Imides polymer-supported

Scheme 7.111 Recyclable polymer-supported imides for amide synthesis.

Initial investigations of base-catalyzed imidization of polymeric systems, in particular PMDA/ODA based polyfamic alkyl esters), have been difficult due to the insolubility of the polyimide precursor at imidization levels exceeding 40%. Nevertheless, preliminary studies indicate that the base-catalyzed polymer imidization reaction appears to be significantly slower at ambient temperatures as compared to the phthalamide model compounds. It is yet unclear whether this is a direct result of the conformational aspects associated with the polymer chain or solubility considerations arising from the less soluble, partially imidized polymer chain. Since much of the initial work involved IR studies of supported... 

Y. Y. Chu, Y. Synthetic studies on d-biotin, part 6 an expeditious and enantiocontrolled approach to the total synthesis of d-biotin via a polymer-supported chiral oxazaborolidine-cata-lyzed reduction of meso-cyclic imide strategy. Synthesis 2003, 2155-2160. 

An acylated disaccharide 75 was efficiently prepared using polymer-supported reagents. Formation of glycosyl imidate 72 was carried out with Dowex 1-8X (OH form) as a polymer-supported base, and glycosylation of acceptor 73 with the imidate 72 was carried out using... 

RCO2H, R OH, DCC/DMAP, EtjO, 25°C, l-24h, 70-95% yield. This method is suitable for a large variety of hindered and unhindered acids and alcohols. The use of Sc(OTf)3 as a cocatalyst improves the esterification of 3° alcohols. Carboxylic acids that can form ketenes with DCC react preferentially with aliphatic alcohols in the presence of phenols whereas those that do not show the opposite selectivity. In some sterically congested situations the 0-acyl urea will migrate to an unreactive A-acyl urea in competition with esterification. Carbodi-imide I was developed to make the urea by-product water soluble and thus easily washed out. Isoureas are prepared from a carbodiimide and an alcohol which upon reaction with a carboxylic acid give esters in excellent yield. A polymer supported version of this process has been developed. This process has been reviewed. Note that DCC is a potent skin irritant in some individuals. 

Cyclization to the desired head-to-taU-linked bis-benzimidazoles can also be performed by reaction of aryl or alkyl isothiocyanates with N,N -dicyclohexylcarbodi-imide (DCC) [83]. In a closely related and more recent study by the same group, mercury chloride was used as a catalyst to perform cyclization to the benzimidazoles [84]. Another application of the bis-hydroxylated polymer support PEG 6000, microwave-accelerated liquid-phase synthesis of thiohydantoins, has been reported [85, 86]. 

Scheme 16.82. A polymer-supported imide-based acylating agent.

Reggelin and Brenig reported a different approach for the asymmetric synthesis on solid support (Scheme 1.6.38). An acylated Evans auxiliary was used as a soluble reagent for the transformation of polymer-supported aldehyde 81 into imide 82. The latter was converted into the Weinreb amide 83 which was - after protection of the hydroxyl group - submitted to DIBAH reduction to generate aldehyde 84. 

Ketones [60], P-fimetionalized ketones [61] [62] and meso eylic imide [63] have been enantioselectively redueed using polymer-supported chiral sulfonamides in presence of boranes (NaBH4/Me3SiCl or BH3.SMe2), leading in situ to the eorresponding oxazaborolidine polymer-supported chiral sulphonamide 70 (Scheme 32). 

Me5o-cyclic imide precursor of t/-biotin has successfully been reduced with BHs.SMe2 in the presence of polymer-supported sulphonamide catalyst 70 in THF imder reflux for 6 hours. (Scheme 33) [63]. The enantioselective hydroxylactam was obtained in 91% yield with an ee > 98.5%. The recycling of the chiral supported-sulfonamide in the reduction of the meso precursor of J-biotin could be involved at least 5 times with non change in activity and enantioselectivity. 

The polymeric imide could then be reacted with primary amines or ammonia to form ammonium salts for a subsequent reactions with a carboxylic acid in the presence of a coupling reagent. It could then be converted to amides or functionalized as a uranium salt for use as polymer-supported peptide coupling. In addition, the anhydride was also reacted with di(2-pyrldyl)methylamine and formed a recoverable palladium catalyst for cross-coupling reactions that could take place in water. 

This work was supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNCS-UEFISCDI, project PN-ll-RU-TE-2014-4-2976, no. 256/1.10.2015. Special thanks are addressed to Dr. Silvia loan and Dr. Camelia Hulubei from Petru Poni Institute of Macromolecular Chemistry-Romania for supervising the rheological experiments of liquid crystal polymer solutions and for synthesis of some imidic polymers containing aliphatic units, respectively. 

Several examples have shown that the degree of activity resulting from synthesis is reproducible, as is the amino acid composition. In other cases, e.g., with p-nitrophenyl acetate, activity was quite variable. Nearly total inactivation by heat in aqueous solution has been demonstrated for some pyropolyamino acids other such systems are heat-stable in aqueous solution. In the p-nitrophenyl acetate system, the nature of the heat inactivation, if not the mechanistic reason for enhanced activity, is understood to involve both imide and imidazole residues. Differing interactions of these residues to produce loci of varying degrees of efficiency could help to explain the quantitative nonreproducibility of activity in separate syntheses. With OAA, selectivity of action was strict, in that several a-keto acids were not measurably acted upon under controlled conditions. The identification of the active locus for hydrolysis of the substrate p-nitrophenyl acetate supports the general inference of specificities, inasmuch as similarly prepared polymers have been shown not to be operative for other reactions, e.g., decarboxylation of OAA (17). 

The FTIR spectra of the polymers exhibited two characteristic absorption bands at 1785 and 1730 cm"l due to the stretching modes of the imide rings. The absorption peaks of the nitro group occurred at 1518 and 1340 cm. These results support the imide structure and indicate the existence of the NLO chromophore. 

White [25] investigated the transport properties of a series of asymmetric poly-imide OSN membranes with normal and branched alkanes, and aromatic compounds. His experimental results were consistent with the solution-diffusion model presented in [35]. Since polyimides are reported to swell by less than 15%, and usually considerably less, in common solvents this simple solution-diffusion model is appropriate. However, the solution-diffusion model assumes a discontinuity in pressure profile at the downstream side of the separating layer. When the separating layer is not a rubbery polymer coated onto a support material, but is a dense top layer formed by phase inversion, as in the polyi-mide membranes reported by White, it is not clear where this discontinuity is located, or whether it wiU actually exist The fact that the model is based on an abstract representation of the membrane that may not correspond well to the physical reality should be borne in mind when using either modelling approach. 

---