[75-45-6]  · CHClF2  · Chlorodifluoromethane  · (MW 86.45)

(difluoromethylating reagent, can function as a precursor to difluorocarbene)

Physical Data: bp -40.8 °C.1

Solubility: sol ether, acetone, chloroform.

Form Supplied in: gas.

Preparative Method: prepared by the chlorination of CH2F2 with Cl2;2 by the hydrogenation of CCl2F2 in a Pt-lined tube at high temperature;3 by the halogen-exchange reaction of CHCl3 with HF and SbCl5;4 and by the reaction of HCF2CO2Ag with Cl2.5

Handling, Storage, and Precautions: should be handled in a fume hood.

Reaction with Oxygen Nucleophiles.

Treatment of CHClF2 with alkoxides in the corresponding alcohols gives alkyl difluoromethyl ethers.6 Reaction of CHClF2 with phenols in an aqueous dioxane solution and in the presence of an excess of Sodium Hydroxide produces aryl difluoromethyl ethers (eq 1).7

Reaction with Phosphorus Nucleophiles.

Treatment of the anion of diethyl phosphite with CHClF2 in hexane gives diethyl difluoromethylphosphonate (49%) (eq 2).8 A modification of this route which employed THF as the solvent afforded the difluoromethylphosphonate in higher yield (77%).9

Reaction with Sulfur Nucleophiles.

Reaction of CHClF2 with sulfite in aqueous solution yields the difluoromethanesulfonate (eq 3).10 Treatment of CHClF2 with RSNa gives the difluoromethyl sulfide (eq 4).6,11

Reaction with Carbon Nucleophiles.

Treatment of CHClF2 with phosphonium ylides affords the corresponding 1,1-difluoroalkenes (eq 5).12 Reaction of CHClF2 with the carbanions of an alanine derivative or malonate affords the a-difluoromethylated alanine derivative13 and the a-difluoromethylated malonate,14,15 respectively (eq 6).

Reaction with Nitrogen Nucleophiles.

Treatment of CHClF2 with 2-ethoxycarbonylindole gives the corresponding N-difluoromethyl-2-ethoxycarbonylindole in excellent yield (eq 7).15 When the sodium derivative of carbostyril is treated with CHClF2, however, a mixture of 2-difluoromethoxyquinoline (18-35%), N-difluoromethyl-a-quinolone (10-18%), and two other compounds is obtained (eq 8).15

Difluorocarbene Formation and Reactions.

Difluorocarbene has been generated from CHClF2 and base; it undergoes cycloaddition with alkenes to give the corresponding gem-difluorocyclopropane derivatives (eq 9).16 Tetrafluoroethylene (TFE) is obtained by pyrolysis of CHClF2 at high temperature (eq 10).17

1. Henne, A. L. JACS 1937, 59, 1400.
2. Ruh, R. P.; Davis, R. A. U.S. Pat. 1953, 2 639 300 (CA 1954, 48, 3382f).
3. Benning, A. F.; Young, E. G. U.S. Pat. 1952, 2 615 926 (CA 1953, 47, 8770a).
4. Kwasnik, W. U.S. Pat. 1953, 2 658 927 (CA 1954, 48, 12 788a).
5. Haszeldine, R. N. JCS 1952, 4259.
6. (a) Hine, J.; Porter, J. J. JACS 1957, 79, 5493. (b) Soborovskii, L. Z.; Baina, N. F. JGU 1959, 29, 1113. (c) Hine, J.; Tanabe, K. JACS 1958, 80, 3002. (d) Bagnall, R. D.; Bell, W.; Pearson, K. JFC 1978, 11, 93.
7. (a) Miller, T. G.; Thanassi, J. W. JOC 1960, 25, 2009. (b) Shapiro, E. A.; Eismont, M. Y.; Pereverzeva, Y. O.; Nefedov, A. O.; Strashnenko, A. V.; Kostyrko, I. N.; Roslavtseva, S. A. BAU 1990, 573. (c) Platonov, V. E.; Malyuta, N. G.; Yakobson, G. G. BAU 1972, 2753.
8. (a) Soborovskii, L. Z.; Baina, N. F. JGU 1959, 29, 1115. (b) Bergstrom, D. E.; Shum, P. W. JOC 1988, 53, 3953.
9. Obayashi, M.; Ito, E.; Matsui, K.; Kondo, K. TL 1982, 23, 2323.
10. (a) Farrar. W. V. JCS 1960, 3058. (b) Langlois, B. R. JFC 1990, 46, 407.
11. Moore, G. G. I. JOC 1979, 44, 1708.
12. (a) Wheaton, G. A.; Burton, D. J. TL 1976, 895. (b) Seyferth, D.; Wursthorn, K. R.; Lim, T. F. O.; Sepelak, D. J. JOM 1981, 205, 301. (c) Wheaton, G. A.; Burton, D. J. JOC 1983, 48, 917. (d) Seyferth, D.; Wursthorn, K. R. JOM 1979, 182, 455.
13. Bey, P.; Vevert, J. P. TL 1978, 1215.
14. Tsushima, T.; Kawada, K.; Ishihara, S.; Uchida, N.; Shiratori, O.; Higaki, J.; Hirata, M. T 1988, 44, 5375.
15. Shen, T. Y.; Lucas, S. Sarett, L. H TL 1961, 43.
16. (a) Kamel, M.; Kimpenhaus, W.; Buddrus, J. CB 1976, 109, 2351. (b) Nefedov, O. M.; Ivashenko, A. A. BAU 1968, 1346.
17. Park, J. D.; Benning, A. F.; Downing, F. B.; Laucius, J. E.; McHarness, R. C. Ind. Eng. Chem. 1947, 39, 354.

Donald J. Burton & Weiming Qiu

University of Iowa, Iowa City, IA, USA

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