A new strategy for the one pot synthesis of (aryloxyimino)ethylcoumarins promoted by CuCl2

Article abstract of DOI:10.3184/174751912X13247245983221

Cupric chloride showed efficient catalytic activity for the cross coupling reaction of arylboronic acids and (hydroxyi mino)ethylcoumarins at room temperature in the presence of NEt3 as base. A simple and convenient protocol for the synthesis of O-aryloxi

Full text of DOI:10.3184/174751912X13247245983221

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 5
JANUARY, 5–8
A new strategy for the one pot synthesis of (aryloxyimino)ethylcoumarins
promoted by CuCl2
Gargi Pal, Pranabes Bhattacharyya, Arunima Medda and Asish R. Das*
Department of Chemistry, University of Calcutta, 92, A.P.C.Road, Kolkata – 700009, India
Cupric chloride showed efficient catalytic activity for the cross coupling reaction of arylboronic acids and (hydroxyi
mino)ethylcoumarins at room temperature in the presence of NEt3 as base. A simple and convenient protocol for the
synthesis of O-aryloxime ethers having the highly base sensitive coumarin nucleus is reported. O-Aryloxime ethers
are important as they provide access to scaffolds for the generation of various biologically active compounds. They
are potential precursors to benzofurans and benzisoxazoles.
Keywords: cross coupling, (aryloxyimino)ethylcoumarins, phenylboronic acid, cupric chloride
O-Aryloxime ethers have received considerable interest as
they provide access to scaffolds for the generation of various
biologically active compounds. These useful synthetic inter-
mediates are potential precursors to benzofurans and benzisox-
azoles.1–3 Some benzisoxazole derivatives have been reported
with inhibitory effects against chaperone Hsp 90 protein and
monoamine oxidase. Others possess considerable cytokinin-
like and neuroleptic activities. Such motifs are also an integral
part of many natural products and drug molecules showing
anti-leishmanial activity,4 anti-androgenic effects,5 anti-hyper-
tensive effects,6 psychotropic effects7 and anti-inflammatory
activity.8
the formation of 3-(4-methylphenoxyiminoethyl)coumarin 3c,
an optimisation of this synthetic approach began with a
systematic study with several common copper(I) and (II) salts
(Table 1) in order to improve the reaction time and yield. CuI
and Cu(acac)2 failed to promote the cross-coupling process
(Table 1). Ligands such as BINAP or DMG did not take part
Table 1 Screening of copper catalystsa
O-aryloximes are generally prepared applying the
cross-coupling of ketoximes and aldoximes with carbon
electrophiles such as alkyl or aryl halides, aryl nitrates,
arenediazonium salts, epoxides, activated olefins, trialkyl
orthoformates, allylic carbonates, acetates, phosphate esters
and Michael acceptors.9 Another pathway is the condensation
reaction between carbonyl compounds and O-aryloxamines.10
Although numerous successful methods were developed,
synthesis of O-aryloxime ethers involving coumarin skeletons
remained unexplored. Compounds containing the coumarin
framework are widely occurring secondary metabolites that
occur naturally in several plant families, essential oils and have
been used as a fragrance in food and cosmetic products,11
moreover, it is also found in a variety of pharmacologically
active compounds.12 Almost from the beginning of the study of
coumarins, the attention of the investigation has been focused
on the possibility of their therapeutic activity.13,14 From the
literature, we investigated the application of a Chan-Lam-
Evans protocol to access (aryloxyimino)ethylcoumarins via
cross-coupling of (hydroxyimino)ethylcoumarins and arylbo-
ronic acids in the presence of Cu(OAc)2 and Et3N. Despite the
success of this methodology, a prolonged reaction time and a
poor yield of the desired product restricted the synthetic utility
of this method. Thus the pursuit of inexpensive and more
benign reaction conditions for this transformation remained a
challenge which prompted us to develop the CuCl2 mediated
cross-coupling reaction of (hydroxyoxyimino)ethylcoumarin
(1) and arylboronic acids (2) leading to a good yield of (arylo
xyimino)ethylcoumarins (3).
Entry Cu-catalyst
Ligand Time Yield of
/hb 3a/%c
1
2
3
4
5
Cu(OAc)2
CuI
Cu(acac)2
Cu(acac)2
Cu(OAc)2
–
–
48
72
72
72
72
60
0
0
0
–
DMG
BINAP
Trace
6
–
48
62
50
7
–
72
8
9
–
–
72
72
45
35
10
11
12
–
–
–
72
48
48
37
48
63
Using (hydroxyimino)ethylcoumarin (1a) and 4-methyl-
phenylboronic acid (2c) as model substrates, we investigated
the cross-coupling reaction in the presence of Cu(II) as reported
by Chan15,16 and Evans et al.17 Thus, 1 equiv. of both (hydroxy
imino)ethylcoumarin and Cu(OAc)2, and 2 equiv. of both
phenylboronic acid and an amine base, were allowed to react
at room temperature in dichloromethane with 4 Å molecular
sieves under ambient atmospheric conditions. Encouraged by
13
14
CuCl2
–
–
–
18
72
90
0
a Reaction conditions: 1a (1 mmol), 2c (1.5 mmol), copper
catalyst (1 mmol), NEt3 (5 mmol).
b Monitored by TLC.
* Correspondent. E-mail: ardchem@caluniv.ac.in,
ardas66@rediffmail.com
c Isolated yields.

6
JOURNAL OF CHEMICAL RESEARCH 2012
Table 3 CuCl2-promoted O-arylation of (hydroxyimino)ethylc
oumarin (1) with arylboronic acids (2)
in the coupling reaction (Table 1) and also the reaction did
not proceed in the absence of catalyst (Table 1). A series of
Cu-salts (Table 1) has been employed to see the efficacy of
the coupling process but the best result was achieved in the
presence of the catalytic system CuCl2/NEt3 (Table 1) where
the yield of the desired product increased remarkably (~90%)
within a short period of time.
The arylboronic acid in the reaction conditions forms triphe-
nylboroxine18 with generation of water. Thus dry powdered
4 Å molecular sieves were added to the reaction mixture and
following that biaryl ether formation was not only suppressed
but the product yields also increased to a large extent. In the
next step of optimising the procedure, we focused on the nature
of the amine bases because of the presence of the lactone ring
of the coumarin moiety. Also the cross-coupling process is
highly dependent on the nature of the amine, as it acts both as
a base and a ligand, and varies according to the specific copper
catalyst.15–17,19,20 As shown in Table 2, triethylamine was a
satisfactory choice where 5 equivalents were required for
optimal yields of 3c (Table 2). Amines such as pyridine, DBU
and DMAP either suppressed or did not improve the cross-
coupling reaction. Triethylamine is an active base with pKa 9.8
whereas pyridine, DBU and DMAP are passive bases as well
as highly nucleophilic in origin. The non-coordinating nature
of triethylamine on steric grounds confirmed its supremacy
over other organic bases. In addition, on switching the base
from Cs2CO3 to K2CO3 to K3PO4 no desired product formation
was observed.
Entry
R1
R2
Product
Yield/%a
1
2
3
4
5
6
H(1a)
H (2a)
3-Br (2b)
3a
3b
3c
3d
3e
3f
81
70
90
76
74
86
4-Me (2c)
4-CF3 (2d)
4-F (2e)
4-tBu (2f)
7
8
9
10
11
OMe(1b)
NEt2(1c)
H (2a)
3-Br (2b)
4-CF3 (2d)
4-F (2e)
4-tBu (2f)
3g
3h
3i
3j
83
71
75
76
88
3k
12
H (2a)
3l
82
a Isolated yields. The structure and purity of the products were
checked by 1H, 13C, HRMS, IR spectra and TLC.
structure. In the IR spectra, characteristic strong absorption
appeared at 1740 cm−1 and 1677 cm−1 due to the stretching
vibration of the ester carbonyl and C=N group respectively. 1H
NMR spectra showed a singlet at δ 2.32 for the methyl protons
of the benzene ring and a singlet at δ 2.45 for the methyl
protons attached to the imino group. Another singlet at δ 8.01
corresponding to the H-4 proton of the coumarin moiety and
the eight aromatic protons appeared within the region δ 7.59–
7.13. In all compounds, the 1H NMR spectra revealed only one
type of methyl proton (attached with –C=N– moiety) which
ensured the formation of only one type of geometrical isomer
and the E-stereochemistry was confirmed from the X-ray
single crystal analysis (Fig. 1) of 3-(4-tert butylphenoxyimino
ethyl)coumarin (3f) (Table 4) (CCDC 849002).
Changing the solvent from dichloromethane to 1,4-dioxane
to toluene resulted in retardation of the reaction (Table 2) and
in acetonitrile no desired product was obtained at all. So, a
polar non-coordinating solvent was required for the coupling
process. In order to improve the yield a prolonged reaction
time was also attempted. Thus we obtained (4-methylphenylo
xyimino)ethylcoumarin in 90% yield, by carrying out the
coupling reaction in the presence of the catalyst CuCl2, base
NEt3, solvent CH2Cl2 and 4 Å molecular sieves as desicant.
We then evaluated the scope and limits of this optimised
protocol with a set of electronically diverse arylboronic acids
(Table 3). The reaction proceeded well with both electron-rich
and electron deficient arylboronic acids and products were
1
obtained in excellent yields (purity was checked by H, 13C,
The mechanism of this reaction is not fully established
but we can speculate that cupric chloride forms a complex
with (hydroxyimino)ethylcoumarin (1) and transmetallation
occurs with aryl boronic acid (2). The resulting aryl-copper-
coumarin-complex then undergoes subsequent reductive
elimination to provide the (aryloxyimino)ethylcoumarins (3).
HRMS and TLC.). Electron-rich aryl boronic acids underwent
arylation most efficiently (Table 3). Reaction proceeded
satisfactorily in the presence of additional functional groups;
the coupled products 3b, 3e, 3h and 3j are more interesting
as these may allow further functionalisation of the products.
Spectral data of compound 3c was consistent with its assigned
Table 2 Optimisationa of bases and solvents
Entry
Base
Solvent
Time /h Yield of 3b /%b
1b
2c
3d
4d
5d
Pyridine
DMAP
Et3N
CH2Cl2
48
72
72
48
18
45
<20
30
CH2Cl2
Toluene
Dioxane
CH2Cl2
Et3N
52
Et3N
90
a Reaction conditions: 1a (1 mmol), 2c (1.5 mmol), CuCl2
(1 mmol).
b Amount of pyridine used: 2.5 mmol.
c Amount of DMAP used: 2 mmol.
d Amount of NEt3 used: 5 mmol.
Fig. 1 ORTEP diagram of the single-crystal X-ray structure of
(E)-3-(4-tert-butylphenoxyiminoethyl)coumarin.

JOURNAL OF CHEMICAL RESEARCH 2012
7
Table 4 Crystal data and refinement details of the compound
tetramethylsilane (TMS) was used as the internal standard. IR spectra
were recorded in KBr pellets in reflection mode on a Perkin-Elmer
RX-1 FTIR spectrophotometer. High resolution mass spectra were
obtained using a QTofMICRO YA263 mass spectrometer. A suitable
single crystal of compound 3f was mounted on a Bruker-AXS SMART
APEX II diffractometer equipped with a graphite monochromator.
All the reactions were monitored by TLC carried out on Merck
aluminium-blocked silica gel plates coated with silica gel G under UV
light and also by exposure to iodine vapour for detection. Melting
points were determined on a Köfler Block apparatus and are uncor-
rected. Synthetic grade chemicals from Sigma-Aldrich, Spectrochem
and E-Merck were used for carrying out the organic reactions. 3-
(Hydroxyimino)ethylcoumarin is readily obtained from 3-acetylcou-
marin and hydroxylamine. For column chromatography 230–400
mesh silica gel from Spectrochem was used. All the solvents used in
the reaction were distilled and dried over Na2SO4.
3f
1. (a) The chemical formula
(b) MW
C21H21N1O3
335.39 ( from XRD)
2. Temperature
296(2) K
3. The symmetry cell setting,
symmetry space group name H-M
Monoclinic, C12/C1
4. Cell dimensions
(a) Cell length a
(b) Cell length b
(c) Cell length c
(d) Alpha
26.9794(10)
11.1897(4)
13.5271(6)
90.00
114.935(2)
90.00
(e) Beta
(f) Gamma
5. Cell volume
3703.1(3)
8
Preparation of (aryloxyimino)ethylcoumarins: general procedure
In a two-necked round bottom flask (50 mL) equipped with a
guard tube and septum was added a mixture of partially crushed 4 Å
molecular sieves (0.35 g), CuCl2 (0.134g, 1 mmol), arylboronic
acid (1.5 mmol), (hydroxyimino)ethylcoumarin (1 mmol) and CH2Cl2
(15 mL.). The mixture was then stirred well and NEt3 (0.69 mL,
5 mmol) was added carefully by syringe. Stirring was continued at
room temperature for 18 h. After completion of the reaction (moni-
tored by TLC), the mixture was filtered through celite, eluted with
CH2Cl2 and the filtrate was collected. Removal of solvent under
reduced pressure and purification of the crude product by column
chromatography (silica gel 230–400 mesh) provided pure products in
good yields (70–91%).
3-(Phenoxyiminoethyl)coumarin (3a): Yield: (0.226 g, 81%); m.p.
115 °C; white crystalline solid; Rf = 0.46 (EtOAc: n-hexane = 1:9);
1H NMR (300 MHz, CDCl3): δ 8.02 (s, 1H), 7.60–7.55 (m, 2H),
7.38–7.23 (m, 6H), 7.08–7.03 (m, 1H), 2.46 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3): δ 162.3, 159.1, 156.9, 154.1, 141.9, 132.4, 129.3,
128.6, 124.6, 122.6, 118.7, 118.1, 116.6, 114.9, 14.9 ppm; HRMS:
m/e calculated for (M+H)+ 280.0973, found 280.0973; IR (KBr) cm−1:
1211, 1590 (–C=N–), 1717 (–O–C=O).
6. The number of formula units
in the unit cell (Z)
7. Diffraction radiation wavelength 0.71073
8. Absorption coefficient (mu)
9. F (000)
0.078
1384
10. (a) The diffractometer that
was used
Bruker-AXS SMART
APEX II diffractometer
equipped with a graph-
ite monochromator
(b) The range for
collecting data ( h, k, l )
h min
h max
k min
k max
l min
–37
41
–17
15
–20
20
l max
3-(3-Bromophenoxyiminoethyl)coumarin (3b):Yield: (0.250 g, 70%);
m.p. 140 °C; White crystalline solid; Rf = 0.37 (EtOAc: n-hexane =
1:9); 1H NMR (300 MHz, CDCl3): δ 8.02 (s, 1h), 7.61–7.56 (m, 2H),
7.47 (s, 1H), 7.38–7.26 (m, 2H), 7.17–7.14 (m, 3H), 2.45 (s 3H) ppm;
13C NMR (75 MHz, CDCl3): δ 162.3, 159.7, 157.8, 154.2, 142.1,
132.6, 130.4, 128.8, 125.6, 124.8, 124.3, 122.7, 118.7, 118.1, 116.6,
113.6, 15.1 ppm; HRMS: m/e calculated for (M+H)+ 358.0079,
found 358.0078; IR(KBr) cm−1: 1466.7, 1581.3 (–C=N–), 1720.0
(–O–C=O).
11. (a) Diffraction reflection number 26063
(b) The number of independent 6999
reflections
(c) Cell measurement reflections 4669
used
12. The programmes that were
used
SAINT and SADABS
13. R factor all
R factor gt
0.0914
0.0572
3-(4-Methylphenoxyiminoethyl)coumarin (3c): Yield: (0.264 g,
90%); m.p. 128 °C; yellow crystalline solid; Rf = 0.48 (EtOAc:
1
14. Refinement diffraction density
max
0.262
n-hexane = 1:9); H NMR (300 MHz, CDCl3): δ 8.01 (s, 1H), 7.59–
7.55 (m, 2H), 7.38–7.25 (m, 2H), 7.13 (m, 4H), 2.45 (s, 3H), 2.32
(s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 162.29 159.48, 157.15,
156.57, 154.15, 141.78, 132.36, 132.04, 130.85, 129.71, 128.68,
124.68, 123.58, 118.81, 118.12, 116.57, 114.97, 20.60,14.89 ppm;
HRMS: m/e calculated for (M+H)+ 294.1130, found 294.1132;
IR(KBr) cm−1: 1209.7, 1557.9, 1677.1 (–C=N–), 1740.4.
Refinement diffraction density min –0.257
15. Details of where the data has
been deposited and the accession
number.
CCDC 849002
3-(4-Trifluorophenoxyiminoethyl)coumarin (3d): Yield: (0.264 g,
76%); m.p. 130 °C; white crystalline solid; Rf = 0.32 (EtOAc:
n-hexane = 1:9); 1H NMR (300 MHz, CDCl3): δ 8.02 (s, 1H),
7.62–7.58 (m, 4H), 7.39–7.31 (m, 4H), 2.48 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3): δ 162.3, 161.4, 159.3, 158.2, 154.2, 142.2, 132.7,
128.7, 126.7, 126.7, 124.2, 118.6, 116.6, 114.7, 15.1 ppm; HRMS:
m/e calculated for (M+H)+ 348.0847, found 348.0844; IR(KBr) cm−1:
1096.8, 1163.4, 1231.3, 1327.6, 1611.5 (–C=N–), 1721.1 (–O–C=O)
3-(4-Fluorophenoxyiminoethyl)coumarin (3e): Yield: (0.220 g,
74%); m.p. 120 °C; white crystalline solid; Rf = 0.30 (EtOAc:
n-hexane = 1:9); 1H NMR (300 MHz, CDCl3): δ 7.93 (s, 1H),
7.54–7.48 (m, 2H), 7.31–7.09 (m, 4H), 6.99–6.92 (m, 2H), 2.38
(s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 162.3, 157.1, 154.2,
141.9, 132.5, 128.6, 124.7, 124.5, 118.7, 118.1, 116.4, 115.7, 14.9
ppm; HRMS: m/e calculated for (M+H)+ 298.0879, found 298.0875;
IR (KBr) cm−1: 1194, 1610 (–C=N–), 1722 (–O–C=O).
In conclusion, a highly efficient as well as a very simple
methodology for the synthesis of (aryloxyimino)ethylcoumari
ns has been developed using cupric chloride as the active
catalyst and NEt3 as base applying the cross-coupling of
arylboronic acids and (hydroxyimino)ethylcoumarin for the
first time to the best of our knowledge. In addition to the low
cost, low toxicity of the catalyst and tolerance towards various
electronically diverse substrates, the excellent yield of the
desired products and shorter reaction time will make this
approach potentially useful and attractive for the synthesis of
(aryloxyimino)ethylcoumarins.
Experimental
3-(4-tert-Butylphenoxyiminoethyl)coumarin (3f): Yield: (0.290 g,
1H NMR and 13C NMR spectral analysis were carried out on Bruker-
Advance Digital 300 MHz and 75.5 MHz instruments where
86%); m.p. 101 °C; yellow crystalline solid; Rf = 0.49 (EtOAc:
1
n-hexane = 1:9); H NMR (300 MHz, CDCl3): δ 8.01 (s, 1H), 7.57

8
JOURNAL OF CHEMICAL RESEARCH 2012
(t, J = 6 and 9 Hz, 2H), 7.38–7.26 (m, 4H), 7.17 (d, J = 6 Hz, 2H),
2.45 (s, 3H), 1.32 (s, 9H) ppm; 13C NMR (75 MHz, CDCl3): δ 162.3,
159.5, 157.0, 156.6, 154.1, 145.5, 143.1, 141.8, 132.3, 128.6, 126.1,
124.7, 118.8, 116.6, 114.7, 34.3, 31.5, 14.9 ppm; HRMS: m/e
calculated for (M+H)+ 336.1599, found 336.1599; IR (KBr) cm−1:
1215,1604 (–C=N–), 1722 (–O–C=O).
= 1:9); 1H NMR (300 MHz, CDCl3): δ 7.85 (s,1H), 7.28–7.13 (m, 4H),
3.21 (m, 2H), 7.07–6.84 (m, 2H), 6.56 (d, J = 8.4, 1H), 6.40 (s, 1H),
3.31–3.21 (m, 4H), 2.38 (s, 3H), 1.16–1.12 (m, 6H) ppm; 13C NMR
(75 MHz, CDCl3): δ 161.0, 159.3, 157.9, 157.0, 151.3, 142.7, 129.8,
129.2, 126.9, 122.2, 118.4, 116.3, 115.5, 114.9, 109.3, 108.1, 44.8,
15.0, 12.3 ppm; HRMS: m/e calculated for (M+H)+ 351.1708, found
351.1707; IR(KBr) cm−1: 1272.7, 1419.1, 1504.7, 1616.8 (–C=N–),
1723.1 (–O–C=O).
3-(Phenoxyiminoethyl)-7-methoxycoumarin (3g): Yield: (0.256 g,
83%); m.p. 119 °C; white crystalline solid; Rf = 0.44 (EtOAc:
1
n-hexane = 1:9); H NMR (300 MHz, CDCl3): δ 7.97 (s, 1H), 7.45
(d, J = 6Hz, 1H), 7.32 (t, J = 3 and 6Hz, 2H), 7.24 (d, J = 3Hz, 1H),
7.04 (t, J = 6 and 3Hz, 1H), 6.89–6.84 (m, 2H), 3.89 (s, 3H), 2.45
(s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 163.6, 159.9, 159.4,
157.4, 156.3, 142.1, 129.8, 129.4, 122.6, 115.1, 113.3, 112.6, 100.6,
56.0, 15.1 ppm; HRMS: m/e calculated for (M+H)+ 310.1079, found
310.1079; IR (KBr) cm−1: 1094, 1615 (–C=N–), 1725 (–O–C=O).
3-(3-Bromophenoxyiminoethyl)-7-methoxycoumarin (3h): Yield:
(0.276 g, 71%); m.p. 161 °C; white crystalline solid; Rf = 0.31 (EtOAc:
We acknowledge the financial support from University of
Calcutta. Both G.P and PB thanks CSIR, New Delhi, India
for their fellowships (grant no. 09/028(0792)/2010 EMR-I
and 09/028(0768)/2010). Crystallography was performed at
the DST-FIST, India-funded Single Crystal Diffractometer
Facility at the Department of Chemistry, University of
Calcutta.
1
n-hexane = 1:9); H NMR (300 MHz, CDCl3): δ 7.97 (s, 1H), 7.49–
7.46 (m, 2H), 7.25–7.16 ( m, 3H), 6.90–6.84 (m, 2H), 3.89 (s, 3H),
2.43 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 162.3, 159.8, 158.1,
156.2, 142.2, 130.3, 129.8, 125.4, 122.6, 120.5, 118.1, 113.6, 113.2,
112.3, 100.5, 55.8, 15.0 ppm; HRMS: m/e calculated for (M+H)+
388.0184, found 388.0183; IR(KBr) cm−1: 1223.6, 1465.8, 1618.0
(–C=N–), 1727.0 (–O–C=O).
Received 25 October 2011; accepted 14 December 2011
Paper 1100952 doi: 10.3184/174751912X13247245983221
Published online: 31 January 2012
References
3-(4-Trifluorophenoxyiminoethyl)-7-methoxycoumarin (3i): Yield:
1
2
3
4
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(0.283 g, 75%); m.p. 146 °C; white crystalline solid; Rf = 0.27 (EtOAc:
1
n-hexane = 1:9); H NMR (300 MHz, CDCl3): δ 7.912 (s, 1H), 7.52
(d, 8.7, 2H), 7.41 (d, J = 8.4, 1H), 7.27 (d, J = 8.7, 2H), 6.849–6.792
(m, 2H), 3.83 (s, 3H), 2.40 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3):
δ 163.7, 161.5, 159.6, 158.5, 156.3, 142.3, 129.8, 126.8, 126.8, 126.7,
126.7, 124.7, 124.3, 122.5, 120.5, 114.7, 113.3, 112.3, 100.5, 55.9,
15.1 ppm; HRMS: m/e calculated for (M+H)+ 378.0953, found
378.0954; IR(KBr) cm−1: 1096.1, 1237, 1614.6 (–C=N–), 1714.7
(–O–C=O).
5
6
7
8
9
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3-(4-Fluorophenoxyiminoethyl)-7-methoxycoumarin (3j): Yield:
(0.249 g, 76%); m.p. 134 °C; white crystalline solid; Rf = 0.29 (EtOAc:
M.N.S. Rad, K.A. Nezhad, F. Karimitabar and S. Behrouz, Synthesis, 2010,
1
1724.
n-hexane = 1:9); H NMR (300 MHz, CDCl3): δ 7.95 (s, 1H), 7.45
10 H. Goda, H. Ihara, C. Hirayama and M. Sato, Tetrahedron Lett., 1994, 35,
1565.
11 R.D.H. Murray, J. Mendez and S.A. Brown, The natural coumarins.
occurrence, chemistry and biochemistry, John Wiley and Sons: Chichester,
1982.
12 S. Chimichi, M. Boccalini, B. Cosimelli, G. Viola, D. Vedaldi and
F. Dall’Acque, Tetrahedron Lett., 2002, 43, 7473.
(d, J = 8Hz, 1H), 7.21–7.17 (m, 2H), 7.04–6.98 (m, 2H), 6.89-6.84
(m, 2H), 3.89 (s, 3H), 2.44 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3):
δ 163.5, 157.3, 156.2, 155.3, 142.0, 129.6, 120.7, 116.3, 116.2, 115.8,
115.5, 113.2, 112.3, 100.4, 55.8, 14.9 ppm; HRMS: m/e calculated
for (M+H)+ 328.0985, found 328.0986; IR(KBr) cm−1: 1198, 1499
(–C=N–), 1616.4, 1708 (–O–C=O).
3-(4-tert-Butylphenoxyiminoethyl)-7-methoxycoumarin (3k): Yield:
(0.321 g, 88%); m.p. 120 °C; yellow crystalline solid; Rf = 0.48
(EtOAc: n-hexane = 1:9); 1H NMR (300 MHz, CDCl3): δ 3.19 (s, 1H),
7.44 (d, J = 8.7Hz, 1H), 7.34 (d, J = 8.7Hz, 2H), 7.16 (d, J = 8.7Hz,
2H), 6.893–6.844 (m, 2H), 3.892 (s, 3H), 2.439 (s, 3H), 1.311 (s, 9H)
ppm; 13C NMR (75 MHz, CDCl3): δ 163.4, 162.3, 159.8, 157.0, 156.9,
156.1, 145.4, 141.9, 129.6, 126.0, 121.0, 114.7, 113.1, 112.5, 100.4,
55.8, 34.2, 31.5, 14.8 ppm; HRMS: m/e calculated for (M+H)+
366.1705, found 366.1708; IR(KBr) cm−1: 1229.7, 1502.5, 1614.2
(–C=N–), 1720.3 (–O–C=O).
13 M.E. Riveiro, N. De Kimpe, A. Moglioni, R. Vázquez, F. Monczor,
C. Shayo and C. Davio, Curr. Med. Chem., 2010, 17, 1325.
14 J.R. Hwu, R. Singha, S.C. Hong, Y.H. Chang, A.R. Das, I. Vliegen,
E.D. Clercq and J. Neyts, Antiviral Res., 2008, 77, 157.
15 P.Y.S. Lam, C.G. Clark, S. Saubern, J. Adams, M.P. Winters, D.M.T. Chan
and A. Combs, Tetrahedron Lett., 1998, 39, 2941.
16 D.M.T. Chan, K.L. Monaco, R.-P. Wang and M.P. Winters, Tetrahedron
Lett., 1998, 39, 2933.
17 D.A. Evans, J.L. Katz and T.R. West, Tetrahedron Lett., 1998, 39, 2937.
18 D.M.T. Chan, K.L. Monaco, R. Li, D. Bonne, C.G. Clark, P.Y.S. Lam,
Tetrahedron Lett., 2003, 44, 3863.
19 D. Maiti and S.L. Buchwald, J. Org. Chem., 2010, 75, 1791.
20 G. Mann and J.F. Hartwig, Tetrahedron Lett., 1997, 38, 8005.
3-(Phenoxyimino)-7-N,N-diethylaminocoumarin (3l): Yield: (0.287 g,
82%); m.p. 38 °C; green amorphous solid; Rf = 0.41 (EtOAc: n-hexane

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