4-Fluorophenol, from

In the production of 4-fluorophenol from 4-fluoroaniline (ref. 4a - 4g) a major problem arises with corrosion of glass lined vessels by hydrofluoric acid release. The hydrofluoric acid is considered to arise by nucleophilic displacement of the fluoride from the 4-fluorobenzene diazonium hydrogen sulphate (Fig. 5). This is not surprising since the diazonium group is one of the most electron withdrawing group known. 

The Kc values have been obtained by measuring the equilibrium concentration of 4-fluorophenol from the absorbance of the v(OH) infrared band at 3614 cm by means of a Fourier transform infrared (FTIR) spectrometer. The well-known advantages of FTIR spectrometry over dispersive IR spectrometry, used in the early studies [9,10], should provide more accurate absorbance measurements in a larger domain. Consequently, it is easier to adjust the initial concentrations of 4-fluorophenol and base in order to form the complex of 1 1 stoichiometry almost exclusively and avoid the self-association of 4-fluorophenol and the formation of complexes of higher stoichiometry. Examples of such side-effect... 

NMR was used to study the effect of pH on the hydroxylation of 3-fluorophenol by the hydroxylase from Trichosporon cutaneum, and revealed that the ratio of products as well as the yield was pH-dependent (Peelen et al. 1993). 

The metabolism of fluorophenols by phenol hydroxylase from Trichosporium cutaneum, catechol 1,2-dioxygenase from Pseudomonas arvilla strain C-1, and by the fungus Exophilia jeanselmei has been examined, and detailed NMR data were given for the ring fission flnoromnconates (Boersma et al. 1998). 

Peelen S, IMCM Rietjens, WJH van Berkel, WAT van Workum, 1 Vervoort (1993) F-NMR study on the pH-dependent regioselectivity and rate of the ort/jo-hydroxylation of 3-fluorophenol hy phenol hydroxylase from Trichosporon cutaneum. Eur J Biochem 218 345-353. 

The metabolism of a range of fluorophenols containing up to five fluorine substituents was examined using phenol hydroxylase from Trichosporon cutaneum (Peelen et al. 1995). Fluorocatechols were formed, with loss of fluoride for some substrates. 

Fluorinated Muconates Formed from Fluorophenols by Phenol Hydroxylase and Catechol 1,2-Dioxygenase from Exophilia jeanselmei Fluoromuconate Metabolite Phenolic Substrate(s)... 

Then, nucleophilic aromatic substitution was applied for the synthesis of l,2,4,6,7,9-hexafluoro-l,4-dibenzodioxin from 2,3,4,6-tetrafluorophenol in the presence of sodium /-butylate <1995JFC(73)265>. In a similar way, cyano-1,4-dibenzodioxins and cyano-l,4-dibenzodithiins have been synthesized by fluorine displacement reactions with catechols <2001NJC379, 2001NJC385>. In accordance with a similar mechanism, the synthesis of spiro (l,4-benzodioxin-2,4 -piperidines) 205 and spiro (l,4-benzodioxin-2,3 -pyrrolidines) 206 have been developed from alcohols 207 and 208, respectively, both of them being obtained from 2-fluorophenol 210 with the corresponding epoxide 209 (Scheme 18) <2003SL813>. 

Fluoro-2,4 dinitropbenol, yel ctysts (from petr eth), mp 138—39°. Prepd by stepwise nitration of m-fluorophenol (Refs 1 6) 5 FluorO 2,4-dinitTophenol, lt-yel microcrysts (from petr eth), mp 138—39° v sol in w prepd by nitrating 3 fluorophenol with mixed sulfuric-nitric acid at 10—15° and hydrolizing the reaction prodict with steam (Refs 1 6) P-Fluoro A-dinitropbenoU yel crysts (from aq ale or benzine), mp 102° v sol in benz, MeOH St ale mod sol in w obtd with other products by nitrating 2-fluoroanisole or 2-fluorophenetol with mixed acid at —5 to 0°... 

Fluoro-2,6-dinitTophenof ndls (from petr eth), mp 68-5° was prepd by stepwise nitration of 3 fluorophenol or 5 fluoro-2-nitrophenol at 10-15°(Refs 3 6)... 

Figure 3.9 Reagents and conditions (i) Dean-Stark then BnBr, K2CO3, dibenzo-18-crown-6, acetone, 99% (ii) SOCI2, DMF (cat.), 85% (iii) 4, EtsN, CH2CI2, 65% (iv) (Boc)20, dipea, CH2CI2, 95% (v) Pd/C, H2, CH3OH, 99% (vi) CS2CO3, 3-brotnopropionic acid, acetone, 67 % (vii) aminomethylated polystyrene, DCC, penta-fluorophenol, DMAP (viii) TEA, CH2CI2. Reprinted from reference [3], with permission from Elsevier.

Tangible evidence was found for the in situ production of perfluoro(2,3,4,5-tetrahydro-pyridines) 2, 3, and 4 during the transfer of F- from perfluoro-l-fluoropiperidine (1) to carbanionic sources.22 23 Perfluoro-l-fluoropiperidine (1) was employed to convert triphenyl-phosphane, -arsane, and -stilbane to the difluorides, triphenylphosphorus difluoride, triphenyl-arsenic difluoride, and triphenylantimony difluoride, respectively,24 and sodium phenoxide to 2- and 4-fluorophenol.25 Perfluoro-l-fluoropiperidine (1) reacts with 7V,/V-dimethylaniline, substituting the 0/7/m-hydrogen by fluorine. A similar reaction proceeds with /V,/V-diethylaniline.26... 

Dediazoniation itself is not dramatically dependent on the hydrogen fluoride/pyridine ratio, as shown from the dediazoniation of benzenediazonium tetrafluoroborate (previously isolated) in hydrogen fluoride/pyridine mixtures provided that the hydrogen fluoride/pyridine ratio is larger than 6, fluorobenzene is always obtained in quantitative yield (for hydrogen fluoride/ pyridine ratios below 6, byproducts result from the phenyl cation and free pyridine).10 These observations have resulted in new, very efficient syntheses of 4-fluorophenols 2 involving dediazoniation, in hydrogen fluoride/pyridine mixtures, of crystalline 4-hydroxy benzenediazonium chloride and tetrafluoroborate 3 (formed under anhydrous conditions)89,96 as well as quinone-diazide (formed from aminophenol in tetrafluoroboric acid).93,97 Such methods are more efficient than the Balz-Schiemann reaction under standard conditions. 

Recently, it has been reported that photochemical fluorodediazoniation is improved when a solution of the diazonium tetrafluoroborate in hydrogen fluoride/pyridine (70 30 w/w) mixture is irradiated at 10°C.248 For example, 4-fluoro-3-(trifluoromethyl)anisole is obtained by this method in 95 % yield from the corresponding diazonium tetrafluoroborate. Concerning the synthesis of 4-fluorophenol under similar conditions, the yield is very dependent on the... 

The further question arises, whether P values of compounds in bulk, acting as solvents, are the same as when they are in dilute solutions, acting as solutes. This question was answered in the affirmative in the case of non-associated solvents (Abraham et al. 1989), the solute values having been obtained from hydrogen bonding equilibrium constant data, e.g., for interactions of the solvents as solutes with phenol or 4-fluorophenol in tetrachloromethane diluent. Notwithstanding... 

Deoxygenation of primary and secondary alcohols.1 This deoxygenation has been effected by reduction of the thiocarbonyl esters with tributyltin hydride and AIBN as the radial initiator (11, 550). A newer, milder method uses diphenylsilane in a radical chain reaction initiated by triethylborane and air. Even secondary thiono-carbonates, particularly those derived from 4-fluorophenol, are deoxygenated at 25°. 

The effect of the halogen substituent (fluoro, chloro, bromo and iodo) on the yield and mechanism of 4-halophenol photolysis was investigated by Durand et al. [24], Transient spectroscopy in aerated aqueous solutions indicated the formation of p-benzoquinone O-oxide from each derivative except 4-iodophenol for which no transients were detected p-benzoquinone and hydroquinone were found as photoproducts for all four compounds. It was concluded that the carbene mechanism was valid for the whole series. Under continuous irradiation, the 4-halophenol degradation quantum yields were determined to be

fluorescence lifetimes decreased in the same order, from 2.1 ns for 4-fluorophenol to 0.4 ns for 4-chlorophenol and < 0.1 ns for 4-bromophenol. 

Difunctional compounds, including certain halogenated ethers, aldehydes, ketones, phenols, amines, and nitro compounds, have been prepared by the Sandmeyer reaction. However, fluorophenols and fluoro acids are best obtained from the corresponding ethers and esters, respectively, which have been fluorinated by the Schiemann reaction. ... 

In general, the behavior of the amino moiety in 1 showed no great differences from that of alkylamines or other cycloalkylamines. Cyclopropylamine (77) (pK = 9.10 ) was found to be somewhat less basic than isopropylamine (pK = 10.67 ) further pK values for 77 and other aminocyclopropane derivatives are reported in Refs 347,483 486. Interactions of 77 with p-fluorophenol , propane-2-thiol , H in the presence of 18 crown-6 or Ag have been investigated. For considerations of the protonation of 77 in the gas phase see Refs 491-493. Different basicity was observed for NR2 groups in the exo and endo-posiiion of a [3.1.0] bicyclic system . 

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