Sulfated tungstate catalyzed hydration of alkynes

A heterogeneous catalyst based on sulfated tungstate has been developed for the environmentally benign hydration of alkynes to the corresponding ketones in high yields (84-95%). Attractive features of the protocol are its generality, as evidenced by its successful application to alkyl and aryl alkynes with variable functionalities, mild and solvent free conditions, easy product isolation and reusability of the catalyst.


Introduction
The catalytic hydration of alkynes, leading to the formation of aldehydes and ketones is of considerable interest because of availability of alkynyl substrates and the fundamental importance of aldehydes and ketones for bulk and fine chemical industries.Alkyne hydration has been employed in the synthesis of active pharmaceutical ingredients, such as azaperone, benperidol, droperidol and fexofenadine.The hydration of terminal alkynes can give either a methyl ketone (Markovnikov addition) or an aldehyde (anti-Markovnikov addition), however, in most of the cases Markovnikov addition occurs giving methyl ketones exclusively.Classical approaches, towards hydration of alkynes, use HgO-H2SO4 1,2 and HgO-BF3 3,4 as catalysts and need strong acidic conditions but mercury toxicity and the requirement of strong acids are major drawbacks of these approaches.Brønsted acids, 5 various transition metals including Pd, 6 Ir, 7 Pt 8 and Fe, 9 have been examined as catalysts and were viable for the hydration.Gold complexes 10,11 have also been employed and require, in many cases, silver salts 12 as a co-catalyst to enhance the catalytic activity.Recently, AgSbF6 catalyzed hydration of alkynes has been reported. 13All these systems have drawbacks, predominantly high cost of the metals, recovery and reuse of catalysts, and use of strong acids as co-catalysts, which may cause chemoselectivity and substrate compatibility problems.
Heterogeneous catalysts have received attention as green catalysts because of their inherent advantageous ease of recovery and potential for recyclability.Kobayashi and co-workers have reported hydration of 4-ethynyltoluene over alkylated polystyrene supported sulfonic acid using a catalytic amount of Brønsted acid. 14However, the catalytic activity was low and method is limited to 4-ethynyltoluene only.Recently, AuI containing mesoporous silica 15 catalyzed hydrations of alkynes, including aromatic and aliphatic alkynes, have been disclosed.Although, this catalyst showed high efficiency, it still requires H2SO4 as co-catalyst.With these limited methods, and many drawbacks, there is scope for newer, especially greener, methods.
Recently, we introduced sulfated tungstate as a mild solid acid and placed it above silica in acidity and demonstrated its effectiveness as a green catalyst for many reactions including amidation, 16 transamidation, 17 Ritter reaction, 18 N-formylation, 19 Biginelli, 20 Kindler, 21 Willgerodt-Kindler, 22 Strecker reactions 23 and N-alkylations. 24Attributes of sulfated tungstate are its ease of preparation, mild acidity, stability, and reusability.These attributes encouraged us to further explore and expand its applications to firmly establish its versatility.Herein, investigations related to its potential as a catalyst for the hydration of alkynes to form methyl ketones are disclosed.

Result and Discussion
Preliminary investigations to study the suitability of sulfated tungstate as a catalyst for hydration of alkynes and optimization of reaction conditions involved the use of phenylacetylene as model substrate (Scheme 1).Scheme 1. Hydration of phenyl alkyne using sulfated tungstate.
Investigations were carried out to establish the catalytic role of sulfated tungstate and to optimize the reaction conditions (Table 1).Reactions were carried out under solvent free conditions, both in the presence and absence of sulfated tungstate.In the presence of the catalyst (20 wt%) at 100 °C after 3 h phenylacetylene was converted to acetophenone in 95% yield, but in the absence of catalyst the reaction did not proceed in 12 h and the substrate remained unreacted, thus establishing the catalytic role (Table 1, entries 1 and 5).Further experiments to optimize the quantity of sulfated tungstate needed to find that 20 wt% was sufficient to produce in 3 h the product in an isolated yield of 95% (Table 1, entries 2-7).When higher percentages were used stirring the reaction mixture became increasingly difficult and at 100% almost all substrate adsorbed on the catalyst leading to erratic results.Experiments were also carried out at room temperature, 60 and 80 °C, using 20 wt% of the catalyst.The reaction failed to occur at room temperature (Table 1 entry 6) and yields declined to 41 and 66% at 60 and 80 °C, respectively (Table 1, entries 7 and 8).Since water is a reactant, an experiment was carried out in the presence of excess of water and the yield remained unaffected indicating that the water quantity used in the initial experiments was adequate.As regards the use of solvent, reactions were carried out in ethanol, ethyl acetate and toluene.All the solvents were suitable but gave relatively lower yields, which could be attributed to lower reaction temperatures in case of ethanol and ethyl acetate (Table 1, entries 9 and 12) and the limited water solubility in toluene (Table 1, entry 15).Experiments with higher loading of catalyst were possible in solvents and the results with 50 and 100 wt% are included in Table 1.In all cases with higher catalyst loading yields were lower with substrate remaining unreacted (Table 1, entries 9 to 17).To establish the scope of the protocol, various aromatic and aliphatic alkynes were examined (Table 2).All the substrates were efficiently converted into the corresponding methyl ketones in moderate to high yields.Aromatic substrates carrying various electron donating or withdrawing groups at para or meta positions underwent reaction smoothly to the corresponding carbonyl compounds in moderate to high yields, indicating that substituents have no influence on the reaction outcome (Table 2, entries 2-9).Aliphatic terminal alkynes such as 4-pentyn-1-ol and prop-2-ynyl benzoate can also be hydrated but these reactions were slow and required longer reaction times to achieve adequate yields of the expected products (Table 2, entries 10 and 11).A reaction was attempted with diphenylacetylene, a substrate with an internal alkyne, but it was unreactive (Table 2, entry 12).The failure of diphenylacetylene (internal alkyne) to react was tentatively attributed to its non polar nature and higher stability owing to extended conjugation.
The work-up procedure was simple; sulfated tungstate was filtered off after diluting the reaction mixture with ethyl acetate, followed by concentration and purification by chromatography.A catalyst reusability study was performed, by recycling the catalyst after isolation and drying, without makeup of the handling losses which stood at <5%, and the catalyst was stable and reusable four times without any significant loss of activity with marginal drop in yield from 95% with fresh catalyst to 91% after a fourth recycle.
To show that the reaction is heterogeneous, a standard metal leaching experiment was conducted by hot filtration method.Two sets of experiments were conducted and both reactions proceeded for 30 min.One experiment was worked up, while from the other, the catalyst was filtered off and the reaction was continued at the same reaction temperature of 100 °C for 3 h and worked up.The yields obtained in both cases, 16 and 18%, respectively, were practically the same, indicating that no homogeneous catalysis was involved.

Conclusions
In conclusion, sulfated tungstate has been established as a highly efficient mildly acidic heterogeneous catalyst for the hydration of terminal alkynes.This new protocol has advantages of catalyst reusability, solvent-free conditions, and easy workup procedures, thus scoring high on eco-friendliness.

Experimental Section
Reagents.All chemicals were purchased from Spectrochem Pvt. Ltd.India and were used without further purification.Preparation of sulfated tungstate 16 Anhydrous sodium tungstate (32.9 g, 0.1 mol) was added portion wise, maintaining the temperature between 0 to 5 °C, to a stirred solution of chlorosulfonic acid (23.2 g, 0.2 mol) in chloroform (150 mL) contained in a 250 mL round bottom flask fitted with CaCl2 drying tube, placed in an ice bath.After completion of addition, the mixture was stirred further for 1 h.The pale yellow solid obtained was filtered, washed repeatedly with deionized water until filtrate was neutral and free from chloride ions (detected by AgNO3 test) and dried in an oven for 2 h at 100 °C to get sulfated tungstate (33 g, 86% w/w).General procedure for hydration of phenylacetylene (Table 2, entry 1).Sulfated tungstate (0.20 g, 20 wt%) was added to a mixture of phenylacetylene (1.00 g, 9.79 mmol) and water (0.74 g, 39.16 mmol) and the resulting suspension was stirred at 100 °C.The progress of the reaction was monitored by TLC.After the completion of the reaction, the reaction mixture was cooled,

Table 1 .
Results of optimisation studies a b Isolated yield.c Bold indicates optimum conditions used in subsequent studies.

Table 2 .
Hydration reactions of various alkynes in the presence of sulfated tungstate a Reaction conditions: Phenylacetylene (1 equiv.),water (4 equiv.)and sulfated tungstate (20 wt%) under solvent free at 100 °C.b Isolated yield.c All products are known and were identified by their melting point (if any), IR and 1 H-NMR spectra as per literature.d NR = No reaction. a