Synthesis and Structural Characterization of Amidine, Amide, Urea and Isocyanate Derivatives of the Amino-closo-dodecaborate Anion [B12H11NH3]−

The synthesis and structural characterization of new derivatives of [B12H12]2− is of fundamental interest and is expected to allow for extended applications. Herein we report on the synthesis of a series of amidine, amide, urea and isocyanate derivatives based on the amino-closo-dodecaborate anion [B12H11NH3]−. Their structures have been confirmed by spectroscopic methods, and nine crystal structures are presented.

Since the isolation of 1 in 1960 [28], many routes to substituted closo-dodecaborate anions have been reported via the construction of B-N, B-O, B-S, B-Hal or B-C bonds [29], and the ammonium dodecaborate [B 12 H 11 NH 3 ] − (2) serves as one of the fundamental building blocks for further functionalization [30]. Monoanionic 2 can be synthesized from the reaction of 1 with hydroxylamine-O-sulfonic acid (H 2 N-SO 3 H) on a multi-gram scale [30][31][32]. The -NH 3 site can be deprotonated under basic conditions and then combined with acyl chlorides, carbodiimides or aldehydes to afford the corresponding amides 3 [33][34][35][36][37], guanidines 4 [34] and imines 5 [38]. Dodecaborate amidines 6 have not been explored yet, and urea derivatives 7 were unknown until we recently found that the reaction of 2 with dialkylcarbamoyl chlorides ClC(O)NMe 2 or ClC(O)NEt 2 affords the corresponding {B 12 }-substituted N,N-dialkyl ureas [39]. The isocyanate derivative 8 was originally synthesized from the reaction of the carbonyl derivative [B 12 H 11 (CO)] − with NaN 3 but characterized only by 11 B-NMR and IR spectroscopy [40]. Herein we present: (1) the synthesis of three new {B 12 }-based amidines 6 with two crystal structures; (2) six crystal structures of {B 12 }-based amides 3 and a simple approach for the interconversion between their dianionic and monoanionic forms; (3) the synthesis of two new {B 12 }-based aromatic ureas 7; (4) a new route to isocyanate 8 and its crystal structure.

Synthesis of {B 12 }-based Amidinium Ions
Amidine derivatives based on the {B 12 } cluster have not been reported before, and in the following, methods to synthesize them are presented. Combination of dimethyl formamide with 2,4,6-trimethylbenzoyl chloride afforded the chloroiminium intermediate, which upon attack by [B 12 H 11 NH 2 ] 2− afforded 6a (Scheme 1a). This reaction allowed for the isolation of the desired product; however, the yield of 40% was moderate, and furthermore extension of the substrate scope by this method did not appear convenient. Using a related strategy, we found that the carbonyl group of {B 12 }-based amides can be activated by pentafluorobenzoyl chloride, and subsequent attack by amines would then lead to {B 12 }-based amidinium ions (Scheme 1b). Following this approach, products 6b and 6c were isolated in excellent yields of 91% and 100%, respectively.

Synthesis of {B12}-based Amides
{B12}-based amides 3 were originally synthesized by other groups [33][34][35][36]. The products were isolated in their O-protonated form 3-H, and there was only one crystal structure reported, namely 3a-H with R = Ph (Scheme 2). Our group recently modified the reaction conditions, and the products were obtained in up to 95% yields in the O-deprotonated form 3 after chromatography on silica gel [36]. Our approach uses smaller amounts of acyl chlorides and a slight excess of sodium hydride base, which results in the isolation of the dianionic form (for this study, 3a-d were resynthesized according to [37] in order to probe their solid-state structures). Adjustment of the pH value with diluted hydrochloric acid during the work-up or after isolation leads to 3-H in their O-protonated form. Backconversion to 3 can be achieved by dissolution in MeCN, treatment with Et3N and distillation of all the volatiles. Pyridine-substituted 3e was synthesized as a new product. Since purification by chromatography proved difficult, it was isolated as 3e-H in 50% yield upon acidic work-up and recrystallization from methanol. Conversion to 3e occurred quantitatively using the abovementioned procedure. In contrast to previously described amides, protonation of 3e takes place at the pyridine ring, indicating the higher basicity of the heterocycle as compared to the amide moiety. The 11 B{ 1 H}-NMR spectra of 3b, 3b-H, 3e and 3e-H are shown in Figure S1 as representative examples to demonstrate the effect of protonation. For R = Ph (3a), 4-F-C6H4 (3b), 4-I-C6H4 (3c) 4-MeO-C6H4 (3d-H), 2-pyridyl (3e) and 2-pyridyl-H (3e-H), crystal structures were elucidated, and selected structural features are discussed below. Scheme 2. Synthesis of {B12}-based amides 3 and interconversion between their dianionic and monoanionic forms; compounds 3a-d were prepared according to [37].

Synthesis of {B 12 }-based Amides
{B 12 }-based amides 3 were originally synthesized by other groups [33][34][35][36]. The products were isolated in their O-protonated form 3-H, and there was only one crystal structure reported, namely 3a-H with R = Ph (Scheme 2). Our group recently modified the reaction conditions, and the products were obtained in up to 95% yields in the O-deprotonated form 3 after chromatography on silica gel [36]. Our approach uses smaller amounts of acyl chlorides and a slight excess of sodium hydride base, which results in the isolation of the dianionic form (for this study, 3a-d were resynthesized according to [37] in order to probe their solid-state structures). Adjustment of the pH value with diluted hydrochloric acid during the work-up or after isolation leads to 3-H in their O-protonated form. Back-conversion to 3 can be achieved by dissolution in MeCN, treatment with Et 3 N and distillation of all the volatiles. Pyridine-substituted 3e was synthesized as a new product. Since purification by chromatography proved difficult, it was isolated as 3e-H in 50% yield upon acidic work-up and recrystallization from methanol. Conversion to 3e occurred quantitatively using the above-mentioned procedure. In contrast to previously described amides, protonation of 3e takes place at the pyridine ring, indicating the higher basicity of the heterocycle as compared to the amide moiety. The 11 B{ 1 H}-NMR spectra of 3b, 3b-H, 3e and 3e-H are shown in Figure S1 as representative examples to demonstrate the effect of protonation. For R = Ph (3a), 4-F-C 6 H 4 (3b), 4-I-C 6 H 4 (3c) 4-MeO-C 6 H 4 (3d-H), 2-pyridyl (3e) and 2-pyridyl-H (3e-H), crystal structures were elucidated, and selected structural features are discussed below.

Synthesis of {B12}-based Amides
{B12}-based amides 3 were originally synthesized by other groups [33][34][35][36]. The products were isolated in their O-protonated form 3-H, and there was only one crystal structure reported, namely 3a-H with R = Ph (Scheme 2). Our group recently modified the reaction conditions, and the products were obtained in up to 95% yields in the O-deprotonated form 3 after chromatography on silica gel [36]. Our approach uses smaller amounts of acyl chlorides and a slight excess of sodium hydride base, which results in the isolation of the dianionic form (for this study, 3a-d were resynthesized according to [37] in order to probe their solid-state structures). Adjustment of the pH value with diluted hydrochloric acid during the work-up or after isolation leads to 3-H in their O-protonated form. Backconversion to 3 can be achieved by dissolution in MeCN, treatment with Et3N and distillation of all the volatiles. Pyridine-substituted 3e was synthesized as a new product. Since purification by chromatography proved difficult, it was isolated as 3e-H in 50% yield upon acidic work-up and recrystallization from methanol. Conversion to 3e occurred quantitatively using the abovementioned procedure. In contrast to previously described amides, protonation of 3e takes place at the pyridine ring, indicating the higher basicity of the heterocycle as compared to the amide moiety. The 11 B{ 1 H}-NMR spectra of 3b, 3b-H, 3e and 3e-H are shown in Figure S1 as representative examples to demonstrate the effect of protonation. For R = Ph (3a), 4-F-C6H4 (3b), 4-I-C6H4 (3c) 4-MeO-C6H4 (3d-H), 2-pyridyl (3e) and 2-pyridyl-H (3e-H), crystal structures were elucidated, and selected structural features are discussed below. Scheme 2. Synthesis of {B12}-based amides 3 and interconversion between their dianionic and monoanionic forms; compounds 3a-d were prepared according to [37].
Single crystals of 3a, 3b, 3c, 3d-h, 3e and 3e-H were obtained from acetonitrile, acetone, acetonitrile-acetone or acetonitrile-methanol solutions. ORTEP representations are displayed in Figure 3, and a summary of structural parameters is given in Table 1, including data for O-protonated 3a-H, originally reported by Gabel and coworkers [34]. The seven compounds can be grouped into the series 3a/3b/3c/3e/3e-H and 3a-H/3d-H. For the former series, distances (Å) fall within B1-N1 1.51-1.52, N1-C1 1.31-1.33 and C1-O1 1.23-1. 25. These compounds thus exhibit strong structural resemblence to classical organic amides. For the latter pair, observed ranges (Å) are B1-N1 1.53-1.58, N1-C1 1.26-1.30 and C1-O1 1.31-1. 34. These values are consistent with O-protonation, leading to a more pronounced allyl cation-type equalization of bond lengths. On the other hand, all seven products share two features: The central carbon atom C1 has perfect trigonal-planar geometry with a sum of angles of 360 • . Furthermore, the torsion angles O1-C1-C2-C3 (O1-C1-C2-N2 for 3e-H) fall in the range of -18 • to +32 • and indicate a certain degree of conjugation between the aromatic rings and the N1-C1-O1 π system.  34. These values are consistent with O-protonation, leading to a more pronounced allyl cation-type equalization of bond lengths. On the other hand, all seven products share two features: The central carbon atom C1 has perfect trigonal-planar geometry with a sum of angles of 360°. Furthermore, the torsion angles O1-C1-C2-C3 (O1-C1-C2-N2 for 3e-H) fall in the range of -18° to +32° and indicate a certain degree of conjugation between the aromatic rings and the N1-C1-O1 π system.  1 Parameters of one of the two molecules in the asymmetric unit; 2 data from reference [34]; 3 torsion angle O1-C1-C2-N2 for 3e-H.

Synthesis of {B12}-based Ureas
{B12}-based ureas with N{B12},N'(aryl) substitution have not been reported before. The synthetic strategy to prepare dodecaboranyl N,N-dialkyl ureas recently reported by our group involved the combination of 2 with dialkylcarbamoyl chlorides [39]. We wondered whether aromatic isocyanates could be used instead of carbamoyl chlorides to achieve the new substitution pattern, given the  1 Parameters of one of the two molecules in the asymmetric unit; 2 data from reference [34]; 3 torsion angle O1-C1-C2-N2 for 3e-H.

Synthesis of {B 12 }-based Ureas
{B 12 }-based ureas with N{B 12 },N (aryl) substitution have not been reported before. The synthetic strategy to prepare dodecaboranyl N,N-dialkyl ureas recently reported by our group involved the combination of 2 with dialkylcarbamoyl chlorides [39]. We wondered whether aromatic isocyanates could be used instead of carbamoyl chlorides to achieve the new substitution pattern, given the commercial availability of many ArNCO reagents. We found that the reaction of 2 with aromatic isocyanates under basic conditions directly leads to the formation of the corresponding urea derivatives of the structure {B 12

Synthesis of Dodecaboranyl Isocyanate
Isocyanates are important intermediates in organic synthesis that are used in the manufacture of, e.g., agrochemicals and polyurethanes [41]. Only one publication by Alam and coworkers from 1989 mentioned the isolation of dodecaboranyl isocyanate 8 [40]. It was prepared via the reaction of [B12H11(CO)] − with NaN3 and analyzed by 11 B-NMR and IR spectroscopy. However, further characterization was not given, and in particular the crystal structure was not reported. Because the isocyanate moiety serves as versatile functional group handle capable of providing access to a number of novel {B12}-based derivatives, we were interested in resynthesizing 8. However, multiple attempts to reproduce the original procedure were not successful in our laboratory, and we therefore sought to establish an alternative route. Since dodecaboranyl N,N-dialkyl ureas can be prepared easily [39], their thermal fragmentation appeared as an attractive strategy. Indeed, treatment of 2 with base and ClC(O)NMe2 to give the intermediate urea, followed by heating in water, afforded 8 in 25% overall yield (Scheme 4). The yield of this sequence is rather low, and efforts to improve the protocol are ongoing.

Synthesis of Dodecaboranyl Isocyanate
Isocyanates are important intermediates in organic synthesis that are used in the manufacture of, e.g., agrochemicals and polyurethanes [41]. Only one publication by Alam and coworkers from 1989 mentioned the isolation of dodecaboranyl isocyanate 8 [40]. It was prepared via the reaction of [B 12 H 11 (CO)] − with NaN 3 and analyzed by 11 B-NMR and IR spectroscopy. However, further characterization was not given, and in particular the crystal structure was not reported. Because the isocyanate moiety serves as versatile functional group handle capable of providing access to a number of novel {B 12 }-based derivatives, we were interested in resynthesizing 8. However, multiple attempts to reproduce the original procedure were not successful in our laboratory, and we therefore sought to establish an alternative route. Since dodecaboranyl N,N-dialkyl ureas can be prepared easily [39], their thermal fragmentation appeared as an attractive strategy. Indeed, treatment of 2 with base and ClC(O)NMe 2 to give the intermediate urea, followed by heating in water, afforded 8 in 25% overall yield (Scheme 4). The yield of this sequence is rather low, and efforts to improve the protocol are ongoing.

Synthesis of Dodecaboranyl Isocyanate
Isocyanates are important intermediates in organic synthesis that are used in the manufacture of, e.g., agrochemicals and polyurethanes [41]. Only one publication by Alam and coworkers from 1989 mentioned the isolation of dodecaboranyl isocyanate 8 [40]. It was prepared via the reaction of [B12H11(CO)] − with NaN3 and analyzed by 11 B-NMR and IR spectroscopy. However, further characterization was not given, and in particular the crystal structure was not reported. Because the isocyanate moiety serves as versatile functional group handle capable of providing access to a number of novel {B12}-based derivatives, we were interested in resynthesizing 8. However, multiple attempts to reproduce the original procedure were not successful in our laboratory, and we therefore sought to establish an alternative route. Since dodecaboranyl N,N-dialkyl ureas can be prepared easily [39], their thermal fragmentation appeared as an attractive strategy. Indeed, treatment of 2 with base and ClC(O)NMe2 to give the intermediate urea, followed by heating in water, afforded 8 in 25% overall yield (Scheme 4). The yield of this sequence is rather low, and efforts to improve the protocol are ongoing.

General
If not otherwise specified, reagents and organic solvents were commercially available and used without further purification. Anhydrous solvents were prepared by passage through activated Al2O3 and stored over 3 Å molecular sieves. CD3CN and CD2Cl2 were purchased from Cambridge Isotope Laboratories and filtered through Al2O3 prior to use. [B12H12] 2− and [B12H11NH3] − salts and dodecaborate amides 3a-e were prepared according to the literature [10,36].
Glassware for air-sensitive reations was dried at 150 °C and allowed to cool in a vacuum. Reactions carried out in a glovebox were run under a nitrogen atmosphere with O2, H2O < 1 ppm.
Thin-layer chromatography (TLC) was carried out using silica gel 60, F254 with a thickness of 0.25 mm. Column chromatography was performed on silica gel 60 (200-300 mesh).
Low-resolution ESI-MS data were recorded on Advion Expression CMS instrument (Advion, Ithaca, NY, USA). High-resolution MS data were recorded using IT-TOF detection (Shimadzu, Kyoto, Japan) equipped with an electrospray ionization source (ESI). Accurate mass determination was corrected by calibration using sodium trifluoroacetate clusters as a reference.
Single-crystal X-ray diffraction studies were performed on an Oxford Diffraction Gemini A Ultra diffractometer (Agilent Technologies, Santa Clara, CA, USA) equipped with an 135 mm Atlas CCD detector and using Mo K-a radiation.

General
If not otherwise specified, reagents and organic solvents were commercially available and used without further purification. Anhydrous solvents were prepared by passage through activated Al 2 O 3 and stored over 3 Å molecular sieves. CD 3 CN and CD 2 Cl 2 were purchased from Cambridge Isotope Laboratories and filtered through Al 2 O 3 prior to use. [B 12 H 12 ] 2− and [B 12 H 11 NH 3 ] − salts and dodecaborate amides 3a-e were prepared according to the literature [10,36].
Glassware for air-sensitive reations was dried at 150 • C and allowed to cool in a vacuum. Reactions carried out in a glovebox were run under a nitrogen atmosphere with O 2 , H 2 O < 1 ppm.
Thin-layer chromatography (TLC) was carried out using silica gel 60, F254 with a thickness of 0.25 mm. Column chromatography was performed on silica gel 60 (200-300 mesh).
Low-resolution ESI-MS data were recorded on Advion Expression CMS instrument (Advion, Ithaca, NY, USA). High-resolution MS data were recorded using IT-TOF detection (Shimadzu, Kyoto, Japan) equipped with an electrospray ionization source (ESI). Accurate mass determination was corrected by calibration using sodium trifluoroacetate clusters as a reference.
Single-crystal X-ray diffraction studies were performed on an Oxford Diffraction Gemini A Ultra diffractometer (Agilent Technologies, Santa Clara, CA, USA) equipped with an 135 mm Atlas CCD detector and using Mo K-a radiation.
NMR spectra were recorded on a Bruker AVANCE III 500 spectrometer ( 1 H NMR 500.13 MHz, 13 5.758 mmol, 7 equiv) and a stir bar. THF (4 mL) and DMF (4 mL) were added, and the mixture was stirred at room temperature for 10 min until there was no H 2 evolution anymore. Then pyridine-2-carbonyl chloride hydrochloride PyCOCl·HCl (220.2 mg, 1.237 mmol, 1.5 equiv) was slowly added. The conversion was complete after stirring for 5 h. The flask was transferred out of the glovebox. H 2 O (4 mL) was added, and the pH value of the reaction mixture was adjusted to 2-3 with 1 M aqueous HCl. [NEt 3 H]Cl (300 mg, 2.180 mmol, 2.7 equiv) was added, and the reaction mixture was extracted with MeCN/EtOAc (1:2 v/v). The organic layers were concentrated on a rotary evaporator. The residue was purified by recrystallization from methanol to afford yellowish crystals of [Et 3 1H, B-H). This spectrum contained small signals at 7.18, 6.71 and 6.67 ppm ascribed to residual aniline. 13