Rh-Catalyzed aldehydic C-H alkynylation and annulation

Article abstract of DOI:10.1039/c9ob02670c

Novel Rh-catalyzed aldehydic C-H bond alkynylation and annulation for the in situ synthesis of chromones and aurones are described. It involves the sequential aldehyde C-H bond alkynylation of salicylaldehyde with in situ generated 1-bromoalkyne from 1,1-

Full text of DOI:10.1039/c9ob02670c

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Rh-Catalyzed aldehydic C–H alkynylation and
annulation†
Cite this: DOI: 10.1039/c9ob02670c
Maddali L. N. Rao * and Boddu S. Ramakrishna
Novel Rh-catalyzed aldehydic C–H bond alkynylation and annulation for the in situ synthesis of chro-
mones and aurones are described. It involves the sequential aldehyde C–H bond alkynylation of salicyl-
aldehyde with in situ generated 1-bromoalkyne from 1,1-dibromoalkene followed by annulation. This pro-
tocol shows good functional group tolerance including aryl, alkenyl, alkyl and heteroaryl-1,1-dibromo-
alkenes. The steric/electronic effect was demonstrated during the base-mediated in situ cyclization of
o-hydroxyynones to generate aurones.
Received 16th December 2019,
Accepted 23rd January 2020
DOI: 10.1039/c9ob02670c
rsc.li/obc
directly from 1,1-dibromoalkenes.12 Surprisingly this useful
approach has not been reported to date (Scheme 1b) and hence
Introduction
Metal-catalyzed C–H bond functionalizations have attracted we focused our efforts in this direction under Rh-catalyzed
much attention in the construction of complex molecular skel- conditions in continuation of our earlier studies.8
etons and scaffolds.1 Alkynes are ubiquitous functionalities
Utilization of 1,1-dichloroalkenes13 or 1-bromoalkynes14 in
and their synthesis through C–H bond alkynylations is one of combination with salicylaldehyde was earlier reported in the
the most appealing ways to append alkyne in the synthesis of synthesis of chromones under palladium catalysis. These reac-
internal alkynes.2 The regio-selectivity in C–H bond alkynyla- tions involve the nucleophilic addition of a phenolic group as
tions is usually controlled by directing groups3–5 and these a first step either to 1,1-dichloroalkenes13 or 1-bromoalkynes.14
groups also facilitate the C–H bond alkynylations under mild This nucleophilic addition is a competitive pathway in our pro-
reaction conditions.5 Of note, the directing groups used in C– posed study of directed C–H bond alkynylations of salicylalde-
H bond functionalizations are highly limited and require an hydes using 1,1-dibromoalkenes (Scheme 1b). Hence, it is
additional removal step as part of the synthetic maneuvering. challenging and requires viable catalytic protocol conditions to
In particular, utilization of phenolic –OH as a nucleophilic overcome the competitive pathways. This is to bring out the
directing group is highly advantageous in the preparation of desired reactivity of aldehydic C–H bond alkynylation for the
multifunctional molecular scaffolds.6 Given this, salicylalde- in situ preparation of o-hydroxyynones towards the synthesis of
hydes are often used to construct heterocycles7 by taking chromones and/or aurones.15 Herein, we describe the Rh-cata-
advantage of the o-hydroxy group in the well-established alde- lyzed in situ aldehydic C–H bond alkynylation and annulation
hyde C–H bond functionalization8 by arylation, olefin hydroa- towards the synthesis of chromones and aurones.
cylation, and dehydrogenative coupling reactions.9,10
Directed C–H bond alkynylations of aryl C–H bonds are well
known in the literature using electrophilic alkynylating
Results and discussion
reagents.3,4 However, aldehyde C–H bond alkynylation reac-
tions are limited due to their sensitivity and poor reactivity.11 For
The reaction screening commenced with salicylaldehyde (1a)
and 1-(2,2-dibromovinyl)-4-methylbenzene (2a) as the reaction
example, Li11a and Zhou11b independently reported Ir(III)-cata-
lyzed synthesis of o-hydroxyynones from salicylaldehydes and a
hypervalent iodine-alkynylating reagent (TIPS-EBX) (Scheme 1a).
The scope of this approach is limited to alkynylsilanes as part of
the EBX reagent. Importantly, the use of haloalkynes as alkynylat-
ing reagents is more useful as they can be in situ prepared
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, UP, India.
E-mail: maddali@iitk.ac.in; Fax: +91 512 259 7532; Tel: +91 512 259 7532
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c9ob02670c
Scheme 1 Directed aldehyde C–H bond alkynylation.
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Table 1 Optimization studiesa,b
Table 2 Scope of functionalized salicylaldehydesa,b
Base
(equiv.)
Yieldb
3aa/4aa (%)
Entry
Catalyst
Solvent
1
2
3
4
5
6
7
8
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl(CO)(PPh3)2
RhCl3/2PPh3
NaHCO3 (3)
Na2CO3 (3)
K3PO4 (3)
KOAc (3)
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
NMP
DMA
Toluene
1,4-Dioxane
DMA
DMA
DMA
DMA
DMA
55/13
48/13
59/17
46/18
24/19
63/10
26/15
62/12
70/10
9/0
20/24
59/14
74/7
49/19
41/13
18/20
Cs2CO3 (3)
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
K2CO3 (2)
K2CO3 (4)
K2CO3 (4)
K2CO3 (4)
K2CO3 (4)
9
10
11
12
13
14
15
16
RhCl(PPh3)3
Rh(CO)2(acac)
a Reaction conditions: 1a–1n (0.75 mmol), 2a (0.5 mmol), RhCl(CO)
(PPh3)2 (0.025 mmol), K2CO3 (2 mmol), DMA (2 mL), 90 °C, 5 h. b A
minor aurone product was formed.
a Reaction conditions: 1a (0.75 mmol), 2a (0.5 mmol), catalyst
(0.025 mmol), base, solvent (2 mL), 90 °C, 5 h. b Isolated yields.
partners under rhodium catalysis (Table 1). The initial use of and electron-deficient groups on salicylaldehyde was tolerated
RhCl(CO)(PPh3)2 as the catalyst yielded chromone 3aa and its during the C–H bond functionalization reaction to furnish the
structural isomer aurone 4aa in 55% and 13% yields, respect- chromone products 3aa–3na in good to excellent yields.
ively (entry 1). The screening of different bases revealed the
Encouraged by the reactivity of functionalized salicylalde-
effectiveness of K2CO3 (3 equiv.) to give 3aa in 63% yield and hydes, the scope of functionalized 1,1-dibromoalkenes was
4aa in 10% yield (entry 6). At the same time, other bases gave explored next. As shown in Table 3, salicylaldehyde (1a)
an inferior ratio of the distribution of the products (entries reacted with 2-aryl-1,1-dibromoalkenes (2b–2j) having methyl,
2–5). Different solvents such as DMSO, NMP, DMA, toluene methoxy and halogen groups as substituents under the opti-
and 1,4-dioxane were further screened, and it was found that mized conditions and gave the corresponding chromones
DMA was an effective solvent that furnished 3aa in 70% yield 3ab–3aj in 53–72% yields. The 1,3-dienyldibromides (2k–2m)
along with 4aa in 10% yield (entry 9). Delightfully, excess base also reacted smoothly to furnish 2-styrylchromones 3ak–3am
(4 equiv.) delivered the product 3aa in 74% yield (entry 13). in 56–65% yields.
Employing other Rh-catalysts did not improve the yield of the
It is worth noting that the reaction of alkyl substituted 1,1-
reaction (entries 14–16). Thus, the combination of catalytic dibromoalkenes 2n and 2o was facile with salicylaldehyde and
RhCl(CO)(PPh3)2 and K2CO3 (4 equiv.) in DMA at 90 °C for 5 h gave the corresponding chromones 3an and 3ao in 63% and
was found to be the optimized conditions for the synthesis of 76% yields, respectively. It is important to note that chro-
chromone 3aa in a high yield (entry 13).
mones 3ac and 3ah were found to exhibit anti-microbial
With the optimized conditions in hand, the scope of func- activity.16 The flindersiachromone 3ao and its derivatives iso-
tionalized salicylaldehyde (1a–1n) with 1,1-dibromoalkene 2a lated from plant species are known to possess anti-inflamma-
was investigated. The results are summarized in Table 2. tory and antitumor activities.17
Salicylaldehyde substituted with electron-donating groups
Of note, we have successfully prepared efloxate (3ob) in one
such as methyl and alkoxy groups delivered the corresponding step from salicylaldehyde 1o and 2-phenyl-1,1-dibromoalkene
chromones 3aa–3ea in 58–74% yields. Halogen containing (2b) in 61% yield (Scheme 2) and this is useful in the treat-
salicylaldehydes furnished the halogenated chromones 3fa–3ja ment of cardiac-related diseases.18
in 33–86% yields.
Since a mixture of chromone and aurone products was
Interestingly, the electron-deficient salicylaldehydes formed from salicylaldehyde and 1,1-dibromoalkene (Table 4),
bearing cyano, ester and acetyl groups also reacted efficiently we hypothesize that they arise most probably from the regio-
and delivered the corresponding chromones 3ka–3ma in selective cyclization of a single o-hydroxyynone intermediate.15
64–69% yields. Selective reactivity was demonstrated by iso- Thus, different ortho-substituted 2-aryl-1,1-dibromoalkenes
phthalaldehyde as it furnished only the formyl chromone 3na 2p–2t having the substitution of methyl, alkoxy and chloro
in 67% yield. Overall, the substitution of both electron-rich groups were investigated under the optimized protocol con-
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Table 3 Scope of functionalized 1,1-dibromoalkenesa,b
Scheme 2 Synthesis of efloxate.
Entry
1,1-Dibromoalkene
Product
Yield (%)
Table 4 Scope of sterically hindered aryl and heteroaryl 1,1-
dibromoalkenesa
1
2
3
4
2b, R = H
2c, R = OMe
2d, R = F
3ab, R = H
3ac, R = OMe
3ad, R = F
70
66
65
57
Entry 1,1-Dibromoalkene Product and yield
2e, R = Cl
3ae, R = Cl
5
6
2f, R = OMe
2g, R = Cl
3af, R = OMe
3ag, R = Cl
64
53
1
2
3
4
5
6
2p, R = Me
2q, R = Cl
2r, R = OMe
2s, R = OBn
2t, R = OPh
3ap, R = Me, 44%
3aq, R = Cl, 17%
3ar, R = OMe, 36% 4ar, R = OMe, 43%
3as, R = OBn, 36% 4as, R = OBb, 39%
4ap, R = Me, 22%
4aq, R = Cl, 51%
3at, R = OPh, 18%
4at, R = OPh, 39%
7
8
9
2h, R = H
2i, R = OMe
3ah, R = H
3ai, R = OMe
61
72
62
7
8
a Reaction conditions: 1a (0.75 mmol), 2p–2w (0.5 mmol), RhCl(CO)
(PPh3)2 (0.025 mmol), K2CO3 (2 mmol), DMA (2 mL), 90 °C, 5 h.
10
11
12
13
2k, R = H
2l, R = OMe
2m, R = Cl
3ak, R = H
3al, R = OMe
3am, R = Cl
60
65
56
63
To elucidate the reaction pathway, the following experi-
ments were performed. The role of the hydroxyl group was first
investigated by performing reactions with benzaldehyde and
2-methoxybenzaldehyde under the optimized conditions. In
these reactions, the expected products were not formed
(Scheme 3a) and the aldehydes were recovered. This shows
that the phenolic –OH acts as a directing group for the
observed reactivity. Next, 1-bromoalkyne 2i′ was used in place
of 1,1-dibromoalkene 2i when chromone 3ai was formed in
52% yield (Scheme 3b). This shows that the reaction proceeds
14
76
a Reaction conditions: 1a (0.75 mmol), 2b–2o (0.5 mmol), RhCl(CO)
(PPh3)2 (0.025 mmol), K2CO3 (2 mmol), DMA (2 mL), 90 °C, 5 h.
b Aurone was formed in a minor amount.
ditions. These reactions gave mixtures of the corresponding through the 1-bromoalkyne 2i′ intermediate. The steric effect
chromone 3ap–3at and aurone 4ap–4at products. in salicylaldehyde was also investigated with the use of 1p and
Furthermore, 2-heteroaryl-1,1-dibromoalkenes 2u–2w also it furnished only the aurone product 4pa in 12% yield
reacted with salicylaldehyde under the optimized reaction con- (Scheme 3c). This is by the literature,15 which highlights the
ditions and furnished a mixture of chromone 3au and aurones significance of steric effects in o-hydroxyynone cyclization.
4au–4aw. Overall, in the case of ortho-substitution and also the Furthermore, salicylaldehyde was treated with 1,1-dibromoalk-
heterocyclic 1,1-dibromides, the formation of aurone products ene 2a in the presence of a base and this reaction afforded
in major amounts highlights the steric/electronic effects in the (Z)-alkenyl bromide 3aa′ in 46% yield along with unreacted
course of o-hydroxyynone cyclization.
1-bromoalkyne 2a′ in 15% yield (Scheme 3d). This control reac-
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Scheme 4 Proposed catalytic cycle.
with para and ortho chloro substitutions, respectively, under
base-mediated conditions (Scheme 3g). These two control
experiments furnished a mixture of the corresponding chro-
mones and aurones (3ae, 3aq and 4ae, 4aq) as o-hydroxyynone
cyclization products. From this, we conclude that the steric/
electronic effect in o-hydroxyynones thus plays an important
role in the observed selectivity under our established
Rh-catalyzed conditions.
From the above mechanistic findings, we propose the cata-
lytic cycle as given in Scheme 4 for the formation of both chro-
mone and aurone products. The Rh-catalyst oxidatively inserts
initially at the aldehyde C–H bond of salicylaldehyde to form
rhodacycle A. The alkynyl bromide in situ generated from
1,1-dibromoalkene in the reaction with a base12a undergoes
oxidative addition11 to give the intermediate B. This undergoes
elimination of HBr to form the alkynylrhodium(III) species C.
Finally, reductive elimination of the Rh-species from C forms
ynone D along with the regeneration of the catalyst. Base-
mediated in situ cyclizations of ynone D through the 6-endo-dig
or 5-exo-dig process gives the chromone 3 or aurone 4 pro-
ducts, respectively.15 However, the alternate mechanism for
the formation of chromone via (Z)-alkenyl bromide as reported
in the literature14 cannot be ruled out in the case of meta and
para-substituted 1,1-dibromoalkenes based on our control
experiments (Schemes 3d and e).
Scheme 3 Mechanistic studies.
tion highlights the in situ generation of 1-bromoalkyne from
1,1-dibromoalkene and also the competitive formation of
(Z)-alkenyl bromide as an addition product, a possible inter-
mediate for the formation of chromone under metal-catalyzed
conditions.14 A one-pot two-step reaction was also performed
using salicylaldehyde (1a) and 1,1-dibromoalkene 2a under the
established conditions (Scheme 3e). This reaction gave chro-
mone 3aa in 58% yield and thus established the alternate
possibility for the nucleophilic addition pathway and its sub-
sequent intramolecular coupling for the generation of the
chromone product. However, when salicylaldehyde 1a was
treated with 1-chloro-2-(2,2-dibromovinyl)benzene 2q in the
presence of
a base, the expected ether-tethered alkenyl
bromide 3aq′ as the nucleophilic addition product was not
formed (Scheme 3f). This reaction but afforded the base
mediated 3-arylcoumarin product.7 This finding thus suggests
Conclusions
suppression of the nucleophilic addition pathway14 due to In summary, we have developed an efficient protocol for the
ortho steric effects in the case of o-substituted 1,1-dibromo- Rh-catalyzed in situ aldehydic C–H bond alkynylation and
alkenes. Again, the formation of aurone as a major isomer annulation from salicylaldehydes and 1,1-dibromoalkenes for
product in the case of o-substituted 1,1-dibromoalkenes thus the synthesis of chromones and aurones. The aldehyde C–H
indicates the C–H alkynylation of salicylaldehyde as the pre- bond alkynylation by 1,1-dibromoalkenes is directed by the
ferred pathway leading to the formation of o-hydroxyynone neighboring o-hydroxy group. Our reactions showed good func-
and its cyclization to give either aurone or chromone.
tional group tolerance with 2-aryl-, 2-alkenyl-, 2-alkyl- and
To further check the regio-selectivity in the product for- 2-heteroaryl-1,1-dibromoalkenes. We have also demonstrated
mation, we reacted chloro-substituted o-hydroxyynones 5 and 6 the steric effects of the substituted ynone during the base-
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mediated cyclization in the formation of chromone and 135.2, 135.0, 129.9, 129.2, 126.3, 125.1, 123.7, 117.9, 106.9,
aurone products.
21.7, 21.1. IR (KBr, cm−1): 3039, 2921, 1645, 1615, 1510, 1366,
818. HRMS (ESI): calcd for C17H15O2 [M + H]+ 251.1072; found
251.1073.
7-Methoxy-2-p-tolyl-4H-chromen-4-one (3ca).13 Colourless
solid (83 mg, 62%); mp 130–132 °C. 1H NMR (400 MHz,
CDCl3): δ = 8.12 (d, J = 8.7 Hz, 1H), 7.79 (d, J = 8.3 Hz, 2H),
7.31 (d, J = 8.2 Hz, 2H), 6.98–6.95 (m, 2H), 6.73 (s, 1H), 3.92 (s,
3H), 2.43 (s, 3H). 13C NMR (125 MHz, CDCl3): δ = 178.0, 164.3,
163.5, 158.1, 142.2, 129.9, 129.1, 127.1, 126.2, 117.9, 114.5,
106.9, 100.5, 56.0, 21.7. IR (KBr, cm−1): 3470, 2947, 2840, 1638,
1627, 1604, 1439, 1374, 1355, 1162, 818. HRMS (ESI): calcd for
C17H15O3 [M + H]+ 267.1021; found 267.1028.
6-p-Tolyl-8H-[1,3]dioxolo[4,5-g]chromen-8-one (3da). Colourless
solid (92 mg, 65%); mp 168–170 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.77 (d, J = 8.3 Hz, 2H), 7.53 (s, 1H), 7.30 (d, J =
8.1 Hz, 2H), 6.96 (s, 1H), 6.77 (s, 1H), 6.10 (s, 2H), 2.43 (s, 3H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 177.6, 163.2, 153.6,
152.9, 146.3, 142.2, 129.9, 129.0, 126.2, 119.0, 106.4, 102.6,
102.4, 98.2, 21.7. IR (KBr, cm−1): 2921, 1639, 1461, 1362, 1029,
821. HRMS (ESI): calcd for C17H13O4 [M + H]+ 281.0814; found
281.0811.
Experimental
General
The coupling reactions were performed in dry Schlenk tubes
under nitrogen atmosphere conditions. All the NMR (1H and
13C) spectra were recorded on a JEOL ECS-400/ECX-500
spectrometer in CDCl3 solvent. Infrared (IR) spectra were
obtained using a PerkinElmer FT/IR spectrometer and absorp-
tions are reported in reciprocal centimeters. High-resolution
mass spectra (HRMS) were obtained using Waters GCT
Premier-CAB155 and Waters-Q-Tof Premier-HAB213 instru-
ments with electron ionization and electrospray ionization
techniques. Melting points were determined using a Yamato
melting point apparatus. Standard procedures were followed to
dry various solvents used in coupling reactions. The functiona-
lized salicylaldehyde derivatives (1a–1p),19 1,1-dibromoalkenes
(2a–2w)12a,d,20 and 1-bromoalkyne (2i′)20c were prepared by the
literature known methods. All the commercially available
chemicals are used without further purifications.
8-Methoxy-2-p-tolyl-4H-chromen-4-one (3ea). Colourless
solid (78 mg, 58%); mp 208 °C. 1H NMR (400 MHz, CDCl3): δ =
7.86 (d, J = 8.3 Hz, 2H), 7.77 (dd, J = 8.1, 1.3 Hz, 1H), 7.34–7.30
Representative procedure for coupling reactions
The coupling reaction was performed by charging a dry (m, 3H), 7.18 (dd, J = 7.9, 1.2 Hz, 1H), 6.84 (s, 1H), 4.02 (s, 3H),
Schlenk tube with salicylaldehyde (1a) (91.6 mg, 1.5 mmol), 1- 2.43 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 178.7, 163.5,
(2,2-dibromovinyl)-4-methylbenzene (2a) (138 mg, 0.5 mmol), 149.2, 146.8, 142.4, 129.9, 129.1, 126.5, 125.0, 124.9, 116.6,
RhCl(CO)(PPh3)2 (17.3 mg, 0.025 mmol), K2CO3 (276.4 mg, 114.5, 106.8, 56.5, 21.7. IR (KBr, cm−1): 3053, 2944, 2844, 1636,
2 mmol) and DMA (2 mL) solvent. This mixture was stirred in 1601, 1579, 1376, 1280, 1061, 802, 748. HRMS (ESI): calcd for
a pre-heated oil bath at 90 °C for 5 hours. The reaction mixture C17H15O3 [M + H]+ 267.1021; found 267.1022.
was brought to rt, quenched with dilute HCl and extracted
6-Fluoro-2-p-tolyl-4H-chromen-4-one (3fa). Colourless solid
with ethyl acetate (30 mL). The organic content was washed (102 mg, 80%); mp 140–142 °C. 1H NMR (400 MHz, CDCl3): δ =
with water (15 mL) and brine (15 mL), dried with anhydrous 7.86 (dd, J = 8.2, 3.1 Hz, 1H), 7.81 (d, J = 8.3 Hz, 2H), 7.57 (dd,
MgSO4 and concentrated. The crude product was purified by J = 9.1, 4.1 Hz, 1H), 7.41 (ddd, J = 9.1, 7.6, 3.1 Hz, 1H), 7.33 (d,
silica gel column chromatography using ethyl acetate/hexane J = 8.1 Hz, 2H), 6.80 (s, 1H), 2.44 (s, 3H). 13C NMR (125 MHz,
as an eluent. The product chromone 3aa was obtained as a CDCl3): δ = 177.8, 164.2, 159.7 (d, JC–F = 245 Hz), 152.6, 142.7,
colorless solid (88 mg, 74%) along with aurone 4aa as a yellow 130.0, 128.8, 126.4, 125.3 (d, JC–F = 7.2 Hz), 122.0 (d, JC–F = 25.5
solid (9 mg, 7%).
Hz), 120.3 (d, JC–F = 7.7 Hz), 110.8 (d, JC–F = 23.4 Hz), 106.4,
The characterization data for all the products (3 and 4) are 21.7. IR (KBr, cm−1): 3069, 1639, 1625, 1583, 1481, 1180, 908,
given below.
817. HRMS (ESI): calcd for C16H12FO2 [M + H]+ 255.0821;
2-p-Tolyl-4H-chromen-4-one (3aa).14 Colourless solid (88 mg, found 255.0820.
1
74%); mp 95–97 °C. H NMR (400 MHz, CDCl3): δ = 8.23 (dd,
6-Chloro-2-p-tolyl-4H-chromen-4-one (3ga).13 Colourless
J = 8.0, 1.6 Hz, 1H), 7.82 (d, J = 8.3 Hz, 2H), 7.69 (ddd, J = 8.6, solid (117 mg, 86%); mp 172–174 °C. 1H NMR (400 MHz,
7.1, 1.6 Hz, 1H), 7.56 (d, J = 8.3 Hz, 1H), 7.43–7.39 (m, 1H), CDCl3): δ = 8.18 (d, J = 2.5 Hz, 1H), 7.79 (d, J = 8.3 Hz, 2H),
7.32 (d, J = 8.1 Hz, 2H), 6.80 (s, 1H), 2.44 (s, 3H). 13C NMR 7.62 (dd, J = 8.9, 2.5 Hz, 1H), 7.51 (d, J = 8.9 Hz, 1H), 7.32 (d,
(100 MHz, CDCl3): δ = 178.6, 163.7, 156.4, 142.4, 133.8, 129.9, J = 8.1 Hz, 2H), 6.78 (s, 1H), 2.44 (s, 3H). 13C NMR (125 MHz,
129.1, 126.4, 125.8, 125.3, 124.1, 118.2, 107.1, 21.7. IR (KBr, CDCl3): δ = 177.3, 164.0, 154.7, 142.8, 134.0, 131.2, 130.0,
cm−1): 3060, 2920, 1644, 1568, 1466, 1374, 1042, 855, 819, 756. 128.6, 126.4, 125.3, 125.0, 119.9, 107.0, 21.7. IR (KBr, cm−1):
HRMS (ESI): calcd for C16H13O2 [M + H]+ 237.0916; found 3072, 1638, 1614, 1568, 1439, 1035, 909, 864, 816. HRMS (ESI):
237.0910.
calcd for C16H12ClO2 [M + H]+ 271.0526; found 271.0521.
6-Bromo-2-p-tolyl-4H-chromen-4-one (3ha). Colourless solid
6-Methyl-2-p-tolyl-4H-chromen-4-one (3ba).13 Yellow solid
(89 mg, 71%); mp 145–147 °C. H NMR (400 MHz, CDCl3): δ = (108 mg, 68%); mp 191–192 °C. 1H NMR (400 MHz, CDCl3): δ =
8.01–8.00 (m, 1H), 7.81 (d, J = 8.3 Hz, 2H), 7.50–7.44 (m, 2H), 8.34 (d, J = 2.5 Hz, 1H), 7.81–7.75 (m, 3H), 7.46 (d, J = 8.9 Hz,
7.31 (d, J = 8.0 Hz, 2H), 6.77 (s, 1H), 2.46 (s, 3H), 2.43 (s, 3H). 1H), 7.32 (d, J = 8.1 Hz, 2H), 6.80 (s, 1H), 2.44 (s, 3H). 13C NMR
13C NMR (100 MHz, CDCl3): δ = 178.7, 163.6, 154.6, 142.2, (125 MHz, CDCl3): δ = 177.2, 164.1, 155.2, 142.8, 136.8, 130.0,
1
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128.7, 128.5, 126.4, 125.4, 120.2, 118.7, 107.1, 21.7. IR 13C NMR (100 MHz, CDCl3): δ = 190.6, 177.6, 164.2, 159.6,
(KBr, cm−1): 3072, 1639, 1602, 1566, 1436, 1264, 1034, 908, 143.1, 133.4, 132.0, 130.8, 130.1, 128.3, 126.5, 124.2, 119.7,
816. HRMS (ESI): calcd for C16H12BrO2 [M + H]+ 315.0021; 107.5, 21.8. IR (KBr, cm−1): 3038, 2839, 1699, 1642, 1601, 1357,
found 315.0026.
1180, 826, 815. HRMS (ESI): calcd for C17H13O3 [M + H]+
6,8-Dichloro-2-p-tolyl-4H-chromen-4-one (3ia). Colourless 265.0865; found 265.0861.
solid (98 mg, 64%); mp 160–162 °C. 1H NMR (400 MHz,
Ethyl 2-(4-oxo-2-phenyl-4H-chromen-7-yloxy)acetate (3ob).
CDCl3): δ = 8.08 (d, J = 2.5 Hz, 1H), 7.85 (d, J = 8.3 Hz, 2H), Colourless solid (99 mg, 61%); mp 116–118 °C. 1H NMR
7.71 (d, J = 2.5 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 6.81 (s, 1H), (400 MHz, CDCl3): δ = 8.16 (d, J = 8.8 Hz, 1H), 7.91–7.88 (m,
2.44 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 176.6, 163.8, 2H), 7.54–7.50 (m, 3H), 7.03 (dd, J = 8.9, 2.4 Hz, 1H), 6.96 (d,
150.6, 143.2, 133.8, 130.9, 130.1, 128.2, 126.5, 125.9, 124.6, J = 2.4 Hz, 1H), 6.78 (s, 1H), 4.75 (s, 2H), 4.31 (q, J = 7.1 Hz,
124.0, 106.7, 21.8. IR (KBr, cm−1): 3072, 1651, 1612, 1595, 2H), 1.32 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ =
1563, 1455, 1347, 921, 877, 867, 823. HRMS (ESI): calcd for 177.9, 168.1, 163.4, 162.3, 157.8, 131.8, 131.7, 129.2, 127.5,
C16H11Cl2O2 [M + H]+ 305.0136; found 305.0138.
126.3, 118.7, 114.4, 107.7, 101.8, 65.6, 61.9, 14.3. IR (KBr,
6,8-Dibromo-2-p-tolyl-4H-chromen-4-one (3ja). Colourless cm−1): 3490, 3068, 2982, 1756, 1643, 1627, 1607, 1450, 1374,
solid (66 mg, 33%); mp 172–174 °C. 1H NMR (400 MHz, 1209, 1170, 1094, 853, 772. HRMS (ESI): calcd for C19H17O5
CDCl3): δ = 8.28 (d, J = 2.4 Hz, 1H), 8.02 (d, J = 2.4 Hz, 1H), [M + H]+ 325.1076; found 325.1070.
7.88 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 6.82 (s, 1H),
2-Phenyl-4H-chromen-4-one (3ab).14 Yellow solid (78 mg,
2.45 (s, 3H). 13C NMR (125 MHz, CDCl3): δ = 176.6, 164.0, 70%); mp 94–96 °C. H NMR (400 MHz, CDCl3): δ = 8.24 (dd,
151.9, 143.2, 139.4, 130.1, 128.2, 127.9, 126.6, 126.2, 118.6, J = 7.9, 1.6 Hz, 1H), 7.95–7.93 (m, 2H), 7.71 (ddd, J = 8.6, 7.2,
113.2, 106.7, 21.8. IR (KBr, cm−1): 3069, 1649, 1613, 1553, 1.7 Hz, 1H), 7.58 (d, J = 8.3 Hz, 1H), 7.55–7.51 (m, 3H),
1449, 1423, 1346, 1290, 872, 822. HRMS (ESI): calcd for 7.45–7.41 (m, 1H), 6.86 (s, 1H). 13C NMR (100 MHz, CDCl3):
1
C16H11Br2O2 [M + H]+ 392.9126; found 392.9120.
δ 178.6, 163.6, 156.4, 134.0, 131.9, 131.8, 129.2, 126.5, 125.8,
4-Oxo-2-p-tolyl-4H-chromene-6-carbonitrile (3ka). Yellow 125.4, 124.0, 118.2, 107.7. IR (KBr, cm−1): 3062, 1646,
solid (88 mg, 67%); mp 212 °C. 1H NMR (400 MHz, CDCl3): δ = 1569, 1465, 1375, 1128, 768. HRMS (ESI): calcd for C15H11O2
8.55 (d, J = 2.1 Hz, 1H), 7.91 (dd, J = 8.7, 2.1 Hz, 1H), 7.81 (d, [M + H]+ 223.0759; found 223.0757.
J = 8.3 Hz, 2H), 7.67 (d, J = 8.7 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H),
2-(4-Methoxyphenyl)-4H-chromen-4-one (3ac).14 Yellow solid
6.83 (s, 1H), 2.46 (s, 3H). 13C NMR (125 MHz, CDCl3): δ = (84 mg, 66%); mp 152–154 °C. H NMR (400 MHz, CDCl3): δ =
176.5, 164.4, 158.1, 143.3, 136.1, 131.5, 130.1, 128.2, 126.5, 8.22 (dd, J = 7.9, 1.6 Hz, 1H), 7.89 (d, J = 9.0 Hz, 2H), 7.69 (ddd,
124.6, 119.9, 117.7, 109.5, 107.6, 21.8. IR (KBr, cm−1): 3036, J = 8.7, 7.2, 1.8 Hz, 1H), 7.56–7.54 (m, 1H), 7.43–7.39 (m, 1H),
2226, 1649, 1609, 1480, 1441, 1361, 1194, 1033, 904, 819. 7.02 (d, J = 8.9 Hz, 2H), 6.78 (s, 1H), 3.89 (s, 3H). 13C NMR
HRMS (ESI): calcd for C17H12NO2 [M + H]+ 262.0868; found (100 MHz, CDCl3): δ = 178.5, 163.7, 162.6, 156.3, 133.8, 128.2,
1
262.0864.
125.8, 125.3, 124.1, 123.9, 118.1, 114.6, 106.2, 55.6. IR (KBr,
Methyl 4-oxo-2-p-tolyl-4H-chromene-6-carboxylate (3la).21a cm−1): 3050, 1648, 1608, 1466, 1381, 1268, 827, 768. HRMS
Colourless solid (102 mg, 69%); mp 206 °C. 1H NMR (ESI): calcd for C16H13O3 [M + H]+ 253.0865; found 253.0862.
(400 MHz, CDCl3): δ = 8.90 (d, J = 2.1 Hz, 1H), 8.34 (dd, J = 8.7,
2-(4-Fluorophenyl)-4H-chromen-4-one (3ad).14 Yellow solid
1
2.2 Hz, 1H), 7.81 (d, J = 8.3 Hz, 2H), 7.61 (d, J = 8.8 Hz, 1H), (78 mg, 65%); mp 134–136 °C. H NMR (400 MHz, CDCl3): δ =
7.33 (d, J = 8.1 Hz, 2H), 6.82 (s, 1H), 3.96 (s, 3H), 2.44 (s, 3H). 8.23 (dd, J = 8.0, 1.5 Hz, 1H), 7.94 (dd, J = 8.9, 5.2 Hz, 2H),
13C NMR (125 MHz, CDCl3): δ = 177.9, 165.9, 164.0, 158.8, 7.73–7.69 (m, 1H), 7.56 (d, J = 8.2 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H),
142.8, 134.5, 130.0, 128.6, 128.3, 127.4, 126.4, 123.8, 118.6, 7.22 (t, J = 8.6 Hz, 2H), 6.78 (s, 1H). 13C NMR (100 MHz, CDCl3):
107.4, 52.6, 21.7. IR (KBr, cm−1): 3433, 3093, 2956, 1729, 1654, δ = 178.5, 164.9 (d, JC–F = 252.1 Hz), 162.6, 156.3, 134.0, 128.7 (d,
1616, 1433, 1348, 1272, 1284, 1126, 1017, 821, 761. HRMS JC–F = 8.8 Hz), 128.1 (d, JC–F = 3.3 Hz), 125.9, 123.5, 124.0, 118.2,
(ESI): calcd for C18H15O4 [M + H]+ 295.0970; found 295.0970.
116.5 (d, JC–F = 22.0 Hz), 107.5 (d, JC–F = 1.2 Hz). IR (KBr, cm−1):
6-Acetyl-2-p-tolyl-4H-chromen-4-one (3ma). Colourless solid 3066, 1637, 1511, 1235, 908, 835, 753. HRMS (ESI): calcd for
1
(89 mg, 64%); mp 162–164 °C. H NMR (400 MHz, CDCl3): δ = C15H10FO2 [M + H]+ 241.0665; found 241.0663.
8.76–8.75 (m, 1H), 8.34–8.31 (m, 1H), 7.82 (d, J = 8.2 Hz, 2H),
2-(4-Chlorophenyl)-4H-chromen-4-one (3ae).14 Colourless
7.63 (d, J = 8.8 Hz, 1H), 7.34 (d, J = 8.0 Hz, 2H), 6.83 (s, 1H), solid (73 mg, 57%); mp 178–180 °C. 1H NMR (400 MHz,
2.70 (s, 3H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = CDCl3): δ = 8.22 (dd, J = 7.9, 1.4 Hz, 1H), 7.86 (d, J = 8.8 Hz,
196.7, 178.0, 164.1, 158.9, 142.9, 134.0, 132.9, 130.0, 128.5, 2H), 7.71 (ddd, J = 8.7, 7.1, 1.7 Hz, 1H), 7.57–7.55 (m, 1H), 7.50
127.3, 126.4, 123.6, 119.0, 107.3, 26.8, 21.7. IR (KBr, cm−1): (d, J = 8.8 Hz, 2H), 7.43 (ddd, J = 8.1, 7.2, 1.1 Hz, 1H), 6.81 (s,
3033, 1682, 1644, 1614, 1356, 1261, 829, 818. HRMS (ESI): 1H). 13C NMR (100 MHz, CDCl3): δ = 178.4, 162.4, 156.3, 138.0,
calcd for C18H15O3 [M + H]+ 279.1021; found 279.1022.
4-Oxo-2-p-tolyl-4H-chromene-6-carbaldehyde
134.1, 130.3, 129.5, 127.7, 125.9, 125.5, 124.0, 118.2, 107.8. IR
(3na). (KBr, cm−1): 2345, 1667, 1641, 1466, 1408, 1374, 1090, 828,
Colourless solid (89 mg, 67%); mp 184–186 °C. 1H NMR 772, 754. HRMS (ESI): calcd for C15H10ClO2 [M + H]+ 257.0369;
(400 MHz, CDCl3): δ = 10.10 (s, 1H), 8.70 (d, J = 2.0 Hz, 1H), found 257.0366.
8.24 (dd, J = 8.7, 2.0 Hz, 1H), 7.82 (d, J = 8.3 Hz, 2H), 7.69 (d,
J = 8.7 Hz, 1H), 7.34 (d, J = 8.1 Hz, 2H), 6.84 (s, 1H), 2.45 (s, 3H). (81 mg, 64%); mp 114–116 °C. 1H NMR (400 MHz, CDCl3):
2-(3-Methoxyphenyl)-4H-chromen-4-one (3af).14 Yellow solid
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δ = 8.23 (dd, J = 8.0, 1.6 Hz, 1H), 7.70 (ddd, J = 8.6, 7.1, 1.7 Hz, 754. HRMS (ESI): calcd for C17H13O2 [M + H]+ 249.0916; found
1H), 7.58–7.56 (m, 1H), 7.52–7.50 (m, 1H), 7.45–7.41 (m, 3H), 249.0913.
7.09–7.07 (m, 1H), 6.83 (s, 1H), 3.90 (s, 3H). 13C NMR
(E)-2-(4-Methoxystyryl)-4H-chromen-4-one (3al).21c Brown
(100 MHz, CDCl3): δ = 179.1, 163.4, 160.1, 156.4, 134.0, 133.3, solid (90 mg, 65%); mp 126–128 °C. 1H NMR (400 MHz,
130.3, 125.8, 125.4, 118.9, 118.3, 117.3, 111.9, 108.0, 55.6. IR CDCl3): δ = 8.20 (dd, J = 8.0, 1.4 Hz, 1H), 7.68 (ddd, J = 8.5, 7.3,
(KBr, cm−1): 3077, 2839, 1650, 1645, 1606, 1466, 1371, 1128, 1.5 Hz, 1H), 7.60–7.51 (m, 4H), 7.39 (t, J = 7.5 Hz, 1H), 6.94 (d,
1035, 756. HRMS (ESI): calcd for C16H13O3 [M + H]+ 253.0865; J = 8.7 Hz, 2H), 6.66 (d, J = 15.9 Hz, 1H), 6.35 (s, 1H), 3.86 (s,
found 253.0860.
3H). 13C NMR (100 MHz, CDCl3): δ = 178.5, 162.5, 161.3, 156.2,
2-(3-Chlorophenyl)-4H-chromen-4-one (3ag).13 Colourless 137.0, 133.8, 129.5, 127.9, 125.8, 125.1, 124.2, 118.0, 117.9,
solid (68 mg, 53%); mp 98–100 °C. 1H NMR (400 MHz, CDCl3): 114.6, 110.0, 55.6. IR (KBr, cm−1): 3473, 3063, 2837, 1633,
δ = 8.22 (dd, J = 8.0, 1.7 Hz, 1H), 7.92 (t, J = 1.9 Hz, 1H), 1602, 1561, 1511, 1465, 1387, 1255, 1171, 968, 756. HRMS
7.80–7.77 (m, 1H), 7.72 (ddd, J = 8.7, 7.1, 1.7 Hz, 1H), 7.58 (dd, (ESI): calcd for C18H15O3 [M + H]+ 279.1021; found 279.1028.
J = 8.4, 0.8 Hz, 1H), 7.52–7.41 (m, 3H), 6.81 (s, 1H). 13C NMR
(E)-2-(4-Chlorostyryl)-4H-chromen-4-one (3am). Brown solid
1
(100 MHz, CDCl3): δ = 178.4, 161.9, 156.3, 135.4, 134.2, 133.7, (79 mg, 56%); mp 180–182 °C. H NMR (400 MHz, CDCl3): δ =
131.7, 130.5, 126.5, 125.9, 125.6, 124.5, 124.0, 118.2, 108.3. IR 8.20 (dd, J = 7.9, 1.6 Hz, 1H), 7.69 (ddd, J = 8.6, 7.3, 1.7 Hz,
(KBr, cm−1): 3069, 2926, 1650, 1606, 1566, 1466, 1371, 1129, 1H), 7.58–7.51 (m, 4H), 7.42–7.38 (m, 3H), 6.76 (d, J = 16.0 Hz,
775, 756. HRMS (ESI): calcd for C15H10ClO2 [M + H]+ 257.0369; 1H), 6.36 (s, 1H). 13C NMR (100 MHz, CDCl3): δ = 178.6, 161.5,
found 257.0366.
156.1, 135.9, 135.7, 134.0, 133.6, 129.4, 129.0, 125.9, 125.2,
2-(3,4-Dimethoxyphenyl)-4H-chromen-4-one (3ah).21b Yellow 124.2, 121.0, 118.0, 111.0. IR (KBr, cm−1): 2926, 1635, 1464,
solid (86 mg, 61%); mp 144–146 °C. 1H NMR (400 MHz, 1386, 1091, 969, 756. HRMS (ESI): calcd for C17H12ClO2 [M +
CDCl3): δ = 8.23 (dd, J = 7.9, 1.6 Hz, 1H), 7.70 (ddd, J = 8.6, 7.3, H]+ 283.0526; found 283.0524.
1.7 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.44–7.39 (m, 2H), 6.99 (d,
2-Pentyl-4H-chromen-4-one (3an).21d Yellow liquid (68 mg,
J = 8.6 Hz, 1H), 6.80 (s, 1H), 3.99 (s, 3H), 3.97 (s, 3H). 13C NMR 63%); H NMR (400 MHz, CDCl3): δ = 8.18 (dd, J = 8.0, 1.7 Hz,
(100 MHz, CDCl3): δ = 178.5, 163.6, 156.3, 152.2, 149.4, 133.8, 1H), 7.64 (ddd, J = 8.6, 7.1, 1.6 Hz, 1H), 7.43 (d, J = 8.3 Hz, 1H),
125.8, 125.3, 124.3, 124.0, 120.2, 118.1, 111.3, 108.9, 106.5, 7.40–7.36 (m, 1H), 6.20 (s, 1H), 2.64–2.60 (m, 2H), 1.74 (p, J =
56.23, 56.21. IR (KBr, cm−1): 3472, 3066, 2936, 2837, 1641, 7.4 Hz, 2H), 1.41–1.35 (m, 4H), 0.93–0.90 (m, 3H). 13C NMR
1602, 1516, 1466, 1374, 1270, 1146, 1023, 772, 756. HRMS (100 MHz, CDCl3): δ = 178.6, 170.1, 156.7, 133.6, 125.8, 125.1,
1
(ESI): calcd for C17H15O4 [M + H]+ 283.0970; found 283.0975.
123.8, 118.0, 109.9, 34.4, 31.3, 26.6, 22.5, 14.1. IR (KBr, cm−1):
2-(3,4,5-Trimethoxyphenyl)-4H-chromen-4-one (3ai).21b 3492, 2957, 2862, 1658, 2932, 1466, 1384, 1221, 759. HRMS
Colourless solid (112 mg, 72%); mp 154–156 °C. 1H NMR (ESI): calcd for C14H17O2 [M + H]+ 217.1229; found 217.1220.
(400 MHz, CDCl3): δ = 8.23 (dd, J = 8.0, 1.6 Hz, 1H), 7.71 (ddd,
2-Phenethyl-4H-chromen-4-one (3ao).17b Yellow liquid
1
J = 8.7, 7.2, 1.7 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.45–7.41 (m, (96 mg, 76%); H NMR (400 MHz, CDCl3): δ = 8.18 (dd, J = 7.9,
1H), 7.14 (s, 2H), 6.81 (s, 1H), 3.96 (s, 6H), 3.93 (s, 3H). 13C 1.7 Hz, 1H), 7.65 (ddd, J = 8.7, 7.3, 1.8 Hz, 1H), 7.43 (d, J = 7.8
NMR (100 MHz, CDCl3): δ = 178.5, 163.4, 156.3, 153.7, 141.3, Hz, 1H), 7.40–7.37 (m, 1H), 7.32–7.28 (m, 2H), 7.24–7.20 (m,
133.9, 127.1, 125.8, 125.4, 124.0, 118.2, 107.5, 103.8, 61.2, 56.5. 3H), 6.15 (s, 1H), 3.09–3.05 (m, 2H), 2.96–2.92 (m, 2H).
IR (KBr, cm−1): 3060, 2989, 2943, 2839, 1651, 1569, 1508, 13C NMR (100 MHz, CDCl3): δ = 178.4, 168.6, 156.6, 139.8,
1338, 1243, 1128, 1001, 750. HRMS (ESI): calcd for C18H17O5 133.7, 128.8, 128.4, 126.7, 125.8, 125.1, 123.8, 118.0, 110.4,
[M + H]+ 313.1076; found 313.1073.
36.2, 33.1. IR (KBr, cm−1): 3026, 2920, 2850, 1654, 1465, 1383,
2-(Naphthalen-2-yl)-4H-chromen-4-one (3aj).13 Yellow solid 758. HRMS (ESI): calcd for C17H15O2 [M + H]+ 251.1072; found
1
(84 mg, 62%); mp 152–154 °C. H NMR (400 MHz, CDCl3): δ = 251.1071.
8.48 (s, 1H), 8.26 (dd, J = 7.9, 1.6 Hz, 1H), 7.99–7.88 (m, 4H),
2-o-Tolyl-4H-chromen-4-one (3ap).13 Liquid (52 mg, 44%);
7.75–7.71 (m, 1H), 7.64 (d, J = 7.9 Hz, 1H), 7.62–7.56 (m, 2H), 1H NMR (400 MHz, CDCl3): δ = 8.27 (dd, J = 8.0, 1.7 Hz, 1H),
7.46–7.42 (m, 1H), 6.98 (s, 1H). 13C NMR (100 MHz, CDCl3): 7.70 (ddd, J = 8.8, 7.2, 1.7 Hz, 1H), 7.54–7.46 (m, 2H),
δ = 178.6, 163.5, 156.5, 134.8, 134.0, 133.0, 129.2, 129.1, 129.0, 7.44–7.41 (m, 2H), 7.33 (d, J = 7.2 Hz, 2H), 6.49 (s, 1H), 2.49 (s,
128.2, 128.0, 127.2, 127.1, 125.9, 125.4, 124.1, 122.6, 118.3, 3H). 13C NMR (125 MHz, CDCl3): δ 178.4, 166.2, 156.6, 136.9,
108.0. IR (KBr, cm−1): 3058, 1640, 1565, 1464, 1382, 1347, 751. 133.9, 132.8, 131.4, 130.9, 129.4, 126.4, 125.9, 125.4, 124.0,
HRMS (ESI): calcd for C19H13O2 [M + H]+ 273.0916; found 118.2, 112.1, 20.7. IR (KBr, cm−1): 3065, 2926, 1651, 1465,
273.0913.
1370, 1036, 911, 759. HRMS (ESI): calcd for C16H13O2 [M + H]+
(E)-2-Styryl-4H-chromen-4-one (3ak).21c Yellow solid (74 mg, 237.0916; found 237.0910.
60%); mp 132–134 °C. 1H NMR (400 MHz, CDCl3): δ = 8.20
2-(2-Chlorophenyl)-4H-chromen-4-one (3aq).13 Colourless
(dd, J = 7.9, 1.6 Hz, 1H), 7.69 (ddd, J = 8.7, 7.3, 1.7 Hz, 1H), solid (11 mg, 17%); mp 104–106 °C. 1H NMR (400 MHz,
7.64–7.58 (m, 3H), 7.54 (d, J = 8.4 Hz, 1H), 7.44–7.38 (m, 4H), CDCl3): δ = 8.26 (dd, J = 7.9, 1.6 Hz, 1H), 7.71 (ddd, J = 8.6, 7.2,
6.80 (d, J = 16.0 Hz, 1H), 6.36 (s, 1H). 13C NMR (100 MHz, 1.7 Hz, 1H), 7.64 (dd, J = 7.4, 1.9 Hz, 1H), 7.56–7.51 (m, 2H),
CDCl3): δ = 178.6, 161.9, 156.1, 137.2, 135.1, 133.9, 130.0, 7.49–7.40 (m, 3H), 6.66 (s, 1H). 13C NMR (100 MHz, CDCl3):
129.1, 127.8, 125.8, 125.2, 124.2, 120.4, 118.0, 110.7. IR (KBr, δ = 178.3, 162.8, 156.8, 134.1, 133.1, 132.1, 131.9, 131.0, 130.8,
cm−1): 3474, 3060, 1651, 1644, 1614, 1562, 1383, 1123, 968, 127.2, 125.9, 125.5, 124.0, 118.4, 113.2. IR (KBr, cm−1): 3483,
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3067, 2924, 2853, 1651, 1466, 1372, 1128, 757. HRMS (ESI): NMR (100 MHz, CDCl3): δ = 184.8, 166.3, 147.2, 137.2, 136.0,
calcd for C15H10ClO2 [M + H]+ 257.0369; found 257.0363.
132.8, 131.0, 129.4, 124.9, 123.8, 121.7, 113.1, 111.7. IR (KBr,
2-(2-Methoxyphenyl)-4H-chromen-4-one (3ar).22a Brown cm−1): 2923, 2953, 1705, 1650, 1601, 1490, 1462, 1299,
1
solid (46 mg, 36%); mp 88–90 °C. H NMR (400 MHz, CDCl3): 1188, 1086, 885, 823, 755. HRMS (ESI): calcd for C15H10ClO2
δ = 8.23 (dd, J = 7.9, 1.7 Hz, 1H), 7.90 (dd, J = 7.8, 1.8 Hz, 1H), [M + H]+ 257.0369; found 257.0361.
7.67 (ddd, J = 8.7, 7.2, 1.7 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H),
(Z)-2-(2-Methylbenzylidene)benzofuran-3(2H)-one
(4ap).
1
7.50–7.45 (m, 1H), 7.42–7.38 (m, 1H), 7.15 (s, 1H), 7.10 (td, J = Yellow solid (26 mg, 22%); mp 92–94 °C. H NMR (400 MHz,
7.7, 0.9 Hz, 1H), 7.04 (d, J = 8.5 Hz, 1H), 3.93 (s, 3H). 13C NMR CDCl3): δ = 8.27 (dd, J = 7.2, 2.0 Hz, 1H), 7.84–7.81 (m, 1H),
(100 MHz, CDCl3): δ = 179.1, 161.0, 158.1, 156.6, 133.7, 132.5, 7.66 (ddd, J = 8.7, 7.3, 1.5 Hz, 1H), 7.34–7.30 (m, 3H),
129.4, 125.7, 125.0, 123.9, 120.98, 120.82, 118.1, 112.7, 111.9, 7.28–7.21 (m, 2H), 7.15 (s, 1H), 2.52 (s, 3H). 13C NMR
55.8. IR (KBr, cm−1): 3463, 3069, 2938, 2839, 1639, 1466, 1372, (125 MHz, CDCl3): δ = 184.9, 166.4, 147.2, 139.4, 137.0, 131.3,
1252, 1122, 1022, 756. HRMS (ESI): calcd for C16H13O3 131.0, 130.8, 130.0, 126.6, 124.9, 123.6, 121.9, 113.1, 110.1,
[M + H]+ 253.0865; found 253.0864.
20.4. IR (KBr, cm−1): 3060, 2923, 1703, 1649, 1594, 1458, 1299,
2-(2-(Benzyloxy)phenyl)-4H-chromen-4-one (3as).22b Yellow 1185, 1131, 1095, 886, 749. HRMS (ESI): calcd for C16H13O2
1
solid (60 mg, 36%); mp 70–72 °C. H NMR (400 MHz, CDCl3): [M + H]+ 237.0916; found 237.0919.
δ = 8.24 (d, J = 7.2 Hz, 1H), 7.86 (d, J = 6.9 Hz, 1H), 7.69–7.66
(m, 1H), 7.52–7.32 (m, 9H), 7.11–7.07 (m, 2H), 5.24 (s, 2H). 13
(Z)-2-(2-Chlorobenzylidene)benzofuran-3(2H)-one (4aq).23c
Yellow solid (66 mg, 51%); mp 134–136 °C. 1H NMR (400 MHz,
C
NMR (100 MHz, CDCl3): δ = 178.9, 161.6, 157.0, 156.6, 136.3, CDCl3): δ = 8.36 (dd, J = 7.8, 1.6 Hz, 1H), 7.83 (d, J = 7.6 Hz,
133.7, 132.5, 129.7, 128.8, 128.2, 127.1, 125.8, 125.1, 123.9, 1H), 7.67 (ddd, J = 7.9, 7.4, 1.4 Hz, 1H), 7.47 (dd, J = 7.9, 1.3
121.7, 121.2, 118.1, 113.5, 112.8, 70.7. IR (KBr, cm−1): 3065, Hz, 1H), 7.41–7.30 (m, 4H), 7.26–7.22 (m, 1H). 13C NMR
3034, 2928, 1642, 1466, 1371, 1248, 1121, 755. HRMS (ESI): (100 MHz, CDCl3): δ = 184.7, 166.3, 147.8, 137.2, 136.1, 132.4,
calcd for C22H17O3 [M + H]+ 329.1178; found 329.1176.
130.8, 130.6, 130.2, 127.2, 125.0, 123.9, 121.7, 113.1, 108.2. IR
2-(2-Phenoxyphenyl)-4H-chromen-4-one (3at). Yellow solid (KBr, cm−1): 1709, 1652, 1600, 1459, 1299, 1184, 885, 748.
1
(28 mg, 18%); mp 108–110 °C. H NMR (400 MHz, CDCl3): δ = HRMS (ESI): calcd for C15H10ClO2 [M + H]+ 257.0369; found
8.21 (dd, J = 8.3, 1.6 Hz, 1H), 7.92 (dd, J = 7.8, 1.7 Hz, 1H), 257.0368.
7.67–7.63 (m, 1H), 7.47–7.33 (m, 5H), 7.29–7.25 (m, 2H),
(Z)-2-(2-Methoxybenzylidene)benzofuran-3(2H)-one (4ar).23b
7.15–7.11 (m, 1H), 7.05 (s, 1H), 7.03–7.00 (m, 3H). 13C NMR Yellow solid (54 mg, 43%); mp 168–170 °C. 1H NMR (400 MHz,
(100 MHz, CDCl3): δ 178.8, 161.1, 156.6, 155.7, 133.8, 132.5, CDCl3): δ = 8.31 (dd, J = 7.8, 1.6 Hz, 1H), 7.81 (d, J = 7.0 Hz,
130.1, 129.8, 125.8, 125.2, 124.04, 124.00, 123.95, 123.74, 1H), 7.66–7.62 (m, 1H), 7.49 (s, 1H), 7.40–7.35 (m, 1H), 7.32 (d,
119.9, 119.2, 118.2, 112.6. IR (KBr, cm−1): 3065, 1645, 1575, J = 8.3 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H),
1485, 1466, 1371, 1237, 756. HRMS (ESI): calcd for C21H15O3 6.93 (d, J = 8.3 Hz, 1H), 3.91 (s, 3H). 13C NMR (100 MHz,
[M + H]+ 315.1021; found 315.1021.
CDCl3): δ = 184.9, 166.1, 159.0, 147.0, 136.8, 132.1, 131.6,
2-(Thiophen-2-yl)-4H-chromen-4-one (3au).13 Colourless 124.7, 123.4, 122.0, 121.4, 121.0, 113.0, 110.9, 107.4, 55.7. IR
1
solid (22 mg, 19%); mp 86–88 °C. H NMR (400 MHz, CDCl3): (KBr, cm−1): 2929, 2838, 1698, 1592, 1461, 1250, 1186, 1136,
δ = 8.21 (dd, J = 7.9, 1.7 Hz, 1H), 7.74 (dd, J = 3.7, 1.0 Hz, 1H), 1026, 883, 744. HRMS (ESI): calcd for C16H13O3 [M + H]+
7.69 (ddd, J = 8.6, 7.0, 1.6 Hz, 1H), 7.59 (dd, J = 5.0, 1.0 Hz, 253.0865; found 253.0860.
1H), 7.54 (d, J = 8.7 Hz, 1H), 7.44–7.40 (m, 1H), 7.19 (dd, J =
(Z)-2-(2-(Benzyloxy)benzylidene)benzofuran-3(2H)-one (4as).
5.0, 3.8 Hz, 1H), 6.74 (s, 1H). 13C NMR (100 MHz, CDCl3): δ = Yellow solid (65 mg, 39%); mp 96–98 °C. H NMR (400 MHz,
178.1, 159.2, 156.1, 135.3, 133.9, 130.5, 128.66, 128.65, 125.8, CDCl3): δ = 8.34 (dd, J = 7.9, 1.6 Hz, 1H), 7.83–7.80 (m, 1H),
125.4, 124.1, 118.1, 106.3. IR (KBr, cm−1): 3077, 1651, 1644, 7.64 (ddd, J = 8.5, 7.4, 1.4 Hz, 1H), 7.56 (s, 1H), 7.46 (d, J =
1621, 1569, 1464, 1385, 1127, 835, 755, 712. HRMS (ESI): calcd 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.35–7.31 (m, 3H),
1
for C13H9O2S [M + H]+ 229.0323; found 229.0323.
7.23–7.20 (m, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.97 (d, J = 8.2 Hz,
(Z)-2-(4-Methylbenzylidene)benzofuran-3(2H)-one (4aa).23a 1H), 5.20 (s, 2H). 13C NMR (100 MHz, CDCl3): δ = 184.8, 166.1,
Yellow solid (8 mg, 7%); mp 94–96 °C. 1H NMR (400 MHz, 158.1, 147.2, 136.76, 136.69, 132.3, 131.5, 128.8, 128.2, 127.3,
CDCl3): δ = 7.84–7.80 (m, 3H), 7.67–7.63 (m, 1H), 7.34 (d, J = 124.8, 123.4, 122.0, 121.9, 121.3, 113.0, 112.6, 107.4, 70.6. IR
8.3 Hz, 1H), 7.27 (d, J = 8.5 Hz, 2H), 7.22 (t, J = 7.5 Hz, 1H), (KBr, cm−1): 3064, 2929, 1704, 1645, 1596, 1454, 1300, 1251,
6.90 (s, 1H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 1185, 1132, 1096, 886, 752, 697. HRMS (ESI): calcd for
184.9, 166.2, 146.7, 140.7, 136.9, 131.7, 129.9, 129.7, 124.8, C22H17O3 [M + H]+ 329.1178; found 329.1178.
123.5, 121.9, 113.5, 113.1, 21.8. IR (KBr, cm−1): 3028, 2922,
2851, 1714, 1610, 1476, 1462, 1300, 756. HRMS (ESI): calcd for Yellow solid (62 mg, 39%); mp 105–106 °C. 1H NMR (400 MHz,
(Z)-2-(2-Phenoxybenzylidene)benzofuran-3(2H)-one
(4at).
C16H13O2 [M + H]+ 237.0916; found 237.0910.
CDCl3): δ = 8.42 (dd, J = 7.9, 1.6 Hz, 1H), 7.82–7.80 (m, 1H),
(Z)-2-(4-Chlorobenzylidene)benzofuran-3(2H)-one (4ae).23b 7.68–7.64 (m, 1H), 7.45 (s, 1H), 7.38–7.30 (m, 4H), 7.22 (t, J =
1
Yellow solid (12 mg, 9%); mp 136–138 °C. H NMR (400 MHz, 7.5 Hz, 2H), 7.14 (t, J = 7.4 Hz, 1H), 7.03 (d, J = 7.8 Hz, 2H),
CDCl3): δ = 7.86 (d, J = 8.6 Hz, 2H), 7.82 (dd, J = 7.7, 1.0 Hz, 6.90 (d, J = 8.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ = 184.8,
1H), 7.68 (ddd, J = 8.4, 7.4, 1.4 Hz, 1H), 7.43 (d, J = 8.6 Hz, 2H), 166.2, 163.7, 157.0, 137.0, 132.3, 131.4, 130.0, 124.9, 124.0,
7.34 (d, J = 8.2 Hz, 1H), 7.24–7.22 (m, 1H), 6.84 (s, 1H). 13C 123.9, 123.7, 123.6, 119.3, 118.5, 113.1, 106.8, 100.1. IR (KBr,
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cm−1): 3065, 2926, 1708, 1651, 1599, 1482, 1453, 1299, 1243, CDCl3): δ = 160.0, 154.1, 142.8, 133.86, 133.77, 132.0, 131.5,
1227, 1129, 1090, 886, 753. HRMS (ESI): calcd for C21H15O3 130.2, 130.1, 128.2, 127.2, 127.0, 124.7, 119.2, 116.9. IR (KBr,
[M + H]+ 315.1021; found 315.1027.
cm−1): 3042, 1725, 1606, 1453, 1121, 960, 754, 742. HRMS
(Z)-2-(Thiophen-2-ylmethylene)benzofuran-3(2H)-one (4au). (ESI): calcd for C15H10ClO2 [M + H]+ 257.0369; found 257.0365.
Yellow solid (48 mg, 42%); mp 126–128 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.80 (dd, J = 7.8, 1.0 Hz, 1H), 7.67–7.63 (m, 1H),
General procedure for the synthesis of o-hydroxyynones (5 and 6)
7.61 (d, J = 5.1 Hz, 1H), 7.55 (d, J = 3.7 Hz, 1H), 7.34 (d, J = 8.3
In an oven-dried 150 mL RB flask, 1,1-dibromoalkene
Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H), 7.18 (s, 1H), 7.15 (dd, J = 5.0,
(6 mmol) in THF (30 mL) was taken and cooled to −78 °C. At
3.7 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ = 184.0, 165.8,
this temperature, n-BuLi (12 mmol) was added dropwise and
145.4, 136.8, 135.7, 133.3, 131.9, 128.2, 124.7, 123.6, 122.4,
stirred for 1 hour. To this, salicylaldehyde (3 mmol) in THF
113.2, 107.2. IR (KBr, cm−1): 3094, 1699, 1645, 1594, 1456,
(10 mL) was added slowly for 10 minutes. After addition, the
1415, 1295, 1184, 1122, 1096, 882, 757, 709. HRMS (ESI): calcd
mixture was warmed to rt and stirred for 1 h followed by
for C13H9O2S [M + H]+ 229.0323; found 229.0325.
quenching with aq. NH4Cl. The THF was evaporated and the
(Z)-2-(Furan-2-ylmethylene)benzofuran-3(2H)-one (4av).
mixture was extracted with ethyl acetate. The crude product
Yellow solid (56 mg, 53%); mp 118–120 °C. 1H NMR (400 MHz,
was purified by column chromatography to obtain alcohol.
CDCl3): δ = 7.80–7.78 (m, 1H), 7.66–7.62 (m, 2H), 7.32 (d, J =
The formed alcohol was dissolved in dry DCM followed by por-
8.3 Hz, 1H), 7.22 (t, J = 7.2 Hz, 1H), 7.14 (d, J = 3.6 Hz, 1H),
tionwise addition of MnO2 in an interval of time. The reaction
6.90 (s, 1H), 6.60 (dd, J = 3.2, 1.8 Hz, 1H). 13C NMR (100 MHz,
was monitored by TLC, and the product mixture was passed
CDCl3): δ = 184.1, 165.9, 148.9, 145.6, 145.2, 136.8, 124.7,
through Celite and evaporated. The crude product was purified
123.6, 122.2, 117.4, 113.3, 113.1, 101.8. IR (KBr, cm−1): 3135,
by column chromatography to furnish the corresponding
3066, 1697, 1650, 1598, 1470, 1298, 966, 878, 752. HRMS (ESI):
o-hydroxyynones. The characterization data for o-hydroxyy-
calcd for C13H9O3 [M + H]+ 213.0552; found 213.0551.
nones (5 and 6) are as follows.
(Z)-2-((1H-Pyrrol-2-yl)methylene)benzofuran-3(2H)-one (4aw).
3-(4-Chlorophenyl)-1-(2-hydroxyphenyl)prop-2-yn-1-one (5).
Yellow liquid (46 mg, 43%); 1H NMR (400 MHz, CDCl3): δ =
Yellow solid (125 mg, 42%); mp 112–114 °C. 1H NMR
9.58 (s, 1H), 7.81 (dd, J = 7.7, 0.8 Hz, 1H), 7.63 (ddd, J = 8.6,
(400 MHz, CDCl3): δ = 11.69 (s, 1H), 8.09 (d, J = 7.8 Hz, 1H),
7.3, 1.4 Hz, 1H), 7.31 (d, J = 8.3 Hz, 1H), 7.24–7.20 (m, 1H),
7.63 (d, J = 7.1 Hz, 2H), 7.54 (t, J = 7.6 Hz, 1H), 7.43 (d, J =
7.16–7.14 (m, 1H), 6.97 (s, 1H), 6.73 (ddd, J = 3.7, 2.4, 1.4 Hz,
7.1 Hz, 2H), 7.02–6.98 (m, 2H). 13C NMR (100 MHz, CDCl3): δ =
1H), 6.37 (dt, J = 3.7, 2.5 Hz, 1H). 13C NMR (100 MHz, CDCl3):
182.2, 163.0, 137.8, 137.4, 134.4, 133.1, 129.4, 120.9, 119.6,
δ = 183.1, 164.7, 143.9, 136.1, 126.3, 124.7, 124.6, 123.5, 122.8,
118.4, 118.3, 94.6, 86.5. IR (KBr, cm−1): 3087, 2410, 2206, 1627,
118.5, 112.7, 111.6, 105.2. IR (KBr, cm−1): 3313, 1689, 1633,
1592, 1489, 1343, 1257, 1204, 1015, 825, 753. HRMS (ESI):
1591, 1424, 1298, 1189, 1112, 1090, 1037, 878, 752. HRMS
calcd for C15H10ClO2 [M + H]+ 257.0360; found 257.0369.
(ESI): calcd for C13H10NO2 [M + H]+ 212.0712; found 212.0713.
3-(2-Chlorophenyl)-1-(2-hydroxyphenyl)prop-2-yn-1-one (6).
(Z)-4,6-Dimethoxy-2-(4-methylbenzylidene)benzofuran-3(2H)-
1
Yellow solid (169 mg, 57%); mp 94–96 °C. H NMR (500 MHz,
one (4pa).23a Yellow solid (18 mg, 12%); mp 168–170 °C.
CDCl3): δ = 11.68 (s, 1H), 8.28 (dd, J = 8.2, 1.7 Hz, 1H), 7.73
1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 8.3 Hz, 2H), 7.24 (d,
(dd, J = 7.7, 1.6 Hz, 1H), 7.56–7.50 (m, 2H), 7.44 (td, J = 7.8, 1.6
J = 7.9 Hz, 2H), 6.77 (s, 1H), 6.40 (d, J = 1.8 Hz, 1H), 6.14 (d, J =
Hz, 1H), 7.34 (td, J = 7.6, 1.2 Hz, 1H), 7.02–6.99 (m, 2H). 13C
1.8 Hz, 1H), 3.96 (s, 3H), 3.92 (s, 3H), 2.39 (s, 3H). 13C NMR
NMR (125 MHz, CDCl3): δ = 182.2, 163.0, 137.8, 137.5, 135.2,
(125 MHz, CDCl3): δ = 180.9, 169.2, 169.0, 159.6, 147.6, 139.9,
133.5, 132.3, 129.9, 127.1, 121.0, 120.3, 119.7, 118.2, 92.0, 89.9.
131.3, 130.0, 129.7, 111.2, 94.2, 89.4, 56.4, 56.3, 21.7. IR (KBr,
IR (KBr, cm−1): 3067, 2211, 1625, 1472, 1250, 1156, 1014, 750,
cm−1): 2943, 1697, 1615, 1591, 1503, 1249, 1210, 1155, 1093,
711. HRMS (ESI): calcd for C15H10ClO2 [M + H]+ 257.0369;
817. HRMS (ESI): calcd for C18H17O4 [M + H]+ 297.1127; found
found 257.0369.
297.1129.
(Z)-2-(2-Bromo-1-p-tolylvinyloxy)benzaldehyde (3aa′). Colourless
solid (73 mg, 46%); mp 152–154 °C. 1H NMR (400 MHz,
CDCl3): δ = 10.76 (s, 1H), 7.91 (dd, J = 7.7, 1.8 Hz, 1H),
Conflicts of interest
7.41–7.36 (m, 3H), 7.15 (d, J = 8.1 Hz, 2H), 7.08 (t, J = 7.5 Hz,
1H), 6.81 (d, J = 8.4 Hz, 1H), 6.57 (s, 1H), 2.33 (s, 3H). 13C NMR
There are no conflicts to declare.
(100 MHz, CDCl3): δ = 189.3, 158.6, 153.0, 140.1, 135.9, 130.4,
129.9, 128.7, 125.7, 125.2, 122.7, 115.2, 95.5, 21.5. IR
(KBr, cm−1): 3033, 2923, 2853, 1736, 1683, 1607, 1264, 1180,
Acknowledgements
820, 753. HRMS (ESI): calcd for C16H14BrO2 [M + H]+ 317.0177;
found 317.0182.
We are happy to acknowledge the financial support provided
3-(2-Chlorophenyl)-2H-chromen-2-one (3aq″).23d Colourless by the Science and Engineering Research Board (SERB) under
solid (78 mg, 61%); mp 132–134 °C. 1H NMR (400 MHz, the Department of Science and Technology, New Delhi (grant
CDCl3): δ = 7.76 (s, 1H), 7.60–7.53 (m, 2H), 7.51–7.48 (m, 1H), number SR/S1/OC-20/2012). B. S. R acknowledges the CSIR,
7.44–7.38 (m, 2H), 7.37–7.29 (m, 3H). 13C NMR (100 MHz, New Delhi for the award of research fellowship.
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