The Synthesis Of A Multistep Synthesis Procedure

A multistep synthesis procedure was used to synthesize benzocaine from p-toluidine (Scheme 1). In step one, p-toluidine was acetylated to produce p-acetotoluidide to protect the amine from oxidation. In step two, the methyl substituent on p-acetotoluidide was oxidized to produce p-acetamidobenzoic acid. In step three, p-acetamidobenzoic acid was hydrolyzed to remove the protecting group to produce p-aminobenzoic acid. In step four, p-aminobenzoic acid was esterified to produce benzocaine. A melting point range (Table 1) and 1H NMR spectrographs (Figures 1-4) were acquired for each product to confirm product identity at each step.

The experimental melting range for each compound was within one to two degrees of the literature melting point which indicated possible contaminates. This was due to incomplete drying and/or errors during synthesis.
1H NMR spectra were acquired for each compound at 300 MHz and were provided by Dr. Kim White. The 1H NMR spectrum for each compound was analyzed below (Figures 1-4).
The 1H NMR for p-acetotoluidide (Figure 1) contained five significant signals. Four of the signals were produced by p-acetotoluidide while the fifth signal (7.25 δ) was produced by the 1H NMR solvent, CDCl3. Due to proton exchange due to hydrogen bonding, there was no significant signal produced for the hydrogen bonded to the amide group. Due to this quality of hydrogen bonding the signal can manifest as broad, at the wrong chemical shift, or be absent. In this case, the signal produced by the hydrogen bonded to the amide group was absent. A list of the types of hydrogens and their chemical shifts for p-acetotoluidide was recorded (Table 2).

The 1H NMR for p-acetamidobenzoic acid (Figure 2) contained five significant signa...

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...d, water (10 mL) was added and the resulting solution was neutralized to pH 7-8 by adding sodium carbonate (1.51 g, 14.2 mmol). The mixture was extracted twice with dichloromethane (two 10 mL portions). The combined organic layers were washed with water (10 mL) and sodium chloride (10 mL). The remaining organic layer was dried with anhydrous sodium sulfate. The solution was filtered and the remaining solvent was evaporated on a hot plate. Crystallization of benzocaine occurred. The crystals were recrystallized with methanol and water while heating. The reaction was cooled in an ice bath. The pale yellow precipitate was removed via vacuum filtration and dried under continuous filtration (0.17 g, 1.03 mmol). MP = 85-87 ͦC (literature value 88-90 ͦC); 1H NMR (300 MHz, CDCl3): δ 7.83-7.86 (d, 2H), 6.61-6.64 (d, 2H), 4.27-4.34 (q, 2H), 4.10 (s, 2H), 1.32-1.37 (t, 3H).