Recent Advances in Synthetic Applications of Polyvinylpyrrolidone Supported Reagents and Catalysts

This review summarized recent progresses in the application of polyvinylpyrrolidone supported reagents and catalysts in organic synthesis.


Introduction
The use of solid-supported reagents and catalysts in solution-phase chemistry has emerged as a leading strategy that exploits the advantages of both solid-and solution-phase synthesis. The approach essentially combines the benefits of product isolation and purification in solid-phase synthesis with the high-speed development and flexible choice of chemistry from the vast repertoire of solution phase organic reactions. The organic molecules synthesis using polymer-supported reagents and catalysts is highly attractive because the work-up involves only simple filtration and evaporation of the solvent [1]. Polyvinylpyrrolidone (PVP) is an amorphous polymer having broad applications in biomedical field due to its special properties such as low toxicity and good solubility in water and most organic solvents, good adhesion characteristics, and great physiological compatibility [2]. Also, PVP has good biocompatibility and has been applied for many years as a biomaterial or additive to drug compositions, e.g. as a blood plasma expander [3].
Polyvinylpolypyrrolidone (PVPP, crospovidone, or crospolividone) is a highly cross-linked polyvinylpyrrolidone (PVP). The crosslinked form of polyvinylpyrrolidone is insoluble in water, though it still absorbs water and swells very rapidly generating a swelling force. This property makes PVPP useful as a disintegrant in pharmaceutical tablets [2]. Polyvinylpyrrolidone shows a strong binding affinity to small molecules. Furthermore, its iodine complex, povidon-iodine, is widely used as an anti-infective agent in clinical treatments [4].
Iranpoor and coworkers [5] have prepared iodine supported on polyvinylpyrrolidone (betadine) as catalysts for ring opening of epoxides and as reagent for ring opening dimerization of thiiranes in alcohols, water and acetic acid (Scheme 1). In this report, the reaction of R-(+)-styrene oxide with I 2 supported on PVP in methanol was found to be very stereospecific and the product isolated in 93% ee. In another research, Lakouraj et al. [6] described the preparation of polyvinylpyrrolidone-bromine complex (PVP-Br 2 ) as a mild and convenient reagent for selective bromination of alkenes (Scheme 2) [6].
Selective oxidation of benzyl alcohol in the presence of 2-phenylethanol was also achieved at room temperature in the presence of PVP-Br 2 (Scheme 3). In the next research, Lakouraj and Mokhtary have developed a convenient method for deprotection and direct oxidative deprotection of silylethers to the corresponding hydroxy and carbonyl compounds using polyvinylpolypyrrolidone-bromine complex (PVPP-Br 2 ) (Scheme 4) [7]. Selective oxidative deprotection of benzylic silyl ethers in the presence of primary aliphatic alcohols was also achieved at room temperature.  [10]. This solid hydrogen peroxide is found to be much safer, convenient and efficient reagent system for the ipsohydroxylation of arylboronic acids to the corresponding phenols in highyields at a faster rate (Scheme 7). The versatility of the reagent has been further expanded for the one-pot synthesis of halophenols. Lakouraj et al., [11] have demonstrated polyvinylpolypyrrolidone-phosphorous oxychloride as a versatile polymeric Vilsmeier reagent that exhibits excellent selectivity for oxygenation of sulfides to sulfoxides, and oxidation of aldehydes to carboxylic acids in the presence of hydrogen peroxide under mild reaction conditions (Scheme 8) [11]. This polymeric Vilsmeier reagent was found to retain its activity after months and is stable in a glass bottle at room temperature. Tamami and Kiasat have reported [13] a polyvinylpyrrolidonethionyl chloride complex by the reaction of thionyl chloride with two equivalents of polyvinylpyrrolidone in dichloromethane at 0 ͦ C.
The polymer-bound complex I was used for the rapid dehydration of a variety of aldoximes to produce the corresponding nitriles in high yields (Scheme 10).

Polyvinylpyrrolidone Supported Lewis Acidic Catalysts
Replacement of conventional, toxic and unstable Lewis acidic catalysts with eco-friendly reusable solid acid catalysts is an essential requirement in the development of green chemistry. For example, boron trifluoride is widely used in organic syntheses as a Lewis acid. However, boron trifluoride is highly water sensitive, irritant, and has to be used in a carefully dried apparatus. Moreover, all work must be carried out in an efficient fume hood, and its recovery from the reaction mixture results in a main source of waste, which on an industrial scale is environmentally unacceptable.
Mokhtary et al. have reported several papers on the application of the polyvinylpolypyrrolidone-bound boron trifluoride (PVPP-BF 3 ) as a stable polymeric Lewis acid catalyst in some organic reactions such as synthesis of amides by the reaction of nitriles with benzhydrol and tertiary alcohols or tert-butyl acetate via Ritter reaction (Scheme 12) [15,16], the acylation of alcohols, phenols and trimethylsilyl ethers with acetic anhydride (Scheme 13) [17], the synthesis of coumarins via Pechmann condensations of phenols with ethyl acetoacetate (Scheme 14) [18], the synthesis of 14-aryl-14H-dibenzo [a,j] xanthenes and bis(naphthalen-2-yl-sulfane) derivatives (Scheme 15) [19], the synthesis of 1,8-dioxooctahydroxanthenes and 1,8-dioxodecahydroacridines via condensation of aromatic aldehydes and dimedone in Academic Journal of Polymer science acetonitrile at room temperature, and aromatic aldehydes, dimedone, and aromatic amines in acetonitrile at 80 °C respectively (Scheme 16) [20], the oxidation of aldehydes to carboxylic acids and oxidative esterification of benzaldehydes in the presence of 35% hydrogen peroxide (Scheme 17) [21] and the oxidation of sulfides to sulfones in the presence of 35% hydrogen peroxide at room temperature (Scheme 18) [22]. Excellent yields, easy work-up and reusability and stability of the catalyst are some advantages of these methods.
Pourali and et al. prepared cross-linked polyvinylpyrrolidone supported GaCl 3 for efficient and regioselective ring-opening reaction of epoxides by various alcohols under solvent-free conditions at room temperature (Scheme 19) [23]. Furthermore, regioselective conversion of epoxides to β-azidohydrines was accomplished by sodium azide in MeOH in the presence of GaCl 3 / PVP at room temperature. GaCl 3 /PVPP is a non-hygroscopic and recoverable catalyst and is easily separated from reaction mixture by a simple filtration and reused repeatedly. Furthermore, PVPP.OTf was found to be useful as a recyclable heterogeneous catalyst for the rapid synthesis of quinoxaline derivatives (Scheme 23) [27].

Polyvinylpyrrolidone Supported Pd Catalyst
A series of poly(N-vinyl-2-pyrrolidone) immobilized Pd nanoparticles (PVP-Pd) with varying particle size have prepared by Li et al., [38] using the stepwise growth reaction. The effect of Pd particle size on the Suzuki reaction between phenylboronic acid and iodobenzene was investigated by the use of four Pd catalysts (Scheme 34). The catalytic activity of the Pd nanoparticles expressed in terms of the initial turnover frequency (moles of the biphenyl product per mole of total surface Pd atoms per min) was found to be in the order of Pd (3.9nm) > Pd (3.0nm) ~ Pd (5.2nm) > Pd (6.6nm), indicating that surface Pd atoms do not all have the same reactivity in this reaction. The general trend of increased catalytic activity with the decrease in the particle size suggests that the low-coordination number vertex and edge atoms on the particle surface are active sites for the Suzuki reaction. The lower catalytic activity for the smallest Pd nanoparticles may be due to stronger adsorption of the reaction intermediates on the particle surface, in which the strongly adsorbed species act as a poison to the reaction thereby decreasing the rate of the reaction.  In another work, Tamami et al., [39] was prepared a catalytic system based on palladium nanoparticles supported on poly(Nvinylpyrrolidone) grafted silica (Scheme 35).
The complexation of PVP-grafted silica with PdCl 2 was carried out to obtain the heterogeneous catalytic system. Transmission electron microscopy (TEM) image showed that palladium dispersed through the support in nanometer size (Figure 1). This catalytic system exhibited excellent activity in crosscoupling reactions of aryl iodides, bromides and also chlorides with olefinic compounds in Heck-Mizoraki reactions in short reaction time and high yields (Scheme 36).

Conclusion
Polymer-supported reagents and catalysts have emerged as important tools for the rapid preparation of chemical compounds in solution-phase. Clean methodologies, easy preparation of the catalysts, simple work-up procedures, good to high yields, environmentally friendly and reusable catalysts are some advantages of polyvinylpyrrolidone supported catalysts and reagents in organic multi-step synthesis. Further progresses in the development of new PVP-bound reagents, and catalysts will continue to attract innovative application of this strategy in multicomponent synthesis.