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5th November 2016 @ 23:25

The aim of this experiment is to produce 2-piperidinylbenzaldehyde using Buchwald-Hartwig Pd (II) catalysed cross coupling1. The starting materials being used are 2-bromobenzaldehyde and Piperidine:

 

Figure 1: Preparation of 2-piperidinylbenzaldehyde via Buchwald-Hartwig amination.

Table 1: Table of Reagents used in experiment.

Reagent

Molecular Weight (g/mol)

Density

(g/mL)

Moles

(mmol)

Quantities

2-bromobenzaldehyde

 

185.02

1.585

1.08

0.130 mL

Palladium (II) acetate

 

224.50

-

0.008

0.002 g

Rac-BINAP

 

622.67

-

0.009

0.0061 g

Piperidine

 

85.15

0.862

3.28

0.324 mL

Caesium carbonate

 

325.82

-

0.859

0.2864 g

Toluene

 

92.14

-

-

5 mL

Procedure

2-bromobenzaldehyde (0.13 mL, 1.08 mmol) was taken into toluene (5 mL) and the flask placed under a nitrogen atmosphere. Piperidine (0.32 mL, 3.28 mmol), rac-BINAP (0.006 g, 0.009 mmol), Caesium carbonate (0.29 g, 0.86 mmol) and Palladium (II) acetate (0.002 g, 0.008 mmol) were added sequentially whilst maintaining the nitrogen atmosphere. The solution was then degassed for 10 minutes, after which time the reaction was heated at reflux for 12 hours.

The resulting mixture was an opaque yellow solution.

Figure 2: Apparatus showing reflux under nitrogen atmosphere.

TLC analysis was undertaken (EtOAc/Pet. Ether 1:1) but no new product was observed. The mixture was poured into half-saturated K2CO3 solution and extracted into Dichloromethane (3 x 20 mL). the organic phases were combined and washed with Brine (10 mL). The organic phase was then dried (MgSO4), filtered and the solvent removed in vacuo to give the crude material as a yellow, oily solution (0.2866 g).

1H NMR of the crude product was taken, which showed inconclusive results, therefore the reaction was terminated.

 Figure 3: NMR of crude product.

A nucleophilic aromatic substitution (SNAr mechanism) was suggested as an alternative route that may lead to a purer sample.

References

C. Rabong, C. Hametner and K. Mereiter, et al., Heterocycles, 2008, 75, 813.