Synthesis and characterization of tetraphenylammonium salts

The phenyl (Ph) group is a representative substituent in the field of organic chemistry as benzene (the parent molecule) is of fundamental importance. Simple Ph-substituted compounds of common chemical elements are well known. However, extensive structural characterization of tetraphenylammonium (Ph4N+) salts has not been reported. Herein, the synthesis of Ph4N+ salts and their characterization data including the 1H and 13C nuclear magnetic resonance (NMR) spectra and the single-crystal X-ray structure have been presented. An intermolecular radical coupling reaction between an aryl radical and a triarylammoniumyl radical cation was conducted to synthesize the target moieties. The Ph4N+ salts described herein are the simplest tetraarylammonium (Ar4N+) salts known. The results reported herein can potentially help access the otherwise inaccessible non-bridged Ar4N+ salts, a new class of rigid and sterically hindered organic cations.


Introduction
The elements in groups 13 (B and Al), 14 (C and Si), and 15 (N and P) typically form tetrahedral ions or molecules of the general formula R 4 Z 0 ± 1 , when four identical substituents (R 4 ) are attached to the central element (Z). The charge on the atom Z depends on the group to which it belongs: −1, 0, and +1 for groups 13, 14, and 15, respectively. Compounds of type R 4 Z 0 ± 1 , bearing simple R substituents, are of special importance and considered benchmark compounds. The structural features, physical properties, and chemical reactivities of the other derivatives belonging to this class of compounds were compared with those of the benchmark compounds for a deeper understanding of the compound characteristics.
Therefore, for a long time, organic chemists have focused on synthesizing such R 4 Z 0 ± 1 compounds bearing simple R substituents. The compounds of the general formula R 4 Z 0 ± 1 (R = Ph (Ph 4 B − , Ph 4 Al − , Ph 4 C, Ph 4 Si, and Ph 4 P + ; Fig. 1)) 1-6 are known since long. Ph 4 Si was identi ed more than 130 years ago.
The fundamental properties of these Ph 4 Z 0 ± 1 compounds have been studied extensively over a long period of time. The results serve as references during the study of the corresponding tetraaryl-substituted compounds (Ar 4 Z 0 ± 1 ). Quantum chemical calculations have been conducted for Ph 4 N + . 7 However, the experimental properties of this simple organic cation remain largely unknown. Though several researchers have reported the application prospects of the Ph 4 N + salts (Supplementary Table 1), the synthetic route followed, and the compound characteristics have not been reported.
It has been reported that the pentatritiated tetraphenylammonium salts (1; Fig. 2a) can be formed following the nuclear-chemical method via the tritium b-decay of hexatritiated benzene (C 6 T 6 ). 8, 9 The isomorphic co-crystallization data and the radioactivity-based yields have been documented. However, the detailed synthetic procedure and data from experiments conducted for structure identi cation have not been reported. Bridged Ar 4 N + salts are structurally similar to the Ph 4 N + salts. In 1963, Nesmeyanov synthesized the (N,N-diphenyl)carbazolium salts (2; Fig. 2b) as the rst examples of this class of compounds. 10 The key reaction step affording 2 from precursor 3 was the intramolecular N-arylation of triarylamine. The step proceeded via the decomposition of the spatially proximal aryldiazonium moiety. This process resulted in the formation of a 5-membered ring containing a nitrogen atom bearing four aromatic rings. Following the success of the method, a similar cyclization strategy was followed for the synthesis of various (N,N-diaryl)carbazolium salts [11][12][13][14][15][16] (such as 4 and 5; Fig. 2c), and sul de-or amidebridged Ar 4 N + salts (6 17 and 7 18 , respectively). Recently, the quaternary ammonium structure of 2 was con rmed using the single-crystal X-ray diffraction technique. 13,16 However, none of these bridged Ar 4 N + salts could be converted to Ph 4 N + salts, as there is a dearth of e cient methods that can be used to remove the bridge moieties. 17 Ar 4 N + is a promising organic cation that can be used for developing surfactants, supporting electrolytes, phase-transfer catalysts, and anion-exchange membranes. 13 Also, it is potentially useful for industrial and biological studies. The wide application range of the cation can be attributed to the high chemical stability 14,15 and unique rigid structure of the organic cation. Although the bridged Ar 4 N + cations represented by 2 have been studied and characterized, non-bridged Ar 4 N + cations have not been explored because of synthetic limitations. Herein, we report a novel synthetic strategy for the preparation of Ph 4 N + salts. This is the rst report where the results of structural characteristics of the cation have been reported.

Results And Discussion
Synthetic strategy. The direct N-phenylation of triphenylamine (8; Fig. 3a) using a Ph cation (or its synthetic equivalent) to form Ph 4 N + is di cult because 8 is weakly nucleophilic (indicated by the low pK aH value (-3.91) 19 recorded during N-protonation). Ph 4 N + salts could not be obtained by reacting 8 with a phenyldiazonium unit. 10 The N-phenylation of 8 using diphenyliodonium 20 or the in-situ-generated benzyne 21 unit was also unsuccessful. We designed the triarylammoniumyl salt (9; Fig. 3b) as a novel precursor that could be used for the synthesis of Ph 4 N + to address the problem of low reactivity of 8. In general, triarylamines can be oxidized to form the corresponding radical cations (referred to as triarylammoniumyls) that exhibit high reactivity. Triphenylammoniumyl easily dimerizes via the para positions of the Ph groups following the process of intermolecular radical coupling to afford tetraphenylbenzidine. 22 The results obtained from quantum chemical calculations revealed that the singly occupied molecular orbital of triphenylammoniumyl was spread over all the Ph rings and the central nitrogen atom. 23 Therefore, we expected that the intermolecular radical coupling reaction involving a triphenylammoniumyl unit and an aryl radical occurs via the nitrogen atom if the Ph group is hindered by steric protection. The tert-butyl and bromo groups were selected as the bulky protecting groups of 9 at the metaand para-positions, respectively. These groups can exert a large extent of steric hindrance and can be removed at the later stages of the synthetic procedure.
Synthesis. The starting material used for the synthesis of the target was tris[(3,5-di-tertbutyl)phenyl]amine (10; Fig. 4), which was prepared over three steps starting from benzene: Friedel-Crafts reaction, dealkylative bromination, and palladium-catalyzed amination. 24,25 The para-brominated compound 11 was formed in 81% yield when 10 was treated with N-bromosuccinimide (NBS). The triarylamine 11 was then activated to form the triarylammoniumyl salt 9 following the one-electron oxidation process using AgBF 4 . 26 It was isolated as a monohydrate in 93% yield. Similar to other triarylammoniumyl salts, 22 9 was a blue solid. The color could be attributed to the absorption over the visible region (l max = 797 nm in o-dichlorobenzene). Following this, we investigated the key intermolecular radical coupling reactions. Bis(3,5-di-tert-butyl)benzoyl peroxide (13) was used as the starting material for the in situ generation of the (3,5-di-tert-butyl)phenyl radical (12). The formation of the radical proceeded via the process of O-O homolysis, which was followed by the process of decarboxylation. 27 A mixture of 9 and 13 was heated to 120 ℃ in o-dichlorobenzene in the presence of (2,6-di-tert-butyl)pyridine (14; used as a base) until the characteristic blue color of 9 disappeared. The reaction conditions were selected from the results of the screening experiments (vide infra). The desired Ar 4 N + salt 15 was successfully formed in a low yield (0.1%), which was then isolated using the normal-phase ion-pair chromatography technique. 28 Under these conditions, 4 g of 9 could be converted to 5 mg of 15. The byproducts formed during the reaction were triarylamine 11 (11%), solvent adduct 16 (4% based on 13), and sterically congested triarylamines 17 (7%) and 18 (8%) possessing ortho-[(3,5-di-tert-butyl)benzoyl]oxy and ortho-(3,5-di-tert-butyl)phenyl groups, respectively. The structures of 17 and 18 were determined using the single-crystal X-ray diffraction technique (Supplementary Tables 2 and 3, respectively). The formation of 17 and 18 indicated that the extent of steric protection provided by the meta-tert-butyl groups in 9 was not su cient to e ciently inhibit the occurrence of the ortho-substitution reactions at the Ph rings. Supplementary Table 4 shows the process of reaction condition screening for the intermolecular radical coupling reaction conducted on a small scale using 9 (80-100 mg). When the reaction was conducted in o-dichlorobenzene in the presence of 14 (entry 1), the yield of the desired ammonium salt 15 was 0.12% (determined by 1 H-NMR spectroscopic analysis). Although the same yield (0.12%, entry 2) of 15 was obtained when the reaction was carried out in the absence of 14, it was di cult to purify the product under these conditions as various byproducts were also formed during the process. The use of other solvents in combination with 14 afforded lower (entries 3-10) or undetectable (entries 11-14) yields of 15, and a complex mixture of compounds which could not be puri ed or analyzed (entries 16-21). Thus, the reaction conditions presented in entry 1 were used to synthesize 15 from 9 (4 g). We also attempted the intermolecular radical coupling reaction involving 13 and tris[(3,5-di-tert-butyl)phenyl]ammoniumyl BF 4 − (19; devoid of the p-bromo groups). The latter was prepared following the one-electron oxidation of 10. However, the desired product tetrakis[(3,5-di-tert-butyl)phenyl]ammonium BF 4 − (20) could not be isolated as the reaction yielded a complex mixture. Therefore, the removal of all the bromo groups in 15 was carried out following the process of bromine-lithium exchange using n BuLi at − 78°C. The resulting product was protonated with (2,6-di-tert-butyl)pyridinium BF 4 − salt (21), affording 20 in 90% yield. Since we selected diacyl peroxide 13 as the precursor of aryl radical 12 to introduce the (3,5-di-tert-butyl)phenyl group in 9, the ammonium nitrogen of 20 was connected to four identical aryl groups. The counter anion of 20 was exchanged to prepare the corresponding B(C 6 F 5 ) 4 − salt (22), the structure of which was con rmed using the single-crystal X-ray diffraction technique (Supplementary Table 5). The nal step toward the formation of Ph 4 N + involved the dealkylation of the tert-butyl groups present on the aromatic rings of 20. All the eight tert-butyl groups could be successfully removed when 20 was heated at 150 ℃ over a period of 14 h in a solvent amount of tri uoromethanesulfonic acid (TfOH). 29  Single-crystal X-ray structure analysis. The single-crystal X-ray diffraction technique was used to analyze the structure of 24. Analysis of the results proved the quaternary ammonium structure of 24 (Fig. 5c, top view). The counter anion B(C 6 F 5 ) 4 − was omitted for clarity (Supplementary Table 6). The Ph 4 N + structure exhibited S 4 -like symmetry and not D 2d -like symmetry. The result agreed well with the theoretically predicted result. 32 The N-C(sp 2 ) bond length in 24 (present between the Ph 4 N + nitrogen unit and the sp 2 carbon atom) in the Ph group was 1.529 ± 0.003 Å (Fig. 5c, side view). This bond is longer than the N-C(sp 2 ) bonds in (CH 3 ) 3 PhN + , (CH 3 ) 2 Ph 2 N + , (CH 3 )Ph 3 N + , and N,N-diphenylcarbazolium, which were 1.50, 33 1.51, 21 1.52, 21  these Ph 4 Z 0 ± 1 , re ecting the di culty faced during synthesis. The shortest distance between the orthohydrogen in the Ph unit and the ipso carbon in the adjacent Ph group in Ph 4 N + was 2.46 Å (Fig. 5c, side view). The Van der Waals radii for hydrogen (1.00 Å) and carbon (1.77 Å) indicate that steric repulsion is generated. 39 The corresponding H-C distances in Ph 4 C, Ph 4 B − , and Ph 4 P + were 2.54, 34 2.59, 35     (2) from precursor 3 following the process of intramolecular N-arylation. The bridge moiety indicated in blue must be removed to obtain the Ph 4 N + salts. c, Other bridged Ar 4 N + salts such as (N,Ndiphenyl)carbazolium salts (4) bearing various substituents Y on the aryl groups, spirobicarbazolium salts (5), sul de-bridged Ar 4 N + salts (6), and amide-bridged Ar 4 N + salts (7) prepared following the intramolecular N-arylation strategy. The bridge moieties are indicated in blue.

Figure 3
Synthetic strategy followed for the construction of a non-bridged Ar 4 N + structure. a, Direct N-phenylation of 8 with a Ph cation is di cult as the N atom is a weak nucleophile. b, Intermolecular radical coupling reaction between an aryl radical and the triarylammoniumyl salt 9 bearing bulky protecting groups that exert steric hindrance and block the reactions at the Ph groups.

Figure 4
Synthetic scheme for the formation of the Ph 4 N + salts 23 and 24. Triarylammoniumyl salt 9 was prepared from 10 over 2 steps. The intermolecular radical coupling reaction between 9 and aryl radical 12, formed in situ following the thermolysis of the diacyl peroxide 13, yielded the Ar 4 N + salt (15) along with various byproducts (11, 16, 17, and 18). Removal of the bromo and tert-butyl groups in 15 afforded 23, whose counter anion was exchanged to obtain 24.