Three-phase tests

A polymer-bound phenanthroline has also played an integral role in the development and establishment of the so-called three-phase test for detection of short-lived reaction intermediates (75JA3453). The amount of reactant available on the surface of a spherically-shaped, crosslinked polymeric reagent is, in general, very small, and it is imperative in order to achieve substantial conversion that reaction occurs within the interior of the... 

A variant of the trapping experiment, which physically excludes the possibility of the direct reaction of the trap with reactant, is found in the three-phase test [24]. This exploits the availability of an increasing range of polymeric solid supports (PS in Fig. 9.7) to which reactants and trap maybe separately attached. The direct reaction between the solid-supported trap and solid-supported reactant is not anticipated, but control experiments to establish this are advisable. The formation of the trapping product (Q) when the polymer-supported reactant and polymer-supported trap are dispersed together in a solution under conditions where the suspected intermediate would be released from the reactant is then clear evidence... 

Scheme 9.10 Application of a three-phase test to investigate the nature of the catalyst in a heterogeneous Heck reaction.

The free existence in solution of l-azetin-4-one has been demonstrated for the first time by using the three-phase test (90JOC434). The intermediate was generated from a 4-polymeric sulfonate 2-azetidinone, which is able to act as its nonpolymeric analogue 4-acetoxy-2-azetidinone in reactions with nucleophilic compounds. 

The three-phase test has been used to distinguish between associative and dissociative mechanisms. Thus, in this case the negative results in the trapping of the intermediate with dienic polymers seem to support a stepwise mechanism in the formation of cyclocondensation adducts with siloxydienes and l-azetin-4-one. 

Aza-2,4-cyclopentadienone and 3-aza-2,4-cyclopentadienone are two reactive intermediates (75AG38) whose existence has been demonstrated by using the three-phase test. The precursor polymers for both compounds have been prepared (36) from maleimide, which was reduced with LiAlH4 and linked to the sulfonic polymer, and (39) by reaction between (37) and (38) (88JA4017 91JOC5417). 

The existence and reactivity of the parent compounds, 2,5-diaza-2,4-cyclopentadienone (94) and 3,4-diaza-2,4-cyclopentadienone (95), have also been demonstrated by using the three-phase test. Its reactivity as dienes and as dienophiles has been tested against several... 

Kautsky s three-phase test indicated that the excited yellow dye generated diffusible excited 02 species that were able to reach the colourless gel particles and to oxidize the leuco dye. In spite of this convincing evidence, his hypothesis was strongly challenged and... 

A very clever three-phase test for the detection of metaphosphate intermediates in phosphoryl transfer reactions has been described by Rebek and coworkers (44). The basis of this test is the use of two polymers suspended in solution. The donor polymer contains a potential precursor to metaphosphate anion, e.g., an acyl phosphate or a phosphoramidate, and the recipient polymer contains an acceptor nucleophile, e.g., an amine. After reaction and physical separation of the polymers, the recipient polymer is analyzed for covalently bound phosphate. Since very few of the phosphoryl groups to be transferred will be on the surface of the donor polymer, detection of significant transfer to the recipient polymer provides evidence for a diffusible intermediate, i.e., free metaphosphate anion. Significant transfer did occur in dioxane or acetonitrile suspensions of the polymers, thereby providing evidence for an intermediate. However, this test for diffusible and, therefore, relatively stable metaphosphate anion is compromised by the choice of solvent. Both dioxane and acetonitrile can provide unshared electron pairs for the highly electrophilic metaphosphate anion such that the actual species that migrates from the donor polymer to the recipient polymer may be a complex between metaphosphate anion and the solvent. Such a role for solvent has been investigated stereochemically, the results of which will be described later in this section. 

The laboratories of both Knowles and Cullis have described solvolysis conditions in which free metaphosphate anion can exist. Initially both laboratories investigated the possible stabilization of metaphosphate anion by acetonitrile, since this solvent was reported by Rebek et al. to allow a successful application of the three-phase text for free metaphosphate anion (44). The Harvard laboratory studied the reaction of phenyl (, 0, 0]phosphate with rert-butanol in acetonitrile (56), and the Leicester laboratory studied the reaction of [)8- 0, 0, 0]ADP with 2-0-benzyl-(5)-1,2-propanediol in acetonitrile (57). In both cases, complete racemization was observed, and this can be explained by the complexation of metaphosphate anion by the acetonitrile solvent. Thus, the success of the three-phase test of Rebek et al. for metaphosphate presumably can be attributed to diffusion of an acetonitrile-metaphosphate anion complex rather than free metaphosphate anion. 

The diaryliodonium carboxylate route to benzynes (Type B2) has been adapted to the polymer-bound precursor 58, prepared from Merrifield s resin by standard methods". (An earlier example of a polymer-bound h nzyne has been described. ) The polymer afforded benzyne 59 when heated above 200 °C, as demonstrated by trapping with 2-furoic acid the initial cycloadduct decarboxylates spontaneously at that temperature, affording naphthols 60 in about 20% yield. The three-phase test involving transfer of aryne from 58 to a... 

Scheme 12.3 Steps of the three-phase test. First it is required to attach covalently a reactive group (RC) to a solid surface. Then the reaction with a substrate and RC is carried out in solution in the presence of the solid with RG and the catalyst. If leaching occurs, in addition to observing the product in solution, the RG should be transformed into the corresponding product.

Further proof that cyclobutadiene liberated by ceric oxidation of the iron carbonyl complex is completely free of the metal comes from an ingenious new three-phase test for reactive intermediates which resembles the Paneth test for free radicals in its basic flow design. Thus, a cyclobutadiene-iron carbonyl complex bound to a support of polymer beads is treated as a suspension with Ce in the presence of separate polymer beads to which a trapping agent (maleimide) is bound. The resulting adduct is then liberated from the second polymer by hydrolysis for identification, its isolation... 

To address these limitations, additional -tests have been designed. In one experiment called the "three-phase test," a substrate is attached to an insoluble support, such as a polymer. If the catalyst is also a solid, then the supported substrate reacts much more slowly than the analogous soluble substrate, but if the catalyst is dissolved, then the two substrates will react with more similar rates. The polymer-bonded substrate must be swollen in a solvent which is compatible with the homogeneous catalyst. Applications of this test for homogeneity are Illustrated in Equation 10.54. The virtue of this test is that it is based on the catalytic process itself, rather than on detection of hypothetical catalysts. A variation of this theme involves the use of polymeric catalyst poisons, such as polythiols. These were found to have no effect on heterogeneous catalysts but to retard homogeneous catalysts.- ... 

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