Fluorinations 2- benzoate

Mouttaki H, Nanny MA, Mclnerney MJ. Metabolism of hydroxylated and fluorinated benzoates by Syntrophus aciditrophicus and detection of fluorodiene metabolite. Appl Environ Microbiol. 2009 75 998-1004. 

The trifluoroacetate analogue of [Ru2(02CR)2(C0)4]n was synthesized by Petrukhina et al. [68]. These were obtained by gas phase sublimation of the crude product from the reaction of Ru3(CO)i2 and trifluoroacetic acid in a DCM/benzene mixture. The solid state study of [Ru2(02CCF3)2(C0)5]2 (2) (Scheme 3) reveals a dimer of dimer structure. Petrukhina and Davies also reported a variety of mixed carbonyl/fluorinated benzoates of diruthenium(l,l) obtained via melt reactions of Ru3(CO)i2 with appropriate carboxylic acids (3-9) [69]. Compounds 3-6 show a... 

In 1998, Ube Industries, Ltd. discovered that pentafluorobenzoates, such as methyl pentafluorobenzoate (62), can be used as additives in small quantities [92], Also, in 1999, Toyota Central R D Labs found that fluorinated benzoates, such as methyl 2,6-difluorobenzoate (63), can be used as additives in small quantities [93], and in 2002, Ube Industries, Ltd. found that pentafluorophenol compounds, such as pentafluorophenyl methanesulfonate (64) and methyl pentafluorophenyl carbonate (65), can be used as additives in small quantities [94]. 

The metabolism of fluorobenzoates has been examined over many years. Early studies using Nocardia erythropoUs (Cain et al. 1968) and Pseudomonas fluorescens (Hughes 1965) showed that although the rates of whole-cell oxidation of fluorobenzoates were less than for benzoate, they were comparable to, and greater than for, the chlorinated analogs. As for their chlorinated analogs, both dioxygenation and hydrolytic pathways may be involved, and studies have revealed that the different pathways depended on the positions of the fluorine substituents. 

A contrasting pathway was found for the metabolism of 2-fluoro-4-nitrobenzoate by Nocardia erythropolis that does not involve loss of fluorine concomitant with decarboxylation (Cain et al. 1968). The pathway (Figure 9.30) therefore differs from what has subsequently emerged as the principal pathway for metabolism of nonhydroxylated 2-halogenated benzoates. 

Engesser KH, MA Rubio, DW Ribbons (1988a) Bacterial metabolism of side chain fluorinated aromatics cometabolism of 4-trifluoromethyl (TFM)-benzoate by 4-isopropylbenzoate grown Pseudomonas putida IT strains. Arch Microbiol 149 198-206. 

Genther BRS, GT Townsend, PJ Chapman (1990) Effect of fluorinated analogues of phenol and hydroxyben-zoates on the anaerobic transformation of phenol to benzoate. Biodegradation 1 65-74. 

The Arbuzov reaction has been applied for the synthesis of fluorinated carbohydrates. 1,2 3,4-Di-O-isopropylidene-a-D-galactopyran-ose 6-(N,N-diethyl-P-methylphosphonamidite) was treated with ethyl fluoroacetate, to afford 6-deoxy-6-fluoro-l,2 3,4-di-O-isopropylidene-a-D-galactopyranose in 19% yield.241 The corresponding 6-deoxy-6-fluoride was obtained in 60% yield by treatment of l,2 3,4-di-0-isopropylidene-a-D-galactopyranose 6-(dipropylphosphinite) with hexafluoropropene.242 The mechanism of this reaction has been discussed.243,244 In contrast, treatment of 1,2 -.3,4-di-O-isopropylidene-a-D-galactopyranose 6-(tetraethylphosphorodiamidite) with benzoyl fluoride yielded the corresponding 6-benzoate, not the 6-deoxy-6-flu-oride expected.245... 

Scheme 3.37 describes gas-phase generation of m-benzyne anion (the distonic anion-biradical) from m-bis(trimethylsilyl) benzene (Wenthold et al. 1994, 1996 Wenthold and Squires 1998). The same anion-biradical is formed from isophthalic acid under the same conditions (Reed et al. 2000). Particularly, the reaction of m-bis(trimethylsilyl) benzene with fluoride ion, followed by treatment of the formed trimethylsilyl phenyl anion with fluorine in helium, produces the anion-biradical mentioned. The latter is transformed into the corresponding nitro benzoate anion through the addition of CO2 and NO2 (Scheme 3.37). 

Synthesis of the thymidine derivative relies on the older two-step insertion of fluorine. Thus, the hydroxyl group in 3 -deoxythymidine benzoate (51-1) is first converted to the mesylate (51-2). Reaction with potassium fluoride in hydrogen fluoride replaces the mesylate by fluorine (51-3). The fact that this reaction, as that above, proceeds with retention of the configuration mles out simple displacement as the mechanism for this transform. The presence of the methyl group at position 5 negates the need for the chlorination step. Saponification then affords the antiviral agent alovudine (51-4) [52]. 

The same study has shown that the organization completely changes for the corresponding benzoic acid 23 (Fig. 10) where the COOH groups form cyclic dimers with a linear shape.10 In this case there is no interdigitation of the Rp-chains and a (tilted) double layer structure is formed (see Fig. 11c), which is in line with the dll ratio of 1.6-1.7 observed for these benzoic acids. Related types of LC structures have been discussed for other partly fluorinated 4-alkoxybenzoic acids [126], and succinimidyl benzoates 24 [121]. 

Fig. 16 Representative examples of semiperfluorinated benzoic acids and methyl benzoates with fluorinated chains (77°C) [126, 133, 134, 136, 144-146]...

The difference in the rate of benzoate and acetate solvolysis is sufficient to enable selective removal of acetates in the presence of benzoates. Typical conditions include magnesium methoxide in methanol [Scheme 4.336],608 guanidine in methanol-dichloromethane,610 and fluoroboric acid in methanol.638 Fluorine substitution on benzoyl groups increases hydrolytic lability.63 ... 

The fluorination of aromatic compounds in inert solvents, such as acetonitrile, carbon tetrachloride, and Freons, with dilute elemental fluorine (0.76 % to 12% in N2) at temperatures ranging from —78 to —25 C results in the controlled substitution of hydrogen by fluorine.IS1 155 The distribution of products indicates an electrophilic process, for example the fluorination of methyl benzoate at — 20 C in acetonitrile with diluted fluorine (10% in N2) results in the formation of fluorobenzoates 1-3 and unidentified tars. 

Particular attention has been devoted this year to the study of fluorinated aryl azides. This interest stems from their potential use as photoaffinity probes due to the ease with which perfluorophenyl nitrene undergoes C-H bond insertion. Perfluorin-ated azide derivatives of methyl benzoate afford photochemically... 

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