Skip to content

Synthesis of Lidocaine Lab

  • by

Hi guys welcome to the lab experiment where we synthesize lidocaine a local anesthetic lidocaine is synthesized in a two-step process in the first step of the reaction to six dimethyl aniline is treated with alpha chloroacetic chloride in acetic acid in the presence of sodium acetate this reaction is a selective substitution at the acyl carbon in a second step of the

Reaction the product of the first step or two six dimethyl phenol plural of c to mine is treated with diethyl amine and that diethyl amine replaces a chlorine in an sn2 type reaction this reaction is our first look at a multi-step synthesis protocol in the laboratory what i want to bring your attention to is at the end of this lab we will be doing a recrystallization

Which is a great form of purification in the lab speaking of the lab let’s head there now in the first step the preparation of two six dimethyl phenol chloroacetic in a clean dry 125 milliliter erlenmeyer flask we put 15 milliliters of glacial acetic acid and to that flask using a pipette we will add three milliliters of two six dimethyl aniline using a syringe

We will add four milliliters of chloroacetic fluoride finally we are going to head 25 milliliters of 50% aqueous sodium acetate to the flask now 60 milliliters of cold distilled water were added to the erlenmeyer as i was getting ready to add the water i realized that the erlenmeyer flask was actually warm to the touch i used a spatula to break up some of the

Solids and get it ready for vacuum filtration i turned on the vacuum system to create suction in my view clear funnel my view clear font is equipped with a filter and now i am pre-wetting it with the cold water which is the solvent so then we need to transfer all of the product under the buettner funnel to filter of the cold water which is the solvent and to start

Drying our product again rinse the erlenmeyer a couple times with cold water to try to get the rest of our salad out of there and we can continue to wash our product then we’re going to use a glass stopper to press down on our product to try to push more of the water out this is another method to dry your product once you’ve left it on the filtration system for a

Few minutes to dry you can begin to start transferring your product into a waynebow so that we can get it ready for the next step of the reaction make sure you remove the filter paper at this point we have synthesized 2 6 dimethyl sun’ll chloro seat amide and we are ready to take it on to the next step let’s make some lidocaine for this reaction we will be doing a

45-minute reflux to provide energy to our reaction or heat we’ll be using the heating mantle connect it to the very ad which is then in turn plugged into the outlet we will be using a reflux setup which involves a water jacketed cool condenser we will transfer our product that we made in the first step the two six dimethyl phenol coracii divided into a 100 milliliter

Round bottom flask the solvent in this reaction is toluene so we will use a graduated cylinder to transfer 25 milliliters of toluene into the round bottom flask finally using a glass pipe path we will add 3.8 of diethyl amine to the reaction vessel you didn’t see me put it in but see the stir bar right there in the reaction once the contents of the round-bottom are

Met you can transfer your on bottom to the heating mantle using the lab jack you can raise the heating mantle and round bottom to meet the bottom of our water cooled condenser don’t forget to secure that joint using your tech plan now the next step is to turn the water on for the water cooled condenser the water is going to go in at the bottom and out at the top to

Keep the bottom of our condenser the coolest to be able to condense our liquid then we’re going to turn the very act on and turn the dial to start the heating process once the contents of the flask begin to boil we can start our timer for 45 minutes for this reflux the reflux apparatus allows for facile heating to a solution but without the lives of solvent that

Would result from an open vessel being heated in the reflux setup solvent vapors are trapped by the condenser and the concentration of the reactants remains constant throughout the process allowing for the constant supply of energy to a reaction over a long period of time using the close up identify where the reflux line exists in this reaction be sure to include

A drawing or description in your notebook once we’ve reflux for 45 minutes we can turn the variac off and take the round bottom flask out of the heating mantle for faster cooling once the contents of the round bottom flask are cooled to room temperature transfer them into a 125 milliliter separatory funnel ensuring that the stopcock is in the closed position and

Now for the extraction part of the lab we will take our toluene layer and wash it four times with five milliliters of distilled water make sure that you shake and vent three times for each extraction once you have two distinct layers you can determine which layer is which by using a pipette with water and seeing if it goes through or if it stays on top in this case

It went through confirming that our aqueous layer is in fact on the bottom now we will remove that bottom layer that aqueous wash for discard and prior to discarding i will verify one last time that that was the aqueous layer and it has in fact abs the toluene fraction will be washed three additional times with five mils of water and those aqueous layers cannot

Be discarded now we will wash that organic layer with 20 milliliters of three molar hydrochloric acid this time we save the aqueous layer and then we will wash that organic layer one more time with twenty milliliters of distilled water once collectively we’ll add this aqueous layer to the original hcl or the combined aqueous layers will be put into a two hundred

Milliliter beaker and placed in heisted now we are going to add three molar naoh and five milliliter increments until the solution becomes strongly basic i calculated that we would need about 20 milliliters of sodium hydroxide because we added 20 milliliters of hcl during our extraction the addition of the sodium hydroxide is being completed on ice because we need

To make sure we keep the temperature below 20 degrees c at all times okay that’s 20 milliliters now let’s go ahead and test the ph using fluent paper and it is strongly basic now that this solution is basic we’ll leave it on ice for a little while longer to have it further crystallize to form our nice solid product now we will use our buechner funnel to vacuum filter

Our product don’t forget to prime the filter with cold distilled water and then check and make sure that the vacuum is intact and we have a seal and then we will load our sample it may involve rinsing out our beaker with a little bit of extra cold distilled water and also may involve scraping with a spatula whatever you have to do to get the most product transferred

And then ultimately to get our product washed with that cold distilled water once you’ve watched it a couple times with cold distilled water maintain the vacuum and let it sit on the filter for a little while to try to make it as dry as possible once dry transfer your product into a pre weighed 50 milliliter beaker while transferring try to get as much product as

Possible without scraping off any parts of the filter paper there you have it there’s your product here’s a map to see how much i’m a product on the day we made it and then the next week i waited again after it had more time to dry to compare set some your sample aside so that we can do a melting point determination an nmr spectra and an ir spectra on your crude

Product last step recrystallization recrystallization is a technique used to purify solid compounds salads tend to be more soluble in hot liquids than in cold liquids so during recrystallization an impure solid compound is dissolved in a hot liquid until the solution is saturated and then the liquid is allowed to cool the compound should then form relatively pure

Crystals ideally any impurities that are present will remain in solution that will not be incorporated into the growing crystals the crystals can be removed from the solution by filtration and subsequent washing with cold solvents please note that not all compound is recoverable some of it will remain in the solution despite it being cold the solvent we were used

To recrystallize lidocaine is hexanes i heated the beaker very gently on a hot plate being careful because hexane has such a low boiling point and is very volatile the laboratory procedure said to add one milliliter of hexane per gram of product however after adding three milliliters of hexane i realized i would need to add more that was clearly a misprint so what

I did was i added hexane slowly until i got all of the product to dissolve once the salad was all dissolved i removed the beaker from the hot plate and placed it in an ice bath to crystallize here is the crystallization process right before your very eyes once everything has crystallized we will transfer to a buechner funnel and remove all the residual solvents

Washing it a few times with cold solvent as well transfer to a weighing boat to get the mass of our final product 4% yield calculations make sure we take a melting point an nmr spectrum and an ir spectrum on this final sample as well and compare these results with the crude product and now safety with jane but subbing in for jane doctor see 50 precautions that we

Have to worry about for this lab all reactions must be done in the fume hood safety glasses and nitrile gloves must be worn at all times glacial acetic acid is highly corrosive to the skin and eyes and because of this must be handled with extreme care to 6 dimethyl lanolin is toxic and readily absorbed through the skin you must wear gloves when handling this and

Any chemical during this experiment alpha floor acetyl chloride is toxic corrosive and is alack mater that means it makes you cry again we must wear gloves diethyl amine is toxic and is very foul-smelling and will therefore be dispensed by your instructor please follow this procedure exactly stay safe there you have it the synthesis of lidocaine where we learn two

New techniques reflux and recrystallization awesome

Transcribed from video
Synthesis of Lidocaine Lab By Amber Charlebois