Solid suspension synthesis

Solid-phase synthesis of 3,4-disubstituted (3-lactams was accomplished [104] via reaction of in situ generated ketenes with immobilized aldimines under mild conditions. Initially Fmoc-protected Wang resin strategy was followed (Scheme 15) and the [2+2] cycloaddition was performed by adding phenox-ylacetyl chloride (49, R1 = phenoxy) and triethylamine in excess to a suspension of 48 in dichloromethane. The yields ranged from good to very good for the five-step synthetic sequence and exclusive formation of the cis isomer was detected in all cases. 

Incorporation of the F-Tag Cap into the Automated Solid-Phase Synthesis Cycle. The resin (50 /imol) was swelled in a 0.1 M solution of 2,6-lutidine in CH2C12 (4 ml, 8.0 equiv.). After vortexing for 5 s, a 0.1 M solution of the F-Tag triflate in CH2C12 (2.5 ml, 5.0 equiv., loaded into cartridges) was delivered to the reaction vessel. Mixing of the suspension was performed (10 s vortex, 50 s rest) for 15 min. 

Investigating the kinetically controlled synthesis of the /flactam antibiotic amoxicillin from 6-aminopenicillanic acid and D-p-hydroxyphenylglycine methyl ester in a solid suspension system in which the reaction nevertheless occurred in the liquid phase, Diender et al. found that the pH value and dissolved concentrations took a very different course at different initial substrate amounts (Diender, 2000). These results were described reasonably well by the model based on mass and charge balances, pH-dependent solubilities of the reactants, and enzyme kinetics. 

In the design of upflow, three phase bubble column reactors, it is important that the catalyst remains well distributed throughout the bed, or reactor space time yields will suffer. The solid concentration profiles of 2.5, 50 and 100 ym silica and iron oxide particles in water and organic solutions were measured in a 12.7 cm ID bubble column to determine what conditions gave satisfactory solids suspension. These results were compared against the theoretical mean solid settling velocity and the sedimentation diffusion models. Discrepancies between the data and models are discussed. The implications for the design of the reactors for the slurry phase Fischer-Tropsch synthesis are reviewed. 

Fast Chemical Reactions in Liquid-solid Systems (Condensation Method of Suspension Synthesis)... 

Via Resin-Bound Benzenesulfinate Linker. The use of resin-bound benzenesulfinate in solid-phase synthesis was first reported in 1989 by Huang and coworkers for the synthesis of substituted acrylates (Scheme 12.2). The synthesis was performed using resin-bound sodium benzenesulfinate, which was prepared by bubbling sulfur dioxide into a suspension of cross-linked polystyrene, AICI3/HCI, and carbon disulfide to obtain the resin-bound benzenesulfinic acid that in turn was treated with sodiumhydroxide to yield the resin-bound sodium benzenesulfinate (Scheme 12.2). 

Synthetic organic polymers, which are used as polymeric supports for chromatography, as catalysts, as solid-phase supports for peptide and oligonucleotide synthesis, and for diagnosis, are based mainly on polystyrene, polystyrene-divinylbenzene, polyacrylamide, polymethacrylates, and polyvinyl alcohols. A conventional suspension of polymerization is usually used to produce these organic polymeric supports, especially in large-scale industrial production. 

When the polymer was prepared by the suspension polymerization technique, the product was crosslinked beads of unusually uniform size (see Fig. 16 for SEM picture of the beads) with hydrophobic surface characteristics. This shows that cardanyl acrylate/methacry-late can be used as comonomers-cum-cross-linking agents in vinyl polymerizations. This further gives rise to more opportunities to prepare polymer supports for synthesis particularly for experiments in solid-state peptide synthesis. Polymer supports based on activated acrylates have recently been reported to be useful in supported organic reactions, metal ion separation, etc. [198,199]. Copolymers are expected to give better performance and, hence, coplymers of CA and CM A with methyl methacrylate (MMA), styrene (St), and acrylonitrile (AN) were prepared and characterized [196,197]. 

Microwave irradiation has been used to accelerate the Gewald reaction for the one-pot synthesis of N-acyl aminothiophenes on solid support [67]. A suspension of cyanoacetic acid Wang resin 35, elemental sulfur, DBU and an aldehyde or ketone 36 in toluene was irradiated for 20 min at 120 °C in a single-mode microwave synthesizer (Scheme 13). Acyl chloride 37 was added, followed by DIPEA, and the mixture was irradiated for 10 min at 100 °C. After cooling to room temperature, the washed resin was treated with a TEA solution to give M-acylated thiophenes 38 in 81-99% yield and purities ranging from 46-99%. 

Toxi-ChromoPad (EBPI, Ontario, Canada) is a simple method for evaluation of the toxicity of solid particles [25,26,32,39]. The test is based on the inhibition of the synthesis of (3-galactosidase in E. coli after exposure to pollutants. The method has been used to measure acute toxicity of sediment and soil and other solid samples. The test bacterial suspension is mixed with homogenized samples and incubated for 2 hours. A drop of the test solution is pipetted onto a fiberglass filter containing an adsorbed substrate. A color reaction indicates the synthesis of enzyme, while a colorless reaction indicates toxicity. It has previously been shown... 

The industrial synthesis of polyformaldehyde [poly(oxymethylene)] occurs by anionic polymerization of formaldehyde in suspension. For this the purification and handling of monomeric formaldehyde is of special importance since it tends to form solid paraformaldehyde. After the polymerization the semiacetal end groups have to be protected in order to avoid thermal depolymerization (Example 5-13). This is achieved by esterfication with acetic anhydride (see Example 5-7). As in the case of trioxane copolymers (see Sect. 3.2.3.2) the homopolymers of formaldehyde find application as engineering plastics. 

---