Piperazines, immobilized

In addition to the ionic liquid-mediated procedure in solution (see Scheme 6.112), Leadbeater and coworkers also presented a solid-phase protocol for a one-pot Mannich reaction employing the above mentioned chlorotrityl linker [67]. In this approach, p-chlorobenzaldehyde and phenylacetylene were condensed with readily prepared immobilized piperazines (Scheme 7.56). 

Similarly, a solid-supported imide has been reported to serve as an acylating reagent under microwave conditions by Nicewonger and coworkers [130], The starting imide was immobilized on aminomethyl polystyrene and in this case benzoyl chloride was chosen to prepare the acylating reagent (Scheme 7.111). Primary amines and piperazines were smoothly acylated at room temperature, but more hindered secondary amines required more time and higher temperatures, and anilines... 

To fully use the advantages afforded by multicomponent reaction systems in solid-phase organic synthesis, strategies in which each component is immobilized on the resin must be devised. In this way, individual components can be explored in terms of diversity without the restrictions imposed by immobilization. We have described solid-phase Mannich reactions1 of a resin-bound alkyne (see chapter 5), and we show here that the diversity of products using this chemistry can be enhanced when a different component of the reaction system is immobilized. Specifically, a secondary amine, piperazine, is bound to a resin and then treated with... 

Hydroxymethacrylate-piperazine copolymer with Cl8 ligands and immobilized dextran sulfate... 

Propargyltriphenylphosphine bromide is immobilized on the piperazine to form acid-labile enamines. 

Knoevenagel condensation in a microflow reactor using immobilized piperazine on silica has also been reported. The condensation is carried out in an 800 x 100 pm catalyst channel in borosUicate glass under the EOFconditions (SchemeS.15) [29,30]. Similar work with amine-functionalized silica coatings on microchannel walls has also been reported [31]. 

Nucleophilic substitution reactions of PEG-bound benzylic chloride were easily monitored by NMR spectroscopy. For example, Fig. 3 shows a typical change in chemical shift during the nucleophilic substitution reaction with piperidine. After the coupling reaction was completed, the benzylic protons (8 4.61 ppm, marked as ) of immobilized benzyl chloride 2 completely disappeared and were shifted upfield into the PEG protons absorption area ( 8 3.4-3.8 ppm), but no change was observed in the aromatic region. This evidence showed complete transformation of 2 to a PEG bound amine. Similar results were also obtained by employing other nucleophiles such as piperazine, 4-(aminomethyl)piperidine, and homopiperazine. 

Release of compounds from polymer-bound carbamates has not to be performed via nucleophilic attack but can also be induced by the addition of acids like, for example, TFA in various concentrations. The released target compounds are either primary or secondary amines. The synthesis described in Scheme 34 has been recently published by DoUe et al. [183]. Synthesis of piperazines 227 has been conducted on a or-methylbenzyl resin 223 that has been activated with 4-NPCF and that has been fmther reacted with diethanolamine 224. After mesylation of the two resulting terminal hydroxy groups, reaction with a primary amine 226 and base gave immobilized piper-... 

Amine-catalyzed aldol reaction enhanced by Si02 was reported by Kubota and coworkers in 2003 [8]. In the reaction of 4-nitrobenzaldehyde with acetone catalyzed by piperazine, the addition of mesoporous silica FSM-16 induced the increase in yield of the product from 5% to 91%. Several secondary amines were used as catalysts. In addition, the authors also investigated the amine-immobilized silicas... 

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