The Chemistry of Hydrocodone

Introduction

Hydrocodone is a prescription drug which is used to treat moderate to severe aches and pains and to suppress coughing. I chose to research the chemistry of Hydrocodone because the drug has personally affected my life. I have been prescribed Hydrocodone twice, for breaking my leg and my hand. It helped me to bear the pain of my injuries, so I wanted to learn more on how the drug is made and how it acts on my body.

Composition of ...

    • Codeine
      • Opiate used to treat pain and cough
      • Molar Mass: 299.364 g/mol
      • C18H21NO3
    • Diimide
      • Yellow gas
      • Molar Mass: 30.03 g·mol−1
      • H2N2
    • Thebaine
    • Sulfonic Acid Hydrazide (p-toluenesulfonyl hydrazide)
      • CH3C6H4SO2NHNH2
      • Strong acid
      • Crystalline solid
    • Ethanolamine
    • Alkoxy alkanol (2-methoxyethanol)
      • Organic compound mainly used as a solvent
      • clear, colorless liquid with an ether-like odor
      • It has the ability to dissolve a variety of different types of chemical compounds and is very miscible
      • C3H8O2

Main Chemicals, Compounds, Components

    • Codeine (C18H21NO3)

Codeine is an opiate alkaloid found in the opium poppy. It is used to treat pain and suppress coughs. Codeine has been used in the past as the starting material and base of many mild to moderately strong opioids; such as Hydrocodone. It is one of the main compounds that can be synthesized into Hydrocodone.

    • Diimide (H2N2)

Diimide (also known as Diazene) is a yellow gas mainly used in chemical reactions to convert unsaturated organic compounds to reduced alkane products. In the process, diimide is oxidized to dinitrogen. Diimide is usually synthesized from hydrazine.

    • Thebaine (C19H21NO3)

Thebaine is an opiate alkaloid that is very chemically similar to codeine, but has stimulatory rather than depressant effects. Thebaine is the other main compound that is synthesized into Hydrocodone through various chemical processes. It comes from the opium poppy (mainly the Iranian Poppy) and is used to convert into other drugs.

    • Sulfonic Acid Hydrazide (p-toluenesulfonyl hydrazide) CH3C6H4SO2NHNH2

P-toluenesulfonyl hydrazide is a sulfonic acid, that is in the form of a crystalline solid. It is composed of Carbon, Hydrogen, Nitrogen, Oxygen, and Sulfur.

    • Ethanolamine (HOCH2CH2NH2)

Ethanolamine is an organic base that is produced by reacting ethylene oxide with aqueous ammonia. It is a colorless, viscous liquid with an odor reminiscent to that of ammonia. Ethanolamine is the second most abundant head group for phospholipids. It is most commonly used in production of detergents, polishes, and pharmaceuticals.

    • Alkoxy alkanol (2-methoxyethanol) C3H8O2

2-methoxyethanol is part of the alkoxy alkanol group and it is mostly used as a solvent. The organic compound is clear, colorless liquid, with an ether like odor. It is notable for its ability to dissolve a variety of different types of chemical compounds and for its miscibility with water, which is helpful in synthesizing Hydrocodone.

Chemistry's Role

Hydrocodone solely exists due to chemistry. Hydrocodone is semi-synthesized from the opioids codeine and thebaine. Currently, the most efficient way to synthesize Hydrocodone is through Thebaine; however, the traditional way of synthesizing the drug was through codeine. The first way to make Hydrocodone is through Diimide reduction, however it is not as cost efficient and pure as the more modern methods. Modern Hydrocodone is usually derived from Thebaine. To produce Hydrocodone you first need to chemically change Thebaine into 8,14-dihydro thebaine. This can be achieved through the older method of Diimide reduction, which is a chemical reactions that convert unsaturated organic compounds to reduced alkane products. As that reaction occurs, Diimide, which is composed of nitrogen and hydrogen, is oxidized to dinitrogen at a rate which can be hazardous. So now the way to turn Thebaine into 8,14-dihydro thebaine involves a few complex steps. To control the rate of the Diimide reaction, there is an addition of a hydrazide solution and the maintaining of the reaction temperature. Also there is no need of aqueous basification which renders the drug more pure. First, Thebaine is partially dissolved in an alkoxy solvent, preferably 2-methoxyethanol, to form a Thebaine mixture. Thermal screening has shown that the sulfonic acid p-toluenesulfonyl hydrazide decomposes to form Diimide at a high temperature. When the acid is heated in the presence of ethanolamine, this decomposition begins at a lower temperature. So the acid is heated at a constant temperature of 75° C. The heated p-toluenesulfonyl hydrazide, is then dissolved into an organic base to form a hydrazide base solution. The base, which is preferably Ethanolamine, is to be at a ratio of 12 times the amount of thebaine in the mixture. Finally, the hydrazide base solution is combined with the thebaine mixture to form a reaction mixture that is cooled to precipitate 8,14-dihydro thebaine. The yield of Hydrocodone that is produced when the 8,14-dihydro thebaine precipitates, is expected to be of 97-99% purity. All in all Hydrocodone is made through chemical reactions and synthesis; so, it exists due to chemistry. Chemistry truly is involved in everything around, such as the medicines and drugs that keep us healthy. Chemistry really is life.

Background Research

Injuries are unavoidable in life; they are bound to happen sometime or another, but how do we reduce pain and make people more comfortable? One major solution is the prescription drug Hydrocodone. Hydrocodone is used to treat moderate to severe aches and pains and to suppress coughing. While Hydrocodone is very similar to the drugs Codeine and Thebaine, which it is synthesized from, this narcotic analgesic is equivalent to the strength of highly potent euphoric drugs, such as: oxycodone, heroin, and morphine. This drug is a semi-synthesized opioid, synthesized from codeine or thebaine, which are opioid alkaloids found in the opium poppy. In simple terms Hydrocodone is made from chemical synthesis of Codeine and Thebaine; which is made from the naturally occurring resource the opium poppy. Hydrocodone works by affecting the opioid system in the brain. The opioid system controls pain, reward, and addictive behaviors. Opioids, such as Hydrocodone, attach to opioid receptors and reduce the perception of pain. However, Hydrocodone can be highly addictive as some people experience a sense of euphoria while taking the drug due to the opioid system, which Hydrocodone effects, being the center of reward. Still, Hydrocodone is one of the most widely prescribed drugs in the United States; having over 100 million prescriptions given in 2010 alone! Since pure Hydrocodone is so powerful to the brain, it is a Schedule II controlled substance; so most of the time Hydrocodone is mixed with one or more drugs such as acetaminophen, ibuprofen, aspirin, and antihistamines. The drug was first synthesized by two German chemists named Carl Mannich and Helene Lowenheim in 1920; however, the FDA finally gave approval to the drug in 1943 for use and production in the U.S.

Resources

https://en.wikipedia.org/wiki/Hydrocodone

    • What is Hydrocodone, uses
    • Medical Uses
    • Side Effects
    • Pharmacology
    • Formulas of Hydrocodone
    • Brief History

https://www.drugs.com/hydrocodone.html

    • Overview:
      • What is Hydrocodone
      • How and Why to take Hydrocodone
      • Dangers of the Drug
    • Side Effects
    • Dosage
    • Interactions
    • How it works

http://drugabuse.com/library/the-effects-of-hydrocodone-use/

    • The Effects of Hydrocodone Use

https://en.wikipedia.org/wiki/Opioid

    • What are Opioids

https://en.wikipedia.org/wiki/Papaver_somniferum

    • Basic information of the Opium Poppy plant

https://en.wikipedia.org/wiki/Dopamine

    • What is Dopamine
    • Dopamine and the brain

https://www.naabt.org/faq_answers.cfm?ID=6

    • How Opioids work in the brain
    • Purpose of Opioid Receptors

http://www.mydr.com.au/pain/pain-and-how-you-sense-it

    • What is pain
    • How do you sense pain

https://www.eurekalert.org/pub_releases/2007-10/econ-hdt101207.php

    • How does the opioid system work

http://aforeverrecovery.com/drug-rehabilitation/painkiller/the-history-of-hydrocodone/

    • History of Hydrocodone
      • Origin
      • Use in the US

https://pubchem.ncbi.nlm.nih.gov/compound/hydrocodone#section=Solubility

    • The basic chemistry of Hydrocodone

https://www.google.com/patents/US9273060?dq=hydrocodone&hl=en&sa=X&ved=0ahUKEwiUoMKWjoHRAhWFllQKHXkqA0gQ6AEIIzAB

    • Description of how Hydrocodone is made.

https://en.wikipedia.org/wiki/2-Methoxyethanol

    • Basic information of 2-Methoxyethanol

https://en.wikipedia.org/wiki/Diazene

    • Basic information on Diimide

https://en.wikipedia.org/wiki/Thebaine

    • Basic information of Thebaine

https://en.wikipedia.org/wiki/Hydrazide

    • Basic information on p-Toluenesulfonyl Hydrazide

About the Author

Ben LaBeau is a junior at Billings Senior High School. He is in the Platinum Program and is an Honor Roll Student at Senior High. He participates in football and basketball, and recently won the Montana AA State Football Championship with his team as a starter. He became interested in the Hydrocodone after he was prescribed it twice, when he broke his leg and hand. He enjoyed learning about how chemistry played a role in developing hydrocodone, which was a need in his life during times of injury.