Palladium-copper catalyzed synthesis of benzofused heterocycles with two heteroatoms: Novel and highly regio- and stereoselective syntheses of (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles and (E)-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzothiazines

Article abstract of DOI:10.1021/jo001783+

A highly novel, general, and convenient palladium and copper-catalyzed procedure has been developed for the synthesis of (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles 28-40. 3-(2-Aminophenylthio)prop-1-yne 1 reacts with aryl iodides 2-14 under palladium-copper catalysis to yield the disubstituted alkynes 15-27 which after tosylation undergo a novel cyclization with CuI in the presence of triethylamine in THF to (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles 28-40 rather than to the expected 3-alkylidene-4-tosyl-3,4-dihydro-2H-1,4-benzothiazines 41. The reaction is highly regio- and stereoselective. The synthesis of 2-(2-arylethyl)-3-tosylbenzothiazolines 42-47, 2-(2-arylvinyl)benzothiazoles 48-54, and a novel 5-substituted uracil derivative 55 of potential biological importance is also being reported. Similarly,the palladium-copper-catalyzed arylation of S-[2-(N-prop-2′-ynyl)aminophenyl]-N,N-dimethylthiocarbamate 58 with aryl iodides yields the disubstituted alkynes 59 which on cyclization with KOH in methanol leads to (E)-2-(2-aryl)methylidene-3,4-dihydro-2H-1,4-benzothiazines 61. The reaction of the diiodo compounds 12-14a, however, with 58 under palladium-copper-catalyzed reactions involves the participation of only one of the iodo groups in the heteroannulation process giving compounds 61i and 61j. These are amenable to further palladium-catalyzed reactions and afford polyunsaturated heteroaromatic compounds 62 and 63.

Full text of DOI:10.1021/jo001783+

J . Org. Chem. 2001, 66, 4563-4575
4563
P a lla d iu m -Cop p er Ca ta lyzed Syn th esis of Ben zofu sed
Heter ocycles w ith Tw o Heter oa tom s: Novel a n d High ly Regio- a n d
Ster eoselective Syn th eses of
(E)-2-(2-Ar ylvin yl)-3-tosyl-2,3-d ih yd r o-1,3-ben zoth ia zoles a n d
(E)-2-Alk yl(a r yl)id en e-3,4-d ih yd r o-2H-1,4-ben zoth ia zin es
Nitya G. Kundu* and Bidisha Nandi
Department of Organic Chemistry, Indian Association for the Cultivation of Science,
J adavpur, Calcutta - 700 032, India
ocngk@mahendra.iacs.res.in
Received December 26, 2000
A highly novel, general, and convenient palladium and copper-catalyzed procedure has been
developed for the synthesis of (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles 28-40. 3-(2-
Aminophenylthio)prop-1-yne 1 reacts with aryl iodides 2-14 under palladium-copper catalysis to
yield the disubstituted alkynes 15-27 which after tosylation undergo a novel cyclization with CuI
in the presence of triethylamine in THF to (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles
28-40 rather than to the expected 3-alkylidene-4-tosyl-3,4-dihydro-2H-1,4-benzothiazines 41. The
reaction is highly regio- and stereoselective. The synthesis of 2-(2-arylethyl)-3-tosylbenzothiazolines
42-47, 2-(2-arylvinyl)benzothiazoles 48-54, and a novel 5-substituted uracil derivative 55 of
potential biological importance is also being reported. Similarly, the palladium-copper-catalyzed
arylation of S-[2-(N-prop-2′-ynyl)aminophenyl]-N,N-dimethylthiocarbamate 58 with aryl iodides
yields the disubstituted alkynes 59 which on cyclization with KOH in methanol leads to (E)-2-(2-
aryl)methylidene-3,4-dihydro-2H-1,4-benzothiazines 61. The reaction of the diiodo compounds 12-
14a , however, with 58 under palladium-copper-catalyzed reactions involves the participation of
only one of the iodo groups in the heteroannulation process giving compounds 61i and 61j. These
are amenable to further palladium-catalyzed reactions and afford polyunsaturated heteroaromatic
compounds 62 and 63.
1,3-Benzothiazoles, benzothiazolines (2,3-dihydro-1,3-
benzothiazoles),1 and 1,4-benzothiazines2 have been of
considerable interest because of their profound biological
activities.3,4 Thus, the syntheses of benzothiazoles and
benzothiazines have attracted the attention of many
organic and medicinal chemists for decades.1,2,5,6 But to
our knowledge, there have been only one report7 on the
synthesis of these interesting heterocyclic structures
through palladium-catalyzed reactions. Palladium-cata-
lyzed arylation of olefins (Heck’s reaction)8 and cross-
coupling reactions9 have been of immense value for C-C
bond formation. Intense activities in these areas have
resulted in many elegant syntheses of various carbo-
cyclic10 and heterocyclic structures.11
We have been interested in the synthesis of various
heterocyclic structures because they are the integral part
of many naturally occurring and biologically active
compounds. With that objective, recently we have adopted
palladium-catalyzed reactions of terminal alkynes and
aryl halides12 with a nucleophilic group in the ortho-
position for the syntheses of a number of benzofused
heterocyclic structures with one heteroatom only, e.g.,
benzofurans,13 phthalides,14 quinolines and quinolones,15
isoindolinones,16 and flavones and flavanones.17 In an
alternative strategy, we have utilized the reactions of
mono-prop-2-ynyloxy or mono-prop-2-ynylamino aromatic
compounds with a nucleophilic group (OH, NH-Ts, CO2H)
in the ortho-position and aryl halides under palladium-
copper-catalyzed conditions for the synthesis of benzo-
fused heterocyclic structures with two heteroatoms, e.g.
1,4-benzodioxans,18 1,4-benzoxazines,19 1,4-benzodioxepi-
nones,20 and 4,1-benzoxazepinones.20 In an extension of
this reaction, we recently reacted 3-(2-aminophenylthio)-
prop-1-yne 1 with aryl iodides 2-14 under palladium-
copper catalysis to get the disubstituted alkynes 15-27
which, after tosylation, surprisingly cyclized to 2-substi-
tuted benzothiazolines 28-40 instead of the expected
3-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzothiazines 41
(Scheme 1, Table 1).21 In this report we describe the
detailed studies on the synthesis of the benzothiazolines,
their conversion to benzothiazoles, and a novel pal-
ladium-copper-catalyzed procedure for the synthesis of
1,4-benzothiazines.
* Corresponding author. Fax: +91-33-473-2805.
(1) For general discussion on benzothiazoles and benzothiazolines,
see (a) Campbell, M. M. Five-membered Ring Systems. In Compre-
hensive Organic Chemistry, Vol. 4, Heterocyclic Compounds; Barton,
D., Ollis, W. D., Eds., Pergamon Press: Oxford, 1979; Part 20, pp 976-
993. (b) Metzger, J . V. Thiazoles and their Benzo derivatives. In
Comprehensive Heterocyclic Chemistry; Katrizky, A. R., Rees, C. W.,
Eds.; Pergamon Press: Oxford, 1984; Vol. 6, pp 235-331.
(2) For discussions on benzothiazines, see (a) Landquist, J . K. Six-
membered Ring Systems. In Comprehensive Organic Chemistry;
Heterocyclic Compounds; Barton, D., Ollis, W. D., Sammes, P. G., Eds.;
Pergamon Press: Oxford, 1979; Vol. 4, pp 1092-1102. (b) Brown, C.;
Davidson, R. M. 1,4-Benzothiazines, dihydro-1,4-benzothiazines and
related compounds. Adv. Heterocycl. Chem. 1985, 38, 135-176. (c)
Gupta, R. R., Ed. Phenothiazines and 1,4-Benzothiazines: Chemical
and Biomedical Aspects. In Bioactive Molecules; Elsevier: Amsterdam,
Neth, 1988; Vol. 4. (d) Sainsbury, M. 1,4-Thiazines, 1,4-Benzothiazines,
Phenothiazines and Related Compounds. In Rodd’s Chemistry of
Carbon Compounds, 2nd ed.; Publisher: Elsevier: Amsterdam, Neth,
1998; Vol. 4 (Part G (partial)/Part H), pp 575-608.
10.1021/jo001783+ CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/06/2001

4564 J . Org. Chem., Vol. 66, No. 13, 2001
Kundu and Nandi
Sch em e 1. Syn th esis of (E)-2-(2-Ar ylvin yl)-3-tosyl-2,3-d ih yd r o-1,3-ben zoth ia zolesa
a
Reaction conditions: (a) (PPh3)2PdCl2 (3 mol %), CuI (6 mol %), Et3N, CH3CN, rt, 24 h; (b) p-TsCl, py, CH2Cl2, rt, 10 h; (c) CuI (40
mol %), Et3N, THF, reflux, 36 h.
Ta ble 1. Rea ction of 3-(2-Am in op h en ylth io)p r op -1-yn e 1
w ith Ar yl Iod id es 2-14 in th e P r esen ce of P a lla d iu m
Ca ta lyst, Cop p er (I) Iod id e, a n d Tr ieth yla m in e a n d
Su bsequ en t Cycliza tion of th e Disu bstitu ted Alk yn es
15-27 to
equiv) as a base in acetonitrile. Under the reaction
conditions, the normal C-arylation of the terminal alkyne
1 took place yielding the disubstituted alkynes 15-27
in good yields (68-77%) (Scheme 1 and Table 1).
We have found that for C-arylation of the terminal
alkyne 1, both bis(triphenylphosphine)palladium(II) chlo-
(E)-2-(2-Ar ylvin yl)-3-tosyl-2,3-d ih yd r o-1,3-ben zoth ia zoles
28-40 (Sch em e 1)a
(E)-2-(2-arylvinyl)-
disubstituted 3-tosyl-2,3-dihydro-
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aryl iodides
(ArI) Ar
alkynes,
1,3-benzothiazoles
entry
(yield %)b
(yield %)c
1
2
3
4
5
6
7
8
9
C6H5
2
15 (73)
16 (68)
17 (76)
18 (78)
19 (77)
20 (76)
21 (69)
22 (80)
23 (71)
24 (73)
28 (67)
29 (63)
30 (74)
31 (76)
32 (69)
33 (80)
34 (66)
35 (70)
36 (75)
37 (80)
1-naphthyl 3
2-naphthyl 4
3-ClC6H4 5
2-MeC6H4
4-MeC6H4
6
7
4-MeOC6H4 8
2-MeOCOC6H4
2-thienyl 10
9
10
2,4-dimethoxy-
pyrimidin-5-yl 11
5-iodo-2-thienyl 12
3-iodophenyl 13
11
12
13
25 (59)
26 (57)
27 (56)
38 (76)
39 (63)
40 (77)
4-iodophenyl 14
a
In all cases, (PPh3)2PdCl2 (3 mol %) and CuI (6 mol %) were
used. Yields are based on 1. c Yields are based on tosylates of
b
the disubstituted alkynes.
Resu lts a n d Discu ssion
3-(2-Aminophenylthio)prop-1-yne 1 was synthesized by
the propargylation of 2-aminothiophenol with propargyl
bromide in the presence of potassium carbonate. The
reaction of 1 with various aryl iodides 2-14 took place
under very mild conditions (25-30 °C, 24 h) in the
presence of (PPh3)2PdCl2 (3 mol %) as a catalyst, cuprous
iodide (6 mol %) as a cocatalyst, and triethylamine (4

Pd-Cu-Catalyzed Synthesis of Benzofused Heterocycles
J . Org. Chem., Vol. 66, No. 13, 2001 4565
Ta ble 2. Dep en d en ce of th e Yield of
3-(2-Am in op h en ylth io)-1-p h en ylp r op -1-yn e 15 on a
Ca ta lyst, a Coca ta lyst, a n d a Ba se
ride and cuprous iodide were essential as catalyst and
cocatalyst, respectively. The amount of the catalyst was
usually around 3 mol % of 1 whereas the cocatalyst was
cocatalyst
(mol %)
base
(equiv)
yield
(%)
entry
catalyst (mol %)
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2820.
1
2
3
(PPh3)2PdCl2 (3)
(PPh3)4Pd ()
Pd(OAc)2 (3)
CuI (6)
CuI (6)
CuI (6)
PPh3 (6)
-
CuI (6)
CuI (20)
CuI (6)
CuI (6)
Et3N (4)
Et3N (4)
Et3N (4)
74
20
28
4
5
6
7
8
(PPh3)2PdCl2 (3)
-
-
(PPh3)2PdCl2 (3)
(PPh3)2PdCl2 (3)
Et3N (4)
Et3N (4)
Et3N (4)
NaOAc (4)
K2CO3 (4)
37
0
12
0
15
used in amount of 6 mol %. With other palladium-
catalysts we used, e.g., tetrakistriphenylphosphine pal-
ladium (entry 2, Table 2) and palladium acetate (entry
3, Table 2), a much lower yield of the C-arylated product
15 was obtained. Cuprous iodide is an essential cocata-
lyst. In its absence the yield of 15 was much lower (37%,
entry 4, Table 2). Again, with cuprous iodide alone (no
palladium catalyst, entry 6, Table 2), a poor yield (12%)
of the diarylated alkyne 15 was obtained. Similarly,
studies with other bases, e.g., sodium acetate (entry 7)
and potassium carbonate (entry 8) revealed that Et3N is
the best base for the palladium-catalyzed arylation
reactions. Acetonitrile was found to be the best solvent
for C-arylation reaction. The use of triethylamine both
as the solvent and the base led to poorer yields due to
incomplete solubility of some starting materials in Et3N.
The use of DMF as the solvent led to the formation of
colored materials and some polymerization of the reaction
mixture. The reactions were carried out at room temper-
ature and a reaction period of 24 h was found to be the
optimum. Various substituted aryl iodides were used for
the C-arylation reaction under palladium-copper cataly-
sis, and it was observed that substituents in the aromatic
ring did not affect the yields considerably. However, in
the case of the diiodo compounds, yields of the diynes 25-
27 (Scheme 1, Table 1) were much lower from the loss of
the starting material 1 due to polymerization. It is
essential to use the free amine 1 for the success of the
arylation reaction. The use of the corresponding tosylate
with aryl iodides under normal palladium-copper ca-
talysis conditions did not give any disubstituted alkyne.
However, the use of excess of CuI (40 mol %) in the
arylation reaction of the tosylate of 1 led to depropargy-
lation and concurrent S-arylation.22 Although in the case
of the synthesis of (Z)-2-alkyl(aryl)idene-2,3-dihydroben-
zodioxins,18 we have observed that the arylation of the
terminal alkyne and subsequent cyclization did take
place in a single step, in the case of the attempted
synthesis of the corresponding benzothiazines the cy-
clization of the disubstituted alkynes 15-27 did not take
place in a single step under palladium-copper catalysis.
Also we failed to cyclize the free amines 15-27 under
(14) (a) Kundu, N. G.; Pal, M. J . Chem. Soc., Chem. Commun. 1993,
86-88. (b) Kundu, N. G.; Pal, M.; Nandi, B. J . Chem. Soc., Perkin
Trans. 1 1998, 561-568.
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Commun. 1996, 1067-1068. (b) Chowdhury, C.; Chaudhuri, G.; Guha,
S.; Mukherjee, A. K.; Kundu, N. G. J . Org. Chem. 1998, 63, 1863-
1871.
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Lett. 1993, 34, 1625-1628. (b) Mahanty, J . S.; De, M.; Das, P.; Kundu,
N. G. Tetrahedron 1997, 53, 13397-13418.
(19) (a) Chaudhuri, G.; Chowdhury, C.; Kundu, N. G. Synlett 1998,
1273-1275. (b) Kundu, N. G.; Chaudhuri, G.; Upadhyay, A. J . Org.
Chem. 2001, 66, 20-29.
(16) (a) Khan, M. W.; Kundu, N. G. Synlett 1997, 1435-1437. (b)
Kundu, N. G.; Khan, M. W.; Mahanty, J . S. J . Chem. Res. (S) 1999,
460-461; J . Chem. Res. (M) 1999, 1901-1918. (c) Kundu, N. G.; Khan,
M. W.; Mukhopadhyay, R. Tetrahedron 1999, 55, 12361-12376. (d)
Kundu, N. G.; Khan, M. W. Tetrahedron 2000, 56, 4777-4792.
(17) De, M.; Majumdar, D. P.; Kundu, N. G. J . Indian Chem. Soc.
1999, 76, 665-674.
(20) Chaudhuri, G.; Kundu, N. G. J . Chem. Soc., Perkin Trans. 1
2000, 775-779.
(21) A preliminary account has appeared: Nandi, B.; Kundu, N. G.
Org. Lett. 2000, 2, 235-238.
(22) Nandi, B.; Das, K.; Kundu, N. G. Tetrahedron Lett. 2000, 41,
7259-7262.

4566 J . Org. Chem., Vol. 66, No. 13, 2001
Kundu and Nandi
Sch em e 2
various conditions, e.g., (i) Pd(OAc)2 (5 mol %), LiCl (0.7
mmol), K2CO3 (1.8 mmol), 80 °C, 24 h23, (ii) NaOEt (2.5
equiv) in EtOH, reflux, 30 h,20 (iii) NaH in THF, reflux,
20 h. However, the corresponding tosylates of 15-27,
which were obtained in high yields (88-96%), could be
easily cyclized by refluxing for 36 h in THF in the
presence of CuI (40 mol %) and Et3N (4 equiv) in fairly
good yields (63-80%, Table 1). Other cyclizing agents,
e.g., (i) K2CO3 (2 equiv) in acetone, reflux for 24 h, (ii)
KOH (10 equiv) in MeOH, reflux, 30 h, and (iii) NaOEt
in EtOH, reflux for 36 h, yielded either the starting
material or the detosylated material. Use of other agents,
like NaH (2 equiv) in THF or CH3CN and PdCl2 (10 mol
%) in CH3CN in the presence of Et3N (4 equiv), reflux,
30 h, led to the formation of polymeric materials. We
noticed that for the cyclization step, considerable amount
of CuI (40 mol %) was needed. In the absence of CuI, with
Et3N in THF alone 5% yield of cyclic product 28 was
obtainedssimilarly, 6 mol % of CuI gave 10% yield, 20
mol % gave 30% yield, 30 mol % gave 45% yield, and 40
mol % gave 67% yield of 28. Higher percentage of CuI
led to a decline in yield. Also for cyclization, Et3N plays
a significant role since no cyclization was observed in the
absence of Et3N. The use of K2CO3 or NaOAc in place of
Et3N did not give any products. THF was found to be
the best solvent for cyclization. The use of other solvents
such as CH3CN or DMF led to some polymeric materials.
In contrast to our observations in the case of the
synthesis of 2-alkyl(aryl)idene-2,3-dihydro-1,4-benzodiox-
ins18 and 2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzox-
azines,19 cyclization did not lead to the expected 3-alkyl-
(aryl)idene-1,4-benzothiazines 41 but to the (E)-2-(2-
arylvinyl)-3-tosyl-1,3-benzothiazolines (28-40).
Ta ble 3. Syn th esis of
2-(2-Ar yleth yl)-3-tosylben zoth ia zolin es 42-47 (Sch em e 2)
2-(2-arylvinyl)-3-tosyl- 2-(2-arylethyl)-3-tosyl- yield
entry
benzothiazolines (Ar)
benzothiazolines
(%)
1
2
3
4
5
6
28, C6H5
42
43
44
45
46
47
96
98
97
91
95
97
29, 1-naphthyl
30, 2-naphthyl
33, 4-MeC6H4
34, 4-MeOC6H4
35, 2-MeOCOC6H4
Sch em e 3
arylvinyl)-3-tosylbenzothiazolines 28-37 through pal-
ladium-copper-catalyzed reactions using readily avail-
able starting materials and under very mild conditions.
Also, the synthesis of the bis-benzothiazoline derivatives,
e.g., 38-40 (Table 1) adds in applicability of our synthetic
protocol. To extend the scope, compounds 28-30, 33-
35 could be hydrogenated with Pd/C (10%) and hydrogen
to the corresponding saturated derivatives, e.g., 2-(2-
aryl)ethyl-3-tosylbenzothiazolines 42-47 (See Scheme 2,
Table 3).
Another important outcome has been the synthesis of
2-(2-arylvinyl)benzothiazoles 48-54 which were easily
obtained by dehydrotosylation of 2-(2-arylvinyl)-3-tosyl-
benzothiazolines 28-30, 33-35, 39 with potassium tert-
butoxide in DMF at room temperature for 2 h in excellent
yields (Scheme 3, Table 4).
A very significant aspect of our synthetic protocol is
the generation of a number of 2-arylvinyl-substituted
benzothiazolines, benzothiazoles, and bis-benzothiazoline
The structures of the products 28-40 follow from (1)
1
the absence of a propargylic CH2 signal both in H NMR
and 13C NMR spectra, (2) the presence of -CH-CHd
1
CH- signals in H NMR spectra, (3) subsequent conver-
sion of 2-(2-arylvinyl)-3-tosylbenzothiazolines to 2-(2-
arylvinyl)benzothiazoles (see discussion below and Experi-
mental Section), (4) conversion of 2-[2-(m-chlorophenyl)-
vinyl]benzothiazoline 31 to m-chlorocinnamaldehyde by
treatment with silver nitrate in Et3N-phosphate buffer
according to the procedure of Corey and Boger,24 and (5)
X-ray diffraction studies on 29.25 The configuration of the
double bond was established from the splitting constants
between two vinylic hydrogens at δ 6.25 and 6.69 (J )
15 Hz). Mechanistically21 the formation of the benzothia-
zolines can be explained on the basis of (i) the usual Pd0-
mediated C-arylation12c leading to the disubstituted
alkynes 15-27 and (ii) subsequent isomerization of the
propargylic tosylates to allenic intermediates21,26 which
then undergo cyclization27 to (E)-2-(2-arylvinyl)-3-tosyl
benzothiazolines 28-40.
(26) Inspite of our best efforts, we could not isolate any allenic
intermediates. They seem to be extremely reactive and undergo rapid
cyclization to the benzothiazolines 28-40. For propargyl to allenic
isomerization, see, (a) Garratt, P. J .; Neoh, S. B. J . Am. Chem. Soc.
1975, 97, 3255-3256. (b) Midland, M. M. J . Org. Chem. 1977, 42,
2650-2657. (c) Flood, T.; Peterson, P. E. J . Org. Chem. 1980, 45, 5006-
5007. (d) Brandsma, L.; Verkruijsee, H. D. Synthesis of Acetylenes,
Allenes, and Cumulenes; Elsevier: New York, 1980. (e) Pasto, D. J .
Tetrahedron 1984, 40, 2805-2827. (f) Tsuji, J .; Sugiura, T.; Minami,
I. Tetrahedron Lett. 1986, 27, 731-734. (g) Marshall, J . A.; Yu, R. H.;
Perkins, J . F. J . Org. Chem. 1995, 60, 5550-5555.
(27) For nucleophilic additions to allenes, see (a) Nixon, N. S.;
Scheinmann, F. Tetrahedron Lett. 1983, 24, 597-600. (b) Tanaka, H.;
Kamayema, Y.; Sumida, S.-i.; Yamada, T.; Tokumaru, Y.; Shiroi, T.;
Sasaoka, M.; Taniguchi, M.; Torii, S. Synlett. 1991, 888-890. (c) Kant,
J .; Roth, J . A.; Fuller, C. E.; Walker, D. G.; Benigni, D. A.; Farina, V.
J . Org. Chem. 1994, 59, 4956-4966. (d) Su, C.-C.; Chen, J .-T.; Leu,
G.-H.; Wang, Y. J . Am. Chem. Soc. 1994, 116, 4999-5000. (e) Marshall,
J . A.; Sehon, C. A. J . Org. Chem. 1995, 60, 5966-5968. (f) Marshall,
J . A.; Wolf, M. A.; Wallace, E. J . Org. Chem. 1997, 62, 367-371. (g)
Larock, R. C.; Tu, C.; Pace, P. J . Org. Chem. 1998, 63, 6859-6866. (h)
Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem. Rev. 2000,
100 (8), 3067-3125.
Scop e of th e Rea ction . We have shown the utility of
our reaction in the synthesis of a number of (E)-2-(2-
(23) Larock, R. C.; Yum, E. K. J . Am. Chem. Soc. 1991, 113, 6689-
6690.
(24) Corey, E. J .; Boger, D. L. Tetrahedron Lett. 1978, 5-8.
(25) Maiti, S.; Mukherjee, M.; Nandi, B.; Helliwell, M.; Kundu, N.
G. Acta Crystallogr. 2000, C56, 992-994.

Pd-Cu-Catalyzed Synthesis of Benzofused Heterocycles
J . Org. Chem., Vol. 66, No. 13, 2001 4567
Sch em e 5a
Ta ble 4. Syn th esis of 2-(2-Ar ylvin yl)ben zoth ia zoles
48-54 (Sch em e 3)
2-(2-arylvinyl)-3-tosyl-
benzothiazolines (Ar)
2-(2-arylvinyl)-
benzothiazoles
yield
(%)
entry
1
2
3
4
5
6
7
28, C6H5
48
49
50
51
52
53
54
74
70
78
75
76
73
71
29, 1-naphthyl
30, 2-naphthyl
33, 4-MeC6H4
34, 4-MeOC6H4
35, 2-MeOCOC6H4
39, 3-iodophenyl
Sch em e 4
derivatives. Since benzothiazoles and benzothiazolines
are of biological importance, we believe some of the
compounds we have synthesized could have some biologi-
cal activities and studies are in progress in this area.
Also, we have converted 37 by treatment with TMSCl
and NaI28 in acetonitrile to 2-[2-(uracil-5-yl)vinyl]-3-
tosylbenzothiazoline 55, a uracil derivative with a novel
substituent in the 5-position of the uracil ring (Scheme
4). Since 5-substituted uracil compounds29 are of impor-
tance as anticancer and antiviral agents, 55 and the
analogous nucleosides could be biologically important.
Syn th esis of 2-Alk yl(a r yl)id en e-3,4-d ih yd r o-2H-
1,4-ben zoth ia zin es. The synthesis of 2-alkyl(aryl)idene-
3,4-dihydro-2H-1,4-benzothiazines 61 was accomplished
through the palladium-copper-catalyzed reactions of
S-[2-(N-prop-2′-ynyl)aminophenyl]-N,N-dimethylthiocar-
bamate 58 with aryl iodides leading to the disubstituted
alkynes 59 and the subsequent cyclization of the later
with KOH in methanol (Scheme 5 and Table 5).
Since direct propargylation of 2-aminothiophenol leads
to almost exclusive substitution at the thiol group, we
utilized S-(2-nitrophenyl)-N,N-dimethylthiocarbamate30
56 as the starting material. The dimethyl carbamoyl
group was found to be very suitable as a thiol protecting
group31 since it could be easily removed by alkaline
hydrolysis during the subsequent cyclization step (Scheme
5, step v). Compound 56 was reduced with iron powder
in acetic acid to S-(2-aminophenyl)-N,N-dimethyl thio-
carbamate 57 in excellent yield (89%). This on usual
propargylation with propargyl bromide in acetone in the
presence of potassium carbonate yielded S-[2-(N-prop-
2′-ynyl)aminophenyl]-N,N-dimethylthiocarbamate 58.
Compound 58 underwent C-arylation with aryl iodides
in the presence of bis(triphenylphosphine) palladium(II)
chloride (3.3-3.5 mol %) as a catalyst, cuprous iodide (6
mol %) as a cocatalyst, and triethylamine as a base in
acetonitrile under very mild conditions (stirring at room
a
Reaction conditions: (i) Fe in AcOH; (ii) propargyl bromide,
K2CO3 in acetone; (iii) (PPh3)2PdCl2, CuI, Et3N in CH3CN at room
temperature, 24 h; (iv) RX, K2CO3, acetone, reflux, 10 h; (v) KOH
in MeOH, reflux, 24 h.
Ta ble 5. Rea ction of
S-[2-(N-P r op -2′-yn yl)a m in op h en yl]-N,N-d im eth yl
Th ioca r ba m a te 58 w ith Ar yl Iod id es u n d er
P a lla d iu m -Cop p er Ca ta lysis To F or m Disu bstitu ted
Alk yn es 59 a n d Th eir Su bsequ en t Cycliza tion to
2-Alk yl(a r yl)id en e-3,4-d ih yd r o-2H-1,4-ben zoth ia zin es 61
(Sch em e 5)
disubstituted
alkynes,
2-alkylidene
benzothiazines
61(%)b
aryl iodides (ArI)
Ar
entry
59 and 60 (%)a
1
2
3
4
5
6
7
8
9
C6H5
1-naphthyl 3
2-naphthyl 4
3-ClC6H4 5
2-MeC6H4
4-MeC6H4
4-MeOC6H4 8
2-thienyl 10
5-iodo-2-thienyl 12
4-iodophenyl 14
2-iodophenyl 14a
2
59a (95)
59b (90)
59c (91)
59d (93)
59e (92)
59f (92)
59g (95)
59h (90)
59i (59)
59j (65)
59k (68)
60a (96)
60b (88)
61a (70)
61b (74)
61c (75)
61d (76)
61e (79)
61f (81)
61g (77)
61h (82)
61i (75)
61j (79)
61k (69)
61l (95)
61m (90)
6
7
10
11
12c,e
13d,e
a
b
Yields are based on 58. Yields are based on disubstituted
alkynes 59 or 60. c 60a was obtained by methylation of 59f with
d
MeI, K2CO3 in acetone, reflux, 10 h. 60b was obtained by
benzylation of 59f with BnBr, K2CO3 in acetone, reflux, 15 h.
e Yields of 60a and 60b are based on 59f.
temperature for 24 h) yielding the disubstituted alkynes,
S-[2-(N-3′-aryl-prop-2′-ynyl)aminophenyl]-N,N-dimeth-
ylthiocarbamates 59, in excellent yields (Scheme 5, Table
5). The use of bis-triphenylphosphine palladium(II) dichlo-
ride as a catalyst was found to give the optimum yield
(95%) (entry 1, Table 6). When tetrakistriphenylphos-
phine palladium(0) was used as the catalyst (entry 2,
Table 6), the yield was much lower (23%). The cuprous
iodide was found to be an essential cocatalyst. In its
absence (entry 3, Table 6), 28% of the disubstituted
alkyne was obtained whereas in the absence of the
palladium catalyst but in the presence of CuI alone, 7%
of 59a (entry 4, Table 6) was obtained. Et3N was found
to be essential as a base for the coupling reaction. In its
absence, no coupled products were obtained. The use of
others bases, e.g., NaOAc or K2CO3, gave a very poor yield
(28) Morita, J .; Okamoto, Y.; Sakurai, H. J . Chem. Soc., Chem.
Commun. 1978, 874-875.
(29) (a) Heidelberger, C. Pyrimidine and Pyrimidine Anti-metabo-
lites in Cancer Medicine; Holland, J . F.; Frei, E., Eds.; Lea and Febiger:
Philadelphia, PA, 1984; pp 801-824. (b) De Clercq, E. J . Med. Chem.
1995, 38, 2491-2517. (c) Kundu, N. G.; Das, B.; Spears, C. P.;
Majumdar, A.; Kang, S. I. J . Med. Chem. 1990, 33, 1975-1979. (d)
Kundu, N. G.; Mahanty, J . S.; Chowdhury, C.; Dasgupta, S. K.; Das,
B.; Spears, C. P.; Balzarini, J .; De Clercq, E. Eur. J . Med. Chem. 1999,
34, 389-398 and references therein.
(30) Newman, M.; Karens, H. A. J . Org. Chem. 1966, 31, 3980-
3984.
(31) Thanks are due to Professor Asish De of our department for
bringing this to our attention.

4568 J . Org. Chem., Vol. 66, No. 13, 2001
Kundu and Nandi
Ta ble 6. Dep en d en ce of th e Yield of
S-[2-(N-3′-Ar ylp r op -2′-yn yl)a m in op h en yl]-N,N-d im eth yl
Th ioca r ba m a te 59a on a Ca ta lyst, a Coca ta lyst, a n d a
Ba se
Sch em e 6
entry
catalyst
cocatalyst
base
yield (%)
1
2
3
4
5
(PPh3)2PdCl2
(PPh3)4Pd
(PPh3)2PdCl2
-
CuI
CuI
-
CuI
CuI
Et3N
Et3N
Et3N
Et3N
K2CO3
95
23
28
7
(PPh3)2PdCl2
14
The amount of a catalyst used was 3.4-3.5 mol %, cocatalyst
(6 mol %) except in case of entry 4 where 10 mol % of CuI was
used, and the amount of base used was 4 equiv. The reactions were
carried in CH3CN at room temperature for 24 h.
Mech a n ism . Mechanistically, the terminal alkyne 58
undergoes the usual C-arylation. catalyzed by Pdo gener-
ated from bis(triphenylphosphine)palladium(II) dichlo-
ride, as suggested by Sonogashira and co-workers,12c
leading to the disubstituted alkynes 59. The disubstituted
alkynes then on hydrolysis cyclized to 61. Interestingly,
the cyclization of the disubstituted alkynes 59 led to
2-alkylidene benzothiazines 61 of E-configuration in
contrast to the formation of (Z)-2-alkylidene-2,3-dihydro-
1,4-benzodioxins18 and (Z)-2-alkylidene-3,4-dihydro-2H-
benzoxazines19 in analogous cyclization reactions. No
compounds with Z-configuration were observed. This
could be explained by syn-addition34 caused by an exo-
dig attack on the alkyne moiety of the thiol group
resulting from the hydrolysis of the dimethylthiocarbam-
oyl group.
Scop e a n d Lim ita tion s. The (E)-2-alkylidene-3,4-
dihydro-2H-1,4-benzothiazines 61 were found to decom-
pose slowly in solution in CHCl3, diethyl ether, ethyl
acetate, and petroleum ether. Hence, various attempts
to grow single crystals of 61 for X-ray diffraction studies
by slow crystallization failed. Also, during hydrogenation
over palladium on charcoal in solvents such as ethyl
acetate, MeOH, glacial AcOH, compounds 61 were broken
down into a number of unidentified components. Thus,
we could not synthesize the corresponding saturated
compounds, 2-alkyl-3,4-dihydro-2H-1,4-benzothiazines.
We have also observed that the reactions of diiodo-
aromatic compounds led to compounds 61i, 61j, and 61k .
Interestingly, these iodo-substituted benzothiazines 61i-k
could undergo further palladium-catalyzed reactions
giving rise to variously substituted heteroaromatic com-
pounds (Scheme 6).
of 59a (entry 5, Table 6). CH3CN was found to be the
best solvent for C-arylation reaction. The use of DMF
gave rise to some polymeric materials, lowering the yield
considerably. Also, due to insolubility of the starting
material 58 in Et3N, it could not be used as a solvent.
The C-arylation reaction was found to give excellent
yields (90-95%) of the disubstituted alkynes 59a -59h
when monoiodo aromatic compounds were used as aryl
iodides (entries 1-8, Table 5). The reaction was tolerant
to various substituents in the aromatic ring. When diiodo
compounds were used, the yields were somewhat lower
(entries 9-11, Table 5). It was observed that only one of
the iodide group entered the C-arylation reactions of 58.
The cyclization of the disubstituted alkynes 59 was
carried out by refluxing them with excess of KOH (10
equiv) in methanol. The use of lesser amount of KOH
led to poorer yields. The use of other bases, e.g., NaOEt
in EtOH, KOBu-t in t-BuOH, DMF or CH3CN did not
yield the cyclized materials. It was noticed that the
presence of an alkyl or benzyl substituent on the N-atom
(entries 12 and 13, Table 5) improves the yield (90-95%)
of the cyclized products.
The structures of the cyclized products as 2-alkylidene-
3,4-dihydro-2H-1,4-benzothiazines 61 follow from their
analytical and spectroscopic (IR, 1H NMR, and 13C NMR)
1
data. Particularly, in the H NMR spectra, the presence
of singlets at δ 3.69-4.01 (NCH2) and δ 6.16-6.81
(CdCH) and in the 13C NMR absorptions at δ 49.3-56.3
(NCH2) and 113.9-120.1 (dCH) confirm the 2-alkylidene-
3,4-dihydro-2H-1,4-benzothiazine structures. We have
not observed the formation of any seven-membered ring
compounds or any five-membered ring compounds, thus
pointing to the regiospecificity of the cyclization reaction.
The compounds were assigned the E-configuration on the
basis of the chemical shift (δ 6.16-6.81) values of the
vinylic hydrogen which is considerably shifted downfield
due to deshielding effect32 of the sulfur atom in the
thiazine ring compared to the chemical shift of the vinylic
hydrogens of (Z)-2-alkylidene-3,4-dihydro-2H-1,4-benz-
oxazines (δ 5.32-6.03)19 and for the vinylic hydrogens of
(Z)-2-alkylidene-2,3-dihydrobenzodioxins (δ 5.52-5.92).18
Con clu sion
Starting from 2-aminothiophenol, a readily available
starting material, we have developed a highly general
method for the synthesis of (E)-2-(2-arylvinyl)-3-tosyl-2,3-
dihydro-1,3-benzothiazoles. The method involves two
metal-catalyzed reactions, e.g., (i) a palladium-copper-
catalyzed C-arylation of terminal alkynes giving rise to
the disubstituted alkynes 15-27, (ii) a unique copper-
catalyzed cyclization which presumably involves a pro-
pargyl-allenic rearrangement21,26 and subsequently a
nucleophilic attack by the tosylamide group on the
3
Also, the J CH values between the vinylic proton and the
methylenic carbon (NCH2) of the heterocyclic ring con-
firmed the E-configuration of the exocyclic double bond.
The 3J CH values of more than 7 Hz or less than 5 Hz have
been attributed to E- and Z-isomers, respectively.33,18,19
(33) (a)Vogeli, U.; van Philipsborn, W. Org. Magn. Reson. 1975, 7,
617-627. (b) Cabiddu, S.; Floris, C.; Melis, S.; Sotgiu, F.; Cerioni, G.
J . Heterocycl. Chem. 1986, 23, 1815-1820.
(34) The syn-addition to triple bond has been authenticated in the
literature: (a) Bailey, W. F.; Ovaska, T. V. Tetrahdron Lett. 1990, 31,
627-630. (b) Weingarten, M. D.; Padwa, A. Tetrahedron Lett. 1995,
36, 4717-4720. Another explanation could be that during cyclization,
compounds of Z configuration were formed which immediately got
isomerised to benzothiazines having E configuration.
3
In our case, the J CH values were found to be 7.5 Hz for
compounds 61a , 61b, 61d , 61e, and 61f.
(32) (a) J ager, V.; Gunther, H. J . Tetrahedron Lett. 1977, 2543-
2546. (b) Yamamoto, M. J . Chem. Soc., Chem. Commun. 1978, 649-
650. (c) Arcadi, A.; Burini, A.; Cacchi, S.; Delmastro, M.; Marinelli, F.;
Pietrohi, B. R. J . Org. Chem. 1992, 57, 976-982.

Pd-Cu-Catalyzed Synthesis of Benzofused Heterocycles
J . Org. Chem., Vol. 66, No. 13, 2001 4569
terminal carbon of the allenic moiety.21,27 The process is
highly regio- and stereoselectivesonly five-membered
ring formation took place leading to the benzothiazolines.
No six-membered compounds, e.g., the expected ben-
zothiazines, or seven-membered ring heterocycles were
obtained. The method not only requires cheap readily
available starting materials and reagents, but is also
carried out under mild reaction conditions. A number of
(E)-2-(2-arylvinyl)-3-tosylbenzothiazolines 28-40, their
saturated derivatives, e.g., 2-(2-arylethyl)-3-tosylbenzo-
thiazolines 42-47, and also 2-arylvinylbenzothiazoles
48-54 could be accessed by our procedure. An uracil
derivative 55 with a 2-(3-tosyl-2,3-dihydro-1,3-benzothia-
zol-2-yl) substituent at C-5 of the uracil ring and of
potential biological significance has been synthesized. We
have also described a novel procedure for the synthesis
of 2-alkylidene-1,4-benzothiazines 61 where a palladium-
copper-catalyzed arylation of terminal alkynes played a
crucial role in the synthetic sequence. Interestingly, the
2-alkylidene benzothiazines were of the E-configuration
instead of the expected Z-configuration.
mesh), the eluent being light petroleum/ethyl acetate (95/5,
V/V) to afford 15 as a light yellow oil; IR (liquid film) 3460,
1
3370, 1605, 1480 cm-1; H NMR (300 MHz, CDCl3) δ 3.62 (s,
2H), 4.27 (brs, 2H), 6.42-6.69 (m, 2H), 7.12 (td, J ) 9, 1.5 Hz,
1H), 7.21-7.25 (m, 3H), 7.29-7.34 (m, 2H), 7.48 (dd, J ) 7.8,
1.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 24.5, 84.3, 86.2,
115.4, 116.9, 118.9, 123.6, 128.6, 128.7, 131.2, 132.1, 137.6,
149.3; 13C NMR (75 MHz, CDCl3, DEPT 135) δ 24.2 (inverted),
115.1, 118.6, 128.3, 128.4, 130.9, 131.8, 137.3. Anal. Calcd for
C
15H13NS: C, 75.27; H, 5.47; N, 5.85. Found: C, 75.34; H, 5.45;
N, 5.71.
Tosyla te of 15 was synthesized by stirring the alkyne 15
(400 mg, 1.79 mmol) in CH2Cl2 (20 mL) with p-TsCl (340 mg,
1.79 mmol) and pyridine (430 mg, 5.44 mmol) at room
temperature for 10 h. Pyridine and dichloromethane were then
removed under vacuum, and the residue was diluted with
water followed by extraction with CHCl3. The organic layer
was washed with water and dried, and solvent was distilled
off. Purification of the crude product by column chromatogra-
phy on silica gel (60-120 mesh), the eluent being light
petroleum/ethyl acetate (90/10, V/V), afforded the tosylate as
a white solid; mp 85 °C; IR 3250, 1600, 1585, 1580, 1475 cm-1
;
1H NMR (300 MHz, CDCl3) δ 2.32 (s, 3H), 3.43 (s, 2H), 7.04
(td, J ) 7.5, 1.2 Hz, 1H), 7.16 (d, J ) 8.1 Hz, 2H), 7.25-7.34
(m, 6H), 7.55 (dd, J ) 7.8, 1.5 Hz, 1H), 7.66 (d, J ) 8.1 Hz,
3H), 7.95 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 22, 26.2, 84.6,
85.2, 120.6, 122.9, 123.8, 125.3, 127.6, 128.7, 128.8, 130, 131.2,
132, 136.5, 137.2, 139.8, 144.4. 13C NMR (75 MHz, CDCl3,
DEPT 135) δ 21.7, 25.9 (inverted), 120.3, 125, 127.3, 128.4,
128.5, 129.8, 130.9, 131.7, 136.9. Anal. Calcd for C22H19NO2S2:
C, 67.15; H, 4.86; N, 3.56. Found: C, 66.95; H, 4.96; N, 3.54.
Compound 16-27 and their tosylates were synthesized
following the procedure for 15 and the corresponding tosylate.
3-(2-Am in oph en ylth io)-1-(1-n aph th yl)pr op-1-yn e (16): light
brown oil; IR (liquid film) 3460, 3360, 1605, 1585, 1500, 1480
Exp er im en ta l Section
Melting points are uncorrected. Reactions were performed
under argon atmosphere. Bis(triphenylphosphine)palladium-
(II) dichloride was obtained from Aldrich Chemical Co.,
Milwaukee, WI. Light petroleum used was the fraction boiling
between 60 and 80 °C. Column chromatography was performed
on silica gel (60-120 mesh). TLC was done on 60F-254
precoated sheets. Aryl iodides were prepared according to the
procedure given for the synthesis of iodobenzene.35a 2-Iodothio-
phene,35b 2,5-diiodothiophene,35b and 5-iodo-2,4-dimeth-
oxypyrimidine35c were synthesized according to the known
procedures. 1H NMR spectra in CDCl3 solutions were recorded
at 300 MHz and that in CCl4 solutions at 60 MHz. 13C NMR
1
cm-1; H NMR (60 MHz, CCl4) δ 3.72 (s, 2H), 4.10 (brs, 2H),
6.46-7.03 (m, 3H), 7.13-7.79 (m, 7H), 8.00-8.16 (m, 1H).
Anal. Calcd for C19H15NS: C, 78.83; H, 5.25; N, 4.83. Found:
C, 78.71; H, 5.16; N, 4.72.
3
Tosyla te of 16: light brown gum. IR (liquid film) 3280,
1600, 1485 cm-1; 1H NMR (60 MHz, CCl4) δ 2.33 (s, 3H), 3.36
(s, 2H), 6.92-7.10 (m, 3H), 7.29-7.53 (m, 6H), 7.59-7.82 (m,
6H), 7.89 (s, 1H). Anal. Calcd for C26H21NO2S2 C, 70.42; H,4.77;
N,3.15. Found: C, 70.60; H, 4.81; N, 3.23.
3-(2-Am in op h en ylth io)-1-(2-n a p h th yl)p r op -1-yn e (17):
white solid; mp 71 °C; IR 3470, 3365, 1600, 1580 cm-1; 1H NMR
(300 MHz, CDCl3) δ 3.69 (s, 2H), 4.41 (brs, 2H), 6.71 (d, J )
7.2 Hz, 2H), 7.18 (t, J ) 7.8 Hz, 1H), 7.35-7.44 (m, 3H), 7.53
(d, J ) 7.8 Hz, 1H), 7.68-7.76 (m, 3H), 7.84 (s, 1H). Anal. Calcd
for C19H15NS: C, 78.83; H, 5.25; N, 4.83. Found: C, 78.91; H,
5.40; N, 4.81.
spectra were recorded at 75 MHz. J CH values were obtained,
performing 13C NMR experiments under proton-coupled mode.
Syn t h esis of 3-(2-Am in op h en ylt h io)p r op -1-yn e (1).
2-Aminothiophenol (1 g, 0.8 mmol) in dry acetone (15 mL) was
stirred with anhydrous K2CO3 (1.12 g, 8 mmol) at room
temperature for 4 h. Propargyl bromide (0.95 g, 8 mmol) was
added under ice-cooling, and the reaction mixture was heated
under reflux for 15 h. After removal of acetone, the residue
was diluted with H2O and extracted with CHCl3. The organic
layer was washed with H2O and dried (anhyd Na2SO4). After
removal of the solvent, a brown residue was obtained which
was purified by column chromatography on silica gel (60-120
mesh) using petroleum ether/ethyl acetate mixture (95/5, V/V)
as eluent. Compound 1 was obtained as a light yellow oil (960
Tosyla te of 17: white solid; mp 91 °C; IR 3250, 1590, 1470
cm-1 1H NMR (60 MHz, CCl4) δ 2.19 (s, 3H), 3.43 (s, 2H),
;
mg, 74%). IR (liquid film) 3460, 3360, 3290, 1608 cm-1 1H
;
6.82-7.43 (m, 8H), 7.56-7.76 (m, 7H), 7.95 (s, 1H). Anal. Calcd
for C26H21NO2S2: C, 70.39; H, 4.77; N, 3.15. Found: C, 70.51;
H, 4.65; N, 3.05.
NMR (60 MHz, CCl4) δ 2.06 (t, J ) 3 Hz, 1H), 3.33 (d, J ) 3
Hz, 2H), 4.2 (s, 2H), 6.53-6.69 (m, 2H), 6.92-7.46 (m, 2H).
Anal. Calcd for C9H9NS: C, 66.22; H, 5.56; N, 8.58. Found: C,
65.98; H, 5.57; N, 8.30.
3-(2-Am in op h en ylth io)-1-(3-ch lor op h en yl)p r op -1-yn e
(18): light yellow oil; IR (liquid film) 3440, 3360, 1600, 1590
1
cm-1; H NMR (60 MHz, CCl4) δ 3.56 (s, 2H), 4.23 (brs, 2H),
Typ ica l P r oced u r e for th e Syn th esis of 3-(2-Am i-
n op h en ylth io)-1-p h en ylp r op -1-yn e (15). 3-(2-Aminophe-
nylthio)prop-1-yne 1 (600 mg, 3.67 mmol) and iodobenzene 2
(730 mg, 3.67 mmol) were stirred in the presence of (PPh3)2-
PdCl2 (90 mg, 0.13 mmol), CuI (42 mg, 0.22 mmol), and
triethylamine (1.45 g, 14.33 mmol) in acetonitrile (10 mL) at
room temperature under argon atmosphere for 24 h. After
removal of the solvent under reduced pressure, the residue
was treated with H2O and extracted with CHCl3. The organic
layer was washed with H2O and dried (anhyd Na2SO4) and
solvent was distilled off to yield a brown gum which was
purified by column chromatography on silica gel (60-120
6.46-6.72 (m, 2H), 6.92-7.53 (m, 6H). Anal. Calcd for C15H12
-
ClNS: C, 65.79; H, 4.41; N, 5.11. Found: C, 65.86; H, 4.37; N,
5.16.
Tosyla te of 18: pale yellow gum; IR (liquid film) 3280,
1595, 1580 cm-1; 1H NMR (60 MHz, CCl4) δ 2.33 (s, 3H), 3.39
(s, 2H), 6.83-7.46 (m, 9H), 7.59-7.72 (m, 3H), 7.89 (s, 1H).
Anal. Calcd for C22H18ClNO2S2: C, 61.73; H, 4.24; N, 3.27.
Found: C, 61.66; H, 4.21: N, 3.32.
3-(2-Am in op h e n ylt h io)-1-(2-m e t h ylp h e n yl)p r op -1-
yn e (19): light brown oil; IR (liquid film) 3460, 3360, 1600,
1560 cm-1 1H NMR (60 MHz, CCl4) δ 2.30 (s, 3H), 3.66 (s,
;
2H), 4.33 (brs, 2H), 6.46-6.82 (m, 2H), 6.96-7.59 (m, 6H).
Anal. Calcd for C16H15NS: C, 75.85; H, 5.97; N, 5.53. Found:
C, 75.91; H, 5.99; N. 5.48.
(35) (a) Vogel, A. I. A Text Book of Practical Organic Chemistry, 4th
ed.; ELBS, Longman Group Limited: London, 1978; pp 695-696. (b)
Barker, J . M.; Huddlestone, P. R.; Wood M. L. Synth. Commun. 1975,
5, 59-64. (c) Das, B.; Kundu, N. G. Synth. Commun. 1988, 855-867.
Tosyla te of 19: pale yellow gum; IR (liquid film) 3260, 1600,
1580 cm-1 1H NMR (60 MHz, CCl4) δ 2.33 (s, 6H), 3.36 (s,
;

4570 J . Org. Chem., Vol. 66, No. 13, 2001
Kundu and Nandi
2H), 6.82-7.39 (m, 8H), 7.53-7.85 (m, 4H), 7.92 (s, 1H). Anal.
Calcd for C23H21NO2S2: C, 67.78; H, 5.19; N, 3.44. Found: C,
67.54; H, 4.98; N, 3.26.
for C22H18N2S3: C, 64.99; H, 4.46; N, 6.88. Found: C, 65.21; H,
4.33; N, 6.75.
Tosyla te of 25: light brown gum; IR (liquid film) 3260,
1590, 1465 cm-1; 1H NMR (60 MHz, CCl4) δ 2.33 (s, 6H), 3.39
(s, 4H), 6.92-7.36 (m, 10H), 7.43-7.76 (m, 10H). Anal. Calcd
for C36H30N2O4S5: C, 60.47; H, 4.23; N, 3.91. Found: C, 60.66;
H, 4.17; N, 3.75.
3-(2-Am in op h e n ylt h io)-1-(4-m e t h ylp h e n yl)p r op -1-
yn e (20): light yellow oil; IR (liquid film) 3450, 3360, 1600,
1
1505, 1475 cm-1; H NMR (300 MHz, CDCl3) δ 2.33 (s, 3H),
3.65 (s, 2H), 4.38 (brs, 2H), 6.66-6.73 (m, 2H), 7.06 (d, J )
8.1 Hz, 2H), 7.13 (td, J ) 8.1, 1.5 Hz, 1H), 7.22 (d, J ) 8.1 Hz,
2H), 7.48 (dd, J ) 7.5, 1.2 Hz, 1H). 13C NMR (75 MHz, CDCl3)
δ 21.4, 24.1, 83.8, 84.7, 114.8, 116.6, 118.4, 120, 128.9, 130.5,
131.4, 137, 138, 148.8 13C NMR (75 MHz, CDCl3, DEPT 135)
δ 21.4, 24.1 (inverted), 114.8, 118.4, 128.8, 130.5, 131.4, 137.
Anal. Calcd for C16H15NS: C, 75.85; H, 5.97; N, 5.53. Found:
C, 75.60; H, 6.35; N, 5.28.
1,3-Bis[3-(2-am in oph en ylth io)pr op-1-yn yl]ben zen e (26):
light brown oil. IR (liquid film) 3450, 3340, 1600, 1580 cm-1
;
1H NMR (60 MHz, CCl4) δ 3.36 (s, 4H), 4.26 (brs, 4H), 6.50-
6.69 (m, 4H), 6.91-7.56 (m, 7H), 7.72 (s, 1H). Analysis could
not be performed since this compound was contaminated with
the starting material. These two compounds have the same
Rf value (TLC), so it could not be purified properly. In the
tosylation step, the disubstituted alkyne was separated from
the starting material.
Tosyla te of 20: white solid; mp 69 °C; IR 3280, 1597, 1575,
1
1520, 1470 cm-1; H NMR (300 MHz, CDCl3) δ 2.34 (s, 6H),
3.43 (s, 2H), 7.04-7.32 (m, 8H), 7.54 (dd, J ) 7.8, 1.2 Hz, 1H),
7.67 (d, J ) 8.1 Hz, 3H), 7.95 (s, 1H). 13C NMR (75 MHz,
CDCl3) δ 21.4, 25.7, 83.3, 84.9, 119.4, 120.1, 123.4, 124.7, 127.1,
128.9, 129.6, 130.5, 131.4, 136.4, 136.8, 138.3, 139.3, 143.7.
13C NMR (75 MHz, CDCl3, DEPT 135) δ 21.6, 25.9 (inverted),
120.3, 124.9, 127.3, 129.1, 129.7, 130.7, 131.6, 136.8. Anal.
Calcd for C23H21NO2S2: C, 67.78; H, 5.19; N, 3.44. Found: C,
67.49; H, 5.30; N, 3.25.
3-(2-Am in op h en ylt h io)-1-(4-m et h oxyp h en yl)p r op -1-
yn e (21): pale yellow solid; mp 58 °C; IR 3450, 3360, 1605,
1565, 1500 cm-1; 1H NMR (60 MHz, CCl4) δ 3.56 (s, 2H), 3.73
(s, 3H), 4.39 (brs, 2H), 6.46-6.86 (m, 2H), 6.96-7.56 (m, 6H).
Anal. Calcd for C16H15NOS: C, 71.34; H, 5.61; N, 5.20. Found:
C, 71.38; H, 5.76; N, 5.47.
Tosyla te of 21: white solid; mp 86 °C; IR 3265, 1600, 1585
cm-1. 1H NMR (60 MHz, CCl4) δ 2.33 (s, 3H), 3.36 (s, 2H), 3.72
(s, 3H), 6.62-6.82 (m, 2H), 6.92-7.43 (m, 6H), 7.49-7.79 (m,
4H), 7.82 (s, 1H). Anal. Calcd for C23H21NO3S2: C, 65.22; H,
4.99; N, 3.30. Found: C, 65.28; H, 4.97; N, 3.47.
3-(2-Am in oph en ylth io)-1-(2-car bom eth oxyph en yl)pr op-
1-yn e (22): light yellow oil; IR (liquid film) 3460, 3360, 1720,
1605, 1565 cm-1; 1H NMR (60 MHz, CCl4) δ 3.82 (s, 2H), 3.96
(s, 3H), 4.49 (brs, 2H), 6.63-6.82 (m, 2H), 7.03-7.66 (m, 4H),
7.82-8.1 (m, 2H). Anal. Calcd for C17H15NO2S: C, 68.66; H,
5.08; N, 4.7. Found: C, 68.79; H, 5.17; N, 4.61.
Tosyla te of 26: light yellow gum; IR (liquid film) 3270,
1595, 1582, 1545 cm-1; 1H NMR (60 MHz, CCl4) δ 2.33 (s, 6H),
3.39 (s, 4H), 6.95-7.33 (m, 10H), 7.43-7.59 (m, 9H), 7.76 (s,
1H), 7.92 (s, 2H). Anal. Calcd for C38H32N2O4S4: C, 64.38; H,
4.55; N, 3.95. Found: C, 64.11; H, 4.62; N, 4.08.
1,4-Bis[3-(2-am in oph en ylth io)pr op-1-yn yl]ben zen e (27):
white solid; mp 117 °C; IR 3420, 3300, 1600, 1560, 1470 cm-1
;
1H NMR (300 MHz, CDCl3) δ 3.67 (s, 4H), 4.44 (brs, 4H), 6.71-
6.77 (m, 4H), 7.11-7.24 (m, 6H), 7.50 (dd, J ) 7.8, 1.5 Hz,
2H). Anal. Calcd for C24H20N2S2: C, 71.96; H, 5.03; N, 6.99.
Found: C, 72.05; H, 4.98; N, 6.92.
Tosyla te of 27: white solid; mp 120 °C; IR 3220, 1595, 1580,
1540 cm-1; 1H NMR (300 MHz, CDCl3) δ 2.34 (s, 6H), 3.44 (s,
4H), 7.08 (td, J ) 6, 1.5 Hz, 2H), 7.17-7.26 (m, 8H), 7.34 (td,
J ) 6, 1.5 Hz, 2H), 7.54 (dd, J ) 7.8, 1.5 Hz, 2H), 7.66 (dd, J
) 8.1, 1.5 Hz, 6H), 7.94 (s, 2H). Anal. Calcd for C38H32N2O4S4:
C, 64.88; H, 4.55; N, 3.95. Found: C, 64.31; H, 4.59; N, 3.88.
Typ ica l P r oced u r e for th e Syn th esis of (E)-2-Styr yl-
3-tosylben zoth ia zolin e (28). The tosylate of the disubsti-
tuted alkyne 15 (0.3 g, 0.76 mmol) was refluxed with CuI
(0.057 g, 0.3 mmol, 40 mol %) and triethylamine (0.31 g, 30.6
mmol) in THF (10 mL) for 36 h in an argon atmosphere. After
removal of the solvent, the residue was treated with H2O and
extracted with CHCl3. The CHCl3 extracts were combined,
washed with H2O, and dried (anhyd Na2SO4). The solvent was
removed and the residue obtained was chromatographed on
silica gel (60-120 mesh), eluent being light petroleum (60-
80 °C)/ethyl acetate (95/5, V/V), furnishing the benzothiazoline
28 (0.2 g, 67%) as a white solid. This was crystallized from
CHCl3/light petroleum (60-80 °C); mp 154 °C; IR 1600, 1560,
Tosyla te of 22: yellow oil; IR (liquid film) 3270, 1720, 1609,
1570 cm-1 1H NMR (60 MHz, CCl4) δ 2.33 (s, 3H), 3.46 (s,
;
2H), 3.86 (s, 3H), 7.03-7.49 (m, 8H), 7.06-7.79 (m, 3H), 7.86-
8.00 (m, 2H). Anal. Calcd for C24H21NO4S2: C, 63.83; H, 4.68;
N, 3.10. Found: C, 63.77; H, 4.68; N, 3.17.
1
3-(2-Am in oph en ylth io)-1-(2-th ien yl)pr op-1-yn e (23): light
1480, 1450 cm-1; H NMR (300 MHz, CDCl3) δ 2.32 (s, 3H),
brown oil; IR (liquid film) 3470, 3370, 1607, 1480 cm-1
;
1H
6.20 (dd, J ) 15, 6 Hz, 1H), 6.25 (d, J ) 6 Hz, 1H), 6.69 (d, J
) 15 Hz, 1H), 7.02-7.30 (m, 10H), 7.46 (d, J ) 9 Hz, 2H),
7.72 (d, J ) 9 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 21.5, 68.9,
120.9, 122.6, 125.3, 125.6, 126.6, 126.9, 127.3, 128, 128.4,
129.3, 130.6, 132.5, 134.5, 136.9, 144.2; 13C NMR (75 MHz,
CDCl3, DEPT 135) δ 21.7, 69.2, 121.1, 122.8, 125.5, 126.9,
NMR (60 MHz, CCl4) δ 3.62 (s, 2H), 4.39 (brs, 2H), 6.49-7.26
(m, 5H), 7.33-7.49 (m, 2H). Anal. Calcd for C13H11NS2: C,
63.63; H, 4.52; N, 5.7. Found: C, 63.79; H, 4.66; N, 5.82.
Tosyla te of 23: white solid; mp 104 °C; IR 3250, 1595, 1575
cm-1 1H NMR (60 MHz, CCl4) δ 2.33 (s, 3H), 3.39 (s, 2H),
;
6.49-7.00 (m, 7H), 7.43-7.76 (m, 4H), 7.89 (s, 1H). Anal. Calcd
for C20H17NO2S3: C, 60.12; H, 4.28; N, 3.50. Found: C, 60.34;
H, 4.51; N, 3.32.
127.1, 127.6, 128.3, 128.6, 129.6, 130.9. Anal. Calcd for C22H19-
NO2S2: C, 67.15; H, 4.86; N, 3.56. Found: C, 67.46; H, 5.07; N,
3.58.
3-(2-Am in op h en ylt h io)-1-(2,4-d im et h oxyp yr im id in -5-
yl)p r op -1-yn e (24): light brown oil; IR (liquid film) 3450,
3360, 1590, 1545 cm-1; 1H NMR (60 MHz, CCl4) δ 3.62 (s, 2H),
4.00 (s, 3H), 4.06 (s, 3H), 4.49 (brs, 2H), 6.49-6.79 (m, 2H),
7.00-7.50 (m, 2H), 8.03 (s, 1H). Anal. Calcd for C15H15N3O3S:
C, 59.78; H, 5.01; N, 13.93. Found: C, 59.53; H, 4.81; N, 13.86.
Tosyla te of 24: white solid; mp 121 °C. IR 3220, 1595, 1565
cm-1; 1H NMR (60 MHz, CCl4) δ 2.33 (s, 3H), 3.46 (s, 2H), 3.92
(s, 3H), 4.09 (s, 3H), 6.92-7.33 (m, 4H), 7.43-7.76 (m, 4H),
7.79 (s, 1H), 8.06 (s, 1H). Anal. Calcd for C22H21N3O4S2: C,
58.00; H, 4.64; N, 9.22. Found: C, 53.73; H, 4.51; N, 9.07.
Syn th eses of Su bstitu ted Dia lk yn es 25-27. The sub-
stituted dialkynes were synthesized according to the same
procedure as for the disubstituted alkynes using diiodo aryl
compounds (12-14) instead of the aryl iodides.
Compounds 29-40 were synthesized according to the
procedure as for the synthesis of 28.
(E)-2-[2-(1-Naph th yl)vin yl]-3-tosylben zoth iazolin e (29):
white solid; mp 184 °C; IR 1600, 1460 cm-1 1H NMR (300
;
MHz, CDCl3) δ 2.35 (s, 3H), 6.24 (dd, J ) 15, 6 Hz, 1H), 6.37
(d, J ) 6 Hz, 1H), 7.06-7.18 (m, 5H), 7.36 (d, J ) 15 Hz, 1H),
7.45-7.53 (m, 6H), 7.72-7.81 (m, 3H), 7.99 (d, J ) 6 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ 22, 69.5, 121.4, 123.3, 124.1,
124.6, 125.8, 125.9, 126.2, 126.6, 127.5, 127.9, 128.4, 128.9,
129.9, 130., 131.6, 133.1., 133.7, 133.9, 135, 137.4, 144.9; 13C
NMR (75 MHz, CDCl3, DEPT 135) δ 21.8, 69.2, 121.1, 123,
123.8, 124.3, 125.5, 125.6, 125.9, 126.4, 127.2, 127.6, 128.1,
128.6, 129.7, 129.7. Anal. Calcd for C26H21NO2S2: C, 70.42; H,
4.77; N, 3.15. Found: C, 70.36; H, 4.71; N, 3.09.
(E)-2-[2-(2-Naph th yl)vin yl]-3-tosylben zoth iazolin e (30):
2,5-Bis[3-(2-a m in op h en ylt h io)p r op -1-yn yl]t h iop h en e
(25): light brown oil; IR (liquid film) 3460, 3360, 1590, 1475
white solid; mp 144 °C; IR 1590, 1445 cm-1 1H NMR (300
;
MHz, CDCl3) δ 2.34 (s, 3H), 6.32 (dd, J ) 15, 6 Hz, 1H), 6.36
(d, J ) 6 Hz, 1H), 6.87 (td, J ) 15, 3.6 Hz, 1H), 7.04-7.17 (m,
5H), 7.4-7.51 (m, 5H), 7.7-7.78 (m, 5H); 13C NMR (75 MHz,
1
cm-1; H NMR (60 MHz, CCl4) δ 3.59 (s, 4H), 4.26 (brs, 4H),
6.53-6.82 (m, 4H), 6.89 (s, 2H), 7.03-7.56 (m, 4H). Anal. Calcd

Pd-Cu-Catalyzed Synthesis of Benzofused Heterocycles
J . Org. Chem., Vol. 66, No. 13, 2001 4571
CDCl3) δ 22, 69.5, 121.4, 123.2, 124.1, 125.9, 126.5, 126.7,
127.5, 127.8, 127.9, 128, 128.5, 128.6, 129.9, 131.3, 133.1,
133.6, 133.6, 133.8, 134.9, 137.4, 144.9; 13C NMR (75 MHz,
CDCl3; DEPT 135) δ 21.7, 69.3, 121.1, 122.9, 123.8, 125.6,
126.3, 126.4, 127.2, 127.5, 127.6, 127.7, 128.2, 128.3, 129.7,
131.01. Anal. Calcd for C26H21NO2S2: C, 70.40; H, 4.77; N, 3.15.
Found: C, 70.36; H, 4.71; N, 3.09.
3.93 (2s, 6H), 6.15 (d, J ) 6 Hz, 1H), 6.29 (dd, J ) 15.6, 6 Hz,
1H), 6.56 (d, J ) 15.5 Hz, 1H), 6.95-7.09 (m, 6H), 7.4 (d, J )
8.1 Hz, 2H), 8.12 (s, 1H); Anal. Calcd for C22H21N3S2O4: C,
58.00; H, 4.64; N, 9.22. Found: C, 57.89; H, 4.51; N, 9.08.
2,5-B is [(E )-2-(3′-t o s y l-2′-b e n zo t h ia zo lin y l)v in y l]-
th iop h en e (38): light yellow solid; mp 112 °C; IR 1625, 1590,
1450 cm-1; 1H NMR (300 MHz, CDCl3) δ 2.34 (s, 6H), 5.91 (dd,
J ) 15, 6 Hz, 2H), 6.17 (d, J ) 6 Hz, 2H), 6.69-6.76 (m, 4H),
7.00-7.13 (m, 10H), 7.44 (d, J ) 8.1 Hz, 4H), 7.69 (d, J ) 7.8
Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 22, 69, 121.4, 123.2,
124.3, 125.9, 126.9, 127.5, 127.6, 127.8, 128.2, 129.9, 132.9,
134.9, 137.3, 140.8, 144.8; 13C NMR (75 MHz, CDCl3; DEPT
135) δ 21.7, 68.7, 121.1, 122.9, 124, 125.6, 126.6, 127.2, 127.4,
127.6, 127.9, 129.6. Anal. Calcd for C36H30N2O4S5: C, 60.47;
H, 4.23; N, 3.91. Found: C, 60.35; H, 4.22; N, 3.80.
(E)-2-[2-(m -Ch lor o)styr yl]-3-tosylben zoth ia zolin e (31):
1
white solid; mp 147 °C; IR 1595, 1560, 1460 cm-1; H NMR
(300 MHz, CDCl3) δ 2.36 (s, 3H), 6.17 (dd, J ) 15, 6 Hz, 1H),
6.24 (d, J ) 6 Hz, 1H), 6.64 (d, J ) 15 Hz, 1H), 7.02-7.18 (m,
8H), 7.31 (s, 1H), 7.47 (d, J ) 8.4 Hz, 2H), 7.73 (d, J ) 7.8 Hz,
1H). 13C NMR (75 MHz, CDCl3) δ 22, 69.1, 121.4, 123.2, 125.6,
125.9, 127.2, 127.5, 127.9, 128.6, 128.5, 129.8, 129.9, 130.1,
132.8, 134.9, 137.3, 138, 144.9; 13C NMR (75 MHz, CDCl3,
DEPT 135) δ 21.7, 68.8, 121.1, 122.9, 125.3, 125.7, 126.9, 127.2,
1,3-Bis[(E)-2-(3′-t osyl-2′-b en zot h ia zolin yl)vin yl]b en -
127.6, 128.3, 128.2, 129.5, 129.6, 129.8. Anal. Calcd for C22H18
-
zen e (39): white solid; mp 125 °C; IR 1600, 1550 cm-1 1H
;
ClNO2S2: C, 61.73; H, 4.24; N, 3.27. Found: C, 61.56; H, 4.18;
N, 3.03.
NMR (300 MHz, CDCl3) δ 2.35 (s, 6H), 6.18 (dd, J ) 15, 6 Hz,
2H), 6.24 (d, J ) 6 Hz, 2H), 6.6 (d, J ) 15 Hz, 2H), 6.99-7.4
(m, 13H), 7.46-7.54 (m, 4H), 7.67 (s, 1H), 7.73 (dd, J ) 7.5,
0.9 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 22, 69.1, 121.3, 123.2,
125.9 126.7, 127.5, 127.8, 128.5, 129.5, 129.9, 130.6, 132.8,
134.8, 136.1, 137.3, 137.3, 138.3, 145; 13C NMR (75 MHz,
CDCl3; DEPT 135) δ 21.8, 68.8, 121.1, 122.9, 125.7, 126.4,
127.3, 127.6, 128.2, 129.3, 129.7, 130.3, 135.7, 127.1. Anal.
Calcd for C38H32N2O4S4: C, 64.38; H, 4.55; N, 3.95. Found: C,
64.68; H, 4.69; N, 3.99.
1,4-Bis[(E)-2-(3′-t osyl-2′-b en zot h ia zolin yl)vin yl]b en -
zen e (40): white solid; mp 148-149 °C; IR 1595, 1570, 1550
cm-1; 1H NMR (300 MHz, CDCl3) δ 2.37 (s, 6H), 6.23 (dd, J )
15, 6 Hz, 2H), 6.27 (d, J ) 6 Hz, 2H), 6.65 (d, J ) 15 Hz, 2H),
7.05-7.15 (m, 10H), 7.5 (d, J ) 8.1 Hz, 4H), 7.60 (d, J ) 8.4
Hz, 4H), 7.75 (d, J ) 7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3)
δ 22.1, 69.2, 121.4, 123.2, 125.9, 127.6, 127.8, 127.9, 129.1, 130,
132.9, 134.7, 135.6, 137.3, 138, 145; 13C NMR (75 MHz, CDCl3;
DEPT 135) δ 21.8, 68.9, 121.1, 122.9, 125.6, 127.3, 127.7, 127.7,
128.8, 129.7, 137.7. Anal. Calcd for C38H32N2O4S4: C, 64.38;
H, 4.55; N, 3.95. Found: C, 64.08; H, 4.64; N, 3.95.
(E)-2-[2-(o-Tolyl)vin yl]-3-tosylben zoth iazolin e (32): white
solid; mp 86 °C; IR 1596, 1460 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 2.28 (s, 3H), 2.35 (s, 3H), 6.06 (dd, J ) 15, 6 Hz, 1H),
6.25 (d, J ) 6 Hz, 1H), 6.82 (d, J ) 15 Hz, 1H), 7.06-7.25 (m,
9H), 7.45 (d, J ) 9 Hz, 2H), 7.75 (d, J ) 9 Hz, 1H). Anal. Calcd
for C23H21NO2S2: C, 67.78; H, 5.19; N, 3.44. Found: C, 67.85;
H, 5.26; N, 3.61.
(E)-2-[2-(p-Tolyl)vin yl]-3-tosylben zoth iazolin e (33): white
solid; mp 109 °C; IR 1595, 1455, 1360 cm-1; 1H NMR (300 MHz,
CDCl3) δ 2.28 (s, 3H), 2.32 (s, 3H), 6.16 (dd, J ) 15, 6 Hz, 1H),
6.25 (d, J ) 6 Hz, 1H), 6.67 (d, J ) 15 Hz, 1H), 7.01-7.22 (m,
9H), 7.47 (d, J ) 9 Hz, 2H), 7.72 (d, J ) 9 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 21.2, 21.6, 69.2, 120.9, 122.7, 125.3, 125.7,
126.8, 127, 127.4, 129.2, 129.5, 130.6, 132.7, 132.8, 134.5,
136.9, 138, 144.4; 13C NMR 75 MHz, CDCl3, DEPT 135) 21.4,
21.7, 69.3, 121.1, 122.9, 125.5, 125.9, 127, 127.2, 127.6, 129.4,
129.6, 130.8. Anal. Calcd for C23H21NO2S2: C, 67.78; H, 5.19;
N, 3.44. Found: C, 67.87; H, 5.01; N, 3.13.
(E)-2-[2-(4-Meth oxyp h en yl)vin yl]-3-tosylben zoth ia zo-
lin e (34): white solid; mp 143 °C; IR 1600, 1570, 1500 cm-1
;
Typ ica l P r oced u r e for th e Syn th esis of 2-(2-P h en yl-
et h yl)-3-t osylb en zot h ia zolin e (42). (E)-2-(2-Phenylvinyl)-
3-tosylbenzothiazoline 28 (300 mg, 0.76 mmol) was hydroge-
nated in the presence of 10% Pd on activated charcoal (100
mg) in dry ethyl acetate (25 mL) at atmospheric pressure for
2 days (48 h.). After completion of the reaction, the catalyst
was removed by filtration and washed with ethyl acetate. The
solvent was distilled off, and the residue was chromatographed
on silica gel (60-120 mesh) with the eluent being light
petroleum/ethyl acetate (95/5, V/V) to afford 42 as a white
1H NMR (300 MHz, CDCl3) δ 2.35 (s, 3H), 3.76 (s, 3H), 6.07
(dd, J ) 15, 6 Hz, 1H), 6.23 (dd, J ) 6, 0.9 Hz, 1H), 6.65 (d, J
) 15 Hz, 1H), 6.79 (d, J ) 9 Hz, 2H), 7.02-7.14 (m, 5H), 7.26
(d, J ) 9 Hz, 2H), 7.47 (d, J ) 9 Hz, 2H), 7.72 (d, J ) 9 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 22, 55.6, 69.7, 114.3, 121.4,
123.1, 125, 125.8, 127.4, 127.8, 128.6, 129.9, 130.7, 133.2,
133.8, 135.1, 137.4, 144.8, 160.1; 13C NMR (75 MHz, CDCl3;
DEPT 135) δ 21.7, 55.3, 69.4, 114, 121.1, 122.8, 124.7, 125.5,
127.1, 127.6, 128.3, 129.6, 130.4. Anal. Calcd for C23H21NO3S2:
C, 65.22; H, 4.99; N, 3.3. Found: C, 65.41; H, 4.96; N, 3.19.
(E)-2-[2-(2-Car bom eth oxyph en yl)vin yl]-3-tosylben zoth i-
a zolin e (35): white solid; mp 153 °C; IR 1720, 1595 cm-1; 1H
NMR (300 MHz, CDCl3) δ 2.33 (s, 3H), 3.83 (s, 3H), 6.07 (dd,
J ) 15, 6 Hz, 1H), 6.26 (d, J ) 6 Hz, 1H), 7.00-7.13 (m, 5H),
7.23-7.51 (m, 6H), 7.71 (d, J ) 7.5 Hz, 1H), 7.97 (d, J ) 7.8
Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 22, 52.6, 69.4, 121.3,
123.1, 125.8, 127.8, 128, 128.1, 129.4, 129.6, 129.9, 130.4,
132.4, 133, 135, 137.4, 137.8, 144.8, 168; 13C NMR (75 MHz,
CDCl3; DEPT 135) δ 21.7, 52.2, 69.1, 121, 122.8, 125.5, 127.1,
127.7, 127.8, 129.3, 129.6, 130.1, 130.7, 132.1. Anal. Calcd for
solid; mp 130 °C; IR 1590, 1490 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 2.00-2.12 (m, 1H), 2.20-2.30 (m, 1H), 2.34 (s, 3H),
2.83 (t, J ) 7.5 Hz, 2H), 5.56 (t, J ) 6.9 Hz, 1H), 7.00-7.25
(m, 10H), 7.37 (d, J ) 8.1 Hz, 2H), 7.68 (d, J ) 7.5 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ 22, 31.7, 41.4, 69.2, 121.9, 122.9,
125.6, 126.5, 127.4, 127.9, 128.8, 128.9, 129.8, 134.2, 134.7,
137.3, 141, 144.7; 13C NMR (75 MHz, CDCl3; DEPT 135) δ 21.7,
31.5 (inverted), 41.1 (inverted), 68.9, 121.7, 122.7, 125.3, 126.2,
127.2, 127.6, 128.5, 128.6, 129.5. Anal. Calcd for C22H21NO2S2:
C, 66.80; H, 5.35; N, 3.54. Found: C, 66.69; H, 5.22; N, 3.47.
Similar procedure was followed for the synthesis of 43-47.
2-[2-(1-Na p h t h yl)et h yl]-3-t osylb en zot h ia zolin e (43):
C
24H21NO4S2: C, 63.83; H, 4.68; N, 3.10. Found: C, 63.67; H,
4.79; N, 3.19.
white solid; mp 162 °C; IR 1596.2, 1510.3, 1495.5 cm-1 1H
;
(E)-2-[2-(2-Th ien yl)vin yl]-3-tosylben zoth ia zolin e (36):
NMR (300 MHz, CDCl3) δ 2.15-2.26 (m, 1H), 2.30-2.41 (m,
4H), 3.21-3.38 (m, 2H), 5.70 (t, J ) 9 Hz, 1H), 7.04-7.14 (m,
5H), 7.36-7.47 (m, 6H), 7.68-7.84 (m, 3H), 8.01 (d, J ) 7.5
Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 22, 28.9, 40.7, 69.5, 122,
123, 124, 125.7, 125.9, 126, 126.4, 126.5, 127.3, 127.5, 127.9,
129.1, 129.8, 134.2, 134.3, 134.7, 137.2, 137.3, 144.8. 13C NMR
(75 MHz, CDCl3; DEPT 135) δ 21.8, 28.6 (inverted), 40.5
(inverted), 69.2, 121.7, 122.7, 123.7, 125.4, 125.6, 126.1, 126.2,
127, 127.2, 127.6, 128.9, 129.5. Anal. Calcd for C26H23NO2S2:
C, 70.08; H, 5.20; N, 3.14. Found: C, 69.95; H, 5.22; N, 3.17.
2-[2-(2-Na p h t h yl)et h yl]-3-t osylb en zot h ia zolin e (44):
1
white solid; mp 143 °C; IR 1625, 1590, 1490, 1450 cm-1; H
NMR (300 MHz, CDCl3) δ 2.33 (s, 3H), 6.02 (dd, J ) 15, 6 Hz,
1H), 6.22 (dd, J ) 6, 0.9 Hz, 1H), 6.81-6.94 (m, 3H), 7.00-
7.15 (m, 6H), 7.46 (d, J ) 8.4 Hz, 2H), 7.72 (d, J ) 7.8 Hz,
1H). 13C NMR (75 MHz, CDCl3) δ 22.1, 69.1, 121.4, 123.2,
124.5, 125.6, 125.9, 126.5, 127.5, 127.7, 127.9, 129.9, 133,
134.9, 137.3, 141, 144.9; 13C NMR (75 MHz, CDCl3; DEPT 135)
δ 21.8, 68.8, 121.1, 122.9, 124.2, 125.3, 125.6, 126.2, 127.2,
127.4, 127.6, 129.6. Anal. Calcd for C20H17NO2S3: C, 60.12; H,
4.29; N, 3.50. Found: C, 59.93; H, 4.40; N, 3.39.
(E)-2-[2-(2,4-Dim et h oxyp yr im id in -5-yl)vin yl]-3-t osyl-
ben zoth ia zolin e (37): white solid; mp 127 °C; IR 1590, 1550,
white solid; mp 123 °C; IR 1595, 1506.3, 1490.9, 1454.2 cm-1
;
1H NMR (300 MHz, CDCl3) δ 2.03-2.15 (m, 1H), 2.23-2.36
(m, 4H), 2.95 (t, J ) 9 Hz, 2H), 5.54 (t, J ) 9 Hz, 1H), 6.98-
1450 cm-1 1H NMR (300 MHz, CDCl3) δ 2.34 (s, 3H), 3.90,
;

4572 J . Org. Chem., Vol. 66, No. 13, 2001
Kundu and Nandi
7.06 (m, 5H), 7.27-7.37 (m, 5H), 7.58-7.70 (m, 5H); 13C NMR
(75 MHz, CDCl3) δ 22, 31.9, 41.3, 69.2, 122, 123, 125.6, 125.7,
126.3, 127, 127.5, 127.7, 128, 128.4, 129.8, 132.5, 134, 134.7,
137.3, 138.5, 144.7. 13C NMR (300 MHz, CDCl3, DEPT 135) δ
21.7, 31.6 (inverted), 40.9 (inverted), 69, 121.7, 122.7, 125.4,
126, 126.7, 127.2, 127.4, 127.6, 127.7, 128.1, 129.5. Anal. Calcd
for C26H23NO2S2: C, 70.08; H, 5.2; N, 3.14. Found: C, 70.1; H,
4.99; N, 3.15.
7.65-7.76 (m, 2H), 7.81-7.88 (m, 4H), 7.94 (s, 1H), 8.01 (d, J
) 8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 121.9, 122.7, 123.4,
123.6, 125.8, 126.7, 127.1, 127.3, 128.2, 128.8, 129.1, 129.2,
133.3, 133.9, 134.2, 138.2, 154.3. Anal. Calcd for C19H13NS: C,
79.41; H, 4.56; N, 4.87. Found: C, 79.6; H, 4.58; N, 4.88.
(E)-2-[2-(p-Tolyl)vin yl]ben zoth ia zole (51): light yellow
solid; mp 130 °C; IR 1625.9, 1602.7, 1569.9, 1515.9, 1479.3
1
cm-1; H NMR (300 MHz, CDCl3) δ 2.31 (s, 3H), 7.15 (d, J )
7.8 Hz, 2H), 7.24-7.49 (m, 6H), 7.79 (d, J ) 8.1 Hz, 1H), 7.92
(d, J ) 8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 30.1, 121.5,
121.9, 123.2, 125.6, 127.7, 129.8, 130.1, 133.1, 138.2, 140.1,
154.2, 167.9. Anal. Calcd for C16H13NS: C, 76.46; H, 5.21; N,
5.57. Found: C, 76.66; H, 5.27; N, 5.42.
2-(2-p-Tolyleth yl)-3-tosylben zoth azolin e (45): white solid;
1
mp 84 °C; IR 1600, 1580 cm-1; H NMR (300 MHz, CDCl3) δ
1.89-2.01 (m, 1H), 2.09-2.19 (m, 1H), 2.21 (s, 3H), 2.24 (s,
3H), 2.70 (t, J ) 7.8 Hz, 2H), 5.48 (t, J ) 7.2 Hz, 1H), 6.91-
7.07 (m, 9H), 7.29 (d, J ) 8.4 Hz, 2H), 7.61 (d, J ) 9 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ 21.4, 22, 31.3, 41.5, 69.3, 121.9,
123, 125.6, 127.4, 127.9, 128.8, 129.5, 129.8, 134.2, 134.8,
135.8, 137.3, 137.9, 144.7; 13C NMR (75 MHz, CDCl3) δ 21.1,
21.7, 31 (inverted), 41.3 (inverted), 69, 121.7, 122.7, 125.3,
127.2, 127.6, 128.5, 129.2, 129.5. Anal. Calcd for C23H23NO2S2:
C, 67.44; H, 5.66; N, 3.41. Found: C, 67.53; H; 5.36; N, 3.14.
2-[2-(4-Met h oxyp h en yl)et h yl]-3-t osylb en zot h ia zolin e
(46): colorless oil; IR (liquid film) 1596.7, 1580 cm-1; 1H NMR
(300 MHz, CDCl3) δ 1.94-1.99 (m, 1H), 2.09-2.19 (m, 1H),
2.27 (s, 3H), 2.70 (t, J ) 9 Hz, 2H), 3.70 (s, 3H), 5.48 (t, J ) 9
Hz, 1H), 6.74 (dd, J ) 6, 3 Hz, 2H), 6.95-7.08, (m, 7H), 7.3 (d,
J ) 9 Hz, 2H), 7.62 (dd, J ) 9, 3 Hz, 1H). Anal. Calcd for
(E)-2-[2-(4-Met h oxyp h en yl)vin yl]b en zot h ia zole (52):
white solid; mp 142 °C; IR 1625.9, 1602.7, 1575.7, 1514 cm-1
;
1H NMR (300 MHz, CDCl3) δ 3.85 (s, 3H), 6.93 (d, J ) 8.7 Hz,
2H), 7.24-7.38 (m, 2H), 7.43-7.54 (m, 4H), 7.84 (d, J ) 7.8
Hz, 1H), 7.97 (d, J ) 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3)
δ 55.7, 114.8, 120.3, 121.8, 123.1, 125.5, 126.6, 128.5, 129.3,
134.6, 137.8, 154.3, 161.1, 167.8. Anal. Calcd for C16H13NOS:
C, 71.88; H, 4.90; N, 5.23. Found: C, 72.10; H, 4.88; N, 5.31.
(E )-2 -[2 -(2 -C a r b o m e t h o x y p h e n y l )v i n y l ]b e n z o -
th ia zole (53): white solid; mp 110 °C; IR 1714.6, 1628.3, 1600,
1580.2, 1494.7 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.87 (s, 3H),
7.18-7.39 (m, 4H), 7.46 (t, J ) 7.5 Hz, 1H), 7.65 (d, J ) 7.8
Hz, 1H), 7.75 (d, J ) 7.8 Hz, 1H), 7.90 (d, J ) 8.1 Hz, 2H),
8.33 (d, J ) 15 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 51.2,
120.4, 122.1, 123.8, 124.4, 125.2, 126.2, 127.6, 127.8, 129.9,
131.4, 135.7, 136.2, 152.8, 166.1. Anal. Calcd for C17H13NO2S:
C, 69.13; H, 4.43; N, 4.74. Found: C, 69.06; H, 4.35; N, 4.79.
1,3-Bis[(E)-2-(2′-ben zoth ia zolyl)vin yl]ben zen e (54): pale
C
23H23NO3S2: C, 64.91; H, 5.44; N, 3.29. Found: C, 64.87; H,
5.43; N, 3.31.
2-[2-(2-Ca r bom eth oxyp h en yl)eth yl]-3-tosylben zoth ia -
zolin e (47): white solid; mp 79 °C; IR 1716.5, 1595.2 cm-1
.
1H NMR (300 MHz, CDCl3) δ 1.98-2.17 (m, 2H), 2.28 (s, 3H),
3.09 (t, J ) 9 Hz, 2H), 3.79 (s, 3H), 5.56 (t, J ) 9 Hz, 1H),
6.95-7.05 (m, 5H), 7.16-7.21 (m, 2H), 7.30-7.35 (m, 3H), 7.63
(d, J ) 7.5 Hz, 1H), 7.79 (d, J ) 7.8 Hz, 1H); 13C NMR (75
MHz, CDCl3) δ 22.03, 30.9, 41.6, 52.4, 69.5, 121.9, 122.9, 125.5,
126.6, 127.4, 127.8, 129.8, 129.9, 131.3, 131.5, 132.5, 134.3,
134.8, 137.3, 143, 144.7, 168.3. 13C NMR (75 MHz, CDCl3;
DEPT 135) δ 21.7, 30.6 (inverted), 41.3 (inverted), 52.1, 69.2,
121.6, 122.6, 125.3, 126.3, 127.1, 127.6, 129.5, 131, 131.2,
132.2. Anal. Calcd for C24H23NO4S2: C, 63.55; H, 5.11; N, 3.08.
Found: C, 63.76; H, 4.98; N, 3.24.
yellow solid; mp 120 °C; IR 1625.9, 1583.4, 1554.5, 1485.1 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.14 (t, J ) 7.8 Hz, 2H), 7.36-
7.55 (m, 7H), 7.68 (d, J ) 7.5 Hz, 2H), 7.87 (d, J ) 7.2 Hz,
2H), 7.93 (s, 1H), 8.00 (d, J ) 8.1 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 121.9, 123.5, 123.7, 125.9, 126.8, 126.8, 130.9, 136,
136.7, 138, 138.5, 154.2, 166.6. Anal. Calcd for C24H16N2S2: C,
72.69; H, 4.07; N, 7.06. Found: C, 72.58; H, 4.11; N, 7.13.
(E)-2-[2-(Ur a cil-5-yl)vin yl]-3-tosylben zoth ia zolin e (55).
Compound 37 (70 mg, 0.15 mmol) in acetonitrile (3 mL) was
stirred with anhydrous sodium iodide (70 mg, 0.46 mmol) and
chlorotrimethylsilane (50 mg, 0.46 mmol) at room temperature
for 24 h in an argon atmosphere. After removal of solvent
under reduced pressure the residue was treated with saturated
sodium metabisulfite solution (0.5 mL) and then with water
(2 mL). This was filtered and dried to yield a pale yellow solid
which was crystallized from MeOH-H2O to afford a white
solid; mp >250 °C. IR 3242.1, 3184.2, 1712.7, 1678, 1596.9
cm-1. 1H NMR (300 MHz, DMSO-d6 ) δ 2.34 (s, 3H), 6.20 (d, J
) 6 Hz, 1H), 6.33 (dd, J ) 15.6, 6 Hz, 1H), 6.60 (d, J ) 15.6
Hz, 1H), 7.00-7.14 (m, 6H), 7.44 (d, J ) 8.1 Hz, 2H), 8.16 (s,
Typ ica l P r oced u r e for th e Syn th esis of (E)-2-(2-P h en -
ylvin yl)ben zoth ia zole (48). (E)-2-(2-Phenylvinyl)-3-tosyl-
benzothiazoline 28 (180 mg, 0.46 mmol) was added to KOBut
(made from K ) 60 mg, 1.38 mmol) in dry DMF (5 mL) at 0
°C. This reaction mixture was stirred at room temperature for
3 h. Ethyl acetate (10 mL) and saturated NaCl solution (5 mL)
were added, and ethyl acetate layer was separated. The
aqueous layer was further extracted with ethyl acetate. The
combined organic layer was washed with H2O and dried over
anhyd Na2SO4. After removal of the solvent under reduced
pressure, a light brown solid was obtained which on crystal-
lization [CHCl3/petroleum spirit (60-80 °C)] afforded 48 as a
1H), 11.14 (s, 1H), 11.35 (s, 1H). Anal. Calcd for C20H17
-
N3S2O4: C, 56.19; H, 4.00; N, 9.82. Found: C, 57.95; H, 3.98;
N, 9.71.
white solid; mp 112 °C (lit36 mp: 112 °C); IR 1625, 1480 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.34-7.47 (m, 7H), 7.53 (dd, J
) 9, 3 Hz, 2H), 7.82 (d, J ) 7.8 Hz, 1H), 7.99 (d, J ) 7.8 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 121.9, 122.5, 123.4, 125.7,
Con ver sion of (E)-2-[2-(m -Ch lor op h en yl)vin yl]-3-tos-
ylben zoth ia zolin e 31 to m -Ch lor ocin n a m a ld eh yd e. To a
DMF solution (25 mL) of (E)-2-[2-(m-chlorophenyl)vinyl]-3-
tosylbenzothiazoline 31 (280 mg, 0.65 mmol) was added
phosphate buffer (0.05 M, pH ) 7, 2 mL) at room temperature
followed by the addition of AgNO3 solution (180 mg, 1.05 mmol
in 1.75 mL of H2O). After a few minutes, a curdy white
precipitate appeared and more AgNO3 solution (180 mg, 1.05
mmol in 1.75 mL H2O) was added. After stirring the reaction
mixture for 10 min, Et3N (71 mg, 0.0.7 mmol) was added and
stirred for 2 h. The reaction mixture was filtered through
Celite bed and washed throughly with ether. The ether layer
was washed with H2O and dried (anhydrous Na2SO4), and the
solvent was removed. A light yellow oil, m-chlorocinnamalde-
hyde, (80 mg, 73%) was obtained after purification through
neutral alumina (eluent being light petroleum/ethyl acetate:
80/20, V/V);yield: 80 mg, 73.29%. IR (liquid film) 1675, 1630,
126.7, 127.8, 129.3, 129.8, 134.7, 135.8, 138, 154.3, 167.2; 13
C
NMR (75 MHz, CDCl3; DEPT 135) δ 121.6, 122.2, 123.1, 125.4,
126.4, 127.5, 129, 129.5, 137.7. Anal. Calcd for C15H11NS: C,
75.91; H, 4.67; N, 5.90. Found: C, 75.82; H, 4.59; N, 5.77.
Compounds 49-54 were synthesized by following the above
procedure for 48.
(E)-2-[2-(1-Na p h t h yl)vin yl]b en zot h ia zole (49): white
1
solid; mp 116 °C; IR 1618.2, 1583.4, 1554.5, 1485.1 cm-1; H
NMR (300 MHz, CDCl3) δ 7.39 (t, J ) 7.8 Hz,1H), 7.45-7.62
(m, 6H), 7.84-7.96 (m, 4H), 8.03 (d, J ) 8.1 Hz, 1H), 8.26 (d,
J ) 8.1 Hz, 1H). Anal. Calcd for C19H13NS: C, 79.41; H, 4.56;
N, 4.87. Found: C, 79.68; H, 4.50; N, 4.86.
(E)-2-[2-(2-Na p h t h yl)vin yl]b en zot h ia zole (50): white
solid; mp 160 °C; IR 1620.5, 1582, 1550.5 cm-1; 1H NMR (300
MHz, CDCl3) δ 7.37 (t, J ) 7.5 Hz, 1H), 7.45-7.54 (m, 4H),
1
1600, 1560 cm-1; H NMR (300 MHz, CDCl3) δ 6.60 (dd, J )
15.9, 7.5 Hz, 1H), 7.28-7.44 (m, 5H), 8.61 (d, J ) 7.5 Hz, 1H).
Anal. Calcd for C9H7ClO: C, 64.86; H, 4.23. Found: C, 64.62;
H, 4.18.
(36) Brown, D. M.; Kon, G. A. R. J . Chem. Soc. 1948, 70, 2147-
2154.

Pd-Cu-Catalyzed Synthesis of Benzofused Heterocycles
J . Org. Chem., Vol. 66, No. 13, 2001 4573
S-(2-Am in op h en yl)-N,N-d im eth ylth ioca r ba m a te (57).
To a mechanically stirred solution of S-(2-Nitrophenyl)-N,N-
dimethylthiocarbamate30 56 (5.8 g, 27.3 mmol) in a mixture
of glacial acetic acid (60 mL) and water (20 mL), iron powder
(8 g, 136.5 mmol) was added slowly under ice-cold bath, and
the reaction mixture was then stirred at room temperature
for 8 h. This was neutralized with solid NaHCO3 and filtered
through a sintered-bed funnel, and the filtrate was extracted
with CHCl3. The organic layer was washed with H2O and dried
(anhyd Na2SO4), and the solvent was distilled off. The crude
compound obtained was purified by column chromatography
on silica gel (60-120 mesh) with the eluent being light
petroleum/ethyl acetate (80/20, V/V) to yield 57 as a light
yellow oil in 89% yield (4.47 g); IR (liquid film) 3442.7, 3334.7,
1660.6, 1614.3, 1587.3 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.01
(s, 3H), 3.12 (s, 3H), 3.75 (brs, 2H), 6.69-6.76 (m, 2H), 7.19
(dd, J ) 7.5, 1.8 Hz, 1H), 7.28 (dd, J ) 7.8, 1.5 Hz, 1H). Anal.
Calcd for C9H12N2OS: C, 55.07; H; 6.16; N, 14.26. Found: C,
54.88; H, 5.96; N, 14.51.
127.8, 128, 128.6, 131.7, 131.9, 138.3. Anal. Calcd for C22H20N2-
OS: C, 73.30; H, 5.59; N, 7.76. Found: C, 73.16; H, 5.49; N,
7.85.
S-[2-{N-3′-(2-Naph th yl)pr op-2′-yn yl}am in oph en yl]-N,N-
d im eth ylth ioca r ba m a te (59c): white solid; mp 104 °C; IR
3347.4, 1667.9, 1591.1, 1504.2 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 3.00, 3.12 (2s, 6H), 4.25 (s, 2H), 5.03 (brs, 1H), 6.78
(td, J ) 7.8, 0.9 Hz, 1H), 6.90 (dd, J ) 7.8, 0.9 Hz, 1H), 7.34-
7.47 (m, 5H), 7.72-7.49 (m, 3H), 7.92 (s, 1H); 13C NMR (75
MHz, CDCl3) δ 34.4, 37, 83.5, 86.4, 111.6, 112.3, 118.1, 120.1,
126.4, 126.5, 127.6, 127.8, 128.4, 131.5, 131.7, 132.7, 132.8,
138.1, 149.2, 165.8; 13C NMR (75 MHz, CDCl3, DEPT 135) δ
34.6 (inverted), 37.2, 111.8, 118.3, 126.6, 126.7, 127.8, 128,
128.6, 131.7, 131.9, 138.3. Anal. Calcd for C22H20N2OS: C,
73.30; H, 5.59; N, 7.76. Found: C, 73.21; H, 5.63; N, 7.81.
S-[2-(N-3′-m -ch lor op h en yl-p r op -2′-yn yl)a m in op h en yl]-
N,N-d im eth ylth ioca r ba m a te (59d ): white solid; mp 117 °C;
IR 3346.3, 1668.3, 1587.3, 1500 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 2.97, 3.12 (2s, 6H), 4.18 (s, 2H), 4.96 (brs, 1H), 6.79
(td, J ) 7.5, 1.2 Hz, 1H), 6.84 (d, J ) 7.8 Hz, 1H), 7.17-7.38
(m, 6H); 13C NMR (75 MHz, CDCl3) δ 34.7, 37.4, 82.3, 87.94,
112, 112.9, 118.6, 125, 129, 129.8, 130.3, 132.1, 134.5, 138.8,
149.5, 166.1; 13C NMR (75 MHz, CDCl3, DEPT 135) δ 34.4
(inverted), 37.2 111.8, 118.4, 128.6, 129.5, 130 131.8, 138.3.
Anal. Calcd for C18H17ClN2OS: C, 62.68; H, 4.97, N, 8.12.
Found: C, 62.76; H, 5.09; N, 7.91.
S-[2-(N-P r op -2′-yn yl)a m in op h en yl]-N,N-d im eth ylth io-
ca r ba m a te (58). Compound 57 (1 g, 5.09 mmol) was stirred
at room temperature with K2CO3 (0.7 g, 5.09 mmol) in acetone
(20 mL) in an argon atmosphere for 5 h. Propargyl bromide
(0.6 g, 5.09 mmol) was added slowly, and the reaction mixture
was heated under reflux for 16 h. Solvent was removed under
reduced pressure, and the residue was diluted with H2O. This
was extracted with CHCl3, washed with H2O, and dried (anhyd
Na2SO4). The residue obtained after removal of solvent was
purified by column chromatography on silica gel (60-120
mesh), using light petroleum/ethyl acetate (80/20, V/V) as
eluent to yield 58 as a white solid (0.8 g, 84%), mp 127 °C. IR
S-[2-(N-3′-o-Tolylp r op -2′-yn yl)a m in op h en yl]-N,N-d i-
m eth ylth ioca r ba m a te (59e): pale yellow solid; mp 88 °C; IR
1
3350.2, 1671.9, 1616, 1590 cm-1; H NMR (300 MHz, CDCl3)
δ 2.33 (s, 3H), 2.95, 3.12 (2s, 6H), 4.16 (s, 2H), 5.01 (brs, 1H),
6.73 (t, J ) 7.5 Hz, 1H), 6.78 (d, J ) 7.8 Hz, 1H), 7.08-7.35
(m, 5H), 7.49 (d, J ) 7.8 Hz, 1H). Anal. Calcd for C19H20N2OS:
C, 70.34; H, 6.21; N, 8.63. Found: C, 70.56; H, 5.99; N, 8.42.
S-[2-(N-3′-p-Tolylprop-2′-ynyl)aminophenyl]-N,N-dimeth-
ylthiocarbamate (59f): white solid; mp 100 °C; IR 3355.9,
1672.2, 1618, 1591 cm-1; 1H NMR (300 MHz, CDCl3) δ 2.32
(s, 3H), 3.00, 3.13 (2s, 6H), 4.17 (s, 2H), 4.95 (brs, 1H), 6.74
(td, J ) 7.8, 1.2 Hz, 1H), 6.82 (dd, J ) 7.8, 0.9 Hz, 1H), 7.06
(d, J ) 7.8 Hz, 2H), 7.24-7.36 (m, 4H); 13C NMR (75 MHz,
CDCl3) δ 21.9, 34.8, 37.4, 83.8, 85.7, 112.1, 112.6, 118.4, 120.3,
129.3, 132.1, 138.5, 149.6, 166.2; 13C NMR (75 MHz, CDCl3,
DEPT 135) δ 21.6, 34.5 (inverted), 37.1, 111.8, 118.1, 129.1,
131.7, 138.2. Anal. Calcd for C19H20N2OS: C, 70.34; H, 6.21;
N, 8.63. Found: C, 70.41; H, 6.18; N, 8.55.
S -[2-{N -3′-(4-Me t h o x y p h e n y l)p r o p -2′-y n y l}a m in o -
p h en yl]-N,N-d im eth ylth ioca r ba m a te (59g): white solid;
mp 85 °C; IR 3371, 1664, 1591, 1510 cm-1; 1H NMR (300 MHz,
CDCl3) δ 3.00, 3.12 (2s, 6H), 3.78 (s, 3H), 4.17 (s, 2H), 6.72-
6.85 (m, 4H), 7.27-7.36 (m, 4H). Anal. Calcd for C19H20N2O2S:
C, 67.03; H, 5.92; N, 8.22. Found: C, 66.89; H, 6.03; N, 8.19.
S-[2-{N-3′-(2-Th ien yl)p r op -2′-yn yl)a m in op h en yl]-N,N-
d im eth ylth ioca r ba m a te (59h ): white solid; mp 103 °C; IR
3348.5, 1668.3, 1510.8, 1504.8 cm-1; 1H NMR (60 MHz, CCl4)
δ 3.00 (s, 6H), 4.25 (s, 2H), 5.01 (brs, 1H), 6.66-6.89 (m, 3H),
7.03-7.43 (m, 4H). Anal. Calcd for C16H16N2OS2: C, 60.73; H,
5.09; N, 8.85. Found: C, 60.91; H, 4.99; N, 8.68.
1
3374, 3277, 1667.7, 1592.6 cm-1; H NMR (300 MHz, CDCl3)
δ 2.19 (t, J ) 3 Hz, 1H), 3.00, 3.12 (2s, 6H), 3.96 (d, J ) 3 Hz,
2H), 4.81 (brs, 1H), 6.72-6.79 (m, 2H), 7.30-7.35 (m, 2H); 13
C
NMR (75 MHz, CDCl3) δ 33.8, 37.4, 81, 96.5, 111.9, 112.8,
118.6, 132.1, 138.5, 149.3, 166; 13C NMR (75 MHz, CDCl3) δ
33.5 (inverted), 37.1, 80.8, 111.6, 118.3, 131.8, 138.2. Anal.
Calcd for C12H14N2OS: C, 61.51; H, 6.02; N, 11.95. Found: C,
61.77; H, 5.71; N, 12.00.
Typ ica l P r oced u r e for th e Syn th esis of S-[2-(N-3′-
P h en ylp r op -2′-yn yl)a m in op h en yl]-N,N-d im eth ylth ioca r -
ba m a te (59a ). A mixture of 58 (300 mg, 1.27 mmol), iodo-
benzene (340 mg, 1.65 mmol), (PPh3)2PdCl2 (30 mg, 0.43 mmol,
3.38 mol), copper(I) iodide (15 mg, 0.076 mmol, 6 mol %), and
triethylamine (610 mg, 5.08 mmol) in acetonitrile (5 mL) was
stirred at room temperature for 24 h in an argon atmosphere.
Solvent was removed under reduced pressure, and the residue
was diluted with H2O. This was extracted with CHCl3, and
the organic layer was washed with H2O. This was dried (anhyd
Na2SO4), and the solvent was removed to furnish a brown gum
which was purified by column chromatography on silica gel
(60-120 mesh) using light petroleum/ethyl acetate (80/20, V/V)
as eluent to yield 59a as a pale yellow oil. IR (liquid film)
3338.3, 1666.2, 1590.4, 1567.7 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 2.97, 3.09 (2s, 6H), 4.18 (s, 2H), 4.98 (brs, 1H), 6.75
(t, J ) 7.5 Hz, 1H), 6.84 (d, J ) 7.5 Hz, 1H), 7.22-7.26 (m,
3H), 7.34-7.4 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 34.8, 37.4,
83.7, 86.6, 112.1, 112.8, 118.5, 123.3, 128.7, 132.1, 138.3, 149.6,
166.2. 13C NMR (75 MHz, CDCl3, DEPT 135) δ 34.5 (inverted),
37.2 111.8, 118.2, 128.4, 131.9, 138.2. Anal. Calcd for C18H18N2-
OS: C, 69.65; H, 5.84; N, 9.02. Found: C, 69.81; H, 5.66; N,
8.97.
S-[2-{N-3′-(5-Iodo-2-th ien yl)pr op-2′-yn yl)}am in oph en yl]-
N,N-d im eth ylth ioca r ba m a te (59i): light yellow solid; mp
1
113 °C; IR 3346.3, 1666.4, 1591.2, 1502.4 cm-1; H NMR (60
MHz, CCl4) δ 3.06 (s, 6H), 4.26 (s, 2H), 4.89 (brs, 1H), 6.6-
6.85 (m, 3H), 7.03-7.49 (m, 3H). Anal. Calcd for C16H15IN2S2:
C, 43.44; H, 3.41; N, 6.33. Found: C, 43.49; N, 3.65; N, 6.08.
S-[2-{N-3′-(4-Iod op h en yl)p r op -2′-yn yl)}a m in op h en yl]-
N,N-d im eth ylth ioca r ba m a te (59j): white solid; mp 127 °C;
Compounds 59b-k were synthesized by following the
procedure for 59a .
IR 3390.6, 1668.3, 1591.2, 1500.5 cm-1 1H NMR (60 MHz,
;
S-[2-{N-3′-(1-Naph th yl)pr op-2′-yn yl}am in oph en yl]-N,N-
d im eth ylth ioca r ba m a te (59b): white solid; mp 84 °C; IR
3347.4, 1667.9, 1591.1 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.00,
3.12 (2s, 6H), 4.25 (s, 2H), 5.03 (brs, 1H), 6.78 (t, J ) 7.5 Hz,
1H), 6.93 (d, J ) 7.8 Hz, 1H), 7.30-7.48 (m, 5H), 7.59 (d, J )
7.2 Hz, 1H), 7.75 (t, J ) 7.5 Hz, 2H), 8.19 (d, J ) 7 Hz, 1H).
13C NMR (75 MHz, CDCl3) δ 34.4, 37, 83.5, 86.4, 111.6, 112.3,
118.1, 120.1, 126.4, 126.5, 127.6, 127.8, 128.85, 131.5, 131.7,
132.7, 132.8, 138.1, 149.1, 165.8. 13C NMR (75 MHz, CDCl3,
DEPT 135) δ 34.6 (inverted), 37.2 111.8, 118.3, 126.6, 126.7,
CCl4) δ 3.03 (s, 6H), 4.16 (s, 2H), 4.86 (brs, 1H), 6.66-6.86 (m,
2H), 7.06-7.39 (m, 4H), 7.56-7.22 (m, 2H). Anal. Calcd for
C
18H17IN2OS: C, 49.55; H, 3.92; N, 6.41. Found: C, 49.76; H,
3.79; N, 6.62.
S-[2-{N-3′-(2-Iod op h en yl)p r op -2′-yn yl)}a m in op h en yl]-
N,N-d im eth ylth ioca r ba m a te (59k ): white solid; mp 87 °C;
1
IR 3391.3, 1667.39, 1590.8, 1501.2 cm-1; H NMR (60 MHz,
CCl4) δ 3.09 (s, 6H), 4.2 (s, 2H), 5.00 (brs, 1H), 6.59-7.03 (m,
3H), 7.13-7.33 (m, 3H), 7.59-7.76 (m, 2H). Anal. Calcd for

4574 J . Org. Chem., Vol. 66, No. 13, 2001
Kundu and Nandi
C18H17IN2OS: C, 49.55; H, 3.92; N, 6.41. Found: C, 49.59; H,
3.85; N, 6.36.
148.5; 13C NMR (75 MHz, CDCl3 + DMSO-d6) δ 54.6 (inverted),
121.2, 124.2, 126.2, 130.9, 131.2, 132, 132.3, 132.4, 132.6,
132.9; Anal. Calcd for C19H15NS: C, 78.85; H, 5.22; N, 4.83.
Found: C, 79.00; H, 4.96; N, 4.69.
S-[2-(N-Meth yl-N-3′-p-tolyl-p r op -2′-yn yl)a m in op h en yl]-
N,N-d im eth ylth ioca r ba m a te (60a ). A mixture of compound
59f (100 mg, 0.3 mmol), anhyd K2CO3 (83 mg, 0.6 mmol), and
methyl iodide (130 mg, 0.91 mmol) in acetone (10 mL) was
treated under reflux for 10 h in an argon atmosphere. After
usual workup, the crude product was purified by column
chromatography on silica gel (60-120 mesh) using light
petroleum/ethyl acetate mixture (95/5, V/V) as eluent affording
(E)-2-[(m -Ch lor op h en yl)m eth ylid en e]-3,4-d ih yd r o-2H-
1,4-ben zoth ia zin e (61d ): white solid; mp 138 °C; IR 3383.9,
1611.5, 1585.9, 1555.3 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.86
(s, 2H), 4.09 (brs, 1H), 6.20 (s, 1H), 6.56 (dd, J ) 7.8, 1.2 Hz,
1H), 6.70 (td, J ) 7.5, 1.2 Hz, 1H), 6.89 (td, J ) 7.5, 1.2 Hz,
1H), 7.04 (dd, J ) 7.8, 1.2 Hz, 1H), 7.09-7.13 (m, 1H), 7.20 (t,
J ) 7.5 Hz, 1H), 7.32 (dd, J ) 7.8, 1.2 Hz, 1H), 7.14 (s, 1H);
13C NMR (75 MHz, CDCl3) δ 50 (3J CH ) 7.5 Hz), 116.5, 118.3,
120.2, 120.5, 126, 126.4, 126.9, 128.7, 129.6, 133.4, 134.2, 138,
143.9; 13C NMR (75 MHz, CDCl3, DEPT 135) δ 50.1 (inverted),
116.6, 120.3, 120.6, 126.1, 126.5, 127, 128.8, 129.7. Anal. Calcd
for C15H12ClNS: C, 65.79; H, 4.41; N, 5.11. Found: C, 66.06;
H, 4.47; N, 5.01.
60a as a colorless oil; IR (liquid film) 1673, 1583, 1509 cm-1
;
1H NMR (60 MHz, CCl4) δ 2.30 (s, 3H), 2.89 (s, 3H), 3.00 (s,
6H), 4.00 (s, 2H), 6.95-7.13 (m, 3H), 7.23-7.56 (m, 5H). Anal.
Calcd for C20H22N2OS: C, 70.97; H, 6.55; N, 8.27. Found: C,
70.89; H, 6.50; N, 8.16.
S-[2-(N-Ben zyl-N-3′-p-tolyl-p r op -2′-yn yl)a m in op h en yl]-
N,N-d im eth ylth ioca r ba m a te (60b): compound 59f (200 mg,
0.6 mmol) and PhCH2Br (120 mg, 0.7 mmol) were refluxed
with anhyd K2CO3 (165 mg, 1.2 mmol) for 15 h. After usual
workup, the crude product was purified by column chroma-
tography on silica gel (60-120 mesh) the eluent being light
petroleum/ethyl acetate (90/10, V/V) furnishing 60b as a
(E)-2-(o-Tolylm eth ylid en e)-3,4-d ih yd r o-2H-1,4-ben zo-
th ia zin e (61e): white solid; mp 124 °C; IR 3360.1, 1609.8,
1587.8, 1482.9 cm-1; 1H NMR (300 MHz, CDCl3) δ 2.21 (s, 3H),
3.89 (s, 2H), 6.34 (s, 1H), 6.53 (dd, J ) 7.5, 0.9 Hz, 1H), 6.65
(td, J ) 7.5, 0.9 Hz, 1H), 6.85 (td, J ) 7.2, 1.2 Hz, 1H), 6.94
(dd, J ) 7.8, 1.2 Hz, 1H), 7.09-7.17 (m, 3H), 7.45 (d, J ) 7.2
Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 19.9, 49.4 (3J CH ) 7.5
Hz), 116.3, 118.8, 120, 120.5, 125.5, 125.6, 126.2, 127.4, 128.6,
130.1, 132.3, 134.9, 136.3, 143.7; 13C NMR (75 MHz, CDCl3,
DEPT 135) δ 20.1, 49.6 (inverted), 116.5, 120.2, 120.7, 125.9,
125.8, 126.4, 127.6, 128.8, 130.3. Anal. Calcd for C16H15NS: C,
75.85; H, 5.97; N, 5.52. Found: C, 75.78; H, 5.83; N, 5.63.
(E)-2-(p-Tolylm eth ylid en e)-3,4-d ih yd r o-2H-1,4-ben zo-
th ia zin e (61f): white solid; mp 206 °C; IR 3362.8, 1584.1,
colorless oil; IR (liquid film) 1667.5, 1584.1, 1509 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 2.33 (s, 3H), 3.02 (s, 6H), 3.72 (s,
2H), 4.28 (s, 2H), 6.72 (t, J ) 6 Hz, 1H), 6.8 (d, J ) 6 Hz, 1H),
7.1-7.44 (m, 10H), 7.5 (d, J ) 9 Hz, 1H). Anal. Calcd for
C
26H26N2OS: C, 75.33; H, 6.32; N, 6.75. Found: C,75.28;H, 6.29;
N, 6.74.
Typ ica l Rea ction P r oced u r e for th e Syn th esis of (E)-
2-Ben zylid en e-3,4-d ih yd r o-2H-1,4-ben zoth ia zin e (61a ). A
methanolic KOH solution [KOH (360 mg, 6.5 mmol) dissolved
in 10 mL of methanol and 5 mL of H2O] of compound 59a (200
mg, 0.65 mmol) was heated under reflux in an argon atmo-
sphere for 24 h. The solvent was removed under reduced
pressure and diluted with water followed by extraction with
CHCl3. The organic layer was washed with H2O and dried
(anhyd Na2SO4), and the solvent was distilled off. The crude
product obtained was purified by column chromatography on
silica gel (60-120 mesh), the eluent being light petroleum/
ethyl acetate (19/1, V/V) to yield 61a as a white solid; mp 148
°C; IR 3382.9, 1608.5, 1585.4, 1487 cm-1; 1H NMR (300 MHz,
CDCl3) δ 3.94 (s, 2H), 6.36 (s, 1H), 6.61 (dd, J ) 8.1, 1.2 Hz,
1H), 6.76 (td, J ) 8, 1.2 Hz, 1H), 6.94 (td, J ) 7.5, 1.5 Hz,
1H), 7.10 (dd, J ) 7.8, 1.2 Hz, 1H), 7.22 (t, J ) 7.5 Hz, 1H),
7.36 (t, J ) 7.5 Hz, 2H), 7.50 (d, J ) 7.5 Hz, 2H); 13C NMR (75
MHz, CDCl3) δ 50.4 (3J CH ) 7.5 Hz) 116.8, 119.1, 120.5, 122.4,
126.1, 126.7, 127.3, 129, 129.5, 131.8, 136.6, 144.3; 13C NMR
(75 MHz, CDCl3, DEPT 135) δ 50.1 (inverted), 116.5, 120.2,
1
1492.7 cm-1; H NMR (300 MHz, CDCl3) δ 2.28 (s, 3H), 3.90
(s, 2H), 4.05 (brs, 1H), 6.29 (s, 1H), 6.56 (d, J ) 7.8 Hz, 1H),
6.69 (t, J ) 7.5 Hz, 1H), 6.88 (t, J ) 7.5 Hz, 1H), 7.03 (d, J )
7.8 Hz, 1H), 7.10 (d, J ) 7.8 Hz, 2H), 7.33 (d, J ) 7.8 Hz, 2H);
13C NMR (75 MHz, CDCl3) δ 21.7, 50.4 (3J CH ) 7.5 Hz), 116.8,
119.2, 120.5, 122.5, 126, 126.7, 129.1, 129.4, 130.6, 133.8, 137,
144.2; 13C NMR (75 MHz, CDCl3, DEPT 135) δ 21.4, 50.1
(inverted), 116.5, 120.2, 122.2, 125.7, 126.4, 128.8, 129.1. Anal.
Calcd for C16H15NS: C, 75.85; H, 5.97; N, 5.52. Found: C, 75.75;
H, 5.99; N, 5.76.
(E)-2-[(4-Met h oxyp h en yl)m et h ylid en e]-3,4-d ih yd r o-
2H-1,4-ben zoth ia zin e (61g): white solid; mp 186 °C; IR
3376.3, 1603, 1586.7, 1508.6 cm-1; 1H NMR (300 MHz, CDCl3)
δ 3.80 (s, 3H), 3.94 (s, 2H), 6.32 (s, 1H), 6.61 (d, J ) 7.8 Hz,
1H), 6.74 (t, J ) 7.5 Hz, 1H), 6.88-6.96 (m, 3H), 7.08 (d, J )
7.8 Hz, 1H), 7.44 (d, J ) 8.4 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 50.3, 55.6, 114.2, 114.5, 116.8, 119.1, 120.5, 122.2,
126, 126.7, 129.3, 130.5, 131.2, 144.2; 13C NMR (75 MHz,
CDCl3, DEPT 135) δ 50 (inverted), 55.3, 113.9, 116.5, 120.1,
121.9, 125.7, 126.4,130.2. Anal. Calcd for C16H15NOS: C, 71.34;
H, 5.61; N, 5.19. Found: C, 71.1; H, 5.60; N, 4.94.
122.1, 125.8, 126.4, 127, 128.5, 128.9. Anal. Calcd for C15H13
-
NS: C, 75.27; H, 5.47; N, 5.85. Found: C, 75.07; H, 5.36; N,
5.61.
Compounds 61b-m were synthesized by following the
procedure for 61a .
(E)-2-[(2-Th ien yl)m eth yliden e]-3,4-d ih yd r o-2H-1,4-ben -
zoth ia zin e (61h ): white solid; mp 219 °C; IR 3380.08, 1604.8,
(E)-2-[(1-Na p h t h yl)m et h ylid en e]-3,4-d ih yd r o-2H -1,4-
ben zoth ia zin e (61b): white solid; mp 185 °C; IR 3349.4,
1603.9, 1586.9, 1484.8 cm-1; 1H NMR (300 MHz, CDCl3) δ 4.03
(s, 2H), 6.56 (dd, J ) 8.1, 1.2 Hz, 1H), 6.64 (td, J ) 7.6, 1.2
Hz, 1H), 6.81 (s, 1H), 6.84 (dd, J ) 7.8, 1.5 Hz, 1H), 6.91 (td,
J ) 7.8, 1.5 Hz, 1H), 7.34-7.44 (m, 3H), 7.61 (d, J ) 7.5 Hz,
1H), 7.71 (d, J ) 8.1 Hz, 1H), 7.75-7.79 (m, 1H), 7.91-7.95
(m, 1H); 13C NMR (75 MHz, CDCl3) δ 49.9 (3J CH ) 7.5 Hz),
116.8, 119.3, 119.8, 120.5, 124.9, 125.7, 126, 126.3, 126.4,
1
1583.7 cm-1; H NMR (300 MHz, CDCl3) δ 3.99 (s, 2H), 4.18
(brs, 1H), 6.61 (s, 1H), 6.66 (d, J ) 8.1 Hz, 1H), 6.80 (td, J )
8.1, 1.2 Hz, 1H), 6.99 (td, J ) 8.1, 1.2 Hz, 1H), 7.03-7.06 (m,
1H), 7.15-7.2 (m, 2H), 7.33 (d, J ) 4.8 Hz, 1H); 13C NMR (75
MHz, CDCl3) δ 49.3, 115.3, 116.4, 118.3, 120.1, 125.6, 125.8,
126.5, 126.8, 127.2, 128.9, 139.4, 143.3; 13C NMR (75 MHz,
CDCl3) δ 49.5 (inverted), 115.5, 116.6, 120.3, 125.8, 126, 126.7,
127.1, 127.4. Anal. Calcd for C13H11NS2: C, 63.63; H, 4.52; N,
5.7. Found: C, 63.64; H, 4.41; N, 5.52.
126.7, 127.1, 128.4, 129, 131.9, 133.3, 134.1, 134.6, 144.1; 13
C
NMR (75 MHz, CDCl3, DEPT 135) δ 49.6 (inverted), 116.5,
119.6, 120.2, 124.6, 125.4, 125.7, 126, 126.2, 126.4, 126.8,
128.1, 128.7. Anal. Calcd for C19H15NS: C, 78.9; H, 5.22; N,
4.84. Found: C, 78.83; H, 5.24; N, 4.80.
(E)-2-[(5-Iod oth ien yl)m eth ylid en e]-3,4-d ih yd r o-2H-1,4-
ben zoth ia zin e (61i): white solid; mp 132 °C; IR 3365.5,
1600.4, 1595.8 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.95 (s, 2H),
4.19 (brs, 1H), 6.54 (s, 1H), 6.65 (dd, J ) 8.1, 1.2 Hz, 1H), 6.76-
6.82 (m, 2H), 6.99 (td, J ) 7.8, 1.2 Hz, 1H), 7.15-7.18 (m, 2H);
13C NMR (75 MHz, CDCl3) δ 49.6, 115.3, 117, 118.3, 120.6,
126.5, 126.9, 127.4, 128.9, 130.4, 137, 143.7, 146; 13C NMR (75
MHz, CDCl3, DEPT 135) δ 49.3 (inverted), 115, 116.7, 120.3,
126.2, 126.7, 128.6, 136.8. Anal. Calcd for C13H10INS2: C, 42.05;
H, 2.71; N, 3.77. Found: C, 42.09; H, 2.62; N, 3.67.
(E)-2-[(2-Na p h t h yl)m et h ylid en e]-3,4-d ih yd r o-2H -1,4-
1
ben zoth ia zin e (61c): white solid; mp 204 °C; H NMR (300
MHz, CDCl3 + DMSO-d6) δ 4.01 (s, 2H), 5.39 (s, 1H), 6.54 (s,
1H), 6.75 (d, J ) 9 Hz, 2H), 6.96 (t, J ) 6 Hz, 1H), 7.10 (d, J
) 6 Hz, 1H), 7.47 (d, J ) 3 Hz, 2H), 7.62 (t, J ) 9 Hz, 1H),
7.84 (t, J ) 9 Hz, 3H), 7.99 (s, 1H). 13C NMR (75 MHz, CDCl3
+ DMSO-d6) δ 53.4, 120.1, 121.4, 123.1, 125.1, 129.7, 130,
130.8, 131.1, 131.3, 131.5, 131.7, 135.7, 136.3, 137, 137.6,
(E)-2-[(4-Iod op h en yl)m eth ylid en e]-3,4-d ih yd r o-2H-1,4-
ben zoth ia zin e (61j): white solid; mp 202 °C; IR 3369.3,

Pd-Cu-Catalyzed Synthesis of Benzofused Heterocycles
J . Org. Chem., Vol. 66, No. 13, 2001 4575
1608.5, 1583, 1481.6 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.97
(s, 2H), 6.29 (s, 1H), 6.66 (dd, J ) 8.1, 0.9 Hz, 1H), 6.79 (td, J
) 7.5, 1.2 Hz, 1H), 6.99 (td, J ) 7.8, 1.2 Hz, 1H), 7.11 (dd, J
) 7.8, 1.5 Hz, 1H), 7.26 (d, J ) 8.4 Hz, 2H), 7.69 (d, J ) 8.4
Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 48.9, 115.4, 119.12,
mmol), bis(triphenylphosphine)palladium(II) dichloride (4 mg,
0.006 mmol, 3 mol %) and triethylamine (65 mg, 0.64 mmol)
in acetonitrile (5 mL) was heated at 80 °C (bath temperature)
for 15 h in an argon atmosphere. After removal of the solvent
and usual workup, a brown gum was obtained which after
purification through column chromatography on silica gel (60-
120 mesh) with the eluent being light petroleum/ethyl acetate
(19:1; V/V) afforded 62 as a light yellow solid; mp 150 °C; IR
119.8, 120, 122.8, 124.9, 126.1, 129.5, 131.7, 136.4, 142.8; 13
C
NMR (75 MHz, CDCl3, DEPT 135) δ 50.1 (inverted), 116.6,
120.5, 120.9, 126, 126.5, 130.7, 137.5. Anal. Calcd for C15H12
-
INS: C, 49.32; H, 3.31; N, 3.83. Found: C, 49.54; H, 3.21; N,
3.96.
3361.7, 1710.7, 1618.2, 1598.9 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 3.72 (s, 3H), 3.93 (s, 2H), 6.18 (d, J ) 15.6 Hz, 1H),
6.50 (s, 1H), 6.62 (d, J ) 8.1 Hz, 1H), 6.76 (t, J ) 7.8 Hz, 1H),
6.89-6.98 (m, 2H), 7.10-7.15 (m, 2H), 7.70 (d, J ) 15.6 Hz,
1H). Anal. Calcd for C17H15NO2S2: C, 61.98; H, 4.59; N, 4.25.
Found: C, 61.92; H, 4.63; N, 4.26.
(E)-2-[(2-Iod op h en yl)m eth ylid en e]-3,4-d ih yd r o-2H-1,4-
ben zoth ia zin e (61k ): white solid; mp 104 °C; IR 3377.1,
1606.6, 1585.4, 1508.2 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.95
(s, 2H), 6.30 (s, 1H), 6.58 (d, J ) 6 Hz, 1H), 6.69 (t, J ) 6 Hz,
1H), 6.82-6.98 (m, 3H), 7.30 (td, J ) 7.5, 0.9 Hz, 1H), 7.37
(dd, J ) 7.8, 1.2 Hz, 1H), 7.58 (d, J ) 6 Hz, 1H); 13C NMR (75
MHz, CDCl3) δ 49.7, 114.2, 116.8, 120.4, 122.2, 125.9, 126,
126.2, 126.7, 128.4, 129.2, 130, 130.5, 139.6, 144.1. 13C NMR
(75 MHz, CDCl3, DEPT 135) δ 49.4 (inverted), 113.9, 116.6,
120.3, 125.6, 125.9, 126.4, 128.1, 129.7, 130.3. Anal. Calcd for
C15H12INS: C, 49.32; H, 3.31; N, 3.83. Found: C, 49.50; N, 3.37;
N, 3.78.
(E)-2-[4-(2-P h en yleth yn yl)p h en yl]m eth ylid en e-3,4-d i-
h yd r o-2H-1,4-ben zoth ia zin e (63). Compound 61j (70 mg,
0.19 mmol) in acetonitrile (5 mL) was stirred with (PPh3)2-
PdCl2 (4 mg, 0.006 mmol, 3 mol %), CuI (2 mg, 0.01 mmol, 6
mol %) and triethylamine (77 mg, 0.76 mmol) at room
temperature for 1/2 h in an argon atmosphere. Phenylacety-
lene (40 mg, 0.39 mmol) was added, and the reaction mixture
was allowed to stir at room temperature for 24 h. After usual
workup, crude product was purified by column chromatogra-
phy on silica gel (60-120 mesh) with the eluent being light
petroleum/ethylacetate (19/1, V/V) to afford 63 as a light yellow
solid; mp 210 °C; IR 3361.7, 1585.8, 1487.1 cm-1; 1H NMR (300
MHz, CDCl3) δ 4.01(s, 2H), 6.38 (s, 1H), 6.67 (d, J ) 7.8 Hz,
1H), 6.79 (t, J ) 7.5 Hz, 1H), 6.99 (t, J ) 7.5 Hz, 1H), 7.15 (d,
J ) 7.8 Hz, 1H), 7.34-7.37 (m, 3H), 7.52-7.57 (m, 6H). Anal.
Calcd for C23H17NS: C, 81.38; H, 5.04; N, 4.12. Found: C, 81.19;
H, 4.98; N, 4.16.
(E)-4-Met h yl-2-(p -t olylm et h ylid en e)-3,4-d ih yd r o-2H -
1,4-ben zoth ia zin e (61l): white solid; mp 92 °C; IR 1604.6,
1
1585.6, 1511.61, 1488.51 cm-1; H NMR (300 MHz, CDCl3) δ
2.26 (s, 3H), 2.88 (s, 3H), 3.70 (s, 2H), 6.25 (s, 1H), 6.72 (t, J
) 7. Hz, 2H), 7.01 (td, J ) 7.8, 1.2 Hz, 1H), 7.09 (d, J ) 8.4
Hz, 3H), 7.33 (d, J ) 8.1 Hz, 2H); 13C NMR (75 MHz, CDCl3)
δ 21.2, 39.8, 58.8, 113.9, 119.7, 120.8, 121.2, 126, 126.1, 128.6,
128.9, 131, 133.4, 136.5, 146.9; 13C NMR (75 MHz, CDCl3,
DEPT 135) δ 21.4, 40, 59 (inverted), 114.1, 120, 121.4, 126.2,
126.4, 128.8, 129.2. Anal. Calcd for C17H17NS: C, 76.36; H, 6.41;
N, 5.23. Found: C, 76.45; H, 6.19; N, 5.16.
Ack n ow led gm en t. Thanks are due to Dr. S. A.
Imam of Huntington Medical Research Institute, Pasa-
dena, CA, for a gift of (PPh3)2PdCl2 which was very
helpful for the investigations reported in this paper.
Grateful acknowledgment is also made of a Royal
Society of Chemistry J ournals Grants for International
Authors to N.G.K. which made his visit to various
research institutes and universities in the U.K and
Europe possible.
(E)-4-Ben zyl-2-(p -t olylm et h ylid en e)-3,4-d ih yd r o-2H -
1,4-ben zoth ia zin e (61m ): white solid; mp 110 °C; IR 1604.1,
1579.9, 1484.6 cm-1; 1H NMR (300 MHz, CDCl3) δ 2.34 (s, 3H),
3.78 (s, 2H), 4.43 (s, 2H), 6.16 (s, 1H), 6.82 (q, J ) 8.1 Hz,
2H), 7.01 (t, J ) 7.5 Hz, 1H), 7.18 (t, J ) 7.2 Hz, 3H), 7.25-
7.41 (m, 7H); 13C NMR (75 MHz, CDCl3) δ 21.2, 55.4, 56.1,
116.5, 120.1, 121.4, 121.7, 125.8, 126.3, 127.2, 127.7, 128.6,
129, 129.9, 133.4, 136.5, 137.9, 146.2; 13C NMR (75 MHz,
CDCl3, DEPT 135) δ 21.4, 55.6 (inverted), 56.3 (inverted),
116.7, 120.3, 121.9, 126, 126.5, 127.5, 127.9, 128.8, 129.2. Anal.
Calcd for C23H21NS: C, 80.42; H, 6.16; N, 4.07. Found: C, 80.39;
H, 6.18; N, 4.16.
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
and 13C NMR spectra of compounds 28, 29, 33, 42, 45, 52, 61b,
61e, 61h , 61l. This material is available free of charge via the
Internet at http://pubs.acs.org
(E)-2-[5-(2-Ca r b om et h oxyvin yl)t h ien yl]m et h ylid en e-
3,4-d ih yd r o-2H-1,4-ben zoth ia zin e (62). A mixture of com-
pound 61i (60 mg, 0.16 mmol), methyl acrylate (40 mg, 0.46
J O001783+