A Regioselective Metal-Free Construction of 3-Aroyl Coumarins by Csp2-H Functionalization

Article abstract of DOI:10.1021/acs.joc.6b02051

A successive metal-free TBHP-mediated regioselective C-H functionalization of coumarins toward expedient synthesis of 3-aroyl coumarins is unveiled. The ongoing method conducted through the reaction of either coumarins or coumarin-3-carboxylic acids with

Full text of DOI:10.1021/acs.joc.6b02051

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Note
A Regioselective Metal-Free Construction of 3-
Aroyl Coumarins by Csp2-H Functionalization
Farnaz Jafarpour, and Masoumeh Abbasnia
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02051 • Publication Date (Web): 01 Nov 2016
Downloaded from http://pubs.acs.org on November 1, 2016
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A Regioselective Metal-Free Construction of 3-Aroyl Coumarins by Csp2-H
Functionalization
Farnaz Jafarpour* and A. Masoumeh Abbasnia
School of Chemistry, College of Science, University of Tehran, P.O. Box 14155ꢀ6619,
Tehran, Iran. Eꢀmail: Jafarpur@khayam.ut.ac.ir
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ABSTRACT
A successive metalꢀfree TBHPꢀmediated regioselective CꢀH functionalization of coumarins
towards expedient synthesis of 3ꢀaroyl coumarins is unveiled. The ongoing method
conducted through the reaction of either coumarins or coumarinꢀ3ꢀcarboxylic acids with
aromatic aldehydes. The optimized reaction condition also worked well with benzyl alcohols
and styrenes as surrogates for aldehydes, which bear latent carbonyl functionality.
Occurrence of 3ꢀcarbonyl coumarins in pharmaceutically active compounds justifies their
1
versatility. 3ꢀAroyl coumarins in particular, are proved to display varying degrees of αꢀ
1
a
1b
glucosidase inhibitory and DPPH scavenging activity (Scheme 1, I), antibacterial (II) and
1
c
as coumarinꢀchalcone hybrids, antioxidant activities(III). Furthermore, as a fluorescent
2+
chemosensor, compound IV has shown a high affinity and selectivity for Pb which would
1d
be helpful in clarifying the cellular role of lead ions in vivo. Given that, many have made
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considerable endeavours towards the synthesis of these motifs. Among the traditional
methods,
Scheme 1. Interesting compounds with 3ꢀaroyl coumarin framework
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Scheme 2. Methods of direct 3ꢀcarbonylation of coumarins
Previous works:
X = H3a
CuO, TBHP
O
X
O
H
X = H3b
+
Ar
Ar
Ar
FeCl , TBHP
2
O
O
O
O
O
O
X = CO H4
2
AgNO , K S O
8
3
2
2
H
+
FeCl 5
3
Ar
O
X
Ar
TBHP
O
O
O
DABCO
This work :
No Transition Metal
TBHP, PhCl
and
R
+
Ar
O
O
O
O
KIO , when X = CH2
3
R = H, CO H
X = O, CH2
2
Ar
OH
O
H
TBHP
No Metal, No Solvent
+
Ar
O
O
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Knoevenagel condensation is the most widely used route in which salicylaldehydes and βꢀ
2
ketoesters are exploited as the starting materials. However, despite all virtues the
aforementioned reaction suffers from some drawbacks, namely the necessity of basic or
acidic conditions and/or a laborious synthetic procedure. Thus, lately efforts have been
focused on direct acylation of coumarins through metalꢀcatalyzed CꢀH functionalization
reactions (Scheme 2).
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3a
3b
To this end, Zhou et al. and Yuan et al. individually reported synthetic procedures in
which coumarins were coupled with aromatic aldehydes through metal catalysed reactions. In
another effort, Duan and coꢀworkers showed that 3ꢀaroyl coumarins could be achieved
through the reaction of coumarins with phenylglyoxylic acid with the aid of silver catalyst,
4
albeit in low yields. 3ꢀAroyl coumarins were also prepared by the reaction of benzylether
5
and oumarins promoted by FeCl
3
as the catalyst. Nonetheless, a setback relevant to these
methods, due to the use of metal catalysts, are incompatibility with instructions issued by
Green Chemistry. Instead, metalꢀfree reactions have recently come of age. Plethora of
reactions released have now been conducted through metalꢀfree reactions since they offer
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greener approaches which take advantages of costꢀeffective reactionꢀpromoters. Despite the
growing prevalence of these reactions, to the best of our knowledge, thus far no metalꢀfree
crossꢀdehydrogenative coupling (CDC) reaction for direct functionalization of coumarins has
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been precedented. Herein, we report a stateꢀofꢀtheꢀart metalꢀfree acylation of this motif via
crossꢀdehydrogenative coupling with aromatic aldehydes as well as benzyl alcohols which
obviates the foregoing impediments of metalꢀcatalyzed reactions. This approach benefits
from smooth proceedings, is devoid of any kind of metals, and is promoted solely by TBHP.
Among metalꢀfree reactions, there are rare examples being promoted merely by TBHP as a
8
catalyst without any contribution of halide salts or other oxidants. This reaction is notable
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from another aspect since the competing aldehyde oxidation to its benzoic acid fails to
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outperform coupling procedure.
Table 1. Screening optimal conditions
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a
Entry
Initiator
TBHP
DTBP
Additive
Solvent
neat
Yield%
1
2
57
neat
52
3
K
2
S
2
O
8
neat
trace
50
4
TBHP/DTBP
AIBN
neat
5
neat
trace
trace
trace
40
6
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBAI
TBAB
TBAC
neat
7
neat
8
neat
9
K
2
CO
3
neat
trace
45
10
EtOAc
ACN
DCE
11
12
13
14
15
48
35
H
2
O
25
PhCl
70
TEMPO
PhCl
0
a
Reaction conditions: Coumarin (0.3 mmol), benzaldehyde (4 equiv.), TBHP (4 equiv., 70% in water) were
heated in a sealed tube at 100 °C for 20 h.
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First, we set out to functionalize coumarin regioselectively at Cꢀ3 by benzaldehyde using
TBHP which is endowed by the commencement of SET (single electron transfer) reactions.
To this end, coumarin was treated with benzaldehyde under TBHP at 100 °C for 20 h as the
model reaction. At the outset, the effects of different oxidants were screened as the oxidant
seemed to have the key role in conducting the reaction. Hence, an initial reaction was
accomplished using 4.0 equiv. of TBHP at 100 °C for 20 h under neat conditions which gave
rise to the desired product in 57% yield (Table 1, entry 1). When the oxidant was replaced
with DTBP, it still resulted in the favourable product, albeit in a lower yield, but no product
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was observed when K S O was employed (entries 2 and 3, respectively). In the next step, we
2
2
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added some additives in hope of increasing the reaction efficiency but they had
conspicuously deleterious effects on the yields (entries 6ꢀ9). In continuation, different
solvents were taken into account among which chlorobenzene furnished the best yield
(entries 10ꢀ14). Finally reducing the amount of TBHP to 2 equivs slightly reduced the yield.
We were delighted to find that these conditions, afforded aroylated coumarin regioselectively
at Cꢀ3 with 70% yield (entry 14). Introduction of coumarin to the optimized conditions in the
presence of a radical scavenger like TEMPO (10 equiv), suppressed the formation of the
desired aroyl compound markedly which indicated that a radical pathway could be involved
(entry 15).
Next, to investigate the scope and limitations of the regioselective direct carbonylation
process, various aromatic aldehydes and coumarins were exposed to the reaction condition
(Table 2). As we expected, pꢀ and mꢀmethylbenzaldehydes led to good yields (3bꢀ3c).
Employing highly electronꢀrich benzaldehyde increased the yield even more (3d). Also, halo
substituted arenes were tolerated under these circumstances, making the way for further
manipulation (3eꢀ3f). Cuminaldehyde as a coupling partner also resulted satisfactory yield of
the desired product (3g). The performance of this approach is also manifest in efficient
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conversion of sterically encumbered trimethoxy substituted benzaldehyde as well as
naphthaldehyde to their desired ketones (3h- 3i). Gratifyingly, various alkyl, alkoxy and halo
substituted coumarins were also tolerated under the optimized conditions and the reactions
proceeded smoothly furnishing the desired products in yields exceeding 65% (3jꢀ3m).
Unfortunately, electronꢀdeficient pꢀnitro benzaldehyde, did not participate in the crossꢀ
coupling reaction.
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Table 1. Substrate scope for construction of 3ꢀaroyl coumarins
a
All reactions were proceeded through the following conditions: Coumarin 1 (0.1 mmol), arylaldehyde 2 (4.0
equiv.), TBHP (4 equiv., 70% in water) in 0.5 mL PhCl were heated in a sealed tube at 100 °C for 20 h.
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To our delight, the approach was also viable for some heterocyclic carboxaldehydes. When
furfural, pyrroleꢀ and thiopheneꢀ2ꢀcarboxaldehydes were exposed to coumarin under reaction
conditions, the desired heteroaroyl coumarins 3o, 3p and 3q were obtained with satisfactory
yields, respectively. 1,2ꢀDihydro derivatives of these motifs which can be readily prepared
from reduction of the corresponding coumarins with sodium borohydride, are proved to show
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a marked selectivity for the inhibition of SIRT2 over SIRT1 (sirtuins’ inhibitors).
Surprisingly, when coumarinꢀ3ꢀcarboxylic acid was reacted with arene aldehydes, a tandem
decarboxylative/oxidative crossꢀcoupling reaction proceeded and good yields of aroyl
coumarins were obtained (Scheme 3). Although lately some reports on metalꢀfree
1
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decarboxylation have been released, this is the first example of decarboxylation of
coumarins under metal free conditions. Previous report in this field was also revealed by our
12
group using palladium catalyst.
Scheme 3. The reaction of coumarinꢀ3ꢀcarboxylic acid and benzaldehydes
Next our thoughts were stimulated about other approaches for construction of 3ꢀaroyl
coumarins. Gratifyingly, when benzylalcohol was utilized as an acyl source for coupling with
coumarin, the corresponding carbonylated coumarin was obtained albeit in low yield. A
slightly altered reaction condition with increasing amounts of TBHP and a higher reaction
temperature, afforded the desired products in moderate yields (Scheme 4).
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As a final step, inspired by Patel, Bhanage, Pan and Shah's work, we set out to gain the
desired product through the reaction of styrene with benzaldehyde (Scheme 5). Using slightly
altered reaction conditions the desired ketones were obtained, delightfully (See Table S2,
Supporting Information). Although the reaction yields are moderate to good, this is the first
report of acylation of a heterocyle via reaction with styrene.
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Scheme 4. Oxidative coupling of benzylalcohols and coumarins
HO
O
H
TBHP, neat
120 °C, 24h
Ar
Ar
+
O
O
O
O
O
O
O
O
O
O
O
O
O
Me
O
O
O
O
Me
3
a, 53%
3b, 57%
3d, 41%
Br
Me
O
O
O
O
O
O
O
Me
3e, 40%
3j, 44%
3k, 58%
a
Reaction conditions: Coumarin (0.1 mmol), benzylalcohol (0.1 mL), TBHP (8 equiv., 70% in water) were
o
heated in a sealed tube at 120 C for 24 h.
a
Scheme 5. Acylation of coumarin via the reaction with styrene
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a
Reaction conditions: Coumarin 1 (0.1 mmol), styrene (4.0 equiv.), TBHP (8 equiv., 70% in water), KIO
3
(2
b
equiv.) in 0.5 mL PhCl were heated in a sealed tube at 120 °C for 36 h. Due to difficulties in purification a
rough yield is given.
A tentative mechanism of the foregoing reaction has been shown below (Scheme 6). First, the
aryl carbonyl radical A may be generated with the aid of TBHP. Then this radical would
selectively attack coumarins at Cꢀ3 position and produce intermediate B which upon a
hydrogen radical loss would deliver the target molecule.
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Scheme 6. Plausible mechanism for regioselective Cꢀ3 acylation of coumarins
In summary, a regioselective direct carbonylation of coumarins via metalꢀfree crossꢀ
dehydrogenative coupling of coumarins and aromatic aldehydes has been developed which
provides an expedient access to 3ꢀaroyl coumarins. Benzylalcohol and styrene derivatives can
also be used in this term enabling one to reach the same products with various reagents.
Another privilege offered by this approach is that an in situ decarboxylation takes place
simultaneously over the coupling process allowing this procedure to be extended for
coumarinꢀ3ꢀcarboxylic acids. Good tolerance towards different functional groups renders this
method efficient and provides a simple alternative to its precedents.
EXPERIMENTAL SECTION
Typical Experimental Procedure for Metal-Free Direct Carbonylation of Coumarins. A
vial equipped with a stir bar was charged with coumarin (0.1 mmol), arylaldehyde (4 equiv)
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and TBHP (4 equiv). Chlorobenzene (0.5 mL) was added and the vial was capped. The
resulting mixture was heated in an oil bath at 100 °C for 20 h. Removal of the solvent gave a
crude mixture which was purified by flash column chromatography (hexane/EtOAc gradient)
and recrystallization was conducted either using diethyl ether or a mixture of diethyl
ether/hexane.
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2c
3-Benzoyl-2H-chromen-2-one (3a). White crystal (18 mg, 70%), mp 131ꢀ133 °C (Ref.
1
1
34ꢀ136 °C). H NMR (300 MHz, CDCl
3
): δ 8.07 (s, 1H), 7.87 (d, J = 8.1 Hz, 2H), 7.58ꢀ7.66
1
3
1
(
m, 3H), 7.31ꢀ7.49 (m, 4H); C{ H} NMR (75 MHz, CDCl ): δ 191.7, 158.5, 154.7, 145.5,
3
136.2, 133.9, 133.7, 129.6, 129.2, 128.8, 128.6, 125.0, 118.2, 116.9. Anal. Calcd for
: C, 76.79; H, 4.03. Found: C, 77.07; H, 4.16.
16 10 3
C H O
3-(4-Methylbenzoyl)-2H-chromen-2-one (3b). White Crystal (19 mg, 73%), mp 127ꢀ129
2c
1
°C (Ref. 132ꢀ134 °C). H NMR (300 MHz, CDCl ): δ 8.05 (s, 1H), 8.00 (d, J = 8.1 Hz, 1H),
3
7.79(d, J= 8.1 Hz, 1H), 7.62 (dd, J= 7.8 Hz, J= 1.5 Hz, 2H), 7.26ꢀ7.40 (m, 4H), 2.43 (s, 3H).
13
1
C{ H} NMR (75 MHz, CDCl
29.4, 129.2, 127.2, 124.9, 118.2, 116.8, 21.8. Anal. Calcd for C17
Found: C, 77.53; H, 4.68.
3
): δ 191.3, 158.5, 154.7, 145.1, 144.9, 133.6, 133.5, 129.8,
1
H
12
O
3
: C, 77.26; H, 4.58.
1
3
-(3-Methylbenzoyl)-2H-chromen-2-one (3c). White Crystal (18 mg, 69%). HNMR (300
13
1
MHz, CDCl
3
): δ 8.07 (s, 1H), 7.60ꢀ7.74 (m, 4H), 7.27ꢀ7.44 (m, 4H), 2.42 (s, 3H). C{ H}
): δ 191.9, 158.5, 154.7, 138.5, 136.2, 134.7, 133.6, 129.9, 129.2,
128.4, 127.9, 127.2, 126.9, 125.0, 118.2, 116.9, 21.3. Anal. Calcd for C17 : C, 77.26; H,
.58. Found: C, 77.57; H, 4.72.
NMR (75 MHz, CDCl
3
12 3
H O
4
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3-(4-Methoxybenzoyl)-2H-chromen-2-one (3d). White Crystal (21 mg, 75%), mp 174ꢀ175
2d
1
°
C (Ref. 174ꢀ175 °C). H NMR (400 MHz
,
CDCl
3
): δ 8.02 (s, 1H), 7.88 (d, J = 8.8 Hz, 2H),
7
7
.65 (td, J = 8.8 Hz, 1.6 Hz, 1H), 7.58 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H),
13
1
.35 (t, J = 7.6 Hz, 1H), 6.95 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H). C{ H} NMR (100 MHz,
157.4, 154.7, 144.6, 133.3, 132.2, 129.0, 127.7, 124.9, 118.3, 116.9,
13.9, 55.6. Anal. Calcd for C17 : C, 72.85; H, 4.32. Found: C, 73.10; H, 4.42.
-(2-Bromobenzoyl)-2H-chromen-2-one (3e). White Crystal (19 mg, 58%), mp 120ꢀ121 °C
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CDCl ): δ 190.0, 164.3
,
3
1
12 4
H O
3
3b
1
(
3
Ref. 127ꢀ128 °C). H NMR (300 MHz, CDCl ): δ 8.41 (s, 1H), 7.66 (m, 2H), 7.65ꢀ7.74 (d,
13
1
J = 7.8 Hz, 1H), 7.27ꢀ7.51 (m, 5H). C{ H} NMR (75 MHz, CDCl ): δ 191.8, 158.0, 155.3,
3
147.7, 140.3, 134.5, 133.1, 132.2, 130.0, 129.8, 127.7, 125.5, 125.0, 119.7, 118.4, 117.0.
9 3
Anal. Calcd for C16H BrO : C, 58.38; H, 2.76. Found: C, 58.66; H, 2.90.
3-(3-Chlorobenzoyl)-2H-chromen-2-one (3f). White Crystal (19 mg, 66%), mp 124ꢀ125
1
°C. H NMR (300 MHz, CDCl ): δ 8.15 (s, 1H), 7.82 (d, J = 1.5 Hz, 1H), 7.74 (d, J = 7.8 Hz,
3
1
3
1
1
H), 7.66 (t, J = 8.7 Hz, 2H), 7.58 (d, J = 7.8 Hz, 1H), 7.36ꢀ7.46 (m, 3H). C{ H} NMR (75
MHz ,CDCl ): δ 190.6, 158.4, 154.9, 146.2, 137.9, 134.9 ,134, 133.7, 129.9, 129.4, 129.3,
27.6, 126.3, 125.1, 118.1, 117.0. Anal. Calcd for C16 ClO : C, 67.50; H, 3.19. Found: C,
7.80; H, 3.32.
3
1
6
H
9
3
3-(4-Isopropylbenzoyl)-2H-chromen-2-one (3g). White Crystal (21 mg, 72%), mp 135ꢀ136
1
°
C. H NMR (500 MHz, CDCl
3
): δ 8.03 (s, 1H), 7.83 (d, J = 7.4 Hz, 2H), 7.58ꢀ7.65 (m, 2H),
1
3
1
7
.32ꢀ7.40 (m, 4H), 2.95ꢀ3.00 (m, 1H), 1.27 (d, J = 7.0 Hz, 6 H). C{ H} NMR (100 MHz,
): δ 191.1, 158.5, 155.6, 154.7, 144.9, 134.0, 133.5, 130.0, 129.1, 127.4, 126.8, 125.0,
18.3, 116.9, 34.4, 23.6. Anal. Calcd for C H O : C, 78.06; H, 5.52. Found: C, 78.30; H,
CDCl
3
1
5
19
16
3
.63.
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7
-(2, 3, 4-Trimethoxybenzoyl)-2H-chromen-2-one (3h). Red Solid (24 mg, 70%), mp 228ꢀ
1
30 °C. H NMR (500 MHz, CDCl
3
): δ 8.04 (s, 1H), 7.55ꢀ7.60 (m, 3H), 7.27ꢀ7.37 (m, 2H),
1
3
1
.76 (d, J = 8.8 Hz, 1H), 3.92 (s, 3H), 3.82 (s, 3 H), 3.72 (s, 3 H). C{ H} NMR (100 MHz,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
CDCl ): δ 189.7, 158.7, 158.4, 154.5, 154.0, 142.1, 141.4, 133.0, 130.2, 129.2, 126.1, 125.0,
3
1
24.7, 118.6, 116.8, 107.3, 61.6, 60.9, 56.2. Anal. Calcd for C19
16 6
H O : C, 67.05; H, 4.74.
Found: C, 67.33; H, 4.87.
3b
3-Naphthoyl-2H-chromen-2-one (3i). White Crystal (21 mg, 68%), mp 251ꢀ252 °C (Ref.
1
252ꢀ253 °C). H NMR (500 MHz, CDCl ): δ: 8.56 (d, J = 8.5 Hz, 1H), 8.23 (s, 1H), 8.04 (d, J
3
=
=
8.2 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.76 (d, J = 7.1 Hz, 1H), 7.56ꢀ7.68 (m, 5H), 7.48 (t, J
13
1
7.5 Hz, 1H), 7.41 (d, J = 8.3 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H). C{ H} NMR (100 MHz,
) δ: 193.2, 158.1, 155.1, 146.6, 134.6, 134.0, 133.4, 130.7, 129.6, 129.5, 128.6, 128.2,
126.7, 125.5, 124.9, 124.3, 118.3, 116.9. Anal. Calcd for C H O : C, 79.99; H, 4.03. Found:
CDCl
3
2
0
12
3
C, 80.31; H, 4.16.
3-Benzoyl-7-methoxy-2H-chromen-2-one (3j). White Crystal (20 mg, 70%), mp 159ꢀ160
3b
1
°C (Ref. 150ꢀ151 °C). H NMR (300 MHz, CDCl
3
): δ 8.11 (s, 1H), 7.88 (d, J = 7.2 Hz, 2H),
7.61 (t, J = 7.2 Hz, 1H), 7.47ꢀ7.53 (m, 3H), 6.93 (dd, J = 8.7 Hz, 2.4 Hz, 1H), 6.89 (d, J = 2.4
1
3
1
Hz, 1H), 3.94 (s, 3H). C{ H} NMR (75 MHz, CDCl ): δ 191.0, 163.6, 157.7, 156.1, 145.4,
3
135.8, 132.4, 129.4, 128.5, 127.4, 121.9, 112.5, 110.9, 99.7, 55.0. Anal. Calcd for C17
12 4
H O :
C, 72.85; H, 4.32. Found: C, 73.12; H, 4.44.
3-Benzoyl-6-methyl-2H-chromen-2-one (3k). White Crystal (21 mg, 76%), mp 163ꢀ164 °C
14
1
(Ref. 157.7ꢀ158.9 °C). H NMR (300 MHz, CDCl ): δ 8.05 (s, 1H), 7.89 (d, J= 7.5 Hz, 2H),
3
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7.63 (t, J= 7.5 Hz, 1H), 7.28ꢀ7.52 (m, 5H), 2.45 (s, 3H). C{ H} NMR (75 MHz, CDCl
3
): δ
90.8, 157.6, 151.9, 144.5, 135.3, 133.7, 132.7, 129.9, 128.6, 127.8, 127.6, 125.8, 116.9,
15.6, 19.7. Anal. Calcd for C17 : C, 77.26; H, 4.58. Found: C, 77.55; H, 4.71.
1
1
12 3
H O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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59
60
3-Benzoyl-7-methyl-2H-chromen-2-one (3l). White Crystal (19 mg, 72%), mp 156ꢀ158 °C
1
4
1
(
Ref. 157ꢀ158 °C). H NMR (300 MHz, CDCl
.59 (t, J = 8.1 Hz, 1H), 7.44ꢀ7.48 (m, 3H), 7.14ꢀ7.18 (m, 2H), 2.48 (s, 3H). C{ H} NMR
75 MHz, CDCl ): δ 191.8, 158.6, 155.0, 145.7, 136.5, 133.6, 129.5, 128.9, 128.5, 126.3,
25.6, 117.0, 115.8, 22.0. Anal. Calcd for C H O : C, 77.26; H, 4.58. Found: C, 77.58; H,
3
): δ 8.05 (s, 1H), 7.85 (d, J = 8.1 Hz, 2H),
13
1
7
(
3
1
17 12
3
4.71.
3-(Furan-2-carbonyl)-2H-chromen-2-one (3o). Brown Solid (15 mg, 63%), mp 155ꢀ156 °C
3b
1
(
3
Ref. 157ꢀ158 °C). H NMR (400 MHz, CDCl ): δ 8.16 (s, 1H), 7.67ꢀ7.60 (m, 3H), 7.40 (d,
13
1
J = 8.4 Hz, 1H), 7.37ꢀ7.33 (m, 2H), 6.61 (dd, J = 3.6 Hz, 1.6 Hz, 1H). C{ H} NMR (100
MHz, CDCl ): δ 178.0, 154.8, 151.8, 147.7, 145.5, 133.8, 129.3, 128.8, 126.3, 125.0, 120.7,
3
8 4
118.1, 117.0, 112.7. Anal. Calcd for C14H O : C, 70.00; H, 3.36. Found: C, 70.26; H, 3.47.
3-(1-Methyl-1H-pyrrole-2-carbonyl)-2H-chromen-2-one (3p). Brown Solid (18 mg, 70%),
15
1
mp 148ꢀ150 °C (Ref. 162ꢀ163 °C). H NMR (300 MHz, CDCl ): δ 7.95 (s, 1H), 7.56ꢀ7.65
3
(m, 2H), 7.28ꢀ7.41 (m, 2H), 6.98 (s, 1H), 6.83 (d, J = 2.1 Hz, 1H), 6.19 (d, J = 2.1 Hz, 1H),
13
1
4
.1 (s, 3H). C{ H} NMR (75 MHz, CDCl
3
): δ = 179.8, 158.6, 154.3, 142.6, 133.2, 132.9,
130.9, 128.8, 127.9, 124.8, 123.3, 118.2, 116.9, 108.9, 37.7. Anal. Calcd for C15
H
11NO
3
: C,
71.14; H, 4.38; N, 5.53. Found: C, 71.42; H, 4.50; N, 5.70.
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3-(5-Methyl-thiophene -2-carbonyl)-2H-chromen-2-one (3q). Brown Solid (16 mg, 61%),
3
b
1
mp 150ꢀ151 °C (Ref. 153ꢀ154 °C). HNMR (500 MHz, CDCl
3
): δ 8.05 (s, 1H), 7.64 (t, J =
7.8 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 3.6 Hz, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.35
13
1
(
t, J = 7.6 Hz, 1H), 6.84 (d, J = 3.6 Hz, 1H), 2.6 (s, 3H). C{ H} NMR (100 MHz, CDCl ): δ
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
= 182.4, 158.3, 154.6, 152.3, 144.3, 140.6, 136.0, 133.5, 129.1, 127.2, 127.0, 125.0, 118.2,
1
16.9, 16.2. Anal. Calcd for C15
.87; S, 12.07.
10 3
H O S: C, 66.65; H, 3.73; S, 11.86. Found: C, 66.94; H,
3
3-(4-Fluorobenzoyl)-2H-chromen-2-one (3r). White Solid (13 mg, 47%), mp 165ꢀ166 °C
3b
1
(
Ref. 167ꢀ168 °C). HNMR (500 MHz, CDCl
3
): δ: 8.11ꢀ 8.15 (m, 2H), 7.91ꢀ7.94 (m, 2H),
7
7
.66ꢀ7.68 (m, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H),
13
1
3
.14ꢀ7.18 (m, 1H). C{ H} NMR (100 MHz, CDCl ) δ: 190.2, 166.2 (d, JCꢀF = 254.7 Hz),
158.5, 154.9, 145.7, 133.8, 132.3 (d, JCꢀF = 9.5 Hz), 129.3, 126.9, 125.1, 118.2, 117.0, 115.8
d, JC–F = 21.9 Hz, CH). Anal. Calcd for C16 FO : C, 71.64; H, 3.38. Found: C, 71.90; H,
.49.
(
H
9
3
3
ACKNOWLEDGMENTS
We acknowledge the University of Tehran for the financial support.
Supporting Information
1
13
Copies of H and C spectra of all synthesized compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
REFERENCES
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