Carbamate linkers

FIGURE 3.5 Fourier Transform infrared (FTIR) spectra of acrylic rubber (ACM)-siUca hybrid nanocomposites. The numbers after ACM (10 and 50) indicate the wt% tetraethoxysilane (TEOS) concentration. The letters preceding the numbers indicate the ACM-silica samples cross-linked from benzoyl peroxide (B) and a mixed cross-linker hexamethylene diamine carbamate and ammonium benzoate (D). The numbers over the absorption peaks are the wave numbers corresponding to absorbance of those peaks. (From Bandyopadhyay, A., Bhowmick, A.K., and De Sarkar, M., J. Appl. Polym. Sci., 93, 2579, 2004. Courtesy of Wiley InterScience.)... 

Veerman JJN, Rutjes FPJT, Van Maarseveen JH, Hiemstra H. A novel acid stable/base labile carbamate linker for N-acyliminium ion reactions on solid support. Tetrahedron Lett 1999 40 6079-6082. 

Anthranilic acid derivatives of genus D that possess carbamate and urea linkers (W contains an oxygen or nitrogen atom directly linked to the carbonyl carbon, e.g., compounds 18 and 19 respectively) were claimed as GPR109A agonists in a patent application [65]. 

Hong et al. (2004) also found that modification of PAMAM dendrimers with a short PEG linker arm could act to reduce nonspecificity caused by the amines on the dendrimer-modified surface. An azido-PEGj-aininc spacer was activated with nitrophenyl carbamate to yield an activated intermediate that could be used to modify the amines on the dendrimer (Figure 7.24). Reaction at high molar ratio resulted in about 61 PEG-azido spacers on the dendrimer. Reduction of the azido group to an amine using triphenylphosphine in THF provided the dendrimer-PEG-amine derivative for surface modification. The added presence of the PEG spacer arm reduced... 

It is also worthwhile to outline at this place the immobilization procedure that was used for the preparation of type I CSPs A bifunctional linker with a terminal isocyanate on one side and a triethoxysilyl group on the other end (3-isocyanatopropyl triethoxysilane) was reacted with the native cinchona alkaloids quinine and quinidine and subsequently the resultant carbamate derivative in a second step with silica [30], Remaining silanols have been capped with silane reagents, yet, are less detrimental for acidic solutes because of the repulsive nature of such electrostatic interactions. CSPs prepared in such a way lack the hydrophobic basic layer of the thiol-silica-based CSPs mentioned earlier, which may be advantageous for the separation of certain analytes. 

For resin-bound carbamates (18-21), indole linker was the most acid-labile linker for this class of compounds. Rink linker ranked second. Resin (20) was cleaved with 0.5% TFA in 20 min. Resin (21) was cleaved with 1% TFA in 2 min. Resins (18) and (19) required higher concentration of TFA. Resin (18) was cleaved with 1% TFA in 5 h. Alternatively, resin (19) was cleaved with 1% TFA in 12 h and with 5% TFA in only 16 min (not shown). 

For resin-bound ureas (22-25), Indole and Rink linkers, generally ranked 1 and 2 in cleavage kinetics, were still the most acid-labile linker for this class of compounds. Resins (24) and (25) were cleaved with 0.5% TFA in 2 and 23 min, respectively. Resins (22) and (23) were cleaved with 1% TFA in more than 10 h. The order of cleavage rates is similar to carbamate compounds. 

TFA). Among various linkers studied in this work, the indole linker [21] was found to be the most suitable linker in terms of cleavage kinetics and actual cost. Rink linker was the second best in term of kinetics. The rate of cleavage of various functional groups linked to the above-mentioned resins was as follows sul-fonamide>carbamate urea>amide. Results from this study demonstrated that optimization of cleavage conditions often led to more suitable conditions and safer release of precious compounds synthesized on a solid support. 

Spear et al. chose the Heck reaction to elaborate 4-iodophenylsulfonyl chloride attached to Rink amide resin, that is, sulfonamide 18.43 The reaction (Scheme 16) was reported to be quantitative, as was a simple Stille coupling on the same molecule. Raju and Kogan used a Suzuki coupling on solid support (see below)44 to illustrate use of a new carbamate linker for the generation of more diverse sulfonamides than those above. 

Raju and Kogan demonstrated the synthesis of simple, diverse sulfonamides using a new carbamate linker.44 They also showed that the Suzuki reaction could be used for convenient introduction of diversity in their solid-phase synthesis. The three-step sequence is shown in Scheme 48. The purities of the cleaved compounds are good, but the sequence yields are low (32-33%). 

Raju, B. Kogan, T. P. Solid Phase Synthesis of Sulfonamides Using a Carbamate Linker, Tetrahedron Lett. 1997, 38, 3373-3376. 

The development of light-sensitive protective groups began in the early 1960s [129-131] and led to the identification of several functionalities that could be selectively cleaved under UV irradiation (for a review, see [132]). Some of these protective groups, such as 2-nitrobenzyl esters, carbonates, or carbamates [131,133-135], benzoin [136-139], and other phenacyl esters [140] were also found to be useful as photocleavable linkers. 

Benzyl alcohol linkers, such as those described in Section 3.1.1.1, can also be cleaved by palladium-catalyzed hydrogenolysis. Carboxylic acids have, for example, been obtained by hydrogenolysis of insoluble benzyl esters with Pd(OAc)2/DMF/H2 [89,161]. Resin-bound benzylic carbamates [162,163] and amides [164] can also be released by treatment with Pd(OAc)2 in DMF in the presence of a hydrogen source, such as 1,4-cyclohexadiene or ammonium formate. These reactions are quite surprising, because they require the formation of metallic palladium within the gelated beads. 

Allyl esters, carbonates, and carbamates readily undergo C-O bond cleavage upon reaction with palladium(O) to yield allyl palladium(II) complexes. These complexes are electrophilic and can react with nucleophiles to form products of allylic nucleophilic substitution. Linkers based on this reaction have been designed, which are cleavable by treatment with catalytic amounts of palladium complexes [165,166], For the immobilization of carboxylic acids, support-bound allyl alcohols have proven suitable (Figure 3.12, Table 3.7). 

Several different types of linker have been developed that yield amides upon cleavage. These linkers can often also be used to prepare sulfonamides, carbamates, or ureas. There are essentially three different strategies for the release of amides from insoluble supports (a) cleavage of the benzylic C-N bond of resin-bound N-alkyl-N-benzylamides (backbone amide linkers, BAL linkers), (b) nucleophilic cleavage of resin-bound acylating agents with amines, and (c) acylation/debenzylation of resin-bound /V-benzyl-/V,A -dialkylamines. 

Amines can be linked to polymeric alcohols as carbamates. Carbamate attachment of amines can be achieved by reaction of isocyanates with alcohol linkers, or by treatment of alcohol linkers with phosgene [339,427,428] or a synthetic equivalent thereof, followed by exposure to the amine (Figure 3.26). The reagents most commonly used for the activation of alcohol linkers are 4-nitrophenyl chloroformate [69,429-436] and carbonyl diimidazole [427,437-440], The preparation of support-bound carbamates is discussed in Section 14.6. 

The attachment of anilines to benzyl alcohol linkers as carbamates can be achieved either by reaction of aryl isocyanates with a resin-bound alcohol [498-500] or by treat-... 

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