The unexpected conversion of a thiophene ring into a pyrrole ring via a putative nitrene intermediate

Article abstract of DOI:10.1016/j.tetlet.2012.02.050

Triethylphosphite induced reductive cyclisation of 1-(2-nitrophenyl)-3,5- di(2-thienyl)pyrazole 6 afforded the expected 1,3-di(2-thienyl)pyrazolo[1,2-a] benzotriazole 7 (14%) together with an unexpected product which was shown to be a 2-(2-thienyl)pyrazolo[1,5-a]pyrrolo[2,1-c]quinoxaline 8 derivative (27%). A mechanism for the extrusion of sulfur during the transformation of heterocycle 6 into product 8 is proposed.

Full text of DOI:10.1016/j.tetlet.2012.02.050

Tetrahedron Letters 53 (2012) 2111–2113
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
The unexpected conversion of a thiophene ring into a pyrrole ring
via a putative nitrene intermediate
Ross W. Harrington a, Stephen P. Stanforth b,
⇑
a School of Chemistry, Bedson Building, Newcastle University, Newcastle-upon-Tyne, NE1 7RU, UK
b School of Life Sciences, University of Northumbria, Newcastle-upon-Tyne, NE1 8ST, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Triethylphosphite induced reductive cyclisation of 1-(2-nitrophenyl)-3,5-di(2-thienyl)pyrazole 6 affor-
ded the expected 1,3-di(2-thienyl)pyrazolo[1,2-a]benzotriazole 7 (14%) together with an unexpected
product which was shown to be a 2-(2-thienyl)pyrazolo[1,5-a]pyrrolo[2,1-c]quinoxaline 8 derivative
(27%). A mechanism for the extrusion of sulfur during the transformation of heterocycle 6 into product
8 is proposed.
Received 14 December 2011
Revised 31 January 2012
Accepted 10 February 2012
Available online 17 February 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Heterocyclic mesomeric betaines
Reductive cyclisation
Nitrenes
Pyrazolo[1,2-a]benzotriazole
Pyrazolo[1,5-a]pyrrolo[2,1-c]quinoxaline
Thiophenes
Polythiophenes
The synthesis and properties of thiophene-containing conduct-
ing polymers have attracted considerable interest.1–4 We recently
reported the synthesis of monomer 1 and have studied its electro-
polymerisation which yielded a polymer with optical and electro-
chemical band-gaps of 2.35 and 2.34 eV, respectively.5 Monomer 1
is an example of a Type B heterocyclic mesomeric betaine (HMB)6
and as such, is associated with the general core structure in which
the heteroatoms X and Y are located at the bridge-head positions
In view of our interest in thiophene-containing Type B HMBs as
precursors to potential low band-gap polymers, we report in this
Letter an investigation of the reductive cyclisation of compound
6 as a potential route to the Type B HMB 7.
S
O
+
S
_
+
_
N
N
N
N
O
X
_
and formally contribute a pair of electrons to the
p-system as
_
+
N
N
depicted in formula 2. The polymer derived from monomer 1 is, to
our knowledge, the first example of a thiophene-containing mate-
rial built upon a Type B HMB scaffold. In contrast to Type B HMBs,
the Type A HMBs are associated with heteroatoms X and Y that
are located at non-bridgehead positions as shown in formula 3. Sev-
eral examples of thiophene-containing conducting polymers which
possess this structural motif have been reported such as polymers
derived from the thienyl-substituted thieno[3,4-c][1,2,5]thiadia-
zole 4 (Eg = 0.9 eV)7 and related systems.8 An important feature of
both Type A and Type B HMBs is that their highest occupied molec-
ular orbital is topologically and energetically similar to a non-
bonding molecular orbital.6 Consequently, the frontier molecular
orbital energy separation in these systems is relatively small and
this property can be used beneficially for the construction of low
band-gap polymers such as those noted above.
+
S
X
Y
S
O
S
O
Y
Type A
3
Type B
2
S
1
4
The reaction of compound 59 with 2-nitrophenylhydrazine afforded
1-(2-nitrophenyl)-3,5-di(2-thienyl)pyrazole (6) (Scheme 1).10 In
view of several known examples of the triethylphosphite mediated
reductive cyclisations of 1-(2-nitrophenyl)pyrazole derivatives
yielding Type B HMBs based upon the pyrazolo[1,2-a]benzotriazole
ring system,11 heterocycle 6 was treated with hot triethylphosphite
with the expectation that the required Type B HMB 7 would be
formed. However, two products were formed from this reaction;
the required pyrazolo[1,2-a]benzotriazole HMB derivative 7 was
produced as anticipated together with an unexpected product which
⇑
Corresponding author. Tel.: +44 191 227 4784; fax: +44 191 227 3519.
E-mail address: steven.stanforth@northumbria.ac.uk (S.P. Stanforth).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.02.050

2112
R. W. Harrington, S. P. Stanforth / Tetrahedron Letters 53 (2012) 2111–2113
O2N
O
O
_
S
N
S
(i)
(ii)
N
N
+
N
N
N
+
N
S
N
S
S
S
S
5
6
7
8
Scheme 1. Synthesis of heterocycles 7 and 8. Reagents and conditions: (i) 2-nitrophenylhydrazine, AcOH, EtOH, concd H2SO4 (cat.), reflux (33%); (ii) P(OEt)3, 110 °C, 28 h [7
(14%) + 8 (27%)].
Figure 1. X-ray crystal structure of heterocycle 8 (ORTEP representation). Ellipsoids are shown at the 50% probability level.
was identified as 2-(2-thienyl)pyrazolo[1,5-a]pyrrolo[2,1-c]quinox-
aline (8).12 The structure of compound 8 was confirmed by X-ray
crystallography (Fig. 1).13 The asymmetric unit consists of two crys-
tallographically independent molecules, in an approximately copla-
nar arrangement. Both molecules are completely planar and pack
with a herringbone style arrangement, forming five intermolecular
line 13 and some related derivatives have been reported re-
cently as conformationally restricted 2,20-bipyrrole analogues.14
In conclusion, we have prepared a novel heterocyclic ring
system which has been formed by an unexpected mechanism.
A
thiophene ring has effectively been converted into a
pyrrole-ring during this process. The Type B HMB 7 has been
successfully prepared but in view of its relatively low yield
and the requirement of chromatography for its purification,
C–Hꢀ ꢀ ꢀp interactions.
A plausible mechanism which accounts for the formation of
heterocycle 8 is depicted in Scheme 2. Reduction of the nitro com-
pound 6 by triethylphosphite gives a putative intermediate nitrene
9 (or an equivalent species) from which the HMB 7 is formed by
nitrogen–nitrogen bond formation. In order to account for the for-
mation of heterocycle 8, the electrophilic nitrene 9 might also have
reacted at the 2-position of the appositely located electron-rich
thiophene ring yielding a dipolar intermediate 10 from which the
bridged sulfide 11 is formed (Scheme 2). Extrusion of sulfur from
compound 11, presumably by its reaction with triethylphosphite,
then affords the heterocycle 8.
this heterocycle is unlikely to find use as
precursor.
a
polythiophene
X
N
N
12
X = N
To our knowledge, compound 8 is the first example of a
derivative of the novel pyrazolo[1,5-a]pyrrolo[2,1-c]quinoxaline
heterocyclic ring system 12. The dipyrrolo[1,2-a:20,10-c]quinoxa-
13 X = CH
P(OEt)3
N
N
N
_
N
N
S
N
N
N
N
N
N
N
S
S
S
+
S
S
S
S
P(OEt)3
11
8
9
10
Scheme 2. Proposed mechanism for the formation of heterocycle 8.

R. W. Harrington, S. P. Stanforth / Tetrahedron Letters 53 (2012) 2111–2113
2113
EtOH gave compound 6 as maroon coloured needles (3.6 g, 33%), mp 122–
123 °C; 1H NMR (270 MHz, CDCl3) d 8.02 (1H, dd, J = 2 and 8 Hz), 7.55–7.72
(3H, m), 7.41 (1H, dd, J = 1.5 and 4 Hz), 7.28 (2H, dt, J = 1.5 and 6 Hz), 7.07 (1H,
dd, J = 6 and 8 Hz), 6.93 (1H, dd, J = 6 and 8 Hz), 6.84 (1H, dd, J = 1.5 and 4 Hz),
6.81 (1H, s); HRMS (ESI) C17H12O2N3S2 [M+H]+: calculated 354.0365, measured
354.0370.
Acknowledgments
We thank the EPSRC for an equipment grant for the X-ray dif-
fractometer and also the EPSRC National Mass Spectrometry Cen-
tre, Swansea, for high-resolution mass spectra.
11. See for example: Lynch, B. M.; Hung, Y.-Y. J. Heterocycl. Chem. 1965, 2, 218–219;
Lindley, J. M.; McRobbie, I. M.; Meth-Cohn, O.; Suschitzky, H. J. Chem. Soc.,
Perkin Trans. 1 1980, 982–994; Albini, A.; Bettinetti, G. F.; Minoli, G. J. Org.
Chem. 1983, 48, 1080–1083.
References and notes
12. A mixture of compound 6 (1.0 g, 2.8 mmol) and P(OEt)3 (3.0 mL) was heated
(110 °C, 28 h) with stirring under nitrogen atmosphere. The mixture was
allowed to cool to room temperature and the excess P(OEt)3 was evaporated
under reduced pressure (Kugelrohr). The resulting dark residue was purified by
column chromatography [silica gel; eluent EtOAc: petroleum ether (bp 40–
60 °C), 1:10 changing to 1:5] giving a yellow solid (0.35 g) which was shown to
be a mixture (approximately 4:7) of compounds 7 (14%) and 8 (27%) by 1H
NMR spectroscopy. Chromatography over silica gel eluting with CH2Cl2
enabled the separation of analytical samples of pure products. Compound 7
(ca. 20 mg, eluted second): mp 178–180 °C; 1H NMR (270 MHz, CDCl3) d 7.91
(1H, dd, J = 2 and 4 Hz), 7.79 (1H, br d, J = 11 Hz), 7.67 (1H, br d, J = 11 Hz),
7.45–7.49 (2H, m), 7.32–7.43 (2H, m), 7.17–7.25 (2H, m), 7.02 (1H, s), 6.96 (1H,
dt, J = 1.5 and 11 Hz); HRMS (APCI) C17H12N3S2 [M+H]+: calculated 322.0467,
measured 322.0469. Compound 8 (ca. 60 mg, eluted first): mp 192–193 °C; IR
1. Roncali, J. Chem. Rev. 1997, 97, 173–206. and references cited therein.
2. Schopf, G.; Koßmehl, G. Polythiophenes
– Electrically Conductive Polymers;
Springer, 1997.
3. Tourillon, G. In Handbook of Conducting Polymers; Skotheim, T. A., Ed.; Marcel
Dekker, 1986; Vol. 1, p 293.
4. Andersson, M. R.; Thomas, O.; Mammo, W.; Svensson, M.; Theander, M.;
Inganäs, O. J. Mater. Chem. 1999, 9, 1933–1940. Feature article on
polythiophenes designed for optoelectronic devices and conductors.
5. Elmasly, S.; Gehre, A.; Skabara, P. J.; Stanforth, S. P.; Vilela, F. Tetrahedron Lett.
2011, 52, 526–529.
6. Ramsden, C. A. Tetrahedron 1977, 33, 3193–3202.
7. Tanaka, S.; Yamashita, Y. Synth. Met. 1993, 55–57, 1251–1254.
8. See for example: Yamashita, Y.; Ono, K.; Tomura, M.; Tanaka, S. Tetrahedron
1997, 53, 10169–10178; Karikomi, M.; Kitamura, C.; Tanaka, S.; Yamashita, Y. J.
Am. Chem. Soc. 1995, 117, 6791–6792; Stecklet, T. T.; Abboud, K. A.; Craps, M.;
Rinzler, A. G.; Reynolds, J. R. Chem. Commun. 2007, 4904–4906; Kono, T.;
Kumaki, D.; Nishida, J. i.; Tokito, S.; Yamashita, Y. Chem. Commun. 2010, 46,
3265–3267; Tanaka, S.; Yamashita, Y. Synth. Met. 1995, 69, 599–600;
Mikroyannidis, J. A.; Tsagkournos, D. V.; Sharma, S. S.; Vijay, Y. K.; Sharma, G.
D. J. Mater. Chem. 2011, 21, 4679–4688.
(diamond anvil): m
max/cmꢂ1 1630, 1494, 1382, 1343; 1H NMR (270 MHz, CDCl3)
d 8.42 (1H, m), 7.72 (1H, m), 7.64 (1H, dd, J = 2 and 4 Hz), 7.50 (1H, dd, J = 1.5
and 3.5 Hz), 7.35–7.41 (2H, m), 7.32 (1H, dd, J = 2 and 8 Hz), 7.11 (1H, dd, J = 6
and 8 Hz), 6.81 (1H, s), 6.74 (1H, dd, J = 1.5 and 4 Hz), 6.67 (1H, dd, J = 3 and
4 Hz); 13C NMR (100 MHz, CDCl3) d 149.7, 136.3, 133.6, 127.7, 126.0, 125.7,
125.6, 125.3, 125.3, 125.0, 121.6, 117.1, 114.9, 114.1, 112.9, 104.8, 95.6; HRMS
(ESI)
C
17H12N3S [M+H]+: calculated 290.0746, measured 290.0749.
9. Ishii, A.; Nakayama, J.; Kazami, J-i.; Ida, Y.; Nakamura, T.; Hoshino, M. J. Org.
Chem. 1991, 56, 78–82.
Intermediate fractions contained a mixture of products 7 and 8.
13. Recrystallisation (MeOH) of a sample of compound 8 gave crystals suitable for
X-ray analysis. Crystallographic data have been deposited with the Cambridge
Crystallographic Data Centre, CCDC857991. Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
[Fax: (international) +44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk].
14. Matsumoto, S.; Qu, S.; Kobayashi, T.; Kanehiro, M.; Akazome, M.; Ogura, K.
Heterocycles 2010, 80, 645–656.
10. To a solution of compound 5 (8.0 g, 33.9 mmol) in EtOH (50 mL) and AcOH
(45 mL) containing concd H2SO4 (10 drops) was added 2-nitrophenylhydrazine
[stabilised with H2O (30%); 6.7 g, 30.1 mmol]. The mixture was stirred under
reflux (7 h), allowed to cool to room temperature and poured into H2O (ca.
200 mL). The mixture was extracted with CH2Cl2 (2 ꢁ ca. 50 mL) and the
combined organic layers washed with H2O (50 mL), dried (MgSO4) and
evaporated giving a maroon coloured solid (12.7 g). Recrystallisation from