Ethyl chlorodifluoroacetate

Ethyl chlorodifluoroacetate has been used in a silicon-induced Reformatsky-Claisen reaction of allyl chlorodifluoroacetates in the presence ot zinc as a route to 2,2-difluoro unsaturated acids [( S] (equahon 58) When this methodology is applied to chlorodifluoropropargylic esters, the corresponding allenic esters are formed [SS]... 

A similar Reformatsky reaction, prepared from the cheaper precursor, ethyl chlorodifluoroacetate in dry DMF, has been reported by Lang and Schaub [259] (Scheme 85). Later, Lang demonstrated the preparation of 2,2-difluoro-4-pente-... 

More stable difluoroenol ethers were prepared in four steps from ethyl chlorodifluoroacetate by the Taguchi group (Eq. 127). Lewis acid-mediated additions to aldehydes [330], and to -acyliminium species [331], were described. The choice of Lewis acid was critical for the success of these reactions, particularly in the former case where Lewis acids capable of activity in SET processes were effective, whereas more conventional agents such as trimethylsilyl triflate were not. 

Difluoroacetic acid undergoes reactions typical of a carboxylic acid such as forming an ester when heated with an alcohol and sulfuric acid. Typical esters are methyl difluoroacetate [433-53-4], bp, 85.2°C, and ethyl difluoroacetate [454-31-9], bp, 99.2°C. It can also be photochemicaHy chlorinated to chlorodifluoroacetic acid [76-04-0] or brominated in the presence of iron to bromodifluoroacetic acid [667-27-6] (37,38). 

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-... 

The generation of difluorocarbene has been the subject of intense investigation. Difluorocarbene has been successfully formed from a wide range of fluorinated precursors, including metal salts of chlorodifluoroacetic acid, methyl chlorodifluoroacetate, ethyl chlorodi-fluoroacetate, difluorodiiodomethane, " chlorodifluoromethane." " difiuorotris(trifluoro-methyl)-A -phosphane hexafluoropropylene oxide,tetrafluoroethylene... 

ICOBu-0 - cell (w Molhyllllhium). lym-Dinuoroletrachloroacetone (K.OBu-r) — CFCI. Ethyl trichloroacetale (NaOCHi) -< CX lj. Lithium ethoxide, generation of 2,2-diphenyl-cyclopropylidene. Phenyl(bromodichloro)mercury (80°) —> CBrj. Phenyl(trichloromethyl)-mercury (47 hrs. at 80° or Nal at 25°) -> CCli. Sodium chlorodifluoroacetate (heat) - CFs. Sodium trichloroacetate (heat) -> CCIj. 

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