Selected alkyl derivatives

The alkyl derivatives of thiazoles can be catalytically oxidized in the vapor phase at 250 to 400°C to afford the corresponding formyl derivatives (21). Molybdenum oxide, V2O5, and tin vanadate are used as catalysts either alone or with a support. The resulting carbonyl compounds can be selectively oxidized to the acids. 

Other approaches to inhibiting intramolecular cycli2ations of erythromycin have also proven successhil. Erom a series of O-alkyl derivatives of erythromycin, clarithromycin (6-0-methylerythromycin) (37) was selected for clinical development (146,147). Another approach replaced the C-8 proton of erythromycin with duorine, which was accompHshed by both chemical and bioconversion methods to yield durithromycin (38) (148). 

A number of examples of monoacylated diols produced by enzymatic hydrolysis of prochiral carboxylates are presented in Table 3. PLE-catalyzed conversions of acycHc diesters strongly depend on the stmcture of the substituent and are usually poor for alkyl derivatives. Lipases are much less sensitive to the stmcture of the side chain the yields and selectivity of the hydrolysis of both alkyl (26) and aryl (24) derivatives are similar. The enzyme selectivity depends not only on the stmcture of the alcohol, but also on the nature of the acyl moiety (48). 

The ease of oxidation varies considerably with the nature and number of ring substituents thus, although simple alkyl derivatives of pyrazine, quinoxaline and phenazine are easily oxidized by peracetic acid generated in situ from hydrogen peroxide and acetic acid, some difficulties are encountered. With unsymmetrical substrates there is inevitably the selectivity problem. Thus, methylpyrazine on oxidation with peracetic acid yields mixtures of the 1-and 4-oxides (42) and (43) (59YZ1275). In favourable circumstances, such product mixtures may be separated by fractional crystallization. Simple alkyl derivatives of quinoxalines are... 

The case of butane is noteworthy since the selectivity at low conversions indicates that there is no selectivity in the overall hydrogenolysis step between n- and sec-butyl zirconium surface intermediates, while earUer studies had shown that the -alkyl zirconium complexes were more stable than sec-alkyl derivatives (Table 3 and Scheme 23) [94]. 

Large pore zeolites have been used for selective alkylation of diphenyl with propylene to 4,4 -diisc>propyl diphenyl with good selectivity. Similarly, naphthalene gives to 2,6 derivative. 

The initial C-0 bond cleavage (by attack of a/the bromide ion at the benzylic carbon, followed by recyclization of the intermediate 301 by selective alkylation at sulfur) was suggested to be responsible for a stereospecific rearrangement of 2-substituted-1,3,2 -oxazaphospholidine-2-thiones 299 derived from (-) pseudoephedrine into... 

In this chapter we review published results of studies of the kinetics and products of stepwise nucleophilic substitution and elimination reactions of alkyl derivatives, and we present a small amount of unpublished data from our laboratory. Our review of the literature is selective rather than comprehensive, and focuses on work that provides interesting insight into the factors that control the rate constant ratio ks/kp for partitioning of carbocations, and that provides an understanding of how the absolute rate constants ks and kp that constitute this ratio change with changing carbocation structure. 

Two other myo-inositol derivatives have been selectively alkylated. Reaction of DL-l,2 4,5-di-0-cyclohexylidene-myo-inositol with benzyl chloride-potassium hydroxide in benzene, followed by removal of the acetal groups, gave DL-1-O- and DL-4-O-benzyl-myu-inositol in the ratio of 5 2, whereas, under similar conditions, DL-1,2 5,6-O-cyclohexylidene-myo-inositol gave311 the same ethers in the ratio of 57 10. These results are not readily explicable in the absence of knowledge of the conformations adopted by the cyclic acetals. 

Orthophosphoric and benzylphosphonic acids have been selectively alkylated with triethyl phosphite in a new synthesis of mono-, di-, and triethyl phosphates and of mono- and di-methyl phosphonates.62 A-Methylol carboxamides and sulphonamides react with trialkyl phosphites to give the phosphonate derivatives (78) and (80), respectively.63 However, the mechanism appears to be quite different in each case while the carboamides react by a transesterification-rearrange-ment pathway, the sulphonamides undergo elimination-addition via the imine (79). 

Alkylation of P-dicarbonyl compounds and p-keto esters occurs preferentially on the carbon atom, whereas acylation produces the 0-acyl derivatives (see Chapter 3). There are indications that C- and 0-alkylated products are produced with simple haloalkanes and benzyl halides, but only C-alkylated derivatives are formed with propargyl and allyl halides [e.g. 90]. Di-C-alkylation frequently occurs and it has been reported that the use of tetra-alkylammonium 2-oxopyrrolidinyl salts are more effective catalysts (in place of aqueous sodium hydroxide and quaternary ammonium salt) for selective (-90%) mono-C-alkylation of p-dicarbonyl compounds [91]. 

The hydrogen transfer photosensitization has been applied to the diastereo-selective alkylation of chiral fumaric acid derivatives, where again the mild conditions of the photochemical method are advantageous (Figure 3.8). ... 

The key intermediates 692 required for the thermal cyclization were prepared from the readily available indole-2,3-diones 693. The condensation of 693 with 3-methyl-4-phenylbut-3-en-2-one (694) afforded the 3-hydroxy derivatives 695. The dehydration of 695, followed by selective reduction of the 3,1 -double bond of compounds 696, provided the 3-alkyl derivative 697. Finally, the compounds 697 were transformed to the 3-(l,3-butadienyl)indoles 692 by reaction with an excess of ethyl chloroformate (Scheme 5.62). 

N-Alkylation is promoted by prior conversion of the pyrimidinones into their respective silyl ethers. Besides selectivity in the alkylation reactions, silylation confers solubility on molecules which otherwise may be difficult to dissolve in nonhydroxylic organic solvents. Selective N-3-alkylation of uracils requires initial protection of N-1. The alkylation of tautomeric thiones invariably proceeds to give an A-alkyl derivative any N-, 0-, or C-alkylation is less rapid and can be avoided. 

An improved procedure for the selective alkylation of 2,4-quinazolinediones at the 1-position via the 2,4-bistri-methylsilyloxy derivatives has been developed <20030PD700>. This procedure enabled a large-scale synthesis of the aldose reductase inhibitor FK366 28 from the bistrimethylsilyloxy quinazoline 27 (Scheme 2). 

The construction of the oiganometallic dendron required two synthetic transformations. Selective alkylations of the phenolic hydroxyl groups in the presence of potassium carbonate and I8-crown-6 afforded the ether dimetallic derivative 35. This first generation benzyl alcohol 35 was converted to the benzyl bromide 36 by... 

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