Juta Koppel

Pentakis(trifluoromethyl)phenyl, a sterically crowded and electron-withdrawing group: synthesis and acidity of pentakis(trifluoromethyl)benzene, -toluene, -phenol, and -aniline.

A general route to functionalized pentakis(trifluoromethyl)phenyl (C6(CF3)5) derivatives, promising building blocks for designing novel stable carbenes, radical species, superacids, weakly coordinating anions and other practically and theoretically useful species, is presented. This pertrifluoromethylation route proceeds via conveniently pregenerated (trifluoromethyl)copper (CF3Cu) species in DMF, stabilized by addition of 1,3-dimethyl-2-imidazolidinone (DMI). These species react with hexaiodobenzene at ambient temperature to give the potassium pentakis(trifluoromethyl)phenoxide along with hexakis(trifluoromethyl)benzene and pentakis(trifluoromethyl)benzene in a combined yield of 80%. A possible reaction pathway explaining the formation of pentakis(trifluoromethyl)phenoxide is proposed. Pentakis(trifluoromethyl)phenol gives rise to easily functionalized pentakis(trifluoromethyl)chlorobenzene and pentakis(trifluoromethyl)aniline. Pertrifluoromethylation of pentaiodochlorobenzene and pentaiodotoluene allows straightforward access to pentakis(trifluoromethyl)chlorobenzene and pentakis(trifluoromethyl)toluene, respectively. XRD structures of several C6(CF3)5 derivatives were determined and compared with the calculated structures. Due to the steric crowding the aromatic rings in all C6(CF3)5 derivatives are significantly distorted. The gas-phase acidities (Delta Gacid) and pKa values in different solvents (acetonitrile (AN), DMSO, water) for the title compounds and a number of related compounds have been measured. The origin of the acidifying effect of the C6(CF3)5 group has been explored using the isodesmic reactions approach.

Comparison of brönsted acidities of neutral NH-acids in gas phase, dimethyl sulfoxide and water

Abstract The Bronsted acidities of several neutral NH-acids (substituted diphenylamine, substituted anilines and imides) were measured in the gas phase (pulsed FT ICR spectrometry), dimethyl sulfoxide and aqueous solution. Comparison of the Bronsted acidities of neutral NH-acids in the gas phase, dimethyl sulfoxide and water was also carried out. It was shown that substituent effects on the acidity of the studied compounds are significantly attenuated by the transfer of the reaction series of acidic dissociation of neutral acids from the gas phase into dimethyl sulfoxide and water. The strongest solvent-induced attenuation of the substituent effects is characteristic of the meta-substituted anilines whose sensitivity towards substituent effects decreases with transfer from the gas phase into DMSO by 2.83 times and with transfer into water by 4.13 times. At the same time, the reaction series of para and/or ortho-π-acceptor substituted anilines, amides, imides and substituted diphenylamines are less sensitive to a change in gas phase for DMSO or water. In the special case of para-acceptor substituted anilines it was demonstrated that the specific solvation induced an increase in the acidity of the para- and/or ortho-acceptor substituted anilines as compared with the behavior of the corresponding meta-substituted anilines by amounts up to 10 pKa units.

Basicity of 3-aminopropionamidine derivatives in water and dimethyl sulphoxide. Implication for a pivotal step in the synthesis of distamycin A analogues

The acid-base properties of eight 3-aminopropionamidine derivatives R1R2N(CH2)2C((DOUBLE BOND)NH)NR3R4 (1, R1 = R2 = R3 = R4 = H; 2, R1 = R3 = R4 = H, R2 = Me; 3, R1 = R2 = R4 = H, R3 = Me; 4, R1 = R2 = H, R3 = R4 = Me; 5, R1 = Tos, R2 = R3 = R4 = H; 6, R1 = Tos, R2 = Me R3 = R4 = H; 7, R1 = Tos, R2 = R4 = H, R3 = Me; 8, R1 = Tos, R2 = H, R3 = R4 = Me; Tos = 4-toluenesulphonyl) related to the antiviral natural product distamycin A were investigated in water and dimethyl sulphoxide (DMSO). The measured pKa values for the ammonium function in 1–4 in water ranged between 7·48 and 7·73, whereas the corresponding values in DMSO were 9·4 ± 0·3. The amidinium moiety of these compounds displayed pKa values in the range 11·4–12·0 and 13·4–13·6 in water and DMSO, respectively. The tosylamide group in compounds 5–8 was deprotonated in the expected pH region and exhibited pKa values between 9·49 and 10·02 in water, but was considerably less acidic in DMSO (14·5 ≤ pKa ≤ 15·7). The behaviour of the amidinium cation of 5–8 in water and DMSO resembled that of 1–4. The measured pKa values are discussed and the solvent-induced pKa shifts are explained in terms of solvent and substituent effects. The observed pKa differences between the ammonium and the amidinium functions in 1–4 render these compounds suitable intermediates in an alternative synthesis of distamycin A.

Comparison of Brønsted acidities of neutral CH acids in gas phase and dimethyl sulfoxide

The Bronsted acidities of a number of neutral CH-acids (substituted toluenes, aryl- and diarylacetonitriles, fluorenes, ethyl esters of phenylcyanoacetic acids, substituted methanes, etc.) were measured in the gas phase (pulsed FT-ICR spectrometry) and in dimethyl sulfoxide (potentiometric titration). Comparison of the Bronsted acidities of the neutral CH-acids in the gas phase and in dimethyl sulfoxide (DMSO) was also carried out. It was shown that, as a rule, substituent effects on the acidity of the studied compounds are significantly attenuated by the transfer of the reaction series of acidic dissociation of neutral acids from the gas phase into DMSO. The weakest attenuation was monitored in the case of aromatic hydrocarbons, which are the conjugate acids of carbanions with very extensive charge delocalization (fluoradene, substituted fluorenes, aryl-substituted cyclopentadienes and indenes, toluene, diphenyl and triphenylmethanes, etc.). The strongest solvent-induced attenuation of the substituent effects is characteristic of meta-substituted phenylacetonitriles and phenylmalononitriles, whose sensitivity towards substituent effects decreases with transfer from the gas phase into DMSO by up to 2.8–3.3 times. At the same time, the reaction series of para and/or ortho-π-acceptor substituted phenylacetonitriles are less sensitive to a change from the gas phase to DMSO. In the series of α-cyanosubstituted toluenes the solvent attenuation of substitution effects in the benzene ring increases with the successive inclusion of cyano groups into the α-position. In the special case of para-acceptor substituted phenylacetonitriles it was demonstrated that the specific solvation induced an increase in the acidity of the para- and/or ortho-acceptor substituted phenylacetonitriles as compared to the behavior of the corresponding meta-substituted phenylacetonitriles by up to 3.6 pKa units.

The enormous acidifying effect of the supersubstituent NSO2CF3 on the acidity of derivatives of benzenesulfonamide and toluene-p-sulfonamide in the gas phase and in dimethyl sulfoxide

The effect of stepwise replacement of O oxygen atoms by NSO2CF3 fragments in the sulfonyl group of toluene-p-sulfonamide and benzenesulfonamide on their acidity has been studied in the gas phase and dimethyl sulfoxide (DMSO). Incorporation of the first NSO2CF3 group into 4-MeC6H4SO2NH2 increases its gas-phase acidity by 23.6 kcal mol−1. Substituting the second O by the NSO2CF3 group leads to an additional acidity increase of 10.7 kcal mol−1; the total acidity increase is thus 34.3 kcal mol−1 (25 powers of ten!). In DMSO solution the total acidity increase is 13 pKa units (17.7 kcal mol−1). These findings are also supported by computational studies using DFT B3LYP at the 6-31+G* level and the semiempirical PM3 method. The results of this work have potentially important implications for the design of new strongly acidic catalytic materials.

Synthesis and cathodic cleavage of a set of substituted benzenesulfonamides including the corresponding tert-butyl sulfonylcarbamates: pKa of sulfonamides

From a series of substituted benzenesulfonic acids, most of which have previously been employed for the protection of amino functions and including a few such known to facilitate cleavage by acid, benzylamides 1a–k have been derived and studied. Initially their electrochemical cleavage potentials were determined by cyclic voltammetry in order to further explore selective deprotection within this substance group. In parallel, the corresponding tert-butyl sulfonylcarbamates 2a–k have also been prepared and studied. Among the sulfonamides investigated S–N bond cleavage was found to take place over a wide range of potentials from –1.67 to –2.64 V (excluding the nitro derivative), the most acid-labile groups requiring more negative potentials, whereas this cleavage was facilitated by 0.19–0.30 V for the sulfonylcarbamates. Small scale electrolyses of 2 at controlled potential with determination of the cleavage products formed were subsequently performed. For the N-benzylbenzenesulfonamides 1, the pKas in DMSO and in some cases also in water have been determined and found to be in the range 14.0–16.4 and 10.07–11.53, respectively.