Schiff bases fluorination

Tnfluoromethyl hypofluonte will fluorinate Schiff bases, giving N,a,a-tn-fluoroatmnes and a-fluoroimines [144] and reacts with diazoketones to give adducts in modest yields [145] (equation 6) At-Substituted aziridines give nng opened products by 1,3 addition of fluonne on nitrogen and trifluoromethoxy on carbon [146] (equation 7)... 

For the tin(II) complexes of the fluorinated Schiff bases derived from amino acids, [47] the 5119Sn chemical shifts in the range from -575 to 582 ppm suggested the four-coordinate square-planar geometry.111... 

Cycloaddition may be varied by the use of fluorinated thioketenes in place of ketenes. Olefins and Schiff bases serve as the other component. Thus thioketene 56 cycloadds to a SchifT base to give product 57 in a 79% yield. In a further variation, reaction of dithiobenzoate esters with diphenylketene yields 61% of product 58. ... 

The first step of the enzymatic process is the transaldimination of the Schiff base lysine-PLP by the amino acid. The pulling out of the proton in a of the fluorinated amino acid is accompanied by elimination of a fluorine atom of the CX2F group, thus affording a very reactive quinonic species. This latter one can further react with a nucleophilic entity of the enzyme (e.g., the lysine of the active site) ( Michael addition inactivation process ) (Figure 7.47). ... 

Very detailed studies on the inhibition of alanine racemase by fluoroalanines have been conducted. This enzyme catalyzes the racemization of alanine to provide D-alanine, which is required for synthesis of the bacterial wall. This work has demonstrated that a more complex process than that represented in Figure 7.47 could intervene. For instance, in the case of monofluoroalanine, a second path (Figure 7.48, path b) occurs lysine-38 of the active site can also attack the Schiff base PLP-aminoacrylate that comes from the elimination of the fluorine atom. This enamine inactivation process (path b) has been confirmed by isolation and identification of the alkylation compound, after denaturation of the enzyme (Figure 7.48). ... 

Various steroids are fluorinated by conversion into the enolates, followed by fluorination with perchloryl fluoride to give the 16-fluorinated products 16.19 28 The Schiff base of 7-aminodeacetoxyeephalosporanic acid tart-butyl ester is converted into an anion with potassium tm-butoxide,29 while further reaction with perchloryl fluoride diluted with nitrogen at — 50 C gives 7-(benzylideneamino)-7-fluorodeacetoxycephalosporanicacid fer/-butyl ester (17) in high yield. An attempt to prepare 2-fluoropodophyllotoxin by reaction of the enolate with perchloryl fluoride resulted in a violent explosion.30... 

NMR studies have been carried out on Schiff bases derived from pyridoxal phosphate and amino acids, since they have been proposed as intermediates in many important biological reactions such as transamination, decarboxylation, etc.90 The pK.d values of a series of Schiff bases derived from pyridoxal phosphate and a-amino adds, most of which are fluorinated (Figure 11), have been derived from H and19F titration curves.91 The imine N atom was found to be more basic and more sensitive to the electron-withdrawing effect of fluorine than the pyridine N atom. Pyridoxal and its phosphate derivative are shown in Figure 12a. The Schiff base formation by condensation of both with octopamine (Figure 12b) in water or methanol solution was studied by 13C NMR. The enolimine form is favoured in methanol, while the ketoamine form predominates in water.92... 

High yields have been achieved via Schiff base condensation of 2-aminophenol 115 and fluorinated benzaldehyde... 

Recent literature in the chemistry of calixpyrroles comprises the syntheses, characterization and complexation reactions of a series of binucleating Schiff-base calixpyrrole macrocycles <2007CEJ(A)3707> a study of the dynamics of calix[4]pyrrole and octafluorocalix[4]pyrrole as a function of the solvent and fluorine substitution <2007CEJ(A)1108> and oxygen reduction at dicobalt complexes of a Schiff base calixpyrrole ligand <2007AGE584>. 

Depending on the fluorinating reagent used, the reaction of imines leads to different fluorination products. Treatment of Schiff bases with trifluoromethyl hypofluorite gives A,A-difluoro amines under mild reaction conditions however, if the reaction is carried out using A-fluoro-bis(trifluoromethanesulfonyl)amine (TfjNF), a-monofluoro 2 and/or a,a-difluoro ketones 3 are obtained (Table 11). ... 

Both GC and LC behavior of metal complexes of various ligand types including salicy-laldimines and Schiff bases and fluorinated /3-diketones was reported. Metal ions included the lanthanides, transition metals, Pt, Pd and Zn. Dissociation and thermal instabilities were found to be the main limitations in the chromatography of such derivatives. The data indicate that pre-column derivatization and GC is unlikely to provide a viable method for the ultratrace determination of metal ions except in rare circumstances. On the other hand, LC of complexed metal ions was found as a valuable technique that combines the advantages of versatility, specificity and sensitivity with the capacity for simultaneous determination and speciation. Diastereoisomers of oxovanadium(IV) complexes of tetradentate Schiff bases could be resolved by both GC and LC . ... 

Alkylation of the Schiff base of glycine with 2-hydroxy-3-pinanone proceeds in an extremely diastereoselective manner. Thus, fluoro-functionalization on the a-carbon of the Schiff base followed by hydrolysis provides fluorinated a-amino acids in a highly enantiomerically enriched form. 2-Fluoroethylation and 2-fluoroallylation of 157 (see Scheme 9.35) and bromodifluoromethylation of 161 (see Scheme 9.36) give the desired adducts 158 and 162, respectively, with excellent diastereoselectivities. Lithium enolate dimer 160 has been proposed as a reactive intermediate for the stereocontrolled alkylation [61]. The adducts 158 and 162 were transformed to 4-fluoro-2-amino acids (>96% ee) 159 [61] and 3,3-difluoroglutamine 164 [62], respectively. 

Fluorinated R groups (C2F5, C6F5, etc.) enhance thermal stabilities and improve volatilization of salicylaldimines, Schiff bases, /3-diketonates, /3-dithiones, and hexadentate macrocyclic complexes of lanthanides, transition metals, and Zn11 for GC separations.45... 

Key Words Ethylene oxide, Propylene oxide. Epoxybutene, Market, Isoamylene oxide. Cyclohexene oxide. Styrene oxide, Norbornene oxide. Epichlorohydrin, Epoxy resins, Carbamazepine, Terpenes, Limonene, a-Pinene, Fatty acid epoxides, Allyl epoxides, Sharpless epoxidation. Turnover frequency, Space time yield. Hydrogen peroxide, Polyoxometallates, Phase-transfer reagents, Methyltrioxorhenium (MTO), Fluorinated acetone, Alkylmetaborate esters. Alumina, Iminium salts, Porphyrins, Jacobsen-Katsuki oxidation, Salen, Peroxoacetic acid, P450 BM-3, Escherichia coli, lodosylbenzene, Oxometallacycle, DFT, Lewis acid mechanism, Metalladioxolane, Mimoun complex, Sheldon complex, Michaelis-Menten, Schiff bases. Redox mechanism. Oxygen-rebound mechanism, Spiro structure. 2008 Elsevier B.V. 

Fluorine substituents on the aromatic ring in chiral quaternary ammonium salts also play an important role for the improvement of enantioselectivity in asymmetric alkylations of the Schiff base of glycine esters in an aqueous biphase system. Dolling first demonstrated asymmetric methylation of indanone (44) by cinchonidine ammonium salt (43) (Scheme 5.12) [18]. 

Novikov and coworkers described an intramolecular variant of their difluorocar-bene/Schiff base chemistry discussed above. Iminodifluoromethanides derived from the reaction of difluorocarbene with Schiff bases react with tethered acetylenes to produce fluorinated chromeno[4,3-Z ]pyrroles, for example, 78 (Fig. 3.38). ... 

Fluorinated synthons have been used to access fluorinated imidazoles. Reduction of Schiff bases derived from amidines and hexafluoroacetone with SnCl2 gives rise to 5-fluoro-4-trifluoromethylimidazoles 110 (Fig. 3.57). ° ° Because the 5-fluoro substituent is readily displaced by nucleophiles such as alkoxide, cyanide, and others, this procedure provides access to a range of trifluoromefliyl-substituted imidazoles (also see below). 

The fluorinated ligand in the complex 69 could be introduced by a Grignard reaction on 68 with the appropriate reagent. In this context, the significant role of the electronic and steric effects played by both the Schiff base ligand and the other, additional ligand has been clearly evidenced in studies on ROMP and atom transfer rapid polymerization (ATRP) reactions. 

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