Sodium chlorodifluoroacetate

Reaction of the cisoid methoxymethylene ketone (36) with decomposing sodium chlorodifluoroacetate yields two epimeric adducts in 42 and 28 % yield, respectively, to which structure (37) has been assigned on the basis of NMR... 

P, lp-Dihydroxy-5fi,6P-difluorom thyleneandrostane Diacetate 17)- A solution of 2.25 g (0.006 mole) of 3, 17/ -dihydroxyandrost-5-ene diacetate, mp 164-166° in diglyme (100 ml), is treated with 7.2 g (0.048 mole) of sodium chlorodifluoroacetate as previously described. The crude product, mp 123-130°, is crystallized from hexane affording unchanged olefin (16 1.64 g) mp 163-165°. The mother liquor is adsorbed from hexane on Florisil (100 g). Elution with hexane-ether (4 1) furnishes an additional 0.3 g of the... 

An older procedure based upon the thermally induced decarboxylation of sodium chlorodifluoroacetate in the presence of triphenylphosphine was used to introduce the difluoromethylene group into a substituted benzo[h]fluoranthene [48] (equation 46)... 

Sodium chlorodifluoroacetate is prepared from chlorodi-fluoroacetic acid (K K Laboratories) as follows To a cooled, stirred solution of 60.7 g. (1.52 moles) of sodium hydroxide in 700 ml. of methanol is slowly added a solution of 198 g. (1.52 moles) of chlorodifluoroacetic acid in 300 ml. of methanol, the temperature being kept below 40°. The methanol is removed under reduced pressure at 40°. The salt, which is pulverized and dried overnight at room temperature at 1 mm., is obtained in essentially quantitative yield. The salt is again dried in the same way immediately before use. 

During the development of this procedure, evolution of carbon dioxide was monitored with a wet-test meter. At the bath temperature given (160°), sodium chlorodifluoroacetate... 

Sodium azide, reaction with l butyl chloroacetate, 46, 47 reaction with diazomum salt from o amino-f> -ni trobiphcny L, 46, 86 Sodium chlorodifluoroacetate, 47, SO reaction with tnphenylphosphme and benzaldehyde, 47, SO Sodium ethoxide, 46, 2S reaction with diethyl succinate, 46,2S Sodium formate as reducing agent in preparation of palladium catalyst, 46, 90... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Sodium chlorodifluoroacetate is prepared in quantitative yield by careful neutralization of 130.5 g. (1.00 mole) of chlorodi-fluoroacetic acid (available from Allied Chemical Corp.) in 300 ml. of ether with 53.0 g. (0.500 mole) of anhydrous sodium carbonate, removal of the solvent and water under reduced pressure, and drying over phosphorus pentoxide in a vacuum desiccator. Studies have shown that the best yield of olefin is obtained when a 100% excess of salt is used. 

Benzaldehyde, condensation, with N-phenylhydroxylamine, 46,127 with chloroform, 48, 27 reaction with triphenylphosphine and sodium chlorodifluoroacetate, 47, 50... 

Sodium chlorodifluoroacetate, reaction with triphenylphosphine and a,a,a-trifluoroacetophenone, 48, 116... 

The procedure illustrates a fairly general method for the preparation of -substituted perfiuoroolefins. The method has been applied to the synthesis of 2-cyclohexyl- (70%), 2-benzyl- (61%), and 2-(/>-fluorophenyl)perfluoropropenes (67%), and it is probably applicable to any a-trifluoromethyl ketone. Olefins containing a perfluoroalkyl group other than trifluoromethyl can be prepared by the same procedure by the substitution of lithium chlorodifluoroacetate for sodium chlorodifluoroacetate.7 Other routes to / -substituted perfiuoroolefins are not general or convenient. Routes to perfiuoroolefins generally yield the a-substi-tuted olefin rather than the /3-substituted olefin. 

The pyrolysis of sodium chlorodifluoroacetate is still a widely used, classical method for generating difluorocarbene, especially with enol and allyl acetates [48, 49, 50, 51] (equation 21) A convenient alternative that avoids the hygroscopic salt uses methyl chlorodifluoroacetate with 2 equivalents of a lithium chlonde-hexa-methylphosphoric triamide complex at 75-80 °C in triglyme [52]. Yields are excellent with electron-rich olefins but are less satisfactory with moderately nucleophilic alkenes (4-5% yields for 2-butenes)... 

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