The [Cu]-catalyzed SNAR reactions: Direct amination of electron deficient aryl halides with sodium azide and the synthesis of arylthioethers under Cu(II) - Ascorbate redox system

Article abstract of DOI:10.1016/j.tet.2010.07.032

A one pot [Cu]-promoted S_NAr reaction of electron-deficient halobenzenes with sodium azide and the reduction of the intermediate aryl azides under the same Cu(II)-ascorbate redox conditions leading to anilines has been documented. Control experiments revealed that both ascorbate and proline play important role in the reaction path way. Further, the use of this catalytic Cu(II)-ascorbate redox system has been explored for the synthesis of arylthioethers.

Full text of DOI:10.1016/j.tet.2010.07.032

Tetrahedron 66 (2010) 7642e7650
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The [Cu]-catalyzed SNAR reactions: direct amination of electron deficient
aryl halides with sodium azide and the synthesis of arylthioethers under
Cu(II)eascorbate redox system
*
Yogesh Goriya, C.V. Ramana
National Chemical Laboratory (CSIR, India), Division of Organic Chemistry, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 June 2010
Received in revised form 9 July 2010
Accepted 12 July 2010
Available online 21 July 2010
A one pot [Cu]-promoted SNAr reaction of electron-deficient halobenzenes with sodium azide and the
reduction of the intermediate aryl azides under the same Cu(II)eascorbate redox conditions leading to
anilines has been documented. Control experiments revealed that both ascorbate and proline play im-
portant role in the reaction path way. Further, the use of this catalytic Cu(II)eascorbate redox system has
been explored for the synthesis of arylthioethers.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
SNAr reaction
Cu(II)eascorbate redox system
Azide reduction
Thioether
Anilines
1. Introduction
2. Results and discussion
The recent discovery of the Meldal1 and Sharpless2 groups re-
vealing the dramatic rate acceleration of the azide-alkyne cyclo-
addition3 under copper(I) catalysis (CuAAC) has extended this
reaction to many branches of chemistry ranging from bio- to ma-
terials and polymers and is often referred as ‘the click reaction’.4
The inaugural protocol that employ the Cu(II) salts with ascorbate
is the method of choice for preparative synthesis of 1,2,3-triazoles,1
though there are several other mild alternatives that have been
disclosed especially dealing with the bio-conjugations.5 In recent
publications, we showed that under the classical Cu(II)eascorbate
redox system, the 1,4-diaryltriazoles can be prepared in one-pot
from SNAr of o- and p-fluoronitrobenzenes with NaN3 and sub-
sequent Huisgen [3þ2] cycloaddition of intermediate aryl azides
with various alkynes, being both the SNAr and [3þ2] cycloaddition
are promoted by Cu(II)eascorbate redox system.6 In this manu-
script we document the direct amination of the electron deficient
aryl halides using sodium azide as the amine source7 and also the
thiolation8 with alkyl/aryl/heteroaryl thiols under the classical Cu
(II)eascorbate redox system, the first one being an unintended
observation.
2.1. Amination employing azide as ammonia surrogate
As a part of our ongoing studies dealing with the synthesis
and structural analysis of isomeric halo-nitro derivatives of
diphenyl-1,2,3-triazoles,6b the SNAreclick reaction of o-/p-nitro-
fluorobenzenes with 4-fluorophenyacetlylene (3a) was attempted
(Scheme 1). Interestingly, the 2-aminonitrobenzene (5a) was
obtained as the major product. This might be resulting from the
competitive reduction of the intermediate aryl azide.9 Intrigued by
this, the three isomeric fluoronitrobenzenes (1aec) were subjected
to these conditions. The SNAr followed by azide reduction was found
to be facile with the 2- and 4-fluoronitrobenzenes (1a and 1c) and
the 3-fluoronitrobenzene (1b) was intact under these conditions.
When the corresponding three isomeric azidonitrobenzenes (2aec)
Scheme 1. Reagents and conditions: (a) 1.2 equiv NaN3, CuSO4 (20 mol %), Naeascorbate
(15 mol %), L-proline (20 mol %), Na2CO3 (20 mol %), DMSO/H2O (9:1), 65e70 ꢀC, 24 h; (b)
for entries 2aed conditions are same as above without NaN3.
* Corresponding author. Tel.: þ91 20 25902577; fax: þ91 20 25902629; e-mail
address: vr.chepuri@ncl.res.in (C.V. Ramana).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.07.032

Y. Goriya, C.V. Ramana / Tetrahedron 66 (2010) 7642e7650
Table 1 (continued)
7643
Entry
Reactants
Conditions
Yield
Entry
Substrate
Product
Yield (%)
Triazole 4
Aniline 5 (%)
1
2
3
4
5
6
7
8
9
1a
1a
2a
2a
2b
2c
2a
2b
2c
3b
3a
3b
3a
3b
3a
e
a
a
b
b
b
b
a
a
a
d
d
d
d
23%
13%
e
55
57
57
63
52
65
67%
61%
68%
10
57
72
11
12
e
e
e
e
76
were employed, all the three isomers gave the corresponding
nitroanilines in good yields. This indicated that a nominal de-
activation is required for the azide reduction when compared to
that of SNAr. As a control, the simple aryl halides were subjected for
the one pot ‘SNAreazide reduction’. The F-/Cl-/Br-benzenes were
intact under these conditions and the iodobenzene was smoothly
converted to azidobenzene (71%).10 Under similar conditions, the o-
chloronitrobenzene, p-bromo nitrobenzene, and also the corre-
sponding iodonitrobenzenes gave the corresponding nitroanilines
in comparable yields (Table 1, entries 1e5).7
13
14
78
73
Table 1
15
24
The scope of one-pot amination reaction of aryl halide with NaN3 under Cu(II)e
ascorbate redox system
16
17
42
68
Entry
1
Substrate
Product
Yield (%)
74
18
19
49
71
2
3
76
76
20
21
53
71
4
5
86
77
22
23
28
6
7
67
69
No reaction
No reaction
d
24
25
d
8
9
54
68
32
26
No reaction
d

7644
Y. Goriya, C.V. Ramana / Tetrahedron 66 (2010) 7642e7650
A literature search has revealed a recent report on azide to amine
conversion under the Cu(II)eascorbate redox system.11 Peng and co-
workers observed the reduction of a triazolyl azide during the CuAAC
reaction[sodium ascorbate(0.5 equiv)and coppersulfate(0.15 equiv)
inTHF/water and heating at 70 ꢀC (oil bath)]. The reduction in general
wasdictatedbytheazidepositioning. Sinceboththeazidationandthe
reduction are promoted under the similar conditions we have
intended to further extend our observation in the direction of syn-
thesis of anilines using sodium azide as amine source.12,13a,13b
Initial experiments on the reduction of 4-azidonitrobenzene
employing all the components individually have revealed that the
ascorbate could facilitate the reduction alone albeit it was required
in stoichiometric amounts (1 equiv ascorbate, 2 h, 99% conversion,
94% isolated yield, Fig.1a). Next we studied the azide reduction with
ascorbate in the presence of CuSO4 (1e20 mol % of each, Fig.1b). The
reductionwas sluggishand the reactions wereincomplete even after
24 h heating. Next we have introduced a fixed amount of base and
concentrations of Cu(II)eascorbate salt werevaried. As it can be seen
from the Figure 1c, there was an improvement however is not sub-
stantial. The role of proline has been examined subsequently. The
reactions were carried out with varying concentrations of Cu(II)e
sodium ascorbate with fixed concentrations of base and proline
(20 mol % each). The results were exciting even with 1 mol % of Cu
(II)eascorbate redox system, the reactions were close to completion
within 12 h (99% conversion 84% isolated yield). Thus these
selectively occurred at ortho-position to the nitro group via fluorine
displacement (Table 1, entry 7), whereas 2-nitro-4-fluo-
roiodobenzene gave mainly the 2-nitro-4-fluoroaniline with a net
displacement of iodo group (Table 1, entry 6). The ‘SNAreazide re-
duction’ is also facile with hetero-aromatic halides, such as 4-
chloro-3-nitro-coumarin and 7-bromo-2H-benzo[b][1,4]thiazin-3
(4H)-one (Table 1, entries 12 and 14). With 6-bromo-2H-benzo[b]
[1,4]oxazin-3(4H)-one, the corresponding azide was isolated in
good yields (Table 1, entry 17). With regard to the reaction of benzyl
halides under these conditionsdbenzyl bromide gave exclusively
the benzyl azide (57%), 4-nitrobenzyl bromide gave the 4-nitro-
benzaldehyde (32%) and unidentified complex mixture indicating
the competitive halide hydrolysis and subsequent oxidation
(Table 1, entries18 and 22). The O-mesylates were found to be hy-
drolyzed under these conditions (Table 1, entry 21).
The isolation of the intact aryl azides from iodobenzene (Table 1,
entry 19) and from p-alkoxy substituted derivatives (Table 1, entries
17 and 20) indicate that the Cu(I)-mediated decomposition of the
azide group depends upon relative electrophilicity of the azide
group, which is controlled by the nature of the aryl substituent.15 It
has been proposed earlier that aryl azides exist in two octet reso-
nance structures of the azide groupdforms I and II (Fig. 2), amongst
which the former is predominant when the p-substituent is an
electronic withdrawing group.16 Therefore, with the available in-
formation, we propose that under the present conditions,
Figure 1. Control experiments revealing the effect of various additives on the outcome of the 4-azidonitrobenze reduction (conversion to nitroaniline estimated by GC).
experiments revealed that presence of ascorbate is essential and
that the rate of the reaction is enhanced by the presence of the Cu
(II)esalt and proline and that proline is playing an important role.
The stabilization of Cu(I)especies by proline has been proposed in
the mechanism given for the CuAAC reactions.14
a preferential azide decomposition occurs via form I, where the
doublebond character of the fissile NeN2 bond is decreased and the
entropy of activation for the rupture of this bond is lowered with
the electron withdrawing substituents.15 Further studies to un-
derstand the detailed mechanism of the reaction are in progress.
The scope of the one pot azidationereduction reaction was ex-
amined employing a wide range of deactivated aryl halides. Table 1
shows the generality of the present amination and also the limi-
tations, where the reactions were unsuccessful (Table 1, entries 23,
24, and 26) or resulted in azides (Table 1, entries 17e20) or
sometimes even dehalogenation (Table1, entry 25).
The reactions are facile when the electron withdrawing groups
(nitro or eCF3) are placed either ortho- or para- to the leaving halo
group. For example, the amination of 3-nitro-4-fluoroiodobenzene
Figure 2. Two canonical forms of the aryl azides.

Y. Goriya, C.V. Ramana / Tetrahedron 66 (2010) 7642e7650
7645
2.2. Synthesis of diaryl and alkyl aryl sulfides under classical
‘click reaction’ conditions
The scope of the Cu(I)-promoted thioether synthesis was ex-
amined by employing a set of four aryl halides (1a and 1cee) and
four representative aryl-, heteroaryl-, and alkylthiols (6aed). The
results are given in Table 3. Table 4 presents the thioether synthesis
employing randomly selected aryl and benzyl halides. The reactions
in general are smooth and the corresponding diaryl thioethers are
obtained in good to excellent yields. Remarkably, sterically de-
manding ortho-substituted aryl halides also give good results
without any difficulty (Table 3, entries 1e4 and 13e16). The reaction
of aryl halide containing deactivating groups like eNO2, eCF3,eCN
with aryl and alkyl thiol afford the cross-coupling product in 91e96%
yield in 10e18 h (Table 4). Under these conditions, p-nitrobenzyl
bromide is highly reactive and promotes the desired thioether
within 10 min (Table 4, entries 5 and 6). In addition, the reaction of
pyridine-2-thiol and benzo[d]thiazole-2-thiol with aryl fluorides
were successfully performed to afford the heteroaryl thioethers in
good yields (Table 4, entries 7 and 8). As seen with the azidation,
cross coupling reactions between the deactivated aryl halides and
thiols resulted in good to excellent yields. In contrast the reaction of
p-methoxy iodobenzene gave the coupling product in poor yields
(entry 9, Table 4) and the diaryl disulfide was isolated as the major
product. As noticed earlier with the azidation, the attempted SNAr
reaction of the 3-fluoronitrobenzene (1b) with thiophenol (6a) was
unsuccessful under these conditions and the disulphide was
obtained as the main product.
Encouraged by our observation of the rate enhancement of SNAr
with azide nucleophile under the classical Cu(II)eascorbate redox
system at ambient temperatures and the possibility of azida-
tionecycloaddition and azidationereduction in one pot, we were
further interested in expanding the scope of this ‘click reaction’
catalyst system for the synthesis of the arylthioethers via the SNAr
reaction. The C(aryl)eS bond formation of electron deficient aryl
halides in the presence of strong bases is well documented.17 On
the other hand, various transition metal complexes have been ex-
plored for the C(aryl)eS bond formation employing the aryl io-
dides18 or boronic acids19 as the coupling partners. However, the
use of metal catalysts in the C(aryl)eS bond formation via SNAr is
a much less studied transformation.20
The thiophenol has been employed as the nucleophile for the
initial exploratory experiments. Under the standard conditions
used for the azidation (20 mol % of each Na2CO3, CuSO4, L-proline
and 15 mol % of ascorbate in DMSO at 65e70 ꢀC for 24 h), the re-
action of thiophenol with 4-nitrofluorobenzene gave the corre-
sponding diarylthioether in moderate yields. Formation of
substantial amounts of the diphenyl disulphide was noticed. Opti-
mization of the reaction conditions has been carried out by varying
the concentrations of additives and temperature (Table 2). These
experiments revealed that the concentration of the base has
a substantial effect on the outcome of the reaction. Use of 5 equiv of
base was found to be optimal. The optimized reaction conditions
employ 1.1 equiv of thiol, 5 equiv of base, 10 mol % of each ascor-
3. Conclusion
We document the SNAr reaction of deactivated aryl halides with
azide and thiol for the Cu(II)eascorbate redox system. We found that
the intermediate azides are reduced under the same catalytic con-
ditions and afford the corresponding anilines. One-pot ‘SNAreazide
reduction’ has been generalized as a simple tool for the direct ami-
nation of deactivated aryl halides under the Cu(II)eascorbate cata-
lytic system. Control experiments revealed the essential role of
ascorbate and proline in the present reaction and the course of the
reaction as SNAr with azide proceeding with an in situ reduction of
azidobenzene intermediates. Coming to the thioethers synthesis for
bate, Cu(II), and
excellent yields (99% by GC/97% isolated). Further control experi-
ments revealed that the absence of the ascorbate and -proline has
L-proline in DMSO to give the desired thioether in
L
no substantial effect on the reaction time and on the product yield.
These experiments indicated that the thiol is also acting as a re-
ducing agent for the in situ generation of the active Cu(I)-species.21
Next the effect of reaction temperature was examined. The lower-
ing of the temperature was detrimental and the disulphide for-
mation was found to be a competing reaction.
Table 2
Control experiments for coupling of 4-nitrofluorobenzene with thiophenol
NO.
CuSO4 (mol %)
Naeascorbate (mol %)
L-Proline (mol %)
Na2Co3 (equiv)
Temp.
Yield (%)
1
2
3
4
5
6
7
10
10
10
d
10
10
5
10
10
10
d
d
10
5
10
10
10
d
d
d
d
5
2
5
5
5
5
5
5
5
65e70 ꢀC
78a
71a
97b
62a
97a
85a
98a
97a
rt
65e70 ꢀ
65e70 ꢀ
65e70 ꢀ
65e70 ꢀ
65e70 ꢀ
65e70 ꢀ
C
C
C
C
C
C
8
5
5
a
Based on GC.
Isolated yield.
b

7646
Y. Goriya, C.V. Ramana / Tetrahedron 66 (2010) 7642e7650
Table 3 (continued)
Table 3
Scope of Cu(I)-catalyzed thioether synthesis and the synthesized 4ꢁ4 thioether
Entry
Haloderivative
Thiol
Product
compounds library
10
1d
6b
11
12
13
14
15
1d
1d
1e
1e
1e
6c
6d
6a
6b
6c
Entry
1
Haloderivative
Thiol
Product
1a
6a
2
3
4
5
6
7
8
1a
1a
1a
1c
1c
1c
1c
6b
6c
6d
6a
6b
6c
6d
16
1e
6d
the Cu(II)eascorbate catalytic system, the deactivated aryl halides
underwent SNAr smoothly in case of all the four different thiols
employed. Control experiments reveal that the reaction works
smoothly without ascorbate and L-proline. The thioether formation
with the elector rich aromatic halides was found to be sluggish.
Since that the SNAr reaction of deactivated aryl halides with azide
or thiol are promoted under the same Cu(II)eascorbate redox sys-
tem, and that the azide-alkyne cycloaddition and amine reduction
are also feasible under these catalytic conditions, we believe that the
integration of all these possibilities on designed substrates with
complementary functional groups will provide a platform for de-
veloping multi-component reactionsdsimple means of molecular
complexity generation and small molecules library synthesis.
4. Experimental
4.1. General methods
9
1d
6a
Commercial reagents and solvents were used without purifica-
tion. Column chromatography was carried out by using Spec-
trochem silica gel (100e200 mesh). 1H and 13C NMR spectroscopy

Y. Goriya, C.V. Ramana / Tetrahedron 66 (2010) 7642e7650
7647
Table 4
(oil bath temperature) and then the mixture was poured into 30 mL
of ice-cold water. The solid products were filtered and crystallized
from appropriate solvent systems to procure the anilines/azides.
Liquid products were purified by column chromatography.
Scope of the Cu(I) catalyzed thioether synthesis
Entry
1
Haloderivative
Thiol
Product
4.2.1. 2-Nitroaniline (5a). Yellow solid; Rf (30% EtOAc/pet. ether)
0.5; 1H NMR (CDCl3, 200 MHz):
d
6.06 (br s, 2H), 6.7 (dt, J¼1.3,
C12H25SH
8.4 Hz, 1H), 6.80 (dd, J¼1.2, 8.4 Hz, 1H), 7.35 (dt, J¼1.5, 8.4 Hz, 1H),
8.1 (dd, J¼1.5, 8.6 Hz, 1H) ppm.
4.2.2. 3-Nitroaniline (5b). Yellow solid; Rf (20% EtOAc/pet. ether)
0.2; 1H NMR (CDCl3, 200 MHz):
d
3.98 (br s, 2H), 6.92 (ddd, J¼0.9,
2
3
C12H25SH
2.3, 8.0 Hz, 1H), 7.25 (m, 1H), 7.46 (t, J¼2.2 Hz, 1H), 7.55 (ddd, J¼0.9,
2.2, 8.1 Hz, 1H) ppm.
4.2.3. 4-Nitroaniline (5c). Yellow solid; Rf (20% EtOAc/pet. ether)
0.2; 1H NMR (CDCl3, 200 MHz):
d 4.41(br s, 2H), 6.57e6.65(m, 2H),
8.01e8.09 (m, 2H) ppm.
4
5
C12H25SH
4.2.4. 5-Fluoro-2-nitroaniline (5d). Yellow solid; Rf (30% EtOAc/pet.
ether) 0.4; mp: 74e75 ꢀC; IR (Nujol)
: 3488, 3348, 1641, 1463, 1377,
n
1259, 845, 748 cmꢂ1; 1H NMR (CDCl3, 200 MHz):
d 6.2 (s, 2H), 6.4e6.5
(m, 2H), 8.2 (dd, J¼5.9, 9.3 Hz, 1H) ppm; 13C NMR (CDCl3, 50 MHz):
d
103.6 (d, J¼26.0 Hz),105.7 (d, J¼24.7 Hz),129.3 (d, J¼12.1 Hz),146.7
(q, J¼13.3 Hz), 164.3 (q), 169.4 (q) ppm; ESIMS (m/z) 157.2353 [17%
(Mþ1)þ], 179.1590 [96% (MþNa)þ], 197.2501 [10% (MþK)þ].
4.2.5. 4-Iodo-2-nitroaniline (5e). Yellow solid; Rf (30% EtOAc/pet.
ether) 0.4; mp: 118e119 ꢀC; IR (Nujol)
n: 3520, 3398, 3019, 1619,
6
7
C12H25SH
1508, 1215, 756 cmꢂ1; 1H NMR (CDCl3, 200 MHz):
d
6.1 (s, 2H), 6.6
(d, J¼8.8 Hz, 1H), 7.6 (dd, J¼2.1, 8.8 Hz, 1H), 8.4 (d, J¼2.1 Hz, 1H)
ppm; 13C NMR (CDCl3, 50 MHz):
(d), 143.7 (d), 144.0 (q) ppm.
d 75.8 (q), 120.6 (d), 133.0 (q),134.2
4.2.6. 4-Aminobenzonitrile (5f). Yellow solid; Rf (30% EtOAc/pet.
ether) 0.2; 1H NMR (CDCl3, 200 MHz):
(m, 2H), 7.38e7.44 (m, 2H) ppm.
d 4.21 (br s, 2H), 6.61e6.68
8
9
C12H25SH
4.2.7. 3,5-Bis(trifluoromethyl)aniline (5g). Yellow solid; Rf (20%
EtOAc/pet. ether) 0.2; 1H NMR (CDCl3, 200 MHz):
(s, 2H), 7.64 (m, 1H) ppm.
d 6.27 (s, 2H), 7.43
4.2.8. 4-(Trifluoromethyl)aniline (5h). Yellow solid; Rf (20% EtOAc/
pet. ether) 0.2; 1H NMR (CDCl3, 200 MHz):
6.66e6.70 (m, 2H), 7.36e7.40 (2H) ppm.
d 3.93 (br s, 2H),
measurements were carried out on Bruker AC 200 MHz or Bruker
DRX 400 MHz spectrometers and TMS was used as an internal
standard. 1H and 13C NMR chemical shifts are reported in parts per
million downfield from tetramethylsilane and coupling constants
(J) are reported in Hertz (Hz). The following abbreviations are used
to designate signal multiplicity: s¼singlet, d¼doublet, t¼triplet,
q¼quartet, m¼multiplet, br¼broad. The multiplicity of 13C NMR
signals was assigned with the help of DEPT spectra and the ab-
breviations used: s¼singlet, d¼doublet, t¼triplet, q¼quartet, rep-
resent C (quaternary), CH, CH2, and CH3, respectively. GC analyses
were carried out on Agilent Technologies 7890. Mass spectra were
recorded on API QStar Pulsar (Hybrid Quadrupole-TOF LC/MS/MS)
spectrometer or on Applied Biosystems Voyager-DE STR 4383
(MALDI-TOF). Elemental analysis data were obtained on a Thermo
Finnigan Flash EA 1112 Series CHNS Analyzer.
4.2.9. 4-Nitro-2-(trifluoromethyl)aniline (5i). Yellow solid; Rf (20%
EtOAc/pet. ether) 0.3; 1H NMR (CDCl3, 200 MHz):
4.95 (s, 2H), 6.76
d
(d, J¼9.0 Hz, 1H), 8.17 (dd, J¼2.6, 9.0 Hz, 1H), 8.38 (d, J¼2.5 Hz, 1H)
ppm.
4.2.10. 4-Amino-3-nitro-2H-chromen-2-one (5j). Rf (40% EtOAc/pet.
ether) 0.2; mp: 248e249 ꢀC; IR (Nujol)
n
: 3389, 3294, 1715, 1633,
1462, 1377, 1271, 1107, 769 cmꢂ1
;
1H NMR (DMSO-d6, 200 MHz):
d
7.2 (dd, J¼1.0, 8.3 Hz 1H), 7.3 (dd, J¼1.0, 8.2 Hz 1H), 7.6 (dt, J¼1.2,
7.2 Hz 1H), 8.3 (d, J¼8.2 Hz 1H), 9.5 (s, 2H) ppm; 13C NMR (DMSO-
d6, 50 MHz): d 112.9 (q), 117.0 (d), 124.2 (d), 125.1 (d), 134.9 (d), 151.8
(q), 153.2 (q), 170.2 (q) ppm; ESIMS (m/z) 207.1113 [6% (Mþ1)þ],
229.0860 [100% (MþNa)þ].
4.2. General procedure for azidationereductions
4.2.11. 2-Nitro-4-(trifluoromethyl)aniline (5k). Yellow solid; Rf (20%
EtOAc/pet. ether) 0.3; 1H NMR (CDCl3, 200 MHz):
d 6.38 (s, 2H), 6.91
To a solution of halobenzene (1 equiv) in DMSO/H2O (9:1, 10 mL
for 1 mmol substrate) were added L-proline (0.2 equiv), Na2CO3
(d, J¼8.8 Hz, 1H), 7.56 (dd, J¼2.1, 8.8 Hz, 1H), 8.44 (s, 1H) ppm.
(0.2 equiv), NaN3 (1.2 equiv), sodium ascorbate (0.15 equiv), and
4.2.12. 7-Amino-2H-benzo[b][1,4]thiazin-3(4H)-one (5l). Rf (40%
CuSO4$5H2O (0.2 equiv). The mixture was stirred for 24 h at 70 ꢀC
EtOAc/pet. ether) 0.2; mp: 156e157 ꢀC; IR (Nujol)
n: 3403, 3196,

7648
Y. Goriya, C.V. Ramana / Tetrahedron 66 (2010) 7642e7650
1673, 1608, 1462, 1377, 1245, 814 cmꢂ1
;
1H NMR (DMSO-d6,
Anal. Calcd for C18H29NO2S: C, 66.83; H, 9.04; N, 4.33. Found: C,
200 MHz):
d
3.22 (s, 2H), 4.02 (s, 2H), 6.4 (dd, J¼2.5, 8.5 Hz, 1H), 6.5
66.79; H, 9.11; N, 4.26.
(d, J¼2.4 Hz, 1H), 6.7 (d, J¼8.5 1H), 9.8 (s, 1H) ppm; 13C NMR
(DMSO-d6, 50 MHz):
d
29.6 (t), 112.6 (d), 113.3 (d), 117.9 (d), 119.8
4.3.5. 4-Nitrophenyl phenyl sulfide (7ca)22c. Brown solid; Rf (100%
(q), 127.9 (q), 142.7 (q), 164.4 (q) ppm; ESIMS (m/z) 181.1051 [100%
pet. ether) 0.2; mp: 52e53 ꢀC (lit. 54e55 ꢀC); IR (CHCl3)
n
: 1593,
1H NMR (CDCl3,
7.12e7.19 (m, 2H), 7.43e7.56 (m, 5H), 8.02e8.09 (m,
2H) ppm; 13C NMR (CDCl3, 50 MHz):
124.0 (d, 2C), 126.6 (d, 2C),
(Mþ1)þ], 203.1070 [31% (MþNa)þ], 219.1430 [12% (MþK)þ].
1575, 1475, 1338, 1111, 1083, 1024, 852, 740 cmꢂ1
200 MHz):
;
d
4.2.13. 6-Azido-2H-benzo[b][1,4]oxazin-3(4H)-one (5m). Rf (40%
d
EtOAc/pet. ether) 0.5; mp: 213e215 ꢀC; IR (Nujol)
n
: 2923, 2854,
129.7 (d), 130.0 (d, 2C), 130.3 (s), 134.7 (d, 2C), 145.3 (s), 148.5 (s)
2111, 1683, 1598, 1461, 1377, 1219, 802 cmꢂ1
;
1H NMR (DMSO-d6,
ppm; MALDIeMS (m/z): 232.0432 [Mþ1]D
.
200 MHz):
d
4.6 (s, 2H),6.8 (d, J¼8.6 Hz,1H), 6.9 (d, J¼2.2 Hz,1H), 7.1
(dd, J¼2.2, 8.6 Hz, 1H), 8.6 (s, 1H) ppm; 13C NMR (DMSO-d6,
4.3.6. 2-[(4-Nitrophenyl)sulfanyl]pyridine (7cb)22d. Brown solid; Rf
(15% EtOAc/pet. ether) 0.4; mp: 83e84 ꢀC (lit. 84e85 ꢀC); 1H
50 MHz): d 67.1 (t), 114.6 (q), 118.3 (d), 118.8 (d), 126.9 (d), 142.8 (q),
165.6 (q) ppm.
NMR (CDCl3, 200 MHz):
d
7.18 (ddd, J¼1.1, 4.9, 7.5 Hz, 1H), 7.29
(dt, J¼0.9, 8.0 Hz, 1H), 7.54e7.67 (m, 3H), 8.13e8.20 (m, 2H),
4.3. General procedure for SNAr with thiols
8.50 (d, J¼4.4 Hz, 1H) ppm; 13C NMR (CDCl3, 50 MHz):
d 121.9
(d), 124.0 (d, 2C), 124.8 (d), 131.6 (d, 2C), 137.3 (d), 142.3 (s),
146.7 (s), 150.3 (d), 156.9 (s) ppm; ESIMS (m/z): 233.1128
[Mþ1]þ.
A suspension of halobenzene (1 equiv), L-proline (10 mol %),
Na2CO3 (5 equiv), sodium ascorbate (10 mol %), and CuSO4$5H2O
(10 mol %) in DMSO/H2O (9:1, 10 mL for 1 mmol substrate) was
added neat RSH (1.2 equiv) and contents were heated at 70 ꢀC (oil
bath temperature) with vigorous stirring for 12 h. The reaction
mixture was cooled and partitioned between ethyl acetate and
water. The organic layer was separated and the aqueous layer was
extracted with ethyl acetate. Combined organic layer was washed
with water, brine and dried over anhydrous Na2SO4, and concen-
trated under reduced pressure. The resulting crude product was
purified by either crystallization or by silica gel column
chromatography.
4.3.7. 2-(4-Nitrophenylthio)benzo[d]thiazole (7cc)22b. Yellow solid;
Rf (100% pet. ether) 0.2; mp: 94e95 ꢀC (lit. 95e96 ꢀC); 1H NMR
(CDCl3, 200 MHz):
7.48e7.53 (m, 1H), 7.75e7.80 (m, 2H), 7.94e7.99 (m, 1H), 8.21e8.28
(m, 2H) ppm; 13C NMR (CDCl3, 50 MHz):
121.2 (d), 122.8 (d),
d
7.34e7.38 (m, 1H), 7.43 (dd, J¼1.5, 5.6 Hz, 1H),
d
124.5 (d, 2C), 125.5 (d), 126.6 (d), 132.6 (d, 2C), 136.2 (s), 140.0 (s),
147.8 (s), 153.4 (s), 162.7 (s) ppm; MALDIeMS (m/z): 289.0096
[Mþ1]þ.
4.3.8. 1-Dodecylthio-4-nitrobenzene (7cd)17e. Yellow solid; Rf (100%
4.3.1. 2-Nitrophenyl phenyl sulfide (7aa)22a. Yellow solid; Rf (100%
pet. ether) 0.2; mp: 48e49 ꢀC (lit. 49.5e50.5 ꢀC); IR (CHCl3)
n
: 1595,
1582, 1519, 1460, 1376, 1338, 1182, 1091, 972, 852, 740 cmꢂ1 1H
NMR (CDCl3, 200 MHz):
0.86 (t, J¼6.4 Hz, 3H), 1.24 (br s, 16H),
1.37e1.47 (m, 2H), 1.63e1.74 (m, 2H), 3.0 (t, J¼7.3 Hz, 2H), 7.25e7.33
(m, 2H), 8.07e8.14 (m, 2H) ppm; 13C NMR (CDCl3, 50 MHz):
14.1
pet. ether) 0.3; mp: 73e74 ꢀC; IR (CHCl3)
n
: 1591, 1517, 1474, 1452,
1336, 1304, 1250, 1106, 1042, 853, 753 cmꢂ1 1H NMR (CDCl3,
200 MHz):
6.85 (dd, J¼1.4, 8.1 Hz, 1H), 7.15e7.24 (m, 1H),
7.29e7.37 (m, 1H), 7.44e7.60 (m, 5H), 8.22 (dd, J¼1.6, 8.2 Hz, 1H)
ppm; 13C NMR (CDCl3, 50 MHz):
124.9 (d), 125.7 (d), 128.2 (d),
;
;
d
d
d
d
(q), 22.6 (t), 28.4 (t), 28.8 (t), 29.1 (t), 29.3 (t), 29.4 (t), 29.5 (t), 29.6
(t, 2C), 31.9 (t, 2C), 123.9 (d, 2C), 125.9 (d, 2C), 144.8 (s), 148.2 (s)
ppm; MALDIeMS (m/z): 324.1980 [Mþ1]þ.
130.0 (d), 130.1 (d, 2C), 130.9 (s), 133.4 (d), 135.9 (d, 2C), 139.4 (s),
144.9 (s) ppm; MALDIeMS (m/z): 232.0417 [Mþ1]þ.
4.3.2. 2-[(2-Nitrophenyl)sulfanyl]pyridine (7ab). Yellow solid; Rf
4.3.9. 2-Nitro-4-trifluoromethylphenyl phenyl sulfide (7da)18g
Yellow solid; Rf (100% pet. ether) 0.3; mp: 67e68 ꢀC; IR (CHCl3)
1620, 1562, 1530, 1478, 1441, 1325, 1159, 1086, 910, 753 cmꢂ1 1H
.
n:
(15% EtOAc/pet. ether) 0.2; mp: 74e75 ꢀC; IR (CHCl3)
n
: 1592, 1562,
1463, 1377, 1150, 968, 722 cmꢂ1
;
1H NMR (CDCl3, 200 MHz):
;
d
7.25e7.31 (m, 2H), 7.35e7.47 (m, 1H), 7.41 (dd, J¼1.7, 6.9 Hz, 1H),
NMR (CDCl3, 200 MHz):
d
6.96 (d, J¼8.7 Hz, 1H), 7.52e7.63 (m, 6H),
7.52 (dt, J¼1.0, 7.9 Hz, 1H), 7.73 (dt, J¼1.9, 7.7 Hz, 1H), 8.15 (d, J¼1.7,
8.55 (d, J¼1.6 Hz, 1H) ppm; 13C NMR (CDCl3, 50 MHz):
d 122.9 (d,
8.0 Hz, 1H), 8.59e8.62 (m, 1H) ppm; 13C NMR (CDCl3, 50 MHz):
J¼272.2 Hz), 123.1 (q, J¼4.0 Hz), 127.3 (d, J¼34.5 Hz), 128.9 (d),
129.4 (q, J¼3.4 Hz), 129.7 (s), 130.5 (d, 2C), 130.7 (d), 136.0 (d, 2C),
144.2 (s), 144.6 (s) ppm; ESIMS (m/z): 330.2256 [Mþ1]þ. Anal. Calcd
for C19H28F3NO2S: C, 58.29; H, 7.21; N, 3.58. Found: C, 58.21; H,
7.26; N, 3.53.
d
122.9 (d), 125.4 (d), 126.8 (d), 127.6 (d), 131.6 (d), 133.1 (d), 133.4
(s), 137.6 (d), 147.6 (s), 150.7 (d), 155.4 (s) ppm; ESIMS (m/z):
255.2525 [MþNa]þ.
4.3.3. 2-(2-Nitrophenylthio)benzo[d]thiazole (7ac)22b. Yellow solid;
Rf (100% pet. ether) 0.2; mp: 108e109 ꢀC (lit. 111e113 ꢀC); 1H NMR
(CDCl3, 200 MHz):
7.85e7.90 (m, 1H), 8.06e8.11 (m, 1H), 8.20e8.25 (m, 1H) ppm; 13C
NMR (CDCl3, 50 MHz): 121.6 (d), 123.7 (d), 125.7 (d), 126.3 (d),
4.3.10. 2-Nitro-4-trifluoromethylphenyl
(7db)18g. Yellow solid; Rf (15% EtOAc/pet. ether) 0.3; mp: 91e92 ꢀC
(lit. 90e92 ꢀC); 1H NMR (CDCl3, 200 MHz):
7.30e7.39 (m, 2H),
7.59e7.65 (m, 2H), 7.79 (dt, J¼1.9, 7.7 Hz, 1H), 8.43 (d, J¼1.7 Hz, 1H),
8.64e8.67 (m, 1H) ppm; 13C NMR (CDCl3, 50 MHz):
122.8 (d,
J¼272.3 Hz), 122.9 (q, J¼4.0 Hz), 123.8 (d), 128.7 (d, J¼34.4 Hz),
128.9 (d), 129.3 (q, J¼3.5 Hz), 131.1 (d), 138.1 (d), 146.2 (s), 151.3 (d),
153.8 (s) ppm; MALDIeMS (m/z): 301.0262 [Mþ1]þ.
2-pyridinyl
sulfide
d 7.35e7.46 (m, 3H), 7.48e7.59 (m, 2H),
d
d
126.8 (d), 127.5 (d), 130.7 (d), 133.2 (s), 133.9 (d), 137.6 (s), 146.6 (s),
d
153.6 (s), 160.9 (s) ppm; MALDIeMS (m/z): 289.0117 [Mþ1]þ.
4.3.4. 1-Dodecylthio-2-nitrobenzene (7ad). Yellow solid; Rf (100%
pet. ether) 0.2; mp: 35e36 ꢀC; IR (CHCl3)
n
: 1582, 1460, 1376, 1338,
1091, 852, 722, 740 cmꢂ1
;
1H NMR (CDCl3, 200 MHz):
d
0.88 (t,
4.3.11. 2-((2-Nitro-4-(trifluoromethyl)phenyl)thio)benzo[d]thiazole
(7dc)22e. White solid; Rf (100% pet. ether) 0.3; mp: 80e81 ꢀC; 1H
NMR (CDCl3, 200 MHz): d 7.50e7.54 (m, 2H), 7.57e7.61 (m,1H), 7.67
J¼6.5 Hz, 3H), 1.26 (m, 16H), 1.42e1.48 (m, 2H), 1.67e1.78 (m, 2H),
2.95 (t, J¼7.4, 2H), 7.19 (m, 1H), 7.39e7.43 (m, 1H), 7.51e7.60 (m,
1H), 8.20 (dd, J¼1.4, 8.3 Hz, 1H) ppm; 13C NMR (CDCl3, 50 MHz):
(dd, J¼1.7, 8.6 Hz, 1H), 7.93 (br dd, J¼1.2, 8.1 Hz, 1H), 8.13 (br d,
d
14.1 (q), 22.6 (t), 27.8 (t), 29.1 (t), 29.1 (t), 29.3 (t), 29.4 (t), 29.5 (t),
J¼8.3 Hz,1H), 8.52 (d, J¼1.1 Hz,1H) ppm; 13C NMR (CDCl3, 50 MHz):
29.6 (t, 2c), 31.9 (t), 32.3 (t), 124.2 (d), 126.1 (d), 126.5 (d), 133.3 (d),
d
121.2 (s, CF3), 121.7 (d), 123.1 (q, J¼3.9 Hz), 124.0 (d), 126.8 (d),
138.3 (s), 145.9 (s) ppm; MALDIeMS (m/z): 346.1821 [MþNa]þ.
127.1 (d),129.4 (d, J¼34.7 Hz),130.1 (q, J¼3.3 Hz),130.3 (d),137.8 (s),

Y. Goriya, C.V. Ramana / Tetrahedron 66 (2010) 7642e7650
7649
139.2 (s), 145.3 (s), 153.7 (s), 158.5 (s) ppm; MALDIeMS (m/z):
356.9994 [Mþ1]þ.
(CDCl3, 50 MHz):
d
14.1 (q), 22.6 (t), 27.6 (t), 29.0 (t), 29.1 (t), 29.3 (t),
29.4 (t), 29.5 (t), 29.6 (t, 2C), 31.9 (t), 32.3 (t), 86.4 (s),128.0 (d),134.5
(d), 138.5 (s), 141.9 (d), 146.2 (s) ppm. Anal. Calcd for C18H28INO2S:
C, 48.11; H, 6.28; N, 3.12. Found: C, 48.03; H, 6.36; N, 3.06.
4.3.12. 1-Dodecylthio-2-Nitro-4-trifluoromethylbenzene (7dd). Yel-
low solid; Rf (100% pet. ether) 0.3; mp: 47e48 ꢀC; IR (CHCl3)
n
: 1620,
1561, 1527, 1467, 1329, 1295, 1248, 1181, 1136, 1089, 1056, 911, 828,
759 cmꢂ1; 1H NMR (CDCl3, 200 MHz):
4.3.18. 1-Dodecylthio-4-nitro-2-trifluoromethylbenzene (7gd). Yel-
d
0.86 (t, J¼6.5 Hz, 3H), 1.25
low solid; Rf (100% pet. ether) 0.2; mp: 40e41 ꢀC; IR (CHCl3)
n
: 1605,
1584, 1523, 1465, 1349, 1283, 1174, 1039, 917, 890, 740 cmꢂ1 1H
NMR (CDCl3, 200 MHz):
(br s, 16H), 1.42e1.52 (m, 2H), 1.68e1.83 (m, 2H), 2.98 (t, J¼7.4 Hz,
;
2H), 7.51 (d, J¼6.6 Hz, 1H), 7.72e7.77 (m, 1H), 8.48 (br s, 1H) ppm;
d
0.86 (t, J¼6.5 Hz, 3H), 1.24 (br s, 16H),
13C NMR (CDCl3, 50 MHz):
d
14.1 (q), 22.7 (t), 27.6 (t), 29.0 (t), 29.1
1.43e1.50 (m, 2H), 1.67e1.78 (m, 2H), 3.06 (t, J¼7.4 Hz, 2H), 7.46 (d,
(t), 29.3 (t), 29.4 (t), 29.5 (t), 29.6 (t, 2C), 31.9 (t), 32.4 (t), 123.0 (d,
J¼272.2 Hz), 123.5 (q, J¼4.0 Hz), 126.6 (d, J¼34.7 Hz), 127.0 (d),
129.4 (q, J¼3.3 Hz), 143.6 (s), 145.2 (s) ppm; ESIMS (m/z): 392.1818
[Mþ1]þ. Anal. Calcd for C19H28F3NO2S: C, 58.29; H, 7.21; N, 3.58.
Found: C, 58.21; H, 7.26; N, 3.53.
J¼8.9 Hz, 1H), 8.27 (dd, J¼2.5, 8.9 Hz, 1H), 8.45 (d, J¼2.5 Hz, 1H)
ppm; 13C NMR (CDCl3, 50 MHz):
d 14.1 (q), 22.7 (t), 28.0 (t), 28.8 (t),
29.1 (t), 29.3 (t), 29.4 (t), 29.5 (t), 29.6 (t, 2C), 31.9 (t), 32.6 (t), 122.6
(d, J¼274.5 Hz), 122.3 (q, J¼6.0 Hz), 126.2 (d), 126.8 (d), 128.0 (d,
J¼32.4 Hz), 144.0 (s), 148.0 (s) ppm; ESIMS (m/z): 392.1891 [Mþ1]þ.
Anal. Calcd for C19H28F3NO2S: C, 58.29; H, 7.21; N, 3.58. Found: C,
58.23; H, 7.28; N, 3.51.
4.3.13. 5-Methyl-2-nitrophenyl phenyl sulfide (7ea). Yellow solid; Rf
(100% pet. ether) 0.3; mp: 89e90 ꢀC; IR (CHCl3)
n
: 1577, 1460, 1377,
1217, 1158, 1018, 824, 722 cmꢂ1
;
1H NMR (CDCl3, 200 MHz):
d
2.19
4.3.19. 3-Nitro-4-(pyridin-2-ylthio)benzonitrile (7hb). Yellow solid;
(s, 3H), 6.59 (d, J¼1.6 Hz, 1H), 6.98 (dd, J¼1.5, 8.5 Hz, 1H), 7.44e7.60
Rf (15% EtOAc/pet. ether) 0.2; mp: 131e132 ꢀC; IR (CHCl3)
n
: 2233,
1716, 1573, 1512, 1458, 1377, 1291, 1155, 1051, 904, 767 cmꢂ1 1H
NMR (CDCl3, 200 MHz):
(m, 5H), 8.12 (d, J¼8.4 Hz, 1H) ppm; 13C NMR (CDCl3, 50 MHz):
;
d
21.6 (q), 125.8 (d), 125.9 (d), 128.3 (d), 129.9 (d), 130.0 (d, 2C), 131.0
d
7.30 (d, J¼8.6 Hz, 1H), 7.42 (ddd, J¼1.2,
(s), 135.8 (d, 2C), 139.4 (s), 142.1 (s), 144.8 (s) ppm; ESIMS (m/z):
268.0926 [MþNa]þ. Anal. Calcd for C13H11NO2S: C, 63.65; H, 4.52; N,
5.71. Found: C, 63.57; H, 4.49; N, 5.67.
4.8, 7.5 Hz, 1H), 7.60e7.70 (m, 2H), 7.85 (dt, J¼1.9, 7.7 Hz, 1H), 8.49
(d, J¼1.8 Hz, 1H), 8.68e8.72 (m, 1H) ppm; 13C NMR (CDCl3,
50 MHz):
d 109.7 (s), 116.5(s), 124.2 (d), 129.3 (d), 129.4 (d), 130.8
(d), 135.1 (d), 138.3 (d), 142.1 (s), 145.8 (s), 151.5 (d), 153.0 (s) ppm;
ESIMS (m/z): 330.2256 [Mþ1]þ. Anal. Calcd for C12H7N3O2S: C,
56.02; H, 2.74; N, 16.33. Found: C, 55.91; H, 2.79; N, 16.21.
4.3.14. 5-Methyl-2-nitrophenyl 2-pyridinyl sulfide (7eb). Brown
solid; Rf (15% EtOAc/pet. ether) 0.2; mp: 62e63 ꢀC; IR (CHCl3)
n:
;
1574, 1520, 1451, 1338, 1216, 1116, 769 cmꢂ1 1H NMR (CDCl3,
200 MHz): 2.30 (s, 3H), 7.11e7.16 (m, 1H), 7.24e7.31 (m, 1H), 7.52
d
4.3.20. 4-(n-Dodecylthio)-3-nitrobenzonitrile (7hd). Yellow solid; Rf
(dt, J¼1.0, 7.8 Hz, 1H), 7.61e7.64 (m, 1H), 7.72 (dt, J¼1.9, 7.7 Hz, 1H),
(5% EtOAc/pet. ether) 0.2; mp: 108e109 ꢀC; IR (CHCl3)
n
: 2234,1715,
8.06 (d, J¼8.4 Hz, 1H), 8.59e8.63 (m, 1H) ppm; 13C NMR (CDCl3,
1520, 1463, 1377, 1346, 1269, 1112, 721 cmꢂ1
200 MHz):
;
1H NMR (CDCl3,
50 MHz):
d
21.9 (q), 121.1 (d), 122.7 (d), 125.6 (d), 127.6 (d), 127.8 (d),
d
0.86 (t, J¼6.5 Hz, 3H), 1.25 (br s, 16H), 1.40e1.52 (m,
137.6 (d), 144.5 (s), 145.6 (s), 150.7 (d), 155.8 (s), 158.9 (s) ppm;
ESIMS (m/z): 269.0455 [MþNa]þ. Anal. Calcd for C12H10N2O2S: C,
58.52; H, 4.09; N, 11.37. Found: C, 58.46; H, 4.17; N, 11.24.
2H), 1.68e1.80 (m, 2H), 2.98 (t, J¼7.4 Hz, 2H), 7.49 (d, J¼8.6 Hz, 1H),
7.75 (dd, J¼1.9, 8.5 Hz, 1H), 8.51 (d, J¼1.9 Hz, 1H) ppm; 13C NMR
(CDCl3, 50 MHz): d 14.1 (q), 22.7 (t), 27.4 (t), 29.0 (t), 29.1 (t), 29.3 (t),
29.4 (t), 29.5 (t), 29.6 (t, 2C), 31.9 (t), 32.4 (t),107.7 (s), 116.8 (s),127.1
(d), 129.9 (d), 135.2 (d), 145.5 (s) ppm; ESIMS (m/z): 349.07 [Mþ1]þ.
Anal. Calcd for C19H28N2O2S: C, 65.48; H, 8.10; N, 8.04. Found: C,
65.51; H, 8.01; N, 7.93.
4.3.15. 2-(5-Methyl-2-nitrophenylthio)benzo[d]thiazole
(7ec). Yellow solid; Rf (100% pet. ether) 0.3; mp: 118e119 ꢀC; IR
(CHCl3)
NMR (CDCl3, 200 MHz):
(m, 2H), 7.85e7.90 (m, 1H), 8.07e8.15 (m, 2H) ppm; 13C NMR
(CDCl3, 50 MHz): 21.7 (q), 121.5 (d), 123.6 (d), 125.8 (d), 126.1 (d),
n ;
: 1712, 1582, 1464, 1377, 1166, 1075, 975, 723 cmꢂ1 1H
d
2.30 (s, 3H), 7.15e7.21 (m, 2H), 7.42e7.59
4.3.21. 2-[(4-Nitrobenzyl)sulfanyl]pyridine (7ib)22d. Yellow solid; Rf
(15% EtOAc/pet. ether) 0.3; mp: 63e64 ꢀC; 1H NMR (CDCl3,
d
126.7 (d), 128.4 (d), 130.8 (d), 132.9 (s), 137.5 (s), 144.5 (s), 145.5 (s),
153.6 (s), 161.2 (s) ppm; ESIMS (m/z): 324.99 [MþNa]þ. Anal. Calcd
for C14H10N2O2S2: C, 55.61; H, 3.33; N, 9.26. Found: C, 55.53; H,
3.26; N, 9.19.
200 MHz):
d
4.49 (s, 2H), 7.0 (ddd, J¼1.1, 5.0, 7.3 Hz, 1H), 7.15 (dt,
J¼1.0, 8.1 Hz, 1H), 7.47 (ddd, J¼1.9, 7.4, 9.3 Hz, 1H), 7.52e7.59 (m,
2H), 8.08e8.15 (m, 2H), 8.41e8.45 (m, 1H) ppm; 13C NMR (CDCl3,
50 MHz):
d 33.2 (t), 120.0 (d), 122.3 (d), 123.6 (d, 2C), 129.8 (d, 2C),
136.1 (d), 146.6 (s), 146.9 (s), 149.4 (d), 157.1 (s) ppm; ESIMS (m/z):
247.3450 [Mþ1]þ. Anal. Calcd for C12H10N2O2S: C, 58.52; H, 4.09; N,
11.37. Found: C, 58.43; H, 4.13; N, 11.29.
4.3.16. 1-Dodecylthio-5-methyl-2-nitrobenzene (7ed). Yellow solid;
Rf (100% pet. ether) 0.2; mp: 51e52 ꢀC; IR (CHCl3)
n
: 1596, 1513,
1459, 1377, 1335, 1219, 1114, 823, 721 cmꢂ1
200 MHz):
;
1H NMR (CDCl3,
d
0.87 (t, J¼6.5 Hz, 3H), 1.25 (br s, 16H), 1.42e1.52 (m,
4.3.22. n-Dodecyl p-nitrobenzyl sulfide (7id)22h. White solid; Rf
2H), 1.66e1.77 (m, 2H), 2.42 (s, 3H), 2.93 (d, J¼7.3 Hz, 2H), 7.0 (dd,
(100% pet. ether) 0.2; mp: 38e39ꢀC(lit. 31e33 ꢀC); IR (CHCl3)
n
: 1606,
1H NMR (CDCl3,
0.86 (t, J¼6.5 Hz, 3H),1.23 (br s,18H),1.40e1.53 (m, 2H),
2.35e2.45 (m, 2H), 3.75 (s, 2H), 7.43e7.50 (m, 2H), 8.13e8.20 (m,
2H) ppm; 13C NMR (CDCl3, 50 MHz):
14.1 (q), 22.6 (t), 28.8 (t), 29.7
J¼1.6, 8.5 Hz, 1H), 7.14 (br s, 1H), 8.11 (d, J¼8.5 Hz, 1H) ppm; 13C
1526, 1459, 1376, 1346, 1109, 858, 721 cmꢂ1
200 MHz):
;
NMR (CDCl3, 50 MHz):
d
14.1 (q), 21.7 (q), 22.7 (t), 27.8 (t), 29.1 (t),
d
29.2 (t), 29.3 (t), 29.44 (t), 29.5 (t), 29.6 (t, 2C), 31.9 (t), 32.3 (t),125.2
(d), 126.2 (d), 126.6 (d), 138.5 (s), 143.9 (s), 144.6 (s) ppm; ESIMS (m/
z): 360.14 [MþNa]þ. Anal. Calcd for C19H31NO2S: C, 67.61; H, 9.26; N,
4.15. Found: C, 67.53; H, 9.31; N, 4.06.
d
(t), 29.2 (t), 29.4 (t), 29.5 (t), 29.6 (t, 2C), 31.6 (t), 31.9 (t), 35.8 (d),
123.7 (d, 2C),129.6(d, 2C),146.6 (s) ppm. Anal. Calcd for C19H31NO2S:
C, 67.61; H, 9.26; N, 4.15. Found: C, 67.53; H, 9.31; N, 4.06.
4.3.17. 1-Dodecylthio-4-iodo-2-nitrobenzene (7fd). Yellow solid; Rf
(100% pet. ether) 0.3; mp: 60e61 ꢀC; IR (CHCl3)
n
: 1580, 1538, 1463,
4.3.23. 2-(2-Pyridyl)quinoline (7jb)22f. Colorless oil; Rf (10% EtOAc/
1377, 1333, 1249, 1168, 1054, 812, 718 cmꢂ1
;
1H NMR (CDCl3,
pet. ether) 0.2; IR (CHCl3)
n
: 1615,1588,1572,1556, 1448,1418,1295,
200 MHz):
d
0.87 (t, J¼6.5 Hz, 3H), 1.24 (br s, 16H), 1.39e1.49 (m,
1120, 1095, 941, 818, 760 cmꢂ1
;
1H NMR (CDCl3, 200 MHz):
d
7.18
2H), 1.64e1.75 (m, 2H), 2.91 (t, J¼7.4 Hz, 2H), 7.11 (d, J¼8.6 Hz, 1H),
(ddd, J¼2.0, 4.9, 6.8 Hz, 1H), 7.40 (d, J¼8.6 Hz, 1H), 7.48 (ddd, J¼1.2,
7.78 (dd, J¼2.0, 8.6 Hz, 1H), 8.48 (d, J¼2.0 Hz, 1H) ppm; 13C NMR
7.0, 8.1 Hz, 1H), 7.57e7.71 (m, 3H), 7.74 (d, J¼1.3, 8.0 Hz, 1H),

7650
Y. Goriya, C.V. Ramana / Tetrahedron 66 (2010) 7642e7650
7.96e8.02 (m, 2H), 8.53e8.57 (m, 1H) ppm; 13C NMR (CDCl3,
50 MHz): 122.0 (d), 122.7 (d), 126.4 (d), 126.5 (d), 126.7 (d), 127.5
(d), 128.7 (d), 129.9 (d), 136.6 (d), 137.0 (d), 148.3 (s), 150.2 (d), 156.3
(s), 157.6 (s) ppm; MALDIeMS (m/z): 239.0616 [Mþ1]þ. Anal. Calcd
for C14H10N2S: C, 70.56; H, 4.23; N, 11.76. Found: C, 70.61; H, 4.16; N,
11.68.
Lang, F. R.; Zewge, D.; Houpis, I. N.; Volante, R. P. Tetrahedron Lett. 2001, 42,
3251e3254.
8. Selected reviews on thioether synthesis: (a) Ley, S. V.; Thomas, A. W. Angew.
Chem., Int. Ed. 2003, 42, 5400e5449; (b) Kondo, T.; Mitsudo, T.-A. Chem. Rev.
2000, 100, 3205e3220.
d
9. For reduction of azides see: (a) Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V.
Angew. Chem., Int. Ed. 2005, 44, 5188e5240; (b) Scriven, E. F. V.; Turnbull, K.
Chem. Rev. 1988, 88, 297e368; (c) Zhao, H.; Fu, H.; Qiao, R. J. Org. Chem. 2010, 75,
3311e3316; (d) Schneggenburger, P. E.; Worbs, B.; Diederichsen, U. J. Pept. Sci.
2010, 16, 10e14; (e) Bures, J.; Martın, M.; Urpı, F.; lVilarrasa, J. J. Org. Chem. 2009,
74, 2203e2206; (f) Ayesa, S.; Samuelsson, B.; Classon, B. Synlett 2008, 97e99;
(g) Postigo, A.; Kopsov, S.; Ferreri, C.; Chatgilialoglu, C. Org. Lett. 2007, 9,
5159e5162; (h) Benati, L.; Bencivenni, G.; Leardini, R.; Nanni, D.; Minozzi, M.;
Spagnolo, P.; Scialpi, R.; Zanardi, G. Org. Lett. 2006, 8, 2499e2502.
10. Selected papers on the coupling of aryl halides with sodium azide see: (a)
D’Anna, F.; Marullo, S.; Noto, R. J. Org. Chem. 2010, 75, 767e771; (b) D’Anna, F.;
Marullo, S.; Noto, R. J. Org. Chem. 2008, 73, 6224e6228; (c) Tao, C. Z.; Cui, X.; Li,
J.; Liu, A. X.; Liu, L.; Guo, Q. X. Tetrahedron Lett. 2007, 48, 3525e3529; (d) An-
dersen, J.; Bolvig, S.; Liang, X. F. Synlett 2005, 2941e2947; (e) Andersen, J.;
4.3.24. 2-[n-Dodecylmercapto]-quinoline (7jd)22g. Colorless oil; Rf
(100% pet. ether) 0.3; IR (CHCl3)
n
: 1614, 1594, 1497, 1465, 1376,
;
1294, 1137, 1088, 814, 779, 747 cmꢂ1
1H NMR (CDCl3, 200 MHz):
d
0.88 (t, J¼6.5 Hz, 3H), 1.25 (br s, 16H), 1.41e1.51 (m, 2H), 1.70e1.81
(m, 2H), 3.33 (t, J¼7.3 Hz, 2H), 7.18 (d, J¼8.7 Hz, 1H), 7.38 (ddd,
J¼1.2, 7.1, 8.1 Hz, 1H), 7.57e7.69 (m, 2H), 7.82 (d, J¼8.7 Hz, 1H),
7.90e7.94 (m, 1H) ppm; 13C NMR (CDCl3, 50 MHz):
d 14.1 (q), 22.6
(t), 29.0 (t), 29.2 (t), 29.3 (t, 2C), 29.5 (t), 29.6 (t, 2C), 29.6 (t), 29.7 (t),
31.9 (t), 121.0 (d), 125.0 (d), 125.8 (s), 127.5 (d), 128.0 (d), 129.4 (d),
135.0 (d), 148.3 (s), 159.6 (s) ppm; MALDIeMS (m/z): 330.2256
[Mþ1]þ. Anal. Calcd for C21H31NS: C, 76.54; H, 9.48; N, 4.25. Found:
C, 76.61; H, 9.43; N, 4.17.
€
Madsen, U.; Bjorkling, F.; Liang, X. Synlett 2005, 2209e2213; (f) Feldman, A. K.;
Colasson, B.; Fokin, V. V. Org. Lett. 2004, 6, 3897e3899; (g) Zhu, W.; Ma, D. W.
Chem. Commun. 2004, 888e889.
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Biomol. Chem. 2007, 5, 1695e1701.
12. During this work in progress, Molander and co-workers reported the formation
of aniline derivatives during the azidation of aryl tetrafluorborates and is
substrate specificdsee: Cho, Y. A.; Kim, D. S.; Ahn, H. R.; Canturk, B.; Molander,
G. A.; Ham, J. Org. Lett. 2009, 11, 4330e4333.
13. During this manuscript in preparation, Qiao and Sajiki groups reported a simi-
lar copper catalyzed direction amination of aryl halide using azide as the am-
monia source. (a) Monguchi, Y.; Maejima, T.; Mori, S.; Maegawa, T.; Sajiki, H.
Chem.dEur. J. 2010, 16, 7372e7375; (b) Ref. 9c.
14. (a) Lee, G.-Y. J. Korean Chem. Soc. 2009, 53, 257e265; (b) Bartoli, G.; Di Antonio,
G.; Giovannini, R.; Giuli, S.; Lanari, S.; Paoletti, M.; Marcantoni, E. J. Org. Chem.
2008, 73, 1919e1924; (c) Antsyshkina, A. S.; Sadikov, G. G.; Sergienko, V. S.;
Poznyak, A. L. Crystallogr. Rep. 2004, 49, 783e787.
4.3.25. 4-Methoxyphenyl phenyl sulfide (7ka). Colorless oil; Rf
(100% pet. ether) 0.3; 1H NMR (CDCl3, 200 MHz):
d
3.82 (s, 3H),
6.86e6.93 (m, 2H), 7.09e7.28 (m, 5H), 7.38e7.46 (m, 2H) ppm; 13C
NMR (CDCl3, 50 MHz): 55.3 (q), 115.0 (d, 2C), 124.2 (s), 125.7 (d),
d
128.2 (d, 2C), 128.9 (d, 2C), 135.4 (d, 2C), 138.6 (s), 159.8 (s) ppm.
Acknowledgements
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We thank the Ministry of Science and Technology for funding
through the Department of Science and Technology under the
Green Chemistry Program (NO. SR/S5/GC-20/2007).
Supplementary data
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Supporting information available: NMR spectra of representa-
tive compounds. Supplementary data associated with this article
can be found in online version at doi:10.1016/j.tet.2010.07.032.
These data include MOL files and InChIKeys of the most important
compounds described in this article.
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