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The Royal Society of Chemistry"

Buchwald-Hartwig amination of a bromopyridine with cyclohexane-1,2-diamine

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Submitted: July 8, 2013, published: July 10, 2013

Authors

A contribution from 

Reaction Scheme

Chemicals

(+/-)-trans‑1,2‑diaminocyclohexane (Aldrich)
2-bromo-6-methyl pyridine (Aldrich)
(±)-BINAP
[Pd2(dba)3] (Aldrich)
NaOBut (Aldrich)
Toluene (distilled over sodium)

Procedure

Toluene (50 mL) was added to a large Schlenk vessel charged with (+/-)-trans‑1,2‑diaminocyclohexane (1.0 g, 8.8 mmol), 2-bromo-6-methyl pyridine (3.0 g, 18 mmol), (±)-BINAP (218 mg, 0.35 mmol), [Pd2(dba)3] (160 mg, 0.18 mmol) and NaOBut (2.4 g, 25 mmol).  The resulting deep red/brown mixture was heated for 4 h at 80°C with stirring.  On cooling to room temperature diethyl ether (50 mL) was added.  The resultant yellow mixture was washed with brine (2 x 30 mL), dried over MgSO4 and the solvent removed by evaporation under reduced pressure.  The yellow product was recrystallised from pentane / diethyl ether (yield 1.72 g, 60 %).

Author Comments

Reaction was carried out under an inert atmosphere of argon by using a dual manifold vacuum/argon line and standard Schlenk techniques, or in an MBraun dry box. Note that this is the racemate, but no epimerisation was noted in the product i.e. no cis product detected by NMR.

Data

1H NMR (293 K, d6-benzene) d 1.25 (m, 4H, cyclohexane-CH2), 1.58 (m, 2H, cyclohexane-CH2), 2.30 (m, 2H, cyclohexane-CH2), 2.52 (s, 6H, Py-CH3), 4.05 (m, 2H, ipso cyclohexane‑CH), 5.39 (s, 2H, NH), 5.97 (d, 3JHH = 7 Hz, 2H, Py-CH), 6.34 (d, 3JHH = 7 Hz, 2H, Py-CH), 7.06 (t, 3JHH = 7 Hz, 2H, Py-CH).

13C{1H} NMR (293 K d6-benzene) d 25.1 (Py-CH3), 25.6 (cyclohexane-CH2), 33.6 (cyclohexane-CH2), 56.5 (cyclohexane-CH), 105.9 (Py-CH), 111.6 (Py-CH), 137.6 (Py-CH), 157.0 (PyCqCH3), 159.3 (PyNCqN).

IR (nujol, cm-1): 3292, 2726, 2669, 1605, 1582, 1519, 1336, 1295, 1226, 1153, 1115, 1099, 1029, 986, 948, 933, 778, 728. 

Anal. Calcd. for C18H24N4: C, 72.94; H, 8.16; N, 18.90.  Found: C, 73.06; H, 8.09; N, 18.86.

MS (CI) m/z 297 (M+), 202 (M+-PyCH3), 187 (M+-NH and PyCH3), 109 (M+-2 x PyCH3).

Lead Reference

E. J. Crust, I. J. Munslow and P. Scott, Journal of Organometallic Chemistry, 2005, 690, 3373-3382.http://dx.doi.org/10.1016/j.jorganchem.2005.04.019

Keywords

2-diaminocyclohexane, addition, amination, amines, aromatics/arenes, Buchwald-Hartwig, trans-1 2-bromo-6-methyl pyridine, transition metal catalysed