Isocyanates, scavenging

Furthermore, reductive amination of fiiranose aldehydes 63 with secondary amines 68 yielded tertiary amines 69. Here, after removal of borates with Amberlite lRA-743, polymer-supported isocyanate scavenged out excess amine. The resulting acetonides 69 were treated with alcohols 70 in the presence of acid to yield mixed acetals 71. A final treatment with polymer-supported piperidine removed trace amounts of acid and ensured long-term stability of acetals 71. These library syntheses highlighted the use of functionalized scavenger resins to purify intermediates and products. 

Figure 5 illustrates the type of encapsulation process shown in Figure 4a when the core material is a water-immiscible Hquid. Reactant X, a multihmctional acid chloride, isocyanate, or combination of these reactants, is dissolved in the core material. The resulting mixture is emulsified in an aqueous phase that contains an emulsifier such as partially hydroly2ed poly(vinyl alcohol) or a lignosulfonate. Reactant Y, a multihmctional amine or combination of amines such as ethylenediamine, hexamethylenediamine, or triethylenetetramine, is added to the aqueous phase thereby initiating interfacial polymerisation and formation of a capsule shell. If reactant X is an acid chloride, base is added to the aqueous phase in order to act as an acid scavenger. 

Scavenging acid chlorides, sulfonyl chlorides, isocyanates, and other electrophiles... 

Reductive amination of an aldehyde with excess primary amine, using a support-bound borohy-dride, provides the desired secondary amine contaminated with the primary amine precursor. Covalent capture of the primary amine with a support-bound aldehyde provides the pure secondary amine. Treatment with excess isocyanate yields the final urea product, which is purified by reaction with a support-bound amine to remove unreacted isocyanate. For the full potential of this method to be realized, further development of support-bound reagents and scavengers for most of the important chemical transformations will be necessary. Al-... 

Kaldor [49 i, 55] demonstrated the advantages of applying solid-supported scavengers to the preparation of parallel arrays in a multi-step fashion. In these studies he examined the clean-up of multiple amine alkylation and acylation reactions using a variety of immobilized electrophilic and nucleophilic scavenger reagents including an amine, isocyanate, aldehyde and acid chloride (Tab. 2.1). 

Williams and coworkers used a [G4]-PAMAM dendrimer as a scavenger in the reactions of an arylpiperazine with slight excesses of three different electrophiles (an isocyanate, a sulfonyl chloride, and a benzyl halide) [62]. After TLC had indicated that all amine substrate had reacted the dendritic scavenger was added. Solvent removal, adding of chloroform, and filtration of the unsoluble dendrimer afforded the products in high yields (87-99%) and purities (>95%, HPLC). 

In an opposite manner to bases such as 1 and 2 in terms of reactivity, polymer-supported tosyl chloride equivalent 14 is able to capture alcohols as polymer-bound sulfonates 15, which are released as secondary amines, sulfides and alkylated imidazoles with primary amines, thiols and imidazoles as nucleophiles in a substitution process (Scheme 6) [24]. This technique has further been extended for the preparation of tertiary amines [25] and esters [26]. Excess of amine was scavenged by polymer-supported isocyanate 16 [27, 28] while excess of carboxylic acid was removed by treatment with aminomethylated polystyrene 17. 

Two complementary procedures have been developed for alkylation of secondary amines [11] - both of which involve the use an excess of amine to drive the reaction to completion. The remaining amine was removed from the required tertiary amine using a polymer supported isocyanate 5 as a nucleophilic scavenger (under thermodynamic control) (Table 1 entry 2). The use of this amine scavenger has subsequently been applied in the purification of urea-based libraries prepared by solid-phase organic synthesis [12],... 

Scavenger resins and polymer-bound reagents are routinely used to prepare medium-sized (500-1000 member) libraries. Polymer-bound isocyanates (9) and aldehydes (10) are used to remove amines from reaction mixtures, while polymer-bound thiols (11) are used to scavenge halides. 

Isocyanates also can react with each other to produce carbodiimides with the loss of carbon dioxide. This reaction requires high temperatures unless catalyzed by specific phosphorus compounds. Formation of carbodiimides normally is not an important cross-linking mechanism in polyurethane adhesives. However, carbodiimides are sold by Dow Chemicals (Ucarlnk ), Nisshinbo Industries (Carbodilite ), and Stahl USA (XR-2569). They have been recommended as water scavengers, crosslinkers, and stabilizers for carboxyl functional polyurethanes. The carbodiimide can react with water to give a urea, which still can react with additional isocyanate to produce a biuret. 

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