(Co)oxidation/cyclization processes upon irradiation of triphenylamine

Article abstract of DOI:10.1016/j.tetlet.2014.03.086

Irradiation of triphenylamine (Ph₃N) in nitrogen-flushed solution leads to 9-phenylcarbazole and two tetrahydroderivatives (1,2,3,4- and 1,2,7,8-) via disproportionation of the corresponding 4a,4b-dihydrocarbazole. In oxygen-equilibrated solution oxidative cyclization occurs through the intermediacy of a triplet peroxy diradical, which either abstracts a hydrogen atom intramolecularly or (mainly) cleaves back to the reagents. The role of the key intermediates is supported by DFT calculations and by trapping by triarylphosphines (that are thus efficiently oxidized, while preventing the cyclization of Ph₃N). The hydroperoxide, on the other hand, causes inefficient co-oxidation of sulfides.

Full text of DOI:10.1016/j.tetlet.2014.03.086

Tetrahedron Letters 55 (2014) 2932–2935
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
(Co)oxidation/cyclization processes upon irradiation of
triphenylamine
a
a
a
a,
Sergio Mauricio Bonesi a,b, , Daniele Dondi , Stefano Protti , Maurizio Fagnoni , Angelo Albini
⇑
⇑
a PhotoGreen Lab, Department of Chemistry, University of Pavia, V. Le Taramelli 12, 27100 Pavia, Italy
b CIHIDECAR–CONICET, Department of Organic Chemistry, FCEyN University of Buenos Aires, 3er Piso, Pabellón 2, Ciudad Universitaria, CP1428 Buenos Aires, Argentina
a r t i c l e i n f o
a b s t r a c t
Article history:
Irradiation of triphenylamine (Ph3N) in nitrogen-flushed solution leads to 9-phenylcarbazole and two
tetrahydroderivatives (1,2,3,4- and 1,2,7,8-) via disproportionation of the corresponding 4a,4b-dihydroc-
arbazole. In oxygen-equilibrated solution oxidative cyclization occurs through the intermediacy of a
triplet peroxy diradical, which either abstracts a hydrogen atom intramolecularly or (mainly) cleaves
back to the reagents. The role of the key intermediates is supported by DFT calculations and by trapping
by triarylphosphines (that are thus efficiently oxidized, while preventing the cyclization of Ph3N). The
hydroperoxide, on the other hand, causes inefficient co-oxidation of sulfides.
Received 28 January 2014
Revised 14 March 2014
Accepted 18 March 2014
Available online 29 March 2014
Keywords:
Photooxidation
Photocyclization of triphenylamine
Phosphine oxidation
Sulfide oxidation
Ó 2014 Elsevier Ltd. All rights reserved.
The electrocyclic rearrangement of stilbene and related aryl-al-
kenes is of great interest both as a synthetic approach to polycyclic
derivatives and for the mechanistic issues involved.1 This is prob-
ably the most in-depth studied reaction where photochemical
and thermal processes follow opposite stereochemical courses,1a
leading to either trans or cis relationship of the substituents at
the ring fusion positions. When these are hydrogen atoms, oxida-
tion may follow and leads to an aromatic derivative.1c Hetero-
compound)2e,3 led to trans-N-phenyl-4a,4b-dihydrocarbazole in
the triplet state (represented by the diradical formula 3DHC,11 path
a, Scheme 1) and this in turn crossed (path b) over to the singlet
ground state, more stable by 3.9 kcal molÀ1 (represented as
DHC0).12 The last intermediate had a zwitterionic rather than
diradical character and it was remarked that this was consistent
with the fact that no spin trapping occurred in the presence of
5,5-dimethyl-1-pyrroline-N-oxide and N-tert-butyl-a-phenylnit-
atom-containing analogs of stilbene and other
6
p
electrons
rone.11,13 It was formed efficiently, but mainly reverted back to
Ph3N (path d, >90%) and only in part underwent disproportionation
(path c) to carbazole (NPC) and a tetrahydrocarbazole (H4-NPC, of
structure not known, notice that analogous N-methyldiphenyl-
amine2a gives the 1,2,7,8-derivative).
systems have been likewise studied intensively and are of equal
interest on the same grounds. An example is the photocyclization
of di-2–4 and tri-phenylamines3–5 that leads to dihydrocarbazoles,
some of which are present among natural products,6 or, by oxida-
tion, to carbazoles, a class of heterocycles often employed in
drugs,7 dyes,8 photoactive polymers,9 and, OLEDs.10 In particular,
the photocyclization of triphenylamine (see Scheme 1) to 9-
phenylcarbazole (NPC) has been reported2e,3 in different organic
solvents. From the mechanistic point of view, electrocyclic photo-
cyclization is one of the few cases where the adiabatic course of a
photoreaction (from the excited state of the reagent to the excited
state of the product) has been documented. Thus, both time
resolved spectroscopy analyses5,11 and a computational investiga-
tion by the AM1-SCI method supported that cyclization from 3Ph3N
(singlet–triplet intersystem crossing is almost quantitative in this
In the presence of oxygen, aromatization of DHC0 to NPC oc-
curred. It was found that the quantum yield of the oxidative cycli-
zation (Ucy) increased from 0.04 to 0.09 (depending on the nature
of the solvent) when changing from oxygen-free conditions to ca.
0.2 in air equilibrated solution.3 Potentially, oxygen may interact
with all of the sequentially formed intermediates, 3Ph3N, 3DHC,
and DHC0, and the overall yield appeared to result from the bal-
ance between quenching of 3Ph3N by molecular oxygen (producing
1O2, with
U
= 0.63 in benzene)14 and the intervention of O2 medi-
ated paths making more efficient the formation of NPC. Hydrogen
peroxide was also formed.3 Understanding the role of oxygen in
the aromatization step deserved, we thought, further attention,
also because it seemed possible that some intermediates generated
may oxidize other compounds under mild conditions. In view of
the above, we decided to further pursue this issue and report
⇑
Corresponding authors. Tel.: +39 0382 987316; fax: +39 0382987323.
E-mail addresses: smbonesi@qo.fcen.uba.ar (S.M. Bonesi), angelo.albini@unipv.it
(A. Albini).
http://dx.doi.org/10.1016/j.tetlet.2014.03.086
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

S. M. Bonesi et al. / Tetrahedron Letters 55 (2014) 2932–2935
2933
amount of highly polar products. In order to understand the mech-
anism of the oxidative photocyclization, the photoreaction of Ph3N
in the presence of potential oxygen acceptor was investigated. Sul-
fides and phosphines were chosen as suitable probes (see
Scheme 3). The results are reported in Tables 1 and 2 and can be
summarized as follows. Sulfides were co-oxidized to sulfoxides at
a rate dependent on structure and conditions. The rate of the tri-
phenylamine oxidative cyclization increased to a various extent
(10–250%) and the rate ratio of sulfoxide versus carbazole forma-
tion was P1 (from ca. 1.1 to 2.5). In contrast, irradiation of triphen-
ylamine in the presence of either triphenylphosphine or tris-(2-
methylphenyl)phosphine led to the corresponding phosphine oxi-
des, but at the same time the formation of N-phenylcarbazole (1)
was completely inhibited. A precise comparison between the oxi-
dation rate of sulfides and phosphines was not feasible, since dif-
ferent irradiation conditions had to be adopted to avoid auto-
oxidation of phosphines, but it was clear that the photooxidation
of the latter substrates was at least five times faster than either
oxidation of sulfides or oxidative photooxidation of TPA alone.
These results pointed to the involvement of different intermediates
in the reaction of the two traps.
H
H
a
d
3Ph3N
.
.
N
Ph
3DHC
b
hν
H
H
C-
N+
Ph3N
DHC0
Ph
c
N
Ph
NPC
H4-
NPC
Scheme 1. Photochemical cyclization of triphenylamine (Ph3N).
below a combined experimental and computational investigation
about the photocyclization of triphenylamine in different solvents
and in the presence of oxidation-liable substrates.
Energy transfer to give singlet oxygen is energetically viable
only by quenching of 3Ph3N (see above)14 and not from 34, due
to the low energy gap of the latter from ground state 14, much be-
low that required for 1O2 formation (ca. 22 kcal molÀ1).15a If these
were the only effect by oxygen, it would lead to quenching of the
cyclization and oxygenation of the additives.15b,c The following evi-
dences suggested that this was not a singlet oxygen reaction, how-
ever: (1) thus, under bona fide 1O2 conditions, ring-substituted
triphenylphosphines are known to give phosphinates along with
phosphine oxides,16 contrary to what observed in the present case
(see Table 1); (2) as for sulfides, sulfones are known to always
accompany the sulfoxides, at least in polar aprotic and non-polar
solvents, and benzyl sulfides do undergo both sulfoxidation and
oxidative cleavage to benzaldehyde in protic media, again differ-
ently from what observed under the present conditions (see
Table 2).17 An alternative mechanism is that the diradical character
of dihydrocarbazole 34 makes viable a chemical quenching of the
intermediate by molecular oxygen (path e in Scheme 3). Actually,
the interaction of 34 with ground state (triplet) oxygen can result
in a singlet, a triplet, or a quintet. Computing the energy of all of
the possible combinations demonstrated that the most favored
path led to a chemically bonded adduct with triplet multiplicity
that was formed through an almost thermoneutral process
In our hands, irradiation of a nitrogen-flushed 1 Â 10À2
M
acetonitrile solution of Ph3N led to N-phenylcarbazole (1) as the
main product (53%) along with two tetrahydro-derivatives that
were spectroscopically identified (see Scheme 2) as N-phenyl-
1,2,7,8-tetrahydro- (2, 14%) and N-phenyl-1,2,3,4-tetrahydrocar-
bazole (3, 5%), containing respectively a doubly conjugated pyrrole
and an indole aromatic system. Compounds 1–3 obviously arose
from a dihydrocarbazole intermediate (4) the role of which was
assessed by means of a DFT computational study at the (U)B3LYP
level of theory, by using the integral equation formalism model
(IEFPCM) for the solvent (acetonitrile). The Pople’s basis set
6-311++G(2d,p) was adopted for all atoms (see ESI for further
details). This essentially confirmed the AM1-SCI results, though
with some differences in the electronic distribution. Thus, singlet
14 had a purely zwitterionic character (a mixture of two predomi-
nant mesoionic structures, as indicated in Scheme 2) and lay a
mere 3.4 kcal molÀ1 below the triplet 34 (of diradical character,
satisfactory represented by the single formula in Scheme 2). As
mentioned, rearrangement to 34 and ISC to 14 mainly led to retro-
cyclization to triphenylamine (path d). No intramolecular con-
certed path leading to an aromatic system was available and
reasonably intermolecular hydrogen transfer took place leading
to radicals 5 and 6 and to the observed products 1–3 from them.
The corresponding experiment with an oxygen-equilibrated
solution gave 1 as the only isolated product, along with a small
(D
G° = 0.24 kcal molÀ1, through a transition state that was located
at 6.7 kcal molÀ1,see Scheme 4). More precisely, taking into
account both the regiochemistry and the stereochemistry of such
H
H
H
H
H
H
.
H
c
a
3Ph3N
+
.
N
.
N
Ph
.
6
N
Ph
5
Ph
34
b
H
H
H
H
H
H
CH-
hν
C-
N+
Ph
H
N+
Ph
N
Ph
H
H
H
3
14
N
Ph
H
H
d
H
N
Ph
H
2
1, NPC
H
H
Ph3N
Scheme 2. Cyclization of Ph3N under O2-free conditions.

2934
S. M. Bonesi et al. / Tetrahedron Letters 55 (2014) 2932–2935
.
O
HO
H
O
H
O
H
H
.
H
H
H
O2
e
.
N
Ph
N
f
.
N
37
8
34
Ph
Ph
g
R2S
Ar3P
Ar3PO
Ar3P
h
j
- H2O2
R2SO
.
O
HO
H
H
Ar3PO
H
-H2O
N
14
Ph3N
i
Ph
k
N
N
10
1
Ph
9
Ph
Scheme 3. Proposed mechanism for the co-oxidation of triphenylphosphine and sulfides during the photocyclization of triphenylamine.
Table 1
a
Rates of co-oxidation of aryl sulfides (
l
mol minÀ1) upon irradiation in the presence of Ph3N; in parentheses, the amount of N-phenylcarbazole (1) formed (
l
mol minÀ1
)
MeCN
MeCN/H2O 9/1
TFE
CH2Cl2
(.104)
Neat solvent
(.049)
(.16)
(.43)
PhSMe ? PhSOMe
.029(.075)
.075 (.11)
.21 (.096)b
.023 (.13)
.17 (.21)
.31 (.24)
.48 (.20)
<.01 (.19)
0.53 (0.19)
.24 (.074)
.22 (.075)
.013 (.042)
.087 (.11)
.17 (.13)
.45 (.10)
4-MeOC6H4SMe ? 4-MeOC6H4SOMe
PhCH2SEt ? PhCH2SOEt
Ph2S ? Ph2SO
.031 (.098)
a
5 Â 10À3 M solution of Ph3N irradiated in the presence of the chosen sulfide (10À2 M) at 366 nm (4 Â 15 W phosphor-coated lamps).
b
PhCHO (.091 l
mol minÀ1) was also observed.
Table 2
Rates of co-oxidation of aryl phosphines
presence of Ph3N; in parentheses, the amount of N-phenylcarbazole
mol minÀ1
)
upon irradiation in the
formed
adducts, six isomeric structures can be envisaged for this reaction
(see Figs. S1–S6 in the Supplementary information). The most sta-
ble isomer resulted from attack at position 3 (diradical 37 in
Schemes 3 and 4). In turn, the generated intermediate could
undergo intramolecular hydrogen abstraction and give a hydroper-
(
l
1
a
(l )
mol minÀ1
MeCN
0.121 (À) 0.188 (À)
(o-Tol)3P ? (o-tol)3PO 0.042 (À) 0.052 (À)
MeCN/H2O 9/1 TFE
CH2Cl2
Ph3P ? Ph3PO
0.033 (À) 0.091 (À)
0.049 (À) 0.054 (À)
oxide (8, path
f in Scheme 3) through a largely exergonic
(À38.2 kcal molÀ1) process (see Scheme 4).
a
5 Â 10À3 M solution of Ph3N irradiated in the presence of the chosen phosphine
The obtained hydroperoxide underwent aromatization by
hydrogen peroxide elimination (path g), a process presumably
encountering a significant barrier and occurring at room tempera-
ture a rather slow radical chain mechanism.18 In the presence of
sulfides, however, oxygen transfer to form sulfoxides occurred
and the resulting hydroxy derivative 9 (path h) underwent dehy-
dration to give carbazole 1. Thus, with sulfide dihydrocarbazole
aromatization and donor oxidation were coupled and the result de-
pended on the nature of the substrate (e.g., diphenylsulfide was
much less efficient than a mixed aromatic–aliphatic sulfide or a
dialkyl sulfide such as PhCH2SCH2CH3, see Table 1). On the other
hand, the precursor of hydroperoxide 8, viz. diradical 7, was an-
other potential oxygen-donating species. It appears reasonable
that the more nucleophilic phosphines were able to trap such rad-
icals in efficient competition with intramolecular H-abstraction
(path j vs path f). Indeed, the reactivity of peroxy radicals with
phosphines has been previously demonstrated.19a As an example,
oxidation of triphenylphosphine by t-butylperoxide occurs at a
rate of 102 MÀ1 sÀ1 at room temperature more than two orders of
(10À2 M) at 366 nm (focalized, filtered light; under these conditions no oxidation of
the phosphine took place in the absence of triphenylamine).
.
.
3DHC -O2
O2
+6.7
37
(
)
34
14
+0.2
-38.2
+3.4
3DC-O2H (
-47.3
)
38
PPh3
-57.8
PPh3O
+0.2
18
(
)
.
-44.4
H2O2
DHC-O
10
(
)
magnitude larger than that with sulfides (0.73 MÀ1 sÀ1 19b
and
)
1
PPh3
-52.5
PPh3O
likewise catalyzed oxidation by hydrogen peroxide is markedly
faster.20 Also in this case, DFT calculations were carried out and
demonstrated that in the presence of phosphines oxygen transfer
both from diradical 7 and from the resulting radical 10 is strongly
14
Scheme 4. Energy change in the observed reactions (values in kcal molÀ1).
Ph3N
exergonic (path j and k,
tively, the PAO bond formation being the driving force of the
D
G° = À71.3 and À45.5 kcal molÀ1 respec-

S. M. Bonesi et al. / Tetrahedron Letters 55 (2014) 2932–2935
2935
process). Thus, two oxygen atoms were sequentially transferred to
References and notes
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N-methyl-N,N-diphenyl amine, see Ref. 2c.
In conclusion, triplet dihydrocarbazole (34) adds O2 to form two
potentially oxidizing species. The first formed peroxy diradical (7)
has a strong electrophilic character, but a short lifetime due to the
decay to 14, and is trapped by nucleophilic phosphines to which
both atoms of oxygen are transferred. Notice that the structure of
peroxy diradical 7 corresponds to the chemical (rather than phys-
ical) activation of oxygen as originally formulated by Schenck for
photosensitized
O–OÅ).21 Sulfides are poor traps and in that case rearrangement of
short-lived 7 to hydroperoxide occurs faster than oxygen
oxidations
(Sens + hm
? ÅSensÅ + O2 ? ÅSens-
8
transfer. Sulfides do trap a persistent intermediate such as 8 and
subsequent dehydration leads to aromatized 1. Thus oxidative
cyclization and sulfide co-oxidation are coupled. The results ob-
tained may have a potential significance from both the synthetic
and mechanistic point of view. In fact, the Ph3N oxidative cycliza-
tion follows a complex path and involves various active intermedi-
ates that may find application in organic synthesis, for example for
the selective oxidation of poly-functionalized compounds.
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Acknowledgements
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2001, 3, 3719–3722; Zhang, D.; Celaje, J. A.; Agua, A.; Doan, C.; Stewart, T.;
Selke, M. Org. Lett. 2010, 12, 3100–3103.
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Org. Chem. 1999, 1723–1728; Clennan, E. L. Acc. Chem. Res. 2001, 34, 875–884.
18. Hermans, I.; Peeters, J.; Jacobs, P. A. Top. Catal. 2008, 50, 124–132.
19. See for instance (a) Lalevée, J.; Allonas, X.; Fouassier, J. P. Chem. Phys. Lett. 2007,
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Chem. Soc. 2003, 125, 9074–9082.
S.M. Bonesi is a research member of CONICET. S. Protti acknowl-
edges MIUR, Rome (FIRB-Futuro in Ricerca 2008 project
RBFR08J78Q) for financial support. D. Dondi gratefully acknowl-
edges the CINECA Supercomputer Center, with computer time
granted by the COSBIM project (HP10CEY2LM). We are grateful
to F. Corana and B. Mannucci (Centro Grandi Strumenti, University
of Pavia) for precious help.
20. The oxidation of aromatic sulfides via hydrogen peroxide has found to proceed
inefficiently, see Du G.; Espenson, J. H. Inorg. Chem. 2005, 44, 2465-2461; on the
other hand, even if the oxidation of phosphines with H2O2 has been described,
see Abu-Omar M. M.; Espenson, J. H. J. Am. Chem. Soc. 1995, 117, 272-280, in
our case the formation of the oxidant occurs only along with Ph3N
photocyclization, a process not taking place with phosphines.
21. Schenck, G. O.; Kinkel, K. G.; Koch, E. Naturwissensch 1954, 41, 425.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.03.
086.