394-98-9

Upstream product

• 378-99-4 α,α,β-trichloro-β,β-difluoroethylbenzene 
• 1514-87-0 metyhyl chlorodifluoroacetate 
• 384-67-8 2-chloro-2,2-difluoroacetophenone 
• 309-10-4 1,1,1-trifluoro-2,2-dichloro-2-phenylethane 
• 384-65-6 1-chloro-2,2,2-trifluoroethylbenzene 
• 124-41-4 sodium methylate 
• 434-44-6 1,2-dichloro-1-phenyl-2,2-difluoroethane 
• 78844-54-9 α-Chlor-α-Deutero-β,β,β-trifluoraethylbenzol 
• 75-45-6 Chlorodifluoromethane 
• 98-07-7 Benzotrichlorid 
• 60-29-7 diethyl ether 
• 591-50-4 iodobenzene 
• 75-88-7 1,1,1-trifluoro-2-chloroethane 
• 151-67-7 1,1,1-trifluoro-2-bromo-2-chloroethane 

Downstream Products

• 40193-71-3 (1,2-Dibromo-1-chloro-2,2-difluoro-ethyl)-benzene 
• 384-65-6 1-chloro-2,2,2-trifluoroethylbenzene 
• 78844-54-9 α-Chlor-α-Deutero-β,β,β-trifluoraethylbenzol 
• 58852-20-3 α-Chlor-α-Tritio-β,β,β-trifluoraethylbenzol 

Relevant academic research and scientific papers

Reaction of Halothane with sec-butyllithium in the presence of zinc halides - One-pot preparation of chlorodifluorovinylzinc reagent and its derivatization to α-chloro-β,β-difluorostyrene

Halothane, 2-bromo-2-chloro-1,1,1-trifluoroethane, reacts with sec -butyllithium in the presence of zinc halides to afford a chlorodifluorovinylzinc reagent. This zinc reagent reacts with aryl halides in the presence of a palladium catalyst to give chlorodifluorostyrene derivatives in moderate to good yields.

Cross coupling in water: Suzuki-Miyaura vinylation and difluorovinylation of arylboronic acids

A general and efficient protocol for the Suzuki-Miyaura coupling of aryl boronic acids with vinylmesylate or difluorovinylmesylate or Cl 2CCF2 in water or water/n-butanol is reported, utilizing Na2PdCl4 (1 mol%) and a highly water-soluble fluorenylphosphine (CataCXium F sulf).

An efficient dehyrohalogenation method for the synthesis of α,β,β-trifluorostyrenes, α-chloro-β,β- difluorostyrenes and E-1-arylperfluoroalkenes

Dehydrofluorination of 1-aryl-1,2,2,2-tetrafluoroethanes (ArCHFCF 3) and 1-aryl-1-chloro-2,2,2-trifluoroethane (ArCHClCF3) using lithiumhexamethyldisilazide (LHMDS) in tetrahydrofuran (THF) at room temperature produced 1,2,2-trifluorostyrene and 1-chloro-2,2-difluorostyrene, respectively, in very good isolated yields. Dehydrofluorination of 1,2,2,3,3,3-hexafluoro-1-phenyl-propane (PhCHFCF2CF3) and 1,2,2,3,3,4,4,4-octafluoro-1-phenyl-butane (PhCHFCF2CF 2CF3) using LHMDS produced the corresponding substituted olefins (1-phenyl-1,2,3,3,3-pentafluoroprop-1-ene and 1-phenyl-1,2,3,3,4,4,4- pentafluorobut-1-ene) in good yield and high E-selectivity. Dehydrofluorination of 1-chloro-1-phenyl-2,2,3,3,3-pentafluoropropane (PhCHClCF2CF 3) and 1-chloro-1-phenyl-2,2,3,3,4,4,4-heptafluorobutane (PhCHClCF2CF2CF3) produced a mixture of the corresponding E and Z olefins (PhCClCFCF3 and PhCClCFCF 2CF3) in good yield.

Room temperature preparation of α-chloro-β,β- difluoroethenylzinc reagent (CF2CClZnCl) by the metallation of HCFC-133a (CF3CH2Cl) and a high yield one-pot synthesis of α-chloro-β,β-difluorostyrenes

α-Chloro-β,β-difluorovinylzinc reagent [CF 2CClZnCl] was generated in 91% yield by the metallation of a THF solution of commercially available HCFC-133a (CF3CH2Cl) and zinc chloride at 15-20 °C using LDA as base. The corresponding reaction with Halothane (CF3CHClBr) produced a poor yield of CF 2CClZnCl. The palladium catalyzed coupling reaction of the CF 2CClZnCl with aryl iodides under mild reaction conditions produced α-chloro-β,β-difluorostyrenes in 64-90% isolated yields. The stability of the intermediate CF2CClLi and the nature of the zinc reagents are discussed.

The room temperature preparation of the 1-chloro-2,2-difluorovinylzinc reagent from HCFC-133a (CF3CH2Cl). The first ambient, high yield, one-flask preparation of α-chloro-β,β-difluorostyrenes

The reaction of LDA (2.0 equiv.) with a THF solution of ZnCl2 (1.0 equiv.) and HCFC-133a (CF3CH2Cl) (1.0 equiv.) at 15-20°C gives a 91% yield of [F2C=CClZnCl]. Addition of ArI and Pd(PPh3)4 at rt to 65°C gives 65-85% isolated yields of ArCCl=CF2. This one-flask procedure provides the first room temperature generation of the 1-chloro-2,2-difluorovinylzinc reagent and the first high yield preparation of α-chloro-β,β-difluorostyrenes from a cheap, readily available industrial precursor.

Use of kinetic isotope effects in mechanism studies. Isotope effects and element effects associated with Hydron-Transfer steps during alkoxide-promoted dehydrohalogenations

The Arrhenius behavior of the primary kinetic isotope effect, (k(H)/k(D))(Obs) and (k(H)/k(T))(Obs), associated with the methanolic sodium methoxide-promoted dehydrohalogenations of m-ClC6H4C(i)HClCH2Cl (I), m-CF3C6H4C(i)-HClCH2Cl (II) and p-CF3C6H4C(i)HClCH2F (III) has been used to calculate the internal-return parameters, a = k(-1)/K(Elim)(X), in a two-step mechanism featuring a hydrogen-bonded carbanion. This carbanion partitions between returning the hydron to carbon, k(-1), and the loss of halide, K(Elm)(X). Isotope effects at 25°C for I, (k(H)/k(D))(Obs) = 3.40 and (k(H)/ k(T))(Obs) = 6.20, and II, (k(H)/k(D))(Obs) = 3.49 and (k(H)/k(T))(Obs) = 6.55, result in similar values for a: a(H) = 0.59, a(D) = 0.13-0.14 and a(T) = 0.07. Smaller values of (k(H)/k(D))(Obs) = 2.19 and (k(H)/k(T))(Obs) = 3.56 for III are due to more internal return [a(H) = 1.9, a(D) = 0.50, and a(T) = 0.28] associated with the dehydrofluorination reaction. Calculation of k1 ( k(Obs) [a + 1]) results in similar isotope effects for hydron transfer in these reactions: k1(H)/k1(D) = 4.74 and k1(H)/K1(T) = 9.20; II, k1(H)/k1(D) = 4.91 and k1(H)/k1(T) = 9.75; III, k1(H)/k1(D) = 4.75 and k1(H)/k1(T) = 9.17. Reactions of m-ClC6H4C(i)HBrCH2Br and m-ClC6H4C(i)HClCH2Br have very small amounts of internal return, a(H) = 0.05 and a(D) = 0.01, and (k(H)/k(D))(Obs) = 4.95 results in k1(H)/k1(D) = 5.11 The measured isotope effects are therefore due to differences in the amount of internal return and not in the symmetry of transition state structures for the hydron transfer, and the element effect, (k(HBr)/ k(HCl)) = 29, for m-ClC6H4CHClCH2X is mainly due to the hydron-transfer step, k1(HBr)/k1(HCl) = 19, and not the breaking of the C-X bend. The kinetic solvent isotope effects, k(MeOD)/k(MeOH) ~ 2.5, are consistent with three methanols of solvation lost prior to the hydron-transfer step. The energetics associated with desolvation of methoxide ion are part of the measured reaction energetics of these systems.

Use of Kinetic Isotope Effects in Mechanism Studies. 4. Chlorine Isotope Effects Associated with Alkoxide-Promoted Dehydrochlorination Reactions

The method of measuring k35/k37 for the alkoxide-promoted deprotiochlorination and dedeuteriochlorination reactions has been applied to C6H5CiH(CH3)CH2Cl (I-Cl), C6H5CiHClCH2Cl (V), and C6H5CiHClCF2Cl(III).For reactions occuring with ethanolic sodium ethoxide the following values for k35/k37 have been measured: I-Cl-h, 1.00590 + 0.00013, and I-Cl-d, 1.00507 +/- 0.00036 at 75 deg C; V-h, 1.00908 +/- 0.00008, and V-d, 1.00734 +/- 0.00012 at 24 deg C; III-h, 1.01229 +/- 0.00047, and III-d, 1.01003 +/- 0.00024 at 0 deg C.Methanolic sodium methoxide promoted eliminations gave similar results for V and III: V-h, 1.00978 +/- 0.00020, and V-d, 1.00776 +/- 0.00020 at 21 deg C; III-h, 1.01255 +/- 0.00048, and III-d, 1.01025 +/- 0.00043 at 20 deg C.The results for I-Cl are most consistent with an E2 mechanism, while the results for III and V suggest a multistep reaction sequence.The Arrhenius behavior of ethoxide-promoted dehydrochlorination of V-h gives a good linear correlation between -10 and 50 deg C, with an EaH = 21.26 +/- 0.05 kcal/mol and ln AH = 29.29 +/- 0.09.Rate constants measured for 55, 60, 65, and 70 deg C show increasing negative deviation from the slope.Similar behavior was not observed for V-d which resulted in EaD = 21.57 +/- 0.28 and ln AD = 28.37 +/- 0.28 when rate constants over a 50 deg C range (20 - 70 deg C) were used.The ΔEaD-H = 0.31 and AH/AD = 2.5 for an observed kH/kD = 4.24 at 25 deg C were similar for results obtained for III.The possibility that the high values of k35/k37 for both III and V could result from a chlorine isotope effect associated with the proton transfer step of an E1cB mechanism is discussed.

Proton-Transfer Reactions. 4. Near-Unity Kinetic Isotope Effects for Hydron Exchange and Dehydrofluorination Reactions

Rates and isotope effects are reported for benzylic hydron exchange and dehydrofluorination reactions of C6H5CiHClCF3 (I) and C6H5CiH(CF3)2 (II) in alcoholic sodium alkoxide solutions.Reactions of I were studied in ethanol and isotop

Proton-Transfer Reactions. 1. Partitioning of Carbanion Intermediates Generated by Reactions of Alkenes with Alkoxide Ions in Alcohol

Nucleophilic reactions with sodium alkoxide in alcohol have been studied with various gem-difluoroalkenes of general structure C6H5CR=CF2.Rates and Arrhenius paramaters 3 (M -1 s-1) at -50 deg C, ΔH* (kcal mol-1), and ΔS*, (eu)> are respectively: R = -CF3 (II), 105, 9, and -23; -CF2Cl (III), 135, 10 and -19; -CF2CF3 (IV), 40.6, 9, and -23; -CF2H (V), 3.63, 11, and -19.Reactions proceed via carbanion intermediates, and the products from reaction with ca. 0.3 N sodium ethoxide in ethanol are: II, 85percent vinyl ether and 15percent saturated ether; III, 100percent allylic ether; IV; 74percent vinyl ether, 22percent allylic ether, and 4percent saturated ether; V, >98percent allylic ether.The observed product distribution suggest the following order of leaving group ability for fluoride in different environments: -CF2H >> -CF2OR > -CF2CF3 >> -CF3.Solvent protonation of the carbanion is apparently slower than fluoride ion ejection from all groups studied other than trifluoromethyl.Product isotope effects (PIE), kH/kD, for the protonation of the carbanion generated from II by reaction in ethanol are 1.50 (-78 deg C) and 1.86 (20 deg C) and by reaction in methanol are 1.22 (-78 deg C).

Proton-Transfer Reactions. 2. Effects of Internal Return on Reactivity Difference between Alkoxide-Promoted Eliminations in tert-Butyl alcohol and Ethyl Alcohol

Kinetics of alkoxide-promoted dehydrofluorination reactions are reported for the series C6H5CH2CH2F (I), C6H5CH2CHF2 (II), C6H5CH2CF3 (III), and C6H5CH2CF2CF3 (V).Rates and activation parameters 3 (M-1 s-1)(50 deg C), ΔH* (kcal mol-1), and ΔS*, (eu)> are respectively: (a) using potassium tert-butoxide in tert-butyl alcohol, I (1.88 * 10-4, 19.1, -16.8), II (1.18 * 10-3, 20.3, -9.3), III (2.15 * 10-3, 22.1, -2.4), V (3.93 * 10-2, 16.9, -12.7); and (b) using sodium ethoxide in ethanol, I (1.32 * 10-6, 25.6, -6.5), II (5.28 * 10-7, 29.7, 3.0), III (3.45 * 10-7, 32.6, 12.5), V (5.41 * 10-5, 27.7, 7.6).The variation in tert-butoxide:ethoxide ratios of 140 (I), 2200 (II), 6200 (III), and 730 (V) are discussed in terms of a two-step mechanism with varying amounts of internal return for II, III, and V.Differences in reactivity for groups attached to the benzylic carbon (-CF3, -CF2Cl, -CHF2, -CF2CF3) and variation of ΔS* values for these reactions are also discussed in terms of a two-step mechanism.