Meeting 8 (Lidocaine synthesis Part 1+2)

Meeting 8 (Condensed Key)

1. a. The reaction of iron(II) ions with borohydride can be described by

Note that the iron product in the reaction highly depends on the solvent being used in the reaction.

b. The main advantage is in the use of non-toxic iron versus the use of toxic stannous chloride. In addition, less concentrated acids are used in the reaction. A disadvantage is that the reaction takes much longer (about one hour vs. 10 min) and also requires some heat.

c. The 'optimal temperature' temperature for the reaction is about 40 ^oC. At lower temperatures, the reaction appears too slow (requiring 2-4 hours) while at higher temperatures, the reaction of water with the iron appears to play a more important role as well, reducing the amount of available reducing agent.

d. The sodium chloride addition increases the polarity of the organic layer and therefore decreases the solubility of the organic compounds (amine, nitro compound, etc.). This will make it easier to extract them from the aqueous layer.

e. The extraction with hydrochloric acid leads to the transfer of the amine into the aqueous layer because it is protonated (RNH₃⁺Cl^-). The nitro compound and the bulk of the phase transfer catalyst (Adogen) remain in the organic layer here.

f. The product is a base (primary amine), which would absorb much stronger on acidic drying agents like anhydrous sodium sulfate or anhydrous magnesium sulfate. Potassium carbonate is used as drying agent because the compound displays a lower affinity towards a basic drying agent.

2. a. The procedure in the reader asks to use 1.1 equivalents of the acyl chloride. The given amount of 2,6-dimethylaniline is equal to 9.90 mmol (=(1.20 g)/(121.18 g/mol). Thus, 10.9 mmol of the acetyl chloride should be used, which is equal to 0.87 mL (=(10.9 mmol*112.94 g/mol)/1.42 g/mL).

b. Acyl chlorides are very reactive and among other compounds also react with water (i.e., moisture) to form the corresponding carboxylic acid.

c. Glacial acetic acid is used as solvent because it does not introduce water into the system. In addition, the unreacted ammonium salt is soluble in glacial acetic acid.

d. The infrared spectrum of the amide displays only one N-H peak at ν=3214 cm^-1 and a strong carbonyl peak at ν=1648 cm^-1. The peaks that are due to the primary group (ν=1622 cm^-1 (NH₂, bend), 3473 cm^-1 (asym. stretching), 3388 cm^-1(sym. stretching)).