Primary Alkyl Fluorides

The results of the reduction of fluorocholestane (2) under various conditions (solvent, metal, crown ether, H" ) are shown in Table II. Alkyl fluorides (primary, secondary, tertiary) were reduced under standard conditions [K/DC-18-C-6 (2 mol eq.)/toluene at ambient temperature], and the results are shown in Table III. 

The order of reactivity of the hydrogen halides parallels their acidity HI > HBr > HCl >> HF Hydrogen iodide is used infrequently however and the reaction of alco hols with hydrogen fluoride is not a useful method for the preparation of alkyl fluorides Among the various classes of alcohols tertiary alcohols are observed to be the most reactive and primary alcohols the least reactive... 

Benzyl and alkyl tnalkylsilyl ethers undergo clean fluonnation to give good yields of benzyl and alkyl fluorides, respectively, when reacted with a combination of d quaternary ammonium fluoride and methanesulfonyl orp- toluenesulfonyl fluoride. The reactions are applicable strictly to a primary carbon-oxygen bond, secondary and tertiary alkyl silyl ethers remain intact or, under forcing conditions, aie dehydrated to olefins [29] (equation 22)... 

Lower aliphatic primary alcohols including octanol, halogeno alcohols, and benzylic alcohols yield only alkyl fluorides [81, 82 The reaction of higher primary alcohols gives a mixture of fluorides and alkyl 2,3,3,3-tetrafluoropropionates [S3] and 2-nitro alcohols, alcohols branched at C-2 [82, 84 and unsaturated alcohols [55] give 2,3,3,3-tetrafluoropropionates exclusively... 

In some cases it is possible to differentiate between the various alkyl substituents. Primary, secondary and tertiary nitrates and nitrites all show clearly different infrared absorptions. The spectra of acid fluorides can be used to differentiate chain-end groups from pendant acid groups. Furthermore, the loss of all -OH species upon sulfur tetrafluoride exposure allows the reliable estimation of ketones, esters and lactones without the complication of hydrogen-bonding induced shifts in the spectra. Preliminary results from the use of these reactions to characterize y-ray oxidized polyethylene and polypropylene are used to illustrate the scope of the methods. 

The typical chemical shift for primary n-alkyl fluorides is -219, but the values for primary alkyl fluorides vary between -212 for ethyl fluoride and -226 for 2-ethyl-l-fluorobutane (Scheme 3.1). As mentioned above, alkyl branching leads to shielding of fluorine nuclei. 

H and 13C NMR Data. The examples in Scheme 3.3 provide insight into expected proton and carbon chemical shift and coupling constant data for primary alkyl fluorides. It can be seen that the influence on both proton and carbon chemical shifts diminishes rapidly as one moves away from the site of fluorine substitution. 

Secondary alkyl fluorides exhibit a downfield (deshielding) shift of about +35 ppm from their primary analogues, their fluorines typically absorbing at about -183 ppm (Scheme 3.4), and such fluorines will also experience the usual considerable shielding as a result of branching. 

In contrast to the primary alcohols, tertiary alcohols eliminate water smoothly at 0°C in the presence of a 2-10 molar excess of hydrogen fluoride followed by polymerization.259 Reduced polymerization and satisfying yields of tertiary alkyl fluorides are achieved only at low temperatures (— 50 C). The reactivity of secondary aliphatic alcohols is thus interpreted to be between the other two types. High yields of alkyl fluorides are difficult to obtain because of the competing reactions and the effect of temperature on the equilibrium. 

Alkyl fluorides have been generated from the reaction of carboxylic acids with one equivalent of xenon difluoride in dichloromethane or chloroform solution. The process has been named fluorodecarboxylation", the fluorine analog of the Hunsdieckerand Kochi reaction.8384 Both primary and tertiary acids react very well, but secondary acids react less readily. A possible scheme involves a free-radical mechanism including an unstable fluoroxenon ester of an appropriate acid.84... 

Fluorodecarboxylation.1 Reaction of alkanoic acids with XeF2 in CH2C12 can result in alkyl fluorides by replacement of the COOH group by F. Yields are highest with primary, tertiary, and benzylic acids. Aryl or vinylic acids do not undergo this reaction. 

Herrera, R. P. Guijarro, A. Yus, M. Primary alkyl fluorides as regioselective alkylating reagents of lithium arene dianions. Easy prediction of regioselectivity by MO calculations on the dianion. Tetrahedron Lett. 2003, 44, 1313-1316. 

Herrera, R. P. Guijarro, A. Yus, M. Primary alkyl fluorides as regioselective alkylating... 

Grignard reagents may be made from primary, secondary, and tertiary alkyl halides, as well as from vinyl and aryl halides. Alkyl iodides are the most reactive halides, followed by bromides and chlorides. Alkyl fluorides generally do not react. 

The preparation of fluorinated carbohydrates via nucleophilic displacement of the. sulfonate group of the corresponding sulfonates by fluoride is a well-known rcaction " however, potassium fluoride, which was used to prepare the first alkyl fluoride type of sugar derivative, has been progressively replaced by the alkylamine fluorides (.see Section 1.1.4.2.1.2.). The substitution of relatively unhindered primary mesylates or tosylates in cxocyclic positions of carbo-... 

Fluorinatlon. Primary and secondary alkyl halides and tosylates are converted into alkyl fluorides by reaction with 1 in THF. Alkenes are formed as by-products. 

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