A facile, mild and efficient one-pot synthesis of 2-substituted indole derivatives catalyzed by Pd(PPh3)2Cl2

Article abstract of DOI:10.3390/12071438

2-Phenylindoles were prepared by heteroannulation of 2-haloaniline derivatives and phenylacetylene under mild conditions in a one-pot reaction catalyzed by Pd(PPh₃)₂Cl₂.

Full text of DOI:10.3390/12071438

Molecules 2007, 12, 1438-1446
molecules
ISSN 1420-3049
2007 by MDPI
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Communication
A Facile, Mild And Efficient One-Pot Synthesis of 2-Substituted
Indole Derivatives Catalyzed By Pd(PPh ) Cl
3
2
2
Hossien A. Oskooie*, Majid M. Heravi* and Farahnaz K. Behbahani
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
*
Authors to whom correspondence should be addressed; E-mails: majid1313@yahoo.com;
mmh1331@yahoo.com
Received: 8 March 2007; in revised form: 1 July 2007 / Accepted: 2 July 2007 / Published: 19 July
007
2
Abstract: 2-Phenylindoles were prepared by heteroannulation of 2-haloaniline derivatives
and phenylacetylene under mild conditions in a one-pot reaction catalyzed by
Pd(PPh
3 2 2
) Cl .
Key words: One-pot synthesis, 2-phenylindole, palladium catalyst, heteroannulation.
Introduction
The indole ring system is found in many natural products, pharmaceutical agents and polymer
materials [1]. The interesting chemical properties of indole have inspired chemists to design and
synthesize a variety of indole derivatives [2]. The 2-aryl indole moiety is present in diverse
biologically active molecules [3] displaying antiestrogen [3b,d] 5-H-T2A antagonist [3f], anti-
inflammatory [3a,c] and cytoxic properties [3e]. Introduction of an aryl group into the 2- or 3-position
of an indole ring is usually achieved either by de novo indole ring construction [2], as in the Fischer
indole synthesis [3a], or via cross-coupling reactions of 2- or 3-indolylmetal species with an aryl
halide [4] and related syntheses. These are the most commonly used routes and have been extensively
reviewed [5]. Although many synthetic methods have been developed for indoles, palladium-mediated
indole synthesis is one of the most active research fields [6]. Specifically, the palladium-catalyzed
annulation of o-haloanilines with alkynes has received much attention, as it is a very convenient way

Molecules 2007, 12
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439
to synthesize 2- or 2,3-substituted indoles [7,8]. The Sonogashira cross-coupling reaction of halo
anilines with terminal alkynes in the presence of Pd(0)-Cu(I) gives 2-alkynylanilines and the resulting
coupled products have been cyclized to give 2-substituted indoles using various metal alkoxides [8f,9]
and Lewis acids [10]. The annulation method is an effective way to prepare a variety of heterocycles
[
11]. We have recently reported the synthesis of various heterocyclic compounds [12] using Pd
catalyzed reactions and in this communication we wish to now report the extension of our strategy to
the synthesis of 2-phenylindoles.
Results and Discussion
In this reaction, we used a mixture of the aryl halide (0.075 mmol), phenylacetylene (1.5 mmol),
Pd(PPh ) Cl (0.025 mmol), CuI (0.055 mmol) and triethylamine (2 mmol) in DMF (5 mL) at ambient
3
2
2
temperature. The reaction provided 2-phenylindole as the major product. Next, we investigated the
reaction of N-acetyl-2-iodoaniline with phenylacetylene as a model to study the intermolecular
heteroannulation with the Pd(PPh ) Cl catalyst. This reaction also gave 2-phenylindole as the major
3
2
2
product, instead of the expected N-acetyl-2-phenylindole. The deprotection of the acetyl group in the
indole likely occurred as a result of the basic conditions of the reaction. N-methyl, N-benzyl and N-
tosyl 2-haloanilines effectively reacted with phenylacetylene and the corresponding 2-phenylindole
derivatives were obtained in good yields (Scheme 1, Table 1).
Scheme 1.
X
Ph
Ph
Ph
or
NHR
NH
(
PPh ) PdCl
NR
3
2
2
DMF, Et N, CuI
3
X=Br, I
R= H, Ac, Me, Bn, Ts
Table 1. Synthesis of 2-substituted indoles by Pd-catalyzed heteroannulation with phenylacetylene.
Entry
Aryl halide
Product
Yield%
I
1
72
N
H
NH2
I
2
3
4
69
78
75
NHAc
Br
″
″
″
NH2
Br
NHAc

Molecules 2007, 12
1
440
Table 1. Cont.
Entry
Aryl halide
Product
Yield%
Br
5
N
82
NHMe
I
6
7
8
″
NHMe
80
74
Br
N
NHBn
I
76
68
″
NHBn
N
Br
SO2
9
NHTs
I
1
0
″
70
68
NHTs
I
NH
1
1
NH2
When we tried to use tetrahydropyranyl propargyl ether or propargyl bromide instead of
phenylacetylene, these reactions did not give any products. We also tried to use 1-heptyne instead of
phenylacetylene, but the reaction did not give any of the desired 2-alkylindole derivative under our
standard mild conditions. We then examined this reaction under more forcing conditions. After 24 hrs
at reflux the reaction went to completion and 2-pentyl-1H-indole was obtained in 68% yield.
Scheme 2.
Ph
X
Sonogashira coupling
Ph
Pd(II)
+
Ph
NH2
DMF, Et N, CuI
NH2
3
NH
(
PPh ) PdCl
3 2 2
The mechanism of the reaction is illustrated in Scheme 2. Most probably a two step process occurs:
first a standard Sonogashira coupling and then the known Pd (II) catalyzed intermolecular cyclization
of the nucleophilic nitrogen moiety onto the triple bond, followed by proton abstraction.

Molecules 2007, 12
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441
Conclusions
In summary, we have demonstrated that indoles can be synthesized from anilines and phenyl-
acetylene in the presence of a palladium catalyst in an organic medium in moderate to good yields.
3 2 2
Pd(PPh ) Cl exhibits high reactivity in the heteroannulation of o-haloanilines and phenylacetylene.
This method provides a convenient new route to various heteroannulation products in a one-pot
reaction. We believe this process combined with an amine exchange reaction can be successfully
applied for the synthesis of other N-heterocycles. We also consider the preparation of Pd(PPh
3 2 2
) Cl
(
this work) to be more economical and simpler than other recently published procedures (for example,
Pd-NaY Zeolite [13]).
Experimental
General
All products are known and their physical and spectroscopic data were compared with the reported
values. GC–MS analyses were performed on an Agilent system consisting of a GC–MS model 5973
network mass selective detector and a model 6890 GC. IR spectra were obtained with a Buck
1
Scientific model 500 spectrometer. H-NMR spectra were recorded on a Bruker 90 MHz FT-NMR .
3 2 2
Preparation of Pd(PPh ) Cl
Following the general procedure of Heck [15], to a solution of palladium (II) chloride (0.05 mol,
.85 g) and LiCl (0.1 mol, 4.25 g) in dry methanol (80 mL) was added triphenylphosphine (0.11 mol,
7.5 g). The resulting reddish brown reaction mixture was heated in a water bath (temp. 80 °C) until a
8
2
yellow and nearly insoluble solid formed. The reaction mixture was cooled to ambient temperature and
the yellow product (32.7 g, 93%) collected by vacuum filtration washed with methanol (25 mL) and
dried overnight in a desiccator prior to use.
3 2 2
General procedure for the synthesis of 2-substituted-1H-indoles with Pd(PPh ) Cl
A mixture of the appropriate 2-arylhalide (0.75 mmol), Pd(PPh
3 2 2
) Cl (0.0175 g, 0.025 mmol), CuI
(0.01 g, 0.055 mmol), triethylamine (0.202 g, 0.278 mL, 2 mmol) and phenylacetylene (0.153 g, 1.5
mmol) were stirred in DMF (5 mL) at room temperature for 24 h. Upon completion of the reaction, the
reaction mixture was diluted with saturated aqueous ammonium chloride and the product was
extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The
reaction mixture was filtered and concentrated. The product was purified by silica gel column
chromatography using hexane/ethyl acetate as eluent. The 2-phenyl-1H-indole was obtained in 69-
1
7
8% yields (Table 1, entries 1-4). Mp 189–190 °C; H-NMR (CDCl
.42–7.27 (m, 4H), 7.20–7.09 (m, 2H), 6.80 (s, 1H).
3
) 8.34 (s, br, 1H), 7.62 (m, 3H),
7

Molecules 2007, 12
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442
Synthesis of 1-methyl-2-phenylindole; (Table 1, entries 5, 6)
N-Methyl-2-bromo(iodo)aniline [15] [0.139 (0.175) g, 0.75 mmol], Pd(PPh ) Cl (0.0175 g, 0.025
3 2 2
mmol), CuI (0.01 g, 0.055 mmol), triethylamine (0.202 g, 0.278 mL, 2 mmol), phenylacetylene (0.153
g, 1.5 mmol) and DMF (5 mL) were mixed at room temperature for 8 h. The progress of the reaction
was monitored by TLC. Upon completion of the reaction the mixture was diluted with saturated
aqueous ammonium chloride and the product was extracted with ethyl acetate. The organic layer was
dried over MgSO
4
and filtered. The crude product was purified by silica gel column chromatography
1
using hexane/ethyl acetate to afford 1-methyl-2-phenyl indole as a brown solid. Mp. 110-112°C; H-
NMR (CDCl
Synthesis of 1-benzyl-2-phenylindole (Table 1, entries 7, 8)
Pd(PPh Cl (0.0175 g, 0.025 mmol), N-benzyl-2-bromo(iodo)aniline [15] [0.197 (0.232) g, 0.75
3
) 7.38 (m, 2H), 7.32 (m, 2H), 7.22 (m, 1H), 7.2 (m, 4H), 6.5 (s, 1H), 3.56 (s, 3H).
3
)
2
2
mmol], CuI (0.01 g, 0.055 mmol), triethylamine (0.202 g, 0.278 mL, 2 mmol), phenylacetylene (0.153
g, 1.5 mmol) and DMF (5 mL) were placed in a sealed tube at room temperature for 12 h. Upon
completion of reaction, the reaction mixture was worked up and purified as described above. 1-Benzyl-
1
2
-phenylindole was obtained in 74 (76%) yield. Mp. 95-99°C; H-NMR (CDCl
.4 (s, 1H), 5.1 (s, 2H).
3
) 7.6-7.07 (m, 14H),
6
Synthesis of 2-phenyl-1-(toluene-4- sulfonyl)indole (Table 1, entries 9, 10)
Pd(PPh Cl (0.0175 g, 0.025 mmol), N-tosyl-2-bromo(iodo)aniline [16] [0.222 (0.257) g, 0.75
3
)
2
2
mmol], CuI (0.01 g, 0.055 mmol), triethylamine (0.202 g, 0.278 mL, 2 mmol), phenylacetylene (0.153
g, 1.5 mmol) and DMF (5 mL) were placed in a sealed tube at room temperature for 12 h. As above, 2-
1
phenyl-1-(toluene-4-sulfonyl)indole was obtained in 68 (70)% yield. Brown solid; Mp. 75-99°C; H-
NMR (CDCl
Synthesis of 2-pentyl-1H-indole (Table 1, entry 11)
Pd(PPh Cl (0.0175 g, 0.025 mmol), 2-iodoaniline (0.164 g, 0.75 mmol), CuI (0.01g, 0.055
3
) 7.81-7.0 (m, 13H), 6.4 (s, 1H), 2.35 (s, 2H).
3
)
2
2
mmol), triethylamine (0.202 g, 0.278 mL, 2 mmol), 1-heptyne (0.144 g, 1.5 mmol) and DMF (5 mL)
were heated under reflux conditions for 24 h. After workup as described above, 2-pentyl-1H-indole
1
was obtained in 68 % yield. Brown oil; H-NMR (CDCl
3
) 7.81-7.0 (m, 4H), 6.4 (s, 1H), 2.65 (t, 2H),
1.6-1.45(m, 6H), 1.05(t, 3H).
Acknowledgments
The authors are thankful for the partial financial assistance from Azzahra University Research
Council.

Molecules 2007, 12
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References and Notes
1
.
Gribble, G.W. Pyrroles and benzo derivatives: applications; In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., (Eds.); Pergamon Press: New
York, Oxford, 1996; Vol. 2, pp. 207-256, and references cited therein.
2
.
.
Gribble, G. W. Recent developments in indole ring synthesis-methodology and applications. J.
Chem. Soc. Perkin Trans. 1 2000, 1045-1047.
3
a) Von Angerer, E.; Knebel, N.; Kager, M.; Ganss, B. 1-(Aminoalkyl)-2-Phenylindoles As Novel
Pure Estrogen Antagonists. J. Med. Chem. 1990, 33, 2635-2640; b) Ismail, M. F.; Shmeiss, N. A.
M. M.; El-Diwani, H. I.; Arbid, M. S. Synthesis and pharmacological activity of some 2,3-
diphenylindole derivatives. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1997, 36B,
288-292; c) Biberger, C.; Von Angerer, E.1-benzyl-2-phenylindole- and 1,2-diphenylindole-
based antiestrogens. Estimation of agonist and antagonist activities in transfection assays. J.
Steroid Biochem. Mol. Biol. 1998, 64, 277-281; d) Medarde, M.; Ramos, A. C.; Caballero, E.; De
Clairac, R. P. L.; Lopez, J. L.; Gravalos, D. G.; Feliciano, A. S. Synthesis and inotropic activity
of hydroindene derivatives. Bioorg. Med. Chem. Lett. 1999, 9, 2303-2308; e) Stevenson, G. I.;
Smith, A. L.; Lewis, S.; Michie, S. G. ; Neduvelil, J. G.; Patel, S.; Marwood, R.; Castro, J. L.
Solid-phase synthesis of 2,3-disubstituted indoles: Discovery of a novel, high-affinity, selective
h5-HT2A antagonist. Bioorg. Med. Chem. Lett. 2000, 10, 2697-2699; f) Colletti, S. L.; Li, C.;
Fisher, M. H.; Wyvratt, M. J.; Meinke, P. T. Tryptophan-replacement and indole-modifed
apicidins: synthesis of potent and selective antiprotozoal agents. Tetrahedron Lett. 2000, 41,
7825-7827.
4
. a) Newcastle, G. W Katritzky, A. R. Generation And Reactions Of Sp(2)-Carbanionic Centers In
The Vicinity Of Heterocyclic Nitrogen-Atoms. Adv. Heterocycl. Chem. 1993, 56, 155; b)
Hudkins, R. L.; Diebold, J. L.; Marsh, F. D. Synthesis Of 2-Aryl-1H-Indoles And 2-Vinyl-1H-
Indoles Via Palladium-Catalyzed Cross-Coupling Of Aryl And Vinyl Halides With 1-Carboxy-
2
-(Tributylstannyl)Indole. J. Org. Chem. 1995, 60, 6218-6220; c) Amat, M. Hadida, S.;
Pshenichnyi, G.; Bosch, J. Palladium(0)-catalyzed heteroarylation of 2- and 3-indolylzinc
derivatives. An efficient general method for the preparation of (2-pyridyl)indoles and their
application to indole alkaloid synthesis. J. Org. Chem. 1997, 62, 3158-3162; d) Kawasaki, I.;
Yamashita, M.; Ohta, S. Total synthesis of nortopsentins A-D, marine alkaloids. Chem. Pharm.
Bull. 1996, 44, 1831-1837; e) Johnson, C. N.; Stemp, G.; Anand, N.; Stephen, S. C.; Gallagher,
T. Palladium (0)-catalysed arylations using pyrrole and indole 2-boronic acids. Synlett 1998,
1025-1027.
5.
a) Sundberg, R. J. Pyrroles and benzo derivatives: synthesis; In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., (Eds.); Pergamon Press: New
York, Oxford, 1996; vol. 2, pp. 119-206; b) Sundberg, R. J.; Indoles; Academic Press: London,
1
996.
6.
a) Li, J. J.; Gribble, G. W. Palladium in Heterocyclic Chemistry; Pergamon: Amsterdam, 2000;
b) Suzuki, N.; Yasaki, S.; Yasuhara, A.; Sakamoto, T. Convenient indole synthesis from
2
-iodoanilines and terminal alkynes by the sequential Sonogashira reaction and the cyclization
reaction promoted by tetrabutylammonium fluoride (TBAF). Chem. Pharm. Bull. 2003, 51,

Molecules 2007, 12
170-1173; c) Yasuhara, M. C.; Kanamori, Y.; Kaeko, M.; Numata, A.; Kondo, Y.; Sakamoto,T.
1
444
1
Convenient synthesis of 2-substituted indoles from 2-ethynylanilines with tetrabutylammonium
fluoride J. Chem. Soc., Perkin Trans. 1 1999, 529-534; c) Falco, J. L.; Pique, M.; Gonzalez, M.;
Buira, I.; Mendez, E.; Terencio, J.; Perez, C.; Princep, M.; Palomer, A.; Guglietta, A. Synthesis,
pharmacology and molecular modeling of N-substituted 2-phenyl-indoles and benzimidazoles as
potent GABA(A) agonists. Eur. J. Med. Chem. 2006, 41, 985-990; d) Feuerstein, M.; Doucet,
H.; Santelli, M. Sonogashira reaction of heteroaryl halides with alkynes catalysed by a
palladium-tetraphosphine complex. J. Mol. Catal. A: Chem. 2006, 256, 75-84; e) Lu, B. Z.;
Zhao, W.Y.; Wei, H. X.; Dufour, M.; Farina, V.; Senanayake, C. H. A practical mild, one-pot,
regiospecific synthesis of 2,3-disubstituted indoles via consecutive Sonogashira and Cacchi
reactions. Org. Lett. 2006, 8, 3271-3274; f) Tang, Z. Y.; Hu, Q. S. Efficient synthesis of 2-
substituted indoles based on palladium(II) acetate/tri-tert-butylphosphine-catalyzed alkynylation/
amination of 1,2-dihalobenzenes. Adv. Synth. Catal. 2006, 348, 846-850; h) Yue, D. W.; Yao, T.
L.; Larock, R. C. Synthesis of 3-iodoindoles by the Pd/Cu-catalyzed coupling of N,N-dialkyl-2-
iodoanilines and terminal acetylenes, followed by electrophilic cyclization. J. Org. Chem. 2006,
7
1, 62-69; i) Pal, M.; Subramanian, V.; Batchu, V. R.; Dager, I. Synthesis of 2-substituted
indoles via Pd/C-catalyzed reaction in water. Synlett 2004, 1965-1969.
7.
a) Arcadi, A.; Cacchi, S. Marinelli, F. A Versatile Approach To 2,3-Disubstituted Indoles
Through The Palladium-Catalyzed Cyclization Of Ortho-Alkynyltrifluoroacetanilides With
Vinyl Triflates And Aryl Halides. Tetrahedron Lett. 1992, 33, 3915-3917; b) Zhang, H. C.; Ye,
H.; Moretto, A. F.; Brumfield, K. K.; Maryanoff, B. E. Facile solid-phase construction of indole
derivatives based on a traceless, activating sulfonyl linker. Org. Lett. 2000, 2, 89-90; c) M. C.
Fagnola, I. Candiani, G. Visentin, W. Cabri, F. Zarini, N. Mongelli, A. Bedeschi, Solid-phase
synthesis of indoles using the palladium-catalysed coupling of alkynes with iodoaniline
derivatives. Tetrahedron Lett. 1997, 38, 2307-2309; d) Zhang, H. C.; Ye, H.; White, K. B.;
Maryanoff, B. E. Efficient synthesis of 3-substituted 2-arylindoles via Suzuki coupling reactions
on the solid phase Tetrahedron Lett. 2001, 42, 4751-4753; e) Dai, W. M.; Guo, D. S.; Sun, L. P.
Chemistry of aminophenols. Part 1: Remarkable additive effect on Sonogashira cross-coupling
of 2-carboxamidoaryl triflates and application to novel synthesis of indoles. Tetrahedron Lett.
2
001, 42, 5275-5277; f) Dai, W. M.; Sun, L. P.; Guo, D. S. Chemistry of aminophenols. Part 2:
A general and efficient synthesis of indoles possessing a nitrogen substituent at the C4, C5, C6,
and C7 positions. Tetrahedron Lett. 2002, 43, 7699-7701.
8.
a) Larock, R. C.; Yum, E. K. Synthesis Of Indoles Via Palladium-Catalyzed Heteroannulation
Of Internal Alkynes J. Am. Chem. Soc. 1991,113, 6689-6690; b) Larock, R. C.; Yum, E. K.;
Refvik, M. D.; Synthesis of 2,3-disubstituted indoles via palladium-catalyzed annulation of
internal alkynes. J. Org. Chem. 1998, 63, 7652-7662; c) Roesch, K. R.; Larock, R. C. Synthesis
of isoindolo[2,1-a]indoles by the palladium-catalyzed annulation of internal alkynes. Org. Lett.
1
999, 1, 1551-1553; d) Jeschke, T.; Wensbo, D.; Annby, U.; Gronowitz, S. A Novel-Approach
To Bz-Substituted Tryptophans Via Pd-Catalyzed Coupling Annulation. Tetrahedron Lett. 1993,
4,6471-4673; e) Chen, C. Y.; Lieberman D. R.; Larsen, R. D.; Reamer, R. A.; Verhoven, T. R.;
Reider, P. J.; Cottrell, I. F.; Houghton, P. G.; Synthesis Of The 5-Ht1d Receptor Agonist Mk-
462 Via A Pd-Catalyzed Coupling Reaction Tetrahedron Lett. 1994, 35, 6981-6983; f) Zhang,
3
0

Molecules 2007, 12
1
445
H.-C. Brumfield, K. K.; Maryanoff, B. E. Synthesis of trisubstituted indoles on the solid phase
via palladium-mediated heteroannulation of internal alkynes Tetrahedron Lett. 1997, 38, 2439-
2441.
9.
a) Kondo, Y. Kojima, S. Sakamoto, T. General and facile synthesis of indoles with oxygen-
bearing substituents at the benzene moiety. J. Org. Chem. 1997, 62, 6507-6513; b) Rodriguez, A.
L.; Koradin, C.; Dohle, W.; Konchel, P. Versatile indole synthesis by a 5-endo-dig cyclization
mediated by potassium or cesium bases. Angew. Chem. Int. Ed. 2000, 39, 2488-2494.
1
0. a) Saulnier, M. G.; Fennesson, D. B.; Deshpande, M. S.; Vyas, D. M. Synthesis Of A
Rebeccamycin-Related Indolo[2,3-A]Carbazole By Palladium(0) Catalyzed Polyannulation.
Tetrahedron Lett. 1995, 36, 7841-7843; b) Hiroya, K.; Itoh, S.; Ozawa, M.; Kanamori, Y.;
Sakamoto, T. Efficient construction of indole rings from 2-ethynylaniline derivatives catalyzed
by copper(II) salts and its application to the tandem cyclization reactions. Tetrahedron Lett.
2
002, 43, 1277-1279; c) Roshchin, A. I.; Bumagin, N. A. Synthesis of 2-phenylindole N-
derivatives under conditions of catalysis by palladium complexes. Khim. Geterotsikl. Soedin.
999, 2, 194-198 (in Russian); d) Sakai, N.; Annaka, K.; Konakahara, T. Palladium-Catalyzed
1
Coupling Reaction of Terminal Alkynes with Aryl Iodides in the Presence of Indium Tribromide
and Its Application to a One-Pot Synthesis of 2-Phenylindole Org. Lett. 2004, 4, 1527-1530.
1. a) Larock, R. C. Palladium-catalyzed annulation. J. Organomet. Chem. 1999, 576,111-1124; b)
Larock, R. C.; Palladium-catalyzed annulation. Pure Appl. Chem. 1999, 71, 1435-1442.
1
1
2. a) Heravi, M. M.; Bakavoli, M. Synthesis of a novel heterocyclic system, thiazolo[3,2-
d][1,2,4]triazine. J. Chem. Res. 1995, 480-481; b) Heravi, M. M.; Aghapoor, K.; Nooshabadi, M.
A.; Mojtahedi, M. G. Regioselective annelation of 3-(prop-2-ynylsulfanyl)-1,2,4-benzotriazine to
thiazolo[2,3-c][1,2,4]benzotriazine. Monatsh. Chem., 1997, 128,1143-1146; c) Heravi, M. M.;
Keivanloo, A.; Rahimizadeh, M.; Bakavoli, M.; Ghassemzadeh, M. Heteroannulation through
palladium catalysis: A novel cyclization leading to regioselective synthesis of 3-substituted
thiazolo[3,2-C]1,2,4-triazin-5-ones. Phosphorus, Sulfur Silicon Relat. Elem. 2002, 177, 2491-
2496; d) Heravi, M. M.; Keivanloo, A.; Rahimizadeh, M.; Bakavoli, M.; Ghassemzadeh, M. Pd-
Cu catalyzed heterocyclization during Sonogashira coupling: synthesis of 3-benzylthiazolo[3,2-
a]benzimidazole. Tetrahedron Lett. 2004, 45, 5747-5749; e) Heravi, M. M.; Keivanloo, A.;
Rahimizadeh, M.; Bakavoli, M.; Ghassemzadeh, M.; Regioselective synthesis of 6-
benzylthiazolo[3,2-b]1,2,4-triazoles during Sonogashira coupling. Tetrahedron Lett. 2005, 46,
1607-1610.
13. Hong, K. B.; Lee, W. C.;Yum, E. K. Synthesis of 2-substituted indoles by palladium-catalyzed
heteroannulation with Pd-NaY zeolite catalysts. Tetrahedron Lett. 2004, 45, 693-694.
1
4. a) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic Press: London, 1985; b)
Chen, M.-Y.; Fang, J.-M. J. Chin. Chem. Soc. 1989, 36, 469-472; c) Bernstein, R. B. Chemical
Dynamics via Molecular Beam and Laser Techniques; Oxford: New York, 1982; Chapter 9; d)
Talley, L. D.; Lin, M. C. In Aspects of the Kinetics and Dynamics of Surface Reactions;
Landman, U., Ed.; AIP Conf. Proceed., American Institute of Physics: New York, 1980, pp. 297-
306; e) Huang, C.-M. M. S. Thesis, Fu Jen Catholic University, Taiwan, 1987.

Molecules 2007, 12
1
446
15. Moore, J. L.; Stephen M. Taylor, S. M.; Soloshonok, V. A. An efficient and operationally
convenient general synthesis of tertiary amines by direct alkylation of secondary amines with
alkyl halides in the presence of Huenig’s base. Arkivoc 2005, (vi), 287-292.
6. Shriner, R. L.; Fuson, R. C.; Curtin, D. Y.; Morrill, T. S. Systematic Identification of Organic
Compounds, 6th edn.: Wiley: New York, 1980.
1
Sample Availability: Available from the authors.
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