Amine immobilizations

Chiral crown ethers based on IB-crown-6 I Fig. 4> can form inclusion complexes with ammonium ions and proionated primary amines. Immobilization of these chiral crown ethers on a chromatographic support provides a chiral stationary phase which can resolve most primary amino acids, amines and amino alcohols. However, the stereogenic center must be in fairly close proximity in the primary aininc lor successful chiral separalion. Significantly, ihe chiral crown ether phase is unique in that ii is one of the few liquid chromatographic chiral stationary phases that does not require the presence of an aromatic ring to achieve chiral separations. 

Tsuchia, E., Nishide, H. Selective adsorption of metal ions to polymeric amines immobilized by template reaction, in Polymeric amines and ammonium salts (ed.) Goethals, E. J., p. 271, New York. Pergamon Press 1980... 

Ramamurthy and coworkers reported the photochemical electron-transfer-initiated intermolecular hydrogen transfer reaction [80,81] of phenyl cyclohexyl ketone 25 in chiral amine-immobilized zeolk cavities. 

Secondary amines, immobilized on mesoporous FSM-16 silica by the same methodology, were utilized to obtain substituted 5-ketoaldehydes, which are important synthons for the preparation of natural products such as terpenoids, by direct 1,4-conjugate addition of unmodified aldehydes to vinyl ketones (Scheme 3.15). ... 

Primary amines immobilized in the acidic montmorillonite (H+-mont) interlayer space, prepared by a silane-coupling reaction using 3-aminopropyltriethoxysilane, acted as base sites together with the interlayer acid sites to promote tandem deacetalization-Knoevenagel condensation (Scheme 6.22) [134]. On the basis of CP/MAS (CP, cross-polarization) NMR results, it is proposed that a free NH2 group in an expanded interlayer space of H+-mont in the presence of heptane... 

The amine-immobilized silica-alumina catalyst achieved a good yield of 2-cyano-5-oxo-2-(3-oxobutyl) hexanoic acid ethyl ester from the Michael reaction between nitrile and a,P-unsaturated ketone (Table 7.6). Notably, the reaction using a mixture of triethylamine and unfunctionahzed sihca-alumina gave a lower yield than the amine-immobilized silica-alumina, and both triethylamine and silica-alumina were inactive alone for the reaction. In general, the conjugate addition of nitrile compounds to a,P-unsaturated ketones requires strong base or transition metal... 

Solid-supported chemistry, primary or secondary amine immobilized, yields 21-75%... 

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... 

Scheme 1.8 Mechanism for tertiary amine immobilization on the SA surface.

To more precisely control the acid-base interaction of the silica-alumina-supported tertiary amine catalyst for organic synthesis, we examined the control of the density of surface Si-OH groups [15]. According to the above-mentioned immobilization mechanism, if the Si-OH density decreases, the acid-base interaction should be decease because of the far amine-immobilization positions from strong acid sites, resulting in lower acid-base interaction and higher catalytic performance. 

Heterogeneous hydrogenation catalysts can be used in either a supported or an unsupported form. The most common supports are based on alurnina, carbon, and siUca. Supports are usually used with the more expensive metals and serve several purposes. Most importandy, they increase the efficiency of the catalyst based on the weight of metal used and they aid in the recovery of the catalyst, both of which help to keep costs low. When supported catalysts are employed, they can be used as a fixed bed or as a slurry (Uquid phase) or a fluidized bed (vapor phase). In a fixed-bed process, the amine or amine solution flows over the immobile catalyst. This eliminates the need for an elaborate catalyst recovery system and minimizes catalyst loss. When a slurry or fluidized bed is used, the catalyst must be separated from the amine by gravity (settling), filtration, or other means. 

Other immobilization methods are based on chemical and physical binding to soHd supports, eg, polysaccharides, polymers, glass, and other chemically and physically stable materials, which are usually modified with functional groups such as amine, carboxy, epoxy, phenyl, or alkane to enable covalent coupling to amino acid side chains on the enzyme surface. These supports may be macroporous, with pore diameters in the range 30—300 nm, to facihtate accommodation of enzyme within a support particle. Ionic and nonionic adsorption to macroporous supports is a gentle, simple, and often efficient method. Use of powdered enzyme, or enzyme precipitated on inert supports, may be adequate for use in nonaqueous media. Entrapment in polysaccharide/polymer gels is used for both cells and isolated enzymes. 

In recent years the solid-phase hydrosilylation reaction was successfully employed for synthesis of hydrolytically stable surface chemical compounds with Si-C bonds. Of special interest is application of this method for attachment of functional olefins, in particular of acrolein and some chiral ligands. Such matrices can be used for subsequent immobilization of a wide range of amine-containing organic reagents and in chiral chromatography. 

Ion exchange, in which cation and/or anion resins are used to replace undesirable anionic species in liquid solutions with nonhazardous ions. For example, cation-exchange resins may contain nonhazardous, mobile, positive ions (e g., sodium, hydrogen) which are attached to immobile acid groups (e.g., sulfonic or carboxylic). Similarly, anion-exchange resins may include nonhazardous, mobile, negative ions (e.g., hydroxyl or chloride) attached to immobile basic ions (e.g., amine). These resins can be used to eliminate various species from wastewater, such as dissolved metals, sulfides, cyanides, amines, phenols, and halides. 

This amide, readily formed from an amine and the anhydride or enzymatically using penicillin amidase, is readily cleaved by penicillin acylase (pH 8.1, A -methylpyrrolidone, 65-95% yield). This deprotection procedure works on peptides, phosphorylated peptides, and oligonucleotides, as well as on nonpeptide substrates. The deprotection of racemic phenylacetamides with penicillin acylase can result in enantiomer enrichment of the cleaved amine and the remaining amide. An immobilized form of penicillin G acylase has been developed. ... 

The Zincke reaction has also been adapted for the solid phase. Dupas et al. prepared NADH-model precursors 58, immobilized on silica, by reaction of bound amino functions 57 with Zincke salt 8 (Scheme 8.4.19) for subsequent reduction to the 1,4-dihydropyridines with sodium dithionite. Earlier, Ise and co-workers utilized the Zincke reaction to prepare catalytic polyelectrolytes, starting from poly(4-vinylpyridine). Formation of Zincke salts at pyridine positions within the polymer was achieved by reaction with 2,4-dinitrochlorobenzene, and these sites were then functionalized with various amines. The resulting polymers showed catalytic activity in ester hydrolysis. ... 

An example for this approach is the immobilization of (5 )-(-)-a-A-(2-naph-thyl)leucine, a 7t-donating group on silica. This chiral selector exhibits excellent recognition for 3,5-dinitrobenzoyl (DNB)- and 3,5-dintroanilido (DNAn)-deriva-tives. Amines and alcohols can be derivatized with DNB- or DNAn-chloride to the esters or carbamates and separated on the CSP, as shown by Pirkle for a wide variety of compounds [27]. 

The microwave acceleration of Ugi condensations on a sohd support have been utilized in the synthesis of an 18-membered targeted hbrary of a-acylamino amides [60], Irradiation of the four components, immobilizing the amine on TentaGel S RAM, for 3-5 min in a single-mode microwave synthesizer gave the products in moderate to excellent yields and high purity (Scheme 7). 

Jacobs et al. have found that the efficiency of the Pd-catalyzed racemization of amines can be improved by using Pd immobilized on supports such as BaS04, CaC03, or BaC03. The racemization was combined with a KR catalyzed by CALB affording enantiopure acetylated benzylamines in high yields [37]. 

The resolution of racemic ethyl 2-chloropropionate with aliphatic and aromatic amines using Candida cylindracea lipase (CCL) [28] was one of the first examples that showed the possibilities of this kind of processes for the resolution of racemic esters or the preparation of chiral amides in benign conditions. Normally, in these enzymatic aminolysis reactions the enzyme is selective toward the (S)-isomer of the ester. Recently, the resolution ofthis ester has been carried out through a dynamic kinetic resolution (DKR) via aminolysis catalyzed by encapsulated CCL in the presence of triphenylphosphonium chloride immobilized on Merrifield resin (Scheme 7.13). This process has allowed the preparation of (S)-amides with high isolated yields and good enantiomeric excesses [29]. 

The second step introduces the side chain group by nucleophilic displacement of the bromide (as a resin-bound a-bromoacetamide) with an excess of primary amine. Because there is such diversity in reactivity among candidate amine submonomers, high concentrations of the amine are typically used ( l-2 M) in a polar aprotic solvent (e.g. DMSO, NMP or DMF). This 8 2 reaction is really a mono-alkylation of a primary amine, a reaction that is typically complicated by over-alkylation when amines are alkylated with halides in solution. However, since the reactive bromoacetamide is immobilized to the solid support, any over-alkyla-tion side-products would be the result of a cross-reaction with another immobilized oligomer (slow) in preference to reaction with an amine in solution at high concentration (fast). Thus, in the sub-monomer method, the solid phase serves not only to enable a rapid reaction work-up, but also to isolate reactive sites from... 

Fig. 17 (a) Elastin-based stimulus-responsive gold nanoparticles. Reproduced from [131] by permission of The Royal Society of Chemistry (b) Functionalization of a glass surface with ELP. In the first step, the glass surface is aminosilylated with N-2-(aminoethyl)-3-aminopropyl-trimethoxysilane, then modified with glutaraldehyde. Subsequently, the stimulus-responsive biopolymer is covalently immobilized using reductive amination. Reproduced from [132] by permission of The Royal Society of Chemistry... 

In another investigation, ELP[V5L2G3-90] with three lysines in the N-terminal region was immobihzed on a glass surface in a microreactor to enable temperature-controlled positioning of ELP fusion proteins. For this purpose, the glass surface was first functionalized with A -2-(aminoethyl)-3-aminopropyltrimethoxysilane, followed by glutaraldehyde treatment and reductive amination to immobilize the biopolymer on the surface (Fig. 17b) [132]. 

TABLE 10 Results of Fluorescent and Gravimetric Measurements of DNA Hybridization Against a Reference Containing only LB-Immobilized Single-Stranded DNA/Amine Sandwich... 

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