Synthesis liquid-phase

Scheme 2 Liquid-phase synthesis of DHPM derivatives 7a-f...

Since nanoscale metal nanoparticles are applicable to a number of areas of technological importance, the nano-structured materials chemistry will occupy much attention of scientists. It is certain that controlling the primary structures of metal nanoparticles, that is, size, shape, crystal structure, composition, and phase-segregation manner is still most important, because these structures dominate the physical and chemical properties of metal nanoparticles. Now the liquid phase synthesis facilitates the precise control of the primary structures. 

Geckeler, K, E, Soluble Polymer Supports for Liquid-Phase Synthesis. VoL 121, pp. 31-80. Gehrke, S, H. Synthesis, Equilibrium Swelling, Kinetics Permeability and Applications of Environmentally Responsive Gels. Vol. 110, pp. 81 -144. de GenneSy P.-G> Flexible Polymers in Nanopores. VoL 138, pp. 91-106. 

Suitable soluble polymers for liquid-phase synthesis can be described as follows their molecular weight is high enough for them to be crystalline at room temperature, they bear functional groups on their end termini or side chains, but in contrast... 

Fig. 7.4 Soluble polymers utilized in liquid-phase synthesis.

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

A related support frequently used for liquid-phase synthesis is methoxy-polyethyl-ene glycol (MeO-PEG). The group of Taddei has presented a general procedure for... 

Wu and Sun have presented a versatile procedure for the liquid-phase synthesis of 1,2, ,4-tctrahydro-/i-carbolines [77]. After successful esterification of the MeO-PEG-OH utilized with Fmoc-protected tryptophan, one-pot cyclocondensations with various ketones and aldehydes were performed under microwave irradiation (Scheme 7.68). The desired products were released from the soluble support in good yields and high purity. The interest in this particular scaffold is due to the fact that the l,2,3,4-tetrahydro-/f-carboline pharmacophore is known to be an important structural element in several natural alkaloids, and that the template possesses multiple sites for combinatorial modifications. The microwave-assisted liquid-phase protocol furnished purer products than homogeneous protocols and product isolation/ purification was certainly simplified. 

Scheme 7.69 Liquid-phase synthesis of quinoxalin-2-ones.

Utilizing the same aryl fluoride linker on conventional MeOPEG polymer, these authors also presented a microwave-accelerated liquid-phase synthesis of benzimidazoles (Scheme 7.70) [79]. This bicydic pharmacophore is an important and valuable structural element in medicinal chemistry, showing a broad spectrum of pharmacological activities, such as antihistaminic, antiparasitic, and antiviral effects. 

Scheme 7.71 Liquid-phase synthesis of chiral quinoxalinones.

In a closely related study, Tung and Sun discussed the microwave-assisted liquid-phase synthesis of chiral quinoxalines [80], Various L-a-amino acid methyl ester hydrochlorides were coupled to MeOPEG-bound ortho-fluoronitrobenzene by the aforementioned ipso-fluoro displacement method. Reduction under microwave irradiation resulted in spontaneous synchronous intramolecular cyclization to the corresponding l,2,3,4-tetrahydroquinoxalin-2-ones (Scheme 7.71). Retention of the chiral moiety could not be monitored during the reaction, but after release of the desired products it was found that about 10% of the product had undergone racemization. 

Scheme 7.74 Liquid-phase synthesis of 1,3-disubstituted thioxotetrahydropyrimidinones.

Geckeler, K. E. Soluble Polymer Supports for Liquid-Phase Synthesis. Vol. 121, pp. 31-80. 

The Suzuki coupling of soluble polyethylene glycol (PEG)-bound bromothiophene 71 and p-formylphenylboronic acid provided biaryl 72 [56]. Due to the high solubilizing power of PEG, the reaction was conducted as a liquid-phase synthesis. Treatment of 72 with o-pyridinediaminc resulted in a two-step-one-pot heterocyclization through an imine intermediate. Nitrobenzene served as an oxidant in the ring closure step. Finally, transesterification with NaOMe in MeOH resulted in l//-imidazole[4,5-e]pyridine 73. 

YH Wang, JC Xu. One-pot liquid-phase synthesis of DSIP and 5-DSIP using fluoren-9-ylmethoxycarbonyl-protected amino acid pentafluorophenyl esters. (3-diethylami-nopropane-2-ol) Synthesis 845, 1990. 

Selected examples of the liquid-phase synthesis of 4-tolyl sulphones... 

Liquid phase synthesis of alkyl 4-toIyl sulphones... 

Initially, the term Hquid-phase synthesis was used to contrast the differences between soHd-phase peptide synthesis and a method of synthesis on soluble polyethylene glycol (PEG) [5, 6]. Although soluble polymer-supported synthesis is less ambiguous than Hquid-phase synthesis, the latter term is more prevalent in the Hterature. In-keeping with previous reviews [7-12], the phrases classical or solution synthesis will be used to describe homogeneous reaction schemes that do not employ polymer supports while liquid-phase synthesis will be reserved... 

Traditionally, soluble polymers have received less attention as polymeric supports than their insoluble counterparts. A perceived problem with the use of soluble polymers rested in the ability to isolate the polymer from all other reaction components. Yet, in practice this separation is not difficult and several methods have capitalized on the macromolecular properties of the soluble support to achieve product separation in liquid-phase synthesis. Most frequently the homogeneous... 

A frequent complication in the use of an insoluble polymeric support lies in the on-bead characterization of intermediates. Although techniques such as MAS NMR, gel-phase NMR, and single bead IR have had a tremendous effect on the rapid characterization of solid-phase intermediates [27-30], the inherent heterogeneity of solid-phase systems precludes the use of many traditional analytical methods. Liquid-phase synthesis does not suffer from this drawback and permits product characterization on soluble polymer supports by routine analytical methods including UV/visible, IR, and NMR spectroscopies as well as high resolution mass spectrometry. Even traditional synthetic methods such as TLC may be used to monitor reactions without requiring preliminary cleavage from the polymer support [10, 18, 19]. Moreover, aliquots taken for characterization may be returned to the reaction flask upon recovery from these nondestructive... 

Fig. 5.1 Soluble polymers used as supports for liquid-phase synthesis.

Scheme 10.6 General strategy for the liquid-phase synthesis of disaccharides using glycosidases.

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