Alpha-(trifluoromethyl)amine derivatives via nucleophilic trifluoromethylation of nitrones

(Trifluoromethyl)trimethylsilane (TMSCF(3)) reacts with nitrones to afford alpha-(trifluoromethyl)hydroxylamines protected as O-trimethylsilyl ethers. Potassium t-butoxide initiates the nucleophilic trifluoromethylation. The reaction works best with alpha,N-diaryl nitrones, and the conditions are compatible with a range of substituents on the aryl groups. Acidic deprotection of the nitrone/TMSCF(3) adducts generates alpha-(trifluoromethyl)hydroxylamines. Catalytic hydrogenation of the adducts produces alpha-(trifluoromethyl)amines. Nitrone/TMSCF(3) adducts with strong electron-withdrawing groups on the alpha-aryl ring or heterocyclic alpha-aryl groups undergo an elimination/addition sequence to generate alpha,alpha-bis(trifluoromethyl)amines. Nitrones with alkyl groups bound directly to the 1,3-dipolar moiety fail to react with TMSCF(3), but trifluoromethylation of beta,gamma-unsaturated nitrones followed by reduction of the double bond can circumvent this limitation.     

Synthesis of aromatic trifluoromethyl compounds by ring expansion of cyclodienes

Chlorotrifluoromethyl-1-diazirine was used for a source of chlorotrifluoromethyl carbene. The carbene added to cyclic dienes to give trifluoromethylated six-membered aromatic compounds. Thus, pyrrole gave 3-(trifluoromethyl)pyridine and cyclopentadiene gave benzotrifluoride.In the course of out research to develop a new synthetic method for aromatic trifluoromethyl compounds [1], we planned to use the reaction of chlorotrifluoromethyl carbene (1) with a five-membered cyclic diene. The reaction of pyrrole with dichlorocarbene was reported to give 3-chloropyridine [2]. Therefore, we expected that the similar type of reaction of 1 with a five-membered cyclic diene would provide a new method for the syntheses of aromatic trifluoromethyl compounds. We chose chlorotrifluoromethyl-1-diazirine (2) [3] as the precursor of 1.First, we examined the reaction of 2 with cyclohexene to learn the reactivity of 1. Heating the solution of 2 in cyclohexene at 120° for 3 h gave two adducts (3 and 4). Both products were separated by the preparative g.l.c. using a DEGS column of 7 m at 60°C. 3: 36%; m/e 198 (M⁺); ¹H-NMR δ(CDCl₃) 0.88?2.60 (m); ¹⁹F-NMR δ [4] 10.2. 4: 10% m/e 198; ¹H-NMR δ(CDCl₃) 0.80?2.60; ¹⁹F-NMR δ ?1.2. Compound 3 reacted with silver trifluoroacetate to give 2-(trifluoromethyl)cyclohepten-3-yl trifluoroacetate, while 4 did not. This result established the Stereochemistry of both products as shown in Chart 1. This reaction showed that 2 was a good precursor of 1 and that 1 had a high reactivity to a double bond.To utilized this reaction for the synthesis of an aromatic trifluoromethyl compound, thermolysis of 2 with five-membered cyclic dienes was investigated. A solution of 2 (230 mg) in pyrrole (500 mg) was sealed in a Pyrex tube under vacuum and heated at 120°C for 2 h. The reaction mixture was purified by a trap-to-trap distillation. Analysis of the distillate by g.l.c. showed that 3-(trifluoromethyl)pyridine (5) was obtained in 35% yield based on 2. The g.l.c-mass spectrum and ¹⁹F-NMR of 5 were identical with those of the authentic sample [5]. Similar thermolysis and work-up of a solution of 2 (160 mg) in cyclopentadiene (550 mg) at 140°C for 3 h gave benzotrifluoride in 23% yield. All the results are summarized in Chart 1.The characteristic point of this procedure is that a trifluoromethyl group was introduced to a five membered ring with one carbon atom under ring expansion. Yields shown above were not optimized and this method can be used for synthesis of some aromatic trifluoromethyl compounds, which are difficult to synthesize by the usual methods.     

Highly soluble and optically transparent poly (ether imide)s based on 2,6‐ or 2,7‐bis(3,4‐dicarboxyphenoxy)naphthalene dianhydride and aromatic bis(ether amine)s bearing trifluoromethyl groups

Two series of novel fluorinated poly(ether imide)s (coded IIIA and IIIB ) were prepared from 2,6‐bis(3,4‐dicarboxyphenoxy)naphthalene dianhydride and 2,7‐bis(3,4‐dicarboxyphenoxy)naphthalene dianhydride, respectively, with various trifluoromethyl‐substituted aromatic bis(ether amine)s by a standard two‐step process with thermal or chemical imidization of the poly(amic acid) precursors. These fluorinated poly(ether imide)s showed good solubility in many organic solvents and could be solution‐cast into transparent, flexible, and tough films. These films were nearly colorless, with an ultraviolet–visible absorption edge of 364–386 nm. They also showed good thermal stability with glass‐transition temperatures of 221–298 °C, 10% weight loss temperatures in excess of 489 °C, and char yields at 800 °C in nitrogen greater than 50%. The 2,7‐substituted IIIB series also showed better solubility and higher transparency than the isomeric 2,6‐substituted IIIA series. In comparison with nonfluorinated poly (ether imide)s, the fluorinated IIIA and IIIB series showed better solubility, higher transparency, and lower dielectric constants and water absorption. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5909–5922, 2006     

Photoisomerization of bis(trifluoromethyl)thiophenes

The photolysis of 2,3-bis(trifluoromethyl)thiophene gave an equilibrium mixture of 2,3- and 3,4-bis(trifluoromethyl)Dewar thiophenes, while that of 2,5-bis(trifluoromethyl)thiophene gave 2,4-bis(trifluoromethyl)-thiophene, which seemed to be formed through an intermediate other than the Dewar form.     

Highly regioselective ring opening of epoxides and aziridines using (bromodimethyl)sulfonium bromide

Epoxides and aziridines undergo ring opening efficiently with (bromodimethyl)sulfonium bromide at room temperature to form the corresponding β-bromohydrins and β-bromoamines, respectively. The conversions are highly regioselective and afford the products in excellent yields within a short period of time.     

Biginelli reaction for synthesis of novel trifluoromethyl derivatives of bis(tetrahydropyrimidinone)benzenes

A facile one-pot three-component condensation of terephthalic aldehyde with urea and fluorinated 1,3-dicarbonyl derivatives is developed using catalytic quantities of chlorotrimethylsilane at ambient temperature. As a consequence, efficient synthesis of novel trifluoromethyl derivatives of bis(tetrahydropyrimidinone)benzenes is observed within short time periods. The procedure is shown to be equally efficient when urea is replaced with thiourea or guanidine.     

Infrared photochemistry of bis(trifluoromethyl) peroxide

Bis(trifluoromethyl) peroxide is readily dissociated by multiple infrared photon excitation at CO₂ laser wavelengths. The primary dissociation product is CF₃O; approximately 85% of the nascent radicals are further dissociated in the laser field to form CF₂O and F. The F atoms then react with the remaining CF₃O to produce CF₃OF. The formation of CF₃OF is strongly inhibited by addition of HI, which reacts preferentially with the F atoms.     

New regioselective synthesis of metalinked aromatic polyketones from metasubstituted bis(arylsilane)s and aromatic dicarboxylic acid chlorides

A new regioselective synthesis of metalinked aromatic polyketones was achieved for the first time. New metaconnected aromatic polyketones with inherent viscosities of up to 0.49 dL/g were regioselectively synthesized by the solution polycondensation of metasubstituted bis(arylsilane)s with aromatic dicarboxylic acid chlorides in the presence of aluminum chloride in 1,2‐dichloroethane along with the elimination of chlorotrimethylsilane. The polycondensation proceeded through aromatic electrophilic ipso‐substitution. The metalinked aromatic polyketones had considerably lower glass‐transition temperatures and 10% weight‐loss temperatures than those of their counterpart paracatenated aromatic polyketones. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1428–1434, 2003     

First example of regioselective nucleophilic 1,6-addition of trimethyl(trifluoromethyl)silane to 4H-chromene derivatives

Condensation of 2-trifluoromethylchromone with diethyl malonate, ethyl cyanoacetate, and Meldrum’s acid gave the corresponding methylidene derivatives of 2-trifluoromethyl-4H-chromene. Nucleophilic 1,6-addition of an excess of Me₃SiCF₃ in the presence of Me₄NF to those obtained from the former two compounds afforded 4-substituted 2,2-bis(trifluoromethyl)-2H-chromenes. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1628–1630, September, 2006.     

Isotope effects on miscibility of 1-alkyl-3-methylimidazolium bis(trifluoromethyl)sulfonyl imides with aromatic hydrocarbons

The liquid–liquid miscibility temperatures as a function of composition and deuterium substitution have been experimentally determined for the binary mixtures of 1-decyl-3-methylimidazolium bis(trifluoromethyl)sulfonyl imide, [C₁₀MIM][NTf₂], and 1-dodecyl-3-methylimidazolium bis(trifluoromethyl)sulfonyl imide, [C₁₂MIM][NTf₂] with benzene and toluene and their deuterated forms. All systems exhibit upper critical solution temperatures (UCSTs) and better miscibility for ionic liquids with longer alkyl chain. The interchange of benzene for toluene results in worse miscibility for [C₁₀MIM][NTf₂] and better for [C₁₂MIM][NTf₂]. Deuteration of the aromatics leads to better miscibility in each case. The sign of the isotope effect is in agreement with expectations and its value seems to be seriously affected by the neighborhood of the hypercritical state.     

Highly regioselective hydroselenation and double-bond isomerization of terminal alkynes with benzeneselenol catalyzed by bis(triphenylphosphine)palladium(II) dichloride

Bis(triphenylphosphine)palladium(II) dichloride (PdCl₂(PPh₃)₂) catalyzes regioselective addition of benzeneselenol to terminal alkynes and the subsequent double-bond isomerization to afford the corresponding internal alkenyl selenides in good yields.     

Reactions of tetrakis(trifluoromethyl) diphosphine and bis(trifluoromethyl) phosphine with ruthenium carbonyl clusters; X-ray structure of tetraruthenium carbonyl cluster derivatives

Reaction of [Ru₃(CO)₁₂ with (CF₃)₂P---P(CF₃)₂ in p-xylene at 140°C yielded the compounds [Ru₄(CO)₁₃{μ-P(CF₃)₂}₂] (1), [Ru₄(CO)₁₄{μ-P(CF₃)₂}₂] (2) and [Ru₄(CO)₁₁{μ-P(CF₃)₂}₄] (3). Reaction with [(μ-H)₄Ru₄(CO)₁₂] under similar conditions yielded [(μ-H)₃Ru₄(CO)₁₂{μ-P(CF₃)₂}] (4). All four compounds have been characterised by X-ray crystallography. The fluxional behaviour of the hydrides in 4 has also been studied by variable-temperature NMR spectroscopy. Compounds 1, 2 and 4 were also obtained from the reactions of Ru₃(CO)₁₂ with (CF₃)₂PH in dichloromethane at 80°C.     

1-(三氟甲基)-1,2-苯碘酰-3(1H)-酮在芳杂环上三氟甲基化的应用研究

以1-(三氟甲基)-1,2-苯碘酰-3(1H)-酮为三氟甲基源,并以2-氨基-5-溴吡啶为三氟甲基化底物,采用响应面分析法对合成工艺进行了分析优化,确定了最佳反应条件为:反应时间4 h,催化剂用量0.16 eq,反应温度50℃.经过3次验证实验,其平均收率为87％.最后继续合成了多个三氟甲基杂环芳香胺,且化合物结构经1...     

Highly regioselective synthesis of trifluoromethyl derivatives of pyrazolo[1,5-a]pyrimidines bearing fused cycloalkane rings using (2-ethoxycycloalkenyl)-2,2,2-trifluoroethanones

8-Trifluoromethyl-6,7-dihydro-5H-1,4,8a-triaza-s-indacene and 9-trifluoromethyl-5,6,7,8-tetrahydropyrazolo[5,1-b]quinazolines were efficiently generated by condensation of 5(3)-aminopyrazoles with (2-ethoxycycloalkenyl)-2,2,2-trifluoroethanones and isolated in excellent yields. The regiochemistry of the prepared compounds was established by ¹H, ¹³C and ¹⁹F NMR spectroscopy and X-ray diffraction analysis.     

Chemistry of trifluoromethyl compounds : I. NMR evidence for bis(trifluoromethyl)zinc and methyl(trifluoromethyl)zinc

Bis(trifluoromethyl)zinc and methyl(trifluoromethyl)zinc have been identified by ¹⁹F and ^1H NMR methods. The compounds were formed in the following reactions: (1) dimethylzinc and bis(trifluoromethyl)mercury and (2) dimethylzinc and bis(trifluoromethyl)cadmium.     

Highly regioselective ring opening of epoxides with alcohols catalyzed by organotin phosphate condensates

Organotin phosphate condensates proved to catalyze the ring opening reaction of epoxides with alcohols in a highly regioselective manner.     

Synthesis of the first chiral bidendate bis(trifluoromethyl)phosphane ligand through stabilization of the bis(trifluoromethyl)phosphanide anion in the presence of acetone

Lewis acid/Lewis base adduct formation of the P(CF3)2- ion and acetone leads to a reduced negative hyperconjugation and, therefore, limits the C--F bond activation. The resulting increased thermal stability of the P(CF3)2- ion in the presence of acetone allows selective substitutions and enables the synthesis of the first example of a chiral, bidentate bis(trifluoromethyl)phosphane ligand: a DIOP derivative, [(2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene)]bis(diphenylphosphane), in which the phenyl groups at the phosphorus atoms are replaced by strong electron-withdrawing trifluoromethyl groups. The resulting high electron-acceptor strength of the synthesized bidentate (CF3)2P ligand is demonstrated by a structural and vibrational study of the corresponding tetracarbonyl-molybdenum complex. The stabilization of the P(CF3)2- ion in the presence of acetone is based on the formation of a dynamic Lewis acid/Lewis base couple, (CF3)2PC(CH3)2O-. Although there is no spectroscopic evidence for the formation of the formulated alcoholate ion, the intermediate formation of (CF3)2PC(CH3)2O- could be proved through the reaction with (CF3)2PP(CF3)2, which yields the novel phosphane-phosphinite ligand (CF3)2PC(CH3)2OP(CF3)2. This ligand readily forms square-planar Pt(II) complexes upon treatment with solid PtCl2.