Dual catalysis by Cu(i): Facile single step click and intramolecular C-O bond formation leading to triazole tethered dihydrobenzodioxines/benzoxazines/ benzoxathiines/benzodioxepines

Article abstract of DOI:10.1039/c3ob41332b

Dual copper catalysis, involving two different reactions, click (alkyne-azide) and carbon-oxygen bond formation (aryl iodide-secondary alcohol) in a single step, is reported. Synthesis of novel benzodioxines (benzodioxanes), benzoxazines, benzoxathiines and benzodioxepines, which feature benzo-condensed six or seven membered rings containing two hetero-atoms attached to a 1,2,3-triazole, is described. As an extension, such compounds were also synthesised by ring opening of epoxide and cyclisation using Cu(i). All the key products have been characterized by single crystal X-ray crystallography.

Full text of DOI:10.1039/c3ob41332b

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N
O
X
N
N
X = O, N-Ts, S
N3
HO
R'
CuI/ Picolinic acid/
Cs2CO3
I
R
N
N
R
+
N
Toluene, 120 oC/12 h
X
R'
X = O, N-Ts, S, CH2O
O
R
O
X = CH2O
N3
HO
CuI/ Picolinic acid/
Cs2CO3
N
N
I
O
O
N
R
+
O
Toluene, 120 oC/12 h
H
H
R

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DOI: 10.1039/C3OB41332B
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ARTICLE TYPE
Dual catalysis by Cu(I): Facile single step click and intramolecular C-O
bond formation leading to triazole tethered dihydrobenzodioxines/
benzoxazines/ benzoxathiines/ benzodioxepines
M. Nagarjuna Reddya and K. C. Kumara Swamy*a
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Dual copper catalysis, involving two different reactions, click (alkyne-azide) and carbon-oxygen bond
formation (aryl iodide-secondary alcohol) in a single step, is reported. Synthesis of novel benzodioxines
(benzodioxanes), benzoxazines, benzoxathiines and which feature benzo-condensed six or seven
10 membered rings containing two hetero-atoms attached to a 1,2,3-triazole, is described. As an extension,
such compounds were also synthesised by the ring opening of epoxide and cyclisation using Cu(I). All the
key products have been characterized by single crystal X-ray crystallography.
sequential, copper-catalyzed click reaction and intramolecular
direct arylation of triazoles thus formed.10 In continuation of this
work, we intended to construct benzo-dioxine, -oxazine,-
oxathiine and -dioxepine heterocyclic ring utilizing atom
50 economical copper-catalysed click reaction and C-O bond
formation in one-pot. The results in which Cu(I) species plays the
role of a ‘dual catalyst’ are reported herein.
Introduction
Among the copper catalysed reactions, the most promising atom
15 economy reaction in the current scenario is the click reaction
between alkynes and organic azides leading to triazoles because
of the potential use of the products, ranging from medicinal
chemistry to materials science.1-2 In the last few years, copper
catalysts are also extensively utilized in the construction of C-X
20 (X = N, S, O, P) bond3 with aryl halides as coupling partners.
Hartwig and Buchwald reported the palladium catalyzed
Results and Discussion
Generation of the required starting materials 2a-l was
reactions with alcohols and aryl halide.4 The main drawback in 55 accomplished as shown in Scheme 1; details of experimental data
the palladium catalyzed reactions is the limited number of ligands
and possibility of β-hydrogen elimination in secondary alcohols.
25 As a result, copper catalysis is utilized in constructing carbon-
oxygen5 bond with secondary alcohol and arylhalides.6 Research
is focusing towards one-pot reactions to reduce wastage of
chemicals, time and for its economical value.7 Literature survey
revealed that such one pot synthesis of dihydro-benzodioxine,
30 benzoxazine and benzoxathiine having 1,2,3-triazole analogues is
not reported till date. Benzo-condensed six membered
heterocyclic compounds containing two heteroatoms have wide
applications in medicinal chemistry.8 Among these, benzo-
dioxine (e.g., domoxin, piperoxan, eltoprazine, fluparoxan,
35 idazoxan, prosympal) and benzoxathiine core structure are found
in a variety of pharmaceutically useful (e.g., α-adrenergic
blockers,8g estrogenic agent8h) compounds. We believe that
derivatisation on these heterocycles will have substantial benefits
in medicinal chemistry and hence are interested in constructing
40 both these apparently-simple looking heterocyclic rings, with a
variety of substituents.
for these substrates are given in the supplementary material.
As a part of our ongoing research into the transition-metal-
catalyzed C-C, C-N and C-O bond forming reactions,9 we
planned to synthesise heterocyclic moieties tethered with triazole
45 moiety. Recently, we showed a simple method for the one pot
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DOI: 10.1039/C3OB41332B
a
Table 1: Optimization of the reaction conditions for the synthesis of 3
N3
O
O
Cl
(2 equiv)
R
HO
I
R
R
I
I
Entr
y
CuX
Ligand
Base
Solvent
Yield
(%)b
55c
(ii)
(i)
XH
X
1a-1h
X
2a-2h
1
CuI
-----
Cs2CO3
Toluene
X = O, N-Ts, S
2
3
4
CuI
CuI
CuI
DMEDA
L-Proline
Cs2CO3
Cs2CO3
Cs2CO3
Toluene
Toluene
Toluene
62
49
55
X = O, R = H
X = O, R = 4-tBu
X = O, R = 4-Cl
X = O, R = 4,6-diMe (1d)
X = O, R = 3,4-(-C4H4-)(1e)
(1a)
(1b)
(1c)
X = O, R = H
(2a)
(2b)
(2c)
(2d)
X = O, R = 4-tBu
X = O, R = 4-Cl
X = O, R = 4,6-diMe
8-Hydroxy-
quinoline
X = O, R = 3,4-(-C4H4-) (2e)
5
6
CuI
Bipyridine
Cs2CO3
Toluene
75
X = NTs, R = H
X = NTs, R = 4-Me
X = S, R = H
(1f)
(1g)
(1h)
X = NTs, R = H
X = NTs, R = 4-Me
X = S, R = H
(2f)
(2g)
(2h)
CuI
Picolinic
acid
Cs2CO3
Toluene
89
Conditions: (i) K2CO3 (1.5 equiv), CH3CN, reflux, 12 h
(ii) NH4Cl (2.0 equiv), NaN3 (4.0 equiv), MeOH, 50 oC, 10 h
7
8
9
CuBr
Picolinic acid
Cs2CO3
Toluene
71
CuCl
Cu2O
Picolinic acid
Picolinic acid
Cs2CO3
Cs2CO3
Toluene
Toluene
66
48
N3
N3
N3
HO
N
N3
HO
O
I
HO
10
11
12
13
14
CuI
CuI
CuI
CuI
CuI
Picolinic acid
Picolinic acid
Picolinic acid
Picolinic acid
Picolinic acid
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Toluene
Water
51
25c
37c
41d
55
HO
I
I
Br
X
S
O
O
PEG-400
Et2CO3
DMF
O
2j
2l
2k
2i
Scheme 1
aQuantities used: 2a (0.5 mmol), phenylacetylene (0.55 mmol), CuX (10
mol%), ligand (20 mol%), base (3.0 equiv), Toluene (1 mL) at 120 oC (oil
30 bath temperature). bisolated yields. ctriazole 4 was remained (entry 1 -
30%; entry 11 - 50%; entry 12 - 37%). dene-triazole 5 formed in 35%.
Initial experiments were performed on 1-azido-3-(2-
iodophenoxy)propan-2-ol 2a and phenylacetylene in the presence
of copper(I) iodide (10 mol %) and caesium carbonate (3 equiv)
in toluene at 120 oC/ 12 h to effect click reaction and
intramolecular C-O bond formation. This procedure afforded the
triazole linked dihydrobenzodioxine 3 in 55% yield (Scheme 2).
5
Ph
N
N
N
N
N
Ph
N
HO
I
I
O
O
N3
HO
4
5
I
O
O
N
Conditions
N
N
Ph
+
With the optimized conditions (entry 6, Table 1) in hand, we
conducted the reactions of various terminal acetylenes with 2a for
35 the synthesis of triazole based benzodioxine derivatives (Scheme
3). Both electron releasing and withdrawing groups on acetylene
afforded triazole benzodioxane (6-14) in good yields, the method
worked well for naphthyl, vinyl and aliphatic alkynes also.
Activated alkynes also afforded good yield when reacted with
40 substrate 2a. To further explore the efficacy and generality of the
method, reactions using different substituted 1-azido-3-(2-
iodobenzyloxy)-propan-2-ol (2b-e) were investigated for this
one-pot reaction to synthesise products 15-18 in good yields.
Though two different kinds of reaction were performed in a
45 single step, the yields (isolated) obtained were good in most
cases. All the compounds were characterised by IR, NMR and
HRMS and the structure of compound 16 was confirmed by X-
ray crystallography (Figure 1).
O
2a
3
Ph
Conditions: CuI (10 mol %)/ Cs2CO3 (3.0 equiv)/ Toluene/ 120 oC/ 12 h
Scheme 2
10
Our next step was directed toward searching the best condition
to maximize the yield of compound 3 by screening various
reaction parameters as depicted in Table 1. Among the ligands
15 employed for screening, bipyridine and picolinic acid proved to
be promising in obtaining the compound 3 in good yield (Table 1,
entries 5, 6), however, we selected to use picolinic acid as it is
economically attractive and biocompatible. Other ligands
employed were ineffective in increasing the yield. Then the effect
20 of copper salts and base were examined (entries 7-10), they
afforded lower yields. As a solvent, toluene was the best when
compared to DMF, PEG-400 or water. In the case of diethyl
carbonate as solvent, elimination product 5 was isolated along
with 1,3-dipolar cyclised product
25 benzodioxine was not observed.
4
and the expected
2
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N3
20 20 was further confirmed by X-ray crystallography (Figure 2).
HO
N
R'
R'
Conditions
O
O
I
N
N
N3
R
+
R'
Conditions
O
HO
N
R'
(a)
I
O
N
N
R
+
R
R''
R''
N
N
O
O
N
N
O
R
N
N
Ts
R' = H (2f), Me (2g)
N
R
Ts
N
R' = H, R = Ph
19 (86%)
= cyclohexenyl 20 (77%, X-ray)
O
= C8H17
R' = Me, R = Ph
21 (76%)
22 (82%)
10 (84%)
R = Ph
3 (89%)
= 4-MeO-C6H4 6 (85%)
= 4-Me-C6H4 7 (87%)
= 4-O2N-C6H4 8 (82%)
= 2-OHC-C6H4 9 (80%)
= cyclohexenyl 23 (78%)
= C8H17 24 (74%)
N3
HO
I
O
N
Conditions
N
N
(b)
+
R
N
O
O
N
N
I
N
S
S
N
N
R = Ph
= cyclohexenyl 26 (80%)
= C8H17 27 (77%)
25 (84%)
2h
R
O
O
12 (79%)
O
11 (75%)
O
Ph
Conditions: CuI (10 mol %)/ Picolinic acid (20 mol %)/ Cs2CO3 (3.0 equiv)/
Toluene/ 120 oC/ 12 h
Scheme 4
N
O
O
N
N
N
N
N
O
O
C8H17
13 (78%)
14 (72%)
R'
N
O
N
O
N
N
N
N
O
O
Ph
Ph
R' = Cl 16 (82%, X-ray)
= t-Bu 17 (86%)
15 (81%)
N
N
O
N
O
Ph
18 (78%)
Conditions: CuI (10 mol %)/ Picolinic acid (20 mol %)/ Cs2CO3 (3.0 equiv)/
Toluene/ 120 oC/ 12 h
Scheme 3
Figure 2. ORTEP diagram of compound 20. Selected bond lengths [Å]
with esd’s in parentheses: C1-O1 1.366 (4) C8-O1 1.423 (3) N2-N3
25 1.335(4) N3-N4 1.303(4).
Till this point, we were successful in synthesising
benzodioxines, benzoxazines and benzoxathiine derivatives. To
expand this methodology, we made an effort to synthesise seven
membered ring containing compounds also. To achieve this,
30 substrate 2i was prepared in two steps from 2-iodobenzyl alcohol
and epichlorohydrin. Following the optimized condition, we
conducted reaction between 2i and terminal acetylenes which
afforded triazole based benzodioxepine derivatives 28-31 in good
yields. In this case also, gratifyingly, we were able to construct
35 three new bonds in a single step involving click reaction and
intramolecular C-O bond between secondary alcohol and aryl
iodide. The structure of compound 30 was confirmed by X-ray
crystallography (Figure 3).
Figure 1. ORTEP diagram of compound 16. Selected bond lengths [Å]
with esd’s in parentheses: C6-O2 1.376 (4) C8-O2 1.438 (4) N1-N2
1.338(4) N3-N2 1.314(4).
5
After synthesizing various substituted triazole based
benzodioxine derivatives successfully, we planned to extend this
methodology to benzoxazines and benzoxathiine based triazoles,
10 as these moieties also have the same importance as that of
benzodioxine derivatives. To achieve this, we prepared substrates
2f, 2g and 2h from 2-iodoaniline and 2-iodothiophenol
respectively as shown in Scheme 1 above. These substrates were
reacted with phenyl, vinyl and aliphatic alkynes under the
15 optimized conditions to furnish the expected triazole based
benzoxazines (19-24) and benzoxathiines (25-27) in good yields
(Scheme 4). Precursors 2f and 2g showed multiple peaks in NMR
data due to the possibility of rotamers,11 after cyclisation, the
observed NMR data was as expected. The structure of compound
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N
N
N3
N
HO
O
O
I
R
Conditions
R
+
O
R = Ph
= 4-OMe-Ph
= 4-NO2-Ph
28 (77%)
29 (83%)
30 (72%, X-ray)
2i
= cyclohexene 31 (69%)
Conditions: CuI (10 mol %)/ Picolinic acid (20 mol %)/ Cs2CO3 (3.0 equiv)/
Toluene/ 120 oC/ 12 h
Scheme 5
Figure 4. ORTEP diagram of compound 32. Selected bond lengths [Å]
25 with esd’s in parentheses: C6-O3 1.353 (2) C7-C8 1.320 (2) N1-N3
1.313(2) N3-N2 1.326(2).
Thus copper catalyzed one-pot click reaction and
intramolecular C-O bond formation was successfully employed
30 on aryl halide precursors. We then wondered whether our
methodology is applicable to make a carbon-oxygen bond
between vinyl iodide and alcohol or not. To achieve this,
substrate 2k was prepared from 2-iodo-cyclohexenol and 3-
chloro-2-epoxy propane (Scheme 1). Later, substrate 2k was
35 subjected to optimized condition with terminal acetylenes to
obtain 1,4-dioxine ring products. Substrate 2k has two chiral
centres, which shows a possibility of four stereoisomers. The
Figure 3. ORTEP diagram of compound 30. Selected bond lengths [Å]
with esd’s in parentheses: C1-O1 1.381 (3) C9-O1 1.442 (2) N1-N2
1.341(3) N3-N2 1.310(3).
5
In a manner similar to above, we attempted to synthesise seven
membered sultam moieties from 2j. Precursor 2j was synthesised
from 4-methyl-2-iodo-sulfonamide and epichlorohydrin. Later,
1
presence of two sets of equal intensity peaks in the H and 13C
NMR of these compounds suggests the presence of diastereomers
40 in 1:1 ratio. Satisfyingly, though, the reaction does work
efficiently in this case also.
10 we performed reaction between 2j and phenylacetylene in an
effort to obtain seven membered sultam derivatives. To our
surprise, this reaction led to the ring opened product 32 as shown
in Scheme 6. This product arises due to the abstraction of proton
from CH2 moiety adjacent to N and subsequent migration giving
15 the phenolic derivative 32. In our previous paper, under base
mediated condition, we reported this kind of elimination and
another group also reported this kind of phenol derivative from
thiaflavans recently.10,12 The structure of compound 32 was
confirmed by X-ray crystallography (Figure 4).
N3
I
HO
N
O
O
Conditions
N
N
+
R
H
O
H
H
R
2k
R = Ph,
33 (75%)
4-Me-Ph, 34 (71%)
4-NO2-Ph, 35 (69%)
Conditions: CuI (10 mol %)/ Picolinic acid (20 mol %)/ Cs2CO3 (3.0 equiv)/
Toluene/ 120 oC/ 12 h
20
N
N
Scheme 7
N3
N
HO
N
In general, it is expected that the aryl bromides are less reactive
45 than aryl iodides in reactions such as those described above. In
line with this, the reaction between bromo precursor 2l and
phenylacetylene utilizing the optimized condition described
above afforded the expected benzodioxine 3 along with the
uncyclised product 36 (Scheme 8). Thus, under these conditions,
50 coupling of aryl/vinyl iodides are more successful than of aryl
bromides towards a secondary alcohol.
O
S
I
Ph
Conditions
Ph
+
N
S
O
O
O
O
2j
N
N
N
OH
Ph
N
S
O
O
32 (65%, X-ray)
Conditions: CuI (10 mol %)/ Picolinic acid (20 mol %)/ Cs2CO3 (3.0 equiv)/
Toluene/ 120 oC/ 12 h
Scheme 6
4
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N3
methodology copper/ligand/base are required.
Br
HO
Conditions
+
Ph
N
N
N
O
Ph
2l
N
HO
I
N
N
O
O
N
N
N
conditions
Toluene
120 oC/ 12 h
N
N
Ph
N
Ph
Br
O
O
HO
4
3
+
Ph
O
conditions
(a) CuI (10 mol %)/picolinic acid (20 mol %) noreaction
O
3 (23%)
36 (56%)
(b) Cs2CO3 (3.0 equiv)
noreaction
62%
(c) CuI (10 mol %)/Cs2CO3 (3.0 equiv)
Conditions: CuI (10 mol %)/ Picolinic acid (20 mol %)/ Cs2CO3
(3.0 equiv)/Toluene/ 120 oC/ 24 h
Scheme 10
Scheme 8
There are two plausible pathways15-16 to explain the etherification
step: (i) involves the oxidative addition of copper(I) source across
35 C-X bond generating Cu(III) intermediate A, followed by
replacement of X with the nucleophile in the presence of base
forming complex B, or (ii) nucleophile reacts with Cu(I) source
to form complex C16 and further oxidative addition onto C-X
bond leading to complex B. In both these pathways, reductive
40 elimination16c is the final step affording the desired product 3.
Cs2CO3 acts as a base and picolinic acid (or picolinate) acts as the
ligand (L). Recent reports favour the second mechanism.16
After utilising [Cu]-catalysis successfully in two mechanistically
different
reactions
to
construct
triazole
appended
benzodioxines/benzoxazines, we envisioned to synthesise such
derivatives starting from the epoxide 1. There are only a handful
of reports available related to ring opening of epoxides/aziridines
and further cyclisation by copper-catalysis to obtain the
benzodioxines/benzoxazine/benzothiines.6 Thus, in a one-pot
procedure starting from the epoxides (1a, 1b, 1d, 1f) the triazole
10 fused benzodioxines (37-39) and benzoxazine (40) were obtained
in good yield. This reaction involves the ring opening of epoxide
by benzotriazole and intramolecular cyclisation forming a new C-
O bond (Scheme 9). The intermediate 41 could be readily isolated
by the reaction of benzotriazole with the epoxide 1a under neat
15 conditions at 100 oC.
5
Ln
Ln
Cu
Ln
Cu
Cu
I
I
I
O
X
OH
T
O
T
T
X
O
N
R'
R'
O
X
I
O
O
N
O
N
N
Conditions
N
+
A
B
C
N
H
X
T = triazole; L = picolinic acid (picolinate)
R''
1a, 1b, 1d, 1f
R''
X = O, R' = R'' = H
X = O, R' = tBu, R'' = H 38 (77%)
X = O, R' = R'' = Me 39 (73%)
X = N-Ts, R' = R'' = H 40 (81%)
37 (74%)
Chart 1
Conditions: (i) 100 oC, 1h then CuI (10 mol %)/ Picolinic acid (20 mol %)/
Cs2CO3 (3.0 equiv)/Toluene/ 120 oC/ 12 h
45 Conclusion
We have successfully demonstrated a simple one-pot synthesis of
1,2,3-triazole appended benzodioxines (benzodioxanes),
HO
I
N
N
N
benzoxazines and benzoxathiine. The involvement of two
different kinds of reaction, a click and an intramolecular
50 carbon-oxygen bond formation using Cu(I) dual catalytic
system, should make this method appealing to synthetic chemists.
These compounds were also synthesised by the ring opening of
epoxide and cyclisaiton using Cu(I). The wide applicability is
also amply proven by the diverse range of substrates used.
55 Finally, we have shown that this method is applicable to both aryl
and vinyl iodide reactants and reaction with aryl bromides is
sluggish.
O
41 (92%)
(from 1a)
Scheme 9
A possible pathway for the above sequential click reaction and
intramolecular cyclisation involves two steps. First step involves
the formation of 1,2,3-triazole from alkyne and azide via a
20 dinuclear copper intermediate.1d This pathway is supported by a
very recent paper of Worrell13 et al. The second step involves the
formation of C-O bond; here, we performed a series of reactions
starting from 4 (Scheme 10) to check the effect of different
conditions. There was no reaction when base (condition a) or
25 copper catalyst (condition b) was absent. Notably, product 3 was
observed in 62% of yield without addition of ligand (condition c)
and in one-pot strategy we obtained 55% yield (cf. Scheme 1
above). In this case, the triazole and OH moieties act as bidentate
ligand (similar to hydroxymethyl benzotriazole which is used in
30 copper-catalysis14 as a ligand). To achieve good yields in this
Experimental Section
The general experimental conditions and synthesis of the
60 precursors are described in the supplementary material.
General Procedure
An oven-dried Schlenk tube with a magnetic stirring bar was
charged with CuI (10 mol%), picolinic acid (20 mol%), cesium
carbonate (3.0 equiv), and toluene (1 mL) under nitrogen
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atmosphere. Later, 1-azido-3-(2-iodophenoxy)propan-2-ol (2a,
0.5 mmol) and phenyl acetylene (0.55 mmol) were added via 60 CDCl3) δ 148.3, 142.9, 142.0, 138.3, 129.6, 127.6, 125.8, 122.2,
6.0 Hz, 1H, CHaHb), 2.93 (s, 3H, Ar-CH3); 13C NMR (100 MHz,
syringe, and the contents heated at 120 °C (oil bath temperature)
for 12 h. The mixture was then cooled to ambient temperature,
diluted with 2-3 mL of ethyl acetate, passed through a plug of
celite, and then washed with 20-30 mL of ethyl acetate. The
120.7, 117.6, 71.4 (OCH), 65.0 (OCH2), 50.2 (NCH2), 21.4
(CH3); HRMS (ESI) Calc. for C18H17N3O2Na [M+Na]+ 330.1219,
Found: 330.1218.
5
o
Compound 8: Yield 0.139 g (82%); mp 154-156 C; IR (KBr,
organic layer was evaporated and the residue purified by column 65 cm–1) 3086, 1597, 1518, 1501, 1462, 1350, 1279, 1049, 853, 750;
chromatography on silica gel by using hexane/ethyl acetate
(75/25) as eluent to afford the desired product 3. Compounds 6-
1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 8.8 Hz, 2H, Ar-H),
8.01-8.03 (m, 3H, triazole-H+Ar-H), 6.89-6.95 (m, 4H, Ar-H),
4.68-4.83 (m, 3H, OCH+CH2), 4.39 (dd, J ~ 11.6 and 2.0 Hz, 1H,
CHaHb), 3.96 (dd, J ~11.6 and 6.0 Hz, 1H, CHaHb); 13C NMR
10 32 were obtained using the same molar quantities in all the cases.
o
Compound 3: Yield 0.130 g (89%); mp 118-120 C; IR (KBr,
1
cm–1) 3084, 1595, 1499, 1277, 1204, 1046, 766; H NMR (400 70 (100 MHz, CDCl3) δ 147.4, 146.0, 142.7, 141.8, 136.6, 126.3,
MHz, CDCl3) δ 7.89 (s, 1H, triazole-H), 7.85 (dd, J ~ 8.0 and 1.2
Hz, 2H, Ar-H), 7.44 (t, J ~ 8.0 Hz, 2H, Ar-H), 7.34-7.37 (m, 1H,
15 Ar-H), 6.88-6.94 (m, 4H, Ar-H), 4.72-4.75 (m, 2H, CH2), 4.66-
4.69 (m, 1H, OCH), 4.37 (dd, J = 11.6 and 2.0 Hz, 1H, CHaHb),
124.4, 122.5, 122.33, 122.27, 117.6, 117.4, 71.2 (OCH), 64.8
(OCH2), 50.4 (NCH2); HRMS (ESI) Calc. for C17H15N4O4
[M+H]+ 339.1094, Found: 339.1092.
o
Compound 9: Yield 0.128 g (80%); mp 108-110 C; IR (KBr,
3.94 (dd, J = 11.6 and 6.0 Hz, 1H, CHaHb); 13C NMR (100 MHz, 75 cm–1) 3138, 2916, 1688, 1595, 1497, 1466, 1271, 1198, 1109,
1
CDCl3) δ 148.1, 142.8, 142.0, 130.4, 128.9, 128.3, 125.8, 122.2,
121.1, 117.5, 71.3 (OCH), 64.9 (OCH2), 50.2 (NCH2); HRMS
20 (ESI) Calc. for C17H16N3O2 [M+H]+ 294.1243, Found: 294.1245.
1038, 828, 777, 745; H NMR (400 MHz, CDCl3) δ 10.4 (s, 1H,
CHO), 8.04 (d, J = 7.2 Hz, 1H, Ar-H), 7.98 (s, 1H, triazole-H),
7.74 (d, J ~ 7.2 Hz, 1H, Ar-H), 7.66-7.70 (m, 1H, Ar-H), 7.54 (t,
J ~ 7.6 Hz, 1H, Ar-H), 6.89-6.94 (m, 4H, Ar-H), 4.69-4.85 (m,
o
Compound 4: Yield 0.196 g (93%); mp 139-141 C; IR (KBr,
cm–1) 3385, 1582, 1474, 1441, 1281, 1231, 1123, 1047, 760, 739; 80 3H, OCH+CH2), 4.40 (dd, J = 11.6 and 2.4 Hz, 1H, CHaHb), 3.99
1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H, triazole-H), 7.77-7.80
(m, 3H, Ar-H), 7.35-7.43 (m, 2H, Ar-H), 7.29-7.33 (m, 2H, Ar-
25 H), 6.76-6.82 (m, 2H, Ar-H), 4.82 (dd, J = 14.0 and 4.0 Hz, 1H,
CHaHb), 4.71 (dd, J = 14.0 and 6.4 Hz, 1H, CHaHb), 4.56-4.58
(dd, J ~ 11.6 and 6.0 Hz, 1H, CHaHb); 13C NMR (100 MHz,
CDCl3) δ 192.4, 145.0, 142.8, 141.8, 133.8, 132.7, 130.1, 129.1,
128.8, 124.8, 122.3, 117.6, 117.5, 71.3 (OCH), 64.9 (OCH2), 50.4
(NCH2); HRMS (ESI) Calc. for C18H16N3O3 [M+H]+ 322.1192,
(m, 1H, CHOH), 4.01-4.08 (m, 2H, CH2), 3.54 (br s, 1H, OH); 85 Found: 322.1194.
o
13C NMR (100 MHz, CDCl3) δ 156.4, 147.6, 139.4, 130.2, 129.8,
128.9, 128.3, 125.7, 123.5, 121.5, 112.6, 86.6 (CI), 69.9 (OCH),
30 68.7 (OCH2), 53.1 (NCH2); HRMS (ESI) Calc. for C17H17IN3O2
Compound 10: Yield 0.144 g (84%); mp 129-131 C; IR (KBr,
cm–1) 3052, 2912, 1591, 1497, 1466, 1265, 1204, 1119, 1053,
1038, 903, 799, 754; 1H NMR (400 MHz, CDCl3) δ 8.36-8.38 (m,
1H, Ar-H), 7.95 (s, 1H, triazole-H), 7.90-7.93 (m, 2H, Ar-H),
[M+H]+ 422.0366, Found: 422.0368.
o
Compound 5: Yield 0.045 g (35%); mp 138-140 C; IR (KBr, 90 7.75 (d, J = 7.2 Hz, 1H, Ar-H), 7.51-7.56 (m, 3H, Ar-H), 6.89-
cm–1) 3134, 1682, 1573, 1474, 1441, 1277, 1041, 997, 751, 690;
1H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H, triazole-H), 7.79-7.88
35 (m, 3H, Ar-H), 7.62-7.65 (m, 1H, Ar-H), 7.32-7.47 (m, 4H, Ar-
H), 6.88 (d, J = 8.4 Hz, 1H, Ar-H), 6.77-6.80 (m, 1H, =C-H),
6.95 (m, 4H, Ar-H), 4.77-4.85 (m, 2H, CH2), 4.71-4.74 (m, 1H,
OC-H), 4.41 (dd, J = 11.6 and 2.0 Hz, 1H, CHaHb), 4.01 (dd, J =
11.6 and 6.0 Hz, 1H, CHaHb); 13C NMR (100 MHz, CDCl3) δ
147.2, 142.9, 142.0, 134.0, 131.2, 129.1, 128.6, 127.9, 127.4,
6.54-6.59 (m, 1H, =C-H), 4.81 (m, 2H, OCH2); 13C NMR (100 95 126.8, 126.1, 125.42, 125.37, 124.1, 122.2, 117.6, 117.5, 71.5
MHz, CDCl3) δ 156.6, 148.1, 139.8, 131.7, 130.1, 129.7, 129.0,
126.5, 125.9, 123.5, 117.3, 116.7, 112.6, 86.8 (CI), 66.5 (OCH2);
40 HRMS (ESI) Calc. for C17H15IN3O [M+H]+ 404.0261, Found:
(OCH), 65.0 (OCH2), 50.3 (NCH2); HRMS (ESI) Calc. for
C21H18N3O2 [M+H]+ 344.1400, Found: 344.1398.
o
Compound 11: Yield 0.168 g (75%); mp 102-104 C; IR (KBr,
404.0263.
cm–1) 3167, 2922, 1593, 1495, 1458, 1437, 1260, 1217, 1123,
o
Compound 6: Yield 0.138 g (85%); mp 116-118 C; IR (KBr, 100 1051, 1019, 928, 828, 747; 1H NMR (400 MHz, CDCl3) δ 7.85 (s,
cm–1) 3115, 2936, 1615, 1561, 1497, 1456, 1362, 1248, 1177,
1103, 1024, 910, 837, 752; 1H NMR (400 MHz, CDCl3) δ 7.81 (s,
45 1H, triazole-H), 7.77 (dd, J = 6.8 and 2.0 Hz, 2H, Ar-H), 6.88-
6.99 (m, 6H, Ar-H), 4.70-4.76 (m, 2H, CH2), 4.63-4.67 (m, 1H,
1H, triazole-H), 7.77 (dd, J = 8.0 and 1.6 Hz, 1H, Ar-H), 7.29-
7.33 (m, 1H, Ar-H), 6.98 (d, J = 8.0 Hz, 1H, Ar-H), 6.89 (br, 4H,
Ar-H), 6.72-6.76 (m, 1H, Ar-H), 5.32 (s, 2H, OCH2), 4.60-4.72
(m, 3H, OCH + CH2), 4.34 (dd, J ~ 11.6 and 2.0 Hz, 1H, CHaHb),
OCH), 4.36 (dd, J = 11.6 and 2.0 Hz, 1H, CHaHb), 3.93 (dd, J = 105 3.89 (dd, J = 11.6 and 6.0 Hz, 1H, CHaHb); 13C NMR (100 MHz,
11.6 and 6.0 Hz, 1H, CHaHb), 3.85 (s, 3H, Ar-OCH3);13C NMR
(100 MHz, CDCl3) δ 159.8, 148.0, 142.9, 142.0, 127.2, 123.1,
50 122.2, 120.2, 117.6, 117.5, 114.3, 71.4 (OCH), 65.0 (OCH2), 55.4
(OCH3), 50.2 (NCH2); HRMS (ESI) Calc. for C18H18N3O3
[M+H]+ 324.1349, Found: 324.1347.
CDCl3) δ 156.7, 144.5, 142.8, 141.8, 139.6, 129.7, 124.4, 123.3,
122.2, 122.1, 117.6, 117.5, 112.9, 86.8 (CI), 71.3 (OCH), 64.9
(OCH2), 63.6 (OCH2), 50.2 (NCH2); HRMS (ESI) Calc. for
C18H17IN3O3 [M+H]+ 450.0315, Found: 450.0317.
o
110 Compound 12: Yield 0.127 g (79%); mp 149-151 C; IR (KBr,
o
Compound 7: Yield 0.134 g (87%); mp 138-140 C; IR (KBr,
cm–1) 3129, 2924, 1645, 1595, 1526, 1493, 1254, 1080, 905, 829,
1
1
cm–1) 3088, 1595, 1499, 1454, 1277, 1204, 1046, 820, 747; H
752; H NMR (400 MHz, CDCl3) δ 8.41-8.44 (m, 2H, Ar-H),
55 NMR (400 MHz, CDCl3) δ 7.85 (s, 1H, triazole-H), 7.73 (d, J =
8.4 Hz, 2H, Ar-H), 7.25 (d, J = 8.4 Hz, 2H, Ar-H), 6.89-6.94 (m,
8.39 (s, 1H, triazole-H), 7.61-7.65 (m, 1H, Ar-H), 7.52-7.56 (m,
2H, Ar-H), 6.89-6.95 (m, 4H, Ar-H), 4.67-4.85 (m, 3H, OCH +
4H, Ar-H), 4.71-4.74 (m, 2H, CH2), 4.67-4.68 (m, 1H, O-CH), 115 CH2), 4.39 (dd, J ~ 11.6 and 2.0 Hz, 1H, CHaHb), 3.98 (dd, J =
4.37 (dd, J = 11.6 and 2.0 Hz, 1H, CHaHb), 3.94 (dd, J = 11.6 and
11.6 and 6.0 Hz, 1H, CHaHb); 13C NMR (100 MHz, CDCl3) δ
6
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DOI: 10.1039/C3OB41332B
185.7, 148.4, 142.7, 141.7, 136.5, 133.5, 130.7, 129.9, 128.5,
2H, Ar-H), 6.84 (d, J = 8.4 Hz, 1H, Ar-H), 4.63-4.74 (m, 3H,
122.4, 117.7, 117.6, 71.1 (OCH), 64.8 (OCH2), 50.5 (NCH2); 60 OCH + CH2), 4.34 (dd, J = 11.6 and 2.0 Hz, 1H, CHaHb), 3.90
HRMS (ESI) Calc. for C18H16N3O3 [M+H]+ 322.1192, Found:
322.1189.
(dd, J = 11.6 and 6.4 Hz, 1H, CHaHb), 1.29 (s, 9H, C(CH3)3); 13
C
NMR (100 MHz, CDCl3) δ 148.2, 145.7, 141.4, 140.4, 130.5,
129.0, 128.4, 125.9, 121.1, 119.2, 116.9, 114.4, 71.5 (OCH), 65.0
(OCH2), 50.4 (NCH2), 34.4, 31.5; HRMS (ESI) Calc. for
o
5
Compound 13: Yield 0.116 g (78%); mp 106-108 C; IR (KBr,
cm–1) 3156, 3044, 2924, 1593, 1497, 1462, 1298, 1269, 1051,
1
1036, 905, 839, 750; H NMR (400 MHz, CDCl3) δ 7.52 (s, 1H, 65 C21H24N3O2 [M+H]+ 350.1869, Found: 350.1867.
o
triazole-H), 6.88-6.92 (m, 4H, Ar-H), 6.83-6.54 (m, 1H, alkene-
H), 4.59-4.67 (m, 3H, OCH + CH2), 4.32 (dd, J ~ 11.6 and 2.0
Compound 18: Yield 0.134 g (78%); mp 126-128 C; IR (KBr,
cm–1) 3127, 2922, 1603, 1499, 1439, 1318, 1217, 1074, 1028,
859, 766, 693; 1H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H,
triazole-H), 7.84-7.86 (m, 2H, Ar-H), 7.35-7.46 (m, 3H, Ar-H),
10 Hz, 1H, CHaHb), 3.87 (dd, J = 11.6 and 6.0 Hz, 1H, CHaHb),
2.28-2.41 (m, 2H, CH2), 2.20-2.23 (m, 2H, CH2), 1.66-1.79 (m,
4H, 2 CH2); 13C NMR (100 MHz, CDCl3) δ 149.8, 142.8, 142.0, 70 6.58-6.59 (m, 2H, Ar-H), 4.61-4.74 (m, 3H, OCH + CH2), 4.35
127.1, 125.4, 122.0, 119.7, 117.4, 71.4 (OCH), 64.9 (OCH2), 50.0
(NCH2), 26.4, 25.3, 22.4, 22.2; HRMS (ESI) Calc. for
15 C17H20N3O2 [M+H]+ 298.1556, Found: 298.1554.
(dd, J = 11.6 and 2.0 Hz, 1H, CHaHb), 3.93 (dd, J = 11.6 and 6.0
Hz, 1H, CHaHb), 2.17 and 2.24 (2 s, 6H, 2 CH3); 13C NMR (100
MHz, CDCl3) δ 148.1, 141.3, 138.7, 130.9, 130.4, 128.9, 128.3,
126.7, 125.8, 124.2, 121.1, 115.2, 71.3 (OCH), 64.9 (OCH2), 50.3
Compound 14: Yield 0.118 g (72%); mp 75-77 oC; IR (KBr, cm–
1) 3063, 2924, 2851, 1597, 1501, 1464, 1279, 1053, 862, 743; 1H 75 (NCH2), 20.7 and 15.4 (2 CH3); HRMS (ESI) Calc. for
NMR (400 MHz, CDCl3) δ 7.40 (s, 1H, triazole-H), 6.89-6.92 (m,
4H, Ar-H), 4.63-4.66 (m, 2H, CH2), 4.58-4.61 (m, 1H, OCH),
20 4.32 (dd, J = 11.6 and 2.0 Hz, 1H, CHaHb), 3.87 (dd, J = 11.6 and
6.0 Hz, 1H, CHaHb), 2.72 (t, J = 6.8 Hz, 2H, CH2), 1.66-1.69 (m,
C19H19N3O2Na [M+Na]+ 344.1375, Found: 344.1377.
o
Compound 19: Yield 0.192 g (86%); mp 163-165 C; IR (KBr,
cm–1) 3136, 2918, 1588, 1480, 1449, 1340, 1242, 1159, 1066,
1
910, 848, 760; H NMR (400 MHz, CDCl3) δ 7.82-7.84 (m, 2H,
2H, CH2), 1.27-1.33 (m, 10H, 5 CH2), 0.88 (t, J = 6.6 Hz, 3H, 80 Ar-H), 7.81 (s, 1H, triazole-H), 7.78 (dd, J = 8.4 and 1.6 Hz, 1H,
CH3); 13C NMR (100 MHz, CDCl3) δ 148.9, 142.9, 142.1, 122.1,
122.0, 117.5, 117.4, 71.5 (OCH), 65.0 (OCH2), 50.0 (NCH2),
25 31.9, 29.5, 29.4, 29.3, 25.7, 22.7, 14.2 (CH3); HRMS (ESI) Calc.
Ar-H), 7.52 (d, J = 8.0 Hz, 2H, Ar-H), 7.44 (t, J ~ 7.6 Hz, 2H,
Ar-H), 7.35 (t, J ~ 7.6 Hz, 1H, Ar-H), 7.22 (d, J = 8.4 Hz, 2H,
Ar-H), 7.08 (t, J = 7.2 Hz, 1H, Ar-H), 6.96 (t, J = 7.2 Hz, 1H, Ar-
H), 6.87 (dd, J ~ 8.4 and 1.2 Hz, 1H, Ar-H), 4.60 (d, J = 4.8 Hz,
for C19H28N3O2 [M+H]+ 330.2182 Found: 330.2178.
o
Compound 15: Yield 0.139 g (81%); mp 148-150 C; IR (KBr, 85 2H, NCH2), 4.33 (dd, J = 14.4 and 2.4 Hz, 1H, NCHaHb), 3.83-
cm–1) 3083, 1634, 1603, 1474, 1395, 1358, 1260, 1105, 1051,
3.89 (m, 1H, OCH), 3.14 (dd, J = 14.4 and 9.6 Hz, 1H, NCHaHb),
2.37 (s, 3H, ArCH3); 13C NMR (100 MHz, CDCl3) δ 148.1,
145.9, 144.7, 135.3, 130.3, 130.2, 129.0, 128.5, 127.2, 126.4,
125.8, 124.4, 123.5, 121.7, 120.9, 117.4, 70.3 (OCH), 51.4
1
978, 808, 768, 693; H NMR (400 MHz, CDCl3) δ 8.01 (d, J =
30 8.4 Hz, 1H, Ar-H), 7.84 (s, 1H, triazole-H), 7.78-7.83 (m, 3H,
Ar-H), 7.45-7.52 (m, 1H, Ar-H), 7.40-7.45 (m, 4H, Ar-H), 7.33-
7.37 (m, 1H, Ar-H), 7.13 (dd, J ~ 8.4 and 2.8 Hz, 1H, Ar-H), 90 (NCH2), 45.8 (NCH2), 21.7 (ArCH3); HRMS (ESI) Calc. for
4.78-4.88 (m, 3H, OCH + CH2), 4.48 (dd, J ~ 11.6 and 2.0 Hz,
1H, CHaHb), 4.12 (dd, J = 11.6 and 4.8 Hz, 1H, CHaHb); 13C
35 NMR (100 MHz, CDCl3) δ 148.2, 138.4, 134.6, 130.4, 129.9,
129.0, 128.4, 127.9, 126.3, 125.8, 125.5, 124.7, 121.9, 121.1,
C24H23N4O3S [M+H]+ 447.1492, Found: 447.1489.
o
Compound 20: Yield 0.173 g (77%); mp 168-170 C; IR (KBr,
cm–1) 3134, 2920, 1655, 1584, 1479, 1447, 1342, 1238, 1167,
1
1068, 942, 856, 762, 657, 564; H NMR (400 MHz, CDCl3) δ
119.8, 118.3, 71.6 (OCH), 65.0 (OCH2), 50.1 (NCH2); HRMS 95 7.76 (d, J ~ 8.0 Hz, 1H, Ar-H), 7.48 (d, J = 8.0 Hz, 2H, Ar-H),
(ESI) Calc. for C21H17N3O2Na [M+Na]+ 366.1219, Found:
366.1217.
7.43 (s, 1H, triazole-H), 7.22 (d, J ~ 8.0 Hz, 2H, Ar-H), 7.07 (t, J
~ 7.6 Hz, 1H, Ar-H), 6.95 (t, J = 7.6 Hz, 1H, Ar-H), 6.84 (d, J =
8.0 Hz, 1H, Ar-H), 6.52 (s, 1H, cyclohexenyl-H), 4.51 (d, J = 4.8
Hz, 2H, NCH2), 4.29 (dd, J ~ 14.4 and 2.4 Hz, 1H, NCHaHb),
o
40 Compound 16: Yield 0.134 g (82%); mp 137-140 C; IR (KBr,
cm–1) 3094, 2924, 1588, 1493, 1462, 1275, 1200, 1084, 1038,
1
936, 856, 766, 693; H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H, 100 3.75-3.77 (m, 1H, OCH), 3.05 (dd, J = 14.4 and 9.6 Hz, 1H,
triazole-H), 7.84 (d, J = 8.0 Hz, 2H, Ar-H), 7.45 (t, J ~ 7.4 Hz,
2H, Ar-H), 7.36 (t, J ~ 7.4 Hz, 1H, Ar-H), 6.93-6.94 (m, 1H, Ar-
45 H), 6.82-6.88 (m, 2H, Ar-H), 4.64-4.73 (m, 3H, OCH + CH2),
4.36 (dd, J ~ 11.6 and 2.0 Hz, 1H, CHaHb), 3.91 (dd, J ~ 11.6 and
NCHaHb), 2.38 (br s, 5H, CH2+ArCH3), 2.19-2.20 (m, 2H, CH2),
1.65-1.78 (m, 4H, 2 CH2); 13C NMR (100 MHz, CDCl3) δ 149.8,
145.9, 144.6, 135.2, 130.1, 127.2, 127.0, 126.3, 125.5, 124.4,
123.4, 121.6, 119.6, 117.4, 70.2 (OCH), 51.2 (NCH2), 45.7
6.0 Hz, 1H, CHaHb); 13C NMR (100 MHz, CDCl3) δ 148.3, 142.5, 105 (NCH2), 26.4, 25.3, 22.4, 22.2, 21.6 (ArCH3); HRMS (ESI) Calc.
141.6, 130.3, 129.0, 128.5, 126.7, 125.9, 122.2, 121.0, 118.4,
117.6, 71.6 (OCH), 64.9 (OCH2), 50.1 (NCH2); HRMS (ESI)
50 Calc. for C17H15ClN3O2 [M+H]+ 328.0854 and 330.0824, Found:
for C24H27N4O3S [M+H]+ 451.1805, Found: 451.1806. This
compound was crystallized from dichloromethane/hexane (2:1)
mixture at 25 oC. X-ray structure was determined for this
compound.
328.0853 and 330.0817. This compound was crystallized from
o
dichloromethane/hexane (1:1) mixture at 25 C. X-ray structure 110 Compound 21: Yield 0.183 g (76%); mp 68-70 oC; IR (KBr, cm–
was determined for this compound.
1) 3162, 2915, 2849, 1594, 1479, 1449, 1348, 1233, 1162, 1068,
926, 800, 762, 663, 575; 1H NMR (400 MHz, CDCl3) δ 7.77 (dd,
J ~ 8.0 and 1.6 Hz, 1H, Ar-H), 7.50 (d, J = 8.4 Hz, 2H, Ar-H),
7.32 (s, 1H, triazole-H), 7.24 (d, J = 8.4 Hz, 2H, Ar-H), 7.05-7.09
o
Compound 17: Yield 0.150 g (86%); mp 166-169 C; IR (KBr,
55 cm–1) 3092, 2963, 1582, 1503, 1466, 1310, 1269, 1231, 1088,
1073, 918, 764; 1H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H,
triazole-H), 7.85 (dd, J = 8.4 and 1.2 Hz, 2H, Ar-H), 7.45 (t, J ~ 115 (m, 1H, Ar-H ), 6.93-6.97 (m, 1H, Ar-H), 6.84 (dd, J = 8.0 and
7.4 Hz, 2H, Ar-H), 7.36 (t, J ~ 7.4 Hz, 1H, Ar-H), 6.91-6.95 (m,
1.2 Hz, 1H, Ar-H), 4.50 (d, J = 4.8 Hz, 2H, NCH2), 4.28 (dd, J =
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DOI: 10.1039/C3OB41332B
14.4 and 2.4 Hz, 1H, NCHaHb), 3.81-3.85 (m, 1H, OCH), 3.05
H), 7.36 (t, J ~ 7.6 Hz, 1H, Ar-H), 7.02-7.09 (m, 2H, Ar-H), 6.86-
(dd, J ~ 14.4 and 9.6 Hz, 1H, NCHaHb), 2.70 (t, J ~ 7.4 Hz, 2H, 60 6.92 (m, 2H, Ar-H), 4.73-4.82 (m, 3H, CH2+OCH), 3.14 (dd, J ~
CH2), 2.39 (s, 3H, ArCH3), 1.62-1.69 (m, 2H, CH2), 1.26-1.31
(m, 10H, 5 CH2), 0.87 (t, J ~ 6.4 Hz, 3H, CH3); 13C NMR (100
MHz, CDCl3) δ 148.8, 145.9, 144.7, 135.3, 130.2, 127.2, 126.3,
124.4, 123.5, 122.0, 121.6, 117.4, 70.2 (OCH), 51.2 (NCH2), 45.8
13.2 and 1.6 Hz, 1H, CHaHb), 2.92 (dd, J ~ 13.2 and 7.6 Hz, 1H,
CHaHb); 13C NMR (100 MHz, CDCl3) δ 150.3, 148.0, 130.4,
128.9, 128.3, 127.5, 126.1, 125.8, 122.2, 121.0, 118.6, 116.9,
72.5 (OCH), 53.1 (NCH2), 26.9 (SCH2); HRMS (ESI) Calc. for
5
(NCH2), 31.9, 29.44, 29.39, 29.3, 25.7, 22.7, 21.7 (ArCH3), 14.2; 65 C17H16N3OS [M+H]+ 310.1015, Found: 310.1012.
HRMS (ESI) Calc. for C26H35N4O3S [M+H]+ 483.2431, Found:
Compound 26: Yield 0.125 g (80 %); mp 98-100 C; IR (KBr,
o
483.2428.
cm–1) 3140, 2931, 2855, 1737, 1567, 1479, 1447, 1271, 1222,
1074, 1019, 904, 800, 751; 1H NMR (400 MHz, CDCl3) δ 7.54 (s,
1H, triazole-H), 7.00-7.06 (m, 2H, Ar-H), 6.83-6.89 (m, 2H, Ar-
o
10 Compound 22: Yield 0.189 g (82%); mp 176-178 C; IR (KBr,
cm–1) 3053, 2915, 1578, 1495, 1430, 1358, 1260, 1161, 1062,
1
931, 810, 762, 668; H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 70 H), 6.52-6.57 (m, 1H, cyclohexenyl-H), 4.64-4.69 (m, 3H,
8.4 Hz, 2H, Ar-H), 7.78 (s, 1H, triazole-H), 7.65 (d, J = 8.4 Hz,
1H, Ar-H), 7.50 (d, J = 8.0 Hz, 2H, Ar-H), 7.45 (t, J ~ 7.6 Hz,
15 2H, Ar-H), 7.36 (t, J ~ 7.6 Hz, 1H, Ar-H), 7.22 (d, J = 8.0 Hz,
2H, Ar-H), 6.78 (dd, J = 8.4 and 1.6 Hz, 1H, Ar-H), 6.68 (br, 1H,
CH2+OCH), 2.85 (dd, J = 13.2 and 7.2 Hz, 1H, CHaHb), 3.06 (dd,
J = 13.2 and 1.6 Hz, 1H, CHaHb), 2.19-2.39 (m, 4H, 2 CH2),
1.65-1.78 (m, 4H, 2 CH2); 13C NMR (100 MHz, CDCl3) δ 150.3,
149.7, 127.5, 127.1, 126.0, 125.3, 122.1, 119.7, 118.5, 116.9,
Ar-H), 4.56-4.58 (m, 2H, NCH2), 4.30 (dd, J = 14.4 and 2.4 Hz, 75 72.5 (OCH), 52.9 (NCH2), 26.9 (SCH2), 26.4, 25.3, 22.4, 22.2;
1H, NCHaHb), 3.77-3.82 (m, 1H, O-CH), 3.11 (dd, J ~14.4 and
9.6 Hz, 1H, NCHaHb), 2.28 and 2.37 (2 s, 6H, 2 CH3); 13C NMR
20 (100 MHz, CDCl3) δ 148.1, 145.7, 144.6, 136.7, 135.2, 130.3,
130.2, 129.0, 128.5, 127.3, 125.8, 124.3, 122.7, 120.9, 120.8,
HRMS (ESI) Calc. for C17H20N3OS [M+H]+ 314.1328, Found:
314.1327.
Compound 27: Yield 0.133 g (77%); mp 70-72 oC; IR (KBr, cm–
1) 3112, 3057, 2920, 2844, 1573, 1474, 1436, 1293, 1233, 1052,
117.7, 70.1 (OCH), 51.5 (NCH2), 45.9 (NCH2), 20.9 and 21.7 (2 80 997, 866, 734; 1H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H,
CH3); HRMS (ESI) Calc. for C25H24N4O3SNa [M+Na]+
triazole-H), 7.01-7.07 (m, 2H, Ar-H), 6.83-6.91 (m, 2H, Ar-H),
4.65-4.72 (m, 3H, CH2+OCH), 3.10 (dd, J ~ 13.2 and 1.6 Hz, 1H,
CHaHb), 2.86 (dd, J ~ 13.2 and 6.4 Hz, 1H, CHaHb), 2.72 (t, J ~
7.6 Hz, 2H, CH2), 1.66-1.68 (m, 2H, CH2), 1.27-1.32 (m, 10H, 5
483.1467, Found: 483.1465.
o
25 Compound 23: Yield 0.181 g (78%); mp 170-173 C; IR (KBr,
cm–1) 3139, 2920, 1583, 1501, 1435, 1353, 1260, 1161, 1057,
1
932, 816, 673, 531; H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 85 CH2), 0.86-0.89 (m, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ
8.4 Hz, 1H, Ar-H), 7.48 (d, J = 8.4 Hz, 2H, Ar-H), 7.42 (s, 1H,
triazole-H), 7.22 (d, J = 8.4 Hz, 2H, Ar-H), 6.77 (dd, J = 8.4 and
30 1.6 Hz, 1H, Ar-H), 6.65-6.66 (m, 1H, Ar-H), 6.52-6.54 (m, 1H,
=CH), 4.49 (d, J = 4.8 Hz, 2H, NCH2), 4.26 (dd, J = 14.4 and 2.4
150.4, 148.8, 127.5, 126.1, 122.2, 122.0, 118.6, 117.0, 72.6
(OCH), 52.9 (NCH2), 31.9, 29.5, 29.4, 29.3, 27.0 (SCH2), 25.7,
22.7, 14.2; HRMS (ESI) Calc. for C19H28N3OS [M+H]+
346.1954, Found: 346.1955.
o
Hz, 1H, NCHaHb), 3.68-3.73 (m, 1H, OCH), 3.03 (dd, J ~ 14.4 90 Compound 28: Yield 0.118 g (77%); mp 125-127 C; IR (KBr,
and 9.6 Hz, 1H, NCHaHb), 2.38-2.39 (m, 5H, CH2+ArCH3), 2.28
(s, 3H, CH3), 2.20-2.22 (m, 2H, CH2), 1.67-1.81 (m, 4H, 2 CH2);
35 13C NMR (100 MHz, CDCl3) δ 149.7, 145.7, 144.5, 136.6, 135.2,
130.1, 127.2, 127.0, 125.5, 124.3, 122.5, 120.7, 119.6, 117.6,
cm–1) 3127, 2940, 2845, 1602, 1582, 1487, 1454, 1248, 1194,
1105, 1082, 905, 766, 694; 1H NMR (400 MHz, CDCl3) δ 8.00 (s,
1H, triazole-H), 7.90 (dd, J = 8.4 and 1.2 Hz, 2H, Ar-H), 7.46 (t,
J ~ 7.6 Hz, 2H, Ar-H), 7.37-7.38 (m, 1H, Ar-H), 7.05-7.19 (m,
70.0 (OCH), 51.2 (NCH2), 45.8 (NCH2), 26.3, 25.3, 22.4, 22.2, 95 3H, Ar-H), 6.84 (d, J = 8.0 Hz, 1H, Ar-H), 4.68 (s, 2H, OCH2),
21.6, 20.9; HRMS (ESI) Calc. for C25H29N4O3S [M+H]+
465.1961, Found: 465.1960.
4.57-4.62 (m, 2H, CH2), 4.34-4.35 (m, 1H, OCH), 4.21 (dd, J =
12.8 and 1.2 Hz, 1H, CHaHb), 3.74 (dd, J = 12.8 and 8.4 Hz, 1H,
CHaHb); 13C NMR (100 MHz, CDCl3) δ 157.3, 147.9, 132.3,
130.6, 129.6, 129.3, 129.0, 128.3, 125.8, 124.2, 121.1, 121.0,
40 Compound 24: Yield 0.184 g (74%); mp 78-80 oC; IR (KBr, cm–
1) 3117, 2920, 2854, 1588, 1501, 1451, 1358, 1260, 1161, 1057,
1
931, 816, 668, 536; H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 100 80.7 (OCH2), 74.3 (OCH), 73.5 (OCH2), 51.2 (NCH2); HRMS
8.4 Hz, 1H, Ar-H), 7.49 (d, J = 8.4 Hz, 2H, Ar-H), 7.31 (s, 1H,
triazole-H), 7.23-7.27 (m, 2H, Ar-H), 6.77 (dd, J = 8.4 and 1.2
45 Hz, 1H, Ar-H), 6.66 (s, 1H, Ar-H), 4.48 (d, J = 4.8 Hz, 2H,
NCH2), 4.25 (dd, J = 14.4 and 2.4 Hz, 1H, NCHaHb), 3.74-3.76
(ESI) Calc. for C18H17N3O2Na [M+Na]+ 330.1219, Found:
330.1218.
o
Compound 29: Yield 0.140 g (83%); mp 140-142 C; IR (KBr,
cm–1) 3106, 2845, 1605, 1582, 1503, 1487, 1454, 1250, 1107,
(m, 1H, OCH), 3.01 (dd, J ~ 14.4 and 9.6 Hz, 1H, NCHaHb), 2.70 105 1032, 907, 822; 1H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H,
(t, J ~ 7.8 Hz, 2H, CH2), 2.28 and 2.39 (2 s, 6H, 2 ArCH3), 1.62-
1.68 (m, 2H, CH2), 1.26-1.31 (m, 10H, 5 CH2), 0.87 (t, J = 6.8
50 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ 148.8, 145.7,
144.5, 136.6, 135.2, 130.1, 127.2, 124.3, 122.5, 122.0, 120.7,
triazole-H), 7.81 (d, J ~ 8.4 Hz, 2H, Ar-H), 7.16-7.21 (m, 2H, Ar-
H), 7.05 (t, J ~ 7.6 Hz, 1H, Ar-H), 6.99 (d, J = 8.4 Hz, 2H, Ar-H),
6.85 (d, J = 8.0 Hz, 1H, Ar-H), 4.68 (s, 2H, OCH2), 4.56-4.61 (m,
2H, CH2), 4.34-4.35 (m, 1H, OCH), 4.20 (d, J = 12.8 Hz, 1H,
117.6, 70.0 (OCH), 51.2 (NCH2), 45.9 (NCH2), 31.9, 29.43, 29.39, 110 CHaHb), 3.86 (s, 3H, OCH3), 3.74 (dd, J = 12.8 and 8.4 Hz, 1H,
29.3, 25.7, 22.7, 21.7, 20.9, 14.2; HRMS (ESI) Calc. for
C27H37N4O3S [M+H]+ 497.2587, Found: 497.2588.
CHaHb); 13C NMR (100 MHz, CDCl3) δ 159.7, 157.4, 147.8,
132.4, 129.6, 129.3, 127.1, 124.2, 123.3, 121.0, 120.3, 114.4,
80.8 (OCH2), 74.3 (OCH), 73.5 (OCH2), 55.4 (OCH3), 51.2
(NCH2); HRMS (ESI) Calc. for C19H19N3O3Na [M+Na]+
55 Compound 25: Yield 0.130 g (84%); mp 84-86 oC; IR (KBr, cm–
1) 3140, 2948, 2915, 1611, 1573, 1468, 1436, 1260, 1222, 1079,
1
1047, 915, 756, 690; H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H, 115 360.1324, Found: 360.1326.
o
triazole-H), 7.83-7.86 (m, 2H, Ar-H), 7.45 (t, J ~ 7.6 Hz, 2H, Ar-
Compound 30: Yield 0.127 g (72%); mp 169-171 C; IR (KBr,
8
| Journal Name, [year], [vol], 00–00
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Page 10 of 12
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DOI: 10.1039/C3OB41332B
cm–1) 3148, 2853, 1605, 1516, 1464, 1337, 1244, 1109, 1071,
853, 754; 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.8 Hz, 2H, 60 is doubled in the assignment; 13C NMR (100 MHz, CDCl3) δ
2.11 (m, 12H), due to the presence of isomers, number of protons
Ar-H), 8.16 (s, 1H, triazole-H), 8.06 (d, J = 8.8 Hz, 2H, Ar-H),
7.18-7.22 (m, 2H, Ar-H), 7.06 (t, J ~ 7.2 Hz, 1H, Ar-H), 6.82 (d,
J = 8.0 Hz, 1H, Ar-H), 4.59-4.72 (m, 4H, 2 CH2), 4.36-4.37 (m,
1H, OCH), 4.23 (dd, J ~ 12.8 and 1.6 Hz, 1H, CHaHb), 3.74 (dd, J
149.8, 148.0, 147.8, 147.1, 138.1, 129.6, 127.8, 127.7, 125.7,
120.8, 120.5, 108.9, 107.6, 75.0, 73.3, 72.3, 71.3, 69.6, 67.7,
66.6, 51.1, 50.2, 29.5, 29.3, 23.8, 23.6, 21.4, 20.5, due to the
presence of isomers, number of carbons is more in the spectrum;
5
= 12.8 and 8.4 Hz, 1H, CHaHb); 13C NMR (400 MHz, CDCl3) δ 65 HRMS (ESI) Calc. for C18H22N3O2 [M+H]+ 312.1713, Found:
157.2, 147.5, 145.7, 136.8, 132.3, 129.6, 129.4, 126.3, 124.5,
312.1712.
124.4, 122.6, 120.9, 80.5 (OCH2), 74.3 (OCH), 73.5 (OCH2),
Compound 35: (approx. 1:1 diastereomeric ratio),Yield 0.118 g
o
10 51.5 (NCH2); HRMS (ESI) Calc. for C18H16N4O4Na [M+Na]+
(69%); mp 142-145 C; IR (KBr, cm–1) 3151, 2948, 2860, 1731,
1
375.1070, Found: 375.1068. This compound was crystallized
1682, 1605, 1507, 1458, 1337, 1156, 1112, 855, 756; H NMR
o
from ethyl acetate/hexane (1:1) mixture at 25 C. X-ray structure 70 (400 MHz, CDCl3) δ 8.29-8.31 (m, 4H, Ar-H), 8.10 (s, 1H,
was determined for this compound.
triazole-H), 8.01-8.04 (m, 5H, Ar-H), 5.20-5.21 (m, 2H, =CH),
3.83-4.90 (m, 11H), 3.45-3.48 (m, 1H), 1.53-2.12 (m, 12H), due
to the presence of isomers, number of protons is doubled in the
assignment; 13C NMR (100 MHz, CDCl3) δ 149.6, 147.3, 147.0,
o
Compound 31: Yield 0.107 g (69%); mp 122-124 C; IR (KBr,
15 cm–1) 3148, 2936, 2834, 1580, 1487, 1454, 1267, 1248, 1227,
1
1121, 1071, 993, 907, 770; H NMR (400 MHz, CDCl3) δ 7.61
(s, 1H, triazole-H), 7.15-7,23 (m, 2H, Ar-H), 7.04-7.06 (m, 1H, 75 145.8, 145.6, 136.9, 126.2, 124.3, 122.6, 122.3, 109.0, 107.9,
Ar-H), 6.85 (d, J = 8.0 Hz, 1H, Ar-H), 6.56-6.57 (m, 1H,
cyclohexenyl-H), 4.66 (s, 2H, OCH2), 4.50-4.55 (m, 2H, CH2),
20 4.28-4.30 (m, 1H, OCH), 4.13 (dd, J = 12.8 and 1.6 Hz, 1H,
CHaHb), 3.70 (dd, J = 12.8 and 8.4 Hz, 1H, CHaHb), 2.21-2.43
(m, 4H, 2 CH2), 1.68-1.82 (m, 4H, 2 CH2); 13C NMR (100 MHz,
CDCl3) δ 157.4, 149.6, 132.3, 129.5, 129.3, 127.2, 125.2, 124.2,
121.0, 119.7, 80.7 (OCH2), 74.3 (OCH), 73.5 (OCH2), 51.1
25 (NCH2), 22.3, 22.5, 25.3 and 26.5 (4 CH2); HRMS (ESI) Calc.
for C18H22N3O2 [M+H]+ 312.1713, Found: 312.1711.
74.9, 73.2, 72.4, 71.3, 67.6, 66.6, 51.3, 50.5, 29.4, 29.2, 23.8,
23.5, 20.5, due to the presence of isomers, number of carbons is
more in the spectrum; HRMS (ESI) Calc. for C17H19N3O4
[M+H]+ 343.1407, Found: 343.1404.
o
80 Compound 36: Yield 0.104 g (56 %); Mp 139-141 C; IR (KBr,
cm–1) 3364, 3134, 1567, 1479, 1447, 1288, 1233, 1118, 1052,
958, 745, 690; 1H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H,
triazole-H), 7.73 (d, J ~ 7.6 Hz, 2H, Ar-H), 7.55 (d, J = 8.0 Hz,
1H, Ar-H), 7.39 (t, J ~ 7.6 Hz, 2H, Ar-H), 7.32 (t, J ~ 7.6 Hz, 1H,
85 Ar-H), 7.24-7.28 (m, 1H, Ar-H), 6.87-6.91 (m, 2H, Ar-H), 4.79
(dd, J = 14.0 and 3.6 Hz, 1H, CHaHb), 4.65 (dd, J = 14.0 and 6.4
Hz, 1H, CHaHb), 4.58-4.59 (m, 1H, OCH), 4.02-4.07 (m, 2H,
CH2),3.77 (br, 1H, OH); 13C NMR(400 MHz, CDCl3) δ 154.4,
147.7, 133.5, 130.3, 128.9, 128.8, 128.3, 125.7, 123.0, 121.6,
90 113.9, 112.4, 70.0, 68.8, 53.0; HRMS (ESI) Calc. for
C17H17BrN3O2 [M+H]+ 375.0505 and 376.0663, Found: 375.0508
and 376.0491.
o
Compound 32: Yield 0.125 g (65%); mp 166-169 C; IR (KBr,
cm–1) 3332, 3125, 2918, 2856, 1676, 1614, 1563, 1454, 1324,
1242, 1117, 952, 910, 750; 1H NMR (400 MHz, CDCl3) δ 8.79 (s,
30 1H, OH), 7.93 (s, 1H, triazole-H), 7.85 (d, J = 8.0 Hz, 2H, Ar-H),
7.44-7.48 (m, 3H, Ar-H), 7.31-7.40 (m, 2H, Ar-H), 6.86 (s, 1H,
Ar-H), 6.84 (d, J = 8.4 Hz, 1H, =CH), 6.16-6.23 (m, 1H, =CH),
3.93 (d, J = 6.0 Hz, 2H, CH2), 2.37 and 2.84 (2 s, 6H, 2 CH3); 13
C
NMR (100 MHz, CDCl3) δ 155.5, 148.2, 147.2, 129.8, 129.1,
35 128.8, 128.2, 127.6, 126.0, 121.9, 119.2, 117.3, 116.7, 115.5,
49.5 (NCH2), 34.8, 21.7; HRMS (ESI) Calc. for C19H20N4O3SNa
[M+Na]+ 407.1154, Found: 407.1153. This compound was
General procedure for the synthesis compounds 37-41:
An oven-dried Schlenk tube with a magnetic stirring bar was
95 charged with benzotriazole (0.5 mmol) and epoxide (0.5 mmol)
and then heated at 100 oC for 2 h. Later, CuI (10 mol%), picolinic
acid (20 mol%), cesium carbonate (3.0 equiv.), and toluene (1
mL) were added under nitrogen atmosphere and the contents
heated at 120 oC (oil bath temperature) for 12 h. The mixture was
100 then cooled to ambient temperature, diluted with 2-3 mL of ethyl
acetate, passed through a plug of celite, and then washed with 20-
30 mL of ethyl acetate. The organic layer was evaporated and the
residue purified by column chromatography on silica gel by using
hexane/ethyl acetate (75/25) as eluent to afford the desired
105 product. Compounds 37-40 were synthesised following the molar
quantities mentioned above in each case. Compound 41 was
isolated without addition of copper-catalyst.
o
crystallized from dichloromethane/hexane (2:1) mixture at 25 C.
X-ray structure was determined for this compound.
40 Compound 33: (approx. 1:1 diastereomeric ratio),Yield 0.111 g
(75%); gummy solid; IR (neat, cm–1) 3134, 2942, 2860, 1734,
1
1677, 1468, 1441, 1353, 1260, 1162, 1112, 767, 701; H NMR
(400 MHz, CDCl3) δ 7.94 (s, 1H, triazole-H), 7.83-7.86 (m, 5H,
Ar-H), 7.32-7.45 (m, 6H, Ar-H), 5.20 (m, 2H, =CH), 3.80-4.84
45 (m, 11H), 3.42-3.47 (m, 1H), 1.43-2.08 (m, 12H), due to the
presence of isomers, number of protons is doubled in the
assignment; 13C NMR (100 MHz, CDCl3) δ 149.7, 147.0, 130.6,
128.9, 128.2, 125.8, 121.1, 120.9, 108.8, 107.6, 75.0, 73.3, 72.3,
71.3, 67.6, 66.5, 51.1, 50.2, 29.4, 29.2, 23.8, 23.6, 20.5, due to the
50 presence of isomers, number of carbons is more in the spectrum;
HRMS (ESI) Calc. for C17H20N3O2 [M+H]+ 298.1556, Found:
298.1552.
o
Compound 37: Yield 0.99 g (74 %); Mp 128-130 C; IR (KBr,
cm–1) 1594, 1506, 1451, 1342, 1265, 1194, 1040, 914, 832, 750;
110 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.4Hz, 1H, Ar-H),
7.50-7.59 (m, 2H, Ar-H), 7.38-7.42 (m, 1H, Ar-H), 6.83-6.93 (m,
4H, Ar-H), 4.96 (d, J = 5.6 Hz, 2H, CH2), 4.74-4.78 (m, 1H,
OCH), 4.36 (dd, J ~ 12.0 and 2.4 Hz, 1H, CHaHb), 3.96 (dd, J =
12.0 and 6.0 Hz, 1H, CHaHb); 13C NMR (100 MHz, CDCl3) δ
115 145.9, 142.8, 142.0, 133.8, 127.8, 124.2, 122.1, 120.0, 117.5,
Compound 34: (approx. 1:1 diastereomeric ratio),Yield 0.11 g
(71%); gummysolid; IR (neat, cm–1) 3134, 2942, 2860, 1742,
1
55 1682, 1496, 1447, 1353, 1260, 1167, 1112, 822, 729; H NMR
(400 MHz, CDCl3) δ 7.81 and 7.90 (2 s, 2H, triazole-H), 7.71-
7.75 (m, 4H, Ar-H), 7. 23-7.27 (m, 4H, Ar-H), 5.18-5.19 (m, 2H,
=CH), 3.79-4.82 (m, 11H), 3.41-3.46 (m, 1H), 2.38 (s, 6H), 1.53-
This journal is © The Royal Society of Chemistry [year]
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Organic & Biomolecular Chemistry
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DOI: 10.1039/C3OB41332B
117.4, 109.9, 71.9, 65.0, 48.1; HRMS (ESI) Calc. for C15H14N3O2
[M+H]+ 268.1087, Found: 268.1088.
were refined anisotropically; hydrogen atoms were fixed by
geometry or located by a Difference Fourier map and refined
o
Compound 38: Yield 0.124 g (77 %); Mp 115-116 C; IR (KBr, 60 isotropically.
cm–1) 2953, 2871, 1595, 1452, 1321, 1266, 1058, 915, 822, 745;
Crystal data
5
1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.4 Hz, 1H, Ar-H),
16: C17H14ClN3O2, M = 327.76, Monoclinic, Space group
7.48-7.54 (m, 2H, Ar-H), 7.38-7.42 (m, 1H, Ar-H), 6.91 (dd, J ~
8.4 and 2.4 Hz, 1H, Ar-H), 6.84-6.86 (m, 2H, Ar-H), 4.95 (d, J =
6.0 Hz, 2H, CH2), 4.73-4.78 (m, 1H, OCH), 4.33 (dd, J ~ 11.6
and 2.4 Hz, 1H, CHaHb), 3.98 (dd, J = 11.6 and 5.6 Hz, 1H,
P2(1)/c, a = 11.1770(11), b = 5.4737(4), c = 25.780(3) Å, β =
65 100.299(9)o, V = 1551.8(3) Å3, Z = 4, ꢀ = 0.259 mm-1,
data/restraints/parameters: 2742 / 0 / 208, R indices (I > 2σ(I)):
R1 = 0.0599, wR2 (all data) = 0.1575. CCDC No. 929370.
20: C24H26N4O3S, M = 450.55, Monoclinic, Space group P2(1)/n,
a = 8.5356(5), b = 10.9149(6), c = 24.3049(16) Å, β =
70 95.720(6)o, V = 2253.1(2) Å3, Z = 4, ꢀ = 0.178 mm-1,
data/restraints/parameters: 3948 / 0 / 290, R indices (I > 2σ(I)):
R1 = 0.0699, wR2 (all data) = 0.1956. CCDC No. 929371.
30: C18H16N4O4, M = 352.35, Triclinic, Space group P-1, a =
6.0255(6), b = 10.3665(11), c = 12.6263(14) Å, α = 92.903(9)o, β
75 = 97.168(8)o, γ = 94.666(8)o, V = 840.11(15) Å3, Z = 2, ꢀ = 0.101
mm-1, data/restraints/parameters: 2948/ 0/235, R indices (I >
2σ(I)): R1 = 0.0549, wR2 (all data) = 0.1525. CCDC No. 929372.
32: C19H20N4O3S, M = 384.45, Monoclinic, Space group P2(1)/c,
a = 8.4958(6), b = 11.6503(8), c = 18.9628(14) Å, β =
80 94.116(1)o, V = 1872.1(2) Å3, Z = 4, ꢀ = 0.201 mm-1,
data/restraints/parameters: 3694 / 0 / 247, R indices (I > 2σ(I)):
R1 = 0.0419, wR2 (all data) = 0.1269. CCDC No. 929373.
10 CHaHb), 1.28 (s, 9H, C(CH3)3); 13C NMR (100 MHz, CDCl3) δ
146.0, 145.6, 141.3, 142.4, 133.9, 127.8, 124.2, 120.1, 119.0,
116.8, 114.7, 109.9, 72.0, 65.1, 48.0, 34.3, 31.5; HRMS (ESI)
Calc. for C19H22N3O2 [M+H]+ 324.1713, Found: 324.1711.
o
Compound 39: Yield 0.108 g (73 %); Mp 119-121 C; IR (KBr,
15 cm–1) 2921, 1605, 1496, 1447, 1321, 1211, 1151, 1118, 1063,
904, 833, 751; 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 8.4 Hz,
1H, Ar-H), 7.59 (d, J = 8.4 Hz, 1H, Ar-H), 7.52 (t, J = 7.6 Hz,
1H, Ar-H), 7.40 (t, J = 7.6 Hz, 1H, Ar-H), 6.56 (s, 1H, Ar-H),
6.50 (s, 1H, Ar-H), 4.94 (d, J = 5.6 Hz, 2H, CH2), 4.70-4.72 (m,
20 1H, OCH), 4.34 (dd, J = 11.6 and 2.0 Hz, 1H, CHaHb), 3.94 (dd, J
= 11.6 and 6.0 Hz, 1H, CHaHb), 2.17 and 2.21 (2 s, 6H, 2 CH3);
13C NMR (100 MHz, CDCl3) δ 146.0, 141.5, 138.8, 133.9, 130.9,
127.8, 126.7, 124.2, 124.1, 120.0, 115.4, 110.0, 71.9, 65.1, 48.2,
20.7, 15.4, HRMS (ESI) Calc. for C17H18N3O2 [M+H]+ 296.1400,
25 Found: 296.1404.
o
Compound 40: Yield 0.170 g (81 %); Mp 142-144 C; IR (KBr,
Acknowledgment
cm–1) 3047, 2915, 1595, 1490, 1447, 1348, 1255, 1162, 1068,
915, 849, 750; 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.0 Hz,
1H, Ar-H), 7.78 (d, J = 8.0 Hz, 1H, Ar-H), 7.51-7.53 (m, 2H, Ar-
30 H), 7.38-7.43 (m, 3H, Ar-H), 7.03-7.10 (m, 3H, Ar-H), 6.94 (t, J
= 7.6 Hz, 1H, Ar-H), 6.77 (d, J = 8.4 Hz, 1H, Ar-H), 4.80 (d, J =
4.8 Hz, 2H, CH2), 4.36 (dd, J ~ 14.4 and 2.0 Hz, 1H, CHaHb),
3.76-3.78 (m, 1H, OCH), 3.17 (dd, J = 14.4 and 10.0 Hz, 1H,
CHaHb), 2.32 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ 146.0,
35 144.6, 135.2, 133.7, 130.1, 127.8, 127.1, 126.4, 124.8, 124.3,
123.4, 121.6, 120.2, 117.4, 109.8, 70.5, 49.5, 46.2, 21.6; HRMS
(ESI) Calc. for C22H21N3O2S [M+H]+ 421.1335, Found:
421.1334.
We thank Department of Science and Technology (DST, New
85 Delhi) for financial support and Single Crystal X-ray
diffractometer facility, and the University Grants Commission
(UGC, New Delhi) for equipment under UPE and CAS programs.
MNR thank Council of Scientific and Industrial Research (CSIR,
New Delhi) for fellowship. KCK thanks DST for the J. C. Bose
90 fellowship.
Notes and references
a School of Chemistry, University of Hyderabad, Hyderabad 500 046, A.
P., India. Fax: (+91)-40-23012460; Tel: (+91)-40-231348560; E-mail:
kckssc@uohyd.ernet.in, kckssc@yahoo.com
o
Compound 41: Yield 0.182 g (92 %); Mp 138-140 C; IR (KBr,
95 † Electronic Supplementary Information (ESI) available [details on the
40 cm–1) 3238, 1584, 1474, 1463, 1441, 1278, 1249, 1118, 1058,
1
synthesis of precursors 1a-1k and 2a-2k, H and 13C NMR spectra, and
1
CIF files. See DOI: 10.1039/b000000x/
751; H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.4 Hz, 1H, Ar-
H), 7.78 (d, J = 7.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.4 Hz, 1H, Ar-
H), 7.46 (t, J ~ 7.6 Hz, 1H, Ar-H), 7.29-7.33 (m, 2H, Ar-H), 6.74-
6.80 (m, 2H, Ar-H), 5.03 (dd, J ~ 12.0 and 4.0 Hz, 1H, CHaHb),
45 4.92 (dd, J ~ 14.4 and 6.8 Hz, 1H, CHaHb), 4.67-4.68 (m, 1H,
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