Synthesis of tetrazolo[1,5-C]quinazolines VIA Ph3PAuOTf- catalyzed double hydroamination of terminal alkynes

Article abstract of DOI:10.14233/ajchem.2014.16157

An efficient tandem process is developed by using Ph₃PAuOTf- catalyzed double hydroamination of alkynes for the synthesis of new fused tetrazolo[1,5-c]quinazolines, with 2-(1 H-tetrazol-5-yl)anilines and alkynes in DCE at 100 °C.

Full text of DOI:10.14233/ajchem.2014.16157

Asian Journal of Chemistry; Vol. 26, No. 10 (2014), 2971-2973
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.16157
Synthesis of Tetrazolo[1,5-c]quinazolines via Ph3PAuOTf-Catalyzed
Double Hydroamination of Terminal Alkynes
*
PEDIREDLA G.V.V. LAKSHMI and NITIN T. PATIL
Division of Crop Protection Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, India
*Corresponding author: E-mail: p.g.v.v.lakshmi@gmail.com
Received: 7 August 2013;
Accepted: 26 November 2013;
Published online: 10 May 2014;
AJC-15160
An efficient tandem process is developed by using Ph3PAuOTf-catalyzed double hydroamination of alkynes for the synthesis of new
fused tetrazolo[1,5-c]quinazolines, with 2-(1H-tetrazol-5-yl)anilines and alkynes in DCE at 100 °C.
Keywords: Ph3PAuOTf, 2-(1H-Tetrazol-5-yl)anilines, Alkynes, Tetrazolo[1,5-c]quinazolines, Double hydroamination.
6.95 (m, 2H), 5.40 (bs, 1H), 2.38 (s, 3H); 13C NMR (CDCl3,
75 MHz): δ 149, 141.4, 133.3, 128.7, 125.8, 124.9, 120.8,
INTRODUCTION
116.1, 109.1, 76.9, 28.7; IR (KBr, νmax, cm-1): 3369, 3205,
3080, 2861, 1693, 1645, 1612, 1500, 1468, 1453, 992, 910;
Metal catalyzed tandem reactions for the addition of
nucleophiles to unactivated alkynes is one of the simplest and
atom economical1 synthetic transformation for the synthesis
HRMS Calcd. for C15H14N5 (M+ · + H) 264.1249, found
of various poly heterocyclic compounds2.Among all transition
264.1245.
metals3 shown significant activity for the addition of N-H bonds
across unactivated C-C triple bonds4.
Metal-catalyzed double addition of nucleophiles to alkynes
RESULTS AND DISCUSSION
Firstly 2-(1H-tetrazol-5-yl)aniline7 (1a) when treated with
ethynylbenzene (2a) in the presence of different metal catalysts
is playing a prominent role in the synthesis of privileged complex
compounds5. In this regard we developed double hydro-
and with various solvents, finally found that the best condition
amination of terminal alkynes6 by using tetrazole substituted
for the formation of expected product 5-methyl-5-phenyl-5,6-
dihydrotetrazolo[1,5-c]quinazoline (3a) in 85 % yield was in
the presence of 2 mol % Ph3PAuOTf catalyst in DCE at 100 °C
anilines as nucleophiles for the formation of new fused
tetrazole quinazolines.
for 24 h was optimal. Likewise, treated 1a with other alkynes
oct-1-yne (2b) and but-3-ynylbenzene (2c) gave the expected
products 3b and 3c in 78 and 79 % yield, respectively. Next to
check the generality methyl substituted 1a i.e., 1b8 reacted
well with the alkynes 2a, 2b and 2c afforded 3d, 3e and 3f in
81, 83 and 72 % yield, respectively. Finally, 4-methoxy-2-(1H-
tetrazol-5-yl)aniline8 (1c) was used as the substrate to react
with the alkynes 2a, 2b and 2c gave the corresponding products
3g, 3h and 3i in increasing yield, 89, 80 and 82 % respectively
(Table-1).
EXPERIMENTAL
General method for the synthesis of fused tetrazoloqui-
nazolines: To a screw cap vial containing a stir bar, were added
2-(1H-tetrazol-5-yl)aniline (1) (0.621 mmol), alkyne 2 (0.745
mmol) and 2 mol % Ph3PAuOTf (Ph3PAuCl/AgOTf) in DCE
(2 mL). The reaction vial was evacuated and filled with nitrogen
and heated at 100 °C for 24 h. The reaction mixture was cooled
to room temperature, diluted with ethyl acetate and filtered
through a plug of silica gel. The filtrate was concentrated and
the residue was purified by silica gel column chromatography
using hexane/ethyl acetate (90/10) as an eluent to afford analy-
tically pure compound 3.
Conclusion
We have developed Ph3PAuOTf-catalyzed direct double
hydroamination of alkynes for the synthesis of new fused
tetrazolo[1,5-c]quinazolines from 2-(1H-tetrazol-5-yl)anilines
and alkynes in the presence of 2 mol % Ph3PAuOTf catalyst in
DCE at 100 °C for 24 h.
5-Methyl-5-phenyl-5,6-dihydrotetrazolo[1,5-c]quina-
zoline (3a): 85 % yield; light yellow solid; m.p. = 170-172 °C;
1
Rf = 0.31 (hexane/EtOAc = 70/30); H NMR (CDCl3, 300
MHz): δ 7.93 (d, J = 6.9 Hz, 1H), 7.40-7.27 (m, 6H), 7.04-

2972 Lakshmi et al.
Asian J. Chem.

Vol. 26, No. 10 (2014)
Synthesis of Tetrazolo[1,5-c]quinazolines via Ph3PAuOTf-Catalyzed 2973
Int. Ed., 40, 3983 (2001); (f) T.E. Müller and M. Beller, Chem. Rev.,
98, 675 (1998); (g) For selected recent examples, see: H. Duan, S.
Sengupta, J.L. Petersen, N.G. Akhmedov and X. Shi, J. Am. Chem.
Soc., 131, 12100 (2009); (h) X.-Y. Liu and C.-M. Che, Org. Lett., 11,
4204 (2009); (i) X. Zeng, G.D. Frey, S. Kousar and G. Bertrand, Eur. J.
Chem., 15, 3056 (2009); (j) S.R. Beeren, S.L. Dabb and B.A. Messerle,
J. Organomet. Chem., 694, 309 (2009); (k) J.M. Carney, P.J. Donoghue,
W.M. Wuest, O. Wiest and P. Helquist, Org. Lett., 10, 3903 (2008).
4. N.T. Patil, R.D. Kavthe and V.S. Shinde, Tetrahedron, 68, 8079 (2012).
5. N.T. Patil, P.G.V.V. Lakshmi, B. Sridhar, S. Patra, M. Pal Bhadra and
C.R. Patra, Eur. J. Org. Chem., 1790 (2012).
ACKNOWLEDGEMENTS
One of the authors PGVVL acknowledge the CSIR for
financial support.
REFERENCES
1. (a) For reviews on atom economy, see: R.A. Sheldon, Pure Appl. Chem.,
72, 1233 (2000); (b) B.M. Trost, Science, 254, 1471 (1991); (c) B.M.
Trost, Angew. Chem. Int. Ed. Engl., 34, 259 (1995).
2. N.T. Patil, V.S. Shinde and B. Sridhar, Angew. Chem. Int. Ed., 52, 2251
(2013).
6. N.T. Patil, P.G.V.V. Lakshmi and V. Singh, Eur. J. Org. Chem., 4719
(2010).
3. (a) T.E. Müller, K.C. Hultzsch, M. Yus, F. Foubelo and M. Tada, Chem.
Rev., 108, 3795 (2008); (b) R. Severin and S. Doye, Chem. Soc. Rev.,
36, 1407 (2007); (c) F. Pohlki and S. Doye, Chem. Soc. Rev., 32, 104
(2003); (d) F. Alonso, I.P. Beletskaya and M. Yus, Chem. Rev., 104,
3079 (2004); (e) M. Nobis and B. Drießen-Hölscher, Angew. Chem.
7. L. Lang, B. Li, W. Liu, L. Jiang, Z. Xu and G. Yin, Chem. Commun.,
46, 448 (2009).
8. B.V. Golomolzin and I.Y. Postovskii, Chem. Heterocycl. Compd., 6,
266 (1970).