You will synthesize lidocaine via a series of synthetic reactions according to the instructions below. A single report is required with IR and nmr spectra of the final product. Be sure to calculate % yield for each step of your synthesis as well as the overall % yield.


multistep synthesis of lidocaine


first lab:



Reduction of 1,3-dimethyl-2-nitrobenzene to 2,6-dimethylaniline


Ar-NO2 + SnCl2.2H2O, HCl ---> Ar-NH3+,Cl- + SnCl4


-make up the following two solutions:


solution 1: 0.10 mole (22.6 g) SnCl2.2H2O in 40 mL of conc. HCl (warm to dissolve)


solution 2: 0.033 mole (5 g, 4.5 mL) 1,3-dimethyl-2-nitrobenzene in 50 mL acetic acid


-mix the two solutions and let stand for 15 minutes


-after fifteen minutes, cool in ice bath and vacuum filter


Ar-NH3+,Cl- + KOH ---> Ar-NH2


-tranfer solid to a flask and add 25 mL of water, make strongly basic with 40-50 mL of 8M KOH (caution!)


-cool to room temperature with ice bath


-extract with (1) 25 mL diethyl ether

(2) 10 mL diethyl ether


-wash combined ether extracts with 10 mL water; repeat


-dry over anh. K2CO3


-filter into pre-weighed RB flask and remove diethyl ether by distillation (ether --> waste bottle)


-reweigh flask




Ar-NH2 + Cl-CH2COCl ---> Ar-NHCOCH2-Cl


-residue from above + 25 mL acetic acid


-add (3.7 g, 2.6 mL) α-chloroacetyl chloride (caution!)


-warm to 40-50oC


-add solution: (5 g NaO2CCH3.3H2O in 100 mL water)


-cool, vacuum filter, air dry, weigh, mp



second lab:






-note: all reagents and apparatus must be dry!


-in a 250 mL RB flask, combine the α-chloro-2,6-dimethylacetanilide from above with 45 mL toluene


-calculate the number of moles of α-chloro-2,6-dimethylacetanilide

and add three times that number of moles of diethylamine to the RB.


-attach a water cooled condenser and reflux for 90 minutes.


-cool in an water bath and vacuum filter off the solid that forms. (this is not your product!)


-transfer the filtrate to a separatory funnel and extract with two 25 mL portions of 3M HCl.


-combine the aqueous layers in a 250 mL Erlenmeyer flask and add 50 mL of 8 M KOH to make the solution stronly basic.


-warm the mixture and blow across the surface to remove any excess diethylamine


-cool in an ice bath, continuing to blow and scratch until crystals form.


-vacuum filter the crude lidocain, wash the crystals with cold water and remove from the filter paper immediately.


-let dry on a watch glass, package, weigh, mp, IR & nmr spectra.




Answer the following questions:


1) Write a balanced chemical equation for the reduction of

nitrobenzene with Fe in HCl to form aniline. (Fe --> FeCl3)


2) Draw the structures of at least two by-products produced in the reaction in 1).


3) Why does 2,6-dimethylaniline react with chloroacetyl chloride to produce an amide rather than a secondary amine?


4) Lidocaine is commercially sold in the form of the hydrogen chloride salt. Why?


5) In the reduction of 2,6-dimethylnitrobenzene with stannous chloride, what is the structure of the ppt that is collected by suction filtration?


6) What is the precipitate collected by filtration after the reaction with diethylamine?


7) Why do we use three moles of diethylamine for every mole of the anilide?