Dimethylformamide , solid-phase

Soluble support-based synthetic approaches offer the advantages of both homogeneous solution-phase chemistry (high reactivity, ease of analysis) and solid-phase synthesis (large excess of reagents, simple product isolation and purification) [98,99]. As a representative example, PEG, one of the most widely used soluble polymers, has good solubility in most organic solvents (i.e., dichloromethane, acetonitrile, dimethylformamide, and toluene), but it... 

In a more recent study, Westman and Lundin have described solid-phase syntheses of aminopropenones and aminopropenoates en route to heterocycles [32], Two different three-step methods for the preparation of these heterocycles were developed. The first method involved the formation of the respective ester from N-pro-tected glycine derivatives and Merrifield resin (Scheme 7.12 a), while the second method involved the use of aqueous methylamine solution for functionalization of the solid support (Scheme 7.12 b). The desired heterocycles were obtained by treatment of the generated polymer-bound benzylamine with the requisite acetophenones under similar conditions to those shown in Scheme 7.12 a, utilizing 5 equivalents of N,N-dimethylformamide diethyl acetal (DMFDEA) as reagent. The final... 

The requirements for solid-phase synthesis are diverse. The support must be insoluble, in the form of beads of sufficient size to allow quick removal of solvent by filtration, and stable to agitation and inert to all the chemistry and solvents employed. For continuous-flow systems, the beads also must be noncompressible. Reactions with functional groups on beads imply reaction on the inside of the beads as well as on the surface. Thus, it is imperative that there be easy diffusion of reagents inside the swollen beads and that the reaction sites be accessible. Accessibility is facilitated by a polymer matrix that is not dense and not highly functionalized. A matrix of defined constitution allows for better control of the chemistry. Easier reaction is favored by a spacer that separates the matrix from the reaction sites. Coupling requires an environment of intermediate polarity such as that provided by dichloromethane or dimethylformamide benzene is unsuitable as solvent. 

Piperazine (13) is a base and nucleophile employed (6% in dimethylformamide) in solid-phase synthesis for removal of fluorenylmethyl-based protectors. The reaction is slower (three times) than with piperidine, but it leads to minimal aspartimide or piperazide formation. 

J. B. Ott, J. R. Goates, and D. E. Oyler, Solid Compound Formation from Solutions of N, N-Dimethylformamide with Carbon Tetrachloride and Related Substances. A Solid Phase Transition in N,N-Dimethylformamide , Trans. Faraday Soc., 62, 1511-1518 (1966). 

In 1971, Sheppard proposed that peptide synthesis would proceed more efficiently if the polymeric support was designed to have solvation properties similar to those of the peptide product.This line of reasoning led to the development of polyamide resins.The most successful of this type of support is based on cross-linked poly(dimethylacrylamide) (Pep-syn). Polyamide resins swell up to 10 times their dry volume in dimethylformamide and even more in water. On the other hand, they swell much less in dichloromethane. The few comparative studies that have been carried out between polystyrene and polyamide resins indicate that both give very similar results in routine solid-phase peptide synthesis. 

A nonpolar solvent favors conformation A, whereas conformation B is favored by more polar solvents (e.g. dimethylformamide, hexamethylphosphoric triamide) because the cation is more solvated (cf. Table 9, entries 1 and 2). However, this solvent effect is absent when BujP Cu" is used as counterion. Conformation A is more favored by relatively small counterions, such as the lithium and sodium ion, as compared to the larger potassium ion, due to the higher degree of association of the former. Steric strain between ASG and ASG is minimized in conformation B. Conformations A and B lead to trans- and c -substituted cyclopropanes, respectively. A study of cyclopropane esters, -in which the stereoselectivity of the reaction of polymer-supported reagents was compared with molecules of low-molecular weight, made clear that the steric and polar microenvironment of the polymer-supported reaction is not different enough in bulk to influence the selectivity substantially. Nevertheless, a specific influence of the solid phase can be observed at low temperatures. 

In order to follow the mutarotation, the sample (5 tL) is quickly dissolved in 2V,A(-dimethylformamide and the solution is cooled in liquid nitrogen. The sily-lating mixture is added, allowed to warm to room temperature, then applied to a column. Used at 15()-200 C, the column contains a liquid with a high boiling point, adsorbed on a powdery solid phase. Utilizing this method, it is possible to observe as many peaks on the chromatogram as there are tautomers in noticeable quantities in solution. Identifying the peaks requires the isolation of fractions in a measurable quantity. 

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