“On water” highly atom economical and rapid synthesis of a novel class of 3-hydroxy-2-oxindole scaffolds under a catalyst-free and column chromatography-free protocol at room temperature

Abstract

An “on water” highly atom economical and rapid protocol has been developed for the synthesis of a novel class of 3-(2-pyrazolin-5-one) substituted, 3-hydroxy-2-oxindole scaffolds under catalyst-free and column chromatography-free conditions at rt. The generality of the method has been demonstrated by screening a series of isatin electrophiles as well as 2-pyrazolin-5-one derivatives. The developed method is a good example of green synthesis in which straightforward synthesis of a medicinally important 3-hydroxy-2-oxindole framework is executed by employing very mild, simple and handy procedures from readily available starting materials.

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Introduction

In the current scenario of chemical synthesis around the world, the term “green chemistry” coined by P. T. Anastas is well acknowledged in both academia and the chemical industry.¹ The world-wide synthetic community is already aware of an urgency to development of green chemistry processes, where non-toxic substances are used and the generation of waste can be avoided. Green synthesis protocols not only provide essential atom economy, energy savings, waste reduction, easy workup but also avoid hazardous chemicals.² Recently, the development of green protocols for the synthesis of highly functionalized motifs having medicinal value has emerged as an attractive area of research.³ However a question that exists is how far the green synthesis protocol could be developed to benefit the synthesis of biologically important molecules.

To speak of bioactive molecules, 3-substituted 3-hydroxy-2-oxindole displays a diverse array of natural products as well as pharmaceutically important compounds which possesses a wide range of biological activities.^4,5 Selective representative examples are depicted in Fig. 1. Due to such distinction, 3-substituted-3-hydroxy-2-oxindole framework remains an intensively investigated synthetic target.⁶ Likewise, pyrazolone is pharmaceutically important scaffolds and potential chemotherapeutic agents from the medicinal chemistry point of view possessing imperative biochemical properties.⁷ Representative examples of compound containing pyrazolone framework include remogliflozin etabonate, phenazone, propyphenazone, ampyrone, edaravone and metamizole.^7,8

Fig. 1 Selected representative examples of natural products and pharmaceuticals possessing 3-substituted-3-hydroxy-2-oxidole and pyrazolone structural framework.

The detailed structure–activity relationship studies on3-hydroxy-2-oxindole framework has shown that the biological effects of these compounds are known to vary with the substituent pattern at the C3 position of oxindoles.^4e In this context, we envision the C3 substituted molecular scaffold which assimilates 3-hydroxy-2-oxindole as well as pyrazolone framework which might integrate properties of both, and the synergism of both the heterocyclic moieties in a single nucleus may result in the formation of some worthwhile molecules from a biological point of view. Despite the prominence of 3-hydroxy-2-oxindole as well as pyrazolone framework in medicinal chemistry, there is no report on the synthesis of molecular scaffold possessing 3-pyrazolone substituted, 3-hydroxy-2-oxindole framework in the literature to date.

Recently pyrazolones have been explored as a nucleophilic donor in the construction of diversely functionalised heterocyclic scaffolds.⁹ Surprisingly, investigations on pyrazolones as nucleophilic donors with isatin electrophiles to afford 3-pyrazolone substituted 3-hydroxy-2-oxindole framework remained totally unexplored.^9p–v In this context and in continuation of our research work¹⁰ on synthesis of 3-substituted 3-hydroxy-2-oxindoles framework, we envisioned that the reaction between isatin and pyrazolone might be readily proceed to afford 3-pyrazolone substituted 3-hydroxy-2-oxindole structural framework (Scheme 1) without the use of any catalyst under certain appropriate reaction conditions due to the fact that the highly reactive β-carbonyl group of isatin is much susceptible to nucleophilic attack.¹¹ We herein wish to report “on water” novel, rapid, atom economical, catalyst-free, and column chromatography-free protocol for synthesis of 3-pyrazolone substituted 3-hydroxy-2-oxindole structural motif at room temperature. We believe that the developed method is one of the good example of an green synthesis protocol in which rapid synthesis of a novel class of medicinally important 3-hydroxy-2-oxindole molecular framework is achieved in quantitative yield using water under catalyst-free and column chromatography-free reaction condition.

Scheme 1 Envisioned synthesis of 3-pyrazolone substituted 3-hydroxy-2-oxindole structural framework.

Results and discussion

As we envisioned the reaction under catalyst-free¹² condition, we intended to begin our study using polar solvents. In this context, initially we performed the reaction of isatin 1a with 3-methyl-2-pyrazolin-5-one 2a without any added catalyst in slightly basic polar aprotic solvents like DMF. We were delighted to find that the reaction proceeds under this reaction condition gives 82% conversion of the desired product in 1 h (entry 1, Table 1). However cumbersome aqueous work-up, extraction and column chromatographic purification was found mandatory to get pure product due to which there was a substantial decrease in the yield of isolated product. Similar problem was occurred when we employed DMSO as solvent in the above reaction (entry 2, Table 1). Results with other solvents like CH₃CN, THF, MeOH and EtOH were also not much impressive (Table 1, entry 3–6 respectively). We observed that the solvent polarity has an important role in this reaction, however to get rid of isolation problem, we were thinking of employing greener solvent which will give good conversion as well as avoid extra purification steps to get the desired product in pure form. When we talk about the green solvent, water stands as first choice not only because of it is cheap, ready availability and non-toxic nature¹³ but also due to its ability to enhance the rates and affect the selectivity in various organic transformations due to unique polarity and high hydrogen bonding ability.¹⁴ Hence we also attempted the model reaction in water without any additional catalyst and the obtained results were very delightful. When we performed the reaction of isatin 1a (1 mmol) with 3-methyl-2-pyrazolin-5-one 2a (1 mmol) in 5 ml tap water, at the beginning of the reaction, we observe the reaction mixture as a reddish color. As reaction proceeded towards the desired product formation, the color of the reaction mixture was changed from reddish to orange to pale yellow. Finally after 10 min, we found the formation of a thick white color precipitate (Fig. 2). The obtained white color precipitate was filtered, dried and subjected to spectroscopic analysis. We were pleased to recognize the white color solid obtained in the reaction performed in water as a desired product with 100% conversion (entry 7, Table 1).

Table 1 Optimization of reaction condition^a

Entry	Solvent	Time	Conversion^b	Isolated yield 3a
a Reaction conditions: isatin 1a (1 mmol), 3-methyl-2-pyrazolin-5-one 2a (1 mmol) in 5 ml of solvent at rt.b By 1H NMR analysis.c The pure water was obtained by distillation of tap water and further purified by reverse osmosis.d HPLC grade water was obtained from Sigma-Aldrich.e In 3 ml water.f In 2 ml water.g Under solvent-free reaction condition.
1	DMF	1 h	82	71
2	DMSO	1 h	86	73
3	CH3CN	1 h	51	44
4	THF	1 h	31	27
5	MeOH	1 h	54	43
6	EtOH	1 h	50	42
7	Tap H2O	10 min	100	99
8	Distilled H2O^c	10 min	100	99
9	HPLC H2O^d	10 min	100	98
10	Tap H2O^e	10 min	100	98
11	Tap H2O^f	10 min	100	98
12	—^g	24 h	—	—
13	[bmim]BF4	24 h	—	—

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Fig. 2 (A) Unstirred reaction mixture of isatin 1a (1 mmol), 3-methyl-2-pyrazolin-5-one 2a (1 mmol) in 5 ml tap water at rt. (B) Immediate after stirring starts. (C) During stirring after 5 min. (D) During stirring after 10 min (at end of the reaction).

The problem of product isolation associated with solvents like DMSO, DMF was rectified when we employed water in the reaction. It is interesting to note that the progress of the reaction can be monitored just by visualization of the change of color of reaction mixture from red (at the beginning of the reaction) to white (at the end of the reaction). Furthermore the desired product was obtained in highly pure form just by filtration and does not require any column chromatographic purification. As a part of the study we have also performed the reaction in distilled as well as HPLC grade water and similar results were obtained as obtained with tap water (entry 8, 9 Table 1).

Reaction can even perform in less quantity of water to get the desired product however the dilution of reaction mixture requires for the filtration process as it forms a thick precipitate (entry 10, 11). With these observations, we have selected the stirring of isatin 1a (1 mmol) with 3-methyl-2-pyrazolin-5-one 2a (1 mmol) in 5 ml tap water for 10 min at rt as optimized reaction condition to afford quantitative yield of desired product 3a under catalyst-free and column chromatography-free reaction condition (entry 7, Table 1).

With this established optimum condition, we were intended to explore the scope and limitations of the developed protocol with several structurally varied isatins as well as 2-pyrazolin-5-one derivatives and results are incorporated in Table 2. We were delighted to find that, array of isatin derivatives with diverse functional groups were well-tolerated and afforded desired products in quantitative yield with very good purity under optimized condition (Table 2). To be specific, a 3-methyl-2-pyrazolin-5-one 2a reacted smoothly with halogenated isatins like 5-fluoro isatin, 5-chloro isatin, 5-iodo isatin to give the desired products in very good isolated yields (Table 2, entries 2–4).

Table 2 Synthesis of 3-pyrazolone substituted 3-hydroxy-2-oxindole frameworks under aqueous reaction medium^a

a Reaction conditions: isatin 1(a–l) (1 mmol), 2-pyrazolin-5-one derivative 2(a–c) (1 mmol) in 5 ml of tap water at rt and yields are given as an isolated yields. All products 3(a–p) were characterized by NMR, Mass and IR spectroscopic techniques (see ESI file for characterization data and copies of ¹H and ¹³C NMR spectrum).

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Similarly the reaction of 3-methyl-2-pyrazolin-5-one 2a with other isatin electrophiles like 5-nitro isatin, 5-methoxy isatin and 5-(trifluoromethoxy) isatin afforded desired products 3e, 3f, 3g within very short period of time (Table 2, entry 5, 6, 7 respectively). The reaction was not only successful with isatins having electron withdrawing substituent but also with isatin bearing electron donating group like 5-methyl isatin (Table 2, entry 8). As like mono-substituted isatins, di-substituted isatin like 4,7-dichloro isatin and 5,7-dimethyl isatin reacted in the same way and yielded the desired products under standard reaction condition (Table 2, entry 9 and 16 respectively). The scope of this catalyst-free and column chromatography-free protocol was further extended to N-alkylated isatins like N-methy isatin and N-phenyl isatin which also afforded their respective products 3j, 3k in high yield and purity (Table 2, entry 10, 11). For the general validity of the developed method, we were keen to explore the reactivity of other 2-pyrazolin-5-one nucleophiles with isatin electrophiles. In this context we screened 3-(trifluoromethyl)-2-pyrazolin-5-one 2b and 3-propyl-2-pyrazolin-5-one 2c with different isatins under optimized reaction condition. We observed that the reaction worked well with these substrates also and afforded respective products in very good yield (Table 2, entries 12–16).

One of the most unique features of this protocol is that, it works just “on water” under catalyst-free or additive-free reaction conditions. Moreover, this transformation is clean and easy to work up which affords desired products in very high yield and purity. Further, in order to demonstrate the scale-up potential of this efficient protocol, we conducted a gram-scale synthesis of 3a and 3m (Scheme 2). We performed the reaction of isatin 1a (0.3 mol, 44.14 g) with 3-methyl-2-pyrazolin-5-one 2a (0.3 mol, 35.14 g) in 1500 ml tap water at rt (entry1, Scheme 2). Similarly we performed the reaction of isatin 1a (0.3 mol, 44.14 g) with 3-propyl-2-pyrazolin-5-one 2b (0.3 mol, 39.94 g) in 1500 ml tap water at rt (entry 2, Scheme 2). The desired products 3a and 3m were obtained in pure form with very good isolated yield (98%, 97% respectively) under this catalyst-free and column chromatography-free protocol.

Scheme 2 Gram-scale synthesis of compound 3a and 3m.

As a part of the study, to know the effect of substituent's size and position present in 2-pyrazolin-5-one derivative on the success of the reaction, further study was planned. In this regards, we performed the reactions of 3-tert-butyl-1-methyl-2-pyrazolin-5-one 2d with different isatins under optimized reaction condition (Scheme 3). It was observed that the reaction of 3-tert-butyl-1-methyl-2-pyrazolin-5-one 2d with isatins does not proceed towards product formation even after stretching the reaction time up to 24 h. This observation indicates the adverse effect of bulkiness of substituent present in 3-tert-butyl-1-methyl-2-pyrazolin-5-one on the success of reaction. Similarly when we screened 3,4-dimethyl-2-pyrazolin-5-one 2e with different isatins, we does not observed any product formation up to longer reaction time. Furthermore we have also performed the reaction of 2d and 2e with isatin under reflux (100 °C, 24 h) as well as microwave heating condition (101 °C, 140 W, 15 min) but the formation of new product was not observed. Although these observations were surprising, these led us to establish the proper mechanistic sequence of the reaction.

Scheme 3 Effect of substituent's size and position present in 2-pyrazolin-5-one derivative on the success of reaction.

The formation of the desired product can be visualized by two possible pathways (Scheme 4). As depicted in path 1, reaction can proceeds by, formation of enolate of 3-methyl-2-pyrazolin-5-one, aldol reaction type addition of enolate of 3-methyl-2-pyrazolin-5-one on isatin 1a to give aldol addition product B, followed by tautomerization of aldol addition product B to give desired product 3a. Likewise, as depicted in path 2, reaction can proceeds by, formation of tautomer of 3-methyl-2-pyrazolin-5-one, nucleophilic addition type reaction of tautomer of 3-methyl-2-pyrazolin-5-one on isatin 1a to form product C, followed by aromatization of product C to give desired product 3a. We believe that the reaction does not proceeds via enolate formation, because we did not observe the formation of aldol addition product A when we treated 3,4-dimethyl-2-pyrazolin-5-one 2e with isatin 1a under optimized reaction condition. With this observation, we proposed the formation of desired products 3a via a mechanistic sequence shown in path 2 in Scheme 4.

Scheme 4 Reasoned mechanistic sequences for the formation of the desired product 3a in this reaction.

Conclusions

In summary, we have developed an “on water” efficient protocol for the synthesis of a novel class of functionalized 3-(2-pyrazolin-5-one derivatives) substituted, 3-hydroxy-2-oxindoles frameworks under catalyst-free and column chromatography-free conditions at rt. The development of this method led to a rapid and general route for the straightforward preparation of medicinally important 3-hydroxy-2-oxindole structural scaffolds in quantitative yields under very mild reaction condition from readily available starting materials. In addition to simplicity, this method has one salient feature in its ability to tolerate a variety of functionalized isatins as well as 2-pyrazolin-5-one derivatives. Such a 3-hydroxy-2-oxindole framework with diverse functionality provides an additional functional handle for further transformations which can be effectively utilized in preparation of a library of pharmaceutically important compounds.

Experimental

General procedure for the rapid and atom economical synthesis of 3-(2-pyrazolin-5-one derivatives) substituted, 3-hydroxy-2-oxindole frameworks under catalyst-free and column chromatography free condition using tap water

Mixture of isatin 1(a–l) (1.0 mmol) and 2-pyrazolin-5-one derivatives 2(a–c) (1 mmol) was stirred in 5 ml tap water at room temperature for stipulated time (10 min). The progress of the reaction was monitored by visualisation of the change of color of reaction mixture from red (at the start of the reaction) to white (at the end of the reaction). The progress of the reaction was also confirmed by TLC. The obtained thick white precipitate was filtered and dried to afford the desired product 3(a–p) in very good yield and purity. All products 3(a–p) were characterized by NMR, Mass and IR spectroscopic techniques (see ESI† file for characterization data and copies of ¹H and ¹³C NMR spectrum). (Note that the signal for –OH and –NH proton of pyrazol ring of the products remains undetectable in ¹H NMR spectrum which might be due to the rapid exchange ability of such protons.)

Spectral data for all the synthesized compounds 3(a–p)

3-Hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)indolin-2-one (3a, Table 2). Yield, 99%; time 10 min; pale yellow solid; mp 226–228 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.19 (s, 1H), 7.24–7.03 (m, 2H), 6.90 (t, J = 7.3 Hz, 1H), 6.78 (d, J = 7.7 Hz, 1H), 6.29 (br s, 1H), 2.07 (s, 3H), ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 178.16, 158.66, 141.65, 137.41, 133.08, 128.75, 124.57, 121.40, 109.37, 100.41, 73.84, 11.23 ppm; IR (KBr): ν = 3377, 3184, 3152, 1692, 1612, 1470, 1386, 1193, 788, 753, 664, 596 cm⁻¹; MS (ESI): m/z = 268 [M + Na]⁺; HRMS (ESI): m/z calcd for C₁₂H₁₁O₃N₃Na [M + Na]⁺ = 268.06926, found 268.06873.

5-Fluoro-3-hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)indolin-2-one (3b, Table 2). Yield, 99%; time 10 min; white solid, mp 194–196 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.21 (s, 1H), 7.06–6.87 (m, 2H), 7.78–6.74 (m, 1H), 6.32 (br s, 1H), 2.18 (s, 3H), ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ: 178.40, 159.13, 158.67, 157.24, 138.45, 137.96, 135.21, 135.14, 115.21, 115.03, 112.28, 112.18, 110.20, 110.14, 100.33, 74.23, 11.70 ppm; IR (KBr): ν = 3370, 3145, 2765, 1694, 1625, 1487, 1381, 1322, 1270, 1194, 1150, 1048, 821, 658, 610 cm⁻¹; MS (ESI): m/z = 264 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₂H₁₁O₃N₃F [M + H]⁺ = 264.07790, found 264.07764.

5-Chloro-3-hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)indolin-2-one (3c, Table 2). Yield, 99%; time 10 min; white solid; mp 196–198 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.22 (s, 1H), 7.23–6.98 (m, 2H), 6.75 (d, J = 7.9 Hz, 1H), 6.50 (br, 1H), 2.00 (s, 3H), ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 177.96, 158.67, 140.49, 138.10, 135.13, 128.44, 125.71, 124.54, 110.87, 99.90, 79.92, 11.43 ppm; IR (KBr): ν = 3479, 3087, 2822, 2725, 1696, 1586, 1445, 1321, 1183, 819, 781 cm⁻¹; MS (ESI): m/z = 302 [M + Na]⁺; HRMS (ESI): m/z calcd for C₁₂H₁₀O₃N₃ClNa [M + Na]⁺ = 302.03029, found 302.02921.

3-Hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)-5-iodoindolin-2-one (3d, Table 2). Yield, 99%; time 10 min; white solid; mp 218–220 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.27 (s, 1H), 7.55–7.38 (m, 2H), 6.66 (d, J = 8.4 Hz, 1H), 6.59 (br s, 1H), 2.00 (s, 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 177.37, 158.62, 141.32, 137.63, 136.96, 135.61132.61, 111.79, 99.68, 83.60, 73.62, 11.15 ppm; IR (KBr): ν = 3023, 2957, 2771, 1718, 1617, 1467, 1435, 1233, 1178 cm⁻¹; MS (ESI): m/z = 372 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₂H₁₁O₃N₃I [M + H]⁺ = 371.98396, found 371.98291.

3-Hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)-5-nitroindolin-2-one (3e, Table 2). Yield, 99%, time 10 h; white solid; mp 193–195 °C. ¹H NMR (300 MHz, DMSO-d₆) δ 10.84 (s, 1H), 8.13 (dd, J = 8.4, 1.1 Hz, 1H), 8.03 (d, J = 1.1 Hz, 1H), 6.98 (dd, J = 8.4, Hz, 1H), 6.62 (br s, 1H), 2.20 (s 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 178.75, 159.19, 148.12, 142.53, 139.22, 133.86, 125.99, 120.24, 109.85, 99.33, 73.68, 11.50 ppm; IR (KBr): ν = 3528, 3050, 1714, 1586, 1527, 1415, 1345, 1302, 1256, 1183, 1107, 903, 836, 783, 740, 603 cm⁻¹; MS (ESI): m/z = 291 [M + H]⁺. HRMS (ESI): m/z calcd for C₁₂H₁₁O₅N₄ [M + H]⁺ = 291.07240, found 291.07138.

3-Hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)-5-methoxyindolin-2-one (3f, Table 2). Yield, 99%; time 10 min; white solid; mp 193–195 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.04 (s, 1H), 6.86–6.68 (m, 3H), 6.28 (br s, 1H), 3.66 (s, 3H), 2.06 (s, 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 178.31, 158.89, 154.96, 137.84, 135.03, 134.48, 113.64, 111.54, 109.99, 100.62, 74.40, 55.52, 11.49 ppm; IR (KBr): ν = 3415, 3361, 3201, 2929, 2835, 2563, 1711, 1607, 1533, 1494, 1365, 1290, 1210, 1159, 1029, 815, 640 cm⁻¹; MS (ESI): m/z = 298 [M + Na]⁺; HRMS (ESI): m/z calcd for C₁₃H₁₃O₄N₃Na [M + Na]⁺ = 298.07983, found 298.07907.

3-Hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)-5-(trifluoromethoxy)indolin-2-one (3g, Table 2). Yield, 99%; time 10 min; white solid; mp 193–195 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.43 (s, 1H), 7.22–6.99 (m, 2H), 6.83 (d, J = 9.1 Hz, 1H), 6.42 (br s, 1H), 2.1 (s, 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 178.34, 158.89, 143.33, 140.79, 138.21, 134.77, 130.97, 121.87, 118.12, 110.32, 99.79, 74.02, 11.39 ppm; IR (KBr): ν = 3372, 3201, 2569, 1727, 1600, 1533, 1487, 1275, 1186 cm⁻¹; MS (ESI): m/z = 330 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₃H₁₁O₄N₃F₃ [M + H]⁺ = 330.06962, found 330.06888.

Ethyl 3-hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)-5-methylindolin-2-one (3h, Table 2). Yield, 94%; time 10 min; grey-white solid; mp 197–198 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.10 (s, 1H), 7.08–6.83 (m, 2H), 6.67 (d, J = 8.7 Hz, 1H), 6.22 (br s, 1H), 2.21 (s, 3H), 2.09 (s, 3H) ppm; 178.46, 158.86, 141.85, 137.61, 133.28, 128.95, 124.77, 121.60, 110.07, 99.87, 73.64, 22.56, 11.22 ppm; IR (KBr): ν = 3414, 3345, 3197, 2923, 2563, 1713, 1629, 1532, 1492, 1366, 1149, 816 cm⁻¹; MS (ESI): m/z = 260 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₃H₁₄O₃N₃[M + H]⁺ = 260.10352, found 260.10278.

4,7-Dichloro-3-hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)indolin-2-one (3i, Table 2). Yield, 98%; time 10 min; white solid; mp 138–140 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.61 (br s, 1H), 7.76 (s, 1H), 7.08 (d, J = 8.4 Hz, 1H), 6.78 (d, J = 8.4 Hz, 1H), 2.07 (s, 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 177.39, 161.16, 141.32, 139.55, 130.29, 129.77, 129.09, 123.11, 112.56, 97.39, 75.19, 11.53 ppm; IR (KBr): ν = 3156, 1731, 1613, 1466, 1163, 795 cm⁻¹; MS (ESI): m/z = 314 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₂H₁₀O₃N₃Cl₂ [M + H]⁺ = 314.00937, found 314.00882.

3-Hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)-1-methylindolin-2-one (3j, Table 2). Yield, 99%; time 10 min; white solid; mp 141–143 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 7.37–7.18 (m, 2H), 7.00 (t, J = 7.7, Hz, 1H), 6.90 (d, J = 7.7 Hz, 1H), 6.59 (br s, 1H), 3.15 (s, 3H), 1.99 (s, 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 176.81, 159.13, 143.20, 138.25, 132.42, 129.31, 124.36, 122.57, 108.47, 100.48, 73.94, 26.12, 11.41 ppm; IR (KBr): ν = 3256, 2523, 1706, 1612, 1515, 1470, 1377, 1089, 1040, 921, 785, 749, 688 cm⁻¹; MS (ESI): m/z = 260 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₃H₁₄O₃N₃[M + H]⁺ = 260.10352, found 260.10278.

3-Hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)-1-phenylindolin-2-one (3k, Table 2). Yield, 99%; time 10 min; white solid; mp 174–176 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 7.98–6.95 (m, 9H), 6.67 (br s, 1H), 2.06 (s, 3H) ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ: 175.88, 158.42, 142.68, 137.67, 134.44, 132.32, 129.19, 128.57, 127.52, 126.30, 124.47, 122.59, 108.53, 100.68, 73.72, 11.27 ppm; IR (KBr): ν = 3472, 3299, 3062, 2561, 1712, 1614, 1529, 1465, 1376, 1188, 760, 698 cm⁻¹; MS (ESI): m/z = 322 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₈H₁₆O₃N₃ [M + H]⁺ = 322.11862, found 322.11807.

3-(5-(Trifluoromethyl)-3-hydroxy-1H-pyrazol-4-yl)-3-hydroxyindolin-2-one (3l, Table 2). Yield, 92%; time 10 min; pale yellow solid; mp 181–183 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 11.16 (br s, 1H), 10.73 (br s, 1H), 7.8 (d, J = 7.4 Hz, 1H), 7.36 (t, J = 7.4 Hz, 1H), 7.04 (t, J = 7.4 Hz, 1H), 6.92 (d, J = 7.4 Hz, 1H), ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 164.39, 163.46, 160.52, 142.39, 137.62, 131.14, 123.63, 122.68, 120.81, 120.41, 119.36, 113.50, 109.54, 90.20, 75.10 ppm; IR (KBr): ν = 3404, 3304, 3198, 1709, 1684, 1615, 1513, 1461, 1351, 1180, 1124, 786 cm⁻¹; MS (ESI): m/z = 300 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₂H₉O₃N₃F₃ [M + H]⁺ = 300.05905, found 300.05842.

3-Hydroxy-3-(3-hydroxy-5-propyl-1H-pyrazol-4-yl)indolin-2-one (3m, Table 2). Yield: 99%; time 10 min; white solid; mp 184–186 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.21 (s, 1H), 7.23–7.06 (m, 2H), 6.90 (d, J = 7.2 Hz, 1H), 6.78 (d, J = 7.5 Hz, 1H), 6.32 (br s, 1H), 2.47–2.28 (m, 2H), 1.59–1.38 (m, 2H), 0.78 (t, J = 7.2 Hz, 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 178.18, 158.63, 141.79, 141.62, 133.09, 128.84, 124.51, 121.41, 109.34, 99.67, 74.04, 27.25, 22.44, 13.77 ppm; IR (KBr): ν = 3371, 3215, 2962, 2560, 1737, 1698, 1625, 1598, 1530, 1471, 1378, 1183, 1182, 1105, 754 cm⁻¹; MS (ESI): m/z = 274 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₄H₁₆O₃N₃ [M + Na]⁺ = 274.11862, found 274.11867.

5-Fluoro-3-hydroxy-3-(3-hydroxy-5-propyl-1H-pyrazol-4-yl)indolin-2-one (3n, Table 2). Yield, 99%; time 10 min; white solid; mp 170–172 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.23 (s, 1H), 7.04–6.97 (m, 1H), 6.92–6.89 (m, 1H), 6.79–6.75 (m, 1H), 6.36 (br s, 1H), 2.63–2.52 (m, 1H), 2.48–2.20 (m, 1H), 1.60–1.47 (m, 2H), 0.82 (t, J = 7.2 Hz, 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 178.12, 159.46, 158.35, 156.32, 142.05, 137.93, 135.05, 134.96, 115.07, 114.76, 112.08, 111.76, 110.13, 110.03, 99.34, 74.24, 27.36, 22.54, 13.79 ppm; IR (KBr): ν = 3371, 3214, 2963, 2875, 2558, 1739, 1696, 1596, 1529, 1489, 1311, 1187, 1147, 815, 701, 596 cm⁻¹; MS (ESI): m/z = 292 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₄H₁₅O₃N₃F [M + H]⁺ = 292.10920, found 292.10912.

5-Chloro-3-hydroxy-3-(3-hydroxy-5-propyl-1H-pyrazol-4-yl)indolin-2-one (3o, Table 2). Yield, 98%; time 10 min; white solid; mp 182–184 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.33 (s, 1H), 7.21 (dd, J = 8.3, 2.1 Hz, 1H), 7.04 (d, J = 2.1 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 6.34 (br s, 1H), 2.73–2.52 (m, 2H), 1.65–1.46 (m, 2H), 0.84 (t, J = 7.3 Hz, 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 177.79, 158.21, 142.15, 140.70, 135.45, 128.46, 125.23, 124.34, 110.80, 99.33, 74.00, 27.42, 22.63, 13.79 ppm; IR (KBr): ν = 3376, 3203, 2963, 2873, 2558, 1740, 1692, 1596,1529, 1480, 1178, 822 cm⁻¹; MS (ESI): m/z = 308 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₄H₁₅O₃N₃Cl [M + H]⁺ = 308.07965, found 308.07976.

3-Hydroxy-3-(3-hydroxy-5-propyl-1H-pyrazol-4-yl)-5,7-dimethylindolin-2-one (3p, Table 2). Yield, 91%; time 10 min; grey-white solid; mp 160–162 °C; ¹H NMR (300 MHz, DMSO-d₆) δ: 10.18 (s, 1H), 6.82 (s, 1H), 6.76 (s, 1H), 6.29 (br s, 1H), 2.43–2.22 (m, 2H), 2.17 (s, 3H), 2.15 (s, 3H), 1.67–1.32 (m, 2H), 0.77 (t, J = 7.2 Hz, 3H) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ: 178.63, 158.78, 141.42, 137.79, 132.73, 130.44, 130.09, 122.51, 118.22, 99.82, 74.40, 27.18, 22.44, 20.49, 16.16, 13.75 ppm; IR (KBr): ν = 3212, 2977, 2806, 1713, 1596, 1469, 1428, 1315, 1210, 1144, 741 cm⁻¹; MS (ESI): m/z = 302 [M + H]⁺; HRMS (ESI): m/z calcd for C₁₆H₂₀O₃N₃ [M + H]⁺ = 302.14992, found 302.15002.

Acknowledgements

PBT thanks CSIR New Delhi for the award of senior research fellowship and Dr Ahmed Kamal (Outstanding Scientist), Head, Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad for his support and encouragement.

Notes and references

1. (a) P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice, Oxford University Press, Oxford, 1998; (b) A. S. Matlack, Introduction to Green Chemistry, ed. D. Marcel, New York, 2001; (c) M. Lancaster, Green Chemistry: An Introductory Text, RSC Editions, London, 2002.
2. (a) A. Kumar and S. Sharma, Green Chem., 2011, 13, 2017–2020; (b) A. Kumar, G. Gupta and S. Srivastava, Green Chem., 2011, 13, 2459–2463; (c) A. Kumar, M. K. Gupta and M. Kumar, Green Chem., 2012, 14, 290–295; (d) K. Tanaka, T. Sugino and F. Toda, Green Chem., 2000, 2, 303–304; (e) C. L. Raston and J. L. Scott, Green Chem., 2000, 2, 49–52; (f) P. T. Anastas and T. Williamson, Green Chemistry: Frontiers in Benign Chemical Synthesis and Process, Oxford University Press, Oxford, UK, 1998; (g) J. McNulty and P. Das, Eur. J. Org. Chem., 2009, 24, 4031–4035; (h) J. McNulty and P. Das, Tetrahedron Lett., 2009, 50, 5737–5740; (i) J. McNulty, P. Das and D. McLeod, Chem.–Eur. J., 2010, 16, 6756–6760; (j) P. Das and J. McNulty, Tetrahedron Lett., 2010, 51, 3197–3199; (k) P. Das, D. McLeod and J. McNulty, Tetrahedron Lett., 2011, 52, 199–201.
3. (a) A. Domling, Chem. Rev., 2006, 106, 17–89; (b) Multi-component Reaction, ed. J. Zhu and H. Bienayme, Wiley-VCH, Weinheim, 2005; (c) D. J. Raman and M. Yus, Angew. Chem., Int. Ed., 2005, 44, 1602–1634.
4. For recent reviews, see: (a) T. Tokunaga, W. E. Hume, T. Umezome, K. Okazaki, Y. Ueki, K. Kumagai, S. Hourai, J. Nagamine, H. Seki, M. Noguchi and R. Nagata, J. Med. Chem., 2001, 44, 4641–4649; (b) A. B. Dounay and L. E. Overman, Chem. Rev., 2003, 103, 2945–2964; (c) J. P. Michael, Nat. Prod. Rep., 2005, 22, 627–646; (d) T. Kagata, S. Saito, H. Shigemori, A. Ohsaki, H. Kubota and J. Kobayashi, J. Nat. Prod., 2006, 69, 1517–1521; (e) S. Peddibhotla, Curr. Bioact. Compd., 2009, 5, 20–38; (f) J. J. Badillo, N. V. Hanhan and A. K. Franz, Curr. Opin. Drug Discovery Dev., 2010, 13, 758–776; (g) C. Marti and E. M. Carreira, Eur. J. Org. Chem., 2003, 2209–2219; (h) C. V. Galliford and K. A. Scheidt, Angew. Chem., Int. Ed., 2007, 46, 8748–8758; (i) H. Lin and S. J. Danishefsky, Angew. Chem., Int. Ed., 2003, 42, 36–51; (j) F. Zhou, Y.-L. Liu and J. Zhou, Adv. Synth. Catal., 2010, 352, 1381–1407.
5. (a) P. Hewawasam, N. A. Meanwell, V. K. Gribkoff, S. I. Dworetzky and C. G. Boissard, Bioorg. Med. Chem. Lett., 1997, 7, 1255–1260; (b) N. Boechat, W. B. Kover, V. Bongertz, M. M. Bastos, N. C. Romeiro, M. L. G. Azavedo and W. Wollinger, Med. Chem., 2007, 3, 533–542; (c) P. Hewawasam, M. Erway, S. L. Moon, J. Knipe, H. Weiner, C. G. Boissard, D. J. Post-Munson, Q. Gao, S. Huang, V. K. Gribkoff and N. A. Meanwell, J. Med. Chem., 2002, 45, 1487–1499.
6. For selected examples, see: (a) S. Lee and J. F. Hartwig, J. Org. Chem., 2001, 66, 3402–3415; (b) A. B. Dounay, K. Hatanaka, J. J. Kodanko, M. Oestreich, L. E. Overman, L. A. Pfeifer and M. M. Weiss, J. Am. Chem. Soc., 2003, 125, 6261–6271; (c) I. D. Hills and G. C. Fu, Angew. Chem., Int. Ed., 2003, 42, 3921–3924; (d) B. M. Trost and M. U. Frederiksen, Angew. Chem., Int. Ed., 2005, 44, 308–310; (e) Y. X. Jia, J. M. Hillgren, E. L. Watson, S. P. Marsden and E. P. Kündig, Chem. Commun., 2008, 4040–4042; (f) Y. X. Jia and E. P. Kündig, Angew. Chem., Int. Ed., 2009, 48, 1636–1639.
7. (a) M. Himly, B. Jahn-Schmid, K. Pittertschatscher, B. Bohle, K. Grubmayr, F. Ferreira, H. Ebner and C. Ebner, J. Allergy Clin. Immunol., 2003, 111, 882–888; (b) T. Watanabe, S. Yuki, M. Egawa and H. Nishi, J. Pharmacol. Exp. Ther., 1994, 268, 1597–1604; (c) H. Kawai, H. Nakai, M. Suga, S. Yuki, T. Watanabe and K. I. Saito, J. Pharmacol. Exp. Ther., 1997, 281, 921–927; (d) T. W. Wu, L. H. Zeng, J. Wu and K. P. Fung, Life Sci., 2002, 71, 2249–2255; (e) M. A. Al-Haiza, S. A. El-Assiery and G. H. Sayed, Acta Pharm. (Zagreb, Croatia), 2001, 51, 251–261; (f) D. Castagnolo, F. Manetti, M. Radi, B. Bechi, M. Pagano, A. De Logu, R. Meleddu, M. Saddi and M. Botta, Bioorg. Med. Chem., 2009, 17, 5716–5721; (g) F. Moreau, N. Desroy, J. M. Genevard, V. Vongsouthi, V. Gerusz, G. Le Fralliec, C. Oliveira, S. Floquet, A. Denis, S. Escaich, K. Wolf, M. Busemann and A. Aschenbsenner, Bioorg. Med. Chem. Lett., 2008, 18, 4022–4026; (h) E. A. M. Badawey and I. M. El-Ashmawey, Eur. J. Med. Chem., 1998, 33, 349–361; (i) F. A. Pasha, M. Muddassar, M. M. Neaz and S. J. Cho, J. Mol. Graphics Modell., 2009, 28, 54–61; (j) C. E. Rosiere and M. I. Grossman, Science, 1951, 113, 651–653; (k) D. M. Bailey, P. E. Hansen, A. G. Hlavac, E. R. Baizman, J. Pearl, A. F. Defelice and M. E. Feigenson, J. Med. Chem., 1985, 28, 256–260; (l) P. M. S. Chauhan, S. Singh and R. K. Chatterjee, Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 1993, 32, 858–861; (m) P. Gunasekaran, S. Perumal, P. Yogeeswari and D. Sriram, Eur. J. Med. Chem., 2011, 46, 4530–4536; (n) H. Shiohara, H. Fujikura, N. Fushimi, F. Ito and M. Isaji, PCT Int. Appl. WO 2002098893, 2002; Chem. Abstr., 2003, 138, 2491724925; (o) N. Foloppe, L. M. Fisher, R. Howes, A. Potter, A. G. S. Robertson and A. E. Surgenor, Bioorg. Med. Chem., 2006, 14, 4792–4802; (p) D. A. Barawkar, A. Meru, A. Bandyopadhyay, A. Banerjee, A. M. Deshpande, C. Athare, C. Kodurum, G. Khose, J. Gundu, K. Mahajan, P. Patil, S. R. Kandalkar, S. Niranjan, S. Bhosale, S. De, S. Mukhopadhyay, S. Chaudhary, S. Koul, U. Singh, A. Chugh, V. P. Palle, K. A. Mookhtiar, J. Vacca, P. K. Chakravarty, R. P. Nargund, S. D. Wright, S. Roy, M. P. Graziano, S. B. Singh, D. Cully and T. Q. Cai, ACS Med. Chem. Lett., 2011, 2, 919–923; (q) D. A. Barawkar, A. Bandyopadhyay, A. Deshpande, S. Koul, S. Kandalkar, P. Patil, G. Khose, S. Vyas, M. Mone, S. Bhosale, U. Singh, S. De, A. Meru, J. Gundu, A. Chugh, V. P. Palle, K. A. Mookhtiar, J. P. Vacca, P. K. Chakravarty, R. P. Nargund, S. D. Wright, S. Roy, M. P. Graziano, D. Cully, T. Q. Cai and S. B. Singh, Bioorg. Med. Chem. Lett., 2012, 22, 4341–4347.
8. For reviews on pyrazolines, see: (a) A. Levai, J. Heterocycl. Chem., 2002, 39, 1–13; (b) M. Kissane and A. R. Maguire, Chem. Soc. Rev., 2010, 39, 845–883; (c) C. H. Kuchenthal and W. Maison, Synthesis, 2010, 5, 719–740.
9. For selected examples, see: (a) R. K. Boeckman Jr, J. E. Reed and P. Ge, Org. Lett., 2001, 3, 3651–3653; (b) M. Abass and B. B. Mostafa, Bioorg. Med. Chem., 2005, 13, 6133–6144; (c) M. S. Chande, P. A. Barve and V. Suryanarayan, J. Heterocycl. Chem., 2007, 44, 49–53; (d) G. Mariappan, B. P. Saha, N. R. Bhuyan, P. R. Bharti and D. Kumar, J. Adv. Pharm. Technol. Res., 2010, 1, 260–267; (e) R. Ma, J. Zhu, J. Liu, L. Chen, X. Shen, H. Jiang and J. Li, Molecules, 2010, 15, 3593–3601; (f) Y. H. Liao, W. B. Chen, Z. J. Wu, X. L. Du, L. F. Cun, X. M. Zhang and W. C. Yuan, Adv. Synth. Catal., 2010, 352, 827–832; (g) S. Gogoi and C. G. Zhao, Tetrahedron Lett., 2009, 50, 2252–2255; (h) M. Radi, V. Bernardo, B. Bechi, D. Castagnolo, M. Pagano and M. Botta, Tetrahedron Lett., 2009, 50, 6572–6575; (i) S. Gogoi, C. G. Zhao and D. Ding, Org. Lett., 2009, 11, 2249–2252; (j) Z. G. Yang, Z. Wang, S. Bai, X. Liu, L. Lin and X. Feng, Org. Lett., 2011, 13, 596–599; (k) A. N. Alba, A. Zea, G. Valero, T. Calbet, M. Font-Bardia, A. Mazzanti, A. Moyano and R. Rios, Eur. J. Org. Chem., 2011, 1318–1325; (l) Z. Wang, Z. Yang, D. Chen, X. Liu, L. Lin and X. Feng, Angew. Chem., Int. Ed., 2011, 50, 4928–4932; (m) M. R. Rohman, H. Mecadon, A. T. Khan and B. Myrboh, Tetrahedron Lett., 2012, 53, 5261–5264; (n) J. W. Wu, F. Li, Y. Zheng and J. Nie, Tetrahedron Lett., 2012, 53, 4828–4831; (o) P. P. Ghosh, G. Pal, S. Paul and A. R. Das, Green Chem., 2012, 14, 2691–2698; (p) Y. Liu, Z. Ren, W. Cao, J. Chen, H. Deng and M. Shao, Synth. Commun., 2011, 41, 3620–3626; (q) M. N. Elinson, A. I. Ilovaisky, V. M. Merkulova, G. I. Nikishin and T. A. Zaimovskaya, Mendeleev Commun., 2012, 22, 143–144; (r) R. G. Redkin, L. A. Shemchuk, V. P. Chernykh, O. V. Shishkin and S. V. Shishkina, Tetrahedron, 2007, 63, 11444–11450; (s) F. F. Abdel, R. A. Mekheimer, M. M. Mashaly and E. K. Ahmed, Collect. Czech. Chem. Commun., 1994, 59, 1235–1240; (t) K. C. Joshi, R. T. Pardasani, A. Dandia and S. Bhagat, Heterocycles, 1991, 32, 1491–1498; (u) N. Hussain, R. Dangi, C. K. Sharma and G. L. Talesara, Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 2011, 50, 885–889; (v) S. A. Metwally, M. I. Younes and H. H. Abbas, Acta Chim. Hung., 1989, 126, 591–597.
10. (a) H. M. Meshram, P. Ramesh, B. C. Reddy, B. Shreedhar and J. S. Yadav, Tetrahedron, 2011, 67, 3150–3155; (b) H. M. Meshram, D. A. Kumar, B. C. Reddy and P. Ramesh, Synth. Commun., 2010, 40, 39–45; (c) H. M. Meshram, P. Ramesh, A. S. Kumar and A. Swetha, Tetrahedron Lett., 2011, 52, 5862–5864; (d) H. M. Meshram, R. N. Nageswara, R. L. Chandrasekhara and S. N. Kumar, Tetrahedron Lett., 2012, 53, 3963–3966; (e) P. B. Thakur, K. Sirisha, A. V. S. Sarma, J. B. Nanubolu and H. M. Meshram, Tetrahedron, 2013, 69, 6415–6423.
11. (a) F. D. Popp, Adv. Heterocycl. Chem., 1975, 18, 1–58; (b) J. F. M. da Silva, S. J. Garden and A. C. Pinto, J. Braz. Chem. Soc., 2001, 12, 273–324.
12. (a) G. Choudhary and R. K. Peddinti, Green Chem., 2011, 13, 276–282; (b) S. Kumar, P. Sharma, K. K. Kapoor and M. S. Hundal, Tetrahedron, 2008, 64, 536–542; (c) J. Zhang, Z. Cui, F. Wang, Y. Wang, Z. Miao and R. Chen, Green Chem., 2007, 9, 1341–1345; (d) A. Kumar, M. Kumar and M. K. Gupta, Green Chem., 2012, 14, 2677–2681; (e) G. R. Qu, H. L. Zhang, H. Y. Niu, Z. K. Xue, X. X. Lva and H. M. Guo, Green Chem., 2012, 14, 1877–1879; (f) F. E. A. Van Waes, J. Drabowicz, A. Cukalovica and C. V. Stevens, Green Chem., 2012, 14, 2776–2779; (g) F. Alonso, Y. Moglie, G. Radivoy and M. Yusa, Green Chem., 2012, 14, 2699–2702; (h) M. Jereb, Green Chem., 2012, 14, 3047–3052; (i) J. Liu, M. Lei and L. Hu, Green Chem., 2012, 14, 2534–2539; (j) B. D. Bala, S. M. Rajesh and S. Perumal, Green Chem., 2012, 14, 2484–2490; (k) R. Pelagalli, I. Chiarotto, M. Feroci and S. Vecchio, Green Chem., 2012, 14, 2251–2255; (l) C. Zhang, L. Zhanga and N. Jiao, Green Chem., 2012, 14, 3273–3276; (m) Z. N. Tisseh, M. Dabiri, M. Nobahar, H. R. Khavasi and A. Bazgir, Tetrahedron, 2012, 68, 1769–1773.
13. (a) H. C. Hailes, Org. Process Res. Dev., 2007, 11, 114–120; (b) C. J. Li and C. Liang, Chem. Soc. Rev., 2006, 35, 68–82.
14. (a) R. N. Butler and A. G. Coyne, Chem. Rev., 2010, 110, 6302–6337; (b) A. Chanda and V. V. Fokin, Chem. Rev., 2009, 109, 725–748; (c) V. Polshettiwar and R. S. Varma, Green Chem., 2010, 12, 743–754; (d) G. L. Khatik, R. Kumar and A. K. Chakraborti, Org. Lett., 2006, 8, 2433–2436; (e) N. Azizi and M. R. Saidi, Org. Lett., 2005, 7, 3649–3651; (f) N. Azizi, F. Aryanasab, L. Torkiyan, A. Ziyaei and M. R. J. Saidi, J. Org. Chem., 2006, 71, 3634–3635; (g) B. C. Ranu and S. Banerjee, Tetrahedron Lett., 2007, 48, 141–143; (h) S. Narayan, J. Muldoon, M. G. Finn, V. V. Fokin, H. C. Kolb and K. B. Sharpless, Angew. Chem., Int. Ed., 2005, 44, 3275–3279.

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Footnote

† Electronic supplementary information (ESI) available: Spectral data as well as copies of ¹H and ¹³C NMR spectrum. See DOI: 10.1039/c3ra46613b

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