Resin-Supported Isocyanates

As this area of polymer supported reagents continues to expand the complexity of the polymeric supported resins has increased [18]. Although electrophilic supported reagents like the isocyanate 5 and acid chloride 12 have been shown to be efficient reagents for the covalent capture for primary and secondary amines (Table 1), they are not without their difficulties. The isocyanate resin is particularly expensive and the loading is rather low (approximately 1 mmol NCO/gram). 

Very recently a rapid method for the preparation of effective polymer-supported isocyanate resins has been reported [31]. Gel-type isocyanate resins tvere generated from aminomethyl resins and inexpensive substrates as alternatives to the commercially available, expensive macroporous polystyrene isocyanate supports. Several isocyanates have been investigated phenyl diisocyanate (PDI) tvas found to be the most efficient. Aminomethyl resin was pre-swollen in NMP, mixed with 2 equiv. PDI, and irradiated at 100 °C for 5 min (Scheme 16.7). Filtration, washing with NMP and DCM and drying under vacuum furnished the corresponding isocyanate resin. The reactivity of this novel gel-type resin was better than that of commercially available methyl isocyanate resins and it was successfully used for purification of a small amide library [31]. 

Polyurethane. Very high standards of hygiene are required because the isocyanate resins involved are physiologically active. This should be supported by detailed attention to ventilation and the alertness of the workforce and management... 

The structures of these ylide polymers were determined and confirmed by IR and NMR spectra. These were the first stable sulfonium ylide polymers reported in the literature. They are very important for such industrial uses as ion-exchange resins, polymer supports, peptide synthesis, polymeric reagent, and polyelectrolytes. Also in 1977, Hass and Moreau [60] found that when poly(4-vinylpyridine) was quaternized with bromomalonamide, two polymeric quaternary salts resulted. These polyelectrolyte products were subjected to thermal decyana-tion at 7200°C to give isocyanic acid or its isomer, cyanic acid. The addition of base to the solution of polyelectro-lyte in water gave a yellow polymeric ylide. 

Several other reaction types on solid supports have also been investigated utilizing microwave heating. For instance, in an early report, Yu and coworkers monitored the addition of resin-bound amines to isocyanates employing on-bead FTIR measurements in order to investigate the differences in reaction progress under microwave heating and thermal conditions [63]. 

Liquid-liquid solvent extraction, 21 399 Liquid lithium, 15 131 Liquid low density polyethylene, 20 205 Liquid lubricants, for extreme environments, 15 256 Liquid lubricated system, coefficient of friction in, 15 209 Liquid magnesium, 15 336 Liquid manometers, 20 646-647 Liquid MDI, 25 462. See also MDI [4,4 -methylenebis(phenyl isocyanate)] Liquid melamine resins, 15 773 Liquid membrane extraction, 10 766 Liquid membranes, 15 800, 814-815 supported, 16 28... 

Resin-bound triazenes with a free NH group can be acylated by treatment with acyl halides, or carbamoylated by treatment with isocyanates [342]. The resulting triazene derivatives are stable towards strong bases, but undergo acidolysis when treated with TFA or TMSC1, yielding amides and ureas, respectively (Entries 1 and 2, Table 3.16). Polystyrene-bound triazenes devoid of a free NH group or carbamates can be cleaved from the support by treatment with acyl halides to yield amides (Entries 3 and 4, Table 3.16). 

Support-bound C,F I-acidic compounds, such as acetoacetamides, react with isocyanates under basic conditions to yield amides through C-carbamoylation [71]. Similarly, polystyrene-bound aryllithium compounds can be converted into benzamides by treatment with isocyanates [111]. These reactions are closely related to C-thiocarbamoyla-tion, which has been used for the solid-phase synthesis of thioamides (see Section 13.9). Amides have also been prepared by C-alkylation of resin-bound N-acylaminals with allyltrimethylsilane or diethylzinc (Entry 11, Table 13.7). 

These plates allowed the reaction of resin aliquots with reagents in solution by sealing the filter bottom and to discard the solution and wash the resin by filtering the solutions after removal of the seal. The samples 6.33 were then acylated (step d, monomer set M3, 16 acylating agents, including isocyanates, isothiocyanates, and acid chlorides) to produce 384 resin-bound intermediates 6.34, each as a discrete distributed into 22 different wells. Final cleavage from the support was performed (step e, monomer set... 

Xu and Xong [28] developed a microwave-assisted tracer rapid synthesis of benzimidazoles (xxi) on a polymer support. The arylation of benzylammonia, followed by treatment with N-chlorosulfonyl isocyanate and subsequent hydrolysis gave primary ureas. The Pd-catalysed cyclization of resin bound primary ureas followed by cleavage with TFA-H2O yielded the desired product in good yield and high purities. 

Recently, various scavenger resin approaches have appeared in the literature. For the synthesis of 4000 ureas (400 pools of 10-compound mixtures) [47], a solid-supported amino nucleophile was used to quench the excess of isocyanates, yielding the desired products in good purity. A similar concept has been employed in the synthesis of 2-thioxo-4-dihydropyrimidinones using aminomethylated polystyrene beads to quench isothiocyanates as well as aldehydes [48]. To quench an excess of amine in the synthesis of 2,6,9-trisubstituted purines, formyl polystyrene beads were used to form the corresponding polymer-bound imine, which could be filtered off [49]. 

Preparation of 52 [50] A solution of polymer-supported morpholine 47 (170 mg), l-phenyl-l,3-butanedione 50 (0.5 mmol), and (4-carboxyphenyl)hy-drazine hydrochloride (0.6 mmol) in methanol was shaken for 2.5 h. The methanol was then removed under a stream of nitrogen, dichloromethane (4 mL) and polymer-supported isocyanate 48 (350 mg) were added, and the reaction mixture was shaken for a further 16 h. An additional portion of polymer-supported isocyanate 48 (120 mg) was then added. After 4h, the resin was filtered off and washed with dichloromethane (2 x 1.5 mL). The combined organic phases were concentrated in vacuo to give the desired product, 4-(3-methyl-5-phenylpyrazol-l-yl)benzoic acid 51. 20 mg (70 umol) of this benzoic acid was dissolved in dichloromethane and the solution was treated with polymer-supported morpholine 47 (100 mg) and 0.1 m isobutyl chloroformate in dichloromethane (0.75 mL, 75 pmol). The resulting slurry was shaken under nitrogen at rt for 30 min and then treated with a solution of (3-isopropoxypropyl)amine (100 mg, 85 pmol) in dichloromethane... 

A patent application describes the synthesis of 2,4-quinazolinediones from either immobilized amine reagents or immobilized isocyanates [206]. Utilizing the amine route (Method A in Scheme 36), an Fmoc-protected amino acid immobilized on Sasrin resin [207] was treated with piperidine to provide the free amine derivative. Reaction of a resin-bound amino acid with 2-carboxymethyl phenyl-isocyanate and cyclization of the resulting urea upon treatment with DBU afforded a support-bound 2,4-quinazolinedione. Treatment of the resin with a reactive alkylating agent in the presence of DBU for 10-48 h at 20-70 °C provided the N -alkylated quinazolinedione. The compounds were released from the resin with TFA/CH2CI2. 

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