SnCl₄·5H₂O: A Highly Efficient Catalyst for Hydration of Alkyne

Abstract

SnCl₄·5H₂O is a highly efficient catalyst in the hydration of terminal alkynes that affords carbonyl compounds in high to good yields. Under the optimized reaction conditions, the moderate to excellent yields of corresponding ketones were obtained when the aromatic and aliphatic terminal alkynes were used as substrates. With using diphenylacetylene as an internal alkyne, the corresponding ketone was not detected in the reaction mixture.

1. Introduction

The hydration of alkyne is one of the most important methods for the synthesis of ketone (Scheme 1) [1,2]. The addition of water to the alkyne, with a perfect atom economy, is regarded as a convenient and efficient access to carbonyl compound in modern organic synthesis [3,4].

Scheme 1. The hydration of alkyne.

Scheme 1. The hydration of alkyne.

The classical methods for the hydration of alkynes have been carried out using mercury (II) salts as Lewis acidic catalysts in aqueous sulfuric acid [5]. However, the toxicity of mercury (II) and the requirement of strong acid have produced pollution problems that have limited its applications [6]. As possible alternative catalysts, transition-metal complexes containing Rh [7], Ir [8], Pb [9], Pt [10], Au [11,12,13,14,15,16], Ag [17,18], Fe [19], Co [20] have been reported to catalyze the hydration of alkyne in good yields. At the same time, anti-Markovnikov hydration of terminal alkyne have been carried out in the presence of ruthenium complex [21,22]. It was noted that the strong Brønsted acid such as TfOH or Tf₂NH [23] or concentrated H₂SO₄ [24], HCO₂H [25] or PTSA [26] has to be used as a cocatalyst in order to obtain a good yield of ketone when the transition-metal complex was employed as a catalyst in the hydration of alkyne. Recently, it was found that the metal salts were effective at activating the carbon-carbon triple bond in the presence of protonic acids, for instance, In(OTf)₃ with PTSA [27], FeCl₃ with AcOH [28] and FeCl₂·4H₂O with MsOH [29]. These methods use non-noble metal salts as catalysts, but the stoichiometric amount of Brønsted acid as a cocatalyst was still necessary for the hydration of alkyne. Therefore, the development of a general, efficient, inexpensive and readily available catalyst for the hydration of alkyne to corresponding carbonyl compound is very much in demand [30,31,32,33].

It is well known that SnCl₄ is a common, cheap, easy-handling Lewis acid, and has much lower toxicity. Recently, as a Lewis acid catalyst, SnCl₄ has been used widely in reduction of glycopyranosyl azides [34], the ring-opening reaction of 4, 5-dihydropyrroles [35], conversion of glucose [36] and intermolecular polyene cyclization [37]. In this work, we found that SnCl₄·5H₂O was a highly efficient and environmentally benign catalyst for the hydration of terminal alkyne to generate methyl ketone without using liquid Brønsted acid as a cocatalyst. To the best of our knowledge, this is the first example of Sn-catalyzed hydration of alkyne. In this manuscript, the reaction conditions and the substrate scope of hydration of alkyne were investigated when SnCl₄·5H₂O was employed as a catalyst.

2. Results and Discussion

2.1. Effects of Varying the Catalyst

Initially, the catalytic activity of transition metal salt was investigated in the hydration of phenylacetylene (1a) when using MeOH as a solvent, and the results are listed in Table 1.

Table 1. Hydration of phenylacetylene catalyzed by transition metal salt ^a.

Entry	Catalyst	Yield b %
1	CuCl	15
2	CuCl2·2H2O	31
3	Cu(NO3)2·3H2O	26
4	FeCl3	4
5	SnCl2·2H2O	66
6	SnCl4·5H2O	70
7 c	SnCl4·5H2O	91

^a Reaction conditions: phenylacetylene (2 mmol), catalyst (10 mol %), MeOH (1 mL), reaction temperature 120 °C, reaction time18 h; ^b GC yield; ^c 15 mol % of catalyst was used.

Table 1. Hydration of phenylacetylene catalyzed by transition metal salt ^a.

Entry	Catalyst	Yield b %
1	CuCl	15
2	CuCl2·2H2O	31
3	Cu(NO3)2·3H2O	26
4	FeCl3	4
5	SnCl2·2H2O	66
6	SnCl4·5H2O	70
7 c	SnCl4·5H2O	91

^a Reaction conditions: phenylacetylene (2 mmol), catalyst (10 mol %), MeOH (1 mL), reaction temperature 120 °C, reaction time18 h; ^b GC yield; ^c 15 mol % of catalyst was used.

It is shown in Table 1 that acetophenone (2a) was given in 15% yield when the 10 mol % of CuCl was used as a catalyst in MeOH at 120 °C for 18 h (entry 1), and the better yield of acetophenone (2a) was obtained when the Cu²⁺ salts were used as catalysts (entries 2 and 3). It was probably due to the Lewis acid property of Cu²⁺. The same tendency was found when different valence states of stannic salts were used as catalysts in the hydration of phenylacetylene (1a) (Table 1, entries 5 and 6). In the presence of SnCl₂·2H₂O, the acetophenone (2a) was yield to 66%. The yield of acetophenone (2a) was increased to 70% when employing SnCl₄·5H₂O (10 mol %) as a catalyst for the hydration of phenylacetylene (1a). When the amount of SnCl₄·5H₂O was increased to 15 mol %, the yield of product was increased to 91% (Table 1, entry 7). However, when using FeCl₃ with the strong Lewis acidity as a catalyst, only 4% of acetophenone (2a) was obtained (Table 1, entry 4), which could be caused by the strong and hard Lewis acidity of FeCl₃ [26].

2.2. Optimum Reaction Conditions

The effect of solvent on the hydration of phenylacetylene (1a) was also investigated by screening different solvents, and the results showed that the solvent played a key role in this process (Table 2, entries 1–9). When the reaction was carried out in 1,4-dioxane or DMF, a trace amount of acetophenone (2a) was detected in the reaction mixture (Table 2, entries 1 and 2). Other common solvents such as toluene, DMSO, CH₃CN, DCM and acetone gave moderate yield of acetophenone (2a) (Table 2, entries 3–7). When the methanol with active proton was used as a solvent for the hydration of phenylacetylene (1a), the yield of acetophenone (2a) was increased to 91%, respectively. It was noted that the addition of water in solvent did not accelerate this reaction, and the yield of acetophenone (2a) was decreased slightly swhen the mixture of methanol and water was used as a solvent (Table 2, entry 10). When using ethanol alternative methanol, a similar yield of acetophenone (2a) was obtained (Table 2, entry 8). This indicates that protic solvent could accelerate the hydration of alkyne.

Table 2. Optimization of solvents and reaction conditions for the hydration of phenylacetylene ^a.

Entry	Solvent	Temperature °C	Time h	Yield b %
1	1,4-dioxane	120	18	1
2	DMF	120	18	<1
3	Toluene	120	18	46
4	DMSO	120	18	49
5	CH3CN	120	18	37
6	DCM	120	18	42
7	CH3COCH3	120	18	66
8	EtOH	120	18	90
9	MeOH	120	18	91
10 c	MeOH	120	18	84
11	MeOH	110	18	60
12	MeOH	130	18	90
13	MeOH	120	14	80
14	MeOH	120	16	88
15	MeOH	120	20	90

^a Reaction conditions: phenylacetylene (2 mmol), SnCl₄·5H₂O (15 mol %), solvent (1 mL); ^b GC yield; ^c 2 mmol H₂O was added in the reaction mixture.

Table 2. Optimization of solvents and reaction conditions for the hydration of phenylacetylene ^a.

Entry	Solvent	Temperature °C	Time h	Yield b %
1	1,4-dioxane	120	18	1
2	DMF	120	18	<1
3	Toluene	120	18	46
4	DMSO	120	18	49
5	CH3CN	120	18	37
6	DCM	120	18	42
7	CH3COCH3	120	18	66
8	EtOH	120	18	90
9	MeOH	120	18	91
10 c	MeOH	120	18	84
11	MeOH	110	18	60
12	MeOH	130	18	90
13	MeOH	120	14	80
14	MeOH	120	16	88
15	MeOH	120	20	90

^a Reaction conditions: phenylacetylene (2 mmol), SnCl₄·5H₂O (15 mol %), solvent (1 mL); ^b GC yield; ^c 2 mmol H₂O was added in the reaction mixture.

In this work, the effect of reaction temperature on the hydration of alkyne was evaluated. When the reaction temperature was decreased to 110 °C, the yield of acetophenone (2a) was decreased to 60% (Table 2, entry 11). Increasing the reaction temperature to 130 °C did not improve the yield of acetophenone (2a), which indicates that 120 °C was the optimal reaction temperature (Table 2, entry 12). The yield of acetophenone (2a) was increased with prolonging the reaction time, but the yield was not further improved when the reaction time was increased more than 18 h. The acetophenone (2a) was yield to 90% when the reaction time was prolonged to 20 h (Table 2, entry 15).

2.3. Hydration of Other Alkynes

Under the optimal reaction conditions, the scope and limitation of the hydration with SnCl₄·5H₂O were investigated with using a series of terminal aromatic alkynes with different substituent groups on the aromatic ring, aliphatic alkynes, and internal alkyne as substrates, and the results are listed in Table 3.

Table 3. Hydration of other alkynes using SnCl₄·5H₂O as a catalyst ^a.

Entry	Alkyne	Product	Yield b %
1	(1a)	(2a)	91 c
2	(1b)	(2b)	98
3	(1c)	(2c)	93
4	(1d)	(2d)	>99
5	(1e)	(2e)	49
6	(1f)	(2f)	81
7	(1g)	(2g)	-

^a Reaction conditions: alkyne (2 mmol), SnCl₄·5H₂O (15 mol %), MeOH (1 mL), reaction temperature 120 °C, reaction time 18 h; ^b1HNMR yield; ^c GC yield.

Table 3. Hydration of other alkynes using SnCl₄·5H₂O as a catalyst ^a.

Entry	Alkyne	Product	Yield b %
1	(1a)	(2a)	91 c
2	(1b)	(2b)	98
3	(1c)	(2c)	93
4	(1d)	(2d)	>99
5	(1e)	(2e)	49
6	(1f)	(2f)	81
7	(1g)	(2g)	-

^a Reaction conditions: alkyne (2 mmol), SnCl₄·5H₂O (15 mol %), MeOH (1 mL), reaction temperature 120 °C, reaction time 18 h; ^b1HNMR yield; ^c GC yield.

From Table 3, it can be seen that liquid aromatic alkynes were efficiently converted to the corresponding ketones. Electron rich aromatic alkynes (Table 3, entries 2–4) showed better conversion in comparison to alkyne that contain electron withdrawing group (Table 3, entry 5). When 4-fluorophenylacetylene was used as a substrate, the corresponding ketone was yield to 49%. The results in Table 3 also indicate that the steric hindrance of substituent on benzene had very little influence on the catalytic efficiency in the hydration of terminal aromatic alkynes, and a substituent on the m-position of benzene, with more steric hindrance, showed 98% yields for the corresponding product (Table 3, entry 2). To our delight, not only aromatic alkyne, but also aliphatic alkyne (Table 3, entry 6) was converted effectively to the corresponding aliphatic ketone in 81% yield.

Hydration of internal alkyne was also investigated under the optimal reaction conditions. Unfortunately, the corresponding ketone was not found (Table 3, entry 7) in the reaction mixture.

2.4. Possible Reaction Mechanism

Based on previous reports [38,39] and the results in our study, a probable catalytic cycle was proposed for the hydration of alkyne using SnCl₄·5H₂O as a catalyst, as shown in Scheme 2. Generally, the hydration of alkyne may follow pathways: one is proposed based on Hg²⁺ salts as catalysts and another is proposed using Brønsted acids as catalysts. Sn⁴⁺ salts show strong Lewis acidity, so SnCl₄ could form hydrates with water and the proton in H₂O was activated. In this process, the carbon-carbon triple bond of alkyne was protonated by H⁺ which was produced by the activated H₂O which was contained in solvent and catalyst and then coordinated with SnCl₄(H₂O)OH⁻ to form intermediate II. Then intermediate II was reductive elimination and rapid tautomerization to produce methyl ketone.

Scheme 2. The possible mechanism for the hydration of alkyne in the presence of SnCl₄·5H₂O.

Scheme 2. The possible mechanism for the hydration of alkyne in the presence of SnCl₄·5H₂O.

3. Experimental Section

3.1. Chemicals

All the chemicals were commercially available and were used without further purification. ¹H NMR spectra were recorded on a Bruker 400 MHz instrument using 0.5 mL CDCl₃ as solvent containing TMS as internal standard. The products were analyzed by a HP 6890/5973 GC-MS and a gas chromatography (GC, Techcomp, 7900; Techcomp Ltd.: Shanghai, China) equipped with a flame-ionized detector (FID).

3.2. Hydration Reaction

General procedure for hydration of alkyne: The SnCl₄·5H₂O (0.3 mmol, 15 mol %) and phenylacetylene (1a, 2 mmol) were added to 1 mL methanol in a 25 mL sealed tube. The reaction mixture was heated up to 120 °C and stirred at refluxed for 18 h. After completion of the reaction, the crude mixture was allowed to cool at room temperature and filtered through celite to give acetophenone (2a) as yellow filtrate. The products were qualitatively analyzed by a HP 6890/5973 GC-MS and quantificationally analyzed by a gas chromatography (GC, Techcomp, 7900; Techcomp Ltd.: Shanghai, China) equipped with a flame-ionized detector (FID) or a Bruker 400 MHz instrument with using 0.5 mL CDCl₃ as solvent containing TMS as internal standard.

4. Conclusions

In summary, a general, efficient and non-noble metal method using SnCl₄·5H₂O as a catalyst without using Brønsted acid as a cocatalyst for the transformation of various alkynes to the corresponding ketones in high yields has been successfully developed. Under optimized reaction conditions, substrates with electron-withdrawing groups or electron-donating groups were performed smoothly and gave moderate to excellent yields. It should be noted that aliphatic alkyne also afforded the ketone in good yield.