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Synlett 2003(1): 0115-0117
DOI: 10.1055/s-2003-36239
LETTER
© Georg Thieme Verlag Stuttgart · New York

Polymer-Supported DMI as a Potential Heterogeneous Dehydrating Agent: Application to Esterification and Amidation

Wannaporn Disadee, Toshiko Watanabe, Tsutomu Ishikawa*
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan
Fax: +81(43)2902910; e-Mail: benti@p.chiba-u.ac.jp;
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Publication History

Received 7 October 2002
Publication Date:
18 December 2002 (online)

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Abstract

A new polymer-supported urea (P-DMI) (4) was prepared as a precursor for a new heterogeneous dehydrating agent, polymer-supported chloroamidinium chloride (P-DMC) (5). Application of 4 to esterification and amidation, after conversion to 5, efficiently afforded dehydrated products. No epimerization was practically observed in peptide synthesis. Compound 4 (P-DMI) was recovered as a re-useable form by simple filtration.

Key words

polymer-supported reagent - esterification - amidation - peptide synthesis - recyclability

4

Reaction time can be shortened from 3 d to 1 d by use of the corresponding iodide in place of the 4-chloromethyl polystyrene resin.

5

Conversion of the starting polystyrene derivative to P-DMI (4) was estimated by relative peak ratio between carbonyl (at δ = 162 ppm) and aromatic carbon absorptions (at δ = 128 ppm) in the product using solid 13C NMR technique, in addition to combustion analysis. Details will be reported elsewhere.

6

Typical Procedure (entries 2 and 3 in Table 1):
A mixture of P-DMI(4) (984 mg) and oxalyl chloride
(1.71 mmol) in benzene (10 mL) was refluxed for 24 h, cooled to r.t. and evaporated in vacuo to yield crude P-DMC (5) (1.19 g, 88% conversion).
To a suspension of crude 5 (1.19 g), dihydrocinnamic acid (1.0 mmol) in CH2Cl2 (10 mL) were added t-butyl alcohol (1.0 mmol) and Et3N (5.0 mmol), and then the suspension was stirred at r.t. for 48 h. The polymer was recovered by filtration and washing with CH2Cl2. The filtrate and washings were combined, washed with 1 N HCl, sat. NaHCO3, H2O and sat. NaCl, dried ( over MgSO4), and evaporated. Purification of the crude product by distillation (bp 110 °C/2.0 mmHg) yielded the corresponding ester, 166 mg (80%), as a colorless oil. The recovered 4 was successively washed with 1 N HCl, H2O, MeOH, and CH2Cl2, and dried at 40 °C.
Esterification of dihydrocinnamic acid with t-butyl alcohol using a recycled 4, after chlorination, under the same conditions described above yielded t-butyl dihydro-cinnamate in 81% yield.

7

Reaction under heating led to the formation of the corresponding polymer-bound guanidine [8] as a side product, which could be estimated in ca. 15% yield by FT-IR.