1,2,4-Triazolo[1,2-a]benzotriazoles: First examples of a novel ring system

Article abstract of DOI:10.1016/S0040-4039(01)02023-8

α-Benzotriazolylamides 6a-d afforded N-(benzotriazol-1-ylmethyl)arylimidoyl chlorides (4a-d), which reacted in situ with potassium tert-butoxide to form 3-aryl-1,2,4-triazolo[1,2-a]benzotriazoles (7a-d) (44-68%), representatives of a novel heterocyclic system. The structure of 7a was confirmed by single crystal X-ray analysis.

Full text of DOI:10.1016/S0040-4039(01)02023-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 9109–9111
1,2,4-Triazolo[1,2-a]benzotriazoles: first examples of a
novel ring system
Alan R. Katritzky,a,* Tian-Bao Huanga,† and Peter J. Steelb,*
aCenter for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA
bDepartment of Chemistry, University of Canterbury, Christchurch, New Zealand
Received 20 September 2001; revised 18 October 2001; accepted 22 October 2001
Abstract—a-Benzotriazolylamides 6a–d afforded N-(benzotriazol-1-ylmethyl)arylimidoyl chlorides (4a–d), which reacted in situ
with potassium tert-butoxide to form 3-aryl-1,2,4-triazolo[1,2-a]benzotriazoles (7a–d) (44–68%), representatives of a novel
heterocyclic system. The structure of 7a was confirmed by single crystal X-ray analysis. © 2001 Elsevier Science Ltd. All rights
reserved.
1,2,4-Triazolo[1,2-a]benzotriazoles represent, to the
best of our knowledge, a previously unreported non-
classical tricyclic ring system. The few known bicyclic
1,2,4-triazolo[1,2-a]-1,2,3-triazoles (Scheme 1) were pre-
pared: (i) by cycloaddition of 4-phenyl-1,2,4-triazoline-
3,5-dione and vinyl azides to give A,1 and (ii) by
photoisomerization of 1,2,3-triazolo[1,2-b]-1,2,3-tria-
zoles to give B.2 We now disclose the first syntheses of
1,2,4-triazolo[1,2-a]benzotriazoles (7a–d).
pyrroles (1)3c or rearranges into 1,2,4-triazolo[1,5-
a]quinoxalines (5)3c (Scheme 2).
In further exploration of their synthetic utility, N-(ben-
zotriazol-1-ylmethyl)arylimidoyl chlorides (4a–d), (pre-
pared in situ from the corresponding a-benzotriazolyl
amides 6a–d,4a,b,c) were reacted with potassium tert-
butoxide. We now report that this gives 2-aryl-1,2,4-tri-
azolo[1,2-a]benzotriazoles 7a–d (44–68%) (Scheme 3).
N-(Benzotriazol-1-ylmethyl)arylimidates, 2 and 4, are
versatile synthetic building blocks: 2 cyclizes to give
pyrroles (1)3a,b and imidazoles (3),3b while 4 produces
The transformations of 4a–d into 7a–d (Scheme 3)
probably involve proton abstraction to furnish carban-
ion 9, which eliminates chloride to form nitrile ylide 10.
Intramolecular 8-electron electrocyclic rearrangement
of 10 gives 1,2,4-triazolo[1,2-a]benzotriazoles 7a–d.
Nitrile ylide species are known to be formed on addi-
tion of a carbene to acetonitriles5a or on photo-rear-
rangement of 2H-azirines.5b
O
R1
N
O
R1
N
N
N
N
N Ph
R
N Ph
R
N3
O
O
A
Structure 7a was confirmed by X-ray crystallography6
1
(Fig. 1) and is compatible with the H and 13C NMR
Ph
Ph
N
Ph
spectra.7 The structures of compounds 7b–d7 were
assigned by analogy and by spectroscopic data com-
parisons. Inspection of the bond lengths shown in Fig.
1, reveals that these compounds should not be repre-
sented by a single resonance contributor, and that there
is an important contribution from resonance structures
8a–d (Scheme 3). The crystal structure determination
shows that the 1,2,4-triazolo[1,2-a]benzotriazole ring
system is planar [average deviation from the plane=
N
hv
N
N
N
N
Ph
Ph
Ph
N
N
Ph
Ph
B
Scheme 1.
Keywords: benzotriazole; heterocyclic betaines; crystal structure.
* Corresponding authors. Fax: +1-352-392-9199; e-mail: katritzky
@chem.ufl.edu; p.steel@chem.canterbury.ac.nz
,
0.011 A]. Interestingly, the attached phenyl ring is
† Current address: Alchem Laboratories Corporation, 13305 Rachael
Blvd., Alachua, FL 32615, USA.
almost coplanar with the triazolobenzotriazole ring sys-
tem [angle between meanplanes=6.2°].
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02023-8

9110
A. R. Katritzky et al. / Tetrahedron Letters 42 (2001) 9109–9111
Ar
Ar
R
R
X
X
N
N
N
RCH=CHX
N
MeS
N
RCH=NX
base
Cl
N
PhCH2Cl
base
RCH=CHX
base
Ar
N
Ar
Ar
N
H
1
N
Bt
base
Bt
Ph
3
4
2
5
(Bt = benzotriazol-1-yl)
Scheme 2.
O
Bt
N
H
6a-d
Ar
90 oC
Cl
PCl5
For 4a-d
N
N
N
N
N
Ar
N
Ar
Bt
N
t-BuOK, 65 oC
N
N
Ar
4a-d
8
7
7a: Ar = C6H5-
7b: Ar = 4-Me-C6H4- 44%
7c: Ar = 2-Furyl- 68%
55%
- H+
t-BuOK
+H+
7d: Ar = 2-Br-C6H4- 51%
Cl
H
- Cl-
N
N
N
N
Ar
Ar
N
N
N:
N
9
10
Bt = benzotriazol-1-yl
Scheme 3.
The nature of the Ar substituent in the starting amide
(6) influences the reaction significantly: in 6c (Ar=2-
furyl), the isolated yield of 7c is 68%, compared with
44% for the para-tolyl derivative 7b.
In conclusion: we have disclosed the first synthesis of
3-aryl-1,2,4-triazolo[1,2-a]benzotriazoles (7a–d) via a
novel electrocyclic rearrangement in a one-pot protocol
utilizing readily available starting materials.
References
1. Hassner, A.; Tang, D.; Keogh, J. J. Org. Chem. 1976, 41,
2102–2104.
2. Kopecky, J.; Smejkal, J.; Turecek, F.; Jirkovsky, J.; Fojtik,
A.; Hanus, V. Tetrahedron Lett. 1984, 25, 2613–2616.
3. (a) Katritzky, A. R.; Huang, T.-B.; Voronkov, M. V.; Wang,
M.; Kolb, H. J. Org. Chem. 2000, 65, 8819–8821; (b)
Katritzky, A. R.; Zhu, L.; Lang, H.; Denisko, O.; Wang,
Z. Tetrahedron 1995, 51, 13271–13276; (c) Katritzky, A. R.;
Huang, T.-B.; Denisko, O.; Steel, P. J., unpublished work.
Figure 1. Perspective view and partial atom labeling of the
,
X-ray crystal structure of 7a. Selected bond distances (A):
N(1)ꢀC(2) 1.354(2); N(1)ꢀN(2) 1.381(2); N(1)ꢀC(3) 1.384(2);
N(2)ꢀN(3) 1.354(2); N(2)ꢀC(1) 1.354(2); N(3)ꢀC(4) 1.373(2);
N(4)ꢀC(2) 1.315(2); N(4)ꢀC(1) 1.356(2); C(1)ꢀC(9) 1.449(2);
C(3)ꢀC(4) 1.409(2).

A. R. Katritzky et al. / Tetrahedron Letters 42 (2001) 9109–9111
9111
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Trans. 1 1988, 2339–2344; (b) Katritzky, A. R.; Galuszka,
B.; Zhang, Y.; Rachwal, S. Org. Prep. Proced. Int. 1992,
24, 475–478; (c) Katritzky, A. R; Fang, Y.; Silina, A. J.
Org. Chem. 1999, 64, 7622–7624.
5. (a) Naito, I.; Nakamura, K.; Kumagai, T.; Oku, A.; Hori,
K.; Matsuda, K.; Iwamura, H. J. Phys. Chem. A 1999,
103, 8187–8192; (b) Albrecht, E.; Mattay, J.; Steenken, S.
J. Am. Chem. Soc. 1997, 119, 11605–11610.
zolo[1,2-a]benzotriazoles (7a–d) as yellow needles.
3-Phenyl-1,2,4-triazolo[1,2-a]benzotriazole (7a): yellow
needles (55%), mp 179–180°C; H NMR (CDCl3): l 6.99
1
(t, J=7.5 Hz, 1H), 7.32–7.42 (m, 2H), 7.48–7.59 (m, 3H),
7.65 (d, J=8.2 Hz, 1H), 8.36 (s, 1H), 8.47 (d, J=7.4 Hz,
2H); 13C NMR: l 110.6, 114.4, 116.9, 118.0, 118.2, 125.1,
126.7, 126.9, 127.9, 128.4, 128.9, 149.3. Anal. calcd for
C14H10N4: C, 71.78; H, 4.30; N, 23.92. Found: C, 71.86;
H, 4.30; N, 23.87. 3-(4-Methylphenyl)-1,2,4-triazolo[1,2-a]-
benzotriazole (7b): yellow needles (44%), mp 208–209°C;
1H NMR (CDCl3): l 2.42 (s, 3H), 7.03 (t, J=7.7 Hz, 1H),
7.34 (d, J=8.1 Hz, 2H), 7.43 (t, J=7.8 Hz, 1H), 7.60 (d,
J=7.8 Hz, 1H), 7.70 (d, J=8.1 Hz, 1H), 8.39 (d, J=8.4
Hz, 2H), 8.41 (s, 1H); 13C NMR: l 21.7, 110.7, 114.4,
117.0, 117.9, 118.2, 124.2, 125.2, 127.2, 128.0, 129.7, 138.6,
149.5. Anal. calcd for C15H12N4: C, 72.56; H, 4.87; N,
22.57. Found: C, 72.51; H, 5.00; N, 22.62. 3-(2-Furyl)-
1,2,4-triazolo[1,2-a]benzotriazole (7c): yellow needles
(68%), mp 212−213°C; 1H NMR (CDCl3): l 6.66 (dd,
J=3.3, 1.8 Hz, 1H), 7.10 (t, J=7.8 Hz, 1H), 7.31 (d,
J=3.3 Hz, 1H), 7.48 (t, J=8.1 Hz, 1H), 7.66–7.64 (m,
2H), 7.77 (d, J=8.1 Hz, 1H), 8.46 (s, 1H); 13C NMR: l
109.5, 110.9, 112.1, 114.8, 117.5, 118.3, 118.5, 120.6, 128.2,
142.1, 143.5, 149.6. Anal. calcd for C12H8N4O: C, 64.28;
H, 3.60; N, 25.00. Found: C, 64.54; H, 3.30; N, 25.04.
3-(2-Bromophenyl)-1,2,4-triazolo[1,2-a]benzotriazole (7d):
yellow needles (51%), mp 192–193°C; 1H NMR (CDCl3): l
7.11 (t, J=7.2 Hz, 1H), 7.32 (t, J=7.8 Hz, 1H), 7.46–7.55
(m, 2H), 7.62 (d, J=7.8 Hz, 1H), 7.80 (t, J=7.4 Hz, 2H),
8.24 (d, J=7.8 Hz, 1H), 8.57 (s, 1H); 13C NMR: l 110.9,
114.7, 117.4, 117.8, 118.4, 121.9, 125.1, 127.7, 127.8, 128.2,
130.6, 130.7, 134.6, 149.1. Anal. calcd for C14H9BrN4: C,
53.70; H, 2.90; N, 17.89. Found: C, 53.73; H, 2.85; N,
17.50.
6. Crystal Data for 7a: C14H10N4, Mw 234.26, orthorhombic,
space group Pca21, a=17.278(5), b=5.217(2), c=
3
,
,
12.286(4) A, V=1107.4(6) A , F(000)=488, Z=4, T=
−105°C, v (Mo Ka)=0.089 mm−1, Dcalcd=1.405 g cm−3
,
2qmax 50° (CCD area detector, Mo Ka radiation, 99.4%
completeness), GOF=1.039, wR(F2)=0.0675 (all 1934
data), R=0.0261 (1846 data with I>2|I).
7. Typical data for compounds 7a–d. General procedure for
the preparation of 3-aryl-1,2,4-triazolo[1,2-a]benzotria-
zoles (7a–d) from N-(benzotriazolylmethyl)arylamides (6a–
d): N-(benzotriazol-1-ylmethyl)arylcarboxamide4 (6a–d, 5
mmol) was dissolved in toluene (100 mL) and treated with
phosphorus pentachloride (1.25 g, 6 mmol). The reaction
mixture was heated at 90–100°C for 3 h, then it was
filtered while hot, and the solvent and POCl3 were
removed under reduced pressure. The crude imidoyl chlo-
ride (4a–d) obtained was used in the subsequent reaction
without additional purification. A mixture of crude imi-
doyl chloride (4a–d, 0.83 g, 3 mmol) in dry tetra-
hydrofuran (30 mL) was treated with potassium
tert-butoxide (1.12 g, 10 mmol). The reaction mixture was
stirred for 0.5 h at room temperature, heated under reflux
for an additional 6 h, allowed to cool down and filtered.
The residue obtained after solvent evaporation was
purified by column chromatography (eluting with hexane/
EtOAc=6/1) to give the corresponding 3-aryl-1,2,4-tria-