Nucleophilic displacement of ammonia from ammonia borane for the preparation of alkylamine-, pyridine- and phosphine-boranes

P. Veeraraghavan Ramachandran* and Ameya S. Kulkarni
Herbert C. Brown Center for Borane Research, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA. E-mail: chandran@purdue.edu

Received 14th April 2014 , Accepted 29th May 2014

First published on 29th May 2014


Abstract

A near quantitative and safe preparation of a series of aliphatic amine- and phosphine-boranes from ammonia borane (AB) in refluxing THF has been achieved by exploiting the volatility of ammonia. A one-pot preparation of lithium aminoborohydrides from AB has also been described.


Amine- and phosphine-boranes,1,2 the classic Lewis base–Lewis acid (LB–LA) pairs have been known for over a century.3 During the initial days, their methods of preparation and properties were the primary focus of chemists.4 Amine-boranes can be readily prepared via ligand exchange using borane–tetrahydrofuran (borane–THF) or borane-methyl sulfide (BMS).1a,5 The low molarity of the former, the stench of the latter and the pyrophoric nature of both are some of the major drawbacks associated with these procedures. In addition, removal of dimethyl sulfide for re-use of the solvent (THF) adds additional steps in the synthetic process with BMS.

Amine-boranes have also been made via trans-amination.6 The equilibrium in this protocol depends on the nucleophilicity of the incoming amine and can be shifted towards a particular amine-borane by distillation of the volatile amine. One of the problems with this protocol is that the lower boiling amine is only partly removed, thus preventing the completion of the reaction. In certain cases, attempted distillation of the liquid residue has been reported to explode violently.6 Synthesis of amine- and phosphine-boranes from metal hydrides7 and borohydrides8 has also been reported.

Exchange reaction of amine-boranes with phosphines is also known (Scheme 1). Hawthorne and coworkers examined the kinetics of the displacement reaction of trialkylamine-boranes with phosphines and proposed an SN2 mechanism at the tetrahedral boron center (SN2B).9 The SN2B reaction kinetics for the amine exchange of ammonia borane (AB, 1) with N,N,N-triethylamine (Et3N, 2a) in a flame-sealed NMR tube at 35 °C, without a preparative procedure, has been recently described.10


image file: c4ra03397c-s1.tif
Scheme 1 Synthesis of phosphine-boranes by ligand exchange.

Depending on the strength of the complexes, a variety of applications have been found for amine-boranes.1 They have been utilized for reduction of carbonyls,11 reductive amination,12 hydrogenation of olefins,13 metal-free hydroboration of alkenes,14 curing agents in epoxy resin preparation,15 preparation of lithium aminoborohydrides,16 or as pharmacologically active moieties,17 etc. Most recently, amine-boranes have gained significance as hydrogen storage materials.18 In comparison, phosphine-boranes have been traditionally used as intermediates to prevent the oxidation of phosphine ligands; though several direct applications have been reported recently.2

As part of our ongoing projects on hydrogen storage materials for portable fuel cell applications,19 we needed large quantities of amine-boranes. A very practical and general synthetic protocol was envisaged for amine- and phosphine-boranes via the trans-amination (Scheme 2) and phosphination of AB, which can be readily synthesized from sodium borohydride.19 This protocol would avoid the aforementioned difficulties with borane–THF and BMS due to the high stability and non-toxic nature of AB. An added advantage is that the equilibrium could be shifted to the desired product in quantitative yields since the outgoing ligand is a gas. Our successful preparation of amine- and phosphine-boranes from AB is described herein.


image file: c4ra03397c-s2.tif
Scheme 2 Trans-amination of ammonia borane.

To begin with, we examined the conditions necessary for the trans-amination of AB with a trialkylamine, such as Et3N in diethyl ether (Et2O). A tertiary amine was chosen since this represented the upper limits of the protocol. The reaction progress was monitored by 11B NMR spectroscopy. The reaction was 23% complete at room temperature (RT) in 20 h. In refluxing Et2O, the reaction was 70% complete within the same period. Changing the solvent to THF, only 5% amine exchange was observed in 20 h, at RT. We were apprehensive about raising the reaction temperature due to the potential for dehydrogenation of AB.20 Fortuitously, in the presence of the added amine, no decomposition of AB was observed under refluxing conditions in THF at 1 M concentration and the reaction was complete in 6 h.21 Removal of solvents provided 97% yield of Et3N–BH3 (3a). The purity of the product amine-borane was determined by 11B NMR spectroscopy, hydride analysis5 and by comparing with physical data available in the literature.22

The molar equivalents of the incoming nucleophilic amine were varied to verify the SN2B pathway. The reaction proceeded at almost 2× the rate when two equivalents of the incoming amine were used and the rate was about 4× when the amine equivalents were doubled again. These results corroborate the SN2B mechanism similar to the classic SN2 reactions at carbon centers.23

The effect of reaction concentration was then examined to achieve optimal conditions. The reported maximum solubility of AB in THF is 7.2 M at 20 °C.24 Accordingly, the trans-amination was conducted at 1, 2 and 4 M concentrations (Table 1). Though the rate accelerates with increase in concentration, we settled for a 2 M solution for the reaction with Et3N, since further concentration led to the formation of ∼3% AB dehydrogenation products. We carried out trans-amination with yet another trialkylamine (N-methylpyrrolidine, 2b) in refluxing THF in 2 M concentration and obtained 97% yield of the corresponding amine-borane (3b) within 3 h.

Table 1 Effect of concentration on the rate of trans-amination of AB with Et3N
Entry Conc. (M) % reactiona
60 (min) 120 (min) 195 (min) 255 (min) 315 (min) 390 (min)
a Determined by 11B NMR spectroscopy.b ∼3% AB dehydrogenation products were observed in 11B NMR spectrum.
1 1 61% 84% 92% 98% 99% 100%
2 2 68% 88% 96% 99% 100%
3b 4 86% 97% 100%


While N,N-diethylamine (2d), could be cleanly converted to the corresponding amine-borane 3d within 0.25 h in refluxing THF at 4 M concentration, other 2°-amines, such as piperidine (2e), pyrrolidine (2f) and morpholine (2g) required 1 h for the trans-amination with quantitative yields of the products. A bulky 2°-amine, N,N-diisopropylamine (2h) proved to be an exception necessitating the dilution of the reaction mixture to 1 M and the reaction was complete within 1 h, yielding 91% of the product (3h).25 This could be rationalized using steric strain of the LB–LA complexes.26

While a 4 M THF solution of AB at reflux forced trans-amination of 1-propanamine (2j) within 1 h providing the corresponding amine-borane 3j in 95% isolated yield, cyclohexylamine (2k) yielded the corresponding amine-borane 3k within 0.25 h under similar conditions. As can be seen from the summary (Table 2), the rate of the reaction appears to be dependent on the nucleophilicity of the incoming amine. N,N-Diisopropylethylamine (2c) and 2,2,6,6-tetramethylpiperidine (2i) failed to force clean trans-amination, further proving that the reaction follows an SN2B mechanism.

Table 2 Synthesis of amine-boranes from ammonia borane
Entry Amine Reaction conditions Amine-boranes
Class No. Amine Time (h) Conc. (M) No. Yielda (%) 11B NMR (ppm)
a Isolated yield.b Decomposition of AB.c Higher concentration of the reaction mixture led to AB dehydrogenation products.d NR = not clean reaction.
1 None 10 1 b
2 3°- 2a N,N,N-Triethylamine 6 2c 3a 97 −12.9
3 2b N-Methylpyrrolidine 3 2c 3b 97 −10.0
4 2c N,N-Diisopropylethylamine NRd 1 3c
5 2°- 2d N,N-Diethylamine 0.25 4 3d 98 −16.6
6 2e Piperidine 1 4 3e 96 −14.9
7 2f Pyrrolidine 1 4 3f 96 −16.5
8 2g Morpholine 1 4 3g 97 −14.8
9 2h N,N-Diisopropylamine 1 1c 3h 91 −21.1
10 2i 2,2,6,6-Tetramethylpiperidine NRd 1 3i
11 1°- 2j 1-Propanamine 1 4 3j 95 −19.6
12 2k Cyclohexylamine 0.25 4 3k 96 −20.9
13 3°- 2l Pyridine 6 1c 3l 94 −11.6


Aromatic primary amine-boranes are known to undergo spontaneous dehydrogenation at ambient conditions.27 Attempted trans-amination of AB with a representative aromatic 1°- and 2°-amine, such as aniline and N-ethylaniline respectively, led to the dehydrogenation of the product as stated above. Surprisingly, attempted trans-amination of N,N-diethylaniline also failed, resulting in the formation of AB dehydrogenation products, pointing to the weakness of the incoming nucleophile during the SN2B reaction.

Gratifyingly, pyridine (2l) displaced ammonia completely within 6 h in 1 M refluxing THF to produce pyridine-borane (3l) in 95% isolated yield. It is noteworthy that although pyridine-borane is known to be thermally unstable,6 no difficulties were encountered during the near quantitative conversion of AB to pyridine-borane.

This protocol was then examined for the preparation of phosphine-boranes. As expected, representative trisubstituted phosphines, triphenylphosphine (4a) and tricyclohexylphosphine (4b) were converted to the corresponding phosphine-boranes 5a and 5b, in 8 h and 12 h, respectively at 1 M concentration. A 2°-phosphine, diphenylphosphine (4c) achieved ammonia displacement yielding the adduct 5c within 10 h. However, the borane adduct (5d) from a 1°-phosphine, phenylphosphine (4d), underwent decomposition under the reaction conditions and could not be isolated. The results are summarized in Table 3. A more detailed study on the scope of phosphine-borane synthesis from AB is currently under way in our laboratories.

Table 3 Synthesis of phosphine-boranes from ammonia boranea

image file: c4ra03397c-u1.tif

Entry Phosphine Time (h) Phosphine-borane
No. Phosphine No. Yieldb (%) 11B NMR (ppm)
a All reactions were carried out at 1 M concentration of AB in THF.b Isolated yield.c Decomposition of the product under reaction conditions.
1 4a Triphenylphosphine 8 5a 96 −38.1
2 4b Tricyclohexylphosphine 12 5b 95 −43.6
3 4c Diphenylphosphine 10 5c 70 −40.0
4 4d Phenylphosphine 32 5d c −42.0


Having achieved a simple preparation of amine-boranes in high (91–98%) yields and purity, without the need for any purification, the practicality of our protocol was demonstrated with a 1 mole-scale synthesis of 3a. To further demonstrate the utility of this procedure, a one-pot preparation of lithium aminoborohydrides (LAB reagents) was designed. Singaram and coworkers have extensively studied LAB reagents and described myriad applications.28 Thus, AB (0.1 mol) was treated with 0.1 mol of morpholine (2g) in refluxing THF for 1 h, followed by the in situ addition of n-butyllithium at 0 °C. Upon warming to RT, a quantitative formation of the corresponding LAB reagent 6 (Scheme 3) was achieved, as was determined by 11B NMR spectroscopy. This aminoborohydride (6) provided identical results for the reduction of a ketone (acetophenone) and tertiary amide (N,N-dimethylbenzamide), as reported in the literature.16


image file: c4ra03397c-s3.tif
Scheme 3 One-pot synthesis of lithium aminoborohydride.

Conclusions

We have achieved a simple preparation of aliphatic 1°-, 2°- and 3°-amine-boranes, pyridine-borane and phosphine-boranes via amine/phosphine-exchange reactions using ammonia borane. The gaseous nature of ammonia aids in the completion of the reaction and the products are readily isolated by removal of the solvent, which is recycled. Scale-up of the reaction has been demonstrated and this protocol has also been extended for a one-pot synthesis of lithium aminoborohydrides. This protocol avoids several of the problems associated with the current procedures for the preparation of amine-boranes. The ready synthesis of ammonia borane from sodium borohydride makes this a very economical route to these compounds. We believe that this protocol will be welcomed by organic and materials chemists.

Acknowledgements

The authors thank the Herbert C. Brown Center for Borane Research for financial assistance of this project.

Notes and references

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Footnote

Electronic supplementary information (ESI) available: Representative procedures for the synthesis of amine- and phosphine-boranes as well as a one-pot procedure for the synthesis of LAB reagent. The physical data and 11B NMR spectra of all of the compounds are also included. See DOI: 10.1039/c4ra03397c

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