Polystyrene-bound dimethylaminopyridine (PS-DMAP)

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(N-benzylmethylaminopyridine polymer bound; N-methyl-N-(4-pyridyl)aminomethyl-polystyrene cross-linked with divinylbenzene; reagent used as recyclable catalyst for acylation reactions)

Form Supplied in: 2-4% cross-linked poly(styrene-co-divinylbenzene) as resin type; commercially available.

Analysis of Reagent Purity: typical loading 2.5-3.0 mmol N g-1 (dry).

Preparative Methods: several syntheses for typical polymeric forms of (dimethylamino)pyridine have been published: (i) Condensation reaction of laurylated poly(ethyleneimine) with 3-[N-methyl-N-(4-pyridyl)amino]propionic acid.1 (ii) Substitution reaction of polystyrene bearing (methylamino)methyl substituents with 4-chloropyridine.2 (iii) Copolymerization of 4-(N-methyl-N-para-vinylbenzylamino)pyridine, styrene and commercially available divinylbenzene (DVB).3 (iv) Chemical modification of halogenated bead polymers such as chloromethylstyrene copolymer with 4-(N-methylamino)pyridine.4

Introduction

Polystyrene-bound dimethylaminopyridine (PS-DMAP) is a polymer-bound equivalent of 4-(dimethylamino) pyridine (DMAP)5 which may be used as a catalyst for acylation and related reactions. PS-DMAP can be recovered easily from the reaction mixture and is recyclable. Therefore, PS-DMAP can be used in flow systems such as packed or fluidized bed reactors.

Acylations

The application of PS-DMAP as a catalyst for the acylation of hydroxy groups with acid anhydride has been investigated, in particular for acetic anhydride. Catalytic PS-DMAP accelerates the acylation of sluggish nucleophiles, e.g. tertiary alcohols. The catalytic activity of PS-DMAP for the acylation of linalool (1)3,6 and 1-methylcyclohexanol4,7,8 with acetic anhydride has been studied.

Although the acetylation is hardly catalyzed by triethylamine alone, it proceeds easily in the presence of PS-DMAP.3 The activity of PS-DMAP, cross-linked with 2 mol % divinylbenzene (DVB), is slightly lower than that of DMAP. In this reaction, the catalyst is recovered by filtration, washed with aqueous sodium hydroxide and acetone, and the recovered PS-DMAP can be reused without a significant reduction in catalytic activity.

The reaction mechanism suggests that the catalytic activity of DMAP moiety is due to both the increased electron-donating ability of the ring nitrogen and the increased stability of the acetylpyridinium species.1a,3,6

PS-DMAP can also be used for O-acetylation of enols (2), O-formylation (3), O-silylation (4), N-acetylation (5), and O-tritylation (6) in the same manner as DMAP under homogeneous conditions.4a Generally, the yields in the two-phase system are somewhat lower than those in the homogeneous environment.

Esterifications

PS-DMAP beads act as a catalyst for ester syntheses by the dicyclohexylcarbodiimide (DCC) method (7)2, in the transesterification of para-nitrophenyl active ester (8)4a and in the esterification with dialkyl dicarbonate (eqs 9 and 10).9

In the esterification of benzoic acid with MeOH by the DCC method, the process catalyzed by the polymer-bound reagent is relatively slow and the yield is lower than with DMAP under homogeneous conditions (7). Transesterification of para-nitrophenyl active ester with methanol proceeds in quantitative yield.

In the esterification of N-protected amino acids using dimethyl dicarbonate (9) and diallyl dicarbonate (10) as reagents, the use of PS-DMAP leads to product formation in satisfactory yield and optical purity, although a longer reaction time is required than in the case of DMAP catalyst.9

Application of PS-DMAP as a Storable Acylium Repository for Amide, Ester and Thioester Formations10,11

PS-DMAP may also be used as a stoichiometric polymer-bound acylium repository for N-substituted acyl pyridinium salts derived from acid chlorides, and a variety of acyl derivatives, including esters, amides, and thioesters can be synthesized in this way. The electrophilic component is reacted with PS-DMAP and an acyl pyridinium salt forms which is then reacted with various nucleophiles such as alcohols, amines, and thiols without addition of a tertiary amines base (11, 1). This condensation reaction can also be used for sulfonamide and phosphonamide syntheses.

The key to this approach is the ability to purify the polymer-bound acylium salt by solvent washes. When the nucleophile is used as the limiting reagent, the product is isolated in high purity by filtration, with the excess electrophile remaining bound to the resin.

PS-DMAP and isobutyl chloroformate act as a polymeric activating agent for carboxylic acids to form the mixed carbonic-carboxylic anhydride, which may then acylate nucleophiles after polymer removal (12).10,11

Related Reagents.

4-(Dimethylamino)pyridine (DMAP).


1. (a) Hierl, M. A.; Gamson, E. P.; Klotz, I. M., J. Am. Chem. Soc. 1979, 101, 6020. (b) Delaney, E. J.; Wood, L. E.; Klotz, I. M., J. Am. Chem. Soc. 1982, 104, 799.
2. Shinkai, S.; Tsuji, H.; Hara, Y.; Manabe, O., Bull. Chem. Soc. Jpn. 1981, 54, 631.
3. Tomoi, M.; Akada, Y.; Kakiuchi, H., Macromol. Chem., Rapid Commun. 1982, 3, 537.
4. (a) Menger, F. M.; McCann, D. J., J. Org. Chem. 1985, 50, 3928. (b) Deratani, A.; Darling, G. D.; Horak, D.; Fréchet, J. M. J., Macromolecules 1987, 20, 767.
5. Höfle, G.; Steglich, W.; Vorbrüggen, H., Angew. Chem., Int. Ed. Engl. 1978, 17, 569.
6. Tomoi, M.; Goto, M.; Kakiuchi, H., J. Polym. Sci. Part A, Polym. Chem. 1987, 25, 77.
7. Keay, J. G.; Scriven, E. F. V., Chem. Ind. 1994, 53, 339.
8. Guendouz, F.; Jacquier, R.; Verducci, J., Tetrahedron 1988, 44, 7095.
9. Takeda, K.; Akiyama, A.; Nakamura, H.; Takizawa, S.; Mizuno, Y.; Takayanagi, H.; Harigaya, Y., Synthesis 1994, 1063.
10. Shai, Y.; Jacobson, K. A.; Patchornik, A., J. Am. Chem. Soc. 1985, 107, 4249.
11. Patchornik, A., Chemtech. 1987, 17, 58.

Kazuyoshi Takeda

Ebara Research Co. Ltd., Fujisawa-shi, Japan



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