Terminal alkyne homocoupling reactions catalyzed by an efficient and recyclable polymer-supported copper catalyst at room temperature under solvent-free conditions

Abstract

A highly efficient protocol for terminal alkyne homocoupling reaction to 1,4-disubstituted 1,3-diynes using a polymer-supported copper catalyst at room temperature under solvent conditions is presented. The reaction proceeds smoothly to provide the corresponding products in excellent to high yields within 10–20 min.

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1,3-Diyne derivatives are very important materials in the fields of biology and materials science, because they can be converted into various structural entities, especially in the construction of macrocyclic annulenes,¹ organic conductors,² supramolecular switches³ and carbon-rich materials.⁴ Therefore, much attention has been devoted to the development of new and efficient methods for the synthesis of diynes in recent years.⁵

Terminal alkynes homocoupling reaction, named after Glaser-type coupling, is a classic reaction to prepare 1,3-diynes.⁶ The catalyst system used commonly is the Pd,⁷ which involves Cu(I) salts as a co-catalyst because of their mild, efficient and selective properties. However, palladium reagents are expensive, and often required air-sensitive and poisonous phosphine ligands. In order to overcome these drawbacks, many modifications and improvements have been introduced into this area and single copper salts that catalyze the terminal alkynes homocoupling reactions have been reported quite recently. Jia and co-workers⁸ reported the homocoupling reactions of terminal alkynes using Cu(OAc)₂·H₂O as a catalyst in DMSO at 90 °C. Chen et al. reported a method for transforming terminal acetylenes into 1,3-diynes based on catalytic amounts of a Cu(II) salt under solvent free conditions.⁹ Room-temperature copper-mediated Glaser-type coupling reaction under the CuI–NBS–DIPEA promoting system has also been reported.¹⁰ However, most of these systems in this reaction still have the problems such as high temperature, solvent required, large amount of the catalyst and longer reaction time. Moreover, the catalysts could not be recycled and reused.

The utilization of renewable materials, room-temperature and solvent-free conditions are the key issues in a green synthetic strategy. Currently, great efforts in catalysis research have been devoted to the introduction and application of effective and safe heterogeneous catalysts.¹¹ The utilization of a polymer-supported catalyst offers several advantages in preparative procedures. Such catalysts are as active as their homogeneous counterparts while having the distinguishing characteristics of being easily separable from the reaction media, recyclability, enhanced stability, easier handling, non-toxicity and lower cost.¹²

Herein, in construction of our studies in polymer-supported catalyst and green chemistry,¹³ we present the polymer-supported catalyst and its evaluation in terminal alkyne homocoupling reaction. As expected, the catalyst could catalyze the coupling effectively at room temperature under solvent-free conditions within 10–20 min. Moreover, the catalyst could be easily recovered and reused several times without a significant loss in its activity.

The preparation of the polymer-supported catalyst was performed according to the literature (Scheme 1).¹⁴ In order to evaluate the activity of the polymer-supported copper catalyst for the terminal alkynes homocoupling reaction, the homocoupling reaction of 1-ethyl-4-ethynylbenzene was taken as a model reaction. In the preliminary experiment, the reaction was carried out in various solvents, with the supported complex (5 mol% of the copper content) as a catalyst and n-butylamine (0.5 eq.) as a base, in air at room temperature (Table 1). As can be seen in Table 1, AcOEt, toluene, CH₂Cl₂ and THF all gave the excellent yields of 89–92% (Table 1, entries 2–5). However, the polar solvents such as CH₃OH and DMSO were not reactive for this coupling reaction and poor yields were obtained (Table 1, entries 1 and 6). Then, we tried to investigate whether the reaction can be carried out under solvent-free conditions. As a result, the reaction surprisingly proceeded in high yields under solvent-free conditions and only 10 minutes were required (Table 1, entry 7). Considering the economic and environmentally friendly reaction, these solvent-free conditions are clearly the most favorable reaction system. Moreover, homogeneous Cu catalysts such as CuI, Cu(OAc)₂ and CuCl₂ were also studied, but only moderate yields were obtained (Table 1, entries 8–10). The reaction could not proceed without the copper catalyst even after 3 h of reaction time (Table 1, entry 11).

Scheme 1 Preparation of polymer-supported copper catalyst.

Table 1 Effect of solvent and catalyst for the terminal alkynes homocoupling reaction^a

Entry	Cat.	Solvent	Time/min	Yield^b(%)
a Reaction conditions: 1-ethyl-4-ethynylbenzene (1.0 mmol), n-butylamine (0.5 mmol), Cat. (5 mol% of the copper content), room temperature in air. b Isolated yield.
1	A-21·CuI	CH3OH	60	8
2	A-21·CuI	AcOEt	60	92
3	A-21·CuI	Toluene	60	95
4	A-21·CuI	CH2Cl2	60	89
5	A-21·CuI	THF	60	91
6	A-21·CuI	DMSO	60	4
7	A-21·CuI	None	10	96
8	CuI	None	20	53
9	Cu(OAc)2	None	20	66
10	CuCl2	None	20	49
11	None	None	180	—

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Subsequently, the influence of the bases on the room-temperature terminal alkynes homocoupling reaction was investigated, and the results are summarized in Table 2. As could be seen from Table 2, the reaction could not be performed without a base (Table 2, entry 1). Organic bases including primary amines, secondary amines and tertiary amines were all investigated. As can be seen from Table 2, Et₃N, DIPEA, pyridine, piperidine, tert-butylamine and tri-n-butylamine all gave the low to moderate yields of 3–47% even for 20–60 minutes reaction time (Table 2, entries 2–6 and 9). However, when we adopt n-butylamine and pyrrolidine as bases, high yields of 96% and 88% were obtained (Table 2, entries 7 and 8). Compared to these two bases, n-butylamine was chosen as the best choice for the reaction. Thus, we selected n-butylamine as the base and 5 mol% of catalyst at room temperature under solvent-free conditions in air as the optimal conditions for the terminal alkynes homocoupling reaction.

Table 2 Effect of bases for the terminal alkynes homocoupling reaction^a

Entry	Base	Time/min	Yield^b (%)
a Reaction conditions: 1-ethyl-4-ethynylbenzene (1.0 mmol), base (0.5 mmol), Cat. A-21·CuI (5 mol% of the copper content), room temperature in air. b Isolated yield.
1	None	180	—
2	Et3N	60	3
3	DIPEA	60	7
4	Pyridine	60	10
5	Piperidine	60	47
6	tert-Butylamine	60	31
7	n-Butylamine	10	96
8	Pyrrolidine	40	88
9	Tri-n-butylamine	20	4

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Under the optimized conditions obtained, we then examined the scope of the coupling reaction. A variety of terminal alkynes including aromatic and aliphatic acetylenes were tested under the optimized conditions and the results are summarized in Table 3. As shown in Table 3, phenylacetylene and the aromatic acetylenes with substituted groups in para-positions such as methyl, ethyl, n-propyl, n-butyl, fluoro, hydroxymethyl, all underwent smoothly homocoupling reactions to afford the desired corresponding products (Table 3, entries 1–7). The aromatic acetylenes bearing the electron-withdrawing groups in the meta positions are all reactive, and the yields were 90% and 98% (Table 3, entries 8 and 9). Meanwhile, the reaction could also be efficiently executed for the aliphatic alkynes but 1 mmol of base was required (Table 3, entries 10 and 11).

Table 3 Room-temperature terminal alkynes homocoupling reactions under the solvent-free conditions^a

Entry	Product	Time/min	Yield^b (%)
a Reaction conditions: terminal alkynes (1.0 mmol), n-butylamine (0.5 mmol), Cat. A-21·CuI (5 mol% of the copper content), room temperature in air. b Isolated yield. c 1 mmol n-butylamine was used.
1		10	97
2		10	96
3		10	97
4		10	96
5		10	95
6		10	97
7		10	98
8		10	98
9		20	90
10		20	85^c
11		20	89^c

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For a heterogeneous catalyst, it is important to examine its ease of separation, good recoverability and reusability. The recyclability of our polymer-supported copper catalyst A-21·CuI was also investigated. After carrying out the reaction, the mixture was diluted with CH₂Cl₂ and filtered. The catalyst was separated by simple filtration and washed with acetone several times. The catalyst was then dried under vacuum, and can be reused directly without further purification. The recovered catalyst was used in the next run, and almost consistent activity was observed for five consecutive cycles (30 min reaction time for the fourth and fifth run) (Fig. 1).

Fig. 1 Recycling experiment.

In addition, a SEM observation of the fresh catalyst and the recovered catalyst was also made, and there was no obvious change in the morphology and size of the recovered catalyst in comparison with the fresh catalyst (Fig. 2). This result revealed that the catalyst was very stable and could endure these reaction conditions. Moreover, copper leaching in the supported catalyst was also determined. ICP analysis showed that the catalyst did not show significant leaching of copper during the course of reaction. The stability and recovery of this supported catalyst A-21·CuI has also been proved by the Girard group.¹⁴

Fig. 2 Scanning electron micrograph (SEM) images of the fresh catalyst (a) and four-times reused catalyst (b).

A hot filtration test was also investigated to figure out whether the catalytic process involved in the participation of homogeneous species in equilibrium with the heterogeneous catalyst. When the neat mixture was stirred at room temperature for 5 min, CH₂Cl₂ was added and the solid catalyst quickly removed by filtration. The solution was averagely divided into two sections (S1 and S2). The corresponding product of S1 was obtained in 78% yield. Meanwhile, the neat S2 was stirred at room temperature for an additional 30 min. The reaction continued, although the conversion did not reach the level obtained in normal manner, which means that at least a part of the catalytic activity of catalyst was assigned to a homogeneous way.

In summary, we have successfully developed a novel, practical and environmentally friendly method for the terminal alkynes homocoupling reaction by using a polymer-supported copper catalyst at room temperature under solvent-free conditions. The reaction proceeded smoothly and generated the corresponding 1,3 diynes in high yields within 10–20 minutes. Moreover, this methodology offers the competitiveness of recyclability of the catalyst without significant loss of catalytic activity, and the catalyst could be readily recovered and reused for several cycles, thus making this procedure environmentally more acceptable.

Experimental section

General remarks

All chemicals were of reagent grade and used as purchased. Elemental analyses were performed on a Vario EL III recorder. ¹H NMR and ¹³C NMR spectra were measured with a Bruker Avance III 500 analyzer. GC analyses were performed on the Agilent 7890 instrument. GC/MS analyses were performed on a Saturn 2000GC/MS instrument. The copper content of the catalyst was measured by inductively coupled plasma (ICP) on a PE5300DV analyzer. Scanning electron microscopy (SEM) analyses were performed with a Hitachi S-3400N instrument.

Preparation of the polymer-supported copper catalyst

The preparation of the polymer-supported catalyst was performed according to the literature (Scheme 1). Under a nitrogen atmosphere, a round-bottomed flask was charged with Amberlyst A-21 (0.5 g), CuI (0.19 g, 1.0 mmol) and CH₃CN (5 ml). The mixture was stirred at room temperature for 24 h. Then the resulting beads were filtered, washed with CH₃CN and CH₂Cl₂, and dried under the vacuum overnight. The content of the copper was 1.31 mmol g⁻¹ as determined by inductively coupled plasma (ICP) analysis.

Typical procedure for the homocoupling reaction at room temperature under solvent-free conditions

To a round-flask containing the terminal alkyne (1.0 mmol) and n-butylamine (0.5 mmol), the supported catalyst (5 mol% of the Cu content) was added in open air. The resulting mixture was then stirred at room temperature in air for a certain time as judged by GC and GC/MS. After completion of the reaction, the mixture was diluted with CH₂Cl₂ and filtered. The filtrate was removed under reduced pressure to give the crude product. The residue was then purified by column chromatography on silica gel using petroleum ether–ethyl acetate as an eluent to afford the corresponding 1,3-diynes. All of the products are known compounds and were characterized by comparison of their spectral data with those of authentic samples.

Notes and references

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