RSC Advances PAPER Preparation of carboxylic arylphosphines by Cite this: RSC Adv., 2022, 12, 7103 hydrolysis of the trifluoromethyl group† Daniel Herrera, Daniel Peral and J. Carles Bayón * Triarylphosphines substituted with carboxylic and trifluoromethlyl groups have been prepared by the hydrolysis of trifluoromethyl groups using fuming sulfuric acid and boric acid. The reaction has been studied in a set of homoleptic and heteroleptic trifluoromethylated triarylphosphines and offers a new synthetic procedure for the preparation of carboxylic phosphines with a relatively simple methodology. The degree of carboxylation is modulated by the reaction conditions and is sensitive to the substitution pattern of the starting trifluoromethylated phosphines. A pH-dependent procedure based on the amphiphilic character of these phosphines was developed for their separation and purification. The Received 20th January 2022 Accepted 24th February 2022 electronic properties of the synthesized carboxylic-trifluoromethylated phosphines have been analyzed by 31P NMR of the corresponding selenide derivatives. Finally, the structures of two palladium complexes, DOI: 10.1039/d2ra00420h containing the para and meta carboxylic-trifluoromethylated phosphines are also described, showing rsc.li/rsc-advances different dimeric structures. hydrolysis of the nitrile group has also been found to yield Introduction mono-, di- and tri-carboxylic triarylphosphines, and has also Phosphines containing carboxylic groups have been widely re- been applied to some alkyl phosphines.6 Finally, Pd(II)-catalysed ported in the literature. The amphiphilic behaviour that the P–C coupling has been also used for the preparation of carboxylic groups confer to the phosphines has been found of carboxylic phosphines.7 interest in several applications such as their use as water- Carbonyl compounds can be prepared from a triuoromethyl soluble reducing agents of disulde bonds1 or as ligands in group under strong acidic conditions. In 1943, Simons and transition metal-based catalysis, either by coordination through Ramler8 and Gilman and Blume9 reported the hydrolysis of the the phosphorus atom2 or acting as chelating ligands.3 Moreover, triuoromethyl group, using sulfuric acid, as a methodology to the carboxylic derivatives of triphenylphosphine have been used establish the structure of different triuoromethylbenzene as building blocks in the preparation of porous coordination derivatives. Later, Le Fave et al. reported the formation of benzoic materials.4 In spite of the versatility of carboxylic phosphines, acids from the hydrolysis of triuoromethylbenzene and deriva- certain considerations should be born in mind in regard to their tives, using concentrated sulfuric acid, followed by the treatment preparation. The most extended procedures for the general of the mixture with water.10 They also proved that benzoate esters synthesis of phosphines, such as the reaction of chlor- could be obtained when treating the reaction mixtures with ophosphines or phosphorus trichloride with Grignard reagents alcohols instead of water.11 Furthermore, the same authors or organolithium derivatives, as well as the nucleophilic reac- described the preparation of phthalic acids by hydrolysis of the tion between alkali phosphides and haloderivatives, are not corresponding bis(triuoromethyl)benzenes in an equimolar compatible with the presence of acidic protons. In the last case, mixture of sulfuric acid and chlorosulfuric acid.12 In spite of these the incompatibility between the phosphide anions and the early publications, the reaction of hydrolysis of the tri- carboxylic acid can be overcome using strong basic conditions, uoromethyl group has not attracted much interest and only although sometimes this is accompanied by solubility issues. In a few more examples have been reported aer the pioneering this regard, several other alternative strategies have been studies of Le Fave. Wen and co-workers applied the reaction of developed for the synthesis of carboxylic phosphines. Ravindar hydrolysis, using fuming sulfuric acid, in the preparation of et al. reported the reaction of carbonation of organolithium cholesteryl p-peruoroalkyl benzoates.13 Platonov and co-workers derivatives to yield monocarboxylic triarylphosphines.5 The showed the formation of peruorobenzoic acids from the reac- tion of the corresponding peruorotoluene derivative with Department of Chemistry, Universitat Autònoma de Barcelona, 08193 Cerdanyola del CF3CO2H/SbF5 and the subsequent aqueous treatment.14 Finally, Vallés, Spain. E-mail: joancarles.bayon@uab.cat Kethe et al. studied the hydrolysis of one triuoromethyl group in † Electronic supplementary information (ESI) available. CCDC 2097178 and 1,3,5-tris(triuoromethyl)benzene with either triic acid or uo- 2106238. For ESI and crystallographic data in CIF or other electronic format see rosulfuric acid.15 DOI: 10.1039/d2ra00420h © 2022 The Author(s). Published by the Royal Society of Chemistry RSC Adv., 2022, 12, 7103–7114 | 7103 RSC Advances Paper Despite the above mentioned applications of the hydrolysis also structurally characterized showing different supramolec- of the triuoromethyl group, to the best of our knowledge, no ular patterns, illustrating the capability of this family of ligands precedents are known about the application of this reaction in to build diverse intermolecular networks. the synthesis of phosphines. We envisioned the use of fuming sulfuric acid in combination with boric acid to promote the Results and discussion hydrolysis of the triuoromethyl group in triuoromethylated triarylphosphines. Amongst the available superacid systems, The synthesis of carboxylic triarylphosphines was carried out fuming sulfuric acid is strong (H0 up to 14.9 in 65 wt% SO3 from the hydrolysis of the triuoromethyl group of a series of oleum),16 non-expensive and, most importantly, with a relatively triarylphosphines with different substitution pattern, Scheme 1. lower oxidation power compared to other stronger super acids The reaction was performed using a highly acidic media such as magic acid (i.e. FSO3H$SbF5). Moreover, it has been prepared with a mixture of boric acid and fuming sulfuric acid previously studied in the sulfonation of phosphines.17 Herr- (oleum). The ne tuning of the reaction conditions allows the mann and co-workers showed that the oxidizing power of control of the yield and selectivity of the reaction. The protec- fuming sulfuric acid could be reduced in combination with tion towards the oxidation of the phosphines under these highly boric acid thus preventing the oxidation of the phosphines acidic conditions takes place through the protonation of the during the process of sulfonation.17a In this sense, the studies of phosphorus atom.17a For this reason, complete solubility of the Gillespie and co-workers showed that the addition of boric acid phosphines is necessary before the addition of fuming sulfuric to sulfuric acid generates a strong superacid of the sulfuric acid acid. It is important to notice that water is formed when mixing system, H3SO4[B(OSO3H)4].18 More recently, Peral et al. reported H3BO3 and sulfuric acid, previous to the addition of the phos- the use of oleum and boric acid in the sulfonation of the phines, eqn (1),17a,18 thus changing the polarity of the media and strongly deactivated triuoromethylated phosphines with decreasing the acidity of the mixture. Therefore, sulfur trioxide minor yields of phosphine oxides.17b,c from oleum is required to react with water shiing the equi- Based on the previous examples, the reaction of hydrolysis of librium of eqn (1) towards the formation of the superacid. the triuoromethyl group offers a new synthetic procedure to obtain carboxylic arylphosphines through a relatively simple H3BO3 + 2H2SO4 + 3SO3 % H3SO4+ + B(OSO3H)4 (1) procedure. In this methodology, the triuoromethyl group will be used as a masked carboxylic acid, overcoming the difficulties that arise from the incompatibility of carboxylic acids with the As it will be explained below, the superacid plays an impor- reagents commonly used in the preparation of phosphines. tant role, not only protecting the phosphines from oxidation, Most interestingly, this methodology provides the preparation but also in the hydrolysis of the triuoromethyl groups. of arylphosphines containing both carboxylic and tri- uoromethyl groups. On the one hand, the carboxylic group Synthesis of carboxylic phosphines from homoleptic confers chemical versatility to phosphines, covering a wide triuoromethylated phosphines variety of applications, including those derived from the The hydrolysis of the triuoromethyl groups of three homo- amphiphilic character of the carboxylic group. On the other leptic phosphines (SP1, SP2, SP3) were rstly studied. hand, the triuoromethyl group confers greater p-acidity to the In a preliminary set of experiments, the para-substituted phosphines, which turns into a higher stability towards their tris(4-triuoromethylphenyl)phosphine (SP1) and the chosen oxidation.17c,19 Phosphines with p-acidic character have proven amount of boric acid were dissolved in sulfuric acid before the to increase the activity of certain transition metal-catalysed addition of 65% SO3 fuming sulfuric acid. The evolution of the reactions such as some C–C couplings20 and carbonylations.17c,21 reaction was monitored by aliquoting the sulfuric mixture. Aer A few examples of carboxylic and triuoromethylated aryl- quenching the samples in cold water, the phosphines were phosphines have been previously described in the literature. extracted with diethyl ether and analysed by 31P{1H} NMR to Reek's group reported the synthesis of carboxylic and tri- quantify the distribution phosphorus compounds present in uoromethylated phosphines through a Pd catalysed P–C the mixture. Control analysis of the aqueous layers showed that coupling.22 More recently, Starkov et al. described the synthesis all phosphorus compounds were completely extracted into the of an ortho-carboxylic triuoromethylated phosphine by organic phase. Three carboxylic products were observed as a several-steps methodology in which the P–C bond is con- result of the hydrolysis of one, two or all the triuoromethyl structed through a Cu-mediated coupling with the carboxylic groups. group protected as methyl ester.23 The reaction was explored and optimized at different Here we report the preparation of carboxylic phosphines by concentrations of phosphine, H3BO3 and SO3 (ESI Fig. S1†). The the reaction of hydrolysis of the triuoromethyl group in tri- reaction rates of the hydrolysis of the triuoromethyl group uoromethylated triarylphosphines, using fuming sulfuric acid were observed to strongly depend on the concentration of and boric acid. The carboxylic-triuoromethylated phosphines H3BO3 and SO3. High concentrations of SO3 (above 12 M) gave have been successfully separated and puried, and their elec- faster reaction rates although led to the complete oxidation of tronic properties have been studied by 31P{1H} NMR using the the phosphine products at short reaction times. As expected, selenium derivatives. Palladium complexes of the para and meta increasing H3BO3 concentration was found to decrease the rate carboxylic and bis(triuromethylated) triarylphosphine were of phosphine oxidation. However, and contrary to what was 7104 | RSC Adv., 2022, 12, 7103–7114 © 2022 The Author(s). Published by the Royal Society of Chemistry Paper RSC Advances Scheme 1 Synthesis of carboxylic triarylphosphines from trifluoromethylated phosphines. (i) H3BO3/H2SO4/SO3. (ii) H2O. observed for the reactions of sulfonation of triar- Moreover, in this experiment, only traces of the tricarboxylic ylphosphines,17b,c the use of H3BO3 showed a positive effect on phosphine TC1 were detected (ca. 2%). the rate of the triuoromethyl hydrolysis reaction. The most Fine tuning of the reaction conditions and reaction time suitable conditions for the preparation of the monocarboxylic allows the control of the composition of the reaction mixture. phosphine MC1 and the dicarboxylic phosphine DC1 were For the preparation of the monocarboxylic phosphine MC1, found at concentrations of SO3 and H3BO3 of 10.5 M and 0.8 M, reaction times can be shortened to 4 hours at the optimized respectively, with initial phosphine concentration of 0.15 M. conditions described above, to get 50% of this carboxylic Fig. 1 shows the graphical representation of the consumption of phosphine together with the unreacted phosphine SP1, which the triuoromethylated starting phosphine SP1 together with the evolution of the monocarboxylic phosphine MC1, the dicarboxylic phosphine DC1 and the tricarboxylic phosphine TC1 under the optimized conditions. In addition to the molar fraction of the phosphines, the sum of phosphine oxides present in the mixture is also represented. In the optimized conditions, aer 1 h, the reaction mixture showed 25% of the monocarboxylic compound MC1, together with 11% of phosphine oxides. Aer 3 h of reaction, the amount of MC1 increased to 45% and 10% of the dicarboxylic phos- phine DC1 was detected, with no signicant variation of the amount of phosphine oxides. When the reaction was analyzed aer 21 h, the mixture showed complete consumption of the starting phosphine SP1, it being the dicarboxylic phosphine DC1 the major component of the mixture (53%) together with Fig. 1 Evolution of the reaction of hydrolysis in phosphine SP1 in 22% of the monocarboxylic phosphine MC1 and 23% of oxides. sulfuric acid with time. Reaction conditions [SP1]: ¼ 0.15 M, [H3BO3] ¼ 0.8 M, [SO3] ¼ 10.5 M. © 2022 The Author(s). Published by the Royal Society of Chemistry RSC Adv., 2022, 12, 7103–7114 | 7105 RSC Advances Paper aer proper separation, could be reused in a new reaction. If the desired product is the dicarboxylic phosphine DC1, the reaction mixture is quenched aer 14 h to obtain a 50% mixture of MC1 and DC1, Table 1. Moreover, increasing the concentration of H3BO3 to 2.4 M, it is possible to obtain 46% of the tricarboxylic phosphine TC1, together with 36% of the dicarboxylic phos- phine DC1 and below 25% of phosphine oxides aer 20 hours. Although such conditions need fairly long reaction times, they open a new synthetic approach to the already known procedures for preparing this tricarboxylic phosphine.6 The synthesis of meta-carboxylic phosphines was also Chart 1 Trifluoromethylated phosphine SP3. essayed from the homoleptic triuoromethylated phosphine SP2 using the same optimized conditions than for the para- substituted phosphine SP1. The evolution of the reaction ana- oxide and a dicarboxylic phosphine oxide. However, the pattern lysed by 31P NMR also showed the hydrolysis of one, two and of carboxylation in the dicarboxylic compound (i.e. in the same three triuoromethyl groups producing the monocarboxylic or different ring), could not be determined. phosphine MC2, the dicarboxylic phosphine DC2 and the tricarboxylic phosphine TC2, respectively, Scheme 1. Interest- ingly, the rate of the reaction of hydrolysis of the triuoromethyl Synthesis of carboxylic phosphines from heteroleptic groups in meta is much faster than that of the triuoromethyl triuoromethylated phosphine groups in para position (ESI Fig. S2†). For the synthesis of the Given the feasibility of the synthesis of carboxylic phosphines monocarboxylic phosphine MC2, the reaction is quenched aer from the hydrolysis of the para (SP1) and meta-substituted (SP2) 0.5 h to obtain a mixture of 48% of SP2 and 41% of MC2 with triuoromethylated phosphines and the poor reactivity of the only traces of the dicarboxylic phosphine. For the preparation of triuoromethyl groups in the 3,5-substituted phosphines (SP3), the dicarboxylic phosphine DC2, the reaction was le for 20 h to it was appealing to study the reaction of hydrolysis in hetero- obtain a mixture of 6% of MC2, 60% of DC2 and 20% of the leptic phosphines containing both patterns of substitution, tricarboxylic phosphine TC2, Table 1. As previously shown for (SP4, SP5 in Scheme 1 and SP6 and SP7 in Chart 2). SP1, with the meta-isomer SP2, it is also possible to tune the As a general trend, low solubility of the heteroleptic phos- composition of the mixture before the separation process phines in the H3BO3/H2SO4 mixture, previous to the addition of adjusting the reaction conditions. oleum, was observed yielding to high percentages of oxides at Based on the faster reactivity of the triuoromethyl groups in short reaction times. The solubility of the phosphines meta position with respect to the para substituted phosphines, decreased when increasing the number of triuoromethyl the reaction of hydrolysis of the triuoromethyl groups of the groups and this was more evident with the para-substituted 3,5-substituted phosphine SP3 was tested, Chart 1. Unexpect- heteroleptic phosphines (SP6 and SP7). Moreover, the hydro- edly, the hydrolysis in this doubly meta-substituted phosphine lysis of the triuoromethyl group with the heteroleptic phos- SP3 was much slower than for the hydrolysis of the single- phines showed slower reaction rates for the para-isomers (SP6 substituted phosphine SP2. Using the optimized conditions and SP7) than for the meta-substituted phosphines (SP4 and for the preparation of the para- and meta-carboxylic phos- SP5), a trend already observed for the homoleptic phosphines phines, the progress of the reaction for SP3, analysed by NMR, SP1 and SP2. Furthermore, hydrolysis of the triuoromethyls at showed considerable slower rates for the hydrolysis of the tri- 3,5-positions was not detected. It is important to note that the uoromethyl groups than in the case of SP1 or SP2, yielding reaction rates were found to be lower when increasing the phosphine oxides as main products. Mass spectrometry anal- number of triuoromethyls in the phosphines (ESI Fig. S3†). ysis of the reaction mixture aer 20 h conrmed the presence of Optimized conditions were found for the synthesis of the the monocarboxylic phosphine, the monocarboxylic phosphine meta-carboxylic phosphines MC4, DC4 and MC5, as shown in Table 1 Optimized conditions for the synthesis of carboxylic and trifluoromethylated phosphines Reaction conditions Hydrolysis yield (%) [SO3] [H3BO3] Carboxylic phosphine Starting phosphine [SP] (M) (M) (M) Time (h) SP MC DC TC Oxides MC1 SP1 0.15 10.5 0.8 4 46 46 0 0 8 DC1 SP1 0.15 10.5 0.8 14 4 40 48 0 8 MC2 SP2 0.15 10.5 0.8 0.5 48 41 6 0 5 DC2 SP2 0.15 10.5 0.8 20 0 6 60 20 14 MC4–DC4 SP4 0.07 9 0.8 18 9 48 34 — 9 MC5 SP5 0.08 9 0.4 50 0 63 — — 37 7106 | RSC Adv., 2022, 12, 7103–7114 © 2022 The Author(s). Published by the Royal Society of Chemistry Paper RSC Advances carboxylic-triuoromethylated phosphines has been developed based on the pH-dependent solubility of carboxylic acids. The separation process has been optimized for a mixture containing all the possible phosphine compounds derived from the reaction of hydrolysis of triuoromethylated phosphines, that is, starting phosphine (SP), monocarboxylic (MC), dicarboxylic (DC), tricar- boxylic (TC) and phosphine oxides, to cover all possible Chart 2 Heteroleptic trifluoromethylated phosphines SP6 and SP7. scenarios. A scheme of the separation is presented in Fig. 2. Aer the hydrolysis reaction, the mixture was poured on ice and the phosphorus compounds were extracted from the Table 1. Long reaction times were needed to obtain the aqueous sulfuric media using diethyl ether. Water was added to carboxylic phosphines in moderate yields, due to the diluted the previous Et2O solution, yielding a new biphasic organic- phosphine concentrations required to minimize the initial aqueous system. The aqueous phase was brought to pH 6.0 oxidation of SP4 and SP5. using an aqueous solution of NaOH to completely extract the For the para-heteroleptic phosphines SP6 and SP7 the reac- tricarboxylated phosphine (TC) into the aqueous phase, tion was found to be very slow. The large amount of phosphine together with its oxide and the oxide of DC, when present. Aer oxides and the slow reactivity of the para-triuoromethyls phase separation, water was added again to the ethereal phase jeopardize the preparation and isolation of the corresponding and further basication to reach a pH of about 7.5 allowed the carboxylic phosphines. Aer several attempts to optimize the extraction of the dicarboxylic phosphine (DC) into the aqueous reactions, no suitable conditions were found for the preparation solution. Within this range of pH, also the oxide of the mono- and isolation of the corresponding carboxylic phosphines. carboxylic compound (MC) is extracted. The acidication of Therefore, other reported procedures would be more appro- each of the aqueous phases containing the sodium salts of the priate for the formation of these carboxylic phosphines.5,7,22,23 dicarboxylate and tricarboxylate phosphines to pH 2, allowed the re-extraction of the phosphines in the acidic form in diethyl ether. Separation and purication of the carboxylic phosphines The extraction of the monocarboxylic phosphine (MC) from In all the synthetic procedures described above, a mixture of the ethereal phase by further increasing the pH of the aqueous different phosphines is obtained aer the reaction of the tri- phase is not possible because of the formation of stable emul- uoromethylated starting phosphines with H3BO3 and oleum. A sions. Therefore, an alternative procedure was developed general methodology for the separation and purication of the starting by vacuum evaporation of the diethyl ether. To the solid Fig. 2 Separation of the phosphines products of the reaction of hydrolysis of the trifluoromethyl group. © 2022 The Author(s). Published by the Royal Society of Chemistry RSC Adv., 2022, 12, 7103–7114 | 7107 RSC Advances Paper residue containing SP and MC, a solution of 10% NaOH in methanol was added dropwise. Aer complete deprotonation of the carboxylic group of MC, monitored by TLC (CH2Cl2), methanol was vacuum evaporated and cyclohexane was added to the solid residue to extract the unreacted starting phosphine (SP). Finally, phosphine MC was recovered again as carboxylic acid by acidication to pH 2 followed by extraction in diethyl ether. With this procedure, it was possible to prepare a whole set of mono- and dicarboxylic triuoromethylated triarylphosphines, Scheme 1.24,25 These phosphines are a proof concept of the application of the hydrolysis of the triuoromethyl group in triuoromethylated arylphosphines using sulfuric fuming acid and H3BO3, and open a new synthetic route in the synthesis of these sort of compounds. Reaction mechanism The nature of the highly acidic medium used for the hydro- lysis of the triuoromethyl groups hampers the study of the reaction mechanism. Nevertheless, with 31P{1H} and 19F{1H} Scheme 2 Proposed reaction mechanism of the hydrolysis of the NMR experiments it is possible to analyse in situ the trifluoromethyl group in trifluoromethylated phosphines with sulfuric progression of the reaction. Fig. 3 shows the evolution of the acid. hydrolysis of the triuoromethyl group in the p-tris(tri- uoromethylphenyl)phosphine (SP1) monitored by 31P{1H} and 19F{1H} NMR. In a rst step, strong interaction between the acidic protons Importantly, a singlet in the 19F{1H} spectra at 42.6 ppm, of the superacid and uorine promotes the C–F bond cleavage corresponding to the –OSO2F moiety26 was detected. The releasing a HF molecule and generating the diuorobenzylic intensity of this signal increased as new phosphine signals were carbocation (A), in analogy with previously reported experi- observed in the 31P{1H} NMR spectra. Besides the signal of the mental and theoretical studies.27 Next, the nucleophilic attack triuoromethyl groups (around 63 ppm), no other uorinated of a molecule of H2SO4 on the carbocation A yields the forma- species were found in these experiments. tion of the hydrogensulfuric ester B. The reaction may be fav- Based on the NMR experiments and the previously reported oured by the highly electrophilic uorinated carbocation. reactions of triuoromethylated aryl compounds in acidic Following, the concerted elimination of HSO3F (ca. 40–42 ppm media,15,27 a mechanism for the hydrolysis of the tri- in 19F{1H}) would give the corresponding acyl uoride (C) uoromethyl group in triuoromethylated triarylphosphines similarly to previously reported studies.15,27b Finally, the acyl using fuming sulfuric acid and H3BO3 can be postulated, uoride (C) would react with sulfuric acid to yield the mixed Scheme 2. sulfonic-carboxylic anhydride (D).28 Although the formation of mixed anhydrides by addition of SO3 to acyl uorides has been reported in the literature,26 this option was discarded consid- ering that such reaction requires the use of pure SO3.29 More- over, the signal for the corresponding uorinated mixed anhydride in 19F{1H} NMR (above 45 ppm) was not detected. Aer quenching the reaction in water, D is hydrolysed to form the carboxylic acid (E). It is worth mentioning that neither the signal for the uorinated carbocation (A) (ca. 23 ppm)30 nor the corresponding signal for the acyl uoride (C) (ca. 17.7 ppm)31 or any other intermediates were detected in the 19F{1H} NMR experiments. Therefore, the elimination of HF to form the car- bocation (A) is likely to be the rate determining reaction step, in agreement with the mechanism proposed by Kethe et al. in the Fig. 3 Evolution of the reaction of hydrolysis in phosphine SP1. Analysis of the crude reaction by 31P{1H} (101.27 MHz) (left) and 19F{1H} hydrolysis of the triuoromethyl group in tri- NMR (235.4 MHz) (right). Signals (intensity and position) relative to uoromethylbencenes using triic acid or uorosufuric acid.15 NH4PF6 used as internal standard (144.45 ppm and 72.65 ppm, In the proposed mechanism, H3BO3 and SO3 would be respectively). d in ppm. In 31P{1H} NMR, only phosphine region is involved in the generation of the superacid mixture. The 11B shown. p1, m1 and d1 refer to the precursors of phosphines SP1, MC1, NMR spectra of the reaction mixtures containing phosphine, and DC1 in sulfuric medium. Reaction conditions: [phosphine] ¼ 0.16 M, [H3BO3] ¼ 0.8 M, [SO3] ¼ 11.5 M. sulfuric acid, oleum and boric acid only showed the tetrahedral 7108 | RSC Adv., 2022, 12, 7103–7114 © 2022 The Author(s). Published by the Royal Society of Chemistry Paper RSC Advances species B(OSO3H)4 (ESI Fig. S4†). Gillespie and co-workers hydrolysis of each triuoromethyl group producing a new showed that binary mixtures of sulfuric acid with either carboxylic group causes a moderate decrease, between 2 and H3BO3 or SO3 give rise to an increase in the acidity of the 5 Hz, in the 1JPSe of the phosphine selenides, consistent with media.16,18 In the case of the present work, the increase in the the decrease in the electron withdrawing power of the acidity produced by SO3 and H3BO3 would contribute to the C–F substituents. In previous works,19,33 it has been proven that the bond cleavage in the rst step of the reaction. introduction of triuoromethyl groups in triarylphosphines Based on the proposed mechanism, the different reaction was cumulative and resulted in the increase of 12 Hz in the 1 rates between phosphines with different substitution JPSe, regardless of the position of the group. Same observation pattern can be explained through the resonant structures. was found in the case of the triuoromethylated-carboxylic Since phosphines are protonated under the reaction condi- phosphines. Similarly, the introduction of carboxylic moie- tions, the formation of the diuorobenzylic carbocation (A) ties is also cumulative and adds 9 Hz to the 1JPSe. Conse- implies the generation of a second positive charge on the quently, eqn (2) predicts the values of the 1JPSe in molecule. While in para-substituted phosphines the positive triuoromethylated and/or carboxylic triarylphosphines with charge of the phosphonium can be delocalised at the adja- an error #3 Hz cent atom to the carbocation, in meta-substituted phos- 1 phines this charge is never localised next to the other (ESI JPSe ¼ 731 + 12n + 9m (2) Fig. S5†). Therefore, the formation of the diuorobenzylic carbocation would be more favourable when the tri- where n and m are the number of triuoromethyl and carboxylic uoromethyl group is in meta-position than when located in groups in the phosphine, respectively, regardless of their posi- para. Moreover, the extremely low reaction rates observed tion in the ring. with those triuoromethyls in 3,5-positions might be attributed to inductive effects. Trans-PdCl2L2 complexes of phosphines MC1 and MC2 The two monocarboxylic phosphines were used to synthesise Study of the s-basicity of the triuoromethylated-carboxylic the corresponding trans-PdCl2L2 (L ¼ MC1 and MC2) phosphines: synthesis of the phosphine selenides complexes crystals structures of both complexes were solved Phosphines have been widely studied as ligands in showing the formation of different dimeric structures by transition-metal catalysed reactions. The stereoelectronic hydrogen bonding. properties of these ligands are determined by their substit- Both palladium complexes showed a slightly distorted uents and play an essential role on the catalytic performance. square-planar geometry. The para-isomer PdCl2(MC1)2 was ob- Selenide derivatives have been used as a simple tool to study tained as a dimeric structure where complexes are bridged by the s-donation properties of phosphines through the 1JPSe a carboxylic acid group of one of the phosphines of each of the coupling of the 77Se isotopomer, measured by 31P NMR.19,32,33 monomers. The other carboxylic phosphine interacts through The selenide derivatives of the carboxylic- H-bonding with a molecule of acetone, Fig. 4. The meta-isomer triuoromethylated phosphines have been prepared PdCl2(MC2)2 also forms a dimeric structure. However, in this following a previously reported methodology in tri- case, both carboxylic phosphines participate in the H-bond uoromethylated triarylphosphines.19 network, resulting in a cage type structure, Fig. 5. Inside this As previously observed in triuoromethylated phosphines, cage, badly disordered solvent molecules were observed, in the the 1JPSe increases with the number of triuoromethyl groups, shape of residual peaks, fenced by the aromatic rings with the thus decreasing the basicity of the ligands (ESI Table S1†). The triuoromethyl substituents. Fig. 4 Stick representation of the dimeric structure of the complex of trans-[PdCl2(MC1)2]$acetone. Only one conformation of the disordered CF3 is shown. Hydrogen bond distances (Å): O1–O2, 2.612(3); O3–O1S, 2.708(5). © 2022 The Author(s). Published by the Royal Society of Chemistry RSC Adv., 2022, 12, 7103–7114 | 7109 RSC Advances Paper Experimental General procedure and reagents Unless otherwise mentioned, all the synthetic manipulations were performed under nitrogen atmosphere using standard Schlenk techniques.34 Solvents and liquid reagents were deox- ygenated by bubbling nitrogen for 10–15 minutes. General chemical reagents and solvents were purchased from commer- cial sources and, otherwise specied were used without further purication. Anhydrous solvents and reagents were used when required and were dried by using different standard proce- dures.35 The NMR spectra were recorded in a Bruker Avance 250 and a Bruker Avance III 400 at the Servei de Ressonància Fig. 5 Stick representation of the dimeric structure of the complex of Magnètica Nuclear at the UAB. Chemical shis in 1H and 13C trans-[PdCl2(MC2)2]. Only one conformation of the disordered CF3 is shown. Hydrogen bond distances (Å): O1–O4, 2.673(9); O2–O3, NMR are relative to the signal of the solvent.36 In 31P NMR 2.608(8). chemical shis are relative to 85% H3PO4 (0.0 ppm), used as external standard. For 19F NMR and 11B NMR experiments the signals are relative to urobenzene (113.15 ppm with respect to CFCl3) and BF3$Et2O (0.0 ppm), respectively. Unless other- Conclusions wise stated, all the NMR experiments were performed at 298 K. The reaction of hydrolysis of the triuoromethyl group using High resolution mass-spectrometry analyses and elemental fuming sulfuric acid and H3BO3 allows the preparation of analyses (C and H) were performed by the Servei d'Anàlisi Quı́- carboxylic and triuoromethylated triarylphosphines. The mica at UAB in a Bruker microTOF spectrometer coupled to an reactivity of the phosphines towards the hydrolysis of the tri- Apollo II electrospray source (ESI) and a Thermo Fisher Scien- uoromethyl group depends on the relative position of this tic Flash EA 2000 CHNS, respectively. group with respect to the phosphorus atom, with meta-posi- Synthesis of the triuoromethylated triarylphosphines SP1– tion showing the fastest rate. The number of triuoromethyl SP7 was performed according to the previously reported meth- groups present in the phosphines also inuences the rate of odologies in the literature.19,37 the reaction. Lower reactivity was found when increasing the number of triuoromethyl groups. The reaction mechanism of Synthesis of carboxylic phosphines38 the hydrolysis of the triuoromethylated phosphines in the conditions described in the present work has been proposed 4-(Bis(4-(triuoromethyl)phenyl)phosphanyl)benzoic acid based on in situ NMR experiments. The differences observed in (MC1) and 4,40 -((4-(triuoromethyl)phenyl)phosphanediyl) the rate of the reaction between the para- and the meta- dibenzoic acid (DC1). In a typical reaction, 3.5 g of tris(4- substituted phosphines are consistent with the formation of triuoromethylphenyl)phosphine (SP1) (7.5 mmol) were dis- a diuorobenzyl carbocation in the rate determining step of solved in 15 ml of a solution of boric acid (2.3 g, 37.2 mmol) in the reaction. 98% sulfuric acid at 0  C. A strong red or orange solution was The separation and purication of the phosphines was obtained once the phosphine was completely dissolved. At this carried out by a pH-dependent procedure, based on the point, the solution was kept at 0  C and 32.5 ml of 65% SO3 amphiphilic character of the carboxylic moiety. The reaction fuming sulfuric acid (0.53 mol SO3) were slowly added during 30 has been successfully optimized to prepare seven carboxylic and minutes with vigorous stirring. The dark brown mixture was triuoromethylated phosphines in fair to good yields. then further stirred at room temperature for 14 h to give The s-donation properties of the carboxylic- a mixture of ca. 42% of monocarboxylic phosphine MC1, 50% of triuoromethylated phosphines was studied by means of the dicarboxylic DC1 and 8% of unreacted phosphine SP1. It is 31 1 P{ H} NMR spectra of the selenide derivatives. Both carboxylic advisable to monitor the evolution of the reaction by 31P{1H} and triuoromethyl groups decrease the s-basicity character of NMR since the rate of the reaction is fairly sensitive to the the phosphines although, as expected, triuoromethyls have concentration of SO3 in oleum. The reaction mixture was then a larger inuence. The correlation between the experimental gently poured on 150 g of deoxygenated ice, which was prepared values of 1JPSe and the number of carboxylic and triuoromethyl by freezing 150 ml of deoxygenated water. The resulting brown groups was empirically studied allowing the prediction of the s- slurry was extracted 3 times with 100 ml of Et2O. The organic donation properties of para- and meta-substituted carboxylic- phases were combined and washed 2 times with 50 ml of brine. triuoromethylated triarylphosphines. The separation of the phosphine compounds was then carried The trans-PdCl2(MC)2 complexes of carboxylic phosphines out by means of extractions in water at different pH. Firstly, the MC1 and MC2 were synthesised. Their crystal structures show volume of organic solvent was reduced to ca. 100 ml and 100 ml the diversity of framework that complexes of these ligands can of water were added. The aqueous phase was brought to pH 6.0 produce. by addition of 5% aqueous NaOH, while stirring the biphasic mixture. Once the phases were separated, the pH of the aqueous 7110 | RSC Adv., 2022, 12, 7103–7114 © 2022 The Author(s). Published by the Royal Society of Chemistry Paper RSC Advances phase was measured and corrected if necessary. At this pH, both NMR (100.61 MHz, CD3OD), d (ppm): 169.2 (s, CO2H); 142.8 (d, the oxide of phosphine DC1 and the tricarboxylic phosphine C1{C6H4CO2H}, 1JCP ¼ 13.7 Hz); 142.7 (d, C1{C6H4CF3}, 1JCP ¼ TC1, if present, are extracted as sodium salts in the aqueous 14.2 Hz); 135.3 (d, C2{C6H4CF3}, 2JCP ¼ 20.0 Hz); 134.7 (d, phase which was therefore discarded. Next fresh water (100 ml) C2{C6H4CO2H}, 2JCP ¼ 20.1 Hz); 132.9 (s, C4{C6H4COOH}); 132.2 was added to the organic phase and the pH of the aqueous (q, C4{C6H4CF3}, 2JCF ¼ 32.7 Hz); 131.0 (d, C3{C6H4CO2H}, 3JCP ¼ solution was brought to 7.6, following the procedure described 7.0 Hz); 126.5 (dq, C3{C6H4CF3}, 3JCP ¼ 7.0H, 3JCF ¼ 3.7 Hz); above. At this pH, phosphine DC1 is extracted into the aqueous 125.4 (q, CF3, 1JCF ¼ 271.2 Hz). 19F{1H} NMR (235.39 MHz, phase as sodium salt. Aer decantation, the organic phase was CD3OD), d (ppm): 62.0 (s). HR-MS (ESI m/z) [M–H]: calcu- extracted again with 50 ml of water at pH 7.6. The organic layer lated for [C21H13F3O4P] 417.0509; found 417.0503. Elemental was kept under nitrogen in a round–round bottom ask for later analysis: calculated for C21H14F3O4P$1/2H2O: C, 59.03; H, 3.54; treatment. The aqueous phases were combined and, aer found: C, 59.19; H, 3.36. acidication to ca. pH 2 with 10% aqueous H2SO4, phosphine 3-(Bis(3-(triuoromethyl)phenyl)phosphanyl)benzoic acid DC1 was extracted in the acidic form with 3 portions of 30 ml of (MC2) and 3,30 -((3-(triuoromethyl)phenyl)phosphanediyl)diben- Et2O. The organic layers were dried over MgSO4 and the solvent zoic acid (DC2). The same procedure and reaction conditions as was vacuum evaporated to give 1.1 g (35% yield) of the dicar- described for the para-substituted phosphines were followed in boxylic phosphine (DC1) in its hemihydrate form, as a white the hydrolysis of the meta-substituted phosphine SP2. In this case, solid in purity higher than 95%. The organic phase separated at when the dicarboxylic phosphine DC2 was the aimed product of pH 7.6, which contained the monocarboxylic phosphine MC1 the synthesis, the triuoromethylated phosphine SP2 was allowed and the starting phosphine SP1, was vacuum evaporated and to react with oleum for 20 h, yielding a mixture composed of 6% treated with a solution of NaOH (5%, in methanol) until of MC2, 60% of DC2 and 20% of the tricarboxylic phosphine TC2. complete neutralisation of the carboxylic group of MC1. This If, instead, the monocarboxylic phosphine MC2 was aimed, the reaction can be monitored by TLC in silica. Then, the solvent reaction with oleum was stopped aer 0.5 h, yielding 48% of was vacuum evaporated to dryness and the resulting solid unreacted phosphine SP2, 41% of phosphine MC2 and 6% of residue was extracted with cyclohexane to remove phosphine DC2. Reaction times between 0.5 and 20 h gave intermediate SP1. Best results were obtained when the extraction was per- results. In an example of reaction 5.5 g of SP2 (11.8 mmol) and formed in a Soxhlet extractor overnight. Aer evaporation of the 3.6 g of boric acid (58.2 mmol) were dissolved in 22.8 ml of 98% cyclohexane, 0.2 g of SP1 were obtained (6% recovered), which sulfuric acid. Following 51.0 ml of 65% SO3 fuming sulfuric acid can be used again in a new reaction. The solid residue that (0.8 mol of SO3) were added and allowed to react for 3 h. Aer remained aer the extraction with cyclohexane, corresponding quenching with water, NMR analysis of the mixture showed ca. to the sodium salt of MC1, was suspended in a biphasic mixture 8% of SP2, 35% of MC2, 46% of DC2 and 5% of TC2. Finally, aer of 30 ml of water and 30 ml of Et2O. Aer acidication to ca. pH the process of separation described above for the para-isomers, 2 with 10% aqueous H2SO4, MC1 was extracted to the organic 1.8 g of MC2 (35% yield) and 2.1 g of DC2 (43% yield) were iso- phase in its acid form. Aer decantation, the aqueous phase was lated as white solids. further extracted 2 times with 30 ml of Et2O. The organic layers Data for MC2. 31P{1H} NMR (101.27 MHz, CDCl3), d (ppm): were dried over MgSO4 and nally the solvent was vacuum 4.93 (s). 1H NMR (400.13 MHz, CDCl3), d (ppm): 8.14 (m, 1H, evaporated to give 1.40 g (42% yield) of the carboxylic phos- HC4{C6H4CO2H}); 8.10 (d, 1H, HC2{C6H4CO2H}, 3JHP ¼ 8.7 Hz); phine (MC1), as white solid, in purity above 95%. 7.65 (d, 2H, HC4{C6H4CF3}, 3JHH ¼ 7.7 Hz); 7.60 (d, 2H, HC2{- Data for MC1. 31P{1H} NMR (101.27 MHz, CDCl3), d (ppm): C6H4CF3}, 3JHP ¼ 7.9 Hz); 7.51 (m, 4H, HC5{C6H4CF3}-HC5{C6- 5.27 (s). 1H NMR (400.13 MHz, CDCl3), d (ppm): 8.10 (dd, 2H, H4CO2H}- HC6{C6H4CO2H}); 7.44 (pseudo-t, 2H, HC6{C6H4CF3}, HC3{C6H4CO2H}, 3JHH ¼ 8.5 Hz, 4JHP ¼ 1.5 Hz); 7.63 (d, 4H, 3 JHH ¼ 3JHP ¼ 7.1 Hz). 13C{1H} NMR (100.61 MHz, CDCl3), HC3{C6H4CF3}, 3JHH ¼ 8.0 Hz); 7.41 (m, 6H, HC2{C6H4CO2H}– d (ppm): 171.4 (s, CO2H); 138.8 (d, C6{C6H4CO2H}, 2JCP ¼ 17.2 HC2{C6H4CF3}). 13C{1H} NMR (100.61 MHz, CDCl3), d (ppm): Hz); 137.4 (d, C1{C6H4CF3}, 1JCP ¼ 14.0 Hz); 136.8 (d, 171.7 (s, CO2H); 142.77 (d, C1{C6H4CO2H}, 1JCP ¼ 14.4 Hz); 140.4 C6{C6H4CF3}, 2JCP ¼ 16.1 Hz); 136.6 (d, C1{C6H4CO2H}, 1JCP ¼ (d, C1{C6H4CF3}, 1JCP ¼ 14.2 Hz); 134.20 (d, C2{C6H4CF3}, 2JCP ¼ 13.3 Hz); 135.5 (d, C2{C6H4CO2H}, 2JCP ¼ 23.9 Hz); 131.5 (qd, 20.2 Hz); 133.7 (d, C2{C6H4CO2H}, 2JCP ¼ 19.6 Hz); 131.7 (q, C3{C6H4CF3}, 2JCF ¼ 32.5 Hz, 3JCP ¼ 8.1 Hz); 131.4 (s, C4{C6H4CF3}, 2JCF ¼ 32.6 Hz); 130.5 (d, C3{C6H4CO2H}, 3JCP ¼ C4{C6H4CO2H}); 130.4 (dq, C2{C6H4CF3}, 2JCP ¼ 25.0 Hz, 3JCF ¼ 6.9 Hz); 130.2 (s, C4{C6H4CO2H}); 125.8 (dq, C3{C6H4CF3}, 3JCP ¼ 3.8 Hz); 130.15 (d, C3{C6H4CO2H}, 3JCP ¼ 7.7 Hz); 129.5 (d, 7.4 Hz, 3JCF ¼ 3.6 Hz); 125.5 (q, CF3, 1JCF ¼ 272.5 Hz). 19F{1H} C5{C6H4CF3}, 3JCP ¼ 5.6 Hz); 129.4 (d, C5{C6H4CO2H}, 3JCP ¼ 6.1 NMR (376.50 MHz, CDCl3), d (ppm): 62.27 (s). HR-MS (ESI m/ Hz); 126.4 (q, C4{C6H4CF3}, 3JCF ¼ 3.6 Hz); 124.0 (q, CF3, 1JCF ¼ z) [M–H]: calculated for [C21H12F6O2P] 441.0485; found 272.2 Hz). 19F{1H} NMR (235.39 MHz, CDCl3), d (ppm): 62.40 441.0486. Elemental analysis: calculated for C21H13F6O2P: C, (s). HR-MS (ESI m/z) [M–H]: calculated for [C21H12F6O2P] 57.03; H, 2.96; found: C, 57.40; H, 3.06. 441.0485; found 441.0489. Elemental analysis: calculated for Data for DC1. 31P{1H} NMR (101.27 MHz, CD3OD), d (ppm): C21H13F6O2P: C, 57.03; H, 2.96; found: C, 57.15; H, 3.02. 4.66 (s). 1H NMR (400.13 MHz, CD3OD), d (ppm): 8.0 (bd, 4H, Data for DC2. 31P{1H} NMR (161.98 MHz, CD3OD), d (ppm): HC3{C6H4CO2H}, 3JHH ¼ 8.3 Hz); 7.7 (d, 2H, HC3{C6H4CF3}, 3JHH 4.61 (s). 1H NMR (400.13 MHz, CD3OD), d (ppm): 8.07 (m, 2H, ¼ 8.1 Hz); 7.5 (pseudo-t, 2H, HC2{C6H4CF3}, 3JHH ¼ 3JHp ¼ 7.7 HC4{C6H4CO2H}); 7.98 (bd, 2H, HC2{C6H4CO2H}, 3JHP ¼ 8.0 Hz); Hz); 7.4 (bt, 2H, HC2{C6H4CO2H}, 3JHH ¼ 3JHP ¼ 7.7 Hz). 13C{1H} 7.70 (bd, 1H, HC4{C6H4CF3}, 3JHH ¼ 7.9 Hz); 7.59 (bt, 1H, © 2022 The Author(s). Published by the Royal Society of Chemistry RSC Adv., 2022, 12, 7103–7114 | 7111 RSC Advances Paper HC5{C6H4CF3}, 3JHP ¼ 7.7 Hz); 7.52 (m, 6H, HC2{C6H4CF3}– C2{C6H3(CF3)2}, 2JCP ¼ 19.8 Hz, 3JCF ¼ 3.3 Hz); 132.29 (qd, HC6{C6H4CF3}–HC5{C6H4CO2H}–HC6{C6H4CO2H}). 13 C{1H} C3{C6H3(CF3)2}, 2JCF ¼ 33.3 Hz, 3JCP ¼ 6.2 Hz); 131.95 (s, NMR (100.61 MHz, CD3OD), d (ppm): 169.08 (s, CO2H); 139.7 (d, C4{C6H4CO2H}); 131.71 (qd, C3{C6H4CF3}, 2JCF ¼ 32.5 Hz, 3JCP ¼ C6{C6H4CF3}, 2JCP ¼ 14.7 Hz); 139.0 (d, C6{C6H4CO2H}, 2JCP ¼ 8.4 Hz); 130.65 (dq, C2{C6H4CF3}, 2JCF ¼ 26.6 Hz); 130.45 (d, 19.3 Hz); 138.2 (d, C1{C6H4CF3}, 1JCP ¼ 17.9 Hz); 137.9 (d, C3{C6H4CO2H}, 3JCP ¼ 8.9 Hz); 129.84 (d, C5{C6H4CF3}, 3JCP ¼ C1{C6H4CO2H}, 1JCP ¼ 12.9 Hz); 135.8 (d, C2{C6H4CO2H}, 2JCP ¼ 5.8 Hz); 129.70 (d, C5{C6H4CO2H}, 3JCP ¼ 6.1 Hz); 126.97 (q, 21.9 Hz); 132.7 (d, C3{C6H4CO2H}, 3JCp ¼ 7.0 Hz); 132.2 (qd, C4{C6H4CF3}, 3JCF ¼ 3.7 Hz); 123.80 (q, CF3{C6H4CF3}, 1JCF ¼ C3{C6H4CF3}, 2JCF ¼ 32.2 Hz, 3JCP ¼ 7.2 Hz); 131.8 (s, 272.8 Hz); 123.36 (sept, C4{C6H3(CF3)2}, 3JCF ¼ 3.6 Hz); 123.15 C4{C6H4CO2H}); 130.9 (dq, C2{C6H4CF3}, 2JCP ¼ 22.4 Hz, 3JCF ¼ (q, CF3{C6H3(CF3)2}, 1JCF ¼ 272.9 Hz). 19F{1H} NMR (376.50 3.9 Hz); 130.7 (d, C5{C6H4CF3}, 3JCP ¼ 5.9 Hz); 130.2 (d, MHz, CDCl3), d (ppm): 62.88 (s, 3F, CF3{C6H4CF3}), 62.99 (s, C5{C6H4CO2H}, 3JCP ¼ 6.7 Hz); 127.06 (q, C4{C6H4CF3}, 3JCP ¼ 6F, CF3{C6H3(CF3)2}). HR-MS (ESI m/z) [M–H]: calculated for 3.7 Hz); 125.33 (q, CF3, 1JCF ¼ 272.2 Hz). 19F{1H} NMR (376.50 [C22H11F9O2P] 509.0358; found 509.0361. Elemental analysis: MHz, CD3OD), d (ppm): 62.07(s). HR-MS (ESI m/z) [M–H]: calculated for C22H12F9O2P: C, 51.78; H, 2.37; found: C, 51.45; calculated for [C21H13F3O4P] 417.0509; found 417.0512. H, 2.49. Elemental analysis: calculated for C21H14F3O4P: C, 60.30; H, Data for DC4. 31P{1H} NMR (161.98 MHz, acetone-d6), 3.37; found: C, 59.58; H, 3.34. d (ppm): 3.50 (s). 1H NMR (400.13 MHz, acetone-d6), d (ppm): Data for TC2. 31P{1H} NMR (101.27 MHz, CD3OD), d (ppm): 8.14 (d, 2H, HC4{C6H4CO2H}, 3JHH ¼ 6.8 Hz); 8.08 (m, 3H, 5.07 (s). 1H NMR (400.13 MHz, CD3OD), d (ppm): 8.06 (m, 3H, HC4{C6H3(CF3)2}–HC2{C6H4CO2H}); 7.91 (d, 2H, HC2{C6H3(- HC4); 7.98 (bd, 3H, HC2, 3JHP ¼ 8.1 Hz); 7.52 (m, 6H, HC5 + HC6). CF3)2}, 3JHP ¼ 6.0 Hz); 7.66 (m, 4H, HC5 + HC6{C6H4CO2H}). 13C 13 C{1H} NMR (100.61 MHz, CD3OD), d (ppm): 169.2 (s, CO2H); {1H} NMR (100.61 MHz, acetone-d6), d (ppm): 166.90 (s, CO2H); 140.0 (d, C6, 2JCP ¼ 19.0 Hz); 138.4 (d, C1, 1JCP ¼ 12.9 Hz); 135.8 142.34 (d, C1{C6H3(CF3)2}, 1JCP ¼ 19.2 Hz); 138.91 (d, (d, C2, 2JCP ¼ 21.9 Hz); 132.6 (d, C3, 3JCP ¼ 7.0 Hz); 131.6 (s, C4); C6{C6H4CO2H}, 2JCP ¼ 18.5 Hz); 136.43 (d, C1{C6H4CO2H}, 1JCP 130.2 (d, C5, 3JCP ¼ 6.5 Hz). HR-MS (ESI m/z) [M–H]: calcu- ¼ 12.8 Hz); 135.68 (d, C2{C6H4CO2H}, 2JCP ¼ 23.8 Hz); 134.14 lated for [C21H14O6P] 393.0533; found 393.0535. (bd, C2{C6H3(CF3)2}, 2JCP ¼ 20.5 Hz); 132.41 (qd, C3{C6H3(CF3)2}, 3-((3,5-Bis(triuoromethyl)phenyl)(3-(triuoromethyl) 2 JCF ¼ 33.4 Hz, 3JCP ¼ 5.8 Hz); 132.33 (d, C3{C6H4CO2H}, 3JCP ¼ phenyl)phosphanyl)benzoic acid (MC4) and 3,30 -((3,5- 7.6 Hz); 131.97 (s, C4{C6H4CO2H}); 130.46 (d, C5{C6H4CO2H}, bis(triuoromethyl)phenyl)-phosphanediyl)dibenzoic acid 3 JCP ¼ 6.6 Hz); 124.18 (q, CF3, 1JCF ¼ 272.6 Hz); 123.86 (sept, (DC4). The same procedure described for the hydrolysis of the C4{C6H3(CF3)2}, 3JCF ¼ 3.9 Hz). 19F{1H} NMR (376.50 MHz, triuoromethyl groups in the homoleptic phosphines SP1 and acetone-d6), d (ppm): 62.38 (s). HR-MS (ESI m/z) [M–H]: SP2 was followed for the heteroleptic phosphine SP4. In calculated for [C22H12F6O4P] 485.0383; found 485.0385. a typical experiment, a solution of 2.5 g of phosphine SP4 (4.7 Elemental analysis: calculated for C22H13F6O4P: C, 54.34; H, mmol) and 3.25 g of boric acid (52.6 mmol) in 30 ml of 98% 2.69; found: C, 54.25; H, 2.82. sulfuric acid was cooled down to 0  C in an ice bath. Following, 3-(Bis(3,5-bis(triuoromethyl)phenyl)phosphanyl)benzoic 37 ml of 65% SO3 fuming sulfuric acid (0.6 mol of SO3) were acid (MC5). Following the same procedure as reported for the added dropwise and the mixture was allowed to react for 18.5 h monocarboxylic phosphines MC1 and MC2, 2.6 g of the tri- at room temperature. The mixture was then quenched on 180 g uoromethylated phosphine SP5 (4.3 mmol) and 1.30 g of boric of deoxygenated ice and extracted three times with 100 ml of acid (21 mmol) were dissolved in 24 ml of sulfuric acid resulting Et2O. Biphasic extractions at pH 6.7 allows the separation of the in the formation of an orange solution. The mixture was cooled oxide of phosphine DC4 in the aqueous phase while the dicar- in an ice bath and 28 ml of 65% SO3 fuming sulfuric acid boxylic phosphine DC4 is extracted pH 8.5. The monocarboxylic (0.46 mol of SO3) were added dropwise. Aer the complete phosphine MC4 is puried as reported for phosphines MC1 and addition of oleum, the dark mixture was stirred at room MC2. Aer full separation and purication, 0.67 g of DC4 (28% temperature for 62 h before being poured on 150 g of deoxy- yield) and 0.70 g of MC4 30% yield) were obtained as white genated ice. The resulting slurry was extracted 4 times with solids. 50 ml of Et2O. The organic solvent was evaporated giving a white Data for MC4. 31P{1H} NMR (161.98 MHz, CDCl3), d (ppm): solid. At this point, 31P{1H} NMR analysis showed a composi- 4.4 (s). 1H NMR (400.13 MHz, CDCl3), d (ppm): 8.17 (d, 1H, tion of ca. 65% of MC5 and 35% of phosphine oxides. Small HC4{C6H4CO2H}, 3JHH ¼ 7.4 Hz); 8.12 (d, 1H, HC2{C6H4CO2H}, amount of the starting phosphine SP5 were also detected by 3 JHP ¼ 8.1 Hz); 7.88 (s, 1H, HC4{C6H3(CF3)2}); 7.70 (m, 3H, TLC in silica (CH2Cl2). Therefore, the solid was treated with HC2{C6H3(CF3)2}-HC4{C6H4CF3}); 7.63 (d, 1H, HC2{C6H4CF3}, NaOH (5% in methanol) until neutralisation of the carboxylic 3 JHP ¼ 8.3 Hz); 7.55 (m, 2H, HC5{C6H4CO2H}–HC5{C6H4CF3}); groups. Following, the solvent was vacuum evaporated and the 7.50 (pseudo-t, 1H, HC6{C6H4CO2H}, 3JHH ¼ 3JHP ¼ 7.5 Hz); 7.44 SP5 was extracted from the solid with cyclohexane (Soxhlet (pseudo-t, 1H, HC6{C6H4CF3}, 3JHH ¼ 3JHP ¼ 7.3 Hz). 13C{1H} extractor, overnight). The solid residue containing the carbox- NMR (100.61 MHz, CDCl3), d (ppm): 170.95 (s, CO2H); 140.22 (d, ylic phosphine was mixed with 20 ml of water and 20 ml of C1{C6H3(CF3)2}, 1JCP ¼ 18.2 Hz); 138.72 (d, C6{C6H4CO2H}, 2JCP diethyl ether and the pH was brought to 5–6. The two phases ¼ 17.0 Hz); 136.72 (bd, C1{C6H4CF3}, 2JCP ¼ 15.9 Hz); 136.25 (d, were then decanted and the aqueous phase was extracted with 2 C1{C6H4CF3}, 1JCP ¼ 13.8 Hz); 135.68 (d, C2{C6H4CO2H}, 2JCP ¼ portions of 20 ml of Et2O. The organic layers were dried over 25.3 Hz); 135.32 (d, C1{C6H4CO2H}, 1JCP ¼ 12.9 Hz); 133.20 (bdq, MgSO4 and the solvent was vacuum evaporated to afford 0.88 g 7112 | RSC Adv., 2022, 12, 7103–7114 © 2022 The Author(s). Published by the Royal Society of Chemistry Paper RSC Advances of the carboxylic phosphine MC5 (35% yield). 31P{1H} NMR 4 (a) A. J. Nuñez, L. N. Shear, N. Dahal, I. A. Ibarra, J. Yoon, (161.98 MHz, CDCl3, at 323 K), d (ppm): 3.49 (s). 1H NMR Y. K. Hwang, J. S. Chang and S. M. Humphrey, Chem. (400.13 MHz, CDCl3, at 323 K), d (ppm): 8.22 (d, 1H, HC4{C6- Commun., 2011, 47, 11855–11857; (b) A. J. Nuñez, H4CO2H}, 3JHH ¼ 7.3 Hz); 8.14 (d, 1H, HC2{C6H4CO2H}, 3JHP ¼ M. S. Chang, I. A. Ibarra and S. M. Humphrey, Inorg. 8.5 Hz); 7.93 (s, 2H, HC4{C6H3(CF3)2}); 7.73 (d, 4H, HC2{C6H3(- Chem., 2014, 53, 282–288; (c) J. Václavı́k, M. Servalli, CF3)2}, 3JHP ¼ 6.6 Hz); 7.59 (bt, 1H, HC5{C6H4CO2H}, 3JHH ¼ 7.3 C. Lothschütz, J. Szlachetko, M. Ranocchiari and J. A. van Hz); 7.52 (bt, 1H, HC6{C6H4CO2H}, 3JHH ¼ 3JHP ¼ 7.3 Hz). 13C Bokhoven, ChemCatChem, 2013, 5, 692–696; (d) {1H} NMR (100.61 MHz, CDCl3, at 323 K), d (ppm): 170.31(s, A. A. Bezrukov, K. W. Törnroos and P. D. C. Dietzel, Cryst. CO2H); 139.17 (d, C1{C6H3(CF3)2}, 1JCP ¼ 18.3 Hz); 138.66 (d, Growth Des., 2017, 17, 3257–3266. C6{C6H4CO2H}, 2JCP ¼ 17.1 Hz); 135.83 (d, C2{C6H4CO2H}, 2JCP 5 (a) V. Ravindar, H. Hemling, H. Schumann and J. Blum, ¼ 26.0 Hz); 134.40 (d, C1{C6H4CO2H}, 1JCP ¼ 13.1 Hz); 133.31 Synth. Commun., 1992, 22, 841–851; (b) V. Ravindar, (bd, C2{C6H3(CF3)2}, 2JCP ¼ 20.5 Hz); 132.86 (qd, C3{C6H3(CF3)2}, H. Hemling, H. Schumann and J. Blum, Synth. Commun., 2 JCF ¼ 33.6 Hz, 3JCP ¼ 6.3 Hz); 132.50 (s, C4{C6H4CO2H}); 130.85 1992, 22, 1453–1459. (d, C3{C6H4CO2H}, 3JCP ¼ 8.7 Hz); 130.05 (d, C5{C6H4CO2H}, 3JCP 6 (a) M. M. Rauhut, I. Hechenbleikner, H. A. Currier, ¼ 6.3 Hz); 123.91 (sept, C4{C6H3(CF3)2}, 3JCF ¼ 3.7 Hz); 123.10 (q, F. C. Schaefer and V. P. Wystrach, J. Am. Chem. Soc., 1959, CF3, 1JCF ¼ 273.8 Hz). 19F{1H} NMR (376.50 MHz, CDCl3, at 323 81, 1103–1107; (b) J. A. Burns, J. C. Butler, J. Moran and K), d (ppm): 63.36 (s). HR-MS (ESI m/z) [M–H]: calculated for G. M. Whitesides, J. Org. Chem., 1991, 56, 2648–2650. [C23H10F12O2P] 577.0232; found 577.0251. Elemental analysis: 7 O. Herd, A. Heßler, M. Hingst, M. Tepper and O. Stelzer, J. calculated for C23H11F12O2P: C, 47.77; H, 1.96; found: C, 47.40; Organomet. Chem., 1996, 522, 69–76. H, 1.97. 8 J. H. Simons and E. O. Ramler, J. Am. Chem. Soc., 1943, 65, 389–392. X-ray crystallography 9 H. Gilman and D. Blume, J. Am. Chem. Soc., 1943, 65, 2467– 2468. 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