2. Processes of replacement of functional groups with fluorine.

2.1. Replacement of oxy-groups with fluorine under the influence of hydrogen fluoride complexes with bases.

Replacement of OH groups with fluorine in alcohols under the influence of anhydrous hydrogen fluoride is not a very smooth reaction due to formation of a variety of side products such as ethers, alkenes, polymers. Besides, aqueous hydrogen fluoride is a highly corrosive substance and only a special apparatus may be used in this case. Under common conditions primary alcohols do not react with anhydrous hydrogen fluoride, but at elevated temperatures or in the presence of catalysts they can be converted to fluoroalkyls [220-224]. For example, methyl fluoride can be obtained in a reaction of methyl alcohol with hydrogen fluoride in gas phase in the presence of aluminium trifluoride (at a temperature of 375-425^oC [225]) or of chromium trifluoride ( 260^oC). At the same time interaction of primary alcohols ( hexanol-1, octanol-1, 2,2-dimethylpropanol-1) with HF/Py complexes or with Et₃N/3HF in the presence of fluorides of alkali metals results in formation of appropriate 1-fluoroalkanes in 30-55% yield [226].

The complexes of HF with bases are used as fluorinating agents for replacement of alcohol oxy-group for alcohols of relatively low reactivity, i.e. for secondary and tertiary alcohols or for benzyl alcohol [2, 227]. The review on using Py* 9HF system ( the Ohle reagent) for replacement of a hydroxy-group in secondary and tertiary alcohols with fluorine has been given in [228].

Secondary and tertiary alcohols interact with anhydrous hydrogen fluoride already at low temperatures (0^oC) to form fluorides of alkyles. But there were observed products related to polymerisation. If the reaction is carried out in the presence of formaldehyde then ethers are formed. So, interaction of (CF₃)₂CHOH with CH₂O in a medium of HF at 60-60^oC results in formation of fluoromethylhexafluoroisopropyl ether FCH₂OCH(CF₃)₂ in 90% yield which is used as anaesthetic [229]. The use of HF/Py complex in a reaction with secondary and tertiary alcohols gives better results (table 16) [2,38,230].

Hydrofluorination of amino-alcohols of PhCH(OH)CHRNR¹R² type ( where R=H,D,Me; NR¹R²= piperidino; R-Me, NR¹R²=morpholino; R=R¹=R²=Me, R=Ph, NR¹R²=piperidino) under effect of HF/Py system results in formation of a mixture of threo- and erythro-fluoroamines PhCHFCHRNR¹R² , in which the threo-isomer prevails independently on the configuration of the initial aminoalcohol [231]. In hydrofluorination by HF/Py system there is possible rotation around the C-C bond in the carbcation generating followed by hydrogen fluoride attack from the amino-group side to form intermediate carbcations G and D being in dynamic equilibrium.

Preferable formation of the threo-product is caused by the equilibrium shift to the side of the more stable intermediate carbcation D in which steric interactions of substituents are minimal.

The hydroxyl group in the benzyl position is replaced with fluorine by 50-80% under the influence of 70% HF/Py system [232]. Thus, 1-chloro-2-hydroxy-2-phenylethane reacts with HF/Py at room temperature to give 1-chloro-1-fluoro-2-phenylethane.

In case of -isopropylbenzyl alcohol in dependence on the mole ratio of HF and pyridine in HF/Py system the formation of - and -fluorides takes place [233].

The interaction of benzyl ,-aminoalcohol and HF/Py system results in the formation of ,-fluoroamines [234].

Table 16. Production of alkyl fluorides from secondary and tertiary alcohols under the influence of HF/Pr [2].

The steroids containing the OH-group , 14 and 15 groups under the effect of HF/Py complex convert to tertiary fluoro- derivatives 16 only (9-fluoro-derivatives) [235].

When secondary and tertiary OH groups are present the tertiary group is replaced with a fluorine atom [236-238]. Thus, 
3,9-dihydroxy-5--cholest-8(14)-en-15-one under the effect of HF/Py complex in methylene chloride gives 9-fluoro-3- hydroxy-5--cholest-8(14)-en-15-one [236].

-D-Glucopyranoses containing OH or OR groups substitute them with fluorine in position1 under the effect of HF/Py complex already at room temperature for 10 hours [239,240]. An addition of acetone, methene chloride or collidine brings to an increase of total yield of the reaction product.

In case of alcohols containing a cyclopropane ring in a-position the influence of HF/Py/KHF₂/Et₂NH system brings not only to replacement of the hydroxyl group with fluorine but to opening the cyclopropane ring also [241].

Table 17 shows the examples of alcohols which have substituents at the cyclopropane ring.

Interaction of alcohols containing the cyclopropane ring in -position with HF/Py complex or with KHF₂/isopropilamine system results in formation of homo-allyl fluorides with prevalence of the product with E-conformation [242-244].