I24
Ind. Eng. Chem. Prod. Res. Dev. 1986, 25, 124-126
Use of Cross-Linked Poly(N-vinylpyrrolidone) as Solid Cosolvent Mlroslava Jefinkovl, Jaroslav Kahovec, and Frantlsek Svec. Institute of Macromolecular Chemistry, Czechoslovak Academy of Sciences, 162 06 Prague 6, Czechoslovakia
Commercial poly(N-vinylpyrrolidone) was radical-cross-linked by means of potassium peroxodisulfate at elevated temperature. The product after drying and grinding was used as solid cosolvent in a model reaction between butyl bromide and sodium phenoxide, either in a two-phase (polymer dioxane solution of reagents) or a three-phase system containing two liquid phases (polymer toluene solution of butyl bromide aqueous solution of phenoxide) or containing two solid phases and a liquid one (polymer toluene solution of butyl bromide -k solid phenoxide). Compared with N-methylpyrrolidone, the cross-linked polymer is up to 77 times more effective due to a strong "polymer effect". For the sake of comparison, linear poly(N-vinylpyrrolidone),a copolymer of N-vinylpyrrolidone with divinylbenzene, and Polyclar AT were also used, but their activity is weaker.
+
Introduction Bimolecular nucleophilic substitution reactions (SN2) are accelerated to an important degree in the presence of dipolar aprotic solvents, such as dimethylformamide, hexamethylphosphoramide, dimethyl sulfoxide, or N methylpyrrolidone (NMP), due to the selective solvation of cationic species. If the grouping of the dipolar solvent moiety is part of the polymer chain or is bound to the chain, the compounds involved are solid cosolvents which in some cases possess higher activity than their low molecular weight analogues (e.g., Janout et al., 1984ab). Although poly(N-vinylpyrrolidone)(PVP) is a massproduced, widely used ( H a d et al. 1985), and thus readily available polymeric analogue of NMP, it hownot attracted much attention yet. Yamazaki et al. (1979investigated the effect of concentration of linear PVP in a mixed solvent dioxane-ethanol on the rate of the reaction between butyl bromide and sodium phenoxide and observed a strong acceleration effect on the polymer, especially at low contents of ethanol. From the practical viewpoint, however, the use of a soluble polymer is less advantageous due to more difficult separation than a reaction performed in the presence of a polymer that is cross-linked and hence insoluble in the system and can therefore be removed by mere filtration. Cross-linked PVP was employed in the alkylation of acetoacetate enolates with alkyl sulfate in tetrahydrofuran; it was found that the presence of the polymer greatly raises the occurrence of 0-alkylation and of the E isomer (Nee and Seyden-Penne, 1982). This paper is a continuation of the preceding one (Janout et al., 1984a) and deals with an investigation of the Williamson reaction in the presence of cross-linked PVP. Experimental Technique Polymer Catalysts. Linear PVP was a common commercial product (K-90, Fluka, Switzerland), mol wt 360000. Radical-cross-linked PVP was obtained by reacting the polymer mentioned above dissolved in water (10 or 20 wt %) together with potassium peroxodisulfate (double weight with respec' to the polymer) at 80 OC for 3 h (Anderson et al., 1979). After extraction with water and methanol (each time ca. 10 h), the product contained 96-98% of the original polymer. After the product had been dried, the gel was ground to irregular particles 60-80 pm in size; if necessary, these were then separated into fractions according t~ their sizes on the corresponding sieves. Polyclar AT (G.A.F., Belgium) was a commercial product crosslinked during the polymerization catalyzed with an alkali 0196-4321/86/1225-0124$01.50/ 0
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Table I. Reaction of BuBr with PhONa in Dioxane Catalyzed by Cross-Linked PVP: Effect of Catalyst Amounta 1-(2-oxopyrrolidiny1)ethvlene units. mmol 1.0 2.0 3.0 4.0
BuBr conversion, 70 catalvst Ab catalvst B' 21.8 39.8 22.6 24.7 44.4 44.0 28.7
Reaction conditions: PhONa 2 mmol, BuBr 2.66 mmol, volume 6 mL, 50 " C , 10 h. bPrepared from 10% PVP solution. 'Prepared from 20% PVP solution.
metal at 150 "C. The copolymer N-vinylpyrrolidone-divinylbenzene (4% DVB) was prepared by radical polymerization (Morner and Longley, 1954).
Reactions Solutions of sodium phenoxide (PhONa) prepared according to Kornblum and Lurie (1959) and of butyl bromide (BuBr) in dioxane were thermostated and dosed into a reaction vessel containing PVP swollen or dissolved in dioxane (molar ratio Ph0Na:BuBr = 1:1.33). The contents of the thermostated vessel were stirred with a magnetic stirrer, and samples were taken in the course of stirring for the residual BuBr determination by gas chromatography. The results were used to calculate the conversion of BuBr. After completion of the experiment, the cross-linked polymer was filtered off, washed with dioxane and methanol, and dried. The quantity of polymer obtained always corresponded to the originally weighed amount. Results With the aim of finding suitable reaction conditions and describing the course of the reaction between PhONa and BuBr in the presence of PVP, the conversion of BuBr was measured as a dependence on the amount of catalyst obtained by the cross-linking of the variously concentrated starting solution (Table I). The reaction is a t its fastest a t the beginning; after only roughly 1 h, the conversion increases only slowly (Figure 1). Temperature has no esseiltial effect on the reaction rate, as documented by the fact that a change in the reaction temperature from 50 to 90 "C makes the conversion rise from 44% to 55.3% under conditions summarized in Table I. The reaction is relatively slow, and the size of PVP particles does not affect the reaction rate t o any considerable extent (Table 11). Table I11 summarizes the results obtained by using various types of cross-linked PVP and gives a comparison 0 1986 American Chemical
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Ind. Eng. Chem. Prod. Res. Dev., Vol. 25, No. 1, 1986
125
Table IV. Reaction of BuBr with PhONa in Toluene-Water System Catalyzed by PVP“ catalyst BuBr conversion. % none 12.4 soluble PVPb 27.3 cross-linked PVPbzC 26.2 “Reaction conditions: PhONa 2 mmol, BuBr 2.66 mol, volume 4 mL (water:toluene l : l ) , 90 “C, 10 h. b l mmol of 1-(2-0xopyrrolidiny1)ethylene units. Catalyst B.
hL 2
12
0
6
Reaction time, h
Figure 1. Kinetics of reaction of butyl bromide with sodium phenoxide in dioxane catalyzed by cross-linked poly(N-vinylpyrrolidone). Reaction conditions as in Table 11. Table 11. Reaction of BuBr with PhONa in Dioxane Catalyzed by Cross-Linked PVP: Effect of Catalyst Particle Size“ BuBr conversion, % particle size, pm 63-90 34.1 250-315 38.4 500-800 39.8 nonfractionated (63-800) 39.8
100
I
I
0
50
I
c .-
z
> 0 0
50
L 3
a Reaction conditions: catalyst B, 4 mmol 1-(2-oxopyrrolidinyl)ethylene units; for all other conditions see Table I.
100 V O ~ . % NMP
Table 111. Reaction of BuBr with PhONa in Dioxane Catalyzed by N-alkylpyrrolidones” catalvstb BuBr conversion. % efficiencv factor none 1.3 1.8 1.0 NMP linear PVP 18.6 34.6 Polyclar A T 21.5 40.4 15.0 27.4 PVP-DVB cross-linked PVP‘ 39.8 77.0 “Reaction conditions: see Table I. pyrrolidone units. Catalyst B.
b l mmol of N-alkyl-
of these results with NMP and linear PVP. The efficiency factor is defined as the ratio of the conversion of BuBr reached in the presence of polymer to that in the presence of NMP having the same bulk concentration of alkylpyrrolidone groups; both conversions have been corrected by subtracting conversion reached in the noncatalyzed reaction. The efficiency factor of cross-linked PVP attains almost twofold values compared with all the other polymers. If under the same conditions the conversion reached with NMP is to be comparable with that in the presence of PVP, the concentration of NMP in the mixture with dioxane must be raised to as much as 3.5 mol/L, as shown in the figure. If dioxane as solvent is replaced with toluene and water (a three-phase system), the reaction at 50 “C proceeds very slowly, reaching a reasonable rate only a t a higher temperature (Table IV);no difference can be observed between the soluble and cross-linked polymers. Unlike the reaction of PhONa, the accelerating effect of PVP on the reaction between KCN and BuBr is not so pronounced. In dioxane at 50 OC after 10 h of the reaction, the conversion in the absence of PVP is 32.8% while in its presence it is 43.4%. Discussion A condition of acceleration of SN2reactions is that the anion should be freed from interactions with its environment as much as possible, e.g., freed from the solvation shell. In the cases of PhONa, KCN, and other alkali salts this may be achieved by a selective solvation of the cation with dipolar aprotic solvents accompanied by the formation of a naked anion able to react quickly with alkyl
Figure 2. Rate of reaction of butyl bromide with sodium phenoxide in dioxane catalyzed by various amounts of N-methylpyrrolidone. Reaction conditions as in Table I.
halide. To obtain an efficient solvation of the cation, a relatively high concentration of the solvent (e.g., NMP) is required (Figure 2). If the N-alkylpyrrolidone grouping is part of the constitutional repeating unit of the polymer, a high number of these units is concentrated within a limited space. The molecule of a nucleophilic agent that is situated in this space is surrounded with a relatively high local concentration of the “solvent” units in spite of the low overall polymer concentration in the system. This “polymer effect” has already been described by Overberger et al. (1969) for the hydrolysis of esters catalyzed by poly(vinylimidazole). The number of interactions of groups of a polymer molecule depends, of course, on the shape of the macromolecule in solution. More extensive interactions will be reached in polymer coils with a low degree of solvation when the individual polymer segments are “concentrated” within a smaller space, i.e., in thermodynamically poorer solvents. For PVP, dioxane is just such a solvent, and the reaction therefore proceeds in this solvent in the presence of the polymer much more quickly than in a more polar solvent (Yamazaki et al., 1975). If conformational changes of a polymer molecule are limited by cross-links, solvation of the coil and hence also its swelling in a thermodynamically better solvent do not reach the level of the soluble polymer. The local concentration of N-alkylpyrrolidone units is yet higher for a cross-linked polymer than for a soluble one, and the reaction rate goes on increasing (Table 111). Two factors affect the Faction course in the case of cross-linked PVP. First, the .ase contact between N-alkylpyrrolidone units and nucle 2hile increases with decreasing swelling and thus with the increasing degree of cross-linking. This is documented by the higher conversion reached with catalyst B, which swells in water to 4.6 times its dry volume, while catalyst A swells to 5.2 times its volume. Second, however, the increasing network density restricts the accessibility of functional groups of the polymer to reaction components. This is also why the more strongly cross-linked 8
Ind. Eng. Chem. Prod. Res. Dev. 1966, 25, 126-128
126
Polyclar AT with 2.1 degree of swelling does not possess such a pronounced acceleration effect compared with catalyst B. In the case of the copolymer with DVB the negative effect of the inert cross-linking agent comes into play, reducing the concentration of N-alkylpyrrolidone units in the vicinity of the reaction site. In addition to its activity as a solid cosolvent, the cross-linked PVP also possesses the ability to catalyze phase transfer, as documented by the reaction in the toluene-water system. Due to an interaction between the cation and N-alkylpyrrolidone units of the swollen polymer in the aqueous phase, the phenoxide ion too may be transferred into the organic phase. A mechanism alternative to complexation is micellar microhomogenization of both immiscible phases near N-alkylpyrrolidone groupings in the polymer matrix. Another example is catalysis of the reaction between BuBr and KCN which is insoluble in dioxane. In the reaction of 1.33 mmol of BuBr, 2.66 mmol of KCN, and 1 mmol (0.111 g) of cross-linked PVP (catalyst B), the conversion of BuBr a t 50 “C after 10 h is 43.470, while under similar conditions but in the absence of PVP it is 32.8%.
The results reported above show that the radicalcross-linked PVP is not only an efficient solid solvent whose activity is several times higher than that of both NMP and soluble PVP, but also a phase-transfer catalyst active in liquid-solid-liquid and solid-liquidsolid systems. Registry No. KCN, 151-50-8;PhONa, 139-02-6;BuBr, 10965-9;PVP (homopolymer),9003-39-8;potassium peroxodisulfate, 7727-21-1. Literature Cited Anderson, C. C.; Rodriguez, F.; Thurston, D. A. J. Appl. Polym. Scl. 1979, 23, 2453. Haaf, F.; Sanner, A.; Straub, F. Polym. J, (Tokyo) 1985, 77, 143. Janout, V.; Kahovec, J.; Hrudkov6, H.;Svec, F.; Cefelin, P. Poly” Bull. (6erlln) 1984, 11, 215; Janout, V.; Hrudkovi, H.; Cefein, P. Collect. Czech. Chem. Commun , 1984, 49, 1563. Kornblum, N.; Lurie, A. P. J. Am. Chem. SOC.1959, 81, 2705. Morner, R. R.; Longley, R. I. U S . Patent 2676949, 1954. Nee, G.;Seyden-Penne, J. Tetrahedron 1982, 38, 3485. Overberger. C. G.; Morimoto, M.; Chou, I.; Salamone, J. C. Macromolecules 1989, 2, 553. Yamazaki, N.; Hirho, A.; Nakahama, S. Polym. J. (Tokyo) 1975, 7 , 402.
Received for review September 25, 1985 Accepted October 22, 1985
COMMUNICATIONS Reduction of Solutes Hydrolysis by Anion Exchangers
Extension of work done previously on the reduction of the hydrolysis of niacinamide dissolved in water by anion exchangers of the OH- form is described. I n a previous study it was found that by the use of the same anion exchanger on the : 0 C cycle, the hydrolysis had been reduced by 1 order of magnitude. The present study dealt with aqueous solutions of acetamide. acetonitrile, and propiononitrile and reached essentially the same conclusion reached before for niacinamide.
BCONHz
Introduction
Several processes for synthesizing amides start with the corresponding nitriles and by hydrolysis convert the nitriles to the corresponding amide. In the practical process one can expect to get the maximum conversion of the nitrile to the amide, but since the amide can further undergo hydrolysis to the corresponding ammonium salt, the reaction effluent can contain all three species, the starting nitrile, the desired amide, and the byproduct ammonium salt A-CN
+H20 __+
A-CONH,
+H20
A-COONH,
(1)
where A can be any relevant group. Thus the reaction product, which is an aqueous solution, as the feed, will contain cations (i.e., NH,’), anions (i.e., the corresponding carboxylate anion), and nonionic solutes (i.e., the desired amide). An easy way to get rid of the ions is by conventional ion-exchange process. Thus, in the case of niacinamide one would expect that passing niacinamide and ammonium nicotinate in aqueous solution through ion-exchange train would result in a pure amide 0196-4321/86/1225-0126$01.50/0
+ BCOONHI + R-H BCONH2
BCONHz
+ BCOOH + R’OH
+
+ BCOOH + RNH4
+
BCONHz
+ BCOOR’ + H2O
(2) (3)
where B is 3-pyridyl, R is the immobile part of the cation exchanger, and R’ is the immobile part of the anion exchanger. However, when the above-mentioned process was carried out, it was found that the effluent solution of reaction 3 still contained BCOONH,. Further investigation revealed that reaction 3 is not as simple as written since another side reaction is involved, i.e., the hydrolysis of the amide by the R O H resin:
BCONH,
+ HZO
ROH
BCOONH,
(4)
The BCOO- part of the resulting ammonium salt may be caught by the R’OH resin (see (5)), but since the ion exBCOONH,
+ R’OH
-
BCOOR
+ NH40H
(5)
change is done on a column, some leak of the hydrolysis product, especially that hydrolysis occurring in the lower part of the column (assuming downflow), is unavoidable. 0 1986 American Chemical Society
