Isocyanates polymer supports

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. 

The second general method, IMPR, for the preparation of polymer supported metal catalysts is much less popular. In spite of this, microencapsulation of palladium in a polyurea matrix, generated by interfacial polymerization of isocyanate oligomers in the presence of palladium acetate [128], proved to be very effective in the production of the EnCat catalysts (Scheme 3). In this case, the formation of the polymer matrix implies only hydrolysis-condensation processes, and is therefore much more compatible with the presence of a transition metal compound. That is why palladium(II) survives the microencapsulation reaction... 

Alkyl and glycosyl isocyanates and isothiocyanates are produced in good yield under phase-transfer catalytic conditions using either conventional soluble catalysts or polymer-supported catalysts [32, 33]. Acyl isothiocyanates are obtained under similar conditions [34]. A-Aryl phosphoramidates are converted via their reaction with carbon disulphide under basic conditions into the corresponding aryl isothiocyanates, when the reaction is catalysed by tetra-n-butylammonium bromide [35]. 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

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],... 

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). 

A robust catch, cyclize, and release preparation of 3-thioalkyl-1,2,4-triazoles mediated by the polymer-bound base P-BEMP has been described <02TL5305>. Reaction of solid-supported hydrazides 103 with isocyanates or isothiocyanates followed by base-induced cyclization/cleavage afforded 1,2,4-trisubstituted urazoles and thiourazoles 104 <02JCO491, 02TL3899>. Polymer-supported V-acyl-1 //-benzotriazole- 1-carboximidamides 105 reacted with hydrazines followed by acidic cyclizative release to give 3-alkylamino-l,2,4-triazoles 106 <02OL1751>. 

Polymers with pendant carbodiimide groups 27 are also synthesized from crossUnked polystyrene. In this synthetic route crossUnked polystyrene beads are chloromethylated and converted to the amines. Reaction with isopropyl isocyanate gives the corresponding ureas, which are treated with tosyl chloride and triethylamine to produce the crossUnked polycarbodiimides. This polymer is used in the polymer supported Moffatt oxidation of alcohols into aldehydes or ketones using benzene/DMSO. ... 

The triethoxysilane endgroup had to be introduced as the respective isocyanate and was then used to attach the polymer on the silicon support. In a final step, the NHC are formed and the ruthenium precursor loaded onto the polymer. Only 13% of the imidazolium sites are attached to ruthenium. The formation of this polymer supported Grubbs catalyst is doubtless a synthetic masterpiece, however, immobilisation of the Grubbs catalyst was achieved in a far less complicated manner only a few years later by a far simpler method by Fiirstner and coworkers [244]. 

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. 

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... 

Preparation of the reagent [70] A solution of PEG monomethyl ether 89 (MW = 750 5.88 g, 7.8 mmol) in benzene (20 mL) was dried azeotropically for 24 h in an apparatus fitted with a Dean-Stark trap and subsequently added dropwise to a solution of chlorosulfonyl isocyanate (88) (1.10 g, 7.8 mmol) in dry benzene (20 mL). The mixture was stirred at room temperature for 1 h, then concentrated to dryness. A solution of this residue in benzene (35 mL) was added dropwise to a solution of triethylamine (2.5 mL, 17.3 mmol) in benzene (15 mL). The mixture was stirred for 30 min at room temperature, then filtered, and the solid was dried to yield polymer-supported Burgess reagent 91 (6.2 g, 82%). 

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]. 

---