Rapid synthetic method

The development of fast, reliable and convenient chemical processes is important for the whole field of organic chemistry. In fact, in many cases even a slight drop in chemical yield is acceptable when compensated for by large gains in reaction time or improved ease of handling [12-15]. These features apply in particular to iterative reaction optimization in commercial situations where the reaction time is an important parameter [16]. In particular, the pharmaceutical industry is continuously on the look-out for new rapid synthetic methods and strategies for the discovery and development of new drugs. 

Combinatorial synthesis has prompted an interest in rapid synthetic methods, particularly in the area of SPS and its application to the high-speed automated synthesis (Seneci, 2000). In solid-phase combinatorial synthesis, reagents can be used in excess without separation problems to attain complete conversion. Facile purification and automation provide further advantages. Two approaches for combinatorial synthesis of oligonu-clotides/peptides/saccharides will be considered. 

Qindamycin, 7(5)-7-chloro-7-deoxyliQcomycin [18323-44-9] (1, R = H, R = Q), also known as Cleocin, first resulted from the reaction of lincomycin and thionyl chloride (54) improved synthetic methods involve the reaction of lincomycin and triphenylphosphine dichloride or triphenylphosphine in carbon tetrachloride (55). Clindamycin is significantly more active than lincomycin against gram-positive bacteria in vitro, and is absorbed rapidly following oral adnainistration. Clindamycin 2-palmitate [36688-78-5], (6, R = R = OC(CH2) 4CH2), 2-palmitate ester of clindamycin, is... 

The procedure which had originally been used by Lehn et al. involved slow addition (over a period of ca. 8 h) of ca. 0.1 M solutions of diamine and diacyl halide in benzene. Dye et al. found that the reactions could be conducted more rapidly as long as stirring was kept efficient. This observation suggested the use of a mixing chamber of the type normally used for stopped-flow kinetic studies. Utilizing this type of set-up, the latter authors were able to obtain a 70% yield for 1, slightly inferior to the yield reported by Lehn, but a similar yield of 3 which is better than that previously ob-tained. Note that the chemical features of this synthetic method are essentially identical to the approach shown in Eq. (8.1) and differ primarily in the mechanics. 

Combinatorial chemistry, a new chapter of organic synthesis, is now developing rapidly. This new approach to synthesizing large designed or random chemical libraries through application of solid phase synthetic methods, promises to revolutionize the process of drug discovery in the pharmaceutical industry.24... 

The imidazole ring is a privileged structure in medicinal chemistry since it is found in the core structure of a wide range of pharmaceutically active compounds efficient methods for the preparation of substituted imidazole libraries are therefore of great interest. Recently, a rapid synthetic route to imidazole-4-carboxylic acids using Wang resin was reported by Henkel (Fig. 17) [64]. An excess aliphatic or aromatic amine was added to the commercially available Wang-resin-bound 3-Ar,M-(dimethylamino)isocyano-acrylate, and the mixture was heated in a sealed vial with microwave irradi-... 

The data presented in Figure 8 graphically illustrate the tremendous and rapid growth in interest in FOSS chemistry, especially for patented applications. This looks set to continue with current applications in areas as diverse as dendrimers, composite materials, polymers, optical materials, liquid crystal materials, atom scavengers, and cosmetics, and, no doubt, many new areas to come. These many applications derive from the symmetrical nature of the FOSS cores which comprise relatively rigid, near-tetrahedral vertices connected by more flexible siloxane bonds. The compounds are usually thermally and chemically stable and can be modified by conventional synthetic methods and are amenable to the usual characterization techniques. The recent commercial availability of a wide range of simple monomers on a multigram scale will help to advance research in the area more rapidly. 

The interesting complex chemistry of rhodium has been rather neglected this is probably because most of the synthetic methods for obtaining complexes have been tedious. In general, substitutions of chlorine atoms bonded to rhodium by other ligands are slow, and products have usually been mixtures. The situation is now changing, since novel catalytic approaches to rhodium complexes have been developed.1 The catalysis in the present synthesis involves the rapid further reaction of the hydrido complex formed from l,2,6-trichIorotri(pyridine)rho-dium(III) in the presence of hypophosphite ion. 

The last two decades have witnessed rapid development of organic synthetic methods based on benzotriazole derivatives. Thus, introduction of benzotriazole moiety to organic molecules provides several practical advantages. Among other benefits, a benzotriazolyl substituent activates the reaction center, stabilizes intermediates, increases regio- and stereoselectivity, and simplifies separation and purification of the products. After the desired molecular assembly is constructed, the bond with benzotriazole is cleaved off to provide the final product. A vast variety of... 

Rhodium Porphyrins. Chemical syntheses of [CPDRh32 and (P)Rh(R) complexes are well known(4-11). Electrochemical techniques have also been used to synthesize dimeric metal-metal bonded [(TPP)RhJ 2 as well as monomeric metal-carbon a-bonded (TPP)Rh(R) and (0EP)Rh(R)(12-16). The electrosynthetic and chemical synthetic methods are both based on formation of a highly reactive monomeric rhodium(II) species, (P)Rh. This chemically or electrochemically generated monomer rapidly dimerizes in the absence of another reagent as shown in Equation 1. 

Because of their simplicity, easy-to-carry-out, low requirement of prepurification, and rapidity, TLC methods have been frequently applied in the analysis of synthetic dyes. However, the majority of invetigations were performed in model systems to establish the optimal separation conditions, and to determine various physicochemical parameters of dyes. The number of studies dealing with the analysis of dyes in complicated natural accompanying matrices is relatively low. 

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... 

Also reactions that rapidly create more diversity are sought after. In recent years, more and more multicomponent reactions (MCRs) have been developed and combined with modern synthetic methods such as RCM or Pd couplings to provide rapid access to complex, natural product-like structures in solution. 

Pyridine and its derivatives are technically-important fine chemicals. Their isolation from coal tar is decreasing, whereas their manufacture by synthetic methods has increased rapidly. The classical pathways to pyridine have been discussed by Abramovitch (74HC14-1-4). Many of them rely on the reaction of aldehydes or ketones with ammonia in the vapor phase. However, the condensation processes used suffer from unsatisfactory selectivity. Using soluble organocobalt catalysts of the type [YCoL] allows pyridine and a wide range of 2-substituted derivatives to be prepared selectively and in one step from acetylene and the appropriate cyano compound [Eq.(l)]. 

Asymmetric synthesis has evolved rapidly during recent years. Most of the progress is registered in synthetic methods less emphasis has been given to theoretical concepts and mechanistic studies. Methods have been devised for achieving optical yields exceeding 95%. A number of stochiometric reactions with respect to the chiral auxiliary moiety are now highly efficient. 

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