2C-i and it’s effects

2C-I, also known as 2,5-dimethoxy-4-iodophenethylamine, is a phenethylamine of the 2C family with psychedelic effects. It was first synthesized by Alexander Shulgin and described in his book PiHKAL (1991). Its chemical structure is 4-iodo-2,5-dimethoxyphenethylamine, with the molecular formula C10H14INO2 and a molecular weight of 307.13 g/mol. Below is information regarding the synthesis of 2C-I and its precursors:

Synthesis Complexity

• Iodination Reaction: The iodination of the aromatic ring is a key step in 2C-I synthesis. In the synthesis of 2C-I metabolites, iodination of the aromatic ring can be successfully carried out using iodine and orthoperiodic acid as iodinating reagents. However, iodination reactions require precise control of reaction conditions such as temperature, time, and the ratio of reagents to achieve selective iodination. Improper conditions may lead to side reactions or difficulty in controlling the position of iodine substitution.
• Deprotection Reaction: The selective deprotection of aryl benzyl ethers is another important step. Acid hydrolysis using trifluoroacetic acid and thioanisole can achieve this, but the reaction conditions must be carefully optimized to avoid damaging other parts of the molecule or causing unwanted side reactions.
• Overall Synthesis Difficulty: The synthesis of 2C-I involves multiple steps, including iodination and deprotection, requiring proficiency in organic chemistry synthesis techniques and familiarity with reaction conditions and operational methods. It also demands access to specialized equipment and materials. Generally, it is not overly complex for professional chemists but still poses a certain level of challenge. Additionally, the synthesis process may involve some safety risks, such as the toxicity and corrosiveness of iodine and other reagents.

Precursors and Legal Sources

• 2,5-Dimethoxyphenethylamine: This is a key precursor in the synthesis of 2C-I. However, its production and use are subject to strict regulatory controls. In the United States, it is classified as a Schedule I controlled substance. In many other countries, it is also subject to stringent regulation. Unauthorized production or possession may constitute a violation of the law.
• Iodine and Periodic Acid: Iodine and periodic acid are commonly used iodinating reagents. Iodine is a common chemical, but its purchase and use may be restricted in certain regions. Periodic acid is primarily used as a reagent in laboratories and is typically subject to regulatory oversight. Purchasing and using it may require proper licensing and compliance with relevant regulations.
• Trifluoroacetic Acid and Thioanisole: These are commonly used organic reagents in laboratories. Trifluoroacetic acid is a strong acid with strong corrosivity and toxicity. Thioanisole is also a toxic chemical. Their purchase and use are subject to certain restrictions. In some regions, they may be classified as hazardous chemicals, and their procurement and storage must adhere to strict safety regulations.

Legal Status and Risks

• Controlled Substance: 2C-I is classified as a Schedule I controlled substance in the United States and is prohibited in many other countries. Its production, sale, and possession are illegal. Engaging in its synthesis may lead to severe legal consequences.
• Safety Risks: 2C-I itself has hallucinogenic effects and poses potential risks to human health. Overuse or misuse may result in adverse effects such as psychosis, cardiovascular issues, and respiratory problems. Additionally, the synthesis process involves hazardous chemicals and reactions, posing safety risks to the operators and the surrounding environment.

In summary, while the synthesis of 2C-I is not extremely complex, it requires a certain level of expertise and knowledge in organic chemistry. More importantly, the precursors involved are subject to strict regulatory controls, and its synthesis and use are illegal. For research purposes, it is essential to adhere to legal regulations and ethical norms, conduct research within a legal framework, and prioritize safety. Below is the synthesis method described by Alexander Shulgin in PiHKAL: Iodine was used to iodinate 2,5-dimethoxyphenethylamine, followed by a series of reactions to obtain 2C-I. However, its synthesis and use are strictly prohibited in most countries. The information provided here is for research purposes only.

According to the U.S. Drug Enforcement Administration (DEA), 2C-I is typically consumed orally or nasally in powder form. It is metabolized by the monoamine oxidase (MAO) enzymes MAO-A and MAO-B. Monoamine oxidase inhibitors (MAOIs), such as phenelzine, tranylcypromine, moclobemide, and selegiline, may enhance the effects of 2C-I, potentially leading to overdose and serious toxicity. In forensic analysis, 2C-I can undergo O-demethylation, N-acetylation, and deamination, followed by oxidation to the corresponding carboxylic acid in rats. The following is a synthesis and identification study of urinary metabolites of 4-iodo-2,5-dimethoxyphenethylamine (2C-I) published in the Journal of Forensic Sciences in 2011: 2C-I hydrochloride was administered orally to male Sprague-Dawley rats. Urinary extracts were analyzed using gas chromatography/mass spectrometry (GC/MS), and five potential 2C-I metabolites were synthesized in the laboratory. During the synthesis of 2C-I metabolites, iodination of the aromatic ring was successfully performed using iodine and orthoperiodic acid as iodinating reagents. Selective deprotection of aryl benzyl ethers was achieved through acid hydrolysis using trifluoroacetic acid and thioanisole. The synthesized metabolites were well separated and detected by GC/MS after valeryl derivatization.

The 2C family of compounds, including 2C-I, was first synthesized by Alexander Shulgin. In his book PiHKAL, he detailed the synthesis of over 200 psychedelic compounds, including 2C-I. After the publication of Shulgin’s book, the use of 2C compounds increased in popularity. In 2004, Shulgin’s book PiHKAL was cited in a study titled “Synthesis and Identification of Urinary Metabolites of 4-Iodo-2,5-Dimethoxyphenethylamine” published in Forensic Science International. The study described the synthesis of 2C-I and its metabolites. In 2015, a study titled “2C-I-NBOMe, an ‘N-bomb’ that kills with ‘Smiles’: Toxicological and legislative aspects” highlighted the toxicological and legal implications of 2C-I-NBOMe, an NBOMe derivative of 2C-I. In 2019, a study titled “Mechanisms Behind the Neurotoxicity of 2C-I and 25I-NBOMe” explored the neurotoxicity mechanisms of 2C-I and its NBOMe derivative. In 2021, a study titled “Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore” analyzed the structure-activity relationship of psychedelics, including 2C-I, in a rat asthma model.

In some countries, the legal status of 2C-I varies. For example, in Australia, it is classified as a Schedule 9 prohibited substance; in Brazil, it falls under Class F2 of prohibited psychotropics; in Canada, it is listed under Schedule III; in the UK, it is a Class A controlled substance; and in the US, it is a Schedule I controlled substance. In China, 2C-I is classified as a first-class psychotropic substance. According to the Regulations on the Administration of Narcotic Drugs and Psychotropic Substances, the production, operation, and use of 2C-I are subject to strict control. Unauthorized production, operation, or use is illegal and may result in criminal liability.