A ligand free copper(II) catalyst is as effective as a ligand assisted Pd(II) catalyst towards intramolecular C-S bond formation via C-H functionalization

Article abstract of DOI:10.1016/j.tet.2013.08.025

Copper(I) catalysts are usually ineffective on the other hand Pd(II) catalysts are quite effective in promoting intramolecular sp² C-H functionalization (C-S bond formation). Herein, we have developed a ligand assisted Pd(II) catalyzed C-S bond formation via C-H activation from arylthioureas leading to the formation of 2-aminobenzothiazoles for substrates bearing electron donating (EDG) groups in the aryl ring. However without the assistance of ligand this Pd(II) catalyzed reaction is quite unproductive particularly for thioureas possessing strongly electron donating groups in the aryl rings. Interestingly, the ligand free Cu(II) catalyzed oxidative cyclization of arylthioureas are equally effective both for arylthioureas possessing electron donating as well as electron withdrawing groups in the aryl rings.

Full text of DOI:10.1016/j.tet.2013.08.025

Tetrahedron 69 (2013) 9096e9104
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A ligand free copper(II) catalyst is as effective as a ligand assisted
Pd(II) catalyst towards intramolecular CeS bond formation via CeH
functionalizationq
*
Arghya Banerjee, Sourav Kumar Santra, Saroj Kumar Rout, Bhisma K. Patel
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 June 2013
Received in revised form 30 July 2013
Accepted 13 August 2013
Available online 20 August 2013
Copper(I) catalysts are usually ineffective on the other hand Pd(II) catalysts are quite effective in pro-
moting intramolecular sp2 CeH functionalization (CeS bond formation). Herein, we have developed
a ligand assisted Pd(II) catalyzed CeS bond formation via CeH activation from arylthioureas leading to
the formation of 2-aminobenzothiazoles for substrates bearing electron donating (EDG) groups in the
aryl ring. However without the assistance of ligand this Pd(II) catalyzed reaction is quite unproductive
particularly for thioureas possessing strongly electron donating groups in the aryl rings. Interestingly, the
ligand free Cu(II) catalyzed oxidative cyclization of arylthioureas are equally effective both for arylth-
ioureas possessing electron donating as well as electron withdrawing groups in the aryl rings.
Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
Keywords:
CeH functionalization
CeS bond formation
Cu-catalysis
Pd-catalysis
Ligand assistance
1. Introduction
inert toward dehalogenative CeS bond formation gave anti-
Hugerschoff products via an oxidative dimerization path with re-
2-Aminobenzothiazoles (Hugerschoff product), are obtained
from unsymmetrical aryl-sec-alkyl thioureas (Tu) using molecular
bromine (or its equivalent) or iodine.1 Although activated aromatics
(substrates possessing electron donating groups) undergo intra-
molecular aromatic electrophilic substitution to give the
Hugerschoff product 2-aminobenzothiazoles2 but most other sub-
strates gave thioamidoguanidines (Tag) (anti-Hugerschoff pro-
duct)2a exclusively via an oxidative dimerization path (path A,
Scheme 1). In order to suppress the competitive formation of
Hugerschoffs and to give anti-Hugerschoff products exclusively
a strategy has been developed by our group, wherein the Cu(II) salt
promotes an oxidative dimerization (SeS bond formation) of
thiourea, which is the essential intermediate for the formation of
anti-Hugerschoff product (path A, Scheme 1).3 During the forma-
tion of anti-Hugerschoff product from aryl-sec-alkyl thiourea (Tu)
no CeH activation (CeS bond formation) was observed at room
temperature. 2-Halo (eF, eCl) arylthioureas, which are usually
dox active Cu(II) salt at room temperature (Path B, Scheme 1).3
However, at an elevated temperature CeS bond formation leading
to the synthesis of 2-aminobenzothiazole was observed using Cu(II)
(path C, Scheme 1).3 The same dehalogenative CeS bond formation
was achieved using CuI4 and CuO nanoparticle5 in water at an el-
evated temperature (path C, Scheme 1). Further, it has been ob-
served that Cu(I) prefers a dehalogenative path over CeH activation
for the entire range of halogens (eF, eCl, eBr, eI) (path C, Scheme
1) and in the absence of any 2-halo groups it is unproductive
whereas a Pd-catalyzed reaction favors a dehalogenative path for
activated halogens (eBr, eI) (path D, Scheme 1) and CeH activation
path (CeS bond formation) for less activated halogens (eF, eCl)
(path E, Scheme 1).6
Of late transition metal catalyzed CeH functionalization is an
exciting area of research, representing an atom-economic and
greener prospective, which improves the overall efficacy of syn-
thetic processes. The ubiquitous CeH bonds can now be considered
as dormant synthetic equivalents of several reactive functional
groups. Among the various transition metal catalysts employed for
this process, Pd and Cu are the most well explored ones.7 Usually Cu
catalyzed reactions are preferred due to the cost consideration and
better environmental acceptability whereas Pd-catalyzed reactions
are superior in spite of high cost due to its efficacy and high turn-
over numbers.8
q
This is an open-access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike License, which permits non-
commercial use, distribution, and reproduction in any medium, provided the
original author and source are credited.
* Corresponding author. E-mail address: patel@iitg.ernet.in (B.K. Patel).
0040-4020/$ e see front matter Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.025

A. Banerjee et al. / Tetrahedron 69 (2013) 9096e9104
9097
N
Scheme 1. Fate of Cu and Pd catalyzed reactions of thioureas.
No doubt our Pd(II) catalyzed synthesis of 2-aminobenz-
othiazole via CeH activation strategy is quite promising (path E,
Scheme 1) but the methodology is applicable mostly for substrates
possessing electron withdrawing groups (EWG) in the aromatic
rings.6 For substrates possessing strongly electron donating groups,
such as eOMe, eOBu the reaction failed to give any product. Batey
et al. have made similar observations, i.e., lower yield in case of
thioureas possessing electron donating groups and for more acti-
vated substrates possessing multiple electron donating groups as in
the case of (m,m-Me, m,m,p-OMe) the desired product was not
obtained at all.9 Two more alternative synthesis of similar scaffold
has been achieved via the CeH activation (CeS bond formation) of
o-aryl sp2 CeH bond of N-arylthioamides using Pd(II) catalyst.10
Very recently a iron(II) catalyzed synthesis of 2-substituted ben-
zothiazole from N-arylbenzothioamide via an oxidative CeH
functionalization (CeS bond formation) is reported by Lei et al.11
Buchwald et al. also demonstrated a Cu(OAc)2-catalyzed synthesis
of benzimidazoles from corresponding amines through a CeH ac-
tivation (CeN bond formation) process.12 Nagasawa group13 has
reported a copper catalyzed intramolecular CeO bond formation
via CeH activation strategy using N-arylurea as the precursor in an
oxygen atmosphere. Recently, a copper catalyzed intramolecular
CeO bond formation strategy has been demonstrated by our group
for the synthesis of 1,3,4-oxadiazoles via an imine CeH bond
functionalization.14 Thus, a query arises whether an intramolecular
CeS bond formation via CeH functionalization could be achieved
from thioureas using environmentally acceptable low cost catalyst,
such as copper.
2-aminobenzothiazole from N-arylthiourea following the CeH
functionalization strategy.
2. Results and discussion
Among various Cu(II) salts Cu(OTf)2 is the most efficient in
promoting intramolecular CeO bond formation via sp2 CeH bond
activation as has been demonstrated by our group as well as by
Nagasawa et al.13,14 Taking cues from these we used Cu(OTf)2 to-
ward the intramolecular CeS bond formation of N-arylthiourea (1a)
via a CeH bond functionalization strategy. Accordingly, N-arylth-
iourea (1a) was reacted with Cu(OTf)2 (10 mol %), in DMF the de-
sired product 2-aminobenzothiazole (1a0) was obtained in
a moderate yield of 40% (Table 1, entry 1). Further, optimizations
were carried out to arrive at the best possible yield as shown in
Table 1. During the optimization it was observed that the reaction
did not proceed in solvents like acetone, 1,4-dioxane, acetonitrile
Table 1
Screening of reaction conditions
Entry
Catalyst (mol %)
Solvent
Yield (%)
1
2
3
4
5
6
7
8
Cu(OTf)2 (10.0)
Cu(OTf)2 (10.0)
Cu(OTf)2 (10.0)
Cu(OTf)2 (10.0)
Cu(OTf)2 (10.0)
Cu(OTf)2 (10.0)
Cu(OTf)2 (20.0)
CuCl2 (10.0)
DMF
40
Acetone
1,4-Dioxane
CH3CN
No reaction
No reaction
No reaction
25
65
68
There is no prior report on the synthesis of 2-aminobenzothiazole
via a CeH functionalization using cheap and environmentally ac-
ceptable catalyst like copper. On the other hand synthesis of
2-aminobenzothiazoles using Pd-catalyzed intramolecular CeS bond
formation via CeH functionalization should also be improved and
a method should also be developed, which should work for sub-
strates possessing both electron donating as well as electron with-
drawing groups. Herein a systematic study has been carried out on
the differential selectivity for Cu and Pd catalyzed synthesis of
DMSO
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
No reaction
No reaction
20
9
10
11
CuBr2 (10.0)
Cu(OAc)2 (20.0)
Cu(OTf)2 (10.0)
85a
Bold value signifies the most optimized condition.
a
Reaction performed under O2 atmosphere.

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A. Banerjee et al. / Tetrahedron 69 (2013) 9096e9104
(Table 1, entries 2, 3, and 4). The use of polar aprotic solvent, such as
DMSO gave a poor yield of the product (25%) (Table 1, entry 5).
Switching the solvent to toluene the desired product (1a0) was
obtained in an improved yield of 65% (Table 1, entry 6). No signif-
icant improvement was observed in the product yield when the
catalyst loading was increased to 20 mol % (68%) (Table 1, entry 7).
The reactions did not provide the desired product 2-
aminobenzothiazole (1a0) when other Cu(II) salts, such as CuCl2
and CuBr2 were used (Table 1, entries 8 and 9). It is pertinent to
mention that the analogous substrate with CuBr2 gave thio-
aminoguanidines3 however under this reaction conditions the
same product is not formed, which is probably due to the difference
in the reaction conditions and the quantity of CuBr2 used. Although
the desired transformation could be achieved using Cu(OAc)2 but
the yield was poor (20%) (Table 1, entry 10). By carrying out the
reaction at 110 ꢀC under an oxygen atmosphere in toluene using
Cu(OTf)2 (10 mol %) as the catalyst the yield improved upto 85%
(Table 1, entry 11). No further improvement in the yield was ob-
served when the temperature was increased above 110 ꢀC but the
yield decreased with decrease in the reaction temperature.
Thioureas generated in situ by reacting phenyl isothiocyanate
(1) and secondary amines, such as morpholine (a), piperidine (b),
pyrrolidine (c), N-substituted piperazine (d), 4-benzylpiperidin (e),
and thiomorpholine (f) all provided moderate to good yields of
their desired products (1a0e1f0) via this novel CeH activation (CeS
bond formation) protocol as shown in Table 2. On the other hand
thioureas generated in situ by reacting phenyl isothiocyanate (1)
and primary amines like, benzyl amine, aniline etc. did not provide
desired products under this reaction conditions. This is possibly
because of the competitive co-ordination of the second nitrogen to
metal thereby preventing o-metalation, which is essential for this
transformation.
Further, the scope of this protocol was examined using varieties
of N-arylthioureas derived from different aryl isothiocyanates and
morpholine as the secondary amine (Table 3). Thioureas possessing
electron withdrawing and electron donating substituents in the
aromatic core all provided their desired products in good to ex-
cellent yields (Table 3). For N-arylthiourea possessing electron
withdrawing substituents in the aromatic ring, such as m-Cl (2a),
Table 3
Cu catalyzed synthesis of 2-aminobenzothiazoles
Entry
1
Substrate
Product
Time (h)/
Yield (%)a
12/85
11/78
12/76
10/75
9/80
2
3
4
5
6
7
8
9
Table 2
Cu catalyzed synthesis of 2-aminobenzothiazoles.from aryl-sec-alkyl thioureas
Entry
1
Substrate
Product
Yield (%)a
85
2
3
80
68
9.5/85
10/84
8/81
4
5
75
7.5/83
6/82
70
75
10
6
a
a
Yields of pure isolated products after silica gel column chromatography.
Yields of pure isolated products after silica gel column chromatography.

A. Banerjee et al. / Tetrahedron 69 (2013) 9096e9104
9099
p-F (3a), p-Br (4a) all provided their corresponding products (2a0),
(3a0) and (4a0), respectively. In the case of o-halo (eCl, eF)
substituted arylthioureas (5a) and (6a) both gave benzothiazole
(1a0) via a dehalogenative path and not by CeH functionalization.
Formation of benzothiazole (1a0) for substrates (5a) and (6a) sup-
ports our previous observation where a Cu catalyzed reaction
prefers dehalogenative CeS bond formation over the CeH activa-
tion path. The preferential dehalogenative CeS bond formation
over CeH activation was further confirmed with substrate (7a)
bearing o-F group, which gave corresponding benzothiazole (3a0)
again via a dehalogenative path. Similarly, N-arylthioureas pos-
sessing electron donating substituents, such as p-Me (8a), p-Bu (9a)
and 2,4 di-Me (10a), on the aryl ring all underwent intramolecular
CeS bond formation via CeH functionalization giving their corre-
sponding benzothiazoles (8a0), (9a0) and (10a0), respectively.
During this copper catalyzed intramolecular CeS bond forma-
tion protocol it was observed that the presence of electron donating
substituents, such as eMe (8a), eBu (9a) and 2,4-di-Me (10a) in the
aromatic scaffolds provided their corresponding benzothiazoles in
a shorter reaction time than the substrates bearing electron with-
drawing substituents eCl (2a), eF (3a) and eBr (4a). This obser-
vation is consistent with the findings of Nagasawa et al. and
others.13 These results indirectly support the oxidative cyclization
mechanism where copper triflate is initially coordinated to the
sulfur atom leading to a directed ortho-metalation by an electro-
philic aromatic substitution path. In the next step formation of a six
membered metallacycle is followed by a concomitant reductive
elimination to give 2-aminobenzothiazole. The Cu(0) species gen-
erated in this step is oxidized to Cu(II) with molecular oxygen
thereby maintaining the catalytic cycle (Scheme 2).
functionalizations.15 Therefore we thought to employ a ligand
assisted Pd-catalyzed protocol for arylthioureas possessing electron
donating groups in the aromatic rings. Bidentate 1,10-
phenanthroline is a well explored ligand in several Pd-catalyzed
CeH functionalization reactions,16 which was chosen for this pur-
pose. Interestingly the substrate N-(4-methoxyphenyl)morpholine-
4-carbothioamide (12a) when reacted in the presence of 5 mol % of
Pd(OAc)2 along with 15 mol % of 1,10-phenanthroline and 1 equiv of
K2CO3 provided the desired product (12a0) in 91% isolated yield.
With this initial success other ligands, such as L-proline, ethyl-
enediamine, 2,20-bipyridyl and ethane 1,2-diol were employed for
this purpose but all of them gave inferior yields 60%, 5%, 50%, and
35%, respectively, as compared to 1,10-phenanthroline. Other sol-
vents, such as DMSO,1,4-dioxane, toluene, acetonitrile, and acetone
and bases, such as NaHCO3, NaOH, KOH tested were found to be not
so effective. Further decreasing the catalyst loading to 2 mol % and
ligand loading to 5 mol % the yield remained unchanged (90%).
Therefore 2 mol % of Pd(OAc)2 along with 1,10-phenanthroline
(5 mol %) in DMF solvent and using K2CO3 as the base was found
to be the most optimized conditions used for all other substrates
bearing electron donating substituents in the aromatic core of
arylthioureas.
With the above optimized reaction conditions in hand thio-
ureas (8a) and (8b) possessing electron donating substituent (p-
Me) gave corresponding 2-aminobenzothiazoles (8a0) and (8b0) in
excellent yields (Table 4). Similarly p-butyl substituted thioureas
(9a) and (9b) were reacted and corresponding 2-aminoben-
zothiazoles (9a0) and (9b0) were isolated in good yields. Sterically
hindered 2,4 di-Me substituted thioureas (10a) and (10b) un-
derwent intramolecular CeS bond formation via CeH activation
giving 2-aminobenzothiazoles (10a0) and (10b0), respectively, in
excellent yields. 2-Aminobenzothiazoles (11a0) and (11b0) were
obtained regioselectively from their 3,4 di-Me substituted thio-
ureas (11a) and (11b) as evident from their 1H NMR. It may be
reiterated that the synthesis of 2-aminobenzothiazoles from
thioureas were not so successful using Pd(II) catalyzed reaction
particularly for substrates possessing strongly electron donating
groups.6,9 However the present ligand assisted Pd(II) catalyzed
synthesis was quite successful even for substrate possessing
strongly electron donating groups as has been demonstrated for
substrates (12a), (12b), (13a), and (13b) giving their desired
products (12a0), (12b0), (13a0), and (13b0) (Table 4) respectively, in
excellent yields confirming the active role of ligand in tuning the
catalytic activity of Pd(II). The method was however not so suc-
cessful for substrate possessing electron donating substituent in its
ortho position as was observed for substrate (14a). In the later case
the product (14a0) was obtained in a mere yield of 45% along with
the recovery of starting material (45%) and slight decomposition to
its corresponding amine (10%). The failure to obtain product (14a0)
in good yield could be partly due to the steric hindrance from the
ortho methoxy group or in achieving the desired transition state
for this transformation.
Formation of benzothiazoles from thioureas bearing electron
donating groups is possibly going via the mechanism as shown in
Scheme 3. Initially the in situ generated Pdephen complex (I),
derived from Pd(OAc)2 and 1,10-phenanthroline, is coordinated to
sulfur atom of N-arylthiourea giving complex (II). The complex
(II) is transformed into a six membered palladacycle giving in-
termediate complex (III). This is then followed by a base-
mediated deprotonative metalation with the expulsion of an ac-
etate group giving intermediate (IV) as proposed by Inamoto
et al.10b Subsequent reductive elimination provides 2-
aminobenzothiazole with concomitant generation of Pd(0) spe-
cies (V). The in situ generated Pd(0) is further oxidized to Pd(II)
by an aerial oxidation, which maintains the catalytic cycle as
shown in Scheme 3.
Scheme 2. Plausible mechanism for Cu catalyzed oxidative cyclization of N-
arylthiourea.
The most notable aspects of the Pd(II) catalyzed CeH activation
(CeS bond formation) leading to the synthesis of benzothiazole is,
it still prefers CeH activation even in the presence of o-halo (eCl,
eF) substituents in thioureas.6 The above mentioned Cu(OTf)2
catalyzed strategy prefers dehalogenative path even in the pres-
ence of less reactive halogens (eCl, eF) and not the CeH func-
tionalization path. However this Pd-catalyzed method of CeH
functionalization was not successful particularly for arylthioureas
possessing strongly electron donating groups, such as (eOMe,
eOBu). Under the present reaction conditions such thioureas (12a)
and (13a) decomposed to their corresponding amines rather than
giving the expected 2-aminobenzothiazoles. Therefore a further
tuning of the Pd-catalyst is indeed necessary, which should work
both for substrates possessing electron donating as well as electron
withdrawing groups.
Ligands are known to assist metals in tuning their reactivity
and have been used widely for various Pd-catalyzed CeH

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A. Banerjee et al. / Tetrahedron 69 (2013) 9096e9104
Table 4
Synthesis of 2-aminobenzothiazole from electron donating N-arylthioureas
Entry
1
Substrate
Product
Yield (%)a
91
2
3
4
5
6
7
8
9
92
91
88
92
91
85
87
90
10
11
89
90

A. Banerjee et al. / Tetrahedron 69 (2013) 9096e9104
9101
Table 4 (continued )
Entry
Substrate
Product
Yield (%)a
12
89
13
45b
a
Yields of pure isolated products after silica gel column chromatography.
45% starting material recovered.
b
Scheme 3. Plausible pathway for ligand assisted Pd-catalyzed synthesis of 2-aminobenzothiazole.
3. Conclusions
Columns were typically packed as slurry and equilibrated with the
appropriate solvent system prior to use. 1H NMR (400 MHz) and 13
C
In conclusion we have developed two independent strategies for
the synthesis of 2-aminobenzothiazoles from thioureas, the first
one is via an intramolecular CeH functionalization (CeS bond for-
mation) using environmentally benign Cu-catalyst, Cu(OTf)2. In the
second approach a ligand assisted Pd(OAc)2 catalyzed strategy is
applied for thioureas possessing electron donating substituents in
the aromatic rings. It may be mentioned here that the second
strategy is not effective in the absence of ligand. Thus the cheap
environmentally acceptable Cu(II) catalyst is as effective as that of
a ligand assisted expensive Pd(II) catalyst towards intramolecular
CeS bond formation via CeH functionalization.
NMR (100 MHz) spectra were recorded on FT-400 MHz instrument
using TMS as an internal standard. Data are presented as follows:
chemical shift (parts per million), multiplicity (s¼singlet,
d¼doublet, t¼triplet, quin¼quintet, m¼multiplet, b¼broad, br
s¼broad singlet, br m¼broad multiplet), coupling constant J
(Hertz). Elemental analyses were carried out on an automatic car-
bon, hydrogen, nitrogen, and sulfur analyser. Melting points were
recorded and are uncorrected. IR spectra were recorded in KBr or
neat.
4.2. General procedure for preparation of substituted 2-
morpholinobenzo[d]thiazoles from substituted N-(phenyl)
morpholine-4-carbothioamide using Cu(OTf)2 (1e10)
4. Experimental section
4.1. General remarks
Substituted phenyl isothiocyanate (1e10) (1.5 mmol) was
treated with morpholine a (1.5 mmol) under neat condition and
instant formation of the corresponding thiourea was observed. To
this in situ generated thiourea toluene (2 mL) was added and
medium was stirred at room temperature for 5 min followed by
the addition of copper triflate (10 mol %). After that the reaction
mixture was subjected to reflux in a preheated oil bath at 110 ꢀC
Unless otherwise stated, all reagents were purchased from
commercial sources and used without further purification. Reaction
progress was monitored by TLC using silica gel 60 F254 (0.25 mm)
with detection by UV or iodine. Chromatography was performed
using silica gel (60e120) mesh size with freshly distilled solvents.

9102
A. Banerjee et al. / Tetrahedron 69 (2013) 9096e9104
under O2 atmosphere. The progress of the reaction was monitored
by TLC. After the completion of the reaction as judged from TLC
the reaction mixture was cooled and then admixed with water
(1 mL) and the product was extracted with ethyl acetate
(2ꢁ10 mL). The organic layer was dried over anhydrous sodium
sulfate (Na2SO4), filtered and evaporated under reduced pressure.
The crude products so obtained were further purified through
silica gel column chromatograph (hexane/ethyl acetate, 9:1) to
yield the pure substituted 2-morpholinobenzo[d]thiazole
(1a0e10a0). The identity and purity of the product was further
confirmed by spectroscopic analysis. Reaction performed with
phenyl isothiocyanate (1) (1.5 mmol) and other secondary amines
(bef) (1.5 mmol) in the above mentioned method and corre-
sponding benzo[d]thiazoles (1b0ef0) were isolated and spectro-
scopically characterized.
48.4; HRMS (ESI) calcd for C17H17N3S (MþHþ) 296.1216, found
296.1214.
4.2.5. 2-(4-Benzylpiperidin-1-yl)benzo[d]thiazole (1e0). The general
procedure was followed. The product was purified by column
chromatography (10% EtOAc/hexane) to give the title compound 1e0
(215 mg, 70%) as white solid; Rf (10% EtOAc/hexane) 0.26; mp
114 ꢀC; nmax (KBr): 3061, 3024, 2937, 2920, 2851, 1595, 1539, 1492,
1444, 1388, 1324, 1278, 1258, 1172, 922, 752, 727 cmꢂ1
;
1H NMR
7.60 (t, 2H, J¼6.4 Hz, Ar. CeH), 7.32 (m, 2H, Ar.
(400 MHz, CDCl3):
d
CeH), 7.26 (d, 1H, J¼7.2 Hz, Ar. CeH), 7.18 (d, 2H, J¼8.0 Hz, Ar. CeH),
7.08 (t, 2H, J¼8.0 Hz, Ar. CeH), 4.15 (d, 2H, J¼13.2 Hz,
aliphaticeCH2e), 3.06 (t, 2H, J¼12.8 Hz, aliphaticeCH2e), 2.59 (d,
2H, J¼7.2 Hz, aliphaticeCH2e), 1.77 (d, 4H, J¼10.8 Hz,
aliphaticeCH2e), 1.37 (m, 1H, aliphatic CeH); 13C NMR (100 MHz,
CDCl3):
d 168.7, 153.0, 139.9, 130.8, 129.2, 128.4, 126.2, 126.0, 121.2,
4.2.1. 4-(Benzo[d]thiazol-2-yl)morpholine (1a0). The general pro-
cedure was followed. The product was purified by column chro-
matography (10% EtOAc/hexane) to give the title compound 1a0
(187 mg, 85%) as white solid; Rf (10% EtOAc/hexane) 0.24; mp
122 ꢀC; nmax (KBr): 2918, 2854, 1591, 1537, 1441, 1377, 1289, 1229,
120.7, 118.9, 49.0, 43.0, 38.0, 31.5; HRMS (ESI) calcd for C19H20N2S
(MþHþ) 309.0955, found 309.0959.
4.2.6. 2-Thiomorpholinobenzo[d]thiazole (1f0). The general pro-
cedure was followed. The product was purified by column chro-
matography (10% EtOAc/hexane) to give the title compound 1f0
(187 mg, 75%) as yellow gum; Rf (10% EtOAc/hexane) 0.22; nmax
(KBr): 3059, 2936, 2858, 1599, 1531, 1444, 1385, 1359, 1313, 1218,
1113, 1067, 1032, 945, 859, 756 cmꢂ1 1H NMR (400 MHz, CDCl3):
;
d
7.57 (dd, 2H, J1¼6.4 Hz, J2¼4.0 Hz, Ar. CeH), 7.27 (t, 1H, J¼8.0 Hz,
Ar. CeH), 7.07 (t, 1H, J¼7.6 Hz, Ar. CeH), 3.80 (t, 4H, J¼4.4 Hz,
aliphaticeCH2e), 3.59 (t, 4H, J¼4.4 Hz, aliphaticeCH2e); 13C NMR
1054, 1020, 899, 750 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d 7.57 (d, 1H,
(100 MHz, CDCl3):
d
169.0, 152.5, 130.6, 126.1, 121.7, 120.8, 119.4,
J¼7.6 Hz, Ar. CeH), 7.52 (d, 1H, J¼8.0 Hz, Ar. CeH), 7.28 (t, 1H,
J¼8.0 Hz, Ar. CeH), 7.06 (t, 1H, J¼7.2 Hz, Ar. CeH), 3.93 (t, 4H, J¼4.8,
aliphaticeCH2e), 2.71 (t, 4H, J¼5.2 Hz, aliphaticeCH2e); 13C NMR
66.2, 48.5; Anal. Calcd for C11H12N2OS: C, 59.97; H, 5.49; N, 12.72;
Found C, 60.02; H, 5.55; N, 12.69.
(100 MHz, CDCl3):
d 168.2, 152.7, 130.8, 126.2, 121.6, 120.8, 119.2,
4.2.2. 2-(Piperidin-1-yl)benzo[d]thiazole (1b0). The general pro-
cedure was followed. The product was purified by column chro-
matography (10% EtOAc/hexane) to give the title compound 1b0
(174 mg, 80%) as white solid; Rf (10% EtOAc/hexane) 0.25; mp
96.5 ꢀC; nmax (KBr): 3063, 2939, 2922, 2848, 1590, 1535, 1440, 1385,
51.3, 26.7; Anal. Calcd for C11H12N2S2: C, 55.90; H, 5.12; N, 11.85;
found C, 55.93; H, 5.18; N, 11.79.
4.2.7. 4-(5-Chlorobenzo[d]thiazol-2-yl)morpholine (2a0). The gen-
eral procedure was followed. The product was purified by column
chromatography (10% EtOAc/hexane) to give the title compound 2a0
(198 mg, 78%) as white solid; Rf (10% EtOAc/hexane) 0.23; mp
108 ꢀC; nmax (KBr): 3051, 2978, 2930, 2902, 2855, 1737, 1587, 1530,
1437, 1375, 1325, 1279, 1234, 1142, 1110, 1070, 1035, 885, 872, 808,
1333,1287,1258,1212,1121,1009, 935, 902, 811, 761, 730, 648 cmꢂ1
;
1H NMR (400 MHz, CDCl3):
d
7.54 (d, 2H, J¼7.6 Hz, Ar. CeH), 7.25 (t,
1H, J¼5.4 Hz, Ar. CeH), 7.02 (t, 1H, J¼7.2 Hz, Ar. CeH), 3.55 (s, 4H,
aliphaticeCH2e), 1.63 (s, 6H, aliphaticeCH2e); 13C NMR (100 MHz,
CDCl3):
d
168.9, 153.0, 130.7, 125.9, 121.1, 120.6, 118.8, 49.6, 25.3,
678, 632, 603 cmꢂ1 1H NMR (400 MHz, CDCl3):
; d 7.54 (s, 1H, Ar.
24.3; Anal. Calcd for C12H14N2S: C, 66.02; H, 6.46; N, 12.83; found C,
66.08; H, 6.50; N, 12.76.
CeH), 7.49 (d, 1H, J¼8.4 Hz, Ar. CeH), 7.06 (d, 1H, J¼2.6 Hz, Ar. CeH),
3.82 (t, 4H, J¼5.0 Hz, aliphaticeCH2e), 3.61 (t, 4H, J¼5.0 Hz,
aliphaticeCH2e); 13C NMR (100 MHz, CDCl3):
d 170.1, 153.8, 132.1,
4.2.3. 2-(Pyrrolidin-1-yl)benzo[d]thiazole (1c0). The general pro-
cedure was followed. The product was purified by column chro-
matography (10% EtOAc/hexane) to give the title compound 1c0
(138 mg, 68%) as white solid; Rf (10% EtOAc/hexane) 0.22; mp
101 ꢀC; nmax (KBr): 2950, 2868, 1604, 1561, 1544, 1442, 1365, 1341,
129.0, 121.7, 121.5, 119.4, 66.3, 48.5; HRMS (ESI) calcd for
C
11H11N2OClS (MþHþ) 255.0353, found 255.0350.
4.2.8. 4-(6-Fluorobenzo[d]thiazol-2-yl)morpholine (3a0). The gen-
eral procedure was followed. The product was purified by column
chromatography (10% EtOAc/hexane) to give the title compound 3a0
(180 mg, 76%) as white solid; Rf (10% EtOAc/hexane) 0.21; mp
145 ꢀC; nmax (KBr): 3058, 2982, 2906, 2883, 2864, 2845, 1903, 1674,
1611, 1539, 1459, 1376, 1343, 1287, 1235, 1181, 1112, 1073, 1029, 948,
1317, 1276, 1258, 1175, 1120, 1069, 859, 747, 720 cmꢂ1
(400 MHz, CDCl3):
;
1H NMR
d
7.58 (d, 2H, J¼8.4 Hz, Ar. CeH), 7.28 (t, 1H,
J¼7.6 Hz, Ar. CeH), 7.03 (t, 1H, J¼7.6 Hz, Ar. CeH), 3.56 (m, 4H,
aliphaticeCH2e), 2.06 (m, 4H, aliphaticeCH2e); 13C NMR
(100 MHz, CDCl3):
d
165.5, 153.4, 130.8, 126.0, 120.8, 120.7, 118.7,
920, 844, 805, 710, 651 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d 7.50 (m,
49.6, 25.7; Anal. Calcd for C11H12N2S: C, 64.67; H, 5.92; N, 13.71;
found C, 64.71; H, 5.95; N, 13.68.
1H, Ar. CeH), 7.31 (d, 1H, J¼8 Hz, Ar. CeH), 7.03 (t, 1H, J¼9 Hz, Ar.
CeH), 3.80e3.82 (m, 4H, aliphaticeCH2e), 3.57 (t, 4H, J¼4.8 Hz,
aliphaticeCH2e); 13C NMR (100 MHz, CDCl3):
d 168.7, 159.5, 157.1,
4.2.4. 2-(4-Phenylpiperazin-1-yl)benzo[d]thiazole (1d0). The gen-
eral procedure was followed. The product was purified by column
chromatography (10% EtOAc/hexane) to give the title compound
1d0 (221 mg, 75%) as white solid; Rf (10% EtOAc/hexane) 0.24; mp
170 ꢀC; nmax (KBr): 3026, 2861, 1594, 1560, 1539, 1503, 1443, 1384,
149.0, 131.3, 119.9, 119.8, 114.0, 113.8, 107.7, 107.5, 66.6, 48.5; HRMS
(ESI) calcd for C11H11N2OFS (MþHþ) 239.0649, found 239.0651.
4.2.9. 4-(6-Bromobenzo[d]thiazol-2-yl)morpholine (4a0). The gen-
eral procedure was followed. The product was purified by column
chromatography (10% EtOAc/hexane) to give the title compound 4a0
(222 mg, 75%) as white solid; Rf (10% EtOAc/hexane) 0.25; mp
165e167 ꢀC; nmax (KBr): 2918, 2857, 1591, 1535, 1443, 1372, 1280,
1347, 1293, 1249, 1229, 1194, 1158, 1024, 935, 755 cmꢂ1
(400 MHz, CDCl3):
;
1H NMR
d
7.62 (d, 2H, J¼8.0 Hz, Ar. CeH), 7.33 (m, 3H,
Ar. CeH), 7.10 (t, 1H, J¼8.0 Hz, Ar. CeH), 6.94 (m, 3H, Ar. CeH),
3.78 (t, 4H, J¼5.2 Hz, aliphaticeCH2e), 3.29 (t, 4H, J¼5.2 Hz,
1258, 1229, 1110, 1026, 940, 863, 813 cmꢂ1
CDCl3):
J¼4.8 Hz, aliphaticeCH2e), 3.57 (t, 4H, J¼4.8 Hz, aliphaticeCH2e);
;
1H NMR (400 MHz,
aliphaticeCH2e); 13C NMR (100 MHz, CDCl3):
d
168.7, 152.8,
d 7.68 (s, 1H, Ar. CeH), 7.37 (s, 2H, Ar. CeH), 3.80 (t, 4H,
151.0, 130.9, 129.3, 126.2, 121.7, 120.8, 120.7, 119.3, 116.9, 49.1,

A. Banerjee et al. / Tetrahedron 69 (2013) 9096e9104
9103
13C NMR (100 MHz, CDCl3):
114.0, 66.3, 48.5; Anal. Calcd for C11H11N2OSBr: C, 44.16; H, 3.71; N,
9.36; found C, 44.20; H, 3.72; N, 9.29.
d
169.1, 151.6, 132.4, 129.4, 123.3, 120.5,
150.6, 136.9, 126.9, 125.7, 120.4, 119.1, 66.4, 48.7, 35.6, 34.1, 22.5,
14.1; HRMS (ESI) calcd for C15H20N2OS (MþHþ) 277.1369, found
277.1370.
4.3. General procedure for preparation of substituted
2-morpholinobenzo[d]thiazole (8e14) (a0eb0) from
substituted N-(phenyl) morpholine-4-carbothioamide
(8e14) using Pd(OAc)2 and 1,10-phenanthroline
4.3.4. 6-Butyl-2-(piperidin-1-yl)benzo[d]thiazole (9b0). The general
procedure was followed. The product was purified by column
chromatography (10% EtOAc/hexane) to give the title compound
9b0 (241 mg, 88%) as liquid; Rf (10% EtOAc/hexane) 0.28; nmax (KBr):
2932, 2855, 1602, 1566, 1535, 1463, 1448, 1383, 1354, 1338, 1291,
1261, 1243, 1210, 1200, 1125, 1014, 934, 852, 818, 684 cmꢂ1; 1H NMR
Substituted phenyl isothiocyanate (8e14) (1.5 mmol) was
reacted with morpholine a (1.5 mmol) under solvent free condition
and immediate formation of the corresponding thiourea was ob-
served. To this in situ generated thiourea DMF (2 mL) was added
and medium was stirred at room temperature for 5 min followed by
the addition of K2CO3 (1.5 mmol), 1,10-phenanthroline (5 mol %)
and palladium acetate (2 mol %). Then the reaction mixture was
subjected to reflux in a preheated oil bath at 85 ꢀC and the progress
of the reaction was monitored by TLC. After the completion of the
reaction the reaction mixture was admixed with water (1 mL) and
the product was extracted with ethyl acetate (2ꢁ10 mL). The or-
ganic layer was dried over anhydrous sodium sulfate (Na2SO4),
filtered and evaporated under reduced pressure. The crude product
so obtained was further purified through silica gel column chro-
matograph (hexane/ethyl acetate, 9:1) to yield the pure substituted
2-morpholinobenzo[d]thiazole (8e14) (a0eb0). The identity and
purity of the product was further confirmed by spectroscopic
analysis.
(400 MHz, CDCl3):
d
7.37 (d, 1H, J¼8.0 Hz, Ar. CeH), 7.38 (s, 1H, Ar.
CeH), 7.08 (d,1H, Ar. CeH), 3.56 (s, 4H, aliphaticeCH2e), 2.62 (t, 2H,
J¼7.6 Hz, aliphaticeCH2e), 1.65 (s, 6H, aliphaticeCH2e), 1.62e1.56
(m, 2H, aliphaticeCH2e), 1.37e1.26 (m, 3H, aliphaticeCH3),
0.93e0.86 (m, 2H, aliphaticeCH2e); 13C NMR (100 MHz, CDCl3):
d
168.7, 151.0, 136.2, 130.8, 126.6, 120.2, 118.5, 49.8, 35.6, 34.2, 25.4,
24.4, 22.5, 14.1; HRMS (ESI) calcd for C16H22N2S (MþHþ) 275.1576,
found 275.1576.
4.3.5. 4-(4,6-Dimethylbenzo[d]thiazol-2-yl)morpholine (10a0). Both
general procedures were followed. The product was purified by
column chromatography (10% EtOAc/hexane) to give the title
compound 10a0 (203 mg, 82%) (228 mg, 92%) as white solid; Rf (10%
EtOAc/hexane) 0.25; mp 116 ꢀC; nmax (KBr): 2956, 2910, 2850, 1580,
1545, 1450, 1376, 1342, 1288, 1233, 1111, 1035, 947, 914, 833 cmꢂ1
;
1H NMR (400 MHz, CDCl3):
d 7.23 (s, 1H, Ar. CeH), 6.92 (s, 1H, Ar.
CeH), 3.78e3.77 (m, 4H, aliphaticeCH2e), 3.56e3.55 (m, 4H,
aliphaticeCH2e), 2.52 (s, 3H, AreCH3), 2.34 (s, 3H, AreCH3); 13C
4.3.1. 4-(6-Methylbenzo[d]thiazol-2-yl)morpholine (8a0). Both gen-
eral procedures were followed. The product was purified by column
chromatography (10% EtOAc/hexane) to give the title compound 8a0
(189 mg, 81%) (212 mg, 91%) as white solid; Rf (10% EtOAc/hexane)
0.26; mp 135 ꢀC; nmax (KBr): 2963, 2912, 2856, 1599, 1575, 1544,
NMR (100 MHz, CDCl3): d 167.6, 149.6, 131.3, 130.6, 128.9, 128.2,
118.3, 66.4, 48.6, 21.3, 18.3; HRMS (ESI) calcd for C13H16N2OS
(MþHþ) 249.1056, found 249.1052.
4.3.6. 4,6-Dimethyl-2-(piperidin-1-yl)benzo[d]thiazole (10b0). The
general procedure was followed. The product was purified by col-
umn chromatography (10% EtOAc/hexane) to give the title com-
pound 10b0 (224 mg, 91%) as white solid; Rf (10% EtOAc/hexane)
0.29; mp 100 ꢀC; nmax (KBr): 2989, 2932, 2848, 1727, 1579, 1538,
1462, 1447, 1434, 1384, 1340, 1287, 1266, 1247, 1212, 1122, 1015, 851,
1464, 1434, 1352, 1281, 1235, 1113, 1026, 943, 811 cmꢂ1
(400 MHz, CDCl3):
;
1H NMR
d
7.44 (d, 1H, J¼8.0 Hz, Ar. CeH), 7.40 (s, 1H, Ar.
CeH), 7.09 (d, 1H, J¼8.0 Hz, Ar. CeH), 3.79 (t, 4H, J¼4.8 Hz,
aliphaticeCH2e), 3.56 (t, 4H, J¼4.8 Hz, aliphaticeCH2e), 2.37 (s, 3H,
AreCH3); 13C NMR (100 MHz, CDCl3):
d 168.6, 150.4, 131.6, 130.7,
127.4, 120.9, 119.0, 66.3, 48.6, 21.3; HRMS (ESI) calcd for C12H14N2OS
639 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d 7.20 (s,1H, Ar. CeH), 6.89 (s,
(MþHþ) 235.09, found 235.09.
1H, Ar. CeH), 3.54 (s, 4H, aliphaticeCH2e), 2.52 (s, 3H, AreCH3),
2.32 (s, 3H, AreCH3), 1.64 (s, 6H, aliphaticeCH2e); 13C NMR
4.3.2. 6-Methyl-2-(piperidin-1-yl)benzo[d]thiazole (8b0). The gen-
eral procedure was followed. The product was purified by column
chromatography (10% EtOAc/hexane) to give the title compound
8b0 (213 mg, 92%) as white solid; Rf (10% EtOAc/hexane) 0.25; mp
106 ꢀC; nmax (KBr): 2942, 2851, 2730, 1604, 1571, 1541, 1463, 1441,
(100 MHz, CDCl3): d 167.7, 149.9, 130.7, 130.5, 128.3, 127.9, 118.2,
49.6, 25.4, 24.5, 21.3, 18.3; HRMS (ESI) calcd for C14H18N2S (MþHþ)
247.1263, found 247.1261.
4.3.7. 4-(5,6-Dimethylbenzo[d]thiazol-2-yl)morpholine (11a0). The
general procedure was followed. The product was purified by col-
umn chromatography (10% EtOAc/hexane) to give the title com-
pound 11a0 (211 mg, 85%) as white solid; Rf (10% EtOAc/hexane)
0.24; mp 131 ꢀC; nmax (KBr): 2966, 2921, 2856, 1607, 1531, 1444,
1384, 1358, 1337, 1265, 1243, 1206, 1121, 1009, 810, 626 cmꢂ1
;
1H
NMR (400 MHz, CDCl3):
d
7.42 (d, 1H, J¼8.0 Hz, Ar. CeH), 7.37 (s, 1H,
Ar. CeH), 7.07 (d, 1H, J¼8.4 Hz, Ar. CeH), 3.56 (s, 4H,
aliphaticeCH2e), 2.37 (s, 3H, AreCH3),1.67 (s, 6H, aliphaticeCH2e);
13C NMR (100 MHz, CDCl3):
d
168.6, 150.9, 130.9, 127.1, 120.8, 118.6,
1375, 1342, 1283, 1262, 1227, 1114, 1069, 1021, 899, 858, 800 cmꢂ1
;
49.7, 25.4, 24.4, 21.3; HRMS (ESI) calcd for C13H16N2S (MþHþ)
1H NMR (400 MHz, CDCl3):
d 7.37 (s, 2H, Ar. CeH), 3.83 (t, 4H,
233.1107, found 233.1104.
J¼4.8 Hz, aliphaticeCH2e), 3.59 (t, 4H, J¼4.8 Hz, aliphaticeCH2e),
2.31 (s, 3H, AreCH3), 2.29 (s, 3H, AreCH3); 13C NMR (100 MHz,
4.3.3. 4-(6-Butylbenzo[d]thiazol-2-yl)morpholine (9a0). Both gen-
eral procedures were followed. The product was purified by column
chromatography (10% EtOAc/hexane) to give the title compound 9a0
(229 mg, 83%) (251 mg, 91%) as white solid; Rf (10% EtOAc/hexane)
0.28; mp 53 ꢀC; nmax (KBr): 2954, 2921, 2856, 2095,1731,1604,1564,
1536, 1461, 1376, 1340, 1277, 1231, 1111, 1071, 1032, 944, 916, 878,
CDCl3): d 167.7, 151.1, 135.1, 130.8, 128.0, 121.3, 120.3, 66.5, 48.7, 20.3,
19.9; HRMS (ESI) calcd for C13H16N2OS (MþHþ) 249.1056, found
249.1059.
4.3.8. 5,6-Dimethyl-2-(piperidin-1-yl)benzo[d]thiazole (11b0). The
general procedure was followed. The product was purified by col-
umn chromatography (10% EtOAc/hexane) to give the title com-
pound 11b0 (214 mg, 87%) as white solid; Rf (10% EtOAc/hexane)
0.26; mp 120 ꢀC; nmax (KBr): 2935, 2853, 1611, 1536, 1444, 1337,
1285, 1248, 1215, 1122, 1008, 989, 864, 796, 683, 635, 608 cmꢂ1; 1H
822, 658 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d
7.48 (d, 1H, J¼8.4 Hz,
Ar. CeH), 7.42 (s, 1H, Ar. CeH), 7.11e7.13 (m, 1H, Ar. CeH), 3.82 (t,
4H, J¼4.8 Hz, aliphaticeCH2e), 3.59 (t, 4H, J¼5.0 Hz,
aliphaticeCH2e), 2.64 (t, 2H, J¼7.6 Hz, aliphaticeCH2e), 1.65e1.54
(m, 2H, aliphaticeCH2e), 1.40e1.29 (m, 2H, aliphaticeCH2e), 0.92
NMR (400 MHz, CDCl3):
d 7.34 (s, 1H, Ar. CeH), 7.32 (s, 1H, Ar. CeH),
(t, 3H, J¼7.4 Hz, aliphaticeCH3); 13C NMR (100 MHz, CDCl3):
d 168.7,
3.55 (s, 4H, aliphaticeCH2e), 2.28 (s, 6H, AreCH3), 1.66 (s, 6H,

9104
A. Banerjee et al. / Tetrahedron 69 (2013) 9096e9104
aliphaticeCH2e); 13C NMR (100 MHz, CDCl3):
d
168.8, 151.5, 134.7,
column chromatography (10% EtOAc/hexane) to give the title
130.0, 128.0, 121.1, 119.8, 49.8, 25.5, 24.5, 20.3, 19.9; HRMS (ESI)
compound 14a0 (112 mg, 45%) as white solid; Rf (10% EtOAc/hexane)
0.11; mp 134 ꢀC; nmax (KBr): 3065, 2934, 2856, 1739, 1595, 1544,
1477, 1440, 1421, 1378, 1326, 1289, 1268, 1227, 1182, 1113, 1045, 943,
calcd for C14H18N2S (MþHþ) 247.1263, found 247.1262.
4.3.9. 4-(6-Methoxybenzo[d]thiazol-2-yl)morpholine
(12a0). The
915, 861, 762, 731 cmꢂ1 1H NMR (400 MHz, CDCl3):
; d 7.23 (d, 1H,
general procedure was followed. The product was purified by col-
umn chromatography (10% EtOAc/hexane) to give the title com-
pound 12a0 (225 mg, 90%) as white solid; Rf (10% EtOAc/hexane)
0.17; mp 134 ꢀC; nmax (KBr): 3065, 2945, 2849, 1600, 1576, 1548,
1475, 1440, 1376, 1341, 1265, 1235, 1182, 1112, 1072, 1058, 1026, 952,
J¼8.0 Hz, Ar. CeH), 7.06 (t, 1H, J¼8.0 Hz, Ar. CeH), 6.82 (d, 1H,
J¼8.0 Hz, Ar. CeH), 3.97 (s, 3H, AreOCH3), 3.81 (t, 4H, J¼5.0 Hz,
aliphaticeCH2e), 3.63 (t, 4H, J¼4.8 Hz, aliphaticeCH2e); 13C NMR
(100 MHz, CDCl3):
d 168.4, 150.8, 142.0, 131.7, 122.4, 113.3, 107.3,
66.4, 55.9, 48.6; HRMS (ESI) calcd for C12H14N2O2S (MþHþ)
914, 835, 811, 652 cmꢂ1
;
1H NMR (400 MHz, CDCl3):
d
7.48 (d, 1H,
251.0849, found 251.0850.
J¼8.8 Hz, Ar. CeH), 7.15 (s, 1H, Ar. CeH), 6.91 (d, 1H, J¼8.8 Hz, Ar.
CeH), 3.81 (s, 7H, AreOCH3þaliphaticeCH2e), 3.56 (t, 4H, J¼4.8 Hz,
Acknowledgements
aliphaticeCH2e); 13C NMR (100 MHz, CDCl3):
d 167.8, 155.4, 146.8,
131.7, 119.9, 113.9, 105.4, 66.4, 56.0, 48.7; HRMS (ESI) calcd for
C
We are grateful to the Department of Science and Technology
(DST) (SR/S1/OC-79/2009) and Council of Scientific and Industrial
Research (CSIR) [02(0096)/12/EMR-II] for funding. A.B., S.K.S., and
S.K.R. thank the CSIR for fellowships. Thanks are also due to CIF, IIT
Guwahati for Mass and NMR spectra.
12H14N2O2S (MþHþ) 251.0849, found 251.0845.
4.3.10. 6-Methoxy-2-(piperidin-1-yl) benzo[d]thiazole (12b0). The
general procedure was followed. The product was purified by col-
umn chromatography (10% EtOAc/hexane) to give the title com-
pound 12b0 (220 mg, 89%) as white solid; Rf (10% EtOAc/hexane)
0.18; mp 72 ꢀC; nmax (KBr): 3054, 2935, 2854, 1599, 1566,1533, 1461,
1448, 1381, 1363, 1333, 1251, 1221, 1123, 1026, 952, 914, 835, 811,
Supplementary data
Copies of 1H and 13C NMR and HRMS spectra of products are
available. Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.tet.2013.08.025.
652 cmꢂ1
;
1H NMR (400 MHz, CDCl3):
d
7.44 (d, 1H, J¼8.8 Hz, Ar.
CeH), 7.13 (s, 1H, Ar. CeH), 6.88 (d, 1H, J¼2.8 Hz, Ar. CeH), 3.80 (s,
3H, AreOCH3), 3.54 (s, 4H, aliphaticeCH2e), 1.67 (s, 6H,
aliphaticeCH2e); 13C NMR (100 MHz, CDCl3):
d 167.9, 155.0, 147.3,
References and notes
131.8, 119.4, 113.6, 105.5, 56.1, 49.8, 25.5, 24.5; HRMS (ESI) calcd for
C
13H16N2OS (MþHþ) 249.1056, found 249.1053.
1. (a) Jordan, A. D.; Luo, C.; Reitz, A. B. J. Org. Chem. 2003, 68, 8693; (b) Le, Z.-G.;
Xu, J.-P.; Rao, H.-Y.; Ying, M. J. Heterocycl. Chem. 2006, 43, 1123.
2. (a) Yella, R.; Murru, S.; Ali, A. R.; Patel, B. K. Org. Biomol. Chem. 2010, 8, 3389; (b)
Yella, R.; Patel, B. K. J. Comb. Chem. 2010, 12, 754.
4.3.11. 4-(6-Butoxybenzo[d]thiazol-2-yl)morpholine
(13a0). The
general procedure was followed. The product was purified by col-
umn chromatography (10% EtOAc/hexane) to give the title com-
pound 13a0 (263 mg, 90%) as white solid; Rf (10% EtOAc/hexane)
0.19; mp 85 ꢀC; nmax (KBr): 2965, 2939, 2876, 2843,1596,1567,1537,
1462, 1451,1398, 1371,1338,1326,1286,1260,1227, 1179, 1112,1060,
1040, 1007, 946, 922, 854, 826, 812, 740 cmꢂ1; 1H NMR (400 MHz,
3. Sahoo, S. K.; Khatun, N.; Gogoi, A.; Deb, A.; Patel, B. K. RSC Adv. 2013, 3, 438.
4. Khatun, N.; Jamir, L.; Ganesh, M.; Patel, B. K. RSC Adv. 2012, 2, 11557.
5. Rout, S. K.; Guin, S.; Nath, J.; Patel, B. K. Green Chem. 2012, 14, 2491.
6. Sahoo, S. K.; Banerjee, A.; Chakraborty, S.; Patel, B. K. ACS Catal. 2012, 2, 544.
7. (a) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42, 1074; (b)
Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 6790;
(c) Shuai, Q.; Deng, G.; Chua, Z.; Bohle, D. S.; Li, C.-J. Adv. Synth. Catal. 2010, 352,
632; (d) Zhao, H.; Wang, M.; Su, W.; Hong, M. Adv. Synth. Catal. 2010, 352, 1301;
(e) Barman, D. N.; Nicholas, K. M. Eur. J. Org. Chem. 2011, 908; (f) John, A.;
Nicholas, K. M. J. Org. Chem. 2011, 76, 4158; (g) Brasche, G.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2008, 47, 1932; (h) Neufeldt, S. R.; Sanford, M. S. Acc. Chem.
Res. 2012, 45, 936; (i) Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596.
8. (a) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48,
5094; (b) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147; (c) Li, J. J.;
Gribble, G. W. Palladium in Heterocyclic Chemistry; Pergamon: New York; (d)
Balme, G.; Bossharth, E.; Monteiro, N. Eur. J. Org. Chem. 2003, 4101; (e) Zeni, G.;
Larock, R. C. Chem. Rev. 2006, 106, 4644.
CDCl3):
d
7.47 (d, 1H, J¼8.8 Hz, Ar. CeH), 7.14 (s, 1H, Ar. CeH), 6.90
(d,1H, J¼2.8, Ar. CeH), 3.94 (t, 2H, J¼6.6 Hz, AreOCH2e), 3.80 (t, 4H,
J¼4.8 Hz, aliphaticeCH2e), 3.54 (t, 4H, J¼5.0 Hz, aliphaticeCH2e),
1.78e1.72 (m, 2H, aliphaticeCH2e), 1.53e1.44 (m, 2H,
aliphaticeCH2e), 0.99e0.95 (t, 3H, J¼7.4 Hz, aliphaticeCH3); 13C
NMR (100 MHz, CDCl3):
d 167.7, 154.8, 146.6, 131.6, 119.8, 114.4,
106.0, 68.5, 66.3, 48.6, 31.5, 19.3, 14.0; HRMS (ESI) calcd for
C
15H22N2O2S (MþHþ) 293.1318, found 293.1320.
9. Joyce, L. L.; Batey, R. A. Org. Lett. 2009, 11, 2792.
10. (a) Inamoto, K.; Hasegawa, C.; Hiroya, K.; Doi, T. Org. Lett. 2008, 10, 5147; (b)
Inamoto, K.; Hasegawa, C.; Kawasaki, J.; Hiroya, K.; Doi, T. Adv. Synth. Catal.
2010, 352, 2643.
4.3.12. 6-Butoxy-2-(piperidin-1-yl) benzo[d]thiazole (13b0). The
general procedure was followed. The product was purified by col-
umn chromatography (10% EtOAc/hexane) to give the title com-
pound 13b0 (258 mg, 89%) as white solid; Rf (10% EtOAc/hexane)
0.20; mp 68 ꢀC; nmax (KBr): 3079, 2928, 2858, 1722, 1606, 1540,
1462, 1449, 1368, 1338, 1285, 1246, 1209, 1124, 1058, 1013, 933, 860,
11. Wang, H.; Wang, L.; Shang, J.; Li, X.; Wang, H.; Gui, J.; Lei, A. Chem. Commun.
2012, 76.
12. Brasche, G.; Buchwald, S. L. Angew. Chem. 2008, 120, 1958 Angew. Chem., Int. Ed.
2008, 47, 1932.
13. (a) Ueda, S.; Nagasawa, H. Angew. Chem., Int. Ed. 2008, 47, 6411; (b) Ueda, S.;
Nagasawa, H. J. Org. Chem. 2009, 74, 4272; (c) King, A. E.; Huffman, L. M.; Ca-
sitas, A.; Costas, M.; Ribas, X.; Stahl, S. S. J. Am. Chem. Soc. 2010, 132, 12068; (d)
Tang, S.; Gong, T.; Fu, Y. Sci. China: Chem. 2013, 56, 619.
14. Guin, S.; Ghosh, T.; Rout, S. K.; Banerjee, A.; Patel, B. K. Org. Lett. 2011, 13, 5976.
15. (a) Tang, S. Y.; Guo, Q. X.; Fu, Y. Chem.dEur. J. 2011, 17, 13866; (b) Wasa, M.;
Chan, K. S. L.; Zhang, X.-G.; He, J.; Miura, M.; Yu, J.-Q. J. Am. Chem. Soc. 2012, 134,
18570; (c) Engle, K. M.; Thuy-Boun, P. S.; Dang, M.; Yu, J.-Q. J. Am. Chem. Soc.
2011, 133, 18183; (d) Wasa, M.; Engle, K. M.; Lin, D. W.; Yoo, E. J.; Yu, J.-Q. J. Am.
Chem. Soc. 2011, 133, 19598; (e) Dai, H.-X.; Yu, J.-Q. J. Am. Chem. Soc. 2012, 134,
134; (f) Cross, W. B.; Hope, E. G.; Lin, Y.-H.; Macgregor, S. A.; Singh, K.; Solan, G.
A.; Yahya, N. Chem. Commun. 2013, 1918; (g) Schoenebeck, F.; Houk, K. N. J. Am.
Chem. Soc. 2010, 132, 2496; (h) Campbell, A. N.; Meyer, E. B.; Stahl, S. S. Chem.
Commun. 2011, 10257.
799, 642 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d
7.42 (d, 1H, J¼8.8, Ar.
CeH), 7.12 (s, 1H, Ar. CeH), 6.87 (d, 1H, J¼2.6 Hz, Ar. CeH), 3.93 (t,
2H, J¼6.4 Hz, AreOCH2e), 3.52 (s, 4H, aliphaticeCH2e), 1.71e1.76
(m, 2H, aliphaticeCH2e), 1.65 (s, 6H, aliphaticeCH2e), 1.45e1.51
(m, 2H, aliphaticeCH2e), 0.97 (t, 3H, J¼7.4 Hz, aliphaticeCH3); 13
C
NMR (100 MHz, CDCl3): d 167.6, 154.4, 147.1, 131.7, 119.3, 114.2, 106.1,
68.6, 49.7, 31.6, 25.4, 24.4, 19.4, 14.0; HRMS (ESI) calcd for
C
16H22N2OS (MþHþ) 291.0849, found 291.0846.
4.3.13. 4-(4-Methoxybenzo[d]thiazol-2-yl)morpholine
general procedure was followed. The product was purified by
(14a0). The
16. (a) Khoobi, M.; Alipour, M.; Zarei, S.; Jafarpour, F.; Shafiee, A. Chem. Commun.
2012, 2985; (b) Ye, M.; Gao, G.-L.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133, 6964.