INTRODUCTION

Boron cluster anions are widely used as components of photovoltaic devices [1–6], catalysts [7, 8], biosensors [9, 10], and molecular magnets [11, 12]. One of the most important areas of application of closo-borate anions is boron neutron capture therapy of malignant tumors [13–18].

The main interest of researchers is focused on the development of methods for the directed functionalization of boron cluster anions. Thus, along with the processes of electrophilic [19–21] and nucleophilic substitution [22, 23] of hydrogen atoms in the boron cluster, the process of ipso-substitution [24–26] can be considered as an effective method of functionalization.

Halonium ions are one of the types of such groups, which can react with a number of nucleophilic reagents. This approach was successfully extended to iodonium derivatives of carboranes [27], which react with various nucleophiles with selective substitution of the arylgalonium substituent. Monocarboranes and boron cluster anions have a negative charge, and aryliodonium zwitterions based on them differ from derivatives of neutral carboranes in terms of reactivity and selectivity of the processes. The preparation of derivatives of hypervalent iodine through the oxidation of iodo-closo-borates is described in the literature [28]. It should be noted that this approach has a number of disadvantages, since it leads to the formation of oxidation products of the cluster fragment. The use of hypervalent iodine compounds can significantly increase the yield of target closo-borates [29, 30]. Iodonium derivatives can enter into substitution reactions of PhI groups with a number of nucleophiles (pyridines, thioureas, cyanide ion, azide ion, etc.) [31–35]. In [36, 37], the possibility of using phenyliodonium derivatives of the closo-dodecaborate anion and substituted analogs for the targeted introduction of various functional groups into the cluster was shown.

Thus, the use of iodonium functional substituents as leaving (ipso) groups is a rather powerful tool for creating new boron-containing compounds with a given set of properties. In this regard, the aim of this work was the creation of new substituted derivatives of the closo-dodecaborate anion and natural amino acids based on the processes of nucleophilic substitution in the [B12H11IPh]– anion.

EXPERIMENTAL

Elemental analysis for carbon, hydrogen, and nitrogen was performed on a CHNS-3 FA 1108 Elemental Analyzer (Carlo Erba). Boron was determined by ICPMS on an iCAP 6300 Duo inductively coupled plasma atomic emission spectrometer at the Center for Collective Use of the Research Scientific Analytical Center of the IREA Federal State Unitary Enterprise (State Scientific-Research Institute of Chemical Reagents and High Furity Chemical Substances).

IR spectra of the synthesized compounds were recorded on an Infralum FT-08 IR Fourier spectrometer (NPF AP Lumex) in the range 4000–400 cm–1 with a resolution of 1 cm–1. Samples were prepared as potassium bromide pellets.

1H, 11B, and 13C NMR spectra of solutions of the investigated substances in CD3CN were recorded on a Bruker Avance II-300 spectrometer at frequencies of 300.3, 96.32, and 75.49 MHz, respectively, with internal deuterium stabilization. Tetramethylsilane or boron trifluoride etherate were used as external standards.

ESI mass spectra of solutions of the investigated substances in CH3CN were recorded on a Bruker MicrOTOF-Q spectrometer (Bruker Daltonik, Germany). Ionization conditions: Apollo II electrospray ionization source, ion spray voltage +(–)4500 V, temperature 200°C, flow 3 μL/min.

Tetraphenylphosphonium phenyliodododecaborate (Ph4P)[B12H11IPh]. Acetonitrile (15 mL) and trifluoroacetic acid (2 mL) were added to (Ph4P)2[B12H12] (2.0 g, 2.4 mmol). PhI(OAc)2 (0.77 g, 2.4 mmol) was added to the resulting solution, and the reaction mixture was stirred in an atmosphere of dry argon with moderate heating (up to 40°C) for 2 h. After that, the solution was concentrated on a rotary evaporator and the product was recrystallized from a mixture of acetonitrile and diethyl ether. The resulting solid was washed with glacial acetic acid and diethyl ether, then dried under oil pump vacuum. Yield, 1.45 g (88%).

11B NMR (CD3CN, ppm): –12.1 (s, 1B, B–I); ‒15.5 (m, 11B, B–H); 1H NMR (CD3CN, ppm): 7.98, 7.74, 7.65 (20H, aromat., Ph4P); 7.76, 7.38, 7.15 (m, 5H, aromat., C6H5I); 2.25–0.15 (br m, 11H, B–H).

Derivative of glycine ethyl ester (Ph4P)[B12H11NH2CH2COOEt]. A mixture of (NH2CH2COOEt)·HCl (0.47 g, 3.4 mmol) and 4‑dimethylaminopyridine (0.43 g, 3.4 mmol) in anhydrous tetrahydrofuran (THF, 20 mL) was prepared. The resulting suspension was stirred in a dry argon atmosphere at room temperature until complete precipitation of dimethylaminopyridinium hydrochloride (~0.5 h). The precipitate was filtered off, and (Ph4P)[B12H11IPh] (0.50 g, 0.7 mmol) was added to the mother solution. The resulting reaction mass was heated at 80°C for 4 h in a dry argon atmosphere. After the completion of the reaction, the resulting solution was evaporated on a rotary evaporator, and the solid residue was recrystallized from a mixture of methanol and diethyl ether. The resulting powder was dissolved in dichloromethane and washed with a 0.1 M HCl solution. The organic phase was separated, washed with water until neutral pH, dried over anhydrous sodium sulfate, and then concentrated on a rotary evaporator. The product was dried under vacuum. Yield, 0.29 g (70%).

IR (KBr, cm–1, selected bands): 3320, 3258 (ν(N–H)); 2485 (ν(B–H)); 1745 (ν(C=O)); 1042 (δ(B–B–H)). 11B NMR (CD3CN, ppm): –7.7 (s, 1B, B–N); ‒16.5 (m, 11B, B–H); 1H NMR (CD3CN, ppm): 7.96, 7.75, 7.71 (20H, aromat., Ph4P); 6.86 (br s, 2Н, NH2); 4.28 (q, 2H, COO–CH2–CH3, J = 7 Hz); 3.99 (d, 2H, CH2COO, J = 6 Hz); 1.29 (t, 3H, COO–CH2–CH3, J = 7 Hz); 2.20–0.16 (br m, 11H, B–H). 13C NMR (CD3CN, ppm): 171.0 (COO); 135.4, 134.7, 130.3, 118.3 (Ph4P); 61.5 (COO–CH2–CH3); 45.4 (CH2–COO); 14.5 (COO–CH2–CH3). MS(ESI)–: m/z = 285.2 ([B12H11NH2CH2COOEt]{CH3CN}–).

Phenylalanine ethyl ester derivative (Ph4P)[B12H11NH2CH(CH2C6H5)COOEt] was obtained by a similar method. A mixture of PhCH2CH(NH2)COOEt·HCl (0.83 g, 3.6 mmol) and 4-dimethylaminopyridine (0.44 g, 3.6 mmol) in anhydrous THF (20 mL) was prepared. The resulting suspension was stirred in a dry argon atmosphere at room temperature until complete reprecipitation of dimethylaminopyridinium hydrochloride (~0.5 h). Then the precipitate was filtered off, and (Ph4P)[B12H11IPh] (0.50 g, 0.7 mmol) was added to the mother solution. The flask was purged with argon, the resulting reaction mass was heated with stirring to 80°C for 4 h. After the completion of the reaction, the resulting solution was evaporated on a rotary evaporator, and the solid residue was recrystallized from a mixture of methanol and diethyl ether. The resulting crude product was dissolved in dichloromethane and washed with 0.1 M HCl solution. The organic phase was separated, washed with water until neutral pH, dried over anhydrous sodium sulfate, and concentrated on a rotary evaporator. The product was dried under vacuum. Yield, 0.33 g (75%).

IR (KBr, cm–1, selected bands): 3301, 3240 (ν(N–H)); 2470 (ν(B–H)); 1750 (ν(C=O)); 1055 (δ(B–B–H)). 11B NMR (CD3CN, ppm): –7.2 (s, 1B, B–N); –16.8 (br m, 11B, B–H). 1H NMR (CD3CN, ppm): 7.95, 7.76, 7.69 (20H, aromat., Ph4P); 7.45–7.25 (m, 5H, CH2–C6H5); 6.86 (br s, 2Н, NH2); 4.36 (m, 1H, NH–CH–COO), 4.28 (q, 2H, COO–CH2–CH3, J = 7 Hz); 3.33 (d, 2H, CH2–C6H5, J = 7 Hz), 1.28 (t, 3H, COO–CH2–CH3, J = 7 Hz), 1.90–0.10 (br m, 11H, B–H). 13C NMR (CD3CN, ppm): 170.9 (COO), 135.2, 134.5, 130.0, 118.4 (Ph4P); 137.1, 130.9, 129.6, 128.1 (–CH2–Ph), 62.7 (COO–CH2–CH3), 56.8 (CH–COO), 40.1 (CH–CH2–Ph), 14.5 (COO–CH2–CH3). MS(ESI)–: m/z = 334.1 ([B12H11NH2CHCH2C6H5COOEt]–).

RESULTS AND DISCUSSION

The synthesis of phenyliodonium derivative of the closo-dodecaborate anion in anhydrous medium is proposed. The reaction of the [B12H12]2– anion with PhI(OAc)2 was carried out in a mixture of acetonitrile and trifluoroacetic acid (Fig. 1). The reaction progress was monitored on the basis of 11B NMR spectroscopy data. Thus, the 11В NMR spectrum of salts of the [B12H11IPh]– anion is represented by two signals: δ1 = –12.5 ppm and δ2 = –15.6 ppm with an integrated intensity ratio of 1 : 11. The structure of the substituent in the derivative was determined using 1H NMR spectroscopy. Thus, in the spectrum of compound (PBu4)[B12H11IPh], along with the signals of protons from the tetrabutylammonium cation, signals at 7.76, 7.39, and 7.16 ppm are observed in the region of aromatic protons (m, 5H, aromat., C6H5I), which corresponds to the phenyl substituent at the iodine atom. In addition, the spectrum contains signals from hydrogen atoms bound to the boron cage. They appear as a broadened multiplet in the range 2.20–0.16 (br m, 11H, B–H).

Fig. 1.
figure 1

Synthesis of substituted ammonio-closo-dodecaborates based on amino acid esters.

Full size image

In the second stage, derivatives based on esters of amino acids were obtained, which were used as nucleophilic reagents.

Since the amino acid esters in the form of free bases are unstable, we used the corresponding hydrochlorides. In this case, the deprotonated forms of esters were obtained in situ under the action of organic bases in the medium of tetrahydrofuran (THF). The use of triethylamine as a base led to the formation of a significant amount of the chlorination byproduct of the closo-dodecaborate anion, which is obviously related to the solubility of the hydrochloride in THF. Therefore, we decided to use 4-dimethylaminopyridine as a base; its hydrochloride is easily removed from the reaction mixture by filtration.

The addition of the ester of (Ph4P)[B12H11IPh] to the solution results in the substitution of the phenyliodonium group for the amino acid residue. The reaction takes place already at room temperature, but the rate of this process is low. Heating the reaction mixture to 80°C makes it possible to achieve complete conversion of the initial iodonium derivative in 4 h. It should be noted that the studied process is sensitive to the presence of water and chloride ions in the system, which leads to side processes and reduces the yield of the target product.

The reaction progress was monitored on the basis of 11B NMR spectroscopy data. Thus, the 11B NMR spectra of the target ammonium-type derivatives contain two signals in the range –7.2…–7.7 ppm (s, 1B, B–N) and –16.5…–16.8 ppm (m, 11B, B–H). The introduction of a more electronegative ammonium group leads to a shift of the signal from the substituted boron atom to a weaker field as compared to the spectrum of the initial iodonium derivative.

The structure of functional groups in the obtained products was determined using 1H and 13C NMR spectroscopy. Thus, in the 1H NMR spectrum of compound (Ph4P)[B12H11NH2CH2COOEt] along with the signals of the cation protons, the signals of the protons of the amino acid residue are observed. The ammonium group is represented by a broadened singlet at 6.86 ppm (2H, NH2), the protons of the methylene group appear as a doublet at 3.99 ppm (2H, CH2COO, J = 6 Hz). This signal splitting is typical of amino acid derivatives with a rigid spatial structure [38]. The 13C NMR spectrum of compound (Ph4P)[B12H11CH2COOEt] shows signals of carbon atoms of the carbonyl group at 171.0 ppm and a methylene group at 45.4 ppm. In the IR spectrum of this compound, absorption bands of stretching vibrations of the N–H bond appear at 3320 and 3258 cm–1, absorption bands of stretching vibrations of the C=O bond are observed at 1745 cm–1, and the absorption bands of the phenyliodonium fragment disappear. Replacement of the exopolyhedral substituent has little effect on the position and shape of the band of stretching vibrations of the boron–hydrogen bond.

In addition, the formation of the target compounds was confirmed by ESI-mass spectrometry. Thus, in the anionic part of the mass spectra of the products, there are intense peaks of ions {[B12H11NH2CH2COOEt]·CH3CN}– at 285.2 amu for (Ph4P)[B12H11NH2CH(CH2C6H5)COOEt] and ions [B12H11NH2CHCH2C6H5COOEt]– at 334.1 amu for compound (Ph4P)[B12H11NH2CH2COOtBu].

CONCLUSIONS

A method for the synthesis of the [B12H11IPh]– anion in an anhydrous medium has been proposed. New substituted ammonium-type closo-dodecaborates [B12H11NH2CHRCOOEt]– (R = H, CH2Ph) were obtained based on the processes of nucleophilic substitution of the phenyliodonium substituent under the action of ethyl esters of amino acids.