Trifluoroacetic acid sulfoxide

Esters derived from the primary alcohols are the most stable and those derived from the tertiary alcohols are the least stable. The decomposition temperature is lower in polar solvents, eg, dimethyl sulfoxide (DMSO), with decomposition occurring at 20°C for esters derived from the tertiary alcohols (38). Esters of benzyl xanthic acid yield stilbenes on heating, and those from neopentyl alcohols thermally rearrange to the corresponding dithiol esters (39,40). The dialkyl xanthate esters catalytically rearrange to the dithiol esters with conventional Lewis acids or trifluoroacetic acid (41,42). The esters are also catalytically rearranged to the dithiolesters by pyridine Ai-oxide catalysts (43) ... 

Androst-4-ene-3,17-dione. Testosterone (0.58 g, 2 mmoles) is dissolved in a solution prepared from 3 ml of benzene, 3 ml of dimethyl sulfoxide, 0.16 ml (2 mmoles) of pyridine and 0.08 ml (1 mmole) of trifluoroacetic acid. After addition of 1.24 g (6 mmoles) of dicyclohexylcarbodiimide, the sealed reaction flask is kept overnight at room temperature. Ether (50 ml) is added followed by a solution of 0.54 g (6 mmoles) of oxalic acid in 5 ml of methanol. After gas evolution has ceased ( 30 min) 50 ml of water is added and the insoluble dicyclohexylurea is removed by filtration. The organic phase is then extracted twice with 5 % sodium bicarbonate and once with water, dried over sodium sulfate and evaporated to a crystalline residue (0.80 g) which still contains a little dicyclohexylurea. Direct crystallization from 5 ml of ethanol gives androst-4-ene-3,17-dione (0.53 g, 92%) in two crops, mp 169-170°. 

The cleavage of this group proceeds by initial reduction of the sulfoxide, which then makes the resulting methylthiobenzyl ether labile to trifluoroacetic acid. Thus, any method used to reduce a sulfoxide could be used to activate this group for deprotection. 

The sulfoxide 5 on treatment with trifluoroacetic acid in dichloromethane at 20 °C for three hours undergoes a Pummerer reaction (see Houben-Weyl, Vol.Ell, pll89ff) to give the thiazepinone 6 in 79% yield. No further details were reported.48... 

The formation of stable disulfonium dications from certain bis-sulfides provided an impetus for re-evaluating the mechanisms of some old reactions. The isomerization of sulfoxide 124, using trifluoroacetic acid, involved an acid-catalyzed migration of an oxygen atom from a sulfoxide to sulfide (see Equation 36). This was one of the first examples in which an intermediate formation of an S-S dication was proposed. Recently, such a dication 125 was detected in a non-nucleophilic medium such as sulfuric acid <1995HAC145>. 

Acid-catalyzed migration of an oxygen atom from a sulfoxide to sulfide is one of the first examples where an intermediate formation of a S-S dication was proposed.26 Recently, such intermediates were observed by physical methods. Kinetic studies suggested that an intramolecularly formed S-S dication 54 was involved in isomerization of sulfoxide 53 to 55 under influence of trifluoroacetic acid (Scheme 18).82... 

Reaction of S-oxide of 1,4-dimethylthiobenzene 56 with trifluoroacetic acid provides another example of an oxygen atom migration that proceeds through a dication. The dication is in rapid equilibrium with the protonated sulfoxide 57 (Scheme 19).83... 

Kim and Okamoto carried out studies on a tautomeric equilibrium between a hydrazono and azo derivative, 46 and 47 respectively, by means of NMR spectroscopy (Scheme 3) <1994JHC233>. The 13C and H NMR values could be well assigned to the particular carbon and hydrogen atoms. The equilibria were determined in dimethyl sulfoxide (DMSO) and aqueous trifluoroacetic acid. 

The 1-fluoroquinuclidinium fluoride (NFQNF, 2) precipitates during the reaction and, after treatment with hot, dry acetone to remove quinuclidinium fluoride, is obtained as an extremely hygroscopic white solid which can be assayed iodometrically (reaction with aqueous acetonic KI occurs instantaneously at rt). l-Fluoroquinuclidinium fluoride (2) is readily soluble in water, methanol, ethanol, trifluoroacetic acid, and ethyl acetate, and reasonably so in acetonitrile, but appears to be insoluble in alkanes, arenes, chloromethanes, acetone, diethyl ether, tetrahy-drofuran, dimethylformamide and dimethyl sulfoxide. The fluoride 2 has a melting point of 126-128°C (dec.) and is less flammable than quinuclidine in air, igniting only on direct contact with a flame or after prolonged heating on a metal plate. It does not explode when struck with a hammer.73... 

The first diquaternary salt (67) of 1,7-phenanthroline was prepared using trimethyloxonium fluoroborate in nitromethane.15 The salt is immediately demethylated in the 1-position in dimethyl sulfoxide, trifluoroacetic acid, or water to give 68. If ethylene chloride is used as quaternizing solvent, the monoquaternary salt (68) is obtained. 

Etherification of isohexides with substituted-benzyl chloride in aqueous sodium hydroxide, or by means of sodium hydride in dimethyl sulfoxide, yields mixtures of mono- and bis-ethers, which can be conventionally separated by distillation or by column chromatography.176 The preparation of some phenyl ethers was also described, using the tosylate-phenoxide exchange reaction. Monoethers (88) synthesized in this way were transformed into carbamates (89) by reaction with sodium cyanide-trifluoroacetic acid (see Scheme 18). 

Abbreviations BAL, backbone amide linker BSA, bis(trimethylsilyl)acetamide DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene DCE, dichloroethane DCM, dichloromethane DIC, 2-diisopropylcarbodiimide DIEA, diisopropylethyl amine DMAP, A,A-dimethylaminopyr-idine DMF, dimethylformamide DMSO, dimethyl sulfoxide EDC, l-(3-dimethylaminopro-pyl)-3-ethylcarbodiimide hydrochloride HBTU, [0-(7-azabenzotriazol-l-yl)-l, 1,3,3-tetramethyluronium hexafluorophosphate MCPBA, m-chloroperoxybenzoic acid NMP, N-methylpyrrolidinone NMM, A-methylmorpholine PfP, pentafluorophenol RT, room temperature TFA, trifluoroacetic acid THF, tetrahydrofuran. 

The reaction proceeds stereospecifically, giving sulfoximines from the corresponding enantiomerically enriched sulfoxides without racemization. The NH-sulfoxi-mines can then be obtained after Boc cleavage with trifluoroacetic acid. Bolm et al. applied this reaction in the synthesis of sulfoximines having a benchrotene skeleton (Scheme 3.55) [171]. 

The 1H NMR spectra of parbendazole was recorded with a JEOL-PS 100 NMR spectrometer operating at a frequency of 100 MHz and a magnetic field strength of 2.349 T. Spectra were determined over the region 10.8-0.0 parts per million (ppm), with a sweep time of 250 s. Chemical shifts were recorded as S (delta) ppm downfield from tetra-methylsilane (TMS). Proton noise and off-resonance decoupled 13C NMR spectra were measured on a JEOL FX 90Q Fourier Transform NMR spectrometer operating at 90 MHR and spectral width of 5000 Hz (220 ppm). All measurements were obtained with the compound being dissolved in deuterated dimethyl sulfoxide (DMSO-d6) for dT NMR and in deuterated trifluoroacetic acid (TFA-dx) for 13C NMR. 

They are approximately in agreement with values reported in literature, but the spectrum there was obtained with a HA-100 (23). The nmr shifts appear to be general regardless of solvent. Similar shifts are obtained in pyridine, trifluoroacetic acid and dimethyl sulfoxide. Particularly notable is the substantial downfield shift in the resoncance due to the C 4 proton when the tetracyclines epime-rize at C 4. This is especially convenient as both isomers are usually available and can be distinguished easily in this way. NMR was used to monitor the epimerization of TC since the dimethylamino resonance of TC and its C 4 epimer differ by 0.1 ppm (24). Formation of anhydrotetracycline could also be readily detected through NMR (23). 

Lithium Aluminum Hydride. Reacts violently with trifluoroacetic acid.2 Dimethyl Sulfoxide. Reacts explosively with trifluoroacetic anhydride.3... 

Solvent manufacturer Honeywell Burdick Jackson [39] defines solvents as miscible if the two components can be mixed together in all proportions without forming two separate phases. A solvent miscibility chart (Figure 2.12) is a useful aid for determining which solvent pairs are immiscible and would therefore be potential candidates for use in LLE. More solvent combinations are miscible than immiscible, and more solvents are immiscible with water than with any other solvent. Solvents miscible with water in all proportions include acetone, acetonitrile, dimethyl acetamide, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, ethyl alcohol, glyme, isopropyl alcohol, methanol, 2-methoxyethanol, /V-methyI pyitoI idone. n-propyl alcohol, pyridine, tetrahydrofuran, and trifluoroacetic acid [40]. 

A more classical series of steps have been utilised by Sano et al. in the synthesis of the 2-benzazepines 53 from the aromatic aldehydes 47 and the amine 48 to give the imines 49, followed by reduction to the amines 50, A -formylation to 51, and oxidation to the sulfoxides 52. A modified Pummerer reaction on 52 (with trifluoroacetic acid and BFj.EtjO) was then used to complete the 7-membered ring in yields for this last step ranging from 45% to 78% (e.g. 53, R1 = R2 = H, R3 = OMe, R4 = H 78%) [01H967],... 

Ac, acetyl AIBN, azobis(isobutanonitrile) All, allyl AR, aryl Bn, benzyl f-BOC, ferf-butoxycarbonyl Bu, Butyl Bz, benzoyl CAN, ceric ammonium nitrate Cbz, benzyloxycarbonyl m-CPBA, m-chloroperoxybenzoic acid DAST, diethylaminosulfur trifluoride DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DCC, /V. /V - d i eye I oh e x y I c ar bo -diimide DCM, dichloromethyl DCMME, dichloromethyl methyl ether DDQ, 2,3-dichloro-5,6-dicyano-l,4-benzoquinone DEAD, diethyl azodicarboxylate l-(+)-DET, L-(+)-diethyl tartrate l-DIPT, L-diisopropyl tartrate d-DIPT, D-diisopropyl tartrate DMAP, 4-dimethylaminopyridine DME, 1,2-dimethoxyethane DMF, /V./V-dimethylformamide DMP, 2,2-dimethoxypropane Et, ethyl Im, imidazole KHMDS, potassium hexamethyldisilazane Me, methyl Me2SO, dimethyl sulfoxide MOM, methoxymethyl MOMC1, methoxymethyl chloride Ms, methylsulfonyl MS, molecular sieves NBS, N-bromosuccinimide NIS, /V-iodosuccinimide NMO, /V-methylmorpho-line N-oxide PCC, pyridinium chlorochromate Ph, phenyl PMB, / -methoxvbenzyl PPTs, pyridiniump-toluenesulfonate i-Pr, isopropyl Py, pyridine rt, room temperature TBAF, tetrabutylammonium fluoride TBS, ferf-butyl dimethylsilyl TBDMSC1, f-butylchlorodimethylsilane Tf, trifhioromethylsulfonyl Tf20, trifluoromethylsulfonic anhydride TFA, trifluoroacetic acid THF, tetrahydrofuran TMS, trimethylsilyl TPAP, tetra-n-propylammonium perruthenate / -TsOH. / -toluenesulfonic acid... 

Protection by the A "-allyloxycarbonyl (Aloe) group (Scheme 11) is completely orthogonal with A -Boc but not with A -Fmoc because A "-Aloc, like A "-Z (see Section 2.6.3.3), is cleaved by nucleophiles such as piperidine it is stable to trifluoroacetic acid but is cleaved by Pd(0)-catalyzed allyl transfer to methylaniline in tetrahydrofuran/dimethyl sulfoxide or piperidine/dimethylformamide (1 1 ).P 1... 

The maiin domain of oxidation with dimethyl sulfoxide is the conver-sionofprimary alcoholsinto aldehydes andofsecondaryalcoholsintoketones. These reactions are accomplished under very mild conditions, sometimes at temperatures well below 0 °C. The reactions require the presence of acid catalysts such as acetic anhydride [713, 1008, 1009], trifluoroacetic acid [1010], trifluoroacetic anhydride [1011, 1012, 1013], trifluorometh-anesulfonic acid [1014], phosphoric acid [1015, 1016], phosphorus pentox-ide [1006, 1017], hydrobromic acid [1001], sulfur trioxide [1018], chlorine [1019, 1020], A -bromosuccinimide [997], carbonyl chloride (phosgene) [1021], and oxalyl chloride (the Swem oxidation) [1022, 1023, 1024], Dimethyl sulfoxide also converts sufficiently reactive halogen derivatives. into aldehydes or ketones [998, 999] and epoxides to a-hydroxy ketones at -78 °C [1014]. 

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