Base-Catalyzed Direct Transformation of Benzylamines into Benzyl Alcohols

Abstract

Benzylamines were directly transformed into benzyl alcohols in superheated aqueous methanol in the presence of a base catalyst. This process is simple and will provide an alternative industrial route to benzyl alcohols such as xylene glycols.

Key words

alcohols - amines - catalysis - substitution - solid-phase synthesis

References and Notes

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• 11a

  After our patent application,^¹¹b another patent application^¹¹c was published. It was reported that when benzylamine and an equivalent amount of glycolic acid were heated in supercritical methanol, the amide was probably generated in situ, and then it was converted into benzyl alcohol with good yield.

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• 11c Kamimura A, Kaiso K, and Sugimoto T. inventors; PCT Int. Appl. WO  016409. 

12

We examined the reaction of MXG and methylamine as a representative of the reverse reaction, that is, transformation of benzyl alcohols into benzylamines. So far, MXDA was not obtained.

13

In order to check metal leaching from the stainless-steel autoclave, ICP analysis of the reaction solution was performed [reaction conditions: MXDA/MeOH/H₂O/NaOH = 1:110:70:1.4 (molar ratio), 240 ˚C, 2 h]. The concentrations of Fe, Cr, Ni, and Mo were 0.018, 0.058, 0.0, and 3.0 ppm, respectively. The reaction also conducted in a glass vessel when it was carried out in 1-undecanol under reflux at atmospheric pressure. Therefore, it was considered that metal leaching from the reaction vessel was minute and its effect was marginal.

14

MXDA, mono-alcohol, MXG, MeOH, and methylamine were only observed, and no other byproducts or inter-mediates were detected in the time-course GC analysis of the reaction.

15

Reactions under N₂ and H₂ (initial pressure: 1 MPa) were investigated and compared with those at 1 atm N₂. Even under H₂ pressure, the reaction smoothly proceeded and no differences were observed. Combined with the fact that no byproducts or intermediates were detected, it was thus not considered probable that the reaction proceeded via imine or aldehyde intermediates.

16

From the fact that the yields of N-methyl and N,N-dimethyl benzylamine were very low, it was apparent that N-methylation by methanol did not occur during the reaction

17

Preparation of m -xylene glycol (MXG); Typical Procedure (Table 1)
To a 30-mL autoclave was added MXDA (0.30 g, 2.2 mmol), catalyst (0.1 g), and MeOH (7.4 g), and then the inner gas was replaced by N₂. The mixture was heated at 240 ˚C for 2 h, and then cooled in an ice-water bath. The yield was determined by GC analysis using tridecane as internal standard. The crude products were purified by Kugelrohr distillation.
Spectral data of MXG (Table  [³] , entry7): ^¹H NMR (500 MHz, CD₃OD): δ = 4.60 (s, 4 H), 7.24-7.34 (m, 4 H). ^¹³C NMR (126 MHz, CD₃OD): δ = 65.2, 126.6, 126.9, 129.4, 142.8.

18

Preparation of benzyl alcohol derivatives (Table 4): To a 30-mL autoclave was added benzylamine derivative (4.4 mmol for entry 9, 11, and 12, and 2.2 mmol for the others), powdered NaOH (0.1 g, 2.5 mmol), MeOH (7.4 g), and H₂O (2.9 g), then the inner gas was replaced by N₂. The mixture was heated at 240 ˚C for 2 h, and then cooled in an ice-water bath. The reaction mixture was neutralized with 1 M HCl (2.5 mL, 2.5 mmol). GC yield was determined by GC analysis using tetradecane (entry 4) and tridecane (for the others) as internal standard. For entry 1, the solutions were dried over Na₂SO₄, concentrated, and purified by silica-gel column chromatography (hexane-EtOAc, 75:25 v/v). The other products were purified by Kugelrohr distillation.
Spectral data of benzyl alcohol (Table  [4] , entry1): ^¹H NMR (500 MHz, CD₃OD): δ = 4.59 (s, 2 H), 7.23-7.33 (m, 5 H). ^¹³C NMR (126 MHz, CD₃OD): δ = 65.2, 126.6, 126.9, 129.4, 142.8. All other products were characterized by comparison of GC retention time with chemical reagents purchased from commercial suppliers.