Fluorinated ethoxide

A fluormated enol ether formed by the reaction of sodium ethoxide with chlorotnfluoroethylene is much less reactive than the starting fluoroolefin To replace the second fluorine atom, it is necessary to reflux the reaction mixture. The nucleophilic substitution proceeds by the addition-elimination mechanism [30] (equation 26). 

The effect of the leaving group is illustrated in the comparison of fluoro- and chloro-nitrobenzenes (Table VIII) in their reactions with ethoxide ion (lines 5 and 8) and with piperidine (lines 7 and 9). Rate ratios F Cl are 23 1 (opposing and entropy of activation changes) and 201 1 (E effect), respectively, for the two nucleophiles. For the reasons discussed in Section II, D, 1, a fluorine substituent produces a lower energy of repulsion of the nucleophile and thus facilitates reaction. 

Fuchigami and co-workers utilized the regioselective anodic fluorination of aryl propargyl sulfides 301 for the preparation of fluorinated alkyne intermediates, which were subsequently isomerized by sodium ethoxide to furnish 1-fluoro-l-arylthioallenes 302 (Scheme 8.80) [166]. 

Various /i-oxo esters are fluorinated by perchloryl fluoride in the presence of sodium ethoxide, while the fluoro products 8 are usually converted into a-fluoro esters 9 various saturated and unsaturated long-chain esters, e.g. 10 and 11, can be prepared in high yield.23-24... 

A chlorocarbonyl group ortho to a fluorine atom activates the halogen towards nucleophilic displacement. In the synthesis of a number of polyfluorinated chromones the 1,3-diketo side-chain is introduced using ethyl acetoacetate in the presence of magnesium ethoxide. Cyclization occurs on addition of sulfuric acid (70JOC930). 

Dehydrohalogenation sometimes leads to cyclization which gives cycloalkanes or heterocycles. The fluorinated diester 1 has proved to be a convenient source of polyfluoroalkylated cyclopropanes. Reaction of 1 with aqueous potassium hydroxide gives 2- HA //-hepta-fluorobutyl)cyclopropane-l, 1 -dicarboxylic acid (2) in quantitative yield.120 The diethyl ester 3 ot this acid is obtained in a yield of 87% by the reaction of 1 with sodium ethoxide in anhydrous ethanol.120... 

Replacement of fluorine by alkoxy groups also takes place in fluorinated bicyclic alkenes. Hexafluorobicyclo[2.2.0]hexa-2,5-diene (32) when treated with sodium ethoxide in ethanol gives two diethoxy-substituted products.79... 

The first attempts to prepare cobalt and nickel ethoxides were reported in 1936 by Meerwein [1102] and Kandelaki [875]. Application ofNaOR in the exchange reactions could not, however lead to the obtaining of the pure products of purpose as they were insoluble in the parent alcohol. Application of LiOR for this purpose permitted Adams et al. in 1966 to obtain the individual M(OMe)2 — derivatives of id-transition elements in the series from Cr to Cu [6]. In the 1980s Mehrotra et al. have described the homologous series of Ni(OR)2 — from methoxide to r-hexyloxide [99], and also Co(OR)2, where R = Me,Et, Pr [1108]. On the alkoxylation of CoH(N2)(PPh3)3 by esters, phenol, or fluorinated ketones, Hayashi et al. [720] have obtained a series of tetrahedral [Co (OR)(PPh3)3] complexes. 

Kinetic studies of the substitution reaction of 2-chloro-l-methylpyridinium iodide with phenoxides are consistent with the SnAt mechanism, with rate-determining nucleophilic attack.38 The effects of a variety of ring substituents on the reactivities of 2-fluoro- and 2-chloro-pyridines in reactions with sodium ethoxide in ethanol have been examined. The results were discussed in terms of the combination of steric, inductive, and repulsive interactions.39 Substitution in 2,4,6-trihalopyridines normally occurs preferentially at the 4-position. However, the presence of a trialkylsilyl group at the 3-position has been shown to suppress reaction at adjacent positions, allowing substitution at the 6-position.40 Methods have been reported for the introduction and removal of fluorine atoms for polyfluoropyridines. Additional fluorine atoms were introduced by metallation, chlorination, and then fluorodechlorination, while selective removal of fluorine was achieved by reduction with either metals or complex hydrides or alternatively by substitution by hydrazine followed by dehydrogena-tion-dediazotization.41... 

The initially formed carbanion is (25), from which preferential replacement of chloride over that of fluoride ion gives (26). Further attack could give (27), which is stabilized by a-chlorine, rather than (31), which is stabilized by an a-ethoxy group, and (28) is expected to be formed by the loss of the less basic fluoride. Further attack on (28) would give (29), which is stabilized by a-chlorine, preferentially to (32), which is stabilized by a-fluorine, and the loss of fluoride rather than ethoxide ion will give the triether (30). Since this ether is the final product of the reaction... 

The effect of j3-substituents (Park et al., 1965) is demonstrated by the reactions of 1,2,3-trichlorotrifluorocyclobutene (35) with sodium ethoxide. While stabilization by a-chlorine is common to both carbanions (36 and 37) formed by attack at the two vinylic positions, (36) is stabilized by j8-chlorine and j3-fluorine, and (37) by two j3-fluorine atoms. Assuming... 

In order to prepare 5-fluoro-2-pentanone by the acetoacetate synthesis, the experimenter alkylated ethyl acetoacetate with l-chloro-2-fluoro-ethane in the presence of sodium ethoxide in ethanol. Instead of the expected ethyl 3-ethoxycarbonyl-5-fluoro-2-pentanone, he obtained a fluorine-free compound. What was this product, and how was it formed ... 

The clue to the reaction is the polarity of the double bond. The lowest electron density is at the carbon linked to hydrogen, and is due to the strong inductive effect of the difluoromethylene groups and a slight effect of the vinylic chlorine. The attacking species, ethoxide anion, which is in an equilibrium with hydroxide ion in alcoholic potassium hydroxide, reacts in an SN2 reaction by joining the carbon bonded to hydrogen. The subsequent shift of the double bond facilitates ejection of fluorine as an anion and leads to an ether, compound O [77]. 

In the presence of an excess of potassium ethoxide, the ethoxide anion joins the less negative end of the double bond. Strong electron back-donating power of fluorine increases negativity at the carbon linked to chlorine and causes the addition of the ethoxide ion to the carbon linked to fluorine. Subsequent ejection of fluoride anion restores the double bond, and the final product is a diether, compound P [7/J. 

The double bond in l,4-dibromohexafluoro-2-butene surrounded by fluorines and difluoromethylene groups is prone to undergo a nucleophilic addition of ethanol. From the addition product, hydrogen bromide is eliminated in the alkaline medium by E2 mechanism, and the compound C6H5BrF60 is formed. Another explanation of the reaction is addition of ethoxide anion followed by elimination of bromide anion [76],... 

The double bond in chlorotrifluoroethylene is polarized by back-donation of electrons of fluorine in such a way that the negative charge is on the carbon linked to chlorine and fluorine. Consequently, the difluorome-thylene end of the double bond is more electrophilic and is attacked by the ethoxide anion. Subsequent ejection of fluoride anion gives an unsaturated intermediate, l-chloro-l,2-difluoro-2-ethoxyethylene, compound V. This compound reacts with another ethoxide anion in a similar way and yields l-chloro-2,2-diethoxy-1-fluoroethylene. Nucleophilic addition of a third molecule of ethanol gives the final product, the orthoester of chlorofluoroacetic acid, compound W [75]. 

Fluorination of active-methylene compounds. The Pennsalt groups treated diethyl malonate with two equivalents of sodium ethoxide in ethanol and passed in perchloryl fluoride with cooling and reported isolation of diethyl difluoromalonate in... 

In the displacement reaction with sodium ethoxide, the 4-chloro group in ethyl 4-chloro-6-flu-oro-7-(4-tolylsulfanyl)pyrido[2,3-r]pyridazine-3-carboxylatc (2) shows the higher reactivity compared to the fluorine in the 6-position (compare also the reaction with amines below), although the 4-ethoxy compound 5 is obtained in only 30% yield.9... 

---