Manufacture of Local Anesthesia: Cocaine

by: Sol Lim, Anthony Xu, Miguel Zevallos

Introduction:

Cocaine, also known as benzoylmethylecgonine, is a very controversial drug today because although it can  be used as a local anesthetic, usually in optic or nasal surgery, it is actually used primarily as an expensive, addictive, and extremely detrimental illegal substance. It is usually seen as a white powder; typically cocaine is transported as a salt known as cocaine hydrochloride.Cocaine is a powerful nerve stimulant, as referenced in the last post, and is usually associated with euphoria, alertness, and increased energy. However, its side effects include cardiac arrests, myocardial infarctions, hallucinations, hypothermia, and through chronic usage, most likely death.

Origins:

The production of cocaine begins from the leaves of a South American plant known as the Erythroxylon coca, or coca plant. The indigenous peoples of South America have been chewing the leaves of the coca leaf for centuries, as they contain many vital nutrients, as well as several alkaloids, precursors to cocaine. The leaves of the coca plant are consumed by millions of people in the Andes, where it grows, and has no negative side effects. In fact, coca leaves are prescribed to help with altitude sickness, dizziness, and headaches. It is considered a staple crop in the countries surrounding the Andes Mountains and sold in various forms.

However, complete isolations of the cocaine alkaloid from the coca leaves was not achieved until the mid-1850’s by Friedrich Gaedcke. Throughout the late 1800’s, doctors and businessmen alike became interested in both the medicinal and the economic potential of the isolated cocaine molecule. By the early 1900’s, cocaine had become a widespread local anesthetic, and was sold commercially until its prohibition in the later 20th century.

Synthesis of Cocaine:

The illicit synthesis of cocaine involves three primary steps:

  1. Extraction of crude coca paste from the coca leaf

  2. Purification of coca paste to coke base

  3. Conversion of coke base to cocaine hydrochloride.

Extraction: 

The most popular way of producing coca paste is through the solvent extraction technique.

In this process, coca leaves are macerated, dampened, and placed in a maceration pit. Alternately, there is a pre-mixed aqueous solution of the inorganic base which is then poured over the macerated leaves, ensuring that the cocaine is in its free-base form. A water-immiscible organic solvent such as gasoline is later added  to the already dampened coca leaves. This mixture is then either stirred occasionally for the process of 3 days or vigorously mixed, taking only several hours. One of the biggest determinants in the extraction is highly dependant on how fine the leaves were chopped up because this increases the efficiency of the transferring of the cocaine base to the solvent. After the extraction process is complete, the solvent is then removed from the mixture causing the new solution to be mostly organic with the occasional aqueous layer. this new large volume of organic solvent is then back-extracted with a significantly smaller volume of dilute sulfuric acid. This acid is essential because it converts the cocaine-free base into a new substance, that dissolves in the aqueous layer, called cocaine sulfate. The organic solvent then separates, which leaves only the dilute sulfuric acid solution of cocaine sulfate, forming a new solution called “agua rica”. An excess of base is then slowly added to the solution while stirring. This base is responsible for the neutralization of the sulfuric acid, converting the cocaine sulfate back to the free base, which leaves the solution due to its precipitation. This free base, however, precipitates out of the solution in solid form with moldy and yellowish complexion. This is what is known as the coca paste. After this process is done, the coca paste is then dried, filtered, packaged, and is ready to bes sent a lab for the next step.

Purification:

Once the coca paste is made, the next step is to convert this paste to what is known as the coke base through a purification process. The level of cocaine purity once the coca paste is made lies between 30 and 80%. The rest is made up of alkaloidal impurities and inorganic salts that are alter to be removed in order for there to be the highest possible concentration of purified cocaine. The first step in the conversion to the coke base is to redissolve the coca paste in dilute sulfuric acid. The solution formed is then titrated with a fairly concentrated aqueous solution of a powerful oxidizing agent called potassium permanganate.  This potassium permanganate is reduced to manganese dioxide when it reacts with the oxidizable alkaloidal impurities of the coca paste. Once this manganese dioxide is formed in the solution, it quickly proceeds to precipitate out of the solution. The best way to do this reaction is by slowly adding the solution of potassium permanganate to the solution of dissolved coca paste in dilute sulfuric acid and vigorously stirring. The key is to add the exact amount of potassium permanganate so that the final solution is colorless, indicating that the manganese dioxide is fully precipitated out of the solution. If too much potassium permanganate is added, it can cause in decomposition and loss of cocaine, which is the ultimate goal of the entire process. After the solution is complete, it is still acidic and therefore needs to be treated by stirring with a solution of base, for the most part ammonia. The ammonia neutralizes any and all of the remaining sulfuric acid as well as the cocaine sulfate. This final product is called the coke base and is dried, filtered, and packaged.

Conversion:

The final step is known as conversion, where the cocaine base is undergoes several chemical procedures to finally synthesize cocaine hydrochloride in its crystalline form. Unlike the previous steps, cocaine hydrochloride processing is much more dangerous as it requires the use of hazardous, rare chemicals and equipment. In order to convert cocaine base to cocaine hydrochloride, the base is dissolved into diethyl ether to create a solution, allowing the extraction of any impurities or undesirable material from the solution through filtration.  Next, hydrochloric acid is diluted in acetone and the resulting solution is mixed with the cocaine solution. The presence of hydrochloric acid allows ion-pairs to be formed with the cocaine base, precipitating cocaine hydrochloride out of the mixed solution as shiny white, flaky crystals. This precipitation process usually takes between 3 to 6 hours to fully complete the crystallization process. However, if time is limited, the rate of ion-pair reaction can be accelerated by placing the solution in a hot water bath called a “bańo maria”. Though the total reaction time is reduced to a favorable 30 minutes, the use of this technique has been reported to demean the quality of cocaine hydrochloride. After crystallization, the cocaine hydrochloride is then dried using heat lamps or microwaves and prepared for distribution.  Illicitly synthesized cocaine hydrochloride usually ranges 80%-97% purity, with many alkaloidal impurities (present in the coke base) appearing in the final product.

Bańo maria pictured above

Especially in South America, the acquiring of the solvents used in this step (diethyl ether and acetone) is difficult therefore manufacturers resort to alternatives that will be an adequate substitution. When choosing the alternatives, the manufacturers must keep three concepts in mind in order to successfully synthesize cocaine hydrochloride:

1.       Solubility of coke base in diethyl ether alternative

2.       Miscibility of acetone alternative with hydrochloric acid

3.       Insolubility of cocaine hydrochloride in combined solvent mixture (diethyl ether alternative + acetone alternative)

The most common substitutes for the solvents include methyl ethyl ketone, ethyl acetate, toluene, and so forth.

Crack Cocaine:

               A rising, popular trend in modern society is to convert cocaine hydrochloride into crack cocaine: a more potent form of cocaine has been recorded to induce a very intense high within a matter of seconds. Though the response is immediate making it addictive, it is short lived and followed by an intense period of depression and desire for more. Common impurities within crack also release toxic fumes when combusted therefore posing a health risk to using crack cocaine. Opposed to powder cocaine hydrochloride, crack cocaine vaporizes (90o C) at a much lower temperature therefore allowing it to be inhaled and triggering an immediate response by the body to its effects. The cause for this change in melting point is a result of how crack cocaine is produced. Crack cocaine is synthesized by dissolving cocaine hydrochloride in a mixture of water and baking soda and heating the solution until all the hydrochloride is removed. The remaining product is a waxy substance that hardens when dried: crack cocaine.  The color generally ranges from white to a yellowish cream to a light brown.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s