Synthesis
The general procedure for the synthesis of 4-cyanophenylacetonitrile from the compound (CAS: 773837-37-9) and 4-cyanobenzyl bromide is as follows:
1. Synthesis of doubly radiolabeled C3-conjugate [14C/3H]-1:
a) The reaction was carried out using Na14CN (0.33 eq.) and TBAB (0.17 eq.) in a solvent mixture of CH2Cl2/H2O (1:1, v/v) at room temperature overnight.
b) Subsequently, 2M NaOH (2.8 eq.) was added, followed by the addition of concentrated HCl for neutralization.
2. Synthesis of 4-(Cyanomethyl)benzonitrile (10):
a) Tetrabutylammonium bromide (14 mg, 0.043 mmol, 0.5 eq.) and sodium cyanide (4.2 mg, 0.085 mmol, 1 eq.) were added to a 4 mL vial.
b) Dichloromethane (1.5 mL) and water (1.5 mL) were added followed by 4-(bromomethyl)benzonitrile (0.050 g, 0.26 mmol, 3 eq.).
c) The reaction system was stirred vigorously at room temperature overnight.
d) After completion of the reaction, the aqueous phase was separated from the organic layer, which was extracted twice with CH2Cl2.
e) The organic layers were combined and the solvent was blown dry.
f) The crude product was purified by passing through a silica gel column (Pasteur pipette), eluting with 70% EtOAc/hexane to give 4-(cyanomethyl)benzylnitrile (9.2 mg, 76%) as a colorless oil, which solidified to a white solid.
Product characterization data were in agreement with the literature (Velcicky, J.; Soicke, A.; Steiner, R.; Schmalz, H.-G. J. Am. Chem. Soc. 2011, 133, 6948-6951).
1H NMR (CDCl3, 500 MHz) δ 7.70 (d, 2H, J = 8.5 Hz), 7.48 (d, 2H, J = 8.5 Hz), 3.84 (s, 2H); 13C NMR (CDCl3, 151 MHz) δ 135.3, 133.0, 128.9, 118.2, 116.6, 112.5, 23.9 ; HPLC purity: 91%, tR = 1.9 min (Method 1).
