Download PDF
Synthesis 2014; 46(02): 195-202
DOI: 10.1055/s-0033-1338563
paper
© Georg Thieme Verlag Stuttgart · New York

Catalytic C–H Activation of Arylacetylenes: A Fast Assembly of 3-(Arylethynyl)-3-hydroxyindolin-2-ones Using CuI/DBU

Mangilal Chouhan
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India   Email: vn74nr@yahoo.com
,
Kishna Ram Senwar
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India   Email: vn74nr@yahoo.com
,
Kapil Kumar
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India   Email: vn74nr@yahoo.com
,
Ratnesh Sharma
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India   Email: vn74nr@yahoo.com
,
Vipin A. Nair*
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India   Email: vn74nr@yahoo.com
› Author Affiliations
Further Information

Publication History

Received: 27 August 2013

Accepted after revision: 29 October 2013

Publication Date:
28 November 2013 (online)

 
 PDF Download Permissions and Reprints All articles of this category


Abstract

A highly efficient and atom-economic methodology has been developed for the synthesis of 3-(arylethynyl)-3-hydroxyindolin-2-ones from isatins by C–H activation of arylacetylenes using a catalytic quantity of copper(I) iodide (5 mol%) and DBU (20 mol%) at 25 °C, affording the products in excellent yields in very short reaction time (5 min).


#

Key words

catalysis - C–H activation - copper(I) iodide - arylalkyne addition - 3-hydroxyindolin-2-ones

The C–H bond activation of relatively inert organic compounds has been an area of the intense research and mechanistic studies.[1] It continues to attract the attention of synthetic chemists due to the challenges encountered in C–C bond formation in the synthesis of complex organic molecules.[2] An interesting example that has wide significance is the synthesis of propargylic alcohols[3] from metal acetylides via activation of the C–H bond of the terminal alkyne and subsequent addition to carbonyl substrates. These compounds are versatile building blocks for complex natural products.[4] The available reports for direct alkynylation of aldehydes or ketones include use of metal acetylides like alkynylmagnesium,[5] alkynyllithium,[5] boryl acetylide,[6] and zinc alkynilide.[7] Gold(I) was an effective catalyst in water for the three-component coupling reactions of α-oxyaldehydes, alkynes, and amines to afford propargylamines in good yields and moderate diastereoselectivities.[8] Cesium hydroxide monohydrate catalytically activates the C–H bond of alkynes to afford propargylic alcohols from aliphatic aldehydes or ketones.[9] Microwave-assisted copper(I)-catalyzed coupling of a ketone, an alkyne, and a primary amine, leading to secondary alkylpropargylamines is also reported.[10] Chiral variants of the reaction have been successfully attempted by reacting terminal alkynes with aldehydes in procedures involving catalytic quantities of zinc(II) metal and the chiral ligand N-methylephedrine with triethylamine.[11] The solvent-free alkynilide addition reaction furnishes chiral propargyl alcohols with good enantioselectivities.[12] Camphorsulfonamide–titanium complex was found to be another catalyst of choice for the enantioselective addition of phenylacetylene to aldehydes.[13] Addition reactions of phenylacetylene to isatin and its N-substituted derivatives are also well documented.[14] The direct alkynylation of isatins catalyzed by activation of alkyne C–H bond in water, mediated by N-heterocyclic carbene–silver complexes was efficient for the synthesis of 3-ethynyl-3-hydroxyindolin-2-ones;[14c] a rate enhancement by water was observed in the heterogeneous system. Despite the wide applicability, the available methods have limitations such as: pre-synthesis of metal acetylides; the use of substoichiometric (and not catalytic) amount of strongly basic reagents; air and moisture sensitivity; costly reagents, catalysts, and ligands; long reaction times; and moderate yields. These limitations provide sufficient scope for the development of newer catalysts.

Zoom Image
Figure 1 Efavirenz and a 3-alkynyl-3-hydroxy bioactive mimetic

Natural products containing the 3-substituted 3-hydroxyindolin-2-one scaffold, such as convolutamydines, diazonamide A, leptosin D, 3′-hydroxyglucoisatisin, witindolinone C, and dioxibrassinine have gained considerable attention because of their diverse biological activity.[15] In particular, 3-alkynyl-3-hydroxyindolin-2-ones showed excellent biological activity on Echinococcus multilocularis metacestodes.[5a] 3-(Cyclopropylethynyl)-3-hydroxy-5-methylindolin-2-one A was reported to exhibit activity greater than efavirenz against HIV-1 replication without significant cytotoxicity[16] (Figure [1]). Development of cost-effective and atom-economic approaches for the synthesis of these templates is highly desirable, which defines our keen interest.[17] Herein we report a highly efficient synthesis of 3-(arylethynyl)-3-hydroxyindolin-2-ones from isatins. Though the use of zinc complexes has demonstrated promising results in the synthesis of these scaffolds, the use of stoichiometric amounts of the reagents, long reaction times, and moderate yields are of concern.[14b] Our efforts resulted in a simple one-pot protocol employing catalytic amount of copper(I) iodide in combination with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) for in situ generation of copper alkynilide, and its subsequent reaction with isatin to afford 3-(arylethynyl)-3-hydroxyindolin-2-ones. The reagent system is highly convenient, both in terms of cost as well as in ease of handling. The products were obtained in high yields within a reaction time of five minutes.

To carry out a detailed investigation, a model reaction of phenylacetylene (2a) and 1-benzylisatin (1a) (Scheme [1]) was performed in presence of different copper salts and bases using toluene as the solvent at room temperature (25 °C) under a nitrogen atmosphere (Table [1]). Proton abstraction by the base from the alkyne terminus results in the formation of copper acetylide, which reacts with the isatin to afford 3-hydroxy-3-(phenylethynyl)indolin-2-one 3aa. From the different copper salts examined, it was inferred that copper(I) iodide provided maximum yields of 3aa in a short span of five minutes, at an optimum catalyst concentration of 5 mol% (entry 5) compared with copper(I) chloride and copper(I) bromide, which showed inferior results (entries 7 and 8). Examination of the effect of different bases on the outcome of the reaction indicated that 50 mol% of triethylamine and N,N-diisopropylethylamine afforded yields of 37% and 40%, respectively, after one hour (entries 2 and 3) while 50 mol% of DBU provided a maximum yield of 98% within five minutes (entry 5). In a separate study we observed that 20 mol% of DBU is sufficient to catalyze the reaction (entry 6).

Zoom Image
Scheme 1 One-pot alkynylation of isatin by C–H activation

Further, the effect of the solvents as a reaction parameter was also evaluated (Table [2]). In the case of polar protic solvents like ethanol and water (entries 4 and 5), the starting material remained as such even after two hours, while an improvement was observed with polar aprotic solvents (entries 1–3). Nonpolar solvents like toluene exhibited an enhancement in the reaction rate (entry 6), providing excellent yields of the desired product in a very short period of time. The reason for the high output in toluene could be attributed to the hydrophobic environment provided by the solvent which assists in the generation of the copper acetylide and drives its subsequent reaction with the electrophilic carbonyl carbon. The longer reaction time and low yield in polar aprotic solvent such as tetrahydrofuran, N,N-dimethylformamide, and acetonitrile might be due to coordination ability of these solvent molecules with the in situ generated nucleophile and stabilization of the polar transition state. A competing protonation of the generated nucleophile in polar protic solvents can be reasoned for the failure of the reaction in water and ethanol. In the absence of a nitrogen atmosphere the reaction was sluggish (8 h) and afforded only a moderate yield (55%). From these observations we inferred that reacting 1.0 equivalent of the N-benzylisatin 1a with 1.05 equivalents of phenylacetylene (2a), 0.05 equivalents of copper(I) iodide, 0.2 equivalents of 1,8-diazabicyclo[5.4.0]undec-7-ene in toluene at 25 °C under a nitrogen atmosphere would be the ideal conditions for the reaction. The reactions of isatins with a free NH group did not afford the desired products under the experimental conditions.

Table 1 Effect of Various Copper Catalysts on the Alkynylation of Isatinsa

Entry

Catalyst (mol%)

Base (mol%)

Time (min)

Yieldb (%)

 1

–

Et3N (50)

 60

trace

 2

CuI (10)

Et3N (50)

 60

37

 3

CuI (10)

DIPEA (50)

 60

40

 4

CuI (10)

DBU (50)

  5

98

 5

CuI (5)

DBU (50)

  5

97

 6

CuI (5)

DBU (20)

  5

97

 7

CuCl (10)

DBU (50)

 60

30

 8

CuBr (10)

DBU (50)

 60

65

 9

CuO (10)

DBU (50)

120

–c

10

Cu(OAc)2 (10)

DBU (50)

120

–c

a 1-Benzylisatin (1a, 1.0 equiv), phenylacetylene (2a, 1.05 equiv), toluene (2 mL), N2 atmosphere, 25 °C.

b Isolated yield.

c Not determined.

Table 2 Effect of Solvents on the Alkynylation of Isatinsa

Entry

Solvent

Time (min)

Yieldb (%)

1

THF

120

30

2

DMF

120

45

3

MeCN

120

25

4

EtOH

120

–c

5

H2O

120

–c

6

toluene

  5

98

a 1-Benzylisatin (1a, 1.0 equiv), phenylacetylene (2a, 1.05 equiv), CuI (5 mol%), DBU (20 mol%), N2 atmosphere, 25 °C.

b Isolated yield.

c Not determined.

Under the standardized conditions, the reaction was generalized on substituted arylacetylenes 2a–f and N-alkylisatins 1a–h to afford 3-(arylethynyl)-3-hydroxyindolin-2-one derivatives 3aa–ef in excellent yields (Table [3]). The operationally simple one-pot procedure, utilizes reactants without prior preparation and works well irrespective of the substituents on the arylacetylene. The scope of the reaction was also examined by carrying out the model reaction on a 10-gram scale, which afforded the product in good yield (85%), though the reaction took a longer time to go to completion (1 h). However, attempts to extend the reaction condition to simple aldehydes and unactivated ketones, as electrophiles, failed. Similarly, the reactions of N-alkylisatins with alkylacetylenes were also unsuccessful.

Table 3 Synthesis of 3-(Arylethynyl)-3-hydroxyindolin-2-onesa

Entry

R1

R2

R3

Product

Yielda (%)

 1

H

Bn

H

3aa

97

 2

F

Bn

H

3ba

94

 3

Cl

Bn

H

3ca

96

 4

Br

Bn

H

3da

97

 5

H

Me

H

3ea

98

 6

F

Me

H

3fa

95

 7

Cl

Me

H

3ga

97

 8

Br

Me

H

3ha

95

 9

H

Bn

4-Br

3ab

96

10

F

Bn

4-Br

3bb

97

11

Cl

Bn

4-Br

3cb

95

12

Br

Bn

4-Br

3db

96

13

H

Me

4-Br

3eb

97

14

F

Me

4-Br

3fb

94

15

Cl

Me

4-Br

3gb

96

16

Br

Me

4-Br

3hb

97

17

H

Bn

4-Me

3ac

96

18

F

Bn

4-Me

3bc

95

19

Cl

Bn

4-Me

3cc

97

20

Br

Bn

4-Me

3dc

96

21

H

Me

4-Me

3ec

98

22

F

Me

4-Me

3fc

95

23

Cl

Me

4-Me

3gc

96

24

Br

Me

4-Me

3hc

95

25

H

Bn

2-OMe

3ad

95

26

H

Me

2-OMe

3ed

93

27

H

Bn

2-CF3

3ae

96

28

H

Me

2-CF3

3ee

93

29

H

Bn

H

3af

95

30

H

Me

H

3ef

96

a Isatin 1 (1.0 equiv), arylacetylene 2 (1.05 equiv).

b Isolated yield.

Based on these observations, a plausible reaction mechanism for the product formation can be envisaged (Scheme [2]). It can fairly be assumed that initially copper(I) iodide coordinates with the arylacetylene weakening the terminal C–H bond. This facilitates the abstraction of the terminal proton by DBU and generates the copper acetylide nucleophile, which attacks the electrophilic carbonyl carbon to afford the addition product. Electrophilic activation by coordination between the metal center of the in situ generated copper acetylide and the carbonyl group of isa­tin can also be expected to account for the fast reaction kinetics.

Zoom Image
Scheme 2 Plausible mechanism

In conclusion, a one-pot, atom-economic methodology was developed for the syntheses of 3-(arylethynyl)-3-hydroxyindolin-2-ones by C–H activation of arylacetylenes using copper(I) iodide (5 mol%) and DBU (20 mol%) in toluene at 25 °C. The reaction afforded excellent yields of the products in very short reaction time (5 min). The procedure has advantages over the previously reported methods such as use of catalytic amount of the readily available and inexpensive reagents that could be handled easily, in situ generation of the copper arylacetylide, employing costly alkynes only in stoichiometric quantities and not in excess, and high reactivity with arylacetylenes bearing both electron-withdrawing and electron-donating groups.

1H and 13C NMR spectra were recorded at 400 and 100 MHz, respectively on a Bruker Avance DPX 400 (400 MHz) spectrometer in CDCl3 using TMS as the internal standard and the residual signal of the solvents. HRMS spectra were recorded on Bruker Maxix TOF spectrometer. The reactions were monitored using TLC silica gel 60 F254 (Merck). Evaporation of solvents was performed under reduced pressure. Melting points were recorded and uncorrected. All the starting isatins (isatin, 5-fluoroisatin, 5-chloroisatin, 5-bromoisatin), copper salts [CuCl, CuBr, CuI, Cu(OAc)2, CuO] and solvents (MeCN, DMF, THF, EtOH, toluene) were purchased from commercial sources and used as such without further purification.


#

1-Benzyl-3-hydroxy-3-(phenylethynyl)-1,3-dihydro-2H-indol-2-one (3aa); Typical Procedure

To a stirred mixture of 1-benzyl-1H-indole-2,3-dione (1a, 0.25 g, 1.05 mmol), CuI (0.01 g, 0.05 mmol, 0.05 equiv), and phenylacetylene (2a, 0.11 g, 1.11 mmol, 1.05 equiv) in anhyd toluene (2 mL), DBU (0.032 g, 0.21 mmol, 0.2 equiv) was added at 25 °C under a N2 atmosphere. Stirring was continued at this temperature until the starting material was completely consumed (TLC monitoring). After completion, the mixture was quenched with sat. aq NH4Cl (2 mL) and extracted with EtOAc (2 × 5 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated under reduced pressure to dryness. The crude product thus obtained was purified by column chromatography (activated silica gel, 60–120 mesh, hexane–EtOAc) to afford pure 3aa as a white solid; yield: 0.35 g (97%); mp 177–179 °C.

IR (KBr): 3292, 2839, 2223, 1707, 1616, 1494, 1466, 1456, 1375, 1271, 1123, 1071, 1018, 976, 760, 749, 625, 600, 494 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.88 (br s, 1 H), 4.93 (s, 2 H), 6.72 (d, J = 7.8 Hz, 1 H), 7.12 (dt, J = 0.7, 7.6 Hz, 1 H), 7.22–7.35 (m, 9 H), 7.44–7.46 (m, 2 H), 7.62 (dd, J = 0.8, 7.4 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 44.1, 69.6, 85.5, 86.6, 110.0, 121.6, 123.8, 124.8, 127.2, 127.8, 128.2, 128.9, 129.0, 129.1, 130.4, 132.1, 135.0, 142.1, 174.2.

HRMS (ESI): m/z [M + Na]+ calcd for C23H17NO2Na: 362.1157; found: 362.1157.


#

1-Benzyl-5-fluoro-3-hydroxy-3-(phenylethynyl)-1,3-dihydro-2H-indol-2-one (3ba)

White solid; yield: 0.33 g (94%); mp 156–158 °C.

IR (KBr): 3377, 3055, 2936, 2233, 1883, 1701, 1610, 1491, 1349, 1262, 1106, 1049, 825, 816, 684, 600, 477 cm–1.

1H NMR (400 MHz, CDCl3): δ = 4.16 (br s, 1 H), 4.92 (s, 2 H), 6.61–6.65 (m, 1 H), 6.92–6.97 (m, 1 H), 7.26–7.38 (m, 9 H), 7.44–7.46 (m, 2 H).

13C NMR (100 MHz, CDCl3): δ = 44.3, 69.7, 84.9, 87.0, 110.6, 110.7, 112.8, 113.1, 116.6, 116.8, 121.4, 127.1, 127.9, 128.3, 129.0, 130.4, 132.1, 134.7, 138.0, 158.5, 160.9, 174.0.

HRMS (ESI): m/z [M + Na]+ calcd for C23H16FNO2Na: 380.1063; found: 380.1061.


#

1-Benzyl-5-chloro-3-hydroxy-3-(phenylethynyl)-1,3-dihydro-2H-indol-2-one (3ca)

White solid; yield: 0.33 g (96%); mp 176–178 °C.

IR (KBr): 3308, 2219, 1715, 1612, 1488, 1435, 1350, 1171, 1122, 1077, 1030, 986, 881, 811, 760, 740, 722, 691, 606 cm–1.

1H NMR (400 MHz, CDCl3): δ = 4.12 (br s, 1 H), 4.91 (s, 2 H), 6.62 (d, J = 8.4 Hz, 1 H), 7.20 (dd, J = 2.2, 8.4 Hz, 1 H), 7.25–7.36 (m, 8 H), 7.44–7.47 (m, 2 H), 7.59 (d, J = 2.1 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 44.2, 69.5, 84.8, 87.1, 111.0, 121.3, 125.4, 127.1, 128.0, 128.2, 128.3, 129.0, 129.2, 130.3, 130.4, 132.1, 134.6, 140.6, 173.8.

HRMS (ESI): m/z [M + Na]+ calcd for C23H16ClNO2Na: 396.0767; found: 396.0767.


#

1-Benzyl-5-bromo-3-hydroxy-3-(phenylethynyl)-1,3-dihydro-2H-indol-2-one (3da)

White solid; yield: 0.32 g (97%); mp 188–190 °C.

IR (KBr): 3303, 3081, 3066, 2927, 2228, 1925, 1705, 1619, 1494, 1348, 1262, 1143, 1064, 995, 882, 781, 636, 533 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.94 (br s, 1 H), 4.90 (s, 2 H), 6.58 (dd, J = 3.2, 8.3 Hz, 1 H), 7.28–7.37 (m, 9 H), 7.46 (d, J = 7.6 Hz, 2 H), 7.73 (s, 1 H).

13C NMR (100 MHz, CDCl3): δ = 44.2, 69.4, 84.7, 87.2, 111.4, 116.4, 121.3, 127.1, 128.0, 128.1, 128.3, 129.0, 129.2, 130.7, 132.1, 133.2, 134.5, 141.1, 173.6.

HRMS (ESI): m/z [M + Na]+ calcd for C23H16BrNO2Na: 440.0262; found: 440.0258.


#

3-Hydroxy-1-methyl-3-(phenylethynyl)-1,3-dihydro-2H-indol-2-one (3ea)

White solid; yield: 0.40 g (98%); mp 164–166 °C.

IR (KBr): 3285, 2917, 2218, 1706, 1614, 1464, 1376, 1178, 1068, 982, 759, 694, 641 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 3.84 (br s, 1 H), 6.86 (d, J = 7.8 Hz, 1 H), 7.16 (t, J = 7.5 Hz, 1 H), 7.24–7.33 (m, 3 H), 7.36–7.44 (m, 3 H), 7.62 (d, J = 7.4 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.6, 69.5, 85.4, 86.4, 108.9, 121.6, 123.8, 124.7, 128.2, 128.8, 129.0, 130.5, 132.1, 143.1, 173.9.

HRMS (ESI): m/z [M + Na]+ calcd for C17H13NO2Na: 286.0844; found: 286.0863.


#

5-Fluoro-3-hydroxy-1-methyl-3-(phenylethynyl)-1,3-dihydro-2H-indol-2-one (3fa)

White solid; yield: 0.37 g (95%); mp 175–177 °C.

IR (KBr): 3315, 2230, 1715, 1613, 1488, 1435, 1350, 1171, 1122, 1077, 986, 881, 811, 760, 740, 691, 606 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.81 (br s, 1 H), 6.79 (dd, J = 4.0, 8.5 Hz, 1 H), 7.09 (dt, J = 2.6, 9.0 Hz, 1 H), 7.28–7.37 (m, 4 H), 7.44 (dd, J = 0.2, 7.4 Hz, 2 H).

13C NMR (100 MHz, CDCl3): δ = 26.8, 69.5, 84.8, 86.8, 109.5, 109.6, 112.8, 113.1, 116.7, 116.9, 121.3, 128.3, 129.2, 130.1, 130.2, 132.1, 139.0, 158.5, 161.0, 173.6.

HRMS (ESI): m/z [M + Na]+ calcd for C17H12FNO2Na: 304.0750; found: 304.0774.


#

5-Chloro-3-hydroxy-1-methyl-3-(phenylethynyl)-1,3-dihydro-2H-indol-2-one (3ga)

White solid; yield: 0.37 g (97%); mp 190–192 °C.

IR (KBr): 3292, 2225, 1706, 1498, 1362, 1263, 1096, 995, 879, 813, 784, 760, 690 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.79 (br s, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 7.28–7.37 (m, 4 H), 7.44 (d, J = 6.6 Hz, 2 H), 7.59 (s, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.8, 69.3, 84.7, 86.9, 109.9, 121.2, 125.3, 128.3, 129.1, 129.2, 130.2, 130.4, 132.1, 141.6, 173.5.

HRMS (ESI): m/z [M + Na]+ calcd for C17H12ClNO2Na: 320.0454; found: 320.0450.


#

5-Bromo-3-hydroxy-1-methyl-3-(phenylethynyl)-1,3-dihydro-2H-indol-2-one (3ha)

White solid; yield: 0.34 g (95%); mp 188–190 °C.

IR (KBr): 3293, 2936, 2223, 1707, 1615, 1492, 1375, 1270, 1171, 1071, 976, 814, 761, 700, 647, 494 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.21 (s, 3 H), 3.99 (br s, 1 H), 6.72 (d, J = 8.3 Hz, 1 H), 7.24–7.34 (m, 3 H), 7.42–7.44 (m, 2 H), 7.49 (dd, J = 2.0, 8.3 Hz, 1 H), 7.72 (d, J = 2.0 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.7, 69.3, 84.8, 86.9, 110.3, 116.3, 121.3, 128.0, 128.2, 129.2, 130.7, 132.1, 133.3, 142.1, 173.5.

HRMS (ESI): m/z [M + Na]+ calcd for C17H12BrNO2Na: 363.9949; found: 363.9952.


#

1-Benzyl-3-[(4-bromophenyl)ethynyl]-3-hydroxy-1,3-dihydro-2H-indol-2-one (3ab)

White solid; yield: 0.42 g (96%); mp 180–182 °C.

IR (KBr): 3421, 2923, 1615, 1376, 1178, 696 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.64 (br s, 1 H), 4.95 (s, 2 H), 6.75 (d, J = 8.0 Hz, 1 H), 7.14 (t, J = 7.4 Hz, 1 H), 7.26–7.34 (m, 8 H), 7.45 (d, J = 8.2 Hz, 2 H), 7.62 (d, J = 7.2 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 44.1, 69.6, 85.5, 86.6, 110.0, 120.5, 123.5, 123.8, 124.8, 127.2, 127.9, 128.6, 128.9, 130.5, 131.6, 133.5, 134.9, 142.2, 173.9.

HRMS (ESI ): m/z [M + Na]+ calcd for C23H16BrNO2Na: 440.0262; found: 440.0256.


#

1-Benzyl-3-[(4-bromophenyl)ethynyl]-5-fluoro-3-hydroxy-1,3-dihydro-2H-indol-2-one (3bb)

Pale brown solid; yield: 0.42 g (97%); mp 178–180 °C.

IR (KBr): 3304, 3066, 2228, 1705, 1620, 1494, 1347, 1262, 1176, 1143, 1011, 882, 810, 726, 696, 636, 532 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.94 (br s, 1 H), 4.91 (s, 2 H), 6.64 (dd, J = 4.0, 4.6 Hz, 1 H), 6.95 (dt, J = 2.6, 8.9 Hz, 1 H), 7.27–7.38 (m, 8 H), 7.42–7.45 (m, 2 H).

13C NMR (100 MHz, CDCl3): δ = 44.3, 69.6, 85.9, 86.0, 110.7, 110.8, 112.9, 113.1, 116.8, 117.0, 120.3, 123.7, 127.1, 128.0, 129.0, 131.6, 133.5, 134.6, 138.0, 158.5, 160.9, 173.8.

HRMS (ESI): m/z [M + Na]+ calcd for C23H15BrFNO2Na: 458.0168; found: 458.0171.


#

1-Benzyl-3-[(4-bromophenyl)ethynyl]-5-chloro-3-hydroxy-1,3-dihydro-2H-indol-2-one (3cb)

White solid; yield: 0.40 g (95%); mp 181–182 °C.

IR (KBr): 3418, 2225, 1730, 1703, 1609, 1487, 1329, 1168, 1126, 983, 823, 692, 622 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.65 (br s, 1 H), 4.91 (d, J = 2.1 Hz, 2 H), 6.64 (d, J = 8.4 Hz, 1 H), 7.22 (dd, J = 2.2, 8.4 Hz, 1 H), 7.29–7.35 (m, 7 H), 7.44–7.47 (m, 2 H), 7.58 (d, J = 2.1 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 44.3, 69.4, 86.0, 90.7, 111.0, 120.2, 123.8, 125.4, 127.1, 128.0, 129.0, 129.3, 130.0, 130.4, 131.6, 133.5, 134.5, 140.6, 173.5.

HRMS (ESI): m/z [M + Na]+ calcd for C23H15BrClNO2Na: 473.9872; found: 473.9898.


#

1-Benzyl-5-bromo-3-[(4-bromophenyl)ethynyl]-3-hydroxy-1,3-dihydro-2H-indol-2-one (3db)

Pale brown solid; yield: 0.38 g (96%); mp 189–191 °C.

IR (KBr): 3302, 2225, 1705, 1613, 1580, 1462, 1373, 1201, 1087, 1000, 781, 747, 696, 628, 609, 483 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.64 (br s, 1 H), 4.91 (s, 2 H), 6.59 (d, J = 8.2 Hz, 1 H), 7.26–7.38 (m, 8 H), 7.45 (d, J = 7.3 Hz, 2 H), 7.71 (s, 1 H).

13C NMR (100 MHz, CDCl3): δ = 44.2, 69.3, 85.8, 87.8, 111.5, 116.4, 123.8, 125.6, 127.1, 128.0, 128.1, 129.0, 130.3, 131.7, 133.3, 133.5, 134.4, 141.2, 173.5.

HRMS (ESI): m/z [M + Na]+ calcd for C23H15Br2NO2Na: 517.9367; found: 517.9401.


#

3-[(4-Bromophenyl)ethynyl]-3-hydroxy-1-methyl-1,3-dihydro-2H-indol-2-one (3eb)

White solid; yield: 0.52 g (97%); mp 176–177 °C.

IR (KBr): 3313, 2230, 1707, 1607, 1492, 1461, 1350, 1261, 1178, 1142, 1105, 1050, 994, 956, 872, 815, 785, 683, 605, 531, 471 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.98 (br s, 1 H), 6.86 (d, J = 7.8 Hz, 1 H), 7.17 (dt, J = 0.8, 7.6 Hz, 1 H), 7.26–7.29 (m, 2 H), 7.36–7.41 (m, 3 H), 7.60 (dd, J = 0.7, 7.3 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.7, 69.5, 85.2, 86.6, 108.9, 120.5, 123.4, 123.8, 124.7, 128.6, 130.6, 131.5, 133.5, 143.0, 173.8.

HRMS (ESI): m/z [M + Na]+ calcd for C17H12BrNO2Na: 363.9949; found: 363.9412.


#

3-[(4-Bromophenyl)ethynyl]-5-fluoro-3-hydroxy-1-methyl-1,3-dihydro-2H-indol-2-one (3fb)

White solid; yield: 0.47 g (94%); mp 165–167 °C.

IR (KBr): 3274, 2940, 2229, 1713, 1621, 1497, 1362, 1263, 1147, 1096, 996, 872, 813, 785, 698, 634, 555, 531 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.95 (br s, 1 H), 6.78–6.81 (m, 1 H), 7.07–7.12 (m, 1 H), 7.29 (d, J = 13.7 Hz, 2 H), 7.32–7.37 (m, 1 H), 7.42 (d, J = 8.5 Hz, 2 H).

13C NMR (100 MHz, CDCl3): δ = 26.8, 69.5, 85.7, 86.0, 109.6, 109.7, 112.9, 113.1, 116.8, 117.0, 120.3, 123.6, 131.6, 133.5, 138.9, 173.6.

HRMS (ESI): m/z [M + Na]+ calcd for C17H11BrFNO2Na: 381.9855; found: 381.9851.


#

3-[(4-Bromophenyl)ethynyl]-5-chloro-3-hydroxy-1-methyl-1,3-dihydro-2H-indol-2-one (3gb)

White solid; yield: 0.46 g (96%); mp 212–214 °C.

IR (KBr): 3313, 2225, 1730, 1703, 1609, 1487, 1329, 1253, 1168, 1079, 983, 822, 692 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 3.57 (br s, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 7.31 (d, J = 8.3 Hz, 2 H), 7.36 (d, J = 8.3 Hz, 1 H), 7.44 (d, J = 8.1 Hz, 2 H), 7.57 (s, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.8, 68.3, 86.5, 88.7, 109.8, 116.0, 120.4, 122.8, 128.6, 130.1, 131.7, 132.6, 133.1, 141.6, 173.1.

HRMS (ESI): m/z [M + Na]+ calcd for C17H11BrClNO2Na: 397.9559; found: 397.9559.


#

5-Bromo-3-[(4-bromophenyl)ethynyl]-3-hydroxy-1-methyl-1,3-dihydro-2H-indol-2-one (3hb)

White solid; yield: 0.43 g (97%); mp 218–220 °C.

IR (KBr): 3381, 2235, 1700, 1607, 1488, 1349, 1259, 1105, 1049, 826, 816, 714, 530 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.84 (br s, 1 H), 6.75 (d, J = 8.3 Hz, 1 H), 7.30 (d, J = 8.6 Hz, 2 H), 7.43 (d, J = 8.5 Hz, 2 H), 7.51 (dd, J = 2.0, 8.3 Hz, 1 H), 7.70 (d, J = 2.0 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.8, 69.2, 85.8, 85.9, 110.4, 116.4, 120.2, 123.7, 128.0, 130.3, 131.6, 133.4, 133.5, 142.1, 173.2.

HRMS (ESI): m/z [M + Na]+ calcd for C17H11Br2NO2Na: 441.9054; found: 441.9050.


#

1-Benzyl-3-hydroxy-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-2-one (3ac)

White solid; yield: 0.36 g (96%); mp 202–203 °C.

IR (KBr): 3317, 2937, 2221, 1708, 1612, 1492, 1457, 1267, 1170, 1082, 874, 762, 694, 615, 480 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.78 (br s, 1 H), 4.92 (s, 2 H), 6.71 (d, J = 7.8 Hz, 1 H), 7.08–7.13 (m, 3 H), 7.22–7.35 (m, 8 H), 7.61 (dd, J = 0.9, 7.4 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 21.5, 44.1, 69.6, 84.8, 86.8, 109.9, 118.5, 123.7, 124.8, 127.2, 127.8, 128.9, 129.0, 129.0, 130.3, 132.0, 135.0, 139.3, 142.1, 174.2.

HRMS (ESI): m/z [M + Na]+ calcd for C24H19NO2Na: 376.1313; found: 376.1311.


#

1-Benzyl-5-fluoro-3-hydroxy-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-2-one (3bc)

White solid; yield: 0.35 g (95%); mp 182–184 °C.

IR (KBr): 3314, 2223, 1708, 1616, 1493, 1350, 1261, 1177, 1083, 994, 871, 813, 785, 721, 685, 605, 556, 530 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H), 3.84 (br s, 1 H), 4.91 (s, 2 H), 6.62 (dd, J = 4.0, 8.6 Hz, 1 H), 6.93 (dt, J = 2.6, 8.9 Hz, 1 H), 7.10 (d, J = 7.8 Hz, 2 H), 7.26–7.37 (m, 8 H).

13C NMR (100 MHz, CDCl3): δ = 21.5, 44.2, 69.6, 84.2, 87.3, 110.6, 110.7, 112.8, 113.1, 116.5, 116.8, 118.2, 127.1, 129.1, 130.5, 132.0, 134.7, 138.0, 139.5, 160.9, 174.0.

HRMS (ESI): m/z [M + Na]+ calcd for C24H18FNO2Na: 394.1219; found: 394.1219.


#

1-Benzyl-5-chloro-3-hydroxy-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-2-one (3cc)

White solid; yield: 0.35 g (97%); mp 199–200 °C.

IR (KBr): 3302, 3030, 2933, 2221, 1708, 1614, 1489, 1366, 1345, 1271, 1169, 1121, 1077, 985, 816, 683, 642, 532, 475 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.35 (s, 3 H), 3.70 (br s, 1 H), 4.91 (s, 2 H), 6.62 (d, J = 8.3 Hz, 1 H), 7.11 (d, J = 7.2 Hz, 2 H), 7.20 (d, J = 8.16 Hz, 1 H), 7.19–7.37 (m, 7 H), 7.58 (s, 1 H).

13C NMR (100 MHz, CDCl3): δ = 21.5, 44.2, 69.5, 84.1, 87.4, 110.9, 118.2, 125.3, 127.1, 128.0, 129.0, 129.1, 129.2, 130.2, 130.4, 132.0, 134.6, 139.5, 140.6, 173.3.

HRMS (ESI): m/z [M + Na]+ calcd for C24H18ClNO2Na: 410.0924; found: 410.0919.


#

1-Benzyl-5-bromo-3-hydroxy-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-2-one (3dc)

White solid; yield: 0.33 g (96%); mp 200–202 °C.

IR (KBr): 3303, 3066, 2927, 2228, 1926, 1705, 1620, 1494, 1348, 1262, 1176, 1143, 1064, 957, 882, 810, 726, 695, 636, 603, 533, 495 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H), 3.81 (br s, 1 H), 4.90 (s, 2 H), 6.57 (d, J = 8.4 Hz, 1 H), 7.11 (d, J = 7.9 Hz, 2 H), 7.25–7.36 (m, 8 H), 7.72 (d, J = 2.0 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 21.5, 44.2, 69.4, 84.1, 87.4, 111.4, 116.4, 118.2, 127.1, 127.9, 128.1, 129.0, 129.1, 130.8, 132.0, 133.1, 134.6, 139.5, 141.1, 173.7.

HRMS (ESI): m/z [M + Na]+ calcd for C24H18BrNO2Na: 454.0419; found: 454.0414.


#

3-Hydroxy-1-methyl-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-2-one (3ec)

White solid; yield: 0.42 g (98%); mp 150–152 °C.

IR (KBr): 3745, 3315, 3031, 2920, 2216, 1909, 1709, 1611, 1490, 1370, 1352, 1195, 1132, 1093, 993, 821, 754, 692, 662, 490, 481 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H), 3.25 (s, 3 H), 3.58 (br s, 1 H), 6.88 (d, J = 7.7 Hz, 1 H), 7.10 (d, J = 7.2 Hz, 2 H), 7.17 (t, J = 7.5 Hz, 1 H), 7.33–7.41 (m, 3 H), 7.62 (d, J = 7.1 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 21.5, 26.6, 69.5, 84.8, 86.6, 108.8, 118.5, 123.7, 124.7, 128.9, 129.0, 130.5, 132.0, 139.3, 143.1, 173.9.

HRMS (ESI): m/z [M + Na]+ calcd for C18H15NO2Na: 300.1000; found: 300.1009.


#

5-Fluoro-3-hydroxy-1-methyl-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-2-one (3fc)

White solid; yield: 0.39 g (95%); mp 134–136 °C.

IR (KBr): 3736, 3315, 2217, 1708, 1611, 1469, 1370, 1255, 1196, 1093, 993, 937, 821, 754, 693, 582, 532, 482 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.23 (s, 3 H), 3.80 (br s, 1 H), 6.78–6.80 (m, 1 H), 7.09 (d, J = 7.6 Hz, 3 H), 7.19–7.36 (m, 3 H).

13C NMR (100 MHz, CDCl3): δ = 21.5, 26.8, 69.6, 84.2, 87.0, 109.4, 112.8, 113.0, 116.6, 118.2, 129.0, 130.3, 132.0, 139.5, 158.5, 160.9, 173.7.

HRMS (ESI): m/z [M + Na]+ calcd for C18H14FNO2Na: 318.0906; found: 318.0908.


#

5-Chloro-3-hydroxy-1-methyl-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-2-one (3gc)

White solid; yield: 0.38 g (96%); mp 199–200 °C.

IR (KBr): 3377, 3055, 2936, 2233, 1699, 1610, 1491, 1349, 1262, 1106, 1049, 883, 824, 816, 731, 684, 545, 477 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.23 (s, 3 H), 3.62 (br s, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 7.09 (d, J = 7.9 Hz, 2 H), 7.32–7.36 (m, 3 H), 7.58 (d, J = 2.1 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 21.5, 26.8, 69.4, 84.0, 87.2, 109.8, 118.1, 125.3, 129.0, 129.1, 130.3, 130.4, 132.0, 139.5, 141.6, 173.5.

HRMS (ESI): m/z [M + Na]+ calcd for C18H14ClNO2Na: 334.0611; found: 334.0610.


#

5-Bromo-3-hydroxy-1-methyl-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-2-one (3hc)

White solid; yield: 0.35 g (95%); mp 216–218 °C.

IR (KBr): 3315, 3053, 2922, 2230, 1705, 1607, 1493, 1350, 1261, 1178, 1105, 1050, 815, 785, 683, 605, 531, 473 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.22 (s, 3 H), 3.72 (br s, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 7.09 (d, J = 7.6 Hz, 2 H), 7.33 (d, J = 7.4 Hz, 2 H), 7.50 (d, J = 8.2 Hz, 1 H), 7.71 (s, 1 H).

13C NMR (100 MHz, CDCl3): δ = 21.5, 26.7, 69.3, 84.1, 87.2, 110.3, 116.3, 118.2, 128.0, 129.0, 130.7, 132.0, 133.2, 139.5, 142.1, 173.5.

HRMS (ESI): m/z [M + Na]+ calcd for C18H14BrNO2Na: 378.0106; found: 378.0101.


#

1-Benzyl-3-hydroxy-3-[(2-methoxyphenyl)ethynyl]-1,3-dihydro-2H-indol-2-one (3ad)

White solid; yield: 0.37 g (95%); mp 184–187 °C.

IR (KBr): 3737, 3293, 3060, 2223, 1707, 1616, 1492, 1466, 1348, 1271, 1171, 1018, 976, 813, 760, 748, 701, 651, 547, 494 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.81 (br s, 1 H), 3.85 (s, 3 H), 4.93 (s, 2 H), 6.70 (d, J = 7.8 Hz, 1 H), 6.84–6.89 (m, 2 H), 7.09–7.27 (m, 2 H), 7.28–7.41 (m, 7 H), 7.62–7.64 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 44.1, 55.8, 69.8, 83.2, 89.4, 109.8, 110.7, 110.8, 120.3, 123.7, 124.9, 127.2, 127.8, 128.8, 128.9, 130.3, 130.6, 133.9, 135.1, 142.2, 160.6, 174.2.

HRMS (ESI): m/z [M + Na]+ calcd for C24H19NO3Na: 392.1263; found: 392.1268.


#

3-Hydroxy-3-[(2-methoxyphenyl)ethynyl]-1-methyl-1,3-dihydro-2H-indol-2-one (3ed)

White solid; yield: 0.42 g (93%); mp 214–216 °C.

IR (KBr): 3377, 2233, 1701, 1610, 1491, 1349, 1136, 1106, 1049, 883, 816, 684, 545, 530, 477 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 3.76 (br s, 1 H), 3.85 (s, 3 H), 6.83–6.88 (m, 3 H), 7.13–7.18 (m, 1 H), 7.29–7.39 (m, 3 H), 7.61–7.63 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.6, 55.8, 69.7, 83.0, 89.4, 108.8, 110.7, 110.8, 120.3, 123.7, 124.8, 128.9, 130.5, 130.6, 133.9, 143.2, 160.5, 173.9.

HRMS (ESI): m/z [M + Na]+ calcd for C18H15NO3Na: 316.0950; found: 316.0956.


#

1-Benzyl-3-hydroxy-3-[(2-(trifluoromethyl)phenyl)ethynyl]-1,3-dihydro-2H-indol-2-one (3ae)

White solid; yield: 0.41 g (96%); mp 155–157 °C.

IR (KBr): 3128, 2953, 2822, 1909, 1682, 1598, 1361, 1222, 1137, 1012, 997, 961, 918, 829, 740, 614, 544, 498, 465 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.88 (br s, 1 H), 4.86 (d, J = 15.8 Hz, 1 H), 5.00 (d, J = 15.8 Hz, 1 H), 6.72 (d, J = 7.8 Hz, 1 H), 7.10–7.14 (m, 1 H), 7.23–7.34 (m, 6 H), 7.40–7.48 (m, 2 H), 7.60–7.64 (m, 3 H).

13C NMR (100 MHz, CDCl3): δ = 44.1, 69.6, 82.3, 90.9, 109.9, 123.8, 124.9, 125.8, 125.9, 127.1, 127.8, 128.3, 128.9, 128.9, 130.5, 131.4, 132.3, 134.3, 134.9, 142.1, 173.7.

HRMS (ESI): m/z [M + Na]+ calcd for C24H16F3NO2Na: 430.1031; found: 430.1035.


#

3-Hydroxy-1-methyl-3-[(2-(trifluoromethyl)phenyl)ethynyl]-1,3-dihydro-2H-indol-2-one (3ee)

White solid; yield: 0.48 g (93%); mp 175–177 °C.

IR (KBr): 3292, 2227, 1706, 1611, 1291, 1473, 1376, 1318, 1207, 1166, 1106, 1030, 997, 936, 753, 605, 492 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 3.80 (br s, 1 H), 6.86 (d, J = 7.8 Hz, 1 H), 7.15–7.19 (m, 1 H), 7.37–7.47 (m, 3 H), 7.58–7.63 (m, 3 H).

13C NMR (100 MHz, CDCl3): δ = 26.7, 69.5, 82.1, 90.9, 108.9, 123.8, 124.9, 125.8, 125.9, 128.3, 128.9, 130.7, 131.4, 132.4, 134.3, 139.1, 143.1, 173.4.

HRMS (ESI): m/z [M + Na]+ calcd for C18H12F3NO2Na: 354.0718; found: 354.0718.


#

1-Benzyl-3-hydroxy-3-(pyridin-2-ylethynyl)-1,3-dihydro-2H-indol-2-one (3af)

White solid; yield: 0.34 g (95%); mp 166–168 °C.

IR (KBr): 3736, 2230, 1707, 1608, 1491, 1351, 1216, 1178, 1142, 1105, 1050, 995, 872, 815, 785, 684, 605, 531, 474 cm–1.

1H NMR (400 MHz, CDCl3): δ = 4.93 (s, 2 H), 6.02 (br s, 1 H), 6.70 (d, J = 7.8 Hz, 1 H), 7.08–7.32 (m, 8 H), 7.42 (d, J = 7.8 Hz, 1 H), 7.61 (t, J = 7.7 Hz, 1 H), 7.73 (d, J = 7.4 Hz, 1 H), 8.58 (d, J = 4.2 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 44.2, 69.5, 85.0, 86.2, 109.8, 123.5, 123.9, 125.2, 127.2, 127.6, 127.7, 127.8, 128.9, 130.4, 135.1, 136.4, 141.9, 142.2, 149.8, 174.0.

HRMS (ESI): m/z [M + Na]+ calcd for C22H16N2O2Na: 363.1109; found: 363.1122.


#

3-Hydroxy-1-methyl-3-(pyridin-2-ylethynyl)-1,3-dihydro-2H-indol-2-one (3ef)

White solid; yield: 0.40 g (96%); mp 175–177 °C.

IR (KBr): 3303, 2225, 1705, 1614, 1462, 1373, 1271, 1201, 1089, 1000, 939, 858, 782, 747, 696, 628, 609, 538, 494, 484 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 5.19 (br s, 1 H), 6.84 (d, J = 7.8 Hz, 1 H), 7.12–7.16 (m, 1 H), 7.22–7.26 (m, 1 H), 7.34–7.38 (m, 1 H), 7.43 (d, J = 7.8 Hz, 1 H), 7.60–7.64 (m, 1 H), 7.69 (d, J = 7.4 Hz, 1 H), 8.55 (d, J = 4.7 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.7, 69.4, 84.9, 85.9, 108.8, 123.5, 123.8, 125.0, 127.5, 128.6, 130.6, 136.3, 141.9, 143.1, 149.9, 173.6.

HRMS (ESI): m/z [M + Na]+ calcd for C16H12N2O2Na: 287.0796; found: 287.0796.


#
#

Acknowledgment

Research funding from the National Institute of Pharmaceutical Education and Research (NIPER), and the Department of Science and Technology (DST), Government of India are gratefully acknowledged.

Supporting Information

    for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synthesis. Included are scanned spectra (IR, 1H NMR, 13C NMR and HRMS).
  • Supporting Information


   Permissions and Reprints All articles of this category
Zoom Image
Figure 1 Efavirenz and a 3-alkynyl-3-hydroxy bioactive mimetic
Zoom Image
Scheme 1 One-pot alkynylation of isatin by C–H activation
Zoom Image
Scheme 2 Plausible mechanism