Microwave-Assisted Copper-Catalyzed Four-Component Tandem Synthesis of 3- N -Sulfonylamidine Coumarins

Article abstract of DOI:10.1021/acs.joc.5b00738

Microwave-assisted copper-catalyzed four-component tandem synthesis of 3-N-sulfonylamidine coumarins has been accomplished by the coupling of salicylaldehydes, propiolates, sulfonyl azides, and secondary amines. This one-pot protocol affords an effective route for the construction of functionalized coumarin structural frameworks in a single operation with moderate to high yields.

Full text of DOI:10.1021/acs.joc.5b00738

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Article
Microwave-Assisted Copper-Catalyzed Four Component
Tandem Synthesis of 3-N-Sulfonylamidine Coumarins
Govindarasu Murugavel, and Tharmalingam Punniyamurthy
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00738 • Publication Date (Web): 29 May 2015
Downloaded from http://pubs.acs.org on May 31, 2015
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Microwave-Assisted Copper-Catalyzed Four Component Tandem Synthesis
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of 3-N-Sulfonylamidine Coumarins
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Govindarasu Murugavel and Tharmalingam Punniyamurthy*
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Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati-781039, India
e-Mail: tpunni@iitg.ernet.in
ABSTRACT: Microwave-assisted copper-catalyzed four-component tandem synthesis of 3-N-
sulfonylamidine coumarins has been described by the coupling of salicylaldehydes, propiolates,
sulfonyl azides and secondary amines. This one-pot protocol affords an effective route for the
construction of functionalized coumarin structural frameworks in single operation with moderate
to high yields.
INTRODUCTION
Coumarins are an important class of heterocyclic scaffolds that exist widely in nature1 with
numerous interesting biological and medicinal properties (Figure 1).2 Moreover, coumarins serve
as an excellent fluorescent probes in biology and medicine,3 as well as dyes in laser technology.4
Classically, coumarin core structure is constructed via Knoevenagel condensation (Scheme 1a).
However, this traditional approach often suffers due to limited substrate scope and troublesome
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chemical processes.5 Development of effective methods for the construction of functionalized
coumarin structural frameworks is thus important in organic synthesis (Scheme 1b).6
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Multicomponent one-pot tandem reaction affords a powerful tool for the conversion of
simple substrates into the diverse complex molecules in a single operation.7 Furthermore,
microwave organic synthesis provides the advantages of greater reactivity, mild reaction
conditions and high selectivity.8 Recently, click chemistry has been considerably explored for the
formation of ketenimine and subsequent reaction with nucleophiles for the construction of
diverse structural scaffolds.9 In continuation of our studies on ketenimine reactions,9q we here
report an efficient microwave-assisted copper(I)-catalyzed four-component synthesis of 3-N-
sulfonylamidine coumarins by the coupling of salicylaldehydes, propiolates, sulfonyl azides and
secondary amines (Scheme 1c). This protocol is selective and affords a potential route for the
construction of functionalized 3-N-sulfonylamidine coumarins in moderate to high yields.10
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N
O
O
O
O
O
N
O
MeO
O
OH
N
H
O
OH
O
O
OH
NH2
O
O
Novobiocin
Ensaculin KA-672
Me
O
NH
OH
O
O
N
N
O
O
O
O
N
O
O
O
O
O
Acenocoumarol
Carbocromen
Batoprazine
Figure 1. Some examples of biologically important coumarin derivatives
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Scheme 1. Methods for Coumarin Syntheses
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RESULTS AND DISCUSSION
Initially, optimization of the reaction was carried out employing salicylaldehyde 1a, ethyl
propiolate 2a, tosyl azide 3a and diisopropylamine 4a as the model substrates using a series of
copper salts in the presence of different bases (Table 1). The coupling of ethyl propiolate 2a,
tosyl azide 3a and diisopropylamine 4a readily took place to afford amidine10a 5 as the sole
product, and the aldehyde 1a failed to react when the substrates were stirred with 10 mol % CuI
and 1.2 equiv K3PO4 for 0.5 h in 1,4-dioxane at room temperature (entry 1). However, increasing
the reaction temperature to reflux for 24 h led to the coupling of all the substrates to afford ester
6 and coumarin 7a in 19% and 30%, respectively, along with amidine 5 in 48% (entry 2).
Subsequent screening of the base led to an increase in the formation of 7a to 50% using K2CO3,
while Cs2CO3 exhibited inferior results (entries 3-4). In contrast, Na2CO3, and the organic bases
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Table 1. Optimization of the Reaction Conditionsa
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yield (%)b
entry
[Cu]
CuI
CuI
CuI
CuI
CuI
base
solvent
5
6
7a
n.d.c
1
2
3
4
5
K3PO4
K3PO4
K2CO3
Cs2CO3
Na2CO3
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
<99
n.d.
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14
39
17
48
34
38
83
30
50
16
n.d.
6
7
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9
CuI
CuI
Et3N/lutidine
DBU
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
DMSO
<99
75
44
30
60
71
50
64
n.d.
25
12
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25
n.d.
8
n.d.
n.d.
37
CuBr
CuCl
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
39
10 Cu(acac)2
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12
13
CuI
CuI
CuI
23
toluene
36
DMF
19
n.d.
a
Aldehyde 1a (0.5 mmol), ethyl propiolate 2 (0.5 mmol), tosyl azide 3a (0.6 mmol), amine 4
b
(0.6 mmol), Cu source (10 mol %), base (0.6 mmol), solvent (1 mL), 0.5 h, rt; reflux, 24 h.
Determined by 400 MHz 1H NMR. c0.5 h, rt. n.d.= not detected.
such as DBU, Et3N and 2,6-lutidine failed to produce the target heterocycle 7a (entries 5-7). In a
set of copper sources screened, CuI, CuCl, CuBr and Cu(acac)2, the former gave the best results
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(entries 8-10). Dioxane was found to be the solvent of choice, while the reactions using DMSO,
toluene and DMF gave inferior results (entries 11-13). Recrystallization of 6 in MeOH gave
single crystal whose structure was confirmed by X-ray analysis (see the Supporting Information).
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Next, the reaction was examined using microwave-heating and the results are summarized in
table 2. These reactions exhibited greater reactivity and selectivity compared to the conventional
heating reactions described in table 1. The best results observed at 130 °C [150 W, closed vial] to
afford the target heterocycle 7a in 1 h with up to 88% along with 7% of 6. Further increase of the
o
reaction temperature to 140 C led to drop in yield to 81% due to decomposition of the product
7a. Likewise, lowering the catalyst loading (5 mol%) or the reaction temperature (120 °C) or
increasing the quantity of the base (2 equiv) led to drop in yield to <70%. A control experiment
confirmed that without the copper source the coupling reaction was not observed. Furthermore,
the reaction in sealed tube without microwave irradiation afforded 7a in 34 % yield (entry 7).
Having the optimized reaction conditions, the substrate scope was explored with a series of
substituted salicylaldehydes (Scheme 2). The aldehydes 1b-d having substitution at the 3-
position with chloro, methoxy and tert-butyl groups underwent reaction to provide the coumarin
derivatives 7b-d in 60-83% yields. The reaction of the aldehydes 1e-g bearing alkoxy groups at
the 4-position furnished 7e-g in 25-67% yields. Likewise, the aldehydes 1h-j and 1l-n having
bromo, chloro, fluoro, methoxy and methyl substituents at the 5-position readily reacted to give
the coumarin derivatives 7h-j and 7l-n in 65-78% yields, while the reaction of the aldehydes 1k
and 1o with strong electron withdrawing groups 5-CHO and 5-NO2 was less-successful.
Furthermore, the sterically hindered disubstituted aldehydes 1p-q with 5-iodo-3-tert- butyl and
3,5-di-tert-butyl groups underwent reaction to produce the heterocycles 7p-q in 76-80% yields.
In addition, 2- naphthaldehyde reacted to furnish 7r in good yield, which on recrystallization in
MeOH-CH2Cl2 (1:1) gave single crystals whose structure was confirmed by X-ray analysis (see
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the Supporting Information). These results suggest that the reactions can tolerate substantial
steric hindrance, and the aldehydes with electron donating groups exhibit superior results
compared to that having electron withdrawing groups.
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Table 2. Effect of Microwave Heatinga
yield (%)b
entry
T (°C)
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7a
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130
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n.d
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72d
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n.d.
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63d
34e
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a
Aldehyde 1a (0.5 mmol), ethyl propiolate 2 (0.5 mmol), tosyl azide 3a (0.6 mmol), amine 4a
(0.6 mmol), CuI (10 mol %), K2CO3 (0.6 mmol), 1,4-dioxane (1 mL), 0.5 h, rt; MW, 130 oC,1 h.
b Determined by 400 MHz 1H NMR. c 5 mol % CuI. d 2 equiv K2CO3. e Sealed tube without MW,
1 h. n.d.= not detected.
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Scheme 2. Reaction of Various Substituted Salicylaldehydesa
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aAldehyde 1 (0.5 mmol), 2 (0.5 mmol), 3a (0.6 mmol), 4a (0.6 mmol), CuI (10 mol %), K2CO3
3
4
5
6
b
(0.6 mmol), 1,4-dioxane (1 mL), rt, 0.5 h, air; MW, 130 °C, 1 h. Ester (~5%) was obtained as
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byproduct. n.d. = not detected.
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Scheme 3. Reaction of Various Sulfonyl Azidesa
aAldehyde 1a (0.5 mmol), 2a (0.5 mmol), 3b-f (0.6 mmol), 4a (0.6 mmol), CuI (10 mol %),
K2CO3 (1.2 equiv), 1,4-dioxane (1 mL), rt, 0.5 h, air; MW, 130 °C, 1 h.
The utility of the protocol was extended to the reaction of various sulfonyl azides (Scheme
3). Methanesufonyl azide 3b underwent reaction to furnish the coumarin derivative 7s in 72%
yield. The reaction of phenyl sulfonyl azide 3c occurred to produce 7t in 80% yield. Likewise,
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phenyl sulfonyl azides 3d-f having 4-chloro, 4-methoxy and 2,4,6-trimethyl groups underwent
reaction to afford the corresponding coumarin derivatives 7u-w in 68-82% yields. These results
suggest that the reaction can be compatible with aliphatic as well as aromatic sulfonyl azides
with good yields.
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Scheme 4. Reactions with Different Propiolates
Scheme 5. Reactions with Different Amines
Next, the reactions of different propiolates were examined (Scheme 4). Benzyl propiolate 2b
proceeded reaction with 22% yield, while the reaction of p-tolyl propiolate 2c produced the
target heterocycle 7a in 14% yield. Finally, the reaction of different amines was investigated
(Scheme 5). The reactions of cyclohexylamine and morpholine failed to produce the coupled
products due to decomposition. However, benzyl cyclohexylamine 4b underwent reaction to give
7x as a 3:1 mixture of isomers in 9% yield. Likewise, the reaction of isopropyl cyclohexylamine
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4c gave 7y as a 1:1 mixture of isomers in a 9% yield. These results suggest that the nature of
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propiolate and secondary amine plays a crucial role in the coupling reaction.
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Scheme 6. Mechanistic Studies
Scheme 7. Proposed Catalytic Cycle
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To gain insight into the catalytic pathway, the reaction of 1a, 2, 3a and 4a was stopped at 10
min and the resulting mixture was analyzed using ESI mass analysis, and found three major
species 5, 6 and 7a (see the Supporting Information). Furthermore, the substrates 2, 3a and 4a
readily underwent coupling to provide 5 that could be readily reacted with the aldehyde 1a to
furnish 7a in 78% yield (Scheme 6a). In addition, the ester 6 readily underwent cyclization to
furnish 7a in 85% yield (Scheme 6b). These results suggest that the reaction may take place via
the intermediates 5 and 6 to yield the target heterocycle 7a. Thus, the cycloaddition of 2 with 3
may produce ketenimine9 B via A. Nucleophilic addition of the amine to the intermediate B may
furnish 5 that can react with the aldehyde 1 to give C, which may cyclize to produce 7 by trans-
esterification (Scheme 7).
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In conclusion, copper(I)-catalyzed four-component tandem synthesis of 3-N-sulfonylamidine
coumarin has been developed via the coupling of salicylaldehydes, propiolates, sulfonyl azides
and secondary amines. The reaction using microwave irradiation is found to be superior to the
conventional heating processes. The greater reactivity, mild condition and high selectivity
constitute the significant practical advantages. This study may open new avenue for the further
development of multcomponent studies for the synthesis of highly functionalized coumarin
derivatives.
EXPERIMENTAL SECTION
General Information. The reaction was performed in closed vial using CEM Discover LabMate
microwave reactor equipped with surface sensor for temperature measurement. NMR spectra
were recorded on 400 and 600 MHz spectrometers using CDCl3 as a solvent and the data are
accounted as follows: chemical shifts (δ ppm) (multiplicity, coupling constant (Hz), integration).
The abbreviations for multiplicity are as follows: s = singlet, d = doublet, t = triplet, m =
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multiplet and dd = doublet of doublets. Infrared spectra were recorded on FT-IR spectrometer.
Melting points were determined with melting point apparatus and are uncorrected. HRMS mass
spectra were analyzed using Q-TOF instrument. For single crystal X-ray analysis, the intensity
data were collected using CCD diffractometer, equipped with 1.75 kW sealed-tube Mo-Kα
irradiation (λ= 0.71073 Å) at 298(2) K and the structures were solved by direct methods using
SHELXL-97 (Göttingen, Germany) and refined with full-matrix least squares on F2 using
SHELXL-97. CuI (98%) of Aldrich, CuBr (97%) of Alfa Aesar and CuCl (98%) of Rankem
were used as received. 2,6-Lutidine (98%), ethyl propiolate (99%), Cs2CO3 (99%), K3PO4 (98%),
Na2CO3 (99%) and DBU (98%) were purchased from commercial suppliers and used as received.
Solvents were purchased from commercial source and purified prior to use.11 Substituted
salicylaldehydes12,13 and sulfonyl azides14 were prepared according to the literature procedures.
The reactions were monitored by analytical TLC on silica gel G/GF 254 plate and the column
chromatography was performed with 60-120 mesh silica gel.
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Benzyl propiolate 2b.15 Analytical TLC on silica gel, 1:19 ethyl acetate-hexane Rf = 0.50;
1
colorless liquid; yield 70% (561 mg); H NMR (400 MHz, CDCl3) δ 7.40-7.37 (m, 5H), 5.23 (s,
13
2H),2.90 (s, 1H); C{1H} NMR (100 MHz, CDCl3) δ 152.8, 134.7, 128.93, 128.9, 128.8, 75.3,
74.7, 68.1; FT-IR (neat) 2961, 2924, 2855, 2120, 1716, 1605, 1383, 1223, 1020, 749, 696, 668,
562 cm-1.
p-Tolyl propiolate 2c.16 Analytical TLC on silica gel, 1:19 ethyl acetate-hexane Rf = 0.30;
1
colorless liquid; yield 53% (424 mg); H NMR (400 MHz, CDCl3) δ 7.20 (d, J = 8.4 Hz, 2H),
13
7.03 (d, J = 8.4 Hz, 2H), 3.06 (s, 1H), 2.35 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 151.4,
147.8, 136.6, 130.3, 121.1, 76.8, 74.5, 21.1; FT-IR (neat) 2962, 2924, 2855, 2125, 1731, 1504,
1384, 1217, 1197, 1018, 909, 807, 744, 607, 502 cm-1.
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General Procedure for the Synthesis of Coumarins. To a stirred solution of propiolate 2 (0.5
mmol), sulfonyl azide 3 (0.6 mmol) and CuI (0.05 mmol, 9.5 mg) in 1,4-dioxane (1 mL) was
added secondary amine 4 (0.5 mmol), salicylaldehyde 1 (0.5 mmol) and K2CO3 (0.6 mmol, 82.9
mg) at room temperature under air. After 0.5 h (arrested N2 bubbles), the reaction vial was sealed
with a cap and stirred at 130 °C [150 W] for 1 h using microwave-irradiation. The solvent was
then evaporated under vacuo and the residue was diluted with CH2Cl2 (30 mL), and washed with
saturated NH4Cl (10 mL) and water (10 mL). Drying (Na2SO4) and evaporation of the solvent
gave a residue that was purified on silica gel column chromatography using n-hexane/ethyl
acetate as eluent.
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Compound 5.10a Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.40; colorless solid;
mp 122-123 °C. 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 7.6 Hz, 2H),
4.16-4.11 (m, 4H), 3.95-3.88 (m, 1H), 3.61 (br. s, 1H), 2.38 (s, 3H), 1.38 (d, J = 6.8 Hz, 6H),
1.27-1.21 (m, 9H); 13C {1H}NMR (100 MHz, CDCl3) δ 166.9, 157.9, 141.7, 141.1, 129.0, 126.2,
61.7, 48.4, 37.6, 21.4, 20.2, 19.9, 14.0; FT-IR (KBr) 3015, 2983, 2936, 2907, 1729, 1547, 1484,
1441, 1369, 1325, 1276, 1201, 1135, 1083, 1055, 960, 885, 810, 763, 715, 663, 551, 542 cm-1;
HRMS (ESI) m/z calcd for C18H29N2O4S [M+H]+: 369.1848, found: 369.1875.
Compound 6. Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.32; colorless solid;
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mp 206-207 °C. H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 7.87 (s, 1H), 7.72 (d, J = 8.4 Hz,
2H), 7.43 (dd, J = 8.4, 1.6 Hz, 1H), 7.11-7.06 (m, 3H), 6.86 (d, J = 7.6 Hz, 1H), 6.62 (t, J = 8.0
Hz, 1H), 4.30-4.22 (m, 2H), 4.09-4.01 (m, 1H), 3.63-3.55 (m, 1H), 2.28 (s, 3H), 1.57 (d, J = 6.8
Hz, 3H), 1.49 (d, J = 6.8 Hz, 3H), 1.30 (t, J = 7.2 Hz, 3H), 1.11 (d, J = 6.4 Hz, 3H), 0.74 (d, J =
6.8 Hz, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ 165.0, 160.9, 156.8, 141.8, 40.5, 136.7, 132.5,
129.0, 129.0, 126.6, 122.9, 119.8, 119.6, 116.7, 61.7, 52.4, 48.4, 21.5, 20.2, 19.7, 19.0, 14.2; FT-
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IR (KBr) 3390, 2973, 2924, 2853, 1717, 1700, 1618, 1606, 1536, 1463, 1443, 1367, 1279, 1253,
1219, 1142, 1084, 1036, 1017, 906, 813, 776, 760, 675, 596, 554 cm-1; HRMS (ESI) m/z calcd
for C25H33N2O5S [M+H]+: 473.2110, found: 473.2117.
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(Z)-N,N-Diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide 7a. Analytical TLC
on silica gel, 2:3 ethyl acetate-hexane Rf = 0.40; colorless solid; yield 75% (160 mg); mp 257-
258 °C; 1H NMR (600 MHz, CDCl3) δ 7.72 (s, 1H, H-4), 7.65 (d, J =7.8 Hz, 2H, Ar-H (tosyl)),
7.58 (t, J = 7.8 Hz, 1H, H-7), 7.54 (d, J = 7.8 Hz, 1H, H-5), 7.34-7.30 (m, 2H, H-6 and H-8),
7.16 (d, J = 7.8 Hz, 2H, Ar-H (tosyl)), 3.89-3.85 (m, 1H, -N-CH-), 3.70-3.66 (m, 1H, -N-CH-),
2.36 (s, 3H, -CH3 (tosyl)), 1.58 (d, J = 6.6 Hz, 3H, -CH3 (isopropyl)), 1.42 (d, J =7.2 Hz, 3H, -
CH3 (isopropyl)), 1.26 (d, J = 6.6 Hz, 3H, -CH3 (isopropyl)), 1.14 (d, J = 6.6 Hz, 3H, -CH3
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(isopropyl)); C {1H}NMR (150 MHz, CDCl3) δ 157.5 (C), 157.4 (C), 154.2 (C), 142.1 (C),
141.6 (CH), 140.8 (C), 132.9 (CH), 129.2 (CH), 129.0 (CH), 126.5 (CH), 125.1 (CH), 123.3 (C),
118.2 (C), 117.1 (CH), 52.8 (CH), 48.6 (CH), 21.6 (CH3), 20.7 (CH3), 20.2 (CH3), 20.1 (CH3),
19.7 (CH3); FT-IR (KBr) 3035, 2969, 2932, 1717, 1628, 1608, 1547, 1445, 1371, 1279, 1251,
1210, 1142, 1087, 1013, 901, 812, 780, 759, 676, 595, 553 cm-1; HRMS (ESI) m/z calcd for
C23H27N2O4S [M+H]+: 427.1692, found: 427.1692.
(Z)-8-Chloro-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7b.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.37; colorless solid; 60% (138 mg);
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mp 285-286 °C; H NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 7.66-7.62 (m, 3H), 7.48 (d, J = 7.6
Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.17 (d, J = 7.6 Hz, 2H), 3.86-3.81 (m, 1H), 3.72-3.66 (m,
1H), 2.38 (s, 3H), 1.60 (d, J = 6.8 Hz, 3H), 1.43 (d, J = 7.2 Hz, 3H), 1.27 (d, J = 6.4 Hz, 3H),
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1.16 (d, J = 6.4 Hz, 3H); C {1H}NMR (100 MHz, CDCl3) δ 156.8, 156.3, 149.9, 142.3, 141.2,
140.6, 133.2, 129.2, 127.5, 126.6, 125.2, 124.0, 122.1, 119.5, 52.9, 48.7, 21.6, 20.7, 20.2, 20.1,
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19.7; FT-IR (KBr) 3079, 2998, 2973, 2927, 1727, 1623, 1600, 1547, 1476, 1442, 1367, 1270,
1208, 1138, 1087, 1055, 1014, 903, 838, 787, 756, 682, 593, 551 cm-1; HRMS (APCI) m/z calcd
for C23H26ClN2O4S [M+H]+: 461.1302, found: 461.1301.
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(Z)-N,N-Diisopropyl-8-methoxy-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7c.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.50; colorless solid; yield 68% (155
mg); mp 294-295 °C; 1H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.66 (d, J = 8.0 Hz, 2H), 7.26
(d, J = 10.0 Hz, 1H), 7.17-7.11 (m, 4H), 3.97 (s, 3H), 3.88-3.84 (m, 1H), 3.69-3.65 (m, 1H), 2.37
(s, 3H), 1.59 (d, J = 6.8 Hz, 3H), 1.41 (d, J = 6.8 Hz, 3H), 1.25 (d, J = 6.8 Hz, 3H), 1.14 (d, J =
6.8 Hz, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ 157.3, 156.9, 147.4, 143.9, 142.0, 141.7, 140.8,
129.1, 126.6, 124.9, 123.5, 120.3, 118.8, 114.8, 56.5, 52.7, 48.5, 21.6, 20.6, 20.2, 20.1, 19.7; FT-
IR (KBr) 3080, 3032, 2995, 2967, 2936, 2844, 1723, 1623, 1610, 1578, 1543, 1489, 1453, 1369,
1267, 1213, 1175, 1135, 1104, 1085, 1059, 1016, 975, 950, 904, 839, 809, 787, 752, 677, 595,
551 cm-1; HRMS (APCI) m/z calcd for C24H29N2O5S [M+H]+: 457.1797, found: 457.1797.
(Z)-8-(tert-Butyl)-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7d.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.53; colorless solid; yield 83% (200
mg); mp 249-250 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (s, 1H), 7.59 (d, J = 8.0 Hz, 3H), 7.42
(d, J = 7.6 Hz, 1H), 7.26 (t, J = 8.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 3.87-3.84 (m, 1H), 3.71-
3.68 (m, 1H), 2.33 (s, 3H), 1.61 (d, J = 7.2 Hz, 3H), 1.48 (s, 12H), 1.27 (d, J = 6.0 Hz, 3H), 1.15
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(d, J = 6.4 Hz, 3H); C {1H}NMR (100 MHz, CDCl3) δ 157.7, 156.6, 152.8, 143.2, 141.9,
140.7, 138.1, 130.6, 129.1, 127.5, 126.5, 124.6, 121.4, 118.4, 52.7, 48.5, 35.1, 30.0, 21.5, 20.6,
20.2, 20.0, 19.6; FT-IR (KBr) 2996, 2973, 2936, 2881, 1727, 1626, 1593, 1542, 1449, 1432,
1370, 1278, 1213, 1172, 1142, 1122, 1085, 1059, 1016, 941, 909, 819, 801, 754, 678, 592, 549
cm-1; HRMS (APCI) m/z calcd for C27H35N2O4S [M+H]+: 483.2318, found: 483.2318.
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(Z)-7-(Benzyloxy)-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7e.
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Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.30; yellow solid; yield 49% (131
mg); mp 222-223 °C. 1H NMR (600 MHz, CDCl3) δ 7.66 (s, 1H), 7.64 (d, J = 7.8 Hz, 2H), 7.42-
7.41 (m, 5H), 7.36 (d, J = 6.0 Hz, 1H), 7.14 (d, J = 7.2 Hz, 2H), 6.96 (d, J = 7.8 Hz, 1H), 6.86 (s,
1H), 5.15 (s, 2H), 3.89-3.87 (m, 1H), 3.66 (s, 1H), 2.35 (s, 3H), 1.58 (d, J = 6.6 Hz, 3H), 1.43 (d,
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J = 6.0 Hz, 3H), 1.25 (d, J = 6.0 Hz, 3H), 1.13 (d, J = 6.0 Hz, 3H); C{1H} NMR (150 MHz,
CDCl3) δ 162.8, 157.9, 157.7, 156.1, 142.0, 141.9, 140.9, 137.8, 130.1, 129.1, 129.0, 128.6,
127.6, 126.5, 119.4, 114.0, 112.0, 102.1, 70.8, 52.7, 48.5, 21.7, 20.7, 20.2, 20.1, 19.7; FT-IR
(KBr) 2967, 2923, 2856, 1729, 1616, 1538, 1451, 1373, 1267, 1243, 1122, 1082, 808, 754, 679,
619, 550 cm-1; HRMS (ESI) m/z calcd for C30H33N2O5S [M+H]: 533.2105, found: 533.2112.
(Z)-N,N-Diisopropyl-7-methoxy-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7f.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.58; colorless solid; yield 67% (153
mg); mp 265-266 °C; 1H NMR (400 MHz, CDCl3) δ 7.67 (s, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.45
(d, J = 8.4 Hz, 1H), 7.17 (d, J = 7.6 Hz, 2H), 6.90 (dd, J = 8.8, 1.2 Hz, 1H), 6.81 (s, 1H), 3.91-
3.86 (m, 4H), 3.70-3.64 (m, 1H), 2.37 (s, 3H), 1.58 (d, J = 6.8 Hz, 3H), 1.43 (d, J = 6.8 Hz, 3H),
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1.26 (d, J = 6.8 Hz, 3H), 1.14 (d, J = 6.8 Hz, 3H); C {1H}NMR (150 MHz, CDCl3) δ 163.8,
157.9, 157.7, 156.2, 141.95, 141.91, 140.9, 130.0, 129.1, 126.5, 119.4, 113.3, 111.8, 101.0, 56.1,
52.7, 48.5, 21.6, 20.7, 20.2, 20.1, 19.7; FT-IR (KBr) 3093, 3052, 2972, 2934, 2849, 1730, 1614,
1540, 1512, 1473, 1459, 1444, 1371, 1271, 1244, 1202, 1125, 1080, 1057, 1024, 972, 901, 854.
807, 763, 726, 675, 593, 550 cm-1; HRMS (APCI) m/z calcd for C24H29N2O5S [M+H]+:
457.1797, found; 457.1798.
(Z)-N,N-Diisopropyl-7-(octyloxy)-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7g.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.32; pale yellow solid; yield 25% (69
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mg); mp 198-199 °C. 1H NMR (600 MHz, CDCl3) δ 7.66 (s, 1H), 7.65 (d, J = 7.8 Hz, 2H), 7.43
(d, J = 8.4 Hz, 1H), 7.17 (d, J = 7.8 Hz, 2H), 6.88 (dd, J = 9.0, 1.8 Hz, 1H), 6.79 (s, 1H), 4.03 (t,
J = 6.6 Hz, 2H), 3.91-3.89 (m, 1H), 3.68-3.66 (m, 1H), 2.37 (s, 3H), 1.84-1.80 (m, 2H), 1.58 (d,
J = 6.6 Hz, 3H), 1.49-1.44 (m, 2H), 1.43 (d, J = 7.2 Hz, 3H), 1.37-1.29 (m, 8H), 1.26 (d, J = 6.6
Hz, 3H), 1.14 (d, J = 6.6 Hz, 3H), 0.90 (t, J = 6.6 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ
163.4, 158.0, 157.8, 156.2, 142.0, 141.9, 141.0, 130.0, 129.1, 126.6, 119.1, 113.7, 111.6, 101.5,
69.0, 52.7, 48.5, 32.0, 29.5, 29.4, 29.1, 26.1, 22.8, 21.6, 20.7, 20.2, 20.1, 19.7, 14.3; FT-IR (KBr)
2967, 2922, 2855, 1728, 1619, 1539, 1373, 1294, 1272, 1251, 1138, 1081, 806, 789, 682, 552
cm-1; HRMS (ESI) m/z calcd for C30H33N2O5S [M+H]: 555.2887, found: 555.2895.
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(Z)-6-Bromo-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7h.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.70; yellow solid; yield 65% (164
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mg); mp 308-309 °C; H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 6.4 Hz, 5H), 7.25 (d, J = 8.8
Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H), 3.85-3.82 (m, 1H), 3.70-3.66 (m, 1H), 2.38 (s, 3H), 1.57 (d, J
= 6.4 Hz, 3H), 1.41 (d, J = 6.4 Hz, 3H), 1.27 (d, J = 6.4 Hz, 3H), 1.15 (d, J = 6.4 Hz, 3H); 13C
{1H}NMR (100 MHz, CDCl3) δ 156.9, 156.8, 153.0, 142.1, 140.7, 140.0, 135.5, 131.2, 129.2,
126.5, 124.6, 119.7, 118.8, 117.6, 52.9, 48.6, 21.6, 20.6, 20.1, 19.7; FT-IR (KBr) 3110, 3045,
2980, 2966, 2925, 1726, 1623, 1602, 1542, 1471, 1448, 1372, 1271, 1241, 1207, 1136, 1083,
1016, 941, 904, 828, 809, 761, 683, 621, 549 cm-1; HRMS (ESI) m/z calcd for C23H26BrN2O4S
[M+H]+: 505.0797, found: 505.0800.
(Z)-6-Chloro-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7i.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.58; yellow solid; yield 68% (156
mg); mp 314-315 °C; 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 6.0 Hz, 3H), 7.52 (s, 2H), 7.31
(d, J = 9.6 Hz, 1H), 7.19 (d, J = 7.6 Hz, 2H), 3.85-3.80 (m, 1H), 3.69-3.64 (m, 1H), 2.37 (s, 3H),
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1.57 (d, J = 7.2 Hz, 3H), 1.40 (d, J = 6.8 Hz, 3H), 1.27 (d, J = 6.4 Hz, 3H), 1.15 (d, J = 6.8 Hz,
3H); 13C {1H}NMR (100 MHz, CDCl3) δ 157.0, 156.8, 152.6, 142.1, 140.7, 140.1, 132.7, 130.4,
129.2, 128.2, 126.5, 124.6, 119.2, 118.5, 52.9, 48.6, 21.6, 20.7, 20.1, 19.7; FT-IR (KBr) 3044,
2981, 2925, 1727, 1625, 1544, 1473, 1447, 1413, 1373, 1271, 1241, 1208, 1134, 1084, 1058,
1017, 920, 837, 828, 809, 762, 684, 549 cm-1; HRMS (ESI) m/z calcd for C23H26ClN2O4S
[M+H]+: 461.1302, found: 461.1296.
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(Z)-6-Fluoro-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7j.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.47; yellow solid; yield 65% (144
mg); mp 303-304 °C; 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.4 Hz, 3H), 7.33-7.28 (m, 2H),
7.24 (d, J = 6.4 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 3.86-3.81 (m, 1H), 3.70-3.65 (m, 1H), 2.38 (s,
3H), 1.58 (d, J = 6.8 Hz, 3H), 1.41 (d, J = 6.4 Hz, 3H), 1.27 (d, J = 6.4 Hz, 3H), 1.16 (d, J = 6.8
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Hz, 3H); C {1H}NMR (150 MHz, CDCl3) δ 159.9 (d, JC-F = 244.5 Hz), 157.2, 156.9, 150.4,
142.1, 140.7, 140.3, 129.2, 126.5, 124.7, 120.4 (d, JC-F = 24 Hz), 118.9 (d, JC-F = 13.5 Hz),
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118.7 (d, JC-F = 9 Hz), 114.3 (d, JC-F = 24 Hz), 52.8, 48.6, 21.6, 20.7, 20.1, 19.7; F NMR (376
MHz, CDCl3, CF3COOH as internal reference = -76.55) -116.6; FT-IR (KBr) 3045, 2984, 2925,
1725, 1577, 1545, 1490, 1432, 1376, 1267, 1211, 1136, 1085, 1018, 883, 775, 755, 686, 549 cm-
1; HRMS (ESI) m/z calcd for C23H25FN2O4S [M+H]+: 445.1597, found: 445.1589.
(Z)-6-Formyl-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7k.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.33; colorless solid; yield 10% (23
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mg); mp 261-262 °C; H NMR (600 MHz, CDCl3) δ 10.04 (s, 1H), 8.11 (dd, J = 8.4, 1.8 Hz,
1H), 8.08 (d, J = 1.2 Hz, 1H), 7.82 (s, 1H), 7.69 (d, J = 7.8 Hz, 2H), 7.50 (d, J = 8.4 Hz, 1H),
7.20 (d, J = 8.4 Hz, 2H), 3.89-3.85 (m, 1H), 3.72-3.67 (m, 1H), 2.38 (s, 3H), 1.58 (d, J = 7.2 Hz,
3H), 1.41 (d, J = 7.2 Hz, 3H), 1.28 (d, J = 6.6 Hz, 3H), 1.17 (d, J = 6.6 Hz, 3H); 13C {1H}NMR
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(150 MHz, CDCl3) δ 190.0, 157.8, 156.7, 156.6, 142.3, 140.6, 140.5, 133.3, 133.0, 131.4, 129.3,
126.5, 124.9, 118.6, 118.3, 53.0, 48.7, 21.7, 20.8, 20.2, 20.1, 19.7; FT-IR (KBr) 2981, 2965,
2924, 2852, 1737, 1700, 1623, 1547, 1447, 1373, 1269, 1168, 1136, 1114, 1084, 1056, 103, 947,
907, 644, 810, 762, 684, 549 cm-1; HRMS (ESI) m/z calcd for C24H27N2O5S [M+H]+: 455.1641,
found: 455.1640.
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(Z)-6-Iodo-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide 7l. Analytical
TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.66; colorless solid; yield 70% (193 mg); mp
277-278 °C; 1H NMR (400 MHz, CDCl3) δ 7.86-7.83 (m, 2H), 7.67 (d, J = 7.6 Hz, 2H), 7.63 (s,
1H), 7.19 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 1H), 3.85-3.82 (m, 1H), 3.70-3.66 (m, 1H),
2.38 (s, 3H), 1.58 (d, J = 6.8 Hz, 3H), 1.41 (d, J = 6.8 Hz, 3H), 1.27 (d, J = 6.4 Hz, 3H), 1.15 (d,
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J = 6.4 Hz, 3H); C {1H}NMR (100 MHz, CDCl3) δ 156.8, 153.8, 142.2, 141.3, 140.7, 139.9,
137.3, 129.2, 126.5, 124.4, 120.2, 119.0, 87.8, 52.9, 48.6, 21.6, 20.7, 20.1, 19.7; FT-IR (KBr)
2981, 2924, 2850, 1727, 1543, 1451, 1371, 1275, 1140, 1083, 1057, 1014, 943, 903, 828, 810,
761, 683, 550 cm-1; HRMS (ESI) m/z calcd for C23H26IN2O4S [M+H]+: 553.0658, found:
553.0654.
(Z)-N,N-Diisopropyl-6-methoxy-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7m.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.34; colorless solid; yield 67% (153
mg); mp 264-265 °C; 1H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.66 (d, J = 7.2 Hz, 2H), 7.28
(s, 1H), 7.17 (d, J = 6.8 Hz, 3H), 6.97 (s, 1H), 3.86 (s, 4H), 3.70-3.67 (m, 1H), 2.37 (s, 3H), 1.59
(d, J = 6.8 Hz, 3H), 1.43 (d, J = 6.4 Hz, 3H), 1.27 (d, J = 6.4 Hz, 3H), 1.15 (d, J = 6.0 Hz, 3H);
13C {1H}NMR (100 MHz, CDCl3) δ 157.6, 157.5, 156.5, 148.7, 142.0, 141.5, 140.8, 129.2,
126.6, 123.5, 121.0, 118.5, 118.1, 110.7, 56.0, 52.7, 48.5, 21.6, 20.7, 20.2, 20.1, 19.7; FT-IR
(KBr) 3035, 2966, 2932, 1713, 1578, 1550, 1497, 1448, 1367, 1280, 1212, 1142, 1089, 1037,
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1017, 965, 904, 879, 814, 806, 768, 755, 680, 595, 553 cm-1; HRMS (ESI) m/z calcd for
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C24H29N2O5S [M+H]+: 457.1797, found: 457.1805.
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(Z)-N,N-Diisopropyl-6-methyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7n.
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Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.41; yellow solid; yield 78% (172
mg); mp 295-296 °C; 1H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.40
(d, J = 8.4 Hz, 1H), 7.33 (s, 1H), 7.24 (d, J = 8.4 Hz, 1H), 7.17 (d, J = 7.6 Hz, 2H), 3.88-3.83
(m, 1H), 3.70-3.64 (m, 1H), 2.42 (s, 3H), 2.37 (s, 3H), 1.59 (d, J = 7.2 Hz, 3H), 1.43 (d, J = 6.8
Hz, 3H), 1.26 (d, J = 6.8 Hz, 3H), 1.14 (d, J = 6.8 Hz, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ
157.65, 157.61, 152.3, 141.9, 141.7, 140.8, 134.8, 133.9, 129.1, 128.8, 126.5, 122.9, 117.9,
116.7, 52.7, 48.5, 21.6, 20.8, 20.6, 20.2, 20.0, 19.6; FT-IR (KBr) 3080, 3025, 2982, 2965, 2924,
1718, 1627, 1580, 1542, 1492, 1447, 1373, 1269, 1211, 1175, 1135, 1084, 1061, 1018, 948, 906,
843, 810, 772, 685, 592, 570, 548 cm-1; HRMS (ESI): m/z calcd for C24H29N2O4S [M+H+]:
441.1848, found: 441.1864.
(Z)-8-(tert-Butyl)-6-iodo-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7p. Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.61; yellow solid; yield 76%
1
(231 mg); mp 244-245 °C; H NMR (400 MHz, CDCl3) δ 7.80 (s, 1H)), 7.73 (s, 1H), 7.65 (s,
1H), 7.62 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 3.84-3.80 (m, 1H), 3.71-3.68 (m, 1H),
2.35 (s, 3H), 1.60 (d, J = 6.8 Hz, 3H), 1.49-1.46 (m, 12H), 1.28 (d, J = 6.0 Hz, 3H), 1.15 (d, J =
13
6.4 Hz, 3H); C {1H}NMR (100 MHz, CDCl3) 157.1, 156.1, 152.6, 142.0, 141.5, 140.7, 140.6,
139.2, 135.8, 129.2, 126.5, 122.6, 120.3, 88.2, 52.9, 48.6, 35.3, 29.9, 21.6, 20.7, 20.2, 20.1, 19.6;
FT-IR (KBr) 2966, 2924, 1737, 1630, 1541, 1479, 1369, 1282, 1211, 1147, 1086, 1017, 970,
904, 828, 765, 748, 674, 664, 592, 551 cm-1; HRMS (ESI) m/z calcd for C27H34IN2O4S [M+H]+:
609.1284, found: 609.1288.
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(Z)-6,8-tert-Butyl-N,N-diisopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7q.
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Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.40; colorless solid; yield 80% (215
mg); mp 242-243 °C; 1H NMR (400 MHz, CDCl3) δ 7.76 (s, 1H), 7.62 (d, J = 8.0 Hz, 3H), 7.36
(s, 1H), 7.15 (d, J = 8.0 Hz, 2H), 3.88-3.85 (m, 1H), 3.71-3.67 (m, 1H), 2.34 (s, 3H), 1.61 (d, J =
6.4 Hz, 3H), 1.49-1.47 (m, 12H), 1.36 (s, 9H), 1.26 (d, J = 6.4 Hz, 3H), 1.14 (d, J = 6.0 Hz, 3H);
13C {1H}NMR (100 MHz, CDCl3) 158.0, 157.0, 151.0, 147.3, 143.7, 141.9, 140.9, 137.6, 129.2,
128.4, 126.6, 123.7, 121.3, 117.9, 52.7, 48.6, 35.3, 34.9, 31.5, 30.1, 21.6, 20.7, 20.2, 20.1, 19.7;
FT-IR (KBr) 2961, 2871, 1731, 1629, 1586, 1543, 1479, 1451, 1371, 1271, 1018, 953, 903, 842,
810, 767, 689, 594, 552 cm-1; HRMS (ESI) m/z calcd for C31H43N2O4S [M+H]+: 539.2944,
found: 539.2958.
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(Z)-N,N-Diisopropyl-3-oxo-N'-tosyl-3H-benzo[f]chromene-2-carboximidamide
7r.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.46; colorless solid; yield 60% (143
mg); mp 290-291 °C. 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.05
(d, J = 9.2 Hz, 2H), 7.93 (d, J = 8.0 Hz, 1H), 7.68 (t, J = 8.0 Hz, 1H), 7.64 (d, J = 8.0 Hz, 2H),
7.58 (t, J = 8.0 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 7.12 (d, J = 8.0 Hz, 2H), 3.94-3.91 (m, 1H),
3.74-3.71 (m, 1H), 2.35 (s, 3H), 1.66 (d, J = 6.8 Hz, 3H), 1.50 (d, J = 6.8 Hz, 3H), 1.30 (d, J =
13
6.8 Hz, 3H), 1.16 (d, J = 6.8 Hz, 3H). C {1H}NMR (100 MHz, CDCl3) δ 157.9, 157.5, 154.3,
142.0, 140.9, 137.6, 134.4, 130.5, 129.4, 129.2, 128.7, 126.5, 122.0, 121.9, 116.9, 112.6, 52.8,
48.6, 21.6, 20.7, 20.2, 20.1, 19.7; FT-IR (KBr) 3058, 2991, 2934, 1716, 1573, 1539, 1477, 1440,
1367, 1279, 1213, 1139, 1087, 1015, 955, 901, 849, 817, 669, 552 cm-1; HRMS (ESI) m/z calcd
for C27H29N2O4S [M+H]+: 477.1848, found: 477.1860.
(Z)-N,N-Diisopropyl-N'-(methylsulfonyl)-2-oxo-2H-chromene-3-carboximidamide
7s.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.25; colorless solid; yield 72% (126
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mg); mp 249-250 °C. 1H NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 7.58-7.53 (m, 2H), 7.36 (d, J =
8.4 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 3.92-3.89 (m, 1H), 3.75-3.72 (m, 1H), 2.96 (s, 3H), 1.61 (d,
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J = 6.4 Hz, 6H), 1.30 (d, J = 6.4 Hz, 3H), 1.17 (d, J = 6.4 Hz, 3H); C {1H}NMR (100 MHz,
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CDCl3) δ 157.8, 157.7, 154.2, 141.4, 132.8, 129.0, 125.0, 123.4, 118.1, 117.1, 52.6, 48.3, 43.1,
20.6, 20.2, 20.1, 19.8; FT-IR (KBr) 2924, 2853, 1719, 1608, 1541, 1449, 1376, 1275, 1214,
1112, 1061, 1018, 961, 908, 816, 756, 726, 518 cm-1; HRMS (ESI) m/z calcd for C17H23N2O4S
[M+H]+: 351.1379, found: 351.1376.
(Z)-N,N-Diisopropyl-2-oxo-N'-(phenylsulfonyl)-2H-chromene-3-carboximidamide
7t.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.36; colorless solid; yield 80% (165
mg); mp 259-260 °C. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 6.8 Hz, 2H), 7.73 (s, 1H), 7.59-
7.53 (m, 2H), 7.44-7.42 (m, 1H), 7.38-7.30 (m, 4H), 3.88-3.85 (m, 1H), 3.69-3.66 (m, 1H), 1.58
(d, J = 6.8 Hz, 3H), 1.41 (d, J = 6.8 Hz, 3H), 1.26 (d, J = 6.0 Hz, 3H), 1.14 (d, J = 6.0 Hz, 3H);
13C {1H}NMR (100 MHz, CDCl3) δ 157.5, 157.4, 154.2, 143.6, 141.6, 132.9, 131.6, 129.0,
128.6, 126.5, 125.1, 123.3, 118.2, 117.1, 52.9, 48.6, 20.7, 20.2, 20.1, 19.7; FT-IR (KBr) 3036,
2969, 2934, 1720, 1628, 1608, 1545, 1482, 1444, 1366, 1278, 1262, 1143, 1088, 1013, 901, 802,
755, 690, 612, 547 cm-1; HRMS (ESI) m/z calcd for C22H25N2O4S [M+H]+: 413.1535, found:
413.1535.
(Z)-N'-((4-Chlorophenyl)sulfonyl)-N,N-diisopropyl-2-oxo-2H-chromene-3-
carboximidamide 7u. Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.40; colorless
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solid; yield 82% (183 mg); mp 293-294 °C. H NMR (400 MHz, CDCl3) δ 7.76 (s, 1H), 7.75 (d,
J = 8.8 Hz, 2H), 7.62-7.55 (m, 2H), 7.37-7.32 (m, 4H), 3.92-3.89 (m, 1H), 3.71-3.68 (m, 1H),
1.57 (d, J = 6.4 Hz, 3H), 1.39 (d, J = 7.2 Hz, 3H), 1.28 (d, J = 6.4 Hz, 3H), 1.17 (d, J = 6.8 Hz,
3H); 13C {1H}NMR (100 MHz, CDCl3) δ 157.6, 157.5, 154.2, 142.2, 141.5, 137.8, 133.1, 129.0,
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128.8, 128.0, 125.1, 123.4, 118.1, 117.2, 53.0, 48.7, 20.6, 20.1, 19.8; FT-IR (KBr) 3033, 2980,
2928, 1714, 1627, 1609, 1550, 1483, 1444, 1368, 1295, 1271, 1213, 1144, 1088, 1012, 903, 819,
804, 765, 747, 655, 623, 550 cm-1; HRMS (ESI) m/z calcd for C22H24ClN2O4S [M+H]+:
447.1145, found: 447.1149.
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(Z)-N,N-Diisopropyl-N'-((4-methoxyphenyl)sulfonyl)-2-oxo-2H-chromene-3-
carboximidamide 7v. Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.70; colorless
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solid; yield 79% (175 mg); mp 259-260 °C. H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.71 (d,
J = 8.4 Hz, 2H), 7.61-7.54 (m, 2H), 7.35-7.31 (m, 2H), 6.86 (d, J = 8.8 Hz, 2H), 3.91-3.86 (m,
1H), 3.82 (s, 1H) 3.72-3.67 (m, 1H), 1.59 (d, J = 6.8 Hz, 3H), 1.44 (d, J = 6.8 Hz, 3H), 1.27 (d, J
= 6.8 Hz, 3H), 1.15 (d, J = 6.4 Hz, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ 162.0, 157.5, 157.3,
154.2, 141.5, 135.8, 132.9, 129.0, 128.5, 125.0, 123.3, 118.2, 117.1, 113.7, 55.6, 52.7, 48.5, 20.7,
20.2, 20.1, 19.7; FT-IR (KBr) 3034, 2975, 2931, 2839, 1718, 1627, 1609, 1597, 1548, 1496,
1445, 1371, 1353, 1314, 1142, 1128, 1087, 1060, 1014, 901, 809, 790, 758, 677, 596, 556 cm-1;
HRMS (ESI) m/z calcd for C23H27N2O4S [M+H]: 443.1641, found: 443.1641.
(Z)-N,N-Diisopropyl-N'-(mesitylsulfonyl)-2-oxo-2H-chromene-3-carboximidamide
7w.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.43; yellow solid; yield 68% (154
1
mg); mp 289-290 °C. H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.51
(d, J = 7.6 Hz, 1H), 7.32-7.25 (m, 2H), 6.74 (s, 2H), 3.82-3.79 (m, 1H), 3.70-3.66 (m, 1H), 2.48
(s, 6H), 2.24 (s, 3H), 1.60 (d, J = 6.8 Hz, 3H), 1.47 (d, J = 7.2 Hz, 3H), 1.27 (d, J = 6.4 Hz, 3H),
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1.14 (d, J = 6.8 Hz, 3H); C {1H}NMR (100 MHz, CDCl3) δ 157.2, 157.1, 154.1, 140.9, 140.8,
138.3, 137.7, 132.8, 131.3, 129.0, 124.9, 123.3, 118.2, 116.9, 52.7, 48.4, 22.8, 21.0, 20.7, 20.4,
20.1, 19.9; FT-IR (KBr) 3037, 2970, 2933, 1721, 1626, 1607, 1540, 1540, 1481, 1445, 1364,
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1350, 1281, 1212, 1129, 1061, 1008, 971, 902, 854, 797, 758, 673, 596, 522 cm-1; HRMS (ESI)
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m/z calcd for C25H31N2O4S [M+H]+: 455.2005, found: 455.2005.
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(Z)-N-Benzyl-N-cyclohexyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide 7x. Analytical
TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.35; colorless solid; yield 9% (22 mg, 3:1
isomers); mp 205-206 °C. 1H NMR (600 MHz, CDCl3) δ 7.88 (s, 1H), 7.64 (d, J = 8.4 Hz, 0.5H),
7.64-7.60 (m, 2H), 7.52-7.50 (m, 0.6H), 7.42 (d, J = 8.4 Hz, 1H), 7.36 (t, J = 7.2 Hz, 1H), 7.33-
7.31 (m, 4H), 7.29-7.26 (m, 3H), 7.25-7.19 (m, 2H), 7.17 (d, J = 7.2 Hz, 1H), 7.10 (d, J = 7.2 Hz,
0.6H), 7.00 (d, J = 7.8 Hz, 2H), 5.02 (d, J = 15.6 Hz, 1H), 4.67 (s, 0.3H), 4.61 (d, J = 15.6 Hz,
1H), 4.56 (d, J = 17.4 Hz, 0.3H), 4.40 (d, J = 16.8 Hz, 0.3H), 3.58-3.54 (m, 1H), 2.38 (s, 0.9H),
2.32 (s, 3H), 2.02 (d, J = 12.6 Hz, 1H), 1.76-1.71 (m, 0.6H), 1.63-1.59 (m, 3.6H), 1.55-1.53 (m,
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2H), 1.39-1.33 (m, 3H), 1.14-1.07 (m, 2.4H), 1.00 (t, J = 12.6 Hz, 1.3H); C{1H} NMR (150
MHz, CDCl3) δ 160.5, 159.4, 157.6, 157.4, 154.4, 154.1, 143.7, 142.6, 142.4, 142.0, 140.5,
140.3, 137.7, 136.9, 133.2, 133.0, 129.2, 129.1, 129.0, 128.9, 128.6, 127.8, 126.8, 126.7, 126.6,
126.5, 125.2, 125.0, 122.3, 121.9, 118.1, 117.8, 117.3, 116.9, 60.7, 58.4, 49.2, 47.5, 32.1, 31.8,
31.0, 30.32, 30.3, 25.84, 25.8, 25.62, 25.6, 25.1, 21.7, 21.6; FT-IR (KBr) 3033, 3015, 2958,
2936, 2925, 2852, 1714, 1625, 1609, 1574, 1543, 1452, 1420, 1372, 1282, 1185, 1243, 1088,
1065, 997, 980, 907, 686, 555 cm-1; HRMS (ESI) m/z calcd for C30H31N2O4S [M+H]: 515.1999,
found: 515.2005.
(Z)-N-Cyclohexyl-N-isopropyl-2-oxo-N'-tosyl-2H-chromene-3-carboximidamide
7y.
Analytical TLC on silica gel, 2:3 ethyl acetate-hexane Rf = 0.35; colorless solid; yield 9 % (20
mg, 1:1 isomers); mp 271-272 °C. 1H NMR (600 MHz, CDCl3) δ 7.74 (s, 1H), 7.72 (s, 1H), 7.66
(t, J = 8.4 Hz, 4H), 7.61-7.56 (m, 4H), 7.37-7.31 (m, 4H), 7.17-7.16 (m, 4H), 3.90-3.87 (m, 1H),
3.74-3.72 (m, 1H), 3.37-3.33 (m, 1H), 3.18 (s, 1H), 2.88-2.87 (m, 1H), 2.47-2.39 (m, 2H), 2.38
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(s, 3H), 2.37 (s, 3H), 2.02 (d, J = 12.0 Hz, 1H), 1.85 (d, J = 12.0 Hz, 1H), 1.77-1.72 (m, 2H),
1.67 (d, J = 6.6 Hz, 3H), 1.41 (d, J = 7.2 Hz, 3H), 1.25-1.17 (m, 7H), 1.13 (d, J = 6.6 Hz, 3H),
1.10-1.00 (m, 9H); 13C{1H} NMR (150 MHz, CDCl3) δ 157.6, 157.52, 157.5, 154.3, 142.1,
141.6, 141.5, 140.83, 140.8, 132.9, 129.21, 129.2, 129.1, 129.07, 126.6, 125.1, 123.4, 123.3,
118.24, 118.2, 117.2, 117.1, 61.7, 57.9, 52.9, 49.8, 30.8, 30.3, 29.9, 29.3, 28.6, 26.7, 26.5, 25.62,
25.6, 25.4, 25.1, 21.7, 20.8, 20.2, 19.7; FT-IR (KBr) 2964, 2931, 2849, 1722, 1607, 1540, 1482,
1445, 1383, 1371, 1272, 1143, 1087, 906, 811, 754, 729, 690, 575, 547 cm-1; HRMS (ESI) m/z
calcd for C26H31N2O4S [M+H]: 467.1999, found: 467.2005.
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AUTHOR INFORMATION
Corresponding Author
*Email: tpunni@iitg.ernet.in.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTs
We thank the Science and Engineering Research Board (SERB) (SR/S1/OC-55/2011), the
Council of Scientific and Industrial Research (CSIR) (02(0088)/12/EMR-II) and the Ministry of
Human Resource Development (MHRD) (5-7/214-TS-VII) for financial support. We also thank
Central Instrumental Facility (CIF), Indian Institute of Technology for instrumental facilities, and
Mr. M. Sengoden, Department of Chemistry, Indian Institute of Technology Guwahati for his
help in manuscript preparation.
ASSOCIATED CONTENT
Supporting Information
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Crystal structures and CIF files of 6 and 7r, mass spectrum of the reaction mixture of 1a, 2a, 3a,
and 4a, and NMR spectra (1H and 13C) of 2b-c, 5, 6, 7a-n and 7o-y, and 2D (COSY and HSQC)
NMR and DEPT of 7a. This material is available free of charge via the Internet at
http://pubs.acs.org.
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