobs
.
spectrum shows a maximum at 430 nm, a secondary maximum
at 380 nm and a shoulder at 460 nm. During the first 5 ls, the
absorption at 460 nm increases showing the presence of at least
three species, while the kinetic traces at 430 and 380 nm evolve
differently. More interesting is the strong ground depletion
observed at 340 nm (upper inset in Fig. 8) that can be inter-
preted as showing the consumption of the ground state 1d.
Moreover, the decay rate of this ground depletion depends
strongly on the NPG concentration increasing with the [NPG] as
shown in the lower inset of Fig. 8. This plot was obtained by
adjusting pseudo first-order kinetics to the depletion.
To gain more insight for the spectral assignment, we com-
pared the spectra obtained at short time after the laser pulse in
the presence of DABCO and NPG subtracting the spectrum
attributed to 1d•ꢀ to the normalized spectrum obtained in pres-
ence of NPG. This difference spectrum, shown in Fig. 9, shows
a clear absorption between 440 and 480 nm which can be attrib-
uted to NPG•+ as was reported for the NPG radical cation in
water (26). With this absorption also appears a band with maxi-
mum at 360 nm which, based on the results in the presence of
DABCO and [H2O] effect, we assigned to the hydrogenated radi-
cal (H)1d•. This absorption appears shortly after the laser pulse
suggesting an early contribution of hydrogen transfer from the
NPG to the excited quinoxalin-2-one. This process, Eq. (6),
should lead to the hydrogenated radical (H)1d• and
PhNH-•CHCOOꢀ that after decarboxylation should lead to
PhNHCH2• (27,28).
ble to consider the presence of PhN•-CH2COOꢀ generated by de-
protonation of the NPG•+ (pKa = 7.35) (26). This radical has
similar absorption bands to those reported for PhNHCH2• (28)
and cannot be totally ruled out. However, although this radical
centered in N may be present, it cannot explain the formation of
products 2 and 3. Therefore, shortly after the pulse the absorp-
tion spectra in the presence of NPG should be mainly attributed
to the contributions of: 1d•ꢀ; NPG•+; (H)1d•; PhNHCH2• and
likely other unidentified species. It is worthy to note that the
absorption contributions that we attributed to: 1d•ꢀ; NPG•+ and
(H)1d• are still evident in the spectrum 80 ls after the laser
pulse as can be seen in Fig. 8.
The inset in Fig. 9 shows the decays at the wavelengths of
the different maxima and shoulders observed for the transient in
the presence of NPG. While in the first 5 ls it can be seen a sec-
ondary growth of the absorption attributed to NPG•+ at 460 nm
occurring simultaneously with the decay of (H)1d• at 380 nm,
suggesting that the formation of NPG•+ occurs by two ways: the
electron transfer from NPG to 1, Eq. (1) and the reaction of (H)
1d• and surplus NPG, Eq. (7), leading to metastable (H)1ꢀ,
which eventually will regenerate product 1 in a similar way to
that which we reported for 3-phenyl-quinoxalin-2-ones and
amines (19,20).
NPG þ ðHÞ1dꢂ ! NPGꢂþ þ ðHÞ1dꢀ
ð7Þ
31ꢃ þ PhNHCH2COOꢀ þ Hþ ! ðHÞ1 ꢂ þPhNHCH2ꢂ þCO2
ð6Þ
It is interesting to notice that the initial growth of the ground
depletion at 340 nm has the same profile of the NPG•+ growth,
suggesting that the reaction of 1d with the PhNHCH2• is able to
generate more NPG•+, see inset in Fig. 9. After delay times
>10 ls, a nearly parallel decay for all the absorptions monitored
can be observed. Moreover, the increasing ground depletion at
340 nm which follows after long delay times, strongly suggests
a chain radical reaction consuming the ground state 3-methyl-
In the difference spectrum, another strong absorption with a
maximum below 320 nm (below our experimental detection lim-
its) and a shoulder centered at 400 nm were observed and may
be tentatively identified with those reported for PhNHCH2• (28),
which are probably overlapped with the absorptions of other
transient species. Among the aforementioned species it is possi-

1344 Julio R. De la Fuente et al.
quinoxalin-2-one by PhNHCH2• leading to the products 2 and 3,
Eqs. (3) and (4). For all of the studied substrates 1a–f a com-
pletely analogous flash photolysis behavior was observed. The
time-resolved spectroscopic study will be published elsewhere.
Having two ways to generate NPG•+ and hence two
PhNHCH2• via the reactions of Eqs. (1) and (7) could account for
a maximal Φpc = 2, therefore other processes likely involving
PhNHCH2• and the ground state 1, probably contribute to the gen-
eration of more PhNHCH2• radicals. It is a well-known fact that
the a-aminoalkyl radicals are strong one electron reductants (41–
44), thus, they might to be able to reduce the quinoxalin-2-ones
generating the respective radical anions 1•ꢀ and a H+, Eq. (8), giv-
ing origin to (H)1•, which is able to oxidize NPG, Eq. (7).
contributing to the radical chain reaction. As we stated earlier,
the complete flash photolysis study will be published elsewhere.
Surprisingly, what looks like a simple photochemically initi-
ated radical addition reaction leads to the totally unexpected
annulation product 3 which were unequivocally characterized in
this work. As far as we know, there are no reports of photo-
chemical or radical reactions leading to similar annulations prod-
ucts. On the other hand, the large quinoxalin-2-one
photoconsumption quantum yields observed for the F-, H-, CF3-,
and CN-derivatives, see Table 1, require a chain radical reaction
able to generate NPG•+ and hence PhNHCH2•. We propose four
possible paths for these radical propagation reaction: (H)1•
abstracting electrons from NPG, Eq. (7); 1 abstracting electron
from PhNHCH2•, Eq. (8); and the electron and/or hydrogen
abstraction from NPG by the intermediaries addition radicals
which leads to products 2 and 3. Thus, the greater the 3-methyl-
quinoxalin-2-one substituent electron-withdrawing power, the
more easy should be the electron abstraction from the NPG or
PhNHCH2• explaining the observed Hammett correlation of
photoconsumption yields.
PhNHCH2 ꢂ þ1 ! PhN ¼ CH2 þ ðHÞ1ꢂ
ð8Þ
Moreover, the intermediate radicals leading to products 2 and
3 probably are also able to oxidize NPG contributing to the
chain reaction.
These preceding reactions may rationalize the almost parallels
decays observed for all the transient species at longer times after
the laser pulse and the increasing consumption of the ground
state 3-methyl-quinoxalin-2-one with [NPG], see inset in Figs. 8
and 9. The electron abstraction of processes 7 and 8 generating
PhNHCH2• can explain the Hammett correlation with r+, being
the most electron-withdrawing substituent those which more eas-
ily should abstract an electron from PhNHCH2• or NPG.
Therefore, photolysis of common reactants widely used as
NPG and substituted quinoxalin-2-ones may provide a synthetic
way to the unusual, substituted imidazoquinoxalinones 3a–f that
has never been reported.
Acknowledgements—We thank Dr. Gordon L. Hug for his careful reading
~
of the manuscript; Prof. Dr. F. Castaneda M. for valuable discussion and
advice; thanks are also due to F. Morales from Del Carpio Analysis for
the tandem MS–MS spectra; and to B. Sepulveda from CEPEDEQ, U.
de Chile for the CI GC-MS analysis; and to FONDECYT grant 1100121
for the financial support. C. Aliaga acknowledges the FONDECYT grant
3130697.
By considering the flash photolysis results, the lack of the reac-
tions in oxygenated samples, the structures of the products, the
high photoconsumption quantum yields and the Hammett correla-
tion, which can be explained only by considering a radical chain
reaction, a reaction mechanism can be proposed. It should include
a photoinduced one electron transfer from NPG to excited triplet
quinoxalin-2-ones, 31, Eq. (1), generating the radical ion pair,
which should lead to (H)1• and PhNHCH2•, Eq. (2), and a com-
petitive hydrogen transfer, Eq. (6), leading to the same radical
pair. These radicals can combine in a termination reaction to prod-
uct 2, Eq. (3), or initiate the chain propagation reactions of
Eqs. (7) and (8). The consumption of two PhNHCH2• by reactant
1, would terminate the radical propagation leading to product 3,
Eq. (4). Other termination steps, explaining the formation of
(PhNHCH2)2 and, PhN=CH2 and PhNHCH3, by radical addition
or hydrogen transfer, respectively, might also be considered.
SUPPORTING INFORMATION
Additional Supporting Information may be found in the online
version of this article:
Data S1. 1H and 13C NMR and MS for compound 1a–f; EI
MS chromatograms for products 2a–f and 3a–f; and 1H, 13C
NMR 1D and 2D spectra for products 3a and e, can be found at
DOI: 10.1111/php.12162
CONCLUSIONS
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Photoreaction between the 7-substituted-3-methyl-quinoxalin-2-
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identified by CI mass spectra. We were not able to find literature
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evidence, seems reasonable.
The flash photolysis results presented here provide evidence
for almost all of the proposed intermediaries and strongly support
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addition intermediaries that likely are able to oxidize NPG
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